bluuebunny/crossref_metadata_2025 huggingface dataset:
Spinal Fusion in Pediatric Patients With Low Bone Density: Defining the Value of DXA
Authors: Cohen Lara L. , Berry Jay G. , Ma Nina S. , Cook Danielle L. , Hedequist Daniel J. , Karlin Lawrence I. , Emans John B. , Hresko Michael Timothy , Snyder Brian D. , Glotzbecker Michael P.
Published: May 2022

Background:

Children with medical complexity are at increased risk of low bone mineral density (BMD) and complications after spinal fusion compared with idiopathic scoliosis patients. Our aim was to compare treatments and outcomes of children with medical complexity undergoing spinal fusion in those who had dual-energy x-ray absorptiometry (DXA) scans versus those who did not in an effort to standardize the workup of these patients before undergoing spinal surgery.

Methods:

We conducted a retrospective review of patients with low BMD who underwent spinal fusion at a tertiary care pediatric hospital between 2004 and 2016. We consulted with a pediatric endocrinologist to create standard definitions for low BMD to classify each subject. Regardless of DXA status, all patients were given a clinical diagnosis of osteoporosis [at least 2 long bone or 1 vertebral pathologic fracture(s)], osteopenia (stated on radiograph or by the physician), or clinically low bone density belonging to neither category. The last classification was used for patients whose clinicians had documented low bone density not meeting the criteria for osteoporosis or osteopenia. Fifty-nine patients met the criteria, and 314 were excluded for insufficient follow-up and/or not meeting a diagnosis definition. BMD Z-scores compare bone density ascertained by DXA to an age-matched and sex-matched average. Patients who had a DXA scan were also given a DXA diagnosis of low bone density (≤−2 SD), slightly low bone density (−1.0 to −1.9 SD), or neither (>−1.0 SD) based on the lowest BMD Z-score recorded.

Results:

Fifty-nine patients were analyzed. Fifty-four percent had at least 1 DXA scan preoperatively. Eighty-one percent of DXA patients received some form of treatment compared with 52% of non-DXA patients (P=0.03).

Conclusions:

Patients referred for DXA scans were more likely to be treated for low BMD, although there is no standardized system in place to determine which patients should get scans. Our research highlights the need to implement clinical protocols to optimize bone health preoperatively.

Level of Evidence:

Level II—retrospective prognostic study.
Extracorporeal Immunomodulation Treatment and Clinical Outcomes in ICU COVID-19 Patients
Authors: Yessayan Lenar T. , Neyra Javier A. , Westover Angela J. , Szamosfalvi Balazs , Humes H. David
Published: May 2022

OBJECTIVES:

To evaluate safety and clinical outcomes of extracorporeal immunomodulation treatment with a selective cytopheretic device (SCD) in COVID-19 ICU patients with multiple organ failure.

DESIGN:

Two-center, prospective, single-arm treatment clinical trial.

SETTING:

ICUs at two academic medical centers between September 2020 and July 2021.

PATIENTS:

Twenty-two COVID-10 patients in the ICU with acute respiratory distress syndrome who required mechanical ventilation. Nearly all included patients in the intervention group except one had acute kidney injury requiring continuous renal replacement therapy (CRRT). Sixteen subjects meeting enrollment criteria were selected as contemporaneous controls from a concurrent prospective registry CRRT trial.

INTERVENTION:

Treatment with an SCD integrated into a continuous renal replacement extracorporeal blood circuit for up to 10 days to provide autologous leukocyte cell processing to immunomodulate the hyperinflammatory disease state of COVID-19.

MEASUREMENTS AND MAIN RESULTS:

SCD treatment in COVID-19 ICU patients with multiple organ failure demonstrated an acceptable safety profile with no device-related serious adverse events. Treatment of these patients resulted in the selective removal of highly activated circulating leukocytes as determined by flow cytometry. Significant reductions were observed in the elevated plasma levels of eight cytokines and biomarkers, including interleukin (IL)6, IL15, IL10, and soluble ST2, which are predictive of mortality in COVID-19 patients. Significant improvements of leukocytosis and Po
2/Fio
2 ratios occurred during treatment not observed in the control group. SCD-treated subjects had a reduction in 60-day mortality of 50% compared with 81% in the control cohort. The subjects who received greater than 96 hours of SCD treatment, per protocol, had a further reduction in mortality to 31% (p < 0.012).

CONCLUSIONS:

Extracorporeal immunomodulation therapy with an SCD demonstrated safety without any device-related serious adverse events. As a rescue therapy in COVID-19 ICU patients progressing to multiple organ failure despite maximal pharmacologic and organ support interventions, SCD treatment resulted in improved clinical outcomes. This autologous leukocyte cell processing technology may provide a new approach in the treatment of unremitting hyperinflammation of COVID-19.
Brachial Plexus Birth Injury: Trends in Early Surgical Intervention over the Last Three Decades
Authors: Wells Matthew E. , Tihista Mikel C. , Diamond Shawn
Published: May 2022

Background:

Early surgical management of brachial plexus birth injury has advanced owing to targeted surgical techniques and increases in specialty-centers and multi-institutional collaboration. This study seeks to determine trends in the early surgical management of BPBI over the last 30 years.

Methods:

A systematic review was performed through MEDLINE (PubMed) identifying studies limited to the early surgical management of BPBI from 1990 to current. Patients treated after 1 year of age (ie, tendon transfers and secondary reconstructive efforts) were excluded. Diagnostic tests, age of intervention, surgical treatment modalities, and outcome scoring systems were extrapolated and compared so as to determine trends in management over time.

