bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Genetic Signature Associated With Aging in Pulmonary Fibrosis
Authors: Lu Yanjiao , Chen Jinkun , Wang Shanshan , Tian Zhen , Fan Yan , Wang Meijia , Zhao Jianping , Tang Kun , Xie Jungang 
Published: October 2021

Background: Aging is a strong risk factor and an independent prognostic factor in idiopathic pulmonary fibrosis (IPF). In this study, we aimed to conduct a comprehensive analysis based on gene expression profiles for the role of aging in pulmonary fibrosis.Method: Four datasets (GSE21411, GSE24206, GSE47460, and GSE101286) for patients with clinical IPF and one dataset for bleomycin (BLM)-induced pulmonary fibrosis (BIPF) mouse model (GSE123293) were obtained from Gene Expression Omnibus (GEO). According to different age ranges, both patients with IPF and BIPF mice were divided into young and aged groups. The differently expressed genes (DEGs) were systemically analyzed using Gene Ontology (GO) functional, Kyoto Encyclopedia of Genes and Genomes (KEGG), and hub genes analysis. Finally, we verified the role of age and core genes associated with age in vivo.Results:Via the expression profile comparisons of aged and young patients with IPF, we identified 108 aging-associated DEGs, with 21 upregulated and 87 downregulated. The DEGs were associated with “response to glucocorticoid,” “response to corticosteroid,” and “rhythmic process” in GO biological process (BP). For KEGG analysis, the top three significantly enriched KEGG pathways of the DEGs included “IL-17 signaling pathway,” “Mineral absorption,” and “HIF-1-signaling pathway.” Through the comparisons of aged and young BIPF mice, a total number of 778 aging-associated DEGs were identified, with 453 genes increased and 325 genes decreased. For GO and KEGG analysis, the DEGs were enriched in extracellular matrix (ECM) and collagen metabolism. The common DEGs of patients with IPF and BIPF mice were enriched in the BP category, including “induction of bacterial agglutination,” “hyaluronan biosynthetic process,” and “positive regulation of heterotypic cell-cell adhesion.” We confirmed that aged BIPF mice developed more serious pulmonary fibrosis. Finally, the four aging-associated core genes (Slc2a3, Fga, Hp, and Thbs1) were verified in vivo.Conclusion: This study provides new insights into the impact of aging on pulmonary fibrosis. We also identified four aging-associated core genes (Slc2a3, Fga, Hp, and Thbs1) related to the development of pulmonary fibrosis.
Epidemiology and Regional Predictors of COVID-19 Clusters: A Bayesian Spatial Analysis Through a Nationwide Contact Tracing Data
Authors: Hong Kwan , Yum Sujin , Kim Jeehyun , Yoo Daesung , Chun Byung Chul 
Published: October 2021

Purpose: Revealing the clustering risks of COVID-19 and prediction is essential for effective quarantine policies, since clusters can lead to rapid transmission and high mortality in a short period. This study aimed to present which regional and social characteristics make COVID-19 cluster with high risk.Methods: By analyzing the data of all confirmed cases (14,423) in Korea between January 10 and August 3, 2020, provided by the Korea Disease Control and Prevention Agency, we manually linked each case and discovered clusters. After classifying the cases into clusters as nine types, we compared the duration and size of clusters by types to reveal high-risk cluster types. Also, we estimated odds for the risk factors for COVID-19 clustering by a spatial autoregressive model using the Bayesian approach.Results: Regarding the classified clusters (n = 539), the mean size was 19.21, and the mean duration was 9.24 days. The number of clusters was high in medical facilities, workplaces, and nursing homes. However, multilevel marketing, religious facilities, and restaurants/business-related clusters tended to be larger and longer when an outbreak occurred. According to the spatial analysis in COVID-19 clusters of more than 20 cases, the global Moran's I statistics value was 0.14 (p &lt; 0.01). After adjusting for population size, the risks of COVID-19 clusters were related to male gender (OR = 1.29) and low influenza vaccination rate (OR = 0.87). After the spatial modeling, the predicted probability of forming clusters was visualized and compared with the actual incidence and local Moran's I statistics 2 months after the study period.Conclusions: COVID-19 makes different sizes of clusters in various contact settings; thus, precise epidemic control measures are needed. Also, when detecting and screening for COVID-19 clusters, regional risks such as vaccination rate should be considered for predicting risk to control the pandemic cost-effectively.
Dining in Blue Light Impairs the Appetite of Some Leaf Epiphytes
Authors: Alsanius Beatrix W. , Vaas Lea , Gharaie Samareh , Karlsson Maria E. , Rosberg Anna Karin , Wohanka Walter , Khalil Sammar , Windstam Sofia 
Published: October 2021

