bluuebunny/crossref_metadata_2025_split huggingface dataset:
Secretory autophagy promotes Rab37-mediated exocytosis of tissue inhibitor of metalloproteinase 1
Authors: Wu Shan-Ying , Chen Jia-Wen , Liu Hsi-Yu , Wang Yi-Ching , Chu Yeh-Shiu , Huang Chi-Ying , Lan Kai-Ying , Liu Hsiao-Sheng , Lan Sheng-Hui 
Published: December 2022

Abstract
Background
Rab37-mediated exocytosis of tissue inhibitor of metalloproteinase 1 (TIMP1), an inflammatory cytokine, under serum-depleted conditions which leads to suppression of lung cancer cell metastasis has been reported. Starvation is also a stimulus of autophagic activity. Herein, we reveal that starvation activates Rab37 and induces autophagy.

Methods
We used an overexpression/knockdown system to determine the relationship between autophagy and Rab37 in vitro and in vivo. The autophagy activity was detected by immunoblotting, transmission electron microscope, autophagosome purification, and immunofluorescence under the confocal microscope. Lung-to-lung metastasis mouse model was used to clarify the role of autophagy and Rab37 in lung cancer. Clinical lung cancer patient specimens and an online big database were analyzed.

Results
Initially, we demonstrated that active-form Rab37 increased LC3-II protein level (the marker of autophagosome) and TIMP1 secretion. Accordingly, silencing of Rab37 gene expression alleviated Rab37 and LC3-II levels as well as TIMP1 secretion, and induction of autophagy could not increase TIMP1 exocytosis under such conditions. Moreover, silencing the Atg5 or Atg7 gene of lung cancer cells harboring active-mutant Rab37 (Q89L) led to decreased autophagy activity and TIMP1 secretion. In the lung-to-lung metastasis mouse model, increased TIMP1 expression accompanied by amiodarone-induced autophagy led to decreased tumor nodules and cancer cell metastasis. These phenomena were reversed by silencing the Atg5 or Atg7 gene. Notably, increasing autophagy activity alone showed no effect on TIMP1 secretion under either Rab37 or Sec22b silencing conditions. We further detected colocalization of LC3 with either Rab37 or TIMP1, identified Rab37 and Sec22b proteins in the purified autophagosomes of the lung cancer cells harboring the active-form Rab37 gene, and confirmed that these proteins are involved in the secretion of TIMP1. We reveal that autophagic activity was significantly lower in the tumors compared to the non-tumor parts and was associated with the overall lung cancer patient survival rate.

Conclusions
We are the first to report that autophagy plays a promoting role in TIMP1 secretion and metastasis in a Rab37-dependent manner in lung cancer cells and the lung-to-lung mouse model.
Antibodies in action: the role of humoral immunity in the fight against atherosclerosis
Authors: Taylor Joshua A. , Hutchinson Mark A. , Gearhart Patricia J. , Maul Robert W. 
Published: December 2022

AbstractThe sequestering of oxidation-modified low-density lipoprotein by macrophages results in the accumulation of fatty deposits within the walls of arteries. Necrosis of these cells causes a release of intercellular epitopes and the activation of the adaptive immune system, which we predict leads to robust autoantibody production. T cells produce cytokines that act in the plaque environment and further stimulate B cell antibody production. B cells in atherosclerosis meanwhile have a mixed role based on subclass. The current model is that B-1 cells produce protective IgM antibodies in response to oxidation-specific epitopes that work to control plaque formation, while follicular B-2 cells produce class-switched antibodies (IgG, IgA, and IgE) which exacerbate the disease. Over the course of this review, we discuss further the validation of these protective antibodies while evaluating the current dogma regarding class-switched antibodies in atherosclerosis. There are several contradictory findings regarding the involvement of class-switched antibodies in the disease. We hypothesize that this is due to antigen-specificity, and not simply isotype, being important, and that a closer evaluation of these antibodies’ targets should be conducted. We propose that specific antibodies may have therapeutical potential in preventing and controlling plaque development within a clinical setting.
Factors associated with exclusive breastfeeding at discharge during the COVID-19 pandemic in 17 WHO European Region countries
Authors: Chertok Ilana Azulay , Artzi-Medvedik Rada , Arendt Maryse , Sacks Emma , Otelea Marina Ruxandra , Rodrigues Carina , Costa Raquel , Linden Karolina , Zaigham Mehreen , Elden Helen , Drandic Daniela , Grylka-Baeschlin Susanne , Miani Céline , Valente Emanuelle Pessa , Covi Benedetta , Lazzerini Marzia , Mariani Ilaria 
Published: December 2022

Abstract
Background
Exclusive breastfeeding is the optimal infant nutrition, providing infants immunoprotection against many diseases including SARS-CoV-2 infection. Restrictions during the COVID-19 pandemic may have negatively affected breastfeeding practices in maternity care facilities. The aims of the study were to examine exclusive breastfeeding rates at discharge over time and to identify factors associated with exclusive breastfeeding during the pandemic.

