Physiological Reports

While the need for continuous blood pressure (BP) monitoring in Japan is high, there are no commercially available cuffless devices for personal daily monitoring use. Fingertip-based sensors are a promising alternative as they eliminate the discomfort of repeated cuff inflation. However, their reliability during winter has been a major technical limitation due to cold-induced peripheral vasoconstriction. This study aimed to address this issue by validating a novel fingertip-based continuous BP monitor used by exercising adults during summer and winter. Eleven community-dwelling older adults (mean age, 73.1 {+/-} 8.8 years) were included in this seasonal comparative study. During exercise, we compared a personal fingertip-based continuous monitor (ArteVu) with a standard oscillometric cuff device (Omron) in summer (mean, 26.5{degrees}C) and winter (mean, 7.4{degrees}C). The study also evaluated the device's accuracy during exercise-induced BP fluctuations and seasonal environmental changes. Awareness of the participants regarding BP management was also assessed using questionnaires. There were strong correlations for systolic BP (SBP) between summer and winter (r = 0.93 in summer; r = 0.88 in winter). Although the mean difference for the SBP was higher in winter than in summer (3.1 {+/-} 11.2 mmHg vs. 0.2 {+/-} 9.4 mmHg), the values remained within a clinically acceptable range for personal monitoring. Notably, 72.7% of participants reported that the ease of using the fingertip-based device significantly increased their awareness and motivation for daily BP management. This study confirms the feasibility of cuffless fingertip-based continuous BP monitoring across different seasons, including in winter. By overcoming the seasonal limitations, this device fills a critical gap in the Japanese health-monitoring market. Our findings support the development of smaller and more portable models, representing a shift from traditional "snapshot" cuff measurements to continuous and integrated lifestyle monitoring for older adults.

Objective: Skin sympathetic nerve activity (SKNA) has emerged as a promising non-invasive surrogate measure of sympathetic drive, but its relevant physiological characteristics remain ill-defined. This observational study aims to investigate its regulatory patterns during rest and Valsalva maneuver (VM) in healthy participants. Method: Using a two-layer strategy integrating signal analysis and physiological modelling, we analyzed data recorded from 41 subjects performing repeated VMs. The observational layer includes time-domain feature comparisons using linear mixed-effect models, and time-varying spectral coherence analysis. The mechanistic layer proposes a mathematical model to investigate whether baroreflex and respiratory modulation are sufficient to reproduce the observed HR and average SKNA (aSKNA) dynamics. Main Results: Mean integrated SKNA (iSKNA) showed more significant change than HRV for VM induced effects. We also found mean iSKNA increase during VM varies with BMI and sex. The coherence analysis indicated that iSKNA strongly synchronized with EDR under resting conditions. The proposed model successfully reproduced main characteristics of aSKNA dynamics, yielding a high median Pearson correlation coefficient of 0.80 ([Q1, Q3] = [0.60, 0.91]). In contrast, HR dynamics were only partially captured, with a median PCC of 0.37 ([Q1, Q3] = [0.16, 0.55]). These results likely suggest SKNA provides a more direct representation of sympathetic burst dynamics during VM in healthy subjects. Significance: This study provides convergent evidence that SKNA reflects known autonomic regulatory influences in healthy subjects. These findings strengthen the physiological interpretability of SKNA while clarifying its appropriate use as a practical biomarker of sympathetic function.

Background/Objective: Common measures of physical activity (PA) based on duration and intensity do not fully capture its complexity. Adding additional PA components of muscle strength, mechanical strain, and turning actions, can provide a more complete view of activity behavior. Furthermore, PA behaviors differ between men and women. Therefore, the goal of this study is to identify and cluster similar long-term PA patterns over time for each PA component, examined separately for men and women. Methods: We used data from 4963 participants (52% women; mean age 66 years, SD = 8.6) of the Longitudinal Aging Study Amsterdam (1992 to 2019). PA component scores were assigned to self-reported activities, and Sequence Analysis with Optimal Matching was used to identify and cluster similar activity patterns over a period of 10 years, separately for each component and stratified by sex. Results: PA components varied by sex and displayed a unique mix of trajectories, including predominately low, medium, or high activity, increasing or decreasing patterns, and trajectories characterized by early or late mortality. Importantly, trajectories remained independent, indicating that changes in one PA component were not linked to changes in others. Conclusion: Older men and women follow distinct and independent long term PA trajectories across components, underscoring that PA behaviour cannot be described by a single dimension. Significance/Implications: The observed independence and heterogeneity of trajectories suggest that muscle strength, mechanical strain, and turning actions capture meaningful and distinct aspects of PA that are not reflected by traditional measures alone. Future PA-strategies could incorporate these dimensions and acknowledge sex-specific patterns to better reflect natural movement. The independence of components suggests that future interventions should target multiple dimensions, as changes in one component may not translate to others. Such an approach may support more tailored and sustainable PA interventions in later life.

