bluuebunny/crossref_metadata_2025_split huggingface dataset:
In-vitro Immunomodulatory activity of Azadirachta indica A.Juss. Ethanol: water mixture against HIV associated chronic CD4+ T-cell activation/ exhaustion
Authors: Olwenyi Omalla A. , Asingura Bannet , Naluyima Prossy , Anywar Godwin Upoki , Nalunga Justine , Nakabuye Mariam , Semwogerere Michael , Bagaya Bernard , Cham Fatim , Tindikahwa Allan , Kiweewa Francis , Lichter Eliezer Z. , Podany Anthony T. , Fletcher Courtney V. , Byrareddy Siddappa N. , Kibuuka Hannah 
Published: April 2021

Abstract
Background
In Sub-Saharan Africa, herbal therapy continues to be utilized for HIV-1 disease management. However, the therapeutic benefits of these substances remain ambiguous. To date, little is known about the effects of these plant extracts on chronic CD4 + T-cell activation and exhaustion which is partly driven by HIV-1 associated microbial translocation.

Methods
Effects of Azadirachta indica, Momordica foetida and Moringa oleifera ethanol: water mixtures on cell viability were evaluated using the Guava PCA system. Then, an in-vitro cell culture model was developed to mimic CD4+ T cell exposures to antigens following HIV-1 microbial translocation. In this, peripheral blood mononuclear cells (PBMCs) isolated from HIV negative (n = 13), viral load < 1000 copies per mL (n = 10) and viral load > 1000 copies per mL (n = 6) study participants from rural Uganda were treated with Staphylococcus enterotoxin B (SEB). Then, the candidate plant extract (A. indica) was added to test the potential to inhibit corresponding CD4+ T cell activation. Following BD Facs Canto II event acquisition, variations in %CD38, %CD69, Human Leukocyte Antigen -DR (HLA-DR), Programmed cell death protein 1 (PD-1), T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3), interferon gamma (IFN γ) and interleukin 2 (IL-2) CD4 + T cell expression were evaluated.

Results
Following exposure to SEB, only A. indica demonstrated a concentration-dependent ability to downregulate the levels of CD4 + T cell activation. At the final concentration of 0.500 μg/mL of A. indica, a significant downregulation of CD4 + CD38 + HLA-DR+ expression was observed in HIV negative (p < 0.0001) and both HIV infected groups (P = 0.0313). This plant extract also significantly lowered SEB induced % CD4+ T cell HLADR, PD-1 and Tim-3 levels. PD-1 and CD69 markers were only significantly downmodulated in only the HIV negative ((p = 0.0001 and p = 0.0078 respectively) and viral load< 1000 copies per ml (p = 0.0078) groups.

Conclusion
A. indica exhibited the in-vitro immunomodulatory potential to inhibit the continuum of SEB induced CD4+ T-cell activation/ exhaustion without impacting general T-cell specific functions such as cytokine secretion. Additional studies are needed to confirm A. indica as a source of natural products for targeting persistent immune activation and inflammation during ART.
Letter to the editor: Vitamin D levels in acute illness and clinical severity in COVID-19 patients
Authors: Lohia Prateek , Kapur Shweta , Patel Pragnesh , Seyoum Berhane 
Published: April 2021

AbstractWe would like to comment on the recently published article titled: “Circulating Vitamin D levels status and clinical prognostic indices in COVID-19 patients” by Ricci et al. The authors grouped the patients into two groups according to the vitamin D levels measured at the time of admission into the hospital and reported that lower vitamin D levels are associated with elevated D-dimer and IL-6 levels, low CD4/CD8 ratio and compromised clinical findings with elevated LIPI and SOFA scores. However, review of recent literature shows this association to be debatable. The 25-hydroxyvitamin D levels in the initial phase of critical illness have been reported to drop rapidly and hence consideration of the time of measurement from symptom onset would have enhanced the clinical relevance of these findings. Inferred association between vitamin D levels and disease severity based on SOFA score in COVID-19 patients, needs to be further explored in the light of the recent literature which casts doubt on using SOFA score at admission to predict mortality in COVID-19.
Literature-based considerations regarding organizing and performing cardiac surgery against the backdrop of the coronavirus pandemic
Authors: Juraszek Andrzej , Kuriata Jarosław , Kołsut Piotr , Hryniewiecki Tomasz , Różewicz-Juraszek Monika , Dziodzio Tomasz , Kuśmierczyk Mariusz 
Published: April 2021

Abstract
Background
The ongoing coronavirus disease 2019 (Covid-19) pandemic presents challenges for surgeons of all disciplines, including cardiologists. The volume of cardiac surgery cases has to comply with the mandatory constraints of healthcare capacities. The treatment of Covid-19-positive patients must also be considered. Unfortunately, no scientific evidence is available on this issue. Therefore, this study aimed to offer some consensus-based considerations, derived from available scientific papers, regarding the organization and performance of cardiac surgery against the backdrop of the Covid-19 pandemic.

