bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanistic Characterization of Cancer-associated Fibroblast Depletion via an Antibody–Drug Conjugate Targeting Fibroblast Activation Protein
Authors: Gallant Joseph P. , Hintz Hallie M. , Gunaratne Gihan S. , Breneman Matthew T. , Recchia Emma E. , West Jayden L. , Ott Kendahl L. , Heninger Erika , Jackson Abigail E. , Luo Natalie Y. , Rosenkrans Zachary T. , Hernandez Reinier , Zhao Shuang G. , Lang Joshua M. , Meimetis Labros , Kosoff David , LeBeau Aaron M. 
Published: May 2024

Abstract

Cancer-associated fibroblasts (CAF) are a prominent cell type within the tumor microenvironment (TME) where they are known to promote cancer cell growth and survival, angiogenesis, drug resistance, and immunosuppression. The transmembrane prolyl protease fibroblast activation protein (FAP) is expressed on the surface of highly protumorigenic CAFs found in the stroma of nearly every cancer of epithelial origin. The widespread expression of FAP has made it an attractive therapeutic target based on the underlying hypothesis that eliminating protumorigenic CAFs will disrupt the cross-talk between components of TME resulting in cancer cell death and immune infiltration. This hypothesis, however, has never been directly proven. To eliminate FAP-expressing CAFs, we developed an antibody–drug conjugate using our anti-FAP antibody, huB12, coupled to a monomethyl auristatin E (huB12-MMAE) payload. After determining that huB12 was an effective targeting vector, we found that huB12-MMAE potently eliminated FAP-expressing cells as monocultures in vitro and significantly prolonged survival in vivo using a xenograft engineered to overexpress FAP. We investigated the effects of selectively eliminating CAFs using a layered, open microfluidic cell coculture platform, known as the Stacks. Analysis of mRNA and protein expression found that treatment with huB12-MMAE resulted in the increased secretion of the proinflammatory cytokines IL6 and IL8 by CAFs and an associated increase in expression of proinflammatory genes in cancer cells. We also detected increased secretion of CSF1, a cytokine involved in myeloid recruitment and differentiation. Our findings suggest that the mechanism of FAP-targeted therapies is through effects on the immune microenvironment and antitumor immune response.

Significance:
The direct elimination of FAP-expressing CAFs disrupts the cross-talk with cancer cells leading to a proinflammatory response and alterations in the immune microenvironment and antitumor immune response.
Likeness across Nature
Authors: Cooley Mackenzie 
Published: May 2024

Abstract
Over the course of a long career, Hieronymus Fabricius of Aquapendente sought to train students and readers to think across nature. This article suggests that we read his program as inculcating an “anatomical eye”: a visual language of the body’s logic and nature’s intention that encoded knowledge, which expert anatomists derived from touch and sight combined. Fabricius both taught and learned haptically, observing organs’ divisions through variations in texture and measuring the differences in reproductive anatomy across animals with his fingers. Through dissections of sheep, cattle, horses, sharks, guinea pigs, dogs, and humans, he gathered details about how nature had produced both startling likenesses and particularities across the animal kingdom. While artists sometimes struggled to capture his experience, Fabricius’s longstanding commitment to working with them revealed that, whatever the challenges, the potential for expanding the “anatomical eye,” and the reputation that came with it, was worth the risk.
Enhanced Mid-to-Late Summer Precipitation over Midlatitude East Asia under Global Warming
Authors: Wang Chuan-Yang , Zheng Xiao-Tong , Song Fengfei 
Published: May 2024

