bluuebunny/crossref_metadata_2025 huggingface dataset:
“Go and Wash up!”: Gender Violence in Female Refereeing and Its Media Coverage in Brazil and Spain
Authors: Marín-Montín Joaquín , Bianchi Paula
Published: November 2022

Violence in sports has the greatest impact in the media, especially on television. In the case of refereeing, although there are studies that have specifically addressed violence, those performed on female referees have not had the same repercussions. Accordingly, the aim of this paper is to analyse the media coverage of violence against female referees in Brazil and Spain. In parallel, its intention is to reflect the perceptions of female referees in this respect. The methodology employed combined case studies with critical discourse analysis, based on news items and focus groups with female referees. The results reveal that gender violence against female referees is the most widespread type of aggression. Moreover, they highlight the sensationalist nature of the TV coverage of the phenomenon through the incorporation of visual and audio resources. Lastly, the findings of this study show how the prominence that this type of violence has achieved in the media has ended up eclipsing the recognition of the work of female referees.
Trends in prevalence of self-reports of Alzheimer’s disease/dementia among non-institutionalized individuals 45+ in Canada, 1994–2014
Authors: Chambers-Richards Tamara , Chireh Batholomew , D’Arcy Carl
Published: November 2022

Background:

Alzheimer’s disease/dementia (AD) prevalence is of concern globally and in Canada owing to the rapidly aging population and increase in life expectancy. This study explored: (1) trends in the overall prevalence of self-reported AD/dementia by sex, age groups, educational levels, and geographic areas in Canada from 1994 to 2014, and (2) assessed what the observed trends mean in the context of the aging Canadian population and the health care system.

Design and methods:

This cross-sectional study used Canadian national survey data. Data for this study were from two Canadian national health surveys (National Population Health Survey and the Canadian Community Health Survey), between 1994 and 2014. After age-sex standardization, trends in the prevalence of self-reported Alzheimer’s disease/dementia were tracked over time. The two cross-sectional surveys used similar diagnostic criteria over the years.

Results:

The overall prevalence of Alzheimer’s disease/dementia increased from 0.14 in 1994 to 0.80 in 2014 representing a 0.66-point increase over the 20 years. Alzheimer’s disease/dementia prevalence increased with age across all years but was more pronounced after age 80. Men 65+ years, those with lower education, and Canadians living in Central Canada had an increased prevalence.

Conclusions:

The overall prevalence of Alzheimer’s disease/dementia in the community increased over time. This study highlights the importance of establishing effective community-based prevention strategies that focus on minimizing risk and optimizing protection as well as health system capacity strengthening and preparation for long-term care including increased demand for neurologists’ services, increased associated disability, psychosocial difficulties, rising costs, and caregiver burden.
MRI Does Not Reliably Detect Kaplan Fiber Injury In Skeletally Immature Patients with an Acute ACL Tear
Authors: Lynch Thomas B. , Swan Erin R. , Cognetti Daniel , Arana Mireles Allyson , Byerly Douglas , Bernot Jeremy M. , Cecava Nathan D. , Chasteen Jesse , Musahl Volker , Schmitz Matthew R. , Sheean Andrew J.
Published: November 2022

Background:

To our knowledge, there have been no previous efforts to evaluate the prevalence of Kaplan fiber (KF) injury in skeletally immature patients with an acute anterior cruciate ligament (ACL) tear on magnetic resonance imaging (MRI) nor has there been any comparison of the reliability of previously described KF diagnostic criteria in this cohort.

Purpose:

To define the prevalence of KF injury in the setting of acute ACL tears using MRI performed within 90 days of injury among skeletally immature patients, and to compare the reliability of MRI in detecting KF injuries using 2 previously described diagnostic criteria.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

Skeletally immature patients with an acute ACL tear confirmed using MRI within 90 days of injury were assessed. Two fellowship-trained musculoskeletal radiologists independently interpreted each MRI scan twice. KF injury was first assessed using the Van Dyck scheme (grade 0, normal; grade 1, periligamentous; grade 2, partial tear; and grade 3, complete tear). MRI scans were then reviewed again using the KF injury criteria proposed by Batty. Discrepancies in KF injury schemes were adjudicated by a third musculoskeletal radiologist. Interrater agreement for both methods was determined using Cohen κ.

Results:

Included were 45 patients (33 male, 12 female) with a mean age of 13.2 ± 1.6 years. KF injuries were identified in 17 of 45 (37.7%) knees of using the traditional Van Dyck grading scheme (interrater agreement κ = 0.40). The Batty diagnostic criteria identified KF injury in 5 of 45 (11.1%) (interrater agreement κ = 0.45); 17 (37.8%) MRI scans required a third reviewer adjudication for the Van Dyck scheme, while 4 (8.9%) required a third reviewer using the Batty criteria.

