bluuebunny/crossref_metadata_2025 huggingface dataset:
Durability analysis of the highly effective BNT162b2 vaccine against COVID-19
Authors: Puranik Arjun , Lenehan Patrick J , O'Horo John C , Pawlowski Colin , Niesen Michiel J M , Virk Abinash , Swift Melanie D , Kremers Walter , Venkatakrishnan A J , Gordon Joel E , Geyer Holly L , Speicher Leigh Lewis , Soundararajan Venky , Badley Andrew D
Published: June 2022

COVID-19 vaccines are effective, but breakthrough infections have been increasingly reported. We conducted a test-negative case-control study to assess the durability of protection after full vaccination with BNT162b2 against polymerase chain reaction (PCR)-confirmed symptomatic SARS-CoV-2 infection, in a national medical practice from January 2021 through January 2022. We fit conditional logistic regression (CLR) models stratified on residential county and calendar time of testing to assess the association between time elapsed since vaccination and the odds of symptomatic infection or non-COVID-19 hospitalization (negative control), adjusted for several covariates. There were 5,985 symptomatic individuals with a positive test after full vaccination with BNT162b2 (cases) and 32,728 negative tests contributed by 27,753 symptomatic individuals after full vaccination (controls). The adjusted odds of symptomatic infection were higher 250 days after full vaccination versus at the date of full vaccination (Odds Ratio [OR]: 3.62, 95% CI: 2.52 to 5.20). The odds of infection were still lower 285 days after the first BNT162b2 dose as compared to 4 days after the first dose (OR: 0.50, 95% CI: 0.37 to 0.67), when immune protection approximates the unvaccinated status. Low rates of COVID-19 associated hospitalization or death in this cohort precluded analyses of these severe outcomes. The odds of non-COVID-19 associated hospitalization (negative control) decreased with time since vaccination, suggesting a possible underestimation of waning protection by this approach due to confounding factors. In summary, BNT162b2 strongly protected against symptomatic SARS-CoV-2 infection for at least 8 months after full vaccination, but the degree of protection waned significantly over this period.
Development of social feedback processing and responses in childhood: an fMRI test-replication design in two age cohorts
Authors: Dobbelaar Simone , Achterberg Michelle , van Drunen Lina , van Duijvenvoorde Anna c.k , van IJzendoorn Marinus H , Crone Eveline A
Published: June 2022

This study investigated behavioral and neural correlates underlying social feedback processing and subsequent aggressive behaviors in childhood in two age cohorts (test sample: n = 509/n = 385 and replication sample: n = 354/n = 195, 7–9 years old). Using a previously validated Social Network Aggression Task, we showed that negative social feedback resulted in most behavioral aggression, followed by less aggression after neutral and least aggression after positive feedback. Receiving positive and negative social feedback was associated with increased activity in the insula, medial prefrontal cortex and ventrolateral prefrontal cortex. Responding to feedback was associated with additional activation in the dorsolateral prefrontal cortex (DLPFC) following positive feedback. This DLPFC activation correlated negatively with aggression. Furthermore, age analyses showed that older children showed larger reductions in aggression following positive feedback and more neural activation in the DLPFC when responding to positive feedback compared to younger children. To assess the robustness of our results, we examined these processes in two independent behavioral/functional magnetic resonance imaging samples using equivalence testing, thereby contributing to replicable reports. Together, these findings demonstrate an important role of social saliency and regulatory processes where regulation of aggression rapidly develops between the ages of 7 and 9 years.
A need for diet assessment technology for South Asians living in the USA
Authors: Hussain Bridget Murphy , Talegawkar Sameera A , Shivakoti Rupak , Parekh Niyati
Published: June 2022

South Asians are among the fastest growing ethnic group in the USA yet remain understudied in epidemiologic studies. Due to their unique disease profile, identifying risk moderators and mitigators, such as dietary patterns and food intake, will help to determine the diet–disease relationship that is specific to this largely immigrant population group in the USA. The aim of this commentary is to highlight the dietary traditions and acculturated practices experienced by South Asians in the USA with a call for a diet assessment instrument that adequately captures their dietary diversity. Specifically, we call for (i) the inclusion of traditional food items, such as herbs and spices, that individualize diet assessment for participants; and (ii) leveraging technology that will enhance the experience of diet assessment for both researchers and participants, tailoring the collection of habitual dietary intake in this diverse population group.
Identification and prioritization of key health hazards to workers in roadway construction
Authors: Mo Shicong , Wang Yuhong , Xiong Feng
Published: June 2022

