The lysine-specific demethylase 1 (LSD1) inhibitor bomedemstat in myelofibrosis: results from a phase 1/2 study.

Objective: To analyze the risk factors for poor prognosis in children with steroid-resistant nephrotic syndrome (SRNS) and to construct and validate a prognostic model. Methods: A retrospective cohort study was conducted. Clinical data of 456 children with SRNS who were initially diagnosed and hospitalized at the Children's Hospital of Chongqing Medical University from January 2009 to December 2024 was collected, including general information, laboratory and pathological indicators, gene types, treatment, and prognosis. Follow-up was conducted for more than 12 months. The endpoint event was defined as a decrease in the estimated glomerular filtration rate (eGFR) of more than 30% compared to the baseline for three consecutive times (with an interval of at least one month between each measurement). The patients were divided into the event group and the non-event group based on whether the endpoint event occurred. Independent sample t-test, Mann-Whitney U test, test χ2, or Fisher's exact probability test were used for comparison between groups. Multivariate Logistic regression was used to rank the importance of variables to screen for characteristic variables. The top 6 ranked characteristic variables were used to construct four machine learning models using Python: extreme gradient boosting, random forest, support vector machine, and logistic regression. The area under the receiver operating characteristic curve (AUC), accuracy, specificity, sensitivity, and F1 score were used to evaluate the discrimination and performance of the models. Calibration curves and clinical decision curves were drawn to assess the prediction accuracy and clinical net benefit of the models. The Shapley Additive Explanations (SHAP) method was applied to analyze the contribution of features. Results: Among the 456 children, 306 were male and 150 were female. The age of onset was 4.1 (2.3, 8.0) years, and the follow-up time was 2.2 (1.0, 4.0) years. There were 195 cases (42.7%) in the event group and 261 cases (57.3%) in the non-event group. The time of occurrence of the endpoint event in the event group was 1.0 (0.5, 2.5) years. Univariate analysis showed that there were statistically significant differences between the two groups in initial serum creatinine, initial eGFR, eGFR change rate after 3 months of treatment, gender, calcineurin inhibitor (CNI) treatment response, gene variation, white blood cell count, absolute monocyte count, blood urea nitrogen, and urine red blood cells (all P<0.05). The top 6 characteristic variables, including the eGFR change rate after 3 months of treatment, genetic variation, baseline eGFR, CNI treatment responsiveness, gender and baseline serum creatinine (the AUC decrease percentages of 20.1%, 9.4%, 1.6%, 1.0%, 0.3% and 0.1% respectively after permutation test). Among the four machine learning models, the random forest model performed the best (test set AUC was 0.77 (95%CI 0.73-0.81), accuracy 73.9%, specificity 78.5%, sensitivity 71.2%, and F1 score 68.9%). The Hosmer-Lemeshow test showed that the predicted risk and actual risk of the random forest model were in good agreement (χ2=7.72, P=0.461); the clinical decision curve showed that the random forest model performed best and had the highest net benefit within a certain threshold range (0-0.5). Through SHAP, it was determined that the eGFR change rate after 3 months of treatment, initial eGFR, gene variation, and CNI treatment response were important predictors of poor prognosis in SRNS (average SHAP absolute values were 0.18, 0.08, 0.07 and 0.02, respectively). Conclusions: A random forest model was constructed based on machine learning and explained using the SHAP method. The eGFR change rate after 3 months of treatment, initial eGFR, gene variation, and CNI treatment response are important factors affecting prognosis.

Short-Term Results of Vascular Interventions for Acute Superior Mesenteric Artery Embolism.

