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Tsuyoshi Watanabe, Satoshi Nagai, Yoko Kawakami, Taiga Asakura, Jun Kikuchi, Nobuharu Inaba, Yukiko Taniuchi, Hiroaki Kurogi, Seinen Chow, Tsutomu Tomoda, et al.
Scientific Reports, Volume 11, pp 1-16; doi:10.1038/s41598-021-84532-y

Abstract:
Eel larvae apparently feed on marine snow, but many aspects of their feeding ecology remain unknown. The eukaryotic 18S rRNA gene sequence compositions in the gut contents of four taxa of anguilliform eel larvae were compared with the sequence compositions of vertically sampled seawater particulate organic matter (POM) in the oligotrophic western North Pacific Ocean. Both gut contents and POM were mainly composed of dinoflagellates as well as other phytoplankton (cryptophytes and diatoms) and zooplankton (ciliophoran and copepod) sequences. Gut contents also contained cryptophyte and ciliophoran genera and a few other taxa. Dinoflagellates (family Gymnodiniaceae) may be an important food source and these phytoplankton were predominant in gut contents and POM as evidenced by DNA analysis and phytoplankton cell counting. The compositions of the gut contents were not specific to the species of eel larvae or the different sampling areas, and they were most similar to POM at the chlorophyll maximum in the upper part of the thermocline (mean depth: 112 m). Our results are consistent with eel larvae feeding on marine snow at a low trophic level, and feeding may frequently occur in the chlorophyll maximum in the western North Pacific.
, Taizo Matsumoto, Mari Isobe, Sadamu Kurono, Kaneko Yuka, , Jing-Ya Wang, , Kenji Kameda, , et al.
Scientific Reports, Volume 11, pp 1-13; doi:10.1038/s41598-021-84750-4

Abstract:
The morphology of the Golgi complex is influenced by the cellular context, which strictly correlates with nuclear functions; however, the mechanism underlying this association remains elusive. The inner nuclear membrane SUN proteins, SUN1 and SUN2, have diverse functions together with the outer nuclear membrane nesprin proteins, which comprise the LINC complex. We found that depletion of SUN1 leads to Golgi complex dispersion with maintenance of ministacks and retained function for vesicle transport through the Golgi complex. In addition, SUN2 associates with microtubule plus-end-directed motor KIF20A, possibly via nesprin-2. KIF20A plays a role in the Golgi dispersion in conjunction with the SUN2-nesprin-2 LINC complex in SUN1-depleted cells, suggesting that SUN1 suppresses the function of the SUN2-nesprin-2 LINC complex under a steady-state condition. Further, SUN1-knockout mice, which show impaired cerebellar development and cerebellar ataxia, presented altered Golgi morphology in Purkinje cells. These findings revealed a regulation of the Golgi organization by the LINC complex.
Shreyas Balachandran, Anatolii Polyanskii, Santosh Chetri, Pashupati Dhakal, Yi-Feng Su, Zu-Hawn Sung, Peter J. Lee
Scientific Reports, Volume 11, pp 1-12; doi:10.1038/s41598-021-84498-x

Abstract:
Elemental type-II superconducting niobium is the material of choice for superconducting radiofrequency cavities used in modern particle accelerators, light sources, detectors, sensors, and quantum computing architecture. An essential challenge to increasing energy efficiency in rf applications is the power dissipation due to residual magnetic field that is trapped during the cool down process due to incomplete magnetic field expulsion. New SRF cavity processing recipes that use surface doping techniques have significantly increased their cryogenic efficiency. However, the performance of SRF Nb accelerators still shows vulnerability to a trapped magnetic field. In this manuscript, we report the observation of a direct link between flux trapping and incomplete flux expulsion with spatial variations in microstructure within the niobium. Fine-grain recrystallized microstructure with an average grain size of 10–50 µm leads to flux trapping even with a lack of dislocation structures in grain interiors. Larger grain sizes beyond 100–400 µm do not lead to preferential flux trapping, as observed directly by magneto-optical imaging. While local magnetic flux variations imaged by magneto-optics provide clarity on a microstructure level, bulk variations are also indicated by variations in pinning force curves with sequential heat treatment studies. The key results indicate that complete control of the niobium microstructure will help produce higher performance superconducting resonators with reduced rf losses1 related to the magnetic flux trapping.
Jie Zhu, Anchi Wu, GuoYi Zhou
Scientific Reports, Volume 11, pp 1-8; doi:10.1038/s41598-021-84166-0

Abstract:
Phosphorus (P) is an important element in terrestrial ecosystems and plays a critical role in soil quality and ecosystem productivity. Soil total P distributions have undergone large spatial changes as a result of centuries of climate change. It is necessary to study the characteristics of the horizontal and vertical distributions of soil total P and its influencing factors. In particular, the influence of climatic factors on the spatial distribution of soil total P in China’s forest ecosystems remain relatively unknown. Here, we conducted an intensive field investigation in different forest ecosystems in China to assess the effect of climatic factors on soil total P concentration and distribution. The results showed that soil total P concentration significantly decreased with increasing soil depth. The spatial distribution of soil total P increased with increasing latitude and elevation gradient but decreased with increasing longitude gradient. Random forest models and linear regression analyses showed that the explanation rate of bioclimatic factors and their relationship with soil total P concentration gradually decreased with increasing soil depths. Variance partitioning analysis demonstrated that the most important factor affecting soil total P distribution was the combined effect of temperature and precipitation factor, and the single effect of temperature factors had a higher explanation rate compare with the single effect of precipitation factors. This work provides a new farmework for the geographic distribution pattern of soil total P and the impact of climate variability on P distribution in forest ecosystems.
Borja Herrero de la Parte, Mikel González-Arribas, Iñaki Diaz-Sanz, Teodoro Palomares, Ignacio García-Alonso
Scientific Reports, Volume 11, pp 1-9; doi:10.1038/s41598-021-85082-z

Abstract:
Partial hepatectomy (PHx) is the gold standard for the treatment of colorectal cancer liver metastases. However, after removing a substantial amount of hepatic tissue, growth factors are released to induce liver regeneration, which may promote the proliferation of liver micrometastases or circulating tumour cells still present in the patient. The aim of this study is to assess the effect of PHx on the growth of liver metastases induced by intrasplenic cell inoculation as well as on in vitro proliferation of the same cancer cell line. Liver tumours were induced in 18 WAG/RijHsd male rats, by seeding 250,000 syngeneic colorectal cancer cells (CC531) into the spleen. The left lateral lobe of the liver was mobilized and in half of the animals it was removed to achieve a 40% hepatectomy. Twenty-eight days after tumour induction, the animals were sacrificed and the liver was removed and sliced to assess the relative tumour surface area (RTSA%). CC531 cells were cultured in presence of foetal calf serum, non-hepatectomised (NRS) or hepatectomized rat serum (HRS), and their proliferation rate at 24, 48, and 72 h was measured. RTSA% was significantly higher in animals which had undergone PHx than in the controls (non-hepatectomised) (46.98 ± 8.76% vs. 18.73 ± 5.65%; p < 0.05). Analysing each lobe separately, this difference in favour of hepatectomized animals was relevant and statistically significant in the paramedian and caudate lobes. But in the right lobe the difference was scarce and not significant. In vitro, 2.5% HRS achieved stronger proliferative rates than the control cultures (10% FCS) or their equivalent of NRS. In this experimental model, a parallelism has been shown between the effect of PHx on the growth of colorectal cancer cells in the liver and the effect of the serum on those cells in vitro.
Peihuang Zhu, Yu Chen, Jinfeng Zhang, Fan Wu, Xiaofeng Wang, Ting Pan, Qiang Wei, Yanping Hao, Xuelian Chen, Chunwu Jiang, et al.
Scientific Reports, Volume 11, pp 1-11; doi:10.1038/s41598-021-84855-w

Abstract:
Transcription factors (TFs) play crucial regulatory roles in controlling the expression of the target genes in plants. APETALA2/Ethylene-responsive factors (AP2/ERF) are part of a large superfamily of plant-specific TFs whose members are involved in the control of plant metabolism, development and responses to various biotic and abiotic stresses. However, the AP2/ERF superfamily has not been identified systematically in Masson pine (Pinus massoniana), which is one of the most important conifer in southern China. Therefore, we performed systematic identification of the AP2/ERF superfamily using transcriptome sequencing data from Masson pine. In the current study, we obtained 88 members of the AP2/ERF superfamily. All PmAP2/ERF members could be classified into 3 main families, AP2 (7 members), RAV (7 members), ERF (73 members) families, and a soloist protein. Subcellular localization assays suggested that two members of PmAP2/ERF were nuclear proteins. Based on pine wood nematode (PWN) inoculated transcriptome and qPCR analysis, we found that many members of PmAP2/ERF could respond to PWN inoculation and PWN related treatment conditions in vitro. In general, members of the AP2/ERF superfamily play an important role in the response of Masson pine responds to PWN. Furthermore, the roles of the AP2/ERF superfamily in other physiological activities of Masson pine remain to be further studied.
Larissa Fernanda Garcia, Guilherme Portes Silva, Eliana Vera Geremia, Laura Beatriz Lima Goulart, Carlos Tadeu Dos Santos Dias, Sila Carneiro da Silva
Scientific Reports, Volume 11, pp 1-16; doi:10.1038/s41598-021-84844-z

