bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations of folate intake with all-cause and cause-specific mortality among individuals with diabetes
Authors: Su Hexin , Bo Yacong , Zhang Xiaoan , Zhang Junxi , Gao Zhan , Yu Zengli 
Published: October 2022

Background and aimsThe evidence regarding folate intake and mortality risk among patients with type 2 diabetes (T2D) remains unclear. This study aimed to investigate the association of folate intake with the risk of mortality among individuals with T2D.MethodsA total of 9,196 participants with T2D from the Third National Health and Nutrition Examination Survey (NHANES III) and NHANES 1999–2014 were included. The data of survival were obtained by the cohort database linked with the national death index up to 31 December 2015. The Cox proportional hazard model was used to evaluate the relationship between dietary folate with all-cause and cause-specific mortality.ResultsAmong patients with T2D, dietary folate intake was negatively correlated with all-cause mortality, cardiovascular mortality, and cancer mortality in men, and for women with all-cause mortality and cardiovascular mortality. The multivariate adjustment hazard ratio (HR) (95% CIs) for men of highest vs. lowest quartile was 0.77 (0.66–0.90), 0.61 (0.45–0.83), and 0.70 (0.49–0.99) for all-cause, cardiovascular, and cancer mortality, respectively. Among women, the multivariate adjustment HR (95% CIs) of highest vs. lowest quartile was 0.77 (0.64–0.92), 0.52 (0.33–0.83), and 0.78 (0.50–1.22) for all-cause, cardiovascular, and cancer mortality, respectively.ConclusionHigher dietary intake of folate was significantly associated with lower all-cause and cardiovascular mortality. This cohort study suggested that increasing the dietary folate intake may reduce mortality risk among U.S. adults with T2D.
The predictive value of patient-reported outcomes on the impact of breast cancer treatment-related quality of life
Authors: Zhou Ke , Bellanger Martine , Le Lann Sophie , Robert Marie , Frenel Jean-Sebastien , Campone Mario 
Published: October 2022

PurposePatient-reported outcomes (PROs) have been widely used to measure breast cancer (BC) treatment outcomes. However, evidence is still limited on using routinely PROs to personalize treatment decision-making, including or not chemotherapy, targeted therapy, and radiotherapy. Using patient baseline PRO scores, we aimed to use PROs before treatment initiation to predict improvement or decline in health-related quality of life (HRQoL) due to treatment that they receive.MethodsIn two French cancer sites, women with non-metastatic BC completed the EORTC QLQ-C30 and QLQ-BR23 and BREAST-Q questionnaires to assess their PROs at baseline and again at 6 months. The outcome measured was post-operative change in PROs with minimal important difference for QLQ-C30 domains. We performed multivariate ordinal logistic regression to estimate the incremental probability of post-operative PRO improvements and deteriorations depending upon treatment options and baseline HRQoL.ResultsOne hundred twenty-seven women completed questionnaires. Chemotherapy had significant negative impacts on Global health status (GHS) and on physical and social functioning. Chemotherapy and radiotherapy increased patient fatigue scores after adjusting for clinical factors (p&lt; 0.01 and p&lt; 0.05, respectively). The incremental probability of GHS deteriorations for chemotherapy was +0.3, +0.5, and +0.34 for patients with baseline GHS scores of 40, 70, and 100, respectively. This showed that different pre-treatment PROs might predict differential effects of chemotherapy on women change in HRQoL.ConclusionPatients with different baseline PRO scores may experience dissimilar impacts from BC treatments on post-operative PROs in terms of improvements and deteriorations. Oncologists might decide to adapt the treatment option based on a given level of the negative impact. Future studies should concentrate on incorporating this information into routine clinical decision-making strategies to optimize the treatment benefit for patients.
Impact of skeletal muscle loss during conversion therapy on clinical outcomes in lavage cytology positive patients with gastric cancer
Authors: Ding Ping’an , Yang Peigang , Yang Li , Sun Chenyu , Chen Shuya , Li Min , Lowe Scott , Guo Honghai , Tian Yuan , Liu Yang , Zhao Qun 
Published: October 2022