Abstract
East Asian summer monsoon precipitation is projected to increase under greenhouse warming with strong intraseasonal variation. Using a 35-member CESM Large Ensemble and 30 CMIP6 models, this study reveals that in July and August, maximum rainfall changes in East Asia take place in the midlatitudes, influencing regions encompassing North and Northeast China, the Korean Peninsula, and Japan. The intensified precipitation is attributed to the combined effect of the thermodynamic and dynamic components. The former stems from the enriched low-level moisture, which peaks in continental East Asia in July and August, under global warming. The dynamic effect is due to the enhanced upward motion, associated with the enhanced southerlies throughout the troposphere over midlatitude East Asia. The southerlies also act to intensify the low-level monsoonal circulation, strengthening moisture transport from the tropical ocean to the midlatitudes. In addition to the mean-state changes, the precipitation interannual variability in this region also intensifies, partly due to the enhanced low-level moisture and partly associated with enhanced large-scale circulation anomalies, such as the northwestern Pacific anticyclone. The enhanced background precipitation, along with the intensified interannual variability, may lead to more rainy summers in a warmer climate, with instances where historically extreme precipitation events become more frequent, posing challenges for water resource management and agriculture in the region.
Compound Flooding Potential from the Joint Occurrence of Precipitation and Storm Surge in the Qiantang Estuary, China
Authors: Wu Yanjuan , Haigh Ivan D. , Gao Chao , Jenkins Luke J. , Green Joshua , Jane Robert , Xu Yu , Hu Hengzhi , Wu Naicheng 
Published: May 2024

Abstract
In coastal regions, compound flooding, driven by multiple flood hazard sources, can cause greater damage than when the flood drivers occur in isolation. This study focuses on compound flooding from extreme precipitation and storm surge in China’s Qiantang Estuary. We quantify the potential of compound flooding by measuring bivariate joint statistical dependence and joint return period (JRP). We find a significant positive dependence between the two flood drivers considered, as indicated by Kendall’s rank correlation coefficients. Compound events occur frequently, with an average of 2.65 events per year from 1979 to 2018, highlighting the significant concern of compound flooding for this estuary. Using a copula model, we demonstrate that considering the dependence between the two flood drivers shortens the JRP of compound flooding compared to the JRP assuming total independence. For a 1-in-10-yr precipitation event and 1-in-10-yr storm surge event, the JRP is 1 in 100 years when assuming total independence. However, it decreases to 1 in 32.44 years when considering their dependence. Ignoring the dependence between flood drivers can lead to an increase in the JRP of compound events, resulting in an underestimation of the overall flood risk. Our analysis reveals a strong link between the weather patterns creating compound events and extreme storm surge only events with tropical cyclone activity. Additionally, the extreme precipitation only events were found to be connected with the frontal system of the East Asian summer monsoon. This study highlights the importance of considering the dependence between multiple flood drivers associated with certain types of the same weather systems when assessing the flood risk in coastal regions.
Structure and Maintenance of a Quasi-Linear Mesoscale Convective System That Caused Torrential Rain in Southern Kyushu, Japan, on 11 July 2021
Authors: Mashiko Wataru 
Published: May 2024

Abstract
A quasi-linear mesoscale convective system that remained nearly stationary (hereafter referred to as a stationary QLCS) for almost 8 h in southern Kyushu, Japan, caused torrential rainfall exceeding 350 mm on 11 July 2021. The stationary QLCS consisted of several rainbands organized by back-building convection. As the cold pool intensified, the system attained a more widespread structure, leaning on the upshear side. To elucidate the mechanism responsible for the upshear tilt, numerical simulations with 250-m horizontal grid spacing were conducted, including sensitivity experiments in which the evaporative cooling rates from rain were reduced to modify the cold pool intensity. Results show that the cold pool is critical to the organization of the QLCS, and the structure normal to it is mainly governed by the balance between the low-level shear magnitude and cold pool intensity, supporting the application of so-called Rotunno–Klemp–Weisman (RKW) theory to this event. The cause of the weak updraft that accompanies the leaning system over the strong cold pool was also investigated, analyzing the trajectories, vertical momentum equation, and pressure perturbation field using the anelastic equation. It is revealed that the updraft travels a longer distance through the tilted system experiencing more mixing with the ambient air, which results in less thermal buoyancy. In addition, the updraft is decelerated by the downward perturbation gradient force owing to the vertical buoyancy gradient around the sloping surface of the cold pool and the dynamical effect caused by the baroclinicity-associated strong horizontal vorticity around the cold pool leading edge.
Value of the HOTAIR expression assay in predicting therapy target in hepatocellular carcinoma: A meta-analysis and bioinformatics analysis
Authors: Wen Ping , Qi Xiyu , Zheng Ruzhen 
Published: May 2024

