bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of miR‐128‐3p through MAPK14 activation in the apoptosis of GC2 spermatocyte cell line following heat stress
Authors: Zou Liping , Cheng Guiping , Xu Chengcheng , Liu Heyu , Wang Yingying , Li Nianyu , Zhu Changhong , Xia Wei 
Published: October 2020

AbstractBackgroundMicroRNAs play a crucial role in the regulation of spermatogenesis. For example, miR‐128‐3p expression is known to decrease significantly after testicular hyperthermia, but the regulatory effect of this change on the spermatogenesis damage caused by heat stress remains unclear.ObjectivesThis study aimed to verify whether the target gene of miR‐128‐3p is MAPK14, which affects spermatogenic cell proliferation and apoptosis under testicular hyperthermia.Materials and methodsMouse testis and GC2 spermatocyte cell line heat stress models were established. miR‐128‐3p expression before and after heat stress was analyzed by reverse transcription polymerase chain reaction. MAPK14 and p‐MAPK14 expression was detected by Western blot, and cell apoptosis was analyzed by Annexin V‐FITC/PI. Subsequently, miR‐128‐3p inhibitors and mimics were used to interfere with spermatocytes before and after heat stress, respectively, for correlation detection.ResultsCompared with the control group, the heat stress group showed decreased miR‐128‐3p expression, increased p‐MAPK14 expression, and decreased cell proliferation activity. In the GC2‐spd cell line in vitro, miR‐128‐3p inhibitors were found to upregulate p‐MAPK14 expression, reduce cell proliferation activity, and increase apoptosis, consistent with the results obtained in the heat treatment alone. Furthermore, miR‐128‐3p mimics transfected in the GC2 cells after heat stress reduced p‐MAPK14 expression, alleviated the decrease in cell proliferation, and decreased the apoptosis level.ConclusionsThe downregulation of miR‐128‐3p expression plays an important role in spermatogenesis damages after testicular hyperthermia, which is probably attributable to the activation of the MAPK signaling pathway. Downregulated miR‐128‐3p expression induces the apoptosis and inhibits the proliferation of spermatogenic cells by promoting MAPK14 phosphorylation.
Bystanders and ethical review of research: Proceed with caution
Authors: Wikler Daniel 
Published: October 2020

AbstractScientists seeking to conduct research with human subjects must first submit their proposals to research ethics committees (Institutional Review Boards [IRBs], in the United States). Some of these studies pose risks to “bystanders,” i.e., people who may be affected by the research but who are not enrolled as study subjects. Should IRBs expand their scope to include oversight over possible harms to bystanders as well as research subjects? This paper presents arguments against this step. Prior review of research with human subjects, despite its evident burden on the research enterprise, is a necessary caution, because the tension between the objectives of humane treatment of research subjects and sound scientific design and procedure has in the past led to serious abuses. This rationale is inapplicable in the case of bystanders. Moreover, in view of the many and varied effects of both research practices and scientific advances on the broader public over time, those who may be considered to be “bystanders” may potentially expand without limit; requiring IRBs to anticipate these distant and long‐term effects as part of prior ethical review could greatly increase its burden and its deterrent effect on research. While conducting research without concern for serious potential harm to bystanders may be irresponsible and unethical, expanding the scope of prior review by IRBs to include risks to bystanders is not required by the principles governing human subjects research, and the costs and burdens of this expansion may outweigh any expected gains.
Inhibition of microRNA let‐7b expression by KDM2B promotes cancer progression by targeting EZH2 in ovarian cancer
Authors: Kuang Yan , Xu Hong , Lu Fangfang , Meng Jiahua , Yi Yeye , Yang Huilan , Hou Hairui , Wei Hao , Su Shanheng 
Published: October 2020

