bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inducing vulnerability to InhA inhibition restores isoniazid susceptibility in drug resistantMycobacterium tuberculosis
Authors: Harrison Gregory A. , Cho Kevin , Wang Erin R. , Sarkar Souvik , Almqvist Fredrik , Patti Gary J. , Stallings Christina L. 
Published: February 2023

AbstractOf the approximately 10 million cases ofMycobacterium tuberculosis(Mtb) infections each year, over 10% are resistant to the frontline antibiotic isoniazid (INH). INH resistance is predominantly caused by mutations that decrease the activity of the bacterial enzyme KatG, which mediates conversion of the pro-drug INH to its active form INH-NAD. We previously discovered an inhibitor ofMtbrespiration, C10, that enhances the bactericidal activity of INH, prevents the emergence of INH-resistant mutants, and re-sensitizes a collection of INH-resistant mutants to INH through an unknown mechanism. To investigate the mechanism of action of C10, we exploited the toxicity of high concentrations of C10 to select for resistant mutants. We discovered two mutations that confer resistance to the disruption of energy metabolism and allow for growth ofMtbin high C10 concentrations, indicating that growth inhibition by C10 is associated with inhibition of respiration. Using these mutants as well as direct inhibitors of theMtbelectron transport chain, we provide evidence that inhibition of energy metabolism by C10 is neither sufficient nor necessary to potentiate killing by INH. Instead, we find that C10 acts downstream of INH-NAD synthesis, causingMtbto become particularly sensitive to inhibition of the INH-NAD target, InhA, without changing the concentration of INH-NAD or the activity of InhA, the two predominant mechanisms of potentiating INH. Our studies revealed that there exists a vulnerability inMtbthat can be exploited to renderMtbsensitive to otherwise subinhibitory concentrations of InhA inhibitor.SignificanceIsoniazid (INH) is a critical frontline antibiotic to treatMycobacterium tuberculosis(Mtb) infections. INH efficacy is limited by its suboptimal penetration of theMtb-containing lesion and by the prevalence of clinical INH-resistance. We previously discovered a compound, C10, that enhances the bactericidal activity of INH, prevents the emergence of INH-resistant mutants, and re-sensitizes a set of INH-resistant mutants to INH. Resistance is typically mediated bykatGmutations that decrease the activation of INH, which is required for INH to inhibit the essential enzyme InhA. Our current work demonstrates that C10 re-sensitizes INH-resistantkatG-hypomorphs without enhancing the activation of INH. We furthermore show that C10 causesMtbto become particularly vulnerable to InhA inhibition without compromising InhA activity on its own. Therefore, C10 represents a novel strategy to curtail the development of INH resistance and to sensitizeMtbto sub-lethal doses of INH, such as those achieved at the infection site.
Why Clinical Trials Stop: The Role of Genetics
Authors: Razuvayevskaya Olesya , Lopez Irene , Dunham Ian , Ochoa David 
Published: February 2023

AbstractMany drug discovery projects are started, but few progress fully through clinical trials to approval. Previous work has shown that human genetics support for the therapeutic hypothesis increases the chance of trial progression. Here, we applied natural language processing to classify the freetext reasons for 28,842 clinical trials that stopped before their endpoints were met. We then evaluated these classes in the light of the underlying evidence for the therapeutic hypothesis and target properties. We show that trials are more likely to stop due to lack of efficacy in the absence of strong genetic evidence from human populations or genetically-modified animal models. Furthermore, trials are more likely to stop for safety reasons if the drug target gene is highly constrained in human populations and if the gene is not selectively expressed. These results support the growing use of human genetics to evaluate targets for drug discovery programmes.
Gender differences in Pornography Use and Associated Factors among high school students: A Cross-Sectional Study
Authors: Mahmoud Ali Jotyar , Abdulqadir Hajar Hassan , Khalid Rojeen Chalabi , Dirbas Vindad Hashim , Hasan Doaa Farhad , Mahfodh Saman Sherwan , Naisan Kareen Yarwant , Arif Iman Mohammed , Yousif Iman Ramadhan , Mohammed Sana Najeeb , Haji Suzan Muhsin , Mohammed Suzan Taha , Hama Ali Alind Ari , Babakhani Siavash 
Published: February 2023

