bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated Pharmacogenetics Analysis of the Three Fangjis Decoctions for Treating Arrhythmias Based on Molecular Network Patterns
Authors: Wei Penglu , Long Dehuai , Tan Yupei , Xing Wenlong , Li Xiang , Yang Kuo , Liu Hongxu 
Published: December 2021

Aim: To explore the diverse target distribution and variable mechanisms of different fangjis prescriptions when treating arrhythmias based on the systems pharmacology.Methods: The active ingredients and their corresponding targets were acquired from the three fangjis [Zhigancao Tang (ZT), Guizhigancao Longgumuli Tang (GLT), and Huanglian E'jiao Tang (HET)] and the arrhythmia-related genes were identified based on comprehensive database screening. Networks were constructed between the fangjis and arrhythmia and used to define arrhythmia modules. Common and differential gene targets were identified within the arrhythmia network modules and the cover rate (CR) matrix was applied to compare the contributions of the fangjis to the network and modules. Comparative pharmacogenetics analyses were then conducted to define the arrhythmia-related signaling pathways regulated by the fangjis prescriptions. Finally, the divergence and convergence points of the arrhythmia pathways were deciphered based on databases and the published literature.Results: A total of 187, 105, and 68 active ingredients and 1,139, 1,195, and 811 corresponding gene targets of the three fangjis were obtained and 102 arrhythmia-related genes were acquired. An arrhythmia network was constructed and subdivided into 4 modules. For the target distribution analysis, 65.4% of genes were regulated by the three fangjis within the arrhythmia network. ZT and GLT were more similar to each other, mainly regulated by module two, whereas HET was divided among all the modules. From the perspective of signal transduction, calcium-related pathways [calcium, cyclic guanosine 3′,5′-monophosphate (cGMP)-PKG, and cyclic adenosine 3′,5′-monophosphate (cAMP)] and endocrine system-related pathways (oxytocin signaling pathway and renin secretion pathways) were associated with all the three fangjis prescriptions. Nevertheless, heterogeneity existed between the biological processes and pathway distribution among the three prescriptions. GLT and HET were particularly inclined toward the conditions involving abnormal hormone secretion, whereas ZT tended toward renin-angiotensin-aldosterone system (RAAS) disorders. However, calcium signaling-related pathways prominently feature in the pharmacological activities of the decoctions. Experimental validation indicated that ZT, GLT, and HET significantly shortened the duration of ventricular arrhythmia (VA) and downregulated the expression of CALM2 and interleukin-6 (IL-6) messenger RNAs (mRNAs); GLT and HET downregulated the expression of CALM1 and NOS3 mRNAs; HET downregulated the expression of CRP mRNA.Conclusion: Comparing the various distributions of the three fangjis, pathways provide evidence with respect to precise applications toward individualized arrhythmia treatments.
Genesis of the Xifeng Low-Temperature Geothermal Field, Guizhou, SW China: Constrains From Geology, Element Geochemistry, and D-O Isotopes
Authors: Li Yanyan , Dor Ji , Zhang Chengjiang , Wang Guiling , Zhang Baojian , Zhang Fangfang , Xing Yifei 
Published: December 2021

