bluuebunny/crossref_metadata_2025_split huggingface dataset:
MiR-653-5p drives osteoarthritis pathogenesis by modulating chondrocyte senescence
Authors: Lin Yucheng , Zhang Lu , Ji Mingliang , Shen Sinuo , Chen Yuzhi , Wu Shichao , Wu Xiaotao , Liu Nancy Q. , Lu Jun 
Published: May 2024

Abstract
Background
Due to the unclear pathogenesis of osteoarthritis (OA), effective treatment for this ailment is presently unavailable. Accumulating evidence points to chondrocyte senescence as a key driver in OA development. This study aims to identify OA-specific microRNAs (miRNAs) targeting chondrocyte senescence to alleviate OA progression.

Methods
We screened and identified miRNAs differentially expressed in OA and normal cartilage, then confirmed the impact of miR-653-5p on chondrocyte functions and senescence phenotypes through in vitro experiments with overexpression/silencing. We identified interleukin 6 (IL-6) as the target gene of miR-653-5p and confirmed the regulatory influence of miR-653-5p on the IL-6/JAK/STAT3 signaling pathway through gain/loss-of-function studies. Finally, we assessed the therapeutic efficacy of miR-653-5p on OA using a mouse model with destabilization of the medial meniscus.

Results
MiR-653-5p was significantly downregulated in cartilage tissues and chondrocytes from OA patients. Overexpression of miR-653-5p promoted chondrocyte matrix synthesis and proliferation while inhibiting chondrocyte senescence. Furthermore, bioinformatics target prediction and the luciferase reporter assays identified IL-6 as a target of miR-653-5p. Western blot assays demonstrated that miR-653-5p overexpression inhibited the protein expression of IL-6, the phosphorylation of JAK1 and STAT3, and the expression of chondrocyte senescence phenotypes by regulating the IL-6/JAK/STAT3 signaling pathway. More importantly, the cartilage destruction was significantly alleviated and chondrocyte senescence phenotypes were remarkably decreased in the OA mouse model treated by agomiR-653-5p compared to the control mice.

Conclusions
MiR-653-5p showed a significant decrease in cartilage tissues of individuals with OA, leading to an upregulation of chondrocyte senescence phenotypes in the articular cartilage. AgomiR-653-5p emerges as a potential treatment approach for OA. These findings provide further insight into the role of miR-653-5p in chondrocyte senescence and the pathogenesis of OA.
The effect of illness perception on psychosocial adjustment of patients with breast cancer and their spouses: actor–partner independence model
Authors: Wang Yan-feng , Liu An-kang , Dai Jin-zhen , Zhang Ji-ping , Chen Hui-hua , Jiang Xiao-hao , Tang Lu , He Yong-yue , Yang Qiao-hong 
Published: May 2024

Abstract
Objective
With the increase in the prevalence rate and improvements in the survival of breast cancer patients, there is a growing interest in understanding the level of psychosocial adjustment in these patients. The study aimed to describe the illness perception and psychosocial adjustment levels of both breast cancer patients and their spouses, to use the Actor-Partner Interdependence Model (APIM) to clarify the actor-partner relationships between spouses, and to explore the impact of illness perception on psychosocial adjustment to the disease within the joint actions of both spouses.

Methods
A total of 216 female patients with breast cancer and their spouses participated in the study. They were selected from two tertiary hospitals in Guangdong Province, China from October 2022 to May 2023 using a convenience sampling method. The participants were assessed using the Brief Illness Perception Questionnaire and the Psychosocial Adjustment to Illness Scale to examine the relationship between illness perception and psychosocial adjustment. AMOS24.0 was used to test and analyze the actor-partner interdependence model.

Results
The illness perception score (57.75 ± 10.91) was slightly higher than that of the spouse (57.10 ± 11.00), and the psychosocial adjustment score (64.67 ± 6.33) was slightly lower than that of the spouse (64.76 ± 7.49). The results of the actor-partner interdependence model indicated that there was a couple partner between breast cancer patients and their spouses: the spouse’s illness perception significantly affected the patient’s psychosocial adjustment (β = 0.095, p = 0.015); the patient’s illness perception also significantly affected the spouse’s psychosocial adjustment (β = 0.106, p = 0.033). Among them, the patient’s psychosocial adjustment was found to be related to the patient’s illness comprehensibility or coherence of illness (β = 0.433, p = 0.009), the spouse’s emotional illness representation (β = 0.218, p = 0.037), and the spouse’s illness comprehensibility or coherence of illness (β = 0.416, p = 0.007), while the spouse’s psychosocial adjustment was only related to the spouse’s illness comprehensibility or coherence of illness (β = 0.528, p = 0.007).

