bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined versus independent effects of exercise training and intermittent fasting on body composition and cardiometabolic health in adults: a systematic review and meta-analysis
Authors: Khalafi Mousa , Symonds Michael E. , Maleki Aref Habibi , Sakhaei Mohammad Hossein , Ehsanifar Mahsa , Rosenkranz Sara K. 
Published: January 2024

AbstractIntroduction and aimExercise training (Ex) and intermittent fasting (IF) are effective for improving body composition and cardiometabolic health overweight and obese adults, but whether combining Ex and IF induces additive or synergistic effects is less well established. We therefore, performed a systematic review and meta-analysis to compare the combined versus independent effects of Ex and IF on body composition and cardiometabolic health in adults.MethodAn electronic search was conducted in three main online databases including PubMed, Web of Science, and Scopus, from inception to March 9, 2023 for studies involving Ex plus IF trials versus standalone Ex and/or IF interventions in adults. Interventions had a duration of ≥ 2 weeks. Standardized (SMD) or weighted mean differences (WMD) and 95% confidence intervals were calculated in order to compare effects on body weight, body mass index (BMI), body fat lean body mass (LBM), visceral fat, and waist circumference. For cardiometabolic health, outcomes included fasting glucose, insulin, total cholesterol (TC), low-density lipoprotein cholesterol (LDL), triglycerides (TG), high-density lipoprotein cholesterol (HDL), systolic (SBP) and diastolic (DBP) blood pressure, and VO2max/peak.ResultsEx plus IF decreased body weight [WMD: -3.03 kg (95% CI: -3.44 to -2.61),p = 0.001], BMI [WMD: -1.12 kg.m2(95% CI: -1.28 to -0.95),p = 0.001], body fat [SMD: -0.72 (95% CI: -1.23 to -0.21),p = 0.005], visceral fat [SMD: -0.34 (95% CI: -0.63 to -0.05),p = 0.01], and waist circumference [WMD: -2.63 cm (95% CI: -4.16 to -1.11),p = 0.001] more than Ex alone. However, changes in body composition and cardiometabolic health markers were not significantly different for Ex plus IF when compared with IF alone, with the exception of VO2max/peak [SMD: 0.55 (95% CI: 0.14 to 0.97),p = 0.009].ConclusionWe demonstrate that a combination of Ex and IF produces superior changes in body composition, but not in markers of cardiometabolic health when compared with Ex or IF alone. Ex plus IF could therefore be effective for weight and fat loss but has no additive or synergistic effects for other cardiometabolic health markers.
CircPPAP2B controls metastasis of clear cell renal cell carcinoma via HNRNPC-dependent alternative splicing and targeting the miR-182-5p/CYP1B1 axis
Authors: Zheng Zaosong , Zeng Xiangbo , Zhu Yuanchao , Leng Mengxin , Zhang Zhiyong , Wang Qiong , Liu Xiaocen , Zeng Siying , Xiao Yongyuan , Hu Chenxi , Pang Shiyu , Wang Tong , Xu Bihong , Peng Peidan , Li Fei , Tan Wanlong 
Published: January 2024

Abstract
Background
Renal cell carcinoma (RCC) is one of the most common malignant tumor worldwide. Metastasis is a leading case of cancer-related deaths of RCC. Circular RNAs (circRNAs), a class of noncoding RNAs, have emerged as important regulators in cancer metastasis. However, the functional effects and regulatory mechanisms of circRNAs on RCC metastasis remain largely unknown.

Methods
High-throughput RNA sequencing techniques were performed to analyze the expression profiles of circRNAs and mRNAs in highly and poorly invasive clear cell renal cell carcinoma (ccRCC) cell lines. Functional experiments were performed to unveil the regulatory role of circPPAP2B in the proliferation and metastatic capabilities of ccRCC cells. RNA pulldown, Mass spectrometry analysis, RNA methylation immunoprecipitation (MeRIP), RNA immunoprecipitation (RIP), co-immunoprecipitation (CoIP), next-generation RNA-sequencing and double luciferase experiments were employed to clarify the molecular mechanisms by which circPPAP2B promotes ccRCC metastasis.

