bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of functional dyspepsia in medical students: protocol for a systematic review and meta-analysis
Authors: Caldas Giulior A. Marrull , Farfán Nicolas Silva , Sauca Andres Penny , Ortega Steffi N. Roca , Zafra-Tanaka Jessica Hanae 
Published: December 2020

AbstractBackgroundDyspepsia is defined as a syndrome that comprises a series of chronic and recurrent disorders in the upper digestive tract. According to a meta-analysis carried out in 2014, the worldwide prevalence of dyspepsia is 20.8%, being the highest prevalence found in South America with 37.7%. It was found that there are populations that present a higher prevalence of dyspepsia that is associated with high levels of stress, such as those that can be found in medical students, so It would be important to evaluate the population of medical students, since the medical career, by its nature, represents a great academic load on the student who may later suffer from gastrointestinal diseases.Review questionWhat is the prevalence of functional dyspepsia in medical students?ObjectiveTo determine the prevalence of dyspepsia in medical students and to assess genre differencesMethodsWe will conduct a systematic review and meta-analysis. We will use the following search engines: PubMed, Global Index Medicus and EMBASE using search terms related to functional dyspepsia and medical students. We will include observational studies (either cross-sectional or cohort studies) that assessed the prevalence of functional dyspepsia among this particular population.ConclusionCurrently, no systematic review or meta-analysis has been conducted about the prevalence of functional dyspepsia among this population of students. The aim of this work is to summarize the available literature regarding this topic.
Risk Factors for SARS-CoV-2 Seropositivity in a Health Care Worker Population
Authors: Schubl Sebastian D. , Figueroa Cesar , Palma Anton M. , de Assis Rafael R. , Jain Aarti , Nakajima Rie , Jasinkas Alguimantas , Brabender Danielle , Naaseh Ariana , Dominguez Oscar Hernandez , Runge Ava , Skochko Shannon , Chinn Justine , Kelsey Adam James , Lai Kieu Thai , Zhao Weian , Horvath Peter , Tifrea Delia , Grigorian Areg , Gonzales Abran , Adelsohn Suzanne , Zaldivar Frank , Edwards Robert , Amin Alpesh N. , Stamos Michael J. , Barie Philip S. , Felgner Philip L. , Khan Saahir 
Published: December 2020

AbstractBackgroundProtecting health care workers (HCWs) during the coronavirus disease 2019 (COVID-19) pandemic is essential. Serologic testing can identify HCWs who had minimally symptomatic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections that were missed by occupational screening based on daily symptom and temperature checks. Recent studies report conflicting results regarding the impact of occupational factors on SARS-CoV-2 seropositivity amongst HCWs.MethodsThe study population included all hospital workers at an academic medical center in Orange County, California. SARS-CoV-2 seropositivity was assessed from a fingerstick blood specimen using a coronavirus antigen microarray, which compares IgM and IgG antibodies against a panel of SARS-CoV-2 antigens with positive and negative controls to identify prior SARS-CoV-2 infection with 98% specificity and 93% sensitivity. Demographic, occupational, and clinical factors were surveyed and their effect on seropositivity estimated using multivariable logistic regression analysis.ResultsAmongst 1,557 HCWs with complete data, SARS-CoV-2 seropositivity was 10.8%. Risk factors for increased seropositivity included male gender, exposure to COVID-19 outside of work, working in food or environmental services, and working in COVID-19 units. Amongst the 1,103 HCW who were seropositive but missed by occupational screening, additional risk factors included younger age and working in administration.ConclusionsSARS-CoV-2 seropositivity is significantly higher than reported case counts even amongst HCWs who are meticulously screened. Seropositive HCWs missed by occupational screening were more likely to be younger, work roles without direct patient care, or have COVID-19 exposure outside of work.Key PointsSARS-CoV-2 seropositivity risk factors amongst health care workers included male gender, nonoccupational exposure, food or environmental services role, and COVID-19 unit location. Those missed by occupational screening were younger, in roles without direct patient care, or exposed outside of work.
TUGDA: Task uncertainty guided domain adaptation for robust generalization of cancer drug response prediction fromin vitrotoin vivosettings
Authors: da Silva Rafael Peres , Suphavilai Chayaporn , Nagarajan Niranjan 
Published: December 2020

