bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors Associated with Open Access Publishing Costs in Oncology Journals
Authors: Koong Alex , Gardner Ulysses G , Burton Jason , Stewart Caleb , Thompson Petria S , Fuller Clifton D , Ludmir Ethan B , Rooney Michael K
Published: May 2022

Background

Open access (OA) publishing represents an exciting opportunity to facilitate dissemination of scientific information to global audiences. However, OA publication is often associated with significant article processing charges (APCs) for authors, which may thus serve as a barrier to publication.

Methods

We identified oncology journals using the SCImago Journal & Country Rank database. All journals with an OA publication option and APC data openly available were included. We searched journal websites and tabulated journal characteristics, including APC amount (USD), OA model (hybrid vs full), 2-year impact factor (IF), H-index, number of citable documents, modality/treatment specific (if applicable), and continent of origin. We generated a multiple regression model to identify journal characteristics independently associated with OA APC amount.

Results

Of 367 oncology journals screened, 251 met final inclusion criteria. The median APC was 2957 USD (IQR 1958-3450). On univariable testing, journals with greater number of citable documents (p<0.001), higher IF (p < 0.001), higher H-index (p < 0.001), and those using the hybrid OA model (p < 0.001) or originating in Europe/North America (p < 0.001) tended to have higher APCs. In our multivariable model, number of citable documents, IF, OA publishing model, and region persisted as significant predictors of processing charges.

Conclusions

OA publication costs are greater in oncology journals that publish more citable articles, utilize the hybrid OA model, have higher IF, and are based in North America or Europe. These findings may inform targeted action to help the oncology community fully appreciate the benefits of open science.
Detection Of SARS-COV-2 Variants Of Concern In Wastewater Of Leuven, Belgium
Authors: Bloemen Mandy , Delang Leen , Rector Annabel , Raymenants Joren , Thibaut Jonathan , Pussig Bram , Fondu Lore , Aertgeerts Bert , Van Ranst Marc , Van Geet Chris , Arnout Jef , Wollants Elke
Published: May 2022

To investigate whether wastewater surveillance can be used as an early warning system to detect a rise in SARS-CoV-2 positive cases, and to follow the circulation of specific variants of concern (VOC) in particular geographical areas, wastewater samples were collected from local neighborhood sewers and from a large regional wastewater treatment plant (WWTP) in the area of Leuven, Belgium. In two residential sampling sites, a rise in viral SARS-CoV-2 copies in wastewater preceded the peaks in positive cases. In the WWTP, peaks in the wastewater viral load were seen simultaneous with the waves op positive cases caused by the original Wuhan SARS-CoV-2 strain, the Alpha variant and the Delta variant. For the Omicron BA.1 variant associated wave, the viral load in wastewater increased to a lesser degree, and much later than the increase in positive cases, which could be attributed to a lower level of fecal excretion, as measured in hospitalized patients. Circulation of SARS-CoV-2 VOCs (Alpha, Delta and Omicron) could be detected based on the presence of specific key mutations. The shift in variants was noticeable in the wastewater, with key mutations of two different variants being present simultaneously during the transition period.

We found that wastewater based surveillance is a sensitive tool to monitor SARS-CoV-2 circulation levels and VOCs in larger regions. This can prove to be highly valuable in times of reducing testing capacity. Differences in excretion levels of various SARS-CoV-2 variants should however be taken into account when using wastewater surveillance to monitor SARS-CoV-2 circulation levels in the population.
Elevated expression of RGS2 may underlie reduced olfaction in COVID-19 patients
Authors: Avnat Eden , Shapira Guy , Gurwitz David , Shomron Noam
Published: May 2022

Anosmia is common in COVID-19 patients, lasting for weeks or months following recovery. The biological mechanism underlying olfactory deficiency in COVID-19 does not involve direct damage to nasal olfactory neurons, which do not express the proteins required for SARS-CoV-2 infection. A recent study suggested that anosmia results from downregulation of olfactory receptors. We hypothesized that anosmia in COVID-19 may also reflect SARS-CoV-2 infection-driven elevated expression of regulator of G protein signaling 2 (RGS2), a key regulator odorant receptor, thereby silencing their signaling. To test our hypothesis, we analyzed gene expression of nasopharyngeal swabs from SARS-CoV-2 positive patients and non-infected controls (two published RNA-sequencing datasets, 580 individuals). Our analysis found upregulated RGS2 expression in SARS-CoV-2 positive patients (FC=14.5, Padj=1.69e-05 and FC=2.4; Padj=0.001, per dataset). Additionally, RGS2 expression was strongly correlated with PTGS2, IL1B, CXCL8, NAMPT and other inflammation markers with substantial upregulation in early infection. These observations suggest that upregulated expression of RGS2 may underlie anosmia in COVID-19 patients. As a regulator of numerous G-protein coupled receptors, RGS2 may drive further neurological symptoms of COVID-19. Studies are required for clarifying the cellular mechanisms by which SARS-CoV-2 infection drives the upregulation of RGS2 and other genes implicated in inflammation. Insights on these pathways may assist in understanding anosmia and additional neurological symptoms reported in COVID-19 patients.
“Sadly I think we are sort of still quite white, middle-class really” – Inequities in access to bereavement support: Findings from a mixed methods study
Authors: Selman L. E. , Sutton E. , Mirra R. Medeiros , Stone T. , Gilbert E. , Roulston Y. , Murray K. , Longo M. , Seddon K. , Penny A. , Mayland C.R. , Wakefield D. , Byrne A. , Harrop E.
Published: May 2022

Background

Voluntary and community sector bereavement services play are central to bereavement support in the UK.

