bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of seminal polyaromatic hydrocarbons exposome with idiopathic male factor infertility: A proteomic insight into sperm function
Authors: Nayak Jasmine , Jena Soumya Ranjan , Kumar Sugandh , Kar Sujata , Dixit Anshuman , Samanta Luna 
Published: March 2022

AbstractOxidative stress (OS) is implicated in 80% of idiopathic male infertility (IMI) patients where exposure to redox active environmental toxicants such as polyaromatic hydrocarbons (PAHs) may play. In the present study the seminal exposome of various PAH was analyzed in two separate cohorts including 43 fertile donors and 60 IMI patients by HPLC and receiver operator characteristic curve was applied to find out the cut-off limits. Furthermore, spermatozoa from both the groups were subjected to label free liquid chromatography mass spectroscopy (LC-MS/MS) followed by bioinformatics analysis to elucidate the molecular mechanism(s) involved and the key proteins from the affected pathways were validated by western blot along with oxidative modification of proteins. Of the 16 standard PAH 13 were detected in the semen. Receiver Operator Character (ROC) Curve analysis (AUCROC) revealed the PAHs having most significant effect on fertility are of the following order Anthracene<benzo(a)pyrene<benzo[b]fluoranthene<Fluoranthene<benzo(a)anthracene<indol (123CD)pyrene<pyrene<naphthalene<dibenzo(AH)anthracene<fluorene<2bromonaphthalene <chrysene<benzo(GH1)perylene. Benzo[a] pyrene is invariably present in all infertile patients while naphthalene is present in both fertile and IMI group. Of the total 773 detected proteins (Control: 631 and PAH: 717); 71 were differentially expressed (13 underexpressed, 58 overexpressed) in IMI patients resulting in impaired mitochondrial dysfunction and oxidative phosphorylation, DNA damage, Aryl hydrocarbon receptor (AHR) signalling, xenobiotic metabolism and induction of NRF-2 mediated oxidative stress response (increased in 4-hydroxynonenal and nitrosylated protein adduct formation, and declined antioxidant defence). The increased GSH/GSSG ratio in patients may be an adaptive response to metabolize the xenobiotics via conjugation as evidenced by overexpression of AHR and Heat shock protein 90 beta (HSP90β) in patients. Seminal PAH concentrations, oxidative protein modification along with protein markers (e.g. AHR and HSP90β) may help in better prediction and management of IMI. Contribution of environment borne PAH in semen should not undermined in infertility evaluation.
Oscillatory dynamics underlying emotion-cognition integration: differential role of theta and alpha oscillations
Authors: Wang Zhihao , Goerlich Katharina S. , Chen Mai , Xu Pengfei , Luo Yuejia , Aleman André 
Published: March 2022

AbstractA fundamental aspect of human mental life is the seamless ability for integration of emotion and cognition. Despite progress regarding the spatial architecture of Emotion-Cognition Integration (ECI), the time course of ECI processes remains unclear. To examine the temporal organization of brain oscillations underpinning ECI, we simultaneously manipulated emotional valence of stimuli and cognitive task demand while recording electrophysiological responses of 61 participants. They were asked to complete tasks with low (body-part judgement) and high (laterality judgement) cognitive demand while viewing other people photographs that varied on dimensions of laterality (left or right), body-part (hand or foot), and emotional valence (pain or no pain). We found increased reaction times and error rates in pain versus no pain during laterality judgement relative to body-part judgement, suggesting reciprocal inhibition between emotion and cognition. EEG results showed that 1) emotion processing (valence) occurred first in the theta band from 144 to 372 ms; 2) cognitive processing (laterality) took place in the theta band from 332 to 608 ms; 3) emotional and cognitive processes were integrated in the alpha band from 268 ms and lasted to 800 ms. These findings reveal oscillatory dynamics of the processing and integration of emotion and cognition, providing further insights into the underlying neurophysiology. This may ultimately contribute to our understanding of ECI processing in psychopathology.
Kiawah and Seabrook islands are a critical site for therufaRed Knot (Calidris canutus rufa)
Authors: Pelton Mary Margaret , Padula Sara R. , Garcia-Walther Julian , Andrews Mark , Mercer Robert , Porter Ron , Sanders Felicia , Thibault Janet , Senner Nathan R. , Linscott Jennifer A. 
Published: March 2022