Background Several studies show that the long non-coding RNA HOX transcript antisense RNA (HOTAIR) was upregulated in human cancer, which was associated with several clinical features and may have the potential to be prognostic markers. However, the significance of HOTAIR in hepatocellular carcinoma remains unclear. We performed a meta-analysis and bioanalysis to further investigate the association between HOTAIR and hepatocellular carcinoma. Methods Eligible literature was systematically retrieved from PubMed, Embase, and Web of Science databases. The pooled hazard ratios with 95% confidence intervals were used to evaluate to the effect. Raw data on HOTAIR expression were obtained from The Cancer Genome Atlas data portals. All bioinformatics analyses were performed using R software (version 4.3.1). Results We identified eight studies in this meta-analysis with a total of 399 patients. High-level HOTAIR expression was found to be significantly related to advanced tumor node metastasis stage, distant metastasis, poor tumor differentiation, and patients with hepatitis. Correspondingly, HOTAIR was also associated with poor overall survival and relapse-free survival. Subsequently, in bioanalysis, HOTAIR expression was higher in hepatocellular carcinoma as well as poor overall survival. High HOTAIR expression was strongly correlated with tumor node metastasis stage. Kyoto Encyclopedia of Genes and Genomes analysis revealed that the differentially expressed genes related to HOTAIR may be involved in the cancer-associated signaling pathway. Conclusion HOTAIR may be a potential biomarker for HCC prediction and is expected to become a new choice for clinical HCC prediction..
The Role of the Tissue Perfusion Index in Predicting Disease Severity and Prognosis in Patients with Severe and Critical COVID-19
Authors: Lin Wan-Ting , Zhang Yan-Jie , Yan Ming-Kun , Cai Xiao-Tian , Cai Xin-Er , Xu Jingyuan 
Published: May 2024

Objectives The study investigated whether percutaneous partial pressure of oxygen (PtcO2), percutaneous partial pressure of carbon dioxide (PtcCO2), and the derived tissue perfusion index (TPI) can predict the severity and short-term outcomes of severe and critical COVID-19. Design Prospective observational study conducted from January 1, 2023 to February 10, 2023. Setting A teaching hospital specializing in tertiary care in Nanjing City, Jiangsu Province, China. Participants Adults (≥18 years) with severe and critical COVID-19. Interventions Not applicable. Main outcome measures The general information and vital signs of the patients were collected. The PtcO2 and PtcCO2 were monitored in the left dorsal volar. The ratio of TPI was defined as the ratio of PtcO2/fraction of inspired oxygen (FiO2) to PtcCO2. Mortality at 28 was recorded. The ability of the TPI to assess disease severity and predict prognosis was determined. Endpoint Severity of the disease on the enrollment and mortality at 28. Results A total of 71 patients with severe and critical COVID-19, including 40 severe and 31 critical cases, according to the COVID-19 treatment guidelines published by WHO, were recruited. Their median age was 70 years, with 56 (79%) males. The median SpO2/FiO2, PtcO2, PtcCO2, PtcO2/ FiO2, and TPI values were 237, 61, 42, 143, and 3.6 mm Hg, respectively. Compared with those for severe COVID-19, the TPI, PtcO2/ FiO2, SpO2/FiO2, and PtcO2 were significantly lower in critical COVID-19, while the PtcCO2 was significantly higher. After 28 days, 26 (37%) patients had died. TPI values < 3.5 were correlated with more severe disease status (AUC 0.914; 95% CI: 0.847-0.981, P < 0.001), and TPI < 3.3 was associated with poor outcomes (AUC 0.937; 95% CI 0.880-0.994, P < 0.001). Conclusions The tissue perfusion index (TPI), PtcCO2, and PtcO2/ FiO2 can predict the severity and outcome of severe and critical COVID-19.
Psychiatric Mental Health Nurses’ Perceptions and Experiences of Inpatient Mental Health Care Safety Culture in Saudi Arabia
Authors: Alyousef Seham Mansour , Alhamidi Sami Abdulrahman 
Published: May 2024

