Tag: statistics

Med Biol Eng Comput. 2026 Jul 3. doi: 10.1007/s11517-026-03618-9. Online ahead of print.

ABSTRACT

The hemoglobin concentration in blood is vital for diagnosing anemia and monitoring the various health conditions. However, conventional measurement methods need invasive blood sampling so that they might have limited accessibility and uncomfortable for patients. Today, non-invasive alternatives powered by machine learning techniques provide promising solutions for point-of-care facilities and remote healthcare systems. This paper presents a methodology through a comprehensive research and development process to estimate hemoglobin levels from facial videos using multi-modal feature extraction and ensemble learning techniques. A dataset of 260 participants with various blood hemoglobin levels was processed to extract the features from pre-trained convolutional neural-networks (MobileNetV2, ResNet152), remote photoplethysmography (rPPG) signals, and color statistical features. Using these features, hemoglobin concentration was estimated via a number of machine learning models including XGBoost, Random Forest, and Stacking Regressor, respectively. Stacking Regressor provided the best estimation scores with a mean-absolute error of 0.7754 g/dL, Pearson correlation-coefficient of 0.7878, and [Formula: see text] score of 0.5852. ResNet152 model based features were combined with XGBoost, which achieved comparable performance (MAE: 0.6635 g/dL, [Formula: see text]: 0.4977). Experimental results demonstrated that multi-modal feature strategy outperformed single-modality approaches in terms of prediction accuracy and robustness. The proposed video-based estimation of hemoglobin concentration system achieves clinically relevant accuracy levels, outperforms to literature methods, comparable to point-of-care instruments demonstrating strong potential for use in anemia screening and remote patient monitoring.

PMID:42393483 | DOI:10.1007/s11517-026-03618-9

Drug Saf. 2026 Jul 2. doi: 10.1007/s40264-026-01693-3. Online ahead of print.

ABSTRACT

BACKGROUND: Medication shortages are a considerable and ongoing issue in healthcare, disrupting consumer access to medicines. Since 2021, Australia’s national medicines regulator has issued Serious Scarcity Substitution Instruments (SSSIs), allowing pharmacists to substitute a specific therapeutically equivalent strength and/or formulation of a medicine without prior approval from a prescriber. The impact of SSSIs on utilisation of medicines has not been investigated.

OBJECTIVE: To determine whether SSSIs are effective in addressing medicine shortages and meeting patients’ needs.

METHODS: This retrospective cohort study used aggregated pharmacy claims to examine the utilisation of 12 medicines, which had an SSSI. We calculated the percentage change in defined daily doses dispensed per 1000 population per day in the 11 months after SSSI implementation, compared with the previous 2 years. A percentage change of less than 20% was used to indicate success.

RESULTS: Following medicine shortages, utilisation fell for 10 of the 12 medicines examined. For eight of these medicines (amoxicillin, cefalexin, estradiol, fluoxetine, insulin degludec with insulin aspart, isosorbide mononitrate, vigabatrin, and warfarin) decreases in utilisation were minimised to < 20%. On average, SSSIs where all permitted substitute products were scarce (e.g., abatacept) were associated with larger decreases in use (between – 22 and – 68%) than those for which none or only some of the substitutes were in shortage (between – 45 and + 7%, respectively).

CONCLUSIONS: While product shortages led to decreases in medicines consumption, SSSIs appeared to be successful in limiting decreases. However, SSSIs were less likely to be successful when many of the permitted substitute products were also scarce.

PMID:42393456 | DOI:10.1007/s40264-026-01693-3

J Magn Reson Imaging. 2026 Jul 2. doi: 10.1002/jmri.70431. Online ahead of print.

ABSTRACT

BACKGROUND: Susceptibility alterations in deep gray matter (DGM) nuclei after acute ischemic stroke (AIS) may relate to impaired functional independence. However, conventional quantitative susceptibility mapping (QSM) cannot separate paramagnetic iron-related from diamagnetic myelin-related sources, potentially obscuring relevant pathophysiological alterations.

PURPOSE: To apply χ-separation to disentangle paramagnetic susceptibility (χ_para) and diamagnetic susceptibility (χ_dia) in DGM nuclei after AIS and assess associations with 3-month functional independence.

