bluuebunny/crossref_metadata_2025 huggingface dataset:
Interleukin 18 (IL-18) and IL-3 in Extracellular Vesicles: Biomarkers for Durable Elite Control of HIV-1
Authors: Poveda Eva , Fitzgerald Wendy , Reglero Cristina , Pérez-González Alexandre , Mariño Ana , Álvarez Hortensia , Valcarce Nieves , Llibre Josep Maria , Guillén Santiago Moreno , Muñoz Fernández Maria Angeles , Ruiz-Mateos Ezequiel , Margolis Leonid , Lederman Michael M , Freeman Michael L
Published: February 2023

Plasma extracellular vesicle (EV)-associated cytokines were quantified in people with HIV (PWH) with different virological control status, including elite controllers (EC) who maintain persistent control (PC) or not (TC). Cytokine signatures and pathways were determined for each group. Median EV-associated cytokine levels were higher among PWH than HIV-uninfected. EC showed the highest levels of EV-associated cytokines among PWH with PC levels higher than TC levels. IL-18 levels best distinguished PWH from uninfected controls, and EC from ART-treated, and IL-3 distinguished PC from TC. The role of EV-cytokines in intercellular communication and endogenous control of HIV expression should be investigated further.
The lymphatic endothelium-derived follistatin: activin A axis regulates neutrophil motility in response to Pseudomonas aeruginosa
Authors: McMinn Patrick H , Ahmed Adeel , Huttenlocher Anna , Beebe David J , Kerr Sheena C
Published: February 2023

The lymphatic system plays an active role during infection, however the role of lymphatic-neutrophil interactions in host-defense responses is not well understood. During infection with pathogens such as Pseudomonas aeruginosa, Staphylococcus aureus and Yersinia pestis, neutrophils traffic from sites of infection through the lymphatic vasculature, to draining lymph nodes to interact with resident lymphocytes. This process is poorly understood, in part, due to the lack of in vitro models of the lymphatic system. Here we use a 3D microscale lymphatic vessel model to examine neutrophil–lymphatic cell interactions during host defense responses to pathogens. In previous work, we have shown that follistatin is secreted at high concentrations by lymphatic endothelial cells during inflammation. Follistatin inhibits activin A, a member of the TGF-β superfamily, and, together, these molecules form a signaling pathway that plays a role in regulating both innate and adaptive immune responses. Although follistatin and activin A are constitutively produced in the pituitary, gonads and skin, their major source in the serum and their effects on neutrophils are poorly understood. Here we report a microfluidic model that includes both blood and lymphatic endothelial vessels, and neutrophils to investigate neutrophil-lymphatic trafficking during infection with P. aeruginosa. We found that lymphatic endothelial cells produce secreted factors that increase neutrophil migration toward P. aeruginosa, and are a significant source of both follistatin and activin A during Pseudomonas infection. We determined that follistatin produced by lymphatic endothelial cells inhibits activin A, resulting in increased neutrophil migration. These data suggest that the follistatin:activin A ratio influences neutrophil trafficking during infection with higher ratios increasing neutrophil migration.
Sex-, age-, and time-specific visual communication in brown bears
Authors: Penteriani Vincenzo , Etchart Léa , González-Bernardo Enrique , Hartasánchez Alfonso , Falcinelli Daniele , Ruiz‑Villar Héctor , Morales‑González Ana , Delgado María del Mar
Published: February 2023

Intraspecific communication in mammals is well-documented but generally restricted to chemical and acoustic signaling. However, other overlooked channels, such as visual signaling, may be used to communicate among conspecifics. Here, by using experimental manipulations together with camera traps on 13 brown bear (Ursus arctos) rubbing trees in the Cantabrian Mountains (northwestern Spain), we document detailed temporal patterns and behavioral aspects of a recently discovered novel communication channel for this species, visual signaling through the trunk debarking of focal trees. Video footage showed that visual marking is a sex-, age-, and time-specific means of communication in brown bears, being performed exclusively by adult males during the mating season (mainly April–June in the study area). Trunk debarking was always associated with chemical marking and was never an isolated behavior, suggesting that visual and chemical signals might be complementary. Visual and chemical marks may provide different information; for example, visual marks could be an indicator of individual size and, thus, the dominance status of adult males looking for mating opportunities. This is the first time that evidence is provided showing that visual signaling in a large carnivore is exclusive to a specific class of individuals (adult males) and linked to reproductive needs only. Bear visual signaling not only represents an advance in our comprehension of animal communication but may also serve to easily locate the mating areas of mammals, which are crucial for large carnivore species, such as the brown bear, that frequently need specific and urgent plans for conservation and management.
Living With Physical Health Conditions: A Systematic Review of Mindfulness-Based Interventions for Children, Adolescents, and Their Parents
Authors: Hughes Olivia , Shelton Katherine H , Penny Helen , Thompson Andrew R
Published: February 2023

Objectives

This systematic review aimed to identify and appraise studies investigating the efficacy of mindfulness-based interventions (MBIs) for improving depression, anxiety and parental stress in families affected by childhood physical illnesses, as well as feasibility and acceptability.

Methods

Embase, PsycINFO, Scopus, Medline, and PubMed were searched between February 2 and 17, 2021, and updated on August 5, 2022. Studies investigating MBIs with children and adolescents (<18 years) with physical health conditions were included, and results are presented with narrative synthesis.

