bluuebunny/crossref_metadata_2025 huggingface dataset:
Looking back to look forward: a review of human resources for health governance in South Africa from 1994 to 2018
Authors: Van Ryneveld Manya , Schneider Helen , Lehmann Uta
Published: November 2020

While South Africa has had a fairly consistent record of producing national-level strategic plans for human resources for health in the past 25 years, the country continues to face major problems of affordability, availability, distribution and management of its health workforce. There are several factors contributing to the state of health human resources in the country, but problems with governance stand out as one area requiring further research, analysis and critique. This paper presents a retrospective analysis of the historical patterns in national health human resources governance in South Africa, based on a desktop policy review spanning 25 years after democracy. The authors took a multi-pronged, iterative approach, reviewing policy documents alongside grey and published literature. This led to a timeline showing key legislation, relevant health system and human resource policies, interventions, reviews and evaluations from 1994 to 2018. The review identified three distinct periods that help to characterise the terrain of human resources for health governance over the concerned 25 years. Firstly, a foundational period, in which much of the constitutional and legislative groundwork was laid. Secondly, the HIV epidemic period, which presented a major disruption to the development of system wide governance interventions and improvements. Thirdly, the launch of National Health Insurance discussions and policy processes, which signalled a gradual return to a comprehensive systems focus in line with the founding principles of the first period. Using this periodisation, as well as a conceptual framework of health human resources governance functions based on international literature, the authors argue that South Africa has experienced both progress and challenges in human resources for health governance. This has affected the successful implementation of its policy and strategic planning over the past 25 years. Good governance for human resources for health requires capable stewardship, underpinned by an appropriate mix of technical and administrative skills and explicit political support. The review findings suggest that strengthening human resources for health governance roles, including fostering purposeful stewardship by the National Department of Health, may be key to shifting the terrain in the availability and performance of South Africa’s health workforce going forwards.
Advancing the global physical activity agenda: recommendations for future research by the 2020 WHO physical activity and sedentary behavior guidelines development group
Authors: DiPietro Loretta , Al-Ansari Salih Saad , Biddle Stuart J. H. , Borodulin Katja , Bull Fiona C. , Buman Matthew P. , Cardon Greet , Carty Catherine , Chaput Jean-Philippe , Chastin Sebastien , Chou Roger , Dempsey Paddy C. , Ekelund Ulf , Firth Joseph , Friedenreich Christine M. , Garcia Leandro , Gichu Muthoni , Jago Russell , Katzmarzyk Peter T. , Lambert Estelle , Leitzmann Michael , Milton Karen , Ortega Francisco B. , Ranasinghe Chathuranga , Stamatakis Emmanuel , Tiedemann Anne , Troiano Richard P. , van der Ploeg Hidde P. , Willumsen Juana F.
Published: November 2020

Background

In July, 2019, the World Health Organization (WHO) commenced work to update the 2010 Global Recommendations on Physical Activity for Health and established a Guideline Development Group (GDG) comprising expert public health scientists and practitioners to inform the drafting of the 2020 Guidelines on Physical Activity and Sedentary Behavior. The overall task of the GDG was to review the scientific evidence and provide expert advice to the WHO on the amount of physical activity and sedentary behavior associated with optimal health in children and adolescents, adults, older adults (> 64 years), and also specifically in pregnant and postpartum women and people living with chronic conditions or disabilities.

Methods

The GDG reviewed the available evidence specific to each sub-population using systematic protocols and in doing so, identified a number of gaps in the existing literature. These proposed research gaps were discussed and verified by expert consensus among the entire GDG.

Results

Evidence gaps across population sub-groups included a lack of information on: 1) the precise shape of the dose-response curve between physical activity and/or sedentary behavior and several of the health outcomes studied; 2) the health benefits of light-intensity physical activity and of breaking up sedentary time with light-intensity activity; 3) differences in the health effects of different types and domains of physical activity (leisure-time; occupational; transportation; household; education) and of sedentary behavior (occupational; screen time; television viewing); and 4) the joint association between physical activity and sedentary time with health outcomes across the life course. In addition, we acknowledge the need to conduct more population-based studies in low- and middle-income countries and in people living with disabilities and/or chronic disease, and to identify how various sociodemographic factors (age, sex, race/ethnicity, socioeconomic status) modify the health effects of physical activity, in order to address global health disparities.

Conclusions

Although the 2020 WHO Guidelines for Physical Activity and Sedentary Behavior were informed by the most up-to-date research on the health effects of physical activity and sedentary time, there is still substantial work to be done in advancing the global physical activity agenda.
The effect of a school-based intervention on physical activity, cardiorespiratory fitness and muscle strength: the School in Motion cluster randomized trial
Authors: Kolle Elin , Solberg Runar Barstad , Säfvenbom Reidar , Dyrstad Sindre M. , Berntsen Sveinung , Resaland Geir K. , Ekelund Ulf , Anderssen Sigmund A. , Steene-Johannessen Jostein , Grydeland May
Published: November 2020

Background

Physical activity (PA) declines throughout adolescence, therefore PA promotion during this period is important. We analyzed the effect of two school-based PA interventions on daily PA levels, cardiorespiratory fitness (CRF) and muscle strength among adolescents.

