Evaluation of the Potential of AI to Foster Gender Diversity in Leadership Positions in Germany

Women remain underrepresented in leadership positions in Germany. This article explores whether AI could support gender diversity in leadership. After analyzing current diversity data, we identified hurdles for women in leadership from literature. We evaluated AI’s potential to promote gender diversity through examples of AI tools from professional and private life. Four potential areas for AI assistance were identified: i) recruitment, ii) personalized time-management, iii) career development, and iv) networking and mentoring. These AI tools could particularly benefit women by addressing identified obstacles. The literature on this specific topic is limited, making this article a valuable foundation for further research

Design and rationale for a global novel non-invasive screening observational study using genetics and non-invasive methodologies to identify at-risk MASLD participants: The ALIGN study.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common chronic liver disease that is heterogenous in nature with various drivers and modifiers such as metabolic dysfunction and genetic factors. MASLD and the progressive subtype, metabolic dysfunction-associated steatohepatitis (MASH) represent the most rapidly increasing cause of liver-related mortality. There are limited treatment options for patients living with MASLD and MASH, various treatments with an array of different targets are under investigation and one therapeutic has been approved since the initiation of this study. Clinical trials investigating treatments for MASLD and MASH are associated with a high screen failure rate, driven largely by the regulatory required histological inclusion criteria for clinical trial eligibility. Other available clinically utilized biomarkers, typically referred to as non-invasive tests (NITs), can assess both the presence of steatosis and the severity of liver fibrosis in patients with MASLD and MASH in the clinic but are not yet approved over histological changes as endpoints for pivotal trials. However, the use of NITs have been demonstrated to increase the likelihood of meeting clinical trial entry criteria. All-Liver Interventional Global Network (ALIGN) is the first described multi-centre global observational screening study aimed at identifying individuals with a high likelihood of MASLD/MASH interested in participating in therapeutic clinical trials using non-invasive methodologies and genetic testing. This study represents a valuable prototype for industry and academic groups looking to evaluate large populations for MASH eligibility and interest in clinical trial participation

Vaccination against GIP for the treatment of obesity.

BACKGROUND: According to the WHO, more than 1 billion people worldwide are overweight and at risk of developing chronic illnesses, including cardiovascular disease, type 2 diabetes, hypertension and stroke. Current therapies show limited efficacy and are often associated with unpleasant side-effect profiles, hence there is a medical need for new therapeutic interventions in the field of obesity. Gastric inhibitory peptide (GIP, also known as glucose-dependent insulinotropic polypeptide) has recently been postulated to link over-nutrition with obesity. In fact GIP receptor-deficient mice (GIPR(-/-)) were shown to be completely protected from diet-induced obesity. Thus, disrupting GIP signaling represents a promising novel therapeutic strategy for the treatment of obesity. METHODOLOGY/PRINCIPAL FINDINGS: In order to block GIP signaling we chose an active vaccination approach using GIP peptides covalently attached to virus-like particles (VLP-GIP). Vaccination of mice with VLP-GIP induced high titers of specific antibodies and efficiently reduced body weight gain in animals fed a high fat diet. The reduction in body weight gain could be attributed to reduced accumulation of fat. Moreover, increased weight loss was observed in obese mice vaccinated with VLP-GIP. Importantly, despite the incretin action of GIP, VLP-GIP-treated mice did not show signs of glucose intolerance. CONCLUSIONS/SIGNIFICANCE: This study shows that vaccination against GIP was safe and effective. Thus active vaccination may represent a novel, long-lasting treatment for obesity. However further preclinical safety/toxicology studies will be required before the therapeutic concept can be addressed in humans

Norms of Presentational Force

This is the author's accepted manuscript, made available with permission of the American Forensic Association.Can style or presentational devices reasonably compel us to believe, agree, act? I submit that they can, and that the normative pragmatic project explains how. After describing a normative pragmatic approach to presentational force, I analyze and evaluate presentational force in Susan B. Anthony's "Is it a Crime for a U. S. Citizen to Vote" as it apparently proceeds from logic, emotion, and style. I conclude with reflections on the compatibility of the normative pragmatic approach with the recently-developed pragma-dialectical treatment of presentational devices

Opportunistic infections in immunosuppressed patients with juvenile idiopathic arthritis: Analysis by the Pharmachild Safety Adjudication Committee

Background: To derive a list of opportunistic infections (OI) through the analysis of the juvenile idiopathic arthritis (JIA) patients in the Pharmachild registry by an independent Safety Adjudication Committee (SAC). Methods: The SAC (3 pediatric rheumatologists and 2 pediatric infectious disease specialists) elaborated and approved by consensus a provisional list of OI for use in JIA. Through a 5 step-procedure, all the severe and serious infections, classified as per MedDRA dictionary and retrieved in the Pharmachild registry, were evaluated by the SAC by answering six questions and adjudicated with the agreement of 3/5 specialists. A final evidence-based list of OI resulted by matching the adjudicated infections with the provisional list of OI. Results: A total of 772 infectious events in 572 eligible patients, of which 335 serious/severe/very severe non-OI and 437 OI (any intensity/severity), according to the provisional list, were retrieved. Six hundred eighty-two of 772 (88.3%) were adjudicated as infections, of them 603/682 (88.4%) as common and 119/682 (17.4%) as OI by the SAC. Matching these 119 opportunistic events with the provisional list, 106 were confirmed by the SAC as OI, and among them infections by herpes viruses were the most frequent (68%), followed by tuberculosis (27.4%). The remaining events were divided in the groups of non-OI and possible/patient and/or pathogen-related OI. Conclusions: We found a significant number of OI in JIA patients on immunosuppressive therapy. The proposed list of OI, created by consensus and validated in the Pharmachild cohort, could facilitate comparison among future pharmacovigilance studies. Trial registration: Clinicaltrials.gov NCT 01399281; ENCePP seal: awarded on 25 November 2011

