bluuebunny/crossref_metadata_2025 huggingface dataset:
Challenges in using data on fathers/partners to study prenatal exposures and offspring health
Authors: Easey Kayleigh E , Gkatzionis Apostolos , Millard Louise AC , Tilling Kate , Lawlor Deborah A , Sharp Gemma C
Published: August 2023

Introduction

Paternal exposures (and other non-maternal factors) around pregnancy could have important effects on offspring health. One challenge in research of paternal effects is that study samples with data on partners are usually a subgroup of those with data on mothers, which could introduce selection bias and limit generalisability of the findings. Here, we use maternal and father/partner data on prenatal behaviours to explore the extent to which selection in partner analyses might bias findings.

Methods

We characterise the availability of data on father/partner and mother health behaviours (smoking, alcohol consumption, caffeine consumption and physical activity) in the prenatal period from three UK cohort studies: the Avon Longitudinal Study of Parents and Children (ALSPAC), Born in Bradford (BiB) and the Millennium Cohort Study (MCS). We assess the extent of sample selection in these cohorts by comparing the characteristics of families where the father/partner does and does not participate. Using the association of parental smoking during pregnancy and child birthweight as an exemplar, we used simulations to explore the extent to which missing father/partner data may bias estimates.

Results

In all three cohorts, data on prenatal health behaviours of fathers/partners were less detailed and collected at fewer timepoints than data on prenatal health behaviours of mothers. Partners of mothers who had a lower socioeconomic position were less likely to participate. Estimates of the association between maternal smoking and offspring birthweight were similar in samples with and without participating partners in all three cohorts. In simulations based on ALSPAC data, there was little evidence of selection bias in associations of maternal smoking with birthweight, and although bias was observed for father/partner smoking, its magnitude was relatively small.

Discussion

Using real and simulated data, we show that bias due to selected recruitment of partners into ALSPAC, BiB and MCS had a relatively small impact on estimates of the effects of maternal and partner smoking on offspring birthweight. In other applications, the impact of selection bias will depend on both the analysis model and the selection mechanism. We have shown how to use a simulation study to assess that and recommend that applied researchers working with partner data use simulations and other sensitivity analyses to assess the robustness of their results.
What are the impacts of oral complications from cancer therapy on the quality of life of children? A protocol to update a scoping review
Authors: Attaran Nona , Sharma Apoorva , Morris Martin , Dudubo Olawale , Macdonald Mary Ellen
Published: August 2023

Introduction

Cancer treatments can damage healthy tissues and organs, and leave harmful impacts on cancer survivors, especially on children and adolescents. The oral effects of cancer treatment can occur during or soon after treatment, or months – even years – later. Cancer treatments can also affect the child, psychologically and socially by hindering their speech, eating, sleeping, and social interactions. These effects can have profound impacts on children’s quality of life. Building on a previous review published in 2012, this scoping review aims to identify and map the current evidence base underpinning the oral health-related impacts of cancer treatment on the quality of life of children with cancer.

Methodology and methods

Our methodology is guided by Arksey and O’Malley’s methodological framework for scoping reviews, Levac’s additions to the framework, and follows the Joanna Briggs Institute Reviewer’s Manual. Five electronic databases and grey literature will be systematically searched using a predefined search strategy. Two reviewers will independently screen the retrieved articles using Rayyan software and chart data from included articles. One of the team’s senior research members will act as a third reviewer and make the final decision on disputed documents. We will include literature with a focus on oral health-related quality of life of children undergoing cancer treatments. Following the selection of studies, data will be extracted, synthesized, and reported thematically and the relevant stakeholder’s insight will be added to our results.

Ethics and dissemination

No ethical approval is required as exclusively secondary data will be used. Results will be disseminated in cancer and oral health conferences, symposia, and a peer-reviewed journal. The information extracted from this review will also be the base for a qualitative study on the quality-of-life impacts of oral health effects of childhood cancer including children’s perspectives.
Prevalence and factors associated with abdominal and total obesity among low-income urban population of Kiambu County, Kenya
Authors: Mbuthia Grace Wambura , Ndithia James Mwangi , Oguta James Odhiambo , Akoth Catherine , Magutah Karani , Kawira Rosemary , Nyariki Caroline , Kimutai Nickson , Kinyua Agnes , McGarvey Stephen T.
Published: August 2023

