bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of the health-related quality of life of end stage kidney disease patients on hemodialysis and non-hemodialysis management in Uganda
Authors: Bagasha Peace , Namukwaya Elizabeth , Leng Mhoira , Kalyesubula Robert , Mutebi Edrisa , Naitala Ronald , Katabira Elly , Petrova Mila
Published: April 2021

Background

Health-related quality of life is recognized as a key outcome in chronic disease management, including kidney disease. With no national healthcare coverage for hemodialysis, Ugandan patients struggle to pay for their care, driving families and communities into poverty. Studies in developed countries show that patients on hemodialysis may prioritize quality of life over survival time, but there is a dearth of information on this in developing countries. We therefore measured the quality of life (QOL) and associated factors in end stage renal disease (ESRD) patients in a major tertiary care hospital in Uganda.

Methods

Baseline QOL measurement in a longitudinal cohort study was undertaken using the Kidney Disease Quality of Life Short Form Ver 1.3. Patients were recruited from the adult nephrology unit if aged > 18 years with an estimated glomerular filtration rate ≤ 15mls/min/1,73m2. Clinical, demographic and micro-financial information was collected to determine factors associated with QOL scores.

Results

Three hundred sixty-four patients (364) were recruited, of whom 124 were on hemodialysis (HD) and 240 on non-hemodialysis (non-HD) management. Overall, 94.3% of participants scored less than 50 (maximum 100). Mean QOL scores were low across all three principal domains: physical health (HD: 33.14, non-HD: 34.23), mental health (HD: 38.01, non-HD: 38.02), and kidney disease (HD: 35.16, non-HD: 34.00). No statistically significant difference was found between the overall quality of life scores of the two management groups. Breadwinner status (p < 0.001), source of income (p0.026) and hemodialysis management type (p0.032) were the only factors significantly associated with QOL scores, and this was observed in the physical health and kidney disease principal domains only. No factors were significantly associated with scores for the mental health principal domain and/or overall QOL score.

Conclusion

The quality of life of Ugandan patients with ESRD has been found to be lower across all three domains of the Kidney Disease Quality of Life Short Form than reported anywhere in the world, with no difference observed between the non-HD and HD management groups. Interventions targeting all domains of QOL are needed among patients with ESRD in Uganda and, potentially, in other resource limited settings.
An Australian Neuro-Palliative perspective on Huntington's disease: a case report
Authors: Shah Rajvi , Lee Sarah CM , Strasser Rupert B , Grossman Christopher
Published: April 2021

Background

Huntington’s Disease (HD) is an incurable, progressive neuro-degenerative disease. For patients with HD access to palliative care services is limited, with dedicated Neuro-Palliative Care Services rare in Australia. We discuss the experiences of and benefits to a patient with late-stage HD admitted to our Neuro-Palliative Care service.

Case presentation

We present the case of a patient with a 16-year history of HD from time of initial genetic testing to admission to our Neuro-Palliative Care service with late-stage disease.

Conclusions

Given the prolonged, fluctuating and heterogenous HD trajectory, measures need to be implemented to improve earlier access to multi-specialty integrative palliative care services. Given the good outcomes of our case, we strongly advocate for the role of specialised Neuro-Palliative Care services to bridge the gap between clinical need and accessibility.
Changes in the prevalence and trends of female genital mutilation in Iraqi Kurdistan Region between 2011 and 2018
Authors: Shabila Nazar P.
Published: April 2021

Background

Female genital mutilation (FGM) is commonly practiced in Iraqi Kurdistan Region, where there are extensive efforts to combat the practice over the last decade. This study aimed to determine the trends and changes in the FGM prevalence in Iraq between 2011 and 2018 and assess their associated factors.

Methods

Secondary data analysis of the Iraq Multiple Indicator Cluster Survey 2011 and 2018 was carried out to calculate the prevalence and the relative changes in the prevalence of FGM for 2011 and 2018 by governorate. The change in the prevalence was compared with the changes in other exposure variables such as age, education level, wealth, and area of residence over the same period.

Results

The prevalence of FGM in 2018 was high in Erbil and Suleimaniya governorates (50.1% and 45.1%). The prevalence of FGM decreased remarkably from 2011 to 2018 in all governorates of the Iraqi Kurdistan Region. The decrease in the prevalence was statistically significant in Erbil and Suleimaniya. FGM prevalence declined remarkably in all age, education level, residence area groups, and most economic level groups. Such decline was associated with a significant increase in the education level, wealth, and urban residence. The decline was highest in the younger age groups, with a relative change of − 43.0% among 20–24 years and − 39.2% among 15–19 years. The decline was also highest in those with secondary and higher education (relative change = −32%). The decline was higher in rural areas than in urban areas (relative change = −35.3% and − 27.4%, respectively). The decline was higher among the poorest and second wealth quintile (relative change = −38.8% and − 27.2%, respectively).

