bluuebunny/crossref_metadata_2025_split huggingface dataset:
Different functions of Lhcx isoforms in photoprotective mechanism in the marine diatomThalassiosira pseudonana
Authors: Nakayasu Mana , Akimoto Seiji , Yoneda Kohei , Ikuta Soichiro , Shimakawa Ginga , Matsuda Yusuke 
Published: April 2024

AbstractPhotosynthesis needs light energy, but that exceeding the maximal capacity of photosynthesis enhances formation of reactive oxygen species, which potentially causes photodamages. Therefore, light-harvesting complexes (Lhc) in phototrophs harbor various proteins and pigments to function in both light capture and energy dissipation. Diatom Lhcx proteins are reported to be a critical component for thermal dissipation of excess light energy, but the molecular mechanism of photoprotection is still not fully understood and the functions of each Lhcx isoform are not yet differentiated. Here, we focused on two types of Lhcx isoforms inThalassiosira pseudonana: TpLhcx1/2, putative major components for energy-dependent fluorescence quenching (qE); and TpLhcx6_1, functionally unknown isoform uniquely conserved in Thalassiosirales. TpLhcx1/2 proteins accumulated more under high light than under low light, while the TpLhcx6_1 protein level was constitutive irrespective of light intensities and CO2 concentrations. High-light induced photodamage of photosystem II was increased in the genome-editing transformants of these Lhcx isoforms relative to the wild-type. Transformants lacking TpLhcx1/2 showed significantly lowered qE capacities, strongly suggesting that these proteins are important for the fast thermal energy dissipation. While in contrast, genome-editing transformants lacking the TpLhcx6_1 protein rather increased the qE capacity. TpLhcx6_1 transformants were further evaluated by the low-temperature time-resolved chlorophyll fluorescence measurement, showing the longer fluorescence lifetime in transformants than that in the wild type cells even at the dark-acclimated state of these cells. These results suggest that TpLhcx6_1 functions in photoprotection through non-photochemical energy dissipation in the different way from qE.One sentence summaryThe marine diatomThalassiosira pseudonanadissipates excess light energy for photoprotectionviatwo types of mechanisms supported by different Lhc isofoms.
Gamified closed-loop non-pharmacological intervention enhances tic suppression in children
Authors: Rotstein Michael S. , Zimmerman-Brenner Sharon , Davidovitch Shiri , Ben-Haim Yael , Koryto Yuval , Sion Romi , Rubinstein Einat , Djerassi Meshi , Lubiniaker Nitzan , Peleg Tammy Pilowsky , Steinberg Tamar , Leitner Yael , Raz Gal 
Published: April 2024

AbstractBackgroundThegamificationof behavioral intervention for tic disorders (TDs) may not only enhance compliance with treatment protocols but also offer a key clinical advantage. By providing immediate positive feedback when tics are suppressed, games can counteract negative reinforcement processes that reinforce tics, which assumingly alleviates unpleasant premonitory urges. We developed a gamified protocol (XTics), which leverages this potential by combining gamified tic triggers with immediate reinforcement of tic suppression. We evaluate the clinical value of immediate reward contingency in enhancing tic suppression performance.MethodsXTics comprises two conditions: tic-contingent and non-contingent. In the ticcontingent version, game progression was determined by real-time input from an experimenter who monitored the participant’s tics, rewarding tic suppression with favorable outcomes. Conversely, in the non-contingent version, game events occurred randomly. Using a crossover design, we trained 35 participants (aged 7-15) in both versions, with each participant undergoing a preliminary behavioral training and three hourly sessions for each condition. We both evaluated the overall protocol’s four-week impact on tic severity measures and compared contingent and non-contingent conditions.ResultsWe achieved complete adherence to the protocol, while the participants increased their tic-free intervals by an average of 558% from the first to the last training day. YGTSS, a clinical measure of tic severity, showed an average clinically meaningful reduction of 25.69±23.39%, which was larger than that observed in control interventions and comparable to the effects of longer non-pharmacological treatments. Parent-reported tic severity decreased by 42.99±31.69% from baseline to three months post-treatment. When contrasting the ticcontingent with the tic-non-contingent training versions, we observed a larger improvement in tic-free interval duration in the former case (t(67)=3.15, p=.0025). Additionally, Rush, another measure of tic severity, demonstrated a greater reduction following training with the contingent compared to the non-contingent version (t(47)=3.47, p=.002).ConclusionThe combination of gamified tic triggering with immediate and contingent rewards demonstrates a promising approach for enhancing treatment efficacy in TDs, offering an engaging boost to traditional therapeutic methods.
Integrating Preconception Risk Assessment and Counseling with Primary Health Care: A Feasibility Assessment
Authors: Dunlop Anne L. , Alfonso Susana , Hansen Nora , Williams Dionne , Marshall Ariela L. , Anderson Victoria M. 
Published: April 2024

