bluuebunny/crossref_metadata_2025 huggingface dataset:
Two novel truncating variants of the ASPM gene identified in a nonconsanguineous Chinese family associated with primary microcephaly
Authors: Xu Shuqin , Zhang Wenqian , Zhou Rui , Huang Hui , Chen Wei , Xiang Wenhao , Liu Limei , Song Jieping
Published: October 2021

Primary autosomal recessive microcephaly 5 (MCPH5) is a rare neurodevelopmental disorder with a relatively high incidence in regions where consanguineous marriage is widely practiced; So far, only a few MCPH5 cases have been reported from China. Here, we report clinical and molecular characteristics of two Chinese MCPH5 patients, a 24-year-old woman proband and her brother, a 19-year-old man, from a nonconsanguineous family. Main manifestations in the proband were small head circumference, premature closure of fontanelles, impaired concentration and moderate intellectual disability. The proband’s brother had similar symptoms, but he was hyperactive and had a more severe sloping forehead. Brain imaging revealed global reduction in brain size, especially in the frontal lobes bilaterally and anterior horns of lateral ventricles. Sequencing results revealed that both patients carried a novel nonsense variant p.Tyr2004* (c.6012_6013delTA) and a novel frameshift variant p.Arg2005Serfs*48 (c.6015_6016delGG) in the ASPM gene. These variants were interpreted to be pathogenic in the in-silico analysis. Our findings help to expand the mutation spectrum of ASPM and provide new opportunities for assisting the traditional clinical diagnosis on the cases with atypical characteristics.
Familial combined hyperlipidemia is a polygenic trait
Authors: Gill Praneet K. , Hegele Robert A.
Published: October 2021

Purpose of review

: Familial combined hyperlipidemia (FCH), defined by concurrently elevated plasma triglyceride (TG) and low-density lipoprotein (LDL) cholesterol, has long been investigated to characterize its genetic basis. Despite almost half a century of searching, a single gene cause for the phenotype has not yet been identified.

Recent findings

: Recent studies using next-generation genetic analytic methods confirm that FCH has a polygenic basis, with a clear large contribution from the accumulation of small-to-moderate effect common single nucleotide polymorphisms (SNPs) throughout the genome that is associated with raising TG, and probably also those raising LDL cholesterol. On the other hand, rare monogenic variants, such as those causing familial hypercholesterolemia, play a negligible role, if any. Genetic profiling suggests that patients with FCH and hypertriglyceridemia share a strong polygenic basis and show a similar profile of multiple TG-raising common SNPs.

: Recent progress in genomics has shown that most if not all of the genetic susceptibility to FCH is polygenic in nature. Future research should include larger cohort studies, with wider ancestral diversity, ancestry-specific polygenic scores, and investigation of epigenetic and lifestyle factors to help further elucidate the causative agents at play in cases where the genetic etiology remains to be defined.
Severe Burnout and Poor Mental Health Among Healthcare Workers 6 Months After COVID-19 Pandemic Declaration
Authors: Kim Son Chae , Sloan Christine , Chechel Laura , Redila Matt , Ferguson Jennifer
Published: October 2021

OBJECTIVES

The aim of this study was to examine the predictors associated with severe burnout and poor mental health among healthcare workers during the COVID-19 pandemic as a learning opportunity for future emergent situations.

BACKGROUND

Modifiable predictors of mental health need to be further examined and quantified to prioritize human resource support in organizations as healthcare workers confront stressful situations.

METHODS

A cross-sectional survey was conducted among 271 healthcare workers from September 8 to October 10, 2020.

RESULTS

Approximately one-third reported severe burnout, as well as moderate/severe anxiety and depression. Feeling protected working with COVID-19 patients, high family functioning, and spirituality were associated with 2- to 4-fold lower odds of severe burnout. Satisfaction with the organization's communications predicted 2-fold lower odds of anxiety, whereas high resilience was associated with almost 4-fold lower odds of stress and depression.

CONCLUSIONS

Healthcare organizations may consider adopting programs to foster resilience, family and spiritual support, and effective communication strategies to reduce burnout and poor mental health among healthcare workers during pandemics and other situations of high stress.
Antiretroviral therapy for HIV and intrahepatic hepatitis C virus replication
Authors: Quinn Jeffrey R. , Goyal Ashish , Ribeiro Ruy M. , Massaccesi Guido , Bailey Justin R. , Thomas David L. , Balagopal Ashwin
Published: October 2021

Objective:

HIV alters host responses to hepatitis C virus (HCV). However, the impact of antiretroviral therapy (ART) on HCV is rarely understood in relevant tissues and never before within individual hepatocytes.

Design:

HIV and HCV kinetics were studied before and after ART initiation among 19 HIV/HCV co-infected persons. From five persons with the largest decline in plasma HCV RNA, liver tissues collected before and during ART, when plasma HIV RNA was undetectable, were studied.

Methods:

We used single-cell laser capture microdissection and quantitative PCR to assess intrahepatic HCV. Immunohistochemistry was performed to characterize intrahepatic immune cell populations.

