bluuebunny/crossref_metadata_2025 huggingface dataset:
Do environmental risk factors for the development of psychosis distribute differently across dimensionally assessed psychotic experiences?
Authors: Cosgrave Jan , Purple Ross J. , Haines Ross , Porcheret Kate , van Heugten-van der Kloet Dalena , Johns Louise , Alexander Iona , Goodwin Guy M. , Foster Russell G. , Wulff Katharina
Published: April 2021

Psychotic experiences (PE) are associated with poorer functioning, higher distress and the onset of serious mental illness. Environmental exposures (e.g. childhood abuse) are associated with the development of PE. However, which specific exposures convey risk for each type or dimension of PE has rarely been explored. The Oxford Wellbeing Life and Sleep (OWLS) survey includes 22 environmental risk factors for psychosis and was designed to examine how environmental risks are associated with specific dimensions of PE. Multivariate logistic regression models were fit using these risk factors to predict six dimensions of PE (perceptual abnormalities, persecutory ideation, bizarre ideas, cognitive disorganisation, delusional mood and negative symptoms). Models were built using only 70% of the data, and then fit to the remaining data to assess their generalisability and quality. 1789 (27.2% men; mean age = 27.6; SD = 10.9) survey responses were analysed. The risk factors predictive of the most PE were anxiety, social withdrawal during childhood and trauma. Cannabis and depression predicted three dimensions with both predicting bizarre ideas and persecutory ideation. Psychological abuse and sleep quality each predicted two dimensions (persecutory ideation and delusional mood). Risk factors predicting one PE dimension were age (predicting cognitive disorganisation), physical abuse (bizarre ideas), bullying and gender (persecutory ideation); and circadian phase (delusional mood). These results lend support for a continuum of psychosis, suggesting environmental risks for psychotic disorders also increase the risk of assorted dimensions of PE. Furthermore, it advocates the use of dimensional approaches when examining environmental exposures for PE given that environmental risks distribute differently across dimensions.
Utilization of machine learning for identifying symptom severity military-related PTSD subtypes and their biological correlates
Authors: Siegel Carole E. , Laska Eugene M. , Lin Ziqiang , Xu Mu , Abu-Amara Duna , Jeffers Michelle K. , Qian Meng , Milton Nicholas , Flory Janine D. , Hammamieh Rasha , Daigle Bernie J. , Gautam Aarti , Dean Kelsey R. , Reus Victor I. , Wolkowitz Owen M. , Mellon Synthia H. , Ressler Kerry J. , Yehuda Rachel , Wang Kai , Hood Leroy , Doyle Francis J. , Jett Marti , Marmar Charles R.
Published: April 2021

We sought to find clinical subtypes of posttraumatic stress disorder (PTSD) in veterans 6–10 years post-trauma exposure based on current symptom assessments and to examine whether blood biomarkers could differentiate them. Samples were males deployed to Iraq and Afghanistan studied by the PTSD Systems Biology Consortium: a discovery sample of 74 PTSD cases and 71 healthy controls (HC), and a validation sample of 26 PTSD cases and 36 HC. A machine learning method, random forests (RF), in conjunction with a clustering method, partitioning around medoids, were used to identify subtypes derived from 16 self-report and clinician assessment scales, including the clinician-administered PTSD scale for DSM-IV (CAPS). Two subtypes were identified, designated S1 and S2, differing on mean current CAPS total scores: S2 = 75.6 (sd 14.6) and S1 = 54.3 (sd 6.6). S2 had greater symptom severity scores than both S1 and HC on all scale items. The mean first principal component score derived from clinical summary scales was three times higher in S2 than in S1. Distinct RFs were grown to classify S1 and S2 vs. HCs and vs. each other on multi-omic blood markers feature classes of current medical comorbidities, neurocognitive functioning, demographics, pre-military trauma, and psychiatric history. Among these classes, in each RF intergroup comparison of S1, S2, and HC, multi-omic biomarkers yielded the highest AUC-ROCs (0.819–0.922); other classes added little to further discrimination of the subtypes. Among the top five biomarkers in each of these RFs were methylation, micro RNA, and lactate markers, suggesting their biological role in symptom severity.
Contribution of growth hormone secretagogue receptor (GHSR) signaling in the ventral tegmental area (VTA) to the regulation of social motivation in male mice
Authors: Park Su-Bin , King Samantha , MacDonald David , Wilson Anne , MacKay Harry , Woodside Barbara , Abizaid Alfonso
Published: April 2021

Most psychiatric disorders are characterized by deficits in the ability to interact socially with others. Ghrelin, a hormone normally associated with the regulation of glucose utilization and appetite, is also implicated in the modulation of motivated behaviors including those associated with food and sex rewards. Here we hypothesized that deficits in ghrelin receptor (growth hormone secretagogue receptor; GHSR) signaling are also associated with deficits in social motivation in male mice. To test this hypothesis, we compared social motivation in male mice lacking GHSR or mice treated with the GHSR antagonist JMV2959 with that of WT or vehicle-treated mice. GHSR signaling in dopamine cells of the ventral tegmental area (VTA) has been implicated in the control of sexual behavior, thus we further hypothesized that GHSR signaling in the VTA is important for social motivation. Thus, we conducted studies where we delivered JMV2959 to block GHSR in the VTA of mice, and studies where we rescued the expression of GHSR in the VTA of GHSR knockout (KO) mice. Mice lacking GHSR or injected with JMV2959 peripherally for 3 consecutive days displayed lower social motivation as reflected by a longer latency to approach a novel conspecific and shorter interaction time compared to WT or vehicle-treated controls. Furthermore, intra-VTA infusion of JMV2959 resulted in longer latencies to approach a novel conspecific, whereas GHSR KO mice with partial rescue of the GHSR showed decreased latencies to begin a novel social interaction. Together, these data suggest that GHSR in the VTA facilitate social approach in male mice, and GHSR-signaling deficits within the VTA result in reduced motivation to interact socially.
Drug-resistant cancer cell-derived exosomal EphA2 promotes breast cancer metastasis via the EphA2-Ephrin A1 reverse signaling
Authors: Gao Zicong , Han Xingxing , Zhu Yuying , Zhang He , Tian Ran , Wang Zhiyong , Cui Yanfen , Wang Zhaosong , Niu Ruifang , Zhang Fei
Published: April 2021

