bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of predictors for terminal disease progression in simian immunodeficiency virus/simian-HIV-infected rhesus macaques
Authors: Takahashi Naofumi , Ardeshir Amir , Holder Gerard E. , Cai Yanhui , Sugimoto Chie , Mori Kazuyasu , Araínga Mariluz , He Ziyuan , Fukuyo Yayoi , Kim Woong-Ki , Didier Elizabeth S. , Kuroda Marcelo J.
Published: March 2021

Objectives:

CD4+ T-cell decline and increasing virus levels are considered hallmarks of HIV/AIDS pathogenesis but we previously demonstrated in rhesus macaques that tissue macrophage destruction by simian immunodeficiency virus (SIV) infection associated with increased monocyte turnover also appear to impact pathogenesis. It remains unclear, however, which factors best predict onset of terminal disease progression and survival time. The objective of this study, therefore, was to directly compare these co-variates of infection for predicting survival times in retrospective studies of SIV/simian-HIV (SHIV)-infected adult rhesus macaques

Methods:

Rhesus macaques were infected with various strains of SIV/SHIV and evaluated longitudinally for monocyte turnover, CD4+ T-cell loss, plasma viral load, and SIV/SHIV strain. Correlation analyses and machine learning algorithm modeling were applied to compare relative contributions of each of the co-variates to survival time.

Results:

All animals with AIDS-related clinical signs requiring euthanasia exhibited increased monocyte turnover regardless of CD4+ T-cell level, viral strain, or plasma viral load. Regression analyses and machine learning algorithms indicated a stronger correlation and contribution between increased monocyte turnover and reduced survival time than between CD4+ T-cell decline, plasma viral load, or virus strain and reduced survival time. Decision tree modeling categorized monocyte turnover of 13.2% as the initial significant threshold that best predicted decreased survival time.

Conclusion:

These results demonstrate that monocytes/macrophages significantly affect HIV/SIV pathogenesis outcomes. Monocyte turnover analyses are not currently feasible in humans, so there is a need to identify surrogate biomarkers reflecting tissue macrophage damage that predict HIV infection disease progression.
Racial, ethnic, and gender disparities in hospitalizations among persons with HIV in the United States and Canada, 2005–2015
Authors: Davy-Mendez Thibaut , Napravnik Sonia , Eron Joseph J. , Cole Stephen R. , Van Duin David , Wohl David A. , Gebo Kelly A. , Moore Richard D. , Althoff Keri N. , Poteat Tonia , Gill M. John , Horberg Michael A. , Silverberg Michael J. , Nanditha Ni Gusti Ayu , Thorne Jennifer E. , Berry Stephen A.
Published: March 2021

Objective:

To examine recent trends and differences in all-cause and cause-specific hospitalization rates by race, ethnicity, and gender among persons with HIV (PWH) in the United States and Canada.

Design:

HIV clinical cohort consortium.

Methods:

We followed PWH at least 18 years old in care 2005–2015 in six clinical cohorts. We used modified Clinical Classifications Software to categorize hospital discharge diagnoses. Incidence rate ratios (IRR) were estimated using Poisson regression with robust variances to compare racial and ethnic groups, stratified by gender, adjusted for cohort, calendar year, injection drug use history, and annually updated age, CD4+, and HIV viral load.

Results:

Among 27 085 patients (122 566 person-years), 80% were cisgender men, 1% transgender, 43% White, 33% Black, 17% Hispanic of any race, and 1% Indigenous. Unadjusted all-cause hospitalization rates were higher for Black [IRR 1.46, 95% confidence interval (CI) 1.32–1.61] and Indigenous (1.99, 1.44–2.74) versus White cisgender men, and for Indigenous versus White cisgender women (2.55, 1.68–3.89). Unadjusted AIDS-related hospitalization rates were also higher for Black, Hispanic, and Indigenous versus White cisgender men (all P < 0.05). Transgender patients had 1.50 times (1.05–2.14) and cisgender women 1.37 times (1.26–1.48) the unadjusted hospitalization rate of cisgender men. In adjusted analyses, among both cisgender men and women, Black patients had higher rates of cardiovascular and renal/genitourinary hospitalizations compared to Whites (all P < 0.05).

Conclusion:

Black, Hispanic, Indigenous, women, and transgender PWH in the United States and Canada experienced substantially higher hospitalization rates than White patients and cisgender men, respectively. Disparities likely have several causes, including differences in virologic suppression and chronic conditions such as diabetes and renal disease.
Tenofovir, pregnancy and renal function changes in pregnant women living with HIV
Authors: Thimm Matthew A. , Eke Ahizechukwu C.
Published: March 2021

This retrospective study of 100 pregnant women living with HIV [66 on tenofovir disoproxil fumarate (TDF) compared to 34 women on tenofovir alafenamide (TAF)] found no significant difference in renal function in pregnant women with HIV receiving TDF versus TAF. Our results demonstrate that, in regard to renal toxicity, both TDF and TAF appear to be safe for pregnant women living with HIV, but larger prospective cohort studies in pregnant women living with HIV are encouraged.
Comparative Study of Anthropometric Nasal Anslysis Based on Han Nationality Young Female Adults in Central China
Authors: Weiliang Zeng , Wei Wang , Lili Guo
Published: March 2021

Background:

The data of nasal anthropometric measurements could help surgeons perform preoperative or postoperative assessments and decide surgical strategies of the nose plastic surgery and related cosmetic rhinoplasty. The aim of the study was to describe the average values of the nasal anthropometric measurements in Han Nationality young female population in Central China.