STUDY TYPE: Prospective.

POPULATION: 82 AIS patients (52 M/30 F) and 82 healthy controls (49 M/33 F).

FIELD STRENGTH/SEQUENCE: 3 T; 3D multi-echo gradient-echo sequence for QSM and χ-separation reconstruction.

ASSESSMENT: χ_para and χ_dia were measured in the caudate, putamen, globus pallidus, substantia nigra, red nucleus, thalamus, and dentate nucleus. Contralesional nuclei were analyzed in patients. Group differences and 3-month outcome associations were assessed. Functional independence was defined as modified Rankin Scale score 0-2, and poor outcome as 3-6.

STATISTICAL TESTS: Linear mixed-effects models, analysis of covariance, logistic regression, receiver operating characteristic analysis; p < 0.05 was significant.

RESULTS: Compared with healthy controls, patients showed higher χ_para in all seven nuclei, including the dentate nucleus (84.065 ± 15.086 vs. 76.172 ± 11.387 ppb) and thalamus (30.633 [28.036, 34.454] vs. 28.867 [26.749, 31.804] ppb), and higher χ_dia in the caudate, putamen, red nucleus, thalamus, and dentate nucleus (dentate nucleus: -18.916 ± 6.496 vs. -22.220 ± 5.002 ppb). Poor 3-month outcome was independently associated with higher dentate nucleus χ_para (OR, 1.07; 95% CI, 1.03-1.11), higher dentate nucleus χ_dia (OR, 1.14; 95% CI, 1.04-1.26), and higher thalamus χ_para (OR, 1.22; 95% CI, 1.08-1.38). The combined model, incorporating conventional model factors (age, sex, stroke subtype, NIHSS score, and infarct volume) and χ-separation metrics, outperformed the conventional model (AUC, 0.862 vs. 0.757).

DATA CONCLUSION: χ-separation revealed iron- and myelin-related susceptibility alterations in contralesional DGM nuclei after AIS. Susceptibility metrics in the dentate nucleus and thalamus were associated with poor 3-month functional outcome.

EVIDENCE LEVEL: 2.

TECHNICAL EFFICACY: Stage 1.

PMID:42393438 | DOI:10.1002/jmri.70431

Diabetologia. 2026 Jul 2. doi: 10.1007/s00125-026-06790-7. Online ahead of print.

ABSTRACT

AIMS/HYPOTHESIS: The aim of this study was to examine whether the independent and joint effects of obesity and alcohol consumption on diabetes risk differ when exposures are assessed at baseline or as time-varying variables, and whether interaction patterns vary across multiplicative and additive scales in a Asian prospective cohort.

METHODS: In total, 7817 participants aged ≥40 years without diabetes at baseline (2001-2002) were followed until 2017-2018, and the associations of obesity and alcohol consumption with incident diabetes and their interactions were assessed using Cox proportional hazards and Aalen’s additive hazards models.

RESULTS: Obesity and high alcohol consumption (≥30 g/day) were consistently associated with incident diabetes across all analyses, with stronger associations observed in the time-varying models. Obesity (HR 1.91; 95% CI 1.75, 2.09; 21.9 additional cases per 1000 person-years; 95% CI 20.0, 23.8) and high alcohol consumption (HR 1.23; 95% CI 1.05, 1.44; 14.6 additional cases per 1000 person-years; 95% CI 11.1, 18.1) were both associated with increased diabetes risk. Associations for low-to-moderate alcohol consumption were weaker, and were statistically significant only on the additive scale. No significant multiplicative interactions were observed for the effect of baseline or time-varying obesity, current alcohol consumption or daily alcohol consumption on the risk of diabetes. However, significant antagonistic additive interactions were observed between baseline or time-varying obesity and current alcohol consumption: drinking <10 g/day with 12.8 fewer cases/1000 person-years (95% CI -17.4, -8.2), 10-29.9 g/day with 15.9 fewer cases (95% CI -22.1, -9.8), and ≥30 g/day with 14.6 fewer cases (95% CI -22.0, -7.2), with a p_interaction value <0.001. Joint analysis revealed that, in participants with obesity, the increased association with low-to-moderate alcohol consumption was minimal in terms of multiplicative and additive models, especially for time-varying exposures. The results were comparable in the sensitivity analysis that was restricted to baseline current drinkers, in which current drinkers consuming <10 g/day of alcohol were used as the reference group.