Abstract:
In grasses, leaf expansion and central rib growth occur in a non-proportional manner, with potential implications to the nutritive value of leaves. The objective of this study was to evaluate the relationship among blade length, percentage of central rib, anatomical characteristics and the nutritive value along the length of leaf blades of different sizes and hierarchical order of insertion on the tiller axis of Napier elephant grass (Pennisetum purpureum Schum. cv. Napier). Two experiments were carried out with isolated growing plants during the summer of 2017 (January to March). Central rib mass increased linearly with the increase in leaf blade mass and its percentage relative to blade mass decreased from the base to the tip of the leaf. There were no significant variations in anatomical characteristics along the length of leaf blades when central rib was not taken into account. The central rib showed negative relationship with nutritive value. The apical portions of long leaves showed similar digestibility to short leaves. The multivariate analysis of Cluster and Principal Components grouped the response variables according to leaf hierarchical order, final blade length and percentage of structural tissues, highlighting the relationship between leaf size, structural tissues and nutritive value.
S. Carlos, E. Burgueño, A. Ndarabu, G. Reina, C. Lopez-Del Burgo, A. Osorio, B. Makonda, J. de Irala
Scientific Reports, Volume 11, pp 1-10; doi:10.1038/s41598-021-84839-w

Abstract:
Retention is a key element in HIV prevention programs. In Sub-Saharan Africa most data on retention come from HIV clinical trials or people living with HIV attending HIV treatment and control programs. Data from observational cohorts are less frequent. Retention at 6-/12-month follow-up and its predictors were analyzed in OKAPI prospective cohort. From April 2016 to April 2018, 797 participants aged 15–59 years attending HIV Voluntary Counseling and Testing in Kinshasa were interviewed about HIV-related knowledge and behaviors at baseline and at 6- and 12-month follow-ups. Retention rates were 57% and 27% at 6- and 12-month follow up; 22% of participants attended both visits. Retention at 6-month was significantly associated with 12-month retention. Retention was associated with low economic status, being studying, daily/weekly Internet access, previous HIV tests and aiming to share HIV test with partner. Contrarily, perceiving a good health, living far from an antiretroviral center, daily/weekly alcohol consumption and perceiving frequent HIV information were inversely associated with retention. In conclusion, a high attrition was found among people attending HIV testing participating in a prospective cohort in Kinshasa. Considering the low retention rates and the predictors found in this study, more HIV cohort studies in Kinshasa need to be evaluated to identify local factors and strategies that could improve retention if needed.
Ruoqian Lin, Rui Zhang, Chunyang Wang, Xiao-Qing Yang, Huolin L. Xin
Scientific Reports, Volume 11, pp 1-15; doi:10.1038/s41598-021-84499-w

Abstract:
Atom segmentation and localization, noise reduction and deblurring of atomic-resolution scanning transmission electron microscopy (STEM) images with high precision and robustness is a challenging task. Although several conventional algorithms, such has thresholding, edge detection and clustering, can achieve reasonable performance in some predefined sceneries, they tend to fail when interferences from the background are strong and unpredictable. Particularly, for atomic-resolution STEM images, so far there is no well-established algorithm that is robust enough to segment or detect all atomic columns when there is large thickness variation in a recorded image. Herein, we report the development of a training library and a deep learning method that can perform robust and precise atom segmentation, localization, denoising, and super-resolution processing of experimental images. Despite using simulated images as training datasets, the deep-learning model can self-adapt to experimental STEM images and shows outstanding performance in atom detection and localization in challenging contrast conditions and the precision consistently outperforms the state-of-the-art two-dimensional Gaussian fit method. Taking a step further, we have deployed our deep-learning models to a desktop app with a graphical user interface and the app is free and open-source. We have also built a TEM ImageNet project website for easy browsing and downloading of the training data.
Jide Tian, Min Song, Daniel L. Kaufman
Scientific Reports, Volume 11, pp 1-8; doi:10.1038/s41598-021-84751-3

Abstract:
Most multiple sclerosis (MS) patients given currently available disease-modifying drugs (DMDs) experience progressive disability. Accordingly, there is a need for new treatments that can limit the generation of new waves T cell autoreactivity that drive disease progression. Notably, immune cells express GABAA-receptors (GABAA-Rs) whose activation has anti-inflammatory effects such that GABA administration can ameliorate disease in models of type 1 diabetes, rheumatoid arthritis, and COVID-19. Here, we show that oral GABA, which cannot cross the blood–brain barrier (BBB), does not affect the course of murine experimental autoimmune encephalomyelitis (EAE). In contrast, oral administration of the BBB-permeable GABAA-R-specific agonist homotaurine ameliorates monophasic EAE, as well as advanced-stage relapsing–remitting EAE (RR-EAE). Homotaurine treatment beginning after the first peak of paralysis reduced the spreading of Th17 and Th1 responses from the priming immunogen to a new myelin T cell epitope within the CNS. Antigen-presenting cells (APC) isolated from homotaurine-treated mice displayed an attenuated ability to promote autoantigen-specific T cell proliferation. The ability of homotaurine treatment to limit epitope spreading within the CNS, along with its safety record, makes it an excellent candidate to help treat MS and other inflammatory disorders of the CNS.
Hyunmin Ko, Hyo Kee Kim, Chris Chung, Ahram Han, Seung-Kee Min, , Sangil Min
Scientific Reports, Volume 11, pp 1-9; doi:10.1038/s41598-021-84868-5

Abstract:
This study analyzed the association between medication adherence and the intrapatient variability (IPV) of tacrolimus concentrations among kidney transplant recipients through a post hoc analysis of the dataset from a recently conducted randomized controlled trial. Among 138 patients enrolled in the original trial, 92 patients with ≥ 5 months of medication event monitoring system (MEMS) use and ≥ 4 tacrolimus trough values were included in this post hoc analysis. The variability of tacrolimus trough levels was calculated using coefficient variation (CV) and mean absolute deviation. Adherence was assessed using MEMS and self-report via the Basal Assessment of Adherence to Immunosuppressive Medication Scale. There were no statistically significant differences in the CV [median 16.5% [interquartile range 11.6–25.5%] and 16.0% [11.5–23.5%], respectively, P = .602] between the nonadherent (n = 59) and adherent groups (n = 33). There was also no significant correlation between the CV and adherence detected by MEMS (taking adherence, ρ = − 0.067, P = .527; dosing adherence, ρ = − 0.098, P = .352; timing adherence, ρ = − 0.113, P = .284). Similarly, adherence measured by self-report did not significantly affect the IPV (P = .452). In this post hoc analysis, nonadherent behavior, measured through electronic monitoring or self-report, did not affect the IPV.
A. J. Webster, K. Gaitskell, I. Turnbull, B. J. Cairns, R. Clarke
Scientific Reports, Volume 11, pp 1-13; doi:10.1038/s41598-021-84860-z

Abstract:
The importance of quantifying the distribution and determinants of multimorbidity has prompted novel data-driven classifications of disease. Applications have included improved statistical power and refined prognoses for a range of respiratory, infectious, autoimmune, and neurological diseases, with studies using molecular information, age of disease incidence, and sequences of disease onset (“disease trajectories”) to classify disease clusters. Here we consider whether easily measured risk factors such as height and BMI can effectively characterise diseases in UK Biobank data, combining established statistical methods in new but rigorous ways to provide clinically relevant comparisons and clusters of disease. Over 400 common diseases were selected for analysis using clinical and epidemiological criteria, and conventional proportional hazards models were used to estimate associations with 12 established risk factors. Several diseases had strongly sex-dependent associations of disease risk with BMI. Importantly, a large proportion of diseases affecting both sexes could be identified by their risk factors, and equivalent diseases tended to cluster adjacently. These included 10 diseases presently classified as “Symptoms, signs, and abnormal clinical and laboratory findings, not elsewhere classified”. Many clusters are associated with a shared, known pathogenesis, others suggest likely but presently unconfirmed causes. The specificity of associations and shared pathogenesis of many clustered diseases provide a new perspective on the interactions between biological pathways, risk factors, and patterns of disease such as multimorbidity.
Aminata Camara, Salimata Konate, Maryam Tidjani Alou, Aly Kodio, Amadou Hamidou Togo, Sebastien Cortaredona, Bernard Henrissat, Mahamadou Ali Thera, Ogobara K. Doumbo, Didier Raoult, et al.
Scientific Reports, Volume 11, pp 1-11; doi:10.1038/s41598-021-84641-8

