bluuebunny/crossref_metadata_2025 huggingface dataset:
Relieving Cellular Energy Stress in Aging, Neurodegenerative, and Metabolic Diseases, SIRT1 as a Therapeutic and Promising Node
Authors: Fang Yang , Wang Xifeng , Yang Danying , Lu Yimei , Wei Gen , Yu Wen , Liu Xing , Zheng Qingcui , Ying Jun , Hua Fuzhou
Published: September 2021

The intracellular energy state will alter under the influence of physiological or pathological stimuli. In response to this change, cells usually mobilize various molecules and their mechanisms to promote the stability of the intracellular energy status. Mitochondria are the main source of ATP. Previous studies have found that the function of mitochondria is impaired in aging, neurodegenerative diseases, and metabolic diseases, and the damaged mitochondria bring lower ATP production, which further worsens the progression of the disease. Silent information regulator-1 (SIRT1) is a multipotent molecule that participates in the regulation of important biological processes in cells, including cellular metabolism, cell senescence, and inflammation. In this review, we mainly discuss that promoting the expression and activity of SIRT1 contributes to alleviating the energy stress produced by physiological and pathological conditions. The review also discusses the mechanism of precise regulation of SIRT1 expression and activity in various dimensions. Finally, according to the characteristics of this mechanism in promoting the recovery of mitochondrial function, the relationship between current pharmacological preparations and aging, neurodegenerative diseases, metabolic diseases, and other diseases was analyzed.
Ultra-Short Duration Hypothermia Prevents Intracranial Pressure Elevation Following Ischaemic Stroke in Rats
Authors: Omileke Daniel , Pepperall Debbie , Bothwell Steven W. , Mackovski Nikolce , Azarpeykan Sara , Beard Daniel J. , Coupland Kirsten , Patabendige Adjanie , Spratt Neil J.
Published: September 2021

There is a transient increase in intracranial pressure (ICP) 18–24 h after ischaemic stroke in rats, which is prevented by short-duration hypothermia using rapid cooling methods. Clinical trials of long-duration hypothermia have been limited by feasibility and associated complications, which may be avoided by short-duration cooling. Animal studies have cooled faster than is achievable in patients. We aimed to determine whether gradual cooling at a rate of 2°C/h to 33°C or 1°C/h to 34.5°C, with a 30 min duration at target temperatures, prevented ICP elevation and reduced infarct volume in rats. Transient middle cerebral artery occlusion was performed, followed by gradual cooling to target temperature. Hypothermia to 33°C prevented significant ICP elevation (hypothermia ΔICP = 1.56 ± 2.26 mmHg vs normothermia ΔICP = 8.93 ± 4.82 mmHg; p = 0.02) and reduced infarct volume (hypothermia = 46.4 ± 12.3 mm3 vs normothermia = 85.0 ± 17.5 mm3; p = 0.01). Hypothermia to 34.5°C did not significantly prevent ICP elevation or reduce infarct volume. We showed that gradual cooling to 33°C, at cooling rates achievable in patients, had the same ICP preventative effect as traditional rapid cooling methods. This suggests that this paradigm could be translated to prevent delayed ICP rise in stroke patients.
SYN1 Mutation Causes X-Linked Toothbrushing Epilepsy in a Chinese Family
Authors: Zhou Qin , Wang Jingwei , Xia Li , Li Rong , Zhang Qiumin , Pan Songqing
Published: September 2021

Toothbrushing epilepsy is a rare form of reflex epilepsy (RE) with sporadic incidence. To characterize the genetic profile of reflex epilepsy patients with tooth brushing-induced seizures in a Chinese family. Solo clinical whole-exome sequencing (WES) of the proband, a 37-year-old Chinese man, was performed to characterize the genetic etiology of toothbrushing epilepsy. Mutations in the maternal X-linked synapsin 1 (SYN1) identified in the proband and his family members were confirmed by Sanger sequencing. The pathogenicity of these mutations was determined using in silico analysis. The proband had four episodes of toothbrushing-induced seizures. The semiology included nausea, twitching of the right side of the mouth and face, followed by a generalized tonic-clonic seizure (GTCS). The proband's elder maternal uncle had three toothbrushing-induced epileptic seizures at the age of 26. The proband's younger maternal uncle had no history of epileptic seizures but had a learning disability and aggressive tendencies. We identified a deleterious nonsense mutation, c.1807C>T (p.Q603Ter), in exon 12 of the SYN1 gene (NM_006950), which can result in a truncated SYN1 phosphoprotein with altered flexibility and hydropathicity. This novel mutation has not been reported in the 1000G, EVS, ExAC, gnomAD, or HGMD databases. We identified a novel X-linked SYN1 exon 12 mutant gene in a Chinese family with toothbrushing epilepsy. Our findings provide novel insights into the mechanism of this complex form of reflex epilepsy that could potentially be applied in disease diagnosis.
Critical Period Plasticity as a Framework for Psychedelic-Assisted Psychotherapy
Authors: Lepow Lauren , Morishita Hirofumi , Yehuda Rachel
Published: September 2021

