bluuebunny/crossref_metadata_2025 huggingface dataset:
Pediatric Extracranial Germ Cell Tumors: Expression of microRNA
Authors: Saliyeva Symbat , Boranbayeva Riza , Konoplya Natalya , Bulegenova Minira , Blau Olga , Belousov Vyacheslav , Granica Joanna , Mukushkina Dina , Altynbayeva Gulmira
Published: June 2022

Background:

Germ cell tumors (GCTs) may occur from the neonatal period to late adulthood, characterized by extensive clinical and pathologic heterogeneity. MicroRNAs are a family of small noncoding RNAs that regulate a wide array of biological processes including carcinogenesis. MicroRNAs may be used for many purposes in clinical diagnostics. Numerous studies have proven the diagnostic value of microRNA371-373 and microRNA302/367 expression in malignant GCT. The diagnostic value of microRNA375 is disputable, because while its value is confirmed by some research data, there are still others denying it.

Methods:

The results of our own research on the relative expression of 10 microRNAs, including microRNA375, associated with GCT in the tumor tissues of 84 children and adolescents are presented.

Results:

In our research, overexpression of microRNA 371-373, 302/367 detected in the group of malignant GCT subtypes. Statistically significant expression of microRNA375 have been defined not only in the group of malignant GCT subtypes, but also in the group of immature teratomas. Among malignant GCTs, high expression of microRNA375 is specific for yolk sac tumors. In the group of seminomas, embryonic carcinomas, and mature teratomas expression of microRNA375 was observed imperceptible, even so the results were statistically insignificant.

Conclusion:

Expression of microRNA 371-373, 302/367 is representative of malignant GCT subtypes. Statistically significant and high expression of microRNA375 attributable for yolk sac tumors and immature teratomas.
Bilateral Gonadoblastoma in a 6-Year-old Girl With Frasier Syndrome: Need for Early Preventive Gonadectomy
Authors: Kollios Konstantinos , Karipiadou Aristea , Papagianni Maria , Traeger-Synodinos Joanne , Kosta Konstantina , Savvidou Parthena , Stabouli Stella , Roilides Emmanuel
Published: June 2022

Frasier syndrome (FS) is a rare condition, caused by splice-site mutations of intron 9 in the Wilms’ tumor suppressor gene 1 (WT1 gene). The WT1 protein is essential for urogenital development and patients with 46XY karyotype present with female (FS type 1) or male phenotype, gonadal dysgenesis, progressive glomerulopathy, and high risk of gonadoblastoma. We describe a female patient with an IVS9+4C>T donor splice-site mutation, who underwent a preventive gonadectomy at the age of 6 years due to imaging findings of dysplastic gonads. The biopsy revealed bilateral gonadoblastoma, emphasizing the need for early gonadectomy in 46XY FS patients.
WHY QUESTIONNAIRE SCORES ARE NOT MEASURES: A QUESTION-RAISING ARTICLE
Authors: Tesio Luigi , Scarano Stefano , Hassan Samah , Kumbhare Dinesh , Caronni Antonio
Published: June 2022

Any person is provided by characteristics that can be neither located in body parts nor directly observed (so-called "latent" variables): these may be behaviors, attitudes, perceptions, motor and cognitive skills, knowledge, emotions, and the like. PRM frequently faces variables of this kind, the target of many interventions. Latent variables can only be observed through representative behaviors (e.g., walking for independence, moaning for pain, social isolation for depression, etc.). To measure them, behaviors are often listed and summated as items in cumulative questionnaires ("scales"). Questionnaires ultimately provide observations ("raw scores") with the aspect of numbers. Unfortunately, they are only a rough and often misleading approximation to true measures for various reasons. Measures should satisfy the same measurement axioms of physical sciences. In the present article, the flaws hidden in questionnaires' scores are summarised, and their consequences in outcome assessment are highlighted. The report should inspire a critical attitude in the readers and foster the interest in modern item response theory, with reference to Rasch analysis.
Efficacy and Safety of Biologic Agents for Lupus Nephritis
Authors: Chen Pang , Zhou Yadong , Wu Lianghua , Chen Shihan , Han Fangduo
Published: June 2022

Objectives

The aim of this study was to examine the effect and safety of biological agents for lupus nephritis (LN).

Methods

PubMed, EMBASE, and the Cochrane Library databases were searched from their inception up to November 2021. The outcomes were overall response, complete remission, proteinuria, renal activity index, and adverse events (AEs). Only randomized controlled trials (RCTs) were included.

Results

Nine RCTs (1645 patients) were included. The RCTs evaluated abatacept (n = 2), belimumab (n = 1), obinutuzumab (n = 1), atacicept (n = 1), IL-2 (n = 1), ocrelizumab (n = 1), and rituximab (n = 2). The use of biological agents was associated with higher likelihoods of achieving an overall response (relative risk [RR], 1.26; 95% confidence interval [CI], 1.15–1.39; p < 0.001; I
2 = 14.3%; p
Q = 0.301) and a complete response (RR, 1.33; 95% CI, 1.16–1.54; p < 0.001; I
2 = 41.8%; p
Q = 0.056). The use of biological agents was not associated with improvements in the urinary protein-to-creatinine ratio (weighted mean difference, 3.83; 95% CI, −3.71 to 11.38; p = 0.319; I
2 = 99.4%; p
Q < 0.001). The use of biological agents in patients with LN was also not associated with an increased risk of any AEs (RR, 1.01; 95% CI, 0.98–1.04; p = 0.519; I
2 = 0.0%; p
Q = 0.533), serious AEs (RR, 0.95; 95% CI, 0.82–1.09; p = 0.457; I
2 = 0.0%; p
Q = 0.667), grade >3 AEs (RR, 0.91; 95% CI, 0.67–1.22; p = 0.522; I
2 = 0.0%; p
Q = 0.977), infections (RR, 1.09; 95% CI, 0.99–1.20; p = 0.084; I
2 = 0.0%; p
Q = 0.430), and deaths (RR, 0.67; 95% CI, 0.36–1.24; p = 0.200; I
2 = 0.0%; p
Q = 0.439). The meta-regression analysis showed that follow-up duration and the sample size did not influence the complete response rate, whereas publications in 2012 to 2014 influence the rate compared with 2015 to 2020.