Results:

Plasma HCV RNA declined by 0.81 (0.52–1.60) log10 IU/ml from a median (range) 7.26 (6.05–7.29) log10 IU/ml and correlated with proportions of HCV-infected hepatocytes (r = 0.89, P = 2 × 10−5), which declined from median (range) of 37% (6–49%) to 23% (0.5–52%) after plasma HIV clearance. Median (range) HCV RNA abundance within cells was unchanged in four of five participants. Liver T-cell abundance unexpectedly decreased, whereas natural killer (NK) and NK T-cell infiltration increased, correlating with changes in proportions of HCV-infected hepatocytes (r = −0.82 and r = −0.73, respectively). Hepatocyte expression of HLA-E, an NK cell restriction marker, correlated with proportions of HCV-infected hepatocytes (r = 0.79).

Conclusion:

These are the first data to show that ART control of HIV reduces the intrahepatic burden of HCV. Furthermore, our data suggest that HIV affects the pathogenesis of HCV infection by an NK/NK T-cell-mediated mechanism that may involve HLA-E and can be rescued, at least in part, by ART.
Randomized, Blinded, Placebo-Controlled Trial of De Simone Formulation Probiotic During HIV-Associated Suboptimal CD4+ T Cell Recovery
Authors: Rousseau Rodney K. , Walmsley Sharon L. , Lee Terry , Rosenes Ron , Reinhard Robert J. , Malazogu Fat , Benko Erika , Huibner Sanja , Kovacs Colin M. , Singer Joel , Kim Connie J. , Kaul Rupert
Published: October 2021

Objective:

To assess whether probiotic supplementation may reduce disease-linked systemic immune activation in people living with HIV with the immunologic nonresponder phenotype.

Design:

Phase 2b, randomized, double-blind, placebo-controlled pilot trial.

Methods:

HIV-positive individuals with blood CD4+ T-cell counts <350/mm3 despite viral suppression were randomized to 2:1 to receive De Simone Formulation Probiotic (DSFP; “Visbiome” commercially) or placebo for 48 weeks; target enrollment was 36 patients. The primary endpoint was the change in blood CD8+ T-cell coexpression of human leukocyte antigen-DR isotype and CD38 (“CD8 activation”). Secondary endpoints included biomarkers of inflammation, immune reconstitution, bacterial translocation, and gut permeability. Adjusted linear regression and linear mixed regression methods evaluated the differences between study arms from baseline to week 48. Study monitoring was performed by the CIHR Canadian HIV Trials Network Data Safety Monitoring Committee.

Results:

Nineteen patients received DSFP, whereas 10 received placebo. One probiotic arm patient withdrew early. Blood CD8 activation increased 0.82 percentage points (pp) in the probiotic arm (95% confidence interval: −1.23 to 2.87;) and decreased by 2.06 pp in the placebo arm (−4.81 to 0.70; between arms P = 0.097). CD4+ T-cell activation (%HLA-DR+) decreased in the placebo arm [−3.79 pp (−7.32 to −0.26)] but increased in the probiotic arm [1.64 (−0.98 to 4.26); between arms P = 0.018]. No differences were observed in plasma or urine biomarkers of inflammation or microbial translocation.

Conclusions:

Blood immune activation markers in immunologic nonresponder individuals on effective antiretroviral treatment were not reduced by supplementation with DSFP; CD4+ T-cell activation may have been increased.
Prostate-Specific Membrane Antigen Radioguided Surgery for Salvage Pelvic Lymph Node Dissection in a Man With Prostate Cancer
Authors: Erfani Soheila , Sadeghi Ramin , Aghaee Atena , Ghorbani HamidReza , Roshanravan Vahid
Published: October 2021

A 75-year-old man with evidence of recurrent prostate cancer on 68Ga–prostate-specific membrane antigen (PSMA) PET/CT after radical prostatectomy was referred to our department for 99mTc-PSMA radioguided surgery. Intraoperatively, lymph nodes with high count rates were localized using a handheld gamma probe. High-count specimens were resected from the exact locations as reported by 68Ga-PSMA PET/CT. The total prostate-specific antigen value decreased 6 weeks after surgery. Our case shows the feasibility of radioguided surgery with 99mTc-PSMA for salvage lymphadenectomy in prostate cancer.
Treatment of Syndromic Craniosynostosis by Anterior and Posterior Vault Distraction Osteogenesis (A-PVDO)
Authors: Shen Weimin , Cui Jie , Chen Jianbing , Yi Ji , Kong Liangliang , Sun Buhao
Published: October 2021

Objective:

To explore the feasibility and therapeutic effect of anterior and posterior vault distraction osteogenesis (A-PVDO) in the treatment of infantile syndromic craniosynostosis.

Methods:

Between January 2017 and December 2019, 7 children with syndromic craniosynostosis underwent osteotomy with Piezo-surgery at our hospital. The first step was to harvest the frontal bone flap and the orbitofrontal bone flap. The second step was to separate the scalp and expose the posterior occipital. Osteotomy was performed on the occipital tubercle. Thereafter, 2 distractors were horizontally installed on the upper edge of the anterior cranial orbit, 2 distractors of 3 cm were installed on the posterior cranial bone. Meanwhile, lambdoidal sutures were fixed by titanium plates. Bone distraction was initiated on postoperative day 5 at the rate of 0.4 to 0.6 mm/day, twice per-day, for a total of 10 to 15 days. After 6 months, the distractors and the titanium plates were removed by secondary surgery.

Results:

The intracranial volume and posterior cranial morphology were recorded during the follow-up of 6 to 14 months (average = 12 months). The posterior craniums of 7 cases with lambdoidal sutures fixation were completely extended. The anterior cranial morphology was normal. All the cranial deformities were significantly improved. There were no severe complications, such as death, cranial necrosis, and intracranial infection.

