bluuebunny/crossref_metadata_2025 huggingface dataset:
The Great Teacher: The Indonesian Adolescent Student Voice
Authors: Suyatno Suyatno , Wantini Wantini , Prastowo Andi , Nuryana Zalik , Firdausi Dzihan Khilmi Ayu , Samaalee Abdunrorma
Published: January 2022

The consensus on professional teachers is known to be mostly determined by external parties, especially the government. This prompts professionalism to be considered as an indicator for the need of a great performance in educational sector. However, this consensus method of assessment is of a great disadvantage, because it negates the scope of professionalism. This study aims to use students’ perspectives in conceptualizing the characteristics of professional teachers. Fifteen students were selected as subjects from secondary schools in Yogyakarta city, Indonesia. Two interviews were conducted via electronic media (email and zoom), in order to share their experiences about the characteristics of professional teachers in schools. Also, an interpretive phenomenological analysis was used to analyze the data, in order to understand the participants’ point of view. The results showed that interpersonal relationships, pleasant personalities, and teaching skills, represented the main characteristics of great teachers, according to the students perspectives. These results recommended the importance of emphasizing teacher-student interpersonal relationships, in order to achieve sustainable professional programs.
Remote Sensing and Hydrologic-Hydrodynamic Modeling Integrated Approach for Rainfall-Runoff Simulation in Farm Dam Dominated Basin
Authors: Xu Chaowei , Han Ziyan , Fu Hao
Published: January 2022

Farm dams may exert various pressures on the flow network depending on the position and scale, which may influence the magnitude, timing, and duration of the flow in the basin. Considering the cumulative effects of farm dams is important for understanding their spatial impacts on the rainfall-runoff process. However, a few studies have been able to reckon the temporal and spatial variation in the flow. In this study, we developed an integrated approach based on remote sensing and hydrologic–hydrodynamic modeling to simulate the rainfall-runoff process in a farm dam-dominated basin. Compared with the classical Xinanjiang model (XAJ), the developed coupled hydrological–hydrodynamic model (coupled-XAJ) shows improved performance in the simulation of the no-linear confluence process in terms of flood flow and peak appearance time. It demonstrates that water retention of multiple farm dams is eminent and that the developed model is effective and feasible in farm dam-dominated basins. Furthermore, the integrated approach enables to control and utilize the rain and flood resources with the safety of arm dams guaranteed. This study provides an innovative method for the scientific management of water resources under the influence of human activities and environmental changes.
Niche Divergence at Intraspecific Level in the Hyrcanian Wood Frog, Rana pseudodalmatina: A Phylogenetic, Climatic, and Environmental Survey
Authors: Vaissi Somaye , Rezaei Sahar
Published: January 2022

The role of ecological niche divergence in lineage speciation has recently stimulated the interest of evolutionary biologists and ecologists. Phylogenetic analysis has revealed that the Hyrcanian wood frog,Rana pseudodalmatina, has diverged into two western and eastern regional clades (WRC and ERC) within the Hyrcanian forest. The goal of this study was to investigate whether the ecological niches of WRC and ERC are conserved or diverged, as well as to figure out what variables promote niche conservatism or divergence. For this purpose, the maximum entropy model was employed to assess environmental niche modeling in geographical (G) space utilizing climatic and macro-environmental data. The niche overlap, equivalency, and similarity tests based on PCAenvanalyses were used to assess niche divergence or conservatism in environmental (E) space. The findings strongly support the hypothesis that WRC and ERC have undergone substantial niche divergence and are constrained by a unique set of climatic and macro-environmental conditions. This study by ecological niche comparisons based on phylogenetic data provides new insights into the exploration of species diversification processes in the Hyrcanian forests.
Association Between TNF-α-308, +489, −238 Polymorphism, and COPD Susceptibility: An Updated Meta-Analysis and Trial Sequential Analysis
Authors: Xia Zhiyu , Wang Yufei , Liu Fu , Shu Hongxin , Huang Peng
Published: January 2022

The tumor necrosis factor alpha (TNF-α) polymorphism may play an important role in chronic obstructive pulmonary disease (COPD) susceptibility. However, the results are still inconclusive. Eligible studies were searched in Cochrane Library database, EMBASE, Pudmed, Web of science, China National Knowledge Infrastructure, and Wanfang database. Finally, a total of 27 case-control studies with 3473 COPD cases and 4935 controls were included in the present analysis. We also performed trial sequential analysis (TSA) to confirm our results. Overall, association between TNF-α-308G/A polymorphism and COPD susceptibility was identified in allelic model (A vs. G, OR = 1.21, 95%CI: 1.01–1.45, p = 0.04) when smoking status was not adjusted. In ethnicity subgroup analysis, we found that the TNF-α -308G/A polymorphism was associated to COPD among Asians (GA vs. GG, OR = 1.35, 95%CI: 1.04–1.77, p = 0.02) when smoking status was not adjusted. However, no significant association was found in Asian smokers or Caucasian smokers. In conclusion, our study suggest that TNF-α-308 GA genotype is related to COPD in the Asian population. In addition, the TNF-α+489G/A, - 238G/A variants do not increase the risk of COPD.

Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021273980.
A Prognostic Model Based on Nine DNA Methylation-Driven Genes Predicts Overall Survival for Colorectal Cancer
Authors: Feng Zhongsheng , Liu Zhanju , Peng Kangsheng , Wu Wei
Published: January 2022

Background: Colorectal cancer (CRC) is the third most frequently diagnosed malignancy and the fourth leading cause of cancer-related death among common tumors in the world. We aimed to establish and validate a risk assessment model to predict overall survival (OS) for the CRC patients.

