The computational design of molecular quantum devices requires methods that capture "the quantum and the chemistry," approaching chemical accuracy for large numbers of entangled and/or strongly correlated electrons. Projected-interacting full configuration interaction (PiFCI) is a candidate for such simulations, providing a formally exact and systematically improvable approximation for correlation in large active spaces. PiFCI extends Kohn-Sham density functional theory by introducing multiple reference systems, each experiencing an electron-electron interaction projected onto one or more one-electron states. Compact CI expansions yield near-exact reference system wavefunctions, and projected exchange-correlation (XC) density functionals enable formally exact combinations of reference system correlation energies. This work presents a general treatment of the projected interactions in PiFCI and introduces regularized second-order many-body perturbation theory (MP2) as an approximate projected XC functional. Numerical results show that PiFCI plus regularized MP2 can accurately treat dynamical and nondynamical correlation in relatively large active spaces, including stacks of entangled singlet-coupled tetrathiafulvalene and phenalenyl organic radicals modeling molecular quantum devices.
Regular follow-up visits are essential for effective management and prevention of complications of chronic diseases like hypertension (HT), diabetes mellitus (DM), cardiovascular disease (CVD), and coronary artery disease (CAD), and many more, for continuity of care and improved patient outcomes including quality of life. However, consultation fees act as a significant barrier, particularly in low- and middle-income populations, where out-of-pocket expenses deter patients from adhering to follow-up schedules. This article explores how consultation fees influence patient behavior, reduce compliance with medical advice, and ultimately compromise the quality of care and life. A review of current literature highlights the financial challenges faced by patients and allows us to think about potential policy solutions, including subsidized follow-ups, bundled care models, and extended free follow-up windows. Addressing this financial constraint is critical for ensuring equitable access to ongoing care and improving long-term health outcomes. Well-planned research on this issue is required for long-term planning.
This paper constructed a reactive oxygen species(ROS)-responsive hydrogel loaded with sodium tanshinone Ⅱ_A sulfonate(STS) and salvianolic acid B(SAB) and evaluated its therapeutic effect on hypertrophic scars. A hydrogel was prepared by using hyaluronic acid(HA) and polyvinyl alcohol(PVA) bridged by phenylboronic acid(PBA) as the matrix with two drugs physically encapsulated inside. Its structure, rheological properties, and drug release behavior were characterized. Scar models of rabbit ears were established and divided into a blank control group, a model group, an asiaticoside cream group, a regular drug-loaded hydrogel group, and a drug-loaded ROS-responsive hydrogel group. After 21 days of intervention, the net increased thickness of the car was detected. The tissue morphology was detected by using hematoxylin-eosin and Masson staining. The expressions of α-smooth muscle actin(α-SMA) and collagen-Ⅰ(COL-Ⅰ) were detected by immunohistochemistry, and the levels of transforming growth factor-β1(TGF-β1), tissue inhibitor of metalloproteinases-1(TIMP-1), matrix metallopeptidase-9(MMP-9), ROS, and 8-hydroxy-2'-deoxyguanosine(8-OHdG) were assessed. The results show that, compared to those in the model group, the net increased thickness of scar, TGF-β1, TIMP-1, ROS, 8-OHdG, α-SMA, and COL-Ⅰ in each treatment group were significantly reduced(P<0.05), while MMP-9 levels were increased(P<0.05), and the improvement effect in the drug-loaded ROS-responsive hydrogel group was better than that in the regular drug-loaded hydrogel group(P<0.05). These findings indicate that the hydrogel can achieve smart drug release and significantly inhibit scar formation, providing a new strategy for treatment.
Previous research has shown that people are sensitive to statistical regularities and will implicitly learn to bias attention toward locations and features frequently associated with search targets. However, most prior work has involved a single biasing contingency. In Experiment 1, we investigate whether individuals can simultaneously learn and implement two distinct contingencies: one based on location and another based on color. The results suggest that both contingencies are learned implicitly and exert independent effects on attentional allocation. Experiments 2 and 3 examine whether shifting one feature to the volitional system via endogenous cues affects the implicit learning and implementation of contingencies for the other feature. The findings indicate that endogenous cues for one feature do not block implicit learning of contingencies in the other. However, the influence of implicit contingencies on attentional allocation depends on the validity of the volitional cues: they are effective when cues are neutral or valid, but not when invalid. This pattern suggests that the implicit and volitional systems operate hierarchically, with the volitional system taking precedence. SIGNIFICANCE STATEMENT: Efficient attentional guidance is key to effective visual search. While both volitional control and statistical learning can guide attention, little is known about how attention is influenced when multiple guidance mechanisms compete. Using a task with competing statistical regularities, one for target location and one for color, we show that both statistical learning biases independently influence attention. Shifting a feature to the volitional control system does not disrupt the statistical learning of the other, but invalid volitional cues eliminate statistical learning effects, suggesting a hierarchical relationship. These findings offer new insight into how multiple guidance systems shape attentional allocation. OPEN PRACTICES STATEMENT: Subject level data and SPSS analysis syntax available on the Open Science Framework at: https://osf.io/5vt74/overview . The experiments were not preregistered, but the data, and analysis syntax are publicly available at https://osf.io/5vt74/overview .
