bluuebunny/crossref_metadata_2025 huggingface dataset:
The GSK-3 Inhibitor CT99021 Enhances the Acquisition of Spatial Learning and the Accuracy of Spatial Memory
Authors: Lee Yeseul , Bortolotto Zuner A. , Bradley Clarrisa A. , Sanderson Thomas M. , Zhuo Min , Kaang Bong-Kiun , Collingridge Graham L.
Published: January 2022

Glycogen synthase kinase 3 (GSK-3) is a Ser/Thr protein kinase that regulates many cellular processes, including synaptic plasticity. Previously, we reported that inhibition of GSK-3 prevents the induction of one of the major forms of synaptic plasticity, N-methyl-D-aspartate receptor (NMDAR)-dependent long-term depression (LTD), in hippocampal slices. In the present study, we have investigated the effects of inhibiting GSK-3 on learning and memory in healthy naïve animals. Systemic administration of a highly selective GSK-3 inhibitor, CT99021, reversibly blocked NMDAR-dependent LTD in the CA1 region of the hippocampus in anesthetized adult mice. In behavioral tasks, CT99021 had no effect on locomotor activity, anxiety, hippocampus-dependent contextual fear memory, and hippocampus-dependent reversal learning. However, CT99021 facilitated the rate of learning in the Morris water maze (MWM) and T-maze and enhanced the accuracy of long-term spatial memory in the MWM. These findings suggest that GSK-3 regulates the accuracy of spatial memory acquisition and recall.
Impact of Body Composition on Prognosis and Dose-Limiting Toxicities on Metastatic Colorectal Cancer
Authors: da Silva Dias David , Machado Mafalda , Trabulo Carolina , Gosálbez Beatriz , Ravasco Paula
Published: January 2022

Sarcopenia is a progressive skeletal muscle disease, often present in oncological patients, that is associated with multiple adverse events such as worse prognosis, physical performance, and quality of life. Body composition evaluation by CT cross-section at the L3 vertebrae region appears to be a precise method to quantify skeletal muscle. The optimal cut-off for the definition of sarcopenia is not yet established, therefore the incidence of sarcopenia varies according to different studies. The main goal was to evaluate the presence of sarcopenia in patients with metastatic colorectal cancer (mCRC) and its impact on overall survival (OS) and dose-limiting toxicities (DLT). A retrospective cohort study of 178 patients with mCRC under first-line chemotherapy (ChT) in association with target therapy, in two hospital units, between January 2015 and December 2018. Skeletal mass area (SMA) was quantified with the NIH ImageJ software in CT cross-sectional images at the L3 vertebrae region. Statistical analysis was performed with IBM SPSS v25 softwarehttps://www.ibm.com/analytics/spss-statistics-software. The median age was 62 (SD ± 11) years old, 65% were men and 62.9% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0. The cut-off value was established based on ROC analysis, with sarcopenia defined as SMI < 49.12 cm2/m2 for men and < 35.85 cm2/m2 for women. Despite the mean body mass index (BMI) of 25.71 (± 4.71) kg/m2, half of the patients presented sarcopenia. In a multivariate analysis using a Cox regression model, an association was observed between OS and higher ECOG PS (p = 0.014; HR 5.46, CI 95% [1.42–21.10]), neutrophil-to-lymphocyte ratio (NLR) >2.80 (p = 0.038; HR 2.20, CI 95% [1,05–4.62]), and sarcopenia (p = 0.01; HR 4.73, CI 95% [1.85–12.09]). Additionally, in a logistic regression model, age (p = 0.014; OR 1.09, IC 95% [1.02–1.16]) and sarcopenia (p= 0.030, OR 4.13, IC 95% [1.15-14.8]) were associated with higher incidence of DLT. The CT evaluation of the body composition at the L3 region allows for the quantification of sarcopenia, providing prognostic information and predictive value of DLT in patients with mCRC, although the establishment of optimal cut-off values are required for implementation in clinical practice. A multimodal strategy to delay muscle waste should be considered in these patients.
Multi-Dimensional Dataset of Open Data and Satellite Images for Characterization of Food Security and Nutrition
Authors: Restrepo David S. , Pérez Luis E. , López Diego M. , Vargas-Cañas Rubiel , Osorio-Valencia Juan Sebastian
Published: January 2022

Background

Nutrition is one of the main factors affecting the development and quality of life of a person. From a public health perspective, food security is an essential social determinant for promoting healthy nutrition. Food security embraces four dimensions: physical availability of food, economic and physical access to food, food utilization, and the sustainability of the dimensions above. Integrally addressing the four dimensions is vital. Surprisingly most of the works focused on a single dimension of food security: the physical availability of food.

Objective

The paper proposes a multi-dimensional dataset of open data and satellite images to characterize food security in the department of Cauca, Colombia.

Methods

The food security dataset integrates multiple open data sources; therefore, the Cross-Industry Standard Process for Data Mining methodology was used to guide the construction of the dataset. It includes sources such as population and agricultural census, nutrition surveys, and satellite images.

Results

An open multidimensional dataset for the Department of Cauca with 926 attributes and 9 rows (each row representing a Municipality) from multiple sources in Colombia, is configured. Then, machine learning models were used to characterize food security and nutrition in the Cauca Department. As a result, The Food security index calculated for Cauca using a linear regression model (Mean Absolute Error of 0.391) is 57.444 in a range between 0 and 100, with 100 the best score. Also, an approach for extracting four features (Agriculture, Habitation, Road, Water) of satellite images were tested with the ResNet50 model trained from scratch, having the best performance with a macro-accuracy, macro-precision, macro-recall, and macro-F1-score of 91.7, 86.2, 66.91, and 74.92%, respectively.