Methods: DNA methylation-driven genes were identified by integrating DNA methylation profile and transcriptome data from The Cancer Genome Atlas (TCGA) CRC cohort. Then, a risk score model was built based on LASSO, univariable Cox and multivariable Cox regression analysis. After analyzing the clinicopathological factors, a nomogram was constructed and assessed. Another cohort from GEO was used for external validation. Afterward, the molecular and immune characteristics in the two risk score groups were analyzed.

Results: In total, 705 methylation-driven genes were identified. Based on the LASSO and Cox regression analyses, nine genes, i.e., LINC01555, GSTM1, HSPA1A, VWDE, MAGEA12, ARHGAP, PTPRD, ABHD12B and TMEM88, were selected for the development of a risk score model. The Kaplan–Meier curve indicated that patients in the low-risk group had considerably better OS (P = 2e-08). The verification performed in subgroups demonstrated the validity of the model. Then, we established an OS-associated nomogram that included the risk score and significant clinicopathological factors. The concordance index of the nomogram was 0.81. A comprehensive molecular and immune characteristics analysis showed that the high-risk group was associated with tumor invasion, infiltration of immune cells executing pro-tumor suppression (such as myeloid-derived suppressor cells, regulatory T cells, immature dendritic cells) and higher expression of common inhibitory checkpoint molecules (ICPs).

Conclusion: Our nine-gene associated risk assessment model is a promising signature to distinguish the prognosis for CRC patients. It is expected to serve as a predictive tool with high sensitivity and specificity for individualized prediction of OS in the patients with CRC.
Maternal Nutrition During Late Gestation and Lactation: Association With Immunity and the Inflammatory Response in the Offspring
Authors: Li Qihui , Yang Siwang , Zhang Xiaoli , Liu Xinghong , Wu Zhihui , Qi Yingao , Guan Wutai , Ren Man , Zhang Shihai
Published: January 2022

The immature immune system at birth and environmental stress increase the risk of infection in nursing pigs. Severe infection subsequently induces intestinal and respiratory diseases and even cause death of pigs. The nutritional and physiological conditions of sows directly affect the growth, development and disease resistance of the fetus and newborn. Many studies have shown that providing sows with nutrients such as functional oligosaccharides, oils, antioxidants, and trace elements could regulate immunity and the inflammatory response of piglets. Here, we reviewed the positive effects of certain nutrients on milk quality, immunoglobulin inflammatory response, oxidative stress, and intestinal microflora of sows, and further discuss the effects of these nutrients on immunity and the inflammatory response in the offspring.
Tracking Immunoglobulin Repertoire and Transcriptomic Changes in Germinal Center B Cells by Single-Cell Analysis
Authors: Corinaldesi Clarissa , Holmes Antony B. , Shen Qiong , Grunstein Eli , Pasqualucci Laura , Dalla-Favera Riccardo , Basso Katia
Published: January 2022

In response to T-cell-dependent antigens, mature B cells in the secondary lymphoid organs are stimulated to form germinal centers (GCs), which are histological structures deputed to antibody affinity maturation, a process associated with immunoglobulin gene editing by somatic hypermutation (SHM) and class switch recombination (CSR). GC B cells are heterogeneous and transition across multiple stages before being eliminated by apoptosis or committing to post-GC differentiation as memory B cells or plasma cells. In order to explore the dynamics of SHM and CSR during the GC reaction, we identified GC subpopulations by single-cell (sc) transcriptomics and analyzed the load of immunoglobulin variable (V) region mutations as well as the isotype class distribution in each subpopulation. The results showed that the large majority of GC B cells display a quantitatively similar mutational load in the V regions and analogous IGH isotype class distribution, except for the precursors of memory B cells (PreM) and plasma cells (PBL). PreM showed a bimodal pattern with about half of the cells displaying high V region germline identity and enrichment for unswitched IGH, while the rest of the cells carried a mutational load similar to the bulk of GC B cells and showed a switched isotype. PBL displayed a bias toward expression of IGHG and higher V region germline identity compared to the bulk of GC B cells. Genes implicated in SHM and CSR were significantly induced in specific GC subpopulations, consistent with the occurrence of SHM in dark zone cells and suggesting that CSR can occur within the GC.
A Manipulative Field Experiment to Evaluate the Impact of Discarded Plastic Bags on Shallow Vegetated Benthic Communities
Authors: Torn Kaire , Martin Georg , Paalme Tiina , Reisalu Greta
Published: January 2022

Coastal regions are biologically active areas with significant ecological and socioeconomic values. These regions are increasingly being affected by marine litter. The impact of macro-sized marine litter on biomass and net primary production of hard and soft bottom communities was investigated by using a manipulative field experiment. Plastic bags were used to mimic the disturbance caused by litter to benthic vegetation and fauna. The experiment was carried out on a soft substrate community dominated by sago pondweed Stuckenia pectinata (L.) Boerner and bladder wrack Fucus vesiculosus L. as a foundation species of a hard substrate. A rapid negative impact of the plastic bag cover on vegetation biomass of soft-bottom community was detected, while the impact on the biomass of hard bottom vegetation was non-significant. Plastic bag cover substantially reduced the net production rates of hard substrate species Fucus and the biomass of associated zoobenthos. The difference in net production rates of Stuckenia with and without plastic cover was negligible.
Cholecalciferol vs. Small Doses of Alfacalcidol vs. Placebo in Chronic Kidney Disease Patients on Hemodialysis: A Randomized Parallel Group Study
Authors: Matuszkiewicz-Rowińska Joanna , Kulicki Paweł , Zebrowski Paweł , Klatko Wiesław , Sokalski Antoni , Niemczyk Stanisław , Wypych-Birecka Magdalena , Małyszko Jolanta
Published: January 2022

