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Nevin Manimala Statistics

LLOT: application of Laplacian Linear Optimal Transport in spatial transcriptome reconstruction

Biometrics. 2026 Jan 6;82(1):ujag046. doi: 10.1093/biomtc/ujag046.

ABSTRACT

Single-cell RNA sequencing (scRNA-seq) allows transcriptional profiling, and cell-type annotation of individual cells. However, sample preparation in typical scRNA-seq experiments often homogenizes the samples, thus spatial locations of individual cells are often lost. Although spatial transcriptomic techniques, such as in situ hybridization (ISH) or Slide-seq, can be used to measure gene expression in specific locations in samples, it remains a challenge to measure or infer expression level for every gene at a single-cell resolution in every location in tissues. Existing computational methods show promise in reconstructing these missing data by integrating scRNA-seq data with spatial expression data such as those obtained from spatial transcriptomics. Here we describe Laplacian Linear Optimal Transport (LLOT), an interpretable method to integrate single-cell and spatial transcriptomics data to reconstruct missing information at a whole-genome and single-cell resolution. LLOT iteratively corrects platform effects and employs Laplacian Optimal Transport to decompose each spot in spatial transcriptomics data into a spatially-smooth probabilistic mixture of single cells. We benchmark LLOT against several existing methods on multiple datasets from different measurement technologies, including in situ hybridization, Slide-seq, 10x Visium, and Visium HD. The results demonstrate that LLOT provides an interpretable and versatile framework for reconstructing spatial gene expression and inferring cell locations.

PMID:41885893 | DOI:10.1093/biomtc/ujag046

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Nevin Manimala Statistics

Diagnosis and conceptualization of suicide: Why suicide belongs in dimensional frameworks of psychopathology

J Psychopathol Clin Sci. 2026 Mar 26. doi: 10.1037/abn0001126. Online ahead of print.

ABSTRACT

This article discusses the diagnosis and conceptualization of suicide. Addressing suicide and related phenomena is a top priority in mental health care but is not adequately reflected in the current categorical diagnostic system, the Diagnostic and Statistical Manual of Mental Disorders (DSM), Fifth Edition, Text Revision. Suicide demonstrates the pitfalls of categorical conceptualization of psychopathology and should be thoroughly examined within dimensional frameworks. This is particularly relevant as development of the newest iteration of the DSM-and renewed discussion of diagnosis and conceptualization of psychopathology-begins. The categorical nature of diagnosis has been critiqued at length, with the proposed alternative positing transdiagnostic dimensions that account for overlaps across and variations within diagnoses. Suicide and related phenomena do not appear as a distinct psychopathology/diagnosis in the DSM, Fifth Edition, Text Revision, instead comprising a symptom/criterion for only two of the almost 300 disorders. A transdiagnostic conceptualization of suicide aligns with historical and modern theories of suicide, none of which focus on psychiatric diagnoses as primary explanatory factors in suicide, and most of which emphasize transdiagnostic patterns of distress and biopsychosocial processes that better explain suicidal behavior. Discussion to date about limitations of the current diagnostic system regarding suicide has focused on adding suicide-related diagnoses or even positing an additional suicide-related axis when the DSM previously used an axial structure. Based on the characteristics of suicide and related phenomena described previously, the author hypothesizes that suicide-related processes comprise higher level dimensions-including a range of nonpathological (e.g., developmental changes in acceptance of death) to pathological phenomena and factors aligned with suicide theory (e.g., capability)-that interact with cross-cutting psychopathological and biopsychosocial factors to lead to varying phenotypes. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

PMID:41885890 | DOI:10.1037/abn0001126

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Nevin Manimala Statistics

A theory-driven structural equation modeling approach to the behavioral inhibition and behavioral activation systems model of chronic pain: Evaluating the mediating role of self-regulatory and volitional abilities

Health Psychol. 2026 Mar 26. doi: 10.1037/hea0001605. Online ahead of print.