Conclusions

Biological agents seem to be effective and safe for managing patients with LN.
Dose Reduction and Image Quality in Photon-counting Detector High-resolution Computed Tomography of the Chest
Authors: Graafen Dirk , Emrich Tilman , Halfmann Moritz C. , Mildenberger Peter , Düber Christoph , Yang Yang , Othman Ahmed E. , O’ Doherty Jim , Müller Lukas , Kloeckner Roman
Published: June 2022

Purpose:

Photon-counting detector computed tomography (PCD-CT) has the potential to significantly improve CT imaging in many ways including, but not limited to, low-dose high-resolution CT (HRCT) of the lung. The aim of this study was to perform an intrapatient comparison of the radiation dose and image quality of PCD-CT compared with conventional energy-integrating detector CT (EID-CT).

Methods:

A total of 32 consecutive patients with available PCD-CT and EID-CT HRCT scans were included in the final analysis. The CT dose index (CTDIvol) was extracted from patient dose reports. Qualitative image analysis comprised the lung parenchyma and mediastinal structures and was assessed by 3 readers using a 5-point Likert scale. Quantitative image analysis included assessment of noise and signal-to-noise ratio in the lung parenchyma, trachea, aorta, muscle, and background.

Results:

The mean CTDIvol was 2.0 times higher in the conventional EID-CT scans (1.8±0.5 mGy) compared with PCD-CT (0.9±0.5 mGy, P<0.001). The overall image quality was rated significantly better by all 3 raters (P<0.001) in the PCD-CT relative to the EID-CT. Quantitative analysis showed no significant differences in noise and signal-to-noise ratio in the lung parenchyma between PCD-CT and EID-CT.

Conclusion:

Compared with conventional EID-CT scans, PCD-CT demonstrated similar or better objective and subjective image quality at significantly reduced dose levels in an intrapatient comparison. These results and their effect on clinical decision-making should be further investigated in prospective studies.
Pseudonocardia terrae sp. nov., an actinobacterium isolated from rice rhizosphere soil in Thailand
Authors: Muangham Supattra , Duangmal Kannika
Published: June 2022

A novel actinomycete, designated strain RS11V-5T, was isolated from rhizosphere soil of Oryza sativa L. collected from Roi Et Province, Thailand, and its taxonomic position was evaluated. Cells of strain RS11V-5T were Gram-stain-positive, aerobic, and non-motile. Whole-cell hydrolysates contained meso-diaminopimelic acid, arabinose, galactose, glucose and ribose. MK-8(H4) was detected as the predominant menaquinone of this strain. The polar lipids were diphosphatidylglycerol, phosphatidylmethylethanolamine, phosphatidylethanolamine, hydroxy-phosphatidylmethylethanolamine, hydroxy-phosphatidylethanolamine, an unidentified phospholipid, an unidentified aminolipid and an unidentified glycolipid. The major fatty acids were iso-C16 : 0, C16 : 0 and C16 : 1 ω7c/C16 : 1 ω6c. Phylogenetic analyses based on the 16S rRNA gene sequences showed that strain RS11V-5T belonged to the genus

Pseudonocardia

and had high 16S rRNA sequence similarity of 99.3 % to

Pseudonocardia kujensis

KCTC 29062T and less than 98.4 % to other members of the genus

Pseudonocardia

. The DNA G+C content of the strain RS11V-5T was 73.3 mol%. Strain RS11V-5T showed 46.5 % digital DNA–DNA hybridization, 92.2 % orthologous average nucleotide identity (OrthoANI), 90.2 % ANI based on blast and 92.7 % ANI based on MUMmer to

P. kujensis

KCTC 29062T. Based its phenotypic, genotypic, phylogenetic and chemotaxonomic characteristics, strain RS11V-5T represents a novel species of the genus

Pseudonocardia

, for which the name Pseudonocardia terrae sp. nov. is proposed. The type strain is RS11V-5T (=TBRC 15286T=NBRC 115296T).
Identification of Mucilaginibacter conchicola sp. nov., Mucilaginibacter achroorhodeus sp. nov. and Mucilaginibacter pallidiroseus sp. nov. and emended description of the genus Mucilaginibacter
Authors: Kim Jiyoun , Lee Byungjo , Chhetri Geeta , Kim Inhyup , So Yoonseop , Jang Wonhee , Seo Taegun
Published: June 2022

Three chitinolytic, Gram-negative, light pink, capsule-forming, rod-shaped bacterial strains with gliding motion (MYSH2T, MJ1aT and dk17T) were isolated from seashells, soil and foxtail, respectively. Phylogenetic analysis of the 16S rRNA gene sequences and concatenated alignment of 92 core genes indicated that strains MYSH2T, MJ1aT and dk17T were novel species of the genus

