Guanylate binding protein 5 triggers NF-κB activation to foster radioresistance, metastatic progression and PD-L1 expression in oral squamous cell carcinoma.

Radioresistance and metastasis are critical issues in managing oral squamous cell carcinoma (OSCC). Although immune checkpoint inhibitors (ICIs) has been recommended to treat OSCC, lacking useful biomarkers limited their anti-cancer effectiveness. We found that guanylate binding protein 5 (GBP5) is upregulated in primary tumors and associates with radioresistance in OSCC. GBP5 expression causally associated with cellular radioresistance and migration ability in the OSCC cell variants. GBP5 upregulation was examined to be correlated with NF-κB activation and programmed cell death-ligand 1 (PD-L1) elevation in OSCC samples. GBP5 knockdown was mitigated, but overexpression enhanced, NF-κB activity and PD-L1 expression in the OSCC cells. NF-κB inhibition by SN50 dramatically suppressed the GBP5-forested irradiation resistance, cellular migration ability and PD-L1 expression in OSCC cells. Importantly, GBP5 upregulation predicted a favorable outcome in cancer patients received ICI treatment. Our findings provide GBP5 as a useful biomarker to predict the anti-OSCC effectiveness of irradiation and ICIs.

AIM2 promotes irradiation resistance, migration ability and PD-L1 expression through STAT1/NF-κB activation in oral squamous cell carcinoma.

BACKGROUND: Radioresistance and lymph node metastasis are common phenotypes of refractory oral squamous cell carcinoma (OSCC). As a result, understanding the mechanism for radioresistance and metastatic progression is urgently needed for the precise management of refractory OSCC. Recently, immunotherapies, e.g. immune checkpoint inhibitors (ICIs), were employed to treat refractory OSCC; however, the lack of predictive biomarkers still limited their therapeutic effectiveness. METHODS: The Cancer Genome Atlas (TCGA)/Gene Expression Omnibus (GEO) databases and RT-PCR analysis were used to determine absent in melanoma 2 (AIM2) expression in OSCC samples. Colony-forming assay and trans-well cultivation was established for estimating AIM2 function in modulating the irradiation resistance and migration ability of OSCC cells, respectively. RT-PCR, Western blot and flow-cytometric analyses were performed to examine AIM2 effects on the expression of programmed death-ligand 1 (PD-L1) expression. Luciferase-based reporter assay and site-directed mutagenesis were employed to determine the transcriptional regulatory activity of Signal Transducer and Activator of Transcription 1 (STAT1) and NF-κB towards the AIM2-triggered PD-L1 expression. RESULTS: Here, we found that AIM2 is extensively upregulated in primary tumors compared to the normal adjacent tissues and acts as a poor prognostic marker in OSCC. AIM2 knockdown mitigated, but overexpression promoted, radioresistance, migration and PD-L1 expression via modulating the activity of STAT1/NF-κB in OSCC cell variants. AIM2 upregulation significantly predicted a favorable response in patients receiving ICI treatments. CONCLUSIONS: Our data unveil AIM2 as a critical factor for promoting radioresistance, metastasis and PD-L1 expression and as a potential biomarker for predicting ICI effectiveness on the refractory OSCC.

Psychometric and structural properties of the traditional Chinese version of the sleep condition indicator for patients undergoing hemodialysis.

PURPOSE: Insomnia is a prevalent sleep disorder among patients undergoing hemodialysis for chronic kidney disease. This study aimed to translate the sleep condition indicator (SCI), an insomnia screening tool based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), into a traditional Chinese version (SCI-TC) and evaluate the reliability and validity of this version for patients undergoing hemodialysis. METHODS: This cross-sectional study conducted from November 2022 to June 2023 involved 200 patients on hemodialysis (mean age, 65.56 years; 61.5% men). Participants completed a series of questionnaires, with insomnia diagnosed according to DSM-5 criteria as the gold standard. A receiver operating characteristic (ROC) curve analysis was conducted to examine the sensitivity and specificity of the SCI-TC. RESULTS: According to the DSM-5 criteria, 38% of the participants had insomnia. Cronbach's alpha for the SCI-TC was 0.92. The SCI-TC exhibited a good fit as a two-factor model, and its scores were significantly associated with those of the traditional Chinese versions of the Insomnia Severity Index, Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, EuroQol 5-Dimensions scale, and EuroQol Visual Analogue Scale (r = - 0.94, - 0.53, - 0.38, 0.27, and 0.30, respectively; all p < 0.05). The ROC curve analysis revealed an optimal cutoff of 16 points, with the sensitivity, specificity, and area under curve of 88.2%, 84.7%, and 0.91(95% confidence interval, 0.87-0.95), respectively. CONCLUSION: The SCI-TC demonstrates robust reliability and validity in detecting insomnia among patients undergoing hemodialysis. These findings suggest that health-care providers should considering using the SCI as an easy-to-use tool for the timely detection of insomnia in this population.

