bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bimodal distributions of anti-Trypanosoma cruziantibody levels in blood donors are associated with parasite detection and antibody waning in peripheral blood
Authors: Remesar Mirta C. , Sabino Ester C. , Buss Lewis F. , Merlo Claudio D. , López Mónica G. , Humeres Sebastián L. , Héctor Pavón A. , Clara Di Germanio C. , Coco Sonia Bakkour , Oliveira-da Silva Léa C. , Filho Marcelo Martins Pinto , Ribeiro Antonio Luiz P. , Busch Michael P. , del Pozo Ana E. 
Published: November 2024

AbstractBackgroundIn our previous study of blood donors in the Argentinian Chaco Province, we documented bimodal distributions of anti-Trypanosoma cruziantibody (Ab) levels, suggesting potential self-cure in donors with low-reactive samples. This study aimed to correlate “high” and “low” Ab level groups, defined by a mathematical model, with parasitemia and electrocardiogram findings. Ab decline over time was also assessed.Methodology / Principal FindingsWe invitedT. cruziAb reactive blood donors to enroll in the study from October 2018 to November 2019 with a follow up visit two years later. Blood samples were tested forT cruziAb by: Chagatest ELISA Lisado and Chagatest ELISA Recombinante v.4.0 (Wiener Lab, Argentina); VITROS Immunodiagnostic Products Anti-T.cruzi (Chagas) (Ortho-Clinical Diagnostics Inc., UK), and Architect Chagas (Abbott Laboratories, Germany). Target capture PCR was performed on lysed whole blood samples from enrollment visits and electrocardiograms on second visits.Four hundred fifty donors were recruited, but 68 were excluded due to negative results on all study Ab assays. Ab level distributions were bimodal and classified as “high” or “low” at a calculated threshold for each of four assays. There were 160 donors with low and 179 with high Ab results on all assays. The remainder 43 were discordant reactive. Ninety-seven percentage of the PCR positive donors were among the concordant high Ab group. During the 2-4 year follow-up interval, relative Ab declines by three assays were significantly greater among those classified as low Ab and with negative PCR results.Conclusions / SignificanceAb reactivity is associated with PCR-detectable parasitemia. Greater Ab declines were detected among donors with low and/or discordant Ab reactivity and negative PCR results, suggesting spontaneous parasite clearance in these donors.
Cross-dataset pan-cancer detection: Correlating cell-free DNA fragment coverage with open chromatin sites across cell types
Authors: Olsen Ludvig Renbo , Odinokov Denis , Holsting Jakob Qvortrup , Kondrup Karoline , Iisager Laura , Rusan Maria , Buus Simon , Laursen Britt Elmedal , Borre Michael , Jochumsen Mads Ryø , Bouchelouche Kirsten , Frydendahl Amanda , Rasmussen Mads Heilskov , Henriksen Tenna Vesterman , Nesic Marijana , Demuth Christina , Lindskrog Sia Viborg , Nordentoft Iver , Lamy Philippe , Therkildsen Christina , Dyrskjøt Lars , Sørensen Karina Dalsgaard , Andersen Claus Lindbjerg , Skanderup Anders Jakobsen , Besenbacher Søren 
Published: November 2024

AbstractThe fragmentation patterns of whole genome sequenced cell-free DNA are promising features for tumor-agnostic cancer detection. However, systematic biases challenge their cross-cohort generalization. We introduce LIONHEART, a novel, open source cancer detection method specifically optimized to generalize across datasets. The method correlates bias-corrected cfDNA fragment coverage across the genome with the locations of accessible chromatin regions from 487 cell and tissue types. We use these correlations to detect changes in the cell-free DNA cell type composition caused by cancer. We test LIONHEART on eight datasets and twelve cancer types (1083 non-cancer controls, 1251 cancers) obtained from different studies and show that it can distinguish cancer samples from non-cancer controls across cohorts with ROC AUC scores ranging from 0.59-0.91 (mean = 0.80, std = 0.11). We further validate the method on an external dataset, achieving a ROC AUC of 0.859.
Assessment of the implementation of iron and folic acid tablets supplementation to in-school girls in Nanumba South District of Northern Region, Ghana
Authors: Razak Nayina Bakunboa Isaac , Kogi Robert , Ndayishimiye Jean Claude , Opoku Samuel Yaw 
Published: November 2024

