bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preventing 5-fluorouracil-induced ischemic events in very high-risk cardiac patients: A retrospective cohort analysis (SQCCCRC protocol).
Authors: Basuoni Ahmad , Ghoche Ahmad , Abu Omar Rami , d A Waleed , Al-Moundhri Mansour 
Published: July 2024

e24112 Background: 5-Fluorouracil (5-FU), a potent chemotherapy agent for various cancers, is linked to cardiotoxicity, particularly in patients with pre-existing ischemic heart disease. The incidence varies, necessitating effective preventive strategies. Among the several mechanisms responsible for 5-FU-induced myocardial ischemia are coronary vasospasm and endothelial injury. Therefore, prevention of ischemic events in very high-risk patients by controlling modifiable cardiac risk factors and good medical treatment including vasodilators are a potential strategy in preventing 5-FU ischemic events. Methods: To assess the effectiveness and safety of a protocol involving Amlodipine and Isosorbide dinitrate in preventing 5-FU-induced ischemic events in very high-risk cardiac patients with documented ischemic heart disease. Nineteen patients underwent 252 cycles of 5-FU chemotherapy, with 12 patients (181 cycles) following the pre-defined protocol (5-FU Protocol Group) and 7 patients (71 cycles) not adhering (Missed 5-FU Protocol Group). The primary outcome measure was the prevention of 5-FU-induced ischemic events, evidenced by the absence of chest pain, elevated Troponin levels, or ECG changes during 5-FU infusion. Results: The 5-FU Protocol Group demonstrated significant reductions in ischemic events, chest pain with p-values of 0.009 for both outcomes. Additionally, the occurrence of ECG changes post-5FU and an increase in Troponin levels was significantly lower in the 5-FU Protocol Group, with p-values of 0.036 for both parameters. Although not statistically significant, there was a lower 5FU-related mortality rate in the 5-FU Protocol Group compared to the missed 5-FU Protocol Group (0% vs. 14.3%, p = 0.37). The incidence of cancer-related mortality did not exhibit a statistically significant difference between the two groups. To evaluate this, we specifically examined and compared the occurrence of ischemic events in both the 5-FU Protocol Group and the Missed 5-FU Protocol Group. The comparison was conducted using the Fisher exact test. Conclusions: The use of vasodilators may be effective in preventing 5-Fluorouracil-Induced ischemic events in very high-risk cardiac patients with documented coronary artery disease. This approach may help reduce the risk of cardiac events and improve the safety of chemotherapy in this vulnerable patient population. Monitoring cardiotoxicity with maximum tolerated medical treatment and dedicated hospital protocols may be a good prophylaxis approach. Further studies are needed to confirm the safety and efficacy of this approach in a larger patient population, and to assess its impact on long-term cardiac outcomes.
Integrated analysis of single-cell data on role of NKG7high CD8+ Teff cells in driving immune-related adverse events.
Authors: Zhang Minghui , Wen Ti , Qu Xiujuan 
Published: July 2024

