bluuebunny/crossref_metadata_2025_split huggingface dataset:
WITHDRAWN: Development and Validation of a Pathomics Model for Accurate Grading of Pancreatic Neuroendocrine Tumors Short title: Pathomics Model for Grading of PNETs
Authors: ying li , Chen Chengwei , Zhang Yunshuo , Yu Jieyu , Fang Xu , Liu Fang , Wang Tiegong , Li Jing , Wang Li , Lu Jianping , Jiang Hui , Shao Chengwei , Bian Yun 
Published: December 2024

Abstract

Background
Accurate detection of the histological grade of pancreatic neuroendocrine tumors (PNETs) is important for patients’ prognoses and treatment. Traditional grading methods based on mitotic count and Ki-67 index are subjective and time-consuming. Our aim is to develop and validate a pathomics model for precise grading of PNETs, utilizing digital histopathological features derived from H&E-stained sections.
Methods
This retrospective study comprehensively reviewed the clinical data of 272 PNET patients who underwent surgical resection. Pathomics features were extracted from H&E whole slide images (WSIs) using Lasso regression to create a pathomics score. Two multivariate logistic regression models—a clinical model and a pathomics model—were developed to predict G grades, constructing a nomogram. Model performance was evaluated using ROC curves. Kaplan-Meier analysis compared survival curves, with statistical significance assessed using the log-rank test.
Findings
A total of 272 patients were enrolled: 160 with G1 (mean age 54 ± 11, 90 men) and 112 with G2/G3 (mean age 52 ± 12, 55 men). The dataset was divided into training (149 patients), validation (65 patients), and test sets (58 patients). Among 427 pathomics features, six optimal features were selected to calculate the pathomics score. This score was significantly associated with PNET grade and could differentiate between high- and low-risk groups. In the validation and test sets, the pathomics model, which combined the pathomics score with clinical features, achieved AUCs of 0.85 and 0.93, respectively. It outperformed the clinical model, which had AUCs of 0.83 and 0.77 in the validation and test sets, respectively. Notably, patients predicted to have high-grade PNETs by the pathomics model exhibited a significantly shorter progression-free survival compared to those with low-grade tumors, and the pathomics model-predicted G2/3 was an independent predictor for worse progression-free survival (HR, 17.59; 95% CI: 1.99-155.83; P = 0.01).
Interpretation
Our study presents a highly accurate pathomics model for predicting PNETgrades using H&E-stained sections, enhancing data processing efficiency and providing a quantitative assessment of histological features. This model holds promise for guiding individualized treatment and risk stratification in PNET management.
Funding
This work was supported in part by the National Science Foundation for Scientists of China (81871352, 82171915, 82171930, 82271972, 62402501 and 82371955), The Natural Science Foundation of Shanghai Science and Technology Innovation Action Plan (21ZR1478500 and 21Y11910300), China Postdoctoral Science Foundation Funded Project (2023M734270) and Clinical Research Plan of SHDC (SHDC2022CRD028).
Syndecan-4 promotes gastric cancer progression through activating TGF-β1 induced lipid reprogramming and contributes positive loop circuits
Authors: Liu Guangjie , Jia Ru , Deng Heng , Wang Xiaoshan 
Published: December 2024

