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Background and Objectives: Mitochondrial disorders are multiorgan disorders resulting in significant morbidity and mortality. We aimed to characterize death-associated factors in an international cohort of deceased individuals with mitochondrial disorders., Methods: This cross-sectional multicenter observational study used data provided by 26 mitochondrial disease centers from 8 countries from January 2022 to March 2023. Individuals with genetically confirmed mitochondrial disorders were included, along with patients with clinically or genetically diagnosed Leigh syndrome. Collected data included demographic and genetic diagnosis variables, clinical phenotype, involvement of organs and systems, conditions leading to death, and supportive care. We defined pediatric and adult groups based on age at death before or after 18 years, respectively. We used Kruskal-Wallis with post hoc Dunn test with Bonferroni correction and Fisher exact test for comparisons, Spearman rank test for correlations, and multiple linear regression for multivariable analysis., Results: Data from 330 deceased individuals with mitochondrial disorders (191 [57.9%] pediatric) were analyzed. The shortest survival times were observed in hepatocerebral syndrome (median 0.3, interquartile range [IQR] 0.2-0.6 years) and mitochondrial cardiomyopathy (median 0.3, IQR 0.2-5.2 years) and the longest in chronic progressive external ophthalmoplegia plus (median 26.5, IQR 22.8-40.2 years) and sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (median 21.0, IQR 13.8-28.5 years). Respiratory failure and pulmonary infections were the most common conditions associated with death (52/330, 15.7% and 46/330, 13.9%, respectively). Noninvasive ventilation was required more often in children (57/191, 29.8%) than adults (12/139, 8.6%, p < 0.001), as was nasogastric or gastric tube (131/191, 68.6% in children and 39/139, 28.1% in adults, p < 0.001). On multivariate analysis, individuals with movement disorders and nuclear gene involvement had increased odds of any respiratory support use (OR 2.42 (95% CI 1.17-5.22) and OR 2.39 (95% CI 1.16-5.07), respectively)., Discussion: This international collaboration highlights the importance of respiratory care and infection management and provides a reference for prognostication across different mitochondrial disorders.

Meaning-based interventions have demonstrated promising outcomes in enhancing meaning in life. However, understanding their efficacy in diverse contexts requires further research. This study aims to investigate the effectiveness of a meaning-based intervention in a military sample and the impact of incorporating an additional emotion regulation module into the intervention. We conducted a randomized three-group parallel trial with active-duty military personnel: a waitlist control group (n = 21), a meaning-based intervention group (n = 42), and a meaning-based intervention with emotion regulation group (n = 43). Both intervention groups received six 2-hour sessions and a follow-up session 4 months later. Meaning in life and work-related variables, as well as well-being, depression, emotion regulation, and work-related factors, were assessed using a mixed-factorial analysis of variance (ANOVA). The results showed that only the meaning-based intervention with an emotion regulation component significantly increased the presence of meaning in life. We also observed a trend toward improved well-being scores over time that did not emerge for the other intervention. This study provides initial support for the efficacy of meaning-based interventions within the military context when supplemented with emotion regulation skills., (© 2024 The Author(s). Applied Psychology: Health and Well‐Being published by John Wiley & Sons Ltd on behalf of International Association of Applied Psychology.)

Although proteins in snake venoms have been extensively studied and characterized, low-mass molecules remain relatively unexplored, mainly due to their low abundance, secondary role in envenomation, and some analytical technique limitations. However, these small molecules can provide new important data related to venom toxins' molecular structure, functions, and evolutionary relationships. This research aimed to characterize molecules below 10 kDa in the venoms of snakes from the Viperidae families (Bothrops, Agkistrodon, and Bitis) and compare two chromatographic approaches: reverse-phase chromatography (RP), a classic technique, and hydrophilic interaction liquid chromatography (HILIC), an alternative technique, both coupled with high-resolution mass spectrometry (HRMS). The results showed that the separation of the HILIC column provided a more efficient evenly distributed ion profile than RP, contributing to a 25.6% increase in the sequences identified. Homologous sequences for Bradykinin-potentiating peptides (BPPs) and fragments of major venom proteins, possibly cryptids, were found. In addition, BPP 13a, peptides rich in histidine and glycine (pHpG), and spacer sequences were identified in all snakes analyzed, especially with HILIC separation, suggesting that these sequences may be conserved within Viperidae. These findings indicate that the use of the HILIC column, compared to RP, is a promising approach for characterizing peptides in snake venom obtained by the ultrafiltration process. It contributes to the study of these still poorly understood molecules and is also a good option for studying other complex protein/peptide mixtures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Trypanosomatidae diseases, such as Chagas disease and leishmaniasis, are caused by protozoan parasites of the Trypanosomatidae family, namely Trypanosoma cruzi and Leishmania species, respectively. There is an urgent need for new therapies. Both pyridine and thiazole rings are recognized as important scaffolds in medicinal chemistry. This study reports the synthesis of 3-pyridyl-1,3-thiazole derivatives (1-18) and their evaluation through in vitro and in vivo assays. In vitro tests were conducted against T. cruzi, L. amazonensis, and L. infantum, with cytotoxicity assessed using L929 fibroblasts and RAW 264.7 macrophages. Mode of action studies included in vitro assays and in silico simulations. Fourteen compounds exhibited trypanocidal activity with IC 50 values ranging from 0.2 to 3.9 μM, outperforming benznidazole (4.2 μM). Compound 7 displayed an IC 50 of 0.4 μM and a selectivity index of 530.8. However, the compounds were inactive in vivo assays at a dose of 100 mg/kg/day. Compounds 1, 7, 8, and 10 demonstrated trypanostatic effects, mitochondrial disruption, apoptosis induction, and parasite membrane damage. These compounds also modulated nitric oxide, IL-6, IL-10 and TNF production. In silico analysis indicated strong interactions with cruzain and favorable bioavailability, drug-likeness, and stability profiles. The leishmanicidal activity was negligible or absent. Despite promising in vitro trypanocidal activity, further structural optimization or formulation strategies are required to enhance oral stability and bioavailability, providing a foundation for the development of new therapeutic agents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Masson SAS. All rights reserved.)

Ferroptosis, a form of regulated cell death, is characterized by iron-dependent lipid peroxidation. It is recognized increasingly for its pivotal role in both cancer development and the response to cancer treatments. We assessed associations between 370,027 single-nucleotide polymorphisms (SNPs) within 467 ferroptosis-related genes and survival of non-small cell lung cancer (NSCLC) patients. Data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial served as our discovery dataset, while the Harvard Lung Cancer Susceptibility Study used as our validation dataset. For SNPs that remained statistically significantly associated with overall survival (OS) in both datasets, we employed a multivariable stepwise Cox proportional hazards regression model with the PLCO dataset. Ultimately, two independent SNPs, PARK7 rs225120 C>T and DDR2 rs881127 T>C, were identified with adjusted hazard ratios of 1.32 (95% confidence interval = 1.15-1.52, p = .0001) and 1.34 (95% confidence interval = 1.09-1.64, p = .006) for OS, respectively. We aggregated these two SNPs into a genetic score reflecting the number of unfavorable genotypes (NUG) in further multivariable analysis, revealing a noteworthy association between increased NUG and diminished OS (p trend  = .001). Additionally, an expression quantitative trait loci analysis indicated that PARK7 rs225120T genotypes were significantly associated with higher PARK7 mRNA expression levels in both whole blood and normal lung tissue. Conversely, DDR2 rs881127C genotypes were significantly associated with lower DDR2 mRNA expression levels in normal lung tissue. Our findings suggest that genetic variants in the ferroptosis-related genes PARK7 and DDR2 are associated with NSCLC survival, potentially through their influence on gene expression levels., (© 2024 UICC.)