Conclusion

It shows how the CRISP-DM methodology can be used to create an open public health data repository. Furthermore, this methodology could be generalized to other types of problems requiring the creation of a dataset. In addition, the use of satellite images presents an alternative for places where data collection is challenging. The model and methodology proposed based on open data become a low-cost and effective solution that could be used by decision-makers, especially in developing countries, to support food security planning.
Clinical Benefits From Administering Probiotics to Mechanical Ventilated Patients in Intensive Care Unit: A PRISMA-Guided Meta-Analysis
Authors: Song Hongzhuan , Hu Wenqing , Zhou Xiujie , Tao Jiaping , Zhang Siyi , Su Xuhong , Wu Wenjun
Published: January 2022

Background

The use of probiotics has been considered as a new intervention for ventilator-associated pneumonia (VAP) prevention in the intensive care unit (ICU). The aim of this meta-analysis was to evaluate the effect of probiotics on mechanical-ventilated patients in ICU.

Methods

PubMed, Embase, Scopus, and the Cochrane Library were searched for relevant randomized controlled trials (RCTs) from their respective inception through October 10, 2021. All studies meeting the inclusion criteria were selected to evaluate the effect of probiotics on patients receiving mechanical ventilation in ICU.

Results

A total of 15 studies involving 4,693 participants met our inclusion criterion and were included in this meta-analysis. The incidence of VAP in the probiotic group was significantly lower (odds ratio [OR] 0.58, 95% CI 0.41 to 0.81; p = 0.002; I2 = 71%). However, a publication bias may be present as the test of asymmetry was significant (p = 0.007). The probiotic administration was associated with a significant reduction in the duration of mechanical ventilation (mean difference [MD] −1.57, 95% CI −3.12 to −0.03; p = 0.05; inconsistency [I]2 = 80%), length of ICU stay (MD −1.87, 95% CI −3.45 to −0.28; p = 0.02; I2 = 76%), and incidence of bacterial colonization (OR 0.59, 95% CI 0.45 to 0.78; p = 0.0001; I2 = 34%). Moreover, no statistically significant differences were observed regarding the incidence of diarrhea (OR 0.90, 95% CI 0.65 to 1.25; p = 0.54; I2 = 12%) and mortality (OR 0.91, 95% CI 0.80 to 1.05; p = 0.19; I2 = 0%) between probiotics group and control group.

Conclusion

Our meta-analysis shows that probiotics are associated with a reduction in VAP, as well as the duration of mechanical ventilation, ICU length of stay, and bacterial colonization, but no significant effects on ICU mortality and occurrence of diarrhea. However, in consideration of the significant heterogeneity and publication bias, our findings need to be further validated.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifier: CRD42020150770.
Enrichment in Different Health Components of Barley Flour Using Twin-Screw Extrusion Technology to Support Nutritionally Balanced Diets
Authors: Punia Bangar Sneh , Singh Sandhu Kawaljit , Trif Monica , Rusu Alexandru , Pop Ioana Delia , Kumar Manoj
Published: January 2022

Due to its good dietary role, barley has attracted a growing amount of interest for the manufacture of functional foods in recent years. In barley, a number of bioactive components, including as phenolic compounds, have been discovered, and barley extrudates could be used to formulate various processed foods, including ready-to-eat cereals, baby, and pet foods and support nutritionally balanced diets. This study was conducted to investigate the effect of extrusion processing on resistant starch (RS), glycemic index (GI), and antioxidant compounds of barley flour. The L* and ΔE values of barley flours decreased significantly (p < 0.05) after extrusion is done at 150 and 180°C. The a* and b* values, however, increased after extrusion. Extrusion increased antioxidant activity (AOA), metal chelating activity (MCA), and ABTS+ scavenging activity, whereas total phenolic content (TPC) and total flavonoids content (TFC) decreased. Barley extrudates at 150 and 180°C showed decreased TPC by 16.4–34.2% and 23.4–38.1%. Moreover, improved RS and reduced GI values were recorded for barley extrudates as compared to barley non-extrudates. Therefore, extrusion of barley could be an alternative to produce pregelatinized barley flour with improved RS low GI values and improved antioxidant potential.
Development and Validation of a CT-Based Radiomics Nomogram for Predicting Postoperative Progression-Free Survival in Stage I–III Renal Cell Carcinoma
Authors: Zhang Haijie , Yin Fu , Chen Menglin , Yang Liyang , Qi Anqi , Cui Weiwei , Yang Shanshan , Wen Ge
Published: January 2022

Background

Many patients experience recurrence of renal cell carcinoma (RCC) after radical and partial nephrectomy. Radiomics nomogram is a newly used noninvasive tool that could predict tumor phenotypes.

Objective

To investigate Radiomics Features (RFs) associated with progression-free survival (PFS) of RCC, assessing its incremental value over clinical factors, and to develop a visual nomogram in order to provide reference for individualized treatment.

Methods

The RFs and clinicopathological data of 175 patients (125 in the training set and 50 in the validation set) with clear cell RCC (ccRCC) were retrospectively analyzed. In the training set, RFs were extracted from multiphase enhanced CT tumor volume and selected using the stability LASSO feature selection algorithm. A radiomics nomogram final model was developed that incorporated the RFs weighted sum and selected clinical predictors based on the multivariate Cox proportional hazard regression. The performances of a clinical variables-only model, RFs-only model, and the final model were compared by receiver operator characteristic (ROC) analysis and DeLong test. Nomogram performance was determined and validated with respect to its discrimination, calibration, reclassification, and clinical usefulness.

