bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase 1 clinical trial of B-Cell Maturation Antigen (BCMA) NEX-T® Chimeric Antigen Receptor (CAR) T cell therapy CC-98633/BMS-986354 in participants with triple-class exposed multiple myeloma
Authors: Ravi Gayathri , Richard Shambavi , Kumar Shaji , Atrash Shebli , Liedtke Michaela , Kaur Gurbakhash , Derman Benjamin , Bergsagel P. Leif , Mailankody Sham , McCarthy Philip , Shrestha Alok , Kelly Lisa M. , Ly Thomas , Das Sharmila , Thorpe Jerill , Maier Alison , Varun Divya , Navarro Garnet , Burgess Michael R. , Hege Kristen , Koegel Ashley K. , Costa Luciano J. 
Published: February 2025

Abstract
BCMA-targeted CAR T-cells transformed the treatment of relapsed and refractory multiple myeloma (RRMM), yet improvements are needed in manufacturing, toxicity and efficacy. We conducted a phase 1 clinical trial of BMS-986354, an autologous BCMA CAR T manufactured using an optimized NEX-T® process, in participants with triple-class exposed, RRMM. The 65 participants had a median of 5 (range 3–13) prior regimens, 39% had cytogenetic high-risk, 91% triple-class refractory, and 43% extra-medullar disease. Part A (dose-escalation) of the study enrolled participants in cohorts receiving 20 (N = 7), 40 (N = 24), or 80 (N = 11)x 106 CAR + T-cells. In part B (expansion), an additional 23 participants were treated at the recommended phase 2 dose, 40 ×106 CAR + T cells. Across dose levels, cytokine release syndrome (CRS) occurred in 82% (2% grade ≥3), neurotoxicity in 8% (2% grade ≥3), and infections in 32% of participants (5% grade ≥ 3). The response rate was 95%, with 46% achieving complete responses. Median progression-free survival was 12.3 months (95% CI 11.3–16). Compared to orvacabtagene autoleucel (same CAR construct, conventional manufacturing), BMS-986354 had higher proportion of T central memory cells, were less differentiated and had enhanced potency and proliferative capacity, supporting the use of NEX-T® in future CAR T development.
Exploring BCL2 regulation and upstream signaling transduction in venetoclax resistance in multiple myeloma: potential avenues for therapeutic intervention
Authors: Fonseca Rodrigo , Zhu Yuan Xiao , Bruins Laura A. , Ahmann Joseph , de Bonolo Campos Cecilia , Braggio Esteban , Chen Xianfeng , Arribas Mariano , Darvish Susie , Welsh Seth , Meermeier Erin , Mangalaparthi Kiran K. , Kandasamy Richard K. , Ahmann Greg , Wiedmeier-Nutor J. Erin , Pandey Akhilesh , Chesi Marta , Bergsagel P. Leif , Fonseca Rafael 
Published: February 2025

Abstract
Investigating venetoclax (VTX) resistance in multiple myeloma (MM) is crucial for the development of novel therapeutic strategies to tackle resistance. We conducted a multi-omic characterization of established VTX-resistant isogenic human myeloma cell lines (HMCL) and primary MM patient samples pre- and post-VTX treatment. Transcriptomic and proteomic analysis revealed that resistance was largely associated with BCL-2 family protein dysregulation, including upregulation of anti-apoptotic proteins such as MCL-1, BCL-XL, BCL-2, and downregulation of pro-apoptotic members. Notably, the re-introduction of BIM into resistant cells restored VTX sensitivity and synergized with MCL-1 inhibitors. Upstream signaling pathways, including growth factor receptor tyrosine kinase (RTK) and phosphoinositide-3-kinase (PI3K) were implicated in this dysregulation. Simultaneous inhibition of MCL-1, BCL-XL, and upstream PI3K, RTK (FGF, EGF, and IGF1) mediated signaling enhanced VTX sensitivity. Post-translational modifications of MCL-1, particularly its stabilization via acetylation and phosphorylation, were investigated, although their inhibition only marginally increased VTX sensitivity. Lastly, the inhibition of AURKA and mitochondrial respiration also improved VTX sensitivity in some resistant HMCLs. Our findings suggest that combining VTX with MCL-1 and BCL-XL inhibitors or PIK3/RTK inhibitors holds potential for overcoming resistance. The study illustrates the importance of understanding molecular determinants of resistance to develop tailored therapeutic strategies.
Cell-associated galectin 9 interacts with cytotoxic T cells confers resistance to tumor killing in nasopharyngeal carcinoma through autophagy activation
Authors: Kam Ngar-Woon , Lau Cho Yiu , Lau Jeffrey Yan Ho , Dai Xin , Liang Yusi , Lai Syrus Pak Hei , Chung Michael King Yung , Yu Valen Zhuoyou , Qiu Wenting , Yang Mengsu , Smith Corey , Khanna Rajiv , Ng Kwan Ming , Dai Wei , Che Chi Ming , Lee Victor Ho-Fun , Kwong Dora L. W. 
Published: February 2025