Obesity is a major risk factor for most non-communicable diseases whose burden has been rising rapidly in low and middle-income countries. To develop public health interventions to address the increasing burden of overweight and obesity, estimates of the prevalence and associated factors are needed in specific populations. The study sought to determine the prevalence and factors associated with total obesity and abdominal obesity among low-income adults in Kiambu County, Kenya. This community-based cross-sectional survey involved 1656 adults residing in Kiambu County. Multistage sampling was used in the selection of participants. Data were collected by trained community health volunteers (CHVs) in their respective sub-counties using an interviewer-administered questionnaire. The CHVs also took anthropometric measurements using relevant tools and standard procedures. Descriptive statistics were used to describe the participants’ characteristics and proportions of adults with obesity. Multivariable logistic regression analyses were performed to assess the factors associated with obesity. The mean age of participants was 40.8 (±14.3) years The overall prevalence of total obesity (body mass index [BMI]>30 kg/m2) was 28.8% (95% CI, 26.6%-30.9%), with a higher prevalence observed among females [33.6% (95% CI, 31.1%-36.2%)] than males [12.5% (95% CI, 9.6%-16.3%)]. A third (33.3%) of the participants were overweight (25<BMI < 30 kg/m2). The prevalence of abdominal obesity as measured by waist-height-ratio (WHtR) was 79.8%, by waist circumference (WC) was 74.0%. Obesity/overweight by BMI was associated with female gender, increasing age, monthly income, while abdominal obesity by WHtR/WC was associated with female gender, increasing age and cigarrete smoking. In conclusion, the prevalence of total obesity and abdominal obesity was high in the population. Public health strategies focusing on weight reduction and maintenance strategies are urgently needed among low-income adults.
Epidemiology and Survival outcomes of HIV-associated cervical cancer in Nigeria
Authors: Musa Jonah , Kocherginsky Masha , Magaji Francis A. , Maryam Ali J. , Asufi Joyce , Nenrot Danjuma , Burdett Kristen , Katam Neelima , Christian Elizabeth N. , Palanisamy Nisha , Odukoya Olukemi , Silas Olugbenga A. , Abdulkareem Fatimah , Akpa Philip , Badmos Kabir , Imade Godwin E. , Akanmu Alani S. , Gursel Demirkan B. , Zheng Yinan , Joyce Brian T. , Achenbach Chad J. , Sagay Atiene S. , Anorlu Rose , Wei Jian-Jun , Ogunsola Folasade , Murphy Robert L. , Hou Lifang , Simon Melissa A.
Published: August 2023

Introduction

Invasive cervical cancer (ICC) is an HIV-associated cancer that is preventable and precancerous stages including early ICC stages could be detected through screening offering opportunities for treatment and cure. The high incidence in women living with HIV and late presentation often at advanced stages of ICC with limited treatment facilities often result in early mortality. We sought to compare the epidemiologic characteristics and survival differences in HIV status of ICC patients in Nigeria.

Methods

We conducted a cohort study at two federal academic hospital-based research sites in Jos University Teaching Hospital, and Lagos University Teaching Hospital Nigeria, between March 2018 and September 2022. We enrolled women with histologically confirmed ICC with known HIV status, and FIGO staging as part of the United States of America’s National Institutes of Health/National Cancer Institute funded project titled ‘Epigenomic Biomarkers of HIV-Associated Cancers in Nigeria’. The primary outcome was all-cause mortality with assessment of overall survival (OS) and time to death after ICC diagnosis. OS distribution was estimated using the method of Kaplan-Meier and compared between groups using the log-rank test.

Results

A total of 239 women with confirmed ICC were enrolled and included in this analysis, of whom 192 (80.3%) were HIV-negative (HIV-/ICC+), and 47 (19.7%) were HIV-positive (HIV+/ICC+). The HIV+/ICC) patients were younger with median age 46 (IQR: 40-51) years compared to 57 (IQR: 45-66) among HIV-/ICC+) (P<0.001. Squamous cell carcinoma was the commonest histopathologic variant in 80.4% of ICC diagnosis, moderately differentiated tumor grade in 68.1% in both groups. HIV+/ICC+ diagnosis was at FIGO advanced stages in 64.9% compared to 47.9% in HIV-/ICC+. The HIV-/ICC+ women had better OS compared to HIV+/ICC+ participants (p=0.018), with 12-month OS 84.1% (95%CI: 75% - 90%) and 67.6% (95%CI: 42%-84%) respectively.

Conclusion

ICC is diagnosed at a relatively young age in women living with HIV, with a significantly lower overall survival probability compared to women without HIV. The trend of presentation and diagnosis at advanced stages in women living with HIV could partly explain the differences in overall survival.
Physicians’ attitudes and perceived barriers toward ward-based clinical pharmacist in hospital settings: Responses from a national survey
Authors: Hatem Najmaddin A. H. , Kubas Mohammed A. , Yousuf Seena A. , Rasam Abdunaser , Ibrahim Mohamed Izham Mohamed
Published: August 2023

Clinical pharmacy services CPSs are still in their infancy in Yemen. Furthermore, pharmacists are not members of a multidisciplinary healthcare team, and their responsibilities are limited to drug dispensing and marketing. Thus, this study investigates physicians’ attitudes and perceived obstacles toward clinical pharmacists working in hospitals’ medical wards. A descriptive observational study was carried out using a validated self-administrated bilingual questionnaire. The study’s questionnaire was conducted among physicians in three teaching hospitals. Those hospitals were at the front to establish clinical pharmacy units and embrace clinical pharmacy services. Sixty-five responses were included. our data results indicated that physicians believed the most contributions for clinical pharmacists to improve patient care was “Attend medical rounds” 70.8%, followed by “Order review”. About 75% of physicians showed positive attitudes toward the clinical pharmacist role. However, more than 70% of physicians thought that clinical pharmacists should leave patient care to other healthcare members and care about drug products. There were Nine potential barriers out of 18 barriers were identified. Not enough clinical pharmacist staff working in the health center was considered as the top perceived barrier 83.1%; followed by clinical pharmacist responsibilities were not clearly defined”, and “clinical pharmacist recommendations are not properly documented”. In terms of enhancing physicians’ general attitudes and overcoming reported barriers. Strategies to expand clinical pharmacy services in Yemen should be emphasized on both, protocols should be established to outline how clinical pharmacists and physicians should collaborate besides, inter-professional collaboration relations are needed to be developed to overcome resistance and raise knowledge and awareness of CPS adoption among the healthcare team members.
Sensitive periods for exposure to indoor air pollutants and psychosocial factors in association with symptoms of psychopathology at school-age in a South African birth cohort
Authors: Christensen Grace M. , Marcus Michele , Vanker Aneesa , Eick Stephanie M. , Malcolm-Smith Susan , Smith Andrew D.A.C. , Dunn Erin C. , Suglia Shakira F. , Chang Howard H. , Zar Heather J. , Stein Dan J. , Hüls Anke
Published: August 2023

