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Takahiko Yoshimoto, Hiroki Sakurai, Yusuke Ohmichi, Mika Ohmichi, Atsuko Morimoto, Takahiro Ushida, Jun Sato
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245544

Abstract:
To elucidate the relationship between chronic pain conditions with cast immobilization and autonomic function, we investigated the functional changes of the autonomic nervous system in conscious rats with chronic post-cast pain (CPCP) induced by a two-week cast immobilization of one hind limb. We telemetrically examined the time courses of systolic arterial blood pressure (SBP), heart rate (HR), and the middle-frequency (MF) component obtained from the power spectral analysis of SBP variability as a vasomotor sympathetic index. We also investigated the baroreflex sensitivity to phentolamine, an α-adrenoceptor antagonist, and the SBP and HR responses to a low ambient temperature (LT; 9.0 ± 0.2°C) exposure, a sympathetic stimulant. Rats exposed to cast immobilization exhibited mechanical allodynia lasting for at least 10 weeks after cast removal in the calf area (skin and muscle) of the bilateral hind limbs. Under resting conditions, the SBP, HR, and MF components were significantly increased during cast immobilization (all p < 0.001). Following cast removal, these parameters gradually decreased and within 1 week reached lower than baseline levels, lasting for over 10 weeks. Phentolamine administration (10 mg/kg, intraperitoneally) significantly decreased the SBP before and during cast immobilization (before, p < 0.001; during, p = 0.001) but did not lower the SBP after cast removal. The baroreflex gain after phentolamine administration, calculated as the HR increase divided by the SBP reduction, was significantly increased after cast removal (p = 0.002). The SBP increase on LT exposure was significantly greater after cast removal than that before cast immobilization, suggesting hypersensitivity to sympathetic neurotransmitters. These results revealed that, in the CPCP model, sympathetic activation was augmented during cast immobilization, which then decreased after cast removal and remained below normal levels with persisting pain behaviors. Additionally, the responsiveness of the autonomic nervous system was impaired in the CPCP model.
Virginia Matzek , Kerrie A. Wilson
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245074

Abstract:
The ecosystem services concept has come into wide use in conservation and natural resource management, partly due to its appeal as an anthropocentric rationale for protecting and restoring nature. Proponents of the ecosystem services concept expect that presenting these arguments alongside biodiversity arguments should lead to a broader base of support for conservation. This raises the question of whether support for activities that ensure ecosystem service provision relates to different sets of core values, or environmental attitudes, than support for biodiversity protection. We surveyed adult Australians to evaluate the influence of values and attitudes on willingness to pay for different habitat restoration outcomes. We hypothesized that when restoration is framed with an anthropocentric rationale (such as ecosystem service provision), support for restoration would align more strongly with anthropocentric or self-centered values and attitudes. Specifically, we tested if preference for ecosystem service benefits over biodiversity attributes, as indicated by willingness to pay in different restoration scenarios, is more strongly associated with self-enhancing (Egoistic) than self-transcending (Altruistic and Biospheric) values, and more associated with a pro-use attitude towards nature (Utilization) than an anti-use attitude (Preservation). We found that support for habitat restoration is generally based on ecocentric values and attitudes, but that positive associations between pro-environmental behavior and Egoistic values emerge when emphasis is placed on ecosystem service outcomes. Individuals scoring higher on Egoistic/Utilization metrics were also more likely to anticipate disservices from restoration. Attitudes predicted behavioral intention (willingness to pay) better than core values. Our results support the notion that the ecosystem services concept garners nontraditional backers and broadens the appeal of ecological restoration.
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245618

Abstract:
Skeletal muscle gene expression is governed by the myogenic regulatory family (MRF) which includes MyoD (MYOD1) and myogenin (MYOG). MYOD1 and MYOG are known to regulate an overlapping set of muscle genes, but MYOD1 cannot compensate for the absence of MYOG in vivo. In vitro, late muscle genes have been shown to be bound by both factors, but require MYOG for activation. The molecular basis for this requirement was unclear. We show here that MYOG is required for the recruitment of TBP and RNAPII to muscle gene promoters, indicating that MYOG is essential in assembling the transcription machinery. Genes regulated by MYOD1 and MYOG include genes required for muscle fusion, myomaker and myomerger, and we show that myomaker is fully dependent on activation by MYOG. We also sought to determine the role of MYOD1 in MYOG dependent gene activation and unexpectedly found that MYOG is required to maintain Myod1 expression. However, we also found that exogenous MYOD1 was unable to compensate for the loss of Myog and activate muscle gene expression. Thus, our results show that MYOD1 and MYOG act in a feed forward loop to maintain each other’s expression and also show that it is MYOG, and not MYOD1, that is required to load TBP and activate gene expression on late muscle gene promoters bound by both factors.
Bruno Kluwe-Schiavon, Thiago Wendt Viola, Lucas Poitevin Bandinelli, Sayra Catalina Coral Castro, Christian Haag Kristensen, Jaderson Costa Da Costa, Rodrigo Grassi-Oliveira
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245261

Abstract:
We investigated what degree of risk of infection with COVID-19 is necessary so that people intend to stay home, even when doing so means losing their salary. We conducted an online survey across Brazil during the initial outbreak, in which 8,345 participants answered a questionnaire designed to identify the maximum tolerated risk (k’) necessary for them to disregard social distancing recommendations and guarantee their salaries. Generalized linear mixed models, path analysis structural equation, and conditional interference classification tree were performed to further understand how sociodemographic factors impact k’ and to establish a predictive model for the risk behavior of leaving home during the pandemic. We found that, on average, people tolerate 38% risk of infection to leave home and earn a full salary, but this number decreased to 13% when the individual risk perception of becoming ill from severe acute respiratory syndrome coronavirus-2 is considered. Furthermore, participants who have a medium-to-high household income and who are older than 35 years are more likely to be part of the risk-taking group who leave home regardless of the potential COVID-19 infection level; while participants over 45 years old and with good financial health are more likely to be part of the risk-averse group, who stay home at the expense of any salary offered. Our findings add to the political and public debate concerning lockdown strategies by showing that, contrary to supposition, people with low socioeconomic status are not more likely to ignore social distancing recommendations due to personal economic matters.
Helena Puszka, Jeff Shimeta, Kate Robb
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0243353

Abstract:
Vessels cause considerable disturbance to cetaceans world-wide, with potential long-term impacts to population viability. Here we present a comprehensive review of vessel impacts to cetacean behavior in Australian waters (2003–2015), finding inadequate protections to be in place. The majority of these studies found trends of decreased animal travel and resting behavioral states as well as low compliance to regulations, and they recommended further regulatory action such as greater enforcement or monitoring, or passive management strategies. As a case study, we conducted the first field assessment of vessel compliance with the Wildlife (Marine Mammal) Regulations 2009 in Gippsland Lakes, Australia, and provide the first assessment of the endangered Gippsland Lakes Burrunan dolphin (Tursiops australis) population’s behavioral ecology. Dolphin behavior and vessel regulation compliance data were collected during boat-based surveys of Gippsland Lakes from July 2017 to January 2018, with a total of 22 dolphin group sightings resulting in 477 five-minute point samples. 77% of dolphin sightings involved vessel interactions (within 400 m), and 56 regulation breaches were observed. These breaches were most severe in summer (mean = 4.54 breaches/hour). Vessels were found to alter dolphin behavior before, during, and after interactions and regulation breaches, including increased mating (mate guarding) and milling behavioral states, and increased ‘fish catch’, ‘high leap’ and ‘tail slap’ behavioral events. These behavioral changes may indicate masking of the dolphins' acoustic communication, disturbance of prey, increased dolphin transition behaviors, and/or induced stress and changes to group structure (including increased mate guarding). While our results provide evidence of short-term altered behavior, the potential for long-term effects on population dynamics for this threatened species is high. In the context of reported inadequate cetacean protection Australia-wide, our management recommendations include greater monitoring and enforcement, and the utilisation of adaptive management.
Marika Premoli , Daniele Baggi, Marco Bianchetti, Alessandro Gnutti, Marco Bondaschi, Andrea Mastinu, Pierangelo Migliorati, Alberto Signoroni , Riccardo Leonardi, Maurizio Memo, et al.
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0244636

Abstract:
Ultrasonic vocalizations (USVs) analysis is a well-recognized tool to investigate animal communication. It can be used for behavioral phenotyping of murine models of different disorders. The USVs are usually recorded with a microphone sensitive to ultrasound frequencies and they are analyzed by specific software. Different calls typologies exist, and each ultrasonic call can be manually classified, but the qualitative analysis is highly time-consuming. Considering this framework, in this work we proposed and evaluated a set of supervised learning methods for automatic USVs classification. This could represent a sustainable procedure to deeply analyze the ultrasonic communication, other than a standardized analysis. We used manually built datasets obtained by segmenting the USVs audio tracks analyzed with the Avisoft software, and then by labelling each of them into 10 representative classes. For the automatic classification task, we designed a Convolutional Neural Network that was trained receiving as input the spectrogram images associated to the segmented audio files. In addition, we also tested some other supervised learning algorithms, such as Support Vector Machine, Random Forest and Multilayer Perceptrons, exploiting informative numerical features extracted from the spectrograms. The performance showed how considering the whole time/frequency information of the spectrogram leads to significantly higher performance than considering a subset of numerical features. In the authors’ opinion, the experimental results may represent a valuable benchmark for future work in this research field.
Catiule De Oliveira Santos, Sidnei Ferro Costa, Fabiana Santana Souza, Jessica Mariane Ferreira Mendes, Cristiane Garboggini Melo De Pinheiro, Diogo Rodrigo De Magalhães Moreira , Luciano Kalabric Silva, Valeria Marçal Felix De Lima, Geraldo Gileno De Sá Oliveira
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0239171

