bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protocol for a phase 3, randomised, active-control study of four-factor prothrombin complex concentrate versus frozen plasma in bleeding adult cardiac surgery patients requiring coagulation factor replacement: the LEX-211 (FARES-II) trial
Authors: Karkouti Keyvan , Callum Jeannie , Bartoszko Justyna , Solomon Cristina , Knaub Sigurd , Levy Jerrold H , Tanaka Kenichi A 
Published: August 2024

IntroductionReduced thrombin generation is an important component of post cardiopulmonary bypass (CPB) coagulopathy. To replenish coagulation factors and enhance thrombin generation in bleeding surgical patients, frozen plasma (FP) and four-factor prothrombin complex concentrate (4F-PCC) are used. However, the efficacy–safety balance of 4F-PCC relative to FP in cardiac surgery is unconfirmed.Methods and analysisLEX-211 (FARES-II) is an active-control, randomised, phase 3 study comparing two coagulation factor replacement therapies in bleeding adult cardiac surgical patients at 12 hospitals in Canada and the USA. The primary objective is to determine whether 4F-PCC (Octaplex/Balfaxar, Octapharma) is clinically non-inferior to FP for haemostatic effectiveness. Inclusion criteria are any index (elective or non-elective) cardiac surgery employing CPB and coagulation factor replacement with 4F-PCC or FP ordered in the operating room for bleeding management. Patients will be randomised to receive 1500 or 2000 international units of 4F-PCC or 3 or 4 units of FP, depending on body weight. The primary endpoint of haemostatic treatment response is ‘effective’ if no additional haemostatic intervention is required from 60 min to 24 hours after the first initiation of 4F-PCC or FP; or ‘ineffective’ if any other haemostatic intervention (including a second dose of study drug) is required. An estimated 410 evaluable patients will be required to demonstrate non-inferiority (one-sided α of 0.025, power ≥90%, non-inferiority margin 0.10). Secondary outcomes include transfusions, bleeding-related clinical endpoints, coagulation parameters and safety.Ethics and disseminationThe trial has been approved by the institutional review boards of all participating centres. Trial completion is anticipated at the end of 2024, and results will be disseminated via publications in peer-reviewed journals and conference presentations in 2025. The results will advance our understanding of coagulation management in bleeding surgical patients, potentially reducing the need for allogeneic blood products and improving outcomes in surgical patients.Trial registration numberNCT05523297.
Exploring self-care choices: a qualitative study of self-medication insights among university students in Lira City, Northern Uganda
Authors: Ikwara Emmanuel Asher , Siu Godfrey , Esther Akiru , Nyadoi Ruth , Humphrey Atwijukiire 
Published: August 2024

BackgroundSelf-medication, the practice of treating health issues without professional medical guidance, is a widespread phenomenon among students globally, raising concerns about potential consequences. This study investigates perceptions and knowledge of self-medication among students from a university in Uganda.MethodsWe conducted a qualitative study, with 20 in-depth interviews and 3 focus group discussions among students. Data were processed and analysed using NVivo V.12.ResultsThis study found both positive and negative perceptions of self-medication among university students. Positive views highlighted the perception that self-medication was convenient and time-efficient method for managing health concerns as access drug shops enabled students to swiftly acquire medications, bypassing prolonged wait times. Self-medication shielded female students from potential stigma and judgement, by enabling them to discretely manage their menstrual health. By bypassing the need for clinic visits and accessing medications directly from drug shops, students could avoid the discomfort and inconvenience associated with public healthcare facilities, and allowing them to allocate time more productively for academic pursuits. However, students were concerned about potential negative consequences that encompassed drug resistance, overdose, complications, and potential fatality.ConclusionLimited access to convenient healthcare options, the concern for discrete access, particularly for potentially stigmatised conditions, coupled with the exigencies of academic life that demanded them to optimise time management, create a conducive environment for the prevalence of self-medication practices among university students. These themes demonstrate the intersection of health-seeking behaviours and contextual factors, shedding light on the pragmatic strategies adopted by students to navigate healthcare challenges, sometimes at the risk of harmful consequences. These issues also show the need for culturally and gender-sensitive healthcare approaches, regulatory oversight on medication practices and public health campaigns promoting safe medication practices among students.
Equity in home care use in Canada: a cross-sectional analysis of the Canadian longitudinal study on ageing
Authors: Lee James , Watt Jennifer A , Mayhew Alexandra , Sinn Chi-Ling , Schumacher Connie L , Costa Andrew P , Jones Aaron 
Published: August 2024

