bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic incorporation of prior knowledge from multiple domains in biomarker discovery
Authors: Guan Xin , Runger George , Liu Li
Published: March 2020

Background

In biomarker discovery, applying domain knowledge is an effective approach to eliminating false positive features, prioritizing functionally impactful markers and facilitating the interpretation of predictive signatures. Several computational methods have been developed that formulate the knowledge-based biomarker discovery as a feature selection problem guided by prior information. These methods often require that prior information is encoded as a single score and the algorithms are optimized for biological knowledge of a specific type. However, in practice, domain knowledge from diverse resources can provide complementary information. But no current methods can integrate heterogeneous prior information for biomarker discovery. To address this problem, we developed the Know-GRRF (know-guided regularized random forest) method that enables dynamic incorporation of domain knowledge from multiple disciplines to guide feature selection.

Results

Know-GRRF embeds domain knowledge in a regularized random forest framework. It combines prior information from multiple domains in a linear model to derive a composite score, which, together with other tuning parameters, controls the regularization of the random forests model. Know-GRRF concurrently optimizes the weight given to each type of domain knowledge and other tuning parameters to minimize the AIC of out-of-bag predictions. The objective is to select a compact feature subset that has a high discriminative power and strong functional relevance to the biological phenotype.

Via rigorous simulations, we show that Know-GRRF guided by multiple-domain prior information outperforms feature selection methods guided by single-domain prior information or no prior information. We then applied Known-GRRF to a real-world study to identify prognostic biomarkers of prostate cancers. We evaluated the combination of cancer-related gene annotations, evolutionary conservation and pre-computed statistical scores as the prior knowledge to assemble a panel of biomarkers. We discovered a compact set of biomarkers with significant improvements on prediction accuracies.

Conclusions

Know-GRRF is a powerful novel method to incorporate knowledge from multiple domains for feature selection. It has a broad range of applications in biomarker discoveries. We implemented this method and released a KnowGRRF package in the R/CRAN archive.
Amazing symmetrical clustering in chloroplast genomes
Authors: Sadovsky Michael G. , Senashova Maria Yu , Malyshev Andrew V.
Published: March 2020

Background

Previously, a seven-cluster pattern claiming to be a universal one in bacterial genomes has been reported. Keeping in mind the most popular theory of chloroplast origin, we checked whether a similar pattern is observed in chloroplast genomes.

Results

Surprisingly, eight cluster structure has been found, for chloroplasts. The pattern observed for chloroplasts differs rather significantly, from bacterial one, and from that latter observed for cyanobacteria. The structure is provided by clustering of the fragments of equal length isolated within a genome so that each fragment is converted in triplet frequency dictionary with non-overlapping triplets with no gaps in frame tiling. The points in 63-dimensional space were clustered due to elastic map technique. The eight cluster found in chloroplasts comprises the fragments of a genome bearing tRNA genes and exhibiting excessively high GC-content, in comparison to the entire genome.

Conclusion

Chloroplasts exhibit very specific symmetry type in distribution of coding and non-coding fragments of a genome in the space of triplet frequencies: this is mirror symmetry. Cyanobacteria may have both mirror symmetry, and the rotational symmetry typical for other bacteria.
Robust pathway sampling in phenotype prediction. Application to triple negative breast cancer
Authors: Cernea Ana , Fernández-Martínez Juan Luis , deAndrés-Galiana Enrique J. , Fernández-Ovies Francisco Javier , Alvarez-Machancoses Oscar , Fernández-Muñiz Zulima , Saligan Leorey N. , Sonis Stephen T.
Published: March 2020

Background

Phenotype prediction problems are usually considered ill-posed, as the amount of samples is very limited with respect to the scrutinized genetic probes. This fact complicates the sampling of the defective genetic pathways due to the high number of possible discriminatory genetic networks involved. In this research, we outline three novel sampling algorithms utilized to identify, classify and characterize the defective pathways in phenotype prediction problems, such as the Fisher’s ratio sampler, the Holdout sampler and the Random sampler, and apply each one to the analysis of genetic pathways involved in tumor behavior and outcomes of triple negative breast cancers (TNBC). Altered biological pathways are identified using the most frequently sampled genes and are compared to those obtained via Bayesian Networks (BNs).

Results

Random, Fisher’s ratio and Holdout samplers were more accurate and robust than BNs, while providing comparable insights about disease genomics.

Conclusions

The three samplers tested are good alternatives to Bayesian Networks since they are less computationally demanding algorithms. Importantly, this analysis confirms the concept of “biological invariance” since the altered pathways should be independent of the sampling methodology and the classifier used for their inference. Nevertheless, still some modifications are needed in the Bayesian networks to be able to sample correctly the uncertainty space in phenotype prediction problems, since the probabilistic parameterization of the uncertainty space is not unique and the use of the optimum network might falsify the pathways analysis.
Applications of machine learning for simulations of red blood cells in microfluidic devices
Authors: Bachratý Hynek , Bachratá Katarína , Chovanec Michal , Jančigová Iveta , Smiešková Monika , Kovalčíková Kristína
Published: March 2020

Background

For optimization of microfluidic devices for the analysis of blood samples, it is useful to simulate blood cells as elastic objects in flow of blood plasma. In such numerical models, we primarily need to take into consideration the movement and behavior of the dominant component of the blood, the red blood cells. This can be done quite precisely in small channels and within a short timeframe. However, larger volumes or timescales require different approaches. Instead of simplifying the simulation, we use a neural network to predict the movement of the red blood cells.

