bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the role of cellular senescence in cancer prognosis across multiple tumor types
Authors: Xu Qi , Feng Xiaoying 
Published: July 2024

BackgroundCellular senescence is a common biological process with a well-established link to cancer. However, the impact of cellular senescence on tumor progression remains unclear. To investigate this relationship, we utilized transcriptomic data from a senescence gene set to explore the connection between senescence and cancer prognosis.MethodsWe developed the senescence score by the Least Absolute Shrinkage and Selection Operator (LASSO) Cox model. We obtained transcriptomic information of the senescence gene set from The Cancer Genome Atlas (TCGA) program. Additionally, we created a nomogram that integrates these senescence scores with clinical characteristics, providing a more comprehensive tool for prognosis evaluation.ResultsWe calculated the senescence score based on the expression level of 42 senescence-related genes. We established the nomogram based on the senescence score and clinical characteristics. The senescence score showed a positive correlation with epithelial-to-mesenchymal transition, cell cycle, and glycolysis, and a negative correlation with autophagy. Furthermore, we carried out Gene Ontology (GO) analysis to explore the signaling pathways and biological process in different senescence score groups.ConclusionsThe senescence score, a novel tool constructed in this study, shows promise in predicting survival outcomes across various cancer types. These findings not only highlight the complex interplay between senescence and cancer but also indicate that cellular senescence might serve as a biomarker for tumor prognosis.
Mendelian randomization study and mediation analysis about the relation of inflammatory bowel disease and diabetic retinopathy: the further exploration of gut-retina axis
Authors: Lin Jiayi , Cheng Yaqi , Gu Simin , Song Siqi , Zhang Huini , Li Jianbing , Ling Shiqi 
Published: July 2024

BackgroundThe concept of the gut-retinal axis proposed by previous scholars primarily focused on the relationship between intestinal microbiota and retinal diseases, and few further expanded the relationship between intestinal diseases and retinal diseases. To further substantiate the concept of the gut-retinal axis, we analyzed inflammatory bowel disease (IBD) and diabetic retinopathy (DR) using Mendelian randomization (MR), and use mediation analysis to further explore the potential substances that influence this causal relationship.MethodsThe genome-wide association study’s (GWAS) summary statistics for genetic variations were utilized in a Mendelian randomization (MR) investigation. GWAS data on IBD (including ulcerative colitis (UC), Crohn’s disease (CD), and IBD) for non-Finnish Europeans (NFE) were sourced from published articles. In contrast, data on DR (including DR and diabetic maculopathy (DMP)) were obtained from FinnGen R9. The causal relationship has been investigated using inverse variance weighted (IVW), MR-Egger, and weighted median and sensitivity analysis was applied to verify the stability of the results. In addition, we applied mediation analysis to investigate whether circulating inflammatory proteins and plasma lipids played a mediating role, and calculated its effect ratio.ResultsThe causal relationship between IBD and DR was discovered by employing the inverse variance weighted (IVW) method and weighted median method. In forward MR, UC was significantly associated with lower risk of DR (IVW: OR=0.874; 95%CI= 0.835–0.916; P value= 1.28E-08) (Weighted median: OR=0.893; 95%CI= 0.837–0.954; P value= 7.40E-04). In reverse MR, it was shown that DR (IVW: OR=0.870; 95%CI= 0.828–0.914; P value= 2.79E-08)(Weighted median: OR=0.857; 95%CI= 0.801–0.916; P value= 6.40E-06) and DMP (IVW: OR=0.900; 95%CI= 0.865–0.937; P value= 3.34E-07)(Weighted median: OR=0.882; 95%CI= 0.841–0.924; P value= 1.82E-07) could reduce the risk of CD. What’s more, DR is associated with a lower risk of IBD according to genetic prediction (IVW: OR=0.922; 95%CI= 0.873–0.972; P value= 0.002) (Weighted median: OR=0.924; 95%CI= 0.861–0.992; P value= 0.029). Fibroblast growth factor 21 (FGF21), phosphatidylcholine (PC), and triacylglycerol (TG) serve as mediators in these relationships.ConclusionsOur research offers novel insights and sources for investigating the gut-retina axis in the genetic relationship between IBD and DR. We discover four mediators and more about the association between the intestine and retinal disorders and provide more evidence for the gut-retinal axis theory.
Efficacy and safety of polyethylene glycol loxenatide in treating mild-to-moderate diabetic kidney disease in type 2 diabetes patients: a randomized, open-label, clinical trial
Authors: Cao YongSheng , Cao Shujie , Zhao Jiangang , Zhao Jianqin , Zhao Yanan , Liu Ying 
Published: July 2024