Aim

To determine service providers’ perspectives on access to their support before and during the COVID-19 pandemic.

Design

Mixed methods study using an explanatory sequential design: (1) Cross-sectional online survey of UK bereavement services; (2) Qualitative interviews with staff and volunteers at case study services.

Settings/participants

147 services participated in the survey; 24 interviews were conducted across 14 services.

Results

67.3% of services reported there were groups with unmet needs not accessing their services before the pandemic; most frequently people from minoritised ethnic communities (49%), sexual minority groups (26.5%), deprived areas (24.5%) and men (23.8%). Compared with before the pandemic, 3.4% of services were seeing more people from minoritised ethnic groups, while 6.1% were seeing fewer. 25.2% of services did not collect ethnicity data. Qualitative findings demonstrated the disproportionate impact of the pandemic on minoritised ethnic communities, including disruption to care/mourning practices, and the need for culturally appropriate support. During the pandemic outreach activities were sometimes deprioritised; however, increased collaboration was also reported. Online provision improved access but excluded some. Positive interventions to increase equity included collecting client demographic data; improving outreach, language accessibility and staff representation; supporting other professionals to provide bereavement support; local collaboration and coproduction.

Conclusions

Service providers report inequities in access to bereavement support. Attention needs to be paid to identifying, assessing and meeting unmet needs for appropriate bereavement support. Identified positive interventions can inform service provision and research.
bp: Blood Pressure Analysis in R
Authors: Schwenck John , Punjabi Naresh M. , Gaynanova Irina
Published: May 2022

Despite the world-wide prevalence of hypertension, there is a lack in open-source software for analyzing blood pressure data. The R package bp fills this gap by providing functionality for blood pressure data processing, visualization, and feature extraction. In addition to the comprehensive functionality, the package includes six sample data sets covering continuous arterial pressure data (AP), home blood pressure monitoring data (HBPM) and ambulatory blood pressure monitoring data (ABPM), making it easier for researchers to get started. The R package bp is publicly available on CRAN and at https://github.com/johnschwenck/bp.
Susceptibility and characteristics of infections in patients with glucocorticoid excess or insufficiency: The ICARO tool
Authors: Minnetti Marianna , Hasenmajer Valeria , Sbardella Emilia , Angelini Francesco , Simeoli Chiara , Di Paola Nicola , Cozzolino Alessia , Pivonello Claudia , de Alcubierre Dario , Chiloiro Sabrina , Baldelli Roberto , De Marinis Laura , Pivonello Rosario , Pofi Riccardo , Isidori Andrea M.
Published: May 2022

Objective

Registry data show that Cushing’s syndrome (CS) and adrenal insufficiency (AI) increase mortality rates associated with infectious diseases. Little information is available on susceptibility to infections, especially milder forms that do not require hospitalization or prescription drugs. This study aimed to investigate infectious diseases in patients with glucocorticoid disorders through the development of a specific tool.

Methods

We developed and administered the ICARO questionnaire addressing infectious events over a 12-month observation period to 1017 outpatients referred to four University Hospitals between 2018 and 2019. The ICARO questionnaire showed good test-retest reliability. The odds of infection were estimated after adjustment for potential confounders and collated into the ICARO score, reflecting the frequency and duration of infections.

Results

75 patients were diagnosed with hypercortisolism and 135 with hypocortisolism; 237 were excluded for uncontrolled disease. The remaining 570 served as controls. Compared to controls, hypercortisolism was associated with higher odds of respiratory (2.3) and urinary tract infections (4.1), mycoses (3.3) and flu (2.1). Subgroup analysis confirmed an increased risk of UTI (3.7) and flu (3.2) in mild hypercortisolism. Post-dexamethasone cortisol levels correlated with the ICARO score. Hypocortisolism also exhibited higher odds of mycoses (2.3), gastrointestinal (2.2) and urinary tract infections (2.5), independently of any glucocorticoid replacement dose.

Conclusions

ICARO is the first of its kind questionnaire developed to address susceptibility to infections in patients with glucocorticoid disorders and revealed the high prevalence and features of self-reported infections. ICARO could be a valuable tool for monitoring infections in various clinical settings.
Time-of-Day Variation in Subjective Mood Among Lumosity Users
Authors: Mendoza Raymond A. , Fernandez Fabian-Xosé , Tubbs Andrew S. , Perlis Michael L. , Grandner Michael A.
Published: May 2022

Human mood varies according to both endogenous and situational factors. Analyzing patterns of online media engagement can provide additional insights into a third dimension of mood potentially involving time-of-day factors. Using data collected through the online brain-training app, Lumosity, we report real-world trends in mood expression among 500,000 respondents. Endorsements of positive mood by Lumosity gamers peaked midday, while endorsements of negative mood peaked overnight. These data suggest that there may be inherent bias towards negative mood when individuals are awake at night. More broadly, they suggest that internet data-trails have the potential to uncover fundamental aspects of human behavior.
Epidemiology of Door Crush Injuries- A retrospective cohort study of South Indian Population in a Tertiary care center
Authors: Krishnamoorthy Ashwin , Sethu Maithreyi , Viswanathan Singaravelu , Rajappa Srinivasan , Jayaram Sathishkumar
Published: May 2022

More than half of the fingertip injuries in children are due to door jamming injuries.1)2) There have been several studies on door crush injuries (DCI) but they pertain to either the paediatric age group or form a part of study of fingertip injuries in a large population. This article caters solely to studying the epidemiology, mechanism of injury, associated risk factors and suggests few simple techniques to avoid DCI.

