bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of an Intestinal Microbiota Signature Associated With the Severity of Necrotic Enteritis
Authors: Yang Qing , Liu Jing , Wang Xiaofan , Robinson Kelsy , Whitmore Melanie A. , Stewart Sydney N. , Zhao Jiangchao , Zhang Guolong
Published: August 2021

Necrotic enteritis (NE), an economically devastating disease of poultry caused by pathogenic Clostridium perfringens, is known to induce small intestinal lesions and dysbiosis. However, the intestinal microbes that are associated with NE severity are yet to be characterized. Here, we investigated the link between the ileal microbiota and disease severity in a chicken model of clinical NE using 16S rRNA gene sequencing. Our results indicated that richness and Shannon Index of the ileal microbiota were drastically reduced (p<0.01) as NE was exacerbated. While the relative abundance of C. perfringens increased from 0.02% in healthy chickens to 58–70% in chickens with severe infection, a majority of the ileal microbes were markedly diminished, albeit varying in their sensitivity to NE. Compositionally, a large group of ileal microbes showed a significant correlation with NE severity. Firmicutes, such as group A and B Lactobacillus, Lactobacillus reuteri, Subdoligranulum variabile, Mediterraneibacter, and Staphylococcus as well as two genera of Actinobacteria (Corynebacterium and Kocuria) and two highly related Cyanobacteria were progressively declined as NE was aggravated. Other Firmicutes, such as Weissella, Romboutsia, Kurthia, Cuneatibacter, Blautia, and Aerococcus, appeared much more sensitive and were rapidly abolished in chickens even with mild NE. On the other hand, Enterococcus cecorum and two Escherichia/Shigella species were only enriched in the ileal microbiota of chickens with extremely severe NE, while several other species such as Streptococcus gallolyticus and Bacteroides fragilis remained unaltered by NE. Functionally, secondary bile acid biosynthesis was predicted to be suppressed by NE, while biosynthesis of aromatic and branched-amino acids and metabolism of a majority of amino acids were predicted to be enhanced in the ileum of NE-afflicted chickens. These intestinal microbes showing a strong correlation with NE severity may provide important leads for the development of novel diagnostic or therapeutic approaches to NE and possibly other enteric diseases.
Development and Validation of a Nomogram for the Prediction of Hospital Mortality of Patients With Encephalopathy Caused by Microbial Infection: A Retrospective Cohort Study
Authors: Zhao Lina , Li Yun , Wang Yunying , Gao Qian , Ge Zengzheng , Sun Xibo , Li Yi
Published: August 2021

Background

Hospital mortality is high for patients with encephalopathy caused by microbial infection. Microbial infections often induce sepsis. The damage to the central nervous system (CNS) is defined as sepsis-associated encephalopathy (SAE). However, the relationship between pathogenic microorganisms and the prognosis of SAE patients is still unclear, especially gut microbiota, and there is no clinical tool to predict hospital mortality for SAE patients. The study aimed to explore the relationship between pathogenic microorganisms and the hospital mortality of SAE patients and develop a nomogram for the prediction of hospital mortality in SAE patients.

Methods

The study is a retrospective cohort study. The lasso regression model was used for data dimension reduction and feature selection. Model of hospital mortality of SAE patients was developed by multivariable Cox regression analysis. Calibration and discrimination were used to assess the performance of the nomogram. Decision curve analysis (DCA) to evaluate the clinical utility of the model.

Results

Unfortunately, the results of our study did not find intestinal infection and microorganisms of the gastrointestinal (such as: Escherichia coli) that are related to the prognosis of SAE. Lasso regression and multivariate Cox regression indicated that factors including respiratory failure, lactate, international normalized ratio (INR), albumin, SpO2, temperature, and renal replacement therapy were significantly correlated with hospital mortality. The AUC of 0.812 under the nomogram was more than that of the Simplified Acute Physiology Score (0.745), indicating excellent discrimination. DCA demonstrated that using the nomogram or including the prognostic signature score status was better than without the nomogram or using the SAPS II at predicting hospital mortality.

Conclusion

The prognosis of SAE patients has nothing to do with intestinal and microbial infections. We developed a nomogram that predicts hospital mortality in patients with SAE according to clinical data. The nomogram exhibited excellent discrimination and calibration capacity, favoring its clinical utility.
Pan-Cancer Analysis Identified C1ORF112 as a Potential Biomarker for Multiple Tumor Types
Authors: Chen Jiaxuan , Mai Haoming , Chen Haitao , Zhou Bin , Hou Jinlin , Jiang De-Ke
Published: August 2021

C1ORF112 is an evolutionarily conserved gene across vertebrates. Over the last decade, studies have suggested that C1ORF112 may play a role in tumorigenesis. Using The Cancer Genome Atlas datasets, we explored the role of C1ORF112 across various tumor types in this study. In most tumor types, C1ORF112 expression was increased in tumor tissues compared to corresponding non-tumor tissues. In patients with certain tumor types, higher C1ORF112 expression was correlated with shorter overall survival, disease-free survival, and progression-free survival. Further analyses of C1ORF112 genetic alteration data showed that C1ORF112 amplification and mutations may have an impact on liver hepatocellular carcinoma and uterine corpus endometrial carcinoma prognosis. In cancers including lower grade glioma and adrenocortical carcinoma, C1ORF112 expression was linked to cancer-associated fibroblast infiltration. Gene Ontology analysis showed that C1ORF112 was co-expressed with genes involved in biological processes such as cell cycle and mitotic regulation. The protein interaction network demonstrated that C1ORF112 physically interacted with RAD51, DMC1, and FIGNL1, which have well characterized functions in DNA repair and cell cycle regulation. This pan-cancer study revealed the prognostic value and oncogenic role of C1ORF112 across multiple tumor types.
p53–GSDME Elevation: A Path for CDK7 Inhibition to Suppress Breast Cancer Cell Survival
Authors: Wang Yueyuan , Peng Jingyu , Mi Xuguang , Yang Ming
Published: August 2021

