bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of the NIOSH Worker Well-Being Questionnaire in Italian Language
Authors: Fontana Luca , Dolce Pasquale , Santocono Carolina , Annarumma Maddalena , Iavicoli Ivo
Published: March 2023

Objective

This study aimed to validate in Italian the Worker Well-Being Questionnaire developed by US National Institute for Occupational Safety and Health.

Methods

The questionnaire was independently translated into Italian by two authors. Translations were compared with obtain a synthesis that was back-translated. Back translations were submitted to an expert committee to produce a final version of the questionnaire. The Italian version, after being pretested, was administered guaranteeing anonymity to a total sample of 206 health care workers.

Results

Findings obtained are satisfactory, indicating excellent fit (CFI and TLI values ranged from 0.96 to 0.99, RMSEA values ranged from 0.03 to 0.07), sound internal consistency of scales (Cronbach’s α values exceeded 0.7) and factor structures consistent with theory.

Conclusions

Italian version of the questionnaire is faithful to the original and allows for efficient and robust measurement of workers’ well-being.
Incidence and Predictors of COVID-19 Infection in Prison Healthcare Workers
Authors: Caruth Julie , Black Kathleen , Legard Alicia , De Resende Adriana , Getz Kylie , Borowski Michelle , Debilio Lisa , Brewer Arthur , Kipen Howard , Udasin Iris G. , Graber Judith M.
Published: March 2023

Objective

The aim of the study is to assess the predictors of SARS-CoV-2 infection among correctional healthcare workers (HCWs).

Methods

We conducted a retrospective chart review to describe the demographic and workplace characteristics of New Jersey correctional HCWs between March 15, 2020, and August 31, 2020, using univariate and multivariable analysis.

Results

Among 822 HCWs, patient-facing staff had the highest incidence of infection (7.2%). Associated risk factors include being Black and working in a maximum-security prison. There were few statistically significant findings due to small total numbers (n = 47) that tested positive.

Conclusions

Correctional HCWs’ challenging work environment creates unique risk factors for infection with the SARS-CoV-2 virus. Administrative measures taken by the department of corrections may have a significant role in curbing the spread of infection. The findings can help focus preventive measures for reducing the spread of COVID-19 in this unique population.
Display Characterization for Contrast Sensitivity Testing
Authors: de Wit Gerard C.
Published: March 2023

SIGNIFICANCE

Contrast sensitivity measurements using a computer display have been reported to lack accuracy when displaying small contrasts. This report investigates if the characterization/calibration of display luminance may contribute substantively to these kinds of described inaccuracies.

PURPOSE

This study aimed to investigate what errors in contrast sensitivity may result from characterizing a display by fitting a gamma curve through physical or psychophysical luminance measurement data.

METHODS

The luminance functions of four different in-plane switching liquid crystal displays (IPS LCDs) have been measured for all 256 gray levels (the actual luminance function). This has been compared with a gamma-fitted luminance curve (the gamma luminance function). Calculated are the errors in displayed contrast that may arise when assuming the gamma luminance function instead of the actual luminance function.

RESULTS

The amount of error differs considerably between the displays. In general, for large contrasts (Michelson logCS <1.2), the error is acceptable (<<0.15 log unit). However, for smaller contrasts (Michelson logCS >1.5), the error may become unacceptably high (>0.15 log unit).

CONCLUSIONS

To improve the accuracy of testing contrast sensitivity with an LCD, it is necessary to fully characterize the display, measuring the luminance of each gray level instead of fitting a smooth gamma function through limited luminance data.
Triangular Resection Epicanthoplasty: A Novel Method of Minimizing Hypertrophic Scar After Medial Epicanthoplasty
Authors: Kim Taehun , Lee Jun Hyeok , Kim Haksoo , Jun Daiwon
Published: March 2023

Medial epicanthoplasty is a crucial component in Asian cosmetic eyelid surgery. Conventional surgical methods have mandated wide undermining for the purpose of sufficient release. However, excessive undermining may result in hypertrophic scar or webbing deformities. To minimize undesirable results, the authors are proposing a novel approach. From March 2010 to December 2017, a triangular resection epicanthoplasty was performed in 421 Asian patients. The authors’ procedure consists of triangular skin resection, the release of orbicularis oculi muscle and upper half medial epicanthal tendon, and dog ear correction. No complication regarding scarring or webbing was reported. The revision was performed in 18 cases where the patients wanted additional correction. The triangular resection epicanthoplasty offers both optimal results and minimal scar with relative simplicity.
A Novel Approach to Preventing Temporal Hollowing Using Virtual Surgical Planning and Suture Suspension of the Temporalis Muscle
Authors: Kirloskar Kunal M. , Saikaly Kayla , Episalla Nicole C. , Baker Stephen B.
Published: March 2023

Cranioplasty is a well-described technique used to restore the contour and function of calvarial defects using various alloplastic implants and autologous bone grafts. However, unsatisfactory esthetic outcomes after cranioplasty are frequently reported, specifically postoperative temporal hollowing. Temporal hollowing arises when the temporalis is inadequately resuspended after cranioplasty. Several methods to prevent this complication have been described with variable degrees of esthetic improvement, but no single method has proven superior. Herein the authors present a case report demonstrating a novel approach to resuspending the temporalis that incorporates holes in the custom cranial implant to allow for resuspension of the temporalis through suture fixation to the implant.
Diagnostic Accuracy of a Nurse-Led Transient Elastography
Authors: Kumari Sanju , George Mini
Published: March 2023

