bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and laboratory features of COVID-19 illness and outcomes in immunocompromised individuals during the first pandemic wave in Sydney, Australia
Authors: Dharan Nila J. , Sasson Sarah C. , Ahlenstiel Golo , Andersen Christopher R. , Bloch Mark , Buckland Griselda , Hamad Nada , Han Win Min , Kelleher Anthony D. , Long Georgina V. , Matthews Gail V. , Mina Michael M. , Papot Emmanuelle , Petoumenos Kathy , Swaminathan Sanjay , Withers Barbara , Yun James , Polizzotto Mark N.
Published: August 2023

People with immunocompromising conditions are at increased risk of SARS-CoV-2 infection and mortality, however early in the pandemic it was challenging to collate data on this heterogenous population. We conducted a registry study of immunocompromised individuals with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection from March – October 2020 in Sydney, Australia to understand clinical and laboratory outcomes in this population prior to the emergence of the Delta variant. 27 participants were enrolled into the study including people with a haematologic oncologic conditions (n=12), secondary immunosuppression (N=8) and those with primary or acquired immunodeficiency (i.e. HIV; N=7). All participants had symptomatic COVID-19 with the most common features being cough (64%), fever (52%) and headache (40%). Five patients demonstrated delayed SARS-CoV-2 clearance lasting three weeks to three months. The mortality rate in this study was 7% compared to 1.3% in the state of New South Wales Australia during the same period. This study provides data from the first eight months of the pandemic on COVID-19 outcomes in at-risk patient groups.
Functional Connectivity and Complexity Analyses of Resting-State fMRI in Pre-Adolescents with ADHD
Authors: Zhang Ru , Murray Stuart B. , Duval Christina J. , Wang Danny J.J. , Jann Kay
Published: August 2023

Attention deficit hyperactivity disorder (ADHD) has been characterized by impairments among distributed functional brain networks, e.g., the frontoparietal network (FPN), default mode network (DMN), and reward and motivation-related circuits (RMN). In the current study, we evaluated the complexity and functional connectivity (FC) of resting state fMRI (rsfMRI) in pre-adolescents with ADHD for pathology-relevant networks.

We leveraged data from the Adolescent Brain and Cognitive Development (ABCD) Study. The final study sample included 63 children with ADHD and 92 healthy control children matched on age, sex, and pubertal development status. For selected regions in relevant networks, ANCOVA compared multiscale entropy (MSE) and FC between the groups. Finally, differences in the association between MSE and FC were evaluated.

We found significantly reduced MSE along with increased FC within the FPN of pre-adolescents with ADHD compared to matched healthy controls. Significant partial correlations between MSE and FC emerged in fewer regions in the participants with ADHD than in the controls.

The observation of reduced entropy is consistent with existing literature using rsfMRI and other neuroimaging modalities. The current findings of complexity and FC in ADHD support hypotheses of altered function of inhibitory control networks in ADHD.
Genomic and eco-epidemiological investigations in Uruguay reveal local Chikungunya virus transmission dynamics during its expansion across the Americas in 2023
Authors: Burgueño Analía , Giovanetti Marta , Fonseca Vagner , Morel Noelia , Lima Mauricio , Castro Emerson , Guimarães Natália R. , Iani Felipe C. M. , Bormida Victoria , Cortinas Maria Noel , Ramas Viviana , Coppola Leticia , Bento Ana I. , Franco Leticia , Rico Jairo Mendez , Lourenço José , Alcantara Luiz Carlos Junior , Chiparelli Hector
Published: August 2023

Uruguay experienced its first Chikungunya virus outbreak in 2023, resulting in a significant burden to its healthcare system. We conducted analysis based on real-time genomic surveillance (30 novel whole genomes) to offer timely insights into recent local transmission dynamics and eco-epidemiological factors behind its emergence and spread in the country.
India Hypertension Control Initiative- Blood Pressure Control using Drug and Dose-Specific Standard Treatment Protocol at Scale in Punjab and Maharashtra, India, 2022
Authors: Kaur Prabhdeep , Sakthivel Manikandanesan , Venkatasamy Vettrichelvan , Jogewar Padmaja , Gill Sandeep S , Kunwar Abhishek , Sharma Meenakshi , Pathni Anupam Khungar , Durgad Kiran , Sahoo Swagata Kumar , Wankhede Amol , Kumar Navneet , Bharadwaj Vishwajit , Das Bidisha , Chavan Tejpalsinh , Khedkar Suhas , Sarode Lalit , Bangar Sampada D , Krishna Ashish , Shivashankar Roopa , Ganeshkumar Parasuraman , Pragya Pragati , Bhargava Balram
Published: August 2023

Background

Hypertension treatment coverage is low in India. A stepwise simple treatment protocol is one of the strategies to improve hypertension treatment in primary care. We estimated the effectiveness of various protocol steps to achieve blood pressure (BP) control in public sector health facilities in Punjab and Maharashtra, India, where the India Hypertension Control Initiative (IHCI) was implemented.

Methods

We analyzed the records of people enrolled for hypertension treatment and follow-up under IHCI between January 2018 and December 2021 in public sector primary and secondary care facilities across 23 districts from two states. Each state followed a different treatment protocol. We calculated the proportion with controlled BP at each step of the protocol. We also estimated the mean decline in BP pre-and post-treatment.

