International Expert-Based Consensus Definition, Classification Criteria, and Minimum Data Elements for Osteoradionecrosis of the Jaw: An Inter-Disciplinary Modified Delphi Study.

Purpose: Osteoradionecrosis of the jaw (ORNJ) is a severe iatrogenic disease characterized by bone death after radiation therapy (RT) to the head and neck. With over 9 published definitions and at least 16 classification systems, the true incidence and severity of ORNJ are obscured by lack of a standard for disease definition and severity assessment, leading to inaccurate estimation of incidence, reporting ambiguity, and likely under-diagnosis worldwide. This study aimed to achieve consensus on an explicit definition and phenotype of ORNJ and related precursor states through data standardization to facilitate effective diagnosis, monitoring, and multidisciplinary management of ORNJ.

Pembrolizumab with or without bevacizumab in platinum-resistant recurrent or metastatic nasopharyngeal carcinoma: a randomised, open-label, phase 2 trial.

Background: Vascular endothelial growth factor (VEGF) is overexpressed in nasopharyngeal carcinoma and suppresses the anti-tumour immune response. Previous studies have shown that adding anti-VEGF treatment to PD-1 inhibition treatment strategies improves tumour response. We aimed to compare the efficacy of pembrolizumab, a PD-1 inhibitor, with or without bevacizumab, a VEGF inhibitor, in nasopharyngeal carcinoma.

Tucatinib and trastuzumab in HER2-mutated metastatic breast cancer: a phase 2 basket trial.

Human epidermal growth factor receptor 2 (HER2, also known as ERBB2) signaling promotes cell growth and differentiation, and is overexpressed in several tumor types, including breast, gastric and colorectal cancer. HER2-targeted therapies have shown clinical activity against these tumor types, resulting in regulatory approvals. However, the efficacy of HER2 therapies in tumors with HER2 mutations has not been widely investigated.

Proteomic dataset of sorghum leaf and root responses to single and combined drought and heat stress.

Drought and heat stress significantly limit crop growth and productivity. Their simultaneous occurrence, as often observed in summer crops, leads to larger yield losses. Sorghum is well adapted to dry and hot conditions.

Discordance, accuracy and reproducibility study of pathologists' diagnosis of melanoma and melanocytic tumors.

Accurate melanoma diagnosis is crucial for patient outcomes and reliability of AI diagnostic tools. We assess interrater variability among eight expert pathologists reviewing histopathological images and clinical metadata of 792 melanoma-suspicious lesions prospectively collected at eight German hospitals. Moreover, we provide access to the largest panel-validated dataset featuring dermoscopic and histopathological images with metadata.

Phase I study of BMS-986299, an NLRP3 agonist, as monotherapy and in combination with nivolumab and ipilimumab in patients with advanced solid tumors.

Purpose: BMS-986299 is a first-in-class, NOD-, LRR-, and pyrin-domain containing-3 (NLRP3) inflammasome agonist enhancing adaptive immune and T-cell memory responses.

Materials And Methods: This was a phase-I (NCT03444753) study that assessed the safety and tolerability of intra-tumoral BMS-986299 monotherapy (part 1A) and in combination (part 1B) with nivolumab, and ipilimumab in advanced solid tumors. Reported here are single-center results.

Role of the International Society of Liquid Biopsy (ISLB) in establishing quality control frameworks for clinical integration.

Liquid biopsy (LB) has revolutionized molecular pathology, offering non-invasive insights into tumor biology. However, widespread adoption is hindered by a lack of standardized protocols, requiring robust quality control and harmonized workflows. Large-scale studies are needed to establish effective standard operating procedures (SOPs), particularly for circulating tumor DNA (ctDNA) assays tailored to different disease stages.

Real-world ePRO use and clinical outcomes using electronic patient-reported symptom monitoring for patients with advanced non-small-cell lung cancer receiving first-line pembrolizumab.

This ambispective observational study assessed the impact of Noona, an electronic patient-reported outcomes (ePRO) platform, for patients with non-small cell lung cancer (NSCLC) treated in a community oncology setting. Adults with advanced NSCLC, ECOG performance status of 0-2, who received first-line (1L) pembrolizumab (monotherapy or with chemotherapy) were eligible. Those initiating pembrolizumab from 1 July 2017 to 30 June 2019, identified retrospectively (historical cohort), were compared with those initiating pembrolizumab from 1 October 2019 to 30 September 2021 who were prospectively offered Noona (standard of care [SoC] cohort).

