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Genetic predictors of ketamine treatment efficacy in east asian patients with treatment-resistant depression: A polygenic score analysis
No full text[[abstract]]Background: Low-dose ketamine infusion has emerged as a therapeutic option for patients with treatment-resistant depression (TRD). Although it shows potential for alleviating symptoms in some TRD patients, methods for predicting which patients will respond to treatment are still lacking. Methods: In this study, we investigated the genetic contribution to ketamine treatment outcomes using polygenic scores (PGSs) for 108 traits. We utilized a sample of TRD patients treated with ketamine (N=97) from the Taipei Veterans General Hospital cohort (VGHTP). The patients were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS) prior to the initiation of infusions, at 40 minutes and 240 minutes post-treatment on Day 1, and subsequently on Days 2 and 3. We employed PRS-CS and PRS-CSx, a method recognized for its ability to leverage cross-ancestry genome-wide association study (GWAS) data, to improve PGS estimates. Results: Various analytical approaches, including single and multiple PGS predictors, consistently identified PGS predictors for Interleukin-12p70 and Alzheimer's disease as notable candidates. These PGS predictors exhibited significant associations with the percentage improvement in MADRS scores on Day 3 (Interleukin-12p70: association estima = 6.59, P-value = 0.006; Alzheimer's disease: association estimate = -4.73, P-value = 0.03). Notably, although previous studies have shown a positive association between obesity measures, such as body mass index, and ketamine treatment efficacy, our study found PGS predictors of body weight and hip circumference to be important factors when controlling for actual body weight as a covariate. This suggests a significant role for genetic contributions to body weight and related measurements in ketamine treatment efficacy, warranting further investigations. Proficient machine and deep learning algorithms achieved moderate performance, with an area under the receiver operating characteristic curve (AUC) of 0.704 for predicting responders versus non-responders, defined as MADRS ≥ 50% improvement. Discussion: Our study identifies key PGS predictors for ketamine treatment efficacy in TRD and highlights the potency of multi-PGS approaches in East Asian populations. These findings have substantial implications for optimizing ketamine treatment strategies in TRD
Trends of vertebral height loss in normal older population
No full text[[abstract]]Objective: To use an automatic vertebral compression fracture (VCF) detection method to investigate the percentage of vertebral height loss of normal aging population and to determine the differences in sex, age, and vertebrate level. Specific objectives included (1) the occurrence of the most severe VCFs in each sex, vertebral level and age group; (2) the distribution of the percentage of vertebral height loss by vertebral level, age, sex; and (3) the range of percentage of vertebral height loss by normal aging population. Methods: All non-contrast MDCT images of 856 participants (300 women) with an average age of 59.6 y (aged 50–95) were collected between 4 January 2021 and 31 March 2022. The MDCT images were reconstructed into 2.5 mm thick slices for automatic VCF analysis by SmartBone software. The subjects were divided into seven age groups, each of 5 y. We assessed differences in VCF between seven groups and two sexes using ANOVA and independent T tests. The normal range of the percentage of vertebral height loss with a combination of all vertebral levels during normal aging using the normal distribution estimation method (95%CI) and the interquartile range method (1.5 interquartile range). Results: The results showed that the most severe VCF usually occurred at T7, T11, and T12 in men. However, women generally had the most severe VCF from T5 to T8 between the ages of 50–60, and in the latter, the most severe VCF concentrated in T8. In addition, the increasing trends in vertebral height loss percentages by vertebral level and age group in men and women, and the progress in vertebral height loss in women, was similar to those in men. The percentage of vertebral height loss in the normal range of all age groups of both sexes exceeded 25%, where men and women losing 33% of vertebral height between 70–80 y of age. Conclusion: For the first time, our results show trends in reduction in vertebral height during normal aging in older Asians, thereby providing a reference database for clinical practice in the diagnosis and treatment of osteoporotic compression fractures
