bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying and Acknowledging a Sex Gap in Lower-Limb Prosthetics Research: A Review
Authors: Ljung Jonas , Iacangelo Abigail
Published: April 2023

Introduction

Sex bias in research and treatment is a known phenomenon in medicine. This review seeks to identify and highlight the disparity in sex or gender representation in lower-limb prosthetic research, as well as examine what types of studies are less likely to exclude females.

Methods

The electronic databases of Journal of Prosthetics and Orthotics and Prosthetics and Orthotics International were reviewed for lower-limb prosthetic literature to determine how frequently sex is considered when conducting research on the fit and function of a device over the last 5 years. Metadata about various study characteristics was copied and analyzed for patterns.

Results

A total of 191 manuscripts were analyzed in this review. All together, the studies included 25.4% of female participants, which is below the approximate 34.6% female individuals living with amputation. No apparent difference in recruitment was noted between the sample size of the study, and a 32.9% increase of female representation was seen over the time frame of the study.

Conclusions

Although a positive increase in female participants over time was identified, a significant disparity in male and female research subjects is still prevalent throughout prosthetic research. In particular, high-validity study types such as randomized control trials and systematic reviews both fell well short of the approximate number of females with amputations. Studies that were analyzing prosthetic components and developing troubleshooting/diagnostic techniques were also well below the necessary female participants, likely contributing to poor fitting outcomes.

Clinical Relevance

Although evidence-based care aims to integrate research with clinical expertise with the ideal of providing the most appropriate treatment for the patient, this article demonstrates that a third of the population of persons living with amputation are rarely included in research trials. This article can be used as a tool for clinicians in deciding when the research should and should not be considered for a particular patient.
Timely surgical fixation confers beneficial outcomes in patients’ concomitant flail chest with mild-to-moderate traumatic brain injury: a trauma quality improvement project analysis – a cohort study
Authors: Liao Chien-An , Kuo Ling-Wei , Huang Jen-Fu , Fu Chih-Yuan , Chen Szu-An , Tee Yu-San , Hsieh Chi-Hsun , Liao Chien-Hung , Cheng Chi-Tung , Young Tai-Horng , Hsu Chih-Po
Published: April 2023

Background:

Traumatic flail chest results in respiratory distress and prolonged hospital stay. Timely surgical fixation of the flail chest reduces respiratory complications, decreases ventilator dependence, and shortens hospital stays. Concomitant head injury is not unusual in these patients and can postpone surgical timing due to the need to monitor the status of intracranial injuries. Reducing pulmonary sequelae also assists in the recovery from traumatic brain injury and improves outcomes. No previous evidence supports that early rib fixation can improve the outcome of patients with concomitant flail chest and traumatic brain injury.

Research Question:

Can early rib fixation improve the outcome of patients with concomitant flail chest and traumatic brain injury?

Study Design and Methods:

Adult patients with blunt injuries from the Trauma Quality Improvement Project between 2017 and 2019 were eligible for inclusion. Patients were divided into two treatment groups: operative and nonoperative. Inverse probability treatment weighting was used to identify the predictors of mortality and adverse hospital events.

Results:

Patients in the operative group had a higher intubation rate [odds ratio (OR), 2.336; 95% CI, 1.644–3.318; p<0.001), a longer length of stay (coefficient β, 4.664; SE, 0.789; p<0.001), longer ventilator days (coefficient β, 2.020; SE, 0.528; p<0.001), and lower mortality rate (OR], 0.247; 95% CI, 0.135–0.454; p<0.001).

Interpretation:

Timely rib fixation can improve the mortality rate of patients with flail chest and a concomitant mild-to-moderate head injury.
Collaborating With Community Partners to Address Population Health in an Online Advanced Nursing Practice Course
Authors: Watts Theresa , Green Jordyn E.
Published: April 2023

Background:

Engaging in effective community partnerships is a core competency for advanced nursing practice.

Purpose:

To describe a semester-long population health project that involved collaboration with a community partner in an online and asynchronous advanced nursing practice course and to evaluate students' perceptions of their community partner collaboration.

Methods:

At the beginning of the course, students selected health topics and community partners. Perceptions of the collaboration were evaluated in a survey. Data were analyzed using descriptive statistics and content analysis.

Results:

Approximately 59% of the students found the community partnership was very valuable. Barriers for working with community partners included reluctancy, feeling like a burden, and challenges with scheduling. Facilitators for working with community partners included receiving support on the project, gaining new perspectives, and the collaborative relationship.

Conclusions:

Community partnership assignments on population health projects can support students in obtaining skills on effective community partnerships while they are in their education programs.
The Utility of Biomarkers in the Clinical Management of Syphilis: A Systematic Review
Authors: Lorenz Zachary W. , Nijhar Sukhjeevan , Caufield-Noll Christine , Ghanem Khalil G. , Hamill Matthew M.
Published: April 2023

Background

Routinely available laboratory tests for Treponema pallidum remain suboptimal for diagnostic, prognostic, predictive, and monitoring purposes. Biomarkers with enhanced performance characteristics can improve diagnostic confidence and facilitate management. We conducted a systematic review to examine the utility of biomarkers in the diagnosis and management of syphilis.

Methods

We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses to identify articles for inclusion and independently reviewed them for eligibility and study quality using a 3-stage procedure. The search, conducted by a senior library informationist, used PubMed, Embase, Cochrane Library, and Scopus and included any study published before May 2022.