Conclusion

The trend of FGM in Iraqi Kurdistan Region declined remarkably and significantly from 2011 to 2018. Further decline is predicted because of having lower rates and a higher decline in the younger age groups. However, the rates remained high in Erbil and Suleimaniya governorates that need further intensifying the preventive measures. The education level of women plays a primary role in decreasing the prevalence and should be considered in future efforts to ban the practice.
Pyosalpinx due to Cronobacter sakazakii in an elderly woman
Authors: Ohira Satoshi , Ikeda Eri , Kamijo Kyosuke , Nagai Tomokuni , Tsunemi Koji , Uchiyama Natsuki , Matsubara Naoki , Tachibana Ryota
Published: April 2021

Background

Cronobacter sakazakii (C. sakazakii) is a bacterium known to cause severe neonatal infections in premature infants with the consumption of contaminated powdered milk formula. Adult infections are rare, and there have been no reports of pyosalpinx due to C. sakazakii to date.

Case presentation

We report a case of left pyosalpinx due to C. sakazakii in a sexually inactive postmenopausal woman. A 70-year-old woman presented to our hospital with left lower abdominal pain and fever. Abdominal computed tomography disclosed a cystic mass continuous with the left edge of the uterus. Urgent laparotomy revealed a ruptured left pyosalpinx with pus-like content. Left salpingo-oophorectomy, resection of the right tube, and washing of the abdominal cavity with saline were performed. Pathological examination of the left adnexa showed tubal tissue with acute inflammation and inflammatory exudate, which were compatible with pyosalpinx, and pus culture yielded C. sakazakii.

Conclusions

This is the first case report of pyosalpinx due to C. sakazakii. Cronobacter sakazakii infections in adult women might occur in the elderly, whose immunity has weakened. Further accumulation of cases of C. sakazakii infection is needed to clarify the etiology and behavior of C. sakazakii in adults.
The use of herbal and dietary supplement among community-dwelling elderly in a suburban town of Malaysia
Authors: Wahab Mohd Shahezwan Abd , Zaini Muhammad Helmi , Ali Aida Azlina , Sahudin Shariza , Mehat Muhammad Zulfadli , Hamid Hafizah Abdul , Mustaffa Mohd Faiz , Othman Noordin , Maniam Sandra
Published: April 2021

Background

The use of herbal and dietary supplement (HDS) in health and disease management has gained global attention. HDS are generally accepted by the public and are associated with positive health behaviours. However, several reports have been documented with regards to their potential adverse effects and interaction with conventional medicines. Limited data is currently available on the use of HDS among elderly population in Malaysia. This present study aims to investigate the prevalence of and pattern of HDS use among a sample of community-dwelling elderly in a suburban town in Malaysia.

Methods

A cross-sectional survey was conducted between March and May 2019 among the elderly aged ≥60 years old. The participants with the following criteria were included in the study: aged ≥60 years, residing in Puncak Alam and able to understand Malay or English language. Data were collected using a pre-validated questionnaire. All statistical analysis was conducted using IBM SPSS ver. 23.

Results

Overall, 336 out of 400 elderly responded to the survey, achieving a response rate of 84%. This study observed that almost 50% of the respondents were using at least one type of HDS in the past one month of the survey. Among HDS non-users, most of them preferred to use modern medicines (62.6%, 114/182). Among the HDS users, 75.3% (116/154) were using at least one type of modern medicine (prescription or over-the-counter medicine). Multivariate analysis showed that having good to excellent perceived health (adjusted OR = 2.666, 95% CI = 1.592–4.464), having felt sick at least once in the past one month (adjusted OR = 2.500, 95% CI = 1.426–4.383), and lower body mass index (adjusted OR = 0.937, 95% CI = 0.887–0.990) were associated with HDS use. It was noted that only a small percentage of HDS users (16.2%, 25/154) had informed healthcare providers on their HDS use.

Conclusion

The use of HDS is common among the elderly sampled. Hence, healthcare providers should be more vigilant in seeking information of HDS use for disease management in their elderly patients. Campaigns that provide accurate information regarding the appropriate use of HDS among the elderly are pertinent to prevent misinformation of the products.
Affective and cognitive components of students’ attitudes towards communication learning - validation of the Communication Skills Attitude Scale in a cohort of polish medical students
Authors: Przymuszała Piotr , Cerbin-Koczorowska Magdalena , Marciniak-Stępak Patrycja , Zielińska-Tomczak Łucja , Piszczek Martyna , Jasiński Jan , Marciniak Ryszard
Published: April 2021

Background

The Communication Skills Attitude Scale (CSAS) is a recognized tool for assessment of attitudes towards communication learning. In the original version, it consists of 26 items divided on theoretical assumptions into two subscales: Positive and Negative Attitudes Scales. However, the evidence for its structure seems unsatisfactory, and a simple division into positive and negative attitudes may be insufficient to describe attitudes of medical students towards communication learning. Moreover, the existing evidence of the test-retest reliability of the CSAS seems limited. Consequently, this study aimed to provide more evidence on its psychometric properties while validating the CSAS questionnaire in a cohort of Polish medical students.

Methods

The CSAS was translated, adapted into Polish, and validated in a cohort of 389 Polish medical students. Statistical analysis involved, among others, parallel analysis to determine the number of factors, confirmatory factor analysis to compare the proposed model with theory-based ones, and test-retest reliability analysis.

Results

Conducted analysis revealed that in the examined population, the CSAS should rather consist of four than two subscales. Proposed four subscales addressed perceived outcomes of communication learning, positive and negative attitudes towards it (affective components), and factors motivating students to learn communication (a cognitive component of attitudes). Results of test-retest reliability were satisfactory for individual items and subscales.

