bluuebunny/crossref_metadata_2025 huggingface dataset:
The ethics of explantation
Authors: Hansson Sven Ove
Published: September 2021

Background

With the increased use of implanted medical devices follows a large number of explantations. Implants are removed for a wide range of reasons, including manufacturing defects, recovery making the device unnecessary, battery depletion, availability of new and better models, and patients asking for a removal. Explantation gives rise to a wide range of ethical issues, but the discussion of these problems is scattered over many clinical disciplines.

Methods

Information from multiple clinical disciplines was synthesized and analysed in order to provide a comprehensive approach to the ethical issues involved in the explantation of medical implants.

Results

Discussions and recommendations are offered on pre-implantation information about a possible future explantation, risk–benefit assessments of explantation, elective explantations demanded by the patient, explantation of implants inserted for a clinical trial, patient registers, quality assurance, routines for investigating explanted implants, and demands on manufacturers to prioritize increased service time in battery-driven implants and to market fewer but more thoroughly tested models of implants.

Conclusion

Special emphasis is given to the issue of control or ownership over implants, which underlies many of the ethical problems concerning explantation. It is proposed that just like transplants, implants that fulfil functions normally carried out by biological organs should be counted as supplemented body parts. This means that the patient has a strong and inalienable right to the implant, but upon explantation it loses that status.
Exploring experiences of implementing standardized cancer patient pathways within investigatory units – a qualitative study
Authors: Winterling Jeanette , Delilovic Sara , Dervish Jessica , Gunarsson Malin , Åhström Mårten , Hasson Henna
Published: September 2021

Background

In the implementation of standardized cancer patient pathways (CPPs), the investigatory units, endoscopy, radiology and pathology, are crucial to ensure an eventual cancer diagnosis. However, when evaluating the implementation of CPPs, little attention has been paid to the healthcare professionals working in these units. The aim of this study was to explore experiences of the implementation of CPPs among health professionals in investigatory units.

Methods

This descriptive qualitative study included 55 health professionals working in investigatory units. Participants were interviewed in 2017–2018, and data were analysed using thematic analysis.

Results

The health professionals reported benefits, facilitators and challenges when describing their experiences of implementing CPPs. Benefits included that CPP improved collaboration and increased focus on the patients. Facilitators in the implementation process included pre-existing well-functioning work processes and having supportive functions (e.g. coordinators). Challenges included the lack of staff and clinical equipment, as well as unjustified time-slots and incorrect referrals.

Conclusions

The findings show that most health professionals working in investigatory units’ experience benefits with the implementation of CPP, but the lack of resources was especially hard to overcome.
Construction of à la carte QconCAT protein standards for multiplexed quantification of user-specified target proteins
Authors: Johnson James , Harman Victoria M. , Franco Catarina , Emmott Edward , Rockliffe Nichola , Sun Yaqi , Liu Lu-Ning , Takemori Ayako , Takemori Nobuaki , Beynon Robert J.
Published: September 2021

Background

QconCATs are quantitative concatamers for proteomic applications that yield stoichiometric quantities of sets of stable isotope-labelled internal standards. However, changing a QconCAT design, for example, to replace poorly performing peptide standards has been a protracted process.

Results

We report a new approach to the assembly and construction of QconCATs, based on synthetic biology precepts of biobricks, making use of loop assembly to construct larger entities from individual biobricks. The basic building block (a Qbrick) is a segment of DNA that encodes two or more quantification peptides for a single protein, readily held in a repository as a library resource. These Qbricks are then assembled in a one tube ligation reaction that enforces the order of assembly, to yield short QconCATs that are useable for small quantification products. However, the DNA context of the short construct also allows a second cycle of loop assembly such that five different short QconCATs can be assembled into a longer QconCAT in a second, single tube ligation. From a library of Qbricks, a bespoke QconCAT can be assembled quickly and efficiently in a form suitable for expression and labelling in vivo or in vitro.

Conclusions

We refer to this approach as the ALACAT strategy as it permits à la carte design of quantification standards. ALACAT methodology is a major gain in flexibility of QconCAT implementation as it supports rapid editing and improvement of QconCATs and permits, for example, substitution of one peptide by another.
A missense variant rs2585405 in clock gene PER1 is associated with the increased risk of noise-induced hearing loss in a Chinese occupational population
Authors: Chen Hao , Ding Xuexue , Ding Enmin , Chen Mengyao , Wang Huimin , Yang Guangzhi , Zhu Baoli
Published: September 2021

Objective

To investigate the potential association of cochlear clock genes (CRY1, CRY2, PER1, and PER2), the DNF gene (brain-derived neurotrophic factor), and the NTF3 gene (neurotrophin3) with susceptivity to noise-induced hearing loss (NIHL) among Chinese noise-exposed workers.

Methods

A nested case–control study was performed with 2056 noise-exposed workers from a chemical fiber factory and an energy company who underwent occupational health examinations in 2019 as study subjects. Propensity score matching was conducted to screen cases and controls by matching sex, age, and the consumption of tobacco and alcohol. A total of 1269 participants were enrolled. Then, general information and noise exposure of the study subjects were obtained through a questionnaire survey and on-site noise detection. According to the results of audiological evaluations, the participants were divided into the case group (n = 432, high-frequency threshold shift > 25 dB) and the matched control group (n = 837, high-frequency threshold shift ≤ 25 dB) by propensity score matching. Genotyping for PER1 rs2253820 and rs2585405; PER2 rs56386336 and rs934945; CRY1 rs1056560 and rs3809236; CRY2 rs2292910 and rs6798; BDNF rs11030099, rs7124442 and rs6265; and NTF3 rs1805149 was conducted using the TaqMan-PCR technique.