Abstract
Immune effector cells, including cytotoxic T lymphocytes (CTLs) play essential roles in eliminating cancer cells. However, their functionality is often compromised, even when they infiltrate the tumor microenvironment (TME) or are transferred to cancer patients adoptively. In this study, we focused on galectin 9 (G9), an inhibitory ligand that we observed to be predominately positioned on the plasma membrane and readily interacts with CD8 + CTL in the TME of nasopharyngeal carcinoma (NPC). We discovered that cell-cell contact between activated effector CTLs and target tumor cells (TarTC) with G9 overexpression led to cellular death defects. Despite the formation of CTL–TarTC conjugates, there is no impact on the cell number nor viability of CTL, and the release of cytolytic content and associated activity were not completely abrogated. Instead, this interaction promoted autophagy and restricted necrosis in the TarTC. Furthermore, reducing G9 expression in tumor cells enhanced the suppressive effect on tumor growth upon adoptive transfer of activated effector CTL. Additionally, inhibiting autophagy effectively controlled tumor growth in cases of G9 overexpression. Therefore, we highlight the contribution of G9 in facilitating the resistance of NPC to CTL-mediated killing by inducing a selection-cell death state in tumor cells, characterized by increased autophagy and decreased necrosis.
A Markov model assessing the cost-effectiveness of various anti-vascular endothelial growth factor drugs and panretinal photocoagulation for the treatment of proliferative diabetic retinopathy
Authors: Luckham Kirsty , Tebbs Hannah , Claxton Lindsay , Burgess Philip , Dinah Christiana , Lois Noemi , Mohiuddin Syed 
Published: February 2025

Abstract

Background
Proliferative diabetic retinopathy (PDR) may lead to vision loss and blindness. The cost-effectiveness of various anti-vascular endothelial growth factor (anti-VEGF) drugs and panretinal photocoagulation (PRP) was assessed to supplement the NICE guideline for treating PDR.

Methods
A Markov model including eight levels of visual acuity (ranged between >85 and ≤25 letters) was developed to compare the cost-effectiveness of ranibizumab, aflibercept and bevacizumab with PRP (alone or in combination). Clinical inputs in the model were based on literature, while a published network meta-analysis (NMA) informed visual outcomes. Costs were estimated from a UK NHS perspective.

Results
Assuming initial treatment effects from the NMA continued to be applied for the remainder of lifetime, the probabilistic analysis resulted in bevacizumab plus PRP producing the highest net monetary benefit (NMB [95% CI]) of £221,374 [£203,941–£238,388] at £20,000 per quality-adjusted life-year. However, assuming initial treatment effects stabilised over time resulted in PRP alone producing the highest NMB of £223,416 [£209,318–£236,866]. Results were associated with large uncertainty due to wide confidence intervals around vision-based treatment effects of anti-VEGFs versus PRP, particularly for bevacizumab as data were drawn from trials with small sample size and high risk of bias. Using confidential prices for aflibercept and ranibizumab did not change the overall findings.

Conclusions
PRP is likely to be more cost-effective than anti-VEGFs for PDR. However, the results should be interpreted with caution given the scarcity of long-term visual outcomes with anti-VEGFs in this population. Further research on long-term visual outcomes may resolve these uncertainties.
Developing mRNA lipid nanoparticle vaccine effective for cryptococcosis in a murine model
Authors: Li Yeqi , Ambati Suresh , Meagher Richard B. , Lin Xiaorong 
Published: February 2025

