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Background Creutzfeldt-Jakob disease (CJD) is a rapidly progressive and ultimately fatal neurodegenerative condition caused by prions. The clinical symptoms of CJD vary with its subtype, and may include dementia, visual hallucinations, myoclonus, ataxia, (extra)pyramidal signs and akinetic mutism. In the early course of disease however, several clinical symptoms of CJD may mimic those of co-existing morbidities. Case presentation We report a male in his 60s with a history of situs inversus totalis and Churg Strauss syndrome, who presented with speech fluency disturbances, neuropsychiatric symptoms and allodynia, a few months after becoming a widower. Initially presumed a bereavement disorder along with a flare-up of Churg Strauss, his symptoms gradually worsened with apraxia, myoclonic jerks and eventually, akinetic mutism. MRI revealed hyperintensities at the caudate nucleus and thalami, while the cerebrospinal fluid was positive for the 14-3-3 protein and the real-time quick test, making the diagnosis of CJD highly probable. This case illustrates the complexities that may arise in diagnosing CJD when pre-existing multimorbidity may cloud the clinical presentation. We also discuss the potential mechanisms underlying the co-occurrence of three rare conditions (situs inversus totalis, Churg Strauss syndrome, CJD) in one patient, taking into consideration the possibility of coincidence as well as common underlying factors. Conclusions The diagnosis of CJD may be easily missed when its clinical symptoms are obscured by those of pre-existing (rare) multimorbidity. This case highlights that when the multimorbidity has neurological manifestations, an extensive evaluation remains crucial to establish the diagnosis, minimize the risk of prion-transmission and provide appropriate guidance to patients and their caregivers.

The United States government spends over $85 billion annually on treating non-dialysis chronic kidney disease (CKD). Patients with CKD are prescribed a multitude of medications to manage numerous comorbidities associated with CKD. Thus, this study aims to investigate the association between polypharmacy and health-related quality of life (HRQoL) in non-dialysis CKD patients. This cross-sectional study utilized data from the Medical Expenditure Panel Survey (MEPS) from 2010 through 2019. We classified polypharmacy into three groups based on the number of medication classes: [less than or equal to] 4 (minor polypharmacy), 5 through 9 (major polypharmacy), and [greater than or equal to] 10 (hyperpolypharmacy). To measure HRQoL, a Physical Component Summary (PCS) and a Mental Component Summary (MCS) were obtained from the 12-item Short-Form Health Survey version 2 and Veteran's Rand 12 item. We applied multivariable ordinary least squares regression to assess the association between polypharmacy and HRQoL in non-dialysis CKD patients. A total of 649 CKD patients (weighted n = 667,989) were included. Patients with minor polypharmacy, major polypharmacy, and hyperpolypharmacy were 22.27%, 48.24%, and 29.48%, respectively. Major polypharmacy and hyperpolypharmacy were significantly and negatively associated with lower PCS scores when compared with minor polypharmacy [Beta = -3.12 (95% CI: -3.62, -2.62), p-value<0.001; Beta = -4.13 (95CI: -4.74, -3.52), p-value<0.001]. Similarly, major polypharmacy and hyperpolypharmacy were significantly and negatively associated with lower MCS scores when compared to minor polypharmacy [Beta = -0.38 (95% CI: -0.55, -0.20), p-value<0.001; Beta = -1.70 (95% CI: -2.01, -1.40), p-value<0.001]. The top 5 classes of medications used by CKD patients were antihyperlipidemic (56.31%), beta-adrenergic blockers (49.71%), antidiabetics (42.14%), analgesics (42.17%), and diuretics (39.65%). Our study found that both major polypharmacy and hyperpolypharmacy were associated with lower HRQoL among non-dialysis CKD patients. This study highlights the need for further evaluation of the combination of medications taken by non-dialysis CKD patients to minimize unnecessary and inappropriate medication use.

This paper introduces the Adaptive Hierarchical Multi-Objective Resource Optimizer (AH-MORO), a ground-breaking framework for subcarrier allocation in Smart Grid Neighborhood Area Networks (NANs), addressing critical limitations of existing methods in dynamic, high-density environments. Traditional approaches suffer from static resource allocation, inefficient interference management, and poor scalability, leading to suboptimal throughput, latency, and energy consumption. AH-MORO innovates through three core mechanisms: (1) a hierarchical multi-objective optimization model that dynamically balances throughput maximization, latency minimization, and energy efficiency using adaptive weight parameters (λ₁, λ₂, λ₃), (2) a dual-layered interference mitigation system combining constraint-based subcarrier assignment and adaptive power control to suppress co-channel interference, and (3) a metaheuristic solver (Genetic Algorithm-Deep Reinforcement Learning hybrid) enabling real-time, low-complexity optimization under fluctuating traffic loads. Rigorous simulations demonstrate AH-MORO’s superiority over state-of-the-art methods, achieving 37.5% higher throughput, 34.2% lower latency, 24% reduced energy consumption, and 33.3% improved interference reduction in dense urban NANs (1,000 + devices). The framework uniquely guarantees QoS via fairness constraints, ensuring minimum throughput ( T min ) ) for all users while adhering to strict latency ( L max and energy ( E max ) bounds. These results validate AH-MORO as the first holistic solution for real-time, energy-efficient, and interference-resilient Smart Grid communications, setting a new benchmark for adaptive resource management in next-generation NANs.