Conclusions
The psychosocial adjustment of breast cancer patients is affected by both their own and spouse’s illness perception. Therefore, in the future, the healthcare staff can implement early psychological interventions for patients diagnosed with breast cancer and their spouses as a unit to promote the psychosocial adjustment of them.
Laparoscopic surgery for De Garengeot’s hernia in a man after inguinal hernia surgery with a mesh plug: a case report and review of literature
Authors: Fujihata Shiro , Kuzuya Hiromasa , Kurimoto Masaaki , Shibata Tadashi , Sawai Hirozumi , Takiguchi Shuji 
Published: May 2024

Abstract
Background
De Garengeot’s hernia is a rare case of a femoral hernia that contains the appendix. Here we report a case of De Garengeot’s hernia that occurred in a male patient who had a history of inguinal hernia surgery using a mesh plug. There were no reports of De Garengeot’s hernia with a history of surgery for inguinal hernia, and the surgical question was whether we could successfully treat a patient with minimally invasive laparoscopic surgery using a mesh.

Case presentation
This case involved 75-year-old man with a history of right indirect inguinal hernia surgery using a mesh plug without on-lay mesh, who presented with a 5-day history of a right groin lump. Abdominal CT revealed an incarcerated appendix within the right femoral hernia and fluid collection around the appendix. Laparoscopic surgery was initiated and the incarcerated appendix was released with traction. There was no contamination around the appendix or the femoral ring, the appendix was removed, and the femoral hernia was repaired using mesh. Laparoscopic surgery was useful in first evaluating the inflammatory status of the appendix. As it was determined that there was little inflammation around the appendix and femoral ring, it was possible to repair the hernia using mesh.

Conclusions
De Garengeot’s hernias are rare and there is currently no standardized approach. Even if it is a recurrent hernia in the groin, laparoscopic surgery can be useful for diagnosis and treatment, but the use of mesh requires further careful consideration.
Interaction between urbanization and carbon emission in Guizhou Province
Authors: Jia Jingjing 
Published: May 2024

AbstractInvestigating interplay between urbanization and carbon emissions is crucial for reaching carbon peak objective. This study employs a VAR model to examine correlation between the urbanization rate and carbon emissions specifically within Guizhou Province, VAR model has obvious advantages in studying the dynamic relationship between them. The findings indicate that: (1) In Guizhou Province, there is a nuanced interplay between the urbanization rate and carbon emissions, with the magnitude and direction of their influence varying across different time intervals. (2) Carbon emissions in Guizhou Province exhibit a notable self-propelling effect, while concurrently, the urbanization rate demonstrates an inertia effect, which also contributes to its own advancement. (3) The influence of the urbanization rate on carbon emissions in Guizhou Province experiences gradual rise before plateauing, suggesting that the high-quality advancement of new urbanization in the region facilitates the achievement of carbon reduction objectives. Finally, policy recommendations are put forward: (1) Conscientiously implement the central ecological environment zoning control policies, such as: Guizhou Province Ecological environment zoning control Plan and Guizhou Province Urban and Rural Construction Carbon peak Implementation Plan and other policies. (2) Pay attention to the quality of Guizhou’s urbanization process. Solve the relationship between urbanization and carbon emissions, and realize the coordination and unification of urbanization and the carrying capacity of resources and environment. (3) Develop a new type of urbanization rich in Guizhou’s mountainous characteristics and promote the construction of low-carbon cities. Give full play to the regional characteristics of Guizhou’s mountainous areas, build a new type of urbanization with Guizhou’s mountainous characteristics, promote the construction of low-carbon cities in the process of urbanization development, and strengthen the coordinated development of ecological environment construction and urbanization.
To compare the HOMA-IR and metabolic profile in lean and obese subjects with non-alcoholic fatty liver disease
Authors: Nair Meenu C. , Stanley Lanord , Sivan Gisha , Kumar Janardanan Subramonia 
Published: May 2024

Abstract
Background and objective
Non-alcoholic fatty liver disease (NAFLD) is primarily perceived as a condition prevalent among obese individuals. Its pathogenesis is closely intertwined with metabolic syndrome components. However, the association between insulin resistance and NAFLD in nonobese individuals remains ambiguous. Observational studies have scrutinized the prevalence of insulin resistance and metabolic syndrome in lean NAFLD patients.

