bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased residual cardiovascular risk in U.S. veterans with moderately-elevated baseline triglycerides and well-controlled LDL-C levels on statins
Authors: Leatherman Sarah , Ferguson Ryan , Hau Cynthia , Harrington Kelly , Granowitz Craig , Philip Sephy , Toth Peter Paul , Bhatt Deepak , Boden William 
Published: November 2022

BackgroundRecent studies have demonstrated a causal role for elevated triglycerides (TG) in incident cardiovascular (CV) events in patients with established coronary heart disease (CHD) and those with CV risk factors alone, particularly diabetes.ObjectiveUsing a large cohort of U.S. veterans with statin-controlled LDL-C levels (40–100 mg/dL), we explored residual CV risk among patients with elevated baseline TG levels (150–499 mg/dL) vs. those with normal TG levels (&lt;150 mg/dL).MethodsWe identified veterans receiving a statin but not a TG-lowering agent from the VA electronic health records database, from 2010 to 2015. We compared composite CV event rates (MI, stroke, unstable angina, coronary revascularization, and CV death) between the elevated TG and normal TG groups. We stratified the study cohort according to 3 CV risk groups: (1) no diabetes and no prior CV event, (2) diabetes and no prior CV event, and (3) prior CV event. We calculated crude event rates, rate ratios, and event rate ratios adjusted for age, sex, systolic blood pressure, estimated glomerular filtration rate, and weight.ResultsThe cohort included 396,189 veterans (predominantly male and white) of whom 109,195 (28%) had elevated TG levels. Those with elevated TG were younger (age 73 vs. 77 years) and had a higher body mass index (31.3 vs. 28.3 Kg/M2). The overall composite crude and adjusted rate ratios comparing the elevated and normal TG groups were 1.10 (1.09, 1.12) and 1.05 (1.03, 1.06), respectively. For CV risk groups 1, 2 and 3, the adjusted rate ratios comparing the elevated and normal TG groups were 0.99 (0.96, 1.02), 1.05 (1.02, 1.08), and 1.07 (1.04, 1.10), respectively. An association of increased rate ratios did not hold for fatal events.ConclusionThose with elevated TG levels and well-controlled LDL-C on statins showed a modest increase in CV events compared to those with normal TG. Elevated TG levels were associated with increased CV events in patients with established CV disease and with diabetes only, suggesting that elevated TG levels are associated with a similar degree of residual risk in high-risk primary prevention and secondary prevention settings.
Relationships of circulating CD4+ T cell subsets and cytokines with the risk of relapse in patients with Crohn’s disease
Authors: Duclaux-Loras Rémi , Boschetti Gilles , Flourie Bernard , Roblin Xavier , Leluduec Jean-Benoit , Paul Stéphane , Almeras Thibaut , Ruel Karine , Buisson Anthony , Bienvenu Jacques , Josson Cendrine , Jasnowski Renaud , Legastelois Stéphane , Foussat Arnaud , Meunier Camille , Viret Christophe , Rozieres Aurore , Faure Mathias , Kaiserlian Dominique , Nancey Stéphane 
Published: November 2022