Conclusion:

The Batty diagnostic criteria detected a lower KF injury prevalence than previously reported in the adult population, while the Van Dyck prevalence was similar to rates in adult populations. Both grading criteria had poor interrater reliability in diagnosing a KF injury.
Interdisciplinarity can aid the spread of better methods between scientific communities
Authors: Smaldino Paul E , O’Connor Cailin
Published: November 2022

Why do bad methods persist in some academic disciplines, even when they have been widely rejected in others? What factors allow good methodological advances to spread across disciplines? In this paper, we investigate some key features determining the success and failure of methodological spread between the sciences. We introduce a formal model that considers factors like methodological competence and reviewer bias toward one’s own methods. We show how these self-preferential biases can protect poor methodology within scientific communities, and lack of reviewer competence can contribute to failures to adopt better methods. We then use a second model to argue that input from outside disciplines can help break down barriers to methodological improvement. In doing so, we illustrate an underappreciated benefit of interdisciplinarity.
Minimally Invasive Esophagectomy for End-Stage Achalasia: A Single Institution Experience and Literature Review
Authors: Torres-Landa Samuel , Jones Amy E. , Crafts Trevor D. , Qureshi Alia , Wood Stephanie G.
Published: November 2022

Background:

Surgical outcomes after minimally invasive esophagectomy (MIE) for patients with end-stage achalasia are limited. This study presents a case series of end-stage achalasia patients who underwent MIE at a high-volume institution and review of the literature.

Methods:

We conducted a retrospective review of a single academic institution from 2010 to 2019. Patients with end-stage achalasia who underwent a MIE were included. Descriptive statistics for demographics as well as 90-day surgical outcomes (length of stay, readmission, reoperation, overall complications, and mortality) were included.

Results:

A total of 16 patients underwent MIE for achalasia during the study period, 14 (87.5%) 3-field and 2 (12.5%) trans-hiatal esophagectomies. The mean age was 52.5 (SD ± 10.5) years and 56.3% (9/16) were women. Mean operative time was 456.6 (SD ± 83.96) minutes. Within 90-days, the overall complication rate was 50% (8 patients). Of these complications, 4 had minor complications (Clavian-Dindo Grade I and II) and 4 had complications that required further interventions (Clavian-Dindo Grade ≥ III). Four (26.7%) patients were readmitted, 3 (18.8%) patients required reoperation, and 1 (6.3%) had an anastomotic leak. The reasons for reoperation included: 1 anastomotic leak, 1 chyle leak, and 1 incarcerated paraconduit hernia. No mortalities occurred.

Conclusion:

MIE should be considered for end-stage achalasia only as a last resort for patients with debilitating symptoms. While mortality was low, overall complications were high, even at a high-volume institution.
The capability of ABAQUS/CAE to predict the tensile properties of sisal fiber reinforced polyethylene terephthalate composites
Authors: Gudayu Adane Dagnaw , Steuernagel Leif , Meiners Dieter
Published: November 2022

Plastics reinforced by natural fibers attract growing attention, particularly in the automotive industry. The properties and performance of these composites are usually determined before application. However, many mechanical tests of composite materials are destructive, expensive, time-consuming, and can cause operator fatigue. The objective of this research is to model the tensile properties of sisal fiber reinforced polyethylene terephthalate (PET) composites and compare the model outcomes with the results of experimental tests. For the experiment, PET was reinforced with 25% wt. of sisal fiber and composite samples were produced by compounding and injection molding processes. Modeling and simulation have also been carried out with ABAQUS/CAE software. The outputs on the tensile properties of the experiment and the model were statistically compared to see the accuracy of the model against the experimental results. The two-sample t-test indicates that, at 95% confidence interval, the mean differences for the stress, strain, and modulus for the experimental tests and the model results are not significantly different from zero. The research shows that the experiment can be effectively modeled with ABAQUS-based modeling and simulation techniques by linking with appropriate mathematical predictive models.
SparkEC: speeding up alignment-based DNA error correction tools
Authors: Expósito Roberto R. , Martínez-Sánchez Marco , Touriño Juan
Published: November 2022

Background

In recent years, huge improvements have been made in the context of sequencing genomic data under what is called Next Generation Sequencing (NGS). However, the DNA reads generated by current NGS platforms are not free of errors, which can affect the quality of downstream analysis. Although error correction can be performed as a preprocessing step to overcome this issue, it usually requires long computational times to analyze those large datasets generated nowadays through NGS. Therefore, new software capable of scaling out on a cluster of nodes with high performance is of great importance.

Results

In this paper, we present SparkEC, a parallel tool capable of fixing those errors produced during the sequencing process. For this purpose, the algorithms proposed by the CloudEC tool, which is already proved to perform accurate corrections, have been analyzed and optimized to improve their performance by relying on the Apache Spark framework together with the introduction of other enhancements such as the usage of memory-efficient data structures and the avoidance of any input preprocessing. The experimental results have shown significant improvements in the computational times of SparkEC when compared to CloudEC for all the representative datasets and scenarios under evaluation, providing an average and maximum speedups of 4.9$$\times$$×and 11.9$$\times$$×, respectively, over its counterpart.

Conclusion

As error correction can take excessive computational time, SparkEC provides a scalable solution for correcting large datasets. Due to its distributed implementation, SparkEC speed can increase with respect to the number of nodes in a cluster. Furthermore, the software is freely available under GPLv3 license and is compatible with different operating systems (Linux, Windows and macOS).
Duet: SNP-assisted structural variant calling and phasing using Oxford nanopore sequencing
Authors: Zhou Yekai , Leung Amy Wing-Sze , Ahmed Syed Shakeel , Lam Tak-Wah , Luo Ruibang
Published: November 2022

Background

Whole genome sequencing using the long-read Oxford Nanopore Technologies (ONT) MinION sequencer provides a cost-effective option for structural variant (SV) detection in clinical applications. Despite the advantage of using long reads, however, accurate SV calling and phasing are still challenging.

