bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of key genes in calcific aortic valve disease via weighted gene co-expression network analysis
Authors: Sun Jin-Yu , Hua Yang , Shen Hui , Qu Qiang , Kan Jun-Yan , Kong Xiang-Qing , Sun Wei , Shen Yue-Yun
Published: May 2021

Background

Calcific aortic valve disease (CAVD) is the most common subclass of valve heart disease in the elderly population and a primary cause of aortic valve stenosis. However, the underlying mechanisms remain unclear.

Methods

The gene expression profiles of GSE83453, GSE51472, and GSE12644 were analyzed by ‘limma’ and ‘weighted gene co-expression network analysis (WGCNA)’ package in R to identify differentially expressed genes (DEGs) and key modules associated with CAVD, respectively. Then, enrichment analysis was performed based on Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, DisGeNET, and TRRUST database. Protein–protein interaction network was constructed using the overlapped genes of DEGs and key modules, and we identified the top 5 hub genes by mixed character calculation.

Results

We identified the blue and yellow modules as the key modules. Enrichment analysis showed that leukocyte migration, extracellular matrix, and extracellular matrix structural constituent were significantly enriched. SPP1, TNC, SCG2, FAM20A, and CD52 were identified as hub genes, and their expression levels in calcified or normal aortic valve samples were illustrated, respectively.

Conclusions

This study suggested that SPP1, TNC, SCG2, FAM20A, and CD52 might be hub genes associated with CAVD. Further studies are required to elucidate the underlying mechanisms and provide potential therapeutic targets.
Risk factors for persistent abnormality on chest radiographs at 12-weeks post hospitalisation with PCR confirmed COVID-19
Authors: Wallis T. J. M. , Heiden E. , Horno J. , Welham B. , Burke H. , Freeman A. , Dexter L. , Fazleen A. , Kong A. , McQuitty C. , Watson M. , Poole S. , Brendish N. J. , Clark T. W. , Wilkinson T. M. A. , Jones M. G. , Marshall B. G.
Published: May 2021

Background

The long-term consequences of COVID-19 remain unclear. There is concern a proportion of patients will progress to develop pulmonary fibrosis. We aimed to assess the temporal change in CXR infiltrates in a cohort of patients following hospitalisation for COVID-19.

Methods

We conducted a single-centre prospective cohort study of patients admitted to University Hospital Southampton with confirmed SARS-CoV2 infection between 20th March and 3rd June 2020. Patients were approached for standard-of-care follow-up 12-weeks after hospitalisation. Inpatient and follow-up CXRs were scored by the assessing clinician for extent of pulmonary infiltrates; 0–4 per lung (Nil = 0, < 25% = 1, 25–50% = 2, 51–75% = 3, > 75% = 4).

Results

101 patients with paired CXRs were included. Demographics: 53% male with a median (IQR) age 53.0 (45–63) years and length of stay 9 (5–17.5) days. The median CXR follow-up interval was 82 (77–86) days with median baseline and follow-up CXR scores of 4.0 (3–5) and 0.0 (0–1) respectively. 32% of patients had persistent CXR abnormality at 12-weeks. In multivariate analysis length of stay (LOS), smoking-status and obesity were identified as independent risk factors for persistent CXR abnormality. Serum LDH was significantly higher at baseline and at follow-up in patients with CXR abnormalities compared to those with resolution. A 5-point composite risk score (1-point each; LOS ≥ 15 days, Level 2/3 admission, LDH > 750 U/L, obesity and smoking-status) strongly predicted risk of persistent radiograph abnormality (0.81).

Conclusion

Persistent CXR abnormality 12-weeks post COVID-19 was common in this cohort. LOS, obesity, increased serum LDH, and smoking-status were risk factors for radiograph abnormality. These findings require further prospective validation.
Effects of bilateral lung transplantation on cardiac autonomic modulation and cardiorespiratory coupling: a prospective study
Authors: Tobaldini E. , Rodrigues G. D. , Mantoan G. , Monti A. , Zelati G. Coti , Furlan Ludovico , Tarsia P. , Morlacchi L. C. , Rossetti V. , Righi I. , Rosso L. , Nosotti M. , Soares P. P. S. , Montano N. , Aliberti S. , Blasi F.
Published: May 2021

Background

Although cardiac autonomic modulation has been studied in several respiratory diseases, the evidence is limited on lung transplantation, particularly on its acute and chronic effects. Thus, we aimed to evaluate cardiac autonomic modulation before and after bilateral lung transplantation (BLT) through a prospective study on patients enrolled while awaiting transplant.

Methods

Twenty-two patients on the waiting list for lung transplantation (11 women, age 33 [24–51] years) were enrolled in a prospective study at Ospedale Maggiore Policlinico Hospital in Milan, Italy. To evaluate cardiac autonomic modulation, ten minutes ECG and respiration were recorded at different time points before (T0) and 15 days (T1) and 6 months (T2) after bilateral lung transplantation. As to the analysis of cardiac autonomic modulation, heart rate variability (HRV) was assessed using spectral and symbolic analysis. Entropy-derived measures were used to evaluate complexity of cardiac autonomic modulation. Comparisons of autonomic indices at different time points were performed.

Results

BLT reduced HRV total power, HRV complexity and vagal modulation, while it increased sympathetic modulation in the acute phase (T1) compared to baseline (T0). The HRV alterations remained stable after 6 months (T2).

