bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simone Weil et les dimensions mystiques de la nourriture
Authors: Salihbegovic Nejra 
Published: January 2024

This article aims to examine the mystical meanings of food in the texts Gravity and Grace, Waiting for God, and First and Last Notebooks by the French philosopher Simone Weil (1909-1943). The main questions posed over the course of this study are as follows: How does Weil interpret food in her mystical texts? What relationship do her ideas have with her context of the Second World War, with Judaism, with her body? Are biomedical understandings of behavior, such as anorexia nervosa, applicable to Weil? The methodology will involve an in-depth reading of the three texts mentioned above, sketching the key theories of decreation and affliction. The main thesis of the paper is that food has an irremediably ambiguous status in Weil, marking both the degrading subjection of the human being to the earthly laws of necessity and gravity, and paradoxically, a path to salvation, where, through the spiritual transformation of decreation, the human being eats and is eaten by God. The author argues that this quasi-Christian mysticism must first be understood in Weil’s context of the Second World War, and that it also involves a problematic relationship with Judaism. Moreover, this study contends that interpretations utilizing primarily medical frameworks to understand Weil's food deprivation, such as anorexia nervosa, are insufficient. Such pathologization, as will be demonstrated, neglects the complex and often ambiguous mystical, ethical, and ontological meanings that Weil locates in hunger.
Cost-per-Responder Analysis of Tralokinumab versus Dupilumab in Patients with Moderate-to-Severe Atopic Dermatitis in the US and Canada
Authors: Wu Jashin , Balu Sanjeev , Birk Larsen Nikolaj , Pulleyblank Ryan , Strømkjær Liv , Quah Aron , Wiseman Marni 
Published: January 2024

Introduction and objective: Biologic treatments such as tralokinumab and dupilumab are therapeutic options for adult patients with moderate-to-severe atopic dermatitis (AD) who do not achieve adequate control with topical treatments or phototherapy. To date, no trials have been conducted to directly evaluate the relative efficacy of these biologic treatments. Applying indirect comparison of efficacy, we examined the cost-per-responder of tralokinumab compared to dupilumab in combination with topical corticosteroids (TCS) for the treatment of moderate-to-serve AD in the United States (US) and Canada.
Method: A cost-per-responder analysis was undertaken considering the Eczema Area and Severity Index 75 (EASI-75) and Investigator’s Global Assessment (IGA-0/1) response criteria over a 32-week period. For each treatment, the cost-per-responder was computed by multiplying the treatment cost by the number needed to treat (NNT). Efficacy data were derived from an unanchored matching-adjusted indirect comparison (MAIC) utilizing patient-level data from ECZTRA-3 (tralokinumab) and aggregate data from LIBERTY AD CHRONOS (dupilumab). Treatment cost was defined as the drug cost of the biologic treatment with a duration corresponding to 32 weeks. TCS cost was not considered. Treatments were assumed to be administered every 2 weeks (Q2W). The costs were estimated based on Wholesale Acquisition Costs (WAC) from the US and ex-factory prices via the McKesson price list for Canada. All prices were converted to US dollars ($). Sensitivity analyses (SA) were conducted with every 4 week (Q4W) dosing beginning at week 16 for 10% and 20% of patients treated with tralokinumab.
Results: For the US, the average cost-per-responder was $62,714 (Q4W SA: 10%: $61,239; 20%: $59,763) for tralokinumab versus $63,993 for dupilumab considering the EASI-75 response criteria, while the average cost-per-responder was $82,419 (Q4W SA: 10%: $80,480; 20%: $78,450) for tralokinumab versus $118,835 for dupilumab considering the IGA 0/1 response criteria. For Canada, the average cost-per-responder was $22,846 (Q4W SA: 10%: $22,308; 20%: $21,771) for tralokinumab versus $26,475 for dupilumab considering the EASI-75 response criteria, while the average cost-per-responder was $30,024 (Q4W SA: 10%: $29,317; 20%: $28,611) for tralokinumab versus $49,165 for dupilumab considering the IGA 0/1 response criteria.
Conclusion: Assessing EASI-75 and IGA-0/1 response criteria at 32 weeks, this analysis indicates that tralokinumab in combination with TCS is associated with lower costs-per-responder compared with dupilumab in combination with TCS in the treatment of moderate-to-severe AD in the US and Canada.
Tralokinumab Real-World Patient-Reported Outcomes in Moderate-to-Severe Atopic Dermatitis Adult Patients in the United States: 6-Month Interim Analysis
Authors: Lio Peter , Kim Yestle , Balu Sanjeev , Costantino Halley , Bates Dawn , Rene Cassandra , Lopez Amanda , Soung Jennifer 
Published: January 2024