Higher cyclin-dependent kinase (CDK7) expression is a character of breast cancer and indicates poor prognosis. Inhibiting CDK7 exhibited effective cancer cell suppression which implies the potential of CDK7 inhibition to be a method for anti-cancer treatment. Our study aimed to explore a novel mechanism of CDK7 inhibition for suppressing breast cancer cell survival. Here, we proved inhibiting CDK7 repressed breast cancer cell proliferation and colony formation and increased the apoptotic cell rate, with p53 and GSDME protein level elevation. When p53 was suppressed in MCF-7 cells, the decline of GSDME expression and associated stronger proliferation and colony formation could be observed. Since downregulation of GSDME was of benefit to breast cancer cells, p53 inhibition blocked the elevation of GSDME induced by CDK7 inhibition and retrieved cells from the tumor suppressive effect of CDK7 inhibition. Therefore, CDK7 inhibition exerted a negative effect on breast cancer cell proliferation and colony formation in a p53–GSDME dependent manner. These results revealed the CDK7–p53–GSDME axis could be a pathway affecting breast cancer cell survival.
Exploring Amyloidogenicity of Peptides From Ribosomal S1 Protein to Develop Novel AMPs
Authors: Galzitskaya Oxana V.
Published: August 2021

Antimicrobial peptides (AMPs) and similar compounds are potential candidates for combating antibiotic-resistant bacteria. The hypothesis of directed co-aggregation of the target protein and an amyloidogenic peptide acting as an antimicrobial peptide was successfully tested for peptides synthesized on the basis of ribosomal S1 protein in the bacterial culture of T. thermophilus. Co-aggregation of the target protein and amyloidogenic peptide was also tested for the pathogenic ribosomal S1 protein from P. aeruginosa. Almost all peptides that we selected as AMPs, prone to aggregation and formation of fibrils, based on the amino acid sequence of ribosomal S1 protein from E. coli, T. thermophilus, P. aeruginosa, formed amyloid fibrils. We have demonstrated that amyloidogenic peptides are not only toxic to their target cells, but also some of them have antimicrobial activity. Controlling the aggregation of vital bacterial proteins can become one of the new directions of research and form the basis for the search and development of targeted antibacterial drugs.
Multi-Dimensional Enhanced Seizure Prediction Framework Based on Graph Convolutional Network
Authors: Chen Xin , Zheng Yuanjie , Dong Changxu , Song Sutao
Published: August 2021

In terms of seizure prediction, how to fully mine relational data information among multiple channels of epileptic EEG? This is a scientific research subject worthy of further exploration. Recently, we propose a multi-dimensional enhanced seizure prediction framework, which mainly includes information reconstruction space, graph state encoder, and space-time predictor. It takes multi-channel spatial relationship as breakthrough point. At the same time, it reconstructs data unit from frequency band level, updates graph coding representation, and explores space-time relationship. Through experiments on CHB-MIT dataset, sensitivity of the model reaches 98.61%, which proves effectiveness of the proposed model.
Broad and Long-Lasting Vision Improvements in Youth With Infantile Nystagmus After Home Training With a Perceptual Learning App
Authors: Huurneman Bianca , Goossens Jeroen
Published: August 2021

Current treatments for infantile nystagmus (IN), focused on dampening the oscillating eye movements, yield little to no improvement in visual functioning. It makes sense, however, to treat the visual impairments associated with IN with tailored sensory training. Recently, we developed such a training, targeting visual crowding as an important bottleneck in visual functioning with an eye-movement engaging letter discrimination task. This training improved visual performance of children with IN, but most children had not reached plateau performance after 10 supervised training sessions (3,500 trials). Here, we evaluate the effects of prolonged perceptual learning (14,000 trials) in 7-18-year-old children with IN and test the feasibility of tablet-based, at-home intervention. Results demonstrate that prolonged home-based perceptual training results in stable, long lasting visual acuity improvements at distance and near, with remarkably good transfer to reading and even stereopsis. Improvements on self-reported functional vision scores underline the clinical relevance of perceptual learning with e-health apps for individuals with IN.
Vagus Nerve Stimulation Therapy for the Treatment of Seizures in Refractory Postencephalitic Epilepsy: A Retrospective Study
Authors: Sun Yulin , Chen Jian , Fang Tie , Wan Lin , Shi Xiuyu , Wang Jing , Li Zhichao , Wang Jiaxin , Cui Zhiqiang , Xu Xin , Ling Zhipei , Zou Liping , Yang Guang
Published: August 2021

Background

Vagus nerve stimulation (VNS) has been demonstrated to be safe and effective for patients with refractory epilepsy, but there are few reports on the use of VNS for postencephalitic epilepsy (PEE). This retrospective study aimed to evaluate the efficacy of VNS for refractory PEE.

Methods

We retrospectively studied 20 patients with refractory PEE who underwent VNS between August 2017 and October 2019 in Chinese PLA General Hospital and Beijing Children’s Hospital. VNS efficacy was evaluated based on seizure reduction, effective rate (percentage of cases with seizure reduction ≥ 50%), McHugh classification, modified Early Childhood Epilepsy Severity Scale (E-Chess) score, and Grand Total EEG (GTE) score. The follow-up time points were 3, 6, and 12 months after VNS. Pre- and postoperative data were compared and analyzed.

