bluuebunny/crossref_metadata_2025_split huggingface dataset:
Empowering High Throughput Screening of 3D Models: Automated Dispensing of Cervical and Endometrial Cancer Cells
Authors: Seymour Samantha , Cadena Ines , Johnson Mackenzie , Jenne Molly , Adem Iman , Almer Alyssa , Frankovic Rachel , Spence Danielle , Haddadin Andrea , Fogg Kaitlin C. 
Published: March 2024

PurposeCervical and endometrial cancers pose significant challenges in women’s healthcare due to their high mortality rates and limited treatment options. High throughput screening (HTS) of cervical and endometrial cancerin vitromodels offer a promising avenue for drug repurposing and broadening patient treatment options. Traditional two-dimensional (2D) cell-based screenings have limited capabilities to capture crucial multicellular interactions, that are improved upon in three dimensional (3D) multicellular tissue engineered models. However, manual fabrication of the 3D platforms is both time consuming and subject to variability. Thus, the goal of this study was to utilize automated cell dispensing to fabricate 3D cell-based HTS platforms using the HP D100 Single Cell Dispenser to dispense cervical and endometrial cancer cells.MethodsWe evaluated the effects of automated dispensing of the cancer cell lines by tuning the dispensing protocol to align with cell size measured in solution and the minimum cell number for acceptable cell viability and proliferation. We modified our previously reported coculture models of cervical and endometrial cancer to be in a 384 well plate format and measured microvessel length and cancer cell invasion.ResultsAutomatically and manually dispensed cells were directly compared revealing minimal differences between the dispensing methods. These findings suggest that automated dispensing of cancer cells minimally affects cell behavior and can be deployed to decreasein vitromodel fabrication time.ConclusionsBy streamlining the manufacturing process, automated dispensing holds promise for enhancing efficiency and scalability of 3Din vitroHTS platforms, ultimately contributing to advancement in cancer research and treatment.
Exploring the mitochondrial genomes and phylogenetic relationships of eleven Bryconidae species
Authors: Márquez Edna J. , Gómez-Chavarría Daniel A. , Alzate Juan F. 
Published: March 2024

AbstractComparative mitogenomics and its evolutionary relationships within Bryconidae remains largely unexplored. To bridge this gap, this study assembled 15 mitogenomes from 11 Bryconidae species, including five newly sequenced.Salminusmitogenomes, exceeding 17,700 bp, exhibited the largest size, contrasting with a median size of 16,848 bp in the remaining species (BryconandChilobrycon). These mitogenomes encode 37 typical mitochondrial genes, including 13 protein-coding, 2 ribosomal RNA, and 22 transfer RNA genes, and exhibit the conserved gene arrangement found in most fish species. Phylogenetic relationships, based on the maximum-likelihood method, revealed that the trans-Andean species (found in northwestern South America) clustered into two main sister clades. One clade comprised the trans-Andean species from the Pacific slope,Brycon chagrensisandChilobrycon deuterodon. The other clade grouped the trans-Andean species from the Magdalena-Cauca Basin with their cis-Andean congeners (found in eastern South America), withBrycon rubricaudaas its sister clade. The lack of monophyly within these genera indicates that the systematic classification of Bryconidae requires further examination. This study provides novel insights into mitogenome characteristics and evolutionary pathways within Bryconidae, standing as crucial information for prospective phylogenetic and taxonomic studies, molecular ecology, and provides a valuable resource for environmental DNA applications.
On the identification of differentially-active transcription factors from ATAC-seq data
Authors: Gerbaldo Felix Ezequiel , Sonder Emanuel , Fischer Vincent , Frei Selina , Wang Jiayi , Gapp Katharina , Robinson Mark D. , Germain Pierre-Luc 
Published: March 2024