BackgroundHistorically, OFF burden in Parkinson's disease has been primarily attributed to motor features. Recent studies highlight that non-motor symptoms, and the predictability of OFF episodes also drive functional impairment, yet they are rarely measured in clinical practice.ObjectiveTo identify which clinical features are most closely associated with OFF time and OFF impact, and to quantify the added explanatory value of temporal predictability, non-motor, and behavioural domains beyond a core motor model.MethodsWe analysed 1252 OFF-only visits from 430 PPMI participants. Outcomes were MDS-UPDRS IV 4.3 (OFF time) and 4.4 (OFF impact). Linear mixed-effects models with a participant random intercept were fitted. The core motor model included OFF-state motor severity, freezing, tremor, levodopa responsiveness, and dyskinesia, plus covariates. Predictability (IV 4.5), non-motor (mood, fatigue/sleep, autonomic/GI), and behavioural (impulse-control behaviours) domains were then added to assess added influence beyond motor. Analyses were stratified by time since diagnosis (Pooled; ≤ 4 y; ≥ 6 y).ResultsClinical features explained more variance in OFF impact than OFF time (25.9% vs 8.1%). OFF time was primarily linked to OFF-state motor severity/freezing, with levodopa responsiveness important early. For OFF impact, predictability produced the largest increment in marginal R2 beyond the core motor model (pooled and Late). Within the core motor model, tremor was the largest contributor to OFF impact.ConclusionsPredictability is a prominent correlate of OFF impact. Asking about predictability may help tailor therapy, from timing optimisation to on-demand rescue for unpredictable episodes. Understanding OFF Periods in Parkinson's Disease: Why Predictability Matters for Daily Life and Treatment ChoicesPeople with Parkinson's disease often experience “OFF periods,” when their usual medication stops working and symptoms return. These episodes can make everyday activities difficult. Traditionally, OFF periods have been measured by how much time they last, but patients often say that unpredictability, when OFF episodes happen without warning, is even more disruptive.Our study looked at data from over 1200 clinic visits in a large international research project. We examined two aspects of OFF burden: OFF time – how much of the day is spent in an OFF state.OFF impact – how much OFF episodes interfere with daily life.We correlated these with motor symptoms (such as tremor and freezing), non-motor symptoms (such as anxiety and fatigue), and a measure of predictability (how regular or irregular OFF episodes are).We found that OFF impact was strongly linked to predictability. However, this does not mean unpredictability alone makes OFF worse, it may reflect a different type of OFF episode. Predictable “wearing-off” usually occurs gradually as medication wears off, while “on–off fluctuations” can happen suddenly and are often more severe. Our findings suggest that patients who experience these abrupt changes report greater disruption to daily life.Why does this matter? Asking patients whether they can predict their OFF episodes may help doctors choose the right treatment. Predictable wearing-off can often be managed by adjusting medication timing or adding long-acting drugs. On–off fluctuations may need fast-acting rescue treatments. In some cases, frequent unpredictable OFF episodes may signal the need to consider advanced options like infusion therapies or deep brain stimulation earlier in care.Our findings suggest that predictability should be part of routine assessment, alongside motor symptoms. Future research should explore whether improving predictability or targeting these more severe fluctuations can reduce the impact of OFF periods.