Introduction: Tralokinumab, an IL-13 targeted biologic approved in the United States (US) for adult patients with moderate-to-severe atopic dermatitis (AD), improved patient-reported outcomes (PROs) in clinical trials and after 4 weeks of use in the real-world setting. This 6-month interim analysis evaluated the real-world impact of tralokinumab on PROs in adult patients.
Methods: This is an interim analysis of an ongoing 52-week patient survey study enrolling US AD patients from the AdbryTM AdvocateTM Program. Patients completed the baseline survey close to tralokinumab initiation. Data on demographics and PROs including weekly itch numeric rating scale (NRS), eczema-related weekly sleep NRS, Dermatology Life Quality Index (DLQI), and Treatment Satisfaction Questionnaire for Medication (TSQM-9) were collected. Percent and absolute changes from baseline to 6 months of treatment were calculated. Outcomes are stratified by previous dupilumab use. The percentage of patients experiencing minimal clinically important difference (MCID) was also calculated for itch NRS (3-point reduction) and DLQI (4-point reduction).
Results: As of May 2023, 102 patients completed baseline, 1-month, and 6-month surveys. Of these, 59.8% were female, mean age was 44.2 years (SD=15.7), 82.4% were white, and 85.3% had private insurance. 84.3% were previously treated with topical corticosteroids (TCS) and 52.9% were dupilumab-experienced patients. Over 6 months, there was an improvement in the mean sleep interference NRS (40%), average weekly itch NRS (39%), worst weekly itch NRS (33%), PO-SCORAD (37%), and DLQI (52%). There were improvements in mean TSQM-9 global satisfaction (11.06 points), TSQM-9 convenience (3.92 points), and TSQM-9 effectiveness (14.60 points) scores. Median MCIDs were met by 57.1% on the sleep interference NRS, 51.7% of patients on the average weekly itch NRS, 50.0% on the worst weekly itch NRS, and 68.7% on the DLQI. Relative to the dupilumab-experienced cohort, the dupilumab-naïve patients showed markedly improved outcomes [median MCIDs of 65.6% v 48.4% on sleep NRS; 59.5% v 44.4% on average weekly itch NRS; 61.4% v 39.6% on worst weekly itch NRS; 61.4% v 35.3% on PO-SCORAD; and 75.6% v 61.9% on DLQI].
Conclusion: This 6-month interim analysis shows that tralokinumab improved quality of life outcomes related to itch, sleep, and treatment satisfaction when used either in dupilumab-naïve or in dupilumab-experienced patients. These patients will continue to be followed for up to 52 weeks of treatment with tralokinumab.
Tralokinumab Improves Signs and Symptoms of Moderate-to-Severe Atopic Dermatitis in Patients Aged 12 years and Older With and Without Atopic Comorbidities
Authors: Paller Amy , Soong Weily , Boguniewicz Mark , Geng Bob , Thyssen Jacob , Rosso Aldana , Steffensen Louise , Schneider Shannon , Wollenberg Andreas 
Published: January 2024