Results:

Seventeen studies met criteria, summating a total of 883 patients. The most commonly reported physical examination classifications were the Mallet and AMS scoring systems. Most patients underwent neuroma excision and sural nerve autografting (n = 618, 70%) when compared with primary nerve transfers (148, 16.8%), primary nerve transfer with autografting combinations (59, 6.7%), or neurolysis alone (58, 6.6%). There was no significant change in the proportion of patients treated with sural nerve grafting, combination graft and transfer procedures, or isolated neurolysis over time. However, there has been a significant increase in the proportion of patients treated with primary nerve transfer procedures (τ
b = 0.668, P < 0.01) over time.

Conclusion:

Although neuroma excision and sural nerve autografting has been the historic gold-standard treatment for brachial plexus birth injury, peripheral nerve transfers have become increasingly utilized for surgical management.
Perspectives About Transition Readiness Among Adolescents and Young People Living With Perinatally Acquired HIV in Rural, Southwestern Uganda: A Qualitative Study
Authors: Ashaba Scholastic , Zanoni Brian C. , Baguma Charles , Tushemereirwe Patricia , Nuwagaba Gabriel , Nansera Denis , Maling Samuel , Tsai Alexander C.
Published: May 2022

Despite the availability of antiretroviral therapy, treatment outcomes are worse among adolescents and young adults living with perinatally acquired HIV (AYLPHIV). These disparities are magnified during the transition from pediatric to adult-based HIV care. We conducted in-depth interviews with AYLPHIV aged 15–24 years (n = 30), their caregivers (n = 10), and health care providers (n = 10). All participants provided written assent and/or informed consent to enroll. Thematic content analysis was used to identify and analyze themes relevant to transition readiness. We grouped perspectives on transition readiness into 4 themes: preparation for transition, communication between stakeholders, social support, and timing of transition. AYLPHIV in sub-Saharan Africa who are facing a transition to adult HIV care should be equipped with relevant information about their illness, self-advocacy skills, and support from caregivers and health care providers to remain engaged in HIV care.
Prosthetic and orthotic students' perceptions on online courses during the COVID-19 pandemic in Japan
Authors: Aduayom-Ahego Akouetevi , Arayama Motohide , Ehara Yoshihiro
Published: May 2022

Background:

The effects of the novel coronavirus (COVID-19) pandemic have changed both the traditional teaching methods and clinical placements.

Objectives:

To investigate the effects of COVID-19 on the prosthetics and orthotics (P&O) training program in Japan.

Study design:

A cross-sectional national survey.

Methods:

A Google form survey was distributed to students through the heads of the department of P&O program across Japan. Descriptive statistics were used to analyze the data.

Results:

One hundred sixty-six students (107 males and 59 females) responded to the survey. The respondents' grades were as follows: freshman, 22.3% (n = 37); sophomore, 33.7% (n = 56); junior, 27.1% (n = 45); and senior, 16.9% (n = 28). Forty-seven percent (n = 78) reported that their clinical placements have been cancelled because of the COVID-19 pandemic. Only 15.1% (n = 25) have performed their clinical placements during the pandemic. Regarding career preparation, 16.3% (n = 27) had face-to-face interviews and 10.2% (n = 17) have reported being interviewed online. Of a total of 44 respondents who were interviewed for jobs in P&O industries and rehabilitation centers, 79.5% (n = 35) job appointments have been cancelled and 15.9% (n = 7) postponed.

Conclusions:

The event of the COVID-19 pandemic has proved necessary to renew the traditional teaching and learning model in colleges worldwide. Most students have been affected by clinical placements and career preparation. Therefore, promoting telehealth in the existing rehabilitation facilities and P&O industries to provide services might be an alternative method to address students' clinical placements in similar life condition events.
FDG PET/CT in Prostate Metastasis From Gastric Cancer
Authors: Ji Xia , Dong Aisheng
Published: May 2022

Prostate metastasis from gastric cancer is rare. We report MRI and FDG PET/CT findings in a case with prostate metastasis from gastric cancer. In this case, the prostate metastasis was the first manifestation of the gastric cancer. This case demonstrates the usefulness of FDG PET/CT in identifying the primary gastric cancer and its contribution for an accurate staging. Familiarity with the FDG PET/CT findings of the prostate metastasis may be useful for the differential diagnosis of the hypermetabolic prostate lesions.
Judicial Commission of the International Committee on Systematics of Prokaryotes: Minutes of the Meeting on 3 March 2022
Authors: Göker Markus
Published: May 2022

The minutes of the online meeting of the Judicial Commission of the International Committee on Systematics of Prokaryotes that was held on 3 March 2022 per video conference are presented.
Isolation of Exophiala dermatitidis is not associated with worse clinical outcomes during acute pulmonary exacerbations in cystic fibrosis
Authors: Tewkesbury Daniel H. , Looi Evelyn , Barry Peter J. , Edwards Gemma , Green Heather , Smith Matthew , Jones Andrew M.
Published: May 2022

Introduction. The black yeast Exophiala dermatitidis has been isolated in respiratory samples from people with cystic fibrosis (CF). However, adequate detection may require longer incubation periods than the current UK national standard for CF respiratory samples. Furthermore, it is unclear whether isolation of E. dermatitidis is associated with poorer clinical outcomes in CF.

Hypothesis/gap statement.
E. dermatitidis does not cause clinically significant lung disease in CF adults.

Aim. To evaluate differences in clinical outcomes over a 12 month period and during acute pulmonary exacerbations between CF adults with and without untreated E. dermatitidis.