Results

In the dominant model and the co-dominant model, the distribution of PER1 rs2585405 genotypes between the case group and the control group was significantly different (P = 0.03, P = 0.01). The NIHL risk of the subjects with the GC genotype was 1.41 times the risk of those carrying the GG genotype (95% confidence interval (CI) of odds ratio (OR): 1.01–1.96), and the NIHL risk of the subjects with the CC genotype was 0.93 times the risk of those carrying the GG genotype (95%CI of OR: 0.71–1.21). After the noise exposure period and noise exposure intensities were stratified, in the co-dominant model, the adjusted OR values for noise intensities of ≤ 85 was 1.23 (95%CI: 0.99–1.53). In the dominant model, the adjusted OR values for noise exposure periods of ≤ 16 years and noise intensities of ≤ 85 were 1.88 (95%CI: 1.03–3.42) and 1.64 (95%CI: 1.12–2.38), respectively.

Conclusion

The CC/CG genotype of rs2585405 in the PER1 gene was identified as a potential risk factor for NIHL in Chinese noise-exposed workers, and interaction between rs2585405 and high temperature was found to be associated with NIHL risk.
Effect of anti-diabetic drugs in dialysis patients with diabetes: a nationwide retrospective cohort study
Authors: Ou Shih-Hsiang , Chen Hsin-Yu , Fang Nai-Wen , Yin Chun-Hao , Chen Chien-Liang , Chen Jin-Shuen
Published: September 2021

Background

Type 2 diabetes mellitus is common in patients undergoing dialysis. However, the association between anti-diabetic drug use and survival outcomes is rarely discussed. We aimed to investigate whether continued anti-diabetic medication use affects the survival of diabetic dialysis patients and whether different hypoglycemic drug use influences prognosis.

Methods

Using a nationwide database, we enrolled patients with incident end-stage renal disease under maintenance dialysis during 2011–2015 into the pre-existing diabetes dialysis (PDD), incident diabetes after dialysis (IDD), and non-diabetic dialysis (NDD) groups. The PDD group was further subclassified into patients who continued (PDD-M) and discontinued (PDD-NM) anti-diabetic drug use after dialysis.

Results

A total of 5249 dialysis patients were examined. The PDD-NM group displayed a significantly higher mortality rate than the IDD, PDD-M, and NDD groups (log-rank test P < 0.001). The PDD-M group had a significantly lower risk of death, regardless of insulin (P < 0.001) or oral hypoglycemic agent (OHA) (P < 0.001) use. Initial insulin administration or OHA had no statistically significant effect on overall mortality in the IDD group. But OHA use had better survival trends than insulin administration for the older (P = 0.02) and male subgroups (P = 0.05).

Conclusions

For dialysis patients with diabetes, continuous administration of anti-diabetic drugs after dialysis and choice of medication may affect outcomes.
Impact of insulin therapy on the mortality of acute heart failure patients with diabetes mellitus
Authors: Jang Se Yong , Jang Jieun , Yang Dong Heon , Cho Hyun-Jai , Lim Soo , Jeon Eun-Seok , Lee Sang Eun , Kim Jae-Joong , Kang Seok-Min , Baek Sang Hong , Cho Myeong-Chan , Choi Dong-Ju , Yoo Byung-Su , Kim Kye Hun , Park Sue K. , Lee Hae-Young
Published: September 2021

Background

Patients with diabetes mellitus (DM) have a higher prevalence of heart failure (HF) than those without it. Approximately 40 % of HF patients have DM and they tend to have poorer outcomes than those without DM. This study evaluated the impact of insulin therapy on mortality among acute HF patients.

Methods

A total of 1740 patients from the Korean Acute Heart Failure registry with DM were included in this study. The risk of all-cause mortality according to insulin therapy was assessed using the Cox proportional hazard models with inverse probability of treatment weighting to balance the clinical characteristics (pretreatment covariates) between the groups.

Results

DM patients had been treated with either oral hypoglycemic agents (OHAs) alone (n = 620), insulin alone (n = 682), or insulin combined with OHAs (n = 438). The insulin alone group was associated with an increased mortality risk compared with the OHA alone group (HR = 1.41, 95 % CI 1.21–1.66]). Insulin therapy combined with OHAs also showed an increased mortality risk (HR = 1.29, 95 % CI 1.14–1.46) compared with the OHA alone group. Insulin therapy was consistently associated with increased mortality risk, regardless of the left ventricular ejection fraction (LVEF) or HF etiology. A significant increase in mortality was observed in patients with good glycemic control (HbA1c < 7.0 %) receiving insulin, whereas there was no significant association in patients with poor glycemic control (HbA1c ≥ 7.0%).

Conclusions

Insulin therapy was found to be associated with increased mortality compared to OHAs. The insulin therapy was harmful especially in patients with low HbA1c levels which may suggest the necessity of specific management strategies and blood sugar targets when using insulin in patients with HF.
External applicability of SGLT2 inhibitor cardiovascular outcome trials to patients with type 2 diabetes and cardiovascular disease
Authors: Smidt Lisanne C. A. , Visseren Frank L. J. , de Ranitz-Greven Wendela L. , Nathoe Hendrik M. , Kappelle L. Jaap , de Borst Gert J. , de Valk Harold W. , Westerink Jan ,   the UCC-SMART Study Group
Published: September 2021

Background

Recent treatment guidelines support the use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with type 2 diabetes and cardiovascular disease based on the results of cardiovascular outcome trials (CVOTs). Applicability of these trials to everyday patients with type 2 diabetes and cardiovascular disease is however unknown. The aim of this study is to assess the external applicability of SGLT2i CVOTs in daily clinical practice type 2 diabetes patients with established cardiovascular disease.