Once thought rare, liver disease is an emerging cause of significant morbidity and mortality. The rising burden of liver disease necessitates a competent workforce to deliver quality healthcare to patients with liver diseases. Staging liver diseases is essential in disease management. Transient elastography as compared with liver biopsy, the gold standard in staging of the disease, has gained wide acceptance in this field. This study examines the diagnostic accuracy of nurse-led transient elastography in staging fibrosis in chronic liver diseases at a tertiary referral hospital. Audit of records to locate transient elastography and liver biopsy performed within 6 months of interval yielded 193 cases for this retrospective study. A data abstraction sheet was prepared for extracting the relevant data. The content validity index and reliability of the scale were above 0.9. The diagnostic accuracy of liver stiffness evaluation (in kPa) by nurse-led transient elastography to grade fibrosis was categorized as “significant and advanced” and tested against the Ishak staging of liver biopsy. SPSS v.25 was used to perform the analysis. All tests were two-sided at a .01 level of significance. Area under the receiver operating characteristic curve, a graphical plot, illustrated the diagnostic ability of nurse-led transient elastography for significant fibrosis as 0.93 (95% confidence interval [CI] 0.88–0.99; p < .001) and advanced fibrosis as 0.89 (95% CI 0.83–0.93; p < .001). Spearman's ρ correlation between liver stiffness evaluation and liver biopsy was significant (p = .01). Nurse-led transient elastography showed a significant diagnostic accuracy in staging hepatic fibrosis irrespective of the etiology of chronic liver disease. Given the increase in chronic liver disease, introducing more such nurse-led clinics increases the potential for early detection and improves care outcomes for this population.
Barriers and Facilitators to Implementing Simulation-Based Translational Research
Authors: Paganotti Lisa A. , Shope Ron , Calhoun Aaron , McDonald Paige L.
Published: March 2023

Introduction

Translational research has been identified as a research priority for the National Institutes of Health (NIH) and the Society for Simulation in Healthcare (SSH). Despite a larger focus on translational research in recent years, the overall amount of simulation-based translational research remains low. Greater understanding of how to approach translational simulation is required to inform novice simulation and translational researchers. This study sought to answer the following research questions: How do simulation experts describe the barriers and facilitators to implementing translational simulation programs? How do simulation experts describe their various approaches to implementing translational simulation programs? What recommendations do simulation experts describe for overcoming barriers to implementing translational simulation programs?

Methods

A qualitative instrumental case study was used to elicit multiple instances of translational simulation research to gather an in-depth description from study participants. Three data sources were used: documents, semistructured interviews, and a focus group.

Results

Data analyses revealed 5 major themes: clarifying goals and definitions, special considerations, social networking, research, and factors external to the simulation program.

Conclusions

Key findings include a lack of a standardized definitions for translational simulation and simulation-based translational research, the challenge of demonstrating the value of translational simulation, and the need for translational simulation programs to be integrated into departmental quality, patient safety, and risk management work. The findings and advice from the experts in this research can assist new researchers or those encountering challenges in implementing translational simulations.
Polo-like kinase 1 promotes Cdc42-induced actin polymerization for asymmetric division in oocytes
Authors: Yuen Wai Shan , Zhang Qing Hua , Bourdais Anne , Adhikari Deepak , Halet Guillaume , Carroll John
Published: March 2023

Polo-like kinase I (Plk1) is a highly conserved seronine/threonine kinase essential in meiosis and mitosis for spindle formation and cytokinesis. Here, through temporal application of Plk1 inhibitors, we identify a new role for Plk1 in the establishment of cortical polarity essential for highly asymmetric cell divisions of oocyte meiosis. Application of Plk1 inhibitors in late metaphase I abolishes pPlk1 from spindle poles and prevents the induction of actin polymerization at the cortex through inhibition of local recruitment of Cdc42 and Neuronal Wiskott-Aldrich Syndrome protein (N-WASP). By contrast, an already established polar actin cortex is insensitive to Plk1 inhibitors, but if the polar cortex is first depolymerized, Plk1 inhibitors completely prevent its restoration. Thus, Plk1 is essential for establishment but not maintenance of cortical actin polarity. These findings indicate that Plk1 regulates recruitment of Cdc42 and N-Wasp to coordinate cortical polarity and asymmetric cell division.
Structure of the Ndc80 complex and its interactions at the yeast kinetochore–microtubule interface
Authors: Zahm Jacob A. , Jenni Simon , Harrison Stephen C.
Published: March 2023