BackgroundThe relationship between sarcopenia and clinical outcomes during conversion therapy in patients with lavage cytology positive gastric cancer (GC-CY1) remains unclear. This study aimed to investigate the impact of sarcopenia and skeletal muscle loss on the efficacy of conversion therapy, tumour response and survival in GC-CY1 patients.MethodsRetrospective analysis of data from a prospective trial of conversion therapy conducted between April 2018 and August 2019 in patients with GC-CY1 (NCT03718624). Skeletal muscle index (SMI) was measured at the level of the third lumbar (L3) vertebra and the sarcopenia was defined using published cut-off points in all patients. We defined ΔSMI (%)/50 days above 9.53% for men and ΔSMI (%)/50 days above 8.81% for women as significant muscle loss (SML) and analysed the changes in skeletal muscle during conversion therapy in relation to treatment efficacy, survival and tumour response.ResultsOf the 36 patients, 7 patients (19.44%) developed sarcopenia before conversion therapy, 6 (16.67%) developed new sarcopenia after conversion therapy, and 8 (22.22%) developed SML during treatment. Multivariate analysis showed that sarcopenia before treatment [Odds Ratio (OR) =8.923, 95%CI: 1.341-25.321, p=0.002] and SML during treatment (OR=7.803, 95%CI: 1.106-16.189, p=0.001) had a negative impact on the success rate of conversion therapy. Cox multifactorial analysis found that pre-treatment sarcopenia [overall survival (OS): Hazard Ratio (HR) =6.341, 95%CI: 1.269-18.943, p=0.001; progression-free survival (PFS): HR=8.212, 95%CI: 1.569-36.582, p=0.001], newly developed sarcopenia after conversion therapy (OS: HR=3.189, 95%CI: 1.023-9.811, p=0.012; PFS: HR=3.084, 95%CI: 1.042-14.236, p=0.013) and the presence of SML during treatment (OS: HR=10.234, 95%CI: 2.532-54.231, p=0.002; PFS: HR=9.562, 95%CI: 2.341-38.092, p=0.002) were independent risk factor for OS and PFS in GC-CY1 patients.ConclusionPre-treatment sarcopenia and the presence of SML during treatment are strongly correlated with the immediate and long-term outcomes of GC-CY1 patients and can be used as imaging markers to predict the treatment efficacy and prognosis of patients in clinical practice.
Improving radiomic model reliability using robust features from perturbations for head-and-neck carcinoma
Authors: Teng Xinzhi , Zhang Jiang , Ma Zongrui , Zhang Yuanpeng , Lam Saikit , Li Wen , Xiao Haonan , Li Tian , Li Bing , Zhou Ta , Ren Ge , Lee Francis Kar-ho , Au Kwok-hung , Lee Victor Ho-fun , Chang Amy Tien Yee , Cai Jing 
Published: October 2022

BackgroundUsing high robust radiomic features in modeling is recommended, yet its impact on radiomic model is unclear. This study evaluated the radiomic model’s robustness and generalizability after screening out low-robust features before radiomic modeling. The results were validated with four datasets and two clinically relevant tasks.Materials and methodsA total of 1,419 head-and-neck cancer patients’ computed tomography images, gross tumor volume segmentation, and clinically relevant outcomes (distant metastasis and local-regional recurrence) were collected from four publicly available datasets. The perturbation method was implemented to simulate images, and the radiomic feature robustness was quantified using intra-class correlation of coefficient (ICC). Three radiomic models were built using all features (ICC &gt; 0), good-robust features (ICC &gt; 0.75), and excellent-robust features (ICC &gt; 0.95), respectively. A filter-based feature selection and Ridge classification method were used to construct the radiomic models. Model performance was assessed with both robustness and generalizability. The robustness of the model was evaluated by the ICC, and the generalizability of the model was quantified by the train-test difference of Area Under the Receiver Operating Characteristic Curve (AUC).ResultsThe average model robustness ICC improved significantly from 0.65 to 0.78 (P&lt; 0.0001) using good-robust features and to 0.91 (P&lt; 0.0001) using excellent-robust features. Model generalizability also showed a substantial increase, as a closer gap between training and testing AUC was observed where the mean train-test AUC difference was reduced from 0.21 to 0.18 (P&lt; 0.001) in good-robust features and to 0.12 (P&lt; 0.0001) in excellent-robust features. Furthermore, good-robust features yielded the best average AUC in the unseen datasets of 0.58 (P&lt; 0.001) over four datasets and clinical outcomes.ConclusionsIncluding robust only features in radiomic modeling significantly improves model robustness and generalizability in unseen datasets. Yet, the robustness of radiomic model has to be verified despite building with robust radiomic features, and tightly restricted feature robustness may prevent the optimal model performance in the unseen dataset as it may lower the discrimination power of the model.
Serum exosomal and serum glypican-1 are associated with early recurrence of pancreatic ductal adenocarcinoma
Authors: Zhao Juan , Guo Madi , Song Yushuai , Liu Shan , Liao Ran , Zhang Yu , Zhang Yumin , Yang Qi , Gu Yuanlong , Huang Xiaoyi 
Published: October 2022