Screening plays a crucial role in the early detection of colorectal cancer, greatly reducing mortality rates. The objective of this study was to identify a non-invasive diagnostic method utilizing serum microRNA expression for the diagnosis of colorectal cancer patients. The study consisted of three stages. In the first stage, 129 patients with colorectal cancer and 129 normal subjects were recruited as the training set for the development of a blood miRNA panel. The second stage involved recruiting 200 patients from each group as the validation cohort. Finally, a blinded study was conducted in the third stage, with 260 patients recruited to determine the predictive value of our miRNA panel. Serum samples were prospectively collected from colorectal cancer patients and normal subjects between 2017 and 2021 at Queen Mary Hospital in Hong Kong. Quantitative PCR was utilized to detect the serum levels of candidate microRNAs, and a multiple linear regression model was employed to formulate a serum microRNA panel for diagnosing colorectal cancer patients. The performance of the panel was evaluated using ROC analysis. Our study showed that the values of three pairs of serum microRNAs, namely miR-106b-5p/miR-1246, miR-106b-5p/miR-16 and miR-106b-5p/miR-21-5p, exhibited statistically significant differences between colorectal cancer patients and normal subjects. A serum microRNA panel formulated from these three pairs of microRNAs demonstrated high accuracy in diagnosing colorectal cancer patients from normal subjects, with an AUC of approximately 0.9. The serum miRNA test proved to be a feasible and promising non-invasive biomarker for the diagnosis of colorectal cancer patients in comparison to normal subjects., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Bovine whey contains bioactive proteins that could benefit consumer health, but their intact bioactivity depends on their ability to survive the digestive process and remain intact to their sites of action. Our study assessed whey protein degradation in the adult human jejunum after whey protein isolate ingestion and during static in vitro gastric and intestinal digestions, using LC-MS/MS-based proteomics and SDS-PAGE. We found that 53 % of the protein counts identified in the gastric digesta, including β-lactoglobulin and lactoferrin were stable under simulated gastric conditions. However, most proteins were degraded during both in vitro and in vivo intestinal digestion. The intact protein survival profiles were closely aligned between in vitro and in vivo digestion samples. Understanding the survival of specific whey proteins during digestion will help determine their biological relevancy in their intact forms within the gastrointestinal tract and may inspire strategies to enhance their stability for specific functions., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: David Dallas reports financial support was provided by BUILD Dairy. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Intravenous tenecteplase (TNK) is increasingly used to treat adult patients with acute arterial ischemic stroke, but the risk profile of TNK in childhood stroke is unknown. This study aims to prospectively gather safety data regarding TNK administration in children., Methods: Since December 2023, a monthly email survey was sent to participants recruited from the International Pediatric Stroke Study and Pediatric Neurocritical Care Research Group querying recent experience with TNK in childhood stroke. Limited demographic, safety, and outcome data were collected in a secure REDCap database. Detailed clinical data were not collected., Results: Eleven children were reported to have received TNK between February 2023 and January 2024. Ten were adolescents (13-17 years old), and 1 was between 5 and 12 years old. TNK was given at an outside facility before transfer to the reporting facility in 7 cases. Final diagnosis was stroke in 8 cases and stroke mimic in 3 cases. No major safety concerns or TNK-related intracranial hemorrhages on follow-up imaging were reported., Discussion: Our initial data suggest that TNK may be safe in childhood arterial ischemic stroke. Strategically designed prospective studies are needed to further define safety, optimal dosage, and efficacy of TNK in acute pediatric stroke.

Ethnopharmacological Relevance: Anxiety and depression are leading causes of disability worldwide, often exacerbated by chronic stress. Schinus terebinthifolia Raddi. has been used in traditional medicine for several purposes. Among these, the use of bark-and-leaf tea and leaf decoction to treat depression has been reported. Previous studies showed that the S. terebinthifolia leaf lectin (SteLL) can ameliorate anxiety and depression symptoms in mice., Aim of the Study: To investigate SteLL as a compound from S. terebinthifolia leaf able to alleviate symptoms of depression and anxiety in an unpredictable chronic mild stress (UCMS) animal model., Methods: Mice were subjected to four-week UCMS and then treated with SteLL at 2 and 4 mg/kg (i.p.) or with fluoxetine at 10 mg/kg i.p. (positive control) for 21 days. Behavioral assessments were conducted using the open field test, elevated plus maze, tail suspension test, and sucrose preference test. Serum corticosterone and inflammatory markers (cytokines) levels were determined. The levels of cytokine, oxidative stress indicators and monoamines in brain homogenates were also measured to understand the biochemical changes induced by SteLL treatment., Results: SteLL treatment at both doses significantly (p < 0.05) alleviated the stress-induced behavior in mice, reducing the anxiety and depression signals in all tests. SteLL administration increased the brain levels of monoamines noradrenaline and serotonin in comparison with UCMS control mice that received only vehicle. SteLL reduced superoxide production, lipid peroxidation and improved reduced glutathione (GSH) levels in the brain. The lectin also increased serum and brain levels of anti-inflammatory cytokine IL-4, while reducing levels of pro-inflammatory cytokines. Serum corticosterone levels were not decreased by lectin treatment., Conclusion: Our findings highlight SteLL as a neuromodulatory agent from S. terebinthifolia leaves effective in subacute and stress-induced anxiety and depression through modulation of monoaminergic, oxidative stress, and inflammatory pathways. The data shows the potential of this lectin as a therapeutic agent for stress-related neuropsychological disorders., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Objectives: To analyze sex differences in outcomes in Tourette syndrome (TS) and Persistent Motor or Vocal tic disorders (PMVT) in the Tourette Association of America International Consortium for Genetics (TAAICG) dataset., Methods: The relationship between sex and clinical measures was explored in 2,403 participants (N = 2,109 with TS; N = 294 with PMVT) from the TAAICG dataset using generalized estimating equation regression models, and adjusted for age and family relationships., Results: Female (vs male) participants with TS (25.5% of the sample) had 0.46 times lower odds of being formally diagnosed clinically with TS before the research study ( p < 0.00001), later age at symptom onset (6.5 ± 2.8 vs 6.0 ± 2.7; p = 0.001), later age at diagnosis (13.3 ± 11.2 vs 10.7 ± 8.1; p = 0.0001), a longer time-to-diagnosis (3 [1, 7] vs 2 [1, 5], p = 0.01), and lower tic severity (28.4 ± 9.1 vs 30.7 ± 8.7); p < 0.0001). Female (vs male) participants with PMVT (42.9% of the sample) had an earlier age at symptom onset (7.9 ± 3.3 vs 8.9 ± 3.7; p = 0.05)., Discussion: Female (vs male) participants with TS are less likely to be formally diagnosed, have later age at symptom onset, later age at diagnosis, and longer time-to-diagnosis. Female (vs male) participants with PMVT have an earlier age at symptom onset. Future research is needed to understand differences longitudinally in TS and PMVT.

Abstract: Variances in global access to drugs and treatment practices make it challenging to understand the benefit of contemporary therapies in patients with relapsed and refractory (R/R) mature T-cell and natural killer-cell lymphomas (MTCL and MNKCL). We conducted an international retrospective cohort study of 925 patients with R/R MTCL and MNKCL. In peripheral T-cell lymphoma-not otherwise specified and anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (ALK- ALCL), patients with relapsed lymphoma demonstrated a superior median overall survival (OS) relative to refractory from the time of second-line treatment. We identified several independent predictors of OS for R/R lymphoma including age >60 years, primary refractory disease, histological subtype other than angioimmunoblastic T-cell lymphoma (AITL), extranodal sites >1, Ki67 ≥40%, and absolute lymphocyte count less than the lower limit of normal. A multivariable model incorporating these formed the basis for a prognostic index for R/R TCL, in which patients are stratified into low-risk (0-1 risk factor), intermediate-risk (2-3 risk factors), or high-risk (≥4 risk factors) groups, which were associated with 3-year OS of 57.14%, 23.3%, and 7%, respectively. Patients received either a "novel" single agent (SA; 35%) or cytotoxic chemotherapy (CC; 60%) for their second-line treatment. Higher progression-free survival was observed with SA over CC for the entire cohort with a higher 3-year OS in AITL and ALK- ALCL. Among the SA, small-molecule inhibitors demonstrated OS advantage relative to CC in AITL. Our results highlight continued efficacy of novel drugs globally and the potential of a new prediction model in informing heterogeneous prognosis within the R/R population of MTCL and MNKCL., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Abstract: Lisocabtagene maraleucel (liso-cel) and axicabtagene ciloleucel (axi-cel) are anti-CD19 chimeric antigen receptor (CAR) T-cell therapies approved for relapsed and refractory large B-cell lymphoma (LBCL); however, there is currently no published data on liso-cel outside of clinical trials nor any data comparing these therapies. In this retrospective analysis, we reviewed patients with LBCL receiving liso-cel or axi-cel at a single institution in the third-line setting. From June 2021 to September 2022, a total of 50 patients received axi-cel and 37 liso-cel. Baseline patient characteristics were similar, aside from older age in liso-cel recipients. The median time from leukapheresis to CAR T-cell infusion was significantly longer for liso-cel (41 days) than axi-cel (30 days). Complete response rates were not significantly different between axi-cel (72%) and liso-cel (62%). At a median follow-up of 11 months, progression-free survival (PFS) was not significantly different between axi-cel and liso-cel cohorts, with 12-month PFS of 59% and 44%, respectively. However, on a propensity score analysis, an inferior PFS was observed with liso-cel (hazard ratio, 2.95; 95% confidence interval , 1.14-7.60). The rates of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and prolonged neutropenia were higher with axi-cel than liso-cel. Overall, direct comparison of axi-cel and liso-cel cohorts shows similar key outcomes including response rate and PFS, but prolonged wait times for liso-cel may have resulted in biased selection of patients with more favorable characteristics for liso-cel. When accounting for these higher-risk characteristics, an inferior PFS is observed with liso-cel compared with axi-cel. These findings warrant further evaluation in a multicenter setting., (© 2025 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Objectives: Moyamoya disease (MMD) is a rare cerebrovascular condition, and it is a well-known risk factor of acute ischemic stroke (AIS). While IV thrombolysis (IVT) is an established treatment for patients with AIS, its efficacy and safety for patients with MMD is largely unknown., Methods: This was a large retrospective analysis of the 2016-2021 Nationwide Readmissions Database in the United States. MMD patients with AIS were included. Patients who underwent bypass surgery were excluded. Propensity score matching (PSM) was performed to match IVT patients with similar patients who were managed conservatively. The primary efficacy outcome was routine discharge to home with self-care. Safety outcomes included intracranial hemorrhage (ICH) and in-hospital mortality., Results: A total of 3,050 MMD patients with AIS were identified, of whom 214 (7.0%) were treated with IVT. After PSM, IVT patients had higher rates of routine discharge compared with those who were not treated with IVT (53.6% vs 45.1%, respectively, p = 0.045). IVT treatment, compared with no-IVT, was not associated with different rates of ICH (7.1% vs 10.9%, p = 0.58) or in-hospital mortality (3.8% vs 5.3%, p = 0.93)., Discussion: IVT is seldom used to treat AIS in patients with MMD, and it may be effective and safe for select cases. Confirmation with prospective studies is needed.

