bluuebunny/crossref_metadata_2025_split huggingface dataset:
Triglyceride glucose index and its combination with the Get with the Guidelines-Heart Failure score in predicting the prognosis in patients with heart failure
Authors: Han Su , Wang Chuanhe , Tong Fei , Li Ying , Li Zhichao , Sun Zhaoqing , Sun Zhijun 
Published: September 2022

BackgroundHeart failure (HF) is associated with generalized insulin resistance (IR). Recent studies demonstrated that triglyceride glucose (TyG) is an effective alternative index of IR. However, the relationship between the TyG index and in-hospital mortality in patients with HF is unclear. In the present study, we aimed to clarify the association between the TyG index and in-hospital mortality in patients with HF.MethodsA retrospective study consisting of 4,411 patients diagnosed with HF from 2015 to 2018 was conducted. All-cause mortality during hospitalization was the primary endpoint. The association between the TyG index and in-hospital mortality was assessed using the logistic regression analysis.ResultsThe risk of in-hospital mortality was significantly associated with increased TyG index (OR: 1.886, 95% CI: 1.421–2.501, p &lt; 0.001) under logistic regression with multivariable adjustment. When divided into three groups based on the TyG index, Tertile 3 demonstrated significantly higher in-hospital mortality than the other two Tertiles (OR: 2.076, 95% CI: 1.284–3.354, p = 0.001). Moreover, the TyG index improved the prediction efficiency of the Get with the Guidelines-Heart Failure (GWTG-HF) score (absolute integrated discrimination improvement = 0.006, p &lt; 0.001; category-free net reclassification improvement = 0.075, p = 0.005). In subgroup analysis, the TyG index exhibited similar predictive performance of in-hospital mortality when groups were stratified based on type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD).ConclusionTyG is a potential index for predicting in-hospital mortality in patients with HF, independent of T2DM or CAD status. The TyG index may be combined with the GWTG-HF score to further improve its predictive efficacy.
Prediction value of 18F-FDG PET/CT intratumor metabolic heterogeneity parameters for recurrence after radical surgery of stage II/III colorectal cancer
Authors: Liu Xin , Zhang Yi-Fan , Shi Qin , Yang Yi , Yao Ben-Hu , Wang Shi-Cun , Geng Guang-Yong 
Published: September 2022

PurposeWe explored the predictive effect of intratumor metabolic heterogeneity indices extracted from 18F-FDG PET/CT on recurrence in stage II/III colorectal cancer after radical surgery.MethodsA total of 140 stage II/III colorectal cancer patients who received preoperative 18F-FDG PET/CT and radical resection were enrolled. 18F-FDG traditional parameters including the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) under different thresholds; heterogeneity indices including the coefficient of variation with SUV 2.5 as a threshold (CV2.5), CV40%, heterogeneity index-1 (HI-1) calculated by the fixed-threshold method, and HI-2 calculated by the percentage threshold method; and clinicopathological information were collected. We concluded that relationships exist between these data and patients’ disease-free survival (DFS).ResultsRegional lymph node status (P &lt; 0.001), nerve invasion (P = 0.036), tumor thrombus (P = 0.005), and HI-1 (P = 0.010) exhibited significant differences between the relapse and non-relapse groups, while SUVmax, MTV2.5, MTV40%, TLG2.5, TLG40%, CV2.5, CV40%, HI-2, and other clinicopathological factors had no differences between the relapse and non-relapse groups. Multivariate analysis demonstrated that HI-1 (HR = 1.02, 1.00–1.04, P = 0.038), regional lymph node metastasis (HR = 2.95, 1.37–6.38, P = 0.006), and tumor thrombus status (HR = 2.37, 1.13–4.99, P = 0.022) were independent factors significantly related to DFS.ConclusionHI-1, tumor thrombus status, and regional lymph node status could predict the recurrence of stage II/III colorectal cancer after radical resection and had an advantage over other 18F-FDG PET/CT conventional parameters and heterogeneity indices.
Could fertility-sparing surgery be considered for stage I ovarian sex cord-stromal tumors? A comparison of the Fine-Gray model with Cox model
Authors: Sun Dan , Zhi Zhi F. , Fan Jiang T. 
Published: September 2022