Materials

Comparative analysis of the epidemiological data of all the patients with door crush injuries who presented to the Emergencies and the Out Patient Department in the Tertiary care centre was obtained from the MRD. This is a retrospective cohort study between January 2021 to December 2021. Patients with serious concomitant injuries, machine crush injury, heavy falling objects, window crush injury were excluded from the study.

Results

Of the 34 patients, 27 were male and 7 females. In 33 patients DCI was in the hinge side while only 1 had lock-side, entrance door being the commonest. 35% had first-aid done in a local nursing home before arriving at the hospital. 4 patients left against medical advice, 4 were conservatively treated and 2 had double finger injury. DCI was most common in preschool children. Right side and middle finger were most susceptible. 25% of the injuries happened on Mondays. Of the 36 fingers injured, 69% had pulp, 58% had nailbed and 22% had bony involvement. Primary suturing, local flap cover and K-wiring were the main modalities of treatment. Complications included altered sensation, nail deformity and contracture.

Conclusion

Door crush injury is a major contributor for finger crush injuries in both children and adults. Awareness among parents, the use of safety appliances to prevent accidental door closing, counselling by doctors and nurses greatly help to bring down the number of door crush injuries.
Assessment of the humoral response to the homologous Gam-COVID-Vac (Sputnik V) or heterologous Sputnik V/mRNA-1273 (Moderna) vaccination against SARS-CoV-2 in dialysis patients
Authors: Laham Gustavo , Martínez Alfredo P. , Gimenez Wanda Rojas , Amaya Lucas , Abib Anabel , Echegoyen Natalia , Díaz Carlos , Lucero Alicia , Martelli Antonella , Videla Cristina , Neukam Karin , Di Lello Federico A.
Published: May 2022

Introduction

The humoral response to vaccines is the most used tool to evaluate the protection against SARS-CoV-2 infection. Dialysis patients are a high-risk population and have a reduced immune response to vaccination.

Objective

To assess the humoral response to homologous Gam-COVID-Vac (Sputnik V) and heterologous Sputnik V/mRNA-1273 (Moderna) vaccination in dialysis patients.

Methods

SARS-CoV-2 anti-spike IgG (RBD) concentration was estimated 3-16 weeks after complete vaccination. Reactogenicity was evaluated until day 7 by patients’
s self-reported side events.

Results

107 participants were enrolled [n=84 homologous (SpV/SpV), n=23 heterologous (SpV/Mod)]. Median (IQR) age was 64 (50-75) years old and 79 (73.8%) were male. Additionally, 19 (22.6%) of the SpV/SpV and 4 (17.4%) of the SpV/Mod group had a prior confirmed SARS-CoV-2 infection (p=0.589). In the overall population, 103 patients reached seroconversion (96.3%). Anti-S-RBD IgG median titers (IQR) were higher in the heterologous [1222 (288-5680) BAU/mL] than in the homologous scheme [447 (100-1551) BAU/mL], p=0.022. In a linear model adjusted for age and gender, previous SARS-COV-2 infection (B: 1944.3; CI95: 1136.2-2753.4; p<0.001), and SpV/Mod vaccination scheme (B: 1241.5; CI95: 420.39-2062.6; p=0.003) were independently associated with anti-S-RBD levels. Finally, a higher frequency of adverse effects was associated with the heterologous scheme, although they were well tolerated by all individuals.

Conclusion

The present study provides evidence that the homologous SpV/SpV and heterologous SpV/Mod schemes showed good efficacy and safety under dialysis conditions. These results could be useful for future vaccination strategies, especially aimed at this risk group.
Modelling Road Accident Fatalities with Underdispersion and Zero-inflated Counts
Authors: Simmachan Teerawat , Wongsai Noppachai , Wongsai Sangdao , Lerdsuwansri Rattana
Published: May 2022

Background

Thailand was rank second in the world in 2013 on the road accident fatality (RAF) rate, killing 36.2 of every 100,000 Thai peoples. In the past decade, during Songkran festival, the traditional Thai new year, the number of road traffic accidents (RTAs) was markedly higher than normal day life, but few studies have yet investigated this issue as the effect of festivity. The objective of this study was to investigate factors contributing to RAF using various count regression models.

Methods

Data of 20,229 accidents in 2015 were collected from the Department of Disaster Prevention and Mitigation, Thailand. Poisson, Conway–Maxwell–Poisson, and their Zero-Inflated versions were applied to analyze factors associated with the number of fatalities in an accident.

Results

The RAFs in Thailand follow a count distribution with underdispersion and excessive zeros which is rare. The best fitting model, the ZICMP regression model returns significant predictors (road characteristics, weather conditions, environmental conditions, and month) on the number of fatalities in an accident. The model consists of the count part encapsulating both non-excess zeros and death counts and the zero-part representing the considerable number of zeros during the festival months. The estimated proportion of the zero-part is 0.275 accounting for 5,563 non-fatal accidents. More specifically, the excessive number of no deaths can be explained by the month factor. The mean number of fatalities was lower in the festive periods than other months, with the highest in November.

Conclusion

For long, Thai authorities have put a lot of efforts and resources into improving road safety over the festival weeks, often they failed. This study indicates that people’s risk perception and public awareness of RAFs are mislead. Instead, nationwide road safety should have been announced by the authorities to raise the awareness of society towards everyday personal safety and the safety of others.
Food Security after Nuclear Winter: A Preliminary Agricultural Sector Analysis for Aotearoa New Zealand
Authors: Wilson Nick , Prickett Marnie , Boyd Matt
Published: May 2022

Aim

We aimed to estimate the current dietary energy content of food exports for Aotearoa New Zealand (NZ) and food security after “nuclear winter” scenarios following a nuclear war.