Injectable hierarchical bioactive hydrogels with fibroblast growth factor 21/edaravone/caffeic acid asynchronous delivery for treating Parkinson's disease
No full text[[abstract]]Parkinson's disease (PD) is one of the most common long-term neurodegenerative disorders, with multiple comorbid psychiatric and behavioral abnormalities. The combination of clinical drugs targeting different symptoms with smart hydrogels to achieve asynchronous releases is highly translational and challenging. Here, a hierarchical bioactive hydrogel (OACDP) is designed with asynchronous release based on PD pathology. The hydrogel with caffeic acid-grafted polymer main chain is crosslinked using a micellar nanocrosslinker, with sufficient modulus (approximate to 167 Pa), antioxidant activity (> 50%), injectability (30-gauge syringe needle), and shape-adaptability. Each of the three drugs (caffeic acid, fibroblast growth factor 21, and Edaravone) is separately engaged in different micro- or nanostructures of the hydrogel and released with asynchronous kinetics of first-order release, zero-order release, or matching Korsmeyer-Peppas model. The triple-loaded hydrogel is injected into the brains of PD rats, showing behavioral improvement. Histological analysis revealed that the triple-loaded OACDP hydrogels are effective in achieving immediate neuroprotection, i.e., reduction the loss of tyrosine hydroxylase in substantia nigra compacta and striatum (retained approximate to 10-fold versus control), decreasing oxidative stress, reducing astrocyte and microglia activation, and stimulating the AMPK/PGC-1 alpha axis to regulate the mitochondrial function, providing a multi-dimensional PD therapy. The asynchronous release of OACDP hydrogel provides a new conception for PD treatment and other neurodegenerative diseases
Atezolizumab, bevacizumab, pemetrexed and platinum for EGFR-mutant NSCLC patients after EGFR TKI failure: A phase II study with immune cell profile analysis
No full text[[abstract]]BACKGROUND: Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) remains a significant hurdle for patients with EGFR-mutated non-small cell lung cancer (NSCLC), particularly those lacking the EGFR(T790M). IMpower 150 study demonstrated promising efficacy for a combination of immune-chemotherapy and bevacizumab in patients with EGFR-mutated NSCLC. METHODS: This open-label, single-arm, phase II trial evaluated the efficacy and immune cell profile of the modified regimen combining atezolizumab, bevacizumab (7.5 mg/kg) and chemotherapy in patients with EGFR-mutated NSCLC following TKI failure. The primary endpoint was objective response rate (ORR). The re-biopsy tissue specimens and serial peripheral blood samples were collected to analyse the immune cell profile and tumour microenvironments. RRESULTS: 22 EGFR-mutant NSCLC patients participated in this study. The ORR was 42.9%, with a disease control rate (DCR) of 100%. Median progression-free survival (PFS) was 6.3 months. Patients with programmed death-ligand 1 (PD-L1) expression ≥1% exhibited significantly higher ORR (75 vs. 23.1%; p = .032) and longer PFS (14.0 vs. 6.1 months; p = .022) compared with those with PD-L1 expression < 1%. Grade ≥ 3 adverse events occurred in 40.9% of patients. Higher peritumour nature killer (NK) cell infiltration and lower peripheral helper T cell counts before treatment were associated with favourable ORR and longer PFS, respectively. After disease progression, the proportion of S100A9(+) myelod-derived suppressor cells (MDSCs) increased, while regulatory T cells decreased. CONCLUSION: This modified combination regimen may be a promising therapeutic option for EGFR-mutant NSCLC patients with TKI resistance, especially those with PD-L1-positive tumours. Furthermore, immune cell profiling may aid in identifying patients who may benefit from this approach. KEY POINTS: The combination regimen yielded promising efficacy in NSCLC patients after EGFR-TKI resistance, particularly those with PD-L1-positive tumours. Higher peritumour NK cell and lower peripheral helper T cell were associated with favourable ORR and longer PFS, respectively. After disease progression, the proportion of S100A9(+) MDSC increased, but Treg cells decreased