Methods:

All 430 Han Chinese young females were obtained for this study, and their anthropometric features were measured including weight, height, 11 items of linear distance and 4 angles. Seven proportion indices of the soft tissue of the external nose were determined. Related results were compared with the result of other available literature about nasal anthropometry in Han Nationality young females from different regions of China and the other racial/ethnic nasal anthropometry in the world populations.

Results:

The means of the linear measurements of the external nose in this study were as follows: nasal height (48.9 mm), nasal bridge length (43.3 mm), morphological facial height (110.4 mm), facial width (125.1 mm), intercanthal width (35.9 mm), nasal tip protrusion (21.1 mm), nasal width (35.5 mm), nasal ala length (27.9 mm), nasal ala thickness (4.1 mm), columella height (8.9 mm), columella width (6.0 mm). The means of the angular measurements of the nose were as follows: nasofrontal angle (143.3 degree), nasofacial angle (34.1 degree), nasal tip angle (80.4 degree), nasolabial angle (97.3 degree).

Conclusions:

There were regional differences of the external nasal anthropometric of the Han Nationality young female adults in China and the racial/ethnic differences of that compared with the some races/ethnic around the world. This study could provide credible and objective reference material for plastic and maxillofacial surgeons for the external nasal soft tissue evaluation and planning of the cosmetic nasal surgery in the Han Nationality young female adults in Central China.
Finite Element Analysis of Two- and Three-Dimensional Fixation in Treating Mandibular Symphyseal Fracture Combined With Bilateral Condylar Intracapsular Fractures
Authors: Zhou Wei , Rong Qiguo , An Jingang , Zhang Yi
Published: March 2021

The aim of this study was to compare through finite element analysis two- and three-dimensional (2D and 3D) fixation in the treatment of mandibular symphyseal fracture combined with bilateral condylar intracapsular fractures. The authors created 2 fixation models for the above fracture, and analyzed the stress and displacement in the mandible and fixation materials under 3 loading conditions. The von Mises stress of the mandible and plates peaked during lateral occlusion, and was lowest during central occlusion. In all conditions, stresses in the fixation materials did not exceed the yield stress of titanium. The inferior border of the symphyseal fracture segments showed opposing displacements, and the mandible tended to widen in the 2D fixation model. However, the fracture displacement did not exceed 150 μm for either fixation method. The results suggested that after well reduction and fixation of condylar intracapsular fractures, either 2D or 3D fixation for symphyseal fracture can provide adequately strong fixation. Compared with 2D fixation, 3D fixation has more advantages in controlling the mandibular width and preventing the fixation materials from enduring excessive stress.
Single Free Flap for Large Defects in Head and Neck Reconstruction, Double Paddle Anterolateral Thigh Flap
Authors: Mohammadi Shabahang , Mohseni Mohammad , Mohebbi Saleh , Lotfi Maryam
Published: March 2021

The purpose of the study is to evaluate the efficacy of double skin paddle anterolateral thigh flap (ALT) to reconstruction of through and through oral cavity defect due to cancer surgery.

A prospective review was performed of patients referred to Firoozgar and Erfan hospitals with oral cavity defects with two or more oral cavity subunits and skin simultaneously involvement and immediate reconstruction using double-skin paddle ALT flap at the same time of tumor ablation from January 2019 to November 2020.

A total number of 6 patients was evaluated. The mean area of skin paddle was 110.4 cm2 and 92.8 cm2 in distal and proximal paddle respectively. Except one patient was complicated and expired in hospital admission, the remaining 5 patients got fully oral intake and completely survived flaps with primarily closed donor site. Tumor recurrence was not found in the mean follow-up time of 12 months.

The double skin paddle anterolateral thigh flap serves as an efficient reconstruction technique in complex and perforating oral cavity defects with the same functional outcome and the same flap related complications as conventional ALT flap.
Prevalence of Dentofacial Injuries and Concussions Among College Athletes and Their Perceptions of Mouthguards
Authors: Stanbouly Dani , Stanbouly Rami , Lee Kevin C. , Chuang Sung-Kiang
Published: March 2021

Purpose:

The purpose of this study was to determine the rates of dento-facial injuries and concussions among National Collegiate Athletic Association (NCAA) division 1 college athletes and their perceptions of mouth-guards and their protection role in injury prevention.

Materials and methods:

A specific survey regarding the experiences of dento-facial injuries and concussions, attitudes towards the mouthguards, and knowledge of dental first aid was distributed to 682 NCAA division I college athletes registered at Columbia University. The independent predictor variable was sport type (contact versus noncontact). The dependent outcome variables were dental injury rate, facial injury rate, concussion rate, mouthguard use, knowledge of dental first aid. Chi-squared and independent sample tests were used for statistical analysis.

Results:

The mean age of the athletes was 19.4 years (range: 17 to 22). 107 (47.6%) athletes were male. Only 62 (27.6%) athletes reported mouthguard use during gameplay. The most popular choice of mouthguard was the mouth-molded type (56.7%). Mouthguard use was significantly more prevalent among contact sport athletes (43.3% versus 1.2%; P < 0.01). Contact sport athletes were more likely to experience dental injuries (14.3% versus 0.0%; P < 0.01)., facial injuries (35.0% versus 6.2%; p < 0.01), and concussions (32.6% versus 2.4%; P < 0.01) relative to noncontact sport athletes. No significant difference was identified between contact and noncontact sport athletes with regards to knowledge of dental first aid.