AbstractBackground and aimThe pornography consuming is increasing through the availability of the internet worldwide and the availability of the pornographic sites without any restriction, pornographic sites have many complications in the consumer and lacking survey in our country which make sense to conduct this study. This study aimed to measure the prevalence of pornography watching among high school students and factors associated with pornography viewing.Materials and MethodsThis cross-sectional study was conducted at Zakho independent administration, Kurdistan Region, Iraq among 5 different high school students and 2 institutions. This survey was conducted using a paper questionnaire administered to the participants between April and July 2022. Chi-square analysis was performed to identify possible risk factors for viewing porn and results were expressed as a p valueResultsTotal number of the participants included in this study was 921 with an average age ± standard deviation (SD) of 16.78 years ±1.26. More than half of participants was male (54.83%), viewed pornography alone (49.08%) and about 69.71% disagree on watching porn. There were statistically significant differences (p <0.001) in the attitude and practice of men compared with women throughout all tested variables. About 50.71% of the participants were viewed pornography at least once in a lifetime, among those 65.1% are male and 34.9% of them are female and 92.55% of participants agree to close pornography sitesConclusionThe prevalence of pornography among high school students is high. Young age, and male gender are predictors for higher pornography viewing and should be considered when designing public health intervention in a related context. Longitudinal studies for investigating pornography consumption among different educational levels are needed to assess the causal relationship between pornography consumption and associated factors.
Diagnostic Machine Learning Applications on Clinical Populations using Functional Near Infrared Spectroscopy: A Review
Authors: Eken Aykut , Nassehi Farhad , Eroğul Osman 
Published: February 2023

AbstractFunctional near-infrared spectroscopy (fNIRS) and its interaction with machine learning (ML) is a popular research topic for the diagnostic classification of clinical disorders due to the lack of robust and objective biomarkers. This review provides an overview of research on psychiatric diseases by using fNIRS and ML. Article search was carried out and 45 studies were evaluated by considering their sample sizes, used features, ML methodology, and reported accuracy. To our best knowledge, this is the first review that reports diagnostic ML applications using fNIRS. We found that there has been an increasing trend to perform ML applications on fNIRS-based biomarker research since 2010. The most studied populations are schizophrenia (n=12), attention deficit and hyperactivity disorder (n=7), and autism spectrum disorder (n=6) are the most studied populations. There is a significant negative correlation between sample size (>20) and accuracy values. Support vector machine (SVM) and deep learning (DL) approaches were the most popular classifier approaches (SVM = 20) (DL = 10). Eight of these studies recruited a number of participants more than 100 for classification. Change in oxy-hemoglobin (ΔHbO) based features were used more than change in deoxy-hemoglobin-based ones and the most popular ΔHbO-based features were mean ΔHbO (n=11) and ΔHbO-based functional connections (n=11). Using ML on fNIRS data might be a promising approach to reveal specific biomarkers for diagnostic classification.
Total and regional skeletal muscle mass references by sport participation and body size in youth
Authors: Correas-Gómez Lorena , Alvero-Cruz José Ramón , Barrera-Expósito Jesús , de Albornoz-Gil Margarita Carrillo , Quitério Ana L. , Carnero Elvis A. 
Published: February 2023

AbstractSkeletal muscle mass (SMM) is a relevant indicator of adolescent health influenced by sport participation, body size, and maturation. However, limited data are available from techniques accessible to field professionals.PurposeTo provide reference data of regional and total-body SMM and fat-free mass (FFM) derived from anthropometry among groups of age, sex, and sport participation in healthy Caucasian children and adolescents.Materials and methodsA cross-sectional dataset of 1,438 participants aged 8-18 years were analyzed for this study. Regional and total-body SMM and FFM were estimated from anthropometric variables. Sport participation was obtained byad hocquestionnaires and maturity offset was calculated using predictive equations. General linear model of mixed factors was used to analyze the variance of FFM or SMM across groups and confounders. Ln-ln regression analysis was applied to describe the scaling relationship between SMM and height.ResultsPositive interactions were found between sex, sport participation, and age for regional muscle variables (P<0.05). Adjusted total and regional SMM significantly increased along school-age periods in the active groups (∼2.2 kg gain,P<0.05, boys and girls; arm, ∼1.3 cm gain,P<0.01, boys), and allometric values were higher in boys than girls for regional muscle (P<0.01).DiscussionThe novel contribution of this analysis includes regional indicators of SMM and the relevance of sport participation on SMM accrual in post-pubertal boys. Also, confirms that muscle growth rate varies across sex and phases of puberty, which arises a plausible sexual phenotype/dysmorphism of regional SMM influenced by sport participation.
Modification of gene expression after internalization of Growth Hormone (GH) into the cell nucleus
Authors: Morel Gerard 
Published: February 2023