Although various rating systems have been developed to promote sustainable development in roadway construction, sustainability evaluation from the perspective of safeguarding workers’ health is currently lacking. Three approaches were used in the study to identify and prioritize key health hazards to workers in roadway construction, including bibliometric analysis, questionnaire survey and analytic hierarchy process (AHP). Bibliometric analysis indicates that submicron particles and polycyclic aromatic compounds are the primary concerns of researchers, and ergonomics also attracts some attention. A questionnaire survey was conducted among construction workers in China. The results suggest that the most frequently encountered occupational disorders by roadway construction workers are musculoskeletal disorders, heat stroke, respiratory health issues and hearing loss, and the most commonly encountered hazards are noise, dust, asphalt fumes, heat stress and some adverse working conditions. Perceptions on associations between the health hazards and disorders were obtained. Although there are some discrepancies between the AHP scores provided by two groups of professionals in China, the commonly agreed top occupational hazards include dust, asphalt fumes, noise, high-/low-temperature stresses and chronic injuries. The findings may be incorporated into rating systems for roadway construction to encourage the industry to adopt better practices for the well-being of workers.
Coronaviruses in wild animals sampled in and around Wuhan at the beginning of COVID-19 emergence
Authors: Wang Wen , Tian Jun-Hua , Chen Xiao , Hu Rui-Xue , Lin Xian-Dan , Pei Yuan-Yuan , Lv Jia-Xin , Zheng Jiao-Jiao , Dai Fa-Hui , Song Zhi-Gang , Chen Yan-Mei , Zhang Yong-Zhen
Published: June 2022

Over the last several decades, no emerging virus has had a profound impact on the world as the SARS-CoV-2 that emerged at the end of 2019 has done. To know where severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originated from and how it jumped into human population, we immediately started a surveillance investigation in wild mammals in and around Wuhan when we determined the agent. Herein, coronaviruses were screened in the lung, liver, and intestinal tissue samples from fifteen raccoon dogs, seven Siberian weasels, three hog badgers, and three Reeves’s muntjacs collected in Wuhan and 334 bats collected around Wuhan. Consequently, eight alphacoronaviruses were identified in raccoon dogs, while nine betacoronaviruses were found in bats. Notably, the newly discovered alphacoronaviruses shared a high whole-genome sequence similarity (97.9 per cent) with the canine coronavirus (CCoV) strain 2020/7 sampled from domestic dog in the UK. Some betacoronaviruses identified here were closely related to previously known bat SARS-CoV-related viruses sampled from Hubei province and its neighbors, while the remaining betacoronaviruses exhibited a close evolutionary relationship with SARS-CoV-related bat viruses in the RdRp gene tree and clustered together with SARS-CoV-2-related bat coronaviruses in the M, N and S gene trees, but with relatively low similarity. Additionally, these newly discovered betacoronaviruses seem unlikely to bind angiotensin-converting enzyme 2 because of the deletions in the two key regions of their receptor-binding motifs. Finally, we did not find SARS-CoV-2 or its progenitor virus in these animal samples. Due to the high circulation of CCoVs in raccoon dogs in Wuhan, more scientific efforts are warranted to better understand their diversity and evolution in China and the possibility of a potential human agent.
Adapting an Interdisciplinary Learning Health System Framework for Academic Health Centers: A Scoping Review
Authors: Anderson Jami L. , Mugavero Michael J. , Ivankova Nataliya V. , Reamey Rebecca A. , Varley Allyson L. , Samuel Shekwonya E. , Cherrington Andrea L.
Published: June 2022

Purpose

Learning health systems (LHSs), defined as a systematic process for aligning science, informatics, and clinical practice to integrate providers, researchers, and patients as active participants in an evidence-based care continuum, can provide an ideal environment for academic health centers to rapidly adopt evidence-based guidelines and translate research into practice. However, few LHS frameworks are specifically adapted for academic health centers. The authors wanted to identify the definitions, components, and other features of LHSs to develop an interdisciplinary LHS framework for use within academic health centers.

Method

The authors conducted a scoping review of the literature to identify definitions, components, and other features of LHSs that are useful to academic health centers. In January 2021, they searched PubMed, Academic Search Premier, and Scopus databases and identified English-language, peer-reviewed articles pertaining to LHS, LHS frameworks, organization, components, and models. Since the phraselearning health systemis relatively new terminology, they conducted a supplemental review with alternative phrases, includingembedded researchandcoordinatedorcollaborative research network. They used the Knowledge to Action (KTA) Framework to integrate the generation and flow of research into practice.

Results

The primary review retrieved 719 articles and the supplemental review retrieved 209; of these, 49 articles were retained to synthesize common definitions, components, and other features of LHS frameworks. Seven structural components of LHSs were identified: organization and collaborations, performance, ethics and security, scientific approaches, data, information technology, and patient outcomes. An adapted interdisciplinary LHS framework was developed that incorporated research and learning engines derived from the KTA and adaptations of common components and other features within the reviewed articles to fit the interests of providers, researchers, and patients within academic health centers.

Conclusions

The adapted LHS framework can be used as a dynamic foundation for development and organization of interdisciplinary LHSs within academic health centers.
Grit, Gratitude, Grace, and Guidance: Moving Academic Medicine From Crisis to Transformation
Authors: Belfi Lily M. , Weissman Eric , Haramati Aviad
Published: June 2022