Methods

From published sources we estimated dietary energy available from the major domains of food exports, with adjustments for wastage. The impacts on food production in NZ after three nuclear winter scenarios were based on those published inNature Foodin 2022 and from an earlier NZ Planning Council study.

Results

Current major food exports are equivalent to 3.9 times current dietary energy intakes for all NZ citizens ie, 34,100 kJ (8150 kcal) per person per day. Exported dairy products were estimated to be able to provide 338% of this energy intake, followed by exports of: meat (34%); fruit (8.6%), alcohol (4.8%), marine products (4.6%), and vegetables (2.7%). After the various nuclear winter scenarios considered (minimal to severe), food production available from diverted exported foods was estimated to still be 3.6 to 1.5 times current daily energy intakes.

Conclusions

This analysis suggests that NZ could have excess food production capacity, even after a severe nuclear winter scenario. But substantial further research is needed to clarify agricultural impacts and the role of nuclear war impacts on the interlinked domains of energy, transport, manufacturing, finance, industrial materials, trade and societal functioning.
Infectious viral shedding of SARS-CoV-2 Delta following vaccination: a longitudinal cohort study
Authors: Garcia-Knight Miguel , Anglin Khamal , Tassetto Michel , Lu Scott , Zhang Amethyst , Goldberg Sarah A. , Catching Adam , Davidson Michelle C. , Shak Joshua R. , Romero Mariela , Pineda-Ramirez Jesus , Sanchez Ruth Diaz , Rugart Paulina , Donohue Kevin , Massachi Jonathan , Sans Hannah M. , Djomaleu Manuella , Mathur Sujata , Servellita Venice , McIlwain David , Gaudiliere Brice , Chen Jessica , Martinez Enrique O. , Tavs Jacqueline M. , Bronstone Grace , Weiss Jacob , Watson John T. , Briggs-Hagen Melissa , Abedi Glen R. , Rutherford George W. , Deeks Steven G. , Chiu Charles , Saydah Sharon , Peluso Michael J. , Midgley Claire M. , Martin Jeffrey N. , Andino Raul , Kelly J. Daniel
Published: May 2022

The impact of vaccination on SARS-CoV-2 infectiousness is not well understood. We compared longitudinal viral shedding dynamics in unvaccinated and fully vaccinated adults. SARS-CoV-2-infected adults were enrolled within 5 days of symptom onset and nasal specimens were self-collected daily for two weeks and intermittently for an additional two weeks. SARS-CoV-2 RNA load and infectious virus were analyzed relative to symptom onset stratified by vaccination status. We tested 1080 nasal specimens from 52 unvaccinated adults enrolled in the pre-Delta period and 32 fully vaccinated adults with predominantly Delta infections. While we observed no differences by vaccination status in maximum RNA levels, maximum infectious titers and the median duration of viral RNA shedding, the rate of decay from the maximum RNA load was faster among vaccinated; maximum infectious titers and maximum RNA levels were highly correlated. Furthermore, amongst participants with infectious virus, median duration of infectious virus detection was reduced from 7.5 days (IQR: 6.0-9.0) in unvaccinated participants to 6 days (IQR: 5.0-8.0) in those vaccinated (P=0.02). Accordingly, the odds of shedding infectious virus from days 6 to 12 post-onset were lower among vaccinated participants than unvaccinated participants (OR 0.42 95% CI 0.19-0.89). These results indicate that vaccination had reduced the probability of shedding infectious virus after 5 days from symptom onset.

Significance statement

We present longitudinal data on the magnitude, duration and decay rate of viral RNA and the magnitude and duration of infectious virus in nasal specimens from vaccinated and unvaccinated participants. On average, vaccinated participants (infected with the highly transmissible Delta variant) showed a lower probability of having infectious virus after 5 days of symptoms compared to unvaccinated participants (infected with mostly pre-delta viral lineages), even though both groups had a similar magnitude of infectious virus at or near the peak. These data help improve our understanding of the duration of the infectious period when infection occurs following vaccination and serves as a reference for future studies of shedding dynamics following infections with novel variants of concern.
GRID1/GluD1 homozygous variants linked to intellectual disability and spastic paraplegia impair mGlu1/5 receptor signaling and excitatory synapses
Authors: Ung Dévina C. , Tricoire Ludovic , Pietrancosta Nicolas , Zlatanovic Andjela , Pode-Shakked Ben , Raas-Rothschild Annick , Elpeleg Orly , Abu-Libdeh Bassam , Hamed Nasrin , Papon Marie-Amélie , Marouillat Sylviane , Thépault Rose-Anne , Stevanin Giovanni , Lambolez Bertrand , Toutain Annick , Hepp Régine , Laumonnier Frédéric
Published: May 2022

