Nevin Manimala

Addiction. 2025 Nov 13. doi: 10.1111/add.70233. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: In recent years, the potency of natural cannabis products (herb and resin) has increased with a higher delta- 9-tetrahydrocannabinol (Δ9-THC) content, but there are limited data on trends on clinical presentation and severity of toxicity in cannabis users consulting the emergency department (ED) for acute intoxication. This study aimed to analyse the evolution over time of clinical findings and severity of presentations in a large series of patients presenting to European EDs with acute toxicity after lone cannabis use.

DESIGN: Secondary analysis of data included in the Euro-DEN Registry from 1 October 2013 to 31 December 2022.

SETTING: 40 EDs in 25 European countries.

PARTICIPANTS/CASES: ED presentations reporting lone cannabis use. Presentations reporting concomitant use of, or having positive toxicological tests for, ethanol or other drugs were excluded. 3839 ED presentations reporting lone cannabis use were analysed (median age 25 years, interquartile range= 20-33; 71% male).

MEASUREMENTS: Temporal trends of 14 pre-defined clinical signs/symptoms and 4 markers of severity, which included the need for ambulance transfer to the ED, hospitalisation, intensive care unit admission (ICU) and death.

FINDINGS: The most frequent clinical features were anxiety (35%), agitation (22%), decreased alertness (drowsiness or coma, 21%) and vomiting (20%), while seizures, arrythmias and hyperthermia were observed in <3% of cases. Statistically significant changes over time were only found in the frequency of hypotension [adjusted odds ratio (OR) = 1.239 per every subsequent year, 95% confidence interval (CI) = 1.107-1.386], hypertensive crisis (OR = 1.168, 95% CI = 1.070-1.274) and palpitations (OR = 0.922, 95% CI = 0.883-0.962). Nonlinear analyses detected statistically significant mid-period increases for anxiety, agitation and arrhythmias that subsided by the end of the study, and showed increases in chest pain and decreases in seizures that became statistically significant in the latter half of the period. Regarding episode severity, 76% of cases were brought to the ED by ambulance, 13% required hospitalisation, 1% were admitted to the ICU and 0.1% died. No statistically significant changes were observed over time in either the linear or the nonlinear models.

CONCLUSION: Very few changes in the clinical features of patients presenting to European emergency departments with lone acute cannabis toxicity were identified over 2013 to 2022, suggesting that despite the increase in potency of cannabis in Europe over this period, the severity of acute intoxication has remained unchanged.

PMID:41230681 | DOI:10.1111/add.70233

Eur J Psychotraumatol. 2025 Dec;16(1):2580210. doi: 10.1080/20008066.2025.2580210. Epub 2025 Nov 13.

ABSTRACT

Background: Complex post-traumatic stress disorder (cPTSD) was recently included in the ICD-11, extending the PTSD symptom profile to encompass disturbances in self-organization (DSO). Trauma-focused Dialectical Behavior Therapy (DBT-PTSD) is an effective psychotherapeutic treatment, particularly among women. However, empirical data on DBT-PTSD’s gender-specific effectiveness in naturalistic settings remains limited.Objective: The present study examined whether DBT-PTSD is similarly effective in reducing symptoms of cPTSD among women, men, and gender minority (GM) individuals under routine clinical conditions.Method: This observational single-center study included 215 patients (women = 78.1%, men = 18.6%, GM = 3.3%; 44.6+/-11.5 years) with cPTSD treated with DBT-PTSD at a psychosomatic inpatient clinic in Austria. Primary outcome was mean change in symptom severity assessed by the International Trauma Questionnaire (ITQ) before (T1) and after treatment (T2) and secondary assessment included anxiety and depression, somatization, dissociation, assessment of functioning, personality traits, emotion regulation, locus of control and borderline symptomatology. Repeated measures ANOVAs were used to evaluate treatment outcomes. Baseline predictors (T1) for ITQ score at T2 were identified by machine learning models and validated with mixed linear models.Results: While DBT-PTSD overall led to significant reductions in cPTSD symptoms with large effect size (p < .001, η² = 0.17), no significant difference was observed between men and women neither for the ITQ (p = .90, η² < 0.01), nor for any of the secondary outcomes (p = .08-.86; η² ≤ 0.01). Secondary outcomes showed statistically significant improvements in depression, anxiety, somatization emotion regulation and the locus of control (p < .001-.012). Higher negative affectivity was associated with worse outcomes in both men and women, while higher antagonism was associated with better outcomes in women and worse outcomes in men.Conclusions: DBT-PTSD is effective in reducing cPTSD symptoms among men and women in real-world clinical settings. However, larger samples of men are needed to validate the findings of this study.

