bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-risk mucosal human papillomavirus-associated squamous cell carcinoma of the fingers presents distinctive clinicopathological characteristics and outcomes: a bicentric retrospective study
Authors: Marti-Marti Ignasi , Bosch-Amate Xavier , Morgado-Carrasco Daniel , Albero-González Raquel , Santos-Briz Angel , Puebla-Tornero Laura , Revelles-Peñas Leonor , Cañueto Javier , Alòs Llúcia , Toll Agustí 
Published: January 2023

Abstract

Background
High-risk mucosal human papillomavirus (HR-HPV) seems to play a role in cutaneous squamous cell carcinoma (cSCC), particularly in nail tumours, where genitodigital transmission has been suggested. The role of HR-HPV in nonungual cSCC of the finger needs to be clarified.

Aim
To evaluate the prevalence, clinicopathological characteristics, surrogates and outcomes of HR-HPV in cSCC of the finger.

Methods
This was an observational bicentric study including patients with an excised in situ or invasive cSCC located on the finger. Differences in HR-HPV and non-HR-HPV tumours were evaluated.

Results
Forty-five patients (45 tumours) were included. HR-HPV was detected in 33% of cases (22% HPV type 16). The mean age was lower in patients with HR-HPV than in those with non-HR-HPV (62·4 vs. 81·1 years, P = 0·001). HR-HPV tumours were smaller (10 mm vs. 15 mm, P = 0·07) and more frequently intraepidermal (60% vs. 20%, P = 0·004). The absence of elastosis (P = 0·030) and inflammation (P = 0·026) and the presence of basaloid morphology (P = 0·003) were surrogates of HR-HPV detection. Mean p16 positivity was 61% in HR-HPV and 36% in non-HR-HPV tumours (P = 0·061). Recurrence after surgery was more common in HR-HPV tumours (58% vs. 34%), although this was not statistically significant. HR-HPV was detected in 27% of the nonungual tumours.

Conclusion
HR-HPV-associated cSCC of the finger appears in younger patients, is smaller and is less infiltrative than non-HR-HPV tumours. The presence of a basaloid morphology and the absence of elastosis and inflammation could be used as markers for HR-HPV detection. The high prevalence of HR-HPV in nonungual cSCC suggests its aetiopathogenic role in these tumours.
The dermatologist identity crisis: a phenomenological analysis of dermatology trainee professional identity during generalist redeployment
Authors: Guckian Jonathan , Lee Natasha , Sutton Jonathan E , Mayat Nabilah Y , Morrison Kirsty , Farquhar Katherine E L , Singh Minal 
Published: January 2023

Abstract

Background
Dermatology faces a workforce crisis against a backdrop of wider medical education shifts towards generalism. A pivot towards generalism may have an impact on dermatology trainee professional identity, which, to our knowledge, has not been investigated and is known to have an impact on competence and conceptualization of ethics among physicians. Disruption because of the COVID-19 pandemic led to dermatology trainee redeployment and therefore presents a unique opportunity to examine dermatology trainee professional identity during times of pressure.

Aim
To identify the impact of COVID-19 redeployment on dermatology trainee professional identity, the factors influencing identity and whether such factors affect trainees’ perceptions about their future careers.

Methods
Ten trainees were purposively recruited to the study. Data were collected through semistructured interviews and were analysed phenomenologically using the template analysis method. Central and integrative themes were identified.

Results
Three central themes were identified: trainee identity and values; redeployment transitions; and future clarity. Three integrative themes were found: tribes; sense of purpose; and uncertainty. Trainees see competence and community as central to the dermatologist identity. Most trainees experienced a reaffirmation of their prior values, psychologically retreating to close-knit communities. However, some underwent disorienting dilemmas, later reflecting on their futures as dermatologists.

Conclusion
Healthcare crises may have a significant impact on dermatology trainee professional identity and may lead to reaffirmation of prior tribal values or disorienting reflection upon future career trajectories. Improved support among diverse communities, minimization of uncertainty and fostering a sense of purpose among trainees may aid identity enrichment and safeguard the future dermatology consultant workforce.
A review of topical probiotic therapy for atopic dermatitis
Authors: Herbert Samantha , Haughton Reneé , Nava Jordan , Ji-Xu Antonio , Le Stephanie T , Maverakis Emanual 
Published: January 2023

