bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of low-dose rivaroxaban in preventing recurrent major adverse cardiovascular events in coronary artery disease: a systematic review and meta-analysis of randomized controlled trials
Authors: Al Hennawi Hussam , Khan Muhammad Khuzzaim , Rasheed Faisal , Rathi Sushma , Ali Mirha , Ali Abraish , Asghar Zoha , Pasha Khadija , Ashraf Muhammad Talal , Klugherz Bruce 
Published: September 2024

Introduction
Despite advancements in coronary artery disease (CAD) management, major adverse cardiovascular events persist. Vitamin K antagonists and direct oral anticoagulants present bleeding risks. Low-dose rivaroxaban (2.5 mg) is approved by the European Society of Cardiology and the US Food and Drug Administration for CAD. The survival advantage and risk-benefit profile of combining low-dose rivaroxaban with aspirin for CAD patients remain uncertain. This meta-analysis aims to compare the efficacy of low-dose rivaroxaban plus aspirin versus aspirin monotherapy in CAD patients.

Methods
We systematically searched databases for randomized controlled trials exploring low-dose rivaroxaban with aspirin in CAD patients. Of the 6220 studies screened, five met the inclusion criteria. Primary outcomes included myocardial infarction, stroke, major bleeding events, and all-cause mortality. The analysis employed a fixed-effects model, calculating hazard ratios (HRs) and 95% confidence intervals (CIs).

Results
Five randomized controlled trials involving 41,351 participants were included. Rivaroxaban (2.5 mg) significantly reduced all-cause mortality (HR, 0.88; 95% CI, 0.81–0.95; P = 0.002), myocardial infarction (HR, 0.81; 95% CI, 0.70–0.94; P = 0.006), and stroke (HR, 0.61; 95% CI, 0.49–0.76; P < 0.00001) compared to aspirin alone. However, it increased major bleeding risk (HR, 1.66; 95% CI, 1.40–1.97; P < 0.01). Meta-regression revealed no dose-dependent impact on all-cause mortality.

Conclusion
Low-dose rivaroxaban demonstrates survival benefits and reduces myocardial infarction and stroke risks in CAD patients, albeit with an increased risk of major bleeding. Consideration of patient bleeding risk is crucial when adding rivaroxaban to antiplatelet therapy. Further research is warranted to compare its effectiveness and safety with dual antiplatelet therapy or P2Y12 inhibitors.
Hematopoietic cell transplantation for inborn errors of immunity: an update on approaches, outcomes and innovations
Authors: Williams Olatundun 
Published: September 2024

Purpose of reviewAllogeneic hematopoietic cell transplantation (HCT) is a curative option for many for inborn errors of immunity (IEI). This review highlights recent progress in the field of HCT for IEI.Recent findingsAlternative donor transplantation continues to expand donor options for patients with IEI. Reduced intensity and reduced toxicity conditioning approaches are being investigated and optimized. Immunomodulatory bridging therapies are yielding impressive progress in outcomes for primary immune regulatory disorders (PIRD) but require further study in prospective trials. Single-institution, multicenter and consortium studies have improved our understanding of factors that affect overall outcomes in IEI and outcomes in Wiskott–Aldrich syndrome (WAS), chronic granulomatous disease (CGD) and PIRD in particular. Data show that second HCT offers a viable chance of cure to some IEI patients. Late effects in IEI HCT survivors are being better characterized. Preclinical studies of chemo(radiation)-free HCT strategies hold promise for decreasing HCT toxicity.SummaryImprovements in our understanding of HCT donor choice, conditioning regimen, immunomodulatory bridging therapies, diagnostic and post-HCT surveillance testing and late effects continue to yield advancements in the field of HCT for IEI.
Integrated Stepped Alcohol Treatment With Contingency Management for Unhealthy Alcohol Use Among People With HIV: A Randomized Controlled Trial
Authors: Edelman E. Jennifer , Dziura James , Deng Yanhong , DePhilippis Dominick , Ferguson Tekeda , Brown Sheldon , Marconi Vincent C. , Goetz Matthew Bidwell , Rodriguez-Barradas Maria C. , Simberkoff Michael S. , Molina Patricia E. , Weintrob Amy C. , Maisto Stephen A. , Paris Manuel , Justice Amy C. , Bryant Kendall J. , Fiellin David A. 
Published: September 2024

Background:
We examined the impact of integrated stepped alcohol treatment with contingency management (ISAT + CM) on alcohol abstinence among people with HIV (PWH) and unhealthy alcohol use.