BackgroundThe diagnostic performance and prognostic value of serum exosomal glypican 1 (GPC-1) in pancreatic ductal adenocarcinoma (PDAC) remain controversial. In this study, we detected serum exosomal GPC-1 using enzyme-linked immunosorbent assay (ELISA) and determined whether it serves as a predictor of diagnosis and recurrence for early-stage PDAC.MethodsSerum samples were obtained from patients with 50 PDAC, 6 benign pancreatic tumor (BPT), or 9 chronic pancreatitis (CP) and 50 healthy controls (HCs). Serum exosomes were isolated using an exosome isolation kit. Exosomal and serum GPC-1 levels were measured using ELISA. The freeze–thaw process was carried out to analyze the stability of GPC-1. Receiver operating characteristic (ROC) analysis was employed to assess the diagnostic value of GPC-1. Kaplan–Meier and multivariate Cox analyses were used to evaluate the prognostic value of GPC-1.ResultsThe average concentrations of serum exosomal and serum GPC-1 were 1.5 and 0.8 ng/ml, respectively. GPC-1 expression levels were stable under repeated freezing and thawing (d1-5 freeze–thaw cycles vs. d0 P &gt; 0.05). Serum exosomal and serum GPC-1 were significantly elevated in patients with PDAC compared with HCs (P &lt; 0.0001) but were slightly higher compared with that in patients with CP and BPT (P &gt; 0.05). The expression levels of exosomal and serum GPC-1 were elevated 5 days after surgery in patients with PDAC, CP, and BPT (P &lt; 0.05). Patients with high levels of exosomal and serum GPC-1 had a shorter relapse-free survival (RFS) (P = 0.006, and P = 0.010). Multivariate analyses showed that serum exosomal and serum GPC-1 were independent prognostic indicators for early RFS (P = 0.008, and P = 0.041).ConclusionELISA is an effective and sensitive method to detect exosomal and serum GPC-1. The detection of GPC-1 was stable under repeated freezing and thawing cycles and could distinguish early-stage PDAC from HCs but not CP and BPT. Exosomal and serum GPC-1 may be good independent predictors of early recurrence in early-stage PDAC.
Prevalence and predictors of medication-related emergency department visit in older adults: A multicenter study linking national claim database and hospital medical records
Authors: Park Soyoung , Kim A Jeong , Ah Young-Mi , Lee Mee Yeon , Lee Yu Jeong , Chae Jungmi , Rho Ju Hyun , Kim Dong-Sook , Lee Ju-Yeun 
Published: October 2022

Objectives: Older adults are more likely to experience drug-related problems (DRP), which could lead to medication-related emergency department visits (MRED). To properly evaluate MRED, the entire history of drug use should be evaluated in a structured manner. However, limited studies have identified MRED with complete prescription records. We aimed to evaluate the prevalence and risk factors of MRED among community-dwelling older patients by linking national claims data and electronic medical records using a standardized medication related admission identification method.Methods: We included older patients who visited the emergency departments of four participating hospitals in 2019. Among the 54,034 emergency department (ED) visitors, we randomly selected 6,000 patients and structurally reviewed their medical records using a standardized MRED identification method after linking national claims data and electronic medical records. We defined and categorized MRED as ED visits associated with adverse drug events and those caused by the underuse of medication, including treatment omission and noncompliance and assessed as having probable or higher causality. We assessed preventability using Schumock and Thornton criteria.Results: MRED was observed in 14.3% of ED visits, of which 76% were preventable. In addition, 32.5% of MRED cases were related to underuse or noncompliance, and the rest were related to adverse drug events. Use of antipsychotics, benzodiazepines, anticoagulants, traditional nonsteroidal anti-inflammatory drugs without the use of proton pump inhibitors, P2Y12 inhibitors, insulin, diuretics, and multiple strong anticholinergic drugs were identified as predictors of MRED.Conclusion: One in seven cases of ED visits by older adults were medication related and over three-quarters of them were preventable. These findings suggest that DRPs need to be systemically screened and intervened in older adults who visit ED.
Novel ultrashort-acting benzodiazepine remimazolam lowers shivering threshold in rabbits
Authors: Muroya Kenji , Ueda Kenta , Wada Keiichi , Kotoda Masakazu , Matsukawa Takashi 
Published: October 2022