Results

Of the 111 studies identified, 31 (27.9%) were included in our review. Most studies were cross-sectional or prospective. The data were strikingly heterogeneous examining a variety of biomarkers across different syphilis stages, using different methodologies and definitions of treatment success. Available publications chiefly focused on diagnosing various syphilis stages, neurosyphilis and congenital syphilis, serological cure, the serofast state, and reinfection.

Conclusions

Despite increasing attempts to identify novel biomarkers, we found limited evidence to support the use of any biomarker in clinical decision making at this time; the syphilis biomarker literature is heterogenous and lacks measurement of clinically meaningful end points. We recommend the formation of a working group to set priorities for syphilis biomarker research and to guide future study of clinically meaningful biomarkers.
Routine Photography of Injuries
Authors: Giorgetti Arianna , Pascali Jennifer Paola , Pelletti Guido , Silvestri Annamaria , Giovannini Elena , Pelotti Susi , Fais Paolo
Published: April 2023

Ten lesions were photographed with an entry-level (HUAWEI P smart 2019), a midrange (Samsung Galaxy S8) and a high range (Apple Iphone XR) smartphone camera and with a digital single-lens camera (DSLC). Images were independently rated by 3 pathologists, based on comparison to the real lesion and “visual impact.” Difference of perceptual lightness coordinates between smartphones and the criterion standard (DSLC) was calculated.

The highest ranking for adherence to reality was obtained with DSLC, while the highest ranking for visual impact was obtained with the Iphone. The color representation better reflecting the criterion standard (DSLC) was obtained for the entry-level smartphone.

All the devices allow to assess the general features (ie, the color, the shape, and the main characteristics) of an injury during a forensic autopsy. However, results might be different when photos are obtained in suboptimal, such as low-light, conditions. Moreover, images acquired through a smartphone camera might be unsuitable for later image exploitation, such as enlargement of a portion of the image to magnification of a detail, which seemed not relevant when the photo was shot. Only a raw image, acquired using a dedicated camera and deactivating images manipulation software, might allow the preservation of the true data.
“Separating Myth from Reality in Breast Implants: An Overview of 30 years of Experience”
Authors: McGuire Patricia A , Glicksman Caroline , McCarthy Colleen , Spiegel Aldona
Published: April 2023

The purpose of this special topic paper is to review the pivotal events in the history of breast implants in the United States, from the events leading to the FDA Moratorium on the use of silicone gel implants and subsequent approval, the emergence of breast implant associated anaplastic large cell lymphoma, and persistent concerns about an association between breast implants, autoimmune disease, and systemic symptoms. This paper reviews the medical literature to outline our current knowledge on BIA-ALCL with recommendations for diagnosis and management of symptomatic and asymptomatic patients with textured implants and the science of potential associations of implants to autoimmune and systemic symptoms so that we can help our patients separate myths from reality and make educated decisions on having breast implants placed or removed.
Clinical Practice Patterns and Evidence-Based Medicine in Abdominoplasty: 16-Year Analysis of Continuous Certification Tracer Data from the American Board of Plastic Surgery
Authors: Stein Michael J. , Weissman Joshua P. , Harrast John , Rubin J. Peter , Gosain Arun K. , Matarasso Alan
Published: April 2023

Introduction:

This study evaluates trends in practice patterns for abdominoplasty based on a 16-year review of tracer data collected by the American Board of Plastic Surgery (ABPS) as part of the Continuous Certification (CC) process.

Methods:

In order to facilitate comparison of an equal number of patients over time, tracer data from 2005 to 2021 was split into an “early cohort (EC)” from 2005-2014 and a “recent cohort (RC)” from 2015-2021. Fisher’s exact tests and two-sample t-tests compared patient demographics, surgical techniques, and complication rates.

Results:

Data from 8990 abdominoplasties (4740 EC, 4250 RC) was analyzed. Recent cohort abdominoplasties report a lower rate of complications (19% compared to 22% for EC, p<0.001) and a lower rate of revisionary surgery (8% compared to 10% for EC, p<0.001). This has occurred despite the increased use of abdominal flap liposuction (25% vs 18% for EC, p<0.001). Wide undermining, (81% vs 75%, p<0.001), vertical plication (89% vs 86%, p<0.001), and the use of surgical drains (93% vs 89%, p<0.001) have all been reduced to a significant degree in the RC. Abdominoplasty surgery is increasingly performed in an outpatient setting, with increased use of chemoprophylaxis for thrombosis prevention.

Conclusions:

Analysis of this ABPS tracer data highlights important trends in clinical practice over the last 16 years. Abdominoplasty continues to be a safe and effective procedure with similar complication and revision rates over the 16-year cohort.
Intraductal Carcinoma: The Carcinoma In Situ of the Salivary Gland
Authors: Thomas Rhema , Umar Tijjani , Borumandi Farzad
Published: April 2023

Intraductal carcinoma of the salivary gland (IDC) is a rare in situ neoplasm of the salivary gland with similar features to the ductal carcinoma in situ of the breast. This report aims to present the clinical presentation and histological features of IDC. The authors present a 90-year-old gentleman with an indurated and painless tumor within the right parotid. Preoperative diagnostics, including fine needle aspiration cytology, ultrasound scan, and magnetic resonance imaging, were suggestive of Warthin tumor. The patient is disease free within the follow-up period of 33 months. Intraductal carcinoma is an indolent phenotype with only a few reported cases with nodal metastases, and to the best of our knowledge, no cases have been reported with distant metastases. Complete surgical excision is recommended to prevent a recurrence. The knowledge of this underreported salivary gland malignancy is important to prevent misdiagnosis and insufficient treatment.
Application of Simplified Duct-to-Mucosa Pancreaticojejunostomy for Nondilated Pancreatic Duct in Laparoscopic Pancreatic Surgery
Authors: Zhou Haihua , Wu Xiaokang
Published: April 2023

Objective:

The objective of this study was to investigate the feasibility of simplified duct-to-mucosa pancreaticojejunostomy in a nondilated pancreatic duct in laparoscopic surgery.