Abstract

Background
Syndecan-4 (SDC4) plays a pivotal role in tumorigenesis. Lipid reprogramming is utilized by tumor cells to maintain rapid proliferation, migration, and invasion. Therefore, it is important to investigate novel therapeutic targets and mechanisms in gastric cancer (GC).
Methods
Clinicopathological data and corresponding immunohistochemistry data were collected to explore the role of SDC4 in patients with GC. Cell progression and lipid reprogramming were assessed using functional experiments, and the molecular mechanisms involved were determined using western blotting. Moreover, cholesterol-induced lipotoxic environments in vivo and in vitro were constructed to explore the underlying positive loop circuit.
Results
SDC4 expression was upregulated in GC tissues compared to that in normal tissues and was associated with tumor differentiation. GC patients with high SDC4 expression were positively correlated with high circulating tumor cell (CTC) and vascular endothelial growth factor (VEGF) levels. Moreover, SDC4 significantly promotes cell progression by activating transforming growth factor-beta 1 (TGF-β1/TGFB1)-induced lipid synthesis and contributes to a positive loop circuit in GC cells. However, the core of this circuit is dependent on Smad3. In addition, a cholesterol-induced lipotoxic environment further upregulated SDC4 expression by activating the RAS signaling pathway in GC.
Conclusions
These findings highlight SDC4 as a therapeutic target for GC and identify actionable positive loop circuits.
The association between low skeletal muscle mass and immunoinflammatory markers in middle-aged and elderly patients with type 2 diabetes mellitus
Authors: Guo Xinyuan , Pan Binjing , Han Mei , Ma Dengrong , Zan Xiaohui , Liu Jingfang 
Published: December 2024

Abstract

Purpose
To investigate the relationships between low skeletal muscle mass and immunoinflammatory markers in middle-aged and elderly patients with type 2 diabetes mellitus (T2DM).
Methods
From April 2022 to May 2023, 978 middle-aged and elderly T2DM patients diagnosed in the Department of Endocrinology of the First Hospital of Lanzhou University were divided into a low skeletal muscle mass group and a normal group according to the muscle mass index, compared the differences between the groups. The above immunoinflammatory markers were grouped according to the quartile levels, and the prevalences of muscle mass loss were compared among the groups; the relationship between the immunoinflammatory index and low skeletal muscle mass in T2DM patients was analysed.
Results
Compared with the normal group, the levels of all immunoinflammatory indices of low skeletal muscle mass group were significantly increased ( P < 0.05); the prevalences of skeletal muscle mass loss were progressively raised with increasing quartile levels of each immunoinflammatory marker. The levels of immunoinflammatory markers were independently and positively correlated with the risk of low skeletal muscle mass (NAR: OR = 2.148, 95% CI 1.225–3.766, P = 0.008; NLR: OR = 1.210, 95% CI 1.036–1.411, P = 0.016; MLR: OR = 1.282, 95% CI 1.068–1.540, P = 0.008; SII: OR = 1.001, 95% CI 1.000 -1.002, P = 0.009; SIRI: OR = 1.828, 95% CI 1.271–2.628, P = 0.001; SIRI: OR = 1.003, 95% CI 1.001–1.004, P = 0.010) .
Conclusions
The occurrence of low skeletal muscle mass may be closely related to immune inflammation in middle-aged and elderly T2DM patients. Monitoring immune inflammation markers is of clinical value for early screening and intervention of muscle mass loss in middle-aged and elderly T2DM patients.
Epigenetic Alterations and Microbiota Changes in the Saliva of Individuals With Binge-Eating Spectrum Disorders Compared With Normal Weight Healthy Controls
Authors: Mercante Francesca , Abbaspour Afrouz , Pucci Mariangela , Sabatucci Annalaura , Rania Marianna , Konstantinidou Fani , Gatta Valentina , Stuppia Liborio , Cifani Carlo , Bulik Cynthia M. , Garcia Cristina-Segura , D’Addario Claudio 
Published: December 2024

