bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Phenotypes and Outcomes in Monogenic Versus Non-monogenic Very Early Onset Inflammatory Bowel Disease
Authors: Collen Lauren V , Kim David Y , Field Michael , Okoroafor Ibeawuchi , Saccocia Gwen , Whitcomb Sydney Driscoll , Green Julia , Dong Michelle Dao , Barends Jared , Carey Bridget , Weatherly Madison E ,   Regeneron Genetics centre, Rockowitz Shira , Sliz Piotr , Liu Enju , Eran Alal , Grushkin-Lerner Leslie , Bousvaros Athos , Muise Aleixo M , Klein Christoph , Mitsialis Vanessa , Ouahed Jodie , Snapper Scott B
Published: April 2022

Background and Aims

Over 80 monogenic causes of very early onset inflammatory bowel disease [VEOIBD] have been identified. Prior reports of the natural history of VEOIBD have not considered monogenic disease status. The objective of this study is to describe clinical phenotypes and outcomes in a large single-centre cohort of patients with VEOIBD and universal access to whole exome sequencing [WES].

Methods

Patients receiving IBD care at a single centre were prospectively enrolled in a longitudinal data repository starting in 2012. WES was offered with enrollment. Enrolled patients were filtered by age of diagnosis <6 years to comprise a VEOIBD cohort. Monogenic disease was identified by filtering proband variants for rare, loss-of-function, or missense variants in known VEOIBD genes inherited according to standard Mendelian inheritance patterns.

Results

This analysis included 216 VEOIBD patients, followed for a median of 5.8 years. Seventeen patients [7.9%] had monogenic disease. Patients with monogenic IBD were younger at diagnosis and were more likely to have Crohn’s disease phenotype with higher rates of stricturing and penetrating disease and extraintestinal manifestations. Patients with monogenic disease were also more likely to experience outcomes of intensive care unit [ICU] hospitalisation, gastrostomy tube, total parenteral nutrition use, stunting at 3-year follow-up, haematopoietic stem cell transplant, and death. A total of 41 patients [19.0%] had infantile-onset disease. After controlling for monogenic disease, patients with infantile-onset IBD did not have increased risk for most severity outcomes.

Conclusions

Monogenic disease is an important driver of disease severity in VEOIBD. WES is a valuable tool in prognostication and management of VEOIBD.
GuideMaker: Software to design CRISPR-Cas guide RNA pools in non-model genomes
Authors: Poudel Ravin , Rodriguez Lidimarie Trujillo , Reisch Christopher R , Rivers Adam R
Published: April 2022

Background

CRISPR-Cas systems have expanded the possibilities for gene editing in bacteria and eukaryotes. There are many excellent tools for designing CRISPR-Cas guide RNAs (gRNAs) for model organisms with standard Cas enzymes. GuideMaker is intended as a fast and easy-to-use design tool for challenging projects with (i) non-standard Cas enzymes, (ii) non-model organisms, or (iii) projects that need to design a panel of gRNA for genome-wide screens.

Findings

GuideMaker can rapidly design gRNAs for gene targets across the genome using a degenerate protospacer-adjacent motif (PAM) and a genome. The tool applies hierarchical navigable small world graphs to speed up the comparison of guide RNAs and optionally provides on-target and off-target scoring. This allows the user to design effective gRNAs targeting all genes in a typical bacterial genome in ∼1–2 minutes.

Conclusions

GuideMaker enables the rapid design of genome-wide gRNA for any CRISPR-Cas enzyme in non-model organisms. While GuideMaker is designed with prokaryotic genomes in mind, it can efficiently process eukaryotic genomes as well. GuideMaker is available as command-line software, a stand-alone web application, and a tool in the CyCverse Discovery Environment. All versions are available under a Creative Commons CC0 1.0 Universal Public Domain Dedication.
Prevalence, Pathogenesis and Management of Anemia in Inflammatory Bowel Disease: An IG-IBD Multicenter, Prospective, and Observational Study
Authors: Bergamaschi Gaetano , Castiglione Fabiana , D’Incà Renata , Astegiano Marco , Fries Walter , Milla Monica , Ciacci Carolina , Rizzello Fernando , Saibeni Simone , Ciccocioppo Rachele , Orlando Ambrogio , Bossa Fabrizio , Principi Mariabeatrice , Vernia Piero , Ricci Chiara , Scribano Maria L , Bodini Giorgia , Mazzucco Dario , Bassotti Gabrio , Riegler Gabriele , Buda Andrea , Neri Matteo , Caprioli Flavio , Monica Fabio , Manca Aldo , Villa Erica , Fiorino Gionata , Comberlato Michele , Aronico Nicola , Della Corte Cristina , Caccaro Roberta , Gionchetti Paolo , Giuffrida Paolo , Iovino Paola , Lenti Marco V , Mengoli Caterina , Pellegrini Lucienne , Pieraccini Alberto , Ribaldone Davide , Testa Anna , Ubezio Cristina , Viola Anna , Vecchi Maurizio , Klersy Catherine , Di Sabatino Antonio
Published: April 2022

Background

Anemia is a common extraintestinal manifestation of inflammatory bowel disease (IBD), with a 6% to 74% prevalence and a negative impact on patient survival and quality of life, although the prevalence is apparently declining due to improved disease treatment. We aimed to investigate the prevalence, pathogenesis, and clinical correlates of anemia in Italian patients with IBD.