Background:The phyllosphere is subjected to fluctuating abiotic conditions. This study examined the phenotypic plasticity (PP) of four selected non-phototrophic phyllosphere bacteria [control strain:Pseudomonassp. DR 5-09;Pseudomonas agarici,Bacillus thuringiensisserovarisraeliensis(Bti), andStreptomyces griseoviridis(SG)] regarding their respiration patterns and surfactant activity as affected by light spectrum and nutrient supply.Methods:The PP of the strains was examined under four light regimes [darkness (control); monochromatic light-emitting diodes (LED) at 460 nm (blue) and 660 nm (red); continuously polychromatic white LEDs], in the presence of 379 substrates and conditions.Results:Light treatment affected the studied bacterial strains regarding substrate utilization (Pseudomonasstrains &gt; SG &gt; Bti). Blue LEDs provoked the most pronounced impact on the phenotypic reaction norms of thePseudomonasstrains and Bti. The two Gram-positive strains Bti and SG, respectively, revealed inconsistent biosurfactant formation in all cases. Biosurfactant formation by bothPseudomonasstrains was supported by most substrates incubated in darkness, and blue LED exposure altered the surface activity profoundly. Blue and white LEDs enhanced biofilm formation in PA in highly utilized C-sources. Putative blue light receptor proteins were found in bothPseudomonasstrains, showing 91% similarity with the sequence from NCBI accession numberWP_064119393.Conclusion:Light quality–nutrient interactions affect biosurfactant activity and biofilm formation of some non-phototrophic phyllosphere bacteria and are, thus, crucial for dynamics of the phyllosphere microbiome.
Sleep Quality Mediates the Association Between Cerebral Small Vessel Disease Burden and Frailty: A Community-Based Study
Authors: Zhao Jing , Qu Wensheng , Zhou Xirui , Guo Yinping , Zhang Yi , Wu Lingshan , Yu Zhiyuan , Huang Hao , Luo Xiang 
Published: October 2021

Background: Physical frailty is a common problem among older adults which usually leads to adverse health outcomes. The imaging markers of cerebral small vessel disease (CSVD) are associated with frailty, but the underlying mechanisms remain unclear. The present study aimed to investigate the mediating role of sleep quality in the relationship between CSVD burden and frailty.Methods: We performed a cross-sectional study and enrolled community residents. Frailty and sleep quality were measured using the Fried frailty phenotype and the Pittsburgh Sleep Quality Index (PSQI), respectively. A multivariate linear regression analysis and a Bootstrap analysis were performed to examine the association among the key variables and the mediating role of sleep quality.Results: Of the 726 participants (mean age: 65.5 ± 6.5 years, 59.8% female), the numbers (percentages) of the frail, prefrail, and robust residents were 49 (6.7%), 310 (42.7%), and 367 (50.6%), respectively. After adjusting for covariates, the CSVD burden and PSQI score were significantly associated with the frailty score. In addition, sleep quality played a partial mediating role in the association between CSVD burden and physical frailty. The mediating effect was 21.9%.Conclusion: The present study suggests that sleep quality is a mediator of this association between CSVD and frailty in community-dwelling older adults. Improving sleep quality might be helpful to mitigate the risk of frailty in CSVD patients.
Distribution of Diagnoses and Clinical and Imaging Characteristics in 1,322 Consecutive Suspected Stroke Patients
Authors: Sporns Peter B. , Brehm Alex , Hilgers Caroline , Ntoulias Nikolaos , Tsogkas Ioannis , Psychogios Marios 
Published: October 2021