Materials and Methods:

The data of 19 patients who underwent laparoscopic pancreaticoduodenectomy (LPD) and 2 patients who underwent laparoscopic central pancreatectomy were retrospectively analyzed.

Results:

All patients underwent pure laparoscopic surgery successfully with simplified duct-to-mucosa pancreaticojejunostomy. The operation time of LPD was 365.11±41.56 minutes, the time of pancreaticojejunostomy was 28.39±12.58 minutes, and postoperative hospitalization time was 14.16±6.88 days on average. Postoperative complications occurred in 3 patients of LPD, including 2 cases of class B postoperative pancreatic fistula and 1 case of gastroparesis followed by gastrointestinal anastomotic perforation. The operative time of laparoscopic central pancreatectomy was 191.00±12.73 minutes, the time of pancreaticojejunostomy 36.00±5.66 minutes, and the postoperative hospitalization time 12.5±0.71 days on average.

Conclusions:

The described technique is a simple and safe reconstruction procedure and suitable for patients with nondilated pancreatic duct.
Codon pair bias deoptimization of essential genes in infectious laryngotracheitis virus reduces protein expression
Authors: Vaz Paola K. , Armat Marzieh , Hartley Carol A. , Devlin Joanne M.
Published: April 2023

Infectious laryngotracheitis virus (ILTV; an alphaherpesvirus) is a respiratory pathogen of chickens and causes significant economic losses in the poultry industry globally, in addition to severe animal health and welfare concerns. To date, studying the role of ILTV genes in viral infection, replication or pathogenesis has largely been limited to genes that can be deleted from the ILTV genome and the resultant deletion mutants characterized in vitro or in vivo. However, this approach is not suitable for the study of essential genes. This study trialled two different codon deoptimization techniques that aimed to separately disrupt and downregulate the expression of two ILTV genes, ICP8 and UL12, which are essential or very important in viral replication. The target genes were partially recoded using codon usage deoptimization (CUD) and codon pair bias deoptimization (CPBD) approaches and characterized in vitro. Viruses deoptimized via CPBD showed decreased protein expression as assessed by Western blotting and/or fluorescence microscopy to measure the intensity of the fluorescent marker fused to the target protein. Viruses deoptimized by CUD showed less consistent results, with some mutants that could not be generated or isolated. The results indicate that CPBD is an attractive and viable tool for the study of essential or critically important genes in ILTV. This is the first study, to our knowledge, that utilizes CPBD and CUD techniques for the study of ILTV genes.
Decoding the Best Automated Segmentation Tools for Vascular White Matter Hyperintensities in the Aging Brain: A Clinician’s Guide to Precision and Purpose
Authors: Torres-Simon Lucia , del Cerro-León Alberto , Yus Miguel , Bruña Ricardo , Gil-Martinez Lidia , Marcos Dolado Alberto , Maestú Fernando , Arrazola-Garcia Juan , Cuesta Pablo
Published: April 2023

Cerebrovascular damage from small vessel disease (SVD) occurs in healthy and pathological aging. SVD markers, such as white matter hyperintensities (WMH), are commonly found in individuals over 60 and increase in prevalence with age. WMHs are detectable on standard MRI by adhering to the STRIVE criteria. Currently, visual assessment scales are used in clinical and research scenarios but is time-consuming and has rater variability, limiting its practicality. Addressing this issue, our study aimed to determine the most precise WMH segmentation software, offering insights into methodology and usability to balance clinical precision with practical application. This study employed a dataset comprising T1, FLAIR, and DWI images from 300 cognitively healthy older adults. WMHs in this cohort were evaluated using four automated neuroimaging tools: Lesion Prediction Algorithm (LPA) and Lesion Growth Algorithm (LGA) from Lesion Segmentation Tool (LST), Sequence Adaptive Multimodal Segmentation (SAMSEG), and Brain Intensity Abnormalities Classification Algorithm (BIANCA). Additionally, clinicians manually segmented WMHs in a subsample of 45 participants to establish a gold standard. The study assessed correlations with the Fazekas scale, algorithm performance, and the influence of WMH volume on reliability. Results indicated that supervised algorithms were superior, particularly in detecting small WMHs, and can improve their consistency when used in parallel with unsupervised tools. The research also proposed a biomarker for moderate vascular damage, derived from the top 95th percentile of WMH volume in healthy individuals aged 50 to 60. This biomarker effectively differentiated subgroups within the cohort, correlating with variations in brain structure and behavior.
Exploring approaches to weighting estimates of facility readiness to provide health services used for estimating input-adjusted effective coverage: a case study using data from Tanzania
Authors: Sheffel Ashley , Carter Emily , Niyeha Debora , Yahya-Malima Khadija I. , Malamsha Deogratius , Shagihilu Shagihilu , Munos Melinda
Published: April 2023