Background: Atopic dermatitis (AD) is an inflammatory skin disease associated with atopic comorbidities, including asthma, food allergy, hay fever, and allergic conjunctivitis. Tralokinumab, a high-affinity monoclonal antibody that specifically targets IL-13, is indicated for the treatment of moderate-to-severe AD. We assessed the impact of atopic comorbidities on the efficacy and safety of tralokinumab vs. placebo for moderate-to-severe AD in patients age ≥12 years.
Methods: This post-hoc analysis presents data from the adult trials ECZTRA 1 and 2 (NCT03131648 and NCT03160885 pooled; 300 mg tralokinumab every 2 weeks [Q2W] vs. placebo) and ECZTRA 3 (NCT03363854; 300 mg tralokinumab Q2W vs. placebo, both plus TCS as needed), and the ECZTRA 6 adolescent trial (NCT03526861; pooled 150 mg and 300 mg tralokinumab Q2W vs. placebo). Tralokinumab-treated patients received a loading dose. Proportion of patients achieving IGA 0/1 and EASI-75 at Week 16 according to patient-reported current or past atopic comorbidity are presented as observed regardless of rescue medication use; missing data were imputed as non-responders.
Results: In total 2,223 patients were included across four trials. Among patients in ECZTRA 1 and 2, 50.5% reported history of asthma, 38.5% food allergy, 53.8% hay fever, and 33.5% allergic conjunctivitis, while 19.8% reported no atopic comorbidities and 79.3% reported ≥1 atopic comorbidity. Proportions of patients in ECZTRA 3 and 6 reporting history of atopic comorbidities were largely similar, although more adolescent patients reported food allergy. In all subgroups at Week 16, higher proportions of patients receiving tralokinumab vs. placebo achieved EASI-75. In ECZTRA 1 and 2, response rates among patients in each subgroup were asthma: 35.3% vs. 12.8%, food allergy: 33.2% vs. 14.7%, hay fever: 36.8% vs. 16.5%, allergic conjunctivitis: 34.8% vs. 12.7%, none: 34.6% vs. 20.5%; and ≥1 atopic comorbidity: 35.5% vs. 15.2% (P<0.05 for all). A similar pattern of response was observed in ECZTRA 3 and 6, and for IGA 0/1 across trials. EASI-75 response rates for tralokinumab-treated patients were consistent across patients with different numbers of atopic comorbidities. Safety across subgroups was consistent with the safety profile of tralokinumab observed overall in adults and adolescents.
Conclusions: 16 weeks of tralokinumab treatment improved AD signs and symptoms in adult and adolescent patients with and without atopic comorbidities, regardless of type or number of atopic comorbidities. The safety profile of tralokinumab was consistent between patients with and without atopic comorbidities.
Incorporating the 40-Gene Expression Profile (40-GEP) Test within Each Clinicopathologic Staging System Improves Metastatic Risk-Stratification in Patients Diagnosed with Cutaneous Squamous Cell Carcinoma (cSCC) and One or More High Risk Factors
Authors: Wysong Ashley , Somani Ally‐Khan , Ibrahim Sherrif , Cañueto Javier , Fitzgerald Alison , Siegel Jennifer , Prasai Anesh , Goldberg Matthew , Farberg Aaron , Kasprzak Julia , Brodland David , Koyfman Shlomo , Arron Sarah 
Published: January 2024

Purpose: Three clinicopathologic-based risk assessment systems (Brigham and Women’s Hospital (BWH) staging, American Joint Committee on Cancer 8th Edition (AJCC8) staging or National Comprehensive Cancer Network (NCCN)) are used to guide treatment pathway decisions, including nodal assessment and adjuvant radiation therapy. Each of these systems suffers from accuracy limitations. The 40-GEP test was developed to use tumor biology to predict regional/distant metastasis and has previously been validated as an independent risk stratification test for cSCC patients who are diagnosed with one or more clinicopathologic risk factors. The purpose of this study was to evaluate the performance of the 40-GEP test in the prognostication of metastasis when results are used in the context of each of the clinicopathologic risk assessment system.
Study: Under an IRB-approved protocol, centralized pathology review, and sample analysis were performed in a CAP-accredited, CLIA-certified laboratory using formalin-fixed paraffin-embedded archival primary SCC tumor specimens with one or more risk factors (n=897). Verified clinicopathologic information and outcomes data were collected from 58 contributing centers. Three-year risk stratification for regional and distant metastasis was assessed using Kaplan-Meier analysis for metastasis-free survival (MFS) for Class 1 (low risk), Class 2A (moderate risk), and Class 2B (high risk) groups. Nested Cox regression models and accuracy metrics were used to compare risk prediction of clinicopathologic risk assessment vs. clinicopathologic risk assessment in combination with 40-GEP.
Results: The overall cohort had a metastasis rate of 13.2%, substantiating the high-risk status of this population. For the overall cohort, the 40-GEP test showed clinically and statistically significant differences in MFS rates between Class 1 (94.1%), Class 2A (81.1%), and Class 2B (56.8%) (p<0.001, log-rank). Combining the results of the 40-GEP test with staging systems or NCCN risk categories led to increases in both NPV and PPV, indicating that a 40-GEP result improves the prediction of metastatic risk over the use of staging alone Table 1. Inclusion of 40-GEP with different clinicopathologic risk assessment methods (BWH and AJCC8, or NCCN risk subgroups) yielded significant improvements in prediction of metastatic events compared to each risk assessment method that did not include 40-GEP (ANOVA for deviance, p<0.0001 for each comparison).
Conclusions: Incorporating the 40-gene expression profile (40-GEP) test within each clinicopathologic risk assessment system improves risk-stratification, enabling more accurate treatment pathway decisions.
Safety and Tolerability of Fixed-Dose Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel in Black Participants With Acne
Authors: Callender Valerie , Cook-Bolden Fran , Kircik Leon , Weiss Jonathan , Alexis Andrew , Gold Michael , Tanghetti Emil , Baldwin Hilary , Stein Gold Linda , Sugarman Jeffrey 
Published: January 2024

