bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved 18-FDG PET/CT diagnosis of multiple myeloma diffuse disease by radiomics analysis
Authors: Mesguich Charles , Hindie Elif , de Senneville Baudouin Denis , Tlili Ghoufrane , Pinaquy Jean-Baptiste , Marit Gerald , Saut Olivier
Published: May 2021

Objectives

In multiple myeloma, the diagnosis of diffuse bone marrow infiltration on 18-FDG PET/CT can be challenging. We aimed to develop a PET/CT radiomics-based model that could improve the diagnosis of multiple myeloma diffuse disease on 18-FDG PET/CT.

Methods

We prospectively performed PET/CT and whole-body diffusion-weighted MRI in 30 newly diagnosed multiple myeloma. MRI was the reference standard for diffuse disease assessment. Twenty patients were randomly assigned to a training set and 10 to an independent test set. Visual analysis of PET/CT was performed by two nuclear medicine physicians. Spine volumes were automatically segmented, and a total of 174 Imaging Biomarker Standardisation Initiative-compliant radiomics features were extracted from PET and CT. Selection of best features was performed with random forest features importance and correlation analysis. Machine-learning algorithms were trained on the selected features with cross-validation and evaluated on the independent test set.

Results

Out of the 30 patients, 18 had established diffuse disease on MRI. The sensitivity, specificity and accuracy of visual analysis were 67, 75 and 70%, respectively, with a moderate kappa coefficient of agreement of 0.6. Five radiomics features were selected. On the training set, random forest classifier reached a sensitivity, specificity and accuracy of 93, 86 and 91%, respectively, with an area under the curve of 0.90 (95% confidence interval, 0.89–0.91). On the independent test set, the model achieved an accuracy of 80%.

Conclusions

Radiomics analysis of 18-FDG PET/CT images with machine-learning overcame the limitations of visual analysis, providing a highly accurate and more reliable diagnosis of diffuse bone marrow infiltration in multiple myeloma patients.
Improving adherence to daily preexposure prophylaxis among MSM in Amsterdam by providing feedback via a mobile application
Authors: van den Elshout Mark A.M. , Hoornenborg Elske , Achterbergh Roel C.A. , Coyer Liza , Anderson Peter L. , Davidovich Udi , de Vries Henry J.C. , Prins Maria , van der Loeff Maarten F. Schim
Published: May 2021

Objective:

Improving adherence to preexposure prophylaxis (PrEP) by providing automated feedback on self-reported PrEP use via a mobile application (app).

Design:

Randomized clinical trial among MSM participating in the Amsterdam PrEP demonstration project (AMPrEP).

Methods:

Eligible participants were randomized 1 : 1 to the control or intervention app. Both allowed daily reporting of sexual behaviour and medication intake; the intervention app also provided visual feedback. Dried blood spots collected at 12 and 24 months yielded intracellular tenofovir diphosphate concentrations (TFV-DP). We assessed proportions of participants with poor (TFV-DP <700 fmol/punch; primary outcome), good (TFV-DP ≥700 fmol/punch) and excellent (TFV-DP ≥1250 fmol/punch; secondary outcome) adherence at both time-points, and the association with the control or intervention app.

Results:

We randomized 229 participants, 118 to the intervention and 111 to the control arm. The primary, per-protocol, analysis included 83 participants per arm. In total, 22/166 (13%) of participants adhered poorly, 144/166 (87%) good and 66/166 (40%) excellently. App feedback did not result in a lower proportion of participants with poor adherence [control: 9 of 83 (11%); intervention: 13 of 83 (16%); P = 0.36]. App feedback did result in a larger proportion of participants with excellent adherence [control: 26/83 (31%); intervention: 40/83 (48%); P = 0.026].

Conclusion:

In this highly adherent population, app feedback did not improve the proportion of participants with poor adherence to PrEP.

Clinical Trial Number Netherlands Trial Register: NL5413.
Transconjunctival Lower Blepharoplasty Using Midcheek Spaces for Orbital Fat Transposition (S.O.F.T.)
Authors: Jin Yunbo , Gao Wei , Teo Honeylen Maryl T. , Lin Xiaoxi
Published: May 2021

Background

The subperiosteum, supraperiosteum, and intrasuborbicularis oculi fat have been used as planes of dissection for orbital fat transposition in transconjunctival lower blepharoplasty. The steep learning curve due to the anatomic complexity in using any of the 3 planes may deter plastic surgeons from performing the procedure. We present the use of clear anatomical midcheek spaces, the premaxillary and prezygomatic spaces, as the plane for orbital fat transposition in transconjunctival lower blepharoplasty.

Methods

We performed a retrospective study of 184 consecutive patients who underwent transconjunctival orbital fat transposition using the midcheek spaces from November 2013 to July 2019. Recorded data included the patient's age, duration of surgery, postoperative complications (chemosis; bleeding; lower eyelid swelling; orbital and/or lower eyelid infection; eye misalignment on primary gaze; binocular diplopia; numbness involving the lower eyelid, cheek, and upper lip; orbicularis oculi paralysis, inferior scleral show, and lower eyelid ectropion), aesthetic result, and patient satisfaction.