The ionotropic glutamate delta receptor GluD1, encoded by theGRID1gene, is involved in synapse formation, function, and plasticity. GluD1 does not bind glutamate, but instead cerebellin and D-serine, which allow the formation of trans-synaptic bridges, and trigger transmembrane signaling. Despite wide expression in the nervous system, pathogenicGRID1variants have not been characterized in humans so far. We report homozygous missenseGRID1variants in five individuals from two unrelated consanguineous families presenting with intellectual disability and spastic paraplegia, without (p.Thr752Met) or with (p.Arg161His) diagnosis of glaucoma, a threefold phenotypic association whose genetic bases had not been elucidated previously. Molecular modeling indicated that Arg161His and Thr752Met mutations alter the hinge between GluD1 cerebellin and D-serine binding domains and the stiffness of this latter domain, respectively. Expression, trafficking, physical interaction with metabotropic glutamate receptor mGlu1, and cerebellin binding of GluD1 mutants were not conspicuously altered. Conversely, we found that both GluD1 mutants hampered signaling of metabotropic glutamate receptor mGlu1/5 via the ERK pathway in neurons of primary cortical culture. Moreover, both mutants impaired dendrite morphology and excitatory synapse density in neurons of primary hippocampal culture. These results show that the clinical phenotypes are distinct entities segregating in the families as an autosomal recessive trait, and caused by pathophysiological effects of GluD1 mutants involving metabotropic glutamate receptor signaling and neuronal connectivity. Our findings unravel the importance of the GluD1 receptor signaling in sensory, cognitive and motor functions of the human nervous system.
Somatic mutations reveal clonal cell populations in atherosclerotic plaques
Authors: Steffensen LB , Kavan S , Jensen PS , Møller-Larsen S , Larsen MK , Dembic M , Andersen LvB , Lindholt JS , Houlind KC , Thomassen M , Rasmussen LM
Published: May 2022

Background

In recent years, the potential involvement of clonal cell populations in atherosclerosis has gained renewed interest. Evidence from independent research groups unambiguously showed that smooth muscle cells clonally expand in experimental atherosclerosis, and clonal hematopoiesis of indeterminate potential (CHIP) has been proposed as a novel risk factor for atherosclerotic cardiovascular disease in humans. However, direct evidence for the presence of clonal cell populations within human atherosclerotic tissue is lacking.

Here, we investigated whether characterizing the mutational landscape of human atherosclerotic plaques could provide insights into the role of clonal cell populations in human atherosclerosis.

Methods and Results

We conductedin-depthwhole-exome sequencing of 65 samples derived from 13 carotid plaques obtained from patients undergoing carotid endarterectomy. This approach unveiled a landscape of somatic mutations exclusively confined to plaque tissue (i.e., not detected in patient-matched buffy coats). Leveraging variant allele frequencies, we inferred that distinct locally expanded clones often accounted for over 10% of the cell population within the plaque samples, and certain clones extended across multiple segments within the same plaque, necessitating a physical clone size of at least 1 cm. Furthermore, clones carrying multiple mutations spanned diverse plaque regions, encompassing the media, sub-core intima, and necrotic core. We did not detect any mutational hotspots, however, 21 of the mutated genes appeared in the Integrative Onco Genomics database of 619 mutational cancer driver genes (χ2test:p= 0.015). Moreover, unbiased pathway enrichment analysis disclosed enrichment of terms linked to cell-cell adhesion and the contractile apparatus, and genes underlying these enrichments were primarily expressed by smooth muscle cells, endothelial cells, and fibroblasts, as corroborated by analysis of single-cell RNA sequencing data. Finally, six patients were CHIP carriers, and in several of these patients, hematopoietic clones constributed significantly to the cell population of plaque segments.

Conclusions

In summary, our study provides compelling evidence that somatic mutations are an intrinsic aspect of human plaques. Moreover, we substantiate that specific mutation-carrying cells within plaque tissue undergo expansion, giving rise to clones of substantial size. We propose that unraveling the fundamental underpinnings of clonal biology and the phenotypic traits of expanding clones may unveil novel mechanisms to impede lesion development or enhance plaque stability.
Feasibility of a Novel Ultra-Low-Cost Bubble CPAP (bCPAP) System for Neonatal Respiratory Support at Muhimbili National Hospital, Tanzania
Authors: Tayler Ashtyn , Ashworth Henry , Saba Ghassan Bou , Wadhwa Hena , Dundek Michelle , Ng Ellie , Opondo Kennedy , Mkony Martha , Moshiro Robert , Burke Thomas
Published: May 2022

Objective

Continuous Positive Airway Pressure (CPAP) is recommended in the treatment of respiratory distress syndrome of premature newborns, however there are significant barriers to its implementation in low resource settings. The objective of this study was to evaluate the feasibility of use and integration of Vayu bCPAP Systems into the newborn unit at Muhimbili National Hospital in Tanzania.

Study Design

A Mixed Methods study was conducted from April 6 to October 6 2021. Demographic and clinical characteristics of patients treated with Vayu bCPAP Systems were collected and analyzed. Healthcare workers were interviewed until thematic saturation. Interviews were transcribed, coded, and analyzed using a framework analysis.

Results

370 patients were treated with Vayu bCPAP Systems during the study period. Mean birth weight was 1522 g (500-3800), mean duration of bCPAP treatment was 7.2 days (<1-39 d), and survival to wean was 81.4%. Twenty-four healthcare workers were interviewed and perceived Vayu bCPAP Systems as having become essential for treating neonatal respiratory distress at MNH. Key reasons were that Vayu bCPAP Systems improve patient outcomes, are easy to use, and more patients are now able to receive quality care. Barriers to integration included durability of oxygen tubing material and training.

