bluuebunny/crossref_metadata_2025 huggingface dataset:
LncRNA ZEB1-AS1 regulates hepatocellular carcinoma progression by targeting miR-23c
Authors: Xue Shuai , Lu Fengqin , Sun Chunhui , Zhao Jingjing , Zhen Honghua , Li Xin
Published: April 2021

Background

It has been reported that long-chain non-coding RNA (lncRNA) zinc finger E-box binding homeobox 1 antisense 1 (ZEB1-AS1) is an oncogene in various cancers, including hepatocellular carcinoma (HCC). We investigated the role and mechanism of ZEB1-AS1 as a competitive endogenous RNA (ceRNA) combined with miR-23c in HCC cell proliferation and invasion.

Methods

QRT-PCR was used to detect ZEB1-AS1 and miR-23c expressions in HCC tissues and cells. The dual luciferase reporter assay detected the targeted regulation of miR-23c and ZEB1-AS1. We also performed the correlation analysis of their expression in HCC tissues by the Spearman’s correlation analysis. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect the proliferation of hepatoma cells. Cell invasion was assessed by the Transwell assay.

Results

QRT-PCR results indicated ZEB1-AS1 was upregulated and miR-23c was downregulated in HCC tissues and cell lines. ZEB1-AS1 knockdown hampered the proliferation and invasion of HCC cells. Dual luciferase reporter assay showed that miR-23c is a target of ZEB1-AS1, and ZEB1-AS1 was significantly negatively correlated with the miR-23c expression in HCC tissues. The results of MTT and Transwell assay showed that miR-23c inhibition restored the inhibitory effect of ZEB1-AS1 knockdown on HCC cells proliferation and invasion.

Conclusions

As a ceRNA, lncRNA ZEB1-AS1 may play a vital role in inhibiting HCC progression through miR-23c, which will provide new clues and theoretical basis for the HCC diagnosis and treatment.
Exposures to 2,4-Dichlorophenoxyacetic acid with or without endotoxin upregulate small cell lung cancer pathway
Authors: Kaur Geetika , Kumar B. V. Sunil , Singh Baljit , Sethi R. S.
Published: April 2021

Background

Pesticide residues in food and environment along with airborne contaminants such as endotoxins pose health risk. Although herbicide 2,4-Dichlorophenoxyacetic acid (2,4-D) has been associated with increased risk of lung cancers such as small cell lung cancer (SCLC) among agricultural workers, there are no data on the SCLC signaling pathway upon 2,4-D exposure without LPS or in combination with endotoxin.

Methods

We exposed Swiss albino mice (N = 48) orally to high (37mg kg-1) and low (18.5 mg kg-1) dosages of 2,4-D dissolved in corn oil for 90 days followed by E. coli lipopolysaccharide (LPS) or normal saline solution (80 μl/animal). Lung samples and broncho-alveolar fluid (BALF) were subjected to Total histological score (THS) and total leucocyte count (TLC) and differential leucocytes count (DLC) analyses, respectively. We used microarray and bioinformatics tools for transcriptomic analyses and differentially expressed genes were analyzed to predict the top canonical pathways followed by validation of selected genes by qRT-PCR and immunohistochemistry.

Results

Total histological score (THS) along with BALF analyses showed lung inflammation following long term dietary exposure to high or low doses of 2,4-D individually or in combination with LPS. Microarray analysis revealed exposure to high dose of 2,4-D without or with LPS upregulated 2178 and 2142 and downregulated 1965 and 1719 genes, respectively (p < 0.05; minimum cut off 1.5 log fold change). The low dose without or with LPS upregulated 2133 and 2054 and downregulated 1838 and 1625 genes, respectively. Bioinformatics analysis showed SCLC as topmost dysregulated pathway along with differential expression of Itgb1, NF-κB1, p53, Cdk6 and Apaf1. Immunohistological and quantitative real time PCR (qRT-PCR) analyses also supported the transcriptomic data.

Conclusions

Taken together, the data show exposures to high and low dose of 2,4-D with/without LPS induced lung inflammation and altered pulmonary transcriptome profile with the involvement of the SCLC pathway. The data from the study provide the insights of the potential damage on lungs caused by 2,4-D and help to better understand the mechanism of this complex relation.
Impact of COVID-19 pandemic lockdown on exclusive breastfeeding in non-infected mothers
Authors: Latorre Giuseppe , Martinelli Domenico , Guida Pietro , Masi Ester , De Benedictis Roberta , Maggio Luca
Published: April 2021

Background

The COVID-19 pandemic has posed several challenges to the provision of newborn nutrition and care interventions including maternal support, breastfeeding and family participatory care. Italy was the first country to be exposed to SARS-CoV-2 in Europe. One of the measures adopted by the Italian government during COVID-19 pandemic was the total lockdown of the cities with complete confinement at home. We aimed to examine the impact of the lockdown caused by COVID-19 pandemic on exclusive breastfeeding in non-infected mothers.

Methods

We prospectively enrolled 204 mother-baby dyads during lockdown (9 March to 8 May 2020) that we compared to previously studied 306 mother-baby dyads admitted during the year 2018. To reduce the possible effect of confounding factors on exclusive breastfeeding, a 1:1 matching was performed by using an automatized procedure of stratification that paired 173 mother-baby dyads. Feeding modality was collected at discharge, 30 and 90 days of newborn’s life. Exclusive breastfeeding was considered when the infant received only breast milk and no other liquids or solids were given with the exception of vitamins, minerals or medicines.