Conclusions

This study presented a valid and reliable version of the Communication Skills Attitude Scale for Polish medical students and confirmed previous assumptions that CSAS may also be appropriate for assessment of affective and cognitive components of attitudes. Future research should, based on Ajzen’s Theory of Planned Behavior, make attempts to develop a tool assessing not only attitudes but also subjective norms and perceived behavioral control.
What does it take to consent to islet cell xenotransplantation?: Insights from an interview study with type 1 diabetes patients and review of the literature
Authors: Kögel Johannes , Thiersch Sandra , Ludwig Barbara , Seissler Jochen , Marckmann Georg
Published: April 2021

Background

The transplantation of porcine islet cells provides a new potential therapy to treat patients with type 1 diabetes mellitus (T1DM). Compared to other biomedical technologies, xenotransplantation stands out in terms of its involvement of animals as graft sources, as well as the possible transmission of infectious diseases. As these aspects are especially relevant for potential xenotransplantation recipients, it is important to assess their opinion regarding this technology, in particular in terms of the requirements that should be met in the informed consent process for xenotransplantation.

Methods

We conducted qualitative interviews with seven T1DM patients to assess their information needs prior to xenotransplantation. Before the interview, the participants received a model informed consent form for a clinical trial with porcine islet cells transplantation. The interviews were transcribed and analysed using qualitative content analysis.

Results

In the interviews, we identified several requirements that are crucial for patients with T1DM in order to consider xenotransplantation as a potential treatment option: therapy-related requirements, professional care and supervision, successful behaviour and attitude management, improving quality of life, and managing control/self-determination challenges. Regarding the informed consent form, several of the participants’ questions remained open and should be addressed in more detail. The interviewees stressed the importance of personal consultations.

Conclusions

To become a sustainable therapeutic option, patients especially expected an improved diabetes control and a reduction of diabetes-related burdens. Health-related aspects prove to be pivotal for diabetic patients when considering porcine islet cell transplantation. The use of pigs as source for organ retrievals was not considered as problematic.
Moving from “let’s fix them” to “actually listen”: the development of a primary care intervention for mental-physical multimorbidity
Authors: McKenzie Kylie J. , Fletcher Susan L. , Pierce David , Gunn Jane M.
Published: April 2021

Background

Effective person-centred interventions are needed to support people living with mental-physical multimorbidity to achieve better health and wellbeing outcomes. Depression is identified as the most common mental health condition co-occurring with a physical health condition and is the focus of this intervention development study. The aim of this study is to identify the key components needed for an effective intervention based on a clear theoretical foundation, consideration of how motivational interviewing can inform the intervention, clinical guidelines to date, and the insights of primary care nurses.

Methods

A multimethod approach to intervention development involving review and integration of the theoretical principles of Theory of Planned Behavior and the patient-centred clinical skills of motivational interviewing, review of the expert consensus clinical guidelines for multimorbidity, and incorporation of a thematic analysis of group interviews with Australian nurses about their perspectives of what is needed in intervention to support people living with mental-physical multimorbidity.

Results

Three mechanisms emerged from the review of theory, guidelines and practitioner perspective; the intervention needs to actively ‘engage’ patients through the development of a collaborative and empathic relationship, ‘focus’ on the patient’s priorities, and ‘empower’ people to make behaviour change.

Conclusion

The outcome of the present study is a fully described primary care intervention for people living with mental-physical multimorbidity, with a particular focus on people living with depression and a physical health condition. It builds on theory, expert consensus guidelines and clinician perspective, and is to be tested in a clinical trial.
CREB-dependent LPA-induced signaling initiates a pro-fibrotic feedback loop between small airway basal cells and fibroblasts
Authors: Nathan Shyam , Zhang Haijun , Andreoli Mirko , Leopold Philip L. , Crystal Ronald G.
Published: April 2021

Background

Lysophosphatidic acid (LPA), generated extracellularly by the action of autotaxin and phospholipase A2, functions through LPA receptors (LPARs) or sphingosine-1-phosphate receptors (S1PRs) to induce pro-fibrotic signaling in the lower respiratory tract of patients with idiopathic pulmonary fibrosis (IPF). We hypothesized that LPA induces changes in small airway epithelial (SAE) basal cells (BC) that create cross-talk between the BC and normal human lung fibroblasts (NHLF), enhancing myofibroblast formation.

Methods

To assess LPA-induced signaling, BC were treated with LPA for 2.5 min and cell lysates were analyzed by phosphokinase array and Western blot. To assess transcriptional changes, BC were treated with LPA for 3 h and harvested for collection and analysis of RNA by quantitative polymerase chain reaction (qPCR). To assess signaling protein production and function, BC were washed thoroughly after LPA treatment and incubated for 24 h before collection for protein analysis by ELISA or functional analysis by transfer of conditioned medium to NHLF cultures. Transcription, protein production, and proliferation of NHLF were assessed.

