bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Unbound Proline-Rich Signaling Peptide Frequently Samples Cis Conformations in Gaussian Accelerated Molecular Dynamics Simulations
Authors: Alcantara Juan , Stix Robyn , Huang Katherine , Connor Acadia , East Ray , Jaramillo-Martinez Valeria , Stollar Elliott J. , Ball K. Aurelia 
Published: November 2021

Disordered proline-rich motifs are common across the proteomes of many species and are often involved in protein-protein interactions. Proline is a unique amino acid due to the covalent bond between the backbone nitrogen and the proline side chain. The resulting five-membered ring allows proline to sample the cis state about its peptide bond, which other residues cannot do as readily. Because proline-rich disordered sequences exist as ensembles that likely include structures with the proline peptide bond in cis, a robust methodology to accurately account for these conformations in the overall ensemble is crucial. Observing the cis conformations of proline in a disordered sequence is challenging both experimentally and computationally. Nitrogen-hydrogen NMR spectroscopy cannot directly observe proline residues, which lack an amide bond, and computational methods struggle to overcome the large kinetic barrier between the cis and trans states, since isomerization usually occurs on the order of seconds. In the current work, Gaussian accelerated molecular dynamics was used to overcome this free energy barrier and simulate proline isomerization in a tetrapeptide (KPTP) and in the 12-residue proline-rich SH3 binding peptide, ArkA. We found that Gaussian accelerated molecular dynamics, when combined with a lowered peptide bond dihedral angle potential energy barrier (15 kcal/mol), allowed sufficient sampling of the proline cis and trans states on a microsecond timescale. All ArkA prolines spend a significant fraction of time in cis, leading to a more compact ensemble with less polyproline II helix structure than an ArkA ensemble with all peptide bonds in trans. The ensemble containing cis prolines also matches more closely to in vitro circular dichroism data than the all-trans ensemble. The ability of the ArkA prolines to isomerize likely affects the peptide’s ability to bind its partner SH3 domain, and should be studied further. This is the first molecular dynamics simulation study of proline isomerization in a biologically relevant proline-rich sequence that we know of, and a similar protocol could be applied to study multi-proline isomerization in other proline-containing proteins to improve conformational diversity and agreement with in vitro data.
Identification of Clinical and Tumor Microenvironment Characteristics of Hypoxia-Related Risk Signature in Lung Adenocarcinoma
Authors: Dai Zili , Liu Taisheng , Liu Guihong , Deng Zhen , Yu Peng , Wang Baiyao , Cen Bohong , Guo Liyi , Zhang Jian 
Published: November 2021

Background: Lung cancer is the leading cause of cancer-related death globally. Hypoxia can suppress the activation of the tumor microenvironment (TME), which contributes to distant metastasis. However, the role of hypoxia-mediated TME in predicting the diagnosis and prognosis of lung adenocarcinoma (LUAD) patients remains unclear.Methods: Both RNA and clinical data from the LUAD cohort were downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Both univariate and multivariate Cox regression analyses were used to further screen prognosis-related hypoxia gene clusters. Time-dependent receiver operation characteristic (ROC) curves were established to evaluate the predictive sensitivity and specificity of the hypoxia-related risk signature. The characterization of gene set enrichment analysis (GSEA) and TME immune cell infiltration were further explored to identify hypoxia-related immune infiltration.Results: Eight hypoxia-related genes (LDHA, DCN, PGK1, PFKP, FBP1, LOX, ENO3, and CXCR4) were identified and established to construct a hypoxia-related risk signature. The high-risk group showed a poor overall survival compared to that of the low-risk group in the TCGA and GSE68465 cohorts (p &lt; 0.0001). The AUCs for 1-, 3-, and 5-year overall survival were 0.736 vs. 0.741, 0.656 vs. 0.737, and 0.628 vs. 0.649, respectively. The high-risk group was associated with immunosuppression in the TME.Conclusion: The hypoxia-related risk signature may represent an independent biomarker that can differentiate the characteristics of TME immune cell infiltration and predict the prognosis of LUAD.
Focal Seizures and Posterior Reversible Encephalopathy Syndrome as Presenting Signs of IgA Vasculitis/Henoch-Schoenlein Purpura—An Educative Case and Systematic Review of the Literature
Authors: Funken Dominik , Götz Friedrich , Bültmann Eva , Hennies Imke , Gburek-Augustat Janina , Hempel Julya , Dressler Frank , Baumann Ulrich , Klemann Christian 
Published: November 2021