Conclusions:

Contact sport athletes are significantly more inclined to suffer dento-facial injuries and concussions relative to noncontact sport athletes. Thus, mouthguard use and knowledge of dental first aid should be particularly reinforced amongst contact sport athletes.
Study on the Efficacy of Peracetic Acid Disinfectant (Type III) on Gastrointestinal Endoscopy Disinfection
Authors: Zhang Nan , Guo Jianqiang , Liu Lan , Wu Honglei , Gu Jiaoyang
Published: March 2021

Purpose:

The purpose of this study was to evaluate the disinfection efficacy of peracetic acid disinfectant (Type III) on gastrointestinal endoscopy.

Methods:

Endoscopes were disinfected, respectively, by 2% glutaraldehyde and peracetic acid disinfectant (Type III) according to the procedures stipulated by the 2016 version of “Regulation for cleaning and disinfection technique of flexible endoscope,” then samples were collected through biopsy channel at the specified steps. The bacterial count and pathogenic bacteria of these samples were detected, and hepatitis B virus surface antigen, hepatitis C virus antibody, and Treponemiapallidum antibody were detected by chemiluminescent microparticle immunoassay in peracetic acid disinfectant (Type III) group. The samples from the peracetic acid disinfectant (Type III) group were collected for 5 days continuously.

Results:

In total, 56 gastroscopes and 16 colonoscopes were disinfected by 2% glutaraldehyde (GA Group), 46 gastroscopes, and 15 colonoscopes were disinfected by peracetic acid disinfectant (Type III) (PAA Group). After disinfection, the bacterial count was significantly reduced in the 2 groups (P<0.05). In terms of the qualified rate of gastroscopes and total qualified rate, the PAA Group was better than GA Group [the qualified rate of gastroscopes: 97.83% (45/46) vs. 92.86% (52/56), P>0.05; total qualified rate: 98.36% (60/61) vs. 94.44% (68/72), P>0.05], the qualified rate of colonoscopes in the 2 groups were both 100.00% (15/15, 16/16). After disinfecting by peracetic acid disinfectant (Type III), hepatitis B virus surface antigen, anti-hepatitis C virus, and Treponemiapallidum antibody were negative. In term of colonies number detected for 5 days continuously, there was no significant difference at different collection steps (P>0.05).

Conclusions:

Peracetic acid disinfectant (Type III) can be well applied to clinical with meeting the standard of high-level disinfection for gastrointestinal endoscopy, and after disinfecting by peracetic acid disinfectant (Type III), there was no obvious bacterial residue in the biopsy channel.
Neurosyphilis and Lyme neuroborreliosis
Authors: Dersch Rick , Singh Ameeta E.
Published: March 2021

Purpose of review

Neurosyphilis (NS) and Lyme neuroborreliosis (LNB) are spirochetal diseases with distinct clinical manifestations. The diagnosis of NS remains challenging due to imperfect diagnostic criteria and testing modalities. With LNB, misconceptions about diagnosis and treatment lead to considerable morbidity and drug related adverse effects.

Recent findings

Although studies continue investigating alternate approaches and new diagnostic tests for NS, few data exist to change current approaches to diagnosis, management or follow up. In the diagnosis of LNB, the chemokine CXCL13 shows promising diagnostic accuracy. A systematic review discourages the use of cell-based assays when investigating Lyme disease. Clinical studies show no benefit from extended antibiotic treatment for patients with unspecific symptoms labelled as having Lyme disease.

The diagnosis of NS may be delayed due to a lack of specificity of findings, low suspicion for syphilis, and/or similarities in presentation to other diseases. A high index of suspicion for syphilis is required provide timely diagnosis and management of NS. Fortunately, penicillin remains the treatment of choice. Overdiagnosis and overtreatment in patients labelled as having Lyme disease can be avoided by an evidence-based approach towards diagnosis and treatment.
Medication overuse headache
Authors: Green Mark W.
Published: March 2021

Purpose of review

Medication overuse headache (MOH)is a disabling problem worldwide with areas of controversy regarding its cause. This article reviews the recent ideas regarding the development of this disorder and its effective management.

Recent findings

It has been proposed that all acute migraine medications can lead to MOH, with differences in the propensity of different agents to cause the problem. Early data suggests that gepants, which are small-molecule calcitonin gene-related peptide antagonists used for the acute treatment of migraine, may be an exception. Recent studies show that practitioners and the general public are still largely unaware of the problem of medication overuse and its damaging effects.

MOH is an accepted concept of an increase in headaches driven by the frequent administration of acute antimigraine drugs. The impressions of providers, and studies documenting the concept may be flawed. Although it is likely that MOH does occur, and restricting the amount of acute medications is necessary to prevent it, it is also possible that increasing amounts of acute medications are simply a reflection of poorly controlled headaches, rather than a cause. Objective markers need to be developed to identify those who have MOH, which does not include all with chronic migraine, and to use these markers in diagnosis and management, particularly in those patients where the frequent acute drugs might only be a reflection of frequent headaches, rather than a cause.
Predicting disability worsening in relapsing and progressive multiple sclerosis
Authors: Simmons Sarah B. , Schippling Sven , Giovannoni Gavin , Ontaneda Daniel
Published: March 2021

Purpose of review

Multiple sclerosis (MS) is a clinically heterogeneous disease, which complicates expectant management as well as treatment decisions. This review provides an overview of both well established and emerging predictors of disability worsening, including clinical factors, imaging factors, biomarkers and treatment strategies.