Background: Although patient safety culture is gaining attention globally, more studies are needed to investigate its relevance to the nursing care of mental health (MH) patients. Aims: This study aimed to illustrate the perceptions and experiences of nurses who work in inpatient mental health care (IMHC) concerning the patient safety practices that are employed to avert safety hazards encountered during the provision of care in IMHC settings. Methods: Eighteen postgraduate students working as MH nurses in nonprofit hospitals comprised the study sample. The participants had a minimum of 2 years’ nursing experience in IMHC settings. Each participant was interviewed individually using a guided interview technique. The inductive data underwent thematic analysis. Results: Patient protection and a safety perspective were the overarching themes that emerged from the data. Three principal themes and 9 subthemes were illuminated: (a) patient care safety knowledge and background, (b) improving MH care, and (c) development of MH nursing care. Conclusions: The findings of this investigation may assist in providing guidance for the further research into and development of a patient safety culture appropriate for IMHC nursing practice, including increased structured educational experiences, judicious risk assessment, assignment of staff to include a mixture of skills and experience levels during assignments, use of standardized handoff procedures, engagement with multidisciplinary care providers, blame-free reflective information sharing and mentoring, and attention to the built environment with consideration of patient and staff safety needs.
Environmental Predictors of Undernutrition Among Under-5 Children at Dabat District Health Facilities, Northwest Ethiopia, 2023
Authors: Melese Mihret , Esubalew Dereje , Malede Asmamaw , Birhan Tsegaye Adane , Azanaw Jember 
Published: May 2024

Background: In Ethiopia, undernutrition remains a significant public health concern throughout the year due to persistent household food insecurit. The intensifying conflict in the Dabat district, involving the Ethiopian government and the Tigray Liberation Front, has increased the threat of undernutrition among under-5 children. The cessation of humanitarian aid has worsened food insecurity, increasing the vulnerability of the children in the region. However,there was no data showing the prevalence and environmental pridictors of undernutrition in the Dabat district, northwestern Ethiopia. Therefore, the objective of this study was to determine the prevalence of undernutrition and identify environmental pridictors in this study setting. Methods: This institutional-based cross-sectional study was conducted from January to March 2023. A total of 400 under-5 children were included in this study using systematic random sampling techniques with a 100% response rate. The study included all under-5 children who visited healthcare facilities during the data collection period. However, it excluded children under-5 who had physical deformities, were critically ill, or had congenital abnormalities or known chronic diseases such as HIV/AIDS, tuberculosis, or chronic heart diseases. Binary logistic regression was used to determine environmental predictors of undernutrition, with statistical significance at a P-value of ⩽.05. Results: The overall prevalence of undernutrition was found to be 12% (95% CI: 8.72-21.5). Among those affected, 32.8% (95% CI: 21.5-39.8) were stunted, 37.9% (95% CI: 28.8-47.50) were underweight, and 29.3% (95% CI: 21.3-29.7) were wasted. The environmental predictors of undernutrition were latrine use, recent diarrhea episodes, mothers’ occupation and place of residence, water treatment before consumption, water sources and storage, water extraction methods, and mothers’ handwashing habits. Conclusions and recommendations: The study found a higher prevalence of undernutrition among under-5 children compared to the 2019 Ethiopia Mini Demographic and Health Survey. This study recommended raising awareness about establishing private toilets, promoting water treatment, proper latrine use, and handwashing practices. Training on personal hygiene and economic support for households should also be provided. Healthcare providers should offer quality health services for under-5 children. Further research is needed to explore specific nutrient deficiencies using laboratory methods.
Malignancy pattern analysis of breast ultrasound images using clinical features and a graph convolutional network
Authors: Montaha Sidratul , Azam Sami , Bhuiyan Md. Rahad Islam , Chowa Sadia Sultana , Mukta Md. Saddam Hossain , Jonkman Mirjam 
Published: May 2024