Rationale: Sepsis is a life-threatening syndrome causing significant morbidity and mortality especially in the aging population. Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition of clonal expansion of hematopoietic stem cells harboring somatic mutations associated with increased incidence of chronic illness and all-cause mortality. Objective: Evaluate the association of pre-illness CHIP with mortality and morbidity in patients admitted to the ICU with sepsis. Methods: We performed a retrospective study using a de-identified electronic health record linked with a DNA biorepository. We identified adult patients with sepsis who had DNA collected prior to ICU admission. We tested the association between CHIP status, determined from whole-genome sequencing, and ICU mortality, organ support-free days, and long-term survival adjusting for age, sex, race and Sequential Organ Failure Assessment (SOFA) score on ICU admission. Measurements and Main Results: Pre-illness CHIP was associated with increased sepsis mortality (OR = 1.54, 95% CI 1.13 to 2.07, P = 0.005) and fewer days alive and free of organ support (-1.7 days, 95% CI -3.2 to -0.2, P = 0.028) after adjusting for age, sex, race, and SOFA score. In sepsis survivors, CHIP was also associated with increased long-term mortality after discharge (HR 1.40, 95% CI 1.01 to 1.93, P = 0.041). Conclusions: Pre-illness CHIP was independently associated with increased mortality and morbidity in critically-ill adults with sepsis. These findings suggest that CHIP is a risk factor for sepsis severity. Elucidating the mechanism underlying this association could uncover new therapeutic interventions for sepsis.

Walking impairments in Parkinsons disease (PD), including reduced speed, cadence, and stride length, and increased variability, impair mobility and raise fall risk. Conventional treatments may fail to address these deficits, underscoring the need for complementary non-invasive alternatives. This study examined whether combining rhythmic auditory cueing with transcranial direct current stimulation (tDCS) over the supplementary motor area (SMA), a critical region for internally-generated movement, would enhance gait performance in PD. Thirty-three participants with PD and thirty-two healthy controls completed two sessions (anodal vs. sham tDCS) with gait assessed during stimulation, immediately after stimulation, and 15 minutes after stimulation under two auditory conditions: walking in silence and walking to music paced 10% faster than baseline cadence. Spatiotemporal, variability, and stability gait parameters were analyzed using linear mixed-effects models. Rhythmic auditory cueing significantly increased cadence and speed during, immediately after, and especially 15 minutes after stimulation, suggesting sustained effects of rhythmic entrainment. Anodal tDCS produced faster cadence, as well as lower stride time variability and stride width, particularly in individuals with PD. Although both music and anodal tDCS affected gait, no interaction was observed, indicating independent effects. Individuals with PD had greater gait variability overall, and adjusted temporal gait parameters less to music than healthy controls did. Anodal stimulation reduced walking variability in PD, reducing the group differences observed under sham conditions. These findings suggest that rhythmic cueing and SMA stimulation target complementary mechanisms, highlighting the promise of combined tDCS-music interventions for gait rehabilitation in PD.