Results

At discharge 69.4% of infants were exclusively breastfed during lockdown versus 97.7% of control group, 54.3% at 30 days vs 76.3 and 31.8% vs 70.5% at 90 days (p < 0.001). The proportion of breastfeeding remaining exclusive from discharge to 30-day was similar between groups (about 80%), but it was lower in lockdown group than in control cohort (58.5% vs 92.4%, p < 0.001) from 30- to 90-days.

Conclusions

Lockdown and home confinement led to a decrease of exclusively breastfeeding in the studied population. Considering the timing to shift from exclusive to non-exclusive breastfeeding, differences between study groups were concentrated during hospital stay and from 30- to 90 days of a newborn’s life, confirming that the hospital stay period is crucial in continuing exclusive breastfeeding at least for the first 30 days, but no longer relevant at 90 days of life.
Combination of long- and short-axis alar sacroplasty techniques under fluoroscopic guidance for osteoporotic sacral insufficiency fracture
Authors: Kao Feng-Chen , Hsu Yao-Chun , Chen Tzu-Shan , Liu Pao-Hsin , Tu Yuan-Kun
Published: April 2021

Background

Sacral insufficiency fracture (SIF) is rarer than osteoporotic vertebral compression fracture that occurs at other levels of the thoracolumbar spine. Percutaneous sacroplasty can effectively relieve pain and improve mobility. Several sacroplasty-based techniques have been reported to date.

Sacroplasty is often performed with computed tomography-guided cannula placement, which is time intensive and results in greater radiation exposure than that resulting from fluoroscopy. Herein, we report our preliminary experience with a combination of long- and short-axis alar sacroplasty techniques under fluoroscopic guidance for osteoporotic SIFs.

Methods

We retrospectively reviewed 44 consecutive patients with symptomatic osteoporotic SIFs who underwent alar sacroplasty between January 2013 and February 2020. The study group comprised 19 patients who underwent a combination of long- and short-axis alar sacroplasty techniques under fluoroscopic guidance. The control group comprised the remaining 25 patients who underwent short-axis alar sacroplasty under fluoroscopic guidance. Visual analog scale (VAS) scores, operation times, injected cement volumes, and postoperative complications were recorded.

Results

The VAS score for pain decreased in both groups; however, no significant difference was noted between the study and control groups in injected cement volume (3.55 ± 0.96 vs 2.94 ± 0.89 mL). The operation time was longer in the study group than in the control group (32 ± 7.1 vs 28.04 ± 4.99 min; P = 0.046). No major complications were noted.

Conclusion

A combination of long- and short-axis alar sacroplasty techniques can be effectively performed under fluoroscopic guidance for osteoporotic SIFs.
Aortic valve surgery for aortic regurgitation caused by Libman-Sacks endocarditis in a patient with primary antiphospholipid syndrome: a case report
Authors: Le Ho Yan , Ahmad Zaidi Nurul Atiqah , Salleh Ahmadi , Abdul Kareem Basheer Ahamed
Published: April 2021

Background

Antiphospholipid syndrome is an antibody mediated pro-thrombotic state leading to various arterial and venous thromboses. The syndrome can be either primary or secondary to other autoimmune diseases, commonly systemic lupus erythematosus. Cardiac involvement, in particular valvular disease is common in patients with antiphospholipid syndrome, occurring in about a third of these patients. Valvular diseases associated with antiphospholipid syndrome often occur as valve thickening and non-bacterial vegetation or Libman-Sacks endocarditis. Deposits of antiphospholipid immunoglobulin and complement components are commonly observed in the affected valves, suggesting an inflammatory process resulting in valvular vegetation and thickening. Libman-Sacks endocarditis has a high propensity towards mitral valve, although haemodynamically significant valvular dysfunction is rare.

Case presentation

We present a successful aortic valve replacement with cardiopulmonary bypass in a 48 years old lady with antiphospholipid syndrome, who has severe aortic regurgitation as a result of Libman-sacks endocarditis. Antiphospholipid antibodies were positive and the clinical data showed both negative cultures and infective parameters. Surgically resected vegetations revealed sterile fibrinous and verrucous vegetations on aortic valve. Valve replacement and the course of cardiopulmonary bypass was uneventful, and the patient was discharged well.

Conclusions

Classically Libman-Sacks endocarditis is often and more commonly associated with autoimmune diseases such as systemic lupus erythematosus, although it can occur in both primary and secondary antiphospholipid syndrome. It is not a common entity, and it is a frequent underestimated disease as most clinicians do not routinely screen for valvular lesion in patients with antiphospholipid syndrome unless they are symptomatic. However, due to its high prevalence of cardiac involvement, clinicians should have a high index of suspicion in the attempt to minimize cardiovascular and haemodynamic complications. Valve surgery in patients with antiphospholipid syndrome carries considerable early and late morbidity and mortality, usually caused by thromboembolic and bleeding events. The perioperative anticoagulation management and haemostatic aspect of antiphospholipid syndrome present an exceptional challenges to clinicians, surgeons, anaesthetists and laboratory personnel.
Short-term assessment of radial artery grafts with multidetector computed tomography
Authors: Qiao En , Wang Yuetang , Yu Jun , Wang Xu , Luo Xinjin , Wang Wei
Published: April 2021

Background

The clinical use of the radial artery (RA) in coronary artery bypass grafting (CABG) is still limited worldwide, although it has been recommended by several guidelines. Multidetector computed tomography (MDCT) is widely used to evaluate graft patency, as invasive coronary angiography could cause potentially serious risks including bleeding, dissection and stroke. This study aims to report the short-term results of the RA in CABG with MDCT.