AbstractOver the last decade, large-scale cancer omics studies have highlighted the diversity of patient molecular profiles and the importance of leveraging this information to deliver the right drug to the right patient at the right time. Key challenges in learning predictive models for this include the high-dimensionality of omics data, limitations in the number of data points available, and heterogeneity in biological and clinical factors affecting patient response. The use of multi-task learning (MTL) techniques has been widely explored to address dataset limitations forin vitrodrug response models, while domain adaptation (DA) has been employed to extend them to predict in vivo response. In both of these transfer learning settings, noisy data for some tasks (or domains) can substantially reduce the performance for others compared to single-task (domain) learners, i.e. lead to negative transfer (NT). We describe a novel multi-task unsupervised domain adaptation method (TUGDA) that addresses these limitations in a unified framework by quantifying uncertainty in predictors and weighting their influence on shared domain/task feature representations. TUGDA’s ability to rely more on predictors with low-uncertainty allowed it to notably reduce cases of negative transfer forin vitromodels (63% for drugs with limited data and 94% overall) compared to state-of-the-art methods. For domain adaptation toin vivosettings, TUGDA improved performance for 6 out of 12 drugs in patient-derived xenografts, and 7 out of 22 drugs in TCGA patient datasets, despite being trained in an unsupervised fashion. TUGDA’s ability to avoid negative transfer thus provides a key capability as we try to integrate diverse drug-response datasets to build consistent predictive models within vivoutility.Availabilityhttps://github.com/CSB5/TUGDA
The jasmine (Jasminum sambac) genome and flower fragrances
Authors: Chen Gang , Mostafa Salma , Lu Zhaogeng , Du Ran , Cui Jiawen , Wang Yun , Liao Qinggang , Lu Jinkai , Mao Xinyu , Chang Bang , Wang Li , Jia Zhichao , Yang Xiulian , Zhu Yingfang , Yan Jianbin , Jin Biao 
Published: December 2020

AbstractJasminum sambac, a world-renowned plant appreciated for its exceptional flower fragrance, is of cultural and economic importance. However, the genetic basis of its fragrance is largely unknown. Here, we present the firstde novogenome ofJ. sambacwith 550.12 Mb (scaffold N50 = 40.1 Mb) assembled into 13 pseudochromosomes. Terpene synthase genes associated with flower fragrance are significantly amplified in the form of gene clusters through tandem duplications in the genome. Eleven homolog genes within the SABATH super-family were identified as related to phenylpropanoid/benzenoid compounds. Several key genes regulating jasmonate biosynthesis were duplicated causing increased copy numbers. Furthermore, multi-omics analyses identified various aromatic compounds and the key genes involved in fragrance biosynthesis pathways. Our genome ofJ. sambacoffers a basic genetic resource for studying floral scent biosynthesis and provides an essential foundation for functional genomic research and variety improvements inJasminum.
Atg4 family proteins drive phagophore growth independently of the LC3/GABARAP lipidation system
Authors: Nguyen Thanh Ngoc , Padman Benjamin Scott , Zellner Susanne , Uoselis Louise , Skulsuppaisarn Marvin , Behrends Christian , Lazarou Michael 
Published: December 2020

SummaryThe sequestration of damaged mitochondria within double-membrane structures termed autophagosomes is a key step of PINK1/Parkin mitophagy. The Atg4 family of proteases are thought to regulate autophagosome formation exclusively by processing the ubiquitin-like Atg8 family (LC3/GABARAPs). We make the unexpected discovery that human Atg4s can directly promote autophagosome formation independently of their protease activity and of Atg8 family processing. High resolution structures of phagophores generated with artificial intelligence-directed 3D electron microscopy reveal a role for the Atg4 family in promoting phagophore-ER contacts during the lipid-transfer phase of autophagosome formation. Atg4 proximity interaction networks stimulated by PINK1/Parkin mitophagy are consistent with roles for Atg4s in protein/vesicle transport and lipid modification. We also show that Atg8 removal during autophagosome maturation does not depend on Atg4 de-lipidation activity as previously thought. Instead, we find that Atg4s can disassemble Atg8-protein conjugates, revealing a role for Atg4s as deubiquitinating-like enzymes. These findings establish non-canonical roles of the Atg4 family beyond the Atg8 lipidation axis and provide an AI driven framework for high-throughput 3D electron microscopy.
Conformational plasticity and dynamic interactions of the N-terminal domain of the chemokine receptor CXCR1
Authors: Kharche Shalmali , Joshi Manali , Chattopadhyay Amitabha , Sengupta Durba 
Published: December 2020