Results

Of 281,209 patients initiated on Amlodipine 5 mg, 159,292 continued on protocol drugs and came for a follow-up visit during the first quarter of 2022. Of 33,450 individuals who came for the follow-up in Punjab and 125,842 in Maharashtra, 70% and 76% had controlled BP, respectively, at the first step with Amlodipine 5 mg. In Punjab, at the second step with amlodipine 10 mg, the cumulative BP control increased to 75%. A similar 5% (76% to 81%) increase was seen in the second step after adding Telmisartan 40 mg in Maharashtra. Overall, the mean (SD) systolic blood pressure (SBP) decreased by 16 mmHg from 148 (15) mmHg at the baseline in Punjab. In Maharashtra, the decline in the mean (SD) SBP was about 15 mmHg from the 144 (18) mmHg baseline.

Conclusion

Simple drug- and dose-specific protocols helped achieve a high control rate among patients retained in care under program conditions. We recommend treatment protocols starting with a single low-cost drug and escalating with the same or another antihypertensive drug depending on the cost and availability.
Prevalence of plantar ulcer and its risk factors in leprosy: a systematic review and meta-analysis
Authors: Govindasamy Karthikeyan , Darlong Joydeepa , Watson Samuel I , Gill Paramjit
Published: August 2023

Background

Plantar ulcers are a leading complication of leprosy that requires frequent visits to hospital and is associated with stigma. The extent of burden of ulcers in leprosy and its risk factors are scant impeding the development of targeted interventions to prevent and promote healing of ulcers. The aim of this review is to generate evidence on the prevalence of plantar ulcer and its risk factors in leprosy.

Methodology/Principal findings

Databases (Medline, Embase, Web of Science, CINAHL, BVS), conference abstracts and reference lists were searched for eligible studies. Studies were included that reported a point prevalence of plantar ulcer and/or its “risk factors” associated with development of ulcers (either causatively or predictively), including individual level, disease related and bio-mechanical factors. We followed PRISMA guidelines for this review. Random-effects meta-analysis was undertaken to estimate the pooled point prevalence of ulcers. Reported risk factors in included studies were narratively synthesised. This review is registered in PROSPERO: CRD42022316726.

Overall, 15 studies (8 for prevalence of ulcer and 7 for risk factors) met the inclusion criteria. The pooled point prevalence of ulcer was 34% (95% CIs: 21%, 46%) and 7% (95% CIs: 4%, 11%) among those with foot anaesthesia and among all people affected by leprosy, respectively. Risk factors for developing ulcers included: unable to feel 10 grams of monofilament on sensory testing, pronated/hyper-pronated foot, foot with peak plantar pressure, foot with severe deformities, and those with lower education and the unemployed.

Conclusions/Significance

The prevalence of plantar ulceration in leprosy is as high as 34% among those with loss of sensation in the feet. However, the incidence and recurrence rates of ulceration are least reported. The inability to feel 10 grams of monofilament appears to be a strong predictor of those at risk of developing ulcers. However, there is a paucity of evidence on identifying those at risk of developing plantar ulcers in leprosy. Prospective studies are needed to estimate the incidence of ulcers. Identifying individuals at risk of ulcers will help design targeted interventions to minimize risk factors, prevent ulcers and promote ulcer healing.
Proteome-Wide Association Studies for Blood Lipids and Comparison with Transcriptome-Wide Association Studies
Authors: Zhang Daiwei , Gao Boran , Feng Qidi , Manichaikul Ani , Peloso Gina M. , Tracy Russell P. , Durda Peter , Taylor Kent D. , Liu Yongmei , Johnson W. Craig , Gabriel Stacey , Gupta Namrata , Smith Joshua D. , Aguet Francois , Ardlie Kristin G. , Blackwell Thomas W. , Gerszten Robert E. , Rich Stephen S. , Rotter Jerome I. , Scott Laura J. , Zhou Xiang , Lee Seunggeun
Published: August 2023

Blood lipid traits are treatable and heritable risk factors for heart disease, a leading cause of mortality worldwide. Although genome-wide association studies (GWAS) have discovered hundreds of variants associated with lipids in humans, most of the causal mechanisms of lipids remain unknown. To better understand the biological processes underlying lipid metabolism, we investigated the associations of plasma protein levels with total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL) in blood. We trained protein prediction models based on samples in the Multi-Ethnic Study of Atherosclerosis (MESA) and applied them to conduct proteome-wide association studies (PWAS) for lipids using the Global Lipids Genetics Consortium (GLGC) data. Of the 749 proteins tested, 42 were significantly associated with at least one lipid trait. Furthermore, we performed transcriptome-wide association studies (TWAS) for lipids using 9,714 gene expression prediction models trained on samples from peripheral blood mononuclear cells (PBMCs) in MESA and 49 tissues in the Genotype-Tissue Expression (GTEx) project. We found that although PWAS and TWAS can show different directions of associations in an individual gene, 40 out of 49 tissues showed a positive correlation between PWAS and TWAS signed p-values across all the genes, which suggests a high-level consistency between proteome-lipid associations and transcriptome-lipid associations.
High-throughput Extracellular Matrix Proteomics of Human Lungs Enabled by Photocleavable Surfactant and diaPASEF
Authors: Bayne Elizabeth F. , Buck Kevin M. , Towler Anna G. , Zhu Yanlong , Pergande Melissa , Zhou Tianhua , Price Scott , Rossler Kalina J. , Morales-Tirado Vanessa , Lloyd Sarah , Wang Fei , He Yupeng , Tian Yu , Ge Ying
Published: August 2023