AIM2 upregulation promotes metastatic progression and PD-L1 expression in lung adenocarcinoma.

Cancer metastasis leading to the dysfunction of invaded organs is the main cause of the reduced survival rates in lung cancer patients. However, the molecular mechanism for lung cancer metastasis remains unclear. Recently, the increased activity of inflammasome appeared to correlate with the metastatic progression and immunosuppressive ability of various cancer types. Our results showed that the mRNA levels of absence in melanoma 2 (AIM2), one of the inflammasome members, are extensively upregulated in primary tumors compared with normal tissues derived from the TCGA lung adenocarcinoma (LUAD) database. Moreover, Kaplan-Meier analysis demonstrated that a higher mRNA level of AIM2 refers to a poor prognosis in LUAD patients. Particularly, AIM2 upregulation is closely correlated with smoking history and the absence of EGFR/KRAS/ALK mutations in LUAD. We further showed that the endogenous mRNA levels of AIM2 are causally associated with the metastatic potentials of the tested LUAD cell lines. AIM2 knockdown suppressed but overexpression promoted the migration ability and lung colony-forming ability of tested LUAD cells. In addition, we found that AIM2 upregulation is closely associated with an increased level of immune checkpoint gene set, as well as programmed cell death-ligand 1 (PD-L1) transcript, in TCGA LUAD samples. AIM2 knockdown predominantly repressed but overexpression enhanced PD-L1 expression via altering the activity of PD-L1 transcriptional regulators NF-κB/STAT1 in LUAD cells. Our results not only provide a possible mechanism underlying the AIM2-promoted metastatic progression and immune evasion of LUAD but also offer a new strategy for combating metastatic/immunosuppressive LUAD via targeting AIM2 activity.

NEDD8 promotes radioresistance via triggering autophagy formation and serves as a novel prognostic marker in oral squamous cell carcinoma.

BACKGROUND: Radiotherapy is the first-line regimen for treating oral squamous cell carcinoma (OSCC) in current clinics. However, the development of therapeutic resistance impacts the anticancer efficacy of irradiation in a subpopulation of OSCC patients. As a result, discovering a valuable biomarker to predict radiotherapeutic effectiveness and uncovering the molecular mechanism for radioresistance are clinical issues in OSCC. METHODS: Three OSCC cohorts from The Cancer Genome Atlas (TCGA), GSE42743 dataset and Taipei Medical University Biobank were enrolled to examine the transcriptional levels and prognostic significance of neuronal precursor cell-expressed developmentally downregulated protein 8 (NEDD8). Gene set enrichment analysis (GSEA) was utilized to predict the critical pathways underlying radioresistance in OSCC. The colony-forming assay was used to estimate the consequences of irradiation sensitivity after the inhibition or activation of the NEDD8-autophagy axis in OSCC cells. RESULTS: NEDD8 upregulation was extensively found in primary tumors compared to normal adjacent tissues and potentially served as a predictive marker for the therapeutic effectiveness of irradiation in OSCC patients. NEDD8 knockdown enhanced radiosensitivity but NEDD8 overexpression reduced it in OSCC cell lines. The inclusion of MLN4924, a pharmaceutical inhibitor for NEDD8-activating enzyme, dose-dependently restored the cellular sensitivity to irradiation treatment in irradiation-insensitive OSCC cells. Computational simulation by GSEA software and cell-based analyses revealed that NEDD8 upregulation suppresses Akt/mTOR activity to initiate autophagy formation and ultimately confers radioresistance to OSCC cells. CONCLUSION: These findings not only identify NEDD8 as a valuable biomarker to predict the efficacy of irradiation but also offer a novel strategy to overcome radioresistance via targeting NEDD8-mediated protein neddylation in OSCC.

Myalgia! Where does it come from?