Methods

A multicenter, prospective, observational study, involving 28 Italian gastroenterology centers, was conducted to investigate the epidemiology and consequences of IBD-associated anemia. Clinical and laboratory data of anemic patients were obtained at study enrolment.

Results

Anemia was diagnosed in 737 of 5416 adult IBD outpatients (prevalence 13.6%); females were more commonly affected than males (odds ratio, 1.5; 95% confidence interval [CI], 1.2–1.7) and had more severe anemia. In the majority of cases, anemia was due to iron deficiency (62.5% of cases; 95% CI, 58.3%–66.6%), either isolated or in association with inflammation and/or vitamin deficiencies; anemia of inflammation accounted for only 8.3% of cases. More severe anemia was associated with increasing fatigue and worse quality of life. Only 68.9% of anemic patients with iron deficiency (95% CI, 63.4%–73.8%) and 34.6% of those with vitamin deficiencies (95% CI, 26.2%–44.2%) were properly treated with supplementation therapy.

Conclusions

In Italy, the prevalence of IBD-associated anemia is lower than previously reported. Anemia of IBD is most commonly due to iron deficiency and contributes to fatigue and poor quality of life, but remains untreated in a large proportion of patients with iron and/or vitamin deficiencies. This study is registered at clinicaltrials.gov as NCT02872376.
Characterizing Balsam Woolly Adelgid Infestations and Associated Tree Mortality in Idaho
Authors: Davis Gina A , Lowrey Laura , Eckberg Tom , Hicke Jeffrey A , Smirnova Ekaterina
Published: April 2022

Balsam woolly adelgid, Adelges piceae (BWA), is a nonnative insect that has invaded much of the true fir range in North America, reducing host tree growth and causing mortality. Here, we describe a field study to characterize BWA infestation and effects on host trees in Idaho from the onset of infestation within twenty-eight sites with repeated surveys in 2008, 2013, and 2018. Declining tree health was categorized into five BWA damage classes based on the percent of the tree crown–expressing symptoms caused by BWA. Between 2008 and 2018, BWA presence increased across most sites regardless of host species, with an average of 48% (0.1%–100%) host trees per acre being infested. Severe damage or mortality of true fir from BWA occurred across thirteen sampled forest habitat types, including those representing harsh, high elevations. Although a significantly greater proportion of subalpine fir died than grand fir by 2018, BWA caused grand fir mortality. All diameter size classes became infested with BWA, including seedlings, and BWA caused mortality regardless of tree diameter. This assessment provides baseline data for a deeper analysis of insect, host, stand, and environmental interactions that may elucidate factors driving severe stand mortality.

Study Implications

Balsam woolly adelgid (BWA) is a cryptic, nonnative, and chronically lethal insect of true firs that is frequently overlooked until tree health substantially declines. Therefore, it is often not considered a serious damage agent during forest management planning until after severe damage has occurred across a stand. The BWA damage classification, modified from Spiegel et al. (2013), may be applied during stand exams. This simple and effective five-tiered classification system can be used to categorize BWA damage within individual trees or stands based on the collective symptoms caused by the insect. Feeding by BWA can ultimately result in stand-level mortality of both over- and understory fir and may require artificial regeneration to restore forest function. Fir regeneration was abundant at most BWA-damaged sites; however, seedling-sized firs were often heavily gouted from BWA to levels that will prevent them from growing into seed-bearing trees. Reported levels of mortality caused by BWA within 10 years of infestation and forest habitat type associations can be referenced for making management decisions for not-yet or recently infested stands.
An accurate strategy for computing reaction forces and fluxes on trimmed locally refined meshes
Authors: D’Angella Davide , Kollmannsberger Stefan , Reali Alessandro , Rank Ernst , Hughes Thomas J R
Published: April 2022

The finite element method is classically based on nodal Lagrange basis functions defined on conforming meshes. In this context, total reaction forces are commonly computed from the so-called “nodal forces”, yielding higher accuracy and convergence rates than reactions obtained from the differentiated primal solution (“direct” method). The finite cell method and isogeometric analysis promise to improve the interoperability of computer-aided design and computer-aided engineering, enabling a direct approach to the numerical simulation of trimmed geometries. However, body-unfitted meshes preclude the use of classic nodal reaction algorithms. This work shows that the direct method can perform particularly poorly for immersed methods. Instead, conservative reactions can be obtained from equilibrium expressions given by the weak problem formulation, yielding superior accuracy and convergence rates typical of nodal reactions. This approach is also extended to non-interpolatory basis functions, such as the (truncated) hierarchical B-splines.
On the Provision of Health Services and Protection of Health Workers in War: A Review of Leonard Rubenstein’s Perilous Medicine
Authors: Boetig Bradley
Published: April 2022

This review critiques Johns Hopkins professor Leonard Rubenstein’s Perilous Medicine: The Struggle to Protect Health Care from the Violence of War, and offers the reader a military medical officer’s perspective on these important concepts. Rubenstein’s tome is essential reading for military officers who must understand how the laws of armed conflict and the ideals of humanitarian protection apply in twenty-first-century conflict. This review adds that military officers may, at times, need to also consider a less ideal but more consequential framework.
Hispanic/Latinx Ethnic Subgroup Differences in Sociodemographic, Sociocultural, and Smoking Characteristics in a Cessation Trial: An Exploratory Study
Authors: Medina-Ramirez Patricia , Casas Laura , Sutton Steven K , Calixte-Civil Patricia , Brandon Karen O , Martinez Ursula , Meade Cathy D , Byrne Margaret M , Brandon Thomas H , Simmons Vani N
Published: April 2022

Introduction

Hispanic/Latinx smokers in the United States are often treated as a homogeneous group. However, population-based studies suggest that cigarette use differs among Hispanic/Latinx subgroups by sociodemographic or sociocultural characteristics. This secondary analysis aimed to advance the limited literature by examining differences in smoking-related variables.

