Windsor Dermatology

Creatine, a naturally occurring guanidine carboxylic acid, serves as a critical energy metabolite in tissues with high energy demands. Certain cancers upregulate creatine metabolism to supplement their energy needs. Ompenaclid, a salt form of the well-studied creatine transporter inhibitor 3-guanidinopropionic acid (β-GPA), is in clinical development for the treatment of patients with colorectal tumors. Existing SLC6A8 inhibitors are low-potency molecules and frequently interact with related transporters. Herein, we report the discovery of SLC6A8 inhibitors with increased selectivity as well as in vitro and in vivo potency. A bioisostere approach was used by replacing the carboxylic acid of β-GPA with surrogate functional groups to achieve these improvements. Docking of these inhibitors into the recently published SLC6A8 cryo-EM structure reveals key binding contacts and supports the observed structure-activity relationships.

Patients with moderate-to-severe atopic dermatitis (AD) who discontinue dupilumab need additional therapeutic options. Lebrikizumab's distinct mechanism of action may provide that alternative treatment. We evaluated efficacy and safety of lebrikizumab in adults and adolescents with moderate-to-severe AD previously treated with dupilumab. In the open-label ADapt trial, patients who discontinued dupilumab due to inadequate response, adverse events (AEs)/intolerance, or other reasons received lebrikizumab 250-mg every 2weeks (Q2W) following 500-mg loading dose at baseline/week2, through week16, with optional topical therapy. From weeks16-24, responders (≥ 75% improvement in Eczema Area and Severity Index [EASI75] or Investigator's Global Assessment score 0/1 with ≥ 2-point improvement from baseline) received lebrikizumab every 4weeks; inadequate responders continued lebrikizumab Q2W. The primary endpoint was EASI75 at week16 in the intent-to-treat population; EASI75 was also analyzed by reason for dupilumab discontinuation. Secondary and exploratory efficacy endpoints were assessed throughout. Among the 86 patients enrolled, primary reasons for stopping dupilumab were inadequate response (n = 48, 55.8%), AEs/intolerance (n = 14, 16.3%), and other reasons (n = 24, 27.9%). Fifty-nine patients (68.6%) completed week16; 52 patients (60.5%) completed week24. At weeks16 and 24, respectively, response rates were 57.4% (35/61) and 60.0% (33/55) for EASI75; 53.2% (25/47) and 61.5% (24/39) for Pruritus Numeric Rating Scale ≥ 4-point improvement; and 83.0% (44/53) and 83.0% (39/47) for Dermatology Life Quality Index ≥ 4-point improvement. Most treatment-emergent AEs were mild/moderate. Serious AEs and discontinuations due to AEs were reported by 2 (2.3%) and 5 (5.8%) patients, respectively. Of the 10 patients who discontinued dupilumab due to eye-related events, facial dermatitis, or inflammatory arthritis, none reported similar events with lebrikizumab. Results suggest that lebrikizumab provides meaningful improvements in skin clearance, itch, and quality of life in dupilumab-experienced patients with moderate-to-severe AD, with a safety profile consistent with other lebrikizumab phase3 trials. ClinicalTrials.gov identifier, NCT05369403.