The conserved Ndc80 kinetochore complex, Ndc80c, is the principal link between mitotic spindle microtubules and centromere-associated proteins. We used AlphaFold 2 (AF2) to obtain predictions of the Ndc80 ‘loop’ structure and of the Ndc80 : Nuf2 globular head domains that interact with the Dam1 subunit of the heterodecameric DASH/Dam1 complex (Dam1c). The predictions guided design of crystallizable constructs, with structures close to the predicted ones. The Ndc80 ‘loop’ is a stiff, α-helical ‘switchback’ structure; AF2 predictions and positions of preferential cleavage sites indicate that flexibility within the long Ndc80c rod occurs instead at a hinge closer to the globular head. Conserved stretches of the Dam1 C terminus bind Ndc80c such that phosphorylation of Dam1 serine residues 257, 265 and 292 by the mitotic kinase Ipl1/Aurora B can release this contact during error correction of mis-attached kinetochores. We integrate the structural results presented here into our current molecular model of the kinetochore–microtubule interface. The model illustrates how multiple interactions between Ndc80c, DASH/Dam1c and the microtubule lattice stabilize kinetochore attachments.
Ultrasonic imaging in highly heterogeneous backgrounds
Authors: Pourahmadian F. , Haddar H.
Published: March 2023

This work formally investigates the differential evolution indicators as a tool for ultrasonic tracking of elastic transformation and fracturing in randomly heterogeneous solids. Within the framework of periodic sensing, it is assumed that the background at time

t
∘

contains (i) a multiply connected set of viscoelastic, anisotropic and piecewise homogeneous inclusions, and (ii) a union of possibly disjoint fractures and pores. The support, material properties and interfacial condition of scatterers in (i) and (ii) are unknown, while elastic constants of the matrix are provided. The domain undergoes progressive variations of arbitrary chemo-mechanical origins such that its geometric configuration and elastic properties at future times are distinct. At every sensing step

t
∘

,

t
1

,
…

, multi-modal incidents are generated by a set of boundary excitations, and the resulting scattered fields are captured over the observation surface. The test data are then used to construct a sequence of wavefront densities by solving the spectral scattering equation. The incident fields affiliated with distinct pairs of obtained wavefronts are analysed over the stationary and evolving scatterers for a suit of geometric and elastic evolution scenarios entailing both interfacial and volumetric transformations. The main theorem establishes the invariance of pertinent incident fields at the loci of static fractures and inclusions between a given pair of time steps, while certifying variation of the same fields over the modified regions. These results furnish a basisfor theoretical justification of differential evolution indicators for imaging in complex composites which, in turn, enable the exclusive tomography of evolution in a background endowed with many unknown features.
Mechanical response of a thick poroelastic gel in contactless colloidal-probe rheology
Authors: Kopecz-Muller Caroline , Bertin Vincent , Raphaël Elie , McGraw Joshua D. , Salez Thomas
Published: March 2023

When a rigid object approaches a soft material in a viscous fluid, hydrodynamic stresses arise in the lubricated contact region and deform the soft material. The elastic deformation modifies in turn the flow, hence generating a soft-lubrication coupling. Moreover, soft elastomers and gels are often porous. These materials may be filled with solvent or uncrosslinked polymer chains, and might be permeable to the surrounding fluid, which further complexifies the description. Here, we derive the point-force response of a semi-infinite and permeable poroelastic substrate. Then, we use this fundamental solution in order to address the specific poroelastic lubrication coupling associated with contactless colloidal-probe methods. In particular, we derive the conservative and dissipative components of the force associated with the oscillating vertical motion of a sphere close to the poroelastic substrate. Our results may be relevant for dynamic surface force apparatus and contactless colloidal-probe atomic force microscopy experiments on soft, living and/or fragile materials, such as swollen hydrogels and biological membranes.
The effectiveness of pseudomagic traits in promoting premating isolation
Authors: Aubier Thomas G. , Bürger Reinhard , Servedio Maria R.
Published: March 2023

Upon the secondary contact of populations, speciation with gene flow is greatly facilitated when the same pleiotropic loci are both subject to divergent ecological selection and induce non-random mating, leading to loci with this fortuitous combination of functions being referred to as ‘magic trait’ loci. We use a population genetics model to examine whether ‘pseudomagic trait’ complexes, composed of physically linked loci fulfilling these two functions, are as efficient in promoting premating isolation as magic traits. We specifically measure the evolution of choosiness, which controls the strength of assortative mating. We show that, surprisingly, pseudomagic trait complexes, and to a lesser extent also physically unlinked loci, can lead to the evolution of considerably stronger assortative mating preferences than do magic traits, provided polymorphism at the involved loci is maintained. This is because assortative mating preferences are generally favoured when there is a risk of producing maladapted recombinants, as occurs with non-magic trait complexes but not with magic traits (since pleiotropy precludes recombination). Contrary to current belief, magic traits may not be the most effective genetic architecture for promoting strong premating isolation. Therefore, distinguishing between magic traits and pseudomagic trait complexes is important when inferring their role in premating isolation. This calls for further fine-scale genomic research on speciation genes.
Cellular and environmental dynamics influence species-specific extents of organelle gene retention
Authors: García Pascual Belén , Nordbotten Jan M. , Johnston Iain G.
Published: March 2023

Mitochondria and plastids rely on many nuclear-encoded genes, but retain small subsets of the genes they need to function in their own organelle DNA (oDNA). Different species retain different numbers of oDNA genes, and the reasons for these differences are not completely understood. Here, we use a mathematical model to explore the hypothesis that the energetic demands imposed by an organism’s changing environment influence how many oDNA genes it retains. The model couples the physical biology of cell processes of gene expression and transport to a supply-and-demand model for the environmental dynamics to which an organism is exposed. The trade-off between fulfilling metabolic and bioenergetic environmental demands, and retaining genetic integrity, is quantified for a generic gene encoded either in oDNA or in nuclear DNA. Species in environments with high-amplitude, intermediate-frequency oscillations are predicted to retain the most organelle genes, whereas those in less dynamic or noisy environments the fewest. We discuss support for, and insight from, these predictions with oDNA data across eukaryotic taxa, including high oDNA gene counts in sessile organisms exposed to day-night and intertidal oscillations (including plants and algae) and low counts in parasites and fungi.
Artificial light at night increases top-down pressure on caterpillars: experimental evidence from a light-naive forest
Authors: Deitsch John F. , Kaiser Sara A.
Published: March 2023

