bluuebunny/crossref_metadata_2025_split huggingface dataset:
STING Agonist VB-85247 Induces Durable Antitumor Immune Responses by Intravesical Administration in a Non–Muscle-Invasive Bladder Cancer
Authors: Prabagar Miglena G. , McQueney Michael , Bommireddy Venu , Siegel Rachael , Schieven Gary L. , Lu Ku , Husanov Ruziboy , Deepak Reema , Diller David , Huang Chia-Yu , Mordechai Eli , Eraslan Rukiye-Nazan 
Published: December 2024

Abstract
Bacillus Calmette–Guérin (BCG) is the current standard of care for non–muscle-invasive bladder cancer (NMIBC), but recurrence is common. Additional therapeutic options are a major unmet medical need for treating unresponsive patients. Stimulator of IFN genes (STING) plays a central role in mounting innate and adaptive immune responses to tumor cells, and activation of STING is a promising immunotherapeutic approach. In this study, we developed STING agonist VB-85247 for treating NMIBC by intravesical delivery as a strategy to provide a sustained period of exposure to bladder cancer cells while avoiding potential issues associated with intratumoral injection of STING agonists, which to date have shown only limited clinical efficacy. VB-85247 induced complete response in an orthotopic NMIBC model in contrast to treatment with BCG, which was not efficacious in the model. The efficacious dose was well tolerated and induced an immune response with immunologic memory that protected from rechallenge without further treatment. Activation of the STING pathway via VB-85247 induced upregulation of inflammatory cytokines IFNα/β, TNFα, IL6, and CXCL10, along with maturation and activation of dendritic cells. In addition, VB-85247 provided a therapeutic benefit in combination with immune checkpoint blockade using anti-PD-1 antibody treatment. Together, these preclinical data support the potential utility of VB-85247 for treating BCG-unresponsive patients with NMIBC and for enhancing the clinical benefit of potential of anti-PD-1 in bladder cancer. Based on these data, VB-85247 is being advanced into clinical development.
Significance: STING agonist VB-85247 administered by the intravesical route achieves prolonged tumor regression, induces immunologic memory, and provides additive benefits to anti-PD-1 treatment in non-muscle invasive bladder cancer.
Single-Cell RNA Sequencing before and after Light Chain Escape Reveals Intrapatient Multiple Myeloma Subpopulations with Divergent Osteolytic Gene Expression
Authors: Ohlstrom Denis , Walker Zachary J. , Pandey Abhishek , Davis Lorraine N. , Engel Krysta L. , Pan Zenggang , Forsberg Peter A. , Mark Tomer M. , Gillen Austin E. , Sherbenou Daniel W. 
Published: December 2024

Abstract
High-risk multiple myeloma is genomically unstable, comprising heterogeneous populations of tumor cells that evolve over time. Light chain escape (LCE) is a clinical phenomenon observed when light chains rise separately from M-spike values, which implies divergent tumor evolution. We sought to understand LCE by performing high-depth transcriptomic and phenotypic studies. We performed single-cell RNA-sequencing (scRNA-seq) and ex vivo drug sensitivity profiling on serial bone marrow biopsies from a patient with LCE at diagnosis, first relapse, and relapsed/refractory timepoints. scRNA-seq revealed distinct transcriptomic subpopulations with phenotypes that could be tracked separately by clinical serum light chain and M-spike values. Genes differentially expressed between subpopulations were assessed for generalizable effects on prognosis from the Multiple Myeloma Research Foundation CoMMpass and GSE24080 datasets. Notably, the LCE subpopulation exhibited gene expression profile featuring prominent LAMP5 overexpression, which was associated with risk for osteolytic bone lesions. Ex vivo drug sensitivity testing displayed differential sensitivity of the subpopulations. Copy number variant inference showed that the transcriptomic subpopulation underlying LCE was related to a genetic subclone that evolved over time. Our findings illustrate that malignant subpopulations underly LCE in multiple myeloma. These studies imply that LCE and LAMP5 gene overexpression portends for increased risk of osteolytic bone disease and adverse prognosis, findings that were confirmed in the subset of patients from the CoMMpass database with LCE.

