bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hair Cortisol Concentration, Weight Loss Maintenance and Body Weight Variability: A Prospective Study Based on Data From the European NoHoW Trial
Authors: Larsen Sofus C. , Turicchi Jake , Christensen Gitte L. , Larsen Charlotte S. , Jørgensen Niklas R. , Mikkelsen Marie-Louise K. , Horgan Graham , O’Driscoll Ruairi , Michalowska Joanna , Duarte Cristiana , Scott Sarah E. , Santos Inês , Encantado Jorge , Palmeira Antonio L. , Stubbs R. James , Heitmann Berit L. 
Published: September 2021

Several cross-sectional studies have shown hair cortisol concentration to be associated with adiposity, but the relationship between hair cortisol concentration and longitudinal changes in measures of adiposity are largely unknown. We included 786 adults from the NoHoW trial, who had achieved a successful weight loss of ≥5% and had a body mass index of ≥25 kg/m2 prior to losing weight. Hair cortisol concentration (pg/mg hair) was measured at baseline and after 12 months. Body weight and body fat percentage were measured at baseline, 6-month, 12-month and 18-month visits. Participants weighed themselves at home ≥2 weekly using a Wi-Fi scale for the 18-month study duration, from which body weight variability was estimated using linear and non-linear approaches. Regression models were conducted to examine log hair cortisol concentration and change in log hair cortisol concentration as predictors of changes in body weight, change in body fat percentage and body weight variability. After adjustment for lifestyle and demographic factors, no associations between baseline log hair cortisol concentration and outcome measures were observed. Similar results were seen when analysing the association between 12-month concurrent development in log hair cortisol concentration and outcomes. However, an initial 12-month increase in log hair cortisol concentration was associated with a higher subsequent body weight variability between month 12 and 18, based on deviations from a nonlinear trend (β: 0.02% per unit increase in log hair cortisol concentration [95% CI: 0.00, 0.04]; P=0.016). Our data suggest that an association between hair cortisol concentration and subsequent change in body weight or body fat percentage is absent or marginal, but that an increase in hair cortisol concentration during a 12-month weight loss maintenance effort may predict a slightly higher subsequent 6-months body weight variability.Clinical Trial RegistrationISRCTN registry, identifier ISRCTN88405328.
High Carbon Load in Food Processing Industrial Wastewater is a Driver for Metabolic Competition in Aerobic Granular Sludge
Authors: Paulo Ana M. S. , Amorim Catarina L. , Costa Joana , Mesquita Daniela P. , Ferreira Eugénio C. , Castro Paula M. L. 
Published: September 2021

Aerobic granular sludge (AGS) processes are among the most robust wastewater treatments. One of their greatest advantages is related to the granules multi-layered structure, which creates a protective barrier against organic shock loads and variable wastewater composition, particularly attractive for the treatment of industrial wastewater. However, when treating a wastewater with variable and complex composition, the difficulty in identifying factors that most affect a specific biological process increases. In this study, the effect of organic loading rate (OLR), namely carbon content, on nitrification in an AGS process treating fish canning wastewater was investigated. Besides process performance, also biomass structural changes, and microbial community composition were analysed. Reactor operation lasted for 107 days and was divided in three phases during which different OLR and C/N ratios were applied. A higher OLR was applied during the first two phases (ca. 1.1 and 1.5 kg COD m−3 day−1, respectively) compared to the third phase (between 0.12 and 0.78 kg COD m−3 day−1) and the C/N ratios also varied (ca. 4.4, 7.8, and 2.9, respectively). Throughout the operation, COD concentration in the outlet was lower than 100 mg O2 L−1. Nitrification was inhibited during the second phase and recovered afterwards. Principal component analysis (PCA) of quantitative image analysis (QIA) and performance data allowed to distinguish process changes over the three operational phases. During the first two phases, the decrease in the biomass robustness occurred, but recovered during the last phase, indicating that the high content of organic matter had possibly an effect on the aerobic granules structural characteristics. The composition of the AGS microbiome did not change substantially after the end of the higher OLR periods. The main microbial diversity shifts were mostly associated to adaptation to higher or lower carbon availability. Bacteria and inferred enzymes associated to nitrogen and phosphorous removal were identified. Chryseobacterium, a bacterium with high metabolic versatility, was able to adapt to the organic shock load, becoming dominant over operation. Despite the variable composition of the fish canning wastewater, carbon was identified as the main driver for nitrification inhibition, while promoting changes in the physical characteristics and on the microbial community of granules.
A Founder Pathogenic Variant of PPIB Unique to Chinese Population Causes Osteogenesis Imperfecta IX
Authors: Zhu Wenting , Yan Kai , Chen Xijing , Zhao Wei , Wu Yiqing , Tang Huanna , Chen Ming , Wu Jian , Wang Pengpeng , Zhang Runju , Shen Yiping , Zhang Dan 
Published: September 2021