The complement system plays a crucial role in various pathophysiological conditions, including snake envenomation. In this study, we investigated the effects of Bitis arietans venom on the complement system using an ex vivo human whole blood model. Our findings demonstrate that B. arietans venom was able to activate the complement system, leading to a significant increase in the production of anaphylatoxins (C3a/C3a-desArg, C5a/C5a-desArg) and the soluble Terminal Complement Complex (sTCC). Inhibition of the C3 component by Cp40, a C3-C3b inhibitor, resulted in the reduction of C3a/C3a-desArg, C5a/C5a-desArg, and sTCC levels to baseline in venom-stimulated samples. Furthermore, treatment with Cp40 promoted a substantial decrease in the production of pro-inflammatory mediators, such as Prostaglandin E 2 (PGE 2 ), IL-8/CXCL8, MCP-1/CCL2, and MIG/CXCL9. To further elucidate the molecular mechanisms, we utilized the THP-1 cell line differentiated into M0 macrophages. Incubation of these macrophages with human plasma, from the human whole blood treated with B. arietans venom, resulted in the expression of the NLRP3 inflammasome and the production of IL-8 and IL-1β. Importantly, Cp40 was able to diminish the production of these cytokines, as well as the levels of ASC and caspase-1 proteins. In conclusion, our results indicate that the inhibition of the complement by Cp40 at C3/C3b level can modulate the inflammatory response and inflammasome activation induced by B. arietans venom. These findings suggest that complement inhibition may be a promising therapeutic approach for managing the inflammatory complications associated with this snake envenomation., Competing Interests: Declaration of competing interest JDL is the founder of Amyndas Pharmaceuticals, which develops complement inhibitors for therapeutic purposes; is inventor of a broad patent portfolio that describes the therapeutic use of complement inhibitors, some of which are developed by Amyndas Pharmaceuticals, inventor of the compstatin technology licensed to Apellis Pharmaceuticals i.e., 41MeW7W/POT-4/APL-1 and pegylated derivatives such as APL-2/ pegcetacoplan and APL-9., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A new sensor based on Ethylbenzothiazolium-2-hydroxynaphthaldehyde conjugate-based fluorescent sensor, (E)-3-ethyl-2-(2-(2-hydroxynaphthalen-1-yl) vinyl) benzo[d]thiazol-3-ium iodide (SU-1) was designed and synthesized. The structure of SU-1 was confirmed by 1 H NMR, 13 C NMR, HRMS, and single crystal XRD spectral analysis. SU-1 displayed a colorimetric and fluorometric response in a DMSO:H 2 O (1:1,v/v) matrix, changing color from pale yellow to colorless visible to the naked eye, accompanied by a ∼ 120 nm red-shift in the absorption spectra upon CN - addition. This shift, due to formation of deprotonation followed by the nucleophilic attack on the benzothiazolium ring's double bond, disrupts π-conjugation, blocking intramolecular charge transfer within SU-1. However, competitive anions showed negligible interference while detecting CN - . The Limit of detection for CN - was determined to be 0.27 nM, significantly below the WHO's permissible CN - concentration in drinking water (1.9 μM). Job's plot analysis shows that the binding stoichiometry of SU-1 to CN - is a 1:1, with a stability constant (Ka) of 1.58 x 10 4 M -1 . The sensor demonstrated practical applications in environmental water samples and fluorescence imaging of intracellular CN - in CAD cell line., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Phyto-based treatments for anxiety and depression are gaining attention. The efficacy of the water-soluble Moringa oleifera seed lectin (WSMoL) in reducing acute anxiolytic and depressive-like behaviors in mice has been previously demonstrated. In the present study, it was evaluated the effects of WSMoL on reducing anxiety and depressive-like symptoms in a mouse model of unpredictable chronic mild stress (UCMS). The animals were divided into groups and exposed to a four-week UCMS regimen. Following this, the mice received daily intraperitoneal injections of vehicle (non-stressed and UCMS control groups), WSMoL (2 or 4 mg/kg), or fluoxetine (10 mg/kg) for 21 days. Neurobehavioral tests included the open field test and elevated plus maze test to assess anxiety-like behavior, and the tail suspension test and sucrose preference test to evaluate depression-like behavior. Biochemical analyses measured serum corticosterone and cytokines as well brain levels of cytokines and monoamines. All tests indicated that WSMoL significantly (p < 0.05) reversed the anxiety and depression-like behaviors induced by UCMS. The stress protocol increased serum corticosterone levels and WSMoL treatment was not able to normalize corticosterone secretion. WSMoL treatment reduced serum and brain levels of IL-2, IL-6, and TNF-α, indicating reduced neuroinflammation, and increased brain levels of dopamine, serotonin, and noradrenaline. In summary, WSMoL mitigated UCMS-induced anxiety and depression-like behaviors by reducing neuroinflammation and modulating brain monoamine levels., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Cardiologists are increasingly moving from independent practice to direct employment by hospitals. Hospital employment has the potential to improve care coordination and delivery, but little is known about its effect on care quality and outcomes., Objectives: In this study, we sought to assess the association between hospital employment of cardiologists and patient outcomes, care quality, and utilization among patients hospitalized with incident acute myocardial infarction (AMI) or heart failure (HF)., Methods: We used a sample of Medicare fee-for-service beneficiaries hospitalized with incident AMI or HF from 2008 to 2019. We identified the accountable cardiologists that cared for these patients and determined their employment status by means of tax identification numbers. We used difference-in-differences methods to compare clinical outcomes, quality measures, and utilization for patients treated by hospital-employed cardiologists after switching from independent to hospital-employed practice, to outcomes for patients treated by cardiologists who remained independent. Models were adjusted for time trends and patient, hospital, and cardiologist characteristics. Patient outcomes were in-hospital mortality, 30-day mortality, and 30-day readmission. Quality measures were receipt of: 1) a guideline-recommended test to assess cardiac function; and 2) a 30-day follow-up clinic visit. Utilization measures were length of stay and, for AMI patients, the proportion receiving coronary revascularization., Results: The proportion of U.S. cardiologists employed by hospitals increased from 26% in 2008 to 63% in 2019. We identified 186,052 AMI and 259,849 HF patients cared for by cardiologists who switched to hospital employment and 168,052 AMI and 245,769 HF patients cared for by independent cardiologists. Patient characteristics were similar (mean age 80.8 years; 47% men). We found no significant differences in outcomes (eg, adjusted difference in 30-day mortality 0.03% [95% CI: -0.39% to 0.45%] for AMI patients and -0.05% [95% CI: -0.37% to 0.27%] for HF patients); no differences in most quality metrics except a small increase in the proportion of HF patients with 30-day follow-up (adjusted difference: 1.04%; 95% CI: 0.46%-1.62%); and no differences in utilization between patients treated by hospital-employed cardiologists (postswitch) vs independent cardiologists., Conclusions: Among U.S. cardiologists, there has been a large shift from independent practice to direct employment by hospitals. We found minimal evidence that cardiologist employment by hospitals improves care quality or outcomes., Competing Interests: Funding Support and Author Disclosures This study was supported by funding from the National Heart, Lung, and Blood Institute, National Institutes of Health (R01HL153154). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: 1) To discontinue gradually the current non-probabilistic equivalent dose (E) methodology in the radiation protection (RP) with our proposed E0(HN) one; HN is H set of all tissue or organs (ToOs) irradiated. E0 is directly associated with probability of non-harmful effects of low levels of ionizing radiation; 2) To apply the radiation oncology normal tissue non-complication probability (NTCP0) methodology for evaluations in other radiation activity (RAs); and 3) To apply the SMp(x) function in the graphical models of UNSCEAR in order to a) To establish the lower limit of the 100%-risk deterministic region, i.e. 0%-safety deterministic one; b) To correct the representation of the "Hormetic" model; and c) To express with mathematical formulas these models. The two first aspects will represent corrections for these graphical models., Methods: Radiobiological-probabilistic studies aimed to represent the stochastic health safety to the ToOs using NTCP0 and E0 as inherent probabilistic concepts., Conclusion: The E0 methodology will represent to eliminate gradually the current E one, Sv, rem and expressing equivalent dose (H) in Gy. This study will push: 1) Improvements over the UNSCEAR graphical models; and 2) To extend to all RAs the NTCP0 methodology.

