Water intake is vital for health, yet the determinants of preformed water consumption in adults are poorly understood. This study aimed to apply machine learning (ML) models to identify factors associated with preformed water intake, defined as water ingestion from plain water, other beverages, and food. This secondary analysis used baseline data from 219 participants in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy 2 trial, a randomized controlled trial with extensive measures of body composition, energy expenditure, and dietary, physiological, psychological, and biomarker variables in healthy adults without obesity. Habitual intake of preformed water was quantified using deuterium and oxygen-18 isotope data obtained during 2 consecutive 14-d doubly-labeled water measurement periods of weight stability. We developed models using linear regression, tree-based models (random forest, gradient boosting, and extreme gradient boosting), and penalized regression models (ridge, lasso, and elastic net) to identify factors associated with preformed water intake. On the basis of root mean squared error, the ridge regression model using 25 variables was the best and explained 38% of the variance in preformed water intake. Higher preformed water intake was associated with higher intake of dietary fiber, protein, alcohol, total weight of food ingested, and lower intake of carbohydrate and sodium. Higher preformed water intake was also associated with lower percent body fat and higher fat-free mass and total energy expenditure. Notably, ML models identified alcohol and potassium intake as important predictors that were not selected by traditional linear regression, underscoring their ability to capture nuanced relationships. These results demonstrate that data-driven ML models using a complex dataset can identify features and patterns associated with an important nutrient that might be missed using traditional statistical approaches and could be used to identify individuals at risk of inadequate hydration. This trial was registered as clinicaltrials.gov at NCT00427193.

Bariatric surgery is the most effective intervention for severe obesity, yet the late postoperative period imposes significant challenges, particularly weight regain and nutritional deficiencies. This study, designed as an Integrative Literature Review, aimed to investigate recent clinical evidence (2023-2025) regarding long-term nutritional management for the prevention of these complications. The data search was conducted in the PubMed, SciELO, and LILACS databases. The results demonstrate that the abandonment of interdisciplinary follow-up directly correlates with weight relapse. It was observed that maladaptive eating behaviors, notably grazing, coupled with the failure to meet protein intake targets (≥ 60 g/day), are the main predictors of weight stability loss. The literature reinforces the need for active clinical monitoring, utilizing the percentage of weight regain (%WR) calculation to guide early interventions. It is concluded that the concept of "clinical discharge" must be eliminated for bariatric patients, demanding uninterrupted metabolic and nutritional management to ensure the lifelong efficacy of the procedure.

To investigate the association between energy intake at the initiation of enteral nutrition (EN), subsequent changes in body mass index (BMI), and survival in patients with amyotrophic lateral sclerosis (ALS). This retrospective study included 121 patients with ALS who received EN. Annual BMI decline rates (∆BMI, kg/m2/year) were calculated for three periods: from symptom onset to diagnosis (T1-T2), from diagnosis to EN initiation (T2-T3), and from EN initiation to post-EN assessment (T3-T4). Energy intake per weight (E/W, kcal/kg/day) at EN initiation was also assessed. Survival after EN initiation was analyzed using Kaplan-Meier methods and Cox proportional hazards models. Post-EN BMI decline (∆BMIT3-T4) showed a significant negative correlation with E/W at T3 (p < 0.001). Patients with lower post-EN BMI decline (∆BMI < 0.8kg/m2/year) had significantly longer survival after EN initiation than those with greater BMI decline (p < 0.001). Multivariate Cox analysis identified ∆BMIT3-T4 and pre-EN respiratory decline as independent predictors of post-EN survival. Subgroup analyses demonstrated that patients who maintained body weight after EN had better survival irrespective of energy intake at EN initiation. Weight maintenance following EN was associated with prolonged survival in ALS, whereas energy intake at EN initiation alone was not. These findings suggest that the survival benefit of nutritional intervention may be mediated through stabilization of body weight rather than caloric intake per se.