Background

Gestation and the first few months of life are important periods for brain development. During these periods, exposure to environmental toxicants and psychosocial stressors are particularly harmful and may impact brain development. Specifically, exposure to indoor air pollutants (IAP) and psychosocial factors (PF) during these sensitive periods has been shown to predict childhood psychopathology.

Objectives

This study aims to investigate sensitive periods for the individual and joint effects of IAP and PF on childhood psychopathology at 6.5 years.

Methods

We analyzed data from the Drakenstein Child Health Study (N=599), a South African birth cohort. Exposure to IAP and PF was measured during the second trimester of pregnancy and 4 months postpartum. The outcome of childhood psychopathology was assessed at 6.5 years old using the Childhood Behavior Checklist (CBCL). We investigated individual effects of either pre-or postnatal exposure to IAP and PF on CBCL scores using adjusted linear regression models, and joint effects of these exposures using quantile g-computation and self-organizing maps (SOM). To identify possible sensitive periods, we used a structured life course modeling approach (SLCMA) as well as exposure mixture methods (quantile g-computation and SOM).

Results

Prenatal exposure to IAP or PFs, as well as the total prenatal mixture assessed using quantile g-computation, were associated with increased psychopathology. SLCMA and SOM models also indicated that the prenatal period is a sensitive period for IAP exposure on childhood psychopathology. Depression and alcohol were associated in both the pre-and postnatal period, while CO was associated with the postnatal period.

Discussion

Pregnancy may be a sensitive period for the effect of indoor air pollution on childhood psychopathology. Exposure to maternal depression and alcohol in both periods was also associated with psychopathology. Determining sensitive periods of exposure is vital to ensure effective interventions to reduce childhood psychopathology.
Unique Capabilities of Genome Sequencing for Rare Disease Diagnosis
Authors: Wojcik Monica H , Lemire Gabrielle , Zaki Maha S , Wissman Mariel , Win Wathone , White Sue , Weisburd Ben , Waddell Leigh B , Verboon Jeffrey M , VanNoy Grace E. , Töpf Ana , Tan Tiong Yang , Straub Volker , Stenton Sarah L , Snow Hana , Singer-Berk Moriel , Silver Josh , Shril Shirlee , Seaby Eleanor G , Schneider Ronen , Sankaran Vijay G , Sanchis-Juan Alba , Russell Kathryn A , Reinson Karit , Ravenscroft Gianina , Pierce Eric A , Place Emily M , Pajusalu Sander , Pais Lynn , Õunap Katrin , Osei-Owusu Ikeoluwa , Okur Volkan , Oja Kaisa Teele , O’Leary Melanie , O’Heir Emily , Morel Chantal , Marchant Rhett G , Mangilog Brian E , Madden Jill A , MacArthur Daniel , Lovgren Alysia , Lerner-Ellis Jordan P , Lin Jasmine , Laing Nigel , Hildebrandt Friedhelm , Groopman Emily , Goodrich Julia , Gleeson Joseph G , Ghaoui Roula , Genetti Casie A , Gazda Hanna T , Ganesh Vijay S. , Ganapathy Mythily , Gallacher Lyndon , Fu Jack , Evangelista Emily , England Eleina , Donkervoort Sandra , DiTroia Stephanie , Cooper Sandra T , Chung Wendy K , Christodoulou John , Chao Katherine R , Cato Liam D , Bujakowska Kinga M , Bryen Samantha J , Brand Harrison , Bonnemann Carsten , Beggs Alan H , Baxter Samantha M , Agrawal Pankaj B , Talkowski Michael , Austin-Tse Chrissy , Rehm Heidi L , O’Donnell-Luria Anne
Published: August 2023

Background

Causal variants underlying rare disorders may remain elusive even after expansive gene panels or exome sequencing (ES). Clinicians and researchers may then turn to genome sequencing (GS), though the added value of this technique and its optimal use remain poorly defined. We therefore investigated the advantages of GS within a phenotypically diverse cohort.

Methods

GS was performed for 744 individuals with rare disease who were genetically undiagnosed. Analysis included review of single nucleotide, indel, structural, and mitochondrial variants.

Results

We successfully solved 218/744 (29.3%) cases using GS, with most solves involving established disease genes (157/218, 72.0%). Of all solved cases, 148 (67.9%) had previously had non-diagnostic ES. We systematically evaluated the 218 causal variants for features requiring GS to identify and 61/218 (28.0%) met these criteria, representing 8.2% of the entire cohort. These included small structural variants (13), copy neutral inversions and complex rearrangements (8), tandem repeat expansions (6), deep intronic variants (15), and coding variants that may be more easily found using GS related to uniformity of coverage (19).