Aims and Methods

We used baseline data from a randomized controlled trial testing a self-help Spanish-language smoking cessation intervention. Puerto Rican (PR), Mexican, and Cuban, the three largest Hispanic/Latinx subgroups in the sample (N = 1028), were first compared on sociodemographic and sociocultural variables (acculturation and familism). Primary analyses assessed subgroup differences in cigarette use variables (eg, cigarettes per day [CPD], nicotine dependence [Fagerström Test for Nicotine Dependence], and daily smoking) and smoking-related cognitive constructs (motivation to quit, smoking outcome expectancies, and abstinence self-efficacy) controlling for sociodemographic and sociocultural variables. Additional analyses explored differences between men and women within subgroups.

Results

Mexicans exhibited the lowest levels of daily smoking (90% vs. 95% Cubans and 96% PR; p = .001), CPD (M = 13.5, SD = 9.5 vs. M = 20.1, SD = 9.9 Cubans and M = 16.7, SD = 10.1 PR; p = .016), and nicotine dependence (M = 4.2, SD = 2.3 vs. M = 6.0, SD = 2.1 Cubans and M = 5.7, SD = 2.2 PR; p < .001), with no differences between PRs and Cubans. Within-subgroup comparisons between men and women showed the most differences among PRs (eg, men were more nicotine dependent [M = 6.0, SD = 1.9] than women [M = 5.4, SD = 2.3; p = .041]) and Cubans (eg, men smoked more CPD [M = 22.2, SD = 12.2] than women [M = 19.3, SD = 12.0; p = .042]), and the fewest among Mexicans.

Conclusions

Findings support heterogeneity within Hispanic/Latinx smokers and highlight the potential utility of examining sociodemographic, sociocultural, and smoking characteristics important for developing salient cessation interventions.

Implications

Findings demonstrate that treatment-seeking Hispanic/Latinx smokers in the United States differ in sociodemographic, sociocultural, and smoking-related variables (cigarette use and smoking-related cognitive constructs) by subgroup (ie, PR, Mexican, and Cuban) and within subgroups by sex. These differences suggest that heterogeneity among subgroups should be considered when developing cessation interventions for Hispanics/Latinxs. Future research should examine how differences in sociodemographic and smoking-related variables impact intervention outcomes and explore the role of sociocultural factors (eg, acculturation and familism) as determinants of cessation.
Evaluation of Fungicide Soil Drench Treatments to Manage Black Root Rot Disease of Avocado
Authors: Prabhakaran Akila D. , Dann Elizabeth K.
Published: April 2022

Four common fungicidal products were evaluated for their effect on symptoms caused by two nectriaceous black root rot fungi, Calonectria ilicicola and Dactylonectria macrodidyma, when applied as pot drenches to avocado (Persea americana) seedlings in the greenhouse. Applications of fludioxonil, thiophanate-methyl + etridiazole, prochloraz, and prochloraz MnCl at 2 and 4 weeks after inoculation with C. ilicicola significantly reduced root necrosis and improved root and aboveground plant biomass compared with water-treated controls. Fludioxonil reduced necrosis by 60% and had a significantly lower frequency of reisolation of C. ilicicola than the other three fungicide treatments. D. macrodidyma inoculation caused less severe symptoms in seedlings than C. ilicicola despite the longer duration of the trial. Pot drenches with fludioxonil, thiophanate-methyl + etridiazole, and prochloraz MnCl, but not prochloraz alone, significantly reduced root necrosis caused by D. macrodidyma. Prochloraz MnCl was the only fungicide treatment to increase root and plant biomass compared with water-treated controls. Both fludioxonil and prochloraz MnCl reduced the frequency of reisolation of D. macrodidyma from necrotic roots by about 50% compared with the other fungicides or water controls. The results indicated that drenches with these fungicides may suppress existing low to moderate black root rot infection, allowing new root growth and improved establishment in the orchard. Fungicide drenching must not replace best-practice disease management strategies in nurseries but may be a useful tool in crisis situations.
Proteome-Wide Response of Dormant Caryopses of the Weed, Avena fatua, After Colonization by a Seed-Decay Isolate of Fusarium avenaceum
Authors: Lewis Ricky W. , Okubara Patricia A. , Sullivan Tarah S. , Madden Benjamin J. , Johnson Kenneth L. , Charlesworth M. Cristine , Fuerst E. Patrick
Published: April 2022