Results

The mean age is 35.48 ± 6.66 years. Significant aesthetic improvement was achieved not only for herniated orbital fat and prominent lid-cheek junction but also for midcheek depression over an average follow-up of 22.41 ± 16.04 months. The patient satisfaction score (98.91%) was high. No major complications occurred. The mean operating time was 46.74 ± 6.67 minutes.

Conclusions

The natural midcheek spaces could be used as an ideal plane for orbital fat transposition in transconjunctival lower blepharoplasty. By using the midcheek spaces, transconjunctival orbital fat transposition can become a safe and effective technique without the steep learning curve.
Converging public health crises: substance use during the coronavirus disease 2019 pandemic
Authors: Striley Catherine W. , Hoeflich Carolin C.
Published: May 2021

Purpose of review

The international, public health crisis caused by the rapid spread of SARS-CoV-2 has resulted in unforeseen medical and psychiatric consequences. We reviewed publications from January 2020 to January 2021, given that earlier documents were not relevant, to review findings on changes in substance use and overdoses during the pandemic. Additionally, this review of the literature also documents advocacy efforts, health service modification and challenges, as well as COVID-related health complications associated with substance use.

Recent findings

Recent work focused on identifying changes in the distribution and use of substances as well as the unique challenges to promoting the health of persons who use substances in the current pandemic. Although COVID-19 has triggered unprecedented innovations in the organizational and public policy, the use of certain substances (alcohol, cannabis, cigarettes, fentanyl, heroin, and opiates) is increasing internationally. Unique associations between substance use and pandemic-related adverse health outcomes were identified. In addition, the pandemic precipitated significant barriers and disruptions to care.

Given increased overdose rates and infections among people who use drugs, continued surveillance and vigilance are needed to assess changes and reduce use and adverse consequences during the continuing COVID-19 crisis. Changes are urgently needed to reduce adverse health outcomes because of treatment barriers and lack of adequate treatment options. Additionally, integrative approaches are necessary to promote the public health of persons who use substances.
Episodes of opposing survival and reproductive selection cause strong fluctuating selection on seasonal migration versus residence
Authors: Acker Paul , Burthe Sarah J. , Newell Mark A. , Grist Hannah , Gunn Carrie , Harris Michael P. , Payo-Payo Ana , Swann Robert , Wanless Sarah , Daunt Francis , Reid Jane M.
Published: May 2021

Quantifying temporal variation in sex-specific selection on key ecologically relevant traits, and quantifying how such variation arises through synergistic or opposing components of survival and reproductive selection, is central to understanding eco-evolutionary dynamics, but rarely achieved. Seasonal migration versus residence is one key trait that directly shapes spatio-seasonal population dynamics in spatially and temporally varying environments, but temporal dynamics of sex-specific selection have not been fully quantified. We fitted multi-event capture–recapture models to year-round ring resightings and breeding success data from partially migratory European shags (
Phalacrocorax aristotelis
) to quantify temporal variation in annual sex-specific selection on seasonal migration versus residence arising through adult survival, reproduction and the combination of both (i.e. annual fitness). We demonstrate episodes of strong and strongly fluctuating selection through annual fitness that were broadly synchronized across females and males. These overall fluctuations arose because strong reproductive selection against migration in several years contrasted with strong survival selection against residence in years with extreme climatic events. These results indicate how substantial phenotypic and genetic variation in migration versus residence could be maintained, and highlight that biologically important fluctuations in selection may not be detected unless both survival selection and reproductive selection are appropriately quantified and combined.
A critical evaluation of the index of patch quality
Authors: Fayet Annette L. , Houston Alasdair I.
Published: May 2021

The inverse optimality approach can allow us to learn about an animal's environment by assuming their behaviour is optimal. This approach has been applied to animals diving underwater for food to produce the index of patch quality (IPQ), which aims to provide a proxy for prey abundance or quality in a foraging patch based on the animal's diving behaviour. The IPQ has been used in several empirical studies but has never been evaluated theoretically. Here, we discuss the strengths and weaknesses of the IPQ approach from a theoretical angle and review the empirical evidence supporting its use. We highlight several potential issues, in particular with the gain function—the function describing the energetic gain of an animal during a dive—used to calculate the IPQ. We investigate an alternative gain function which is appropriate in some cases, provide a new model based on this function, and discuss differences between the IPQ model and ours. We also find that there is little supporting empirical evidence justifying the general use of the IPQ and suggest future empirical validation methods which could help strengthen the case for the IPQ. Our findings have implications for the field of diving ecology and habitat assessment.
Epidemiological characteristics and incubation period of SARS-CoV-2 during the 2020-2021 winter pandemic wave in north China: an observational study
Authors: Liu Tiantian , Chen Zijian , Xu Jin
Published: May 2021

