bluuebunny/crossref_metadata_2025_split huggingface dataset:
AI-algorithm training and validation for endometrial CD138+ cells in infertility-associated conditions; polycystic ovary syndrome (PCOS) and recurrent implantation failure (RIF)
Authors: Lee Seungbaek , Arffman Riikka K. , Komsi Elina K. , Lindgren Outi , Kemppainen Janette A. , Metsola Hanna , Ahtikoski Anne , Kask Keiu , Saare Merli , Salumets Andres , Piltonen Terhi T. 
Published: December 2023

AbstractImmunohistochemical analysis of CD138+ plasma cells has been applied for detecting endometrial inflammation, especially chronic endometritis (CE). In this study, we developed for the first time an artificial intelligence (AI) algorithm, AITAH, to identify CD138+ plasma cells within endometrial tissue, focusing on two infertility-related conditions: polycystic ovary syndrome (PCOS) and recurrent implantation failure (RIF). We obtained 193 endometrial tissues from healthy controls (n=73), women with PCOS (n=91), and RIF patients (n=29) and compared CD138+ cell percentages across cycle phases, ovulation status, and endometrial receptivity. We trained AITAH with CD138 stained tissue images, and experienced pathologists validated the training and performance of AITAH. AITAH, with high accuracy in detecting CD138+ cells (88.57%), revealed higher CD138+ cell percentages in the proliferative phase than in the secretory phase or in the anovulatory PCOS endometrium, irrespective of PCOS diagnosis. Interestingly, CD138+ percentages differed according to PCOS phenotype in the proliferative phase (p=0.01). Different receptivity statuses had no impact on the cell percentages in RIF samples. In summary, the AI-enabled analysis is a rapid and accurate tool to examine endometrial tissues, potentially aiding clinical decision-making. Here, the AI analysis demonstrated cycle-phase differences in CD138+ aggregations pattern, but no major alterations in PCOS or RIF samples.
A Video Intervention to Improve Patient Understanding of Tumor Genomic Testing in Patients with Cancer
Authors: Veney Deloris , Wei Lai , Toland Amanda E. , Presley Carolyn J. , Hampel Heather , Padamsee Tasleem J. , Lee Clara N. , Irvin William J. , Bishop Michael , Kim James , Hovick Shelly R. , Senter Leigha , Stover Daniel G. 
Published: December 2023

ABSTRACTBackgroundTumor genomic testing (TGT) has become standard-of-care for most patients with advanced/metastatic cancer. Despite established guidelines, patient education prior to TGT is variable or frequently omitted. The purpose of this study was to evaluate the impact of a concise (3-4 minute) video for patient education prior to TGT.MethodsBased on a quality improvement cycle, an animated video was created to be applicable to any cancer type, incorporating culturally diverse images, available in English and Spanish. Patients undergoing standard-of care TGT were enrolled at a tertiary academic institution and completed validated survey instruments immediately prior to video viewing (T1) and immediately post-viewing (T2). Instruments included: 1) 10-question objective genomic knowledge/understanding; 2) 10-question video message-specific knowledge/recall; 3) 11-question Trust in Physician/Provider; 4) attitudes regarding TGT. The primary objective was change in outcomes from before to after the video was assessed with Wilcoxon signed rank test.ResultsFrom April 2022 to May 2023, a total of 150 participants were enrolled (MBC n=53, LC n=38, OC n=59). For the primary endpoint, there was a significant increase in video message-specific knowledge (median 10 point increase; p<0.0001) with no significant change in genomic knowledge/understanding (p=0.89) or Trust in Physician/Provider (p=0.59). Results for five questions significantly improved, including the likelihood of TGT impact on treatment decision, incidental germline findings, and cost of testing. Improvement in video message-specific knowledge was consistent across demographic groups, including age, income, and education. Individuals with less educational attainment had had greater improvement from before to after video viewing.ConclusionsA concise, 3-4 minute, broadly applicable video incorporating culturally diverse images administered prior to TGT significantly improved video message-specific knowledge across all demographic groups. This resource is publicly available athttp://www.tumor-testing.com, with a goal to efficiently educate and empower patients regarding TGT while addressing guidelines within the flow of clinical practice.Clinical Trial RegistrationClinicalTrials.govNCT05215769
Higher loss of livelihood and impoverishment in households affected by tuberculosis compared to non-tuberculosis affected households in Zimbabwe: a cross-sectional study
Authors: Timire Collins , Houben Rein MGJ , Pedrazzoli Debora , Ferrand Rashida Abbas , Calderwood Claire J , Bond Virginia , Mbiba Fredrick , Kranzer Katharina 
Published: December 2023