AbstractMicroRNA let‐7b is a potent tumor suppressor and targets crucial oncogenes. Previous studies have shown that let‐7b expression is suppressed in ovarian cancer; however, the regulatory mechanisms of let‐7b in ovarian cancer are still not well defined. The cellular role and targets of let‐7b in ovarian cancer remain elusive. In the present study, we showed that histone demethylase, KDM2B, directly suppressed let‐7b expression by H3K36me2 demethylation. Moreover, let‐7b inhibited EZH2 expression in ovarian cancer cells. Based on these results we know that let‐7b antagonizes the enhancement of EZH2 expression caused by KDM2B overexpression, and its expression is negatively correlated with KDM2B and EZH2 expression. More importantly, proliferation, migration, and wound healing assays showed that let‐7b inhibited ovarian cancer cell proliferation and migration in vitro. Additionally, let‐7b overexpression neutralized KDM2B‐promoted cell proliferation and migration. Furthermore, downregulation of let‐7b increased the xenografted tumor volumes in nude mice that were transplanted with KDM2B‐silenced cells. EZH2 silencing reversed the tumor growth enhancement mediated by inhibition of let‐7b. Last, we show that let‐7b expression is suppressed in ovarian carcinomas and its expression is negatively associated with the clinicopathological features of ovarian cancer, including histological type, histological grade, International Federation of Gynecology and Obstetrics (FIGO) stage, and lymph node metastatic status. In conclusion, in ovarian cancer, let‐7b expression is epigenetically suppressed by high expression of KDM2B. The loss of let‐7b upregulates the expression of EZH2, which promotes ovarian cancer growth in vitro and in vivo.
Vestibular phenotype‐genotype correlation in a cohort of 90 patients with Usher syndrome
Authors: Wafa Talah T. , Faridi Rabia , King Kelly A. , Zalewski Christopher , Yousaf Rizwan , Schultz Julie M. , Morell Robert J. , Muskett Julie , Turriff Amy , Tsilou Ekaterini , Griffith Andrew J. , Friedman Thomas B. , Zein Wadih M. , Brewer Carmen C. 
Published: October 2020

AbstractUsher syndrome has been historically categorized into one of three classical types based on the patient phenotype. However, the vestibular phenotype does not infallibly predict which Usher genes are mutated. Conversely, the Usher syndrome genotype is not sufficient to reliably predict vestibular function. Here we present a characterization of the vestibular phenotype of 90 patients with clinical presentation of Usher syndrome (59 females), aged 10.9 to 75.5 years, with genetic variants in eight Usher syndromic genes and expand the description of atypical Usher syndrome. We identified unexpected horizontal semicircular canal reactivity in response to caloric and rotational stimuli in 12.5% (3 of 24) and 41.7% (10 of 24), respectively, of our USH1 cohort. These findings are not consistent with the classical phenotypic definition of vestibular areflexia in USH1. Similarly, 17% (6 of 35) of our cohort with USH2A mutations had saccular dysfunction as evidenced by absent cervical vestibular evoked myogenic potentials in contradiction to the classical assumption of normal vestibular function. The surprising lack of consistent genotypic to vestibular phenotypic findings as well as no clear vestibular phenotypic patterns among atypical USH cases, indicate that even rigorous vestibular phenotyping data will not reliably differentiate the three USH types.
Estimating uncertainty in deep learning for reporting confidence to clinicians in medical image segmentation and diseases detection
Authors: Ghoshal Biraja , Tucker Allan , Sanghera Bal , Lup Wong Wai 
Published: October 2020

AbstractDeep learning (DL), which involves powerful black box predictors, has achieved a remarkable performance in medical image analysis, such as segmentation and classification for diagnosis. However, in spite of these successes, these methods focus exclusively on improving the accuracy of point predictions without assessing the quality of their outputs. Knowing how much confidence there is in a prediction is essential for gaining clinicians' trust in the technology. In this article, we propose an uncertainty estimation framework, called MC‐DropWeights, to approximate Bayesian inference in DL by imposing a Bernoulli distribution on the incoming or outgoing weights of the model, including neurones. We demonstrate that by decomposing predictive probabilities into two main types of uncertainty, aleatoric and epistemic, using the Bayesian Residual U‐Net (BRUNet) in image segmentation. Approximation methods in Bayesian DL suffer from the “mode collapse” phenomenon in variational inference. To address this problem, we propose a model which Ensembles of Monte‐Carlo DropWeights by varying the DropWeights rate. In segmentation, we introduce a predictive uncertainty estimator, which takes the mean of the standard deviations of the class probabilities associated with every class. However, in classification, we need an alternative approach since the predictive probabilities from a forward pass through the model does not capture uncertainty. The entropy of the predictive distribution is a measure of uncertainty, but its exponential depends on sample size. The plug‐in estimate in mutual information is subject to sampling bias. We propose Jackknife resampling, to correct for sample bias, which improves estimating uncertainty quality in image classification. We demonstrate that our deep ensemble MC‐DropWeights method, using the bias‐corrected estimator produces an equally good or better result in both quantified uncertainty estimation and quality of uncertainty estimates than approximate Bayesian neural networks in practice.
Development of spatial biases in school‐aged children
Authors: Hoyos Patricia M. , Kim Na Yeon , Cheng Debby , Finkelston Abigail , Kastner Sabine 
Published: October 2020