Myalgia (also called muscle pain or muscle ache) is a symptom associated with many diseases, including fibromyalgia, neurodegenerative diseases, degenerative spine diseases, etc. Myalgia is a major medical problem affecting 60~85% of the population (lifetime prevalence). However, our understanding of chronic myalgia is still limited and effective treatment for intractable myalgia like fibromyalgia is still lacking. Although multifactorial, one known source of muscle pain is tissue acidosis. Experimental muscle pain can be induced by the intramuscular infusion of a buffered acidic solution in humans. As well, animal studies have revealed that acidic infusion activates chemosensitive nociceptors via the proton-sensing ion channels and receptors. Intriguingly, acid signaling in muscle afferents is promiscuous and could be either pro-nociceptive or antinociceptive, so we have coined the term sngception to describe the somatosensory function of acid sensation. Recent single-cell RNAseq studies have shown proton-sensing ion channels and receptors are expressed in all subpopulations of the somatosensory neurons, including nociceptors and non-nociceptive mechanoreceptors. Here, we address how the acid signaling is integrated in muscle afferents and why muscle pain can be chronic and intractable in mouse models of fibromyalgia. Besides acidosis, we have recently found oxidative stress can be another factor to activate proton-sensing ion channels and thus trigger fibromyalgia-like pain in mice. Together, understanding how the acid signaling works in muscle afferents will provide novel therapeutic strategies for myalgia.

Activation of peripheral TRPM8 mitigates ischemic stroke by topically applied menthol.

BACKGROUND: No reports exist as to neuroprotective effects associated with topical activation of transient receptor potential melastatin 8 (TRPM8), a noted cold receptor. In the present study, we identified whether activating peripheral TRPM8 can be an adjuvant therapy for ischemic stroke. METHODS: Menthol, an agonist of TRPM8, was applied orally or topically to all paws or back of the mouse after middle cerebral artery occlusion (MCAO). We used Trpm8 gene knockout (Trpm8-/-) mice or TRPM8 antagonist and lidocaine to validate the roles of TRPM8 and peripheral nerve conduction in menthol against ischemic stroke. RESULTS: Application of menthol 16% to paw derma attenuated infarct volumes and ameliorated sensorimotor deficits in stroke mice induced by MCAO. The benefits of topically applied menthol were associated with reductions in oxidative stress, neuroinflammation and infiltration of monocytes and macrophages in ischemic brains. Antagonizing TRPM8 or Trpm8 knockout dulls the neuroprotective effects of topically application of menthol against MCAO. Immunohistochemistry analyses revealed significantly higher TRPM8 expression in skin tissue samples obtained from the paws compared with skin from the backs, which was reflected by significantly smaller infarct lesion volumes and better sensorimotor function in mice treated with menthol on the paws compared with the back. Blocking conduction of peripheral nerve in the four paws reversed the neuroprotective effects of topical menthol administrated to paws. On the other hand, oral menthol dosing did not assist with recovery from MCAO in our study. CONCLUSION: Our results suggested that activation of peripheral TRPM8 expressed in the derma tissue of limbs with sufficient concentration of menthol is beneficial to stroke recovery. Topical application of menthol on hands and feet could be a novel and simple-to-use therapeutic strategy for stroke patients.

Benefits of Caregiver Counseling in Patients with Dementia: A Retrospective Observational Study.

INTRODUCTION: Patients with dementia have a 1.42 times higher risk of hospitalization than those without. Preparing and educating caregivers by counseling may attenuate the frequency of hospitalization and the financial burden on the health-care system. We conducted a retrospective observational study to verify whether caregiver counseling would benefit patients with mild cognitive impairment (MCI) or dementia. METHODS: The primary caregivers of patients with MCI or dementia at our Dementia Center from January 2017 to December 2018 were included in this study. Of the 532 caregivers who received counseling on caregiving for patients with dementia, 350 with complete data were included. The incidences of the patients' emergency department visits, hospitalizations, and durations of hospitalizations in 2 years prior to and after their caregivers received counseling were compared. A paired t test was used to test the frequency of patients' hospitalizations and emergency visits before and after counseling, and a p value of less than 0.05 was considered significant. RESULTS: The incidence of emergency visits (before counseling: 0.67 times/year, standard deviation [SD] = 0.823; after counseling: 0.25 times/year, SD = 0.549; p < 0.001) and hospitalizations (before counseling: 1.104 times/year, SD = 0.882; after counseling: 0.719 times/year, SD = 0.642; p < 0.001) decreased significantly after caregivers received counseling. The durations of hospitalization before and after counseling were 9.74 (SD = 6.940) days and 9.23 (SD = 6.908) days, respectively (p = 0.136). CONCLUSION: Counseling for caregivers of patients with MCI or dementia can significantly decrease the incidences of patients' emergency visits and hospitalizations but not durations of hospitalization. In multifaceted disease like dementia, counseling for caregivers is beneficial and reduces the burden on the health-care system. Further large-scale studies are warranted to verify this finding.