Results

The neural network uses data from the numerical simulation for learning, however, the simulation needs only be run once. Alternatively, the data could come from video processing of a recording of a biological experiment. Afterwards, the network is able to predict the movement of the red blood cells because it is a system of bases that gives an approximate cell velocity at each point of the simulation channel as a linear combination of bases.In a simple box geometry, the neural network gives results comparable to predictions using fluid streamlines, however in a channel with obstacles forming slits, the neural network is about five times more accurate.The network can also be used as a discriminator between different situations. We observe about two-fold increase in mean relative error when a network trained on one geometry is used to predict trajectories in a modified geometry. Even larger increase was observed when it was used to predict trajectories of cells with different elastic properties.

Conclusions

While for uncomplicated box channels there is no advantage in using a system of bases instead of a simple prediction using fluid streamlines, in a more complicated geometry, the neural network is significantly more accurate. Another application of this system of bases is using it as a comparison tool for different modeled situations. This has a significant future potential when applied to processing data from videos of microfluidic flows.
Frailty assessment and risk prediction by GRACE score in older patients with acute myocardial infarction
Authors: Anand Atul , Cudmore Sarah , Robertson Shirley , Stephen Jacqueline , Haga Kristin , Weir Christopher J. , Murray Scott A. , Boyd Kirsty , Gunn Julian , Iqbal Javaid , MacLullich Alasdair , Shenkin Susan D. , Fox Keith A. A. , Mills Nicholas , Denvir Martin A.
Published: March 2020

Background

Risk prediction after myocardial infarction is often complex in older patients. The Global Registry of Acute Coronary Events (GRACE) model includes clinical parameters and age, but not frailty. We hypothesised that frailty would enhance the prognostic properties of GRACE.

Methods

We performed a prospective observational cohort study in two independent cardiology units: the Royal Infirmary of Edinburgh, UK (primary cohort) and the South Yorkshire Cardiothoracic Centre, Sheffield, UK (external validation). The study sample included 198 patients ≥65 years old hospitalised with type 1 myocardial infarction (primary cohort) and 96 patients ≥65 years old undergoing cardiac catheterisation for myocardial infarction (external validation). Frailty was assessed using the Clinical Frailty Scale (CFS). The GRACE 2.0 estimated risk of 12-month mortality, Charlson comorbidity index and Karnofsky disability scale were also determined for each patient.

Results

Forty (20%) patients were frail (CFS ≥5). These individuals had greater comorbidity, functional impairment and a higher risk of death at 12 months (49% vs. 9% in non-frail patients, p < 0.001). The hazard of 12-month all-cause mortality nearly doubled per point increase in CFS after adjustment for age, sex and comorbidity (Hazard Ratio [HR] 1.90, 95% CI 1.47–2.44, p < 0.001). The CFS had good discrimination for mortality by Receiver Operating Characteristic (ROC) curve analysis (Area Under the Curve [AUC] 0.81, 95% CI 0.72–0.89) and enhanced the GRACE estimate (AUC 0.86 vs. 0.80 without CFS, p = 0.04). At existing GRACE thresholds, the CFS resulted in a Net Reclassification Improvement (NRI) of 0.44 (95% CI 0.28–0.60, p < 0.001), largely through reductions in risk estimates amongst non-frail patients. Similar findings were observed in the external validation cohort (NRI 0.46, 95% CI 0.23–0.69, p < 0.001).

Conclusions

The GRACE score overestimated mortality risk after myocardial infarction in these cohorts of older patients. The CFS is a simple guided frailty tool that may enhance prediction in this setting. These findings merit evaluation in larger cohorts of unselected patients.

Trial registration

Clinicaltrials.gov; NCT02302014 (November 26th 2014, retrospectively registered).
Predictors of acute intracranial hemorrhage and recurrence of chronic subdural hematoma following burr hole drainage
Authors: Chen Fu Mei , Wang Ke , Xu Kang Li , Wang Li , Zhan Tian Xiang , Cheng Fei , Wang Hao , Chen Zuo-Bing , Gao Liang , Yang Xiao Feng
Published: March 2020

Background

To investigate predictors of postoperative acute intracranial hemorrhage (AIH) and recurrence of chronic subdural hematoma (CSDH) after burr hole drainage.

Methods

A multicenter retrospective study of patients who underwent burr hole drainage for CSDH between January 2013 and March 2019.

Results

A total of 448 CSDH patients were enrolled in the study. CSDH recurrence occurred in 60 patients, with a recurrence rate of 13.4%. The mean time interval between initial burr hole drainage and recurrence was 40.8 ± 28.3 days. Postoperative AIH developed in 23 patients, with an incidence of 5.1%. The mean time interval between initial burr hole drainage and postoperative AIH was 4.7 ± 2.9 days. Bilateral hematoma, hyperdense hematoma and anticoagulant drug use were independent predictors of recurrence in the multiple logistic regression analyses. Preoperative headache was an independent risk factor of postoperative AIH in the multiple logistic regression analyses, however, intraoperative irrigation reduced the incidence of postoperative AIH.

Conclusions

This study found that bilateral hematoma, hyperdense hematoma and anticoagulant drug use were independently associated with CSDH recurrence. Clinical presentation of headache was the strongest predictor of postoperative AIH, and intraoperative irrigation decreased the incidence of postoperative AIH.
Sustained HIV viral suppression among men who have sex with men in the Miami-Dade County Ryan White Program: the effect of demographic, psychosocial, provider and neighborhood factors
Authors: Sheehan Diana M. , Dawit Rahel , Gbadamosi Semiu O. , Fennie Kristopher P. , Li Tan , Gebrezgi Merhawi , Brock Petra , Ladner Robert A. , Trepka Mary Jo
Published: March 2020

Background

HIV viral suppression is associated with health benefits for people living with HIV and a decreased risk of HIV transmission to others. The objective was to identify demographic, psychosocial, provider and neighborhood factors associated with sustained viral suppression among gay, bisexual, and other men who have sex with men.

