Absolute Area Research Articles

P63 Effectiveness of biologics in clinical practice: Month 12 absolute psoriasis area and severity index outcomes from an international observational Psoriasis Study of Health Outcomes

Abstract Introduction Absolute psoriasis area and severity index (PASI) may be an alternative to relative PASI for treatment comparisons because it reflects both clinically meaningful improvements in disease activity and informs treatment decisions based on actual disease severity, regardless of baseline score. The Psoriasis Study of Health Outcomes (PSoHO) is a 3-year, international, prospective, non-interventional study comparing the effectiveness of anti-IL-17A biologics [ixekizumab (IXE) and secukinumab (SEC)] to other approved biologics in patients with moderate-to-severe psoriasis (PsO) undergoing routine medical care. While relative PASI effectiveness has been reported at 12 months, absolute PASI responses have not yet been shown. This analysis aims to report the effectiveness measured by absolute PASI through 12 months. Methods PSoHO included patients with moderate-to-severe plaque PsO, initiating or switching to a new approved biologic treatment (including biosimilars). This analysis reports the percentage of patients receiving EMA-approved on-label dosing (n = 1678), who achieved absolute PASI scores ≤1, ≤2 and ≤3 at Months 6 and 12. Unadjusted response rates for absolute PASI scores are reported as percentages for each outcome and time point. Non-responder imputation (NRI) was used for missing outcomes and reported here. Results At Month 6, higher response rates for absolute PASI ≤1, ≤2 and ≤3 were achieved by 62.2, 72.1 and 77.8% of patients in the anti-IL-17A cohort compared with 47.4, 61.3 and 69.7% of patients in the other biologics cohort respectively. At Month 12, higher response rates for absolute PASI ≤1, ≤2 and ≤3 were achieved by 56.5, 66.2 and 71.2% of patients in the anti-IL-17A cohort compared with 50.3, 62.6 and 69.0% in the other biologics cohort respectively. At Month 6, across individual treatments, IXE provided the highest response rates in absolute PASI ≤1, ≤2 and ≤3 with 65.2, 74.0 and 79.2%, respectively. At Month 12, IXE showed the highest response rates in absolute PASI ≤1 with 59.6%, followed by risankizumab, guselkumab, tildrakizumab, secukinumab, brodalumab, adalimumab, and ustekinumab with 57.5, 51.5, 51.2, 50.0, 46.7, 44.8, and 42.4% respectively. Conclusion This analysis indicates that the anti-IL-17A cohort of the EMA-approved on-label population had a higher response rate in absolute PASI through Month 12, in a real-world setting. Across individual drug treatments, IXE indicated the highest percentage of patients achieving key endpoints at both 6 and 12 months.

Features of gas chromatographic analysis of thermally unstable compounds

Confirming the stability of analytes during gas chromatographic (GC) analysis is an important criterion, especially for previously uncharacterized compounds. However, the variations of absolute peak areas at different injector temperatures usually do not allow us to reveal the thermal instability of analytes during GC analysis. Such variations may be caused by peak area known discrimination typical for using capillary columns, especially at low split injection. The thermal instability can be revealed only when using relative peak areas.The dependences of the relative peak areas of unstable analytes on the injector temperature (descending), as well as similar dependences for products of their decomposition (ascending), are characterized by the existence of two limits. Low-temperature limits correspond to the initial quantities of unstable analytes, and high-temperature limits, to their complete transformations. Such dependences can be approximated with an equation of logistic regression (synonymous: sigmoid or Boltzmann approximation).The relationships and features of gas chromatographic analysis of thermally unstable compounds are considered with products of free-radical isopropylbenzene (cumene) chlorination and with solutions of ethyl diazoacetate in different solvents as examples. The major cumene chlorination product, (1-chloro-1-methylethyl)benzene, undergoes dehydrochlorination at injector temperatures above 200 °С to form a single product, α-methylstyrene. The analysis of the ethyl diazoacetate solutions is accompanied by the formation of ethyl alkoxyacetates, products of the insertion of intermediate ethoxycarbonylcarbene into OH bonds of alcohols, if they are used as solvents. Comparing the temperatures of half-conversion of the initial ester, T(50 %), and half-formation of the products shows that they are equal to each other. This confirms both the process mechanism and the correctness of the data approximation.