Conclusions

It was feasible to implement and integrate Vayu bCPAP Systems into the care of neonates at Muhimbili National Hospital.
Tixagevimab/cilgavimab pre-exposure prophylaxis is associated with lower breakthrough infection risk in vaccinated solid organ transplant recipients during the Omicron wave
Authors: Jurdi Ayman Al , Morena Leela , Cote Mariesa , Bethea Emily , Azzi Jamil , Riella Leonardo V.
Published: May 2022

The neutralizing monoclonal antibody combination of tixagevimab/cilgavimab has been shown to reduce the risk of SARS-CoV-2 infection in unvaccinated individuals during the Alpha (B.1.1.7) and Delta (B.1.617.2) waves. However, data on efficacy and safety of tixagevimab/cilgavimab in vaccinated solid organ transplant recipients during the Omicron wave is limited. To address this, we conducted a retrospective cohort study comparing 222 solid organ transplant recipients who received tixagevimab/cilgavimab for pre-exposure prophylaxis and 222 age-matched vaccinated solid organ transplant recipients who did not receive tixagevimab/cilgavimab. Subjects were followed for a mean of 67 ± 18 days. Kaplan-Meier estimates of the 60-day incidence of breakthrough infection were 1.8% in the tixagevimab/cilgavimab group and 4.7% in the control group (P = 0.045). Adverse events were uncommon, occurring in 4% of our cohort and most were mild. There was no significant change in serum creatinine or liver chemistries in kidney and liver transplant recipients respectively. In conclusion, we found that tixagevimab/cilgavimab use is safe and associated with a lower risk of breakthrough SARS-CoV-2 infection in vaccinated solid organ transplant recipients during the Omicron wave.
Safety of the BNT162b2 mRNA COVID-19 Vaccine in Children below 5 Years (CoVacU5) – an Investigator-Initiated Retrospective Cohort Study
Authors: Töpfner Nicole , von Meißner Wolfgang C G , Strumann Christoph , Drinka Denisa , Stuppe David , Jorczyk Maximilian , Moor Jeanne , Püschel Johannes , Liss Melanie , Poblotzki Emilie von , Berner Reinhard , Moor Matthias B. , Chao Cho-Ming
Published: May 2022

Background

The safety of SARS-CoV-2 vaccines is unknown in children aged <5 years. Here, we retrospectively evaluated the safety of BNT162b2 vaccine used off-label in children of this age group in Germany.

Methods

An investigator-initiated retrospective cohort study (CoVacU5) included parents or caregivers having children aged <5 years registered for SARS-CoV-2 vaccination in outpatient care facilities in Germany. Reported short-term safety data of 1-3 doses of 3-10µg BNT162b2 in children aged 0 to <60 months are presented. Co-primary outcomes were the frequencies of 11 categories of symptoms post-vaccination with bivariate analyses and regression models adjusting for age, sex, weight and height. On-label non-SARS-CoV-2 vaccines served as controls in an active-comparator design.

Results

The study included 7806 of 19,000 registered children representing a 41% response rate. 338 children received the first dose of BNT162b2 at age 0-<12 months, n=1272 at age 12-24 months and n=5629 at age ≥24 to <60 months. A 10µg dosage was more frequently associated with injection-site symptoms compared to lower dosages. The probability of any symptoms (OR: 1.62 [95% confidence interval (CI): 1.36-1.94]), injection-site, musculoskeletal, dermatological or otolaryngological symptom categories were modestly elevated after BNT12b2 compared to non-SARS-CoV-2 vaccines, whereas the probabilities of general symptoms (OR: 0.74 [95% CI: 0.64-0.85]) and fever (OR: 0.43 [95% CI: 0.35-0.51]) were lower after BNT162b2. Symptoms requiring hospitalization (n=10) were reported only at BNT162b2 dosages higher than 3µg.

Conclusions

The symptoms reported after BNT162b2 administration were overall comparable to on-label non-SARS-CoV-2 vaccines in this cohort of children aged <5 years. (German Clinical Trials Register ID: DRKS00028759).
APOE modulates microglial immunometabolism in response to age, amyloid pathology, and inflammatory challenge
Authors: Lee Sangderk , Devanney Nicholas A. , Golden Lesley R. , Smith Cathryn T. , Schwarz James L. , Walsh Adeline E. , Clarke Harrison A. , Goulding Danielle S. , Allenger Elizabeth J. , Morillo-Segovia Gabriella , Friday Cassi M. , Gorman Amy A. , Hawkinson Tara R. , MacLean Steven M. , Williams Holden C. , Sun Ramon C. , Morganti Josh M. , Johnson Lance A.
Published: May 2022

The E4 allele of Apolipoprotein E (APOE) is associated with both metabolic dysfunction and a heightened pro-inflammatory response – two findings that may be intrinsically linked through the concept of immunometabolism. Here, we combined bulk, single-cell, and spatial transcriptomics with cell-specific and spatially resolved metabolic analyses to systematically address the role of APOE across age, neuroinflammation, and AD pathology. RNAseq highlighted immunometabolic changes across the APOE4 glial transcriptome, specifically in subsets of metabolically distinct microglia enriched in the E4 brain during aging or following an inflammatory challenge. E4 microglia display increased Hif1α expression, a disrupted TCA cycle, and are inherently pro-glycolytic, while spatial transcriptomics and MALDI mass spectrometry imaging highlight an E4-specific response to amyloid that is characterized by widespread alterations in lipid metabolism. Taken together, our findings emphasize a central role for APOE in regulating microglial immunometabolism.
SARM1 promotes axonal, synaptic, and mitochondrial pathologies in Charcot-Marie-Tooth disease type 2A
Authors: Sato-Yamada Yurie , Strickland Amy , Sasaki Yo , Bloom Joseph , DiAntonio Aaron , Milbrandt Jeffrey
Published: May 2022