Conclusions:

A-PVDO is an ideal method for the treatment of severe syndromic craniosynostosis, which can achieve more natural appearance than anterior vault distraction osteogenesis or posterior vault distraction osteogenesis. Moreover, A-PVDO causes no severe complications and is suitable for the treatment of severe syndromic craniosynostosis.
Midface Growth Potential in Unoperated Clefts: A Systematic Review and Meta-Analysis
Authors: Wlodarczyk Jordan R. , Munabi Naikhoba C.O. , Wolfswinkel Erik , Nagengast Eric , Higuch Emma C. , Turk Marvee , Urata Mark M. , Hammoudeh Jeffrey A. , Yao Caroline , Magee William
Published: October 2021

Competing hypotheses for the development of midface hypoplasia in patients with cleft lip and palate include both theories of an intrinsic restricted growth potential of the midface and extrinsic surgical disruption of maxillary growth centers and scar growth restriction secondary to palatoplasty. The following meta-analysis aims to better understand the intrinsic growth potential of the midface in a patient with cleft lip and palate unaffected by surgical correction. A systematic review of studies reporting cephalometric measurements in patients with unoperated and operated unilateral cleft lip and palate (UCLP), bilateral cleft lip and palate (BCLP), and isolated cleft palate (iCP) abstracted SNA and ANB angles, age at cephalometric analysis, syndromic diagnosis, and patient demographics. Age and Region-matched controls without cleft palate were used for comparison. SNA angle for unoperated UCLP (84.5 ± 4.0°), BCLP (85.3 ± 2.8°), and ICP (79.2 ± 4.2°) were statistically different than controls (82.4 ± 3.5°), (all P ≤ 0.001). SNA angles for operated UCLP (76.2 ± 4.2°), BCLP (79.8 ± 3.6°), and ICP (79.0 ± 4.3°) groups were statistically smaller than controls (all P ≤ 0.001). SNA angle in unoperated ICP (n = 143) was equivalent to operated ICP patients (79.2 ± 4.2° versus 79.0 ± 4.3° P = 0.78). No unoperated group mean SNA met criteria for midface hypoplasia (SNA < 80). Unoperated UCLP/BLCP exhibit a more robust growth potential of the maxilla, whereas operated patients demonstrate stunted growth compared to normal phenotype. Unoperated ICP demonstrates restricted growth in both operated and unoperated patients. As such, patients with UCLP/BCLP differ from patients with ICP and the factors affecting midface growth may differ.

Level of Evidence: IV
Massive Exophytic Brown's Tumor of the Bilateral Maxilla with Mandibular Involvement
Authors: Pham Matthew , Bhatt Poolak , Purvey Timothy A.
Published: October 2021

Brown's tumor is a benign bone lesion that occurs in the setting of hyperparathyroidism and can affect the facial skeleton. It often presents as a single lesion and is usually less than 3 centimeters. To our knowledge, no cases have been reported to have bilateral involvement of the maxilla and mandible with the largest dimension measuring over 7 centimeters. This report describes such a case and provides a review of the literature.
An atlas of associations between polygenic risk scores from across the human phenome and circulating metabolic biomarkers
Authors: Fang Si , Holmes Michael V , Gaunt Tom R , Smith George Davey , Richardson Tom G
Published: October 2021

Polygenic risk scores (PRS) are becoming an increasingly popular approach to predict complex disease risk, although they also hold the potential to develop insight into the molecular profiles of patients with an elevated genetic predisposition to disease. In this study, we have constructed an atlas of associations between 129 different PRS and 249 circulating metabolites in up to 83,004 participants from the UK Biobank study. As an exemplar to demonstrate the value of this atlas we conducted a hypothesis-free evaluation of all associations with glycoprotein acetyls (GlycA), an inflammatory biomarker. Using bi-directional Mendelian randomization, we find that the associations highlighted likely reflect the effect of risk factors, such as body mass index (Beta=0.16 per standard deviation change in GlycA, 95% CI=0.11 to 0.21, P=9.9×10−10) or liability towards smoking cigarettes (Beta=0.28, 95% CI=0.20 to 0.35, P=2.4×10−14), on systemic inflammation as opposed to the converse direction of effect. Furthermore, we repeated all analyses in our atlas within age strata to investigate potential sources of collider bias, such as medication usage. This was exemplified by comparing associations between lipoprotein lipid profiles and the coronary artery disease PRS in the youngest and oldest age strata, which had differing proportions of individuals undergoing statin therapy. All results can be visualised athttp://mrcieu.mrsoftware.org/metabolites_PRS_atlas.
Safety and Effectiveness of COVID-19 SPUTNIK V Vaccine in Dialysis Patients
Authors: Rosa-Diez Guillermo , Papaginovic Leiva María Marina , Lombi Fernando , Crucelegui María Soledad , Martínez Ricardo Dulio , Trimarchi Hernán , Schiavelli Rubén , Grizzo Mercedes , Raño Miguel , Heguilén Ricardo M. , Jones Rocío Anahí , Paganti Luciana Gonzalez , Ferrrari Matías , Zingoni Dra. Paula , Kjohede Victoria , Geffner Jorge Raúl , Ferrante Daniel , de Quirós Fernán González Bernaldo , Pagotto Vanina
Published: October 2021

Given the vulnerability of people with chronic kidney disease to COVID-19, nephrology societies have issued statements calling for prioritization of these patients for vaccination. It is not yet known whether COVID-19 vaccines confer the same high level of protection in patients with kidney disease. The aims of this study were to evaluate the safety measured by the events supposedly attributed to vaccines and the effectiveness evaluated by the presence of antibodies in dialysis patients immunized with the COVID-19 Sputnik V vaccine.

