bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial DNA and the STING pathway are required for hepatic stellate cell activation
Authors: Arumugam Suyavaran , Li Binghua , Boodapati Sri Lakshmi Tejaswi , Nathanson Michael H. , Sun Beicheng , Ouyang Xinshou , Mehal Wajahat Z. 
Published: April 2023

Background and Aims:
TGF-β induces multiple structural and functional changes in quiescent HSCs, including an increase in proliferation, mitochondrial mass, and matrix deposition. HSC transdifferentiation requires significant bioenergetic capacity, and it is not known how TGF-β–mediated transcriptional upregulation is coordinated with the bioenergetic capacity of HSCs.

Approach and Results:
Mitochondria are key bioenergetic organelles, and here, we report that TGF-β induces release of mitochondrial DNA (mtDNA) from healthy HSCs through voltage-dependent anion channels (VDACs), with the formation of an mtDNA-CAP on the external mitochondrial membrane. This stimulates organization of cytosolic cyclic GMP-AMP synthase (cGAS) onto the mtDNA-CAP and subsequent activation of the cGAS-STING-IRF3 pathway. TGF-β is unable to induce conversion of HSCs from a quiescent to a transdifferentiated phenotype in the absence of mtDNA, VDAC, or stimulator of interferon genes (STING). Transdifferentiation by TGF-β is blocked by a STING inhibitor, which also reduces liver fibrosis prophylactically and therapeutically.

Conclusions:
We have identified a pathway that requires the presence of functional mitochondria for TGF-β to mediate HSC transcriptional regulation and transdifferentiation and therefore provides a key link between bioenergetic capacity of HSCs and signals for transcriptional upregulation of genes of anabolic pathways.
Increasing Access to Medical Forensic Care for the Pediatric Patient
Authors: Lechner Megan , Hagedorn Sarah 
Published: April 2023

ABSTRACT
Child sexual abuse is a major public health problem. About one in every four girls and one in every 13 boys in the United States experience sexual abuse. In order to best serve these patients and families, the forensic nurse examiner team from a large urban Level 1 trauma center partnered with the local child advocacy center to provide ready access to educated, competent pediatric examiners who provide developmentally appropriate medical forensic care in a child-friendly environment. Consistent with national best practice standards, this occurs as part of a coordinated, colocated, highly functional multidisciplinary team. These services are provided free of charge and regardless of timeline from abuse. This partnership removes several key barriers to this care, including difficulty coordinating with multiple organizations, cost, lack of knowledge regarding available resources, and decreased ability to provide medical forensic care to nonacute patients.
Environmental sustainability in otolaryngologic surgery
Authors: Dilger Amanda E. , Bergmark Regan W. 
Published: April 2023

Purpose of review
Climate change is an urgent public health crisis that significantly impacts disease development, health outcomes, and access to care. The major approaches to climate change are mitigation and adaptation. The purpose of this review is to discuss the effects of climate change on health and health disparities, review the carbon footprint of surgical care and discuss strategies for surgeons to reduce emissions and advocate for sustainability.

Recent findings
Recent studies increasingly demonstrate the direct and indirect health effects of climate change, including the relationship between climate and otolaryngologic disease. Within the domain of otolaryngology, we summarize findings related to climate change and health and healthcare delivery; health disparities; healthcare-associated emissions; and the role of otolaryngologists in mitigating and adapting to the climate crisis. There are many recent studies that identify impactful sustainability opportunities and initiatives for healthcare providers. Climate solutions may also reduce cost and have potential clinical benefits.

Summary
Climate change and air pollution directly impact disease burden in otolaryngology patients and are underrecognized social determinants of health. Surgeons can lead on climate change by implementing sustainability initiatives in the operating room and engaging in research and advocacy.
Barriers to head and neck cancer care in high-income and low- and middle-income countries: a scoping review
Authors: Sprow Holly , Heer Baveena , Nuss Sarah , Jashek-Ahmed Farizeh , Wiedermann Joshua , Seguya Amina 
Published: April 2023

Purpose of review
Identify patient-perceived barriers to head and neck cancer care and compare differences in barriers by country income status.