As psychedelic compounds gain traction in psychiatry, there is a need to consider the active mechanism to explain the effect observed in randomized clinical trials. Traditionally, biological psychiatry has asked how compounds affect the causal pathways of illness to reduce symptoms and therefore focus on analysis of the pharmacologic properties. In psychedelic-assisted psychotherapy (PAP), there is debate about whether ingestion of the psychedelic alone is thought to be responsible for the clinical outcome. A question arises how the medication and psychotherapeutic intervention together might lead to neurobiological changes that underlie recovery from illness such as post-traumatic stress disorder (PTSD). This paper offers a framework for investigating the neurobiological basis of PAP by extrapolating from models used to explain how a pharmacologic intervention might create an optimal brain state during which environmental input has enduring effects. Specifically, there are developmental “critical” periods (CP) with exquisite sensitivity to environmental input; the biological characteristics are largely unknown. We discuss a hypothesis that psychedelics may remove the brakes on adult neuroplasticity, inducing a state similar to that of neurodevelopment. In the visual system, progress has been made both in identifying the biological conditions which distinguishes the CP and in manipulating the active ingredients with the idea that we might pharmacologically reopen a critical period in adulthood. We highlight ocular dominance plasticity (ODP) in the visual system as a model for characterizing CP in limbic systems relevant to psychiatry. A CP framework may help to integrate the neuroscientific inquiry with the influence of the environment both in development and in PAP.
Perinatal Exposure of Bisphenol A Differently Affects Dendritic Spines of Male and Female Grown-Up Adult Hippocampal Neurons
Authors: Kawato Suguru , Ogiue-Ikeda Mari , Soma Mika , Yoshino Hinako , Kominami Toshihiro , Saito Minoru , Aou Shuji , Hojo Yasushi
Published: September 2021

Perinatal exposure to Bisphenol A (BPA) at a very low dose may modulate the development of synapses of the hippocampus during growth to adulthood. Here, we demonstrate that perinatal exposure to 30 μg BPA/kg per mother’s body weight/day significantly altered the dendritic spines of the grownup rat hippocampus. The density of the spine was analyzed by imaging of Lucifer Yellow-injected CA1 glutamatergic neurons in adult hippocampal slices. In offspring 3-month male hippocampus, the total spine density was significantly decreased by BPA exposure from 2.26 spines/μm (control, no BPA exposure) to 1.96 spines/μm (BPA exposure). BPA exposure considerably changed the normal 4-day estrous cycle of offspring 3-month females, resulting in a 4∼5 day estrous cycle with 2-day estrus stages in most of the subjects. In the offspring 3-month female hippocampus, the total spine density was significantly increased by BPA exposure at estrus stage from 2.04 spines/μm (control) to 2.25 spines/μm (BPA exposure). On the other hand, the total spine density at the proestrus stage was moderately decreased from 2.33 spines/μm (control) to 2.19 spines/μm (BPA exposure). Thus, after the perinatal exposure to BPA, the total spine density in males became lower than that in females. Concerning the BPA effect on the morphology of spines, the large-head spine was significantly changed with its significant decrease in males and moderate change in females.
Consumption of Coffee and Risk of Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis of Observational Studies
Authors: Ni Jiaying , Wang Ping , Zheng Tao , Lv Long , Peng Hao
Published: September 2021

Objective: The results from epidemiologic studies on the relationship between intake of coffee and the risk of gestational diabetes mellitus (GDM) remain inconclusive. A meta-analysis was performed to achieve a comprehensive finding regarding the association between intake of coffee and the risk of GDM.

Methods: PubMed, Scopus, ISI Web of Science, and Google Scholar were searched to find articles published up to August 2021. Observational studies that reported risk estimates [risk ratios (RRs), hazard ratios (HRs), and odds ratios (ORs)] for the association of consumption of coffee with the risk of GDM in pregnant women were included. Random effects model was applied to calculate summarized risk estimate and 95% CIs for the highest vs. lowest categories of intake of coffee.

Results: Seven observational studies (three cohort, two case-control, and two cross-sectional studies) with 75,607 participants and 1,625 women with GDM met the inclusion criteria. The meta-analysis of comparing the highest vs. lowest intake of coffee categories showed no significant association between intake of coffee and risk of GDM (summarized risk estimate: 0.89; 95% CI: 0.76, 1.05; I2 = 63.4%). Subgroup analysis showed that consumption of coffee had an inverse relationship with GDM in studies conducted in non-Asia countries (summarized risk estimate: 0.75; 95% CI: 0.58, 0.97; I2 = 6%).

Conclusion: This study has shown that high consumption of coffee did not decrease the risk of GDM. Furthermore, large-scale cohort studies are required to confirm our findings.
Downregulated Expression of CLEC9A as Novel Biomarkers for Lung Adenocarcinoma
Authors: Miao Fang , Lou Zhiguo , Ji Shuhua , Wang Dan , Sun Yaolan , Liu Huan , Yang Chenggang
Published: September 2021

Purpose

Abnormal CLEC9A expression is concerned with carcinogenesis. However, the role of CLEC9A in lung adenocarcinoma (LUAD) remains unknown. The goal of this study was to reveal the role of CLEC9A in LUAD based on bioinformatics and cellular functional experiments.

Materials and methods

Data available from The Cancer Genome Atlas (TCGA) were employed to study CLEC9A expression and mutations in LUAD. Expression and alterations of CLEC9A were analyzed using UALCAN and cBioPortal, respectively. Kaplan–Meier analysis was used to analyze the effect of CLEC9A on the survival of LUAD. Protein–protein interaction (PPI) network was built using GeneMANIA analysis. The similar genes of CLEC9A were obtained using GEPIA analysis, while co-expression genes correlated with CLEC9A were identified using LinkedOmics analysis. The effects of CLEC9A expression on immune cell infiltration was assessed. The effect of CLEC9A on the proliferation, apoptosis, cell cycle distribution, and invasion of human LUAD cells was detected in the LUAD cell line.