Clinical Spectrum of Positional Vertigo in an Outpatient Setting.

OBJECTIVES: To explore the clinical spectrum of positional vertigo (PV) and to study the causes of PV with atypical positional nystagmus (PN) and PV without PN. DESIGN: We retrospectively analyzed the registry (2425 cases) in a university hospital. Patients who actively reported PV as their main dizziness pattern were included. Candidates were divided into three groups according to their PN: (1) benign paroxysmal PV (BPPV); (2) PV with atypical PN; and (3) PV without PN. The diagnoses and reported symptoms in each group were analyzed. RESULTS: PV was the most commonly (n = 518, 28.3%) reported pattern in the registry. The two most common diagnoses of PV were BPPV (n = 146, 29.2%) and vestibular migraine (VM; n = 137, 27.4%). Fifty-seven (11.4%) patients had PV with atypical PN, the majority of which was caused by VM. Moreover, 297 (59.4%) patients had PV without PN. The two main diagnoses in this group were VM and functional dizziness, although the cause remained uncertain in 23.9% of the cases of PV without PN. The odds ratio of VM was 3.95 in patients with PV who reported headaches. CONCLUSIONS: PV is the most common self-reported dizziness pattern and is predominantly caused by BPPV and VM. VM is the most common cause of PV with atypical PN and PV without PN. Clinicians often erroneously assume the presence of PN in those with PV. Managing PV without PN can be challenging because of the uncertainty surrounding this phenomenon. Structured patient-oriented questionnaires assist clinicians in making timely diagnoses and adjusting treatment goals accordingly.

Association of rs2651899 Polymorphism in the Positive Regulatory Domain 16 and Common Migraine Subtypes: A Meta-Analysis.

BACKGROUND: Migraine is a neurovascular disease with recurrent headache attacks. A polymorphism (rs2651899) of the PRDM16 gene, which is associated with migraine, was identified in recent genome-wide association studies. The potential role of the PRDM16 rs2651899 polymorphism in migraine is still unknown. Therefore, we conducted this systematic review and meta-analysis to examine this issue. METHODS: We performed a comprehensive literature search of the PubMed, Embase, and Google Scholar databases to identify eligible studies published before October 2018. Individual odds ratio and 95% confidence interval was used to estimate the pooled strength of the association between the PRDM16 rs2651899 polymorphism and common migraine subtypes, including migraine with aura (MA) and migraine without aura (MO). RESULTS: Six studies with 2853 cases and 9319 controls that fulfilled the inclusion and exclusion criteria were selected for this meta-analysis. Of the 6 included studies, 4 studies had available data for MWA and another 4 studies had data for MWoA. Overall, significant migraine risks of 1.257, 1.305, and 1.419 were found under allele model (C vs T), dominant model (C/C+T/C vs T/T), and recessive model (C/C vs T/C+T/T), respectively. In the recessive model, significantly increased risks of 1.454 and 1.546 were found for MA and MO, respectively. CONCLUSION: Our major findings suggest that PRDM16 rs2651899 polymorphism is associated with the risk of migraine. Furthermore, we found that PRDM16 rs2651899 polymorphism is significantly related to common migraine subtypes (MA and MO).

The Association of Apolipoprotein E Allele 4 Polymorphism with the Recovery of Sleep Disturbance after Mild Traumatic Brain Injury.