CONCLUSIONS/INTERPRETATION: Obesity and high alcohol consumption were consistently associated with incident diabetes, and an antagonistic additive interaction was observed between obesity and all alcohol consumption levels. These findings highlight the importance of exposure modelling and scale choice, and support prioritising weight management and reducing high alcohol consumption in diabetes prevention.

PMID:42393406 | DOI:10.1007/s00125-026-06790-7

Diabetologia. 2026 Jul 2. doi: 10.1007/s00125-026-06788-1. Online ahead of print.

ABSTRACT

AIMS/HYPOTHESIS: In healthy lean humans, endogenous glucose-dependent insulinotropic polypeptide (GIP) contributes significantly to the postprandial increase in arteria mesenterica superior blood flow. The vascular biology related to activation of the GIP receptor is markedly impaired in individuals with type 2 diabetes and is sometimes absent. In this population, we investigated the role of endogenous GIP on postprandial splanchnic blood flow by using the GIP receptor antagonist, GIP(3-30)NH₂. The primary outcome of this study was the changes in blood flow in arteria mesenterica superior during oral glucose with or without GIP receptor antagonist infusion.

METHODS: Ten participants with type 2 diabetes (age 20-80 years, BMI 20-35 kg/m², and HbA_1c >48 mmol/mol and <75 mmol/mol) were investigated in a randomised, placebo-controlled, crossover study. On four separate occasions, participants received the following treatment: oral glucose + i.v. GIP(3-30)NH₂; oral glucose + i.v. saline (154 mmol/l NaCl); oral water + i.v. GIP(3-30)NH₂; oral water + i.v. saline. Participants were randomly assigned to intervention groups using (random.org). Participants were unaware of allocation, while investigators were aware. No additional allocation concealment procedures were used. During all four interventions, splanchnic blood flow was measured using phase-contrast MRI in the arteria mesenterica superior, truncus coeliacus and vena portae during oral glucose (75 g) or water ingestion. The study was conducted at Rigshospitalet, Copenhagen. Liver volume and oxygenation, as well as gallbladder volume, were assessed. Blood samples were collected and analysed for insulin, C-peptide, GIP, glucagon and glucose.

RESULTS: Oral glucose alone increased mean blood flow in arteria mesenterica superior by 57% (95% CI 26, 88) and this was 15% (95% CI -2, 32) lower during concomitant GIP receptor antagonist infusion, p=0.012. Infusion of GIP receptor antagonist during oral glucose treatment did also result in lower insulin secretion, C-peptide and C-peptide/glucose ratio compared with saline infusion, whereas glucagon levels and plasma glucose were unaffected. Oral water did not affect any outcomes.

CONCLUSIONS/INTERPRETATION: Endogenous GIP contributes to postprandially increased splanchnic blood flow in people with type 2 diabetes.

TRIAL REGISTRATION: ClinicalTrials.gov NCT06426823 FUNDING: This work was supported by the Novo Nordisk Foundation.

PMID:42393405 | DOI:10.1007/s00125-026-06788-1

Stat Med. 2026 Jul;45(15-17):e70654. doi: 10.1002/sim.70654.

ABSTRACT

The human microbiome plays a crucial role in health, but understanding its dynamic relationship with the host requires regular monitoring. Beyond challenges such as high dimensionality and sparsity, additional complexities arise, particularly within-cluster correlation from repeated measures and pervasive missing data. To address these issues, we develop Edger, a novel distance regression method for modeling community-level beta-diversity dynamics and their interactions with treatment or host physiology. By focusing on beta-diversity, a distance metric between microbial profiles, Edger (Ensembled semiparametric distance-based generalized estimation for repeated outcomes) directly models these distances as repeated outcomes, yielding interpretable coefficients and enabling a covariate batching strategy to mitigate omitted variable bias. Our semiparametric inference framework eliminates the need for time-consuming permutation tests, distinguishes between-cluster heterogeneity from within-cluster fluctuations, and allows flexible specification of working correlation structures. To handle missing data, we assume a missing-at-random (MAR) mechanism and incorporate a between-subject propensity score in the repeated distance regression to provide seamless joint inference, ensuring robust variance estimation without casewise deletion. Additionally, we introduce an algorithm to generate synthetic data from real-world microbial counts while preserving their zero-inflated and correlated nature. Edger demonstrates superior inferential power and computational efficiency through our numerical studies and real-world applications, making it a valuable tool for uncovering microbiome-host interactions and advancing multi-omics data integration.