Conclusion

We describe the diagnostic yield of GS in a large and diverse cohort, illustrating several types of pathogenic variation eluding ES or other techniques. Our results reveal a higher diagnostic yield of GS, supporting the utility of a genome-first approach, with consideration of GS as a secondary or tertiary test when higher-resolution structural variant analysis is needed or there is a strong clinical suspicion for a condition and prior targeted genetic testing has been negative.
Factors associated with exclusive breastfeeding among mothers of children under two years of age in Dalit community, Rajbiraj Municipality, Saptari, Nepal
Authors: Das Neha Kumari , Duwadi Nirmal , Sinha Ramchandra , Dahal Alisha
Published: August 2023

The prevalence of exclusive breastfeeding (EBF) is suboptimal in Nepal and very low in Madhesh province. Dalits are commonly recognized for experiencing economic exploitation, a lack of political representation, social marginalization, educational disadvantage, being classified as untouchables, and enduring the denial of basic human dignity and social justice.

Objective of this study is to assess the proportion of mothers of children under 2 years of age, practicing exclusive breastfeeding and associated factors in the Dalit community of Rajbiraj Municipality, Saptari, Nepal.

The study utilized an analytical, cross-sectional design by using a semi-structured questionnaire to 156 Dalit mothers of children under 2 years of age in Rajbiraj Municipality, Saptari, Nepal. In the bivariate analysis, which focuses on exploring the connection between independent variables and dependent variables, chi-squire statistics were utilized. Subsequently, the independent variables that displayed significance in the bivariate analysis were included in the multivariate logistic regression.

The estimated prevalence of exclusive breastfeeding in the population was 43.6%. Mother’s occupation (adjusted odds ratio (AOR = 4.459; CI = 1.444 -13.767), smoking habit (AOR = 2.755; CI = 1.120 – 6.774), colostrum milk feeding (AOR = 12.472; CI = 3.253 – 47.823), number of times visit the health center for ANC (AOR = 2.333; CI = 1.040 – 5.233) were positively associated with exclusive breastfeeding, whereas, sex of the child, type of family, knowledge about breastfeeding, counselling on EBF in ANC and/or PNC visit were also associated with exclusive breastfeeding. Among the respondents who did not practice exclusive breastfeeding, the common reasons cited were trouble initiating milk flow (23.7%), insufficient breast milk production (21.7%), breast milk not satisfying the baby (20.9%), domestic work burden (12%), difficulties with infant sucking or latching (6.4%), and the baby being unable to be breastfed owing to sickness (4.8%).

Maternal education, occupation, colostrum milk feeding, and antenatal care visits were identified as important influencers of exclusive breastfeeding. Healthcare professionals, policymakers, and community leaders can utilize these insights to formulate effective strategies and design intervention that encourage and support exclusive breastfeeding among Dalit mothers, ultimately improving the health and well-being of the infants of the marginalized community.
Effect of regional deprivation on mental and physical health: a longitudinal natural experiment among refugees in Germany
Authors: Biddle Louise , Bozorgmehr Kayvan
Published: August 2023

Background

Existing studies on contextual health effects struggle to account for selection bias, limiting causal interpretation. We use refugee dispersal in Germany as natural experiment to study the effect of small-area deprivation on mental and physical health, while considering the potential mediating role of housing and social context.

Methods

Refugees subject to dispersal (n=1400) are selected from a nation-wide longitudinal refugee study (IAB-SOEP-BAMF Panel; 2016-2018). Multi-level linear regression models, adjusted for age, sex, education, region of origin, federal state, asylum status and length of residence in Germany, are fitted to the change in mental and physical health subscales of the SF-12 depending on quintiles (Q1 – Q5) of district-level socioeconomic deprivation (German Index of Socio-Economic Deprivation, GISD). This is followed by mediation analyses (for housing and social context) and sensitivity analyses.

Findings

Residency in districts with moderate-high deprivation (Q4) has a negative impact on physical health (coef·: -2·2, 95%CI: -4·1;-0·2) compared to lowest deprivation (Q1). Moderate-high deprivation (Q4) also has a positive impact on mental health, but the effect is statistically insignificant following covariate adjustment (coef·: 2·5, 95%CI: -0·7;5·6). Comparisons with other deprivation quintiles are statistically insignificant.

Interpretation

The results point to gaps in health and social service provision for refugees living in the most deprived regions. Further efforts should be made to support integration of refugees into health and social systems in resource-poor regions, including improved interpreting services, specifically trained social workers and diversity-sensitive information offerings. Further research using longer timeframes and larger sample sizes are required to confirm results.

Funding

German Science Foundation (FOR: 2928/ GZ: BO5233/1-1).
Whole-genome mapping of APOBEC mutagenesis in metastatic urothelial carcinoma identifies driver hotspot mutations and a novel mutational signature
Authors: Nakauma-González J. Alberto , Rijnders Maud , Noordsij Minouk T. W. , Martens John W. M. , van der Veldt Astrid , Lolkema Martijn P. , Boormans Joost L. , van de Werken Harmen J.G.
Published: August 2023

