bluuebunny/crossref_metadata_2025 huggingface dataset:
Maternal behavior influences vocal practice and learning processes in the greater sac-winged bat
Authors: Fernandez Ahana A. , Serve Nora , Fabian Sarah-Cecil , Knörnschild Mirjam
Published: May 2024

Learning, particularly vocal learning, is often a social process. In human infants, it is well-established that social interactions influence speech acquisition and are hypothesized to modulate attentiveness and sensory processes, thereby affecting the speech-learning process. However, our understanding of how social interactions shape vocal ontogenetic processes in non-human mammals, particularly those which vocally learn, remains limited. In the batSaccopteryx bilineata, pups acquire the adult vocal repertoire through a distinctive babbling behavior that shows interesting similarities to human infant babbling. While babbling encompasses many different syllable types, it is particularly noteworthy that pups learn song syllables by imitating adult singing males. The pups’ social environment involves frequent interactions with their mothers, whereas adult males mainly serve as the primary source of acoustic input. We monitored the vocal ontogeny of wild pups, investigating whether their social environment influenced three aspects of babbling: the amount of vocal practice, the pups’ final syllable repertoire size and the production of the syllable types acquired through vocal learning. The results demonstrate that maternal behavioral displays significantly influence the amount of vocal practice, the presence and versatility of song syllable types in babbling and the percentage of mature song syllables. Our findings show that maternal feedback plays a significant role in the vocal ontogeny and learning processes ofS. bilineata, thus enhancing our understanding of the relationship between social feedback and vocal development in mammalian vocal learners.
Benchmarking 13 tools for mutational signature attribution, including a new and improved algorithm
Authors: Jiang Nanhai , Wu Yang , Rozen Steven G.
Published: May 2024

Mutational signatures are characteristic patterns of mutations caused by endogenous mutational processes or by exogenous mutational exposures. There has been little benchmarking of approaches for determining which signatures are present in a sample and estimating the number of mutations due to each signature. This problem is referred to as “signature attribution”. We show that there are often many combinations of signatures that can reconstruct the patterns of mutations in a sample reasonably well, even after encouraging sparse solutions. We benchmarked thirteen approaches to signature attribution, including a new approach called Presence Attribute Signature Activity (PASA), on large synthetic data sets (2,700 synthetic samples in total). These data sets recapitulated the single-base, insertion-deletion, and doublet-base mutational signature repertoires of 9 cancer types. For single-base substitution mutations, PASA and MuSiCal outperformed other approaches on all the cancer types combined. However, the ranking of approaches varied by cancer type. For doublet-base substitutions and small insertions and deletions, while PASA outperformed the other approaches in most of the nine cancer types, the ranking of approaches again varied by cancer type. We believe this variation reflects inherent difficulties in signature attribution. These difficulties stem from the fact that there are often many attributions that can reasonably explain the pattern of mutations in a sample and from the combinatorial search space due to the need to impose sparsity. Tables herein can provide guidance on the selection of mutational signature attribution approaches that are best suited to particular cancer types and study objectives.
Pleiotropy and Disease Interactors: The Dual Nature of Genes Linking Ageing and Ageing-related Diseases
Authors: Vega Magdaleno Gustavo Daniel , de Magalhaes Joao Pedro
Published: May 2024

Ageing-related diseases (ARDs) exhibit a broad spectrum of phenotypes yet consistently increase in incidence with advancing age. This suggests that, despite their diversity, ARDs could potentially share common biological processes deeply rooted in the mechanisms of ageing, presenting opportunities for unified therapeutic strategies. Using a network approach, we analysed gene proximity to 52 ARDs from the UK Biobank, integrating with protein-protein interaction (PPI), gene coexpression, KEGG pathways, and ageing-related genes. Interestingly, while most ageing-related genes did not associate with ARDs, they were closer to multiple ARDs than random genes. This was mainly due to indirect connections to diverse Communities of ARDs (ARCs), what we calliARC-Interactors, implying indirect association to multiple ARDs through interaction with ARD-related genes, primarily via PPI and KEGG. Genes that are associated with multiple ARCs,i.e.,Pleiotropicgenes, were predominantly related to immunological disorders. We found a polarizing effect. When compared to multiple ageing- and disease-related genes, highPleiotropicgenes showed the highest tissue specificity and lowest coexpression with themselves and other diseases. In contrast, high iARC-interactivegenes (as those of ageing) significantly displayed the exact opposite effects, suggesting two mechanisms for genes to affect multiple ARDs, one operating through modulatory genes that simultaneously affect numerous tissues and processes; and another rather specialised, affecting single tissues that are widespread across the body, as potentially occurring in autoimmune diseases. Lastly, we used Machine Learning (ML) to predict potentially novel ageing-related genes based on each network’siARC-Interactionsand genes’ proximity to ARDs. PPI and KEGG showed the best performance with their top candidate genes enriched for regulation of protein metabolic process, protein stabilization, positive regulation of developmental process, and cellular response to chemical stimulus. This work paints a deeper picture of the multiple types of interactions between ageing-related processes and ARDs.
Pervasive ancestry bias in variant effect predictors
Authors: Pathak Ankit K. , Bora Nikita , Badonyi Mihaly , Livesey Benjamin J. ,   SG10K_Health Consortium, Ngeow Joanne , Marsh Joseph A.
Published: May 2024