Methods

For the nine-month School in Motion intervention study (ScIM), we cluster-randomized 30 Norwegian secondary schools (N = 2084, mean age [SD] = 14 [0.3] years) to one of three study arms. The physically active learning (PAL) intervention included 30 min physically active learning, 30 min PA and a 60 min physical education (PE) lesson per week. The Don’t worry-Be happy (DWBH) intervention included a 60 min PA lesson and a 60 min PE lesson per week, both tailored to promote friendships and wellbeing. Both intervention arms were designed to engage the adolescents in 120 min of PA per week in addition to recess and mandatory PE lessons. The control group continued as per usual, including the standard amount of mandatory PE. PA (main outcome) was assessed by accelerometers, CRF and muscle strength (secondary outcomes) were assessed by an intermittent running test and selected tests from the Eurofit test battery.

Results

Daily PA and time spent in moderate- to vigorous-intensity PA (MVPA) decreased in all groups throughout the intervention. The mean difference in PA level and MVPA for participants in the PAL-intervention arm was 34.7 cpm (95% CI: 4.1, 65.3) and 4.7 min/day (95% CI: 0.6, 8.8) higher, respectively, compared to the control arm. There were no significant intervention effects on daily PA level, MVPA or time spent sedentary for adolescents in the DWBH-intervention arm. Adolescents in the PAL-intervention arm increased distance covered in the running test compared to controls (19.8 m, 95% CI: 10.4, 29.1), whilst a negative intervention effect was observed among adolescents in the DWBH-intervention arm (− 11.6 m, 95% CI: − 22.0, − 1.1).

Conclusion

The PAL-intervention resulted in a significantly smaller decrease in daily PA level, time spent in MVPA, and increased CRF compared to controls. Our results indicate that a teacher-led intervention, including three unique intervention components, is effective in curbing the decline in PA observed across our cohort and improving CRF.

Trial registration

ClinicalTrials.gov ID nr: NCT03817047. Registered 01/25/2019 ‘retrospectively registered’.
Functional characteristics of Th1, Th17, and ex-Th17 cells in EAE revealed by intravital two-photon microscopy
Authors: Loos Julia , Schmaul Samantha , Noll Theresa Marie , Paterka Magdalena , Schillner Miriam , Löffel Julian T. , Zipp Frauke , Bittner Stefan
Published: November 2020

Background

T helper (Th) 17 cells are a highly plastic subset of T cells, which in the context of neuroinflammation, are able to acquire pathogenic features originally attributed to Th1 cells (resulting in so called ex-Th17 cells). Thus, a strict separation between the two T cell subsets in the context of experimental autoimmune encephalomyelitis (EAE) is difficult. High variability in culture and EAE induction protocols contributed to previous conflicting results concerning the differential contribution of Th1 and Th17 cells in EAE. Here, we systematically evaluate the role of different T cell differentiation and transfer protocols for EAE disease development and investigate the functional dynamics of encephalitogenic T cells directly within the inflamed central nervous system (CNS) tissue.

Methods

We compiled the currently used EAE induction protocols reported in literature and investigated the influence of the different Th1 and Th17 differentiation protocols as well as EAE induction protocols on the EAE disease course. Moreover, we assessed the cytokine profile and functional dynamics of both encephalitogenic Th1 and Th17 cells in the inflamed CNS using flow cytometry and intravital two-photon laser scanning microscopy. Lastly, we used astrocyte culture and adoptive transfer EAE to evaluate the impact of Th1 and Th17 cells on astrocyte adhesion molecule expression in vitro and in vivo.

Results

We show that EAE courses are highly dependent on in vitro differentiation and transfer protocols. Moreover, using genetically encoded reporter mice (B6.IL17A-EGFP.acRFP x 2d2/2d2.RFP), we show that the motility of interferon (IFN)γ-producing ex-Th17 cells more closely resembles Th1 cells than Th17 cells in transfer EAE. Mechanistically, IFNγ-producing Th1 cells selectively induce the expression of cellular adhesion molecules I-CAM1 while Th1 as well as ex-Th17 induce V-CAM1 on astrocytes.

Conclusions

The behavior of ex-Th17 cells in EAE lesions in vivo resembles Th1 rather than Th17 cells, underlining that their change in cytokine production is associated with functional phenotype alterations of these cells.
Analysis of the efficacy of HIV protease inhibitors against SARS-CoV-2′s main protease
Authors: Mahdi Mohamed , Mótyán János András , Szojka Zsófia Ilona , Golda Mária , Miczi Márió , Tőzsér József
Published: November 2020

Background

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in millions of infections worldwide. While the search for an effective antiviral is still ongoing, experimental therapies based on repurposing of available antivirals is being attempted, of which HIV protease inhibitors (PIs) have gained considerable interest. Inhibition profiling of the PIs directly against the viral protease has never been attempted in vitro, and while few studies reported an efficacy of lopinavir and ritonavir in SARS-CoV-2 context, the mechanism of action of the drugs remains to be validated.

Methods

We carried out an in-depth analysis of the efficacy of HIV PIs against the main protease of SARS-CoV-2 (Mpro) in cell culture and in vitro enzymatic assays, using a methodology that enabled us to focus solely on any potential inhibitory effects of the inhibitors against the viral protease. For cell culture experiments a dark-to-bright GFP reporter substrate system was designed.