Background and aimsWe aimed to analyze circulating CD4+T cell subsets and cytokines during the course of Crohn’s disease (CD).Methods and resultsCD4+T cell subsets, ultrasensitive C-reactive protein (usCRP), and various serum cytokines (IL-6, IL-8, IL-10, IL-13, IL-17A, IL-23, TNFα, IFNγ, and TGFβ) were prospectively monitored every 3 months for 1 year, using multicolor flow cytometry and an ultrasensitive Erenna method in CD patients in remission at inclusion. Relapse occurred in 35 out of the 113 consecutive patients (31%). For patients in remission within 4 months prior to relapse and at the time of relapse, there was no significant difference in Th1, Th17, Treg, and double-positive CD4+T cell subsets co-expressing either IFNγ and FOXP3, IL-17A and FOXP3, or IFNγ and IL-17A. On the contrary, in patients who remained in remission, the mean frequency and number of double-positive IL-17A+FOXP3+CD4+T cells and the level of usCRP were significantly higher (p≤ 0.01) 1 to 4 months prior to relapse. At the time of relapse, only the IL-6 and usCRP levels were significantly higher (p≤ 0.001) compared with those patients in remission. On multivariate analysis, a high number of double-positive IL-17A+FOXP3+CD4+T cells (≥1.4 cells/mm3) and elevated serum usCRP (≥3.44 mg/L) were two independent factors associated with risk of relapse.ConclusionsDetection of circulating double-positive FOXP3+IL-17A+CD4+T cell subsets supports that T cell plasticity may reflect the inflammatory context of Crohn’s disease. Whether this subset contributes to the pathogenesis of CD relapse needs further studies.
Electroencephalography spectral edge frequency and suppression rate-guided sedation in patients with COVID-19: A randomized controlled trial
Authors: Tobar Eduardo , Farías José I. , Rojas Verónica , Penna Antonello , Egaña José I. , Ponce Daniela , Bravo Daniela , Maldonado Felipe , Gajardo Abraham , Gutiérrez Rodrigo 
Published: November 2022

BackgroundSedation in coronavirus disease 2019 (COVID-19) patients has been identified as a major challenge. We aimed to investigate whether the use of a multiparameter electroencephalogram (EEG) protocol to guide sedation in COVID-19 patients would increase the 30-day mechanical ventilation-free days (VFD).MethodsWe conducted a double-blind randomized clinical trial. We included patients with severe pneumonia due to COVID-19 who required mechanical ventilation (MV) and deep sedation. We randomized to the control (n = 25) or multiparameter group (n = 25). Sedation in the intervention group was administered following the standard institutional protocols together with a flow chart designed to reduce the propofol administration dose if the EEG suppression rate was over 2% or the spectral edge frequency 95 (SEF95) was below 10 Hz. We performed an intention-to-treat analysis to evaluate our primary outcome (30-day VFD).ResultsThere was no difference in VFD at day 30 (median: 11 [IQR 0–20] days in the control group vs. 0 [IQR 0–21] days in the BIS multiparameter group, p = 0.87). Among secondary outcomes, we documented a 17% reduction in the total adjusted propofol administered during the first 5 days of the protocol [median: 2.3 (IQR 1.9–2.8) mg/k/h in the control group vs. 1.9(IQR 1.5–2.2) mg/k/h in the MP group, p = 0.005]. This was accompanied by a higher average BIS value in the intervention group throughout the treatment period.ConclusionA sedation protocol guided by multivariate EEG-derived parameters did not increase the 30-day VFD. However, the intervention led to a reduction in total propofol administration.
Incidence, predictors, and outcomes of early hospital readmissions after kidney transplantation: Systemic review and meta-analysis
Authors: Iqbal Kinza , Hasanain Muhammad , Rathore Sawai Singh , Iqbal Ayman , Kazmi Syeda Kanza , Yasmin Farah , Koritala Thoyaja , Thongprayoon Charat , Surani Salim 
Published: November 2022