Results

The median [interquartile range (IQR)] seizure reduction rates at 3, 6, and 12 months after VNS were 23.72% (0, 55%), 46.61% (0, 79.04%), and 67.99% (0, 93.78%), respectively. The effective rates were 30% at 3 months, 45% at 6 months, and 70% at 12 months. E-chess scores before the operation and at 3, 6, and 12 months after the operation were 10 (10, 10.75), 9 (9, 10), 9 (9, 9.75), and 9 (8.25, 9) (P < 0.05), respectively. GTE scores before surgery and at 12 months after the operation were 11 (9, 13) and 9 (7, 11) (P < 0.05), respectively. The mean intensity of VNS current was 1.76 ± 0.39 (range: 1.0–2.5) mA. No intraoperative complications or severe post-operative adverse effects were reported.

Conclusions

Our study shows that VNS can reduce the frequency and severity of seizure in patients with refractory PEE. VNS has a good application prospect in patients with refractory PEE.
TMS Motor Mapping Methodology and Reliability: A Structured Review
Authors: Sondergaard Rachel E. , Martino Davide , Kiss Zelma H. T. , Condliffe Elizabeth G.
Published: August 2021

Motor cortical representation can be probed non-invasively using a transcranial magnetic stimulation (TMS) technique known as motor mapping. The mapping technique can influence features of the maps because of several controllable elements. Here we review the literature on six key motor mapping parameters, as well as their influence on outcome measures and discuss factors impacting their selection. 132 of 1,587 distinct records were examined in detail and synthesized to form the basis of our review. A summary of mapping parameters, their impact on outcome measures and feasibility considerations are reported to support the design and interpretation of TMS mapping studies.
Application of Trio-Whole Exome Sequencing in Genetic Diagnosis and Therapy in Chinese Children With Epilepsy
Authors: Jiang Tiejia , Gao Jia , Jiang Lihua , Xu Lu , Zhao Congying , Su Xiaojun , Shen Yaping , Gu Weiyue , Kong Xiaohong , Yang Ying , Gao Feng
Published: August 2021

Epilepsy is one of the most common neurological disorders in pediatric patients with other underlying neurological defects. Identifying the underlying etiology is crucial for better management of the disorder. We performed trio-whole exome sequencing in 221 pediatric patients with epilepsy. Probands were divided into seizures with developmental delay/intellectual disability (DD/ID) and seizures without DD/ID groups. Pathogenic (P) or likely pathogenic (LP) variants were identified in 71/110 (64.5%) patients in the seizures with DD/ID group and 21/111 (18.9%) patients in the seizures without DD/ID group (P < 0.001). Eighty-seven distinct P/LP single nucleotide variants (SNVs)/insertion deletions (Indels) were detected, with 55.2% (48/87) of them being novel. All aneuploidy and P/LP copy number variants (CNVs) larger than 100 Kb were identifiable by both whole-exome sequencing and copy number variation sequencing (CNVseq) in 123 of individuals (41 pedigrees). Ten of P/LP CNVs in nine patients and one aneuploidy variant in one patient (Patient #56, #47, XXY) were identified by CNVseq. Herein, we identified seven genes (NCL, SEPHS2, PA2G4, SLC35G2, MYO1C, GPR158, and POU3F1) with de novo variants but unknown pathogenicity that were not previously associated with epilepsy. Potential effective treatment options were available for 32 patients with a P/LP variant, based on the molecular diagnosis. Genetic testing may help identify the molecular etiology of early onset epilepsy and DD/ID and further aid to choose the appropriate treatment strategy for patients.
Physical Exercise Modulates Brain Physiology Through a Network of Long- and Short-Range Cellular Interactions
Authors: Consorti Alan , Di Marco Irene , Sansevero Gabriele
Published: August 2021

In the last decades, the effects of sedentary lifestyles have emerged as a critical aspect of modern society. Interestingly, recent evidence demonstrated that physical exercise plays an important role not only in maintaining peripheral health but also in the regulation of central nervous system function. Many studies have shown that physical exercise promotes the release of molecules, involved in neuronal survival, differentiation, plasticity and neurogenesis, from several peripheral organs. Thus, aerobic exercise has emerged as an intriguing tool that, on one hand, could serve as a therapeutic protocol for diseases of the nervous system, and on the other hand, could help to unravel potential molecular targets for pharmacological approaches. In the present review, we will summarize the cellular interactions that mediate the effects of physical exercise on brain health, starting from the factors released in myocytes during muscle contraction to the cellular pathways that regulate higher cognitive functions, in both health and disease.
Anaerobic Solid-State Fermentation of Soybean Meal With Bacillus sp. to Improve Nutritional Quality
Authors: Yao Yanhui , Li Hongya , Li Jia , Zhu Baocheng , Gao Tongguo
Published: August 2021