Results

LPA treatment induced signaling by cAMP response element-binding protein (CREB), extracellular signal-related kinases 1 and 2 (Erk1/2), and epithelial growth factor receptor (EGFR) resulting in elevated expression of connective tissue growth factor (CTGF), endothelin-1 (EDN1/ET-1 protein), and platelet derived growth factor B (PDGFB) at the mRNA and protein levels. The conditioned medium from LPA-treated BC induced NHLF proliferation and increased NHLF expression of collagen I (COL1A1), smooth muscle actin (ACTA2), and autotaxin (ENPP2) at the mRNA and protein levels. Increased autotaxin secretion from NHLF correlated with increased LPA in the NHLF culture medium. Inhibition of CREB signaling blocked LPA-induced changes in BC transcription and translation as well as the pro-fibrotic effects of the conditioned medium on NHLF.

Conclusion

Inhibition of CREB signaling may represent a novel target for alleviating the LPA-induced pro-fibrotic feedback loop between SAE BC and NHLF.
Prognostic role of MUC5B rs35705950 genotype in patients with idiopathic pulmonary fibrosis (IPF) on antifibrotic treatment
Authors: Biondini Davide , Cocconcelli Elisabetta , Bernardinello Nicol , Lorenzoni Giulia , Rigobello Chiara , Lococo Sara , Castelli Gioele , Baraldo Simonetta , Cosio Manuel G. , Gregori Dario , Saetta Marina , Balestro Elisabetta , Spagnolo Paolo
Published: April 2021

Background

A common variant located in the promoter region of MUC5B (rs35705950) is the strongest risk factor for sporadic and familiar IPF, as well as a predictor of outcome. However, there are no data on the effect of MUC5B rs35705950 genotype on the prognosis of IPF patients on antifibrotic treatment. The aim of this study is to determine, in a phenotypically well-characterized population of patients with IPF treated with antifibrotics, the impact of MUC5B rs35705950 genotype on disease progression and survival.

Methods

88 IPF patients on antifibrotic treatment were followed-up from 2014 until transplantation, death or end of follow-up (December 2019). Disease progression was defined as a forced vital capacity (FVC) loss ≥ 5% per year. All patients were genotyped for MUC5B rs35705950 by PCR amplification and Sanger sequencing.

Results

Out of 88 patients, 61 (69%) carried the mutant T allele (TT or TG) and 27 (31%) did not (GG). Carriage of the MUC5B rs35705950 T allele was not associated with a faster decline in FVC. Conversely, at the end of the follow-up, overall survival in carriers of the TT/TG genotype was longer compared to that of the GG genotype carriers. FVC (L) at baseline and time to respiratory failure at rest were independent predictors of worse prognosis.

Conclusions

In IPF patients on antifibrotic treatment, carriage of the MUC5B rs35705950 T allele is associated with longer survival, highlighting the usefulness of MUC5B genetic data in clinical decision making.
Macrophages-derived exosomal lncRNA LIFR-AS1 promotes osteosarcoma cell progression via miR-29a/NFIA axis
Authors: Zhang Hongliang , Yu Yiyang , Wang Jun , Han Yu , Ren Tingting , Huang Yi , Chen Chenglong , Huang Qingshan , Wang Wei , Niu Jianfang , Lou Jingbing , Guo Wei
Published: April 2021

Background

Osteosarcoma (OS) is the most common primary malignant bone tumor in young people. Tumor-associated macrophages (TAMs) have been reported to play an important role in the development of osteosarcoma. However, the detailed molecular mechanisms remain largely unknown and need to be elucidated. Recently, exosomes have been reported as the crucial mediator between tumor cells and the tumor microenvironment. And a lot of lncRNAs have been reported to act as either oncogenes or tumor suppressors in osteosarcoma. In this research, we aim to explore the role of macrophages-derived exosomal lncRNA in osteosarcoma development and further elucidated the potential molecular mechanisms involved.

Methods

TAMs were differentiated from human mononuclear cells THP-1, and a high-throughput microarray assay was used to analyze the dysregulated lncRNAs and miRNAs in osteosarcoma cells co-cultured with macrophages-derived exosomes. Western blot, qRT-PCR assays, and Dual-luciferase reporter assay were used to verify the interaction among LIFR-AS1, miR-29a, and NFIA. Cck-8, EdU, colony formation assay, wound-healing, and transwell assay were performed to explore the characterize the proliferation and metastasis ability of OS cells. And qPCR, Western blots, immunohistochemistry, and cell immunofluorescence were used to detect the expression of relative genes or proteins.

Results

In this study, we found that THP-1-induced macrophage-derived exosomes could facilitate osteosarcoma cell progression both in vitro and in vivo. Then, the results of the high-throughput microarray assay showed that LIFR-AS1 was highly expressed and miR-29a was lowly expressed. Furthermore, LIFR-AS1 was identified as a miR-29a sponge, and NFIA was validated as a direct target of miR-29a. Functional assays demonstrated that knockdown of exosomal LIFR-AS1 could attenuate the promotion effects of macrophages-derived exosomes on osteosarcoma cell progression and miR-29a inhibition could reserve the effect of LIFR-AS1-knockdown exosomes. Correspondingly, NFIA-knockdown could partially reverse the tumor inhibition effect of miR-29a on osteosarcoma cells.