Recent Findings
Of the 37 articles, 51% (n = 19) were from low- and middle-income countries (LMICs), while 49% (n = 18) were from high-income countries. Of the papers from high-income countries, unspecified head and neck cancer (HNC) subtype (67%, n = 12) were the most common cancer type, while upper aerodigestive tract mucosal malignancies (58%, n = 11) were more common in LMICs (P = 0.02). Based on World Health Organization barriers, level of education (P =  < 0.01) and alternative medicine use (P = 0.04) were greater barriers in LMICs compared to high-income countries. At least 50% of articles listed barriers at all three ‘Three Delays’ timepoints. There were no significant differences by country income status for the ‘Three Delays’ timepoints of deciding to seek care (P = 0.23), reaching the healthcare facility (P = 0.75), or receiving care (P = 1.00).

Summary
Patients face barriers to care for head and neck cancer regardless of country income status. There is overlap in several barriers and a need for systemic improvement in access. The differences in education and alternative medicine may guide region-specific interventions to improve the provision of head and neck services.
Retrograde intrarenal surgery for stones associated with renal anomalies: caliceal diverticulum, horseshoe kidney, medullary sponge kidney, megacalycosis, pelvic kidney, uretero-pelvic junction obstruction
Authors: Corrales Mariela , Sierra Alba 
Published: April 2023

Purpose of review
Nowadays, due to the increase of imaging diagnosis, we identify easily renal anomalies, and we can choose between a wide range of armamentarium to treat symptomatic stones in those challenging cases. However, there is a lack of evidence and consensus on its use. The aim of this narrative review is to collect all the available data about safety and efficacity of retrograde intrarenal surgery (RIRS) in the treatment of kidney stones associated to a renal anomaly.

Recent findings
Renal anomalies are uncommon findings and even more if it has to be associated with renal stones. After a literature review of the past 2 years, there are a small number of studies that compare the outcomes in patients who have been treated with minimally invasive modalities and they are mainly focus on RIRS.

Summary
It is of extreme importance to know the advances on the stone treatment in anomalous kidneys. With the development of new laser technologies, RIRS is becoming a more interesting technique with high success rate and safety. Further studies are needed to make an accurate statement about the adequate surgical technique for each renal anomaly and also, clinical trials using new laser technologies.
Spirituality/Religion and Self-Harm Among Patients With Alcohol/Substance Use Versus Other Disorders
Authors: Kaufman Caroline C. , Pirutinsky Steven , Rosmarin David H. 
Published: April 2023

Abstract
Spirituality/religion (S/R) is clinically relevant to recovery from alcohol use disorders (AUDs)/substance use disorders (SUDs) and also associated with less self-injury; however, the interplay of these factors has not been adequately evaluated. Participants (n = 1443) were culled from a larger study among psychiatric patients. We assessed for S/R using self-report measures, and medical records were reviewed for demographics, clinical diagnoses, psychiatric medications, and self-harm engagement. Self-harm engagement was significantly higher among patients without AUD/SUD. S/R distress was higher among participants with AUD/SUD, but S/R community activity and importance of religion were lower. Interest in discussing S/R in treatment did not significantly differ across patients. Religious affiliation, importance of religion, and belief in God were associated with less self-harm, but effects were not moderated by presence of AUD/SUD. S/R factors are associated with lower self-harm, irrespective of the presence or absence of AUD/SUD. In contrast with clinical lore, S/R may be equally salient to psychiatric patients with AUD/SUD versus other disorders.
Enabled primarily controls filopodial morphology, not actin organization, in the TSM1 growth cone inDrosophila
Authors: Fang Hsiao Yu , Forghani Rameen , Clarke Akanni , McQueen Philip G. , Chandrasekaran Aravind , O’Neill Kate M. , Losert Wolfgang , Papoian Garegin A. , Giniger Edward 
Published: April 2023

