bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I trial comparing bile acid and short-chain fatty acid alterations in stool collected from human subjects treated with omadacycline or vancomycin
Authors: Jo Jinhee , Hu Chenlin , Horvath Thomas D. , Haidacher Sigmund J. , Begum Khurshida , Alam M. Jahangir , Garey Kevin W. 
Published: January 2025

ABSTRACT

Omadacycline, an aminomethylcycline tetracycline, has a low propensity to cause
Clostridioides difficile
infection (CDI) in clinical trials. Omadacycline exhibited a reduced bactericidal effect compared with vancomycin on key microorganisms implicated in bile acid homeostasis and short-chain fatty acids (SCFAs), key components of CDI pathogenesis. The purpose of this study was to assess bile acid and SCFA changes in stool samples from healthy volunteers given omadacycline or vancomycin. Stool samples were collected daily from 16 healthy volunteers, who were given oral omadacycline or vancomycin for 10 days. Daily stool samples were assessed for bile acids and SCFA concentrations using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Bile acids changed significantly over time for all subjects (
P
< 0.01 for each bile acid), with vancomycin causing a larger change in the primary bile acids, cholic acid (
P
< 0.001) and chenodeoxycholic acid (
P
< 0.001), and a reduced change in the secondary bile acid, lithocholic acid (
P
< 0.001). The secondary bile acid ursodeoxycholic acid was reduced less by vancomycin than by omadacycline (
P
< 0.001). All SCFA concentrations were reduced from baseline with a larger effect observed with vancomycin for isobutyric acid (
P
= 0.0034), propionic acid (
P
= 0.0012), and acetic acid (
P
= 0.047). Microbial changes associated with the use of vancomycin versus omadacycline were also associated with changes in bile acid homeostasis and SCFA concentrations. Oral omadacycline produced a distinctive metabolomic profile compared with vancomycin when administered to healthy subjects. The metabolic findings help further our understanding of the lower CDI risk properties of omadacycline and warrant phase 2 investigations using omadacycline as a CDI antibiotic.

IMPORTANCE
The purpose of this study was to assess bile acid and SCFA changes in stool samples obtained from healthy volunteers given omadacycline or vancomycin. Stool samples were collected daily from 16 healthy volunteers given a 10-day oral course of omadacycline or vancomycin. Vancomycin caused a larger change in the primary bile acids and SCFA concentrations compared with omadacycline. The metabolic findings help further our understanding of the mechanistic basis for the lower-risk properties of omadacycline causing CDI and warrant phase 2 investigations using omadacycline as a CDI antibiotic.

CLINICAL TRIALS

This study is registered with

ClinicalTrials.gov
as
NCT06030219

.
The impact of FDA-cleared molecular solutions for BK polyomavirus quantitation
Authors: Parikh Bijal A. , Anderson Neil W. 
Published: January 2025

ABSTRACT

Accurate detection and monitoring of BK polyomavirus (BKV) infection is of critical importance in the post-transplant period, guiding treatment decisions that balance the anti-rejection effects of immune suppression with host-protective effects of immune defense. Historically, test methods for BKV have been independently developed by laboratories to address this unmet need. However, these assays can suffer from inconsistencies in analytical variability, which in turn have hindered the establishment of commutable and clinically actionable viral load thresholds for clinical management. As a result, the interpretation of viral load quantitation has not been standardized across transplant centers for the purpose of monitoring patients at highest risk for infection-related complications. In this review, we describe challenges that have historically limited widespread adoption of BKV quantitative testing. We then detail how developments in the field, including optimized amplicon selection, the introduction of an international standard, and the availability of Food and Drug Administration (FDA)-cleared methods, have played a role in harmonization of quantitative BKV measurements in the clinical management of transplant recipients.
Heat-related impacts on all-cause emergency hospitalisation differ by area deprivation and urbanicity: a time-stratified case-crossover study in Japan
Authors: Nishimura Hisaaki , Nawa Nobutoshi , Nakaya Tomoki , Fushimi Kiyohide , Fujiwara Takeo 
Published: January 2025