Abstract:
RIL-10 plays a major role in restricting exaggerated inflammatory and immune responses, thus preventing tissue damage. However, the restriction of inflammatory and immune responses by IL-10 can also favor the development and/or persistence of chronic infections or neoplasms. Dogs that succumb to canine leishmaniasis (CanL) caused by L. infantum develop exhaustion of T lymphocytes and are unable to mount appropriate cellular immune responses to control the infection. These animals fail to mount specific lymphoproliferative responses and produce interferon gamma and TNF-alpha that would activate macrophages and promote destruction of intracellular parasites. Blocking IL-10 signaling may contribute to the treatment of CanL. In order to obtain a tool for this blockage, the present work endeavored to identify the canine casIL-10R1 amino acid sequence, generate a recombinant baculovirus chromosome encoding this molecule, which was expressed in insect cells and subsequently purified to obtain rcasIL-10R1. In addition, rcasIL-10R1 was able to bind to homologous IL-10 and block IL-10 signaling pathway, as well as to promote lymphoproliferation in dogs with leishmaniasis caused by L. infantum.
Shunsuke Kimura, Masahiro Sekiguchi, Kentaro Watanabe, Mitsuteru Hiwatarai, Masafumi Seki, Kenichi Yoshida, Tomoya Isobe, Yusuke Shiozawa, Hiromichi Suzuki, Noriko Hoshino, et al.
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245526

Abstract:
Neuroblastoma, the most common extracranial solid malignancy among children, originates from undifferentiated neural crest cells (NCC). Despite recent intensified treatment, high-risk patients still have a high mortality rate. To explore a new therapeutic strategy, we performed an integrated genomic and transcriptomic analysis of 30 high-risk neuroblastoma cases. Based on the expression profiling of RNA sequencing, neuroblastoma was classified into Mesenchymal (MES; n = 5) and Noradrenergic (ADRN; n = 25) clusters, as previously reported in the super-enhancer landscape. The expression patterns in MES-cluster cases were similar to normal adrenal glands, with enrichment in secretion-related pathways, suggesting chromaffin cell-like features built from NCC-derived Schwann cell precursors (SCPs). In contrast, neuron-related pathways were enriched in the ADRN-cluster, indicating sympathoblast features reported to originate from NCC but not via SCPs. Thus, MES- and ADRN-clusters were assumed to be corresponding to differentiation pathways through SCP and sympathoblast, respectively. ADRN-cluster cases were further classified into MYCN- and ATRX-clusters, characterized by genetic alterations, MYCN amplifications and ATRX alterations, respectively. MYCN-cluster cases showed high expression of ALDH18A1, encoding P5CS related to proline production. As reported in other cancers, this might cause reprogramming of proline metabolism leading to tumor specific proline vulnerability candidate for a target therapy of metabolic pathway. In ATRX-cluster, SLC18A2 (VMAT2), an enzyme known to prevent cell toxicity due to the oxidation of dopamine, was highly expressed and VMAT2 inhibitor (GZ-793A) represented significant attenuation of cell growth in NB-69 cell line (high SLC18A2 expression, no MYCN amplification) but not in IMR-32 cell line (MYCN amplification). In addition, the correlation of VMAT2 expression with metaiodobenzylguanidine (MIBG) avidity suggested a combination of VMAT2 inhibitor and MIBG radiation for a novel potential therapeutic strategy in ATRX-cluster cases. Thus, targeting the characteristics of unique neuroblastomas may prospectively improve prognosis.
Santosh K. Ojha , Luben D. Dimov , Wubishet Tadesse
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245218

Abstract:
The long-term decline of longleaf pine-dominated forests has received considerable attention among land managers and conservation professionals in the last few decades. The objective of this study was to investigate the change in and the variation of the proportion, density, growth, and dominance of longleaf pine across the longleaf pine ecosystems for the 1997–2018 period. We used two sets of measurements of 1,432 plots from the Forest Inventory and Analysis (FIA) dataset covering the entire current longleaf pine range. The relationship between disturbances and longleaf pine basal area ratio and basal area growth were analyzed using linear mixed modeling. Change detection maps were produced using the Inverse Distance Weighted (IDW) interpolation method. The total basal area and aboveground biomass per hectare increased in 64% and 72%, but decreased in 30% and 28% of the study area, respectively, between the first and last inventory intervals. Species richness and diversity generally decreased across the studied plots. Longleaf pine tree density and importance value percent increased during the period. However, longleaf basal area ratio and aboveground biomass ratio in the stands decreased on average by 5% during the period, although these ratios increased in some locations in southwest Georgia and near the west coast of Florida. The longleaf pine basal area ratio and aboveground biomass ratio decreased equally in 37%, and increased in 19% and 21% of the study area, respectively. There was about 79% variation in the ratio of longleaf pine basal area among plots. When compared to the natural control of no disturbance, fire disturbance was significantly associated with greater longleaf pine basal area ratio and basal area growth. Understanding the change in growth and distribution patterns of longleaf pine across its range over time is vital to restore these critical ecosystems.
Jianjia He , Xiumeng Wu, Junxiang Li, Shengxue He
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245622

Abstract:
The multi-energy conversion system (MCS) plays an important role in improving the utilization of energy resources and realizing the energy transition. With the application of the new generation of information technologies, the new MCS can realize real-time information interaction, multi-energy collaboration, and real-time demand response, in which energy suppliers can intelligently motivate consumers' energy use behavior. In this paper, an MCS coupled with a cloud platform is proposed to address information explosion and data security issues. Due to the development of Internet technology, the increasing energy data, and the serious energy coupling, it is difficult for traditional optimization methods to deal with the interaction between participants of the MCS. Therefore, the non-cooperative game is used to formulate the interactions between participants with the aim of maximizing the energy suppliers' profit and minimizing the customers' cost. It is proved that the game model is an ordinary game with one Nash equilibrium. The simulation was performed with a gradient projection algorithm and the results show that the proposed MCS improves energy utilization efficiency through energy conversion while ensuring consumer satisfaction, and benefits both the customers and suppliers by reducing the energy consumption cost and the peak load demand, which effectively improve the supply quality and enrich the energy consumption patterns.
Yu Wang, Jialu Qiao, Dandan Zhang, Chunyan Zhong, Shengya Wang, Xiaomei Li, Lingyan Feng, Shen Shi, Bingxue Wang, Qingzhen Liu
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245694

Abstract:
Autophagy is a conserved cellular process playing a role in maintenance of cellular homeostasis and response to changing nutrient conditions via degradation and recirculation of cellular redundant components. Autophagy-related proteins (Atg) play important function in autophagy pathway. Aedes albopictus mosquito is an effective vector transmitting multiple viruses which cause serious human diseases. Moreover, Aedes albopictus mosquito is becoming a serious threat to human health due to its widening distribution in recent years and thus worth of more research attention. It was reported that autophagy might play a role in viral infection in Aedes mosquito. To better understand the interaction between autophagy and arbovirus infection in mosquito system, it is necessary to identify autophagy pathway in the system. However, autophagy in Aedes albopictus mosquito is still poorly understood so far. We recently identified AaAtg8, the first Atg protein reported in Aedes albopictus mosquito. This work further identified twelve atg genes in Aedes albopictus mosquito. Sequence and phylogenetic analysis of the twelve atg genes were performed. Expression profiles of all the twelve Aaatg genes in different developmental stages and genders of Aedes albopictus mosquito were conducted. Effects of chemicals inhibiting or inducing autophagy on the levels of eight identified AaAtg proteins were examined. The function of two identified AaAtg proteins AaAtg6 and AaAtg16 and their response to arbovirus SINV infection were studied preliminarily. Taken together, this work systematically identified Aedes albopictus atg genes and provided basic information which might help to elucidate the autophagy pathway and the role of autophagy in arbovirus infection in Aedes mosquito system.
Mohammed Faruk, Sani Ibrahim, Surajo Mohammed Aminu, Ahmed Adamu, Adamu Abdullahi, Aishatu Maude Suleiman, Abdulmumini Hassan Rafindadi, Abdullahi Mohammed, Yawale Iliyasu, John Idoko, et al.
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245581

Abstract:
Evasion of apoptosis is associated with treatment resistance and metastasis in colorectal cancer (CRC). Various cellular processes are associated with evasion of apoptosis. These include overexpression of pro-apoptotic proteins (including p53 and PD-L1), anti-apoptotic proteins (BIRC7/Livin and Bcl-2), chemokine receptors (including DARC), and dysregulation of DNA mismatch repair proteins (including MSH2 and PMS2). The aim of this study was to determine the effect of folinic acid, 5-FU and oxaliplatin (FOLFOX) as a single agent and aspirin plus FOLFOX in various combinations on the aforementioned proteins in human CRC, SW480 cell line and rat models of N-Methyl-N-Nitrosourea (NMU)-induced CRC. In addition, effects of the NMU-induced CRC and chemotherapeutic regimens on haematological and biochemical parameters in the rat models were studied. Immunohistochemistry, immunofluorescence and immunoblot techniques were used to study the expression pattern of the related proteins in the human CRC cells pre- and post-treatment. Double contrast barium enema, post-mortem examination and histological analyses were used to confirm tumour growth and the effect of the treatment in vivo in rat models. Notably, we found in human mucinous CRC, a significant increase in expression of the BIRC7/Livin post-FOLFOX treatment compared with pre-treatment (p = 0.0001). This increase provides new insights into the prognostic role of BIRC7/Livin in evasion of apoptosis and facilitation of treatment resistance, local recurrence and metastasis particularly among mucinous CRCs post-FOLFOX chemotherapy. These poor prognostic features in the CRC may be further compounded by the significant suppression of DARC, PD-L1, PMS2 and overexpression of MSH2 and anti-apoptotic Bcl-2 and p53 proteins observed in our study (p < 0.05). Importantly, we found a significant reduction in expression of BIRC7/Livin and reactivation of DARC and PD-L1 with a surge in Annexin V expression in rat models of CRC cells post-treatment with a sequential dose of aspirin plus FOLFOX compared with other treatments in vivo (p
Shujian Liao, Chenbo Yang, Dengao Li
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245561