Background: QT correction (QTc) formulae are widely used in clinical and research settings but often underperform, possibly due to demographic influences on the QT-heart rate (HR) relationship. To address this limitation, we developed an adaptive QTc (QTcAd) formula, which adjusts for demographic factors like age, and compared its efficacy to other standard formulae., Methods: The QTcAd formula was tested across diverse age groups with different HR in both humans and guinea pigs. Using retrospective ECG data from 1819 pediatric patients at Children's National Hospital and 2400 subjects from the Pediatric Heart Network database, alongside in vivo (n=55) and ex vivo (n=66) guinea pig ECG recordings, we evaluated the formula's effectiveness. Linear regression fit parameters of QTc-HR (slope and R ²) were utilized for performance assessment. To evaluate the accuracy of the predicted QTc, we acquired epicardial electrical and optical voltage data from Langendorff-perfused guinea pig hearts., Results: In both human subjects and guinea pigs, the QTcAd formula (QTcAd=QT+(| m |×(HR-HR mean )) consistently outperformed other formulae across all age groups. For instance, in a 20-year-old human group, the QTcAd formula successfully nullified the inverse QT-HR relationship ( R ²=5.1×10 - 10 , slope=-3.5×10 - 5 ), whereas the Bazett formula failed to achieve comparable effectiveness ( R ²=0.21, slope=0.91). Moreover, the QTcAd formula exhibited better accuracy than the age-specific Benatar QTc formula, which overcorrected QTc (1-week human QT: 263.8±14.8 ms, QTcAd: 263.8±7.3 ms, P =0.62; Benatar QTc: 422.5±7.3 ms, P <0.0001). The optically measured pseudo-QT interval (143±22.5 ms, n=44) was better approximated by QTcAd (180.6±17.0 ms) compared with all other formulae. Furthermore, we demonstrated that the QTcAd formula was not inferior to individual-specific QTc formulae., Conclusions: The demography-based QTcAd formula showed superior performance across human and guinea pig age groups, which may enhance the efficacy of rate-corrected QTc for cardiovascular disease diagnosis, risk stratification, and drug safety testing in children and adults.

Background: Infants with congenital heart disease require early lifesaving heart surgery, which increases risk for brain injury and neurodevelopmental delay. Cerebral microhemorrhages (CMH) are frequently seen after surgery, but whether they are benign or constitute injury is unknown., Methods and Results: One hundred ninety-two infants with congenital heart disease undergoing cardiac surgery with cardiopulmonary bypass were evaluated with pre- (n=183) and/or postoperative (n=162) magnetic resonance imaging. Perioperative risk factors for CMH and neurodevelopmental outcomes were analyzed using linear regression. Eighteen-month neurodevelopmental outcomes were assessed in a subset of patients (n=82). The most common congenital heart disease subtypes were hypoplastic left heart syndrome (37%) and transposition of the great arteries (33%). Forty-two infants (23%) had CMH present on magnetic resonance imaging presurgery and 137 infants (85%) postsurgery. We found no significant risk factors for preoperative CMH. In multivariable analysis, neurodevelopmental duration ( P <0.0001), use of extracorporeal membrane oxygenation support ( P <0.0005), postoperative seizure(s) ( P =0.02), and lower birth weight ( P =0.03) were associated with new or worsened CMH postoperatively. A higher CMH number was associated with lower motor scores ( P =0.01) at 18 months., Conclusions: CMH are common imaging findings in infants with congenital heart disease, particularly after cardiopulmonary bypass conferring adverse impact on neurodevelopmental outcomes at 18 months. Longer duration of cardiopulmonary bypass and extracorporeal membrane oxygenation use demonstrated greatest risk for developing CMH. However, the presence of CMH on preoperative scans indicates yet unidentified nonperioperative risk factors. Neuroprotective strategies to mitigate CMH risk may improve neurodevelopmental outcomes in this vulnerable population.

Background: Coronary microvascular dysfunction (CMD), which mimics symptoms of obstructive coronary artery disease, has significant prognostic implications. While epicardial adipose tissue normally has a protective role, increased epicardial adipose tissue is associated with inflammation and may contribute to CMD. However, a direct correlation remains unclear. We aimed to investigate this association., Methods and Results: The CMDR (Coronary Microvascular Disease Registry) is a prospective, 2-center registry that is enrolling patients with angina and nonobstructive coronary artery disease who underwent invasive hemodynamic assessment of the coronary microvasculature. Patients with chest computed tomography within 1 year of CMD evaluation were included. We measured epicardial fat volume (EFV) and calculated the EFV index. Logistic regression analysis was used to investigate the association between EFV and EFV index to CMD. Our study included 130 CMDR patients with associated chest CT; 35 were diagnosed with CMD. The CMD-negative patients were younger than the CMD-positive patients (58.52±11.97 versus 63.37±9.56 years; P =0.033), with numerically fewer women (64.2% versus 74.3%; P =0.279). Univariate regression analysis demonstrated a statistically significant association between EFV index and CMD diagnosis (odds ratio, 1.037 [95% CI, 1.014-1.063]; P =0.003), while no significance was observed for EFV (odds ratio, 1.006 [95% CI, 0.995-1.017]; P =0.292)., Conclusions: Our results suggest a strong association between EFV index (a significant risk factor) and the presence of CMD. Future studies involving larger cohorts are needed to confirm the association of epicardial adipose tissue with CMD and investigate therapeutic targets to prevent CMD., Registration: URL: https://www.clinicaltrials.gov; unique identifier: NCT05960474.

Stimulant use disorder (StUD) is a rapidly growing concern in the United States, with escalating rates of death attributed to amphetamines and cocaine. No medications are currently approved for StUD treatment, leaving clinicians to navigate off-label medication options. Recent studies suggest that controlled prescription psychostimulants such as dextroamphetamine, methylphenidate, and modafinil are associated with reductions in self-reported stimulant use, craving, and depressive symptoms. Despite this positive initial evidence, prescribing rates of these medications for StUD treatment remain low, possibly because some clinicians believe that they are subject to the restrictions federal law imposes on medications for opioid use disorder. This is not the case. Rather, at the federal level, these medications are subject only to the general requirement that prescriptions be issued for a legitimate medical purpose within the usual course of professional practice, criteria that are buttressed by recent national guidelines that include controlled prescription psychostimulants as an option within a comprehensive treatment plan for StUD. In this commentary, we review the federal legal landscape regarding the prescription of psychostimulants for StUD and recommend strategies for increasing the utilization of this promising approach. Professional organizations, addiction clinicians, and researchers can reinforce this practice through publishing expert recommendations, developing clinician education materials, and disseminating their real-world experiences and well-documented treatment plans., Competing Interests: The authors report no conflicts of interest., (Copyright © 2025 American Society of Addiction Medicine.)

