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Geum Joon Cho,1 Michael S Oh,2 Min-Jeong Oh,1 Keon Vin Park,3 Sung Won Han,3 Young Kwang Chae2,4 1Department of Obstetrics and Gynecology, Korea University College of Medicine, Seoul, Republic of Korea; 2Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; 3School of Industrial Management Engineering, Korea University, Seoul, Republic of Korea; 4Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL 60611, USACorrespondence: Young Kwang ChaeDepartment of Medicine, Northwestern University Feinberg School of Medicine, 645 N. Michigan Avenue, Suite 1006, Chicago, IL 60611, USATel +1 312-926-4248Email ychae@nm.orgBackground: The effect of blood transfusions on the risk of developing primary cancer remains unclear, especially when administered in the peripartum period.Materials and Methods: We conducted a retrospective cohort study of 270,529 pregnant women who delivered between January 1, 2007 and December 31, 2009, with data obtained from three national databases in South Korea. From this cohort, we identified 4569 patients who received peripartum blood transfusions. We calculated hazard ratios (HRs) for new diagnoses of cancer and adjusted them for relevant clinical factors using a Cox proportional hazards model.Results: During follow-up, patients who received peripartum transfusions had an increased risk of developing cancer, with an adjusted HR of 1.16 (95% confidence interval [CI], 1.01– 1.34). In a subgroup analysis, this risk was significant only among patients who received 3 or more units of blood, with an adjusted HR of 1.40 (95% CI, 1.10– 1.79). Increased risk after transfusions were seen with brain, lung, ovarian, and gallbladder cancers. The difference in cancer risk between the transfusion and no-transfusion groups remained significant during both the first (1.29% vs 1.07%, p < 0.01) and second year (0.74% vs 0.56%, p < 0.01) after delivery.Conclusion: Receipt of 3 or more blood transfusions in the peripartum period was associated with a significantly increased risk of developing cancer. Prospective studies should be pursued to further understand the link between blood transfusions and long-term oncologic risks.Keywords: blood transfusion, pregnancy, cancer, immunomodulation

Human adipose-derived mesenchymal stem cells (hAMSCs) are capable of immunomodulation and regeneration after neural injury. For these reasons, hAMSCs have been investigated as a promising stem cell candidate for stroke treatment. However, noninvasive experiments studying the effects of grafted stem cells in the host brain have not yet been reported. Cerebrospinal fluid (CSF), which can be collected without sacrificing the subject, is involved in physiological control of the brain and reflects the pathophysiology of various neurological disorders of the central nervous system (CNS). Following stem cell transplantation in a stroke model, quantitative analysis of CSF proteome changes can potentially reveal the therapeutic effect of stem cells on the host CNS. We examined hAMSC-secreted proteins obtained from serum-free culture medium by liquid chromatography-tandem mass spectrometry (LC-MS/MS), which identified several extracellular matrix proteins, supporting the well-known active paracrine function of hAMSCs. Subsequently, we performed label-free quantitative proteomic analysis on CSF samples from rat stroke models intravenously injected with hAMSC (experimental) or phosphate buffered saline (control). In total, 524 proteins were identified; among them, 125 and 91 proteins were increased and decreased with hAMSC treatment, respectively. Furthermore, gene set enrichment analysis revealed three proteins, 14-3-3 theta, MAG, and neurocan, that showed significant increases in the hAMSC-treated model; these proteins are core members of neurotrophin signaling, nerve growth factor (NGF) signaling, and glycosaminoglycan metabolism, respectively. Subsequent histological and neurologic function experiments validated proliferative neurogenesis in the hAMSC-treated stroke model. We conclude that (i) intravenous injection of hAMSCs can induce neurologic recovery in a rat stroke model and (ii) CSF may reflect the therapeutic effect of hAMSCs. Additionally, proteins as 14-3-3 theta, MAG, and neurocan could be considered as potential CSF biomarkers of neuroregeneration. These CSF proteome profiling results would be utilized as valuable resource in further stroke studies.

Parkinson's disease (PD), one of the most common neurodegenerative disorders, is characterised by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) to the striatum (ST), and involves oxidative stress. Mulberry fruit from Morus alba L. (Moraceae) is commonly eaten, and has long been used in traditional oriental medicine. It contains well-known antioxidant agents such as anthocyanins. The present study examined the protective effects of 70% ethanol extract of mulberry fruit (ME) against neurotoxicity in in vitro and in vivo PD models. In SH-SY5Y cells stressed with 6-hydroxydopamine (6-OHDA), ME significantly protected the cells from neurotoxicity in a dose-dependent manner. Other assays demonstrated that the protective effect of ME was mediated by its antioxidant and anti-apoptotic effects, regulating reactive oxygen species and NO generation, Bcl-2 and Bax proteins, mitochondrial membrane depolarisation and caspase-3 activation. In mesencephalic primary cells stressed with 6-OHDA or 1-methyl-4-phenylpyridinium (MPP+), pre-treatment with ME also protected dopamine neurons, showing a wide range of effective concentrations in MPP+-induced toxicity. In the sub-acute mouse PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), ME showed a preventative effect against PD-like symptoms (bradykinesia) in the behavioural test and prevented MPTP-induced dopaminergic neuronal damage in an immunocytochemical analysis of the SNpc and ST. These results indicate that ME has neuroprotective effects in in vitro and in vivo PD models, and that it may be useful in preventing or treating PD. [ABSTRACT FROM AUTHOR]

BACKGROUND: One of the most effective methods for teaching physical diagnosis may be standardized patient instructors. PURPOSE: To determine if a lecture plus standardized patient instructors with small-group sessions is more effective than a lecture alone for teaching the evaluation of patients with abdominal pain. METHODS: Control (class of 2001) and intervention (class of 2002) groups both attended a lecture on the abdominal examination. The intervention group then underwent an exercise with standardized patient instructors and a review session with surgical faculty. An evaluation 18 months later used standardized patient instructors to complete evaluations assessing history-taking and physical examination skills. RESULTS: The intervention group performed significantly better than the control group on both the history and the physical examination subscales. CONCLUSION: It is possible to have an important, measurable, and lasting effect on physical examination skills by adding standardized patient instructors and small-group discussion to a lecture presentation. [ABSTRACT FROM AUTHOR]