Results

The radiomics nomogram included age, clinical stage, KPS score, and RFs weighted sum, which consisted of 6 selected RFs. The final model showed good discrimination, with a C-index of 0.836 and 0.706 in training and validation, and good calibration. In the training set, the C-index of the final model was significantly larger than the clinical-only model (DeLong test, p = 0.008). From the clinical variables-only model to the final model, the reclassification of net reclassification improvement was 18.03%, and the integrated discrimination improvement was 19.08%. Decision curve analysis demonstrated the clinical usefulness of the radiomics nomogram.

Conclusion

The CT-based RF is an improvement factor for clinical variables-only model. The radiomics nomogram provides individualized risk assessment of postoperative PFS for patients with RCC.
A Novel IGLC2 Gene Linked With Prognosis of Triple-Negative Breast Cancer
Authors: Chang Yu-Tien , Tsai Wen-Chiuan , Lin Wei-Zhi , Wu Chia-Chao , Yu Jyh-Cherng , Tseng Vincent S. , Liao Guo-Shiou , Hu Je-Ming , Hsu Huan-Ming , Chang Yu-Jia , Lin Meng-Chiung , Chu Chi-Ming , Yang Chien-Yi
Published: January 2022

Background

Immunoglobulin-related genes are associated with the favorable prognosis of triple-negative breast cancer (TNBC) patients. We aimed to analyze the function and prognostic value of immunoglobulin lambda constant 2 (IGLC2) in TNBC patients.

Methods

We knocked down the gene expression of IGLC2 (IGLC2-KD) in MDA-MB-231 cells to evaluate the proliferation, migration, and invasion of tumors via 3-(4,5-Dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, wound healing, and transwell cell migration assay respectively. Relapse-free survival (RFS) and distant metastasis-free survival (DMFS) analyses were conducted using the KM plotter online tool. The GSE76275 data set was used to analyze the association of IGLC2 and clinical characteristics. A pathway enrichment analysis was conducted using the next-generation sequencing data of wild-type and IGLC2-KD MDA-MB-231 cells.

Results

The low gene expression of IGLC2 was related to unfavorable RFS, DMFS. The high expression of IGLC2 was exhibited in the basal-like immune-activated (BLIA) TNBC molecular subtype, which was immune-activated and showed excellent response to immune therapy. IGLC2 was positively correlated with programmed death-ligand 1 (PD-L1) as shown by Spearman correlation (r = 0.25, p < 0.0001). IGLC2 had a strong prognostic effect on lymph node-negative TNBC (RFS range: 0.31, q value= 8.2e-05; DMFS = 0.16, q value = 8.2e-05) but had no significance on lymph node-positive ones. The shRNA-mediated silencing of IGLC2 increased the proliferation, migration, and invasion of MDA-MB-231 cells. The results of pathway enrichment analysis showed that IGLC2 is related to the PI3K-Akt signaling pathway, MAPK signaling pathway, and extracellular matrix–receptor interaction. We confirmed that MDA-MB-231 tumor cells expressed IGLC2, subverting the traditional finding of generation by immune cells.

Conclusions

IGLC2 linked with the proliferation, migration, and invasion of MDA-MB-231 cells. A high expression of IGLC2 was related to favorable prognosis for TNBC patients. IGLC2 may serve as a biomarker for the identification of TNBC patients who can benefit the most from immune checkpoint blockade treatment.
Synergistic Anti-Tumor Effect of Combining Selective CDK7 and BRD4 Inhibition in Neuroblastoma
Authors: Gao Yang , Volegova Marina , Nasholm Nicole , Das Sanjukta , Kwiatkowski Nicholas , Abraham Brian J. , Zhang Tinghu , Gray Nathanael S. , Gustafson Clay , Krajewska Malgorzata , George Rani E.
Published: January 2022

Purpose

Cyclin-dependent kinases (CDKs) that have critical roles in RNA polymerase II (Pol II)-mediated gene transcription are emerging as therapeutic targets in cancer. We have previously shown that THZ1, a covalent inhibitor of CDKs 7/12/13, leads to cytotoxicity in MYCN-amplified neuroblastoma through the downregulation of super-enhancer-associated transcriptional upregulation. Here we determined the effects of YKL-5-124, a novel covalent inhibitor with greater selectivity for CDK7 in neuroblastoma cells.

Experimental Design

We tested YKL-5-124 in MYCN-amplified and nonamplified neuroblastoma cells individually and in combination with other inhibitors in cell line and animal models. Cell viability, target validation, effects on cell cycle and transcription were analyzed.

Results

CDK7 inhibition with YKL-5-124 did not lead to significant cell death, but resulted in aberrant cell cycle progression especially in MYCN-amplified cells. Unlike THZ1, YKL-5-124 had minimal effects on Pol II C-terminal domain phosphorylation, but significantly inhibited that of the CDK1 and CDK2 cell cycle kinases. Combining YKL-5-124 with the BRD4 inhibitor JQ1 resulted in synergistic cytotoxicity. A distinct MYCN-gene expression signature associated with resistance to BRD4 inhibition was suppressed with the combination. The synergy between YKL-5-124 and JQ1 translated into significant tumor regression in cell line and patient-derived xenograft mouse models of neuroblastoma.