ABSTRACTGrowth hormone (GH) and many other hormones or growth factors have been shown to be rapidly internalized and translocated into the nucleus. The first event of peptide action is binding to its receptor which initiates both signal transduction pathways and internalization. The latter process involves the nucleus and probably gene transcription. In order to analyze the consequences of internalization of GH on gene expression, we used different populations of CHO cells, transfected with either full length GH receptor, or with defective receptor unable to trigger either signal transduction (deletion of box1) or the internalization of GH (Phe346mutation in Ala). In addition, functional isolated nuclei were incubated 10 and 30 min with 50 nM GH in order to analyze the direct effect of GH on gene expression without surrounding cytoplasmic structures. The genes involved in signal transduction pathways were not revealed if GH internalization is the only functional activity in the whole cell as well as with isolated nuclei. In intact cell, internalization increased expression of 297 genes and decreased fewer than 10% of those known to be influenced by GH. Variations of expression in purified nuclei showed large variations with time. If cell signaling was not modified, cellular growth and proliferation, nucleic acid metabolism, cellular development, cell cycle and gene expression showed many variations with time. GH internalization shows direct effects on gene expression, different from those stimulated by signal transduction.
A General Fluorescence-Based Method for Quantifying and Mapping Biomolecular Polarity In Vitro and In Cells
Authors: Owyong Tze Cin , O’Shea Riley , Lee Mihwa , White Jonathan M. , Donnelly Paul S. , Hinde Elizabeth , Wong Wallace W. H. , Hong Yuning 
Published: February 2023

AbstractSpatial discretization of biomolecules in the complex cellular environment is crucial for biomolecular form and function. The ability to better understand the driving force of spatial discretization of biomolecules in the complex cellular matrix remains a challenging task. We report on the robust polarity sensitive solvatochromic probe,FLAM, in conjunction with spectral phasor analysis as a general method for studying environmental polarity in biological systems. We find that phase separated proteins of SFPQ have distinct polarity depending on the type of phase separation occurring, suggesting that polarity plays a role in the formation of phase separated condensates. When usingFLAMin cells, distinct subcellular environmental polarity distribution but similar trend of changes is observed for cells under similar type of stressors. Taken together, our method puts forth an exciting development in the tool set for the study of phase separation.
Ferroptosis is determined by chloride ions
Authors: Huang Dichun , Dai Zhangshuai , Wang Chao , Mai Haiying , Zhao Junyi , Cao Lingbo , Wang Sijie , Dai Zhun , Xu Kun , He Ronghan , Zhu Shaoshen , Chen Yanchen , Bing Tiejun , Zhu Xinzhou , Chew Ting Gang , Huang Junqi 
Published: February 2023

AbstractFerroptosis has emerged as a deliberate type of programmed cell death that manifests marked importance ubiquitously in health and diseases. However, after a decade of research, the mechanisms of ferroptosis execution remain unclear. Here we identify chloride ions (Cl-) as essential determinants of ferroptosis. Water homeostasis manipulated by extracellular solute concentration disrupts ferroptotic cell death. Hyperosmotic stress attenuates ferroptosis and endues cells with high lipid peroxidation. Analyses of a fluorescent chloride probe show that Cl-fluxes into the cytoplasm during ferroptosis, substantiating a role for Cl-to drive water flow. Depletion of extracellular chloride ions ([Cl-]o) from culture media congruously confers resistance to ferroptosis. The [Cl-]o-depleted ferroptotic cells fall into two populations: cells with low lipid peroxidation; cells with high lipid peroxidation but not cell swelling or cell rupture. Contrarily, solitary [Cl-]ooverload is sufficient to elicit ferroptosis without canonical ferroptosis inducers. Further experiments show that ferroptotic cells depolarize and [Cl-]ois positively correlated with this process. Membrane depolarization upregulates the level of lipid peroxidation, suggesting that membrane potential may be a universal mechanism governing ferroptosis. Together, our findings reveal that ferroptosis is determined by chloride ions.
Plant spectral diversity from high-resolution multispectral imagery detects functional diversity patterns in coastal dune communities
Authors: Beccari Eleonora , Carmona Carlos Pérez , Tordoni Enrico , Petruzzellis Francesco , Martinucci Davide , Casagrande Giulia , Pavanetto Nicola , Rocchini Duccio , D’Antraccoli Marco , Ciccarelli Daniela , Bacaro Giovanni 
Published: February 2023