Cardiometabolic multimorbidity (CMM) is a growing global health challenge. Traditional body mass index (BMI) metrics, such as baseline values or simple change, fail to capture the dynamic nature of long-term weight maintenance. We aimed to evaluate the association between time in target range for BMI (TTR-BMI)-a composite metric of weight stability and magnitude-and the risk of incident CMM and its subtypes in middle-aged and older adults. We conducted a pooled analysis of 9167 participants aged ≥45 years from two prospective cohorts: the China Health and Retirement Longitudinal Study (CHARLS) and the English Longitudinal Study of Ageing (ELSA). A landmark analysis design was employed to minimise immortal time bias. TTR-BMI was calculated via linear interpolation based on cohort-specific normal weight ranges. Multivariable Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CMM, adjusting for sociodemographics, lifestyle factors, baseline BMI, and pre-existing cardiometabolic burden. During the follow-up period, higher TTR-BMI was linearly associated with a lower risk of incident CMM. In fully adjusted models, each 1-SD increase in TTR-BMI was associated with a lower risk of CMM (HR 0.896, 95% CI 0.845-0.950). Compared with participants "never in range" (TTR = 0), those "always in range" (TTR = 1) had a 23.8% lower risk of CMM (HR 0.762, 95% CI 0.669-0.868). Subtype analysis revealed that the inverse association was most pronounced for metabolic-dominant phenotypes, particularly the co-occurrence of diabetes and dyslipidaemia (HR 0.76, 95% CI 0.59-0.98). The associations were robust across cohorts and stronger in men and individuals aged ≥60 years. Higher TTR-BMI is an independent predictor of lower CMM risk in middle-aged and older adults, offering superior prognostic value for metabolic multimorbidity patterns. These findings highlight the clinical importance of prioritising long-term weight maintenance within a target range, rather than single time-point assessments, as a key strategy for delaying the onset of cardiometabolic disease.

This study comparedweight-loss outcomes in patients prescribed tirzepatide by weight-loss status and assessed results among patients transitioning from semaglutide. This retrospective cohort study analyzed 6-month weight-loss outcomes in adults treated with tirzepatide between May 2022 and January 2023. Patients were classified as weight-reduced if they had lost ≥ 10% total body weight (TBW) before starting tirzepatide. Among those who switched from therapeutic semaglutide (≥ 1.7 mg weekly for ≥ 1 month), reasons for switching were categorized as non-response (< 5% weight loss after ≥ 3 months), plateau (≥ 5% loss followed by weight stabilization), or other. Of 941 charts, 293 (31.1%) met inclusion criteria (65% female; mean age 52 years; mean BMI 36.15 kg/m2). Weight-reduced patients (n = 133) lost 7.2% TBW versus 10.3% in non-weight-reduced patients (n = 160; p < 0.001). When analyses were stratified by type 2 diabetes (T2D) status, this difference remained significant among patients without T2D. Sixty-one patients switched from semaglutide due to non-response or plateau and lost 5.3% TBW. Those switching at a plateau (n = 28) lost 8.1% versus 2.9% for non-responders (n = 33; p < 0.001). Tirzepatide produced meaningful weight loss across groups but outcomes varied based on weight-reduction status, T2D status, and prior response to semaglutide.

Metabolic bariatric surgery (MBS) improves fertility in women with severe obesity, raising concerns regarding the optimal timing of conception. Current guidelines recommend postponing pregnancy for 12-24 months after surgery; however, evidence on the impact of the surgery-to-conception interval on pregnancy outcomes remains limited. This retrospective observational cohort study was conducted within a multicenter research framework investigating pregnancy outcomes after MBS. Data from 156 women who conceived after MBS between 2015 and 2024 were collected from eleven accredited bariatric centers. Participants were stratified according to the interval between surgery and conception: <12 months, 12-24 months, and >24 months. Maternal outcomes included gestational diabetes mellitus, pregnancy-induced hypertension, pre-eclampsia, mode of delivery, and gestational weight gain (GWG). Neonatal outcomes comprised gestational age at delivery, birthweight, and Apgar scores. Group comparisons were performed using the Kruskal-Wallis test and Pearson's chi-square test. Among the 156 pregnancies analyzed, 41 occurred within <12 months, 71 within 12-24 months, and 44 after >24 months following surgery. Sleeve gastrectomy was the predominant procedure. No statistically significant differences were observed between groups in maternal complications, mode of delivery, gestational age at birth, birthweight, or Apgar scores (all p > 0.05). Gestational weight gain tended to be lower in pregnancies conceived within 12 months, without reaching statistical significance. The surgery-to-conception interval was not significantly associated with adverse maternal or neonatal outcomes in this cohort. Pregnancy planning after bariatric surgery should be individualized based on postoperative weight stabilization and nutritional status rather than a fixed time threshold; confirmation in larger prospective studies is warranted.