The Xifeng geothermal field is located in the Yangtze Craton, SW China, and is one of the most representative low-temperature geothermal fields in China. Widespread thermal anomalies, hot springs, and geothermal wells have been reported by previous studies. However, the nature and forming mechanisms of the field remain poorly understood. Element geochemical (ions, rare earth elements) and stable isotopic (D, O) composition of hot springs, geothermal fluids, rivers, and cold springs from different locations of the Xifeng geothermal field were analyzed in this study. The ions studies revealed that most samples featured the Ca-Mg-HCO3 type, except Xifeng hot springs, and which were characterized by the Ca-Mg-HCO3-SO4 type. Based on quartz geothermometers, the estimated reservoir temperature was 77°C. The results of stable isotopes (D, O) manifest that the Xifeng geothermal system was recharged by meteoric water at an elevation of 1,583 m from SW to NE. The research of rare earth elements (REE) revealed that their accumulation characteristics and obvious positive Eu anomaly were inherited from host feldspar-bearing reservoir dolomites through water-rock interactions. Combined with these observations, geological setting, and previous studies, it was concluded that the formation of the Xifeng geothermal field resulted from recharge, deep circulation, and secondary rising of the meteoric water along the faults. First, meteoric water infiltrated to depth through faults and crack zones. Second, the deep-infiltrated water was heated by radioactive heat, deep heat, and tectonic frictional heat. Finally, as the warmed-up waters underwent considerable deep circulation in the reservoir, it rose again along the main faults, and mixed with groundwater near the surface. Taken together, we suggest that the Xifeng geothermal system should be assigned as a faults-controlling, and deeply circulating meteoric water of low-temperature category.
Relationship of Fat Mass Index and Fat Free Mass Index With Body Mass Index and Association With Function, Cognition and Sarcopenia in Pre-Frail Older Adults
Authors: Merchant Reshma Aziz , Seetharaman Santhosh , Au Lydia , Wong Michael Wai Kit , Wong Beatrix Ling Ling , Tan Li Feng , Chen Matthew Zhixuan , Ng Shu Ee , Soong John Tshon Yit , Hui Richard Jor Yeong , Kwek Sing Cheer , Morley John E. 
Published: December 2021

BackgroundBody mass index (BMI) is an inadequate marker of obesity, and cannot distinguish between fat mass, fat free mass and distribution of adipose tissue. The purpose of this study was twofold. First, to assess cross-sectional relationship of BMI with fat mass index (FMI), fat free mass index (FFMI) and ratio of fat mass to fat free mass (FM/FFM). Second, to study the association of FMI, FFMI and FM/FFM with physical function including sarcopenia, and cognition in pre-frail older adults.MethodsCross-sectional study of 191 pre-frail participants ≥ 65 years, 57.1% females. Data was collected on demographics, cognition [Montreal Cognitive Assessment (MoCA)], function, frailty, calf circumference, handgrip strength (HGS), short physical performance battery (SPPB) and gait speed. Body composition was measured using InBody S10. FMI, FFMI and FM/FFM were classified into tertiles (T1, T2, T3) with T1 classified as lowest and T3 highest tertile respectively and stratified by BMI.ResultsHigher FFMI and lower FM/FFM in the high BMI group were associated with better functional outcomes. Prevalence of low muscle mass was higher in the normal BMI group. FMI and FM/FFM were significantly higher in females and FFMI in males with significant gender differences except for FFMI in ≥ 80 years old. Small calf circumference was significantly less prevalent in the highest tertile of FMI, FM/FMI and FFMI. Prevalence of sarcopenic obesity and low physical function (HGS, gait speed and SPPB scores) were significantly higher in the highest FMI and FM/FFM tertile. Highest FFMI tertile group had higher physical function, higher MoCA scores, lower prevalence of sarcopenic obesity and sarcopenia, After adjustment, highest tertile of FFMI was associated with lower odds of sarcopenia especially in the high BMI group. Highest tertile of FM/FFM was associated with higher odds of sarcopenia. Higher BMI was associated with lower odds of sarcopenia.ConclusionFFMI and FM/FFM may be a better predictor of functional outcomes in pre-frail older adults than BMI. Cut-off values for healthy BMI values and role of calf circumference as a screening tool for sarcopenia need to be validated in larger population. Health promotion intervention should focus on FFMI increment.
Maternal Glucose and LDL-Cholesterol Levels Are Related to Placental Leptin Gene Methylation, and, Together With Nutritional Factors, Largely Explain a Higher Methylation Level Among Ethnic South Asians
Authors: Sletner Line , Moen Aina E. F. , Yajnik Chittaranjan S. , Lekanova Nadezhda , Sommer Christine , Birkeland Kåre I. , Jenum Anne K. , Böttcher Yvonne 
Published: December 2021