Results

Eighteen studies met eligibility criteria. Studies included children and adolescents with chronic pain, headaches, cancer, heart conditions, esophageal atresia, inflammatory bowel disease, and polycystic ovary syndrome. Most studies reported mindfulness was feasible and acceptable, although findings for different health conditions were mixed. Some studies encountered difficulties with attrition, resulting in findings being underpowered.

Conclusions

MBIs show promise for improving anxiety and depression in children with physical health conditions, but there is limited support for reducing stress in the family unit. A potential direction for future research might be the inclusion of parents. However, because of the heterogeneity of studies included in this review, findings must be cautiously interpreted.
Stress-induced deeper rooting introgression enhances wheat yield under terminal drought
Authors: Bacher Harel , Montagu Aviad , Herrmann Ittai , Walia Harkamal , Schwartz Nimrod , Peleg Zvi
Published: February 2023

Water scarcity is the primary environmental constraint affecting wheat growth and production and is increasingly exacerbated due to climatic fluctuation, which jeopardizes future food security. Most breeding efforts to improve wheat yields under drought have focused on above-ground traits. Root traits are closely associated with various drought adaptability mechanisms, but the genetic variation underlying these traits remains untapped, even though it holds tremendous potential for improving crop resilience. Here, we examined this potential by re-introducing ancestral alleles from wild emmer wheat (Triticum turgidum ssp. dicoccoides) and studied their impact on root architecture diversity under terminal drought stress. We applied an active sensing electrical resistivity tomography approach to compare a wild emmer introgression line (IL20) and its drought-sensitive recurrent parent (Svevo) under field conditions. IL20 exhibited greater root elongation under drought, which resulted in higher root water uptake from deeper soil layers. This advantage initiated at the pseudo-stem stage and increased during the transition to the reproductive stage. The increased water uptake promoted higher gas exchange rates and enhanced grain yield under drought. Overall, we show that this presumably ‘lost’ drought-induced mechanism of deeper rooting profile can serve as a breeding target to improve wheat productiveness under changing climate.
Dancing at the Hotel Adlon: Queer, Black, and Jewish Characters in Contemporary German Television
Authors: Gollance Sonia
Published: February 2023

This article discusses Das Adlon: Eine Familiensaga (Hotel Adlon: A Family Saga), a 2013 German miniseries about one of the most exclusive addresses in Germany’s capital. This miniseries about the quintessentially upper-class German location chooses to portray minority characters whose story arcs are developed through dance scenes that reveal the complexity of representing queer, Black, and Jewish characters in a miniseries designed for mass consumption. In this way, the miniseries and its dance scenes raise important questions about who belongs in Germany. I contend that the dance floor is an arena through which the miniseries Hotel Adlon and its characters negotiate changing notions of what it means to be German.
Maternal Tobacco Smoking During Pregnancy and Children’s Emotional and Behavioral Trajectories: The EDEN Mother–Child Birth Cohort Study
Authors: Bonello Kim , Gomajee Ramchandar , Ibanez Gladys , Martins Silvia , Keyes Katherine , Nakamura Aurélie , Lepeule Johanna , Strandberg-Larsen Katrine , Fekom Mathilde , Melchior Maria
Published: February 2023

Introduction

The nature of the relationship between maternal tobacco smoking during pregnancy and the occurrence of children’s behavioral problems is still a matter of controversy. We tested this association using data collected among a sample of pregnant women and their offspring followed up from birth to early adolescence (age 12 years), accounting for multiple parent, child, and family characteristics.

Aims and Methods

Data come from 1424 mother–child pairs participating in the Étude des Déterminants pré et post-natals précoces du développement psychomoteur et de la santé de l’ENfant mother–child cohort in France. Using repeated measures (3, 5.5, 8, and 11.5 years) of the mother-reported Strengths and Difficulties Questionnaire, we estimated trajectories of children’s emotional and behavioral difficulties. Two aspects of maternal smoking were studied: The timing (nonsmoker, smoking during the periconceptional period, or throughout pregnancy) and the level of use (cigarettes/day) during the first trimester of pregnancy. Robust Poisson regression models controlled for confounding factors including maternal mental health and socioeconomic characteristics using propensity scores with the overlap weighting technique.

Results

Contrary to bivariate analyses, in propensity score–controlled regression models, maternal smoking throughout pregnancy was no longer significantly associated with offspring emotional or behavioral difficulties. Maternal heavy smoking (≥10 cigarettes/day) remained significantly associated with intermediate levels of conduct problems (RR 1.25, 95% CI 1.19 to 1.31).

Conclusions

The association between maternal smoking in pregnancy and offspring’s emotional and behavioral difficulties appears to be largely explained by women’s other characteristics. However, maternal heavy smoking appears to be related to offspring behavioral difficulties beyond the role of confounding characteristics.