Tumor metastasis induced by drug resistance is a major challenge in successful cancer treatment. Nevertheless, the mechanisms underlying the pro-invasive and metastatic ability of drug resistance remain elusive. Exosome-mediated intercellular communications between cancer cells and stromal cells in tumor microenvironment are required for cancer initiation and progression. Recent reports have shown that communications between cancer cells also promote tumor aggression. However, little attention has been regarded on this aspect. Herein, we demonstrated that drug-resistant cell-derived exosomes promoted the invasion of sensitive breast cancer cells. Quantitative proteomic analysis showed that EphA2 was rich in exosomes from drug-resistant cells. Exosomal EphA2 conferred the invasive/metastatic phenotype transfer from drug-resistant cells to sensitive cells. Moreover, exosomal EphA2 activated ERK1/2 signaling through the ligand Ephrin A1-dependent reverse pathway rather than the forward pathway, thereby promoting breast cancer progression. Our findings indicate the key functional role of exosomal EphA2 in the transmission of aggressive phenotype between cancer cells that do not rely on direct cell–cell contact. Our study also suggests that the increase of EphA2 in drug-resistant cell-derived exosomes may be an important mechanism of chemotherapy/drug resistance-induced breast cancer progression.
DDRGK1, a crucial player of ufmylation system, is indispensable for autophagic degradation by regulating lysosomal function
Authors: Cao Yan , Li Rongyang , Shen Ming , Li Chengyu , Zou Yan , Jiang Qiang , Liu Shuo , Lu Chunwan , Li Honglin , Liu Honglin , Cai Yafei
Published: April 2021

DDRGK domain-containing protein 1 (DDRGK1) is an important component of the newly discovered ufmylation system and its absence has been reported to induce extensive endoplasmic reticulum (ER) stress. Recently, emerging evidence indicates that the ufmylation system is correlated with autophagy, although the exact mechanism remains largely unknown. To explore the regulation mechanism of DDRGK1 on autophagy, in this study, we established an immortalized mouse embryonic fibroblast (MEF) cell lines harvested from the DDRGK1F/F:ROSA26-CreERT2 mice, in which DDRGK1 depletion can be induced by 4-hydroxytamoxifen (4-OHT) treatment. Here, we show that DDRGK1 deficiency in MEFs has a dual effect on autophagy, which leads to a significant accumulation of autophagosomes. On one hand, it promotes autophagy induction by impairing mTOR signaling; on the other hand, it blocks autophagy degradation by inhibiting autophagosome–lysosome fusion. This dual effect of DDRGK1 depletion on autophagy ultimately aggravates apoptosis in MEFs. Further studies reveal that DDRGK1 loss is correlated with suppressed lysosomal function, including impaired Cathepsin D (CTSD) expression, aberrant lysosomal pH, and v-ATPase accumulation, which might be a potential trigger for impairment in autophagy process. Hence, this study confirms a crucial role of DDRGK1 as an autophagy regulator by controlling lysosomal function. It may provide a theoretical basis for the treatment strategies of various physiological diseases caused by DDRGK1 deficiency.
TAZ is required for chondrogenesis and skeletal development
Authors: Li Yang , Yang Shuting , Qin Ling , Yang Shuying
Published: April 2021

Chondrogenesis is a major contributor to skeletal development and maintenance, as well as bone repair. Transcriptional coactivator with PDZ-binding motif (TAZ) is a key regulator of osteogenesis and adipogenesis, but how TAZ regulates chondrogenesis and skeletal development remains undefined. Here, we found that TAZ expression is gradually increased during chondrogenic differentiation. Deletion of TAZ in chondrocyte lineage impaired articular and growth plate, as well as the bone development in TAZ-deficient mice. Consistently, loss of TAZ impaired fracture healing. Mechanistically, we found that ectopic expression of TAZ markedly promoted chondroprogenitor proliferation, while deletion of TAZ impaired chondrocyte proliferation and differentiation. TAZ associated with Sox5 to regulate the expression and stability of Sox5 and downstream chondrocyte marker genes’ expression. In addition, overexpression of TAZ enhanced Col10a1 expression and promoted chondrocyte maturation, which was blocked by deletion of TAZ. Overall, our findings demonstrated that TAZ is required for skeletal development and joint maintenance that provided new insights into therapeutic strategies for fracture healing, heterotopic ossification, osteoarthritis, and other bone diseases.
A central circadian oscillator confers defense heterosis in hybrids without growth vigor costs
Authors: Yang Li , Liu Pengtao , Wang Xuncheng , Jia Aolin , Ren Diqiu , Tang Yaru , Tang Yaqi , Deng Xing Wang , He Guangming
Published: April 2021