Secukinumab Reduces Psoriasis-associated Pruritus and Regenerates the Cutaneous Nerve Architecture: Results from PSORITUS a Doubleblind, Placebo-controlled, Randomized Withdrawal Phase IIIb Study.

The occurrence of pruritus in psoriasis was previously underestimated but is a significant burden. Secukinumab (SEC), a monoclonal anti-interleukin-17A antibody, efficiently controls signs of psoriasis, but the effect on pruritus and cutaneous neuroanatomy remained unknown. The primary objective of this study (NCT02362789) was to evaluate the superiority of SEC treatment vs placebo on pruritus intensity (visual analogue scale; VAS). Furthermore, the treatment-dependent course of pruritus in association with absolute Psoriasis Area Severity Index (PASI) score, as well as cutaneous histopathology and neuroanatomy, was assessed. Open-label SEC 300 mg s.c. was administered regularly until week 16. Patients who reached a ≥ 98% PASI reduction (PASI ≥ 98) were randomized to receive either placebo or SEC up to week 32. Punch biopsies were collected from lesional psoriatic (baseline, weeks 16 and 32) and non-lesional (baseline) skin for histopathological and neuroanatomical analyses. VAS scores improved significantly after open-label SEC treatment but relapsed upon placebo (29.92 ± 33.8) compared with SEC (12.30 ± 22.6; p = 0.036). After SEC-dependent improvement in PASI, histopathology, marker expression and neuroanatomy, relapse was observed with treatment discontinuation in all parameters except neuroanatomy. SEC was superior to placebo by efficiently controlling reduced pruritus intensity, clinically normalizing skin lesions, and reversing histopathological abnormalities. The neuroanatomy recovered upon SEC and remained stable even after withdrawal.

Quantitative assessments of white matter hyperintensities and plasma biomarkers can predict cognitive impairment and cerebral microbleeds in cerebral small vessel disease patients

The objective of this study is to examine the efficacy of magnetic resonance imaging (MRI) features and peripheral blood biomarkers in assessing cognitive function in patients with cerebral small vessel disease (CSVD). A total of 58 CSVD patients were recruited. Six features of white matter hyperintensities (WMHs) were derived from MRI scans. Additionally, five neurodegenerative biomarkers (Aβ40, Aβ42, t-tau, p-tau181, NfL) and 13 serum inflammatory cytokines (VILIP-1, CCL2, IL-6, IL-18, TNF-α, CX3CL, sTREM-1/2, VEGF, s-RAGE, BNDF, TGF-β1, β-NGF) were quantified. Cognitive assessments were conducted using standardized neuropsychological scales. Spearman analysis revealed that the volumetric characteristics (absolute area, upper area, bottom area, absolute area percentage, upper percentage, and bottom percentage) of WMHs were negatively correlated with performance on all cognitive scale measures except the verbal fluency test (VFT) (r < -0.3, p > 0.05), while they were positively correlated with plasma neurofilament light (NFL) levels (r > 0.4, p < 0.05). Additionally, serum tumor necrosis factor-α (TNF-α) and soluble receptor for advanced glycation end-products (s-RAGE) showed significant correlations with scales of speech function. An integrated model incorporating WMHs features, neurodegenerative biomarkers, and neuroinflammatory markers was developed, demonstrating high predictive accuracy for cognitive impairment with an area under the curve (AUC) of 0.95 (accuracy 0.88, sensitivity 0.87, specificity 0.89). Another integrated model that includes features of WMHs and inflammatory cytokines for predicting cerebral microbleeds (CMBs) achieved an AUC of 0.95 (accuracy 0.88, sensitivity 0.82, specificity 0.92). Our findings suggest that these markers have the potential to be used for the early detection of cognitive decline and CMBs in patients with CSVD.

Unveiling a hide side of the athlete's heart: a CMR focus on the left atrium.