Abstract
Atopic dermatitis (AD) is a common, chronic skin disorder that is associated with dysbiosis of the skin microbiome along with an impaired skin barrier and abnormal immune signalling. Particularly, AD has been associated with increased abundance of Staphylococcus aureus and decreased overall bacterial diversity. Topical probiotic formulations are garnering further interest in the treatment of AD and may be derived from commensal bacteria found on healthy epithelium or from exogenous bacteria. Strains chosen for clinical trials have often demonstrated antimicrobial actions to S. aureus in vitro. Multiple randomized clinical trials with topical probiotics have resulted in significant improvements in clinical severity, decreased abundance of S. aureus in treated lesional skin and increased bacterial diversity. Side-effects from available studies have been minimal apart from one patient who developed a furuncle in the treatment area. Topical probiotics have been shown to be safe and potentially efficacious in AD; however, further research including larger, longer-term clinical trials need to be performed before topical probiotics should be recommended to patients.
Bedbugs: how to diagnose and manage cases of infestations
Authors: Shipman Kate E , Weaving Gary , Shipman Alexa R 
Published: January 2023

AbstractBedbugs are on the rise in urban populations across the world, perhaps reflecting the ban on the use of organophosphates in many countries worldwide. They are flat obligate haematophagous insects, preferring humans, and as a consequence the bedbug bites lack toxins and can often go unnoticed for some time. Bites can, however, cause weals, purpura, petechiae, vesicles, pustules, papular urticaria, localized infection and rarely anaphylaxis. Infestations have to be confirmed by finding the bugs, usually around the bed of the person being bitten. Eradication usually requires a combination of physical (for example high temperature, mattresses protectors, traps, cold) and chemical methods (for example chrysanthemic acid derivatives plus potentiators such as geraniol and piperonyl butoxide or acetylcholine esterase inhibitors).
Connectome-based predictive modeling predicts paranoid ideation in young men with paranoid personality disorder: a resting-state functional magnetic resonance imaging study
Authors: Zhang Die , Yu Lan , Chen Yingying , Shen Jing , Du Lina , Lin Lin , Wu Jianlin 
Published: January 2023

Abstract
Paranoid personality disorder (PPD), a mental disorder that affects interpersonal relationships and work, is frequently neglected during diagnosis and evaluation at the individual-level. This preliminary study aimed to investigate whether connectome-based predictive modeling (CPM) can predict paranoia scores of young men with PPD using whole-brain resting-state functional connectivity (rs-FC). College students with paranoid tendencies were screened using paranoia scores ≥60 derived from the Minnesota Multiphasic Personality Inventory; 18 participants were ultimately diagnosed with PPD according to the Diagnostic and Statistical Manual of Mental Disorders and subsequently underwent resting-state functional magnetic resonance imaging. Whole-brain rs-FC was constructed, and the ability of this rs-FC to predict paranoia scores was evaluated using CPM. The significance of the models was assessed using permutation tests. The model constructed based on the negative prediction network involving the limbic system-temporal lobe was observed to have significant predictive ability for paranoia scores, whereas the model constructed using the positive and combined prediction network had no significant predictive ability. In conclusion, using CPM, whole-brain rs-FC predicted the paranoia score of patients with PPD. The limbic system-temporal lobe FC pattern is expected to become an important neurological marker for evaluating paranoid ideation.
Long-Acting Cabotegravir and Rilpivirine Dosed Every 2 Months in Adults With Human Immunodeficiency Virus 1 Type 1 Infection: 152-Week Results From ATLAS-2M, a Randomized, Open-Label, Phase 3b, Noninferiority Study
Authors: Overton Edgar T , Richmond Gary , Rizzardini Giuliano , Thalme Anders , Girard Pierre-Marie , Wong Alexander , Porteiro Norma , Swindells Susan , Reynes Jacques , Noe Sebastian , Harrington Conn , Español Carlos Martín , Acuipil Carolina , Aksar Asma , Wang Yuanyuan , Ford Susan L , Crauwels Herta , van Eygen Veerle , Van Solingen-Ristea Rodica , Latham Christine L , Thiagarajah Shanker , D’Amico Ronald , Smith Kimberly Y , Vandermeulen Kati , Spreen William R 
Published: January 2023

Abstract

Background
Cabotegravir (CAB) + rilpivirine (RPV) dosed intramuscularly monthly or every 2 months is a complete, long-acting (LA) regimen for the maintenance of HIV-1 virologic suppression. Here, we report the antiretroviral therapy as long acting suppression (ATLAS)-2M study week 152 results.