Implications

The relationship between maternal smoking during pregnancy (in two modalities: Timing and level of smoking) and behavioral difficulties in children is still a matter of debate. While the relationship between any maternal tobacco use and offspring behavioral difficulties appears to be largely explained by confounding factors, heavy maternal smoking in the first trimester of pregnancy seems to be associated with offspring behavioral difficulties beyond the socioeconomic and mental health characteristics transmitted across generations.
Boosting UPR transcriptional activator XBP1 accelerates acute wound healing
Authors: Wang Jie-Mei , Li Hainan , Xu Liping , Kim Hyunbae , Qiu Yining , Zhang Kezhong
Published: February 2023

Patients’ suffering from large or deep wounds caused by traumatic and/or thermal injuries have significantly lower chances of recapitulating lost skin function through natural healing. We tested whether enhanced unfolded protein response (UPR) by expression of a UPR transcriptional activator, X-box-binding protein 1 (XBP1) can significantly promote wound repair through stimulating growth factor production and promoting angiogenesis. In mouse models of a second-degree thermal wound, a full-thickness traumatic wound, and a full-thickness diabetic wound, the topical gene transfer of the activated form of XBP1 (spliced XBP1, XBP1s) can significantly enhance re-epithelialization and increase angiogenesis, leading to rapid, nearly complete wound closure with intact regenerated epidermis and dermis. Overexpression of XBP1s stimulated the transcription of growth factors in fibroblasts critical to proliferation and remodeling during wound repair, including platelet-derived growth factor BB, basic fibroblast growth factor, and transforming growth factor beta 3. Meanwhile, the overexpression of XBP1s boosted the migration and tube formation of dermal microvascular endothelial cells in vitro. Our functional and mechanistic investigations of XBP1-mediated regulation of wound healing processes provide novel insights into the previously undermined physiological role of the UPR in skin injuries. The finding opens an avenue to developing potential XBP1-based therapeutic strategies in clinical wound care protocols.
Eternally Damned, Yet Socially Conscious? The Volunteerism of Canadian Atheists
Authors: Speed David , Edgell Penny
Published: February 2023

Research suggests that people who are religious may volunteer because religion is innately prosocial (i.e., inclination) or perhaps because religious communities provide volunteering chances (i.e., opportunities). Using data from Statistics Canada (General Social Survey, Cycle 33), we explored the relationship between different religious and nonreligious identities and volunteering behaviors, time commitments to volunteering, and organization types for which respondents volunteered. Results indicated a complex relationship between religious/nonreligious identity, religious attendance, and prayer. We found that (1) atheists were more likely to volunteer than religious individuals who were low on religious attendance; (2) atheists were less likely to volunteer than religious individuals who were high on religious attendance; (3) the difference in volunteering between atheists and religious individuals was driven by the latter’s volunteering in a religious context, not in the broader community. The results suggest that atheists likely have fewer opportunities to volunteer but are similarly inclined to volunteer.
A pragmatic framework for the application of new approach methodologies in one health toxicological risk assessment
Authors: Magurany Kelly A , Chang Xiaoqing , Clewell Rebecca , Coecke Sandra , Haugabrooks Esther , Marty Sue
Published: February 2023

Globally, industries and regulatory authorities are faced with an urgent need to assess the potential adverse effects of chemicals more efficiently by embracing new approach methodologies (NAMs). NAMs include cell and tissue methods (in vitro), structure-based/toxicokinetic models (in silico), methods that assess toxicant interactions with biological macromolecules (in chemico), and alternative models. Increasing knowledge on chemical toxicokinetics (what the body does with chemicals) and toxicodynamics (what the chemicals do with the body) obtained from in silico and in vitro systems continues to provide opportunities for modernizing chemical risk assessments. However, directly leveraging in vitro and in silico data for derivation of human health-based reference values has not received regulatory acceptance due to uncertainties in extrapolating NAM results to human populations, including metabolism, complex biological pathways, multiple exposures, interindividual susceptibility and vulnerable populations. The objective of this article is to provide a standardized pragmatic framework that applies integrated approaches with a focus on quantitative in vitro to in vivo extrapolation (QIVIVE) to extrapolate in vitro cellular exposures to human equivalent doses from which human reference values can be derived. The proposed framework intends to systematically account for the complexities in extrapolation and data interpretation to support sound human health safety decisions in diverse industrial sectors (food systems, cosmetics, industrial chemicals, pharmaceuticals etc.). Case studies of chemical entities, using new and existing data, are presented to demonstrate the utility of the proposed framework while highlighting potential sources of human population bias and uncertainty, and the importance of Good Method and Reporting Practices.
In colon cancer cells fascin1 regulates adherens junction remodeling
Authors: Esmaeilniakooshkghazi Amin , Pham Eric , George Sudeep P. , Ahrorov Afzal , Villagomez Fabian R. , Byington Michael , Mukhopadhyay Srijita , Patnaik Srinivas , Conrad Jacinta C. , Naik Monali , Ravi Saathvika , Tebbutt Niall , Mooi Jennifer , Reehorst Camilla M. , Mariadason John M. , Khurana Seema
Published: February 2023

Adherens junctions (AJs) are a defining feature of all epithelial cells. They regulate epithelial tissue architecture and integrity, and their dysregulation is a key step in tumor metastasis. AJ remodeling is crucial for cancer progression, and it plays a key role in tumor cell survival, growth, and dissemination. Few studies have examined AJ remodeling in cancer cells consequently, it remains poorly understood and unleveraged in the treatment of metastatic carcinomas. Fascin1 is an actin‐bundling protein that is absent from the normal epithelium but its expression in colon cancer is linked to metastasis and increased mortality. Here, we provide the molecular mechanism of AJ remodeling in colon cancer cells and identify for the first time, fascin1's function in AJ remodeling. We show that in colon cancer cells fascin1 remodels junctional actin and actomyosin contractility which makes AJs less stable but more dynamic. By remodeling AJs fascin1 drives mechanoactivation of WNT/β‐catenin signaling and generates “collective plasticity” which influences the behavior of cells during cell migration. The impact of mechanical inputs on WNT/β‐catenin activation in cancer cells remains poorly understood. Our findings highlight the role of AJ remodeling and mechanosensitive WNT/β‐catenin signaling in the growth and dissemination of colorectal carcinomas.
Pathological pseudoprogression to anti-PD-1 inhibitor in metastatic periampullary carcinoma: Case report
Authors: Wang Junhui , Wang Yan , Che Xiaoling
Published: February 2023