Background: Endovascular thrombectomy (EVT) has become the standard of care for large-vessel occlusion strokes, but several barriers for implementing an optimal organization of stroke management remain. Major issues include the lack of reliable data on the percentage of stroke patients potentially eligible for EVT especially in times of expanding indications for EVT. Our aim was therefore to study the frequencies of possible EVT-eligible patients such as patients with medium-vessel occlusions, patients with low Alberta Stroke Program Early Computed Tomography Scores (ASPECTS), patients presenting in an extended time window after onset of symptoms, and patients with mild symptoms at presentation (National Institutes of Health Stroke Scale, NIHSS ≤ 5). We also give detailed imaging and clinical information about the patients presenting with intracranial hemorrhage and other ischemic stroke mimics stratified by symptoms at presentation.Methods: Cohort study of all consecutive patients with suspected acute stroke presenting to a tertiary care center in Germany between September 1, 2016, and August 31, 2017. Baseline and follow-up clinical and imaging characteristics were collected from patients' medical charts.Results: Of 1,322 patients with a suspected acute stroke, 592 (44.8%) had ischemic strokes, 221 (16.7%) had hemorrhagic strokes, 190 (10.9%) had transient ischemic attacks (TIAs), and 319 (24.1%) were classified as stroke mimics. Stroke severity was mild (NIHSS ≤ 5) in 866 (65.5%) patients; 15.7% of the patients with an occlusion of the anterior circulation had an ASPECTS ≤ 5, 17.4% of the patients with an ischemic stroke had distal vessel occlusions, and 49% of the patients presented later than 6 h after onset of symptoms.Conclusion: Our results help to plan resources in thrombectomy-capable centers in times of expanding indications for EVT where resources will have to be adjusted to patients with low-NIHSS, low-ASPECTS, and distal occlusions, and patients presenting in the extended time window, which may altogether account for an additional 20% of all ischemic stroke patients.
Patient-Reported Outcomes-Guided Adaptive Radiation Therapy for Head and Neck Cancer
Authors: Weppler Sarah , Quon Harvey , Schinkel Colleen , Yarschenko Adam , Barbera Lisa , Harjai Nabhya , Smith Wendy 
Published: October 2021

PurposeTo identify which patient-reported outcomes (PROs) may be most improved through adaptive radiation therapy (ART) with the goal of reducing toxicity incidence among head and neck cancer patients.MethodsOne hundred fifty-five head and neck cancer patients receiving radical VMAT (chemo)radiotherapy (66-70 Gy in 30-35 fractions) completed the MD Anderson Symptom Inventory, MD Anderson Dysphagia Inventory (MDADI), and Xerostomia Questionnaire while attending routine follow-up clinics between June-October 2019. Hierarchical clustering characterized symptom endorsement. Conventional statistical approaches indicated associations between dose and commonly reported symptoms. These associations, and the potential benefit of interfractional dose corrections, were further explored via logistic regression.ResultsRadiotherapy-related symptoms were commonly reported (dry mouth, difficulty swallowing/chewing). Clustering identified three patient subgroups reporting: none/mild symptoms for most items (60.6% of patients); moderate/severe symptoms affecting some aspects of general well-being (32.9%); and moderate/severe symptom reporting for most items (6.5%). Clusters of PRO items broadly consisted of acute toxicities, general well-being, and head and neck-specific symptoms (xerostomia, dysphagia). Dose-PRO relationships were strongest between delivered pharyngeal constrictor Dmean and patient-reported dysphagia, with MDADI composite scores (mean ± SD) of 25.7 ± 18.9 for patients with Dmean &lt;50 Gy vs. 32.4 ± 17.1 with Dmean ≥50 Gy. Based on logistic regression models, during-treatment dose corrections back to planned values may confer ≥5% decrease in the absolute risk of self-reported physical dysphagia symptoms ≥1 year post-treatment in 1.2% of patients, with a ≥5% decrease in relative risk in 23.3% of patients.ConclusionsPatient-reported dysphagia symptoms are strongly associated with delivered dose to the pharyngeal constrictor. Dysphagia-focused ART may provide the greatest toxicity benefit to head and neck cancer patients, and represent a potential new direction for ART, given that the existing ART literature has focused almost exclusively on xerostomia reduction.
PROTEA, A Southern African Multicenter Congenital Heart Disease Registry and Biorepository: Rationale, Design, and Initial Results
Authors: Aldersley Thomas , Lawrenson John , Human Paul , Shaboodien Gasnat , Cupido Blanche , Comitis George , De Decker Rik , Fourie Barend , Swanson Lenise , Joachim Alexia , Magadla Phaphama , Ngoepe Malebogo , Swanson Liam , Revell Alistair , Ramesar Raj , Brooks Andre , Saacks Nicole , De Koning Bianca , Sliwa Karen , Anthony John , Osman Ayesha , Keavney Bernard , Zühlke Liesl 
Published: October 2021