Conclusions

Taken together, macrophages-derived exosomal lncRNA LIFR-AS1 can promote osteosarcoma cell proliferation, invasion, and restrain cell apoptosis via miR-29a/NFIA axis, which can act as a potential novel therapeutic target for osteosarcoma therapy.
Immunological significance of prognostic alternative splicing signature in hepatocellular carcinoma
Authors: Xu Qianhui , Xu Hao , Deng Rongshan , Li Nanjun , Mu Ruiqi , Qi Zhixuan , Shen Yunuo , Wang Zijie , Wen Jingchao , Zhao Jiaxin , Weng Di , Huang Wen
Published: April 2021

Background

Hepatocellular carcinoma (HCC) ranks the sixth prevalent tumors with high mortality globally. Alternative splicing (AS) drives protein diversity, the imbalance of which might act an important factor in tumorigenesis. This study aimed to construct of AS-based prognostic signature and elucidate the role in tumor immune microenvironment (TIME) and immunotherapy in HCC.

Methods

Univariate Cox regression analysis was performed to determine the prognosis-related AS events and gene set enrichment analysis (GSEA) was employed for functional annotation, followed by the development of prognostic signatures using univariate Cox, LASSO and multivariate Cox regression. K-M survival analysis, proportional hazards model, and ROC curves were conducted to validate prognostic value. ESTIMATE R package, ssGSEA algorithm and CIBERSORT method and TIMER database exploration were performed to uncover the context of TIME in HCC. Quantitative real-time polymerase chain reaction was implemented to detect ZDHHC16 mRNA expression. Cytoscape software 3.8.0 were employed to visualize AS-splicing factors (SFs) regulatory networks.

Results

A total of 3294 AS events associated with survival of HCC patients were screened. Based on splicing subtypes, eight AS prognostic signature with robust prognostic predictive accuracy were constructed. Furthermore, quantitative prognostic nomogram was developed and exhibited robust validity in prognostic prediction. Besides, the consolidated signature was significantly correlated with TIME diversity and ICB-related genes. ZDHHC16 presented promising prospect as prognostic factor in HCC. Finally, the splicing regulatory network uncovered the potential functions of splicing factors (SFs).

Conclusion

Herein, exploration of AS patterns may provide novel and robust indicators (i.e., risk signature, prognostic nomogram, etc.,) for prognostic prediction of HCC. The AS-SF networks could open up new approach for investigation of potential regulatory mechanisms. And pivotal players of AS events in context of TIME and immunotherapy efficiency were revealed, contributing to clinical decision-making and personalized prognosis monitoring of HCC.
Efficacy and safety of dihydroartemisinin–piperaquine versus artemether–lumefantrine for treatment of uncomplicated Plasmodium falciparum malaria in Ugandan children: a systematic review and meta-analysis of randomized control trials
Authors: Assefa Dawit Getachew , Zeleke Eden Dagnachew , Bekele Delayehu , Tesfahunei Hanna Amanuel , Getachew Emnet , Joseph Michele , Manyazewal Tsegahun
Published: April 2021

Background

The emergence of artemisinin resistance in Southeast Asia andPlasmodium falciparum kelch13propeller gene mutations in sub-Saharan African pose the greatest threat to global efforts to control malaria. This is a critical concern in Uganda, where artemisinin-based combination therapy (ACT) is the first-line treatment for uncomplicated falciparum. The objective of this study was to compare the efficacy and safety of dihydroartemisinin–piperaquine (DHA–PQ) and artemether–lumefantrine (AL) for the treatment of uncomplicated falciparum malaria in Ugandan children.

Methods

A search of PubMed and the Cochrane Central Register of Controlled Trials for retrieving randomized controlled trials comparing the efficacy and safety of DHA–PQ and AL for treatment of uncomplicated falciparum malaria in Ugandan children was done. The search was performed up to 31 August 2020. The data extracted from eligible studies and pooled as risk ratio (RR) with a 95% confidence interval (CI), using Rev Man Software (5.4). The protocol was registered in PROSPERO, ID: CRD42020182354.

Results

Eleven trials were included in this review and two of them only included under safety outcome. Total 3798 participants were enrolled. The PCR unadjusted treatment failure was significantly lower with DHA–PQ at day 28 (RR 0.30, 95% CI 0.19–0.49; participants = 7863; studies = 5; I2 = 93%, low quality evidence) and at day 42 (RR 0.53, 95% CI 0.38–0.76; participants = 1618; studies = 4; I2 = 79%, moderate quality of evidence). The PCR adjusted treatment failure at day 42 was significantly lower with DHA–PQ treatment group (RR 0.45, 95% CI 0.28 to 0.72; participants = 1370; studies = 5, high quality of evidence), and it was below 5% in both arms at day 28 (moderate quality of evidence). AL showed a longer prophylactic effect on new infections which may last for up to 63 days (PCR-adjusted treatment failure: RR 2.04, 95% CI 1.13–3.70; participants = 1311; studies = 2, moderate quality of evidence). Compared to AL, DHA–PQ was associated with a slightly higher frequency of cough (RR 1.07, 95% CI 1.01 to 1.13; 2575 participants; six studies; high quality of evidence). In both treatment groups, the risk of recurrent parasitaemia due to possible recrudescence was less than 5% at day 28. The appearance of gametocyte between 29 and 42 days was also significantly lower in DHA–PQ than AL (RR 0.26, 95% CI 0.12 to 0.56; participants = 623; studies = 2; I2 = 0%).

