bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decoding and modifying dynamic attentional bias in gaming disorder
Authors: Oka Taiki , Kubo Takatomi , Kobayashi Nao , Murakami Misa , Chiba Toshinori , Cortese Aurelio 
Published: October 2024

With the spread of smartphones and computer games, concerns have escalated regarding the rising prevalence of gaming disorder. Patients often display attentional biases, unconsciously turning their attention towards gaming-related stimuli. However, attempts to discover and ameliorate these attentional deficits have yielded inconsistent outcomes, potentially due to the dynamic nature of attentional bias. This study investigated neural mechanisms underlying attentional bias state by combining neuroimaging (functional magnetic resonance imaging -fMRI) with an approach-avoidance task tailored to an individual’s gaming preference. We conducted a multivariate pattern analysis of endogenous brain activity in 21 participants with probable gaming disorder. Our analyses revealed that activity patterns in the insula tracked temporal attentional bias states specific to gaming stimuli. A broad network of frontal and parietal regions instead appeared to predict a general temporal attentional bias state. Finally, we conducted a proof-of-concept study for ‘just-in-time’ attentional bias training through fMRI-decoded neurofeedback of insula activity patterns, named decoded attentional bias training (DecABT). Our preliminary results suggest that DecABT may help to decrease the attractiveness of gaming stimuli via a insula- and precuneus-based neural mechanism. This work provides new evidence for the insula as an endogenous regulator of attentional bias states in gaming disorder and a starting point to develop novel, individualized therapeutic approaches to treat addiction.This article is part of the theme issue ‘Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation’.
Amygdala self-neuromodulation capacity as a window for process-related network recruitment
Authors: Gurevitch Guy , Lubianiker Nitzan , Markovits Taly , Or-Borichev Ayelet , Sharon Haggai , Fine Naomi B. , Fruchtman-Steinbok Tom , Keynan Jacob N. , Shahar Moni , Friedman Alon , Singer Neomi , Hendler Talma 
Published: October 2024

Neurofeedback (NF) has emerged as a promising avenue for demonstrating process-related neuroplasticity, enabling self-regulation of brain function. NF targeting the amygdala has drawn attention to therapeutic potential in psychiatry, by potentially harnessing emotion-regulation processes. However, not all individuals respond equally to NF training, possibly owing to varying self-regulation abilities. This underscores the importance of understanding the mechanisms behind successful neuromodulation (i.e. capacity). This study aimed to investigate the establishment and neural correlates of neuromodulation capacity using data from repeated sessions of amygdala electrical fingerprint (Amyg-EFP)-NF and post-training functional magnetic resonance imaging (fMRI)-NF sessions. Results from 97 participants (healthy controls and post-traumatic stress disorder and fibromyalgia patients) revealed increased Amyg-EFP neuromodulation capacity over training, associated with post-training amygdala-fMRI modulation capacity and improvements in alexithymia. Individual differenaces in this capacity were associated with pre-training amygdala reactivity and initial neuromodulation success. Additionally, amygdala downregulation during fMRI-NF co-modulated with other regions such as the posterior insula and parahippocampal gyrus. This combined modulation better explained EFP-modulation capacity and improvement in alexithymia than the amygdala modulation alone, suggesting the relevance of this broader network to gained capacity. These findings support a network-based approach for NF and highlight the need to consider individual differences in brain function and modulation capacity to optimize NF interventions.
This article is part of the theme issue ‘Neurofeedback: new territories and neurocognitive mechanisms of endogenous neuromodulation’.
Effects of METTL3-METTL14 on primary microRNA processing by Drosha-DGCR8
Authors: Khadgi Brijesh , Nam Yunsun 
Published: October 2024