Left-behind children (LBC) in rural China often have limited opportunities for regular physical activity and may face heightened psychological difficulties. School physical education (PE) provides a practical setting in which structured interventions can be delivered to this group. This study examined whether a 12-week PE program combining cooperative sports games with ball-sport activities was related to changes in physical fitness and psychological health among rural LBC. Forty sixth-grade LBC from a rural boarding primary school were randomly allocated to a mixed training group (MTG, n = 20) or a control group (CONG, n = 20). The MTG completed the mixed exercise program during regular PE classes for 12 weeks, with three 90-min sessions each week. The CONG continued with routine PE. Psychological health was measured using the Mental Health Test (MHT). Physical fitness was assessed with standard school-based indicators, including vital capacity, 50-m dash, 8 × 50-m shuttle run, rope skipping, sit-ups, sit-and-reach, and body mass index (BMI). Group-by-time effects were examined using repeated-measures ANOVA. Following the 12-week period, the MTG showed greater improvements in selected psychological and physical outcomes compared with the CONG. Significant group-by-time interactions were found for MHT total score (p < 0.001, d = -1.07), interpersonal anxiety (p = 0.007, d = -0.73), and self-blame tendency (p = 0.002, d = -1.41). Among physical fitness outcomes, significant group-by-time interactions were observed for vital capacity (p < 0.001, d = 0.97), 8 × 50-m shuttle run performance (p < 0.001, d = -0.90), 50-m dash performance (p = 0.002, d = -0.78), and rope skipping (p = 0.024, d = 0.73). However, BMI and sit-ups showed no significant group-by-time interactions. No exercise-related injuries or other adverse events occurred during the study. A 12-week mixed exercise program embedded in routine PE was associated with selective improvements in psychological health and physical fitness among rural LBC. These findings provide preliminary support for the potential value of combining cooperative sports games with ball-sport activities in school PE. Larger multi-site studies with longer follow-up are needed to confirm these findings.
To present a novel, nonlinear subspace modeling and joint k-q-space reconstruction technique for high-resolution, multi-band, multi-shell diffusion-weighted imaging (DWI). High b-value (> 1000 s/mm2), high resolution DWI has the drawback of generally low signal-to-noise ratios (SNRs). We present an approach that leverages a denoising autoencoder (DAE) to learn a latent subspace from biophysically simulated diffusion-weighted signals. The decoder of this network is then used in the forward operator of the image reconstruction process. The decoded latent images are scaled by the b 0 image, phase is added and processed as regular DWI images with the forward operator for multi-shot, multicoil, multi-slice, k-q-undersampled acquisition schemes. The performance is investigated with a multi-shell, multi-direction imaging brain scan and compared to the results of the multiplexed sensitivity-encoding (MUSE) reconstruction and locally low-rank (LLR) regularized reconstruction. The results are further validated by a bias and precision analysis of reconstructed fiber directions. Comparing the reconstructed data using the proposed method shows improved noise suppression compared to MUSE and more details than LLR-reconstructed images. Specifically, in the higher b-value domain, the reconstruction results show improved detectability of small structures. This bias and precision analysis showed minimal bias introduction, but higher precision with the proposed method. Our method combines deep learning, latent signal modeling, joint k-q-space reconstruction, and biophysical simulation for diffusion data and shows strong noise suppression and a high degree of detail in reconstructed diffusion-weighted images.
Predicting runoff and providing water quality early warnings becomes critical for timely monitoring of water resources. In particular, it needs to be robust under varying rainfall conditions, sensor noise and catchment conditions. We propose WRO-Water system, a hydrology-guided multi-head attention Transformer with mass-balance regularization for runoff forecasting, water quality prediction and anomaly-based early warning. The hydrology-guided attention is different from the default Transformer, which only uses content-based self-attention, by making the temporal attention scores dependent on rainfall, antecedent streamflow, evapotranspiration and latent storage behavior. To prevent that hydrologically inconsistent runoff predictions are made, a catchment-scale mass-balance residual is also incorporated as soft physical regularizer during supervised learning. A multitask learning model is developed that combines hydrometeorological variables, static catchment properties and water quality indicators. Evaluation was done with catchment-level partitioning and 10-fold cross-validation to minimize spatial leakage and to test generalization of results to held-out CAMELS catchments where supporting records from USGS and NOAA exists. WRO-Water achieved an NSE of 0.892 ± 0.014, RMSE of 8.31 ± 0.42 mm day-1, MAE of 5.18 ± 0.31 mm day-1, R2 of 0.913 ± 0.013, and correlation of 0.955 ± 0.008 for runoff prediction. For water quality forecasting, the model obtained R2 values of 0.946 ± 0.010 for pH, 0.951 ± 0.009 for dissolved oxygen, 0.938 ± 0.012 for turbidity, 0.932 ± 0.013 for nitrate, and 0.958 ± 0.008 for conductivity. The anomaly detection module achieved F1-scores from 95.09 ± 0.89% to 96.51 ± 0.70%, with early warning lead times of 4.37 ± 0.32 to 5.06 ± 0.34 h. These findings indicate that WRO-Water offers a physically constrained, accurate, and interpretable tool for early warning of water quality and prediction of runoff, and WRO-Water needs to be further validated in other external hydroclimatic regions and through other external monitoring networks.