Conclusions

The combination of CDK7 and BRD4 inhibition provides a therapeutic option for neuroblastoma and suggests that the addition of YKL-5-124 could improve the therapeutic efficacy of JQ1 and delay resistance to BRD4 inhibition.
A Retrospective Analysis of a Cohort of Patients Treated With Immune Checkpoint Blockade in Recurrent/Metastatic Head and Neck Cancer
Authors: Bila Michel , Van Dessel Jeroen , Smeets Maximiliaan , Vander Poorten Vincent , Nuyts Sandra , Meulemans Jeroen , Clement Paul M.
Published: January 2022

Objective

The treatment approach of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) has long been similar for all patients. Any difference in treatment strategy was only based on existing comorbidities and on preferences of the patient and the treating oncologist. The recent advance obtained with immune therapy and more specifically immune checkpoint blockade (ICB) has been a true game changer. Today, patients and physicians have a choice to omit chemotherapy. In a small subset of patients, ICB induces a very durable disease control. The subgroup of patients in which ICB without chemotherapy would be the preferential approach is still ill-defined. Yet, this evolution marks a major step towards a more personalized medicine in R/M HNSCC.

Materials and Methods

In this paper, we present a retrospective cohort study of a patient population that was treated with ICB in a single center and we analyze potential factors that are associated with outcome and may help to select patients for treatment with ICB.

Results

137 consecutively treated patients were identified. Male gender and metastatic disease appeared to be associated with improved overall survival (OS). There was no correlation observed with age, number of previous treatment lines or immune target.

Conclusion

Along with PD-L1 status defined by Combined Positive Score (CPS), clinical parameters such as site of recurrence and gender may help to define the optimal treatment strategy in R/M HNSCC.
Risk Stratification for the Rate and Location of Residual Bladder Tumor for the Decision of Re-Transurethral Resection of Bladder Tumor
Authors: Fan Junjie , Zhang Xing , Fan Jinhai , Li Lei , He Dalin , Wu Kaijie
Published: January 2022

Introduction

To assess the rate and location of residual tumor in re-transurethral resection of bladder tumor (re-TURBT) and develop a risk stratification tool to assist clinicians in making treatment decisions.

Patients and Methods

The data of 144 patients with high-risk bladder cancer who received re-TURBT were retrospectively reviewed. The rate and location of residual tumors was recorded. Logistic regression was performed to explore risk factors for residual tumors, and a risk classification tool was developed.

Results

Among the 144 patients, the rates of residual tumor and tumor location at the base of the primary tumor were 22.2% and 10.4%, respectively. Non-urothelial carcinoma subspecialist, piecemeal resection and the absence of detrusor muscle in the first specimen were defined as risk factors. Patients were categorized into low-, intermediate-, and high-risk groups according to the number of risk factors. The rate of residual tumor in the high-risk group was significantly higher than that in the low- and intermediate-risk groups (50% vs. 7.8%, P=0.001; 50% vs. 18.6%, P=0.002). Moreover, high-risk patients benefitted more from a second resection at the base of the primary tumor due to the high rate of residual tumor located at this site than low- and intermediate-risk patients (23.5% vs. 2.0%, P=0.002; 23.5% vs. 10.2%, P=0.083).

Conclusions

Risk stratification based on the subspecialist category, operative method, and presence or absence of detrusor muscle in the first specimen could help identify patients who benefit from re-TURBT and second resection the base of the primary tumor.
Comparison of Laboratory Methods for the Clinical Follow Up of Checkpoint Blockade Therapies in Leukemia: Current Status and Challenges Ahead
Authors: Aru Basak , Soltani Mojdeh , Pehlivanoglu Cemil , Gürlü Ege , Ganjalikhani-Hakemi Mazdak , Yanikkaya Demirel Gülderen
Published: January 2022

The development of immune checkpoint inhibitors, the monoclonal antibodies that modulate the interaction between immune checkpoint molecules or their ligands on the immune cells or tumor tissue has revolutionized cancer treatment. While there are various studies proving their efficacy in hematological malignancies, there is also a body of accumulating evidence indicating that immune checkpoint inhibitors’ clinical benefits are limited in such diseases. In addition, due to their regulatory nature that balances the immune responses, blockade of immune checkpoints may lead to toxic side effects and autoimmune responses, and even primary or acquired resistance mechanisms may restrict their success. Thus, the need for laboratory biomarkers to identify and monitor patient populations who are more likely respond to this type of therapy and the management of side effects seem critical. However, guidelines regarding the use of immune checkpoint inhibitors in hematological cancers and during follow-up are limited while there is no consensus on the laboratory parameters to be investigated for safety and efficacy of the treatment. This review aims to provide an insight into recent information on predictive and prognostic value of biomarkers and laboratory tests for the clinical follow up of hematological malignancies, with an emphasis on leukemia.
Downgrade BI-RADS 4A Patients Using Nomogram Based on Breast Magnetic Resonance Imaging, Ultrasound, and Mammography
Authors: Xie Yamie , Zhu Ying , Chai Weimin , Zong Shaoyun , Xu Shangyan , Zhan Weiwei , Zhang Xiaoxiao
Published: January 2022

Objectives

To downgrade BI-RADS 4A patients by constructing a nomogram using R software.

Materials and Methods

A total of 1,717 patients were retrospectively analyzed who underwent preoperative ultrasound, mammography, and magnetic resonance examinations in our hospital from August 2019 to September 2020, and a total of 458 patients of category BI-RADS 4A (mean age, 47 years; range 18–84 years; all women) were included. Multivariable logistic regression was used to screen out the independent influencing parameters that affect the benign and malignant tumors, and the nomogram was constructed by R language to downgrade BI-RADS 4A patients to eligible category.

