bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the gender gap in welfare attitudes: relational skills and perceptions of pay equity
Authors: Hwang In Hyee , Lim Hyunji , Lee Cheol-Sung
Published: October 2022

This article introduces a new aspect of skill profiles, ‘relational skills’, to examine how occupation-oriented relational skills can activate different perceptions of pay equity between genders and influence support for the welfare state. Relational skills refer to the degree of which a worker possesses skills pertaining to human interactions to those regarding the operation of machines or tools. We examine how relational skill ratio differently influences perceptions of justice in the pay system for men and women and how this shapes their welfare attitudes. By analyzing levels of support for redistribution in 30 OECD member countries targeted by the International Social Survey Program in 2009, we find the gender divide in social policy preferences to be the widest in high relational skill occupations. We argue that this divide is associated with the significant contrast between men and women in whether they perceive their pay to justly reflect their efforts and skills. Our findings suggest that women’s perceptions of discriminatory wage scales and support for the welfare state will be most prominent in occupations that present evaluation ambiguities or gender ascriptions that challenge women from breaking the glass ceiling.
Early pregnancy serum levels of folate and vitamin B12 in overweight and obese women in Khartoum, Sudan
Authors: Rayis Duria A , Karar Ahmed , Alshareef Shimos A , Eltayeb Reem , Adam Ishag
Published: October 2022

Background

This study was conducted to assess serum levels of folate and vitamin B12 in overweight and obese pregnant women.

Methods

A cross-sectional study was conducted at Saad Abualila Hospital, Sudan. Clinical data were collected through questionnaires and body mass index (BMI) was computed from weight and height. The serum folate and vitamin B12 levels were analyzed by immunofluorescence.

Results

Of 300 enrolled women, 44.7% were of normal weight, 32.3% were overweight and 3.0% were obese. The folate level was significantly lower in overweight women (median 4.79 ng/ml [IQR 2.70‒7.70]) than in normal-weight women (median 6.650 ng/ml [IQR 3.30‒10.55]; p=0.022). There was no significant difference in the prevalence of marginal and severe folate deficiencies in women in different BMI groups. Compared with normal-weight women (median 197.5 pg/ml [IQR 150.0‒263.0]), obese women (median 173.0 pg/ml [IQR 150.0‒213.0]; p=0.038) had significantly lower vitamin B12 levels and had a higher prevalence of vitamin B12 insufficiency. Fair negative correlations (p<0.01) were observed between folate and BMI (r = −0.157) and between vitamin B12 and BMI (r = −0.173).

Conclusions

Overweight and obese pregnant Sudanese women had lower levels of serum folate and vitamin B12.
Assessing the productivity of PAs and NPs
Authors: Stefos Theodore , Moran Eileen A. , Poe Stacy A. , Hooker Roderick S.
Published: October 2022

The improvement of healthcare efficiency and productivity is of international interest. Following an expansion phase of physician associate/assistant (PA) and NPs employment, the Department of Veterans Affairs (VA) assessed how and where they were being used. Using data from 134 VA medical centers, annual productivity was examined across 30 medical and surgical specialties spanning primary care, mental health, and surgery. PA productivity differences averaged 82 relative value units per full-time employee per year more than NPs, a difference of 4%. In general, PAs were found in higher productivity ranges than NP counterparts. PAs and NPs have statistically similar productivity levels in primary care and mental health. In specialty medicine and surgery, PAs average higher annual productivity than NPs. This analysis provides some utility for managers regarding workforce composition, given the relative productivity of two types of clinicians.
Comparison of a Novel Modified All-Suture Construct versus Suspensory Suture-button Fixation in a Syndesmotic Injury Model
Authors: Baker Hayden P. , Muriuki Muturi G. , Straszewski Andrew J. , Johnson Christopher , Krishnan Pranav , Hynes Kelly , Strelzow Jason A. , Havey Robert M. , Dillman Daryl B.
Published: October 2022

Objectives:

To biomechanically investigate a novel modified all-suture construct compared with commercially available suspensory button fixation for stabilization of the syndesmosis.

Methods:

Eight matched pairs of cadaver lower limbs were obtained. We used a material testing machine and Optotrak optoelectronic 3D motion measurement system for testing. Syndesmotic injuries were simulated, and specimens were fixed with either a suspensory suture button or modified all-suture construct. Repaired specimens were then cyclically loaded for 500 cycles. Spatial relationship of the tibia and fibula were continuously monitored for the intact, destabilized, and repaired states. The results were analyzed using independent samples t test.

Results:

There was no significant difference in sagittal or coronal plane translation between intact and either repair. Compared with the intact state, both repair techniques demonstrated significantly more external rotation of the fibula relative to the tibia and decreased construct stiffness. Cycling of the specimens did not significantly increase coronal or sagittal plane translation; however, external rotation of the fibula relative to the tibia increased and stiffness decreased with cycling for both repair techniques.

Conclusions:

Our data suggest that sagittal and coronal plane translation is no different from the intact state for both fixation techniques. However, rotation of the fibula relative to the tibia was increased, and construct stiffness was decreased compared with the intact state for both fixation techniques. These findings suggest that an all-suture construct could offer syndesmotic fixation comparable with proprietary suspensory button fixation in a cadaver model.
Porcine Model of Acute Compartment Syndrome
Authors: Honjol Yazan , Monk Rachel , Schupbach Drew , Merle Geraldine , Harvey Edward J.
Published: October 2022

Objectives:

Acute compartment syndrome is a devastating condition associated with lasting consequences or even death if not treated in a timely fashion. Current preclinical modeling is inadequate. Ideally a model should mimic human disease. There should be a trauma-induced reperfusion or direct muscle event that causes gradual increased pressure and is amenable to release with fasciotomy. We have attempted to reproduce this mechanism and outcome in a porcine model.