Abstract:
Precision point positioning (PPP) is widely used in maritime navigation and other scenarios because it does not require a reference station. In PPP, the satellite clock bias (SCB) cannot be eliminated by differential, thus leading to an increase in positioning error. The prediction accuracy of SCB has become one of the key factors restricting positioning accuracy. Although International GNSS Service (IGS) provides the ultra-rapid ephemeris prediction part (IGU-P), its quality and real-time performance can not meet the practical application. In order to improve the accuracy of PPP, this paper proposes to use the Prophet model to predict SCB. Specifically, SCB sequence is read from the observation part in the ultra-rapid ephemeris (IGU-O) released by IGS. Next, the SCB sequence between adjacent epochs are subtracted to obtain the corresponding SCB single difference sequence. Then using the Prophet model to predict SCB single difference sequence. Finally, the prediction result is substituted into the PPP positioning observation equation to obtain the positioning result. This paper uses the final ephemeris (IGF) published by IGS as a benchmark and compares the experimental results with IGU-P. For the selected four satellites, compared with the results of the IGU-P, the accuracy of SCB prediction of the model in this paper is improved by about 50.3%, 61.7%, 60.4%, and 48.8%. In terms of PPP positioning results, we use Real-time kinematic (RTK) measurements as a benchmark in this paper. Positioning accuracy has increased by 26%, 35%, and 19% in the N, E, and U directions, respectively. The results show that the Prophet model can improve the performance of PPP.
Merete Ellingjord-Dale , Nikos Papadimitriou, Michail Katsoulis, Chew Yee, Niki Dimou, Dipender Gill , Dagfinn Aune, Jue-Sheng Ong, Stuart MacGregor, Benjamin Elsworth, et al.
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0236904

Abstract:
Background Observational studies have reported either null or weak protective associations for coffee consumption and risk of breast cancer. Methods We conducted a two-sample Mendelian randomization (MR) analysis to evaluate the relationship between coffee consumption and breast cancer risk using 33 single-nucleotide polymorphisms (SNPs) associated with coffee consumption from a genome-wide association (GWA) study on 212,119 female UK Biobank participants of White British ancestry. Risk estimates for breast cancer were retrieved from publicly available GWA summary statistics from the Breast Cancer Association Consortium (BCAC) on 122,977 cases (of which 69,501 were estrogen receptor (ER)-positive, 21,468 ER-negative) and 105,974 controls of European ancestry. Random-effects inverse variance weighted (IVW) MR analyses were performed along with several sensitivity analyses to assess the impact of potential MR assumption violations. Results One cup per day increase in genetically predicted coffee consumption in women was not associated with risk of total (IVW random-effects; odds ratio (OR): 0.91, 95% confidence intervals (CI): 0.80–1.02, P: 0.12, P for instrument heterogeneity: 7.17e-13), ER-positive (OR = 0.90, 95% CI: 0.79–1.02, P: 0.09) and ER-negative breast cancer (OR: 0.88, 95% CI: 0.75–1.03, P: 0.12). Null associations were also found in the sensitivity analyses using MR-Egger (total breast cancer; OR: 1.00, 95% CI: 0.80–1.25), weighted median (OR: 0.97, 95% CI: 0.89–1.05) and weighted mode (OR: 1.00, CI: 0.93–1.07). Conclusions The results of this large MR study do not support an association of genetically predicted coffee consumption on breast cancer risk, but we cannot rule out existence of a weak association.
Satoshi Kurose , Katsuko Onishi, Nana Takao, Takumi Miyauchi, Kazuhisa Takahashi, Yutaka Kimura
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245678

Abstract:
Background Adiponectin has been reported to be associated with lower skeletal muscle mass and skeletal strength and may be involved in skeletal muscle regulation along with myostatin. This study aims to evaluate the association between serum adiponectin and myostatin levels and identify independent factors using body composition and metabolic parameters in patients with obesity. Methods Overall, 148 patients (age, 45.9 ± 14.3 years, body mass index, 37.2 ± 8.0 kg/m2) who initially visited the outpatient clinic of obesity between November 2013 and November 2019 were included. Body composition was measured using InBody 720 and dual energy X-ray absorptiometry. In addition, muscle strength, vascular function, and metabolic parameters were measured. Serum levels of adiponectin, leptin, myostatin, and irisin were measured from blood samples. Results The serum adiponectin level was 2.9 μg/mL (1.7–4.1 μg/mL), and the serum myostatin level was 2398.4 pg/mL (1,777.1–2952.5 pg/mL). The stepwise regression analysis revealed less leg strength, homeostasis model assessment of insulin resistance, and C-reactive protein as an independent predictor of serum adiponectin levels based on the significance of the univariate analysis (R2 = 0.190, P < 0.001). A high appendicular lean mass/body weight, reactive hyperemia index, and irisin were independent factors for serum myostatin levels (R2 = 0.260, P < 0.001) Conclusion The serum adiponectin level was associated with less muscle strength. Although serum myostatin was associated with a high appendicular lean mass, it is possible that myostatin was regulated by the percentage of body weight from appendicular lean mass.
Akihiko Kameyama , Risa Nishijima, Kimi Yamakoshi
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245607

Abstract:
Mucins, the major components of salivary mucus, are large glycoproteins abundantly modified with O-glycans. Mucins present on the surface of oral tissues contribute greatly to the maintenance of oral hygiene by selectively adhering to the surfaces of microbes via mucin O-glycans. However, due to the complex physicochemical properties of mucins, there have been relatively few detailed analyses of the mechanisms controlling the expression of mucin genes and the glycosyltransferase genes involved in glycosylation. Analysis performed using supported molecular matrix electrophoresis, a methodology developed for mucin analysis, and knockout mice without the polycomb group protein Bmi-1 revealed that Bmi-1 regulates mucin levels in the submandibular gland by suppressing the expression of the mucin Smgc gene, and that Bmi-1 also regulates mucin O-glycosylation via suppression of the glycosyltransferase Gcnt3 gene in the submandibular gland.
Hirotsugu Maruyama , Keiji Hanada, Akinori Shimizu, Tomoyuki Minami, Naomiti Hirano, Fumiaki Hino, Tomoyuki Abe, Hironobu Amano, Yasuhiro Fujiwara
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245447

Abstract:
Background Endoscopic ultrasonography (EUS) is proven to be a more specific and sensitive method for detecting pancreatic lesions. However, usefulness of EUS after pancreatectomy has not been reported. This study aimed to evaluate the observational capability of EUS for the remnant pancreas (RP) after pancreatectomy. Patient and methods This single-center, retrospective study enrolled 395 patients who underwent pancreatectomy at Onomichi General Hospital between December 2002 and March 2016, 45 patients who underwent EUS for RP were included for analysis. We evaluated the usefulness of EUS for RP using logistic regression analysis. Results Complete observation of the RP was done in 42 patients (93%). In the initial surgical procedure, 21 patients underwent pancreaticoduodenectomy (PD), and 24 patients underwent distal pancreatectomy (DP). PD and DP were observed in 85% (18/21) and 100% (24/24) cases, respectively. A comparison of the detection capability of EUS and contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) showed that EUS was significantly superior to contrast-enhanced CT or MRI (p < 0.01). Eight of the 45 patients showed recurrence lesions in the RP. The median recurrence period was 33 months. Predictive factors for recurrence in the univariate and multivariate analyses were significantly different in space occupying lesion with EUS findings (p < 0.01) and elevated CA19-9(p < 0.01). Conclusions EUS was able to observe the RP in almost all cases. In addition, the detection capability of EUS was significantly superior to those of CT or MRI. We recommend that all patients with RP should undergo EUS, and a longer follow-up must be performed.
Paul N. Zivich , Will Huang, Ali Walsh, Prabal Dutta, Marisa Eisenberg, Allison E. Aiello
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0243358

Abstract:
Office-based workplaces are an important but understudied context for infectious disease transmission. We examined the feasibility of two different sensors (Opos and Bluetooth beacons) for collecting person-to-person contacts and hand hygiene in office-based workplaces. Opo is an interaction sensor that captures sensor-to-sensor interactions through ultrasonic frequencies, which correspond to face-to-face contacts between study participants. Opos were additionally used to measure hand hygiene events by affixing sensors to soap and alcohol-based hand sanitizer dispensers. Bluetooth beacons were used in conjunction with a smartphone application and recorded proximity contacts between study participants. Participants in two office sites were followed for one-week in their workplace in March 2018. Contact patterns varied by time of day and day of the week. Face-to-face contacts were of shorter mean duration than proximity contacts. Supervisors had fewer proximity contacts but more face-to-face contacts than non-supervisors. Self-reported hand hygiene was substantively higher than sensor-collected hand hygiene events and duration of hand washing events was short (median: 9 seconds, range: 2.5–33 seconds). Given that office settings are key environments in which working age populations spend a large proportion of their time and interactions, a better characterization of empirical social networks and hand hygiene behaviors for workplace interactions are needed to mitigate outbreaks and prepare for pandemics. Our study demonstrates that implementing sensor technologies for tracking interactions and behaviors in offices is feasible and can provide new insights into real-world social networks and hygiene practices. We identified key social interactions, variability in hand hygiene, and differences in interactions by workplace roles. High-resolution network data will be essential for identifying the most effective ways to mitigate infectious disease transmission and develop pandemic preparedness plans for the workplace setting.
Dorothea Dumuid , Melissa Wake, David Burgner, Mark S. Tremblay, Anthony D. Okely, Ben Edwards, Terence Dwyer, Timothy Olds
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245501