The extracellular matrix (ECM) is a complex assembly of proteins that provide interstitial scaffolding and elastic recoil to human lungs. The pulmonary extracellular matrix (ECM) is increasingly recognized as an independent bioactive entity by creating biochemical and mechanical signals that influence disease pathogenesis, making it an attractive therapeutic target. However, the pulmonary ECM proteome (“matrisome”) remains challenging to analyze by mass spectrometry due to its inherent biophysical properties and relatively low abundance. Here, we introduce a strategy designed for rapid and efficient characterization of the human pulmonary ECM using the photocleavable surfactant Azo. We coupled this approach with trapped ion mobility MS with diaPASEF to maximize depth of matrisome coverage. Using this strategy, we identify nearly 400 unique matrisome proteins with excellent reproducibility that are known to be important in lung biology, including key insoluble ECM proteins.
Linking the pathway from social media health information seeking to health misinformation sharing: A moderated serial mediation model
Authors: Luo Chen , Tang Yulong , Deng Yuying , Li Yuru
Published: August 2023

Seeking health information from social media has become prominent in recent years. Meanwhile, the proliferation of online health misinformation keeps abreast of this tendency and sparks grave concerns. Drawing upon the S-O-R (Stimulus-Organism-Response) model and the cognitive load theory, the current study aims to clarify the relationship between social media health information seeking and health misinformation sharing with a focus on the Chinese middle-aged or above group, which has been deemed susceptible to online misinformation. Results of structural equation modeling based on an online survey (N= 388) disclosed a serial mediation process with health information overload and misperceptions as sequential mediators. Interestingly, while health misperceptions were positively related to misinformation sharing intention, health information overload was not. Furthermore, as a critical information processing predisposition, the need for cognition only buffered the positive association between information seeking and information overload. Overall, besides proposing a moderated serial mediation model to better comprehend the psychological mechanism underlying health misinformation sharing, this study highlights the importance of zooming into the organism part and the necessity of distinguishing between information overload and misperceptions in the context of health misinformation. Theoretical implications for unraveling online health misinformation sharing and practical implications for boosting immunity against health misinformation among at-risk groups are discussed.
Weekly Intra-Treatment Diffusion Weighted Imaging Dataset for Head and Neck Cancer Patients Undergoing MR-linac Treatment
Authors: El-Habashy Dina M , Wahid Kareem A , He Renjie , McDonald Brigid A , Mulder Samuel J. , Ding Yao A , Salzillo Travis C , Lai Stephen , Christodouleas John , Dresner Alex , Wang Jihong , Naser Mohamed A , Fuller Clifton David , Mohamed Abdallah Sherif Radwan
Published: August 2023

Radiation therapy (RT) is a crucial treatment for head and neck squamous cell carcinoma (HNSCC), however it can have adverse effects on patients' long-term function and quality of life. Biomarkers that can predict tumor response to RT are being explored to personalize treatment and improve outcomes. While tissue and blood biomarkers have limitations, imaging biomarkers derived from magnetic resonance imaging (MRI) offer detailed information. The integration of MRI and a linear accelerator in the MR-Linac system allows for MR-guided radiation therapy (MRgRT), offering precise visualization and treatment delivery. This data descriptor offers a valuable repository for weekly intra-treatment diffusion-weighted imaging (DWI) data obtained from head and neck cancer patients. By analyzing the sequential DWI changes and their correlation with treatment response, as well as oncological and survival outcomes, the study provides valuable insights into the clinical implications of DWI in HNSCC.
ChatENT: Augmented Large Language Model for Expert Knowledge Retrieval in Otolaryngology - Head and Neck Surgery
Authors: Long Cai , Subburam Deepak , Lowe Kayle , Santos André dos , Zhang Jessica , Hwang Sang , Saduka Neil , Horev Yoav , Su Tao , Cote David , Wright Erin
Published: August 2023

Background

The recent surge in popularity of Large Language Models (LLMs), such as ChatGPT, has showcased their proficiency in medical examinations and potential contributions to medical education. However, LLMs possess inherent limitations, including inconsistent accuracy, specific prompting requirements, and the risk of generating harmful hallucinations. A domain-specific, fine-tuned model would address these limitations effectively.

Methods

OHNS-relevant data was systematically gathered from open-access internet sources and indexed into a database. We leveraged Retrieval-Augmented Language Modeling (RALM) to recall this information and used it for pre-training, which was then integrated into ChatGPT 4·0, creating a OHNS specific knowledge Q&A platform known as ChatENT.

Findings

ChatENT showed enhanced performance in the analysis and interpretation of OHNS information, outperforming ChatGPT 4.0 in both the Canadian Royal College OHNS sample examination questions challenge and the US board practice questions challenge, with a 58.4% and 26·0% error reduction, respectively. ChatENT generated fewer hallucinations and demonstrated greater consistency.

Interpretation

To the best of our knowledge, ChatENT is the first specialty-specific LLM in the medical field. It appears to have considerable promise in areas such as medical education, patient education, and clinical decision support. The fine-tuned model has demonstrated the capacity to overcome the limitations of existing LLMs, thereby signaling a future of more precise, safe, and user-friendly applications in the realm of OHNS.