[[alternative]]Corrigendum to “Enhancing intrinsic TGF-β signaling via heparan sulfate glycosaminoglycan regulation to promote mesenchymal stem cell capabilities and chondrogenesis for cartilage repair” [Int. J. Biol. Macromol. 282 (2024) 137242] (International Journal
No full text[[abstract]]The authors regret that an error in Fig. 5E and find the updated version below:[Formula presented
[[alternative]]Corrigendum to “Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with biliary tract cancer”: [ESMO Open 9 (2024) 103647] (ESMO Open (2024) 9(8), (S2059702924014169), (10.1016/j.esmoop.2024.103647))
No full text[[abstract]]The authors report that in the original publication the ESMO-MCBS v1.1 scores for durvalumab-cisplatin-gemcitabine and pembrolizumab-cisplatin-gemcitabine are 4 and 1, respectively. The higher ESMO-MCBS v1.1 score for cisplatin-gemcitabine-durvalumab is due to the high 2-year OS gain observed with this regimen (14.2%). This was, however, based on only 9 patients (2.6% of the durvalumab-treated patients) who were still alive at that time. Thus, it should be noted that it does not currently provide evidence that durvalumab is vastly superior to pembrolizumab in combination with cisplatin-gemcitabine as both drugs incur similar clinical benefit with a HR OS of 0.75 and 0.83 and absolute median OS benefit of 1.6 and 1.8 months, respectively. Future updates to the ESMO-MCBS methodology will account for the proportion of study patients included in tail of the curve survival analyses, resulting in a lower MCBS score for durvalumab-cisplatin-gemcitabine. Recommendation 4a should read as follows: “Recommendation 4a. The combination of cisplatin-gemcitabine with durvalumab or pembrolizumab should be considered as standard of care in first-line BTC [I, A; ESMO-Magnitude of Clinical Benefit (MCBS) v1.1 score for durvalumab: 4; ESMO-MCBS v1.1 score for pembrolizumab: 1]. Cisplatin-gemcitabine-S1 is an alternative therapeutic option for fit patients [II, B].”[Figure presented] The revised Figure 1 Algorithm for the treatment of biliary tract cancer is given below. The authors would like to apologise for any inconvenience caused
CpG-oligodeoxynucleotide, immunogenic composition including the same, and method of inducing immune response by the same
No full text[[abstract]]A CpG-oligodeoxynucleotide (CpG-ODN) for inducing a TLR9 activated immune response, a TLR21 activated immune response or a combination thereof in a host is provided. The CpG-ODN includes one or more copies of the sequences of GTCGTT, one or more copies of the sequences of GTT and one or more copies of the sequences of TTTT, wherein at least one copy of the sequence of GTCGTT is encoded between the sequence of GTT and the sequence of TTTT. Further, an immunogenic composition including the CpG-ODN and a method of inducing immune response by the same are also provided
MAP4K3作为自体免疫疾病、癌症、发炎及IL‑17相关疾病的生物标记及治疗标的
No full text[[abstract]]本发明揭示用于鉴别治疗生发中心激酶类激酶GLK(也称为MAP4K3)介导的疾病的治疗剂的方法。揭示用于侦测以化合物调节GLK信号传导的方法。也揭示用于侦测自体免疫疾病及/或癌症的存在及/或严重程度的方法
Phage display selected chicken antibodies targeting surface alpha enolase in staphylococcus aureus