Objectives: The PartneRships in cOngeniTal hEart disease (PROTEA) project aims to establish a densely phenotyped and genotyped Congenital Heart Disease (CHD) cohort for southern Africa. This will facilitate research into the epidemiology and genetic determinants of CHD in the region. This paper introduces the PROTEA project, characterizes its initial cohort, from the Western Cape Province of South Africa, and compares the proportion or “cohort-prevalences” of CHD-subtypes with international findings.Methods: PROTEA is a prospective multicenter CHD registry and biorepository. The initial cohort was recruited from seven hospitals in the Western Cape Province of South Africa from 1 April 2017 to 31 March 2019. All patients with structural CHD were eligible for inclusion. Descriptive data for the preliminary cohort are presented. In addition, cohort-prevalences (i.e., the proportion of patients within the cohort with a specific CHD-subtype) of 26 CHD-subtypes in PROTEA's pediatric cohort were compared with the cohort-prevalences of CHD-subtypes in two global birth-prevalence studies.Results: The study enrolled 1,473 participants over 2 years, median age was 1.9 (IQR 0.4–7.1) years. Predominant subtypes included ventricular septal defect (VSD) (339, 20%), atrial septal defect (ASD) (174, 11%), patent ductus arteriosus (185, 11%), atrioventricular septal defect (AVSD) (124, 7%), and tetralogy of Fallot (121, 7%). VSDs were 1.8 (95% CI, 1.6–2.0) times and ASDs 1.4 (95% CI, 1.2–1.6) times more common in global prevalence estimates than in PROTEA's pediatric cohort. AVSDs were 2.1 (95% CI, 1.7–2.5) times more common in PROTEA and pulmonary stenosis and double outlet right ventricle were also significantly more common compared to global estimates. Median maternal age at delivery was 28 (IQR 23–34) years. Eighty-two percent (347/425) of mothers used no pre-conception supplementation and 42% (105/250) used no first trimester supplements.Conclusions: The cohort-prevalence of certain mild CHD subtypes is lower than for international estimates and the cohort-prevalence of certain severe subtypes is higher. PROTEA is not a prevalence study, and these inconsistencies are unlikely the result of true differences in prevalence. However, these findings may indicate under-diagnosis of mild to moderate CHD and differences in CHD management and outcomes. This reemphasizes the need for robust CHD epidemiological research in the region.
Herbal Medicine Compared to Placebo for Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis
Authors: Kwon Chan-Young , Lee Boram , Lee Beom-Joon , Kim Kwan-Il , Jung Hee-Jae 
Published: October 2021

Chronic obstructive pulmonary disease (COPD) is a respiratory disease characterized by irreversible airflow limitation. Many COPD patients use complementary and alternative modalities, including herbal medicines (HMs). This systematic review investigated the effectiveness and safety of HM in managing COPD symptoms compared to placebo. Nine electronic databases were searched to identify relevant randomized controlled trials (RCTs) up to February 12, 2021. The Cochrane risk of bias tool was used to assess the methodological qualities of the included studies. Primary outcomes were lung function parameters and exercise capacity. A meta-analysis was conducted to determine the effect size for homogeneous outcomes. Fourteen studies were included. There was low to very low quality evidence that HM significantly improved forced expiratory volume in 1  s (FEV1) (L), FEV1 (%) and 6-minute walk distance, as well as moderate quality evidence that HM significantly improved forced vital capacity (FVC) (L) compared to placebo. However, according to low quality evidence, there was no significant difference in FEV1/FVC (%) or vital capacity (L) between the groups. Low to moderate evidence suggests that HM has the potential to help improve some respiratory functions, COPD symptoms, and some aspects of quality of life in COPD patients compared to placebo. However, these findings are challenged by the poor methodological quality of the included studies, the heterogeneity of HMs used, and potential publication bias. Therefore, the findings could be significantly influenced by further larger, more rigorous RCTs on this topic. Moreover, it may also be recommended to develop standardized HMs focused on some individual herbs that are frequently used or expected to play an important role in patients with COPD, and to elucidate the underlying mechanisms.
Effect of CYP3A4 Inhibitors and Inducers on Pharmacokinetics and Pharmacodynamics of Saxagliptin and Active Metabolite M2 in Humans Using Physiological-Based Pharmacokinetic Combined DPP-4 Occupancy
Authors: Li Gang , Yi Bowen , Liu Jingtong , Jiang Xiaoquan , Pan Fulu , Yang Wenning , Liu Haibo , Liu Yang , Wang Guopeng 
Published: October 2021