This study involved 1202 patients who were placed into low adherence or high adherence groups based on their answers to questionnaires. The attitudes of each group were compared for a variety of adherence behaviors. Patients who reported high levels of adherence tended to have attitudes more in accord with diabetes experts. Members of the high adherence group strongly supported the need for special training for health care professionals who treat diabetes, favored team care, accepted the importance of patient compliance, acknowledged the seriousness of non-insulin-dependent diabetes mellitus (NIDDM), and recognized the relationship between glucose control and complications. Differences in attitudes between high- and low adherence groups were more prevalent for difficult adherence areas, eg, diet and exercise, than for easy adherence areas, eg, carrying sweets or diabetic identification. An understanding of patients' attitudes can help diabetes educators and patients develop realistic and relevant self-care plans. [ABSTRACT FROM AUTHOR]

To determine the efficacy of and need for patient education methods and media, a needs assessment was sent to 816 members of the American Association of Diabetes Educators. Respondents (n = 325, 40%) included 62% RNs, 36% RDs, 1% other; 62% CDEs. Their mean number of years experience in diabetes education was 8.5, and 99% routinely provided patient education. Respondents indicated that videotapes and slide tapes were the most educationally effective media and books and audiotapes were the least effective. Booklets and videotapes were the most cost-effective and computer-assisted instruction the least effective. While respondents perceived one-to-one counseling, skills training, and diabetes content sessions to be the three most educationally effective methods, support groups and large and small discussion groups were seen as the three most cost-effective educational methods. Among nine potential barriers to quality patient education listed, educators rated lack of third-party reimbursement as a major barrier most frequently and national availability of quality education materials as a barrier least frequently. [ABSTRACT FROM AUTHOR]

The treatment of non-small cell lung cancer has made major strides with the use of immune checkpoint inhibitors, but there remains a significant need for therapies that can overcome immunotherapy resistance. Dendritic cell (DC) vaccines have been proposed as a therapy that can potentially enhance the antitumor immune response. We have embarked on a phase I clinical trial of a vaccine consisting of monocyte-derived DCs (moDCs) modified to express the chemokine CCL21 (CCL21-DC) given in combination with pembrolizumab. Here, we report a comprehensive characterization of this CCL21-DC vaccine and interrogate the effects of multiple factors in the manufacturing process. We show that the cellular makeup of the CCL21-DC vaccine is heterogeneous due to the presence of passenger lymphocytes at a proportion that is highly variable among patients. Single cell RNA sequencing of vaccines revealed further heterogeneity within the moDC compartment, with cells spanning a spectrum of DC phenotypes. Transduction with a CCL21-containing adenoviral vector augmented CCL21 secretion by moDCs but otherwise had a minimal effect on vaccine characteristics. A single freeze-thaw cycle for stored vaccines was associated with minor alterations to the DC phenotype, as was the use of healthy donors rather than patient autologous blood. Our results highlight important considerations for the production of DC vaccines and identify underexplored factors that may affect their efficacy and immunologic impact.

Alzheimer's disease (AD) is a representative neurodegenerative disease that is characterized by the overaccumulation of amyloid beta (Aβ) proteins. Since AD is accompanied by excessive oxidative stress, which aggravates neurological pathologies, the use of antioxidants has been considered to prevent disease development. NXP031, a combination of vitamin C (VitC) and an optimized aptamer that binds to VitC and stabilizes the reactivity of VitC, was designed. This study aimed to evaluate the effects of NXP031 on AD pathology, including Aβ accumulation, Aβ-induced oxidative stress, neuronal damage, and neuroinflammation. When NXP031 was administered to 5xFAD transgenic mice, NXP031 exerted a strong inhibitory action on Aβ accumulation, superior to that of VitC, by inducing an increase in Aβ-degrading endopeptidase expression. NXP031 diminished lipid peroxidation levels, activated Nrf2-mediated antioxidant pathways, and suppressed overactivated neuroinflammation. An in vitro study using Neuro2a cells revealed that NXP031 protects the cells against oxidative stress by regulating the MAPK signaling pathway-mediated apoptosis. Additionally, the neuroprotective effects of NXP031 were confirmed in a dose-dependent manner when administered to intrahippocampal Aβ-injected mice, as NXP031 attenuated memory decline, neuronal apoptosis, synaptic degeneration, and excessive glial activation, and reduced NOX-2 expression in the hippocampus. Taken together, NXP031 reduced the Aβ burden by regulating Aβ-degeneration and attenuated memory impairment, neuronal death, synaptic degeneration, and neuroinflammation induced by Aβ toxicity. These results suggest the potential of NXP031 as a therapeutic agent for AD., 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. Published by Elsevier Inc.)

Alzheimer's disease (AD) presents a growing societal challenge, driven by an aging population. It is characterized by neurodegeneration linked to β-amyloid (Aβ) and tau protein aggregation. Reactive glial cell-mediated neuroinflammation exacerbates disease progression by facilitating the accumulation of Aβ and impairing its clearance, thus highlighting potential therapeutic targets. Aerial parts of Artemisia iwayomogi (AIH), a kind of mugwort, has been consumed as a medicinal herb in East Asia for relieving inflammation-related diseases. Previously, AIH was found to exert potent inhibitory effects on neuroinflammation. This study aimed to examine whether AIH mitigates AD pathogenesis by regulating neuroinflammation and reducing Aβ deposition. AIH treatment to primary mixed glial cultures attenuated the pro-inflammatory responses evoked by Aβ stimulation. When treated to 5 × familial AD (5xFAD) mice, AIH improved learning and cognitive ability and reduced Aβ burden in the brain. AIH suppressed glial overactivation, as well as inhibited the expressions of pro-inflammatory mediators in the brain. Moreover, AIH regulated AKT signaling and elevated the expression of autophagy-lysosomal mediators in vitro. It was confirmed that lysosome-associated membrane protein 1 (LAMP1) was increased in the Aβ-associated microglia in the mouse hippocampus. Finally, it was observed that tau phosphorylation was alleviated, and synaptic protein expression was increased in AIH-treated 5xFAD mice. Overall, this study demonstrated that AIH ameliorated excessive neuroinflammation and Aβ accumulation by regulating microglial activation and autophagy-lysosomal pathway, thereby suggesting AIH as a promising therapeutic candidate for AD treatment., (© 2024. The Author(s), under exclusive licence to American Aging Association.)