Results

We introduce Duet, an SV detection tool optimized for SV calling and phasing using ONT data. The tool uses novel features integrated from both SV signatures and single-nucleotide polymorphism signatures, which can accurately distinguish SV haplotype from a false signal. Duet was benchmarked against state-of-the-art tools on multiple ONT sequencing datasets of sequencing coverage ranging from 8× to 40×. At low sequencing coverage of 8×, Duet performs better than all other tools in SV calling, SV genotyping and SV phasing. When the sequencing coverage is higher (20× to 40×), the F1-score for SV phasing is further improved in comparison to the performance of other tools, while its performance of SV genotyping and SV calling remains higher than other tools.

Conclusion

Duet can perform accurate SV calling, SV genotyping and SV phasing using low-coverage ONT data, making it very useful for low-coverage genomes. It has great performance when scaled to high-coverage genomes, which is adaptable to various clinical applications. Duet is open source and is available at https://github.com/yekaizhou/duet.
Association between hepatic steatosis and fibrosis with measures of insulin sensitivity in patients with severe obesity and type 2 diabetes - a cross-sectional study
Authors: Seeberg Kathrine Aglen , Hofsø Dag , Borgeraas Heidi , Grimnes John Olav , Fatima Farhat , Seeberg Lars Thomas , Kvan Nils Petter , Svanevik Marius , Hertel Jens Kristoffer , Hjelmesæth Jøran
Published: November 2022

Background

Obesity, non-alcoholic fatty liver disease (NAFLD) and insulin resistance are three pathological conditions highly correlated, but this relationship is not fully elucidated. Hence, we aimed to assess the association of hepatic steatosis and fibrosis with different measures of insulin sensitivity in patients with severe obesity and type 2 diabetes mellitus (T2DM).

Methods

A cross-sectional study (Oseberg trial) including patients with T2DM referred for bariatric surgery at Vestfold Hospital Trust, Norway. Magnetic resonance imaging (MRI) and the enhanced liver fibrosis (ELF) test was used for estimation of liver fat fraction (LFF) and degree of fibrosis, respectively. Oral and intravenous glucose tolerance tests were applied for estimation of insulin sensitivity (HOMA2S, Matsuda ISI and MinMod SI).

Results

A total of 100 patients (mean [SD] age 47.5 [9.7] years, 65% women, BMI 42.0 [5.3] kg/m2 and 98% with metabolic syndrome) were included in the analyses. The mean (SD) LFF in the total population was 19.1 (11.5), and the mean (SD) ELF score was 8.46 (0.84), a value representing moderate fibrosis. LFF was inversely associated with HOMA2S and Matsuda ISI, and both measures were significantly higher in the no or low-grade steatosis group compared with the medium-to-high grade steatosis group (mean difference [95% CI] 5.9 [2.2-9.6]%, Cohen’s d = 0.75), and (0.7 [0.3-1.1], Cohen’s d = 0.80, respectively). There was no association between LFF, as a categorical or continuous variable, and MinMod SI. The proportions of patients with none to mild fibrosis, moderate fibrosis and severe fibrosis were 14, 78 and 6%, respectively, and there were no significant associations between level of fibrosis and measures of insulin sensitivity.

Conclusions

Patients with morbid obesity and T2DM demonstrated high levels of liver fat fraction, and we showed that hepatic steatosis, but not the degree of liver fibrosis, was associated with different measures of insulin sensitivity in patients with severe obesity and T2DM. Further, our results might indicate that the LFF is primarily associated with hepatic, and not peripheral insulin sensitivity. To improve the diagnosis of NAFLD and the prediction of its progression, more studies are needed to reveal the pathological mechanistic pathways involved in NAFLD and insulin sensitivity.

Trial registration

ClinicalTrials.gov: NCT01778738
Associations of five obesity indicators with cognitive performance in 30,697 Taiwan Biobank participants
Authors: Lin Wan-Yu
Published: November 2022

Background

Obesity adversely influences the central nervous system and cognitive functions. However, the relationship between various obesity indicators and cognitive performance remains controversial. It is unclear which obesity indicator is more relevant to cognitive impairment.

Methods

The Taiwan Biobank (TWB) administered the Chinese version of the Mini-Mental State Examination (MMSE) to 30,697 participants (12,094 males and 18,603 females) aged 60 to 70 years. A total of 3,454 (11.25%) individuals with MMSE < = 24 were classified as having poor cognitive performance. This cross-sectional study investigates the associations of five obesity indicators with cognitive performance. Five separate logistic regression models were fitted for males and another five for females. Covariates adjusted in all models included age, smoking status, drinking status, regular exercise, chronic disease status (diabetes, cardiovascular diseases, heart diseases, stroke, or Parkinson’s disease), depression status, blood pressure level, total cholesterol, fasting glucose, and educational attainment. The five obesity indicators included body mass index (BMI), body fat percentage (BFP), waist circumference (WC), hip circumference (HC), and waist-hip ratio (WHR).

Results

Abdominal obesity defined by WHR was significantly associated with poor cognitive performance. Male WHR > = 0.90 had a higher risk of poor cognitive performance than male WHR < 0.90 (odds ratio [OR] = 1.233;p = 0.007); female WHR > = 0.85 had an increased risk of poor cognitive performance compared with female WHR < 0.85 (OR = 1.221;p = 3.9E-4). HC and general obesity (defined by BMI and BFP) were not significantly associated with cognitive performance.