A 10-week feeding trial was conducted to investigate the effects of dietary supplementation of Cladophora glomerata (CG) powder on growth, feed utilization, carcass composition, hematology, and expression of genes related to growth and immunity in ornamental goldfish ( Carassius auratus ) . Five isonitrogenous and isolipidic diets containing 0 (control), 25, 50, 75, and 100 g/kg of CG (CG25 - CG100) were fed to triplicate groups of 20 fish (initial body weight: 5.02 ± 0.00 g) to apparent satiation for 10 weeks. At the end of the trial, dietary CG supplementation linearly improved growth and protein efficiency, with a quadratic increase in protein productive value. Crude protein and fat increased both linearly and quadratically, with CG100 showing the highest levels. The a* and b* values increased linearly in all organs, with b* in the head and tail showing a quadratic response. Furthermore, CG at 50 -100 g/kg significantly increased total carotenoids content in fins, liver, and serum, while 75–100 g/kg increased the levels in muscle and skin. White blood cell count, red blood cell count, and hematocrit levels increased linearly and quadratically, while hemoglobin increased linearly. Conversely, AST, triglycerides, and LDL-c cholesterol decreased versus the control group. Supplementation of CG higher than 50 g/kg exhibited a linear increase in the liver growth-related genes (IGF-1, IGF-2) and linear and quadratic increase in the expression of anti-inflammatory (IL-10) and pro-inflammatory (TNF-α, IL-1α) cytokine genes in goldfish. The hepatocyte histomorphology of goldfish fed diets supplemented with CG exhibited no significant differences compared to the control group. In conclusion, supplementation of diets with 50–100 g/kg CG markedly enhanced growth performance and increased a * pigmentation values in the head, abdomen, and tail regions. This inclusion level also elevated total carotenoid concentrations in the fins, muscle, and serum, and induced the upregulation of genes related to growth (IGF-1, IGF-2) and immune response (TNF-α, IL-1α, IL-10), along with lysozyme mRNA expression. These findings suggest that C. glomerata supplementation at 50–100 g/kg could contribute to enhanced growth and modulation of pigmentation and immune-related responses in goldfish. • Cladophora glomerata (CG) meal improved growth and feed utilization with reduced FCR. • Supplementing CG at 50 g/kg significantly enhanced head, abdominal, and tail coloration. • CG supplementation above 50 g/kg upregulated immune and growth-related genes expression.

The Total Thrombus-formation Analysis System 01 (T-TAS 01) is an advanced microchip-based device that enables quantitative assessment of blood thrombogenicity. However, broader clinical implementation remains limited by the lack of well-established reference intervals (RIs) in healthy, antithrombotic drug-naïve individuals. This study aimed to define RIs and identify clinical determinants of blood thrombogenicity in antithrombotic drug-naïve adults using T-TAS 01. Blood thrombogenicity was measured using T-TAS 01 in 319 adults without antithrombotic therapy who underwent health checkups at the Miyakonojo Health Service Center. The T-TAS 01 parameters, PL18-AUC10 and AR10-AUC30, were calculated as the areas under the flow-pressure curves of the PL-chip (type I collagen-coated) and the AR-chip (type I collagen and tissue factor-coated), respectively. Their associations with clinical parameters were assessed using multivariate regression analysis. The median age was 46.0 years; 64.3% of participants were female, and 82.1% had no hypertension, dyslipidemia, or diabetes. The median platelet count was 247 × 109/L. The median PL18-AUC10 and AR10-AUC30 values were 392.3 and 1335.9, with RIs of 236.3 to 468.1 and 1010.0 to 1496.2, respectively. PL18-AUC10 was independently associated with white blood cell count (coefficient, 5.15; 95% CI, 0.88-9.41) and platelet count (0.36; 95% CI, 0.25-0.47), whereas AR10-AUC30 was independently associated with body mass index (4.06; 95% CI, 0.06-8.06), platelet count (0.79; 95% CI, 0.52-1.06), and γ-glutamyl transpeptidase (-0.54; 95% CI, -0.90 to -0.18). Our findings provide foundational reference data for the clinical application of T-TAS 01 and support its potential as a point-of-care tool for individualized assessment of thrombogenicity.