AbstractIn the adult brain, biases in the allocation of spatial attention can be measured using a line bisection task and are directly relatable to neural attention signals in the fronto‐parietal attention network. Behavioral studies on the development of spatial biases have yielded a host of inconsistent results, likely due to variance in sample size, definition of experimental groups, and motor confounds introduced by using a paper‐and‐pencil version of a line bisection task. Here, we used a perceptual, computerized version of this task and examined the development of spatial biases in 459 children from grades 1–8 and 61 college freshmen. We found that children in early elementary grades exerted a significant leftward bias that gradually diminished with advancing grade level. We further show that among children in early elementary school grades, the degree of leftward spatial bias predicted better performance on a rapid automatized naming test, a predictor of reading ability. Significant leftward biases in early elementary school grades may be due to reading experience, thereby reflecting an interaction of the attention network with the evolving reading network.
Tune in to the right frequency: Theta changes when distancing from emotions elicited by unpleasant images and words
Authors: Sulpizio Simone , Grecucci Alessandro , Job Remo 
Published: October 2020

AbstractEmotion regulation allows humans to successfully modulate their reactions to life events. Whether regulation strategies may alter brain oscillatory activity and how they are influenced by format and emotional dimensions is still under debate. We investigated oscillatory brain dynamics during the implementation of the strategy of Distancing and during the regulation of the emotions elicited by neutral and unpleasant pictures and, for the first time, words. When implementing the strategy, an early increase in theta band in posterior regions was observed (Effect of Strategy). We interpret this effect as a marker of emotion regulation, and we suggest an integrative framework of the role of theta on regulatory processes. When regulating the emotional impact elicited by stimuli, a decrease in the theta and beta bands in posterior regions for pictures, but not for words, was observed (Effect of Regulation). Behaviorally, the Effect of Regulation was evident for both pictures and words and more pronounced for Valence than for Arousal. These results contribute to better understand the neural and behavioral features of Distancing (both Effect of Strategy and of Regulation), and open up the possibility to clarify which strategy works better to modulate specific stimulus types and emotional dimensions.
Measuring the quality of scientific references in Wikipedia: an analysis of more than 115M citations to over 800 000 scientific articles
Authors: Nicholson Joshua M. , Uppala Ashish , Sieber Matthias , Grabitz Peter , Mordaunt Milo , Rife Sean C. 
Published: October 2020

Wikipedia is a widely used online reference work which cites hundreds of thousands of scientific articles across its entries. The quality of these citations has not been previously measured, and such measurements have a bearing on the reliability and quality of the scientific portions of this reference work. Using a novel technique, a massive database of qualitatively described citations, and machine learning algorithms, we analyzed 1 923 575 Wikipedia articles which cited a total of 824 298 scientific articles in our database and found that most scientific articles cited by Wikipedia articles are uncited or untested by subsequent studies, and the remainder show a wide variability in contradicting or supporting evidence. Additionally, we analyzed 51 804 643 scientific articles from journals indexed in the Web of Science and found that similarly most were uncited or untested by subsequent studies, while the remainder show a wide variability in contradicting or supporting evidence.
Estimating probabilistic site‐specific species pools and dark diversity from co‐occurrence data
Authors: Carmona Carlos P. , Pärtel Meelis 
Published: October 2020