Methods
A cross-sectional survey was conducted among mothers who gave birth in a maternity care facility in the World Health Organization (WHO) European Region countries during the COVID-19 pandemic. The socio-ecological model was employed to examine intrapersonal, interpersonal, organizational, and community/society factors associated with maternal report of exclusive breastfeeding at the time of discharge.

Results
There were 26,709 participating mothers from 17 European Region countries who were included in the analysis. Among the mothers, 72.4% (n = 19,350) exclusively breastfed and 27.6% (n = 7,359) did not exclusively breastfeed at discharge. There was an overall decline in exclusive breastfeeding rates over time (p = 0.015) with a significantly lower rate following the publication of the WHO breastfeeding guidelines on 23 June 2020 (AOR 0.88; 95% CI 0.82, 0.94). Factors significantly associated with exclusive breastfeeding outcomes in the logistic regression analysis included maternal age, parity, education, health insurance, mode of birth, inadequate breastfeeding support, lack of early breastfeeding initiation, lack of full rooming-in, birth attendant, perceived healthcare professionalism and attention, facility room cleanliness, timing of birth, and location of birth.

Conclusions
Results from the study indicate the decline in exclusive breastfeeding rates in the WHO European Region during the COVID-19 pandemic. Using the socio-ecological model to identify factors associated with breastfeeding outcomes facilitates an integrated and holistic approach to address breastfeeding needs among women across the region. These findings demonstrate the need to augment breastfeeding support and to protect exclusive breastfeeding among mother-infant dyads, in an effort to reverse the declining exclusive breastfeeding rates. The study highlights the need to educate mothers and their families about the importance of exclusive breastfeeding, reduce maternal-infant separation, increase professional breastfeeding support, and follow evidence-based practice guidelines to promote breastfeeding in a comprehensive and multi-level manner.

Trial registration number
Clinical Trials NCT04847336.
Exploration of the mechanisms underlying the beneficial effect of Luo Tong formula on retinal function in diabetic rats via the “gut microbiota–inflammation–retina” axis
Authors: Di Sha , Yao Chensi , Qiao Liping , Li Xiuyang , Pang Bing , Lin Jiaran , Wang Jia , Li Min , Tong Xiaolin 
Published: December 2022

Abstract
Background
Diabetic retinopathy (DR) is a common microvascular complication of diabetes. Luo Tong formula (LTF), a classical traditional Chinese medicine (TCM) prescription, consists of four plants that have been widely and effectively used to treat DR. Previous work in our laboratory has confirmed that LTF can effectively ameliorate DR. However, the potential mechanism underlying the therapeutic effect of LTF on DR has not been fully elucidated. To explore the potential mechanism of action through which LTF prevents and alleviates DR from an inflammation and gut microbiota perspective.

Materials and methods
Metabolite profiling of LTF was performed using liquid chromatography–mass spectrometry (LC–MS) and gas chromatography–mass spectrometry (GC–MS). Type 1 diabetes was induced in male Sprague Dawley (SD) rats via tail vein injection of 45 mg/kg streptozotocin. Next, 100 SD rats were randomly divided into four groups, normal control; diabetic control; diabetic + insulin + calcium dobesilate; and diabetic + insulin + LTF. After 12 weeks of treatment, glucose metabolism, fundus oculi, blood-retinal barrier permeability, retinal thickness, microvascular damage, as well as cell junction expression in retinas were measured and the changes observed in different groups were compared. Finally, the alteration in gut microbiota and inflammatory cytokine expression in serum and tissues were monitored, and their correlation was analyzed.