The blending process in raw material yards is essential for maintaining precise material proportions in downstream production, directly influencing product quality and energy efficiency in industries such as steel and coal processing. However, stringent operational constraints, including silo capacity limits, discharge rates, equipment movement delays, and a strict no-empty-silo requirement, result in a strongly coupled, high-dimensional combinatorial scheduling problem. In this paper, we develop a mixed-integer nonlinear programming (MINLP) model to capture the complex dynamics of silo weight and equipment operations. The primary scientific contribution of this work lies in the theoretical discovery of a structural decoupling property within the complex MINLP. We analytically prove that by fixing the replenishment sequence, the intractable global problem can be rigorously decomposed into two subproblems: a linear programming (LP) problem for silo-filling cart scheduling and a shortest-path problem solvable via dynamic programming (DP) for reclaimer scheduling. Leveraging this decomposition, a two-stage metaheuristic algorithm is proposed, combining greedy initialization with multi-round simulated annealing enhanced by local search. Experimental validation using real industrial data demonstrates that the proposed method consistently outperforms the greedy algorithm. Crucially, while the commercial solver Gurobi struggles to converge within a practical 1800 s time limit, our approach yields comparable solution quality in mere seconds. Furthermore, robustness analysis under a 20% demand surge confirms the algorithm’s adaptive capability, maintaining the silo weight stability through re-optimization. This research provides a robust, computationally efficient solution for the blending process in raw material yards.

Background: Massive weight loss (MWL) following bariatric surgery or medical interventions results in significant soft tissue facial changes characterized by accelerated facial aging, fat devolumization, and increased skin laxity (American Society for Metabolic and Bariatric Surgery, 2019; Tan et al., 2022; Jafar et al., 2024; Shrivastava et al., 2008). These anatomical alterations necessitate specialized surgical approaches distinct from conventional facial rejuvenation procedures (Humphrey &amp; Lawrence, 2023; Tay, 2023). Objective: This literature review aims to synthesize current evidence on multi-stage facial plastic surgery in post-bariatric patients, focusing on the sequencing, indications, and techniques for face, neck, brow, and eyelid lifts. Methods: A comprehensive literature review was conducted examining peer-reviewed publications from 2015-2025 in PubMed, Web of Science, Scopus, and other databases. Search terms included "massive weight loss," "facial rejuvenation," "post-bariatric surgery," "facelift," "neck lift," "brow lift," "blepharoplasty," and "sequencing." Studies addressing facial anatomical changes, surgical techniques, outcomes, complications, and staging strategies were included. Results: MWL patients demonstrate distinct facial changes including 88% midface volume loss, 82% platysma band formation, 60% perioral volume loss, and significantly increased neck skin laxity compared to non-MWL patients (Narasimhan et al., 2015; Couto et al., 2015). Extended SMAS facelift with platysmaplasty represents the preferred surgical approach, requiring approximately twice the volume of fat augmentation (22 mL vs. 12 mL) compared to traditional patients (Narasimhan et al., 2015). Current evidence suggests prioritizing face/neck lift as the primary procedure, with staged or concurrent upper facial rejuvenation (brow lift, upper blepharoplasty) based on individual anatomical assessment (Cabbabe, 2016; Narasimhan et al., 2015; Couto et al., 2015). Lower blepharoplasty is often deferred to reduce complication risk (Patrocinio et al., 2015; American Society of Plastic Surgeons, 2024). Patient selection criteria include weight stability for 12-18 months, BMI &lt;30 kg/m², optimization of nutritional status, and realistic expectations (Jafar et al., 2024; Cabbabe, 2016; Handal et al., 2024). Conclusions: Facial rejuvenation in MWL patients requires specialized technical modifications, enhanced volume restoration, and careful procedural sequencing (Jafar et al., 2024; Humphrey &amp; Lawrence, 2023; Narasimhan et al., 2015). A staged approach prioritizing face/neck lift followed by periorbital procedures appears optimal for safety and aesthetic outcomes (Patrocinio et al., 2015; American Society of Plastic Surgeons, 2024). Further prospective research is needed to establish evidence-based sequencing algorithms and long-term outcome data (Jafar et al., 2024; Cabbabe, 2016).