ObjectiveTo evaluate the oncologic outcomes in patients with International Federation of Gynecology and Obstetrics (FIGO) stage I ovarian sex cord-stromal tumors (SCSTs) who underwent fertility-sparing surgery (FSS) and the independent risk factors affecting overall survival (OS) and cancer-specific survival (CSS).MethodsData were acquired from the Surveillance, Epidemiology, and End Results (SEER) database between 1973 and 2018. A total of 240 patients diagnosed with stage I ovarian SCSTs were divided into the definitive surgery group (N=116) and FSS group (N=124). The Kaplan-Meier analysis and Cox model were used to evaluate the overall survival (OS) and cancer-specific survival (CSS) of the two groups and assess the independent risk factors respectively. The Fine-Gray model evaluated cancer-specific mortality (CSM) and the independent risk factors that affected CSM.ResultsKaplan-Meier survival analysis showed no statistically significant differences in OS and CSS between the two groups (P&gt;0.05). Univariate analysis of the Fine-Gray model also showed that there was no difference in the CSS between the two groups (P&gt;0.05). However, from the 15th year postoperatively, the CSS of the FSS group decreased by 13.21% compared with that of the control group and by 17.49% in the 20th and 25th years postoperatively. The Cox proportional hazards model found that surgical methods (“defined surgery” vs “FSS”; HR=0.03259, P=0.0196) and FIGO stage (“stage IA” vs “stage IC”; HR=0.03073, P=0.0300) were independent risk factors for OS. The multivariate analysis of Fine-Gray model showed that the cancer-specific mortality of patients receiving definitive surgery was 40.1% lower than that of patients receiving FSS (“definitive surgery” vs “FSS”; HR=0.599, P=0.005), indicating that FSS might lead to higher tumor-specific mortality and lower CSS. However, age, race, laterality, history, FIGO stage, and tumor size had no significant influence on the tumor-specific mortality (P&gt;0.05).ConclusionsFSS is considered for patients with stage I SCSTs with reproductive needs, but the follow-up period should not be less than 15 years. For patients with stage IC disease, FSS should be selected carefully, and close follow-up is necessary. Perhaps, definitive surgery after birth is a means to improve long-term survival rates.
Calcium dobesilate efficiency in the treatment of diabetic kidney disease through suppressing MAPK and chemokine signaling pathways based on clinical evaluation and network pharmacology
Authors: Du Bingyu , Yin Yanyan , Wang Yuqing , Fu Hui , Sun Helin , Yue Zhaodi , Yu Shaohong , Zhang Zhongwen 
Published: September 2022

Aims: To evaluate the effectiveness and potential mechanism of calcium dobesilate (CaD) in diabetic kidney disease (DKD) patients.Methods: We searched for available randomized controlled studies on DKD patients’ treatment with CaD through open databases. Continuous variables were expressed as standardized mean difference (SMD) with a 95% confidence interval (CI). The putative targets and possible pathways of CaD on DKD were analyzed by network pharmacology. Molecular docking was employed to verify the match between CaD and the target genes.Results: In the meta-analysis, 42 trials were included, involving 3,671 DKD patients, of which 1,839 received CaD treatment in addition to conventional treatment, while 1,832 received conventional treatment. Compared with routine therapy, the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) significantly decreased in the CaD treatment (early stage of DKD, Scr: p &lt; 0.00001; BUN: p &lt; 0.0001; clinical stage of DKD, Scr: p &lt; 0.00001; BUN: p &lt; 0.00001; kidney failure stage, Scr: p = 0.001; BUN: p = 0.004). The levels of serum cystatin C (Cys-C), urine levels of molecules reflecting kidney function (urinary albumin excretion rate (UAER) and micro glycoprotein), and inflammatory factors [hypersensitive c-reactive protein (hs-CRP)] were reduced compared with control groups, while glomerular filtration rate (GFR) was increased in patients treated with CaD for 12 weeks. CaD also showed a better effect on improving endothelial function. Network pharmacology results showed that the interaction pathway between CaD and DKD was mainly enriched in MAPK and chemokine signaling pathways. AKT1, CASP3, IGF1, MAPK8, and CCL5 might be the key targets for CaD in treating DKD.Conclusion: Combination with CaD is effective and safe in patients with DKD. Inhibition of MAPK and chemokine signaling pathways might be vital in treating CaD in DKD patients.
Nanogels as target drug delivery systems in cancer therapy: A review of the last decade
Authors: Attama Anthony A. , Nnamani Petra O. , Onokala Ozioma B. , Ugwu Agatha A. , Onugwu Adaeze L. 
Published: September 2022