AbstractMicroRNAs modulate most protein-coding genes, and many are regulated during maturation. Chemical modifications of primary transcripts containing microRNAs have been implicated in altering Microprocessor processing efficiency, a key initiating endonucleolytic step performed by Drosha and DGCR8. METTL3-METTL14 produces N6-methyladenosine which is the most common methylation for mRNAs. Genetic experiments suggested that METTL3-METTL14 promotes primary microRNA processing by Microprocessor, but the molecular mechanism still needs to be elucidated. We tested the hypothesis that METTL3-METTL14 or m6A may directly impact Drosha or DGCR8 function during primary microRNA processing. After reconstituting the methyltransferase and processing activities, we show that the presence of METTL3-METTL14 complexes does not affect the processing efficiency of Drosha-DGCR8. We also established a method to prepare m6A-modified primary microRNAs and used them to show that the processing of the transcripts with m6A is similar to those without any modification. Recombinant METTL3-METTL14 and DGCR8 do not form stable complexes, challenging the previous model that depends on enhanced DGCR8 recruitment. Therefore, METTL3-METTL14 or m6A modification does not generally promote Microprocessor-mediated microRNA processing, although they may impact certain cases.
Polygenic modifiers of expressivity in telomere biology disorders
Authors: Poeschla Michael , Arora Uma P. , Walne Amanda , McReynolds Lisa J. , Niewisch Marena R. , Giri Neelam , Zeigler Logan , Gusev Alexander , Machiela Mitchell J. , Tummala Hemanth , Savage Sharon A. , Sankaran Vijay G. 
Published: October 2024

AbstractVariable expressivity, where individuals carrying identical genetic variants display diverse phenotypes, presents an important challenge in clinical genetics. This is exemplified by the telomere biology disorders (TBDs), which exhibit tremendous clinical heterogeneity despite their presumed monogenic nature, even among individuals harboring the same pathogenic variant. Here, we studied cohorts of patients with TBDs and population biobanks to demonstrate that common genome-wide polymorphisms associated with variation in telomere length in the general population combine with large-effect causal variants to significantly impact TBD expressivity. We go on to show that polygenic variation can contribute to expressivity within a single family with a shared large-effect causal variant, and that common and rare variation converge on a shared set of genes implicated in telomere maintenance. By elucidating the role of common genetic variation in rare disease expressivity in TBDs, these results provide a framework for understanding phenotypic variability in other presumed monogenic disorders.
Multi-ancestry proteome-phenome-wide Mendelian randomization offers a comprehensive protein-disease atlas and potential therapeutic targets
Authors: Su Chen-Yang , van der Graaf Adriaan , Zhang Wenmin , Jang Dong-Keun , Selber-Hnatiw Susannah , Yang Ta-Yu , Butler-Laporte Guillaume , Liang Kevin Y. H. , Matsuda Fumihiko , Costanzo Maria C. , Burtt Noel P. , Flannick Jason , Zhou Sirui , Mooser Vincent , Lu Tianyuan , Yoshiji Satoshi 
Published: October 2024

AbstractCirculating proteins influence disease risk and are valuable drug targets. To enhance the discovery of protein-phenotype associations and identify potential therapeutic targets across diverse populations, we conducted proteome-phenome-wide Mendelian randomization in three ancestries, followed by comprehensive sensitivity analyses. We tested the potential causal effects of up to 2,265 unique proteins on a curated list of 355 distinct phenotypes, assessing 726,035 protein-phenotype pairs in European, 33,078 in African, and 115,352 in East Asian ancestries. Notably, 119 proteins were instrumentable only in African ancestry and 17 proteins only in East Asian ancestry due to allele frequency differences that are common in these ancestries but rare in European ancestry. We identified 3,949, 56, and 325 unique protein-phenotype pairs in European, African, and East Asian ancestries, respectively, and assessed their druggability using multiple databases. We highlighted the causal role of IL1RL1 in inflammatory bowel diseases, supported by multiple orthogonal lines of evidence. Taken together, this study underscores the importance of multi-ancestry inclusion and offers a comprehensive atlas of protein-phenotype associations across three ancestries, enhancing our understanding of proteins involved in disease etiology and potential therapeutic targets. Results are available at the Common Metabolic Diseases Knowledge Portal (https://broad.io/protein_mr_atlas).
OPTICAL BLUR AFFECTS DIFFERENTLY ON AND OFF VISUAL PATHWAYS
Authors: Pons Carmen , Mazade Reece , Jin Jianzhong , Dul Mitchell , Alonso Jose-Manuel 
Published: October 2024