Abstract:
Gut microbial dysbiosis has been shown to be an instrumental factor in severe acute malnutrition (SAM) and particularly, the absence of Methanobrevibacter smithii, a key player in energy harvest. Nevertheless, it remains unknown whether this absence reflects an immaturity or a loss of the microbiota. In order to assess that, we performed a case–control study in Mali using a propensity score weighting approach. The presence of M. smithii was tested using quantitative PCR on faeces collected from SAM children at inclusion and at discharge when possible or at day 15 for controls. M. smithii was highly significantly associated with the absence of SAM, detected in 40.9% controls but only in 4.2% cases (p < 0.0001). The predictive positive value for detection of M. smithii gradually increased with age in controls while decreasing in cases. Among children providing two samples with a negative first sample, no SAM children became positive, while this proportion was 2/4 in controls (p = 0.0015). This data suggests that gut dysbiosis in SAM is not an immaturity but rather features a loss of M. smithii. The addition of M. smithii as a probiotic may thus represent an important addition to therapeutic approaches to restore gut symbiosis.
Natália Barbosa Tossini, André Luis Simões Zacharias, Luiza Souza Seraphim Abrantes, Paula Regina Mendes Da Silva Serrão
Scientific Reports, Volume 11, pp 1-6; doi:10.1038/s41598-021-85054-3

Abstract:
The objective of this study was to verify whether women in the initial stages of hand osteoarthritis (HOA) already have impaired grip strength and flexor and extensor torque of the wrist compared to healthy women. It also aimed to correlate these variables with pain, stiffness, and function of the hand. Twenty-six women were divided into a control group [CG, n = 13; 56 (51–61) years old] and a hand osteoarthritis group [HOAG, n = 13; 58 (53–63) years old]. Grades II and III were included in the HOA group according to the criteria of Kellgren and Lawrence. All volunteers answered an initial assessment form, the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire and the Australian/Canadian Hand Osteoarthritis Index (AUSCAN). The grip strength and isometric wrist flexor and extensor torque were evaluated by a hydraulic dynamometer. Comparisons between groups used Student’s t test for independent samples and the Mann–Whitney test. Spearman's correlation was used to correlate grip strength and flexor and extensor wrist torque to the degree of disease and DASH and AUSCAN scores. There were no differences between the groups in grip strength or flexor and extensor torque values. In terms of the DASH and the AUSCAN, the HOA group had higher scores, indicating worse hand function. A strong negative correlation was found between grip strength and the degree of HOA (r = − 0.70, p = 0.008), and a moderate positive correlation was found between flexor torque and the degree of HOA (r = 0.53, p = 0.05). The pain (r = − 0.61, p = 0.02) and function (r = − 0.66, p = 0.01) sections of the AUSCAN correlated negatively with grip strength. Pain can be an important feature in the HOA rehabilitation process, as it can influence handgrip strength and function. It is important that rehabilitation is implemented as soon as possible to guarantee the maintenance of strength and function since with the severity of the disease, patients tend to have deficits in grip strength and function.
B. Sartorius, A. B. Lawson, R. L. Pullan
Scientific Reports, Volume 11, pp 1-11; doi:10.1038/s41598-021-83780-2

Abstract:
COVID-19 caseloads in England have passed through a first peak, and at the time of this analysis appeared to be gradually increasing, potentially signalling the emergence of a second wave. To ensure continued response to the epidemic is most effective, it is imperative to better understand both retrospectively and prospectively the geographical evolution of COVID-19 caseloads and deaths at small-area resolution, identify localised areas in space–time at significantly higher risk, quantify the impact of changes in localised population mobility (or movement) on caseloads, identify localised risk factors for increased mortality and project the likely course of the epidemic at high spatial resolution in coming weeks. We applied a Bayesian hierarchical space–time SEIR model to assess the spatiotemporal variability of COVID-19 caseloads (transmission) and deaths at small-area scale in England [Middle Layer Super Output Area (MSOA), 6791 units] and by week (using observed data from week 5 to 34 of 2020), including key determinants, the modelled transmission dynamics and spatial–temporal random effects. We also estimate the number of cases and deaths at small-area resolution with uncertainty projected forward in time by MSOA (up to week 51 of 2020), the impact mobility reductions (and subsequent easing) have had on COVID-19 caseloads and quantify the impact of key socio-demographic risk factors on COVID-19 related mortality risk by MSOA. Reductions in population mobility during the course of the first lockdown had a significant impact on the reduction of COVID-19 caseloads across England, however local authorities have had a varied rate of reduction in population movement which our model suggest has substantially impacted the geographic heterogeneity in caseloads at small-area scale. The steady gain in population mobility, observed from late April, appears to have contributed to a slowdown in caseload reductions towards late June and subsequent start of the second wave. MSOA with higher proportions of elderly (70+ years of age) and elderly living in deprivation, both with very distinct geographic distributions, have a significantly elevated COVID-19 mortality rates. While non-pharmaceutical interventions (that is, reductions in population mobility and social distancing) had a profound impact on the trajectory of the first wave of the COVID-19 outbreak in England, increased population mobility appears to have significantly contributed to the second wave. A number of contiguous small-areas appear to be at a significant elevated risk of high COVID-19 transmission, many of which are also at increased risk for higher mortality rates. A geographically staggered re-introduction of intensified social distancing measures is advised and limited cross MSOA movement if the magnitude and geographic extent of the second wave is to be reduced.
Yuuki Iida, Kumiko Hongo, Takanobu Onoda, Yusuke Kita, Yukio Ishihara, Naoki Takabayashi, Ryo Kobayashi, Takeyuki Hiramatsu
Scientific Reports, Volume 11, pp 1-6; doi:10.1038/s41598-021-84885-4

Abstract:
Central venous port (CVP) is a widely used totally implantable venous access device. Recognition of risks associated with CVP-related complications is clinically important for safe, reliable, and long-term intravenous access. We therefore investigated factors associated with CVP infection and evulsion, including the device type. A total of 308 consecutive patients with initial CVP implantation between January 2011 and December 2017 were retrospectively reviewed, and the association of clinical features with CVP-related complications were analyzed. Intraoperative and postoperative complications occurred in 11 (3.6%) and 39 (12.7%) patients, respectively. The overall rate of CVP availability at six months was 91.4%. Malignancy and 2-Methacryloyloxyethyl phosphorylcholine (MPC) polymer-coated catheter use were negatively associated with the incidence of CVP infections. Accordingly, malignancy and MPC polymer-coated catheter use were independent predictors for lower CVP evulsion rate (odds ratio, 0.23 and 0.18, respectively). Furthermore, both factors were significantly associated with longer CVP availability (hazard ratio, 0.24 and 0.27, respectively). This retrospective study identified factors associated with CVP-related complications and long-term CVP availability. Notably, MPC polymer-coated catheter use was significantly associated with a lower rate of CVP infection and longer CVP availability, suggesting the preventive effect of MPC coating on CVP infection.
Kenji Kansaku
Scientific Reports, Volume 11, pp 1-3; doi:10.1038/s41598-021-85134-4

Abstract:
The impaired brain is often difficult to restore, owing to our limited knowledge of the complex nervous system. Accumulating knowledge in systems neuroscience, combined with the development of innovative technologies, may enable brain restoration in patients with nervous system disorders that are currently untreatable. The Neuroprosthetics in Systems Neuroscience and Medicine Collection provides a platform for interdisciplinary research in neuroprosthetics.
Yuyan You, Chao Bai, Xuefeng Liu, Maohua Xia, Yanqiang Yin, Yucun Chen, Wei Wang, Ting Jia, Yan Lu, Tianchun Pu, et al.
Scientific Reports, Volume 11, pp 1-7; doi:10.1038/s41598-021-84741-5

Abstract:
Cataracts are a common cause of visual impairment and blindness in mammals. They are usually associated with aging, but approximately one third of cases have a significant genetic component. Cataracts are increasingly prevalent among aging populations of captive giant pandas (Ailuropoda melanoleuca) and it is therefore important to identify genetic determinants that influence the likelihood of cataract development in order to distinguish between congenital and age-related disease. Here we screened for cataract-related genetic effects using a functional candidate gene approach combined with bioinformatics to identify the underlying genetic defect in a giant panda with congenital cataracts. We identified a missense mutation in exon 10 of the HSF4 gene encoding heat shock transcription factor 4. The mutation causes the amino acid substitution R377W in a highly conserved segment of the protein between the isoform-specific and downstream hydrophobic regions. Predictive modeling revealed that the substitution is likely to increase the hydrophobicity of the protein and disrupt interactions with spatially adjacent amino acid side chains. The mutation was not found in 13 unaffected unrelated animals but was found in an unrelated animal also diagnosed with senile congenital cataract. The novel missense mutation in the HSF4 gene therefore provides a potential new genetic determinant that could help to predict the risk of cataracts in giant pandas.
C. F. Lo
Scientific Reports, Volume 11, pp 1-9; doi:10.1038/s41598-021-84934-y