Mucilaginibacter

and exhibited a high 16S rRNA sequence similarity (i.e. more than 97.2 %) among each other. These novel strains contained summed feature 3 (C16:1 ω7c and/or C16:1 ω6), iso-C15:0 and MK-7 as the predominant fatty acids and menaquinone. According to the CAZys coding gene of KAAS, MYSH2T and MJ1aT were interpreted as strains containing both GH18 and 19 family coding genes, except for dk17T, which shows only GH19 family genes. These strains likely degrade chitin to chitobiose or directly to N-acetyl-d-glucosamine, which may enhance their chitinolytic capacity, thus making these stains potentially useful for industrial chitin degradation. Based on distinct morphological, physiological, chemotaxonomic and phylogenetic differences from their closest phylogenetic neighbours, we propose that strains MYSH2T, MJ1aT and dk17T represent three novel species in the genus

Mucilaginibacter

, for which the names Mucilaginibacter conchicola sp. nov. (=KACC 19716T=JCM 32787T), Mucilaginibacter achroorhodeus sp. nov. (=KACC 19906T=NBRC 113667T) and Mucilaginibacter pallidiroseus sp. nov. (=KACC 19907T=NBRC 113666T) are proposed. An emended description of the genus

Mucilaginibacter

is proposed.
Increased maternal non-oxidative energy metabolism mediates association between prenatal DEHP exposure and offspring ASD symptoms: a birth cohort study
Authors: Thomson Sarah , Drummond Katherine , O’Hely Martin , Symeonides Christos , Chandran Chitra , Mansell Toby , Saffery Richard , Sly Peter , Vuillermin Peter , Ponsonby Anne-Louise ,   the Barwon Infant Study Investigator Group
Published: June 2022

Prenatal phthalate exposure has previously been linked to the development of autism spectrum disorder (ASD). However, the underlying biological mechanisms remain unclear. We investigated whether maternal and child central carbon metabolism is involved as part of the Barwon Infant Study, a population-based birth cohort of 1074 Australian children. We estimated phthalate daily intakes using third-trimester urinary phthalate metabolite concentrations and other relevant indices. The metabolome of maternal serum in the third trimester, cord blood at birth and child plasma at 1 year were measured by nuclear magnetic resonance. We used the Small Molecule Pathway Database and principal component analysis to construct composite metabolite scores reflecting metabolic pathways. ASD symptoms at 2 and 4 years were measured by subscales of the Child Behavior Checklist and the Strengths and Difficulties Questionnaire, respectively. Multivariable linear regression analyses demonstrated (i) associations between higher prenatal di(2-ethylhexyl) phthalate (DEHP) levels and increased activity in maternal non-oxidative energy metabolism pathways, specifically non-oxidative pyruvate metabolism and the Warburg Effect, and (ii) associations between increased activity in these pathways and increased offspring ASD symptomology at 2 and 4 years of age. Mediation analyses suggested that part of the mechanism by which higher prenatal DEHP exposure influences the development of ASD symptoms in early childhood is through a maternal metabolic shift in pregnancy towards non-oxidative energy pathways, which are inefficient compared to oxidative metabolism. Interventions targeting maternal metabolic activity in pregnancy may be beneficial in reducing the potential risk to the developing fetus.
Genome-wide meta-analysis of over 29,000 people with epilepsy reveals 26 loci and subtype-specific genetic architecture
Authors:   International League Against Epilepsy Consortium on Complex Epilepsies, Berkovic Samuel F , Cavalleri Gianpiero L , Koeleman Bobby PC
Published: June 2022

Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here, we report a trans-ethnic GWAS including 29,944 cases, stratified into three broad- and seven sub-types of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants substantially close the missing heritability gap for GGE. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analysis of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current anti-seizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment.
Effect of HIV disease and the associated moderators on COVID-19 Mortality
Authors: Muthuka K. John , Muchiri W. Francis , Oluoch J. Kelly , Muchiri W. Francis , Nzioki M. Japheth
Published: June 2022

Introduction

Established predictors for COVID 19 related mortalities are diverse. The impact of these several risk factors on coronavirus mortality have been previously reported in several meta-analyses limited by small sample sizes and premature data. The objective of this systematic review and meta-analysis coupled with meta-regression was to evaluate the updated evidence on the risk of COVID 19 related mortality by HIV serostatus using published data, and account for possible moderators.

Method

Electronic databases including Google Scholar, Cochrane Library, Web of Sciences (WOS), EMBASE, Medline/PubMed, COVID 19 Research Database, and Scopus, were systematically searched till 30th February, 2022. All human studies were included irrespective of publication date or region. Twenty-two studies with a total of 19,783,097 patients detailing COVID 19 related mortality were included. To pool the estimate, a random effects model with risk ratio as the effect measure was used. Moreover, publication bias and sensitivity analysis were evaluated followed by meta-regression. The trial was registered (CRD42021264761) on the PROSPERO register.

