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Learning-based progression detection of Alzheimer's disease using 3D MRI images
No full text[[abstract]]Alzheimer's disease (AD) is an irreversible brain disease. In addition to the functional deterioration of memory and cognition, patients with severe conditions lose their self-care ability. Patients exhibiting symptoms are often attributed to aging and thus lack proper medical care. If it can be diagnosed early, the doctor can provide adequate treatments to mitigate the symptoms. Magnetic resonance imaging (MRI) can reflect the characteristics of different human tissues and organs, and is a common tool implemented in clinical examinations. In this study, we tested learning-based approaches to detect disease progression in AD patients using MRI. Specifically, each patient is categorized as one of the following four classes: cognitive normal, early mild cognitive impairment, late mild cognitive impairment, and AD. To extract 3D information in MRI, we proposed a 3D convolutional neural network structure based on ResNet3D-18. We designed various multiclass classification frameworks. Moreover, we implemented ensemble classification combining these frameworks. Experiments demonstrated great potential for learning-based approaches on the Alzheimer's Disease Neuroimaging Initiative dataset. The ensemble approach performed the best with an accuracy of 0.950, which is competitive with neurologists in diagnosing AD progression in clinical practice. With precise detection, patients can understand their conditions early and seek proper treatments
Polycyclic aromatic hydrocarbons ( Pahs) aggravate Hfd- induced nafld through increasing hepatocyte sphingosine-1phosphate
No full text[[abstract]]Background: Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide and exposure to environmental pollutants, including polycyclic aromatic hydrocarbons (PAHs), is suggested to be a risk factor for NAFLD; however, the regulatory mechanisms remain to be elucidated. Sphingolipid dysregulation has been linked to NAFLD development and we have previously demonstrated that exposure to PAH significantly induced oxidation of sphingosine-1-phosphate (S1P) lyase (SGPL1), resulting in reduced lyase activity and increased levels of S1P, a bioactive sphingolipid metabolite. Thus, we aimed to investigate the mechanistic impact of PAH, mostly derived from air pollution and processed food, on NAFLD progression and explored whether SGPL1 and S1P were critically involved. Methods: Wild-type (WT) and mutant Sgpl1C317A knock-in (C to A mutant at position 317 rendering resistance to oxidation) mice were fed with a high-fat diet (HFD, 60% fat calories) for 8 weeks to induce NAFLD, and indeno[1,2,3-cd]pyrene (IP) was administered by oral gavage every three days during this period to examine the effects of PAH on NAFLD progression. Mouse primary hepatocytes (MPHs) were also isolated using classic two-step collagenase perfusion method for in vitro study. Results: Reduced levels of weight gain, fatty liver, and serum S1P were observed in Sgpl1 KI mice compared to those of WT mice upon HFD and IP treatments. Increased lipid accumulation and upregulated S1P levels were found in WT MPH upon IP treatment, while inhibition of SGPL1 increased lipid accumulation and S1P levels in MPH derived from Sgpl1 KI mice. Also, pharmacological inhibition of SPHK1, but not SPHK2, decreased IP-induced S1P levels and lipid accumulation in MPH derived from WT mice, indicating that IP upregulated S1P through both SPHK1- and SGPL1-mediated pathways, which, in turn, increased intracellular lipid deposition in hepatocytes. Conclusion: PAH upregulated hepatocyte S1P by inducing SPHK1 activation and suppressing SGPL1 activity, thereby promoting HFD-induced NAFLD. Collectively, these results suggested the importance of SGPL1 in regulating S1P levels in NAFLD under the influence of environmental pollutants, such as PAHs
[[alternative]]屏東縣社區護理師高齡友善照護之經驗－以長者健康整合式評估與照護為例
No full text[[abstract]]Population aging has become a prevalent societal trend in the 21st century, giving rise to intricate challenges for healthcare systems. Taiwan is expected to become a "super-aging society" in 2025. In 2020, the Health Promotion Administration, referencing World Health Organization (WHO) guidelines on integrated care for older people (ICOPE), began promoting person-centered functional assessments for older adults to prevent and delay disability, reduce reliance on formal healthcare, and promote healthy aging, aging in place, and active aging. Pingtung County faces a healthcare gap between urban and rural areas. To address this, the county's executive team integrated community and healthcare systems into a single Age-Friendly Health Network to help older adults self-detect intrinsic functional decline problems at an early stage and receive early treatment. The implementation of this network is being done in the following four phases: preparation, action, implementation and revision, and promotion. As of August 2024, ICOPE intake in the county reached 11,873, representing a coverage rate of 7.42%. In addition to inadequate training opportunities for community healthcare professionals, rural communities are currently confronted with a dearth of referral mechanisms for post-ICOPE screening aftercare services for anomalous cases, representing a significant challenge that demands collaboration between industry, government, academia, and research. In light of the expanding older adult population, community nursing can be a formidable undertaking, necessitating the provision of ongoing nursing professional training and psychosocial support