Conclusion

Compared to AL, DHA–PQ appeared to reduce treatment failure and gametocyte carriage in Ugandan children. This may trigger DHA–PQ to become the first-line treatment option. Both treatments were safe and well-tolerated.
Asthmatic condition induced the activity of exosome secretory pathway in rat pulmonary tissues
Authors: Almohammai Asheed , Rahbarghazi Reza , Keyhanmanesh Rana , Rezaie Jafar , Ahmadi Mahdi
Published: April 2021

Background

The recent studies highlighted the critical role of exosomes in the regulation of inflammation. Here, we investigated the dynamic biogenesis of the exosomes in the rat model of asthma.

Results

Our finding showed an increase in the expression of IL-4 and the suppression of IL-10 in asthmatic lung tissues compared to the control samples (p < 0.05). Along with the promotion of IL-4, the protein level of TNF-α was induced, showing an active inflammatory status in OVA-sensitized rats. According to our data, the promotion of asthmatic responses increased exosome biogenesis indicated by increased CD63 levels and acetylcholine esterase activity compared to the normal condition (p < 0.05).

Conclusion

Data suggest that the stimulation of inflammatory response in asthmatic rats could simultaneously increase the paracrine activity of pulmonary cells via the exosome biogenesis. Exosome biogenesis may correlate with the inflammatory response.
Biomedical applications of 2D monoelemental materials formed by group VA and VIA: a concise review
Authors: Gao Ping , Xiao Yufen , YuliangWang  , Li Leijiao , Li Wenliang , Tao Wei
Published: April 2021

The development of two-dimensional (2D) monoelemental nanomaterials (Xenes) for biomedical applications has generated intensive interest over these years. In this paper, the biomedical applications using Xene-based 2D nanomaterials formed by group VA (e.g., BP, As, Sb, Bi) and VIA (e.g., Se, Te) are elaborated. These 2D Xene-based theranostic nanoplatforms confer some advantages over conventional nanoparticle-based systems, including better photothermal conversion, excellent electrical conductivity, and large surface area. Their versatile and remarkable features allow their implementation for bioimaging and theranostic purposes. This concise review is focused on the current developments in 2D Xenes formed by Group VA and VIA, covering the synthetic methods and various biomedical applications. Lastly, the challenges and future perspectives of 2D Xenes are provided to help us better exploit their excellent performance and use them in practice.
Correction to: Health-related quality of life in nonvalvular atrial fibrillation patients with controlled or uncontrolled anticoagulation status
Authors:   the REQUOL Study Group, Varona José Felipe , Seguí‑Ripoll José Miguel , Lozano‑Duran Cristina , Cuadrado‑Gómez Luis Miguel , Montagud‑Moncho Juan Bautista , Ramos‑Guerrero Antonio , Mirete‑Ferrer José Carlos , Donado Esther , García‑Alegría Javier
Published: April 2021

An amendment to this paper has been published and can be accessed via the original article.
Lessons from the pandemic on the value of research infrastructure
Authors: Roope Laurence S. J. , Candio Paolo , Kiparoglou Vasiliki , McShane Helen , Duch Raymond , Clarke Philip M.
Published: April 2021

The COVID-19 pandemic has shed a spotlight on the resilience of healthcare systems, and their ability to cope efficiently and effectively with unexpected crises. If we are to learn one economic lesson from the pandemic, arguably it is the perils of an overfocus on short-term allocative efficiency at the price of lack of capacity to deal with uncertain future challenges. In normal times, building spare capacity with ‘option value’ into health systems may seem inefficient, the costs potentially exceeding the benefits. Yet the fatal weakness of not doing so is that this can leave health systems highly constrained when dealing with unexpected, but ultimately inevitable, shocks—such as the COVID-19 pandemic. In this article, we argue that the pandemic has highlighted the potentially enormous option value of biomedical research infrastructure. We illustrate this with reference to COVID-19 response work supported by the United Kingdom National Institute for Health Research Oxford Biomedical Research Centre. As the world deals with the fallout from the most serious economic crisis since the Great Depression, pressure will soon come to review government expenditure, including research funding. Developing a framework to fully account for option value, and understanding the public appetite to pay for it, should allow us to be better prepared for the next emerging problem.
Perspectives of individuals with chronic spinal cord injury following novel balance training involving functional electrical stimulation with visual feedback: a qualitative exploratory study
Authors: Houston David J. , Unger Janelle , Lee Jae W. , Masani Kei , Musselman Kristin E.
Published: April 2021

Background

Individuals with an incomplete spinal cord injury (iSCI) are highly susceptible to falls during periods of walking or standing. We recently reported the findings of a novel intervention combining functional electrical stimulation with visual feedback balance training (FES + VFBT) on standing balance abilities among five individuals with motor iSCI. However, the previous publication did not report the perceived impact of the intervention on the participants’ lives. In this report, the experiences of these five individuals with incomplete spinal cord injury (iSCI) who had recently completed the four-week balance training program are described.

Methods

Five individuals with a motor iSCI took part in this study. Each individual was at least 12 months post-injury, capable of unassisted standing for 60 s and had a Berg Balance Scale Score < 46. Participants completed twelve sessions of a novel balance intervention combining closed-loop functional electrical stimulation with visual feedback balance training (FES + VFBT). Participants received visual feedback regarding their centre of pressure position as they completed balance-training exercises while FES was applied to the ankle plantarflexors and dorsiflexors bilaterally. Semi-structured interviews were conducted after completion of the balance training intervention and eight-weeks post-training to understand participant’s experiences. Categories and themes were derived from the transcripts using conventional content analysis.