AbstractIron deficiency is a leading cause of morbidity and mortality among adolescent girls 10– 19 years of age globally. Despite the free weekly iron and folic acid supplementation, prevalence of anaemia among adolescent females still between 24% to 64.6%. This study sought to identify the factors affecting the implementation of iron and folic acid program to a school-based anaemia reduction in the Nanumba South District, Northern Region, Ghana.A cross-sectional analytical study was carried out. And a simple random sampling method was used to select the schools and the adolescent girls, while purposive sampling was used to select school health coordinators and health staff. The outcome variable was IFA compliance and exposures were knowledge on anaemia and IFAS program, as well as socio-demographic factors (Age, marital status, level of education, gestational age, parity, gestation age, and occupation). Adolescent girls who consumed at least five tablets of the expected dose in the previous 7 weeks (1 tablet per week) which is equivalent to consuming 70% of the expected dose before the day of the data collection were considered compliant. Respondents who were able to get “1” in all the four knowledge questions were considered to have good level of knowledge. Occupation level of parents was self-identified by the respondents. Multivariable logistic regression analysis was performed to identify the predictors of the outcome variable. Significance level was set at p<0.05.The level of knowledge about benefits of iron and folic acid supplementation was generally high in this study (88.0%). Overall, the majority (65.7%) of the respondents complied with iron and folic acid supplementation. Father’s occupational level was the only variable, which was significantly associated with adolescent girls’ IFA consumption compliance (p=0.002). The odds of compliance among respondents who were 17-25 years was significantly 56% times lower compared to those who were 10-16 years (AOR = 0.44 (95% CI: 0.21-0.96) p = 0.038). Adolescent girls of Kokomba ethnic group were also 83% less likely to comply with iron and folic acid consumption (AOR = 0.17 (95% CI: 0.03-0.89) p = 0.036).In conclusion, the study highlighted high compliance with the IFA among respondents, emphasizing the critical roles of teachers and health workers in counseling, monitoring, and supervision, while identifying age 17-25 years and Kokomba ethnic group being less significant factors influencing compliance. It is recommended that the role of teachers and health workers in the IFAS program should be strengthened, while addressing barriers to compliance among older adolescents and engaging families.
Evaluating malaria elimination strategies in military forces in Cambodia: a cluster-randomized clinical trial comparing monthly prophylaxis with focused screening and treatment
Authors: Wojnarski Mariusz , Chaudhury Sidhartha , Boonchan Threechada , Bun Rathvicheth , Chann Soklyda , Gosi Panita , Soveasna Kin , Song Sokhun , Buathong Nillawan , Ittiverakul Mali , Sriwichai Sabaithip , Arsanok Montri , Kuntawunginn Worachet , Saingam Piyaporn , Chaisatit Chaiyaporn , Ponlawat Alongkot , Fansiri Thanyalak , Vanachayangkul Pattaraporn , Jaichapor Boonsong , Sinoun Muth , Chuor Char Meng , Kheangheng Thay , So Mary , Wanja Elizabeth , Davidson Silas , Spring Michele , Rekol Huy , Dysoley Lek , Saly Kong , Livezey Jeffrey R. , Lin Jessica T. , Smith Philip L. , Satharath Prom , Manning Jessica E. , Sok Somethy , Saunders David L. 
Published: November 2024