As the emergence of new variants of SARS-CoV-2 persists across the world, it is of importance to understand the distributional behavior of incubation period of the variants for both medical research and public health policy-making. We collected the published individual level data of 941 patients of the 2020-2021 winter pandemic wave in Hebei province, north China. We computed some epidemiological characteristics of the wave and estimated the distribution of the incubation period. We further assessed the covariate effects of sex, age and living with a case with respect to incubation period by a model. The infection-fatality rate was only 0.1%. The estimated median incubation period was at least 22 days, significantly extended from the estimates (ranging from 4 to 8.5 days) of the previous wave in mainland China and those ever reported elsewhere around the world. The proportion of asymptomatic patients was 90.6%. No significant covariate effect was found. The distribution of incubation period of the new variants showed a clear extension from their early generations.
The SARS-CoV-2 B.1.351/V2 variant is outgrowing the B.1.1.7/V1 variant in French regions in April 2021
Authors: Roquebert Bénédicte , Trombert-Paolantoni Sabine , Haim-Boukobza Stéphanie , Lecorche Emmanuel , Verdurme Laura , Foulongne Vincent , Sofonea Mircea T. , Alizon Samuel
Published: May 2021

SARS-CoV-2 variants threaten our ability to control COVID-19 epidemics. We analyzed 36,590 variant-specific RT-PCR tests performed on samples collected between April 12 and May 7, 2021 in France to compare variant spread. Contrarily to January to March 2021, we found that the V2 variant had a significant transmission advantage over V1 in some regions (15.1 to 16.1% in Île-de-France and 16.1 to 18.8% in Hauts-de-France). This shift in transmission advantage is consistent with the immune evasion abilities of V2 and the high levels of immunization in these regions.
Effective clinical caseload management strategies from the perspective of community consultant psychiatrist: Qualitative analysis
Authors: Warikoo Nishchint , Demirdogen Ezgi Sen
Published: May 2021

Objective

There is a lack of guidance and literature on determining a safe caseload size and how community consultant psychiatrists (CCPs) manage their caseload. This paper therefore aims at exploring effective and safe ways of clinical caseload management by gaining a qualitative understanding of caseload management (CLM) practice of CCPs.

Design

Cross sectional Qualitative research using semi structured interviews.

Setting

The participants were CCPs working in National health service in Hampshire areas of United Kingdom.

Participants

The target population comprised 11 CCPs working in the National Health Service (NHS) to get their view on current practice in NHS and compare past and present practices of CLM.

Main Outcome Measures

A qualitative research method was used to explore the topic of CLM by collecting data through observations, interviews, questionnaires and then analysing the data using the coding and emergent themes method.

Results

Caseload size for CCPs was higher than a manageable level and had an impact on their ability to service their other responsibilities such as strategic work; they did not have a shared view on setting a limit to their caseload. Majority of CCPs were not using CLM and did not have enough control on limiting their caseload size. Some CCPs were using time management and audit of caseload as effective CLM strategies. NWW was not being used equitably.

Conclusions

Although the study represents the perceptions of limited number of CCPs, the findings of this study are unique and an important addition to the slight literature that exists on this topic. The results were in line with existing research that large caseloads can have negative impact on CCPs and their ability to provide effective care to the clients. The key factors determining the caseload size were highlighted. Proactive time management and proactive caseload size management were found to be effective tools for CLM. These supported by job planning meetings, Yearly appraisal, use of electronic data system and New ways of Working could be effective in maintaining a safe caseload size for the provision of safe and effective care. The data from this study can be used for requisite quantitative studies on a larger and statistically significant number of CCPs to find effectiveness of each CLM strategy.
A common allele of HLA mediates asymptomatic SARS-CoV-2 infection
Authors: Augusto Danillo G. , Yusufali Tasneem , Sabatino Joseph J. , Peyser Noah D. , Murdolo Lawton D. , Butcher Xochitl , Murray Victoria , Pae Vivian , Sarvadhavabhatla Sannidhi , Beltran Fiona , Gill Gurjot , Lynch Kara , Yun Cassandra , Maguire Colin , Peluso Michael J. , Hoh Rebecca , Henrich Timothy J. , Deeks Steven G. , Davidson Michelle , Lu Scott , Goldberg Sarah A. , Kelly J. Daniel , Martin Jeffrey N. , Viera-Green Cynthia A. , Spellman Stephen R. , Langton David J. , Lee Sulggi , Marcus Gregory M. , Olgin Jeffrey E. , Pletcher Mark J. , Gras Stephanie , Maiers Martin , Hollenbach Jill A.
Published: May 2021