ABSTRACTBackgroundProfessional association recommendations call for integrating preconception health promotion with primary care, yet there are scarce tools and implementation research to support practices in doing so.PurposeTo evaluate the feasibility of integrating a preconception health digital risk assessment and virtual coaching into women’s primary care encounters.MethodsIn the Emory Family Medicine Clinic (Atlanta, Georgia), female patients 21-40 years of age with a well-woman or chronic condition encounter scheduled between 9/1/2022 and 5/1/2023 were invited to participate. Consenting patients were provided theFrame Your Futureweblink to complete the digital risk assessment followed by virtual counseling, and their family physicians were provided with a pdf summary to discuss during the primary care encounter. Demographic and clinical information was collected via medical record abstraction and patient and physician experiences via survey.ResultsOf 46 enrolled patients, 44 (96%) made a Frame account, 38 (86%) completed the risk assessment, 34 (89%) completed virtual coaching, and 24 (71%) had a physician discuss their preconception health assessment during the primary care encounter. Nearly 80% of patients reported an increase in confidence in discussing fertility with their physician, and 50% reported they would not otherwise have brought up fertility and preconception health during the encounter. Both patients and physicians were satisfied with the process and viewed it as helping motivate positive changes in patient health and health behaviors.ConclusionThe completion of preconception digital risk assessment and virtual counseling facilitates discussion of preconception health during primary care encounters and shows promise for improving women’s health.
Projecting international mpox spread in Asia: ongoing global health risk
Authors: Asakura Toshiaki R. , Jung Sung-mok , Murayama Hiroaki , Ghaznavi Cyrus , Sakamoto Haruka , Teshima Ayaka , Miura Fuminari , Endo Akira 
Published: April 2024

AbstractThe global mpox outbreak affected many Asian countries in 2023, following a sustained local transmission in Japan. Given the large population sizes and limited vaccine rollout in Asia, the potential risk of global mpox reemergence arising from Asia is of concern. Using a mathematical model incorporating heterogeneous sexual networks among MSM, calibrated to incidence data in Japan, we projected the patterns of international mpox spread across 42 Asian countries. Our simulations highlight countries at a high risk of mpox introductions, many of which were low- and middle-income countries (LMICs) in South-eastern Asia. Our analysis also suggests a shifting focus of importation risk from Eastern Asia to South-eastern Asia, and subsequently to Central, Southern and Western Asia, which roughly coincided with the observed spread patterns in 2023. Global cooperation and support are warranted, especially for LMICs with an elevated risk of mpox introduction, to minimise the risk of continued circulation in Asia and beyond.
Topical Steroid Withdrawal is a Targetable Excess of Mitochondrial NAD+
Authors: Shobnam Nadia , Saksena Sarini , Ratley Grace , Yadav Manoj , Chaudhary Prem Prashant , Sun Ashleigh A , Howe Katherine N , Gadkari Manasi , Franco Luis M , Ganesan Sundar , McCann Katelyn J , Hsu Amy P , Kanakabandi Kishore , Ricklefs Stacy , Lack Justin , Yu Weiming , Similuk Morgan , Walkiewicz Magdalena A ,   NIAID Centralized Sequencing Program, Gardner Donna D , Barta Kelly , Tullos Kathryn , Myles Ian A 
Published: April 2024