Since the beginning of the COVID-19 crisis within the United States, faculty in academic medicine have experienced serious workplace and personal challenges while also exploring unique solutions and innovations in response to these challenges. Despite the global pandemic, social inequality and unrest, and uncertainty about the future, 3 hopeful themes that bind faculty together have emerged: grit, gratitude, and grace. This commentary describes how these qualities are in fact a culmination of ongoing work within academic medicine. While there is still a long way to go, this work is paving a path forward that is leading faculty to have more control over their professional lives. Indeed, these faculty efforts can be enhanced through shared governance, in which faculty participate more fully in the decision making at their institutions. To create thoughtful and enduring solutions, institutional leadership need to collaborate with faculty and provide guidance focused on improving well-being among faculty. This commentary is a call to action that describes how working together through shared purpose and engagement can harness the power of crisis as a catalyst for change and transformation that leads to the betterment of not just faculty, but academic medicine overall.
A comparison of pain, fatigue, and function between post–COVID-19 condition, fibromyalgia, and chronic fatigue syndrome: a survey study
Authors: Haider Saman , Janowski Adam J. , Lesnak Joseph B. , Hayashi Kazuhiro , Dailey Dana L. , Chimenti Ruth , Frey-Law Laura A. , Sluka Kathleen A. , Berardi Giovanni
Published: June 2022

A growing number of individuals report prolonged symptoms following acute Coronavirus-19 (COVID-19) infection, known as post–COVID-19 condition (post-COVID-19). While studies have emerged investigating the symptom sequelae of post-COVID-19, there has been limited investigation into the characterization of pain, fatigue, and function in these individuals, despite initial reports of a clinical phenotype similar to fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME). This study aimed to characterize multiple symptom domains in individuals reporting post–COVID-19 and compare its clinical phenotype with those with FMS and CFS. A total of 707 individuals with a single or comorbid diagnosis of post–COVID-19, FMS, and/or CFS completed multiple surveys assessing self-reported pain, fatigue, physical and cognitive function, catastrophizing, kinesiophobia, anxiety, depression, dyspnea, and sleep quality. In all 3 diagnoses, elevated pain, fatigue, anxiety, depression, catastrophizing, and kinesiophobia were reported. Physical and cognitive function were similarly impacted among individuals with post-COVID-19, FMS, and CFS; however, individuals with post-COVID-19 reported lower pain and fatigue than FMS and CFS. The comorbid diagnosis of post-COVID-19 with FMS and/or CFS further exacerbated pain, fatigue, and psychological domains when compared with post-COVID-19 alone. In summary, individuals with post-COVID-19 report a symptom phenotype similar to FMS and CFS, negatively impacting cognitive and physical function, but with less severe pain and fatigue overall. These findings may help direct future investigations of the benefit of a biopsychosocial approach to the clinical management of post-COVID-19.
Mining database and verification of PIK3CB as a marker predicting prognosis and immune infiltration in renal clear cell carcinoma
Authors: Ye Jianzhong , Zeng Tao
Published: June 2022

Background:

Kidney renal clear cell carcinoma (KIRC) was the most prevalent malignancy of urinary system. Phosphatidylinositol 3-kinase pathway exerted a vital function in tumor proliferation, invasion, and survival by integrating extracellular growth signals.

Methods:

The expression and clinical significance of PIK3CB in KIRC was explored using bioinformatics analysis. And qRT-PCR was performed to verify our results.

Results:

PIK3CB was downregulated at mRNA and protein level in KIRC. KIRC patients with low PIK3CB expression indicated a worse overall survival, progression free survival, and disease-free survival. A predictive nomogram was constructed and demonstrated that the predicted calibration plots for 1-year, 3-year, and 5-year OS probabilities showed good agreement compared with the actual OS of KIRC patients. Validation research demonstrated a downregulation of PIK3CB in KIRC tissues and a poor overall survival in KIRC patients with low PIK3CB expression. Furthermore, Cox regression analysis revealed that PIK3CB expression was an independent prognostic factor for KIRC. PIK3CB expression showed positive correlation with the abundance of immune cells. Moreover, enrichment analysis revealed that PIK3CB and associated genes were mainly associated with RNA splicing and JAK-STAT signaling pathway.

Conclusion:

Our study suggested that PIK3CB was a potential biomarker for prognosis and correlated with immune infiltrates in KIRC.
Unusual manifestations of adrenal insufficiency
Authors: Hsu Chia-Chen , Lin Hong-Da , Huang Chung-Yen , Chiang Yi-Lun
Published: June 2022

Rationale:

Pituitary apoplexy occurs in about 8% of those with nonfunctioning pituitary adenoma. Subsequent hormone deficiency, especially corticotropic deficiency, is the most common finding. We describe the unusual manifestations of adrenal insufficiency that are usually overlooked in such cases, with the aim of raising awareness of this disease.

Patient concerns:

A 53-year-old male with a history of hyponatremia came to our hospital with intermittent fever and generalized pruritic skin rash. He also reported general weakness, abdominal pain, poor appetite, and severe retroorbital headache.

Diagnoses:

Laboratory data revealed hypereosinophilia, hypotonic hyponatremia, and hypopituitarism, including secondary adrenal insufficiency. Sellar magnetic resonance imaging revealed a pituitary macroadenoma, 2 cm in height, with mild displacement of the optic chiasm. Pathologic report and immunohistochemical stains of surgical specimen showed pituitary gonadotropic adenoma with apoplexy.

Interventions:

Transsphenoidal removal of the pituitary adenoma was performed. The patient received intravenous hydrocortisone then oral form cortisone acetate regularly.