Methodology. Incubation times for respiratory samples on Sabouraud dextrose agar with chloramphenicol (SABC) plates at a large regional adult CF centre were extended from 2 to 7 days over a 1 month period. The number of patients from whom E. dermatitidis was isolated, and the length of incubation time prior to isolation, were recorded. Outcomes of treatment of exacerbations with intravenous antibiotics but in the absence of concomitant antifungal therapy were compared between those with and without E. dermatitidis, as were changes in lung function and body mass index (BMI) over a 12 month period.

Results. Extended incubation unmasked the presence of E. dermatitidis in 22 of 132 patients; all isolations occurred after >48 h of incubation. Patients who isolated E. dermatitidis had lower rates of

Pseudomonas aeruginosa

isolation (P=0.02) and higher rates of non-tuberculous mycobacteria isolation (P=0.03), and were more likely to be prescribed a long-term antifungal medication (P=0.03), but had no differences in age, sex, baseline lung function or body mass index (BMI). There were no differences in response to treatment of acute exacerbations between patients with and without E. dermatitidis, or in change in forced expiratory volume in 1 s (FEV1), BMI and number of exacerbations over 12 months of follow-up.

Conclusion.
E. dermatitidis is not associated with worse clinical outcomes in CF. Given potential side effects and drug interactions, routine targeting of E. dermatitidis with antifungals during acute exacerbations is not advised.
Computational analysis of peripheral blood smears detects disease-associated cytomorphologies
Authors: de Almeida José Guilherme , Gudgin Emma , Besser Martin , Dunn William G. , Cooper Jonathan , Haferlach Torsten , Vassiliou George S. , Gerstung Moritz
Published: May 2022

Many hematological diseases are characterized by altered abundance and morphology of blood cells and their progenitors. Myelodysplastic syndromes (MDS), for example, are a type of blood cancer manifesting via a range of cytopenias and dysplastic changes of blood and bone marrow cells. While experts analyze cytomorphology to diagnose MDS, similar alterations can be observed in other conditions such as haematinic deficiency anemias, and definitive diagnosis requires complementary information such as blood counts, karyotype and molecular testing. However, recent works demonstrated that computational analysis of bone marrow slides predicts not only MDS or AML but also the presence of specific mutations. Here, we present and make available Haemorasis, a computational method that detects and characterizes white and red blood cells (WBC and RBC, respectively) in peripheral blood slides, and apply it to over 300 individuals with different conditions (SF3B1-mutant andSF3B1-wildtype MDS, megaloblastic anemia and iron deficiency anemia), where Haemorasis detects over half a million WBC and millions of RBC. We then show how these large sets of cell images can be used in diagnosis and prognosis, whilst identifying novel associations between computational morphotypes and disease. We find that hypolobulated neutrophils and large RBC are characteristic ofSF3B1-mutant MDS, and, while prevalent in both iron deficiency and megaloblastic anemia, hyperlobulated neutrophils are larger in the latter. Finally, we externally validate these methods, showing they generalize to other centers and scanners.
Do Some Super-Spreaders Spread Better? Effects of individual heterogeneity in epidemiological traits
Authors: Beagle Alexis S. , Budischak Sarah A. , Craft Meggan E. , Forbes Kristian , Hall Richard , Nguyen David , Cressler Clay E.
Published: May 2022

Many high-profile outbreaks are driven by super-spreading, including HIV, MERS, Ebola, and the SARS-Cov-2 pandemic. That super-spreading is a common feature of epidemics is immutable, however, the relative importance of 2super-spreaders to the outcome of an epidemic, and the individual-level traits that lead to super-spreading, is less clear. For example, an individual may contribute disproportionately to transmission by way of an extremely high contact rate or by way of low recovery, but how these two super-spreaders differ in their effect on epidemiological dynamics is unclear. Furthermore, epidemiological traits may often covary with one another in ways that promote or inhibit super-spreading. What patterns of covariation, and between what traits, are most likely to lead to large epidemics driven by super-spreading? Using stochastic individual-based simulations of an SIR epidemiological model, we explore how variation and covariation between transmission-related traits (contact rate and infectiousness) and duration-related traits (virulence and recovery) of infected individuals affects super-spreading and peak epidemic size. We show that covariation matters when contact rate and infectiousness covary: peak epidemic size is largest when they covary positively and smallest when they covary negatively. We did not see that more super-spreading always leads to larger epidemics, rather, we show that the relationship between super-spreading and peak epidemic size is dependent on which traits are covarying. This suggests that there may not necessarily be any general relationship between the frequency of super-spreading and the size of an epidemic.
Whole-Genome Sequencing Of Omicron Identified Multiple Outbreaks And Introduction Events In India During November 2021 and January 2022
Authors: Marathe Shreedhanya D , Shamanna Varun , Nagaraj Geetha , Nischita S , Bhaskaran Muthumeenakshi , Ravikumar K L
Published: May 2022

The variant of Concern(VOC), Omicron is the predominant variant circulating throughout the world of the SARS COV2 pandemic during the third wave including India. The World Health Organisation has designated this highly mutated variant as a VOC due to its high transmissibility and risk of reinfection. Whole-genome sequencing and analysis were performed for SARS-CoV2 PCR positive samples between Dec21 to Jan22. From the 133 omicron variants detected, genomic analysis was carried out by contextualizing them with 1586 complete genomes of Omicron from India obtained from GISAID.