Results

Of 458 BI-RADS 4A patients, 273 (59.6%) were degraded to category 3. The malignancy rate of these 273 lesions is 1.5% (4/273) (<2%), and the sensitivity reduced to 99.6%, the specificity increased from 4.41% to 45.3%, and the accuracy increased from 63.4% to 78.8%.

Conclusion

By constructing a nomogram, some patients can be downgraded to avoid unnecessary biopsy.
The Road to CAR T-Cell Therapies for Pediatric CNS Tumors: Obstacles and New Avenues
Authors: Burns Ian , Gwynne William D. , Suk Yujin , Custers Stefan , Chaudhry Iqra , Venugopal Chitra , Singh Sheila K.
Published: January 2022

Pediatric central nervous system (CNS) tumors are the most common solid tumors diagnosed in children and are the leading cause of pediatric cancer-related death. Those who do survive are faced with the long-term adverse effects of the current standard of care treatments of chemotherapy, radiation, and surgery. There is a pressing need for novel therapeutic strategies to treat pediatric CNS tumors more effectively while reducing toxicity – one of these novel modalities is chimeric antigen receptor (CAR) T-cell therapy. Currently approved for use in several hematological malignancies, there are promising pre-clinical and early clinical data that suggest CAR-T cells could transform the treatment of pediatric CNS tumors. There are, however, several challenges that must be overcome to develop safe and effective CAR T-cell therapies for CNS tumors. Herein, we detail these challenges, focusing on those unique to pediatric patients including antigen selection, tumor immunogenicity and toxicity. We also discuss our perspective on future avenues for CAR T-cell therapies and potential combinatorial treatment approaches.
Inhibition of Nociception in a Preclinical Episodic Migraine Model by Dietary Supplementation of Grape Seed Extract Involves Activation of Endocannabinoid Receptors
Authors: Woodman Sara E. , Antonopoulos Sophia R. , Durham Paul L.
Published: January 2022

Migraine is associated with peripheral and central sensitization of the trigeminal system and dysfunction of descending pain modulation pathways. Recently, dietary inclusion of grape seed extract (GSE) was shown to inhibit mechanical nociception in a preclinical model of chronic temporomandibular joint disorder, a condition often comorbid with migraine, with the antinociceptive effect mediated, in part, by activation of 5-HT3/7 and GABAB receptors. This study further investigated the mechanisms by which GSE inhibits mechanical nociception in a preclinical model of episodic migraine. Hyperalgesic priming of female and male Sprague Dawley rats was induced by three consecutive daily two-hour episodes of restraint stress. Seven days after the final restraint stress, rats were exposed to pungent odors from an oil extract that contains the compound umbellulone, which stimulates CGRP release and induces migraine-like pain. Some animals received dietary supplementation of GSE in their drinking water beginning one week prior to restraint stress. Changes in mechanical sensitivity in the orofacial region and hindpaw were determined using von Frey filaments. To investigate the role of the endocannabinoid receptors in the effect of GSE, some animals were injected intracisternally with the CB1 antagonist AM 251 or the CB2 antagonist AM 630 prior to odor inhalation. Changes in CGRP expression in the spinal trigeminal nucleus (STN) in response to stress, odor and GSE supplementation were studied using immunohistochemistry. Exposure of stress-primed animals to the odor caused a significant increase in the average number of withdrawal responses to mechanical stimulation in both the orofacial region and hindpaw, and the effect was significantly suppressed by daily supplementation with GSE. The anti-nociceptive effect of GSE was inhibited by intracisternal administration of antagonists of CB1 and CB2 receptors. GSE supplementation inhibited odor-mediated stimulation of CGRP expression in the STN in sensitized animals. These results demonstrate that GSE supplementation inhibits trigeminal pain signaling in an injury-free model of migraine-like pain via activation of endocannabinoid receptors and repression of CGRP expression centrally. Hence, we propose that GSE may be beneficial as a complementary migraine therapeutic.
Reduced Hippocampal Volume and Neurochemical Response to Adult Stress Exposure in a Female Mouse Model of Urogenital Hypersensitivity
Authors: Brake Aaron D. , Yang Xiaofang , Lee Chu-Yu , Lee Phil , Keselman Paul , Eller Olivia C. , Choi In-Young , Harris Janna L. , Christianson Julie A.
Published: January 2022

Early life stress exposure significantly increases the risk of developing chronic pain syndromes and comorbid mood and metabolic disorders later in life. Structural and functional changes within the hippocampus have been shown to contribute to many early life stress-related outcomes. We have previously reported that adult mice that underwent neonatal maternal separation (NMS) exhibit urogenital hypersensitivity, altered anxiety- and depression-like behaviors, increased adiposity, and decreased gene expression and neurogenesis in the hippocampus. Here, we are using magnetic resonance imaging and spectroscopy (MRI and MRS) to further investigate both NMS- and acute stress-induced changes in the hippocampus of female mice. Volumetric analysis of the whole brain revealed that the left hippocampus of NMS mice was 0.038 mm3 smaller compared to naïve mice. MRS was performed only on the right hippocampus and both total choline (tCho) and total N-acetylaspartate (tNAA) levels were significantly decreased due to NMS, particularly after WAS. Phosphoethanolamine (PE) levels were decreased in naïve mice after WAS, but not in NMS mice, and WAS increased ascorbate levels in both groups. The NMS mice showed a trend toward increased body weight and body fat percentage compared to naïve mice. A significant negative correlation was observed between body weight and phosphocreatine levels post-WAS in NMS mice, as well as a positive correlation between body weight and glutamine for NMS mice and a negative correlation for naïve mice. Together, these data suggest that NMS in mice reduces left hippocampal volume and may result in mitochondrial dysfunction and reduced neuronal integrity of the right hippocampus in adulthood. Hippocampal changes also appear to be related to whole body metabolic outcomes.
Effect of Elective Cesarean Section on Children's Obesity From Birth to Adolescence: A Systematic Review and Meta-Analysis
Authors: Zhang Shanshan , Qin Xiaoyun , Li Peixuan , Huang Kun
Published: January 2022

