bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brief Report: Unmet Need for Solid Organ Transplantation Among People With HIV and End-Stage Kidney or Liver Disease: A Brief Report From the HIV Outpatient Study, 2009–2023
Authors: Mayer Cynthia , Agbobli-Nuwoaty Selom Enyo , Li Jun , Carlson Kimberly , Palella Frank J. , Durham Marcus D. , Buchacz Kate ,   for the HIV Outpatient Study (HOPS)
Published: August 2024

Background:
Persons with HIV (PWH) with end-stage kidney disease (ESKD) who are eligible for kidney transplantation have post-transplantation outcomes similar to those without HIV infection. However, barriers to referral for care, evaluation, and receipt of transplants remain for PWH. We sought to identify PWH with ESKD or end-stage liver disease (ESLD) who would be candidates for organ transplant and to review their clinical outcomes.

Methods:
We analyzed data from participants in the HIV Outpatient Study (HOPS) between January 1, 2009, and June 30, 2023, with a diagnosis of ESKD or ESLD. We identified a subset of PWH who would otherwise meet the general criteria for kidney or liver transplantation. Targeted clinical outcomes included dialysis, transplantation, and death.

Results:
Among 5215 PWH in the HOPS, 258 with ESKD and 23 with ESLD would otherwise meet the criteria for transplant. However, only 9 kidney and 2 liver transplants were performed.

Conclusions:
Low transplantation rates among eligible PWH suggest that timely referral for care and evaluation for kidney and liver transplantation often does not occur. Expanding access for PWH with ESKD to both deceased and living donor kidney allografts is needed. Kidney and liver transplant centers also need to seek ways to broaden access for eligible PWH with ESKD or ESLD.
Evaluation of Four Interventions Using Behavioral Economics Insights to Increase Demand for Voluntary Medical Male Circumcision in South Africa Through the MoyaApp: A Quasi-Experimental Study
Authors: Mistri Preethi , Tomescu Silviu , Bokolo Simamkele , De Nooy Alexandra , Pisa Pedro T. , Grove Skye , Schmucker Laura , Chetty-Makkan Candice , Long Lawrence , Buttenheim Alison , Maughan-Brown Brendan 
Published: August 2024

Background:
While voluntary medical male circumcision (VMMC) reduces the risk of HIV transmission by 60%, circumcision coverage falls short of the UNAIDS 90% VMMC target. We investigated whether behaviorally informed message framing increased demand for VMMC.

Setting:
Adult users of the MoyaApp, a data-free application in South Africa, who viewed a form designed to generate interest in VMMC from August 2022 to November 2022.

Methods:
A quasi-experimental study was conducted to evaluate 4 MoyaApp VMMC intervention forms against the standard-of-care (SOC) form. All forms enabled users to provide contact details for follow-up engagement by a call center. The primary outcome was the proportion of forms submitted. Secondary outcomes included successful contact with the user, VMMC bookings/referrals, and confirmed circumcision. Multivariable ordinary least-squares regression was used for the analysis.

Results:
Of 118,337 MoyaApp VMMC form viewers, 6% submitted a form. foot-in-the-door form viewers were more likely (+1.3 percentage points, P < 0.01) to submit a form compared with the SOC group (6.3%). Active Choice (−1.1 percentage points, P < 0.01) and Reserved for You (−0.05 percentage points, P < 0.05) form viewers were less likely to submit a form compared with SOC form. Users submitting the foot-in-the-door form were less likely to be booked/referred compared with those using the SOC form (−5 percentage points, P < 0.05). There were no differences between the intervention and SOC forms for successful contact and circumcisions.