Methods:

Anterior tibial musculature was injured with vascular occlusion plus exterior tourniquet crush or direct intracompartmental crush through balloon inflation. The injury was maintained for over 5 hours. At that time, the tourniquet or balloon was removed. The injuries were continuously monitored with an intramuscular continuous pressure sensor. Pressure changes were recorded and after 2 hours of postinjury observation, a fasciotomy was performed for the muscle compartment.

Results:

Pressures were brought to 100 mm Hg during the injury phase. During the two-hour observation period, the balloon catheter technique achieved an average pressure of 25.1 ± SD 8.8 mm Hg with a maximum reading of 38.2 mm Hg and minimum reading of 14.1 mm Hg. During this same period, the ischemia-reperfusion + direct crush technique achieved an average pressure of 33.7 ± SD 7.3 mm Hg, with a maximum reading of 43.5 mm Hg and minimum reading of 23.5 mm Hg. Average pressure postfasciotomy for the balloon catheter technique was 2.4 ± SD 2.5 mm Hg; and for the crush technique, average value postfasciotomy was 4.9 ± SD 3.7 mm Hg—both representing a return to physiologic levels.

Conclusion:

This is the first preclinical model that shows the same response to injury and treatment as is observed in human physiology. Surgical and nonsurgical therapies for compartment syndrome can now be tested reliably.
Associations of Reproductive Health Concerns, Health-Related Quality of Life, and Stress Among Adolescents and Young Adults with Chronic Illness
Authors: Iverson Ellen , Brammer Whitney A. , Osorio Brenda , Tanaka Diane , Cuevas Rachel
Published: October 2022

Objective:

Adolescents and young adults (AYA) living with chronic illness are as sexually active and interested in having children as healthy peers. Few studies have examined the intersection of managing chronic illness and concerns about realizing reproductive goals, including fertility, pregnancy, childbirth, and parenting. Even less is understood regarding how these concerns might be associated with psychological distress. This study examines associations between the reproductive health concerns (RHC) and health-related stress of AYA patients living with chronic conditions including rheumatologic, cardiac, pulmonology, gastrointestinal disorders, and solid organ transplant.

Methods:

A total of 140 patients aged 15 to 20 years (68% female; 81% Hispanic/Latinx) recruited from a transition program located at a safety-net pediatric institution completed surveys examining multiple dimensions of RHC and health-related quality of life (life satisfaction, illness burden, and illness-related anxiety) and condition-related stress. Exploratory factor analyses of RHC variables yielded 3 factors used in regression analyses to identify convergent validity of RHC factors with health-related mental health measures.

Results:

Three RHC factor loadings emerged: concern about availability to raise children (timing/future), impact of condition/medication on fertility and childbearing (pregnancy/fertility), and impact of condition on motivation to have children (motivation/decision-making). Positive associations were found between all RHC factors and illness-related anxiety; condition-related stress was associated with motivation/decision-making.

Conclusion:

RHC, health-related anxiety, and stress can impede healthy sexual and reproductive health and development of AYA living with chronic conditions. Providers' proactive exploration of patients' concerns about their reproductive future can offer critical support as they navigate the unique existential challenges of early adulthood.
Research Gaps in Fragile X Syndrome: An Updated Literature Review to Inform Clinical and Public Health Practice
Authors: Raspa Melissa , Wheeler Anne , Okoniewski Katherine C. , Edwards Anne , Scott Samantha
Published: October 2022

Objective:

The phenotypic impact of fragile X syndrome (FXS) has been well-documented since the discovery of the fragile X messenger ribonucleoprotein 1 gene 30 years ago. However, gaps remain in clinical and public health research. The purpose of this literature review was to determine the extent to which these gaps have been addressed and identify targeted areas of future research.

Methods:

We conducted an electronic search of several scientific databases using a variety of key words. The search focused on 5 areas identified as research gaps by an earlier review: (1) diagnosis, (2) phenotypic presentation, (3) familial impact, (4) interventions and treatments, and (5) life span perspectives. Inclusion criteria included publication between 2014 and 2020, focus on human subjects, and publication in English. A total of 480 articles were identified, 365 were reviewed, and 112 are summarized in this review.

Results:

Results are organized into the following categories: (1) FXS phenotype and subtypes (FXS subtypes, medical profile, cognitive/developmental profile, social and behavioral profile); (2) needs of adults; (3) public health needs (clinical diagnosis and newborn screening, health care needs, and access); (4) treatment (treatment priorities, pharmacological treatments, and behavioral and educational interventions); and (5) families (economic burden and mother-child relationship).

Conclusion:

Despite the progress in many areas of FXS research, work remains to address gaps in clinical and public health knowledge. We pose 3 main areas of focused research, including early detection and diagnosis, determinants of health, and development and implementation of targeted interventions.
The Majority of Venous Thromboembolism Events Should Occur in Lower Risk Aesthetic Surgery Patients: A Simulation Study
Authors: Pannucci Christopher J. , Momeni Arash , Januszyk Michael
Published: October 2022

Introduction:

Evidence-based venous thromboembolism (VTE) prevention among aesthetic patients is lacking. This study seeks to (1) quantify 2005 Caprini scores in primary breast augmentation patients, (2) determine the proportion of patients with potentially modifiable VTE risk factors, and (3) project, using Monte Carlo simulation, the expected distribution of Caprini scores among aesthetic surgery patients who develop VTE.