Computational variant effect predictors (VEPs) are playing increasingly important roles in the interpretation of human genetic variants. We observe striking differences in the ways that many VEPs score variants from European compared to non-European populations. We advocate for the adoption of population-free VEPs, i.e. those not trained on human population or clinical variants, to improve health equity and enhance the accuracy of genetic diagnoses across diverse populations.
Impact of liver-specific survival motor neuron (SMN) depletion on central nervous system and peripheral tissue pathology
Authors: de Almeida Monique Marylin Alves , De Repentigny Yves , Gagnon Sabrina , Sutton Emma R. , Kothary Rashmi
Published: May 2024

Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder stemming from deletions or mutations in the Survival Motor Neuron 1 (SMN1) gene, leading to decreased levels of SMN protein, and subsequent motor neuron death and muscle atrophy. While traditionally viewed as a disorder predominantly affecting motor neurons, recent research suggests the involvement of various peripheral organs in SMA pathology. Notably, the liver has emerged as a significant focus due to the observed fatty liver phenotype and dysfunction in both SMA mouse models and SMA patients. Despite these findings, it remains unclear whether intrinsic depletion of SMN protein in the liver contributes to pathology in the peripheral or central nervous systems. To address this knowledge gap, we developed a mouse model with a liver-specific depletion of SMN by utilizing anAlb-Cretransgene together with oneSmn2Ballele and oneSmnexon 7 allele flanked by loxP sites. Initially, we evaluated phenotypic changes in these mice at postnatal day 19 (P19), a time when the severe model of SMA, theSmn2B/-mice, typically exhibit many symptoms of the disease. Our findings indicate that liver-specific SMN depletion does not induce motor neuron death, neuromuscular pathology or muscle atrophy, characteristics typically observed in theSmn2B/-mouse at P19. However, mild liver steatosis was observed at this time point, although no changes in liver function were detected. Notably, pancreatic alterations resembled that ofSmn2B/-mice, with a decrease in insulin-producing β-cells and an increase in glucagon-producing α-cells, accompanied by a reduction in blood glucose and an increase in plasma glucagon and glucagon-like peptide (GLP-1) levels. Moreover, these changes were transient, as P60 mice exhibited recovery of liver and pancreatic function. While the mosaic pattern of the Cre-mediated excision precludes definitive conclusions regarding the contribution of liver-specific SMN depletion to overall tissue pathology, our findings highlight an intricate connection between liver function and pancreatic abnormalities in SMA, adding a nuanced layer to our understanding of the disease’s complexities.
Characteristics of JN.1-derived SARS-CoV-2 subvariants SLip, FLiRT, and KP.2 in neutralization escape, infectivity and membrane fusion
Authors: Li Pei , Faraone Julia N. , Hsu Cheng Chih , Chamblee Michelle , Zheng Yi-Min , Carlin Claire , Bednash Joseph S. , Horowitz Jeffrey C. , Mallampalli Rama K. , Saif Linda J. , Oltz Eugene M. , Jones Daniel , Li Jianrong , Gumina Richard J. , Xu Kai , Liu Shan-Lu
Published: May 2024

SARS-CoV-2 variants derived from the immune evasive JN.1 are on the rise worldwide. Here, we investigated JN.1-derived subvariants SLip, FLiRT, and KP.2 for their ability to be neutralized by antibodies in bivalent-vaccinated human sera, XBB.1.5 monovalent-vaccinated hamster sera, sera from people infected during the BA.2.86/JN.1 wave, and class III monoclonal antibody (Mab) S309. We found that compared to parental JN.1, SLip and KP.2, and especially FLiRT, exhibit increased resistance to COVID-19 bivalent-vaccinated human sera and BA.2.86/JN.1-wave convalescent sera. Interestingly, antibodies in XBB.1.5 monovalent vaccinated hamster sera robustly neutralized FLiRT and KP.2 but had reduced efficiency for SLip. These JN.1 subvariants were resistant to neutralization by Mab S309. In addition, we investigated aspects of spike protein biology including infectivity, cell-cell fusion and processing, and found that these subvariants, especially SLip, had a decreased infectivity and membrane fusion relative to JN.1, correlating with decreased spike processing. Homology modeling revealed that L455S and F456L mutations in SLip reduced local hydrophobicity in the spike and hence its binding to ACE2. In contrast, the additional R346T mutation in FLiRT and KP.2 strengthened conformational support of the receptor-binding motif, thus counteracting the effects of L455S and F456L. These three mutations, alongside D339H, which is present in all JN.1 sublineages, alter the epitopes targeted by therapeutic Mabs, including class I and class III S309, explaining their reduced sensitivity to neutralization by sera and S309. Together, our findings provide insight into neutralization resistance of newly emerged JN.1 subvariants and suggest that future vaccine formulations should consider JN.1 spike as immunogen, although the current XBB.1.5 monovalent vaccine could still offer adequate protection.
Systematic analysis of gut bacterial carcinogen metabolism and its functional consequences
Authors: Zhang Boyao , Maftei George-Eugen , Bartmanski Bartosz , Zimmermann Michael
Published: May 2024