Materials and methods
This is an observational study, and NAFLD screening was carried out among inpatient and outpatient attendees at SRM Medical College’s General Medicine Department. Out of 200 screened patients meeting inclusion and exclusion criteria, 80 were diagnosed with non-alcoholic fatty liver disease (NAFLD). The assessment of metabolic syndrome was performed using the NCEP-ATP III criteria, allowing for comparison between groups concerning insulin resistance and metabolic parameters.

Results
Among NAFLD patients, those in the obese age group exhibited a higher prevalence of hypertension (57.8%; p < 0.001) and metabolic syndrome (75.6%; p < 0.0001). The lean NAFLD group showed elevated HOMA-IR levels (4.16) compared to obese NAFLD patients (2.92), with a significant statistical disparity (p < 0.0001). Additionally, the HSI value significantly increased in obese NAFLD patients (p < 0.00001).

Conclusion
Insulin resistance, a key factor in metabolic syndrome, is prevalent in lean individuals with non-alcoholic fatty liver disease (NAFLD), playing a pivotal role in its development. This resistance, linked to metabolic syndrome, promotes hepatic triglyceride and fatty acid accumulation, leading to NAFLD. Moreover, insulin resistance correlates significantly with weight gain in NAFLD patients.
Primary results from PATRICIA cohort C (SOLTI-1303), a randomized phase II study evaluating palbociclib with trastuzumab and endocrine therapy in pretreated HER2-positive and PAM50 luminal advanced breast cancer.
Authors: Ciruelos Eva , Pascual Tomás , Villacampa Guillermo , Pernas Sonia , Sanchez-Bayona Rodrigo , Ponce-Lorenzo Jose Juan , Cantos Sanchez de Ibarguren Blanca , Escrivá-de-Romaní Santiago , Perello Antonia , Montaño Alvaro , Martinez Eduardo , López González Ana , Melé Olivé Mireia , De La Haba Juan , Cortes Javier , Oliveira Mafalda , Villanueva Lorea , Gonzalez Xavier , Villagrasa Patricia , Prat Aleix 
Published: May 2024

1008 Background: The PATRICIA trial (cohorts A-B) demonstrated that palbociclib plus trastuzumab (T) is safe and active in patients (pts) with T-pretreated HER2-positive Hormone Receptor-positive (HR+/HER2+) PAM50 Luminal advanced breast cancer (ABC). Here, we present the primary efficacy analysis of the randomized cohort C from the PATRICIA trial that compares the efficacy of palbociclib + T + endocrine therapy (ET) with treatment of physicians’ choice (TPC). Methods: PATRICIA (cohort C) is a randomized, open-label, phase II study conducted at 34 sites in Spain recruiting from August 2019 to August 2023. Pts with HER2+/HR+ and centrally tested PAM50 Luminal A or B intrinsic subtype ABC who had received at least one prior line of anti-HER2 based regimens were eligible. Pts were randomized 1:1 to Cohort C1 (Palbociclib 125 mg/day orally 3 weeks/1 week off + T + ET) or Cohort C2 (TPC, including T + any ET or chemotherapy (CT) + T, or T-DM1). The stratification factors were number of previous regimens for ABC and presence of visceral disease. The primary endpoint was progression-free survival (PFS). The trial was designed to recruit a total of 102 pts, having an 80% power with one-sided alpha=0.1 to detect a HR of 0.62 in favor of the palbociclib cohort. The study was closed after 73 pts were randomized due to slow recruitment. Results: At data cut-off, 264 pts were pre-screened, and 73 pts were randomized. Baseline pts characteristics are summarized in Table 1. In cohort C1, 50% of the pts received fulvestrant and 50% aromatase inhibitor as ET. In cohort C2, 37.1% of pts were treated with TDM-1, 45.7% with CT+ T, 11.4 % with ET + T and two pts withdrew their consent before starting the treatment. Palbociclib + T + ET was associated with longer PFS compared to TPC (median 9.1 vs 7.5 months, stratified HR=0.52 [95%CI 0.29-0.94]; two-sided p=0.031); 12-months PFS rates were 43.7% and 21.4%, respectively. The overall response rate was 18.9% (95% CI 8.6-35.7) in cohort C1 and 8.3% (95% CI 1.4-28.5) in cohort C2. Grade ≥3 adverse events occurred in 63.2% of pts in C1 and 45.5% in C2 cohort. The most frequent grade ≥3 adverse event in the experimental arm was neutropenia (55.3%). Conclusions: The combination of palbociclib, T and ET showed a statistically significant improvement in PFS in patients with previously treated PAM50 luminal A or B HER2+ advanced breast cancer, as compared to TPC. Clinical trial information: NCT02448420 . [Table: see text]
Real-world and clinical trial validation of a deep learning radiomic biomarker for PD-(L)1 immune checkpoint inhibitor response in stage IV NSCLC.
Authors: Sako Chiharu , Duan Chong , Maresca Kevin , Kent Sean , Aerts Hugo , Parikh Ravi Bharat , Simon George R. , Jordan Petr 
Published: May 2024