ObjectivesAlarm fatigue is a patient safety concern in ICUs, yet no validated instrument exists to assess alarm fatigue among healthcare professionals in non-Western settings. This study aimed to cross-culturally adapt the Charite Alarm Fatigue Questionnaire (CAFQa) into Japanese and evaluate its reliability and validity among ICU nurses and physicians. MethodsThe Japanese CAFQa was cross-culturally adapted following the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines, including forward translation, back-translation, expert panel review, and cognitive interviews. A multicenter cross-sectional validation study was performed across eight ICUs at five hospitals in Japan. A total of 129 participants (103 nurses and 26 physicians) completed the Japanese CAFQa, the NIOSH Brief Job Stress Questionnaire, and the Insomnia Severity Index (ISI). Structural validity, internal consistency, test-retest reliability (n = 102), convergent validity, and known-groups validity were assessed. ResultsCFA confirmed the two-factor structure with acceptable fit (CFI = 0.922, RMSEA = 0.041, SRMR = 0.076), with standardized factor loadings ranging from 0.33 to 0.82. The two factors were not correlated (r = 0.05). Cronbachs alpha was 0.688 for the overall scale, 0.805 for Alarm Stress, and 0.649 for Alarm Coping. Test-retest ICCs ranged from 0.616 to 0.753. The CAFQa total score correlated with the NIOSH total (r = 0.261) and the ISI total (r = 0.338). Healthcare professionals with [≥]4 years of ICU experience had higher Alarm Coping scores than those with 1-3 years (median 7.0 vs 6.5), and physicians scored higher on Alarm Coping than nurses (median 8.0 vs 7.0). ConclusionsThe Japanese CAFQa demonstrated acceptable structural validity, reliability, and convergent and known-groups validity, providing the first validated tool for quantitatively measuring alarm fatigue in Japan. Implications for Clinical PracticeThe Japanese CAFQa enables ICU managers to quantify alarm fatigue at individual and unit levels, identify high-risk staff, and evaluate the effectiveness of alarm management interventions.

Waldenstrom macroglobulinemia (WM) is a rare indolent neoplasm characterized by presence of more than 10% lymphoid cells in BM that exhibit plasmacytoid or plasma cell differentiation that secretes an IgM monoclonal protein. This is a retrospective analysis of 89 patients of WM that describes the clinical and laboratory characteristics, treatment patterns and outcome of patients of WM. The median age of the entire cophort was 66 years with male predominance (67.4%). Most common presentations were symptoms pertaining to anemia (77.5%) and constitutional symptoms (33.7%). Median bone marrow lymphoplasmacytic cells were 41%. Positivity for MYD88 and CXCR4 mutations were seen in 81.8% and 2.4% cases. BR was the most common regimen used (52.8%). Overall response rates were seen at 87.8%. Median overall survival, progression free survival and time to next treatment is 8.49 years, 2.15 years and 3.88 years. BR regimen was associated with highest event free survival.

ObjectivesEpidural spinal cord stimulation (SCS) is an emerging therapy for motor rehabilitation following spinal cord injury (SCI) and other motor disorders. Conventionally, SCS leads are placed along the dorsal spinal cord (SCSD), where stimulation activates large diameter afferent fibers, which indirectly activate motoneurons through reflex pathways. This leads to broad activation of flexor and extensor muscles and limited fine-tuned control of motor output. Targeting the ventral spinal cord (SCSV) may enable more direct activation of motoneuron pools, potentially improving the specificity of muscle activation; however, there is currently no established method to place leads ventrally. To address this, we evaluated the feasibility of four modified percutaneous implantation techniques to target the ventrolateral thoracolumbar spinal cord. Materials and methodsPercutaneous SCSV implantation was performed in three human cadaver torso specimens under fluoroscopic guidance. The following approaches were evaluated: sacral hiatus, transforaminal, interlaminar contralateral, and interlaminar ipsilateral. The leads in the latter 3 approaches were inserted between L1 and L5. Eighteen implants were attempted, with nine leads retained for analysis. Lead and electrode position were assessed using computed tomography (CT) with three-dimensional reconstruction, along with anatomical dissection to verify lead and electrode placement within the epidural space. ResultsSuccessful ventral epidural lead placement was achieved using all four implantation approaches. The sacral hiatus (16/16 electrodes) and transforaminal (8/8 electrodes) approaches resulted in exclusively ventrolateral placement. The interlaminar contralateral approach led to 27/32 electrodes positioned ventrolaterally and 5/32 dorsally. The interlaminar ipsilateral implantation approach led to 14/32 electrodes positioned ventrolaterally and 18/32 positioned ventromedially. ConclusionsThese findings demonstrate that ventral epidural SCS lead placement can be achieved using modified percutaneous implant techniques. The four approaches outlined here provide a clinically feasible pathway to SCSV and establishes a foundation for future clinical studies investigating SCSV for motor rehabilitation following SCI.