Methods
ATLAS-2M is a phase 3b, randomized, multicenter study assessing the efficacy and safety of CAB+RPV LA every 8 weeks (Q8W) versus every 4 weeks (Q4W). Virologically suppressed (HIV-1 RNA &lt;50 copies/mL) individuals were randomized to receive CAB+RPV LA Q8W or Q4W. Endpoints included the proportion of participants with plasma HIV-1 RNA ≥50 copies/mL and &lt;50 copies/mL, incidence of confirmed virologic failure (CVF; 2 consecutive measurements ≥200 copies/mL), safety, and tolerability.

Results
A total of 1045 participants received CAB+RPV LA (Q8W, n = 522; Q4W, n = 523). CAB+RPV LA Q8W demonstrated noninferior efficacy versus Q4W dosing, with 2.7% (n = 14) and 1.0% (n = 5) of participants having HIV-1 RNA ≥50 copies/mL, respectively, with adjusted treatment difference being 1.7% (95% CI: 0.1–3.3%), meeting the 4% noninferiority threshold. At week 152, 87% of participants maintained HIV-1 RNA &lt;50 copies/mL (Q8W, 87% [n = 456]; Q4W, 86% [n = 449]). Overall, 12 (2.3%) participants in the Q8W arm and 2 (0.4%) in the Q4W arm had CVF. Eight and 10 participants with CVF had treatment-emergent, resistance-associated mutations to RPV and integrase inhibitors, respectively. Safety profiles were comparable, with no new safety signals observed since week 48.

Conclusions
These data demonstrate virologic suppression durability with CAB+RPV LA Q8W or Q4W for ∼3 years and confirm long-term efficacy, safety, and tolerability of CAB+RPV LA as a complete regimen to maintain HIV-1 virologic suppression.
A Model-Based Tool for Guiding Infliximab Induction Dosing to Maximize Long-term Deep Remission in Children with Inflammatory Bowel Diseases
Authors: Kantasiripitak Wannee , Wicha Sebastian G , Thomas Debby , Hoffman Ilse , Ferrante Marc , Vermeire Séverine , van Hoeve Karen , Dreesen Erwin 
Published: January 2023

Abstract

Background and Aims
Adequate infliximab concentrations during induction treatment are predictive for deep remission [corticosteroid-free clinical and endoscopic remission] at 6 months in children with inflammatory bowel diseases [IBD]. Under standard infliximab induction dosing, children often have low infliximab trough concentrations. Model-informed precision dosing [MIPD; i.e. model-based therapeutic drug monitoring] is advocated as a promising infliximab dosing strategy. We aimed to develop and validate an MIPD framework for guiding paediatric infliximab induction treatment.

Methods
Data from 31 children with IBD [4–18 years] receiving standard infliximab induction dosing (5 mg/kg at week [w]0, w2 and w6) were repurposed. Eight paediatric population pharmacokinetic models were evaluated. Modelling and simulation were used to identify exposure targets, identify an optimal sampling strategy, and develop a multi-model prediction algorithm for implementation into an MIPD software tool. A role for infliximab clearance monitoring was evaluated.

Results
A 7.5 mg/L infliximab concentration target at w12 was associated with 64% probability of deep remission at 6 months. With standard dosing, less than 80% of simulated children &lt;40 kg attained this target. The w12 target was most accurately and precisely achieved by implementing MIPD at w6 using the w6 infliximab concentration [rapid assay required]. The multi-model algorithm outperformed single models when optimizing the w6 dose based on both w2 and w4 concentrations. MIPD using only the w2 concentration resulted in biased and imprecise predictions. Infliximab clearances at w6 and w12 were predictive for deep remission.

Conclusions
A freely available, multi-model MIPD tool facilitates infliximab induction dosing and improves deep remission rates in children with IBD.
Transcatheter versus surgical aortic valve replacement in lower-risk and higher-risk patients: a meta-analysis of randomized trials
Authors: Ahmad Yousif , Howard James P , Arnold Ahran D , Madhavan Mahesh V , Cook Christopher M , Alu Maria , Mack Michael J , Reardon Michael J , Thourani Vinod H , Kapadia Samir , Thyregod Hans Gustav Hørsted , Sondergaard Lars , Jørgensen Troels Højsgaard , Toff William D , Van Mieghem Nicolas M , Makkar Raj R , Forrest John K , Leon Martin B 
Published: January 2023