The Omicron variant prevalence in India has increased in a log phase within 3 months in most of the metropolitan cities. The sublineage BA.1 was first observed in the country, while the BA.2 sublineage was introduced to Delhi in the mid of December 2021. The two outbreaks observed were of BA.2 variant and were observed to spread to multiple cities in a short time. The rapid spread and specific mutations in the outbreak samples of Omicron indicate that the variant is highly transmissible when compared to previous variants. The study shows the importance of genomic sequence to identify the emergence of clusters and take actions to prevent further spreading events.
Genetic variations inEIF2AK3are associated with neurocognitive impairment in people living with HIV
Authors: Akay-Espinoza Cagla , Bond Sarah , Dombroski Beth A. , Kallianpur Asha , Bharti Ajay , Franklin Donald R. , Schellenberg Gerard D. , Heaton Robert K. , Grant Igor , Ellis Ronald J. , Letendre Scott L. , Jordan-Sciutto Kelly L.
Published: May 2022

Coding and noncoding single-nucleotide variants (SNVs) ofEIF2AK3, which encodes an integrated stress response (ISR) kinase, may play a role in neurodegenerative disorders. We used a candidate gene approach to determine the correlation ofEIF2AK3SNVs with neurocognitive (NC) impairment (NCI), which can persist with viral suppression from antiretroviral therapy (ART) in people with HIV (PWH). This retrospective study of prospectively collected data included participants of the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) cohort, after excluding participants with severe neuropsychiatric comorbidities. Genome-wide data previously obtained in the CHARTER cohort participants (n=1,047) were analyzed to interrogate the association of three noncodingEIF2AK3SNVs with the continuous global deficit score (GDS) and global NCI (GDS≥0.5). Targeted sequencing (TS) was performed in 992 participants with available genomic DNA to determine the association of three codingEIF2AK3SNVs with GDS and NCI. Analyses included univariable and multivariable methods such as analysis of variance and regression. Multivariable models covaried demographic, disease-associated, and treatment characteristics. The cohort characteristics were as follows: median age, 43.1 years; females, 22.8%; European ancestry, 41%; median CD4+ T cell counts, 175/µL (nadir) and 428/µL (current). At first assessment, 70.5% used ART and 68.3% of these had plasma HIV RNA ≤ 200 copies/mL. A minority of participants had at least one risk allele for rs6739095 (T,41.7%), rs1913671 (C,41.4%), and rs11684404 (C,39.4%). All three noncodingEIF2AK3SNVs were associated with significantly worse GDS and more NCI (allp<0.05). By TS, fewer participants had at least one risk allele for rs1805165 (G,30.9%), rs867529 (G,30.9%), and rs13045 (A,41.2%). Homozygosity for all three coding SNVs was associated with significantly worse GDS and more NCI (allp<0.001). By multivariable analysis, the rs13045 A risk allele, current ART use, and Beck Depression Inventory-II (BDI) > 13 were independently associated with GDS and NCI (p<0.001). The other two coding SNVs did not significantly correlate with GDS or NCI after including rs13045 in the model. The codingEIF2AK3SNVs were specifically associated with worse performance in executive functioning, motor functioning, learning, and verbal fluency. Coding and non-coding SNVs ofEIF2AK3were associated with global NC and domain-specific performance. The effects were small-to-medium in size but were present in multivariable analyses. Specific SNVs inEIF2AK3may be an important component of genetic vulnerability to NC complications in PWH. Identification of host factors that predict NCI could allow for earlier interventions, including those directly modulating the ISR, to improve NC outcomes.
Safety, tolerability and immunogenicity of Biological E’s CORBEVAX™ vaccine in children and adolescents: A Prospective, Randomised, Double-blind, Placebo controlled, Phase-2/3 Study
Authors: Thuluva Subhash , Paradkar Vikram , Gunneri SubbaReddy , Yerroju Vijay , Mogulla Rammohan , Suneetha Pothakamuri Venkata , Turaga Kishore , Kyasani Mahesh , Manoharan Senthil Kumar , Adabala Srikanth , Javvadi Aditya Sri , Medigeshi Guruprasad , Singh Janmejay , Shaman Heena , Binayke Akshay , Zaheer Aymaan , Awasthi Amit , Narang Manish , Nanjappa Pradeep , Mahantshetti Niranjana , Garg Bishan Swarup , Ravi Mandal Ravindra Nath
Published: May 2022

Background

After establishing safety and immunogenicity of Biological E’s CORBEVAX™ vaccine in adult population (18-80 years) in Phase 1-3 studies, vaccine is further tested in children and adolescents in this study.

Methods

This is a phase-2/3 prospective, randomised, double-blind, placebo controlled, study evaluating safety, reactogenicity, tolerability and immunogenicity of CORBEVAX™ vaccine in children and adolescents of either gender between <18 to ≥12 years of age in Phase-II and <18 to ≥5 years of age in Phase-III with placebo as a control. This study has two age sub groups; age subgroup-1 with subjects <18 to ≥12 years of age and age subgroup-2 with subjects <12 to ≥5 years of age. In both age sub groups eligible subjects (SARS-CoV-2 RT-PCR negative and seronegative at baseline) were randomized to receive either CORBEVAX™ vaccine or Placebo in 3: 1 ratio.

Findings

The safety profile of CORBEVAX™ vaccine in both pediatric cohorts was comparable to the placebo control group. Majority of reported adverse events (AEs) were mild in nature. No severe or serious AEs, medically attended AEs (MAAEs) or AEs of special interest (AESI) were reported during the study period and all the reported AEs resolved without any sequelae. In both pediatric age groups, CORBEVAX™ vaccinated subjects showed significant improvement in humoral immune-responses in terms of anti-RBD-IgG concentrations, anti-RBD-IgG1 titers, neutralizing antibody (nAb)-titers against Ancestral Wuhan and Delta strains. Significantly high interferon gamma immune response (cellular) was elicited by CORBEVAX™ vaccinated subjects with minimal effect on IL-4 cytokine secretion.

