Patients with heavily calcified coronary arteries represent a challenge in percutaneous coronary intervention (PCI), as severe calcification impairs device delivery and limits optimal stent expansion, leading to higher risks of stent thrombosis, restenosis, and adverse clinical outcomes. Approximately 20% of patients undergoing PCI exhibit severe coronary calcification, which independently predicts incomplete revascularization, increased mortality, and higher rates of major adverse cardiovascular events over mid-term follow-up. Recent advances have focused on improving the assessment and management of calcified lesions. Intracoronary imaging modalities, including intravascular ultrasound and optical coherence tomography, allow precise detection and characterization of calcium burden, overcoming the limitations of angiography. These tools play a pivotal role in guiding procedural strategy, enabling tailored selection of calcium-modifying techniques based on lesion morphology, and optimizing stent deployment. Technological innovations have significantly expanded therapeutic options. While non-compliant balloon angioplasty alone is often insufficient, adjunctive devices such as cutting and scoring balloons improve plaque modification in focal disease. Atherectomy techniques, including rotational and orbital systems, are effective for more complex lesions but require technical expertise and carry procedural risks. Intravascular lithotripsy has emerged as a promising, less aggressive modality capable of fracturing deep calcium, while excimer laser atherectomy offers an alternative for resistant lesions. Despite these advances, current evidence supporting calcium-modifying strategies is largely based on procedural outcomes rather than definitive improvements in long-term clinical endpoints. Meta-analyses and randomized trials have not demonstrated clear superiority of any single technique, and most studies remain underpowered. Intriguingly, recent data suggest that outcomes in treated calcified lesions may approximate those of non-calcified disease, raising the hypothesis that these technologies could mitigate the adverse impact of calcification. However, this remains unproven, highlighting the urgent need for adequately powered randomized trials to determine their true clinical benefit.

Alcohol use disorder accounts for 5% of deaths worldwide annually, and there is an urgent need for new therapeutic interventions. Preclinical and initial human studies indicate that the GLP-1 receptor agonist semaglutide might reduce alcohol drinking. This study evaluated the efficacy of semaglutide once-weekly in treatment-seeking patients with alcohol use disorder and comorbid obesity.

In a 26-week, single-centre, randomised, double-blinded, placebo-controlled trial, treatment-seeking participants with moderate to severe alcohol use disorder and comorbid obesity were assigned (1:1) to receive once-weekly semaglutide (2·4 mg subcutaneously) or placebo (saline subcutaneously), in addition to standard cognitive behavioural therapy. The primary endpoint was a reduction in the number of heavy drinking days assessed after 26 weeks of intervention, analysed with an ANCOVA model. Analysis adhered to the intention-to-treat principle, and missing outcome data were addressed using multiple imputations. Safety was assessed in all treated patients. The trial is registered at ClinicalTrials.govNCT05895643, and is complete.

From June 10, 2023, to Feb 4, 2025, 108 participants (53 women and 55 men) were enrolled, with 54 participants in each of the semaglutide and placebo treatment groups, and all were included in the data analysis. Overall, 88 participants (81%) completed the full intervention. Semaglutide was associated with a reduction in heavy drinking days (-41·1 percentage points from baseline, 95% CI -48·7 to -33·5) compared with placebo (-26·4, -34·1 to -18·6; estimated treatment difference -13·7 percentage points, -22·0 to -5·4; p=0·0015), and had substantial effects on multiple secondary alcohol-related and somatic outcomes. Adverse events were transient, generally mild to moderate gastrointestinal effects, and occurred more frequently in the semaglutide group.

Semaglutide showed robust therapeutic effects in treatment-seeking participants with obesity and alcohol use disorder and this trial supports previous preclinical and clinical findings suggesting GLP-1 receptor agonists as a potential novel treatment target for alcohol use disorder.

The Research Foundation, Mental Health Services (Capital Region of Denmark), the Novo Nordisk Foundation, the Novavi Foundation, the Hartmann Foundation, and the Augustinus Foundation.

The present study provides a comprehensive introduction to the features of histone tails, including their length, subtypes, nomenclature, biological functions, and regulation, and systematically reviews their roles in psychiatric disorders. A literature search was conducted, covering over 200 common histone modifications and the top 20 common psychiatric disorders. The results indicate that 26 histone tail modifications are positively associated with ten psychiatric disorders, with most located at H3 and H4 tails, and only one at the H2AX tail. All modifications occur at lysines (K), except for two at arginine (R) or serine (S). The top five modifications associated with psychiatric disorders are H3K9ac, H3K4me3, H3K27ac, H3K9me2, and γH2AX. The majority of the studies (92%) report substance use disorders, Alzheimer's disease, major depressive disorder, schizophrenia, and autism spectrum disorders as the top five psychiatric disorders associated with histone tail modifications. In conclusion, histone tail modifications play crucial roles in various psychiatric disorders, and targeting them and associated epigenetic regulators may offer potential therapeutic strategies for treating psychiatric disorders by providing new insights into the molecular mechanisms underlying abnormal gene expression.