BackgroundClimate-related health impacts have been a global public health concern. Identifying vulnerable populations is critical in implementing adaptation strategies. This study aimed to examine how heat-related impacts on all-cause emergency hospitalisations differ by area deprivation and urbanicity.MethodsAll-cause emergency hospitalisations were identified in the Japanese nationwide administrative database during the warm season between 2011 and 2019. A time-stratified case-crossover study was conducted to examine short-term associations between daily mean temperature and hospitalisation. Days of heat exposure were defined as days when the daily mean temperature exceeded the minimum morbidity temperature (ie, temperature with the lowest relative risk between the 25th and the 75th percentiles of the daily mean temperature distribution). Analyses were stratified by area deprivation index and urbanicity. Heat-related excess hospitalisations were quantified using the population attributable fraction (PAF), derived as a fraction of heat-attributable emergency hospitalisations to the total number of emergency hospitalisations for all study subjects or within specific subgroups.ResultsWe identified 5 914 084 hospitalisations. Among all study subjects, PAF for heat-related excess hospitalisations was 1.69% (95% CI 1.54% to 1.87%). PAF for heat-related excess hospitalisations was more pronounced in people living in the most deprived areas (1.87%, 95% CI 1.68% to 2.06%) than those in the least deprived (1.19%, 95% CI 0.98% to 1.41%) and in urban populations (2.03%, 95% CI 1.78% to 2.30%) than rural ones (1.42% (95%CI 1.24% to 1.60%)). When further stratified by deprivation and urbanicity simultaneously, PAF for heat-related excess hospitalisations was most significant among urban populations living in the most deprived areas (2.62%, 95% CI 2.26% to 3.03%).ConclusionThese findings revealed that individuals living in the most deprived areas in urban settings were particularly vulnerable to heat exposure. Adaptation strategies tailored to socioeconomic and geographical inequalities can potentially reduce future heat-related health impacts.
A cultivar/soil selection protocol for simulating weather impacts on regional crop yield
Authors: Simon Kemp I. , Warland Jon S. 
Published: January 2025

Crop yield simulation can facilitate understanding and support policy response to climate warming. DSSAT modelling is dependable when the crop varieties characterised can manifest realistic yield-responses to weather and hence climate, in a location of interest. We strived to minimise field trial and cultivar calibration resources. Our primary objective was to identify in-built DSSAT cultivars, which when used with representations of local soils can simulate the observed maize and soybean yields of 1987–2016, across 12 counties in Southwestern Ontario. These cultivars/soils were then utilised to disaggregate historic weather contribution to trending yields, but they can otherwise serve climate projection impact studies, as envisioned. Technology had contributed to progressive time-based increases in measured yields. Hence, a mixed nRMSE and r2 factor (MSF ≤ 1) enabled quick and decisive cultivar/soil selections, conditioned on closer matching simulated yield levels and variations with measured. Pio-3563 (maize) and Pio-9202 (soybean) were among the cultivars selected. Northern and southern subregional composites of simulated county yields, from final selections, compared with measured at nRMSE ≤ 0.20 and r2 ≥ 0.53, the best values being nRMSE ≈ 0.08 with r2 ≈ 0.80 (soybean) in the south. Modelling indicated 60% and 52% climate warming contributions to increased maize and soybean yields, respectively, across Southwestern Ontario. These percentages mostly agreed with those of other investigators using statistical methods for weather impact evaluations, which were utilised for final validation of our selections. An additional finding was that northern weather contributed 35%, while southern weather contributed 70% to increased subregional soybean yields.
Computing Hamiltonian Paths with Partial Order Restrictions
Authors: Beisegel Jesse , Ratajczak Fabienne , Scheffler Robert 
Published: January 2025

When solving the Hamiltonian path problem it seems natural to be given additional precedence constraints for the order in which the vertices are visited. For example, one could decide whether a Hamiltonian path exists for a fixed starting point, or that some vertices are visited before another vertex. We consider the problem of finding a Hamiltonian path that observes all precedence constraints given in a partial order on the vertex set. We show that this problem is
NP
-complete even if restricted to complete bipartite graphs and posets of height 2. In contrast, for posets of width
k
there is a known

\(\mathcal {O}\)

(
k
2
n

k

) algorithm for arbitrary graphs with
n
vertices. We show that it is unlikely that the running time of this algorithm can be improved significantly, i.e., there is no
f(k) n

o(k)

time algorithm under the assumption of the Exponential Time Hypothesis. Furthermore, for the class of outerplanar graphs, we give an

\(\mathcal {O}\)

(
n
2
) algorithm for arbitrary posets.
Community Engagement to Inform Multilevel Analyses of the Role of Neighborhood Factors in Cancer Control Behaviors in African Americans
Authors: Knott Cheryl L. , McCullers Asli , Woodard Nathaniel , Aldana Valerie , Williams Beverly R. , Clark Eddie M. , Schootman Mario , Park Crystal L. , He Xin , Ghosh Debarchana 
Published: January 2025

Abstract

Background:
Although community engagement has had a substantial presence in public health research, community input to inform geospatial and health analyses remains underutilized and novel. This article reports on community engagement activities to solicit stakeholder perspectives on the role of neighborhood conditions in health and cancer. We discuss how this community input refined an a priori conceptual model to be tested in the larger Families, Friends, and Neighborhoods Study.