Metabolic dysfunction-associated steatohepatitis (MASH) has become the dominant cause of liver disease in the United States. With the growing burden of this disease in gastroenterology practices, the identification and treatment of those at risk of developing adverse outcomes (cirrhosis, hepatocellular carcinoma, or liver-related death) has become urgent. In recent years, the development of noninvasive tests (NITs) to identify "at-risk MASH" patients have provided cost-effective algorithms to identify these patients. Although treatment has historically been limited to lifestyle modification, recent FDA approval of resmetirom for noncirrhosis MASH with stages 2 and 3 fibrosis has provided a new  opportunity in the United States to provide these patients with novel treatment options. Other new effective treatment regimens are on the horizon. Given that gastroenterology and hepatology practices in the United States heavily rely on advanced practice providers (APPs) to manage patients with MASLD, the APP Committee of the Global NASH/MASH Council has curated the essentials of day-to-day MASH management for our busy gastrohepatology providers and their APP colleagues. The goal of this document is to equip and mobilize more GI providers with the requisite competencies for the management of at-risk MASH, given the rapidly evolving MASH treatment landscape., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Glenn procedure carries low morbidity and mortality within stages of single-ventricle palliation. However, some patients with Glenn failure need a stage reversal, while others require unanticipated surgical interventions. Our understanding of perioperative factors and outcomes associated with such unexpected interventions is extremely limited., Methods: Patients who underwent unexpected surgery after the Glenn procedure between January 2010 and December 2019 within the Society of Thoracic Surgeons Congenital Heart Surgery Database (STS-CHSD) were identified with a subgroup analysis of those reverting to stage I physiology. Patient's requiring reversal to stage I palliation were matched 1:5 with controls. Multivariable logistic regression analysis was performed to evaluate risk factors for reintervention., Results: A total of 16,913 patients underwent Glenn procedure with 1221 (7.2%) requiring unexpected cardiac surgical intervention and 95 (0.56%) patients required takedown to a stage I. Significant clinical and operative risk factors were identified for such unexpected interventions.The overall mortality after Glenn procedure was 1.2%, while mortality after unexpected reintervention was 6.6% at 30 days and after Glenn takedown was 27.5% at last follow-up. Unexpected surgical intervention and right ventricular dominance were significant risk factors for mortality., Conclusion: Unexpected reinterventions, including need for takedown after the Glenn procedure, are associated with significantly higher mortality. Further studies should focus on improving our patient selection, understanding the risk factors mechanistically, including impact of the right ventricle as systemic ventricle in order to avoid need for unexpected surgical interventions.

Background: The impact of integrase strand-transfer inhibitors (INSTIs) on steatotic liver disease in women with HIV (WWH) is unknown., Methods: Using data collected in the Women's Interagency HIV Study from 2007-2020, change in Fibrosis-4 index (FIB4), aspartate aminotransferase to platelet ratio index (APRI), and non-alcoholic fatty liver disease fibrosis score (NFS) over 5 years was compared between virologically-suppressed WWH who switched to or added an INSTI to their antiretroviral therapy (ART) and WWH remaining on non-INSTI ART. In participants with transient elastography (TE) measures, estimates of hepatic steatosis (controlled attenuation parameter, CAP), fibrosis (liver stiffness, LS), and steatohepatitis (FibroScan-aspartate aminotransferase scores, FAST) were compared by group., Results: A total of 872 WWH (323 INSTI, 549 non-INSTI) were included, and 280 (146 INSTI, 134 non-INSTI) had TE. Of these, 61% were Non-Hispanic Black; mean age was 47 years and body mass index was 31.4 kg/m2. Among non-obese women, those in the INSTI compared to the non-INSTI group had a greater increase in NFS (but not FIB4 or APRI) over time (study group*time, p=0.015). Those in the INSTI compared to non-INSTI group also had greater CAP (+25, 95%CI:0.28-49, p=0.048), LS (+1.23, 1.01-1.49, p=0.038), and FAST scores (+1.97, 1.17-3.31, p=0.011) and a 3.7 (1.2-11.4, p=0.021) greater odds of having hepatic steatosis (CAP≥248 dB/m) within 1 year of starting an INSTI., Conclusions: Hepatic steatosis risk was increased only within the first year following INSTI initiation among WWH. Longitudinal hepatic assessments are warranted to evaluate whether these changes are associated with clinically significant liver disease., (© The Author(s) 2025. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Current clinical guidelines emphasize the significance of rhythm control with catheter ablation but lack guidance on the timing of atrial fibrillation (AF) ablation relative to the diagnosis time. We aim to investigate the latest evidence on the impact of diagnosis to ablation time (DAT) on clinical outcomes after AF ablation., Methods: We searched PubMed, Web of Science, Scopus, Embase, and Cochrane Central Register of Controlled Trials through August 2024. Pairwise, prognostic, and reconstructed time-to-event data meta-analyses were conducted using R V. 4.3.1. Our primary end point was time to first AF recurrence, with secondary end points of all-cause mortality, tamponade, stroke, and heart failure., Results: Our cohort included 23 studies with 43 711 patients. Shorter DAT was significantly associated with reduced AF recurrence across both paroxysmal and persistent AF subgroups ( P <0.01). There was a significant decrease in benefit for paroxysmal AF over time and a slight decrease in benefit for persistent AF over time. However, the benefit remained significant in both over time. DAT per year was significantly associated with a 10% increased risk of AF recurrence. Reconstructed Kaplan-Meier analysis showed that DAT >1 year was significantly associated with a 70% increased risk of AF recurrence in paroxysmal AF and 30% in persistent AF. DAT ≤1 year was significantly associated with decreased all-cause mortality ( P <0.01) and showed a trend toward an association with a lower incidence of stroke ( P =0.08). However, there was no significant difference in heart failure between DAT ≤1 year and DAT >1 year., Conclusions: Early ablation is more beneficial in paroxysmal AF, with a notable decrease in benefit over time, while in persistent AF, the benefit remains significant but slightly decreases over time. Shorter DAT was significantly associated with decreased all-cause mortality and showed a trend toward an association with a lower incidence of stroke., Registration: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42024525542.

Objectives: Opioid use disorder (OUD) is rising among adolescents, highlighting a need for additional treatment approaches in this population. Buprenorphine, a medication for opioid use disorder, is available in multiple formulations. Sublingual buprenorphine is approved for use in patients ages 16 and older. Extended-release buprenorphine is approved only for adults, and studies have not established the safety and efficacy of its use in adolescents younger than age 18. This case series reviews the medical records of adolescents with OUD receiving monthly extended-release buprenorphine subcutaneous injections., Methods: The electronic medical records of six adolescents, younger than 18 years, receiving monthly extended-release buprenorphine in an outpatient setting from February 2022 to April 2024 were reviewed. The primary outcomes of interest were treatment retention, complications, and opioid abstinence during treatment., Results: The patients included in this case series ranged in age from 15 to 17 years at the onset of treatment. The majority of patients, four of the six, were female. At the conclusion of the chart review period in April 2024, all six patients remained on treatment with extended-release buprenorphine. The duration of treatment with extended-release buprenorphine varied among patients from 2 to 13 months. No significant complications were noted. Five patients achieved opioid abstinence for greater than 2 months during treatment., Conclusions: Treatment of OUD in adolescents remains challenging. This case series highlights a need for larger studies to establish the safety and efficacy of extended-release buprenorphine in adolescents younger than 18 years of age., Competing Interests: Conflicts of Interest: None. The authors report no conflicts of interest., (Copyright © 2025 American Society of Addiction Medicine.)