Methods

Trial in- and exclusion criteria from EMPA-REG OUTCOME, CANVAS, DECLARE-TIMI 58 and VERTIS-CV were applied to 1389 type 2 diabetes patients with cardiovascular disease in the Utrecht Cardiovascular Cohort-Secondary Manifestations of ARTerial disease (UCC-SMART). To evaluate the difference in cardiovascular risk (MACE) and all-cause mortality between trial eligible and ineligible patients, age and sex-adjusted Cox-regression analyses were performed.

Results

After applying trial in- and exclusion criteria, 48% of UCC-SMART patients with type 2 diabetes and cardiovascular disease would have been eligible for DECLARE-TIMI 58, 35% for CANVAS, 29% for EMPA-REG OUTCOME and 21% for VERTIS-CV. Without the eligibility criteria of HbA1c, eligibility was 58–88%. For all trials the observed risk for cardiovascular events and all-cause mortality was similar in eligible and ineligible patients after adjustment for age and gender.

Conclusion

A large proportion of patients with type 2 diabetes and cardiovascular disease in daily clinical practice would have been eligible for participation in the SGLT2i CVOTs. Trial eligible and ineligible patients have the same risk for MACE and all-cause mortality.
Calculated identification of mutator-derived lncRNA signatures of genomic instability to predict the clinical outcome of muscle-invasive bladder cancer
Authors: Liang Yingchun , Ye Fangdie , Cheng Zhang , Ou Yuxi , Zou Lujia , Hu Yun , Hu Jimeng , Jiang Haowen
Published: September 2021

Background

Muscle-invasive bladder cancer (MIBC) is one of the most important type of bladder cancer, with a high morbidity and mortality rate. Studies have found that long non-coding RNA (lncRNA) plays a key role in maintaining genomic instability. However, Identification of lncRNAs related to genomic instability (GIlncRNAs) and their clinical significance in cancers have not been extensively studied yet.

Methods

Here, we downloaded the lncRNA expression profiles, somatic mutation profiles and clinical related data in MIBC patients from The Cancer Genome Atlas (TCGA) database. A lncRNA computational framework was used to find differentially expressed GIlncRNAs. Multivariate Cox regression analysis was used to construct a genomic instability-related lncRNA signature (GIlncSig). Univariate and multivariate Cox analyses were used to assess the independent prognostic for the GIlncSig and other key clinical factors.

Results

We found 43 differentially expressed GIlncRNAs and constructed the GIlncSig with 6 GIlncRNAs in the training cohort. The patients were divided into two risk groups. The overall survival of patients in the high-risk group was lower than that in the low-risk group (P < 0.001), which were further verified in the testing cohort and the entire TCGA cohort. Univariate and multivariate Cox regression showed that the GIlncSig was an independent prognostic factor. In addition, the GIlncSig correlated with the genomic mutation rate of MIBC, indicating its potential as a measure of the degree of genomic instability. The GIlncSig was able to divide FGFR3 wild- and mutant-type patients into two risk groups, and effectively enhanced the prediction effect.

Conclusion

Our study introduced an important reference for further research on the role of GIlncRNAs, and provided prognostic indicators and potential biological therapy targets for MIBC.
Urban malaria in sub-Saharan Africa: dynamic of the vectorial system and the entomological inoculation rate
Authors: Doumbe-Belisse P. , Kopya E. , Ngadjeu C. S. , Sonhafouo-Chiana N. , Talipouo A. , Djamouko-Djonkam L. , Awono-Ambene H. P. , Wondji C. S. , Njiokou F. , Antonio-Nkondjio C.
Published: September 2021

Sub-Saharan Africa is registering one of the highest urban population growth across the world. It is estimated that over 75% of the population in this region will be living in urban settings by 2050. However, it is not known how this rapid urbanization will affect vector populations and disease transmission. The present study summarizes findings from studies conducted in urban settings between the 1970s and 2020 to assess the effects of urbanization on the entomological inoculation rate pattern and anopheline species distribution. Different online databases such as PubMed, ResearchGate, Google Scholar, Google were screened. A total of 90 publications were selected out of 1527. Besides, over 200 additional publications were consulted to collate information on anopheline breeding habitats and species distribution in urban settings. The study confirms high malaria transmission in rural compared to urban settings. The study also suggests that there had been an increase in malaria transmission in most cities after 2003, which could also be associated with an increase in sampling, resources and reporting. Species of theAnopheles gambiaecomplex were the predominant vectors in most urban settings. Anopheline larvae were reported to have adapted to different aquatic habitats. The study provides updated information on the distribution of the vector population and the dynamic of malaria transmission in urban settings. The study also highlights the need for implementing integrated control strategies in urban settings.
CircMYH9 drives colorectal cancer growth by regulating serine metabolism and redox homeostasis in a p53-dependent manner
Authors: Liu Xin , Liu Yunze , Liu Zhao , Lin Changwei , Meng Fanchao , Xu Lei , Zhang Xiuzhong , Zhang Chong , Zhang Penbo , Gong Shuai , Wu Nai , Ren Zeqiang , Song Jun , Zhang Yi
Published: September 2021

Background

Circular RNAs (circRNAs) play important roles in cancer progression and metabolism regulation. Serine/glycine metabolism supports the growth of cancer cells by contributing to their anabolic demands and epigenome as well as by regulating their redox state. However, the role of circRNA in the regulation of serine/glycine metabolism has not been well elucidated.

