bluuebunny/crossref_metadata_2025_split huggingface dataset:
Orbital Vascular Malformations: Relationship Between Enophthalmos and Clinically Apparent Distensibility with Valsalva
Authors: Cheng Sarah , Roelofs Kelsey A. , Pirakitikulr Nathan , Rootman Daniel B. 
Published: March 2023

Purpose:
Determining the hemodynamic characteristics of an orbital vascular malformation is a critical step in management. The purpose of this study is to assess the relationship between enophthalmos and clinically apparent distensibility of orbital vascular malformations, to optimize imaging and treatment.

Methods:
In this cross-sectional cohort study consecutive patients at a single institution were screened for study entry. Data extracted included age, sex, Hertel measurements, presence or absence of distensibility during the Valsalva maneuver, whether lesions were primarily venous or lymphatic based on imaging, and location of the lesion relative to the globe. Enophthalmos was defined as ≥ 2 mm difference from the opposite side. Parametric and nonparametric statistics were used, and linear regression was performed to examine factors predictive of Hertel measurement.

Results:
Twenty-nine patients met the inclusion criteria. Relative enophthalmos ≥2 mm was significantly associated with distensibility (p = 0.03; odds ratio = 5.33). Distensibility and venous dominant morphology were the 2 most important factors associated with enophthalmos on regression analysis. The relative position of the lesion anterior or posterior to the globe did not have a significant bearing on baseline enophthalmos.

Conclusions:
The presence of enophthalmos increases the likelihood that an orbital vascular malformation is distensible. This group of patients was also more likely to be characterized by venous dominant malformations. Baseline clinical enophthalmos may serve as a useful surrogate marker for distensibility and venous dominance, which may be useful in guiding the selection of appropriate imaging.
Sex differences in pain expressed by patients across diverse disease states: individual patient data meta-analysis of 33,957 participants in 10 randomized controlled trials
Authors: Li Jessica X.L. , Wang Xia , Henry Amanda , Anderson Craig S. , Hammond Naomi , Harris Katie , Liu Hueiming , Loffler Kelly , Myburgh John , Pandian Jeyaraj , Smyth Brendan , Venkatesh Balasubramanian , Carcel Cheryl , Woodward Mark 
Published: March 2023

Abstract
The experience of pain is determined by many factors and has a significant impact on quality of life. This study aimed to determine sex differences in pain prevalence and intensity reported by participants with diverse disease states in several large international clinical trials. Individual participant data meta-analysis was conducted using EuroQol-5 Dimension (EQ-5D) questionnaire pain data from randomised controlled trials published between January 2000 and January 2020 and undertaken by investigators at the George Institute for Global Health. Proportional odds logistic regression models, comparing pain scores between females and males and fitted with adjustments for age and randomized treatment, were pooled in a random-effects meta-analysis. In 10 trials involving 33,957 participants (38% females) with EQ-5D pain score data, the mean age ranged between 50 and 74. Pain was reported more frequently by females than males (47% vs 37%; P < 0.001). Females also reported greater levels of pain than males (adjusted odds ratio 1.41, 95% CI 1.24-1.61; P < 0.001). In stratified analyses, there were differences in pain by disease group (P for heterogeneity <0.001), but not by age group or region of recruitment. Females were more likely to report pain, and at a higher level, compared with males across diverse diseases, all ages, and geographical regions. This study reinforces the importance of reporting sex-disaggregated analysis to identify similarities and differences between females and males that reflect variable biology and may affect disease profiles and have implications for management.
Blood prestin levels in COVID-19 patients
Authors: Turan Mahfuz , Alp Hamit Hakan , Yildiz Hanifi , Baran Ali İrfan , Ekin Selami , Akin Ramazan , Arisoy Ahmet , Çetin Yaser Said , Turan Aydin , Bozan Nazim 
Published: March 2023

Background:
Many studies have found that viral infections affect different tissues, including the inner ear. Coronavirus disease 2019 (COVID-19), a viral infection, is a significant health problem worldwide. Prestin is a motor protein with important functions both in the outer hair cells of the inner ear and in cardiac tissue. In addition, prestin is promising as an early biomarker in the detection of ototoxicity. To determine the severity of infection in COVID-19 patients and to determine whether other tissues are affected by the infection, lactate dehydrogenase (LDH), C-reactive protein (CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase MB (CK-MB), biochemical markers such as ferritin and D-dimer are used. This study aimed to compare prestin levels in patients with COVID-19 and healthy volunteers.