AbstractBackgroundTopical corticosteroids (TCS) are first-line therapies for numerous skin conditions. Topical Steroid Withdrawal (TSW) is a controversial diagnosis advocated by patients with prolonged TCS exposure who report severe systemic reactions upon treatment cessation. However, to date there have been no systematic clinical or mechanistic studies to distinguish TSW from other eczematous disorders.MethodsA re-analysis of a previous survey with eczematous skin disease was performed to evaluate potential TSW distinguishing symptoms. We subsequently conducted a pilot study of 16 patients fitting the proposed diagnostic criteria. We then performed: tissue metabolomics, transcriptomics, and immunostaining on skin biopsies; serum metabolomics and cytokine assessments; shotgun metagenomics on microbiome skin swabs; genome sequencing; followed by functional, mechanistic studies using human skin cell lines and mice.ResultsClinically distinct TSW symptoms included burning, flushing, and thermodysregulation. Metabolomics and transcriptomics both implicated elevated NAD+ oxidation stemming from increased expression of mitochondrial complex I and conversion of tryptophan into kynurenine metabolites. These abnormalities were induced by glucocorticoid exposure bothin vitroand in a cohort of healthy controls (N=19) exposed to TCS. Targeting complex I via either metformin or the herbal compound berberine improved outcomes in both cell culture and in an open-label case series for patients with TSW.ConclusionTaken together, our results suggest that TSW has a distinct dermatopathology. While future studies are needed to validate these results in larger cohorts, this work provides the first mechanistic evaluation into TSW pathology, and offers insights into clinical identification, pharmacogenomic candidates, and directed therapeutic strategies.
Immune escape and attenuated severity associated with the SARS-CoV-2 BA.2.86/JN.1 lineage
Authors: Lewnard Joseph A. , Mahale Parag , Malden Debbie , Hong Vennis , Ackerson Bradley K. , Lewin Bruno J. , Link-Gelles Ruth , Feldstein Leora R. , Lipsitch Marc , Tartof Sara Y. 
Published: April 2024

ABSTRACTThe SARS-CoV-2 BA.2.86 lineage, and its sublineage JN.1 in particular, achieved widespread transmission in the US during winter 2023-24. However, the increase in infections was not accompanied by increases in COVID-19 hospitalizations and mortality commensurate with prior waves. To understand shifts in COVID-19 epidemiology associated with JN.1 emergence, we compared characteristics and clinical outcomes of time-matched cases infected with BA.2.86- derived lineages (predominantly representing JN.1) versus co-circulating XBB-derived lineages in December, 2023 and January, 2024. Cases infected with BA.2.86-derived lineages received greater numbers of COVID-19 vaccine doses, including XBB.1.5-targeted and BA.4/BA.5-targeted boosters, in comparison to cases infected with XBB-derived lineages. Additionally, cases infected with BA.2.86-derived lineages experienced greater numbers of documented prior SARS-CoV-2 infections. These associations of BA.2.86-derived lineages with immune escape were confirmed when comparing cases diagnosed during periods when JN.1 was the predominant circulating lineage to cases diagnosed during November, 2023. Cases infected with BA.2.86-derived lineages, or during periods when JN.1 was the predominant circulating lineage, also experienced lower risk of progression to severe clinical outcomes requiring emergency department consultations or hospital admission. Sensitivity analyses suggested under-ascertainment of prior infections, even if differential between cases infected with BA.2.86-derived lineages and non-BA.2.86 lineages, could not explain this apparent attenuation of severity. Our findings implicate escape from immunity acquired from prior vaccination or infection in the emergence of the JN.1 lineage and suggest infections with this lineage are less likely to experience clinically-severe disease. Monitoring of immune escape and clinical severity in emerging SARS-CoV-2 variants remains a priority to inform responses.
The landscape and level of alcohol policy enforcement in Tanzania
Authors: Madundo Kim , Hudda Aliza , Seekles Maaike L. , Mmbaga Blandina , Obasi Angela 
Published: April 2024

AbstractHarmful use of alcohol causes more deaths in Sub-Saharan Africa than in any other region. In Tanzania, where alcohol use disorders rates are twice the overall African average, harmful alcohol consumption is a public health concern. Given the lack of a contemporary overview of the alcohol policy landscape, we conducted a mixed-methods review of key alcohol-related policies, implementers, and initiatives in Tanzania. We conducted a desk-based review of policy-related documents, and in-depth interviews with eight key informants guided by the 10-composite-indicator framework of a tool for measuring alcohol policy implementation developed by World Health Organization. Representatives were from health-service delivery, community-based organizations, governmental organizations, research, and policymakers whose work is related to alcohol in Tanzania. Data was collected in October 2021, June 2022, and finalized in March 2023. Findings were analyzed using Microsoft Word v2021. Themes were identified, collected, combined, and tabulated. Differences were then resolved by first and second authors. Our findings revealed no single comprehensive national alcohol policy. Pending finalization of a draft policy, various documents and actors govern alcohol production, distribution, licensing, and consumption. Little intersectoral linkage between entities contributes to poor enforcement of these regulations. Regulation is stronger in urban areas, and restrictions more effective on industrial alcohol. However, the majority of consumed alcohol in Tanzania is informally-produced, especially in rural settings. Socio-cultural context plays a key role in alcohol production and consumption, contributing to early-age exposure to alcohol. Alcohol is a growing source of revenue for the Tanzanian government and, therefore, imposing further restrictions is a low priority. There are important policy gaps in various sectors pertaining to alcohol regulation. Our results strongly suggest the need for a comprehensive approach to developing an overarching alcohol policy, with involvement of key stakeholders, stronger enforcement, and increased awareness, resources, and collaborations.
A Framework for Evaluating the Efficacy of Foundation Embedding Models in Healthcare
Authors: Xu Sonnet , Gui Haiwen , Rotemberg Veronica , Wang Tongzhou , Chen Yiqun T. , Daneshjou Roxana 
Published: April 2024