Promoting seed decay is an ecological approach to reducing weed persistence in the soil seedbank. Previous work demonstrated that Fusarium avenaceum F.a.1 decays dormant Avena fatua (wild oat) caryopses and induces several defense enzyme activities in vitro. The objectives of this study were to obtain a global perspective of proteins expressed after F.a.1-caryopsis colonization by conducting proteomic evaluations on (i) leachates, soluble extrinsic (seed-surface) proteins released upon washing caryopses in buffer and (ii) proteins extracted from whole caryopses; interactions with aluminum (Al) were also evaluated in the latter study because soil acidification and associated metal toxicity are growing problems. Of the 119 leachate proteins classified as defense/stress, 80 were induced or repressed. Defense/stress proteins were far more abundant in A. fatua (35%) than in F.a.1 (12%). Avena defense/stress proteins were also the most highly regulated category, with 30% induced and 35% repressed by F.a.1. Antifungal proteins represented 36% of Avena defense proteins and were the most highly regulated, with 36% induced and 37% repressed by F.a.1. These results implicate selective regulation of Avena defense proteins by F.a.1. Fusarium proteins were also highly abundant in the leachates, with 10% related to pathogenicity, 45% of which were associated with host cell wall degradation. In whole caryopsis extracts, fungal colonization generally resulted in induction of a similar set of Avena proteins in the presence and absence of Al. Results advance the hypothesis that seed decay pathogens elicit intricate and dynamic biochemical responses in dormant seeds.
Acceptability and associated factors of indoor residual spraying for Malaria control by households in Luangwa district of Zambia: A multilevel analysis
Authors: Aongola Maureen , Kaonga Patrick , Michelo Charles , Zgambo Jessy , Lupenga Joseph , Jacobs Choolwe
Published: April 2022

Background

The global burden of malaria has increased from 227 million cases in 2019 to 247 million cases in 2020. Indoor residual spraying (IRS) remains one of the most effective control strategies for malaria. The current study sought to measure the acceptability level and associated factors of indoor residual spraying.

Methods

A cross sectional study was conducted from October to November 2020 in sixteen urban and rural communities of Luangwa district using a cluster sampling method, Multilevel analysis was used to account for the hierarchical structure of the data.

Results

The acceptability level of indoor residual spraying among household heads was relatively high at 87%. Individuals who felt the timing was not appropriate were associated with decreased odds of accepting IRS (AOR = 0.55, 95% CI: 0.20 - 0.86). Positive attitude was associated with increased odds of accepting IRS (AOR = 29.34, 95% CI: 11.14 - 77.30). High acceptability level was associated with unemployment (AOR = 1.92, 95% CI: 1.07 - 3.44). There were no associations found between acceptability levels and community-level factors such as information, education, communication dissemination, awareness achieved through door-to-door sensitization, and public address system.

Conclusion

Acceptability level of indoor residual spraying was relatively high among households of Luangwa District suggesting that the interventions are more acceptable which is essential in reaching malaria elimination by 2030. Finding that community factors known to influence acceptability such as information, education and communication as well as awareness were not important to influencing acceptability suggests need for reinforcing messages related to indoor residual spraying and redefining the community sensitization approaches to make indoor residual spraying more acceptable.
Declining Course of Humoral Immune Response in Initially Responding Kidney Transplant Recipients after Repeated SARS-CoV-2 Vaccination
Authors: Ronicke Simon , Osmanodja Bilgin , Budde Klemens , Jens Annika , Hammett Charlotte , Koch Nadine , Zukunft Bianca , Bachmann Friederike , Choi Mira , Weber Ulrike , Eberspächer Bettina , Hofmann Jörg , Grunow Fritz , Mikhailov Michael , Halleck Fabian , Schrezenmeier Eva
Published: April 2022

Immunogenicity of SARS-CoV-2 vaccines in kidney transplant recipients is limited, resulting in inadequately low serological response rates and low immunoglobulin (Ig) levels, correlating with reduced protection against death and hospitalization from COVID-19. We retrospectively examined the time course of anti-SARS-CoV-2 Ig antibody levels after up to five repeated vaccinations in 644 previously nonresponding kidney transplant recipients. Using anti SARS-CoV-2 IgG/IgA ELISA and the total Ig ECLIA assays, we compare antibody levels at 1 month with levels at 2 and 4 months, respectively. Additionally, we correlate the measurements of the used assays.

Between 1 and 2 months, and between 1 and 4 months, mean anti-SARS-CoV-2 Ig levels in responders decreased by 14% and 25%, respectively, depending on the assay. Absolute Ig values and time course of antibody levels and showed high interindividual variability. Ig levels decreased by at least 20% in 77 of 148 paired samples with loss of sufficient serological protection over time occurring in 18 out of 148 (12.2%).

IgG ELISA and total Ig ECLIA assays showed a strong positive correlation (Kendall’s tau=0.78), yet the two assays determined divergent results in 99 of 751 (13.2%) measurements. IgG and IgA assays showed overall strong correlation but divergent results in 270 of 1.173 (23.0%) cases and only weak correlation of antibody levels in positive samples.

Large interindividual variability and significant loss of serological protection after 4 months supports repeated serological sampling and consideration of shorter vaccination intervals in kidney transplant recipients.
Impact of Total Hip Replacements on the Incidence of Hip Fractures in Norway During 1999–2019. A NOREPOS Study
Authors: Kjeldgaard Helena Kames , Meyer Haakon E , O’Flaherty Martin , Apalset Ellen M , Dahl Cecilie , Emaus Nina , Fenstad Anne Marie , Furnes Ove , Gjertsen Jan-Erik , Hoff Mari , Schei Berit , Søgaard Anne Johanne , Tell Grethe S , Holvik Kristin
Published: April 2022