The purpose of this study was to develop and validate a non-invasive radiomics-based model utilizing contrast-enhanced CT imaging of both intratumoral and peritumoral regions to predict preoperative microsatellite instability (MSI) status in gastric adenocarcinoma (GAC). A retrospective cohort comprising 193 patients with histologically confirmed GAC from two separate institutions (Centre 1: n = 115; Centre 2: n = 78) was enrolled. All patients underwent preoperative enhanced CT scans and immunohistochemical assays to determine MSI status. Tumor regions of interest (ROIs), specifically the intratumoral region (IR) and an extended area including the intratumoral and surrounding 3-mm peritumoral regions (IPR), were manually segmented on portal-phase CT images. Radiomics features were extracted from these defined ROIs. Following feature standardization, selection was conducted through inter-observer consistency (ICC), pairwise correlation analyses, and L1-regularized logistic regression. A radiomics signature was subsequently constructed via a support-vector machine (SVM) classifier. Feature contributions were quantified using SHapley Additive exPlanations (SHAP). Independent clinical variables and semantic features derived from CT were employed to develop a separate clinical model. A combined model was then formulated by integrating both radiomics and clinical variables. Receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA) were used to evaluate the predictive performance, calibration, and clinical utility of each model. The combined radiomics-clinical model integrating intratumoral and peritumoral features exhibited superior predictive capability (AUC = 0.891) compared to the standalone clinical model (AUC = 0.771), peritumoral radiomics model (AUC = 0.780), and tumor-clinical integrated model (AUC = 0.784). Calibration curves and decision-curve analysis suggested favorable calibration and potential clinical net benefit of the integrated model. The integrated model combining clinical variables with radiomic characteristics extracted from the intratumoral plus 3-mm peritumoral region showed promising ability for preoperative MSI prediction in GAC. Because this retrospective study included few MSI-H cases and used IHC as the reference standard, the model should be regarded as a preliminary imaging biomarker that requires prospective multicenter validation before clinical use.
Regular physical exercise can induce a multifaceted cardioprotective phenotype characterized by improved Ca2⁺ handling, mitochondrial resilience, redox buffering, autonomic regulation, and resistance to ischemia-reperfusion injury. Ca2⁺/calmodulin-dependent protein kinase II (CaMKII), particularly cardiac CaMKIIδ, is positioned at the intersection of these adaptive and maladaptive responses because it couples repetitive Ca2⁺ oscillations to excitation-contraction coupling, ion-channel regulation, transcriptional remodeling, mitochondrial stress signaling, and cell-death pathways. Current evidence indicates that CaMKII is not intrinsically protective or harmful; rather, its biological output depends on activation magnitude, duration, post-translational modification, isoform or splice-variant composition, and subcellular localization. Within physiological exercise contexts, transient and compartmentalized CaMKII signaling may support rate adaptation, phospholamban phosphorylation, sarcoplasmic reticulum Ca2⁺ reuptake, and contractile reserve. In contrast, chronic oxidative, inflammatory, catecholaminergic, or metabolic stress promotes autonomous CaMKII activation, RyR2-mediated Ca2⁺ leak, late Na⁺ current, mitochondrial dysfunction, arrhythmogenesis, and adverse remodeling. Exercise training appears to normalize this pathological signaling environment by improving redox and metabolic homeostasis, mitochondrial quality control, nitric oxide bioavailability, and autonomic balance, while preserving physiological CaMKII-dependent cardiac reserve. In this review, we synthesize current evidence on CaMKII as a context-dependent mediator of exercise-induced cardioprotection and discuss its implications for cardiovascular disease mechanisms, biomarker development, exercise prescription, and selective CaMKII-targeted therapy.