Methods:
In this multisite 24-week trial, we randomized PWH reporting untreated unhealthy alcohol use and with phosphatidylethanol (PEth) >20 ng/mL to receive ISAT+CM or treatment as usual (TAU). Intervention: Step 1: Social worker-delivered CM; Step 2: Addiction physician management plus motivational enhancement therapy. Participants were advanced to step 2 at week 12 if they lacked evidence of abstinence over the prior 21 days. TAU: Health handout, and for those who met criteria for alcohol use disorder, a referral to substance use treatment. Primary outcome: self-reported abstinence for the past 21 days at week 24.

Results:
We enrolled 120 PWH between January 5, 2018, and March 1, 2022. Mean age was 59 years, 96% were men, and 83% were Black. Eight percent were lost to follow-up. In the ISAT+CM group, 87% were advanced to Step 2. The posterior mean proportion of participants with self-reported abstinence at 24 weeks was higher among those randomized to ISAT+CM [posterior mean proportion 9% (95% credible interval [CrI]: 0%–33%)] compared with TAU [posterior mean proportion 0.3% (95% CrI: 0%–4%)] [posterior mean treatment effect 9%, (95% CrI: 0%–32%)], the posterior probability of TAU being superior to ISAT + CM was <0.0001.

Discussion:
ISAT + CM delivered in HIV clinics modestly increased self-reported 3-week abstinence among PWH. Our findings indicate a need for more effective treatments to promote abstinence and a potential role for ISAT + CM for reductions in alcohol use.

Trial registration:
Clinicaltrials.gov (NCT03089320).
Ancestry and somatic profile predict acral melanoma origin and prognosis
Authors: Basurto-Lozada Patricia , Vázquez-Cruz Martha Estefania , Molina-Aguilar Christian , Jiang Amanda , Deacon Dekker C. , Cerrato-Izaguirre Dennis , Simonin-Wilmer Irving , Arriaga-González Fernanda G. , Contreras-Ramírez Kenya L. , Dawson Eric T. , Wong-Ramirez J. Rene C. , Ramos-Galguera Johana Itzel , Álvarez-Cano Alethia , García-Ortega Dorian Y. , García-Salinas Omar Isaac , Hidalgo-Miranda Alfredo , Cisneros-Villanueva Mireya , Martínez-Said Héctor , Arends Mark J. , Ferreira Ingrid , Tullett Mark , Olvera-León Rebeca , van der Weyden Louise , del Castillo Velasco Herrera Martín , Roldán-Marín Rodrigo , Vidaurri de la Cruz Helena , Tavares-de-la-Paz Luis Alberto , Hinojosa-Ugarte Diego , Belote Rachel L. , Bishop D. Timothy , Díaz-Gay Marcos , Alexandrov Ludmil B. , Sánchez-Pérez Yesennia , In Gino K. , White Richard M. , Possik Patrícia A. , Judson-Torres Robert L. , Adams David J. , Robles-Espinoza Carla Daniela 
Published: September 2024

AbstractAcral melanoma, which is not ultraviolet (UV)-associated, is the most common type of melanoma in several low- and middle-income countries including Mexico. Latin American samples are significantly underrepresented in global cancer genomics studies, which directly affects patients in these regions as it is known that cancer risk and incidence may be influenced by ancestry and environmental exposures. To address this, here we characterise the genome and transcriptome of 128 acral melanoma tumours from 96 Mexican patients, a population notable because of its genetic admixture. Compared with other studies of melanoma, we found fewer frequent mutations in classical driver genes such asBRAF,NRASorNF1. While most patients had predominantly Amerindian genetic ancestry, those with higher European ancestry had increased frequency ofBRAFmutations and a lower number of structural variants. TheseBRAF-mutated tumours have a transcriptional profile similar to cutaneous non-volar melanocytes, suggesting that acral melanomas in these patients may arise from a distinct cell of origin compared to other tumours arising in these locations.KITmutations were found in a subset of these tumours, and transcriptional profiling defined three expression clusters; these characteristics were associated with overall survival. We highlight novel low-frequency drivers, such asSPHKAP, which correlate with a distinct genomic profile and clinical characteristics. Our study enhances knowledge of this understudied disease and underscores the importance of including samples from diverse ancestries in cancer genomics studies.
Correlates of Self-Sampling Willingness for HPV-DNA Testing among Medically Underserved Rural Kenyan Women: A Mixed Methods Study
Authors: Chepkorir Joyline , Perrin Nancy , Kivuti-Bitok Lucy , Gallo Joseph J , Gross Deborah , Anderson Jean , Reyolds Nancy R , Wyche Susan , Kibet Hillary , Kipkuri Vincent , Cherotich Anastacia , Han Hae-Ra 
Published: September 2024