Abstract

Background
Binge-eating spectrum disorders, including bulimia nervosa (BN) and binge-eating disorder (BED), have psychological, behavioral, and physical effects, which present significant challenges for accurate diagnosis and treatment. Identifying biomarkers is thus of relevance to improve diagnostic and treatment strategies.
Methods
Saliva collected from female individuals with BED (n = 20), BN (n = 17), and normal weight healthy controls (NW-HC) (n = 20) was analyzed to assess salivary microbiome, exosomal miRNA expression, and DNA methylation of dopaminergic system gene components.
Results
Microbial diversity was significantly reduced in BED and BN groups compared to NW-HC. Differential abundance analysis revealed that Bacilli (class-level) were enriched in BN and BED, while Lachnospirales (order-level) were significantly depleted in BN compared to NW-HC. In total, 79 miRNAs resulted differentially expressed in patients compared with controls. Alteration in four of these miRNAs (let-7b-5p, mir-15b-5p, mir-429, and mir-221-3p) identified via network analysis as potentially relevant to psychiatric disorders, were confirmed to be significantly upregulated in both BED and BN compared with controls. Significant hypomethylation at specific CpG sites of the DAT1 gene was also observed in BED and BN groups relative to controls. Correlation analysis highlighted significant associations between specific microbiota genera, miRNA expression, and DNA methylation of DAT1 in both the BED and BN groups.
Conclusions
Our findings provide new evidence on the role of epigenetic modifications linked to alterations in salivary microbial composition and diversity in BED and BN, opening new avenues for future research and therapeutic interventions in eating disorders targeting miRNAs and microbiota.
Effectiveness of the combination of netupitant and palonosetron in the prevention of nausea and vomiting during anthracycline-containing chemotherapy in patients with breast cancer
Authors: Grechukhina K. S. , Kolyago E. M. , Kalugin M. V. , Zhukova L. G. 
Published: December 2024

The incidence of early-stage breast cancer among young patients has shown a significant increase over the past twenty years, with a substantial portion of these patients requiring chemotherapy. Most treatment regimens used in both neo-adjuvant and adjuvant settings are characterized as moderately or highly emetogenic. Young patients typically lead socially active lives, balancing work and childcare, and strive to remain indistinguishable from healthy women. However, one of the most pronounced adverse effects of chemotherapy is nausea and vomiting, which significantly impair quality of life. One modern method for the prevention of nausea and vomiting involves the use of a combined NK1-receptor and 5-HT3-receptor antagonist, comprising the drugs netupitant and palonosetron (NEPA). This medication is administered as a single dose on the first day in conjunction with dexamethasone, without the need for additional medication on subsequent days. This review discusses the mechanisms of action of NEPA and pres ents studies focused on the effectiveness of the combination of netupitant and palonosetron in patients undergoing moderately and highly emetogenic therapy. According to literature the efficacy of NEPA in combination with dexamethasone reached 70.5% for complete response in the first cycle of treatment. A retrospective analysis involving 2,173 patients confirmed the high efficacy of NEPA, particularly in patients under 60 years of age. Data from real clinical practice further support the results of studies on the effectiveness of NEPA, demonstrating a complete control rate of nausea and vomiting ranging from 74 to 90%.
Efficacy and safety of lorlatinib as first-line treatment for advanced ALK-mutated non-small cell lung cancer: A clinical case study
Authors: Kornietskaya А. L. , Evdokimova S. F. , Bolotina L. V. , Rodionov E. O. , Fedenko A. A. 
Published: December 2024

In recent years, approaches to the pharmacological treatment of non-small cell lung cancer (NSCLC) have significantly evolved due to a deeper understanding of tumor biology and, consequently, the active development of personalized medicine and the introduction of targeted therapies. The identification of activating mutations, including ALK gene rearrangements, enables long-term objective control, which is particularly crucial in young patients with extensive metastatic disease and brain metastases (BM). The high rate of central nervous system (CNS) metastases characteristic of ALK-positive NSCLC underscores the importance of selecting therapeutic agents with high intracranial activity. Lorlatinib, a third-generation ALK tyrosine kinase inhibitor (TKI), is capable of crossing the blood-brain barrier and effectively suppressing resistance mutations that may develop during treatment with crizotinib or second-generation TKIs. Initially, lorlatinib was used in the second-line and subsequent lines of therapy; however, updated results from the CROWN study have demonstrated its unprecedented efficacy as a first-line treatment, including in patients with BM. Currently, lorlatinib is approved in the Russian Federation for the treatment of ALK-positive advanced NSCLC in both previously treated patients and as a first-line therapy. This paper presents a clinical case of a 49-yearold patient with advanced ALK-positive NSCLC and brain metastases. Following the diagnostic phase, which included videoassisted thoracoscopy and morphological verification, the patient underwent a course of chemotherapy with cisplatin and pemetrexed. Subsequently, based on the results of molecular genetic testing, lorlatinib was initiated at a dose of 100 mg/day. Within a month, a significant regression of CNS metastases was observed. Therapy was accompanied by minimal side effects, including hypercholesterolemia and elevated liver enzymes, which were successfully managed with lipid-lowering agents and physical activity. During targeted therapy, the patient has maintained stable disease for 26 months, showing a strong clinical response without the need for dose reduction. This case report highlights the efficacy and tolerability of lorlatinib in the treatment of ALK-positive NSCLC with BM and underscores its potential in clinical practice.
Efficiency of detoxifying enteral nutrition therapy in oncological palliative patients
Authors: Pilat T. L. , Shaymardanov I. V. , Novikov G. A. , Hidiyatov I. R. , Shaikhutdinov N. G. , Gazizov R. A. , Battalov I. M. 
Published: December 2024