Conclusions:
Message framing using behavioral insights was able to nudge men to engage with VMMC services. However, more work is needed to understand how to convert initial interest into bookings and circumcisions.
R21 malaria vaccine is protective against intradermal but not intravenousPlasmodium falciparumsporozoites in a randomized controlled human malaria infection study in Kenyan adults
Authors: Kapulu Melissa C , Orenge Francesca , Kimani Domtila , Kibwana Elizabeth , Kibet Hillary , Mutahi Mary , Datoo Mehreen S , Bellamy Duncan , Musembi Janet , Ngoto Omar , Rashid Hamisi , Akinyi Stellamaris , Mwatasa Mwaganyuma H , Nyamako Lydia , Keter Kelvias , Gatheru Rose , Mutiso Agnes , Musyoki Jennifer , Mwacharo Jedidah , Abebe Yonas , James Eric J , Billingsley Peter F , Ngetsa Caroline , Mosobo Moses , Makale Johnstone , Tawa Brian , Wamae Kevin , Ochola-Oyier Lynette I , Wambua Juliana , Lawrie Alison , Ramos-Lopez Fernando , Roberts Rachel , Richie Thomas L , Sim B. Kim Lee , Hoffman Stephen L , Ewer Katie J , Hill Adrian V S , Hamaluba Mainga , Bejon Philip 
Published: August 2024

AbstractFalciparum malaria is a substantial public health problem. Vaccines and monoclonal antibodies targeting thePlasmodium falciparum(Pf) circumsporozoite protein (CSP) are promising control strategies. The protective mechanisms of anti-PfCSP antibodies are incompletely understood, and levels of anti-PfCSP antibodies are inconsistently predictive of protection. We undertook controlled human malaria infections in volunteers vaccinated with the PfCSP-based vaccine R21/Matrix-M, using either intradermal injection (ID) or direct venous inoculation (DVI) ofP. falciparumsporozoites (PfSPZ Challenge). R21/Matrix-M was highly protective against intradermal inoculation of PfSPZ Challenge (i.e. 100%, 12 out of 12) but not protective against PfSPZ Challenge by DVI (i.e. 0%, 0 out of 5). These findings imply that the variable delivery of Pf sporozoites into capillaries rather than the subdermal layers by infectious mosquito bites can account for the inconsistent protection provided by anti-PfCSP antibodies.
A Draft Pacific Ancestry Pangenome Reference
Authors: Littlefield Connor , Lazaro-Guevara Jose M. , Stucki Devorah , Lansford Michael , Pezzolesi Melissa H. , Taylor Emma J. , Wolfgramm Etoni-Ma’asi C. , Taloa Jacob , Lao Kime , Dumaguit C. Dave C. , Ridge Perry G. , Tavana Justina P. , Holland William L. , Raphael Kalani L. , Pezzolesi Marcus G. 
Published: August 2024

AbstractIndividuals of Pacific ancestry suffer some of the highest rates of health disparities yet remain vastly underrepresented in genomic research, including currently available linear and pangenome references. To begin addressing this, we developed the first Pacific ancestry pangenome reference using 23 individuals with diverse Pacific ancestry. We assembled 46 haploid genomes from these 23 individuals, resulting in highly accurate and contiguous genome assemblies with an average quality value of 55.0 and an average N50 of 40.7 Mb, marking the firstde novoassembly of highly accurate Pacific ancestry genomes. We combined these assemblies to create a pangenome reference, which added 30.6 Mb of novel sequence missing from the Human Pangenome Reference Consortium (HPRC) reference. Mapping short reads to this pangenome reduced variant call errors and yielded more true-positive variants compared to the HPRC and T2T-CHM13 references. This Pacific ancestry pangenome reference serves as a resource to enhance genetic analyses for this underserved population.
Structure and function of the human apoptotic scramblase Xkr4
Authors: Chakraborty Sayan , Feng Zhang , Lee Sangyun , Alvarenga Omar E. , Panda Aniruddha , Bruni Renato , Khelashvili George , Gupta Kallol , Accardi Alessio 
Published: August 2024

AbstractPhosphatidylserine externalization on the surface of dying cells is a key signal for their recognition and clearance by macrophages and is mediated by members of the X-Kell related (Xkr) protein family. Defective Xkr-mediated scrambling impairs clearance, leading to inflammation. It was proposed that activation of the Xkr4 apoptotic scramblase requires caspase cleavage, followed by dimerization and ligand binding. Here, using a combination of biochemical approaches we show that purified monomeric, full-length human Xkr4 (hXkr4) scrambles lipids. CryoEM imaging shows that hXkr4 adopts a novel conformation, where three conserved acidic residues create an electronegative surface embedded in the membrane. Molecular dynamics simulations show this conformation induces membrane thinning, which could promote scrambling. Thinning is ablated or reduced in conditions where scrambling is abolished or reduced. Our work provides insights into the molecular mechanisms of hXkr4 scrambling and suggests the ability to thin membranes might be a general property of active scramblases.
Revealing unseen dynamical regimes of ecosystems from population time-series data
Authors: Medeiros Lucas P. , Sorenson Darian K. , Johnson Bethany J. , Palkovacs Eric P. , Munch Stephan B. 
Published: August 2024