Methods:
In blood samples taken from 45 patients diagnosed with COVID-19 and 40 healthy volunteers, prestin levels were determined with the kit that used an enzyme-linked immunosorbent assay method and was commercially available. At the same time, LDH, CRP, ALT, AST, CK-MB, ferritin, and D-dimer levels were also detected in both patients and healthy control groups and correlations with prestin levels were examined.

Results:
The main result of our study is that serum prestin levels in COVID-19 patients are significantly higher than in healthy controls (p < 0.001). In addition, a statistically significant strong positive correlation was found between prestin-LDL (r = 0.537, p = 0.001), prestin-CRP (r = 0.654, p = 0.001), and prestin-D-dimer (r = 0.659, p = 0.001).

Conclusion:
The levels of prestin, a motor protein in inner ear outer hair cells and cardiac myocytes, were found to be higher in COVID-19 patients than in healthy volunteers. It also showed a positive correlation with CRP and D-dimer. This may be associated with systemic dysfunction.
Canada's Aging Federal Prison Population
Authors: Johansson Jim A. , Holmes Dave , Paradis-Gagné Etienne 
Published: March 2023

ABSTRACT
The Canadian federal prison population is increasingly aging within institutions that were never intended or designed to meet the complex medical and mental health needs of older incarcerated persons. Increasing numbers of incarcerated persons are “aging in place,” and many are dying within federal correctional institutions. Persons convicted of sexual offenses comprise a large—and growing—proportion of this aging population. The Correctional Investigator Canada has recently called for an expansion of access to compassionate release for the aging federal prison population, yet little progress has been made. In this article, we explore the significant challenges faced by the aging population in federal institutions, including insufficient access to appropriate care, challenges in application for compassionate release, and how questions of risk may affect the potential for community transfer. Questions of risk overshadow decisions on early release of incarcerated persons, especially those convicted of sexual offenses. Nurses play a central role in the provision of care to aging incarcerated persons and in advocacy for better access to services when a patient's needs cannot be met within the institution. This article presents a call to action for forensic nurses in Canada (and beyond) to advocate for both improved services within federal correctional institutions and for expedited access to compassionate release of aging incarcerated persons, especially those nearing end of life. The significant disparity in access to health care for aging incarcerated persons compared with their nonincarcerated counterparts represents a significant concern.
An Experiential Approach to Canine-Assisted Learning in Corrections for Prisoners Who Use Substances
Authors: Kosteniuk Brynn , Dell Colleen Anne , Cruz Maria , Chalmers Darlene 
Published: March 2023

ABSTRACT
Canine-assisted interventions are a promising approach to help address substance use and mental health issues in prisons. However, canine-assisted interventions in prisons have not been well explored in relation to experiential learning (EL) theory, despite canine-assisted interventions and EL aligning in many ways. In this article, we discuss a canine-assisted learning and wellness program guided by EL for prisoners with substance use issues in Western Canada. Letters written by participants to the dogs at the conclusion of the program suggest that such programming can help shift relational dynamics and the prison learning environment, benefit prisoners' thinking patterns and perspectives, and help prisoners generalize and apply key learnings to recovery from addiction and mental health challenges. Implications are discussed in relation to clinicians' practices, prisoners' health and wellness, and prison programming.
Prolonged prothrombin time does not correlate with clinical bleeding symptoms in newly diagnosed paediatric leukaemia patients
Authors: Al-Ghafry Maha , Haimed Abraham , Su Julia , Acharya Suchitra S. 
Published: March 2023