Outcomes:

His symptoms and laboratory data recovered after the operation and medical treatment.

Lessons:

This case highlights that eosinophilia, pruritic skin rash and fever can be manifestations of adrenal insufficiency, and that they may initially be regarded as cellulitis.
Percutaneous vertebroplasty in osteoporotic vertebral compression fracture with huge spinal epidural hematoma
Authors: Wang Huafeng , Lin Fengfei , Liang Guiqing , Lin Yuhan
Published: June 2022

Rationale:

Osteoporotic vertebral compression fracture (OVCF) accompanying huge spinal epidural hematoma (SEH) is fairly rare. The aim of this report is to investigate the management strategies and treatment outcomes of OVCF accompanying SEH.

Patient concerns:

An 89-year-old female patient was admitted to hospital because of severe back pain and numbness of both lower limbs after a slight fall. The magnetic resonance imaging examination of the patient showed a fresh compression fracture at L2 accompanying a large dorsal SEH which extended from the T12 to L3 and deformed the spinal cord.

Diagnosis:

The patient was diagnosed with OVCF accompanying SEH.

Interventions:

Given mild neurologic deficits, the hematoma was not treated, and the patient underwent percutaneous vertebroplasty (PVP) only.

Outcomes:

After the procedure, immediate pain relief was achieved and the numbness of both lower limbs disappeared 3 days later. Three months after the procedure, the follow-up magnetic resonance imaging revealed a complete resolution of the hematoma.

Lessons:

OVCF accompanying SEH is fairly rare, and the exact pathophysiological mechanisms are still not clear. In selected patients without or with only slight neurologic symptoms, it is reasonable to perform PVP alone in OVCF accompanying SEH. Moreover, intravertebral stability after PVP might have played a role in spontaneous resolution of SEH.
Pleiotropic effects on proliferation and mineralization of primary human adipose tissue-derived stromal cells induced by simvastatin
Authors: Sabandal Martin Mariano Isabelo , Schäfer Edgar , Petsching Simon , Jung Susanne , Kleinheinz Johannes , Sielker Sonja
Published: June 2022

The circulating low-density lipoprotein concentration in blood can be reduced by the administration of statins. Frequently simvastatin (SV) is prescribed. Due to the reported pleiotropic effects of SV the aim of this study was to evaluate mineralization effects on human adipose tissue-derived stromal cells upon administration of SV. After informed consent human adipose tissue-derived stromal cells were obtained from tissue surplus of regular treatments of 14 individuals. According to established protocols after adding various SV concentrations (0.01 µM, 0.1 µM, 1.0 µM, 2.0 µM), alkaline phosphate (osteoblastic marker), mineralization capability and viability were determined at day 18, 21 and 28. The Kruskal–Wallis test was performed for statistical analysis. After adding SV a dose-dependent significant decreased viability and levels of alkaline phosphatase (
p
< 0.01) and a significantly increased mineralization (
p
< 0.01) of the primary cultures was recognized during the late mineralization stage. Mineralization of the human adipose tissue-derived stromal cells was induced by SV, possibly originated from alternative pathways than the alkaline phosphatase pathway. Further investigations should be performed regarding switching into the osteoblastic differentiation and as a possible source of cells that can be used as the basis for a potential bone graft substitute, which may allow an extension of the field of application.
Turning-ascending flight of a
Hipposideros pratti
bat
Authors: Rahman Aevelina , Windes Peter , Tafti Danesh
Published: June 2022

Bats exhibit a high degree of agility and provide an excellent model system for bioinspired flight. The current study investigates an ascending right turn of a
Hipposideros pratti
bat and elucidates on the kinematic features and aerodynamic mechanisms used to effectuate the manoeuvre. The wing kinematics captured by a three-dimensional motion capture system is used as the boundary condition for the aerodynamic simulations featuring immersed boundary method. Results indicate that the bat uses roll and yaw rotations of the body to different extents synergistically to generate the centripetal force to initiate and sustain the turn. The turning moments are generated by drawing the wing inside the turn closer to the body, by introducing phase lags in force generation between the wings and redirecting force production to the outer part of the wing outside of the turn. Deceleration in flight speed, an increase in flapping frequency, shortening of the upstroke and thrust generation at the end of the upstroke were observed during the ascending manoeuvre. The bat consumes about 0.67 W power to execute the turning-ascending manoeuvre, which is approximately two times the power consumed by similar bats during level flight. Upon comparison with a similar manoeuvre by a
Hipposideros armiger
bat (Windes
et al
. 2020
Bioinspir. Biomim
.
16
, abb78d. (
doi:10.1088/1748-3190/abb78d
)), some commonalities, as well as differences, were observed in the detailed wing kinematics and aerodynamics.
Mesoporous silica nanocarriers as drug delivery systems for anti-tubercular agents: a review
Authors: Tella Josephine Oluwagbemisola , Adekoya Joseph Adeyemi , Ajanaku Kolawole Oluseyi
Published: June 2022

