bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vascular homeostasis in atherosclerosis: A holistic overview
Authors: Xu Suowen , Lyu Qing Rex , Ilyas Iqra , Tian Xiao-Yu , Weng Jianping 
Published: September 2022

Atherosclerosis refers to the deposition of lipids and the co-existence of inflammation and impaired inflammation resolution in pan-vasculature, which causes lumen narrowing, hardening, plaque formation, and the manifestation of acute cardiovascular events. Emerging evidence has suggested that vascular circulation can be viewed as a complex homeostatic system analogous to a mini-ecosystem which consists of the vascular microenvironment (niche) and the crosstalk among phenotypically and functionally diverse vascular cell types. Here, we elucidate how cell components in the vascular wall affect vascular homeostasis, structure, function, and atherosclerosis in a holistic perspective. Finally, we discuss the potential role of vascular-stabilizing strategies including pharmacotherapies, natural substances and lifestyle modifications, in preventing cardiovascular diseases by preserving vascular integrity and homeostasis.
Factors associated with the recurrence of choroidal neovascularization in pathologic myopia
Authors: Jing Ruixia , Bo Yuxia , Gao Lei , Wang Zhen 
Published: September 2022

PurposeTo investigate the factors associated with the recurrence of pathologic myopia choroidal neovascularization (PM-CNV).MethodsForty-eight eyes of 48 patients with PM-CNV treated with conbercept at least 6 months of follow-up were included. Appearance of ellipsoid zone (EZ) and retinal pigment epithelium (RPE) observed on optical coherence tomography (OCT). Hyperreflective foci (HRF) height measured on OCT. Observation of CNV shape on OCT-angiography (OCTA). PM-CNV area measured on OCTA. To observe relationship between these factors and best corrected visual acuity (BCVA) and PM-CNV recurrence.ResultsThe 48 patients (48 eyes) with PM-CNV were divided into two groups: yielding a group of 20 eyes with type 1 and a group of 28 eyes with type 2. The BCVA of type 1 was better than type 2 before and after treatment (P &lt; 0.005). Smaller HRF height (P &lt; 0.001) and CNV area (P &lt; 0.001) for type 1 than type 2. The appearance of EZ and RPE were intact (P &lt; 0.001). Spearman correlation analysis found that final BCVA was significantly associated with baseline BCVA, HRF height, and appearance of EZ (P &lt; 0.05). Binary logistics regression analysis revealed that PM-CNV recurrence was significantly correlated not only HRF height and CNV area, but also with appearance of EZ, and RPE (P &lt; 0.05).ConclusionPM-CNV had a higher recurrence ratio. Baseline BCVA and clinical features play an important role for vision prognosis. Factors associated with PM-CNV recurrence include HRF height, CNV area, and changes in EZ and RPE structure.
Awake prone positioning for patients with COVID-19 pneumonia in intensive care unit: A systematic review and meta-analysis
Authors: Huang Hui-Bin , Yao Yan , Zhu Yi-Bing , Du Bin 
Published: September 2022

BackgroundAwake prone positioning (APP) has been widely used in non-intubated COVID-19 patients during the pandemic. However, high-quality evidence to support its use in severe COVID-19 patients in an intensive care unit (ICU) is inadequate. Therefore, we aimed to assess the efficacy and safety of APP for intubation requirements and other important outcomes in this patient population.MethodsWe searched for potentially relevant articles in PubMed, Embase, and the Cochrane database from inception to May 25, 2022. Studies focusing on COVID-19 adults in ICU who received APP compared to controls were included. The primary outcome was the intubation requirement. Secondary outcomes were mortality, ICU stay, and adverse events. Study quality was independently assessed, and we also conducted subgroup analysis, sensitivity analysis, and publication bias to explore the potential influence factors.ResultsTen randomized controlled trials with 1,686 patients were eligible. The quality of the included studies was low to moderate. Overall, the intubation rate was 35.2% in the included patients. The mean daily APP duration ranged from &lt;6 to 9 h, with poor adherence to APP protocols. When pooling, APP significantly reduced intubation requirement (risk ratio [RR] 0.84; 95%CI, 0.74–0.95; I2 = 0%, P = 0.007). Subgroup analyses confirmed the reduced intubation rates in patients who were older (≥60 years), obese, came from a high mortality risk population (&gt;20%), received HFNC/NIV, had lower SpO2/FiO2 (&lt;150 mmHg), or undergone longer duration of APP (≥8 h). However, APP showed no beneficial effect on mortality (RR 0.92 [95% CI 0.77–1.10; I2 = 0%, P = 0.37] and length of ICU stay (mean difference = −0.58 days; 95% CI, −2.49 to 1.32; I2 = 63%; P = 0.55).ConclusionAPP significantly reduced intubation requirements in ICU patients with COVID-19 pneumonia without affecting the outcomes of mortality and ICU stay. Further studies with better APP protocol adherence will be needed to define the subgroup of patients most likely to benefit from this strategy.
Allosteric regulation of substrate channeling: Salmonella typhimurium tryptophan synthase
Authors: Ghosh Rittik K. , Hilario Eduardo , Chang Chia-en A. , Mueller Leonard J. , Dunn Michael F. 
Published: September 2022