AbstractBackgroundIdentifying effective malaria elimination strategies for remote forested regions in Southeast Asia is challenging given limited resources. In this study, two malaria elimination strategies were evaluated in partnership with the Royal Cambodian Armed Forces - monthly malaria prophylaxis (MMP) and focused screening and treatment (FSAT).MethodsEight primarily military clusters (1,050 volunteers total) along the Cambodian-Thai border were randomized to 3 months of MMP or FSAT with monthly malaria testing by RDT, PCR, and microscopy for six months. Clusters were sub-randomized to permethrin treated (ITU) or sham water-treated clothing (sITU). Volunteers in MMP clusters were given three full monthly dihydroartemisinin-piperaquine (DP) treatment courses with 12 weekly 22.5mg primaquine. Volunteers in FSAT clusters were treated with appropriate first-line antimalarials if malaria-positive by microscopy or PCR.ResultsPfpositivity in MMP clusters was reduced by 90% (10% at enrollment to 1% at 6 months; absolute risk reduction (ARR) 9%) at 6 months. However, 32% ofPfcases treated with DP as MMP at baseline recrudesced, requiring rescue treatment at 1 month with artesunate-mefloquine.Pfpositivity in FSAT clusters declined 66% over 6 months (7.6% to 2.7%; ARR 4.9%). MMP reducedPvpositivity from 9% to 0% at 3 months, butPvrebounded to 6.7% at 6 months. FSAT failed to significantly reducePvpositivity during the study. The 22.5mg weekly primaquine MMP regimen was safe, even for the 15% of volunteers with G6PD-deficiency. Those wearing ITU had additionalPvparasitemia reductions compared to sITU in the FSAT but not MMP groups. PCR was more sensitive than microscopy and RDT for detecting both species.ConclusionsMMP was safe, and superior to FSAT to reducePfandPv, suggesting greater utility to achieve malaria elimination in Cambodia. Low dose (22.5mg) weekly primaquine was a safe adjunct in this setting, even for those with G6PD-deficiency. Permethrin-treated clothing further reducedPvparasitemia for FSAT but not MMP. MMP may be more easily scaled to eliminate malaria. The military may provide substantial support for regional elimination efforts.
Env from EIAV vaccine delicately regulates NLRP3 activation via attenuating NLRP3-NEK7 interaction
Authors: Guo Xing , Liu Cong , Wang Yuhong , Li Hongxin , Ma Saiwen , Na Lei , Ren Huiling , Lin Yuezhi , Wang Xiaojun 
Published: November 2024

AbstractThe current equine infectious anemia virus (EIAV) vaccine causes attenuation of the inflammatory response to an appropriate level, compared to that produced by virulent EIAV. However, how the EIAV vaccine finely regulates the inflammatory response remains unclear. Using a constructed NLRP3-IL-1β screening system, viral proteins from two EIAV strains (the attenuated vaccine and its virulent mother strain) were examined separately. Firstly, EIAV-Env was screened to direct binding P2X7(R) with notable K+efflux trans-cellularly. Secondly, EIAV-Env was found to bind NLRP3 and/or NEK7 to trigger aggregation of NLRP3-NEK7 to form NLRP3-NEK7 complex in cells. Comparison of the two strains, we observed a significant reduction on vaccine-Env-initiated NLRP3-NEK7 complex formation, with no difference in Env triggering P2X7(R)-mediated ion fluxes. Thirdly, reciprocally mutation on four stable varied amino acids between two strains produced an anticipated outcome on NLRP3-IL-1β-axis activation. As the attenuated vaccine was shown evolved as a natural quasispecies of the virulent EIAV, its precise and adaptable regulation via spatial proximity-dependent intracellular activation might present a “win-win” virus-host adaption, offering an alternative strategy on HIV vaccine development.Author SummaryHere, we report that EIAV-Env mediates NLRP3 inflammasome activation through two distinct pathways. The first pathway involves a transcellular mechanism driven by K+ flux, which couples Env-P2X7 interaction. The second pathway entails direct intracellular binding between Env and NLRP3, promoting the assembly of NLRP3-NEK7 and subsequent inflammasome formation. Notably, we observed a marked difference in NLRP3 inflammasome activation between the vaccine and virulent strains, which was reflected in the extent of Env-mediated NLRP3-NEK7 aggregation. This study not only enhances our understanding of lentivirus-host immune interactions but also contributes to the broader discourse on virus evolution and host-induced inflammation.
The Growth Hormone-IGF-1 axis is a risk factor for Long-Term Kidney Allograft Failure
Authors: Cusick Matthew , Nair Viji , Fermin Damian , Hartman John , Beamish Jeffrey A. , Sun Zeguo , Zhang Zhongyang , Otto Edgar , Menon Rajasree , Nadimidla Sudha , Demchuk Nicholas , Shaffer Kelly , Heeger Peter , Zhang Weija , Menon Madhav C. , Kretzler Matthias , Wiggins Roger C. , Naik Abhijit S. 
Published: November 2024