NbSe 2 is a transition metal dichalcogenide with a two-dimensional nature, showing superconducting (SC) and charge density properties. Moreover, a 1T phase can be made in the film, which has a different property from the bulk dominant 2 H phase, in which Mott insulator behavior is actively discussed. We observed the surface with STM at 400 mK and injected RF signal (1 GHz and 15 Hz) at the tunneling junction. We detected two quasi-particle (QP) states at the end of the SC gap, which split with the increase of the RF power specified by the electric field at the tunneling junction, V AC . A previous STM experiment with 65 GHz RF on a vanadium surface observed multiple replicas of the QP peak. However, our experimental result using 1 GHz RF shows a widening of QP features with two enhanced peaks shifted by ~ ± eV AC from the original QP positions. The behavior was well reproduced by a simulation using a well-known Tien-Gordon model, whose results indicate that the disappearance of multiple peaks is due to the low frequency of the RF signal. In addition, two enhanced peaks at ~ ± eV AC are deduced from the Bessel function behavior. The energy shift from the original peak linearly changes with eV AC . We apply this technique to examine the property change at the domain boundary of the 2 H and 1T phase of the NbSe 2 surface. We found the superconducting gap decreases when we move the tip from the 2 H domain into the 1T domain. Moreover, the injection of RF splits a QP peak into two enhanced peaks, whose energy separation is linear with the electric field at the RF generator for both phases. However, the linear energy separation with V AC shows different coefficients between the 2 H and 1T phases. We conclude that the different coefficient is due to the change of actual V Ac on the two domains originating from a different dielectric constant and shielding efficiency for the electric field of RF.

Early-life environmental factors have been suggested in the pathophysiology of dementia. Season of birth has previously been used as a proxy for these external exposures. We investigated the link between season of birth and the risk of dementia and further explored underlying pathways by studying structural brain changes on MRI. From the Dutch, population-based Rotterdam Study, 12,964 participants born between 1887 and 1960 were followed between 1990 and 2018 for dementia. Cox regression was conducted to assess the association between season of birth and dementia. In addition, we distinguished between mild and cold winters. The association of season of birth with structural brain markers on MRI was examined in 5237 participants. The risk of dementia in participants born in winter and fall was higher than of those born in summer (hazard ratio (HR) 1.15 [95% confidence interval (CI) 1.01–1.31] for winter and HR 1.17 [95% CI 1.01–1.33] for fall), especially for Alzheimer’s disease (HR 1.23 [1.06–1.43] for winter and HR 1.15 [95% CI 0.99–1.35] for fall). The risk was particularly increased for participants born in a cold winter. Except for slightly lower hippocampus in fall born participants (β − 0.03; 95% CI − 0.06 to 0.00), we did not find associations with brain imaging markers. In conclusion, winter and fall births were associated with a higher incidence of dementia, especially of AD. We did not find evidence for structural brain changes as an underlying mechanism.

Risk stratification is critical for the early identification of high-risk individuals and disease prevention. Here we explored the potential of nuclear magnetic resonance (NMR) spectroscopy-derived metabolomic profiles to inform on multidisease risk beyond conventional clinical predictors for the onset of 24 common conditions, including metabolic, vascular, respiratory, musculoskeletal and neurological diseases and cancers. Specifically, we trained a neural network to learn disease-specific metabolomic states from 168 circulating metabolic markers measured in 117,981 participants with ~1.4 million person-years of follow-up from the UK Biobank and validated the model in four independent cohorts. We found metabolomic states to be associated with incident event rates in all the investigated conditions, except breast cancer. For 10-year outcome prediction for 15 endpoints, with and without established metabolic contribution, a combination of age and sex and the metabolomic state equaled or outperformed established predictors. Moreover, metabolomic state added predictive information over comprehensive clinical variables for eight common diseases, including type 2 diabetes, dementia and heart failure. Decision curve analyses showed that predictive improvements translated into clinical utility for a wide range of potential decision thresholds. Taken together, our study demonstrates both the potential and limitations of NMR-derived metabolomic profiles as a multidisease assay to inform on the risk of many common diseases simultaneously. In a study involving more than 100,000 individuals in the UK Biobank, a neural network model trained on metabolomic data can predict disease risk for over 20 conditions and adds predictive information over clinical variables for eight common diseases.