Conclusion

The results consistently agreed that preventing abdominal obesity is associated with better cognitive performance in both males and females.
Association between treatment failure and hospitalization after receipt of neutralizing monoclonal antibody treatment for COVID-19 outpatients
Authors: Douin David J. , Wogu Adane F. , Beaty Laurel E. , Carlson Nichole E. , Bennett Tellen D. , Aggarwal Neil R. , Mayer David A. , Ong Toan C. , Russell Seth , Steele Jeffrey , Peers Jennifer L. , Molina Kyle C. , Wynia Matthew K. , Ginde Adit A.
Published: November 2022

Background

Neutralizing monoclonal antibodies (mAbs) are highly effective in reducing hospitalization and mortality among early symptomatic COVID-19 patients in clinical trials and real-world data. While resistance to some mAbs has since emerged among new variants, characteristics associated with treatment failure of mAbs remain unknown.

Methods

This multicenter, observational cohort study included patients with COVID-19 who received mAb treatment between November 20, 2020, and December 9, 2021. We utilized electronic health records from a statewide health system plus state-level vaccine and mortality data. The primary outcome was mAb treatment failure, defined as hospitalization or death within 28 days of a positive SARS-CoV-2 test.

Results

COVID-19 mAb was administered to 7406 patients. Hospitalization within 28 days of positive SARS-CoV-2 test occurred in 258 (3.5%) of all patients who received mAb treatment. Ten patients (0.1%) died within 28 days, and all but one were hospitalized prior to death. Characteristics associated with treatment failure included having two or more comorbidities excluding obesity and immunocompromised status (adjusted odds ratio [OR] 3.71, 95% confidence interval [CI] 2.52–5.56), lack of SARS-CoV-2 vaccination (OR 2.73, 95% CI 2.01–3.77), non-Hispanic black race/ethnicity (OR 2.21, 95% CI 1.20–3.82), obesity (OR 1.79, 95% CI 1.36–2.34), one comorbidity (OR 1.68, 95% CI 1.11–2.57), age ≥ 65 years (OR 1.62, 95% CI 1.13–2.35), and male sex (OR 1.56, 95% CI 1.21–2.02). Immunocompromised status (none, mild, or moderate/severe), pandemic phase, and type of mAb received were not associated with treatment failure (all p > 0.05).

Conclusions

Comorbidities, lack of prior SARS-CoV-2 vaccination, non-Hispanic black race/ethnicity, obesity, age ≥ 65 years, and male sex are associated with treatment failure of mAbs.
Cyclosporine therapy could be considered for membranoproliferative glomerulonephritis with immunoglobulin A deposits: a case report
Authors: Hidaka Yuko , Tamura Hiroshi , Furuie Keishiro , Kuraoka Shohei , Nagata Hiroko , Nakazato Hitoshi
Published: November 2022

Background

Membranoproliferative glomerulonephritis (MPGN), a rare glomerulonephritis that causes nephrotic syndrome in children, is often difficult to treat. Typical immunofluorescence findings include strong C3 staining in a granular pattern along the glomerular capillary wall and negative IgA staining. IgA-dominant MPGN without hypocomplementemia has been reported. Herein, we report a rare case of MPGN with hypocomplementemia and predominant IgA subclass 2 deposits.

Case presentation

An 11-year-old girl showed proteinuria on a school urinalysis screening and presented with upper eyelid edema. The urinalysis showed elevated urinary protein levels and hematuria. Laboratory examinations revealed the following: serum albumin, 1.3 g/dL; serum creatinine, 0.54 mg/dL; and C3c, 67 mg/dL (normal range: 73–138 mg/dL). The physical and laboratory findings did not suggest autoimmune diseases. A renal biopsy was then performed. Specimen examination under a light microscope showed mesangial cell proliferation, increased mesangial matrix with lobulation, and some double contours of the glomerular basement membrane in almost all glomeruli, which are characteristic findings of MPGN. Immunofluorescent studies showed IgA deposits not only in the mesangial regions but also along the capillary walls, which were more strongly stained than C3. IgA subclass staining showed a stronger immunoreactivity for IgA2 than IgA1. Electron microscopic studies showed electron-dense deposits in the subendothelial, subepithelial, and paramesangial regions. Based on these findings, the patient was diagnosed with IgA-dominant MPGN. Accordingly, she was treated with three courses of methylprednisolone pulse therapy (MPT), followed by prednisolone, mizoribine, and lisinopril. Although hypocomplementemia improved after three courses of MPT, nephrotic-range proteinuria and hypoalbuminemia remained; therefore, two courses of MPT were additionally administered, and the immunosuppressant was changed from mizoribine to cyclosporine (CsA). Finally, the urinary protein level decreased, and a subsequent renal biopsy, two years later, showed improvement in the lesions.