Methods

Microarray analysis was used to screen differentially expressed novel circRNAs. qRT-PCR and FISH were utilized to analyzed the expression of circMYH9. CCK8, colony formation and FACS were used to analyze proliferation of colorectal cancer (CRC) cells. Xenograft experiments were used to analyze tumor growth in vivo. RNA-sequencing, immunoblot and LC–MS were used to identify the downstream metabolic pathway of circMYH9. ChIRP, Mass Spectrometry, RIP and RNA pulldown were utilized to test the interaction between circMYH9, hnRNPA2B1 and p53 pre-mRNA. ChIP-qPCR was used to analyze the binding sites of HIF-1α. Chemically-induced CRC mice were generated to evaluate the role of circMYH9 in tumorigenesis.

Results

We identified an intron-derived circRNA, circMYH9, which was significantly upregulated in CRC tissues. A higher circMYH9 level correlated with shorter relapse-free survival and overall survival of CRC patients. CircMYH9 promoted serine/glycine metabolism, the NAD + /NADH ratio, and glutathione recycling and inhibited reactive oxygen species (ROS) in a p53-dependent manner, impacting tumour growth. Mechanistically, circMYH9 destabilized the pre-mRNA of p53 by recruiting hnRNPA2B1 in the nucleus. hnRNPA2B1 bound to N6-methyladenosine sites on the 3' untranslated region of p53 pre-mRNA and maintained its stability. Moreover, a lack of amino acids led to an elevated level of ROS, resulting in increased HIF1α, which promoted circMYH9 expression by binding to the promoter region. Furthermore, in vivo AAV9-mediated transfection of circMYH9 could drive chemically-induced carcinogenesis by suppressing p53 in mice.

Conclusions

The overexpression of circMYH9 promotes CRC proliferation though modulating serine/glycine metabolism and redox homeostasis in a p53-dependent manner, and targeting circMYH9 and its pathway may be an effective strategy for the treatment of CRC.
Hydrogel-load exosomes derived from dendritic cells improve cardiac function via Treg cells and the polarization of macrophages following myocardial infarction
Authors: Zhang Youming , Cai Zichun , Shen Yunli , Lu Qizheng , Gao Wei , Zhong Xin , Yao Kang , Yuan Jie , Liu Haibo
Published: September 2021

Backgroud

Myocardial infarction (MI) is one of the leading causes of global death. Dendritic cell-derived exosomes (DEXs) provide us with the possibility of improving cardiac function after MI but are limited by low retention times and short-lived therapeutic effects. In this study, we developed a novel drug delivery system incorporating alginate hydrogel that continuously releases DEXs and investigated the mechanisms underlying the action of DEXs in the improvement of cardiac function after MI.

Results

We incorporated DEXs with alginate hydrogel (DEXs-Gel) and investigated controlled released ability and rheology, and found that DEXs-Gel release DEXs in a sustainable mammer and prolonged the retention time of DEXs but had no detrimental effects on the migration in vivo. Then DEXs-Gel was applicated in the MI model mice, we found that DEXs-Gel siginificantly enhanced the therapeutic effects of DEXs with regards to improving cardiac function after MI. Flow cytometry and immunofluorescence staining revealed that DEXs significantly upregulated the infiltration of Treg cells and M2 macrophages into the border zoom after MI, and DEXs activated regulatory T (Treg) cells and shifted macrophages to reparative M2 macrophages, both in vitro and in vivo.

Conclusion

Our novel delivery method provides an innovative tool for enhancing the therapeutic effects of DEXs after MI. Further analysis revealed that DEXs exert effect by activating Treg cells and by modifying the polarization of macrophages.

Graphic Abstract
Single-cell analysis of a tumor-derived exosome signature correlates with prognosis and immunotherapy response
Authors: Wu Jiani , Zeng Dongqiang , Zhi Shimeng , Ye Zilan , Qiu Wenjun , Huang Na , Sun Li , Wang Chunlin , Wu Zhenzhen , Bin Jianping , Liao Yulin , Shi Min , Liao Wangjun
Published: September 2021

Background

Tumor-derived exosomes (TEXs) are involved in tumor progression and the immune modulation process and mediate intercellular communication in the tumor microenvironment. Although exosomes are considered promising liquid biomarkers for disease diagnosis, it is difficult to discriminate TEXs and to develop TEX-based predictive biomarkers.

Methods

In this study, the gene expression profiles and clinical information were collected from The Cancer Genome Atlas (TCGA) database, IMvigor210 cohorts, and six independent Gene Expression Omnibus datasets. A TEXs-associated signature named TEXscore was established to predict overall survival in multiple cancer types and in patients undergoing immune checkpoint blockade therapies.

Results

Based on exosome-associated genes, we first constructed a tumor-derived exosome signature named TEXscore using a principal component analysis algorithm. In single-cell RNA-sequencing data analysis, ascending TEXscore was associated with disease progression and poor clinical outcomes. In the TCGA Pan-Cancer cohort, TEXscore was elevated in tumor samples rather than in normal tissues, thereby serving as a reliable biomarker to distinguish cancer from non-cancer sources. Moreover, high TEXscore was associated with shorter overall survival across 12 cancer types. TEXscore showed great potential in predicting immunotherapy response in melanoma, urothelial cancer, and renal cancer. The immunosuppressive microenvironment characterized by macrophages, cancer-associated fibroblasts, and myeloid-derived suppressor cells was associated with high TEXscore in the TCGA and immunotherapy cohorts. Besides, TEXscore-associated miRNAs and gene mutations were also identified. Further experimental research will facilitate the extending of TEXscore in tumor-associated exosomes.