AbstractEna/VASP proteins are processive actin polymerases that are required throughout animal phylogeny for many morphogenetic processes, including axon growth and guidance. Here we use live imaging of morphology and actin organization in the TSM1 axon of the Drosophila wing to dissect the mechanism of Ena action. We find that altering Ena activity has a substantial impact on filopodial morphology in this growth cone, but exerts only modest effects on actin organization. This is in contrast to the main regulator of Ena, Abl tyrosine kinase, which has profound effects on actin and only mild effects on TSM1 growth cone morphology. These data suggest that the primary role of Ena in this axon may be to link actin to morphogenetic processes of the plasma membrane, rather than regulating actin organization itself. These data also suggest that a key role of Ena, acting downstream of Abl, may be to maintain a constant filopodial organization of the growth cone, even as Abl activity varies in response to guidance cues in the environment.Summary statementWe dissect the function of the actin polymerase, Enabled, in axon growth by live-imaging of actin dynamics and axon morphology of the TSM1 neuron in its native environment in vivo.
Enhancer architecture and chromatin accessibility constrain phenotypic space during development
Authors: Galupa Rafael , Alvarez-Canales Gilberto , Borst Noa Ottilie , Fuqua Timothy , Gandara Lautaro , Misunou Natalia , Richter Kerstin , Alves Mariana R. P. , Karumbi Esther , Perkins Melinda Liu , Kocijan Tin , Rushlow Christine A. , Crocker Justin 
Published: April 2023

ABSTRACTDevelopmental enhancers are DNA sequences that when bound to transcription factors dictate specific patterns of gene expression during development. It has been proposed that the evolution of such cis-regulatory elements is a major source of adaptive evolution; however, the regulatory and evolutionary potential of such elements remains little understood, masked by selective constraints, drift and contingency. Here, using mutation libraries inDrosophila melanogasterembryos, we observed that most mutations in classical developmental enhancers led to changes in gene expression levels but rarely resulted in novel expression outside of the native cell- and tissue-types. In contrast, random sequences often acted as developmental enhancers, driving expression across a range of levels and cell-types, in patterns consistent with transcription factor motifs therein; random sequences including motifs for transcription factors with pioneer activity acted as enhancers even more frequently and resulting in higher levels of expression. Together, our findings suggest that the adaptive phenotypic landscapes of developmental enhancers are constrained by both enhancer architecture and chromatin accessibility. We propose that the evolution of existing enhancers is limited in its capacity to generate novel phenotypes, whereas the activity ofde novoelements is a primary source of phenotypic novelty.QUOTE“Chance and chance alone has a message for us.” Milan Kundera,The Unbearable Lightness of Being
Robust enhancement of motor sequence learning with 4mA transcranial electric stimulation
Authors: Hsu Gavin , Shereen A. Duke , Cohen Leonardo G. , Parra Lucas C. 
Published: April 2023

AbstractBackground and ObjectivesMotor learning experiments with transcranial direct current stimulation (tDCS) at 2mA have produced mixed results. We hypothesize that tDCS will boost motor learning provided sufficiently high field intensity on the motor cortex.MethodsIn a single-blinded, between-subject design, 72 healthy right-handed participants received either anodal or cathodal tDCS at 4mA while they learned to perform a sequence of key presses using their non-dominant hand for about 12 minutes. Cathodal stimulation served as an active control for sensation. A separate sham-stimulation group established baseline performance. Gains during practice and rest periods were analyzed (called micro-online and -offline learning). The target for stimulation was identified on the motor cortex using fMRI. After optimization with individual current flow models, we selected a single montage for all 108 participants with 4 frontal and 4 parietal electrodes each drawing 1mA.ResultsWe found significant gains in performance with anodal stimulation (Cohen’s d=0.7). The boost in performance persisted for at least one hour. Subsequent learning for a new sequence and the opposite hand also improved. Concurrent tDCS enhanced micro-offline learning, while subsequent learning relied on micro-online gains. Sensation ratings were comparable in the active groups and did not exceed moderate levels. The new electrode montage achieved a better tradeoff between stimulation intensity and sensations on the scalp as compared to alternative montages.ConclusionThe present paradigm shows reliable behavioral effects at 4mA and is well-tolerated. It may serve as a go-to experiment for future studies on motor learning and tDCS.HighlightstDCS resulted in a lasting boost of concurrent learning with effect size of Cohen’s d=0.7.Subsequent learning was also improved, indicating a form of meta-learning.Detailed analysis of behavior suggests an effect of tDCS on sequence consolidation.A novel electrode montage with 1mA through each of 4+4 electrodes was well-tolerated.
Bayesian Phylogenetic Inference of HIV Latent Lineage Ages Using Serial Sequences
Authors: Nagel Anna , Rannala Bruce 
Published: April 2023