Results
A total of 1024 valid peaks were obtained for LTF using GC–MS. The HbA1c and fasting blood glucose (FBG) levels in the LTF group were slightly decreased. LTF exerted protective effects on fundus oculi and the retina structure to different degrees. LTF attenuated systemic and local retinal inflammation by significantly decreasing the levels of seven pro-inflammatory cytokines, including ICAM-1, IL-6, IL-8, MCP-1, VCAM-1, VEGF, and IL-1β. LTF restored the intestinal microbiota of diabetic rats to levels that were similar to those of normal rats. Further analysis revealed that Enterobacteriales, Prevotellaceae, Enterobacteriaceae, Bacteroides, and Klebsiella were significantly and positively correlated with the inflammatory factors in DR after LTF treatment.

Conclusions
Our results revealed the mechanisms underlying the preventive effects of LTF on DR development and progression. LTF inhibited pathological changes in retinal histopathology, cell composition, and cell junction proteins while effectively ameliorating systemic and local retinal inflammation via regulating pivotal gut microbiota.
Post-transplant cyclophosphamide for GVHD prophylaxis in pediatrics with chronic active Epstein-Barr virus infection after haplo-HSCT
Authors: Luo Rongmu , Zhang Xiaomei , Wang Ya , Man Qihang , Gu Wenjing , Tian Zhengqin , Wang Jingbo 
Published: December 2022

Abstract
Background
Chronic active Epstein-Barr virus infection (CAEBV) is a rare but life-threatening progressive disease. Human leukocyte antigen (HLA)-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is the best choice as sometimes HLA-matched donor is not accessible. However, graft-versus-host-disease (GVHD) following transplantation remains a major cause of treatment failure and elevated mortality. Post-transplant cyclophosphamide (PTCy) has recently emerged for effective GVHD prophylaxis in a haploidentical setting in many hematologic malignancies. Here, we report the performance of PTCy for GVHD prophylaxis in a series of CEABV patients treated with haplo-HSCT.

Methods
Consecutive pediatric CAEBV patients who were treated with haplo-HSCT and give PTCy for GVHD prophylaxis were analyzed. 1-year GVHD and relapse-free survival (GRFS), overall survival (OS) and cumulative incidence of moderate-to-severe chronic GVHD (cGVHD) were estimated.

Results
A total of 8 patients ranging from 2 to 15 years old were included. Among them, 4 patients had early complications after haplo-HSCT. Counts of T-cell subsets increased within 6 months post transplantation, indicating an immune reconstitution. Only 1 patient developed grade II acute GVHD, and 2 patients had moderate cGVHD. One patient died from diffuse alveolar hemorrhage within the first year after transplantation. The 1-year GRFS rate, OS rate and cumulative incidence of moderate-to-severe cGVHD were 62.5%, 87.5% and 25.0%, respectively.

Conclusion
Our findings suggest that, among CAEBV patients treated with haplo-HSCT, PTCy may be an alternative choice for the prevention of GVHD.
In vivo models of Escherichia coli infection in poultry
Authors: Kromann Sofie , Jensen Henrik Elvang 
Published: December 2022

AbstractEscherichia coli represents a significant challenge to the poultry industry due to compromised animal welfare, vast productivity losses, elevated mortality, and increased use of antimicrobial compounds. Therefore, effective preventive strategies and insight into the pathogenesis and disease mechanisms of colibacillosis are essential to secure a healthy poultry production. Consequently, discriminative in vivo models of colibacillosis are prerequisite tools for evaluating e.g., preventive measures, exploring novel treatments and understanding disease development. Numerous models of colibacillosis are applied for experimental studies in poultry. Yet, few studies provide a proper characterisation of the model enabling other authors to reproduce experiments or use the model in general. The present paper provides a literature review on avian in vivo models of primary colibacillosis.
The importance of familial risk factors in children with ADHD: direct and indirect effects of family adversity, parental psychopathology and parenting practices on externalizing symptoms
Authors: Jendreizik Lea Teresa , Hautmann Christopher , von Wirth Elena , Dose Christina , Thöne Ann-Kathrin , Treier Anne-Katrin , Banaschewski Tobias , Becker Katja , Brandeis Daniel , Geissler Julia , Hebebrand Johannes , Hohmann Sarah , Holtmann Martin , Huss Michael , Jans Thomas , Kaiser Anna , Millenet Sabina , Poustka Luise , Schneider Priska , Döpfner Manfred 
Published: December 2022

Abstract
Background
Children experiencing unfavorable family circumstances have an increased risk of developing externalizing symptoms. The present study examines the direct, indirect and total effects of family adversity, parental psychopathology, and positive and negative parenting practices on symptoms of attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) in children with ADHD.

