HCL Technologies (India)

Hormone receptor-positive (HR+) and HER2-negative (HER2−) early breast cancer (EBC) accounts for more than 70% of breast cancer diagnoses. Prognostic assessment is traditionally based on clinical and histological criteria, including tumor size, nodal involvement, histologic grade, and measures of tumor proliferation. Multigene expression assays and composite clinicopathological models further refine risk stratification in selected patients, particularly in those with intermediate-risk features, guiding adjuvant therapeutic choices. Adjuvant endocrine therapy (ET), typically with aromatase inhibitors in postmenopausal women or with ovarian suppression combined with either an aromatase inhibitor or tamoxifen in high-risk premenopausal patients, substantially reduces recurrence risk. Nevertheless, 15–30% of patients ultimately relapse, highlighting the need for improved risk stratification and treatment optimization. While extended ET beyond 5 years provides modest additional benefit in selected patients, this strategy must be carefully weighed against toxicity and quality-of-life considerations. The integration of targeted agents, including CDK4/6 inhibitors, into adjuvant ET expands therapeutic options for high-risk HR+/HER2− EBC, illustrating the ongoing treatment personalization. Emerging endocrine agents, such as oral selective estrogen receptor degraders (SERDs) and other next-generation estrogen receptor–targeted agents, aim to overcome endocrine resistance while improving tolerability and long-term adherence. In parallel, adaptive strategies integrating dynamic biomarkers, including genomic profiling and circulating tumor DNA (ctDNA) monitoring, are under active investigation to refine risk stratification and guide response-adapted interventions. Collectively, these advances support a biologically guided, response-adapted approach to optimize long-term outcomes while minimizing overtreatment, reflecting the ongoing shift toward precision oncology in HR+/HER2− EBC.

The DynamX bioadaptor, a novel coronary implant, is designed to restore vessel function when the thin polymer coating covering the helical strands resorbs 6 months post-percutaneous coronary intervention. We aimed to evaluate vessel conformability 1 year after percutaneous coronary intervention with the bioadaptor, compared with conventional drug-eluting stents (DESs). Vessel segments were 1:1 randomized to a novolimus-eluting bioadaptor or a durable polymer novolimus-eluting second-generation DES. Coronary computed tomography angiography was performed at 1 and 12 months post-implantation, and the 3-dimensional geometry of the treated segments in coronary computed tomography angiography was analyzed. The primary outcome was the change in dynamic vessel geometry, including curvature flexibility (bending motion), torsion flexibility (twisting motion), and path flexibility (3-dimensional motion) of the treated segment during the cardiac cycle. A total of 48 vessel segments in 48 patients were randomized, with 24 receiving bioadaptor and 24 receiving DES. In within-group paired analyses, the bioadaptor group showed a significant improvement in torsion flexibility from 1 to 12 months, whereas no significant change was observed in the DES group. Although curvature and path flexibility increased numerically in the bioadaptor group, these within-group differences were not statistically significant. However, when comparing the magnitude of change between groups, the increase in path flexibility was significantly greater with the bioadaptor than with DES, indicating a superior restoration of 3-dimensional vessel motion. The novel bioadaptor technology demonstrated favorable restoration of 3-dimensional dynamic geometry of the treated vessel segment 12 months after implantation, in comparison with traditional DES. These initial mechanistic findings suggest a potential explanation for the favorable clinical outcomes observed in prior trials, and our analytical approach may offer new insights to guide future vascular implant designs and evaluations. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04936191.

Street-level imagery plays a pivotal role in the development and maintenance of digital maps. This study introduces a novel approach for detecting road barriers using dashcam footage by explicitly integrating spatial domain knowledge into the learning process-a key advancement over existing self-supervised learning (SSL) methods that typically lack such spatial contextualization. Traditional supervised learning methods often struggle with generalizability across diverse data sources, especially when annotated datasets are limited. While current SSL approaches aim to overcome annotation scarcity, they generally focus on tasks unrelated to the target domain, resulting in learned features that do not effectively transfer or generalize. Our methodology addresses these limitations through a three-stage process-data curation, pretext model training, and fine-tuningthat leverages spatially related features from more accessible data. By employing foundational models to generate pseudo labels and training on this enriched data, the approach enhances feature relevance within the spatial domain. The final fine-tuning stage adapts the pretrained model for specific applications using minimal annotated data, thereby improving downstream task performance in data-scarce environments. This adaptable framework offers significant potential for various fields where spatial domain integration and limited annotation pose challenges.