ABSTRACT

Objective: Gray’s reinforcement sensitivity, describing elementary motivational systems that mediate cognitive-affective and behavioral responses to punishing (behavioral inhibition system [BIS]) and Rewarding (behavioral activation system [BAS]) stimuli, has been most widely applied in the study of the motivational underpinnings of pain-related responses. Empirical findings regarding the associations of BIS and BAS with pain-relevant clinical outcomes are inconsistent, however. Drawing on personality systems interaction theory, the present cross-sectional study aimed at evaluating the mediating role of self-regulatory and volitional abilities in the relationship between BIS and BAS-Reward sensitivity and pain-related activity patterns. Method: Our data analyses were based on 579 patients (74.8% women) with musculoskeletal pain who filled in self-report questionnaires operationalizing the constructs of interest. The projected relations among three levels of observed variables (level of temperament, self-regulation as mediating level, and behavioral dimensions as outcome level) were statistically tested by mediation analysis based on structural equation modeling. Results: Consistent with our predictions, we found the facilitating effects of BIS sensitivity on activity avoidance, and maladaptive dimensions of persistence and pacing behavioral dimensions to be mediated by self-regulation and volitional facilitation. Full mediation was also observed for the negative associations of BAS-Reward with pain avoidance, activity avoidance, and excessive persistence. Conclusions: Our study complements previous work by emphasizing the importance of emotional self-regulation and volition in behavioral responses to pain. New perspectives on the role of BAS-Reward in chronic pain are opened up. Our findings indicate that multimodal interventions fostering emotional self-regulation should be increasingly incorporated into existing pain management programs. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

PMID:41885889 | DOI:10.1037/hea0001605

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Implementing Practices for Full Therapy Participation for Patients With Candida auris in an Inpatient Rehabilitation Setting

Rehabil Nurs. 2026 Mar 26. doi: 10.1097/RNJ.0000000000000537. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the effectiveness of a dedicated rehabilitation gym space for patients with Candida auris (C. auris) requiring contact isolation in an inpatient rehabilitation setting. This initiative had an aim of improving access to the therapy gym while maintaining infection prevention protocols for patients with C. auris.

METHODS: Through collaboration with hospital leadership and public health authorities, a secondary gym space was identified and converted exclusively for patients with C. auris. Data collected over 14 months included patients’ functional outcomes and infection transmission rates.

RESULTS: Twenty-five patients with C. auris were admitted to the rehabilitation facility between December 2022 and March 2024; 18 received in-room therapy, and seven received therapy in the dedicated gym. A greater proportion of patients using the dedicated gym achieved mobility improvement goals (57.1%) compared with those who received therapy in-room (35.7%). Self-care and mobility score improvement scores for the two groups were not statistically significant. There were no instances of in-facility transmission of C. auris.

CONCLUSIONS: Rehabilitation health care workers can safely support functional progress in contact-isolated patients by using dedicated therapy spaces, maintaining infection control, and optimizing patients’ functional outcomes. Although we had a small sample , findings suggest that mobility outcomes may improve when C. auris patients have access to a dedicated gym. Further monitoring is needed to assess long-term impact.

PMID:41885879 | DOI:10.1097/RNJ.0000000000000537

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Nevin Manimala Statistics

Weight Changes With Tirzepatide and Concomitant Weight-Inducing Medications: Post Hoc Analysis of Randomized Clinical Trials

JAMA Netw Open. 2026 Mar 2;9(3):e263274. doi: 10.1001/jamanetworkopen.2026.3274.

ABSTRACT

IMPORTANCE: Given the common use of weight-inducing (WI) medications, it is crucial to understand the potential association of these medications with the effectiveness of obesity treatments.

OBJECTIVE: To assess the association between tirzepatide and weight reduction among participants with overweight or obesity who initiated WI medications during the SURMOUNT-1, -3, and -4 trials.