The regulation of the synthesis of L-tryptophan (L-Trp) in enteric bacteria begins at the level of gene expression where the cellular concentration of L-Trp tightly controls expression of the five enzymes of the Trp operon responsible for the synthesis of L-Trp. Two of these enzymes, trpA and trpB, form an αββα bienzyme complex, designated as tryptophan synthase (TS). TS carries out the last two enzymatic processes comprising the synthesis of L-Trp. The TS α-subunits catalyze the cleavage of 3-indole D-glyceraldehyde 3′-phosphate to indole and D-glyceraldehyde 3-phosphate; the pyridoxal phosphate-requiring β-subunits catalyze a nine-step reaction sequence to replace the L-Ser hydroxyl by indole giving L-Trp and a water molecule. Within αβ dimeric units of the αββα bienzyme complex, the common intermediate indole is channeled from the α site to the β site via an interconnecting 25 Å-long tunnel. The TS system provides an unusual example of allosteric control wherein the structures of the nine different covalent intermediates along the β-reaction catalytic path and substrate binding to the α-site provide the allosteric triggers for switching the αββα system between the open (T) and closed (R) allosteric states. This triggering provides a linkage that couples the allosteric conformational coordinate to the covalent chemical reaction coordinates at the α- and β-sites. This coupling drives the α- and β-sites between T and R conformations to achieve regulation of substrate binding and/or product release, modulation of the α- and β-site catalytic activities, prevention of indole escape from the confines of the active sites and the interconnecting tunnel, and synchronization of the α- and β-site catalytic activities. Here we review recent advances in the understanding of the relationships between structure, function, and allosteric regulation of the complex found in Salmonella typhimurium.
Release of protein N-glycans by effectors of a Hofmann carboxamide rearrangement
Authors: Kasim Mumtaz , Schulz Malissa , Griebel Anja , Malhotra Akshay , Müller Barbara , von Horsten Hans Henning 
Published: September 2022

Background: Chemical methods for glycan release have gained traction because of their cost efficiency, accelerated reaction time and ability to release glycans not amenable to enzymatic cleavage. Oxidative chemical glycan release via hypochlorite treatment has been shown to be a convenient and efficient method that yields N-glycans similar to classical PNGase F digestion. We observed that the initial steps of the suggested mechanism for the oxidative release of glycans from glycoproteins by hypohalites showed similarities to the initiating steps of the classical Hofmann rearrangement of carboxamides. Therefore, we investigated the ability of different stable effectors of a Hofmann-type carboxamide rearrangement to efficiently and selectively release N-glycans from glycoproteins.Methods: Released glycans obtained from different experimental chemical release approaches were analyzed by HILIC-FLD, BHZ-FACE and ESI-MS and evaluated with respect to electrophoretic mobility, retention time and integrated peak area for resolved glycans.Results: We show that the known Hoffmann catalysts 1,3-dichloro-5,5-dimethylhydantoin, the hypervalent organoiodine (III) compound diacetoxy-iodobenzene as well as in-situ hypobromite generation using Oxone® and potassium bromide are all capable of releasing protein-bound N-glycans in good yield. Among the compounds investigated, diacetoxy-iodobenzene was capable of releasing glycans in the absence of alkali. Detailed investigations of the bromide/Oxone® method revealed a dependence of N-glycan release efficiency from the temporal order of bromide addition to the reaction mix as well as from a molar excess of bromide over Oxone®. Conclusions. These findings suggest that the oxidative release of N-glycans occurs via the initiating steps of a Hofmann carboxamide rearrangement. Hypervalent organoiodine compounds hold the promise of releasing glycans in the absence of alkali. The in-situ generation of hypobromite by bromide/Oxone® produces a consistent defined amount of reagent for rapid N-glycan release for both analytical and preparative purposes.
Associations between abdominal obesity and the risk of stroke in Chinese older patients with obstructive sleep apnea: Is there an obesity paradox?
Authors: Su Xiaofeng , Li Kailiang , Yang Ling , Yang Yang , Gao Yinghui , Gao Yan , Guo JingJing , Lin Junling , Chen Kaibing , Han Jiming , Liu Lin 
Published: September 2022