The treatment and management of tuberculosis using conventional drug delivery systems remain challenging due to the setbacks involved. The lengthy and costly treatment regime and patients' non-compliance have led to drug-resistant tuberculosis, which is more difficult to treat. Also, anti-tubercular drugs currently used are poor water-soluble drugs with low bioavailability and poor therapeutic efficiency except at higher doses which causes drug-related toxicity. Novel drug delivery carrier systems such as mesoporous silica nanoparticles (MSNs) have been identified as nanomedicines capable of addressing the challenges mentioned due to their biocompatibility. The review discusses the sol–gel synthesis and chemistry of MSNs as porous drug nanocarriers, surface functionalization techniques and the influence of their physico-chemical properties on drug solubility, loading and release kinetics. It outlines the physico-chemical characteristics of MSNs encapsulated with anti-tubercular drugs.
Temporal dynamics and fitness consequences of coalition formation in male primates
Authors: Neumann Christof , Kulik Lars , Agil Muhammad , Engelhardt Antje , Widdig Anja
Published: June 2022

Coalition formation is one of the most striking forms of cooperation found in animals. Yet, there is substantial variation between taxa regarding the mechanisms by which coalitions can result in fitness consequences. Here, we investigate the influence of coalitions on dominance rank trajectories and subsequently on reproductive success in wild male crested macaques (
Macaca nigra
) at Tangkoko Nature Reserve (Sulawesi, Indonesia). We observed 128 coalition events involving 28 males and tested how a variety of coalition properties and factors related to the social environment influenced future male rank. We further used genetic paternity analysis of 19 infants conceived during the study to assess male reproductive success. Our results show that males participating in coalitions achieved higher-than-expected future ranks, while coalition targets had lower-than-expected future ranks. Additionally, all-up coalitions had stronger effects on rank than all-down and bridging coalitions, and these were modulated by the relative strength of coalition partners versus targets. Finally, higher ranking males were more likely to sire infants than lower ranking males. These results provide important insights regarding the mechanisms underlying coalition formation and support the idea that one major path by which coalitions can affect fitness is through influencing male dominance trajectories.
The correlated evolution of foraging mode and reproductive effort in lizards
Authors: Padilla Perez Dylan J. , DeNardo Dale F. , Angilletta Jr Michael J.
Published: June 2022

Life-history theory suggests that the optimal reproductive effort of an organism is affected by factors such as energy acquisition and predation risk. The observation that some organisms actively search for their prey and others ambush them creates the expectation of different energy needs and predation risk associated with each foraging behaviour, the so-called ‘foraging-mode paradigm’. Although this paradigm has been around for decades, the empirical evidence consists of conflicting results derived from competing models based on different mechanisms. For instance, models within the foraging-mode paradigm suggest that widely foraging females have evolved low reproductive effort, because a heavy reproductive load decreases their ability to escape from predators. By contrast, a long-standing prediction of evolutionary theory indicates that organisms subject to high extrinsic mortality, should invest more in reproduction. Here, we present the first partial evidence that widely foraging species have evolved greater reproductive effort than have sit-and-wait species, which we attribute to a larger body size and greater mortality among mobile foragers. According to our findings, we propose a theoretical model that could explain the observed pattern in lizards, suggesting ways for evolutionary ecologists to test mechanistic hypotheses at the intraspecific level.
Local accessory gene sharing among Egyptian Campylobacter potentially promotes the spread of antimicrobial resistance
Authors: Mouftah Shaimaa F. , Pascoe Ben , Calland Jessica K. , Mourkas Evangelos , Tonkin Naomi , Lefevre Charlotte , Deuker Danielle , Smith Sunny , Wickenden Harry , Hitchings Matthew D. , Sheppard Samuel K. , Elhadidy Mohamed
Published: June 2022

Campylobacter

is the most common cause of bacterial gastroenteritis worldwide, and diarrhoeal disease is a major cause of child morbidity, growth faltering and mortality in low- and middle-income countries. Despite evidence of high incidence and differences in disease epidemiology, there is limited genomic data from studies in developing countries. In this study, we aimed to quantify the extent of gene sharing in local and global populations. We characterized the genetic diversity and accessory-genome content of a collection of

Campylobacter

isolates from the Cairo metropolitan area, Egypt. In total, 112

Campylobacter

isolates were collected from broiler carcasses (n=31), milk and dairy products (n=24), and patients suffering from gastroenteritis (n=57). Among the most common sequence types (STs), we identified the globally disseminated host generalist ST-21 clonal complex (CC21) and the poultry specialists CC206, CC464 and CC48. Notably, CC45 and the cattle-specialist CC42 were under-represented, with a total absence of CC61. Core- and accessory-genome sharing was compared among isolates from Egypt and a comparable collection from the UK (Oxford). Lineage-specific accessory-genome sharing was significantly higher among isolates from the same country, particularly CC21, which demonstrated greater local geographical clustering. In contrast, no geographical clustering was noted in either the core or accessory genome of CC828, suggesting a highly admixed population. A greater proportion of

Campylobacter coli

isolates were multidrug resistant compared to

Campylobacter jejuni

. Our results suggest that there is more horizontal transfer of accessory genes between strains in Egypt. This has strong implications for controlling the spread of antimicrobial resistance among this important pathogen.
Income and Race-Ethnicity Disparities in Medical Care Utilization and Expenditures in the United States, 2017-2019
Authors: Wetzler Harry , Cobb Herbert
Published: June 2022

Background

The COVID-19 pandemic has focused attention on race and income disparities in SARS-CoV-2 mortality and morbidity. Much less attention has been paid to other socioeconomic factors including income.