The knowledge about why hip fracture rates in Norway have declined is sparse. Concurrent with decreasing hip fracture rates, the rates of total hip replacements (THRs) have increased. We wanted to investigate if hip fracture rates continued to decline, and whether the increase in THRs had any influence on this decline, assuming that living with a hip prosthesis precludes fracture of the operated hip. Information on hip fractures in Norway 1999-2019 was available from the Norwegian Epidemiologic Osteoporosis Studies (NOREPOS) hip fracture database and population size were available in official population tables from Statistics Norway. Primary THRs (for any cause except hip fracture) 1989-2019 were obtained from the Norwegian Arthroplasty Register. We calculated the annual age-standardized incidence rates of hip fracture by sex for the period 1999–2019. The hip fracture rates in a scenario with no hip prostheses were calculated by subtracting 0.5 persons from the population at risk for each prevalent hip prosthesis, considering that each person has two hips at risk of fracture. We estimated how much of the decline could be attributed to the increased prevalence of hip prostheses. From 1999 to 2019, age-standardized incidence rates of hip fracture decreased by 27% in women and 20% in men. The rates remained stable in those under 70 years and decreased in those 70 years and above. Excluding replaced hips from the population at risk led to higher incidence rates, and this impact was considerably larger at higher ages. The increased prevalence of hip prostheses over the period accounted for approximately 18% (20% in women and 11% in men) of the observed decline in hip fracture rates. In conclusion, the incidence of hip fractures continued to decline, and the increasing number of people living with hip prostheses contributed significantly to the observed declining time trends.
VentRa. Validation study of the ventricle feature estimation and classification tool to differentiate behavioral variant frontotemporal dementia from psychiatric disorders and other degenerative diseases
Authors: Manera Ana L. , Dadar Mahsa , Ducharme Simon , Collins D. Louis
Published: April 2022

Introduction

Lateral ventricles are reliable and sensitive indicators of brain atrophy and disease progression in behavioral variant frontotemporal dementia (bvFTD). Here we validate our previously developed automated tool using ventricular features (known as VentRa) for the classification of bvFTD vs a mixed cohort of neurodegenerative, vascular, and psychiatric disorders from a clinically representative independent dataset.

Methods

Lateral ventricles were segmented for 1110 subjects - 14 bvFTD, 30 other Frontotemporal Dementia (FTD), 70 Lewy Body Disease (LBD), 898 Alzheimer Disease (AD), 62 Vascular Brain Injury (VBI) and 36 Primary Psychiatric Disorder (PPD) from the publicly accessible National Alzheimer’s Coordinating Center dataset to assess the performance of VentRa.

Results

Using ventricular features to discriminate bvFTD subjects from PPD, VentRa achieved an accuracy of 84%, 71% sensitivity and 89% specificity. VentRa was able to identify bvFTD from a mixed age-matched cohort (i.e., Other FTD, LBD, AD, VBI and PPD) and to correctly classify other disorders as ‘not compatible with bvFTD’ with a specificity of 83%. The specificity against each of the other individual cohorts were 80% for other FTD, 83% for LBD, 83% for AD and 84% for VBI.

Discussion

VentRa is a robust and generalizable tool with potential usefulness for improving the diagnostic certainty of bvFTD, particularly for the differential diagnosis with PPD.
Effect ofMAOADNA methylation on humanin vivoprotein expression measured by [11C]harmine PET in healthy and depressed individuals
Authors: Handschuh Patricia A. , Murgaš Matej , Vraka Chrysoula , Nics Lukas , Hartmann Annette M. , Winkler-Pjrek Edda , Baldinger-Melich Pia , Wadsak Wolfgang , Winkler Dietmar , Hacker Marcus , Rujescu Dan , Domschke Katharina , Lanzenberger Rupert , Spies Marie
Published: April 2022

Epigenetic modifications, such as DNA methylation, are understood as an intermediary between environmental factors affecting disease risk and pathophysiologic changes to brain structure and function. Cerebral monoamine oxidase A (MAO-A) levels are altered in depression, as are DNA methylation levels within theMAOAgene, particularly in the promoter / exon I / intron I region. An effect ofMAOAmethylation on peripheral protein expression was shown, but the extent to which methylation affects brain MAO-A levels is not fully understood. Here, the influence of average and CpG site-specificMAOApromoter / exon I / intron I region DNA methylation on global MAO-A distribution volume (VT), an index of MAO-A density, was assessed via [11C]harmine positron emission tomography in 22 patients suffering from winter-type seasonal affective disorder and 30 healthy controls. No significant influence ofMAOADNA methylation on global MAO-A VTwas found, despite correction for health status (patients vs. controls), sex, season (methylation analysis in spring / summer vs. fall / winter) andMAOAvariable number of tandem repeat genotype (VNTR; high vs. low expression groups). However, in female subjects, season affected average DNA methylation, with higher levels in spring and summer (puncorr= 0.03). We thus did not find evidence for an effect ofMAOADNA methylation on brain MAO-A VT. In contrast to a previous study that demonstrated an effect of the methylation of aMAOApromoter region located further 5’ on brain MAO-A, in the present studyMAOAmethylation appears to affect brain protein levels to a limited extent. The observed effect of season on methylation levels is in accordance with extensive evidence for seasonal effects within the serotonergic system.