Background:IgA vasculitis/Henoch-Schoenlein purpura (IgAV/HSP) is a systemic small vessel vasculitis of unknown pathogenesis predominantly affecting children. While skin, GI tract, joints, and kidneys are frequently affected and considered, central nervous system (CNS) involvement of this disease is underestimated.Methods:We provide a case report and systematically review the literature on IgAV, collecting data on the spectrum of neurological manifestations.Results:We report on a 7-year-old girl with IgAV who presented with diplopia and afebrile focal seizures, which preceded the onset of purpura. Cranial magnetic resonance imaging was consistent with posterior reversible encephalopathy syndrome (PRES), showing typical focal bilateral parietal swelling and cortical and subcortical high signal intensities on T2-fluid attenuated inversion recovery (FLAIR) images predominantly without diffusion restriction. Cerebrospinal fluid analysis and blood tests excluded systemic inflammation or vasculitis. Interestingly, hypertension was not a hallmark of the developing disease in the initial phase of PRES manifestation. Renal disease and other secondary causes for PRES were also excluded. Supportive- and steroid treatment resulted in restitutionad integrum. Reviewing the literature, we identified 28 other cases of IgAV with CNS involvement. Severe CNS involvement includes seizures, cerebral edema, or hemorrhage, as well as PRES. Thirteen patients fulfilled all diagnostic criteria of PRES. The mean age was 11.2 years (median 8.0, range 5-42 years), with no reported bias toward gender or ethnic background. Treatment regimens varied from watchful waiting to oral and intravenously steroids up to plasmapheresis. Three cases showed permanent CNS impairment.Conclusion:Collectively, our data demonstrate that (I) severe CNS involvement such as PRES is an underappreciated feature of IgAV, (II) CNS symptoms may precede other features of IgAV, (III) PRES can occur in IgAV, and differentiation from CNS vasculitis is challenging, (IV) pathogenesis of PRES in the context of IgAV remains elusive, which hampers treatment decisions. We, therefore, conclude that clinical awareness and the collection of structured data are necessary to elucidate the pathophysiological connection of IgAV and PRES.
A Pilot Study Examining Body Composition Classification Differences Between Body Mass Index and Bioelectrical Impedance Analysis in Children With High Levels of Physical Activity
Authors: Farbo David J. , Rhea Deborah J. 
Published: November 2021

Background: Body mass index (BMI) is frequently labeled as “flawed” in assessing obesity since it cannot differentiate between muscle and fat leading to misclassifications of healthy individuals. Bioelectrical impedance analysis (BIA) may be a more accurate indicator of obesity since it can distinguish the difference between muscle and fat in children. This pilot study investigated discrepancies between BMI and BIA body composition classifications in children with high levels of physical activity.Methods: Participants were selected from three elementary schools (N = 380, K = 76, 1st = 64, 2nd = 62, 3rd = 61, 4th = 83, and 5th = 34) receiving 60 min of outdoor, unstructured play daily. BIA scales were used to collect each child's body fat percentage and BMI score, then those numbers were categorized by BIA and BMI normative values as either underweight, healthy, overweight, or obese.Results: Overall, 26% of the students were classified differently when using the normative classifications for BMI and BIA, with the largest discrepancy found in the overweight category at 38%. Similar inconsistencies were found when students were divided as younger (42%) vs older students (36%), and males (40%) vs. females (35%).Conclusions: This pilot study demonstrated that there is a significant difference in how BMI and BIA discriminate between the different body composition categories. BIA consistently shows to be a more accurate tool in assessing obesity rates in children since it directly measures body fat.
Neonatal Morbidity and Mortality in Advanced Aged Mothers—Maternal Age Is Not an Independent Risk Factor for Infants Born Very Preterm
Authors: Nourkami-Tutdibi Nasenien , Tutdibi Erol , Faas Theresa , Wagenpfeil Gudrun , Draper Elizabeth S. , Johnson Samantha , Cuttini Marina , Rafei Rym El , Seppänen Anna-Veera , Mazela Jan , Maier Rolf Felix , Nuytten Alexandra , Barros Henrique , Rodrigues Carina , Zeitlin Jennifer , Zemlin Michael 
Published: November 2021