Introduction. Palliative care is an approach aimed at improving the quality of life of patients and their families. Palliative patients, including oncological ones, have pronounced manifestations of intoxication, body weight deficiency, loss of muscle mass, which leads to weakness, asthenization, decreased motor activity, and the inability to maintain a habitual lifestyle.Aim. To evaluate the effectiveness and safety of the impact of nutritional support for palliative patients by including in the diet a specialized product of dietary therapeutic and dietary preventive nutrition Protein detoxification cocktail of domestic production.Materials and methods. The study involved 60 palliative patients of both sexes, the data from questionnaires on the organoleptic properties and parameters of the functional activity of patients, as well as clinical and biochemical studies of blood, liver functions after a 30-day intake of a detoxifying food product were examined.Results. The studies showed good tolerability, safety and excellent organoleptic properties of the therapeutic Protein Detoxifying Cocktail. Patients noted an improvement in their general condition, a decrease in weakness, an increase in physical activity, mobility and the ability to move, the ability to take care of themselves, engage in normal activities, an improvement in appetite and a decrease in bowel disorders, a decrease in pain and discomfort, anxiety and depression, and an improvement in sleep. Analysis of laboratory data showed that in the main group of palliative patients, there was an increase in the level of hemoglobin, hematocrit, total protein and albumin, as well as a decrease in such indicators as: CRP, creatinine, urea, bilirubin.Conclusions. The study demonstrates the effectiveness of detoxifying therapeutic enteral nutrition in oncological palliative patients. Detoxifying therapeutic enteral nutrition not only improves metabolism and protein-energy status of patients, but also improves the quality of life and overall survival due to detoxifying, antioxidant, restorative, anti-inflammatory, analgesic and general tonic effects.
Laypeople’s Use of and Attitudes Toward Large Language Models and Search Engines for Health Queries: Survey Study
Authors: Mendel Tamir , Singh Nina , Mann Devin M , Wiesenfeld Batia , Nov Oded 
Published: December 2024

Background
Laypeople have easy access to health information through large language models (LLMs), such as ChatGPT, and search engines, such as Google. Search engines transformed health information access, and LLMs offer a new avenue for answering laypeople’s questions.

Objective
We aimed to compare the frequency of use and attitudes toward LLMs and search engines as well as their comparative relevance, usefulness, ease of use, and trustworthiness in responding to health queries.

Methods
We conducted a screening survey to compare the demographics of LLM users and nonusers seeking health information, analyzing results with logistic regression. LLM users from the screening survey were invited to a follow-up survey to report the types of health information they sought. We compared the frequency of use of LLMs and search engines using ANOVA and Tukey post hoc tests. Lastly, paired-sample Wilcoxon tests compared LLMs and search engines on perceived usefulness, ease of use, trustworthiness, feelings, bias, and anthropomorphism.