Despite some inconsistent reporting of symptoms, studies have demonstrated that at least 20% of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will remain asymptomatic. Although most global efforts have focused on understanding factors underlying severe illness in COVID-19 (coronavirus disease of 2019), the examination of asymptomatic infection provides a unique opportunity to consider early disease and immunologic features promoting rapid viral clearance. Owing to its critical role in the immune response, we postulated that variation in the human leukocyte antigen (HLA) loci may underly processes mediating asymptomatic infection. We enrolled 29,947 individuals registered in the National Marrow Donor Program for whom high-resolution HLA genotyping data were available in the UCSF Citizen Science smartphone-based study designed to track COVID-19 symptoms and outcomes. Our discovery cohort (n=1428) was comprised of unvaccinated, self-identified subjects who reported a positive test result for SARS-CoV-2. We tested for association of five HLA loci (HLA-A, -B, -C, -DRB1, -DQB1) with disease course and identified a strong association of HLA-B*15:01 with asymptomatic infection, and reproduced this association in two independent cohorts. Suggesting that this genetic association is due to pre-existing T-cell immunity, we show that T cells from pre-pandemic individuals carrying HLA-B*15:01 were reactive to the immunodominant SARS-CoV-2 S-derived peptide NQKLIANQF, and 100% of the reactive cells displayed memory phenotype. Finally, we characterize the protein structure of HLA-B*15:01-peptide complexes, demonstrating that the NQKLIANQF peptide from SARS-CoV-2, and the highly homologous NQKLIANAF from seasonal coronaviruses OC43-CoV and HKU1-CoV, share similar ability to be stabilized and presented by HLA-B*15:01, providing the molecular basis for T-cell cross-reactivity and HLA-B*15:01-mediated pre-existing immunity.
KL-MOB: Automated Covid-19 Recognition Using a Novel Approach Based on Image Enhancement and a Modified MobileNet CNN
Authors: Taresh Mundher Mohammed , Zhu Ningbo , Ali Ali Talal Ahmed , Alghaili Mohammed , Hameed Asaad Shakir , Mutar Modhi Lafta
Published: May 2021

The emergence of the novel coronavirus pneumonia (Covid-19) pandemic at the end of 2019 led to chaos worldwide. The world breathed a sigh of relief when some countries announced that they had obtained the appropriate vaccine and gradually began to distribute it. Nevertheless, the emergence of another wave of this disease has returned us to the starting point. At present, early detection of infected cases has been the paramount concern of both specialists and health researchers. This paper aims to detect infected patients through chest x-ray images. The large dataset available online for Covid-19 (COVIDx) was used in this research. The dataset consists of 2,128 x-ray images of Covid-19 cases, 8,066 normal cases, and 5,575 cases of pneumonia. A hybrid algorithm was applied to improve image quality before conducting the neural network training process. This algorithm consisted of combining two different noise reduction filters in the images, followed by a contrast enhancement algorithm. In this paper, for Covid-19 detection, a novel convolution neural network (CNN) architecture, KL-MOB (Covid-19 detection network based on MobileNet structure), was proposed. KL-MOB performance was boosted by adding the Kullback–Leibler (KL) divergence loss function at the end when trained from scratch. The Kullback–Leibler (KL) divergence loss function was adopted as content-based image retrieval and fine-grained classification to improve the quality of image representation. This paper yielded impressive results, overall benchmark accuracy, sensitivity, specificity, and precision of 98.7%, 98.32%, 98.82%, and 98.37%, respectively. The promising results in this research may enable other researchers to develop modern and innovative methods to aid specialists. The tremendous potential of the method proposed in this research can also be utilized to detect Covid-19 quickly and safely in patients throughout the world.
Caesarean birth in public maternities in Argentina: a formative research study on the views of obstetricians, midwives, and trainees
Authors: Perrotta Carla , Romero Mariana , Sguassero Yanina , Straw Cecilia , Gialdini Celina , Righetti Natalia , Beltrán Ana Pilar , Ramos Silvina
Published: May 2021

Objectives

To explore obstetricians, midwives, and trainees’ perceptions of CS determinants in the context of public obstetric care services provision in Argentina. Our hypothesis is that known determinants of CS use may differ in settings with limited access to essential obstetric services.

Setting

We conducted a formative research study in nineteen public maternity hospitals in Argentina. An institutional survey assessed the availability of essential obstetric services. Subsequently, we conducted online surveys and semi-structured interviews to assess the opinions of providers on known CS determinants.

Results

Obstetric services showed an adequate provision of emergency obstetric care but limited services to support women during birth. Midwives, with some exceptions, are not involved during labour. We received 680 surveys from obstetricians, residents, and midwives (response rate of 63%) and interviewed 26 key informants. Six out of ten providers (411, 61%) indicated that the use of CS is associated with the complexities of our caseload. Limited pain management access was deemed a potential contributing factor for CS in adolescents and first-time mothers. Providers have conflicting views on the adequacy of training to deal with complex or prolonged labour Obstetricians with more than ten years of clinical experience indicated that fear of litigation was also associated with CS. Overall, there is consensus on the need to implement interventions to reduce unnecessary CS.

Conclusions

Public Maternity Hospitals in Argentina have made significant improvements in the provision of emergency services. The environment of service provision does not seem to facilitate the physiological process of vaginal birth. Providers acknowledged some of those challenges.

Article Summary

Strengths and limitations of this study

This study is one of the few studies exploring the perceptions of providers working in low-resourced settings in middle-income countries on the determinants of increasing trends of CS.

Large sample and representation of all professionals and obstetric tasks working in low-resourced settings.

Cluster analysis allowed to describe the response variability across professional groups in relation to specific CS determinants.

The use of Formative Research is a valuable tool to inform the design and implementation of future interventions.

Even though the response rate is good (63%) those who did not respond may have different views on the determinants of CS.