Background: As childbearing is postponed in developed countries, maternal age (MA) has increased over decades with an increasing number of pregnancies between age 35–39 and beyond. The aim of the study was to determine the influence of advanced (AMA) and very advanced maternal age (vAMA) on morbidity and mortality of very preterm (VPT) infants.Methods: This was a population-based cohort study including infants from the “Effective Perinatal Intensive Care in Europe” (EPICE) cohort. The EPICE database contains data of 10329 VPT infants of 8,928 mothers, including stillbirths and terminations of pregnancy. Births occurred in 19 regions in 11 European countries. The study included 7,607 live born infants without severe congenital anomalies. The principal exposure variable was MA at delivery. Infants were divided into three groups [reference 18–34 years, AMA 35–39 years and very(v) AMA ≥40 years]. Infant mortality was defined as in-hospital death before discharge home or into long-term pediatric care. The secondary outcome included a composite of mortality and/or any one of the following major neonatal morbidities: (1) moderate-to-severe bronchopulmonary dysplasia; (2) severe brain injury defined as intraventricular hemorrhage and/or cystic periventricular leukomalacia; (3) severe retinopathy of prematurity; and (4) severe necrotizing enterocolitis.Results: There was no significant difference between MA groups regarding the use of surfactant therapy, postnatal corticosteroids, rate of neonatal sepsis or PDA that needed pharmacological or surgical intervention. Infants of AMA/vAMA mothers required significantly less mechanical ventilation during NICU stay than infants born to non-AMA mothers, but there was no significant difference in length of mechanical ventilation and after stratification by gestational age group. Adverse neonatal outcomes in VPT infants born to AMA/vAMA mothers did not differ from infants born to mothers below the age of 35. Maternal age showed no influence on mortality in live-born VPT infants.Conclusion: Although AMA/vAMA mothers encountered greater pregnancy risk, the mortality and morbidity of VPT infants was independent of maternal age.
Oral Mycobiome Differences in Various Spatial Niches With and Without Severe Early Childhood Caries
Authors: Cui Yuqi , Wang Yinuo , Zhang Yuwen , Pang Liangyue , Zhou Yan , Lin Huancai , Tao Ye 
Published: November 2021

Purpose: Severe early childhood caries (S-ECC) is a microbe-mediated disease with tooth hard tissue destruction. However, the role of the fungal community in various ecological niches of deciduous dental caries has not been fully elucidated. This study aimed to analyze the differences of mycobiome in diverse spatial niches with and without S-ECC.Method: A total of 48 samples were obtained from 8 S-ECC children (SE group) and 8 caries-free children (CF group) aged 4–5 years. Unstimulated saliva (S), healthy supragingival plaque (FMIX), mixed plaque from decayed teeth (SMIX) and carious lesion (DMIX) samples were collected. The ITS2 region of the fungi was amplified and sequenced using the Ion S5™XL platform.Results: A total of 281 species were identified. Candida albicans showed relatively higher abundance in S-ECC children, while Alternaria alternata and Bipolaris sorokiniana were more enriched in CF group. In this study, the relative abundance of C. albicans in CF.FMIX (0.4%), SE.FMIX (12.5%), SE.SMIX (24.0%), and SE.DMIX (37.2%) increased successively. Significant differences of fungal species richness and diversity were observed between SE.FMIX-SE.SMIX, SE.FMIX-SE.DMIX (P &lt; 0.05).Conclusions: The diversity of fungal communities in S-ECC children showed significant differences in various spatial niches of primary teeth. The richness of C. albicans was closely related to the caries states and depth, suggesting that it may play a crucial role in caries pathogenicity.
9-PAHSA Improves Cardiovascular Complications by Promoting Autophagic Flux and Reducing Myocardial Hypertrophy in Db/Db Mice
Authors: Wang Yan-Mei , Mi Shou-Ling , Jin Hong , Guo Qi-Lin , Yu Zhong-Yu , Wang Jian-Tao , Zhang Xiao-Ming , Zhang Qian , Wang Na-Na , Huang Yan-Yan , Zhou Hou-Guang , Guo Jing-Chun 
Published: November 2021