Prolonged prothrombin time (PT) and/or activated partial thromboplastin time (aPTT) are frequently seen in newly diagnosed paediatric leukaemia patients (NDPLP), which can lead to delayed diagnostic and therapeutic procedures due to concern for bleeding.
A single-centre retrospective chart review of NDPLP between 2015 and 2018 aged 1–21 years.
We analysed 93 NDPLP of whom 33.3% had bleeding symptoms within 30 days of presentation, predominantly mucosal bleeding (80.6%) and petechiae (64.5%). Median laboratory values: white blood cell count 15.7, haemoglobin 8.1, platelets 64, PT 13.2 and a PTT 31. Red blood cells were administered in 41.2%, platelets in 52.9%, fresh frozen plasma in 7.8% and vitamin K in 21.6% of patients. Prolonged PT was found in 54.8% of patients, while aPTT was prolonged in 5.4%. Anaemia and thrombocytopenia did not correlate with prolonged PT (P = 0.73 and P = 0.18, respectively), or prolonged aPTT (P = 0.52 and 0.42). Leukocytosis showed significant correlation with elevated PT (P < 0.001), but not aPTT (P = 0.3). Bleeding symptoms upon presentation did not correlate with prolonged PT (P = 0.83), prolonged aPTT (P = 1) or anaemia (P = 0.06) but had a significant correlation with thrombocytopenia (P ≤ 0.0001).
Therefore, a prolonged PT in NDPLP may not necessitate the reflexive use of blood product replacement, in the absence of significant bleeding, which is likely related to leukocytosis than to a true coagulopathy.
The Impact of Language Discordance on Patients’ Perception of a Clinical Encounter and Trust in Provider
Authors: Caldwell Lauren , Halder Gabriela E. , White Amanda B. , High Rachel A. , Wright Michelle L. , Rogers Rebecca G. 
Published: March 2023

Importance
The impact of language discordance on care for Spanish-speaking patients with pelvic floor disorders is unknown.

Objective
The aim of this study was to compare the impact of language concordance with the impact of language discordance on the patient experience and trust in their provider.

Methods
This cross-sectional cohort study enrolled English- and Spanish-speaking patients during initial evaluation in a urogynecology clinic. English- and Spanish-speaking patients seen by native English- or Spanish-speaking providers were recruited to the language-concordant group. The language-discordant group included Spanish-speaking patients seen with a translator or by nonnative Spanish-speaking providers. Patients completed the Trust in Physician Scale and the Consumer Assessment of Healthcare Providers and Systems Clinician and Group Survey (CG-CAHPS). Patients and providers rated the provider's Spanish proficiency on a 10-point scale from 0 (low) to 10 (high). Symptom bother questionnaires were completed 4–6 months after enrollment.

Results
Eighty women were recruited, with 40 in each group. Mean age was 55.4 ± 12.9 years. The majority identified as White (75%) and Hispanic (77.5%). Trust in Physician Scale scores were similar between groups (46.2 ± 8.5 vs 44.4 ± 7.5, P > 0.05). The provider communication, provider rating, and recommendation domains of the CG-CAHPS did not differ between groups (all P > 0.05). Provider self-rating of Spanish proficiency was lower than patient ratings (7.5 ± 1.8 vs 9.8 ± 0.5, P < 0.001). There was no difference between groups in symptom bother at 4–6 months (all P > 0.05).

Conclusions
Patient-provider language discordance does not affect patient trust in the provider or perception of the encounter as measured by the Trust in Physician Scale and CG-CAHPS questionnaires.
Being Bayesian in the 2020s: opportunities and challenges in the practice of modern applied Bayesian statistics
Authors: Bon Joshua J. , Bretherton Adam , Buchhorn Katie , Cramb Susanna , Drovandi Christopher , Hassan Conor , Jenner Adrianne L. , Mayfield Helen J. , McGree James M. , Mengersen Kerrie , Price Aiden , Salomone Robert , Santos-Fernandez Edgar , Vercelloni Julie , Wang Xiaoyu 
Published: March 2023