BackgroundAlthough home care is an essential service that enables older adults to age at home, there are concerns that not all populations have equitable access to home care services in Canada. The primary objective of this study is to describe formal home care use in Canada across a broad set of demographic and socioeconomic factors.MethodsWe conducted a cross-sectional analysis of formal home care use among community-dwelling adults aged 45+ using data from the Canadian longitudinal study on ageing (CLSA) at the 3-year post-baseline follow-up (2015–18). We calculated crude prevalences of formal home care use, stratified by functional status, within the following equity stratification factors: sex, gender, income, education, immigration history, rurality, social support and population group. We used logistic regression models with marginal effects to calculate prevalences of formal home care use while further adjusting for factors related to home care need such as functional impairment, chronic conditions, assistive device use and self-reported health.ResultsOf 43 115 CLSA participants included, we found that 8.0% used formal home care services in the previous 12 months. Higher levels of functional impairment were consistently associated with greater home care use. Our unadjusted analysis found significant variations in home care use by sex, gender, income, education, immigration history, rurality and social support. After adjusting for factors related to home care need, we found that individuals with lower income, recent immigration and lower education were significantly less likely to use formal home care services, while individuals with less social support were significantly more likely to use formal home care services.ConclusionsThis study highlights disparities in home care use in Canada by income, immigration, education and social support. These findings emphasise the importance of developing federal and provincial policies to address barriers and promote equitable access to home care.
Patterns of glycaemic control and associated factors among adult patients with diabetes attending medical referral clinics in two public hospitals in North-West Ethiopia: a cross-sectional study
Authors: Kassahun Hailemariam , Genetu Abere , Abuhay Taye , Tesfa Hiwot 
Published: August 2024

BackgroundPoor glycaemic control is the most challenging issue in diabetes care globally. The glycated haemoglobin (HbA1c) value is the most standard monitoring parameter for appropriate glycaemic control status.ObjectiveTo assess the patterns of glycaemic control and associated factors among patients with diabetes attending medical referral clinics in North-West Ethiopia.DesignAn institution-based cross-sectional study.SettingThis study was conducted in two public hospitals (Felege-Hiwot Comprehensive Specialized Hospital and Tibebe Ghion Specialized Hospital), Amhara National Regional State, North-West Ethiopia.ParticipantsA total of 355 adult patients with diabetes were included in the study using a systematic sampling technique. Patients were recruited from both hospitals proportionally between July and September 2021.Outcome measuresGlycaemic control was assessed using HbA1c levels. Data were collected using a checklist and structured questionnaire and analysed using a binary logistic regression model.ResultsThe overall prevalence of poor glycaemic control was 66.2% (95% CI 61.1% to 71%). Age 31–45 years (AOR=0.30, 95% CI 0.12 to 0.75), 46–60 years (AOR=0.12, 95% CI 0.04 to 0.33) and >60 years (AOR=0.09, 95% CI 0.02 to 0.31), lower educational status (AOR=3.48, 95% CI 1.01 to 12.01), type 2 diabetes (AOR=3.36, 95% CI 1.56 to 7.27), poor adherence to antidiabetic drugs (AOR=4.18, 95% CI 1.70 to 10.30), physical inactivity (AOR=4.30, 95% CI 2.11 to 8.76), longer duration of diabetes mellitus (AOR=2.06, 95% CI 1.13 to 3.75) and high body mass index (AOR=3.83, 95% CI 1.31 to 11.19) were associated with poor glycaemic control.ConclusionThe prevalence of poor glycaemic control was high. Age, lower educational status, type 2 diabetes, physical inactivity, high body mass index, longer duration of diabetes and poor adherence to antidiabetic drugs were associated with uncontrolled glycaemia.
Unveiling silent stories of women with stillbirth at Shai Osudoku District Hospital
Authors: Nkansah Ophelia , Osei Evans Appiah , Richardson Doris , Menlah Awube 
Published: August 2024