Electron-transporting transparent conducting oxides (TCOs) are a commercial reality, however, hole-transporting counterparts are far more challenging because of limited material design. Here, we propose a strategy for enhancing the hole conductivity without deteriorating the band gap ( E g ) and workfunction ( Φ ) by Cu incorporation in a strongly correlated NiWO 4 insulator. The optimal Cu-doped NiWO 4 (Cu 0.185 Ni 0.815 WO 4 ) exhibits a resistivity reduction of ∼10 9 times versus NiWO 4 as well as band-like charge transport with the hole mobility approaching 7 cm 2 V -1 s -1 at 200 K, a deep Φ of 5.77 eV, and E g of 2.8 eV. Experimental and theoretical data reveal that the strength of the electron correlation in NiWO 4 is unaffected by Cu incorporation, while the promoted polarizability weakens electron-phonon coupling, promoting the formation of large polarons. Quantum dot light-emitting and oxide p/n junction devices incorporating Cu 0.185 Ni 0.815 WO 4 exhibit remarkable performances, demonstrating that our approach can be deployed to discover new p-type TCOs.

This study aimed to investigate the association between non-traditional lipid profiles and the risk of 1-year vascular events in patients who were already using statins before stroke and had admission LDL-C < 100 mg/dL. This study was an analysis of a prospective, multicenter, nationwide registry of consecutive patients with acute ischemic stroke patients who treated with statin before index stroke and LDL-C < 100 mg/dL on admission. Non-traditional lipid profiles including non-HDL, TC/HDL ratio, LDL/HDL ratio, and TG/HDL ratio were analyzed as a continuous or categorical variable. The primary vascular outcome within one year was a composite of recurrent stroke (either hemorrhagic or ischemic), myocardial infarction (MI) and all-cause mortality. Hazard ratios (95% Cis) for 1-year vascular outcomes were analyzed using the Cox PH model for each non-traditional lipid profiles groups. A total of 7028 patients (age 70.3 ± 10.8years, male 59.8%) were finally analyzed for the study. In unadjusted analysis, no significant associations were observed in the quartiles of LDL/HDL ratio and 1-year primary outcome. However, after adjustment of relevant variables, compared with Q1 of the LDL/HDL ratio, Q4 was significantly associated with increasing the risk of 1-year primary outcome (HR 1.48 [1.19-1.83]). For the LDL/HDL ratio, a linear relationship was observed (P for linearity < 0.001). Higher quartiles of the LDL/HDL ratio were significantly and linearly associated with increasing the risk of 1-year primary vascular outcomes. These findings suggest that even during statin therapy with LDL-C < 100 mg/dl on admission, there should be consideration for residual risk based on the LDL/HDL ratio, following stroke., (© 2024. The Author(s).)

Depression is a debilitating mood disorder that causes persistent feelings of sadness, emptiness, and a loss of joy. However, the clinical efficacy of representative drugs for depression, such as selective serotonin reuptake inhibitors, remains controversial. Therefore, there is an urgent need for more effective therapies to treat depression. Neuroinflammation and the hypothalamic-pituitary-adrenal (HPA) axis are pivotal factors in depression. Inulae Flos (IF), the flower of Inula japonica Thunb, is known for its antioxidant and anti-inflammatory effects. This study explored whether IF alleviates depression in both in vitro and in vivo models. For in vitro studies, we treated BV2 and PC12 cells damaged by lipopolysaccharides or corticosterone (CORT) with IF to investigate the mechanisms of depression. For in vivo studies, C57BL/6 mice were exposed to chronic restraint stress and were administered IF at doses of 0, 100, and 300 mg/kg for 2 weeks. IF inhibited pro-inflammatory mediators, such as nitric oxide, inducible nitric oxide synthase, and interleukins in BV2 cells. Moreover, IF increased the viability of CORT-damaged PC12 cells by modulating protein kinase B, a mammalian target of the rapamycin pathway. Behavioral assessments demonstrated that IF reduced depression-like behaviors in mice. We found that IF reduced the activation of microglia and astrocytes, and regulated synapse plasticity in the mice brains. Furthermore, IF lowered elevated CORT levels in the plasma and restored glucocorticoid receptor expression in the hypothalamus. Collectively, these findings suggest that IF can alleviate depression by mitigating neuroinflammation and recovering dysfunction of the HPA-axis., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Sex differences in stroke outcomes are notable, with women experiencing higher incidence rates, greater disability-adjusted life years, and poorer recovery compared to men, even after adjusting for age and comorbidities. Despite the disproportionate burden in women, studies have reported that women are less likely to receive appropriate stroke treatment than men., Aim: This study investigated temporal trends of sex differences in acute reperfusion therapy and early outcomes in patients with acute ischemic stroke over 10 years in South Korea., Methods: A retrospective analysis of Korean Stroke Registry included patients with acute ischemic stroke from 2012 to 2021. The study outcomes were the temporal trends of acute reperfusion therapy and early outcomes over 10 years in men and women, respectively. In addition, this study analyzed the temporal trends of sex differences in these parameters during the same period. Early outcomes include the proportions of favorable functional outcomes at discharge, discharge patterns, and in-hospital mortality., Results: A total of 93,692 patients (68.4 years, 40.1% women) with acute ischemic stroke were finally enrolled. Women had a higher age at stroke onset, a higher prevalence of atrial fibrillation, and more severe strokes than men. Women had lower proportion of favorable functional outcomes at discharge and higher proportion of in-hospital mortality compared to men each year. The proportion of patients who received intravenous thrombolysis was lower or similar in women compared to men in most years, and the proportion of patients who received endovascular thrombectomy did not significantly differ between sexes annually. Sex differences in acute reperfusion therapy remained unchanged over 10 years., Conclusion: Women have received acute reperfusion therapy at similar or lower rates than men and experienced poorer outcomes, despite having more stroke risk factors and often more severe strokes., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: W.K.S. received honoraria for lectures from Otsuka Korea, Dong-A Pharmaceutical Co., Ltd., study grants from Dong-A ST.