Methods:

The observational study (part 1) screened consecutive primary breast augmentation patients for VTE risk using the 2005 Caprini score. Aggregate scores were compiled, and the proportion of patients with potentially modifiable risk factors were identified. Part 2 used Monte Carlo simulation to generate risk score distributions for VTE events predicted to occur among randomly sampled patient cohorts with baseline Caprini risk profiles derived from the part 1 data.

Results:

One hundred patients had mean age of 35.7 years and mean body mass index of 23.8 kg/m2. Median 2005 Caprini score was 3 (range, 2–8), with the majority (96%) having scores of ≤6. Twenty-eight percent of patients had at least one potentially modifiable risk factor or risk factor potentially benefiting from further investigation. Monte Carlo simulations demonstrated that for a population with 96% Caprini ≤6 (and 4% Caprini ≥7), 80% of VTE events would be expected to occur in patients with Caprini scores ≤6.

Conclusions:

The majority of breast augmentation patients in this study (96%) have 2005 Caprini scores ≤6. Twenty-eight percent of patients have potentially modifiable risk factors. The majority of patients with VTE after aesthetic surgery are expected to have lower Caprini risk scores.
The Transverse Facial Artery as a Recipient Artery in Neuroplastic Surgery Microvascular Reconstruction
Authors: Tunyi Jude , Huayllani Maria T. , Skoracki Roman , Mitchell Kerry-Ann S.
Published: October 2022

Microvascular reconstruction in the craniofacial region is particularly challenging due to a paucity of adequate recipient vessels. The facial vessels are commonly utilized; however, in neurocranial reconstruction, the distance from the defect to the vessels may require the use of interposition vein grafts. The superficial temporal vessels, which have the benefit of closer proximity, are often compromised or injured in patients with previous neurosurgical procedures or radiation therapy. Here, we describe the use of the transverse facial artery as a recipient for a latissimus dorsi free flap for scalp reconstruction in a 63-year-old man with a compromised scalp from multiple surgeries and radiation therapy for glioblastoma multiforme. The patient had extensive scarring, temporalis muscle wasting, thinning of the overlying scalp, and notable alopecia. On surveillance imaging, he was found to have an area on the brain concerning for tumor recurrence, for which a surgical biopsy was recommended, with a significant risk of postoperative wound healing complications. We present the use of the transverse facial artery in this case as a recipient artery for free flap reconstruction of the scalp.
HPV Vaccination Initiation and Completion Among Pediatric, Adolescent, and Young Adult Cancer Survivors and a Comparison Population Sample Receiving Primary Care
Authors: Kaddas Heydon K. , Ramsay Joemy M. , Ou Judy Y. , Fair Douglas , Kepka Deanna , Kirchhoff Anne C.
Published: October 2022

Human papillomavirus (HPV) vaccinations can reduce pediatric, adolescent, and young adult (PAYA) cancer survivors’ susceptibility to HPV-related subsequent cancers. We examined differences in HPV vaccination initiation and completion among a Utah-based cohort of PAYA cancer survivors and a cancer-free population sample. Participants received primary care at 1 of 2 health care systems during study follow-up: 2006-2016. Vaccination records were identified from these health care systems, statewide vaccination records, and an all-payer claims database. HPV vaccination initiation (1 dose) and completion (3 doses) were compared between cancer survivors (N=1579) and age-matched and sex-matched cancer-free population sample (N=4513). Individuals were aged 9 to 21 years at cohort entry. Mixed-effects Poisson regression estimated incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Relative to the population sample, cancer survivors were less likely to initiate vaccination (IRR=0.8, 95% CI: 0.73-0.98). The most severe disparity compared with the population sample for vaccine initiation (IRR=0.5, 95% CI: 0.31-0.74) or completion (IRR=0.5, 95% CI: 0.28-0.89) was observed for Hispanic survivors. PAYA cancer survivors are less likely to initiate HPV vaccination series than noncancer counterparts. Targeted interventions should be directed at PAYA survivors to raise HPV vaccination with emphasis on high-risk groups such as Hispanic survivors.
The Use of Extracorporeal Membrane Oxygenation as a Bridge to Bone Marrow Transplantation in a Patient With High-risk Acute Myeloid Leukemia
Authors: Nader Marie , Bonde Pramod , Massaro Stephanie , Giuliano John S. , Shah Niketa
Published: October 2022

An 18-year-old girl with high-risk acute myeloid leukemia developed Streptococcus mitis septic shock and multiorgan dysfunction syndrome, including biventricular failure. Due to the anticipated reversibility of her cardiogenic shock, her young age, and her favorable survival chance after an allogeneic hematopoietic stem cell transplant, she was placed on full circulatory support with venoarterial extracorporeal membrane oxygenation as a bridge to her successful hematopoietic stem cell transplantation 2 months later. This highlights the importance of prognostication in patient selection for extracorporeal life support. A multidisciplinary approach is essential to each case until more definite initiation criteria, risk stratification, and treatment protocols are established.
Virtual Surgical Planning and 3-Dimensional Printing for the Treatment of Zygomaticomaxillary Complex and/or Orbital Fracture
Authors: Abdul Lateef Hassan Thair , Abbood Mohammed Dunia
Published: October 2022

Background:

Traditionally, in zygomaticomaxillary complex and orbital fractures, miniplates and titanium orbital mesh are used and adapted intraoperatively, which may cause fatigue of the metal and increase the surgical time. Recently, computer-assisted surgery and 3-dimensional printing enable the surgeon to employ 3-dimensional segmentation and mirroring tools, which mimic the pretraumatized anatomy on which the miniplates and titanium orbital mesh are preoperatively molded to precisely duplicate the orbital volume, enophthalmos, and zygomatic bone position.