Abstract:
We have shown that the smallest possible singel-qubit critical coupling strength of the N-qubit two-photon Rabi model is only 1/N times that of the two-photon Rabi model. The spectral collapse can thus occur at a more attainable value of the critical coupling. For both of the two-qubit and three-qubit cases, we have also rigorously demonstrated that at the critical coupling the system not only has a set of discrete eigenenergies but also a continuous energy spectrum. The discrete eigenenergy spectrum can be derived via a simple one-to-one mapping to the bound state problem of a particle of variable effective mass in the presence of a finite potential well and a nonlocal potential. The energy difference of each qubit, which specifies both the depth of the finite potential well and the strength of the nonlocal potential, determines the number of bound states available, implying that the extent of the incomplete spectral collapse can be monitored in a straightforward manner.
F. C. Tilley, C. Arrondel, C. Chhuon, M. Boisson, N. Cagnard, M. Parisot, G. Menara, N. Lefort, I. C. Guerrera, C. Bole-Feysot, et al.
Scientific Reports, Volume 11, pp 1-13; doi:10.1038/s41598-021-84472-7

Abstract:
Several studies have reported WDR73 mutations to be causative of Galloway–Mowat syndrome, a rare disorder characterised by the association of neurological defects and renal-glomerular disease. In this study, we demonstrate interaction of WDR73 with the INTS9 and INTS11 components of Integrator, a large multiprotein complex with various roles in RNA metabolism and transcriptional control. We implicate WDR73 in two Integrator-regulated cellular pathways; namely, the processing of uridylate-rich small nuclear RNAs (UsnRNA), and mediating the transcriptional response to epidermal growth factor stimulation. We also show that WDR73 suppression leads to altered expression of genes encoding cell cycle regulatory proteins. Altogether, our results suggest that a range of cellular pathways are perturbed by WDR73 loss-of-function, and support the consensus that proper regulation of UsnRNA maturation, transcription initiation and cell cycle control are all critical in maintaining the health of post-mitotic cells such as glomerular podocytes and neurons, and preventing degenerative disease.
Chantal S. Parenteau, Edmund C. Lau, Ian C. Campbell, Amy Courtney
Scientific Reports, Volume 11, pp 1-11; doi:10.1038/s41598-021-84724-6

Abstract:
Identifying the prevalence of degenerative spinal pathologies and relevant demographic risk factors is important for understanding spine injury risk, prevention, treatment, and outcome, and for distinguishing acute injuries from degenerative pathologies. Prevalence data in the literature are often based on small-scale studies focused on a single type of pathology. This study evaluates the prevalence of diagnosis of selected degenerative spinal pathology diagnoses using Medicare insurance claim data in the context of published smaller-scale studies. In addition, the data are used to evaluate whether the prevalence is affected by age, sex, diagnosed obesity, and the use of medical imaging. The Medicare Claims 5% Limited Data Set was queried to identify diagnoses of degenerative spinal pathologies. Unique patient diagnoses per year were further evaluated as a function of age, gender, and obesity diagnosis. Participants were also stratified by coding for radiological imaging accompanying each diagnosis. The overall prevalence of diagnosed spinal degenerative disease was 27.3% and increased with age. The prevalence of diagnosed disc disease was 2.7 times greater in those with radiology. The results demonstrate that degenerative findings in the spine are common, and, since asymptomatic individuals may not receive a diagnosis of degenerative conditions, this analysis likely underestimates the general prevalence of these conditions.
Mehrdad Moshtaghi, Els Knaeps, Sindy Sterckx, Shungudzemwoyo Garaba, Dieter Meire
Scientific Reports, Volume 11, pp 1-12; doi:10.1038/s41598-021-84867-6

Abstract:
While at least 8 million tons of plastic litter are ending up in our oceans every year and research on marine litter detection is increasing, the spectral properties of wet as well as submerged plastics in natural marine environments are still largely unknown. Scientific evidence-based knowledge about these spectral characteristics has relevance especially to the research and development of future remote sensing technologies for plastic litter detection. In an effort to bridge this gap, we present one of the first studies about the hyperspectral reflectances of virgin and naturally weathered plastics submerged in water at varying suspended sediment concentrations and depth. We also conducted further analyses on the different polymer types such as Polyethylene terephthalate (PET), Polypropylene (PP), Polyester (PEST) and Low-density polyethylene (PE-LD) to better understand the effect of water absorption on their spectral reflectance. Results show the importance of using spectral wavebands in both the visible and shortwave infrared (SWIR) spectrum for litter detection, especially when plastics are wet or slightly submerged which is often the case in natural aquatic environments. Finally, we demonstrate in an example how to use the open access data set driven from this research as a reference for the development of marine litter detection algorithms.
Anton Starostin, Vladimir Strelnikov, Viktor Valtsifer, Irina Lebedeva, Irina Legchenkova, Edward Bormashenko
Scientific Reports, Volume 11, pp 1-11; doi:10.1038/s41598-021-84283-w

Abstract:
Omniphobic and icephobic twin-scale surfaces based on the “urchin”-like fluorinated Al2O3 particles are presented. Combined effect of hierarchical topography and fluorination supplied to the surfaces omniphobic and icephobic properties. The study of the stability of the Cassie wetting state is reported. High apparent contact angles were accompanied with the low contact angle hysteresis and high stability of the Cassie air trapping wetting state. Time delay of the ice crystallization as high as $$88\pm 5$$ 88 ± 5 min was established when compared to the ice formation on flat aluminum and non-fluorinated “urchin”-like surfaces. Crystallized water droplets formed on the reported nano-structured surfaces were easily blown out by the air jet with the velocity of $$v=3.0\pm 1.0$$ v = 3.0 ± 1.0 m/s, (which is markedly lower than that common for exploitation of aircrafts and turbines). Heated “urchin”-like surfaces completely restored their omniphobic and icephobic surfaces after thawing. Qualitative analysis of water freezing is supplied.
Egi Kardia, Michael Frese, Elena Smertina, Tanja Strive, Xi-Lei Zeng, Mary Estes, Robyn N. Hall
Scientific Reports, Volume 11, pp 1-12; doi:10.1038/s41598-021-84774-w

Abstract:
Organoids emulate many aspects of their parental tissue and are therefore used to study pathogen-host interactions and other complex biological processes. Here, we report a robust protocol for the isolation, maintenance and differentiation of rabbit small intestinal organoids and organoid-derived cell monolayers. Our rabbit intestinal spheroid and monolayer cultures grew most efficiently in L-WRN-conditioned medium that contained Wnt, R-spondin and Noggin, and that had been supplemented with ROCK and TGF-β inhibitors. Organoid and monolayer differentiation was initiated by reducing the concentration of the L-WRN-conditioned medium and by adding ROCK and Notch signalling inhibitors. Immunofluorescence staining and RT-qPCR demonstrated that our organoids contained enterocytes, enteroendocrine cells, goblet cells and Paneth cells. Finally, we infected rabbit organoids with Rabbit calicivirus Australia-1, an enterotropic lagovirus that—like many other caliciviruses—does not grow in conventional cell culture. Despite testing various conditions for inoculation, we did not detect any evidence of virus replication, suggesting either that our organoids do not contain suitable host cell types or that additional co-factors are required for a productive infection of rabbit organoids with Rabbit calicivirus Australia-1.
Lukas Otto, Petra Wolint, Annina Bopp, Anna Woloszyk, Anton S. Becker, Andreas Boss, Roland Böni, Maurizio Calcagni, Pietro Giovanoli, Simon P. Hoerstrup, et al.
Scientific Reports, Volume 11, pp 1-15; doi:10.1038/s41598-021-84123-x

Abstract:
Bone regeneration is a complex process and the clinical translation of tissue engineered constructs (TECs) remains a challenge. The combination of biomaterials and mesenchymal stem cells (MSCs) may enhance the healing process through paracrine effects. Here, we investigated the influence of cell format in combination with a collagen scaffold on key factors in bone healing process, such as mineralization, cell infiltration, vascularization, and ECM production. MSCs as single cells (2D-SCs), assembled into microtissues (3D-MTs) or their corresponding secretomes were combined with a collagen scaffold and incubated on the chicken embryo chorioallantoic membrane (CAM) for 7 days. A comprehensive quantitative analysis was performed on a cellular level by histology and by microcomputed tomography (microCT). In all experimental groups, accumulation of collagen and glycosaminoglycan within the scaffold was observed over time. A pronounced cell infiltration and vascularization from the interface to the surface region of the CAM was detected. The 3D-MT secretome showed a significant mineralization of the biomaterial using microCT compared to all other conditions. Furthermore, it revealed a homogeneous distribution pattern of mineralization deposits in contrast to the cell-based scaffolds, where mineralization was only at the surface. Therefore, the secretome of MSCs assembled into 3D-MTs may represent an interesting therapeutic strategy for a next-generation bone healing concept.
Angélina Trotereau, Claudine Boyer, Isabelle Bornard, Max Jean Bernard Pécheur, Catherine Schouler, Clara Torres-Barceló
Scientific Reports, Volume 11, pp 1-10; doi:10.1038/s41598-021-84305-7