Objective Early diagnosis of breast cancer can lead to effective treatment, possibly increase long-term survival rates, and improve quality of life. The objective of this study is to present an automated analysis and classification system for breast cancer using clinical markers such as tumor shape, orientation, margin, and surrounding tissue. The novelty and uniqueness of the study lie in the approach of considering medical features based on the diagnosis of radiologists. Methods Using clinical markers, a graph is generated where each feature is represented by a node, and the connection between them is represented by an edge which is derived through Pearson's correlation method. A graph convolutional network (GCN) model is proposed to classify breast tumors into benign and malignant, using the graph data. Several statistical tests are performed to assess the importance of the proposed features. The performance of the proposed GCN model is improved by experimenting with different layer configurations and hyper-parameter settings. Results Results show that the proposed model has a 98.73% test accuracy. The performance of the model is compared with a graph attention network, a one-dimensional convolutional neural network, and five transfer learning models, ten machine learning models, and three ensemble learning models. The performance of the model was further assessed with three supplementary breast cancer ultrasound image datasets, where the accuracies are 91.03%, 94.37%, and 89.62% for Dataset A, Dataset B, and Dataset C (combining Dataset A and Dataset B) respectively. Overfitting issues are assessed through k-fold cross-validation. Conclusion Several variants are utilized to present a more rigorous and fair evaluation of our work, especially the importance of extracting clinically relevant features. Moreover, a GCN model using graph data can be a promising solution for an automated feature-based breast image classification system.
Low-intensity repetitive transcranial magnetic stimulation is safe and well tolerated by people living with MS – outcomes of the phase I randomised controlled trial (TAURUS)
Authors: Nguyen Phuong Tram , Zarghami Amin , Makowiecki Kalina , Stevens Natasha , Ezegbe Chigozie , Kyle Kain , Wang Chenyu , Ly Linda , De La Rue Katie , Hinder Mark R , Johnson Lewis , Rodger Jennifer , Cooper Samantha , Cullen Carlie L , Barnett Michael , Young Kaylene M , Taylor Bruce V 
Published: May 2024

Background Low-intensity repetitive transcranial magnetic stimulation (rTMS), delivered as a daily intermittent theta burst stimulation (iTBS) for four consecutive weeks, increased the number of new oligodendrocytes in the adult mouse brain. Therefore, rTMS holds potential as a remyelinating intervention for people with multiple sclerosis (MS). Objective Primarily to determine the safety and tolerability of our rTMS protocol in people with MS. Secondary objectives include feasibility, blinding and an exploration of changes in magnetic resonance imaging (MRI) metrics, patient-reported outcome measures (PROMs) and cognitive or motor performance. Methods A randomised (2:1), placebo controlled, single blind, parallel group, phase 1 trial of 20 rTMS sessions (600 iTBS pulses per hemisphere; 25% maximum stimulator output), delivered over 4–5 weeks. Twenty participants were randomly assigned to ‘sham’ ( n = 7) or active rTMS ( n = 13), with the coil positioned at 90° or 0°, respectively. Results Five adverse events (AEs) including one serious AE reported. None were related to treatment. Protocol compliance was high (85%) and blinding successful. Within participant MRI metrics, PROMs and cognitive or motor performance were unchanged over time. Conclusion Twenty sessions of rTMS is safe and well tolerated in a small group of people with MS. The study protocol and procedures are feasible. Improvement of sham is warranted before further investigating safety and efficacy.
Biological and clinical determinants shaping heterogeneity in mantle cell lymphoma
Authors: López Cristina , Silkenstedt Elisabeth , Dreyling Martin , Beà Sílvia 
Published: May 2024

Abstract
Mantle cell lymphoma (MCL) is an uncommon mature B-cell lymphoma that presents a clinical spectrum ranging from indolent to aggressive disease, with challenges in disease management and prognostication. MCL is characterized by significant genomic instability, affecting various cellular processes, including cell cycle regulation, cell survival, DNA damage response and telomere maintenance, NOTCH and NF-κB/ B-cell receptor pathways, and chromatin modification. Recent molecular and next-generation sequencing studies unveiled a broad genetic diversity among the 2 molecular subsets, conventional MCL (cMCL) and leukemic nonnodal MCL (nnMCL), which may partially explain their clinical heterogeneity. Some asymptomatic and genetically stable nnMCL not requiring treatment at diagnosis may eventually progress clinically. Overall, the high proliferation of tumor cells, blastoid morphology, TP53 and/or CDKN2A/B inactivation, and high genetic complexity influence treatment outcome in cases treated with standard regimens. Emerging targeted and immunotherapeutic strategies are promising for refractory or relapsed cases and a few genetic and nongenetic determinants of refractoriness have been reported. This review summarizes the recent advances in MCL biology, focusing on molecular insights, prognostic markers, and novel therapeutic approaches.