Objective

The goal of this study was to compare disparities in medical care utilization and related expenditures associated with income to those associated with race and ethnicity in the US for those aged 0 to 64 for four categories of medical services: hospital, emergency room, ambulatory care, and prescription medications.

Methods

We used Medical Expenditure Panel Survey data for years 2017 through 2019. For each of the four medical services, there were three measures. First was the percentage of those aged 0-64 with or without utilization and expenditures. Due to statistical issues related to zero values for utilization and expenditures, the second and third measures were average utilization and expenditures only for those with both utilization and expenditures. Disparities by income and race-ethnicity were measured by calculating the percent difference between the group with the lowest utilization or expenditures and the group with the highest utilization or expenditures.

Results

For 9 of the 12 separate differences the income differences exceed the corresponding race-ethnicity difference and the income differences are generally much greater in magnitude. Within the income comparisons, those on Medicaid had the greatest utilization in 7 of the 8 comparisons. The High Income group had greatest expenditures for 3 of the 4 medical services. Non-Hispanic Whites had the greatest utilization and expenditures for 9 of the 12 measures and Hispanics had the least utilization and expenditures for 9 of the 12 measures.

Conclusions

These results indicate that income inequalities are more strongly associated with medical care utilization and expenditures than race-ethnicity among those aged 0-64. Although more research should focus on income related health disparities in the United States, it is time to recognize that sound health policy must include reducing socioeconomic inequalities, especially those related to income.
Recessive and sex-dependent genetic effects in primary hypertension
Authors: Zucker Roei , Linial Michal
Published: June 2022

Background

Essential hypertension is a polygenic disease that affects almost half of the adult population in the USA. It is a major risk factor for renal, cerebrovascular, and cardiovascular diseases. Previous studies used UK-Biobank (UKB) GWAS results for hypertension to create a polygenic risk score (PRS), with the top and bottom 5% of the PRS translating to a 4-fold difference in the estimated risk. The heritability of hypertension is estimated to be high (30–60%), yet the underlying mechanisms and the associated genes are largely unknown.

Methods

In this study, we used a gene-based method, the proteome-wide association study (PWAS), to detect associations mediated by the effects of variants on protein function. PWAS was applied to individuals of European ancestry from the UKB, with 74,090 cases of clinical diagnosis of essential (primary) hypertension (ICD-10, I10) and 200,734 controls. PWAS aggregates the signal from all variants affecting each coding gene and provides scores for dominant, recessive, and hybrid genetic heritability.

Results

PWAS identified 70 statistically significant associated genes (FDR-q-value <0.05) and 127 genes with a weaker threshold (FDR-q-value <0.1). The overlap with GWAS summary statistics (total 1,362 genes) is only partial, with 23 and 62 genes identified exclusively by PWAS from a total of 70 and 127 genes, respectively), among them 18% were assigned recessive inheritance. Furthermore, PWAS analysis, separately performed on females and males from UKB genotyping imputed data, revealed sex-dependent genetics. There are 22 genes unique in females, with only 2 in males. We identified 6 female-specific genes that were not identified by PWAS for the entire group (70 genes). Only one associated gene (SH2B3) is shared between the sexes. Many of the female-significant genes from PWAS are enriched in cellular immunity functions.

Conclusions

We conclude that hypertension displays sex-dependent genetics with an overlooked recessive inheritance, postulating that the underlying mechanism is substantially different for males and females. Studying hypertension by a gene-based association method improves interpretability and clinical utility.
Pregnancy during COVID-19: social contact patterns and vaccine coverage of pregnant women from CoMix in 19 European countries
Authors: Wong Kerry LM , Gimma Amy , Paixao Enny S ,   CoMix Europe Working Group, Faes Christel , Beutels Philippe , Hens Niel , Jarvis Christopher I , Edmunds W. John
Published: June 2022

Background

Evidence and advice for pregnant women evolved during the COVID-19 pandemic. We studied social contact behaviour and vaccine uptake in pregnant women between March 2020 and September 2021 in 19 European countries.

Methods

In each country, repeated online survey data were collected from a panel of nationally-representative participants. We calculated the mean adjusted contacts reported with an individual-level generalized additive mixed model, modelled using the negative binomial distribution and a log link function. Mean proportion of people in isolation or quarantine, and vaccination coverage by pregnancy status and gender were calculated using a clustered bootstrap.

Findings

We recorded 4,129 observations from 1,041 pregnant women, and 115,359 observations from 29,860 non-pregnant individuals aged 18-49. Pregnant women made slightly fewer contacts (3.6, 95%CI=3.5-3.7) than non-pregnant women (4.0, 95%CI=3.9-4.0), driven by fewer work contacts but marginally more contacts in non-essential social settings. Approximately 15-20% pregnant and 5% of non-pregnant individuals reported to be in isolation and quarantine for large parts of the study period.

COVID-19 vaccine coverage was higher in pregnant women than in non-pregnant women between January and April 2021. Since May 2021, vaccination in non-pregnant women began to increase and surpassed that in pregnant women.

