bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated safety analysis of baricitinib in adults with severe alopecia areata from two randomized clinical trials
Authors: King Brett , Mostaghimi Arash , Shimomura Yutaka , Zlotogorski Abraham , Choi Gwang-Seong , Blume-Peytavi Ulrike , Passeron Thierry , Holzwarth Katrin , Dutronc Yves , McCollam Jill , Yang Fan Emily , Stanley Sarah , Wu Wen-Shuo , Sinclair Rodney 
Published: January 2023

Abstract

Background
Baricitinib, an oral, selective, reversible Janus kinase (JAK)1/JAK2 inhibitor, is an approved treatment for adults with severe alopecia areata (AA) in the USA, European Union and Japan.

Objectives
To report safety data for baricitinib in patients with severe AA from two clinical trials including long-term extension periods.

Methods
This analysis includes pooled patient-level safety data from two trials, an adaptive phase II/III trial (BRAVE-AA1) and a phase III trial (BRAVE-AA2) (ClinicalTrials.gov, NCT03570749 and NCT03899259). Data are reported in three datasets: (i) the placebo-controlled dataset (up to week 36): baricitinib 2 mg and 4 mg vs. placebo; (ii) the extended dataset (up to the data cutoff): patients remaining on continuous treatment with baricitinib 2 mg or 4 mg from baseline; and (iii) the all-baricitinib dataset (all-BARI, up to the data cutoff): all patients receiving any dose of baricitinib at any time during the trials. Safety outcomes include treatment-emergent adverse events (TEAEs), adverse events of special interest and abnormal laboratory changes. Proportions of patients with events and incidence rates (IR) were calculated.

Results
Data were collected for 1303 patients who were given baricitinib, reflecting 1868 patient-years of exposure (median 532 days). The most frequently reported TEAEs during the placebo-controlled period (based on the baricitinib 4-mg group) were upper respiratory tract infection, nasopharyngitis, headache, acne and elevated blood creatine phosphokinase (CPK). During the placebo-controlled period, the frequency of acne was higher with baricitinib than placebo, and elevated CPK was higher with baricitinib 4 mg than placebo and baricitinib 2 mg. In all-BARI, the IR of serious infections was low (n = 16, IR 0.8). There was one opportunistic infection (IR 0.1), and 34 cases of herpes zoster (IR 1.8). There was one positively adjudicated major adverse cardiovascular event (myocardial infarction) (IR 0.1), one pulmonary embolism (IR 0.1), three malignancies other than nonmelanoma skin cancer (IR 0.2) and one gastrointestinal perforation (IR 0.1). No deaths were reported.

Conclusions
This integrated safety analysis in patients with severe AA is consistent with the overall safety profile of baricitinib. Some differences with atopic dermatitis were noted that may be attributable to the disease characteristics of AA.
Trends in keratinocyte skin cancer incidence, mortality and burden of disease in 33 countries between 1990 and 2017
Authors: Yang Dorothy D , Borsky Kim , Jani Chinmay , Crowley Conor , Rodrigues Jeremy N , Matin Rubeta N , Marshall Dominic C , Salciccioli Justin D , Shalhoub Joseph , Goodall Richard 
Published: January 2023

Abstract

Background
Keratinocyte cancers (KCs) are the most common type of cancer in the White population worldwide, with associated high healthcare costs. Understanding the epidemiological trends for KCs, namely basal cell carcinomas (BCCs) and cutaneous squamous cell carcinomas (SCCs), is required to assess burden of disease, project future trends and identify strategies for addressing this pressing global health issue.

Objectives
To report trends in BCC and SCC incidence, and SCC mortality and disability-adjusted life-years (DALYs).

Methods
An observational study of the Global Burden of Disease (GBD) database between 1990 and 2017 was performed. European Union countries and other selected high-income countries, including the UK and the USA, classified as having high-quality mortality data, were included. Annual age-standardized incidence rates (ASIRs), age-standardized death rates (ASDRs) and DALYs for each country were obtained from the GBD database. Trends were described using joinpoint regression analysis.