BackgroundStillbirth remains a prevalent issue worldwide, particularly affecting low-income and middle-income countries, where it brings immense sorrow and suffering to families, especially mothers. Sadly, support for women coping with this loss is inadequate, particularly in regions like Africa, where literature on women’s experiences of stillbirth is lacking.MethodsThis qualitative study employed a narrative design guided by William Worden’s Four Task Theory to explore the experiences of 15 women who had experienced stillbirth, selected through purposive sampling. Semistructured interviews were conducted face to face with participants, and thematic analysis was used to analyse the data.ResultsThe study identified three overarching themes and nine subthemes, revealing participants’ perspectives on factors contributing to stillbirth, the experiences of women dealing with this loss and their accounts of the care provided by healthcare professionals focusing on communication, response and logistical aspects.ConclusionMothers revealed a multitude of challenges following the loss, underscoring the imperative of providing them with essential support to navigate these difficulties. Future research should delve into coping strategies and interventions aimed at enhancing the coping mechanisms of these mothers.
PACMNET, V2, CoNEXT3, September 2024 Editorial
Authors: Mellia Marco , Steenkiste Peter , Qazi Ihsan Ayyub , Tyson Gareth 
Published: August 2024

The Proceedings of the ACM on Networking (PACMNET) series present the highest-quality research conducted in the areas of emerging computer networks and their applications. We encourage submissions that present new technologies, novel experimentation, creative use of networking technologies, and new insights made possible using analysis. The journal is strongly supported by the ACM Special Interest Group on Communications and Computer Networks (SIGCOMM) and involves top-level researchers in its Editorial Board.
This issue contains five articles that were originally submitted to the December'23 deadline, which received 82 submissions in total. Each submission underwent a rigorous review process involving more than 80 Editors coordinated by the two Associate Editors. In the first phase of the review process, each article received at least three reviews. After an online discussion phase, about half of the articles were rejected, and half were promoted to the second review phase. There, the Editors provided at least two additional reviews for each article. After a second discussion phase, the Editors selected seven long articles for a ''one-shot'' resubmission in June'24. The revised papers were then reviewed again by the same editors, resulting in five accepted papers.
This issue covers topics related to computer networks and their applications: two articles focus on network analytics, one article focuses on packet processing, one article focuses on network trace generation, and one article focuses on IP geolocation.
We want to thank the many individuals who contributed to this issue of PACMNET, in particular the authors, who submitted their best work to PACMNET, and the Associate Editors, who provided constructive feedback to the authors in their reviews and participated in the discussions. We would also like to thank the SIGCOMM Executive Committee Chair and the CoNEXT Steering Committee members who supported and guided us as usual, giving important suggestions and insights during the article selection process.
TCR-Engineered T Cells Directed against Ropporin-1 Constitute a Safe and Effective Treatment for Triple-Negative Breast Cancer
Authors: Kortleve Dian , Hammerl Dora , van Brakel Mandy , Wijers Rebecca , Roelofs Daphne , Kroese Kim , Timmermans Mieke M. , Liao Chen-Yi , Huang Shaozhuo , Trapman-Jansen Anita , Foekens Renée , Michaux Justine , de Beijer Monique T.A. , Buschow Sonja I. , Demmers Jeroen A.A. , Kok Marleen , Danen Erik H.J. , Bassani-Sternberg Michal , Martens John W.M. , Abbott Rachel J.M. , Debets Reno 
Published: August 2024