Aim:

To evaluate the results of computer technology using 3-dimensional printing model to prebend miniplates and titanium orbital mesh in the restoration of orbital volume, enophthalmos, and zygomatic bone position in the initial management of patients with zygomaticomaxillary complex and/or orbital fractures.

Patients and Methods:

This prospective clinical study included 10 Iraqi male patients who met the eligibility criteria and subjected to open reduction and internal fixation utilizing virtual surgical planning and a 3-dimensional model to prebend miniplates and titanium orbital mesh as a treatment modality for facial fractures. The data were analyzed according to the orbital volume, enophthalmos, zygomatic bone position, age, gender, etiology of the fracture, and complications. The patients were radiographically followed up with a computed tomography scan at 4 months postoperatively. The statistical analysis was performed using percentages, the mean±SD, Shapiro–Wilk test, Paired t test, One Way Anova, and Independent t test.

Results:

The age of the patients ranged from 18 to 66 years, with an average of 28.6 years and a SD of±14.5 years. Regarding gender, all patients were males. By utilizing virtual surgical planning and 3-dimentional model to prebend miniplates and titanium orbital mesh and concerning the fracture types, which include the zygomaticomaxillary complex, orbital, and combined fractures, there was no significant difference between the measurement of intact side and 4 months postoperatively in orbital volume, enophthalmos, and zygomatic bone position (P >0.05).

Conclusion:

This study demonstrated that computer-aided techniques, virtual planning, and the use of prebend miniplates and titanium orbital mesh enable anatomically precise reduction and fixation of the orbital, zygomaticomaxillary complex, and combined fractures regarding orbital volume, enophthalmos, and zygomatic bone position.
Computer-based Eye-tracking Analysis of King-Devick Test Differentiates Persons With Idiopathic Normal Pressure Hydrocephalus From Cognitively Unimpaired
Authors: Lehtola Juha-Matti , Kärkkäinen Virve , Andberg Sami , Hannonen Sanna , Rusanen Minna , Saari Toni , Korhonen Ville , Hokkanen Laura , Hallikainen Merja , Hänninen Tuomo , Kaarniranta Kai , Bednarik Roman , Leinonen Ville , Koivisto Anne M.
Published: October 2022

Background:

Functional defects in eye movements and reduced reading speed in neurodegenerative diseases represent a potential new biomarker to support clinical diagnosis. We investigated whether computer-based eye-tracking (ET) analysis of the King-Devick (KD) test differentiates persons with idiopathic normal pressure hydrocephalus (iNPH) from cognitively unimpaired [control (CO)] and persons with Alzheimer’s disease (AD).

Methods:

We recruited 68 participants (37 CO, 10 iNPH, and 21 AD) who underwent neurological examination, the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological test battery (CERAD-NB), and a Clinical Dementia Rating interview. The KD reading test was performed using computer-based ET. We analyzed the total time used for the reading test, number of errors, durations of fixation and saccade, and saccade amplitudes.

Results:

The iNPH group significantly differed from the CO group in the KD test mean total time (CO 69.3 s, iNPH 87.3 s; P≤0.009) and eye-tracking recording of the mean saccade amplitude (CO 3.6 degree, iNPH 3.2 degree; P≤0.001). The AD group significantly differed from the CO group in each tested parameter. No significant differences were detected between the iNPH and AD groups.

Conclusion:

For the first time, we demonstrated altered reading ability and saccade amplitudes in patients with iNPH.
Effects of Depression on Changes in Cognitive Function in Older Adults
Authors: Kim Dasom
Published: October 2022

Purpose:

This study identified the rate of change in cognitive function of community-based middle-aged and older adults and investigated the longitudinal effects of depression, health status, and health behavior by cognitive function group [normal, mild cognitive impairment (MCI), dementia] using data from the Korean Longitudinal Study of Aging.

Methods:

This longitudinal panel analysis collected 21,425 data points from 4285 participants. Cognitive function change patterns in the groups were examined through descriptive analysis. A fixed-effects model was estimated using demographic factors, such as depression, health behavior, and disease states as independent variables.

Results:

Compared with the baseline score of the mini-mental state examination (MMSE), the 8-year mean score decreased by 10.51, 8.6, and 1.21 for the dementia, MCI, and normal groups, respectively. The estimates for the normal group showed that an increase in the depression score significantly negatively impacted the MMSE score (B=−0.059, P<0.001). However, compared with those of the MCI group (B=−0.044, P>0.05), the estimates of the dementia group confirmed that depression significantly negatively affected cognitive function (B=−0.146, P<0.05).