AbstractMany ecosystems can exist in alternative dynamical regimes for which small changes in an environmental driver can cause sudden jumps between regimes. However, predicting the dynamics of regimes that occur under unobserved levels of the environmental driver has remained an unsolved challenge in ecology with important implications for conservation and management. Here we show that integrating population time-series data and information on the putative driver into an empirical dynamic model allows us to predict new dynamical regimes without the need to specify a population dynamics model. As a proof of concept, we demonstrate that we can accurately predict fixed-point, cyclic, or chaotic dynamics under unseen driver levels for a range of simulated models. For a model with an abrupt population collapse, we show that our approach can anticipate the regime that follows the tipping point. We then apply our approach to data from an experimental microbial ecosystem and from a lake planktonic ecosystem. We find that we can reconstruct transitions away from chaos in the experimental ecosystem and anticipate the dynamics of the oligotrophic regime in the lake ecosystem. These results lay the groundwork for making rational decisions about preventing, or preparing for, regime shifts in natural ecosystems.
Renal cancer cells acquire immune surface protein through trogocytosis and horizontal gene transfer
Authors: Marcarian Haley Q. , Sivakoses Anutr , Arias Anika M. , Ihedioha Olivia C. , Lee Benjamin R. , Bishop Maria C. , Bothwell Alfred L.M. 
Published: August 2024

ABSTRACTTrogocytosis is an underappreciated phenomenon that shapes the immune microenvironment surrounding many types of solid tumors. The consequences of membrane-bound proteins being deposited from a donor immune cell to a recipient cancer cell via trogocytosis are still unclear. Here, we report that human clear cell renal carcinoma tumors stably express the lymphoid markers CD45, CD56, CD14, and CD16. Flow cytometry performed on fresh kidney tumors revealed consistent CD45 expression on tumor cells, as well as varying levels of the other markers mentioned previously. These results were consistent with our immunofluorescent analysis, which also revealed colocalization of lymphoid markers with carbonic anhydrase 9 (CAIX), a standard kidney tumor marker. RNA analysis showed a significant upregulation of genes typically associated with immune cells in tumor cells following trogocytosis. Finally, we show evidence of chromosomal DNA being transferred from immune cells to tumor cells during trogocytosis. This horizontal gene transfer has transcriptional consequences in the recipient tumor cell, resulting in a fusion phenotype that expressed both immune and cancer specific proteins. This work demonstrates a novel mechanism by which tumor cell protein expression is altered through the acquisition of surface membrane fragments and genomic DNA from infiltrating lymphocytes. These results alter the way in which we understand tumor-immune cell interactions and may reveal new insights into the mechanisms by which tumors develop. Additionally, further studies into trogocytosis will help push the field towards the next generation of immunotherapies and biomarkers for treating renal cell carcinoma and other types of cancers.SIGNIFICANCE STATEMENTWe have identified trogocytosis as a mechanism by which human clear cell renal carcinoma tumors acquire lymphocyte surface protein expression from tumor infiltrating immune cells. In addition to the transfer of membrane fragments, we have provided evidence to show that genomic DNA is transferred from a normal immune cell to a tumor cell during trogocytosis. This process alters the transcriptome of cancer cells such that they express significantly more mRNA for immune proteins such as the lymphocyte marker CD45 compared to tumor cells that have not undergone trogocytosis. This study provides an in-depth analysis of the interactions between cancer cells and tumor infiltrating lymphocytes, and how these interactions alter the development of human tumors.
Generating Multi-state Conformations of P-type ATPases with a Conditional Diffusion Model
Authors: Xu Jingtian , Wang Yong 
Published: August 2024