Organic carcinogens, in particular DNA-reactive compounds, contribute to the irreversible initiation step of tumorigenesis through introduction of genomic instability. Although carcinogen bioactivation and detoxification by human enzymes has been extensively studied, carcinogen biotransformation by human-associated bacteria, the microbiota, has not yet been systematically investigated. We tested the biotransformation of 68 mutagenic carcinogens by 34 bacterial species representative for the upper and lower human gastrointestinal tract and found that the majority (41) of the tested carcinogens undergo bacterial biotransformation. To assess the functional consequences of microbial carcinogen metabolism, we developed a pipeline to couple gut bacterial carcinogen biotransformation assays with Ames mutagenicity testing and liver biotransformation experiments. This revealed a bidirectional crosstalk between gut microbiota and host carcinogen metabolism, which we validated in gnotobiotic mouse models. Overall, the systematic assessment of gut microbiota carcinogen biotransformation and its interplay with host metabolism highlights the gut microbiome as an important modulator of exposome-induced tumorigenesis.
The role of affect regulation and mentalizing in mediating the attachment-epistemic trust relationship. Differences between junior and senior students…Who is at risk?
Authors: Karagiannopoulou Evangelia , Lianos Panagiotis , Andriopoulou Panoraia , Rentzios Christos , Fonagy Peter
Published: May 2024

Research on emotional factors and mental health in higher education has gained traction. Much attention has focused on first-year students as a potentially at-risk group, though some studies suggest that all students might face similar risks. This study examines differences between junior and senior undergraduates in terms of mentalizing, emotion regulation (ER), and psychological mindedness. These constructs relate to understanding one’s own and others’ mental states, potentially mediating the relationship between attachment and epistemic trust (ET). The current study includes 460 undergraduate students, most of whom are female (96%). Results show that senior students score higher on reappraisal, certainty, and interest/curiosity compared to junior students. However, these factors did not mediate the relationship between anxious attachment orientation and ET. Certainty and interest/curiosity mediated the relationship between avoidant attachment orientation and ET, suggesting similar mediation patterns for junior and senior students. On the other hand, suppression and uncertainty/confusion were critical mediators in the relationship between insecure (anxious and avoidant) attachment orientations and epistemic trust. These findings are discussed within the framework of attachment and mentalizing literature, along with relevant connections to educational studies.
Victimization Status Among Persons with Disabilities and its Predictors: Evidence from Bangladesh National Survey on Persons with Disabilities
Authors: Rahman Mizanur , Rana Md Shohel , Khandaker Gulam , Rahman Md Mostafizur , Khan Md Nuruzzaman
Published: May 2024

Background

Persons with disabilities often face various forms of victimization, yet there is limited research exploring this phenomenon in Bangladesh. This study aims to investigate the victimization status among persons with disabilities and identify its predictors.

Methods

Data of 4293 persons with disabilities analyzed in this study were extracted from the 2021 National Survey on Persons with Disabilities. Victimization status (yes, no) was considered as the outcome variables. Explanatory variables considered were factors at the individual, household, and community levels. A multilevel mixed-effect logistic regression model was used to explore the association of the outcome variable with explanatory variables by dividing the total sample into age groups of 0-17 years and ≥ 18 years.

Results

The study found that 44% of persons with disabilities in Bangladesh experienced victimization, predominantly involving neighbours (90.64%), friends (28.41%), and family members (27.07%). Among persons aged 0-17 years, increasing age was associated with higher likelihood of being victimized, while residing in the richest households or certain divisions like Khulna and Rangpur was associated with lower likelihoods. Conversely, among respondents aged 18-95 years, increasing age was associated with lower likelihood of being victimized. Unmarried respondents had increased likelihood of victimization compared to married individuals. Furthermore, persons residing in the richest wealth quintile compared to the poorest, and residence in certain divisions such as Chattogram, Khulna, Mymensingh, Rangpur, and Sylhet reported higher likelihoods of victimization compared to those in the Barishal division.

Conclusion

This study’s findings underscore that around 4 in 10 persons with disabilities are being victimized. Tailored programs and awareness-building initiatives covering neighbours, friends, and family members of persons with disabilities are important to ensure dignified lives for this population.
Higher frequency of interstate over international transmission chains of SARS-CoV-2 virus at the Rio Grande do Sul - Brazil state borders
Authors: Dezordi Filipe Zimmer , Silva Junior José Valter Joaquim , Ruoso Terimar Facin , Batista Angela Giovana , Fonseca Pedro Mesquita , Salvato Richard Steiner , Gregianini Tatiana Schäffer , Lopes Thaísa Regina Rocha , Flores Eduardo Furtado , Weiblen Rudi , Brites Patricia Chaves , Silva Mônica de Medeiros , da Rocha João Batista Teixeira , Barbosa Gustavo de Lima , Machado Lais Ceschini , da Silva Alexandre Freitas , Paiva Marcelo Henrique Santos , Bezerra Matheus Filguera , Campos Tulio de Lima , Gräf Tiago , Sganzerla Daniel Angelo , Loreto Elgion Lucio da Silva , Wallau Gabriel da Luz
Published: May 2024