AbstractATAC-seq has emerged as a rich epigenome profiling technique, and is commonly used to identify Transcription Factors (TFs) underlying given phenomena. A number of methods can be used to identify differentially-active TFs through the accessibility of their DNA-binding motif, however little is known on the best approaches for doing so. Here we benchmark several such methods using a combination of curated datasets with various forms of short-term perturbations on known TFs, as well as semi-simulations. We include both methods specifically designed for this type of data as well as some that can be repurposed for it. We also investigate variations to these methods, and identify three particularly promising approaches (a chromVAR-limma workflow with critical adjustments, monaLisa and a combination of GC smooth quantile normalization and multivariate modeling). We further investigate the specific use of nucleosome-free fragments, the combination of top methods, and the impact of technical variation. Finally, we illustrate the use of the top methods on a novel dataset to characterize the impact on DNA accessibility of TRAnscription Factor TArgeting Chimeras (TRAFTAC), which can deplete TFs – in our case NFkB – at the protein level.Author summaryTranscription factors regulate gene expression by binding sites in the genome that often harbor a specific DNA motif. The collective accessibility of these motif-matching regions, measured by technologies such as ATAC-seq, can be used to infer the activity of the corresponding transcription factors. Here we use curated datasets of 11 TF-specific perturbations as well as 116 semi-simulated datasets to benchmark various methods for identifying factors that differ in activity between experimental conditions. We investigate important variations in the analysis and make recommendations pertaining to such analysis. Finally, we illustrate the application of the top methods to characterize the effects of a novel method for perturbing transcription factors at the protein level.
Harnessing digital tools for the management of large-scale larviciding operations: a pilot of the ZzappMalaria software system in Obuasi, Ghana
Authors: Williams Ignatius , Desewu Kwame , Asiedu Samuel , Ato Egyir Nicholas , Gluck Dan , Houri-Yafin Arnon , Fialkoff Yonata , Vigodny Arbel 
Published: March 2024

AbstractLarval source management (LSM) has played a critical role in historical malaria elimination endeavors, yet its application in tropical settings has been hampered by operational hurdles and limited effectiveness. To address these issues, ZzappMalaria Ltd. developed a digital platform for the planning and implementation of LSM campaigns, the features and field efficacy of which are discussed in this paper.Piloted in collaboration with AngloGold Ashanti Malaria Control Ltd. (AGAMal) in Obuasi, Ghana, the system, comprising a planning tool, a mobile app for fieldworkers and an online dashboard for monitoring and worker management, facilitated the detection of more than 4,000 water bodies and reduced the mosquito population by 62% for a cost of $0.24 per person protected (PPP). The data available does not provide sufficient evidence to conclusively determine whether a reduction in malaria cases occurred; nevertheless, the results underscore the potential of digitization to surmount the operational challenges of large-scale LSM campaigns.
Artificial intelligence-generated smart impression from 9.8-million radiology reports as training datasets from multiple sites and imaging modalities
Authors: Kaviani Parisa , Kalra Mannudeep K. , Digumarthy Subba R , Rodriguez Karen , Agarwal Sheela , Brooks Rupert , En Sovann , Alkasab Tarik , Bizzo Bernardo C. , Dreyer Keith J. 
Published: March 2024

AbstractImportanceAutomatic generation of the impression section of radiology report can help make radiologists efficient and avoid reporting errors.ObjectiveTo evaluate the relationship, content, and accuracy of an Powerscribe Smart Impression (PSI) against the radiologists’ reported findings and impression (RDF).Design, Setting, and ParticipantsThe institutional review board approved retrospective study developed and trained an PSI algorithm (Nuance Communications, Inc.) with 9.8 million radiology reports from multiple sites to generate PSI based on information including the protocol name and the radiologists-dictated findings section of radiology reports. Three radiologists assessed 3879 radiology reports of multiple imaging modalities from 8 US imaging sites. For each report, we assessed if PSI can accurately reproduce the RDF in terms of the number of clinically significant findings and radiologists’ style of reporting while avoiding potential mismatch (with the findings section in terms of size, location, or laterality). Separately we recorded the word count for PSI and RDF. Data were analyzed with Pearson correlation and paired t-tests.Main Outcomes and MeasuresThe data were ground truthed by three radiologists. Each radiologists recorded the frequency of the incidental/significant findings, any inconsistency between the RDF and PSI as well as the stylistic evaluation overall evaluation of PSI. Area under the curve (AUC), correlation coefficient, and the percentages were calculated.ResultsPSI reports were deemed either perfect (91.9%) or acceptable (7.68%) for stylistic concurrence with RDF. Both PSI (mismatched Haller’s Index) and RDF (mismatched nodule size) had one mismatch each. There was no difference between the word counts of PSI (mean 33±23 words/impression) and RDF (mean 35±24 words/impression) (p>0.1). Overall, there was an excellent correlation (r= 0.85) between PSI and RDF for the evolution of findings (negative vs. stable vs. new or increasing vs. resolved or decreasing findings). The PSI outputs (2%) requiring major changes pertained to reports with multiple impression items.Conclusion and RelevanceIn clinical settings of radiology exam interpretation, the Powerscribe Smart Impression assessed in our study can save interpretation time; a comprehensive findings section results in the best PSI output.
Pattern, treatment modalities and radiological outcome of pediatric femoral shaft fractures treated in Northern,Tanzania
Authors: Kilawa Shindo I. , Pallangyo Anthony J. , Maya Elifuraha G. , Temu Rogers J. , Mandari Faiton N. , Olotu Frank I. , Ofunguo Estomick K. , Sadiq Adnan M. , Massawe Honest H. , Shirima Octavian , Shoo Reginald 
Published: March 2024