Background: Osteogenesis imperfecta (OI) is a heterogeneous genetic disorder characterized by bone fragility. PPIB pathogenic variants cause a perinatal lethal form of OI type IX. A limited number of pathogenic variants have been reported so far worldwide.Methods: We identified a rare pedigree whose phenotype was highly consistent with OI-IX. Exome sequencing was performed to uncover the causal variants. The variant pathogenicity was classified following the ACMG/AMP guidelines. The founder effect and the age of the variant were assessed.Results: We identified a homozygous missense variant c.509G &gt; A/p.G170D in PPIB in an affected fetus. This variant is a Chinese-specific allele and can now be classified as pathogenic. We estimated the allele frequency (AF) of this variant to be 0.0000427 in a Chinese cohort involving 128,781 individuals. All patients and carriers shared a common haplotype, indicative of a founder effect. The estimated age of variant was 65,160 years. We further identified pathogenic variants of PPIB in gnomAD and ClinVar databases, the conserved estimation of OI type IX incidence to be 1/1,000,000 in Chinese population.Conclusion: We reported a founder pathogenic variant in PPIB specific to the Chinese population. We further provided our initial estimation of OI-IX disease incidence in China.
CD4+ T Cell Dependent B Cell Recovery and Function After Autologous Hematopoietic Stem Cell Transplantation
Authors: Heck Clarissa , Steiner Sophie , Kaebisch Eva M. , Frentsch Marco , Wittenbecher Friedrich , Scheibenbogen Carmen , Hanitsch Leif G. , Nogai Axel , le Coutre Philipp , Bullinger Lars , Blau Igor-Wolfgang , Na Il-Kang 
Published: September 2021

IntroductionHigh-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) represents a standard treatment regime for multiple myeloma (MM) patients. Common and potentially fatal side effects after auto-HSCT are infections due to a severely compromised immune system with hampered humoral and cellular immunity. This study delineates in depth the quantitative and functional B cell defects and investigates underlying extrinsic or intrinsic drivers.MethodsPeripheral blood of MM patients undergoing high-dose chemotherapy and auto-HSCT (before high-dose chemotherapy and in early reconstitution after HSCT) was studied. Absolute numbers and distribution of B cell subsets were analyzedex vivousing flow cytometry. Additionally, B cell function was assessed with T cell dependent (TD) and T cell independent (TI) stimulation assays, analyzing proliferation and differentiation of B cells by flow cytometry and numbers of immunoglobulin secreting cells in ELISpots.ResultsQuantitative B cell defects including a shift in the B cell subset distribution occurred after auto-HSCT. Functionally, these patients showed an impaired TD as well as TI B cell immune response. Individual functional responses correlated with quantitative alterations of CD19+, CD4+, memory B cells and marginal zone-like B cells. The TD B cell function could be partially restored upon stimulation with CD40L/IL-21, successfully inducing B cell proliferation and differentiation into plasmablasts and immunoglobulin secreting cells.ConclusionQuantitative and functional B cell defects contribute to the compromised immune defense in MM patients undergoing auto-HSCT. Functional recovery upon TD stimulation and correlation with CD4+ T cell numbers, indicate these as extrinsic drivers of the functional B cell defect. Observed correlations of CD4+, CD19+, memory B and MZ-like B cell numbers with the B cell function suggest that these markers should be tested as potential biomarkers in prospective studies.
Predictive Value of Geriatric Nutritional Risk Index in Patients With Coronary Artery Disease: A Meta-Analysis
Authors: Fan Yu , He Lian , Zhou Yongjing , Man Changfeng 
Published: September 2021