ABSTRACTTherufaRed Knot (Calidris canutus rufa) is a migratory shorebird that performs one of the longest known migrations of any bird species — from their breeding grounds in the Canadian Arctic to their nonbreeding grounds as far south as Tierra del Fuego — and has experienced a population decline of over 85% in recent decades. During migration, knots rest and refuel at stopover sites along the Atlantic Coast, including Kiawah and Seabrook islands in South Carolina. Here, we document the importance of Kiawah and Seabrook islands for knots by providing population and stopover estimates during their spring migration. We conducted on-the-ground surveys between 19 February - 20 May 2021 to record the occurrence of individually marked knots. In addition, we quantified the ratio of marked to unmarked knots and deployed geolocators on knots captured in the area. Using a superpopulation model, we estimated a minimum passage population of 17,247 knots (~41% of the totalrufaknot population) and an average stopover duration of 47 days. Our geolocator results also showed that knots using Kiawah and Seabrook islands can bypass Delaware Bay and fly directly to the Canadian Arctic. Finally, our geolocators, combined with resighting data from across the Atlantic Flyway, indicate that a large network of more than 70 coastal sites mostly concentrated along the coasts of Florida, Georgia, South Carolina, and North Carolina provide stopover and overwintering habitat for the knots we observed on Kiawah and Seabrook islands. These findings corroborate that Kiawah and Seabrook islands should be recognized as critical sites in the knot network and, therefore, a conservation priority. As a result, the threats facing the sites — such as prey management issues, anthropogenic disturbance, and sea level rise — require immediate attention.
Gene expression noise accelerates the evolution of a biological oscillator
Authors: Lin Yen Ting , Buchler Nicolas E. 
Published: March 2022

AbstractGene expression is a biochemical process, where stochastic binding and unbinding events naturally generate fluctuations and cell-to-cell variability in gene dynamics. These fluctuations typically have destructive consequences for proper biological dynamics and function (e.g., loss of timing and synchrony in biological oscillators). Here, we show that gene expression noise counter-intuitively accelerates the evolution of a biological oscillator and, thus, can impart a benefit to living organisms. We used computer simulations to evolve two mechanistic models of a biological oscillator at different levels of gene expression noise. We first show that gene expression noise induces oscillatory-like dynamics in regions of parameter space that cannot oscillate in the absence of noise. We then demonstrate that these noise-induced oscillations generate a fitness landscape whose gradient robustly and quickly guides evolution by mutation towards robust and self-sustaining oscillation. These results suggest that noise can help dynamical systems evolve or learn new behavior by revealing cryptic dynamic phenotypes outside the bifurcation point.Graphical Abstract
Enhancing the Fitness of Embryoid Bodies and Organoids by Chemical Cytoprotection
Authors: Ryu Seungmi , Weber Claire , Chu Pei-Hsuan , Tristan Carlos A. , Ernest Ben , Jovanovic Vukasin M. , Deng Tao , Slamecka Jaroslav , Hong Hyenjong , Braisted John , Hirst Marissa , Simeonov Anton , Voss Ty C. , Singeç Ilyas 
Published: March 2022