The ideal approach for calculating effective coverage of health services using ecological linking requires accounting for variability in facility readiness to provide health services and patient volume by incorporating adjustments for facility type into estimates of facility readiness and weighting facility readiness estimates by service-specific caseload. The aim of this study is to compare the ideal caseload-weighted facility readiness approach to two alternative approaches 1) facility-weighted readiness and 2) observation-weighted readiness to assess the suitability of each as a proxy for caseload-weighted facility readiness. We utilized the 2014-2015 Tanzania Service Provision Assessment along with routine health information system data to calculate facility readiness estimates using the three approaches. We then conducted equivalence testing, using the caseload-weighted estimates as the ideal approach and comparing with the facility-weighted estimates and observation-weighted estimates to test for equivalence. Comparing the facility-weighted readiness estimates to the caseload-weighted readiness estimates, we found 58% of estimates met the requirements for equivalence. In addition, the facility-weighted readiness estimates consistently underestimated, by a small percentage, facility readiness as compared to the caseload-weighted readiness estimates. Comparing the observation-weighted readiness estimates to the caseload-weighted readiness estimates, we found 64% of estimates met the requirements for equivalence. We found that, in this setting, both facility-weighted readiness and observation-weighted readiness may be reasonable proxies for caseload-weighted readiness. However, in a setting with more variability in facility readiness or larger differences in facility readiness between low caseload and high caseload facilities, the observation-weighted approach would be a better option than the facility-weighted approach. While the methods compared showed equivalence, our results suggest that selecting the best method for weighting readiness estimates will require assessing data availability alongside knowledge of the country context.
Single-cell time-resolved multi-omics reveal apoptotic and ferroptotic heterogeneity during foam cell formation
Authors: Wang Yiwen , Lin Ling , Qiao Liang
Published: April 2023

Macrophage-derived foam cell plays a pivotal role in the plaque formation and rupture during the progression of atherosclerosis. Foam cells are destined to divergent cell fate and functions in response to external stimuli based on their internal states, which however is hidden in the traditional studies based on population of cells. Herein, we used time-resolved and single-cell multi-omics to investigate the macrophage heterogeneity along foam cell formation. Dynamic metabolome and lipidome outlined the dual regulating axis of inflammation and ferroptosis. Single cell metabolomics and lipidomics further demonstrated a macrophage continuum featuring a differed susceptibility to apoptosis and ferroptosis. Using single-cell transcriptomic profiling, we verified the divergent cell fate toward apoptosis or ferroptosis. Therefore, the molecular choreography underlying the divergent cell fate during foam cell formation was revealed, which is of high significance for the understanding of the pathogenesis of atherosclerosis and development of new drug targets.
RAVEN: development of a novel volumetric extrusion-based system for small-scale Additive Manufacturing
Authors: Fucile Pierpaolo , David Vivek Cherian , Kalogeropoulou Maria , Gloria Antonio , Moroni Lorenzo
Published: April 2023

Recent technological advances in the field of Additive Manufacturing (AM) and the increasing need in Regenerative Medicine (RM) for devices that better and better mimic native tissues architecture are showing limitations in the current scaffolds fabrication techniques. A switch from the typical layer-by-layer approach is needed to achieve precise control on fibers orientation and pores dimension and morphology. In this work a new AM apparatus, the RAVEN (Robot-Assisted Volumetric ExtrusioN) system, is presented. RAVEN is based on a 7-DOF robotic arm and an FDM extruder and allows for volumetric extrusion of polymeric filaments. The development process, namely the robotic motion optimization, the optimization towards small-scale trajectories, the custom-made hardware/software interfaces, and the different printing capabilities are hereby presented. The successful results are promising towards future advanced applications such asin vivobioprinting, in which the ability of the robot to change its configuration while printing will be crucial.
Dietary calcium (Ca2+) impacts Ca2+content and molecular expression of Ca2+-transporters in Malpighian tubules of the yellow fever mosquito,Aedes aegypti
Authors: Li Yuan , Piermarini Peter M.
Published: April 2023

The renal (Malpighian) tubules of insects play important roles in hemolymph Ca2+regulation. Here we provide the first investigation into how dietary Ca2+loads from sucrose or blood meals affect the Ca2+content and mRNA expression of Ca2+transporters in Malpighian tubules of adult female mosquitoes. Using the yellow fever mosquitoAedes aegyptiwe found that feeding females for 6 daysad libitumon 10% sucrose with elevated Ca2+concentration led to concentration-dependent increases of the Ca2+content in Malpighian tubules. The increases of Ca2+content correlated with up-regulations of mRNAs encoding intracellular Ca2+-ATPases (SERCAandSPCA), a plasma membrane Ca2+-ATPase (PMCA), and a K+-dependent Na+/Ca2+exchanger (NCKX1). We also found that when adult females were fed blood, tubule Ca2+content changed dynamically over the next 72 h in a manner consistent with redistribution of tubule Ca2+stores to other tissues (e.g., ovaries). The changes in tubule Ca2+were correlated with dynamic changes in mRNA abundances ofSERCA,SPCA,PMCA, andNCKX1. Our results are the first to demonstrate that Malpighian tubules of adult female mosquitoes have a remarkable capacity to handle high dietary Ca2+loads, most likely through the combination of storing excess Ca2+within intracellular compartments and secreting it into the tubule lumen for excretion. Our results also suggest that the Malpighian tubules play key roles in supplying Ca2+to other tissues during the processing of blood meals.
Magnetically Controlled Cyclic Microscale Deformation ofIn VitroCancer Invasion Models
Authors: Asgeirsson D.O. , Mehta A. , Hesse N. , Scheeder A. , Ward R. , Li F. , Christiansen M. G. , De Micheli A. J. , Ildic E. S. , Aceto N. , Schuerle S.
Published: April 2023