Results
In this study, we describe a newly identified circular RNA called circPPAP2B, which is overexpressed in highly invasive ccRCC cells, as determined through advanced high-throughput RNA sequencing techniques. Furthermore, we observed elevated circPPAP2B in ccRCC tissues, particularly in metastatic ccRCC tissues, and found it to be associated with poor prognosis. Functional experiments unveiled that circPPAP2B actively stimulates the proliferation and metastatic capabilities of ccRCC cells. Mechanistically, circPPAP2B interacts with HNRNPC in a m6A-dependent manner to facilitate HNRNPC nuclear translocation. Subcellular relocalization was dependent upon nondegradable ubiquitination of HNRNPC and stabilization of an HNRNPC/Vimentin/Importin α7 ternary complex. Moreover, we found that circPPAP2B modulates the interaction between HNRNPC and splicing factors, PTBP1 and HNPNPK, and regulates pre-mRNA alternative splicing. Finally, our studies demonstrate that circPPAP2B functions as a miRNA sponge to directly bind to miR-182-5p and increase CYP1B1 expression in ccRCC.

Conclusions
Collectively, our study provides comprehensive evidence that circPPAP2B promotes proliferation and metastasis of ccRCC via HNRNPC-dependent alternative splicing and miR-182-5p/CYP1B1 axis and highlights circPPAP2B as a potential therapeutic target for ccRCC intervention.
Treatment in certified cancer centers is related to better survival in patients with colon and rectal cancer: evidence from a large German cohort study
Authors: Bierbaum Veronika , Bobeth Christoph , Roessler Martin , Gerken Michael , Tol Kees Kleihues-van , Reissfelder Christoph , Fürst Alois , Günster Christian , Dröge Patrik , Ruhnke Thomas , Klinkhammer-Schalke Monika , Schmitt Jochen , Schoffer Olaf 
Published: January 2024

Abstract
Background
Certified cancer centers aim to ensure high-quality care by establishing structural and procedural standards according to evidence-based guidelines. Despite the high clinical and health policy relevance, evidence from a nation-wide study for the effectiveness of care for colorectal cancer in certified centers vs. other hospitals in Germany is still missing.

Methods
In a retrospective cohort study covering the years 2009–2017, we analyzed patient data using demographic information, diagnoses, and treatments from a nationwide statutory health insurance enriched with information on certification. We investigated whether patients with incident colon or rectal cancer did benefit from primary therapy in a certified cancer center. We used relative survival analysis taking into account mortality data of the German population and adjustment for patient and hospital characteristics via Cox regression with shared frailty for patients in hospitals with and without certification.

Results
The cohorts for colon and rectal cancer consisted of 109,518 and 51,417 patients, respectively, treated in a total of 1052 hospitals. 37.2% of patients with colon and 42.9% of patients with rectal cancer were treated in a certified center. Patient age, sex, comorbidities, secondary malignoma, and distant metastases were similar across groups (certified/non-certified) for both colon and rectal cancer. Relative survival analysis showed significantly better survival of patients treated in a certified center, with 68.3% (non-certified hospitals 65.8%) 5-year survival for treatment of colon cancer in certified (p < 0.001) and 65.0% (58.8%) 5-year survival in case of rectal cancer (p < 0.001), respectively. Cox regression with adjustment for relevant covariates yielded a lower hazard of death for patients treated in certified centers for both colon (HR = 0.92, 95% CI = 0.89–0.95) and rectal cancer (HR = 0.92, 95% CI = 0.88–0.95). The results remained robust in a series of sensitivity analyses.

Conclusions
This large cohort study yields new important evidence that patients with colorectal cancer have a better chance of survival if treated in a certified cancer center. Certification thus provides one powerful means to improve the quality of care for colorectal cancer. To decrease the burden of disease, more patients should thus receive cancer care in a certified center.
Noninvasive electrical stimulation as a neuroprotective strategy in retinal diseases: a systematic review of preclinical studies
Authors: Li Jiaxian , Zhou Wei , Liang Lina , Li Yamin , Xu Kai , Li Xiaoyu , Huang Ziyang , Jin Yu 
Published: January 2024