Significant weight loss, achieved through bariatric surgery, anti-obesity pharmacological treatments, or intensive lifestyle modifications, is frequently associated with cutaneous and morphological sequelae leading to dermatological complications, functional limitations, and a significant psychosocial impact. Reconstructive plastic surgery (abdominoplasty/body lift, limb contouring, breast or cervicofacial procedures) improves comfort, body image, and quality of life, but it carries a risk of complications that requires careful patient selection, weight stabilization, and nutritional optimization. Access to care depends on medico-administrative criteria and documentation of functional limitations. Integration into multidisciplinary care pathways aims to ensure efficient and equitable management.

Integrase inhibitors (INSTI) and tenofovir alafenamide (TAF) have been associated with greater weight gain compared to non-nucleoside reverse transcriptase inhibitors (NNRTIs) and tenofovir disoproxil fumarate (TDF), but the effects of an antiretroviral regimen switch on weight are unclear. This 48-week, 3 parallel group, open-label, multicenter, randomized controlled trial (NCT04636437) in people with HIV and obesity on an INSTI (bictegravir, dolutegravir, or raltegravir) with TAF/emtricitabine (FTC) assessed whether switching to the NNRTI doravirine (DOR) with TAF/FTC or TDF/FTC results in weight loss or stabilization. Treatment effects were estimated using linear regression adjusted for sex, race, and entry weight. Of 147 participants randomized, 145 initiated their assigned treatment. At entry, median age was 49 years; BMI was 34.9 kg/m2, and time on INSTI+TAF/FTC was 3.4 years; 49% were female and 53% Black. After 48 weeks, estimated mean change in weight was -0.47% (95% confidence interval [CI]: -2.09,1.14) for the DOR+TAF/FTC arm, -2.73% (-4.22, -1.23) for DOR+TDF/FTC, and -1.84% (-3.37, -0.30) for INSTI+TAF/FTC. Estimated mean difference in weight change at 48 weeks for DOR vs. INSTI (both with TAF/FTC) was 1.36 percentage points (97.5% CI: -1.20,3.92), and -0.89 percentage points (-3.34,1.57) for DOR+TDF/FTC vs. INSTI+TAF/FTC. There was no evidence of variation by sex or race, nor of treatment differences for changes in fasting lipids, insulin resistance, fat mass, or bone mineral density. In people with HIV and obesity, switching from an INSTI+TAF/FTC regimen to DOR/FTC with either TAF or TDF did not produce clinically meaningful differences in weight change or metabolic health after 48 weeks.