Conclusion:

Each group showed different patterns of cognitive decline. An annual follow-up cognitive impairment screening to investigate changes in MMSE score in community-based older individuals can enable early detection of dementia.
A genome-wide mutational constraint map quantified from variation in 76,156 human genomes
Authors: Chen Siwei , Francioli Laurent C. , Goodrich Julia K. , Collins Ryan L. , Kanai Masahiro , Wang Qingbo , Alföldi Jessica , Watts Nicholas A. , Vittal Christopher , Gauthier Laura D. , Poterba Timothy , Wilson Michael W. , Tarasova Yekaterina , Phu William , Yohannes Mary T. , Koenig Zan , Farjoun Yossi , Banks Eric , Donnelly Stacey , Gabriel Stacey , Gupta Namrata , Ferriera Steven , Tolonen Charlotte , Novod Sam , Bergelson Louis , Roazen David , Ruano-Rubio Valentin , Covarrubias Miguel , Llanwarne Christopher , Petrillo Nikelle , Wade Gordon , Jeandet Thibault , Munshi Ruchi , Tibbetts Kathleen ,   gnomAD Project Consortium, O’Donnell-Luria Anne , Solomonson Matthew , Seed Cotton , Martin Alicia R. , Talkowski Michael E. , Rehm Heidi L. , Daly Mark J. , Tiao Grace , Neale Benjamin M. , MacArthur Daniel G. , Karczewski Konrad J.
Published: October 2022

The depletion of disruptive variation caused by purifying natural selection (constraint) has been widely used to investigate protein-coding genes underlying human disorders, but attempts to assess constraint for non-protein-coding regions have proven more difficult. Here we aggregate, process, and release a dataset of 76,156 human genomes from the Genome Aggregation Database (gnomAD), the largest public open-access human genome reference dataset, and use this dataset to build a mutational constraint map for the whole genome. We present a refined mutational model that incorporates local sequence context and regional genomic features to detect depletions of variation across the genome. As expected, proteincoding sequences overall are under stronger constraint than non-coding regions. Within the non-coding genome, constrained regions are enriched for known regulatory elements and variants implicated in complex human diseases and traits, facilitating the triangulation of biological annotation, disease association, and natural selection to non-coding DNA analysis. More constrained regulatory elements tend to regulate more constrained protein-coding genes, while non-coding constraint captures additional functional information underrecognized by gene constraint metrics. We demonstrate that this genome-wide constraint map provides an effective approach for characterizing the non-coding genome and improving the identification and interpretation of functional human genetic variation.
Transmission modeling to infer tuberculosis incidence, prevalence, and mortality in settings with generalized HIV epidemics
Authors: Dodd Peter J. , Shaweno Debebe , Ku Chu-Chang , Glaziou Philippe , Pretorius Carel , Hayes Richard J. , MacPherson Peter , Cohen Ted , Ayles Helen
Published: October 2022

Tuberculosis (TB) killed more people globally than any other single pathogen over the past decade. Where surveillance is weak, estimating TB burden estimates uses modeling. In many African countries, increases in HIV prevalence and antiretroviral therapy (ART) have driven dynamic TB epidemics, complicating estimation of burden, trends, and potential intervention impact. We therefore developed a novel age-structured TB transmission model incorporating evolving demographic and HIV/ART effects, and calibrated to TB prevalence and notification data from 12 African countries. We used Bayesian methods to include uncertainty for all TB model parameters, and estimated age-specific annual risks of TB infection (ARTI) and proportion of TB incidence from recent (re)infection (PR). We found ARTI of up to 16.0%/year in adults, but a mean PR across countries of 34%. Rapid reduction of the unacceptably high burden of TB in high HIV prevalence settings will require interventions addressing progression as well as transmission.
Sexual health knowledge acquisition processes among very young adolescent girls in rural Malawi: Implications for sexual and reproductive health programs
Authors: Chimwaza-Manda Wanangwa , Kamndaya Mphatso , Chipeta Effie Kondwani , Sikweyiya Yandisa
Published: October 2022

Early adolescence is a period characterized by enormous biological, cognitive, sexual, emotional, and social changes. Sexual curiosity and the desire to acquire sexual health (SH) information are part of these developments. Understanding the SH knowledge acquisition process is critical for designing interventions that can best support very young adolescents (VYAs). This study explored the SH knowledge acquisition processes among VYA girls aged 10 to 14 years who attended the DREAMs Girl Only Clubs (GOCs) and those who did not. The GOCs were a part of a larger comprehensive HIV prevention project called DREAMS (Determined,Resilient,Empowered,AIDS-free,Mentored, andSafe) which provided an evidence-based core package of interventions to VYAs to prevent HIV. In-depth interviews were conducted with 43 VYA girls aged 10-14 years in two rural southern districts of Zomba and Machinga in Malawi. Twenty-three VYA girls were GOC participants and 20 VYAs were not. Guided by the Social Ecological Model, a thematic analysis approach was used to analyze the data with the assistance of Nvivo 12 software. The SH knowledge acquisition processes were the interaction of various factors at the microsystem (biological factors, attitudes), mesosystem (parents, older relatives, friends), and exosystem levels (schools and GOCs). Factors influencing this interaction included the beginning of menstruation, supportive parents/adults on SH issues, trust and confidentiality in SH information sources, and preference for well-informed sources of information. Compared to Non-GOC participants, GOC participants demonstrated an in-depth knowledge of SH issues, and positive sexual behaviors such as HIV testing. Limitations to SH knowledge acquisition were adult messages’ focus on sexual relationship avoidance and on girls who have started menstruation; perception of adults not being knowledgeable about SH and school teachers hiding some SH information. VYA SH interventions that provide VYA with accurate SH information such as the GOCs have the potential to address the limitations that other sources have in reaching VYAs. Integrating such interventions with empowering parents, other adults, and teachers with comprehensive SH information and with skills on how to deliver SH information to VYAs can enhance their SH knowledge acquisition and influence positive behavior change.
Influences of rare protein-coding genetic variants on the human plasma proteome in 50,829 UK Biobank participants
Authors: Dhindsa Ryan S. , Burren Oliver S. , Sun Benjamin B. , Prins Bram P. , Matelska Dorota , Wheeler Eleanor , Mitchell Jonathan , Oerton Erin , Hristova Ventzislava A. , Smith Katherine R. , Carss Keren , Wasilewski Sebastian , Harper Andrew R. , Paul Dirk S. , Fabre Margarete A. , Runz Heiko , Viollet Coralie , Challis Benjamin , Platt Adam ,   AstraZeneca Genomics Initiative, Vitsios Dimitrios , Ashley Euan A. , Whelan Christopher D. , Pangalos Menelas N. , Wang Quanli , Petrovski Slavé
Published: October 2022