To determine whether hospitalization in an intensive care unit (ICU) with a routine multidrug resistant organisms (MDRO) screening policy increases appropriate initial antibiotic therapy (IAT) for treatment of patients with ICU-acquired bloodstream infections (BSIs). A sub-analysis of the EUROBACT-2 prospective international cohort study, including adult patients with ICU-acquired BSI. Exposure was admitting ICU's MDRO screening policy, classified as universal on-admission ± weekly screening versus no screening. Primary outcome was appropriate, empiric IAT given within 24 hours of BSI onset, that was concordant with antimicrobial susceptibilities. Associations were evaluated using mixed-effects logistic regression models. Subgroup analyses by BSI source, causative pathogen, local epidemiology and time period were completed. Overall, 1,800 patients with ICU-acquired BSIs from 304 ICUs were included. Patients were significantly more likely to receive appropriate IAT in the first 24 hours of the BSI onset when hospitalised in MDRO screening versus no screening ICUs (51.8% versus 43.1%; p<0.001). Considering patient demographics, clinical severity, clustering effects, and ICU-level factors the protective effect of MDRO screening remained significant (adjusted odds ratio 1.47, 95% CI 1.09-1.99; p=0.012). This association was strongest in patients with intra-abdominal or respiratory BSI sources, monomicrobial Gram-negative BSIs, ICUs with lower antimicrobial resistance prevalence, in the pre-COVID period and in ICUs performing both on-admission and weekly screening. More appropriate IAT for ICU-acquired BSIs was given when patients were hospitalised in ICUs practicing routine MDRO screening. These results support the role of regular screening in improving empiric antibiotic decision making for ICU-acquired BSIs.
A 46-year-old male patient had been undergoing treatment for hidradenitis suppurativa for over 10 years and had undergone surgical treatment 9 and 7 years before visiting our hospital and subsequently received only conservative treatment. The patient had a history of diabetes mellitus and was diagnosed with stage III hidradenitis suppurativa according to Hurley's classification. He had scars and fistulas, particularly, on the buttocks, and had severe anemia. This anemia appeared to be associated with bleeding from the lesions and chronic inflammation. A colostomy was performed, which eliminated the need for regular blood transfusions, and his hemoglobin level improved to within normal limits after two-stage excisional surgeries, followed by reconstruction with split-thickness skin grafting. Although colostomy can help manage anemia, a serious complication of hidradenitis suppurativa, aggressive surgical intervention, including colostomy, may be necessary for patients with refractory disease to prevent deterioration of their general condition.
Examination of round sardinella Sardinella aurita Valenciennes, 1847 (Clupeidae) from the Gulf of Tunis (Tunisia) revealed the first local and Mediterranean record of Anthobothrium sp. 1 sensu Jensen & Bullard, 2010 (Tetraphyllidea incertae sedis, Anthobothrium). Nodular lesions containing multiple larvae were detected at the proximal end of the pyloric caeca, and free plerocercoids were observed in the intestinal lumen and stomach. The newly generated LSU rDNA sequences shared 100% nucleotide identity with adult Anthobothrium sp. 1B from the blacktip shark Carcharhinus limbatus Valenciennes, 1839 and larvae from the largehead hairtail Trichiurus lepturus L., both collected from the Gulf of Mexico (Florida and Mississippi, USA). Furthermore, they exhibited a minor 2.1% sequence divergence from related lineages within the same complex found in the Atlantic sharpnose shark Rhizoprionodon terranovae Richardson, 1836 and the hardhead sea catfish Ariopsis felis (Linnaeus, 1766) from the same Gulf of Mexico geolocations. COI sequences showed low variability, with p-distances ranging from 0.18% to 0.92% (corresponding to 1-5 nucleotide differences across 544 base pairs), consistent with the presence of a single species. Scanning electron microscopy of the cestode larva revealed aristate gladiate spinitriches and capilliform filitriches within the acetabula, and capilliform filitriches on the scolex peduncle. Histopathological analysis of nodular lesions showed clusters of multiple larvae, predominantly located within the caecal lumen. Host tissues exhibited localised mucosal alterations, characterised by elements of mucosal atrophy, villus compression and epithelial degeneration. These changes were primarily the result of mechanical pressure exerted by the larvae within the caecal lumen. A focal accumulation of mucous cells (presumptive goblet cells) was observed in affected areas. While primary structural alterations were confined to the mucosa, inflammatory infiltration within the submucosa appeared minimal. Despite this typical localised tissue response, S. aurita appears to be a regular second intermediate host, whereas other clupeids may also act as second intermediate hosts and clupeid-feeding teleosts as paratenic hosts. This finding extends the distribution of Anthobothrium sp. 1 from the western Atlantic to the western Mediterranean Sea, where the definitive host remains unknown.