Methods
Key recommendations were extracted from recent literature concerning cardiac surgery.
RESULTSː Reducing elective cardiac procedures should be based on frequent clinical assessment of patients on the waiting list (every one or two weeks) and the current local status of the Covid-19 pandemic. Screening tests at admission for every patient are broadly recommended. Where appropriate, alternative treatment methods can be considered, including percutaneous techniques and minimally invasive surgery, if performed by experienced cardiac surgery teams.

Conclusions
There is little evidence on the strategies to organize cardiac surgery in the Covid-19 pandemic. Most authors agree on reducing elective operations based on patients’ clinical condition and the status of the Covid-19 pandemic. Admission screenings and the use of percutaneous or minimally invasive approaches should be preferred to reduce in-hospital stays.
Comparison of the survival outcomes of laparoscopy versus laparotomy in treatment of early-stage ovarian cancer: a systematic review and meta-analysis
Authors: Kong Qingduo , Wei Hongyi , Zhang Jing , Li Yilin , Wang Yongjun 
Published: April 2021

Abstract
Background
Laparoscopy has been widely used for patients with early-stage epithelial ovarian cancer (eEOC). However, there is limited evidence regarding whether survival outcomes of laparoscopy are equivalent to those of laparotomy among patients with eEOC. The result of survival outcomes of laparoscopy is still controversial. The aim of this meta-analysis is to analyze the survival outcomes of laparoscopy versus laparotomy in the treatment of eEOC.

Methods
According to the keywords, Pubmed, Embase, Cochrane Library and Clinicaltrials.gov were searched for studies from January 1994 to January 2021. Studies comparing the efficacy and safety of laparoscopy versus laparotomy for patients with eEOC were assessed for eligibility. Only studies including outcomes of overall survival (OS) were enrolled. The meta-analysis was performed using Stata software (Version 12.0) and Review Manager (Version 5.2).

Results
A total of 6 retrospective non-random studies were included in this meta-analysis. The pooled results indicated that there was no difference between two approaches for patients with eEOC in OS (HR = 0.6, P = 0.446), progression-free survival (PFS) (HR = 0.6, P = 0.137) and upstaging rate (OR = 1.18, P = 0.54). But the recurrence rate of laparoscopic surgery was lower than that of laparotomic surgery (OR = 0.48, P = 0.008).

Conclusions
Laparoscopy and laparotomy appear to provide comparable overall survival and progression-free survival outcomes for patients with eEOC. Further high-quality studies are needed to enhance this statement.
Diabetes related distress is high in inpatients with diabetes
Authors: Kuniss Nadine , Kramer Guido , Müller Ulrich A. , Wolf Gunter , Kloos Christof 
Published: April 2021

Abstract
Objective
The aim of the present study was to assess diabetes-related distress in inpatients and its association with metabolic control in people with diabetes type 1 (DM1) and type 2 (DM2).

Research design and methods
In a cross-sectional study, 107 inpatients with DM1 (age 45.9 years, diabetes duration 18.7 years, HbA1c 8.4%/67.8 mmol/mol) and 109 with DM2 (age 62.0 years, diabetes duration 16.2 years, HbA1c 8.9%/74.3 mmol/mol) from a University department for endocrinology and metabolic diseases (Germany) were included over 2 years. Diabetes-related distress was assessed with the PAID questionnaire (range 0–100, higher scores imply higher diabetes-related distress, cut-off ≥ 40). The PAID questionnaire was completed by 214 of 216 participants.

Results
Fifty-one of 214 individuals (23.8%) showed high distress (PAID score ≥ 40). The mean PAID score was 28.1 ± 17.5 in all participants with no difference between DM1 and DM2 (28.1 ± 17.4 vs. 26.2 ± 16.9, p = 0.532). Individuals with DM2 on insulin scored higher than patients without insulin (27.8 ± 17.6 vs. 18.7 ± 8.5, p = 0.004). Additionally, people with DM1 treated with a system for continuous glucose monitoring (n = 50, 33.1 ± 18.8) scored higher than participants without such system (n = 32, 20.6 ± 13.3, p = 0.001). HbA1c was not correlated with the PAID score in both, DM1 (r = 0.040, p = 0.684) and DM2 (r = − 0.024, p = 0.804). Participants with DM2 and severe hypoglycaemia/last 12 months scored higher than people without (PAID score 43.0 ± 20.4 vs. 25.1 ± 16.5, p = 0.026). Frequency of non-severe hypoglycaemia was not associated with the PAID score in DM1 and DM2.