The study evaluated the impact of fermentation with Bacillus sp. on the nutritional quality of soybean meal (SBM) and the changes of bacterial community structure during fermentation. High protease-producing strains were screened to degrade SBM macromolecular protein and anti-nutritional factors (ANFs). Unsterilized SBM then underwent an anaerobic solid-state fermentation method to evaluate the effects of fermentation. Results showed that for the nine high-producing protease strains that were screened, acid-soluble protein (ASP) contents in fermented SBM increased, with the highest value found to be 13.48%, which was fermented using strain N-11. N-11 was identified as Bacillus subtilis. N-11 fermentation reduced ANFs such as glycinin and β-conglycinin by 82.38 and 88.32%, respectively. During N-11 fermentation, the bacterial richness and diversity in SBM increased but not significantly. The high-yield protease strain B. subtilis N-11 selected in this experiment improved the nutritional quality of SBM through fermentation, and it can be used for industrial large-scale production.
Expression Patterns of Microenvironmental Factors and Tenascin-C at the Invasive Front of Stage II and III Colorectal Cancer: Novel Tumor Prognostic Markers
Authors: Hashimoto Mai , Uesugi Noriyuki , Osakabe Mitsumasa , Yanagawa Naoki , Otsuka Koki , Kajiwara Yoshiki , Ueno Hideki , Sasaki Akira , Sugai Tamotsu
Published: August 2021

Background

Biological markers expressed in cancer cells and the surrounding cancer-associated fibroblasts (CAF) can be used for prediction of patient prognosis in colorectal cancer (CRC). Here, we used immunohistochemical techniques to evaluate cancer cells’ expression of specific biomarkers that are closely associated with neoplastic progression.

Methods

Immunohistochemical markers included Ki-67, p53, β-catenin, MMP7, E-cadherin and HIF1-α. We also characterized microenvironmental markers expressed by CAF, including expression of α-smooth muscle actin, CD10, podoplanin, fibroblast specific protein 1, platelet derived growth factor β, fibroblast association protein, tenascin-C (TNC), ZEB1 and TWIST1. The study population consisted of 286 CRC patients with stage II and III disease. Stage II and III CRC were divided into a first and a second cohort (for validation). The CRCs were stratified using cluster analysis. To identify the utility of prognostic markers in stage II and III CRC, univariate and multivariate analyses were performed in both cohorts.

Results

Stage II and III CRCs were stratified into 3 subgroups. Specific subgroups were significantly correlated to disease-free survival using univariate and multivariate analyses in the first cohort. High expression of TNC was identified as a single prognostic marker in both cohorts by univariate and multivariate analyses.

Conclusions

We suggest that the presence of a specific subgroup defined by multiple markers can be used for prediction of CRC outcome in stages II and III. In addition, we showed that high expression of TNC was correlated with a poorer prognosis in stages II and III of CRC.
An Adversarial Deep-Learning-Based Model for Cervical Cancer CTV Segmentation With Multicenter Blinded Randomized Controlled Validation
Authors: Liu Zhikai , Chen Wanqi , Guan Hui , Zhen Hongnan , Shen Jing , Liu Xia , Liu An , Li Richard , Geng Jianhao , You Jing , Wang Weihu , Li Zhouyu , Zhang Yongfeng , Chen Yuanyuan , Du Junjie , Chen Qi , Chen Yu , Wang Shaobin , Zhang Fuquan , Qiu Jie
Published: August 2021

Purpose

To propose a novel deep-learning-based auto-segmentation model for CTV delineation in cervical cancer and to evaluate whether it can perform comparably well to manual delineation by a three-stage multicenter evaluation framework.

Methods

An adversarial deep-learning-based auto-segmentation model was trained and configured for cervical cancer CTV contouring using CT data from 237 patients. Then CT scans of additional 20 consecutive patients with locally advanced cervical cancer were collected to perform a three-stage multicenter randomized controlled evaluation involving nine oncologists from six medical centers. This evaluation system is a combination of objective performance metrics, radiation oncologist assessment, and finally the head-to-head Turing imitation test. Accuracy and effectiveness were evaluated step by step. The intra-observer consistency of each oncologist was also tested.

Results

In stage-1 evaluation, the mean DSC and the 95HD value of the proposed model were 0.88 and 3.46 mm, respectively. In stage-2, the oncologist grading evaluation showed the majority of AI contours were comparable to the GT contours. The average CTV scores for AI and GT were 2.68 vs. 2.71 in week 0 (P = .206), and 2.62 vs. 2.63 in week 2 (P = .552), with no significant statistical differences. In stage-3, the Turing imitation test showed that the percentage of AI contours, which were judged to be better than GT contours by ≥5 oncologists, was 60.0% in week 0 and 42.5% in week 2. Most oncologists demonstrated good consistency between the 2 weeks (P > 0.05).

Conclusions

The tested AI model was demonstrated to be accurate and comparable to the manual CTV segmentation in cervical cancer patients when assessed by our three-stage evaluation framework.
Hippocampus-Avoidance Whole-Brain Radiation Therapy Is Efficient in the Long-Term Preservation of Hippocampal Volume
Authors: Popp Ilinca , Rau Alexander , Kellner Elias , Reisert Marco , Fennell Jamina Tara , Rothe Thomas , Nieder Carsten , Urbach Horst , Egger Karl , Grosu Anca Ligia , Kaller Christoph P.
Published: August 2021

Background and Purpose

With improved life expectancy, preventing neurocognitive decline after cerebral radiotherapy is gaining more importance. Hippocampal damage has been considered the main culprit for cognitive deficits following conventional whole-brain radiation therapy (WBRT). Here, we aimed to determine to which extent hippocampus-avoidance WBRT (HA-WBRT) can prevent hippocampal atrophy compared to conventional WBRT.