Methods:
We conducted semistructured virtual interviews with 82 stakeholders (e.g., community and faith leaders, educators, and healthcare workers) across four states (Maryland, Connecticut, Alabama, and Missouri). Participants discussed the impact where a person lives can have on their health and cancer risk. We subsequently convened a virtual group discussion with 17 randomly selected interviewees. Our study team individually reviewed discussion notes, which were synthesized into a consensus document.

Results:
In addition to constructs from the original conceptual model, participants identified neighborhood-level factors not present in the original model, including K-12 educational quality, local property investment, homelessness, public transportation infrastructure, proximity to healthcare facilities, environmental toxin exposures, access to healthy foods, and cost of living. These factors will be incorporated into the Families, Friends, and Neighborhoods Study analytic models.

Conclusions:
Although geospatial analyses in health research have not traditionally employed community engagement techniques, this study illustrates the value of informing multilevel analytic models with the lived experiences of those negatively affected by neighborhood conditions that underlie the risk, prevention, and screening behaviors driving cancer incidence and mortality.

Impact:
Future social epidemiology research can be enriched through community engagement.
The FBXO45-GEF-H1 axis controls germinal center formation and B-cell lymphomagenesis
Authors: Sahasrabuddhe Anagh A. , Chen Xiaofei , Ma Kaiyu , Wu Rui , Liang Huan-Chang , Kapoor Richa , Chhipa Rishi R. , Onder Ozlem , McFetridge Courtney , Van Arnam John S. , Zhang Xiao , Morrissette Jennifer J.D. , Pillai Vinodh , Li Marilyn M. , Szankasi Philippe , Basrur Venkatesha , Conlon Kevin P. , Raabe Tobias D. , Bailey Nathanael G. , Hogaboam Cory M. , Rottapel Robert , Kim Junhyong , López Cristina , Schlesner Matthias , Siebert Reiner , Dreval Kostiantyn , Morin Ryan D. , Moro Loredana , Pagano Michele , Staudt Louis M. , Lim Megan S. , Elenitoba-Johnson Kojo S.J. 
Published: January 2025

Abstract
The role of ubiquitin-mediated degradation mechanisms in the pathogenesis of diffuse large B cell (DLBCL) and follicular lymphoma (FL) is not completely understood. We show that conditional deletion of the E3 ubiquitin ligase Fbxo45 in germinal center B-cells results in B-cell lymphomagenesis in homozygous (100%) and heterozygous (48%) mice. Mechanistically, FBXO45 targets the RHO guanine exchange factor ARHGEF2/GEF-H1 for ubiquitin-mediated degradation. Double genetic ablation of Fbxo45 and Arhgef2 ameliorated lymphoma formation. Transgenic knock-in mice harboring a GEF-H1 mutant unable to bind FBXO45 develop B-cell lymphomas with ~50% penetrance. Genome sequencing in human lymphomas identified mutually-exclusive FBXO45 copy number losses and ARHGEF2 gains, with combined frequencies ranging from 26.32% in FL to 45.12% in DLBCL. Notably, FBXO45 silencing enhances sensitivity to MEK1/2 inhibition. These results identify FBXO45 and ARHGEF2 as a novel tumor-suppressor and oncogene pair involved in the pathogenesis of B-cell lymphomas with significant implications for targeted therapies.
Comparative Effects of Glenzocimab and Eptifibatide on Bleeding Severity in 2 Mouse Models of Intracranial Hemorrhage
Authors: Dupont Sébastien , Lebas Héloïse , Mavouna Sabrina , Pascal Eloïse , Perrot Astride , Cogo Adrien , Bourrienne Marie‐Charlotte , Farkh Carine , Solo Nomenjanahary Mialitiana , Ollivier Véronique , Zemali Fatima , Nieswandt Bernhard , Loyau Stéphane , Jandrot‐Perrus Martine , Camerer Eric , Desilles Jean‐Philippe , Mazighi Mikael , Boulaftali Yacine , Ho‐Tin‐Noé Benoît 
Published: January 2025

Background
Antiplatelet drugs represent potential candidates for protecting the penumbral microcirculation during cerebral ischemia and improving the benefits of arterial recanalization in ischemic stroke. Yet while the efficacy of such adjuvant strategies has been shown to be highly time dependent, antiplatelet therapy at the acute phase of ischemic stroke cannot be envisioned until the diagnosis of stroke and its ischemic nature have been confirmed because of the presumed risk of worsening bleeding in case of intracranial hemorrhage (ICH). Here, we investigated this risk for 2 antiplatelet drugs currently being tested in clinical trials for ischemic stroke, glenzocimab and eptifibatide, in 2 mouse models of ICH.