Clinicaltrials.govIdentifier

NCT02582398

EUDAMED Number

CIV-AT-13-01-009583
No woman should be left behind: A decomposition analysis of socioeconomic inequalities in unsafe abortion among women presenting for abortion care services in Lusaka and Copperbelt provinces of Zambia
Authors: Kaonga Patrick , Mukosha Moses , Jacobs Choolwe , Munakampe Margarate Nzala , Sichone Victor , Phiri Christabel Chigwe , Makasa Musonda , Vwalika Bellington , Lubeya Mwansa Ketty
Published: April 2022

This study measured socioeconomic-related unsafe abortion inequality among women presenting for abortion care services in Lusaka and the Copperbelt provinces of Zambia and decompose its causes. We conducted a cross-sectional study between August and September 2021. Unsafe abortion inequalities were assessed using corrected concentration index and Erreygers-type decomposition analysis was conducted to assess causes of unsafe abortion inequalities. Out of 362 women, the magnitude of unsafe abortion was 77(21.3%, [95% CI: 17.8, 24.9]). The corrected concentration index was -0.231 (95% CI: -0.309, -0.154), implying pro-poor inequality in unsafe abortion among women. Decomposition analysis showed that the major contributors of the unsafe abortion inequality were socioeconomic status (66.6%), marital status (6.3%), education (10.2%) and employment (3.7%). Also, history of unwanted pregnancy (5.1%), awareness of whether abortion is legal in Zambia (8.9%) and awareness that hospitals offered free abortion services (11.3%). The findings suggest that the unsafe abortion is a problem in Zambia and substantial inequality mainly due to socioeconomic factors. Stakeholders and policymakers should consider socioeconomic strategies to reduce unsafe abortion inequality promoting advocacy to increased access to legal safe abortion and use of modern contraceptives so that no woman is left behind in the prevention of unsafe abortion.
Double burden of malnutrition and its social disparities among rural Sri Lankan adolescents
Authors: Goonapienuwala B. L. , Kalupahana N. S. , Agampodi S. B. , Siribaddana S.
Published: April 2022

In Sri Lanka, the double burden of nutrition is often neglected, and increase of adolescent obesity is not well investigated. This study determines the double burden of malnutrition among adolescents in Anuradhapura district exploring the differences of prevalence based on different definitions. Students aged 13 to 16 years were selected from 74 schools using probability proportionate to size sampling. Anthropometry was done according to WHO guidelines. Obesity was defined according to body mass index (BMI) based definitions of WHO, International Obesity Task Force and Indian growth references. Central obesity was defined using Indian and British waist circumference cut-offs. Prevalence estimates from different definitions were compared using McNemar’s test. Socio-demographic determinants of nutritional issues were assessed using Chi-square test for independence. A total of 3105 students (47.7% boys) were studied (mean age 14.8+ 0.8 years). According to WHO definitions, 73 (2.4%, 95% CI; 1.9–2.9) were obese, 222 (7.2%, 95% CI; 6.3–8.1) were overweight, 673 (21.7%, 95% CI; 20.2–23.1,) were thin and 396 (12.8%, 95% CI; 11.6–14.0) were stunted. More boys (3.1%) than girls (1.7%) were obese as well as thin (29.0% compared to 15.0%). Prevalence of overweight/obesity was higher among students in larger, urban schools, and belonging to high social class and more educated parents. Prevalence of overweight/obesity estimated using IOTF-Asian and Indian thresholds were significantly higher than that from WHO and IOTF-international thresholds. Double burden of malnutrition is affecting the adolescents in rural Sri Lanka. Prevalence estimates of obesity largely depend on the definition used.
Adapted “Break The Cycle for Avant Garde” Intervention to Reduce Injection Assisting and Promoting Behaviours in People Who Inject Drugs in Tallinn, Estonia: A Pre- Post Trial
Authors: Uusküla A , Raag M , Barnes DM , Tross S , Talu A , Des Jarlais D
Published: April 2022

In the context of established and emerging injection drug use epidemics, there is a need to prevent and avert injection drug use. We tested the hypothesis that an individual motivation and skills building counselling, adapted and enhanced from Hunt’s Break the Cycle intervention targeting persons currently injecting drugs would lead to reduction in injection initiation-related behaviours among PWID in Tallinn, Estonia. For this quasi-experimental study, pre-post outcome measures included self-reported promoting behaviours (speaking positively about injecting to non-injectors, injecting in front of non-injectors, offering to give a first injection) and injection initiation behaviours (assisting with or giving a first injection) during the previous 6 months. Of 214 PWID recruited, 189 were retained (88.3%) for the follow-up at 6 months. The proportion of those who had injected in front of non-PWID significantly declined from 15.9% to 8.5%, and reporting assisting with 1st injection from 6.4% to 1.06%. Of the current injectors retained in the study, 17.5% reported not injecting drugs at the follow up. The intervention adapted for the use in the setting of high prevalence of HIV and relatively low prevalence of injection assisting, tested proved to be effective and safe.
Delineating the heterogeneity of preimplantation development via unsupervised clustering of embryo candidates for transfer using automated, accurate and standardized morphokinetic annotation
Authors: Zabari Nir , Kan-Tor Yoav , Or Yuval , Shoham Zeev , Shofaro Yoel , Richter Dganit , Har-Vardi Iris , Ben-Meir Assaf , Srebnik Naama , Buxboim Amnon
Published: April 2022