Methods and Materials

Thirty-five HA-WBRT and 48 WBRT patients were retrospectively selected, comprising a total of 544 contrast-enhanced T1-weighted magnetic resonance imaging studies, longitudinally acquired within 24 months before and 48 months after radiotherapy. HA-WBRT patients were treated analogously to the ongoing HIPPORAD-trial (DRKS00004598) protocol with 30 Gy in 12 fractions and dose to 98% of the hippocampus ≤ 9 Gy and to 2% ≤ 17 Gy. WBRT was mainly performed with 35 Gy in 14 fractions or 30 Gy in 10 fractions. Anatomical images were segmented and the hippocampal volume was quantified using the Computational Anatomy Toolbox (CAT), including neuroradiological expert review of the segmentations.

Results

After statistically controlling for confounding variables such as age, gender, and total intracranial volume, hippocampal atrophy was found after both WBRT and HA-WBRT (p < 10−6). However, hippocampal decline across time following HA-WBRT was approximately three times lower than following conventional WBRT (p < 10−6), with an average atrophy of 3.1% versus 8.5% in the first 2 years after radiation therapy, respectively.

Conclusion

HA-WBRT is a therapeutic option for patients with multiple brain metastases, which can effectively and durably minimize hippocampal atrophy compared to conventional WBRT.
The Role of Gut Microbiota in Lung Cancer: From Carcinogenesis to Immunotherapy
Authors: Liu Xiangjun , Cheng Ye , Zang Dan , Zhang Min , Li Xiuhua , Liu Dan , Gao Bing , Zhou Huan , Sun Jinzhe , Han Xu , Lin Meixi , Chen Jun
Published: August 2021

The influence of microbiota on host health and disease has attracted adequate attention, and gut microbiota components and microbiota-derived metabolites affect host immune homeostasis locally and systematically. Some studies have found that gut dysbiosis, disturbance of the structure and function of the gut microbiome, disrupts pulmonary immune homeostasis, thus leading to increased disease susceptibility; the gut-lung axis is the primary cross-talk for this communication. Gut dysbiosis is involved in carcinogenesis and the progression of lung cancer through genotoxicity, systemic inflammation, and defective immunosurveillance. In addition, the gut microbiome harbors the potential to be a novel biomarker for predicting sensitivity and adverse reactions to immunotherapy in patients with lung cancer. Probiotics and fecal microbiota transplantation (FMT) can enhance the efficacy and depress the toxicity of immune checkpoint inhibitors by regulating the gut microbiota. Although current studies have found that gut microbiota closely participates in the development and immunotherapy of lung cancer, the mechanisms require further investigation. Therefore, this review aims to discuss the underlying mechanisms of gut microbiota influencing carcinogenesis and immunotherapy in lung cancer and to provide new strategies for governing gut microbiota to enhance the prevention and treatment of lung cancer.
TIMELESS Promotes Tumor Progression by Enhancing Macrophages Recruitment in Ovarian Cancer
Authors: Xing Xin , Gu Fei , Hua Lanyu , Cui Xiaoxiao , Li Dongxue , Wu Zhiyong , Zhang Rong
Published: August 2021

Objective

Ovarian cancer (OV) is the most fatal and frequent type of gynecological malignancy worldwide. TIMELESS (TIM), as a circadian clock gene, has been found to be highly expressed and predictive of poor prognosis in various cancers. However, the function of TIM in OV is not known. This study was designed to investigate the biological functions and underlying mechanisms of TIM during OV progression.

Methods

Cell viability assay, cell migration assay, immunohistochemistry staining, qPCR analyses, and tumor xenograft model were used to identify the functions of TIM in OV. Bioinformatics analyses, including GEPIA, cBioPortal, GeneMANIA, and TIMER, were used to analyze the gene expression, genetic alteration, and immune cell infiltration of TIM in OV.

Results

TIM is highly expressed in OV patients. TIM knockdown inhibited OV cell proliferation, migration, and invasion both in vitro and in vivo. Genetic alteration of TIM was identified in patients with OV. TIM co-expression network indicates that TIM had a wide effect on the immune cell infiltration and activation in OV. Further analysis and experimental verification revealed that TIM was positively correlated with macrophages infiltration in OV.

Conclusions

Our study unveiled a novel function of highly expressed TIM associated with immune cell especially macrophages infiltration in OV. TIM may serve as a potential prognostic biomarker and immunotherapy target for OV patients.
Methodological and Statistical Considerations for the National Children's Study
Authors: Hays Ron D. , Hubble David , Jenkins Frank , Fraser Alexa , Carew Beryl
Published: August 2021

The National Children's Study (NCS) statistics and item response theory group was tasked with promoting the quality of study measures and analysis. This paper provides an overview of six measurement and statistical considerations for the NCS: (1) Conceptual and Measurement Model; (2) Reliability; (3) Validity; (4) Measurement Invariance; (5) Interpretability of Scores; and (6) Burden of administration. The guidance was based primarily on recommendations of the International Society of Quality of Life Research.
Adverse Events During Supervised Exercise Interventions in Pediatric Oncology—A Nationwide Survey
Authors: Gauß Gabriele , Beller Ronja , Boos Joachim , Däggelmann Julia , Stalf Hannah , Wiskemann Joachim , Götte Miriam
Published: August 2021

Objectives: Exercise interventions during and after treatment for pediatric cancer are associated with beneficial physical, psychological, and social effects. However, valid data about adverse events (AEs) of such interventions have rarely been evaluated. This retrospective study evaluates AEs that occurred during supervised oncological exercise programs for pediatric cancer patients and survivors.