Conclusions

We report an atypical case of MPGN with IgA2 dominant deposits along the glomerular capillary wall and in the mesangial region. The case was refractory to standard therapy but sensitive to CsA, which resulted in remission. Our findings suggest that CsA may be useful as an immunosuppressant to treat refractory MPGN.
Treatment of early borderline lesions in low immunological risk kidney transplant patients: a Spanish multicenter, randomized, controlled parallel-group study protocol: the TRAINING study
Authors: Hernández Domingo , Vázquez-Sánchez Teresa , Sola Eugenia , Lopez Veronica , Ruiz-Esteban Pedro , Caballero Abelardo , Salido Eduardo , Leon Myriam , Rodriguez Aurelio , Serra Nuria , Rodriguez Consuelo , Facundo Carme , Perello Manel , Silva Irene , Marrero-Miranda Domingo , Cidraque Ignacio , Moreso Francesc , Guirado Luis , Serón Daniel , Torres Armando
Published: November 2022

Background

Subclinical inflammation, including borderline lesions (BL), is very common (30–40%) after kidney transplantation (KT), even in low immunological risk patients, and can lead to interstitial fibrosis/tubular atrophy (IFTA) and worsening of renal function with graft loss. Few controlled studies have analyzed the therapeutic benefit of treating these BL on renal function and graft histology. Furthermore, these studies have only used bolus steroids, which may be insufficient to slow the progression of these lesions. Klotho, a transmembrane protein produced mainly in the kidney with antifibrotic properties, plays a crucial role in the senescence-inflammation binomial of kidney tissue. Systemic and local inflammation decrease renal tissue expression and soluble levels of α-klotho. It is therefore important to determine whether treatment of BL prevents a decrease in α-klotho levels, progression of IFTA, and loss of kidney function.

Methods

The TRAINING study will randomize 80 patients with low immunological risk who will receive their first KT. The aim of the study is to determine whether the treatment of early BL (3rd month post-KT) with polyclonal rabbit antithymocyte globulin (Grafalon®) (6 mg/kg/day) prevents or decreases the progression of IFTA and the worsening of graft function compared to conventional therapy after two years post-KT, as well as to analyze whether treatment of BL with Grafalon® can modify the expression and levels of klotho, as well as the pro-inflammatory cytokines that regulate its expression.

Discussion

This phase IV investigator-driven, randomized, placebo-controlled clinical trial will examine the efficacy and safety of Grafalon® treatment in low-immunological-risk KT patients with early BL.

Trial registration

clinicaltrials.gov: NCT04936282. Registered June 23, 2021, https://clinicaltrials.gov/ct2/show/NCT04936282?term=NCT04936282&draw=2&rank=1. Protocol Version 2 of 21 January 2022. Sponsor: Canary Isles Institute for Health Research Foundation, Canary Isles (FIISC). mgomez@fciisc.org.
Individual dynamic prediction and prognostic analysis for long-term allograft survival after kidney transplantation
Authors: Huang Baoyi , Huang Mingli , Zhang Chengfeng , Yu Zhiyin , Hou Yawen , Miao Yun , Chen Zheng
Published: November 2022

Background

Predicting allograft survival is vital for efficient transplant success. With dynamic changes in patient conditions, clinical indicators may change longitudinally, and doctors’ judgments may be highly variable. It is necessary to establish a dynamic model to precisely predict the individual risk/survival of new allografts.

Methods

The follow-up data of 407 patients were obtained from a renal allograft failure study. We introduced a landmarking-based dynamic Cox model that incorporated baseline values (age at transplantation, sex, weight) and longitudinal changes (glomerular filtration rate, proteinuria, hematocrit). Model performance was evaluated using Harrell’s C-index and the Brier score.

Results

Six predictors were included in our analysis. The Kaplan–Meier estimates of survival at baseline showed an overall 5-year survival rate of 87.2%. The dynamic Cox model showed the individual survival prediction with more accuracy at different time points (for the 5-year survival prediction, the C-index = 0.789 and Brier score = 0.065 for the average of all time points) than the static Cox model at baseline (C-index = 0.558, Brier score = 0.095). Longitudinal covariate prognostic analysis (with time-varying effects) was performed.

Conclusions

The dynamic Cox model can utilize clinical follow-up data, including longitudinal patient information. Dynamic prediction and prognostic analysis can be used to provide evidence and a reference to better guide clinical decision-making for applying early treatment to patients at high risk.
Increased volume of cerebral oedema is associated with risk of acute seizure activity and adverse neurological outcomes in encephalitis – regional and volumetric analysis in a multi-centre cohort
Authors: Alam Ali M. , Chen Jian P. K. , Wood Greta K. , Facer Bethany , Bhojak Maneesh , Das Kumar , Defres Sylviane , Marson Anthony , Granerod Julia , Brown David , Thomas Rhys H. , Keller Simon S. , Solomon Tom , Michael Benedict D.
Published: November 2022

Background

Seizures can occur unpredictably in patients with acute encephalitis syndrome (AES), and many suffer from poor long-term neurological sequelae. Establishing factors associated with acute seizures risk and poor outcomes could support clinical care. We aimed to conduct regional and volumetric analysis of cerebral oedema on magnetic resonance imaging (MRI) in patients with AES. We assessed the relationship of brain oedema with acute seizure activity and long-term neurological outcome.

Methods

In a multi-centre cohort study, adults and children presenting with an AES were recruited in the UK. The clinical and brain MRI data were retrospectively reviewed. The outcomes variables were inpatient acute seizure activity and neurological disability at six-months post-discharge. A poor outcome was defined as a Glasgow outcome score (GOS) of 1–3. We quantified regional brain oedema on MRI through stereological examination of T2-weighted images using established methodology by independent and blinded assessors. Clinical and neuroimaging variables were analysed by multivariate logistic regression to assess for correlation with acute seizure activity and outcome.