e24114 Background: Immune-related adverse events (irAEs) frequently occur during immunotherapy and can impact various organ systems, which dampen the clinical outcomes of immune checkpoint inhibitors (ICIs). However, the precise immune hallmarks associated with irAEs remain further explored. Methods: We collected public (Bukhari et al., Zhu et al., Su et al., and Ma et al.) and our own scRNA-seq data across patients with different irAE types or without irAEs. By comparing T cell compositions between irAE and no-irAE patients, the subcluster correlated with the occurrence of irAE was identified. Subsequently, the integrated analyses were performed to explore its mechanisms in driving irAEs in both peripheral blood and local tissues. Results: Compared to no-irAE patients, a subcluster of effector T (Teff) cells was observed to increase notably in the peripheral blood of irAE patients during immunotherapy. This specific subcluster, named "NKG7high CD8+ Teff cells," was characterized by the significant expression of effector genes such as GZMH, CCL5, and especially NKG7. In contrast to other CD8+ T cells, the NKG7high CD8+ Teff cells exhibited stronger cytotoxicity functions, increased exosome secretion, and enhanced MIF-CD74 interaction with monocytes, which suggests the mechanistic link between its increased infiltration and the development of irAEs. Further investigation showed these characteristics were more remarkable in NKG7high CD8+ Teff from irAE patients than no-irAE patients. Subsequently, the increase of NKG7high CD8+ Teff during immunotherapy was validated in our own scRNA from immune thyroiditis patients, which was not observed in no-irAE patients. Across various irAE types, NKG7high CD8+ Teff subsets, along with their NKG7 expression, demonstrated heightened infiltration and expression in immune-related arthritis and myocarditis samples. After investigating the role of NKG7high CD8+ Teff in peripheral blood, we focused on its distribution and roles in local irAE tissue. NKG7high CD8+ Teff cells accumulated in immune-related thyroiditis tissues, and recruited macrophages through the IFNG and CSF1 signaling pathways, thereby inducing an immune overreaction. Meanwhile, in immune-related myocarditis mice heart tissues, NKG7high CD8+ Teff cells could interact with macrophages via the SPP1 signaling pathway and cause endothelial cell damage through the FASL-FAS pathway. Conclusions: This comprehensive study revealed the intricate mechanisms of NKG7high CD8+ Teff in inducing irAEs, providing valuable insights into their roles and potential implications in irAE treatment.
Role of celecoxib in reducing cognitive impairment in patients receiving definitive chemoradiation for head and neck carcinoma: A phase II randomized placebo controlled trial (CELCI-HN study).
Authors: Sharma Aparna , SHARMA ATUL , Thakar Alok , Bhasker Suman , Sikka Kapil , Singh Amit Chirom , Kumar Rajeev , Pramanik Raja , Patil Vaibhav , kumar akash , Kataria Babita , Singhal Abhinav , Panda Smriti , Sharma Aman , Izzuddeen Yousra , R Chethan 
Published: July 2024

TPS12150 Background: Head and neck squamous cell carcinoma (HNSCC) is common in the Indian subcontinent and majority (65%) patients present in an advanced stage. Chemotherapy related cognitive impairment (CRCI) is a poorly defined and underestimated phenomenon in the HNSCC population. Through this study, we are attempting to establish evidence of activity of agents targeting neuro-inflammation in reducing or halting cognitive decline associated with definitive chemoradiotherapy for head and neck malignancies without adding to treatment-associated toxicity. This study can potentially aid in developing a cost effective approach with a readily available and cheap agent like celecoxib in improving the quality of life in this cohort of patients. Methods: This is a single center, double blinded placebo controlled phase 2 randomized trial. We intend to randomize 92 non metastatic HNSCC patients registered at a large tertiary cancer center of North India {Department of Medical Oncology (Head and Neck Cancer Clinic, All India Institute of Medical Sciences-National Cancer Institute, India)} planned for definitive chemoradiation (CTRT) with or without induction chemotherapy. Patients in the experimental arm will receive celecoxib 100 mg or matched placebo tablet orally twice a day starting with day 1 of initiation of definitive chemoradiotherapy/induction chemotherapy for a duration of 6 months or until unacceptable toxicity. Our primary objective is to determine the activity of celecoxib versus placebo in reducing cognitive decline in patients undergoing definitive CTRT with or without induction chemotherapy in HNSCC through patient reported outcome tools (FACT cog questionnaire). Secondary objectives include assessment of adverse event profile (measured using CTCAE v5.0), objective assessment of neurocognitive decline using neuropsychological battery of tests, to identify predictors of cognitive decline on the basis of site of malignancy, radiation dose to the base of skull and brainstem, age, comorbidities and educational status. Tertiary objective include evaluation of inflammatory biomarkers e.g serum COX-2, serum Interleukin and tumor necrosis factors-alpha levels at the end of therapy and on follow up. Clinical trial information: CTRI/2022/09/045579.
Improving Prediction of Survival and Progression in Metastatic Non–Small Cell Lung Cancer After Immunotherapy Through Machine Learning of Circulating Tumor DNA
Authors: Ding Haolun , Xu Xu Steven , Yang Yaning , Yuan Min 
Published: July 2024