Cancer is an important cause of morbidity and mortality worldwide, irrespective of the level of human development. Globally, it was estimated that there were 19.3 million new cases of cancer and almost 10 million deaths from cancer in 2020. The importance of prevention, early detection as well as effective cancer therapies cannot be over-emphasized. One of the important strategies in cancer therapy is targeted drug delivery to the specific tumor sites. Nanogels are among the several drug delivery systems (DDS) being explored as potential candidates for targeted drug delivery in cancer therapy. Nanogels, which are new generation, versatile DDS with the possession of dual characteristics of hydrogels and nanoparticles have shown great potential as targeted DDS in cancer therapy. Nanogels are hydrogels with a three-dimensional (3D) tunable porous structure and a particle size in the nanometre range, from 20 to 200 nm. They have been visualized as ideal DDS with enormous drug loading capacity, and high stability. Nanogels can be modified to achieve active targeting and enhance drug accumulation in disease sites. They can be designed to be stimulus-responsive, and react to internal or external stimuli such as pH, temperature, light, redox, thus resulting in the controlled release of loaded drug. This prevents drug accumulation in non-target tissues and minimizes the side effects of the drug. Drugs with severe adverse effects, short circulation half-life, and easy degradability by enzymes, such as anti-cancer drugs, and proteins, are suitable for delivery by chemically cross-linked or physically assembled nanogel systems. This systematic review summarizes the evolution of nanogels for targeted drug delivery for cancer therapy over the last decade. On-going clinical trials and recent applications of nanogels as targeted DDS for cancer therapy will be discussed in detail. The review will be concluded with discussions on safety and regulatory considerations as well as future research prospects of nanogel-targeted drug delivery for cancer therapy.
Using a competitive counterflow assay to identify novel cationic substrates of OATP1B1 and OATP1B3
Authors: Schnegelberger Regina D. , Steiert Brianna , Sandoval Philip J. , Hagenbuch Bruno 
Published: September 2022

OATP1B1 and OATP1B3 are two drug transporters that mediate the uptake of multiple endo- and xenobiotics, including many drugs, into human hepatocytes. Numerous inhibitors have been identified, and for some of them, it is not clear whether they are also substrates. Historically radiolabeled substrates or LC-MS/MS methods were needed to test for transported substrates, both of which can be limiting in time and money. However, the competitive counterflow (CCF) assay originally described for OCT2 and, more recently, for OCT1, OATP2B1, and OATP1A2 does not require radiolabeled substrates or LC-MS/MS methods and, as a result, is a more cost-effective approach to identifying substrates of multidrug transporters. We used a CCF assay based on the stimulated efflux of the common model substrate estradiol-17β-glucuronide (E17βG) and tested 30 compounds for OATP1B1- and OATP1B3-mediated transport. Chinese Hamster Ovary (CHO) cells stably expressing OATP1B1 or OATP1B3 were preloaded with 10 nM [3H]-estradiol-17β-glucuronide. After the addition of known substrates like unlabeled estradiol-17β-glucuronide, estrone-3-sulfate, bromosulfophthalein, protoporphyrin X, rifampicin, and taurocholate to the outside of the preloaded CHO cells, we observed efflux of [3H]-estradiol-17β-glucuronide due to exchange with the added compounds. Of the tested 30 compounds, some organic cation transporter substrates like diphenhydramine, metformin, and salbutamol did not induce [3H]-estradiol-17β-glucuronide efflux, indicating that the two OATPs do not transport them. However, 22 (for OATP1B1) and 16 (for OATP1B3) of the tested compounds resulted in [3H]-estradiol-17β-glucuronide efflux, suggesting that they are OATP substrates. Among these compounds, we further tested clarithromycin, indomethacin, reserpine, and verapamil and confirmed that they are substrates of the two OATPs. These results demonstrate that the substrate spectrum of the well-characterized organic anion transporting polypeptides includes several organic cations. Furthermore, as for other drug uptake transporters, the CCF assay is an easy-to-use screening tool to identify novel OATP substrates.
Associations of muscle-strengthening exercise with overweight, obesity, and depressive symptoms in adolescents: Findings from 2019 Youth Risk Behavior Surveillance system
Authors: Shi Jizu , Gao Mingjun , Xu Xiao , Zhang Xuyang , Yan Jin 
Published: September 2022