Results

The findings were consistent in stating the contribution of HIV infection for COVID-19 related mortality. The cumulative COVID-19 related mortality was 110270 (0.6%) and 48863 (2.4%) with total events of 2010 (3.6%), 108260 (0.5%) among HIV-positive and negative persons respectively. HIV infection showed an increased risk of COVID-19 related mortality [RR=1.19, 95% CI (1.02, 1.39) (P=0.00001)] with substantial heterogeneity (I squared > 80%). The true effects size in 95% of all the comparable populations fell between 0.64 to 2.22. Multiple Centre studies and COVID-19 mortality with HIV infection showed a significant association [RR = 1.305, 95% CI (1.092, 1.559) (P = 0.003)], similar to studies conducted in America (RR=1.422, 95% CI 1.233, 1.639) and South Africa (RR=202;1.123, 95% CI 1.052, 1.198). HIV infection showed a risk for ICU admission [(P=0.00001) (I squared = 0%)] and mechanical ventilation [(P=0.04) (I squared = 0%)] which are predictors of COVID-19 severity prior to death. Furthermore, risk of COVID 19 related mortality is influenced by the region of study (R squared = 0.60). The variance proportion explained by covariates was significant (I squared = 87.5%, Q = 168.02, df = 21, p = 0.0000) (R squared = 0.67).

Conclusion

Our updated meta-analysis indicated that HIV infection was significantly associated with an increased risk for both COVID 19 mortality, which might be modulated by the regions. We believe the updated data further will contribute to more substantiation of the findings reported by similar earlier studies (Dong et al., 2021; K. W. Lee et al., 2021; Massarvva, 2021; Mellor et al., 2021; Ssentongo et al., 2021)
Neutralising antibodies predict protection from severe COVID-19
Authors: Cromer Deborah , Steain Megan , Reynaldi Arnold , Schlub Timothy E , Sasson Sarah C , Kent Stephen J , Khoury David S , Davenport Miles Philip
Published: June 2022

Background: Vaccine protection from COVID-19 has been shown to decline with time-since-vaccination and against SARS-CoV-2 variants. Protection against severe COVID-19 is higher than against symptomatic infection, and also appears relatively preserved over time and against variants. Although Protection protection from symptomatic SARS-CoV-2 infection has been shown to be strongly correlated with neutralising antibody titres, however, this relationship has been is less well described for severe COVID-19. Protection against severe COVID-19 is higher than against symptomatic infection, and also appears relatively preserved over time and against variants. Here we analyse whether neutralising antibody titre remains predictive of protection against severe COVID-19 in the face of waning neutralising antibody levels and emerging variants.
Methods: We extracted data from 15 studies reporting on protection against a range of SARS-CoV-2 clinical endpoints ("any infection", "symptomatic infection" and "severe COVID-19"). We then estimated the concurrent neutralising antibody titres using existing parameters on vaccine potency, neutralising antibody decay, and loss of recognition of variants and investigated the relationship between neutralising antibody titre and vaccine effectiveness against severe COVID-19.
Findings: Predicted neutralising antibody titres are strongly correlated with vaccine effectiveness against symptomatic and severe COVID-19 (Spearman rho = .94 and 0.63 respectively, p<.001 for both), consistent with previous estimates of the relationship between neutralisation and protection. Indeed 82% (137 of 167) of reported values of protection against severe COVID-19 across a range of vaccines and variants lie within the 95% confidence intervals of the published model.
Interpretation: Neutralising antibody titres are predictive of vaccine effectiveness against severe COVID-19 including in realistic scenarios of waning immunity and viral variants.
Funding: National Health and Medical Research Council (Australia), Medical Research Future Fund (Australia).
Cognitive features of amnestic Mild Cognitive Impairment using specific Cambridge Neuropsychological Test Automated Battery test scores
Authors: Tran-Chi Vinh-Long , Amrapala Arisara , Nantachai Gallayaporn , Hemrungrojn Solaphat , Tunvirachaisakul Chavit , Maes Michael
Published: June 2022

Background

In older adults with amnestic Mild Cognitive Impairment (aMCI), the Cambridge Neuropsychological Test Automated Battery (CANTAB) probes indicated cognitive impairments most frequently in memory.

Objectives

This study aimed to investigate a) the cognitive features of aMCI using memory CANTAB tests and b) whether the clinical diagnosis of aMCI can be externally validated by these CANTAB measurements.

Methods

We tested CANTAB tests that are specific to aMCI on 65 healthy controls and 66 people with aMCI who were diagnosed using Petersen’s criteria. These tests were spatial working memory (SWM), visual pattern recognition memory (PRM), delayed matching to sample (DSM), spatial span (SSP), and rapid visual information processing (RVP).

Results

The key aMCI features are impairments in PRM and DSM, whilst deficits in SSP and RVP are other, albeit somewhat less important features of aMCI. Nevertheless, neural network analyses including 10 CANTAB domains specific for MCI showed that only 70.8 percent of all subjects were properly identified with a sensitivity of 77.3%, specificity of 65.4% and an area under the ROC curve of 0.760. K-means cluster analysis using the same specific CANTAB test scores discovered 2 clusters with an adequate silhouette measure of cohesion and separation including a cluster with 36 subjects showing impairments in most neurocognitive tests.

Conclusion

Deficits in spatial working, pattern recognition and visuospatial working memory as well as rapid visual information processing are key features of aMCI. Nevertheless, the clinical diagnosis of aMCI according to Petersen’s criteria is overinclusive because too many healthy controls are allocated to this group.
Patterns of Physical Activity Over Time in Older Patients Rehabilitating after Hip Fracture Surgery: A Preliminary Study
Authors: van Dartel Dieuwke , Wang Ying , Hegeman Johannes H. , Vermeer Marloes , Vollenbroek-Hutten Miriam M.R.
Published: June 2022

Purpose

To investigate patterns of continuously monitored physical activity in older patients rehabilitating after hip fracture surgery and the association with patient characteristics.