DESIGN, SETTING, AND PARTICIPANTS: This post hoc analysis of the phase 3 randomized clinical trials SURMOUNT-1 (December 4, 2019, to April 1, 2022), SURMOUNT-3 (March 29, 2021, to May 12, 2023), and SURMOUNT-4 (March 29, 2021, to May 18, 2023) assessed the association between tirzepatide and weight reduction among participants taking concomitant WI medications. Randomized participants (lead-in and randomized treatment period data) who started taking 1 or more WI medications for 3 or more months (≥1 week for oral corticosteroids) during the trial were included in the analysis. Statistical analysis was performed from July to December 2025 in the modified intent-to-treat population.

MAIN OUTCOMES AND MEASURES: WI medication use was summarized for all treatment arms from weeks 0 to 72 (SURMOUNT-1 and SURMOUNT-3) or weeks 0 to 88 (SURMOUNT-4). A mixed model of repeated measures was used to assess percentage change in weight from week 0 to week 72 or week 88 in the efficacy analysis sets (excluding off-treatment data), with 1 or more postbaseline weight measures.

RESULTS: This post hoc analysis comprised the WI medication subgroups of SURMOUNT-1 participants (N = 442; mean [SD] age, 48.0 [12.5] years; 325 women [73.5%]; mean [SD] body weight, 105.9 [22.4] kg), SURMOUNT-3 participants (N = 100; mean [SD] age, 49.5 [12.0] years; 75 women [75.0%]; mean [SD] body weight, 102.7 [23.5] kg), and SURMOUNT-4 participants (N = 134; mean [SD] age, 51.8 [11.9] years; 91 women [67.9%]; mean [SD] body weight, 111.8 [23.7] kg). Approximately one-fifth of participants used 1 or more WI medications (SURMOUNT-1, 17.4% [442 of 2539]; SURMOUNT-3, 17.3% [100 of 579]; and SURMOUNT-4, 20.0% [134 of 670]). Among them, 72.9% in SURMOUNT-1 (322 of 442), 68.0% in SURMOUNT-3 (68 of 100), and 64.9% in SURMOUNT-4 (87 of 134) were taking 1 nonsteroid WI medication, with 2.0% in SURMOUNT-1 (9 of 442), 3.0% in SURMOUNT-3 (3 of 100), and 2.2% in SURMOUNT-4 (3 of 134) using 3 or more medications. The mean (SD) duration of treatment with nonsteroid WI medications was 50.9 (28.8) weeks in SURMOUNT-1, 50.9 (29.3) weeks in SURMOUNT-3, and 58.1 (34.9) weeks in SURMOUNT-4. The mean percentage weight change compared with placebo from randomization to 72 weeks for those treated with tirzepatide and using WI medication was -13.3% (95% CI, -16.0% to -10.7%) for 5 mg to -21.3% (95% CI, -23.9% to -18.7%) for 15 mg in SURMOUNT-1 and -26.1% (95% CI, -30.0% to -22.3%) for the maximum tolerated dose in SURMOUNT-3, and from randomization to 88 weeks, it was -18.6% (95% CI, -20.9% to -16.3%) for the maximum tolerated dose in SURMOUNT-4.

CONCLUSIONS AND RELEVANCE: In this post hoc analysis of 3 randomized clinical trials for participants taking at least 1 concomitant WI medication, tirzepatide treatment was associated with weight loss comparable with the primary study results. These findings suggest that people with overweight or obesity who require treatment with WI medications may be able to achieve clinically meaningful weight reduction with tirzepatide.

TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT04184622, NCT04657016, NCT04660643.

PMID:41885866 | DOI:10.1001/jamanetworkopen.2026.3274

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Nevin Manimala Statistics

Intoxication in Children From Opioids Prescribed to Family Members

JAMA Netw Open. 2026 Mar 2;9(3):e263515. doi: 10.1001/jamanetworkopen.2026.3515.

ABSTRACT

IMPORTANCE: Worldwide, 480 000 deaths are attributable to opioids annually. The risk that they pose to children through family members’ prescriptions is unknown.

OBJECTIVE: To quantify the association between opioid prescriptions dispensed to a household family member and a serious opioid intoxication event (SOE) in a child.