Recent findings

In addition to well known clinical predictors (age, male sex, clinical presentation, relapse behaviour), smoking, obesity, vascular and psychiatric comorbidities are associated with subsequent disability worsening in persons with MS. A number of imaging features are predictive of disability worsening and are present to varying degrees in relapsing and progressive forms of MS. These include brain volumes, spinal cord atrophy, lesion volumes and optical coherence tomography features. Cerebrospinal and more recently blood biomarkers including neurofilament light show promise as more easily attainable biomarkers of future disability accumulation. Importantly, recent observational studies suggest that initiation of early-intensive therapy, as opposed to escalation based on breakthrough disease, is associated with decreased accumulation of disability overall, although randomized controlled trials investigating this question are underway.

Understanding risk factors associated with disability progression can help to both counsel patients and enhance the clinician's availability to provide evidence-based treatment recommendations.
The functional polymorphisms linked with interleukin-1β gene expression are associated with bipolar disorder
Authors: Pu Xingfu , Li Jianghui , Ma Xiaoyuan , Yang Shunying , Wang Libo
Published: March 2021

Background

Bipolar disorder (BD) is a severe psychiatric illness attributable to multifactorial risk components (e.g. environmental stimuli, neuroinflammation, etc.), and genetic variations affecting these risk components are considered pivotal predisposing factors. The interleukin-1β (IL-1β) gene and its protein product have been repeatedly highlighted in the pathogenesis of BD. As functional polymorphisms and haplotypes linked with IL-1β mRNA expression have been reported, whether they are correlated with the risk of developing BD remains to be tested.

Methods

To examine whether variations in the IL-1β gene locus confer genetic risk of BD, we recruited 930 BD patients and 912 healthy controls for the current study. All subjects were Han Chinese, and were age- and gender-matched. We tested seven functional single nucleotide polymorphisms (SNPs) spanning the IL-1β gene and one haplotype composed of three SNPs for their associations with risk of BD.

Results

We found that the functional SNPs in the promoter region of IL-1β gene were significantly associated with risk of BD. The haplotype analyses further supported the involvement of IL-1β promoter SNPs in BD. The BD risk SNPs in our study have been previously reported to predict higher IL-1β levels in the brain and peripheral blood, which is consistent with the clinical observation of elevated IL-1β levels in the lymphocytes or peripheral blood of patients with BD compared with healthy subjects.

Conclusion

Our results support the contention that IL-1β is likely a risk gene for BD, and further investigations on this gene may promote our understanding and clinical management of this illness.
Characterization of novel Gluconobacter species from fruits and fermented food products: Gluconobacter cadivus sp. nov., Gluconobacter vitians sp. nov. and Gluconobacter potus sp. nov
Authors: Sombolestani Atena Sadat , Cleenwerck Ilse , Cnockaert Margo , Borremans Wim , Wieme Anneleen D. , De Vuyst Luc , Vandamme Peter
Published: March 2021

Strains LMG 1744T, LMG 1745, LMG 31484T, LMG 1764T and R-71646 were isolated from rotting fruits and fermented food products. A phylogenomic analysis based on 107 single-copy core genes revealed that they grouped in a

Gluconobacter

lineage comprising

Gluconobacter oxydans

,

Gluconobacter roseus

, Gluconobacter sphaericus, Gluconobacter kanchanaburiensis, Gluconobacter albidus, Gluconobacter cerevisiae, Gluconobacter kondonii and

Gluconobacter aidae

. OrthoANIu and digital DNA hybridization analyses demonstrated that these five strains represented three novel

Gluconobacter

species, which could be differentiated from the type strains of closely related

Gluconobacter

species by multiple phenotypic characteristics. We therefore propose to classify strains LMG 1744T and LMG 1745 in the novel species Gluconobacter cadivus sp. nov., with LMG 1744T (=CECT 30141T) as the type strain; to classify strain LMG 31484T as the novel species Gluconobacter vitians sp. nov., with LMG 31484T (=CECT 30132T) as the type strain; and to classify strains LMG 1764T and R-71646 in the novel species Gluconobacter potus sp. nov., with LMG 1764T (=CECT 30140T) as the type strain.
Outcome of Different Therapeutic Interventions in Mild COVID-19 Patients in a Single OPD Clinic of West Bengal: A Retrospective study
Authors: Roy Sayak , Samajdar Shambo Samrat , Tripathi Santanu K , Mukherjee Shatavisa , Bhattacharjee Kingshuk
Published: March 2021

Introduction

With over 87,273,380 cases being reported and 1,899,440 deaths worldwide as of 9th January 2021, Coronavirus disease 2019 (COVID-19) has become the worst-hit pandemic till date. Every day clinicians are bombarded with many new treatment options that claim to be better than the others.

Materials and methods

After screening the electronic database of COVID-19 patients retrospectively, 56 patients with mild COVID-19 infection matched the inclusion criteria and were divided into the four following groups - group having used Hydroxychloroquine (HCQ), group using doxycycline (DOX) + Ivermectin (IVR) combination, group receiving only azithromycin (AZ) and, group receiving only symptomatic treatment. The study’s primary objective was to see Clinical response of well-being (CRWB) reporting time after initiating treatment onset between the four different treatment arms.

Results

CRWB did not differ between the four groups receiving four different managements (p-value 0.846). There was significant correlation between blood levels of LDH (p-value 0.001), CRP (p-value 0.03) and D-dimer (p-value 0.04) with CRWB in IVR+DOX group and, between LDH (p-value 0.001), CRP (p-value 0.01) and age (p-value 0.035) with CRWB in the symptomatic management group.