Methods

Physical activity of surgically treated hip fracture patients (≥70 years) was continuously measured during rehabilitation at a skilled nursing home using an accelerometer. The intensity of physical activity per day was calculated to describe patients’ activity. Physical activity patterns of overall activity, overall variability, and day-to-day variability were investigated. Two experts in geriatric rehabilitation visually identified unique physical activity patterns for each aspect. Eighteen healthcare professionals independently classified each patient in one of the predefined patterns for each aspect. Differences between physical activity patterns and patient characteristics were assessed using a Kruskal-Wallis or Fisher’s Exact Test.

Results

Data from 66 patients were used. Six unique patterns were identified for overall activity and overall variability, and five for day-to-day variability. The most common pattern of overall activity and day-to-day variability first slowly increased, then steeply increased, and subsequently flattened (n=23,34.8%). For overall variability, the most common pattern first slowly increased, then steeply increased, then decreased and lastly increased (n=14,21.2%). Differences in functionality at rehabilitation admission, measured with the Barthel Index, and duration of rehabilitation stay were found between patterns of physical activity.

Conclusions

This preliminary study showed different patterns of physical activity among older hip fracture patients during rehabilitation. Functionality at rehabilitation admission and duration of rehabilitation stay were associated with these different patterns. Differences in physical activity patterns emphasize the importance of personalized hip fracture treatment
Evaluation of anti-SARS-CoV-2 antibody response to COVID-19 vaccine deployment in the Bono Region, Ghana
Authors: Gyasi Samuel Fosu , Donkoh Emmanuel Timmy , Frempong Samuel , Asamoah Akwasi , Raji Abdul Sakibu , Baidoo Rabbi Coffie , Isaac Williams , Essel Dorcas , Asakiya Herbert Alemiya
Published: June 2022

Background

Preliminary data across the globe shows that the AstraZeneca vaccine was highly effective in preventing not only the symptoms but also the transmission of the SARS-CoV-2 virus. In Ghana, data on the immune response generated by different vaccination doses is lacking. The present study aimed to compare the anti-SARS-CoV-2 antibody response among single and double-vaccinated versus unvaccinated individuals.

Methods

A case-control design was employed for this study. Seventy-nine participants (35 vaccinated, 44 unvaccinated) were recruited from the Sunyani West Municipality and screened for the presence of SARS-CoV-2 specific IgG and IgM antibodies in plasma samples using a Standard COVID IgG and IgM Combo FIA test. Data analysis was carried out with STATA (Version 21).

Results

The current study showed that mean IgG levels among vaccine groups (Group-1: Not vaccinated, Group-2: 1 dose, Group-3: 2 doses) differed significantly (F2, 76=11.457, p<.001) between Group-1 and Group-3; and between Group-2 and Group-3. Participants in Group-2 and Group-3 were 4.1 and 12.5 times more likely to develop more antibody responses compared to their counterparts in Group-1 respectively.

Conclusion

The study showed that participants who took one shot of the vaccine, as well as those who took two shots of the AstraZeneca Vaccine, were 4.1 and 12.5 times more likely to develop a greater antibody response than those who did not receive the vaccine respectively.
Accelerated waning of the humoral response to SARS-CoV-2 vaccines in obesity
Authors: van der Klaauw Agatha A. , Horner Emily C. , Pereyra-Gerber Pehuén , Agrawal Utkarsh , Foster William S. , Spencer Sarah , Vergese Bensi , Smith Miriam , Henning Elana , Ramsay Isobel D. , Smith Jack A. , Guillaume Stephane M. , Sharpe Hayley J. , Hay Iain M. , Thompson Sam , Innocentin Silvia , Booth Lucy H. , Robertson Chris , McCowan Colin , Mulroney Thomas E. , O’Reilly Martin J. , Gurugama Thevinya P. , Gurugama Lihinya P. , Rust Maria A. , Ferreira Alex , Ebrahimi Soraya , Ceron-Gutierrez Lourdes , Scotucci Jacopo , Kronsteiner Barbara , Dunachie Susanna J. , Klenerman Paul ,   PITCH Consortium, Park Adrian J. , Rubino Francesco , Stark Hannah , Kingston Nathalie , Doffinger Rainer , Linterman Michelle A. , Matheson Nicholas J. , Sheikh Aziz , Farooqi I. Sadaf , Thaventhiran James E. D.
Published: June 2022

Obesity is associated with an increased risk of severe Covid-19. However, the effectiveness of SARS-CoV-2 vaccines in people with obesity is unknown. Here we studied the relationship between body mass index (BMI), hospitalization and mortality due to Covid-19 amongst 3.5 million people in Scotland. Vaccinated people with severe obesity (BMI>40 kg/m2) were significantly more likely to experience hospitalization or death from Covid-19. Excess risk increased with time since vaccination. To investigate the underlying mechanisms, we conducted a prospective longitudinal study of the immune response in a clinical cohort of vaccinated people with severe obesity. Compared with normal weight people, six months after their second vaccine dose, significantly more people with severe obesity had unquantifiable titres of neutralizing antibody against authentic SARS-CoV-2 virus, reduced frequencies of antigen-experienced SARS-CoV-2 Spike-binding B cells, and a dissociation between anti-Spike antibody levels and neutralizing capacity. Neutralizing capacity was restored by a third dose of vaccine, but again declined more rapidly in people with severe obesity. We demonstrate that waning of SARS-CoV-2 vaccine-induced humoral immunity is accelerated in people with severe obesity and associated with increased hospitalization and mortality from breakthrough infections. Given the prevalence of obesity, our findings have significant implications for global public health.
Road environment characteristics and fatal crash injury during the rush hour period in the U.S.: Model testing and nested analytical study
Authors: Adeyemi Oluwaseun , Paul Rajib , Delmelle Eric , DiMaggio Charles , Arif Ahmed
Published: June 2022

Background

A substantial proportion of crash injuries occur during the rush-hour period. This study aims to assess the relationship between county-level road environmental characteristics and fatal road crash counts during the rush-hour period.