Methods

multicenter, observational and analytical study of a prospective cohort of hemodialysis patients in the Autonomous City of Buenos Aires with a vaccination plan. Patients older than 18 years on dialysis who received both components of the COVID-19 vaccine were included.

Results

491 patients included in the safety analysis. ESAVI with either the first or second component was detected in 186 (37.9% 95% CI 33.6%-42.34%). The effectiveness analysis measures of antibodies against SARS-Cov-2 were performed in 102 patients, 98% had positive IgG against SARS-Cov-2 antibodies 21 days after the second component .In patients with COVID-19 prior to vaccination, antibodies at day 21 after the first component reached almost the highest levels compared to those patients who did not have COVID-19, and the rise between the last measures was lower than patients without COVID-19.

Conclusion

Dialysis patients constitute a vulnerable population for SARS-Cov-2 infection, beyond the recommendations that were implemented by dialysis units, full vaccination is a priority and necessary. The Sputnik V vaccine has been shown to be safe and effective in this patient population.
Provider preferences for delivery of HIV care coordination services: results from a discrete choice experiment
Authors: Zimba Rebecca , Fong Chunki , Conte Madellena , Baim-Lance Abigail , Robertson McKaylee , Carmona Jennifer , Gambone Gina , Nash Denis , Irvine Mary
Published: October 2021

Introduction

The PROMISE study was launched in 2018 to assess and document the implementation of changes to an existing HIV Care Coordination Program (CCP) designed to address persistent disparities in care and treatment engagement among persons with HIV in New York City. We evaluated provider endorsement of features of the CCP to identify opportunities for improvement.

Methods

We used a discrete choice experiment (DCE) to measure provider endorsement of four CCP attributes, including: a) how CCP helps with medication adherence, b) how CCP helps with primary care appointments, c) how CCP helps with issues other than primary care, and d) where CCP visits take place (visit location). Each attribute had three to four levels. Our primary outcomes were relative importance and part-worth utilities, measures of preference for the levels of the four CCP program attributes.

Results

Visit location (28.6%) had the highest relative importance, followed by how staff help with ART adherence (24.3%), how staff help with issues other than primary care (24.2%), and how staff help with primary care appointments (22.9%). Within each of the above attributes, respectively, the levels with the highest part-worth utilities were home visits 60 minutes from the program or agency (19.9 utiles, 95% CI 10.7-29.0), directly observed therapy (26.1 utiles, 95% CI 19.1-33.1), help with non-HIV specialty medical care (26.5 utiles, 95% CI 21.5-31.6), and reminding clients about and accompanying them to primary care appointments (20.8 utiles, 95% CI 15.6-26.0).

Conclusions

Ongoing CCP refinements should account for how best to support and evaluate the intensive CCP components endorsed by providers in this study.
Analysis of Mechanistic Pathways in the Treatment of Non-Alcoholic Steatohepatitis. Evidence from a Bayesian Network Meta-Analysis
Authors: Muthiah Mark D. , Ng Cheng Han , Xiao Jieling , Chin Yip Han , Lim Grace , Lim Wen Hui , Tay Phoebe , Hao Tan Darren Jun , Yong Jie Ning , Pan Xin-Hui , Heng Koh Jeffery Wei , Chew Nicholas , Syn Nicholas , Tan Eunice , Huang Daniel Q. , Siddiqui Mohammad Shadab , Loomba Rohit , Sanyal Arun J. , Noureddin Mazen
Published: October 2021

Background and Aims

Non-alcoholic steatohepatitis (NASH) is the most common cause of liver disease contributing to significant disease burden worldwide. However, there is lack of comparison of efficacy between different NASH drug classes. We conducted a network meta-analysis evaluating drug classes through comparing histological outcomes and targets of drugs.

Approach & Results

Medline, EMBASE and CENTRAL were searched for articles evaluating NASH drugs in biopsy-proven NASH patients. Primary outcomes included NASH resolution without worsening of fibrosis, 2-point reduction in Non-alcoholic fatty liver disease Activity Score (NAS) without worsening of fibrosis and 1-point reduction in fibrosis. Treatments were classified into inflammation, energy, bile acid, and fibrosis modulators. The analysis was conducted with Bayesian network model and surface under the cumulative ranking curve (SUCRA) analysis.

From the 48 trials included, treatments modulating energy (Risk ratio (RR): 1.84, Credible intervals (Crl): 1.29 - 2.65) were the most likely to achieve NASH resolution followed by treatments modulating fibrosis (RR 1.68, Crl: 0.55 - 5.28), bile acids (RR: 1.34, Crl: 0.78 - 2.26) and inflammation (RR: 0.94, Crl: 0.59 - 1.46). Energy and bile acids modulation were effective in 2-point NAS reduction without worsening of fibrosis (RR: 1.60, Crl 1.13 - 2.30 and RR: 1.79, Crl 1.14 - 2.86) and 1-point fibrosis (RR: 1.27, Crl:1.05 - 1.52 and RR: 1.54, Crl: 1.20 - 1.97).