Brazil's COVID-19 response has faced challenges due to the continuous emergence of variants of concern (VOCs), emphasizing the need for ongoing genomic surveillance and retrospective analyses of past epidemic waves. Rio Grande do Sul (RS), Brazil's southernmost state, has crucial international borders and trades with Argentina and Uruguay, along with significant domestic connections. The source and sink of transmission with both national and international hubs raises questions about the RS role in the transmission of the virus, which has not been fully explored. Nasopharyngeal samples from various municipalities in RS were collected between June 2020 and July 2022. SARS-CoV-2 whole genome amplification and sequencing were performed using high-throughput Illumina sequencing. Bioinformatics analysis encompassed the development of scripts and tools to take into account epidemiological information to reduce sequencing disparities bias among the regions/countries, genome assembly, and large-scale phylogenetic reconstruction. Here, we sequenced 1,480 SARS-CoV-2 genomes from RS, covering all major regions. Sequences predominantly represented Gamma (April-June 2021) and Omicron (January-July 2022) variants. Phylogenetic analysis revealed a regional pattern for transmission dynamics, particularly with Southeast Brazil for Gamma, and a range of inter-regional connections for Delta and Omicron within the country. On the other hand, international and cross-border transmission with Argentina and Uruguay was rather limited. We evaluated the three VOCs circulation over two years in RS using a new subsampling strategy based on the number of cases in each state during the circulation of each VOC. In summary, the retrospective analysis of genomic surveillance data demonstrated that virus transmission was less intense between country borders than within the country. These findings suggest that while non-pharmacological interventions were effective to mitigate transmission across international land borders in RS, they were unsuficient to contain transmission at the domestic level.
Use of tobacco and nicotine products among adolescents in Sub-Saharan Africa: protocol for a population-based multi-country household survey
Authors: Kisia Lyagamula , Mohamed Shukri F , Kyule Grace , Tchoupé Christelle , Abolarin Olatunbosun , Pokothoane Retselisitsoe , Agerfa Terefe Gelibo , Iddi Samuel , Okumu Boscow , Mbaya Nelson , Kadengye Damazo T , Mdege Noreen Dadirai
Published: May 2024

Background

The use of tobacco among adolescents in low- and middle-income countries, is a public health issue of concern. The tobacco industry’s aggressive marketing tactics target young people in African countries, leading to early initiation of tobacco use. While existing evidence focuses on 13-15-year-olds, data from Sub-Saharan Africa indicates that smoking initiation ranges from as young as 7 years old to around 16 years old. The lack of data on adolescent tobacco use in African countries limits policymakers’ ability to implement evidence-based tobacco control policies. This study aims to address the critical lack of quality and timely primary data on adolescent tobacco use thereby enhancing the country’s capacity to target interventions effectively, engage local governments, and attract global attention and funding for adolescent health initiatives.

Methods

We will conduct a cross-sectional nationwide survey among adolescents aged 10 - 17 years in urban and rural areas of the Democratic Republic of Congo (DRC), Kenya and Nigeria. This household-based survey will utilise a multi-stage stratified sample design to ensure representation across diverse geographic and demographic characteristics.

Discussion

Through this initiative, we aim to catalyse action at national and international levels to combat the tobacco epidemic among adolescents in SSA. The findings from the DaYTA study will empower stakeholders to advocate for effective tobacco control measures, promote adolescent health, and safeguard future generations from the harmful effects of tobacco use.
Global and regional associations of enteric infections and asthma
Authors: Ni Duan , Nanan Ralph
Published: May 2024

Asthma is one of the most common chronic diseases globally. There are various risk factors for asthma, including respiratory infections, like rhinovirus and respiratory syncytial virus infections. Nevertheless, impacts from non-respiratory tract infections on asthma remain unresolved. Globally, enteric infections are the most common infections. Their target organ, the intestinal system, shares the same embryonic origin, the endoderm, as the respiratory tract. These led us to inspect the potential associations between enteric infections and asthma.

We analyzed three independent epidemiological datasets with the cutting-edge generalized additive model (GAM). Consistently, in two regional datasets (America and Japan) and a global dataset, we found that enteric infection incidence was generally linked to increased asthma disease burden.

This is the first study to our knowledge to comprehensively elucidate the positive associations between enteric infections and asthma. Our findings would be instructive to both clinical practice and mechanistic study for asthma.
Knowledge, attitude and utilization of nursing theories among nursing personnel: A descriptive cross-sectional study
Authors: Joseph Joyce , Tom Linnet Maria , Maji Krishna , Sahu Kusumlata , Gupta Lakshmi , Bajpai KM Akriti , Kaur Komalpreet
Published: May 2024

Aim

To assess knowledge, attitude and utilization of Nursing Theories among Nursing Personnel working in a tertiary care centre in India.

Methods

A descriptive cross-sectional study was conducted using a proportionate stratified random sample of 350 nursing personnel in a tertiary care centre in east-central India. A self-structured tool to assess knowledge, practice and utilization was distributed to nursing personnel via Google forms between, March 2024-April 2024.

Results

The results revealed that the mean scores for the knowledge, attitude, and utilization component being 2.58 ± 0.570, 53.64 ± 6.433, and 1.87 ± 0.740, respectively. Among the nursing personnel, the analysis does not show any significant (p-value > 0.05) difference in the mean scores of knowledge, attitude and utilization when comparing different designations, age groups, genders, levels of work experience, professional qualifications, and types of institutes, indicating that the observed differences could be due to chance. However, in utilization, when examining the nature of the job, a significant difference is observed.