BackgroundEarly hospital readmission (EHR) within 30 days after kidney transplantation is a significant quality indicator of transplant centers and patient care. This meta-analysis aims to evaluate the incidence, predictors, and outcomes of EHR after kidney transplantation.MethodsWe comprehensively searched the databases, including PubMed, Cochrane CENTRAL, and Embase, from inception until December 2021 to identify studies that assessed incidence, risk factors, and outcome of EHR. The outcomes included death-censored graft failure and mortality. Data from each study were combined using the random effect to calculate the pooled incidence, mean difference (MD), odds ratio (OR), and hazard ratio (HR) with 95% confidence interval (CI).ResultsA total of 17 studies were included. The pooled EHR incidence after kidney transplant was 24.4% (95% CI 21.7–27.3). Meta-analysis showed that recipient characteristics, including older recipient age (MD 2.05; 95% CI 0.90–3.20), Black race (OR 1.31; 95% CI 1.11, 1.55), diabetes (OR 1.32; 95% CI 1.22–1.43), and longer dialysis duration (MD 0.85; 95% CI 0.41, 1.29), donor characteristics, including older donor age (MD 2.02; 95% CI 0.93–3.11), and transplant characteristics, including delayed graft function (OR 1.75; 95% CI 1.42–2.16) and longer length of hospital stay during transplantation (MD 1.93; 95% CI 0.59–3.27), were significantly associated with the increased risk of EHR. EHR was significantly associated with the increased risk of death-censored graft failure (HR 1.70; 95% CI 1.43–2.02) and mortality (HR 1.46; 95% CI 1.27–1.67) within the first year after transplantation.ConclusionAlmost one-fourth of kidney transplant recipients had EHR within 30 days after transplant, and they had worse post-transplant outcomes. Several risk factors for EHR were identified. This calls for future research to develop and implement for management strategies to reduce EHR in high-risk patients.
Non-contrast and contrast enhanced computed tomography radiomics in preoperative discrimination of lung invasive and non-invasive adenocarcinoma
Authors: Sun Yingli , Zhao Wei , Kuang Kaiming , Jin Liang , Gao Pan , Duan Shaofeng , Xiao Yi , Liu Jun , Li Ming 
Published: November 2022

ObjectiveThis study aimed to assess the value of radiomics based on non-contrast computed tomography (NCCT) and contrast-enhanced computed tomography (CECT) images in the preoperative discrimination between lung invasive adenocarcinomas (IAC) and non-invasive adenocarcinomas (non-IAC).MethodsWe enrolled 1,185 pulmonary nodules (478 non-IACs and 707 IACs) to build and validate radiomics models. An external testing set comprising 63 pulmonary nodules was collected to verify the generalization of the models. Radiomic features were extracted from both NCCT and CECT images. The predictive performance of radiomics models in the validation and external testing sets were evaluated and compared with radiologists’ evaluations. The predictive performances of the radiomics models were also compared between three subgroups in the validation set (Group 1: solid nodules, Group 2: part-solid nodules, and Group 3: pure ground-glass nodules).ResultsThe NCCT, CECT, and combined models showed good ability to discriminate between IAC and non-IAC [respective areas under the curve (AUCs): validation set = 0.91, 0.90, and 0.91; Group 1 = 0.82, 0.79, and 0.81; Group 2 = 0.93, 0.92, and 0.93; and Group 3 = 0.90, 0.90, and 0.89]. In the external testing set, the AUC of the three models were 0.89, 0.91, and 0.89, respectively. The accuracies of these three models were comparable to those of the senior radiologist and better those that of the junior radiologist.ConclusionRadiomic models based on CT images showed good predictive performance in discriminating between lung IAC and non-IAC, especially in part solid nodule group. However, radiomics based on CECT images provided no additional value compared to NCCT images.
Clinicopathological differences of high Fusobacterium nucleatum levels in colorectal cancer: A review and meta-analysis
Authors: Wang Yi , Wen Yuting , Wang Jiayin , Lai Xin , Xu Ying , Zhang Xuanping , Zhu Xiaoyan , Ruan Chenglin , Huang Yao 
Published: November 2022