Method

We merged eight-year (2010 - 2017) data from the Fatality Analysis Reporting System. We limited the data to crashes during the rush hour period (6–9 am; 3– 7 pm). The outcome variable was the counts of fatal crashes per county. The predictor variables were road design (intersection, driveway, ramp, work-zone), road type (interstate, highways, roads/streets), and inclement weather factors (rain, fog, snow). A nested spatial negative binomial regression model was used to estimate the rate ratio of fatal crash injury during the rush-hour period, with estimated county population sizes used as the offset variable. Small area estimates, adjusted crash fatality rates, clusters, and outliers were visualized using choropleths maps.

Results

The median prevalence of rush-hour-related fatal crashes was 7.3 per 100,000 population. Case-specific fatality rates from interstates, highways, roads, streets, intersections, rain, fog, and snow were higher than the median fatality rates. Also, the median crash fatality rates were significantly higher in rural counties as compared to urban counties. During the rush-hour period, fatal crash injury rates were significantly elevated on interstates, highways, roads and streets, intersections, driveways, and work zones. Further, rain and fog were significantly associated with elevated fatal crash rates during the rush-hour period. Spatial clusters of fatal crash injuries were found in counties located in Idaho, Montana, Nevada, California, Wyoming, Utah, and across a few states in the Southeast.

Conclusion

Certain built, and natural road environment factors may influence crash injury rates during the rush-hour period.
Vaccine efficacy trials for Crimean-Congo haemorrhagic fever: insights from modelling different epidemiological settings
Authors: Vesga Juan F , Métras Raphaёlle , Clark Madeleine H A , Ayazi Edris , Apolloni Andrea , Leslie Toby , Msimang Veerle , Thompson Peter N. , Edmunds W John
Published: June 2022

Background

Crimean-Congo haemorrhagic fever (CCHF) is a priority emerging pathogen for which a licensed vaccine is not yet available. We aim to assess the feasibility of conducting phase III vaccine efficacy trials and the role of varying transmission dynamics.

Methods

We calibrate models of CCHF virus (CCHFV) transmission among livestock and spillover to humans in endemic areas in Afghanistan, Turkey and South Africa. We propose an individual randomised controlled trial targeted to high-risk population, and use the calibrated models to simulate trial cohorts to estimate the minimum trial endpoints necessary to analyse vaccine efficacy, sample size and follow-up time in the three settings.

Results

Under assumptions of a minimum vaccine efficacy of 60%, the minimum sample size needed to accrue the required 150 clinical endpoints in a minimum follow-up time of 6 months is estimated to be 34,000 (CrI 95%, 16,750 – 88,725) and 37,000 (CrI 95%, 13,000 – 77,250) in Afghanistan and Turkey, respectively. The results suggest that for South Africa the low endemic transmission levels will not permit achieving the necessary conditions for conducting this trial within a realistic follow-up time. In a scenario of CCHFV infection (rather than clinical case) as trial endpoint, the required sample size is reduced by 70% to 80% in Afghanistan and Turkey, and in South Africa, a trial becomes feasible for large sample sizes (>75,000) and vaccine efficacy of >70%. Increased expected vaccine efficacy >60% will reduce the required number of trial endpoints and thus the sample size and follow-time in phase III trials.

Conclusions

Underlying endemic transmission levels will play a central role in defining the feasibility of phase III vaccine efficacy trials. Endemic settings in Afghanistan and Turkey offer conditions under which such studies could feasibly be conducted.
Pruning and thresholding approach for methylation risk scores in multi-ancestry populations
Authors: Chen Junyu , Gatev Evan , Everson Todd , Conneely Karen N. , Koen Nastassja , Epstein Michael P. , Kobor Michael S. , Zar Heather J. , Stein Dan J. , Huels Anke
Published: June 2022

Recent efforts have focused on developing methylation risk scores (MRS), a weighted sum of the individual’s DNAm values of pre-selected CpG sites. Most of the current MRS approaches that utilize Epigenome-wide association studies (EWAS) summary statistics only include genome-wide significant CpG sites and do not consider co-methylation. New methods that relax the p-value threshold to include more CpG sites and account for the inter-correlation of DNAm might improve the predictive performance of MRS. We paired informed co-methylation pruning with P-value thresholding to generate pruning and thresholding (P+T) MRS and evaluated its performance among multi-ancestry populations. Through simulation studies and real data analyses, we demonstrated that pruning provides an improvement over simple thresholding methods for prediction of phenotypes. We demonstrated that European-derived summary statistics can be used to develop P+T MRS among other population such as African population. However, the prediction accuracy of P+T MRS may differ across multi-ancestry population due to environmental/cultural/social differences.
Availability, scope, and quality of monkeypox clinical management guidelines globally: a systematic review
Authors: Webb Eika , Rigby Ishmeala , Michelen Melina , Dagens Andrew , Cheng Vincent , Rojek Amanda , Dahmash Dania , Khader Susan , Gedela Keerti , Norton Alice , Cevik Muge , Cai Erhui , Harriss Eli , Lipworth Samuel , Nartowski Robert , Groves Helen , Hart Peter , Blumberg Lucille , Fletcher Tom , Jacob Shevin T , Sigfrid Louise , Horby Peter
Published: June 2022