PMID:41230649 | DOI:10.1080/20008066.2025.2580210

Leuk Lymphoma. 2025 Nov 13:1-9. doi: 10.1080/10428194.2025.2582732. Online ahead of print.

ABSTRACT

Adult histiocytic disorders are rare, and limited data exists on spectrum, clinical presentation and real-world management strategies. Here, we present Canadian single-center experience spanning over 23 years. Ninety-six patients were identified, with Langerhans Cell Histiocytosis (LCH; n = 60), Erdheim-Chester disease (ECD; n = 11); Rosai-Dorfman disease (RDD; n = 19) constituting the majority. At a median follow-up of 38 months, median OS of our cohort was not reached with encouraging 5-year OS of 96.3%, 79.5% and 86% amongst LCH, ECD and RDD patients respectively. Although, 5-year PFS rates were higher for LCH and RDD compared to ECD patients (61.7% vs 47% vs 24.2%; p = 0.320), these were not statistically significant. LCH patients with RO involvement had inferior 2-year PFS compared to those without (33.3% vs 75.8%; p = 0.042). A high incidence of concomitant hematological malignancies, (n = 3/11 in ECD and n = 3/60 in LCH) in our cohort warrants the need for further translational studies to explore possible association.

PMID:41230646 | DOI:10.1080/10428194.2025.2582732

Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2025 Sep 10;42(9):1069-1077. doi: 10.3760/cma.j.cn511374-20250303-00120.

ABSTRACT

OBJECTIVE: To explore the impact of age on the genetic variant spectrum and prognosis of patients with previously untreated Diffuse large B-cell lymphoma (DLBCL).

METHODS: A retrospective analysis was conducted on the clinical data and follow-up information of 254 previously untreated DLBCL patients from 14 hospitals in the Jiangsu Cooperative Lymphoma Group (JCLG) enrolled from July 2018 and July 2023. Following extraction of DNA from tumor tissue samples, next-generation sequencing (NGS) technique was employed to analyze the genetic variant spectrum of the DLBCL patients, with an evaluation of the relationship between age and genetic variants as well as prognosis. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Nantong University (Ethics No.: 2023-K048-01).

RESULTS: The median age of the 254 DLBCL patients was 62 years old, with 55% of patients aged 60 years or above. Clinical evaluation showed that younger (< 60 years) patients had higher complete response (CR) (70% vs. 59%), and objective response rate (ORR) (88% vs. 79%) than older patients, though the difference between the two groups was not statistically. Survival analysis indicated that both the five-year overall survival (OS) (82.7% vs. 71.7%, P = 0.006) and progression-free survival (PFS) (70.6% vs. 50.2%, P < 0.05) rates were significantly higher in younger patients. NGS showed that 99.6% of the patients harbored genetic variants, with PIM1, KMT2D, TP53, MYD88, and CD79B being the most common genes. Age significantly affected the variant frequency of certain genes, with MYC variants serving an adverse prognostic factor for OS in younger patients (P = 0.002), while TP53 (P = 0.024) and BCL2 (P = 0.002) variants significantly impacted OS in older patients. Prognostic analysis identified age ≥ 60 years (HR = 3.439, 95%CI: 1.318~9.874), presence of B symptoms (HR = 2.871, 95%CI = 1.133~7.307), and elevated lactate dehydrogenase (HR = 3.528, 95%CI = 1.231~10.66) as independent adverse prognostic factors.

CONCLUSION: Age, genetic variants, and clinical factors may significantly affect the prognosis of the DLBCL patients. Younger patients have better survival compared to older patients. Variants of the MYC, BCL2, and TP53 genes are closely associated with poor prognosis.