Abstract

Cryptococcus neoformans is considered a critical fungal pathogen by the World Health Organization and developing a vaccine for cryptococcosis is a top priority. Here, we employed mRNAs encoding an antigen(s) packaged in lipid nanoparticles (LNPs) to develop vaccines for cryptococcosis. Remarkably, when coupled with capsule adjuvant, vaccination with CDA1-LNPs protected the vast majority of mice from the otherwise lethal cryptococcosis. These results support the promise of mRNA-LNP vaccines against fungal diseases.
A comprehensive spatio-cellular map of the human hypothalamus
Authors: Tadross John A. , Steuernagel Lukas , Dowsett Georgina K. C. , Kentistou Katherine A. , Lundh Sofia , Porniece Marta , Klemm Paul , Rainbow Kara , Hvid Henning , Kania Katarzyna , Polex-Wolf Joseph , Knudsen Lotte Bjerre , Pyke Charles , Perry John R. B. , Lam Brian Y. H. , Brüning Jens C. , Yeo Giles S. H. 
Published: February 2025

Abstract
The hypothalamus is a brain region that plays a key role in coordinating fundamental biological functions1. However, our understanding of the underlying cellular components and neurocircuitries have, until recently, emerged primarily from rodent studies2,3. Here we combine single-nucleus sequencing of 433,369 human hypothalamic cells with spatial transcriptomics, generating a comprehensive spatio-cellular transcriptional map of the hypothalamus, the ‘HYPOMAP’. Although conservation of neuronal cell types between humans and mice, as based on transcriptomic identity, is generally high, there are notable exceptions. Specifically, there are significant disparities in the identity of pro-opiomelanocortin neurons and in the expression levels of G-protein-coupled receptors between the two species that carry direct implications for currently approved obesity treatments. Out of the 452 hypothalamic cell types, we find that 291 neuronal clusters are significantly enriched for expression of body mass index (BMI) genome-wide association study genes. This enrichment is driven by 426 ‘effector’ genes. Rare deleterious variants in six of these (MC4R, PCSK1, POMC, CALCR, BSN and CORO1A) associate with BMI at population level, and CORO1A has not been linked previously to BMI. Thus, HYPOMAP provides a detailed atlas of the human hypothalamus in a spatial context and serves as an important resource to identify new druggable targets for treating a wide range of conditions, including reproductive, circadian and metabolic disorders.
Correlation of ferritin and glutathione peroxidase 4 (GPX4) level as a marker of ferroptosis process in endometrioma
Authors: Nulianti Rina , Bayuaji Hartanto , Ritonga Mulyanusa Amarullah , Djuwantono Tono , Tjahyadi Dian , Rachmawati Anita , Dwiningsih Sri Ratna , Nisa Aisyah Shofiatun , Adriansyah Putri Nadhira Adinda 
Published: February 2025

Abstract
Endometriosis is a chronic inflammatory disease characterized by the presence of endometrial-like tissues (glands and stroma) located outside the uterine cavity. The pathophysiology of this condition remains incompletely understood. Local bleeding and inflammation within endometriosis lesions, which occur in an environment rich in iron, reactive oxygen species (ROS), and free radicals, can disturb the balance of iron within the peritoneal cavity. This disruption can trigger oxidative injury and an inflammatory response, leading to ferroptosis, particularly in the endometrioma phenotype. This research utilized an observational analytical method with a cross-sectional design to examine the relationship between ferritin and GPx4 levels by assessing them simultaneously. The data collection occurred at Dr. Hasan Sadikin Hospital, Cibabat Hospital, Bandung Kiwari Hospital, and Limijati Women and Children Hospital Bandung. Observational analytic data were gathered between February and July 2023 from female patients diagnosed with endometrioma who underwent either laparoscopic or laparotomy surgery, either for therapeutic or diagnostic reasons. There were 58 patients who met the inclusion and exclusion criteria in this study. A significant correlation was observed between ferritin and glutathione peroxidase 4 (GPx4) levels with a correlation coefficient of -0.600 (p < 0.001). However, there was no significant correlation between both ferritin levels and the severity of endometriosis (based on Association of Gynecologic Laparoscopists staging). There was significant correlation between ferritin and glutathione peroxidase 4 (GPx4) levels.
Body image of men and women with congenital heart disease over a 15 years observational period
Authors: Geyer Siegfried , Dellas Claudia , Brähler Elmar , Beller Johannes 
Published: February 2025