Artificial light at night (ALAN) is a globally widespread and expanding form of anthropogenic change that impacts arthropod biodiversity. ALAN alters interspecific interactions between arthropods, including predation and parasitism. Despite their ecological importance as prey and hosts, the impact of ALAN on larval arthropod stages, such as caterpillars, is poorly understood. We examined the hypothesis that ALAN increases top-down pressure on caterpillars from arthropod predators and parasitoids. We experimentally illuminated study plots with moderate levels (10–15 lux) of LED lighting at light-naive Hubbard Brook Experimental Forest, New Hampshire. We measured and compared between experimental and control plots: (i) predation on clay caterpillars, and (ii) abundance of arthropod predators and parasitoids. We found that predation rates on clay caterpillars and abundance of arthropod predators and parasitoids were significantly higher on ALAN treatment plots relative to control plots. These results suggest that moderate levels of ALAN increase top-down pressure on caterpillars. We did not test mechanisms, but sampling data indicates that increased abundance of predators near lights may play a role. This study highlights the importance of examining the effects of ALAN on both adult and larval life stages and suggests potential consequences of ALAN on arthropod populations and communities.
Cognitive performance is linked to survival in free-living African striped mice
Authors: Rochais Celine , Schradin Carsten , Pillay Neville
Published: March 2023

Cognition is shaped by evolution and is predicted to increase fitness. However, the link between cognition and fitness in free-living animals is unresolved. We studied the correlates of cognition and survival in a free-living rodent inhabiting an arid environment. We tested 143 striped mice (
Rhabdomys pumilio
) using a battery of cognitive tests, including: (i) an attention task, (ii) two problem-solving tasks, (iii) a learning and reversal learning task, and (iv) an inhibitory control task. We related cognitive performance with days of survival. Better problem-solving and inhibitory control performance were significant correlates of survival. Surviving males showed greater reversal learning which may be related to sex-specific behavioural and life-history characteristics. Specific cognitive traits and not a composite measure of general intelligence underpins fitness in this free-living rodent population, enhancing our understanding of the evolution of cognition in non-human animals.
Cognitive trends in an urban Indian elderly community: Glycated hemoglobin and geriatric depression play a bigger role than age
Authors: Dongaonkar Bhaktee , Singh Arman Deep , Hurakadli Swathi B , Godbole Ashwini
Published: March 2023

Objectives

To explore the cognitive profile in urban Indian older adults and observe the prevalence of cognitive impairment associated with age, glycated hemoglobin (HbA1c) levels, vitamin B12, and other psychosocial factors

Methods

Urban community dwelling older adults (55-85years, n=123) underwent a detailed demographic and cognitive assessment comprising of tests from different cognitive domains – memory, executive function, visuospatial abilities, and verbal fluency. Serum samples were collected from a subset of participants (n=60) to determine HbA1c and vitamin B12 levels.

Results

Performance in all cognitive domains declined with age. The decline became prominent around age 70. HbA1c correlated inversely with processing speed and executive function. Vitamin B12 did not correlate with performance on any cognitive test. Geriatric depression correlated inversely with visuospatial abilities. Surprisingly, stepwise multiple regression revealed that HbA1c and geriatric depression contributed to 28% variance on Montreal Cognitive Assessment whereas participant age did not contribute significantly. Mild Cognitive Impairment (MCI) was observed in 17% of participants. Participants classified as MCI had higher levels of HbA1c and geriatric depression, and lower performance in all cognitive domains compared to non-MCI participants.

Conclusion

Although cognitive performance declined with age, HbA1c and geriatric depression played a greater role than age in predicting cognitive decline. This study highlights the prevalence of metabolism linked changes in cognition in community dwelling Indian older adults.
Age-related differences in the functional topography of the locus coeruleus: implications for cognitive and affective functions
Authors: Veréb Dániel , Mijalkov Mite , Canal-Garcia Anna , Chang Yu-Wei , Gomez-Ruis Emiliano , Gerboles Blanca Zufiria , Kivipelto Miia , Svenningsson Per , Zetterberg Henrik , Volpe Giovanni , Betts Mathew J. , Jacobs Heidi , Pereira Joana B.
Published: March 2023