PMID:41230584 | DOI:10.3760/cma.j.cn511374-20250303-00120

Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2025 Sep 10;42(9):1039-1044. doi: 10.3760/cma.j.cn511374-20250326-00182.

ABSTRACT

OBJECTIVE: The haplotypes of Killer cell immunoglobulin-like receptors (KIR) can be divided into centromeric and telomeric ones. As the terminal gene at the centromeric end, KIR3DP1 plays an important role in stabilizing the haplotype structure. This study aimed to analyze the distribution of KIR3DP1 gene haplotypes among Han Chinese population in Zhejiang in order provide a basis for further analyzing the role of KIR3DP1 in the KIR haplotypes.

METHODS: A total of 166 unrelated blood donors from Zhejiang were collected (Blood donation period: March 2020 to August 2020), and genotyping was performed by next-generation sequencing based on exon capture. The copy number and allelic frequency of the KIR3DP1 gene and the distribution of centromeric haplotypes were statistically analyzed. This study was approved by the Medical Ethics Committee of Zhejiang Blood Center (Ethics No.: 2023-001).

RESULTS: The KIR3DP1 gene was positive for all individuals but with different copy numbers. Among these, 4 cases (2.4%) had only 1 copy, 156 cases (94.0%) had 2 copies, and 6 cases (3.6%) had 3 copies. A total of 10 KIR3DP1 alleles were found in the population, which could be classified into the KIR3DP1*001-L type, KIR3DP1*003-L type, and KIR3DP1 full deletion type. The KIR3DP1*003 L type allele was linked to the Cen-A01 and Cen-B01 types, and the KIR3DP1*001*L type allele and the KIR3DP1 deletion type were only present in the Cen-B02 type haplotype.

CONCLUSION: This study has derived a high-resolution distribution map of the KIR3DP1 gene in the Han population from Zhejiang, and found that the KIR3DP1 alleles showed different linkage with the centromeric haplotypes, which has provided a basis for further studying the role of KIR3DP1 in genetic immunity.

PMID:41230580 | DOI:10.3760/cma.j.cn511374-20250326-00182

Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2025 Sep 10;42(9):1033-1038. doi: 10.3760/cma.j.cn511374-20250707-00410.

ABSTRACT

OBJECTIVE: To explore the detection rate of copy number variations (CNVs) in fetuses with isolated Congenital anomalies of the kidney and urinary tract (CAKUT) and pregnancy outcomes in order to provide a basis for genetic counseling.

METHODS: One hundred and eighty eight fetuses who underwent chromosomal microarray analysis (CMA) due to isolated CAKUT detected by prenatal ultrasonography at Qingdao Women and Children’s Hospital from January 2021 to December 2024 were selected as the study subjects. According to the ultrasound findings, the fetuses were divided into 8 groups, including renal parenchymal dysplasia group, renal cystic dysplasia group, simple renal parenchymal echo enhancement group, abnormal development of renal collecting system group, duplicated kidney group, ectopic kidney group, horseshoe kidney group, and bladder/posterior urethral abnormalities group. The detection of CNVs was retrospectively analyzed, and the pregnant women were followed up to summarize their pregnancy outcomes. 2 test (or Fisher’s exact probability method) was used to compare the CNV detection rates between the groups. This study was approved by the Medical Ethics Committee of the Qingdao Women and Children’s Hospital (Ethics No.: QFELL-YJ-2025-85).

RESULTS: Among the 188 fetuses with isolated CAKUT, 23 CNVs (12.23%) were detected, of which 13 cases (6.91%) were pathogenic and 10 cases were rated as variants of unknown significance (VOUS). Among the 8 groups, the three groups with the highest proportion were renal cystic dysplasia group, renal metaplasia group, and renal parenchymal dysplasia group. The detection rates of pathogenic CNVs in the three groups were 1.79% (1/56), 6.78% (4/59), and 16.67% (5/30), respectively, with statistically significant differences (P < 0.05). Parental verification was conducted on 12 fetuses detected with the CNVs, confirming that 2 cases were de novo and 10 were inherited from parents with a normal phenotype. After genetic counseling, the parents of 9 fetuses opted to terminate the pregnancy, while 11 chose to continue with the pregnancy, and 3 were lost to follow-up. At the time of last follow-up, the youngest offspring was 5 months old and the oldest was 3 years and 11 months old. One child had renal aplasia, and two were born with hydronephrosis, which have been cured through surgery. The remainders had no obvious abnormality with their growth and development.