Conclusion

BLT reduced global variability and complexity of cardiac autonomic modulation in acute phases, and these alterations remain stable after 6 months from surgery. After BLT, a sympathetic predominance and a vagal withdrawal could be a characteristic autonomic pattern in this population.
VWCE as a potential biomarker associated with immune infiltrates in breast cancer
Authors: Huo Qin , Li Zhenwei , Chen Siqi , Wang Juan , Li Jiaying , Xie Ni
Published: May 2021

Purpose

Von Willebrand Factor C and EGF Domains (VWCE) is an important gene that regulates cell adhesion, migration, and interaction. However, the correlation between VWCE expression and immune infiltrating in breast cancer remain unclear. In this study, we investigated the correlation between VWCE expression and immune infiltration levels in breast cancer.

Methods

The expression of VWCE was analyzed by the tumor immune estimation resource (TIMER) and DriverDB databases. Furthermore, genes co-expressed with VWCE and gene ontology (GO) enrichment analysis were investigated by the STRING and Enrichr web servers. Also, we performed the single nucleotide variation (SNV), copy number variation (CNV), and pathway activity analysis through GSCALite. Subsequently, the relationship between VWCE expression and tumor immunity was analyzed by TIMER and TISIDB databases, and further verified the results using Quantitative Real-Time PCR (RT-PCR), Western blotting, and immunohistochemistry.

Results

The results showed that the expression of VWCE mRNA in breast cancer tissue was significantly lower than that in normal tissues. We found that the expression level of VWCE was associated with subtypes, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status of breast cancer patients, but there was no significant difference in the expression of VWCE was found in age and nodal status. Further analyses indicated that VWCE was correlated with the activation or inhibition of multiple oncogenic pathways. Additionally, VWCE expression was negatively correlated with the expression of STAT1 (Th1 marker, r = − 0.12, p = 6e−05), but positively correlated with the expression of MS4A4A (r = 0.28, p = 0). These results suggested that the expression of VWCE was correlated with immune infiltration levels of Th1 and M2 macrophage in breast cancer.

Conclusions

In our study, VWCE expression was associated with a better prognosis and was immune infiltration in breast cancer. These findings demonstrate that VWCE is a potential prognostic biomarker and correlated with tumor immune cell infiltration, and maybe a promising therapeutic target in breast cancer.
Clinical applications of artificial intelligence and machine learning in cancer diagnosis: looking into the future
Authors: Iqbal Muhammad Javed , Javed Zeeshan , Sadia Haleema , Qureshi Ijaz A. , Irshad Asma , Ahmed Rais , Malik Kausar , Raza Shahid , Abbas Asif , Pezzani Raffaele , Sharifi-Rad Javad
Published: May 2021

Artificial intelligence (AI) is the use of mathematical algorithms to mimic human cognitive abilities and to address difficult healthcare challenges including complex biological abnormalities like cancer. The exponential growth of AI in the last decade is evidenced to be the potential platform for optimal decision-making by super-intelligence, where the human mind is limited to process huge data in a narrow time range. Cancer is a complex and multifaced disorder with thousands of genetic and epigenetic variations. AI-based algorithms hold great promise to pave the way to identify these genetic mutations and aberrant protein interactions at a very early stage. Modern biomedical research is also focused to bring AI technology to the clinics safely and ethically. AI-based assistance to pathologists and physicians could be the great leap forward towards prediction for disease risk, diagnosis, prognosis, and treatments. Clinical applications of AI and Machine Learning (ML) in cancer diagnosis and treatment are the future of medical guidance towards faster mapping of a new treatment for every individual. By using AI base system approach, researchers can collaborate in real-time and share knowledge digitally to potentially heal millions. In this review, we focused to present game-changing technology of the future in clinics, by connecting biology with Artificial Intelligence and explain how AI-based assistance help oncologist for precise treatment.
Methodological approaches for analysing data from therapeutic efficacy studies
Authors: Whegang Youdom Solange , Basco Leonardo K.
Published: May 2021

Several anti-malarial drugs have been evaluated in randomized clinical trials to treat acute uncomplicatedPlasmodium falciparummalaria. The outcome of anti-malarial drug efficacy studies is classified into one of four possible outcomes defined by the World Health Organization: adequate clinical and parasitological response, late parasitological failure, late clinical failure, early treatment failure. These four ordered categories are ordinal data, which are reduced to either a binary outcome (i.e., treatment success and treatment failure) to calculate the proportions of treatment failure or to time-to-event outcome for Kaplan–Meier survival analysis. The arbitrary transition from 4-level ordered categories to 2-level type categories results in a loss of statistical power. In the opinion of the authors, this outcome can be considered as ordinal at a fixed endpoint or at longitudinal endpoints. Alternative statistical methods can be applied to 4-level ordinal categories of therapeutic response to optimize data exploitation. Furthermore, network meta-analysis is useful not only for direct comparison of drugs which were evaluated together in a randomized design, but also for indirect comparison of different artemisinin-based combinations across different clinical studies using a common drug comparator, with the aim to determine the ranking order of drug efficacy. Previous works conducted in Cameroonian children served as data source to illustrate the feasibility of these novel statistical approaches. Data analysis based on ordinal end-point may be helpful to gain further insight into anti-malarial drug efficacy.
Repurposing of antibiotics for clinical management of COVID-19: a narrative review
Authors: Yacouba Abdourahamane , Olowo-okere Ahmed , Yunusa Ismaeel
Published: May 2021

Background

Drug repurposing otherwise known as drug repositioning or drug re-profiling is a time-tested approach in drug discovery through which new medical uses are being established for already known drugs. Antibiotics are among the pharmacological agents being investigated for potential anti-SARS-COV-2 activities. The antibiotics are used either to resolve bacterial infections co-existing with COVID-19 infections or exploitation of their potential antiviral activities. Herein, we aimed to review the various antibiotics that have been repositioned for the management of COVID-19.