BackgroundLeptin, mainly secreted by fat cells, plays a core role in the regulation of appetite and body weight, and has been proposed as a mediator of metabolic programming. During pregnancy leptin is also secreted by the placenta, as well as being a key regulatory cytokine for the development, homeostatic regulation and nutrient transport within the placenta. South Asians have a high burden of type 2 diabetes, partly attributed to a “thin-fat-phenotype”.ObjectiveOur aim was to investigate how maternal ethnicity, adiposity and glucose- and lipid/cholesterol levels in pregnancy are related to placental leptin gene (LEP) DNA methylation.MethodsWe performed DNA methylation analyses of 13 placental LEP CpG sites in 40 ethnic Europeans and 40 ethnic South Asians participating in the STORK-Groruddalen cohort.ResultsSouth Asian ethnicity and gestational diabetes (GDM) were associated with higher placental LEP methylation. The largest ethnic difference was found for CpG11 [5.8% (95% CI: 2.4, 9.2), p&lt;0.001], and the strongest associations with GDM was seen for CpG5 [5.2% (1.4, 9.0), p=0.008]. Higher maternal LDL-cholesterol was associated with lower placental LEP methylation, in particular for CpG11 [-3.6% (-5.5, -1.4) per one mmol/L increase in LDL, p&lt;0.001]. After adjustments, including for nutritional factors involved in the one-carbon-metabolism cycle (vitamin D, B12 and folate levels), ethnic differences in placental LEP methylation were strongly attenuated, while associations with glucose and LDL-cholesterol persisted.ConclusionsMaternal glucose and lipid metabolism is related to placental LEP methylation, whilst metabolic and nutritional factors largely explain a higher methylation level among ethnic South Asians.
Experimental Study on Stratification Morphology of the Molten Pool During Severe Accident
Authors: Li Yang , Gong Houjun , Hu Yunwen , Yang Shengxing , Li Yong , Zan Yuanfeng 
Published: December 2021

Stratification morphology of a molten pool under severe reactor accident was investigated by the CESEF experimental facility. The experimental scale was 5,000 g, the atomic ratio of U/Zr was 1.5, the content of stainless steel was 10%, and the oxidation degree of Zr was 40–100%. It was shown that the molten pool was obviously stratified within the range of experimental parameters; one was a metal layer, and the other was an oxide layer. The layered morphology of the molten pool was different with the composition of different corium. With the decrease in the Zr oxidation degree, the metal layer moved downward in the molten pool, and the molten pool would overturn. The main elements in the oxide layer were U, Zr, and O, and the content of stainless steel was low. The main element in the metal layer was stainless steel and contained a certain amount of U and Zr.
Pre-Digested Protein Enteral Nutritional Supplementation Enhances Recovery of CD4+ T Cells and Repair of Intestinal Barrier in HIV-Infected Immunological Non-Responders
Authors: Geng Shi-Tao , Zhang Jian-Bo , Wang Yue-Xin , Xu Yu , Lu Danfeng , Zhang Zunyue , Gao Ju , Wang Kun-Hua , Kuang Yi-Qun 
Published: December 2021

AIDS patients with immune non-response are prone to malnutrition, intestinal barrier damage, thus aggravating chronic immune activation and inflammation. However, nutritional interventions targeting malnutrition may be beneficial to restore immune function, improve clinical outcomes, and reduce mortality remains largely unclear. This work aimed to evaluate the efficacy of a nutritional supplement in HIV-infected immune non-responders (INRs). The subjects received oral supplementation of a pre-digested protein nutrition formula for three months. We show that the CD4+T and CD8+T cell counts were significantly increased after supplementation of the pre-digested enteral nutritional supplement. Among all pro-inflammatory cytokines in the serum, only IL-1β level was significantly decreased, while TNF-β was significantly increased (P&lt; 0.05). The levels of intestinal mucosal damage markers, diamine oxidase (DAO), D-lactic acid (D-lactate), and lipopolysaccharide (LPS), decreased significantly (P&lt; 0.05) after the nutritional intervention. Moreover, at month 3 after the intervention, the body weight, body mass index, albumin, and hemoglobin of all subjects were significantly increased (P &lt; 0.05). The correlation analysis demonstrated a significantly negative correlation of CD4+T cell count with levels of DAO (r = -0.343,P= 0.004), D-lactate (r = -0.250,P= 0.037), respectively, and a significantly positive correlation of IL-1β level with levels of DAO (r = 0.445,P&lt; 0.001), D-lactate (r = 0.523,P&lt; 0.001), and LPS (r = 0.622,P&lt; 0.001). We conclude that the pre-digested enteral nutrition supplement is effective for HIV-infected INRs.
The Alternative Complement Pathway Is Activated Without a Corresponding Terminal Pathway Activation in Patients With Heart Failure
Authors: Holt Margrethe Flesvig , Michelsen Annika E. , Shahini Negar , Bjørkelund Elisabeth , Bendz Christina Holt , Massey Richard J. , Schjalm Camilla , Halvorsen Bente , Broch Kaspar , Ueland Thor , Gullestad Lars , Nilsson Per H. , Aukrust Pål , Mollnes Tom Eirik , Louwe Mieke C. 
Published: December 2021