Abstract Background cardiac magnetic resonance (CMR) is the gold standard to evaluate cardiac chambers’ dimensions and function, but data on left atrium (LA) dimensions and function among elite athletes are lacking. Objective to describe LA size and function among a cohort of elite athletes and evaluate eventual differences based on sports discipline and gender. Methods We enrolled 120 Olympic athletes with un-remarkable cardiovascular pre-participation screening tests (mean age 25±5 years, 50% males, 25% skill, 25% power, 25% mixed, 25% endurance). All the athletes underwent CMR without contrast administration. LA dimensions, in terms of absolute and indexed area and volume, were computed using 4- and 2-chamber steady state precession cine-sequences. LA ejection fraction (LAEF) and LA coupling index (LACI index, as the ratio between LA and LV end-diastolic volumes) were calculated. Cine-images were also used to analyse atrial deformation with a dedicated offline software to measure LA global longitudinal strain. LA dimensions and function were compared between males and females and athletes of different sports categories based on European classification. Results Among the entire cohort, endurance athletes showed the greatest remodelling in terms of LA and LV dimensions (Table). There were no significant differences in LAEF and LV-EF between athletes of different sport categories (p=0.121 and p=0.679). A trend in increasing LA volumes and decreasing LA strain consistent with a growing cardiovascular demand was observed, but the only statistically significant difference was between skill athletes and all the other groups for LA volumes (p&amp;lt;0.001), while there were no significant differences in LA strain (p=0.170). LACI did not differ between athletes of different sports categories (p=0.170). Female athletes showed higher LAEF and LA strain than males (respectively 55±5 vs 52±6% p=0.012 and 35±7 vs 32±7%, p=0.009) while LACI did not differ based on gender (19±5% for both females and males, p=0.385). Conclusion Among our cohort of Olympics, LA remodelling was observed in all athletes, being less evident in skill group, as for the LV. Thus, the ratio between LA and LV did not differ between sport categories. LAEF and LA strain were not significantly different between athletes of different sports categories although LA strain was slightly lower in endurance. Female athletes showed higher LAEF and LA strain than males, while LACI was not different based on gender.

The aortic paradox: a nationwide analysis of 523,994 individual echocardiograms exploring aortic dissection

Abstract Background Increasing aortic dilation increases risk of aortic dissection. Nevertheless, dissection occurs below guideline-directed cut-offs for prophylactic surgery. There is no current large-scale population imaging data assessing aortic dimensions before dissection. Purpose To examine the proportion of aortic dissections occurring in people with aortic diameters below guidelines for prophylactic intervention. Methods Patients within the National Echo Database of Australia (NEDA) were stratified according to absolute, height-indexed and body surface area (BSA)-indexed aortic dimensions. Fatal thoracic aortic dissections (ICD-10-AM code I79) were identified via linkage with the National Death Index. Results 524,994 individuals were assessed, comprising patients with normal aortic dimensions (n=460,992), mild dilation (n=53,402), moderate dilation (n=10,029) and severe dilation (n=572). 274,992 (52.4%) were male, with median age 64 years and median follow-up time 6.9 years. 899 fatal aortic dissections occurred (normal diameter=610, mildly-dilated aorta=215, moderately-dilated =53 and severely-dilated=21). Using normal aortas as the reference population, odds of fatal dissection increased with aortic diameter (mild=OR 3.05, 95% confidence interval (CI) 2.61-3.56; moderate=OR 4.0, 95% CI 3.02-5.30; severe=OR 28.72, 95% CI 18.44-44.72). Due to the much larger number of patients without severe aortic dilation, 97.7% of fatal aortic dissections occurred in non-severely dilated aortas. Following sensitivity analysis, severe aortic dilation was responsible for at most 24.4% of fatal aortic dissections. Results were robust for absolute, height-indexed or BSA-indexed aortic measurements. Conclusion Although severe aortic dilatation is associated with a thirty-fold increase in fatal dissection, severely dilated aortas are implicated in only 2.3-24.4% of fatal dissections. This highlights the ‘aortic paradox’ and limitations of current guidelines. Future studies should seek to refine risk predictors in patients without severe aortic dilation.

Does Local Area Social Mobility Affect Political Alienation?

While existing research has considered how individual-level social mobility experiences affect a person’s political outlook, less attention has been paid to how historic levels of social mobility in local areas influence political attitudes and political behaviour. We link individual-level data from the UK Household Longitudinal Study to small area estimates of social class mobility derived from the decennial census. We find that living in a low absolute social mobility area was associated with a higher probability of voting ‘Leave’ in the 2016 UK European Union membership referendum. However, we find no evidence that historical social mobility rates in the local area predict abstention in general elections or attitudinal indicators of political alienation. Given declining rates of upwards mobility, and increasing levels of downwards mobility, our results have important implications for understanding geographies of political discontent.

