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A study on infrared-visible fusion multimodal object detection algorithm based on cross-modal information bottleneck and minimum redundancy transformation

STELLAR: Phase III, Randomized, Open-Label Study of Eflornithine Plus Lomustine Versus Lomustine Alone in Patients With Recurrent Grade 3 Astrocytoma

PURPOSE STELLAR (ClinicalTrials.gov identifier: NCT02796261 ) was a phase III, randomized, open-label trial of eflornithine + lomustine versus lomustine monotherapy in patients with recurrent grade 3 astrocytoma. METHODS At trial initiation, eligibility criteria included: age ≥18 years, anaplastic astrocytoma (2016 WHO CNS Tumor classification [WHO CNS4]), first recurrence ≥6 months after radiation and temozolomide (TMZ), Karnofsky performance status ≥70, and no imaging findings consistent with grade 4 glioblastoma. Random assignment (1:1) was stratified by isocitrate dehydrogenase ( IDH ) mutation, age, resection extent, and geography. Patients received eflornithine (2.8 g/m 2 orally, every 8 hours [2 weeks on, 1 week off]) + lomustine (90 mg/m 2 orally, once every 6 weeks), or lomustine monotherapy (110 mg/m 2 once every 6 weeks). The primary end point was overall survival (OS). RESULTS Among 343 patients randomly assigned across 74 sites in eight countries, there was no difference in survival between eflornithine + lomustine and lomustine monotherapy (median OS 23.4 v 20.3 months, hazard ratio [HR], 0.94). Following changes in classification and grading in the 2021 WHO CNS5, a subset analysis of patients with IDH- mutant, grade 3 astrocytoma (n = 196), defined in 2024, before unblinding, showed clinically meaningful improvements in median OS with eflornithine + lomustine versus lomustine monotherapy (34.9 v 23.5 months, HR, 0.64) and median progression-free survival (PFS, 15.8 v 7.2 months, HR, 0.57). No differences were observed among patients with CNS grade 4 disease. Grade ≥3 treatment-emergent adverse events of relevance were related to reversible myelosuppression (eflornithine + lomustine 42% v lomustine monotherapy 29% of patients) and hearing impairment (24% v 0%). No new safety signals were identified. CONCLUSION Clinically meaningful improvements were observed; eflornithine + lomustine doubled PFS and improved OS in patients with recurrent IDH -mutant, grade 3 astrocytoma, but not grade 4 tumors, after prior radiotherapy and TMZ, consistent with its cytostatic mechanism of action.

Huntington’s disease LIG1 modifier variant increases ligase fidelity and suppresses somatic CAG repeat expansion

Huntington’s disease (HD) is a fatal neurodegenerative disorder caused by inheriting an expanded CAG repeat tract in the huntingtin gene ( HTT ) that further expands in somatic cells over an individual’s lifetime. Genome-wide association studies have provided critical insight into factors that modify the course of disease. These include DNA repair genes that alter the rate of somatic expansion and other genes that do not appear to directly influence this process. One modifier gene is DNA ligase 1 ( LIG1 ), in which a variant specifying a lysine to asparagine substitution (K845N) is associated with a profound (7 to 8 y) delay in the onset of motor signs. Here, we have taken a multifaceted approach to gain insight into the protective nature of this variant in HD. We demonstrate using in vitro ligase assays and enzyme kinetics that K845N enhances discrimination toward mismatched substrates and increases repair fidelity. Consistent with increased ligation fidelity, K845N confers protection against oxidative stress in cell-based assays. Finally, we demonstrate that the mouse LIG1 K843N orthologue suppresses somatic CAG expansion in HD knock-in mice. Overall, our data provide evidence that altered LIG1 function due to the K845N substitution may contribute to HD clinical delay by slowing somatic expansion in the brain and protecting the genome globally against damage. Significantly, our results provide a mechanistic foundation for considering DNA ligase fidelity as a therapeutic target in HD and potentially in other trinucleotide repeat disorders.