Methods and Results
The severity of ICH was assessed in mice humanized for glycoprotein VI treated or not with glenzocimab or eptifibatide at effective dose, in a model of primary ICH caused by unilateral striatal injection of collagenase type VII, and in a model of hyperglycemia‐induced hemorrhagic transformation of cerebral ischemia–reperfusion injury. Glenzocimab had no impact on bleeding severity in either model of ICH. Conversely, eptifibatide caused a significant increase in intracranial bleeding in both models, and a drastic increase in death after hyperglycemia‐induced hemorrhagic transformation of cerebral ischemia–reperfusion injury.

Conclusions
Unlike eptifibatide, glenzocimab is safe in the setting of ICH. These results suggest that glenzocimab could be administered upon suspicion of ischemic stroke, before assessment of its ischemic nature, thus opening the way to hastening of treatment initiation.
Talimogene laherparepvec (T-VEC) as a treatment for melanoma: A systematic review
Authors: Alla Sai Santhosha Mrudula , Tekuru Yogesh , Lokesh Moraboina Sai , Alla Deekshitha , Tvisha Patel , Tirupati Soujanya , Singh Aradhya , Tejaswini Yeshala , Mahmood Mariya , Siingh Nanki Pratap , Vineetha Bodipudi 
Published: January 2025

Background and aims Melanoma now presents an average risk of 1 in 50 in the Western world. Talimogene laherparepvec (T-VEC), an FDAapproved oncolytic virus derived from Herpes Simplex Virus type 1 (HSV-1), has proven effective in reducing morbidity and mortality from melanoma but causes adverse effects like chills, fever, exhaustion, and injection site discomfort. Research focuses on combining T-VEC with immune checkpoint inhibitors, such as pembrolizumab, to enhance its efficacy and broaden its application. Methods A systematic search was conducted using PubMed, Scopus, Web of Science, Google Scholar, and ProMED, adhering to PRISMA guidelines. Results were tabulated and analyzed. Results This review included 15 studies comprising nine cohorts, four case reports, a case series, and a randomized control trial, involving 779 melanoma patients in stages IIIB to IV, 58% of whom were male with a mean age of 65 years. Treatment duration with T-VEC averaged 35.07 weeks, with dosages ranging from 10^6 to 10^8 PFU/ml. The intervention yielded a mean DRR of 41.87% and an ORR of 62.2%. The most common side effect was chills, affecting 21.69% of participants. Pyrexia was reported by 20.41% of participants, followed by influenzalike illness (14.89%). Conclusion T-VEC effectively improves ORR and DRR in melanoma patients. However, further research is needed on combination therapy prospects and its adverse effects.
MGATAF: multi-channel graph attention network with adaptive fusion for cancer-drug response prediction
Authors: Saeed Dhekra , Xing Huanlai , AlBadani Barakat , Feng Li , Al-Sabri Raeed , Abdullah Monir , Rehman Amir 
Published: January 2025

Abstract

Background
Drug response prediction is critical in precision medicine to determine the most effective and safe treatments for individual patients. Traditional prediction methods relying on demographic and genetic data often fall short in accuracy and robustness. Recent graph-based models, while promising, frequently neglect the critical role of atomic interactions and fail to integrate drug fingerprints with SMILES for comprehensive molecular graph construction.

Results
We introduce multimodal multi-channel graph attention network with adaptive fusion (MGATAF), a framework designed to enhance drug response predictions by capturing both local and global interactions among graph nodes. MGATAF improves drug representation by integrating SMILES and fingerprints, resulting in more precise predictions of drug effects. The methodology involves constructing multimodal molecular graphs, employing multi-channel graph attention networks to capture diverse interactions, and using adaptive fusion to integrate these interactions at multiple abstraction levels. Empirical results demonstrate MGATAF’s superior performance compared to traditional and other graph-based techniques. For example, on the GDSC dataset, MGATAF achieved a 5.12% improvement in the Pearson correlation coefficient (PCC), reaching 0.9312 with an RMSE of 0.0225. Similarly, in new cell-line tests, MGATAF outperformed baselines with a PCC of 0.8536 and an RMSE of 0.0321 on the GDSC dataset, and a PCC of 0.7364 with an RMSE of 0.0531 on the CCLE dataset.