CONCLUSION: CMA testing has important value for prenatal diagnosis of isolated CAKUT. In this study, the detection rate of pathogenic CNVs has increased sequentially in fetuses with renal cystic developmental abnormalities, renal collecting system developmental abnormalities, and renal parenchymal dysplasia, while there was no significant difference in the detection rate of CNVs. For fetuses with isolated CAKUT detected by prenatal ultrasound, CMA testing should be considered, and reasonable pregnancy decisions should be made based on the results of prenatal ultrasound and parental verification.

PMID:41230579 | DOI:10.3760/cma.j.cn511374-20250707-00410

Langmuir. 2025 Nov 13. doi: 10.1021/acs.langmuir.5c02750. Online ahead of print.

ABSTRACT

Macroscopic properties of mesoporous metal oxides depend on the mesopore architecture, i.e., the pore size, wall thickness, and pore connectivity. Consequently, rational preparation protocols and deep knowledge of the templating mechanism are required for systematic porosity-property studies and the intentional synthesis of an optimized pore morphology. In this work, we thus prepared a library of 17 poly(ethylene oxide)-block-poly(hexyl acrylate) (PEO-b-PHA) block copolymers of varying PEO and PHA block lengths to quantitatively deduce the effect of the individual block lengths on the mesopore size of the templated silica. The block length of the hydrophobic PHA block in the micelle core showed to enable a pore size tuning between 10 and 80 nm according to electron microscopy, physisorption, and small-angle X-ray scattering. In contrast, varying the PEO block length did not alter the pore size, but revealed that a sufficiently large PEO block is required to ensure ordered spherical mesopores. Electron tomography confirmed a spherical pore geometry and a systematic decrease in pore wall thickness upon increasing the template concentration (i.e., template-to-silica ratio) during soft templating. A statistical in-depth analysis by tomography demonstrated that this wall size decrease is accompanied by an improved pore connectivity (e.g., in terms of the coordination number of adjacent pores) and an increasing pore size. The pore size increase originates from a partial PEO collapse on the micelle core based on a pore volume analysis and occurs only above a certain threshold concentration of block copolymer. We demonstrated that this concentration can be elevated by applying soft templates featuring shorter PEO blocks, which extend the regime of wall size tuning under preservation of pore dimension and shape. Overall, these insights provide a guideline on how to tailor the pore size, wall thickness, and pore connectivity of mesoporous metal oxides and enable systematic studies concerning the optimum porosity, e.g., for electrocatalytic applications to maximize stability and activity.

PMID:41230577 | DOI:10.1021/acs.langmuir.5c02750

Bio Protoc. 2025 Nov 5;15(21):e5491. doi: 10.21769/BioProtoc.5491. eCollection 2025 Nov 5.

ABSTRACT

Sheath blight, caused by Rhizoctonia solani, is a major fungal disease of rice that leads to significant yield losses globally. Conventional inoculation methods often fail to achieve consistent and uniform infection, limiting their applicability in antifungal screening studies. This protocol describes a reliable in planta inoculation method for R. solani using mature sclerotia placed at the internodal region of tillering-stage rice seedlings. The procedure includes step-by-step instructions for seed germination, seedling preparation, pathogen culture, artificial inoculation, and post-infection application of antifungal treatments, including botanical compounds such as Ocimum gratissimum essential oil and thymol. Lesion development is monitored and quantified over time, and data are analyzed statistically to evaluate treatment efficacy. The protocol is optimized for reproducibility, scalability, and compatibility with sustainable disease management approaches. It provides a robust platform for evaluating antifungal agents in a biologically relevant and controlled environment. Key features • Establishes a reliable in planta inoculation method for R. solani in rice, overcoming the common challenge of achieving consistent disease development. • Enables post-inoculation screening of botanicals for antifungal efficacy under realistic plant-pathogen interaction conditions. • Integrates sustainable research practices by detailing botanical extraction and their in planta assessment against R. solani infection.