It is uncertain whether the prognostic power of white matter hyperintensity (WMH) on post-stroke outcomes is modulated as a function of initial neurological severity, a critical determinant of outcome after stroke. This multi-center MRI study tested if higher WMH quintiles were associated with 3-month poor functional outcome (modified Rankin Scale ≥ 3) for mild versus moderate-to-severe ischemic stroke. Mild and moderate-to-severe stroke were defined as admission National Institute of Health Stroke Scale scores of 1-4 and ≥ 5, respectively. Mean age of the enrolled patients (n = 8918) was 67.2 ± 12.6 years and 60.1% male. The association between WMH quintiles and poor functional outcome was modified by stroke severity (p-for-interaction = 0.008). In mild stroke (n = 4994), WMH quintiles associated with the 3-month outcome in a dose-dependent manner for the 2nd to 5th quintile versus the 1st quintile, with adjusted-odds-ratios (aOR [95% confidence interval]) being 1.29 [0.96-1.73], 1.37 [1.02-1.82], 1.60 [1.19-2.13], and 1.89 [1.41-2.53], respectively. In moderate-to-severe stroke (n = 3924), however, there seemed to be a threshold effect: only the highest versus the lowest WMH quintile was significantly associated with poor functional outcome (aOR 1.69 [1.29-2.21]). WMH burden aggravates 3-month functional outcome after mild stroke, but has a lesser modulatory effect for moderate-to-severe stroke, likely due to saturation effects., (© 2024. The Author(s).)

Background: We assessed the influence of prior non-vitamin K antagonist (NOAC) use on stroke outcomes after endovascular treatment (EVT) in patients at a high risk of stroke based on their pre-stroke CHA2DS2-VASc score, and compared them with those who did not use any antithrombotic (NAU) or antiplatelet (APT) agents., Methods: Data were collected from a multicenter database comprising consecutive acute ischemic stroke patients who underwent EVT during a span of 103 months. We evaluated pre-stroke CHA2DS2-VASc scores in enrolled patients and measured instances of successful reperfusion and symptomatic hemorrhagic transformation (SHT) following EVT as the main outcome measures., Results: Among 12 807 patients with acute ischemic stroke, 3765 (29.4%) had a history of atrial fibrillation. Of these, 418 patients with CHA2DS2-VASc scores ≥2 received EVT alone. The prior NOAC group showed higher successful reperfusion rates compared with the prior NAU and APT groups (p=0.04). Multivariate analysis revealed that prior NOAC use increased the likelihood of successful reperfusion after EVT (OR [95% CI] 2.54 [1.34 to 4.83], p=0.004) and improved stroke outcomes, while the prior APT group did not. Furthermore, the prior NOAC use group was not associated with SHT after EVT. Propensity score matching confirmed these findings., Conclusion: Prior use of NOAC is associated with improved outcomes in high-risk stroke patients (pre-stroke CHA2DS2-VASc score ≥2) undergoing EVT., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Predicting long-term mortality is essential for understanding prognosis and guiding treatment decisions in patients with ischemic stroke. Therefore, this study aimed to develop and validate the method for predicting 1- and 5-year mortality after ischemic stroke., Methods: We used data from the linked dataset comprising the administrative claims database of the Health Insurance Review and Assessment Service and the Clinical Research Center for Stroke registry data for patients with acute stroke within 7 days of onset. The outcome was all-cause mortality following ischemic stroke. Clinical variables linked to long-term mortality following ischemic stroke were determined. A nomogram was constructed based on the Cox's regression analysis. The performance of the risk prediction model was evaluated using the Harrell's C-index., Results: This study included 42,207 ischemic stroke patients, with a mean age of 66.6 years and 59.2% being male. The patients were randomly divided into training (n = 29,916) and validation (n = 12,291) groups. Variables correlated with long-term mortality in patients with ischemic stroke, including age, sex, body mass index, stroke severity, stroke mechanisms, onset-to-door time, pre-stroke dependency, history of stroke, diabetes mellitus, hypertension, coronary artery disease, chronic kidney disease, cancer, smoking, fasting glucose level, previous statin therapy, thrombolytic therapy, such as intravenous thrombolysis and endovascular recanalization therapy, medications, and discharge modified Rankin Scale were identified as predictors. We developed a predictive system named Stroke Measures Analysis of pRognostic Testing-Mortality (SMART-M) by constructing a nomogram using the identified features. The C-statistics of the nomogram in the developing and validation groups were 0.806 (95% confidence interval (CI), 0.802-0.812) and 0.803 (95% CI, 0.795-0.811), respectively., Conclusion: The SMART-M method demonstrated good performance in predicting long-term mortality in ischemic stroke patients. This method may help physicians and family members understand the long-term outcomes and guide the appropriate decision-making process., 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.

This report presents the latest statistics on the stroke population in South Korea, sourced from the Clinical Research Collaborations for Stroke in Korea-National Institute for Health (CRCS-K-NIH), a comprehensive, nationwide, multicenter stroke registry. The Korean cohort, unlike western populations, shows a male-to-female ratio of 1.5, attributed to lower risk factors in Korean women. The average ages for men and women are 67 and 73 years, respectively. Hypertension is the most common risk factor (67%), consistent with global trends, but there is a higher prevalence of diabetes (35%) and smoking (21%). The prevalence of atrial fibrillation (19%) is lower than in western populations, suggesting effective prevention strategies in the general population. A high incidence of large artery atherosclerosis (38%) is observed, likely due to prevalent intracranial arterial disease in East Asians and advanced imaging techniques. There has been a decrease in intravenous thrombolysis rates, from 12% in 2017-2019 to 10% in 2021, with no improvements in door-to-needle and door-to-puncture times, worsened by the coronavirus disease 2019 pandemic. While the use of aspirin plus clopidogrel for non-cardioembolic stroke and direct oral anticoagulants for atrial fibrillation is well-established, the application of direct oral anticoagulants for non-atrial fibrillation cardioembolic strokes in the acute phase requires further research. The incidence of early neurological deterioration (13%) and the cumulative incidence of recurrent stroke at 3 months (3%) align with global figures. Favorable outcomes at 3 months (63%) are comparable internationally, yet the lack of improvement in dependency at 3 months highlights the need for advancements in acute stroke care., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Fluxapyroxad, a persistent fungicide in soil, was investigated for differences in residue dissipation in Chinese cabbage and spring scallion through the application methods of soil, foliar, and systemic treatment. Soil application of 0.4% granule fluxapyroxad resulted in residues up to 0.09 mg kg -1 in the scallion, while it did not contribute to the residues in the harvested cabbage. The 50% dissipation time (DT50) of fluxapyroxad in the scallion was 6.8 days. The residues from systemic treatment were highly correlated with foliar application in both the cabbage and the scallion, and the initial residue and DT50 values were similar for foliar and systemic treatments. In comparing the residues from the systemic treatments between the two crops, the initial residue was 3.11 and 0.22 mg kg -1 in the cabbage and the scallion after the systemic treatment, respectively. The DT50 values were 2.6 and 12.2 days in the cabbage and the scallion, respectively. The theoretical dilution effect due to crop growth was higher for the cabbage (4-fold) than for the scallion (1.2-fold), and the half-lives of fluxapyroxad without considering the dilution effect were 6.4 days in the cabbage and 17.8 days in the scallion. Thus, the residue difference was drastically reduced after 14 days from the last treatment.