ObjectiveThis study aimed to evaluate the efficacy and safety of polyethylene glycol loxenatide (PEG-Loxe) compared to those of dapagliflozin in patients with mild-to-moderate diabetic kidney disease (DKD), a prevalent microvascular complication of type 2 diabetes mellitus (T2DM). The study is set against the backdrop of increasing global diabetes incidence and the need for effective DKD management.MethodsThis study constituted a single-center, randomized, open-label, clinical trial. The trial included patients with mild-to-moderate DKD and suboptimal glycemic control. Eligible participants were randomly allocated to one of the two groups for treatment with either PEG-Loxe or dapagliflozin. The primary endpoint was the change in UACR from baseline at 24 weeks.ResultsOverall, 106 patients were randomized and 80 patients completed the study. Following 24 weeks of treatment, the PEG-Loxe group exhibited a mean percent change in baseline UACR of −29.3% (95% confidence interval [CI]: −34.8, −23.7), compared to that of −31.8% in the dapagliflozin group (95% CI: −34.8, −23.7). Both PEG-Loxe and dapagliflozin showed similar efficacy in reducing UACR, with no significant difference between the groups (p = 0.336). The HbA1c levels decreased by −1.30% (95% CI: −1.43, −1.18) in the PEG-Loxe group and by −1.29% (95% CI: −1.42, −1.17) in the dapagliflozin group (p = 0.905). The TG levels decreased by −0.56 mmol/L (95% CI: −0.71, −0.42) in the PEG-Loxe group and −0.33 mmol/L (95% CI: −0.48, −0.19) in the dapagliflozin group (p = 0.023). Differences in TC, HDL-C, LDL-C, SBP, and DBP levels between the groups were not statistically significant (all p &gt; 0.05). Safety profiles were consistent with previous findings, with gastrointestinal adverse events being more common in the PEG-Loxe group.ConclusionsPEG-Loxe is as effective as dapagliflozin in improving urine protein levels in patients with mild-to-moderate DKD and offers superior benefits in improving lipid profiles. These findings support the use of PEG-Loxe in DKD management, contributing to evidence-based treatment options.Clinical Trial Registrationwww.chictr.org.cn, identifier ChiCTR2300070919.
Runtime support for CPU-GPU high-performance computing on distributed memory platforms
Authors: Thomadakis Polykarpos , Chrisochoides Nikos 
Published: July 2024

IntroductionHardware heterogeneity is here to stay for high-performance computing. Large-scale systems are currently equipped with multiple GPU accelerators per compute node and are expected to incorporate more specialized hardware. This shift in the computing ecosystem offers many opportunities for performance improvement; however, it also increases the complexity of programming for such architectures.MethodsThis work introduces a runtime framework that enables effortless programming for heterogeneous systems while efficiently utilizing hardware resources. The framework is integrated within a distributed and scalable runtime system to facilitate performance portability across heterogeneous nodes. Along with the design, this paper describes the implementation and optimizations performed, achieving up to 300% improvement on a single device and linear scalability on a node equipped with four GPUs.ResultsThe framework in a distributed memory environment offers portable abstractions that enable efficient inter-node communication among devices with varying capabilities. It delivers superior performance compared to MPI+CUDA by up to 20% for large messages while keeping the overheads for small messages within 10%. Furthermore, the results of our performance evaluation in a distributed Jacobi proxy application demonstrate that our software imposes minimal overhead and achieves a performance improvement of up to 40%.DiscussionThis is accomplished by the optimizations at the library level and by creating opportunities to leverage application-specific optimizations like over-decomposition.
Efficacy and safety of PD-1/L1 inhibitors as first-line therapy for metastatic colorectal cancer: a meta-analysis
Authors: Huang Zhilong , Li Chunyan , Huang Yanping , Liang Weiming , Tao Haiyun 
Published: July 2024