Rationale:

Pseudoprogression has been deemed as a rare clinical phenomenon during the treatment of immune checkpoint inhibitors in patients with advanced cancers, especially in periampullary carcinoma, however, leaving potential molecular mechanism remain unknown.

Patient concerns:

Regular examination after radical pancreaticoduodenectomy because of periampullary carcinoma.

Diagnoses:

Recurrent periampullary carcinoma with metastasis in liver.

Interventions:

Regimens of XELOX (oxaliplatin at a dose of 130 mg/m2, day 1 and oral capecitabine at a dose of 1000 mg/m2 twice a day, day 1–14, every 21 days), and tislelizumab at a dose of 200 mg, day 1, per 21 days, was prescribed as palliative treatment.

Outcomes:

Pseudoprogression and symptom of hair and mustache repigmentation were also observed, which resulted in partial response finally.

Lessons:

Results of the present case suggested that pseudoprogression, along with hair and mustache repigmentation, possibly caused by anti-PD-1 inhibitors, may also happen in patients with periampullary carcinoma, which should be paid attention to. The potential mechanism should be further investigated.
Predictors of long-term outcomes after catheter-directed thrombolysis combined with stent implantation in acute deep vein thrombosis secondary to iliac vein compression
Authors: Yu Feng , Wu Shuai , Chen Cong
Published: February 2023

The purpose of this study is to analyze predictive factors for long-term clinical outcomes after catheter-directed thrombolysis (CDT) combined with stent implantation for acute deep vein thrombosis (DVT) secondary to iliac vein compression (IVC). A retrospective analysis was performed to review clinical data and follow-up information on 52 patients who underwent CDT combined with stent implantation for acute DVT secondary to IVC from June 2015 to March 2020. Clinical outcomes including stent patency and incidence of postthrombotic syndrome (PTS) were investigated using Kaplan–Meier analysis. All included patients were categorized into 2 groups according to the presence of PTS. Potential risk factors, including age, gender, degree of iliac vein stenosis, time from onset to treatment, dosage of thrombolytic agent, stent extending below the inguinal ligament, and duration of anticoagulation for PTS were evaluated using multivariate logistic regression analysis. Over a median follow-up of 24 months, 4 individuals underwent reintervention due to in-stent stenosis or stent compression. Primary stent patency was 98.1% at 1 month, 94.2% at 6 months, 90.4% at 12 months, and 88.5% at 24 months. Freedom from PTS was 98.1% at 6 months, 84.6% at 12 months, and 75% at 24 months. No treatment-related mortality or morbidity was observed. Based on the development of PTS, 13 patients with PTS were classified into group A and 39 patients without PTS were regarded as group B. Upon multivariate logistic regression analysis, key prognostic factors for PTS were degree of iliac vein stenosis and time from onset to treatment. CDT combined with stent implantation is safe and effective for acute DVT secondary to IVC in the long-term perspective. Severe iliac vein stenosis and longer period from onset to treatment may be associated with a higher risk of PTS.
Hepatic failure in a patient with rheumatoid arthritis treated with methotrexate: A case report
Authors: Miyata Masayuki , Ishiwata Sho , Kuroda Masahito , Tasaki Kazuhiro , Migita Kiyoshi , Ohira Hiromasa
Published: February 2023

Introduction:

Chronic liver damage from methotrexate (MTX) is not uncommon, and fatal outcome is rare. We experienced a case of hepatic failure leading to death. We considered the cause of death through this case and proposed a method to prevent the progression of this liver injury.

Patient concerns:

We report the case of a patient with rheumatoid arthritis treated with MTX for 15 years.

Diagnosis, interventions, and outcomes:

A liver biopsy revealed histological changes similar to those of advanced nonalcoholic steatohepatitis (NASH), most likely induced by MTX. MTX was discontinued after 4 years. Two years after the discontinuation, the patient died of irreversible hepatic failure. Her obesity, complicated by type 2 diabetes mellitus, might have aggravated MTX-induced NASH-like liver injury.

Conclusion:

Early diagnosis and immediate MTX discontinuation following NASH diagnosis and strict type 2 diabetes mellitus control might have prevented the irreversible progression of liver injury.
The low glutamate diet reduces blood pressure in veterans with Gulf War Illness: A CONSORT randomized clinical trial
Authors: Fiebel Prairie R. , Ramachandra Shalini S. , Holton Kathleen F.
Published: February 2023

Background:

Gulf War Illness is a multi-symptom condition affecting veterans of the 1990 to 1991 Gulf War, which often presents with comorbid hypertension. The purpose of this study was to analyze the effects of the low glutamate diet, as well as an acute challenge of monosodium glutamate (MSG)/placebo, on resting heart rate, blood oxygenation level, and blood pressure (BP) in this population.