Abstract:
Purpose Daily time spent on one activity cannot change without compensatory changes in others, which themselves may impact on health outcomes. Optimal daily activity combinations may differ across outcomes. We estimated optimal daily activity durations for the highest fitness and lowest adiposity. Methods Cross-sectional Child Health CheckPoint data (1182 11-12-year-olds; 51% boys) from the population-based Longitudinal Study of Australian Children were used. Daily activity composition (sleep, sedentary time, light physical activity [LPA], moderate-to-vigorous physical activity [MVPA]) was from 8-day, 24-hour accelerometry. We created composite outcomes for fitness (VO2max; standing long jump) and adiposity (waist-to-height ratio; body mass index; fat-to-fat-free log-ratio). Adjusted compositional models regressed activity log-ratios against each outcome. Best activity compositions (optimal time-use zones) were plotted in quaternary tetrahedrons; the overall optimal time-use composition was the center of the overlapping area. Results Time-use composition was associated with fitness and adiposity (all measures pfitness days had higher LPA (3.4 h) and shorter sleep (8.25 h), but optimal adiposity days had lower LPA (1.0 h) and longer sleep (10.9 h). Balancing both outcomes, the overall optimal time-use composition was (mean [range]): 10.2 [9.5; 10.5] h sleep, 9.9 [8.8; 11.2] h sedentary time, 2.4 [1.8; 3.2] h LPA and 1.5 [1.5; 1.5] h MVPA. Conclusion Optimal time use for children’s fitness and adiposity involves trade-offs. To best balance both outcomes, estimated activity durations for sleep and LPA align with, but for MVPA exceed, 24-h guidelines.
Anita Schmalor, Benjamin Y. Cheung, Steven J. Heine
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245517

Abstract:
Much research has shown that people tend to view genes in rather deterministic ways—often termed genetic essentialism. We explored how people would view the causes of ethnic stereotypes in contexts where human genetic variability was either emphasized or downplayed. In two studies with over 1600 participants we found that people viewed ethnic stereotypes to be more of a function of underlying genetics after they read an article describing how ancestry can be estimated by geographic distributions of gene frequencies than after reading an article describing how relatively homogeneous the human genome was or after reading a control essay. Moreover, people were more likely to attribute ethnic stereotypes to genes when they scored higher on a measure of genetic essentialism or when they had less knowledge about genes. Our understanding of stereotypes is a function of our understanding of genetics.
Daniel Bogale Odo , Alemayehu Gonie Mekonnen
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0243228

Abstract:
Background Handwashing is one of the most effective ways to prevent transmission of infectious diseases. A substantial body of research has examined the status and determinants of handwashing facilities in healthcare settings and schools. However, its status at home in the community, especially in developing countries, remains unclear. This study aimed to examine the availability and factors influencing basic handwashing facilities at households in Ethiopia. Method We analysed the 2016 Ethiopian Demographic and Health Survey (EDHS) data. EDHS employed a two-stage stratified cluster sampling technique. Data were collected from the lowest administrative unit (kebele). A multivariable logistic regression model that allowed cluster-level random effects was employed to examine factors that affect the availability of basic handwashing facilities (water plus soap) at households. Estimates from the regression model are reported as odds ratios (ORs) with standard errors clustered at the DHS cluster level to account for a sampling methodology. Results In our sample, only 1292 (8% [95% CI, 7.6%–8.4%]) of the households had basic handwashing facilities. Compared with head of household who had no formal education, the odds of having basic handwashing facilities was higher among head of household who completed secondary level of education (adjusted odds ratio [AOR] = 1.83; 95% CI: 1.35–2.49) and higher level of education (AOR = 2.35; 95% CI: 1.63–3.39). Odds of having basic handwashing facilities was increased with having radio (AOR = 1.32; 95% CI: 1.10–1.63) and television (AOR = 1.49; 95% CI: 1.10–2.02) at home. Households that had improved latrine were two times more likely to have basic handwashing facilities (AOR = 2.09; 95% CI: 1.56–2.80). Being at higher household wealth quintiles was associated with increased odds of having basic handwashing facilities. Conclusion Very low basic handwashing facilities was demonstrated by this study, whereas, awareness and socio-economic related factors were identified as a determinants for its availability in the household. Greater efforts are needed to increase the coverage of community-level handwashing facilities.
Hillary Mugiyo , Vimbayi G. P. Chimonyo, Mbulisi Sibanda, Richard Kunz, Luxon Nhamo, Cecelia R. Masemola, Caroline Dalin, Albert T. Modi, Tafadzwa Mabhaudhi
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0244734

Abstract:
Several neglected and underutilised species (NUS) provide solutions to climate change and creating a Zero Hunger world, the Sustainable Development Goal 2. Several NUS are drought and heat stress-tolerant, making them ideal for improving marginalised cropping systems in drought-prone areas. However, owing to their status as NUS, current crop suitability maps do not include them as part of the crop choices. This study aimed to develop land suitability maps for selected NUS [sorghum, (Sorghum bicolor), cowpea (Vigna unguiculata), amaranth and taro (Colocasia esculenta)] using Analytic Hierarchy Process (AHP) in ArcGIS. Multidisciplinary factors from climatic, soil and landscape, socio-economic and technical indicators overlaid using Weighted Overlay Analysis. Validation was done through field visits, and area under the curve (AUC) was used to measure AHP model performance. The results indicated that sorghum was highly suitable (S1) = 2%, moderately suitable (S2) = 61%, marginally suitable (S3) = 33%, and unsuitable (N1) = 4%, cowpea S1 = 3%, S2 = 56%, S3 = 39%, N1 = 2%, amaranth S1 = 8%, S2 = 81%, S3 = 11%, and taro S1 = 0.4%, S2 = 28%, S3 = 64%, N1 = 7%, of calculated arable land of SA (12 655 859 ha). Overall, the validation showed that the mapping exercises exhibited a high degree of accuracies (i.e. sorghum AUC = 0.87, cowpea AUC = 0.88, amaranth AUC = 0.95 and taro AUC = 0.82). Rainfall was the most critical variable and criteria with the highest impact on land suitability of the NUS. Results of this study suggest that South Africa has a huge potential for NUS production. The maps developed can contribute to evidence-based and site-specific recommendations for NUS and their mainstreaming. Also, the maps can be used to design appropriate production guidelines and to support existing policy frameworks which advocate for sustainable intensification of marginalised cropping systems through increased crop diversity and the use of stress-tolerant food crops.
Feng Zhang, Shihang Wang , Mingsong Zhao, Falv Qin, Xiaoyu Liu
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245040

Abstract:
Soil organic carbon content has a significant impact on soil fertility and grain yield, making it an important factor affecting agricultural production and food security. Dry farmland, the main type of cropland in China, has a lower soil organic carbon content than that of paddy soil, and it may have a significant carbon sequestration potential. Therefore, in this study we applied the CENTURY model to explore the temporal and spatial changes of soil organic carbon (SOC) in Jilin Province from 1985 to 2015. Dry farmland soil polygons were extracted from soil and land use layers (at the 1:1,000,000 scale). Spatial overlay analysis was also used to extract 1282 soil polygons from dry farmland. Modelled results for SOC dynamics in the dry farmland, in conjunction with those from the Yushu field-validation site, indicated a good level of performance. From 1985 to 2015, soil organic carbon density (SOCD) of dry farmland decreased from 34.36 Mg C ha−1 to 33.50 Mg C ha−1 in general, having a rate of deterioration of 0.03 Mg C ha−1 per year. Also, SOC loss was 4.89 Tg from dry farmland soils in the province, with a deterioration rate of 0.16 Tg C per year. 35.96% of the dry farmland its SOCD increased but 64.04% of the area released carbon. Moreover, SOC dynamics recorded significant differences between different soil groups. The method of coupling the CENTURY model with a detailed soil database can simulate temporal and spatial variations of SOC at a regional scale, and it can be used as a precise simulation method for dry farmland SOC dynamics.
Huadi Shi, Yuling Song , Zhi Song, Chun Huang
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245524

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Background Lower-grade glioma (LGG) is the most common histology identified in glioma. CKMT1B has not been investigated in glioma. The purpose of this research was to investigate the prognostic value of CKMT1B and its correlation with immune infiltration in LGG. Methods We used Gene Expression Profiling Interactive Analysis (GEPIA) to analyze the expression of CKMT1B in LGG. Univariate and multivariate Cox regression analyses were used to assess the effect of CKMT1B expression and screened variables on survival. The correlation between CKMT1B and immune infiltration was evaluated by TIMER and CIBERSORT. Moreover, the possible biological functions of CKMT1B were studied by GSEA. The statistical analysis was conducted by R software. Results The expression of CKMT1B was significantly lower than the normal samples in LGG. Low expression of CKMT1B predicts a worse prognosis. Multivariate Cox analyses revealed that CKMT1B might be an independent favorable prognostic indicator. TIMER analysis revealed that CKMT1B expression level was related to immune infiltration. CIBERSORT analysis showed that CKMT1B expression was positively related to the infiltration level of activated mast cells and negatively related to macrophage M2 in LGG. Moreover, GESA showed that multiple cancer-related and immune-related gene sets were enriched in the low-CKMT1B group in the top 5 of the most significant differences. Conclusion CKMT1B is a prognostic biomarker with potential applications and associated with immune infiltration in Lower-grade glioma.
Swee Hung Ang, Wen Yea Hwong, Michiel L. Bots, Sheamini Sivasampu, Aznida Firzah Abdul Aziz, Fan Kee Hoo , Ilonca Vaartjes
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245448