Plant immunity frequently incurs growth penalties, which known as the trade-off between immunity and growth. Heterosis, the phenotypic superiority of a hybrid over its parents, has been demonstrated for many traits but rarely for disease resistance. Here, we report that the central circadian oscillator, CCA1, confers heterosis for bacterial defense in hybrids without growth vigor costs, and it even significantly enhances the growth heterosis of hybrids under pathogen infection. The genetic perturbation of CCA1 abrogated heterosis for both defense and growth in hybrids. Upon pathogen attack, the expression of CCA1 in F1 hybrids is precisely modulated at different time points during the day by its rhythmic histone modifications. Before dawn of the first infection day, epigenetic activation of CCA1 promotes an elevation of salicylic acid accumulation in hybrids, enabling heterosis for defense. During the middle of every infection day, diurnal epigenetic repression of CCA1 leads to rhythmically increased chlorophyll synthesis and starch metabolism in hybrids, effectively eliminating the immunity-growth heterosis trade-offs in hybrids.
ARIH1 signaling promotes anti-tumor immunity by targeting PD-L1 for proteasomal degradation
Authors: Wu Youqian , Zhang Chao , Liu Xiaolan , He Zhengfu , Shan Bing , Zeng Qingxin , Zhao Qingwei , Zhu Huaying , Liao Hongwei , Cen Xufeng , Xu Xiaoyan , Zhang Mengmeng , Hou Tingjun , Wang Zhe , Yan Huanhuan , Yang Shuying , Sun Yaqin , Chen Yanying , Wu Ronghai , Xie Tingxue , Chen Wei , Najafov Ayaz , Ying Songmin , Xia Hongguang
Published: April 2021

Cancer expression of PD-L1 suppresses anti-tumor immunity. PD-L1 has emerged as a remarkable therapeutic target. However, the regulation of PD-L1 degradation is not understood. Here, we identify several compounds as inducers of PD-L1 degradation using a high-throughput drug screen. We find EGFR inhibitors promote PD-L1 ubiquitination and proteasomal degradation following GSK3α-mediated phosphorylation of Ser279/Ser283. We identify ARIH1 as the E3 ubiquitin ligase responsible for targeting PD-L1 to degradation. Overexpression of ARIH1 suppresses tumor growth and promotes cytotoxic T cell activation in wild-type, but not in immunocompromised mice, highlighting the role of ARIH1 in anti-tumor immunity. Moreover, combining EGFR inhibitor ES-072 with anti-CTLA4 immunotherapy results in an additive effect on both tumor growth and cytotoxic T cell activation. Our results delineate a mechanism of PD-L1 degradation and cancer escape from immunity via EGFR-GSK3α-ARIH1 signaling and suggest GSK3α and ARIH1 might be potential drug targets to boost anti-tumor immunity and enhance immunotherapies.
Chromatic micromaps in primary visual cortex
Authors: Chatterjee Soumya , Ohki Kenichi , Reid R. Clay
Published: April 2021

The clustering of neurons with similar response properties is a conspicuous feature of neocortex. In primary visual cortex (V1), maps of several properties like orientation preference are well described, but the functional architecture of color, central to visual perception in trichromatic primates, is not. Here we used two-photon calcium imaging in macaques to examine the fine structure of chromatic representation and found that neurons responsive to spatially uniform, chromatic stimuli form unambiguous clusters that coincide with blobs. Further, these responsive groups have marked substructure, segregating into smaller ensembles or micromaps with distinct chromatic signatures that appear columnar in upper layer 2/3. Spatially structured chromatic stimuli revealed maps built on the same micromap framework but with larger subdomains that go well beyond blobs. We conclude that V1 has an architecture for color representation that switches between blobs and a combined blob/interblob system based on the spatial content of the visual scene.
Suppression of pancreatic ductal adenocarcinoma growth and metastasis by fibrillar collagens produced selectively by tumor cells
Authors: Tian Chenxi , Huang Ying , Clauser Karl R. , Rickelt Steffen , Lau Allison N. , Carr Steven A. , Vander Heiden Matthew G. , Hynes Richard O.
Published: April 2021

Pancreatic ductal adenocarcinoma (PDAC) has a collagen-rich dense extracellular matrix (ECM) that promotes malignancy of cancer cells and presents a barrier for drug delivery. Data analysis of our published mass spectrometry (MS)-based studies on enriched ECM from samples of progressive PDAC stages reveal that the C-terminal prodomains of fibrillar collagens are partially uncleaved in PDAC ECM, suggesting reduced procollagen C-proteinase activity. We further show that the enzyme responsible for procollagen C-proteinase activity, bone morphogenetic protein1 (BMP1), selectively suppresses tumor growth and metastasis in cells expressing high levels of COL1A1. Although BMP1, as a secreted proteinase, promotes fibrillar collagen deposition from both cancer cells and stromal cells, only cancer-cell-derived procollagen cleavage and deposition suppresses tumor malignancy. These studies reveal a role for cancer-cell-derived fibrillar collagen in selectively restraining tumor growth and suggest stratification of patients based on their tumor epithelial collagen I expression when considering treatments related to perturbation of fibrillar collagens.
Optimized photochemistry enables efficient analysis of dynamic RNA structuromes and interactomes in genetic and infectious diseases
Authors: Zhang Minjie , Li Kongpan , Bai Jianhui , Velema Willem A. , Yu Chengqing , van Damme Ryan , Lee Wilson H. , Corpuz Maia L. , Chen Jian-Fu , Lu Zhipeng
Published: April 2021

Direct determination of RNA structures and interactions in living cells is critical for understanding their functions in normal physiology and disease states. Here, we present PARIS2, a dramatically improved method for RNA duplex determination in vivo with >4000-fold higher efficiency than previous methods. PARIS2 captures ribosome binding sites on mRNAs, reporting translation status on a transcriptome scale. Applying PARIS2 to the U8 snoRNA mutated in the neurological disorder LCC, we discover a network of dynamic RNA structures and interactions which are destabilized by patient mutations. We report the first whole genome structure of enterovirus D68, an RNA virus that causes polio-like symptoms, revealing highly dynamic conformations altered by antiviral drugs and different pathogenic strains. We also discover a replication-associated asymmetry on the (+) and (−) strands of the viral genome. This study establishes a powerful technology for efficient interrogation of the RNA structurome and interactome in human diseases.
Selectivity of mRNA degradation by autophagy in yeast
Authors: Makino Shiho , Kawamata Tomoko , Iwasaki Shintaro , Ohsumi Yoshinori
Published: April 2021