Methods:

These data were measured at 4 time points: baseline, after 1 month on the low glutamate diet, and during each challenge week, where subjects were randomized into a double-blind, placebo-controlled, crossover challenge with MSG/placebo over 3 days each week. Pre-post diet changes were analyzed using paired t tests, change in the percentage of veterans meeting the criteria for hypertension was compared using chi-square or Fisher exact tests, and crossover challenge results were analyzed using general linear modeling in SAS® 9.4.

Results:

There was a significant reduction in systolic BP (sitting and recumbent; both P < .001) and diastolic BP (sitting; P = .02) after 1 month on the diet. The percentage meeting the criteria for hypertension was also significantly reduced (P < .05). Challenge with MSG/placebo did not demonstrate an acute effect of glutamate on blood pressure.

Conclusion:

Overall, these findings suggest that the low glutamate diet may be an effective treatment for lowering blood pressure in veterans with Gulf War Illness. This dietary effect does not appear to be driven by reduced consumption of free glutamate, but rather, by an increase in consumption of non-processed foods.
Efficacy of probiotics on nonalcoholic fatty liver disease: A meta-analysis
Authors: Zhou Xiangyu , Wang Jincheng , Zhou Sufang , Liao Jiajia , Ye Zuoyu , Mao Leiming
Published: February 2023

Objectives:

The intestinal flora is closely related to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). This study intends to systematically evaluate the efficacy and safety of probiotics in the treatment of NAFLD through a meta-analysis of published randomized controlled trials.

Methods:

This study was conducted through a search of published randomized controlled trials using probiotic-related drugs for the treatment of nonalcoholic fatty liver disease (up to April 6, 2022). The JADAD evaluation table was used to evaluate the quality of the literatures included in the search, and the risk of bias was evaluated according to the Cochrane evaluation manual. Finally, RevMan5.4 software was used for meta-analysis.

Results:

A total of 21 randomized clinical trials involving 1037 patients with NAFLD were included in this study. Meta-analysis results showed that after probiotic intervention, liver function, blood lipid level, blood glucose levels and insulin levels were significantly reduced, which had a good effect on improving hepatic steatosis. However, it did not significantly improve BMI, inflammatory factors, or homeostasis model assessment of insulin resistance. Through the subgroup analysis of the course of treatment, it was found that ALT, GGT, TG, and blood sugar improved better in the probiotic treatment course of greater than or equal to 12 weeks.

Conclusion:

This study shows that the use of probiotics therapy has a good regulating effect on liver function, steatosis, blood glucose level, insulin level and blood lipid level in NAFLD patients.
Efficiency of virtual reality for cardiopulmonary resuscitation training of adult laypersons: A systematic review
Authors: Alcázar Artero Petronila Mireia , Pardo Rios Manuel , Greif Robert , Ocampo Cervantes Ana Belén , Gijón-Nogueron Gabriel , Barcala-Furelos Roberto , Aranda-García Silvia , Ramos Petersen Laura
Published: February 2023

Background:

Virtual reality (VR) is an interesting and promising way to teach cardiopulmonary resuscitation (CPR) to adult laypersons as its high immersive characteristics could improve the level of skills and acquired knowledge in learning basic life support (BLS).

Methods:

This systematic review assesses current literature about BLS training with VR and its possible effect on CPR-quality parameters, self-efficacy, perceived learning, and learners’ satisfaction and short and long-term patients’ outcome. We screened the Cochrane Library, PubMed, CINAHL, MEDLINE Ovid, Web of Science, and Scopus databases and included only clinical trials and quasi-experimental studies published from inception to October 1, 2021, which analyzed adult laypersons’ BLS training with the use of VR. Primary outcomes were CPR parameters (chest compression rate and depth, Automated External Defibrillator use). Secondary outcomes were self-efficacy, perceived learning and learners satisfaction, and patients’ outcomes (survival and good neurologic status). The risk of bias of included study was assessed using the Cochrane Handbook for Systematic Reviews of Interventions tool to evaluate randomized control trials and the transparent reporting of evaluations with nonrandomized designs checklist for nonrandomized studies.

Results:

After full article screening, 6 studies were included in the systematic review (731 participants) published between 2017 and 2021. Because of the heterogeneity of the studies, we focused on describing the studies rather than meta-analysis. The assessment of the quality of evidence revealed overall a very low quality. Training with VR significantly improved the rate and depth of chest compressions in 4 out of 6 articles. VR was described as an efficient teaching method, exerting a positive effect on self-efficacy, perception of confidence, and competence in 2 articles.