Combining human genomics with proteomics is becoming a powerful tool for drug discovery. Associations between genetic variants and protein levels can uncover disease mechanisms, clinical biomarkers, and candidate drug targets. To date, most population-level proteogenomic studies have focused on common alleles through genome-wide association studies (GWAS). Here, we studied the contribution of rare protein-coding variants to 1,472 plasma proteins abundances measured via the Olink Explore 1536 assay in 50,829 UK Biobank human exomes. Through a variant-level exome-wide association study (ExWAS), we identified 3,674 rare and significant protein quantitative trait loci (pQTLs), of which 76% were undetected in a prior GWAS performed on the same cohort, and we found that rare pQTLs are less likely to be random in their variant effect annotation. In gene-based collapsing analyses, we identified an additional 166 significant gene-protein pQTL signals that were undetected through single-variant analyses. Of the total 456 protein-truncating variant (PTV)-drivencis-pQTLs in the gene-based collapsing analysis, 99.3% were associated with decreased protein levels. We demonstrate how this resource can identify allelic series and propose biomarkers for several candidate therapeutic targets, includingGRN, HSD17B13, NLRC4, and others. Finally, we introduce a new collapsing analysis framework that combines PTVs with missensecis-pQTLs that are associated with decreased protein abundance to bolster genetic discovery statistical power. Our results collectively highlight a considerable role for rare variation in plasma protein abundance and demonstrate the utility of plasma proteomics in gene discovery and unravelling mechanisms of action.
Immune response after SARS-CoV-2 infection with residual post COVID symptoms
Authors: Pongkunakorn Tanyaporn , Manosan Thamonwan , Surawit Apinya , Ophakas Suphawan , Mongkolsucharitkul Pichanun , Pumiem Sureeporn , Suta Sophida , Pinsawas Bonggochpass , Sookrung Nitat , Saelim Nawannaporn , Mahasongkram Kodchakorn , Prangtaworn Pannathee , Tungtrongchitr Anchalee , Tangjittipokin Watip , Boonnak Kobporn , Narkdontri Tassanee , Teerawattanapong Nipaporn , Jongkaewwattana Anan , Mayurasakorn Korapat
Published: October 2022

BACKGROUND

In a number of patients, post-acute COVID syndrome develops after acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Long COVID [LC]). Here, we examined the immune responses and clinical characteristics of individuals with LC compared to age- and gender-matched healthy recovered COVID individuals (HC) during the Omicron pandemic. Immune responses following BNT162b2 (Pfizer) booster are also determined.

METHODS

This retrospective cohort study included 292 patients (LC, 158; HC, 134) confirmed to have SARS-CoV-2 infection from January to August 2022. We determined anti-SARS-CoV-2 receptor-binding domain immunoglobulin G (anti-RBD IgG), surrogate virus neutralization test (sVNT), T-cell subsets, and neutralization of wild-type, BA.1 and BA.5. A subset of patients was voluntarily recruited for booster vaccination with BNT162b2 vaccine and immunogenicity was assessed 4weeks after vaccination.

RESULTS

Cycle thresholds were higher in the HC group than in the LC group (20.7 vs. 19.7; P<0.039). Anti-RBD IgG was higher at ≤56 days after COVID-19 onset (PC) in 3-dose vaccines compared with 2-dose vaccines in the LC group (P=0.02) and after 57-84 days PC in 3-dose vaccines in the HC group (P<0.001). The sVNT in LC was significantly high against Wuhan and sVNT was 30% lower against the Omicron than the Wuhan. sVNT was relatively sustained in 3-dose vaccines than ≤ 2-dose vaccines. sVNT in the HC group reached its peak at 57-84 days PC as compared with the LC group.