Olaparib as treatment for platinum-sensitive relapsed ovarian cancer by BRCA mutation and homologous recombination deficiency: Phase 2 LIGHT study final overall survival analysis.

Background: LIGHT (oLaparib In HRD-Grouped Tumor types; NCT02983799) prospectively evaluated olaparib treatment in patients with platinum-sensitive relapsed ovarian cancer (PSROC) assigned to cohorts by known BRCA mutation (BRCAm) and homologous recombination deficiency (HRD) status: germline BRCAm (gBRCAm), somatic BRCAm (sBRCAm), HRD-positive non-BRCAm, and HRD-negative. At the primary analysis, olaparib treatment demonstrated activity across all cohorts, with greatest efficacy in terms of objective response rate and progression-free survival observed in the g/sBRCAm cohorts. The authors report final overall survival (OS).

PREVENT and Pooled Cohort Equations in Mortality Risk Prediction: National Health and Nutrition Examination Survey.

Background: The Predicting Risk of CVD Events (PREVENT) equations were developed to address limitations of the Pooled Cohort Equations (PCEs) in predicting atherosclerotic cardiovascular disease (ASCVD) risk. The comparative effectiveness of the PREVENT equations versus the PCEs in predicting mortality risk remains unknown.

Objectives: The purpose of this study was to compare the risk discrimination value of the PREVENT equations with the PCEs for predicting mortality.

The potential role of tumor deposits in the prognosis and TNM staging for colorectal cancer.

Background: Tumor deposits (TDs) can impact proper staging of cancer, which is crucial for discussing prognosis and determining the appropriate treatment plan. Our study aimed to correlate how TDs influence prognosis of resected colorectal cancer (CRC) and how to optimize tumor-node-metastasis (TNM) staging with respect to TDs for clinical decision-making.

Methods: A retrospective analysis was performed on 611 patients with CRC treated in Jiangsu Cancer Hospital from January 1, 2010 to December 31, 2020 among whom 197 had TDs.

Daratumumab plus lenalidomide/dexamethasone in untreated multiple myeloma: analysis of key subgroups of the MAIA study.

In the MAIA study (median follow-up, 56.2 months), daratumumab plus lenalidomide and dexamethasone (D-Rd) significantly improved progression-free survival (PFS) and overall survival versus lenalidomide and dexamethasone (Rd) alone in transplant-ineligible newly diagnosed multiple myeloma (NDMM). In this post hoc analysis of clinically important subgroups in MAIA (median follow-up, 64.

GestaltGAN: synthetic photorealistic portraits of individuals with rare genetic disorders.

The facial gestalt (overall facial morphology) is a characteristic clinical feature in many genetic disorders that is often essential for suspecting and establishing a specific diagnosis. Therefore, publishing images of individuals affected by pathogenic variants in disease-associated genes has been an important part of scientific communication. Furthermore, medical imaging data is also crucial for teaching and training deep-learning models such as GestaltMatcher.

Initial Decline in Glomerular Filtration Rate With Finerenone in HFmrEF/HFpEF: A Prespecified Analysis of FINEARTS-HF.

Background: An initial decline in estimated glomerular filtration rate (eGFR) often leads to reluctance to continue life-saving therapies in patients with heart failure (HF).

Objectives: The goal of this study was to describe the association between initial decline in eGFR and subsequent clinical outcomes in patients randomized to placebo or finerenone.

Methods: In this prespecified analysis of FINEARTS-HF (Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients with Heart Failure), we examined the association between initial decline in eGFR (≥15%) from randomization to 1 month and subsequent outcomes in patients assigned to finerenone or placebo.

Navigating Children's Risky Play: A Comparative Analysis of Saudi Mothers and Fathers.

Despite documented benefits for development, children are engaging in considerably fewer risky play activities. Research on parent gender and children's risky play is inconsistent. Gender and cultural context shape how individuals perceive and tolerate children's risky play.

The Impact of Contemporary Glucagon-like Peptide-1 Receptor Agonists on the Onset, Severity, and Conversion to Arthroplasty in Hip and Knee Osteoarthritis.

Background: The growing popularity of glucagon-like peptide-1 receptor agonists (GLP-1-RAs) for weight loss could significantly impact joint preservation and arthroplasty. While this will in part be driven by the association between obesity, osteoarthritis (OA), and total joint arthroplasty (TJA), recent evidence also indicates that GLP-1-RAs may have direct joint-protective, anti-inflammatory effects.

Purpose: To evaluate the association between GLP-1-RA use and the onset and progression of hip and knee OA in an obese population.

Targeting mitophagy in neurodegenerative diseases.