Results

Three themes were identified from the collected transcripts: (1) Perceived benefits across International Classification of Functioning, Disability and Health levels; (2) Change in perceived fall risk and confidence; (3) Motivation to keep going.

Conclusions

Participation in the FES + VFBT program resulted in perceived benefits that led to meaningful improvements in activities of daily living. Following completion of the training, individuals felt they still had the capacity to improve. Individuals felt they had increased their balance confidence, while a few participants also reported a decrease in their risk of falling. The inclusion of qualitative inquiry allows for the evaluation of the meaningfulness of an intervention and its perceived impact on the lives of the participants.

Trial registration: NCT04262414 (retrospectively registered February 10, 2020)
Direction and magnitude of cerebrospinal fluid flow vary substantially across central nervous system diseases
Authors: Eide Per Kristian , Valnes Lars Magnus , Lindstrøm Erika Kristina , Mardal Kent-Andre , Ringstad Geir
Published: April 2021

Background

Several central nervous system diseases are associated with disturbed cerebrospinal fluid (CSF) flow patterns and have typically been characterized in vivo by phase-contrast magnetic resonance imaging (MRI). This technique is, however, limited by its applicability in space and time. Phase-contrast MRI has yet to be compared directly with CSF tracer enhanced imaging, which can be considered gold standard for assessing long-term CSF flow dynamics within the intracranial compartment.

Methods

Here, we studied patients with various CSF disorders and compared MRI biomarkers of CSF space anatomy and phase-contrast MRI at level of the aqueduct and cranio-cervical junction with dynamic intrathecal contrast-enhanced MRI using the contrast agent gadobutrol as CSF tracer. Tracer enrichment of cerebral ventricles was graded 0–4 by visual assessment. An intracranial pressure (ICP) score was used as surrogate marker of intracranial compliance.

Results

The study included 94 patients and disclosed marked variation of CSF flow measures across disease categories. The grade of supra-aqueductal reflux of tracer varied, with strong reflux (grades 3–4) in half of patients. Ventricular tracer reflux correlated with stroke volume and aqueductal CSF pressure gradient. CSF flow in the cerebral aqueduct was retrograde (from 4th to 3rd ventricle) in one third of patients, with estimated CSF net flow volume about 1.0 L/24 h. In the cranio-cervical junction, net flow was cranially directed in 78% patients, with estimated CSF net flow volume about 4.7 L/24 h.

Conclusions

The present observations provide in vivo quantitative evidence for substantial variation in direction and magnitude of CSF flow, with re-direction of aqueductal flow in communicating hydrocephalus, and significant extra-cranial CSF production. The grading of ventricular reflux of tracer shows promise as a clinical useful method to assess CSF flow pattern disturbances in patients.

Graphic abstract
Cochlea sparing optimized radiotherapy for nasopharyngeal carcinoma
Authors: Lamaj Enkelejda , Vu Erwin , van Timmeren Janita E. , Leonardi Chiara , Marc Louise , Pytko Izabela , Guckenberger Matthias , Balermpas Panagiotis
Published: April 2021

Background

Definitive chemoradiotherapy (CRT) is standard of care for nasopharyngeal carcinoma. Due to the tumor localization and concomitant platinum-based chemotherapy, hearing impairment is a frequent complication, without defined dose-threshold. In this study, we aimed to achieve the maximum possible cochleae sparing.

Materials and methods

Treatment plans of 20 patients, treated with CRT (6 IMRT and 14 VMAT) based on the QUANTEC organs-at-risk constraints were investigated. The cochleae were re-delineated independently by two radiation oncologists, whereas target volumes and other organs at risk (OARs) were not changed. The initial plans, aiming to a mean cochlea dose < 45 Gy, were re-optimized with VMAT, using 2–2.5 arcs without compromising the dose coverage of the target volume. Mean cochlea dose, PTV coverage, Homogeneity Index, Conformity Index and dose to other OAR were compared to the reference plans. Wilcoxon signed-rank test was used to evaluate differences, a p value < 0.05 was considered significant.

Results

The re-optimized plans achieved a statistically significant lower dose for both cochleae (median dose for left and right 14.97 Gy and 18.47 Gy vs. 24.09 Gy and 26.05 Gy respectively, p < 0.001) compared to the reference plans, without compromising other plan quality parameters. The median NTCP for tinnitus of the most exposed sites was 11.3% (range 3.52–91.1%) for the original plans, compared to 4.60% (range 1.46–90.1%) for the re-optimized plans (p < 0.001). For hearing loss, the median NTCP of the most exposed sites could be improved from 0.03% (range 0–99.0%) to 0.00% (range 0–98.5%, p < 0.001).

Conclusions

A significantly improved cochlea sparing beyond current QUANTEC constraints is feasible without compromising the PTV dose coverage in nasopharyngeal carcinoma patients treated with VMAT. As there appears to be no threshold for hearing toxicity after CRT, this should be considered for future treatment planning.
Clinical and echocardiographic trends in percutaneous balloon mitral valvuloplasty
Authors: Koren Ofir , Israeli Asaf , Rozner Ehud , Darawshy Nassem , Turgeman Yoav
Published: April 2021

Background

The prevalence of Rheumatic Mitral Stenosis (MS) has significantly changed over the last decades. We intend to examine patient demographics, Echocardiographic characteristics, procedural success rates, and complications throughout 30-years.