PMID:41230549 | PMC:PMC12602175 | DOI:10.21769/BioProtoc.5491

Front Hum Neurosci. 2025 Oct 28;19:1652773. doi: 10.3389/fnhum.2025.1652773. eCollection 2025.

ABSTRACT

BACKGROUND: Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapidly progressive and fatal neurodegenerative disorder. Early diagnosis remains challenging due to nonspecific initial symptoms. Although electroencephalography (EEG) is a key diagnostic tool, particularly through the detection of periodic sharp wave complexes (PSWCs), the longitudinal evolution of EEG features and their correlation with clinical and neuroimaging progression are not fully characterized.

METHODS: This retrospective cohort study analyzed 37 patients diagnosed with probable and very probable sCJD according to the 2021 Chinese diagnostic guidelines. All patients underwent at least one EEG examination. One representative patient was followed for 23 weeks with serial EEG and MRI studies to document dynamic electrophysiological and structural changes. EEG background activity was graded as mild, moderate, or severe, and PSWCs were identified based on standardized criteria. MRI analyses focused on the spatial and temporal progression of hyperintense lesions on DWI and FLAIR sequences.

RESULTS: Among the 37 patients, 46% underwent initial EEG within 1 month of symptom onset, and 49% exhibited severe background abnormalities. PSWCs were present in 84% of patients at first EEG, with a high prevalence (82%) even in those examined within 4 weeks of onset. Longitudinal analysis in the index case revealed a progressive EEG deterioration: from slowed and disorganized background rhythms and emerging triphasic waves at 8 weeks, to widespread PSWCs with increasing periodicity (9-16 weeks), and finally to a burst-suppression pattern near electrical silence by week 23. Concurrent MRI showed a parallel expansion of hyperintense lesions from unilateral cortical and basal ganglia regions to bilateral involvement, closely correlated with the EEG progression. Statistical analysis showed no significant correlation between survival time and age, time to first EEG, CSF 14-3-3 protein status, or initial EEG background grade. Furthermore, neither the presence of typical PSWCs nor the severity of background activity was associated with survival outcomes.

CONCLUSION: EEG, especially the early and highly prevalent presence of PSWCs, offers high diagnostic value in sCJD but does not serve as prognostic predictors. The close correlation between EEG decline and MRI progression supports multimodal monitoring. Serial EEG should be integrated into sCJD diagnosis and follow-up.

PMID:41230545 | PMC:PMC12602467 | DOI:10.3389/fnhum.2025.1652773

J R Stat Soc Series B Stat Methodol. 2025 May 27;87(5):1508-1527. doi: 10.1093/jrsssb/qkaf028. eCollection 2025 Nov.

ABSTRACT

When an exposure of interest is confounded by unmeasured factors, an instrumental variable (IV) can be used to identify and estimate certain causal contrasts. Identification of the marginal average treatment effect (ATE) from IVs relies on strong untestable structural assumptions. When one is unwilling to assert such structure, IVs can nonetheless be used to construct bounds on the ATE. Famously, Alexander Balke and Judea Pearl proved tight bounds on the ATE for a binary outcome, in a randomized trial with noncompliance and no covariate information. We demonstrate how these bounds remain useful in observational settings with baseline confounders of the IV, as well as randomized trials with measured baseline covariates. The resulting bounds on the ATE are nonsmooth functionals, and thus standard nonparametric efficiency theory is not immediately applicable. To remedy this, we propose (1) under a novel margin condition, influence function-based estimators of the bounds that can attain parametric convergence rates when the nuisance functions are modelled flexibly, and (2) estimators of smooth approximations of these bounds. We propose extensions to continuous outcomes, explore finite sample properties in simulations, and illustrate the proposed estimators in an observational study targeting the effect of higher education on wages.

PMID:41230541 | PMC:PMC12602419 | DOI:10.1093/jrsssb/qkaf028