A Transfer Learning Method for Detecting Alzheimer's Disease Based on Speech and Natural Language Processing.

Alzheimer's disease (AD) is a neurodegenerative disease that is difficult to be detected using convenient and reliable methods. The language change in patients with AD is an important signal of their cognitive status, which potentially helps in early diagnosis. In this study, we developed a transfer learning model based on speech and natural language processing (NLP) technology for the early diagnosis of AD. The lack of large datasets limits the use of complex neural network models without feature engineering, while transfer learning can effectively solve this problem. The transfer learning model is firstly pre-trained on large text datasets to get the pre-trained language model, and then, based on such a model, an AD classification model is performed on small training sets. Concretely, a distilled bidirectional encoder representation (distilBert) embedding, combined with a logistic regression classifier, is used to distinguish AD from normal controls. The model experiment was evaluated on Alzheimer's dementia recognition through spontaneous speech datasets in 2020, including the balanced 78 healthy controls (HC) and 78 patients with AD. The accuracy of the proposed model is 0.88, which is almost equivalent to the champion score in the challenge and a considerable improvement over the baseline of 75% established by organizers of the challenge. As a result, the transfer learning method in this study improves AD prediction, which does not only reduces the need for feature engineering but also addresses the lack of sufficiently large datasets.

Berbamine Suppresses the Growth of Gastric Cancer Cells by Inactivating the BRD4/c-MYC Signaling Pathway.

PURPOSE: Berbamine (Ber), a bioactive constituent extracted from a traditional Chinese medicinal herb, has been shown to exhibit broad inhibitory activity on a panel of cancer cell types. However, its effects and the underlying molecular mechanisms on gastric cancer (GC) remain poorly understood. METHODS: The anti-growth activity of Ber on two GC cell lines and normal gastric epithelial cell line were evaluated using MTS and clone formation assay. Flow cytometry analysis was employed to evaluate the cell cycle distribution and apoptosis of GC cells. Western blot and quantitative PCR (qPCR) analysis were employed to investigate the anti-GC mechanism of Ber. The inhibitory activity and binding affinity of Ber against BRD4 were evaluated by homogeneous time-resolved fluorescence (HTRF) and surface plasmon resonance (SPR) assay, respectively. Molecular docking and molecular simulations were conducted to predict the interaction mode between BRD4 and Ber. RESULTS: The results demonstrated that Ber reduced the proliferation of GC cell lines SGC-7901 and BGC-823 and induced cell cycle arrest and apoptosis. Mechanistically, Ber was identified as a novel natural-derived BRD4 inhibitor through multiple experimental assay, and its anti-GC activity was probably mediated by BRD4 inhibition. Molecular modeling studies suggested that Ber might bind to BRD4 primarily through hydrophobic interactions. CONCLUSION: Our study uncovered the underlying anti-GC activity of Ber in vitro and suggested that Ber holds promise as a potential lead compound in the discovery of novel BRD4 inhibitors.

Phillygenin, a MELK Inhibitor, Inhibits Cell Survival and Epithelial-Mesenchymal Transition in Pancreatic Cancer Cells.

INTRODUCTION: Pancreatic cancer (PC) is one of the leading causes of cancer, with the lowest 5-year survival rate of all cancer types. Given the fast metastasis of PC and its resistance to surgery, radiotherapy, chemotherapy, and combinations thereof, it is imperative to develop more effective anti-PC drugs. Phillygenin (PHI) has been reported to exert anti-cancer, anti-bacterial, and anti-inflammatory properties. However, the mechanism of PHI in the development of PC is still unclear. METHODS: The cytotoxicity of PHI in pancreatic cancer cells was evaluated by MTT assay, and clonogenic assay was used to test the anti-proliferation of PHI. The pro-apoptotic effect of PHI was detected by flow cytometry analysis. The changes of epithelial-mesenchymal transition (EMT) in pancreatic cancer cells treated with PHI were determined by Western blot. Transwell assay was used to test the migration and invasion of PC cells after treatment with PHI. Molecular docking was used to predict the potential binding site of candidate target with PHI. RESULTS: PHI could inhibit the proliferation, migration, and EMT of PC cells (PANC-1 and SW1990) and induce its apoptosis. Analysis of the Cancer Genome Atlas database indicated that elevated MELK levels correlated with poor overall survival (OS) and disease-free survival (DFS) of PC patients. In addition, molecular modeling showed that PHI may potentially target the catalytic domain of maternal embryonic leucine zipper kinase (MELK). Overexpression of MELK muted the anti-PC effects of PHI. CONCLUSION: PHI holds promise as a potent candidate drug for the treatment of PC via targeted MELK.