Abstract
Most studies devoted to the psychological consequences of congenital heart disease (CHD) have dealt with consequences in terms of psychopathology. We wanted to consider two specific aspects of body image, “Rejecting body evaluation” and “Vital body dynamics”. We examined body image of CHD-patients as compared with the general population, the stability of body image of patients over time, and the relationship of body image with disease severity. The study combined a longitudinal (panel-) and a case-control design. The findings were based on a long-term study of CHD-patients with two surveys about 15 years apart with N = 244 who participated in both. The control group consisted of the same number of cases matched by age, gender and education drawn from a national survey designed to examine body image in the general population. More men than women were classified into the group with severe CHD. Body image differences between CHD-patients and controls were found only in men, but not in women, and they emerged primarily in terms of vitality. The two dimensions of body image turned out as moderately to strongly stable over time, relationships between disease severity and body image emerged only for perceived vitality. Contrary to expectation, effects of age and sex were largely absent. The body image of men turned out to be more affected by congenital heart disease than women. Body image is not stable, but it is changing with increasing age, and disease severity is affecting body image only in terms of the perception of physical performance.
Applying the layers of protection analysis (LOPA) method to high containment level biological facilities
Authors: Harsono Andrian , Waters Ryan , Tearle Jason , Harkess Graeme 
Published: February 2025

Abstract
The Layers of Protection Analysis (LOPA) method is a semi-quantitative risk assessment tool that is used to determine the ability of safeguards to protect against unplanned hazardous scenarios. One possible outcome of a LOPA is that existing and proposed safeguards are deemed sufficient to reduce the risk associated with the hazardous scenario to a level that can be deemed as acceptable. Alternatively, the LOPA may also show that the safeguards are insufficient and therefore additional Safety Instrumented Function(s) (SIF) would be required to reduce risk to an acceptable level. In the latter case, the LOPA method will inform the end user as to the reliability requirements of the safety function in question. The LOPA method has been used extensively in the process industries (e.g., oil and gas) as a useful tool to manage and understand risk and to demonstrate if the facility is ‘safe’ to operate, but much less so in the biosafety sector. This paper describes the LOPA method and provides some practical examples of how it may be applied in microbiological high Containment Level (CL) facilities.
Machine learning for classifying chronic kidney disease and predicting creatinine levels using at-home measurements
Authors: Metherall Brady , Berryman Anna K. , Brennan Georgia S. 
Published: February 2025

Abstract
Chronic kidney disease (CKD) is a global health concern with early detection playing a pivotal role in effective management. Machine learning models demonstrate promise in CKD detection, yet the impact on detection and classification using different sets of clinical features remains under-explored. In this study, we focus on CKD classification and creatinine prediction using three sets of features: at-home, monitoring, and laboratory. We employ artificial neural networks (ANNs) and random forests (RFs) on a dataset of 400 patients with 25 input features, which we divide into three feature sets. Using 10-fold cross-validation, we calculate metrics such as accuracy, true positive rate (TPR), true negative rate (TNR), and mean squared error. Our results reveal RF achieves superior accuracy (92.5%) in at-home CKD classification over ANNs (82.9%). ANNs achieve a higher TPR (92.0%), but a lower TNR (67.9%) compared with RFs (90.0% and 95.8%, respectively). For monitoring and laboratory features, both methods achieve accuracies exceeding 98%. The R2 score for creatinine regression is approximately 0.3 higher with laboratory features than at-home features. Feature importance analysis identifies the key clinical variables hemoglobin and blood urea, and key comorbidities hypertension and diabetes mellitus, in agreement with previous studies. Machine learning models, particularly RFs, exhibit promise in CKD diagnosis and highlight significant features in CKD detection. Moreover, such models may assist in screening a general population using at-home features—potentially increasing early detection of CKD, thus improving patient care and offering hope for a more effective approach to managing this prevalent health condition.
Associations of cachexia and frailty with amyotrophic lateral sclerosis
Authors: Peters Tracy L. , Qiu Weihong , Yang Haomin , Huang Wuqing , Hu Yizhen , Zou Zhangyu , Ye Weimin 
Published: February 2025

Abstract
In the present study, we investigated the associations of cachexia (loss of muscle, weight and fat) and frailty (loss of weight and muscle) status with the risk of developing amyotrophic lateral sclerosis, because these specific terms are rarely used in this research area. In this prospective study, we extracted cachexia and frailty status from the UK Biobank cohort to study the associations of these conditions (as determined via international classification of disease-10 codes) with amyotrophic lateral sclerosis. There was a greater risk of developing amyotrophic lateral sclerosis among individuals with cachexia and frailty status after adjusting for age, sex, income (pounds), body mass index, UK Biobank centers and smoking status. Among individuals with frailty status: a grip strength of < 21 kg, a slow walking speed, and exhaustion (more than half the days or nearly every day) increase the risk of developing amyotrophic lateral sclerosis. We believe that studying cachexia and frailty status can be used to help define and treat amyotrophic lateral sclerosis.
Drivers and mechanisms contributing to excess warming in Europe during recent decades
Authors: Dong Buwen , Sutton Rowan T. 
Published: February 2025