Methods

The study population consists of 41 consecutive patients undergoing elective CABG with the RA graft between 2017 to 2018, with MDCT performed to evaluate graft patency during follow-up, and target vessels for the RA were non-left anterior descending coronary arteries with > 70% stenosis.

Results

A total of 150 grafts were assessed by MDCT during follow-up (mean, 8.9 ± 5.1 months). MDCT could clearly show the structure and patency of grafts, even for complex coronary artery revascularization. Graft patency of the left internal mammary artery was 92.9% (39/42), with the RA patency of 84.4% (38/45) and the patency of the saphenous vein graft of 81.1% (30/37). And the RA anastomosed to the left coronary artery system might have better patency than the RA anastomosed to the right coronary artery system (25/29, 86.2% vs 13/16, 81.3%, p = 0.686).

Conclusions

The short-term patency rate of RA grafts is good, and the RA might be associated with better patency when anastomosed to the left but not the right coronary artery. MDCT could provide excellent visualization of grafts in CABG.
Classification of endonasal HHT lesions using digital microscopy
Authors: Haubner F. , Schneider A. , Schinke H. , Bertlich M. , Weiss B. G. , Canis M. , Kashani F.
Published: April 2021

Background

Recurrent spontaneous epistaxis is the most common clinical manifestation and the most debilitating symptom in hereditary haemorrhagic telangiectasia (HHT) patients. To this date, there exist only a classification of HHT patients by different genetic mutations. There is no standard classification for the mucocutaneous endonasal manifestations of HHT. The aim of the present study was to document the variety of endonasal HHT lesions using digital microscopy and to propose a clinical classification.

Methods

We recorded the endonasal HHT lesions of 28 patients using a digital microscope. We reconstructed the 3D images und videos recorded by digital microscope afterwards and classified the endonasal lesions of HHT in two classes: Grade A, presence of only flat telangiectasias in the mucosa level and Grade B, (additional) presence of raised berry or wart-like telangiectasia spots. We investigated also Haemoglobin level by routine laboratory procedures, plasma VEGF level by ELISA, Severity of epistaxis by epistaxis severity score (ESS) and quality of life by a linear visual analogue scale (VAS).

Results

We found a higher quality of life and a lower severity of epistaxis in Grade A patients in comparison to Grade B patients. No difference in plasma VEGF level and in Haemoglobin between Grad A patients and Grade B patients could be detected. Plasma VEGF levels showed no gender specific differences. It could also not be correlated to the extranasal manifestation.

Conclusion

The classification for endonasal manifestation of HHT proposed in this study indicates severity of epistaxis und quality of life. Digital microscopy with the ability of 3D reconstruction of images presents a useful tool for such classifications. The classification of endonasal HHT lesions using digital microscopy allows to evaluate the dynamic of HHT lesions in the course of time independent of examiner. This allows also to evaluate the efficacy of the different treatment modalities by dynamic of HHT lesions. Moreover digital microscopy is very beneficial in academic teaching of rare diseases.
Immunophenotypic characterization of TCR γδ T cells and MAIT cells in HIV-infected individuals developing Hodgkin’s lymphoma
Authors:   the Swiss HIV Cohort Study, Muller Christina K. S. , Spagnuolo Julian , Audigé Annette , Chancellor Andrew , Russenberger Doris , Scherrer Alexandra U. , Hoffmann Matthias , Kouyos Roger , Battegay Manuel , De Libero Gennaro , Speck Roberto F.
Published: April 2021

Background

Despite successful combined antiretroviral therapy (cART), the risk of non-AIDS defining cancers (NADCs) remains higher for HIV-infected individuals than the general population. The reason for this increase is highly disputed. Here, we hypothesized that T-cell receptor (TCR) γδ cells and/or mucosal-associated invariant T (MAIT) cells might be associated with the increased risk of NADCs. γδ T cells and MAIT cells both serve as a link between the adaptive and the innate immune system, and also to exert direct anti-viral and anti-tumor activity.

Methods

We performed a longitudinal phenotypic characterization of TCR γδ cells and MAIT cells in HIV-infected individuals developing Hodgkin’s lymphoma (HL), the most common type of NADCs. Cryopreserved PBMCs of HIV-infected individuals developing HL, matched HIV-infected controls without (w/o) HL and healthy controls were used for immunophenotyping by polychromatic flow cytometry, including markers for activation, exhaustion and chemokine receptors.

Results

We identified significant differences in the CD4+ T cell count between HIV-infected individuals developing HL and HIV-infected matched controls within 1 year before cancer diagnosis. We observed substantial differences in the cellular phenotype mainly between healthy controls and HIV infection irrespective of HL. A number of markers tended to be different in Vδ1 and MAIT cells in HIV+HL+ patients vs. HIV+ w/o HL patients; notably, we observed significant differences for the expression of CCR5, CCR6 and CD16 between these two groups of HIV+ patients.