Durvalumab, tremelimumab, and platinum chemotherapy in EGFR mutation–positive NSCLC: An open-label Phase 2 trial (ILLUMINATE)
No full text[[abstract]]Introduction: EGFR-mutant NSCLC is associated with low mutation burden and low levels of PD-L1 expression. We conducted a phase 2 trial to determine the efficacy of durvalumab, tremelimumab, and platinum-pemetrexed in EGFR-mutant NSCLC after progression with EGFR tyrosine kinase inhibitors (TKIs). Methods: Participants were treated with induction durvalumab, tremelimumab, and platinum-pemetrexed, followed by durvalumab-pemetrexed maintenance. Participants were divided into two cohorts: (1) EGFR exon 20 T790M negative (T790M−, progressing on either first-line osimertinib, or on a single line of first/second generation TKI), and (2) T790M positive (T790M+, progressing on greater than or equal to 1 lines of TKI, including osimertinib). The primary endpoint was the confirmed objective response rate (ORR) assessed by the investigators. Progression-free survival and safety were secondary outcomes. Results: One hundred participants from Australia and Taiwan were enrolled. Median follow-up was 26 months with 88% and 96% experiencing progression events for T790M− and T790M+, respectively. The ORR for T790M− was 31% (95% confidence interval: 20–45), including two complete responses. The ORR for T790M+ was 21% (95% confidence interval: 12–34). Median durations of response were 9.5 months and 6.3 months for T790M− and T790M+, respectively; median progression-free survival rates were 6.5 months and 4.9 months, respectively. For T790M−, ORR was 27% for 50% or higher PD-L1 (n = 22) and 0% for less than 50% PD-L1 (n = 10), respectively. For T790M+, ORR was 17% for 50% or higher PD-L1 (n = 24). The safety profile was consistent with previous reports. Conclusions: Durvalumab, tremelimumab, and platinum-pemetrexed had modest anti-tumor activity in EGFR-mutant NSCLC after progression on TKI. The T790M− cohort had higher ORR and a longer duration of response. Immune adverse events were not increased with tremelimumab. The clinical registration number of this trial is NCT03994393
[[alternative]]Fused bicyclic pyrimidine compounds as aurora kinase inhibitors
No full text[[abstract]]본 명세서에 나타낸 화학식 (I)의 융합 다환 화합물(fused multicyclic compounds)가 개시된다. 또한, 단백질 키나아제(예를 들어, 오로라 키나아제)의 활성을 억제하는 방법과 이들 화합물로 단백질 키나아제 매개 장애(예를 들어, 암)를 치료하는 방법이 개시된다
Benzimidazole compounds and use thereof for treating alzheimer's disease or huntington's disease
No full text[[abstract]]Benzimidazole compounds of formula (I), shown below, are disclosed. The compounds are potent human glutaminyl cyclase inhibitors. Also disclosed is a pharmaceutical composition containing one of these compounds and a pharmaceutical acceptable carrier, as well as a method of treating Alzheimer's disease or Huntington's disease by administering to a subject in need thereof an effective amount of such a compound
[[alternative]]Proline derivatives
No full text[[abstract]]Compounds useful for treating hepatitis C virus infection. The compounds are of formula (I): wherein A, B, C, D, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, m, n, p, q, r, t, u, and v are defined herein. Also disclosed is a method for treating hepatitis C virus infection with these compounds
[[alternative]]Proline derivatives
No full text[[abstract]]본 발명은 화학식 (Ⅰ)의 화합물에 관한 것이다. 또한, 본 발명은 이러한 화합물과 함께 C형 간염 바이러스 감염의 치료 방법에 관한 것이다
Pyrrolidine derivatives
No full text[[abstract]]PYRROLIDINE COMPOUNDS DESCRIBED HEREIN AND METHODS FOR USING THEM TO INHIBIT DIPEPTIDYL PEPTIDASE IV AND TREAT TYPE II DIABETE
Neuromedin U signaling promote pro-tumor microenvironment in lung cancer
No full text[[abstract]]By using the GWAS approach, we have previously identified several genetic variants located on 4q12 that were significantly associated with PFS of patients with lung adenocarcinoma (ADC) receiving first-line EGFR-TKI therapy. Intriguingly, we found those genetic variants were significantly associated with expression level of NMU , which is known to be upregulated in lung ADC and significantly associated with patients' worse poor survival. Here we found that knockdown of NMU expression remarkedly suppressed lung ADC cell proliferation in vitro and xenograft tumor growth in mice model, while forced expression of NMU had exactly the opposite effects. Also, based on xenograft model of lung ADC in mice, we further found that NMU not only can promote cancer cell growth via autocrine effect, but also can affect other cell types, e.g., fibroblast cells via paracrine effect, to foster a pro-tumor milieu by providing survival advantages to cancer cells. Our findings may lead to innovation of novel biomarkers for stratification of patients for precision medicine of lung cancer (LC) and invention of new therapeutic agents that may benefit LC patients by improving their survival and prognosis