Conclusions

This network analysis demonstrates the relative superiority of drugs modulating energy pathways and bile acids in NASH treatment. This guides the development and selection of drugs for combination therapies.
Trends in the conduct and reporting of clinical prediction model development and validation: a systematic review
Authors: Yang Cynthia , Kors Jan A. , Ioannou Solomon , John Luis H. , Markus Aniek F. , Rekkas Alexandros , de Ridder Maria A.J. , Seinen Tom M. , Williams Ross D. , Rijnbeek Peter R.
Published: October 2021

Objectives

This systematic review aims to provide further insights into the conduct and reporting of clinical prediction model development and validation over time. We focus on assessing the reporting of information necessary to enable external validation by other investigators.

Materials and Methods

We searched Embase, Medline, Web-of-Science, Cochrane Library and Google Scholar to identify studies that developed one or more multivariable prognostic prediction models using electronic health record (EHR) data published in the period 2009-2019.

Results

We identified 422 studies that developed a total of 579 clinical prediction models using EHR data. We observed a steep increase over the years in the number of developed models. The percentage of models externally validated in the same paper remained at around 10%. Throughout 2009-2019, for both the target population and the outcome definitions, code lists were provided for less than 20% of the models. For about half of the models that were developed using regression analysis, the final model was not completely presented.

Discussion

Overall, we observed limited improvement over time in the conduct and reporting of clinical prediction model development and validation. In particular, the prediction problem definition was often not clearly reported, and the final model was often not completely presented.

Conclusion

Improvement in the reporting of information necessary to enable external validation by other investigators is still urgently needed to increase clinical adoption of developed models.
Genetically predicted levels of the human plasma proteome and risk of stroke: a Mendelian Randomization study
Authors: Chen Lingyan , Peters James E. , Prins Bram , Persyn Elodie , Traylor Matthew , Surendran Praveen , Karthikeyan Savita , Yonova-Doing Ekaterina , Di Angelantonio Emanuele , Roberts David J. , Watkins Nicholas A. , Ouwehand Willem H. , Danesh John , Lewis Cathryn M. , Bronson Paola G. , Markus Hugh S. , Burgess Stephen , Butterworth Adam S. , Howson Joanna M. M.
Published: October 2021

Proteins are the effector molecules of biology and are the target of most drugs. To identify proteins and related pathways that may play a causal role in stroke pathogenesis, we used Mendelian randomisation (MR). We tested potential causal effects of 308 plasma proteins (measured in 4,994 blood donors from the INTERVAL study) on stroke outcomes (derived from the MEGASTROKE GWAS) in a two-sample MR framework and assessed whether these associations could be mediated by cardiovascular risk factors. We extended the analysis to identify whether pharmacological targeting of these proteins might have potential adverse side-effects or beneficial effects for other conditions through Phenome-wide MR (Phe-MR) in UK Biobank.

MR showed an association between stroke and genetically predicted plasma levels of TFPI, IL6RA, MMP12, CD40, TMPRSS5 and CD6 (P≤1.62×10−4). We identified six risk factors (atrial fibrillation, body mass index, smoking, blood pressure, white matter hyperintensities and type 2 diabetes) that were associated with stroke (P≤0.0071) using MR. The association of TFPI, IL6RA and TMPRSS5 with stroke could be mediated by these risk factors, such as body mass index, white matter hyperintensity and atrial fibrillation. Thirty-six additional proteins were potentially causal for one or more of these risk factors. The Phe-MR suggested that targeting TFPI could have potential beneficial effects on other disorders of arteries and hyperlipidaemia in addition to stroke. Our results highlight novel causal pathways and potential therapeutic targets for stroke.
Unveiling Sex-based Differences in Parkinson’s Disease: A Comprehensive Meta-analysis of Transcriptomic Studies
Authors: López-Cerdán Adolfo , Andreu Zoraida , Hidalgo Marta R. , Grillo-Risco Rubén , Català-Senent José Francisco , Soler-Sáez Irene , Neva-Alejo Almudena , Gordillo Fernando , de la Iglesia-Vayá María , García-García Francisco
Published: October 2021

In recent decades, increasing longevity (among other factors) has fostered a rise in Parkinson’s disease (PD) incidence. Although not exhaustively studied in this devastating disease, the impact of sex represents a critical variable in PD as epidemiological and clinical features differ between males and females. To study sex bias in PD, we conducted a systematic review, tissue-specific meta-analyses of transcriptomic data from the frontal cortex (FC), striatum tissue (ST), and substantia nigra (SN), and a global meta-analysis of all 3 brain regions. We selected 7 PD studies that included sex information, analyzing 267 samples. The tissue-specific meta-analyses linked PD to the enhanced expression ofMED31in the female FC and the dysregulation of 237 genes in the SN. The global meta-analysis detected 15 genes with sex-differential patterns in PD, which participate in mitochondrial function, oxidative stress, neuronal degeneration, and cell death. Furthermore, functional analyses identified pathways, protein-protein interaction networks, and transcription factors that differed by sex. While male PD patients exhibited changes in oxidative stress based on metal ions, inflammation, and angiogenesis, female PD patients exhibited dysfunctions in mitochondrial and lysosomal activity, antigen processing and presentation functions, and glutamic and purine metabolism. Overall, we believe that our findings will provide new insight into the perspective of sex in PD, thereby underscoring the importance of including sex information in future PD studies.
Tsetse RNA Virome: Novel Iflavirus Genomes inGlossina morsitansand Other Tsetse Species
Authors: Manni M , Zdobnov EM
Published: October 2021