CONCLUSIONS

These findings imply that LC produced increased neutralizing antibody responses than those with HC. During the Omicron pandemic, immunity after LC has still waned; therefore, a booster vaccine may be needed after 2-3 months from last infection. (ClinicalTrials.govnumber,NCT05484700)
CRISPR/Cas12a-mediated ultrasensitive and on-site monkeypox viral testing
Authors: Zhao Furong , Wang Pei , Wang Haoxuan , Liu Sirui , Sohail Muhammad , Zhang Xing , Li Bingzhi , Huang He
Published: October 2022

The unexpected transmission of monkeypox virus (MPXV) from Central and West Africa to previously non-endemic locations is triggering a global panic. The ultrasensitive, rapid, and specific detection of MPXV is crucial for controlling its spreading, while such technology has rarely been reported. Herein, we proposed an MPXV assay combining recombinase-aided amplification (RAA) and CRISPR/Cas12a for the first time. This assay targeted MPXVF3Lgene and yielded a low detection limit (LOD) of 101copies/μL. Deriving from the high specificity nature of RAA and CRISPR/Cas12a, through rational optimizations of probes and conditions, this assay showed high selectivity that could distinguish MPXV from other orthopox viruses and current high-profile viruses. To facilitate on-site screening of potential MPXV carriers, a kit integrating lateral flow strips was developed, enabling naked-eye MPXV detection with a LOD of 104copies/μL. Our RAA-Cas12a-MPXV assay was able to detect MPXV without the need for sophisticated operation and expensive equipment. We envision that this RAA-Cas12a-MPXV assay can be deployed in emerging viral outbreaks for on-site surveillance of MPXV.

For TOC only
A Concerted Mechanism Involving ACAT and SREBPs By which Oxysterols Deplete Accessible Cholesterol To Restrict Microbial Infection
Authors: Heisler David B. , Johnson Kristen A. , Ohlson Maikke B. , Ma Duo , Zhang Lishu , Tran Michelle , Corley Chase D. , Abrams Michael E. , McDonald Jeffrey G. , Schoggins John W. , Alto Neal M. , Radhakrishnan Arun
Published: October 2022

Most of the cholesterol in the plasma membranes (PMs) of animal cells is sequestered through interactions with phospholipids and transmembrane domains of proteins. However, as cholesterol concentration rises above the PM’s sequestration capacity, a new pool of cholesterol, called accessible cholesterol, emerges. The transport of accessible cholesterol between the PM and the endoplasmic reticulum (ER) is critical to maintain cholesterol homeostasis. This pathway has also been implicated in the suppression of both bacterial and viral pathogens by immunomodulatory oxysterols. Here, we describe a mechanism of depletion of accessible cholesterol from PMs by the oxysterol 25-hydroxycholesterol (25HC). We show that 25HC-mediated activation of acyl coenzyme A: cholesterol acyltransferase (ACAT) in the ER creates an imbalance in the equilibrium distribution of accessible cholesterol between the ER and PM. This imbalance triggers the rapid internalization of accessible cholesterol from the PM, which is sustained for long periods of time through 25HC-mediated suppression of SREBPs. In support of a physiological role for this mechanism, 25HC failed to suppress Zika virus and human coronavirus infection in ACAT-deficient cells, andListeria monocytogenesinfection in ACAT-deficient cells and mice. We propose that selective depletion of accessible PM cholesterol triggered by ACAT activation and sustained through SREBP suppression underpins the immunological activities of 25HC and a functionally related class of oxysterols.
Publicly Available Privacy-preserving Benchmarks for Polygenic Prediction
Authors: Witteveen Menno J. , Pedersen Emil M. , Meijsen Joeri , Andersen Michael Riis , Privé Florian , Speed Doug , Vilhjálmsson Bjarni J.
Published: October 2022

Recently, several new approaches for creating polygenic scores (PGS) have been developed and this trend shows no sign of abating. However, it has thus far been challenging to determine which approaches are superior, as different studies report seemingly conflicting benchmark results. This heterogeneity in benchmark results is in part due to different outcomes being used, but also due to differences in the genetic variants being used, data preprocessing, and other quality control steps. As a solution, a publicly available benchmark for polygenic prediction is presented here, which allows researchers to bothtrainandtestpolygenic prediction methods using only summary-level information, thus preserving privacy. Using simulations and real data, we show that model performance can be estimated with accuracy, using only linkage disequilibrium (LD) information and genome-wide association summary statistics for target outcomes. Finally, we make this PGS benchmark - consisting of 8 outcomes, including somatic and psychiatric disorders - publicly available for researchers to download on our PGS benchmark platform (http://www.pgsbenchmark.org). We believe this benchmark can help establish a clear and unbiased standard for future polygenic score methods to compare against.
Efficient and rapid fluorescent protein knock-in with universal donors in mammalian stem cells
Authors: Shi Yu , Kopparapu Nitya , Ohler Lauren , Dickinson Daniel J.
Published: October 2022

Fluorescent protein (FP) tagging is a foundational approach in cell biology because it allows observation of protein distribution, dynamics, and interaction with other proteins in living cells. However, the typical approach using overexpression of tagged proteins can perturb cell behavior and introduce localization artifacts. To preserve native expression, fluorescent proteins can be inserted directly into endogenous genes. This approach has been standard in yeast for decades, and more recently in invertebrate model organisms with the advent of CRISPR/Cas9. However, endogenous fluorescent protein tagging has not been widely used in mammalian cells due to inefficient homology-directed repair (HDR). Here, we describe a streamlined method for efficient and fast integration of FP tags into native loci via non-homologous end joining (NHEJ) in mouse embryonic stem cells. Our protocol minimizes cloning with universal donors, allows for N or C-terminal tagging of endogenous proteins, and requires less than 2 weeks from transfection to imaging, thereby improving the applicability of FP knock-in in mammalian cells.
Gαs slow conformational transition upon GTP binding and a novel Gαs regulator
Authors: Ahn Donghoon , Provasi Davide , Duc Nguyen Minh , Xu Jun , Salas-Estrada Leslie , Spasic Aleksandar , Yun Min Woo , Kang Juyeong , Gim Dongmin , Lee Jaecheol , Du Yang , Filizola Marta , Chung Ka Young
Published: October 2022