SUMMARYThe human eye has a crystalline lens that focuses retinal images at the point of fixation. Outside this fixation region, images are distorted by optical blur, which increases light scatter and reduces the spatial resolution and contrast processed by neuronal pathways. The spectacle lenses that humans use for optical correction also minify or magnify the images, affecting neuronal surround suppression in visual processing. Because light and dark stimuli are processed with ON and OFF pathways that have different spatial resolution, contrast sensitivity and surround suppression, optical blur and image magnification should affect differently the two pathways and the perception of lights and darks. Our results provide support for this prediction in cats and humans. We demonstrate that optical blur expands ON receptive fields while shrinking OFF receptive fields, as expected from the expansion of light stimuli and shrinkage of dark stimuli with light scatter. Spectacle-induced image magnification also shrinks OFF more than ON receptive fields, as expected from the stronger surround suppression in OFF than ON pathways. Optical blur also decreases the population response of OFF more than ON pathways, consistent with the different effects of light scatter on dark and light stimuli and the ON-OFF pathway differences in contrast sensitivity. Based on these results, we conclude that optical blur and image magnification reduce the receptive field sizes and cortical responses of OFF more than ON pathways, making the ON-OFF response balance a reliable signal to optimize the size and quality of the retinal image.HIGHLIGHTSOptical blur affects ON and OFF pathways differently.Blur expands ON but shrinks OFF receptive fields, weakening OFF more than ON signals.Magnification from positive blur reduces OFF more than ON signal strength and latency.ON-OFF response balance can signal retinal image quality and guide eye growth.IN BRIEFPons et al. demonstrate that optical blur affects differently the receptive field properties and responses from ON and OFF visual pathways, revealing a new relation between ON/OFF pathway balance and blurred visual perception. The results highlight a new role of ON and OFF pathways in optimizing retinal image quality that can have implications for the regulation of eye growth.GRAPHICAL ABSTRACT
Replicating clinical placebo effects in computational trials: Bridging the gap between in silico and clinical studies
Authors: Dominguez-Gomez Paula , Butakoff Constantine , Rast Georg , Darpo Borje , Vazquez Mariano , Aguado-Sierra Jazmin 
Published: October 2024

AbstractThis study replicates human cardiac safety clinical trials using computational models, which include diurnal hormonal placebo effects, aiming to create fast and efficient drug screening tools to assess QT interval prolongation preclinically. A virtual cardiac population that simulates sex-specific electrophysiological variability influenced by diurnal hormonal cycles was created to closely mirror human physiology. The goal is to assess the impact of these hormone dynamics on placebo-induced responses and evaluate the virtual population’s accuracy in reflecting clinical trial outcomes.The study showed that the virtual population model successfully replicated about 50% of the observed QT variability seen in placebo groups. The computational framework facilitated direct comparison with human clinical trials, achieving critical concentrations, i.e., concentrations that cause a mean QTc effect of 10 ms, within a 0.6-fold range of clinical results. Additionally, the exposure-response slopes exhibited relative errors averaging 43%, which translates into mean absolute errors of 6-7 ms in comparison to clinical data. These results highlight its potential to reproduce human physiology and provide results consistent with real-world human clinical trials. Additionally, a comparison with a previously published statistical placebo model further supports this approach. By approximating the diurnal hormonal variations, as a component of the mechanistic basis of placebo, this method offers a robust decision-making tool for early-stage drug safety assessment.HighlightsDiurnal hormonal fluctuations significantly contribute to intersubject variability observed in placebo responses.Modeling conservative diurnal hormonal variations can reproduce approximately 50% of QT interval prolongation variability within placebo groups.Comprehensive human clinical trials for cardiac safety drug testing, including placebo effects and placebo-corrected QT interval prolongation, can be accurately replicated through virtual human computational models showing mean absolute errors of 6-7 ms.Graphical Abstract
Multimorbidity Patterns of Chronic Diseases Among Adults in Rural North China
Authors: Tang Shuai , Li Yanxing , Niu Meili , Qi Zijing , Hao Tianyou , Yang Hongmei , Tian Maoyi , Zhang Xinyi , Feng Xiangxian , Li Zhifang 
Published: October 2024