Background

Elective cesarean section (ECS) is the most common reason for the increasing cesarean section rate worldwide, and it is reported to be related to adverse short-term and long-term outcomes in both mothers and infants. Findings on the association between ECS and overweight and obesity in children are controversial in recent studies. Therefore, we conducted a systematic review and meta-analysis to examine the effect of ECS on offspring's overweight and obesity.

Methods

PubMed, Science Direct, Web of Science, CNKI (China National Knowledge Infrastructure), Wanfang Database (in Chinese), and China Biology Medicine disc databases were searched using different combinations of three groups of keywords: “elective cesarean section,” “overweight/obesity,” and “children.” Nine cohort studies and 11 independent risk estimates were finally identified.

Results

We have observed significant association between ECS and children's obesity, the total pooled risk ratio (RR) being 1.10 (95% CI: 1.01–1.18; I2 = 32.4%). In subgroup analysis, ECS was found to be associated with the occurrence of obesity in preschoolers (RR = 1.12, 95% CI: 1.02–1.22; I2 = 16.8%). Furthermore, it revealed that ECS was related with the high risk of children's obesity where the rate of ECS exceeded 10%. No significant association was observed between ECS and children's overweight, and the RR was 1.12 (95% CI: 0.94–1.30; I2 = 55.6%).

Conclusions

Overall, it indicated that children born via ECS had an increased risk of later-life obesity. Given the global increase in childhood obesity, our findings would provide evidence-based reference for early life intervention on children's obesity.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021267211, identifier: CRD42021267211.
Fasting Intervention for Children With Unilateral Renal Tumors to Reduce Toxicity
Authors: Oudmaijer Christiaan A. J. , Boogaard Winnie M. C. van den , Komninos Daphne S. J. , Verwaaijen Emma J. , Santen Hanneke M. van , Lilien Marc R. , Hoeijmakers Jan H. J. , Wijnen Marc H. W. , Heuvel-Eibrink Marry M. van den , Vermeij Wilbert P.
Published: January 2022

Childhood renal tumors account for around 6% of all childhood cancers and 90% of these cases are Wilms tumor. In Europe, the SIOP-RTSG approach is considered standard of care and has resulted in five-year survival rates of over 90%. Efforts to decrease toxicity are now being pursued. Short-term fasting (STF), a short but strong reduction in calorie-intake, is associated with improved fitness, enhanced coping with acute physical stress and a lower risk of age-associated diseases. STF temporarily reduces growth to boost resilience, maintenance, and defense-mechanisms, by which toxic side-effects of (oxidative) damage and inflammation are largely prevented. Renal surgery for Wilms tumor carries a risk of acute kidney injury (AKI) and pediatric patients that had an episode of AKI are at increased risk for developing chronic renal disease. STF could mitigate surgery-induced stress and could further improve outcomes. We aim to investigate the effect of STF on renal function recovery after renal tumor surgery by conducting a single-center, prospective, randomized, non-blinded, intervention study. Children diagnosed with a unilateral renal tumor and opting for curative treatment are eligible for inclusion. The main study objective is to investigate the potential decrease in occurrence of AKI due to STF. Secondary objectives include renal function recovery, child's wellbeing, physical functioning, and feasibility of and adherence to STF in children with cancer.
Prognostic Implications of Pyroptosis-Related Gene Signatures in Lung Squamous Cell Carcinoma
Authors: Li Tingting , Liu Huanqing , Dong Chunsheng , Lyu Jun
Published: January 2022

Background: Lung squamous cell carcinoma (LUSC) has been a highly malignant tumor with very poor prognosis. It is confirmed that pyroptosis refers to the deaths of cells in a programmed and inflammatory manner. Nevertheless, the correlation between expression of genes related with pyroptosis and their prognosis remains uncertain in LUSC.

Methods: Utilization of The Cancer Genome Atlas (TCGA) cohort has been done for evaluating the prognostics of pyroptosis-related genes for survival and constructing a signature with multiple genes. The least absolute shrinkage and selection operator (LASSO) Cox regression was performed for establishing such pyroptosis-related gene signature.

Results: Eventually, identification of 28 genes in relation to pyroptosis was made in LUSC and healthy lung tissues. Upon the basis of these differentially-expressed genes (DEGs), the patients of LUSC can be divided into two subtypes. Nine gene signatures were established using LASSO. The surviving rate for low-risk group was apparently greater in contrast with the high-risk group (p < .001). According to our finding, risk score worked as an independent predictive factor of OS among LUSC sufferers in combination with clinical characteristics. In line with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, the enrichment of immunity-related genes and decreasing immunity status among the high-risk group.