The locus coeruleus (LC) is an important noradrenergic nucleus that has recently attracted a lot of attention because of its emerging role in cognitive and psychiatric disorders. Although previous histological studies have shown that the LC has heterogeneous connections and cellular features, no studies have yet assessed its functional topography in vivo, how this heterogeneity changes over aging and whether it is associated with cognition and mood. Here we employ a gradient-based approach to characterize the functional heterogeneity in the organization of the LC over aging using 3T resting-state fMRI in a population-based cohort aged from 18 to 88 years old (Cambridge Centre for Ageing and Neuroscience cohort, n=618). We show that the LC exhibits a rostro-caudal functional gradient along its longitudinal axis, which was replicated in an independent dataset (Human Connectome Project 7T dataset, n=184). Although the main rostro-caudal direction of this gradient was consistent across age groups, its spatial features varied with increasing age, emotional memory and emotion regulation. More specifically, a loss of rostral-like connectivity, more clustered functional topography and greater asymmetry between right and left LC gradients was associated with higher age and worse behavioral performance. Furthermore, participants with higher-than-normal Hospital Anxiety and Depression Scale ratings exhibited alterations in the gradient as well, which manifested in greater asymmetry. These results provide an in vivo account of how the functional topography of the LC changes over aging, and imply that spatial features of this organization are relevant markers of LC-related behavioral measures and psychopathology.
Screening for amyotrophic lateral sclerosis through interactions with an internet search engine
Authors: Yom-Tov Elad , Navar Indu , Fraenkel Ernest , Berry James D.
Published: March 2023

Amyotrophic lateral sclerosis (ALS), a motor neuron disease, remains a clinical diagnosis with a diagnostic delay of over a year. Here we examine the possibility that interactions with an internet search engine could be used to help screen for ALS. We identified 285 anonymous Bing users whose queries indicated that they had been diagnosed with ALS and matched them to 1) 3276 control users and 2) 1814 users whose searches indicated they had ALS disease mimics. We tested whether the ALS group could be distinguished from controls and disease mimics based on search engine query data. Finally, we conducted a prospective validation from participants who provided access to their Bing search data. The model distinguished between the ALS group and controls with an area under the curve (AUC) of 0.81. Model scores for the ALS group differed from the disease mimics group (ranksum test, P<0.05 with Bonferrini correction). Mild cognitive impairment could not be distinguished from ALS (NS). In the prospective analysis, the model reached an AUC of 0.74. These results suggest that interactions with search engines could be used as a tool to assist in screening for ALS, to reduce diagnostic delay.
End to end stroke triage using cerebrovascular morphology and machine learning
Authors: Deshpande Aditi , Elliott Jordan , Jiang Bin , Tahsili-Fahadan Pouya , Kidwell Chelsea , Wintermark Max , Laksari Kaveh
Published: March 2023

Background

Rapid and accurate triage of acute ischemic stroke (AIS) is essential for early revascularization and improved patient outcomes. Response to acute reperfusion therapies varies significantly based on patient-specific cerebrovascular anatomy that governs cerebral blood flow. We present an end-to-end machine learning approach for automatic stroke triage.

Methods

Employing a validated convolutional neural network (CNN) segmentation model for image processing, we extract each patient’s cerebrovasculature and its morphological features from baseline non-invasive angiography scans. These features are used to detect occlusion’s presence and the site automatically, and for the first time, to estimate collateral circulation without manual intervention. We then use the extracted cerebrovascular features along with commonly used clinical and imaging parameters to predict the 90-day functional outcome for each patient.

Results

The CNN model achieved a segmentation accuracy of 94%. The automatic stroke detection algorithm had a sensitivity and specificity of 92% and 94%, respectively. The models for occlusion site detection and automatic collateral grading reached 96% and 87.2% accuracy, respectively. Incorporating the automatically extracted cerebrovascular features significantly improved the 90-day outcome prediction accuracy from 0.63 to 0.83.

Conclusions

The fast, automatic, and comprehensive model presented here can improve stroke diagnosis, aid collateral assessment, and enhance prognostication for treatment decisions, using cerebrovascular morphology.
Experiences of care-seeking behaviour for sexually transmitted infections among gay and bisexual men: A phenomenological study
Authors: Adoma Prince Owusu , Yeboah Snr Cecilia Adomah , Nantomah Bismark , Manu Emmanuel , Kushitor Mawuli
Published: March 2023

Introduction

Gay and bisexual men (GBM) are stigmatized in the Ghanaian society and that negatively affect their care-seeking behaviour. We sought to understand the experiences of care-seeking behaviour (CSB) for STIs among gay and bisexual men in Bono region, Ghana.

Methods

A respondent-driven sampling was used to collect data from 17 gay and bisexual men in Bono region based on phenomenological qualitative approach. The data were thematically analysed using the Atlas.ti software.

Results

Results were presented under various themes with appropriate accompanying excerpts. Two broad themes emerged from the data; personal and health system experiences of treating STIs. Personal experiences such as economic conditions, knowledge on STI, marital experiences and bisexual’s partner awareness of sexual orientation had influences on CSB. Experience with the cost of treatment, stigmatisation by health care workers (HCW) and perceived quality healthcare were the health system factors found to influence CSB.