AbstractBackgroundThe incidence of chronic diseases is increasing, especially in rural areas, where younger patients often exhibit multimorbidity. Understanding multimorbidity in rural adults can guide the development of targeted management strategies for chronic diseases.MethodsThis cross-sectional study was conducted in rural North China using whole cluster stratified random sampling to select two counties in Shanxi Province. A total of 2,208 participants aged 30 years or older from 80 villages were enrolled, stratified by gender and age. Data collection involved questionnaires on socio-demographic characteristics, lifestyle, and disease history, along with physical measurements such as height, weight, and waist circumference.ResultsAmong the 2,208 participants, 58.11% were aged 30-59 years, and 52.17% were female. The prevalence of chronic diseases was 66.53%, with a multimorbidity rate of 32.47%. The most common conditions were hypertension (43.21%), chronic digestive diseases (11.82%), and stroke (10.19%). Multimorbidity was more prevalent in those aged ≥60 years compared to the 30-59 age group (47.68% vs. 21.51%, P<0.05), with no significant gender differences. Hypertension was present in 78.52% of disease patterns, with common dyads being hypertension & stroke (7.47%), hypertension & heart disease (6.25%), and hypertension & diabetes mellitus (6.11%). In the 30-59 age group, hypertension & chronic digestive disease (3.82%) were most prevalent, while for those aged ≥60 years and males, hypertension & stroke were most common (12.65% and 9.47%, respectively). Among females, the most frequent dyad was hypertension & arthritis (8.16%).ConclusionChronic diseases and multimorbidity are prevalent in rural North China, primarily driven by hypertension. Multimorbidity patterns differ by age and gender, indicating the need for targeted prevention and treatment strategies.
Application of decision-analytic models to inform integrated care interventions for cardiometabolic multimorbidity: A systematic review
Authors: Wambiya Elvis O. A. , Gillespie Duncan , Akparibo Robert , Oguta James O. , Akoth Catherine , Otieno Peter , Dodd Peter J. 
Published: October 2024

AbstractIntroductionIntegrated care is increasingly being adopted to address the complex needs of patients with cardiometabolic multimorbidity. However, it is unclear how to cost-effectively configure health service pathways for these patients. This study aimed to review and appraise decision analytic models (DAMs) used in economic evaluations of integrated care interventions for patients with cardiometabolic multimorbidity.MethodsWe conducted a systematic search for peer-reviewed articles in eight electronic databases, published in English language until December 2023. Any study worldwide that used a decision-analytic model to conduct an economic evaluation of an integrated care model for patients with cardiometabolic multimorbidity was included. We summarised characteristics of the DAMs, integrated care models evaluated, diseases constituting multimorbidity, and critically appraised the quality of reporting of the economic evaluations using Philips (2006) checklist.ResultsOut of 16 model-based assessments of the differences between alternative integrated care pathways, most studies (n=13, 81%) were cost utility analyses, focused on care for patients with hypertension and/or diabetes concordant multimorbidity (n=11, 69%). Most studies were conducted in high-income countries (n = 11, 69%). More than half (n = 10, 63%) of the studies used simulated Markov models, while only three studies used individual sampling (microsimulation) models. Few studies were explicit about their data validation approaches against local data, quality of data incorporated in the models, and internal and external consistency.ConclusionDecision-analytic models investigating integrated care pathways for cardiometabolic multimorbidity should employ microsimulation to describe and incorporate repeated patient interactions with health care and multimorbidity outcomes in the economic evaluations. Consideration of uncertainty in data sources and model structure is also needed to provide robust conclusions. The study also highlighted the need for more economic evaluations using DAMs in low- and middle-income countries to evaluate integrated care models in the context of cardiometabolic multimorbidity.
Machine learning analysis of the UNOS database fails to predict lung transplant outcomes
Authors: Luo Lucy , Możejko Marcin , Markov Nikolay S. , Peltekian Alec , Moshin Suror , Carns Mary , Cooper Phillip , Lysne Jeffrey , Joudi Anthony , Betensley Alan , Bemiss Bradford C. , Myers Catherine , Bharat Ankit , Tomic Rade , Arunachalam Ambalavanan , Szczurek Ewa , Budinger GR Scott , Misharin Alexander V. , Subramani Mrinalini Venkata 
Published: October 2024