PMID:42393392 | DOI:10.1002/sim.70654

Environ Geochem Health. 2026 Jul 2;48(10):430. doi: 10.1007/s10653-026-03332-3.

ABSTRACT

Improper discharge of untreated textile effluents comprising synthetic azo-dyes which are characterised by azo bond (-N = N-), poses severe environmental and public health concern due to persistence, toxicity and resistance towards conventional treatment techniques. This has created pressing need for low-cost, eco-friendly alternatives where microbial degradation shows effective remediation compared to chemical and physicochemical treatment methods, which are often costly, energy-intensive, and generate secondary pollutants. In this study, novel azoreductase-producing bacterium, Brevundimonas sp. AJZ05, was isolated from textile effluent and exhibited initial Direct Blue-6 decolorization efficiency of 85.24% and azoreductase activity of 0.172 U/mL. Plackett Burman design identified dye concentration, yeast extract, inoculum level as key variables influencing decolorization efficiency, while glucose, yeast extract, and inoculum level significantly affected azoreductase activity. Multi-response optimization via Response Surface Methodology with desirability functional approach determined optimal conditions: dye concentration (101.76 mg/L), glucose (5.19 g/L), yeast extract (5.87 g/L), and inoculum level (5.45%), achieving maximum decolorization efficiency (98.50%) and azoreductase activity (0.761 U/mL), corresponding to 1.1-fold and 2.83-fold increases, respectively. The optimized process remained effective in the presence of metal ions (Cu²⁺, Mg²⁺, Mn²⁺, Zn²⁺, Fe²⁺ at 0.5-1 mM), indicating its robustness under effluent condition. UV-Vis spectroscopy, FTIR, GC-MS and phytotoxicity analysis using Vigna radiata confirmed complete breakdown of DB-6 into less/non-toxic intermediates. Overall, Brevundimonas sp. AJZ05 exhibits strong potential for azo-dye bioremediation and toxicity reduction, showing significant promise towards environmental sustainability.

PMID:42393388 | DOI:10.1007/s10653-026-03332-3

Arch Environ Contam Toxicol. 2026 Jul 2;91(1):8. doi: 10.1007/s00244-026-01206-4.

ABSTRACT

In this study we provide a comprehensive assessment of metal contamination in the Amazon River and its main tributaries, with a focus on urban contamination hotspots. A monitoring campaign was conducted across 40 sampling sites, analysing water concentrations of As, Cd, Cu, Cr, Fe, Mn, Pb, Ni, and Zn. Metal concentrations were evaluated against national and international water quality standards and compared between urbanized and less impacted regions to delineate pollution patterns. Additionally, an ecological risk assessment was conducted for individual metals and for metal mixtures using Species Sensitivity Distributions (SSDs). The results of this study show that Fe levels in the Amazon River were exceptionally high, with potential implications for aquatic species distribution across the basin. Exceedances of water quality standards were identified for four metals (Fe, Pb, Mn, Cu), with metal enrichment observed particularly in Manaus, Macapá, and Belém. Acute multi-substance potentially affected fraction (msPAF) of species in the Amazon River and its tributaries indicated insignificant risks, while chronic values ranged from 3% to 33%. In urban areas, acute msPAF values were generally low, with the exception of two samples taken in Manaus that exhibited values of 11% and 16%. Chronic riskvalues, however, were consistently high in these urban locations, reaching up to 72% of species potentially affected and reflecting sustained ecotoxicological stress. Cu, Zn and Mn were identified as the primary contributors to chronic toxicity, with Cu and Zn dominating in Manaus, and Mn in Macapá. These findings underscore the need for stricter industrial discharge regulations and improved wastewater treatment systems to preserve Amazonian freshwater ecosystems.

PMID:42393378 | DOI:10.1007/s00244-026-01206-4

Sci Rep. 2026 Jul 2. doi: 10.1038/s41598-026-60446-5. Online ahead of print.