Results

CLEC9A was downregulated and the CLEC9A gene was often altered in LUAD. The survival of LUAD patients was correlated with the expression level of CLEC9A. The similar genes of CLEC9A were linked to functional networks involving positive regulation of interleukin-12 production, plasma membrane and CD40 receptor binding, primary immunodeficiency, intestinal immune network for IgA production, and cell adhesion molecules pathways. Cell cycle, apoptosis, EMT, and RAS/MAPK were significantly enriched pathways in positive and negative correlation genes with CLEC9A. A difference in the immune infiltration level of immune cell between the high and low CLEC9A expression groups was observed. Somatic cell copy number alternations (CNAs) of the CLEC9A, including arm-level gain and arm-level deletion, observably changed the infiltration levels of B cells, CD4+ T cells, macrophages, and neutrophils in LUAD. Except for LAG3, the expression of CD274, CTLA4, PDCD1, and TIGIT was positively correlated with the expression level of CLEC9A. After transfection, overexpression and knockdown of CLEC9A could affect the proliferation, apoptosis, cell cycle distribution, and invasion of LUAD cells.

Conclusion

CLEC9A is associated with prognosis and tumor immune microenvironment of LUAD, suggesting that CLEC9A may be considered as a novel biomarker for LUAD.
Radiomics in Oncology: A 10-Year Bibliometric Analysis
Authors: Ding Haoran , Wu Chenzhou , Liao Nailin , Zhan Qi , Sun Weize , Huang Yingzhao , Jiang Zhou , Li Yi
Published: September 2021

Objectives

To date, radiomics has been applied in oncology for over a decade and has shown great progress. We used a bibliometric analysis to analyze the publications of radiomics in oncology to clearly illustrate the current situation and future trends and encourage more researchers to participate in radiomics research in oncology.

Methods

Publications for radiomics in oncology were downloaded from the Web of Science Core Collection (WoSCC). WoSCC data were collected, and CiteSpace was used for a bibliometric analysis of countries, institutions, journals, authors, keywords, and references pertaining to this field. The state of research and areas of focus were analyzed through burst detection.

Results

A total of 7,199 pieces of literature concerning radiomics in oncology were analyzed on CiteSpace. The number of publications has undergone rapid growth and continues to increase. The USA and Chinese Academy of Sciences are found to be the most prolific country and institution, respectively. In terms of journals and co-cited journals, Scientific Reports is ranked highest with respect to the number of publications, and Radiology is ranked highest among co-cited journals. Moreover, Jie Tian has published the most publications, and Phillipe Lambin is the most cited author. A paper published by Gillies et al. presents the highest citation counts. Artificial intelligence (AI), segmentation methods, and the use of radiomics for classification and diagnosis in oncology are major areas of focus in this field. Test-retest statistics, including reproducibility and statistical methods of radiomics research, the relation between genomics and radiomics, and applications of radiomics to sarcoma and intensity-modulated radiotherapy, are frontier areas of this field.

Conclusion

To our knowledge, this is the first study to provide an overview of the literature related to radiomics in oncology and may inspire researchers from multiple disciplines to engage in radiomics-related research.
Progress of MRI Radiomics in Hepatocellular Carcinoma
Authors: Gong Xue-Qin , Tao Yun-Yun , Wu Yao–Kun , Liu Ning , Yu Xi , Wang Ran , Zheng Jing , Liu Nian , Huang Xiao-Hua , Li Jing-Dong , Yang Gang , Wei Xiao-Qin , Yang Lin , Zhang Xiao-Ming
Published: September 2021

Background

Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world and the third leading cause of cancer-related death. Although the diagnostic scheme of HCC is currently undergoing refinement, the prognosis of HCC is still not satisfactory. In addition to certain factors, such as tumor size and number and vascular invasion displayed on traditional imaging, some histopathological features and gene expression parameters are also important for the prognosis of HCC patients. However, most parameters are based on postoperative pathological examinations, which cannot help with preoperative decision-making. As a new field, radiomics extracts high-throughput imaging data from different types of images to build models and predict clinical outcomes noninvasively before surgery, rendering it a powerful aid for making personalized treatment decisions preoperatively.

Objective

This study reviewed the workflow of radiomics and the research progress on magnetic resonance imaging (MRI) radiomics in the diagnosis and treatment of HCC.

Methods

A literature review was conducted by searching PubMed for search of relevant peer-reviewed articles published from May 2017 to June 2021.The search keywords included HCC, MRI, radiomics, deep learning, artificial intelligence, machine learning, neural network, texture analysis, diagnosis, histopathology, microvascular invasion, surgical resection, radiofrequency, recurrence, relapse, transarterial chemoembolization, targeted therapy, immunotherapy, therapeutic response, and prognosis.

Results

Radiomics features on MRI can be used as biomarkers to determine the differential diagnosis, histological grade, microvascular invasion status, gene expression status, local and systemic therapeutic responses, and prognosis of HCC patients.