Conclusion

TCR Vδ1 and MAIT cells in HIV-infected individuals developing HL show subtle phenotypical differences as compared to the ones in HIV-infected controls, which may go along with functional impairment and thereby may be less efficient in detecting and eliminating malignant cells. Further, our results support the potential of longitudinal CD4+ T cell count analysis for the identification of patients at higher risk to develop HL.
‘We need someone to deliver our voices’: reflections from conducting remote qualitative research in Syria
Authors: Douedari Yazan , Alhaffar Mervat , Duclos Diane , Al-Twaish Mohamed , Jabbour Samer , Howard Natasha
Published: April 2021

The need to generate evidence in spaces considered insecure and inhabited by potentially extremely vulnerable individuals (e.g. conflict-affected people who may not have means to move) has led researchers to study conflict-affected settings remotely. Increased attention to remote research approaches from social scientists, due to COVID-19-related travel restrictions, is sparking interest on appropriate methods and tools. Drawing on several years’ experience of remotely conducting qualitative research in Syria, we discuss challenges and approaches to conducting more inclusive, participatory, and meaningful research from a distance. The logistics, ethics, and politics of conducting research remotely are symptomatic of broader challenges in relation to the decolonisation of global and humanitarian health research. Key to the success of remote approaches is the quality of the relationships researchers need to be able to develop with study participants without face-to-face interactions and with limited engagement ‘in the field’. Particularly given overdue efforts to decolonise research institutions and methods, lead researchers should have a meaningful connection with the area in which they are conducting research. This is critical both to reduce chances that it will be extractive and exploitative and additionally for the quality of interpretation.
Alginate-chitosan core-shell microcapsule cultures of hepatic cells in a small scale stirred bioreactor: impact of shear forces and microcapsule core composition
Authors: Khodabakhshaghdam Shahla , Khoshfetrat Ali Baradar , Rahbarghazi Reza
Published: April 2021

A small scale stirred bioreactor was designed and the effect of different agitation rates (30, 60 and 100 rpm) was investigated on HepG2 cells cultured in alginate-chitosan (AC) core-shell microcapsule in terms of the cell proliferation and liver-specific function. The microencapsulated hepatic cells could proliferate well when they were cultured for 10 days at 30 rpm while the cell-laden microcapsules showed no cell proliferation at 100 rpm in the bioreactor system. Albumin production rate, as an important liver function, increased also 1.8- and 1.5- fold under stirring rate of 30 rpm compared to the static culture and 60 rpm of agitation, respectively. Moreover, In comparison with the static culture, about 1.5-fold increment in urea production was observed at 30 rpm. Similarly, the highest expressions of albumin and P450 genes were found at 30 rpm stirring rate, which were 4.9- and 19.2-fold of the static culture. Addition of collagen to the microcapsule core composition (ACol/C) could improve the cell proliferation and functionality at 60 rpm in comparison with the cell-laden microcapsules without collagen. The study demonstrated the hepatic cell-laden ACol/C microcapsule hydrogel cultured in the small scale stirred bioreactor at low mixing rate has a great potential for mass production of the hepatic cells while maintaining liver-specific functions.
Association between menopausal hormone therapy, mammographic density and breast cancer risk: results from the E3N cohort study
Authors: Fornili M. , Perduca V. , Fournier A. , Jérolon A. , Boutron-Ruault M. C. , Maskarinec G. , Severi G. , Baglietto L.
Published: April 2021

Background

Menopausal hormone therapy (MHT) is a risk factor for breast cancer (BC). Evidence suggests that its effect on BC risk could be partly mediated by mammographic density. The aim of this study was to investigate the relationship between MHT, mammographic density and BC risk using data from a prospective study.

Methods

We used data from a case-control study nested within the French cohort E3N including 453 cases and 453 matched controls. Measures of mammographic density, history of MHT use during follow-up and information on potential confounders were available for all women. The association between MHT and mammographic density was evaluated by linear regression models. We applied mediation modelling techniques to estimate, under the hypothesis of a causal model, the proportion of the effect of MHT on BC risk mediated by percent mammographic density (PMD) for BC overall and by hormone receptor status.

Results

Among MHT users, 4.2% used exclusively oestrogen alone compared with 68.3% who used exclusively oestrogens plus progestogens. Mammographic density was higher in current users (for a 60-year-old woman, mean PMD 33%; 95% CI 31 to 35%) than in past (29%; 27 to 31%) and never users (24%; 22 to 26%). No statistically significant association was observed between duration of MHT and mammographic density. In past MHT users, mammographic density was negatively associated with time since last use; values similar to those of never users were observed in women who had stopped MHT at least 8 years earlier. The odds ratio of BC for current versus never MHT users, adjusted for age, year of birth, menopausal status at baseline and BMI, was 1.67 (95% CI, 1.04 to 2.68). The proportion of effect mediated by PMD was 34% for any BC and became 48% when the correlation between BMI and PMD was accounted for. These effects were limited to hormone receptor-positive BC.

Conclusions

Our results suggest that, under a causal model, nearly half of the effect of MHT on hormone receptor-positive BC risk is mediated by mammographic density, which appears to be modified by MHT for up to 8 years after MHT termination.
ΔNp63 is a pioneer factor that binds inaccessible chromatin and elicits chromatin remodeling
Authors: Yu Xinyang , Singh Prashant K. , Tabrejee Shamira , Sinha Satrajit , Buck Michael J.
Published: April 2021

Background

ΔNp63 is a master transcriptional regulator playing critical roles in epidermal development and other cellular processes. Recent studies suggest that ΔNp63 functions as a pioneer factor that can target its binding sites within inaccessible chromatin and induce chromatin remodeling.