Conclusions
Patients with diabetes treated in hospital for problems with diabetes suffer frequently from diabetes-related distress (~ 24%) regardless of diabetes type.
Molecular mechanisms of vitamin D plus Bisphenol A effects on adipogenesis in human adipose-derived mesenchymal stem cells
Authors: Salehpour Amin , Shidfar Farzad , Hedayati Mehdi , Farshad Ali Asghar , Tehrani Asal Neshatbini , Mohammadi Saeed 
Published: April 2021

AbstractBackgroundObesity is considered a major health concern and mounting evidence suggests that the exposure to environmental endocrine disruptors, including Bisphenol-A (BPA), may enhance the risk to develop the disease. Moreover, growing documents propose that the vitamin D may contribute to adipogenic signaling and lipid accumulation during adipocyte differentiation. We focused on the molecular mechanism of vitamin D and BPA in human adipose-derived mesenchymal stem cells (hADMSCs) which vitamin D and BPA may influence adipose tissue development and function.MethodsHuman adipose-derived mesenchymal stem cells were cultured for 14 days in lipogenic differentiation media containing continuous concentrations of vitamin D plus BPA (0.1 nM or 10 nM). The expression of adipogenic markers including the peroxisome proliferator-activated receptor γ (PPARγ), CCAAT-enhancer-binding protein α (C/EBP α) CCAAT-enhancer-binding protein β (C/EBP β), fatty acid synthase (FASN), lipoprotein lipase (LPL), sterol regulatory element-binding protein-1c (SREBP1c), insulin-induced gene-2 (INSIG2), vitamin D receptor (VDR), estrogen receptor-beta (ER-β), fatty acid-binding protein-4 (FABP4), and glucose transporter-4 (GLUT4) was measured using Quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). Lipid accumulation was visualized with staining with Oil Red O.ResultsIn the morphological assessment of mesenchymal stem cells treated with a concentration of 10 nM vitamin D plus BPA, more lipid accumulations were observed in comparison with the group with 0.1 nM concentration. Treatment of hADMSCs with vitamin D plus BPA (0.1 nM) significantly inhibited the induction of PPARγ, C/EBP β, C/EBP α, and FASN related to adipocyte differentiation and development. However, the exposure of cells to the concentration of 10 nM vitamin D plus BPA induced the expression of these genes associated to the adipogenesis. The remarkable increase in the level of SREBP1c was associated to the suppression of INSIG2 in treated preadipocytes with 10 nM vitamin D plus BPA. Our findings showed that the expression of VDR, ERβ, GLUT4, and FABP4 were upregulated through differentiation with the highest concentrations in 0.1 nM vitamin D plus BPA group for VDR, ERβ, and GLUT4.ConclusionsVitamin D plus BPA at concentration of 10 nM boosted the adipogenesis during the critical stages of adipocytes development, whereas it seems to inhibit this process at concentration of 0.1 nM.
Correlations between isokinetic knee torques and single-leg hop distances in three directions in patients after ACL reconstruction
Authors: Aizawa Junya , Hirohata Kenji , Ohji Shunsuke , Ohmi Takehiro , Mitomo Sho , Koga Hideyuki , Yagishita Kazuyoshi 
Published: April 2021