Conclusion

Radiomics is a promising new imaging method. MRI radiomics has high application value in the diagnosis and treatment of HCC.
Potential of Steroidal Alkaloids in Cancer: Perspective Insight Into Structure–Activity Relationships
Authors: Huang Ying , Li Gen , Hong Chong , Zheng Xia , Yu Haiyang , Zhang Yan
Published: September 2021

Steroidal alkaloids contain both steroidal and alkaloid properties in terms of chemical properties and pharmacological activities. Due to outstanding biological activities such as alkaloids and similar pharmacological effects to other steroids, steroidal alkaloids have received special attention in anticancer activity recently. Substituted groups in chemical structure play markedly important roles in biological activities. Therefore, the effective way to obtain lead compounds quickly is structural modification, which is guided by structure–activity relationships (SARs). This review presents the SAR of steroidal alkaloids and anticancer, including pregnane alkaloids, cyclopregnane alkaloids, cholestane alkaloids, C-nor-D-homosteroidal alkaloids, and bis-steroidal pyrazine. A summary of SAR can powerfully help to design and synthesize more lead compounds.
Impact of Inadequate Number of Lymph Nodes Examined on Survival in Stage II Colon Cancer
Authors: Wu Qi , Zhang Zhiyuan , Chen Yijiao , Chang Jiang , Jiang Yudong , Zhu Dexiang , Wei Ye
Published: September 2021

Background

Inadequate number of lymph nodes examined was not uncommon. We aimed to assess the clinical role of inadequate number of lymph nodes examined in stage II colon cancer.

Methods

The cancer data used in our study were obtained from the SEER (Surveillance, Epidemiology and End Results) program. Using the chi-square test, all the variables obtained in our study were compared based on whether patients had enough (≥12) lymph nodes examined. Kaplan–Meier analysis was used for overall survival (OS) analysis, and log-rank test was applied to compare different N stages with the total number of lymph nodes examined. Multivariate analysis was carried out by creating a Cox proportional hazard model to assess the prognostic roles of different variables.

Results

In total, 80,296 stage II/III colon cancer patients were recruited for our study. N0 stage with <8 lymph nodes examined would present with a worse prognosis compared to N1 stage (5-year OS rates, 51.6% vs. 57.1%, p < 0.001). Multivariate analyses indicated that OS of N0 stage with <8 lymph nodes examined was similar to that of N1 stage after adjusting for other recognized prognostic factors [hazard ratios (HRs) = 1.051, 95% confidence intervals (CIs) = 1.014–1.090, p = 0.018].

Conclusions

N0 stage with less than eight lymph nodes examined in stage II colon cancer presented with no better OS compared to that of N1 stage. Stage II colon cancer with less than eight lymph nodes examined needed to be given greater emphasis in clinical practice.
Precocious Puberty and Covid-19 Into Perspective: Potential Increased Frequency, Possible Causes, and a Potential Emergency to Be Addressed
Authors: Street Maria E. , Sartori Chiara , Catellani Cecilia , Righi Beatrice
Published: September 2021

A significant increase in precocious puberty, rapidly progressive puberty and precocious menarche has been reported in Italy since the initial lockdown because of the pandemic, and this could represent a new emergency to be addressed during this pandemic. There is a need, therefore, for further understanding and research. Many causes could account for this. Initially, it was thought that the changes in life-style, in screen time, and sleeping habits could be the cause but if considered individually these are insufficient to explain this phenomenon. Likely, changes in central nervous mediators, and an increase in catecholamines could contribute as a trigger, however, these aspects are poorly studied and understood as well as the real perceptions of these children. Finally, staying more indoors has certainly exposed these children to specific contaminants working as endocrine disruptors which could also have had an effect. It would be of utmost importance to compare this phenomenon worldwide with appropriate studies in order to verify what is happening, and gain a new insight into the consequences of the covid-19 pandemic and into precocious puberty and for future prevention.
Antiradical and Cytoprotective Properties of Allium nutans L. Honey Against CCL4-Induced Liver Damage in Rats
Authors: Sergazy Shynggys , Gulyayev Alexander , Amangeldiyeva Aidana , Nurgozhina Ayaulym , Nurgaziyev Madiyar , Shulgau Zarina , Chulenbayeva Laura , Khassenbekova Zhanagul , Kushugulova Almagul , Aljofan Mohamad
Published: September 2021

The aim of this study is determine the in vitro and in vivo antiradical properties and the cytoprotective activity of Allium nutans L. honey extract. The antiradical properties of the extracts were investigated in rabbit alveolar macrophages and human foreskin fibroblast (hFFs) cells in the presence of doxorubicin, a cytotoxic substance using DPPH and ABTS assays. The cytoprotective activities were determined using 18 Wistar rats divided into three different groups, a negative control, and two other groups with experimentally induced hepatotoxicity by a single intraperitoneal injection of 50% carbon tetrachloride (CCl4) oil solution. A positive control group, received drinking water only and an experimental group that was treated with Allium nutans L. honey extracts for 7 days. In vitro treatment with Allium nutans L. honey extracts resulted in 78% reduction in radical activity in DPPH and 91.6% inhibition using the ABTS. Also, honey extracts were able to preserve 100% of cell viability in the presence of the cytotoxic, doxorubicin. Furthermore, the treatment with honey extracts resulted in a significant reduction in damage to the structure of liver tissue, as well significant reduction in the levels of ALT and AST in the experimental group compared to the control group.
Real-World Experience of Bevacizumab as First-Line Treatment for Ovarian Cancer: The GINECO ENCOURAGE Cohort of 468 French Patients
Authors: Berton Dominique , Floquet Anne , Lescaut Willy , Baron Gabriel , Kaminsky Marie-Christine , Toussaint Philippe , Largillier Rémy , Savoye Aude-Marie , Alexandre Jérôme , Delbaldo Catherine , Malaurie Emmanuelle , Barletta Hugues , Bosacki Claire , Garnier-Tixidre Claire , Follana Philippe , Laharie-Mineur Hortense , Briac Levache Charles , Valenza Bruno , Dechartres Agnès , Mollon-Grange Delphine , Selle Frédéric
Published: September 2021

Introduction: Bevacizumab-containing therapy is considered a standard-of-care front-line option for stage IIIB–IV ovarian cancer based on results of randomized phase 3 trials. The multicenter non-interventional ENCOURAGE prospective cohort study assessed treatment administration and outcomes in the French real-world setting.