Methods: This Germany-wide study used a self-administered online survey focusing on general program characteristics and AEs retrospectively for 2019. The questionnaire included (a) basic data on the offered exercise program, (b) AEs with consequences (Grade 2–5) that occurred in 2019 during an exercise intervention, (c) number of Grade 1 AEs, (d) safety procedures as part of the exercise programs, and (e) possibility to give feedback and describe experience with AEs in free text.

Results: Out of 26 eligible exercise programs, response rate of program leaders was 92.3% (n = 24). Representatives working for Universities (n = 6), rehabilitation clinics (n = 3), acute cancer clinics (n = 12), and activity camps (n = 3) participated. In total, 35,110 exercise interventions with varying duration were recorded for 2019. Six AEs with consequences (Grade 2–3) occurred during exercise interventions after cancer treatment resulting in an incidence of 17 per 100,000 exercise interventions (0.017%). No life-threatening consequences or death were reported and no serious AE occurred during acute cancer treatment. Grade 1 AE occurred with a frequency of 983, corresponding to an incidence of 2,800 per 100,000 interventions (2.8%). Most frequent Grade 1 AE were muscle soreness, circulatory problems, and abdominal pain. The most frequent preventive safety procedures at the institutions were regular breaks, consultations with the medical treatment team, and material selection with low injury potential.

Conclusions: Supervised exercise interventions for pediatric cancer patients and survivors seem to be safe and AEs with consequences comparatively rare when compared to general childhood population data. Occurrence of grade 1 AEs was common, however, causality was probably not evident between AEs and the exercise intervention. Future research should standardize assessment of AEs in clinical practice and research, and prospectively register and evaluate AEs that occur in the context of exercise interventions in pediatric cancer patients and survivors.
Antibiotic Discontinuation 24 h After Neonatal Late-Onset Sepsis Work-Up—A Validated Decision Tree Model
Authors: Goldberg Ori , Sokolover Nir , Bromiker Ruben , Amitai Nofar , Chodick Gabriel , Scheuerman Oded , Ben-Zvi Haim , Klinger Gil
Published: August 2021

Objectives: Neonatal late-onset sepsis work-up is a frequent occurrence in every neonatal department. Blood cultures are the diagnostic gold standard, however, a negative culture prior to 48–72 h is often considered insufficient to exclude sepsis. We aimed to develop a decision tree which would enable exclusion of late-onset sepsis within 24 h using clinical and laboratory variables.

Study Design: Infants evaluated for late-onset sepsis during the years 2016–2019, without major malformations, in a tertiary neonatal center were eligible for inclusion. Blood cultures and clinical and laboratory data were extracted at 0 and 24 h after sepsis work-up. Infants with bacteriologically confirmed late-onset sepsis were compared to matched control infants. Univariate logistic regression identified potential risk factors. A decision tree based on Chi-square automatic interaction detection methodology was developed and validated.

Results: The study cohort was divided to a development cohort (105 patients) and a validation cohort (60 patients). At 24 h after initial evaluation, the best variables to identify sepsis were C-reactive protein > 0.75 mg/dl, neutrophil-to-lymphocyte ratio > 1.5 and sick-appearance at 24 h. Use of these 3 variables together with blood culture status at 24 h, enabled identification of all infants that eventually developed sepsis through the decision tree model. Our decision tree has an area under the receiver operating characteristic curve of 0.94 (95% CI: 0.90–0.98).

Conclusions: In non-sick appearing infants with a negative blood culture at 24 h and normal laboratory values, sepsis is highly unlikely and discontinuing antibiotics after 24 h is a viable option.
Pediatric Intensive Care Hybrid-Style Clinical Round During COVID-19 Pandemic: A Pilot Study
Authors: Temsah Mohamad-Hani , Alhboob Ali , Abouammoh Noura , Al-Eyadhy Ayman , Aljamaan Fadi , Alsohime Fahad , Alabdulhafid Majed , Ashry Ahmad , Bukhari Ahmad , ElTahir Omer , Jamal Amr , Halwani Rabih , Alhasan Khalid , Alherbish Adi , Temsah Reem , Al-Tawfiq Jaffar A. , Barry Mazin
Published: August 2021

Objectives: With the evolving COVID-19 pandemic and the emphasis on social distancing to decrease the spread of SARS-CoV-2 among healthcare workers (HCWs), our pediatric intensive care unit (PICU) piloted the integration of Zoom meetings into clinical rounds. We aimed to explore the feasibility of these hybrid virtual and physical clinical rounds for PICU patients.

Design: Mixed quantitative and qualitative deductive thematic content analysis of narrative responses.

Setting: PICU, single tertiary-care academic center.

Participants: Multidisciplinary PICU HCWs.

Interventions: Integration of Zoom meeting into clinical daily PICU rounds.

Measurements: For the quantitative part, we gathered the details of daily PICU hybrid rounds in terms of times, number of HCWs, and type of files shared through Zoom. For the qualitative part, open-ended questions were used.

Main Results: The physical round took statistically significantly less time (34.68 ± 14.842 min) as compared with the Zoom round (72.45 ± 22.59 min), p < 0.001. The most shared component in the virtual round was chest X-rays (93.5%). Thirty-one HCWs participated in focus group discussions and were included in the analysis. Some of the HCWs' perceived advantages of the hybrid rounds were enabling multidisciplinary discussions, fewer round interruptions, and practicality of virtual discussions. The perceived challenges were the difficulty of the bedside nurse attending the virtual round, decreased teaching opportunities for the trainees, and decreased interactions among the team members, especially if video streaming was not utilized.