APOBEC enzymes mutate specific DNA sequences and hairpin-loop structures, challenging the distinction between passenger and driver hotspot mutations. Here, we characterized 115 whole-genomes of metastatic urothelial carcinoma (mUC) to identify APOBEC mutagenic hotspot drivers. APOBEC-associated mutations were detected in 92% of mUC and were equally distributed across the genome, while APOBEC hotpot mutations (ApoHM) were enriched in open chromatin. Hairpin-loops were frequent targets of didymi (twins in Greek), two hotpot mutations characterized by the APOBEC mutational signature SBS2, in conjunction with an uncharacterized mutational context (Ap[C>T]), which was associated with DNA mismatch. Next, we developed a statistical framework that identified 0.40% of ApoHM as drivers of mUC, which affected known driver genes and non-coding regions near exons of potential novel driver genes. Our results and statistical framework were validated in independent cohorts of 23 non-metastatic UC and 3744 samples of 17 metastatic cancers, identifying cancer-type-specific drivers. Our study highlights the role of APOBEC in cancer development and may contribute to developing novel targeted therapy options for APOBEC-driven mUC.
An epidemiological study of season of birth, mental health, and neuroimaging in the UK Biobank
Authors: Viejo-Romero Maria , Whalley Heather C. , Shen Xueyi , Stolicyn Aleks , de Nooij Laura , Smith Daniel J. , Howard David M.
Published: August 2023

Environmental exposures during the perinatal period are known to have a long-term effect on adult physical and mental health. One such influential environmental exposure is the time of year of birth which affects the amount of daylight, nutrients, and viral load that an individual is exposed to in the key developmental period. Here we investigate associations between season of birth (seasonality), four mental health traits (n=135,541) and multi-modal neuroimaging measures (n=33,815) within the UK Biobank. Summer births were associated with probable recurrent Major Depressive Disorder (β=0.024,pcorr=0.048), greater mean cortical thickness in temporal and occipital lobes and in the middle temporal, fusiform, superior temporal, and lingual gyri regions (β range=0.013 - 0.020,pcorr<0.05). Winter births were associated with greater white matter integrity globally, in the association fibers, thalamic radiations, and six individual tracts (β range=-0.010 to -0.021,pcorr<0.05). Results of sensitivity analyses that adjusted for birth weight were similar, with additional associations found between winter birth and frontal, occipital and cingulate lobe surface areas, as well as fractional anisotropy in the forceps minor. Sensitivity analyses also revealed an additional association between summer birth and greater cingulate thickness. Overall, results suggest that seasonality affects brain structure in later life and may have a role in lifetime recurrent Major Depressive Disorder. The small effect sizes observed here warrant further research to validate the results in the context of different latitudes and co-examine genetic and epigenetic measures to potentially reveal informative biological pathways.
The effect of sepsis recognition on telemedicine use and bundle completion in rural emergency department sepsis treatment
Authors: Kaldjian Anna M. , Vakkalanka J. Priyanka , Okoro Uche , Wymore Cole , Harland Karisa K. , Campbell Kalyn , Swanson Morgan B. , Fuller Brian M. , Faine Brett , Zepeski Anne , Parker Edith A. , Mack Luke , Bell Amanda , DeJong Katie , Wallace Kelli , Mueller Keith , Chrischilles Elizabeth , Carpenter Christopher R. , Jones Michael P. , Ward Marcia M. , Mohr Nicholas M.
Published: August 2023

Purpose

Provider-to-provider emergency department telehealth (tele-ED) has been proposed to improve rural sepsis care. The objective of this study was to measure the association between sepsis documentation and tele-ED use, treatment guideline adherence, and mortality.

Materials and Methods

This analysis was a multicenter (n=23) cohort study of sepsis patients treated in rural emergency departments (EDs) that participated in a tele-ED network between August 2016 and June 2019. The primary exposure was whether sepsis was recognized in the local ED, and the primary outcome was rural tele-ED use, with secondary outcomes of time to tele-ED use, 3-hour guideline adherence, and in-hospital mortality.

Results

Data from 1,146 rural sepsis patients were included, 315 (27%) had tele-ED used, and 415 (36%) had sepsis recognized in the rural ED. Sepsis recognition was not independently associated with higher rates of tele-ED use (adjusted odds ratio [aOR] 1.23, 95% CI 0.90–1.67). Sepsis recognition was associated with earlier tele-ED activation (adjusted hazard ratio [aHR] 1.69, 95% CI 1.34-2.13), lower 3-hour guideline adherence (aOR 0.73, 95% CI: 0.55-0.97), and lower in-hospital mortality (aOR 0.72, 95% CI: 0.54-0.97).

Conclusions

Sepsis recognition in rural EDs participating in a tele-ED network was not associated with tele-ED use.
Integrating genome and epigenome data to identify tissue-specific DNA methylation biomarkers for cancer risk
Authors: Yang Yaohua , Chen Yaxin , Xu Shuai , Guo Xingyi , Jia Guochong , Ping Jie , Shu Xiang , Zhao Tianying , Yuan Fangcheng , Wang Gang , Xie Yufang , Ci Hang , Liu Dan , Ye Fei , Shu Xiao-Ou , Zheng Wei , Li Li , Cai Qiuyin , Long Jirong
Published: August 2023