Conclusion

To help improve STIs care-seeking behaviour, government need to encourage and economically empower GBM, while at the same time, improving their knowledge on STI prevention and control. The National Health Authority should intensify and monitor the implementation of the national health insurance at the private healthcare sectors without favour and discrimination for gay and bisexual men.
Improving Computational Fluid Dynamics Simulations of Coiled Aneurysms Using Finite Element Modeling
Authors: Fillingham Patrick , Bhathal Julia Romero , Marsh Laurel M.M. , Barbour Michael C. , Kurt Mehmet , Ionita Ciprian N. , Davies Jason M. , Aliseda Alberto , Levitt Michael R.
Published: March 2023

Cerebral aneurysms are a serious clinical challenge, with ∼half resulting in death or disability. Treatment via endovascular coiling significantly reduces the chances of rupture, but the technique has failure rates between 25-40%. This presents a pressing need to develop a method for determining optimal coil deployment strategies. Quantification of aneurysm hemodynamics through computational fluid dynamics (CFD) has the potential to significantly improve the understanding of the mechanics of aneurysm coiling and improve treatment outcomes, but accurately representing the coil mass in CFD simulations remains a challenge. We have used the Finite Element Method (FEM) for simulating patient-specific coil deployment based on mechanical properties and coil geometries provided by the device manufacturer for n=4 ICA aneurysms for which 3D printedin vitromodels were also generated, coiled, and scanned using ultra-high resolution synchrotron micro-CT. The physical and virtual coil geometries were voxelized onto a binary structured grid and porosity maps were generated for geometric comparison. The average binary accuracy score is 0.836 and the average error in porosity map is 6.3%. We then conduct patient-specific CFD simulations of the aneurysm hemodynamics using virtual coils geometries, micro-CT generated oil geometries, and using the porous medium method to represent the coil mass. Hemodynamic parameters of interest including were calculated for each of the CFD simulations. The average error across hemodynamic parameters of interest is ∼19%, a 58% reduction from the average error of the porous media simulations, demonstrating a marked improvement in the accuracy of CFD simulations using FEM generated coil geometries.
Challenging the gold standard: critical limitations in clinical detection of drug-resistant tuberculosis
Authors: Danchuk Sarah N. , Solomon Ori E. , Kohl Thomas A. , Niemann Stefan , van Soolingen Dick , van Ingen Jakko , Michael Joy S. , Behr Marcel A.
Published: March 2023

Heteroresistant infections - defined as infections in which minority drug-resistant (DR) populations are present - are a challenge in infectious disease control. InMycobacterium tuberculosis, heteroresistance poses challenges in diagnosis and has been linked with poor treatment outcomes. We compared the analytic sensitivity of molecular methods, such as GeneXpert and whole genome sequencing (WGS) in detecting heteroresistance when compared to the ‘gold standard’ phenotypic assay: the agar proportion method (APM). Using defined mono-resisitant BCG strains we determined the limit of detection (LOD) of rifampin-R (RIF-R) detection was 1% using APM, 60% using Xpert MTB/RIF and 10% using Xpert MTB/RIF Ultra. To evaluate clinical WGS pipelines, a blinded panel of BCG mixtures was sent to 3 clinical labs. These were composed of either a) RIF-R plus isoniazid-R (INH-R) BCG or b) fluoroquinolone-R (FQ-R) plus clofazimine-R/bedaquiline-R (CLZ/BDQ-R) BCG. No labs called resistance at 1%; all labs called RIF-R at 10% or greater and two out of three labs reported FQ-R at 10%. Two labs were able to detect the majority population (either INH-R or CLZ/BDQ-R) at 50%. Importantly, where labs did not report resistance in the majority population, the mutations were present in the raw data but excluded from the final analysis. In conclusion, the gold standard APM more reliably detects minority resistant populations than molecular tests. Further research is required to determine whether the higher LOD of molecular tests is associated with deleterious patient outcomes and the potential effects on transmission of resistance at the population level.
Rotamer Density Estimator is an Unsupervised Learner of the Effect of Mutations on Protein-Protein Interaction
Authors: Luo Shitong , Su Yufeng , Wu Zuofan , Su Chenpeng , Peng Jian , Ma Jianzhu
Published: March 2023

Abstract

Protein-protein interactions are crucial to many biological processes, and predicting the effect of amino acid mutations on binding is important for protein engineering. While data-driven approaches using deep learning have shown promise, the scarcity of annotated experimental data remains a major challenge. In this work, we propose a new approach that predicts mutational effects on binding using the change in conformational flexibility of the protein-protein interface. Our approach, named Rotamer Density Estimator (RDE), employs a flow-based generative model to estimate the probability distribution of protein side-chain conformations and uses entropy to measure flexibility. RDE is trained solely on protein structures and does not require the supervision of experimental values of changes in binding affinities. Furthermore, the unsupervised representations extracted by RDE can be used for downstream neural network predictions with even greater accuracy. Our method outperforms empirical energy functions and other machine learning-based approaches.
Coarse-grained Modeling and Experimental Investigation of the Viscoelasticity of Human Gut Mucus and Nanoparticle Dynamics
Authors: Zhao Liming , Arias Sandra L. , Brito Ilana L. , Yeo Jingjie
Published: March 2023