Parkinson's disease (PD) is a neurodegenerative disease caused by the death of dopaminergic neurons in the nigrostriatal pathway, leading to motor and non-motor dysfunctions, such as depression, olfactory dysfunction, and memory impairment. Although levodopa (L-dopa) has been the gold standard PD treatment for decades, it only relieves motor symptoms and has no effect on non-motor symptoms or disease progression. Prior studies have reported that 6-shogaol, the active ingredient in ginger, exerts a protective effect on dopaminergic neurons by suppressing neuroinflammation in PD mice. This study investigated whether cotreatment with 6-shogaol and L-dopa could attenuate both motor and non-motor symptoms and dopaminergic neuronal damage. Both 6-shogaol (20 mg/kg) and L-dopa (80 mg/kg) were orally administered to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid- induced PD model mice for 26 days. The experimental results showed that L-dopa alleviated motor symptoms, but had no significant effect on non-motor symptoms, loss of dopaminergic neuron, or neuroinflammation. However, when mice were treated with 6-shogaol alone or in combination L-dopa, an amelioration in both motor and non-motor symptoms such as depression-like behavior, olfactory dysfunction and memory impairment was observed. Moreover, 6-shogaol-only or co-treatment with 6-shogaol and L-dopa protected dopaminergic neurons in the striatum and reduced neuroinflammation in the striatum and substantia nigra. Overall, these results suggest that 6-shogaol can effectively complement L-dopa by improving non-motor dysfunction and restoring dopaminergic neurons via suppressing neuroinflammation.

Background: Limited evidence exists on the role of depression in the risk of developing stroke and other cardiovascular outcomes in patients who have undergone percutaneous coronary interventions (PCI). We investigated this relationship with data from the Korean National Health Insurance Service database., Methods: Our nationwide retrospective cohort study included 164,198 patients who had undergone PCI between 2010 and 2017. Depression was defined with the ICD-10 codes recorded prior to the PCI. The primary outcome was a new-onset stroke following the PCI. Secondary outcomes included PCI with myocardial infarction (MI), revascularization (PCI or coronary artery bypass grafting), and all-cause mortality. A multivariable Cox proportional hazards regression analysis was used to calculate adjusted hazard ratios (aHR) and 95% confidence intervals (CI), adjusting for potential confounders, including sociodemographic and lifestyle factors, comorbidities, and MI at the index PCI., Results: Over a median follow-up of 5.0 years, acute stroke occurred in 5.7% of patients with pre-existing depression (17.4% of the study population), compared to 3.5% of those without depression. Depression was associated with a 27% increased risk of acute stroke (aHR 1.27, 95% CI 1.20-1.35). Additionally, depression was linked with a 25% elevated risk of all-cause death (aHR 1.25, 95% CI, 1.21-1.29) and an 8% increased risk of revascularization (aHR 1.08, 95% CI 1.04-1.11). The associations with the risk of stroke and all-cause mortality were stronger in patients under 65 years., Conclusions: Our findings suggest that pre-existing depression may increase the risk of stroke and all-cause mortality following PCI, particularly in patients under 65 years. Additionally, depression was significantly associated with an increased need for revascularization. This underscores the potential benefits of managing depression to reduce stroke risk and overall cardiovascular outcomes following PCI., (© 2024 The Association for the Publication of the Journal of Internal Medicine.)

Background and Purpose: To date, only a few small studies have attempted deep learning-based automatic segmentation of white matter hyperintensity (WMH) lesions in patients with cerebral infarction, which is complicated because stroke-related lesions can obscure WMH borders. We developed and validated deep learning algorithms to segment WMH lesions accurately in patients with cerebral infarction, using multisite datasets involving 8,421 patients with acute ischemic stroke., Materials and Methods: We included 8,421 stroke patients from 9 centers in Korea. 2D UNet and SE-Unet models were trained using 2,408 FLAIR MRI from 3 hospitals and validated using 6,013 FLAIR MRIs from 6 hospitals. WMH segmentation performance was assessed by calculating DSC, correlation coefficient, and concordance correlation coefficient compared to a human-segmented gold standard. In addition, we obtained an uncertainty index that represents overall ambiguity in the voxel classification for WMH segmentation in each patient based on the Kullback-Leibler divergence., Results: In the training dataset, the mean age was 67.4±13.0 years and 60.4% were men. The mean (95% CI) DSCs for Unet in internal testing and external validation were respectively 0.659 (0.649-0.669) and 0.710 (0.707-0.714), which were slightly lower than the reliability between humans (DSC=0.744; 95% CI=0.738-0.751; P=.031). Compared with the Unet, the SE-Unet demonstrated better performance, achieving a mean DSC of 0.675 (0.666-0.685; P<.001) in the internal testing and 0.722 (0.719-0.726; P<.001) in the external validation; moreover, it achieved high DSC values (ranging from 0.672 to 0.744) across multiple validation datasets. We observed a significant correlation between WMH volumes that were segmented automatically and manually for the Unet (r=0.917, P<.0001) and even stronger for the SE-Unet (r=0.933, P<.0001). The SE-Unet also attained a high concordance correlation coefficient (ranging from 0.841 to 0.956) in external test datasets. In addition, the uncertainty indices in the majority of patients (86%) in the external datasets were below 0.35, with an average DSC of 0.744 in these patients., Conclusions: We developed and validated deep learning algorithms to segment WMH in patients with acute cerebral infarction using the largest-ever MRI datasets. In addition, we showed that the uncertainty index can be used to identify cases where automatic WMH segmentation is less accurate and requires human review., Abbreviations: WMH = white matter hyperintensity; CNN = convolutional neural networks; SE = squeeze-and-excitation; KL = Kullback-Leibler; ReLU = rectified linear unit; LKW = last known well; mRS = modified Rankin Scale; NIHSS = National Institute of Health Stroke Scale; LAA = large artery atherosclerosis; SVO = small vessel occlusion; CE = cardioembolism., (© 2024 by American Journal of Neuroradiology.)