AbstractRecent interest has surged in building large-scale foundation models for medical applications. In this paper, we propose a general framework for evaluating the efficacy of these foundation models in medicine, suggesting that they should be assessed across three dimensions: general performance, bias/fairness, and the influence of confounders. Utilizing Google’s recently released dermatology embedding model and lesion diagnostics as examples, we demonstrate that: 1) dermatology foundation models surpass state-of-the-art classification accuracy; 2) general-purpose CLIP models encode features informative for medical applications and should be more broadly considered as a baseline; 3) skin tone is a key differentiator for performance, and the potential bias associated with it needs to be quantified, monitored, and communicated; and 4) image quality significantly impacts model performance, necessitating that evaluation results across different datasets control for this variable. Our findings provide a nuanced view of the utility and limitations of large-scale foundation models for medical AI.
Phylogenomic reconstruction ofCryptosporidiumspp. captured directly from clinical samples reveals extensive genetic diversity
Authors: Khan A. , Alves-Ferreira E.V.C. , Vogel H. , Botchie S. , Ayi I. , Pawlowic M.C. , Robinson G. , Chalmers R.M. , Lorenzi H. , Grigg M.E. 
Published: April 2024

AbstractCryptosporidiumis a leading cause of severe diarrhea and mortality in young children and infants in Africa and southern Asia. More than twentyCryptosporidiumspecies infect humans, of whichC. parvumandC. hominisare the major agents causing moderate to severe diarrhea. Relatively few genetic markers are typically applied to genotype and/or diagnoseCryptosporidium. Most infections produce limited oocysts making it difficult to perform whole genome sequencing (WGS) directly from stool samples. Hence, there is an immediate need to apply WGS strategies to 1) develop high-resolution genetic markers to genotype these parasites more precisely, 2) to investigate endemic regions and detect the prevalence of different genotypes, and the role of mixed infections in generating genetic diversity, and 3) to investigate zoonotic transmission and evolution. To understandCryptosporidiumglobal population genetic structure, we applied Capture Enrichment Sequencing (CES-Seq) using 74,973 RNA-based 120 nucleotide baits that cover ∼92% of the genome ofC. parvum. CES-Seq is sensitive and successfully sequencedCryptosporidiumgenomic DNA diluted up to 0.005% in human stool DNA. It also resolved mixed strain infections and captured new species ofCryptosporidiumdirectly from clinical/field samples to promote genome-wide phylogenomic analyses and prospective GWAS studies.
Genotypic Characterization and Antimicrobial Susceptibility of HumanCampylobacter jejuniIsolates in Southern Spain
Authors: Fernández-Palacios Pablo , Galán-Sánchez Fátima , Casimiro-Soriguer Carlos S , Jurado-Tarifa Estefanía , Arroyo Federico , Lara María , Chaves J. Alberto , Dopazo Joaquín , Rodríguez-Iglesias Manuel A. 
Published: April 2024