Conclusions

It is important to practice nursing theories in clinical setting for better patient care. Theories of nursing contribute to richness of the profession and provide an identity to the profession. Barriers in implementing nursing theories in practice must be examined and a particular focus to be given.
Association of computed tomography scan–assessed body composition with immune and PI3K/AKT pathway proteins in distinct breast cancer tumor components
Authors: Cheng Ting-Yuan David , Fu Dongtao Ann , Falzarano Sara M , Zhang Runzhi , Datta Susmita , Zhang Weizhou , Omilian Angela R. , Aduse-Poku Livingstone , Bian Jiang , Irianto Jarome , Asirvatham Jaya Ruth , Campbell-Thompson Martha
Published: May 2024

This hypothesis-generating study aims to examine the extent to which computed tomography-assessed body composition phenotypes are associated with immune and PI3K/AKT signaling pathways in breast tumors. A total of 52 patients with newly diagnosed breast cancer were classified into four body composition types: adequate (lowest two tertiles of total adipose tissue [TAT]) and highest two tertiles of total skeletal muscle [TSM] areas); high adiposity (highest tertile of TAT and highest two tertiles of TSM); low muscle (lowest tertile of TSM and lowest two tertiles of TAT); and high adiposity with low muscle (highest tertile of TAT and lowest tertile of TSM). Immune and PI3K/AKT pathway proteins were profiled in tumor epithelium and the leukocyte-enriched stromal microenvironment using GeoMx (NanoString). Linear mixed models were used to compare log2-transformed protein levels. Compared with the normal type, the low muscle type was associated with higher expression of INPP4B (log2-fold change = 1.14, p = 0.0003, false discovery rate = 0.028). Other significant associations included low muscle type with increased CTLA4 and decreased pan-AKT expression in tumor epithelium, and high adiposity with increased CD3, CD8, CD20, and CD45RO expression in stroma (P<0.05; false discovery rate >0.2). With confirmation, body composition can be associated with signaling pathways in distinct components of breast tumors, highlighting the potential utility of body composition in informing tumor biology and therapy efficacies.
Rare genetic coding variants associated with age-related episodic memory decline implicate distinct memory pathologies in the hippocampus
Authors: Ali Amanat , Milman Sofiya , Weiss Erica F. , Gao Tina , Napolioni Valerio , Barzilai Nir , Zhang Zhengdong D. , Lin Jhih-Rong
Published: May 2024

Background

Approximately 40% of people aged 65 or older experience memory loss, particularly in episodic memory. Identifying the genetic basis of episodic memory decline is crucial for uncovering its underlying causes.

Methods

We investigated common and rare genetic variants associated with episodic memory decline in 742 (632 for rare variants) Ashkenazi Jewish individuals (mean age 75) from the LonGenity study. All-atom MD simulations were performed to uncover mechanistic insights underlying rare variants associated with episodic memory decline.

Results

In addition to the common polygenic risk of Alzheimer’s Disease (AD), we identified and replicated rare variant association inITSN1andCRHR2. Structural analyses revealed distinct memory pathologies mediated by interfacial rare coding variants such as impaired receptor activation of corticotropin releasing hormone and dysregulated L-serine synthesis.

Discussion

Our study uncovers novel risk loci for episodic memory decline. The identified underlying mechanisms point toward heterogeneous memory pathologies mediated by rare coding variants.
The Effect of Perceived Social support on Cervical Cancer Screening among Nepali women residing in Dhulikhel and Banepa municipality
Authors: Cruanes Gaël , Paudel Pratiksha , Regmi Urja , House Darlene R , Shrestha Archana , Paneru Bandana
Published: May 2024

Background

Cervical cancer ranks as the most common cancer among Nepalese women with a high incidence and mortality. Despite evidence that effective screening programs reduce disease burden, screening services are under-utilized. In various other countries, perceived social support has been shown to increase cervical cancer screening uptake among women.

Objectives

This study assessed the association between perceived social support and cervical cancer screening uptake among women residing in semi-urban areas of Kavrepalanchok district (Dhulikhel and Banepa), Nepal.

Methods

We conducted a cross-sectional study among women aged 30-60 years using telephone interview method from 15thJune to 15thOctober 2021. A validated Multidimensional Scale of Perceived Social Support (MSPSS) was utilized to measure perceived social support. We obtained information on cervical cancer screening uptake through self-reported responses. A Mann Whitney analysis was performed to assess the association between perceived social support and cervical cancer screening uptake.

Results

Four hundred twenty-six women participated in the study. There was a significant association between significant others’ social support (p-value=0.007, 95% CI: 0.08-0.53) and family social support (p-value=0.04, 95% CI: 0.003-0.4).