The True VieI3 continuous glucose monitoring system (i3 CGM, Sinocare Meditech Inc., also approved in Europe as GlucoMen® iCan or iCan CGM system) is a new real-time continuous glucose monitoring system (CGM) intended for the management of diabetes mellitus. This pivotal study evaluated the performance of the factory-calibrated CGM system. In this center-specific dataset, 35 adults with type1 diabetes (T1D) and type2 diabetes (T2D) wore sensors on the abdomen and arm for 15days. Four in-clinic visits were scheduled, during which frequent comparator sampling of venous blood was performed every 5-15min for up to 10h, and a glucose manipulation was performed. CGM performance compared to Yellow Springs Instrument 2300 Stat Plus Glucose and Lactate Analyzer (Yellow Springs, OH) glucose analyzer was evaluated for abdomen and arm sensors separately, regarding mean absolute relative difference (MARD) and agreement rates (AR) stratified by glucose range and rate of change (RoC). Additionally, clinical accuracy, sensor attachment rate, pain, and safety were assessed. This single-center analysis was developed with the intention to provide European-and particularly German-data. The presented site was the highest-enrolling center in the study and, as such, can be considered representative of the overall study population-an assumption that the analysis confirmed. 20/20 AR and MARD were 95.5% and 9.4% for abdomen sensors, and 95.3% and 9.8% for arm sensors, respectively. Consensus error grid (CEG) analyses revealed that 100% of CGM-comparator pairs fell in zonesA and B for abdomen and arm sensors. Accuracy of sensors remained stable throughout the wearing time. Adhesion rate was 100% for abdomen sensors and 97.1% for arm-worn sensors, without the use of any over-tape during the 15-day study period. Pain during insertion and removal was reported as minimal, and no unexpected safety issues were identified. Data from a single study center showed that the performance of the i3 CGM is comparable to that published for other established CGM devices, and accuracy results were within limits specified for integrated continuous glucose monitoring systems (iCGM). The i3 CGM showed reliability, and its safety was validated during the 15 study days. The study was registered under ClinicalTrials.gov (ID: NCT05806554).

This study evaluates how large language models (LLMs) determine environmental, social, governance (ESG) scores, utilizing retrieval-augmented-generation (RAG) procedures. Three LLMs–Claude-4, ChatGPT-4o, and Gemini-2.5–were used to find the environmental (E), social (S), and governance (G), scores for a total of nine different, publicly traded companies of three different sizes (small, medium, and large) based on market capitalization. The scores of four companies (Morgan Stanley, Goldman Sachs, Berkshire Hathaway, East West Bancorp) were found using one set of prompts, and the other five (BlackRock, PNC, Bank of America, American Financial Group, and GreenDot) were found using a separate set of prompts, utilizing the same criteria and methods with changes in wording. Both sets of prompts, or each trial, found that RAG approaches produce more stable scores that were more consistent with their existing scores found by established rating agencies (Morningstar Sustainalytics, S&P Global, and JUST Capital). These findings suggest that LLMs demonstrate greater consistency in measuring ESG performance when using RAG methods and providing structured data and criteria, exemplifying the growing capabilities and prospective viability for LLM-determined ESG ratings.

Retrospective review of prospectively, consecutively enrolled patients. To assess differences in safety, efficiency and alignment between L-ALIF and LLIF at the L4-5 level in lateral single position surgery (L-SPS). The safety of L4-5 access in lateral lumbar interbody fusion (LLIF) may be limited by psoas, iliac crest and vascular anatomy. Alternatively, lateral decubitus anterior lumbar interbody fusion (L-ALIF) can be used at the L4-5 level during L-SPS. Patients who underwent 1-2 level L-SPS patients including L4-5 were analysed from 7 institutions across 3 countries (Australia, Brazil, USA). Patients were grouped by the L4-5 interbody fusion technique: L-ALIF or LLIF. Demographics, procedural characteristics, complications and sagittal alignment were analysed. Of 511 patients, 72 underwent L4-5 L-ALIF and 439 L4-5 LLIF. L-ALIF patients had more levels fused (1.65 vs.1.25, P<0.001), longer operative time (115.78 vs. 89.08min, P<0.001) and length of stay (LOS) (2.41 vs. 1.71d, P<0.001).Propensity matching for demographics and levels fused (72 per group), demonstrated similar operative time (115.78 vs. 115.77min, P=0.998), LOS (2.41 vs. 1.98d, P=0.069) and blood loss (138.68 vs. 165.00mL, P=0.408).L-ALIF patients had less postoperative (4.2% vs. 21.6%, P<0.001) and minor complications (1.4% vs. 15.0%, P=0.001), mainly attributable to less transient thigh dysaesthesia (0.0% vs. 6.4%, P=0.028). Intraoperative complications (2.8% vs. 2.5%, P=0.892), major postoperative complications (2.8% vs. 8.9%, P=0.077), reoperations within 90-days (2.8% vs. 7.1%, P=0.170) and cage revisions (1.4% vs. 1.6%, P=0.896) were similar.L-ALIF more accurately restored L4-S1 regional lordosis (36.1° vs. 29.7°, P=0.017) postoperatively, and enabled larger improvement in L4-5 segmental lordosis (change of 6.8° vs. 1.8°, P<0.001). L-ALIF at L4-5 is a safe alternative to LLIF in L-SPS. Additionally, L4-5 L-ALIF enables more accurate restoration of L4-S1 lordosis and effectively improves L4-5 segmental lordosis.