Methods

This literature review was conducted from a methodical search on PubMed and Web of Science regarding antibiotics used in patients with COVID-19 up to July 5, 2020.

Results

Macrolide and specifically azithromycin is the most common antibiotic used in the clinical management of COVID-19. The other antibiotics used in COVID-19 includes teicoplanin, clarithromycin, doxycycline, tetracyclines, levofloxacin, moxifloxacin, ciprofloxacin, and cefuroxime. In patients with COVID-19, antibiotics are used for their immune-modulating, anti-inflammatory, and antiviral properties. The precise antiviral mechanism of most of these antibiotics has not been determined. Moreover, the use of some of these antibiotics against SARS-CoV-2 infection remains highly controversial and not widely accepted.

Conclusion

The heavy use of antibiotics during the COVID-19 pandemic would likely worsen antibiotic resistance crisis. Consequently, antibiotic stewardship should be strengthened in order to prevent the impacts of COVID-19 on the antibiotic resistance crisis.
Defining type 2 asthma and patients eligible for dupilumab in Italy: a biomarker-based analysis
Authors: Canonica Giorgio Walter , Blasi Francesco , Crimi Nunzio , Paggiaro Pierluigi , Papi Alberto , Fanelli Francesca , Stassaldi Annalisa , Furneri Gianluca
Published: May 2021

Background

Asthma is a chronic disease characterized by airway hyperresponsiveness, inflammation and mucus production. In Type 2 asthma, two phenotypic components are often co-expressed (eosinophilic and allergic). Elevated biomarker levels, such as eosinophils (EOS), fraction of exhaled nitric oxide (FeNO) and immunoglobulin E (IgE), are key clinical indicators of Type 2 inflammation. Dupilumab has been recently approved for the treatment of uncontrolled severe Type 2 asthma. Type 2 asthma includes allergic and/or eosinophilic phenotypes. The aim of this analysis was to estimate the dupilumab-eligible population in Italy and characterize it by expected biomarker status.

Methods

A 4-step approach was carried out to calculate dupilumab-eligible population. The approach consisted in: (1) estimating the total number of asthma patients in Italy (using 2016–2017 Italian-adapted Global Initiative for Asthma -GINA- guidelines); (2) estimating the number of severe asthma patients with poorly controlled or uncontrolled disease (using the findings of two recent administrative claim analyses conducted in Italy); (3) stratifying the severe uncontrolled population by biomarker levels (EOS, FeNO and IgE) according to the outcomes of the QUEST trial (a clinical study assessing the efficacy of dupilumab in patients with uncontrolled moderate-to-severe asthma; NCT02414854); (4) identifying the sub-populations of severe uncontrolled asthma patients characterised by raised blood EOS and/or FeNO level (thus indicated to receive dupilumab).

Results

According to these estimates, about 3.3 million asthmatic patients live in Italy (6.10% of the population). Of them, almost 20 thousand (N = 19,960) have uncontrolled severe asthma. Dupilumab-eligible patients would be N = 15,988, corresponding to 80.1% of the total uncontrolled severe population. Most of these patients (89.3%; N = 14,271) have at least an increase of EOS level, while slightly more than half (51.9%; N = 8,303) have raised levels of both biomarkers. Increased FeNO levels without increased EOS are observed less frequently (N = 1,717; 10.7% of the eligible population).

Conclusions

There is a strong rationale for testing all asthma biomarkers during diagnosis and disease follow-up. Given the large availability and the limited costs, these tests are cost-effective tools to detect severe Type 2 asthma, stratify patients by phenotype, and drive appropriate treatment decisions.
Exosomes derived from pioglitazone-pretreated MSCs accelerate diabetic wound healing through enhancing angiogenesis
Authors: Hu Yiqiang , Tao Ranyang , Chen Lang , Xiong Yuan , Xue Hang , Hu Liangcong , Yan Chenchen , Xie Xudong , Lin Ze , Panayi Adriana C. , Mi Bobin , Liu Guohui
Published: May 2021

Background

Enhanced angiogenesis can promote diabetic wound healing. Mesenchymal stem cells (MSCs)-derived exosomes, which are cell-free therapeutics, are promising candidates for the treatment of diabetic wound healing. The present study aimed to investigate the effect of exosomes derived from MSCs pretreated with pioglitazone (PGZ-Exos) on diabetic wound healing.

Results

We isolated PGZ-Exos from the supernatants of pioglitazone-treated BMSCs and found that PGZ-Exos significantly promote the cell viability and proliferation of Human Umbilical Vein Vascular Endothelial Cells (HUVECs) injured by high glucose (HG). PGZ-Exos enhanced the biological functions of HUVECs, including migration, tube formation, wound repair and VEGF expression in vitro. In addition, PGZ-Exos promoted the protein expression of p-AKT, p-PI3K and p-eNOS and suppressed that of PTEN. LY294002 inhibited the biological function of HUVECs through inhibition of the PI3K/AKT/eNOS pathway. In vivo modeling in diabetic rat wounds showed that pioglitazone pretreatment enhanced the therapeutic efficacy of MSCs-derived exosomes and accelerated diabetic wound healing via enhanced angiogenesis. In addition, PGZ-Exos promoted collagen deposition, ECM remodeling and VEGF and CD31 expression, indicating adequate angiogenesis in diabetic wound healing.