Charcot-Marie-Tooth disease (CMT) type 2A is an axonal neuropathy caused by mutations in the mitofusin 2 (MFN2) gene. MFN2 mutations result in profound mitochondrial abnormalities, but the mechanism underlying axonal pathology is unknown. SARM1, the central executioner of axon degeneration, can induce neuropathy and is activated by dysfunctional mitochondria. We tested the role of SARM1 in a rat model carrying a dominant CMT2A mutation (Mfn2H361Y) that exhibits progressive dying-back axonal degeneration, NMJ abnormalities, muscle atrophy, and mitochondrial abnormalities, all hallmarks of the human disease. We generated Sarm1 knockout and Mfn2H361Y, Sarm1 double mutant rats and find that deletion of SARM1 rescues axonal, synaptic, and muscle phenotypes, demonstrating that SARM1 induces much of the neuropathology in this model. Despite the presence of mutant Mfn2 protein in these double mutant rats, loss of SARM1 also dramatically suppressed many mitochondrial defects, including the number, size, and cristae density defects of synaptic mitochondria. This surprising finding indicates that dysfunctional mitochondria activate SARM1, and activated SARM1 feeds back on mitochondria to exacerbate mitochondrial pathology. As such, this work identifies SARM1 inhibition as an exciting therapeutic candidate for the treatment of CMT2A and other neurodegenerative diseases with prominent mitochondrial pathology.
Feasibility and Utility of a Structured Guide for Cannabis Tolerance Breaks in Young Adults
Authors: Fontana Thomas JK , Schulz Jonathan A. , Budney Alan J. , Villanti Andrea C.
Published: May 2022

Objective

To explore the feasibility and utility of a tolerance break (T-Break) guide on young adults’ cannabis use.

Participants

Young adults aged 18-29 (n=125) who were current cannabis users.

Methods

Participants recruited through posters and listservs at various universities were offered the T-Break Guide—daily activities, advice, and encouragement—to help complete a 21-day cannabis break. Bivariate analyses examined associations between Guide use and follow-up measures.

Results

Compared to non-Guide users, participants who used the Guide “a lot” were more likely to complete the 21-day abstinence break (84% vs. 57%), revise their personal definition of balance to mean less cannabis (84% vs. 62%), and plan a future break (32% vs. 11%).

Conclusion

Use of this self-directed Guide may help young adults take a break from cannabis use and reduce future use. Further research using more rigorous designs to test the Guide’s efficacy and assess longer-term maintenance of effects is needed.
Gene expression based molecular test proves clinical validity as diagnostic aid for the differential diagnosis of psoriasis and eczema in formalin fixed and paraffin embedded tissue
Authors: Fischer Felix , Roenneberg Sophie , Graner Larissa , Schlenker Franziska , Zengerle Roland , Theis Fabian J. , Schmidt-Weber Carsten B. , Biedermann Tilo , Lauffer Felix , Garzorz-Stark Natalie , Eyerich Stefanie
Published: May 2022

Highly specific and efficient drugs have been developed during the last two decades to treat non-communicable chronic inflammatory skin diseases (ncISD). Due to their specificity, these drugs are asking for precise diagnostic measures to attribute the most efficient treatment to each patient. Diagnosis, however, is complicated by the complex pathogenesis of ncISD and their clinical and histological overlap. Especially, precise diagnosis of psoriasis and eczema is difficult in special cases and molecular diagnostic tools need to be developed to support gold standard diagnosis of patients. In this line, we have developed a real-time based molecular classifier to distinguish psoriasis from eczema in RNA-later fixed skin samples. However, this type of skin sample is not regularly used in routine diagnostics. Therefore, we evaluated if the combination of NOS2 and CCL27 expression in lesional skin can be transferred to formalin-fixed paraffin embedded (FFPE) tissue. We present a FFPE-based molecular classifier (MC) that determines the probability for psoriasis with a specificity and sensitivity of 100% and 92%, respectively, and an area under the curve (AUC) of 0.97 delivering comparable results to the RNA-later based MC. The probability for psoriasis as well as the PCR result of NOS2 expression correlated positive with disease hallmarks of psoriasis and negative with eczema hallmarks. This tool now offers broad usage in pathology laboratories and can support diagnostic decision making on a molecular level.
Risk of Plasmodium vivax recurrences follows a 30-70 rule and indicates relapse heterogeneity in the population
Authors: Stadler Eva , Cromer Deborah , Mehra Somya , Adekunle Adeshina I , Flegg Jennifer A , Anstey Nicholas M , Watson James A , Chu Cindy S , Mueller Ivo , Robinson Leanne J , Schlub Timothy E , Davenport Miles P , Khoury David S
Published: May 2022

A key characteristic of Plasmodium vivax parasites is their ability to adopt a latent liver-stage form called hypnozoites, able to cause relapse of infection months or years after a primary infection. Relapses of infection through hypnozoite activation are a major contributor to blood-stage infections in P vivax endemic regions and are thought to be influenced by factors such as febrile infections, immunity, and transmission intensity. Some of these factors may cause temporary changes in hypnozoite activation over time, leading to ‘temporal heterogeneity’ in reactivation risk. In addition, variation in exposure to infection may be a longer-term characteristic of individuals that leads to ‘population heterogeneity’ in hypnozoite activation. We analyze data on risk of P vivax in two previously published data sets from Papua New Guinea and the Thailand-Myanmar border region. Modeling different mechanisms of reactivation risk, we find strong evidence for population heterogeneity, with 30% of patients having almost 70% of all P vivax infections. Model fitting and data analysis indicates that individual variation in relapse risk is a primary source of heterogeneity of P vivax risk of recurrences.
Opposing and emotion-specific frontal alterations during facial emotion processing in generalized anxiety and depression
Authors: Chen Yuanshu , Liu Congcong , Xin Fei , Haocen Zhou , Huang Yulan , Wang Jinyu , Dai Jing , Zou Zhili , Ferraro Stefania , Kendrick Keith M , Zhou Bo , Xu Xiaolei , Becker Benjamin
Published: May 2022

Background

Major depression (MDD) and generalized anxiety disorder (GAD) have become one of the leading global causes of disability and both are characterized by marked interpersonal and social impairments. However, despite a high comorbidity and overlapping social-emotional deficits it remains unclear whether MDD and GAD share a common neural basis during interpersonal processing.