Background: Alzheimer's disease (AD) is a common type of dementia characterized by amyloid-β (Aβ) accumulation, lysosomal dysfunction, and tau hyperphosphorylation, leading to neurite dystrophy and memory loss. This study aimed to investigate whether Rhei Undulati Rhizoma (RUR), which has been reported to have anti-neuroinflammatory effect, attenuates Aβ-induced memory impairment, neuritic dystrophy, and tau hyperphosphorylation, and to reveal its mode of action., Methods: Five-month-old 5xFAD mice received RUR (50 mg/kg) orally for 2 months. The Y-maze test was used to assess working memory. After behavioral testing, brain tissue was analyzed using thioflavin S staining, western blotting, and immunofluorescence staining to investigate the mode of action of RUR. To confirm whether RUR directly reduces Aβ aggregation, a thioflavin T assay and dot blot were performed after incubating Aβ with RUR., Results: RUR administration attenuated the Aβ-induced memory impairment in 5xFAD mice. Furthermore, decreased accumulation of Aβ was observed in the hippocampus of the RUR-treated 5xFAD group compare to the vehicle-treated 5xFAD group. Moreover, RUR reduced the dystrophic neurites (DNs) that accumulate impaired endolysosomal organelles around Aβ. In particular, RUR treatment downregulated the expression of β-site amyloid precursor protein cleaving enzyme 1 and the hyperphosphorylation of tau within DNs. Additionally, RUR directly suppressed the aggregation of Aβ, and eliminated Aβ oligomers in vitro., Conclusions: This study showed that RUR could attenuate Aβ-induced pathology and directly regulate the aggregation of Aβ. These results suggest that RUR could be an efficient material for AD treatment through Aβ regulation., (© 2024. The Author(s).)

Food processing industries commonly employ organic acids (OAAs) to determine bacterial contamination in acidified and fermented foods. OAAs are believed to possess potent antimicrobial properties by permeating cell membranes, altering proton and anion concentrations in the cytoplasm due to their lipophilic undissociated forms. The bacteriostatic or bactericidal effects of OAAs are influenced by various factors including microbial physiology, environmental pH, and acid dissociation ratios. Despite their utility, the precise mechanisms underlying OAA-mediated inhibition of pathogenic bacteria remain incompletely understood. Therefore, the objectives of this review are to compile a selected area of researches that focus on the current propensity of different OAAs for inactivating food-borne pathogens, and then to present a theoretical insight on the use of OAAs to prevent and control pathogenic bacteria present in acidic/acidified foods and their mode of mechanisms., Competing Interests: Conflict of interestThe authors declare no conflict of interests., (© The Korean Society of Food Science and Technology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Mitochondria are essential organelles for cell survival that manage the cellular energy supply by producing ATP. Mitochondrial dysfunction is associated with various human diseases, including metabolic syndromes, aging, and neurodegenerative diseases. Among the diseases related to mitochondrial dysfunction, Parkinson's disease (PD) is the second most common neurodegenerative disease and is characterized by dopaminergic neuronal loss and neuroinflammation. Recently, it was reported that mitochondrial transfer between cells occurred naturally and that exogenous mitochondrial transplantation was beneficial for treating mitochondrial dysfunction. The current study aimed to investigate the therapeutic effect of mitochondrial transfer on PD in vitro and in vivo. The results showed that PN-101 mitochondria isolated from human mesenchymal stem cells exhibited a neuroprotective effect against 1-methyl-4-phenylpyridinium, 6-hydroxydopamine and rotenone in dopaminergic cells and ameliorated dopaminergic neuronal loss in the brains of C57BL/6J mice injected 30 ​mg/kg of methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intraperitoneally. In addition, PN-101 exhibited anti-inflammatory effects by reducing the expression of pro-inflammatory cytokines in microglial cells and suppressing microglial activation in the striatum. Furthermore, intravenous mitochondrial treatment was associated with behavioral improvements during the pole test and rotarod test in the MPTP-induced PD mice. These dual effects of neuroprotection and anti-neuroinflammation support the potential for mitochondrial transplantation as a novel therapeutic strategy for PD., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Shin-Hye Yu reports a relationship with Paean Biotechnology that includes: employment. Yujin Kim reports a relationship with Paean Biotechnology that includes: employment. Young Cheol Kang reports a relationship with Paean Biotechnology that includes: equity or stocks. Kyuboem Han reports a relationship with Paean Biotechnology that includes: employment. Hong Kyu Lee reports a relationship with Paean Biotechnology that includes: employment. Chun-Hyung Kim reports a relationship with Paean Biotechnology that includes: employment. 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 Inc. All rights reserved.)

Aluminum-incorporated medium-manganese steel (MMnS) has potential for lightweight transport applications owing to its impressive mechanical properties. Increasing the austenite volume fraction and making microstructural changes are key to manufacturing MMnS. However, the grain boundary character and strain distribution of intercritically annealed low-density MMnS have not been extensively scrutinized, and the effects of crystallographic texture orientation on tensile properties remain ambiguous. Therefore, in this study, the microstructure, microtexture, strain distribution, and grain boundary characteristics of a hot-rolled medium-Mn steel (Fe-0.2 C-4.3 Al-9.4 Mn (wt%)) were investigated after intercritical annealing (IA) at 750, 800, or 850 °C for 1 h. The results show that the 800 °C annealed sample exhibited the highest austenite volume fraction among the specimens (60%). The duplex microstructure comprised lath-type γ-austenite, fine α-ferrite, and coarse δ-ferrite. As the IA temperature increased, the body-centered cubic phase orientation shifted from <001> to <111>. At higher temperatures, the face-centered cubic phase was oriented in directions ranging from <101> to <111>, and the sums of the fractions of high-angle grain boundaries and coincidence-site-lattice special boundaries were significantly increased. The 800 °C annealed sample with a high austenite content and strong γ-fiber {111}//RD orientation demonstrated a noteworthy tensile strength (1095 MPa) and tensile elongation (30%).