Methods

Data from adult men who have sex with men (MSM) enrolled in the Miami-Dade County Ryan White Program (RWP) before 2017 were used. Sustained viral suppression was defined as having an HIV viral load < 200 copies/ml in all viral load tests in 2017. Three-level (individual, medical case management site, and neighborhood) cross-classified mixed-effect models were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for sustained viral suppression.

Results

Of 3386 MSM, 90.8% were racial/ethnic minorities, and 84.4% achieved sustained viral suppression. The odds of achieving sustained viral suppression was lower for 18–24 and 25–34 year-old MSM compared with 35–49 year-old MSM, and for non-Latino Black MSM compared with White MSM. Those not enrolled in the Affordable Care Act, and those with current AIDS symptoms and a history of AIDS had lower odds of achieving sustained viral suppression. Psychosocial factors significantly associated with lower odds of sustained viral suppression included drug/alcohol use, mental health symptoms, homelessness, and transportation to appointment needs. Individuals with an HIV physician who serves a larger volume of RWP clients had greater odds of sustained viral suppression. Neighborhood factors were not associated with sustained viral suppression.

Conclusion

Despite access to treatment, age and racial disparities in sustained viral suppression exist among MSM living with HIV. Addressing substance use, mental health, and social services’ needs may improve the ability of MSM to sustain viral suppression long-term. Furthermore, physician characteristics may be associated with HIV outcomes and should be explored further.
Oral management of a patient with down syndrome and agammaglobulinemia: a case report
Authors: Kusumoto Yasuka , Imai Kohsuke , Ohyama Yoshio , Fukayama Haruhisa , Shinozuka Osamu
Published: March 2020

Background

Down syndrome is characterized by a variety of dysmorphic features and congenital malformations, such as congenital heart disease, gastrointestinal disease, and other conditions like leukemia and autoimmune disorders. Patients with Down syndrome are highly prone to respiratory tract infections, which might be fatal to them. However, there are only few available data on patients diagnosed with Down syndrome and agammaglobulinemia. In this report, we describe a case of successful prevention of post-dental treatment complications (e.g., pneumonia and other bacterial infections) in a patient with Down syndrome and agammaglobulinemia.

Case presentation

A 43-year-old man with Down syndrome, untreated agammaglobulinemia, and a history of recurrent pneumonia, was referred to our clinic for tooth mobility. To reduce the risk of post-operative infections, gammaglobulin treatment and prophylactic administration of antibiotics was scheduled before the dental procedure. Furthermore, the dental treatment, which included a filling and extractions, was conducted under general anesthesia and with the supervision of a hematologist. The dental procedures were successfully performed without any post-operative infection, and the patient is undergoing follow-up care.

Conclusions

The purpose of this case report was to recommend a close liaison between physicians and dentists who may encounter a similar case, and to emphasize the importance of improving oral health of immunodeficient patients to prevent infections caused by oral microbial flora.
Effect of Chinese eye exercises on change in visual acuity and eyeglasses wear among school-aged children in rural China: a propensity-score-matched cohort study
Authors: Wang Huan , Qian Yiwei , Congdon Nathan , Boswell Matthew , Rozelle Scott , Ma Xiaochen
Published: March 2020

Background

Daily “eye exercises,” massaging of periocular acupuncture pressure points, have been part of China’s national vision care policy in schools for some 50 years. However, the effect of eye exercises on myopia progression and eyeglasses wear has not been definitively investigated. This study evaluates the effectiveness of eye exercises on visual acuity and the propensity of rural children to wear eyeglasses.

Methods

Cohort study in 252 randomly-selected rural schools with baseline in September 2012 and follow up surveys 9 and 21 months later. Outcomes were assessed using propensity-score matching (PSM), multivariate linear regression and logistic regression to adjust for differences between children performing and not performing eye exercises.

Results

Among 19,934 children randomly selected for screening, 2374 myopic (spherical equivalent refractive error ≤ − 0.5 diopters in either eye) children (11.9%, mean age 10.5 [Standard Error 1.08] years, 48.5% boys) had VA in either eye ≤6/12 without eyeglasses correctable to > 6/12 with eyeglasses. Among these who completed the 21-month follow up, 1217 (58.2%) children reported practicing eye exercises on school days and 874 (41.8%) did not. After propensity-score matching, 1652 (79%) children were matched: 826 (50%) in the Eye Exercises group and 826 (50%) in the No Exercise group. Performing eye exercises was not associated with change in LogMAR uncorrected visual acuity and wear of eyeglasses, using either logistic regression or PSM at 9 or 21 months.

Conclusions

We found no evidence for an effect of eye exercises on change in vision or eyeglasses wear.