Results
Overall, 33 countries were included. For both BCC and SCC in 2015–2017, the highest ASIRs were observed in the USA and Australia. Males had higher ASIRs than females at the end of the observation period in all countries for SCC, and in all countries but two for BCC. In contrast, the highest ASDRs for SCC were observed in Australia and Latvia for males, and in Romania and Croatia for females. The highest DALYs for SCC for both sexes were seen in Australia and Romania. Over the observation period, there were more countries demonstrating decreasing trends in mortality than in incidence, and disparities were observed between which countries had comparatively high mortality rates and which had high incidence rates. Overall reductions in SCC DALYs were observed in 24 of 33 countries for males, and 25 countries for females.

Conclusions
Over the past 27 years, although trends in SCC incidence have risen in most countries, there is evidence that mortality rates have been decreasing. Burden of disease as assessed using DALYs has decreased in the majority of countries. Future work will explore potential explanatory factors for the observed disparity in trends in SCC incidence and mortality.
Anatomical contacts between sensory neurons and epidermal cells: an unrecognized anatomical network for neuro-immuno-cutaneous crosstalk
Authors: Talagas Matthieu 
Published: January 2023

Abstract
Sensory neurons innervating the skin are conventionally thought to be the sole transducers of touch, temperature, pain and itch. However, recent studies have shown that keratinocytes – like Merkel cells – act as sensory transducers, whether for innocuous or noxious mechanical, thermal or chemical stimuli, and communicate with intraepidermal free nerve endings via chemical synaptic contacts. This paradigm shift leads to consideration of the whole epidermis as a sensory epithelium. Sensory neurons additionally function as an efferent system. Through the release of neuropeptides in intimate neuroepidermal contact areas, they contribute to epidermal homeostasis and to the pathogenesis of inflammatory skin diseases. To counteract the dogma regarding neurocutaneous interactions, seen exclusively from the perspective of soluble and spreading mediators, this review highlights the essential contribution of the unrecognized anatomical contacts between sensory neurons and epidermal cells (keratinocytes, melanocytes, Langerhans cells and Merkel cells), which take part in the reciprocal dialogue between the skin, nervous system and immune system.
Impact of perioperative α1-antagonists on postoperative urinary retention in orthopaedic surgery: meta-analysis
Authors: Huang Yun-Ting , Chang Yu , Kang Yi-No , Huang Chin-Hsuan , Lin Yu-Shiuan , Wu Jeffrey , Chi Kuan-Yu , Chen Wei-Cheng 
Published: January 2023

AbstractBackgroundPostoperative urinary retention (POUR) is a common complication following orthopaedic surgery. Previous studies attempted to establish the preventative role of α1-antagonist in POUR in the general surgical population; however, there is still no consensus regarding its use in orthopaedic surgery due to limited evidence.MethodsElectronic databases of Cochrane Library, Embase, MEDLINE, and ClinicalTrials.gov were searched by two independent investigators from inception to 1 March 2022 to identify relevant randomized clinical trials. Two reviewers independently completed a critical appraisal of included trials by using the Cochrane Risk of Bias tool version 2.0 and extracted data from included articles. Risk of POUR was summarized as risk ratio (RR) with 95 per cent confidence intervals (c.i.). Mean difference (MD) was used for meta-analysis of continuous outcomes.ResultsFive randomized clinical trials involving 878 patients (α1-antagonist, 434; placebo, 444) undergoing hip/knee arthroplasty and spine surgeries were included. One study was assessed as high risk of bias from the randomization process and was excluded from the final meta-analysis. There was no difference in the risk of POUR between patients taking α1-antagonist and the placebo in arthroplasty (RR, 0.64; 95 per cent c.i., 0.36 to 1.14) and in spine surgeries (RR, 1.03; 95 per cent c.i., 0.69 to 1.55). There was no difference in length of stay (MD, −0.14 days; 95 per cent c.i., −0.33 to 0.05). Use of α1-antagonist was associated with a higher risk of adverse events (RR, 1.97; 95 per cent c.i., 1.27 to 3.06), with a composite of dizziness, light-headedness, fatigue, altered mental status, and syncope being the most commonly reported symptoms.ConclusionIn patients undergoing spinal surgery and joint arthroplasty, routine administration of perioperative α1-antagonist does not decrease risk of POUR but does increase perioperative dizziness, light-headedness, and syncope.
Polyploidization was not involved in the origin of five endemic species from southern Europe but is otherwise frequent inEuphorbiasectionEsula(Euphorbiaceae)
Authors: Heimer Valentin , Frajman Božo 
Published: January 2023