Background: According to international pediatric urinary tract infection (UTI) guidelines, selecting ampicillin/sulbactam or amoxicillin/clavulanate is recommended as the first-line treatment for pediatric UTI. In Korea, elevated resistance to ampicillin and ampicillin/sulbactam has resulted in the widespread use of third-generation cephalosporins for treating pediatric UTIs. This study aims to compare the efficacy of piperacillin-tazobactam (TZP) and cefotaxime (CTX) as first-line treatments in hospitalized children with UTIs., Materials and Methods: The study, conducted at Jeju National University Hospital, retrospectively analyzed medical records of children hospitalized for febrile UTIs between 2014 and 2017. UTI diagnosis included unexplained fever, abnormal urinalysis, and the presence of significant uropathogens. Treatment responses, recurrence, and antimicrobial susceptibility were assessed., Results: Out of 323 patients, 220 met the inclusion criteria. Demographics and clinical characteristics were similar between TZP and CTX groups. For children aged ≥3 months, no significant differences were found in treatment responses and recurrence. Extended-spectrum beta-lactamase (ESBL)-positive strains were associated with recurrence in those <3 months., Conclusion: In Korea, escalating resistance to empirical antibiotics has led to the adoption of broad-spectrum empirical treatment. TZP emerged as a viable alternative to CTX for hospitalized children aged ≥3 months with UTIs. Consideration of ESBL-positive strains and individualized approaches for those <3 months are crucial., Competing Interests: No conflict of interest., (© 2024 by The Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, The Korean Society for AIDS, and Korean Society of Pediatric Infectious Diseases.)

Background: This study aimed to evaluate the efficacy and safety of anticoagulants (AC) and antiplatelets (APT) in patients with recent small subcortical infarctions (RSSI) and atrial fibrillation (AF)., Methods: We utilized a prospective multicenter stroke registry database to identify patients with RSSI with a concurrent diagnosis of AF. Propensity score matching analysis was used to balance baseline differences among the AC-only, APT-only, and their combination groups. The main outcomes of interest were time to occurrence of minor and major bleeding, stroke recurrence, and all-cause mortality. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for each outcome were calculated using the multivariable Cox proportional hazard regression analysis., Results: Of the 404 eligible patients, 28.2% received APT only, 53.0% received AC only, and 18.9% received a combination of both. Notable differences were observed between these groups in terms of the 1-year stroke recurrence (APT, 32.5%; AC, 5.6%; APT + AC, 9.2%) and all-cause mortality (APT, 21.9%; AC, 6.1%; APT + AC, 14.5%), whereas the rates of bleeding events were comparable. The multivariable analysis indicated a significant association of AC alone with reduced risks of severe bleeding, stroke recurrence, and all-cause mortality compared with APT alone (aHR 0.64, 95% CI 0.41-0.98; aHR 0.11, 95% CI 0.06-0.22; aHR 0.22, 95% CI 0.11-0.44, respectively). The combination group showed a reduced risk of stroke recurrence compared to APT alone (aHR 0.19, 95% CI 0.08-0.46). These findings remained consistent with the propensity score-matched analysis., Conclusion: AC showed better clinical outcomes than APT in patients with RSSI and AF. Additionally, combination therapy with AC and APT was associated with a lower risk of stroke recurrence than APT alone., 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.

Objective: This study aimed to investigate the characteristics and epidemiological trends of pediatric injuries among patients visiting emergency departments (EDs) on Jeju Island., Method: Employing a community-level serial cross-sectional analysis, we targeted pediatric patients aged 18 years or younger who visited EDs for injuries over a ten-year period. The data, sourced from the Jeju Injury Surveillance System (JISS), facilitated a comprehensive examination of injury characteristics and epidemiological trends. This included an evaluation of the annual incidence and overall trends in pediatric injury cases., Results: The study found toddlers (42.5% of cases) to be the most frequently injured age group. Males were more prone to injuries, with a male-to-female ratio of 1.7:1. Injuries among visitors accounted for 17.3% of cases, with a seasonal spike in Summer, evenings and weekends. Most incidents occurred at home, predominantly accidental in nature, with adolescents more likely to require EMS services. The common mechanisms of injuries were blunt force (49.2%), slips/falls (22.0%), and motor vehicle collisions (13.2%), leading to bruises, cuts, and sprains. Over the decade, a general increase in pediatric injuries was observed. Accidental injuries initially surged but later stabilized, while self-harm/suicide and assault/violence injuries showed a concerning upward trend. Age-specific analysis revealed increasing trends in infants and adolescents., Conclusion: The study underscores the crucial need for targeted injury prevention and resource allocation strategies, particularly for high-risk groups and times, to effectively mitigate pediatric trauma on Jeju Island.

Background: Recent clinical trials established the benefit of dual antiplatelet therapy with aspirin and clopidogrel (DAPT-AC) in early-presenting patients with minor ischemic stroke. However, the impact of these trials over time on the use and outcomes of DAPT-AC among the patients with nonminor or late-presenting stroke who do not meet the eligibility criteria of these trials has not been delineated., Methods and Results: In a multicenter stroke registry, this study examined yearly changes from April 2008 to August 2022 in DAPT-AC use for stroke patients ineligible for CHANCE/POINT (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events/Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) clinical trials due to National Institutes of Health Stroke Scale >4 or late arrival beyond 24 hours of onset. A total of 32 118 patients (age, 68.1±13.1 years; male, 58.5%) with National Institutes of Health Stroke Scale of 4 (interquartile range, 1-7) were analyzed. In 2008, DAPT-AC was used in 33.0%, other antiplatelets in 62.7%, and no antiplatelet in 4.3%. The frequency of DAPT-AC was relatively unchanged through 2013, when the CHANCE trial was published, and then increased steadily, reaching 78% in 2022, while other antiplatelets decreased to 17.8% in 2022 ( P trend <0.001). From 2011 to 2022, clinical outcomes nonsignificantly improved, with an average relative risk reduction of 2%/y for the composite of stroke, myocardial infarction, and all-cause mortality, both among patients treated with DAPT-AC and patients treated with other antiplatelets., Conclusions: Use of DAPT-AC in stroke patients with stroke ineligible for recent DAPT clinical trials increased markedly and steadily after CHANCE publication in 2013, reaching deployment in nearly 4 of every 5 patients by 2022. The secondary prevention in patients with ischemic stroke seems to be gradually improving, possibly due to the enhancement of risk factor control.