We aimed to develop a physiological-based pharmacokinetic and dipepidyl peptidase 4 (DPP-4) occupancy model (PBPK-DO) characterized by two simultaneous simulations to predict pharmacokinetic (PK) and pharmacodynamic changes of saxagliptin and metabolite M2 in humans when coadministered with CYP3A4 inhibitors or inducers. Ketoconazole, delavirdine, and rifampicin were selected as a CYP3A4 competitive inhibitor, a time-dependent inhibitor, and an inducer, respectively. Here, we have successfully simulated PK profiles and DPP-4 occupancy profiles of saxagliptin in humans using the PBPK-DO model. Additionally, under the circumstance of actually measured values, predicted results were good and in line with observations, and all fold errors were below 2. The prediction results demonstrated that the oral dose of saxagliptin should be reduced to 2.5 mg when coadministrated with ketoconazole. The predictions also showed that although PK profiles of saxagliptin showed significant changes with delavirdine (AUC 1.5-fold increase) or rifampicin (AUC: a decrease to 0.19-fold) compared to those without inhibitors or inducers, occupancies of DPP-4 by saxagliptin were nearly unchanged, that is, the administration dose of saxagliptin need not adjust when there is coadministration with delavirdine or rifampicin.
Lactate Dehydrogenase A or B Knockdown Reduces Lactate Production and Inhibits Breast Cancer Cell Motility in vitro
Authors: Khajah Maitham A. , Khushaish Sarah , Luqmani Yunus A. 
Published: October 2021

Background: Lactate dehydrogenase (LDH) plays an important role in cancer pathogenesis and enhanced expression/activity of this enzyme has been correlated with poor prognosis. In this study we determined the expression profile of LDH-A and B in normal as well as in endocrine-resistant and -responsive breast cancer cells and the effect of their knockdown on LDH activity, lactate production, proliferation and cell motility.Methods: Knockdown experiments were performed using siRNA and shRNA. The expression profile of LDH and signaling molecules was determined using PCR and western blotting. Intracellular LDH activity and extracellular lactate levels were measured by a biochemical assay. Cell motility was determined using wound healing, while proliferation was determined using MTT assay.Results: LDH-A was expressed in all of the tested cell lines, while LDH-B was specifically expressed only in normal and endocrine-resistant breast cancer cells. This was correlated with significantly enhanced LDH activity and lactate production in endocrine resistant breast cancer cells when compared to normal or endocrine responsive cancer cells. LDH-A or -B knockdown significantly reduced LDH activity and lactate production, which led to reduced cell motility. Exogenous lactate supplementation enhanced cell motility co-incident with enhanced phosphorylation of ERK1/2 and reduced E-cadherin expression. Also, LDH-A or -B knockdown reduced ERK 1/2 phosphorylation.Conclusion: Enhanced cell motility in endocrine resistant breast cancer cells is at least in part mediated by enhanced extracellular lactate levels, and LDH inhibition might be a promising therapeutic target to inhibit cancer cell motility.
Graphene Based Triboelectric Nanogenerators Using Water Based Solution Process
Authors: Domingos Ismael , Neves Ana I. S. , Craciun Monica F. , Alves Helena 
Published: October 2021

A rapid development in personal electronics has raised challenging requirements for portable and sustainable power sources. For example, in wearable technologies, the concept of wearable body area network brings body motion and vital signs monitoring together in synergy. For this, a key aspect is sustainable portable energy, available anywhere, at any time, as generated by triboelectric nanogenerators (TENG). This technology usually demands high-cost processes and materials and still suffer from low power output, as well as unstable output values due to charge generating stimulus with variable intensities. In this work, we present TENGs using shear exfoliated graphene as electrodes as well as active triboelectric layer deposited by a simple solution process. Graphene in combination with polymers such as polydimethylsiloxane (PDMS) were used to produce TENG devices using low-cost solution processing methods. Device electrical power generation was tested with a cyclic physical stimulus for better control and understanding of device output. The triboelectric response of these materials showed open circuit voltages (Voc) and short-circuit currents (Isc)of approximately 233 V and 731 nA respectively when stimulated at 1.5 Hz. A power density of 13.14 μW/cm2 under a load of 200 MΩ was achieved, which can be 40 times higher when compared to devices made with aluminum and PDMS. These results demonstrate the potential of solution process for low-cost triboelectric devices for self-sustainable wearable portable nanogenerators on health and security applications using contact and positional sensors.