Conclusions

PGZ-Exos accelerated diabetic wound healing by promoting the angiogenic function of HUVECs through activation of the PI3K/AKT/eNOS pathway. This offers a promising novel cell-free therapy for treating diabetic wound healing.

Graphic abstract
Cost-effectiveness of cardiac resynchronization therapy plus an implantable cardioverter-defibrillator in patients with heart failure: a systematic review
Authors: Teimourizad Abedin , Rezapour Aziz , Sadeghian Saeed , Tajdini Masih
Published: May 2021

Introduction

Heart failure (HF) is an unusual heart function that causes reduction in cardiac or pulmonary output. Cardiac resynchronization therapy (CRT) is a mechanical device that helps to recover ventricular dysfunction by pacing the ventricles. This study planned to systematically review cost-effectiveness of CRT combined with an implantable cardioverter-defibrillator (ICD) versus ICD in patients with HF.

Methods

We used five databases (NHS Economic Evaluation Database, Cochrane Library, Medline, PubMed, and Scopus) to systematically reviewed studies published in the English language on the cost-effectiveness of CRT with defibrillator (CRT-D) Vs. ICD in patients with HF over 2000 to 2020. Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist was applied to assess the quality of the selected studies.

Results

Five studies reporting the cost-effectiveness of CRT-D vs ICD were finally identified. The results revealed that time horizon, direct medical costs, type of model, discount rate, and sensitivity analysis obviously mentioned in almost all studies. All studies used quality-adjusted life years (QALYs) as an effectiveness measurement. The highest and the lowest Incremental cost-effectiveness ratio (ICER) were reported in the USA ($138,649per QALY) and the UK ($41,787per QALY), respectively.

Conclusion

Result of the study showed that CRT-D compared to ICD alone was the most cost-effective treatment in patients with HF.
The impact of vitamin D supplementation on body fat mass in elite male collegiate athletes
Authors: Kawashima Itaru , Tsukahara Takashi , Kawai Ryosuke , Mizuno Takafumi , Ishizuka Shinya , Hiraiwa Hideki , Imagama Shiro
Published: May 2021

Background

Whether vitamin D supplementation has any effect on body fat percentage, especially among elite athletes, remains unclear. The aim of this study was to evaluate the effect of vitamin D supplementation on serum vitamin D level in elite male collegiate athletes and to analyze its effect on body fat percentage.

Methods

We enrolled a total of 42 elite male collegiate athletes in this prospective cohort study. In March 2020, body composition monitoring and blood test were performed. All athletes were provided with vitamin D3 supplement tablets of 25 μg/day. The use of the supplement was dependent on athletes’ preference. During the study period, their club activities were stopped for 2 months due to the coronavirus disease 2019 outbreak. A second examination, similar to the first one, was performed after approximately 3 months. Supplement usage by each athlete was also confirmed. The participants were divided into a non-supplement group (without supplementation, n = 15) and a supplement group (with supplementation, n = 27).

Results

Regarding baseline data at initial examination, the non-supplement and supplement groups showed significant differences in the mean body fat percentage (9.0% and 12.1%, respectively; P = 0.03) and serum 25(OH)D level (22.7 and 18.5 ng/mL, respectively, P = 0.02). At the time of the second examination, there were no significant differences in the results of both the groups. In terms of mean change value from the first to the second examination, there were significant differences in body fat percentage (1.9 and 0.2%, respectively, P = 0.02) and serum 25(OH)D level (1.7 and 7.2 ng/mL, respectively, P < 0.001) between the two groups.

A significant negative correlation was observed between the change ratio of body fat percentage and change value of serum 25(OH)D level (r =  − 0.37, P = 0.02).

Conclusions

Vitamin D supplementation of 25 μg/day significantly increased the serum 25(OH)D level in elite male collegiate athletes. Vitamin D supplementation may play a role in maintaining athletes’ body fat percentage under circumstances where sports activity has decreased.
Neohesperidin promotes the osteogenic differentiation of bone mesenchymal stem cells by activating the Wnt/β-catenin signaling pathway
Authors: Chang Yue-wen , Zhu Wen-jun , Gu Wei , Sun Jun , Li Zhi-qiang , Wei Xiao-en
Published: May 2021

Background

Osteoporosis is a common disease in aging populations. However, osteoporosis treatment is still challenging. Here, we aimed to investigate the role of neohesperidin (NEO) in osteoporosis progression and the potential mechanism.

Methods

Bone mesenchymal stem cells (BMSCs) were isolated and treated with different concentrations of NEO (0, 10, 30, 100 μM). Cell proliferation was analyzed by cell count kit-8 (CCK-8) assay. RNA-sequencing was performed on the isolated BMSCs with control and NEO treatment. Differentially expressed genes were obtained by R software. Alkaline phosphatase (ALP) staining and Alizarin red staining (ARS) were performed to assess the osteogenic capacity of the NEO. qRT-PCR was used to detect the expression of osteoblast markers.

Western blot was used to evaluate the protein levels in BMSCs.

Results

NEO treatment significantly improved hBMSC proliferation at different time points, particularly when cells were incubated with 30 μM NEO (P < 0.05). NEO dose-dependently increased the ALP activity and calcium deposition than the control group (P < 0.05). A total of 855 differentially expressed genes were identified according to the significance criteria of log2 (fold change) > 1 and adj P < 0.05. DKK1 partially reversed the promotion effects of NEO on osteogenic differentiation of BMSCs. NEO increased levels of the β-catenin protein in BMSCs.