AbstractIntroductionCervical cancer is the leading cause of cancer-related deaths among Sub-Saharan African women, particularly in rural areas where screening rates are lower due to limited access to highly sensitive tests. This study aimed to investigate factors that might influence rural Kenyan women’s willingness to self-collect samples for HPV-DNA testing.MethodsThis study utilized data from a mixed-methods study in Bomet and Kericho Counties, including survey responses from 174 women and semi-structured interviews with a subset of 21 participants. Logistic regression was used to analyze quantitative data and theoretical thematic analysis for qualitative data.ResultsThe surveyed women had a mean age of 45.2 years, were mainly uninsured (76%) and from low-income households (88.4%). Most participants had heard of cervical cancer (83.2%), yet only 6.4% had ever been screened. However, 76.9% expressed willingness to self-collect samples for HPV-DNA testing. Factors significantly associated with increased self-sampling willingness were cervical cancer awareness (OR=3.49, 95% CI=1.50-8.11), having health workers (OR=1.88, CI=1.23-2.86) and the news media (radio and television) (OR=2.63, CI=1.27-5.48) as primary sources of health information, and ever hearing about cervical cancer from the news media (OR=2.43, CI=1.07-5.51). Conversely, high cervical cancer stigma (OR=0.71, CI=0.57-0.88) and longer travel time of 30 to 120 minutes to the nearest health facility (OR=0.44, CI=0.20-0.93) were associated with decreased willingness. Interview data corroborated these findings.ConclusionsCervical cancer screening uptake is notably low among rural Kenyan women in Bomet and Kericho Counties. Sample self-collection for HPV-DNA testing appears widely acceptable. A comprehensive approach involving educational outreach, health worker recommendation, and mass media campaigns could enhance cervical cancer screening via self- sampling, potentially reducing the burden of cervical cancer. Future research should employ implementation science methodologies to explore cervical cancer screening uptake via self- sampling, to inform population-based implementation strategies in Kenya.
A novel alpha-synuclein G14R missense variant is associated with atypical neuropathological features
Authors: Brücke Christof , Al-Azzani Mohammed , Ramalingam Nagendran , Ramón Maria , Sousa Rita L. , Buratti Fiamma , Zech Michael , Sicking Kevin , Amaral Leslie , Gelpi Ellen , Chandran Aswathy , Agarwal Aishwarya , Chaves Susana R. , Fernández Claudio O. , Dettmer Ulf , Lautenschläger Janin , Zweckstetter Markus , Busnadiego Ruben Fernandez , Zimprich Alexander , Outeiro Tiago Fleming 
Published: September 2024

AbstractBackgroundParkinson’s disease (PD) affects millions of people worldwide, but only 5–10% of patients suffer from a monogenic form of the disease with Mendelian inheritance.SNCA,the gene encoding for the protein alpha-synuclein (aSyn), was the first to be associated with familial forms of PD and, since then, several missense variants and multiplications of theSNCAgene have been established as rare causes of autosomal dominant forms of PD.Aim and methodsA patient carrying aSyn missense mutation and his family members were studied. We present the clinical features, genetic testing - whole exome sequencing (WES), and neuropathological findings. The functional consequences of this aSyn variant were extensively investigated using biochemical, biophysical, and cellular assays.ResultsThe patient exhibited a complex neurodegenerative disease that included generalized myocloni, bradykinesia, dystonia of the left arm and apraxia. WES identified a novel heterozygousSNCAvariant (cDNA 40G>A; protein G14R). Neuropathological examination showed extensive atypical aSyn pathology with frontotemporal lobar degeneration (FTLD) and nigral degeneration pattern with abundant ring-like neuronal inclusions, and few oligodendroglial inclusions. Sanger sequencing confirmed theSNCAvariant in the healthy, elderly parent of the patient patient suggesting incomplete penetrance. NMR studies suggest that the G14R mutation induces a local structural alteration in aSyn, and lower thioflavin T binding in in vitro fibrillization assays. Interestingly, the G14R aSyn fibers display different fibrillar morphologies as revealed by cryo-electron microscopy. Cellular studies of the G14R variant revealed increased inclusion formation, enhanced membrane association, and impaired dynamic reversibility of serine-129 phosphorylation.SummaryThe atypical neuropathological features observed, which are reminiscent of those observed for the G51D aSyn variant, suggest a causal role of theSNCAvariant with a distinct clinical and pathological phenotype, which is further supported by the properties of the mutant aSyn, compatible with the strain hypothesis of proteinopathies.
Exploring a roadmap to achieving tobacco endgame in sub-Saharan Africa: A qualitative study among stakeholders from 12 countries
Authors: Egbe Catherine O. , Ngobese Senamile P. , Khan Arshima , Gwambe Siphesihle , Ngcobo Zinhle P. , Bialous Stella A. 
Published: September 2024