Methods
Data from 555 children (M = 8.9 years old, 80.5% boys) who participated in a multicenter study on the treatment of ADHD (ESCAschool) were analyzed using structural equation modeling (SEM).

Results
The SEM analyses revealed that (a) family adversity and parental psychopathology are associated with both child ADHD and ODD symptoms while negative parenting practices are only related to child ODD symptoms; (b) family adversity is only indirectly associated with child ADHD and ODD symptoms, via parental psychopathology and negative parenting practices; (c) the detrimental effect of negative parenting practices on child ADHD and ODD symptoms is stronger in girls than in boys (multi-sample SEM); (d) there are no significant associations between positive parenting practices and child ADHD or ODD symptoms.

Conclusions
Family adversity, parental psychopathology, and negative parenting practices should be routinely assessed by clinicians and considered in treatment planning.
Trial registration (18th December 2015): German Clinical Trials Register (DRKS) DRKS00008973.
Predictors of participants’ retention—socioeconomic factors or nonadherence: insights from a urological clinical prospective study
Authors: Wheeler Allison J. , Garg Harshit , Kaushik Dharam , Mansour Ahmed , Pruthi Deepak , Liss Michael A. 
Published: December 2022

Abstract
Background
To investigate various patient-level variables, specifically socioeconomic status, as risk factors for withdrawal in a recently completed clinical study. We specifically investigated a non-interventional prospective study assessing the role of novel imaging as a biomarker for cancer upgradation in prostate cancer for this objective.

Methods
In this retrospective analysis, we assessed the association between various patient-level factors including clinic-demographic factors, socioeconomic status, and the number of non-adherences with the participants’ retention or withdrawal from the study. For socioeconomic status (SES), we used the zip code–based Economic Innovation Group Distressed Community Index (DCI) which classifies into five even distress tiers: prosperous, comfortable, mid-tier, at-risk, or distressed. Low SES was defined as those with a DCI Distress tier of at-risk or distressed. We compared values between the two retention and withdrawal groups using t-test, chi-square test, and logistic regression analysis.

Results
Of 273 men screened, 123 men were enrolled. Among them, 86.2% (106/123) retained through the study whereas 13.8% (17/123) withdrew from the study. The mean (SD) age was 64 (6.4) years. Overall, 31.7% (39/123) were Hispanics and 24.3% (30/123) were African Americans. The median (IQR) DCI score was 34 (10.3, 68.1) and 30.8% (38/123) of patients belonged to low SES. The median DCI score in participants who retained in the study was statistically similar to those who withdrew from the study (p=0.4). Neither the DCI tiers (p=0.7) nor the low SES (p=0.9) were associated with participants’ retention or withdrawal of the study. In terms of non-adherence, all participants in the withdrawn group had at least one non-adherent event compared to 48.1% in the retained group (p<0.001). Repetitive non-adherence was significantly higher in participants who withdrew from the study vs those who retained in the study [88.2% vs 16.9%, p <0.001]. On multivariate logistic regression analysis, the number of non-adherences (OR=12.5, p<0.001) and not DCI (OR=0.99, p=0.7) appeared to be an independent predictor for participants’ retention or withdrawal from the study.

Conclusions
Expanding diverse inclusion and limiting withdrawal with real-time non-adherence monitoring will lead to more efficient clinical research and greater generalizability of results.
Group psychoeducation for persons with bipolar disorder in Rwanda: a study protocol for a randomized controlled trial
Authors: Musoni-Rwililiza E. , Arnbjerg C. J. , Murekatete C. , Carlsson J. , Kallestrup P. , Gishoma D. 
Published: December 2022

Abstract
Background
The efficacy of psychoeducation as an add-on treatment to pharmacotherapy is well documented in treating symptoms and in relapse prevention for persons with bipolar disorder in western countries. Yet, no studies on psychosocial interventions for persons with bipolar disorder have been conducted in a low-income country in Africa.

Aim
To develop a bipolar group psychoeducation program contextualized to the Rwandese setting, and determine its effect on symptom severity, medical adherence, and internalized stigma.

Methods
A culturally adapted guide manual was developed by local mental health professionals, including nurses, psychologists, and medical doctors. In-depth interviews with participants were held prior to and will be held following the intervention to address the cultural aspect of living with bipolar disease and the impact of the program. A two-armed randomized controlled trial has been set up at the tertiary mental health hospitals in Rwanda, with an intervention and a waiting list arm. A sample size of at least 50 in each arm was calculated as a requirement. The study’s primary outcome measure will be the difference in relapse rate measured on the Young Mania Rating Scale and Hamilton Depression Scale-17. Differences in mean change on scales for medical adherence and internalized stigma will be secondary outcomes. Data will be analyzed according to the intention-to-treat principle. Participants will be assessed subsequently at baseline, at the end of the intervention period, and three months and 12 months post-intervention.