Synthesis and degradation of cellular constituents must be balanced to maintain cellular homeostasis, especially during adaptation to environmental stress. The role of autophagy in the degradation of proteins and organelles is well-characterized. However, autophagy-mediated RNA degradation in response to stress and the potential preference of specific RNAs to undergo autophagy-mediated degradation have not been examined. In this study, we demonstrate selective mRNA degradation by rapamycin-induced autophagy in yeast. Profiling of mRNAs from the vacuole reveals that subsets of mRNAs, such as those encoding amino acid biosynthesis and ribosomal proteins, are preferentially delivered to the vacuole by autophagy for degradation. We also reveal that autophagy-mediated mRNA degradation is tightly coupled with translation by ribosomes. Genome-wide ribosome profiling suggested a high correspondence between ribosome association and targeting to the vacuole. We propose that autophagy-mediated mRNA degradation is a unique and previously-unappreciated function of autophagy that affords post-transcriptional gene regulation.
Ultra-strong polymeric hollow fiber membranes for saline dewatering and desalination
Authors: Liang Can Zeng , Askari Mohammad , Choong Looh Tchuin , Chung Tai-Shung
Published: April 2021

Osmotically assisted reverse osmosis (OARO) has become an emerging membrane technology to tackle the limitations of a reverse osmosis (RO) process for water desalination. A strong membrane that can withstand a high hydraulic pressure is crucial for the OARO process. Here, we develop ultra-strong polymeric thin film composite (TFC) hollow fiber membranes with exceptionally high hydraulic burst pressures of up to 110 bar, while maintaining high pure water permeance of around 3 litre/(m2 h bar) and a NaCl rejection of about 98%. The ultra-strong TFC hollow fiber membranes are achieved mainly by tuning the concentration of the host polymer in spinning dopes and engineering the fiber dimension and morphology. The optimal TFC membranes display promising water permeance under the OR and OARO operation modes. This work may shed new light on the fabrication of ultra-strong TFC hollow fiber membranes for water treatments and desalination.
Author Correction: Discovering the genes mediating the interactions between chronic respiratory diseases in the human interactome
Authors: Maiorino Enrico , Baek Seung Han , Guo Feng , Zhou Xiaobo , Kothari Parul H. , Silverman Edwin K. , Barabási Albert-László , Weiss Scott T. , Raby Benjamin A. , Sharma Amitabh
Published: April 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-22939-x
Immunogenicity and efficacy of mRNA COVID-19 vaccine MRT5500 in preclinical animal models
Authors: Kalnin Kirill V. , Plitnik Timothy , Kishko Michael , Zhang Jinrong , Zhang Donghui , Beauvais Adrien , Anosova Natalie G. , Tibbitts Tim , DiNapoli Josh , Ulinski Gregory , Piepenhagen Peter , Cummings Sheila M. , Bangari Dinesh S. , Ryan Susan , Huang Po-Wei D. , Huleatt James , Vincent Deanne , Fries Katherine , Karve Shrirang , Goldman Rebecca , Gopani Hardip , Dias Anusha , Tran Khang , Zacharia Minnie , Gu Xiaobo , Boeglin Lianne , Abysalh Jonathan , Vargas Jorel , Beaulieu Angela , Shah Monic , Jeannotte Travis , Gillis Kimberly , Chivukula Sudha , Swearingen Ron , Landolfi Victoria , Fu Tong-Ming , DeRosa Frank , Casimiro Danilo
Published: April 2021

Emergency use authorization of COVID vaccines has brought hope to mitigate pandemic of coronavirus disease 2019 (COVID-19). However, there remains a need for additional effective vaccines to meet the global demand and address the potential new viral variants. mRNA technologies offer an expeditious path alternative to traditional vaccine approaches. Here we describe the efforts to utilize an mRNA platform for rational design and evaluations of mRNA vaccine candidates based on the spike (S) glycoprotein of SARS-CoV-2. Several mRNA constructs of S-protein, including wild type, a pre-fusion stabilized mutant (2P), a furin cleavage-site mutant (GSAS) and a double mutant form (2P/GSAS), as well as others, were tested in animal models for their capacity to elicit neutralizing antibodies (nAbs). The lead 2P/GSAS candidate was further assessed in dose-ranging studies in mice and Cynomolgus macaques, and for efficacy in a Syrian golden hamster model. The selected 2P/GSAS vaccine formulation, designated MRT5500, elicited potent nAbs as measured in neutralization assays in all three preclinical models and more importantly, protected against SARS-CoV-2-induced weight loss and lung pathology in hamsters. In addition, MRT5500 elicited TH1-biased responses in both mouse and non-human primate (NHP), thus alleviating a hypothetical concern of potential vaccine-associated enhanced respiratory diseases known associated with TH2-biased responses. These data position MRT5500 as a viable vaccine candidate for entering clinical development.
Overexpression of PVR and PD-L1 and its association with prognosis in surgically resected squamous cell lung carcinoma
Authors: Lee Jii Bum , Hong Min Hee , Park Seong Yong , Chae Sehyun , Hwang Daehee , Ha Sang-Jun , Shim Hyo Sup , Kim Hye Ryun
Published: April 2021