Meeting the needs of autistic children requires the effective implementation of evidence-based interventions (EBIs). The TEAMS project tested the effectiveness of leader-level and provider-level implementation strategies to support the implementation of two autism-focused EBIs. The leader-level strategy was found effective in improving observed provider fidelity and standardized caregiver-reported child outcomes. This study extends the primary trial findings by assessing individualized child outcomes.

The current study examines the individual and combined effects of the TEAMS implementation strategies - TEAMS Leadership Institute (TLI) and TEAMS Individualized Provider Strategy (TIPS) - on caregiver-identified Top Problems.

Data were extracted from the TEAMS project, a hybrid type 3 implementation-effectiveness trial testing the effects of implementation strategies when paired with AIM HI (An Individualized Mental Health Intervention for Autism) in mental health programs (Study 1) and CPRT (Classroom Pivotal Response Teaching) in classrooms (Study 2). Programs/districts were randomized to TLI and/or TIPS. Data from 353 caregivers of autistic children (M _age = 7.89 years, SD = 2.92, 80.1% male, 44.2% Latinx) were analyzed. Clinical outcomes were measured using the Top Problems Assessment at intake and after 6 months.

Controlling for study intervention (AIM HI or CPRT), a significant TLI x Time interaction (B = -0.95, p = .021) indicated greater reductions in Top Problem intensity in the TLI (vs. no-TLI) condition. No significant effects were found for TIPS or TIPSxTLI.

Findings support the effectiveness of leader-focused implementation strategies in improving the outcomes valued most by families.

Depression is a common illness that affects people within every society around the world. It afflicts the young and the old and everyone in between, and as such poses an immense global burden. New interventions and a deeper understanding of this illness are emerging, but improving the use of existing treatments is equally important and might be a more efficient and effective strategy to addressing depression. Therefore, it is imperative that we improve the diagnosis of depression and its clinical management.

Molecular testing has emerged as a pivotal tool for the preoperative assessment of cytologically indeterminate thyroid nodules. In this cross-sectional study, we evaluated the diagnostic utility of a targeted next-generation sequencing (NGS) 4-gene panel, including BRAF^V600E, TERT promoter mutations, RET fusions, and NTRK3 fusion, for enhancing the cytological diagnosis of thyroid nodules prior to surgical intervention. A total of 827 thyroid nodules subjected to fine-needle aspiration and subsequent histopathological confirmation were analyzed, among which 773 (93.5%) were classified as malignant or noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). The observed prevalence of molecular alterations was: BRAF^V600E, 68.3% (526/770); TERT promoter mutations, 10.3% (79/770); RET fusions, 10.3% (79/770); and NTRK3 fusion, 3.9% (30/770). Notably, the 4-gene NGS panel demonstrated brilliant diagnostic performance for indeterminate cytological nodules (Bethesda categories III-V), achieving a sensitivity of 87.9%, specificity of 96.3%, positive predictive value (PPV) of 99.7%, negative predictive value (NPV) of 35.9%, and overall accuracy of 88.2%. These findings indicate that the targeted NGS 4-gene panel provides high diagnostic precision in distinguishing benign from malignant nodules. Its implementation offers a cost-effective, efficient molecular diagnostic strategy that may reduce unnecessary diagnostic procedures and facilitate optimized clinical management.

Minimal residual disease (MRD) negativity is a well-established prognostic marker in multiple myeloma (MM), yet the clinical relevance of MRD response timing and duration remains unclear, particularly in real-world settings. We retrospectively analyzed 1048 newly diagnosed MM patients from the National Longitudinal Cohort of Hematological Diseases in China (NICHE) between 2012 and 2023, with a total of 5406 MRD assessments. A longer time to best MRD response (> 6 months) was significantly associated with improved progression-free and overall survival, especially among those with persistent MRD positivity but stable low-level disease burden. Early responders were more likely to exhibit high tumor burden and high-risk cytogenetic abnormalities. Notably, a prolonged MRD duration (≥ 36 months) predicted favorable outcomes regardless of MRD negativity status. Integrating response timing and duration identified a "Late + Durable" MRD pattern consistently associated with the best prognosis, even in patients with persistent MRD positivity, high-risk cytogenetics, or without ASCT. These findings highlight the prognostic significance of longitudinal MRD monitoring beyond single-timepoint assessments. A slow but durable MRD response may overcome adverse biological features and support individualized risk stratification, therapeutic decisions, and long-term disease monitoring in MM.