ABSTRACT

Alzheimer’s disease is associated with progressive cognitive, functional and social decline. Non-pharmacological interventions that combine cognitive and motor stimulation are increasingly used in long-term care, but less is known about the feasibility and preliminary effects of delivering such programmes in outdoor rather than indoor settings. This exploratory randomized single-blind pilot study compared outdoor and indoor cognitive-motor therapy in institutionalized older women with Alzheimer’s disease, focusing on global cognitive performance, selected functional outcomes, attendance and practical implementation. Fifty women aged 66.1-70.2 years with late-onset Alzheimer’s disease were randomized to a seven-month outdoor cognitive-motor programme (n = 25) or an indoor cognitive-motor programme (n = 25). Sessions were delivered five times weekly for 45 min. Outcome assessors and data analysts were blinded to group allocation; therapists and participants could not be blinded because of the intervention setting. Global cognition was assessed with the Mini-Mental State Examination (MMSE). Functional outcomes were assessed using modified FIM-based indicators for daily tasks, mobility and social adaptability. Attendance and adverse events were recorded as feasibility outcomes. All randomized participants completed the study. Mean attendance was 91% in the outdoor group and 89% in the indoor group, and no intervention-related adverse events were recorded. Both groups improved on the MMSE, with a median increase of approximately two points. The outdoor group showed statistically significant within-group improvements in all three FIM-based indicators (daily tasks, mobility and social adaptability), whereas the indoor group did not show statistically significant functional change. However, these broader gains were observed in the context of baseline functional imbalance, including lower outdoor-group mobility and social-adaptability scores, and the small female-only sample and partial non-equivalence of intervention content limit between-group causal interpretation. A seven-month cognitive-motor programme was feasible in participating long-term care facilities. The findings suggest that outdoor delivery may be associated with broader functional gains than indoor delivery, but the results should be interpreted as preliminary and in light of the baseline functional imbalance. A fully powered, prospectively registered trial with more equivalent intervention arms, repeated measurement points, standardized functional outcomes and detailed monitoring of comorbidities and medication changes is warranted.

PMID:42393367 | DOI:10.1038/s41598-026-60446-5

Sci Rep. 2026 Jul 2. doi: 10.1038/s41598-026-59783-2. Online ahead of print.

ABSTRACT

Urinary incontinence, coital incontinence, dyspareunia, and sexual dysfunction are clinical conditions that can result from this condition. Treatment options include conservative and surgical approaches. The gold standard in surgery is mid-urethral sling procedures. The aim of this study is to compare the effects of the commonly used conventional transobturator tape (TOT) and retropubic transobturator tape (TOTRP) techniques on female sexual function and to evaluate possible differences, particularly regarding dyspareunia. A total of 108 sexually active women with stress urinary incontinence who underwent conventional TOT (n = 54) or TOTRP (n = 54) surgery between January 2023 and January 2025 were included in the study. Women aged 18-60 years who presented to the clinic for stress urinary incontinence between January 2023 and January 2025, were sexually active, underwent TOT or TOTRP surgery, and had a minimum of 6 months postoperatively were included in the study. The FSFI questionnaire data and demographic characteristics of patients in this group, as routinely collected in our practice, were retrieved from the hospital database and patient files. Data analysis and statistics were performed using jamovi software (version 2.6.44). No significant differences were found between the demographic and clinical characteristics of the two groups included in the study. A significant increase in postoperative FSFI scores was observed in both groups compared to the preoperative period. No significant difference was found between TOT and TOTRP in terms of total FSFI scores. However, when FSFI subscales were examined, a significant improvement in dyspareunia scores was observed only in the TOTRP group in the postoperative period (p < 0.001). No significant change in dyspareunia was observed in the conventional TOT group. Postoperative coital incontinence decreased significantly in both groups. Conventional TOT and TOTRP techniques provide a general improvement in female sexual function after SUI surgery. Although there is no significant superiority between the techniques in terms of total sexual function scores, improvement in dyspareunia scores was observed in the TOTRP group; however, direct superiority over conventional TOT could not be established. Prospective, randomized, long-term follow-up studies are needed to confirm these findings.

PMID:42393323 | DOI:10.1038/s41598-026-59783-2