Methods

In order to examine if ΔNp63 can bind to inaccessible chromatin and to determine if specific histone modifications are required for binding, we induced ΔNp63 expression in two p63-naïve cell lines. ΔNp63 binding was then examined by ChIP-seq and the chromatin at ΔNp63 targets sites was examined before and after binding. Further analysis with competitive nucleosome binding assays was used to determine how ΔNp63 directly interacts with nucleosomes.

Results

Our results show that before ΔNp63 binding, targeted sites lack histone modifications, indicating ΔNp63’s capability to bind at unmodified chromatin. Moreover, the majority of the sites that are bound by ectopic ΔNp63 expression exist in an inaccessible state. Once bound, ΔNp63 induces acetylation of the histone and the repositioning of nucleosomes at its binding sites. Further analysis with competitive nucleosome binding assays reveal that ΔNp63 can bind directly to nucleosome edges with significant binding inhibition occurring within 50 bp of the nucleosome dyad.

Conclusion

Overall, our results demonstrate that ΔNp63 is a pioneer factor that binds nucleosome edges at inaccessible and unmodified chromatin sites and induces histone acetylation and nucleosome repositioning.
Antibiotic susceptibility and genetic relatedness of Shigella species isolated from food and human stool samples in Qazvin, Iran
Authors: Pakbin Babak , Didban Abdollah , Monfared Yousef Khazaye , Mahmoudi Razzagh , Peymani Amir , Modabber Mohammad Reza
Published: April 2021

Objective

The aim of this study was to investigate the genetic relatedness and antimicrobial resistance among Shigella species isolated from food and stool samples. Using cross sectional study method, Shigella spp. were isolated from food and clinical samples using culture-based, biochemical and serological methods. Antimicrobial susceptibility and genetic relatedness among the isolates were evaluated using disk diffusion and RAPD-PCR methods respectively.

Results

The prevalence of Shigella spp. were 4.84 and 7.7% in food and stool samples respectively. All food isolates were Sh. sonnei. 91.42% of the Shigella stool isolates were Sh. sonnei. 62.5% of food isolates were resistant to tetracycline. 46.8, 50 and 65.8% of clinical isolates were resistant to imipenem, amikacin and azithromycin respectively. 50 and 85.7% of the food and clinical isolates respectively were MDR. Dendrogram generated by RAPD-PCR showed that the isolates from food and stool samples were categorized in a same group. Close genetic relatedness between MDR Shigella isolates from food and clinical samples indicate that foods can be considered as one of the main vehicles for transmission of MDR Shigella to human causing acute diseases. Survey of MDR Shigella among food and clinical samples is strongly suggested to be implemented.
Effects of an intensive lifestyle intervention and the role of sleep in people living with HIV and prediabetes: a pilot and feasibility study
Authors: Nimitphong Hataikarn , Sungkanuparph Somnuek , Areevut Chatvara , Saetung Sunee , Jerawatana Ratanaporn , Hathaidechadusadee Amornrat , Somwang Supaporn , Tongchom Wanabhorn , Saibuathong Nampeth , Sakmanarit Jandanee , Pichitchaipitak Orawan , Phuphuakrat Angsana , Reutrakul Sirimon
Published: April 2021

Objectives

Prediabetes is prevalent in people living with HIV (PLWH). Insufficient and irregular sleep are linked to abnormal glucose metabolism. This study aimed to investigate the differences in sleep characteristics between PLWH with and without prediabetes, determine the acceptability/feasibility and effects of a pilot six-month intensive lifestyle intervention (ILI) program on glucose metabolism in those with prediabetes, and determine how sleep modulates these effects.

Results

Thirty-nine PLWH (20 normoglycemia and 19 prediabetes) participated. There were no differences in sleep characteristics between individuals with normoglycemia and prediabetes. Next, thirteen individuals with prediabetes completed a six-month ILI program. The ILI program resulted in significant body weight reduction at 6 months (63.5 ± 13.9 to 61.9 ± 14.0 kg,p = 0.012), which was maintained at 12 months (p < 0.001). Waist circumferences were significantly decreased at 12 months (85.4 ± 11.7 to 82.9 ± 12.7 cm,p = 0.014). An increase in sleep variability was significantly associated with an increase in 2-h plasma glucose, independent of changes in BMI (b = 0.603), and physical activity (b = 0.774). This pilot study suggested that ILI in PLWH with prediabetes is feasible and effective in improving metabolic control, with its effects possibly modulated by sleep variability. These findings should be confirmed in a larger study to reduce diabetes risk in this population.

Trail registration:ClinicalTrial.gov, NCT03545217 (date of registration: May 22, 2018)
Disease-associated DNA methylation signatures in esophageal biopsies of children diagnosed with Eosinophilic Esophagitis
Authors: Strisciuglio Caterina , Payne Felicity , Nayak Komal , Andreozzi Marialuisa , Vitale Alessandra , Miele Erasmo , Zilbauer Matthias
Published: April 2021