Conclusion

Women residing in semi-urban areas of Nepal who had higher perceived social support from their significant other and family were more likely to have been screened for cervical cancer. Community interventions fostering conversations about reproductive health between husbands and their wives may increase perceived social support and contribute to higher uptake of cervical cancer screening.
Safe Injection Self-Efficacy is associated with HCV and HIV seropositivity among people who inject drugs in the San Diego-Tijuana border region
Authors: Bailey Katie , Abramovitz Daniela , Rangel Gudelia , Harvey-Vera Alicia , Vera Carlos F. , Patterson Thomas L. , Sánchez-Lira Jaime Arredondo , Davidson Peter J. , Garfein Richard S. , Smith Laramie R. , Pitpitan Eileen V. , Goldenberg Shira M. , Strathdee Steffanie A.
Published: May 2024

Background

Safe injection self-efficacy (SISE) is negatively associated with injection risk behaviors among people who inject drugs (PWID) but has not been examined in differing risk environments. We compared responses to a validated SISE scale between PWID in San Diego, California and Tijuana, Mexico, and examine correlates of SISE among PWID in Tijuana.

Methods

PWID were recruited via street outreach for a longitudinal cohort study from October 2020 – September 2021. We compared SISE scale items by city. Due to low variability in SISE scores among San Diego residents, we restricted analysis of factors associated with SISE to Tijuana residents and identified correlates of SISE scores (low, medium, high) using ordinal logistic regression.

Results

Of 474 participants, most were male (74%), Latinx (78%) and Tijuana residents (73%). Mean age was 44. Mean SISE scores among San Diego residents were high (3.46 of 4 maximum) relative to Tijuana residents (mean: 1.93). Among Tijuana residents, White race and having previously resided in San Diego were associated with higher SISE scores. HCV and HIV seropositivity, homelessness, fentanyl use, polysubstance co-injection, and greater injection frequency were associated with lower SISE scores.

Conclusions

We found profound inequalities between Tijuana and San Diego SISE, likely attributable to differential risk environments. Associations with fentanyl and polysubstance co-injection, injection frequency, and both HIV and HCV seropositivity suggest that SISE contribute to blood-borne infection transmission risks in Tijuana. SISE reflects an actionable intervention target to reduce injection risk behaviors, but structural interventions are required to intervene upon the risk environment.
Prevalence of Diabetes and Prediabetes in Peru: A Systematic Review and Meta-Analysis
Authors: Vera-Ponce Víctor Juan , Zuzunaga-Montoya Fiorella E. , Vásquez-Romero Luisa Erika Milagros , Loayza-Castro Joan A. , Vigil-Ventura Enrique , Ramos Willy
Published: May 2024

Introduction

Diabetes mellitus (DM) and prediabetes represent significant public health challenges in Peru, with prevalence rates showing considerable variation in recent studies.

Objective

Conduct a systematic review and meta-analysis to determine the updated prevalence of diabetes and prediabetes in Peru.

Methodology

An exhaustive analysis of studies published in PubMed, Web of Science, SCOPUS, EMBASE, Scielo, and LILACS databases was conducted. Both national and subnational studies reporting prevalence rates of diabetes and prediabetes using different diagnostic methods and representative sampling techniques were included. Data were synthesized through meta-analysis, evaluating heterogeneity and trends over time and across regions.

Results

Eight studies provided data on the prevalence of DM, while six studies reported on prediabetes. The meta-analysis calculated an overall prevalence of DM at 5.90% (95% CI: 3.98% - 8.17%) and prediabetes at 13.02% (95% CI: 6.31% - 21.68%). Both conditions showed increasing trends over time, with recent studies indicating prevalence rates as high as 10%. However, there was substantial variability in prediabetes rates, ranging from 3.62% to 24.5%.

Conclusions

The findings underscore the need for standardization in diagnostic methods and the implementation of more extensive and representative national studies. To mitigate the impact of these chronic conditions, public health policies should focus on early detection and prevention.
Characterization of highly pathogenic avian influenza virus in retail dairy products in the US
Authors: Spackman Erica , Jones Deana R. , McCoig Amber M. , Colonius Tristan J. , Goraichuk Iryna , Suarez David L.
Published: May 2024

In March 2024 Clade 2.3.4.4b H5N1 highly pathogenic avian influenza virus (HPAIV) was detected in dairy cattle in the US and it was discovered that the virus could be detected in raw milk. Although affected cow’s milk is diverted from human consumption and current pasteurization requirements are expected to reduce or eliminate HPAIV from the milk supply, a study was conducted to characterize whether the virus could be detected by quantitative real-time RT-PCR (qrRT-PCR) in pasteurized retail dairy products and if detected, to determine whether the virus was viable. From April 18 to 22, 2024 a total of 297 samples of Grade A pasteurized retail milk products (23 product types) were collected from 17 US states and represented products from 132 processors in 38 states. Viral RNA was detected in 60 samples (20.2%) with titer equivalents of up to 5.4log1050% egg infectious doses (EID50) per ml, with a mean and median of 3.0log10/ml and 2.9log10/ml respectively. Samples that were positive for type A influenza by qrRT-PCR were confirmed to be clade 2.3.4.4 H5 HPAIV by qrRT-PCR. No infectious virus was detected in any of the qrRT-PCR positive samples in embryonating chicken eggs. Further studies are needed to monitor the milk supply but these results provide evidence that infectious virus did not enter the US pasteurized milk supply before control measures for HPAIV were implemented in dairy cattle.