Conclusions: Multidisciplinary hybrid virtual and physical clinical rounds in the PICU were perceived as feasible by HCWs. The virtual rounds decreased the physical contact between the HCWs, which could decrease the possibility of SARS-CoV-2 spread among the treating team. Still, several components of the hybrid round should be optimized to facilitate the virtual team-members' interactions and enhance the teaching experience.
Inconsistent Time-Dependent Effects of Tetramethylpyrazine on Primary Neurological Disorders and Psychiatric Comorbidities
Authors: Jiang Yue-Peng , Jin Yan , Bao Jie , Wang Song , Lai Wei-Dong , Wen Cheng-Ping , Xu Zheng-Hao , Yu Jie
Published: August 2021

The aim of this study was to investigate the time dependent effects of tetramethylpyrazine (TMP, main activity compound of Ligusticum chuanxiong Hort) on two neurological disorders and their neuropsychiatric comorbidities. 6 Hz corneal rapid kindling was used to induce epileptogenesis and the inflammatory pain was induced by intra-articular Complete Freund’s adjuvant (CFA) injection. The mechanical pain thresholds were measured using von Frey hair (D4, D11, D18, D25 after CFA first injection), and the vertical rearings of the mice was observed. To test the neuropsychiatric comorbidities, anxiety-like behaviors of mice were examined by open field and elevated plus maze tests. Two behavioral despair models, tail suspension test and forced swimming test were also used to evaluate the depressive like behaviors. The results showed that TMP administered from the initial day (D1-D35 in kindling model, D0-D14 and D0-D28 in CFA model) of modeling retarded both the developments of 6 Hz corneal rapid kindling epileptogenesis and the CFA induced inflammatory pain. In comparison, late periods administration of TMP (D21-D35 in kindling and D14-D28 in CFA model) showed no effect on the epileptogenesis and the generalized seizures (GS) of kindling, but alleviated maintenance of CFA induced inflammatory pain. Furthermore, we also found all TMP treatments from the initial day of modeling alleviated the co-morbid depressive and anxiety-like behaviors in both models; however, late periods treatments did not, either in kindling or the CFA induced inflammatory pain. BDNF/ERK signaling impairment was also tested by western blot, and the results showed that TMP administered from the initial day of modeling increased the hippocampal BDNF/ERK expression, whereas late period administration showed no effects. Overall, our findings reveal the inconsistent time dependent effects of Tetramethylpyrazine on neurological disorders and their relative neuropsychiatric comorbidities, and provide novel insight into the early application of TMP that might enhance hippocampal BDNF/ERK signaling to alleviate neuropsychiatric comorbidities in neurological diseases.
Association of Plasma Metabolic Biomarker Sphingosine-1-Phosphate With Cerebral Collateral Circulation in Acute Ischemic Stroke
Authors: Yu Fang , Feng Xianjing , Li Xi , Liu Zeyu , Liao Di , Luo Yunfang , Wei Minping , Huang Qin , Zhang Lin , Xia Jian
Published: August 2021

Background: The contribution of metabolic profile to the cerebral collateral circulation in acute ischemic stroke (AIS) has not been fully outlined. In this study, we conducted a metabolomic study to assess the relationship between the metabolic biomarkers and the collateral status of AIS.

Methods: A two-stage study was conducted from September 2019 to June 2021 in our hospital. There were 96 subjects including 66 patients with AIS and 30 healthy controls in the discovery stage and 80 subjects including 53 patients with AIS and 27 healthy controls in the validation stage. Collateral circulation was assessed by the Tan score based on computed tomographic angiography (CTA). Liquid chromatography-tandem mass spectrometry was used to identify differential metabolic markers. Then, an ELISA was employed to detect the plasma levels of sphingosine-1-phosphate (S1P).

Results:There were 114 differential metabolites between patients with AIS and control groups and 37 differential metabolites between good collateral circulation (GCC) and poor collateral circulation (PCC) groups. The pathway enrichment analysis revealed that arginine biosynthesis was the only statistically significant pathway between AIS and control groups and sphingolipid metabolism was the only statistically significant pathway between GCC and PCC groups. The differential metabolites sphinganine-1-phosphate (SA1P) and S1P belong to the sphingolipid metabolism. In the discovery stage, when the GCC group was compared with the PCC group, the receiver operating characteristic (ROC) analysis showed that plasma SA1P relative levels demonstrated an area under the curve (AUC) of 0.719 (95% CI: 0.582–0.834), and S1P levels demonstrated an AUC of 0.701 (95% CI: 0.567–0.819). In addition, both plasma SA1P and S1P relative levels showed significant negative correlations with the 90-day modified Rankin Scale (mRS) score. In the validation sample, higher plasma S1P levels were independent predictors of GCC (p = 0.014), and plasma S1P levels demonstrated an AUC of 0.738 (95% CI: 0.599–0.849) to differentiate patients with GCC from patients with PCC. In addition, plasma S1P levels also showed significant negative correlations with the 90-day mRS score.