Results

Lopinavir, ritonavir, darunavir, saquinavir, and atazanavir were able to inhibit the viral protease in cell culture, albeit in concentrations much higher than their achievable plasma levels, given their current drug formulations. While inhibition by lopinavir was attributed to its cytotoxicity, ritonavir was the most effective of the panel, with IC50 of 13.7 µM. None of the inhibitors showed significant inhibition of SARS-CoV-2 Mpro in our in vitro enzymatic assays up to 100 µM concentration.

Conclusion

Targeting of SARS-CoV-2 Mpro by some of the HIV PIs might be of limited clinical potential, given the high concentration of the drugs required to achieve significant inhibition. Therefore, given their weak inhibition of the viral protease, any potential beneficial effect of the PIs in COVID-19 context might perhaps be attributed to acting on other molecular target(s), rather than SARS-CoV-2 Mpro.
Elevated l-threonine is a biomarker for Lassa fever and Ebola
Authors: Gale Trevor V. , Schieffelin John S. , Branco Luis M. , Garry Robert F. , Grant Donald S.
Published: November 2020

Background

Lassa fever and Ebola are characterized by non-specific initial presentations that can progress to severe multisystem illnesses with high fatality rates. Samples from additional subjects are examined to extend and corroborate biomarkers with prognostic value for these diseases.

Methods

Liquid Chromatography Mass Spectrometry metabolomics was used to identify and confirm metabolites disrupted in the blood of Lassa fever and Ebola patients. Authenticated standards are used to confirm the identify of key metabolites.

Results

We confirm prior results by other investigators that the amino acid l-threonine is elevated during Ebola virus infection. l-Threonine is also elevated during Lassa virus infection. We also confirmed that platelet-activating factor (PAF) and molecules with PAF moiety are reduced in the blood of patients with fatal Lassa fever. Similar changes in PAF and PAF-like molecules were not observed in the blood of Ebola patients.

Conclusions

Metabolomics may provide tools to identify pathways that are differentially affected during viral hemorrhagic fevers and guide development of diagnostics to monitor and predict outcome.
Neuropathology changed by 3- and 6-months low-level PM2.5 inhalation exposure in spontaneously hypertensive rats
Authors: Chuang Hsiao-Chi , Chen Hsin-Chang , Chai Pei-Jui , Liao Ho-Tang , Wu Chang-Fu , Chen Chia-Ling , Jhan Ming-Kai , Hsieh Hui-I , Wu Kuen-Yuh , Chen Ta-Fu , Cheng Tsun-Jen
Published: November 2020

Background

Epidemiological evidence has linked fine particulate matter (PM2.5) to neurodegenerative diseases; however, the toxicological evidence remains unclear. The objective of this study was to investigate the effects of PM2.5 on neuropathophysiology in a hypertensive animal model. We examined behavioral alterations (Morris water maze), lipid peroxidation (malondialdehyde (MDA)), tau and autophagy expressions, neuron death, and caspase-3 levels after 3 and 6 months of whole-body exposure to urban PM2.5 in spontaneously hypertensive (SH) rats.

Results

SH rats were exposed to S-, K-, Si-, and Fe-dominated PM2.5 at 8.6 ± 2.5 and 10.8 ± 3.8 μg/m3 for 3 and 6 months, respectively. We observed no significant alterations in the escape latency, distance moved, mean area crossing, mean time spent, or mean swimming velocity after PM2.5 exposure. Notably, levels of MDA had significantly increased in the olfactory bulb, hippocampus, and cortex after 6 months of PM2.5 exposure (p < 0.05). We observed that 3 months of exposure to PM2.5 caused significantly higher expressions of t-tau and p-tau in the olfactory bulb (p < 0.05) but not in other brain regions. Beclin 1 was overexpressed in the hippocampus with 3 months of PM2.5 exposure, but significantly decreased in the cortex with 6 months exposure to PM2.5. Neuron numbers had decreased with caspase-3 activation in the cerebellum, hippocampus, and cortex after 6 months of PM2.5 exposure.

Conclusions

Chronic exposure to low-level PM2.5 could accelerate the development of neurodegenerative pathologies in subjects with hypertension.
Multiloop edgewise archwire technique and denture frame analysis: a systematic review
Authors: Tabancis M. , Ratzmann A. , Doberschütz P. , Krey K. F.
Published: November 2020

Background

The Multiloop Edgewise Archwire (MEAW) appliance is an orthodontic treatment method suitable for the therapy of severe types of malocclusions such as open bites or anterior crossbites. The cephalometric Denture Frame Analysis (DFA) provides a supportive diagnostic tool for patient-specific treatment planning concerning the rearrangement of occlusion within the “denture frame”. The objective of this study is to give a comprehensive overview of the national and international scientific literature about MEAW and DFA regarding the general therapeutic effects, advantages and limitations.

Methods and materials

A computerized literature search was performed using four principal medical databases (PubMed/Medline, Google Scholar, Web of Science and Cochrane Central Register of Controlled Trials) and supplemented by manual searching of the references listed in the retrieved articles. The results were screened and assessed following the PRISMA guidelines.

Results

Six hundred seventy-seven full articles were assessed for eligibility. A number of 134 articles went through qualitative analysis and 3 studies were finally involved in comparative synopsis. The findings reveal advantageous characteristics of the MEAW technique such as a high degree of three-dimensional individual tooth control and a comparatively low load deflection rate, causing mostly dentoalveolar changes without significantly influencing the skeletal structures.