Abstract:
Bacterial wilt caused by the Ralstonia solanacearum species complex (RSSC) is among the most important plant diseases worldwide, severely affecting a high number of crops and ornamental plants in tropical regions. Only a limited number of phages infecting R. solanacearum have been isolated over the years, despite the importance of this bacterium and the associated plant disease. The antibacterial effect or morphological traits of these R. solanacearum viruses have been well studied, but not their genomic features, which need deeper consideration. This study reports the full genome of 23 new phages infecting RSSC isolated from agricultural samples collected in Mauritius and Reunion islands, particularly affected by this plant bacterial pathogen and considered biodiversity hotspots in the Southwest Indian Ocean. The complete genomic information and phylogenetic classification is provided, revealing high genetic diversity between them and weak similarities with previous related phages. The results support our proposal of 13 new species and seven new genera of R. solanacearum phages. Our findings highlight the wide prevalence of phages of RSSC in infected agricultural settings and the underlying genetic diversity. Discoveries of this kind lead more insight into the diversity of phages in general and to optimizing their use as biocontrol agents of bacterial diseases of plants in agriculture.
Katharina Ernst, Ann-Katrin Mittler, Veronika Winkelmann, Carolin Kling, Nina Eberhardt, Anna Anastasia, Michael Sonnabend, Robin Lochbaum, Jan Wirsching, Moona Sakari, et al.
Scientific Reports, Volume 11, pp 1-17; doi:10.1038/s41598-021-84817-2

Abstract:
Whooping cough is caused by Bordetella pertussis that releases pertussis toxin (PT) which comprises enzyme A-subunit PTS1 and binding/transport B-subunit. After receptor-mediated endocytosis, PT reaches the endoplasmic reticulum from where unfolded PTS1 is transported to the cytosol. PTS1 ADP-ribosylates G-protein α-subunits resulting in increased cAMP signaling. Here, a role of target cell chaperones Hsp90, Hsp70, cyclophilins and FK506-binding proteins for cytosolic PTS1-uptake is demonstrated. PTS1 specifically and directly interacts with chaperones in vitro and in cells. Specific pharmacological chaperone inhibition protects CHO-K1, human primary airway basal cells and a fully differentiated airway epithelium from PT-intoxication by reducing intracellular PTS1-amounts without affecting cell binding or enzyme activity. PT is internalized by human airway epithelium secretory but not ciliated cells and leads to increase of apical surface liquid. Cyclophilin-inhibitors reduced leukocytosis in infant mouse model of pertussis, indicating their promising potential for developing novel therapeutic strategies against whooping cough.
Marie Shinohara, Hiroshi Arakawa, Yuuichi Oda, Nobuaki Shiraki, Shinji Sugiura, Takumi Nishiuchi, Taku Satoh, Keita Iino, Sylvia Leo, Yusuke Kato, et al.
Scientific Reports, Volume 11, pp 1-10; doi:10.1038/s41598-021-84861-y

Abstract:
Examining intestine–liver interactions is important for achieving the desired physiological drug absorption and metabolism response in in vitro drug tests. Multi-organ microphysiological systems (MPSs) constitute promising tools for evaluating inter-organ interactions in vitro. For coculture on MPSs, normal cells are challenging to use because they require complex maintenance and careful handling. Herein, we demonstrated the potential of coculturing normal cells on MPSs in the evaluation of intestine–liver interactions. To this end, we cocultured human-induced pluripotent stem cell-derived intestinal cells and fresh human hepatocytes which were isolated from PXB mice with medium circulation in a pneumatic-pressure-driven MPS with pipette-friendly liquid-handling options. The cytochrome activity, albumin production, and liver-specific gene expressions in human hepatocytes freshly isolated from a PXB mouse were significantly upregulated via coculture with hiPS-intestinal cells. Our normal cell coculture shows the effects of the interactions between the intestine and liver that may occur in vivo. This study is the first to demonstrate the coculturing of hiPS-intestinal cells and fresh human hepatocytes on an MPS for examining pure inter-organ interactions. Normal-cell coculture using the multi-organ MPS could be pursued to explore unknown physiological mechanisms of inter-organ interactions in vitro and investigate the physiological response of new drugs.
Hana Sonbol, Fuad Ameen, Sami AlYahya, Abobakr Almansob, Suaad Alwakeel
Scientific Reports, Volume 11, pp 1-19; doi:10.1038/s41598-021-84794-6

Abstract:
Green synthesized nanoparticles (NPs) have emerged as a new and promising alternative to overcome the drug resistance problem. Peculiar nano-specific features of palladium NPs (Pd-NPs) offer invaluable possibilities for clinical treatment. Due to the development of multi-drug resistance (MDR) in pathogenic bacteria and the prevalence of cancers, use of algae-mediated Pd-NPs could be a prospective substitute. Therefore, Pd-NPs were synthesized by a one-step, cost-effective, and environmentally friendly green method using the extract from a brown alga, Padina boryana (PB-extract), and evaluated for their antibacterial, antibiofilm, and anticancer activities. Pd-NPs were physicochemically characterized for size, shape, morphology, surface area, charge, atomic composition, crystal structure, and capping of Pd-NPs by PB-extract biomolecules by various techniques. The data revealed crystalline Pd-NPs with an average diameter of 8.7 nm, crystal size/structure of 11.16 nm/face-centered cubic, lattice d-spacing of 0.226 nm, 28.31% as atomic percentage, surface area of 16.1 m2/g, hydrodynamic size of 48 nm, and zeta-potential of − 28.7 ± 1.6 mV. Fourier-transform infrared spectroscopy (FT-IR) analysis revealed the role of PB-extract in capping of Pd-NPs by various functional groups such as –OH, C=C, C–O, and C–N from phenols, aliphatic hydrocarbons, aromatic rings, and aliphatic amine. Out of 31, 23 compounds were found involved in biosynthesis by Gas chromatography–mass spectrometry (GC–MS) analysis. Isolated strains were identified as MDR Staphylococcus aureus, Escherichia fergusonii, Acinetobacter pittii, Pseudomonas aeruginosa, Aeromonas enteropelogenes, and Proteus mirabilis and Pd-NPs exhibited strong antibacterial/antibiofilm activities against them with minimum inhibitory concentration (MIC) in the range of 62.5–125 μg/mL. Moreover, cell viability assays showed concentration-dependent anti-proliferation of breast cancer MCF-7 cells. Pd-NPs also enhanced mRNA expression of apoptotic marker genes in the order: p53 (5.5-folds) > bax (3.5-folds) > caspase-3 (3-folds) > caspase-9 (2-folds) at 125 μg/mL. This study suggested the possible role of PB-extract capped Pd-NPs for successful clinical management of MDR pathogens and breast cancer cells.
Hongxia Chen, Yanrong Guo, Hualing Wei, Xiaoyu Chen
Scientific Reports, Volume 11, pp 1-10; doi:10.1038/s41598-021-85077-w

Abstract:
Centralized intravenous admixture service (CIVAS) centres, which are pharmaceutical departments found in Chinese hospitals, provide high-quality intravenous fluids and pharmaceutical services for patients, and errors in their working procedures can lead to adverse consequences. Pharmacists, the primary CIVAS centre personnel, play a role in risk control; however, to date, the effect of pharmacists’ participation in risk management has not been reported. The main aim of this study was to evaluate the pharmacist’s role in risk control and evaluate its impact. A retrospective observational study was designed to assess the principal working process in the CIVAS centre of a provincial healthcare setting. Errors in the main working process were identified, and intervention measures were formulated. The pharmacist intervention effect was evaluated by assessing the identification rate of improper prescriptions; the incidence rate of drug preparation, compounding, packaging and delivery process errors; and expenditures on wasteful drugs. There was a higher identification rate for improper prescriptions after the intervention (P < 0.05), while the incidence of drug preparation (P < 0.05), admixture (P < 0.05), and packaging and delivery errors (P < 0.01) was significantly lower; the total wasteful medication expenditure was also dramatically reduced. The potential creativity of pharmacists in error control can provide dependable intravenous drugs for patients and reduce the running expenditures for CIVAS.
Susan Y. Jaconis, Alan J. E. Thompson, , Chiara Trimarchi, Nicola S. Cottee, ,
Scientific Reports, Volume 11, pp 1-14; doi:10.1038/s41598-021-84798-2

Abstract:
Improving the heat tolerance of cotton is a major concern for breeding programs. To address this need, a fast and effect way of quantifying thermotolerant phenotypes is required. Triphenyl tetrazolium chloride (TTC) based enzyme viability testing following high-temperature stress can be used as a vegetative heat tolerance phenotype. This is because when live cells encounter a TTC solution, TTC undergoes a chemical reduction producing a visible, insoluble red product called triphenyl formazan, that can be quantified spectrophotometrically. However, existing TTC based cell viability assays cannot easily be deployed at the scale required in a crop improvement program. In this study, a heat stress assay (HSA) based on the use of TTC enzyme viability testing has been refined and improved for efficiency, reliability, and ease of use through four experiments. Sampling factors that may influence assay results, such as leaf age, plant water status, and short-term cold storage, were also investigated. Experiments conducted in this study have successfully downscaled the assay and identified an optimal sampling regime, enabling measurement of large segregating populations for application in breeding programs. The improved HSA methodology is important as it is proposed that long-term improvements in cotton thermotolerance can be achieved through the concurrent selection of superior phenotypes based on the HSA and yield performance in hot environments. Additionally, a new way of interpreting both heat tolerance and heat resistance was developed, differentiating genotypes that perform well at the time of a heat stress event and those that maintain a similar performance level to a non-stressed control.
Correction
Hiroyuki Ito, Yoshiro Yamashita, Takeshi Tanaka, Masahiro Takaki, Minh Nhat Le, Lay-Myint Yoshida, Konosuke Morimoto
Scientific Reports, Volume 11, pp 1-2; doi:10.1038/s41598-021-85556-0