Conclusion

Mild COVID-19 infection in patients having low-risk to progress can be managed symptomatically without any specific drug intervention.
Optimization of magnetic bead-based nucleic acid extraction for SARS-CoV-2 testing using readily available reagents
Authors: Haile Simon , Nikiforuk Aidan M. , Pandoh Pawan K. , Twa David D. W. , Smailus Duane E. , Nguyen Jason , Pleasance Stephen , Wong Angus , Zhao Yongjun , Eisler Diane , Moksa Michelle , Cao Qi , Wong Marcus , Su Edmund , Krzywinski Martin , Nelson Jessica , Mungall Andrew J. , Tsang Frankie , Prentice Leah M. , Jassem Agatha , Manges Amee R. , Jones Steven J. M. , Coope Robin J. , Prystajecky Natalie , Marra Marco A. , Krajden Mel , Hirst Martin
Published: March 2021

The COVID-19 pandemic has highlighted the need for generic reagents and flexible systems in diagnostic testing. Magnetic bead-based nucleic acid extraction protocols using 96-well plates on open liquid handlers are readily amenable to meet this need. Here, one such approach is rigorously optimized to minimize cross-well contamination while maintaining sensitivity.

Article Summary

A scalable, non-proprietary, magnetic bead-based automated nucleic acid extraction protocol optimised for minimum cross-well contamination
Disparities in the pace of biological aging among midlife adults of the same chronological age have implications for future frailty risk and policy
Authors: Elliott Maxwell L. , Caspi Avshalom , Houts Renate M. , Ambler Antony , Broadbent Jonathan M. , Hancox Robert J. , Harrington HonaLee , Hogan Sean , Keenan Ross , Knodt Annchen , Leung Joan H. , Melzer Tracy R. , Purdy Suzanne C. , Ramrakha Sandhya , Richmond-Rakerd Leah S. , Righarts Antoinette , Sugden Karen , Thomson W. Murray , Thorne Peter R. , Williams Benjamin S. , Wilson Graham , Hariri Ahmad R. , Poulton Richie , Moffitt Terrie E.
Published: March 2021

All humans age, but some age faster than others. Variation in biological aging can be measured in midlife, but the implications of this variation are poorly understood. We tested associations between biological aging and indicators of future frailty risk in the Dunedin cohort of 1037 infants born the same year and followed to age 45. Participants’ Pace of Aging was quantified by tracking declining function in 19 biomarkers indexing the cardiovascular, metabolic, renal, hepatic, immune, dental, and pulmonary systems across ages 26, 32, 38, and 45 years, in 2019. Participants with faster Pace of Aging had more cognitive difficulties, signs of advanced brain aging, diminished sensory-motor functions, older appearance, and more pessimistic perceptions of aging. People who are aging more rapidly than same-age peers in midlife may prematurely need supports to sustain independence that are usually reserved for older adults. Chronological age does not adequately identify need for such supports.
High-resolution epigenome analysis in nasal samples derived from children with respiratory viral infections reveals striking changes upon SARS-CoV-2 infection
Authors: Winkley Konner , Koseva Boryana , Banerjee Dithi , Cheung Warren , Selvarangan Rangaraj , Pastinen Tomi , Grundberg Elin
Published: March 2021

Background

DNA methylation patterns of the human genome can be modified by environmental stimuli and provide dense information on gene regulatory circuitries. We studied genome-wide DNA methylation in nasal samples from infants (<6 months) applying whole-genome bisulfite sequencing (WGBS) to characterize epigenome response to 10 different respiratory viral infections including SARS-CoV-2.

Results

We identified virus-specific differentially methylated regions (vDMR) with human metapneumovirus (hMPV) and SARS-CoV-2 followed by Influenza B (Flu B) causing the weakest vs. strongest epigenome response with 496 vs. 78541 and 14361 vDMR, respectively. We found a strong replication rate of FluB (52%) and SARS-CoV-2 (42%) vDMR in independent samples indicating robust epigenome perturbation upon infection. Among the FluB and SARS-CoV-2 vDMRs, around 70% were hypomethylated and significantly enriched among epithelial cell-specific regulatory elements whereas the hypermethylated vDMRs for these viruses mapped more frequently to immune cell regulatory elements, especially those of the myeloid lineage. The hypermethylated vDMRs were also enriched among genes and genetic loci in monocyte activation pathways and monocyte count. Finally, we perform single-cell RNA-sequencing characterization of nasal mucosa in response to these two viruses to functionally analyze the epigenome perturbations. Which supports the trends we identified in methylation data and highlights and important role for monocytes.

Conclusions

All together, we find evidence indicating genetic predisposition to innate immune response upon a respiratory viral infection. Our genome-wide monitoring of infant viral response provides first catalogue of associated host regulatory elements. Assessing epigenetic variation in individual patients may reveal evidence for viral triggers of childhood disease.
Evaluating the impacts of tiered restrictions introduced in England, during October and December 2020 on COVID-19 cases: A synthetic control study
Authors: Zhang Xingna , Owen Gwilym , Green Mark , Buchan Iain , Barr Ben
Published: March 2021

Background

In 2020, a second wave of COVID-19 cases unevenly affected places in England leading to the introduction of a tiered system of controls with different geographical areas subject to different levels of restrictions. Whilst previous research has examined the impact of national lockdowns on transmission, there has been limited research examining the marginal effect of differences in localised restrictions or how these effects vary between socioeconomic contexts. We therefore examined how Tier 3 restrictions in England implemented between October-December 2020, which included additional restrictions on the hospitality sector and people meeting outdoors affected COVID-19 case rates, compared to Tier 2 restrictions, and how these effects varied by level of deprivation.