Conclusion

Based on current literature, the MEAW technique appears to have several therapeutic benefits and serves as a sufficient alternative treatment method for dentoalveolar compensation, when measures of orthognathic surgery are rejected. Concerning the deficient data basis of available literature and the low level of scientific evidence, further studies are required in order to expand on the knowledge in this subject area. Several aspects like the effectiveness or the long-term stability have to be evaluated more extensively. Moreover, the transferability of the DFA to ethnic groups other than the Asian ethnicity should be examined further.
Correction to: A new 3D printing porous trabecular titanium metal acetabular cup for primary total hip arthroplasty: a minimum 2-year follow-up of 92 consecutive patients
Authors: Geng Xiao , Li Yang , Li Feng , Wang Xinguang , Zhang Ke , Liu Zhongjun , Tian Hua
Published: November 2020

An amendment to this paper has been published and can be accessed via the original article.
High output cardiac failure in 3 patients with hereditary hemorrhagic telangiectasia and hepatic vascular malformations, evaluation of treatment
Authors: Olsen Lilian B. , Kjeldsen Anette D. , Poulsen Mikael K. , Kjeldsen Jens , Fialla Annette D.
Published: November 2020

Background

This report addresses how patients with hereditary hemorrhagic telangiectasia (HHT) and high output cardiac failure (HOCF) due to hepatic vascular malformations, should be evaluated and could be treated. HHT is a genetic disorder, leading to vascular abnormalities with potentially serious clinical implications. In the liver, arteriovenous malformations occur in more than 70% of patients, but only about 8% present clinical symptoms such as HOCF with pulmonary hypertension and less commonly portal hypertension, biliary ischemia and hepatic encephalopathy.

Results

Three female patients with HHT type 2 and HOCF caused by severe arteriovenous malformations in the liver are presented in this case series. The patients were seen at the HHT-Centre at Odense University Hospital. Treatment with either orthotopic liver transplantation (one patient) or bevacizumab (two patients) was initiated. All patients experienced marked symptom relief and objective improvement. New York Heart Association—class were improved, ascites, peripheral edema and hence diuretic treatment was markedly reduced or discontinued in all three patients. Bevacizumab also resulted in notable effects on epistaxis and anemia.

Conclusion

Our findings substantiate the importance of identification of symptomatic arteriovenous malformations in the liver in patients with HHT. Bevacizumab may possibly, as suggested in this case series and supported by previous case studies, postpone the time to orthotopic liver transplantation or even make it unnecessary. Bevacizumab represents a promising new treatment option, which should be investigated further in clinical trials.
The genetic landscape of crystallins in congenital cataract
Authors: Berry Vanita , Ionides Alex , Pontikos Nikolas , Georgiou Michalis , Yu Jing , Ocaka Louise A. , Moore Anthony T. , Quinlan Roy A. , Michaelides Michel
Published: November 2020

Background

The crystalline lens is mainly composed of a large family of soluble proteins called the crystallins, which are responsible for its development, growth, transparency and refractive index. Disease-causing sequence variants in the crystallins are responsible for nearly 50% of all non-syndromic inherited congenital cataracts, as well as causing cataract associated with other diseases, including myopathies. To date, more than 300 crystallin sequence variants causing cataract have been identified.

Methods

Here we aimed to identify the genetic basis of disease in five multi-generation British families and five sporadic cases with autosomal dominant congenital cataract using whole exome sequencing, with identified variants validated using Sanger sequencing. Following bioinformatics analysis, rare or novel variants with a moderate to damaging pathogenicity score, were filtered out and tested for segregation within the families.

Results

We have identified 10 different heterozygous crystallin variants. Five recurrent variants were found: family-A, with a missense variant (c.145C>T; p.R49C) in CRYAA associated with nuclear cataract; family-B, with a deletion in CRYBA1 (c.272delGAG; p.G91del) associated with nuclear cataract; and family-C, with a truncating variant in CRYGD (c.470G>A; W157*) causing a lamellar phenotype; individuals I and J had variants in CRYGC (c.13A>C; T5P) and in CRYGD (c.418C>T; R140*) causing unspecified congenital cataract and nuclear cataract, respectively. Five novel disease-causing variants were also identified: family D harboured a variant in CRYGC (c.179delG; R60Qfs*) responsible for a nuclear phenotype; family E, harboured a variant in CRYBB1 (c.656G>A; W219*) associated with lamellar cataract; individual F had a variant in CRYGD (c.392G>A; W131*) associated with nuclear cataract; and individuals G and H had variants in CRYAA (c.454delGCC; A152del) and in CRYBB1 (c.618C>A; Y206*) respectively, associated with unspecified congenital cataract. All novel variants were predicted to be pathogenic and to be moderately or highly damaging.

Conclusions

We report five novel variants and five known variants. Some are rare variants that have been reported previously in small ethnic groups but here we extend this to the wider population and record a broader phenotypic spectrum for these variants.
Investigation of bovine ephemeral fever virus transmission by putative dipteran vectors under experimental conditions
Authors: Stokes Jessica E. , Darpel Karin E. , Gubbins Simon , Carpenter Simon , Fernández de Marco María del Mar , Hernández-Triana Luis M. , Fooks Anthony R. , Johnson Nicholas , Sanders Christopher
Published: November 2020

Background

Bovine ephemeral fever virus (Rhabdoviridae: Ephemerovirus) (BEFV) causes bovine ephemeral fever (BEF), an economically important disease of cattle and water buffalo. Outbreaks of BEF in Africa, Australia, Asia and the Middle East are characterized by high rates of morbidity and highly efficient transmission between cattle hosts. Despite this, the vectors of BEFV remain poorly defined.

