bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early discharge hospital at home as alternative to routine hospital care for older people: a systematic review and meta-analysis
Authors: Lin Lulu , Cheng Mengyuan , Guo Yawei , Cao Xiaowen , Tang Weiming , Xu Xin , Cheng Weibin , Xu Zhongzhi 
Published: June 2024

Abstract
Background
The global population of adults aged 60 and above surpassed 1 billion in 2020, constituting 13.5% of the global populace. Projections indicate a rise to 2.1 billion by 2050. While Hospital-at-Home (HaH) programs have emerged as a promising alternative to traditional routine hospital care, showing initial benefits in metrics such as lower mortality rates, reduced readmission rates, shorter treatment durations, and improved mental and functional status among older individuals, the robustness and magnitude of these effects relative to conventional hospital settings call for further validation through a comprehensive meta-analysis.

Methods
A comprehensive literature search was executed during April–June 2023, across PubMed, MEDLINE, Embase, Web of Science, and Cumulative Index of Nursing and Allied Health Literature (CINAHL) to include both RCT and non-RCT HaH studies. Statistical analyses were conducted using Review Manager (version 5.4), with Forest plots and I2 statistics employed to detect inter-study heterogeneity. For I2 > 50%, indicative of substantial heterogeneity among the included studies, we employed the random-effects model to account for the variability. For I2 ≤ 50%, we used the fixed effects model. Subgroup analyses were conducted in patients with different health conditions, including cancer, acute medical conditions, chronic medical conditions, orthopedic issues, and medically complex conditions.

Results
Fifteen trials were included in this systematic review, including 7 RCTs and 8 non-RCTs. Outcome measures include mortality, readmission rates, treatment duration, functional status (measured by the Barthel index), and mental status (measured by MMSE). Results suggest that early discharge HaH is linked to decreased mortality, albeit supported by low-certainty evidence across 13 studies. It also shortens the length of treatment, corroborated by seven trials. However, its impact on readmission rates and mental status remains inconclusive, supported by nine and two trials respectively. Functional status, gauged by the Barthel index, indicated potential decline with early discharge HaH, according to four trials. Subgroup analyses reveal similar trends.

Conclusions
While early discharge HaH shows promise in specific metrics like mortality and treatment duration, its utility is ambiguous in the contexts of readmission, mental status, and functional status, necessitating cautious interpretation of findings.
Association between exercise habits and incident type 2 diabetes mellitus in patients with thyroid cancer: nationwide population-based study
Authors: Park Jiyun , Jung Jin-Hyung , Park Hyunju , Song Young Shin , Kim Soo-Kyung , Cho Yong-Wook , Han Kyungdo , Kim Kyung-Soo 
Published: June 2024

Abstract
Background
We investigated the association between exercise habits before or after thyroidectomy and incident type 2 diabetes mellitus (T2DM) in patients with thyroid cancer.

Methods
An observational cohort study of 69,526 thyroid cancer patients who underwent thyroidectomy for the treatment of thyroid cancer between 2010 and 2016 was performed using the Korean National Health Information Database. Regular exercise was defined as mid-term or vigorous exercise at least 1 day in a week based on a self-reported questionnaire. Patients were divided into four groups according to exercise habits before and after thyroidectomy: persistent non-exercisers, new exercisers, exercise dropouts, and exercise maintainers.

Results
During a median follow-up of 4.5 years, 2,720 (3.91%) patients developed T2DM. The incidence of T2DM per 1,000 person years was lower in patients who performed regular exercise before or after thyroidectomy than in persistent non-exercisers (10.77 in persistent non-exerciser group, 8.28 in new exerciser group, 8.59 in exercise dropout group, and 7.61 in exercise maintainer group). Compared with the persistent non-exerciser group, the new exerciser group (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.78–0.97), the exercise dropout group (HR 0.81, 95% CI 0.72–0.91), and the exercise maintainer group (HR 0.84, 95% CI 0.76–0.93) had lower risks of incident T2DM. Exercising < 1,500 MET-minutes/week in the exercise maintainer group was associated with a lower risk of incident T2DM compared with persistent non-exercisers (< 500: HR 0.80, 95% CI 0.67–0.96, P = 0.002; 500 to < 1,000: HR 0.81, 95% CI 0.71–0.93, P < 0.001; 1,000 to < 1,500: HR 0.81, 95% CI 0.69–0.94, P < 0.001).

Conclusions
Regular exercise before or after thyroidectomy was associated with a lower risk of incident T2DM in patients with thyroid cancer.