ABSTRACTEmbryoid bodies (EBs) and self-organizing organoids derived from human pluripotent stem cells (hPSCs) recapitulate tissue development in a dish and hold great promise for disease modeling and drug development. However, current protocols are hampered by cellular stress and apoptosis during cell aggregation, resulting in variability and impaired cell differentiation. Here, we demonstrate that EBs and various organoid models (e.g., brain, gut, and kidney) can be optimized by using the CEPT small molecule cocktail, a polypharmacology approach that ensures cytoprotection and cell survival. Application of CEPT (chroman 1, emricasan, polyamines, trans-ISRIB) for just 24 hours during cell aggregation has long-lasting consequences affecting morphogenesis, gene expression, and cellular differentiation. Various qualification methods confirmed that CEPT treatment consistently improved EB and organoid fitness as compared to the widely used ROCK inhibitor Y-27632. Collectively, we discovered that stress-free cell aggregation and superior cell survival in the presence of CEPT are critical quality control determinants that establish a robust foundation for bioengineering complex tissue and organ models.
BNIP3 upregulation characterizes cancer cell subpopulation with increased fitness and proliferation
Authors: Zhu Yanyan , Chen Bowang , Yan Junya , Zhao Wendi , Dou Pengli , Sun Na , Wang Yaokai , Huang Xiaoyun 
Published: March 2022

AbstractBNIP3 is a BH3 only protein with both pro-apoptotic and pro-survival roles depending on the cellular context. It remains unclear how BNIP3 RNA level dictates cell fate decisions of cancer cells. Here we undertook a quantitative analysis of BNIP3 expression and functions in single cell datasets of various epithelial malignancies. Our results demonstrated that BNIP3 upregulation characterizes cancer cell subpopulations with increased fitness and proliferation. We further validated the upregulation of BNIP3 in liver cancer organoids compared with 2D culture. Taken together, the combination of in silico perturbations using public single cell datasets and experimental cancer modeling using organoids ushered in a new approach to address cancer heterogeneity.
Mooney Face Image Processing in Deep Convolutional Neural Networks Compared to Humans
Authors: Zeman Astrid , Leers Tim , de Beeck Hans Op 
Published: March 2022

AbstractDeep Convolutional Neural Networks (CNNs) are criticised for their reliance on local shape features and texture rather than global shape. We test whether CNNs are able to process global shape information in the absence of local shape cues and texture by testing their performance on Mooney stimuli, which are face images thresholded to binary values. More specifically, we assess whether CNNs classify these abstract stimuli as face-like, and whether they exhibit the face inversion effect (FIE), where upright stimuli are classified positively at a higher rate compared to inverted. We tested two standard networks, one (CaffeNet) trained for general object recognition and another trained specifically for facial recognition (DeepFace). We found that both networks perform perceptual completion and exhibit the FIE, which is present over all levels of specificity. By matching the false positive rate of CNNs to humans, we found that both networks performed closer to the human average (85.73% for upright, 57.25% for inverted) for both conditions (61.31% and 62.70% for upright, 48.61% and 42.26% for inverted, for CaffeNet and DeepFace respectively). Rank order correlation between CNNs and humans across individual stimuli shows a significant correlation in upright and inverted conditions, indicating a relationship in image difficulty between observers and the model. We conclude that in spite of the texture and local shape bias of CNNs, which makes their performance distinct from humans, they are still able to process object images holistically.
Patient-Level Clinical Expertise Enhances Prostate Cancer Recurrence Predictions with Machine Learning
Authors: Vallon Jacqueline Jil , Panjwani Neil , Ling Xi , Vij Sushmita , Srinivas Sandy , Leppert John , Bayati Mohsen , Buyyounouski Mark K. 
Published: March 2022

AbstractWith rising access to electronic health record data, application of artificial intelligence to create clinical risk prediction models has grown. A key component in designing these models is feature generation. Methods used to generate features differ in the degree of clinical expertise they deploy (from minimal to population-level to patient-level), and subsequently the extent to which they can extract reliable signals and be automated. In this work, we develop a new process that defines how to systematically implementpatient-levelclinician feature generation (CFG), which leverages clinical expertise to define concepts relevant to the outcome variable, identify each concept’s associated features, and finally extract most features on a per-patient level by manual chart review. We subsequently apply this method to identifying and extracting patient-level features predictive of cancer recurrence from progress notes for a cohort of prostate cancer patients. We evaluate the performance of the CFG process against an automated feature generation (AFG) process via natural language processing techniques. The machine learning outcome prediction model leveraging the CFG process has a mean AUC-ROC of 0.80, in comparison to the AFG model that has a mean AUC-ROC of 0.74. This relationship remains qualitatively unchanged throughout extensive sensitivity analyses. Our analyses illustrate the value of in-depth specialist reasoning in generating features from progress notes and provide a proof of concept that there is a need for new research on efficient integration of in-depth clinical expertise into feature generation for clinical risk prediction.
Normative cognitive scores in western India, stratified by age, rurality, cognitive domains, and psychiatric comorbidity
Authors: Sundar Uma , Mukhopadhyay Amita , Sundar Suresh , Shah Nilesh 
Published: March 2022