Methods

Colony lines of biting midges (Culicoides sonorensis) and mosquitoes (Aedes aegypti, Culex pipiens and Culex quinquefasciatus) were infected with a strain of BEFV originating from Israel by feeding on blood–virus suspensions and by intrathoracic inoculation. In addition, in vivo transmission of BEFV was also assessed by allowing C. sonorensis inoculated by the intrathoracic route to feed on male 6 month-old Holstein-Friesian calves.

Results

There was no evidence of BEFV replication within mosquitoes fed on blood/virus suspensions for mosquitoes of any species tested for each of the three colony lines. In 170 C. sonorensis fed on the blood/virus suspension, BEFV RNA was detected in the bodies of 13 individuals and in the heads of two individuals, indicative of fully disseminated infections and an oral susceptibility rate of 1.2%. BEFV RNA replication was further demonstrated in all C. sonorensis that were inoculated by the intrathoracic route with virus after 5, 6 or 7 days post-infection. Despite this, transmission of BEFV could not be demonstrated when infected C. sonorensis were allowed to feed on calves.

Conclusions

No evidence for infection or dissemination of BEFV (bovine/Israel/2005-6) in mosquitoes of three different species was found. Evidence was found for infection of C. sonorensis by the oral route. However, attempts to transmit BEFV to calves from infected C. sonorensis failed. These results highlight the challenge of defining the natural vector of BEFV and of establishing an in vivo transmission model. The results are discussed with reference to the translation of laboratory-based studies to inference of vector competence in the field.

Graphical abstract
Correction to: Evaluation of the impact of six different DNA extraction methods for the representation of the microbial community associated with human chronic wound infections using a gel‑based DNA profiling method
Authors: Dilhari Ayomi , Sampath Asanga , Gunasekara Chinthika , Fernando Neluka , Weerasekara Deepaka , Sissons Chris , McBain Andrew , Weerasekera Manjula
Published: November 2020

An amendment to this paper has been published and can be accessed via the original article.
Informant-based screening tools for diagnosis of dementia, an overview of systematic reviews of test accuracy studies protocol
Authors: Taylor-Rowan Martin , Nafisi Sara , Patel Amit , Burton Jennifer K. , Quinn Terry J.
Published: November 2020

Background

Robust diagnosis of dementia requires an understanding of the accuracy of the available diagnostic tests. Informant questionnaires are frequently used to assess for dementia in clinical practice. Recent systematic reviews have sought to establish the diagnostic test accuracy of various dementia informant screening tools. However, most reviews to date have focused on a single diagnostic tool and this does not address which tool is ‘best’. A key aim of the overview of systematic reviews is to present a disparate evidence base in a single, easy to access platform.

Methods

We will conduct an overview of systematic reviews in which we ‘review the systematic reviews’ of diagnostic test accuracy studies evaluating informant questionnaires for dementia. As an overview of systematic reviews of test accuracy is a relatively novel approach, we will use this review to explore methods for visual representation of complex data, for highlighting evidence gaps and for indirect comparative analyses. We will create a list of informant tools by consulting with dementia experts. We will search 6 databases (EMBASE (OVID); Health and Psychosocial Instruments (OVID); Medline (OVID); CINAHL (EBSCO); PSYCHinfo (EBSCO) and the PROSPERO registry of review protocols) to identify systematic reviews that describe the diagnostic test accuracy of informant questionnaires for dementia. We will assess review quality using the AMSTAR-2 (Assessment of Multiple Systematic Reviews) and assess reporting quality using PRISMA-DTA (Preferred Reporting Items for Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies) checklists. We will collate the identified reviews to create an ‘evidence map’ that highlights where evidence does and does not exist in relation to informant questionnaires. We will pool sensitivity and specificity data via meta-analysis to generate a diagnostic test accuracy summary statistic for each informant questionnaire. If data allow, we will perform a statistical comparison of the diagnostic test accuracy of each informant questionnaire using a network approach.

Discussion

Our overview of systematic reviews will provide a concise summary of the diagnostic test accuracy of informant tools and highlight areas where evidence is currently lacking in this regard. It will also apply network meta-analysis techniques to a new area.
A guide for pre-procedural imaging for transcatheter aortic valve replacement patients
Authors: Perry Tjörvi E. , George Stephen A. , Lee Belinda , Wahr Joyce , Randle Darrell , Sigurðsson Garðar
Published: November 2020

Safe and accurate pre-procedural assessment of cardiovascular anatomy, physiology, and pathophysiology prior to TAVR procedures can mean the difference between success and catastrophic failure. It is imperative that clinical care team members share a basic understanding of the preprocedural imaging technologies available for optimizing the care of TAVR patients. Herein, we review current imaging technology for assessing the anatomy, physiology, and pathophysiology of the aortic valvular complex, ventricular function, and peripheral vasculature, including echocardiography, cardiac catheterization, cardiac computed tomography, and cardiac magnetic resonance prior to a TAVR procedure. The authorship includes cardiac-trained anesthesiologists, anesthesiologists with expertise in pre-procedural cardiac assessment and optimization, and interventional cardiologists with expertise in cardiovascular imaging prior to TAVRs. Improving the understanding of all team members will undoubtedly translate into safer, more coordinated patient care.
Flight delay prediction based on deep learning and Levenberg-Marquart algorithm
Authors: Yazdi Maryam Farshchian , Kamel Seyed Reza , Chabok Seyyed Javad Mahdavi , Kheirabadi Maryam
Published: November 2020