Conclusions
MGATAF significantly advances drug response prediction by effectively integrating multiple molecular data types and capturing complex interactions. This framework enhances prediction accuracy and offers a robust tool for personalized medicine, potentially leading to more effective and safer treatments for patients. Future research can expand on this work by exploring additional data modalities and refining the adaptive fusion mechanisms.
Natural and sexual selection and functional roles influence colouration but not the amount of variation in butterfly wing colour patterns
Authors: Dharmaraaj Bhavya , Kunte Krushnamegh 
Published: January 2025

Abstract

Background
Trait variation is shaped by functional roles of traits and the strength and direction of selection acting on the traits. We hypothesized that in butterflies, sexually selected colouration is more variable owing to condition-dependent nature and directional selection on sexual ornaments, whereas naturally selected colouration may be less variable because of stabilising selection. We measured reflectance spectra, and extracted colour parameters, to compare the amount of variation in sexually versus naturally selected colour patches across wing surfaces and sexes of 20 butterfly species across 4 families (Nymphalidae, Papilionidae, Pieridae, Lycaenidae).

Results
We found that: (a) males had more conspicuous, i.e., brighter and more saturated colour patches compared with females (as expected of sexually selected traits but not necessarily of naturally selected traits), and (b) dorsal surfaces in both sexes had more conspicuous sexual ornaments as well as protective (aposematic/mimetic) colour patches on darker wing backgrounds, compared with ventral surfaces. However, colour patches did not differ in the amount of variation either in selection (ecological/sexual functions), sex or wing surface-specific manner.

Conclusions
These findings show that functional roles and selection influence colour parameters but not the amount of variation in butterfly wing colour patterns.
Blood pressure control with active ultrafiltration measures and without antihypertensives is essential for survival in hemodiafiltration and hemodialysis programs for patients with CKD: a prospective observational study
Authors: Mora-Bravo Franklin Geovany , Torres Pamela Tatiana Morales , Campoverde Nelson Rojas , Carcelen Guillermina Lucía Blum , Mancheno Juan Cristobal Santacruz , Tipanta Ángel Cristóbal Santacruz , Perez-Grovas Hector , Abarca Willan Patricio Robles 
Published: January 2025

Abstract

Background
High blood pressure is a prevalent condition in patients with chronic kidney disease on hemodialysis. Adequate control of high blood pressure is essential to reducing deaths in this group. The present study aimed to observe mortality prospectively in a group of patients in hemodialysis and hemodiafiltration programs in whom the use of antihypertensives was optimized with the point-of-care dry weight (POC-DW) technique.

Methods
The present observational, prospective study was carried out at the Pafram hemodiafiltration unit in Morona Santiago, Ecuador, and the hemodialysis unit of the Fundación Renal del Ecuador in Guayaquil, Ecuador, from August 2019 to December 2023. Patients who were receiving hemodiafiltration were included. Weight was optimized with POC-DW for eight weeks. In Group 1, patients whose use of antihypertensive drugs was not required to control systolic blood pressure with a value less than 150 mmHg predialysis, less than 130 mmHg postdialysis, and a peridialytic blood pressure (defined as post-HD minus pre-HD SBP) between 0 and − 20 mmHg were analyzed. In Group 2, patients who required antihypertensive drugs for not meeting the aims of systolic blood pressure were included. The variables included clinical, demographic, mortality, description of the treatment, and routine laboratory tests in dialysis programs. The sample was nonprobabilistic. Survival analysis was performed for the study groups. The log-rank test (Mantel-Cox) was used for survival comparisons.

Results
The study included 106 patients. Optimal blood pressure control without antihypertensive treatment was achieved in 52 patients (49.1%) (Group 1). In 54 patients (50.9%), antihypertensive agents were required (Group 2). There was more significant mortality in the group that received antihypertensives: 11 patients in group 1 (21.2%) versus 25 patients in group 2 (46.3%) (P = 0.005). Survival was more significant in group 1, with an HR of 2.2163 (1.125–4.158) (P = 0.0243).

Conclusion
In hemodiafiltration and hemodialysis programs, blood pressure control with active ultrafiltration measures and without using antihypertensives is essential for survival in patients with CKD.