Significance:
scRNA-seq was used to study a patient with high-risk multiple myeloma featuring LCE. LCE was rooted in a transcriptomic subpopulation that corresponded to a genetic subclone and established novel links between LCE and LAMP5 overexpression to osteolysis and prognosis, validated in RNA-seq databases.
Molecular Differences in Pancreatic Ductal Adenocarcinomas from Black versus White Patients
Authors: Mandal Saurabh , Teslow Emily A. , Huang Minxuan , Yu Yingying , Sridhar Swathi , Crawford Howard C. , Hockenberry Adam J. , Stoppler Melissa C. , Levin Albert M. , Huang Ling 
Published: December 2024

Abstract
Pancreatic cancer is the third leading cause of cancer-related death in the United States. Black or African American patients have a higher incidence of pancreatic cancer compared with other racial groups. It is unclear whether distinct molecular mechanisms are involved in the development of pancreatic cancer in different racial groups. To identify tumor molecular features that are distinctly associated with race in Black or African American and White patients with pancreatic ductal adenocarcinoma (the main subtype of pancreatic cancer), we analyzed deidentified patient records, including tumor sequencing data and expression of PD-L1, from the Tempus multimodal database. Patients with a primary diagnosis of pancreatic ductal adenocarcinoma and who received molecular testing between November 2017 and March 2023 were included in analyses. Among 4,249 patients analyzed in this study, 452 (10.6%) were Black or African American, and 3,797 (89.4%) were White. Black patients had a higher prevalence of TP53 mutations compared with White patients (P &lt; 0.001). KRASG12R mutations occurred more frequently in female patients in the Black versus White group (P = 0.007). Compared with White patients, Black patients had a higher tumor mutational burden (P &lt; 0.001) and PD-L1 overexpression (P = 0.047). In a separate analysis of recent clinical trials testing immunotherapies for pancreatic cancer, we found that Black patients and other minorities were underrepresented in most trials. These findings suggest race-associated molecular differences in tumors that may impact patient responses to immunotherapies. Our study also supports the importance of improving patient diversity in clinical trials on pancreatic cancer treatments.

Significance:
By analyzing the records of patients with pancreatic cancer in the Tempus multimodal database, we identified genomic mutations and PD-L1 overexpression occurred more frequently in Black patients compared with their White counterparts. These molecular features may contribute to racial disparities in pancreatic cancer.
Acute Infarct Core Volume Estimation on Noncontrast Computed Tomography With a Deep Learning Algorithm
Authors: Ortega‐Gutierrez Santiago , Vivanco‐Suarez Juan , Rodriguez‐Calienes Aaron , Salvia Victor , Galecio‐Castillo Milagros , Dibas Mahmoud , Lu Yujing , Rey Alba Garcia , Marti Cristian , Tanzi Leonardo , Hernandez‐Perez Maria , Jovin Tudor , Ribo Marc 
Published: December 2024

BACKGROUND
A simplified patient selection paradigm with noncontrast computed tomography (NCCT) can reduce the time to reperfusion and widen the eligibility of acute ischemic stroke large vessel occlusions (LVOs) for endovascular therapy. The objectives of this article are (1) to develop, train, and internally validate a deep learning algorithm that estimates baseline infarct core volume (ICV) on NCCT in anterior circulation LVO patients, and (2) by using an external set, to ascertain how this algorithm's (aICV‐NCCT) predictive performance compares with Alberta Stroke Program Early Computed Tomography Score‐NCCT and ICV‐CT perfusion in its capacity to estimate the final infarct volume established on diffusion‐weighted magnetic resonance imaging at 24‐ to 48‐hour follow‐up.

METHODS
In the first phase, stroke activations with baseline NCCT and CT angiography were used to train an aICV‐NCCT. The algorithm was then internally validated using intraclass correlations and Intersection over Union. In the external set, patients with LVO treated with endovascular therapy achieving modified Thrombolysis in Cerebral Infarction score ≥2b and available baseline NCCT, CT angiography, and CT perfusion were included.