102 Background: Immune checkpoint inhibitor (ICI) therapy is standard-of-care for treatment of mutation-negative advanced non-small cell lung cancer (NSCLC). However, given known inaccuracy of PD-(L)1 markers, there is an unmet need to better identify patients most likely to derive clinical benefit from ICI. We developed and externally validated a generalizable CT imaging-based biomarker to predict response to ICI. Methods: We developed and validated a deep learning radiomic biomarker using an internally curated real-world dataset (RWD) of 2,010 stage IV NSCLC patients treated with PD-(L)1 ICIs in academic and community settings from US and Europe. Patients with missing baseline imaging, missing follow-up data, or EGFR/ALK oncogenic driver mutations were excluded, resulting in a total of 1,188 subjects. This RWD consisted of a discovery cohort (Dataset A, N=844) and a temporally distinct holdout cohort (Dataset B, N=344), which were used to generate performance metrics of the biomarker. To test generalizability, we validated our biomarker in a prospective clinical trial dataset evaluating Sasanlimab in PD-(L)1 therapy-naïve, advanced NSCLC patients (NCT02573259, Dataset C, N=54). We utilized a two-stage learning approach to model 6-month PFS. First, we used an independent multi-task deep-learning feature extractor trained on 19,184 whole chest CT scans. Second, we input the extracted features into a Cox proportional hazard (CoxPH) model along with age, sex, and baseline lesion measurements (sum of longest diameter and distant metastases counts), and the model generated a time-dependent PFS function and a response score. We performed 6-fold cross-validation on Dataset A to train and evaluate the models, which were subsequently ensembled and applied to independent Datasets B and C. To assess independence from PD-L1 status and key demographic covariates, we herein report multivariate adjusted hazard ratios (HR) for the group identified as low-risk based on the biomarker. Results: In Dataset A, the biomarker showed a cross-validation PFS adjusted HR of 0.49 (95% CI 0.38-0.63) in the all-comers cohort and 0.28 (0.17-0.46) in the first-line ICI monotherapy cohort (1LMono). In Dataset B, the PFS adjusted HRs were 0.54 (0.35-0.83) in all-comers and 0.18 (0.05-0.61) in 1LMono. In Dataset C, the adjusted HRs were 0.30 (0.14-0.68) for PFS, 0.29 (0.10-0.83) for OS, 0.31 (0.14-0.72) for TTP. Conclusions: In our validations in RWD and clinical trial cohorts, a deep-learning radiomic biomarker based on routine pre-treatment CT scans predicted response to ICI and stratified patients independently from PD-L1 status. This tool may inform clinical decision-making, such as to help guide whether concomitant chemotherapy may not be needed. In future work, we plan to further validate our approach in larger prospective datasets and expand its use to new indications.
Efficacy of alpelisib (ALP) + fulvestrant (FUL) with rational use of metformin (MET) in patients with HR+/HER2- advanced breast cancer (ABC).
Authors: Filonenko Daria , Orlova Rashida , Gluzman Mark , Vakhitova Almira , Goryainova Alla , Grechukhina Katerina , Bykonya Irina , Zhukova Lyudmila 
Published: May 2024