AbstractBackgroundElectrical activity has a crucial impact on the development and survival of neurons. Numerous recent studies have shown that noninvasive electrical stimulation (NES) has neuroprotective action in various retinal disorders.ObjectiveTo systematically review the literature on in vivo studies and provide a comprehensive summary of the neuroprotective action and the mechanisms of NES on retinal disorders.MethodsBased on the PRISMA guideline, a systematic review was conducted in PubMed, Web of Science, Embase, Scopus and Cochrane Library to collect all relevant in vivo studies on “the role of NES on retinal diseases” published up until September 2023. Possible biases were identified with the adopted SYRCLE’s tool.ResultsOf the 791 initially gathered studies, 21 articles met inclusion/exclusion criteria for full-text review. The results revealed the neuroprotective effect of NES (involved whole-eye, transcorneal, transscleral, transpalpebral, transorbital electrical stimulation) on different retinal diseases, including retinitis pigmentosa, retinal degeneration, high-intraocular pressure injury, traumatic optic neuropathy, nonarteritic ischemic optic neuropathy. NES could effectively delay degeneration and apoptosis of retinal neurons, preserve retinal structure and visual function with high security, and its mechanism of action might be related to promoting the secretion of neurotrophins and growth factors, decreasing inflammation, inhibiting apoptosis. The quality scores of included studies ranged from 5 to 8 points (a total of 10 points), according to SYRCLE’s risk of bias tool.ConclusionThis systematic review indicated that NES exerts neuroprotective effects on retinal disease models mainly through its neurotrophic, anti-inflammatory, and anti-apoptotic capabilities. To assess the efficacy of NES in a therapeutic setting, however, well-designed clinical trials are required in the future.
LIPCAR levels in plasma-derived extracellular vesicles is associated with left ventricle remodeling post-myocardial infarction
Authors: Turkieh Annie , Beseme Olivia , Saura Ouriel , Charrier Henri , Michel Jean-Baptiste , Amouyel Philippe , Thum Thomas , Bauters Christophe , Pinet Florence 
Published: January 2024

Abstract
Background
Long Intergenic noncoding RNA predicting CARdiac remodeling (LIPCAR) is a long noncoding RNA identified in plasma of patients after myocardial infarction (MI) to be associated with left ventricle remodeling (LVR). LIPCAR was also shown to be a predictor of early death in heart failure (HF) patients. However, no information regarding the expression of LIPCAR and its function in heart as well as the mechanisms involved in its transport to the circulation is known. The aims of this study are (1) to characterize the transporter of LIPCAR from heart to circulation; (2) to determine whether LIPCAR levels in plasma isolated-extracellular vesicles (EVs) reflect the alteration of its expression in total plasma and could be used as biomarkers of LVR post-MI.

Methods
Since expression of LIPCAR is restricted to human species and the limitation of availability of cardiac biopsy samples, serum-free conditioned culture media from HeLa cells were first used to characterize the extracellular transporter of LIPCAR before validation in EVs isolated from human cardiac biopsies (non-failing and ischemic HF patients) and plasma samples (patients who develop or not LVR post-MI). Differential centrifugation at 20,000g and 100,000g were performed to isolate the large (lEVs) and small EVs (sEVs), respectively. Western blot and nanoparticle tracking (NTA) analysis were used to characterize the isolated EVs. qRT-PCR analysis was used to quantify LIPCAR in all samples.

Results
We showed that LIPCAR is present in both lEVs and sEVs isolated from all samples. The levels of LIPCAR are higher in lEVs compared to sEVs isolated from HeLa conditioned culture media and cardiac biopsies. No difference of LIPCAR expression was observed in tissue or EVs isolated from cardiac biopsies obtained from ischemic HF patients compared to non-failing patients. Interestingly, LIPCAR levels were increased in lEVs and sEVs isolated from MI patients who develop LVR compared to patients who did not develop LVR.

Conclusion
Our data showed that large EVs are the main extracellular vesicle transporter of LIPCAR from heart into the circulation independently of the status, non-failing or HF, in patients. The levels of LIPCAR in EVs isolated from plasma could be used as biomarkers of LVR in post-MI patients.
Myeloid leukemia-derived galectin-1 downregulates CAR expression to hinder cytotoxicity of CAR T cells
Authors: Li Chuo , Zuo Shiyu , Shan Lingling , Huang Huifang , Cui Haidong , Feng Xiaoming 
Published: January 2024

Abstract
Background
Chimeric antigen receptor (CAR) T cells have shown significant activity in B-lineage malignancies. However, their efficacy in myeloid leukemia has not been successful due to unclear molecular mechanisms.

Methods
We conducted in vitro and in vivo experiments to investigate whether myeloid leukemia cells directly induce CAR down-regulation. Furthermore, we designed a CD33 CARKR in which all lysines in the cytoplasmic domain of CAR were mutated to arginine and verified through in vitro experiments that it could reduce the down-regulation of surface CARs and enhance the killing ability. Transcriptome sequencing was performed on various AML and ALL cell lines and primary samples, and the galectin-1-specific inhibitory peptide (anginex) successfully rescued the killing defect and T-cell activation in in vitro assays.