AbstractIntroductionTuberculosis (TB) disproportionally affects poor people, leading to income and non-income losses. Measures of socioeconomic impact of TB, e.g. impoverishment and patient costs are inadequate to capture non-income losses. We applied impoverishment and a multidimensional measure on TB and non-TB affected households in Zimbabwe.MethodsWe conducted a cross-sectional study in 270 households: 90 non-TB; 90 drug-susceptible TB (DS-TB), 90 drug-resistant TB (DR-TB) during the COVID-19 pandemic (2020-2021). Household data included ownership of assets, number of household members, income and indicators on five capital assets: financial, human, social, natural and physical. We determined proportions of impoverished households for periods 12 months prior and at the time of the interview. Households with incomes below US$1.90/day were considered to be impoverished. We used principal component analysis on five capital asset indicators to create a binary outcome variable indicating loss of livelihood. Log-binomial regression was used to determine associations between loss of livelihood and type of household.ResultsTB-affected households reported higher previous episodes of TB and household members requiring care than non-TB households. Households that were impoverished 12 months prior to the study were: 21 non-TB (23%); 40 DS-TB (45%); 37 DR-TB (41%). The proportions increased to 81%, 88% and 94%, respectively by the time of interview. Overall, 56% (152/270) of households sold assets: 44% (40/90) non-TB, 58% (52/90) DS-TB and 67% (60/90) DR-TB. Children’s education was affected in 31% (56/180) of TB-affected compared to 13% (12/90) non-TB households. Overall, 133(50%) households experienced loss of livelihood, with TB-affected households twice as likely to experience loss of livelihood; adjusted prevalence ratio (aPR=2.02 (95%CI:1.35-3.03)). The effect of TB on livelihood was most pronounced in poorest households (aPR=2.64, (95%CI:1.29-5.41)).ConclusionsTB-affected households experienced greater socioeconomic losses compared to non-TB households. Multidimensional measures of TB are crucial to inform multisectoral approaches to mitigate impacts of TB and other shocks.
Comprehensive profiling of social mixing patterns in resource poor countries: a mixed methods research protocol
Authors: Aguolu Obianuju Genevieve , Kiti Moses Chapa , Nelson Kristin , Liu Carol Y. , Sundaram Maria , Gramacho Sergio , Jenness Samuel , Melegaro Alessia , Sacoor Charfudin , Bardaji Azucena , Macicame Ivalda , Jose Americo , Cavele Nilzio , Amosse Felizarda , Uamba Migdalia , Jamisse Edgar , Tchavana Corssino , Briones Herberth Giovanni Maldonado , Jarquín Claudia , Ajsivinac María , Pischel Lauren , Ahmed Noureen , Mohan Venkata Raghava , Srinivasan Rajan , Samuel Prasanna , John Gifta , Ellington Kye , Joaquim Orvalho Augusto , Zelaya Alana , Kim Sara , Chen Holin , Kazi Momin , Malik Fauzia , Yildirim Inci , Lopman Benjamin , Omer Saad B. 
Published: December 2023