AbstractBackgroundLung transplantation is the only life-saving therapy for end-stage lung disease. However, lung transplantation has the worst survival among all solid organ transplants.1We applied machine learning to a large standardized electronic health record (EHR) dataset from the United Network for Organ Sharing (UNOS) to test whether pre- transplant and peri-transplant donor and recipient features can predict one-, three- and five-year survival, or favorable long-term outcomes in lung transplant.MethodsWe used data from 43,869 first time lung transplant recipients >18 years old from 1987 to November 2022 for whom one-, three-, and five-year survival outcomes were available. We applied XGBoost or a tabular BERT model called EHRFormer to the UNOS EHR dataset.ResultsUsing pre-transplant features XGBoost predicted one year mortality with a test AUC = 0.6 [0.57, 0.64] 95% CI. Addition of peri-transplant features only modestly improved AUC for one-year mortality prediction (test AUC = 0.63 [0.60, 0.67] 95% CI and 0.64 [0.63, 0.66] 95% CI for XGBoost and EHRFormer, respectively). Top predictive features of one year mortality using peri-transplant features from each model were length of index stay, transplant type, recipient age, ventilation status during the index stay, and creatinine at the time of transplant. Both XGBoost and EHRFormer performed better when predicting lung function at one-year post-transplant (XGBoost test AUC = 0.74; EHRFormer test AUC = 0.76). Both models identified and used features previously associated with transplant outcomes to inform predictions.ConclusionsDespite machine learning approaches identifying known risk factors for transplant outcomes, EHR data collected by UNOS poorly predict one-, three-, and five-year mortality outcomes of lung transplantation. These results suggest caution when using pre-transplant EHR features to predict lung transplant outcomes.
Hybrid incompatibility emerges at the one-cell stage in interspeciesCaenorhabditisembryos
Authors: Bloom Jessica , Green Rebecca , Desai Arshad , Oegema Karen , Rifkin Scott A. 
Published: October 2024

SUMMARYIntrinsic reproductive isolation occurs when genetic differences between populations disrupt the development of hybrid organisms, preventing gene flow and enforcing speciation.1–4While prior studies have examined the genetic origins of hybrid incompatibility,5–18the effects of incompatible factors on development remain poorly understood. Here, we investigate the mechanistic basis of hybrid incompatibility inCaenorhabditisnematodes by capitalizing on the ability ofC. brennerifemales to produce embryos after mating with males from several other species. Contrary to expectations, hybrid incompatibility was evident immediately after fertilization, suggesting that post-fertilization barriers to hybridization originate from physical incompatibility between sperm and oocyte-derived factors rather than from zygotic transcription, which starts after the 4-cell stage.19–22Sperm deliver chromatin, which expands to form a pronucleus, and a pair of centrioles, which form centrosomes that attach to the sperm-derived pronucleus and signal to establish the embryo’s anterior-posterior axis.23,24InC. brennerioocytes fertilized withC. eleganssperm, sperm pronuclear expansion was compromised, frequent centrosome detachment was observed, and cortical polarity was disrupted. Live imaging revealed that defective polar body extrusion contributes to defects in mitotic spindle morphology.C. brennerioocytes fertilized withC. remaneiorC. sp. 48sperm showed similar defects, and their severity and frequency increased with phylogenetic distance. Defective expansion of the sperm-derived pronucleus and unreliable polar body extrusion immediately after fertilization generally underlie the inviability of hybrid embryos in this clade. These results indicate that physical mismatches between sperm and oocyte-derived structures may be a primary mechanism of hybrid incompatibility.