Results
CAR down-regulation induced by myeloid leukemia cells under conditions of low effector-to-tumor ratio, which in turn impairs the cytotoxicity of CAR T cells. In contrast, lysosomal degradation or actin polymerization inhibitors can effectively alleviate CAR down-regulation and restore CAR T cell-mediated anti-tumor functions. In addition, this study identified galectin-1 as a critical factor used by myeloid leukemia cells to induce CAR down-regulation, resulting in impaired T-cell activation.

Conclusion
The discovery of the role of galectin-1 in cell surface CAR down-regulation provides important insights for developing strategies to restore anti-tumor functions.
Predicting quetiapine dose in patients with depression using machine learning techniques based on real-world evidence
Authors: Hao Yupei , Zhang Jinyuan , Yu Jing , Yu Ze , Yang Lin , Hao Xin , Gao Fei , Zhou Chunhua 
Published: January 2024

Abstract
Background
Being one of the most widespread, pervasive, and troublesome illnesses in the world, depression causes dysfunction in various spheres of individual and social life. Regrettably, despite obtaining evidence-based antidepressant medication, up to 70% of people are going to continue to experience troublesome symptoms. Quetiapine, as one of the most commonly prescribed antipsychotic medication worldwide, has been reported as an effective augmentation strategy to antidepressants. The right quetiapine dose and personalized quetiapine treatment are frequently challenging for clinicians. This study aimed to identify important influencing variables for quetiapine dose by maximizing the use of data from real world, and develop a predictive model of quetiapine dose through machine learning techniques to support selections for treatment regimens.

Methods
The study comprised 308 depressed patients who were medicated with quetiapine and hospitalized in the First Hospital of Hebei Medical University, from November 1, 2019, to August 31, 2022. To identify the important variables influencing the dose of quetiapine, a univariate analysis was applied. The prediction abilities of nine machine learning models (XGBoost, LightGBM, RF, GBDT, SVM, LR, ANN, DT) were compared. Algorithm with the optimal model performance was chosen to develop the prediction model.

Results
Four predictors were selected from 38 variables by the univariate analysis (p < 0.05), including quetiapine TDM value, age, mean corpuscular hemoglobin concentration, and total bile acid. Ultimately, the XGBoost algorithm was used to create a prediction model for quetiapine dose that had the greatest predictive performance (accuracy = 0.69) out of nine models. In the testing cohort (62 cases), a total of 43 cases were correctly predicted of the quetiapine dose regimen. In dose subgroup analysis, AUROC for patients with daily dose of 100 mg, 200 mg, 300 mg and 400 mg were 0.99, 0.75, 0.93 and 0.86, respectively.

Conclusions
In this work, machine learning techniques are used for the first time to estimate the dose of quetiapine for patients with depression, which is valuable for the clinical drug recommendations.
Cutaneous melanocytic tumor with CRTC1::TRIM11 fusion: a case report
Authors: Duan Rong , He Xiaojuan , Ma Xiaojing , Huang Fengbo , Hu Xiangrong 
Published: January 2024

Abstract
Background
Cutaneous Melanocytic Tumor with CRTC1::TRIM11 Fusion (CMTCT) represents a novel and rare entity in the realm of dermatological oncology, characterized by distinct melanocytic differentiation. This particular tumor type has yet to be officially recognized by the World Health Organization (WHO). CMTCT is generally perceived as a tumor with a relatively indolent nature; however, it is not devoid of metastatic potential. Therefore, ensuring complete surgical excision of the tumor, coupled with rigorous long-term follow-up, is paramount for patient management. In this context, we report the case of an 18-year-old female patient who presented with a dull red nodule on her left leg. Initial surgical intervention led to a pathological diagnosis of CMTCT, but it was determined that the tumor had not been fully excised. Consequently, a second surgical procedure was undertaken to achieve complete removal of the tumor. During a follow-up period of six months post-surgery, the patient showed no signs of local recurrence or metastasis, indicating a successful outcome.

Case presentation
An 18-year-old female patient noticed a dull red nodule on her left leg three years ago, which exhibited slow growth over time. She underwent a subcutaneous tumor resection. Histological examination under high-power magnification revealed that the neoplasm consisted of epithelioid cells arranged in nests, fascicles, bundles, or sheets. The tumor cells had round or ovoid nuclei with prominent nucleoli and visible mitotic figures. Notably, areas resembling nevus cell clusters were observed. Immunohistochemical analysis confirmed melanocytic differentiation. Next-generation sequencing (NGS) identified a CRTC1::TRIM11 fusion, and fluorescence in situ hybridization (FISH) for CRTC1 confirmed rearrangement. Consequently, a diagnosis of cutaneous melanocytic tumor with CRTC1::TRIM11 fusion was established.