ObjectiveDysregulation of the complement system has been described in patients with heart failure (HF). However, data on the alternative pathway are scarce and it is unknown if levels of factor B (FB) and the C3 convertase C3bBbP are elevated in these patients. We hypothesized that plasma levels of FB and C3bBbP would be associated with disease severity and survival in patients with HF.MethodsWe analyzed plasma levels of FB, C3bBbP, and terminal C5b-9 complement complex (TCC) in 343 HF patients and 27 healthy controls.ResultsCompared with controls, patients with HF had elevated levels of circulating FB (1.6-fold, p &lt; 0.001) and C3bBbP (1.3-fold, p &lt; 0.001). In contrast, TCC, reflecting the terminal pathway, was not significantly increased (p = 0.15 vs controls). FB was associated with NT-proBNP, troponin, eGFR, and i.e., C-reactive protein. FB, C3bBbP and TCC were not associated with mortality in HF during a mean follow up of 4.3 years.ConclusionOur findings suggest that in patients with HF, the alternative pathway is activated. However, this is not accompanied by activation of the terminal pathway.
Association of Prescription With Body Composition and Patient Outcomes in Incident Peritoneal Dialysis Patients
Authors: Verger Christian , Ronco Claudio , Van Biesen Wim , Heaf James , Vrtovsnik François , Vera Rivera Manel , Puide Ilze , Azar Raymond , Gauly Adelheid , Atiye Saynab , De los Ríos Tatiana 
Published: December 2021

Objective: The nutritional status of patients on peritoneal dialysis (PD) is influenced by patient- and disease-related factors and lifestyle. This analysis evaluated the association of PD prescription with body composition and patient outcomes in the prospective incident Initiative for Patient Outcomes in Dialysis–Peritoneal Dialysis (IPOD-PD) patient cohort.Design and Methods: In this observational, international cohort study with longitudinal follow-up of 1,054 incident PD patients, the association of PD prescription with body composition was analyzed by using the linear mixed models, and the association of body composition with death and change to hemodialysis (HD) by means of a competing risk analysis combined with a spline analysis. Body composition was regularly assessed with the body composition monitor, a device applying bioimpedance spectroscopy.Results: Age, time on PD, and the use of hypertonic and polyglucose solutions were significantly associated with a decrease in lean tissue index (LTI) and an increase in fat tissue index (FTI) over time. Competing risk analysis revealed a U-shaped association of body mass index (BMI) with the subdistributional hazard ratio (HR) for risk of death. High LTI was associated with a lower subdistributional HR, whereas low LTI was associated with an increased subdistributional HR when compared with the median LTI as a reference. High FTI was associated with a higher subdistributional HR when compared with the median as a reference. Subdistributional HR for risk of change to HD was not associated with any of the body composition parameters. The use of polyglucose or hypertonic PD solutions was predictive of an increased probability of change to HD, and the use of biocompatible solutions was predictive of a decreased probability of change to HD.Conclusion: Body composition is associated with non-modifiable patient-specific and modifiable treatment-related factors. The association between lean tissue and fat tissue mass and death and change to HD in patients on PD suggests developing interventions and patient counseling to improve nutritional markers and, ultimately, patient outcomes.Study Registration: The study has been registered at Clinicaltrials.gov (NCT01285726).
Development and Validation of a Nomogram Incorporating Colloid Osmotic Pressure for Predicting Mortality in Critically Ill Neurological Patients
Authors: Lv Bo , Hu Linhui , Fang Heng , Sun Dayong , Hou Yating , Deng Jia , Zhang Huidan , Xu Jing , He Linling , Liang Yufan , Chen Chunbo 
Published: December 2021