Targeting T-Cell Immunoreceptor with Ig and ITIM domain-poliovirus receptor (PVR) pathway is a potential therapeutic strategy in lung cancer. We analyzed the expression of PVR and programmed death ligand-1 (PD-L1) in surgically resected squamous cell lung carcinoma (SQCC) and determined its prognostic significance. We collected archival surgical specimens and data of 259 patients with SQCC at Yonsei Cancer Center (1998–2020). Analysis of variance was used to analyze the correlations between PVR and PD-L1 expression and patient characteristics. Kaplan–Meier curves were used to estimate recurrence-free survival (RFS) and overall survival (OS). Most patients were male (93%); the majority were diagnosed with stage 1 (47%), followed by stage 2 (29%) and stage 3 (21%). Overexpression of PVR resulted in a significantly shorter median RFS and OS (P = 0.01). PD-L1 expression was not significant in terms of prognosis. Patients were subdivided into four groups based on low and high PVR and PD-L1 expression. Those expressing high levels of PVR and PD-L1 had the shortest RFS (P = 0.03). PVR overexpression is associated with a poor prognosis in surgically resected SQCC. Inhibition of PVR as well as PD-L1 may help overcome the lack of response to immune checkpoint monotherapy.
Proteoglycans contribute to the functional integrity of the glomerular endothelial cell surface layer and are regulated in diabetic kidney disease
Authors: Khramova Alina , Boi Roberto , Fridén Vincent , Granqvist Anna Björnson , Nilsson Ulf , Tenstad Olav , Oveland Eystein , Haraldsson Börje , Ebefors Kerstin , Nyström Jenny
Published: April 2021

All capillary endothelia, including those of the glomeruli, have a luminal cell surface layer (ESL) consisting of glycoproteins, glycolipids, proteoglycans (PGs) and glycosaminoglycans. Previous results have demonstrated that an intact ESL is necessary for a normal filtration barrier and damage to the ESL coupled to proteinuria is seen for example in diabetic kidney disease (DKD). We used the principles of ion exchange chromatography in vivo to elute the highly negatively charged components of the ESL with a 1 M NaCl solution in rats. Ultrastructural morphology and renal function were analyzed and 17 PGs and hyaluronan were identified in the ESL. The high salt solution reduced the glomerular ESL thickness, led to albuminuria and reduced GFR. To assess the relevance of ESL in renal disease the expression of PGs in glomeruli from DKD patients in a next generation sequencing cohort was investigated. We found that seven of the homologues of the PGs identified in the ESL from rats were differently regulated in patients with DKD compared to healthy subjects. The results show that proteoglycans and glycosaminoglycans are essential components of the ESL, maintaining the permselective properties of the glomerular barrier and thus preventing proteinuria.
Probability of severe postpartum hemorrhage in repeat cesarean deliveries: a multicenter retrospective study in China
Authors: Du Lili , Feng Ling , Bi Shilei , Zhang Lizi , Tang Jingman , Zhong Liuying , Zhou Xingnan , Tan Hu , Huang Lijun , Lin Lin , Zeng Shanshan , Ren Luwen , Cao Yinli , Jia Jinping , Zhao Xianlan , Wang Shaoshuai , Xu Xiaoyan , Zhao Yangyu , Wang Zhijian , Zhu Qiying , Qi Hongbo , Zhang Lanzhen , Wen Suiwen , Li Hongtian , Chen Jingsi , Chen Dunjin
Published: April 2021

To determine the factors predicting the probability of severe postpartum hemorrhage (SPPH) in women undergoing repeat cesarean delivery (RCD). This multicenter, retrospective cohort study involved women who underwent RCD from January 2017 to December 2017, in 11 public tertiary hospitals within 7 provinces of China. The all-variables model and the multivariable logistic regression model (pre-operative, operative and simple model) were developed to estimate the probability of SPPH in development data and external validated in validation data. Discrimination and calibration were evaluated and clinical impact was determined by decision curve analysis. The study consisted of 11,074 women undergoing RCD. 278 (2.5%) women experienced SPPH. The pre-operative simple model including 9 pre-operative features, the operative simple model including 4 pre-operative and 2 intraoperative features and simple model including only 4 closely related pre-operative features showed AUC 0.888, 0.864 and 0.858 in development data and 0.921, 0.928 and 0.925 in validation data, respectively. Nomograms were developed based on predictive models for SPPH. Predictive tools based on clinical characteristics can be used to estimate the probability of SPPH in patients undergoing RCD and help to allow better preparation and management of these patients by using a multidisciplinary approach of cesarean delivery for obstetrician.
Characterization of an anterior segment organ culture model for open globe injuries
Authors: Snider Eric J. , Boice Emily N. , Gross Brandon , Butler Jacinque J. , Zamora David O.
Published: April 2021

Open-globe injuries have poor visual outcomes and have increased in frequency. The current standard of care is inadequate, and a therapeutic is needed to stabilize the injury until an ophthalmic specialist is reached. Unfortunately, current models or test platforms for open-globe injuries are insufficient. Here, we develop and characterize an open-globe injury model using an anterior segment organ-culture platform that allows therapeutic assessment for up to 72 h post-injury. Anterior segments maintained in organ culture were kept at physiological intraocular pressure throughout, and puncture injuries were created using a novel pneumatic-powered system. This system can create high-speed, military-relevant injuries up to 4.5 mm in diameter through the cornea. From intraocular pressure readings, we confirmed a loss of pressure across the 72 h after open-globe injury. Proof-of-concept studies with a Dermabond tissue adhesive were performed to show how this model system could track therapeutic performance for 72 h. Overall, the organ-culture platform was found to be a suitable next step towards modeling open-globe injuries and assessing wound closure over the critical 72 h post-injury. With improved models such as this, novel biomaterial therapeutics development can be accelerated, improving care, and, thus, improving the prognosis for the patients.
The sublethal effects of neonicotinoids on spiders are independent of their nutritional status
Authors: Řezáč Milan , Gloríková Nela , Wilder Shawn M. , Heneberg Petr
Published: April 2021