Eosinophilic esophagitis (EoE) is a leading cause of dysphagia and food impaction in children and adults. The diagnosis relies on histological examination of esophageal mucosal biopsies and requires the presence of > 15 eosinophils per high-powered field. Potential pitfalls include the impact of biopsy sectioning as well as regional variations of eosinophil density. We performed genome-wide DNA methylation analyses on 30 esophageal biopsies obtained from children diagnosed with EoE (n = 7) and matched controls (n = 13) at the time of diagnosis as well as following first-line treatment. Analyses revealed striking disease-associated differences in mucosal DNA methylation profiles in children diagnosed with EoE, highlighting the potential for these epigenetic signatures to be developed into clinically applicable biomarkers.
A randomized, double-blind, phase 2b proof-of-concept clinical trial in early Alzheimer’s disease with lecanemab, an anti-Aβ protofibril antibody
Authors: Swanson Chad J. , Zhang Yong , Dhadda Shobha , Wang Jinping , Kaplow June , Lai Robert Y. K. , Lannfelt Lars , Bradley Heather , Rabe Martin , Koyama Akihiko , Reyderman Larisa , Berry Donald A. , Berry Scott , Gordon Robert , Kramer Lynn D. , Cummings Jeffrey L.
Published: April 2021

Background

Lecanemab (BAN2401), an IgG1 monoclonal antibody, preferentially targets soluble aggregated amyloid beta (Aβ), with activity across oligomers, protofibrils, and insoluble fibrils. BAN2401-G000-201, a randomized double-blind clinical trial, utilized a Bayesian design with response-adaptive randomization to assess 3 doses across 2 regimens of lecanemab versus placebo in early Alzheimer’s disease, mild cognitive impairment due to Alzheimer’s disease (AD) and mild AD dementia.

Methods

BAN2401-G000-201 aimed to establish the effective dose 90% (ED90), defined as the simplest dose that achieves ≥90% of the maximum treatment effect. The primary endpoint was Bayesian analysis of 12-month clinical change on the Alzheimer’s Disease Composite Score (ADCOMS) for the ED90 dose, which required an 80% probability of ≥25% clinical reduction in decline versus placebo. Key secondary endpoints included 18-month Bayesian and frequentist analyses of brain amyloid reduction using positron emission tomography; clinical decline on ADCOMS, Clinical Dementia Rating-Sum-of-Boxes (CDR-SB), and Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog14); changes in CSF core biomarkers; and total hippocampal volume (HV) using volumetric magnetic resonance imaging.

Results

A total of 854 randomized subjects were treated (lecanemab, 609; placebo, 245). At 12 months, the 10-mg/kg biweekly ED90 dose showed a 64% probability to be better than placebo by 25% on ADCOMS, which missed the 80% threshold for the primary outcome. At 18 months, 10-mg/kg biweekly lecanemab reduced brain amyloid (−0.306 SUVr units) while showing a drug-placebo difference in favor of active treatment by 27% and 30% on ADCOMS, 56% and 47% on ADAS-Cog14, and 33% and 26% on CDR-SB versus placebo according to Bayesian and frequentist analyses, respectively. CSF biomarkers were supportive of a treatment effect. Lecanemab was well-tolerated with 9.9% incidence of amyloid-related imaging abnormalities-edema/effusion at 10 mg/kg biweekly.

Conclusions

BAN2401-G000-201 did not meet the 12-month primary endpoint. However, prespecified 18-month Bayesian and frequentist analyses demonstrated reduction in brain amyloid accompanied by a consistent reduction of clinical decline across several clinical and biomarker endpoints. A phase 3 study (Clarity AD) in early Alzheimer’s disease is underway.

Trial registration

ClinicalTrials.govNCT01767311.
Interleukin-35 inhibited the production of histamine and pro-inflammatory cytokines through suppression MAPKs pathway in HMC-1 cells
Authors: Fu Li-xin , Chen Tao , Sun Qiao-mei , Zhou Pei-mei , Guo Zai-pei
Published: April 2021

Background

IL-35 is a newly anti-inflammatory cytokine that belongs to the IL-12 family. Mast cells, as one of the major effector cells in the immune response system, plays an important role in the pathogenesis of chronic spontaneous urticarial (CSU). Our study aims to explore the inhibited role of IL-35 in HMC-1.

Methods

The effects of IL-35 on cell proliferation, cytokine expression, and histamine release in a human mast cell line (HMC­1) were investigated by CCK8, ELISA, or RT-PCR. The phosphorylation levels of ERK1/2, p38, and JNK1/2, in PMA plus A23187 induced HMC-1 cells was detected by Western Blot.

Results

We found that IL-35 significantly inhibited the proliferation of HMC-1 cells stimulated by PMA and A23187. IL-35 also down-regulates the release of histamine and the mRNA expression of IL-6 and IL-17 in activated HMC-1. Furthermore, IL-35 markedly inhibited the phosphorylation levels of ERK1/2, p38, and JNK1/2, in PMA plus A23187 induced HMC-1 cells.

Conclusions

This study provides the first observations on the inhibitory and anti-inflammatory effect of IL-35 in activated HMC-1 cells. We suggest that IL35 may play an inhibited role in the pathogenesis of CSU.
Sarcoidosis with marked necrosis in enlarged lymph nodes mimics mycobacterial infection: a case report
Authors: Miyashita Yosuke , Hara Munechika , Iwakami Shin-ichiro , Matsuda Hironari , Iwakami Naoko , Takahashi Kazuhisa
Published: April 2021

Background

Sarcoidosis is pathologically characterized by the formation of non-necrotizing epithelioid cell granulomas. However, pathological findings of patients with sarcoidosis have rarely revealed necrosis. We report here on a patient with sarcoidosis which needed to be distinguished from infectious disease because of marked necrosis in the lymph nodes.