Flight delay is inevitable and it plays an important role in both profits and loss of the airlines. An accurate estimation of flight delay is critical for airlines because the results can be applied to increase customer satisfaction and incomes of airline agencies. There have been many researches on modeling and predicting flight delays, where most of them have been trying to predict the delay through extracting important characteristics and most related features. However, most of the proposed methods are not accurate enough because of massive volume data, dependencies and extreme number of parameters. This paper proposes a model for predicting flight delay based on Deep Learning (DL). DL is one of the newest methods employed in solving problems with high level of complexity and massive amount of data. Moreover, DL is capable to automatically extract the important features from data. Furthermore, due to the fact that most of flight delay data are noisy, a technique based on stack denoising autoencoder is designed and added to the proposed model. Also, Levenberg-Marquart algorithm is applied to find weight and bias proper values, and finally the output has been optimized to produce high accurate results. In order to study effect of stack denoising autoencoder and LM algorithm on the model structure, two other structures are also designed. First structure is based on autoencoder and LM algorithm (SAE-LM), and the second structure is based on denoising autoencoder only (SDA). To investigate the three models, we apply the proposed model on U.S flight dataset that it is imbalanced dataset. In order to create balance dataset, undersampling method are used. We measured precision, accuracy, sensitivity, recall and F-measure of the three models on two cases. Accuracy of the proposed prediction model analyzed and compared to previous prediction method. results of three models on both imbalanced and balanced datasets shows that precision, accuracy, sensitivity, recall and F-measure of SDA-LM model with imbalanced and balanced dataset is improvement than SAE-LM and SDA models. The results also show that accuracy of the proposed model in forecasting flight delay on imbalanced and balanced dataset respectively has greater than previous model called RNN.
Relative validity of a brief dietary survey to assess food intake and adherence to national dietary guidelines among Sri Lankan adults
Authors: Renzella J. , Fernando S. , Kalupahana B. , Townsend N. , Rayner M. , Wickramasinghe K. , Katulanda P. , Scarborough P.
Published: November 2020

Background

Suboptimal diet is the leading cause of global morbidity and mortality. Addressing this problem requires context-specific solutions informed by context-specific data collected by context-specific tools. This study aimed to assess the relative validity of a newly developed brief dietary survey to estimate food intake and adherence to the Food Based Dietary Guidelines for Sri Lankans.

Methods

Between December 2018 and February 2019, we interviewed 94 Sri Lankan adults living in Colombo (Western Province), Kalutara (Western Province), and Trincomalee (Eastern Province). We assessed the relative validity of the Sri Lankan Brief Dietary Survey (SLBDS) with Wilcoxon rank-sum tests, Spearman’s Rho correlation coefficients, Bland–Altman plots, and Cohen’s kappa tests using a 24-h Dietary Recall (24DR) as reference.

Results

Ninety-four adults (40.7 years ±12.6; 66% female) completed both surveys during the same interview. With the exception of ‘Fish, pulses, meat and eggs’ food group median intake, which was underestimated by the SLBDS compared to the 24DR, there was no strong evidence of difference between median intakes reported by the two methods. Correlation coefficients were highest for ‘Milk and dairy products’ (0.84) at the food group level and for ‘dosa’, ‘hoppers’, ‘milk rice’, and ‘dried fish’ (1.00) among individual food and beverages. Visual exploration of Bland-Altman plots showed acceptable agreement between the SLBDS and 24DR, with the SLBDS tending to overestimate consumption as the number of servings of ‘Rice, bread, other cereals and yams’ and ‘Vegetables’ consumed increased and slightly underestimate consumption as the number of servings of ‘Fish, pulses, meat and eggs’, ‘Milk and dairy products’, and ‘Nuts’ increased. Kappa values ranged from from 0.59 (95% CI: 0.32–0.86) for ‘Vegetables’ to 0.81 (95% CI: 0.66–0.96) for ‘Fruit’ indicating a moderate to strong level of agreement.

Conclusions

Having been developed for and relatively validated with the study population in question, our study shows that the SLBDS can be used as a fit for purpose research tool. Additional research is needed to assess SLBDS test-retest reliability and to validate further the reporting of salt, oil, and coconut intake.
Atypical benzodiazepine misuse and withdrawal in patient with epilepsy: a case report
Authors: Piskorska Natalia , Silczuk Andrzej
Published: November 2020

Background

Benzodiazepines (BDZ) are a class of psychoactive drugs that have been widely used for the treatment of many medical conditions. In this paper, a case of an atypical pattern of diazepam dependence in a patient with epilepsy is presented. The article may be an interesting proposition for rational management in the treatment of benzodiazepine dependence in a patient with non-withdrawal and withdrawal seizures. Detoxification is used then to optimize neurological treatment.