AbstractBackground and objectivesIndian ethnic and educational diversities necessitate obtaining normative cognitive data in different populations. We aimed to evaluate cognitive scores using a Marathi translation of the Kolkata Cognitive Battery (KCB), and to study the association of KCB components with depression and socio-demographic variables.MethodologyWe studied 2651 individuals aged ≥40 years, without pre-existing neuropsychiatric conditions, from urban (Mumbai) and rural districts of Maharashtra. For each component of KCB, the lowest 10th percentile score was used to define cognitive impairment.ResultsWe studied 1435 (54%) rural and 1216 (46%) urban residents equally divided by gender (1316 women, 1335 men), average age 54 years. KCB scores were significantly lower with female sex, older age, illiteracy and depression. The largest effect sizes attributable to these factors were in the domains of calculation (gender), visuo-constructional ability (VCA; rurality) and verbal fluency (VF; depression). Scores remained significantly lower in rural residents after controlling for age, sex and education, particularly for VCA, immediate recall and calculation.ConclusionThis Marathi KCB having been validated on large urban as well as rural samples, may be used to study cognition in Marathi speaking populations with appropriate cut-offs tailored to the degree of urbanization of the population.
Genetically predicted on-statin LDL response is associated with higher intracerebral hemorrhage risk
Authors: Mayerhofer Ernst , Malik Rainer , Parodi Livia , Burgess Stephen , Harloff Andreas , Dichgans Martin , Rosand Jonathan , Anderson Christopher D , Georgakis Marios K 
Published: March 2022

AbstractStatins lower low-density lipoprotein (LDL) cholesterol and are widely used for the prevention of atherosclerotic cardiovascular disease. Whether statin-induced LDL reduction increases risk of intracerebral hemorrhage (ICH) has been debated for almost two decades. Here, we explored whether genetically predicted on-statin LDL response is associated with ICH risk using Mendelian Randomization. Utilizing genomic data from randomized trials, we derived a polygenic score from 35 single nucleotide polymorphisms (SNP) of on-statin LDL response and tested it in the population-based UK-Biobank (UKB). We extracted statin drug and dose information from primary care data on a subset of 225,195 UKB participants covering a period of 29 years. We validated the effects of the genetic score on longitudinal LDL measurements with generalized mixed models and explored associations with incident ICH using Cox regression analysis. Statins were prescribed at least once to 75,973 (31%) of the study participants (mean 57 years, 55% females). Among statin users, mean LDL decreased by 3.45 mg/dl per year (95% CI: [-3.47, -3.42]) over follow-up. A higher genetic score of statin response (one SD increment) was associated with significant additional reductions in LDL levels (−0.05 mg/dl per year, [-0.07, -0.02]), showed concordant lipidomic effects on other lipid traits as statin use, and was associated with a lower risk for incident myocardial infarction (HR per SD increment 0.98 95% CI [0.96, 0.99]) and peripheral artery disease (HR per SD increment 0.92 95% CI [0.86, 0.98]). Over a 11-year follow-up period, a higher genetically predicted statin response among statin users was associated with higher ICH risk in a model adjusting for statin dose (HR per SD increment 1.15, 95% CI [1.04, 1.27]). On the contrary, there was no association with ICH risk among statin non-users (p=0.89). These results provide further support for the hypothesis that statin-induced LDL reduction may be causally associated with ICH risk. While the net benefit of statins for preventing vascular disease is well-established, these results provide insights about the personalized response to statin intake and the role of pharmacologic LDL-lowering in the pathogenesis of ICH.
Research on the Emotions of Uninfected People during the COVID-19 Epidemic in China
Authors: Chen Gang , Yue Juan-Juan 
Published: March 2022