Funding

The authors received no financial support for the research, authorship, and/or publication of this project.
The minimum intervention principle of optimal control relates the uncontrolled manifold to muscle synergies
Authors: Sharma Neelima
Published: August 2023

The nervous system uses muscle activation patterns to perform successful motor tasks, and motor tasks inevitably satisfy the laws of mechanics. The number of muscles usually exceeds the degrees of freedom of the task such that multiple combinations of muscle activities satisfy mechanical demands. A low-dimensional space usually explains a large variance in the muscle activations, leading to the hypothesis that muscle redundancy is solved by neurally coordinated muscle synergies. In addition to synergies, motor task mechanics also enforce a structure on muscle activity. Muscles satisfy multiple non-negotiable mechanical demands of equilibrium, stability, force, and respect the constraints. The redundancy in the muscle architecture is the degree of freedom available after accounting for the necessary mechanics. In this study, I investigate how task mechanics structure muscle activities by using a biomechanical model of an index finger in contact and published measurements of seven muscle activities during a fingertip force production task. I derive a map from muscle activities to complete task mechanics with the necessary conditions of equilibrium, stability, and force. By invoking the uncontrolled manifold hypothesis, I show that the variability in muscle activities is channeled in the task-irrelevant directions, which is given by the null space of the map from muscle activations to task variables. Furthermore, I show that the principal component that explains maximum variance in muscle activations is oriented along the task-irrelevant direction with the highest projected variance, suggesting that the maximal principal directions correspond to the task-irrelevant subspace rather than the task-relevant directions. This study has consequences for understanding muscular redundancy and synergy, and also provides direct evidence that the simplified biomechanical models satisfy mechanical requirements.
How do household living conditions and gender-related decision-making influence child stunting in Rwanda? A population-based study
Authors: Utumatwishima Jean N. , Mogren Ingrid , Umubyeyi Aline , Mansourian Ali , Krantz Gunilla
Published: August 2023

Child stunting (chronic undernutrition) is a major public health concern in low- and middle-income countries. In Rwanda, an estimated 33% of children are affected. This study investigated the household living conditions and the impact of gender-related decision-making on child stunting. The findings contribute to ongoing discussion on this critical public health issue. In December 2021, a population-based cross-sectional study was conducted in Rwanda’s Northern Province; 601 women with children aged 1–36 months were included. Stunting was assessed using low height-for-age criteria. The Multidimensional Poverty Index (MPI) was used to determine household socioeconomic status. Researcher-designed questionnaires evaluated gender-related factors such as social support and household decision-making. Multivariable logistic regression analysis identified risk factor patterns. Six hundred and one children were included in the study; 27.1% (n=163) were diagnosed as stunted; there was a higher prevalence of stunting in boys (60.1%) than girls (39.9%; p<0.001). The MPI was 0.265 with no significant difference between households with stunted children (MPI, 0.263; 95% confidence interval [CI], 0.216–0.310) and non-stunted children (MPI, 0.265; 95% CI, 0.237–0.293). Most households reported a lack of adequate housing (78.9%), electricity (63.0%), good water sources (58.7%), and proper toilets (57.1%). Male-headed households were predominant (92% vs 8.0%;p=0.018), although women often shared decision-making with their partners; 26.4% of the women reported they were forced to have sexual intercourse within marriage (p=0.028). Lack of support during illness (odds ratio [OR], 1.93; 95% CI, 1.13–3.28) and absence of personal guidance (OR, 2.44; 95% CI, 1.41–4.26) were significantly associated with child stunting (p=0.011). Poverty contributes to child stunting in the Northern Province of Rwanda. Limited social support and women’s lack of decision-making power in the household increase stunting rates. Interventions should empower women and address the broader social and economic context to promote both women’s and children’s health.
Unveiling Local Radiation Events through Metagenome Assembled Genomes of Archaea and Bacteria in Hypersaline Microbial Mats from the Archean Domes Site, Cuatro Cienegas, Coahuila, Mexico
Authors: Rodríguez Cruz Ulises Erick E , Castelán-Sánchez Hugo G , Madrigal-Trejo David , Eguiarte Luis Enrique , Souza Valeria
Published: August 2023

A comprehensive study was conducted in the Cuatro Cienegas Basin (CCB) in Coahuila, Mexico, known for its remarkable microbiological diversity and unique physicochemical properties. The ″Archaean Domes ″ (DA) in the CCB are hypersaline, non-lithifying microbial mats. This study focused on analyzing the small domes and circular structures formed in DA through metagenome assembly genomes (MAGs) with the aim of finding new microorganisms and providing information on the tree of life in a place as diverse as the CCB. In total, 329 MAGs were identified, including 52 archaea and 277 bacteria. Remarkably, 30 Archaea and 154 Bacteria could not be classified at the genus level, highlighting the remarkable diversity of CCB. The CCBs showed significant diversity at the phylum level, with Proteobacteria being the most abundant, followed by Euryarchaeota, Firmicutes, Bacteroidetes, Actinobacteria, Cyanobacteria, Spirochaetes, Chloroflexi, Planctomycetes, Candidatus Parvarchaeota, Verrucomicrobia, Balneolaeota, Nitrospirae, and Tenericutes. Subsequently, the MAGs were classified into a phylogenetic tree. In Archaea, monophyletic groups MAGs belonged to the phyla Archaeoglobi, Candidatus Aenigmarchaeota, Candidatus Nanoarchaeota, Candidatus Lokiarchaeota, and Halobacteriota. Among the Bacteria, monophyletic groups were identified as well, including Spirochaetes, Proteobacteria, Planctomycetota, Actinobacteria, Verrucomicrobiota, Bacteroidetes, Bipolaricaulota, Desulfobacterota, and Cyanobacteria. These monophyletic clusters may indicate radiation events that are likely influenced by geographical isolation as well as extreme environmental conditions reported in AD pond like phosphorus deficiency (122:42:1 C:N:P), fluctuating pH and a salinity of 5.28%
Development and Validation of the Mentoring in Undergraduate Research Survey
Authors: Limeri Lisa B. , Carter Nathan T. , Hess Riley A. , Tuma Trevor T. , Koscik Isabelle , Morrison Alexander J. , Outlaw Briana , Royston Kathren Sage , Bridges Benjamin H. T. , Dolan Erin L.
Published: August 2023