Graphical Abstract
Taxane combined with lobaplatin or anthracycline for neoadjuvant chemotherapy of triple-negative breast cancer: a randomized, controlled, phase II study
Authors: Wang Cheng , Yuan Long , Wu Xiujuan , Wang Yan , Tian Hao , Zhang Guozhi , Wan Andi , Xiong Siyi , Wang Chengfang , Zhou Yuqin , Ma Dandan , Bao Yangqiu , Qu Man , Jiang Jun , Zhang Yi , Qi Xiaowei 
Published: June 2024

Abstract
Background
Previous studies have shown that the addition of platinum to neoadjuvant chemotherapy (NAC) improved outcomes for patients with triple-negative breast cancer (TNBC). However, no studies have assessed the efficacy and safety of the combination of taxane and lobaplatin. In this study, we conducted a randomized controlled phase II clinical study to compare the efficacy and safety of taxane combined with lobaplatin or anthracycline.

Methods
We randomly allocated patients with stage I–III TNBC into Arm A and Arm B. Arm A received six cycles of taxane combined with lobaplatin (TL). Arm B received six cycles of taxane combined with anthracycline and cyclophosphamide (TEC) or eight cycles of anthracycline combined with cyclophosphamide and sequential use of taxane (EC-T). Both Arms underwent surgery after NAC. The primary endpoint was the pathologic complete response (pCR). Secondary endpoints were event-free survival (EFS), overall survival (OS), and safety.

Results
A total of 103 patients (51 in Arm A and 52 in Arm B) were assessed. The pCR rate of Arm A was significantly higher than that of Arm B (41.2% vs. 21.2%, P = 0.028). Patients with positive lymph nodes and low neutrophil-to-lymphocyte ratio (NLR) benefited significantly more from Arm A than those with negative lymph nodes and high NLR (Pinteraction = 0.001, Pinteraction = 0.012, respectively). There was no significant difference in EFS (P = 0.895) or OS (P = 0.633) between the two arms. The prevalence of grade-3/4 anemia was higher in Arm A (P = 0.015), and the prevalence of grade-3/4 neutropenia was higher in Arm B (P = 0.044).

Conclusions
Neoadjuvant taxane plus lobaplatin has shown better efficacy than taxane plus anthracycline, and both regimens have similar toxicity profiles. This trial may provide a reference for a better combination strategy of immunotherapy in NAC for TNBC in the future.
Evidence for a relationship between genetic polymorphisms of the L-DOPA transporter LAT2/4F2hc and risk of hypertension in the context of chronic kidney disease
Authors: Crocco Paolina , Dato Serena , La Grotta Rossella , Passarino Giuseppe , Rose Giuseppina 
Published: June 2024

Abstract
Background
Chronic kidney disease (CKD) and hypertension are chronic diseases affecting a large portion of the population frequently coexistent and interdependent. The inability to produce/use adequate renal dopamine may contribute to the development of hypertension and renal dysfunction. The heterodimeric amino acid transporter LAT2/4F2hc (SLC7A8/SLC3A2 genes) promotes the uptake of L-DOPA, the natural precursor of dopamine. We examined the plausibility that SLC7A8/SLC3A2 gene polymorphisms may contribute to hypertensive CKD by affecting the L-DOPA uptake.

Methods
421 subjects (203 men and 218 women, mean age of 78.9 ± 9.6 years) were recruited and divided in four groups according to presence/absence of CKD, defined as reduced estimated glomerular filtration rate (eGFR < 60 ml/min/m2) calculated using the creatinine-based Berlin Initiative Study–1 (BIS1) equation, and to presence/absence of hypertension (systolic blood pressure ≥ 140 and/or diastolic blood pressure ≥ 90 mmHg). Subjects were analysed for selected SNPs spanning the SLC7A8 and SLC3A2 loci by Sequenom MassARRAY iPLEX platform.

Results
The most significant SNP at the SLC3A2 (4F2hc) locus was rs2282477-T/C, with carriers of the C-allele having a lower chance to develop hypertension among CKD affected individuals [OR = 0.33 (CI 0.14–0.82); p = 0.016]. A similar association with hypertensive CKD was found for the SLC7A8 (LAT2) rs3783436-T/C, whose C-allele resulted associated with decreased risk of hypertension among subjects affected by CKD [OR = 0.56 (95% CI 0.35–0.90; p = 0.017]. The two variants were predicted to be potentially functional.