ABSTRACTBackgroundLow-and-middle-income countries (LMICs) bear a disproportionate burden of communicable diseases. Social interaction data inform infectious disease models and disease prevention strategies. The variations in demographics and contact patterns across ages, cultures, and locations significantly impact infectious disease dynamics and pathogen transmission. LMICs lack sufficient social interaction data for infectious disease modeling.MethodsTo address this gap, we will collect qualitative and quantitative data from eight study sites (encompassing both rural and urban settings) across Guatemala, India, Pakistan, and Mozambique. We will conduct focus group discussions and cognitive interviews to assess the feasibility and acceptability of our data collection tools at each site. Thematic and rapid analyses will help to identify key themes and categories through coding, guiding the design of quantitative data collection tools (enrollment survey, contact diaries, exit survey, and wearable proximity sensors) and the implementation of study procedures.We will create three age-specific contact matrices (physical, nonphysical, and both) at each study site using data from standardized contact diaries to characterize the patterns of social mixing. Regression analysis will be conducted to identify key drivers of contacts. We will comprehensively profile the frequency, duration, and intensity of infants’ interactions with household members using high resolution data from the proximity sensors and calculating infants’ proximity score (fraction of time spent by each household member in proximity with the infant, over the total infant contact time) for each household member.DiscussionOur qualitative data yielded insights into the perceptions and acceptability of contact diaries and wearable proximity sensors for collecting social mixing data in LMICs. The quantitative data will allow a more accurate representation of human interactions that lead to the transmission of pathogens through close contact in LMICs. Our findings will provide more appropriate social mixing data for parameterizing mathematical models of LMIC populations. Our study tools could be adapted for other studies.
Impact of electronic medical records on healthcare delivery in Nigeria: A Review
Authors: Olukorode Oreoluwa , Adedeji Oluwakorede Joshua , Adetokun Adetayo , Abioye Ajibola Ibraheem 
Published: December 2023

AbstractElectronic medical records (EMRs) have great potential to improve healthcare processes and outcomes. They are increasingly available in Nigeria, as in many developing countries. The impact of their introduction has not been well studied. We sought to synthesize the evidence from primary studies of the effect of EMRs on data quality, patient-relevant outcomes and patient satisfaction. We identified and examined five original research articles published up to May 2023 in the following medical literature databases: PUBMED/Medline, EMBASE, Web of Science, African Journals Online and Google Scholar. Four studies examined the influence of the introduction of or improvements in the EMR on data collection and documentation. The pooled percentage difference in data quality after introducing or improving the EMR was 142% (95% CI: 82% to 203%,p-value < 0.001). There was limited heterogeneity in the estimates (I2= 0%,p-heterogeneity = 0.93) and no evidence suggestive of publication bias. The 5thstudy assessed patient satisfaction with pharmacy services following the introduction of the EMR but neither had a comparison group nor assessed patient satisfaction before EMR was introduced. We conclude that the introduction of EMR in Nigerian healthcare facilities meaningfully increased the quality of the data.Author SummaryElectronic medical records, or EMRs, offer the potential to improve healthcare in many developing nations, including Nigeria. The actual impact of these digital records hasn’t gotten enough attention, despite their growing availability. Our goal in doing this review was to compile and evaluate primary study data on the effects of EMRs on patient satisfaction, patient-related outcomes, and data quality in Nigeria. After searching through medical literature databases, we found five original research publications up to May 2023 that were suitable for our study. The impact of EMR implementation or upgrades on data collection and documentation was examined in four of these studies, while patient satisfaction with pharmacy services following EMR adoption was evaluated in the fifth study. Although the included studies did not quantitatively assess the impact of EMR adoption on patient satisfaction, we were able to conclude from the studies that the introduction of EMR in Nigerian healthcare facilities meaningfully increased the quality of the data
Non-communicable diseases Prevalence by HIV Status in East Africa: A protocol for a systematic review and Meta-analysis
Authors: Kasango Asani , Daama Alex , Negesa Lilian 
Published: December 2023