Background: As acne can cause inflammation-associated sequelae (eg, post-inflammatory hyperpigmentation) in individuals with melanin-rich skin, effective and rapid management must be balanced with minimization of skin irritation. Clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (IDP-126) polymeric mesh gel is the first fixed-dose, triple-combination topical acne product in development. In clinical studies, over half of participants achieved treatment success with IDP-126 gel after 12 weeks. The objective of this pooled, post hoc analysis was to evaluate safety and tolerability of IDP-126 gel in Black participants.
Methods: In two identical phase 3, double-blind, randomized, 12-week studies (NCT04214639; NCT04214652), participants aged ≥9 years with moderate-to-severe acne were randomized (2:1) to receive once-daily IDP-126 or vehicle gel. Assessments included treatment-emergent adverse events (TEAEs) and cutaneous safety/tolerability (hyperpigmentation, hypopigmentation, erythema, scaling, itching, burning, and stinging; graded from 0 [none] to 3 [severe]). Post hoc analyses were based on participants’ self-identification of race as ‘Black or African American’ (hereafter referred to as Black).
Results: Of 363 randomized participants, 54 (14.9%) self-identified as Black. No serious TEAEs were reported and no TEAEs led to discontinuation. Treatment-related TEAEs were reported in 7 (17.5%) IDP-126-treated Black participants; the most common were application site pain (n=5 [12.5%]) and application site pruritus (n=2 [5.0%]). No vehicle-treated participants reported treatment-related TEAEs. TEAEs in Black participants were generally similar to the overall population.
Mean severity scores for all cutaneous safety/tolerability assessments following IDP-126 treatment were <0.55 at all study visits (1=mild). Rates of hyperpigmentation remained relatively unchanged throughout the study while erythema decreased by over 10% from baseline to week 12 with IDP-126 treatment. Rates of all other cutaneous safety/tolerability assessments were low (<9%) at both baseline and week 12.
Conclusions: Clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (IDP-126) gel was safe and well tolerated in Black participants with moderate-to-severe acne over 12 weeks, with no discontinuations or serious TEAEs. Additionally, IDP-126 treatment led to improved erythema in Black participants and no substantial increases in hyperpigmentation. These post hoc analyses add valuable information to the limited literature describing treatment effects and tolerability of novel acne therapeutics in Black individuals.
Support: Ortho Dermatologics.
Topical Clindamycin For Acne Vulgaris: Pharmacovigilance Safety Review and Retrospective Analysis of Gastrointestinal Events
Authors: Pelet del Toro Natalia , Strunk Andrew , Wu Jashin , Stein Gold Linda , Del Rosso James , Brodell Robert , Han George 
Published: January 2024

Background: Clindamycin, a lincosamide antibiotic, was the 125th most prescribed medicine in the US in 2020. Topical formulations that combine clindamycin with benzoyl peroxide or a retinoid are commonly used for acne vulgaris (AV) treatment. While oral and topical clindamycin carry warnings/contraindications regarding the development of gastrointestinal (GI) adverse events (AEs), the real-world incidence of these AEs with topical clindamycin is unknown. The objective is to provide an overview of safety data for topical clindamycin when used for AV treatment.
Methods: Safety data from published literature on PubMed® (case reports, clinical trials data, retrospective data), previously unpublished worldwide pharmacovigilance data (from January 1, 1900-December 31, 2022), and two unpublished retrospective cohort studies of US electronic medical records (EMR; January 1, 2011 to January 31, 2019) were reviewed, with a focus on inflammatory bowel disease (IBD) and GI AEs following topical clindamycin monotherapy or combination treatment
Results: There have been only 4 published case reports of topical clindamycin-associated GI AEs, which were all published between the years 1981-1997. In 8 published pivotal phase 3 clinical trials of topical clindamycin monotherapy or combination treatment for AV, GI-related AEs were reported in 1.4% of clindamycin-treated participants (38/2,672; safety populations). According to the pharmacovigilance data, the rate of GI-related adverse drug reactions with topical clindamycin-containing products was 0.000045% (64/141,084,533). In 1 published retrospective report, there were 0 reports of colitis from the 1,124 patients estimated to have received topical clindamycin prescriptions in the years 1977-1980. In the first retrospective EMR study, results indicate that physicians prescribe topical clindamycin for AV treatment equally to patients with a history of IBD (19.0%; 98/515) or without (20.7%; 14,495/70,151). The second retrospective EMR study showed that among patients with AV and an initial prescription for topical clindamycin (monotherapy or combination; n=18,012), there were 3 (0.02%) incident cases of pseudomembranous colitis within 30 days; none of these cases had a history of IBD.
Conclusions: A review of published case reports, clinical trials safety data, worldwide pharmacovigilance data, and retrospective US prescription data demonstrate that GI events—including colitis or pseudomembranous colitis—in patients exposed to topical clindamycin is extremely low, regardless of IBD history.
Support: Ortho Dermatologics
Аналіз методу багатофакторної аутентифікації користувачів інформаційних систем на основі райдужної оболонки ока
Authors: Стасєв Ю. В. , Гончаренко К. Г. , Мороз В. І. 
Published: January 2024