1049 Background: Hyperglycemia (HG) is an on-target effect of ALP, and prophylactic with metformin was shown to decrease the rate and severity of HG. Here we present efficacy and safety of ALP in a large cohort of patients with rational approach to metformin usage based on risk factors of HG. Methods: Patients (pts) with HR+/HER2- PIK3CAmut ABC were treated with ALP 300mg orally and FUL 500mg IM until disease progression or intolerance. The primary endpoints were progression free survival (PFS) and rate of grade 3/4 HG in different risk groups. Pts were stratified to risk groups of HG based on the algorithm (table 1) before starting ALP and received MET for prevention of HG. Results: A cohort comprised 139 pts, median lines of previous treatment in ABC was 3 (1-9): 88% received CDK4/6i, 60% - FUL, and 55% - chemotherapy (77) prior to ALP. The median PFS (mPFS) on ALP - was 7.0 (CI 95%: 5.0-8.9). The risk of HG was assessed in 138 pts: low (47), moderate (46), and high (42) risk, and 3 pts with type 2 diabetes mellitus. Any grade HG was reported in 62% pts, no cases HG G4 were detected. HG G3 was reported in 13% pts; 10% pts required ALP dose reduction to 250 mg due to HG G3; 3 pts (2%) discontinued ALP due to HG. The mPFS in our analysis was longer than in BYlieve trial in cohort C: 7.0 vs 5.6 mo. We suggest that prophylactic of HG allowed maintenance of full dose of ALP in most patients and thus increased the efficacy of ALP. Furthermore, in contrast to the METALLICA trial we distinguished a low risk group (33%) of pts who don’t need the prophylactic use of MET. Conclusions: Rational use of MET in pts with moderate and high risk of HG reduces the frequency and severity of HG, decreases the rate of ALP dose reductions and as a result may increase the efficacy of ALP. Pts with low risk of HG don’t need MET for HG prevention. [Table: see text]
Association of immune checkpoint inhibitor introduction and changes in survival disparities by health insurance coverage among individuals newly diagnosed with advanced cancers in the US.
Authors: Zhao Jingxuan , Graetz Ilana , Howard David , Yabroff Robin , Lipscomb Joseph 
Published: May 2024

1580 Background: First approved by the US Food and Drug Administration (FDA) in 2011, immune checkpoint inhibitors (ICIs) have transformed treatment options for many cancers. Unfortunately, due to their high cost, individuals without health insurance coverage may not be able to afford them. Therefore, the introduction of ICIs may lead to greater disparities in cancer survival between patients with and without health insurance. This study examined the association of health insurance with changes in survival disparities associated with the introduction of ICIs. Methods: We identified individuals newly diagnosed at age 18-64 years at stage IV with any one of the following cancers with FDA approval for ICI treatment, including melanoma (first approved 03/25/2011, n=9992); HR+ HER- female breast cancer (02/03/2015, n=13632); non-small cell lung cancer (NSCLC; 03/04/2015, n=113866); and renal cell carcinoma (RCC; 11/23/2015, n=15403) from the National Cancer Database. Individuals with private health insurance or who were uninsured at the time of the cancer diagnosis were included. For each cancer, we applied a difference-in-differences (DD) approach to examine the changes in two-year overall survival before and after the ICI FDA approval date among individuals without health insurance compared to those with private health insurance, using flexible parametric survival models and controlling for key sociodemographic factors. Results: As shown (Table), among patients diagnosed with melanoma, 2-year survival rate increased from 16.33% pre-ICI approval to 27.04% after ICI approval among patients who were uninsured and increased from 28.22% to 45.45% among patients with private health insurance, with the disparity by health insurance status widened by 4.58 (95% confidence interval [CI] = 0.02 to 9.14) percentage points (ppt) after adjusting for sociodemographic factors. For patients diagnosed with stage IV NSCLC, the disparity by health insurance widened by 1.58 (95% CI = 0.52 to 2.64) ppt. Conclusions: The introduction of ICIs increased disparities in survival by health insurance status. Policies to improve health insurance coverage options or make new treatments more affordable to uninsured patients are needed. [Table: see text]