Baobab isotope records and rainfall forcing in Southwest Madagascar over the last 700 years

Highly resolved climate records for Madagascar are scarce but are essential for understanding of rainfall drivers over time and assessing the risks and likely trajectories of future climate change. We measured variation in the carbon isotopes of baobabs ( Adansonia spp.) which reflect rainfall in southwest Madagascar. The record indicates a decreasing trend of rainfall over the last 700 years with high variability at a centennial-scale. The duration of wetter periods decreased over time with the wettest periods between 1350–1450 CE, after the onset of the Little Ice Age, while the driest period occurred between 1600–1750 CE, during the Maunder Minimum. The results suggest that decadal to centennial rainfall variability in southwest Madagascar is dominated by tropical forcing rather than subtropical forcing. Wetter periods are regulated by the movement and migration of easterly winds linked to the Intertropical Convergence Zone, while dry periods are influenced by the effect of the Pacific Decadal Oscillation linked to the El Niño Southern Oscillation and the sea surface temperature variation in the Southwestern Indian Ocean. The Southern Annular Mode is significantly correlated with the record, but its effect was only visible at the beginning of the record around 1300 CE. This evidence provides a new understanding of rainfall across southern Africa and the interaction of global forcing with regional factors. Further investigation is required to improve tree chronology from Southern Hemisphere and understand the migration of the westerlies and its potential future effect on the rainfall in Madagascar. Understanding the interplay between tropical and other rainfall forcings will be essential in assessing likely scenarios of resilience, and adaptive capacity of social-ecological systems in Madagascar.

Comparison of explosively driven shock tube and open-air blast wave propagation

TBCRC 048 (Olaparib Expanded) Expansion Cohorts: Phase II Study of Olaparib Monotherapy for Patients With Metastatic Breast Cancer With Germline Mutations in <i>PALB2</i> or Somatic Mutations in <i>BRCA1</i> or <i>BRCA2</i>

PURPOSE Translational Breast Cancer Research Consortium 048 was a proof-of-principle trial demonstrating responses to the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib in patients (pts) with metastatic breast cancer (MBC) with germline (g) PALB2 or somatic (s) BRCA mutations (s BRCA m). Here we report results from the expansion cohorts in a larger sample of pts with g PALB2 m or s BRCA m. METHODS Eligible pts had MBC of any subtype with measurable disease and a g PALB2 m or s BRCA m. Pts received olaparib 300 mg twice a day until progression. The primary end point was overall response rate. Secondary end points include clinical benefit rate (CBR) at 18 weeks, progression-free survival (PFS), duration of response (DOR), and whether among s BRCA m carriers the mutant allele frequency (MAF) is significantly higher in responders than in nonresponders. RESULTS Fifty-four pts with g PALB2 m (N = 24) or s BRCA m (N = 30) were enrolled. Forty-two (78%) had estrogen receptor–positive human epidermal growth factor receptor 2–negative (HER2–) MBC, seven (13%) had triple-negative breast cancer, and five (9%) had HER2+ disease. Among pts with a g PALB2 m, the overall response rate (ORR) was 75% (80% CI, 60.2 to 86.3), CBR was 83.3% (90% CI, 65.8 to 94.1), the median PFS was 9.4 months (90% CI, 8.3 to 13.1), and the median DOR was 7.0 months (90% CI, 5.6 to 10.4). Among pts with s BRCA m (15 s BRCA1 and 15 s BRCA2 ), the ORR was 36.7% (80% CI, 24.7 to 50), CBR was 53.3% (90% CI, 37 to 69.1), the median PFS was 5.5 months (90% CI, 2.8 to 8.3), and the median DOR was 11.2 months (90% CI, 4.4 to not reached). One additional pt had an unconfirmed partial response. Although clinically meaningful, the ORR in pts with s BRCA m did not achieve the prespecified target. Among s BRCA m carriers, the mean MAF did not differ significantly between responders (46%) and nonresponders (39%; P = .7). CONCLUSION Olaparib is active in pts with MBC with g PALB2 m and s BRCA m, significantly expanding the population of pts with breast cancer likely to benefit from PARP inhibitors beyond g BRCA1/2 m carriers.