ABSTRACTIntroductionTobacco endgame seeks to bring an end to tobacco use or drastically reduce prevalence to <5%. Discussions about tobacco endgame and the possible strategies to achieve this goal in Sub-Saharan African (SSA) are sparse. This study aimed to explore SSA tobacco control stakeholders’ perspectives about tobacco endgame and ascertain what strategies they perceive to be suitable for the region to achieve this.MethodsThis was a qualitative study involving a purposive sample of 29 stakeholders interviewed via online platforms guided by a semi-structured interview schedule. Stakeholders were from academia, civil society, and government departments in 12 SSA countries. Interviews were conducted in English or French, transcribed verbatim (those in French were translated to English) and thematically analyzed with the aid of NVIVO v12.ResultsThere is support for the adoption of tobacco endgame in SSA by tobacco control stakeholders in in the region due to the impact tobacco has on health, the environment and economy. Proposed endgame approaches for SSA were recommended to be Afrocentric which must be sensitive to cultural and regional dynamics. Stakeholders believed that the success of endgame strategies depends on political will, multi-sectoral collaboration, availability of resources, buy-in from the public and tobacco industry monitoring. Suggested endgame strategies were categorized into 5 themes: Product-focused (less addictive tobacco and regulation of novel products); User-focused (smoke-free generation, cessations supports and use of sports); Market/supply-focused (licensing of sellers, increase in taxes, control of illicit trade and alternative income for farmers); Institutional structure-focused (tobacco industry monitoring and regulation) and legislation implementation-focused (effective implementation of international treaties aimed at lowering tobacco use prevalence).ConclusionThere is support for a tobacco endgame in SSA. Collaboration from various departments/ministries, and support from government and the public would be needed to make tobacco endgame a reality in SSA.Key HighlightsDiscussion on how to end tobacco use (endgame) in Sub-Saharan African (SSA) is sparse.Tobacco control stakeholders in SSA are supportive of tobacco endgame for the region.Afrocentric endgame strategies sensitive to culture and countries’ peculiarities are needed.User, product and supply focused, as well as institutional and legislation focused strategies have been proposed.Proposed endgame strategies must include alternative income for farmers and cessation support.Support from SSA governments and the public, and tobacco industry monitoring are needed for successful implementation of tobacco endgame in SSA.
Cascaded Multimodal Deep Learning in the Differential Diagnosis, Progression Prediction, and Staging of Alzheimer’s and Frontotemporal Dementia
Authors: Guarnier Gianmarco , Reinelt Janis , Molloy Eóin N. , Mihai Paul Glad , Einaliyan Pegah , Valk Sofie , Modestino Augusta , Ugolini Matteo , Mueller Karsten , Wu Qiong , Babayan Anahit , Castellaro Marco , Villringer Arno , Scherf Nico , Thierbach Konstantin , Schroeter Matthias L. ,   the Alzheimer’s Disease Neuroimaging Initiative ageing the Australian Imaging Biomarkers and Lifestyle flagship study of Initiative and the Frontotemporal Lobar Degeneration Neuroimaging
Published: September 2024

AbstractDementia syndromes are complex sequelae whose multifaceted nature poses significant challenges in the diagnosis, prognosis, and treatment of patients. Despite the availability of large open-source data fueling a wealth of promising research, effective translation of preclinical findings to clinical practice remains difficult. This barrier is largely due to the complexity of unstructured and disparate preclinical and clinical data, which traditional analytical methods struggle to handle. Novel analytical techniques involving Deep Learning (DL), however, are gaining significant traction in this regard. Here, we have investigated the potential of a cascaded multimodal DL-based system (TelDem), assessing the ability to integrate and analyze a large, heterogeneous dataset (n=7159 patients), applied to three clinically relevant use cases. Using a Cascaded Multi-Modal Mixing Transformer (CMT), we assessed TelDem’s validity and (using a Cross Modal Fusion Norm - CMFN) model explainability in (i) differential diagnosis between healthy individuals, AD, and three sub-types of frontotemporal lobar degeneration (ii) disease staging from healthy cognition to mild cognitive impairment (MCI) and AD, and (iii) predicting progression from MCI to AD. Our findings show that the CMT enhances diagnostic and prognostic accuracy when incorporating multimodal data compared to unimodal modeling and that cerebrospinal fluid (CSF) biomarkers play a key role in accurate model decision making. These results reinforce the power of DL technology in tapping deeper into already existing data, thereby accelerating preclinical dementia research by utilizing clinically relevant information to disentangle complex dementia pathophysiology.
Early menarche and childbirth accelerate aging-related outcomes and age-related diseases: Evidence for antagonistic pleiotropy in humans
Authors: Xiang Yifan , Tanwar Vineeta , Singh Parminder , La Follette Lizellen , Narayan Vikram , Kapahi Pankaj 
Published: September 2024