Here we present the development and initial validation of the Mentoring in Undergraduate Research Survey (MURS) as a measure of a range of mentoring experienced by undergraduate science researchers. We drafted items based on qualitative research and refined the items through cognitive interviews and expert sorting. We used national dataset to evaluate the internal structure of the measure and a second national dataset to examine how responses on the MURS related to theoretically-relevant constructs and student characteristics. Our factor analytic results indicate seven lower order forms of mentoring experiences: abusive supervision, accessibility, career and technical support, psychosocial support, interpersonal mismatch, sexual harassment, and unfair treatment. These forms of mentoring mapped onto two higher-order factors: supportive and destructive mentoring experiences. Although most undergraduates reported experiencing supportive mentoring, some reported experiencing absence of supportive as well as destructive experiences. Undergraduates who experienced less supportive and more destructive mentoring also experienced lower scientific integration and a dampening of their beliefs about the value of research. The MURS should be useful for investigating the effects of mentoring experienced by undergraduate researchers and for testing interventions aimed at fostering supportive experiences and reducing or preventing destructive experiences and their impacts.

Highlight summary

This study presents the development and initial validation of the Mentoring in Undergraduate Research Survey, including evidence of its internal structure as well as convergent, discriminant, and predictive validity.
Coxsackievirus infection induces direct pancreatic β-cell killing but poor anti-viral CD8+ T-cell responses
Authors: Vecchio Federica , Carré Alexia , Korenkov Daniil , Zhou Zhicheng , Apaolaza Paola , Tuomela Soile , Burgos-Morales Orlando , Snowhite Isaac , Perez-Hernandez Javier , Brandao Barbara , Afonso Georgia , Halliez Clémentine , Kaddis John , Kent Sally C. , Nakayama Maki , Richardson Sarah J. , Vinh Joelle , Verdier Yann , Laiho Jutta , Scharfmann Raphael , Solimena Michele , Marinicova Zuzana , Bismuth Elise , Lucidarme Nadine , Sanchez Janine , Bustamante Carmen , Gomez Patricia , Buus Soren ,   the nPOD-Virus Working Group, You Sylvaine , Pugliese Alberto , Hyoty Heikki , Rodriguez-Calvo Teresa , Flodstrom-Tullberg Malin , Mallone Roberto
Published: August 2023

Coxsackievirus B (CVB) infection of pancreatic β cells is associated with β-cell autoimmunity. We investigated how CVB impacts human β cells and anti-CVB T-cell responses. β cells were efficiently infected by CVBin vitro, downregulated HLA Class I and presented few, selected HLA-bound viral peptides. Circulating CD8+T cells from CVB-seropositive individuals recognized only a fraction of these peptides, and only another sub-fraction was targeted by effector/memory T cells that expressed the exhaustion marker PD-1. T cells recognizing a CVB epitope cross-reacted with the β-cell antigen GAD. Infected β cells, which formed filopodia to propagate infection, were more efficiently killed by CVB than by CVB-reactive T cells. Thus, ourin-vitroandex-vivodata highlight limited T-cell responses to CVB, supporting the rationale for CVB vaccination trials for type 1 diabetes prevention. CD8+T cells recognizing structural and non-structural CVB epitopes provide biomarkers to differentially follow response to infection and vaccination.
Plasticity of circadian and circatidal rhythms in activity and transcriptomic dynamics in a freshwater snail
Authors: Yokomizo Takumi , Takahashi Yuma
Published: August 2023

Organisms have diverse biological clocks synchronized with environmental cycles depending on their habitats. Anticipation of tidal changes has driven the evolution of circatidal rhythms in some marine species. In a freshwater snail,Semisulcospira reiniana, individuals in nontidal areas exhibit circadian rhythms, whereas those in tidal areas exhibit both circadian and circatidal rhythms. We investigated whether the circatidal rhythms are genetically determined or induced by environmental cycles. After exposure to a simulated tidal cycle, both tidal and nontidal populations exhibited circatidal rhythms in locomotive activity. Transcriptome analysis revealed that genes with circatidal oscillation increased due to entrainment to the tidal cycle in both populations and dominant rhythmicity was consistent with the environmental cycle. These results suggest plasticity in the endogenous rhythm in both populations. However, circatidal oscillating genes were more abundant in the tidal population than in the nontidal population, suggesting that a greater number of genes are associated with circatidal clocks in the tidal population compared to the nontidal population. Our findings suggest that the plasticity of biological rhythms and genetic changes in the molecular network between clocks and downstream genes may have contributed to the adaptation to the tidal environment inS. reiniana.
The Cyclophilin Inhibitor Rencofilstat Decreases HCV-induced Hepatocellular Carcinoma Independently of Its Antiviral Activity
Authors: Stauffer Winston , Bobardt Michael , Ure Daren , Foster Robert , Gallay Philippe
Published: August 2023