Abstract:
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Rachida Naciri, Meryeme Lahrir, Chahinez Benadis, Mohamed Chtouki, Abdallah Oukarroum
Scientific Reports, Volume 11, pp 1-10; doi:10.1038/s41598-021-84990-4

Abstract:
A hydroponic experiment was conducted to evaluate the role of potassium (K) in tomato plant growth exposed to cadmium (Cd) stress. In this work, the effects of three potassium nutrition regimes (155, 232 and 310 ppm of K) combined with Cd at different levels (0, 12 and 25 µM of CdCl2) on chlorophyll content index, root and shoot dry weights, root morphology, chlorophyll a fluorescence and translocation factor were analyzed. The results showed a negative effect of cadmium, at different concentrations, on all these parameters. However, optimization of K nutrition has shown promising results by limiting the negative effect of Cd. A positive effect of the high concentration of K (310 ppm) was observed on leaf chlorophyll content and chlorophyll a fluorescence compared to 232 and 155 ppm under Cd stress. K supply improved the electron transport at PSI side indicated by the increase in the amplitude of the I–P phase of OJIP transient. Also, K at a concentration of 310 ppm significantly reduced Cd translocation from root to shoot and improved root and shoot growth parameters in the presence of Cd. K supplementation can reduce the negative effect of Cd by improving photosynthesis and promoting chlorophyll synthesis. The optimization of nutrients composition and concentration might be a good strategy to reduce the impact of Cd on plant growth and physiology.
Alex Ross, Marcelo Muñoz, Benjamin H. Rotstein, Erik J. Suuronen, Emilio I. Alarcon
Scientific Reports, Volume 11, pp 1-10; doi:10.1038/s41598-021-84896-1

Abstract:
Rapid synthesis of nanomaterials in scalable quantities is critical for accelerating the discovery and commercial translation of nanoscale-based technologies. The synthesis of metal nanogold and silver in volumes larger than 100 mL is not automatized and might require of the use of harsh conditions that in most cases is detrimental for the production of nanoparticles with reproducible size distributions. In this work, we present the development and optimization of an open-access low-cost NanoParticle Flow Synthesis System (NPFloSS) that allows for the rapid preparation of volumes of up to 1 L of gold and silver nanoparticle aqueous solutions.
Wu Ding, Guodong Ruan, Yingli Lin, Jianming Zhu, Chuanjian Tu, Zhian Li
Scientific Reports, Volume 11, pp 1-8; doi:10.1038/s41598-021-84996-y

Abstract:
Marital status proved to be an independent prognostic factor for survival in patients with breast cancer. We therefore strove to explore the impact of dynamic changes in marital status on the prognosis of breast cancer patients. We selected patients meeting the eligibility criteria from the Surveillance, Epidemiology, and End Results cancer database. We then used multivariate Cox proportional hazard regression model to analyze the effect of dynamic changes in marital status on the prognosis of overall survival (OS) and breast cancer-specific special survival (BCSS). Compared with the patients in the Single–Single group and the divorced/separated/widowed–divorced/separated/widowed (DSW–DSW) group, patients in the Married–Married group were significantly associated with better BCSS (HR 1.13, 95% CI: 1.03–1.19, P < 0.001; HR 1.19, 95% CI: 1.14–1.25, P < 0.001, respectively) and OS (HR 1.25, 95% CI: 1.20–1.30, P < 0.001; HR 1.49, 95% CI: 1.45–1.54, P < 0.001, respectively). In contrast to the DSW–DSW group, the Single–Single group and the DSW–Married group showed similar BCSS (HR 0.98, 95% CI: 0.92–1.05, P = 0.660; HR 1.06, 95% CI: 0.97–1.15, P = 0.193, respectively) but better OS (HR 1.14, 95% CI: 1.09–1.19, P < 0.001; HR 1.32, 95% CI: 1.25–1.40, P < 0.001, respectively). Compared with the Single–Single group, the Single–Married group showed significantly better BCSS (HR 1.21, 95% CI: 1.07–1.36, P = 0.003) but no difference in OS (HR 1.08, 95% CI: 0.98–1.18, P = 0.102); In contrast to the Married–DSW group, the Married–Married group exhibited better BCSS (HR 1.11, 95% CI: 1.05–1.18, P < 0.001) and OS (HR 1.27, 95% CI: 1.22–1.32, P < 0.001). Our study demonstrated that, regardless of their previous marital status, married patients had a better prognosis than unmarried patients. Moreover, single patients obtained better survival outcomes than DSW patients. Therefore, it is necessary to proactively provide single and DSW individuals with appropriate social and psychological support that would benefit them.
Kazuta Yamashita, Kosaku Higashino, Hiroaki Hayashi, Kazuki Takegami, Fumio Hayashi, Yoshihiro Tsuruo, Koichi Sairyo
Scientific Reports, Volume 11, pp 1-10; doi:10.1038/s41598-021-85060-5

Abstract:
Ionizing radiation from Computed tomography (CT) examinations and the associated health risks are growing concerns. The purpose of this study was to directly measure individual organ doses during routine clinical CT scanning protocols and to evaluate how these measurements vary with scanning conditions. Optically stimulated luminescence (OSL) dosimeters were surgically implanted into individual organs of fresh non-embalmed whole-body cadavers. Whole-body, head, chest, and abdomen CT scans were taken of 6 cadavers by simulating common clinical methods. The dosimeters were extracted and the radiation exposure doses for each organ were calculated. Average values were used for analysis. Measured individual organ doses for whole-body routine CT protocol were less than 20 mGy for all organs. The measured doses of surface/shallow organs were higher than those of deep organs under the same irradiation conditions. At the same tube voltage and tube current, all internal organ doses were significantly higher for whole-body scans compared with abdominal scans. This study could provide valuable information on individual organ doses and their trends under various scanning conditions. These data could be referenced and used when considering CT examination in daily clinical situations.
Hamza Amine, Yacir Benomar, Mohammed Taouis
Scientific Reports, Volume 11, pp 1-12; doi:10.1038/s41598-021-85018-7

Abstract:
Saturated fatty acids such as palmitic acid promote inflammation and insulin resistance in peripheral tissues, contrasting with the protective action of polyunsaturated fatty acids such docosahexaenoic acid. Palmitic acid effects have been in part attributed to its potential action through Toll-like receptor 4. Beside, resistin, an adipokine, also promotes inflammation and insulin resistance via TLR4. In the brain, palmitic acid and resistin trigger neuroinflammation and insulin resistance, but their link at the neuronal level is unknown. Using human SH-SY5Yneuroblastoma cell line we show that palmitic acid treatment impaired insulin-dependent Akt and Erk phosphorylation whereas DHA preserved insulin action. Palmitic acid up-regulated TLR4 as well as pro-inflammatory cytokines IL6 and TNFα contrasting with DHA effect. Similarly to palmitic acid, resistin treatment induced the up-regulation of IL6 and TNFα as well as NFκB activation. Importantly, palmitic acid potentiated the resistin-dependent NFkB activation whereas DHA abolished it. The recruitment of TLR4 to membrane lipid rafts was increased by palmitic acid treatment; this is concomitant with the augmentation of resistin-induced TLR4/MYD88/TIRAP complex formation mandatory for TLR4 signaling. In conclusion, palmitic acid increased TLR4 expression promoting resistin signaling through TLR4 up-regulation and its recruitment to membrane lipid rafts.
Kenji Goya, Akira Mori, Shigeki Tokita, Ryo Yasuhara, Tetsuo Kishi, Yoshiaki Nishijima, Setsuhisa Tanabe, Hiyori Uehara
Scientific Reports, Volume 11, pp 1-8; doi:10.1038/s41598-021-84950-y

Abstract:
Er3+/Dy3+ co-doped double-clad ZBLAN optical fiber has been used to obtain amplified spontaneous emission (ASE) broadband light sources cladding-pumped by 980-nm multimode laser diode (LD) sources. It has been demonstrated that mid-infrared broadband emission extending from 2515 to 3735 nm was obtained by energy transfer between Er3+ and Dy3+. We experimentally investigated the optimum design of Er3+/Dy3+ co-doped ZBLAN fiber in terms of ion concentration, fiber length, pumping configuration, and pumping power. The ASE output power was more than 2.5 mW when the LD pump power was set at 5 W. To assess its potential for gas sensing applications, the fabricated ASE light source was used to successfully detect methane gas with concentrations at 1% and 5%. The simple and stable construction of our ASE light source is suitable for practical purposes.
, Mina Mesri
Scientific Reports, Volume 11, pp 1-9; doi:10.1038/s41598-021-84266-x