DESIGN, SETTING, AND PARTICIPANTS: This case-control, population-based study used data from Denmark’s comprehensive nationwide longitudinal prescription and health care registries over a 27-year period from April 1, 1995, to June 30, 2022. Among 3 761 618 Danish residents younger than 20 years, cases were individuals who experienced an SOE. For each case, there were 10 matched population-based controls without a prior SOE. Household family members were individually linked to case and control participants. Statistical analyses were performed between August 2024 and January 2025.

EXPOSURE: An analgesic prescription filled by a household family member within 3 months before a child’s SOE. The study included 3 categories of children whose family members were (1) exposed to prescription opioids, (2) exposed to nonsteroidal anti-inflammatory drugs (NSAIDs), and (3) unexposed.

MAIN OUTCOME AND MEASURES: SOE, defined as death, hospitalization, or emergency department visit due to opioid intoxication. The incidence rate ratio of SOEs among children whose family members redeemed an opioid prescription was compared with those in unexposed households and with those whose family members filled NSAID prescriptions. Conditional logistic regression was used to compute adjusted odds ratios (AORs), controlling for potential sociodemographic and mental health confounders. Subsequently, analyses were stratified by sex, age brackets (<13 vs ≥13 years), SOE calendar year, and hospital disposition. Finally, a sensitivity analysis was conducted restricting the interval between prescription dispensing and the SOE to 1 month.

RESULTS: A total of 2000 children (median age at SOE, 17.8 years [IQR, 15.7-19.0 years]; 1096 boys [54.8%]) experienced an SOE and were matched with 19 840 controls (median age at index, 17.7 years [IQR, 15.6-19.0 years]; 10 872 boys [54.8%]). Among 2000 cases, 1116 (55.8%) were hospitalized and 60 (3.0%) died. Having a family member fill an opioid prescription (319 cases and 1137 controls) was associated with increased odds of an SOE compared with unexposed children (1398 cases and 16 181 controls; AOR, 2.87; 95% CI, 2.45-3.38) and with children exposed to NSAIDs (283 cases and 2522 controls; AOR, 2.22; 95% CI, 1.81-2.72). Odds of an opioid-related death were nearly 4-fold higher compared with unexposed children (15 cases and 33 controls vs 42 cases and 496 controls, respectively; AOR, 3.70; 95% CI, 1.55-8.84). The association remained robust in stratified and sensitivity analyses.

CONCLUSIONS AND RELEVANCE: This study suggests that children of family members prescribed opioids had increased odds of opioid intoxication-related death and other SOEs compared with children of unexposed families or those exposed to nonopioid analgesics. Public health strategies to mitigate the opioid crisis should consider unique pediatric aspects that can reduce the likelihood of pediatric SOEs.

PMID:41885863 | DOI:10.1001/jamanetworkopen.2026.3515

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Trends in Mammography Use Among Women Aged 40 to 74 Years in the US, 2002-2022

JAMA Netw Open. 2026 Mar 2;9(3):e263529. doi: 10.1001/jamanetworkopen.2026.3529.

ABSTRACT

IMPORTANCE: Understanding how prior policies, systemic factors, and public health events have shaped mammography use among US women is essential for interpreting the 2024 US Preventive Services Task Force (USPSTF) recommendation update and identifying gaps to inform equitable public health strategies.

OBJECTIVE: To analyze mammography use trends in US women aged 40 to 49 and 50 to 74 years from 2002 to 2022 and assess variation by sociodemographic, health care access, behavioral, and geographic factors, including associations with the 2009 USPSTF recommendation and the COVID-19 pandemic.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from the Behavioral Risk Factor Surveillance System biennial cancer screening module (2002-2022). Joinpoint regression with a jump model was used to account for methodological changes in the Behavioral Risk Factor Surveillance System beginning in 2011. Data were analyzed from March to September 2025.

MAIN OUTCOMES AND MEASURES: The primary outcome was the average biennial percentage change in mammography use from 2002 to 2022, calculated as a weighted average of jump model-estimated biennial changes. Subgroup analyses were conducted by sociodemographic, health care access, behavioral, and geographic factors.