AbstractAimThe species pool specific for a site includes all species from the region that are theoretically able to live in the site's particular ecological conditions. The absent portion of the site‐specific species pool forms the site’s dark diversity, which is unobservable and can only be estimated. Most existing methods to designate dark diversity act in a binary fashion. Here, we argue that the species pool is more suitably defined as a fuzzy set, present a method to estimate probabilistic species pools using pairwise co‐occurrence data with a hypergeometric distribution, and compare it with established methods (Beals index and favourability correction).InnovationWe compare the different aspects of the method’s performance using simulations based on individual agents in which the suitability for each species in each site is known. Further, we assessed the methods in two real datasets with nested sampling designs. We provide the R package ‘DarkDiv’ (https://cran.r‐project.org/web/packages/DarkDiv/index.html) that implements all the compared methods for estimations of probabilistic dark diversity and species pools.Main conclusionsBeals method is extremely sensitive to species frequency, and predicts species’ suitability to local conditions less accurately than the other considered methods. The favourability transformation corrected this relationship, but still predicted extremely low probabilities for species with very little information. The hypergeometric method outperformed the Beals and favourability methods in all considered aspects in the simulations and displayed better characteristics in the real datasets. The hypergeometric method is currently the best option to estimate probabilistic dark diversity and species pool composition based on pairwise species co‐occurrence data.
Survey of the antimicrobial resistance of Helicobacter pylori in France in 2018 and evolution during the previous 5 years
Authors: Mégraud Francis , Alix Chloé , Charron Paul , Bénéjat Lucie , Ducournau Astrid , Bessède Emilie , Lehours Philippe 
Published: October 2020

AbstractBackground and ObjectivesSurveillance of Helicobacter pylori resistance to antibiotics was carried out in France in 2014, 2016, and 2018. We report here the results of the 2018 survey as well as the evolution over the 5‐year period.Materials and MethodsIn this observational study, gastric biopsies were obtained by 62 gastroenterologists randomly selected in 5 regions of France and sent to a central laboratory where culture, antimicrobial susceptibility testing, and a real‐time PCR were performed in order to detect H pylori and its mutations associated with clarithromycin resistance.Results and ConclusionDuring the year 2018, 951 patients were included: 55.3% women, mean age: 52.4 years ± 15.7, 71.6% born in France. Among them, 359 patients were H pylori positive by both culture and real‐time PCR, and 7 more by PCR only. There were 244 naive patients, 110 previously treated patients, and unknown for 5. Primary resistance to clarithromycin was 20.9% [16.3‐26.4], to levofloxacin 17.6% [13.4‐22.9], and to metronidazole 58.6% [52.3%‐64.6%]. Secondary resistance for these antibiotics was 56.4%, 22.7%, and 87.3%, respectively. There was no resistance to amoxicillin and tetracycline and very low resistance to rifampicin (1.2%) in both naive and treated patients. Primary resistance to clarithromycin decreased from 22.2% to 20.3% between 2014 and 2016, and appears to be stable since then. This can be linked to a stable consumption of macrolides over the 3‐year time period. Primary levofloxacin resistance was relatively stable while metronidazole resistance increased. Interestingly, in both naive and treated patients, amoxicillin and rifampicin resistance were rare.
Impact of temporal rainfall patterns on flash floods in Hue City, Vietnam
Authors: Mu Dengrui , Luo Pingping , Lyu Jiqiang , Zhou Meimei , Huo Aidi , Duan Weili , Nover Daniel , He Bin , Zhao Xiaoli 
Published: October 2020

AbstractUrban flooding is a perennial problem, especially in developing countries with relatively weak infrastructure under ever‐increasing stress due to climate change and human activities. We simulate the temporally variable flood‐water depth and inundation area under four designed rainfall patterns in the typical tropical rainforest city of Hue, Vietnam. The four rainfall types are R1 (peak at fifth hour), R2 (peak at 20th hour), R3 (peak at first hour), and R4 (peak at 13th hour). Results show that temporal rainfall pattern R4 with peak rainfall in the middle of the total period yielded the maximum water depth of 1.88 m. R3, with peak rainfall in the first hour, yields the shallowest maximum water depth and the largest inundation extent. When the water depth for R3 is 0.1–0.2 m, the inundated area caused by R3 is 3–4 times that of the other three patterns. Analysis of urban flood inundation in Hue provides a management tool to facilitate flood risk management in the context of extreme rainfall.
Prognostic value of anti‐HBc quantification in hepatitis B virus related acute‐on‐chronic liver failure
Authors: Li Jing , Gong Qi‐ming , Xie Pei‐lin , Lin Jun‐yu , Chen Jia , Wei Dong , Yu De‐min , Han Yue , Zhang Xin‐xin 
Published: October 2020