ObjectiveTo evaluate the efficacy and safety of PD-1/L1 inhibitors as first-line therapy in metastatic colorectal cancer(mCRC).MethodArticles evaluating first-line PD-1/L1 inhibitors for mCRC were sought in four databases (Pubmed, Embase, Web of Science, and the Cochrane Library) from the inception of the databases until 11 November 2023. Meta-analyses were conducted to assess the rates of progression-free survival (PFS), overall survival (OS), complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), objective response rate (ORR), disease control rate (DCR), and grade ≥ 3 treatment-related adverse events (trAEs).ResultsTotally nine studies were included for meta-analysis. A subgroup analysis was performed based on mismatch repair(MMR) status and regimens. In patients diagnosed with mismatch repair-deficient(dMMR) mCRC who received PD-1/L1 inhibitors as their first-line treatment, the ORR was 0.54 (95% CI, 0.39 to 0.68), the median PFS was 53.2 months, the Grade≥ 3 TRAEs rate was 0.33(95% CI, 0.12 to 0.60) and the median OS was not determined. For patients with proficient mismatch repair (pMMR) mCRC who underwent a combined treatment of PD-1/L1 inhibitors, anti-VEGF monoclonal antibody and chemotherapy as their first-line therapy, the ORR was 0.62 (95% CI, 0.56 to 0.68), the median PFS was 10.1 months, the median OS was 26.7 months, and the Grade≥ 3 TRAEs rate was 0.59(95% CI, 0.39 to 0.77).ConclusionOur results revealed that the utilization of PD-1/L1 inhibitors as first-line therapy for dMMR mCRC yielded highly favorable outcomes, while maintaining an acceptable level of safety. Administering a combination of PD-1/L1 inhibitors, anti-VEGF monoclonal antibody, and chemotherapy as first-line treatment in patients with pMMR mCRC led to an improved ORR. However, there was no significant improvement in the long-term prognosis of the tumor.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024506196, identifier CRD42024506196.
Impact of a passive upper-body exoskeleton on muscular activity and precision in overhead single and dual tasks: an explorative randomized crossover study
Authors: Gräf Julia , Grospretre Sidney , Argubi-Wollesen Andreas , Wollesen Bettina 
Published: July 2024

IntroductionTasks performed at or above head height in industrial workplaces pose a significant challenge due to their association with musculoskeletal disorders. Upper-body exoskeletons have been identified as a potential solution for mitigating musculoskeletal loads and fighting against excessive muscular fatigue. However, the influence of such support on fine motor control, as well as on cognitive-motor interference, has received limited attention thus far. Therefore, this crossover randomized study aimed to investigate the impact of the use of a passive upper-body exoskeleton in the presence of muscular fatigue or not. Additionally, focusing on differences between single (ST) and dual (DT) industrial tasks consisting of overhead speed and accuracy exercises.MethodsIn both scenarios, N = 10 participants (5 male/5 female) engaged in an overhead precision task using a nail gun to precisely target specific areas on three differently sized regions, based on Fitts’ law paradigm (speed-accuracy trade-off task). This was done with and without the passive upper-body exoskeleton, before and immediately after a fatiguing exercise of shoulder and leg muscles. In addition, a second task (dual-task, DT) was carried out in which the occurrence of an auditory signal had to be counted. The main outcomes were muscular activation of the shoulder girdle as well as the time to perform speed-accuracy tasks of different difficulty indexes (calculated by means of Fitts’ law).Results and discussionIn the absence of fatigue, the exoskeleton did not affect the speed-accuracy trade-off management of participants in the single task, but it did in the dual-task conditions. However, after muscle fatigue, the speed-accuracy trade-off was differently affected when comparing its execution with or without the exoskeleton. In general, the dual task resulted in longer times to perform the different tasks, whether it was with or without the exoskeleton. Furthermore, the use of the exoskeleton decreased muscle activity, which is associated with less physical effort, but only significantly for the M. deltoideus and M. trapezius when compared by tasks. Overall, these study findings highlight the potential supportive effects of using an upper-body exoskeleton for industrial overhead tasks.
Association of high fibrinogen to albumin ratio with long-term mortality in patients with spontaneous intracerebral hemorrhage
Authors: Chen Shiping , Zhang Yu , Xiao Yangchun , Cheng Xin , Peng Liyuan , Tian Yixin , Li Tiangui , He Jialing , Hao Pengfei , Chong Weelic , Hai Yang , You Chao , Fang Fang 
Published: July 2024