Building on a strong foundation of philosophy, theory, methods and computation over the past three decades, Bayesian approaches are now an integral part of the toolkit for most statisticians and data scientists. Whether they are dedicated Bayesians or opportunistic users, applied professionals can now reap many of the benefits afforded by the Bayesian paradigm. In this paper, we touch on six modern opportunities and challenges in applied Bayesian statistics: intelligent data collection, new data sources, federated analysis, inference for implicit models, model transfer and purposeful software products.This article is part of the theme issue ‘Bayesian inference: challenges, perspectives, and prospects’.
Hierarchical Bayesian non-response models for error rates in forensic black-box studies
Authors: Khan Kori , Carriquiry Alicia 
Published: March 2023

Forensic science plays a critical role in the United States criminal legal system. Historically, however, most feature-based fields of forensic science, including firearms examination and latent print analysis, have not been shown to be scientifically valid. Recently, black-box studies have been proposed as a means of assessing whether these feature-based disciplines are valid, at least in terms of accuracy, reproducibility and repeatability. In these studies, forensic examiners frequently either do not respond to every test item or select an answer equivalent to ‘don’t know’. Current black-box studies do not account for these high levels of missingness in statistical analyses. Unfortunately, the authors of black-box studies typically do not share the data necessary to meaningfully adjust estimates for the high proportion of missing responses. Borrowing from work in the context of small area estimation, we propose the use of hierarchical Bayesian models that do not require auxiliary data to adjust for non-response. Using these models, we offer the first formal exploration of the impact that missingness is playing in error rate estimations reported in black-box studies. We show that error rates currently reported as low as 0.4% could actually be at least 8.4% in models accounting for non-response where inconclusive decisions are counted as correct, and over 28% when inconclusives are counted as missing responses. These proposed models are not the answer to the missingness problem in black-box studies. But with the release of auxiliary information, they can be the foundation for new methodologies to adjust for missingness in error rate estimations.This article is part of the theme issue ‘Bayesian inference: challenges, perspectives, and prospects’.
A gene pathogenicity tool ‘GenePy’ identifies missed biallelic diagnoses in the 100,000 Genomes Project
Authors: Seaby Eleanor G. , Leggatt Gary , Cheng Guo , Thomas N. Simon , Ashton James J , Stafford Imogen ,   Genomics England Consortium, Baralle Diana , Rehm Heidi L. , O’Donnell-Luria Anne , Ennis Sarah 
Published: March 2023

AbstractThe 100,000 Genomes Project (100KGP) diagnosed a quarter of recruited affected participants, but 26% of diagnoses were in genes not on the chosen gene panel(s); with many beingde novovariants of high impact. However, assessing biallelic variants without a gene panel is challenging, due to the number of variants requiring scrutiny. We sought to identify potential missed biallelic diagnoses independent of the gene panel applied using GenePy - a whole gene pathogenicity metric.GenePy scores all variants called in a given individual, incorporating allele frequency, zygosity, and a user-defined deleterious metric (CADD v1.6 applied herein). GenePy then combines all variant scores for individual genes, generating an aggregate score per gene, per participant. We calculated GenePy scores for 2862 recessive disease genes in 78,216 individuals in 100KGP. For each gene, we ranked participant GenePy scores for that gene, and scrutinised affected individuals without a diagnosis whose scores ranked amongst the top-5 for each gene. We assessed these participants’ phenotypes for overlap with the disease gene associated phenotype for which they were highly ranked. Where phenotypes overlapped, we extracted rare variants in the gene of interest and applied phase, ClinVar and ACMG classification looking for putative causal biallelic variants.3184 affected individuals without a molecular diagnosis had a top-5 ranked GenePy gene score and 682/3184 (21%) had phenotypes overlapping with one of the top-ranking genes. After removing 13 withdrawn participants, in 122/669 (18%) of the phenotype-matched cases, we identified a putative missed diagnosis in a top-ranked gene supported by phasing, ClinVar and ACMG classification. A further 334/669 (50%) of cases have a possible missed diagnosis but require functional validation. Applying GenePy at scale has identified potential diagnoses for 456/3183 (14%) of undiagnosed participants who had a top-5 ranked GenePy score in a recessive disease gene, whilst adding only 1.2 additional variants (per individual) for assessment.
A dynamical computational model of theta generation in hippocampal circuits to study theta-gamma oscillations during neurostimulation
Authors: Vardalakis Nikolaos , Aussel Amélie , Rougier Nicolas P. , Wagner Fabien B. 
Published: March 2023