Case presentation

A 46-year-old Japanese woman was referred to our hospital due to a dry cough and appetite loss. A chest X-ray and computed tomography revealed markedly enlarged mediastinal and hilar lymph nodes and hepatosplenomegaly. Surgical biopsy of these lymph nodes was performed in order to make a diagnosis. Pathological findings revealed epithelioid cell granuloma with marked necrosis that suggested infectious etiology such as mycobacterial and fungal infections. In addition to the pathological findings, immunoglobulin A (IgA) antibody for Mycobacterium avium complex (MAC), enlargement of lymph nodes and hepatosplenomegaly indicated disseminated MAC, while sarcoidosis was considered as another important differential diagnosis according to elevated angiotensin-converting enzyme, soluble interleukin-2 receptor and uveitis. While waiting for the results of the cultures of acid-fast bacilli, the symptoms of cough and consumption had worsened, and initiation of therapy was required before the confirmed diagnosis. The therapy for MAC was initiated because it was feared that immunosuppressive therapy containing corticosteroid for sarcoidosis could worsen the patient’s condition if MAC infection was the main etiology. However, the treatment for MAC was not effective, and it was clarified that no acid-fast bacilli were cultured in the liquid culture medium, so the diagnosis was corrected to sarcoidosis after reconsideration of clinical and pathological findings. Prednisolone (30 mg/day) was administered orally, and the patient’s symptoms and radiological findings improved.

Conclusion

Sarcoidosis must be considered even if pathological findings reveal marked necrosis, because rare cases of sarcoidosis exhibit extensive necrosis in lymph nodes. It is extremely important to carefully examine the clinical and pathological findings through discussion with the examining pathologist to reach the correct diagnosis.
Exploring the challenges and features of implementing performance-based payment plan in hospitals: a protocol for a systematic review
Authors: Mousaloo Asieh , Amir-Behghadami Mehrdad , Janati Ali , Gholizadeh Masoumeh
Published: April 2021

Background

Implementing performance-based payment (PBP) plan has led to developing a number of significant potentialities such as performance improvement and effectiveness, quality improvement of provided services, and decline in health system expenditure in hospitals. Despite the fact that PBP plan has a variety of potential advantages, its implementation still may face some challenges. Hence, it seems crucial to identify these barriers and challenges in order to devise some strategies and interventions to pave the way for better implementation of PBP in hospitals. The aim of this proposed protocol is to identify, summarize, and synthesize the existing evidence by undertaking a systematic review to explore the challenges, barriers, and features of implementing PBP in hospitals.

Methods and analysis

An inclusive search of the literature will be conducted in seven international and national databases including PubMed/MEDLINE, Scopus, Cochrane Library and Web of Science, Magiran, Scientific Information Database (SID), and Barakat knowledge network system (BKNS). The search will be limited to the studies published in English or Persian language. Database search will be supplemented by hand-search of citation, reference lists, and grey literature sources. Based on the pre-established criteria in all steps of the review, two researchers will independently screen all of the retrieved studies. Any discrepancies will be resolved through a discussion between two researchers. In cases where consensus is not reached, it will be referred to a third researcher. The methodological quality of all the included studies will be appraised using the Mixed Methods Appraisal Tool (MMAT). The data will be extracted by means of using a data extraction form, which will be developed and piloted by the research team. The findings will be synthesized through directed content analysis method.

Discussion

With the growth and development of payment systems all over the world, it is expected that recognizing the challenges of implementing a PBP plan in hospitals will be useful in developing and designing strategies to better implement this plan.

Systematic review registration

PROSPERO registration number CRD42020152569
On a nonlocal problem for parabolic equation with time dependent coefficients
Authors: Phuong Nguyen Duc , Binh Ho Duy , Long Le Dinh , Yen Dang Van
Published: April 2021

This paper is devoted to the study of existence and uniqueness of a mild solution for a parabolic equation with conformable derivative. The nonlocal problem for parabolic equations appears in many various applications, such as physics, biology. The first part of this paper is to consider the well-posedness and regularity of the mild solution. The second one is to investigate the existence by using Banach fixed point theory.
The politicians’ perspectives on participation in mammographic screening: an interview-based study from a region in Sweden
Authors: Norfjord van Zyl Maria , Tillgren Per , Asp Margareta
Published: April 2021

Background

Breast cancer is the most common cancer type among women globally. To facilitate early detection, all 40–74-year-old female residents of Sweden are invited to participate in a population-based mammographic screening programme. Approximately 20% of all invited women decline the offer, and if this is due to systematic differences that can be adjusted, it can indicate inequity in healthcare. Assessment of and being updated about the health and healthcare of the residents are largely the responsibilities of the self-governed regions in Sweden. The understanding of the residents’ health serves as a basis for decision making and priority setting. This study aims to describe how politicians representing a region in Sweden perceive women’s participation in mammographic screening and the politicians’ own possibility to promote such participation.

Methods

Qualitative thematic analysis was conducted on the data obtained from individual semi-structured interviews held in 2019. The interviewees comprised ten politicians (six women and four men, 38–71 years old) representing a sub-committee focusing on public health and healthcare issues.

Results

Two main themes have been identified: 1) expected actions and 2) expected conditions for acting, including a total of four sub-themes. According to the politicians, the expected actions, such as obtaining information and being updated about matters regarding mammographic screening, concern both the women invited to the screening and the politicians themselves. Additionally, for both the individual and the healthcare organisation, here represented by the politicians, expected actions entail a shared commitment to maintain health. The expected conditions for acting refer to the politician’s awareness of the factors influencing the women’s decision to undergo or refuse the screening and having the resources to enable taking actions to facilitate participation.