Cancer-related casualties are the most common cause of death worldwide. The discovery of biomarkers is of utmost importance for diagnosis and disease monitoring. Herein, we performed a comprehensive metabolomics biomarker discovery effort in plasma from 615 lung, ovarian and colorectal cancer patients at diagnosis and 95 non-cancerous control subjects. This pan-cancer investigation identified specific panels of metabolites in the entire sample cohort with a high discriminating power and demonstrated by combined ROC AUC values of up to 0.95. The identified metabolites are mainly associated with lipid and amino acid metabolism as well as xenobiotic transformation. These metabolite panels of high predictive power provide new metabolic insights in these cancers and demonstrate the potential of metabolomics for improved diagnosis and monitoring disease progression.

Background: How post-COVID-19 condition (PCC) differs from post-acute infection syndromes (PAIS) caused by other respiratory viruses remains uncertain. Comparing these conditions may clarify whether post-acute symptoms reflect specific consequences of SARS-CoV-2 infection or broader post-viral mechanisms. Methods: We conducted a systematic review and meta-analysis of cohort studies comparing persistent symptoms or conditions in adults after SARS-CoV-2 infection with those following other acute respiratory viral infections. PubMed, Embase, and Scopus were searched. Random-effects models were used to estimate pooled risks. Results: Among 9,371 records screened, 22 studies were included and 14 contributed to the meta-analysis. Increased risk after SARS-CoV-2 infection was observed for pulmonary embolism, abnormal breathing, fatigue, hemorrhagic stroke, memory loss/brain fog, and palpitations; heart rate abnormalities showed borderline significance. For most other outcomes pooled estimates were inconclusive. Conclusions: Only a subset of outcomes appears more frequent after SARS-CoV-2 infection, suggesting many symptoms attributed to PCC may reflect broader post-viral syndromes.

Background: Potassium is involved in multiple physiological processes in the body, and hyperkalemia is a common, potentially life-threatening condition. Objective: The aim of our study was to examine the association between plasma potassium levels, and 30-day mortality in patients presenting to an emergency department with normo- or hyperkalemia. Design: Retrospective Cohort study. Setting: Emergency Departments in the Capital region of Denmark Participants: Persons attending Emergency Departments in the Capital Region of Denmark from 2017--2021 with a plasma potassium level of at least 3.5 mM measured within 4 hours after arrival. Measurements: The study was based on data from Danish National Registries and electronic patient records. We performed Kaplan-Meier survival analyses and unadjusted and adjusted cox regression analyses utilizing plasma [K+] 3.5--4.4 mM as the reference group for 30-day mortality hazard ratios (HRs). Results: A total of 248,453 patients were included with a median age of 60 years (Q1;Q3 42;75), and 6,959 (2.8%) died within 30 days. Mortality was 2.2% for potassium level 3.5--4.4 mM, 6.9% for 4.5--4.9 mM, 17.1% for 5.0--5.9 mM, and 26.9% for [≥] 6.0 mM. Unadjusted 30-day HRs were 3.2 (95%CI: 3.0--3.4) for [K+] 4.5--4.9 mM, 8.6 (95%CI: 7.9--9.3) for [K+] 5.0--5.9 mM, and 14.7 (95%CI: 12.5--17.0) for [K+] [≥]6.0 mM. Adjusted HRs were 1.4 (1.3--1.5), 2.10 (1.9--2.3), and 2.4 (2.0--2.8), respectively. Limitations: Risk of residual confounding. Missing data. No access to data regarding in-hospital treatment. Conclusion: Plasma potassium levels above 4.4 mM were associated with increased 30-day mortality among patients presenting to emergency departments. Primary funding source: Department of Emergency Medicine, Copenhagen University hospital, Bispebjerg and Frederiksberg Hospital.