BackgroundThe association between fibrinogen-to-albumin ratio (FAR) and in-hospital mortality in patients with spontaneous intracerebral hemorrhage (ICH) has been established. However, the association with long-term mortality in spontaneous ICH remains unclear. This study aims to investigate the association between FAR and long-term mortality in these patients.MethodsOur retrospective study involved 3,538 patients who were diagnosed with ICH at West China Hospital, Sichuan University. All serum fibrinogen and serum albumin samples were collected within 24 h of admission and participants were divided into two groups according to the FAR. We conducted a Cox proportional hazard analysis to evaluate the association between FAR and long-term mortality.ResultsOut of a total of 3,538 patients, 364 individuals (10.3%) experienced in-hospital mortality, and 750 patients (21.2%) succumbed within one year. The adjusted hazard ratios (HR) showed significant associations with in-hospital mortality (HR 1.61, 95% CI 1.31–1.99), 1-year mortality (HR 1.45, 95% CI 1.25–1.67), and long-term mortality (HR 1.45, 95% CI 1.28–1.64). Notably, the HR for long-term mortality remained statistically significant at 1.47 (95% CI, 1.15–1.88) even after excluding patients with 1-year mortality.ConclusionA high admission FAR was significantly correlated with an elevated HR for long-term mortality in patients with ICH. The combined assessment of the ICH score and FAR at admission showed higher predictive accuracy for long-term mortality than using the ICH score in isolation.
Effects of perioperative hydrogen inhalation on brain edema and prognosis in patients with glioma: a single-center, randomized controlled study
Authors: Wu Fan , Liang Tao , Liu Yang , Wang Chenhui , Sun Yongxing , Wang Baoguo 
Published: July 2024

IntroductionBrain edema is a life-threatening complication that occurs after glioma surgery. There are no noninvasive and specific treatment methods for brain edema. Hydrogen is an anti-inflammatory and antioxidant gas that has demonstrated therapeutic and preventative effects on several diseases, particularly in the nervous system. This study aimed to determine the therapeutic effects of hydrogen administration on brain edema following glioma surgery and elucidate its mechanism.MethodsA single-center, randomized controlled clinical trial of hydrogen inhalation was conducted (China Clinical Trial Registry [ChiCTR-2300074362]). Participants in hydrogen (H) group that inhaled hydrogen experienced quicker alleviation of postoperative brain edema compared with participants in control (C) group that inhaled oxygen.ResultsThe volume of brain edema before discharge was significantly lower in the H group (p &lt; 0.05). Additionally, the regression rate of brain edema was higher in the H group than in the C group, which was statistically significant (p &lt; 0.05). Furthermore, 3 days after surgery, the H group had longer total sleep duration, improved sleep efficiency, shorter sleep latency, and lower numerical rating scale (NRS) scores (p &lt; 0.05).DiscussionIn conclusion, hydrogen/oxygen inhalation effectively reduced postoperative brain edema in glioma patients. Further research is necessary to understand the underlying mechanisms of hydrogen’s therapeutic effects. Hydrogen is expected to become a new target for future adjuvant therapy for brain edema.
Targeting heme degradation pathway augments prostate cancer cell sensitivity to docetaxel-induced apoptosis and attenuates migration
Authors: Salloom Ramia J. , Ahmad Iman M. , Abdalla Maher Y. 
Published: July 2024

IntroductionChemotherapy, notably docetaxel (Doc), stands as the primary treatment for castration-resistant prostate cancer (CRPC). However, its efficacy is hindered by side effects and chemoresistance. Hypoxia in prostate cancer (PC) correlates with chemoresistance to Doc-induced apoptosis via Heme Oxygenase-1 (HO-1) modulation, a key enzyme in heme metabolism. This study investigated targeting heme degradation pathway via HO-1 inhibition to potentiate the therapeutic efficacy of Doc in PC.MethodsUtilizing diverse PC cell lines, we evaluated HO-1 inhibition alone and with Doc on viability, apoptosis, migration, and epithelial- to- mesenchymal transition (EMT) markers and elucidated the underlying mechanisms.ResultsHO-1 inhibition significantly reduced PC cell viability under hypoxic and normoxic conditions, enhancing Doc-induced apoptosis through interconnected mechanisms, including elevated reactive oxygen species (ROS) levels, glutathione cycle disruption, and modulation of Signal Transducer and Activator of Transcription 1 (STAT1) pathway. The interplay between STAT1 and HO-1 suggests its reliance on HO-1 activation. Additionally, a decrease in cell migration and downregulation of EMT markers (vimentin and snail) were observed, indicating attenuation of mesenchymal phenotype.DiscussionIn conclusion, the combination of HO-1 inhibition with Doc holds promise for improving therapeutic outcomes and advancing clinical management in PC.
RAB42 overexpression correlates with poor prognosis, immune cell infiltration and chemoresistance
Authors: Wang Yang , Xie Youbang , Qian Luomeng , Ding Ran , Pang Rongqing , Chen Ping , Zhang Qing , Zhang Sihe 
Published: July 2024