Purpose: Cachexia, characterized by involuntary weight loss, muscle wasting, and metabolic dysfunction, is prevalent in advanced cancer and chronic illnesses. Despite its impact, outpatient treatment models in the U.S. remain limited and unstandardized. Here, we aim to describe the structure, implementation, patient characteristics, and real-world clinical trajectories of a multidisciplinary clinic for cancer cache as well as other forms of unintentional weight loss clinic within an academic endocrinology practice. Methods: We conducted a retrospective observational cohort study of 103 patients referred to a single-center unintentional weight loss clinic over five years. Patients received comprehensive assessments (weight trajectory, nutrition status, 5× sit-to-stand test, handgrip strength) and personalized interventions including nutrition counseling, resistance training, and pharmacologic therapies. Results: Among 103 patients (median age 69.7 years; 53% male), 64% had cancer, while 36% were referred for non-malignant causes of weight loss or cachexia. Reduced appetite or food intake was reported in 43%, and functional impairment was common, with low handgrip strength in 47% and impaired 5× sit-to-stand performance in 79% of assessed patients. Systemic abnormalities were frequent, including elevated hs-CRP (57%), elevated neutrophil-to-lymphocyte ratio (43%), and hypoalbuminemia (26%). Among patients with available paired follow-up data, the median rate of weight change shifted from -0.5 kg/month prior to enrollment to 0.0 kg/month three months after the initial visit (p < 0.0001). Five-times sit-to-stand performance improved modestly at three months (p = 0.042), while handgrip strength was unchanged. Half of patients that engaged with the clinic returned for at least follow-up, but there was no identifiable difference between the population of patients that returned versus those that did not. Conclusions: A structured, multidisciplinary unintentional weight loss clinic in an endocrinology setting was associated with stabilization of weight and modest changes in physical function in this single-center cohort among patients who engaged in follow-up. These findings highlight the successful implementation of integrated outpatient care models and provide practice-based context for future interventions and therapeutic evaluations.

We aimed to evaluate whether the use of a custom prosthesis improves static stability and gait symmetry in a dog with a forelimb amputation. This study involved two therapy dogs owned by the same individual, both mixed breeds with similar physical characteristics. Dog with amputation had a full forelimb amputation and had been successfully using a prosthesis since 2022. Healthy dog served as a control in three different assessment methods evaluating prosthetic effectiveness. For static measurements, a four-scale method and a force plate were used; dynamic data were collected using a pressure-sensor mat. Dog with amputation distributed 21 % of its body weight onto the prosthesis, reducing the load on the contralateral limb from 49 % to 35 %. The total forelimb load increased from 49 % to 56 % with the prosthesis. Stabilometric analysis indicated improved stability with the prosthesis: significant reduction in sway path length, while changes in directional sway components and sway area were not statistically conclusive. Sensor-mat measurements on GAITRite showed that forelimb amputation substantially reduced step length (21.1 cm) and stride length (42.4 cm) on the amputated side, and increased traversal time to 2.4 s, reflecting pronounced gait asymmetry and impaired limb function. The use of a prosthesis improved step length (35.0 and 30.1 cm) and stride length (64.1 and 63.0 cm), and decreased traversal time to 2.2 s, indicating enhanced gait efficiency, although values did not fully reach those of the healthy dog (step length 46.8/44.6 cm; stride length 93.5/87.7 cm; time 1.5 s). These results demonstrate the functional benefits of prosthetic use in canine forelimb amputation.

As a semibiobased copolyamide with outstanding environmental sustainability, polyamide 5T/56 (PA5T/56) blends the excellent processability of aliphatic polyamide 56 (PA56) with the remarkable thermal stability of fully aromatic polyamide 5T (PA5T), thereby substantially enhancing its potential industrial applications. However, its multifunctional performance is critically dependent on crystallization behavior, where hydrogen-bonding interactions serve as the primary thermodynamic driver. This study systematically investigated water-mediated crystallization control in PA5T/56 by regulating initial water content during polymerization. Comprehensive characterization revealed a relationship between water content and key material parameters: lower initial water content enhanced hydrogen bond strength, molecular weight, and thermal stability, while reducing crystallization activation energy. The experimental results revealed that water content systematically modulated hydrogen bond architecture. This control mechanism directly governs crystallization kinetics and final properties, enabling process optimization in PA5T/56 manufacturing.