The majority of human embryos, whether naturally or in vitro fertilized (IVF), do not poses the capacity to implant within the uterus and reach live birth. Hence, selecting the embryos with the highest developmental potential to implant is imperative for improving pregnancy rates without prolonging time to pregnancy. The developmental potential of embryos can be assessed based on temporal profiling of the discrete morphokinetic events of preimplantation development. However, manual morphokinetic annotation introduces intra- and inter-observer variation and is time-consuming. Using a large clinically-labeled multicenter dataset of video recordings of preimplantation embryo development by time-lapse incubators, we trained a convolutional neural network and developed a classifier that performs fully automated, robust, and standardized annotation of the morphokinetic events with R-square 0.994 accuracy. To delineate the morphokinetic heterogeneity of preimplantation development, we performed unsupervised clustering of high-quality embryo candidates for transfer, which was independent of maternal age and blastulation rate. Retrospective comparative analysis of transfer versus implantation rates reveals differences between embryo clusters that are distinctively marked by poor synchronization of the third meiotic cell-cleavage cycle. We expect this work to advance the integration of morphokinetic-based decision support tools in IVF treatments and deepen our understanding of preimplantation heterogeneity.
The predictive significance of prognostic nutritional index and serum albumin/globulin ratio on the overall survival of penile cancer patients undergoing penectomy
Authors: Song Wei-Jie , Li Ni Chu-Jie , Gao Jun , Xu Zhi-Peng , Liu Jian-Ye , Long Zhi , He Le-Ye
Published: April 2022

Objective

To assess the value of using the prognostic nutritional index (PNI) and serum albumin/globulin ratio (AGR) in predicting the overall survival (OS) of patients with penile cancer (PC) undergoing penectomy.

Materials and methods

A retrospective analysis of 123 patients who were admitted to our hospital due to PC from April 2010 to September 2021 and underwent penectomy were included in the study. The optimal cut-off value of PNI and AGR was determined by receiver operating characteristic curve analysis. Kaplan-Meier analysis and the Cox proportional hazard model were used to evaluate the correlation between PNI, AGR, and OS in patients with PC.

Results

The best cut-off values of PNI and AGR were set to 49.03 (95% confidence interval 0.705-0.888, Youden index=0.517, sensitivity=57.9%, specificity=93.7%, P<0.001) and 1.28 (95% confidence interval 0.610-0.860, Youden index=0.404, sensitivity=84.1%, specificity=56.2%, P=0.003). Kaplan-Meier analysis showed that the OS of the patients in the high PNI group and the high AGR group was significantly higher than that of the patients in the low PNI group and the low AGR group (P<0.001). Univariate analysis showed that patient age, clinical N stage, pathological stage, PNI, and SII are all predictors of OS in patients with PC (P<0.05). Multivariate analysis showed that pathological stage (P=0.005), PNI (P=0.021), and AGR (P=0.004) are independent prognostic factors for predicting OS in patients with PC undergoing penectomy.

Conclusions

Both PNI score and serum AGR are independent prognostic factors for predicting OS in patients with PC undergoing penectomy.
Dupilumab use is associated with protection from COVID-19 mortality: A retrospective analysis
Authors: Donlan A. , Mallawaarachchi I. , Sasson J. , Preissner R. , Loomba J. , Petri W.A.
Published: April 2022

We previously found that type 2 immunity promotes COVID-19 pathogenesis in a mouse model. To test relevance to human disease we used electronic health record databases and determined that patients on dupilumab (anti-IL-4Rα monoclonal antibody that blocks IL-13 and IL-4 signaling) at the time of COVID-19 infection had lower mortality.
Sleep problems effect on developmental trajectories in children with autism
Authors: Levin Jonah , Khokhlovich Edward , Vyshedskiy Andrey
Published: April 2022

The effect of sleep problems in 2-to 5-year-old children with ASD was investigated in the largest and the longest observational study to-date. Parents assessed the development of 7069 children quarterly for three years on five orthogonal subscales: receptive language, expressive language, sociability, sensory awareness, and health. Moderate and severe sleep problems were reported in 13% of children. Children with no sleep problems developed faster compared to matched children with sleep problems in all subscales. The greatest difference in trajectories was detected in the health subscale. When controlling for the health score (in addition to each subscale score at baseline as well as gender and severity), the effect of sleep problems decreased in all subscales except the combinatorial receptive language subscale (where the effect of sleep problems was increased), suggesting that sleep problems affect combinatorial language acquisition irrespective of the overall health. This study confirms a high prevalence of sleep problems in ASD children and points to the need for more systematic research as an initial step in developing treatment strategies.
Behaviour change interventions improve maternal and child nutrition in sub-Saharan Africa: a systematic review
Authors: Watson Daniella , Mushamiri Patience , Beeri Paula , Rouamba Toussaint , Jenner Sarah , Kehoe Sarah H , Ward Kate A , Barker Mary , Lawrence Wendy ,   the INPreP Study Group
Published: April 2022

Background

Evidence that nutrition-specific and nutrition-sensitive interventions can improve maternal and child nutrition status in sub-Saharan Africa is inconclusive. Using behaviour change theory and techniques in intervention design may increase effectiveness and make outcomes more predictable. This systematic review aimed to determine whether interventions that included behaviour change functions were effective.

Methods

Six databases were searched systematically, using MeSH and free-text terms, for articles describing nutrition-specific and nutrition-sensitive behaviour change interventions published in English until January 2022. Titles, abstracts and full-text papers were double-screened. Data extraction and quality assessments followed Centre for Reviews and Dissemination guidelines. Behaviour change functions of interventions were mapped onto the COM-B model and Behaviour Change Wheel. PROSPERO registered (135054).

Findings

The search yielded 1149 articles: 71 articles met inclusion criteria, ranging from low (n=30) to high (n=11) risk of bias. Many that applied behaviour change theory, communication or counselling resulted in significant improvements in infant stunting and wasting, household dietary intake and maternal psychosocial measures. Interventions with >2 behaviour change functions (including persuasion, incentivisation, environmental restructuring) were the most effective.