Residual disease is the main, but not the only factor impacting satisfaction in psoriatic patients undergoing biological therapies.

Despite advancements in psoriasis treatment, a gap remains in aligning patient satisfaction with clinical outcomes. Our study aimed to evaluate which clinical and psychological factors may impact treatment satisfaction in psoriatic patients undergoing long-term biological therapies. We performed an observational, cross-sectional, single-center study involving adult patients with moderate-to-severe psoriasis treated with biologics for at least 12 months. We collected sociodemographic characteristics and data on the course of the psoriasis. We also assessed the absolute (residual) Psoriasis Area and Severity Index (PASI), the site of the residual disease, and the severity of pruritus through the Visual Analogue Scale (VAS). Satisfaction was evaluated using the Treatment Satisfaction Questionnaire for Medication (TSQMv.II). The Type D Personality Scale (DS14 questionnaire and Patient Health Questionnaire-9 assessed the psychological profile. Overall, 146 patients were included, and 82.1% were globally satisfied (global satisfaction TSQM score >75). Linear regression analysis showed a negative correlation between global satisfaction scoring and residual PASI. The multivariable analysis found a higher VAS-pruritus score (OR = 1.20, 95% CI = 1.01-1.44; P = 0.043) and not reaching a residual PASI < 2 (OR = 0.30, 95% CI = 0.09-0.94, P = 0.039) as the strongest predictors of global unsatisfied patients (TSQM < 75%). Other factors unrelated to residual disease, such as gender, class of biologic agent, and type D personality, have also been found to impact patient satisfaction. Our study's findings underscore the complexity of patient satisfaction in psoriasis management and highlight the multifactorial nature of treatment success beyond traditional clinical measures.

Deep Learning Method Applied to Autonomous Image Diagnosis for Prick Test.

The skin prick test (SPT) is used to diagnose sensitization to antigens. This study proposes a deep learning approach to infer wheal dimensions, aiming to reduce dependence on human interpretation. A dataset of SPT images (n = 5844) was used to infer a convolutional neural network for wheal segmentation (ML model). Three methods for inferring wheal dimensions were evaluated: the ML model; the standard protocol (MA1); and approximation of the area as an ellipse using diameters measured by an allergist (MA2). The results were compared with assisted image segmentation (AIS), the most accurate method. Bland-Altman analysis, distribution analyses, and correlation tests were applied to compare the methods. This study also compared the percentage deviation among these methods in determining the area of wheals with regular geometric shapes (n = 150) and with irregular shapes (n = 150). The Bland-Altman analysis showed that the difference between methods was not correlated with the absolute area. The ML model achieved a segmentation accuracy of 85.88% and a strong correlation with the AIS method (ρ = 0.88), outperforming all other methods. Additionally, MA1 showed significant error (13.44 ± 13.95%) for pseudopods. The ML protocol can potentially automate the reading of SPT, offering greater accuracy than the standard protocol.

The Kunming-Montreal Global Biodiversity Framework needs headline indicators that can actually monitor forest integrity

Abstract Intact native forests under negligible large-scale human pressures (i.e. high-integrity forests) are critical for biodiversity conservation. However, high-integrity forests are declining worldwide due to deforestation and forest degradation. Recognizing the importance of high-integrity ecosystems (including forests), the Kunming-Montreal Global Biodiversity Framework (GBF) has directly included the maintenance and restoration of ecosystem integrity, in addition to ecosystem extent, in its goals and targets. Yet, the headline indicators identified to help nations monitor forest ecosystems and their integrity can currently track changes only in (1) forest cover or extent, and (2) the risk of ecosystem collapse using the IUCN Red List of Ecosystems (RLE). These headline indicators are unlikely to facilitate the monitoring of forest integrity for two reasons. First, focusing on forest cover not only misses the impacts of anthropogenic degradation on forests but can also fail to detect the effect of positive management actions in enhancing forest integrity. Second, the risk of ecosystem collapse as measured by the ordinal RLE index (from Least Concern to Critically Endangered) makes it unlikely that changes to the continuum of forest integrity over space and time would be reported by nations. Importantly, forest ecosystems in many biodiverse African and Asian nations remain unassessed with the RLE. As such, many nations will likely resort to monitoring forest cover alone and therefore inadequately report progress against forest integrity goals and targets. We concur that monitoring changes in forest cover and the risk of ecosystem collapse are indeed vital aspects of conservation monitoring. Yet, they are insufficient for the specific purpose of tracking progress against crucial ecosystem integrity components of the GBF’s goals. We discuss the pitfalls of merely monitoring forest cover, a likely outcome with the current headline indicators. Augmenting forest cover monitoring with indicators that capture change in absolute area along the continuum of forest integrity would help monitor progress toward achieving area-based targets related to both integrity and extent of global forests.