ObjectiveTo systematically evaluate the significance of Fusobacterium nucleatum (Fn) levels the clinicopathological impacts of cancer.MethodsLiterature from Pubmed, Embase, and Web of Science was retrieved to collect all English literatures on the correlation between Fn and cancer, and the quality of literatures collected was assessed based on the Newcastle-Ottawa Quality Assessment Scale. The heterogeneity and sensitivity were detected by Stata 14.0 software, and the correlation between Fn and cancer clinicopathological as the effect variables was assessed according to the odds ratio (OR) and 95% confidence interval (CI). The forest plot was drawn.ResultsA total of 19 articles meeting the inclusion criteria were selected. The incidence of Fn prevalence varied considerably (range: 6.1 to 83.3%) and was greater than 10% in 13 of 19 studies. Compared with those with no/low Fn levels, the high levels of Fn was positively associated with vascular invasion, nerve invasion, depth of invasion, and distant metastasis [vascular invasion: OR = 1.66, 95%CI(1.07, 2.57), I2 = 21.9%, fixed effect model; nerve invasion: OR = 1.36, 95%CI(1.00, 1.84), I2 = 43.1%, fixed effect model; infiltration depth: OR = 1.94, 95%CI(1.20, 3.15), I2 = 67.2%, random effect model; distant metastasis: OR = 1.80, 95%CI(1.23, 2.64), I2 = 3.4%, fixed effect model]. Patients with MLH1 methylation always present a higher Fn levels than those without methylation [OR = 2.53, 95%CI(1.42, 4.53), P = 0.01, I2 = 57.5%, random effect model]. Further, Fn was associatedwith the molecular characteristics of cancers [MSI-H Vs. MSS/MSI-low: OR = 2.92, 95%CI(1.61, 5.32), P = 0.01, I2 = 63.2%, random effect model; High Vs. Low/Negative CIMP: OR = 2.23, 95%CI(1.64, 3.03), P = 0.01, I2 = 64.2%, random effect model; KRAS mutation Vs. wild-type: OR = 1.24, 95%CI(1.04, 1.48), P = 0.02, I2 = 27.0%, fixed effect model; Present Vs. Abscent BRAF mutations: OR = 1.88, 95%CI(1.44, 2.45), P = 0.01, I2 = 24.2%, fixed effect model]. The cancer patients with high levels of Fn often have worse RFS than those with no/low Fn levels[OR = 1.14, 95%CI(0.61, 1.68), P = 0.01, I2 = 80.7%, random effect model].ConclusionThis review and meta-analysis showed that Fn could be used to predict unfavorable prognosis and function as potential prognostic biomarkers in colorectal cancer (CRC). Our data may have implications for targeting Fn to develop strategies for cancer prevention and treatment.
Altered cortical thickness, degree centrality, and functional connectivity in middle-age type 2 diabetes mellitus
Authors: Kang Shangyu , Chen Yuna , Wu Jinjian , Liang Yi , Rao Yawen , Yue Xiaomei , Lyu Wenjiao , Li Yifan , Tan Xin , Huang Haoming , Qiu Shijun 
Published: November 2022

PurposeThis study aimed to investigate the changes in brain structure and function in middle-aged patients with type 2 diabetes mellitus (T2DM) using morphometry and blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI).MethodsA total of 44 middle-aged patients with T2DM and 45 matched healthy controls (HCs) were recruited. Surface-based morphometry (SBM) was used to evaluate the changes in brain morphology. Degree centrality (DC) and functional connectivity (FC) were used to evaluate the changes in brain function.ResultsCompared with HCs, middle-aged patients with T2DM exhibited cortical thickness reductions in the left pars opercularis, left transverse temporal, and right superior temporal gyri. Decreased DC values were observed in the cuneus and precuneus in T2DM. Hub-based FC analysis of these regions revealed lower connectivity in the bilateral hippocampus and parahippocampal gyrus, left precuneus, as well as left frontal sup.ConclusionCortical thickness, degree centrality, as well as functional connectivity were found to have significant changes in middle-aged patients with T2DM. Our observations provide potential evidence from neuroimaging for analysis to examine diabetes-related brain damage.
Performance in information processing speed is associated with parietal white matter tract integrity in multiple sclerosis
Authors: Grothe Matthias , Jochem Katharina , Strauss Sebastian , Langner Sönke , Kirsch Michael , Hoffeld Kai , Penner Iris Katharina , Nagels Guy , Klepzig Kai , Domin Martin , Lotze Martin 
Published: November 2022