Tsetse flies (Glossinaspp.) are vectors of Human and Animal African trypanosomiasis. The tsetse microbiome has been extensively studied in the context of bacterial endosymbiont-host interactions, however, remarkably little is known about the tsetse virome with only one well-characterized DNA virus, the salivary gland hypertrophy virus (SGHV). Here we report the genomes of four iflaviruses identified in tsetse flies and their distribution in public RNA-seq libraries, mainly from laboratory colonies. Strikingly, the iflavirus identified inG. morsitans, provisionally named Glossina iflavirus 1 (GliflaV1), is present in all 136 RNA-seq libraries ofG. morsitansmaintained at different institutions, and displays a broad tissue tropism and high abundance, reaching up to 15% of library content. Its ubiquitous distribution and presence in the reproductive tissues, intrauterine larvae, and teneral flies suggest it is part of the initial core microbiota maternally transmitted to the progeny. None of theG. morsitanssamples harbor iflaviruses identified in the other three, more closely related, tsetse species which, conversely, do not harbor the iflavirus fromG. morsitans. Though apparently asymptomatic, these infections may influence tsetse host fitness, developmental or biological processes which might be relevant in the context of tsetse population control strategies, mass rearing, and paratransgenesis, and open up new opportunities to study the quadripartite system of interactions among the invertebrate host, the parasitic protozoan, and both viral and bacterial symbionts.
Jaboticaba peel extract as an antimicrobial agent: screening and stability analysis
Authors: Fleck Nataís , Sant’Anna Voltaire , Oliveira Wemerson de Castro , Brandelli Adriano , Fonseca Veras Flávio
Published: October 2021

Purpose

This study aimed to evaluate the antimicrobial activity of the aqueous extract from jaboticaba skin against important foodborne bacteria and fungi and its stability.

Design/methodology/approach

Jaboticaba skin aqueous extract (at ratio of 10 g L-1) was tested againstListeria monocytogenes,Staphylococcus aureus,Bacillus cereusandEscherichia coli. Stability of the anti-staphylococcal activity, total phenolics, monomeric anthocyanins, tannins, phenolic acid content were measured and statistically correlated.

Findings

The residue extract inhibited L.monocytogenes, S.aureus, B.cereus and E.coli growth but was not effective against fungi and was stable to the thermal treatments, remaining with its inhibitory activity against S.aureus. When stored for 14 days at 25 °C with an incidence of light, there was a reduction in the antibacterial activity and in the phenolic compounds. The change in pH slightly changed polyphenolic content profile, and the exposure to papain and bromelain did not affect the antimicrobial activity. Results showed strong correlation between anti-staphylococcal activity, the presence of polyphenols and anthocyanins, meanwhile moderate correlation with phenolic acids content in the extract.

Originality/value

Biopreservatives are a great trend in food microbiology. The present work shows deeper information about the utilization of jaboticaba skin as antimicrobial agent and its stability, which is not found in the current literature.
Revisiting the interconnection between governance mechanisms and firm performance: evidence from Vietnamese listed firms
Authors: Tran Cong Duc , Nguyen Tin Trung , Wang Jo-Yu
Published: October 2021

Purpose

Corporate governance plays a critical role in solving agency problems. However, previous findings on how governance mechanisms lead to high firm performance are inconclusive. Additionally, this relationship has not been well addressed in the context of transitional countries where governance systems and mechanisms are weak, leaving a gap for research. Hence, this study aims to shed light on the effects of four key governance components, namely, ownership concentration, chief executive officer duality, board size and gender diversity, on firm performance.

Design/methodology/approach

This study reports on the econometric panel data analysis and fuzzy-set qualitative comparative analysis (fsQCA) of 1,424 firm-year observations from listed companies in Vietnam covering the period of 2010–2017.

Findings

The econometric panel data analysis confirmed the net effects of single solitary governance components. FsQCA revealed equifinal configurations of components that explain high firm market- and accounting-based performance.

Practical implications

These findings are relevant for firms in transitional and emerging markets, aiming to adopt the most suitable internal mechanisms to pursue their performance objectives and for regulators interested in enhancing the advantages of the capital market.

Originality/value

This study provides empirical evidence that firm performance can be improved when the appropriate corporate governance mechanisms are selected. As there are equifinal paths leading to the desired outcome of high performance, firms from different industrial and national contexts should mindfully apply any uniform corporate governance code.
Policies, instrumentalities, compliance and control: combatting money laundering in Bangladesh
Authors: Zafarullah Habib , Haque Halima
Published: October 2021

Purpose

Money laundering (ML) has become a global threat in recent years, impacting both developed and poor countries. Developing an efficient anti-money laundering (AML) regime is a difficult and time-consuming process owing to the ever-changing spectrum of methods used, weaknesses in control mechanisms, intricacies of laws and regulations, organizational malfunction and goal displacement. In Bangladesh, surge of illegal money, rising money heists and egregious capital outflows have posed a governance problem. The purpose of this study is to investigate the dimensions of ML and examine the structure and performance of the AML regime.

Design/methodology/approach

This study adopts a qualitative method, based on a thorough review of the conceptual and empirical literature on ML, content analysis of a range of publications, a scan of newspaper articles and digital resources and responses/comments of current and retired government employees in Bangladesh. The evaluation is informed by the recommendations of the Financial Action Task Force and supported by the mutual evaluation reports of the AGroup on Money Laundering.