AbstractPolyploidization is a key factor in the diversification of flowering plants, but appears to be of only minor importance in the evolution of Euphorbia subgenus Esula. An exception is Euphorbia section Esula, including c. 100 species, many of which are widespread, but several have restricted distribution areas. We used ITS sequencing and relative genome size estimation to explore the evolutionary origin of E. gayi, E. graminifolia, E. tommasiniana, E. valliniana and E. variabilis, which are endemic to disjunct areas along the southern and western margins of the Alps, Corsica and Sardinia. In addition, we explored the incidence of polyploidy across different lineages of E. section Esula. Our phylogenetic results revealed several lineages with unresolved relationships that probably diverged in the Late Miocene, but only one (the Eurasian Group) underwent considerable diversification, probably due to numerous polyploidization events. Several polyploid species or mixed ploidy species in this group are distributed across large areas of Eurasia. All other lineages remained mostly diploid and species-poor, but dispersed to various continents, where most of the species have restricted distribution areas. The five focal species are diploid, but they do not share a common ancestor. Euphorbia graminifolia and E. tommasiniana belong to the Eurasian Group, whereas E. gayi, E. valliniana and E. variabilis belong to the Cosmopolitan Group and are thus not closely related to other European members of the section. Phylogenetic analyses recovered E. valliniana and E. variabilis as genetically distinct, although closely related. This, in combination with a clear morphological differentiation as revealed by morphometric analyses, supports their recognition as independent species. Our study highlights the important role polyploidization had for plant diversification as well as the effects of other factors such as vicariance in disjunct refugia, which probably led to the origin of the five endemic species from Euphorbia section Esula.
Quantitative approaches to guide epilepsy surgery from intracranial EEG
Authors: Bernabei John M , Li Adam , Revell Andrew Y , Smith Rachel J , Gunnarsdottir Kristin M , Ong Ian Z , Davis Kathryn A , Sinha Nishant , Sarma Sridevi , Litt Brian 
Published: January 2023

AbstractOver the past 10 years, the drive to improve outcomes from epilepsy surgery has stimulated widespread interest in methods to quantitatively guide epilepsy surgery from intracranial EEG (iEEG). Many patients fail to achieve seizure freedom, in part due to the challenges in subjective iEEG interpretation. To address this clinical need, quantitative iEEG analytics have been developed using a variety of approaches, spanning studies of seizures, interictal periods, and their transitions, and encompass a range of techniques including electrographic signal analysis, dynamical systems modeling, machine learning and graph theory. Unfortunately, many methods fail to generalize to new data and are sensitive to differences in pathology and electrode placement.Here, we critically review selected literature on computational methods of identifying the epileptogenic zone from iEEG. We highlight shared methodological challenges common to many studies in this field and propose ways that they can be addressed. One fundamental common pitfall is a lack of open-source, high-quality data, which we specifically address by sharing a centralized high-quality, well-annotated, multicentre dataset consisting of &gt;100 patients to support larger and more rigorous studies. Ultimately, we provide a road map to help these tools reach clinical trials and hope to improve the lives of future patients.
Oral ivermectin to treat scabies: a comparison of two different regimens
Authors: Balestri Riccardo , Magnano Michela , Infusino Salvatore Domenico , Girardelli Carlo R , Ioris Tommaso , Rech Giulia 
Published: January 2023

Abstract
As Sarcoptes scabiei is becoming less sensitive to permethrin, clinicians have started to prescribe oral ivermectin (OI) as a first-line treatment. Guidelines suggest OI 200 µg kg–1 as two doses, 1 week apart. However, the black box of the ivermectin registered in Italy recommends a single dose. To compare these two regimens, we collected 71 cases of scabies and treated them according to this protocol [single-dose group (SDG)]. This population was compared to 68 patients who received two doses 1 week apart [double-dose group (DDG)]. Clearance of the disease was achieved in 98% of DDG patients. In the SDG, treatment was successful in only 58% of patients. This study confirms that the absence of a second intake of OI is one of the main predictors of treatment failure (P &lt; 0.001), which may also increase the likelihood of emerging resistance in S. scabiei.
Learning dermatology in medical school: analysis of dermatology topics tested in popular question banks
Authors: Ahmad Maham , Perkins Sara H , Perkins Sara H 
Published: January 2023