AbstractIntroductionMaladaptive hypertrophy and podocyte stress and depletion contribute to kidney function decline. Although IGF-1 plays a key role in early hypertrophic responses in the single kidney state, its impact on KTx outcomes remains uncertain. This report tests the hypothesis that early IGF-1 exposure reduces KTx survival.MethodsPopulation datasets compared incident Death Censored Graft Failure (DCGF) rates by age at KTx (n=366,404) with IGF-1 levels by age (n=15,014). A clinical study of 216 KTx recipients evaluated the association of IGF-1 exposure with DCGF and secondary outcomes of proteinuria and Biopsy-Proven Acute Rejection. IGF-1 exposure was modeled using pre-KTx IGF-1 levels and donor kidney dose estimated from the donor:recipient body surface area ratio reflecting allograft hyperfiltration. The association of DCGF with an IGF1 SNP linked to high IGF-1 levels was assessed in 724 genotyped allograft recipients. Single-cell transcriptomic data from first-year post-KTx patients (n=14) and binephric donors (n=18) were compared to assess intrarenal cellular expression ofIGF1, IGF1R, and GHRtranscripts.ResultsDCGF risk by age at KTx paralleled IGF-1 levels by age. Higher IGF-1 exposure was associated with significantly increased risks of DCGF, proteinuria and T-Cell mediated rejection. Genotypic analysis showed a 50% increase in DCGF risk per risk allele at IGF1 eQTLrs35767. First-year biopsy results revealed no increase in intrarenalIGF1transcript, whileGHRandIGF-1Rtranscripts were suppressed, consistent with circulating IGF-1 (vs. graft-derived IGF-1) being the primary source of IGF-1 exposure.ConclusionWe identify a novel role for the GH-IGF-1 axis in reducing KTx survival.
Knowledge of healthcare workers in the domain of oncogenetics
Authors: Jabbour Jad , Habibian Léa , Martin Christine Anne-Marie , Diab Ernest , Kourié Hampig Raphaël 
Published: November 2024

AbstractBackgroundCancer is the second leading cause of mortality globally. 5-10% of cancer cases involve a genetic factor. Oncogenetics studies the role of genetic mutations in the development of cancer and plays a crucial role in understanding cancer pathogenesis and developing targeted therapies. Despite the critical nature of this field, the knowledge level among healthcare workers regarding oncogenetics, particularly in breast cancer, remains underexplored.ObjectiveThis study aimed to assess the knowledge of healthcare workers in oncogenetics, with a specific focus on breast cancer, to identify gaps and potential areas for educational intervention.MethodsA cross-sectional, web-based survey was conducted at a University Hospital. A questionnaire consisting of general and breast cancer-specific oncogenetics questions was distributed to nurses, medical interns, residents, and doctors. Responses were scored and analyzed to potentially identify statistically significant differences based on professional roles and experience.Results184 answers were recorded from which 89.67% confirmed familiarity with the term oncogenetics. Medical interns, residents, and doctors demonstrated significantly higher knowledge compared to nurses (p<0.001). The average scores indicated better general oncogenetics knowledge (mean=4.83/6) than breast cancer-specific knowledge (mean=3.77/6). Familiarity with oncogenetics correlated with higher scores across both sections (p<0.001). Notably, male participants outperformed females in breast cancer oncogenetics (p=0.02).ConclusionHealthcare workers displayed a satisfactory general knowledge of oncogenetics but showed significant gaps in breast cancer-specific knowledge. These findings highlight the need for targeted educational programs to enhance oncogenetics competency among healthcare workers, ensuring improved patient care. Future studies should evaluate the impact of such educational interventions on healthcare workers’ knowledge and practice.
Joint contact forces during barefoot, minimal and conventional shod running are highly individual
Authors: Kloock Lena , Arensmann Andrea , de Graaf Myriam , Gerlach Meike , Boström Kim , Wagner Heiko 
Published: November 2024

ABSTRACTThe supposed benefits of barefoot running are an often debated topic, with many studies investigating footwear influences on the kinematics and kinetics of running. Few studies, however, have analysed the effect on joint contact forces (JCFs). In this study, we investigated the influence of different footwear on the JCFs of the hip, knee, and ankle during running using a 3D musculoskeletal model. Kinematics were recorded from 16 volunteers while running on a treadmill at two speeds (2.0m/s and 2.5m/s) either barefoot (BF), wearing minimal shoes (MM), or normal shoes (NS). Alongside the JCFs, stride parameters and joint angles were examined using a generalised linear mixed model. Results showed a decrease in the hip JCF from BF to MM to NS, no consistent changes in the knee and an increase from BF to MM to NS at the ankle. However, these changes mostly had small effect sizes, so it’s unclear how relevant they are. The individual responses were much larger and showed opposite effects, indicating that the effects of footwear are highly individual and probably depend on the running style and characteristics of each runner.
A scoping review of guidelines on reporting and assessing dynamic mathematical models of infectious diseases
Authors: Chaturvedi Madhav , Bartz Antonia , Denkinger Claudia M , Klett-Tammen Carolina , Kretzschmar Mirjam , Kuhlmann Alexander , Lange Berit , Marx Florian M. , Mikolajczyk Rafael , Monsef Ina , Nguyen Hoa Thi , Suer Janik , Skoetz Nicole , Jaeger Veronika K , Karch André 
Published: November 2024