Trial registration

The original trial (Registration site: http://isrctn.org. Registration number: ISRCTN03252665) was retrospectively registered 25/09/2012.
Supporting social prescribing in primary care by linking people to local assets: a realist review
Authors: Tierney Stephanie , Wong Geoff , Roberts Nia , Boylan Anne-Marie , Park Sophie , Abrams Ruth , Reeve Joanne , Williams Veronika , Mahtani Kamal R.
Published: March 2020

Background

Social prescribing is a way of addressing the ‘non-medical’ needs (e.g. loneliness, debt, housing problems) that can affect people’s health and well-being. Connector schemes (e.g. delivered by care navigators or link workers) have become a key component to social prescribing’s delivery. Those in this role support patients by either (a) signposting them to relevant local assets (e.g. groups, organisations, charities, activities, events) or (b) taking time to assist them in identifying and prioritising their ‘non-medical’ needs and connecting them to relevant local assets. To understand how such connector schemes work, for whom, why and in what circumstances, we conducted a realist review.

Method

A search of electronic databases was supplemented with Google alerts and reference checking to locate grey literature. In addition, we sent a Freedom of Information request to all Clinical Commissioning Groups in England to identify any further evaluations of social prescribing connector schemes. Included studies were from the UK and focused on connector schemes for adult patients (18+ years) related to primary care.

Results

Our searches resulted in 118 included documents, from which data were extracted to produce context-mechanism-outcome configurations (CMOCs). These CMOCs underpinned our emerging programme theory that centred on the essential role of ‘buy-in’ and connections. This was refined further by turning to existing theories on (a) social capital and (b) patient activation.

Conclusion

Our realist review highlights how connector roles, especially link workers, represent a vehicle for accruing social capital (e.g. trust, sense of belonging, practical support). We propose that this then gives patients the confidence, motivation, connections, knowledge and skills to manage their own well-being, thereby reducing their reliance on GPs. We also emphasise within the programme theory situations that could result in unintended consequences (e.g. increased demand on GPs).
A novel c-Kit/phospho-prohibitin axis enhances ovarian cancer stemness and chemoresistance via Notch3—PBX1 and β-catenin—ABCG2 signaling
Authors: Fang Chia-Hsun , Lin Yi-Te , Liang Chi-Ming , Liang Shu-Mei
Published: March 2020

Background

The underlying mechanism involved in ovarian cancer stemness and chemoresistance remains largely unknown. Here, we explored whether the regulation of c-Kit and plasma membrane prohibitin (PHB) affects ovarian cancer stemness and chemotherapy resistance.

Methods

Mass spectrum analysis and an in vitro kinase assay were conducted to examine the phosphorylation of PHB at tyrosine 259 by c-Kit. The in vitro effects of c-Kit on membrane raft-PHB in ovarian cancer were determined using tissue microarray (TMA)-based immunofluorescence, western blotting, immunoprecipitation, colony and spheroid formation, cell migration and cell viability assays. In vivo tumor initiation and carboplatin treatment were conducted in nude mice.

Results

We found that c-Kit and PHB colocalized in the raft domain and were positively correlated in human ovarian serous carcinoma. c-Kit interacted with PHB and facilitated the phosphorylation of PHB at tyrosine 259 (phospho-PHBY259) in the membrane raft to enhance ovarian cancer cell motility. The generation of SKOV3GL-G4, a metastatic phenotype of SKOV3 green fluorescent protein and luciferase (GL) ovarian cancer cells, in xenograft murine ascites showed a correlation between metastatic potential and stem cell characteristics, as indicated by the expression of c-Kit, Notch3, Oct4, Nanog and SOX2. Further study revealed that after activation by c-Kit, raft-phospho-PHBY259 interacted with Notch3 to stabilize Notch3 and increase the downstream target PBX1. Downregulation of raft-phospho-PHBY259 increased the protein degradation of Notch3 through a lysosomal pathway and inhibited the β-catenin—ABCG2 signaling pathway. Moreover, raft-phospho-PHBY259 played an important role in ovarian cancer stemness and tumorigenicity as well as resistance to platinum drug treatment in vitro and in vivo.

Conclusions

These findings thus reveal a hitherto unreported interrelationship between c-Kit and PHB as well as the effects of raft-phospho-PHBY259 on ovarian cancer stemness and tumorigenicity mediated by the Notch3 and β-catenin signaling pathways. Targeting the c-Kit/raft-phospho-PHBY259 axis may provide a new therapeutic strategy for treating patients with ovarian cancer.
Sema4A is implicated in the acceleration of Th17 cell-mediated neuroinflammation in the effector phase
Authors: Koda Toru , Namba Akiko , Kinoshita Makoto , Nakatsuji Yuji , Sugimoto Tomoyuki , Sakakibara Kaori , Tada Satoru , Shimizu Mikito , Yamashita Kazuya , Takata Kazushiro , Ishikura Teruyuki , Murata Syo , Beppu Shohei , Kumanogoh Atsushi , Mochizuki Hideki , Okuno Tatsusada
Published: March 2020

Background

Sema4A is a regulator of helper T cell (Th) activation and differentiation in the priming phase, which plays an important role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS). However, the role of Sema4A in the effector phase remains elusive. We aimed to investigate the role of Sema4A at the effector phase in adoptively transferred EAE model. Clinical features and cytokine profiles of MS patients with high Sema4A levels were also examined in detail to clarify the correlation between Sema4A levels and disease activity of patients with MS.

Methods

We adoptively transferred encephalitogenic Th1 or Th17 cells to wild type (WT) or Sema4A-deficient (Sema4A KO) mice and assessed severity of symptoms and cellular infiltration within the central nervous system (CNS). In addition, we analyzed clinical and radiological features (n = 201), levels of serum IFN-γ and IL-17A (n = 86), complete remission ratio by IFN-β (n = 38) in all of relapsing-remitting multiple sclerosis (RRMS) patients enrolled in this study.