Abstract
Triple-negative breast cancer (TNBC) has an urgent need for new therapies. We discovered Ropporin-1 (ROPN1) as a target to treat TNBC with T cells. ROPN1 showed high and homogenous expression in 90% of primary and metastatic TNBC but not in healthy tissues. Human leukocyte antigen-A2-binding peptides were detected via immunopeptidomics and predictions and used to retrieve T-cell receptors (TCR) from naïve repertoires. Following gene introduction into T cells and stringent selection, we retrieved a highly specific TCR directed against the epitope FLYTYIAKV that did not recognize noncognate epitopes from alternative source proteins. Notably, this TCR-mediated killing of three-dimensional (3D) tumoroids in vitro and tumor cells in vivo and outperformed standard-of-care drugs. Finally, the T-cell product expressing this TCR and manufactured using a clinical protocol fulfilled standard safety and efficacy assays. Collectively, we have identified and preclinically validated ROPN1 as a target and anti-ROPN1 TCR T cells as a treatment for the vast majority of patients with TNBC.
Significance: Metastatic TNBC has a dismal prognosis. This study discovers Ropporin-1 as a target for T-cell therapy for most patients. The selected TCR is highly specific and sensitive in advanced models, and preclinical testing shows that the T-cell product expressing this TCR, manufactured according to good manufacturing practice, has favorable safety and potency.
Netrin-1 and UNC5B Cooperate with Integrins to Mediate YAP-Driven Cytostasis
Authors: Pearson Joel D. , Huang Katherine , Dela Pena Louis G. , Ducarouge Benjamin , Mehlen Patrick , Bremner Rod 
Published: August 2024

Abstract

Opposite expression and pro- or anti-cancer function of YAP and its paralog TAZ/WWTR1 stratify cancers into binary YAPon and YAPoff classes. These transcriptional coactivators are oncogenic in YAPon cancers. In contrast, YAP/TAZ are silenced epigenetically along with their integrin and extracellular matrix adhesion target genes in neural and neuroendocrine YAPoff cancers (e.g., small cell lung cancer, retinoblastoma). Forced YAP/TAZ expression induces these targets, causing cytostasis in part through Integrin-αV/β5, independent of the integrin-binding RGD ligand. Other effectors of this anticancer YAP function are unknown. Here, using clustered regularly interspaced short palindromic repeats (CRISPR) screens, we link the Netrin receptor UNC5B to YAP-induced cytostasis in YAPoff cancers. Forced YAP expression induces UNC5B through TEAD DNA-binding partners, as either TEAD1/4-loss or a YAP mutation that disrupts TEAD-binding (S94A) blocks, whereas a TEAD-activator fusion (TEAD(DBD)-VP64) promotes UNC5B induction. Ectopic YAP expression also upregulates UNC5B relatives and their netrin ligands in YAPoff cancers. Netrins are considered protumorigenic, but knockout and peptide/decoy receptor blocking assays reveal that in YAPoff cancers, UNC5B and Netrin-1 can cooperate with integrin-αV/β5 to mediate YAP-induced cytostasis. These data pinpoint an unsuspected Netrin-1/UNC5B/integrin-αV/β5 axis as a critical effector of YAP tumor suppressor activity.

Significance:
Netrins are widely perceived as procancer proteins; however, we uncover an anticancer function for Netrin-1 and its receptor UNC5B.
Health Disparities among Patients with Cancer Who Received Molecular Testing for Biomarker-Directed Therapy
Authors: Heath Elisabeth , Dyson Gregory , Ribeiro Jennifer R. , Xiu Joanne , Poorman Kelsey , Mamdani Hirva , Al-Hallak Mohammed N. , Shields Anthony F. , Elayoubi Jailan A. , Winer Ira S. , Cackowski Frank C. , Puckrein Gary A. , Lopes Gilberto de Lima , Jones Nathaniel , Hauke Ralph J. , Kareff Samuel A. , Radovich Milan , Sledge George W. , Spetzler David B. , Vidal Gregory A. , Marshall John L. 
Published: August 2024