The relationship between tissue-specific DNA methylation and cancer risk remains inadequately elucidated. Leveraging the Genotype-Tissue Expression (GTEx) consortium, we developed genetic models to predict DNA methylation at CpG sites (CpGs) across the genome for seven tissues and applied these models to genome-wide association study (GWAS) data of corresponding cancers, namely breast, colorectal, renal cell, lung, ovarian, prostate, and testicular germ cell cancers. At Bonferroni-correctedP<0.05, we identified 2,776 CpGs significantly associated with cancer risk, of which 92.7% (2,572) were specific to a particular cancer type. Notably, 57 CpGs within 35 putative novel loci retained significant associations with cancer risk after conditioning on proximal GWAS-identified signals. Further integrative multi-omics analyses revealed 791 CpG-gene-cancer trios, suggesting that DNA methylation at 248 distinct CpGs might influence cancer risk through regulating expression of 145 uniquecis-genes. These findings substantially advance our understanding of the interplay between genetics, epigenetics, and gene expression in cancer etiology.
Candidate genes for IgA nephropathy in pediatric patients: exome-wide association study
Authors: Buianova Anastasiia A. , Proskura Mariia V. , Cheranev Valery V. , Belova Vera A. , Shmitko Anna O. , Pavlova Anna S. , Vasiliadis Iuliia A. , Suchalko Oleg N. , Rebrikov Denis V. , Petrosyan Edita K. , Korostin Dmitriy O.
Published: August 2023

IgA nephropathy (IgAN) is an autoimmune disorder that commonly manifests during adolescence. This disease is believed to be a non-monogenic disorder related to variations in multiple genes involved in various biological pathways.

We performed the exome-wide association study of 70 children with IgAN confirmed by renal biopsy and 637 healthy donors to identify gene associations responsible for the disease. The HLA allele frequencies between the patients and healthy donors from the bone marrow registry of the Pirogov University were compared. We tested 78,020 gene markers for association, performed the functional enrichment analysis and the transcription factor binding preference detection.

We detected 333 genetic variants, employing three inheritance models. The most significant association with the disorder was observed for rs143409664 (PRAG1) in case of the additive and dominant models (PBONF= 1.808 × 10−15and PBONF= 1.654 × 10−15, respectively) and for rs13028230 (UBR3) in case of the recessive model (PBONF= 1.545 × 10−9). Enrichment analysis indicated the strongly overrepresented “immune system” and “kidney development” terms. The HLA-DQA1*01:01:01G allele (P = 0.0076; OR, 2.021 [95% CI, 1.322-3.048]) was significantly the most frequent among IgAN patients.

Here we characterized, for the first time, the genetic background of the Russian IgAN patients identifying the risk alleles typical of the population. The most prominent signals were detected in previously undescribed loci.
From microbial communities to regional biogeography: Unraveling patterns, determinants and the influence of bottom trawling in benthic microbiota
Authors: Bonthond Guido , Beermann Jan , Gutow Lars , Neumann Andreas , Barboza Francisco Rafael , Desiderato Andrea , Fofonova Vera , Helber Stephanie , Khodami Sahar , Kraan Casper , Neumann Hermann , Rohde Sven , Schupp Peter J.
Published: August 2023

Microbial composition and diversity in marine sediments are shaped by environmental, biological, and anthropogenic processes that operate on different scales. However, our understanding of benthic microbial biogeography remains limited. Here, we study how benthic microbiota vary at a regional scale in the North Sea with sediment characteristics, temperature, organic matter content, shear bed stress and bottom trawling intensity, a prevalent industrial fishing practice which heavily impacts benthic ecosystems. Using 16S rDNA amplicon sequencing, we characterized benthic microbiota from the top centimeter of 349 sediment samples and used uni-and multivariate statistical models, accounting for spatial autocorrelation, to disentangle the effects of the different predictors. Fitted models demonstrate how the geographic interplay of different environmental anthropogenic drivers shapes the structure and functioning of benthic microbial communities. Sediment properties were the primary determinants, with diversity increasing with sediment permeability but at the same time increasing with mud content, highlighting different underlying processes. Alpha diversity also increased nonlinearly with total organic matter content and temperature and showed a more complex relationship with bottom shear stress but decreased with bottom trawling intensity. These trawling associated diversity changes were accompanied by shifts in functional groups related to energy metabolism. Specifically, with increasing trawling intensity, we observed a transition toward more aerobic heterotrophic and less denitrifying metabolism. Our findings provide first insights of benthic microbial biogeographic patterns on a large spatial scale and illustrate how anthropogenic activity such as bottom trawling may influence the distribution and abundances of microbes and overall benthic metabolism at macroecological scales.
Diverse Epithelial Lymphocytes in Zebrafish Revealed Using a Novel Scale Biopsy Method
Authors: Park Gilseung , Foster Clay A. , Malone-Perez Megan , Hasan Ameera , Macias Jose Juan , Frazer J. Kimble
Published: August 2023

Zebrafish are a compelling model to study lymphocytes because zebrafish and humans have similar adaptive immune systems. Human and zebrafish lymphocyte types are conserved, but many aspects of zebrafish lymphocyte biology remain uninvestigated, including lymphocytes in peripheral tissues, like epidermis. Here, we report the first study focused on zebrafish scale epidermal lymphocytes. Zebrafish scales represent a source to longitudinally sample live fish. We developed a novel biopsy technique, collecting scales to analyze epithelial lymphocytes from several fluorescently-labeled lines. We imaged scales via confocal microscopy and demonstrated multiple lymphocyte types in scales/epidermis, quantifying them flow cytometrically. We profiled gene expression of scale, thymic, and marrow lymphocytes from the same animals, revealing B- and T-lineage signatures. Single-cell qRT-PCR and RNA sequencing (scRNAseq) show not only canonical B and T cells, but also novel lymphocyte populations not described previously. To validate longitudinal scale biopsies, we serially sampled scales from fish treated with dexamethasone (DXM), demonstrating epidermal lymphocyte responses. To analyze cells functionally, we employed a bead-ingestion assay, showing thymic, marrow, and epidermal lymphocytes have phagocytic activity. In summary, we establish a non-lethal technique to obtain zebrafish lymphocytes, providing the first quantification, expression profiling, and functional data from epidermal lymphocytes in the zebrafish model.