AbstractNeurostimulation of the hippocampal formation has shown promising results for modulating memory but the underlying mechanisms remain unclear. In particular, the effects on hippocampal theta-nested gamma oscillations and theta phase reset, which are both crucial for memory processes, are unknown. Moreover, these effects cannot be investigated using current computational models, which consider theta oscillations with a fixed amplitude and phase velocity. Here, we developed a novel computational model that includes the medial septum, represented as a set of abstract Kuramoto oscillators producing a dynamical theta rhythm with phase reset, and the hippocampal formation, composed of biophysically-realistic neurons and able to generate theta-nested gamma oscillations under theta drive. We showed that, for theta inputs just below the threshold to induce self-sustained theta-nested gamma oscillations, a single stimulation pulse could switch the network behavior from non-oscillatory to a state producing sustained oscillations. Next, we demonstrated that, for a weaker theta input, pulse train stimulation at the theta frequency could transiently restore seemingly physiological oscillations. Importantly, the presence of phase reset influenced whether these two effects depended on the phase at which stimulation onset was delivered, which has practical implications for designing neurostimulation protocols that are triggered by the phase of ongoing theta oscillations. This novel model opens new avenues for studying the effects of neurostimulation on the hippocampal formation. Furthermore, our hybrid approach that combines different levels of abstraction could be extended in future work to other neural circuits that produce dynamical brain rhythms.
AI-Designed, Mutation-Resistant Broad Neutralizing Antibodies Against Multiple SARS-CoV-2 Strains
Authors: Kang Yue , Jiao Yang , Jin Kevin , Pan Lurong 
Published: March 2023

AbstractIn this study, we generated a Digital Twin for SARS-CoV-2 by integrating data and meta-data with multiple data types and processing strategies, including machine learning, natural language processing, protein structural modeling, and protein sequence language modeling. This approach enabled the computational design of broadly neutralizing antibodies against over 1300 different historical strains of SARS-COV-2 containing 64 mutations in the receptor binding domain (RBD) region. The AI-designed antibodies were experimentally validated in real-virus neutralization assays against multiple strains including the newer Omicron strains that were not included in the initial design base. Many of these antibodies demonstrate strong binding capability in ELISA assays against the RBD of multiple strains. These results could help shape future therapeutic design for existing strains, as well as predicting hidden patterns in viral evolution that can be learned by AI for developing future antiviral treatments.
Novel Herpesvirus Transcripts with Putative Regulatory Roles in DNA Replication and Global Transcription
Authors: Torma Gábor , Tombácz Dóra , Almsarrhad Islam A.A. , Csabai Zsolt , Nagy Gergely Ármin , Kakuk Balázs , Gulyás Gábor , Spires Lauren McKenzie , Gupta Ishaan , Fülöp Ádám , Dörmő Ákos , Prazsák István , Mizik Máté , Dani Virág Éva , Csányi Viktor , Zádori Zoltán , Toth Zsolt , Boldogkői Zsolt 
Published: March 2023

ABSTRACTIn the last couple of years, the rapid advances and decreasing costs of sequencing technologies have revolutionized transcriptomic research. Long-read sequencing (LRS) techniques are able to detect full-length RNA molecules in a single run without the need for additional assembly steps. LRS studies have revealed an unexpected transcriptomic complexity in a variety of organisms, including viruses. A number of transcripts with proven or putative regulatory role, mapping close to or overlapping the replication origins (Oris) and the nearby transcription activator genes, have been described in herpesviruses. In this study, we applied both newly generated and previously published LRS and short-read sequencing datasets to discover additional Ori-proximal transcripts in nine herpesviruses belonging to all of the three subfamilies (alpha, beta and gamma). We identified novel long non-coding RNAs (lncRNAs), as well as splice and length isoforms of mRNAs and lncRNAs. Furthermore, our analysis disclosed an intricate meshwork of transcriptional overlaps at the examined genomic regions. Our results suggest the existence of a ‘super regulatory center’, which controls both the replication and the global transcription through multilevel interactions between the molecular machineries.