Abstract
Health disparities present a barrier to successful oncology treatment. The potential for precision oncology to reduce health disparities has not previously been analyzed. We performed a retrospective analysis of 12,627 patients from six major cancer centers whose tumors underwent molecular testing at Caris Life Sciences between 2010 and 2020. Kaplan–Meier and Cox regression were used to describe and analyze overall survival. The molecular and demographic features of the cohort were analyzed by χ2 and ANOVA tests. Black patients composed 25% of the cohort and White patients 63%. Among this molecularly-tested cohort, there were minimal outcome differences based on race, geographic location, or poverty level. When analyzing the interaction of age, race, and sex, racial-based disparities were noted primarily for young non-White women in the study cohort but were more pronounced for men and women of all ages in the broader patient population within the Surveillance, Epidemiology, and End Results database. Mutations in five genes—APC, EGFR, STK11, TP53, and KRAS—were found to affect overall survival among our cohort, and their prevalence varied by race in specific tumor types. Real-world outcomes data in mutation-defined cohorts also provided additional context to previously reported therapeutic response trends. Our study shows that patients who undergo molecular testing display reduced racial health disparities compared with the general population, whereas persistent racial disparities are influenced by age and sex. Genomic-driven racial disparities should be examined at a tumor lineage-specific level. Increased access to molecular testing for all eligible patients may play a role in improving health equity.
Significance: This study is the largest of its kind to analyze health disparities and genomic features among a diverse multiinstitutional cohort of patients who underwent molecular testing. Continuing to increase awareness of and access to molecular testing approaches may help to reduce cancer health disparities and improve outcomes for all patients.
Prognostic Impact of a Decrease in Serum Carbohydrate Antigen 19-9 Levels After Preoperative Therapy for 4 Months or More for Borderline Resectable Pancreatic Cancer Abutting Major Arteries
Authors: Matsumoto Michinori , Tsunematsu Masashi , Abe Kyohei , Hamura Ryoga , Onda Shinji , Furukawa Kenei , Haruki Koichiro , Okamoto Tomoyoshi , Uwagawa Tadashi , Ikegami Toru 
Published: August 2024

Background: This study aimed to identify the prognostic factors after pancreatectomy for borderline resectable pancreatic cancer abutting major arteries (BR-A). Methods: We retrospectively investigated relationship between preoperative and intraoperative variables and overall survival (OS) through univariate and multivariate analyses. The cut-off points of preoperative therapy duration and response rates of serum carbohydrate antigen 19-9 (CA19-9) levels after preoperative therapy were determined through a minimum P-value approach using the log-rank test for OS. Overall survival was compared among patients stratified according to the independent prognostic factors and the presence or absence of pancreatectomy. Results: After pretreatment, 17 patients underwent pancreatectomy and four patients continued chemotherapy without surgery. Multivariate analysis in 17 resected BR-A patients demonstrated decreased serum CA19-9 levels and preoperative therapy duration of ≥4 months were the independent prognostic factors [hazard ratio (HR) 0.01; P = 0.002, HR 0.13; P = 0.02]. Patients who underwent surgery with decreased serum CA19-9 levels after preoperative therapy of ≥4 months had a significantly better prognosis than those without one or both of independent prognostic factors and those who did not undergo surgery (median survival time: not estimated, 23.3 months, 10.5 months, and 10.8 months; P = 0.02, P = 0.004, and P = 0.001, respectively). Furthermore, the prognosis did not significantly differ between the patients who underwent surgery without meeting either one or both criteria and those without surgery. Conclusions: Preoperative therapy duration of ≥4 months and decreased serum CA19-9 levels are independent prognostic factors among BR-A patients.
Comparing Quizzes and Social Annotation for Pre-Class Reading Accountability
Authors: Clinton-Lisell Virginia 
Published: August 2024

Background Pre-class reading assignments are frequently used to encourage students to complete assigned textbook readings. Quizzes and social annotation are both pre-class reading assignments, but it is uncertain which is more effective for student learning and motivation. Objective The purpose of this study was to compare quizzes and social annotation on student learning and motivation. Method Undergraduate students ( N = 58) in a child development course in a within-subjects counterbalanced design had quizzes for the textbook chapters covered in one unit exam and social annotation for a different exam. They were surveyed on their motivation at the end of the term. Results There were no reliable differences in student learning based on exam scores. Students generally perceived social annotation as more motivating but were more likely to submit quizzes. Conclusion Both quizzes and social annotation appear to have different benefits for students. There is not a clear answer on which one is more effective for student learning. Teaching Implications Given the mixed results, a combination or choice of quizzes or social annotation as pre-class reading assignments may be optimal.