AbstractAimsAdditional randomized clinical trial (RCT) data comparing transcatheter aortic valve implantation (TAVI) with surgical aortic valve replacement (SAVR) is available, including longer term follow-up. A meta-analysis comparing TAVI to SAVR was performed. A pragmatic risk classification was applied, partitioning lower-risk and higher-risk patients.Methods and resultsThe main endpoints were death, strokes, and the composite of death or disabling stroke, occurring at 1 year (early) or after 1 year (later). A random-effects meta-analysis was performed. Eight RCTs with 8698 patients were included. In lower-risk patients, at 1 year, the risk of death was lower after TAVI compared with SAVR [relative risk (RR) 0.67; 95% confidence interval (CI) 0.47 to 0.96, P = 0.031], as was death or disabling stroke (RR 0.68; 95% CI 0.50 to 0.92, P = 0.014). There were no differences in strokes. After 1 year, in lower-risk patients, there were no significant differences in all main outcomes. In higher-risk patients, there were no significant differences in main outcomes. New-onset atrial fibrillation, major bleeding, and acute kidney injury occurred less after TAVI; new pacemakers, vascular complications, and paravalvular leak occurred more after TAVI.ConclusionIn lower-risk patients, there was an early mortality reduction with TAVI, but no differences after later follow-up. There was also an early reduction in the composite of death or disabling stroke, with no difference at later follow-up. There were no significant differences for higher-risk patients. Informed therapy decisions may be more dependent on the temporality of events or secondary endpoints than the long-term occurrence of main clinical outcomes.
Lifestyle habits associated with cardiac conduction disease
Authors: Frimodt-Møller Emilie K , Soliman Elsayed Z , Kizer Jorge R , Vittinghoff Eric , Psaty Bruce M , Biering-Sørensen Tor , Gottdiener John S , Marcus Gregory M 
Published: January 2023

Abstract

Aims
Cardiac conduction disease can lead to syncope, heart failure, and death. The only available therapy is pacemaker implantation, with no established prevention strategies. Research to identify modifiable risk factors has been scant.

Methods and results
Data from the Cardiovascular Health Study, a population-based cohort study of adults ≥ 65 years with annual 12-lead electrocardiograms obtained over 10 years, were utilized to examine relationships between baseline characteristics, including lifestyle habits, and conduction disease. Of 5050 participants (mean age 73 ± 6 years; 52% women), prevalent conduction disease included 257 with first-degree atrioventricular block, 99 with left anterior fascicular block, 9 with left posterior fascicular block, 193 with right bundle branch block (BBB), 76 with left BBB, and 102 with intraventricular block at baseline. After multivariable adjustment, older age, male sex, a larger body mass index, hypertension, and coronary heart disease were associated with a higher prevalence of conduction disease, whereas White race and more physical activity were associated with a lower prevalence. Over a median follow-up on 7 (interquartile range 1–9) years, 1036 developed incident conduction disease. Older age, male sex, a larger BMI, and diabetes were each associated with incident conduction disease. Of lifestyle habits, more physical activity (hazard ratio 0.91, 95% confidence interval 0.84–0.98, P = 0.017) was associated with a reduced risk, while smoking and alcohol did not exhibit a significant association.

Conclusion
While some difficult to control comorbidities were associated with conduction disease as expected, a readily modifiable lifestyle factor, physical activity, was associated with a lower risk.
Sortilin enhances fibrosis and calcification in aortic valve disease by inducing interstitial cell heterogeneity
Authors: Iqbal Farwah , Schlotter Florian , Becker-Greene Dakota , Lupieri Adrien , Goettsch Claudia , Hutcheson Joshua D , Rogers Maximillian A , Itoh Shinsuke , Halu Arda , Lee Lang Ho , Blaser Mark C , Mlynarchik Andrew K , Hagita Sumihiko , Kuraoka Shiori , Chen Hao Yu , Engert James C , Passos Livia S A , Jha Prabhash K , Osborn Eric A , Jaffer Farouc A , Body Simon C , Robson Simon C , Thanassoulis George , Aikawa Masanori , Singh Sasha A , Sonawane Abhijeet R , Aikawa Elena 
Published: January 2023