Results

Sema4A KO recipient mice receiving Th17-skewed WT myelin oligodendrocyte glycoprotein (MOG)-specific encephalitogenic T cells showed a significant reduction in the clinical score compared to the WT recipient mice. However, Sema4A KO recipient mice showed similar disease activity to the WT recipient mice when transferred with Th1-skewed encephalitogenic T cells. Bone marrow chimeric study indicated that Sema4A expressed on hematopoietic cells, but not the CNS resident cells, are responsible for augmenting Th17-mediated neuroinflammation. Additionally, in contrast to comparable IFN-γ levels, IL-17A is significantly higher in RRMS patients with high Sema4A level than those with low Sema4A patients with high Sema4A levels showed earlier disease onset, more severe disease activity and IFN-β unresponsiveness than those with low Sema4A levels.

Conclusions

Sema4A is involved not only in the Th cell priming but also in the acceleration of Th17 cell-mediated neuroinflammation in the effector phase, which could contribute to the higher disease activity observed in RRMS patients with high serum Sema4A levels.
A probable role of copper in the comorbidity in Wilson’s and Creutzfeldt-Jakob’s Diseases: a case report
Authors: Koutsouraki Effrosyni , Michmizos Dimitrios , Patsi Olga , Tzartos John , Spilioti Martha , Arnaoutoglou Marianthi , Tsolaki Magda
Published: March 2020

Background

To the best of our knowledgedd, there is currently no case in the literature reporting the comorbidity of Wilson’s and Creutzfeldt-Jakob disease (CJD), linked through copper.

Case presentation

A 44-year-old male with a history of inherited Wilson’s disease (hepatolenticular degeneration), which manifested as mild liver injury and psychiatric symptoms, was admitted to our department due to speech and cognitive disturbances. Upon his admission, he had motor aphasia as well as psychomotor retardation with an otherwise normal neurological examination. Laboratory tests, including liver enzymes, copper and serum ammonia were all within normal range. The brain MRI showed increased T2 signal in the caudate nuclei, attributed to copper deposition in the context of Wilson’s disease. In the electroencephalogram, periodic sharp discharges were eminent, initially unilateral and then generalized. The positive 14–3-3 protein in the cerebrospinal fluid (CSF) and the new brain MRI, that demonstrated elevated DWI signal not only in the basal ganglia but also in parts of the cerebral cortex (cortical ribbon sign), all supportive of a possible CJD diagnosis. The detection of PrPSc in the patient’s CSF, using the RT-QuIC method, which has a 99.4–100% specificity for CJD, made the diagnosis of CJD highly probable.

Conclusion

This is the first report of Wilson’s and Creutzfeldt-Jakob diseases co-morbidity in the literature, which could evoke a possible role of copper in the pathogenesis of CJD.
Runners' metabolomic changes following marathon
Authors: Shi Rengfei , Zhang Jin , Fang Biqing , Tian Xiangyang , Feng Yu , Cheng Zepeng , Fu Zhongyu , Zhang Jingjing , Wu Jiaxi
Published: March 2020

Introduction

Marathon, as a long-distance aerobic exercise, has become a fashionable or popular sport. However, little is known about the holistic metabolic changes occurring within the serum metabolome of athletes after the completion of a marathon.

Objectives

The goal of current study was to have an in-depth understanding of the impact of marathon on human metabolomics as well as the relationships among a variety of metabolites.

Methods

The 20 studied subjects were all adult males who participated in a marathon. The serum samples of these participants were collected before and after the marathon and the biochemical metabolites in the serum were identified by an untargeted two-dimensional gas chromatography time-of-flight mass spectrometry.

Results

All participants completed the marathon within 3 h. Compared to those before exercise, serum urea and creatine kinase, as well as cortisol, elevated significantly (p < 0.05), whereas testosterone decreased significantly (p < 0.01). Metabolomic analysis showed that, compared to those before the competition, metabolites pyruvic acid, glyceric acid, malic acid, cis-aconitic acid, galacturonic acid, methyl fumaric acid, maltotriose, and others increased significantly after the competition (p < 0.05), but glucosamine and O-succinyl-L-homoserine decreased significantly (p < 0.05). Amino acid indexes, such as alanine, L-tyrosine and phenylalanine, increased significantly after exercise compared with those before exercise (p < 0.05), whereas serine, valine and asparagine decreased significantly (p < 0.05). Lipid metabolism indexes, glycerol, glyceric acid, octanoic acid, and quinic acid increased significantly (p < 0.05). Theophylline, xanthine and other indicators of caffeine metabolism increased significantly (p < 0.05). Furthermore, marathon performance, fat percentage, VO2max, and hemoglobin were correlated with the serum metabonomic indicators, so were serum testosterone and cortisol.

Conclusion

These results illustrate that the metabolism of glucose and lipid of the athletes was enhanced following the marathon match. In addition, the metabolism of glucosamine was decreased and the metabolism of caffeine was increased. Our data provide new insights for marathon performance and nutritional status.
Comparison of Instrumental Activities of Daily Living assessment by face-to-face or telephone interviews: a randomized, crossover study
Authors: Dauphinot Virginie , Boublay Nawèle , Moutet Claire , Achi Sarah , Bathsavanis Anthony , Krolak-Salmon Pierre
Published: March 2020

Background

The functional autonomy assessment is essential to manage patients with a neurodegenerative disease, but its evaluation is not always possible during a consultation. To optimize ambulatory autonomy assessment, we compared the Lawton Instrumental Activities of Daily Living (IADL) questionnaire collected by telephone and face-to-face interviews.