Full-waveform inversion (FWI) imaging is a high-resolution seismic imaging technique that directly produces subsurface images by inverting the full recorded wavefield. However, its reliability is often limited by numerical dispersion errors arising from finite-difference (FD) forward modeling. One key approach for reducing dispersion is to optimize the FD coefficients using an optimization algorithm. However, conventional methods for optimizing FD weights focus only on reducing spatial dispersion, which can weaken numerical stability, especially when using large time steps (i.e., high Courant&amp;ndash;Friedrichs&amp;ndash;Lewy [CFL] numbers). To address this issue, we introduce a new optimization approach that improves both simulation accuracy and stability. The proposed method combines error functions from both the time&amp;ndash;space domain and the spatial domain into a single adaptive objective function. A dynamic weighting factor, which depends on the CFL number, facilitates a trade-off between accuracy and stability of the optimal FD weights. We also use the seismic wavelet spectrum as prior information to constrain the optimization. The optimization problem is solved by the least-squares method. In the theoretical test, the proposed weights significantly reduce wavefield simulation errors across a wide range of wavenumbers, with a higher CFL number than conventional approaches. When applied to FWI, this method reduces phase distortion and local minima in the objective function. In a test using the Marmousi model at 40 Hz, our approach produced clear and continuous deep structures, closely matching results from dispersion-free benchmarks. In contrast, conventional methods failed due to severe dispersion. This work provides a more robust numerical foundation for high-frequency FWI imaging by improving both accuracy and stability.

Gastroesophageal reflux disease (GERD) affects 20%-30% of patients after sleeve gastrectomy (SG). In patients with a body mass index (BMI) <30 kg/m2, the optimal surgical approach-magnetic sphincter augmentation (MSA) or conversion to Roux-en-Y gastric bypass (RYGB)-remains unclear. We retrospectively compared outcomes of MSA (n = 20) and RYGB (n = 25) in patients with BMI <30 kg/m2 and refractory post-SG GERD at King Abdulaziz University Hospital (2019-2024). Inclusion required objective evidence of GERD despite ≥6 months of optimized proton pump inhibitor therapy. The primary outcome was GERD resolution. Secondary outcomes included proton pump inhibitor cessation, complications, weight trajectory, and diabetes remission at a minimum follow-up of 18 months. GERD resolution occurred in 70% of patients who underwent MSA and 85% of those who underwent RYGB. Proton pump inhibitor cessation rates were 65% and 80%, with lower postoperative GERD-health-related quality of life (HRQL) scores in the RYGB group. Early dysphagia was more common after MSA (30% vs. 4%). MSA was associated with weight stability, whereas RYGB resulted in significant weight reduction. Diabetes remission occurred in 75% of patients, who underwent RYGB. Both procedures effectively managed post-SG GERD in patients with low BMI. MSA offers weight-neutral reflux control, shorter operative time, and no supplementation requirements. RYGB provides superior symptom control and metabolic benefits, including diabetes remission.

Dumping syndrome (DS) and recurrent weight gain are among the most relevant long-term challenges following Roux-en-Y gastric bypass (RYGB). Several treatment strategies have been proposed, including pouch resizing with ring augmentation (PRRA). This study presents long-term outcomes of PRRA, with a focus on weight trajectory and the management of DS symptoms. A retrospective analysis of all PRRA procedures performed at a tertiary referral center between January 2008 and September 2023. Clinical data were obtained from electronic health records and patient questionnaires. Sixty-two patients (90.3 % female, mean age at time of RYGB 40.2 ± 9.5 years, mean BMI 47.4 ± 7.9 kg/m2) underwent PRRA at a mean interval of 56.3 ± 34.6 months after RYGB. DS was the leading indication (74.2 %), followed by recurrent weight gain (24.2 %) and primary suboptimal clinical response (1.6%). Following PRRA, 62.8 % of patients (n = 45) reported long-term improvement in DS-related symptoms, and 79 % (n = 57) achieved renewed weight loss. Long-term weight stabilization was observed, with only modest recurrent weight gain (+2.1± 5.4 kg/m2from post-PRRA nadir weight) after a mean follow-up of 48.6± 40.0 months. Ring removal was required in 25.8 % of patients, predominantly due to dysphagia and regurgitation. PRRA is an effective revisional option for managing DS symptoms after RYGB and contributes to sustained weight stability in patients with recurrent weight gain. However, ring-related adverse effects may necessitate removal in a subset of patients. PRRA reduces dumping syndrome severity and frequency long term. PRRA supports renewed weight loss and long-term stability after RYGB weight regain. Ring retention is high; despite adverse effects overall tolerability is favorable. PRRA is a reversible revisional option with sustained clinical effectiveness.