Results

The study cohort comprised 69 patients (mean age 31.8 years; 53.6% female), of whom 41 (59.4%) had acute seizures as inpatients. A higher Glasgow coma scale (GCS) score on admission was a negative predictor of seizures (OR 0.61 [0.46–0.83], p = 0.001). Even correcting for GCS on admission, the presence of cortical oedema was a significant risk factor for acute seizure activity (OR 5.48 [1.62–18.51], p = 0.006) and greater volume of cerebral oedema in these cortical structures increased the risk of acute seizures (OR 1.90 [1.12–3.21], p = 0.017). At six-month post-discharge, 21 (30.4%) had a poor neurological outcome. Herpes simplex virus encephalitis was associated with higher risk of poor outcomes in univariate analysis (OR 3.92 [1.08–14.20], p = 0.038). When controlling for aetiology, increased volume of cerebral oedema was an independent risk factor for adverse neurological outcome at 6 months (OR 1.73 [1.06–2.83], p = 0.027).

Conclusions

Both the presence and degree of cerebral oedema on MRIs of patients with AES may help identify patients at risk of acute seizure activity and subsequent long-term morbidity.
Exploring the utility and acceptability of Faecal immunochemical testing (FIT) as a novel intervention for the improvement of colorectal Cancer (CRC) surveillance in individuals with lynch syndrome (FIT for lynch study): a single-arm, prospective, multi-centre, non-randomised study
Authors: Lincoln Anne , Benton Sally , Piggott Carolyn , North Bernard V. , Rigney Jane , Young Caroline , Quirke Philip , Sasieni Peter , Monahan Kevin J.
Published: November 2022

Background

Lynch Syndrome (LS) is an inherited cancer predisposition syndrome defined by pathogenic variants in the mismatch repair (MMR) or EPCAM genes. In the United Kingdom, people with LS are advised to undergo biennial colonoscopy from as early as 25 until 75 years of age to mitigate a high lifetime colorectal cancer (CRC) risk, though the consideration of additional surveillance intervention(s) through the application of non-invasive diagnostic devices has yet to be longitudinally observed in LS patients. In this study, we will examine the role of annual faecal immunochemical testing (FIT) alongside biennial colonoscopy for CRC surveillance in people with LS.

Methods/design

In this single-arm, prospective, non-randomised study, 400 LS patients will be recruited across 11 National Health Service (NHS) Trusts throughout the United Kingdom. Study inclusion requires a LS diagnosis, between 25 and 73 years old, and a routine surveillance colonoscopy scheduled during the recruitment period. Eligible patients will receive a baseline OC-Sensor™ FIT kit ahead of their colonoscopy, and annually for 3 years thereafter. A pre-paid envelope addressed to the central lab will be included within all patient mailings for the return of FIT kits and relevant study documents. A questionnaire assessing attitudes and perception of FIT will also be included at baseline. All study samples received by the central lab will be assayed on an OC-Sensor™ PLEDIA Analyser. Patients with FIT results of ≥6 μg of Haemoglobin per gram of faeces (f-Hb) at Years 1 and/or 3 will be referred for colonoscopy via an urgent colonoscopy triage pathway.

16S rRNA gene V4 amplicon sequencing will be carried out on residual faecal DNA of eligible archived FIT samples to characterise the faecal microbiome.

Discussion

FIT may have clinical utility alongside colonoscopic surveillance in people with LS. We have designed a longitudinal study to examine the efficacy of FIT as a non-invasive modality. Potential limitations of this method will be assessed, including false negative or false positive FIT results related to specific morphological features of LS neoplasia or the presence of post-resection anastomotic inflammation. The potential for additional colonoscopies in a subset of participants may also impact on colonoscopic resources and patient acceptability.

Trial registration

Trial Registration: ISRCTN, ISRCTN15740250. Registered 13 July 2021.
Posterior microphthalmos with achievement of good visual acuity and disappearance of papillomacular retinal folds: a case report
Authors: Hanyu Takako , Ueki Satoshi , Hasegawa Yukari , Kiyokawa Megumi , Fukuchi Takeo
Published: November 2022

Background

Posterior microphthalmos (PM) is a rare condition with poor visual prognosis even after amblyopia treatment. We report a case of PM with achievement of good visual acuity and disappearance of papillomacular retinal folds (PFs) over a period of 7 years.

Case presentation

A girl aged 3 years and 5 months was referred to our hospital, after poor visual acuity was identified at a medical checkup for 3-year-olds. She had severe spherical hyperopia: + 17.25 D in the right eye (RE) and + 18 D in the left eye (LE). Her corrected visual acuity was 20/200 in the RE and 20/250 in the LE. PFs were observed in both eyes on optical coherence tomography (OCT), and the diagnosis of PM was made based on the normal corneal diameter and anterior chamber depth. During the course of the disease, a gradual decrease in the height of the PFs was observed on OCT. The corrected visual acuity at age 10 years was 20/20 in the RE and 20/25 in the LE.