Conclusions
The association between SLC3A2 and SLC7A8 variants to hypertension development in patients with renal failure could be linked to changes in L-DOPA uptake and consequently dopamine synthesis. Although the associations do not survive correction for Bonferroni multiple testing, and additional research is needed, our study opens new avenues for future basic and translational research in the field of hypertensive CKD.
Acute-to-chronic glycemic ratio as an outcome predictor in ischemic stroke in patients with and without diabetes mellitus
Authors: Climent Elisenda , Rodriguez-Campello Ana , Jiménez-Balado Joan , Fernández-Miró Mercè , Jiménez-Conde Jordi , Llauradó Gemma , Ois Ángel , Flores Juana A. , Cuadrado-Godia Elisa , Steinhauer Eva Giralt , Chillarón Juan J. ,   Neurovascular Research Group (NEUVAS), Perez Isabel Fernandez , Gomez Adrià Macías , Perez Antoni Suarez , Alonso Daniel Guisado , Prats Marta Vallverdú 
Published: June 2024

Abstract
Objective
Elevated plasma glucose levels are common in patients suffering acute ischemic stroke (AIS), and acute hyperglycemia has been defined as an independent determinant of adverse outcomes. The impact of acute-to-chronic glycemic ratio (ACR) has been analyzed in other diseases, but its impact on AIS prognosis remains unclear. The main aim of this study was to assess whether the ACR was associated with a 3-month poor prognosis in patients with AIS.

Research, design and methods
Retrospective analysis of patients admitted for AIS in Hospital del Mar, Barcelona. To estimate the chronic glucose levels (CGL) we used the formula eCGL= [28.7xHbA1c (%)]-46.7. The ACR (glycemic at admission / eCGL) was calculated for all subjects. Tertile 1 was defined as: 0.28–0.92, tertile 2: 0.92–1.13 and tertile 3: > 1.13. Poor prognosis at 3 months after stroke was defined as mRS score 3–6.

Results
2.774 subjects with AIS diagnosis were included. Age, presence of diabetes, previous disability (mRS), initial severity (NIHSS) and revascularization therapy were associated with poor prognosis (p values < 0.05). For each 0.1 increase in ACR, there was a 7% increase in the risk of presenting a poor outcome. The 3rd ACR tertile was independently associated with a poor prognosis and mortality. In the ROC curves, adding the ACR variable to the classical clinical model did not increase the prediction of AIS prognosis (0.786 vs. 0.781).

Conclusions
ACR was positively associated with a poor prognosis and mortality at 3-months follow-up after AIS. Subjects included in the 3rd ACR tertile presented a higher risk of poor prognosis and mortality. Baseline glucose or ACR did not add predictive value in comparison to only using classical clinical variables.
Integrated profiling identifies DXS253E as a potential prognostic marker in colorectal cancer
Authors: Xing Pu , Hao Hao , Chen Jiangbo , Qiao Xiaowen , Song Tongkun , Yang Xinying , Weng Kai , Hou Yifan , Chen Jie , Wang Zaozao , Di Jiabo , Jiang Beihai , Xing Jiadi , Su Xiangqian 
Published: June 2024

Abstract
Background
Increasing evidence suggests that DXS253E is critical for cancer development and progression, but the function and potential mechanism of DXS253E in colorectal cancer (CRC) remain largely unknown. In this study, we evaluated the clinical significance and explored the underlying mechanism of DXS253E in CRC.

Methods
DXS253E expression in cancer tissues was investigated using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The Kaplan-Meier plot was used to assess the prognosis of DXS253E. The cBioPortal, MethSurv, and Tumor Immune Estimation Resource (TIMER) databases were employed to analyze the mutation profile, methylation, and immune infiltration associated with DXS253E. The biological functions of DXS253E in CRC cells were determined by CCK-8 assay, plate cloning assay, Transwell assay, flow cytometry, lactate assay, western blot, and qRT-PCR.

Results
DXS253E was upregulated in CRC tissues and high DXS253E expression levels were correlated with poor survival in CRC patients. Our bioinformatics analyses showed that high DXS253E gene methylation levels were associated with the favorable prognosis of CRC patients. Furthermore, DXS253E levels were linked to the expression levels of several immunomodulatory genes and an abundance of immune cells. Mechanistically, the overexpression of DXS253E enhanced proliferation, migration, invasion, and the aerobic glycolysis of CRC cells through the AKT/mTOR pathway.