Shivering after surgery or during therapeutic hypothermia can lead to serious complications, such as myocardial infarction and respiratory failure. Although several anesthetics and opioids are shown to have anti-shivering effects, their sedative and respiratory side effects dampen the usefulness of these drugs for the prevention of shivering. In the present study, we explored the potential of a novel ultrashort-acting benzodiazepine, remimazolam, in the prevention of shivering using a rabbit model of hypothermia. Adult male Japanese white rabbits were anesthetized with isoflurane. The rabbits received saline (control), remimazolam (either 0.1 or 1 mg/kg/h), or remimazolam + flumazenil, a selective γ-aminobutyric acid (GABA) type A receptor antagonist (n = 6 each). Thirty minutes after discontinuation of the drugs, cooling was initiated by perfusing 10°C water via a plastic tube positioned in the colon until the animal shivered. Core body temperature and hemodynamic and physiological parameters were recorded. Remimazolam at 1 mg/kg/h significantly lowered the core temperature change during shivering (−2.50 ± 0.20°C vs. control: −1.00 ± 0.12°C, p = 0.0009). The effect of 1 mg/kg/h remimazolam on the core temperature change was abolished by flumazenil administration (−0.94 ± 0.16°C vs. control: −1.00 ± 0.12°C, p = 0.996). Most of the hemodynamic and physiological parameters did not differ significantly among groups during cooling. Remimazolam at a clinically relevant dose successfully suppressed shivering in rabbits via the GABA pathway even after its anesthetic effects likely disappeared. Remimazolam may have the potential to prevent shivering in patients undergoing surgery or therapeutic hypothermia.
Sodium–Glucose cotransporter 2 inhibitor empagliflozin decreases ventricular arrhythmia susceptibility by alleviating electrophysiological remodeling post-myocardial-infarction in mice
Authors: Xue Genlong , Yang Xiaolei , Zhan Ge , Wang Xin , Gao Jinghan , Zhao Yong , Wang Xinying , Li Jiatian , Pan Zhenwei , Xia Yunlong 
Published: October 2022

Background: Recent clinical trials indicate that sodium–glucose cotransporter 2 (SGLT2) inhibitors improve cardiovascular outcomes in myocardial infarction (MI) patients, but the underlying mechanisms remain unknown. As arrhythmia often occurs during myocardial infarction, it is the main cause of death.Objective: The purpose of this study was to investigate the influence of empagliflozin (EMPA), an SGLT2 inhibitor, on cardiac electrophysiological remodeling and arrhythmia susceptibility of myocardial infarction mice.Methods: ECG was obtained from mice 1 week after MI to determine the QT interval. In an electrophysiological study and optical mapping was performed to evaluate the function of EMPA and underlying mechanisms of post-myocardial-infarction in mice.Results: EMPA treatment significantly reduced the QT interval of MI mice (MI + EMPA 50.24 ms vs. MI 64.68 ms). The membrane potential and intracellular Ca [Cai] were mapped from 13 MI hearts and five normal hearts using an optical mapping technique. A dynamic pacing protocol was used to determine action potential duration and [Cai] at baseline and after EMPA (10 umol/L) infusion. EMPA perfusion did not change the APD80 and CaT80 in normal ventricles while shortening them in an infarct zone, bordering zone, and remote zone of MI hearts at 200 ms, 150 ms, 120 ms, and 100 ms pacing cycle length. The conduction velocity of infarcted ventricles was 0.278 m/s and 0.533 m/s in normal ventricles at baseline (p &lt; 0.05). After EMPA administration, the conduction velocity of infarcted ventricles increased to 0.363 m/s, whereas no significant changes were observed in normal ventricles. The action potential rise time, CaT rise time, and CaT tau time were improved after EMPA perfusion in infarcted ventricles, whereas no significant changes were observed in normal ventricles. EMPA decreases early afterdepolarizations premature ventricular beats, and ventricular fibrillation (VF) in infarcted ventricles. The number of phase singularities (baseline versus EMPA, 6.26 versus 3.25), dominant frequency (20.52 versus 10.675 Hz), and ventricular fibrillation duration (1.072 versus 0.361 s) during ventricular fibrillation in infarcted ventricles were all significantly decreased by EMPA.Conclusion: Treatment with EMPA improved post-MI electrophysiological remodeling and decreased substrate for VF of MI mice. The inhibitors of SGLT2 may be a new class of agents for the prevention of ventricle arrhythmia after chronic MI.
Inhibition of inflammatory liver injury by the HMGB1-A box through HMGB1/TLR-4/NF-κB signaling in an acute liver failure mouse model
Authors: Luo Lidan , Wang Shuai , Chen Bohao , Zhong Mei , Du Ruili , Wei ChunShan , Huang Furong , Kou Xinhui , Xing Yufeng , Tong Guangdong 
Published: October 2022