Abstract
Over the period 1979-2022, European surface air temperatures warmed around three times as fast as the global mean temperatures in both winter and summer. Here we define “excess” European warming as the difference between the rate of European regional warming and the rate of global warming and investigate the causes. Using a simple observation-based method, we estimate that around 40% ± 39% (in winter) and 29% ± 10% (in summer) of excess European warming is “dynamical” - attributable to changes in atmospheric circulation. We show that the rate of European warming simulated in CMIP6 models compares well with the observations, but only because these models warm too fast in the global mean; excess European warming is underestimated, particularly in winter. The CMIP6 models simulate well the magnitude of the thermodynamic component of excess European warming since 1979 in both winter and summer, they suggest only a weak dynamical contribution in the multi-model mean. The models suggest greenhouse gas-induced warming made the largest contribution to excess thermodynamic warming in winter, whereas changes in anthropogenic aerosols made the largest contribution in summer. They also imply a substantially reduced future rate of excess European warming in summer. However, the failure of current models to simulate observed circulation trends (either as a forced response or as a combination of forced response and internal variability) also implies large uncertainty in future rates of European warming.
Coordination between ESCRT function and Rab conversion during endosome maturation
Authors: Ott Daniel P , Desai Samit , Solinger Jachen A , Kaech Andres , Spang Anne 
Published: February 2025

Abstract
The endosomal pathway is essential for regulating cell signaling and cellular homeostasis. Rab5 positive early endosomes receive proteins from the plasma membrane. Dependent on a ubiquitin mark on the protein, they will be either recycled or sorted into intraluminal vesicles (ILVs) by endosomal sorting complex required for transport (ESCRT) proteins. During endosome maturation Rab5 is replaced by Rab7 on endosomes that are able to fuse with lysosomes to form endolysosomes. However, whether ESCRT-driven ILV formation and Rab5-to-Rab7 conversion are coordinated remains unknown. Here we show that loss of early ESCRTs led to enlarged Rab5 positive endosomes and prohibited Rab conversion. Reduction of ubiquitinated cargo alleviated this phenotype. Moreover, ubiquitinated proteins on the endosomal limiting membrane prevented the displacement of the Rab5 guanine nucleotide exchange factor (GEF) RABX-5 by the GEF for Rab7, SAND-1/CCZ-1. Overexpression of Rab7 could partially overcome this block, even in the absence of SAND-1 or CCZ1, suggesting the presence of a second Rab7 GEF. Our data reveal a hierarchy of events in which cargo corralling by ESCRTs is upstream of Rab conversion, suggesting that ESCRT-0 and ubiquitinated cargo could act as timers that determine the onset of Rab conversion.
LGS‐Net: A lightweight convolutional neural network based on global feature capture for spatial image steganalysis
Authors: Ma Yuanyuan , Wang Jian , Zhang Xinyu , Wang Guifang , Xin Xianwei , Zhang Qianqian 
Published: February 2025

AbstractThe purpose of image steganalysis is to detect whether the transmitted images in network communication contain secret messages. Current image steganalysis networks still have some problems such as inappropriate feature selection and easy overfitting. Therefore, this paper proposed a new spatial image steganalysis method based on convolutional neural networks. To extract richer features while reducing useless
parameters in the network, this paper introduced the Im SRM filtering kernel into the image preprocessing module. To extract effective steganography noise from images, this paper combined depthwise separable convolution and residual networks for the first time and introduces them into the steganography noise extraction module. In addition, to focus network attention on the image regions where steganography information exists, this paper integrated the coordinate attention mechanism. This module will make the network pay attention to the overall structure and local details of the image during network training, improving the network's recognition ability for steganography information. Finally, the extracted steganography features are classified through a classification module. This paper conducted a series of experiments on the BOSSBase 1.01 and BOWS2 datasets. The improvement in detection accuracy is between 1.2% and 18.2% compared to classic and recent steganalysis networks.