Abstract: According to OMIM and Orphanet databases, Schaaf-Yang syndrome (SYS) (OMIM: 615547, ORPHA: 398069) is a rare genetic disorder that shares certain clinical features with Prader-Willi syndrome (PWS), including hypotonia, developmental delay, and early-onset obesity. However, SYS often exhibits a more complex and variable phenotype. Missense variants in MAGEL2 have been reported only rarely, and their phenotypic spectrum appears milder and more variable than that of truncating mutations. Data on early-onset obesity as a dominant feature in such patients are limited. In this case report, we describe a child with mild phenotype (SYS) carrying the novel missense variant MAGEL2(NM_019066.5) :c.1265C>T (p.Pro422Leu) presenting with severe early-onset obesity and a comparatively neurodevelopmental phenotype. We present a case of a boy with neonatal hypotonia, diagnosed with (SYS) at age 9 years, with follow-up to age 11 years. The boy was born at 34+3 weeks of gestation with hypotonia, feeding difficulties, and a persistent ductus arteriosus that required surgical ligation in early infancy. In the following years, he developed severe early-onset obesity, already evident by age 2 despite multidisciplinary care. Genetic testing performed at age 9 years identified a novel missense variant (NM_019066.5)c.1265C>T in the MAGEL2 gene, which was not inherited from his mother, thereby confirming the diagnosis of (SYS). At the time of the most recent evaluation, at age 11 years, he remained under long-term follow-up. Clinical management over this period included endocrine therapy, cardiac surgery, physical rehabilitation, and dietary interventions, and despite the complexity of his condition, long-term stabilization of his BMI percentile was achieved with consistent non-pharmacological interventions. This case highlights the importance of early multidisciplinary investigation and intervention in SYS, particularly when obesity is the dominant feature. Effective long-term weight stabilization is possible through structured lifestyle management. Keywords: Schaaf-Yang syndrome, pediatric obesity, MAGEL2 mutation, hypothyroidism, developmental delay, physical activity

Abstract Objective: To evaluate the impact of GLP-1R/GIPR/GCGR agonist-associated weight loss on breast cancer (BC) risk and tumor progression. Background: BC is the second leading cause of cancer death among women in the US. Obesity increases the risk of multiple cancers, including BC. Previous pre-clinical studies demonstrated that GLP-1 receptor agonists promote weight loss, improve metabolic dysfunction, reduce cancer risk and blunt progression in pancreatic and lung cancer, but effects on spontaneous BC were unknown. Hypothesis: To assess the impact of a novel triple incretin receptor agonist (TIRA) on BC risk and tumor progression in mice with obesity-associated metabolic dysfunction. Methods and Approach: Female FVB C3(1)-T antigen (“C3Tag”) mice, a genetically engineered mouse model (GEMM), which develop BC spontaneously, were utilized to evaluate effects of medical weight loss on tumor risk and outcomes. Overweight mice were subjected to: 1) vehicle (VEH) control to maintain body weight; 2) TIRA as weight loss intervention; or 3) caloric restriction to allow for weight matched (WM) controls. Mice were fed a high-fat diet from 8 weeks of age. After gaining weight, they received subcutaneous TIRA (15 nmol/kg) or vehicle every other day. One group was sacrificed at 15 weeks to investigate preneoplastic lesions in the mammary gland. The second group was allowed to proceed to endpoint to examine tumor latency, progression, and survival. N=10-12 per group. Gut microbiome and circulating mediators were quantified by proteomics and metabolomics. One way ANOVA was used. Results: TIRA and WM induced significant body weight loss (∼15-20%) within 2-3 weeks, followed by weight stabilization, with reduced circulating leptin concentration compared to VEH. TIRA and WM also reduced 4-hour fasting blood glucose, decreased gonadal white adipose tissue, and mammary fat pad mass. Moderately reduced muscle mass was observed in TIRA and WM mice in the preneoplasia group but not in the long-term survival group. TIRA delayed gastric emptying revealed by higher cecal contents compared to VEH and WM in the preneoplasia group. TIRA-induced ceramide, metabolite, and microbiome changes were evident. In the survival group, TIRA significantly delayed tumor latency compared to VEH. Conclusion: TIRA and WM effectively induced weight loss and improved metabolic dysfunction with both interventions demonstrating significantly reduced adiposity, hyperglycemia, and tumor-promoting adipokines. TIRA-associated weight loss significantly delayed tumor onset whereas WM did not, suggesting a TIRA-specific anti-tumor effect. Results demonstrate that pharmacological weight loss suppressed early tumor progression - despite being in a transgenically driven GEMM - and improved outcomes in obesity-associated BC. Citation Format: N. Pervaiz, S. J. Marathe, Z. Powell, L. G. McGrath, Z. T. Mustafa, L. Wang, M. C. Playdon, S. A. Summers, J. Hao, B. Li, J. F. Pierre, L. Makowski. Triple incretin receptor agonist induced weight loss delays tumor latency in obesity-associated breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-05-26.