There is an urgent need for the identification of new drugs that inhibit HCV-induced hepatocellular carcinoma (HCC). Our work demonstrates that cyclophilin inhibitors (CypI) represent such new drugs. We demonstrated that the non-immunosuppressive cyclosporine A (CsA) analog (CsAa) rencofilstat possesses dual therapeutic activities for the treatment of HCV infection and HCV-induced HCC. Specifically, we showed that HCV infection of humanized mice results in the progressive development of HCC. This was true for four genotypes tested (1 to 4). Remarkably, we demonstrated that rencofilstat inhibits the development of HCV-induced HCC in mice even when added 16 weeks post-infection when HCC is well established. Importantly, we showed that rencofilstat drastically reduces HCC progression independently of its anti-HCV activity. Indeed, the CypI rencofilstat inhibits HCC while other anti-HCV agents such as NS5A (NS5Ai) and NS5B (NS5Bi) fail to reduce HCC. In conclusion, this study shows for the first time that the CypI rencofilstat represents a potent therapeutic agent for the treatment of HCV-induced HCC.
Allosteric DNAzyme for sensitive detection of nucleic acids for molecular diagnosis
Authors: Shi Chenzhi , Wang Pengfei
Published: August 2023

Nucleic acids in biofluids are emerging biomarkers for molecular diagnosis of diseases, whose clinical use has been hindered by the lack of sensitive and convenient detection assays. Herein, we report a sensitive nucleic acid detection method based on allosteric DNAzyme biosensors named SPOT (sensitive loop-initiated DNAzyme biosensor for nucleic acid detection) by rationally designing a programmable DNAzyme of endonuclease capability. SPOT can be activated once a nucleic acid target of specific sequence binds to its allosteric module to induce conformational reconfiguration of DNAzyme enabling continuous cleavage of molecular reporters. SPOT provides a highly robust platform for sensitive (LOD: femtomolar for miRNAs, attomolar for SARS-CoV-2 RNA), specific (single-nucleotide discrimination), and convenient (one-step, one-pot, preamplification-free) detection of low-abundant nucleic acid biomarkers. For clinical validation, we demonstrated that SPOT is capable of detecting serum miRNAs (e.g., miR-155, miR-21) from patients for the precise diagnosis of breast cancer, gastric cancer, and prostate cancer. Furthermore, SPOT exhibits potent detection capability over SARS-CoV-2 RNA from clinical swabs with high sensitivity and specificity. Lastly, SPOT is compatible with point-of-care testing modalities such as lateral flow assay to enable convenient visualization. Hence, we envision that SPOT may serve as a robust platform for sensitive detection of a variety of nucleic acid targets towards clinical applications in molecular diagnosis.
Early-onset diabetes in Africa: A mini-review of the current genetic profile
Authors: Adadey Samuel Mawuli , Mensah Joy Afua , Acquah Kojo Sekyi , James Abugri , Osei-Yeboah Richard
Published: August 2023

Early-onset diabetes is poorly diagnosed partly due to its heterogeneity and variable presentations. Although several genes have been associated with the disease, these genes are not well studied in Africa. We sought to identify the major neonatal, early childhood, juvenile, or early-onset diabetes genes in Africa; and evaluate the available molecular methods used for investigating these gene variants. A literature search was conducted on PubMed, Scopus, Africa-Wide Information, and Web of Science databases. The retrieved records were screened and analyzed to identify genetic variants associated with early-onset diabetes. Although 319 records were retrieved, 32 were considered for the current review. Most of these records (22/32) were from North Africa. The disease condition was genetically heterogenous with most cases possessing unique gene variants. We identified 22 genes associated with early-onset diabetes, 9 of which had variants (n=19) classified as pathogenic or likely pathogenic (PLP). Among the PLP variants,IER3IP1: p.(Leu78Pro) was the variant with the highest number of cases. There was limited data from West Africa, hence the contribution of genetic variability to early-onset diabetes in Africa could not be comprehensively evaluated. It is worth mentioning that most studies were focused on natural products as antidiabetics and only a few studies reported on the genetics of the disease.ABCC8andKCNJ11were implicated as major contributors to early-onset diabetes gene networks. Gene ontology analysis of the network associated ion channels, impaired glucose tolerance, and decreased insulin secretions to the disease. Our review highlights 9 genes from which PLP variants have been identified and can be considered for the development of an African diagnostic panel. There is a gap in early-onset diabetes genetic research from sub-Saharan Africa which is much needed to develop a comprehensive, efficient, and cost-effective genetic panel that will be useful in clinical practice on the continent and among the African diasporas.
Acute renal injury in patients with COVID-19, in the critical care unit of a public hospital, Lima-Peru
Authors: Venegas-Justiniano Yanissa , Hurtado-Aréstegui Abdías , Mucho-Vilca Karina
Published: August 2023

Objective

To determine the clinical and laboratory characteristics, as well as evaluating the factors associated with mortality in patients with COVID-19 infection and acute kidney injury (AKI) hospitalized in the Intensive Care Unit (ICU) of the Hospital Nacional Arzobispo Loayza.