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a life-sustaining therapy for severe refractory cardiogenic shock. Although VA-ECMO provides various degrees of cardiopulmonary support, mortality rates remain high. Serum biomarkers have potential to identify the rising risk of mortality in patients receiving ECMO, but evidence supporting their prognostic value is inconsistent. This study aims to systematically investigate existing evidence on the relationship between biomarkers and mortality in adult patients with refractory cardiogenic shock undergoing VA-ECMO support. A systematic review was conducted conforming to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Analogous search strings were developed to complete a comprehensive literature search across multiple databases that included Embase, Scopus, PubMed, and Cumulative Index to Nursing and Allied Health Literature (CINAHL). Search limits include studies published in the last 5years (>2018) and in the English language. The inclusion criteria were: all genders aged 18 and older being treated for cardiogenic shock with VA-ECMO and intra-ECMO biomarker data with corresponding mortality data. Biomarkers included in the criteria were: lactate, creatinine, bilirubin, aspartate transaminase (AST), alanine transaminase (ALT), troponin, C-reactive protein (CRP), and white blood cell (WBC) count. Identified articles were included within the main findings after unanimous approval by all authors. The quality of the evidence was assessed systematically utilizing a standardized and validated checklist. Our search yielded 1,033 studies, with 650 studies remaining after the removal of duplicates, leaving 538 studies to be screened for title and abstract study relevance. Subsequently, 112 studies remained for full-text review. Reasons for exclusion during full-text review include conference abstract, no mention of specific biomarkers, and wrong comparison of treatment modalities. Five studies remained for data extraction. Data gathered from five retrospective cohort studies reported a total of 589 patients supported by VA-ECMO following a diagnosis of cardiogenic shock, with the most common inciting factor being postcardiac surgery. Most patients were male. The age range for all participants was between 45 and 77years. Common comorbidities include diabetes mellitus, hypertension, and vascular disease. Overall mortality was 59.9 % (353/589) based on survival to 30-day post-ECMO initiation or hospital discharge. In three of the studies, the patients in the survivor cohort had statistically significant lower intra-ECMO lactate levels compared to the non-survivors (p<0.01). One of the studies found statistically significant differences between survivors and non-survivors in the intra-ECMO values for serum lactate (p<0.001), creatinine (p<0.023), bilirubin (p<0.001), AST (p<0.05), and ALT (p<0.05). Another study reported statistically significant differences in nadir lactate levels through 24 and 48 h of ECMO initiation in survivors vs. non-survivors (p=0.001 and p=0.001 respectively). Serum lactate was the biomarker most utilized to assess the risk of mortality. Serum creatinine (Scr), bilirubin, AST, and ALT also demonstrated significance in predicting mortality, although not as widely studied as serum lactate. Future research is needed to further investigate the usage of Scr, bilirubin, AST, and ALT to better assess their significance, regarding VA-ECMO mortality in patients diagnosed with cardiogenic shock. Further research is also warranted to investigate the minimal concentration of these biomarkers and their association with mortality to allow clinicians a better predictor of a patient's mortality risk while receiving VA-ECMO.

Despite the preweaning period being critical for immune system development, heat abatement for calves in summer is often overlooked during this early-life period. Herein, we evaluated selected markers of innate and adaptive immunity development in outdoor hutch-housed Holstein dairy heifers with 2 types of ventilation during a Midwestern summer. Heifer calves were housed in outdoor hutches with passive (PASS; 0.07 m/s natural air speed, n = 16) or active ventilation (ACT; 1.1 m/s air speed via solar-powered fans, n = 16) from birth to 28 d of life. At d 28, fans were turned off, and all heifers were naturally ventilated. Heifers were weaned at 49 d and monitored until 56 d of age. Blood samples were collected at various stages of the preweaning period (d 1-56) to assess IgG, glucose, blood hematology, gene expression, and functional assays. At birth, circulating IgG, glucose, and hematology parameters were not different between groups. Relative to heifers exposed to PASS, ACT heifers had reduced white blood cell, monocyte, neutrophil, and lymphocyte counts, particularly the first 28 d. The ACT heifers had a greater percentage of neutrophils with phagocytic activity on d 28 and 42 of life, and tended to have neutrophils with greater percentage of oxidative burst on d 42. The mRNA expression of haptoglobin, IL-6, IL-8, IFN-γ, and NFKβ1 was downregulated in peripheral blood leukocytes of PASS heifers, relative to ACT. Providing active ventilation to heifers during the first 4 wk of life in summer enhances neutrophil phagocytic capacity, reduces circulating neutrophil and lymphocyte counts, and downregulates the expression of key pro-inflammatory cytokine and interleukin genes in peripheral leukocytes.

Development of a clinical prediction model for discriminative factors of lower respiratory tract infections in patients presenting with fever: A single-center retrospective study.

Shenfu decoction attenuates radiation-induced heart disease by modulating the P53-MDM2 complex and the STAT1-BATF2 axis.

Cultivar-dependent immunometabolic effects of pigmented rice extracts in immunosuppressed obese mice.