Discussion
This study will be one of the first intervention trials on bipolar disorder in a low-income country. If proven successful in reducing morbidity and increasing the quality of life in persons with bipolar disorder, it is anticipated that the psychoeducation program can be implemented at the district and community level and act as inspiration for other low-resource settings.

Trial registration
ClinicalTrials.gov NCT04671225. Registered on November 2020.
Synthesis, antimalarial, antileishmanial evaluation, and molecular docking study of some 3-aryl-2-styryl substituted-4(3H)-quinazolinone derivatives
Authors: Seifu Girma Worku , Birhan Yihenew Simegniew , Beshay Botros Youssef , Hymete Ariaya , Bekhit Adnan Ahmed 
Published: December 2022

AbstractQuinazolinones are a diverse group of nitrogen-containing heterocyclic compounds with promising antimalarial and antileishmanial activities. Herein, some 3-aryl-2-styryl substituted-4(3H)-quinazolinones were synthesized via cyclization, condensation, and hydrolysis reactions. 1H NMR, FTIR and elemental microanalysis was used to verify the structures of the synthesized compounds. The in vivo antimalarial and in vitro antileishmanial activities of the target compounds were investigated using mice infected with Plasmodium berghi ANKA and Leishmania donovani strain, respectively. Among the test compounds, 8 and 10 showed better antimalarial activities with percent suppression of 70.01 and 74.18, respectively. In addition, (E)-2-(4-nitrostyryl)-3-phenylquinazolin-4(3H)-one (6) showed promising antileishmanial activity (IC50 = 0.0212 µg/mL). It is two and 150 times more active than the standard drugs amphotericin B deoxycholate (IC50 = 0.0460 µg/mL) and miltefosine (IC 50 = 3.1911 µg/mL), respectively. Its superior in vitro antileishmanial activity was supported by a molecular docking study conducted in the active site of Lm-PTR1. Overall, the synthesized 3-aryl-2-styryl substituted-4(3H)-quinazolinones showed promising antileishmanial and antimalarial activities and are desirable scaffolds for the synthesis of different antileishmanial and antimalarial agents.
Gender differences in the association between insulin resistance and chronic kidney disease in a Chinese population with metabolic syndrome
Authors: Lin Chieh-An , Li Wen-Cheng , Lin Szu-Yu , Chen Yi-Chuan , Yu Wei , Huang Hsiung-Ying , Xiong Xue-Jie , Chen Jau-Yuan 
Published: December 2022

Abstract
Background
Insulin resistance (IR) was reported to be associated with renal function impairment, but little is known about the gender difference. Hence, our study aimed to investigate the relationship between IR (estimated by the homeostasis model assessment of IR (HOMA-IR) index) and chronic kidney disease (CKD) in a Chinese population with metabolic syndrome (MetS) and discern whether there was any gender disparity or not.

Methods
This retrospective cross-sectional study enrolled 13,638 men and 10,450 women who received health examinations from 2013 to 2016 at Xiamen Chang Gung Hospital. Among the participants, 3,253 men (64.3%) and 1,808 women (35.7%) who had MetS and met the inclusion criteria were included for analysis. Spearman’s correlation was conducted to analyze the relationship between HOMA-IR and cardio-metabolic risk factors. Multivariable linear regression was analyzed to explore the relationship between HOMA-IR and cardio-metabolic variables. Logistic regression analysis was performed to assess the association between HOMA-IR and CKD.

Results
The median HOMA-IR and prevalence of CKD was 2.2 and 11.31%, respectively, for men and 2.09 and 15.93%, respectively, for women. In multivariable linear regression analysis, HOMA-IR was significant associated with estimated GFR, albumin/creatinine ratio in men. Multivariable logistic regression revealed a significant difference between HOMA-IR value and the prevalence of CKD in men but not in women (odds ratio in male = 1.21; 95% CI 1.14–1.28, p ≤ 0.001; odds ratio in female = 1.01; 95% CI 0.99–1.02, p = 0.38).

Conclusions
HOMA-IR was independently associated with CKD among men with MetS but not in women.