Mechanical cues play an important role in the metastatic cascade of cancer. Three-dimensional (3D) tissue matrices with tunable stiffness have been extensively used as model systems of the tumor microenvironment for physiologically relevant studies. Tumor-associated cells actively deform these matrices, providing mechanical cues to other cancer cells residing in the tissue. Mimicking such dynamic deformation in the surrounding tumor matrix may help clarify the effect of local strain on cancer cell invasion. Remotely controlled microscale magnetic actuation of such 3Din vitrosystems is a promising approach, offering a non-invasive means for in situ interrogation. Here, we investigate the influence of cyclic deformation on tumor spheroids embedded in matrices, continuously exerted for days by cell-sized anisotropic magnetic probes, referred to as µRods. Particle velocimetry analysis revealed the spatial extent of matrix deformation produced in response to a magnetic field, which was found to be on the order of 200 µm, resembling strain fields reported to originate from contracting cells. Intracellular calcium influx was observed in response to cyclic actuation, as well as an influence on cancer cell invasion from 3D spheroids, as compared to unactuated controls. Localized actuation at one side of a tumor spheroid tended to result in anisotropic invasion toward the µRods causing the deformation. In summary, our approach offers a strategy to test and control the influence of non-invasive micromechanical cues on cancer cell invasion and metastasis.
Predicting bipolar disorder incidence in young adults using gradient boosting: a 5-year follow-up study
Authors: Montezano Bruno Braga , Gnielka Vanessa , Shintani Augusto Ossamu , de Aguiar Kyara Rodrigues , Roza Thiago Henrique , de Azevedo Cardoso Taiane , de Mattos Souza Luciano Dias , Moreira Fernanda Pedrotti , da Silva Ricardo Azevedo , Mondin Thaíse Campos , Jansen Karen , Passos Ives Cavalcante
Published: April 2023

This study aimed to develop a classification model predicting incident bipolar disorder (BD) cases in young adults within a 5-year interval, using sociodemographic and clinical features from a large cohort study. We analyzed 1,091 individuals without BD, aged 18 to 24 years at baseline, and used the XGBoost algorithm with feature selection and oversampling methods. Forty-nine individuals (4.49%) received a BD diagnosis five years later. The best model had an acceptable performance (test AUC: 0.786, 95% CI: 0.686, 0.887) and included ten features: feeling of worthlessness, sadness, current depressive episode, selfreported stress, self-confidence, lifetime cocaine use, socioeconomic status, sex frequency, romantic relationship, and tachylalia. We performed a permutation test with 10,000 permutations that showed the AUC from the built model is significantly better than random classifiers. The results provide insights into BD as a latent phenomenon, as depression is its typical initial manifestation. Future studies could monitor subjects during other developmental stages and investigate risk populations to improve BD characterization. Furthermore, the usage of digital health data, biological, and neuropsychological information and also neuroimaging can help in the rise of new predictive models.
Is there a bilingual advantage in auditory attention among children? A systematic review and meta-analysis of standardized auditory attention tests
Authors: Bao Wenfu , Alain Claude , Thaut Michael , Molnar Monika
Published: April 2023

A wealth of research has investigated the effects of bilingualism on cognition, especially on executive function. Developmental studies reveal different cognitive profiles between monolinguals and bilinguals in (audio-)visual attention tasks, which might stem from their attention allocation differences. Yet, whether such distinction exists in the auditory domain alone is unknown. In this study, we compared differences in auditory attention, measured by standardized tests, between monolingual and bilingual children. A comprehensive literature search was conducted in three electronic databases: OVID Medline, OVID PsycInfo, and EBSCO CINAHL. Twenty studies using standardized tests to assess auditory attention in monolingual and bilingual participants aged less than 18 years were identified. We assessed the quality of these studies using a scoring tool for evaluating primary research. For statistical analysis, we pooled the effect size in a random-effects meta-analytic model, where between-study heterogeneity was quantified using theI2statistic. No substantial publication bias was observed based on the funnel plot. Further, meta-regression modelling suggests that test measure (accuracy vs. response times) significantly affected the studies’ effect sizes whereas other factors (e.g., participant age, stimulus type) did not. Specifically, studies reporting accuracy observed marginally greater accuracy in bilinguals (g= 0.10), whereas those reporting response times indicated faster latency in monolinguals (g= -0.34). There was little difference between monolingual and bilingual children’s performance on standardized auditory attention tests. We also found that studies tend to include a wide variety of bilingual children but report limited language background information of the participants. This, unfortunately, limits the potential theoretical contributions of the reviewed studies. Recommendations to improve the quality of future research are discussed.
A nationwide multistate analysis estimating the rates and risks of transferring critically ill COVID-19 patients during the Delta and Omicron waves in Germany
Authors: Lottes Matthäus , Grodd Marlon , Grabenhenrich Linus , Wolkewitz Martin
Published: April 2023

Background

The spread of several SARS-CoV-2 variants of concern (VOC) led to increasing numbers of patients with coronavirus disease 2019 (COVID-19) in German intensive care units (ICU), resulting in capacity shortages and even transfers of COVID-19 ICU patients between federal states in late 2021. Comprehensive evidence on the impact of predominant VOC, in this case Delta and Omicron, on inter-hospital transfers of COVID-19 ICU patients remains scarce.