AbstractBackground and AimIt has been reported that serum quantification of anti‐HBc (qAnti‐HBc) could predict antiviral response in chronic hepatitis B (CHB) patients, while its role in hepatitis B virus‐related acute‐on‐chronic liver failure (HBV‐ACLF) remains unclear. Its implication in HBV‐ACLF was evaluated in this study.MethodsBaseline serum qAnti‐HBc levels were retrospectively detected in HBV‐ACLF and CHB patients using recently developed double‐sandwich immunoassay. The association of qAnti‐HBc level with clinical outcomes was evaluated by multiple logistic regression. Nomogram was adopted to formulate an algorithm incorporating qAnti‐HBc for the prediction of survival in HBV‐ACLF. The post‐hospitalization of HBV‐ACLF patients were followed‐up for 1 year.ResultsEighty‐eight HBV‐ACLF as training set, 80 HBV‐ACLF as validation set and 216 CHB cases were included. Serum qAnti‐HBc level was significantly higher in HBV‐ACLF (4.95 ± 0.54 log10 IU/mL) than CHB patients (4.47 ± 0.84 log10 IU/mL) (P < 0.01). Among HBV‐ACLF cases, both in training and validation set, patients with poor outcomes had lower qAnti‐HBc level. Area under receiver operating characteristic curve of the novel qAnti‐HBc inclusive model was 0.82, superior to 0.73 from model for end‐stage liver disease scores (P = 0.018), which was confirmed in validation set. During follow‐up, the qAnti‐HBc level declined at month 3 and month 6, then plateaued at 3.84 log10 IU/mL.ConclusionsSerum qAnti‐HBc level was associated with disease severity and might be served as a novel biomarker in the prediction of HBV‐ACLF clinical outcomes. The underlying immunological mechanism warrants further investigation.
The pharmacokinetic/pharmacodynamic paradigm for antimicrobial drugs in veterinary medicine: Recent advances and critical appraisal
Authors: Toutain Pierre‐Louis , Pelligand Ludovic , Lees Peter , Bousquet‐Mélou Alain , Ferran Aude A. , Turnidge John D. 
Published: October 2020

AbstractPharmacokinetic/pharmacodynamic (PK/PD) modelling is the initial step in the semi‐mechanistic approach for optimizing dosage regimens for systemically acting antimicrobial drugs (AMDs). Numerical values of PK/PD indices are used to predict dose and dosing interval on a rational basis followed by confirmation in clinical trials. The value of PK/PD indices lies in their universal applicability amongst animal species. Two PK/PD indices are routinely used in veterinary medicine, the ratio of the area under the curve of the free drug plasma concentration to the minimum inhibitory concentration (MIC) (fAUC/MIC) and the time that free plasma concentration exceeds the MIC over the dosing interval (fT > MIC). The basic concepts of PK/PD modelling of AMDs were established some 20 years ago. Earlier studies have been reviewed previously and are not reconsidered in this review. This review describes and provides a critical appraisal of more recent, advanced PK/PD approaches, with particular reference to their application in veterinary medicine. Also discussed are some hypotheses and new areas for future developments.First,a brief overview of PK/PD principles is presented as the basis for then reviewing more advanced mechanistic considerations on the precise nature of selected indices. Then, several new approaches to selecting PK/PD indices and establishing their numerical values are reviewed, including (a) the modelling of time–kill curves and (b) the use of population PK investigations. PK/PD indices can be used for dose determination, and they are required to establish clinical breakpoints for antimicrobial susceptibility testing. A particular consideration is given to the precise nature of MIC, because it is pivotal in establishing PK/PD indices, explaining that it is not a “pharmacodynamic parameter” in the usual sense of this term.