Conclusions

Expected actions and expected conditions for acting are tightly connected and entail some form of prioritisation by the politicians. Setting the priorities can be based on information about the purpose of the screening and an understanding of social determinants’ impacts on women’s decision to refrain from mammographic screening, as well as available resources.
Lower pattern recognition memory scores in anorexia nervosa
Authors: Keeler Johanna , Lambert Ellen , Olivola Miriam , Owen Judith , Xia Jingjing , Thuret Sandrine , Himmerich Hubertus , Cardi Valentina , Treasure Janet
Published: April 2021

Background

There is extensive evidence for volumetric reductions in the hippocampus in patients with anorexia nervosa (AN), however the impact on function is unclear. Pattern separation and recognition are hippocampus-dependent forms of learning thought to underlie stimulus discrimination.

Methods

The present study used the Mnemonic Similarity Task to investigate pattern separation and recognition for the first time in patients with AN (N = 46) and healthy controls (N = 56). An Analysis of Covariance examined between-group differences, controlling for age, antidepressant use and method of task delivery (remote vs. in person).

Results

When controlling for covariates, pattern recognition memory scores were lower in the AN group with a medium effect size (d = 0.51). In contrast, there was a small effect whereby patients with AN had a greater pattern separation score than controls (d = 0.34), albeit this difference was not significant at the p = 0.05 threshold (p = 0.133). Furthermore, pattern separation and recognition memory abilities were not related to age, body mass index, eating disorder psychopathology or trait anxiety levels.

Conclusions

This preliminary study provides initial evidence for an imbalance in pattern separation and recognition abilities in AN, a hippocampus-dependent cognitive ability. Further studies should endeavour to investigate pattern separation and recognition performance further in AN, as well as investigate other hippocampus-dependent functions.
The role of personality traits, sociocultural factors, and body dissatisfaction in anorexia readiness syndrome in women
Authors: Rymarczyk Karolina
Published: April 2021

Background

The mass media promote certain standards of physical attractiveness. The media coverage, in interaction with body dissatisfaction and personality traits, may intensify specified behaviors in women, that should help them to obtain an ideal body image, e.g., excessive concentration on body image, weight control, increase in physical activity. The intensification of these behaviors can develop anorexia readiness syndrome (ARS) in women. The paper presents a study on the role of the Five-Factor Model personality traits (neuroticism, extraversion, agreeableness, conscientiousness, and intellect/openness), sociocultural factors (internalization, sociocultural pressure, information seeking), and body dissatisfaction in anorexia readiness syndrome.

Methods

The study involved 1533 Polish women aged 18–36 (M = 22.51, SD = 2.41). The participants completed the online version of the set of questionnaires. The link to the study was shared in social media groups. Personality dimensions were measured with the BFI, sociocultural factors were evaluated by means of the SATAQ-3, the degree of body dissatisfaction was assessed with the BIQ, while ARS was measured using five self-reported items referring to specific behaviors from TIAE.

Results

Hierarchical multiple regression analysis revealed internalization, sociocultural pressure, and body dissatisfaction as significant predictors of ARS. While neuroticism was correlated with ARS, it lost its predictive value after entering body dissatisfaction in the regression model.

Conclusions

The factors associated with ARS were (1) neuroticism among personality traits, (2) internalization and pressure from sociocultural norms among sociocultural attitudes, and (3) body dissatisfaction. The key finding is the absence of statistical significance for neuroticism in predicting ARS after including body dissatisfaction. In future research, the group of men and patients with anorexia nervosa can be included, and the age range can be extended to include younger people. The catalog of potential ARS predictors may be expanded, which can help to explain the role of neuroticism in ARS.
A pilot trial of repetitive transcranial magnetic stimulation of the dorsomedial prefrontal cortex in anorexia nervosa: resting fMRI correlates of response
Authors: Woodside D. Blake , Dunlop Katharine , Sathi Charlene , Lam Eileen , McDonald Brigitte , Downar Jonathan
Published: April 2021

Background

Patients with anorexia nervosa (AN) face severe and chronic illness with high mortality rates, despite our best currently available conventional treatments. Repetitive transcranial magnetic stimulation (rTMS) has shown increasing efficacy in treatment-refractory cases across a variety of psychiatric disorders comorbid with AN, including major depression, Obsessive Compulsive Disorder (OCD), and Post traumatic Stress Disorder (PTSD). However, to date few studies have examined the effects of a course of rTMS on AN pathology itself.

Methods

Nineteen patients with AN underwent a 20–30 session open-label course of dorsomedial prefrontal rTMS for comorbid Major Depressive Disorder (MDD) ± PTSD. Resting-state functional MRI was acquired at baseline in 16/19 patients.

Results

Following treatment, significant improvements were seen in core AN pathology on the EDE global scale, and to a lesser extent on the shape and weight concerns subscales. Significant improvements in comorbid anxiety, and to a lesser extent depression, also ensued. The greatest improvements were seen in patients with lower baseline functional connectivity from the dorsomedial prefrontal cortex (DMPFC) target to regions in the right frontal pole and left angular gyrus.

Conclusions

Despite the limited size of this preliminary, open-label study, the results suggest that rTMS is safe in AN, and may be useful in addressing some core domains of AN pathology. Other targets may also be worth studying in this population, in future sham-controlled trials with larger sample sizes.

Trial registration

Trial registration ClinicalTrials.gov NCT04409704.

Registered May 282,020. Retrospectively registered.