Conclusions
We demonstrated that DXS253E functions as a potential role in CRC progression and may serve as an indicator of outcomes and a therapeutic target for regulating the AKT/mTOR pathway in CRC.
Circ6834 suppresses non-small cell lung cancer progression by destabilizing ANHAK and regulating miR-873-5p/TXNIP axis
Authors: Wang Maoye , Ding Xiaoge , Fang Xinjian , Xu Jing , Chen Yanke , Qian Yu , Zhang Jiahui , Yu Dan , Zhang Xiaoxin , Ma Xiuqin , Zhu Taofeng , Gu Jianmei , Zhang Xu 
Published: June 2024

AbstractBackgroundCircular RNAs (circRNAs) play important roles in cancer progression and metastasis. However, the expression profiles and biological roles of circRNAs in non-small cell lung cancer (NSCLC) remain unclear.MethodsIn this study, we identified a novel circRNA, hsa_circ_0006834 (termed circ6834), in NSCLC by RNA-seq and investigated the biological role of circ6834 in NSCLC progression in vitro and in vivo. Finally, the molecular mechanism of circ6834 was revealed by tagged RNA affinity purification (TRAP), western blot, RNA immunoprecipitation, dual luciferase reporter gene assays and rescue experiments.ResultsOur results showed that circ6834 was downregulated in NSCLC tumor tissues and cell lines. Circ6834 overexpression inhibited NSCLC cell growth and metastasis both in vitro and in vivo, while circ6834 knockdown had the opposite effect. We found that TGF-β treatment decreased circ6834 expression, which was associated with the QKI reduction in NSCLC cells and circ6834 antagonized TGF-β-induced EMT and metastasis in NSCLC cells. Mechanistically, circ6834 bound to AHNAK protein, a key regulator of TGF-β/Smad signaling, and inhibited its stability by enhancing TRIM25-mediated ubiquitination and degradation. In addition, circ6834 acted as a miRNA sponge for miR-873-5p and upregulated TXNIP gene expression, which together inactivated the TGF-β/Smad signaling pathway in NSCLC cells.ConclusionIn conclusion, circ6834 is a tumor-suppressive circRNA that inhibits NSCLC progression by forming a negative regulatory feedback loop with the TGF-β/Smad signaling pathway and represents a novel therapeutic target for NSCLC.
Targeting SUMOylation with an injectable nanocomposite hydrogel to optimize radiofrequency ablation therapy for hepatocellular carcinoma
Authors: Liu Junfeng , Li Xi , Chen Jiawen , Guo Jingpei , Guo Hui , Zhang Xiaoting , Fan Jinming , Zhang Ke , Mao Junjie , Zhou Bin 
Published: June 2024

Abstract
Background
Incomplete radiofrequency ablation (iRFA) in hepatocellular carcinoma (HCC) often leads to local recurrence and distant metastasis of the residual tumor. This is closely linked to the development of a tumor immunosuppressive environment (TIME). In this study, underlying mechanisms and potential therapeutic targets involved in the formation of TIME in residual tumors following iRFA were explored. Then, TAK-981-loaded nanocomposite hydrogel was constructed, and its therapeutic effects on residual tumors were investigated.

Results
This study reveals that the upregulation of small ubiquitin-like modifier 2 (Sumo2) and activated SUMOylation is intricately tied to immunosuppression in residual tumors post-iRFA. Both knockdown of Sumo2 and inhibiting SUMOylation with TAK-981 activate IFN-1 signaling in HCC cells, thereby promoting dendritic cell maturation. Herein, we propose an injectable PDLLA-PEG-PDLLA (PLEL) nanocomposite hydrogel which incorporates self-assembled TAK-981 and BSA nanoparticles for complementary localized treatment of residual tumor after iRFA. The sustained release of TAK-981 from this hydrogel curbs the expansion of residual tumors and notably stimulates the dendritic cell and cytotoxic lymphocyte-mediated antitumor immune response in residual tumors while maintaining biosafety. Furthermore, the treatment with TAK-981 nanocomposite hydrogel resulted in a widespread elevation in PD-L1 levels. Combining TAK-981 nanocomposite hydrogel with PD-L1 blockade therapy synergistically eradicates residual tumors and suppresses distant tumors.

Conclusions
These findings underscore the potential of the TAK-981-based strategy as an effective therapy to enhance RFA therapy for HCC.