Background

Monkeypox (MPX) is an important human orthopoxvirus infection. There has been an increase in MPX cases and outbreaks in endemic and non-endemic regions in recent decades. We appraised the availability, scope, quality, and inclusivity of clinical management guidelines for MPX globally.

Methods

For this systematic review, we searched six databases from inception until 14 Oct. 2021, augmented by a grey literature search until 17 May 2022. MPX guidelines providing treatment and supportive care recommendations were included, with no exclusions for language. Two reviewers assessed the guidelines. Quality was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool.

Results

Of 2026 records screened, 14 guidelines were included. Overall, most guidelines were of low-quality with a median score of 2 out of 7 (range: 1-7), lacked detail and covered a narrow range of topics. Most guidelines focused on adults, five (36%) provided some advice for children, three (21%) for pregnant women, and three (21%) for people living with HIV. Treatment guidance was mostly limited to advise on antivirals; seven guidelines advised cidofovir (four specified for severe MPX only); 29% (4/14) tecovirimat, and 7% (1/14) brincidofovir. Only one guideline provided recommendations on supportive care and treatment of complications. All guidelines recommended vaccination as post-exposure prophylaxis (PEP). Three guidelines advised on vaccinia immune globulin as PEP for severe cases in people with immunosuppression.

Conclusion

Our results highlight a concerning lack of evidence-based clinical management guidelines for MPX globally. There is a clear and urgent need for research into treatment and prophylaxis including for different risk populations. The current outbreak provides an opportunity to accelerate this research through coordinated high-quality studies. New evidence should be incorporated into globally accessible guidelines, to benefit patient and epidemic outcomes. A ‘living guideline’ framework is recommended.

Systematic review registration

PROSPERO CRD42020167361

Funding statement

This work was supported by the UK Foreign, Commonwealth and Development Office and Wellcome [215091/Z/18/Z] and the Bill & Melinda Gates Foundation [OPP1209135].
Factors associated with neuromusculoskeletal injury and disability in Navy and Marine Corps personnel
Authors: Fraser John J. , MacGregor Andrew J. , Fechner Kenneth M. , Galarneau Michael R.
Published: June 2022

Introduction

Neuromusculoskeletal injuries (NMSKI) are ubiquitous in the military, which contribute to short- and long-term disability.

Methods

NMSKI, limited duty (LIMDU), and long-term disability episode counts in the US Navy (USN) and Marine Corps (USMC) from December 2016 to August 2021 were extracted from the Musculoskeletal Naval Epidemiological Surveillance Tool. NMSKI, LIMDU, and long-term disability episodes incidence were calculated. A hurdle negative binomial regression evaluated the association of body region, sex, age, rank, age by rank, and service branch on NMSKI, LIMDU, and long-term disability incidence.

Results

From December 2016 to August 2021, there were 2004196 NMSKI episodes (USN: 3285/1000 Sailors; USMC: 4418/1000 Marines), 16791 LIMDU episodes (USN: 32/1000 Sailors; USMC: 29/1000 Marines), and 2783 long-term disability episodes (USN: 5/1000 Sailors; USMC: 5/1000 Marines). There was a large-magnitude protective effect on NMSKI during the pandemic (RR, USN: 0.70; USMC: 0.75). Low back and ankle-foot were the most ubiquitous, primarily affecting female personnel, aged 25-44 years, senior enlisted, in the USMC. Shoulder, arm, pelvis-hip, and knee conditions had the greatest risk for disability, with female sex, enlisted ranks, ages 18-24 years, and service in the USMC the most salient factors.

Discussion

The significant protective effect during the pandemic was likely a function of reduced physical exposure and access to non-urgent care. Geographically accessible specialized care and resources aligned with communities with the greatest risk is needed for the timely prevention, assessment, and treatment of NMSKI.

Conclusion

Body region, sex, age, rank, and branch were salient factors for NMSKI.
The impact of Test Positivity on Surveillance with Asymptomatic Carriers
Authors: Gaspari Mauro
Published: June 2022

Objectives

Recent studies show that Test Positivity Rate (TPR) gain a better correlation than incidence with the number of hospitalized patients in COVID-19 pandemic. Nevertheless, epidemiologist remain sceptical concerning the widespread use of this metric for surveillance, and indicators based on known cases like incidence are still preferred despite the large number of asymptomatic carriers which remain unknown. Our aim is to compare TPR and incidence, to determine which of the two has the best characteristics to predict the trend of hospitalized patients in COVID-19 pandemic.

Methods

We perform a retrospective study considering 60 cases, using global and local data from Italy in different waves of the pandemic, in order to detect peaks in TPR time series, and peaks in incidence, finding which of the two has the best ability to anticipate peaks in patients admitted in hospitals.