Methods

We used data on weekly reported COVID-19 cases for 7201 neighbourhoods in England and adjusted these for changing case-detection rates to provide an estimate of weekly SARS-CoV-2 infections in each neighbourhood. We identified those areas that entered Tier 3 restrictions at two time points in October and December, and constructed a synthetic control group of similar places that had entered Tier 2 restrictions, using calibration weights to match them on a wide range of covariates that may influence transmission. We then compared the change in weekly infections between those entering Tier 3 to the synthetic control group to estimate the proportional reduction of cases resulting from Tier 3 restrictions compared to Tier 2 restrictions, over a 4-week period. We further used interaction analysis to estimate whether this effect differed based on the level of socioeconomic deprivation in each neighbourhood and whether effects were modified by the prevalence of a new more infectious variant of SARS-CoV-2 (B.1.1.7) in each area.

Results

The introduction of Tier 3 restrictions in October and December was associated with a 14% (95% CI 10% to 19%) and 20% (95% CI 13% to 29%) reduction in infections respectively, compared to the rates expected if only Tier 2 restrictions had been in place in those areas. We found that effects were similar across levels of deprivation and limited evidence that Tier 3 restrictions had a greater effect in areas where the new more infectious variant was more prevalent.

Interpretation

Additional restrictions on hospitality and meeting outdoors introduced in Tier 3 areas in England had a moderate effect on transmission and these restrictions did not appear to increase inequalities, having a similar impact across areas with differing levels of socioeconomic deprivation. Where transmission risks vary between geographical areas a tiered approach of local restrictions on outdoor mixing and hospitality can contribute to control of SARS-CoV-2 and is unlikely to increases inequalities in transmission.
Vaccine confidence and timeliness of childhood immunisation by health information source, maternal, socioeconomic, and geographic characteristics in Albania
Authors: Mayerová Daniela , Abbas Kaja
Published: March 2021

Background

Albania is facing decreasing childhood immunisation coverage and timeliness despite a growing economy and universal health insurance. Our aim is to estimate vaccine confidence and timeliness of childhood immunisation by health information source, maternal, socioeconomic, and geographic characteristics in Albania.

Methods

We used the 2017-2018 Albania Demographic and Health Survey to analyse vaccine confidence, measured via the proxy of vaccine timeliness, among 2,156 mothers of under-5-year-old children using simple and multivariable logistic regression.

Results

77.9% [74.2, 81.2] of mothers had confidence in vaccines. Immunisation delay was reported by 21.5% [18.3, 25.3] of mothers, but a majority (65.7%) were caused by the infant’s sickness at the time of vaccination, while a minority (8.7%) due to mothers’ concerns about vaccine safety and side effects. Among 1.7% of mothers who ever refused vaccination of their children, the main concerns were about vaccine safety (35.9%) and adverse events (42.7%). Factors associated with lower vaccine confidence were using the Internet/social media as the main health information source compared to other sources (AOR=0.66 [0.47, 0.94], p=0.020), mother’s work outside the home (AOR=0.65 [0.47, 0.91], p=0.013), lack of maternal education (AOR=0.14 [0.03, 0.67], p=0.014), and living in AL02-Qender (AOR=0.38 [0.23, 0.63]) and AL03-Jug regions (AOR=0.36 [0.24, 0.53]) in comparison to AL01-Veri region (p<0.0001).

Conclusions

Reinforcement of scientific evidence-based online communication about childhood immunisation and monitoring anti-vaccination movements on the Internet/social media would be beneficial in improving vaccine confidence and timeliness in Albania, together with traditional ways of promoting vaccination by healthcare professionals who enjoy confidence as trusted sources of information.
An observational cohort study on the incidence of SARS-CoV-2 infection and B.1.1.7 variant infection in healthcare workers by antibody and vaccination status
Authors: Lumley Sheila F , Rodger Gillian , Constantinides Bede , Sanderson Nicholas , Chau Kevin K , Street Teresa L , O’Donnell Denise , Howarth Alison , Hatch Stephanie B , Marsden Brian D , Cox Stuart , James Tim , Warren Fiona , Peck Liam J , Ritter Thomas G , de Toledo Zoe , Warren Laura , Axten David , Cornall Richard J , Jones E Yvonne , Stuart David I , Screaton Gavin , Ebner Daniel , Hoosdally Sarah , Chand Meera ,   Oxford University Hospitals Staff Testing Group, Crook Derrick W , O’Donnell Anne-Marie , Conlon Christopher P , Pouwels Koen B , Walker A Sarah , Peto Tim EA , Hopkins Susan , Walker Timothy M , Stoesser Nicole E , Matthews Philippa C , Jeffery Katie , Eyre David W
Published: March 2021

Background

Natural and vaccine-induced immunity will play a key role in controlling the SARS-CoV-2 pandemic. SARS-CoV-2 variants have the potential to evade natural and vaccine-induced immunity.

Methods

In a longitudinal cohort study of healthcare workers (HCWs) in Oxfordshire, UK, we investigated the protection from symptomatic and asymptomatic PCR-confirmed SARS-CoV-2 infection conferred by vaccination (Pfizer-BioNTech BNT162b2, Oxford-AstraZeneca ChAdOx1 nCOV-19) and prior infection (determined using anti-spike antibody status), using Poisson regression adjusted for age, sex, temporal changes in incidence and role. We estimated protection conferred after one versus two vaccinations and from infections with the B.1.1.7 variant identified using whole genome sequencing.