Background and purposeAbdominal obesity (AO) is a well-known independent risk factor for stroke in the general population although it remains unclear in the case of the elderly, especially in Chinese older patients with obstructive sleep apnea (OSA), considering the obesity paradox. This study aimed to investigate the association between AO and stroke among Chinese older patients with OSA.MethodsData were collected from January 2015 to October 2017, and 1,290 older patients (age 60–96 years) with OSA (apnea–hypopnea index ≥ 5 events/h on polysomnography) were consecutively enrolled from sleep centers at six hospitals, evaluated for AO defined as waist circumference (WC) using the standardized criteria for the Chinese population, and followed up prospectively for a median period of 42 months. Logistic regression and Cox regression analyses were used to determine the cross-sectional and longitudinal associations between AO and stroke risk in these participants and different groups of the severity of OSA.ResultsParticipants with AO had a higher prevalence of stroke at baseline. A higher incidence of stroke during a median follow-up period of 42 months in participants with AO than in participants without AO (12.4% vs. 6.8% and 8.3% vs. 2.4%, respectively; both P &lt; 0.05) was predicted. Cross-sectional analysis revealed an association between AO and stroke (odds ratio [OR]1.96, 95% confidence interval [CI] 1.31–2.91), which was stronger among participants with moderate OSA only (OR 2.16, 95%CI 1.05–4.43). Cox regression analysis showed that, compared to participants without AO, participants with AO had a higher cumulative incidence of stroke (hazard ratio [HR] 2.16, 95% CI 1.12–4.04) during a median follow-up of 42 months, and this association was observed in patients with severe OSA only (HR 3.67, 95% CI 1.41–9.87) but not for individuals with mild OSA (HR = 1.84, 95% CI 0.43–6.23) and moderate OSA (HR = 1.98, 95% CI 0.73–6.45).ConclusionThe risk of stroke is associated with AO among Chinese older patients who have OSA, both at baseline and during follow-up, and the strength of the association varied by OSA severity. Active surveillance for early detection of AO could facilitate the implementation of stroke-preventive interventions in the Chinese older OSA population.
Self-reported and genetically predicted effects of coffee intake on rheumatoid arthritis: Epidemiological studies and Mendelian randomization analysis
Authors: Pu Bin , Gu Peng , Zheng ChuRong , Ma LiQiong , Zheng XiaoHui , Zeng ZhanPeng 
Published: September 2022

Background and aimsCausal research concerning coffee intake and rheumatoid arthritis (RA) risk is controversial. The objective of this study was to further explore the causal relationship between coffee intake and RA risk.MethodsThe 4,310 participants from NHANES 2003–2006 were included in an epidemiological study to assess the association between coffee intake and RA by weighted multivariate logistic regression. The inverse variance weighted (IVW) method of two-sample Mendelian randomization (MR), employing genetic data from UK Biobank (428,860 cases) of coffee intake and MR-Base platform (14,361 cases and 43,923 controls) of RA, was performed to estimate the causal relationship between coffee intake and RA.ResultsWeighted multivariate logistic regression suggested no significant correlation between coffee intake and RA. Compared to the no-coffee group, the odds ratio for RA in the &lt;1, 1–3, ≥4 cups/day group were 1.297, 1.378, and 1.125 (P= 0.204, 0.098, and 0.698, respectively). In the IVW of MR analysis, there was no causal relationship between coffee intake and RA (OR = 1.47,P= 0.218).ConclusionOur study did not support a causal association between coffee intake and RA risk. However, it is necessary to consider valid information on coffee intake, including brewing method, type of coffee, and quantity, in further analysis of coffee intake and RA.
Association between socioeconomic positions and overweight/obesity in rural Nepal
Authors: Bhattarai Sanju , Nerhus Larsen Rikke , Shrestha Archana , Karmacharya Biraj , Sen Abhijit 
Published: September 2022