SummaryRemote sensing is a fundamental tool to monitor biodiversity over large spatial extents. However, it is still not clear whether spectral diversity (SD - variation of spectral response across a set of pixels) may represent a fast and reliable proxy for different biodiversity facets such as taxonomic (TD) and functional diversity (FD) across different spatial scales.We used fine resolution (3 cm) multispectral imagery on coastal dune communities in Italy to explore SD patterns across spatial scales and assess SD relationships with TD and FD along the environmental gradient.We measured TD as species richness, while SD and FD were computed using probability densities functions based on pixels and species position in multivariate spaces based on pixel values and traits, respectively. We assessed how SD is related to TD and FD, we compared SD and FD patterns in multivariate space occupation, and we explored diversity patterns across spatial scales using additive partitioning (i.e., plot, transect, and study area).We found a strong correspondence between the patterns of occupation of the functional and spectral spaces and significant relationships were found along the environmental gradient. TD showed no significant relationships with SD. However, TD and SD showed higher variation at broader scale while most of FD variation occurred at plot level.By measuring FD and SD with a common methodological framework, we demonstrate the potential of SD in approximating functional patterns in plant communities. We show that SD can retrieve information about FD at very small scale, which would otherwise require very intensive sampling efforts. Overall, we show that SD retrieved using high resolution images is able to capture different aspects of FD, so that the occupation of the spectral space is analogous to the occupation of the functional space. Studying the occupation of both spectral and functional space brings a more comprehensive understanding of the factors that influence the distribution and abundance of plant species across environmental gradients.
RxRx3: Phenomics Map of Biology
Authors: Fay Marta M. , Kraus Oren , Victors Mason , Arumugam Lakshmanan , Vuggumudi Kamal , Urbanik John , Hansen Kyle , Celik Safiye , Cernek Nico , Jagannathan Ganesh , Christensen Jordan , Earnshaw Berton A. , Haque Imran S. , Mabey Ben 
Published: February 2023

AbstractThe combination of modern genetic perturbation techniques with high content screening has enabled genome-scale cell microscopy experiments that can be leveraged to constructmaps of biology. These are built by processing microscopy images to produce readouts in unified and relatable representation space to capture known biological relationships and discover new ones. To further enable the scientific community to develop methods and insights from map-scale data, here we releaseRxRx3, the first ever public high-content screening dataset combining genome-scale CRISPR knockouts with multiple-concentration screening of small molecules (a set of FDA approved and commercially available bioactive compounds). The dataset contains 6-channel fluorescent microscopy images and associated deep learning embeddings from over 2.2 million wells that span 17,063 CRISPR knockouts and 1,674 compounds at 8 doses each.RxRx3is one of the largest collections of cellular screening data, and as far as we know, the largest generated consistently via a common experimental protocol within a single laboratory. Our goal in releasingRxRx3is to demonstrate the benefits of generating consistent data, enable the development of the machine learning methods on this scale of data and to foster research, methods development, and collaboration.For more information aboutRxRx3please visit RxRx.ai/rxrx3
Target-specific requirements for RNA interference can arise through restricted RNA amplification despite the lack of specialized pathways
Authors: Knudsen-Palmer Daphne R. , Raman Pravrutha , Ettefa Farida , De Ravin Laura , Jose Antony M. 
Published: February 2023