Importance

Highly pathogenic avian influenza virus (HPAIV) infections in US dairy cattle were first confirmed in March 2024. Because the virus could be detected in raw milk a study was conducted to determine whether it had entered the retail food supply. Pasteurized dairy products were collected from 17 states in April 2024. Viral RNA was detected in 1 in 5 samples but infectious virus was not detected. This provides a snap-shot of HPAIV in milk products early in the event and reinforces that with numerous safety measures, infectious virus in milk is unlikely to enter the food supply.
Peculiar transcriptional reprogramming with functional impairment of dendritic cells upon exposure to transformed HTLV-1-infected cells
Authors: Carcone Auriane , Mortreux Franck , Alais Sandrine , Mathieu Cyrille , Journo Chloé , Dutartre Hélène
Published: May 2024

Manipulation of immune cell functions, independently of direct infection of these cells, emerges as a key process in viral pathophysiology. Chronic infection by Human T-cell Leukemia Virus type 1 (HTLV-1) is associated with immune dysfunctions, including misdirected responses of dendritic cells (DCs). Here, we interrogate the ability of transformed HTLV-1-infected T cells to manipulate human DC functions. We show that exposure to transformed HTLV-1-infected T cells induces a biased and peculiar transcriptional signature in monocyte-derived DCs, associated with an inefficient maturation and a poor responsiveness to subsequent stimulation by a TLR4 agonist. This poor responsiveness is also associated with a unique transcriptional landscape characterized by a set of genes whose expression is either conferred, impaired or abolished by HTLV-1 pre-exposure. Induction of this functional impairment requires several hours of coculture with transformed HTLV-1-infected cells, and associated mechanisms driven by viral capture, cell-cell contacts, and soluble mediators. Altogether, this cross-talk between infected T cells and DCs illustrate how HTLV-1 might co-opt communications between cells to induce a unique local tolerogenic immune microenvironment suitable for its own persistence.

Significance

Chronic viral infection is associated with an escape from immune surveillance. This may rely on the induction of inappropriate DC responses, which can contribute to immunopathology. Immune dysfunctions have been repeatedly reported in people living with Human T-cell Leukemia Virus type 1 (HTLV-1), years before fatal clinical symptom onset, including misdirected responses of dendritic cells (DCs). Here, we report that HTLV-1-infected T cells actively manipulate neighboring, uninfected MDDC functions by rewiring their transcriptional response, leading to a biased, pro-tolerogenic responsiveness in MDDCs, induced by the bidirectional release of soluble mediators, in cooperation with mechanisms dependent on cell-cell contacts. This cross-talk illustrate how HTLV-1 might co-opt communications between cells to induce a local tolerogenic immune microenvironment suitable for its own persistence
Inducible transposon mutagenesis for genome-scale forward genetics
Authors: Basta David W. , Campbell Ian W. , Sullivan Emily J. , Hotinger Julia A. , Hullahalli Karthik , Waldor Matthew K.
Published: May 2024

Transposon insertion sequencing (Tn-seq) is a powerful method for genome-scale functional genetics in bacteria. However, its effectiveness is often limited by a lack of mutant diversity, caused by either inefficient transposon delivery or stochastic loss of mutants due to population bottlenecks. Here, we introduce “InducTn-seq”, which leverages inducible mutagenesis for temporal control of transposition. InducTn-seq generates millions of transposon mutants from a single colony, enabling the sensitive detection of subtle fitness defects and transforming binary classifications of gene essentiality into a quantitative fitness measurement across both essential and non-essential genes. Using a mouse model of infectious colitis, we show that InducTn-seq bypasses a highly restrictive host bottleneck to generate a diverse transposon mutant population from the few cells that initiate infection, revealing the role of oxygen-related metabolic plasticity in pathogenesis. Overall, InducTn-seq overcomes the limitations of traditional Tn-seq, unlocking new possibilities for genome-scale forward genetic screens in bacteria.
BCOR-Rearranged Sarcomas:In SilicoInsights into Altered Domains and Reduced RAWUL-PUFD Binding
Authors: Madarász Kristóf , Mótyán János András , Chien Yi-Che Chang , Bedekovics Judit , Csoma Szilvia Lilla , Méhes Gábor , Mokánszki Attila
Published: May 2024

BCOR(BCL-6 corepressor)-rearranged small round cell sarcoma (BRS) is a rare soft tissue tumor, mostly featuring theBCOR::CCNB3fusion, with other fusions likeBCOR::MAML3,BCOR::CLGN,ZC3H7B::BCOR,KMT2D::BCOR,CIITA::BCOR, andRTL9-BCORalso reported. BCOR, a Polycomb Repressive Complex 1 (PRC1) component, influences histone modifications. It dimerizes with Polycomb group RING finger homolog (PCGF1) via its PCGF ubiquitin-like fold discriminator (PUFD) domain interacting with PCGF1’s RING finger and WD40-associated ubiquitin-like (RAWUL) domain. We used variousin silicotools to explore the impact of fusion events on BCOR’s functionality and RAWUL-PUFD dimer binding affinity. Changes were found in the domain landscapes, physicochemical properties, GO terms and significant increases in the disordered regions within the PUFD domain of the fusion proteins. Structural predictions indicated modified intermolecular contacts (ICs) and a significant reduction in binding affinity in fusion protein RAWUL-PUFD dimers. These findings align with expression data showing PRC1-regulated gene upregulation in BRS, likely due to reduced RAWUL-PUFD binding affinity, impacting dimer formation and PRC1 assembly. Our findings enhance the understanding of BRS oncogenesis and identify potential therapeutic targets.
A Novel Approach for Using Thermal Imaging to Study Behavioural Responses to Environmental Stressors in Passerines
Authors: Roy Joseph , Macleod Ross
Published: May 2024