Anticonvulsants are the drugs given for managing epilepsy and some other types of neurological disorders; however, their long-term use is increasingly suspected of causing adverse skeletal outcomes, including osteomalacia. Osteomalacia is a condition marked by defective mineralization of bone, leading to bone softening, bone pain, muscle weakness, and predisposition to fractures. The disruption of vitamin D metabolism, impaired calcium absorption, and altered bone turnover are mechanisms attributed to several commonly used anticonvulsants, especially enzyme-inducing agents such as phenytoin, carbamazepine, and phenobarbital, in contributing to osteomalacia. Hence, this review aims to provide detailed information about the pathophysiology, clinical manifestations, diagnosis, and treatment of anticonvulsant-induced osteomalacia. The review places further emphasis on the importance of regular monitoring of bone health in individuals receiving long-term antiepileptic treatment, supplementation, lifestyle interventions, and interprofessional care. A proper understanding of this preventable complication will certainly help healthcare providers to minimize the impact in these patients and improve outcomes.
Paratesticular tumors are rare neoplasms, with liposarcomas of the spermatic cord representing an uncommon malignant subtype. These tumors typically grow slowly and may attain a considerable size before diagnosis because of their indolent clinical course. We report the case of a 65-year-old male patient who presented with a progressively enlarging left-sided scrotal swelling of five years' duration. Based on clinical examination and ultrasonographic findings, a left paratesticular neoplasm was suspected. Contrast-enhanced computed tomography revealed a large heterogeneous fat-containing lesion encasing the spermatic cord. The patient underwent complete surgical excision with left radical orchidectomy. Histopathological features (mature adipocytes with fibrous septae and atypical stromal cells), supported by immunohistochemistry (MDM2 intense nuclear positivity), confirmed the diagnosis of well-differentiated liposarcoma. The postoperative course was uneventful, and no adjuvant treatment was administered; he was kept on regular follow-up. He remains free of local recurrence and distant metastasis at 24 months of follow-up. This case highlights the importance of considering paratesticular liposarcoma in the differential diagnosis, particularly in patients presenting with slowly progressive scrotal swellings. Early diagnosis and complete surgical excision with negative margins remain the cornerstone of management and are essential for achieving optimal disease control and favorable long-term outcomes.
Sleep hygiene strategies (SHS) are practical, evidence-informed recommendations to enhance both the quantity and quality of sleep in athletes. However, little is known about how these strategies could be communicated and implemented in practice. The primary objective of this study is to investigate how different methods of delivering SHS (written vs. verbal) affect sleep hygiene and sleep parameters in athletes. The study was a three-arms randomized controlled trial (ClinicalTrials.gov Identifier: NCT07083544) involving track and field athletes competing at the regional or national level (N.=66). Athletes were randomized to either a control group (CON=22), a written SHS group (W-SHS=22), or a verbal SHS group (V-SHS=22). Sleep characteristics were assessed by actigraphy and sleep diary during a ten-day baseline period (T0) and a ten-day intervention period (T1). Six objective sleep parameters and the Sleep Regularity Index were assessed. Participants also completed a training diary and the Sleep Hygiene Index (SHI). No statistical differences were found between and within groups in training and sleep parameters, but SHI scores improved significantly in the intervention groups between T0 and T1, with differences compared to the control group. A non-significant improvement in total sleep time was observed in the intervention groups, primarily due to earlier bedtimes. While significant differences in objective sleep measures were not observed, the trends suggest that both written and verbal SHS interventions can modestly improve sleep-related behaviors, particularly by encouraging earlier bedtimes and slightly extending total sleep duration.