PURPOSE: Mild traumatic brain injury (mTBI) is a major public health concern. The apolipoprotein E (APOE) gene contains three polymorphisms, and the APOE4 polymorphism may affect several physiological states, such as the recovery from mTBI as well as sleep. This study aims to investigate the association between APOE4 with the recovery of sleep disturbance after mTBI. METHODS: From May 2012 to Aug 2015, 189 mTBI patients completed baseline (1st week post-mTBI) and follow-up (6th week post-mTBI) sleep assessments that involved using the Pittsburgh Sleep Quality Index (PSQI). APOE genotypes were determined by sequencing the products of polymerase chain reaction from genomic DNA. Statistical analyses were performed using the Wilcox signed-rank or chi-square test. RESULTS: Thirty-five (18.5%) participants were APOE4 carriers. At baseline, the demographic data and the severity of sleep disturbance were similar in both groups. APOE4 carriers demonstrated significant improvement in the overall PSQI score (8.34±3.9 at baseline and 7.43±3.99 at follow-up, p = 0.05) and scores of several PSQI subscales, including sleep disturbance, sleep latency, daytime dysfunction caused by sleepiness, and overall sleep quality, which was similar to APOE4 noncarriers. CONCLUSION: APOE4 is not associated with the recovery of sleep disturbance after mTBI.

Evaluation of the teratogenic effects of three traditional Chinese medicines, Si Jun Zi Tang, Liu Jun Zi Tang and Shenling Baizhu San, during zebrafish pronephros development.

The aim of this study was to evaluate the teratogenic effects of three common Chinese medical prescriptions, Si Jun Zi Tang (SJZT), Liu Jun Zi Tang (LJZT) and Shenling Baizhu San (SLBS), during zebrafish pronephros development. We used the transgenic zebrafish line Tg(wt1b:EGFP) to assess the teratogenic effects using 12 different protocols, which comprised combinations of 4 doses (0, 25, 250, 1,250 ng/mL) and 3 exposure methods [methods I, 12-36 hours post fertilization (hpf), II, 24-48 hpf, and III, 24-36 hpf]. As a result, few defects in the kidneys were observed in the embryos exposed to 25 ng/mL of each medical prescription. The percentage of kidney malformation phenotypes increased as the exposure concentrations increased (25 ng/mL, 0-10%; 250 ng/mL, 0-60%; 1,250 ng/mL, 80-100%). Immunohistochemistry for α6F, which is a basolateral and renal tubular differentiation marker, revealed no obvious defective phenotypes in either SJZT- or LJZT-treated embryos, indicating that these Chinese medical prescriptions had minimal adverse effects on the pronephric duct. However, SLBS-treated embryos displayed a defective phenotype in the pronephric duct. According to these findings, we suggest (1) that the Chinese medical prescriptions induced kidney malformation phenotypes that are dose dependent and (2) that the embryonic zebrafish kidney was more sensitive to SLBS than SJZT and LJZT.

Atypical Ramsay Hunt syndrome.

Ramsay Hunt syndrome (RHS) is the reactivation of herpes zoster in the geniculate ganglion and typically presents the triad of ipsilateral peripheral type facial paralysis, ear pain, and erythematous vesicles in the external auditory canal and auricle. However, some unusual variants may occur. Here we present a patient of atypical RHS with uncommonly extensive dermatomal involvement of cranial nerve (CN) V2 and V3 and cervical roots, C2, C3 in addition to CN VII and VIII involvement.

A Case Report of Japanese Encephalitis Focusing on MR Findings.

meningitis or encephalitis with or without neurological deficits. JEV typically attacks the thalamus, corpus striatum, brainstem and spinal cord. The laboratory diagnosis of JEV infection involves the detection of anti-JEV antibody IgMs using an enzyme-linked immunosorbent assay (ELISA), which has high sensitivity and specificity. Because of the lack of a specific antiviral therapy, JE is usually managed by symptomatic treatment and supportive care. We report a case of JE in a 34-year-old man. With a clinical presentation similar to herpes simplex virus encephalitis, the patient was finally diagnosed as having JE. The distinction of different viral encephalitides in MR findings is briefly reviewed.

Efficacy of Vestibular Rehabilitation in Vestibular Neuritis: A Systematic Review and Meta-analysis.