AbstractCampylobacter jejuniis the main cause of bacterial gastroenteritis and a public health problem worldwide. Little information is available on the genotypic characteristics of humanCampylobacter jejuniin Spain. This study is based on an analysis of the resistome, virulome and phylogenetic relationship, antibiogram prediction and antimicrobial susceptibility of 114 human isolates ofC. jejunifrom a tertiary hospital in southern Spain from October 2020 to June 2023. The isolates were sequenced using Illumina technology, and bioinformatic analysis was subsequently performed. The susceptibility ofC. jejuniisolates to ciprofloxacin, tetracycline, and erythromycin was tested. A high resistance rate was obtained for ciprofloxacin (90.6%) and tetracycline (66.7%), and a low resistance rate for erythromycin (0.85%) was detected among theC. jejuniisolates. CC-21 (n=23), ST-572 (n = 13) and ST-6532 (n=13) were the most prevalent clonal complexes (CCs) and sequence types (STs). Concerning the virulome, thecadF, ciaB, andcdtABCgenes were detected in all the isolates. A prevalence of 20.1% was obtained for the geneswlaNandcstIII, which are related to the pathogenesis of Guillain-Barré syndrome (GBS). The prevalence of the main antimicrobial resistance markers detected werecmeABC(92.1%),RE-cmeABC(7.9%), the T86I substitution ingyrA(88.9%),blaOXA-61(72.6%), tet(O)(65.8%) andant(6)-Ia(17.1%). High antibiogram prediction rates (>97%) were obtained except for the erythromycin-resistant phenotype. This study contributes significantly to the knowledge ofCampylobacter jejunigenomics for the prevention, treatment and control of infections caused by this pathogen, which is relevant to public health.ImportanceDespite being the pathogen with the greatest number of gastroenteritis cases worldwide,Campylobacter jejuniremains a poorly studied microorganism. The development of whole-genome sequencing (WGS) techniques has led to a better understanding of the genotypic characteristics of this pathogen. These techniques complement the data obtained from the phenotypic analysis ofC. jejuniisolates. The zoonotic transmission ofC. jejunithrough the consumption of contaminated poultry implies approaching the study of this pathogen through the term “One Health.” This is the first study, using WGS, conducted on human isolates ofC. jejuniin Spain to date, which allows comparison of the results obtained with similar studies conducted in other countries and with animal and environmental isolates.
Proinflammatory stress activates neutral sphingomyelinase 2 based generation of a ceramide-enriched β cell EV subpopulation
Authors: Xu Jerry , Harris-Kawano Arianna , Enriquez Jacob R. , Mirmira Raghavendra G. , Sims Emily K. 
Published: April 2024

Abstractβ cell extracellular vesicles (EVs) play a role as paracrine effectors in islet health, yet mechanisms connecting β cell stress to changes in EV cargo and potential impacts on diabetes remain poorly defined. We hypothesized that β cell inflammatory stress engages neutral sphingomyelinase 2 (nSMase2)-dependent EV formation pathways, generating ceramide-enriched EVs that could impact surrounding β cells. Consistent with this, proinflammatory cytokine treatment of INS-1 β cells and human islets concurrently increased β cell nSMase2 and ceramide expression, as well as EV ceramide staining. Direct chemical activation or genetic knockdown of nSMase2, or treatment with a GLP-1 receptor agonist also modulated cellular and EV ceramide. Small RNA sequencing of ceramide-enriched EVs identified a distinct set of miRNAs linked to β cell function and identity. Coculture experiments using CD9-GFP tagged INS-1 cell EVs demonstrated that either cytokine treatment or chemical nSMase2 activation increased EV transfer to recipient cells. Children with recent-onset T1D showed no abnormalities in circulating ceramide-enriched EVs, suggesting a localized, rather than systemic phenomenon. These findings highlight nSMase2 as a regulator of β cell EV cargo and identify ceramide-enriched EV populations as a contributor to EV-related paracrine signaling under conditions of β cell inflammatory stress.Article Highlightsa.Why did we undertake this study?Mechanisms connecting β cell stress to changes in extracellular vesicle (EV) cargo and potential impacts on diabetes are poorly defined.b.What is the specific question we wanted to answer?Does β cell inflammatory stress engage neutral sphingomyelinase 2 (nSMase2)-dependent EV formation pathways to generate ceramide-enriched EVs.c.What did we find?Proinflammatory cytokine treatment of β cells increased β cell ceramide expression, along with EV ceramide in part via increases in nSMase2. Ceramide-enriched EVs housed a distinct set of miRNAs linked to insulin signaling. Both cytokine treatment and nSMase2 activation increase EV transfer to other β cells.d.What are the implications of our findings?Our findings highlight nSMase2 as a regulator of β cell EV cargo and identify ceramide-enriched EV populations as a contributor to EV-related paracrine signaling under conditions of β cell inflammatory stress.