Findings

Bangladesh, like most of South Asia, is highly vulnerable to ML and is hard-pressed to fully comply with global standards for control. Weak institutions, bureaucratic pathology, lack of transparency and accountability, high levels of corruption, an ambiguous regulatory environment, unregulated financial operations, a disordered banking sector, conflicting interests, criminal exploitation, poor oversight and reporting, flawed risk assessment and weak government performance have affected the performance of the AML system.

Originality/value

This paper looks at the problem of ML from a holistic perspective covering different dimensions such as black money whitening, illegal funds movements, informal money transfer systems, use of offshore refuge for hiding money and so on and the state’s responses to the syndrome. The evaluation will be of particular relevance to policymakers, anti-corruption and law enforcement agencies, the financial intelligence operators and public prosecutors dealing with criminal justice.
Microbial survival and growth on non‐corrodible conductive materials
Authors: Bird Lina J. , Tender Leonard M. , Eddie Brian , Oh Eunkeu , Phillips Daniel A. , Glaven Sarah M.
Published: October 2021

Biofilms growing aerobically on conductive substrates are often correlated with a positive, sustained shift in their redox potential. This phenomenon has a beneficial impact on microbial fuel cells by increasing their overall power output but can be detrimental when occurring on stainless steel by enhancing corrosion. The biological mechanism behind this potential shift is unresolved and a metabolic benefit to cells has not been demonstrated. Here, biofilms containing the electroautotroph ‘Candidatus Tenderia electrophaga’ catalysed a shift in the open circuit potential of graphite and indium tin oxide electrodes by >100 mV. Biofilms on open circuit electrodes had increased biomass and a significantly higher proportion of ‘Ca. Tenderia electrophaga’ compared to those on plain glass. Addition of metabolic inhibitors showed that living cells were required to maintain the more positive potential. We propose a model to describe these observations, in which ‘Ca. Tenderia electrophaga’ drives the shift in open circuit potential through electron uptake for oxygen reduction and CO2 fixation. We further propose that the electrode is continuously recharged by oxidation of trace redox‐active molecules in the medium at the more positive potential. A similar phenomenon is possible on natural conductive substrates in the environment.
Public attitudes to a wealth tax: the importance of ‘capacity to pay’
Authors: Rowlingson Karen , Sood Amrita , Tu Trinh
Published: October 2021

In this paper, we present findings from the first ever study, to our knowledge, to focus in detail on public attitudes to an annual wealth tax. We start with a brief review of relevant recent studies before outlining the mixed methods used, which involved a nationally representative survey of 2,243 members of the general public and four focus groups conducted during the summer of 2020. The study aimed to measure, explore and explain the overall levels of support for a wealth tax compared with other taxes, the arguments for and against a wealth tax, and opinions on the particular design of such a tax. Key findings include high levels of public support for a wealth tax compared with other taxes, and support for the base of the tax to include financial investments and property wealth (after excluding the main home). The most popular rate/threshold combination is for the tax to be levied at a rate of at least 1 per cent over £500,000. Support for the tax appears to be driven by a combination of rational self‐interest and beliefs about fairness but, in particular, the public are keen for the tax to be focused on those with capacity to contribute the most.
Behavioural responses to a wealth tax
Authors: Advani Arun , Tarrant Hannah
Published: October 2021

In this paper, we review the existing empirical evidence on how individuals respond to the incentives created by a net wealth tax. Variation in the overall magnitude of behavioural responses is substantial: estimates of the elasticity of taxable wealth vary by a factor of 800. We explore three key reasons for this variation: tax design, context and methodology. We then discuss what is known about the importance of individual margins of response and how these interact with policy choices. Finally, we use our analysis to systematically narrow down and reconcile the range of elasticity estimates. We argue that a well‐designed wealth tax would reduce the tax base by 7–17 per cent if levied at a tax rate of 1 per cent.
Who should pay a wealth tax? Some design issues
Authors: Chamberlain Emma
Published: October 2021

Any wealth tax design needs to resolve the question of who should pay it it How wide should the net be cast? Setting high or low exempt thresholds affects avoidance behaviour and may influence whether one should tax by reference to the household (and if so how that should be defined) or simply on each individual who owns wealth over a certain threshold. Typically, wealth taxes in other countries have not been imposed on non‐residents except in relation to real property but questions remain over whether any exempt period should be given to new arrivals, not least for administrative convenience. A one‐off wealth tax would require a different design in a number of respects from an annual wealth tax. For example, a one off tax t would need to be designed to catch those who have recently left the UK and contain modifications for recent arrivals. Trusts, foundations and similar vehicles pose particular problems in the design of a wealth tax and the author suggests some possible solutions and connecting factors that could be considered.
Ways of taxing wealth: alternatives and interactions
Authors: Summers Andy
Published: October 2021

In this paper, I examine the role of a wealth tax in the context of the UK's existing taxes on wealth. First, I discuss several ways in which the UK could be said to tax wealth already, and I set out two possible directions for reforming these taxes, highlighting policies that are merited under either approach. Second, I consider whether and under what circumstances a broad‐based tax on the ownership of wealth – a ‘wealth tax’ – could be justified instead of or in addition to these reforms. Third, I address how a wealth tax should interact with other taxes, focusing on concerns regarding ‘double taxation’ and (conversely) proposals for an alternative minimum tax based on wealth. I conclude that there is a large degree of consensus amongst existing proposals to reform our current taxes on wealth, and that most of these reforms would be required whether or not a wealth tax is introduced as well.
The economic arguments for and against a wealth tax
Authors: Adam Stuart , Miller Helen
Published: October 2021