Conclusions

TEXscore capturing tumor-derived exosome features might be a robust biomarker for prognosis and treatment responses in independent cohorts.
Bufalin suppresses tumour microenvironment-mediated angiogenesis by inhibiting the STAT3 signalling pathway
Authors: Fang Kai , Zhan Yueping , Zhu Ruiqiu , Wang Yuqian , Wu Chengqi , Sun Min , Qiu Yanyan , Yuan Zeting , Liang Xin , Yin Peihao , Xu Ke
Published: September 2021

Background

Antiangiogenic therapy has increasingly become an important strategy for the treatment of colorectal cancer. Recent studies have shown that the tumour microenvironment (TME) promotes tumour angiogenesis. Bufalin is an active antitumour compound whose efficacy has been indicated by previous studies. However, there are very few studies on the antiangiogenic effects of bufalin.

Methods

Herein, human umbilical vein endothelial cell (HUVEC) tube formation, migration and adhesion tests were used to assess angiogenesis in vitro. Western blotting and quantitative PCR were used to detect relevant protein levels and mRNA expression levels. A subcutaneous xenograft tumour model and a hepatic metastasis model were established in mice to investigate the influence of bufalin on angiogenesis mediated by the TME in vivo.

Results

We found that angiogenesis mediated by cells in the TME was significantly inhibited in the presence of bufalin. The results demonstrated that the proangiogenic genes in HUVECs, such as VEGF, PDGFA, E-selectin and P-selectin, were downregulated by bufalin and that this downregulation was mediated by inhibition of the STAT3 pathway. Overexpression of STAT3 reversed the inhibitory effects of bufalin on angiogenesis. Furthermore, there was little reduction in angiogenesis when bufalin directly acted on the cells in the tumour microenvironment.

Conclusion

Our findings demonstrate that bufalin suppresses tumour microenvironment-mediated angiogenesis by inhibiting the STAT3 signalling pathway in vascular endothelial cells, revealing that bufalin may be used as a new antiangiogenic adjuvant therapy medicine to treat colorectal cancer.
Virologic outcomes of switching to boosted darunavir plus dolutegravir with respect to history of drug resistance
Authors: Wolf Eva , Boesecke Christoph , Balogh Annamaria , Bidner Helen , Cordes Christiane , Heiken Hans , Krznaric Ivanka , Kümmerle Tim , Stellbrink Hans-Jürgen , Schneider Jochen , Spinner Christoph D. ,   the DUALIS Study Group
Published: September 2021

Objective

The DUALIS study showed that switching to boosted darunavir (bDRV) plus dolutegravir (DTG; 2DR) was non-inferior to continuous bDRV plus 2 nucleoside/nucleotide reverse-transcriptase inhibitors (NRTIs; 3DR) in treatment-experienced virologically suppressed people living with HIV (PLWH). We analyzed virologic outcomes with respect to treatment history and HIV drug resistance.

Design

Post hoc analysis of a randomized trial.

Methods

Main inclusion criteria were an HIV RNA level < 50 copies/mL for ≥ 24 weeks and no resistance to integrase strand transfer inhibitors or bDRV. Resistance-associated mutations (RAMs) were interpreted using the Stanford HIVdb mutation list. Outcomes measures were 48-week virologic response (HIV RNA < 50 copies/mL, FDA snapshot) and HIV RNA ≥ 50 copies/mL (including discontinuation due to a lack of efficacy or reasons other than adverse events and HIV RNA ≥ 50 copies/mL, referred to as snapshot non-response).

Results

The analysis population included 263 patients (2DR: 131, 3DR: 132): 90.1% males; median age, 48 years; CD4 + T-cell nadir < 200/µl, 47.0%; ≥ 2 treatment changes, 27.4%; NRTI, non-NRTI (NNRTI), and major protease inhibitor (PI) RAMs in 9.5%, 14.4%, and 3.4%, respectively. In patients with RAMs in the 2DR and 3DR groups, virologic response rates were 87.8% and 96.0%, respectively; the corresponding rates in those without RAMs were 85.7% and 81.8%. RAMs were unrelated to virologic non-response in either group. No treatment-emergent RAMs were observed.

Conclusions

DTG + bDRV is an effective treatment option without the risk of treatment-emergent resistance for PLWH on suppressive first- or further-line treatment with or without evidence of pre-existing NRTI, NNRTI, or PI RAMs.

Trial registration: EUDRA-CT Number 2015-000360-34; registered 07 April 2015; https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-000360-34/DE.
In vitro efficacy of Artemisia extracts against SARS-CoV-2
Authors: Nie Chuanxiong , Trimpert Jakob , Moon Sooyeon , Haag Rainer , Gilmore Kerry , Kaufer Benedikt B. , Seeberger Peter H.
Published: September 2021

Background

Traditional medicines based on herbal extracts have been proposed as affordable treatments for patients suffering from coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Teas and drinks containing extracts of Artemisia annua and Artemisia afra have been widely used in Africa in efforts to prevent SARS-CoV-2 infection and fight COVID-19.

Methods

The plant extracts and Covid-Organics drink produced in Madagascar were tested for plaque reduction using both feline coronavirus and SARS-CoV-2 in vitro. Their cytotoxicities were also investigated.

Results

Several extracts as well as Covid-Organics inhibited SARS-CoV-2 and FCoV infection at concentrations that did not affect cell viability.