Some participant hospitals had lower response rate.
Regional distribution of anoxic brain injury after cardiac arrest: clinical and electrographic correlates
Authors: Snider Samuel B. , Fischer David , McKeown Morgan E. , Cohen Alexander L. , Schaper Frederic L.W.V.J. , Amorim Edilberto , Fox Michael D. , Scirica Benjamin , Bevers Matthew B. , Lee Jong W.
Published: May 2021

Introduction

Disorders of consciousness, EEG background suppression and epileptic seizures are associated with poor outcome after cardiac arrest. The underlying patterns of anoxic brain injury associated with each remain unknown. Our objective was to identify the distribution of anoxic brain injury after cardiac arrest, as measured with diffusion MRI, and to define the regional correlates of disorders of consciousness, EEG background suppression, and seizures.

Methods

We analyzed patients from a prospectively-maintained, single-center database of unresponsive patients who underwent diffusion-weighted MRI following cardiac arrest (n = 204). We classified each patient based on recovery of consciousness (command-following) before discharge, the most continuous EEG background (burst suppression versus continuous), and the presence or absence of seizures. Anoxic brain injury was measured using the apparent diffusion coefficient (ADC) signal. We identified abnormalities in ADC relative to control subjects without cardiac arrest (n = 48) and used voxel lesion symptom mapping to identify regional associations with disorders of consciousness, EEG background suppression, and seizures. We then used a bootstrapped lasso regression procedure to identify robust, multivariate regional associations with each clinical and EEG variable. Finally, using area under receiver operating characteristic curves, we then compared the classification ability of the strongest regional associations to that of brain-wide summary measures.

Results

Compared to control subjects, cardiac arrest patients demonstrated a reduction in the ADC signal that was most significant in the occipital lobes. Disorders of consciousness were associated with reduced ADC most prominently in the occipital lobes, but also in the basal ganglia, medial thalamus and cerebellar nuclei. Regional injury more accurately classified patients with disorders of consciousness than whole-brain injury. Background suppression mapped to a similar set of brain regions, but regional injury could no better classify patients than whole-brain measures. Seizures were less common in patients with more severe anoxic injury, particularly in those with injury to the lateral temporal white matter.

Discussion

Anoxic brain injury was most prevalent in posterior cerebral regions, and this regional pattern of injury was a better predictor of disorders of consciousness than whole-brain injury measures. EEG background suppression lacked a specific regional association, but patients with injury to the temporal lobe were less likely to have seizures. Collectively, our results suggest that the regional pattern of anoxic brain injury is relevant to the clinical and electrographic sequelae of cardiac arrest and may hold importance for prognosis.
SARS-CoV-2 infection risk during delivery of childhood vaccination campaigns: a modelling study
Authors: Procter Simon R , Abbas Kaja , Flasche Stefan , Griffiths Ulla , Hagedorn Brittany , O’Reilly Kathleen M ,   CMMID COVID-19 Working Group, Jit Mark
Published: May 2021

Background

The COVID-19 pandemic has disrupted delivery of immunisation services globally. Many countries have postponed vaccination campaigns out of concern about infection risks to staff delivering vaccination, the children being vaccinated and their families. The World Health Organization recommends considering both the benefit of preventive campaigns and the risk of SARS-CoV-2 transmission when making decisions about campaigns during COVID-19 outbreaks, but there has been little quantification of the risks.

Methods

We modelled excess SARS-CoV-2 infection risk to vaccinators, vaccinees and their caregivers resulting from vaccination campaigns delivered during a COVID-19 epidemic. Our model used population age-structure and contact patterns from three exemplar countries (Burkina Faso, Ethiopia, and Brazil). It combined an existing compartmental transmission model of an underlying COVID-19 epidemic with a Reed-Frost model of SARS-CoV-2 infection risk to vaccinators and vaccinees. We explored how excess risk depends on key parameters governing SARS-CoV-2 transmissibility, and aspects of campaign delivery such as campaign duration, number of vaccinations, and effectiveness of personal protective equipment (PPE) and symptomatic screening.

Results

Infection risks differ considerably depending on the circumstances in which vaccination campaigns are conducted. A campaign conducted at the peak of a SARS-CoV-2 epidemic with high prevalence and without special infection mitigation measures could increase absolute infection risk by 32% to 45% for vaccinators, and 0.3% to 0.5% for vaccinees and caregivers. However, these risks could be reduced to 3.6% to 5.3% and 0.1% to 0.2% respectively by use of PPE that reduces transmission by 90% (as might be achieved with N95 respirators or high-quality surgical masks) and symptomatic screening.

Conclusions

SARS-CoV-2 infection risks to vaccinators, vaccinees and caregivers during vaccination campaigns can be greatly reduced by adequate PPE, symptomatic screening, and appropriate campaign timing. Our results support the use of adequate risk mitigation measures for vaccination campaigns held during SARS-CoV-2 epidemics, rather than cancelling them entirely.
Symptom profiles and accuracy of clinical definitions for COVID-19 in the community. Results of the Virus Watch community cohort
Authors: Fragaszy Ellen , Shrotri Madhumita , Geismar Cyril , Aryee Anna , Beale Sarah , Braithwaite Isobel , Byrne Thomas , Fong Wing Lam Erica , Gibbs Jo , Hardelid Pia , Kovar Jana , Lampos Vasileios , Nastouli Eleni , Navaratnam Annalan M D , Nguyen Vincent , Patel Parth , Aldridge Robert W , Hayward Andrew
Published: May 2021

Background

Understanding the symptomatology and accuracy of clinical case definitions for COVID-19 in the community is important for the initiation of Test, Trace and Isolate (TTI) and may, in future, be important for early prescription of antivirals.