Patients and Methods: Eligible patients were aged ≥ 18 years with planned bevacizumab-containing therapy for newly diagnosed ovarian cancer. The primary objective was to assess the safety profile of front-line bevacizumab in routine clinical practice; secondary objectives were to describe patient characteristics, indications/contraindications for bevacizumab, treatment regimens and co-medications, follow-up and monitoring, progression-free survival, and treatment at recurrence. In this non-interventional study, treatment was administered as chosen by the investigator and participation in the trial had no influence on the management of the disease.

Results: Of 1,290 patients screened between April 2013 and February 2015, 468 were eligible. Most patients (86%) received bevacizumab 15 mg/kg every 3 weeks or equivalent, typically with carboplatin (99%) and paclitaxel (98%). The median duration of bevacizumab was 12.2 (range 0–28, interquartile range 6.9–14.9) months; 8% of patients discontinued bevacizumab because of toxicity. The most common adverse events were hypertension (38% of patients), fatigue (35%), and bleeding (32%). There were no treatment-related deaths. Most physicians (90%) reported blood pressure measurement immediately before each bevacizumab infusion and almost all (97%) reported monitoring for proteinuria before each bevacizumab infusion. Median progression-free survival was 17.4 (95% CI, 16.4–19.1) months. The 3-year overall survival rate was 62% (95% CI, 58–67%). The most commonly administered chemotherapies at recurrence were carboplatin and pegylated liposomal doxorubicin.

Discussion: Clinical outcomes and tolerability with bevacizumab in this real-life setting are consistent with randomized trial results, notwithstanding differences in the treated patient population and treatment schedule.

Clinical Trial Registration:ClinicalTrials.gov, Identifier NCT01832415.
Centipeda minima Extract Attenuates Dextran Sodium Sulfate-Induced Acute Colitis in Mice by Inhibiting Macrophage Activation and Monocyte Chemotaxis
Authors: Chan Brandon Dow , Wong Wing-Yan , Lee Magnolia Muk-Lan , Leung Tsz-Wing , Shum Tan-Yu , Cho William Chi-Shing , Chen Sibao , Tai William Chi-Shing
Published: September 2021

Inflammatory bowel disease (IBD) is an idiopathic inflammatory disease affecting the gastrointestinal tract. IBD is characterized by courses of relapse and remission, and remains incurable. Although multiple factors are related to the pathogenesis of IBD, disruption of intestinal mucosa homeostasis has been proposed to be a major contributor to IBD, and abnormal activation of immune cells is key for initiation of the inflammatory response. Macrophages are the most abundant immune cells in the intestine. Once activated, they are responsible for secretion of pro-inflammatory cytokines and chemokines to attract circulating monocytes to inflammatory sites, exacerbating the inflammatory response, and leading to tissue damage. Therefore, the suppression of activated macrophages, cytokine/chemokine production, and subsequent monocyte chemotaxis possesses great potential for the treatment of IBD. In our study, we have demonstrated the inhibitory effect of Centipeda minima total extract (CME) on the activation of NF-κB, STAT3, and MAPK signaling in LPS-stimulated RAW264.7 macrophages. In addition, we identified the significant suppressive effect of CME on CCL8 expression in activated macrophages, which potentially contributed to inhibition of monocyte chemotaxis. In the DSS-induced acute colitis mouse model, we have demonstrated the suppressive effect of CME on intestinal macrophage infiltration and its ameliorative effect in IBD. Altogether, we have provided evidence of the therapeutic effect of CME in IBD and the potential of CME for the treatment of IBD.
Assessment of the Perception of People Living With HIV Regarding the Quality of Outpatient Care at a Reference Facility in the Federal District, Brazil
Authors: Silva Andressa Wanneska Martins da , Meiners Micheline Marie Milward de Azevedo , Gallo Luciana Guerra , Oliveira Ana Flávia de Morais , Aridja Ursila Manga , Noronha Elza Ferreira
Published: September 2021

The effectiveness of antiretroviral treatment has transformed HIV infection into a chronic transmissible condition, requiring health systems to adapt in order to care for people living with HIV. The Chronic Care Model (CCM) is the gold standard for this type of care in many countries. Among its tools, the Patient Assessment of Chronic Illness Care (PACIC) questionnaire gives the patient’s perspective of the care provided. The aim of the present study was to adapt and apply, for the first time, the questionnaire to people living with HIV to determine their perception of the quality of care provided at a reference hospital in the Federal District of Brazil. This is a case study conducted in 2019 at a teaching hospital, with a convenience sample of 30 individuals treated for at least 1 year at the facility. The median PACIC score (3.5 with a range of 1.0–5.0) seems to suggest that the users perceive the outpatient care provided by the hospital as being basic. The “delivery system design/decision support” component was deemed the best (5.0, with a range of 1.0–5.0) and “follow-up/coordination” the worst (1.0, with a range of 1.0–5.0). The results suggest the need to improve the organization of care and make adequate use of community resources, in line with the CCM. The questionnaire makes it possible to determine the strengths and weaknesses of the care provided to people living with HIV and can be used as a planning and monitoring tool to improve management of the condition, with the contribution of the patient, in particular, thereby strengthening self-care.
Nonlinear Relationship Between Macrocytic Anemia and Decompensated Hepatitis B Virus Associated Cirrhosis: A Population-Based Cross-Sectional Study
Authors: Zhao Tian-Yu , Cong Qing-Wei , Liu Fang , Yao Li-Ying , Zhu Ying
Published: September 2021

Background: Mean corpuscular volume (MCV) is major used as an indicator for the differential diagnosis of anemia. Macrocytic anemia in decompensated cirrhosis is common. However, the relationship between macrocytic anemia and decompensated hepatitis B virus (HBV) associated cirrhosis has not been fully addressed.