OBJECTIVE: This study aimed to evaluate the efficacy of vestibular rehabilitation in vestibular neuritis. DESIGN: A randomized controlled trial was collected from MEDLINE, Embase, Cochrane Library, PEDro, LILACS, and Google Scholar before May 2023. RESULTS: This study included 12 randomized controlled trials involving 536 patients with vestibular neuritis. Vestibular rehabilitation was comparable with steroids in dizziness handicap inventory score at the first, sixth, and 12th months (pooled mean differences: -4.00, -0.21, and -0.31, respectively); caloric lateralization at the third, sixth, and 12th months (pooled mean difference: 1.10, 4.76, and -0.31, respectively); and abnormal numbers of vestibular-evoked myogenic potentials at the first, sixth, and 12th months. Patients receiving a combination of rehabilitation and steroid exhibited significant improvement in dizziness handicap inventory score at the first, third, and 12th months (mean difference: -14.86, pooled mean difference: -4.63, mean difference: -9.50, respectively); caloric lateralization at the first and third months (pooled mean difference: -10.28, pooled mean difference: -8.12, respectively); and numbers of vestibular-evoked myogenic potentials at the first and third months (risk ratios: 0.66 and 0.60, respectively) than did those receiving steroids alone. CONCLUSIONS: Vestibular rehabilitation is recommended for patients with vestibular neuritis. A combination of vestibular rehabilitation and steroids is more effective than steroids alone in the treatment of patients with vestibular neuritis.

YTHDF3 Modulates EGFR/ATK/ERK/p21 Signaling Axis to Promote Cancer Progression and Osimertinib Resistance of Glioblastoma Cells.

BACKGROUND/AIM: Despite recent advances in EGFR-tyrosine kinase inhibitor (TKI) drugs for glioblastoma multiforme (GBM), intrinsic EGFR alterations in GBM have resulted in drug resistance and unsatisfactory clinical development of EGFR-TKIs. Determining the unknown mechanisms underlying EGFR-TKI drug resistance is an urgent, but unmet, medical need for GBM. Although several m6A RNA methylation regulators, such as reader YTHDF1/2, were recently predicted to be related to GBM recurrence, none was associated with resistance to the 3rd generation EGFR-TKI osimertinib. MATERIALS AND METHODS: Osimertinib-resistant GBM cells (U87OSR) were established to ascertain the correlation between m6A expression and osimertinib resistance, prior to systemic analyses on m6A writers, erasers, and readers. YTHDF3-silencing was employed to reveal changes in IC50, cellular migration, cancer stemness, and p21-guided senescence in U87OSR cells. Signaling pathways and an in vivo xenograft model of U87OSR cells were investigated to delineate the influence of osimertinib-resistance and elevated YTHDF3 expression. RESULTS: YTHDF3 played a crucial role in inducing cellular proliferation, migration, and stemness in U87OSR GBM cells. Importantly, silencing of YTHDF3 markedly reduced the activation of certain signaling pathways, including EGFR- or ITGA7- AKT, and ERK in U87OSR cells. Our study also revealed the oncogenic function of YTHDF3 in inducing senescence escape via p21 down-regulation. In contrast, silencing of YTHDF3 resulted in increased p21 expression, senescence, and suppressed tumor growth in our osimertinib-resistant preclinical model. CONCLUSION: Overall, our research underscores the novel potential of YTHDF3 as a new pharmacological target in GBM treatment, specifically for patients with osimertinib-resistant or refractory tumors.

Heterogeneity of Alzheimer's disease identified by neuropsychological test profiling.

Alzheimer's disease (AD) is a highly heterogeneous disorder. Untangling this variability could lead to personalized treatments and improve participant recruitment for clinical trials. We investigated the cognitive subgroups by using a data-driven clustering technique in an AD cohort. People with mild-moderate probable AD from Taiwan was included. Neuropsychological test results from the Cognitive Abilities Screening Instrument were clustered using nonnegative matrix factorization. We identified two clusters in 112 patients with predominant deficits in memory (62.5%) and non-memory (37.5%) cognitive domains, respectively. The memory group performed worse in short-term memory and orientation and better in attention than the non-memory group. At baseline, patients in the memory group had worse global cognitive status and dementia severity. Linear mixed effect model did not reveal difference in disease trajectory within 3 years of follow-up between the two clusters. Our results provide insights into the cognitive heterogeneity in probable AD in an Asian population.

Development and Validation of Machine Learning Models to Classify Artery Stenosis for Automated Generating Ultrasound Report.