Methods

A retrospective cohort study was conducted from July 01, 2021 until May 31, 2022 using nationwide reimbursement inpatient count data of COVID-19 ICU patients and weekly sequence data of VOC in Germany. A multivariable Poisson regression analysis was performed to estimate incidence rates and incidence rate ratios (IRR) for competing events of transfer, discharge and death, adjusted for VOC infection, age group and sex. For corresponding risk estimation, a multistate model for the clinical trajectory in ICU was applied.

Results

Omicron versus Delta infection yielded estimated adjusted IRR of 1.23 (95% CI, 1.16 – 1.30) for transfer, 2.27 (95% CI, 2.20 – 2.34), for discharge and 0.98 (95% CI, 0.94 – 1.02) for death. For death in ICU, estimated adjusted IRR increased progressively with age up to 4.09 (95% CI, 3.74 – 4.47) for those 90 years and older. COVID-19 ICU patients with Omicron infection were at comparatively higher estimated risk of discharge, whereas the estimated risk of transfer and death were higher for those with Delta infection.

Conclusions

Inter-hospital transfers and discharges occurred more frequently in COVID-19 ICU patients with Omicron infection than in those with Delta infection, who in turn had a higher estimated risk of death. Age emerges as a relevant determinant for fatal clinical trajectories in COVID-19 ICU patients and imposes close therapeutic care.
The Impact Of Alcohol Minimum Unit Pricing On People with experience of Homelessness: Qualitative Study
Authors: Emslie Carol , Dimova Elena , O’Brien Rosaleen , Whiteford Martin , Johnsen Sarah , Rush Robert , Smith Iain D. , Stockwell Tim , Whittaker Anne , Elliott Lawrie
Published: April 2023

BACKGROUND

Alcohol Minimum Unit Pricing (MUP) was introduced in Scotland in May 2018. Existing evidence suggests MUP can reduce alcohol consumption in the general population, but there is little research about its impact on vulnerable groups. This qualitative study aimed to explore experiences of MUP among people with experience of homelessness.

METHODS

We conducted qualitative semi-structured interviews with a purposive sample of 46 people with current or recent experience of homelessness who were current drinkers when MUP was introduced. Participants (30 men and 16 women) were aged 21 to 73 years. Interviews focused on views and experiences of MUP. Data were analysed using thematic analysis.

RESULTS

People with experience of homelessness were aware of MUP but it was accorded low priority in their hierarchy of concerns. Reported impacts varied. Some participants reduced their drinking, or moved away from drinking strong white cider in line with policy intentions. Others were unaffected because the cost of their preferred drink (usually wine, vodka or beer) did not change substantially. A minority reported increased involvement in begging. Wider personal, relational and social factors also played an important role in participant responses to MUP.

CONCLUSION

Our findings suggest that MUP worked as intended for some people with experience of homelessness, while a minority reported negative consequences. Our findings highlight the importance of considering the impact of population level health policies on marginalised groups. Policymakers in Scotland, and elsewhere, need to consider wider contextual factors that affect responses to MUP in people with experience of homelessness. It is important to invest further in secure housing and appropriate support services for people with experience of homelessness who consume alcohol, and implement and evaluate harm reduction initiatives such as managed alcohol programmes.
Toxoplasma gondiiinfection alters the recognition response of dendritic cells to stiffness substrate
Authors: Sun ZhePeng , Liu Jing , Zhu ZiFu , Ying Zhu , Zhou ZiHui , Liu Qun
Published: April 2023

Toxoplasma gondii(T.gondii) hijacks host immune cells as ‘Trojan Horse’, and the infected cells accelerated the parasites dissemination. During acute infection,T.gondiispecificity crosses the blood-brain-barrier to enter the brain. This selective mode of parasite transmission may be associated with the directed migration of infected immune cells. Immune cells follow various environmental cues for directional migration. However, the effect ofT.gondiiinfection on the recognition of mechanical cues by immune cells remains unknown. Here, we examined the adhesion and migration ofT.gondii-infected dendritic cells (DCs) on high and low stiffness substrates. We found thatT.gondiiinfection alters the durotaxis migration of DCs. Infected DC exhibited stronger adhesion and lower migration on low stiffness substrates. In contrast to uninfected DCs, infected DCs migrated towards the low stiffness environment. TgWIP and TgROP17 co-regulate the F-actin structure of DCs and are involved in the formation of abnormal F-actin filaments. Rearrangement of the F-actin structure resulting fromT.gondiiinfection regulates DCs’ abnormal recognition response to the mechanical cues. Recognition of DCs to the mechanical signals is independent of β2- integrin expression. Meanwhile, challenging DCs withT.gondiiincreased the phosphorylation of focal adhesion kinase (FAK). Treatment with a FAK inhibitor (VS- 6063) influences the recognition response of infected DCs. FAK inhibition in adoptively transferred infected DCs effectively prevents the dissemination ofT.gondiito the brain. The data reveal thatT.gondiiinfection inversely affects the durotaxis of DCs by altering the phosphorylation level of FAK and remodeling of F-actin structure.T.gondiiutilizes the change in DCs’ durotaxis migration to accelerate the parasites crossing the blood-brain-barrier.