AbstractDynamic interactions between G protein-coupled receptors (GPCRs) and their cognate protein partners at the membrane interface control several cellular signaling pathways. An important example is the association of CXC chemokine receptor 1 (CXCR1) with its cognate chemokine, interleukin-8 (IL8 or CXCL8) that regulates neutrophil-mediated immune responses. Although the N-terminal domain of the receptor is known to confer ligand selectivity, the conformational dynamics of this intrinsically disordered region of CXCR1 in particular, and chemokine receptors in general, remains unresolved. In this work, we have explored the interaction of CXCR1 with IL8 by microsecond time scale coarse-grain simulations that were validated by atomistic models and NMR chemical shift predictions. We show that the conformational plasticity of theapo-receptorN-terminal region is restricted upon ligand binding, driving it to an open C-shaped conformation. Importantly, we validated the dynamic complex sampled in our simulations against chemical shift perturbations reported by previous NMR studies. Our results indicate that caution should be exercised when chemical shift perturbation is used as a reporter of residue contacts in such dynamic associations. We believe our results represent a step forward in devising a strategy to understand intrinsically disordered regions in GPCRs and how they acquire functionally important conformational ensembles in dynamic protein-protein interfaces.Author summaryHow cells communicate with the outside environment is intricately controlled and regulated by a large family of receptors on the cell membrane (G protein-coupled receptors or GPCRs) that respond to external signals (termed ligands). Chemokine receptors belong to this GPCR family and regulate immune responses. We analyze here the first step of binding of a representative chemokine receptor (CXCR1) with its natural ligand, interleukin 8 (IL8) by an extensive set of molecular dynamics simulations. Our work complements previous mutational and NMR experiments which lack molecular-level resolution. We show that in the inactive state, one of the extracellular domains of the CXCR1 receptor, namely the N-terminal domain, is highly flexible and like a “shape-shifter” can exist in multiple conformational states. However, when IL8 binds, the N-terminal domain undergoes a conformational freezing, and acquires a C-shaped “claw-like” structure. The complex between the receptor and IL8 is still quite dynamic as this C-shaped N-terminal domain forms an extensive but slippery interface with the ligand. We further validated these results by quantitative comparison with NMR and mutagenesis studies. Our work helps clarify the inherent disorder in N-terminal domains of chemokine receptors and demonstrates how this domain can acquire functionally important conformational states in dynamic protein-protein interfaces.
Chromosome-scale genome assembly of Japanese pear (Pyrus pyrifolia) variety ‘Nijisseiki’
Authors: Shirasawa Kenta , Itai Akihiro , Isobe Sachiko 
Published: December 2020

AbstractAimThe Japanese pear (P. pyrifolia) variety ‘Nijisseiki’ is valued for its superior flesh texture, which has led to its use as a breeding parent for most Japanese pear cultivars. However, in the absence of genomic resources for Japanese pear, the parents of the ‘Nijisseiki’ cultivar remain unknown, as does the genetic basis of its favorable texture. The genomes of pear and related species are complex due to ancestral whole genome duplication and high heterozygosity, and long-sequencing technology was used to address this.Methods and ResultsDe novo assembly of long sequence reads covered 136× of the Japanese pear genome and generated 503.9 Mb contigs consisting of 114 sequences with an N50 value of 7.6□Mb. Contigs were assigned to Japanese pear genetic maps to establish 17 chromosome-scale sequences. In total, 44,876 protein-encoding genes were predicted, 84.3% of which were supported by predicted genes and transcriptome data from Japanese pear relatives. As expected, evidence of whole genome duplication was observed, consistent with related species.Conclusion and PerspectiveThis is the first genome sequence analysis reported for Japanese pear, and this resource will support breeding programs and provide new insights into the physiology and evolutionary history of Japanese pear.
Do initial concentration and activated sludge seasonality affect pharmaceutical biodegradation rate constants?
Authors: van Bergen Tamara J.H.M. , Rios-Miguel Ana B. , Nolte Tom M. , Ragas Ad M.J. , van Zelm Rosalie , Graumans Martien , Scheepers Paul , Jetten Mike S.M. , Hendriks A. Jan , Welte Cornelia U. 
Published: December 2020