Background

The ability of extrarenal tissues to convert 25(OH)D (calcidiol) into 1,25(OH)2D (calcitriol) and dependence of the conversion on substrate levels provide the rationale for supplementing vitamin D in dialysis patients who usually have severe depletion of both: 25(OH)D and 1,25(OH)2D. The primary aim of the study was to compare effects of small doses of cholecalciferol (12,000 IU/week) with frequently used in Europe, small doses of alfacalcidol (1.5 μg/week) or placebo, given for 12 weeks, on serum 1,25(OH)2D in hemodialysis patients with 25(OH)D deficiency. Secondary outcomes were changes in serum calcium, phosphate, 25(OH)D, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23) and sclerostin during the treatment.

Methods

This was a prospective, randomized, partly double-blind (cholecalciferol vs. placebo) study. Out of 522 patients dialyzed in 5 centers in the Mazovian Province, 93 gave informed consent and met the inclusion criteria: any vitamin D metabolites and calcimimetics naïve; no history of liver or intestinal disease; serum 25(OH)D <20 ng/ml, iPTH <1,000 –>110 pg/ml, calcium <10.2, and phosphate <6.8 mg/dl. The subjects were stratified by serum iPTH, then randomized into 3 groups according to the treatment.

Results

To our knowledge, this is the first study comparing head-to-head these drugs in the hemodialysis population. There were no significant differences between the groups at baseline. 81 patients completed the study. Cholecalciferol normalized serum 25(OH)D, with a mean rise from 12.9 ± 6.7 to 31.3 ± 10.1 ng/ml (p < 0.0001). This was accompanied by a marked increase of 1,25(OH)2D from 13.8 ± 9.3 to 25.1 ± 14.2 pmol/l (p < 0.0001). A rise in serum 1,25(OH)2D was also observed in alfacalcidol treated patients, however much smaller (from 13.5 ± 10.1 to 18.5 ± 11.0 pmol/l; p = 0.02). Neither cholecalciferol nor alfacalcidol treatment resulted in significant changes in serum PTH and the remaining parameters.

Conclusions

In most patients, treatment with cholecalciferol in a 12,000 IU/week dose permits safe correction of 25(OH)D deficiency and is more effective than 1.5 μg/week dose of alfacalcidol in rising serum 1,25(OH)2D. This, together with a lack of influence on circulating iPTH the usefulness of such small alfacalcidol doses in hemodialysis patients is debatable.
Highly Engaged Video-Watching Pattern in Asynchronous Online Pharmacology Course in Pre-clinical 4th-Year Medical Students Was Associated With a Good Self-Expectation, Understanding, and Performance
Authors: Wang Jann-Yuan , Yang Chia-Hsien , Liao Wei-Chih , Yang Kai-Chien , Chang I-Wen , Sheu Bor-Ching , Ni Yen-Hsuan
Published: January 2022

Background

Online video-based learning is more common in higher education. Investigating students' viewing behaviors while watching online video lectures is essential for instructors to understand their learning status so that the course content, structure, and media selection can be improved continuously. The current study identified the engagement level of the learners based on their online video-watching behaviors, and tested the correlation between the engagement level and learning outcome.

Methods

The action logs of watching online video lectures in 2020 Spring Pharmacology of the 4th-year medical students of the 6-year course and their feedbacks by questionnaires after each exam during the semester were provided anonymously. The data were analyzed and visualized for an efficient way to comprehend and interpret. To define the student's engagement level in his or her video-based learning journey, three viewing criteria, “Completion,” “Pausing,” and “Repeated watching” were identified. We evaluated the association between the engagement level and the students' learning outcomes, including their learning satisfaction, knowledge acquisition progresses based on assessment results, and the grades measured by the instructors.

Results

The graphs and the charts demonstrate whether the students allocated enough time to finish the video lectures (completion), paused for a while, then resumed the video (pausing), or replayed the specific sections of video content (repeated watching). The engagement level with video lectures, evaluated by pre-defined thresholds for “Completion,” “Pausing,” and “Repeated watching” had a positive correlation with the learning outcomes.

Conclusions

We suggested that an engagement dashboard containing real-time visualized information on students' online video-watching behaviors can be developed to help instructors to monitor students' learning progress and improve teaching in a timely fashion. It can also help each student to re-feel the stimulation of peers, prompt self-monitoring, improve their learning attitudes and disciplines for better learning outcomes. This innovative way of assessing student's engagement during online video-based learning can also be used for quality assurance purposes.
ANCA-Associated Vasculitis With Anti-GBM Disease and Two Types of Tumors: A Case Report
Authors: Li Xiuxiu , Huang Meichun , Liu Jun
Published: January 2022

Introduction

Anti-neutrophil cytoplasm antibody (ANCA)-associated-vasculitis and anti-glomerular basement membrane (GBM) disease are types of autoimmune diseases that are characterized by the presence of circulating autoantibodies. Most patients with these diseases experience sudden onset, rapid progress, and poor prognosis. The purpose of the present article is to report a case of ANCA-associated vasculitis with anti-GBM disease and two types of tumors.