PURPOSE To use modern machine learning approaches to enhance and automate the feature extraction from the longitudinal circulating tumor DNA (ctDNA) data and to improve the prediction of survival and disease progression, risk stratification, and treatment strategies for patients with 1L non–small cell lung cancer (NSCLC). MATERIALS AND METHODS Using IMpower150 trial data on patients with untreated metastatic NSCLC treated with atezolizumab and chemotherapies, we developed a machine learning algorithm to extract predictive features from ctDNA kinetics, improving survival and progression prediction. We analyzed kinetic data from 17 ctDNA summary markers, including cell-free DNA concentration, allele frequency, tumor molecules in plasma, and mutation counts. RESULTS Three hundred and ninety-eight patients with ctDNA data (206 in training and 192 in validation) were analyzed. Our models outperformed existing workflow using conventional temporal ctDNA features, raising overall survival (OS) concordance index to 0.72 and 0.71 from 0.67 and 0.63 for C3D1 and C4D1, respectively, and substantially improving progression-free survival (PFS) to approximately 0.65 from the previous 0.54-0.58, a 12%-20% increase. Additionally, they enhanced risk stratification for patients with NSCLC, achieving clear OS and PFS separation. Distinct patterns of ctDNA kinetic characteristics (eg, baseline ctDNA markers, depth of ctDNA responses, and timing of ctDNA clearance, etc) were revealed across the risk groups. Rapid and complete ctDNA clearance appears essential for long-term clinical benefit. CONCLUSION Our machine learning approach offers a novel tool for analyzing ctDNA kinetics, extracting critical features from longitudinal data, improving our understanding of the link between ctDNA kinetics and progression/mortality risks, and optimizing personalized immunotherapies for 1L NSCLC.
Extracting work from two gravitational cat states
Authors: Hadipour Maryam , Haseli Soroush 
Published: July 2024

Abstract
Gravitational cat states in the context of gravity are superpositions of quantum states that exhibit macroscopically distinct gravitational fields. These states represent a unique blend of quantum mechanics and general relativity, providing insights into the behavior of quantum systems under gravitational influences. This study investigates the impact of thermal environments on the extractable work from gravitational cat states, which are quantum superpositions of distinct gravitational configurations. It aims to offer a comprehensive analysis of how temperature and gravitational interactions between states with masses m influence work extraction. The findings indicate that both an increase in temperature and the interactions between states reduce the amount of work that can be extracted from gravitational cat states, highlighting the delicate balance between thermal and gravitational effects in quantum systems.
Accelerated hermaphrodite maturation on male pheromones suggests a general principle of coordination between larval behavior and development
Authors: Faerberg Denis F. , Aprison Erin Z. , Ruvinsky Ilya 
Published: July 2024

ABSTRACT
Environment in general and social signals in particular could alter development. In Caenorhabditis elegans, male pheromones hasten development of hermaphrodite larvae. We show that this involves acceleration of growth and both somatic and germline development during the last larval stage (L4). Larvae exposed to male pheromones spend more time in L3 and less in the quiescent period between L3 and L4. This behavioral alteration improves provision in early L4, likely allowing for faster development. Larvae must be exposed to male pheromones in late L3 for behavioral and developmental effects to occur. Latter portions of other larval stages also contain periods of heightened sensitivity to environmental signals. Behavior during the early part of the larval stages is biased toward exploration, whereas later the emphasis shifts to food consumption. We argue that this organization allows assessment of the environment to identify the most suitable patch of resources, followed by acquisition of sufficient nutrition and salient information for the developmental events in the next larval stage. Evidence from other species indicates that such coordination of behavior and development may be a general feature of larval development.
CCL2 signaling promotes skeletal muscle wasting in non-tumor and breast tumor models
Authors: Alissa Nadia , Fang Wei Bin , Medrano Marcela , Bergeron Nick , Kozai Yuuka , Hu Qingting , Redding Chloe , Thyfault John , Hamilton-Reeves Jill , Berkland Cory , Cheng Nikki 
Published: July 2024

ABSTRACT
Despite advancements in treatment, approximately 25% of patients with breast cancer experience long-term skeletal muscle wasting (SMW), which limits mobility, reduces drug tolerance and adversely impacts survival. By understanding the underlying molecular mechanisms of SMW, we may be able to develop new strategies to alleviate this condition and improve the lives of patients with breast cancer. Chemokines are small soluble factors that regulate homing of immune cells to tissues during inflammation. In breast cancers, overexpression of C-C chemokine ligand 2 (CCL2) correlates with unfavorable prognosis. Elevated levels of CCL2 in peripheral blood indicate possible systemic effects of this chemokine in patients with breast cancer. Here, we investigated the role of CCL2 signaling on SMW in tumor and non-tumor contexts. In vitro, increasing concentrations of CCL2 inhibited myoblast and myotube function through C-C chemokine receptor 2 (CCR2)-dependent mechanisms involving JNK, SMAD3 and AMPK signaling. In healthy mice, delivery of recombinant CCL2 protein promoted SMW in a dose-dependent manner. In vivo knockdown of breast tumor-derived CCL2 partially protected against SMW. Overall, chronic, upregulated CCL2–CCR2 signaling positively regulates SMW, with implications for therapeutic targeting.
The role of the International Society for Stem Cell Research (ISSCR) guidelines in disease modeling
Authors: Juguilon Cody , Wu Joseph C. 
Published: July 2024