Methamphetamine Increases Tubulo-Vesicular Areas While Dissipating Proteins from Vesicles Involved in Cell Clearance.

Cytopathology induced by methamphetamine (METH) is reminiscent of degenerative disorders such as Parkinson's disease, and it is characterized by membrane organelles arranged in tubulo-vesicular structures. These areas, appearing as clusters of vesicles, have never been defined concerning the presence of specific organelles. Therefore, the present study aimed to identify the relative and absolute area of specific membrane-bound organelles following a moderate dose (100 µM) of METH administered to catecholamine-containing PC12 cells. Organelles and antigens were detected by immunofluorescence, and they were further quantified by plain electron microscopy and in situ stoichiometry. This analysis indicated an increase in autophagosomes and damaged mitochondria along with a decrease in lysosomes and healthy mitochondria. Following METH, a severe dissipation of hallmark proteins from their own vesicles was measured. In fact, the amounts of LC3 and p62 were reduced within autophagy vacuoles compared with the whole cytosol. Similarly, LAMP1 and Cathepsin-D within lysosomes were reduced. These findings suggest a loss of compartmentalization and confirm a decrease in the competence of cell clearing organelles during catecholamine degeneration. Such cell entropy is consistent with a loss of energy stores, which routinely govern appropriate subcellular compartmentalization.

From a validated targeted method to a retrospective UHPLC-HRMS non-targeted analysis unveiling COVID-19-related contaminants in clams. Have we bias in marine model organisms for ecotoxicological studies?

This study explores a retrospective non-targeted analysis (NTA), based on Ultra High-Performance Liquid Chromatography coupled to High-Resolution Mass Spectrometry (UHPLC-HRMS), to assess hidden chemicals of emerging concern (CECs) in marine model organisms. Conventional ecotoxicological studies do not include evaluating the natural habitats of the collected organisms, missing the possibility of highlighting unexpected pollutants, and thus compromising the correctness and reliability of the experimental results. In this paper we reprocessed samples previously collected from the Venice Lagoon for ecotoxicological studies and used for targeted analysis of three bisphenols-related compounds (i.e. BPS, BPF and BPAF) on seawater and specimens of the clam Ruditapes philippinarum. Results from the validation were the following: accuracy, expressed as percentage recoveries (R%), in the range 80%<R%<120% for all the considered compounds and matrices, and precision, expressed as relative standard deviation of the absolute areas of IS, was <20% for clams (N = 24) and <15% for seawater (N = 30). LODs ranged from 5 to 50 ng/L for seawater and 5–12 ng/g for clam tissues.After validation, a retrospective NTA was carried out on control samples, showing the presence of some CECs, i.e. Lopinavir, Ritonavir, DEHS, and DEHA, two antiviral drugs used during the COVID-19 pandemic and two plasticizers, respectively, reported here for the first time in the Mediterranean Sea. CEC identifications were confirmed by matching MS/MS spectra with libraries. The present study emphasizes the importance of retrospective investigations to describe the contamination scenario of environmental matrices and the related effect in biota, to correctly address studies on model animals, also including possible “cocktail effects”.

Structural Magnetic Resonance Imaging-Based Surface Morphometry Analysis of Pediatric Down Syndrome.