Case Report

A 63-year-old Chinese woman who underwent resection for rectal cancer 6 years before and for lung adenocarcinoma 4 years before, presented with fever and nasal obstruction, for the past 2 months and chondritis of an ear for the past 1 month. The patient failed to respond to an anti-infection treatment at local and higher-level hospitals with the first episode of “recurrent sinusitis and fever.” Later, systemic symptoms such as fatigue, numbness of the limbs, and auricular chondritis gradually aggravated, followed by an increase in inconspicuous hematuria, proteinuria, and serum creatinine level. After admission, the GBM antibody, C-ANCA, and PR3 were positive. The renal puncture was diagnosed as anti-glomerular basement membrane antibody disease. After treatment, her serum creatinine decreased to 104 umol/l.

Discussion

In the present report, we introduced the case of a rare double-positive disease in a patient with two types of tumors. Importantly, we noted that colon cancer and lung cancer, PR3, and anti-GBM disease may be related to their pathogenesis and manifestations. Further research is warranted to confirm these hypotheses.
Influence of Comorbidities and Airway Clearance on Mortality and Outcomes of Patients With Severe Bronchiectasis Exacerbations in Taiwan
Authors: Huang Hung-Yu , Chung Fu-Tsai , Lin Chun-Yu , Lo Chun-Yu , Huang Yu-Tung , Huang Yu-Chen , Lai Yu-Te , Gan Shu-Ting , Ko Po-Chuan , Lin Horng-Chyuan , Chung Kian Fan , Wang Chun-Hua
Published: January 2022

Bronchiectasis is characterized by systemic inflammation and multiple comorbidities. This study aimed to investigate the clinical outcomes based on the bronchiectasis etiology comorbidity index (BACI) score in patients hospitalized for severe bronchiectasis exacerbations. We included non-cystic fibrosis patients hospitalized for severe bronchiectasis exacerbations between January 2008 and December 2016 from the Chang Gung Research Database (CGRD) cohort. The main outcome was the 1-year mortality rate after severe exacerbations. We used the Cox regression model to assess the risk factors of 1-year mortality. Of 1,235 patients who were hospitalized for severe bronchiectasis exacerbations, 641 were in the BACI < 6 group and 594 in the BACI ≥ 6 group. The BACI ≥ 6 group had more previous exacerbations and a lower FEV1. Pseudomonas aeruginosa (19.1%) was the most common bacterium, followed by Klebsiella pneumoniae (7.5%). Overall, 11.8% of patients had respiratory failure and the hospital mortality was 3.0%. After discharge, compared to the BACI < 6 group, the BACI ≥ 6 group had a significantly higher cumulative incidence of respiratory failure and mortality in a 1-year follow-up. The risk factors for 1-year mortality in a multivariate analysis include age [hazard ratio (HR) 4.38, p = 0.01], being male (HR 4.38, p = 0.01), and systemic corticosteroid usage (HR 6.35, p = 0.001), while airway clearance therapy (ACT) (HR 0.50, p = 0.010) was associated with a lower mortality risk. An increased risk of respiratory failure and mortality in a 1-year follow-up after severe exacerbations was observed in bronchiectasis patients with multimorbidities, particularly older age patients, male patients, and patients with a history of systemic corticosteroid use. ACT could effectively improve the risk for 1-year mortality.
Relationships Among Cognitive Function, Frailty, and Health Outcome in Community-Dwelling Older Adults
Authors: Xue Huiping , Huang Chunxia , Zhu Qin , Zhou Shuixin , Ji Yunlan , Ding Xiaohui , Zhang Dandan , Gu Dongmei
Published: January 2022

Background

Frailty and cognitive impairment are significant problems faced by older adults, which have a significant impact on their activities of daily living, social activities, and quality of life.

Design

Cross-sectional study.

Methods

A total of 252 older adults in two communities in Yangzhou were randomly selected. The cognitive function of the elderly was assessed using the Memory and Executive Screening (MES). The frailty phenotype was used to evaluate the frail situation of older adults. The activity of daily living (ADL), functional activities questionnaire (FAQ), and European quality of 5-dimensions (EQ-5D) were used to evaluate health outcomes in the elderly. SEM was used to explore the direct and indirect relationship among cognitive function, frailty and health outcomes.

Results

There was a significant direct correlation between cognitive function and frailty; the direct effect was −0.521. The influence path of cognitive function on health outcomes included direct and indirect effects; the total effect was −0.759. The effect of frailty on health outcomes included direct and indirect effects; the total effect was 0.440.

Conclusion

According to SEM, cognitive function interacts with frailty and may reduce the quality of life, the ADL, and social activities among older adults directly and indirectly, so future assessments of older adults should consider both cognitive function and frailty, so as to further improve the health outcome of the elderly. When formulating relevant intervention measures in the future, we need to consider that it cannot only improve the cognitive function, but also improve the frail situation, so as to jointly improve the health outcomes of older adults.
Regular Practice of Autogenic Training Reduces Migraine Frequency and Is Associated With Brain Activity Changes in Response to Fearful Visual Stimuli
Authors: Dobos Dóra , Szabó Edina , Baksa Dániel , Gecse Kinga , Kocsel Natália , Pap Dorottya , Zsombók Terézia , Kozák Lajos R. , Kökönyei Gyöngyi , Juhász Gabriella
Published: January 2022