Methods

This study combined an emotional face processing paradigm with fMRI and dimensional and categorical analyses in a sample of unmedicated MDD and GAD patients (N = 72) as well as healthy controls (N = 35).

Results

No group differences were found in categorical analyses. However, the dimensional analyses revealed that dorsolateral prefrontal cortex (dlPFC) reactivity to sad facial expressions was positively associated with depressive, yet negatively associated with GAD symptom load in the entire sample. On the network level depression symptom load was positively associated with functional connectivity between the bilateral amygdala and a widespread network including the anterior cingulate and insular cortex.

Limitations

Sex differences were not examined in the present study and some patients exhibited depression-GAD comorbidity.

Conclusions

Together, these findings suggest that the dlPFC - engaged in cognitive and emotional processing - exhibits symptom- and emotion-specific alteration during interpersonal processing. Dysregulated communication between amygdala and core regions of the salience network may represent MDD-specific neural dysregulations.
Early experience with modified dose nirmatrelvir/ritonavir in dialysis patients with coronavirus disease-2019
Authors: Brown Pierre Antoine , McGuinty Michaeline , Argyropoulos Christos , Clark Edward G , Colantonio David , Giguere Pierre , Hiremath Swapnil
Published: May 2022

Introduction

Nirmatrelvir/Ritonavir was approved for use in high risk outpatients with coronavirus disease (COVID-19). However, patients with severe chronic kidney disease, including patients on dialysis, were excluded from the phase 3 trial, and currently the drug is not recommended below a glomerular filtration rate of 30 ml/min/1.73m2. Based on available pharmacological data and principles, we developed a modified dose which was lower, and administered at longer intervals.We administered nirmatrelvir/ritonavir as 300/100 mg on day one, followed by 150/100 mg daily from day two to day five. In this case series, we report the initial experience with this modified dose regimen.

Methods

This is a retrospective chart review, conducted after obtaining institutional board approval. Demographic and outcome data was abstracted from the electronic medical record for dialysis patients who developed COVID-19 during the period of study and received nirmatrelvir/ritonavir. The principal outcomes we describe are symptom resolution, and safety data with the modified dose regimen in the dialysis patients.

Results

19 patients developed COVID-19 during the period of study of whom 15 received nirmatrelvir/ritonavir. 47% of them were female and 67% had diabetes. Most patients had received three doses of the vaccine (80%) while 13% were unvaccinated. Potential drug interactions concerns were common (median 2 drugs per patient) with amlodipine and atorvastatin being the commonest drugs requiring dose modification. Nirmatrelvir/ritonavir use was associated with symptom resolution in all patients, and was well tolerated. One patient had a rebound of symptoms, which improved in 2 more days. There were no COVID-19 related hospitalizations or deaths in any of the patients.

Conclusion

In this case series of 15 hemodialysis patients with COVID-19, a modified dose of nirmatrelvir/ritonavir use, with pharmacist support for drug interaction management, was associated with symptom resolution, and was well tolerated with no serious adverse effects.
Changes in immunoglobulin levels during clozapine treatment in schizophrenia
Authors: Griffiths Kira , Mellado Maria Ruiz , Chung Raymond , Lally John , McQueen Grant , Sendt Kyra-Verena , Gillespie Amy , Ibrahim Muhammad , Richter Alex , Shields Adrian , Ponsford Mark , Jolles Stephen , Hodsoll John , Pollak Thomas , Upthegrove Rachel , Egerton Alice , MacCabe James H
Published: May 2022

Background

Clozapine is the only licensed pharmacotherapy for patients with treatment-resistant schizophrenia (TRS), but its use is limited due to adverse effects. Clozapine treatment has been recently associated with reductions in immunoglobulin (Ig) levels cross-sectionally, however prospective studies are required to establish longitudinal effects. This study aimed to determine whether reductions in immunoglobulin levels occur over 6 months after initiating clozapine treatment. An exploratory aim was to investigate relationships between immunoglobulin levels and symptom severity over the course of clozapine treatment.

Methods

In 56 participants with TRS, Ig A, M and G levels were measured in serum using a sandwich immunoassay. Samples for analysis were acquired prior to starting clozapine and at 6, 12 and 24 weeks after initiating clozapine treatment. Clinical symptoms were measured using the positive and negative syndrome scale for schizophrenia (PANSS).

Results

All three classes of Ig decreased during clozapine treatment. For IgA and IgG the reduction was significant at 24 weeks (IgA: B – 32.7, 95% CI = -61.19, -4.2, p = 0.04; IgG: B – 55.94, 95% CI = -111.03, -0.844, p = 0.05). For IgM the reduction was significant at 12 and 24 weeks (12 weeks: B = -21.73, 95% CI = -37.10, -6.35, p = 0.006; 24 weeks: B = -32.54, 95% CI = -48.89, 16.18, p = 0.0001). Changes in both IgA and IgG were correlated with the percentage change in PANSS total scores over 12 weeks, such that greater reductions in IgA and IgG during clozapine treatment were associated with greater reductions in symptom severity (n = 32, IgA r = 0.59, p = 0.005; IgG r = 0.50, p = 0.02)

Conclusions

The observed reductions in immunoglobulin levels over six months of clozapine treatment add further evidence linking clozapine to secondary antibody deficiency. The associations between Ig reduction and symptom improvement may however indicate that immune mechanisms contribute to both desirable and undesirable effects of clozapine.