AbstractBackgroundThe negative emotions induced by the ongoing coronavirus disease 2019 (COVID-19) epidemic are affecting people’s health. In order to identify emotional problems and promote early intervention to reduce the risk of disease, we studied the emotional states of Chinese people during the epidemic.MethodWe adopted the Automated Neuropsychological Assessment Metrics mood scale and prepared an online questionnaire. Then, we conducted an exploratory factor analysis of the effective responses of 567 participants from 31 provinces and cities in China. Finally, we analyzed the characteristics of the distribution of different types of emotions and compared them via several statistical methods.ResultsThe original scale was modified to have six dimensions that yielded reliable internal consistency values ranging from 0.898 to 0.965 and explained 74.96% of the total variance. We found that a total of 33.9% of respondents felt negative emotions more strongly, were less happy and had less energy than other respondents (p<0.001). People with these traits had relatively serious emotional problems and were typically over 60 years old, doctoral degree holders, enterprise personnel and residents in an outbreak area.ConclusionThirty-three percent of people without COVID-19 had emotional problems. Psychotherapy should be provided as early as possible for people with emotional problems caused by the epidemic, and the modified scale could be used to survey the public’s mood during public health events to detect problems and facilitate early intervention.
A comparison of paediatric hypertension clinical practice guidelines and their ability to predict adult hypertension in an African birth cohort
Authors: Craig Ashleigh , Ware Lisa J , Mapanga Witness , Norris Shane A 
Published: March 2022

AbstractIt remains unclear which paediatric hypertension clinical practice guideline (CPG) should be applied in an African population. We therefore aimed to compare three commonly used CPG (2017 AAP, 2016 ESH and 2004 Fourth Report) developed in high-income countries for use in South African children at four paediatric ages (children: 5yrs and 8yrs; adolescents: 13yrs and 17yrs) to determine which best predicts elevated blood pressure (EBP) in young adulthood (22yrs and 28yrs). Moreover, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for each specific paediatric CPG was calculated. The 2017 AAP definition identified more children and adolescents with hypertension when compared to the 2004 Fourth Report and 2016 ESH guidelines. In computed hazards ratios, from ages 8yrs to 17yrs, all three paediatric CPG significantly predicted the risk of EBP in young adulthood (p≤0.008). However, sensitivity to predict EBP at age 22yrs for all CPG was generally low (17.0% - 33.0%) with higher specificity (87.4% - 93.1%). Sensitivity increased at age 28yrs (51.4.0% - 70.1%), while specificity decreased (52.8% - 65.1%). Both PPV and NPV at both adult age points varied widely (17.9% - 79.9% and 29.3% - 92.5% respectively). The performance of these paediatric CPG in terms of AUC were not optimal at both adult age points, however, the AAP definition at 17yrs met an acceptable level of performance (AUC= 0.71). Our results highlight the need for more research to examine if an African-specific CPG would better identify high-risk children to minimise their trajectory towards adult hypertension.
Medication Against Conflict
Authors: Berlanda Andrea , Cervellati Matteo , Esposito Elena , Rohner Dominic , Sunde Uwe 
Published: March 2022

AbstractThe consequences of successful public health interventions for social violence and conflict are largely unknown. This paper closes this gap by evaluating the effect of a major health intervention – the successful expansion of anti-retroviral therapy (ART) to combat the HIV/AIDS pandemic – in Africa. To identify the effect, we combine exogenous variation in the scope for treatment and global variation in drug prices. We find that the ART expansion significantly reduced the number of violent events in African countries and sub-national regions. The effect pertains to social violence and unrest, not civil war. The evidence also shows that the effect is not explained by general improvements in economic prosperity, but related to health improvements, greater approval of government policy, and increased trust in political institutions. Results of a counterfactual simulation reveal the largest potential gains in countries with intermediate HIV prevalence where disease control has been given relatively low priority.JEL-classification: C36, D47, I15, O10