RESULTS

A total of 2858 studies of patients with stroke alerts were used for training (80%) and internal validation (20%). We obtained a high correlation (intraclass correlation coefficient, 0.78; CI, 0.73–0.83) and an acceptable Intersection over Union of 0.24 on the internal validation set. The external set consisted on 230 patients with an LVO. When predicting final infarct volume on the external set, our aICV‐NCCT was similar to ICV‐CT perfusion (intraclass correlation coefficient, 0.50 versus 0.54;
P
= 0.764) and Alberta Stroke Program Early Computed Tomography Score‐NCCT (r
s
, −0.41;
P
= 0.436).

CONCLUSION
In this study, we developed and validated a deep learning algorithm that demonstrates an at least equivalent performance to CT perfusion in estimating core volume on acute stroke imaging studies in patients with suspected anterior circulation LVO strokes. The algorithm's robust performance holds significant potential in settings with limited access to advanced imaging technologies across diverse healthcare environments.
Uncertainty Hotspots in Global Hydrologic Modeling: The Impact of Precipitation and Temperature Forcings
Authors: Tang Guoqiang , Clark Martyn P. , Knoben Wouter J. M. , Liu Hongli , Gharari Shervan , Arnal Louise , Wood Andrew W. , Newman Andrew J. , Freer Jim , Papalexiou Simon Michael 
Published: December 2024

Abstract
Quantifying hydrologic modeling uncertainties originating from meteorological uncertainties is crucial yet unexplored on the global scale. This study integrates a novel ensemble meteorological dataset with process-based hydrologic models, assessing the impact of precipitation and temperature uncertainties across approximately three million subbasins globally. We introduce two metrics to identify uncertainty hotspots: one tracing the uncertainty propagation from inputs to model outputs and the other measuring the uncertainty magnitude relative to hydrologic climatology (i.e., ratio between uncertainty and climate average). Our findings reveal different uncertainty responses across hydrologic variables to the combined precipitation and temperature uncertainties. For routed river streamflow, uncertainty propagation is strong in tropical rain forests and Europe (except the Scandinavian Peninsula) but weak in the deserts, which is partly attributed to the regional differences in baseflow ratios. In contrast, both uncertainty metrics indicate low streamflow uncertainties in cryosphere areas and downstream areas of major rivers. The substantial modeling uncertainties observed, particularly in the Southern Hemisphere and less developed regions, underscore the need to improve global spatial meteorological datasets.
Neutrophil-To-Lymphocyte Ratio as a Prognostic Indicator in Thyroid Cancer
Authors: Gao Qiangang , Quan Mingming , Zhang Lilong , Ran Yanyun , Zhong Jijun , Wang Bin 
Published: December 2024

Objective In this study, we aimed to perform a comprehensive analysis to assess the prognostic value of neutrophil-to-lymphocyte ratio (NLR) levels in patients diagnosed with thyroid cancer. Methods We systematically searched multiple databases, including PubMed, the Cochrane Library, EMBASE, and Google Scholar, up until March 30, 2023, to identify relevant articles. The clinical outcomes evaluated in this study included overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), and cause-specific survival (CSS). Results This analysis includes 21 articles with 5187 patients in total. The pooled results revealed that patients with high NLR levels had significantly poorer OS (HR: 2.578, 95% CI: 2.050-3.242, P < 0.001), PFS (HR: 2.143, 95% CI: 1.616-2.843, P < 0.001), DFS (HR: 1.377, 95% CI: 1.045-1.816, P = 0.023), and CSS (HR: 2.842, 95% CI: 1.334-6.053, P = 0.007). The subgroup analyses were performed based on different study regions, treatment modalities, cancer types, and NLR cut-off values, and the above conclusion remained consistent in the majority of subgroup analyses. The stability and reliability of the aforementioned results were supported by the sensitivity analysis and publication bias test. Conclusion The baseline NLR levels were useful predictors of outcomes in patients with thyroid cancer.
Mechanical characteristics of bionic pseudostem-like multilayer weft-knitted spacer fabric for personal protection
Authors: Huang Yuqing , Dong Zhijia , Chen Chaoyu , Ma Pibo 
Published: December 2024