Materials and Methods

Retrospective cohort study, with convenience sampling during the period from April 2020 to March 2021, through the review of medical records data. Inclusion criteria were; patients ≥ 18 years old, with a diagnosis of COVID-19 infection, who were admitted to ICU with normal renal function and developed AKI during their stay in ICU. Exclusion criteria were; patients who developed AKI prior to ICU admission, patients with chronic kidney disease with and without dialysis.

Results

A total of 177 medical records that met the inclusion and exclusion criteria were evaluated. The mean age was 57.2±13.2 years, 145 (81.4%) were male; comorbidities were: obesity 112(63.3%), arterial hypertension 55 (31.1%) and diabetes mellitus 30(16.9%); the most frequent cause of AKI was hypoperfusion (93%). 83 participants (46.8%) received dialytic support in the intermittent hemodialysis modality. In-hospital mortality was 151 (85.3%) and was higher in the group with stage 3 AKI: 109 (72.2%). The increase in ferritin level (OR: 10.04 (95%CI 4.4-38.46), p<0.001) and APACHE score (OR: 1.75 (95%CI 1.4-2.12), p<0.001), as well as the decrease in PaO2/FiO2level (OR: 0.85 (95%CI 0.59-0.92), p<0.041, were related to mortality.

Conclusions

AKI in ICU patients with COVID-19 infection has a high mortality and the related factors were the increase in APACHE II score and ferritin level, as well as the decrease in PaO2/FiO2level.
The microbiome of an amphibious plant shifts dramatically across the host life cycle
Authors: Montiel-Molina Jorge A Mandussí , Sexton Jason P , Beman J Michael , Frank A Carolin
Published: August 2023

Interactions between plants and their associated microbiomes are thought to enhance the capacity of the host plant to overcome extreme conditions, yet the significance of microbially mediated stress tolerance in most plant species and ecosystems remains unknown. For the first time, we examined the microbiome of the amphibious plantEryngium castrense(Apiaceae) inhabiting Mediterranean climate ephemeral wetlands in California.Eryngium castrensehas the capacity to survive as both an aquatic and terrestrial plant, thereby living under contrasting extremes of water stress. Whether plant-associated microbial communities are also affected by such changes, and what ecological role they play while inhabiting amphibious plants, is an underexplored topic of plant-microbial interactions in natural and artificial systems. We amplified and sequenced 16S rRNA genes from bacteria and archaea to examine microbial communities associated with roots and shoots over the plants’ full life cycle. We observed that the microbiome changes from the aquatic stage to the terrestrial stage, and that roots and shoots represent distinct habitats within the plant host ecosystem. When compared with soil and water column samples, plant samples retained a unique, differentiated core microbiome. Taxa located in the roots during the terrestrial stage were linked with potential functions such as nitrogen acquisition, sulfur assimilation, and resistance to heavy metals, whereas aquatic roots held potential phythoparasites. Overall, our results provide new insights into symbiotic relationships in plants subject to stress-related to water saturation and deficiency.
Improved modeling of RNA-binding protein motifs in an interpretable neural model of RNA splicing
Authors: Gupta Kavi , Yang Chenxi , McCue Kayla , Bastani Osbert , Sharp Phillip A , Burge Christopher B , Solar-Lezama Armando
Published: August 2023

Sequence-specific RNA-binding proteins (RBPs) play central roles in splicing decisions, but their exact binding locations and activities are difficult to predict. Here, we describe a modular splicing architecture that leveragesin vitro-derived RNA affinity models for 79 human RBPs and the annotated human genome to produce improved models of RBP binding and activity. Binding and activity are modeled by separate Motif and Aggregator components that can be mixed and matched, enforcing sparsity to improve interpretability. Standard affinity models yielded reasonable predictions, but substantial improvements resulted from using a new Adjusted Motif (AM) architecture. While maintaining accurate modeling of in vitro binding, training these AMs on the splicing task yielded improved predictions of binding sitesin vivoand of splicing activity, using independent crosslinking and massively parallel splicing reporter assay data. The modular structure of our model enables improved generalizability to other species (insects, plants) and to exons of different evolutionary ages.
Effects of phosphorylation on Drp1 activation by its receptors, actin, and cardiolipin
Authors: Liu Ao , Hatch Anna L. , Higgs Henry N.
Published: August 2023