AbstractUnderstanding and predicting the diverse conformational states of membrane proteins is essential for elucidating their biological functions. Despite advancements in computational methods, accurately capturing these complex structural changes remains a significant challenge. Here we introduce a computational approach to generate diverse and biologically relevant conformations of membrane proteins using a conditional diffusion model. Our approach integrates forward and backward diffusion processes, incorporating state classifiers and additional conditioners to control the generation gradient of conformational states. We specifically targeted the P-type ATPases, a critical family of membrane transporters, and constructed a comprehensive dataset through a combination of experimental structures and molecular dynamics simulations. Our model, incorporating a graph neural network with specialized membrane constraints, demonstrates exceptional accuracy in generating a wide range of P-type ATPase conformations associated with different functional states. This approach represents a meaningful step forward in the computational generation of membrane protein conformations using AI and holds promise for studying the dynamics of other membrane proteins.TOC Graphic
Evaluation of anti-CENP reactivity in samples with centromere HEp-2 pattern and correlation with Systemic Sclerosis clinical features
Authors: Keppeke Gerson D. , Landoni Diana , Kayser Cristiane , Matos Pedro , Diogenes Larissa , Keppeke Jessica , Rodrigues Silvia Helena , Andrade Luis Eduardo C. 
Published: August 2024

AbstractBackground/ObjectivesAnti-centromere antibodies are associated with limited cutaneous Systemic Sclerosis (lcSSc) and in general, with a more favorable prognosis for SSc. Centromere pattern (AC-3) observed in the immunofluorescence assay in HEp-2 cells (HEp-2-IFA) suggests the presence of antibodies against CENP antigens, mainly CENP-B/A. In this study, we evaluated the frequency of reactivity to CENP-B and CENP-A in samples with an AC-3 pattern in the HEp-2-IFA. We also correlated the demographic and clinical characteristics of SSc patients according to the presence of the AC-3 pattern.MethodsSamples from 39 SSc patients with AC-3 pattern were included and evaluated for CENP-B/A reactivity by line-blot and indirect ELISA. As controls, 48 lcSSc without the AC-3 pattern (Non-AC-3 group) were included. Clinical characteristics were recovered for 69 patients, 21 with AC-3 and all those in the Non-AC-3 group.ResultsOut of 39 samples with AC-3, 33 (84.6%) were reactive against CENP-B and 32 (82.1%) were reactive against CENP-A using the line-blot assay. Using anti-CENP-B ELISA, 36 (92.3%) of the samples with AC-3 were positive for anti-CENP-B. There was 79.5% concordance for CENP-B reactivity between ELISA and line-blot. Using the immunoblot assay, 27 (69.2%) of the samples with AC-3 were reactive against CENP-B and CENP-A, and one sample was positive only for CENP-A. Altogether, 38 samples (97.4%) were reactive against CENP-B by at least one method and all 39 samples (100%) were positive for either CENP-B or CENP-A in at least one of the tests. Regarding the clinical features, interstitial lung disease was less frequent in patients with AC-3 pattern compared to Non-AC-3 (10%versus54.2%; p=0.001). Other organ involvement parameters had similar frequencies between the groups.ConclusionsIn conclusion, the HEp-2-IFA method was 100% sensitive in detecting antibodies to CENP-A and CENP-B. Anti-CENP-B is the predominant autoantibody in samples yielding the AC-3 pattern, but exclusive anti-CENP-A reactivity was observed less frequently. Among lcSSc patients, anti-centromere reactivity was associated with less frequent lung involvement.
Safety, Feasibility, and Utility of Digital Mobile Six-Minute Walk Testing in Pulmonary Arterial Hypertension: The DynAMITE Study
Authors: Schütz Narayan , Glinskii Vlad , Anderson Ryan , Del Rosario Patricia , Hedlin Haley , Lee Justin , Hess John , Van Wormer Steve , Lopez Alejandra , Hershman Steven G , De Jesus Perez Vinicio , Zamanian Roham T. 
Published: August 2024

