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Error Function Regularization: A New Approach to Sparse Logistic Regression
Full text linkWe introduce the ERror Function (ERF) for sparse logistic regression. The ERF regularization interpolates between the L0 norm, which measures the number of non-zero elements in a vector, and its convex relaxation, the L1 norm, controlled by a hyper-parameter. Building on an Iterative Reweighted L1 (IRL1) scheme and the Alternating Direction Method of Multipliers (ADMM), we develop an effective algorithm to minimize the proposed model and analyze its convergence. Experiments on both synthetic and real high-dimensional datasets demonstrate the empirical competitiveness of our approach
Artificial Intelligence-Enhanced Molecular Profiling of JAK-STAT Pathway Alterations in FOLFOX-Treated Early-Onset Colorectal Cancer
Full text linkEarly-onset colorectal cancer (EOCRC) continues to rise, with the steepest increases observed among Hispanic/Latino (H/L) populations, underscoring the urgency of identifying ancestry- and treatment-specific biomarkers. The JAK-STAT signaling axis plays a central role in colorectal tumor biology, yet its relevance under FOLFOX-based chemotherapy in EOCRC remains poorly defined. In this study, we evaluated 2515 colorectal cancer (CRC) cases (266 H/L; 2249 non-Hispanic White [NHW]), stratifying analyses by ancestry, age of onset, and FOLFOX exposure. Statistical comparisons were performed using Fisher’s exact and chi-square tests, and survival patterns were assessed via Kaplan–Meier analysis. To extend conventional analytics, we deployed AI-HOPE and AI-HOPE-JAK-STAT, conversational artificial intelligence platforms capable of harmonizing genomic, clinical, demographic, and treatment variables through natural language queries, to accelerate multi-parameter biomarker exploration. JAK-STAT pathway alterations showed marked variation by ancestry and treatment context. Among H/L EOCRC cases, alterations were significantly enriched in patients who did not receive FOLFOX compared with those who did (21.2% vs. 4.1%; p = 0.003). A similar pattern emerged in late-onset CRC (LOCRC) NHW patients, where alterations were more frequent without FOLFOX exposure (13.3% vs. 7.5%; p = 0.0002). Notably, JAK-STAT alterations were significantly more common in untreated H/L EOCRC compared with untreated NHW EOCRC (21.2% vs. 9.9%; p = 0.002). Survival analyses revealed that JAK-STAT pathway alterations conferred improved overall survival across several NHW strata, including EOCRC treated with FOLFOX (p = 0.0008), EOCRC not treated with FOLFOX (p = 0.07), and LOCRC not treated with FOLFOX (p = 0.01). These findings suggest that JAK-STAT alterations may function as ancestry- and treatment-dependent prognostic markers in EOCRC, particularly among disproportionately affected H/L patients. However, prognostic interpretation in H/L subgroups is limited by small mutation-positive sample sizes, reflecting historical underrepresentation and highlighting the need for larger ancestry-balanced studies. The integration of AI-enabled platforms streamlined analyses and reveals the potential of artificial intelligence to accelerate discovery and advance precision medicine for populations historically underrepresented in cancer genomics research
End-of-Life and Palliative Care Disparities Among American Indians and Alaska Natives with Cancer: A Scoping Review.
Full text linkPurpose To identify disparities in access, utilization, and quality of end-of-life (EOL) and palliative care services for American Indians and Alaska Natives (AIAN) with cancer in the US. Methods Systematic searches were conducted in PubMed/MEDLINE, Embase, and Scopus. English-language original research studies reporting any quantitative estimates of measures of care quality or utilization for EOL and palliative care for AIAN individuals with cancer compared to other races were included (2014-2025). Screening and data extraction were conducted by two independent reviewers and discrepancies were resolved through consensus. Findings were synthesized through iterative team discussions. Results Of 1693 unique records, 153 underwent full-text review, and 22 met inclusion criteria. Considerable heterogeneities were observed in EOL care outcomes and covariates included in multivariable regression models assessing disparities: Compared to White individuals, AIAN individuals with cancer had significantly lower in-home or hospice and higher medical facility deaths (9/11 studies); higher acute care use (3/4 studies); lower hospice use (2/4 studies); lower anxiolytic medication use (1/1 study); and higher receipt of any palliative treatment (3/6 studies); but no differences in late hospice initiation (0/3 studies); or aggressive treatment near the EOL period (0/6 studies). Conclusions AIAN individuals with cancer appear more likely to experience a medicalized death. Mechanisms underlying these disparities remain poorly understood. Future studies should provide greater clarity in analytical methods to improve interpretability of disparities measures, use more consistent measures of EOL care quality, explore within-AIAN variation such as regional, tribal, and rural-urban differences, as well as cultural implications for the delivery of appropriate EOL care
Erratum to ‘Pooled analysis of trastuzumab deruxtecan retreatment after recovery from grade 1 interstitial lung disease/pneumonitis’ [Annals of Oncology. Volume 36, Issue 11, November 2025, Pages 1389-1399]
Full text linkErratum to "Pooled analysis of trastuzumab deruxtecan retreatment after recovery from grade 1 interstitial lung disease/pneumonitis