Conclusion: Genes in relation with pyroptosis played an essential role in tumor immunity, which is capable of predicting the prognosis for LUSCs.
Analytical Model and Solution Illustrating Classical Optical Contribution to Giant Spectral Splitting in Strongly-Coupled Micro/nanocavity-atom System
Authors: Zeng Jian , Li Zhi-Yuan
Published: January 2022

Many experimental observations have shown remarkably large or even giant spectral splitting in strongly-coupled micro/nanocavity-atom systems. Popularly, such a spectral splitting has been attributed to the Rabi splitting, a pure quantum mechanical effect. However, there are disputes regarding whether the spectral splitting caused by multiple emitters, such as excitons in J-aggregate of molecules, is a pure quantum effect or also contributed by classical optical effect. In this work, we address this difficult problem by building a model physical system of a practical Fabry-Perot high-Q optical microcavity involving Lorentz-dispersion atoms. Very interestingly, by performing evaluation and estimate upon several strongly-coupled cavity-atom systems, we have found that the classical optical splitting and quantum Rabi splitting can be in the same order of magnitude. Our studies clearly indicate that the phenomenon of “giant Rabi splitting” that has been extensively observed in many experiments can also be caused by classic optical effects in addition to quantum mechanical effect. In some cases, the contribution by classic optical effects may be comparable to or even exceeding the contribution from quantum effects. We expect that this work can constructing the true and complete physics picture underlying strong light-matter interaction in a micro/nanocavity system.
Cryogenian Glacial Habitats as a Plant Terrestrialisation Cradle – The Origin of the Anydrophytes and Zygnematophyceae Split
Authors: Žárský Jakub , Žárský Vojtěch , Hanáček Martin , Žárský Viktor
Published: January 2022

For tens of millions of years (Ma), the terrestrial habitats of Snowball Earth during the Cryogenian period (between 720 and 635 Ma before present–Neoproterozoic Era) were possibly dominated by global snow and ice cover up to the equatorial sublimative desert. The most recent time-calibrated phylogenies calibrated not only on plants but on a comprehensive set of eukaryotes indicate that within the Streptophyta, multicellular charophytes (Phragmoplastophyta) evolved in the Mesoproterozoic to the early Neoproterozoic. At the same time, Cryogenian is the time of the likely origin of the common ancestor of Zygnematophyceae and Embryophyta and later, also of the Zygnematophyceae–Embryophyta split. This common ancestor is proposed to be called Anydrophyta; here, we use anydrophytes. Based on the combination of published phylogenomic studies and estimated diversification time comparisons, we deem it highly likely that anydrophytes evolved in response to Cryogenian cooling. Also, later in the Cryogenian, secondary simplification of multicellular anydrophytes and loss of flagella resulted in Zygnematophyceae diversification as an adaptation to the extended cold glacial environment. We propose that the Marinoan geochemically documented expansion of first terrestrial flora has been represented not only by Chlorophyta but also by Streptophyta, including the anydrophytes, and later by Zygnematophyceae, thriving on glacial surfaces until today. It is possible that multicellular early Embryophyta survived in less abundant (possibly relatively warmer) refugia, relying more on mineral substrates, allowing the retention of flagella-based sexuality. The loss of flagella and sexual reproduction by conjugation evolved in Zygnematophyceae and zygomycetous fungi during the Cryogenian in a remarkably convergent way. Thus, we support the concept that the important basal cellular adaptations to terrestrial environments were exapted in streptophyte algae for terrestrialization and propose that this was stimulated by the adaptation to glacial habitats dominating the Cryogenian Snowball Earth. Including the glacial lifestyle when considering the rise of land plants increases the parsimony of connecting different ecological, phylogenetic, and physiological puzzles of the journey from aquatic algae to terrestrial floras.
Dissecting the Root Phenotypic and Genotypic Variability of the Iowa Mung Bean Diversity Panel
Authors: Chiteri Kevin O. , Jubery Talukder Zaki , Dutta Somak , Ganapathysubramanian Baskar , Cannon Steven , Singh Arti
Published: January 2022

Mung bean [Vigna radiata (L.) Wilczek] is a drought-tolerant, short-duration crop, and a rich source of protein and other valuable minerals, vitamins, and antioxidants. The main objectives of this research were (1) to study the root traits related with the phenotypic and genetic diversity of 375 mung bean genotypes of the Iowa (IA) diversity panel and (2) to conduct genome-wide association studies of root-related traits using the Automated Root Image Analysis (ARIA) software. We collected over 9,000 digital images at three-time points (days 12, 15, and 18 after germination). A broad sense heritability for days 15 (0.22–0.73) and 18 (0.23–0.87) was higher than that for day 12 (0.24–0.51). We also reported root ideotype classification, i.e., PI425425 (India), PI425045 (Philippines), PI425551 (Korea), PI264686 (Philippines), and PI425085 (Sri Lanka) that emerged as the top five in the topsoil foraging category, while PI425594 (unknown origin), PI425599 (Thailand), PI425610 (Afghanistan), PI425485 (India), and AVMU0201 (Taiwan) were top five in the drought-tolerant and nutrient uptake “steep, cheap, and deep” ideotype. We identified promising genotypes that can help diversify the gene pool of mung bean breeding stocks and will be useful for further field testing. Using association studies, we identified markers showing significant associations with the lateral root angle (LRA) on chromosomes 2, 6, 7, and 11, length distribution (LED) on chromosome 8, and total root length-growth rate (TRL_GR), volume (VOL), and total dry weight (TDW) on chromosomes 3 and 5. We discussed genes that are potential candidates from these regions. We reported beta-galactosidase 3 associated with the LRA, which has previously been implicated in the adventitious root development via transcriptomic studies in mung bean. Results from this work on the phenotypic characterization, root-based ideotype categories, and significant molecular markers associated with important traits will be useful for the marker-assisted selection and mung bean improvement through breeding.
Promoting Mental Health in Healthcare Workers in Hospitals Through Psychological Group Support With Eye Movement Desensitization and Reprocessing During COVID-19 Pandemic: An Observational Study
Authors: Fogliato Elisa , Invernizzi Roberta , Maslovaric Giada , Fernandez Isabel , Rigamonti Vittorio , Lora Antonio , Frisone Enrico , Pagani Marco
Published: January 2022