Inspired by the multi-layered structure found in banana pseudostem, an innovative bionic pseudostem-like multilayer weft-knitted spacer fabric (ML-WKSF) was proposed for the development of high-performance and mass-produced personal protective materials. ML-WKSFs with different spacer filament diameters (0.15, 0.175, and 0.2 mm) were produced on a computerized flat knitting machine, incorporating thermoplastic filaments during the knitting process to enhance structural supporting of the spacer filaments. In both flat compression and fatigue compression tests, the ML-WKSF with 0.15 mm filament exhibited superior compressive resistance and fatigue resistance due to the more compact fabric structure resulting from the smaller diameter monofilaments, which facilitated uniform stress distribution. Additionally, composite fabrics were prepared using a shear thickening fluid (STF) with a SiO2 mass fraction of 70%, and mechanical property tests were conducted. The composite fabrics displayed similar trends to the pure fabrics in both flat compression and fatigue compression tests. Differently, the integration of STF with the monofilaments led to an increase in compressive load bearing capacity. In low-velocity impact tests, larger spacer filaments resulted in better impact resistance for the fabrics as the impact force was locally dispersed. The composite with 0.2 mm spacer filaments demonstrated excellent impact resistance and energy absorption, achieving an energy absorption efficiency of 69% at an initial impact energy of 40 J.
Assessing institutional responsibility in scientific misconduct: A case study of enoximone research by Joachim Boldt
Authors: Wiedermann Christian J 
Published: December 2024

Background: Enoximone, a phosphodiesterase III inhibitor, was approved in Germany in 1989 and initially proposed for heart failure and perioperative cardiac conditions. The research of Joachim Boldt and his supervisor Gunter Hempelmann came under scrutiny after investigations revealed systematic scientific misconduct leading to numerous retractions. Therefore, early enoximone studies by Boldt and Hempelmann from 1988 to 1991 were reviewed. Methods: PubMed-listed publications and dissertations on enoximone from the Justus-Liebig-University of Giessen were analyzed for study design, participant demographics, methods, and outcomes. The data were screened for duplications and inconsistencies. Results: Of seven randomized controlled trial articles identified, two were retracted. Five of the non-retracted articles reported similarly designed studies and included similar patient cohorts. The analysis revealed overlap in patient demographics and reported outcomes and inconsistencies in cardiac index values between trials, suggesting data duplication and manipulation. Several other articles have been retracted. The analysis results of misconduct and co-authorship of retracted studies during Boldt’s late formative years indicate inadequate mentorship. The university’s slow response in supporting the retraction of publications involving scientific misconduct indicates systemic oversight problems. Conclusion: All five publications analyzed remained active and warrant retraction to maintain the integrity of the scientific record. This analysis highlights the need for improved institutional supervision. The current guidelines of the Committee on Publication Ethics for retraction are inadequate for large-scale scientific misconduct. Comprehensive ethics training, regular audits, and transparent reporting are essential to ensure the credibility of published research.
Impact of elbow stiffness on running economy in trained athletes
Authors: Wilk Cecilia , Besson Cyril , Stockton Laurie , Vauclair Frédéric , Gremeaux Vincent 
Published: December 2024

Background Elbow injuries are likely to generate a decreased range of motion (ROM), which might negatively affect athletic performance. To date, the effect of elbow stiffness on endurance running performance has never been studied. We conducted an observational, prospective, cross-over study to examine the impact of elbow stiffness on running economy. Methods Twenty trained athletes performed running economy tests at 12 km·h−1, with and without a limited elbow ROM (flexion: 90°, extension: 45°), imposed by a dynamic brace mimicking a severe elbow stiffness. Relative intensity and performance indexes were measured during a subsequent maximal incremental exercise test. Results Running economy was measured at 180 ± 10.6 mlO2·km−1·kg−1 with a full ROM, and 180.2 ± 12.3 mlO2·km−1·kg−1 with the limited ROM showing a non-significant 0.1% difference ( p = 0.871). Discussion Athletes experiencing post-traumatic elbow stiffness can find reassurance in knowing that it does not seem to impact a crucial metric of endurance running performance, namely running economy. Further research could explore elbow movement at different intensities of running, from higher aerobic speeds to sprinting.
Ankle and foot deformities and malformations in proximal femoral focal deficiency
Authors: Chomiak Jiri , Frydrychova Monika , Ošťádal Martin , Dungl Pavel 
Published: December 2024