HIV evolves rapidly within individuals, allowing phylogenetic studies to infer the history of viral lineages on short time scales. Latent HIV sequences are an exception to this rapid evolution, as their transcriptional inactivity leads to negligible mutation rates in comparison to non-latent HIV lineages. Latent sequences are of keen interest as they provide insight into the formation, persistence, and decay of the latent reservoir. Different mutation rates in latent versus active HIV lineages generate potential information about the times at which sequences entered the latent reservoir. A Bayesian phylogenetic method is developed to infer integration times of latent HIV sequences. The method uses informative priors to incorporate biologically sensible bounds on inferences (such as requiring sequences to become latent before being sampled) that many existing methods lack. A new simulation method is also developed, based on widely-used epidemiological models of within-host viral dynamics, and applied to evaluate the new method, showing that point estimates and credible intervals are often more accurate by comparison with existing methods. Accurate estimates of latent integration dates are crucial in dating the formation of the latent reservoir relative to key events during HIV infection, such as the initiation of antiretroviral treatment. The method is applied to analyze publicly-available sequence data from 4 HIV patients, providing new insights regarding the temporal pattern of latent HIV integration events.Significance StatementPhylogenetic studies are increasingly being used to characterize within-host HIV evolution and the temporal dynamics of the HIV latent reservoir in particular, which is not targeted by current treatment methods and thus prevents a cure for HIV. Phylogenetic methods currently used to analyze HIV sequences suffer from conceptual and statistical problems that degrade their performance. A new Bayesian inference method to estimate the ages of latent sequences and a new simulation method based on within-host viral dynamics are developed. The new inference method outperforms existing methods, particularly in characterizing uncertainty. Understanding how the latent HIV reservoir changes overtime will allow researchers to better understand the nature of HIV infection and develop strategies for a cure.
Interplay of Human Metabolome and Gut Microbiome in Major Depression
Authors: Amin Najaf , Liu Jun , Bonnechere Bruno , MehmoudianDehkordi Siamak , Arnold Matthias , Batra Richa , Chiou Yu-Jie , Fernandes Marco , Ikram M. Arfan , Kraaij Robert , Krumsiek Jan , Newby Danielle , Nho Kwangsik , Radjabzadeh Djawad , Saykin Andrew J , Shi Liu , Sproviero William , Winchester Laura , Yang Yang , Nevado-Holgado Alejo J , Kastenmüller Gabi , Kaddurah-Daouk Rima F , van Duijn Cornelia M 
Published: April 2023

AbstractThe pathogenesis of depression is complex involving the interplay of genetic and environmental risk factors including diet, lifestyle and the gut microbiome. Metabolomics studies may shed light on the interplay of these factors. We study over 63,000 individuals including 8462 cases with a lifetime major depression and 5403 cases with recurrent major depression from the UK Biobank profiled for nuclear magnetic resonance (NMR) spectroscopy based metabolites with the Nightingale platform. We identify 124 metabolites that are associated with major depressive disorder (MDD), including 49 novel associations. No differences were seen between the metabolic profiles of lifetime and recurrent MDD. We find that metabolites involved in the tricarboxylic acid (TCA) cycle are significantly altered in patients with MDD. Integrating the metabolic signatures of major depression and the gut microbiome, we find that the gut microbiome might play an important role in the relationship between these metabolites, lipoproteins in particular, and MDD. The orderClostridiales, and the phylaProteobacteriaandBacteroideteswere the most important taxa, which link the lipoprotein particles to MDD. Our study shows that at the molecular level energy metabolism is disturbed in patients with MDD and that the interplay between the gut microbiome and blood metabolome may play a key role in the pathogenesis of MDD.
The discovery of genome-wide mutational dependence in naturally evolving
populations
Authors: Green Anna G. , Vargas Roger , Marin Maximillian G. , Freschi Luca , Xie Jiaqi , Farhat Maha R. 
Published: April 2023

Abstract

Background
Evolutionary pressures on bacterial pathogens can result in phenotypic
change including increased virulence, drug resistance, and transmissibility.
Understanding the evolution of these phenotypes in nature and the multiple
genetic changes needed has historically been difficult due to sparse and
contemporaneous sampling. A complete picture of the evolutionary routes
frequently travelled by pathogens would allow us to better understand
bacterial biology and potentially forecast pathogen population
shifts.