AbstractBackgroundWhen planning rehabilitation and conditioning for performance enhancement and a return to sports after anterior cruciate ligament reconstruction, identifying the elements of physical function associated with single-leg hop is important. The purpose of this study was to clarify the relationship between single-leg hop distances in three directions and knee extensor and flexor strengths at 6 months after reconstruction.MethodsParticipants were 47 patients taking part in training sessions for sports involving cutting, pivoting, and jump-landing 6 months after reconstruction using a hamstring tendon. Single-leg hop distances in 3 directions (anterior, lateral, and medial) and isokinetic concentric strengths of knee extension and flexion were assessed at an angular velocity of 60°/s and 180°/s. Simple regression analyses using Spearman’s rank correlation coefficient were performed to assess relationships between single-leg hop distances and knee strengths.ResultsIn the involved limb, correlations between single-leg hop distances in 3 directions and knee strengths were significant (P< 0.01) and correlation coefficients ranged from 0.48 to 0.65. Correlation coefficients between all single-leg hop parameters and knee extension/flexion strengths at an angular velocity of 180°/s were greater than those of 60°/s.ConclusionsIn this cross-sectional study of patients who participated in sports training sessions that required jump-landings and cutting approximately 6 months after reconstruction using hamstring grafts, isokinetic knee flexor, and extensor torques were moderately to strongly associated with single-leg hop distances in lateral, medial, and anterior directions. Given these relationships, assessments and exercises for knee strength and single-leg hop distances should be planned.
Associations among phthalate exposure, DNA methylation of TSLP, and childhood allergy
Authors: Wang Wan-Ru , Chen Nai-Tzu , Hsu Nai-Yun , Kuo I-Ying , Chang Hsin-Wen , Wang Jiu-Yao , Su Huey-Jen 
Published: April 2021

Abstract
Background
Dysregulation of thymic stromal lymphopoietin (TSLP) expressions is linked to asthma and allergic disease. Exposure to phthalate esters, a widely used plasticizer, is associated with respiratory and allergic morbidity. Dibutyl phthalate (DBP) causes TSLP upregulation in the skin. In addition, phthalate exposure is associated with changes in environmentally induced DNA methylation, which might cause phenotypic heterogeneity. This study examined the DNA methylation of the TSLP gene to determine the potential mechanism between phthalate exposure and allergic diseases.

Results
Among all evaluated, only benzyl butyl phthalate (BBzP) in the settled dusts were negatively correlated with the methylation levels of TSLP and positively associated with children’s respiratory symptoms. The results revealed that every unit increase in BBzP concentration in the settled dust was associated with a 1.75% decrease in the methylation level on upstream 775 bp from the transcription start site (TSS) of TSLP (β =  − 1.75, p = 0.015) after adjustment for child’s sex, age, BMI, parents’ smoking status, allergic history, and education levels, PM2.5, formaldehyde, temperature; and relative humidity. Moreover, every percentage increase in the methylation level was associated with a 20% decrease in the risk of morning respiratory symptoms in the children (OR 0.80, 95% CI 0.65–0.99).

Conclusions
Exposure to BBzP in settled dust might increase children’s respiratory symptoms in the morning through decreasing TSLP methylation. Therefore, the exposure to BBzP should be reduced especially for the children already having allergic diseases.
The crucial roles of N6-methyladenosine (m6A) modification in the carcinogenesis and progression of colorectal cancer
Authors: Fang Zhihao , Hu Yiqiu , Hu Jinhui , Huang Yanqin , Zheng Shu , Guo Cheng 
Published: April 2021

AbstractAs the predominant modification in RNA, N6-methyladenosine (m6A) has attracted increasing attention in the past few years since it plays vital roles in many biological processes. This chemical modification is dynamic, reversible and regulated by several methyltransferases, demethylases and proteins that recognize m6A modification. M6A modification exists in messenger RNA and affects their splicing, nuclear export, stability, decay, and translation, thereby modulating gene expression. Besides, the existence of m6A in noncoding RNAs (ncRNAs) could also directly or indirectly regulated gene expression. Colorectal cancer (CRC) is a common cancer around the world and of high mortality. Increasing evidence have shown that the changes of m6A level and the dysregulation of m6A regulatory proteins have been implicated in CRC carcinogenesis and progression. However, the underlying regulation laws of m6A modification to CRC remain elusive and better understanding of these mechanisms will benefit the diagnosis and therapy. In the present review, the latest studies about the dysregulation of m6A and its regulators in CRC have been summarized. We will focus on the crucial roles of m6A modification in the carcinogenesis and development of CRC. Moreover, we will also discuss the potential applications of m6A modification in CRC diagnosis and therapeutics.
Economic evaluation of diagnostic sleep studies for obstructive sleep apnoea: a systematic review protocol
Authors: Natsky Andrea N. , Vakulin Andrew , Coetzer Ching Li Chai , McEvoy R. D. , Adams Robert J. , Kaambwa Billingsley 
Published: April 2021

Abstract
Background
Obstructive sleep apnoea (OSA) is a significant public health problem affecting a large proportion of the population and is associated with adverse health consequences and a substantial economic burden. Despite the existence of effective treatment, undiagnosed OSA remains a challenge. The gold standard diagnostic tool is polysomnography (PSG), yet the test is expensive, labour intensive and time-consuming. Home-based, limited channel sleep study testing (levels 3 and 4) can advance and widen access to diagnostic services. This systematic review aims to summarise available evidence regarding the cost-effectiveness of limited channel tests compared to laboratory and home PSG in diagnosing OSA.