BackgroundPrevious studies have focused on the opposite relation between muscle strength, obesity, and depression in adults. Moreover, the evidence has indicated that obesity and depression in adults might be significantly decreased with Muscle Strength Exercise (MSE) albeit it might be insufficient. Therefore, the current study aimed to investigate the association between MSE, adiposity, and depression among United States adolescents.Materials and methodsThis cross-sectional study used the Youth Risk Behavioral Survey (YRBS) data. In YRBS, a cluster sample was used, and the investigation was divided into three stages. The study surveyed 13,677 high school students and conducted self-reported questionnaires on sex, grade, race/ethnicity, MSE days, overweight, obesity, and depressive symptoms. The study got the nationally representative population of American students in Grade 9 to 12 (around 12–18 years).ResultsA total of 13,677 participants (female = 6,885, male = 6641) were included in the final analysis. The participants meeting the guidelines’ requirements seemed more likely to be obese than those not meeting (OR = 1.28, 95% CI = 1.06–1.55). There was no statistical significance in the relations between the MSE guidelines and overweight and depression (OR = 0.86, 95% CI = 0.73–1.01: OR = 0.94, 95% CI = 0.83–1.06). For all the participants, the prevalence of those conforming to MSE was 30.1%. One-fifth of the participants reported no MSE per week, 7.8% reported 3 days of MSE per week, and 7.7% reported 7 days.ConclusionThe main finding of this study indicated a positive relationship between the normative MSE required in guidelines and low-level obesity. Beyond that, the evidence was insufficient to confirm the positive links between MSE and depression among American adolescents. Our study could offer evidence for future MSE interventions in adolescents.
Association between social capital and self-rated health among community-dwelling older adults
Authors: Bai Zhongliang , Yang Jing , Wang Zijing , Cao Wenwen , Cao Chenglin , Hu Zhi , Chen Ren 
Published: September 2022

BackgroundIt is less known about whether the association of social capital with self-rated health (SRH) varies by the presence of health conditions and how social capital, together with other variables, is linked to self-rated health in later life.ObjectivesThis article aimed to explore the association of social capital with self-rated health and to examine whether the association varies among older people with and without health conditions, with a special focus on how social capital and relevant factors have an effect on self-rated health among community-dwelling older adults.MethodsCross-sectional data were obtained from a survey that commenced from July to September 2017 in Anhui Province. Data on socio-demographic information, social capital (six dimensions), and self-rated health were analyzed. Binary logistic regression and classification and regression tree (CART) models were used to estimate the association.ResultsBased on the findings, we found that social capital regarding less social support (adjusted odds ratio (AOR) = 1.57, 95% CI: 1.21–2.04), and less reciprocity (AOR = 1.73, 95% CI: 1.29–2.31) were associated with self-rated health among general older adults. Social capital as measured by less social participation (AOR = 1.55, 95% CI: 1.06–2.27), less cohesion (AOR = 0.63, 95% CI: 0.42–0.94), and less reciprocity (AOR =1.77, 95% CI: 1.17–2.68) were linked to self-rated health among older people with health conditions. While social capital regarding less social support (AOR = 2.15, 95% CI: 1.39–3.33) was related to self-rated health among older people without health conditions. We observed the interacting effect of social capital in the CART model, an implication that much focus should be geared toward vulnerable subgroups, especially depressed and lonely older people, as they have low reciprocity and little cohesion.ConclusionThis work demonstrates that social capital may be relevant in devising programs and measures to improve self-rated health among community-dwelling older adults with comorbidity.
Factors associated with renal function state transitions: A population-based community survey in Taiwan
Authors: Tsai Ming-Hsien , Lin Ming-Yen , Hsu Chen-Yang , Yen Amy Ming-Fang , Chen Tony Hsiu-Hsi , Chiu Sherry Yueh-Hsia , Hwang Shang-Jyh 
Published: September 2022