BackgroundThe Symbol Digit Modalities Test (SDMT) is most frequently used to test processing speed in patients with multiple sclerosis (MS). Functional imaging studies emphasize the importance of frontal and parietal areas for task performance, but the influence of frontoparietal tracts has not been thoroughly studied. We were interested in tract-specific characteristics and their association with processing speed in MS patients.MethodsDiffusion tensor imaging was obtained in 100 MS patients and 24 healthy matched controls to compare seed-based tract characteristics descending from the superior parietal lobule [Brodman area 7A (BA7A)], atlas-based tract characteristics from the superior longitudinal fasciculus (SLF), and control tract characteristics from the corticospinal tract (CST) and their respective association with ability on the SDMT.ResultsPatients had decreased performance on the SDMT and decreased white matter volume (each p &lt; 0.05). The mean fractional anisotropy (FA) for the BA7A tract and CST (p &lt; 0.05), but not the SLF, differed between MS patients and controls. Furthermore, only the FA of the SLF was positively associated with SDMT performance even after exclusion of the lesions within the tract (r = 0.25, p &lt; 0.05). However, only disease disability and total white matter volume were associated with information processing speed in a linear regression model.ConclusionsProcessing speed in MS is associated with the structural integrity of frontoparietal white matter tracts.
Ameliorative effect of vanillin on scopolamine-induced dementia-like cognitive impairment in a mouse model
Authors: Anand Abhinav , Khurana Navneet , Ali Nemat , AlAsmari Abdullah F. , Alharbi Metab , Waseem Mohammad , Sharma Neha 
Published: November 2022

BackgroundAlzheimer’s disease (AD) is the most common form of dementia, which is among the top five causes of death in the United States. It is a neurodegenerative disorder that causes permanent loss of memory and cognition. The current pharmacotherapy for AD is based on providing symptomatic relief only and has many side effects. There is a need for a safer, disease-modifying drug for the treatment of AD.Experimental approachThe PASS online software was used to screen phytoconstituents based on their predicted effects on various AD-related targets. Vanillin was selected as the compound of interest, as it has not been researched elaborately on any animal model of AD. The acetylcholinesterase inhibitory activity of vanillin was established in vitro. Thereafter, ameliorative effect of vanillin was evaluated using the exteroceptive memory model in scopolamine-induced cognitive impairment mice model.ResultsVanillin showed an acetylcholinesterase inhibitory activity in vitro, and the IC50 value was calculated to be 0.033 mM. Vanillin significantly reversed the memory and behavioral deficits caused by scopolamine as demonstrated by significant improvement in memory in negative reinforcement, elevated plus maze, and spatial learning paradigms. Vanillin also proved to have a nootropic effect. Also, vanillin proved to have significantly better antioxidant and acetylcholinesterase inhibitory effects in vivo than donepezil hydrochloride. The potential anti-AD activity of vanillin was also confirmed by the reduction in IL-6 levels and TNF-α levels.ConclusionOur results suggest that vanillin is a safe and effective natural drug candidate having a great potential for the treatment of AD. However, more research is required to evaluate its effect on A beta plaques and Tau neurofibrillary tangles in vivo.
Associations between maternal adiposity and appetite-regulating hormones in human milk are mediated through maternal circulating concentrations and might affect infant outcomes
Authors: Christensen Sophie Hilario , Lewis Jack Ivor , Larnkjær Anni , Frøkiær Hanne , Allen Lindsay H. , Mølgaard Christian , Michaelsen Kim F. 
Published: November 2022