Results

On average the best TPR based approach anticipates incidence of about 4.6 days (95% CI 2.8, 6.4), more precisely the average distance between TPR peaks and hospitalized peaks is 17.6 days (95% CI 15.0, 20.4) with respect to 13.0 days (95% CI 10.4, 15.8) obtained for incidence. Moreover, the average difference between TPR and incidence increases to more than 6 days in the Delta outbreak during Summer 2021, where presumably the percentage of asymptomatic carriers was larger.

Conclusions

We conclude that TPR should be used as primary indicator to enable early intervention and for planning hospitals admissions in infectious diseases with asymptomatic carriers.
Obstructive sleep apnea is associated with specific gut microbiota species and functions in the population-based Swedish CardioPulmonary bioImage Study (SCAPIS)
Authors: Baldanzi Gabriel , Sayols-Baixeras Sergi , Theorell-Haglöw Jenny , Dekkers Koen F , Hammar Ulf , Nguyen Diem , Lin Yi-Ting , Ahmad Shafqat , Holm Jacob Bak , Nielsen Henrik Bjørn , Brunkwall Louise , Benedict Christian , Cedernaes Jonathan , Koskiniemi Sanna , Phillipson Mia , Lind Lars , Sundström Johan , Bergström Göran , Engström Gunnar , Smith J Gustav , Orho-Melander Marju , Ärnlöv Johan , Kennedy Beatrice , Lindberg Eva , Fall Tove
Published: June 2022

Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder. In animal models, OSA has been shown to alter the gut microbiota; however, little is known about such effects in humans. Here, we used respiratory polygraphy data from 3,570 individuals aged 50–64 from the Swedish CardioPulmonary bioImage Study (SCAPIS) and deep shotgun metagenomics to identify OSA-associated gut microbiota features. We found that OSA-related hypoxia parameters were associated with 128 bacterial species, including positive associations withBlautia obeumandCollinsela aerofacines. The latter was also associated with increased systolic blood pressure. Further, the cumulative time in hypoxia was associated with nine gut microbiota metabolic pathways, including propionate production from lactate, a biomarker of hypoxia. In conclusion, in this first large-scale study on gut microbiota alterations in OSA, we found that OSA-related hypoxia is associated with specific microbiota features. Our findings can direct future research on microbiota-mediated health effects of OSA.
A generalized ODE susceptible-infectious-susceptible compartmental model with potentially periodic behavior
Authors: Greenhalgh Scott , Dumas Anna
Published: June 2022

Differential equation compartmental models are crucial tools for forecasting and analyzing disease trajectories. Among these models, those dealing with only susceptible and infectious individuals are particularly useful as they offer closed-form expressions for solutions, such as the logistic equation. However, the logistic equation has limited ability to describe disease trajectories since its solutions must converge monotonically to either the disease-free or endemic equilibrium, depending on the parameters. Unfortunately, many diseases exhibit periodic cycles, and thus, do not converge to equilibria. To address this limitation, we developed a generalized susceptible-infectious-susceptible compartmental model capable of accurately incorporating the duration of infection distribution and describing both periodic and non-periodic disease trajectories. We characterized how our model’s parameters influence its behavior and applied the model to predict gonorrhea incidence in the US, using Akaike Information Criteria to inform on its merit relative to the classical SIS model and an SIS model with a time-varying recovery rate. The significance of our work lies in providing a novel susceptible-infected-susceptible model whose solutions can have closed-form expressions that may be periodic or non-periodic depending on the parameterization. Our work thus provides disease modelers with a straightforward way to investigate the potential periodic behavior of many diseases and thereby may aid ongoing efforts to prevent recurrent outbreaks.
Conserved gene signatures shared among MAPT mutations reveal defects in calcium signaling
Authors: Minaya Miguel A. , Mahali Sidhartha , Iyer Abhirami K. , Martinez Rita , Budde John , Temple Sally , Eteleeb Abdallah M. , Cruchaga Carlos , Harari Oscar , Karch Celeste M.
Published: June 2022

More than 50 mutations in the MAPT gene result in heterogeneous forms of frontotemporal lobar dementia with tau inclusions (FTLD-tau). However, early pathogenic events that lead to disease and the degree to which they are common across MAPT mutations remain poorly understood. The goal of this study is to determine whether there is a common molecular signature of FTLD-Tau. To do this, we analyzed genes differentially expressed in induced pluripotent stem cell (iPSC)–derived neurons that represent the three major categories of MAPT mutations: splicing (IVS10+16), exon 10 (p.P301L), and C-terminal (p.R406W) compared with isogenic controls. Here, we identified 275 genes that were commonly differentially expressed in MAPT IVS10+16, p.P301L, and p.R406W neurons. These genes were enriched in synaptic and endolysosomal pathways and neuronal development and were also altered in the presence of tau aggregation in a mouse model of tauopathy. The MAPT mutations commonly led to changes in genes and pathways sensitive to disruptions in calcium homeostasis. One of these genes, CALB1, plays a role in calcium dysregulation and is targeted by several FDA- approved drugs used to treat neurological symptoms. Finally, a subset of genes commonly differentially expressed across MAPT mutations were also dysregulated in brains from progressive supranuclear palsy patients, suggesting that molecular signatures relevant to genetic and sporadic forms of tauopathy are captured in a dish. The results from this study demonstrate that iPSC-derived neurons capture molecular processes that occur in human brains and can be used to pinpoint common molecular pathways involving synaptic and endolysosomal function and neuronal development, which may be regulated by disruptions in calcium homeostasis.