No full text[[abstract]]Staphylococcus aureus, a prevalent gram-positive bacterium in human populations, poses a significant risk for causing serious opportunistic infections and increasing antibiotic resistance. Alpha-enolase in S. aureus plays important roles in extracellular matrix binding and biofilm formation. These functions enable S. aureus to invade host tissues and cause infections. The aim of this study was to develop specific alpha-enolase chicken antibodies through phage display technology targeting S. aureus surface proteins as a potential alternative to antibiotic therapy. A chicken was immunized with recombinant S. aureus alpha-enolase, leading to the construction of two phage display single-chain variable fragment libraries of 3.32 x 10(6) and 8.60x10(5) transformants with different linker lengths. After four rounds of biopanning, five single-chain variable fragment antibody clones, including three with high binding affinities (SaS1, SaS2, and SaL2), were selected. These clones exhibited distinct binding patterns in epitope mapping and cross-reaction assays, with SaS1 and SaS2 specifically recognizing S. aureus alpha-enolase and SaL2 cross-reacting with Streptococcus pneumoniae alpha-enolase. Furthermore, the specificity of these antibody clones toward clinical S. aureus strains, including methicillin-sensitive and methicillin-resistant strains, was validated through cell-based enzyme-linked immunosorbent assays (ELISA) and flow cytometry assays. The identification of SaS1, SaS2, and SaL2 underscores their diagnostic and therapeutic potential, offering promising alternatives to traditional antibiotic therapies
Association between wet-bulb globe temperature with peptic ulcer disease in different geographic regions in a large Taiwanese population study
No full text[[abstract]]Background Peptic ulcer disease (PUD) is a common and important cause of morbidity worldwide, with a large impact on healthcare costs. Little research has been conducted on the association between wet-bulb globe temperature (WBGT) and PUD. The aim of this study was to explore this association among different geographical regions of Taiwan in a large sample of participants. Methods This is a cross-sectional study. The study participants (n = 120,424) were enrolled from the Taiwan Biobank (TWB) and resided across northern, central, southern and eastern Taiwan. Self-reported questionnaires were used to ascertain the occurrence of PUD. Average WBGT values were recorded during working hours (8:00 AM to 5:00 PM) and the noon period (11:00 AM to 2:00 PM) for each participant at 1, 3, and 5 years before the TWB survey year. The association between WBGT and PUD was examined with logistic regression analysis. Results The 1-year and 5-year noon WBGT values per 1 degrees C increase were significantly associated with a low prevalence of PUD in northern Taiwan (odds ratio [OR], 0.960, 95% confidence interval [CI], 0.925-0.955; OR, 0.962, 95% CI, 0.929-0.997; respectively). In contrast, there were no significant associations between WBGT and PUD in central Taiwan. In southern Taiwan, the 1-, 3-, and 5-year WBGT values per 1 degrees C increase during the noon period (OR, 0.875, 95% CI, 0.873-0.909; OR, 0.860, 95% CI, 0.825-0.896; OR, 0.848, 95% CI, 0.812-0.885; respectively) and working period (OR, 0.852, 95% CI, 0.825-0.880; OR, 0.845, 95% CI, 0.816-0.876; OR, 0.832, 95% CI, 0.0.801-0.863; respectively) were significantly associated with a low prevalence of PUD. However, in eastern Taiwan, the 1-, 3-, and 5-year WBGT values per 1 degrees C increase during the noon period (OR, 1.074, 95% CI, 1.022-1.127; OR, 1.058, 95% CI, 1.013-1.104; OR, 1.058, 95% CI, 1.013-1.105; respectively), and the 3- and 5-year WBGT values per 1 degrees C increase during the working period were significantly associated with a high prevalence of PUD (OR, 1.049, 95% CI, 1.003-1.097; OR, 1.047, 95% CI, 1.001-1.095; respectively). Based on nonlinear trend analysis, WBGT was categorized into three groups for the noon period or work period, and the results were similar to and generally consistent with those in linear models. Conclusion The associations between WBGT and PUD differed across the geographical regions of Taiwan. In northern and southern Taiwan, increases in average WBGT values were significantly associated with a low prevalence of PUD. In addition, this relationship was much stronger in southern Taiwan than in northern Taiwan. Of note, there was a reverse relationship between WBGT and PUD during the noon and working periods in eastern Taiwan. Further studies are needed to elucidate the effects of WBGT on PUD