Methods
Eligible studies will be identified using a comprehensive strategy across the following databases from inception onwards: MEDLINE, PsychINFO, SCOPUS, CINAHL, Cochrane Library, Emcare and Web of Science Core Collection and ProQuest databases. The search will include a full economic evaluation (i.e. cost-effectiveness, cost-utility, cost-benefit, cost-consequences and cost-minimisation analysis) that assesses limited channel tests and PSG. Two reviewers will screen, extract data for included studies and critically appraise the articles for bias and quality. Meta-analyses will be conducted if aggregation of outcomes can be performed. Qualitative synthesis using a dominance ranking matrix will be performed for heterogeneous data.

Discussion
This systematic review protocol uses a rigorous, reproducible and transparent methodology and eligibility criteria to provide the current evidence relating to the clinical and economic impact of limited channel and full PSG OSA diagnostic tests. Evidence will be examined using standardised tools specific for economic evaluation studies.

Trial registration

PROSPERO (CRD42020150130)
Profiling of somatic mutations and fusion genes in acute myeloid leukemia patients with FLT3-ITD or FLT3-TKD mutation at diagnosis reveals distinct evolutionary patterns
Authors: Guan Wei , Zhou Lei , Li Yan , Yang Erna , Liu Yangyang , Lv Na , Fu Lin , Ding Yi , Wang Nan , Fang Nan , Liu Qian , Wang Binan , Li Fuwei , Zhang Juan , Wang Maoquan , Wang Lili , Jing Yu , Li Yonghui , Yu Li 
Published: April 2021

Abstract
Background
The receptor tyrosine kinase FLT3 with internal tandem duplications within the juxtamembrane domain (FLT3-ITD) is a poor prognostic factor; however, the prognostic significance of missense mutation in the tyrosine kinase domain (FLT3-TKD) is controversial. Furthermore, the accompanying mutations and fusion genes with FLT3 mutations are unclear in acute myeloid leukemia (AML).

Methods
We investigated FLT3 mutations and their correlation with other gene mutations and gene fusions through two RNA-seq based next-generation sequencing (NGS) method and prognostic impact in 207 de novo AML patients.

Results
FLT3-ITD mutations were positive in 58 patients (28%), and FLT3-TKD mutations were positive in 20 patients (9.7%). FLT3-ITD was associated with a higher white blood cell count (WBC, mean 72.9 × 109/L vs. 24.2 × 109/L, P = 0.000), higher bone marrow blasts (mean 65.9% vs. 56.0%, P = 0.024), and NK-AML (normal karyotype) (64.8% vs. 48.4%, P = 0.043). NPM1 and DNMT3A mutations were enriched in FLT3-ITD (53.5% vs. 15.3%, P = 0.000; 34.6% vs. 13%, P = 0.003). However, the mutations of CEBPA were excluded in FLT3-AML (3.8% vs. 0% vs. 19.8%, P = 0.005). Mutations of Ras and TP53 were unlikely associated with FLT3-ITD (1.9% vs. 20.6%, P = 0.006; 0% vs. 6.1%, P = 0.04). The common fusion genes (> 10%) in FLT3-ITD had MLL-rearrangement and NUP98-rearrangement, while the common fusion genes in FLT3-TKD had AML1-ETO and MLL-rearrangement. Two novel fusion genes PRDM16-SKI and EFAN2-ZNF238 were identified in FLT3-ITD patients. Gene fusions and NPM1 mutation were mutually excluded in FLT3-ITD and FLT3-TKD patients. Their patterns of mutual exclusivity and cooperation among mutated genes suggest that additional driver genetic alterations are required and reveal two evolutionary patterns of FLT3 pathogenesis. Patients with FLT3-ITD had a lower CR (complete remission) rate, lower 3-year OS (overall survival), DFS (disease-free survival), and EFS (event-free survival) compared to FLT3wtAML. NK-AML with FLT3-ITD had a lower 3-year OS, DFS, and EFS than those without, while FLT3-TKD did not influence the survival in whole cohort and NK-AML. Besides, we found that FLT3-ITD/TET2 bimutation defined a poor prognostic subgroup.

Conclusions
Our study offers deep insights into the molecular pathogenesis and biology of AML with FLT3-ITD and FLT3-TKD by providing the profiles of concurrent molecular alterations and the clinical impact of FLT3-ITD and FLT3-TKD on AML patients.