Methods: In this cross-sectional study, a total of 457 patients diagnosed decompensated HBV associated cirrhosis who met all inclusion criteria from 2011 to 2018 were analyzed. Association between macrocytic anemia and the liver damaged (Model for End Stage Liver Disease (MELD) score) were examined using multiple logistic regression analyses and identified using smooth curve fitting.

Results: Compared with normocytic anemia, MCV and MELD are significantly positively correlated in macrocytic anemia (p < 0.001). A non-linear relationship of MCV and MELD association was found though the piecewise linear spline models in patients with decompensated HBV associated cirrhosis. MCV positive correlated with MELD when the MCV was greater than 98.2 fl (regression coefficient = 0.008, 95% CI 0.1, 0.4).

Conclusion: Macrocytic anemia may be a reliable predictor for mortality because it is closely related to the degree of liver damage in patients with decompensated HBV associated cirrhosis.
Lymphocytes: Versatile Participants in Acute Kidney Injury and Progression to Chronic Kidney Disease
Authors: Cao Chujin , Yao Ying , Zeng Rui
Published: September 2021

Background: Acute kidney injury (AKI) remains a major global public health concern due to its high morbidity and mortality. The progression from AKI to chronic kidney disease (CKD) makes it a scientific problem to be solved. However, it is with lack of effective treatments.

Summary: Both innate and adaptive immune systems participate in the inflammatory process during AKI, and excessive or dysregulated immune responses play a pathogenic role in renal fibrosis, which is an important hallmark of CKD. Studies on the pathogenesis of AKI and CKD have clarified that renal injury induces the production of various chemokines by renal parenchyma cells or resident immune cells, which recruits multiple-subtype lymphocytes in circulation. Some infiltrated lymphocytes exacerbate injury by proinflammatory cytokine production, cytotoxicity, and interaction with renal resident cells, which constructs the inflammatory environment and induces further injury, even death of renal parenchyma cells. Others promote tissue repair by producing protective cytokines. In this review, we outline the diversity of these lymphocytes and their mechanisms to regulate the whole pathogenic stages of AKI and CKD; discuss the chronological responses and the plasticity of lymphocytes related to AKI and CKD progression; and introduce the potential therapies targeting lymphocytes of AKI and CKD, including the interventions of chemokines, cytokines, and lymphocyte frequency regulation in vivo, adaptive transfer of ex-expanded lymphocytes, and the treatments of gut microbiota or metabolite regulations based on gut-kidney axis.

Key Message: In the process of AKI and CKD, T helper (Th) cells, innate, and innate-like lymphocytes exert mainly pathogenic roles, while double-negative T (DNT) cells and regulatory T cells (Tregs) are confirmed to be protective. Understanding the mechanisms by which lymphocytes mediate renal injury and renal fibrosis is necessary to promote the development of specific therapeutic strategies to protect from AKI and prevent the progression of CKD.
Src and Memory: A Study of Filial Imprinting and Predispositions in the Domestic Chick
Authors: Meparishvili Maia , Chitadze Lela , Lagani Vincenzo , McCabe Brian , Solomonia Revaz
Published: September 2021

Visual imprinting is a learning process whereby young animals come to prefer a visual stimulus after exposure to it (training). The available evidence indicates that the intermediate medial mesopallium (IMM) in the domestic chick forebrain is a site of memory formation during visual imprinting. We have studied the role of Src, an important non-receptor tyrosine kinase, in memory formation. Amounts of total Src (Total-Src) and its two phosphorylated forms, tyrosine-416 (activated, 416P-Src) and tyrosine-527 (inhibited, 527P-Src), were measured 1 and 24 h after training in the IMM and in a control brain region, the posterior pole of nidopallium (PPN). One hour after training, in the left IMM, we observed a positive correlation between the amount of 527P-Src and learning strength that was attributable to learning, and there was also a positive correlation between 416P-Src and learning strength that was attributable to a predisposition to learn readily. Twenty-four hours after training, the amount of Total-Src increased with learning strength in both the left and right IMM, and amount of 527P-Src increased with learning strength only in the left IMM; both correlations were attributable to learning. A further, negative, correlation between learning strength and 416P-Src/Total-Src in the left IMM reflected a predisposition to learn. No learning-related changes were found in the PPN control region. We suggest that there are two pools of Src; one of them in an active state and reflecting a predisposition to learn, and the second one in an inhibited condition, which increases as a result of learning. These two pools may represent two or more signaling pathways, namely, one pathway downstream of Src activated by tyrosine-416 phosphorylation and another upstream of Src, keeping the enzyme in an inactivated state via phosphorylation of tyrosine-527.
Risk Factors for Stiff Left Atrial Physiology 1 Year After Catheter Ablation of Atrial Fibrillation
Authors: Lee Jae-Hyuk , Kwon Oh-Seok , Yu Hee Tae , Kim Tae-Hoon , Uhm Jae-Sun , Joung Boyoung , Lee Moon-Hyoung , Pak Hui-Nam
Published: September 2021