Study Design: retrospective cohort study., Objective: To investigate the relationship between perioperative Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RAs) and postoperative outcomes after spinal fusion in obese and diabetic patient populations., Summary of Background Data: GLP-1 RAs have been shown to be beneficial when used perioperatively in clinical orthopaedic arthroplasty literature. Minimal evidence exists showing efficacy with respect to spinal fusion., Materials and Methods: This retrospective, multi-center study accessed the TriNetX platform, using the research database to identify diabetic patients who underwent spinal fusion between 2008 and 2022. Cohorts were created based on Body-Mass-Index (BMI) and GLP-1 RA usage. Propensity score matching was employed to create balanced cohorts utilizing BMI, Hemoglobin A1c (HbA1c), surgical intervention, as well as other demographic characteristics. Orthopedic outcomes were compared between GLP-1 RA users and non-users. The primary outcomes included post-operative infection, readmission, revision surgery, and quality of life metrics., Results: After matching, the study cohort consisted of 2,263 patients, with 1,560 classified as obese. GLP-1 RA use was associated with significantly reduced post-operative infection rates (obese: HR=0.168 (0.086, 0.328), not obese: HR=0.250 (0.102, 0.612)), fewer revisions (obese: HR=0.505 (0.368, 0.693), not obese: HR=0.439 (0.272, 0.708)), decreased postoperative readmission rates (obese: HR=0.283 (0.243, 0.329), not obese: HR=0.241 (0.193, 0.301)), and reduced mobility abnormalities (obese: HR=0.355 (0.230, 0.549), not obese: HR=0.508 (0.269, 0.959)). No significant differences were observed in rates of fracture rates between GLP-1 RA users and non-users., Conclusions: GLP-1 RA use in spinal fusion patients was associated with improved post-operative outcomes, including lower infection rates, fewer revisions, and better quality of life metrics. These findings suggest that GLP-1 RAs may be a valuable adjunctive therapy in managing surgical outcomes in diabetic and obese patients undergoing spinal fusion. Further prospective and animal-based studies are needed to confirm these findings and explore the underlying mechanisms., Competing Interests: The authors report no conflicts of interest., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Motivation: Understanding cell differentiation and development dynamics is key for single cell transcriptome analysis. Current cell differentiation trajectory inference algorithms face challenges such as high dimensionality, noise, and a need for users to possess certain biological information about the datasets to effectively utilize the algorithms. Here, we introduce Trajectory Inference with Cell-Cell Interaction (TICCI), a novel way to address these challenges by integrating intercellular communication information. In recognizing crucial intercellular communication during development, TICCI proposes Cell-Cell Interactions (CCI) at single cell resolution. We posit that cells exhibiting higher gene expression similarity patterns are more likely to exchange information via biomolecular mediators., Results: TICCI is initiated by constructing a cell-neighborhood matrix using edge weights composed of intercellular similarity and CCI information. Louvain partitioning identifies trajectory branches, attenuating noise, while single-cell entropy (scEntropy) is used to assess differentiation status. The Chu-Liu algorithm constructs a directed least-square model to identify trajectory branches, and an improved diffusion fitted time algorithm computes cell-fitted time in non-connected topologies. TICCI validation on single-cell RNA sequencing (scRNA-seq) datasets confirms the accuracy of cell trajectories, aligning with genealogical branching and gene markers. Verification using extrinsic information labels demonstrates CCI information utility in enhancing accurate trajectory inference. A comparative analysis establishes TICCI proficiency in accurate temporal ordering., Availability and Implementation: Source code and binaries freely available for download at https://github.com/mine41/TICCI, implemented in R (version 4.32) and Python (version 3.7.16) and supported on MS Windows. Authors ensure that the software is available for a full two years following publication., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2025. Published by Oxford University Press.)

Deployments are stressful for both service members and their families. To promote the overall health and welfare of those impacted by military deployment, it is important to identify individual resilience-building resources that service members can employ to strengthen their own well-being, the well-being of their families, and the readiness of the force. This pilot study examines different resilience-building skills that may impact individual well-being, relationship quality, and family satisfaction post-deployment. A cross-sectional sample of 78 married U.S. military enlisted service members (n = 24) and commissioned officers (n = 54) completed the Coping Self-Efficacy Scale, Resilience Scale for Adults, Humor Styles Questionnaire, Mindful Attention Awareness Scale, Dispositional Resilience Scale, the emotional well-being and spirituality subscales of the Work-Life Well-Being Inventory, and the Social Problem-Solving Inventory-Revised. The use of a positive humor style was significantly associated with individual well-being. Spirituality and religious practices were significantly predictive of a service member's family satisfaction. Responding to qualitative open-ended questions, service members identified their top 6 subcategories of stress, which were communication, moving, finances, family separation, children, and future employment during post-deployment. The strengths and resources reported as contributing the most to family effectiveness and well-being were personal character traits, external relationship skills, emotional maturity, and the ability to work. The results identified unique individual resilience-building resources for service members, which contribute to their well-being and the well-being of their families. Findings suggest that training on individual resilience-building resources for service members can offer support to the entire family system following military deployment., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2025. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Left ventricular assist device (LVAD) implantation can be used to manage advanced heart failure. Debates over sex differences in postoperative outcomes of LVAD implantation remain contentious; there is limited evidence available from the continuous-flow era, particularly following the introduction of third-generation devices. This study aimed to conduct a comprehensive, contemporary, and population-based analysis of the sex difference in the in-hospital outcomes following LVAD implantations., Methods: Patients who underwent LVAD implantation were selected from National Inpatient Sample from Q4 2015-2021. Multivariable logistic regression was used to compare in-hospital outcomes between females and males, where demographics, socioeconomic status, primary payer status, hospital characteristics, comorbidities, and transfer/admission status were adjusted., Results: There were 1201 (23.6%) female and 3881 (76.4%) male patients who underwent LVAD implantation. Females and males had comparable in-hospital mortality, MACE, and stroke. However, females had higher diaphragmatic paralysis (aOR = 7.94, 95 CI = 1.46-43.48, p = 0.02). Meanwhile, females had lower cardiogenic shock (aOR = 0.85, 95 CI = 0.73-0.98, p = 0.02), renal complications (aOR = 0.72, 95 CI = 0.62-0.84, p < 0.01), and infection (aOR = 0.70, 95 CI = 0.58-0.86, p < 0.01). Females also had longer hospital length of stay (44.1 ± 40.0 vs. 38.8 ± 30.6 days, p = 0.01) and higher total hospital charges (1293779.0 ± 1182139.0 vs. 1172780.0 ± 917544.0 US dollars, p = 0.04)., Conclusion: In the contemporary era with the introduction of third-generation devices, in-hospital mortality and stroke after LVAD implantation continued to decrease and were comparable in both sexes. However, there are still notable sex-based differences in the complications of LVAD implantation, which underscores the need for sex-specific preoperative risk assessments and tailored perioperative management., (© 2025 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Autosomal recessive deficiency of the IFNAR1 or IFNAR2 chain of the human type I IFN receptor abolishes cellular responses to IFN-α, -β, and -ω, underlies severe viral diseases, and is globally very rare, except for IFNAR1 and IFNAR2 deficiency in Western Polynesia and the Arctic, respectively. We report 11 human IFNAR1 alleles, the products of which impair but do not abolish responses to IFN-α and -ω without affecting responses to IFN-β. Ten of these alleles are rare in all populations studied, but the remaining allele (P335del) is common in Southern China (minor allele frequency ≈2%). Cells heterozygous for these variants display a dominant phenotype in vitro with impaired responses to IFN-α and -ω, but not -β, and viral susceptibility. Negative dominance, rather than haploinsufficiency, accounts for this dominance. Patients heterozygous for these variants are prone to viral diseases, attesting to both the dominance of these variants clinically and the importance of IFN-α and -ω for protective immunity against some viruses., (© 2024 Al Qureshah et al.)