Conclusions
CMTCT is a rare tumor characterized by melanocytic differentiation. In this case, the tumor predominantly comprised epithelioid cells with localized nevus cell clusters. The expression of melanocyte markers could easily lead to a misdiagnosis as cutaneous melanoma. However, several distinguishing features were noted: the tumor was not connected to the epidermis, exhibited low cellular heterogeneity and proliferation index, and showed minimal cellular atypia. Additionally, tests for EWSR1 rearrangement (FISH) and BRAF V600E mutation (PCR-ARMS) were negative.This case underscores the importance of a comprehensive diagnostic approach when clinical, microscopic, immunohistochemical, and molecular findings do not align. The presence of nevus cell clusters morphology in the tumor cells enhances our understanding of this disease’s histological spectrum and aids in avoiding misdiagnosis or missed diagnosis.
Compressive buttress compared with off-axial screw fixation for vertical femoral neck fractures in young adults: a prospective, randomized controlled trial
Authors: Yin Bo-hao , Liu Chen-jun , Sherrier Matthew C. , Sun Hui , Zhang Wei 
Published: January 2024

Abstract
Background
To compare the clinical outcomes of compressive buttress screw (CBS) fixation, a novel screw fixation strategy, to off-axial screw fixation (off-axial partial threaded cannulated screw, OPTCS) for vertical femoral neck fractures (FNFs) in young adults.

Methods
A total of 146 adults younger than 55 years old with high-energy Pauwels type III FNFs were randomized to receive CBS fixation or OPTCS fixation. Primary outcomes were complication rates, including fixation failure, fracture nonunion, and avascular necrosis of the femoral head (ANFH) at 24 months after treatment. Fixation loosening, femoral neck shortening and varus collapse, patient function and quality of life using the Harris hip score (HHS), and EuroQol-5 dimensional-5 levels (EQ-5D-5L) questionnaire (including EQ-5D-5L and EQ-VAS) were assessed as secondary outcomes at 24 months.

Results
CBS and OPTCS fixation groups were similar with regard to demographics at baseline. At 24 months, patients in the CBS fixation cohort had a significantly lower rate of fixation failure (10.5% vs. 25.0%, p = 0.041) and fracture nonunion (1.8% vs. 18.3%, p = 0.003) compared with patients who received OPTCS fixation. There was no difference in rate of ANFH (7.0% vs. 11.7%, p = 0.389) between groups. Additionally, patients managed with CBS fixation showed significantly less fixation loosening (19.3% vs. 58.3%, p < 0.001), less severe femoral neck shortening and varus collapse (10.5% vs. 25.0%, p = 0.007), higher HHS (93 vs. 83, p = 0.001) and more excellent grade (68.4% vs. 36.7%, p = 0.008), higher EQ-5D-5L (0.814 vs, 0.581, p < 0.001) and EQ-VAS (85 vs. 80, p = 0.002).

Conclusion
CBS screw fixation confers significantly lower complication rate in addition to higher functional and quality of life outcomes for young adults with high-energy FNF compared with OPTCS fixation.

Trial registration
This prospective, randomized controlled trial was approved by the institutional review board of our center, Ethics Committee of Shanghai sixth people's Hospital, and registered at www.chictr.org.cn (Approval Number: ChiCTR1900026283; Registered 29 September 2019—Retrospectively registered, https://www.chictr.org.cn/showproj.html?proj=43164).
Placement of stent grafts with different calibers into the true and false lumens of anastomotic aneurysms after descending aortic replacement for aortic dissection
Authors: Uehara Hiroo , Uchiyama Masateru , Imazuru Tomohiro 
Published: January 2024

AbstractAnastomotic aneurysms present as a life-threatening emergency after descending aortic replacement for aortic dissection. Thoracic endovascular aneurysm repair (TEVAR) has been performed since the early 2000s for complicated cases in which re-thoracotomy cannot be adopted. We report the case of a 57-year-old male patient, during a 5-year follow-up after descending aortic replacement for aortic dissection, developed aneurysm expansion around the false lumen on the peripheral side of the artificial graft. Considering the risk and the patient’s desires, we opted to perform TEVAR with different calibers into the true and false lumens “modified kissing stents technique”. His postoperative course was uneventful without any complications. This case highlights the utility of the modified kissing stents technique for anastomotic aneurysms after descending aortic replacement for aortic dissection using stent grafts with different calibers into the true and false lumens.