Необхідність розвитку процесів управління Збройними Силами України обумовлює розробку нових засобів захисту інформаційних систем. Однією з актуальних задач розвитку інформаційних систем на сучасному етапі є забезпечення надійного захисту інформації. Захист інформації тісно пов’язаний з процесом аутентифікації користувачів, адже допуск зловмисника до конфіденційної інформації призведе до втрати або підміни даних, що, в свою чергу, може призвести до негативних політичних і економічних наслідків, стати причиною втрати людських і матеріальних ресурсів. Важливою та ще не вирішеною проблемою захисту інформації є ефективна аутентифікація користувача, який отримує доступ до конфіденційної інформації. Існують різні підходи для надання відповідних повноважень абонентам. Одним з перспективних методів аутентифікації користувачів є сканування райдужної оболонки ока. На сьогоднішній день є невирішена задача оцінки ймовірнісно-часових характеристик аутентифікації користувачів в інформаційних системах на основі сканування райдужної оболонки ока. В статті розглядається метод багатофакторної аутентифікації користувачів інформаційних систем на основі райдужної оболонки ока. Проведено аналіз головних загроз, які можуть виникати під час процесу аутентифікації, виявлені основні переваги та недоліки методу аутентифікації користувачів за райдужною оболонкою ока та отримано вирази для обчислення ймовірності помилки та залежність відношення ймовірності помилкової аутентифікації до кількості ступенів захисту, потрібних для досягнення необхідного рівня безпеки.
Functional Outcome of Locking Compression Plate in Distal Femur Fractures
Authors: Gupta Gaurav , Sah Rabins Kumar , Thakur Prashant , Ruhullaha M. , Thapa Subash 
Published: January 2024

Introduction: Distal femur fracture is common in young people with high velocity injury. Management of distal femur fractures is a therapeutic challenge in orthopedics practice due to its extensive soft tissue injuries, bone loss, comminution, articular extension, instability.Open reduction with internal fixation replaces previous trend of closed conservative management and external fixation. Distal femoral locking compression plate (DF-LCP) requires both locking and compression screw fixation of the femur shaft. DF-LCP has been rapidly adopted as an alternative to intramedullary nails, blade plates and non-locking condylar screw.Materials and Methods: Prospective interventional study was done in department of orthopedics at National Medical College and Teaching Hospital, Birgunj for one year among 45 patients of age more than 18 years with post traumatic closed or open GA Type I, II distal femur fractures, AO Muller type A and C fractures. Ethical approval was obtained from institutional review committee and proper informed consent was taken. Type of implant used was DF-LCP.NEER’S scoring system was used for functional outcome.Results: Out of 45 patients, 42 patients with distal femur fracture were treated by DF-LCP.Three patients lostduring follow up hence removed from study. Out of 42 patients, mean age of the patients was 36.62 years. Most of them 31, (73.8%) were male. Predominant fracture was on right side 29 (69%).The study finding showed that 30 (71.4%) sustained injury due to road traffic accidents. Most of the patients 18 (42.9%) had type A2 fracture according to AO Muller distal femur fracture classification. Complications like surgical site infection observed in 3 cases. 100% union rate achieved with an average union time of 17.26 weeks. On evaluation according to Neer’s criteria mean score was 82.1 (Range: 48-96). Out of 42 patients 24 (57%) had excellent, 14 (33%) had good, 3 (7.2%) had fair and 1 (2.4%) had poor result.Conclusion: The study concluded DF-LCP is effective treatment for distal femur fracture. It provides stable construct for fracture union with excellent functional outcome.