Atherosclerotic cardiovascular disease is a common and severe complication of diabetes. There is a large need to identify the effective and safety strategies on diabetic cardiovascular disease (DCVD). 9-PAHSA is a novel endogenous fatty acid, and has been reported to reduce blood glucose levels and attenuate inflammation. We aim to evaluate the effects of 9-PAHSA on DCVD and investigate the possible mechanisms underlying it. Firstly, serum 9-PAHSA levels in human were detected by HPLC-MS/MS analysis. Then 9-PAHSA was synthesized and purified. The synthesized 9-PAHSA was gavaged to db/db mice with 50 mg/kg for 4 weeks. The carotid arterial plaque and cardiac structure was assessed by ultrasound. Cardiac autophagy was tested by western blot analysis, electron microscope and iTRAQ. The results showed that 9-PAHSA, in patients with type 2 diabetes mellitus (T2DM), was significantly lower than that in non-diabetic subjects. Administration of 9-PAHSA for 2 weeks reduced blood glucose levels. Ultrasound observed that continue administration of 9-PAHSA for 4 weeks ameliorated carotid vascular calcification, and attenuated myocardial hypertrophy and dysfunction in db/db mice. Electron microscopy showed continue 9-PAHSA treatment significantly increased autolysosomes, while dramatically decreased greases in the myocardial cells of the db/db mice. Moreover, iTRAQ analysis exhibited that continue 9-PAHSA treatment upregulated BAG3 and HSPB8. Furthermore, western blot analysis confirmed that 9-PAHSA down-regulated Akt/mTOR and activated PI3KIII/BECN1 complex in diabetic myocardium. Thus, 9-PAHSA benefits DCVD in diabetic mice by ameliorating carotid vascular calcification, promoting autophagic flux and reducing myocardial hypertrophy.
The Clinical Value of Chemotherapy Combined With Capecitabine in Triple-Negative Breast Cancer—A Meta-Analysis
Authors: Zhang Zilin , Ma Kai , Li Jing , Guan Yeneng , Yang Chaobo , Yan Aqin , Zhu Hongda 
Published: November 2021

Purpose: Triple-negative breast cancer (TNBC) is the most dangerous subtype of breast cancer with high rates of metastasis and recurrence. The efficacy of capecitabine in chemotherapy for TNBC is still controversial. This study evaluated the efficacy and safety of capecitabine combining with standard, adjuvant or neoadjuvant chemotherapy for TNBC.Methods: We systematically searched clinical studies through PubMed, Cochrane library, Embase, Wanfang Database, China Academic Journals (CNKI), and American Society of Clinical Oncology’s (ASCO) annual conference report. Studies were assessed for design and quality by the Cochrane risk of bias tool. A meta-analysis was performed using Review Manager to quantify the effect of capecitabine combined with standard, adjuvant or neoadjuvant chemotherapy on the disease-free survival (DFS) rate and overall survival (OS) rate of TNBC patients. Furthermore, safety analysis was performed to evaluate the adverse events.Results: Twelve randomized controlled clinical trials involving totally 4854 TNBC patients were included, of which 2,214 patients received chemotherapy as control group, and 2,278 patients received capecitabine combining with chemotherapy. The results indicated that capecitabine could significantly improve the DFS [hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.71–0.90, P = 0.0003] and OS (HR 0.83, 95% CI 0.74–0.93, P = 0.001). In subgroup analysis, the combination of capecitabine and cyclophosphamide exhibited a significant benefit in all outcomes (DFS HR 0.75, 95% CI 0.63–0.90, P = 0.002; OS HR 0.65, 95% CI 0.52–0.80, p &lt; 0.0001). Additionally, defferent dose of capecitabine subgroup showed same significant effect on the results. Safety analysis showed that the addition of capecitabine was associated with a much higher risk of hand-foot syndrome, diarrhea and mucositis or stomatitis.Conclusion: The results showed that adjuvant capecitabine could bring significant benefits on DFS and OS to unselected TNBC patients, the combination of capecitabine and cyclophosphamide could improve the survival rate of patients, although the addition of capecitabine could bring significant side effects such as hand foot syndrome (HFS) and diarrhea.
Avoiding Crowded Places During COVID-19: Common Sense or a Complex Strategic Decision?
Authors: Stroom Martijn , Eichholtz Piet , Kok Nils 
Published: November 2021