Interpretation

Social contacts and vaccine uptake protect pregnant women and their newborn babies. Recognition of maternal social support need, and efforts to promote the safety and effectiveness of the COVID-19 vaccines during pregnancy are high priorities in this vulnerable group.
Of Problems and Opportunities – How to Treat and How to Not Treat Crystallographic Fragment-Screening Data
Authors: Weiss Manfred S. , Wollenhaupt Jan , Correy Galen J. , Fraser James S. , Heine Andreas , Klebe Gerhard , Krojer Tobias , Thunnissen Marjolein , Pearce Nicholas M.
Published: June 2022

In their recent commentary in Protein Science, Jaskolski et al. analyze three randomly picked diffraction data sets from fragment-screening group depositions from the PDB and, based on that, claim that such data are principally problematic. We demonstrate here that if such data are treated properly, none of the proclaimed criticisms persist.
The complexity of keratocyte migration in salmon explant cultures: initial results and future prospects
Authors: Opstad Ida S. , Wolfson Deanna L. , Ahluwalia Balpreet S. , Agarwal Krishna , Seternes Tore , Dalmo Roy A.
Published: June 2022

Intact skin is of uttermost importance for fish welfare. The fish skin provides an environmental barrier and protects against invading pathogens. However, both pathogens and physical insults cause skin wounds that are of major concern in modern fish farming. The behavior and interactions between keratocyte cells and sheets of cells are not well understood. The collective migration of keratocytes (skin epithelial cells) is of central importance for wound healing in fish. In this study, we aimed to elucidate the complex wound healing process in fish skin by studying in vitro cultures of these highly motile cells. Using explant cultures from farmed Atlantic salmon (Salmo salar) and differential interference contrast microscopy (DIC), we have captured the dynamics of sheets of cells from harvested fish scales and of individual cells interacting in the cell sheet vicinity. In addition to direct contact, the cells were observed to interact through long membrane tubes, turn, rotate, merge, and/or detach. Additionally, stationary cells and cells moving on top of the cell sheets were observed. Cell sheets approaching one another from different scales did not merge but dispersed.
Large errors increase the generalization of locomotor adaptation depending on the error direction
Authors: de Kam Digna , Staring Wouter , Mariscal Dulce M. , Torres-Oviedo Gelsy
Published: June 2022

Generalization in motor adaptation involves the transfer of movements beyond the adaptation context. We investigated the effect of size (large vs. small) and direction (unidirectional vs. bidirectional) of performance errors during adaptation on the generalization of walking patterns from a split-belt treadmill (training context) to overground (testing context). We hypothesized that unusual errors (i.e., large unidirectional or bidirectional errors) would serve as contextual cues limiting generalization. The size of unidirectional errors was modulated either implicitly (i.e., gradual vs. semi-abrupt split-belt perturbations) or explicitly (i.e., through instructed visual feedback). Bidirectional errors were induced by a sudden removal of the split-perturbation after a long adaptation period, resulting in errors in the opposite direction to those at the start of the adaptation period. Our findings did not support our hypothesis. We found that bidirectional, but not large, performance errors limited generalization across contexts, which could be mediated by two distinct mechanisms. On the one hand, bidirectional errors upon removal of the split-perturbation are also experienced when transitioning to overground walking. Thus, bidirectional errors may facilitate switching between distinct walking patterns, thereby limiting generalization. On the other hand, large unidirectional errors induce more motor adaptation, which might lead to more generalization.
Connectome-based predictive modeling of cognitive reserve using task-based functional connectivity
Authors: Boyle Rory , Connaughton Michael , McGlinchey Eimear , Knight Silvin P. , De Looze Céline , Carey Daniel , Stern Yaakov , Robertson Ian H. , Kenny Rose Anne , Whelan Robert
Published: June 2022

Cognitive reserve supports cognitive function in the presence of pathology or atrophy. Functional neuroimaging may enable direct and accurate measurement of cognitive reserve which could have considerable clinical potential. The present study aimed to develop and validate a measure of cognitive reserve using task-based fMRI data that could then be applied to independent resting-state data. Connectome-based predictive modeling with leave-one-out cross-validation was applied to predict a residual measure of cognitive reserve using task-based functional connectivity from the Cognitive Reserve/Reference Ability Neural Network studies (n = 220, mean age = 51.91 years, SD = 17.04 years). Three network-strength predicted cognitive reserve measures were generated that accurately predicted the residual measures of unseen participants. The theoretical validity of these measures was established via a positive correlation with a socio-behavioural proxy of cognitive reserve (verbal intelligence) and a positive correlation with global cognition, independent of brain structure. This fitted model was then applied to external test data: resting-state functional connectivity data from The Irish Longitudinal Study on Ageing (TILDA, n = 294, mean age = 68.3 years, SD = 7.18 years). The network-strength predicted measures were not positively associated with a residual measure of cognitive reserve nor with measures of verbal intelligence and global cognition. The present study demonstrated that task-based functional connectivity data can be used to generate theoretically valid measures of cognitive reserve. Further work is needed to establish if, and how, measures of cognitive reserve derived from task-based functional connectivity can be applied to independent resting-state data.
Variable Number Tandem Repeats (VNTRs) as modifiers of breast cancer risk in carriers of BRCA1 185delAG
Authors: Ding Yuan Chun , Adamson Aaron W. , Bakhtiari Mehrdad , Patrick Carmina , Park Jonghun , Laitman Yael , Weitzel Jeffrey N. , Bafna Vineet , Friedman Eitan , Neuhausen Susan L.
Published: June 2022