This study investigates the causes of mathematics anxiety, its effect on mathematical performance, and the influence of field placement among preservice teachers enrolled in a field-based elementary mathematics methods course. To investigate this, the study utilized four tools: the Abbreviated Mathematics Anxiety Rating Scale (A-MARS), concept maps, Praxis Core test score, and questionnaires. The quantitative analysis indicates a negative correlation between anxiety and math performance. The analysis of concept maps and questionnaires indicate that key contributors to math anxiety include pop-up quizzes, tests, exams, memorization of mathematical ideas, and past negative experiences with school mathematics. The qualitative data analysis revealed that reduced mathematics anxiety during field placements was primarily due to practical teaching experience, constructive feedback, positive student interactions, and opportunities for observation and reflection. Understanding the root causes of mathematics anxiety is essential for supporting preservice teachers and improving their teaching effectiveness. Additionally, field placements play a crucial role in reducing math anxiety by providing hands-on teaching experience and building confidence. It is important to alleviate math anxiety in preservice teachers to have a more positive impact on their future students.

Abstract Soil pH and liming recommendations that address the soils, crops, and liming materials have been developed and adopted by land grant universities since the early 20th century. We inventoried land grant institution soil pH and lime requirement (LR) measurement methods for 1980 and 2020 and examined differences in lime rate recommendations for six reference soils using a survey developed by members of the Fertilizer Recommendation Support Tool initiative. Laboratory analysis for six acidic soils with a range of properties was shared with scientists requesting a lime recommendation for each, assuming a 0‐ to 15‐cm soil depth, 6.5 target pH, and lime material having 100% effective calcium carbonate equivalence. Soil pH methods, LR methods, and lime rate recommendations were documented for 48, 41, and 34 states, respectively. The most widely used pH method was a 1:1 soil–water ratio (34 states, 71%). Thirty‐one states use one or more buffer solutions to determine LR with the most widely used being the Sikora (10 states), Mehlich (10 states), and Shoemaker, McLean, and Pratt (nine states) buffers. Forty lime rate recommendations from 34 states for each soil were summarized with median rates ranging from 2242 to 9079 kg ha −1 and coefficients of variation ranging from 41% to 73%. The reasons for high LR variability are likely due to different calibrations as no strong trends for LR method or region were observed. Efforts are needed to develop and harmonize lime recommendations to provide accurate and transparent guidance, especially for states sharing common soils and boundaries.

ABSTRACT This paper reflects the results from a 3-year quantitative study in higher education on inquiry-based learning (IBL). Utilizing primary data collection in a quasi-experimental survey, we examined the impact of IBL on six cohorts of undergraduate students. We aimed to answer our main research question: Can IBL be an effective pedagogy that helps students develop their key skills, through: (1) exploring how students assessed themselves and their peers on four skills; and (2) comparing student and peer assessments across social work courses utilizing IBL as pedagogy utilizing a social work course taught with traditional methods (non-IBL), and a nonsocial-work course using IBL. We analyzed the quantitative data applying bivariate analysis (paired and independent t-tests) with SPSS. We found that in social work and nonsocial-work courses using IBL as pedagogy, students and their peers identified an increase in the development of their key skills; peer-assessments were consistently higher than self-assessments. Our study reveals that IBL may offer an opportunity to provide authentic learning activities and assessments in social work education to support students’ development of four key skills required for success in higher education.