AbstractAimsCalcific aortic valve disease (CAVD) is the most common valve disease, which consists of a chronic interplay of inflammation, fibrosis, and calcification. In this study, sortilin (SORT1) was identified as a novel key player in the pathophysiology of CAVD, and its role in the transformation of valvular interstitial cells (VICs) into pathological phenotypes is explored.Methods and resultsAn aortic valve (AV) wire injury (AVWI) mouse model with sortilin deficiency was used to determine the effects of sortilin on AV stenosis, fibrosis, and calcification. In vitro experiments employed human primary VICs cultured in osteogenic conditions for 7, 14, and 21 days; and processed for imaging, proteomics, and transcriptomics including single-cell RNA-sequencing (scRNA-seq). The AVWI mouse model showed reduced AV fibrosis, calcification, and stenosis in sortilin-deficient mice vs. littermate controls. Protein studies identified the transition of human VICs into a myofibroblast-like phenotype mediated by sortilin. Sortilin loss-of-function decreased in vitro VIC calcification. ScRNA-seq identified 12 differentially expressed cell clusters in human VIC samples, where a novel combined inflammatory myofibroblastic-osteogenic VIC (IMO-VIC) phenotype was detected with increased expression of SORT1, COL1A1, WNT5A, IL-6, and serum amyloid A1. VICs sequenced with sortilin deficiency showed decreased IMO-VIC phenotype.ConclusionSortilin promotes CAVD by mediating valvular fibrosis and calcification, and a newly identified phenotype (IMO-VIC). This is the first study to examine the role of sortilin in valvular calcification and it may render it a therapeutic target to inhibit IMO-VIC emergence by simultaneously reducing inflammation, fibrosis, and calcification, the three key pathological processes underlying CAVD.
Evaluation of Associations of Growth Differentiation Factor-11, Growth Differentiation Factor-8, and Their Binding Proteins Follistatin and Follistatin-Like Protein-3 With Dementia and Cognition
Authors: Newman Anne B , Patel Sheena , Kizer Jorge R , Lee Se-Jin , Bhasin Shalinder , Cawthon Peggy , LeBrasseur Nathan , Tracy Russel P , Ganz Peter , Cummings Steven R 
Published: January 2023

Abstract

Background
Studies using heterochronic parabiosis discovered that circulating factors mediate brain aging in animal models.

Methods
We assessed growth differentiation factors (GDF)-11 and GDF-8 using mass spectrometry and inhibitors follistatin and follistatin-like protein-3 (FSTL-3) with ELISA in the Cardiovascular Health Study (CHS; N = 1 506) and the Health, Aging and Body Composition (Health ABC) Study (N = 1 237). CLL-11 and beta-2 microglobulin (β2M) were measured with ELISA in a subset of 400 individuals in Health ABC. Associations were assessed with cognitive function, brain magnetic resonance imaging (MRI) findings (CHS only), and incident dementia using correlations, linear regression, and Cox proportional hazards models.

Results
In CHS, levels of GDF-11, GDF-8, and follistatin were not correlated cross-sectionally with the 3MSE or DSST, brain MRI findings of white matter hyperintensity, atrophy, or small infarcts, nor were they associated with incident dementia. FSTL-3 was modestly correlated with poorer cognitive function, greater white matter hyperintensities, and atrophy on MRI, as well as with incident dementia with an adjusted hazard ratio (HR) of 1.72 (95% CI = 1.13, 2.61) per doubling of FSTL-3. FSTL-3 was not associated with cognition or dementia in Health ABC, but GDF-8 was associated with both. The adjusted HR for incident dementia was 1.50 (95% CI = 1.07, 2.10) per doubling of GDF-8.

Conclusions
Total GDF-11 level was not related to cognition or dementia in older adults. Associations of GDF-8 with cognitive outcomes in Health ABC were not expected, but consistent with animal models. Associations of FSTL-3 with cognition, brain abnormalities, and incident dementia in CHS implicate TGFβ superfamily inhibition in the pathogenesis of dementia.
Everyday Discrimination, Neighborhood Perceptions, and Incidence of Activity Limitations Among Middle-Aged and Older African Americans
Authors: Qin Weidi , Nguyen Ann W , Wang Yi , Hamler Tyrone C , Wang Fei 
Published: January 2023

AbstractObjectivesThis study aims to examine the relationship between everyday discrimination, neighborhood perceptions, and the incidence of daily activity limitations (i.e., activities of daily living [ADL] and instrumental activities of daily living [IADL]) among middle-aged and older African Americans. This study also examines whether neighborhood perceptions moderate the association between discrimination and the incidence of daily activity limitations.MethodsData were from the 2006 to 2016 waves of the Health and Retirement Study. African Americans aged 50 or older free of ADL limitations (N = 1,934) and IADL limitations (N = 2,007) at baseline were selected. Cox proportional hazards regression models were performed to test the study aims. Multiple imputations were applied to handle missing data.ResultsOne-unit increase in everyday discrimination was associated with a 25% (p &lt; .05) higher risk of ADL limitation onset. Perceived neighborhood social cohesion and physical disadvantage moderated the association between discrimination and IADL limitation onset.DiscussionEveryday discrimination represents a significant stressor that negatively affects older African Americans’ performance of daily activities. Community-level efforts that improve neighborhood perceptions are needed to alleviate the negative effects of discrimination on the incidence of activity limitations.