Conclusion:

VR in BLS training improves manual skills and self-efficacy of adult laypersons and may be a good teaching method in a blended learning CPR training strategy. VR may add another way to divide complex parts of resuscitation training into easier individual skills. However, the conclusion of this review suggests that VR may improve the quality of the chest compressions as compared to instructor-led face-to-face BLS training.
The yield of neuroimaging in patients presenting to the emergency department with isolated neuro-ophthalmological complaints: A retrospective chart review
Authors: El Zahran Tharwat , El Hadi Dalia , Mostafa Hala , Mansour Hana , Hashim Ibrahim , Tahhan Soubhi , Bou Ghannam Alaa
Published: February 2023

Neuro-ophthalmological emergencies require prompt assessment and management to avoid vision or life-threatening sequelae. The decision to perform a neuroimaging procedure is based on the clinical judgment of the medical team, without defined indications. This study aims to identify presenting symptoms and physical exam findings associated with relative positive findings on neuroimaging studies. Electronic medical records of patients presenting to the emergency department (ED) with isolated neuro-ophthalmologic complaints between January 1, 2013 and September 30, 2019 were reviewed. We collected data on the clinical presentation, neuroimaging procedures and results, consults, and diagnoses. Two hundred eleven patients’ charts were reviewed. Most presented with unilateral eye complaints (53.6%), and the most common symptoms were blurred vision (77.3%) and headaches (42.2%). A total of 126 imaging procedures were performed of which 74.6% were normal, while 25.4% showed relevant abnormal findings. Complaining of blurry vision (P = .038) or visual field changes (P = .014) at presentation as well as having a visual field defect (P = .016), abnormal pupil reactivity (P = .028), afferent pupillary defect (P = .018), or abnormal optic disc exam (P = .009) were associated with positive findings on imaging. Neuroimaging is more likely to yield positive findings in patients presenting to the ED with visual field irregularities, afferent pupillary defects, or abnormal optic discs. These findings – when combined with the proper clinical setting – should lower the threshold to proceed with neuroimaging in the emergency department. Based on our results, larger-scale studies might lead to a well-structured algorithm to be followed by ED physicians in decision making.
Left atrial deformation and risk of transient ischemic attack and stroke in patients with paroxysmal atrial fibrillation
Authors: Chen Jian , Zhao Ying , Ma Changsheng , Du Xin , He Yihua , Li Hong
Published: February 2023

Left atrial (LA) remodeling is closely related to the occurrence of cerebral stroke; however, the relationship between early-stage impaired deformability of the left atrium and stroke/transient ischemic attack (TIA) remains unclear. The aim of this study was to evaluate the changes in LA deformability and to assess its relationship with stroke/TIA events using speckle tracking echocardiography. A total of 365 patients with paroxysmal atrial fibrillation (non-stroke/TIA [n = 318]; stroke/TIA [n = 47]) underwent comprehensive echocardiography with speckle tracking imaging to calculate mean LA longitudinal strain and strain rate values from apical 4-chamber, 2-chamber, and 3-chamber views. The stroke/TIA group was older, had a greater proportion of males, and had lower LA strain rate during left ventricular early diastole (SRE), and the difference was statistically significant (P < .05). On univariate linear regression analysis, the following clinical and conventional echocardiographic parameters showed a significant linear correlation (P < .001) with SRE: E/A ratio; LA volume index (VI); body mass index; mean E/e′; left ventricular ejection fraction; age; and hypertension. Multiple linear regression analysis revealed a linear dependence between SRE and E/A ratio, LA VI, and body mass index. The regression equation was y = −1.430–0.394X1 + 0.012X2 + 0.019X3 (P < .001) (y, SRE; X1, E/A ratio; X2, LA VI; X3, body mass index). In multivariate logistic regression analyses, SRE and sex ratio were independent risk factors for stroke/TIA (SRE, odds ratio 2.945 [95% confidence interval 1.092–7.943]; P = .033; sex, odds ratio 0.462 [95% confidence interval 0.230–0.930]; P = .031). Among patients with paroxysmal atrial fibrillation, SRE reflected impaired deformability of the left atrium in the early stages and was associated with the risk of stroke/TIA.
Trends of denosumab-related publications in web of science
Authors: Jiang Xiaohong , Xie Tianyu , Feng Wenyu , Qin Zhaojie , Liao Shijie , Liu Yun , Lu Shenglin , He Mingwei , Wei Qingjun
Published: February 2023

Denosumab is a human monoclonal antibody that targets nuclear factor-kappa B ligand and is highly effective in blocking bone resorption. Bibliometrics can intuitively show the research development process, research status, research hotspots and development trend of a certain topic for researchers. This study assessed the course of research and development for denosumab in terms of publications over the past 2 decades. Web of Science databases were searched to identify publications related to research on denosumab from January 1, 2005 to December 31, 2022. The VOS Viewer software (version 1.6.17) and Bibliometrix package in R (version 4.1.3) were used in this study. There were 5119 denosumab-related publications during this period. The total number of citations of denosumab-related publications reached 94917. The most articles were published in the field of Endocrinology Metabolism. As an international language, English remains the most popular language for writing papers. Five of the top ten institutions originated in the USA. Through the VOS Viewer analysis, we found that the relationships between Amgen Inc. with its collaborations were grouped into 4 clusters, the USA was the mainland for research and development on denosumab, closely collaborating with many other countries, such as Canada, Japan, England, and China. Wagman RB from USA was the most prolific author with 119 publications. The journal with the most publications was Osteoporosis International (481 publications). The most cited article was “Denosumab for Prevention of Fractures in Postmenopausal Women with Osteoporosis” with 2053 citations. The clinical trial comprised 6 of the 10 most frequently cited publications, and the rest consisted of reviews. The most frequent keywords for publications since January 1, 2014 were “prevention” and “management,” indicating that a number of prevention and management measures have been developed to regulate the use of denosumab in treating osteoporosis. Our research provided a comprehensive review of denosumab-related publications, suggesting that the development of denosumab is a long process and numerous clinical trials have been conducted before applications in clinical settings.
Optical coherence tomography classifications of diabetic macular edema and response to aflibercept: One-year follow-up outcomes in a Chinese population
Authors: Gu Zheyao , Xi Ting , Zhang Chunyuan , Yang Guang
Published: February 2023