This study describes a new biopsy method to acquire zebrafish lymphocytes forex vivostudies, without euthanasia. Expression profiles of individual lymphocytes from multiple zebrafish transgenic lines reveal diverse lymphocyte populations, including novel cells expressing genes of both the B- and T-lineages.
TMS provokes target-dependent intracranial rhythms across human cortical and subcortical sites
Authors: Solomon Ethan A. , Wang Jeffrey B. , Oya Hiroyuki , Howard Matthew A. , Trapp Nicholas T. , Uitermarkt Brandt D. , Boes Aaron D. , Keller Corey J.
Published: August 2023

Transcranial magnetic stimulation (TMS) is increasingly deployed in the treatment of neuropsychiatric illness, under the presumption that stimulation of specific cortical targets can alter ongoing neural activity and cause circuit-level changes in brain function. While the electrophysiological effects of TMS have been extensively studied with scalp electroencephalography (EEG), this approach is most useful for evaluating low-frequency neural activity at the cortical surface. As such, little is known about how TMS perturbs rhythmic activity among deeper structures – such as the hippocampus and amygdala – and whether stimulation can alter higher-frequency oscillations. Recent work has established that TMS can be safely used in patients with intracranial electrodes (iEEG), allowing for direct neural recordings at sufficient spatiotemporal resolution to examine localized oscillatory responses across the frequency spectrum. To that end, we recruited 17 neurosurgical patients with indwelling electrodes and recorded neural activity while patients underwent repeated trials of single-pulse TMS at several cortical sites. Stimulation to the dorsolateral prefrontal cortex (DLPFC) drove widespread low-frequency increases (3-8Hz) in frontolimbic cortices, as well as high-frequency decreases (30-110Hz) in frontotemporal areas, including the hippocampus. Stimulation to parietal cortex specifically provoked low-frequency responses in the medial temporal lobe. While most low-frequency activity was consistent with brief evoked responses, anterior frontal regions exhibited induced theta oscillations following DLPFC stimulation. Taken together, we established that non-invasive stimulation can (1) provoke a mixture of low-frequency evoked power and induced theta oscillations and (2) suppress high-frequency activity in deeper brain structures not directly accessed by stimulation itself.
Developmental stability and segregation of Theory of Mind and Pain networks carry distinct temporal signatures during naturalistic viewing
Authors: Bhavna Km , Ghosh Niniva , Banerjee Romi , Roy Dipanjan
Published: August 2023

Temporally stable large-scale functional brain connectivity among distributed brain regions is crucial during brain development. Recently, many studies highlighted an association between temporal dynamics during development and their alterations across various time scales. However, systematic characterization of temporal stability patterns of brain networks that represent the bodies and minds of others in children remains unexplored. To address this, we apply an unsupervised approach to reduce high-dimensional dynamic functional connectivity (dFC) features via low-dimensional patterns and characterize temporal stability using quantitative metrics across neurodevelopment. This study characterizes the development of temporal stability of the Theory of Mind (ToM) and Pain networks to address the functional maturation of these networks. The dataset used for this investigation comprised 155 subjects (children (n=122, 3–12 years) and adults (n=33)) watching engaging movie clips while undergoing fMRI data acquisition. The movie clips highlighted cartoon characters and their bodily sensations (often pain) and mental states (beliefs, desires, emotions) of others, activating ToM and Pain network regions of young children. Our findings demonstrate that ToM and pain networks display distinct temporal stability patterns by age 3 years. Finally, the temporal stability and specialization of the two functional networks increase with age and predict ToM behavior.
Single-cell transcriptional profiling of clear cell renal cell carcinoma reveals an invasive tumor vasculature phenotype
Authors: Zvirblyte Justina , Nainys Juozas , Juzenas Simonas , Kubiliute Raimonda , Kincius Marius , Ulys Albertas , Jarmalaite Sonata , Mazutis Linas
Published: August 2023

Clear cell renal cell carcinoma (ccRCC) is the most prevalent form of renal cancer, accounting for over 75% of cases. The asymptomatic nature of the disease contributes to late-stage diagnoses and poor survival. Highly vascularized and immune infiltrated microenvironment are prominent features of ccRCC, yet the interplay between vasculature and immune cells, disease progression and response to therapy remains poorly understood. Using droplet-based single-cell RNA sequencing we profiled 50,236 transcriptomes from paired tumor and healthy adjacent kidney tissues. Our analysis revealed significant heterogeneity and inter-patient variability of the tumor microenvironment. Notably, we discovered a previously uncharacterized vasculature subpopulation associated with epithelial-mesenchymal transition. The cell-cell communication analysis revealed multiple modes of immunosuppressive interactions within the tumor microenvironment, including clinically relevant interactions between tumor vasculature and stromal cells with immune cells. The upregulation of the genes involved in these interactions was associated with worse survival in the TCGA KIRC cohort. Our findings demonstrate the role of tumor vasculature and stromal cell populations in shaping the ccRCC microenvironment and uncover a subpopulation of cells within the tumor vasculature that is associated with an invasive phenotype.
Signatures of internal feedback and trajectory control during goal-directed finger and whole-arm reaching movements
Authors: Chakrabhavi Niranjan , Varadhan SKM , Ghosal Ashitava , Murthy Aditya
Published: August 2023