G proteins are major signaling partners for G protein-coupled receptors (GPCRs). Although stepwise structural changes during GPCR–G protein complex formation and guanosine diphosphate (GDP) release have been reported, no information is available with regard to guanosine triphosphate (GTP) binding. Here, we used a novel Bayesian integrative modeling framework that combines data from hydrogen-deuterium exchange mass spectrometry, tryptophan-induced fluorescence quenching, and metadynamics simulations to derive a kinetic model and atomic-level characterization of stepwise conformational changes incurred by the β2-adrenergic receptor (β2AR)-Gs complex after GDP release and GTP binding. Our data suggest rapid GTP binding and GTP-induced dissociation of Gαs from β2AR and Gβγ, as opposed to a slow closing of the Gαs α-helical domain (AHD). Yeast-two-hybrid screening using Gαs AHD as bait identified melanoma-associated antigen D2 (MAGE D2) as a novel AHD-binding protein, which was also shown to accelerate the GTP-induced closing of the Gαs AHD.
Novel genetic traits inXanthomonasunveiled by the complete genome sequencing of three clade-1 xanthomonads
Authors: Peduzzi Chloé , Sagia Angeliki , Burokienė Daiva , Nagy Ildikó Katalin , Saux Marion Fischer-Le , Portier Perrine , Dereeper Alexis , Cunnac Sébastien , Roman-Reyna Veronica , Jacobs Jonathan M. , Bragard Claude , Koebnik Ralf
Published: October 2022

Evolutionary early-branching xanthomonads, also referred to as clade-1 xanthomonads, include major plant pathogens, most of which colonize monocotyledonous plants. Seven species have been validly described, among them the two sugarcane pathogensXanthomonas albilineansandXanthomonas sacchari, andXanthomonas translucens, which infects small grain cereals, diverse grasses, but also asparagus and pistachio trees. Single-gene sequencing and genomic approaches indicated that this clade likely contains more, yet undescribed species. In this study, we sequenced representative strains of three novel species using long-read sequencing technology.Xanthomonassp. pv.phormiicolastrain CFBP 8444 causes bacterial streak on New Zealand flax, another monocotyledonous plant.Xanthomonassp. strain CFBP 8443 has been isolated from common bean andXanthomonassp. strain CFBP 8445 originated from banana. Complete assemblies of the chromosomes confirmed their unique taxonomic position within clade 1 ofXanthomonas. Genome mining revealed novel genetic traits, hitherto undescribed in other members of theXanthomonasgenus. In strain CFBP 8444, we identified genes related to the synthesis of coronatine-like compounds, a phytotoxin produced by several pseudomonads, which raises interesting questions about the evolution and pathogenicity of this pathogen. In addition, strain CFBP 8444 was found to encode a second, atypical flagellar gene cluster in addition to the canonical flagellar gene cluster. Overall, this research represents an important step toward better understanding the evolutionary history and biology of early-branching xanthomonads.
Variation in the rate lateral gene transfers accumulate in a grass lineage
Authors: Raimondeau Pauline , Bianconi Matheus E. , Pereira Lara , Parisod Christian , Christin Pascal-Antoine , Dunning Luke T.
Published: October 2022

Lateral gene transfer (LGT) has been reported in multiple eukaryotes. This process seems particularly widespread in the grass family, although we know very little about the underlying dynamics and how it impacts gene content variation within a species.Alloteropsis semialatais a tropical grass, and multiple LGT were detected in a reference genome assembled from an Australian individual. As part of this study we assemble three additionalde novogenomes forA. semialataand one for its sister speciesAlloteropsis angusta. In total we detect 168 LGT across the five reference genomes. Using whole-genome resequencing data for a further 40 individuals we establish the distribution of these transfers and map their origin along the species phylogeny. This shows that many LGTs were acquired relatively recently, with numerous secondary losses. Exponential decay models indicate that the rate of LGT acquisitions varied significantly among lineages [6-28 per Ma], with a high rate of subsequent LGT losses [11-24% per Ma] that largely exceeds that of native loci [0.02-0.8% per Ma]. This high turnover creates large intraspecific structural variants, with a preponderance of LGT occurring as accessory genes in theAlloteropsispangenome. The acquired genes represent unparalleled genetic novelties, having independently evolved for tens of millions of years before they were transferred. Ultimately, the rapid LGT turnover generates standing variation that can fuel local adaptation.
Modeling of possible quadruplexes and i-motifs formed during DNA contacts: strategy, classification, most probable shapes, origami based on quadruplexes
Authors: Tsvetkov Vladimir B.
Published: October 2022

A strategy for creating 3D models of non-canonical forms of DNA and RNA is proposed in this research. Through this strategy, models of all possible forms of non-canonical structures created by contacts of single-stranded DNA with sequence (G3T)nG3and/or duplexes with (G3T)nG3and (C3A)nC3fragments were built and tested by MD. In particular, models of stacks formed from right and left twisted quadruplexes; the structure resembling the Holliday structure, with the hole, on the border of which the quadruplex (G4) and the i-motif (IM) were located opposite each other; layers formed from G4s grids were constructed. The most probable of these non-canonical forms arising from contacts of duplexes with (G3T)nG3for n=1,3,5 were determined by estimating the contributions to the free energy.