Abstract:
Background and objectives Risk of readmissions is an important quality indicator for stroke care. Such information is limited among low- and middle-income countries. We assessed the trends for 28-day readmissions after a stroke in Malaysia from 2008 to 2015 and evaluated the causes and factors associated with readmissions in 2015. Methods Using the national hospital admission records database, we included all stroke patients who were discharged alive between 2008 and 2015 for this secondary data analysis. The risk of readmissions was described in proportion and trends. Reasons were coded according to the International Classification of Diseases, 10th Edition. Multivariable logistic regression was performed to identify factors associated with readmissions. Results Among 151729 patients, 11 to 13% were readmitted within 28 days post-discharge from their stroke events each year. The trend was constant for ischemic stroke but decreasing for hemorrhagic stroke. The leading causes for readmissions were recurrent stroke (32.1%), pneumonia (13.0%) and sepsis (4.8%). The risk of 28-day readmission was higher among those with stroke of hemorrhagic (adjusted odds ratio (AOR): 1.52) and subarachnoid hemorrhage (AOR: 2.56) subtypes, and length of index admission >3 days (AOR: 1.48), but lower among younger age groups of 35–64 (AORs: 0.61–0.75), p values Conclusion The risk of 28-day readmission remained constant from 2008 to 2015, where one in eight stroke patients required readmission, mainly attributable to preventable causes. Age, ethnicity, stroke subtypes and duration of the index admission influenced the risk of readmission. Efforts should focus on minimizing potentially preventable admissions, especially among those at higher risk.
Stephane Becart, Karen B. Whittington, Amanda Prislovsky, Navin L. Rao, Edward F. Rosloniec
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245541

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While antibodies to citrullinated proteins have become a diagnostic hallmark in rheumatoid arthritis (RA), we still do not understand how the autoimmune T cell response is influenced by these citrullinated proteins. To investigate the role of citrullinated antigens in HLA-DR1- and DR4-restricted T cell responses, we utilized mouse models that express these MHC-II alleles to determine the relationship between citrullinated peptide affinity for these DR molecules and the ability of these peptides to induce a T cell response. Using a set of peptides from proteins thought to be targeted by the autoimmune T cell responses in RA, aggrecan, vimentin, fibrinogen, and type II collagen, we found that while citrullination can enhance the binding affinity for these DR alleles, it does not always do so, even when in the critical P4 position. Moreover, if peptide citrullination does enhance HLA-DR binding affinity, it does not necessarily predict the generation of a T cell response. Conversely, citrullinated peptides can stimulate T cells without changing the peptide binding affinity for HLA-DR1 or DR4. Furthermore, citrullination of an autoantigen, type II collagen, which enhances binding affinity to HLA-DR1 did not enhance the severity of autoimmune arthritis in HLA-DR1 transgenic mice. Additional analysis of clonal T cell populations stimulated by these peptides indicated cross recognition of citrullinated and wild type peptides can occur in some instances, while in others cases the citrullination generates a novel T cell epitope. Finally, cytokine profiles of the wild type and citrullinated peptide stimulated T cells unveiled a significant disconnect between proliferation and cytokine production. Altogether, these data demonstrate the lack of support for a simplified model with universal correlation between affinity for HLA-DR alleles, immunogenicity and arthritogenicity of citrullinated peptides. Additionally they highlight the complexity of both T cell receptor recognition of citrulline as well as its potential conformational effects on the peptide:HLA-DR complex as recognized by a self-reactive cell receptor.
Patrick Nekula, Clemens Koob
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245276

Abstract:
Introduction The aging of staff and skill shortage are major challenges for social enterprises. Nurturing a workplace culture of health and fostering employee engagement could be starting points to combat these challenges. The associations between these two factors have received comparatively little attention from the scientific community, in particular with regard to social enterprises. Hence, this study aims to examine those associations, drawing on the job demands-resources theory and the social-ecological workplace culture of health model. It is hypothesized that employees’ self-rated health acts as a mediator in the relationship between culture of health and employee engagement and that health as personal value works as a moderator. Method The study used the Workplace Culture of Health scale to measure culture of health in social enterprises and UWES-9 to assess employee engagement. Data was collected administering a quantitative online survey among employees of social enterprises in Germany. The dataset for analyses comprised N = 172 employees in total. Data analyses included Pearson’s correlations, regression analysis, as well as mediation, moderation and moderated mediation analyses. Results Culture of health is a predictor of employee engagement in social enterprises. The analyses demonstrate a moderate association between culture of health and employee engagement. Indications were found that employees’ self-rated health acts as a mediator and that health as personal value acts as a moderator between culture of health and employee engagement in social enterprises. Discussion This study suggests that fostering a culture of health in social enterprises does not only have a positive effect on employee health, but also on employee engagement. This applies in particular when employees attribute great value to their health, which is to be expected even more in future. Hence, nurturing a culture of health becomes a pivotal management task in social enterprises. Moreover, a comprehensive assessment of the benefits of health promotion programs in social enterprises should not only consider their health-related outcomes, but also factor in their impact on employee engagement.
Laurie E. Davies , Andrew Kingston, Adam Todd, Barbara Hanratty
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245648

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Background Polypharmacy is potentially harmful and under-researched amongst the fastest growing subpopulation, the very old (aged ≥85). We aimed to characterise polypharmacy using data from the Newcastle 85+ Study—a prospective cohort of people born in 1921 who turned 85 in 2006 (n = 845). Methods The prevalence of polypharmacy at baseline (mean age 85.5) was examined using cut-points of 0, 1, 2–4, 5–9 and ≥10 medicines—so-called ‘no polypharmacy’, ‘monotherapy’, ‘minor polypharmacy’, ‘polypharmacy’ and ‘hyperpolypharmacy.’ Cross-tabulations and upset plots identified the most frequently prescribed medicines and medication combinations within these categories. Mixed-effects models assessed whether gender and socioeconomic position were associated with prescribing changes over time (mean age 85.5–90.5). Participant characteristics were examined through descriptive statistics. Results Complex multimorbidity (44.4%, 344/775) was widespread but hyperpolypharmacy was not (16.0%, 135/845). The median medication count was six (interquartile range 4–8). Preventative medicines were common to all polypharmacy categories, and prescribing regimens were diverse. Nitrates and oral anticoagulants were more frequently prescribed for men, whereas bisphosphonates, non-opioid analgesics and antidepressants were more common in women. Cardiovascular medicines, including loop diuretics, tended to be more frequently prescribed for socioeconomically disadvantaged people (th centile Index of Multiple Deprivation (IMD)), despite no difference in the prevalence of cardiovascular disease (p = 0.56) and diabetes (p = 0.92) by IMD. Conclusion Considering their complex medical conditions, prescribing is relatively conservative amongst 85-year-olds living in North East England. Prescribing shows significant gender and selected socioeconomic differences. More support for managing preventative medicines, of uncertain benefit, might be helpful in this population.
Ming Huo , Na Zhao, Yue Zhao, Wim Van Den Noortgate
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245549

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A teaching workforce with good quality is a key factor in the process of China’s rapid development. Although 76% of Chinese pupils are studying at schools within county areas, a general portray of the corresponding teaching workforce is still not clear. This study presents data from a nationally representative survey of primary education teachers in 35 counties of 18 provinces in China. Findings presented include demographic and professional characteristics, living conditions as well as attitudes towards work. Besides, variations among school locations and geographical regions are also examined. The key findings are the followings: 1) Quality of primary school teachers in county areas has been improved regarding education background; 2) Teaching force in village primary schools has an unbalanced age and gender composition; 3) Out-of-field teaching practice is widespread, especially for minor subjects. 4) Primary school teachers perceived relative low salary and low social status.
Matthew Calamia , Daniel S. Weitzner, Alyssa N. De Vito, John P. K. Bernstein, Ray Allen, Jeffrey N. Keller
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0244962

Abstract:
The coronavirus disease pandemic has brought a new urgency for the development and deployment of web-based applications which complement, and offer alternatives to, traditional one-on-one consultations and pencil-and-paper (PaP) based assessments that currently dominate clinical research. We have recently developed a web-based application that can be used for the self-administered collection of patient demographics, self-rated health, depression and anxiety, and cognition as part of a single platform. In this study we report the findings from a study with 155 cognitively healthy older adults who received established PaP versions, as well as our novel computerized measures of self-rated health, depression and anxiety, and cognition. Moderate to high correlations were observed between PaP and web- based measures of self-rated health (r = 0.77), depression and anxiety (r = 0.72), and preclinical Alzheimer’s disease cognitive composite (PACC) (r = .61). Test-retest correlations were variable with high correlations for a measure of processing speed and a measure of delayed episodic memory. Taken together, these data support the feasibility and validity of utilization of this novel web-based platform as a new alternative for collecting patient demographics and the assessment of self-rated health, depression and anxiety, and cognition in the elderly.
Takeshi Hiu, Shimpei Morimoto, Ayaka Matsuo, Kei Satoh, Hiroaki Otsuka, Fumiya Kutsuna, Keisuke Ozono, Kosuke Hirayama, Chikaaki Nakamichi, Kazumi Yamasaki, et al.
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245082