Conclusions

Some plant extracts show inhibitory activity against FCoV and SARS-CoV-2. However, it remains unclear whether peak plasma concentrations in humans can reach levels needed to inhibit viral infection following consumption of teas or Covid-Organics. Clinical studies are required to evaluate the utility of these drinks for COVID-19 prevention or treatment of patients.
Genomic and functional characterization of five novel Salmonella-targeting bacteriophages
Authors: Kuźmińska-Bajor Marta , Śliwka Paulina , Ugorski Maciej , Korzeniowski Paweł , Skaradzińska Aneta , Kuczkowski Maciej , Narajaczyk Magdalena , Wieliczko Alina , Kolenda Rafał
Published: September 2021

Background

The host-unrestricted, non-typhoidalSalmonella entericaserovar Enteritidis (S. Enteritidis) and the serovar Typhimurium (S. Typhimurium) are major causative agents of food-borne gastroenteritis, and the host-restrictedSalmonella entericaserovar Gallinarum (S. Gallinarum) is responsible for fowl typhoid. Increasing drug resistance inSalmonellacontributes to the reduction of effective therapeutic and/or preventive options. Bacteriophages appear to be promising antibacterial tools, able to combat infectious diseases caused by a wide range ofSalmonellastrains belonging to both host-unrestricted and host-restrictedSalmonellaserovars.

Methods

In this study, five novel lyticSalmonellaphages, named UPWr_S1-5, were isolated and characterized, including host range determination by plaque formation, morphology visualization with transmission electron microscopy, and establishment of physiological parameters. Moreover, phage genomes were sequenced, annotated and analyzed, and their genomes were compared with referenceSalmonellaphages by use of average nucleotide identity, phylogeny, dot plot, single nucleotide variation and protein function analysis.

Results

It was found that UPWr_S1-5 phages belong to the genusJerseyviruswithin theSiphoviridaefamily. All UPWr_S phages were found to efficiently infect variousSalmonellaserovars. Host range determination revealed differences in host infection profiles and exhibited ability to infectSalmonella entericaserovars such as Enteritidis, Gallinarum, Senftenberg, Stanley and Chester. The lytic life cycle of UPWr_S phages was confirmed using the mitomycin C test assay. Genomic analysis revealed that genomes of UPWr_S phages are composed of 51 core and 19 accessory genes, with 33 of all predicted genes having assigned functions. UPWr_S genome organization comparison revealed 3 kinds of genomes and mosaic structure. UPWr_S phages showed very high sequence similarity to each other, with more than 95% average nucleotide identity.

Conclusions

Five novel UPWr_S1-5 bacteriophages were isolated and characterized. They exhibit host lysis range within 5 different serovars and are efficient in lysis of both host-unrestricted and host-restrictedSalmonellaserovars. Therefore, because of their ability to infect variousSalmonellaserovars and lytic life cycle, UPWr_S1-5 phages can be considered as useful tools in biological control of salmonellosis.
Prelacteal feeding practice and its associated factors among mothers having children less than 2 years of age in East Africa: a multilevel analysis of the recent demographic and health surveys
Authors: Teshale Achamyeleh Birhanu , Worku Misganaw Gebrie , Tessema Zemenu Tadesse , Tesema Getayeneh Antehunegn
Published: September 2021

Background

Prelacteal feeding is a major public health problem that increases the risk of morbidity and mortality in children. It also result delayed breastfeeding initiation and interferes with exclusive breastfeeding. Although numerous studies have been done on prelacteal feeding in individual East African countries, most of them did not consider community-level factors that could affect the likelihood of prelacteal feeding. This study, thus, aimed to assess the pooled prevalence and associated factors of prelacteal feeding practice in East Africa.

Methods

We used pooled data from the 12 east Africa countries Demographic and Health Surveys (DHS). A total weighted sample of 33,423 women was included in the final analysis. We employed multilevel logistic regression analysis to assess factors associated with prelacteal feeding practice. Finally, the Adjusted odds ratio (AOR) with 95% Confidence (CI) interval was reported and variables with p value< 0.05, in the multivariable analysis, were declared to be significant predictors of prelacteal feeding practice.

Result

In this study, the pooled prevalence of prelacteal feeding practice was 11.85% (95%CI: 11.50, 12.20) with great variation between countries, ranging from 3.08% (95%CI: 2.35, 3.81) in Malawi to 39.21% (95%CI: 36.36, 42.06) in Comoros. Both individual and community-level factors were associated with prelacteal feeding practice. Of the individual-level factors, home delivery, multiple birth, cesarean delivery, non-exposure to media, delayed initiation of breastfeeding, and being a small-sized baby were associated with higher odds of prelacteal feeding practice. Among the community-level factors, rural residence and higher community-level of media exposure were associated with lower odds of prelacteal feeding practice.

Conclusion

In this study, the pooled prevalence of prelacteal feeding is high. Both individual and community level variables were associated with prelacteal feeding practice. Therefore, individual and community-level interventions that encourage mothers to deliver in the health facility and promoting timely initiation of breastfeeding are needed to reduce prelacteal feeding practices in east Africa. Moreover, media campaigns regarding this harmful traditional practice could be strengthened.
Magnetic levitation pump versus constrained vortex pump: a pilot study on the hemolysis effect during minimal invasive extracorporeal circulation
Authors: Condello Ignazio , Santarpino Giuseppe , Serraino Giuseppe Filiberto , Mastroroberto Pasquale , Speziale Giuseppe , Nasso Giuseppe
Published: September 2021

Background

Elevated plasma free hemoglobin is associated with multi-organ injury. In this context, minimally invasive extracorporeal technologies represent a way to reduce this complication following cardiac surgery.