Abstract Objective: The objective of this study was to compare hospital length of stay and other clinical outcomes between intact fish skin graft (IFSG; Graftguide, Kerecis, Arlington, VA) and synthetic/biosynthetic dermal substitutes (SSS; Integra Dermal Regeneration Template and NovoSorb Biodegradable Temporizing Matrix) in propensity score matched burn patients using the American Burn Association Burn Care Quality Platform. Methods: This retrospective cohort study identified adult patients treated with a single dermal substitute product during hospitalization for acute burn injury. Patients receiving IFSG (n = 93) were matched 1:4 to patients receiving SSS (n = 372) using nearest neighbor propensity score matching on the logit scale. Matching covariates included total body surface area burned (TBSA), patient age, sex), burn severity classification, inhalation injury, and trauma diagnosis. The primary outcome was hospital length of stay (LOS), analyzed using a gamma generalized linear mixed model (GLMM). Secondary outcomes included the incidences of sepsis, graft loss, venous thromboembolism (VTE), and hospital acquired pressure injury (HAPI). A prespecified sensitivity analysis was performed using a broader mixed product cohort. Results: A total of 93 IFSG treated patients from 17 burn centers admitted between the years 2019 and 2025 were matched 1:4 to 372 SSS treated patients from 44 centers. Unadjusted mean LOS was 24.1 days (median 20, IQR 11 to 32) in the IFSG treated group and 36.7 days (median 31, IQR 17 to 52) in the SSS treated group representing a 12.6 day reduction. GLMM-adjusted estimated marginal mean LOS was 24.2 days (95% CI, 20.0 to 29.4) for IFSG versus 33.5 days (95% CI, 30.0 to 37.6) for SSS (ratio 0.723; p = 0.00245), representing a 9.3 day reduction. Sepsis (1.1% vs 4.6%), graft loss (3.2% vs 8.3%), VTE (2.2% vs 2.7%), and HAPI (2.2% vs 3.8%) were all numerically lower in the IFSG treated arm; although GLMM-adjusted odds ratios were not statistically significant for any individual complication. The mixed cohort sensitivity analysis (n = 229 IFSG vs 458 SSS across 67 centers) confirmed the primary finding with GLMM adjusted LOS ratio 0.716 (p = 0.0001). Conclusions: In this propensity score matched analysis of the ABA registry, IFSG was associated with a statistically significant and clinically meaningful reduction in hospital length of stay compared with synthetic/biosynthetic dermal substitutes, in requiring dermal substitution and autografting, with all complication rates, sepsis, graft loss, VTE, and HAPI, numerically lower in the IFSG-treated arm. The shorter hospitalization was not achieved at the expense of safety. These findings support IFSG as a viable alternative to synthetic dermal substitutes in burns requiring dermal substitution and autografting. Prospective studies are warranted particularly in larger burns requiring staged reconstruction.

Background: Patient-ventilator synchrony, an essential prerequisite for non-invasive mechanical ventilation, requires an accurate matching of every phase of the respiration between patient and the ventilator. Methods: We developed a long short-term memory (LSTM)-based model that can predict the inspiratory and expiratory time of the patient. This model consisted of two hidden layers, each with eight LSTM units, and was trained using a dataset of approximately 27000 of 500-ms-long flow signals that captured both inspiratory and expiratory events. Results: The LSTM model achieved 97% accuracy and F1 score in the test data, and the average trigger error was less than 2.20%. In the first trial, 10 volunteers were enrolled. In "Compliance" mode, 78.6% of the triggering by the LSTM model was compatible with neuronal respiration, which was higher than Auto-Trak model (74.2%). Auto-Trak model performed marginally better in the modes of pressure support = 5 and 10 cmH2O. Considering the success in the first clinical trial, we further tested the models by including five patients with acute respiratory distress syndrome (ARDS). The LSTM model exhibited 60.6% of the triggering in the 33%-box, which is better than 49.0% of Auto-Trak model. And the PVI index of the LSTM model was significantly less than Auto-Trak model (36.5% vs 52.9%). Conclusions: Overall, the LSTM model performed comparable to, or even better than, Auto-Trak model in both latency and PVI index. While other mathematical models have been developed, our model was effectively embedded in the chip to control the triggering of ventilator. Trial registration: Approval Number: 2023ZDSYLL348-P01; Approval Date: 28/09/2023. Clinical Trial Registration Number: ChiCTR2500097446; Registration Date: 19/02/2025.