Author Summary

Immune cells travel through blood vessels and lymph vessels to various tissues, and respond to different types of environmental cues. Cells sense the cues and transmit these information to the cytoskeletal which induce directed cell migration towards or away from these signals.T.gondiiinfection remodeling the cytoskeletal of DCs which may cause abnormalities in these cues transduction. We found thatT.gondiiinfection induces the formation of abnormal F-actin filaments in DCs, TgWIP and TgROP17 co-regulate the DCs’ F-actin structure.T.gondiiinfection increased the phosphorylation of FAK in DCs and has no effect with DCs surface β2-integrin expression. These reasons lead to alter the original durotaxis migration of DCs, and makes infected-DCs tend to stay in the low stiffness environment. Meanwhile, the recognition response of infected DC to mechanical signal determines the parasite rapid crossing the blood-brain-barrier.
Genetic impacts on DNA methylation help elucidate regulatory genomic processes
Authors: Villicaña Sergio , Castillo-Fernandez Juan , Hannon Eilis , Christiansen Colette , Tsai Pei-Chien , Maddock Jane , Kuh Diana , Suderman Matthew , Power Christine , Relton Caroline , Ploubidis George , Wong Andrew , Hardy Rebecca , Goodman Alissa , Ong Ken K. , Bell Jordana T.
Published: April 2023

Pinpointing genetic impacts on DNA methylation can improve our understanding of pathways that underlie gene regulation and disease risk. We report heritability and methylation quantitative trait locus (meQTL) analysis at 724,499 CpGs profiled with the Illumina Infinium MethylationEPIC array in 2,358 blood samples from three UK cohorts, with replication. Methylation levels at 34.2% of CpGs were affected by SNPs, and 98% of effects werecis-acting or within 1 Mbp of the tested CpG. Our results are consistent with meQTL analyses based on the former Illumina Infinium HumanMethylation450 array. Both meQTL SNPs and CpGs with meQTLs were overrepresented in enhancers, which have improved coverage on this platform compared to previous approaches. Co-localisation analyses across genetic effects on DNA methylation and 56 human traits identified 1,520 co-localisations across 1,325 unique CpGs and 34 phenotypes, including in disease-relevant genes, suchICOSLG(inflammatory bowel disease), andUSP1andDOCK7(total cholesterol levels). Enrichment analysis of meQTLs and integration with expression QTLs gave insights into mechanisms underlyingcis-meQTLs, for example through disruption of transcription factor binding sites for CTCF and SMC3, andtrans-meQTLs, for example through regulating the expression ofACDandSENP7which can modulate DNA methylation at distal sites. Our findings improve the characterisation of the mechanisms underlying DNA methylation variability and are informative for prioritisation of GWAS variants for functional follow-ups. A results database and viewer are available online.
Dynamic molecular mechanism of the nuclear pore complex permeability barrier
Authors: Kozai Toshiya , Fernandez-Martinez Javier , van Eeuwen Trevor , Gallardo Paola , Kapinos Larisa E. , Mazur Adam , Zhang Wenzhu , Tempkin Jeremy , Panatala Radhakrishnan , Delgado-Izquierdo Maria , Raveh Barak , Sali Andrej , Chait Brian T. , Veenhoff Liesbeth M. , Rout Michael P. , Lim Roderick Y. H.
Published: April 2023

Nuclear pore complexes (NPCs) mediate nucleocytoplasmic transport of specific macromolecules while impeding the exchange of unsolicited material. However, key aspects of this gating mechanism remain controversial. To address this issue, we determined the nanoscopic behavior of the permeability barrier directly within yeastS. cerevisiaeNPCs at transport-relevant timescales. We show that the large intrinsically disordered domains of phenylalanine-glycine repeat nucleoporins (FG Nups) exhibit highly dynamic fluctuations to create transient voids in the permeability barrier that continuously shape-shift and reseal, resembling a radial polymer brush. Together with cargo-carrying transport factors the FG domains form a feature called the central plug, which is also highly dynamic. Remarkably, NPC mutants with longer FG domains show interweaving meshwork-like behavior that attenuates nucleocytoplasmic transportin vivo. Importantly, thebona fidenanoscale NPC behaviors and morphologies are not recapitulated byin vitroFG domain hydrogels. NPCs also exclude self-assembling FG domain condensatesin vivo, thereby indicating that the permeability barrier is not generated by a self-assembling phase condensate, but rather is largely a polymer brush, organized by the NPC scaffold, whose dynamic gating selectivity is strongly enhanced by the presence of transport factors.
Heat-inactivated mycobacteria activate the Toll-like receptor 2 and 4 pathways in the zebrafish model of tuberculosis
Authors: Ferreras-Colino Elisa , Contreras Marinela , Risalde María A. , Sevilla Iker A. , Delgado Encarnación , Domínguez Lucas , Gortazar Christian , de la Fuente Jose
Published: April 2023