Meeting physical activity guidelines in conjunction with higher protein intake: associations with appendicular lean soft tissue index in middle aged adults with cancer
Full text linkBackground Loss of muscle mass is a common concern among patients with cancer. The aim of this study was to examine whether meeting the World Health Organization physical activity guidelines in combination with a higher vs. lower than the recommended daily allowance (RDA) protein intake is associated with greater appendicular lean soft tissue index (ALSTI) in adults aged 40–59 years with cancer from the National Health and Nutrition Examination Survey. Methods Participants were categorized by physical activity levels (moderate ≥ 150 min/week or vigorous ≥ 75 min/week) and protein intake (> 0.8 vs. ≤ 0.8 g/kg/day) assessed via two interviewer-administered 24-h dietary recalls. ALSTI was calculated using dual-energy X-ray absorptiometry (kg/m2). Linear regression models estimated associations, adjusting for demographic, clinical, and dietary covariates. Results Among 169 participants (mean age 51.0 ± 5.6 years; 69% women, mean ALSTI 7.74 ± 1.66 kg/m2), those meeting vigorous or moderate physical activity guidelines with higher protein intake did not show a significant association with ALSTI in the fully adjusted models (vigorous: β = 0.08, standard error (SE) 0.12, p = 0.53; moderate: β = -0.05, SE 0.15, p = 0.76). However, a significantly positive link was found in those meeting both vigorous and moderate physical activity (β = 0.40, b SE 0.02, p < 0.01). Conclusions Meeting vigorous or moderate physical activity guidelines in combination with higher vs. lower protein intake was not associated with ALSTI in adults with cancer. However, meeting both was positively linked to ALSTI. Longitudinal and interventional studies using objective measures and longitudinal designs are needed to clarify the role of physical activity with adequate protein intake in preserving muscle health in this clinical population
Effects of lifestyle interventions in pregnancy on gestational diabetes: individual participant data and network meta-analysis
Full text linkOBJECTIVES: To assess the effects of lifestyle interventions on gestational diabetes, determine whether the effects vary by maternal body mass index, age, parity, ethnicity, education level, or intervention, and rank interventions by effectiveness. DESIGN: Individual participant data (IPD) and network meta-analysis. DATA SOURCES: Major electronic databases (January 1990 to April 2025). METHODS: This meta-analysis included randomised trials on the effects of lifestyle interventions (physical activity based, diet based, or mixed) in pregnancy on gestational diabetes. Main outcomes were gestational diabetes defined by any criteria and by UK NICE (National Institute for Health and Care Excellence) criteria; other outcomes included IADPSG (International Association of Diabetes in Pregnancy Study Group) and modified IADPSG defined gestational diabetes. A two stage IPD meta-analysis estimated summary odds ratios and 95% confidence intervals and interactions (subgroup effects), along with absolute risk reduction estimates. Aggregate data from non-IPD trials were added to the meta-analysis when possible. Intervention effects were ranked using network meta-analysis. RESULTS: 104 randomised trials (35 993 women) were included, with IPD for 68% of participants (24 391 women; 54 studies). Lifestyle interventions reduced gestational diabetes defined by any criteria by 10% in IPD trials (odds ratio 0.90, 95% confidence interval (CI) 0.80 to 1.02; absolute risk reduction 1.3%, 95% CI -0.3% to 2.6%), and by 20% when combining IPD and non-IPD trials (odds ratio 0.80, 95% CI 0.73 to 0.88; absolute risk reduction 2.6%, 95% CI 1.6% to 3.6%), and no reduction was observed using NICE criteria (odds ratio 0.98, 95% CI 0.84to 1.13). Lifestyle interventions reduced gestational diabetes defined using IADPSG criteria by 14% in IPD trials (odds ratio 0.86, 95% CI 0.75 to 0.97; absolute risk reduction 2.7%, 95% CI 0.6% to 5.0%) and by 18% when combining IPD and non-IPD trials (odds ratio 0.82, 95% CI 0.72 to 0.93; absolute risk reduction 3.5%, 95% CI 1.3% to 5.7%). Effects did not vary by maternal characteristics, except for education. Although women of all educational levels benefited from the intervention, the benefit was less in those with low education (low v middle interaction: odds ratio 0.68, 95% CI 0.51 to 0.90; low v high interaction: odds ratio 0.71, 95% CI 0.54 to 0.93). Benefits did not vary by intervention characteristics, except for greater effectiveness with group format (odds ratio 0.81, 95% CI 0.68 to 0.97; absolute risk reduction 2.5%, 95% CI 0.4% to 4.3%) and newly trained facilitators (odds ratio 0.82, 95% CI 0.69 to 0.96; absolute risk reduction 2.4%, 95% CI 0.5% to 4.2%). Physical activity based interventions ranked highest (mean rank 1.1, 95% CI 1 to 2) in preventing gestational diabetes. CONCLUSIONS: Lifestyle interventions in pregnancy are likely to prevent gestational diabetes, with effects varying according to diagnostic criteria. Implementation strategies should address inequalities by maternal education, and consider group formats, provider training, and physical activity based interventions to prevent gestational diabetes. STUDY REGISTRATION: PROSPERO CRD42020212884
Genomic adaptation strategies to habitat switching in Korarchaeota