IntroductionObesity and its association with socioeconomic factors are well-established. However, the gradient of this relationship among rural populations in low- and middle-income countries such as Nepal is not fully understood. We sought to assess the association of socioeconomic factors (education, income, and employment status) with overweight/obesity.MethodsThis cross-sectional study analyzed data from 260 participants aged ≥18 years and attending a rural health center in Dolakha, Nepal. Self-reported data on demographic, socioeconomic, and lifestyle factors was collected, and weight and height were measured for all the study participants. Those with a body mass index of &lt;25 kg/m2 were regarded as non-overweight/obese and those with ≥25 kg/m2 were regarded as overweight/obese. Poisson regression models were used to estimate prevalence ratios and corresponding 95% confidence intervals to assess the association between socioeconomic factors and overweight/obesity. In addition, we assessed the effect of modification by age and gender to study the effect of socioeconomic factors on overweight/obesity.ResultsThe age-standardized prevalence of overweight/obesity was higher for individuals with higher education (23%) and high-income (32%) and those who were unemployed (42%). Compared to the low-income and no formal education groups, the prevalence ratio of overweight/ obesity was 1.69 and 2.27 times more for those belonging to the high-income and high school and above groups, respectively. No evidence of effect modification by gender and age was observed.ConclusionsSocioeconomic factors, education, and income were positively associated with overweight/obesity prevalence in rural Nepal. Further large studies using longitudinal settings are necessary to replicate our findings.
Invasive ductal breast cancer molecular subtype prediction by MRI radiomic and clinical features based on machine learning
Authors: Sheng Weiyong , Xia Shouli , Wang Yaru , Yan Lizhao , Ke Songqing , Mellisa Evelyn , Gong Fen , Zheng Yun , Tang Tiansheng 
Published: September 2022

BackgroundMost studies of molecular subtype prediction in breast cancer were mainly based on two-dimensional MRI images, the predictive value of three-dimensional volumetric features from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for predicting breast cancer molecular subtypes has not been thoroughly investigated. This study aimed to look into the role of features derived from DCE-MRI and how they could be combined with clinical data to predict invasive ductal breast cancer molecular subtypes.MethodsFrom January 2019 to December 2021, 190 Chinese women with invasive ductal breast cancer were studied (32 triple-negative, 59 HER2-enriched, and 99 luminal lesions) in this institutional review board-approved retrospective cohort study. The image processing software extracted 1130 quantitative radiomic features from the segmented lesion area, including shape-based, first-order statistical, texture, and wavelet features. Three binary classifications of the subtypes were performed: triple-negative vs. non-triple-negative, HER2-overexpressed vs. non-HER2-overexpressed, and luminal (A + B) vs. non-luminal. For the classification, five machine learning methods (random forest, logistic regression, support vector machine, naïve Bayes, and eXtreme Gradient Boosting) were employed. The classifiers were chosen using the least absolute shrinkage and selection operator method. The area evaluated classification performance under the receiver operating characteristic curve, sensitivity, specificity, accuracy, F1-Score, false positive rate, precision, and geometric mean.ResultsEXtreme Gradient Boosting model showed the best performance in luminal and non-luminal groups, with AUC, sensitivity, specificity, accuracy, F1-Score, false positive rate, precision, and geometric mean of 0.8282, 0.7524, 0.6542, 0.6964, 0.6086, 0.3458, 0.8524 and 0.7016, respectively. Meanwhile, the random forest model showed the best performance in HER2-overexpressed and non-HER2-overexpressed groups, with AUC, sensitivity, specificity, accuracy, F1-Score, false positive rate, precision, and geometric mean of 0.8054, 0.2941, 0.9744, 0.7679, 0.4348, 0.0256, 0.8333 and 0.5353, respectively. Furthermore, eXtreme Gradient Boosting model showed the best performance in the triple-negative and non-triple-negative groups, with AUC, sensitivity, specificity, accuracy, F1-Score, false positive rate, precision, and geometric mean of 0.9031, 0.9362, 0.4444, 0.8571, 0.9167, 0.5556, 0.8980 and 0.6450.ConclusionClinical data and three-dimension imaging features from DCE-MRI were identified as potential biomarkers for distinguishing between three molecular subtypes of invasive ductal carcinomas breast cancer. In the future, more extensive studies will be required to evaluate the findings.
Elucidating the mechanism behind and investigating the efficacy of Traditional Chinese Medicine and Traditional Tibetan Medicine in combination with standard therapeutics in hepatocellular carcinoma and cholangiocarcinoma in vitro
Authors: Suo Huizhen , Hochnadel Inga , Petriv Nataliia , Franke Raimo , Schmidt Jennifer , Limanska Nataliia , Tugai Alisa , Jedicke Nils , Broenstrup Mark , Manns Michael P. , Yevsa Tetyana 
Published: September 2022