Backgrounds: The plasma colloid osmotic pressure (COP) values for predicting mortality are not well-estimated. A user-friendly nomogram could predict mortality by incorporating clinical factors and scoring systems to facilitate physicians modify decision-making when caring for patients with serious neurological conditions.Methods: Patients were prospectively recruited from March 2017 to September 2018 from a tertiary hospital to establish the development cohort for the internal test of the nomogram, while patients recruited from October 2018 to June 2019 from another tertiary hospital prospectively constituted the validation cohort for the external validation of the nomogram. A multivariate logistic regression analysis was performed in the development cohort using a backward stepwise method to determine the best-fit model for the nomogram. The nomogram was subsequently validated in an independent external validation cohort for discrimination and calibration. A decision-curve analysis was also performed to evaluate the net benefit of the insertion decision using the nomogram.Results: A total of 280 patients were enrolled in the development cohort, of whom 42 (15.0%) died, whereas 237 patients were enrolled in the validation cohort, of which 43 (18.1%) died. COP, neurological pathogenesis and Acute Physiology and Chronic Health Evaluation II (APACHE II) score were predictors in the prediction nomogram. The derived cohort demonstrated good discriminative ability, and the area under the receiver operating characteristic curve (AUC) was 0.895 [95% confidence interval (CI), 0.840–0.951], showing good correction ability. The application of this nomogram to the validation cohort also provided good discrimination, with an AUC of 0.934 (95% CI, 0.892–0.976) and good calibration. The decision-curve analysis of this nomogram showed a better net benefit.Conclusions : A prediction nomogram incorporating COP, neurological pathogenesis and APACHE II score could be convenient in predicting mortality for critically ill neurological patients.
Wound Vitality in Decomposed Bodies: New Frontiers Through Immunohistochemistry
Authors: Bertozzi Giuseppe , Ferrara Michela , La Russa Raffaele , Pollice Giovanni , Gurgoglione Giovanni , Frisoni Paolo , Alfieri Letizia , De Simone Stefania , Neri Margherita , Cipolloni Luigi 
Published: December 2021

Background: The question about wound vitality and the estimation of wound age of production are two of the classic investigation fields of forensic sciences. To answer this, the techniques most frequently used in research studies are immunohistochemistry (IHC), molecular biology, and biochemistry. Despite the great data on the literature about the usefulness of IHC in forensic pathology, there is always a request for further studies, especially on tissues altered by putrefactive phenomena. In fact, the degradation of the tissues is intended as the main limiting factor to the use of this technique.Scope: The aim of this pilot study was to evaluate the immunohistochemical behavior of samples collected from decomposed bodies (in different putrefaction phases) and to relate these findings to wound vitality and postmortem interval.Materials and Methods: Samples of skin and soft tissues were collected during autopsies, which were executed on decomposed bodies, whose cause of death was concluded to be traumatic. An immunohistochemical study was performed using antibodies against CD15, CD45, IL-15, tryptase, and glycophorin-A MMPs (endopeptidases involved in degrading extracellular matrix proteins: MMP-9 and MMP-2). An immunohistochemistry (IHC) reaction was evaluated according to a qualitative method as the following legend: (0): not expressed, (+): isolated and disseminated expression, (++): expression in groups or widespread foci, and (+++): widespread expression.Results: Most of the tested markers (tryptase, glycophorin, IL15, CD 15, CD 45, and MMP9) showed to be highly expressed in the tissue of putrefied skin for 15 days.Discussion and Conclusion: Although certainly inconclusive, this experimental application demonstrated that a nonexclusive but combined use of multiple antibodies is appropriate to verify wound vitality in decomposed bodies. Among them, GPA exhibited major reliability.