Full text linkKorarchaeota, an ancient lineage of archaea, has long been overlooked in discussions of archaeal and eukaryotic evolution. Their physiology and evolutionary history have remained enigmatic due to their rarity in natural environments. Here, we assembled 101 Korarchaeota genomes from different seafloor hydrothermal vents and terrestrial hot springs, revealing that Korarchaeota lineages have undergone multiple transitions between marine and terrestrial habitats. These transitions were accompanied by genomic shifts reflecting adaptations to habitat-specific physicochemical conditions, including variations in nutrient availability, potential energy sources, osmotic conditions, and viral predation stresses. Molecular dating suggests that Korarchaeota originated ~2.84 billion years (Ga) ago, with three subsequent diversification events occurring around 2.42, 1.52, and 1.29 Ga ago. These major diversifications coincide with key geological events such as the Great Oxidation Event and the breakup and formation of supercontinents. Our findings provide insights into the evolutionary trajectory and ecological adaptations of Korarchaeota, thereby enhancing our understanding of microbial coevolution with Earth’s dynamic surface environments.The adaptation of Korarchaeota across changing habitats tracks their coevolution with Earth throughout its dynamic history
Renal Function
Full text linkThis document summarizes the rationale, equipment, protocol, assay, internal quality control, data cleaning, external quality control, and procedures for the measurement and classification of kidney (renal) function at the Wave VI home exam. Whenever possible, data collection and methods in Wave VI mirrored those of Wave V to ensure comparability of data between waves, although important inter-Wave differences exist and are grey-highlighted herein. This document is one in a set of Wave VI user guides.
Increasing dependability of caregiver implementation fidelity estimates in early intervention: A generalizability and decision study.
Full text linkThere is an increasing need to measure caregiver implementation of strategies from Naturalistic Developmental Behavioral Interventions (NDBIs) as a possible key mediator of outcomes in a child. The NDBI Fidelity (NDBI-Fi) rating scheme is a macro-code to estimate the implementation of core strategies. Yet, there is a need to understand the dependability of this measure to ensure intervention study findings are generalizable to everyday interactions and comparable across studies. We addressed this by evaluating the dependability or consistency of NDBI-Fi scores for 20 caregivers, averaged across observations of two occasions of two routines that were each scored by two raters. Our findings indicated that a single score (i.e. from a single occasion, single routine, and single rater) from the measure has low dependability (g = 0.43). When scores were averaged across two observations each of two routines scored by two raters (i.e. eight scores total), the score was more dependable (g = 0.77). The majority (81.6%) of absolute error variance was attributable to occasions of observation and its interaction with other facets (routine or rater). Therefore, we recommend the NDBI-Fi be applied to more than one observation of more than one routine to strengthen confidence that scores are generalizable to everyday parent-child interactions.Lay abstractOutcomes from caregiver-mediated interventions typically include measuring the caregiver's use of key techniques. The Naturalistic Developmental Behavioral Intervention-Fidelity (NDBI-Fi) tool is a valid measurement strategy for estimating caregiver use. In this study, we sought to understand how to improve data collection from natural observations of caregivers with their children to ensure the scores are representative of how the caregiver and child typically interact. We observed 20 caregiver-child pairs via telehealth in snack and play routines over two different days. Each video was rated using the NDBI-Fi by two observers. We learned that increasing the number of observations may be the best way to improve the dependability of scores from natural caregiver-child observations. This study adds to recent research seeking to understand how to best measure caregiver strategy use. These findings may guide future researchers and clinicians to consider increasing the number of observations used to evaluate caregiver use of intervention techniques in research studies or clinical practice
Pax Americana
Full text linkThis paper explores the trajectory of human history through the lens of conflict, positing that war—defined by the conquest of territory, the accretion of power, and the imposition of control—remains the fundamental organizing principle of civilization. It argues that while the mechanisms of hegemony have evolved from the kinetic seizure of land to the weaponization of capital and economic interdependence, the underlying drive for dominance remains constant. We analyze the current "Pax Americana" not merely as a post-1945 phenomenon, but as the mature phase of an imperial project rooted in the 19th-century industrialization and expansion of the United States. Despite a perceived domestic stagnation and political polarization, the United States has engineered a profound economic divergence from its global competitors, driven by a monopolistic eruption in Artificial Intelligence technologies. This paper presents a literature review of the "frozen" nature of modern conflict—exemplified by the Russo-Ukrainian War and the fractured stasis of the Middle East—arguing that the American stronghold on the global financial architecture actively suppresses the transition of power and the redrawing of borders. Finally, utilizing demographic projections and a thought experiment based on the Strauss-Howe generational theory and historical imperial lifespans, we posit that the United States is approaching a critical cyclical juncture, occupying a temporary and fragile position of supremacy that belies the historical inevitability of hegemonic transition