Case presentation

A 52-year-old Caucasian male, diagnosed with epilepsy with partial complex, and rarely tonic-clonic seizures and benzodiazepine (diazepam) misuse, was admitted to a detoxification unit specialized to treat substance dependence. This patient presented an atypical schedule of substance misuse with a weekly dose of 40 to 45 mg of diazepam, taken once a week, every Saturday. The patient reported having a group of symptoms that usually preceded generalized seizures that were described as the “aura” manifesting as confusion, derealisation, anxiety, and difficulties in speaking. First Saturday after admission to the hospital, the first aura experience was reported, while diazepam level in serum was higher than usual, which was supporting also strong psychological background for withdrawal. On weekend days, 3 weeks after admission, when the patient was receiving 3 mg of diazepam daily, he developed a severe “aura.” The EEG showed no seizure activity. Two weeks later (again Friday to Saturday), the patient reported the occurrence of aura, the EEG recording showed paroxysmal discharges, generalized multiple spikes associated with slow waves, lasting about 30 s, accompanied by eyelid myoclonia and disturbed consciousness. A week later another aura developed that resolved spontaneously without a seizure. Twelve days later, diazepam was completely removed; the elimination of serum benzodiazepines took place. The patient did not report aura until the end of the stay and he was dismissed 5 weeks later.

Conclusions

The differential diagnosis of an aura can be challenging. Carefully proceed serum monitored elimination of benzodiazepines in epileptic patients may serve in safety benefits and helps to achieve detoxification goals. Hence, it is important to prevent, recognize, and treat benzodiazepine dependence in every patient and may improve epilepsy treatment outcome.
Large-eddy simulation of wall-bounded turbulent flow with high-order discrete unified gas-kinetic scheme
Authors: Zhang Rui , Zhong Chengwen , Liu Sha , Zhuo Congshan
Published: November 2020

In this paper, we introduce the discrete Maxwellian equilibrium distribution function for incompressible flow and force term into the two-stage third-order Discrete Unified Gas-Kinetic Scheme (DUGKS) for simulating low-speed turbulent flows. The Wall-Adapting Local Eddy-viscosity (WALE) and Vreman sub-grid models for Large-Eddy Simulations (LES) of turbulent flows are coupled within the present framework. Meanwhile, the implicit LES are also presented to verify the effect of LES models. A parallel implementation strategy for the present framework is developed, and three canonical wall-bounded turbulent flow cases are investigated, including the fully developed turbulent channel flow at a friction Reynolds number (Re) about 180, the turbulent plane Couette flow at a friction Re number about 93 and lid-driven cubical cavity flow at a Re number of 12000. The turbulence statistics, including mean velocity, the r.m.s. fluctuations velocity, Reynolds stress, etc. are computed by the present approach. Their predictions match precisely with each other, and they are both in reasonable agreement with the benchmark data of DNS. Especially, the predicted flow physics of three-dimensional lid-driven cavity flow are consistent with the description from abundant literature. The present numerical results verify that the present two-stage third-order DUGKS-based LES method is capable for simulating inhomogeneous wall-bounded turbulent flows and getting reliable results with relatively coarse grids.
High order semi-implicit weighted compact nonlinear scheme for the all-Mach isentropic Euler system
Authors: Jiang Yanqun , Chen Xun , Zhang Xu , Xiong Tao , Zhou Shuguang
Published: November 2020

The computation of compressible flows at all Mach numbers is a very challenging problem. An efficient numerical method for solving this problem needs to have shock-capturing capability in the high Mach number regime, while it can deal with stiffness and accuracy in the low Mach number regime. This paper designs a high order semi-implicit weighted compact nonlinear scheme (WCNS) for the all-Mach isentropic Euler system of compressible gas dynamics. To avoid severe Courant-Friedrichs-Levy (CFL) restrictions for low Mach flows, the nonlinear fluxes in the Euler equations are split into stiff and non-stiff components. A third-order implicit-explicit (IMEX) method is used for the time discretization of the split components and a fifth-order WCNS is used for the spatial discretization of flux derivatives. The high order IMEX method is asymptotic preserving and asymptotically accurate in the zero Mach number limit. One- and two-dimensional numerical examples in both compressible and incompressible regimes are given to demonstrate the advantages of the designed IMEX WCNS.
An overview of recent progress in modern synthetic approach—combinatorial synthesis
Authors: Gopi Chandravadivelu , Krupamai Gudapati , Sri Chitikina Satya , Dhanaraju Magharla Dasaratha
Published: November 2020

Background

In recent times, a powerful tool of combinatorial synthesis has been used for the preparation of large chemical entities through a small set up of reactions between different building blocks using solid-phase and solution-phase techniques. This method reduced the time and cost of the drug discovery process substantially.

Main text

Thousands of compounds are synthesised in a few reactions through combinatorial synthesis instead of getting a few compounds in the traditional method. This method also helps to identify chemical lead of the compounds and optimise them through the biological screening using a high-throughput method. There is no review concerning the recent research finding of combinatorial synthesis. Hence, an attempt had been made on the latest research findings (2002–2020) of newly synthesised compounds using combinatorial synthesis and their biological activities.

Conclusion

To the best of our knowledge, the current review has completely analysed the importance of combinatorial synthesis and furnished an overview of solid-phase and solution-phase techniques as well as helped mankind by improving higher productivity at low cost, lead identification and optimization and preventing environmental pollution.