Purpose: To describe foot abnormalities in proximal femoral focal deficiency and their correlation to the severity. Methods: Eighty-nine extremities in 87 patients were evaluated between 1996 and 2020 clinically and radiologically. Fibula length, ankle shape, tarsal coalitions, and the number of foot rays were recorded. Extremities with proximal femoral focal deficiency were classified according to Pappas and divided into severe (classes II and V), medium severe (classes III and IV), and mild groups (classes VII, VIII, and IX). Results: The fibula was short in 89% and absent in 11% of cases. An absent fibula occurred mostly in severe class III and only in 4% of mild grades (statistically significant, p = 0.004). The valgus ankle joint prevailed in 82% of cases. Spherical ankle joints (18% of cases) were associated in all cases with a tarsal coalition. Tarsal coalitions occurred in 14.6% and were present in all classes except class IV. Five ray feet were found in 83% of cases, four ray feet were found in 16%, and three ray feet in one extremity. Reduction in the number of foot rays occurred more commonly in association with fibular aplasia (30%). Conclusions: Abnormalities of the fibula and ankle joint represent a constant part of proximal femoral focal deficiency, whereas tarsal coalition and a reduction of foot rays do not. The severity of foot abnormalities does not correlate to the severity of proximal femoral focal deficiency but does with fibular aplasia.
Endoscopic assessment of gastric emptying in older adults after preoperative administration of 5% glucose solution: a randomized controlled study
Authors: Liu Yan , Yu Qian , Wang Run , Luo Linli 
Published: December 2024

Abstract
Background
Delayed gastric emptying of liquids may heighten the risk of aspiration reflux in elderly individuals. To investigate the gastric emptying of an oral supplement containing 5% dextrose solutions before sedation for gastroscopy.

Patients and methods
A total of 100 elderly patients who were scheduled for elective gastroscopy were randomly assigned to two groups: the NPO(nil per os ) group and the dextrose solution ingestion group, which ingested a 5% dextrose solution (5 ml/kg) two hours before the procedure. The primary outcome measure was the gastric volume (GV) suctioned and measured during the gastroscopic examination. Secondary outcome measures included GV per weight (GV/kg), post-discharge blood glucose levels, patient discomfort assessed using the Visual Analog Scale (VAS), clarity of gastric mucosal visualization during gastroscopy, and the incidence of adverse events. Additionally, linear regression analysis was employed to identify factors influencing gastric volume.

Results
There were no significant differences in gastric volume (GV) (P=0.258) and GV per weight (GV/W) (P=0.137) between the NPO group and the dextrose solution group. However,the NPO group had higher discomfort scores on the Visual Analog Scale compared to the dextrose solution group, with a statistically significant difference(P<0.001). The clarity of gastric mucosal visualization during gastroscopy was also significantly different between the two groups(P=0.038). Blood glucose levels and the incidence of adverse events showed no significant differences between the two groups.Multivariate linear regression analysis revealed that younger age and higher functional dyspepsia symptom diary (FDSD) scores were associated with larger gastric volume, with the regression equation being: GV = 79.922 - 1.186 $$\times$$
×
age + 0.556 $$\times$$
×
FDSD.

Conclusion
In elderly patients, drinking 5 ml/kg of a 5 % glucose solution two hours prior to gastroscopy does not significantly increase gastric volume compared to midnight fasting.

Trial registration
ChiCTR2100047031 (date of registration: 7 June 2021).