AbstractPharmaceuticals find their way to the aquatic environment via wastewater treatment plants (WWTPs) and biodegradation plays an important role in mitigating environmental risks, however a mechanistic understanding of involved processes is limited. The aim of this study was to evaluate potential relationships between first-order biodegradation rate constants (kb) of nine pharmaceuticals and initial concentration of the selected compounds, and sampling season of the used activated sludge inocula. Four-day bottle experiments were performed with activated sludge from WWTP Groesbeek (The Netherlands) of two different seasons, summer and winter, spiked with two environmentally relevant concentrations (3 and 30 nM) of pharmaceuticals. Concentrations of the compounds were measured by LC-MS/MS, microbial community composition was assessed by 16S rRNA gene amplicon sequencing and kbvalues were calculated. The biodegradable pharmaceuticals, ranked from high to low biodegradation rates, were acetaminophen, metformin, metoprolol, terbutaline, and phenazone. Carbamazepine, diatrizoic acid, diclofenac and fluoxetine were not converted. Summer and winter inocula did not show significant differences in microbial community composition, but resulted in a slightly different kbfor some pharmaceuticals. Likely microbial activity was responsible instead of community composition. In the same inoculum different kbvalues were measured, depending on initial concentration. In general, biodegradable compounds had a higher kbwhen the initial concentration was higher. This demonstrates that Michealis-Menten kinetics theory has shortcomings for some pharmaceuticals at low, environmentally relevant concentrations and that the pharmaceutical concentration should be taken into account when measuring the kbin order to reliably predict the fate of pharmaceuticals in the WWTP.
Clustered Loss of Dendritic Spines Characterizes Encoding of Related Memory
Authors: Kumar Suraj , Kumar Meenakshi Prabod , Kaushik Yagika , Jayaprakash Balaji 
Published: December 2020

AbstractGeneration of new spines is often thought of as a correlate of memory and loss of spines is considered representing memory loss. Contrary to common belief, we observe that spine loss has functional value in distinctly encoding related life events rather than causing memory loss. Using spatial autocorrelation of dendritic morphology obtained from in vivo longitudinal imaging, we show that clustered loss, rather than gain, of new spines characterizes the formation of related memory. This spatially selective dendritic spine loss occurs closer to new spines formed during the acquisition of initial memory. Thus, enabling the dendrites to store multiple memories and their inter relationship. Remarkably, we find acquisition of related memory in the absence of NMDAR activation increases the fraction of such correlated spine loss.
Cerebral μ-opioid and CB1-receptor systems have distinct roles in human feeding behavior
Authors: Kantonen Tatu , Karjalainen Tomi , Pekkarinen Laura , Isojärvi Janne , Kalliokoski Kari , Kaasinen Valtteri , Hirvonen Jussi , Nuutila Pirjo , Nummenmaa Lauri 
Published: December 2020