Duplex ultrasonography (DUS) is a safe, non-invasive, and affordable primary screening tool to identify the vascular risk factors of stroke. The overall process of DUS examination involves a series of complex processes, such as identifying blood vessels, capturing the images of blood vessels, measuring the velocity of blood flow, and then physicians, according to the above information, determining the severity of artery stenosis for generating final ultrasound reports. Generation of transcranial doppler (TCD) and extracranial carotid doppler (ECCD) ultrasound reports involves a lot of manual review processes, which is time-consuming and makes it easy to make errors. Accurate classification of the severity of artery stenosis can provide an early opportunity for decision-making regarding the treatment of artery stenosis. Therefore, machine learning models were developed and validated for classifying artery stenosis severity based on hemodynamic features. This study collected data from all available cases and controlled at one academic teaching hospital in Taiwan between 1 June 2020, and 30 June 2020, from a university teaching hospital and reviewed all patients' medical records. Supervised machine learning models were developed to classify the severity of artery stenosis. The receiver operating characteristic curve, accuracy, sensitivity, specificity, and positive and negative predictive value were used for model performance evaluation. The performance of the random forest model was better compared to the logistic regression model. For ECCD reports, the accuracy of the random forest model to predict stenosis in various sites was between 0.85 and 1. For TCD reports, the overall accuracy of the random forest model to predict stenosis in various sites was between 0.67 and 0.86. The findings of our study suggest that a machine learning-based model accurately classifies artery stenosis, which indicates that the model has enormous potential to facilitate screening for artery stenosis.

Vestibular paroxysmia: Long-term clinical outcome after treatment.

Objective: To study the long-term treatment outcome of vestibular paroxysmia (VP). Study design: Retrospective study. Setting: Tertiary referral hospital. Methods: We analyzed records of 29 consecutive patients who were diagnosed with VP and who were treated with VP-specific anticonvulsants for at least 3 months. Patients were followed for a minimum of 6 months. We recorded and assessed starting and target dosage of medications, time to achieve adequate therapeutic response, adverse effects, and the rates of short-term and long-term remission without medication. Results: All 29 patients were started on oxcarbazepine as first-line treatment, and 93.1% and 100% of patients reported good-to-excellent therapeutic response within 2 and 4 weeks, respectively. Three patients switched to other anticonvulsants at 3 months. At long-term follow-up (8-56 months), most (84.6%) oxcarbazepine-treated patients maintained good therapeutic response at doses between 300 and 600 mg/day. Eleven (37.9%) patients experienced complete remission without medication for more than 1 month, of which six (20.7%) had long-term remission off medication for more than 12 months. Nineteen (65.5%) patients had neurovascular compression (NVC) of vestibulocochlear nerve on MRI, but its presence or absence did not predict treatment response or remission. Conclusion: Low-dose oxcarbazepine monotherapy for VP is effective over the long term and is generally well-tolerated. About 20% of patients with VP in our study had long-term remission off medication.

Association between Statin Use and Risk of Parkinson's Disease: Evidence from 18 Observational Studies Comprising 3.7 Million Individuals.

The potential impact of statins on the risk of Parkinson's disease (PD) is still controversial; therefore, we conducted a comprehensive meta-analysis of observational studies to examine the effect of statin use on the risk of PD. We searched electronic databases, such as PubMed, EMBASE, Scopus, and Web of Science, for articles published between 1 January 2000 and 15 March 2022. Cohort studies which examined the association between statins and PD risk in the general population were also included. Two authors assessed the data and extracted all potential information for analysis. Random effects meta-analyses were performed to measure the risk ratio (RR) and 95% confidence intervals (CIs). Eighteen cohort studies including 3.7 million individuals with 31,153 PD participants were identified. In statin users, compared with non-users, the RR for PD was 0.79 (95% CI: 0.68-0.91). In a subgroup analysis of PD, this association was observed with medium and high quality, and the studies were adjusted for age, gender, and smoking status. When the data were stratified according to the duration of exposure, long-duration statin use was associated with a decreased risk of PD (RR = 0.49; 95% CI: 0.26-0.92). There was no significant decrease in the risk of PD in short-term statin users (RR = 0.94; 95% CI: 0.67-1.31). Moreover, no significant difference in the reduction in the risk of PD was observed between men (RR = 0.80; 95% CI: 0.75-0.86) and women (RR = 0.80; 95% CI: 0.75-0.86). Although our findings confirm a reduction in the PD risk associated with statin treatment and suggest that statins play a clinically favorable role, these findings should be interpreted with caution. Future randomized control trials with an ad hoc design are needed to confirm the potential utility of statins in reducing the risk of PD.