Extrapyramidal side effect of donepezil hydrochloride in an elderly patient: A case report.

INTRODUCTION: Alzheimer disease (AD) is a neurodegenerative disease characterized by progressive cognitive dysfunction, which is mainly manifested as memory impairment and a reduced ability to self-care, often accompanied by neuropsychiatric and behavioral disorders. Donepezil is the second drug to be approved by the US FDA for the treatment of AD. Of the five FDA-approved drugs for AD treatment, donepezil is currently the most widely used. Here, we report an extrapyramidal adverse reaction to donepezil in an elderly patient with AD. PATIENT CONCERNS: An 87-year-old woman presented with a 1-year history of forgetfulness that was aggravated since the past 2 months. She had a long-term history of multiple major conditions, including hypertension, diabetes, osteoporosis, and arterial plaques. Brain imaging showed age-related changes, and her Mini Mental State Examination score was 20. Other tests revealed no abnormalities apart from multiple thyroid nodules on ultrasonography. DIAGNOSIS: She was diagnosed with AD, hypertension, type 2 diabetes mellitus, diabetic neuropathy, osteoporosis, carotid and lower-extremity arterial plaques, thyroid nodules. INTERVENTIONS: She was treated with donepezil (5 mg/day), amlodipine besylate (5 mg/day), glimepiride (4 mg/day), methylcobalamin (1.5 mg/day), calcium carbonate D3 (600 mg/day), simvastatin (20 mg/day) and enteric-coated aspirin (100 mg/day). OUTCOMES: Four days later, she experienced fatigue, panic, sweating, and one episode of vomiting. On the 5th day, she developed increased muscle tension, speech difficulty, and involuntary tremors. Imaging and blood tests revealed no obvious abnormality, and the patient was not receiving psychotropic drugs. An extrapyramidal adverse reaction to donepezil was considered, and the drug was discontinued, after which the symptoms gradually disappeared. CONCLUSION: Serious adverse reactions to donepezil can occur in elderly patients, who typically require multiple medications for a variety of comorbidities. In particular, extrapyramidal reactions have occurred when donepezil is administered in combination with psychotropic drugs. However, in our patient, an extrapyramidal adverse reaction occurred in the absence of psychotropic drugs. Thus, clinicians must be aware of inter-individual differences in drug actions and possible serious adverse reactions, and carefully monitor these patients to ensure the timely detection of adverse events and their safe treatment.

Association of obesity with chronic kidney disease in elderly patients with nonalcoholic fatty liver disease.

BACKGROUND/AIMS: This study investigated an association between obesity and impaired renal functions in elderly patients with nonalcoholic fatty liver disease (NAFLD) and evaluated the risk factors for chronic kidney disease (CKD) in these patients. MATERIALS AND METHODS: A cross-sectional study was performed involving 515 elderly patients (≥ 60 years old) with NAFLD. Demographics, body mass index (BMI), medical history, and laboratory parameters were compared for groups stratified by obesity (≥ 28 kg/m2) or CKD. An association between obesity and CKD was analyzed, and a multivariate logistic regression analysis was conducted for risk factors associated with CKD. RESULTS: In the overall population, 28.7% were obese and 54.8% had CKD; there were more women (58.8%) than men. The prevalence of hypertension and diabetes was similar between the obese and nonobese groups and between the CKD and non-CKD groups. Obese patients had significantly higher levels of serum uric acid and estimated glomerular filtration rates when compared with the nonobese group. When compared with those without CKD, patients with CKD were significantly older in addition to having higher BMI and serum uric acid levels. The multivariate logistic regression analysis indicated that CKD was positively associated with age, BMI, and serum uric acid levels. CONCLUSION: Elderly obese patients with NAFLD are at a higher risk of CKD. NAFLD patients with advanced age, greater BMI, or higher serum uric acid levels are more prone to developing CKD. The renal function of NAFLD patients should be closely monitored.