Abstract:
This study examined the trends and patterns of major trauma (MT) activities, causes, mortality and survival at the Aintree Major Trauma Centre (MTC), Liverpool, between 2011 and 2018. The number of trauma team activations (TTAs) rose sharply over time (n = 699 in 2013; n = 1522 in 2018). The proportion of TTAs that involved MT patients decreased from 75.1% in 2013 to 67.4% in 2018. The leading cause of MT was a fall from less than 2 m (36%). There has been a fivefold increase in the overall number of trauma procedures between 2011 and 2018. Orthopaedic surgeons have performed 80% of operations (n = 7732), followed by neurosurgeons, oral and maxillofacial surgeons, and general trauma surgeons. Both types of fall (> 2 m and < 2 m) and road traffic accidents were the three leading causes of death during the study period. The observed mortality rates exceeded that of expected rates in years 2012, 2014, 2016 and 2017. The all-cause observed to expected mortality ratio was 1.08 between 2012 and 2018. A change in care for MT patients was not directly associated with improved survival, although the marginally ascending trend line in survival rates between 2012 and 2018 reflects a gradual positive change.
Tun-Wei Hsu, Jong-Ling Fuh, Da-Wei Wang, Li-Fen Chen, Chia-Jung Chang, Wen-Sheng Huang, Hsiu-Mei Wu, Wan-Yuo Guo
Scientific Reports, Volume 11, pp 1-12; doi:10.1038/s41598-021-84722-8

Abstract:
Dementia is related to the cellular accumulation of β-amyloid plaques, tau aggregates, or α-synuclein aggregates, or to neurotransmitter deficiencies in the dopaminergic and cholinergic pathways. Cellular and neurochemical changes are both involved in dementia pathology. However, the role of dopaminergic and cholinergic networks in metabolic connectivity at different stages of dementia remains unclear. The altered network organisation of the human brain characteristic of many neuropsychiatric and neurodegenerative disorders can be detected using persistent homology network (PHN) analysis and algebraic topology. We used 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging data to construct dopaminergic and cholinergic metabolism networks, and used PHN analysis to track the evolution of these networks in patients with different stages of dementia. The sums of the network distances revealed significant differences between the network connectivity evident in the Alzheimer’s disease and mild cognitive impairment cohorts. A larger distance between brain regions can indicate poorer efficiency in the integration of information. PHN analysis revealed the structural properties of and changes in the dopaminergic and cholinergic metabolism networks in patients with different stages of dementia at a range of thresholds. This method was thus able to identify dysregulation of dopaminergic and cholinergic networks in the pathology of dementia.
Victoria S. Zucherato, Leticia B. C. Penariol, Lilian E. C. M. Silva, Cristiana C. Padovan, Omero B. Poli-Neto, Julio C. Rosa-E-Silva, Rui A. Ferriani, Juliana Meola
Scientific Reports, Volume 11, pp 1-10; doi:10.1038/s41598-021-84884-5

Abstract:
It has been suggested that menstrual blood-derived mesenchymal stem/stromal cells (MenMSCs) are associated with the etiopathogenesis of endometriosis and considerable effort has been invested in searching for target genes and deciphering associated molecular pathways. However, reference gene stability for proper reproducible normalization in the analyses of the expression data validation is still unexplored in this experimental context. Therefore, in this exploratory study, we used stringent case and control selection criteria and collected menstrual blood from women with a laparoscopic diagnosis of advanced endometriosis and from fertile women without endometriosis. We tested for the first time the stability of 32 candidate reference genes to achieve increased accuracy and reliable results in the quantification of gene expression and direct future experiments using reverse transcription-quantitative PCR (RT-qPCR) in MenMSCs for endometriosis studies. Using the RefFinder web tool, we recommend the EIF2B1 and POP4 reference genes for the normalization of RT-qPCR data in study designs similar to ours. Furthermore, we suggest avoiding the commonly used GAPDH and ACTB reference genes as they are unstable. This high-visibility study is capable of directing different experimental designs as MenMSCs are derived from a minimally invasive tissue source with multifunctional roles in regenerative medicine.
Shuqi Zhang, Qing Wang, Rui Yang, Chuang Dong
Scientific Reports, Volume 11, pp 1-9; doi:10.1038/s41598-021-84917-z

Abstract:
The phase-type of a stainless steel is generally predicted by equivalent equations in terms of a major austenitic (γ) or ferritic (α) stabilizer Ni or Cr. The present paper attempts to understand the equivalent methods in stainless steels via the slopes of the phase boundary lines separating γ and γ + α phase zones. The prevailing equivalent coefficients are well interpreted using the slope ratios of the alloying elements divided by that of Ni or Cr, after analyzing over one hundred common stainless steels. Different from traditional composition equivalents which evaluate γ stabilizers and α stabilizers separately; the new equivalent scheme provides a unified phase stabilizing parameter for all alloying elements in stainless steels. This parameter is defined as γ stabilizing efficiency. Its negative or positive sign indicates γ stabilizer or α stabilizer, and its value represents the stabilizing efficiency.
Samyah Alanazi, Naif Alenzi, Fouza Alenazi, Hajera Tabassum, David Watson
Scientific Reports, Volume 11, pp 1-9; doi:10.1038/s41598-021-84717-5

Abstract:
Propolis, is a gummy material produced by honey bees from different parts of plants and is enriched with varied biological active compounds like flavonoids, phenolics and phenolic acids with wide applicability in the food, pharmaceutical and cosmetics industries. The current report is focused on the characterisation of propolis collected from Asir region, South-west of Saudi Arabia and its effect on Trypanosoma brucei (the causative organism of African sleeping sickness) and cytotoxic effect against U937 human leukemia cells. The Chemical composition and spectral characteristics of Saudi propolis was studied by Liquid Chromatography Mass Spectrometry (LC–MS) and High-performance liquid chromatography–evaporative light scattering detector (HPLC–ELSD).The two main active compounds isolated from Saudi propolis via column chromatography and size exclusion chromatography were fisetinidol and ferulic acid. High resolution electrospray ionization–mass spectrophotometer (HRESI–MS) and nuclear magnetic resonance (NMR) were used to elucidate the structures of the isolated compounds. All crudes extracts, fractions as well as isolated compounds were subjected for biological testing against Trypanosoma brucei (S427 WT), and their cytotoxicity against U937 human leukemia cells. Amongst the various samples investigated, S-6 fraction demonstrated highest anti-trypanosomal activity at 2.4 µg/ml MIC followed by fisetinidol at 4.7 µg/ml reflecting that the anti-trypanosomal activity is attributable to the presence of fisetinidol in the fraction. Similarly, all the tested samples exhibited cytotoxicity with an IC50 > 60 µg/ml. S-6 fractions exhibited highest cytotoxic activity against U937 cells with an IC50 of 58.7 µg/ml followed by ferulic acid with an IC50 87.7 µg/ml indicating that the cytotoxic effect of propolis might be due to the presence of ferulic acid. In conclusion, the biological activity of propolis could be attributed to the synergistic action of the two active compounds-ferulic acid and fisetinidol. The data obtained in the study is thus indicative of the role of propolis as potential anti-trypanosomal and anticancer agent for effective cancer therapy.
David J. Messmer, Ray T. Alisauskas, Hannu Pöysä, Pentti Runko, Robert G. Clark
Scientific Reports, Volume 11, pp 1-10; doi:10.1038/s41598-021-84160-6

Abstract:
Plasticity for breeding dates may influence population vulnerability to climate change via phenological mismatch between an organism’s life cycle requirements and resource availability in occupied environments. Some life history traits may constrain plasticity, however there have been remarkably few comparisons of how closely-related species, differing in key traits, respond to common phenology gradients. We compared population- and individual-level plasticity in clutch initiation dates (CID) in response to spring temperature among five duck species with early- to late-season nesting life histories. Plasticity was strongest in females of the earliest breeding species (common goldeneye [Bucephala clangula], mallard [Anas platyrhynchos], and gadwall [Mareca strepera]), whereas late-nesting lesser scaup (Aythya affinis) and white-winged scoter (Melanitta fusca deglandi) did not respond. These results contrast with previous work in other bird families that suggested late-breeders are generally more flexible. Nevertheless, late-breeding species exhibited annual variation in mean CID, suggesting response to other environmental factors unrelated to spring temperature. Goldeneye and gadwall females varied in their strength of individual plasticity (‘individual × environment’ interactions) and goldeneye and scoter females showed evidence of interannual repeatability of CID. Fitness consequences of CID plasticity in response to spring phenology, including trophic mechanisms and population consequences, warrant investigation.
Andrea Delli Pizzi, Antonio Maria Chiarelli, , Martina D’Annibale, Pierpaolo Croce, Consuelo Rosa, Domenico Mastrodicasa, Stefano Trebeschi, Doenja Marina Johanna Lambregts, Daniele Caposiena, et al.
Scientific Reports, Volume 11, pp 1-11; doi:10.1038/s41598-021-84816-3