AbstractBackgroundMathematical models are essential for guiding public health policy decisions to combat the spread of infectious diseases. Nevertheless, there are no widely-used quality assessment tools that can be used to assess the quality of infectious disease modelling studies. There is also a lack of commonly accepted and used reporting guidelines that researchers can follow to improve the comprehensibility, transparency, and credibility of their publication. This scoping review identified common themes in existing reporting and quality assessment guidance for infectious disease modelling studies and adjacent fields of research.MethodsWe conducted temporally-unrestricted searches on Medline (via Ovid), Web of Science, medRxiv, and bioRxiv on January 4th, 2024 to find articles that provide guidance on writing or assessing modelling studies within infectious disease modelling and adjacent fields like health economics. Articles were double-screened for eligibility via title-and-abstract screening and full-text screening. Recommendations made by eligible articles were classified into 33 subdimensions which were categorised into seven dimensions (applicability; model structure; parameterisation and calibration; validity; uncertainty; interpretation; and reproducibility, clarity, and transparency). We followed the PRISMA extension for reporting scoping reviews.ResultsFifty-two articles were included in our final review. All dimensions except for interpretation were covered by most articles (79%-98%). However, we found substantial heterogeneity in the frequency with which subdimensions were addressed (12%-96%). Subdimensions pertaining to study design, assumptions about model structure, handling of parameter uncertainty, and transparency about parameter values were mentioned in most articles (85%-96%); conversely, discussions about auxiliary details regarding publication, software implementation, parsimony, and predictive validity were covered less frequently (23%-31%).ConclusionThis review reaffirms the lack of commonly used guidelines on reporting and assessing infectious disease models. Furthermore, it identifies common topics and recommendations from neighbouring fields which can inform the development of standardised guidelines for infectious disease modelling.
Early Measurable Residual Disease Detection after CAR-T is Associated with Poor Outcome Large B-cell Lymphoma Patients
Authors: Krasnow Nira , Maurer Katie , Song Catherine , Rhoades Justin , Xiong Kan , Crnjac Andela , Blewett Timothy , Gao Lily , Jacene Heather , Merryman Reid , Gohil Satyen H. , Duffy Caitlyn , Guerrero Liliana I. , Cruz Jamie Dela , McDonough Mikaela , Wolff Jacquelyn O. , Redd Robert , Mattie Mike , Miles Brodie , Makrigiorgos G. Mike , Neuberg Donna S. , Rodig Scott J. , Armand Philippe , Jacobson Caron , Adalsteinsson Viktor A. , Wu Catherine J. 
Published: November 2024

AbstractDespite responses of chimeric antigen receptor (CAR)-T cells in relapsed/refractory (R/R) large B cell lymphoma (LBCL) patients, over half of patients eventually relapse. Methods to detect early disease persistence are needed to identify patients at high-risk of treatment failure. We recently developed MAESTRO, an ultrasensitive, tumor-informed measurable residual disease (MRD) assay, which can detect parts-per-million (ppm) levels of circulating tumor DNA (ctDNA) using minimal sequencing. We applied MAESTRO to 140 samples from 28 patients (15 durable responders at 12 months, 13 nonresponders) to identify treatment failure following axicabtagene ciloleucel (axi-cel) administered at our institution between 2018 and 2022. Responder and nonresponder patients had similar baseline tumor burden. By 1 week after infusion, responders had marked ctDNA reduction compared to nonresponders, p<0.001. At weeks 2 and 4, responders had ctDNA levels approaching 0 ppm, while nonresponders had persistence of ctDNA, each p<0.001. At day 0, 21% of patients had ctDNA fractions below 0.01%, hence these individuals would not have qualified for ctDNA monitoring with a less sensitive test. Our results confirm feasibility of highly sensitive MRD detection by ctDNA for early identification of patients at high risk of disease progression from axi-cel.