Several factors can contribute to the development and chronification of migraines, including stress, which is undoubtedly a major trigger. Beyond pharmacotherapy, other treatment methods also exist, including behavioral techniques aiming at reducing patients’ stress response. However, the exact brain mechanisms underlying the efficacy of such methods are poorly understood. Our pilot study examined whether the regular practice of autogenic training (AT) induces functional brain changes and if so, how it could be associated with the improvement of migraine parameters. By exploring neural changes through which AT exerts its effect, we can get closer to the pathomechanism of migraine. In particular, we investigated the effect of a headache-specific AT on brain activation using an implicit face emotion processing functional MRI (fMRI) task in female subjects with and without episodic migraine. Our focus was on migraine- and psychological stress-related brain regions. After a 16-week training course, migraineurs showed decreased activation in the migraine-associated dorsal pons to fearful compared with neutral visual stimuli. We also detected decreasing differences in supplementary motor area (SMA) activation to fearful stimuli, and in posterior insula activation to happy stimuli between healthy subjects and migraineurs. Furthermore, migraineurs reported significantly less migraine attacks. These brain activation changes suggest that AT may influence the activity of brain regions responsible for emotion perception, emotional and motor response integration, as well as cognitive control, while also being able to diminish the activation of regions that have an active role in migraine attacks. Improvements induced by the training and the underlying neurophysiological mechanisms are additional arguments in favor of evidence-based personalized behavioral therapies.
Role of Probiotics in Halitosis of Oral Origin: A Systematic Review and Meta-Analysis of Randomized Clinical Studies
Authors: López-Valverde Nansi , López-Valverde Antonio , Macedo de Sousa Bruno , Rodríguez Cinthia , Suárez Ana , Aragoneses Juan Manuel
Published: January 2022

Halitosis or oral malodor is a condition caused by the putrefaction of sulfur-containing amino acids. It affects 30–50% of the population and causes social rejection, reducing quality of life, and self-esteem. Probiotics, especially Lactobacillus species, have been proposed for the treatment of genuine halitosis, due to their ability to reduce bacterial colonization. Our objective was to evaluate their use for the treatment of oral halitosis. Applying the PRISMA statement guidelines, we searched PubMed, EMBASE, and Web of Science databases for scientific articles from the last 15 years, up to July 2021. The keywords used were “Probiotics”; “Halitosis”; “Mouth diseases”; “Oral health”; “Humans”; “Randomized Clinical Trials” according to the question, “Are probiotics effective for the reduction or elimination of oral halitosis?” Fourteen studies were identified, although only four met the inclusion criteria. We evaluated 283 participants treated with two different probiotics, with a follow-up of at least 2 weeks. Risk of bias was assessed using the Cochrane Collaboration tool. A fixed-effects meta-analysis was performed. No statistical significance was found (p = 0.53). Despite the limitations of this meta-analysis, we believe that some probiotics have a beneficial effect on halitosis, although more clinical trials are needed to establish real evidence on this aspect.

Systematic Review Registration:https://doi.org/10.37766/inplasy2021.9.0009, identifier: INPLASY20211900.
Neutralizing Anti-IL-17A Antibody Demonstrates Preclinical Activity Enhanced by Vinblastine in Langerhans Cell Histiocytosis
Authors: Åkefeldt Selma Olsson , Ismail Mohamad Bachar , Belot Alexandre , Salvatore Giulia , Bissay Nathalie , Gavhed Désirée , Aricò Maurizio , Henter Jan-Inge , Valentin Hélène , Delprat Christine
Published: January 2022

Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm characterised by the accumulation into granulomas of apoptosis-resistant pathological dendritic cells (LCH-DCs). LCH outcome ranges from self-resolving to fatal. Having previously shown that, (i) monocyte-derived DCs (Mo-DCs) from LCH patients differentiate into abnormal and pro-inflammatory IL-17A-producing DCs, and (ii) recombinant IL-17A induces survival and chemoresistance of healthy Mo-DCs, we investigated the link between IL-17A and resistance to apoptosis of LCH-DCs. In LCH granulomas, we uncovered the strong expression of BCL2A1 (alias BFL1), an anti-apoptotic BCL2 family member. In vitro, intracellular IL-17A expression was correlated with BCL2A1 expression and survival of Mo-DCs from LCH patients. Based on the chemotherapeutic drugs routinely used as first or second line LCH therapy, we treated these cells with vinblastine, or cytarabine and cladribine. Our preclinical results indicate that high doses of these drugs decreased the expression of Mcl-1, the main anti-apoptotic BCL2 family member for myeloid cells, and killed Mo-DCs from LCH patients ex vivo, without affecting BCL2A1 expression. Conversely, neutralizing anti-IL-17A antibodies decreased BCL2A1 expression, the downregulation of which lowered the survival rate of Mo-DCs from LCH patients. Interestingly, the in vitro combination of low-dose vinblastine with neutralizing anti-IL-17A antibodies killed Mo-DCs from LCH patients. In conclusion, we show that BCL2A1 expression induced by IL-17A links the inflammatory environment to the unusual pro-survival gene activation in LCH-DCs. Finally, these preclinical data support that targeting both Mcl-1 and BCL2A1 with low-dose vinblastine and anti-IL-17A biotherapy may represent a synergistic combination for managing recurrent or severe forms of LCH.
Can Routine Blood and Urine Parameters Reveal Clues to Detect Bladder Cancer? A Case–Control Study
Authors: Wang Dan-Qi , Shuai Juan , Zheng Hang , Guo Zhong-Qiang , Huang Qiao , Xu Xiao-Feng , Li Xiao-Dong , Zi Hao , Ming Dao-Jing , Ren Xuan-Yi , Zeng Xian-Tao
Published: January 2022

Objective

Limited attention has been paid to abnormal blood and urine test results for patients with bladder cancer. The present study aimed to identify whether blood and urine parameters are associated with bladder cancer.