We aimed to develop an individual-level metric called "Waist Circumference Time in Target Range" (WC-TTR), determine its optimal target range for predicting Type 2 diabetes (T2DM) incidence, and assess its association with the risk of developing T2DM. A total of 5,693 adults from the Tehran Lipid and Glucose Study (TLGS) were included in the analysis. WC-TTR was calculated over a 9-year period of waist circumference assessments, and incident T2DM was ascertained during the subsequent 9 years. In this study, the target range was determined using a novel approach based on Dynamic Time-dependent ROC analysis to identify the optimal target range. The association between WC-TTR and incident T2DM was evaluated using multivariable Cox proportional hazards models incorporating a restricted cubic spline function. During the follow-up period, 684 participants developed T2DM. Each 1 standard deviation (SD) increase in WC-TTR was associated with a 36% reduction in the risk of developing T2DM (hazard ratio (HR): 0.67; 95% CI: 0.59-0.77). In obese individuals, a 1 SD increase in WC-TTR correlated with a 48% reduction in T2DM risk (HR: 0.52; 95% CI: 0.40-0.96), which was also statistically significant. Our study introduces "WC-TTR" as a preventive strategy for T2DM. Maintaining WC within the range of 65 to 97 centimeters for ten years significantly lowers the risk of T2DM, particularly in individuals with obesity. Additionally, we emphasized the importance of this metric in monitoring weight stability, which can enhance personalized care and prevention strategies for T2DM and related health conditions. The online version contains supplementary material available at 10.1007/s40200-026-01869-9.

Quantitative asset allocation remains a critical challenge in modern finance, particularly due to the inherent uncertainty of expected returns (μ) and the sensitivity of portfolio outcomes to the stability of portfolio weights. This study conducts a comparative empirical analysis of three portfolio strategies—MVO, Static RP, and Dynamic RP—using a long-only portfolio of eleven highly liquid assets, consisting of U.S. large-cap equities and gold, over the period 2015–2025. Results from historical backtesting indicate maintaining a competitive Sharpe ratio (1.418) and the lowest Maximum Drawdown (−0.2770) relative to Markowitz MVO (−0.3120) and Static RP (−0.2788). Although Markowitz delivers the numerically highest Sharpe ratio (1.655), this advantage is largely driven by in-sample optimization, with limited robustness under realistic implementation settings. In contrast, Dynamic RP demonstrates superior downside risk management, weight stability, and adaptability to changing market conditions, suggesting a more practical and resilient framework for real-world investment applications. Overall, the findings indicate that Dynamic Risk Parity provides an effective and robust alternative to traditional mean-variance optimization, offering investors a strategy that balances return potential, risk mitigation, and portfolio stability, while addressing key limitations of classical MVO approaches.