Goal-directed behaviors involve the execution of a variety of eye, hand, and finger movements that follow invariant kinematics consisting of straight-line trajectories and bell-shaped velocity profiles. Despite the presence of neuromotor noise and distinct biomechanics such motions are performed with ease and reasonable accuracy. A fundamental unresolved issue in the field is to determine and delineate the extent to which these trajectories are planned or whether they are a consequence of trajectory-free online control. In this study, we address this question using Spearman’s rank correlation, zero-crossing rate andz-scores and analyze within-trial variability to investigate differences in the time evolution of trajectories during the presence or absence of a goal in finger and whole-arm reaching movements. We found that the central nervous system (CNS) implements control to follow an average trajectory, where goal-directed movements show an enhanced degree of trajectory control. Further, by performing the analysis on the actual timing, we found behavioral signatures of rapid control that might operate on these planned trajectories as early as 30 ms in finger movements and 16.67 ms in whole-arm reaching movements which are too early for trajectory control to be derived from delayed sensory feedback. The analysis also revealed that the controller gains varied along the movement and peaked distinctly at an early (20 %) and a late (90 %) phases of movement, suggesting that trajectory control may be accomplished through virtual way-point objectives during the execution of the movement.

Significance Statement

The extent to which reaching movements reflect the unfolding of a prespecified trajectory plan or whether they arise from a trajectory-free online control has remained a vexing issue for motor theorists. Using novel measures of control during the movement such as Spearman’s rank correlation, zero-crossing rate and trends inz-scores, we investigated goal-directed finger and whole-arm reaching movements and demonstrated that the CNS implements rapid control to follow a planned trajectory, especially during early and late phases of movement. Our results provide novel constraints for computational theories of motor control.
Resting-state EEG recorded with gel-based versus consumer dry electrodes: spectral characteristics and across-device correlations
Authors: Kleeva Daria , Ninenko Ivan , Lebedev Mikhail
Published: August 2023

Recordings of electroencephalographic (EEG) rhythms and their analyses have been instrumental in basic Neuroscience, clinical diagnostics, and the field of brain-computer interfaces (BCIs). While in the past such measurements have been conducted mostly in laboratory settings, recent advancements in dry electrode technology pave way to a broader range of consumer and medical application because of their greater convenience compared to gel-based electrodes. Here we conducted resting-state EEG recordings in two groups of healthy participants using three dry-electrode devices, the Neiry Headband, the Neiry Headphones and the Muse Headband, and one standard gel electrode-based system, the NVX. We examined signal quality for various spatial and spectral ranges which are essential for cognitive monitoring and consumer applications. Distinctive characteristics of signal quality were found, with the Neiry Headband showing sensitivity in low-frequency ranges and replicating the modulations of delta, theta and alpha power corresponding to the eyes-open and eyes-closed conditions, and the NVX system performing well in capturing high-frequency oscillations. The Neiry Headphones were more prone to low-frequency artifacts compared to the Neiry Headband, yet recorded modulations in alpha power and had a strong alignment with the NVX at higher frequencies. The Muse Headband had several limitations in signal quality. We suggest that while dry-electrode technology appears to be appropriate for the EEG rhythm-based applications the potential benefits of these technologies in terms of ease of use and accessibility should be carefully weighted against the capacity of each concrete system.
DiPPI: A curated dataset for drug-like molecules in protein-protein interfaces
Authors: Cankara Fatma , Senyuz Simge , Sayin Ahenk Zeynep , Gursoy Attila , Keskin Ozlem
Published: August 2023

Proteins interact through their interfaces, and dysfunction of protein-protein interactions (PPIs) has been associated with various diseases. Therefore, investigating the properties of the drug-modulated PPIs and interface-targeting drugs is critical. Here, we present a curated large dataset for drug-like molecules in protein interfaces. We further present DiPPI (Drugs in Protein-Protein Interfaces), a two-module website to facilitate the search for such molecules and their properties by exploiting our dataset in drug repurposing studies. In the interface module of the website, we extracted several properties of interfaces, such as amino acid properties, hotspots, evolutionary conservation of drug-binding amino acids, and post-translational modifications of these residues. On the drug-like molecule side, we curated a list of drug-like small molecules and FDA-approved drugs from various databases and extracted those that bind to the interfaces. We further clustered the drugs based on their molecular fingerprints to confine the search for an alternative drug to a smaller space. Drug properties, including Lipinski’s rules and various molecular descriptors, are also calculated and made available on the website to guide the selection of drug molecules. Our dataset contains 534,203 interfaces for 98,632 proteins, of which 55,135 are detected to bind to a drug-like molecule. 2,214 drug-like molecules are deposited on our website, among which 335 are FDA-approved. DiPPI provides users with an easy-to-follow scheme for drug repurposing studies through its well-curated and clustered interface and drug data; and is freely available athttp://interactome.ku.edu.tr:8501.