AbstractIntroductionOver the past decade, HIV care and treatment programs have grown exponentially, resulting in improved survival among persons living with HIV. In the same period, the prevalence of non-communicable diseases has been reported to be higher among people living with HIV as compared to their HIV-negative counterparts. In this review, we aim to assess the prevalence of non-communicable diseases stratified by HIV status in East Africa.MethodsWe plan to assess observational studies especially case-control, cohort, and cross-sectional studies and clinical trials. These studies will be related to non-communicable diseases and done in East Africa. This review will be for studies done in East Africa from 1stJan 2013 to 31stDec 2023. The team will search databases such as East African Medical Journal, PubMed, Pan African Medical Journal, Scopus, African Health Sciences Journal, African Index, Medicus, and African Journals Online among others. We will use subheadings such as HIV, NCDs, and East Africa to search for relevant Journals. The I2will be used to assess the heterogeneity of individual studies. All statistical analyses will be performed in STATA V15, and results will be graphically presented on a forest plot.DiscussionWith the rising burden of non-communicable diseases globally, there is much to learn whether the prevalence differs by HIV status or not.
Transcription attenuation in synthetic promoters in tandem formation
Authors: Chauhan Vatsala , Baptista Ines S. C. , Jagadeesan Rahul , Dash Suchintak , Ribeiro Andre S. 
Published: December 2023

ABSTRACTClosely spaced promoters are ubiquitous in prokaryotic and eukaryotic genomes. How their structure and dynamics relate remains unclear, particularly for tandem formations. To study their transcriptional interference, we engineered two pairs and one trio of synthetic promoters in non-overlapping, tandem formation, in single-copy plasmids. Fromin vivomeasurements inE. colicells, we found that promoters in tandem formation have attenuated transcription rates. The attenuation strength can be widely fine-tuned by the promoters’ positioning, natural regulatory mechanisms, and other factors, including the antibiotic rifampicin, which hampers RNAP promoter escape. From this, and supported by in silico models, we concluded that the attenuation emerges from premature terminations generated by collisions between RNAPs elongating from upstream promoters and RNAPs occupying downstream promoters. Moreover, we found that these collisions can cause one or both RNAPs to fall-off. The broad spectrum of possible, externally regulated, attenuation strengths in synthetic tandem promoters should make these structures valuable internal regulators of future synthetic circuits.
Distinct secretomes in p16- and p21- positive senescent cells across tissues
Authors: Saul Dominik , Jurk Diana , Doolittle Madison L. , Kosinsky Robyn Laura , Monroe David G , LeBrasseur Nathan K. , Robbins Paul D. , Niedernhofer Laura J. , Khosla Sundeep , Passos João F. 
Published: December 2023

SUMMARYSenescent cells drive age-related tissue dysfunction via the induction of a chronic senescence-associated secretory phenotype (SASP). The cyclin-dependent kinase inhibitors p21Cip1and p16Ink4ahave long served as markers of cellular senescence. However, their individual roles remain incompletely elucidated. Thus, we conducted a comprehensive examination of multiple single-cell RNA sequencing (scRNA-seq) datasets spanning both murine and human tissues during aging. Our analysis revealed that p21Cip1and p16Ink4atranscripts demonstrate significant heterogeneity across distinct cell types and tissues, frequently exhibiting a lack of co-expression. Moreover, we identified tissue-specific variations in SASP profiles linked to p21Cip1or p16Ink4aexpression. Our study underscores the extraordinary diversity of cellular senescence and the SASP, emphasizing that these phenomena are inherently cell- and tissue-dependent. However, a few SASP factors consistently contribute to a shared “core” SASP. These findings highlight the need for a more nuanced investigation of senescence across a wide array of biological contexts.
Single-molecule imaging reveals a direct role of CTCF’s zinc fingers in SA interaction and cluster-dependent RNA recruitment
Authors: Huber Jonas , Tanasie Nicoleta-Loredana , Zernia Sarah , Stigler Johannes 
Published: December 2023