Methods

Virus Watch is a large community cohort with prospective daily recording of a wide range of symptoms and self-reporting of swab results (mainly undertaken through the UK TTI system). We compared frequency, severity, timing, and duration of symptoms in test positive and test negative cases. We compared the test performance of the current UK case definition used by TTI (any one of: new continuous cough, high temperature, or loss of or altered sense of smell or taste) with a wider definition that also included muscle aches, chills, headache, or loss of appetite.

Findings

We included results from 8213 swabbed illnesses, 944 of which tested positive for SARS-CoV-2. All symptoms were more common in test positive than test negative illnesses and symptoms were also more severe and of longer duration. Common symptoms such as cough, headache, fatigue, muscle aches, and loss of appetite occurred early in the course of illness but were also very common in test-negative illnesses. In contrast, high temperature and loss of or altered sense of smell or taste were less frequently identified in swab positive illnesses but were markedly more common than in swab negative illnesses. The current UK definition had a sensitivity and specificity of 81% and 47% respectively for symptomatic COVID-19 compared to 93% and 26% for the broader definition. On average, cases met the broader case definition 0.3 days earlier than the current definition. 1.7-fold more illnesses met the broader definition than the current case definition.

Interpretation

COVID-19 is difficult to distinguish from other respiratory infections and common ailments on the basis of symptoms. Broadening the list of symptoms used to encourage engagement with TTI could moderately increase the number of infections identified and shorten delays to isolation, but with a large increase in the number of tests needed and the number of unwell individuals and contacts who are advised to self-isolate whilst awaiting results, and subsequently test negative for SARS-CoV-2.
Comparison of respiratory protection during exercising tasks between different wearing methods of replaceable particulate respirators and powered air-purifying respirators
Authors: Baba Hiroka , Ando Hajime , Ikegami Kazunori , Sekoguchi Shingo , Shirasaka Taiki , Ogami Akira
Published: May 2021

Background

This study evaluated the differences in respiratory protection between replaceable particulate respirators (RPRs) and powered air-purifying respirators (PAPRs), with different wearing methods, during exercising tasks.

Methods

Ten participants wore either RPR or PAPR according to the recommended method, with a knit cover placed between the facepiece cushion and the face, or with the headband on a helmet. We measured the number of particles inside and outside the respiratory protective equipment (RPE) during exercising tasks for each wearing variation. The exercise state was set to exercise with an ergometer set at 80W load. While exercising tasks, the participants performed five actions adopted from JIS T8150 in 2018 (1. Normal breathing, 2. Deep breathing, 3. Turning head side to side, 4. Moving head up and down, 5. Talking). Each action was performed for 1 min. For measurements of exercise state, after 10 minutes of exercise tasks, we measured while the exercise was continued. The fit factor was calculated by dividing the concentration within the RPE by the concentration outside of it. Data were analyzed after they were log-transformed with a linear mixed model, with fit factor as the dependent variable.

Results

We compared the results with experimental data of resting state reported in our previous studies. Fit factor of RPRs in the exercise state was significantly lower (p<0.001) than that in the resting state, indicating inadequate respiratory protection. In contrast, the fit factor of PAPRs during exercising tasks was significantly lower (p<0.001) than that at rest; however, respiratory protection was maintained. PAPR did not show a significant decrease (p=1.000) in fit factor owing to the wearing variations during exercising tasks.

Conclusions

PAPRs were found to be superior to RPRs in terms of respiratory protection. PAPRs are better than RPRs for workers who have to wear RPE inappropriately due to health problems.
Persistence of functional memory B cells recognizing SARS-CoV-2 variants despite loss of specific IgG
Authors: Winklmeier Stephan , Eisenhut Katharina , Taskin Damla , Rübsamen Heike , Schneider Celine , Eichhorn Peter , Keppler Oliver T. , Klein Matthias , Mader Simone , Kümpfel Tania , Meinl Edgar
Published: May 2021