Down syndrome (DS) is a genetic disorder characterized by intellectual disability whose etiology includes an additional partial or full copy of chromosome 21. Brain surface morphometry analyses can potentially assist in providing a better understanding of structural brain differences, and may help characterize DS-specific neurodevelopment. We performed a retrospective surface morphometry study of 73 magnetic resonance imaging (MRI) examinations of DS patients (aged 1 day to 22 years) and compared them to a large cohort of 993 brain MRI examinations of neurotypical participants, aged 1 day to 32 years. Surface curvature measurements, absolute surface area measurements, and surface areas as a percentage of total brain surface area (%TBSA) were extracted from each brain region in each examination. Results demonstrate broad reductions in surface area and abnormalities of surface curvature measurements across the brain in DS. After adjusting our regional surface area measurements as %TBSA, abnormally increased presentation in DS relative to neurotypical controls was observed in the left precentral, bilateral entorhinal, left parahippocampal, and bilateral perirhinal cortices, as well as Brodmann's area 44 (left), and the right temporal pole. Findings suggest the presence of developmental abnormalities of regional %TBSA in DS that can be characterized from clinical MRI examinations.

Anomalous scalings of fluctuations of the area swept by a Brownian particle trapped in a [formula omitted] potential

We study the fluctuations of the area A=∫0Tx(t)dt under a one-dimensional Brownian motion x(t) in a trapping potential ∼|x|, at long times T→∞. We find that typical fluctuations of A follow a Gaussian distribution with a variance that grows linearly in time (at large T), as do all higher cumulants of the distribution. However, large deviations of A are not described by the “usual” scaling (i.e., the large deviations principle), and are instead described by two different anomalous scaling behaviors: Moderately-large deviations of A, obey the anomalous scaling PA;T∼e−T1/3fA/T2/3 while very large deviations behave as PA;T∼e−TΨA/T2. We find the associated rate functions f and Ψ exactly. Each of the two functions contains a singularity, which we interpret as dynamical phase transitions of the first and third order, respectively. We uncover the origin of these striking behaviors by characterizing the most likely scenario(s) for the system to reach a given atypical value of A. We extend our analysis by studying the absolute area B=∫0T|x(t)|dt and also by generalizing to higher spatial dimension, focusing on the particular case of three dimensions.

Effectiveness and Safety of Upadacitinib for Adolescents with Atopic Dermatitis in a Real-World Setting.

The estimated prevalence of atopic dermatitis (AD) among adolescents (12-17years of age) is about 14.8%. AD compromises sleep quality and may be associated with poor scholastic performance, mood disruptions, low self-esteem, and difficulty in building social relationships. Upadacitinib was recently approved by the European Medicines Agency for the treatment of moderate-to-severe AD in patients aged ≥12years who are candidates for systemic treatment. The aim of this real-world study was to determine the effectiveness in disease control and safety of upadacitinib in adolescents aged 12-17yearswithmoderate-to-severe AD. This is a retrospective study in adolescents with moderate-to-severe AD treated with upadacitinib 15mg between July 2022 and February 2024 at six Italian dermatological referral centres. The primary endpoint was to analyse the evolution of the response in terms of absolute Eczema Area and Severity Index (EASI) value, as well as the percentage of patients achieving 75% and 90% improvement in EASI (EASI75 and EASI90) from baseline to weeks (W) 4, 16, 24, and 52. Secondary endpoints included the assessment of treatment efficacy in terms of Numerical Rating Scale (NRS) for pruritus (P-NRS) and sleep (S-NRS), Children's Dermatology Life Quality Index (c-DLQI), and safety. Thirty-six patients [males: 18 (50%)] were evaluated. A statistically significant improvement of EASI was observed at each timepoint, as stated by a mean percentage reduction from baseline of 72.2% at W4, 82.7% at W16, of 86.4% at W24 (n=34) and of 92.7% at W52 (n=18) (p<0.0001). At W4, 21/36 (58.3%) achieved EASI75 and 12/36 (33.3%) EASI90. At W16, 29/36 (80.5%) achieved EASI75 and 19/36 (52.8%) EASI90. At W24, 32/34 (94.1%) reached EASI75 and 24/34 (70.6%) EASI90. Finally, at W52 all the assessed patients (n=18) maintained EASI75 and 14/18 (77.7%) reached EASI90. Likewise, a statistically significant reduction of c-DLQI, P-NRS and S-NRS was observed at each timepoint. Our real-world experience seems to confirm the efficacy and safety of upadacitinib for the long-term treatment of moderate-to-severe AD in adolescents.