AbstractCTCF is a zinc finger protein associated with transcription regulation that also acts as a barrier factor for topologically associated domains (TADs) generated by cohesin via loop extrusion. These processes require different properties of CTCF-DNA interaction, and it is still unclear how CTCF’s structural features may modulate its diverse roles. Here, we employ single-molecule imaging to study both full-length CTCF and truncation mutants. We show that CTCF enriches at CTCF binding sites (CBSs), displaying a longer lifetime than observed previously. We demonstrate that the zinc finger domains mediate CTCF clustering and that clustering enables RNA recruitment, possibly creating a scaffold for interaction with RNA-binding proteins like cohesin’s subunit SA. We further reveal a direct recruitment and an increase of SA residence time by CTCF bound at CBSs, suggesting that CTCF-SA interactions are crucial for cohesin stability on chromatin at TAD borders. Furthermore, we establish a single-molecule transcription assay and show that although a transcribing polymerase can remove CTCF from CBSs, transcription is impaired. Our study shows that context-dependent nucleic acid binding determines the multifaceted CTCF roles in genome organization and transcription regulation.
Biodegradable silica nanoparticles for efficient linear DNA gene delivery
Authors: Ramos-Valle Andrés , Kirst Henning , Fanarraga Mónica L. 
Published: December 2023

AbstractTargeting, safety, scalability, and storage stability of vectors are still challenges in the field of nucleic acid delivery for gene therapy. Silica-based nanoparticles have been widely studied as gene carriers, exhibiting key features such as biocompatibility, simplistic synthesis and enabling easy surface modifications for targeting. However, the ability of the formulation to incorporate DNA is limited, which restricts the number of DNA molecules that can be incorporated into the particle, thereby reducing gene expression.Here we use polymerase chain reaction (PCR)-generated linear DNA molecules to augment the coding sequences of gene-carrying nanoparticles, thereby maximizing nucleic acid loading and minimizing the size of these nanocarriers. This approach results in a remarkable 16-fold increase in protein expression six days post-transfection in cells transfected with particles carrying the linear DNA compared with particles bearing circular plasmid DNA. The study also showed that the use of linear DNA entrapped in DNA@SiO2resulted in a much more efficient level of gene expression compared to standard transfection reagents. The system developed in this study features simplicity, scalability, and increased transfection efficiency and gene expression over existing approaches, enabled by improved embedment capabilities for linear DNA, compared to conventional methods such as lipids or polymers, which generally show greater transfection efficiency with plasmid DNA. Therefore, this novel methodology can find applications not only in gene therapy but also in research settings for high throughput gene expression screenings.
Multi-variate statistical and machine learning reveals the interplay between sex and age in antibody responses tode novoSARS-CoV-2 infection and vaccination
Authors: Cuperlovic-Culf Miroslava , Bennett Steffany , Galipeau Yannick , McCluskie Pauline S. , Arnold Corey , Bagheri Salman , Cooper Curtis L. , Langlois Marc-André , Fritz Jörg , Piccirillo Ciriaco A. , Crawley Angela M. 
Published: December 2023

SummaryPrevention of negative COVID19 infection outcomes and infection/vaccine-acquired immunity is associated with the quality of antibody responses, whose variance by age and sex are poorly understood. Integrated, network approaches, identified sex and age effects in antibody responses and neutralization potential ofde novoinfection and vaccination throughout the Covid-19 pandemic. Cluster analysis found neutralization values followed SARS-CoV-2 specific receptor binding RIgG, spike SIgG and S and RIgA levels based on COVID19 status. Stochastic behavior tests and other analytical methods revealed sex differences only in persons <40y.o. Serum IgA antibody titers correlated with neutralization only in females 40-60y.o. Network analysis found males could improve IgA responses after vaccination dose 2, unlike >60y.o. females. Complex correlation analyses found vaccination induced less antibody isotype switching and neutralization in older persons, especially in females. Sex dependent antibody & neutralization behavior decayed fastest in older males and with vaccination. Such sex and age characterization by machine learning can direct studies integrating cell mediated responses to define yet elusive correlates of protection and inform age and sex precision-focused vaccine design.