Based on previous evidence demonstrating the efficacy of inactivated mycobacteria for the control of fish mycobacteriosis, we explored the protective efficacy of two inactivatedMycobacterium bovisadministered via parenteral and mucosal routes againstMycobacterium marinuminfection mimicking natural conditions in the zebrafish model of tuberculosis. Although we did not observe a clear effect of any of the immunostimulants on mycobacterial burden, the results showed a significant increase in TLR2 and TLR4 gene expression levels in fishes parenterally immunized with inactivated Bacillus Calmette-Guérin (BCG). Our findings demonstrated that the TLR2 and the TLR4 signaling pathways are involved in the immune response elicited by inactivated mycobacteria in the zebrafish model of tuberculosis and support the use of inactivated mycobacteria in vaccine formulations for the control of mycobacteriosis.
Dominance is common in mammals and is associated with trans-acting gene expression and alternative splicing
Authors: Cui Leilei , Yang Bin , Xiao Shijun , Gao Jun , Baud Amelie , Graham Delyth , McBride Martin , Dominiczak Anna , Schafer Sebastian , Aumatell Regina Lopez , Mont Carme , Teruel Albert Fernandez , Hübner Norbert , Flint Jonathan , Mott Richard , Huang Lusheng
Published: April 2023

Background

Dominance and other non-additive genetic effects arise from the interaction between alleles, and historically these phenomena played a major role in quantitative genetics. However, today most genome-wide association studies (GWAS) assume alleles act additively.

Methods

We systematically investigated both dominance – here representing any non-additive effect - and additivity across 574 physiological and gene expression traits in three mammalian models: a Pig F2 Intercross, a Rat Heterogeneous Stock and a Mouse Heterogeneous Stock.

Results

In all species, and across all physiological traits, dominance accounts for about one quarter of the heritable variance. Hematological and immunological traits exhibit the highest dominance variance, possibly reflecting balancing selection in response to pathogens. Although most quantitative trait loci (QTLs) are detectable assuming additivity, we identified 154, 64 and 62 novel dominance QTLs in pigs, rats and mice respectively, that were undetectable as additive QTLs. Similarly, even though most cis-acting eQTLs are additive, we observed a large fraction of dominance variance in gene expression, and trans-acting eQTLs are enriched for dominance. Genes causal for dominance physiological QTLs are less likely to be physically linked to their QTLs but instead act via trans-acting dominance eQTLs. In addition, in HS rat transcriptomes, thousands of eQTLs associate with alternate transcripts and exhibit complex additive and dominant architectures, suggesting a mechanism for dominance.

Conclusions

Although heritability is predominantly additive, many mammalian genetic effects are dominant and likely arise through distinct mechanisms. It is therefore advantageous to consider both additive and dominance effects in GWAS to improve power and uncover causality.
Avoiding false discoveries: Revisiting an Alzheimer’s disease snRNA-Seq dataset
Authors: Murphy Alan E , Fancy Nurun Nahar , Skene Nathan G
Published: April 2023

Mathyset al., conducted the first single-nucleus RNA-Seq study (snRNA-Seq) of Alzheimer’s disease (AD)1. The authors profiled the transcriptomes of approximately 80,000 cells from the prefrontal cortex, collected from 48 individuals – 24 of which presented with varying degrees of AD pathology. With bulk RNA-Seq, changes in gene expression across cell types can be lost, potentially masking the differentially expressed genes (DEGs) across different cell types. Through the use of single-cell techniques, the authors benefitted from increased resolution with the potential to uncover cell type-specific DEGs in AD for the first time2. However, there were limitations in both their data processing and quality control and their differential expression analysis. Here, we correct these issues and use best-practice approaches to snRNA-Seq differential expression, resulting 549 times fewer differentially expressed genes at a false discovery rate (FDR) of 0.05.
Development and Validation of a Novel Instrument to Capture Companion Dog Mortality Data: The Dog Aging Project End of Life Survey
Authors: McNulty Kellyn E. , Creevy Kate E. , Fitzpatrick Annette , Wilkins Vanessa , Barnett Brian G. ,   DAP Consortium, Ruple Audrey
Published: April 2023

Objective

The researchers and clinicians within the Dog Aging Project (DAP), a longitudinal cohort study of aging in companion dogs, created and validated a novel survey instrument titled the End of Life Survey (EOLS) to gather owner-reported mortality data about companion dogs.

Sample

Bereaved dog owners who participated in the refinement, face validity assessment, or reliability assessment of the EOLS (n=42) and/or completed the entire survey between January 20 and March 24, 2021 (n=646).

Procedures

The EOLS was created and modified by veterinary health professionals and human gerontology experts using published literature, clinical veterinary experience, previously created DAP surveys, and feedback from a pilot study conducted with bereaved dog owners. The EOLS was subjected to qualitative validation methods and post-hoc free-text analysis to evaluate its ability to thoroughly capture scientifically relevant aspects of companion dogs’ death.

Results

The EOLS was well-received with excellent face validity as assessed by dog owners and experts. The EOLS had fair to substantial reliability for the three validation themes: cause of death (kappa = 0.73; 95% CI [0.5-0.95]), perimortem quality of life (kappa = 0.49; 95% CI [0.26-0.73]), and reason for euthanasia (kappa = 0.3; 95% CI [0.08-0.52]) and had no need for any substantial content alterations based on free-text analysis.

Clinical Relevance

The EOLS has proven to be a well-accepted, comprehensive, and valid instrument for capturing owner-reported companion dog mortality data and has the potential to enhance veterinarians’ ability to care for the aging dog population by illuminating their understanding of companion dogs’ end-of-life experiences.