Cardiovascular disease (CVD) is the leading cause of death in women worldwide. The cardiovascular risk profile deteriorates after women enter menopause. By definition, women diagnosed with premature ovarian insufficiency (POI) experience menopause before 40 years of age, which may render these women even more susceptible to develop CVD later in life. However, prospective long-term follow up data of well phenotyped women with POI are scarce. In the current study we compare the CVD profile and risk of middle aged women previously diagnosed with POI, to a population based reference group matched for age and BMI. We compared 123 women (age 49.0 (± 4.3) years) and diagnosed with POI 8.1 (IQR: 6.8-9.6) years earlier, with 123 population controls (age 49.4 (± 3.9) years). All women underwent an extensive standardized cardiovascular screening. We assessed CVD risk factors including waist circumference, BMI, blood pressure, lipid profile, pulse wave velocity (PWV), and the prevalence of diabetes mellitus, metabolic syndrome (MetS) and carotid intima media thickness (cIMT), in both women with POI and controls. We calculated the 10-year CVD Framingham Risk Score (FRS) and the American Heart Association's suggested cardiovascular health score (CHS). Waist circumference (90.0 (IQR: 83.0-98.0) versus 80.7 (IQR: 75.1-86.8), p < 0.01), waist-to-hip ratio (0.90 (IQR: 0.85-0.93) versus 0.79 (IQR: 0.75-0.83), p < 0.01), systolic blood pressure (124 (IQR 112-135) versus 120 (IQR109-131), p < 0.04) and diastolic blood pressure (81 (IQR: 76-89) versus 78 (IQR: 71-86), p < 0.01), prevalence of hypertension (45 (37%) versus 21 (17%), p < 0.01) and MetS (19 (16%) versus 4 (3%), p < 0.01) were all significantly increased in women with POI compared to healthy controls. Other risk factors, however, such as lipids, glucose levels and prevalence of diabetes were similar comparing women with POI versus controls. The arterial stiffness assessed by PWV was also similar in both populations (8.1 (IQR: 7.1-9.4) versus 7.9 (IQR: 7.1-8.4), p = 0.21). In addition, cIMT was lower in women with POI compared to controls (550 μm (500-615) versus 684 μm (618-737), p < 0.01). The calculated 10-year CVD risk was 5.9% (IQR: 3.7-10.6) versus 6.0% (IQR: 3.9-9.0) (p = 0.31) and current CHS was 6.1 (1.9) versus 6.5 (1.6) (p = 0.07), respectively in POI versus controls. Middle age women with POI presented with more unfavorable cardiovascular risk factors (increased waist circumference and a higher prevalence of hypertension and MetS) compared to age and BMI matched population controls. In contrast, the current study reveals a lower cIMT and similar 10-year cardiovascular disease risk and cardiovascular health score. In summary, neither signs of premature atherosclerosis nor a worse cardiovascular disease risk or health score were observed among middle age women with POI compared to population controls. Longer-term follow-up studies of women of more advanced age are warranted to establish whether women with POI are truly at increased risk of developing CVD events later in life. ClinicalTrials.gov Identifier: NCT02616510.

Background: Pain is a prevalent issue among breast cancer patients and survivors, with a significant proportion receiving hydrocodone for pain management. However, the rescheduling of hydrocodone from Schedule III to Schedule II by the U.S. Drug Enforcement Administration (DEA) in October 2014 raised concerns about potential barriers to opioid access for cancer patients, particularly among vulnerable populations such as dually eligible Medicare–Medicaid beneficiaries and racial/ethnic minorities. Methods: We conducted a retrospective cohort study using Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data including 52,306 early-stage breast cancer patients from 2011 to 2019. We employed multivariable logistic regression models with model specification tests to stratify the subgroups and evaluate the differential effects of the policy change by Medicaid dual eligibility and race–ethnicity, while adjusting for other patient demographics, clinical characteristics, and cancer treatments. Results: The rescheduling of hydrocodone was associated with significantly different effects on prescription opioid use across subgroups, with the most pronounced reduction in hydrocodone prescription observed among dual-eligible racial/ethnic minority patients (adjusted odds ratio [AOR] = 0.57; 95% confidence interval [CI]: 0.44–0.74; p < 0.001). Non-dual-eligible patients experienced a smaller reduction in hydrocodone use (AOR = 0.84; 95% CI: 0.78–0.90; p < 0.001). Concurrently, non-hydrocodone opioid use significantly increased among non-dual-eligible non-Hispanic White patients (AOR = 1.29; 95% CI: 1.19–1.40; p < 0.001), suggesting a substitution effect, while smaller non-significant increases were observed among other subgroups. Conclusions: Hydrocodone rescheduling led to the greatest reduction in hydrocodone use among dual-eligible racial–ethnic minority patients. The corresponding increase in non-hydrocodone opioid use was limited to non-dual-eligible non-Hispanic White patients. These findings highlight the need for opioid policies that balance misuse prevention with equitable access to pain relief, particularly among underserved populations.