Conclusions

The visual prognosis of PM is poor, and only one case with good visual acuity has been reported in the literature. The patient in the present case not only developed good visual acuity, but also showed improvement in macular morphology, which was not noted in previous reports. Early diagnosis of PM and early amblyopia treatment is important for the visual development in PM.
Distance to sports facilities and low frequency of exercise and obesity: a cross-sectional study
Authors: Raza Auriba , Pulakka Anna , Hanson Linda L Magnusson , Westerlund Hugo , Halonen Jaana I.
Published: November 2022

Background

Little research has investigated the associations between proximity to physical activity facilities and behavior-related health and the majority have focused on proximity from home address. We add to the literature by examining proximity of these facilities to work and home address and including a wide range of physical activity facilities. We assess the associations for proximity of physical activity facilities from home and work address with self-reported frequency of exercise and obesity.

Methods

Our analytical sample of 7358 participants was from the 2018 wave of the Swedish Longitudinal Occupational Survey of Health. We used logistic binomial regression adjusting for age, sex, education, civil status, individual socioeconomic status, neighborhood socioeconomic status, number of children under 12 years of age, work strain, and chronic disease.

Results

Longer distance from home to paid outdoor and paid indoor physical activity facilities was associated with low frequency of exercise (fully adjusted Relative Risk for both 1.01, 95% CI 1.01–1.02). Associations of any or free outdoor facility with low frequency of exercise were not robust. Findings also indicated associations between long distance from workplace to any and paid outdoor facility and low frequency of exercise. Results for obesity were in the similar direction, however, these were not statistically significant.

Conclusion

Increased distance of paid outdoor and paid indoor physical activity facilities from home and of paid outdoor facilities from work was associated with low frequency of exercise. Longitudinal and larger studies are needed to confirm our findings, particularly regarding obesity.
The effect of N-acetylcysteine in patients with non-cystic fibrosis bronchiectasis (NINCFB): study protocol for a multicentre, double-blind, randomised, placebo-controlled trial
Authors: Liao Yue , Wu Yanqiu , Zi Kai , Shen Yongchun , Wang Tao , Qin Jiangyue , Chen Lei , Chen Mei , Liu Lin , Li Weiming , Zhou Hui , Xiong Shuguan , Wen Fuqiang , Chen Jun
Published: November 2022

Background

N-acetylcysteine (NAC), which is specifically involved in airway mucus clearance and antioxidation, is recommended by the treatment guideline for non-cystic fibrosis bronchiectasis (NCFB). However, there is little clinical evidence of its long-term efficacy concerning quality of life (QoL) and exacerbation in patients with NCFB. In addition, the influences of NAC on airway bacterial colonization, chronic inflammation and oxidative stress in NCFB are also unclear.

Methods

NINCFB is a prospective, multicentre, double-blind, randomised, placebo-controlled trial that will recruit 119 patients with NCFB and randomly divide them into an NAC group (n = 79) and a control group (n = 40). Participants in the NAC group will receive 600 mg oral NAC twice daily for 52 weeks, while patients in the control group will receive 600 mg placebo twice daily for 52 weeks. The information at baseline will be collected once participants are enrolled. The primary endpoints are the changes in St George’s Respiratory Questionnaire scores and the number of exacerbations in 52 weeks. The secondary endpoints are the 16S rRNA of sputum and the levels of inflammatory factors and oxidative stressors in sputum and serum. Other data related to radiography, lung function tests, number of oral and/or intravenous antibiotic therapies and adverse events (AEs) will also be analysed. Further subgroup analysis distinguished by the severity of disease, severity of lung function, airway bacterial colonization and exacerbation frequency will be performed.

Discussion

The objective of this study is to determine the long-term efficacy of NAC on QoL and exacerbation of NCFB and to explore the effectiveness of NAC for antibiosis, anti-inflammation and antioxidation in NCFB. The study results will provide high-quality clinical proof for the revision and optimization of treatment guidelines and for expert consensus on NCFB treatment.

Trial registration

The trial was registered on the Chinese Clinical Trial Register at April 11, 2020 (chictr.org.cn, ChiCTR2000031817).
A novel likely pathogenic variant in the FBXO32 gene associated with dilated cardiomyopathy according to whole‑exome sequencing
Authors: Ghasemi Serwa , Mahdavi Mohammad , Maleki Majid , Salahshourifar Iman , Kalayinia Samira
Published: November 2022

Background

Familial dilated cardiomyopathy (DCM) is a genetic heart disorder characterized by progressive heart failure and sudden cardiac death. Over 250 genes have been reported in association with DCM; nonetheless, the genetic cause of most DCM patients has been unknown. The goal of the present study was to determine the genetic etiology of familial DCM in an Iranian family.

Methods

Whole-exome sequencing was performed to identify the underlying variants in an Iranian consanguineous family with DCM. The presence of the candidate variant was confirmed and screened in available relatives by PCR and Sanger sequencing. The pathogenic effect of the candidate variant was assessed by bioinformatics analysis, homology modeling, and docking.

Results

One novel likely pathogenic deletion, c.884_886del: p.Lys295del, in F-box only protein 32 (muscle-specific ubiquitin-E3 ligase protein; FBXO32) was identified. Based on bioinformatics and modeling analysis, c.884_886del was the most probable cause of DCM in the studied family.