Drp1 is a dynamin family GTPase that is required for mitochondrial and peroxisomal division, in which it oligomerizes into a ring and constricts the underlying membrane in a GTP hydrolysis-dependent manner. Oligomerization increases Drp1 GTPase activity through interactions between neighboring GTPase domains. In cells, Drp1 is regulated by several factors including Drp1 receptors, actin filaments, cardiolipin, and phosphorylation at two sites: S579 and S600. Phosphorylation of S579 is widely regarded as activating, while S600 phosphorylation is commonly considered inhibiting. However, the direct effects of phosphorylation on Drp1 GTPase activity have not been investigated in detail. In this study, we compare the effects of S579 and S600 phosphorylation on purified Drp1, using phospho-mimetic mutants andin vitrophosphorylation. The oligomerization state of both phospho-mimetic mutants is shifted toward smaller oligomers. Both phospho-mimetic mutations maintain basal GTPase activity, but eliminate GTPase stimulation by actin and decrease GTPase stimulation by cardiolipin, Mff, and MiD49. Phosphorylation of S579 by Erk2 produces similar effects. When mixed with wild-type Drp1, both S579D and S600D phospho-mimetic mutants reduce the actin-stimulated GTPase activity of Drp1-WT. Conversely, a Drp1 mutant that lacks GTPase activity, the K38A mutant, stimulates Drp1-WT GTPase activity under both basal and actin-stimulated conditions, similar to previous results for dynamin-1. These results suggest that the effect of S579 phosphorylation is not to activate Drp1 directly, and likely requires additional factors for stimulation of mitochondrial fission in cells. In addition, our results suggest that nearest neighbor interactions within the Drp1 oligomer affect catalytic activity.
SAW: An efficient and accurate data analysis workflow for Stereo-seq spatial transcriptomics
Authors: Gong Chun , Li Shengkang , Wang Leying , Zhao Fuxiang , Fang Shuangsang , Yuan Dong , Zhao Zijian , He Qiqi , Li Mei , Liu Weiqing , Li Zhaoxun , Xie Hongqing , Liao Sha , Chen Ao , Zhang Yong , Li Yuxiang , Xu Xun
Published: August 2023

The basic analysis steps of spatial transcriptomics involve obtaining gene expression information from both space and cells. This process requires a set of tools to be completed, and existing tools face performance issues when dealing with large data sets. These issues include computationally intensive spatial localization, RNA genome alignment, and excessive memory usage in large chip scenarios. These problems affect the applicability and efficiency of the process. To address these issues, a high-performance and accurate spatial transcriptomics data analysis workflow called Stereo-Seq Analysis Workflow (SAW) has been developed for the Stereo-Seq technology developed by BGI. This workflow includes mRNA spatial position reconstruction, genome alignment, gene expression matrix generation and clustering, and generate results files in a universal format for subsequent personalized analysis. The excutation time for the entire analysis process is ∼148 minutes on 1G reads 1*1 cm chip test data, 1.8 times faster than unoptimized workflow.
Effects of the COVID-19 lockdowns on the care delivery to the children with autism spectrum disorder: a web-based cross-sectional study
Authors: Mirahmadizadeh Alireza , Heiran Alireza , Nemati Hamid , Aminnia Shiva , Azadian Fatemeh , Rezaei Fatemeh , Sahebi Roya , Miyar Ata , Sharifi Mohammad Hossein , Tavasoli Mojgan
Published: August 2023

Purpose

Children and adolescents with autism spectrum disorder need special attention for their mental and physical health and education. This study aims to investigate the effects of the COVID-19 pandemic on them.

Design/methodology/approach

This descriptive cross-sectional study was conducted on data collected from an online survey. Respondents were the parents or caregivers of autistic children aged 3–18. It measured opinions about the favorable and unfavorable behavioral changes related to their children during the COVID-19 lockdowns.

Findings

In total, 131 respondents participated in the study. The mean age of their autistic children was 11.45 ± 4.26 years, of whom 78% were boys. Improved good behaviors during lockdowns included interaction with parents and siblings, eating healthy foods, quality of sleep, eye contact, pointing and asking for something, imitating sounds and phrases, sharing interests, reaction to emotions and empathy with family members, but sleep hours decreased.

Originality/value

Lockdown provided opportunities for examining the behaviors of children with autism taking into account its favorable and unfavorable effects, to improve communicating and behaving with these children.
Environmental concerns in brand love and hate: an emerging market’s purview of masstige consumers
Authors: Singh Swati , Wagner Ralf
Published: August 2023

Purpose

Fashion brands are one of the strongest means of expressing consumers identity. This study explores and empirically validates the concepts of brand love and hate for masstige fashion brands from the purview of emerging markets. This study deciphers three components of masstige fashion brand promise through the lens of hedonic identity, uniqueness and expected social gains for the affluent middle-class consumers. The model is complemented by the impact of environmental and society’s well-being.

Design/methodology/approach

Empirical evidence was obtained through an online survey in India. Total of 222 complete responses were used to test hypotheses by fitting a model with the partial least squares algorithm.

Findings

Fashion brand love is triggered by consumers’ hedonic identity and expected social gains. Brand hate is fuelled by environmental and societal well-being concerns, expected social gains and uniqueness. Theoretical contribution is threefold: First, the relevance of social and environmental consequences reflecting consumers’ accepted responsibility for their masstige consumption is introduced. Second, the study deciphers the emotions related to masstige brand love and brand hate for emerging market’s affluent middle-class. Third, empirical results contribute to the ongoing discussion on whether brand hate and love are two distinct concepts or collapse to be two extremes of one and the same continuum.

Practical implications

Middle-class consumers in India are strict in their avoidance and rejection of the lower classes’ preferred fashion brands. Targeting must consider the social classes hierarchy. Marketing-mix design, particularly prices and distribution networks, need to enable a distinction between the social classes.

Social implications

Masstige fashion brand love and hate turn out to be two distinct constructs that co-exist rather than being two extremes of one and the same dimension.

Originality/value

Indian middle-class consumers satisfy their need of environmental and social caretaking by avoidance and brand hate but continue to choose masstige brands to demonstrate social status and are not modernizing their traditional accumulative materialism.