Methods

We used a case–control design and matched each patient with bladder cancer with three healthy controls of the same age and sex. Univariate conditional logistic regression was used to calculate the crude and adjusted odds ratio (OR) and its 95% CI. Multivariate conditional logistic regression was performed for confounders adjustment, and Spearman’s correlation coefficient was used to assess the correlation between tumor T stages and urine parameters.

Results

Patients with bladder cancer (n = 360) and controls (n = 1050) were recruited. In the univariate conditional logistic analysis, higher urine pH was associated with a decreased risk of bladder cancer (OR = 0.67, 95% CI = 0.57–0.78), while higher values of urine protein (OR = 4.55, 95% CI = 3.36–6.15), urine glucose (OR = 1.56, 95% CI = 1.18–2.05), and urine occult blood (OR = 4.27, 95% CI = 3.44–5.29) were associated with an increased risk of bladder cancer. After adjustment for body mass index, fasting blood glucose, hypertension, red blood cells, white blood cells, lymphocytes, neutrophils, and platelets, significance still remained for urine pH (OR = 0.68, 95% CI = 0.53–0.88), urine protein (OR = 1.97, 95% CI = 1.21–3.19), urine glucose (OR = 2.61, 95% CI = 1.39–4.89), and urine occult blood (OR = 3.54, 95% CI = 2.73–4.58).

Conclusion

This study indicated that lower urine pH and higher values of urine protein, urine glucose, and urine occult blood might be risk factors for bladder cancer.
The Mutational Landscape of Early-Onset Breast Cancer: A Next-Generation Sequencing Analysis
Authors: Andrikopoulou Angeliki , Chatzinikolaou Spyridoula , Kyriopoulos Ilias , Bletsa Garyfalia , Kaparelou Maria , Liontos Michalis , Dimopoulos Meletios-Athanasios , Zagouri Flora
Published: January 2022

Background

Around 5%–7% of breast cancer cases are diagnosed in women younger than 40, making it the leading cause of female cancer in the 25- to 39-year-old age group. Unfortunately, young age at diagnosis is linked to a more aggressive tumor biology and a worse clinical outcome. The identification of the mutational landscape of breast cancer in this age group could optimize the management.

Methods

We performed NGS analysis in paraffin blocks and blood samples of 32 young patients with breast cancer [<40 years] and 90 older patients during the period 2019 through 2021. All patients were treated in a single institution at the Oncology Department of “Alexandra” Hospital, Medical School, University of Athens, Greece.

Results

Breast tumors were characterized more frequently by HER2 overexpression [25% vs 18.9%], higher ki67 levels [75% vs 61%] and lower differentiation [71.9% vs 60%] in the younger group. PIK3CA [6/20; 30%] and TP53 [6/20; 30%] were the most frequent pathogenic somatic mutations identified in young patients, while one case of BRCA2 somatic mutation [1/20; 5%] and one case of PTEN somatic mutation [1/20; 5%] were also identified. PIK3CA mutations [16/50; 32%] and TP53 mutations [20/50; 40%] were the most common somatic mutations identified in older patients, however other somatic mutations were also reported (ATM, AKT, CHEK2, NRAS, CDKN2A, PTEN, NF1, RB1, FGFR1, ERBB2). As for germline mutations, CHEK2 [3/25; 12%] was the most common pathogenic germline mutation in younger patients followed by BRCA1 [2/25; 8%]. Of note, CHEK2 germline mutations were identified less frequently in older patients [2/61; 3%] among others [BRCA1 (2/61; 3%), ATM (2/61; 3%), APC (1/61; 1,6%) and BRCA2 (1/61; 1,6%)].

Conclusion

We here report the mutational profile identified via NGS in patients with early-onset breast cancer compared to their older counterparts. Although the sample size is small and no statistically significant differences were detected, we highlight the need of genetic testing to most patients in this subgroup.
Mechanical Properties in the Glioma Microenvironment: Emerging Insights and Theranostic Opportunities
Authors: Bhargav Adip G. , Domino Joseph S. , Chamoun Roukoz , Thomas Sufi M.
Published: January 2022

Gliomas represent the most common malignant primary brain tumors, and a high-grade subset of these tumors including glioblastoma are particularly refractory to current standard-of-care therapies including maximal surgical resection and chemoradiation. The prognosis of patients with these tumors continues to be poor with existing treatments and understanding treatment failure is required. The dynamic interplay between the tumor and its microenvironment has been increasingly recognized as a key mechanism by which cellular adaptation, tumor heterogeneity, and treatment resistance develops. Beyond ongoing lines of investigation into the peritumoral cellular milieu and microenvironmental architecture, recent studies have identified the growing role of mechanical properties of the microenvironment. Elucidating the impact of these biophysical factors on disease heterogeneity is crucial for designing durable therapies and may offer novel approaches for intervention and disease monitoring. Specifically, pharmacologic targeting of mechanical signal transduction substrates such as specific ion channels that have been implicated in glioma progression or the development of agents that alter the mechanical properties of the microenvironment to halt disease progression have the potential to be promising treatment strategies based on early studies. Similarly, the development of technology to measure mechanical properties of the microenvironment in vitro and in vivo and simulate these properties in bioengineered models may facilitate the use of mechanical properties as diagnostic or prognostic biomarkers that can guide treatment. Here, we review current perspectives on the influence of mechanical properties in glioma with a focus on biophysical features of tumor-adjacent tissue, the role of fluid mechanics, and mechanisms of mechanical signal transduction. We highlight the implications of recent discoveries for novel diagnostics, therapeutic targets, and accurate preclinical modeling of glioma.
Characterization of aEEG During Sleep and Wakefulness in Healthy Children
Authors: Löffelhardt Verena T. , Della Marina Adela , Greve Sandra , Müller Hanna , Felderhoff-Müser Ursula , Dohna-Schwake Christian , Bruns Nora
Published: January 2022