Conclusions

Our findings indicate that variants in FBXO32 play a role in recessive DCM. Variants in FBXO32 may disturb the degradation of target proteins in the ubiquitin–proteasome system and lead to severe DCM. We suggest considering this gene variants in patients with recessively inherited DCM.
High-density lipoprotein cholesterol efflux capacity in patients with obstructive sleep apnea and its relation with disease severity
Authors: Fadaei Reza , Mohassel Azadi Samaneh , Rhéaume Eric , Khazaie Habibolah
Published: November 2022

Background

Obstructive sleep apnea (OSA) is linked to an accelerated risk of cardiovascular disease (CVD). Some key CVD risk factors are present in patients suffering from OSA such as hypertension, inflammation, oxidative stress, and dyslipidemia. High-density lipoprotein (HDL) cholesterol efflux capacity (CEC) is proposed as a reliable biomarker of HDL function and the present study aimed to quantify this biomarker in patients with OSA.

Methods

ATP binding cassette subfamily A member 1 (ABCA1), non-ABCA1, and total CEC were determined in 69 polysomnographic-confirmed OSA patients and 23 controls. Moreover, paraoxonase (PON) activities, high-sensitivity C-reactive protein (hsCRP), apolipoprotein B (apo B), and apolipoprotein A-I (apo A-I) circulating levels were quantified in the studied population.

Results: All CEC measures were reduced in the OSA group compared to the control group. Strikingly, ABCA1 CEC was diminished in severe OSA in comparison with mild OSA. Furthermore, PON activities and apo A-I showed lower levels, while hsCRP and apo B were elevated in OSA patients compared to controls. Moreover, ABCA1 CEC showed an inverse association with hsCRP and a positive association with apo A-I, while non-ABCA1 CEC presented an association with HDL-C.

Conclusion

These results suggest the presence of an impaired HDL function in OSA. In particular, ABCA1 CEC was associated with disease severity and inflammation which could be a factor increasing the risk of CVD.
Comprehensive transcriptional variability analysis reveals gene networks regulating seed oil content of Brassica napus
Authors: Tan Zengdong , Peng Yan , Xiong Yao , Xiong Feng , Zhang Yuting , Guo Ning , Tu Zhuo , Zong Zhanxiang , Wu Xiaokun , Ye Jiang , Xia Chunjiao , Zhu Tao , Liu Yinmeng , Lou Hongxiang , Liu Dongxu , Lu Shaoping , Yao Xuan , Liu Kede , Snowdon Rod J. , Golicz Agnieszka A. , Xie Weibo , Guo Liang , Zhao Hu
Published: November 2022

Background

Regulation of gene expression plays an essential role in controlling the phenotypes of plants. Brassica napus (B. napus) is an important source for the vegetable oil in the world, and the seed oil content is an important trait of B. napus.

Results

We perform a comprehensive analysis of the transcriptional variability in the seeds of B. napus at two developmental stages, 20 and 40 days after flowering (DAF). We detect 53,759 and 53,550 independent expression quantitative trait loci (eQTLs) for 79,605 and 76,713 expressed genes at 20 and 40 DAF, respectively. Among them, the local eQTLs are mapped to the adjacent genes more frequently. The adjacent gene pairs are regulated by local eQTLs with the same open chromatin state and show a stronger mode of expression piggybacking. Inter-subgenomic analysis indicates that there is a feedback regulation for the homoeologous gene pairs to maintain partial expression dosage. We also identify 141 eQTL hotspots and find that hotspot87-88 co-localizes with a QTL for the seed oil content. To further resolve the regulatory network of this eQTL hotspot, we construct the XGBoost model using 856 RNA-seq datasets and the Basenji model using 59 ATAC-seq datasets. Using these two models, we predict the mechanisms affecting the seed oil content regulated by hotspot87-88 and experimentally validate that the transcription factors, NAC13 and SCL31, positively regulate the seed oil content.

Conclusions

We comprehensively characterize the gene regulatory features in the seeds of B. napus and reveal the gene networks regulating the seed oil content of B. napus.
Screen-printed sensors for efficient potentiometric analysis of tolperisone hydrochloride in presence of its co-formulated drugs
Authors: Rizk Mohamed , Hussein Emad M. , Toubar Safaa , Ramzy Emad , Helmy Marwa I.
Published: November 2022

Researchers seeking for green chemistry to help safeguard and boost the economy and the environment by discovering unique ways to decrease waste and find substitutes for dangerous chemicals. In this study, a green potentiometric ion-selective electrode (ISE) was developed for measurement of tolperisone HCl (TOLP) in bulk and Pharmaceutical dosage forms in presence of diclofenac sodium and paracetamol as co-formulated drugs. This paper presents the manufacture and characterization of a disposable potentiometric ion-selective strip with an enhanced detection limit for (TOLP) measurement in its tablet dosage form either alone or in presence of the co-formulated drugs. Numerous ion pairs (IPs), such as TOLP-tetraphenylborate (TOLP-TPB), TOLP-phosphotungstic acid (TOLP-PTA), and TOLP-ammonium Reinecke (TOLP- RKT) are tested in presence of different plasticizers. The optimal potentiometric response with a near Nernstian slope of 55.949 mV/decade was achieved within a linear concentration range of 5 $$\times$$
×
10–5 − 1 $$\times$$
×
10–2 M using (PTA) and ortho nitrophenyl octyl ether (o-NPOE) as a plasticizer. The effect of the nanoparticles on the membrane stability was studied using the graphene nanoplatelets which have an effective role in the enhancement of some constructed sensors stability. Finally, the developed technique is validated for the estimation of TOLP with high accuracy and precision.

Graphical Abstract