Background:Low Geriatric Nutritional Risk Index has been identified as an index of impaired nutritional state. The objective of the meta-analysis was to assess the association of the Geriatric Nutritional Risk Index (GNRI) with adverse outcomes in patients with coronary artery disease (CAD).Methods:Relevant studies were identified by comprehensively searching PubMed and Embase databases in May 2021. Studies assessing the association of GNRI with all-cause mortality or major adverse cardiovascular events (MACEs) in patients with CAD were included. The predictive value of GNRI was summarized by pooling multivariable adjusted risk ratios (RR) with 95% confidence intervals (CI) per GNRI point decrease or the lowest vs. the highest GNRI group.Results:A total of eight studies involving 9277 patients with CAD were analyzed. Meta-analysis showed that the lowest GNRI was associated with a higher risk of all-cause mortality (RR 2.10; 95% CI 1.68–2.63) and MACEs (RR 2.84; 95% CI 1.56–5.16), respectively. Furthermore, per point decrease in GNRI was associated with 8 and 10% additional risk of all-cause mortality and MACEs. Subgroup analysis indicated that the value of low GNRI in predicting all-cause mortality was not affected by subtype of patients or follow-up duration.Conclusion:Low GNRI score at baseline was associated with a higher risk of all-cause mortality and cardiovascular events in patients with CAD. The nutritional state estimated by the GNRI score could provide important predictive information in patients with CAD.
Machine Learning-Based CT Radiomics Analysis for Prognostic Prediction in Metastatic Non-Small Cell Lung Cancer Patients With EGFR-T790M Mutation Receiving Third-Generation EGFR-TKI Osimertinib Treatment
Authors: Tang Xin , Li Yuan , Yan Wei-feng , Qian Wen-lei , Pang Tong , Gong You-ling , Yang Zhi-gang 
Published: September 2021

Background and PurposeAs a third-generation EGFR tyrosine kinase inhibitor (TKI), osimertinib is approved for treating advanced non-small cell lung cancer (NSCLC) patients with EGFR-T790M mutation after progression on first- or second-generation EGFR-TKIs such as gefitinib, erlotinib and afatinib. We aim at exploring the feasibility and effectiveness of using radiomic features from chest CT scan to predict the prognosis of metastatic non-small cell lung cancer (NSCLC) patients with EGFR-T790M mutation receiving second-line osimertinib therapy.MethodsContrast-enhanced and unenhanced chest CT images before osimertinib treatment were collected from 201 and 273 metastatic NSCLC patients with EGFR-T790M mutation, respectively. Radiomic features were extracted from the volume of interest. LASSO regression was used to preliminarily evaluate the prognostic values of different radiomic features. We then performed machine learning-based analyses including random forest (RF), support vector machine (SVM), stepwise regression (SR) and LASSO regression with 5-fold cross-validation (CV) to establish the optimal radiomic model for predicting the progression-free survival (PFS) of osimertinib treatment. Finally, a combined clinical-radiomic model was developed and validated using the concordance index (C-index), decision-curve analysis (DCA) and calibration curve analysis.ResultsDisease progression occurred in 174/273 (63.7%) cases. CT morphological features had no ability in predicting patients’ prognosis in osimertinib treatment. Univariate COX regression followed by LASSO regression analyses identified 23 and 6 radiomic features from the contrast-enhanced and unenhanced CT with prognostic value, respectively. The 23 contrast-enhanced radiomic features were further used to construct radiomic models using different machine learning strategies. Radiomic model built by SR exhibited superior predictive accuracy than RF, SVR or LASSO model (mean C-index of the 5-fold CV: 0.660 vs. 0.560 vs. 0.598 vs. 0.590). Adding the SR radiomic model to the clinical model could remarkably strengthen the C-index of the latter from 0.672 to 0.755. DCA and calibration curve analyses also demonstrated good performance of the combined clinical-radiomic model.ConclusionsRadiomic features extracted from the contrast-enhanced chest CT could be used to evaluate metastatic NSCLC patients’ prognosis in osimertinib treatment. Prognostic models combing both radiomic features and clinical factors had a great performance in predicting patients’ outcomes.
Ginsenoside Rb1 Produces Antidepressant-Like Effects in a Chronic Social Defeat Stress Model of Depression Through the BDNF–Trkb Signaling Pathway
Authors: Jiang Ning , Huang Hong , Zhang Yiwen , Lv Jingwei , Wang Qiong , He Qinghu , Liu Xinmin 
Published: September 2021