Plant based protein consumption is increasingly recognized for its therapeutic potential in managing metabolic health and preventing chronic diseases. This review provides a comprehensive analysis of the physiological impact of plant proteins, including their roles in satiety regulation and weight management via the modulation of appetite regulating hormones. We examine how plant proteins optimize lipid metabolism and reinforce gut homeostasis by promoting diverse microbiota and increasing the production of short chain fatty acids. Furthermore, we dissect the mechanisms through which plant proteins and their digestion derived peptides attenuate the pathogenesis of cardiovascular disease, type 2 diabetes, and chronic kidney disease. Specific attention is given to the modulation of intracellular signaling pathways such as PI3K-Akt and the regulation of the renin angiotensin system. The review also highlights that the health efficacy of plant proteins is highly dependent on the food matrix, where synergistic interactions between proteins, fiber, and phytochemicals are critical. Finally, the impact of food processing on peptide bioaccessibility is examined, and a process-matrix function paradigm is proposed for future research. In conclusion, these insights underscore the role of plant proteins as functional components that are essential for developing sustainable and precise nutritional strategies to mitigate the global burden of non-communicable diseases.

Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease and end-stage kidney failure worldwide. Genetic factors contribute to inter-individual and population-specific susceptibility to DKD. Data from South Indian populations are limited, highlighting the need for region-specific genetic association studies in DKD.

This case-control study included 125 South Indian individuals: 60 patients with diabetes and proteinuria (DKD), 34 patients with diabetes without kidney disease, and 31 healthy controls. Genomic DNA was isolated and nine variants were genotyped using amplification refractory mutation system polymerase chain reaction (ARMS-PCR). Variant frequencies were compared among groups. In-silico pathogenicity prediction tools and Odds ratio (OR) with 95% confidence intervals (CIs) were estimated using multivariable logistic regression analyses were used to assess the association between genetic variants and DKD risk. Data visualization was performed using R statistical software. Among the nine variants analyzed, the TRPC6 rs36111323 (G > A; p.A404V) was independently associated with DKD (OR = 2.76; 95% CI = 1.04-7.34; p = 0.0418). This variant was more frequent in patients with DKD compared with diabetic patients without nephropathy and healthy controls. Pathogenicity prediction analyses supported a potentially deleterious effect of the variant.

The TRPC6 rs36111323 variant appears to be associated with increased susceptibility to diabetic kidney disease in a South Indian population, suggesting a population-specific genetic risk factor. Validation in larger cohorts and functional studies is warranted to clarify its role and potential application in precision nephrology.

Diabetes mellitus presents a growing public health challenge across geographies including Asia, particularly in countries where blood glucose monitoring (BGM)-referring to capillary finger-prick self-monitoring of blood glucose (SMBG) using a meter and test strips-is underutilized. Having evolved and improved over recent decades, glucose monitoring (GM)-including SMBG and continuous glucose monitoring (CGM)-has become an essential tool for effective diabetes management, yet remains underutilized because of systemic, economic, and educational barriers. This work synthesizes expert insights and published evidence to develop best practice recommendations for BGM.

A targeted literature review (TLR) was conducted across five thematic domains: monitoring practices, clinical decision-making, patient engagement and adherence, technology and innovation, and policy and reimbursement. Insights were complemented by a structured expert forum involving clinicians from seven Asian countries, underscoring larger implications in geographies where SMBG remains underutilized within the diabetes care continuum. The forum highlighted disparities in device access, affordability, and insurance coverage, and emphasized the need for structured diabetes self-management education (DSME) and digital integration.

Findings support the use of structured SMBG for non-insulin-treated type 2 diabetes and CGM for insulin-treated individuals and those at risk of hypoglycemia. Evidence from the literature review also highlighted the importance of proper SMBG technique, with common errors such as inadequate handwashing, repeated lancet use, and excessive finger squeezing contributing to inaccurate readings and finger-site injuries. Hybrid models combining CGM and SMBG for calibration or confirmation are pragmatic solutions balancing clinical utility and affordability. Digital platforms, AI-driven analytics, and mobile apps enhance patient engagement and glycemic control but face challenges of scalability and regulation.

Policy reforms, including inclusion of BGM in national health benefit packages, expanded insurance coverage, and public-private partnerships, are critical to improving access. The recommendations advocate for personalized, context-specific monitoring strategies that balance clinical efficacy with affordability and infrastructure realities. This consensus-based framework aims to guide healthcare professionals in optimizing BGM practices and improving long-term outcomes for people living with diabetes. FITTER BiG is a new extension of the long-standing FITTER initiative, which has provided insulin injection technique recommendations for more than two decades. FITTER BiG complements this work by focusing specifically on best practice recommendations for blood glucose monitoring. FITTER BiG will provide BGM-specific recommendations designed to complement the injection technique guidance outlined in the FITTER Forward consensus statement (Klonoff et al. Mayo Clin Proc 100:682-699, 2025 [1]).