ABSTRACTRationalePulmonary arterial hypertension (PAH) is a life-threatening progressive cardiopulmonary disease associated with high morbidity and mortality. Changes in the six-minute walk test (6MWT) provide prognostic information and help guide treatment decisions for PAH. However, since 6MWT requires in-clinic visits, clinical interventions to address disease progression may be delayed. Wearable technologies could reduce this delay by allowing the performance of 6MWT in the community and delivering data to clinicians remotely.ObjectivesTo perform a pilot study to determine the safety and feasibility of performing 6MWT in PAH outpatients using a wearable app-based tool.MethodsPAH patients recruited at Stanford University were provided an Apple Watch with an app to perform daily, self-administered 6MWT over 12 weeks. Bland-Altman plots and correlations were used to assess the agreement and reliability of in-clinic vs. app-based 6MWT data at the beginning and end of the 12-week trial.Measurements and Main ResultsFrom 55 PAH participants, we collected 3,139 app-recorded walks during 979.7 patient-weeks of exposure. On average, participants performed 3±2.3 weekly walks. No serious adverse events were reported. App-derived walk distance was highly correlated (r≥ 0.9) to the baseline in-clinic 6MWD and showed excellent reliability (ICC=0.9). Correlation and agreement were significantly lower at the 12-week follow-up visit. App-derived metrics beyond 6MWD showed promising associations with disease status.ConclusionsApp-based outpatient 6MWT is feasible, safe, reasonably accurate, likely clinically relevant, and reliable in PAH patients but long-term measurement stability may be a concern. App-derived digital measures beyond distance show promise for future applications.
Medical termination of pregnancy from day 85 to day 153 of gestation: A randomized comparison between administration of the initial dose of misoprostol at home or in the clinic
Authors: Gemzell Danielsson Kristina , Rydelius Johanna 
Published: August 2024

Study ProtocolObjectivesThe objective of this study is to compare two groups of women requiring termination of pregnancy from the gestational age of 85 days. All women will receive Mifepristone during their first visit to the out-patient ward. One group of women will receive Misoprostol to administer the first dose (vaginally) at home and 2 hours later they will be admitted to the in-patient ward. They will be informed to present earlier if they start bleeding or experience pain corresponding to more than normal menstrual cramping.The other group will receive the first dose of Misoprostol (vaginally) when admitted in the in-patient ward (usually in the morning) according to current practice.Primary objectiveTo investigate the proportion of women who are successfully treated as day-care patients (day-care being defined as 9 hours from time of admission).DesignThe study will be a randomized, controlled, multi-centred open label trial with women recruited from four hospitals in Sweden.
Factors associated with breast lesions among women attending select teaching and referral health facilities in Kenya: a cross-sectional study
Authors: Rioki Josephine Nyabeta , Mweu Marshal , Rogena Emily , Songok Elijah M. , Mwangi Joseph , Muchiri Lucy 
Published: August 2024

AbstractBackgroundDespite extensive research on the risk factors for breast cancer, little is known about the factors contributing to other breast lesions, of which some may indicate an increased risk for this disease. The objective of this study was to identify the risk factors for breast lesions among women with breast lumps seeking care at select teaching and referral hospitals in Kenya between December 2016 to December 2019.MethodsAn analytical cross-sectional study design was used to investigate the risk factors for breast lesions among 651 women with breast lumps. Data was collected using a semi-structured questionnaire. A multivariable logistic regression model was used to evaluate the impact of the predictors on the breast lesions. Ethical approval was granted by Kenyatta National Hospital (KNH) and the University of Nairobi Ethics and Research Committee (UoN-ERC) under study number P334/04/2016.ResultsThe median age of participants was 30 years (range 16-87), with the majority having secondary education and belonging to the Kikuyu ethnic group. Parity, exercise, and contraceptive use were significant predictors of breast lesions identified. Nulliparous women had significantly lower odds of developing malignant (aOR: 0.11; 95% CI: 0.05-0.26), and suspicious (aOR: 0.23; 95% CI: 0.07-0.71) lesions. Regular exercise was associated with lower odds of both malignant and suspicious lesions. Conversely, contraceptive use increased the odds of developing atypical (aOR 0.92; 95% CI: 0.28-2.98) lesions, suspicious (aOR 0.33; 95% CI: 0.14-0.78), and malignant lesions (aOR of 0.31; 95% CI: 0.18-0.55).ConclusionExercise, parity, and hormonal contraception were independently found to be significant predictors of breast lesions. These findings underscore the necessity for personalized risk reduction strategies and emphasize the importance of understanding the risk factors for both benign and malignant breast disease to inform public health policies.