To retrospectively analyze the early death of patients with newly diagnosed multiple myeloma (NDMM) treated with daratumumab, build a risk warning model and verify its clinical decision-making benefits. The clinical data of 112 NDMM patients treated with daratumumab combination therapy in Tangshan Gongren Hospital from June 2018 to June 2022 were retrospectively collected as the training set, and the clinical data of 78 NDMM patients who received daratumumab combination therapy in the same period were collected as the validation set. According to whether early death occurred during regular follow-up (OS <24 months), the patients were divided into early death group (26 cases) and non-early death group (86 cases). The differences of clinical data between the two groups were analyzed, and Kaplan-Meier survival curves were used to analyze the survival difference of patients with different efficacy. Univariate and multivariate Cox regression analysis were used to analyze the independent risk factors affecting early death of NDMM patients treated with daratumumab. A warning nomogram model for the risk of early death was established, and the predictive performance was analyzed by receiver operating characteristic (ROC) curve and verified internally. According to whether the efficacy of daratumumab treatment achieved partial response (PR), the patients were divided into <PR group (32 cases) and ≥PR group (80 cases). Kaplan-Meier analysis found that the median OS of both groups were not reached, while the OS of patients with efficacy ≥PR was significantly longer than that of patients with efficacy <PR (log-rank χ2=14.225, P <0.001). Multivariate Cox regression analysis showed that older age, R-ISS stage Ⅲ, elevated hs-CRP, and efficacy <PR were independent risk factors for early death in NDMM patients (all P <0.05), and a nomogram model for early death risk in NDMM patients was constructed. ROC analysis and DeLong test showed that the AUC of the nomogram model was 0.894(95%CI : 0.828-0.959), which was higher than that of each individual model, and the differences were statistically significant (all P <0.05). Internal and external validation showed that the nomogram model was stable and had a positive net benefit. The OS of NDMM patients who did not reach PR after daratumumab treatment can be affected. Daratumumab treatment early death risk warning model for NDMM has good efficacy, and can be targeted at high-risk population for intensive treatment to improve prognosis. 达雷妥尤单抗治疗新诊断多发性骨髓瘤患者早期死亡风险预警多模型研究及临床决策分析. 分析达雷妥尤单抗治疗新诊断多发性骨髓瘤（NDMM）患者早期死亡情况，构建发生风险预警模型并验证其临床决策效益。. 回顾性收集2018年6月至2022年6月于唐山市工人医院接受含达雷妥尤单抗联合方案治疗的112例NDMM患者临床资料，设为训练集；收集同期接受含达雷妥尤单抗联合方案治疗的78例NDMM患者临床资料，作为验证集。依据定期随访中是否发生早期死亡（总生存期OS <24个月），将患者划分为发生早期死亡组（26例）与未发生早期死亡组（86例）。对两组患者临床相关资料行差异性分析，Kaplan-Meier生存曲线分析不同疗效患者生存期差异。单因素和多因素Cox回归分析NDMM达雷妥尤单抗治疗早期死亡的独立危险因素。建立早期死亡发生风险预警列线图模型，通过ROC曲线分析预测效能并进行内部验证。. 根据治疗疗效是否达到部分缓解（PR），将所有患者分为<PR组（32例）与≥PR组（80例）。Kaplan-Meier分析结果显示，两组患者的中位OS均未达到，而≥PR患者OS明显长于<PR患者（log-rank χ2=14.225，P <0.001）。多因素Cox回归分析结果显示，年龄越大、R-ISS分期Ⅲ期、hs-CRP升高、疗效未达到PR为NDMM早期死亡的独立危险因素（均P <0.05），并构建NDMM患者早期死亡风险预警列线图模型。ROC分析和DeLong法检验结果显示，列线图模型的AUC值为0.894(95%CI :0.828-0.959)，高于各单个变量的AUC，比较差异有统计学意义（均P <0.05）。内部及外部验证结果显示，该列线图模型较为稳定，且有正向净收益率。. 达雷妥尤单抗治疗未达PR的NDMM可影响患者OS。NDMM达雷妥尤单抗治疗早期死亡风险预警模型效能良好，可针对高风险人群进行强化治疗以改善预后。.
Seafood provides essential nutritional benefits but represents the primary dietary route of exposure to methylmercury (MeHg). Population-level evidence linking adult seafood consumption behavior to MeHg risk awareness in Saudi Arabia remains absent. This study aimed to characterize seafood consumption patterns, estimate MeHg hazard recognition, and identify independent predictors of high-risk consumption and mercury risk awareness among Saudi adults. This nationwide cross-sectional survey enrolled 1,021 adults across all 13 Saudi administrative regions (January-April 2026) and used two pre-specified binary logistic regression models-one examining predictors of high-risk seafood consumption (Model 1) and one examining predictors of mercury risk awareness (Model 2). Regular seafood consumption was reported by 47.4% of participants; only 19.7% identified mercury as a health concern. High-risk consumption, operationalized using FDA/U.S. EPA advisory thresholds and Gulf-region contamination data, was identified in 53.3% of participants (sensitivity range across five alternative definitions: 24.9-70.4%). Women demonstrated higher MeHg-specific awareness (23.6% vs. 16.5%; p = 0.005) and greater food-safety knowledge (1.29 ± 1.91 vs. 0.71 ± 1.42; p < 0.001). Food-safety knowledge strongly predicted mercury awareness (OR = 4.000, 95% CI [3.350-4.777]) but was not associated with consumption behavior (OR = 0.997; p = 0.950). Coastal residence (OR = 3.019), older age (≥50 years: OR = 3.494), female sex (OR = 0.534), and lower educational attainment independently predicted high-risk consumption. Consistent with our objective of evaluating whether food-safety knowledge translates into safer seafood choices, this knowledge-behavior gap was robust across all five sensitivity specifications, confirming a structural-rather than informational-dissociation between awareness and behavior. Species-specific, geographically targeted interventions, rather than general knowledge-based campaigns, are therefore required to reduce the risk of MeHg exposure among Saudi adults.