Mitochondrial dysfunction is a hallmark of idiopathic neurodegenerative diseases, including Parkinson disease, amyotrophic lateral sclerosis, Alzheimer disease and Huntington disease. Familial forms of Parkinson disease and amyotrophic lateral sclerosis are often characterized by mutations in genes associated with mitophagy deficits. Therefore, enhancing the mitophagy pathway may represent a novel therapeutic approach to targeting an underlying pathogenic cause of neurodegenerative diseases, with the potential to deliver neuroprotection and disease modification, which is an important unmet need.

Healthcare burden of narcolepsy in Japan: A retrospective analysis of health insurance claims from the Japan Medical Data Center.

Background: Narcolepsy is a chronic disorder that requires lifelong management; however, few studies have evaluated disease burden of narcolepsy. We estimated the healthcare burden of narcolepsy in Japan using data from the Japan Medical Data Center health insurance claims database.

Methods: This was a retrospective analysis of clinical burden, healthcare resource utilization, and costs among incident narcolepsy cases and matched controls identified between January 1, 2014 and December 31, 2019.

Prevention of liver cancer in the era of next-generation antivirals and obesity epidemic.

Preventive interventions are expected to substantially improve the prognosis of patients with primary liver cancer, predominantly hepatocellular carcinoma (HCC) and cholangiocarcinoma. HCC prevention is challenging in the face of the evolving etiological landscape, particularly the sharp increase in obesity-associated metabolic disorders, including metabolic dysfunction-associated steatotic liver disease (MASLD). Next-generation anti-HCV and HBV drugs have substantially reduced, but not eliminated, the risk of HCC and have given way to new challenges in identifying at-risk patients.

Buparlisib and Paclitaxel in Patients with Head and Neck Squamous Cell Carcinoma: Immunogenomic Biomarkers of Efficacy from the BERIL-1 Study.

Background: BERIL-1 was a randomized phase 2 study that studied paclitaxel with either buparlisib, a pan-class I PIK3 inhibitor, or placebo in patients with recurrent or metastatic (R/M) head and neck squamous cell cancer (HNSCC). Considering the therapeutic paradigm shift with immune checkpoint inhibitors (ICIs) now approved in the first-line setting, we present an updated immunogenomic analysis of patients enrolled in BERIL-1, including patients with immune-infiltrated tumors.

Objective: The objective of this study was to identify biomarkers predictive of treatment efficacy in the context of the post-ICI therapeutic landscape.

Prognostic significance of immune reconstitution following CD19 CAR T-cell therapy for relapsed/refractory B-cell lymphoma.

Immune deficits after CD19 chimeric antigen receptor (CAR) T-cell therapy can be long-lasting, predisposing patients to infections and non-relapse mortality. In B-cell non-Hodgkin lymphoma (B-NHL), the prognostic impact of immune reconstitution (IR) remains ill-defined, and detailed cross-product comparisons have not been performed to date. In this retrospective observational study, we longitudinally characterized lymphocyte subsets and immunoglobulin levels in 105 B-NHL patients to assess patterns of immune recovery arising after CD19 CAR-T.

Impact of alternative diagnostic labels for melanoma in situ on management choices and psychological outcomes: protocol for an online randomised study.

Introduction: A diagnosis of melanoma in situ presents negligible risk to a person's lifespan or physical well-being, but existing terminology makes it difficult for patients to distinguish these from higher risk invasive melanomas. This study aims to explore whether using an alternative label for melanoma in situ may influence patients' management choices and anxiety levels.

Methods And Analysis: This study is a between-subjects randomised online experiment, using hypothetical scenarios.

Ultrasensitive ctDNA detection for preoperative disease stratification in early-stage lung adenocarcinoma.

Circulating tumor DNA (ctDNA) detection can predict clinical risk in early-stage tumors. However, clinical applications are constrained by the sensitivity of clinically validated ctDNA detection approaches. NeXT Personal is a whole-genome-based, tumor-informed platform that has been analytically validated for ultrasensitive ctDNA detection at 1-3 ppm of ctDNA with 99.

Retinal vascular fingerprints predict incident stroke: findings from the UK Biobank cohort study.

Objective: To investigate the associations between a comprehensive set of retinal vascular parameters and incident stroke to unveil new associations and explore its predictive power for stroke risk.

Methods: Retinal vascular parameters were extracted from the UK Biobank fundus images using the Retina-based Microvascular Health Assessment System. We used Cox regression analysis, adjusted for traditional risk factors, to examine the associations, with false discovery rate adjustment for multiple comparisons.