Methods

A randomized, crossover study was carried out among patients attending a memory clinic (MC). The IADL questionnaire was collected for patients during telephone and face-to-face interviews between nurses and patients’ caregivers. The agreement between the two methods was measured using the proportion of participants giving the same response, Cohen’s kappa, intraclass correlation (ICC) coefficient, and Bland and Altman method. The associations between patients’ characteristics, events occurring between the two assessments, and agreement were assessed.

Results

Among the 292 patients (means ± SD age 81.5 ± 7, MMSE 19.6 ± 6, 39.7% with major neurocognitive disorders) analyzed, the proportion of agreement between the two modes was 89.4% for the total IADL score. Weighted kappa coefficient was 0.66 and ICC score was 0.91 for total IADL score. The mean difference between the IADL score by telephone or face-to-face was 0.32. Overall, 96.9% of measures lay within the 95% limits of agreement. The occurrence of fall was less likely associated with the probability to lie within the 95% limits of agreement (OR = 0.07 [0.02–0.27]).

Conclusion

The administration of IADL by telephone with the caregiver appears to be an acceptable method of assessment for MC patients compared to face-to-face interview. The events such as falls which could occur in a time close to the evaluation should be reported.

Study registration

ClinicalTrials.gov, NCT02654574. Retrospectively registered: 13 January 2016
Microvesicles derived from human Wharton’s jelly mesenchymal stem cells enhance autophagy and ameliorate acute lung injury via delivery of miR-100
Authors: Chen Wen-xia , Zhou Jun , Zhou Sha-sha , Zhang Yu-dan , Ji Tong-yu , Zhang Xiao-li , Wang Shu-min , Du Tao , Ding De-gang
Published: March 2020

Objectives

Microvesicles (MVs) derived from human Wharton’s jelly mesenchymal stem cells (MSC-MVs) were demonstrated to ameliorate acute lung injury (ALI). We have previously found that MSC-MV-transferred hepatocyte growth factor was partly involved in their therapeutic effects. Since MSC-MVs also contained a substantial quantity of miR-100, which plays an important role in lung cancer and injury, we speculated that miR-100 might similarly account for a part of the therapeutic effects of MSC-MVs.

Methods

MSCs were transfected with miR-100 inhibitor to downregulate miR-100 in MSC-MVs. A rat model of ALI and cell injury in rat type II alveolar epithelial cell line (L2) was induced by bleomycin (BLM). A co-culture model of alveolar epithelial cells and MSC-MVs was utilized to examine the therapeutic role of MSC-MVs and mechanism.

Results

MSC-MV treatment attenuated BLM-induced apoptosis and inflammation in BLM-treated L2 cells and ameliorated BLM-induced lung apoptosis, inflammation, and fibrosis in BLM-induced ALI rats. The beneficial effect of MSC-MVs was partly eliminated when miR-100 was knocked down in MSCs. Moreover, MSC-MV-transferred miR-100 mediated the therapeutic effect of MSC-MVs in ALI through enhancing autophagy by targeting mTOR.

Conclusion

MSC-MVs enhance autophagy and ameliorate ALI partially via delivery of miR-100.
Bilateral Aldosterone Suppression in Patients With Right Unilateral Primary Aldosteronism and Review of the Literature
Authors: Tan Sarah Ying Tse , Ng Keng Sin , Tan Colin , Chuah Matthew , Zhang Meifen , Puar Troy H
Published: March 2020

Introduction

Adrenal vein sampling (AVS) identifies unilateral primary aldosteronism but may occasionally show paradoxically low aldosterone–cortisol ratios bilaterally. Postulated reasons include venous anomalies, fluctuating aldosterone secretion, or superselective cannulation. We report our findings in patients who underwent repeat AVS and reviewed the current literature.

Methods

We performed a retrospective observational study of patients undergoing AVS in an experienced high-volume tertiary center over a 5-year period.

Results

From 2015 to 2019, 61 patients underwent sequential cosyntropin-stimulated AVS and all had bilateral successful cannulation (100%). Four of 61 (6.6%) patients had bilaterally low aldosterone–cortisol ratios. Three patients underwent repeat AVS, with all 3 cases demonstrating right-sided lateralization and cure of disease postadrenalectomy. Right-sided disease was also more common in other reports. This may be due to inadvertent superselective cannulation of the short right adrenal vein, resulting in sampling of the adjacent normal gland. Cortisol results cannot detect this problem. In 1 patient, computed tomography venography excluded any accessory right adrenal veins. In another patient, repeat bilateral simultaneous unstimulated AVS was done, and measurements of metanephrines aided in accurately identifying right-sided lateralization.

Conclusion

In addition to technical difficulties in cannulating the right adrenal vein, we also have to avoid performing superselective cannulation inadvertently. In cases of inconclusive AVS, repeat sampling may identify patients with potentially curable unilateral primary aldosteronism. The role of corticotropin stimulation and metanephrines measurements during repeat AVS requires further study.
Glycogen Utilization during Running: Intensity, Sex, and Muscle-Specific Responses
Authors: IMPEY SAMUEL G. , JEVONS EMILY , MEES GEORGE , COCKS MATT , STRAUSS JULIETTE , CHESTER NEIL , LAURIE IEVA , TARGET DARREN , HODGSON ADRIAN , SHEPHERD SAM O. , MORTON JAMES P.
Published: March 2020

Purpose

This study aimed to quantify net glycogen utilization in the vastus lateralis (VL) and gastrocnemius (G) of male (n = 11) and female (n = 10) recreationally active runners during three outdoor training sessions.