While some COVID-19 patients maintain SARS-CoV-2-specific serum IgGs for more than 6 months post-infection, others, especially mild cases, eventually lose IgG levels. We aimed to assess the persistence of SARS-CoV-2-specific B cells in patients who have lost specific IgGs and analyzed the reactivity of the immunoglobulins produced by these B cells. Circulating IgG memory B cells specific for SARS-CoV-2 were detected in all 16 patients 1–8 months post-infection, and 11 participants had specific IgA B cells. Four patients lost specific serum IgG after 5–8 months but had SARS-CoV-2-specific-B-cell levels comparable to those of seropositive donors. Immunoglobulins produced after in vitro differentiation blocked receptor-binding domain (RBD) binding to the cellular receptor ACE-2, indicating neutralizing activity. Memory-B-cell-derived IgGs recognized the RBD of B.1.1.7 similarly to the wild-type, while reactivity to B.1.351 and P.1. decreased by 30% and 50%, respectively. Memory-B-cell differentiation into antibody-producing cells is a more sensitive method for detecting previous infection than measuring serum antibodies. Circulating SARS-CoV-2 IgG memory B cells persist, even in the absence of specific serum IgG; produce neutralizing antibodies; and show differential cross-reactivity to emerging variants of concern. These features of SARS-CoV-2-specific memory B cells will help to understand and promote long-term protection.
Systematic Review and Meta-analysis on COVID-19 Vaccine Hesitancy
Authors: Fathalla Aboelsaad Iman Ahmed , Hafez Dina Mohamed , Almaghraby Abdallah , Abdulmoneim Shaimaa Abdulaziz , El-ganainy Samar Ossama , Hamdy Noha Alaa , Deghidy Ehsan Akram , El-Deen Ahmed El-Sayed Nour , Adel Elrewany Ehab Mohamed , Taha Khalil Alaa Hamdy , Salem Karem Mohamed , kabeel Samar Galal , Mohammed Elhadi Yasir Ahmed , Shaaban Ramy , Alnagar Amr , Fadel Elsherbeny Eman Ahmad , Elfeshawy Nagwa Ibrahim , Tahoun Mohamed Moustafa , Ghazy Ramy Mohamed
Published: May 2021

Background:

The presented meta-analysis was developed in response to the publication of several studies addressing COVID-19 vaccines hesitancy. We aimed to identify the proportion of vaccine acceptance and rejection, and factors affecting vaccine hesitancy worldwide especially with the fast emergency approval of vaccines.

Methods:

Online database search was performed, and relevant studies were included with no language restriction. A meta-analysis was conducted using R software to obtain the random effect model of the pooled prevalence of vaccine acceptance and rejection. Egger’s regression test was performed to assess publication bias. Quality assessment was assessed using Newcastle-Ottawa Scale quality assessment tool.

Results:

Thirty-nine out of 12246 articles met the predefined inclusion criteria. All studies were cross-sectional designs. The pooled proportion of COVID-19 vaccine hesitancy was 17% (95% CI: 14-20) while the pooled proportion of COVID-19 vaccine acceptance was 75% (95% CI: 71-79). The vaccine hesitancy and the vaccine acceptance showed high heterogeneity (I2=100%). Case fatality ratio and the number of reported cases had significant effect on the vaccine acceptance as the pooled proportion of vaccine acceptance increased by 39.95% (95% CI: 20.1-59.8) for each 1% increase in case fatality (P<0.0001) and decreased by 0.1% (95% CI: -0.2-0.01) for each 1000 reported case of COVID-19, P= 0.0183).

Conclusion:

Transparency in reporting the number of newly diagnosed COVID-19 cases and deaths is mandatory as these factors are the main determinants of COVID-19 vaccine acceptance.
Two-phase sample selection strategies for design and analysis in post-genome wide association fine-mapping studies
Authors: Espin-Garcia Osvaldo , Craiu Radu V. , Bull Shelley B.
Published: May 2021

Post-GWAS analysis, in many cases, focuses on fine-mapping targeted genetic regions discovered at GWAS-stage; that is, the aim is to pinpoint potential causal variants and susceptibility genes for complex traits and disease outcomes using next-generation sequencing (NGS) technologies. Large-scale GWAS cohorts are necessary to identify target regions given the typically modest genetic effect sizes. In this context, two-phase sampling design and analysis is a cost-reduction technique that utilizes data collected during phase 1 GWAS to select an informative subsample for phase 2 sequencing. The main goal is to make inference for genetic variants measured via NGS by efficiently combining data from phases 1 and 2. We propose two approaches for selecting a phase 2 design under a budget constraint. The first method identifies sampling fractions that select a phase 2 design yielding an asymptotic variance covariance matrix with certain optimal characteristics, e.g. smallest trace, via Lagrange multipliers (LM). The second relies on a genetic algorithm (GA) with a defined fitness function to identify exactly a phase 2 subsample. We perform comprehensive simulation studies to evaluate the empirical properties of the proposed designs for a genetic association study of a quantitative trait. We compare our methods against two ranked designs: residual-dependent sampling and a recently identified optimal design. Our findings demonstrate that the proposed designs, GA in particular, can render competitive power in combined phase 1 and 2 analysis compared to alternative designs while preserving type 1 error control. These results are especially apparent under the more practical scenario where design values need to be defineda prioriand are subject to mispecification. We illustrate the proposed methods in a study of triglyceride levels in the North Finland Birth Cohort of 1966. R code to reproduce our results is available atgithub.com/egosv/TwoPhase_postGWAS.
Clinical Burkholderia pseudomallei isolates from Queensland carry diverse bimABm genes that are associated with central nervous system disease and are phylogenomically distinct from other Australian strains
Authors: Burnard Delaney , Bauer Michelle J , Falconer Caitlin , Gassiep Ian , Norton Robert E , Paterson David L , Harris Patrick N A
Published: May 2021