Interpretations

The safety profile of CORBEVAX™ vaccine in <18 to ≥5 years’ children and adolescents was found to be safe and tolerable. The adverse event profile was also found to be acceptable. Significant increase in anti-RBD IgG and nAb titers and IFN-gamma immune responses were observed post vaccination in both pediatric age sub groups. Both humoral and cellular immune responses were found to be non-inferior to the immune responses induced by CORBEVAX™ vaccine in adult population. This study shows that CORBEVAX™ vaccine is highly immunogenic and can be safely administered to pediatric population as young as 5 years old.

The study was prospectively registered with clinical trial registry of India-CTRI/2021/10/037066
DBS for substance use disorders? An exploratory qualitative study of perspectives of people currently in treatment
Authors: Versalovic Erika , Klein Eran , Goering Sara , Ngo Quyen , Gliske Kate , Boulicault Marion , Sullivan Laura Specker , Thomas Mark J , Widge Alik S
Published: May 2022

Objective

While previous studies have discussed the promise of deep brain stimulation (DBS) as a possible treatment for substance use disorders (SUDs) and collected researcher perspectives on possible ethical issues surrounding it, none have consulted those with SUDs themselves. We addressed this gap by interviewing those with SUDs.

Methods

Participants viewed a short video introducing DBS, followed by a 1.5 hour semi-structured interview on their experiences with SUDs and their perspective on DBS as a possible treatment option. Interviews were analyzed by multiple coders who iteratively identified salient themes.

Results

We interviewed 20 people in 12-step based, inpatient treatment programs (10 [50%] white/Caucasian, 7 Black/African American [35%], 2 Asian [10%], 1 Hispanic/Latino [5%], and 1 [5%] Alaska Native/American Indian; 11 [45%] women). Interviewees described a variety of barriers they currently faced through the course of their disease that mirrored barriers often associated with DBS (stigma, invasiveness, maintenance burdens, privacy risks) and thus made them more open to the possibility of DBS as a future treatment option.

Conclusions

Individuals with SUDs gave relatively less weight to surgical risks and clinical burdens associated with DBS than previous surveys of provider attitudes anticipated. These differences derived largely from their experiences living with an often-fatal disease and encountering limitations of current treatment options. These findings support the study of DBS as a treatment option for SUDs, with extensive input from people with SUDs and advocates.
Seasonal patterns of SARS-CoV-2 transmission in secondary schools: a modelling study
Authors: Pham Thi Mui , Westerhof Ilse , Bootsma Martin C.J. , Kretzschmar Mirjam E. , Rozhnova Ganna , Bruijning-Verhagen Patricia
Published: May 2022

Background

The Omicron variant has caused a new wave of SARS-CoV-2 infections worldwide. We explore crucial epidemiological parameters driving seasonal patterns of SARS-CoV-2 transmission in secondary schools and assess various infection control interventions over a 2.5-year time frame.

Methods

We developed an agent-based model parameterised with data from secondary schools in the Netherlands. We modelled the circulation of Omicron assuming a stable introduction rate of infections and accounted for uncertainty in epidemiological parameters describing virus transmissibility, susceptibility to reinfection, vaccine immune escape, and waning of sterilising immunity. We quantified the SARS-CoV-2 health burden defined as number of symptomatic student days. We further evaluated the cost-benefit (number of prevented infected students per absent student) for reactive quarantine interventions, regular screening using antigen tests, and annual booster vaccinations.

Findings

Durability of sterilising immunity is a key parameter that governs temporal SARS-CoV-2 transmission patterns in secondary schools. Our model predicts pronounced within-school seasonal patterns with dominant autumn outbreaks and smaller winter outbreaks and a maximum prevalence of 2.9% (95% CI: 0.7%-6.6%) symptomatic students during infection peaks. Regular screening and annual booster vaccination may reduce the health burden up to 15% (95% CI: 1.5%-27.8%) and have a higher cost-benefit ratio than reactive quarantine interventions (reduction: 4.3%; 95% CI: -10.1% to 17.6%).

Interpretation

Immunity waning will determine the intensity and pattern of SARS-CoV-2 transmission in secondary schools in the medium-term future. If mitigation strategies are needed, screening and annual booster vaccination have the highest cost-benefit by reducing viral transmission with little educational disruption.
Global burden of mental health problems among children and adolescents during COVID-19 pandemic: A systematic umbrella review
Authors: Hossain M. Mahbub , Nesa Fazilatun , Das Jyoti , Aggad Roaa , Tasnim Samia , Bairwa Mohan , Ma Ping , Ramirez Gilbert
Published: May 2022

Mental health problems among children and adolescents are increasingly reported amidst the coronavirus disease (COVID-19) pandemic. In this umbrella review, we aimed to synthesize global evidence on the epidemiologic burden and correlates of child and adolescent mental health (CAMH) problems during this pandemic from existing systematic reviews and meta-analyses. We evaluated 422 citations and identified 17 eligible reviews on the epidemiology of CAMH in the context of COVID-19. Most of the reviews reported a high prevalence of anxiety, depression, sleep disorders, suicidal behavior, stress-related disorders, attention-deficit/hyperactivity disorder, and other mental health problems. Also, factors associated with CAMH such as age, gender, place of residence, educational attainment, household income, sedentary lifestyle, social media and internet use, comorbidities, family relationships, parents’ psychosocial conditions, COVID-19 related experiences, closure of schools, online learning, and social support were reported across reviews. As most studies were cross-sectional and used nonrepresentative samples, future research on representative samples adopting longitudinal and intervention designs is needed. Lastly, multipronged psychosocial care services, policies, and programs are needed to alleviate the burden of CAMH problems during and after this pandemic.
Monitoring One Heart to Help Two: Heart Rate Variability and Resting Heart Rate using Wearable Technology in Active Women Across the Perinatal Period
Authors: Rowan Shon P. , Lilly Christa L. , Claydon Elizabeth A. , Wallace Jenna , Merryman Karen
Published: May 2022