We aimed to investigate the preventive effect of high mobility group box 1 (HMGB1)-A box and the mechanism by which it alleviates inflammatory injury in acute liver failure (ALF) by inhibiting the extracellular release of HMGB1. BALB/c mice were intraperitoneally (i.p.) administered LPS/D-GalN to establish an ALF mouse model. HMGB1-A box was administered (i.p.) 1 h before establishing the ALF mouse model. The levels of extracellularly released HMGB1, TLR-4/NF-κB signaling molecules, the proinflammatory cytokines TNF-α, IL-1β, and IL-6 and COX-2 were measured in the liver tissue and/or serum by Immunohistochemistry, Western blotting and Enzyme-linked immunosorbent assay (ELISA). The levels of extracellularly released HMGB1, TLR-4/NF-κB signaling molecules and proinflammatory cytokines were measured in Huh7 cells as well as LPS- and/or HMGB1-A box treatment by confocal microscopy, Western blotting and ELISA. In the ALF mouse model, the levels of HMGB1 were significantly increased both in the liver and serum, TLR-4/NF-κB signaling molecules and proinflammatory cytokines also was upregulated. Notably, HMGB1-A box could reverse these changes. HMGB1-A box could also cause these changes in LPS-induced Huh7 cells. HMGB1-A box played a protective role by inhibiting inflammatory liver injury via the regulation of HMGB1/TLR-4/NF-κB signaling in the LPS/D-GaIN-induced ALF mouse model, which may be related to inhibiting the extracellular release of HMGB1.
An exploratory, open-label, randomized, multicenter trial of hachimijiogan for mild Alzheimer’s disease
Authors: Kainuma Mosaburo , Ouma Shinji , Kawakatsu Shinobu , Iritani Osamu , Yamashita Ken-Ichiro , Ohara Tomoyuki , Hirano Shigeki , Suda Shiro , Hamano Tadanori , Hieda Sotaro , Yasui Masaaki , Yoshiiwa Aoi , Shiota Seiji , Hironishi Masaya , Wada-Isoe Kenji , Sasabayashi Daiki , Yamasaki Sho , Murata Masayuki , Funakoshi Kouta , Hayashi Kouji , Shirafuji Norimichi , Sasaki Hirohito , Kajimoto Yoshinori , Mori Yukiko , Suzuki Michio , Ito Hidefumi , Ono Kenjiro , Tsuboi Yoshio 
Published: October 2022

Background: Alzheimer’s disease (AD) is a progressive neurodegeneration and is the most prevalent form of dementia. Intervention at an early stage is imperative. Although three acetylcholinesterase inhibitors (AChEIs) are currently approved for the treatment of mild AD, they are not sufficiently effective. Novel treatments for mild AD are of utmost importance.Objective: To assess the effectiveness of hachimijiogan (HJG), a traditional Japanese herbal medicine (Kampo), in the treatment of mild AD.Methods: This exploratory, open-label, randomized, multicenter trial enrolled patients with mild AD whose score on the Mini Mental State Examination (MMSE) was over 21points. All participants had been taking the same dosage of AChEI for more than 3 months. The participants were randomly assigned to an HJG group taking HJG extract 7.5 g/day in addition to AChEI or to a control group treated only with AChEI. The primary outcome was the change from baseline to 6 months post treatment initiation on the Alzheimer’s Disease Assessment Scale-cognitive component- Japanese version(ADAS-Jcog). The secondary outcomes were change from baseline of the Instrumental Activity of Daily Life (IADL), Apathy scale, and Neuropsychiatric Inventory (NPI) -Q score.Results: Among the 77 enrollees, the data of 69(34 HJG and 35 control)were available for analysis. The difference in the change of ADAS-Jcog from baseline to 6 months of the HJG and control groups was 1.29 (90% Confidence interval (CI), −0.74 to 3.32 p = 0.293). In the subgroup analysis, the differences in the change from baseline to 3 and 6 months for women were 3.70 (90% CI ,0.50 to 6.91, p = 0.059) and 2.90 (90% CI,0.09 to 5.71, p = 0.090), respectively. For patients over 65 years, the difference at 3 months was 2.35 (90%CI, 0.01 to 4.68 p = 0.099). No significant differences were found between the HJG and control groups in IADL score, Apathy scale, or NPI-Q score.Conclusion: Although not conclusive, our data indicate that HJG has an adjuvant effect for acetylcholinesterase inhibitors and that it delays the deterioration of the cognitive dysfunction of mild Altzheimer’s disease patients.Clinical Trial Registration:http://clinicaltrials.gov Japan Registry of clinical trials, identifier jRCTs 071190018