BackgroundPreterm birth is one of the most significant etiologies for neonatal morbidity and mortality. Preterm delivery is classified as iatrogenic preterm delivery and spontaneous preterm delivery. The role of placental pathology is studied. Materials and methodsWe have previously collected placental pathology data with maternal pregnancy and neonatal birth data, and we investigated the role of placental pathology in preterm delivery. Preterm delivery was categorized as late preterm (34-36 weeks), moderate preterm (32 to 33 weeks), and extreme preterm (less than 32 weeks). Neonatal, maternal, placental gross and histologic features, and laboratory parameters were compared across groups using chi-square tests for categorical variables and Kruskal-Wallis tests for continuous variables using various programs in R-package. ResultsTotally 3723 singleton placentas including 3307 term (88.8%) and 416 preterm placentas (11.2%) were examined with maternal pregnancy data and neonatal birth data. There were 614 placentas from patients with preeclampsia/pregnancy induced hypertension (PRE/PIH) (16.5%). Preterm delivery showed significantly lower fetal birth weight, placental weight, and fetal-placental ratio (all p<0.01). Maternal Black race was more prevalent in preterm groups (up to 50.8% in extreme preterm vs. 33.2% in term, p<0.01). Preterm delivery was statistically associated with PRE/PIH and maternal vascular malperfusion (MVM), maternal and fetal inflammatory response (MIR and FIR), and increased pre-delivery white blood count (WBC). Extreme preterm deliveries were markedly associated with intrauterine fetal death (27.5%, p<0.01) and MIR/FIR (56.7%, p<0.01). After excluding PRE/PIH patients, preterm delivery was statistically associated with MIR/FIR and increased WBC. ConclusionsDistinct clinicopathologic profiles exist across preterm subcategories, with MVM predominating in late/moderate preterm and severe pathologic features (including fetal demise and acute inflammation) in extreme preterm. These findings highlight heterogeneous etiologies of preterm delivery.

BackgroundIn long-term care facilities (LTCFs), close-contact identification often relies on staff recall and monitoring records because residents may be unable to self-report reliably. How these different record-generation processes relate to proximity-based sensor measurements in routine LTCF workflow remain unclear, and how such differences may influence contact-based decision-making in outbreak response is not well understood. MethodsWe conducted a five-day observational study in a Japanese LTCF using ultra-wideband (UWB) indoor positioning. Twenty-seven participants wore UWB tags, including 16 residents and 11 staff members; 10 staff members completed questionnaires. We compared UWB-derived proximity with questionnaire-derived contacts from staff self-report and monitoring-based proxy records, and assessed directional discrepancies under multiple distance-time thresholds. ResultsQuestionnaire-based records and UWB-derived proximity showed different patterns of discrepancy across contact types. Within this facility, resident-related monitoring-based proxy records showed relatively small directional discrepancies, whereas staff self-reports tended to identify additional resident-staff contacts under the baseline threshold ([&le;]1.0 m for [&ge;]15 min). Several alternative thresholds were associated with discrepancies closer to zero than the baseline, although the apparent ranking varied by summary metric. ConclusionsIn this single-facility observational study, different contact-list generation processes were associated with different patterns of discrepancy relative to a proximity-based operational measure. These findings support interpretation in terms of workflow-specific contact-list generation rather than a single universally optimal threshold and may help inform facility-level review of contact identification practices in LTCFs. These findings support aligning contact identification strategies with facility-specific workflows to improve the feasibility and effectiveness of IPC practices in LTCFs.

Aims: Responses to remote pulmonary artery pressure data vary across programs. We evaluated SMART-HF, a structured pulmonary artery diastolic pressure (PAD)-guided workflow, in a community heart failure cohort. Methods: We retrospectively analysed adults with heart failure and an implanted pulmonary artery pressure sensor managed with SMART-HF. Pulmonary artery diastolic pressure (PAD) was calculated from prespecified 14-day windows at baseline, 90 days, and 6 months. Two hemodynamic management performance indices (HMPI) were prespecified: the 6-Month Delta HMPI (PAD reduction >2 mmHg from baseline) and the 90-Day Target HMPI (PAD [&le;]20 mmHg at 90 days). Exploratory analyses evaluated patients with baseline PAD >20 mmHg. Results: Of 37 patients, 36 had paired 90-day and 29 had paired 6-month windows. Mean PAD decreased from 18.3 +/- 7.0 to 16.1 +/- 6.3 mmHg at 90 days and from 18.8 +/- 6.8 to 15.5 +/- 5.8 mmHg at 6 months (both P < 0.001). The 90-Day Target HMPI was achieved in 26/36 (72.2%) and the 6-Month Delta HMPI in 19/29 (65.5%) [95% CI 45.7-82.1]. In the exploratory subgroup (baseline PAD >20 mmHg), mean PAD changes were -2.9 +/- 3.6 mmHg at 90 days (n = 19; P = 0.002) and -4.9 +/- 4.9 mmHg at 6 months (n = 15; P = 0.002). Conclusions: SMART-HF was associated with improved ambulatory pulmonary artery diastolic pressure control at 90 days and 6 months. Exploratory subgroup findings support further evaluation in patients with elevated baseline pulmonary artery diastolic pressure.