Burkholderia pseudomallei is an environmental gram-negative bacterium that causes the disease melioidosis and is endemic in many countries of the Asia-Pacific region. In Australia, the mortality rate remains high at approximately 10%. The bacterium is almost exclusively found in the endemic region, which spans the Northern Territory, Western Australia and North Queensland. However, Queensland infections remain understudied compared to those of the Northern Territory. This pilot study aimed to assess the prevalence of central nervous system disease associated variant bimABm, identify circulating antimicrobial resistance mutations and genetically distinct strains from Queensland, via comparative genomics. From 76 clinical isolates, we identified the bimABm variant in 20 (26.3%) isolates and in 9 (45%) of the isolates with documented central nervous system infection (n=18). Explorative analysis suggests a significant association between isolates carrying the bimABm variant and central nervous system disease (OR 2.8, 95% CI 1.3-6.0, P=0.009) compared with isolates carrying the wildtype bimABp, with the possibility of additional driving factors. Furthermore, 50% of isolates were identified as novel multi-locus sequence types (STs), while the bimABm variant was more commonly identified in isolates with novel sequence STs, compared to those of previously described STs. Additionally, mutations associated with acquired antimicrobial resistance were only identified in 14.5% of all genomes. The findings of this research have provided clinically relevant genomic data of B. pseudomallei in Queensland and suggest that the bimABm variant may enable risk stratification for the development CNS complications and be a potential therapeutic target.
A multimodal biomarker predicts dissemination of bronchial carcinoid
Authors: Reuling E.M.B.P. , Naves D.D. , Thunnissen E. , Kortman P.C. , Broeckaert M.A.M.B. , Plaisier P.W. , Dickhoff C. , Daniels J.M.A. , Radonic T.
Published: May 2021

Introduction

The extensive loss of lung parenchyma is a drawback of anatomical resection in bronchial carcinoids. Endobronchial therapy (EBT) has emerged as a safe and effective minimally invasive tissue sparing alternative for small intraluminal tumors. Currently, therapeutic decision making in patients with bronchial carcinoid is mainly based on tumor morphology and patient characteristics. The availability of more accurate biomarkers might help clinicians in selecting low-risk tumors for EBT. Therefore, we investigated radiological (tumor diameter), morphometric (mitotic index) and immunohistochemical (OTP, CD44, Ki-67, Rb and P16) markers as predictors of dissemination.

Material and methods

Patients referred to Amsterdam University Medical Centers with available histology were included. Clinical and morphological characteristics relevant for classification such as tumor diameter, mitotic count (MAI) and prognostic immunohistochemical markers as Ki-67, P16, Rb, Orthopedia homebox (OTP) and CD44 were analyzed.

Results

In a cohort of 171 patients, the vast majority were curatively treated with either EBT (n=61, 36%) or surgery (n=103, 60%). Seven (4%) patients presented with distant metastases at diagnosis. TC was diagnosed in 112 (65%) and AC in 59 (35%) patients. Nine (15%) patients treated with EBT had a local recurrence of disease during follow up and none developed lymph node or distant metastasis. Of all surgically treated patients, 13 (13%) had level 1 or 2 lymph node metastases. Additional 13 (13%) patients developed distant metastases, 11 (85%) were AC and 2 (15%) TC. Patients with tumor stage IA (tumor diameter ≤1cm) irrespective of tumor classification or immunohistochemical results did not develop distant metastases. Patients with typical carcinoid (<2 mitoses per 2 mm2) stage ≥IB with Ki67 <5% and positive CD44 did not develop distant metastases either. All patients with atypical carcinoid (≥2 mitoses 2 mm2), Ki-67 of ≥5% (p=<0.000) and loss of CD44 (p=<0.0001) developed distant metastases. Tumors with stage ≥IB and either ≥2 mitoses, Ki-67 >5% or loss of CD44 metastasized occasionally (11%).

Conclusion

Adding tumor diameter, CD44 and Ki-67 to the widely used TC/AC classification, provides a multimodal biomarker that better stratifies patients in prognostically favorable and unfavorable categories than current standards. These findings enable risk stratification allowing a tailored treatment approach for patients with bronchial carcinoid.
Comparative and systems analyses of Leishmania spp. non-coding RNAs through developmental stages
Authors: Martinez-Hernandez J. Eduardo , Aliaga-Tobar Victor , González Carolina , Monte-Neto Rubens , Martin Alberto J. M. , Maracaja-Coutinho Vinicius
Published: May 2021

Leishmania spp. is the etiological agent of leishmaniases, neglected diseases that seek to be eradicated in the coming years. The life cycle of these parasites involve different host and stress environments. In recent years, many studies have shown that several protein coding genes are directly involved with the development and host interactions, however, little is still known about the role of ncRNAs in life cycle progression. In this study, we aimed to identify the genomic structure and function of ncRNAs from Leishmania spp. and to get insights into the RNAome of this protozoan genus. We studied 26 strains corresponding to 16 different species of Leishmania. Our RNAome analysis revealed the presence of several ncRNAs that are shared through different species, allowing us to differentiate between subgenus as well as species that are canonically related to visceral leishmaniasis. We also studied co-expression relationships between coding genes and ncRNAs which in the amastigote developmental stage for Leishmania braziliensis and L. donovani revealed the presence of miRNA-like co-expressed with several coding genes involved in starvation, survival and histone modification. This work constitutes the first effort to characterize the Leishmania RNAome, supporting further approaches to better understand the role of ncRNAs in the gene regulation, infective process and host-parasite interaction.