To evaluate the effect of intravitreal aflibercept on different classifications of diabetic macular edema (DME) by spectral-domain optical coherence tomography. This hospital-based retrospective study included 95 consecutive patients (130 eyes) diagnosed with DME. Three groups were defined: diffuse retinal thickening (DRT), cystoid macular edema and serous retinal detachment. All eyes received intravitreal aflibercept (0.05 mL/2 mg) 5 times monthly. Best corrected visual acuity (BCVA) in (logarithm of the minimum angle of resolution) units and central macular thickness (CMT) on optical coherence tomography were recorded at months 1, 2, 3, 4, 6, and 12 after the injections. There was no significant baseline difference in BCVA (P = .273) or CMT (P = .115) among the 3 groups. Over 12 months, the BCVA of the DRT group significantly improved from baseline (P = .013). The BCVA of the cystoid macular edema (P = .062) and serous retinal detachment groups (P = .073) improved slightly from baseline. The DRT group had the greatest BCVA improvement (P = .021). Over 12 months, the CMTs of all 3 groups significantly decreased from baseline (P = .016, P = .025, P = .031). The CMT decreased more in the DRT group than in the other 2 groups (P = .009). The CMT changes were most evident in the DRT group (P = .022). Binary logistic regression analysis showed that DME type, disorganization of the retinal inner layers, ellipsoid zone disruption and external limiting membrane disruption independently predicted the effect of aflibercept treatment in DME patients (P = .006, P = .001, P = .004, P = .001). Aflibercept therapy improved anatomical structure and visual acuity in every type of DME; DRT responded best in terms of both BCVA and CMT. Furthermore, DME, disorganization of the retinal inner layers, external limiting membrane disruption and ellipsoid zone disruption independently predicted the effect of aflibercept treatment in DME patients.
Oral Care Associated With Less Microaspiration in Ventilated Cardiac Patients
Authors: Patel Nishant , Lin Philip , Stack Michael , Conrad Janet M. , Fakioglu Harun , Abomoelak Bassam , Horvath Karoly , Mehta Devendra I.
Published: February 2023

Background and Objective:

Aspiration is common in mechanically ventilated patients and may predispose patients to aspiration pneumonia, chemical pneumonitis, and chronic lung damage. Pepsin A is a specific marker of gastric fluid aspiration and is often detected in ventilated pediatric patients. We investigated the effect of oral care and throat suctioning in the detection of pepsin A in tracheal aspirates (TAs) up to 4 hours after these procedures.

Methods:

Twelve pediatric patients between age 2 weeks to 14 years who underwent intubation for cardiac surgery were enrolled in this study. Six of the 12 patients were consented before their surgery with initial specimen collected at the time of intubation and last one shortly before extubation (intubation duration < 24 hours). The remaining 6 patients were consented after cardiac surgery. All specimens were collected per routine care per respiratory therapy protocol and shortly before extubation (intubation duration > 24 hours). Tracheal fluid aspirates were collected every 4 to 12 hours in the ventilated patients. Enzymatic assay for gastric pepsin A and protein determination were performed. The time of oral care and throat suctioning within 4 hours prior was recorded prospectively.

Results:

A total of 342 TA specimens were obtained from the 12 intubated pediatric patients during their course of hospitalization; 287 (83.9%) showed detectable total pepsin (pepsin A and C) enzyme activity (> 6 ng/mL) and 176 (51.5%) samples had detectable pepsin A enzyme levels (>6 ng/mL of pepsin A). Only 29 samples of 76 samples (38.2%) had evidence of microaspiration after receiving oral care, while 147 of 266 (55.3%) samples were pepsin A positive when no oral care was provided. Odds ratio is 0.50 (Cl 0.30–0.84), and the number needed to treat is 5.8 (Confidence interval 3.4–22.3). Testing air filters for pepsin was not beneficial.

Conclusion:

Oral care is a highly effective measure to prevent microaspiration of gastric fluid in ventilated pediatric patients. The number needed to treat (5.8) suggests this is a very effective prevention strategy. Our study suggests that pepsin A is a useful and sensitive biomarker that allows identification of gastric aspiration.
Methods for Mediation Analysis with High-Dimensional DNA Methylation Data: Possible Choices and Comparison
Authors: Clark-Boucher Dylan , Zhou Xiang , Du Jiacong , Liu Yongmei , Needham Belinda L , Smith Jennifer A , Mukherjee Bhramar
Published: February 2023

Epigenetic researchers often evaluate DNA methylation as a mediator between social/environmental exposures and disease, but modern statistical methods for jointly evaluating many mediators have not been widely adopted. We compare seven methods for high-dimensional mediation analysis with continuous outcomes through both diverse simulations and analysis of DNAm data from a large national cohort in the United States, while providing an R package for their implementation. Among the considered choices, the best-performing methods for detecting active mediators in simulations are the Bayesian sparse linear mixed model by Song et al. (2020) and high-dimensional mediation analysis by Gao et al. (2019); while the superior methods for estimating the global mediation effect are high-dimensional linear mediation analysis by Zhou et al. (2021) and principal component mediation analysis by Huang and Pan (2016). We provide guidelines for epigenetic researchers on choosing the best method in practice and offer suggestions for future methodological development.
Psychometric Properties of the NIH Toolbox Cognition and Emotion Batteries Among Children and Adolescents with Congenital Heart Defects
Authors: Wallace Julia , Ceschin Rafael , Lee Vince K. , Beluk Nancy H. , Burns Cheryl , Beers Sue , Lo Cecilia , Panigrahy Ashok , Badaly Daryaneh
Published: February 2023

Objective

The NIH Toolbox offers brief, computerized measures of cognitive and psychosocial functioning. However, its psychometric properties were established among typically developing children and adolescents. The current study provides the first comprehensive assessment of its psychometric properties among young patients with congenital heart defects (CHD).