BackgroundRAB42 (Ras-related protein 42) is a new small GTPase that controls the vesicular trafficking from endosomes to trans-Golgi network in mammalian cells. However, the role of RAB42 in multiple cancers, especially in liver hepatocellular carcinoma (LIHC), has not been well investigated.MethodsA variety of cancer-related databases and online tools, including TCGA, GTEx, TARGET, QUANTISEQ, EPIC, RNAactDrug, CTR-DB, TIMER algorithms and Sangerbox, were applied to explore the correlation of RAB42 expression with prognosis, immune microenvironment, immune regulatory network, RNA modification, pathway activation and drug sensitivity in pan-cancer. The prognostic, immunomodulatory and tumor-promoting effects of RAB42 were verified in various malignancies and determined by a series of in vitro cellular experiments.ResultsRAB42 is significantly overexpressed in most cancers with advanced pathological stages. Its overexpression is correlated with poor survival in pan-cancer. RAB42 overexpression has a high diagnostic accuracy of various cancers (AUC &gt; 0.80). RAB42 overexpression not only correlates with distinct stromal immune infiltration and level of immune checkpoint molecules, but also associates with weak immune cell infiltration, immunomodulatory genes expression, and immunotherapeutic response to immune checkpoint inhibitors (ICIs). Additionally, RAB42 overexpression correlates with enhanced expression of m6A RNA methylation-related genes (MRGs) and its interactors. Moreover, overexpression of RAB42 serves as a drug-resistant marker to certain chemotherapies and acts as a potential biomarker for LIHC. Notably, RAB42 overexpression or activation promotes the cellular proliferation, migration and invasion of LIHC.ConclusionOverexpressed RAB42 serves as a potential prognostic biomarker and therapeutic target in pan-cancer, especially in LIHC.
Cost-effectiveness analysis of pharmaceutical care in adult critically ill patients: based on a prospective cohort study
Authors: Wei Chunyan , Hu Ming , Chen Guanghui , Yan Zhijing , Yin Wanhong , Wu Zhiang 
Published: July 2024

BackgroundThe medication regimen for critically ill patients is complex and dynamic, leading to a high incidence of drug-related problems. This study aimed to assess the effectiveness and economic efficiency of pharmaceutical care for these patients.MethodsIn this prospective cohort study conducted in a tertiary hospital, adult patients were assigned either to a clinical pharmaceutical care group or a control group based on existing clinical grouping rules. Health outcomes and economic indicators were collected, followed by a cost-effectiveness analysis.ResultsThe acceptance rate for clinical pharmacist interventions was 89.31%. The pharmaceutical care group exhibited significant reductions in the rate of medication errors (40.65% vs. 61.69%, P &lt; 0.001) and adverse drug events (44.52% vs. 56.45%, P = 0.020). The usage rates for special-grade antibiotics (85.16% vs. 91.13%, P = 0.009) and proton pump inhibitors (77.42% vs. 88.71%, P = 0.002) were also lower in the pharmaceutical care group. Secondary outcomes did not show significant differences in total hospital stay (21 days vs. 22 days, P = 0.092). However, ICU stay was significantly shorter (9 days vs. 11 days, P = 0.003) in the pharmaceutical care group. Cost-effectiveness analysis demonstrated that each 1% reduction in adverse drug events associated with ICU pharmaceutical care saved $226.75 in ICU hospitalization costs and $203.42 in total ICU drug costs. A 1% reduction in the medication error rate saved $128.57 in ICU hospitalization costs and $115.34 in total ICU drug costs.ConclusionsPharmaceutical care significantly reduces adverse drug events and medication errors, promotes rational use of medications, decreases the length of ICU stay, and lowers treatment costs in critically ill patients, establishing a definitive advantage in terms of cost-effectiveness.