A thick layer of mucus covering the gastrointestinal tract acts as an innate barrier guarding the epithelial surface. The high molecular weight and cross-linked glycoproteins (mucins), the major building blocks of mucus, can effectively obstruct or trap invading noxious substances, such as detrimental bacteria and virus. The mucus layer as well as any trapped material can be regularly removed by the friction force from food flow and gastrointestinal peristalsis, the process of which primarily relies on the viscoelastic and shear-thinning properties. Conversely, the process by which beneficial substances, such as drug nanoparticles, cross the mucus layer and contact the epithelium is also influenced by the chemical and rheological properties of the mucus layer. Gastrointestinal disorders, most notably colitis, are often accompanied by changes to the mucosal structure. In this study, we experimentally characterized the viscoelasticity and dynamic viscosity of mucus collected from human intestinal cells. In addition, we developed a bi-component mesoscopic-scale mucus model that contained Muc2, the dominant mucin secreted in healthy individuals, and Muc5AC, which is secreted by intestinal goblet cells in certain intestinal disorders. This model enabled us to study the effects of cross-linking and mucin concentration on rheological properties of mucus. Furthermore, we quantified changes in the diffusion dynamics of nanoparticles in mucus networks caused by factors such as the size of nanoparticles, nanoparticle-mucin interactions, and the degree of mucin cross-linking.
Genome Sequencing and Comprehensive Rare Variant Analysis of 465 Families with Neurodevelopmental Disorders
Authors: Sanchis-Juan Alba , Megy Karyn , Stephens Jonathan , Ricaurte Camila Armirola , Dewhurst Eleanor , Low Kayyi , French Courtney E , Grozeva Detelina , Stirrups Kathleen , Erwood Marie , McTague Amy , Penkett Christopher J , Shamardina Olga , Tuna Salih , Daugherty Louise C. , Gleadall Nicholas , Duarte Sofia T , Hedrera-Fernández Antonio , Vogt Julie , Ambegaonkar Gautam , Chitre Manali , Josifova Dragana , Kurian Manju A , Parker Alasdair , Rankin Julia , Reid Evan , Wakeling Emma , Wassmer Evangeline , Woods C Geoffrey ,   NIHR-BioResource, Raymond F Lucy , Carss Keren J
Published: March 2023

Purpose

Despite significant progress in unravelling the genetic causes of neurodevelopmental disorders (NDDs), a substantial proportion of individuals with NDDs remain without a genetic diagnosis following microarray and/or exome sequencing. Here we aimed to assess the power of short-read genome sequencing (GS), complemented with long-read GS, to identify causal variants in NDD participants from the NIHR BioResource project.

Methods

Short-read GS was conducted on 692 individuals (489 affected and 203 unaffected relatives) from 465 families. Additionally, long-read GS was performed on five affected individuals who had structural variants (SVs) in technically challenging regions, complex SVs, or required distal variant phasing.

Results

Causal variants were identified in 36% affected individuals (177/489) and a further 26% (129/489) had a variant of uncertain significance, after multiple rounds of re-analysis. Among all reported variants, 88% (333/380) were SNVs/indels, and the remainder were structural variants (SVs), non-coding, and mitochondrial variants. Furthermore, long-read GS facilitated resolution of challenging SVs and invalidated variants of difficult interpretation from short-read GS.

Conclusion

This study demonstrates the value of short-read GS, complemented with long-reads, to investigate the genetic causes of NDDs. GS provides a comprehensive and unbiased method to identify all types of variants throughout the nuclear and mitochondrial genome in NDD individuals.
Trio-based GWAS identifies novel associations and subtype-specific risk factors for cleft palate
Authors: Robinson Kelsey , Mosley Trenell J. , Rivera-González Kenneth S. , Jabbarpour Christopher R. , Curtis Sarah W. , Adeyemo Wasiu Lanre , Beaty Terri H. , Butali Azeez , Buxó Carmen J. , Cutler David J. , Epstein Michael P. , Gowans Lord JJ , Hecht Jacqueline T. , Murray Jeffrey C. , Shaw Gary M. , Uribe Lina Moreno , Weinberg Seth M. , Brand Harrison , Marazita Mary L. , Lipinski Robert J. , Leslie Elizabeth J.
Published: March 2023

Orofacial clefts (OFCs) are the most common craniofacial birth defects and are often categorized into two etiologically distinct groups: cleft lip with or without cleft palate (CL/P) and isolated cleft palate (CP). CP is highly heritable, but there are still relatively few established genetic risk factors associated with its occurrence compared to CL/P. Historically, CP has been studied as a single phenotype despite manifesting across a spectrum of defects involving the hard and/or soft palate. We performed GWAS using transmission disequilibrium tests using 435 case-parent trios to evaluate broad risks for any cleft palate (ACP, n=435), as well as subtype-specific risks for any cleft soft palate (CSP, n=259) and any cleft hard palate (CHP, n=125). We identified a single genome-wide significant locus at 9q33.3 (lead SNP rs7035976, p=4.24×10−8) associated with CHP. One gene at this locus, angiopoietin-like 2 (ANGPTL2), plays a role in osteoblast differentiation. It is expressed in craniofacial tissue of human embryos, as well as in the developing mouse palatal shelves. We found 19 additional loci reaching suggestive significance (p<5×10−6), of which only one overlapped between groups (chromosome 17q24.2, ACP and CSP). Odds ratios (ORs) for each of the 20 loci were most similar across all three groups for SNPs associated with the ACP group, but more distinct when comparing SNPs associated with either the CSP or CHP groups. We also found nominal evidence of replication (p<0.05) for 22 SNPs previously associated with cleft palate (including CL/P). Interestingly, most SNPs associated with CL/P cases were found to convey the opposite effect in those replicated in our dataset for CP only. Ours is the first study to evaluate CP risks in the context of its subtypes and we provide newly reported associations affecting the broad risk for CP as well as evidence of subtype-specific risks.
Real-time Dissection and Forecast of Infection Dynamics during a Pandemic
Authors: Schulz Steven , Pastor Richard , Koyuncuoglu Cenk , Crawford Forrest W. , Zernick Detlef , Karch André , Rüdiger Sten
Published: March 2023