Conclusion

NEO plays a positive role in promoting osteogenic differentiation of BMSCs, which was related with activation of Wnt/β-catenin pathway.
Corticosteroids or platelet-rich plasma injections for rotator cuff tendinopathy: a randomized clinical trial study
Authors: Dadgostar Haleh , Fahimipour Farinaz , Pahlevan Sabagh Alireza , Arasteh Peyman , Razi Mohammad
Published: May 2021

Background

Studies evaluating the role of both corticosteroids and platelet-rich plasma (PRP) in the treatment of rotator cuff (RC) tendinopathies have been contradicting.

We compared structural and clinical changes in RC muscles after corticosteroids and PRP injections.

Methods

This is a randomized double-blind clinical trial. All individuals with diagnosis of RC tendinitis during 2014–2017 were considered. Individuals were randomly allocated to either receive PRP or corticosteroids.

Overall, 3cc of PRP was injected within the subacromial joint and another 3cc was injected at the site of the tendon tear, under the guide of sonography. For the corticosteroid group, 1cc of Depo-medrol 40mg and 1cc of lidocaine (2%) was injected within the subacromial joint.

Results

Overall, 58 patients entered the study. Comparison of pain, range of motion (ROM), Western Ontario RC (WORC), Disability of Arm-Hand-Shoulder (DASH) scores, and supraspinatus thickness showed significant improvement during follow-ups in both groups (p<0.05).

During 3 months of follow-up, pain improvement was significantly better within the PRP group during (from 6.66±2.26 to 3.08±2.14 and 5.53±1.80 to 3.88±1.99, respectively; p=0.023). Regarding ROM, the PRP group had significant improvement in adduction (20.50°±8.23° to 28°±3.61° and 23.21°±7.09° to 28.46°±4.18° for the PRP and corticosteroid groups, respectively; p=0.011) and external rotation (59.66°±23.81° to 76.66°±18.30° and 57.14°±24.69° to 65.57°±26.39°, for the PRP and corticosteroid groups, respectively; p=0.036) compared to the corticosteroid group.

Conclusion

We found that PRP renders similar results to that of corticosteroids in most clinical aspects among patients with RC tendinopathies; however, pain and ROM may show more significant improvement with the use of PRP. Considering that the use of corticosteroids may be contraindicated in some patients and may be associated with the risk of tendon rupture, we suggest the use of PRP in place of corticosteroid-based injections among patients with RC tendinopathy.

Trial registration

Clinical trial registration code: IRCT201302174251N9
Gut microbiota changes after metabolic surgery in adult diabetic patients with mild obesity: a randomised controlled trial
Authors: Lau Eva , Belda Eugeni , Picq Paul , Carvalho Davide , Ferreira-Magalhães Manuel , Silva Maria Manuel , Barroso Isaac , Correia Flora , Vaz Cidália Pina , Miranda Isabel , Barbosa Adelino , Clément Karine , Doré Joel , Freitas Paula , Prifti Edi
Published: May 2021

Background

Roux-en-Y gastric bypass (RYGB) surgery is one of the most efficient procedures for the treatment of obesity, also improving metabolic and inflammatory status, in patients with mild obesity. The underlying mechanisms have not been fully understood, but gut microbiota is hypothesized to play a key role. Our aim was to evaluate the association between gut microbiota changes and anthropometric, metabolic and inflammatory profiles after metabolic surgery compared with medical therapy, in type 2 diabetic (T2DM) adults with mild obesity (BMI 30–35 kg/m2).

Methods

DM2 was an open-label, randomised controlled clinical trial (RCT: ISRCTN53984585) with 2 arms: (i) surgical, and (ii) medical. The main outcome was gut microbiota changes after: metabolic surgery (Roux-en-Y gastric bypass—RYGB) versus standard medical therapy. Secondary outcomes included anthropometric, metabolic and inflammatory profiles. Clinical visits, blood workup, and stool samples were collected at baseline and months (M)1, 3, 6, 12. Gut microbiota was profiled using 16S rRNA targeted sequencing.

Results

Twenty patients were included: 10 in surgical and 10 in medical arm. Anthropometric and metabolic comparative analysis favoured RYGB over medical arm. At M12, the percentage of weight loss was 25.5 vs. 4.9% (p < 0.001) and HbA1c was 6.2 vs. 7.7% (p < 0.001) respectively. We observed a continuous increase of genus richness after RYGB up until M12. In the medical arm, genus richness ended-up being significantly lower at M12. Composition analysis indicated significant changes of the overall microbial ecosystem (permanova p = 0.004, [R2 = 0.17]) during the follow-up period after RYGB. There was a strong association between improvement of anthropometric/metabolic/inflammatory biomarkers and increase in microbial richness and Proteobacterial lineages.

Conclusions

This was the first RCT studying composite clinical, analytic, and microbiome changes in T2DM patients with class 1 obesity after RYGB versus standard medical therapy. The remarkable phenotypic improvement after surgery occurred concomitantly with changes in the gut microbiome, but at a lower level.