ABSTRACT
Human stem cell-based modeling systems are valuable tools that can greatly improve the clinical translation of basic research. Importantly, the successful application of human stem cell-based models to biomedical research depends on the widespread adoption of ethical principles and practical standards. To achieve this outcome, the International Society for Stem Cell Research (ISSCR) provides a comprehensive set of recommendations that aim to promote the ethical usage of human stem cells and to ensure rigor and reproducibility within the field. Understanding and implementing these recommendations should be a top priority for investigators around the world.
Short transmembrane domains target type II proteins to the Golgi apparatus and type I proteins to the endoplasmic reticulum
Authors: Bian Claudie , Marchetti Anna , Dias Marco , Perrin Jackie , Cosson Pierre 
Published: July 2024

ABSTRACT
Transmembrane domains (TMDs) contain information targeting membrane proteins to various compartments of the secretory pathway. In previous studies, short or hydrophilic TMDs have been shown to target membrane proteins either to the endoplasmic reticulum (ER) or to the Golgi apparatus. However, the basis for differential sorting to the ER and to the Golgi apparatus remained unclear. To clarify this point, we quantitatively analyzed the intracellular targeting of a collection of proteins exhibiting a single TMD. Our results reveal that membrane topology is a major targeting element in the early secretory pathway: type I proteins with a short TMD are targeted to the ER, and type II proteins to the Golgi apparatus. A combination of three features accounts for the sorting of simple membrane proteins in the secretory pathway: membrane topology, length and hydrophilicity of the TMD, and size of the cytosolic domain. By clarifying the rules governing sorting to the ER and to the Golgi apparatus, our study could revive the search for sorting mechanisms in the early secretory pathway.
Increasing abdominal circumference in children – does it require diagnosis?
Authors: Miazga Małgorzata , Ostojska Magdalena , Stręk Wojciech , Maślana Marianna , Bogoń Aleksandra , Woźniak Magdalena Maria 
Published: July 2024

Introduction and purpose: Wilms tumor, also known as nephroblastoma, is the most prevalent malignant tumor of the kidney in the pediatric population. 90% of them are diagnosed in children before the age of 6. This tumor is more common in girls, and usually occurs unilaterally. The purpose of the study is to analyse and present the incidence of the patients with Wilms tumor in University Children’s Hospital in Lublin in comparison to other studies published on PubMed.
Material and methods: The study included 34 patients with the Wilms tumor in the past medical history. They were selected among patients who had a computed tomography (CT) scan in the Department of Pediatric Radiology between November 2012 and October 2021.
Results: The average diagnostic age of Wilms tumor patients was 3 years and 9 months. The unilateral occurrence of the tumor was more common, also, the presence of a tumor in the left kidney was more frequent than in the right one. Metastases were mainly located in the lungs and liver. The less common sites of metastasis were pleural recesses and paraaortic lymph nodes. Treatment was mostly based on nephrectomy and chemotherapy, and less frequently, on radiotherapy. In the majority of patients, treatment resulted in regression of cancer lesions. Only a few recurrences of the disease were reported.
Conclusions: Successful treatment protocols for Wilms tumor (pre-operative chemotherapy and surgery) ensure a high survival rate. It is important to monitor the patient after treatment due to the risk of recurrence. During diagnostics, chest and abdominal CT should be considered because of the high incidence rate of lung and liver metastases.
Application of Geographic Information System (GIS) Technology to Formulate Unused Spring Water Optimization Strategy
Authors: Lisan Ahmad Rifan Khoirul , Murdiyanto Eko , Harsana Minta 
Published: July 2024

Background: This article presents the findings of a comprehensive community empowerment program that focused on the application of Geographic Information System (GIS) technology for the optimization strategy formulation of unused spring water.
Contribution: The contribution of this program address the challenge for better utilization of unused spring water and promote sustainable water management practices.
Method: The study employed GIS technology to identify and map unused springs, followed by hydrological analysis and water quality assessment to inform the development of optimization strategies.
Results: This program suggested infrastructure development, water conservation measures, and distribution network design to enhance water availability.