AbstractBackgroundFemoral shaft fracture is among the most common causes of paediatric hospitalisation, mortality and morbidity worldwide. There is no clear option that is preferable to other treatment modalities, especially between 5 to 16 years and published studies are scarce on radiological outcomes in Sub-Saharan Africa.This study aimed to determine the pattern, treatment modalities and radiological outcome of the paediatric femoral fractures treated at KCMC.MethodologyA cross-sectional study was conducted for all children with femoral shaft fractures treated at Kilimanjaro Christian Medical Centre from 1stJanuary 2018 to 31stDecember 2022. The approval to conduct the research was obtained from Kilimanjaro College Research Ethics and Review Committee (CRERC) with ethical clearance Reg NO PG 88/2022. In our study we used secondary data and the permission to conduct the research was obtained from KCMC, hence no formal consent was required from patients/parents.The data was accessed from the files and Elecronic Health Management system (EHMS) from 01/04/2023 to 31/07/2023.The radiological outcome; shortening, angulations in six weeks and fracture union, 12 weeks post-management were reviewed with the involvement of a consultant radiologist and the orthopaedic surgeon to obtain the precise information and were recorded on the extraction sheet.ResultsThis study included 230 study participants who met the inclusion criteria. The mean age of participants was 9.1 (5.1) years, 41.3%, was aged 6 – 12 years, 82.2% were males, 45.7% were involved in a MTC, and 83.5% had no health insurance. The commonest fracture type was 92.6% closed, 48.7% transverse, and 65.% right side. Non-operatively was used in 50.9% of which 76.8% were treated with late hip Spica. Of those treated operatively, 61.1% were plating.The majority had good radiological outcomes with acceptable solid union, angulation and shortening. Those patients who were not operated had 94% lower odds of satisfactory radiological outcomes than those who were operated ( AOR=0.06, 95% CI: 0.01 – 0.27 and p<0.001) whereas other factors were not statistically significant.ConclusionThe majority of the study participants were male and were involved in MTC as the commonest mechanism of injury. Most had closed fractures that mainly presented on the right side and transverse fractures were the most common type. The hip Spica was common non-operatively option; however, plating was the most common operative option. Treatment modality substantially affected radiological outcomes and was statistically significant.
The Relationship Between Neighborhood Safety, Paternal Presence and Somatic Symptoms of Dissociation in Children
Authors: Pacelli Jenna 
Published: March 2024