Abstract:
Neoadjuvant chemo-radiotherapy (CRT) followed by total mesorectal excision (TME) represents the standard treatment for patients with locally advanced (≥ T3 or N+) rectal cancer (LARC). Approximately 15% of patients with LARC shows a complete response after CRT. The use of pre-treatment MRI as predictive biomarker could help to increase the chance of organ preservation by tailoring the neoadjuvant treatment. We present a novel machine learning model combining pre-treatment MRI-based clinical and radiomic features for the early prediction of treatment response in LARC patients. MRI scans (3.0 T, T2-weighted) of 72 patients with LARC were included. Two readers independently segmented each tumor. Radiomic features were extracted from both the “tumor core” (TC) and the “tumor border” (TB). Partial least square (PLS) regression was used as the multivariate, machine learning, algorithm of choice and leave-one-out nested cross-validation was used to optimize hyperparameters of the PLS. The MRI-Based “clinical-radiomic” machine learning model properly predicted the treatment response (AUC = 0.793, p = 5.6 × 10–5). Importantly, the prediction improved when combining MRI-based clinical features and radiomic features, the latter extracted from both TC and TB. Prospective validation studies in randomized clinical trials are warranted to better define the role of radiomics in the development of rectal cancer precision medicine.
Maria Reva, David A. DiGregorio, Denis S. Grebenkov
Scientific Reports, Volume 11, pp 1-17; doi:10.1038/s41598-021-84340-4

Abstract:
Synaptic transmission between neurons is governed by a cascade of stochastic calcium ion reaction–diffusion events within nerve terminals leading to vesicular release of neurotransmitter. Since experimental measurements of such systems are challenging due to their nanometer and sub-millisecond scale, numerical simulations remain the principal tool for studying calcium-dependent neurotransmitter release driven by electrical impulses, despite the limitations of time-consuming calculations. In this paper, we develop an analytical solution to rapidly explore dynamical stochastic reaction–diffusion problems based on first-passage times. This is the first analytical model that accounts simultaneously for relevant statistical features of calcium ion diffusion, buffering, and its binding/unbinding reaction with a calcium sensor for synaptic vesicle fusion. In particular, unbinding kinetics are shown to have a major impact on submillisecond sensor occupancy probability and therefore cannot be neglected. Using Monte Carlo simulations we validated our analytical solution for instantaneous calcium influx and that through voltage-gated calcium channels. We present a fast and rigorous analytical tool that permits a systematic exploration of the influence of various biophysical parameters on molecular interactions within cells, and which can serve as a building block for more general cell signaling simulators.
Shirley Yuk-Wah Liu, Vincent Wai-Sun Wong, Simon Kin-Hung Wong, Grace Lai-Hung Wong, Carol Man-Sze Lai, Candice Chuen-Hing Lam, Sally She-Ting Shu, Henry Lik-Yuen Chan, Enders Kwok-Wai Ng
Scientific Reports, Volume 11, pp 1-11; doi:10.1038/s41598-021-83782-0

Abstract:
Liver stiffness measurement (LSM) by transient elastography (TE) is a non-invasive assessment for diagnosing and staging liver fibrosis in non-alcoholic fatty liver disease (NAFLD). Evidence on its role as a longitudinal monitoring tool is lacking. This study aims to evaluate the role of TE in monitoring NAFLD improvement following bariatric surgery. This study prospectively recruited 101 morbidly obese patients undergoing laparoscopic bariatric surgery for intraoperative liver biopsy. Thirty-seven patients of the cohort received perioperative TE. Postoperative anthropometric, biochemical and LSM data were collected annually for 5 years. In 101 patients receiving liver biopsy (mean age 40.0 ± 10.3 years, mean body-mass-index (BMI) 40.0 ± 5.7 kg/m2), NASH and liver fibrosis were diagnosed in 42 (41.6%) and 48 (47.5%) patients respectively. There were 29 (28.7%) stage 1, 11 (10.9%) stage 2, 7 (6.9%) stage 3, and 1 (1.0%) stage 4 fibrosis. In 37 patients receiving TE (mean age 38.9 ± 10.8 years, mean BMI 41.1 ± 5.6 kg/m2), the percentages of total weight loss were 21.1 ± 7.6% at 1 year, 19.7 ± 8.3% at 3 years, and 17.1 ± 7.0% at 5 years after surgery. The mean LSM reduced significantly from 9.8 ± 4.6 kPa at baseline to 6.9 ± 3.4 kPa at 1 year, 7.3 ± 3.0 kPa at 3 years, and 6.8 ± 2.6 kPa at 5 years (P = 0.002). Using pre-defined LSM cut-offs, the rates of significant fibrosis, advanced fibrosis and cirrhosis being ruled out at 5 years improved from baseline values of 43.7 to 87.5% (P < 0.001), 56.8 to 91.7% (P < 0.001), and 64.9 to 91.7% (P < 0.001), respectively. TE was a useful monitoring tool in demonstrating the improvement of liver fibrosis following bariatric surgery.
Omid Norouzi, S. E. M. Pourhosseini, Hamid Reza Naderi, Francesco Di Maria, Animesh Dutta
Scientific Reports, Volume 11, pp 1-13; doi:10.1038/s41598-021-84979-z

Abstract:
Two state-of-the-art electrodes were successfully synthesized and used to assemble both symmetric and asymmetric type supercapacitors. 3DFAB was fabricated by direct pyrolysis of green macroalgae in the presence of NaOH. Possible NaOH activation mechanisms are proposed, which explains the formation of oxygen functional groups through quick penetration of OH- and NaOH into the vacancies. To obtain CoTLM, the tile-like architecture of cobalt oxides was introduced to the 3D interconnected functional algal biochar (3DFAB) by a simple one-pot hydrothermal method under mild conditions. For the symmetric supercapacitors, the maximum specific capacitance of RAB, 3DFAB, and CoTLM were 158, 296, and 445 F g−1 at the current density of 1 A g−1. Regarding cobalt-based asymmetric systems, the maximum capacitance for the 3DFAB//CoTLM was 411 F g−1. This asymmetric supercapacitor device also retained 100.9% of its initial capacitance after 4000 cycles at the current density of 4 A g−1. Unbuffered aqueous electrolyte and the unique morphological structure used in this study might catapult forward commercialization of such advanced energy storage devices.
Van Hien-Hoang, Nak-Kwan Chung, Heon-Jung Kim
Scientific Reports, Volume 11, pp 1-10; doi:10.1038/s41598-021-84736-2

Abstract:
The Kondo effect has been a topic of intense study because of its significant contribution to the development of theories and understanding of strongly correlated electron systems. In this work, we show that the Kondo effect is at work in La1−x Pr x NiO3−δ (0 ≤ x ≤ 0.6) thin films. At low temperatures, the local magnetic moments of the 3d e g electrons in Ni2+, which form because of oxygen vacancies, interact strongly with itinerant electrons, giving rise to an upturn in resistivity with x ≥ 0.2. Observation of negative magnetoresistance, described by the Khosla and Fisher model, further supports the Kondo picture. This case represents a rare example of the Kondo effect, where Ni2+ acts as an impurity in the background of Ni3+. We suggest that when Ni2+ does not participate in the regular lattice, it provides the local magnetic moments needed to scatter the conduction electrons in the Kondo effect. These results offer insights into emergent transport behaviors in metallic nickelates with mixed Ni3+ and Ni2+ ions, as well as structural disorder.
David Serrano, Ainara Cortés-Avizanda, Iñigo Zuberogoitia, Guillermo Blanco, José Ramón Benítez, Cecile Ponchon, Juan Manuel Grande, Olga Ceballos, Jon Morant, Eneko Arrondo, et al.
Scientific Reports, Volume 11, pp 1-13; doi:10.1038/s41598-021-84811-8

Abstract:
Natal dispersal, the movement between the birth and the first breeding site, has been rarely studied in long-lived territorial birds with a long-lasting pre-breeding stage. Here we benefited from the long-term monitoring programs of six populations of Egyptian vultures (Neophron percnopterus) from Spain and France to study how the rearing environment determines dispersal. For 124 vultures, we recorded a median dispersal distance of 48 km (range 0–656 km). Linear models were used to assess the effect of population and individual traits on dispersal distance at two spatial scales. Dispersal distances were inversely related to vulture density in the natal population, suggesting that birds perceive the abundance of conspecifics as a signal of habitat quality. This was particularly true for declining populations, so increasing levels of opportunistic philopatry seemed to arise in high density contexts as a consequence of vacancies created by human-induced adult mortality. Females dispersed further than males, but males were more sensitive to the social environment, indicating different dispersal tactics. Both sexes were affected by different individual attributes simultaneously and interactively with this social context. These results highlight that complex phenotype-by-environment interactions should be considered for advancing our understanding of dispersal dynamics in long-lived organisms.
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