Despite substantial efforts in identifying both rare and common variants affecting disease risk, in the majority of diseases, a large proportion of unexplained genetic risk remains. We propose that variable number tandem repeats (VNTRs) may explain a proportion of the missing genetic risk. Herein, we tested whether VNTRs are causal modifiers of breast cancer risk in 347 female carriers of BRCA1 185delAG, an important group given their high risk of developing breast cancer. We performed targeted-capture to sequence VNTRs, called genotypes with adVNTR, and tested the association of VNTRs and breast cancer risk using Cox regression models. Of 303 VNTRs that passed quality control checks, 4 VNTRs were significantly associated with risk to develop breast cancer at false discovery rate [FDR] < 0.05 and an additional 4 VNTRs had FDR < 0.25. After determining the specific risk alleles, there was a significantly earlier age at development of breast cancer in carriers of the risk genotypes compared to those without the risk genotypes for seven of eight VNTRs. Results from this first systematic study of VNTRs demonstrate that VNTRs may explain a proportion of the unexplained genetic risk for disease and have larger effects than SNPs.
RBFOX2 deregulation promotes pancreatic cancer progression and metastasis through alternative splicing
Authors: Maurin Michelle , Ranjouri Mohammadreza , Martin Katelyn , Miner Robert , Newberg Justin Y. , Du Dongliang , Centeno Barbara , Fleming Jason B. , Yu Xiaoqing , Guccione Ernesto , Black Michael A. , Mann Karen M.
Published: June 2022

RNA splicing is an important biological process associated with cancer initiation and progression, yet in pancreatic cancer the role and regulation of splicing is not well understood. From a forward genetic screen in a mouse model of pancreatic cancer, we identified an enrichment of RNA binding proteins (RBPs) associated with the spliceosome. Here, we link deregulation of RBFOX2, an RBP of the FOX family, to pancreatic cancer progression and liver metastasis. We show that RBFOX2 regulation in pancreatic cancer occurs at both the RNA and protein level, and that nuclear localization of RBFOX2 is significantly reduced in poorly differentiated PDAC. Deregulation of RBFOX2 in PDAC is associated with an enrichment of exon exclusion events in transcripts encoding proteins involved in cytoskeletal remodeling and invadopodia programs that potentiate metastatic potential in vivo. Using splice-switching antisense oligonucleotides (AONs) and inducible cDNA isoforms, we demonstrate that RBFOX2 mediated exon exclusion in ABI1 controls the abundance and localization of ABI1 protein isoforms in pancreatic cancer cells, and that ABI1 splice-switching enhances cellular phenotypes associated with cancer cell stemness. Together, our data identify a novel role for RBFOX2 deregulation in promoting PDAC progression through alternative splicing regulation.
Independently ambulatory children with spina bifida experience near-typical joint moments and forces during walking
Authors: Lee Marissa R. , Hicks Jennifer L. , Wren Tishya A. L. , Delp Scott L.
Published: June 2022

Background

Spina bifida, a neurological defect, can result in lower-limb muscle weakness. Altered ambulation and reduced musculoskeletal loading can yield decreased bone strength in individuals with spina bifida, yet individuals who remain ambulatory can exhibit normal bone outcomes.

Research question

During walking, how do lower-limb joint kinematics, moments, and forces in independently ambulatory children with spina bifida differ from those of children with typical development?

Methods

We retrospectively analyzed data from 16 independently ambulatory children with spina bifida and 16 children with typical development and confirmed that bone strength was similar between the two groups. Plantar flexor muscle strength was measured by manual muscle testing, and 14 of the children with spina bifida wore activity monitors for one week. We estimated joint forces using motion capture data and musculoskeletal simulations. We used Statistical Parametric Mappingt-tests to compare lower-limb joint kinematic and kinetic waveforms between the groups with spina bifida and typical development. Within the group with spina bifida, we examined relationships between plantar flexor muscle strength and peak tibial forces by calculating Spearman correlations.

Results

Activity monitors from the children with spina bifida reported typical daily steps (9656 [SD 3095]). Despite slower walking speeds (p=0.004) and altered lower-body kinematics (p<0.0001), children with spina bifida had joint moments and forces similar to those of children with typical development, with no detectable differences during stance. Plantar flexor muscle weakness was associated with increased compressive knee force (p=0.001) and shear ankle force (p=0.006).

Significance

High-functioning, independently ambulatory children with spina bifida exhibited near-typical bone strength and near-typical step counts and load magnitudes. Our results suggest that maintaining ambulation and muscle strength can promote bone health in this population.

Highlights

Gait analysis was performed in high-functioning children with spina bifida

On average, these children had typical knee & ankle moments & forces during walking

Weak plantar flexor muscles were associated with increased tibial forces