Interpretation

We recommend incorporating behaviour change functions in nutrition interventions to improve maternal and child outcomes, specifically drawing on the Behaviour Change Wheel, COM-B model. To enhance the designs of these interventions, and ultimately improve the nutritional and psychosocial outcomes for mothers and infants in sub-Saharan Africa, collaborations are recommended between behaviour change and nutrition experts, intervention designers, policy makers and commissioners to fund and roll-out multicomponent behaviour change interventions.
COVID-19 in people with neurofibromatosis 1, neurofibromatosis 2, or schwannomatosis
Authors: Banerjee Jineta , Friedman Jan M. , Klesse Laura J. , Yohay Kaleb ,   Children’s Tumor Foundation Clinical Care Advisory Board, Jordan Justin T , Plotkin Scott , Allaway Robert J , Blakeley Jaishri
Published: April 2022

Purpose

People with pre-existing conditions may be more susceptible to severe Coronavirus disease 2019 (COVID-19) when infected by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The relative risk and severity of SARS-CoV-2 infection in people with rare diseases like neurofibromatosis (NF) type 1 (NF1), neurofibromatosis type 2 (NF2), or schwannomatosis (SWN) is unknown.

Methods

We investigated the proportions of SARS-CoV-2 positive or COVID-19 patients in people with NF1, NF2, or SWN in the National COVID Collaborative Cohort (N3C) electronic health record dataset.

Results

The cohort sizes in N3C were 2,501 (NF1), 665 (NF2), and 762 (SWN). We compared these to N3C cohorts of other rare disease patients (98 - 9844 individuals) and the general non-NF population of 5.6 million. The site- and age-adjusted proportion of people with NF1, NF2, or SWN who tested positive for SARS-CoV-2 or were COVID-19 patients (collectively termed positive cases) was not significantly higher than in individuals without NF or other selected rare diseases. There were no severe outcomes reported in the NF2 or SWN cohorts. The proportion of patients experiencing severe outcomes was no greater for people with NF1 than in cohorts with other rare diseases or the general population.

Conclusion

Having NF1, NF2, or SWN does not appear to increase the risk of being SARS-CoV-2 positive or of being a COVID-19 patient, or of developing severe complications from SARS-CoV-2.
Emulation of epidemics via Bluetooth-based virtual safe virus spread: experimental setup, software, and data
Authors: Asanjarani Azam , Shausan Aminath , Chew Keng , Graham Thomas , Henderson Shane G. , Jansen Hermanus M. , Short Kirsty R. , Taylor Peter G. , Vuorinen Aapeli , Yadav Yuvraj , Ziedins Ilze , Nazarathy Yoni
Published: April 2022

We describe an experimental setup and a currently running experiment for evaluating how physical interactions over time and between individuals affect the spread of epidemics. Our experiment involves the voluntary use of the Safe Blues Android app by participants at The University of Auckland (UoA) City Campus in New Zealand. The app spreads multiple virtual safe virus strands via Bluetooth depending on the social and physical proximity of the subjects. The evolution of the virtual epidemics is recorded as they spread through the population. The data is presented as a real-time (and historical) dashboard. A simulation model is applied to calibrate strand parameters. Participants’ locations are not recorded, but participants are rewarded based on the duration of participation within a geofenced area, and aggregate participation numbers serve as part of the data. Once the experiment is complete, the data will be made available as an open-source anonymized dataset.

This paper outlines the experimental setup, software, subject-recruitment practices, ethical considerations, and dataset description. The paper also highlights current experimental results in view of the lockdown that started in New Zealand at 23:59 on August 17, 2021. The experiment was initially planned in the New Zealand environment, expected to be free of COVID and lockdowns after 2020. However, a COVID Delta strain lockdown shuffled the cards and the experiment is currently extended into 2022.

Author summary

In this paper, we describe the Safe Blues Android app experimental setup and a currently running experiment at the University of Auckland City Campus. This experiment is designed to evaluate how physical interactions over time and between individuals affect the spread of epidemics.

The Safe Blues app spreads multiple virtual safe virus strands via Bluetooth based on the subjects’ unobserved social and physical proximity. The app does not record the participants’ locations, but participants are rewarded based on the duration of participation within a geofenced area, and aggregate participation numbers serve as part of the data. When the experiment is finished, the data will be released as an open-source anonymized dataset.

The experimental setup, software, subject recruitment practices, ethical considerations, and dataset description are all described in this paper. In addition, we present our current experimental results in view of the lockdown that started in New Zealand at 23:59 on August 17, 2021. The information we provide here may be useful to other teams planning similar experiments in the future.
Effect of vaccination rates on the prevalence and mortality of COVID-19
Authors: Westerhout Jacob , Khataee Hamid , Neufeld Zoltan
Published: April 2022

By looking at trends in global epidemic data, we evaluate the effectiveness of vaccines on the incidence and mortality from the delta variant of COVID-19. By comparing countries of varying vaccination levels, we find that more vaccinated countries have lower deaths while not having lower cases. This cannot be explained by testing rates or restrictions, but can be partly explained by the most susceptible countries also being the highest vaccinated countries. We also find that during the period when many countries have high vaccination rates, cases and deaths are both increasing in time. This seems to be caused by the waning of the protection vaccines grant against infection.