BackgroundThe COVID-19 pandemic exposed critical shortages of mechanical ventilators, particularly in low-resource settings. Disruptions in global supply chains and dependence on specialized components highlighted the need for scalable, locally manufacturing alternatives for emergency respiratory support. AimTo describe and evaluate a simplified, supply-chain-independent mechanical ventilator assembled from widely available automotive and simple hardware components, and intended as a last-resort solution. MethodsThe ventilator is based on a reciprocating air pump driven by an automotive windshield wiper motor coupled to parallel shaft bellows and readily assembled passive membrane valves, only requiring materials available from standard hardware retailers, minimal tools, and basic manual skills. Ventilator performance was assessed through bench testing using a patient model simulating severe lung disease in an adult (R=20 cmH2O{middle dot}s/L, C=15 mL/cmH2O) and pediatric (R=50 cmH2O{middle dot}s/L, C=10 mL/cmH2O) patients. Realistic proof of concept was performed in four mechanically ventilated 50-kg pigs. ResultsThe device delivered tidal volumes up to 600 mL and respiratory rates up to 45 breaths/min with PEEP up to 10 cmH2O, covering pediatric and adult ventilation ranges. In vivo testing showed that the ventilator maintained arterial blood gases within the targeted range. Technical details for ventilator construction are provided in an open-source video tutorial. DiscussionThis low-cost ventilator demonstrated adequate performance under demanding conditions. Although not a substitute for commercial intensive care ventilators, its simplicity, autonomy, and independence from fragile supply chains provide a potentially life-saving option in resource-constrained emergency scenarios.

Background. Pancreatic ductal adenocarcinoma (PDAC) has a five-year survival rate of approximately 12%, largely because it is typically diagnosed at an advanced stage. CT-based computational methods for early detection exist but rely on black-box deep learning or large texture feature sets without tissue-specific interpretability. Methods. We developed Virtual Spectral Decomposition (VSD), which applies six parameterized sigmoid functions S(HU) = 1/(1+exp(-alpha x (HU - mu))) to standard portal-venous CT, decomposing each pixel into tissue-specific response channels for fat (mu=-60), fluid (mu=10), parenchyma (mu=45), stroma (mu=75), vascular (mu=130), and calcification (mu=250). Dendritic Binary Gating identifies structural content per channel using morphological filtering, enabling co-firing analysis and lone firer identification. A 25-feature signature was extracted per patient. Three independent datasets were analyzed: NIH Pancreas-CT (n=78 healthy), Medical Segmentation Decathlon Task07 (n=281 PDAC, paired tumor/adjacent tissue), and CPTAC-PDA from The Cancer Imaging Archive (n=82, multi-institutional, with DICOM time point tags). The same six sigmoid parameters were used across all datasets without retraining. Results. VSD achieved AUC 0.943 for field effect detection (healthy vs cancer-adjacent parenchyma) and AUC 0.931 for patient-stratified tumor specification on MSD. On CPTAC-PDA, VSD achieved AUC 0.961 (6 features) and 0.979 (25 features) for distinguishing healthy from cancer-bearing pancreas on scans obtained prior to pathological diagnosis. All significant features replicated across datasets in the same direction: z_fat (d=-2.10, p=3.5e-27), z_fluid (d=-2.76, p=2.4e-38), fire_fat (d=+2.18, p=1.2e-28). Critically, VSD severity did not correlate with days-from-diagnosis (r=-0.008, p=0.944) across a range of day -1394 to day +249. Patient C3N-01375, scanned 3.8 years before pathological diagnosis, had VSD severity 1.87, well above the healthy mean of 0.94 +/- 0.33. The tissue transformation signature was temporally stable, indicating an early, persistent tissue state rather than a progressively worsening process. Conclusions. VSD with Dendritic Binary Gating detects a stable pancreatic tissue composition signature on standard CT that is present years before clinical diagnosis, validated across three independent datasets without parameter adjustment. The six sigmoid channels map to biologically meaningful tissue components through a fully transparent interpretability chain. The temporal stability of the signal implies a detection window of 3-7 years, consistent with known PanIN-3 microenvironment transformation timelines. VSD functions as a single-scan screening tool applicable to any abdominal CT performed during the pre-clinical window.