BackgroundUnderstanding renal function state transition risk and associated factors in community residences is vital for appropriate preventive and care actions. We aim to investigate factors affecting renal function state transitions through 10-year longitudinal community screening surveys.MethodsThe prospective cohort study included participants who attended the screening program ≥2 times from 2001 to 2009 and were divided into two cohorts: those with baseline estimated glomerular filtration rate (eGFR) ≥60 (n = 46,278) and those with eGFR 59–30 mL/min/1.73 m2 (n = 4,656). We applied the illness-death model to identify associated factors with eGFR &lt;60 and death for the cohort with baseline eGFR ≥60 and eGFR &lt;30 and death for that with baseline eGFR ≥59–30.ResultsAmong the followed-up participants, 3,018 (6.5%) in the cohort of baseline eGFR ≥60 mL/min/1.73 m2 and 322 (6.9%) in the cohort of eGFR 59–30 mL/min/1.73 m2 experienced renal function state transition during a median over 7-year follow-up. Besides eGFR and grade of proteinuria, diabetes mellitus (adding nearly 50% hazard rate) is the main factor associated with both state transitions. Other early-phase eGFR state transition risk factors were metabolic syndrome score, triglyceride, uric acid, fasting blood sugar, and high-density lipoprotein cholesterol. Males, poor hemoglobin, high triglyceride, and high low-density lipoprotein cholesterol were all linked with the late-phase eGFR state transition hazard rate.ConclusionThe study developed the state transition functions for community participants with varying renal function levels. Further actions to develop precision screening plans and services that incorporate personal risk factors and state transition risks are necessary.
Effect of Resveratrol Supplementation on Intestinal Oxidative Stress, Immunity and Gut Microbiota in Weaned Piglets Challenged with Deoxynivalenol
Authors: Qiu Yueqin , Nie Xinzhi , Yang Jun , Wang Li , Zhu Cui , Yang Xuefen , Jiang Zongyong 
Published: September 2022

(1) Background: Deoxynivalenol (DON) is a general mycotoxin that induces severe intestinal barrier injury in humans and animals. Resveratrol (RES) efficiently exerts anti-inflammatory and antioxidant effects. However, the information regarding RES protecting against DON-induced oxidative stress and intestinal inflammation in piglets is limited. (2) Methods: A total of 64 weaned piglets (Duroc × (Landrace × Yorkshire), 21-d-old, barrow) were randomly allocated to four groups (eight replicate pens per group, each pen containing two piglets) for 28 d. The piglets were fed a control diet (CON) or the CON diet supplemented with 300 mg RES/kg diet (RES group), 3.8 mg DON/kg diet (DON) or both (DON+RES) in a 2 × 2 factorial design. (3) Compared with unsupplemented DON-challenged piglets, RES supplementation in DON-challenged piglets increased ileal villus height and the abundance of ileal SOD1, GCLC and PG1-5 transcripts and Muc2 protein (p < 0.05), while decreasing the mRNA and proteins expression of ileal IL-1β, IL-6 and TNF-α, and malondialdehyde (MDA) levels in plasma and ileum in DON-challenged piglets (p < 0.05). Moreover, the abundances of class Bacilli, order Lactobacillales, family Lactobacillaceae and species Lactobacillus gasseri were increased in DON-challenged piglets fed a RES-supplemented diet compared with those in DON-challenged piglets(p ≤ 0.05). (4) Conclusions: our results indicated that RES supplementation in DON-challenged piglets efficiently attenuated intestinal inflammation and oxidative stress and improved gut microbiota, thereby alleviating DON-induced intestinal barrier injury.
SARS-CoV-2 Invasion and Pathological Links to Prion Disease
Authors: Lukiw Walter J. , Jaber Vivian R. , Pogue Aileen I. , Zhao Yuhai 
Published: September 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19 disease, is a highly infectious and transmissible viral pathogen that continues to impact human health globally. Nearly ~600 million people have been infected with SARS-CoV-2, and about half exhibit some degree of continuing health complication, generically referred to as long COVID. Lingering and often serious neurological problems for patients in the post-COVID-19 recovery period include brain fog, behavioral changes, confusion, delirium, deficits in intellect, cognition and memory issues, loss of balance and coordination, problems with vision, visual processing and hallucinations, encephalopathy, encephalitis, neurovascular or cerebrovascular insufficiency, and/or impaired consciousness. Depending upon the patient’s age at the onset of COVID-19 and other factors, up to ~35% of all elderly COVID-19 patients develop a mild-to-severe encephalopathy due to complications arising from a SARS-CoV-2-induced cytokine storm and a surge in cytokine-mediated pro-inflammatory and immune signaling. In fact, this cytokine storm syndrome: (i) appears to predispose aged COVID-19 patients to the development of other neurological complications, especially those who have experienced a more serious grade of COVID-19 infection; (ii) lies along highly interactive and pathological pathways involving SARS-CoV-2 infection that promotes the parallel development and/or intensification of progressive and often lethal neurological conditions, and (iii) is strongly associated with the symptomology, onset, and development of human prion disease (PrD) and other insidious and incurable neurological syndromes. This commentary paper will evaluate some recent peer-reviewed studies in this intriguing area of human SARS-CoV-2-associated neuropathology and will assess how chronic, viral-mediated changes to the brain and CNS contribute to cognitive decline in PrD and other progressive, age-related neurodegenerative disorders.