Conclusion: The findings show that GIS approach is suitable for further applications in other Indonesian mountainous villages with similarly shared community traits. However, further some locality aspects, including, but not limited to community leadership and economic power, need to be assessed further, as they play significant influences on the success of the program
Filling the gap: medium and large mammals from a Cerrado remnant in Central Brazil
Authors: Guimarães-Silva Marco Antonio , Barros Bittar Bruno , Fermino Beatriz , Vinhais Souza João Vitor , Vila de Carvalho Fabio Martins , Ribeiro de Morais Alessandro , Cordeiro Moreira Jãnio 
Published: July 2024

La diversidad del bioma Cerrado está amenazada por la deforestación y el reemplazo de la vegetación nativa por áreas agrícolas y urbanas. Desafortunadamente, áreas como parte del estado de Tocantins, permanecen como un vacío de muestreo para la fauna de mamíferos, que resulta en una falta de conocimiento. El presente estudio contribuye con información sobre mamíferos medianos y grandes de la región de Río Formoso, Tocantins. En enero de 2019, realizamos un levantamiento de campo en 7 puntos de muestreo en el municipio de Dueré, sur de Tocantins. Instalamos 4 cámaras trampa las cuales permanecieron activas por un periodo de 7 días. Adicionalmente, se realizaron censos activos diurnos y nocturnos. La relativa completitud del inventario se evaluó a través de las curvas acumulativas de las especies. Registramos 21 especies de mamíferos medianos y grandes durante 7 días de muestreo en una región bajo la influencia de actividades agrícolas, incluidas especies en peligro de extinción como jaguares, armadillos gigantes, nutrias gigantes y ciervos de los pantanos. La presencia de especies de mamíferos grandes y medianos, que tienen un papel importante en el ecosistema evidencia que el entorno local del Cerrado mantiene cierto equilibrio aún con las acciones antrópicas en el paisaje. Estos resultados muestran la importancia de los estudios de campo a nivel regional y brindan información sobre una región poco explorada.
The low chromosome number of a relict shrew (Cryptotis magnus) isolated in a cloud forest of México
Authors: Cervantes Fernando A. , Mata-González Stephanye , Ordaz-Téllez Ma. Guadalupe , Guevara Lázaro 
Published: July 2024

Para conocer y conservar a las musarañas mexicanas es necesario conocerlas bien, aunque su identificación taxonómica es difícil. Sin embargo, las herramientas citogenéticas pueden ayudar a discriminar las especies. No se conocen cariotipos de musarañas de México, por lo que decidimos iniciar el estudio de sus cromosomas comenzando con Cryptotis magnus. Se colectaron musarañas en bosque de niebla de Oaxaca y se prepararon metafases cromosómicas de médula ósea, se tiñeron con Giemsa, se examinaron microscópicamente y se fotografiaron. Se contaron los cromosomas para calcular el 2n, se determinó su morfología, se estimó el FN y se elaboró un cariotipo. Los especímenes de C. magnus fueron catalogados en la Colección Nacional de Mamíferos, Instituto de Biología, UNAM. Los resultados mostraron numerosas células metafásicas y cromosomas conspicuos. El número cromosómico diploide encontrado fue de 2n = 26, formado por 24 cromosomas autosómicos birrámeos (18 metacéntricos y 6 submetacéntricos) y 2 cromosomas sexuales (X: subtelocéntrico grande; Y: telocéntrico pequeño). Sumando el número de brazos cromosómicos de los autosomas el número fundamental (FN) resultante es 48. El complemento cromosómico de C. magnus es distintivo y su 2n es uno de los más pequeños de la familia Soricidae. La conformación actual de su perfil cromosómico puede haberse originado a partir de reordenamientos cromosómicos Robertsonianos que redujeron el 2n ancestral (46) a 2n = 26 produciendo autosomas de morfología birrámea. El aislamiento geográfico en una pequeña región geográfica de Oaxaca puede haber facilitado este proceso evolutivo.