Introduction

Interpretation of amplitude-integrated EEG (aEEG) is hindered by lacking knowledge on physiological background patterns in children. The aim of this study was to find out whether aEEG differs between wakefulness and sleep in children.

Methods

Forty continuous full-channel EEGs (cEEG) recorded during the afternoon and overnight in patients <18 years of age without pathologies or only solitary interictal epileptiform discharges were converted into aEEGs. Upper and lower amplitudes of the C3–C4, P3–P4, C3–P3, C4–P4, and Fp1–Fp2 channels were measured during wakefulness and sleep by two investigators and bandwidths (BW) calculated. Sleep states were assessed according to the American Academy of Sleep Medicine. Median and interquartile ranges (IQR) were calculated to compare the values of amplitudes and bandwidth between wakefulness and sleep.

Results

Median age was 9.9 years (IQR 6.1–14.7). All patients displayed continuous background patterns. Amplitudes and BW differed between wakefulness and sleep with median amplitude values of the C3–C4 channel 35 μV (IQR: 27–49) for the upper and 13 μV (10–19) for the lower amplitude. The BW was 29 μV (21–34). During sleep, episodes with high amplitudes [upper: 99 μV (71–125), lower: 35 μV (25–44), BW 63 μV (44–81)] corresponded to sleep states N2–N3. High amplitude-sections were interrupted by low amplitude-sections, which became the longer toward the morning [upper amplitude: 39 μV (30–51), lower: 16 μV (11–20), BW 23 μV (19–31)]. Low amplitude-sections were associated with sleep states REM, N1, and N2. With increasing age, amplitudes and bandwidths declined.

Conclusion

aEEGs in non-critically ill children displayed a wide range of amplitudes and bandwidths. Amplitudes were low during wakefulness and light sleep and high during deep sleep. Interpretation of pediatric aEEG background patterns must take into account the state of wakefulness in in clinical practice and research.
Role of Extracorporeal Membrane Oxygenation in Adults and Children With Refractory Septic Shock: A Systematic Review and Meta-Analysis
Authors: Yang Yufan , Xiao Zhenghui , Huang Jiaotian , Gong Ling , Lu Xiulan
Published: January 2022

Background

The benefits of extracorporeal membrane oxygenation in patients with refractory septic shock remain controversial. Current guidelines on the management of refractory septic shock recommend the consideration of extracorporeal membrane oxygenation as a salvage therapy. The difference between adults and children with septic refractory shock treated with extracorporeal membrane oxygenation has not been previously analyzed. We aimed to review peer-reviewed publications on the role of extracorporeal membrane oxygenation in adults and children with refractory septic shock.

Methods

Studies reporting on mortality in both adults and children with refractory septic shock supported with extracorporeal membrane oxygenation published in PubMed, Cochrane Library, and Embase databases were included in the meta-analysis. Study eligibility was independently assessed by two authors, and disagreements were resolved by a third author. The outcome measure was survival at discharge. Subgroup analysis included the adult and pediatric groups.

Results

Of the 293 articles screened, 14 original articles were identified for systematic review and meta-analysis. The cumulative estimate of survival (14 studies, 535 patients) in the cohort was 39% (95% confidence interval [CI]: 27–51%). During the subgroup analysis, the cumulative estimate of survival at discharge in the adult group (6 studies, 276 patients) in the cohort was 18% (95% CI: 10–27%), and that in the pediatric group (8 studies, 259 patients) was 53% (95% CI: 47–59%).

Conclusions

The survival rate of adults with refractory septic shock requiring extracorporeal membrane oxygenation was 18%, and children with refractory septic shock requiring extracorporeal membrane oxygenation had a higher survival rate (53%) than adults.
Rivastigmine Regulates the HIF-1α/VEGF Signaling Pathway to Induce Angiogenesis and Improves the Survival of Random Flaps in Rats
Authors: Liu Yingying , Li Wenjie , Ma Xinyi , He Jibing , Lin Yi , Lin Dingsheng
Published: January 2022