Trial registration: ISRCTN53984585
Genome data of four Pythium insidiosum strains from the phylogenetically-distinct clades I, II, and III
Authors: Krajaejun Theerapong , Kittichotirat Weerayuth , Patumcharoenpol Preecha , Rujirawat Thidarat , Lohnoo Tassanee , Yingyong Wanta
Published: May 2021

Objectives

We employed the Illumina NGS platform to sequence genomes of 4 different strains of the pathogenic oomycete Pythium insidiosum, the causative agent of pythiosis. These strains were isolated from humans in Thailand (n = 3) and the United States (n = 1), and phylogenetically classified into clade-I, -II, and -III. Our study augmented the completeness of the P. insidiosum genome database for exploration of the biology, evolution, and pathogenesis of the pathogen.

Data description

One paired-end library (180-bp insert) was prepared from a gDNA sample of P. insidiosum strains ATCC200269 (clade-I), Pi19 (clade-II), MCC18 (clade-II), and SIMI4763 (clade-III) for whole-genome sequencing by Illumina HiSeq2000/HiSeq2500 NGS platform. A range of 28.4–59.4 million raw reads, accounted for 3.0–7.3 Gb, were obtained and assembled into the genome sizes of 47.1 Mb (15,153 contigs; 85% completeness; 19,329 open reading frames [ORFs]) for strain ATCC200269, 35.4 Mb (14,576 contigs; 83% completeness; 13,895 ORFs) for strain Pi19, 34.5 Mb (11,084 contigs; 84% completeness; 13,249 ORFs) for strain MCC18, and 47.1 Mb (15,162 contigs; 85% completeness; 19,340 ORFs) for strain SIMI4763. The genome data can be downloaded from the NCBI/DDBJ databases under the accessions BCFN00000000.1 (ATCC200269), BCFS00000000.1 (Pi19), BCFT00000000.1 (MCC18), and BCFU00000000.1 (SIMI4763).
High-dose vitamin-C induced prolonged factitious hyperglycemia in a peritoneal dialysis patient: a case report
Authors: Lachance Olivier , Goyer François , Adhikari Neill K. J. , Masse Marie-Hélène , Bilodeau Jean-François , Lamontagne François , Leclair Marc-André
Published: May 2021

Background

High-dose vitamin C is increasingly used for sepsis and more recently for coronavirus disease 2019 (COVID-19) infections. Proponents argue that the low cost and near perfect safety profile of vitamin C support its early adoption. Yet, adverse events might be underreported and underappreciated.

Case presentation

We report a 73-year-old non-diabetic white man with end-stage renal disease on peritoneal dialysis admitted to the intensive care unit with septic shock that was suspected to be due to peritonitis. The patient was enrolled in LOVIT (Lessening Organ Dysfunction with VITamin C; ClinicalTrials.gov identifier: NCT03680274), a randomized placebo-controlled trial of high-dose intravenous vitamin C. He developed factitious hyperglycemia, as measured with a point-of-care glucometer, that persisted for 6 days after discontinuation of the study drug, confirmed to be vitamin C after unblinding. He also had short-lived iatrogenic coma because of hypoglycemia secondary to insulin administration. These events triggered a protocol amendment.

Conclusions

Although factitious hyperglycemia has been reported before using certain glucometers in patients treated with high-dose vitamin C, the persistence of this phenomenon for 6 days after the discontinuation of the therapy is a distinguishing feature. This case highlights the importance of monitoring glucose with a core laboratory assay for up to a week in specific populations, such as patients on peritoneal dialysis.
The Rotary Cell Culture System increases NTRK3 expression and promotes neuronal differentiation and migratory ability of neural stem cells cultured on collagen sponge
Authors: Cui Yi , Yin Yanyun , Zou Yunlong , Zhao Yannan , Han Jin , Xu Bai , Chen Bing , Xiao Zhifeng , Song Hongwei , Shi Ya , Xue Weiwei , Ma Xu , Dai Jianwu
Published: May 2021

Background

Recently, neural stem cell (NSC) therapy has shown promise for the treatment of many neurological diseases. Enhancing the quality of implanted cells and improving therapeutic efficacy are currently research hotspots. It has been reported that collagen sponge material provided sufficient room for cell growth in all directions and promoted the absorption of nutrients and removal of wastes. And also, the Rotary Cell Culture System (RCCS), which mimics the microgravity environment, can be used to culture cells for tissue engineering.

Materials and methods

We performed the mRNA and miRNA sequencing to elucidate the regulatory mechanism of NSCs cultured on the collagen sponge in the RCCS system. The luciferase assay and Western blot revealed a direct regulatory role between let-7i-5p and neurotrophic receptor tyrosine kinase 3 (NTRK3; also called TrkC). And then, the neural differentiation markers Tuj1 and Map2 were detected by immunofluorescence staining. In the meantime, the migratory ability of NSCs was detected both in vitro and in spinal cord injury animals.

Results

In this study, we demonstrated that the expression of NTRK3 was elevated in NSCs cultured on collagen sponge in the RCCS system. Furthermore, increased NTRK3 expression was regulated by the downregulation of let-7i-5p. Compared to traditionally cultured NSCs, the NSCs cultured on collagen sponge in the RCCS system exhibited better neuronal differentiation and migratory ability, especially in the presence of NT-3.