Background: Late hospital arrival keeps patients with stroke from receiving recanalization therapy and is associated with poor outcomes. This study used a nationwide acute stroke registry to investigate the trends and regional disparities in prehospital delay and analyze the significant factors associated with late arrivals., Methods: Patients with acute ischemic stroke or transient ischemic attack between January 2012 and December 2021 were included. The prehospital delay was identified, and its regional disparity was evaluated using the Gini coefficient for nine administrative regions. Multivariate models were used to identify factors significantly associated with prehospital delays of >4.5 h., Results: A total of 144,014 patients from 61 hospitals were included. The median prehospital delay was 460 min (interquartile range, 116-1912), and only 36.8% of patients arrived at hospitals within 4.5 h. Long prehospital delays and high regional inequality (Gini coefficient > 0.3) persisted throughout the observation period. After adjusting for confounders, age > 65 years old (adjusted odds ratio [aOR] = 1.23; 95% confidence interval [CI], 1.19-1.27), female sex (aOR = 1.09; 95% CI, 1.05-1.13), hypertension (aOR = 1.12; 95% CI, 1.08-1.16), diabetes mellitus (aOR = 1.38; 95% CI, 1.33-1.43), smoking (aOR = 1.15, 95% CI, 1.11-1.20), premorbid disability (aOR = 1.44; 95% CI, 1.37-1.52), and mild stroke severity (aOR = 1.55; 95% CI, 1.50-1.61) were found to independently predict prehospital delays of >4.5 h., Conclusion: Prehospital delays were lengthy and had not improved in Korea, and there was a high regional disparity. To overcome these inequalities, a deeper understanding of regional characteristics and further research is warranted to address the vulnerabilities identified., 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.

Immune checkpoint blockade (ICB) with PD-1/PD-L1 inhibition has revolutionized the treatment of non-small cell lung cancer (NSCLC). Durable responses, however, are observed only in a subpopulation of patients. Defective antigen presentation and an immunosuppressive tumor microenvironment (TME) can lead to deficient T cell recruitment and ICB resistance. We evaluate intratumoral (IT) vaccination with CXCL9- and CXCL10-engineered dendritic cells (CXCL9/10-DC) as a strategy to overcome resistance. IT CXCL9/10-DC leads to enhanced T cell infiltration and activation in the TME and tumor inhibition in murine NSCLC models. The antitumor efficacy of IT CXCL9/10-DC is dependent on CD4 + and CD8 + T cells, as well as CXCR3-dependent T cell trafficking from the lymph node. IT CXCL9/10-DC, in combination with ICB, overcomes resistance and establishes systemic tumor-specific immunity in murine models. These studies provide a mechanistic understanding of CXCL9/10-DC-mediated host immune activation and support clinical translation of IT CXCL9/10-DC to augment ICB efficacy in NSCLC., Competing Interests: Declaration of interests S.M.D. is a scientific advisory board member for EarlyDiagnostics Inc. and LungLife AI; he has received research funding from Johnson & Johnson and Novartis. R.J.L., R.S.-R., B.L., and S.M.D. are the inventors of a pending patent., (Published by Elsevier Inc.)

Objective: To describe our modifications to the submental island flap (SMIF) in a case series that demonstrates improved reproducibility, shortened length of stay (LOS), and reduced utilization of hospital resources., Study Design: This retrospective case series with chart review included adult patients who underwent resection of malignant or benign tumors resulting in lateral facial, parotid, or temporal bone defects, which were reconstructed with SMIF., Setting: A tertiary-care academic referral center., Methods: Retrospective case series included all adult patients who underwent SMIF reconstruction between March 2020 and August 2021. Patient demographic and clinical data were collected. Primary outcomes were measures of hospital utilization including duration of surgery, LOS, and postoperative outcomes., Results: Twenty-eight patients were included with a mean age of 71.7 years. Eighty percent were male. All patients underwent parotidectomy, and the mean operative time was 347 minutes. The median LOS was 2.5 days (range 0-16 days). Seventy-five percent of the flaps drained into the internal jugular vein, and 25% drained into the external jugular vein. No patients required reoperation or readmission. All flaps survived., Conclusion: SMIFs are a safe and effective option for reconstruction of lateral facial, parotid, and temporal bone defects. Compared to free flap reconstruction, SMIFs offer reduced length of surgery, decreased use of health care resources, and lower rate of reoperation. As health care resource allocation is increasingly important, the SMIF offers an excellent alternative to free flap reconstruction of lateral defects., Competing Interests: Nicole C. Schmitt discloses research funding from Astex Pharmaceuticals and consulting for Sensorion and Checkpoint Surgical (unrelated to this work). The other authors (Melissa S. Oh, Nikhil T. Vettikattu, Harry Michael Baddour, Jennifer H. Gross, Brian J. Boyce, Mihir R. Patel, Clementino Arturo Solares, Azeem S. Kaka) declare that they have no conflicts of interest., (© 2024 The Authors. OTO Open published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Context: Neurocognitive testing is a critical tool in the management of sport-related concussions. Adversity during childhood and adolescence affects cognitive tasks, behavioral outcomes, and academic performance. Adversity may be important in baseline concussion test validity as well; however, the influence of these experiences is not well understood., Objective: To examine the relationship between individual-level experiences of adversity and baseline test validity of Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT). We hypothesized that experiences of poverty, maltreatment, or extreme neighborhood deprivation would be associated with lower odds of baseline test validity., Design: Case-control study., Setting: Cuyahoga County, Ohio., Patients or Other Participants: A total of 6495 student-athletes born from 1995 through 2005 who completed a baseline ImPACT test between 10 and 18 years old and were identified in the Child-Household Integrated Longitudinal Data system, a comprehensive data system with demographic and social service usage outcomes for children in Cuyahoga County, Ohio., Main Outcome Measure(s): Baseline concussion test validity was determined using the ImPACT built-in validity measure. Experiences of adversity during the sensitive developmental periods of early childhood and adolescence were key independent variables., Results: Our findings suggested that social mobility may play an important role in baseline validity. Youth with upward social mobility (ie, poverty or neighborhood deprivation in early childhood only) were not different from youth without such experiences (odds ratio [OR] = 0.91, P = .74). Youth with persistent adversity across childhood or downward social mobility (ie, poverty or high neighborhood deprivation in adolescence only) had 50% to 72% lower odds of achieving a valid baseline test (persistent poverty, OR = 0.59, P = .05; adolescent poverty only, OR = 0.50, P = .004; adolescent neighborhood deprivation only, OR = 0.28, P < .001). Maltreatment had no significant effect on test validity., Conclusions: These findings indicated that certain patterns of adversity may predispose youth to invalid baseline testing scores, potentially increasing their risk of inappropriate injury management and poor outcomes., (© by the National Athletic Trainers’ Association, Inc.)