Catheter ablation is the most effective rhythm control method for patients with atrial fibrillation (AF); however, it inevitably causes atrial tissue damage. We previously reported that AF catheter ablation (AFCA) increases left atrial (LA) pressure without changes in symptom scores. We hypothesized that extensive LA ablation increased the risk of stiff LA physiology. We included 1,720 patients (69.1% male, 60.0 [53.0–68.0] years old, 66.2% with paroxysmal AF) who underwent de novo AFCA and echocardiography before and 1-year after the procedure. Stiff LA physiology was defined, when the amount of the estimated pulmonary arterial pressure increase between the pre-procedural and the 1-year post-procedural follow-up echocardiography was >10 mmHg and when right ventricular systolic pressure (RVSP) was >35 mmHg at 1-year follow-up echocardiography. The failed rhythm control within 1 year was defined as recurrent AF despite using anti-arrhythmic drugs or cardioversion within a year of AFCA. We explored the incidence and risk factors for stiff LA physiology and the rhythm outcome of AFCA. Among the 1,720 patients, 64 (3.7%) had stiff LA physiology 1 year after AFCA. Stiff LA physiology was independently associated with diabetes (odds ratio [OR], 2.36 [95% CI, 1.14–4.87], p = 0.020), the ratio of the peak mitral flow velocity of the early rapid filling to the early diastolic velocity of the mitral annulus (E/Em; OR, 1.04 [95% CI, 1.00–1.10], p = 0.049), LA pulse pressure (Model 2: OR, 1.05 [95% CI, 1.00–1.11], p = 0.049), low LA voltage (OR, 0.36 [95% CI, 0.18–0.74], p = 0.005), empirical extra-pulmonary vein (PV) LA ablation (OR, 2.60 [95% CI, 1.17–5.74], p = 0.018), and radiofrequency (RF) ablation duration (Model 2: OR, 1.02 [95% CI, 1.01–1.03], p = 0.003). Although the incidence of post-AFCA stiff LA physiology was 3.7% and most of the cases were subclinical, the empirical extra-PV ablation was associated with this undesirable condition. In addition, patients who had low mean LA voltage before AFCA could be susceptible to stiff LA physiology.
The Bezold-Jarisch Reflex and The Inflammatory Response Modulation in Unanesthetized Endotoxemic Rats
Authors: Brognara Fernanda , Castania Jaci Airton , Ribeiro Aline Barbosa , Santos-Júnior Nilton Nascimento , Salgado Helio Cesar
Published: September 2021

Evidence indicates that the activation of the parasympathetic branch of the autonomic nervous system may be effective in treating inflammatory diseases. Previously, we have described that baroreflex activation displays anti-inflammatory properties. Analogous to the baroreflex, the Bezold-Jarisch reflex also promotes parasympathetic activation with simultaneous inhibition of the sympathetic system. Thus, the present study aimed to evaluate whether the activation of the Bezold-Jarisch reflex would also have the ability to reduce inflammation in unanesthetized rats. We used lipopolysaccharide (LPS) injection (5mg/kg, i.p.) to induce systemic inflammation in male Wistar Hannover rats and phenylbiguanide (PBG) administration (5μg/kg, i.v.) to activate the Bezold-Jarisch reflex. Spleen, heart, hypothalamus, and blood samples were collected to determine the levels of cytokines. Compared to baseline, PBG reduced the arterial pressure (115±2 vs. 88±5mmHg) and heart rate (380±7 vs. 114±26bpm), immediately after its administration, confirming the activation of the parasympathetic system and inhibition of the sympathetic system. From the immunological point of view, the activation of the Bezold-Jarisch reflex decreased the plasma levels of TNF (LPS: 775±209 vs. PBG + LPS: 248±30pg/ml) and IL-6 levels in the spleen (LPS: 39±6 vs. PBG + LPS: 24±4pg/mg of tissue). However, it did not change the other cytokines in the plasma or the other tissues evaluated. These findings confirm that the activation of the Bezold-Jarisch reflex can modulate inflammation and support the understanding that the cardiovascular reflexes regulate the immune system.
Identification of Quantitative Trait Loci Hotspots Affecting Agronomic Traits and High-Throughput Vegetation Indices in Rainfed Wheat
Authors: Rufo Rubén , López Andrea , Lopes Marta S. , Bellvert Joaquim , Soriano Jose M.
Published: September 2021

Understanding the genetic basis of agronomic traits is essential for wheat breeding programs to develop new cultivars with enhanced grain yield under climate change conditions. The use of high-throughput phenotyping (HTP) technologies for the assessment of agronomic performance through drought-adaptive traits opens new possibilities in plant breeding. HTP together with a genome-wide association study (GWAS) mapping approach can be a useful method to dissect the genetic control of complex traits in wheat to enhance grain yield under drought stress. This study aimed to identify molecular markers associated with agronomic and remotely sensed vegetation index (VI)-related traits under rainfed conditions in bread wheat and to use an in silico candidate gene (CG) approach to search for upregulated CGs under abiotic stress. The plant material consisted of 170 landraces and 184 modern cultivars from the Mediterranean basin. The collection was phenotyped for agronomic and VI traits derived from multispectral images over 3 and 2 years, respectively. The GWAS identified 2,579 marker-trait associations (MTAs). The quantitative trait loci (QTL) overview index statistic detected 11 QTL hotspots involving more than one trait in at least 2 years. A CG analysis detected 12 CGs upregulated under abiotic stress in six QTL hotspots and 46 downregulated CGs in 10 QTL hotspots. The current study highlights the utility of VI to identify chromosome regions that contribute to yield and drought tolerance under rainfed Mediterranean conditions.
The Impact of Breakdown in Filiation: The Instance of Children Exiled From Reunion Island to Mainland France Between 1962 and 1984
Authors: Feldman Marion , Mansouri Malika
Published: September 2021