AbstractIntroductionChild exposure to prolonged stressful home environments can lead to life-long patterns that are later misdiagnosed in adulthood as anxiety disorders, ADHD and depressive disorders, among others. In theory, paternal involvement and neighborhood safety are strong buffers against toxic stress and therefore dissociative symptoms in children. The relationship between paternal involvement and rates of violence in the neighborhood and rates of dissociative symptoms in children are not yet fully understood. This study investigates the relationship between paternal involvement or neighborhood safety on somatic symptoms of dissociation in children.MethodsThis was a retrospective study based on the open-source dataset from Welfare, Children, and Families: A Three-City Study, Dataset 0005 (Angel et al., 2012). A cross-tab analysis investigated the relationship between 1) the likelihood of neighborhood assaults and 2) how often the child saw/spoke to their father in the last year with the likelihood of a child having a) concentration issues, b) confusion, c) being lost in thought, d) hearing voices and e) staring blankly.ResultsResults show that children who lived in neighborhoods where there were more muggings and assaults were more likely to be staring blankly and have concentration problems. Children who saw or talked to their father less were more likely to have concentration problems. Lastly, children who saw their fathers less often were more likely to hear voices that were not there.ConclusionThis study showed a relationship between rates of violence in the neighborhood and paternal presence and symptoms of dissociation in children. This suggests that the lived experience of the child affects their cognition and can be impacted by living in unsafe areas and not being able to see or speak with their father. Dissociative symptoms are linked with an increased risk of substance abuse, suicide attempts, heart disease, cancer, and skeletal fractures. Understanding factors that affect dissociation will provide opportunities to prevent childhood dissociation.
ASSESSING THE NET FINANCIAL BENEFITS OF EMPLOYING DIGITAL ENDPOINTS IN CLINICAL TRIALS
Authors: DiMasi Joseph A. , Dirks Abigail , Smith Zachary , Valentine Sarah , Goldsack Jennifer C. , Metcalfe Thomas , Grewal Upinder , Leyens Lada , Conradi Ute , Karlin Daniel , Maloney Lesley , Getz Kenneth A. , Hartog Bert 
Published: March 2024

ABSTRACTBackgroundIn the last few decades developers of new drugs, biologics, and devices have increasingly leveraged digital health technologies (DHTs) to assess clinical trial digital endpoints. To our knowledge, a comprehensive assessment of the financial net benefits of digital endpoints in clinical trials has not been conducted.Data and MethodsWe obtained data from the Digital Medicine Society (DiMe) Library of Digital Endpoints and the U.S. clinical trials registry, ClinicalTrials.gov. The benefit metrics are changes in trial phase duration and enrollment associated with the use of digital endpoints. The cost metric was obtained from an industry survey of the costs of including digital endpoints in clinical trials. We developed an expected net present value (eNPV) model of the cash flows for new drug development and commercialization to assess financial value. The value measure is the increment in eNPV that occurs when digital endpoints are employed. We also calculated a return on investment (ROI) as the ratio of the estimated increment in eNPV to the mean digital endpoint implementation cost.ResultsFor phase 2 trials, the increase in eNPV varied from $2.2 million to $3.3 million, with ROIs between 32% to 48% per indication. The net benefits were substantially higher for phase 3 trials, with the increase in eNPV varying from $27 million to $48 million, with ROIs that were four to seven times the investment.ConclusionsThe use of digital endpoints in clinical trials can provide substantial extra value to sponsors developing new drugs, with high ROIs.
Neurofilament light and glial fibrillary acidic protein in mood and anxiety disorders: A systematic review and meta-analysis
Authors: Kang Matthew JY , Grewal Jasleen , Eratne Dhamidhu , Malpas Charles , Chiu Wei-Hsuan , Katisko Kasper , Solje Eino , Santillo Alexander F , Mitchell Philip B. , Hopwood Malcolm , Velakoulis Dennis 
Published: March 2024

AbstractBackgroundNeurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are biomarkers of neuronal injury measurable in cerebrospinal fluid (CSF) and blood. Despite their potential as diagnostic tests for neurodegenerative disorders, it is unclear how they behave in mood and anxiety disorders. We conducted a systematic review and meta-analysis to investigate whether NfL and GFAP concentrations were altered in adults with mood and anxiety disorders compared to healthy controls.MethodsThe study was prospectively registered on PROSPERO (CRD42023434617). We followed the PRISMA guidelines, searched PubMed, Web of Science, PsycINFO, MEDLINE and Embase up to the 31/05/2023, and assessed relevant studies and their risk of bias. The primary outcome was the standardised mean difference (SMD) and 95% confidence interval (95% CI) of NfL and GFAP concentrations, which was pooled using a random-effects model adopting the restricted maximum likelihood estimator.ResultsTwenty-one studies met inclusion criteria, comprising of 2327 individuals (695 major depression, 502 bipolar disorder, and 1130 controls). When we compared people with major depression and controls, there was no difference in NfL (SMD = 0.29; 95% CI: -0.10, 0.68) nor GFAP (SMD = 0.47; 95% CI: -0.74, 1.68). In people with bipolar disorder, NfL was significantly elevated compared to controls (SMD = 0.58; 95% CI: 0.16, 0.99). However, the subgroup analysis including more sensitive assay kits (blood Simoa and CSF ELISA), found no significant difference (SMD = 0.40; 95% CI: -0.04, 0.85). Only one study studied GFAP in bipolar disorder. No studies explored NfL nor GFAP concentrations in anxiety disorders.DiscussionWe found that NfL and GFAP concentrations were not elevated in depression. In bipolar disorder, NfL concentration was elevated, though not in the sensitivity analysis. Our study informs clinicians about how to interpret these emerging biomarkers in determining whether a person’s symptoms are caused by a neurodegenerative or mood disorder.
Effects of individual components of remote monitoring for implantable cardioverter defibrillators or cardiac resynchronisation therapy defibrillators: protocol for a systematic review and component network meta-analysis
Authors: Okazaki Makiko , Sekiguchi Natsuko , Sahashi Yuki , Noma Hisashi , Mihara Takahiro 
Published: March 2024

ABSTRACTIntroductionCurrently, the standard of care for patients with cardiac implantable electronic devices (CIEDs) such as implantable cardioverter-defibrillators (ICD) and cardiac resynchronisation therapy-defibrillators (CRT-D) involves a combination of in-person outpatient visits and remote monitoring (RM). RM consists of scheduled remote device interrogation and automated transmission of prespecified alerts (alert transmission) at varying frequencies depending on manufacturers and institutions. However, the effects of RM factors on prognosis remain unclear. This systematic review and component network meta-analysis (CNMA) will aim to investigate which RM components (device interrogation, alert transmission, and data transmission frequency) have the greatest impact on prognosis in patients with ICD or CRT-D.Methods and analysisA systematic review will be conducted using MEDLINE (PubMed), Embase, the Cochrane Central Register of Controlled Trials, the Web of Science, Clinical Trials.gov, the WHO International Clinical Trials Registry Platform (ICTRP), the European Union Clinical Trials Register (EU-CTR), and the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR). We will include randomised controlled trials (RCTs) assessing the effect of RM on patient outcomes in individuals with ICD or CRT-D. The primary outcome will be hospitalisation due to cardiovascular disease, heart failure, and device-related complications. Two authors will independently conduct literature screening, data extraction, and risk of bias assessment. Random-effects model pairwise meta-analysis, random-effects network meta-analysis (NMA), and additive CNMA will be applied in data synthesis. To assess the quality of evidence, we will employ the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach for pairwise meta-analysis and the Confidence in Network Meta-Analysis (CINeMA) approach for NMA.Ethics and disseminationEthics approval is not required as this study will use existing published data. The results will be submitted for publication in a peer-reviewed journal.PROSPERO registration numberCRD42024517406.
The Association between Active Membership in Voluntary Organizations and Homonegativity
Authors: Khanehpaza Amirhossein , Pongpirul Krit , Jeeyapant Atthanee 
Published: March 2024

AbstractHomonegativity adversely affects the health and well-being of homosexuals in society, making it vital to identify factors associated with it. This study investigates whether active membership in voluntary organizations correlates with homonegativity. We analyzed the latest World Values Survey dataset, spanning 2017 to 2022, which encompasses 63 countries. Our findings suggest that active membership in certain voluntary organizations correlates with homonegativity levels among both men and women across various age groups. Specifically, active participation in sports or recreational organizations, professional associations, art, music, or educational organizations, and humanitarian or charitable organizations was found to be negatively correlated with homonegativity in specific gender-age groups, albeit with varying degrees of association strength. We postulate that this correlation might hint at causation, suggesting that active membership in these organizations promotes greater tolerance towards homosexuals and homosexuality. Furthermore, our analysis indicates that demographic and socio-economic variables, the political freedom of the respondent’s country, and the respondent’s life satisfaction are also linked to homonegativity.