We present a rare case of a 7-month-old infant with a complex invasive Streptococcus pneumoniae infection involving rib osteomyelitis, a pulmonary abscess, and a chest wall abscess. The patient presented with persistent fever and no respiratory symptoms. On day 9, chest radiography was performed because of persistent fever and marked leukocytosis, consistent with the American College of Radiology Appropriateness Criteria that recommend imaging in febrile infants with high fever (≥39°C) or elevated white blood cell counts (≥20 000/mm3). On day 14, the emergence of a chest wall mass prompted escalation to ultrasonography, which provided noninvasive assessment of soft tissue involvement. Subsequent contrast-enhanced computed tomography scans were undertaken to delineate the extent of contiguous spread, evaluate rib destruction, and exclude alternative diagnoses. Microbiological cultures of sputum and aspirated pus, along with metagenomic sequencing, confirmed the presence of macrolide-resistant S. pneumoniae. Because of benzylpenicillin and cephalosporin allergy, intravenous linezolid was selected, resulting in rapid clinical improvement. A 6-week course (intravenous infusion followed by oral) led to complete resolution on imaging, with no recurrence over 5years. This case underscores the importance of appropriate imaging modalities in febrile infants without respiratory symptoms and the need to consider extrapulmonary spread in chest wall masses. It highlights the diagnostic value of metagenomic sequencing and susceptibility testing in guiding individualized antimicrobial therapy, particularly in macrolide-resistant settings.

Aumolertinib with or without chemotherapy in EGFR-mutated advanced non-small-cell lung cancer (AENEAS2): an open-label, multicentre, randomised, controlled, phase 3 trial.

Comparison of postoperative recovery indicators between stereoelectroencephalography and subdural grid electrode implantation for drug-resistant epilepsy.

BackgroundThe diagnosis of neurosyphilis is challenging due to the limited sensitivity of cerebrospinal fluid Venereal Disease Research Laboratory (VDRL) test. Late latent syphilis is defined as positive treponemal serology without clinical manifestations and untreated infection for more than 1year. Symptomatic or asymptomatic neurosyphilis is diagnosed based on cerebrospinal fluid findings and clinical symptoms. This cross-sectional study investigated serum Toluidine Red Unheated Serum Test (TRUST) titer and cerebrospinal fluid inflammatory markers as predictors of neurosyphilis in HIV-negative patients with late latent syphilis.MethodsA total of 196 HIV-negative patients with late latent syphilis who underwent lumbar puncture at the Shanghai Skin Disease Hospital between September 2009 and December 2022 were included. Neurosyphilis was defined as a reactive cerebrospinal fluid (CSF) Venereal Disease Research Laboratory (VDRL). Demographic, clinical, and laboratory variables were analyzed using logistic regression and receiver operating characteristic curves.ResultsOf the 196 patients, 123 (63%) were diagnosed with neurosyphilis. In multivariable analysis, higher serum TRUST titer, elevated CSF white blood cell count, and increased CSF protein levels were independently associated with neurosyphilis. Optimal cutoffs were serum TRUST ≥1:16, CSF protein ≥0.7g/L, and CSF white blood cell ≥10 cells/μL. The CSF white blood cell count showed the highest diagnostic accuracy (AUC = 0.90). The combination of these three variables improved the sensitivity and specificity by 89% and 90%, respectively.ConclusionAmong HIV-negative patients with late latent syphilis, elevated serum TRUST titer, CSF white blood cell count, and a CSF protein level ≥0.7g/L are independently associated with neurosyphilis. The composite panel serves as reliable tool for post-lumbar puncture risk stratification and interpretation of CSF findings in routine practice.

Evaluation of the relationship between signal time in blood cultures and clinical findings in brucellosis cases.

Circulating metabolic and inflammatory biomarkers in MINOCA: pathophysiologic mechanisms and clinical implications.

Background: Bovine anaplasmosis is a communicable disease transmitted via ticks, which carries significant veterinary and economic implications. Data from western Iraq remains scarce despite high cattle exposure to vector-borne infections. Objective: To determine the incidence of Anaplasma marginale in cattle in Anbar Province, compare the diagnostic performance of microscopy, ELISA, and PCR, and assess associated haematological changes. Methodology: Between January and December 2024, three hundred blood samples were drawn from cattle (1–10 years, both sexes) across 20 farms in Haditha, Heet, Al-Qaim, and Rutba districts; Giemsa-stained smears, a commercial ELISA, and PCR targeting the msp5 gene were used for diagnosis. Haematological parameters (RBC, Hb, PCV, WBC) were measured using an automated analyser. Prevalence was determined by sex, age, and season, while haematological data were compared by t-tests (α = 0.05). Results: Prevalence was 28.0% by microscopy, 36.3% by ELISA, and 41.3% by PCR, with PCR being most sensitive. Infection rate was higher among females (46.9%) compared to males (33.6%), and in older cattle than in younger ones; Peak rates occurred in the summer (62.6%), with the lowest rates in winter (17.3%). Infected cattle had reduced Hb, PCV, RBC, and elevated WBC counts. Conclusion: This study provides the first detailed epidemiological report on bovine anaplasmosis in western Iraq. The results confirm that PCR is the most sensitive tool, underlining host and seasonal influences on infection and revealing distinct haematological alterations. These findings provide a surveillance baseline and support control strategies against A. marginale in endemic regions.