Infrared thermography is a promising tool for assessing proxy for stress response in animals. With the advancement of longer recording capabilities, this technique allows the monitoring of the dynamic nature of the temperature variation which is highly correlated to the stress faced by the animal. The current method of extraction of data from thermal videos involves manual identification of the beginning and end of the activity (feeding bout in our case) and extracting the temperature data into CSV files. In this paper, we aim to identify the beginning and ending of the feeding bout by the Identification of Temperature Change (ITC) that happens when a bird arrives and leaves the frame. By identifying this we can monitor longer IRT videos and extract the thermal imaging data for stress monitoring in a faster manner. The identification of the beginning and end frames, also allows us to get behavioural data such as feeding bout length and feeding frequency which also act as a proxy for perceived stress. This method was developed to simplify the data analysis process of thermal imaging videos and proved to be an effective method with wider applications in behavioural monitoring based on temperature change.
Temporal Coherence Shapes Cortical Responses to Speech Mixtures in a Ferret Cocktail Party
Authors: Joshi Neha , Ng Yu , Thakkar Karran , Duque Daniel , Yin Pingbo , Fritz Jonathan , Elhilali Mounya , Shamma Shihab
Published: May 2024

Segregation of complex sounds such as speech, music and animal vocalizations as they simultaneously emanate from multiple sources (referred to as the “cocktail party problem”) is a remarkable ability that is common in humans and animals alike. The neural underpinnings of this process have been extensively studied behaviorally and physiologically in non-human animals primarily with simplified sounds (tones and noise sequences). In humans, segregation experiments utilizing more complex speech mixtures are common; but physiological experiments have relied on EEG/MEG/ECoG recordings that sample activity from thousands of neurons, often obscuring the detailed processes that give rise to the observed segregation. The present study combines the insights from animal single-unit physiology with segregation of speech-like mixtures. Ferrets were trained to attend to a female voice and detect a target word, both in presence or absence of a concurrent, equally salient male voice. Single neuron recordings were obtained from primary and secondary ferret auditory cortical fields, as well as frontal cortex. During task performance, representation of the female words became more enhanced relative to those of the (distractor) male in all cortical regions, especially in the higher auditory cortical field. Analysis of the temporal and spectral response characteristics during task performance reveals how speech segregation gradually emerges in the auditory cortex. A computational model evaluated on the same voice mixtures replicates and extends these results to different attentional targets (attention to female or male voices). These findings are consistent with the temporal coherence theory whereby attention to a target voice anchors neural activity in cortical networks hence binding together channels that are coherently temporally-modulated with the target, and ultimately forming a common auditory stream.
How cortico-basal ganglia-thalamic subnetworks can shift decision policies to maximize reward rate
Authors: Bahuguna Jyotika , Verstynen Timothy , Rubin Jonathan E.
Published: May 2024

All mammals exhibit flexible decision policies that depend, at least in part, on the cortico-basal ganglia-thalamic (CBGT) pathways. Yet understanding how the complex connectivity, dynamics, and plasticity of CBGT circuits translate into experience-dependent shifts of decision policies represents a longstanding challenge in neuroscience. Here we present the results of a computational approach to address this problem. Specifically, we simulated decisions driven by CBGT circuits under baseline, unrewarded conditions using a spiking neural network, and fit an evidence accumulation model to the resulting behavior. Using canonical correlation analysis, we then replicated the identification of three control ensembles (responsiveness,pliancyandchoice) within CBGT circuits, with each of these subnetworks mapping to a specific configuration of the evidence accumulation process. We subsequently simulated learning in a simple two-choice task with one optimal (i.e., rewarded) target and found that feedback-driven dopaminergic plasticity on cortico-striatal synapses effectively manages the speed-accuracy tradeoff so as to increase reward rate over time. The learning-related changes in the decision policy can be decomposed in terms of the contributions of each control ensemble, whose influence is driven by sequential reward prediction errors on individual trials. Our results provide a clear and simple mechanism for how dopaminergic plasticity shifts subnetworks within CBGT circuits so as to maximize reward rate by strategically modulating how evidence is used to drive decisions.

Author summary

The task of selecting an action among multiple options can be framed as a process of accumulating streams of evidence, both internal and external, up to a decision threshold. A decision policy can be defined by the unique configuration of factors, such as accumulation rate and threshold height, that determine the dynamics of the evidence accumulation process. In mammals, this process is thought to be regulated by low dimensional subnetworks, called control ensembles, within the cortico-basal ganglia-thalamic (CBGT) pathways. These control ensembles effectively act by tuning specific aspects of evidence accumulation during decision making. Here we use simulations and computational analysis to show that synaptic plasticity at the cortico-striatal synapses, mediated by choice-related reward signals, adjusts CBGT control ensemble activity in a way that improves accuracy and reduces decision time to maximize the increase of reward rate during learning.