AbstractAging can be understood as a consequence of the declining force of natural selection with age. Consistent with this, the antagonistic pleiotropy theory of aging proposes that aging arises from trade-offs that favor early growth and reproduction. However, evidence supporting antagonistic pleiotropy in humans remains limited. Using Mendelian Randomization (MR), we demonstrated that later ages of menarche or first childbirth were genetically associated with longer parental lifespan, decreased frailty index, slower epigenetic aging, later menopause, and reduced facial aging. Moreover, later menarche or first childbirth were also genetically associated with a lower risk of several age-related diseases, including late-onset Alzheimer’s disease (LOAD), type 2 diabetes, heart disease, essential hypertension, and chronic obstructive pulmonary disease (COPD). We validated the associations between the age of menarche, childbirth, and the number of childbirths with several age-related outcomes in the UK Biobank by conducting regression analysis of nearly 200,000 subjects. Our results demonstrated that menarche before the age 11 and childbirth before 21 significantly accelerated the risk of several diseases, and almost doubled the risk for diabetes, heart failure, and quadrupled the risk of obesity, supporting the antagonistic pleiotropy theory. We identified 126 significant single nucleotide polymorphisms (SNPs) that influenced age-related outcomes, some of which were involved in known longevity pathways, including IGF1, growth hormone, AMPK, and mTOR signaling. Our study also identified higher BMI as a mediating factor in causing the increased risk of certain diseases, such as type 2 diabetes and heart failure, in women with early menarche or early pregnancy, emphasizing the importance of the thrifty gene hypothesis in explaining in part the mechanisms behind antagonistic pleiotropy. Our study highlights the complex relationship between genetic legacies and modern diseases, emphasizing the need for gender-sensitive healthcare strategies that consider the unique connections between female reproductive health and aging.
Informing an Intervention to Improve Access to Community Pharmacist-Provided Injectable Naltrexone for Formerly Incarcerated Individuals in Wisconsin
Authors: Chladek Jason S. , Chui Michelle A. 
Published: September 2024

AbstractIn Wisconsin, opioid use disorder (OUD) is highly prevalent among individuals impacted by the criminal justice system. Medications for opioid use disorder (MOUD), including injectable naltrexone, are crucial for treating OUD and especially important for individuals transitioning out of correctional facilities and back into the community. Unfortunately, few formerly incarcerated individuals are able to access MOUD upon community reentry, remaining at high risk of overdose and rearrest. Community pharmacists are a promising resource for providing injectable naltrexone to formerly incarcerated individuals using this treatment option, but are underutilized during reentry planning and by formerly incarcerated individuals upon release. This is due, in large part, to several barriers that exist across the socioecological scale. Accordingly, this study utilized a participatory design process to inform an intervention that address these barriers and improves access to community pharmacist-provided injectable naltrexone for formerly incarcerated individuals upon community reentry. Three iterative focus groups were conducted with five community pharmacists who have experience providing injectable naltrexone and treating formerly incarcerated patients. The goals of each focus group were to: 1) discuss perceptions of existing barriers and prioritize barriers to be addressed, 2) discuss and rank potential interventions to address the prioritized barriers, and 3) discuss components and anticipated challenges related to the prioritized intervention. Focus groups were analyzed via deductive content analysis using a priori categories. Based on discussions of perceived impact and feasibility, the participants prioritized two barriers to be addressed: lack of awareness of community pharmacist-provided injectable naltrexone services and lack of interagency collaboration among primary care clinics, community pharmacies, and correctional facilities. The final intervention included pharmacist-led educational meetings with correctional providers and reentry staff. Several intervention components and anticipated challenges were also identified. Next steps include developing, implementing, and evaluating the efficacy of the intervention on improving access to community pharmacist-provided injectable naltrexone for formerly incarcerated individuals.