Abstract
Given the lack of formal dermatology education in medical schools, dermatology principles covered in board exam preparatory resources remain the only standardized concepts that all medical students across the USA universally learn. The primary objective of this study was to quantify the dermatology topics represented in UWorld and AMBOSS Step 1 and Step 2CK question banks. Our study found that 49% of the 655 questions on dermatology assessed the top 10 most prevalent skin diseases encountered in clinical practice with a variety of rare conditions also tested. Step 2CK question banks had a higher proportion of questions that assessed management of dermatological conditions. Furthermore, there was a large variability in the proportion of questions that included images of the condition. This study highlights the need and opportunity for standardization of dermatology teaching in medical school curricula to optimally prepare graduating physicians for future practice.
Characterizing the burden of calciphylaxis: a qualitative analysis
Authors: Singh Rohan , McCain Sarah , Feldman Steven R , Strowd Lindsay C 
Published: January 2023

Abstract
Calciphylaxis is a debilitating disease associated with high mortality and morbidity secondary to pain, nonhealing wounds and frequent hospital admissions. We qualitatively assessed the burden of calciphylaxis on patient quality of life through semi-structured interviews with nine adult participants. Participants identified an inability to complete activities of daily living because of mobility impairment and decreased strength, although most denied complete dependence on others. All participants described pain as the worst aspect of disease, citing a variable course, unpredictability in severity and poor control despite medical therapy. Calciphylaxis also caused feelings of sadness and anger, having a negative impact on self-confidence. Supportive care needs to address the pervasive and severe nature of pain, mobility impairment and psychiatric comorbidities; such interventions may decrease the overall burden for patients with calciphylaxis.
Switching from adalimumab originator to biosimilar: a 3-year retrospective cohort analysis
Authors: Killion Lisa , Alsharqi Ali , Kirby Brian 
Published: January 2023

Our three year retrospective cohort study demonstrated that the vast majority of patients tolerated the switch from adalimumab originator to adalimumab biosimilar, with a 19% switchback rate. All patients who switched back to originator from biosimilar recovered from loss of efficiency and reported adverse events.
Physicians therefore should be confident in switching patients with well controlled psoriasis to adalimumab biosimilars.
Human B-cell subset identification and changes in inflammatory diseases
Authors: Velounias Rebekah L , Tull Thomas J 
Published: January 2023

Summary
Our understanding of the B-cell subsets found in human blood and their functional significance has advanced greatly in the past decade. This has been aided by the evolution of high dimensional phenotypic tools such as mass cytometry and single-cell RNA sequencing which have revealed heterogeneity in populations that were previously considered homogenous. Despite this, there is still uncertainty and variation between studies as to how B-cell subsets are identified and named. This review will focus on the most commonly encountered subsets of B cells in human blood and will describe gating strategies for their identification by flow and mass cytometry. Important changes to population frequencies and function in common inflammatory and autoimmune diseases will also be described.
Cell-specific switch for epileptiform activity: critical role of interneurons in the mouse subicular network
Authors: Wickham J , Ledri M , Andersson M , Kokaia M 
Published: January 2023

Abstract
During epileptic seizures, neuronal network activity is hyper synchronized whereby GABAergic parvalbumin-interneurons may have a key role. Previous studies have mostly utilized 4-aminopyridine to induce epileptiform discharges in brain slices from healthy animals. However, it is not clear if the seizure-triggering ability of parvalbumin-interneurons also holds true without the use of external convulsive agents. Here, we investigate whether synchronized activation of parvalbumin-interneurons or principal cells can elicit epileptiform discharges in subiculum slices of epileptic mice. We found that selective synchronized activation of parvalbumin-interneurons or principal cells with optogenetics do not result in light-induced epileptiform discharges (LIEDs) neither in epileptic nor in normal brain slices. Adding 4-aminopyridine to slices, activation of parvalbumin-interneurons still failed to trigger LIEDs. In contrast, such activation of principal neurons readily generated LIEDs with features resembling afterdischarges. When GABAA receptor blocker was added to the perfusion medium, the LIEDs were abolished. These results demonstrate that in subiculum, selective synchronized activation of principal excitatory neurons can trigger epileptiform discharges by recruiting a large pool of downstream interneurons. This study also suggests region-specific role of principal neurons and interneurons in ictogenesis, opening towards differential targeting of specific brain areas for future treatment strategies tailored for individual patients with epilepsy.
White-matter degradation and dynamical compensation support age-related functional alterations in human brain
Authors: Petkoski Spase , Ritter Petra , Jirsa Viktor K 
Published: January 2023