Abstract:
Background Mechanical thrombectomy (MT) is standard treatment for acute ischemic stroke (AIS) with large-vessel occlusion within 6 h of symptom onset to treatment initiation (OTP). Recent trials have extended the therapeutic time window for MT to within 24 h. However, MT treatment remains low in remote areas. Nagasaki Prefecture, Japan has many inhabited islands with no neurointerventionalists. Our hospital on the mainland is a regional hub for eight island hospitals. We evaluated clinical outcomes of MT for patients with AIS on these islands versus on the mainland. Methods During 2014–2019, we reviewed consecutive patients with AIS who received MT at our hospital. Patients comprised the Islands group and Mainland group. Patient characteristics and clinical outcomes were compared between groups. Results We included 91 patients (Islands group: 15 patients, Mainland group: 76 patients). Seven patients (46.7%) in the Islands group versus 43 (56.6%) in the Mainland group achieved favorable outcomes. Successful recanalization was obtained in 11 patients (73.3%) on the islands and 67 (88.2%) on the mainland. The median OTP time in the Islands was 365 min. In both the Islands and Mainland groups, the OTP time and successful recanalization were associated with functional outcome. The modified Rankin Scale (mRS) score at 90 days ≤2 was obtained in two patients and mRS = 3 in four patients among eight patients with OTP time >6 h. Conclusions Few patients with AIS on remote islands have received MT. Although patients who underwent MT on the islands had longer OTP, the clinical outcomes were acceptable. OTP time on remote islands must be shortened, as this is related to functional outcome. In some cases with successful recanalization, a favorable outcome can still be obtained even after 6 h. Even if OTP exceeds 6 h, it is desirable to appropriately select patients and actively perform MT.
Correction
Ali Hassan Shabbir, Jiquan Zhang, James D. Johnston, Samuel Asumadu Sarkodie, James A. Lutz, Xingpeng Liu
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245828

Younes El Fersioui , Gaëtan Pinton, Nathalie Allaman-Pillet, Daniel F. Schorderet
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245239

Abstract:
H6 family homeobox 1 (HMX1) regulates multiple aspects of craniofacial development as it is widely expressed in the eye, peripheral ganglia and branchial arches. Mutations in HMX1 are linked to an ocular defect termed Oculo-auricular syndrome of Schorderet-Munier-Franceschetti (MIM #612109). We identified UHRF1 as a target of HMX1 during development. UHRF1 and its partner proteins actively regulate chromatin modifications and cellular proliferation. Luciferase assays and in situ hybridization analyses showed that HMX1 exerts a transcriptional inhibitory effect on UHRF1 and a modification of its expression pattern. Overexpression of hmx1 in hsp70-hmx1 zebrafish increased uhrf1 expression in the cranial region, while mutations in the hmx1 dimerization domains reduced uhrf1 expression. Moreover, the expression level of uhrf1 and its partner dnmt1 was increased in the eye field in response to hmx1 overexpression. These results indicate that hmx1 regulates uhrf1 expression and, potentially through regulating the expression of factors involved in DNA methylation, contribute to the development of the craniofacial region of zebrafish.
Confidence Alorse Atakro , Abigail Atakro, Janet Sintim Aboagye, Alice Aluwah Blay, Stella Boatemaa Addo, Dorcas Frempomaa Agyare, Peter Adatara, Kwaku Gyimah Amoa-Gyarteng, Awube Menlah, Isabella Garti, et al.
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245451

Abstract:
Background The increase in the number of elderly persons in developing countries has not had a corresponding increase in social and health care support systems for the elderly. There is a substantial difference in the quality of healthcare received by older people in developing and developed countries. Elderly persons in developing countries including Ghana are increasingly becoming marginalised and isolated. There is, however, limited evidence of healthcare challenges and expectations by elderly persons in Ghana. This study explored healthcare challenges and expectations of elderly persons to inform policy that could lead to improved quality of life for elderly persons in Ghana. Materials and methods Qualitative exploratory descriptive study design was used in conducting this study. Semi-structured interviews were used in collecting data from 30 participants from three regions in Ghana (10 from each region). Data analysis was carried out through content analysis. Results Four themes were extracted from data. These themes were: 1. Inadequate information from health workers regarding care of the older person. 2. Queuing frustrations. 3. Financial burden. 4. Focused elderly care demand. Conclusion The elderly in Ghana experience challenges of healthcare which include inadequate information, queuing frustrations and financial burdens. Elderly persons also have expectations of healthcare which include having dedicated professionals and units that will attend to them during their hospital visits. Academic and clinical gerontology experts could collaborate and help improve gerontology knowledge of health workers through workshops and conferences. Improving knowledge of health workers in gerontology may be a positive step towards meeting healthcare expectations of older Ghanaians.
Alireza Ermagun , Nazanin Tajik
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245396

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In a progressively interconnected world, the loss of system resilience has consequences for human health, the economy, and the environment. Research has exploited the science of networks to explain the resilience of complex systems against random attacks, malicious attacks, and the localized attacks induced by natural disasters or mass attacks. Little is known about the elucidation of system recovery by the network topology. This study adds to the knowledge of network resilience by examining the nexus of recoverability and network topology. We establish a new paradigm for identifying the recovery behavior of networks and introduce the recoverability measure. Results indicate that the recovery response behavior and the recoverability measure are the function of both size and topology of networks. In small sized networks, the return to recovery exhibits homogeneous recovery behavior over topology, while the return shape is dispersed with an increase in the size of network. A network becomes more recoverable as connectivity measures of the network increase, and less recoverable as accessibility measures of network increase. Overall, the results not only offer guidance on designing recoverable networks, but also depict the recovery nature of networks deliberately following a disruption. Our recovery behavior and recoverability measure has been tested on 16 distinct network topologies. The relevant recovery behavior can be generalized based on our definition for any network topology recovering deliberately.
Michaël Bertrand-Charette, Jens Bo Nielsen, Laurent J. Bouyer
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245523

Abstract:
Objective Task-specific training is often used in functional rehabilitation for its potential to improve performance at locomotor tasks in neurological populations. As push-off impairment are often seen with these patients, this functional approach shows potential to retrain gait overground to normalize the gait pattern and retrain the ability to improve gait speed. The main objective of this project was to validate, in healthy participants, a simple, low-cost push-off retraining protocol based on task-specific training that could be implemented during overground walking in the clinic. Methods 30 healthy participants walked in an 80-meter long corridor before, during, and after the application of an elastic resistance to the right ankle. Elastic tubing attached to the front of a modified ankle-foot orthosis delivered the resistance during push-off. Relative ankle joint angular displacements were recorded bilaterally and continuously during each walking condition. Results On the resisted side, participants presented aftereffects (increased peak plantarflexion angle from 13.4±4.2° to 20.0±6.4°, p Conclusion This study shows the feasibility of modifying push-off kinematics using an elastic resistance applied at the ankle while walking overground. This approach represents an interesting venue for future gait rehabilitation.
Inês Vieira Da Silva , Bárbara P. Soares, Catarina Pimpão , Rui M. A. Pinto , Teresa Costa, João P. B. Freire, Etienne Corrent, Tristan Chalvon-Demersay, José A. M. Prates, Paula A. Lopes , et al.
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245739

Abstract:
The regulation of glycerol permeability in the gastrointestinal tract is crucial to control fat deposition, lipolysis and gluconeogenesis. Knowing that the amino acid glutamine is a physiological regulator of gluconeogenesis, whereas cystine promotes adiposity, herein we investigated the effects of dietary supplementation with glutamine and cystine on the serum biochemical parameters of piglets fed on amino acid-enriched diets, as well as on the transcriptional profile of membrane water and glycerol channels aquaporins (AQPs) in the ileum portion of the small intestine and its impact on intestinal permeability. Twenty male piglets with an initial body weight of 8.8 ± 0.89 kg were allocated to four dietary treatments (n = 5) and received, during a four week-period, a basal diet without supplementation (control) or supplemented with 8 kg/ton of glutamine (Gln), cystine (Cys) or the combination of the two amino acids in equal proportions (Gln + Cys). Most biochemical parameters were found improved in piglets fed Gln and Cys diet. mRNA levels of AQP3 were found predominant over the others. Both amino acids, individually or combined, were responsible for a consistent downregulation of AQP1, AQP7 and AQP10, without impacting on water permeability. Conversely, Cys enriched diet upregulated AQP3 enhancing basolateral membranes glycerol permeability and downregulating glycerol kinase (GK) of intestinal cells. Altogether, our data reveal that amino acids dietary supplementation can modulate intestinal AQPs expression and unveil AQP3 as a promising target for adipogenesis regulation.
Xinying Wang, Shohei Asami, Daisuke Kitamura
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245608