Methods

We present a pilot study focused on plasma free hemoglobin levels in 40 patients undergoing isolated coronary artery bypass grafting (CABG). The same circuits for minimally invasive extracorporeal circulation (MiECC) were used in all patients. The ECMOLIFE magnetic levitation pump was used in the study group (n = 20), and the AP40 Affinity CP centrifugal blood pump was used in the control group (n = 20).

Results

In the immediate postoperative period, plasma free hemoglobin (PFH) and lactate dehydrogenase (LDH) were significantly lower in the study group than in the control group (10.6 ± 0.7 vs 19.9 ± 0.3 mg/dL,p = 0.034; and 99.16 ± 1.7 vs 139.17 ± 1.5 IU/L,p = 0.027, respectively). Moreover, patients treated with the magnetic levitation pump showed lower creatinine and indirect bilirubin (0.92 vs 1.29 mg/dL,p = 0.030 and 0.6 ± 0.4 vs 1.5 ± 0.9 mg/dL,p = 0.022, respectively) at 24 h after the procedure, and received fewer transfusions during the whole postoperative period (3 vs 9 red blood cell units (RBC),p = 0.017).

Conclusion

Our pilot study suggests that the use of magnetically levitated centrifugal pumps for extracorporeal circulation support is associated with a lower risk of hemolysis, though larger studies are warranted to confirm our results.
Application of three-dimensional reconstruction combined with dial positioning in small pulmonary nodules surgery
Authors: Zhao Long , Yang Wenyu , Hong Ruofeng , Fei Jianbin
Published: September 2021

Background

With the popularization of HRCT and VATS, the incidence of early stage lung cancer is increasing recent years. About 63% of small pulmonary nodules can not be accurately identified in VATS. We use 3-D reconstruction combined with dial positioning to analyze its accuracy and impact on patients undergoing VATS in our hospital.

Method

All patients underwent HRCT scanning and 3-D reconstruction preoperatively to determine the scope of surgery. The precise positional relationship between the nodule and the nearest rib must be recorded. Locate the plane of pulmonary nodule on CT, rotate the plane to make the affected side upwards, take the highest point of pleura as 12 o'clock on the dial, record the corresponding point of the nodule meticulously, mark the pulmonary nodule on the skin of the patient. A 18G indwelling needle was used to puncture through the marker into the visceral pleura. Electrocautery mark was made on the bleeding point of the lung surface. Then wedge resection or segmental resection was made.

Materials and result

From September 2019 to December 2020, 74 patients underwent VATS pulmonary nodule resection in our institute, with an average age of (56.4 ± 11.7) years old. A total of 83 nodules were resected in 74 patients, 23 nodules received segmentectomy and 60 nodules received wedge resection with 16 benign nodules and 67 malignant nodules. The distance between the nodules and pleura was (0–25) mm, with an average of (8.0 ± 3.9) mm. The target nodules were found in all patients, the positioning accuracy was 97.6%. All patients were satisfied with the positioning method, and there was no scar left at the skin puncture point after operation.

Conclusion

3-D reconstruction combined with dial positioning method can reduce patients' anxiety preoperatively, avoid various complications, reduce hospitalization expenses, and has an acceptable accuracy and short learning curve, which can be further promoted and applied in clinic.
Successful treatment of bilateral multiple pulmonary arteriovenous malformations in a patient with brain abscess and severe hypoxemia using a combination of transcatheter embolotherapy and surgical resection: a case report
Authors: Ochi Takahiro , Chiyo Masako , Ito Takamasa , Furumoto Hideharu , Sugiura Toshihiko , Saitoh Yukio
Published: September 2021

Background

A pulmonary arteriovenous malformation is an abnormal dilated blood vessel that makes direct communication between a pulmonary artery and pulmonary vein and can be associated with hypoxemia or neurological complications, including brain abscess and cerebral infarction. Treatment of pulmonary arteriovenous malformation includes surgical resection and transcatheter embolotherapy, however the adaptation of therapies should be considered when a patient is in bad condition.

Case presentation

A 51-year-old man was admitted after developing fever, consciousness disorder, and hypoxemia. Magnetic resonance imaging of the brain showed a brain abscess. Bilateral pulmonary arteriovenous malformations were found by contrast computed tomography. Because of a family history of pulmonary arteriovenous malformation, a history of epistaxis, and the existence of oral mucosa telangiectasia, he was diagnosed with hereditary hemorrhagic telangiectasia and brain abscess caused by intrapulmonary right-to-left shunt. The brain abscess improved with antibiotic treatment; however, the administration of oxygen did not ameliorate his hypoxemia. His hypoxemia was exacerbated by positive pressure ventilation. Considering his systemic and respiratory condition, we considered surgery to involve a high degree of risk. After controlling his brain abscess and pneumonia, transcatheter embolotherapy was performed. This improved his systemic condition, enabling surgical treatment.

Conclusions

This middle-aged patient suffering from brain abscess and severe hypoxemia with multiple pulmonary arteriovenous malformations was successfully treated by a combination of transcatheter embolotherapy and surgery. The adaptation and combination of therapies, as well as the sequence of treatments, should be considered depending on the patient status and lesions.
An assessment of the quality of care provided at primary health care centres in camps for internally displaced persons in Iraq in 2018
Authors: Khan Muhammad Fawad , Jeannetot Daniel , Olleri Kamal Sunil , Bakker Mirjam , Musani Altaf Sadrudin , Abdel Moneim Adham Rashad Ismail , Hatahit Wael , Zwanikken Prisca
Published: September 2021

Introduction

The humanitarian crisis in Iraq remains one of the largest and most unstable in the world. In 2014, over 2.5 million civilians were displaced in Iraq; between 2015 and 2017 more than 3 million people continued to be displaced. While health-related research concerning internally displaced persons (IDPs) population has been conducted in many settings, very few have looked at the quality of care delivered in primary health care centres (PHCC) inside camps. The objective of this operational research is to assess the quality of health care services at PHCC in operational IDP camps supported by local and international NGOs (humanitarian partners) as well as the Directorate of Health (DoH) in Iraq at baseline and after 6 months.