Methods

After 2-d standardization of carbohydrate intakes (6 g·kg−1 body mass per day), glycogen was assessed before and after 1) a 10-mile road run (10-mile) at lactate threshold, 2) 8 × 800-m track intervals (8 × 800 m) at velocity at V˙O2max, and 3) 3 × 10-min track intervals (3 × 10 min) at lactate turnpoint.

Results

Resting glycogen concentration was lower in the G of female compared with males (P < 0.001) runners, although no sex differences were apparent in the VL (P = 0.40). Within the G and VL of male runners, net glycogen utilization differed between training sessions where 10 miles was greater than both track sessions (all comparisons, P < 0.05). In contrast, net glycogen utilization in female runners was not different between training sessions in either muscle (all comparisons, P > 0.05). Net glycogen utilization was greater in male than in female runners in both VL (P = 0.02) and G (P = 0.07) during the 10-mile road run. With the exception of male runners during the 3 × 10-min protocol (P = 0.28), greater absolute glycogen utilization was observed in the G versus the VL muscle in both male and female runners and during all training protocols (all comparisons, P < 0.05).

Conclusion

Data demonstrate that 1) prolonged steady-state running necessitates a greater glycogen requirement than shorter but higher-intensity track running sessions, 2) female participants display evidence of reduced resting muscle glycogen concentration and net muscle glycogen utilization when compared with male participants, and 3) net glycogen utilization is higher in the G muscle compared with the VL.
Sports Drink Intake Pattern Affects Exogenous Carbohydrate Oxidation during Running
Authors: MEARS STEPHEN A. , BOXER BENJAMIN , SHELDON DAVID , WARDLEY HANNAH , TARNOWSKI CAROLINE A. , JAMES LEWIS J. , HULSTON CARL J.
Published: March 2020

Purpose

This study aimed to determine whether the pattern of carbohydrate sports drink ingestion during prolonged submaximal running affects exogenous carbohydrate oxidation rates and gastrointestinal (GI) comfort.

Methods

Twelve well-trained male runners (27 ± 7 yr; 67.9 ± 6.7 kg; V˙O2peak, 68 ± 7 mL·kg−1·min−1) completed two exercise trials of 100 min steady-state running at 70%V˙O2peak. In each of the trials, 1 L of a 10% dextrose solution, enriched with [U-13C] glucose, was consumed as either 200 mL every 20 min (CHO-20) or 50 mL every 5 min (CHO-5). Expired breath and venous blood samples were collected at rest and every 20 min during exercise. Subjective scales of GI comfort were recorded at regular intervals.

Results

Average exogenous carbohydrate oxidation rates were 23% higher during exercise in CHO-20 (0.38 ± 0.11 vs 0.31 ± 0.11 g·min−1; P = 0.017). Peak exogenous carbohydrate oxidation was also higher in CHO-20 (0.68 ± 0.14 g·min−1 vs 0.61 ± 0.14 g·min−1; P = 0.004). During exercise, total carbohydrate oxidation (CHO-20, 2.15 ± 0.47; CHO-5, 2.23 ± 0.45 g·min−1, P = 0.412) and endogenous carbohydrate oxidation (CHO-20, 1.78 ± 0.45; CHO-5, 1.92 ± 0.40 g·min−1; P = 0.148) were not different between trials. Average serum glucose (P = 0.952) and insulin (P = 0.373) concentrations were not different between trials. There were no differences in reported symptoms of GI comfort and stomach bloatedness (P > 0.05), with only 3% of reported scores classed as severe (≥5 out of 10).

Conclusion

Ingestion of a larger volume of carbohydrate solution at less frequent intervals during prolonged submaximal running increased exogenous carbohydrate oxidation rates. Neither drinking pattern resulted in increased markers of GI discomfort to a severe level.
Plasma calprotectin as a biomarker of mortality at antiretroviral treatment initiation in advanced HIV – pilot study
Authors: Kamau Faith W. , Gwela Agnes , Nyerere Andrew K. , Riitho Victor , Njunge James M. , Ngari Moses M. , Prendergast Andrew J. , Berkley James A.
Published: March 2020

Background: In advanced HIV, significant mortality occurs soon after starting antiretroviral treatment (ART) in low- and middle-incomes countries. Calprotectin is a biomarker of innate response to infection and inflammatory conditions. We examined the association between plasma calprotectin at initiation of ART and mortality among individuals with advanced HIV.

Methods: We conducted a pilot case-cohort study among HIV infected adults and children over 5 years old with CD4+ <100/mm3 at ART initiation at two Kenyan sites. Participants received three factorial randomised interventions in addition to ART within the REALITY trial (ISRCTN43622374). Calprotectin was measured by ELISA in archived plasma of those who died within 24 weeks (cases) and randomly selected participants who survived for 48 weeks (non-cases) for whom samples were available. Factors associated with baseline plasma calprotectin were investigated using linear regression. To test association with mortality, Cox proportional hazards models with inverse sampling probability weights and adjusted for age, sex, site, BMI, viral load, randomised treatments, and clustered by CD4 count were fitted.

Results: Baseline median (IQR) plasma calprotectin was 6.82 (2.65–12.5) µg/ml in cases (n=39) and 5.01 (1.92–11.5) µg/ml in non-cases (n=58). Baseline calprotectin was associated with age, neutrophil count and the presence of cough, but not other measured indicators of infection. In adjusted multivariable models, baseline calprotectin was associated with subsequent mortality: HR 1.64 (95% CI 1.11 - 2.42) and HR 2.77 (95% CI 1.58 - 4.88) for deaths during the first twenty-four and four weeks respectively. Calprotectin levels fell between baseline and 4 weeks among both cases and non-cases irrespective of randomised interventions.