BACKGROUND

Characterizing normal heart rate variability (HRV) and resting heart rate (RHR) in healthy women over the course of a pregnancy allows for further investigation into disease states, as pregnancy is the ideal time period for these explorations due to known decreases in cardiovascular health. To our knowledge, this is the first study to continuously monitor HRV and RHR using wearable technology in healthy pregnant women.

METHODS

A total of eighteen healthy women participated in a prospective cohort study of HRV and RHR while wearing a WHOOP® strap prior to conception, throughout pregnancy, and into postpartum. The study lasted from March 2019 to July 2021; data were analyzed using linear mixed models with splines for non-linear trends.

RESULTS

Eighteen women were followed for an average of 405.8 days (SD=153). Minutes of logged daily activity decreased from 28 minutes pre-pregnancy to 14 minutes by third trimester. A steady decrease in daily HRV and increase in daily RHR were generally seen during pregnancy (HRV Est. = -0.10, P<0.0001; RHR Est. = 0.05, P<0.0001). The effect was moderated by activity minutes for both HRV and RHR. However, at 49 days prior to birth there was a reversal of these indices with a steady increase in daily HRV (Est.=0.38, P< 0.0001) and decrease in daily RHR (Est. = -0.23, P< 0.0001), regardless of activity level, that continued into the postpartum period.

CONCLUSIONS

In healthy women, there were significant changes to HRV and RHR throughout pregnancy, including a rapid improvement in cardiovascular health prior to birth that was not otherwise known. Physical activity minutes of any type moderated the known negative consequences of pregnancy on cardiovascular health. By establishing normal changes using daily data, future research can now evaluate disease states as well as physical activity interventions during pregnancy and their impact on cardiovascular fitness.
Shared N417-dependent epitope on the SARS-CoV-2 Omicron, Beta and Delta-plus variants
Authors: Moyo-Gwete Thandeka , Madzivhandila Mashudu , Mkhize Nonhlanhla N , Kgagudi Prudence , Ayres Frances , Lambson Bronwen E , Manamela Nelia P , Richardson Simone I , Makhado Zanele , van der Mescht Mieke A , de Beer Zelda , de Villiers Talita Roma , Burgers Wendy A , Ntusi Ntobeko A B , Rossouw Theresa , Ueckermann Veronica , Boswell Michael T , Moore Penny L
Published: May 2022

As SARS-CoV-2 continues to evolve, several variants of concern (VOCs) have arisen which are defined by multiple mutations in their spike proteins. These VOCs have shown variable escape from antibody responses, and have been shown to trigger qualitatively different antibody responses during infection. By studying plasma from individuals infected with either the original D614G, Beta or Delta variants, we show that the Beta and Delta variants elicit antibody responses that are overall more cross-reactive than those triggered by D614G. Patterns of cross-reactivity varied, and the Beta and Delta variants did not elicit cross-reactive responses to each other. However, Beta-elicited plasma was highly cross-reactive against Delta plus (Delta+) which differs from Delta by a single K417N mutation in the receptor binding domain, suggesting the plasma response targets the N417 residue. To probe this further, we isolated monoclonal antibodies from a Beta-infected individual with plasma responses against Beta, Delta+ and Omicron, which all possess the N417 residue. We isolated a N417-dependent antibody, 084-7D, which showed similar neutralization breadth to the plasma. The 084-7D mAb utilized the IGHV3-23*01 germline gene and had similar somatic hypermutations compared to previously described public antibodies which target the 417 residue. Thus, we have identified a novel antibody which targets a shared epitope found on three distinct VOCs, enabling their cross-neutralization. Understanding antibodies targetting escape mutations such as K417N, which repeatedly emerge through convergent evolution in SARS-CoV-2 variants, may aid in the development of next-generation antibody therapeutics and vaccines.

Importance

The evolution of SARS-CoV-2 has resulted in variants of concern (VOCs) with distinct spike mutations conferring varying immune escape profiles. These variable mutations also influence the cross-reactivity of the antibody response mounted by individuals infected with each of these variants. This study sought to understand the antibody responses elicited by different SARS-CoV-2 variants, and to define shared epitopes. We show that Beta and Delta infection resulted in antibody responses that were more cross-reactive compared to the original D614G variant, but each with differing patterns of cross-reactivity. We further isolated an antibody from Beta infection, which targeted the N417 site, enabling cross-neutralization of Beta, Delta+ and Omicron, all of which possess this residue. The discovery of antibodies which target escape mutations common to multiple variants highlights conserved epitopes to target in future vaccines and therapeutics.
Long-COVID post-viral chronic fatigue syndrome and affective symptoms are associated with oxidative damage, lowered antioxidant defenses and inflammation: a proof of concept and mechanism study
Authors: Al-Hakeim Hussein Kadhem , Al-Rubaye Haneen Tahseen , Al-Hadrawi Dhurgham Shihab , Almulla Abbas F. , Maes Michael
Published: May 2022