Chilli, a globally cultivated and consumed crop is significantly impacted by Thrips parvispinus. The reliance on pesticides could result in residue contamination, adversely affecting quality, leading to export rejections and health risks to consumers. This study evaluated the bioefficacy and persistent toxicity of fipronil and tolfenpyrad against thrips in chilli, and persistence of their residues. Tolfenpyrad demonstrated higher field efficacy (60.94 to 78.53%) against thrips compared to fipronil (37.61 to 58.07%). Residue analysis was performed in leaves and green chilli fruits using LC–MS/MS. Fipronil’s efficacy decreased after 5 to 7 days of application, but both fipronil and tolfenpyrad residues remained for 20 and 30 days, respectively. In contrast, the residues in leaves caused persistent toxicity to thrips, causing about 50% mortality until 10 to 15 days in tolfenpyrad treatment. In green chilli, residues of tolfenpyrad and fipronil persisted for up to 40 and 25 days, necessitating pre-harvest intervals of 3.17 and 19.39 to 30.65 days, respectively, but with no dietary risk to consumers. Tolfenpyrad exhibited superior efficacy against T. parvispinus compared to fipronil, with a longer duration of effectiveness in leaves and quicker residue dissipation in chilli fruits and a short pre-harvest interval, supporting its use in Integrated Pest Management.

Evidence for associations between long-term protein intake with mortality is not consistent. We aimed to examine associations of dietary protein from different sources with all-cause and cause-specific mortality. We followed 7786 participants from three sub-cohorts of the Rotterdam Study, a population-based cohort in the Netherlands. Dietary data were collected using food-frequency questionnaires at baseline (1989–1993, 2000–2001, 2006–2008). Deaths were followed until 2018. Associations were examined using Cox regression. Additionally, we performed a highest versus lowest meta-analysis and a dose–response meta-analysis to summarize results from the Rotterdam Study and previous prospective cohorts. During a median follow-up of 13.0 years, 3589 deaths were documented in the Rotterdam Study. In this cohort, after multivariable adjustment, higher total protein intake was associated with higher all-cause mortality [e.g. highest versus lowest quartile of total protein intake as percentage of energy (Q4 versus Q1), HR = 1.12 (1.01, 1.25)]; mainly explained by higher animal protein intake and CVD mortality [Q4 versus Q1, CVD mortality: 1.28 (1.03, 1.60)]. The association of animal protein intake and CVD was mainly contributed to by protein from meat and dairy. Total plant protein intake was not associated with all-cause or cause-specific mortality, mainly explained by null associations for protein from grains and potatoes; but higher intake of protein from legumes, nuts, vegetables, and fruits was associated with lower risk of all-cause and cause-specific mortality. Findings for total and animal protein intake were corroborated in a meta-analysis of eleven prospective cohort studies including the Rotterdam Study (total 64,306 deaths among 350,452 participants): higher total protein intake was associated with higher all-cause mortality [pooled RR for highest versus lowest quantile 1.05 (1.01, 1.10)]; and for dose–response per 5 energy percent (E%) increment, 1.02 (1.004, 1.04); again mainly driven by an association between animal protein and CVD mortality [highest versus lowest, 1.09 (1.01, 1.18); per 5 E% increment, 1.05 (1.02, 1.09)]. Furthermore, in the meta-analysis a higher plant protein intake was associated with lower all-cause and CVD mortality [e.g. for all-cause mortality, highest versus lowest, 0.93 (0.87, 0.99); per 5 E% increment, 0.87 (0.78, 0.98), for CVD mortality, highest versus lowest 0.86 (0.73, 1.00)]. Evidence from prospective cohort studies to date suggests that total protein intake is positively associated with all-cause mortality, mainly driven by a harmful association of animal protein with CVD mortality. Plant protein intake is inversely associated with all-cause and CVD mortality. Our findings support current dietary recommendations to increase intake of plant protein in place of animal protein. Clinical trial registry number and website NTR6831, https://www.trialregister.nl/trial/6645