RESULTS: Among 2 619 292 US women, mammography use showed a downward trend, with nonsignificant biennial changes of -0.54% (95% CI, -1.25% to 0.16%) for ages 40 to 49 years and -0.16% (95% CI, -0.49% to 0.16%) for ages 50 to 74 years from 2002 to 2022. Declines were significant among young women without health insurance (-1.54%; 95% CI, -2.89% to -0.17%), current smokers (-1.36%; 95% CI, -2.43% to -0.27%), unmarried women (-1.10%; 95% CI, -1.61% to -0.59%), and non-Hispanic White women (-0.58%; 95% CI, -1.09% to -0.07%). Following the 2009 USPSTF recommendation, mammography use decreased significantly among younger non-Hispanic White (-0.88%; 95% CI, -1.59% to -0.16%), Asian (-2.45%; 95% CI, -4.20% to -0.25%), and uninsured (-2.39%; 95% CI, -4.57% to -0.16%) women, with no significant reduction among non-Hispanic Black women (-0.59%; 95% CI, -1.20% to 0.03%). Across both age groups, mammography use was consistently lower in Western than in Eastern states.

CONCLUSIONS AND RELEVANCE: In this cross-sectional study, mammography use did not significantly decline in the overall population; however, significant reductions were observed among non-Hispanic White, Asian, and uninsured women aged 40 to 49 years from 2010 to 2022. These findings highlight the need for clear, risk-based screening communication and targeted strategies to promote guideline-concordant decision-making, particularly among younger women.

PMID:41885862 | DOI:10.1001/jamanetworkopen.2026.3529

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Socioeconomic Status, Rurality, and Pediatric Critical Care Admission

JAMA Netw Open. 2026 Mar 2;9(3):e263594. doi: 10.1001/jamanetworkopen.2026.3594.

ABSTRACT

IMPORTANCE: Neighborhood-level socioeconomic deprivation has been associated with higher incidence and severity of pediatric critical illness; however, structural factors underlying observed differences have received limited attention.

OBJECTIVE: To describe the association between area-level deprivation, rurality, and incidence of critical care admission among children.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used linked data of individuals aged 0 to 17 years who were admitted to intensive care units in British Columbia (BC), Canada, between 2014 and 2023. Data were analyzed from June to November 2025.

EXPOSURES: Age, sex, rurality, and neighborhood situational vulnerability (a measure of socioeconomic disadvantage).

MAIN OUTCOMES AND MEASURES: The primary outcome was the incidence rate of critical care admission. Poisson regression models were used to estimate incidence rate ratios (IRRs) between exposure groups. The possible interaction between situational vulnerability quintile and population center type was examined.

RESULTS: A total of 10 048 children were admitted 13 990 times to intensive care units (incidence rate of 154 per 100 000 person years). Most admissions were for male children (7641 [54.6%]) and children younger than 5 years (7528 [53.8%]). The IRR for rural or small population centers compared with medium or large was 1.35 (95% CI, 1.28-1.41). Similarly, the IRR for the most vs least deprived quintile was 1.31 (95% CI, 1.23-1.39); however, in medium or large population centers, there was no association between situational vulnerability quintile and critical care admission (eg, quintile 5 vs 1: IRR 1.04; 95% CI, 0.97-1.12). Those in rural or small areas of the most deprived quintile had the highest overall rate (IRR, 2.02; 95% CI, 1.87-2.19 vs highest quintile in large or medium population centers).

CONCLUSIONS AND RELEVANCE: In this retrospective cohort study there was higher burden of critical care admission for children living in rural areas and small population centers, and areas with higher situational vulnerability. The association between situational vulnerability and critical care incidence was unique to rural or small regions. Targeted strategies are needed to address contributing factors and ensure timely access to pediatric acute care in underserved areas.