Pandemic preparedness requires institutions, including public health authorities and governments, to detect, survey and control outbreaks. To maintain an accurate, quantitative and up-to-date picture of an epidemic crisis is key. For SARS-CoV-2, this was mostly achieved by ascertaining incidence numbers and the effective reproductive number (Reff), which counts how many people an infected person is likely to infect on average. These numbers give strong hints on past infection dynamics in a population but fail to clearly characterize current and future dynamics as well as potential effects of pharmaceutical and non-pharmaceutical interventions. We show that, by using and combining infection surveillance and population-scale contact statistics, we can obtain a better understanding of the drivers of epidemic waves and the effectiveness of interventions. This approach can provide a real-time picture, thus saving not only many lives by quickly allowing adaptation of the health policies but also alleviating economic and other burdens if an intervention proves ineffective. We factorizeReffinto contacts and relative transmissibility: Both signals can be used, individually and combined, to identify driving forces of an epidemic, monitoring and assessing interventions, as well as projecting an epidemic’s future trajectory. Using data for SARS-CoV-2 and Influenza from 2019 onward in Germany, we provide evidence for the usefulness of our approach. In particular, we find that the effects from physical distancing and lockdowns as well as vaccination campaigns are dominant.
Examining Longitudinal Markers of Bladder Cancer Recurrence Through a Semi-Autonomous Machine Learning System for Quantifying Specimen Atypia from Urine Cytology
Authors: Levy Joshua J. , Chan Natt , Marotti Jonathan D. , Rodrigues Nathalie J. , Ismail A. Aziz O. , Kerr Darcy A. , Gutmann Edward J. , Glass Ryan E. , Dodge Caroline P. , Suriawinata Arief A. , Christensen Brock , Liu Xiaoying , Vaickus Louis J.
Published: March 2023

Urine cytology (UC) is generally considered the primary approach for screening for recurrence of bladder cancer. However, it is currently unclear how best to use cytological exams themselves for the assessment and early detection of recurrence, beyond identifying a positive finding which requires more invasive methods to confirm recurrence and decide on therapeutic options. As screening programs are frequent, and can be burdensome, finding quantitative means to reduce this burden for patients, cytopathologists and urologists is an important endeavor and can improve both the efficiency and reliability of findings. Additionally, identifying ways to risk-stratify patients is crucial for improving quality of life while reducing the risk of future recurrence or progression of the cancer. In this study, we leveraged a computational machine learning tool, AutoParis-X, to extract imaging features from UC exams longitudinally to study the predictive potential of urine cytology for assessing recurrence risk. This study examined how the significance of imaging predictors changes over time before and after surgery to determine which predictors and time periods are most relevant for assessing recurrence risk. Results indicate that imaging predictors extracted using AutoParis-X can predict recurrence as well or better than traditional cytological / histological assessments alone and that the predictiveness of these features is variable across time, with key differences in overall specimen atypia identified immediately before tumor recurrence. Further research will clarify how computational methods can be effectively utilized in high volume screening programs to improve recurrence detection and complement traditional modes of assessment.
A multidimensional analysis reveals distinct immune phenotypes and the composition of immune aggregates in pediatric acute myeloid leukemia
Authors: Koedijk Joost B. , van der Werf Inge , Penter Livius , Vermeulen Marijn A. , Barneh Farnaz , Perzolli Alicia , Meesters-Ensing Joyce I. , Metselaar Dennis S. , Margaritis Thanasis , Fiocco Marta , de Groot-Kruseman Hester A. , Moeniralam Rubina , Bang Christensen Kristina , Porter Billie , Pfaff Kathleen , Garcia Jacqueline S. , Rodig Scott J. , Wu Catherine J. , Hasle Henrik , Nierkens Stefan , Belderbos Mirjam E. , Zwaan C. Michel , Heidenreich Olaf
Published: March 2023

Because of the low mutational burden and consequently, fewer potential neoantigens, children with acute myeloid leukemia (AML) are thought to have a T cell-depleted or ‘cold’ tumor microenvironment and may have a low likelihood of response to T cell-directed immunotherapies. Understanding the composition, phenotype, and spatial organization of T cells and other microenvironmental populations in the pediatric AML bone marrow (BM) is essential for informing future immunotherapeutic trials about targetable immune-evasion mechanisms specific to pediatric AML. Here, we conducted a multidimensional analysis of the tumor immune microenvironment in pediatric AML and non-leukemic controls. We demonstrated that nearly one-third of pediatric AML cases has an immune-infiltrated BM, which is characterized by a decreased ratio of M2-to M1-like macrophages. Furthermore, we detected the presence of large T cell networks, both with and without colocalizing B cells, in the BM and dissected the cellular composition of T- and B cell-rich aggregates using spatial transcriptomics. These analyses revealed that these aggregates are hotspots of CD8+T cells, memory B cells, plasma cells and/or plasmablasts, and M1-like macrophages. Collectively, our study provides a multidimensional characterization of the BM immune microenvironment in pediatric AML and indicates starting points for further investigations into immunomodulatory mechanisms in this devastating disease.