Abstract
Structural connectivity of the brain at different ages is analyzed using diffusion-weighted magnetic resonance imaging (MRI) data. The largest decrease of streamlines is found in frontal regions and for long inter-hemispheric links. The average length of the tracts also decreases, but the clustering is unaffected. From functional MRI we identify age-related changes of dynamic functional connectivity (dFC) and spatial covariation features of functional connectivity (FC) links captured by metaconnectivity. They indicate more stable dFC, but wider range and variance of MC, whereas static features of FC did not show any significant differences with age. We implement individual connectivity in whole-brain models and test several hypotheses for the mechanisms of operation among underlying neural system. We demonstrate that age-related functional fingerprints are only supported if the model accounts for: (i) compensation of the individual brains for the overall loss of structural connectivity and (ii) decrease of propagation velocity due to the loss of myelination. We also show that with these 2 conditions, it is sufficient to decompose the time-delays as bimodal distribution that only distinguishes between intra- and inter-hemispheric delays, and that the same working point also captures the static FC the best, and produces the largest variability at slow time-scales.
Novel insights into axon diameter and myelin content in late childhood and adolescence
Authors: Genc Sila , Raven Erika P , Drakesmith Mark , Blakemore Sarah-Jayne , Jones Derek K 
Published: January 2023

AbstractWhite matter microstructural development in late childhood and adolescence is driven predominantly by increasing axon density and myelin thickness. Ex vivo studies suggest that the increase in axon diameter drives developmental increases in axon density observed with pubertal onset. In this cross-sectional study, 50 typically developing participants aged 8–18 years were scanned using an ultra-strong gradient magnetic resonance imaging scanner. Microstructural properties, including apparent axon diameter $({d}_a)$, myelin content, and g-ratio, were estimated in regions of the corpus callosum. We observed age-related differences in ${d}_a$, myelin content, and g-ratio. In early puberty, males had larger ${d}_a$ in the splenium and lower myelin content in the genu and body of the corpus callosum, compared with females. Overall, this work provides novel insights into developmental, pubertal, and cognitive correlates of individual differences in apparent axon diameter and myelin content in the developing human brain.
Brain dynamics in triple-network interactions and its relation to multiple cognitive impairments in mild traumatic brain injury
Authors: Li Xuan , Jia Xiaoyan , Liu Yuling , Bai Guanghui , Pan Yizhen , Ji Qiuyu , Mo Zhaoyi , Zhao Wenpu , Wei Yixin , Wang Shan , Yin Bo , Zhang Jie , Bai Lijun 
Published: January 2023

Abstract
Traumatic brain injury (TBI) disrupt the coordinated activity of triple-network and produce impairments across several cognitive domains. The triple-network model posits a key role of the salience network (SN) that regulates interactions with the central executive network (CEN) and default mode network (DMN). However, the aberrant dynamic interactions among triple-network and associations with neurobehavioral symptoms in mild TBI was still unclear. In present study, we used brain network interaction index (NII) and dynamic functional connectivity to examine the time-varying cross-network interactions among the triple-network in 109 acute patients, 41 chronic patients, and 65 healthy controls. Dynamic cross-network interactions were significantly increased and more variable in mild TBI compared to controls. Crucially, mild TBI exhibited an increased NII as enhanced integrations between the SN and CEN while reduced coupling of the SN with DMN. The increased NII also implied much severer and multiple domains of cognitive impairments at both acute and chronic mild TBI. Abnormities in time-varying engagement of triple-network is a clinically relevant neurobiological signature of psychopathology in mild TBI. The findings provided align with and advance an emerging perspective on the importance of aberrant brain dynamics associated with highly disparate cognitive and behavioral outcomes in trauma.