Conclusions

As the biological properties and quality of transplanted cells are critical for therapeutic success, the RCCS system combined with the collagen sponge culture system shows promise for applications in clinical practice in the future.
Authentication strategies in vehicular communications: a taxonomy and framework
Authors: Rezazadeh Baee Mir Ali , Simpson Leonie , Boyen Xavier , Foo Ernest , Pieprzyk Josef
Published: May 2021

In intelligent vehicular networks, vehicles have enhanced sensing capabilities and carry computing and communication platforms to enable new versatile systems known as Vehicular Communication (VC) systems. Vehicles communicate with other vehicles and with nearby fixed equipment to support different applications, including those which increase driver awareness of the surroundings. This should result in improved safety and may optimize traffic. However, VC systems are vulnerable to cyber attacks involving message manipulation. Research aimed at tackling this problem has resulted in the proposal of multiple authentication protocols. Several existing survey papers have attempted to classify some of these protocols based on a limited set of characteristics. However, to date there is no generic framework to support the comparison of these protocols and provide guidance for design and evaluation. Most existing classifications either use computation complexity of cryptographic techniques as a criterion, or they fail to make connections between different important aspects of authentication. This paper provides such a framework, proposing a new taxonomy to enable a consistent means of classifying authentication schemes based upon seven main criteria. The main contribution of this study is a framework to enable protocol designers and investigators to adequately compare and select authentication schemes when deciding on particular protocols to implement in an application. Our framework can be applied in design, making choices appropriate for the intended context in both intra-vehicle and inter-vehicle communications. We demonstrate the application of our framework using two different types of case study: individual analysis and hypothetical design. Additionally, this work makes several related contributions. We present the network model, outline the applications, list the communication patterns and the underlying standards, and discuss the necessity of using cryptography and key management in VC systems. We also review the threats, authentication, and privacy requirements in vehicular networks.
Vaginal progesterone for prevention of preterm birth in asymptomatic high-risk women with a normal cervical length: a systematic review and meta-analysis protocol
Authors: Williams Kimberley P. , McAuliffe Liam , Diacci Rosanna , Aubin Anne-Marie , Issah Ashad , Wang Carol , Phung Jason , Pennell Craig E.
Published: May 2021

Background

Preterm birth (PTB) is estimated to affect 14.9 million babies globally every year. Global rates of PTB continue to increase from 9.8 to 10.6% over a 15-year period from 2000 to 2014. Vaginal progesterone is commonly used by clinicians as a prevention strategy, with recent evidence affirming the benefit of vaginal (micronised) progesterone to prevent PTB in women with a shortened cervix (< 25 mm). Given the low incidence of a short cervix at mid-gestation in high-risk populations further evidence is required. The objective of this review is to determine if vaginal progesterone reduces spontaneous preterm birth (sPTB) before 37 weeks in asymptomatic high-risk women with a singleton pregnancy with a normal mid-gestation cervical length.

Methods

Studies will be sourced from MEDLINE, Embase and Cochrane Register of Trials (CENTRAL) from their inception onwards with the search terms ‘progesterone’ and ‘preterm birth’. Studies will be screened and included if they assess vaginal progesterone compared to placebo in women with a normal cervical length. The primary outcome will be sPTB < 37 weeks, with secondary outcomes of sPTB < 34 weeks.

Two independent reviewers will conduct study screening at abstract and full text level, data extraction and risk of bias assessment with disagreements resolved by an experienced researcher. The Mantel-Haenszel statistical method and random effects analysis model will be used to produce treatment effect odds ratios and corresponding 95% confidence intervals.

Discussion

This review will assess the current body of evidence and provide clarity regarding the potential benefits and best practice of use of vaginal progesterone in asymptomatic women with high-risk singleton pregnancies and normal cervical length.

Trial registration

PROSPEROCRD42020152051
Correction to: Vitality models found useful in modeling tag-failure times in acoustic-tag survival studies
Authors: Skalski John R. , Whitlock Steven L.
Published: May 2021

An amendment to this paper has been published and can be accessed via the original article.
Hybridisation in kiwi (Apteryx; Apterygidae) requires taxonomic revision for the Great Spotted Kiwi
Authors: Shepherd Lara D. , Tennyson Alan J. D. , Robertson Hugh A. , Colbourne Rogan M. , Ramstad Kristina M.
Published: May 2021

Background

Kiwi (Apteryx spp.) are flightless ratites from New Zealand whose numbers and distributions have declined following human arrival. Some of the kiwi species are known to hybridise but the extent of hybridization is unknown.

Methods

We reviewed hybridisation in kiwi (Apteryx spp.) and present new genetic data examining the extent of hybridisation between Rowi (A. rowi) and Little Spotted Kiwi (A. owenii) at Okarito, the location of the only remaining natural population of the threatened Rowi. We also genetically examined the syntype specimens of A. haastii Potts, 1872, collected from near Okarito in the 1870s, which have unusual morphologies.

Results

We found evidence of recurrent hybridisation between Rowi and Little Spotted Kiwi over the last 150 years, including one F1 hybrid found in the last 15 years, despite Little Spotted Kiwi’s likely extinction on the mainland in the 1970s. However, we found little evidence of introgression of Little Spotted Kiwi alleles into the extant Rowi population. The syntype specimens of A. haastii were also found to be hybrids between Little Spotted Kiwi and Rowi.