Results

13,109 HCWs participated; 8285 received the Pfizer-BioNTech vaccine (1407 two doses) and 2738 the Oxford-AstraZeneca vaccine (49 two doses). Compared to unvaccinated seronegative HCWs, natural immunity and two vaccination doses provided similar protection against symptomatic infection: no HCW vaccinated twice had symptomatic infection, and incidence was 98% lower in seropositive HCWs (adjusted incidence rate ratio 0.02 [95%CI <0.01-0.18]). Two vaccine doses or seropositivity reduced the incidence of any PCR-positive result with or without symptoms by 90% (0.10 [0.02-0.38]) and 85% (0.15 [0.08-0.26]) respectively. Single-dose vaccination reduced the incidence of symptomatic infection by 67% (0.33 [0.21-0.52]) and any PCR-positive result by 64% (0.36 [0.26-0.50]). There was no evidence of differences in immunity induced by natural infection and vaccination for infections with S-gene target failure and B.1.1.7.

Conclusion

Natural infection resulting in detectable anti-spike antibodies and two vaccine doses both provide robust protection against SARS-CoV-2 infection, including against the B.1.1.7 variant.

Natural infection resulting in detectable anti-spike antibodies and two vaccine doses both provided ≥ 85% protection against symptomatic and asymptomatic SARS-CoV-2 infection in healthcare workers, including against the B.1.1.7 variant. Single dose vaccination reduced symptomatic infection by 67%.
Leg-heel chest compression as an alternative for medical professionals in times of COVID-19
Authors: Ott Matthias , Krohn Alexander , Bilfield Laurence H. , Dengler F. , Jaki C. , Echterdiek F. , Schilling T , Heymer J.
Published: March 2021

Objective

To evaluate leg-heel chest compression without previous training as an alternative for medical professionals and its effects on distance to potential aerosol spread during chest compression.

Methods

20 medical professionals performed standard manual chest compression followed by leg-heel chest compression after a brief instruction on a manikin. We compared percentage of correct chest compression position, percentage of full chest recoil, percentage of correct compression depth, average compression depth, percentage of correct compression rate and average compression rate between both methods. In a second approach, potential aerosol spread during chest compression was visualized.

Results

There was no significant difference between manual and leg-heel compression. The distance to potential aerosol spread could have been increased by leg-heel method.

Conclusion

Under special circumstances like COVID-19-pandemic, leg-heel chest compression may be an effective alternative without previous training compared to manual chest compression while markedly increasing the distance to the patient.
COVID-19 mRNA Vaccination in Lactation: Assessment of adverse events and vaccine related antibodies in mother-infant dyads
Authors: Golan Yarden , Prahl Mary , Cassidy Arianna G. , Gay Caryl , Wu Alan H.B. , Jigmeddagva Unurzul , Lin Christine Y. , Gonzalez Veronica J. , Basilio Emilia , Warrier Lakshmi , Buarpung Sirirak , Li Lin , Murtha Amy P. , Asiodu Ifeyinwa V. , Ahituv Nadav , Flaherman Valerie J. , Gaw Stephanie L.
Published: March 2021

Background

Data regarding adverse events observed in the lactating mother-infant dyad and their immune response to COVID-19 mRNA vaccination during lactation are needed to inform vaccination guidelines.

Methods

From a prospective cohort of 50 lactating individuals who received mRNA-based vaccines for COVID-19 (mRNA-1273 and BNT162b2), blood and milk samples were collected prior to first vaccination dose, immediately prior to 2nd dose, and 4-10 weeks after 2nd dose. Symptoms in mother and infant were assessed by detailed questionnaires. Anti-SARS-CoV-2 antibody levels in blood and milk were measured by Pylon 3D automated immunoassay and ELISA. In addition, vaccine-related PEGylated proteins in milk were measured by ELISA. Blood samples were collected from a subset of infants whose mothers received the vaccine during lactation (4-15 weeks after mothers’ 2nd dose).

Results

No severe maternal or infant adverse events were reported in this cohort. Two mothers and two infants were diagnosed with COVID-19 during the study period. PEGylated proteins, were not found at significant levels in milk after vaccination. After vaccination, levels of anti-SARS-CoV-2 IgG and IgM significantly increased in maternal plasma and there was significant transfer of anti-SARS-CoV-2-Receptor Binding Domain (anti-RBD) IgA and IgG antibodies to milk. Milk IgA levels after the 2nd dose were negatively associated with infant age. Anti-SARS-CoV-2 IgG antibodies were not detected in the plasma of infants whose mothers were vaccinated during lactation.

Conclusions

COVID-19 mRNA vaccines generate robust immune responses in plasma and milk of lactating individuals without severe adverse events reported.
Evaluation of anti-SARS-CoV-2 antibody testing in asymptomatic or mild COVID-19 patients in outbreak on a cruise ship
Authors: Kaku Norihito , Nishimura Fumitaka , Shigeishi Yui , Tachiki Rina , Sakai Hironori , Sasaki Daisuke , Ota Kenji , Sakamoto Kei , Kosai Kosuke , Hasegawa Hiroo , Izumikawa Koichi , Ariyoshi Koya , Mukae Hiroshi , Yasuda Jiro , Morita Kouichi , Kohno Shigeru , Yanagihara Katsunori
Published: March 2021

Background

A few studies on antibody testing have focused on asymptomatic or mild coronavirus disease 2019 (COVID-19) patients with low initial anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody responses. Anti-SARS-CoV-2 antibody-testing performance was evaluated using blood samples from asymptomatic or mild COVID-19 patients.