Graphical abstract
Red blood cell carbonic anhydrase mediates oxygen delivery via the Root effect in red drum
Authors: Dichiera Angelina M. , Esbaugh Andrew J.
Published: November 2020

Oxygen (O2) and carbon dioxide (CO2) transport are tightly coupled in many fishes as a result of the presence of Root effect hemoglobins (Hb), whereby reduced pH reduces O2 binding even at high O2 tensions. Red blood cell carbonic anhydrase (RBC CA) activity limits the rate of intracellular acidification, yet its role in O2 delivery has been downplayed. We developed an in vitro assay to manipulate RBC CA activity while measuring Hb-O2 offloading following a physiologically relevant CO2-induced acidification. RBC CA activity in red drum (Sciaenops ocellatus) was inhibited with ethoxzolamide by 53.7±0.5%, which prompted a significant reduction in O2 offloading rate by 54.3±5.4% (P=0.0206, two-tailed paired t-test; n=7). Conversely, a 2.03-fold increase in RBC CA activity prompted a 2.14-fold increase in O2 offloading rate (P<0.001, two-tailed paired t-test; n=8). This approximately 1:1 relationship between RBC CA activity and Hb-O2 offloading rate coincided with a similar allometric scaling exponent for RBC CA activity and maximum metabolic rate. Together, our data suggest that RBC CA is rate limiting for O2 delivery in red drum.
Chiral Guanidine Catalyzed Acylative Kinetic Resolution of Racemic 2-Bromo-1-arylethanols
Authors: Sawada Erika , Nakata Kenya
Published: November 2020

In this study, chiral guanidine catalyzed acylative kinetic resolution of racemic 2-bromo-1-arylethanols was achieved with high selectivity. Irrespective of the electronic nature and the substitution patterns on the aromatic rings, a variety of substrates were suitable for this reaction. The branched acyl component was considered to be optimal for obtaining high s-values. The transition state of the reaction was proposed based on the absolute configuration of the obtained product.
First report of Serratia marcescens associated with black rot of Citrus sinensis fruit, and evaluation of its biological control measures in Bangladesh
Authors: Hasan Mohammed Faruk , Islam Mohammed Asadul , Sikdar Biswanath
Published: November 2020

Background: The present study was designed to isolate and identify the phyto-pathogen responsible for black rot of Citrus sinensis, and to determine its biological control measures.

Methods: The pathogen was isolated from infected oranges and cultured on Luria-Bertani medium. Gram staining method was used to identify the morphological characteristics of the causal agents of the black rot. Advanced molecular technique was applied to facilitate proper detection of the isolated bacteria. Phylogenetic trees were analyzed using the Neighbor-Joining method. Antimicrobial screening was conducted by disc diffusion method. Antagonistic activity was evaluated by well diffusion method.

Results: Gram staining of the causal agent showed rod shaped, small and pink bacteria. Polymerase chain reaction of the 16S ribosomal RNA gene amplified an approximately 1465 bp product. The nucleotide sequences of the isolated bacterial sample 1 (BS1) and bacterial sample 2 (BS2) had 99.34% and 99.45% similarities with the reference of Serratia marcescens sequence in NCBI GenBank. The obtained sequences were deposited in GenBank. Two isolates showed virulence capability on some fresh fruits, which confirmed the stain detection and Koch’s postulates. Allium sativum extract showed the largest (27.33±1.5 mm) diameter of zone of inhibition against BS1, at 30µg/disc concentration. In the antagonistic assay, Rhizobium leguminosarum showed largest (19±1 mm) zone of inhibition against BS1.

Conclusions: Findings of the current investigations are constructive for identification of causative pathogens in Citrus sinensis black rot disease and their biological control measures.
The Avon Longitudinal Study of Parents and Children - A resource for COVID-19 research: Generation 2 questionnaire data capture May-July 2020
Authors: Smith Daniel , Northstone Kate , Bowring Claire , Wells Nicholas , Crawford Michael , Pearson Rebecca M. , Thomas Amy , Brooks-Pollock Ellen , Lawlor Deborah A. , Timpson Nicholas John
Published: November 2020

The Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective population-based cohort study which recruited pregnant women in 1990-1992 from the Bristol area (UK). ALSPAC has followed these women, their partners (Generation 0; G0) and their offspring (Generation 1; G1) ever since. From 2012, ALSPAC has identified G1 participants who were pregnant (or their partner was) or had become parents, and enrolled them, their partners, and children in the ALSPAC-Generation 2 (ALSPAC-G2) study, providing a unique multi-generational cohort. At present, approximately 1,100 G2 children (excluding thosein utero) from 810 G1 participants have been enrolled.

In response to the COVID-19 pandemic, ALSPAC rapidly deployed two online questionnaires; one during the initial lockdown phase in 2020 (9thApril-15thMay), and another when national lockdown restrictions were eased (26thMay-5thJuly). As part of this second questionnaire, G1 parents completed a questionnaire about each of their G2 children. This covered: parental reports of children’s feelings and behaviour since lockdown, school attendance, contact patterns, and health. A total of 289 G1 participants completed this questionnaire on behalf of 411 G2 children.

This COVID-19 G2 questionnaire data can be combined with pre-pandemic ALSPAC-G2 data, plus ALSPAC-G1 and -G0 data, to understand how children’s health and behaviour has been affected by the pandemic and its management. Data from this questionnaire will be complemented with linkage to health records and results of biological testing as they become available. Prospective studies are necessary to understand the impact of this pandemic on children’s health and development, yet few relevant studies exist; this resource will aid these efforts.

Data has been released as: 1) a freely-available dataset containing participant responses with key sociodemographic variables; and 2) an ALSPAC-held dataset which can be combined with existing ALSPAC data, enabling bespoke research across all areas supported by the study.