A New Index for Cervical Curvature Evaluation - Relative Cervical Curvature Area

ObjectiveTo put forward a new index of cervical curvature evaluation - relative cervical curvature area,and a new classification of cervical spine was proposed according to the relative cervical curvature area. MethodsA total of 167 subjects with cervical spondylosis were included in the study. Firstly, 119 subjects were selected to measure C2-C7 lordosis angle by Cobb angle method, Harrison posterior tangent method and Jackson physiological stress line method, and then their relative cervical curvature area, C1-C7 Cobb angle, C7 slope and T1 slope were measured.The correlation between relative cervical curvature area and three measurement methods and common sagittal parameters was analyzed.According to the angle classification method, we calculated the diagnostic boundary value of the relative cervical curvature area classification, and selected 48 subjects to evaluate its diagnostic efficacy.Finally, 119 subjects were re-evaluated according to the diagnostic threshold and the number of intersections to verify the feasibility of the new classification. ResultsThe results showed that the relative cervical curvature area index had good intra-observer and inter-observer repeatability. Relative cervical curvature area was correlated with Harrison posterior tangent method ( r = 0.930 ), Cobb angle method ( r = 0.886 ) and Jackson physiological stress line method ( r = 0.920 ), and correlated with C1-C7 Cobb angle, C7 slope and T1 slope.The relative cervical curvature area has a good diagnostic performance for distinguishing patients with lordosis, straightening and kyphosis.According to the new classification of cervical spine, 119 subjects were divided into 57 simple lordosis, 11 simple straightening, 4 simple kyphosis, 26 S-type and 21 RS-type. ConclusionThe relative cervical curvature area uses the area parameter instead of the original angle parameter and distance parameter to incorporate the change of segmental curvature, which makes up for the shortcomings of the Cobb angle method that only evaluates the curvature of two vertebrae, and better reflects the cervical curvature.Studies have shown that relative cervical curvature area has good repeatability and diagnostic value, and found that it has a good correlation with common cervical sagittal parameters.The new classification of cervical spine makes up for the disadvantage that the angle classification method cannot distinguish between S-type and RS-type, and initially proposes to use the number of intersections and the relative absolute value area to reflect the severity of S-type.

Effect of testosterone therapy on breast tissue composition and mammographic breast density in trans masculine individuals

BackgroundThe effect of gender-affirming testosterone therapy (TT) on breast cancer risk is unclear. This study investigated the association between TT and breast tissue composition and breast tissue density in trans masculine individuals (TMIs).MethodsOf the 444 TMIs who underwent chest-contouring surgeries between 2013 and 2019, breast tissue composition was assessed in 425 TMIs by the pathologists (categories of lobular atrophy and stromal composition) and using our automated deep-learning algorithm (% epithelium, % fibrous stroma, and % fat). Forty-two out of 444 TMIs had mammography prior to surgery and their breast tissue density was read by a radiologist. Mammography digital files, available for 25/42 TMIs, were analyzed using the LIBRA software to obtain percent density, absolute dense area, and absolute non-dense area. Linear regression was used to describe the associations between duration of TT use and breast tissue composition or breast tissue density measures, while adjusting for potential confounders. Analyses stratified by body mass index were also conducted.ResultsLonger duration of TT use was associated with increasing degrees of lobular atrophy (p < 0.001) but not fibrous content (p = 0.82). Every 6 months of TT was associated with decreasing amounts of epithelium (exp(β) = 0.97, 95% CI 0.95,0.98, adj p = 0.005) and fibrous stroma (exp(β) = 0.99, 95% CI 0.98,1.00, adj p = 0.05), but not fat (exp(β) = 1.01, 95%CI 0.98,1.05, adj p = 0.39). The effect of TT on breast epithelium was attenuated in overweight/obese TMIs (exp(β) = 0.98, 95% CI 0.95,1.01, adj p = 0.14). When comparing TT users versus non-users, TT users had 28% less epithelium (exp(β) = 0.72, 95% CI 0.58,0.90, adj p = 0.003). There was no association between TT and radiologist’s breast density assessment (p = 0.58) or LIBRA measurements (p > 0.05).ConclusionsTT decreases breast epithelium, but this effect is attenuated in overweight/obese TMIs. TT has the potential to affect the breast cancer risk of TMIs. Further studies are warranted to elucidate the effect of TT on breast density and breast cancer risk.