Dendritic Cell Subset Distributions in the Aorta in Healthy and Atherosclerotic Mice

Dendritic cells (DCs) can be sub-divided into various subsets that play specialized roles in priming of adaptive immune responses. Atherosclerosis is regarded as a chronic inflammatory disease of the vessel wall and DCs can be found in non-inflamed and diseased arteries. We here performed a systematic analyses of DCs subsets during atherogenesis. Our data indicate that distinct DC subsets can be localized in the vessel wall. In C57BL/6 and low density lipoprotein receptor-deficient (Ldlr−/−) mice, CD11c+ MHCII+ DCs could be discriminated into CD103− CD11b+F4/80+, CD11b+F4/80− and CD11b−F4/80− DCs and CD103+ CD11b−F4/80− DCs. Except for CD103− CD11b− F4/80− DCs, these subsets expanded in high fat diet-fed Ldlr−/− mice. Signal-regulatory protein (Sirp)-α was detected on aortic macrophages, CD11b+ DCs, and partially on CD103− CD11b− F4/80− but not on CD103+ DCs. Notably, in FMS-like tyrosine kinase 3-ligand-deficient (Flt3l−/−) mice, a specific loss of CD103+ DCs but also CD103− CD11b+ F4/80− DCs was evidenced. Aortic CD103+ and CD11b+ F4/80− CD103− DCs may thus belong to conventional rather than monocyte-derived DCs, given their dependence on Flt3L-signalling. CD64, postulated to distinguish macrophages from DCs, could not be detected on DC subsets under physiological conditions, but appeared in a fraction of CD103− CD11b+ F4/80− and CD11b+ F4/80+ cells in atherosclerotic Ldlr−/− mice. The emergence of CD64 expression in atherosclerosis may indicate that CD11b+ F4/80− DCs similar to CD11b+ F4/80+ DCs are at least in part derived from immigrated monocytes during atherosclerotic lesion formation. Our data advance our knowledge about the presence of distinct DC subsets and their accumulation characteristics in atherosclerosis, and may help to assist in future studies aiming at specific DC-based therapeutic strategies for the treatment of chronic vascular inflammation

The expression of Cortactin and EGFR in human head and neck squamous cell carcinoma

In dieser Arbeit wurden die Expressionen von Cortactin und EGFR in 222 Gewebeproben von humanen Plattenepithelkarzinomen des Kopf-Hals-Bereichs (HNSCC) immunhistochemisch bewertet. Die statistische Analyse zeigte Zusammenhänge zwischen den Expressionen der Proteine selbst sowie zwischen den Proteinexpressionen und klinischen Parametern wie Auftreten von Rezidiven und Überleben der Patienten. Die Expressionen von Cortactin und EGFR könnten weitere Hilfe für die Therapiestrategie bei HNSCC bieten.This study examines the expressions of cortactin and EGFR via immunohistochemistry in 222 tissues of human head and neck squamous cell carcinomas (HNSCC). Statistical analysis showed correlations between the expressions of the proteins themselves as well as between the protein expressions and clinical parameters such as recurrence and survival. Expressions of cortactin and EGFR could open new options for therapy strategy in HNSCC

Pioneer personal history, Alma Lutz

Typescript of a biographical sketch of Alma Lutz, from an interview. He was born in Pennsylvania in 1841, and his family moved to Nauvoo and were at Winter Quarters before crossing the plains to Utah. He lived at Smithfield, Randolph, Moab, and Provo. Typed by Arnel Holyoak of Moab in 193

Vaccination against GIP for the Treatment of Obesity

BACKGROUND: According to the WHO, more than 1 billion people worldwide are overweight and at risk of developing chronic illnesses, including cardiovascular disease, type 2 diabetes, hypertension and stroke. Current therapies show limited efficacy and are often associated with unpleasant side-effect profiles, hence there is a medical need for new therapeutic interventions in the field of obesity. Gastric inhibitory peptide (GIP, also known as glucose-dependent insulinotropic polypeptide) has recently been postulated to link over-nutrition with obesity. In fact GIP receptor-deficient mice (GIPR(−/−)) were shown to be completely protected from diet-induced obesity. Thus, disrupting GIP signaling represents a promising novel therapeutic strategy for the treatment of obesity. METHODOLOGY/PRINCIPAL FINDINGS: In order to block GIP signaling we chose an active vaccination approach using GIP peptides covalently attached to virus-like particles (VLP-GIP). Vaccination of mice with VLP-GIP induced high titers of specific antibodies and efficiently reduced body weight gain in animals fed a high fat diet. The reduction in body weight gain could be attributed to reduced accumulation of fat. Moreover, increased weight loss was observed in obese mice vaccinated with VLP-GIP. Importantly, despite the incretin action of GIP, VLP-GIP-treated mice did not show signs of glucose intolerance. CONCLUSIONS/SIGNIFICANCE: This study shows that vaccination against GIP was safe and effective. Thus active vaccination may represent a novel, long-lasting treatment for obesity. However further preclinical safety/toxicology studies will be required before the therapeutic concept can be addressed in humans