Conclusions

Our genetic analyses indicate that, although we detected multiple instances of hybridisation between Rowi and Little Spotted Kiwi, it does not appear to be an ongoing threat to Rowi. Because the syntype specimens of A. haastii are hybrids and therefore not representative of the prevailing usage of the name for the Great Spotted Kiwi (A. haastii), we resurrect the nomen oblitum A. maxima Sclater and Hochstetter, 1861 for the large spotted kiwi species.
High School Basketball Coach and Player Perspectives on Warm-Up Routines and Lower Extremity Injuries
Authors: Munoz-Plaza Corrine , Pounds Dana , Davis Anna , Park Stacy , Sallis Robert , Romero Manuel G. , Sharp Adam L.
Published: May 2021

Background

While participation in sports-related activities results in improved health outcomes, high school athletes are at risk for lower extremity injuries, especially ankle, knee, and thigh injuries. Efforts to promote the adoption and implementation of evidence-driven approaches to reduce injury risk among school-aged athletes are needed. However, there is limited research regarding the perceived barriers, facilitators, and adherence factors that may influence the successful implementation of effective warm-up routines among this population.

Methods

We conducted a qualitative study using semi-structured interviews and focus groups to assess high school basketball coach and player current practices, knowledge, and perspectives about warm-ups and lower-extremity injuries (LEIs). We interviewed coaches (n = 12) and players (n = 30) from May to October 2019. Participants were recruited from public high schools in a joint school district in Southern California. Multiple coders employed thematic analysis of the data using validated methods.

Results

Coaches and players reported regular engagement (e.g., daily) in warm-up routines, but the time dedicated (range 5–45 min), types of exercises, and order varied substantially. Players often co-lead the warm-up practice with the coach or assistant coach. Despite regular engagement in warm-up, players and coaches report multiple challenges, including (1) limited time and space to warm-up effectively at games, (2) a perception that young players are not prone to injury, (3) competing demands for coaches’ time during practice, and (4) coaches’ lack of knowledge. Coaches and players perceive that warming up before practice will result in fewer injuries, and many players are motivated to warm up as a result of their personal injury experience; however, they desire guidance on the ideal exercises for preventing injury and training on the proper form for each exercise.

Conclusions

Regular involvement in basketball warm-up routines is common among high school teams, but the methods and time dedicated to these practices varied. Players and coaches are eager for more information on warm-up programs shown to reduce LEIs.
Community-based geographical distribution of Mycobacterium ulcerans VNTR-genotypes from the environment and humans in the Nyong valley, Cameroon
Authors: Zeukeng Francis , Ablordey Anthony , Kakou-Ngazoa Solange E. , Ghogomu Stephen Mbigha , N’golo Coulibaly David , Nsoga Marie Thérèse Ngo , Mbacham Wilfred Fon , Bigoga Jude Daiga , Djouaka Rousseau
Published: May 2021

Background

Genotyping is a powerful tool for investigating outbreaks of infectious diseases and it can provide useful information such as identifying the source and route of transmission, and circulating strains involved in the outbreak. Genotyping techniques based on variable number of tandem repeats (VNTR) are instrumental in detecting heterogeneity in Mycobacterium ulcerans (MU) and also for discriminating MU from other mycobacteria species. Here, we describe and map the distribution of MU genotypes in Buruli ulcer (BU) endemic communities of the Nyong valley in Cameroon. We also tested the hypothesis of whether the suspected animal reservoirs of BU that share the human microhabitat are shedding contaminated fecal matters and saliva into their surrounding environments.

Methods

Environmental samples from suspected MU-risk factors and lesion swabs from human patients were sampled in BU-endemic communities and tested for the presence of MU by qPCR targeting three independent sequences (IS2404, IS2606, KR-B). Positive samples to MU were further genotyped by VNTR with confirmation by sequencing of four loci (MIRU1, Locus 6, ST1, Locus 19).

Results

MU was detected in environmental samples including water bodies (23%), biofilms (14%), detritus (10%), and in human patients (73%). MU genotypes D, W, and C were found both in environmental and human samples. The micro geo-distribution of MU genotypes from communities showed that genotype D is found both in environmental and human samples, while genotypes W and C are specific to environmental samples and human lesions, respectively. No obvious focal grouping of MU genotypes was observed at the community scale. An additional survey in the human microhabitat suggests that domestic and wild animals do not shed MU in their saliva and feces in sampled communities.

Conclusions

VNTR typing uncovered different MU genotypes circulating in the endemic communities of the Akonolinga district. A MU environmental genotype was found in patients, yet the mechanism of contamination remains to be investigated; and recovering MU in culture from the environment remains key priority to enable a better understanding of the mode of transmission of BU. We also conclude that excretions from suspected animals are unlikely to be major sources of MU in the Nyong Valley in Cameroon.
Blood pattern analysis—a review and new findings
Authors: Singh Prashant , Gupta Nandini , Rathi Ravi
Published: May 2021

Background

Blood is one of the most common pieces of evidence encountered at the crime scene. Due to the viscous nature of blood, unique bloodstain patterns are formed which when studied can reveal what might have happened at the scene of the crime. Blood pattern analysis (BPA), i.e., the study of shape, size, and nature of bloodstain. The focus of this paper is to understand blood and BPA. An experimental finding to understand blood stain formation using Awlata dye was conducted within the university premises under laboratory conditions. Awlata (Alta), an Indian dye used for grooming of women, was used to create fake blood stains to understand the formation of bloodstains with respect to varying heights, and their relation with spines and satellite stains was determined.

Results

When the height of dropping fake blood increased, the distance of satellite stains emerging from the fake blood stains was also increasing. From the experimental finding, it was found that satellite stains were directly proportional to height of blood stain and spines were inversely proportional.

Conclusion

It can be concluded that blood is a vital source of information and when interpreted correctly it can be used as a source of information that can aid in investigations. Thus, a relation between formation of blood stains with relation to height was established. This finding using fake blood stains can help in carrying out future studies.