BACKGROUND Stevens-Johnson syndrome (SJS) is characterized by widespread, epidermal necrosis and mucosal involvement mediated by a delayed-type hypersensitivity reaction. Although rapidly progressive epidermal detachment is known to result in blister formation, pustular lesions are rare in SJS. CASE REPORT A 25-year-old male patient with no significant medical history or regular medication presented to the emergency department with a fever and rash. The fever had developed 7 days before the current presentation and was followed 4 days later by lip swelling, conjunctival hyperemia, and sore throat, which caused difficulty with oral intake. Two days before presentation, a generalized rash and dysuria developed, prompting evaluation at our hospital. A clinical examination found multiple, 3-mm pustules surrounding erythema on the face, chest, and back. Scattered erosions were observed on less than 10% of body surface, including the distal extremities, lips, buccal mucosa, and genital area. The conjunctivae displayed marked pseudomembrane formation. Histopathological analysis found that the erosions contained necrotic keratinocytes in the epidermis, with mild vacuolar changes at the dermo-epidermal junction, while the pustules contained serous exudate with scattered neutrophils. Based on these findings, SJS was diagnosed. A drug-induced lymphocyte stimulation test was positive for loxoprofen. The patient responded well to prednisolone therapy. CONCLUSIONS Although no drug exposure or infection preceding the symptoms was identified at admission, SJS was diagnosed by exclusion on the basis of the clinical manifestations and diagnostic criteria. A drug-induced lymphocyte stimulation test may help identify the causative drug. Neutrophilic infiltration into blisters formed by progressive, epidermal necrosis may occasionally result in pustule-like eruptions in SJS.
Breast cancer is often treated with tamoxifen, a drug that can cause ocular side effects, including toxic retinopathy. Multimodal imaging, particularly optical coherence tomography (OCT), has improved the detection of early lesions such as foveal pseudocysts, thus increasing the prevalence of this complication. We present a case of tamoxifen-induced retinopathy in a patient treated for four years who developed decreased visual acuity with irreversible retinal lesions in the right eye despite discontinuation of the treatment. OCT was essential in characterizing the lesions. The pathophysiology remains poorly understood, but involvement of Müller cells and glutamate accumulation in the retinal pigment epithelium are suspected. Toxicity depends on cumulative dose, duration of treatment, and individual factors. Initial ophthalmologic screening and regular OCT monitoring are recommended to detect retinal damage early. In case of lesions, substitution with an aromatase inhibitor is often considered to limit lesion progression and preserve vision. Le cancer du sein est souvent traité par tamoxifène, médicament qui peut entraîner des effets indésirables oculaires, notamment une rétinopathie toxique. Grâce à l’imagerie multimodale, en particulier la tomographie par cohérence optique (OCT : «Optical Coherence Tomography»), les lésions précoces, comme les pseudokystes fovéolaires, sont mieux détectées, ce qui augmente la prévalence de cette complication. Nous présentons un cas de rétinopathie induite par le tamoxifène chez une patiente traitée depuis quatre ans par hormothérapie, qui a développé une baisse d’acuité visuelle avec des lésions rétiniennes irréversibles à l’œil droit malgré l’arrêt du traitement. L’OCT a été essentiel pour caractériser les lésions. La physiopathologie de cette complication reste mal comprise, mais l’implication des cellules de Müller et l’accumulation de glutamate dans l’épithélium pigmentaire rétinien sont suspectées. La toxicité dépend de la dose cumulée, de la durée du traitement et de facteurs individuels. Un dépistage ophtalmologique initial et un suivi régulier par OCT sont recommandés pour détecter tôt les atteintes rétiniennes. En cas de lésion, la substitution par un inhibiteur de l’aromatase est souvent envisagée pour limiter la progression des lésions et préserver la vision.