Spiders were recently shown to be adversely affected by field-realistic concentrations of a broad scale of neonicotinoid insecticides. Among the reported effects of neonicotinoids on invertebrates were declines in lipid biosynthesis and upregulation of β-oxidation, while vertebrate models suggest increased adipogenesis following treatment with neonicotinoids. Therefore, we hypothesized that there exists synergy between the effects of diet and concurrent exposure to field-realistic concentrations of neonicotinoid insecticides. To address this hypothesis, we fed first instars of the large wolf spiderHogna antelucanawith two types of diets and exposed them to field-realistic concentrations of three formulations of neonicotinoids (thiamethoxam, thiacloprid and acetamiprid). We then measured the growth of the tested spiders; the lipid and protein content of their bodies; and their behavior, including ballooning, rappelling, and locomotor parameters. The two tested diets consisted of casein-treated and sucrose-treatedDrosophila melanogaster. The dietary treatments affected the lipid and protein content of the spiders, their body weight and carapace length but did not affect any of the measured behavioral parameters. Surprisingly, we did not find any effects of acute exposure to neonicotinoid insecticides on the lipid or protein reserves of spiders. Exposure to neonicotinoids altered the behavior of the spiders as reported previously in other spider species; however, these effects were not affected by dietary treatments. Overall, the dietary treatments did not have any major synergy with acute exposure to field-realistic concentrations of neonicotinoid insecticides.
Individuals with controlled hypertension show endothelial integrity following a bout of moderate-intensity exercise: randomized clinical trial
Authors: Waclawovsky Gustavo , Boll Liliana F. C. , Eibel Bruna , Alegretti Ana Paula , Spagnol Fabiane , De Paoli Juliana , Wajner Simone , Marschner Rafael A. , Schaun Maximiliano I. , Lehnen Alexandre Machado
Published: April 2021

To examine the acute effects of aerobic exercise (AE), resistance exercise (RE) or combined exercise (CE) on flow-mediated dilation (FMD), progenitor cells (PCs), endothelial progenitor cells (EPCs), oxidative stress markers and endothelial-cell derived microvesicles (EMVs) in patients with hypertension. This is a randomized, parallel-group clinical trial involving an intervention of one session of three different modalities of exercise. Thirty-three males (43 ± 2y) were randomly divided into three groups: a session of AE (n = 11, 40 min, cycle ergometer, 60% HRR); a session of RE (n = 11, 40 min, 4 × 12 lower limb repetitions, 60% 1-RM); or a session of CE (n = 11, 20-min RE + 20-min AE). FMD was assessed 10 min before and 10, 40 and 70 min post-intervention. Blood samples were collected at the same time points (except 40 min). FMD were similar in all groups and from baseline (within each group) after a single exercise bout (AE, RE or CE). At 70 min, RE group showed higher levels of PCs compared to the AE (81%) and CE group (60%). PC levels were reduced from baseline in all groups (AE: 32%, p = 0.037; RE: 15%, p = 0.003; CE: 17%, p = 0.048). The levels of EPCs, EMVs and oxidative stress were unchanged. There were no acute effects of moderate-intensity exercise on FMD, EPCs, EMVs and oxidative stress, but PCs decreased regardless of the exercise modality. Individuals with controlled hypertension do not seem to have impaired vascular function in response to a single exercise bout.
Integrating online and offline data for crisis management: Online geolocalized emotion, policy response, and local mobility during the COVID crisis
Authors: Feng Shihui , Kirkley Alec
Published: April 2021

Integrating online and offline data is critical for uncovering the interdependence between policy and public emotional and behavioral responses in order to aid the development of effective spatially targeted interventions during crises. As the COVID-19 pandemic began to sweep across the US it elicited a wide spectrum of responses, both online and offline, across the population. Here, we analyze around 13 million geotagged tweets in 49 cities across the US from the first few months of the pandemic to assess regional dependence in online sentiments with respect to a few major COVID-19 related topics, and how these sentiments correlate with policy development and human mobility. In this study, we observe universal trends in overall and topic-based sentiments across cities over the time period studied. We also find that this online geolocalized emotion is significantly impacted by key COVID-19 policy events. However, there is significant variation in the emotional responses to these policies across the cities studied. Online emotional responses are also found to be a good indicator for predicting offline local mobility, while the correlations between these emotional responses and local cases and deaths are relatively weak. Our findings point to a feedback loop between policy development, public emotional responses, and local mobility, as well as provide new insights for integrating online and offline data for crisis management.
Predicting language recovery in post-stroke aphasia using behavior and functional MRI
Authors: Iorga Michael , Higgins James , Caplan David , Zinbarg Richard , Kiran Swathi , Thompson Cynthia K. , Rapp Brenda , Parrish Todd B.
Published: April 2021

Language outcomes after speech and language therapy in post-stroke aphasia are challenging to predict. This study examines behavioral language measures and resting state fMRI (rsfMRI) as predictors of treatment outcome. Fifty-seven patients with chronic aphasia were recruited and treated for one of three aphasia impairments: anomia, agrammatism, or dysgraphia. Treatment effect was measured by performance on a treatment-specific language measure, assessed before and after three months of language therapy. Each patient also underwent an additional 27 language assessments and a rsfMRI scan at baseline. Patient scans were decomposed into 20 components by group independent component analysis, and the fractional amplitude of low-frequency fluctuations (fALFF) was calculated for each component time series. Post-treatment performance was modelled with elastic net regression, using pre-treatment performance and either behavioral language measures or fALFF imaging predictors. Analysis showed strong performance for behavioral measures in anomia (R2 = 0.948, n = 28) and for fALFF predictors in agrammatism (R2 = 0.876, n = 11) and dysgraphia (R2 = 0.822, n = 18). Models of language outcomes after treatment trained using rsfMRI features may outperform models trained using behavioral language measures in some patient populations. This suggests that rsfMRI may have prognostic value for aphasia therapy outcomes.
Delay in primordial germ cell migration in adamts9 knockout zebrafish
Authors: Carver Jonathan J. , He Yuanfa , Zhu Yong
Published: April 2021