Genome-wide association studies (GWAS) have identified germline genetic variants for follicular lymphoma (FL) susceptibility. We conducted a GWAS of prognosis in FL patients to identify genetic predictors of event-free survival (EFS) as well as failure within the first 24 months after treatment initiation (EFS24) using patients treated with rituximab-based immunochemotherapy from three clinical trials and one prospective observational study (N = 1054). Statistical approaches consisted of a pooled GWAS of the four cohorts and a leave-one-cohort-out (LOCO) strategy to identify robust findings that replicated across the four cohorts. The top SNPs for EFS and EFS24 were marked by rs72625024 at 3q27.3 near FETUB and HRG (P = 9.37 × 10-8) and rs114695031 at 14q32.13 near TCL6 (P = 1.93 × 10-8), respectively. These two loci, which were discovered and validated in all 4 LOCO rounds, map near long-non-coding RNAs with putative tumor suppressor functions. Our results pinpoint potential novel biology and the contribution of host genetics to prognosis in FL.

Abstract Background osteoarthritis (OA) is a prevalent chronic joint disorder, primarily affecting older adults, with higher frequency in females. It involves progressive cartilage degeneration, leading to pain and disability. The global prevalence of OA continues to rise, especially in aging populations, with the knee being the most affected site. OA is a multifactorial disease associated with obesity, mechanical stress, and systemic inflammation. No disease-modifying OA drugs are currently approved, and treatment is mostly symptomatic. This study aimed to provide updated epidemiological data and insight into clinical characteristics and treatment patterns of OA in Italy, through the implementation of a national rheumatology registry. Methods the ESORT registry, coordinated by the Italian Society of Rheumatology (SIR), included eight rheumatologic centers across Italy. Patients with clinical and radiographic OA at different joint sites were enrolled between 2016 and 2022. Data collected included demographics, BMI, affected joints, baseline VAS pain scores, and current or initiated treatments. Descriptive statistical analyses were performed on the pooled dataset. Results a total of 322 patients were included. The cohort had a female-to-male ratio of 2:1, with a mean age of 73.3 ± 14.7 years and mean BMI of 26.2 ± 4.5 kg/m². The most affected site was the knee (62%), followed by hip (40%), spine (38.2%), and hand (35%). Mean baseline VAS was 49.3 ± 22.2. Regarding treatment, 39.1% used non-selective NSAIDs, 28.8% paracetamol, 45% received hyaluronic acid injections, and 15.2% corticosteroid injections. Conclusions the ESORT registry offers critical insights into OA epidemiology in Italy, underscoring the need for further phenotype-driven research, and integrated care.

This action research aimed to identify and explore the instructional difficulties encountered by teachers in teaching the Filipino subject in rural elementary schools, as well as the interventions needed to address these challenges. The study employed a qualitative approach, gathering data from ten Filipino teachers through structured questionnaires. Findings revealed that teachers face multiple challenges, including insufficient Filipino books and instructional materials, students’ limited understanding of Filipino (language barriers), minimal daily use of the language, diverse learner abilities, and poor or unstable internet connectivity. To overcome these difficulties, teachers emphasized the importance of trainings and seminars, contextualized lessons, parental involvement and home follow-up, ICT and multimedia integration, collaborative learning activities, and organizing language-related school events. The study highlights the need for a holistic approach that combines resource provision, professional development, and community engagement to improve Filipino instruction in rural contexts. The findings underscore that, despite resource limitations, learner-centered strategies and innovative teaching practices can enhance student engagement, language proficiency, and motivation, ultimately contributing to a more effective and meaningful learning environment for Filipino learners.