Abstract:
Accumulating evidence has suggested a correlation of tumor infiltrating B cells (TiBcs) and a good prognosis of cancer diseases. In some cases, TiBcs appear to have experienced antigen stimulation since they have undergone class-switching and somatic hypermutation and formed tertiary lymphoid structures around tumors together with T cells. Assuming TiBcs include those that recognize some tumor antigens, we sought to investigate their possible usefulness for cell-mediated immunotherapies. To expand usually small number of TiBcs in vitro, we modified our B cell culture system: we transduced B cells with ERT2-Bach2 so that they grow unlimitedly provided with tamoxifen, IL-21 and our original feeder cells. Such cells differentiate into plasma cells and produce antibodies upon withdrawal of tamoxifen, and further by addition of a Bach2-inhibitor in vitro. As a preliminary experiment, thus expanded splenic B cells expressing a transgenic antigen receptor/antibody against hen egg lysozyme were intravenously injected into mice pre-implanted with B16 melanoma cells expressing membrane-bound HEL in the skin, which resulted in suppression of the growth of B16 tumors and prolonged survival of the recipient mice. To test the usefulness of TiBcs for the immunotherapy, we next used APCmin/+ mice as a model that spontaneously develop intestinal tumors. We cultured TiBcs separated from the tumors of APCmin/+ mice as above and confirmed that the antibodies they produce recognize the APCmin/+ tumor. Repeated injection of such TiBcs into adult APCmin/+ mice resulted in suppression of intestinal tumor growth and elongation of the survival of the recipient mice. Serum antibody from the TiBc-recipient mice selectively bound to an antigen expressed in the tumor of APCmin/+ mice. These data suggest a possibility of the novel individualized cancer immunotherapy, in which TiBcs from surgically excised tumor tissues are expanded and infused into the donor patients.
Caroline Rönnberg, Allan Lugaajju, Anna Nyman, Ulf Hammar, Matteo Bottai, Maximilian Julius Lautenbach, Christopher Sundling, Fred Kironde, Kristina E. M. Persson
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245431

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Malaria is a potentially life-threatening disease with approximately half of the world’s population at risk. Young children and pregnant women are hit hardest by the disease. B cells and antibodies are part of an adaptive immune response protecting individuals continuously exposed to the parasite. An infection with Plasmodium falciparum can cause dysregulation of B cell homeostasis, while antibodies are known to be key in controlling symptoms and parasitemia. BAFF is an instrumental cytokine for the development and maintenance of B cells. Pregnancy alters the immune status and renders previously clinically immune women at risk of severe malaria, potentially due to altered B cell responses associated with changes in BAFF levels. In this prospective study, we investigated the levels of BAFF in a malaria-endemic area in mothers and their infants from birth up to 9 months. We found that BAFF-levels are significantly higher in infants than in mothers. BAFF is highest in cord blood and then drops rapidly, but remains significantly higher in infants compared to mothers even at 9 months of age. We further correlated BAFF levels to P. falciparum-specific antibody levels and B cell frequencies and found a negative correlation between BAFF and both P. falciparum-specific and total proportions of IgG+ memory B cells, as well as CD27− memory B cells, indicating that exposure to both malaria and other diseases affect the development of B-cell memory and that BAFF plays a part in this. In conclusion, we have provided new information on how natural immunity against malaria is formed.
Suzanne A. E. Nooij , Christopher J. Bockisch, Heinrich H. Bülthoff, Dominik Straumann
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245295

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Illusory self-motion often provokes motion sickness, which is commonly explained in terms of an inter-sensory conflict that is not in accordance with previous experience. Here we address the influence of cognition in motion sickness and show that such a conflict is not provocative when the observer believes that the motion illusion is indeed actually occurring. Illusory self-motion and motion sickness were elicited in healthy human participants who were seated on a stationary rotary chair inside a rotating optokinetic drum. Participants knew that both chair and drum could rotate but were unaware of the actual motion stimulus. Results showed that motion sickness was correlated with the discrepancy between participants’ perceived self-motion and participants’ beliefs about the actual motion. Together with the general motion sickness susceptibility, this discrepancy accounted for 51% of the variance in motion sickness intensity. This finding sheds a new light on the causes of visually induced motion sickness and suggests that it is not governed by an inter-sensory conflict per se, but by beliefs concerning the actual self-motion. This cognitive influence provides a promising tool for the development of new countermeasures.
Flavia Venditti , Aviad Agam, Jacopo Tirillò, Stella Nunziante-Cesaro, Ran Barkai
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245595

Abstract:
Chopping tools/choppers provide one of the earliest and most persistent examples of stone tools produced and used by early humans. These artifacts appeared for the first time ~2.5 million years ago in Africa and are characteristic of the Oldowan and Acheulean cultural complexes throughout the Old World. Chopping tools were manufactured and used by early humans for more than two million years regardless of differences in geography, climate, resource availability, or major transformations in human cultural and biological evolution. Despite their widespread distribution through time and space in Africa and Eurasia, little attention has been paid to the function of these items, while scholars still debate whether they are tools or cores. In this paper, we wish to draw attention to these prominent and ubiquitous early lithic artifacts through the investigation of 53 chopping tools retrieved from a specific context at Late Acheulean Revadim (Israel). We combined typo-technological and functional studies with a residue analysis aimed at shedding light on their functional role within the tool-kits of the inhabitants of the site. Here we show that most of the chopping tools were used to chop hard and medium materials, such as bone, most probably for marrow extraction. A few of the tools were also used for cutting and scraping activities, while some also served as cores for further flake detachment. The chopping tools exhibit extraordinarily well-preserved bone residues suggesting they were used mainly for bone-breaking and marrow acquisition. We discuss the data and explore the tool versus core debate also in light of a sample of 50 flake cores made on pebbles/cobbles retrieved from the same archeological layer. The results add further pieces to the puzzle of activities carried out at Revadim and add to our knowledge of the production and use of these enigmatic tools and their role in human evolutionary history.
Andrew L. Gregory, Paul K. Piff
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245651

Abstract:
How do interactions with an ideologically extreme online community affect cognition? In this paper, we examine whether engagement with an online neo-Nazi forum is associated with more one-sided, “black and white” thinking. Using naturalistic language data, we examined differences in integrative complexity, a measure of the degree to which people acknowledge and reconcile conflicting ideas and viewpoints, and contrasted it with Language Style Matching, a measure of group cohesion. In a large web scraping study (N = 1,891), we tested whether two measures of engagement and interaction with the community are associated with less complex, balanced cognition. Using hierarchical regression modeling, we found that both individuals who had been community members for longer and those who had posted more tended to show less complexity in their language, even when accounting for mean differences between individuals. However, these differences in integrative complexity were distinct from group cohesion, which actually decreased with our measures of engagement. Despite small effect sizes, these findings indicate that ideologically extreme online communities may exacerbate the views of their members and contribute to ever-widening polarized cognitions.
Valentina Presta , Francesca Paraboschi, Filippo Marsella, Valeria Lucarini, Daniela Galli, Prisco Mirandola, Antonio Banchini, Carlo Marchesi, Laura Galuppo, Marco Vitale , et al.
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245661

Abstract:
While correlations between postural stability deficits and schizophrenia are well documented, information on dynamic motor alterations in schizophrenia are still scarce, and no data on their onset are available yet. Therefore, the aim of this study was i) to measure gait pattern(s) in patients with schizophrenia; ii) to identify posture and gait alterations which could potentially be used as a predictive clinical tool of the onset of the disorder. Body composition, posture and gait parameters were assessed in a group of 30 patients with schizophrenia and compared to 25 healthy subjects. Sway area was significantly higher in the schizophrenia group compared to controls regardless of whether the participants were in eyes open or eyes closed condition. Gait cadence and speed were significantly lower in patients with schizophrenia, while stride length was similar. We concluded that the combination of an increased sway area (independent from eye closure) and a gait cadence reduction—in the presence of normal gait speed and stride length—might be considered peculiar postural and gait profile characteristic of early schizophrenia.
William P. T. M. Van Doorn, Patricia M. Stassen, Hella F. Borggreve, Maaike J. Schalkwijk, Judith Stoffers, Otto Bekers, Steven J. R. Meex
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245157

Abstract:
Introduction Patients with sepsis who present to an emergency department (ED) have highly variable underlying disease severity, and can be categorized from low to high risk. Development of a risk stratification tool for these patients is important for appropriate triage and early treatment. The aim of this study was to develop machine learning models predicting 31-day mortality in patients presenting to the ED with sepsis and to compare these to internal medicine physicians and clinical risk scores. Methods A single-center, retrospective cohort study was conducted amongst 1,344 emergency department patients fulfilling sepsis criteria. Laboratory and clinical data that was available in the first two hours of presentation from these patients were randomly partitioned into a development (n = 1,244) and validation dataset (n = 100). Machine learning models were trained and evaluated on the development dataset and compared to internal medicine physicians and risk scores in the independent validation dataset. The primary outcome was 31-day mortality. Results A number of 1,344 patients were included of whom 174 (13.0%) died. Machine learning models trained with laboratory or a combination of laboratory + clinical data achieved an area-under-the ROC curve of 0.82 (95% CI: 0.80–0.84) and 0.84 (95% CI: 0.81–0.87) for predicting 31-day mortality, respectively. In the validation set, models outperformed internal medicine physicians and clinical risk scores in sensitivity (92% vs. 72% vs. 78%;p0.02). The model had higher diagnostic accuracy with an area-under-the-ROC curve of 0.85 (95%CI: 0.78–0.92) compared to abbMEDS (0.63,0.54–0.73), mREMS (0.63,0.54–0.72) and internal medicine physicians (0.74,0.65–0.82). Conclusion Machine learning models outperformed internal medicine physicians and clinical risk scores in predicting 31-day mortality. These models are a promising tool to aid in risk stratification of patients presenting to the ED with sepsis.
Makobu Kimani, Elise M. Van Der Elst, Oscar Chirro, Elizabeth Wahome, Fauz Ibrahim, Nana Mukuria, Tobias F. Rinke De Wit, Susan M. Graham, Don Operario, Eduard J. Sanders
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0244226