Adamts9 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 9) is one of a few metalloproteinases structurally conserved from C. elegans to humans and is indispensable in germ cell migration in invertebrates. However, adamts9′s roles in germ cell migration in vertebrates has not been examined. In the present study, we found zygotic expression of adamts9 started around the germ ring stage and reached peak levels at 3 days post fertilization (dpf) in zebrafish. The migration of primordial germ cells (PGC) was completed within 24 hours (h) in wildtype siblings, while a delay in PGC migration was found at 15 and 24-h post-fertilization (hpf) in the Adamts9 knockout (KO). However, the delayed PGC migration in Adamts9 KO disappeared at 48 hpf. Our study suggests a conserved function of Adamts9 in germ cell migration among invertebrates and vertebrates. In addition, our results also suggest that Adamts9 is not essential for germ cell migration as reported in C. elegans, possibly due to expansion of Adamts family members and compensatory roles from other metalloproteinases in vertebrates. Further studies are required in order to elucidate the functions and mechanisms of metalloproteinases in germ cell migration and gonad formation in vertebrates.
Transcriptomic analysis to infer key molecular players involved during host response to NDV challenge in Gallus gallus (Leghorn & Fayoumi)
Authors: Vanamamalai Venkata Krishna , Garg Priyanka , Kolluri Gautham , Gandham Ravi Kumar , Jali Itishree , Sharma Shailesh
Published: April 2021

Long non-coding RNAs (lncRNAs) are the transcripts of length longer than 200 nucleotides. They are involved in the regulation of various biological activities. Leghorn and Fayoumi breeds of Gallus gallus were known to be having differential resistance against Newcastle Disease Virus (NDV) infection. Differentially expressed genes which were thought to be involved in this pattern of resistance were already studied. Here we report the analysis of the transcriptomic data of Harderian gland of Gallus gallus for studying the lncRNAs involved in regulation of these genes. Using bioinformatics approaches, a total of 37,411 lncRNAs were extracted and 359 lncRNAs were differentially expressing. Functional annotation using co-expression analysis revealed the involvement of lncRNAs in the regulation of various pathways. We also identified 1232 quantitative trait loci (QTLs) associated with the genes interacting with lncRNA. Additionally, we identified the role of lncRNAs as putative micro RNA precursors, and the interaction of differentially expressed Genes with transcription factors and micro RNAs. Our study revealed the role of lncRNAs during host response against NDV infection which would facilitate future experiments in unravelling regulatory mechanisms of development in the genetic improvement of the susceptible breeds of Gallus gallus.
Physical activity, screen exposure and sleep among students during the pandemic of COVID-19
Authors: Guo Yang-feng , Liao Min-qi , Cai Wei-li , Yu Xiao-xuan , Li Shu-na , Ke Xing-yao , Tan Si-xian , Luo Ze-yan , Cui Yun-feng , Wang Qian , Gao Xu-ping , Liu Jun , Liu Yan-hua , Zhu Sui , Zeng Fang-fang
Published: April 2021

This study aimed to determine the levels of health-related behaviours (physical activity, screen exposure and sleep status) among Chinese students from primary, secondary and high schools during the pandemic of COVID-19, as well as their changes compared with their status before the pandemic. A cross-sectional online survey of 10,933 students was conducted among 10 schools in Guangzhou, China, between 8th and 15th March, 2020. After getting the informed consent from student’s caregivers, an online questionnaire was designed and used to obtain time spending on health-related behaviours during the pandemic of COVID-19, as well as the changes compared with 3 months before the pandemic, which was completed by students themselves or their caregivers. Students were stratified by regions (urban, suburban, exurban), gender (boys and girls), and grades (lower grades of primary school, higher grades of primary schools, secondary schools and high schools). Data were expressed as number and percentages and Chi-square test was used to analyse difference between groups. Overall, the response rate of questionnaire was 95.3% (10,416/10,933). The median age of included students was 13.0 (10.0, 16.0) years and 50.1% (n = 5,219) were boys. 41.4%, 53.6% and 53.7% of total students reported less than 15 min per day in light, moderate and vigorous activities and 58.7% (n = 6,113) reported decreased participation in physical activity compared with the time before pandemic. Over 5 h of screen time spending on online study was reported by 44.6% (n = 4,649) of respondents, particular among high school students (81.0%). 76.9% of students reported increased screen time compared with the time before pandemic. Inadequate sleep was identified among 38.5% of students and the proportion was highest in high school students (56.9%). Our study indicated that, during the COVID-19 pandemic, the school closure exerted tremendous negative effects on school-aged children’s health habits, including less physical activity, longer screen exposure and irregular sleeping pattern.
Pulsed 3.5 GHz high power microwaves irradiation on physiological solution and their biological evaluation on human cell lines
Authors: Bhartiya Pradeep , Mumtaz Sohail , Lim Jun Sup , Kaushik Neha , Lamichhane Pradeep , Nguyen Linh Nhat , Jang Jung Hyun , Yoon Sang Ho , Choi Jin Joo , Kaushik Nagendra Kumar , Choi Eun Ha
Published: April 2021