PMID:41885861 | DOI:10.1001/jamanetworkopen.2026.3594

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Maternal Nativity and Residence in US Territories and Preterm Birth

JAMA Netw Open. 2026 Mar 2;9(3):e263601. doi: 10.1001/jamanetworkopen.2026.3601.

ABSTRACT

IMPORTANCE: US territory nativity and/or residence may be associated with health because it affects environmental exposures, insurance coverage, prenatal care, and other factors. Investigations of preterm birth in the US territories are limited.

OBJECTIVE: To assess the association between maternal territory status and preterm birth, as well as whether insurance type modified associations.

DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study of restricted-use birth certificates of in-hospital, singleton births in the US and territories from 2014 to 2023.

EXPOSURES: Maternal territory status was defined for births in territories where data were available (Guam, Northern Mariana Islands, Puerto Rico, and Virgin Islands) for the following groups: (1) those with territory nativity and residence; (2) those with territory nativity and mainland residence; (3) those with mainland nativity and territory residence; and (4) those with mainland nativity and residence (reference group). Insurance type (private, Medicaid, or other) was evaluated as well.

MAIN OUTCOMES AND MEASURES: Preterm birth (live birth before 37 weeks’ gestation).

RESULTS: Among 28 627 700 births, 465 291 (1.6%) had any maternal territory status (nativity or residence). This group had a mean (SD) age of 27.1 (6.0) years, and 297 593 (64.0%) had Medicaid insurance. The highest preterm birth rate was among those with territory nativity and residence (10.5%; 95% CI, 10.4%-10.7%); the lowest was among those with mainland nativity and residence (8.4%; 95% CI, 8.4%-8.5%). Individuals with territory nativity and residence had an adjusted relative risk (aRR) of 1.30 (95% CI, 1.29-1.32) for preterm birth compared with the reference group. There was significant interaction between territory residence and insurance. Compared with individuals with mainland residence and private insurance, those with territory residence and Medicaid had the highest preterm birth risk (aRR, 1.57; 95% CI, 1.55-1.59), followed by territory residence and private insurance (aRR, 1.42; 95% CI, 1.39-1.45).

CONCLUSIONS AND RELEVANCE: In this cross-sectional study, maternal territory nativity and residence were associated with preterm birth. Territory residence was associated with a higher risk of preterm birth, regardless of insurance type. Privately insured-individuals in US territories had a higher risk of preterm birth than Medicaid-insured individuals in the mainland. Given differential access to health care, health insurance, and other social exposures between territory and mainland populations, future work should explore causal effects and related policies that may improve birth outcomes in US territories.

PMID:41885860 | DOI:10.1001/jamanetworkopen.2026.3601

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Personality, Jealousy, and Empathy as Predictors of Cyber Dating Abuse Perpetration and Victimization in Young Adults

Psychol Rep. 2026 Mar 26:332941261436663. doi: 10.1177/00332941261436663. Online ahead of print.

ABSTRACT

Cyber dating abuse involves psychological and relationally harmful behaviours enacted through digital technologies within romantic relationships. Although prior research links dispositional variables to cyber dating abuse, perpetration and victimisation frequently co-occur, complicating the interpretation of individual differences. This study examined associations among personality traits, romantic jealousy, empathy, and gender with psychological and relational cyber dating abuse perpetration and victimisation in 503 young adults aged 18 to 25 in the UK. Hierarchical regression analyses accounted for overlap across forms of cyber dating abuse involvement. Psychological and relational perpetration and victimisation were strongly interrelated, with other forms of involvement accounting for most explained variance across models. After modelling this overlap, dispositional variables explained small but statistically significant increments in variance, with behavioural jealousy and lower agreeableness most consistently associated with perpetration. Dispositional variables did not meaningfully predict psychological victimisation, and gender effects were modest and inconsistent. Overall, the findings suggest cyber dating abuse is best understood as a relational phenomenon characterised by co-occurring perpetration and victimisation, with individual differences shaping how behaviours are expressed rather than serving as primary drivers.

PMID:41885857 | DOI:10.1177/00332941261436663