Random skin flaps are frequently used to repair skin damage. However, the ischemic and hypoxic necrosis limits their wider application. Rivastigmine, a carbamate cholinesterase inhibitor (ChEI), has also been shown to reduce ischemia–reperfusion injury (IRI) and inflammation. This study was performed to examine the effect of rivastigmine on flap survival. Sixty male Sprague–Dawley rats with a modified McFarland flap were randomly divided into three groups: control group, 1 ml of solvent (10% DMSO + 90% corn oil); low-dose rivastigmine group (Riv-L), 1.0 mg/kg; and high-dose rivastigmine group (Riv-H), 2.0 mg/kg. All rats were treated once a day. On day 7, the skin flap survival area was measured. After staining with hematoxylin and eosin (H&E), the pathological changes and microvessel density (MVD) were examined. The expression of inflammatory factors IL-1β and IL-18, CD34, hypoxia-inducible factor-1α (HIF-1α), and vascular endothelial growth factor (VEGF) was examined by immunohistochemical staining. The malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were examined to determine the degree of oxidative stress. Lead oxide/gelatin angiography showed neovascularization and laser Doppler blood flowmetry showed the blood filling volume. Rivastigmine significantly increased the flap survival area and improved neovascularization. CD34, VEGF, and HIF-1α expression were increased, These changes were more pronounced in the Riv-H group. Treatment with rivastigmine reduced the level of MDA, improved SOD activity, and reduced expression of IL-1β and IL-18. Our results indicate that Rivastigmine can increase angiogenesis and significantly improve flap survival.
Phase Diagram of Nickelate Superconductors Calculated by Dynamical Vertex Approximation
Authors: Held Karsten , Si Liang , Worm Paul , Janson Oleg , Arita Ryotaro , Zhong Zhicheng , Tomczak Jan M. , Kitatani Motoharu
Published: January 2022

We review the electronic structure of nickelate superconductors with and without effects of electronic correlations. As a minimal model, we identify the one-band Hubbard model for the Ni 3dx2−y2 orbital plus a pocket around the A-momentum. The latter, however, merely acts as a decoupled electron reservoir. This reservoir makes a careful translation from nominal Sr-doping to the doping of the one-band Hubbard model mandatory. Our dynamical mean-field theory calculations, in part already supported by the experiment, indicate that the Γ pocket, Nd 4f orbitals, oxygen 2p, and the other Ni 3d orbitals are not relevant in the superconducting doping regime. The physics is completely different if topotactic hydrogen is present or the oxygen reduction is incomplete. Then, a two-band physics hosted by the Ni 3dx2−y2 and 3d3z2−r2orbitals emerges. Based on our minimal modeling, we calculated the superconducting Tc vs. Sr-doping x phase diagram prior to the experiment using the dynamical vertex approximation. For such a notoriously difficult to determine quantity as Tc, the agreement with the experiment is astonishingly good. The prediction that Tc is enhanced with pressure or compressive strain has been confirmed experimentally as well. This supports that the one-band Hubbard model plus an electron reservoir is the appropriate minimal model.
Mueller Matrix Ellipsometric Approach on the Imaging of Sub-Wavelength Nanostructures
Authors: Käseberg Tim , Grundmann Jana , Siefke Thomas , Klapetek Petr , Valtr Miroslav , Kroker Stefanie , Bodermann Bernd
Published: January 2022

Conventional spectroscopic ellipsometry is a powerful tool in optical metrology. However, when it comes to the characterization of non-periodic nanostructures or structured fields that are much smaller than the illumination spot size, it is not well suited as it integrates the results over the whole illuminated area. Instead, imaging ellipsometry can be applied. Especially imaging Mueller matrix ellipsometry is highly useful in nanostructure characterization and defect inspection, as it is capable to measure the complete Mueller matrix for each pixel in a microscope image of the sample. It has been shown that these so-called Mueller matrix images can help to distinguish geometrical features of nanostructures in the sub-wavelength regime due to visible differences in off-diagonal matrix elements. To further investigate the sensitivity of imaging Mueller matrix ellipsometry for sub-wavelength sized features, we designed and fabricated a sample containing geometrical nanostructures with lateral dimensions ranging from 50 to 5,000 nm. The structures consist of square and circular shapes with varying sizes and corner rounding. For the characterization of their Mueller matrix images, we constructed an in-house Mueller matrix microscope capable of measuring the full Mueller matrix for each pixel of a CCD camera, using an imaging system and a dual-rotating compensator configuration for the ellipsometric system. The samples are illuminated at 455 nm wavelength and the measurements can be performed in both transmission and reflection. Using this setup, we systematically examine the sensitivity of Mueller matrix images to small features of the designed nanostructures. Within this contribution, the results are compared with traceable atomic force microscopy measurements and the suitability of this measurement technique in optical nanometrology is discussed. AFM measurements confirm that the fabricated samples closely match their design and are suitable for nanometrological test measurements. Mueller matrix images of the structures show close resemblance to numerical simulations and significant influence of sub-wavelength features to off-diagonal matrix elements.
Improved 93-11 Genome and Time-Course Transcriptome Expand Resources for Rice Genomics
Authors: Wang Sen , Gao Shenghan , Nie Jingyi , Tan Xinyu , Xie Junhua , Bi Xiaochun , Sun Yan , Luo Sainan , Zhu Qianhui , Geng Jianing , Liu Wanfei , Lin Qiang , Cui Peng , Hu Songnian , Wu Shuangyang
Published: January 2022

In 2002, the first crop genome was published using the rice cultivar 93-11, which is the progenitor of the first super-hybrid rice. The genome sequence has served as a reference genome for the indica cultivars, but the assembly has not been updated. In this study, we update the 93-11 genome assembly to a gap-less sequence using ultra-depth single molecule real-time (SMRT) reads, Hi-C sequencing, reference-guided, and gap-closing approach. The differences in the genome collinearity and gene content between the 93-11 and the Nipponbare reference genomes confirmed to map the indica cultivar sequencing data to the 93-11 genome, instead of the reference. Furthermore, time-course transcriptome data showed that the expression pattern was consistently correlated with the stages of seed development. Alternative splicing of starch synthesis-related genes and genomic variations of waxy make it a novel resource for targeted breeding. Collectively, the updated high quality 93-11 genome assembly can improve the understanding of the genome structures and functions of Oryza groups in molecular breeding programs.