Abstract:
Background Transgender women (TGW) and men who have sex with men (MSM) in sub-Saharan Africa have high HIV acquisition risks and can benefit from daily pre-exposure prophylaxis (PrEP). We assessed PrEP adherence by measuring tenofovir-diphosphate (TFV-DP) levels and explore motives for PrEP persistence in TGW and MSM. Methods Participants were enrolled in a one-year PrEP programme and made quarterly visits irrespective of whether they were still using PrEP. At their month 6 visit, participants provided a dried blood spot to test for TFV-DP levels; protective levels were defined as those compatible with ≥4 pills per week (700–1249 fmol/punch). Before TFV-DP levels were available, a sub-set of these participants were invited for an in-depth interview (IDI). Semi-structured IDI topic guides were used to explore motives to uptake, adhere to, and discontinue PrEP. IDI data were analyzed thematically. Results Fifty-three participants (42 MSM and 11 TGW) were enrolled. At month 6, 11 (20.7%) participants (8 MSM and 3 TGW) were lost to follow up or stopped taking PrEP. Any TFV-DP was detected in 62.5% (5/8) of TGW vs. 14.7% of MSM (5/34, p = 0.01). Protective levels were detected in 37.5% of TGW (3/8), but not in any MSM. Nineteen IDI were conducted with 7 TGW and 9 MSM on PrEP, and 1 TGW and 2 MSM off PrEP. Unplanned or frequent risky sexual risk behaviour were the main motives for PrEP uptake. Among participants on PrEP, TGW had a more complete understanding of the benefits of PrEP. Inconsistent PrEP use was attributed to situational factors. Motives to discontinue PrEP included negative reactions from partners and stigmatizing healthcare services. Conclusion While MSM evinced greater adherence challenges in this PrEP programme, almost 40% of TGW were protected by PrEP. Given high HIV incidences in TGW these findings hold promise for TGW PrEP programming in the region.
Li-Pang Chen , Qihuang Zhang, Grace Y. Yi , Wenqing He
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0244536

Abstract:
Background Since March 11, 2020 when the World Health Organization (WHO) declared the COVID-19 pandemic, the number of infected cases, the number of deaths, and the number of affected countries have climbed rapidly. To understand the impact of COVID-19 on public health, many studies have been conducted for various countries. To complement the available work, in this article we examine Canadian COVID-19 data for the period of March 18, 2020 to August 16, 2020 with the aim to forecast the dynamic trend in a short term. Method We focus our attention on Canadian data and analyze the four provinces, Ontario, Alberta, British Columbia, and Quebec, which have the most severe situations in Canada. To build predictive models and conduct prediction, we employ three models, smooth transition autoregressive (STAR) models, neural network (NN) models, and susceptible-infected-removed (SIR) models, to fit time series data of confirmed cases in the four provinces separately. In comparison, we also analyze the data of daily infections in two states of USA, Texas and New York state, for the period of March 18, 2020 to August 16, 2020. We emphasize that different models make different assumptions which are basically difficult to validate. Yet invoking different models allows us to examine the data from different angles, thus, helping reveal the underlying trajectory of the development of COVID-19 in Canada. Finding The examinations of the data dated from March 18, 2020 to August 11, 2020 show that the STAR, NN, and SIR models may output different results, though the differences are small in some cases. Prediction over a short term period incurs smaller prediction variability than over a long term period, as expected. The NN method tends to outperform other two methods. All the methods forecast an upward trend in all the four Canadian provinces for the period of August 12, 2020 to August 23, 2020, though the degree varies from method to method. This research offers model-based insights into the pandemic evolvement in Canada.
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245596

Abstract:
To meet the SDG requirement of spatial disaggregation of indicators, several methods have been developed to generate estimates of under-five mortality at the sub-national level. The reliability of sub-national mortality estimates in children aged 5-14 with the available survey data has not been evaluated so far. We generate Admin-1 sub-national estimates of the risk of dying in children aged less than five (5q0) and those aged 5 to 14 years old (10q5). We use 96 Demographic and Health Surveys (DHS) in 20 Sub-Saharan countries having at least 3 surveys designed to be representative at a sub-national level. The estimates account for the complex sample design of DHS and HIV-related biases in young children. A Bayesian space-time model previously developed for under-five mortality is used to smooth estimates across space and time in both age groups to reduce problems associated with data sparsity. The posterior distributions of the probability 10q5 are used to compute coefficients of variation and assess precision. Sufficiently precise estimates are retained to study the sub-national relationship between age-specific mortality rates (5q0 and 10q5), accounting for uncertainty in sub-national levels. Out of 1,132 space-time estimates, 62.3% are considered sufficiently precise with high heterogeneity across countries. Across all periods, sub-national estimates of mortality in children aged 0-4 are highly correlated with those in older children and young adolescents but this correlation is largely driven by the mortality decline. Within specific periods of time, it is often impossible to assess the relationship between mortality rates in the two age groups at the sub-national level, except in Nigeria, Ethiopia, Cameroon, Senegal and Zambia. As increased attention is devoted to survival after age 5, more research is needed to ensure that sub-national areas with specific interventions required for older children can be correctly identified.
Qinying Huang, Jinying Li
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245459

Abstract:
Background Although previously published meta-analyses have compared the surgical effects between the methods of Idiopathic epiretinal membrane (iERM) removal with or without ILM peeling, they did not reach an agreement. Purpose We aimed to provide more evidence for the treatment of iERM and whether additional ILM peeling was better or not by analyzing more updated studies and randomized control trials (RCTs). Method The search was conducted in Pubmed, Embase, Cochrane Library, Web of Science and Open Grey without language limitation and the studies included were from inception to December 2019. All studies of iERM with or without ILM peeling showed at least one of outcomes, such as best-corrected visual acuity (BCVA), central macular thickness (CMT) and recurrence of ERM. The pooled results between above groups were showed by the mean differences (MDs) and risk ratios (RR) with corresponding 95% confidence intervals (CIs). Result In total, 1645 eyes of five randomized controlled trials (RCTs) and fifteen retrospective studies were included. The short-term ( Conclusion By considering the risk of bias, we should determine whether ILM peeling is beneficial for short-term changes in BCVA in patients with iERM. Nevertheless, further studies are needed to confirm this. iERM removal without ILM peeling can improve the short-term decrease in CMT and ILM peeling decreases the recurrence of ERM, but the long-term changes in BCVA and CMT are similar with or without ILM peeling. There is a need for a true large scale randomized trial that will also include microperimetry and other functional measures.
Beza Jobira, Daniel N. Frank, Lori J. Silveira, Laura Pyle, Megan M. Kelsey, Yesenia Garcia-Reyes, Charles E. Robertson, Diana Ir, Kristen J. Nadeau, Melanie Cree-Green
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245219

Abstract:
Objective Hepatic steatosis (HS) is common in adolescents with obesity and polycystic ovary syndrome (PCOS). Gut microbiota are altered in adults with obesity, HS, and PCOS, which may worsen metabolic outcomes, but similar data is lacking in youth. Methods Thirty-four adolescents with PCOS and obesity underwent stool and fasting blood collection, oral glucose tolerance testing, and MRI for hepatic fat fraction (HFF). Fecal bacteria were profiled by high-throughput 16S rRNA gene sequencing. Results 50% had HS (N = 17, age 16.2±1.5 years, BMI 38±7 kg/m2, HFF 9.8[6.5, 20.7]%) and 50% did not (N = 17, age 15.8±2.2 years, BMI 35±4 kg/m2, HFF 3.8[2.6, 4.4]%). The groups showed no difference in bacterial α-diversity (richness p = 0.202; evenness p = 0.087; and diversity p = 0.069) or global difference in microbiota (β-diversity). Those with HS had lower % relative abundance (%RA) of Bacteroidetes (p = 0.013), Bacteroidaceae (p = 0.009), Porphyromonadaceae (p = 0.011), and Ruminococcaceae (p = 0.008), and higher Firmicutes:Bacteroidetes (F:B) ratio (47.8% vs. 4.3%, p = 0.018) and Streptococcaceae (p = 0.034). Bacterial taxa including phyla F:B ratio, Bacteroidetes, and family Bacteroidaceae, Ruminococcaceae and Porphyromonadaceae correlated with metabolic markers. Conclusions Obese adolescents with PCOS and HS have differences in composition of gut microbiota, which correlate with metabolic markers, suggesting a modifying role of gut microbiota in HS and PCOS.
Chloé L'Ecuyer-Sauvageau , Jérôme Dupras, Jie He, Jeoffrey Auclair, Charlène Kermagoret, Thomas G. Poder
Published: 19 January 2021
PLOS ONE, Volume 16; doi:10.1371/journal.pone.0245045

Abstract:
The lack of information on the value of ecosystems contributing to human well-being in urban and peri-urban setting is known to contribute to the degradation of natural capital and ecosystem services (ES). The purpose of this study was to determine the economic value of ES in Canada’s Capital Region (Ottawa-Gatineau region), so that these values can be integrated in future planning decisions. Using the valuation methods of market pricing, cost replacement, and two benefit transfer approaches (with adjustment and with meta-analysis), the value of 13 ES from five ecosystems (forests, wetlands, croplands, prairies and grasslands, and freshwater systems) was measured. The annual economic value of these 13 ES amounts to an average of 332 million dollars, and to a total economic value of over 5 billion dollars, annualized over 20 years. The largest part of this value is generated by nonmarket ES, indicating that much more emphasis should be put on the management, preservation, and understanding of processes that make up these types of ES. The work generated as part of this study is a first step towards operationalizing the concept of ES in planning. More specifically, these results can be used to raise awareness, but also as a stepping stone to improve ecosystem-wide planning in the Canada’s Capital Region.
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