The immune-inflammatory response during the acute phase of COVID-19, as assessed using peak body temperature (PBT) and peripheral oxygen saturation (SpO2), predicts the severity of chronic fatigue, depression and anxiety (“physio-affective”) symptoms three to four months later. The present study was performed to characterize whether the effects of SpO2 and PBT on the physio-affective phenome of Long COVID are mediated by immune, oxidative and nitrosative stress (IO&NS) pathways. This study assayed SpO2 and PBT during acute COVID-19, and C-reactive protein (CRP), malondialdehyde (MDA), protein carbonyls (PCs), myeloperoxidase (MPO), nitric oxide (NO), zinc, and glutathione peroxidase (Gpx) in 120 Long COVID individuals and 36 controls. Cluster analysis showed that 31.7% of the Long COVID patients had severe abnormalities in SpO2, body temperature, increased oxidative toxicity (OSTOX) and lowered antioxidant defenses (ANTIOX), and increased total Hamilton Depression (HAMD) and Anxiety (HAMA) and Fibromylagia-Fatigue (FF) scores. Around 60% of the variance in the physio-affective phenome of Long COVID (a factor extracted from HAMD, HAMA and FF scores) was explained by OSTOX/ANTIOX ratio, PBT and SpO2. Increased PBT predicted increased CRP and lowered ANTIOX and zinc levels, while lowered SpO2 predicted lowered Gpx and increased NO production. Both PBT and SpO2 strongly predict OSTOX/ATIOX during Long COVID. In conclusion, the impact of acute COVID-19 on the physio-affective symptoms of Long COVID is partly mediated by OSTOX/ANTIOX, especially lowered Gpx and zinc, increased MPO and NO production and lipid peroxidation-associated aldehyde formation. Post-viral physio-affective symptoms have an inflammatory origin and are partly mediated by neuro-oxidative toxicity.
Supporting the revision of the health benefits package in Uganda: a constrained optimisation approach
Authors: Mohan Sakshi , Walker Simon , Sengooba Freddie , Kiracho Elizabeth Ekirapa , Mayora Chrispus , Ssennyonjo Aloysius , Aliti Candia Tom , Revill Paul
Published: May 2022

This study demonstrates how the linear constrained optimization approach can be used to design a health benefits package (HBP) which maximises the net disability adjusted life years (DALYs) averted given the health system constraints faced by a country, and how the approach can help assess the marginal value of relaxing health system constraints. In the analysis performed for Uganda, 58 interventions were included in the HBP in the base scenario, resulting in a total of 49.9 million net DALYs averted. When task shifting of pharmacists’ and nutrition officers’ tasks to nurses is allowed, 68 interventions were included in the HBP resulting in a total of 53.8 million net DALYs averted (a 7.8% increase). Further, investing only $39 towards hiring additional nutrition officers’ time could avert one net DALY; this increased to $55, $56, and $123 for nurses, pharmacists and doctors respectively, and $971 for expanding the consumable budget.
Asymptomatic carriage ofPlasmodium falciparumin children living in a hyperendemic area occurs independently of IgG responses but is associated with a balanced inflammatory cytokine ratio
Authors: Fogang Balotin , Schoenhals Matthieu , Maloba Franklin M. , Biabi Marie Florence , Essangui Estelle , Donkeu Christiane , Cheteug Glwadys , Kapen Marie , Keumoe Rodrigue , Kemleu Sylvie , Nsango Sandrine , Cornwall Douglas H. , Eboumbou Carole , Perraut Ronald , Megnekou Rosette , Lamb Tracey J. , Ayong Lawrence S.
Published: May 2022

Background

Asymptomatic carriage of infected red blood cells (iRBCs) can be prevalent in communities regardless of transmission patterns and can occur with infection of differentPlasmodiumspecies. Clinical immunity dampens the inflammatory responses leading to disease symptoms in malaria. The aim of this study was to define the immunological correlates of asymptomatic carriage ofP. falciparumin a highly exposed population.

Methods

142 asymptomaticPlasmodium-infected individuals greater than 2 years of age without fever (body temperature <37.5°C) were followed weekly for 10 weeks before being treated with artemisinin-based combination treatment (ACT). Plasma levels of 38 cytokines were measured at baseline by Luminex and the quantity and growth inhibitory activities of circulating parasite-reactive antibodies measured. ThePlasmodiumantigen tested includedP. falciparummerozoite extract (ME) and schizont extract (SE), and the recombinant proteins Erythrocyte binding antigen 175 (EBA-175) and merozoite surface protein 1 (MSP-119).

Results

Median levels of IgG againstP. falciparumEBA-175 and MSP-119at baseline were significantly higher in those older than 20 years of age compared with the younger age group and appeared to correlate with better parasite control. Amongst all participants there were no discernible changes in IgG levels over time. Parasite density was higher in the younger age group and associated with IL-10, TNF-α and MCP-1 levels. A balanced IL-10:TNF-α ratio was associated with asymptomatic malaria regardless of age, and balanced ratios of IL-10/TNF-α and IL-10/IFN-γ were the only significant correlate of maintenance of asymptomatic malaria over the course of the study in individuals 20 years of age and younger.