HES1 oscillations are required for cell cycle reentry in oestrogen receptor–positive breast cancer cells

Long-term recurrence in breast cancer is driven by reactivation of dormant disseminated tumor cells (DTCs) and remains a major clinical challenge, particularly in estrogen receptor–positive (ER + ) tumors. This process is underpinned by regulation of the cell cycle machinery that controls quiescence maintenance and exit. HES1, a Notch pathway transcription factor, regulates key cell cycle genes and has been shown to demonstrate protein expression oscillations. Here, we sought to establish whether HES1 oscillations may regulate ER+ cancer cell quiescence and reactivation. To investigate this, we developed a fundamental in vitro model of cell cycle arrest and reentry based on reversible CDK4/6 inhibition (CDK4/6i) with palbociclib, compatible with quantitative single-cell live-imaging of a knock-in endogenous HES1 reporter. Consistent with earlier findings, HES1 exhibited ~24 h protein oscillations in cycling cells demonstrating a reproducible dip in protein expression prior to S-Phase. During CDK4/6i-mediated arrest, the ~24 h HES1 oscillation was lost, HES1 levels were maintained at a moderately higher level and HES1 exhibited smaller dips. Similar changes were observed in unperturbed, spontaneously quiescent cells. Following release from CDK4/6i and cell cycle reentry, these alterations were reversed and the characteristic G1/S HES1 dip was observed. Preventing this dip at the point of release, by inducibly sustaining HES1 with a Tet-On system, upregulated the cell cycle inhibitor p21, impeded cell cycle reentry and induced cell death. These findings suggest that manipulating HES1 dynamics could represent a promising therapeutic approach to prevent reactivation of dormant tumor cells.

Minimum standards for physical therapists providing rehabilitation care for people with chronic respiratory diseases in Japan: An e-Delphi study

Addressing lightning and market uncertainties in self-scheduling: A fuzzy-markov approach for smart grids

Integrated Molecular Diagnosis Paving the Way for Therapeutic Success in Recurrent Astrocytoma Treatment

ADAR-GPT: Learning the language of the epitranscriptome

Symptom experiences of patients after cardiac valve surgery: A qualitative study

Introduction Heart valve disease is a leading cause of morbidity and mortality worldwide, with surgery being the gold standard treatment.Although clinical management focuses on postoperative functional recovery, the burden of symptoms is often inadequately characterized, despite its significant impact on healthcare resource utilization and health-related quality of life.Current evidence highlights notable gaps in understanding the subjective symptom experience after cardiac valve surgery, particularly regarding the long-term evolution of symptoms and their psychosocial impact. Objective This qualitative study aimed to systematically identify and characterize the most troubling symptom domains, specific symptoms, and symptom coping styles in patients after aortic or mitral valve replacement. Methods We conducted semi-structured interviews with 14 adult patients (ages 26-76 years) who underwent minimally invasive or sternotomy-based valve replacement surgery at a tertiary cardiovascular center in Nanjing, China. Results Fourteen patients (ages 26–76 years) participated in the study, from whose narratives three overarching themes and 14 subthemes were derived through thematic analysis.The analysis revealed the following:1) Physical Dimension of Symptom Experience, covering dynamic multisystem symptoms like respiratory discomfort, pharyngeal/oral issues, circulatory problems, digestive/excretory troubles, surgical pain, fatigue/weakness, and sleep disturbance; 2) Psychological Dimension of Symptom Experience, including intrinsic psychological adaptation (positive/negative) and emotional reactions to external factors (clinician interactions, family support, medical technology dependence); 3) Cognitive Dimension of Symptom Experience, involving transient ICU cognitive changes (disorientation, hallucinations) and symptom cognition (viewing pain/fatigue as inevitable, age-symptom speculation); 4) Symptom Experience and Coping Strategies in the Behavioral Dimension, encompassing passive symptom-induced behaviors and active coping (non-pharmacological, pharmacological, support-seeking). Conclusions This study shows cardiac valve surgery patients have multidimensional, dynamic postoperative experiences. They face diverse multisystem physical symptoms, mixed positive/negative psychological states, transient ICU-related cognitive changes, and both passive and active coping strategies (with individual differences). It highlights the need for holistic, individualized postoperative care to improve recovery and quality of life.