This paper asks when a wealth tax would, in principle, be a desirable part of the tax system, setting aside the practicalities and politics that would be crucial in reality. The case for a one‐off wealth tax is simple. If it were unexpected and credibly one‐off – a major challenge in practice – this would be an efficient way to raise revenue and could be used to address existing wealth inequality. Whether such a tax is desirable hinges on whether it is considered fair, about which reasonable people will differ. Making the case for an annual wealth tax, which would affect future wealth accumulation as well as existing wealth, is less straightforward. It requires explaining why it is better to tax the same wealth every year – penalising those who save – rather than raising the same revenue by taxing all sources of wealth once when they are received (and/or when they are spent). Such a case can be made based on subtle arguments for why taxing wealth might help to ease the trade‐off between redistribution and work incentives; and a wealth tax might also be justified if holding on to wealth, rather than spending it, benefits the holder or harms others. These theoretical arguments probably justify some taxation of wealth in principle, though we have little basis for judging the appropriate level, so only part of the theoretical benefit could be attained. It is questionable whether the achievable benefits outweigh the costs of an imperfect wealth tax in practice.

There are strong reasons to radically reform how we currently tax the sources/uses of wealth; this includes reforming capital income taxes in order to properly tax high returns. An annual wealth tax would be a poor substitute for doing that. But to the extent that taxes remain imperfect and that responses to a wealth tax would not affect revenue from other taxes (such as on income, expenditure and bequests), there may be a benefit to adding a wealth tax in order to diversify sources of revenue and prevent any one tax getting too high – though that must be weighed against the extra administrative burdens of having another tax.
Actor–partner association of work–family conflict and parental depressive symptoms during COVID‐19 in China: Does coparenting matter?
Authors: Zou Shengqi , Wu Xinchun , Ren Yizhen , Wang Xinyi
Published: October 2021

Parental depressive symptoms and their related factors have not been widely examined during the COVID‐19 pandemic. Therefore, the current study examined the actor and partner associations of work–family conflict and parental depressive symptoms. Considering the new demands and challenges for families during the COVID‐19 pandemic, we further explored the moderation effect of coparenting. A cross‐sectional online survey with 985 paired fathers and mothers was conducted in Mainland China. In 11.6% of families, only mothers reported moderate to severe depressive symptoms; in 10.6% families, only fathers reported moderate to severe depressive symptoms; in 9.5% families, the mother and father reported mild to moderate depressive symptoms. Results of the actor–partner interdependence model showed that parental family‐to‐work conflict was negatively associated with their own depressive symptoms. The negative actor association of maternal family‐to‐work conflict and depressive symptoms was moderated by undermining coparenting. The partner effects of maternal family‐to‐work and work‐to‐family conflicts on paternal depressive symptoms were moderated by undermining coparenting. Moreover, supportive coparenting moderated the actor association of work‐to‐family conflict and the depressive symptoms of fathers. Results highlight the importance of family‐to‐work conflict and family function for parental depressive symptoms. These findings can help promote parental well‐being during the COVID‐19 pandemic.
Liver biopsy in the real world—reporting, expert concordance and correlation with a pragmatic clinical diagnosis
Authors: Kim Hannah P. , Idowu Michael O. , Mospan Andrea R. , Allmon Andrew G. , Roden Michael , Newsome Philip , Lok Anna S. , Thuluvath Paul J. , Taunk Jawahar , Fried Michael W. , Sanyal Arun J. , Barritt A. Sidney ,   TARGET‐NASH Investigators
Published: October 2021

Background

Patients with non‐alcoholic steatohepatitis (NASH) and fibrosis stage ≥2 comprise a target population for pharmacotherapy. Liver biopsy, the reference standard for identifying this population, requires complete and accurate assessment of steatohepatitis and fibrosis.

Aims

To investigate the completeness of real‐world NASH‐related pathology reports, assess concordance between site pathologists and central expert interpretation of the histologic elements of NASH, and determine concordance between biopsy‐diagnosed NASH and a pragmatic clinical definition of NASH.

Methods

Liver pathology reports from 222 patients across 38 TARGET‐NASH sites were analysed for documentation of the histologic features of NASH. Biopsy slides were over‐read by a blinded central expert pathologist. Concordance of histologic scores and interpretation was assessed. Histologic concordance with a clinical definition of NASH was determined. TARGET‐NASH clinically defined NASH: elevated ALT, hepatic steatosis on biopsy or imaging and ≥1 of the following: BMI ≥30 kg/m2, type 2 diabetes mellitus and dyslipidaemia.

Results

Documentation of steatosis, lobular inflammation, portal inflammation and ballooning were missing from 21%, 35%, 46% and 40% of reports, respectively. There was slight‐to‐fair concordance (weighted kappa 0.01‐0.35) between site and central pathologists for inflammatory features, and moderate concordance (weighted kappa 0.56‐0.57) for fibrosis staging. Clinical definition of NASH was 75%‐91% concordant (94%‐95% sensitive) with biopsy‐diagnosed NASH.

Conclusions

There is substantial variability in reporting and grading NASH and fibrosis staging in clinical practice. This heterogeneity may adversely impact patient assessment and translation of practice guidelines into reality. The TARGET‐NASH pragmatic clinical definition may serve as a valuable tool to accurately identify NASH patients in clinical practice.