ABSTRACTSince double-stranded RNA (dsRNA) is effective for silencing a wide variety of genes, all genes are typically considered equivalent targets for such RNA interference (RNAi). Yet, loss of some regulators of RNAi in the nematodeC. eleganscan selectively impair the silencing of some genes. Here we show that such selective requirements can be explained by an intersecting network of regulators acting on genes with differences in their RNA metabolism. In this network, the Maelstrom domain-containing protein RDE-10, the intrinsically disordered protein MUT-16, and the Argonaute protein NRDE-3 work together so that any two are required for silencing one somatic gene, but each is singly required for silencing another somatic gene, where only the requirement for NRDE-3 can be overcome by enhanced dsRNA processing. Quantitative models and their exploratory simulations led us to find that (1) changingcis-regulatory elements of the target gene can reduce the dependence on NRDE-3, (2) animals can recover from silencing in non-dividing cells and (3) cleavage and tailing of mRNAs with UG dinucleotides, which makes them templates for amplifying small RNAs, is enriched within ‘pUG zones’ matching the dsRNA. Similar crosstalk between pathways and restricted amplification could result in apparently selective silencing by endogenous RNAs.
Behavioral and neural evidence for the underestimated attractiveness of faces synthesized using an artificial neural network
Authors: Nishida Satoshi 
Published: February 2023

AbstractDespite recent advantages in artificial intelligence (AI), the potential human aversion to AI has not been dispelled yet. If such aversion degrades the human preference to AI-synthesized visual information, the preference should be reduced solely by the human belief that the information is synthesized by AI, independently of its appearance. To test this hypothesis, this study designed a task paradigm in which naïve participants rated the attractiveness of various faces synthesized using an artificial neural network, under the fake instruction that half of the faces were synthetic and the other half were real. This design allowed evaluating the effect of participants’ beliefs on their attractiveness ratings separately from the effect of facial appearance. In addition, to investigate the neural substrates of the belief effect, brain responses to faces were collected using fMRI during this task. It is found that participants’ ratings declined when the faces were believed to be synthetic. Furthermore, the belief changed the responsiveness of fMRI signals to facial attractiveness in the right fusiform cortex. These behavioral and neural findings support the notion that the human preference to visual information becomes lower solely due to the beliefs that the information is synthesized by AI.
Neutralization of SARS-CoV-2 BQ.1.1 and XBB.1.5 by Breakthrough Infection Sera from Previous and Current Waves in China
Authors: Wang Xun , Jiang Shuai , Jiang Shujun , Li Xiangnan , Ai Jingwen , Lin Ke , Lv Shiyun , Zhang Shixuan , Li Minghui , He Xinyi , Li Dingding , Li Chen , Zhao Chaoyue , Zhao Xiaoyu , Qiao Rui , Cui Yuchen , Chen Yanjia , Li Jiayan , Cai Guonan , Li Jixi , Dai Lili , Hu Zixin , Zhang Wenhong , Zhang Yanliang , Wang Pengfei 
Published: February 2023

AbstractSARS-CoV-2 is continuing to evolve and diversify, with an array of various Omicron sub-lineages, including BA.5, BA.2.75, BN.1, BF.7, BQ.1, BQ.1.1, XBB and XBB.1.5, now circulating globally at recent time. In this study, we evaluated the neutralization sensitivity of a comprehensive panel of Omicron subvariants to sera from different clinical cohorts, including individuals who received homologous or heterologous booster vaccinations, vaccinated people who had Delta or BA.2 breakthrough infection in previous waves, and patients who had BA.5 or BF.7 breakthrough infection in the current wave in China. All the Omicron subvariants exhibited substantial neutralization evasion, with BQ.1, BQ.1.1, XBB.1, and XBB.1.5 being the strongest escaped subvariants. Sera from Omicron breakthrough infection, especially the recent BA.5 or BF.7 breakthrough infection, exhibited higher neutralizing activity against all Omicron sub-lineages, indicating the chance of BA.5 and BF.7 being entirely replaced by BQ or XBB subvariants in China in a short-term might be low. We also demonstrated that the BQ and XBB subvariants were the most resistant viruses to monoclonal antibodies. Continuing to monitor the immune escape of SARS-CoV-2 emerging variants and developing novel broad-spectrum vaccines and antibodies are still crucial.