AbstractEating behavior varies greatly between healthy individuals, but the neurobiological basis of these trait-like differences in feeding remains unknown. Central µ-opioid receptors (MOR) and cannabinoid CB1-receptors (CB1R) regulate energy balance via multiple neural pathways, promoting food intake and reward. Because obesity and eating disorders have been associated with alterations in the brain’s opioid and endocannabinoid signaling, the variation in MOR and CB1R system function could potentially underlie distinct eating behavior phenotypes. In this retrospective positron emission tomography (PET) study, we analyzed [11C]carfentanil PET scans of MORs from 92 healthy subjects (70 males and 22 females), and [18F]FMPEP-d2scans of CB1Rs from 35 subjects (all males, all also included in the [11C]carfentanil sample). Eating styles were measured with the Dutch Eating Behavior Questionnaire (DEBQ). We found that lower cerebral MOR availability was associated with increased external eating – individuals with low MORs reported being more likely to eat in response to environment’s palatable food cues. CB1R availability was associated with multiple eating behavior traits. We conclude that although MORs and CB1Rs overlap anatomically and functionally in the brain, they have distinct roles in mediating individual feeding patterns.
Using physiological signals to predict temporal defense responses: a multi-modality analysis
Authors: Choi Tae-jun , Lee Honggu 
Published: December 2020

AbstractDefense responses are a highly conserved behavioral response set across species. Defense responses motivate organisms to detect and react to threats and potential danger as a precursor to anxiety. Accurate measurement of temporal defense responses is important for understanding clinical anxiety and mood disorders, such as post-traumatic stress disorder, obsessive compulsive disorder, and generalized anxiety disorder. Within these conditions, anxiety is defined as a state of prolonged defense response elicitation to a threat that is ambiguous or unspecific. In this study, we aimed to develop a data-driven approach to capture temporal defense response elicitation through a multi-modality data analysis of physiological signals, including electroencephalogram (EEG), electrocardiogram (ECG), and eye-tracking information. A fear conditioning paradigm was adopted to develop a defense response classification model. From a classification model based on 42 feature sets, a higher order crossing feature set-based model was chosen for further analysis with cross-validation loss of 0.0462 (SEM: 0.0077). To validate our model, we compared predicted defense response occurrence ratios from a comprehensive situation that generates defense responses by watching movie clips with fear awareness and threat existence predictability, which have been reported to correlate with defense response elicitation in previous studies. We observed that defense response occurrence ratios are correlated with threat existence predictability, but not with fear awareness. These results are similar to those of previous studies using comprehensive situations. Our study provides insight into measurement of temporal defense responses via a novel approach, which can improve understanding of anxiety and related clinical disorders for neurobiological and clinical researchers.
Genome-wide DNA mutations inArabidopsisplants after multigenerational exposure to high temperature
Authors: Lu Zhaogeng , Cui Jiawen , Wang Li , Teng Nianjun , Zhang Shoudong , Lam Hon-Ming , Zhu Yingfang , Xiao Siwei , Ke Wensi , Lin Jinxing , Xu Chenwu , Jin Biao 
Published: December 2020

AbstractBackgroundElevated temperatures can cause physiological, biochemical, and molecular responses in plants that can greatly affect their growth and development. Mutations are the most fundamental force driving biological evolution. However, how long-term elevations in temperature influence the accumulation of mutations in plants remains unknown.ResultsHere we report that multigenerational exposure ofArabidopsisto extreme heat and moderate warming resulted in significantly increased mutation rates in single-nucleotide variants (SNVs) and small indels. We observed distinctive mutational spectra under extreme and moderately elevated temperatures, with significant increases in transition (C:G→T:A) and transversion (A:T→T:A) frequencies. Mutation occurred more frequently in intergenic regions, coding regions (especially nonsynonymous mutations), and transposable elements (TEs). At elevated temperatures, more mutations accumulated in genes associated with defense responses, DNA repair, and signaling, including the transcriptional response–related genesHSP70andHSFA1A. Methylation was observed more frequently at mutation sites, indicating that it contributed significantly to the mutation process at elevated temperatures. Moreover, the mutations in lines and populations grown under elevated temperatures were significantly biased toward low gene density regions, special trinucleotides (GC context), tandem repeats, and adjacent simple repeats. Additionally, 24% (n= 64) of SNVs and 43% (n= 40) of indels found in all mutation accumulation lines overlapped significantly with genetic variations reported in 1001 Genomes, suggesting a non-uniform distribution of de novo mutations through the genome.ConclusionCollectively, our results suggest that elevated temperatures can accelerate the accumulation, and alter the molecular profiles, of DNA mutations in plants, thus providing significant insight into how environmental temperatures fuel plant evolution.