Background & Aims: Up to 15% of ulcerative colitis (UC) patients with an ileo-anal pouch will develop chronic or antibiotic refractory pouchitis. We aimed to evaluate the efficacy and safety of tofacitinib in these refractory patients., Methods: In this prospective single center study, adult UC patients with chronic or antibiotic refractory pouchitis (pouchitis disease activity index [PDAI] ≥ 7) were treated with tofacitinib 10 mg twice daily for 8 weeks. Clinical, biochemical, endoscopic and histologic disease activity was assessed at baseline and at week 8. The primary endpoint was the proportion of patients achieving clinical remission (PDAI < 7 and a reduction of ≥3 points from baseline) or clinical response (decrease ≥2 points from baseline)., Results: Thirteen patients were included and treated with tofacitinib. After 8 weeks, 31% achieved PDAI-defined remission (4/13) and 54% achieved response (7/13). Both the total PDAI score (11 [interquartile range 9-12.75] vs. 8 [4.5-9.75], p = 0.033) and the clinical PDAI subscore (4 [3-4] vs. 2 [0.25-3.75], p = 0.014) decreased significantly from baseline compared to week 8 or early withdrawal, respectively. We did not observe a change in endoscopic or histological PDAI subscores., Conclusion: In this pilot study, clinical remission in patients with chronic pouchitis was achieved in 31% of patients after 8 weeks of treatment with tofacitinib. Total and clinical PDAI dropped significantly compared with baseline, but we did not observe a significant change in endoscopic or histologic disease activity. Presumably, a treatment duration of 8 weeks is insufficient to induce mucosal healing in these refractory patients., (© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

The objective of this study was to evaluate scaphoid, lunate and capitate kinematics after disruption to the primary and secondary scapholunate ligamentous stabilizers, and to assess the effectiveness of scapholunate ligament reconstruction in restoring carpal kinematics post-operatively. Seven upper extremities were harvested, and the scapholunate interosseous ligament (SLIL) was divided. Specimens were mounted onto a computer-controlled dynamic wrist simulator, and simulations of flexion-extension, radial-ulnar deviation, and dart-thrower's motion were undertaken by simulated force application to the wrist tendons. Three-dimensional kinematics of the scaphoid, lunate and capitate were measured using bi-plane X-ray fluoroscopy in the native and ligament deficient state. The SLIL was then reconstructed by either dorsal transarticular loop tenodesis (DTLT), or by the three-ligament tenodesis (3LT) technique, and re-evaluated. SLIL deficiency resulted in significant differences in carpal kinematics compared to that in the healthy wrist across all wrist motions (p < 0.05). The DTLT procedure corrected increased scaphoid ulnar deviation and pronation in the SLIL deficient wrist, but did not significantly improve scaphoid flexion or volar translation of the scaphoid. The 3LT reconstructive technique restored scaphoid flexion and ulnar deviation but did not correct pronation, the increased lunate extension, nor the volar and ulnar translation observed in the ligament deficient wrist. Three-dimensional scaphoid, lunate and capitate motion depends on SLIL integrity, with tears to this ligament resulting in pathological kinematics, which may be partially mitigated with DTLT and 3LT surgical reconstruction. These findings suggest that this surgical reconstruction of the SLIL may not mitigate long-term degenerative joint conditions at the wrist., (© 2025 The Author(s). Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Background: As obligate scavengers, New World vultures (Cathartiformes: Cathartidae) play a key role in carcass removal and disease control. Associated with this ecosystem service, vultures are exposed to the consumption of harmful substances such as poisons, heavy metals, antibiotics, or non-steroidal anti-inflammatory drugs. Monitoring the health status of vulture populations is a priority and an important conservation strategy, and hematologic analysis is a practical and effective method that can be useful for this purpose., Objectives: Report hematologic reference intervals in free-living King vultures (Sarcoramphus papa), one of the least studied New World vulture species., Methods: Red blood cell concentration, packed cell volume, hemoglobin (Hb) concentration, MCV, MCH, MCHC, WBC concentration, differential count and absolute WBC concentration, heterophil to lymphocyte ratio, and total protein concentration were determined. We used a non-parametric method to calculate the reference intervals. In addition, we compared our results with the hematologic measurands reported for the Black vulture (Coragyps atratus), the Andean condor (Vultur gryphus) and the California condor (Gymnogyps californianus)., Results: With the exception of Hb, monocyte, basophil, and eosinophil concentrations, the mean hematologic measurands observed in the King vulture were similar to those recorded for the other New World vulture species, and the heterophil to lymphocyte ratio was lower in the King vulture compared to the Black vulture., Conclusions: In this study, we have reported for the first time the hematologic reference intervals in a free-living population of King vultures in Costa Rica. Future research should consider comparison among free-living New World vulture species., (© 2025 American Society for Veterinary Clinical Pathology.)

Metal hydrides play a significant role in a variety of reactions, including chemical, electrochemical, and photochemical CO 2 reduction. Molecular metal hydrides have the distinct advantage of allowing tunability of their hydricities by rational ligand modifications, with more electron-rich metal hydrides being in general more hydridic. We report here a new approach to generate highly hydridic metal hydrides of the type [Ru(tpy)(LL)(H)] n + by introducing electron-withdrawing substituents into the backbone of the bidentate LL ligand. This strategy enables the generation of the metal hydride [Ru(tpy)(LL)(H)] + at mild negative potentials and further one-electron reduction to the more hydridic [Ru(tpy)(LL)(H)] 0 at a potential window that is redox silent for the more electron-rich metal hydride analogue [Ru(tpy)(bpy)(H)] + . In addition, formate release takes place from the hydride transfer adducts [Ru---HCOO)(tpy)(LL)] 0 rather than from the corresponding formato complexes [Ru(tpy)(LL)(OCHO)] 0 , which would require further reduction to [Ru(tpy)(LL)(OCHO)] - as demonstrated by IR spectroelectrochemistry. The parent [Ru(tpy)(LL)(CH 3 CN)] n + solvento complexes were then tested as catalysts for the reduction of CO 2 to formate in a four-component homogeneous photochemical approach driven by a Ru(II) sensitizer. The results showed selective (>88%) formate production with a record turnover number of ∼50,000 and record turnover frequency of 4.4 s -1 when compared to other molecular catalysts.

Osteogenesis imperfecta (OI) is a multisystem disorder most often caused by pathogenic variants in genes that encode type I collagen. Type I collagen is abundant not only in bone but also in multiple tissues including skin, tendons, cornea, blood vessels, and heart. Thus, OI can be expected to affect cardiovascular system, and there are numerous reports of cardiovascular disease (CVD) in people with OI. However, there is no consensus on how CVD in OI should be assessed or managed. To fill this gap, a multidisciplinary group was convened to develop clinical guidance. The work included a systematic review of the available literature and, using a modified Delphi approach, the development of a series of statements summarizing current knowledge. Fourteen clinical recommendations were developed to guide clinicians, patients, and stakeholders about an approach for CVD in adults with OI. This paper describes how the work was conducted and provides the background and rationale for each recommendation. Furthermore, we highlight knowledge gaps and suggest research priorities for the future study of CVD in OI., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Background: Sex-specific differences in stroke risk factors, clinical presentation, and outcomes are well documented. However, little is known about real-world differences in transient ischemic attack (TIA) hospitalizations and outcomes between men and women., Methods: This was a retrospective cohort study of the 2016 to 2021 Nationwide Readmissions Database in the United States. Adult patients hospitalized for TIA were included. Annual incidences of TIA hospitalizations for men and women were calculated using the US Census Bureau data. Primary end points were 90-day readmission for ischemic stroke or hemorrhage and compared between men and women. Demographics and comorbidities were captured and used to adjust for confounders using propensity score matching and logistic regression models., Results: A total of 588 499 patients were identified; 326 794 (55.5%) were women. The estimated annual incidence of TIA hospitalizations was 42.4 (95% CI, 26.0-58.9) per 100 000 women and 36.2 (95% CI, 23.5-48.9) per 100 000 men (relative risk, 1.17 [95% CI, 1.13-1.21]; P <0.001). Overall, women were older, had higher rates of headache and psychiatric comorbidities, and had lower rates of vascular risk factors compared with men. Women were significantly less likely to be readmitted for ischemic stroke (hazard ratio, 0.86 [95% CI, 0.79-0.93]; P <0.001) and more likely to be readmitted for hemorrhage (hazard ratio, 1.12 [95% CI, 1.04-1.20]; P <0.001), with similar rates of antithrombotic use at the time of readmissions ( P >0.05). Compared with ischemic stroke, hemorrhage readmissions were significantly associated with lower odds of home discharge (odds ratio, 0.83 [95% CI, 0.76-0.91]; P <0.001) and higher odds of death (odds ratio, 3.01 [95% CI, 2.35-3.87]; P <0.001)., Conclusions: Women have a higher incidence of TIA hospitalizations than men, which may be due to higher rates of nonischemic causes of transient neurological symptoms as evidenced by differences in baseline characteristics and lower rates of subsequent ischemic stroke. Future studies are needed to better characterize transient neurological symptoms in women to avoid excess hospitalizations and unnecessary treatments that may increase hemorrhage risk., Competing Interests: Dr Payabvash reports compensation from AI Medical AG for other services and compensation from Sam Payabvash LLC for consultant services. Dr Chaturvedi reports grants from Boehringer Ingelheim, Mayo Clinic, and employment by the University of Maryland. Dr Gandhi reports grants from the NIH Clinical Center, MicroVention, Inc, the University of Calgary, Focused Ultrasound Foundation, and InSightec, Ltd. The other authors report no conflicts.