Conclusion

The above findings indicate that asymptomatic carriage ofP. falciparumin children living in a hyperendemic area occurs independently of IgG but is associated with a balanced inflammatory cytokine ratio.
Increased Prevalence of Rare Copy Number Variants in Treatment-Resistant Psychosis
Authors: Farrell Martilias , Dietterich Tyler E , Harner Matthew K , Bruno Lisa M , Filmyer Dawn M , Shaughnessy Rita A , Lichtenstein Maya L , Xavier Rose Mary , Britt Allison M , Biondi Tamara F , Crowley James J , Lázaro-Muñoz Gabriel , Forsingdal Annika E , Nielsen Jacob , Didriksen Michael , Berg Jonathan S , Wen Jia , Szatkiewicz Jin , Sullivan Patrick F , Josiassen Richard C
Published: May 2022

Background

It remains unknown why ∼30% of patients with psychotic disorders fail to respond to treatment. Previous genomic investigations into treatment-resistant psychosis have been inconclusive, but some evidence suggests a possible link between rare disease-associated copy number variants (CNVs) and worse clinical outcomes in schizophrenia. Here, we test whether schizophrenia-associated CNVs are more prevalent in patients with treatment-resistant psychotic symptoms compared to previously published schizophrenia cases not selected for treatment-resistance.

Methods

CNVs were identified using chromosomal microarrays and exome sequencing in 509 patients with treatment-resistant psychosis (a lack of clinical response to ≥ 3 adequate antipsychotic medication trials over at least five years of psychiatric hospitalization). Prevalence of schizophrenia-associated CNVs in this sample was compared against a previous large schizophrenia cohort study.

Results

In total, 47 cases (9.2%) carried at least one CNV with known or possible neuropsychiatric risk. The prevalence of schizophrenia-associated CNVs (n=21; 4.1%) was significantly increased compared to a previous schizophrenia cohort study (p = 0.005322; OR = 1.93). This increase in prevalence was primarily due to duplications at 15q11.2-q13.1 and 16p11.2, which were independently associated with treatment-resistance in pairwise loci-based analysis.

Conclusions

These findings suggest that rare schizophrenia-associated CNVs, particularly duplications of 15q11.2-q13.1 and 16p11.2, may serve as biological entry points for studying treatment resistance. Further investigation will be necessary to elucidate the spectrum of phenotypic characteristics observed in adult psychiatric patients with disease-associated CNVs.
Longitudinal analysis reveals elevation then sustained higher expression of autoantibodies for six months after SARS-CoV-2 infection
Authors: Bhadelia Nahid , Olson Alex , Smith Erika , Riefler Katherine , Cabrejas Jacob , Ayuso Maria-Jose , Clarke Katherine , Yuen Rachel R. , Lin Nina H. , Manickas-Hill Zachary J. , Rifkin Ian , Bujor Andreea , Sagar Manish , Belkina Anna C. , Snyder-Cappione Jennifer E.
Published: May 2022

High autoantibody levels are found in individuals hospitalized for COVID-19. The temporal trajectories and levels of these autoantibodies months into convalescence after SARS-CoV-2 infection are unclear. It is also unknown if the composite autoantibody signatures of convalescent SARS-CoV-2-infected individuals resemble those with diagnosed autoimmune diseases. We measured the circulating levels of 17 autoantibodies associated with autoimmune connective tissue diseases from SARS-CoV-2 hospitalized and outpatient participants, as well as from individuals with scleroderma (SSc), systemic lupus erythematosus (SLE), and uninfected pre-pandemic controls. Seven of the 17 autoantibodies measured were higher in hospitalized and/or outpatient SARS-CoV-2 individuals an average of six months after symptom onset compared with controls, with multivariate analyses revealing links between SARS-CoV-2 infection and positivity of SSB-La, Sm, Proteinase 3, Myleoperoxidase, Jo-1, and Ku reactive IgG six months post-symptom onset. Autoantibody levels from SARS-CoV-2 infected individuals were followed over time from initial symptom onset for an average of six months, and different temporal autoantibody trajectories were classified. A ‘negative, then positive’ expression pattern was found for at least one autoantibody in 18% of the outpatient and 53% of the hospitalized participants, indicating initiation and durable expression of self-reactive immune responses post-infection, particularly with severe acute illness. Analysis of individual participant autoantibody expression patterns revealed similar patterns between pre-pandemic and convalescent SARS-CoV-2 infected groups that are distinct from participants with both the SSc and SLE. As autoantibody positivity can occur years prior to autoimmune disease onset, the possibility that SARS-CoV-2-associated autoantibodies are a herald of future autoimmune disorders requires further investigation.

One Sentence Summary

Autoantibody levels rise after acute SARS-CoV-2 infection and remain elevated for at least six months after symptom onset in participants with mild or severe COVID-19.
Managing COVID-19 in an Australian designated isolation facility: Implications for current and future healthcare crises
Authors: Achat Helen M , Mittal Rakhi , Stubbs Joanne M , Gilroy Nicky , Schindeler Suzanne K , Shaban Ramon Z , Solano Thomas
Published: May 2022

Health care workers’ (HCWs) lived experiences and perceptions of the pandemic can prove to be a valuable resource in the face of a seemingly persistent Novel coronavirus disease 2019 (COVID-19) – to inform ongoing efforts, as well as identify components essential to a crisis preparedness plan and the issues pertinent to supporting relevant, immediate change. We employed a phenomenological approach and, using purposive sampling, conducted 39 semi-structured interviews with senior healthcare professionals who were employed at a designated COVID-19 facility in New South Wales (NSW), Australia during the height of the pandemic in 2020. Participants comprised administrators, heads of department and senior clinicians. We obtained these HCWs’ (i) perspectives of their lived experience on what was done well and what could have been done differently and (ii) recommendations on actions for current and future crisis response. Four themes encapsulated respondents’ insights that should inform our capacity to meet current needs, direct meaningful and in situ change, and prepare us for future crises. Respondents’ observations and recommendations are informative for decision-makers tasked with mobilising an efficacious approach to the next health crisis and, in the interim, would aid the governance of a more robust workforce to effect high quality patient care in a safe environment.