Graphic Abstract
Exosomes as drug delivery systems in glioma immunotherapy
Authors: Hao Xinqing , Wang Shiming , Wang Liang , Li Jiaqi , Li Ying , Liu Jing 
Published: June 2024

AbstractRecently, the significant benefits of cancer immunotherapy for most cancers have been demonstrated in clinical and preclinical studies. However, the efficacy of these immunotherapies for gliomas is limited, owing to restricted drug delivery and insufficient immune activation. As drug carriers, exosomes offer the advantages of low toxicity, good biocompatibility, and intrinsic cell targeting, which could enhance glioma immunotherapy efficacy. However, a review of exosome-based drug delivery systems for glioma immunotherapy has not been presented. This review introduces the current problems in glioma immunotherapy and the role of exosomes in addressing these issues. Meanwhile, preparation and application strategies of exosome-based drug delivery systems for glioma immunotherapy are discussed, especially for enhancing immunogenicity and reversing the immunosuppressive tumor microenvironment. Finally, we briefly describe the challenges of exosome-based drug delivery systems in clinical translation. We anticipate that this review will guide the use of exosomes as drug carriers for glioma immunotherapy.
Graphical Abstract
Single-cell RNA transcriptomic reveal the mechanism of MSC derived small extracellular vesicles against DKD fibrosis
Authors: Ji Cheng , Zhang Jiahui , Shi Hui , Chen Binghai , Xu Wenrong , Jin Jianhua , Qian Hui 
Published: June 2024

AbstractDiabetic kidney disease (DKD), a chronic kidney disease, is characterized by progressive fibrosis caused due to persistent hyperglycemia. The development of fibrosis in DKD determines the patient prognosis, but no particularly effective treatment. Here, small extracellular vesicles derived from mesenchymal stem cells (MSC-sEV) have been used to treat DKD fibrosis. Single-cell RNA sequencing was used to analyze 27,424 cells of the kidney, we have found that a novel fibrosis-associated TGF-β1+Arg1+macrophage subpopulation, which expanded and polarized in DKD and was noted to be profibrogenic. Additionally, Actin+Col4a5+mesangial cells in DKD differentiated into myofibroblasts. Multilineage ligand-receptor and cell-communication analysis showed that fibrosis-associated macrophages activated the TGF-β1/Smad2/3/YAP signal axis, which promotes mesangial fibrosis-like change and accelerates renal fibrosis niche. Subsequently, the transcriptome sequencing and LC-MS/MS analysis indicated that MSC-sEV intervention could restore the levels of the kinase ubiquitin system in DKD and attenuate renal interstitial fibrosis via delivering CK1δ/β-TRCP to mediate YAP ubiquitination degradation in mesangial cells. Our findings demonstrate the unique cellular and molecular mechanisms of MSC-sEV in treating the DKD fibrosis niche at a single-cell level and provide a novel therapeutic strategy for renal fibrosis.
3D stem-like spheroids-on-a-chip for personalized combinatorial drug testing in oral cancer
Authors: Mehta Viraj , Vilikkathala Sudhakaran Sukanya , Nellore Vijaykumar , Madduri Srinivas , Rath Subha Narayan 
Published: June 2024

Abstract
Background
Functional drug testing (FDT) with patient-derived tumor cells in microfluidic devices is gaining popularity. However, the majority of previously reported microfluidic devices for FDT were limited by at least one of these factors: lengthy fabrication procedures, absence of tumor progenitor cells, lack of clinical correlation, and mono-drug therapy testing. Furthermore, personalized microfluidic models based on spheroids derived from oral cancer patients remain to be thoroughly validated. Overcoming the limitations, we develop 3D printed mold-based, dynamic, and personalized oral stem-like spheroids-on-a-chip, featuring unique serpentine loops and flat-bottom microwells arrangement.

Results
This unique arrangement enables the screening of seven combinations of three drugs on chemoresistive cancer stem-like cells. Oral cancer patients-derived stem-like spheroids (CD 44+) remains highly viable (> 90%) for 5 days. Treatment with a well-known oral cancer chemotherapy regimen (paclitaxel, 5 fluorouracil, and cisplatin) at clinically relevant dosages results in heterogeneous drug responses in spheroids. These spheroids are derived from three oral cancer patients, each diagnosed with either well-differentiated or moderately-differentiated squamous cell carcinoma. Oral spheroids exhibit dissimilar morphology, size, and oral tumor-relevant oxygen levels (< 5% O2). These features correlate with the drug responses and clinical diagnosis from each patient’s histopathological report.

Conclusions
Overall, we demonstrate the influence of tumor differentiation status on treatment responses, which has been rarely carried out in the previous reports. To the best of our knowledge, this is the first report demonstrating extensive work on development of microfluidic based oral cancer spheroid model for personalized combinatorial drug screening. Furthermore, the obtained clinical correlation of drug screening data represents a significant advancement over previously reported personalized spheroid-based microfluidic devices. Finally, the maintenance of patient-derived spheroids with high viability under oral cancer relevant oxygen levels of less than 5% O2 is a more realistic representation of solid tumor microenvironment in our developed device.

Graphical Abstract