Microwave (MW) radiation is increasingly being used for several biological applications. Many investigations have focused on understanding the potential influences of pulsed MW irradiation on biological solutions. The current study aimed to investigate the effects of 3.5 GHz pulsed MW radiation-irradiated liquid solutions on the survival of human cancer and normal cells. Different physiological solutions such as phosphate buffer saline, deionized water, and Dulbecco’s modified Eagle medium (DMEM) for cell culture growth were irradiated with pulsed MW radiation (45 shots with the energy of 1 mJ/shot). We then evaluated physiological effects such as cell viability, metabolic activity, mitochondrial membrane potential, cell cycle, and cell death in cells treated with MW-irradiated biological solutions. As MW irradiation with power density ~ 12 kW/cm2 mainly induces reactive nitrogen oxygen species in deionized water, it altered the cell cycle, membrane potential, and cell death rates in U373MG cells due to its high electric field ~ 11 kV/cm in water. Interestingly, MW-irradiated cell culture medium and phosphate-buffered saline did not alter the cellular viability and metabolic energy of cancer and normal cells without affecting the expression of genes responsible for cell death. Taken together, MW-irradiated water can alter cellular physiology noticeably, whereas irradiated media and buffered saline solutions induce negligible or irrelevant changes that do not affect cellular health.
Author Correction: Automation of surgical skill assessment using a three-stage machine learning algorithm
Authors: Lavanchy Joël L. , Zindel Joel , Kirtac Kadir , Twick Isabell , Hosgor Enes , Candinas Daniel , Beldi Guido
Published: April 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Deficit saline water irrigation under reduced tillage and residue mulch improves soil health in sorghum-wheat cropping system in semi-arid region
Authors: Soni Pooja Gupta , Basak Nirmalendu , Rai Arvind Kumar , Sundha Parul , Narjary Bhaskar , Kumar Parveen , Yadav Gajender , Kumar Satyendra , Yadav Rajender Kumar
Published: April 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Iron oxide xerogels for improved water quality monitoring of arsenic(iii) in resource-limited environmentsviasolid-phase extraction, preservation, storage, transportation, and analysis of trace contaminants (SEPSTAT)
Authors: Bono Michael S. , Hanhauser Emily B. , Vaishnav Chintan , Hart A. John , Karnik Rohit
Published: April 2021

We show that iron oxide xerogels can quantitatively adsorb, store, and release aqueous arsenic(iii), enabling a new arsenic monitoring paradigm where sample contamination is adsorbed onto solid sorbents for transportation to laboratories for analysis.
Metal-enhanced sensing platform for the highly sensitive detection of C-reactive protein antibody and rhodamine B with applications in cardiovascular diseases and food safety
Authors: Thao Nguyen Thanh , Hoang Thi Xoan , Phan Thang Bach , Kim Jae Young , Ta Hanh Kieu Thi , Trinh Kieu The Loan , Tran Nhu Hoa Thi
Published: April 2021

The potential applications of metal-enhanced fluorescence (MEF) devices include biosensors for the detection of trace amounts in biosciences, biotechnology, and pathogens that are relevant to medical diagnostics and food control.
Cadmium doping for improving the efficiency and stability of carbon-based CsPbIBr2 all-inorganic perovskite solar cells
Authors: Wang Rufeng , Zhang Haiming , Han Siqi , Wu Yizhi , Hu Zhanning , Zhang Guixiang , Liu Haoxuan , He Qingchen , Zhang Xianjing
Published: April 2021

Cadmium ions are doped into perovskite lattice for enhancing the efficiency and stability of carbon-based CsPbIBr2 all-inorganic perovskite solar cells.
Highly sensitive and selective colorimetric detection of dual metal ions (Hg2+and Sn2+) in water: an eco-friendly approach
Authors: Paw Rintumoni , Hazarika Moushumi , Boruah Purna K. , Kalita Amlan Jyoti , Guha Ankur K. , Das Manash R. , Tamuly Chandan
Published: April 2021

Synthesis of Ag nanoparticles using Allin based garlic extract for highly sensitive and selective detection of metal ions Hg2+and Sn2+in water. The limit of detection (LoD) for Hg2+and Sn2+ions were found as 15.7 nM and 11.25 nM respectively.
Reaping the catalytic benefits of both surface (NiFe2O4) and underneath (Ni3Fe) layers for the oxygen evolution reaction
Authors: Alharthy Mohammad , Suliman Munzir H. , Al-Betar Abdul-Rahman , Wang Yuan , Tian Ziqi , Drmosh Qasem A. , Yamani Zain H. , Qamar Mohammad
Published: April 2021

Facile growth of a crystalline monolayer of NiFe2O4 encompassing Ni3Fe embedded within a polyaniline matrix for the oxygen evolution reaction.
A label-free fluorescent biosensor based on a catalyzed hairpin assembly for HIV DNA and lead detection
Authors: Xiong Yu , Dai Jianyuan , Zhang Yujiao , Zhou Cuisong , Yuan Hongyan , Xiao Dan
Published: April 2021

Herein, a label-free fluorescent signal amplification system based on a catalyzed hairpin assembly (CHA) is reported.
Thorium amidates function as single-source molecular precursors for thorium dioxide
Authors: Straub Mark D. , Ouellette Erik T. , Boreen Michael A. , Branson Jacob A. , Ditter Alex , Kilcoyne A. L. David , Lohrey Trevor D. , Marcus Matthew A. , Paley Maria , Ramirez José , Shuh David K. , Minasian Stefan G. , Arnold John
Published: April 2021

Volatile thorium amidates can be converted to ThO2 in the absence of an external oxygen source, and the thermal properties of these precursors can be readily tuned by modifying the ligand substituents.