The aim of this article was to show the consequences of breakdowns in filiation among people born between 1950 and 1970 on Reunion Island, who experienced particular traumas during their childhood. The research participants included 2,015 children exiled from Reunion Island to mainland France between 1962 and 1984 as part of a political project. Most of them we adopted, others were placed in foster families, foster homes, or farms. The forced exile was orchestrated by the French social services in charge of child protection (DDASS). Structured interviews were conducted for 13 people exiled when they were between 2 and 15years old. The interviews were transcribed and then analysed. The results show that these children were exposed to abuse in their filiation through a series of traumas. For them, this abuse is still active today as the French government has not yet acknowledged the suffering of these children. The participants displayed numerous psychic disorders linked to their abandonment. They are still experiencing difficulties in assuming their identity, and these difficulties are transmitted to the next generation. Analysis of the impact of these filiation breakdowns leads the present researchers to suggest a specific clinical setting, based on a focus group, in other words a group therapy aiming to generate a group narrative process.
People Judge Discrimination Against Women More Harshly Than Discrimination Against Men – Does Statistical Fairness Discrimination Explain Why?
Authors: Feess Eberhard , Feld Jan , Noy Shakked
Published: September 2021

Previous research has shown that people care less about men than about women who are left behind. We show that this finding extends to the domain of labor market discrimination: In identical scenarios, people judge discrimination against women more morally bad than discrimination against men. This result holds in a representative sample of the US population and in a larger but not representative sample of Amazon Mechanical Turk (Mturk) respondents. We test if this gender gap is driven by statistical fairness discrimination, a process in which people use the gender of the victim to draw inferences about other characteristics which matter for their fairness judgments. We test this explanation with a survey experiment in which we explicitly hold information about the victim of discrimination constant. Our results provide only mixed support for the statistical fairness discrimination explanation. In our representative sample, we see no meaningful or significant effect of the information treatments. By contrast, in our Mturk sample, we see that providing additional information partly reduces the effect of the victim’s gender on judgment of the discriminator. While people may engage in statistical fairness discrimination, this process is unlikely to be an exhaustive explanation for why discrimination against women is judged as worse.
Occupational Depression, Cognitive Performance, and Task Appreciation: A Study Based on Raven’s Advanced Progressive Matrices
Authors: Bianchi Renzo , Schonfeld Irvin Sam
Published: September 2021

The Occupational Depression Inventory (ODI) was recently developed to assess depressive symptoms that individuals specifically attribute to their work. Research on the criterion validity of the instrument is still in its infancy. In this study, we examined whether the ODI predicted performance on, and appreciation of, a cognitively challenging test. In light of the link established between clinical depression and neuropsychological impairment, and considering that individuals with depressive symptoms are more likely to feel helpless under challenging circumstances, we hypothesized that occupational depression would be associated with poorer cognitive performance and a darkened appreciation of the task undertaken. We relied on a sample of 1,359 educational staff members. We used an abridged version of Raven’s Advanced Progressive Matrices (RAPMs) as a cognitively challenging task and measure of cognitive performance. RAPMs assess so-called eductive ability (meaning-making and problem-solving abilities) through items of various degrees of difficulty. Transient mood was assessed with a three-item measure before RAPMs were administered. Task appreciation was assessed with a single-item measure after the completion of RAPMs. We found occupational depression to be negatively linked to cognitive performance. A two-step cluster analysis, in which ODI and RAPMs scores were used as classifiers, revealed two profiles of respondents. The first profile was characterized by relatively low levels of depressive symptoms and high levels of cognitive performance; the second profile, by relatively high levels of depressive symptoms and low levels of cognitive performance. The two profiles differed strongly from one another, as indexed by Cohen’s ds of 2.492 regarding depressive symptoms and 1.263 regarding cognitive performance. As anticipated, occupational depression predicted a darkened appreciation of the test. The association remained statistically significant, and largely unchanged, controlling for pretest mood and test performance. The highest levels of depressive symptoms were observed among individuals evaluating the task as “frustrating” and “discouraging.” Our study suggests that occupational depression predicts poorer cognitive performance and a negativized experience of cognitive challenge. Such features may be part of a self-sustaining loop fostering the maintenance of depressive symptoms. The extent to which the ODI predicts performance in the work context needs to be investigated.
Downtrends in Offside Offenses Among ‘The Big Five’ European Football Leagues
Authors: Zhao Yangqing
Published: September 2021

This study examined the evolution of offside offenses and pass performance across a 10-season period in the top five European soccer leagues. Match performance observations (n = 18 259) were analysed for emergent trends. Two-way ANOVA analyses revealed significant league and seasonal differences among the five leagues (medium effect size). The total offside offenses committed during a match experienced a clear decline during the 10 seasons. In contrast, moderate increases were evident for all passing differential variables. Offside offenses per match were higher in the German Bundesliga and Spanish La Liga than in the English Premier League and France Ligue 1. However, the English Premier League had the greatest value in the touch differential, pass differential, successful pass differential, and key pass differential among all leagues. It is important to note that the number of offside offenses fell after the implementation of VAR.