BackgroundAppetite-regulating hormones (ARH) in human milk (HM) are suggested to affect infants’ milk intake and possibly infant growth. Maternal adiposity might contribute to higher levels of ARH in HM, either from the mammary gland or from raised circulating levels due to higher adiposity. Counterfactual-based mediation analysis can define indirect and direct effects between HM ARH and maternal and infant factors, and might be an important tool when investigating the mother-milk-infant triad.ObjectiveWe aim to investigate whether potential associations between (1) maternal adiposity and HM ARH and (2) HM ARH and infant milk intake and growth are mediated through maternal and infant plasma ARH, respectively.Materials and methodsMaternal and infant anthropometry and body composition, HM and blood samples were collected from 223 mother-infant dyads participating in the Mother, Infant and Lactation Quality study at three postpartum visits from 1 to 8.49 months. Leptin, insulin and adiponectin were analyzed using immunoassays. Mediation analyses using linear mixed-effect models were applied to investigate the direct and indirect effects through maternal and infant plasma hormone concentrations.ResultsA positive association between maternal body-mass-index (BMI) and HM leptin was mediated by maternal plasma leptin by 29% when fixing BMI to &lt; 25 kg/m2, and through 51% when fixing BMI to ≥ 25 kg/m2 (pinteraction &lt; 0.01). There was no mediated effect through plasma insulin in the association between BMI and HM insulin (p = 0.068). We found negative and positive associations between HM insulin and total milk intake and infant weight, respectively, however, these diminished in mediation analyses with reduced sample sizes.ConclusionOur main results suggest that the association between maternal adiposity and HM leptin was mediated through circulating leptin to a stronger degree for mothers with overweight compared to mothers with normal-weight. This indicates that excess maternal adiposity, and the resulting rise of circulating leptin and possible concomitant low-grade inflammation, may be reflected in HM composition.Clinical trials registry numberNCT03254329.
PD0166285 sensitizes esophageal squamous cell carcinoma to radiotherapy by dual inhibition of WEE1 and PKMYT1
Authors: Zhang Qingyi , Lin Xu , Jiang Kan , Deng Jun , Ke Lei , Wu Ziheng , Xia Pinghui , Li Qi , Yu Li , Ni Pengzhi , Lv Wang , Hu Jian 
Published: November 2022

BackgroundEsophageal squamous cell carcinoma (ESCC) is an aggressive tumor with a 5-year survival rate of only 20%. More than 80% of ESCC patients possess TP53 mutation, which abolishes the G1/S checkpoint and accelerates the cell cycle. Thus, WEE1 and PKMYT1, regulators of G2/M phase in cell cycle, play essential roles in TP53-mutated cancer cells. PD0166285(PD) is a pyridopyrimidine compound that can inhibit WEE1 and PKMYT1 simultaneously, however, the effects of PD on ESCC, either as monotherapy or in combination therapy with radiotherapy, remain unclear.MethodsTo measure the anti-tumor efficacy of PD in ESCC cells, cell viability, cell cycle and cell apoptosis assays were examined in KYSE150 and TE1 cells with PD treatment. The combination therapy of PD and irradiation was also performed in ESCC cells to find whether PD can sensitize ESCC cells to irradiation. Vivo assays were also performed to investigate the efficacy of PD.ResultsWe found that the IC50 values of PD among ESCC cells ranged from 234 to 694 nM, PD can regulate cell cycle and induce cell apoptosis in ESCC cells in a dose-dependent manner. When combined with irradiation, PD sensitized ESCC cells to irradiation by abolishing G2/M phase arrest, inducing a high ratio of mitosis catastrophe, eventually leading to cell death. We also demonstrated that PD can attenuate DNA damage repair by inhibiting Rad51, further research also found the interaction of WEE1 and Rad51. In vivo assays, PD inhibited the tumor growth in mice, combination therapy showed better therapeutic efficacy.ConclusionPD0166285 can exert antitumor effect by inhibiting the function of WEE1 and PKMYT1 in ESCC cells, and also sensitize ESCC cells to irradiation not only by abolishing G2/M arrest but also attenuating DNA repair directly. We believe PD0166285 can be a potent treatment option for ESCC in the future.