Methods

We conducted a single-center descriptive observational study. The study population consists of patients undergone percutaneous balloon mitral valvuloplasty (PBMV) at Emek Medical Center in Israel from January 1990 to May 2019.

Results

Four hundred seventeen patients underwent PBMV during the study period and were eligible for the study. Age did not change significantly over time (p = 0.09). The prevalence of Male and patients who were smoking and had multiple comorbidities such as hypertension, dyslipidemia, ischemic heart disease, and chronic kidney disease became increases over time (p = 0.02, p = 0.02, p = 0.001, p = 0.01, p = 0.02, and p = 0.001, respectively). Wilkins score and all its components increased over time, and the total score was higher in females (p = 0.01). Seventy-nine (18.9%) patients had complications. The rate of complications did not change over decades. Patients with Wilkins score > 8, post-procedural MR of ≥2, and post-procedural MVA < 1.5 had the highest risk for the need of Mitral valve replacement (MVR) surgery in 2 years following PBMV (3.64, 4.03, 2.44, respectively, CI 95%, p < .0001 for all). The median time in these patients was 630 days compared to 4–5 years in the entire population. Patients with Post-procedural MR of ≥2 and post-procedural MVA < 1.5 had ten times risk for developing heart failure (HR 9.07 and 10.06, respectively, CI 95%, P < .0001).

Conclusion

Our research reveals trends over time in patients’ characteristics and echocardiographic features. Our study population consists of more male patients with multiple comorbidities and more complex and calcified valvular structures in the last decade. Wilkins score > 8, post-procedural MR of ≥2, and post-procedural MVA < 1.5 cm2 were in-depended predictors for the time for surgery and heart failure hospitalization.
The role of the circadian clock in cancer hallmark acquisition and immune-based cancer therapeutics
Authors: Cash Elizabeth , Sephton Sandra , Woolley Cassandra , Elbehi Attia M. , R. I. Anu , Ekine-Afolabi Bene , Kok Victor C.
Published: April 2021

The circadian system temporally regulates physiology to maintain homeostasis. Co-opting and disrupting circadian signals appear to be distinct attributes that are functionally important for the development of a tumor and can enable or give rise to the hallmarks that tumors use to facilitate their initiation, growth and progression. Because circadian signals are also strong regulators of immune cell proliferation, trafficking and exhaustion states, they play a role in how tumors respond to immune-based cancer therapeutics. While immuno-oncology has heralded a paradigm shift in cancer therapeutics, greater accuracy is needed to increase our capability of predicting who will respond favorably to, or who is likely to experience the troubling adverse effects of, immunotherapy. Insights into circadian signals may further refine our understanding of biological determinants of response and help answer the fundamental question of whether certain perturbations in circadian signals interfere with the activity of immune checkpoint inhibitors. Here we review the body of literature highlighting circadian disruption as a cancer promoter and synthesize the burgeoning evidence suggesting circadian signals play a role in how tumors respond to immune-based anti-cancer therapeutics. The goal is to develop a framework to advance our understanding of the relationships between circadian markers, cancer biology, and immunotherapeutics. Bolstered by this new understanding, these relationships may then be pursued in future clinical studies to improve our ability to predict which patients will respond favorably to, and avoid the adverse effects of, traditional and immune-based cancer therapeutics.
Cyclosporine A-related neurotoxicity after haploidentical hematopoietic stem cell transplantation in children with hematopathy
Authors: Wang Yong , Zheng Yongzhi , Wen Jingjing , Ren Jinhua , Yuan Xiaohong , Yang Ting , Hu Jianda
Published: April 2021

Background

To evaluate cyclosporine A (CSA)-related neurotoxicity after haploidentical hematopoietic stem cell transplantation (HID-HSCT) in children with hematopathy.

Methods

This retrospective case series study included children with hematopathy who underwent HID-HSCT at Fujian Medical University Union Hospital between February 2013 and January 2017.

Results

Fifty-one children (39 males) were included in the study with a median age of 8 (range, 1.1–18) years. Seven patients (13.7%) developed CSA-related neurotoxicity after a median 38 (range, − 3 to 161) days from HID-HSCT. Hypertension (5/7, 71%) was the most common prodrome. Brain magnetic resonance imaging showed posterior reversible encephalopathy syndrome in six patients and atypical abnormalities in one patient. One patient died from grade IV graft-versus-host disease (GvHD) on day + 160, and six patients were alive at the last follow-up. Four patients (71.4%) achieved complete remission, while two patients developed secondary epilepsy and exhibited persistent MRI and electroencephalogram abnormalities at the 5-year follow-up. Hypertension after CSA was more common in patients with CSA-related neurotoxicity than in those without (71% vs. 11%, P = 0.002). Five-year overall survival did not differ significantly between patients with CSA-related neurotoxicity (85.7 ± 13.2%) and those without (65.8 ± 7.2%).

Conclusions

The incidence of CSA-related neurotoxicity in children with hematopathy undergoing HID-HSCT is relatively high.