Study Design

We prospectively recruited 58 patients with CHD and 80 healthy controls between the ages of 6 and 17. Participants completed the NIH Toolbox Cognition and Emotion Batteries, a battery of clinician-administered neuropsychological tests, and ratings of their quality of life. Their parents also completed ratings of their functioning.

Results

On the Cognition Battery, we found expectable group differences and developmentally expected gains across ages. For the most part, composites and subtests were significantly correlated with neuropsychological measures of similar constructs. Higher scores were generally associated with ratings of better day-to-day functioning among children with CHD. On the Emotion Battery, we found no significant group differences, echoing prior research. For the most part, scales showed acceptable internal consistency among both groups. There was adequate construct coherence for most of questionnaires among healthy control but not participants with CHD. Correlations with a comparison tool were largely within expectable directions.

Conclusion

The NIH Toolbox may provide a valid and useful assessment of cognitive functioning among children and adolescents with CHD. While it may offer reliable and valid scales of psychosocial functioning, further research is needed to understand the meaningfulness of the scales for participants with CHD.
Aneurysmal Growth in Type-B Aortic Dissection: Assessing the Impact of Patient-Specific Inlet Conditions on Key Haemodynamic Indices
Authors: Stokes C. , Ahmed D. , Lind N. , Haupt F. , Becker D. , Hamilton J. , Muthurangu V. , Tengg-Kobligk H. von , Papadakis G. , Balabani S. , Díaz-Zuccarini V.
Published: February 2023

Type-B Aortic Dissection is a cardiovascular disease in which a tear develops in the intimal layer of the descending aorta, allowing pressurized blood to delaminate the layers of the vessel wall. In medically managed patients, long-term aneurysmal dilatation of the false lumen (FL) is considered virtually inevitable and is associated with poorer disease outcomes. While the pathophysiological mechanisms driving FL dilatation are not yet understood, hemodynamic factors are believed to play a key role. Computational Fluid Dynamics (CFD) and 4D-Flow MRI (4DMR) analyses have revealed correlations between flow helicity, oscillatory wall shear stress, and aneurysmal dilatation of the FL. In this study, we compare CFD simulations using a patient-specific, three-dimensional, three-component inlet velocity profile (3D IVP) extracted from 4DMR data against simulations with flow rate-matched uniform and axial velocity profiles that remain widely used in the absence of 4DMR. We also evaluate the influence of measurement errors in 4DMR data by scaling the 3D IVP to the degree of imaging error detected in prior studies. We observe that oscillatory shear and helicity are highly sensitive to inlet velocity distribution and flow volume throughout the FL and conclude that the choice of IVP may greatly affect the future clinical value of simulations.
Distinct transcriptomic profile of satellite cells contributes to preservation of neuromuscular junctions in extraocular muscles of ALS mice
Authors: Li Ang , Yi Jianxun , Li Xuejun , Dong Li , Ostrow Lyle W. , Ma Jianjie , Zhou Jingsong
Published: February 2023

Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disorder characterized by progressive weakness of almost all skeletal muscles, whereas extraocular muscles (EOMs) are comparatively spared. While hindlimb and diaphragm muscles of end-stage SOD1G93A (G93A) mice (a familial ALS mouse model) exhibit severe denervation and depletion of Pax7+satellite cells (SCs), we found that the pool of SCs and the integrity of neuromuscular junctions (NMJs) are maintained in EOMs. In cell sorting profiles, SCs derived from hindlimb and diaphragm muscles of G93A mice exhibit denervation-related activation, whereas SCs from EOMs of G93A mice display spontaneous (non-denervation-related) activation, similar to SCs from wild-type mice. Specifically, cultured EOM SCs contain more abundant transcripts of axon guidance molecules, includingCxcl12, along with more sustainable renewability than the diaphragm and hindlimb counterparts under differentiation pressure. In neuromuscular co-culture assays, AAV-delivery ofCxcl12to G93A-hindlimb SC-derived myotubes enhances motor neuron axon extension and innervation, recapitulating the innervation capacity of EOM SC-derived myotubes. G93A mice fed with sodium butyrate (NaBu) supplementation exhibited less NMJ loss in hindlimb and diaphragm muscles. Additionally, SCs derived from G93A hindlimb and diaphragm muscles displayed elevated expression ofCxcl12and improved renewability following NaBu treatmentin vitro. Thus, the NaBu-induced transcriptomic changes resembling the patterns of EOM SCs may contribute to the beneficial effects observed in G93A mice. More broadly, the distinct transcriptomic profile of EOM SCs may offer novel therapeutic targets to slow progressive neuromuscular functional decay in ALS and provide possible "response biomarkers" in pre-clinical and clinical studies.