Ginsenoside Rb1 (Rb1), an important bioactive ingredient of Panax ginseng, has potent neuroprotective effects. The objective of the study is to elucidate the impact of Rb1 treatment on chronic social defeat stress (CSDS)–induced depressive-like behaviors and its related mechanism. According to the obtained results, the daily oral administration of Rb1 (35 and 70 mg/kg) and imipramine (15 mg/kg) for 28 days significantly reversed the social avoidance behavior, anhedonia, and behavioral despair via CSDS exposure, as demonstrated by the considerable elevation in the time in the zone in the social interaction test, consumption of sucrose solution in the sucrose preference test, and decrease in immobility time in the forced swim test. Moreover, Rb1 obviously restored the CSDS-induced decrease in the BDNF signaling pathway and hippocampal neurogenesis. Rb1 significantly increased the hippocampal levels of ERK, AKT, and CREB phosphorylation and increased the number of DCX+ cells in DG. Importantly, the antidepressant effects of Rb1 were completely blocked in mice by using K252a (the nonselective tyrosine kinase B inhibitor). In conclusion, our results indicated that Rb1 exerts promising antidepressant-like effects in mice with CSDS-induced depression, and its effects were facilitated by enhancing the BDNF signaling cascade and upregulation of hippocampal neurogenesis.
Optimization of Pichia pastoris Expression System for High-Level Production of Margatoxin
Authors: Naseem Muhammad Umair , Tajti Gabor , Gaspar Attila , Szanto Tibor G. , Borrego Jesús , Panyi Gyorgy 
Published: September 2021

Margatoxin (MgTx) is a high-affinity blocker of voltage-gated potassium (Kv) channels. It inhibits Kv1.1–Kv1.3 ion channels in picomolar concentrations. This toxin is widely used to study physiological function of Kv ion channels in various cell types, including immune cells. Isolation of native MgTx in large quantities from scorpion venom is not affordable. Chemical synthesis and recombinant production in Escherichia coli need in vitro oxidative refolding for proper disulfide bond formation, resulting in a very low yield of peptide production. The Pichia pastoris expression system offers an economical approach to overcome all these limitations and gives a higher yield of correctly refolded recombinant peptides. In this study, improved heterologous expression of recombinant MgTx (rMgTx) in P. pastoris was obtained by using preferential codons, selecting the hyper-resistant clone against Zeocin, and optimizing the culturing conditions. About 36 ± 4 mg/L of &gt;98% pure His-tagged rMgTx (TrMgTx) was produced, which is a threefold higher yield than has been previously reported. Proteolytic digestion of TrMgTx with factor Xa generated untagged rMgTx (UrMgTx). Both TrMgTx and UrMgTx blocked the Kv1.2 and Kv1.3 currents (patch-clamp) (Kd for Kv1.2 were 64 and 14 pM, and for Kv1.3, 86 and 50 pM, respectively) with comparable potency to the native MgTx. The analysis of the binding kinetics showed that TrMgTx had a lower association rate than UrMgTx for both Kv1.2 and Kv1.3. The dissociation rate of both the analogues was the same for Kv1.3. However, in the case of Kv1.2, TrMgTx showed a much higher dissociation rate with full recovery of the block than UrMgTx. Moreover, in a biological functional assay, both peptides significantly downregulated the expression of early activation markers IL2R and CD40L in activated CD4+ TEM lymphocytes whose activation was Kv1.3 dependent. In conclusion, the authors report that the Pichia expression system is a powerful method to produce disulfide-rich peptides, the overexpression of which could be enhanced noticeably through optimization strategies, making it more cost-effective. Since the presence of the His-tag on rMgTx only mildly altered the block equilibrium and binding kinetics, recombinant toxins could be used in ion channel research without removing the tag and could thus reduce the cost and time demand for toxin production.
Negative Hydrogen Ion Sources for Fusion: From Plasma Generation to Beam Properties
Authors: Fantz U. , Briefi S. , Heiler A. , Wimmer C. , Wünderlich D. 
Published: September 2021