Conclusion: Among individuals with advanced HIV starting ART in Kenya, plasma calprotectin may have potential as a biomarker of early mortality. Validation in larger studies, comparison with other biomarkers and investigation of the sources of infection and inflammation are warranted.
eHealth systems for the optimised care of patients with type 2 diabetes
Authors: Klösch Michael , Klösch Christoph , Kundt Firuzan Sari , van der Zee-Neuen Antje , Dieplinger Anna Maria
Published: March 2020

Background:

Type 2 diabetes mellitus is one of the most common diseases worldwide. The demands on health services are rising as more people are diagnosed with the condition. In order to meet this demand, eHealth systems are increasingly being integrated into nursing care.

Methods:

Between November 2018 and February 2019, a literature search was carried out in the databases PubMed and CINAHL.

Results:

Twenty articles were found on nurses' use of eHealth systems, the majority with patients with diabetes. From this research, it would seem that eHealth systems have had a proven positive influence on patients' state of health and understanding of therapy. Subjectively perceived communication with the nursing staff also improved. Problems can arise in the implementation phase.

Conclusion:

In the future, increasingly, nurses will have to integrate eHealth systems into the treatment of patients with type 2 diabetes. It is important that nurses understand such systems in order to guarantee a sustainable and successful implementation.
Introducing an oral care assessment tool with advanced cleaning products into a high-risk clinical setting
Authors: Chick Angela , Wynne Ahlam
Published: March 2020

Poor oral hygiene is an important risk factor for the development of non-ventilator hospital-associated pneumonia (NV-HAP), which imposes a significant burden on the NHS. This study aimed to establish whether the use of a 24-hour oral care kit and an oral care assessment tool can meet the needs of patients on an acute stroke unit. In comparison with the same period the preceding year, the introduction of the oral care kit and assessment tool improved compliance with oral care by more than 4 times; the overall costs of antibiotics to treat NV-HAP patients fell by 79%, with the number of doses falling by 70%, and the mortality rate decreased from 27% to 20%. According to a survey of multidisciplinary team (MDT) members keeping oral care tools available at the point of use saved time, and the oral health of patients on the unit improved after the introduction of the oral care kit and assessment tool. Almost all MDT members would recommend the use of the kit over previous interventions.
Using public health law to contain the spread of COVID-19
Authors: Griffith Richard
Published: March 2020

Richard Griffith, Senior Lecturer in Health Law at Swansea University, considers what powers are available to ministers, health and local authorities to minimise the spread of the novel coronavirus and the disease it causes
A comparison of inpatients with leg ulceration using published randomised controlled trials
Authors: Lian Yaping , Stather Philip , Gohel Manj
Published: March 2020

Background:

Leg ulcers are a significant burden and reduce patients' quality of life. In recent years, a plethora of information has been issued regarding leg ulcer management and ‘the demographics of patients affected in the community. However, little is known about the leg ulcer population and how these patients should be managed in acute hospitals.

Aim:

To compare the demographic data of inpatients with leg ulcers referred to the tissue viability service in a large teaching hospital with data on leg ulcer populations in acute and community settings.

Methods:

Inpatient demographic data were retrospectively obtained from electronic patient records. A literature search identified studies regarding leg ulcer populations in acute and community settings.

Results:

The patient population in acute settings is around 10 years older than that in community settings, with much greater levels of comorbidity and higher mortality rates.

Conclusion:

An improved understanding of inpatients with leg ulcers would allow investigations and interventions to be targeted better, enabling evidence-based, patient-centred referral and care pathways. Further research is required to understand the aetiology and outcomes of leg ulcers for the inpatient population.
The lived experience of patients from an ethnic group in Indonesia undergoing diabetic foot ulcer treatment
Authors: Suza Dewi Elizadiani , Eltrikanawati Tengku , Tarigan Rosina , Setiawan  , Gunawan Joko
Published: March 2020

Background:

A foot ulcer is a severe complications of diabetes, and patients' cultural backgrounds can greatly influence how they manage this condition.

Aim:

To explore the experience of people of the Batak Karo ethnic group in Indonesia in diabetic foot ulcer treatment.

Methods:

This was a phenomenological study where a purposeful sample of 10 people with diabetic foot ulcers participated in in-depth interviews. Data analysis was thematic using Van Manen's hermeneutic approach.

Results:

Five themes emerged from the study data: beliefs about health disorders; physical, psychological, social and spiritual changes; traditional treatments; cultural beliefs; and seeking health services.

Discussion:

People in the Batak Karo ethnic group strongly believe in supernatural powers and magic, and take part in a variety of traditional ceremonies to treat diabetic foot ulcers. They also use traditional treatments, including herbs. Nurses treating different ethnic groups, such as the Batak Karo people, should be culturally aware and competent to provide adequate care for them.
An international consensus on device-related pressure ulcers: SECURE prevention
Authors: Gefen Amit , Alves Paulo , Ciprandi Guido , Coyer Fiona , Milne Catherine , Ousey Karen , Ohura Norihiko , Waters Nicola , Worsley Peter , Black Joyce , Barakat-Johnson Michelle , Beeckman Dimitri , Fletcher Jacqui , Kirkland-Kyhn Holly , Lahmann Nils A. , Moore Zena , Payan Yohan , Schlüer Anna-Barbara
Published: March 2020

Catherine Milne and colleagues present the findings of their review, ccna2@juno.com