Knowledge, economic, and WASH challenges affecting menstrual health and hygiene among nursing students in Bangladesh using a mixed-methods approach

Erratum: Rise and Fall of Neoadjuvant Carboplatin for Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer

Phagocytes as plaque catalysts: Human macrophages generate seeding-competent Aβ42 fibrils with cross-seeding activity

The prevailing view frames microglia and macrophages as guardians against amyloid beta (Aβ) accumulation in Alzheimer’s disease (AD). Here, we overturn this paradigm by demonstrating that human phagocytic cells, including differentiated THP-1 macrophages and hESC-derived microglia, are not merely passive responders but active producers of extracellular, seeding-competent Aβ42 fibrils, the amyloid species most strongly linked to parenchymal plaque formation and neurodegeneration. These cell-generated aggregates differ structurally and functionally from synthetic fibrils, displaying enhanced seeding and tau cross-seeding activity in biosensor models. Notably, Aβ42 fibril formation in this system requires active cellular processes and is exacerbated by loss of Triggering Receptor Expressed on Myeloid Cells 2 (TREM2), a major AD risk gene. Transcriptomic profiling reveals an early inflammatory response resembling microglial states observed in human AD models. Together, these findings support emerging evidence from in vivo studies that macrophages and microglia can influence amyloid seeding and introduce a human-relevant in vitro platform to explore how Aβ aggregation intersects with innate immune function and genetic risk. Our results reinforce the concept that microglia may play a dual role in AD, acting both as responders and inadvertent facilitators of amyloid assembly, with implications for early therapeutic intervention.

Single-cell omics reveals arg-1 as a key regulator of age-dependent macrophage-mediated cartilage repair

Aging impairs cartilage repair, with young animals exhibiting superior regenerative capacity due to enhanced tissue repairing and reduced inflammation compared to aged counterparts. This study employed single-cell omics to dissect age-dependent immune cell heterogeneity in cartilage injury, revealing a critical deficiency in anti-inflammation macrophage subsets in aged animals. We identified Arg-1 as a central regulator of macrophage polarization, demonstrating that its overexpression rescues impaired repair in aged animals. These findings establish Arg-1 as a novel therapeutic target to counteract age-related declines in cartilage regeneration, offering new insights into macrophage-driven tissue repair mechanisms. The integration of single-cell analysis with functional validation provides a framework for developing precision interventions for age-impaired tissue regeneration.

The key m6A methylation regulator IGF2BP1 possesses potential prognostic value in papillary thyroid carcinoma

Enhancing Representation and Reporting of Body Mass Index in Cancer Randomized Clinical Trials

Allosteric gating of radical transport in ribonucleotide reductase

Association between family nurturing environment and screen exposure among preschool children aged 3–6 years in Shanghai: A cross-sectional study

Background Excessive or early screen exposure has been deemed associated with both immediate and long-term health impairment among preschool children. This study aimed to investigate the association between family nurturing environment and screen exposure among preschool children aged 3–6 years. Materials and methods A multi-stage stratified cluster sampling method was utilized to sample the kindergarten children aged 3-6 years from a district in Shanghai, China. From April to May 2023, parents completed an online questionnaire. Children's screen exposure was defined as more than 1 hour (hr) per day of screen-based devices use, and the daily screen time was categorized into three groups: non-exposure (&lt;1hr/ day), low exposure (1-4 hrs/ day), and high exposure (&gt;4 hrs/ day). Univariate and multivariate cumulative logit regression models were adopted to identify the determinants of screen exposure. Results A total of 1917 preschool children were included. Of these, 1604 (83.7%) were exposed to screens for more than 1 hr per day. High, low, and non-exposure groups comprised 313 (16.3%), 1291 (67.4%), and 313 (16.3%) children, respectively. The multivariate cumulative logit model showed that parental education, monthly household income, presence of screen-based devices in the bedroom, and parental screen use in front of children were positive determinants of more severe screen exposure for preschoolers. Conversely, older age, absence of siblings, co-viewing with the child, and parental restriction of screen time were negative determinants of more severe screen exposure. Conclusions Our findings suggest that interventions targeting parental behavior and cognitive practices may be more effective in promoting healthy screen exposure habits in preschool children.