Background: In 2020, countries implemented universal surveillance to detect and monitor SARS-CoV-2 cases. Although crucial for early monitoring efforts, universal surveillance is resource intensive. To understand the implications of transitioning from universal to sentinel surveillance for monitoring SARS-CoV-2 transmissibility, morbidity and mortality, and disease seriousness, we compared measures of SARS-CoV-2 reported from both surveillance strategies in Argentina, Chile, and Mexico., Methods: We obtained weekly case counts in Argentina, Chile, and Mexico, in periods when both universal and sentinel surveillance were ongoing. To assess the countries' surveillance strategies, we measured the proportion of total sites that were included in sentinel surveillance. We compared eight measures of SARS-CoV-2 transmissibility, morbidity and mortality, and disease seriousness between sentinel and universal surveillance and assessed the correlation between the two strategies for the eight measures. Pearson's and Spearman's correlation was classified as very strong (r(s)=0.8-1.0), strong (r(s)=0.60-0.79), moderate (r(s)=0.50-0.59), or poor (r<0.50)., Results: The proportion of total sites included in sentinel surveillance was 5.8% for Argentina, 1.1% for Chile, and 7.6% for Mexico. A total of 21 measures were calculated (8 for Mexico, 8 for Chile, and 5 for Argentina). Of these, 17 showed consistency between the two surveillance strategies, with strong or very strong correlations (r=0.66-0.99): all 8 measures for Mexico, 6 of 8 measures for Chile, and 3 out of 5 measures for Argentina.. Each country had at least one measure reflecting transmissibility and at least one reflecting morbidity and mortality for which the correlation was strong or very strong. Chile and Mexico also had at least one measure of disease seriousness for which the correlation was strong., Conclusions: Our findings suggest that the integration of SARS-CoV-2 into national sentinel surveillance can yield information comparable to that provided by nationwide universal surveillance for measures related to SARS-CoV-2 transmissibility, morbidity and mortality, and seriousness of disease., (© The Author(s) 2025. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: We estimate annual viral influenza-associated mild-to-moderate illness, hospitalizations, and deaths in six South American countries (Argentina, Brazil, Chile, Ecuador, Paraguay, and Uruguay) during the 2015-2019 influenza seasons as a first step in evaluating the full value of influenza vaccination in the subregion., Methods: We applied a multiplier methodology using monthly hospital discharge and vital statistics death records, influenza surveillance data, and population projections to estimate mild-to-moderate influenza-associated illness, hospitalizations, and deaths. We estimated the uncertainty bounds based on the 2.5th and 97.5th of the Monte Carlo simulated distributions for the number of cases and obtained the ranges from the minimum value of the 2.5th percentile and the maximum value of the 97.5th percentile., Results: In selected countries with a total population of 307 million people, the yearly influenza-associated burden of disease ranged between 51 and 78 million mild-to-moderate influenza illnesses, between 323,379 and 490,049 hospitalizations, and between 22,662 and 46,971 deaths during the 2015-2019 influenza seasons., Conclusions: Each year, influenza is associated with millions of illnesses, hundreds of thousands of hospitalizations and tens of thousands of deaths in six South American countries, affecting a significant portion of the population. Such findings can be used to estimate the number of illnesses averted through vaccination programs and the cost-benefit of influenza vaccines., (© The Author(s) 2025. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Given the substantial expansion of the US cannabis market and the impact of cannabis advertising exposure on use, cannabis marketing surveillance is needed to inform regulations and protect consumers., Methods: Using 2020-2021 Vivvix advertising data from 4 US cannabis companies (Cresco, Mindy's, MedMen, and Uncle Ike's), we examined (1) general advertising characteristics (eg, number of unique ads and ad occurrences, ad expenditures, market, and media channel); and (2) ad content (ie, headlines and imagery) and placement (ie, source themes, eg, specific websites and magazines), overall and by company., Results: There were 399 unique ads and 1171 occurrences, totaling $488,617 in expenditures. Cresco and Uncle Ike's accounted for most unique ads (~45% each); Cresco represented the majority of ad occurrences (52.4%) and expenditures (63.4%). Most ads were disseminated via online displays (occurrences = 69.2%; expenditures = 45.8%). The primary source for ad dissemination was news/weather (occurrences = 36.3%; expenditures = 40.2%). Ad headlines most frequently emphasized product type (occurrences = 40.1%; expenditures = 37.0%). Visual strategies to attract attention included gifs (occurrences = 63.6%; expenditures = 71.1%). Companies differed in their marketing strategies (ie, volume, markets, channels, and content)., Conclusions: Findings underscore the need to restrict cannabis marketing, for example, restricting ad content and marketing channels. This may reduce exposure to cannabis marketing, which is associated with cannabis perceptions and use., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: There is a growing interest among medical students to learn about global surgery and how they can incorporate it into their further training in residency. This study addresses US-based medical student perceptions of global surgery, medical school experiences, and career plans., Methods: A cross-sectional survey study of US-based medical students was performed. Univariate and multivariable regression models were constructed to assess the impact of student experiences during medical school and mentor experiences on global surgery perceptions and career plans. Career plans for international surgical mission trips and for global surgery advocacy/research were further evaluated., Results: Of the 708 responses, 251 (34.6%) students indicated interest in global surgery. Global surgery curricular experiences during medical school were associated with increased odds of believing that global surgery topics should be included in medical school curricula (OR = 2.42, p = 0.021) and having career plans for global surgery research or advocacy (OR = 3.72, p = 0.002). Students with mentors with global surgery research experience were more likely to have career plans for global surgery research or advocacy (OR = 4.36, p = 0.019). Student participation in global health research was associated with lower odds of having career plans for international surgical mission trips (OR = 0.22, p < 0.001)., Conclusion: Students with more experience in global surgery view it more favorably, and have greater odds of participating in global surgery in their future careers. There is a desire among the respondent medical students for more global surgery education and mentoring among medical institutions. Therefore, medical schools may benefit by offering more global surgery opportunities at their institutions., (Copyright © 2025 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Applying both culture-independent and -dependent approaches, bacterial diversity of marine biofilm communities colonising polyvinyl chloride panels submerged in Terra Nova Bay (Ross Sea, Antarctica) was investigated. Panels were deployed in two sites subjected to a different degree of anthropogenic impact (Road Bay [RB] impacted site and Punta Stocchino [PTS] control site). Biofilm samples were collected after 3 or 12 months to evaluate both short- and long-term microbial colonisation. Taxonomic composition of the microbial community was studied by 16S rRNA gene amplicon sequencing. Proteobacteria was the predominant phylum, followed by Bacteroidetes, Actinobacteria, Verrucomicrobia and Firmicutes. Impacted RB biofilms were found to contain a relevant fraction of potentially pathogenic bacterial genera, accounting for 27.49% of the whole community. A total of 86 psychrotolerant bacterial strains were isolated from the biofilm samples using culture-dependent techniques designed to enrich in Actinobacteria. These strains were assigned to three different phyla: Actinobacteria (54.65%), Firmicutes (32.56%) and Proteobacteria (12.79%). 2.73% of genera identified by metabarcoding were recovered also through cultivation, while 11 additional genera were uniquely yielded by cultivation. Functional screening of the isolates revealed their hydrolytic and oxidative enzyme activity patterns, giving new insights into the metabolic and biotechnological potential of microbial biofilm communities in Terra Nova Bay seawater., (© 2025 The Author(s). Environmental Microbiology published by John Wiley & Sons Ltd.)

Artificial neural networks have advanced due to scaling dimensions, but conventional computing struggles with inefficiencies due to memory bottlenecks. In-memory computing architectures using memristor devices offer promise but face challenges due to hardware non-idealities. This work proposes layer ensemble averaging-a hardware-oriented fault tolerance scheme for improving inference performance of non-ideal memristive neural networks programmed with pre-trained solutions. Simulations on an image classification task and hardware experiments on a continual learning problem with a custom 20,000-device prototyping platform show significant performance gains, outperforming prior methods at similar redundancy levels and overheads. For the image classification task with 20% stuck-at faults, accuracy improves from 40% to 89.6% (within 5% of baseline), and for the continual learning problem, accuracy improves from 55% to 71% (within 1% of baseline). The proposed scheme is broadly applicable to accelerators based on a variety of different non-volatile device technologies., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)