To identify predictors of true appendicitis among children with a Pediatric Appendicitis Score (PAS) <4 and to develop a model for detecting missed appendicitis in this low-risk population. A prospective study including consecutive children aged 2-14 y presenting with suspected appendicitis was conducted between January 2022 and October 2025. Only children with PAS <4 were included in the analysis. Among 1174 children evaluated, 404 (34.4%) had PAS <4 and were included. Of these, 39 (9.6%) had confirmed appendicitis. The mean age of this cohort was 9.8 ± 2.6 y, and males accounted for 48.5% of the population. Compared with non-appendicitis cases, affected children had higher rates of vomiting (61.5% vs. 40.3%, p = 0.011), higher median WBC counts (8.8 vs. 7.7 × 10⁹/L, p = 0.001), and higher CRP levels (17 vs. 5mg/L, p = 0.001). On multivariable analysis, WBC >8.8 × 10⁹/L (OR 2.77; p = 0.012), CRP ≥10mg/L (OR 3.17; p = 0.005), and positive ultrasound (OR 17.36; p <0.001) were independent predictors. Ultrasound showed the highest diagnostic accuracy (85%) and negative predictive value (97%). Nearly 10% of children with PAS <4 had confirmed appendicitis. Combining inflammatory markers with targeted ultrasound may improve early detection of missed appendicitis in low-risk pediatric patients.

The objective of this study was to evaluate the performance of multiple machine learning algorithms to provide evidence supporting early intervention for high-risk patients with oral and maxillofacial space infections (OMSI), thereby reducing complication rates and improving overall clinical outcomes. A retrospective cohort study was performed to analyse clinical data from 432 medical records, with a focus on key variables related to disease severity and treatment outcomes. The data included age, gender, height, weight, BMI, blood test results, such as the CRP, white blood cell count, neutrophil count, lymphocyte count, monocyte count, albumin, potassium, sodium, chlorine, calcium, uric acid, blood urea nitrogen, PCT, fibrinogen, blood glucose, vital signs, such as body temperature, heart rate, systolic blood pressure, diastolic blood pressure, respiration, days before hospitalization, the extent of mouth opening, the space of infected spaces, and the source of infection. We summarized the predictive performance of three models-Logistic regression, Random Forest, and XGBoost-across three key clinical outcomes. For predicting hospital stay duration, Logistic regression performed best. For predicting ICU admission, XGBoost exhibited the strongest performance. For predicting surgical intervention, Logistic regression achieved the optimal overall performance, while XGBoost and Random Forest demonstrated the highest specificity. In summary, we have successfully developed, validated, and compared predictive models for key clinical outcomes in patients with OMSI. They further hold promise for ultimately optimizing the diagnostic and therapeutic workflow and improving outcomes for patients with this common yet potentially life-threatening condition. Not applicable. Not applicable.

Streptococcus pyogenes meningitis is a rare but potentially life-threatening infection in infancy. It can occur as a primary infection or as a complication of viral illnesses such as varicella, which can increase the risk of invasive bacterial disease. We report a previously healthy 3-month-old boy who presented with fever, poor feeding, and a vesicular rash following varicella exposure. Despite outpatient acyclovir therapy, the patient developed dehydration and persistent fever. Cerebrospinal fluid (CSF) analysis revealed markedly elevated white blood cell counts, elevated protein, and low glucose. CSF Gram stain demonstrated gram-positive cocci in pairs, and CSF culture subsequently confirmed Streptococcus pyogenes (Group A Streptococcus) that was susceptible to penicillin, vancomycin, amoxicillin/clavulanic acid, ceftriaxone, teicoplanin and cefotaxime. The patient received broad-spectrum antibiotics, antivirals, and supportive care. Despite escalation to a tertiary pediatric intensive care unit (PICU), he developed progressive cerebral edema, refractory seizures, and loss of brainstem reflexes. Brain death was confirmed by clinical examination, apnea tests, and electroencephalography. On the final day of hospitalization, the patient developed endotracheal bleeding with cardiovascular collapse and could not be resuscitated. This case highlights the fulminant course of invasive S. pyogenes infection in infants, particularly following varicella. These findings underscore the need for early recognition, aggressive management, and potential role of varicella vaccination in preventing secondary bacterial complications.