Background

Psychological support was provided by the Eye Movement Desensitization and Reprocessing Integrative Group Treatment Protocol (EMDR-IGTP) within the hospitals in the Northern Italy in favor of healthcare workers during the COVID-19 pandemic. This study aimed at evaluating the effectiveness of treatment in terms of (a) symptomatology reduction related to peri- and post-traumatic stress; (b) clinical improvement over time; and (c) the maintenance of the achieved outcome over time.

Methods

The population was composed of healthcare workers who spontaneously requested psychological intervention in both the first and the second emergency waves. Statistical analyses were carried out to highlight the differences in Impact of Event-Revised (IES-R) and Post-Traumatic Growth Inventory (PTGI) before and after the group intervention.

Results

In both the first and the second waves, pre-treatment values are higher than post-treatment values for all dimensions of the IES-R. The results show that there are no significant differences between the first and the second wave with regard to the treatment effect. Healthcare workers maintained positive changes over time despite their prolonged exposure to an emergency and the possibility of retraumatization at the onset of a new emergency phase, irrespective of their working place. Healthcare workers who were treated in the first wave showed at the beginning of the second emergency wave less vulnerability and more resilience than those who were treated only in the second wave.

Pre-treatment scores of healthcare workers affected by COVID-19 are discussed.

Conclusion

COVID-19 had a significant impact on the well-being of healthcare workers who were working in hospitals. Psychological support in case of emergency is needed.
AI-Assisted Design Concept Exploration Through Character Space Construction
Authors: Sano Shin , Yamada Seiji
Published: January 2022

We propose an AI-assisted design concept exploration tool, the “Character Space Construction” (“CSC”). Concept designers explore and articulate the target product aesthetics and semantics in language, which is expressed using “Design Concept Phrases” (“DCPs”), that is, compound adjective phrases, and contrasting terms that convey what are not their target design concepts. Designers often utilize this dichotomy technique to communicate the nature of their aesthetic and semantic design concepts with stakeholders, especially in an early design development phase. The CSC assists this designers' cognitive activity by constructing a “Character Space” (“CS”), which is a semantic quadrant system, in a structured manner. A CS created by designers with the assistance of the CSC enables them to discern and explain their design concepts in contrast with opposing terms. These terms in a CS are retrieved and combined in the CSC by using a knowledge graph. The CSC presents terms and phrases as lists of candidates to users from which users will choose in order to define the target design concept, which is then visualized in a CS. The participants in our experiment, who were in the “arts and design” profession, were given two conditions under which to create DCPs and explain them. One group created and explained the DCPs with the assistance of the proposed CSC, and the other did the same task without this assistance, given the freedom to use any publicly available web search tools instead. The result showed that the group assisted by the CSC indicated their tasks were supported significantly better, especially in exploration, as measured by the Creativity Support Index (CSI).
Students’ Classroom Silence and Hopelessness: The Impact of Teachers’ Immediacy on Mainstream Education
Authors: Juma Osman , Husiyin Maysigul , Akhat Asat , Habibulla Imirhamza
Published: January 2022

The students’ silence in the classroom has lately become an area of attention of educators and scholars similarly; however, the factors influencing students’ classroom silence are not mainly scrutinized. This construct has been regarded as a problem of the communication between the educator and the learners that not only impact completing the teaching objectives in the classroom but also affect the nurturing of learners’ achievement. In addition, teachers positively have a noteworthy function in learners’ growth and progress and its behavior such as their immediacy remains a significant issue toward stimulating effective educational methods. Whilst teacher immediacy in a classroom setting is important, there is growing awareness about its important effect on learners’ silence and hopelessness. This review tries to provide some considerations about the relationship between teacher immediacy, both verbal and non-verbal, and students’ active silence and hopelessness. Successively, some suggestions are offered to lighten the practice of educators, learners, and teacher instructors.
Helping Others Helps Me: Prosocial Behavior and Satisfaction With Life During the COVID-19 Pandemic
Authors: Espinosa Juan C. , Antón Concha , Grueso Hinestroza Merlin Patricia
Published: January 2022

Prosocial behavior (PsB) and its effects have been analyzed in times of crisis and natural disasters, although never before in the face of such exceptional circumstances as those created by the COVID-19 pandemic. This research analyzes the role of PsB on satisfaction with life (SWL) in Colombia, considering the negative emotional impact of events that began in February 2020. We conduct an exploratory analysis using a sample of Colombia’s general population (N = 2,574; 53.2% women) with an average age of 44.66 years (SD = 15.36). Using the Classification Tree technique, we find that engaging in one or more PsBs (e.g., donating money or sharing food) enhances SWL and decreases the impact of negative emotions such as pessimism, indecisiveness, and irritability that have emerged during the COVID-19 pandemic. These findings are significant because they confirm the importance of life satisfaction as a personal resource for coping with complex situations and provide evidence of the benefits of PsB on one’s wellbeing.