The neutral beam injection systems for the international fusion experiment ITER used for heating, current drive, and diagnostic purposes are based on RF-driven negative hydrogen ion sources with a source area of roughly 0.9 m × 1.9 m. The sources operate at 0.3 Pa in hydrogen and in deuterium using a total available RF generator power of 800 kW per source at a frequency of 1 MHz. In order to fulfill the challenging requirements for ITER and beyond (like a DEMOnstration power plant, DEMO), worldwide developments are underway addressing the topics of plasma generation, ion extraction together with the issue of reducing and stabilizing the co-extracted electron current, and the beam properties. At the example of the activities at the ITER prototype source and the size scaling experiment ELISE, the present status and its challenges are summarized. The RF power transfer efficiency of these sources is only about 65% in maximum, giving significant room for improvements to relax the demands on the RF generator and ensure reliable operation. The plasma uniformity in front of the large extraction system is the result of plasma drifts. They have a huge impact on the nonuniformity of the co-extracted electrons and influence the ions and thus the beam properties as well. Understanding the optics of such large beams composed of hundreds of beamlets is a crucial task and is under continuous improvement. The main challenge, however, is still the fulfillment of the ITER requirements for deuterium, in particular, for long pulses. The management of caesium, which is evaporated into the source to generate sufficient negative ions by the surface conversion process, is one of the keys for stable and reliable operation.
Thermoregulatory and Metabolic Demands of Naval Special Warfare Divers During a 6-h Cold-Water Training Dive
Authors: Chapin Andrea C. , Arrington Laura J. , Bernards Jake R. , Kelly Karen R. 
Published: September 2021

Introduction: Extreme environmental conditions induce changes in metabolic rate and substrate use due to thermoregulation. Cold-water full-body submersion for extended periods of time is inevitable for training and missions carried out by Naval Special Warfare divers. Anthropometric, physiologic, and metabolic data have been reported from partial immersion in cold water in non-thermally protected men; data is limited in thermally protected divers in extremely cold water. Thermoregulatory and metabolic demands during prolonged cold-water submersion in Naval Special Warfare divers are unknown.Objective: Assess thermoregulatory and metabolic demands of Naval Special Warfare divers surrounding prolonged cold-water submersion.Materials and Methods: Sixteen active-duty U.S. Navy Sea Air and Land (SEAL) operators tasked with cold-water dive training participated. Divers donned standard military special operations diving equipment and fully submerged to a depth of ∼ 6 m in a pool chilled to 5°C for a 6-h live training exercise. Metabolic measurements were obtained via indirect calorimetry for 10-min pre-dive and 5-min post dive. Heart rate, skin temperature, and core temperature were measured throughout the dive.Results: Core temperature was maintained at the end of the 6-h dive, 36.8 ± 0.4°C and was not correlated to body composition (body fat percentage, lean body mass) or metabolic rate. SEALs were not at risk for non-freezing cold injuries as mean skin temperature was 28.5 ± 1.6°C at end of the 6-h dive. Metabolic rate (kcal/min) was different pre- to post-dive, increasing from 1.9 ± 0.2 kcal/min to 2.8 ± 0.2 kcal/min, p &lt; 0.001, 95% CI [0.8, 1.3], Cohen’s d effect size 2.3. Post-dive substrate utilization was 57.5% carbohydrate, 0.40 ± 0.16 g/min, and 42.5% fat, 0.13 ± 0.04 g/min.Conclusion: Wetsuits supported effective thermoprotection in conjunction with increase in thermogenesis during a 6-h full submersion dive in 5°C. Core temperature was preserved with an expected decrease in skin temperature. Sustained cold-water diving resulted in a 53% increase in energy expenditure. While all participants increased thermogenesis, there was high inter-individual variability in metabolic rate and substrate utilization. Variability in metabolic demands may be attributable to individual physiologic adjustments due to prior cold exposure patterns of divers. This suggests that variations in metabolic adjustments and habituation to the cold were likely. More work is needed to fully understand inter-individual metabolic variability to prolonged cold-water submersion.