Method

A framework based on five components was used to assess quality of care by assigning a quality-of-care index score. Using a longitudinal design; data were collected through observations of facilities and of patient consultations, as well as health worker and patient exit interviews, in static PHCC in operational IDP camps of Iraq during two different phases: in June (n = 55), and December 2018 (n = 47). These facilities supported more than 500,000 IDPs. Descriptive and statistical analyses were conducted, and the results compared.

Result

For all camps (n = 47), the average overall quality of care index score increased between the two phases. No specific type of organisation consistently provided a better quality of care. The camp size was unrelated to the quality of care provided at the respective facility. The domain indicators “Client Care” and “Environment and Safety” mostly related to the variation in the general assessment of quality. Patient satisfaction was unrelated to any other domain score. Compared at 0 and after 6-months, the quality of care index score between the type of organisation and governorate showed that feedback positively impacted service delivery after the first assessment. Positive differences in scores also appeared, with notable improvements in Client care and Technical competence.

Conclusion

Humanitarian partners and the DoH are able to provide quality care, independent of camp size or the number of camps managed, and their cooperation can lead to quick improvements. This research also shows that quality of care assessment in emergency settings can be carried out in formal IDP camps using non-emergency standards.
HRAS is a therapeutic target in malignant chemo-resistant adenomyoepithelioma of the breast
Authors: Bièche Ivan , Coussy Florence , El-Botty Rania , Vacher Sophie , Château-Joubert Sophie , Dahmani Ahmed , Montaudon Elodie , Reyes Cécile , Gentien David , Reyal Fabien , Ricci Francesco , Nicolas André , Marchio Caterina , Vincent-Salomon Anne , Laé Marick , Marangoni Elisabetta
Published: September 2021

Malignant adenomyoepithelioma (AME) of the breast is an exceptionally rare form of breast cancer, with a significant metastatic potential. Chemotherapy has been used in the management of advanced AME patients, however the majority of treatments are not effective. Recent studies report recurrent mutations in the HRAS Q61 hotspot in small series of AMEs, but there are no preclinical or clinical data showing H-Ras protein as a potential therapeutic target in malignant AMEs. We performed targeted sequencing of tumours’ samples from new series of 13 AMEs, including 9 benign and 4 malignant forms. Samples from the breast tumour and the matched axillary metastasis of one malignant HRAS mutated AME were engrafted and two patient-derived xenografts (PDX) were established that reproduced the typical AME morphology. The metastasis-derived PDX was treated in vivo by different chemotherapies and a combination of MEK and BRAF inhibitors (trametinib and dabrafenib). All malignant AMEs presented a recurrent mutation in the HRAS G13R or G12S hotspot. Mutation of PIK3CA were found in both benign and malignant AMEs, while AKT1 mutations were restricted to benign AMEs. Treatment of the PDX by the MEK inhibitor trametinib, resulted in a marked anti-tumor activity, in contrast to the BRAF inhibitor and the different chemotherapies that were ineffective. Overall, these findings further expand on the genetic features of AMEs and suggest that patients carrying advanced HRAS-mutated AMEs could potentially be treated with MEK inhibitors.
Resistin levels and inflammatory and endothelial dysfunction markers in obese postmenopausal women with type 2 diabetes mellitus
Authors: Giandalia A. , Alibrandi A. , Giorgianni L. , Lo Piano F. , Consolo F. , Longo Elia G. , Asztalos B. , Cucinotta D. , Squadrito G. , Russo G. T.
Published: September 2021

Background

Obesity-associated coronary heart disease (CHD) risk is higher in women than in men with type 2 diabetes (T2DM). Resistin, an adipokine secreted by adispose tissue, may contribute to this higher risk.

Aims

To explore the relationships among resistin levels and common inflammatory and endothelial dysfunction markers and CHD risk in obese post-menopausal T2DM women.

Methods

Serum levels of resistin, hsCRP, IL-6, Soluble vascular cell adhesion molecule (sVCAM), homocysteine (tHcy), HOMA-IR and metabolic parameters were determined in a group of 132 T2DM women with and without documented CHD and in 55 non-diabetic women.

Results

Resistin, sVCAM, IL-6 and tHcy levels were comparable in T2DM and controls. CHD women showed higher resistin, sVCAM and tHcy levels than those without CHD, and for resistin this difference remained significant after age-adjustment (P = 0.013); conversely hsCRP were ~ 2X higher in T2DM women than in controls (P = 0.0132) without any difference according to CHD history. At univariate analysis resistin levels were significantly associated with age, waist circumference, hypertension, tHcy, hsPCR, sVCAM, IL-6, HDL-cholesterol, triglycerides and creatinine levels, but only creatinine, triglycerides, hsCRP, IL-6 and sVCAM were independently associated to resistin levels at stepwise regression analysis.

Resistin levels were independently associated to CHD, increasing the risk by 1.15 times (0.986–1.344 95% CI), together with age, tHcy, LDL-C and hypertension.

Conclusions

Circulating resistin levels were comparable in obese/overweight T2DM and control women. In T2DM women, resistin levels correlated with markers of renal function, systemic inflammation and endothelial dysfunction and were independently associated with a higher CHD risk.