Minimal clinically important difference (MCID) of effect sizes other than mean difference

It is recommended to report both a P value &lt; 0.05 and an effect size exceeding the minimal clinically important difference (MCID) to assert a meaningful difference or association between two clinical measurements. However, MCIDs for effect sizes other than mean difference has not been established. We aimed to propose study-level MCIDs, based on distribution method and Cohen’s d, for various effect sizes other than the mean difference, such as the hazard ratio (HR), risk ratio (RR), odds ratio (OR), absolute risk difference (ARD), correlation coefficient (r), and area under the receiver operating characteristic curve (AUC). Our primary innovation lies in the conversion between Cohen's d and effect sizes and in introducing flexible MCID for effect sizes not on an interval scale. The proposed MCIDs of the HR are 0.64, 0.76, and 0.83 for d = 0.5, 0.3, and 0.2, respectively, along with their reciprocals. For RR, OR, and ARD, d = |inverse_Φ(risk for experiment) – inverse_Φ(risk for control)|, where Φ represents the cumulative distribution function. For correlation coefficient, d = |f(r for experiment) − f(r for control)|, where f(r) = 2·r/√(1 – r^2). For AUC, d = |√2·inverse_Φ(AUC for experiment) − √2·inverse_Φ(AUC for control)|.The proposed MCID is especially useful for evaluating intergroup differences in meta-analyses, where statistical significance is more easily achieved, for setting detectable differences in superiority trials, and for determining non-inferiority margins in non-inferiority trials.

Effect of nickel and selenium co-doping on molybdenum disulfide structure and its electrochemical activity in polysulfide electrolyte

The development of a low-cost, and highly effective platinum (Pt)-free counter electrode (CE) that is highly stable towards polysulfide electrolyte presents a substantial challenge. Trigonal Molybdenum disulfide (1T-MoS2) has shown good chemical stability toward polysulfide electrolytes. In this study, 1T-MoS2 was prepared by co-doping with nickel (Ni) and selenium (Se) into MoS2 through hydrothermal method and utilizing its reduction activity toward polysulfide electrolyte. According to electrochemical impedance spectroscopy (EIS) analysis, Ni-Se-MoS2 has a low charge transfer resistance and electron recombination lifetime. In addition, cyclic voltmeter (CV) analysis reveals a high absolute area indicating a high level of electrocatalytic activity for polysulfide reduction at the electrolyte/counter electrode (CE) interface. The XRD analysis shows that the phase shifting of 2H MoS2 to 1 T MoS2 and the intensity of the co-doped sample is lower than that of others. SEM analysis reveals a microsphere-flower-like morphology that increases specific surface area.

Topical application of simvastatin acid sodium salt and atorvastatin calcium salt in vitiligo patients. Results of the randomized, double-blind EVRAAS pilot study

Contemporary treatment of vitiligo remains a great challenge to practitioners. The vast majority of currently conducted clinical trials of modern therapeutic methods are focused on systemic medications, while there is only a very limited number of reports on new topical treatment in vitiligo. With their pleiotropic activities statins turned out to be efficient in the treatment of various autoimmune/autoinflammatory disorders. The randomized, double-blind placebo-controlled study of topical administration of the active forms of simvastatin and atorvastatin has been designed to evaluate their efficacy in patients with vitiligo. The study was registered in clinicaltrials.gov (registration number NCT03247400, date of registration: 11th August 2017). A total of 24 patients with the active form of non-segmental vitiligo were enrolled in the study. The change of absolute area of skin lesions, body surface area and vitiligo area scoring index were evaluated throughout the 12 week application of ointments containing simvastatin and atorvastatin. Measurements were performed with planimetry and processed using digital software. Use of active forms of simvastatin and atorvastatin did not result in a significant repigmentation of the skin lesions throughout the study period. Within the limbs treated with topical simvastatin, inhibition of disease progression was significantly more frequent than in the case of placebo (p = 0.004), while the difference was not statistically significant for atorvastatin (p = 0.082). Further studies of topical simvastatin in vitiligo patients should be considered.