Methods

Blood samples were collected from 143 COVID-19 patients during an outbreak on a cruise ship 3 weeks after diagnosis. Simultaneously, a second SARS-CoV-2 genetic test was performed. Samples stored before the COVID-19 pandemic were also used to evaluate the lateral flow immunochromatographic assay (LFA) and electrochemiluminescence immunoassay (ECLIA). Titers of anti-SARS-CoV-2 IgM and IgG antibodies against the nucleocapsid and spike proteins were measured using the enzyme-linked immunosorbent assay to compare false-negative- with positive-result samples.

Results

Sensitivity, specificity, positive-predictive, and negative-predictive values of LFA-detected IgM antibodies were 0.231, 1.000, 1.000, and 0.613, respectively; those of LFA-detected IgG antibodies were 0.483, 0.989, 0.972, and 0.601, respectively; and those of ECLIA-detected total antibodies were 0.783, 1.000, 1.000, and 0.848, respectively. IgM-, IgG-, and total-antibody positivity rates in the patients with negative results from the second genetic testing were 22.9%, 47.6%, and 72.4%, respectively. All antibody titers, especially those of the IgG antibody against nucleocapsid protein, were significantly lower in blood samples with false-negative results than in those with positive results.

Conclusions

These findings suggest that anti-SARS-CoV-2 antibody testing has lower performance in asymptomatic or mild COVID-19 patients than required in the guidelines, and situations in which it is useful are limited.

Key points

Anti-SARS-CoV-2 antibody testing in asymptomatic or mild COVID-19 patients is lower than the required clinical sensitivity, although it may be useful in patients at 3–4 weeks after symptom onset but with negative SARS-CoV-2 genetic test results.
The importance of a consistent workflow to estimate muscle-tendon lengths based on joint angles from the conventional gait model
Authors: Kainz Hans , Schwartz Michael H
Published: March 2021

Background

Musculoskeletal models enable us to estimate muscle-tendon length, which has been shown to improve clinical decision-making and outcomes in children with cerebral palsy. Most clinical gait analysis services, however, do not include muscle-tendon length estimation in their clinical routine. This is due, in part, to a lack of knowledge and trust in the musculoskeletal models, and to the complexity involved in the workflow to obtain the muscle-tendon length.

Research question

Can the joint angles obtained with the conventional gait model (CGM) be used to generate accurate muscle-tendon length estimates?

Methods

Three-dimensional motion capture data of 15 children with cerebral palsy and 15 typically developing children were retrospectively analyzed and used to estimate muscle-tendon length with the following four modelling frameworks: (1) 2392-OSM-IK-angles: standard OpenSim workflow including scaling, inverse kinematics and muscle analysis; (2) 2392-OSM-CGM-angle: generic 2392-OpenSim model driven with joint angles from the CGM; (3) modif-OSM-IK-angles: standard OpenSim workflow including inverse kinematics and a modified model with segment coordinate systems and joint degrees-of-freedom similar to the CGM; (4) modif-OSM-CGM-angles: modified model driven with joint angles from the CGM. Joint kinematics and muscle-tendon length were compared between the different modelling frameworks.

Results

Large differences in hip joint kinematics were observed between the CGM and the 2392-OpenSim model. The modif-OSM showed similar kinematics as the CGM. Muscle-tendon length obtained with modif-OSM-IK-angles and modif-OSM-CGM-angles were similar, whereas large differences in some muscle-tendon length were observed between 2392-OSM-IK-angles and 2392-OSM-CGM-angles.

Significance

The modif-OSM-CGM-angles framework enabled us to estimate muscle-tendon lengths without the need for scaling a musculoskeletal model and running inverse kinematics. Hence, muscle-tendon length estimates can be obtained simply, without the need for the complexity, knowledge and time required for musculoskeletal modeling and associated software. An instruction showing how the framework can be used in a clinical setting is provided on https://github.com/HansUniVie/MuscleLength.
Evaluation of Measles Surveillance System amidst Covid – 19 pandemic in Asutifi North District, Ahafo Region, Ghana
Authors: Owusu Sekyere Stephen , Dam-Park Laar Salam
Published: March 2021

Background

Measles is a disease of public health importance earmarked for elimination by all WHO Regions. Globally, more than 140 000 people died from Measles in 2018 affecting mostly children under 5 years, despite the availability of safe and effective vaccine.

Methods

A descriptive cross-sectional survey was conducted. Disease surveillance focal persons were interviewed using semi-structured questionnaire on the system operations and use of Measles case definitions. Measles case-based investigation forms from 2015 – 2020 were reviewed for its timeliness and data quality. CDC updated guidelines for surveillance system evaluation was used to assess its usefulness and attributes. Data was analyzed for frequencies and proportions and results presented in tables and graphs.

Results

Measles surveillance system was timely as 100% (69/69) of the suspected cases were reported on time. Also, the level of representativeness was good as all the 14 health facilities in the District were participating in the Measles Surveillance system. Majority 73.1 (44/60) of the case-based investigation forms filled were incomplete with some columns wrongly filled.

Conclusion

Despite the outbreak of Covid – 19 with most districts battling with how to contain the virus, measles surveillance system was still meeting its objectives of early detection and prompt reporting but with poor data quality.