AimWe examined associations between smoking and HbA1c among U.S. adults, and whether these associations vary by diabetes status. MethodsWe analyzed NHANES data from 2015-2018 for adults aged [&ge;]20 years. Smoking was assessed by self-report and serum cotinine. Survey-weighted multivariable linear regression was used to evaluate the association between smoking and HbA1c in the full population (N=9,214) and in adults without diabetes (N=7,328), adjusting for demographics, blood pressure, waist circumference, lipids, and C-reactive protein. ResultsAfter adjustment for cardiometabolic covariates, there was no significant association between smoking and HbA1c in the full population (former: {beta}=0.029%, p=0.30; current: {beta}=0.053%, p=0.13). Among adults without diabetes, former smoking was not associated with HbA1c, whereas current smoking remained significantly associated (former: {beta}=-0.001%, p=0.923; current: {beta}=0.067%, p<0.001). These findings were similar when cotinine was used as the exposure measure, with active smoking ([&ge;]3.0 ng/mL) associated with higher HbA1c among non-diabetic adults (p<0.001), but not in the full population. ConclusionsAmong adults without diabetes, current but not former smoking was associated with higher HbA1c. The absence of an association in former smokers suggests that this effect may attenuate following cessation. These findings support early cessation interventions and may inform cessation counseling and diabetes screening.

ObjectivesWe determined the frequency of sexually transmitted infection (STI) testing among people accessing sexual health services (SHS) in England. MethodsWe assessed STI testing frequency in face-to-face and online SHSs in England using data from the GUMCAD STI surveillance system. We quantified different combinations of tests (e.g. single chlamydia test or full STI screen), number of tests completed in 2024 and test positivity by sociodemographic and behavioural characteristics, as well as clinical setting and outcomes. ResultsOverall, there were 2,222,028 attendances at SHS in England in 2024 that involved tests for chlamydia, gonorrhoea, syphilis and/or HIV. Most of these attendances involved tests for all four of these STIs. Most people accessing SHS in England tested once (80.1%), and a small minority (1.9%) tested at least quarterly (4+ times). Some groups had a comparably larger proportion of quarterly testers; these included gay, bisexual, and other men who have sex with men (GBMSM) (6.7%), London residents (3.6%), online testers (2.5%), people using HIV-PrEP (13%), and people with 5+ partners in the previous 3 months (10.6%). Only 10.5% of GBMSM reporting higher-risk sexual behaviours tested quarterly despite recommendations for quarterly testing in this group. ConclusionsThe majority of those who tested for STIs in England in 2024 only tested once. The minority who tested at least quarterly had a higher proportion of GBMSM, people using HIV-PrEP, London residents and people reporting higher risk behaviours. Quarterly testing often appears to be aligned with current testing recommendations in England; however, we also observed that only a low proportion of behaviourally high-risk GBMSM and HIV-PrEP users are meeting these recommendations. It is important to acknowledge groups with lower or higher testing frequency when developing interventions and updating guidelines related to STI testing. WHAT IS ALREADY KNOWN ON THIS TOPICThe effectiveness of asymptomatic testing for chlamydia and gonorrhoea in gay, bisexual and other men who have sex with men (GBMSM), and the potential impact of the consequent increased antibiotic use on rising antimicrobial resistance and individual harm has recently been questioned. Testing and treatment remains a key pillar of STI prevention and management; despite this, there is limited evidence of STI testing frequency within sexual services (SHS) on a national level. WHAT THIS STUDY ADDSThis analysis shows that the majority of people attending SHSs in England in 2024 tested once, and only a small proportion of behaviourally high-risk people tested frequently. HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICYAwareness of groups that are behaviourally high risk but testing infrequently is important to guide interventions and messaging regarding STI testing. The low levels of frequent testing, even among those who would be recommended quarterly testing under UK guidelines, provides important context for wider discussion around asymptomatic STI screening.