In this study, we investigated compounds of plant and mushroom origin belonging to Traditional Chinese Medicine (TCM) and to Traditional Tibetan Medicine (TTM): a sandy beige mushroom Trametes robiniophila Murr, commonly known as Huaier/TCM as well as Ershiwuwei Songshi Wan and Qiwei Honghua Shusheng Wan, which both belong to TTM. We aimed to study the efficacy of TTM and TCM in hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) in vitro. TCM and TTM were tested either as a monotherapy, or in combination with standard therapeutics: sorafenib for HCC treatment and gemcitabine for CCA. We also discovered a protective mechanism behind the most successful therapeutic combinations. The results demonstrated that TCM and TTM inhibited the proliferation of cancer cells in a time- and dose-dependent manner. The results were compared to classical chemotherapeutics currently used in the clinic: sorafenib for HCC and gemcitabine for CCA. In HCC settings, a combination of Huaier (16 mg/ml) with half of the human plasma concentration of sorafenib, Qiwei Honghua Shusheng Wan (1 mg/ml) monotherapy as well as its combination with half or even a quarter dose of the human plasma concentration of sorafenib represented the most efficient treatments, inhibiting the growth of HCC cells more effectively than the standard therapy. The inhibitory mechanism relied on a strong induction of apoptosis. In CCA settings, Ershiwuwei Songshi Wan and Qiwei Honghua Shusheng Wan as monotherapies or in combination with very low doses of gemcitabine inhibited the growth of CCA cells more efficiently than the standard therapy. Importantly, Ershiwuwei Songshi Wan at the 8 and 16 mg/ml concentrations and Qiwei Honghua Shusheng Wan at the 4 mg/ml concentration were efficacious with gemcitabine applied at massively reduced concentrations. The protective mechanism in CCA relied on a strong induction of early and late apoptosis. Cellular senescence and necroptosis were not associated with protection against HCC/CCA. Combination therapy with TCM or TTM allowed for a dose reduction of standard chemotherapeutics. This is especially important as both chemotherapeutic drugs show strong side effects in patients. The reduction of chemotherapeutics and the synergistic effect observed while applying them in combination with TCM and TTM has strong perspectives for the clinic and patients suffering from HCC and CCA.
Pharmacokinetics of immediate and sustained-release formulations of paroxetine: Population pharmacokinetic approach to guide paroxetine personalized therapy in chinese psychotic patients
Authors: Li Xiao-lin , Huang Shan-qing , Xiao Tao , Wang Xi-pei , Kong Wan , Liu Shu-jing , Zhang Zi , Yang Ye , Huang Shan-shan , Ni Xiao-jia , Lu Hao-yang , Zhang Ming , Wen Yu-guan , Shang De-wei 
Published: September 2022

Paroxetine is one of the most potent selective serotonin reuptake inhibitors (SSRIs) approved for treating depression, panic disorder, and obsessive-compulsive disorder. There is evidence linking genetic polymorphisms and nonlinear metabolism to the Paroxetine’s pharmacokinetic (PK) variability. The purpose of the present study was to develop a population PK (PPK) model of paroxetine in Chinese patients, which was used to define the paroxetine’s PK parameters and quantify the effect of clinical and baseline demographic factors on these PK characteristics. The study included 184 inpatients with psychosis (103 females and 81 males), with a total of 372 serum concentrations of paroxetine for PPK analyses. The total daily dosage ranged from 20 to 75 mg. One compartment model could fit the PKs characterize of paroxetine. Covariate analysis revealed that dose, formulation, and sex had a significant effect on the PK parameters of paroxetine; however, there was no evident genetic influence of CYP2D6 enzymes on paroxetine concentrations in Chinese patients. The study determined that the population’s apparent distribution volume (V/F) and apparent clearance (CL/F), respectively, were 8850 and 21.2 L/h. The CL/F decreased 1-2-fold for each 10 mg dose increase, whereas the different formulations caused a decrease in V/F of 66.6%. Sex was found to affect bioavailability (F), which decreased F by 47.5%. Females had higher F values than males. This PPK model described data from patients with psychosis who received paroxetine immediate-release tablets (IR-T) and/or sustained-release tablets (SR-T). Paroxetine trough concentrations and relative bioavailability were different between formulations and sex. The altered serum concentrations of paroxetine resulting from individual variants and additive effects need to be considered, to optimize the dosage regimen for individual patients.