Methods
In this work, we develop a phylogeny-based method to assess evolutionary
dependency between mutations. We apply our method to a dataset of
31,428Mycobacterium tuberculosiscomplex
(MTBC) genomes, a globally prevalent bacterial pathogen with increasing
levels of antibiotic resistance.

Results
We find evolutionary dependency within simultaneously- and
sequentially-acquired variation, and identify that genes with dependent
sites are enriched in antibiotic resistance and antigenic function. We
discover 20 mutations that potentiate the development of antibiotic
resistance and 1,003 dependencies that evolve as a consequence antibiotic
resistance. Varying by antibiotic, between 9% and 80% of resistant strains
harbor a dependent mutation acquired after a resistance-conferring variant.
We demonstrate that mutational dependence can not only improve prediction of
phenotype (e.g. antibiotic resistance), but can also detect sequential
environmental pressures on the pathogen (e.g. the pressures imposed by
sequential antibiotic exposure during the course of standard
multi-antibiotic treatment). Taken together, our results demonstrate the
feasibility and utility of detecting dependent events in the evolution of
natural populations.

Data and code available at:https://github.com/farhat-lab/DependentMutations
Knowledge of COVID-19 Symptoms, Transmission, and Prevention: Evidence from Health and Demographic Surveillance in Southern Mozambique
Authors: Nhacolo Ariel Q. , Madewell Zachary J. , Muir Jonathan A. , Sacoor Charfudin N. , Xerinda Elisio G. , Matsena Teodimiro , Bassat Quique , Whitney Cynthia G. , Mandomando Inácio M. , Cunningham Solveig A. 
Published: April 2023

AbstractOver 230,000 COVID-19 cases and over 2,200 deaths have been reported in Mozambique though May 2023. Understanding community members’ knowledge of SARS-CoV-2 transmission and prevention is essential for directing public health interventions to reduce disease spread and improve vaccination coverage. Here, we describe knowledge of COVID-19 transmission, prevention, and symptoms among community residents in Mozambique. We conducted a cross-sectional survey among 33,087 households in a Health and Demographic Surveillance System in Manhiça, Mozambique. Participants were recruited at the tail end of the Delta variant wave in September 2021 to the peak of Omicron cases in January 2022. Principal components analysis was used to create scores representing knowledge of COVID-19 symptoms, transmission, and prevention. Multiple imputation and quasi-Poisson regression were used to examine associations between demographic characteristics and sources of COVID-19 information, and knowledge of COVID-19 symptoms, transmission, and prevention. We examined whether sources of COVID-19 information mediated the relationship between educational attainment and knowledge of symptoms, transmission, and prevention. Across this rural community, 98.2%, 97.0%, and 85.1% of respondents reported knowing how COVID-19 could be prevented, that SARS-CoV-2 can cause disease, and how SARS-CoV-2 is transmitted, respectively. Most cited symptoms were cough (51.2%), headaches (44.9%), and fever (44.5%); transmission mechanisms were droplets (50.5%) or aerosol (<5 µm diameter) (46.9%) from an infected person; and prevention measures were handwashing (91.9%) and mask-wearing (91.8%). Characteristics associated with greater knowledge of symptoms, transmission, and prevention included having at least primary education, older age, employment, higher wealth, and Christian religion. Respondents who had had COVID-19 symptoms were also more likely to have knowledge of symptoms, transmission, and prevention. Gathering information from TV, WhatsApp, radio, and hospital mediated the relationship between educational attainment and knowledge scores. These findings support the need for outreach and for community-engaged messaging to promote prevention measures, particularly among people with low education.