Abstract Introduction Intracranial pressure (ICP) monitoring is commonly used in neuro-intensive care, but its utility may be limited by a suboptimal use. The brain pressure-volume relationship, a potential predictor of neurological health, is now approached using time-domain methods, which can be challenging to implement. Frequency-domain methods may offer an alternative, but their relationship with time-domain metrics remains unclear. This study compares time- and frequency-domain methods for assessing brain compliance and evaluates their real-time usability. Methodology A monocentric, prospective observational study was conducted in the neurological ICU of the Hospices Civils de Lyon, France, to evaluate markers of brain compliance. Adult patients with brain lesions requiring multimodal monitoring were included. Continuous high-density physiological data, including ICP, arterial blood pressure (ABP), end-tidal CO₂, and electrocardiogram (ECG), were collected for analysis. Some spontaneous ICP rise events were automatically detected based on heuristic criteria and used as brain compliance challenges to compare the co-evolution of metrics across multiple time windows. Time-domain (pulse shape-related metrics) and frequency-domain analyses (examining heart and respiratory components in ICP) were computed to assess the intracranial pressure-volume state. Statistical analyses were performed using linear mixed-effects modeling, adjusting for vasoactive and sedative medications and Spearman correlations. Results The study included 66 patients, with a mean age of 49.16 [38.38, 57.58] years. A total of 518 spontaneous ICP rise events were detected in 56 patients. Our findings revealed that: 1) frequency-domain metrics strongly correlated with time-domain metrics during these challenges (r > 0.8, p < 0.001), 2) frequency-domain metrics were significantly drastically less computationally demanding, and 3) the impact of the heart on ICP showed a significant correlation with the P2/P1 ratio (r = 0.391, p < 0.001) and other potential markers of brain compliance. In contrast, the impact of respiration on ICP was only marginally correlated with these markers. Conclusions Frequency-domain analyses exploring the impact of cardiac activity on ICP map provide similarly informative value to more complex machine learning-based tools, but with the advantage of being much less computationally demanding. This makes this approach particularly suitable and intuitive for real-time clinical monitoring in hospital settings, where computational resources are often limited. Authors statement Initials: VG, NE, GP, LB, FG, RC, CB, FC, AM, AR, RM, FD, TR, SG, BB Conception and Design: VG, NE, BB Data Collection : VG, NE, LB, GP, TR, FG, RC, CB, FC, FD, BB Data Analysis and Interpretation: VG, BB Methodology Development: VG, BB, SG Manuscript Drafting and Writing: VG, BB Supervision and Project Oversight: BB Funding Acquisition: BB, VG Visualization: VG, BB Critical Review and Editing: NE, GP, LB, FG, RC, CB, FC, AM, AR, RM, FD, TR, SG, BB Approval of the Final Version: All Software Development: VG, SG Ethical Approval and Regulatory Compliance: BB

Background:Patients with epithelial ovarian cancer (EOC) receiving neoadjuvant platinum-based chemotherapy (NACT) who remain ineligible for complete interval cytoreductive surgery (ICS) due to poor chemosensitivity (CA-125 KELIM™ score <1.0) have a poor prognosis (~20% 5-year survival). A weekly dose-dense carboplatin–paclitaxel regimen may improve outcomes in this high-risk subgroup.Objectives:To demonstrate the superiority of a salvage weekly dose-dense carboplatin–paclitaxel regimen over continuation of the standard 3-weekly regimen in poor-prognosis EOC patients after 3–4 cycles of standard NACT.Design:SALVOVAR is a pragmatic, open-label, multicenter, international, randomized phase III trial.Methods and analysis:Patients with stages III–IV high-grade EOC are eligible if they present (1) an unfavorable standardized KELIM score <1.0, and (2) a disease not amenable to complete ICS after 3–4 cycles of standard 3-weekly carboplatin–paclitaxel. Patients are randomized (1:1) to either the experimental arm (dose-dense carboplatin AUC5 day 1 plus paclitaxel 80 mg/m2 on days 1, 8, and 15, every 3 weeks) or the control arm (continuation of the standard regimen) for 3 cycles. Bevacizumab use is allowed at investigator discretion. Stratification factors include planned bevacizumab administration, BRCA mutation status, and KELIM strata. The two co-primary endpoints are (1) improvement in late complete cytoreduction rates (from 5% in the control arm to 20% in the experimental arm), and (2) overall survival (target hazard-ratio, 0.61). Total 250 patients will be randomized. Secondary endpoints include objective response rate, progression-free survival, and safety. Additional planned analyses include quality-of-life, cost-effectiveness, surgical standardization, human sciences, and biology studies.Ethics:The protocol was approved by the national ethics committee and health authorities.Discussion:SALVOVAR will evaluate whether chemotherapy densification improves outcomes in poorly chemosensitive advanced EOC. If positive, this pragmatic strategy could be implemented in large-scale studies, independent of resource setting.Trial registration:ClinicalTrials.gov NCT06476184 (June-2024). Available at: https://clinicaltrials.gov/study/NCT06476184