Conclusion: We first illustrated the association between plasma metabolic profiles and cerebral collateral circulation in patients with AIS. Plasma S1P levels might be a potential diagnostic biomarker for predicting collateral circulation status in patients with AIS.
Effect of Environmental Stress on the Nutrient Stoichiometry of the Clonal Plant Phragmites australis in Inland Riparian Wetlands of Northwest China
Authors: Zhou Yi , Jiao Liang , Qin Huijun , Li Fang
Published: August 2021

Clonal plants play an important role in determining ecosystem properties such as community stability, species diversity and nutrient cycling. However, relatively little information is available about the stoichiometric characteristics of clonal plants and their drivers in inland riparian wetlands under strong environmental stress. In this manuscript, we studied the clonal plantPhragmites australisin an inland riparian wetland of Northwest China and compared its nutrient distribution and stoichiometry trade-offs as well as its responses to soil environmental factors in three different environments, namely, a wetland, a salt marsh, and a desert. We found that (1)P. australiscould adapt to heterogeneous environments by changing its nutrient allocation strategies, as evidenced by the significant decrease in N and P concentrations, and significant increase in whole-plant C:P and N:P ratios from the wetland to the desert habitats. (2)P. australisadapted to stressful environments by changing its nutrient allocation patterns among different modules, showing a greater tendency to invest N and P in underground modules (rhizomes and roots) and an increase in the utilization efficiency of N and P in the leaves, and stems as environmental stress increased. (3) The C-N, C-P, and N:P-C in the whole plant and in each module showed significant anisotropic growth relationships in the three habitats (P< 0.05). (4) Soil water, pH and salt were the main factors limiting nutrient stoichiometry. The results of this study clarified the ecological adaptation mechanism of the clonal plantP. australisto heterogeneous environments and provided targeted protection strategies for inland riparian wetlands in Northwest China.
Transcriptome Analysis Reveals the Important Role of WRKY28 in Fusarium oxysporum Resistance
Authors: Diao Jian , Wang Jiaqi , Zhang Ping , Hao Xin , Wang Yang , Liang Liwei , Zhang Yue , Ma Wei , Ma Ling
Published: August 2021

Root rot of Populus davidiana × P. alba var. pyramidalis Louche (Pdpap) is caused by Fusarium oxysporum. We used RNA sequencing to study the molecular mechanisms and response pattern of Pdpap infected by F. oxysporum CFCC86068. We cloned the PdpapWRKY28 transcription factor gene and transformed the recombinant vector pBI121-PdpapWRKY28 into Pdpap. The resistance function of PdpapWRKY28 was verified using physiological and biochemical methods. By means of RNA sequencing, we detected 1,403 differentially expressed genes (DEGs) that are common in the different treatments by F. oxysporum. Furthermore, we found that overexpression of the PdpapWRKY28 gene may significantly improve the resistance of Pdpap plants to F. oxysporum. Our research reveals a key role for PdpapWRKY28 in the resistance response of Pdpap to F. oxysporum. Additionally, our results provide a theoretical basis for in-depth research on resistance breeding to combat root rot.
Pomegranate Fruit Growth and Skin Characteristics in Hot and Dry Climate
Authors: Joshi Mukul , Schmilovitch Ze’ev , Ginzberg Idit
Published: August 2021

Pomegranate (Punica granatumL.) fruit is well known for its health-beneficial metabolites. The pomegranate peel consists of an inner thick spongy white tissue, and an outer smooth skin layer that accumulates anthocyanins in red cultivars when ripe. The skin is made up of epidermis cells covered by a cuticle, the latter being the first target of cracking and russeting. The present study focuses on the effect of Israel’s hot and dry climate on pomegranate growth, to elucidate the derived effects on fruit skin characteristics and its putative resistance to the building pressure from fruit expansion. Experiments were conducted for four years, in four orchards located in different regions of the country, each with a different typical microclimate. Fruit-growth parameters were followed using remote-sensing tools, microscopic study, and mineral analysis of the skin, followed by determination of the peel’s elastic modulus. Fruit expanded in two phases: a short rapid phase followed by a gradual phase with a sigmoidal growth-rate pattern. Extreme hot and dry climate during the period of maximal growth rate was associated with restricted growth and a high proportion of small-size fruit. Anatomical study indicated that the skin of mature pomegranate fruit is made up of epidermal cells that are relatively flat and spaced apart, and is expected to be less durable against internal pressure. In contrast, skin of early immature fruit has two layers of dense and rounded epidermis, and is expected to be more resistant to cracking. Tensile strength studies confirmed this trend—skin of mature fruit had a lower elastic modulus than young fruit. However, restrained growth due to extreme environmental cues may result in better resistance of the mature pomegranate fruit to cracking, and in better skin quality and appearance, albeit small fruits. On the other hand, temperate climate at the beginning of the growth period, which allows high growth rate and high daily shrinkage, leads to pomegranate skin disorders.
Perceived Decrease in Workplace Security Since the Beginning of the COVID-19 Pandemic: The Importance of Management Styles and Work-Related Attitudes
Authors: Wojtkowska Anna , Tyburski Ernest , Skalacka Katarzyna , Gasiorowska Agata
Published: August 2021

The coronavirus disease 2019 (COVID-19) pandemic has reduced the sense of security of people in everyday life. The efforts of managers in the workplace to minimize the health risks and economic damage, however, can provide the employees with a greater sense of security. The aim of this study was to identify the types of workplace responses to the pandemic outbreak with respect to the characteristics of employees and their employers accomplishing the differences in subjective sense of workplace security before the pandemic and during the outbreak. Three hundred and thirty-seven Polish employees completed an online survey during the first 2 weeks of the COVID-19 pandemic in March 2020. Using the cluster analysis, we identified four subgroups of employees differing in their sense of workplace security, work-related psychological factors, and perceived management styles of their supervisors. Employees led by developers and executive managers sustained a high sense of work security and positive attitude to work, while those led by compromisers and deserter managers suffered from the highest drop of subjective security. In this study, we proposed how employees can be protected from overreactions and unnecessary panic in a time of global crisis by virtue of the psychological competences of their supervisors and employers.