Introduction:Following a period of strict lockdowns during the COVID-19 pandemic, most countries introduced policies in which citizens were expected to avoid crowded places using common sense, as advised by the WHO. We argue that the ambiguity in the recommendation to “avoid crowded places” implicitly forces individuals to make a complex strategic decision.Methods:Using a Dutch representative sample of 1,048 participants [42% male, mean age=43.78years (SD=12.53), we examine the effect of context on the decision to visit a hypothetical recreational hotspot under the policy recommendation to “avoid crowded places.” We randomize four levels of context on the crowdedness “on the streets” (no context, low, medium, and high context). Subsequently, participants are asked to estimate the percentage of others going out in the same situation. Finally, we assess the impact of a selection of personal characteristics on the likelihood of visiting a crowded place.Results:Respondents are proportionally more likely to go in a low context and high context, compared to no context (diff=0.121,p&lt;0.000, and diff=0.034,p&lt;0.05, respectively) and middle context (diff=0.125,p&lt;0.000, and diff=0.037,p&lt;0.05, respectively). Low context information also decreases the expectation of others going out (−2.63%,z=4.68,p&lt;0.000). High context information increases the expected percentage of others going out (significant only for medium to high context; 2.94%,z=7.34,p&lt;0.001). Furthermore, we show that education, age, and health and risk attitude are all predictive of the likelihood to visit a crowded place, notwithstanding the context.Discussion:Although there is a strong inclination to avoid crowded places during the COVID-19 pandemic (81%), we find two context-driven exceptions: when people expect to avoid crowded spots (in the “low” context, i.e., strategical decision-making) and when people expect others to go (social influence). The freedom provided by ambiguous public policy is implicitly asking more from the population than it initially seems. “Use your common sense” is often the accompanied advice, but our results show that more and better information concerning the context is essential to enable us to make an optimal decision for ourselves, and for society.
Effects of Electroacupuncture Combined With Psychological Intervention on Depressive Status and Contingent Negative Variation in Patients With Internet Addiction Disorder: A Randomized Controlled Trial
Authors: Peng Wei , Wang Yang , Hao Qinghong , Wang Jun , Chen Yalin , Qiu Mimi , Tu Yang , Li Hui , Zhu Tianmin 
Published: November 2021

Background: Depressive symptoms often accompany people with Internet addiction syndrome (IAD). Acupuncture has been found to have significant advantages in improving the severity and depressive symptoms of IAD. Contingent negative variation (CNV) is a common method to explore the mechanism of neurophysiology.Objective: The purpose of this study was to observe the efficacy of electroacupuncture (EA), psychological intervention (PI), and comprehensive intervention (CI) in the treatment of depression in Internet addiction disorder (IAD), and to observe the changes of contingent negative variation (CNV) in each group.Methods: One hundred and twenty subjects diagnosed with IAD were randomly assigned to the EA group, the PI group, or the CI group. They received EA, PI, or a combination of EA and PI for 40 days. The Internet Addiction Test (IAT), the Zung Self-rating Depression Scale (SDS), and the Hamilton Depression Scale (HAMD) were evaluated for all subjects at baseline, 20th, and 40th days of treatment, while CNV data were collected at baseline and 40th days of treatment.Results: Three treatments effectively reduced IAT, SDS, and HAMD scores, and the intergroup comparison showed that CI was superior to EA, while EA was superior to PI. CNV results indicated that the CNV amplitude increased in all three groups of IAD patients after treatment. The CNV latency of point A and A-S2' wave area of the EA group and the CI group did not change significantly after treatment. Only the A-S2' wave area of the PI group increased significantly compared with the baseline period. In addition, IAD's IAT score was positively correlated with SDS and HAMD score at baseline but negatively correlated with CNV latency. After treatment, only the change of HAMD score in the CI group was negatively correlated with amplitude.Conclusion: Our results demonstrate the efficacy of acupuncture and psychological intervention in the treatment of IAD from an electrophysiological perspective. Simultaneously, the increase in CNV amplitude might be the underlying neurophysiological mechanism by which CI improves depression and cognitive function in IAD patients.Clinical Trial Registration:ClinicalTrials.gov, identifier NCT02362698.