Results
In total, 2002 US participants recruited on Prolific participated in the screening survey about the use of LLMs and search engines. Of them, 52% (n=1045) of the participants were female, with a mean age of 39 (SD 13) years. Participants were 9.7% (n=194) Asian, 12.1% (n=242) Black, 73.3% (n=1467) White, 1.1% (n=22) Hispanic, and 3.8% (n=77) were of other races and ethnicities. Further, 1913 (95.6%) used search engines to look up health queries versus 642 (32.6%) for LLMs. Men had higher odds (odds ratio [OR] 1.63, 95% CI 1.34-1.99; P<.001) of using LLMs for health questions than women. Black (OR 1.90, 95% CI 1.42-2.54; P<.001) and Asian (OR 1.66, 95% CI 1.19-2.30; P<.01) individuals had higher odds than White individuals. Those with excellent perceived health (OR 1.46, 95% CI 1.1-1.93; P=.01) were more likely to use LLMs than those with good health. Higher technical proficiency increased the likelihood of LLM use (OR 1.26, 95% CI 1.14-1.39; P<.001). In a follow-up survey of 281 LLM users for health, most participants used search engines first (n=174, 62%) to answer health questions, but the second most common first source consulted was LLMs (n=39, 14%). LLMs were perceived as less useful (P<.01) and less relevant (P=.07), but elicited fewer negative feelings (P<.001), appeared more human (LLM: n=160, vs search: n=32), and were seen as less biased (P<.001). Trust (P=.56) and ease of use (P=.27) showed no differences.

Conclusions
Search engines are the primary source of health information; yet, positive perceptions of LLMs suggest growing use. Future work could explore whether LLM trust and usefulness are enhanced by supplementing answers with external references and limiting persuasive language to curb overreliance. Collaboration with health organizations can help improve the quality of LLMs’ health output.
Electronic Health Record Use Patterns Among Well-Being Survey Responders and Nonresponders: Longitudinal Observational Study
Authors: Tawfik Daniel , Shanafelt Tait D , Bayati Mohsen , Profit Jochen 
Published: December 2024

Abstract

Background
Physician surveys provide indispensable insights into physician experience, but the question of whether responders are representative can limit confidence in conclusions. Ubiquitously collected electronic health record (EHR) use data may improve understanding of the experiences of survey nonresponders in relation to responders, providing clues regarding their well-being.

Objective
The aim of the study was to identify EHR use measures corresponding with physician survey responses and examine methods to estimate population-level survey results among physicians.

Methods
This longitudinal observational study was conducted from 2019 through 2020 among academic and community primary care physicians. We quantified EHR use using vendor-derived and investigator-derived measures, quantified burnout symptoms using emotional exhaustion and interpersonal disengagement subscales of the Stanford Professional Fulfillment Index, and used an ensemble of response propensity-weighted penalized linear regressions to develop a burnout symptom prediction model.

Results
Among 697 surveys from 477 physicians with a response rate of 80.5% (697/866), always responders were similar to nonresponders in gender (204/340, 60% vs 38/66, 58% women; P=.78) and age (median 50, IQR 40‐60 years vs median 50, IQR 37.5‐57.5 years; P=.88) but with higher clinical workload (median 121.5, IQR 58.5‐184 vs median 34.5, IQR 0‐115 appointments; P<.001), efficiency (median 5.2, IQR 4.0-6.2 vs median 4.3, IQR 0‐5.6; P<.001), and proficiency (median 7.0, IQR 5.4‐8.5 vs median 3.1, IQR 0‐6.3; P<.001). Survey response status prediction showed an out-of-sample area under the receiver operating characteristics curve of 0.88 (95% CI 0.77-0.91). Burnout symptom prediction showed an out-of-sample area under the receiver operating characteristics curve of 0.63 (95% CI 0.57-0.70). The predicted burnout prevalence among nonresponders was 52%, higher than the observed prevalence of 28% among responders, resulting in an estimated population burnout prevalence of 31%.

Conclusions
EHR use measures showed limited utility for predicting burnout symptoms but allowed discrimination between responders and nonresponders. These measures may enable qualitative interpretations of the effects of nonresponders and may inform survey response maximization efforts.