Gene set correlation enrichment analysis for interpreting and annotating gene expression profiles.

Pathway analysis, including nontopology-based (non-TB) and topology-based (TB) methods, is widely used to interpret the biological phenomena underlying differences in expression data between two phenotypes. By considering dependencies and interactions between genes, TB methods usually perform better than non-TB methods in identifying pathways that include closely relevant or directly causative genes for a given phenotype. However, most TB methods may be limited by incomplete pathway data used as the reference network or by difficulties in selecting appropriate reference networks for different research topics. Here, we propose a gene set correlation enrichment analysis method, Gscore, based on an expression dataset-derived coexpression network to examine whether a differentially expressed gene (DEG) list (or each of its DEGs) is associated with a known gene set. Gscore is better able to identify target pathways in 89 human disease expression datasets than eight other state-of-the-art methods and offers insight into how disease-wide and pathway-wide associations reflect clinical outcomes. When applied to RNA-seq data from COVID-19-related cells and patient samples, Gscore provided a means for studying how DEGs are implicated in COVID-19-related pathways. In summary, Gscore offers a powerful analytical approach for annotating individual DEGs, DEG lists, and genome-wide expression profiles based on existing biological knowledge.

Comparing Low- or Standard-Dose Alteplase in Endovascular Thrombectomy: Insights From a Nationwide Registry.

BACKGROUND: Timely intravenous thrombolysis and endovascular thrombectomy are the standard reperfusion treatments for large vessel occlusion stroke. Currently, it is unknown whether a low-dose thrombolytic agent (0.6 mg/kg alteplase) can offer similar efficacy to the standard dose (0.9 mg/kg alteplase). METHODS: We enrolled consecutive patients in the multicenter Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke who had received combined thrombolysis (within 4.5 hours of onset) and thrombectomy treatment from January 2019 to April 2023. The choice of low- or standard-dose alteplase was based on the physician's discretion. The outcomes included successful reperfusion (modified Thrombolysis in Cerebral Infarction score, 2b-3), symptomatic intracerebral hemorrhage, 90-day modified Rankin Scale score, and 90-day mortality. The outcomes between the 2 groups were compared using multivariable logistic regression and inverse probability of treatment weighting-adjusted analysis. RESULTS: Among the 2242 patients in the Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke, 734 (33%) received intravenous alteplase. Patients in the low-dose group (n=360) were older, had more women, more atrial fibrillation, and longer onset-to-needle time compared with the standard-dose group (n=374). In comparison to low-dose alteplase, standard-dose alteplase was associated with a lower rate of successful reperfusion (81% versus 87%; adjusted odds ratio, 0.63 [95% CI, 0.40-0.98]), a numerically higher incidence of symptomatic intracerebral hemorrhage (6.7% versus 3.9%; adjusted odds ratio, 1.81 [95% CI, 0.88-3.69]), but better 90-day modified Rankin Scale score (functional independence [modified Rankin Scale score, 0-2], 47% versus 31%; adjusted odds ratio, 1.91 [95% CI, 1.28-2.86]), and a numerically lower mortality rate (9% versus 15%; adjusted odds ratio, 0.73 [95% CI, 0.43-1.25]) after adjusting for covariates. Similar results were observed in the inverse probability of treatment weighting-adjusted models. The results were consistent across predefined subgroups and age strata. CONCLUSIONS: Despite the lower rate of successful reperfusion and higher risk of symptomatic intracerebral hemorrhage with standard-dose alteplase, standard-dose alteplase was associated with a better functional outcome in patients receiving combined thrombolysis and thrombectomy.

Cross-site validation of lung cancer diagnosis by electronic nose with deep learning: a multicenter prospective study.

BACKGROUND: Although electronic nose (eNose) has been intensively investigated for diagnosing lung cancer, cross-site validation remains a major obstacle to be overcome and no studies have yet been performed. METHODS: Patients with lung cancer, as well as healthy control and diseased control groups, were prospectively recruited from two referral centers between 2019 and 2022. Deep learning models for detecting lung cancer with eNose breathprint were developed using training cohort from one site and then tested on cohort from the other site. Semi-Supervised Domain-Generalized (Semi-DG) Augmentation (SDA) and Noise-Shift Augmentation (NSA) methods with or without fine-tuning was applied to improve performance. RESULTS: In this study, 231 participants were enrolled, comprising a training/validation cohort of 168 individuals (90 with lung cancer, 16 healthy controls, and 62 diseased controls) and a test cohort of 63 individuals (28 with lung cancer, 10 healthy controls, and 25 diseased controls). The model has satisfactory results in the validation cohort from the same hospital while directly applying the trained model to the test cohort yielded suboptimal results (AUC, 0.61, 95% CI: 0.47─0.76). The performance improved after applying data augmentation methods in the training cohort (SDA, AUC: 0.89 [0.81─0.97]; NSA, AUC:0.90 [0.89─1.00]). Additionally, after applying fine-tuning methods, the performance further improved (SDA plus fine-tuning, AUC:0.95 [0.89─1.00]; NSA plus fine-tuning, AUC:0.95 [0.90─1.00]). CONCLUSION: Our study revealed that deep learning models developed for eNose breathprint can achieve cross-site validation with data augmentation and fine-tuning. Accordingly, eNose breathprints emerge as a convenient, non-invasive, and potentially generalizable solution for lung cancer detection. CLINICAL TRIAL REGISTRATION: This study is not a clinical trial and was therefore not registered.

Characteristic of school injuries in Asia: a cross-national, multi-center observational study.

BACKGROUND: To prevent school injuries, thorough epidemiological data is an essential foundation. We aimed to investigate the characteristics of school injuries in Asia and explore risk factors for major trauma. METHODS: This retrospective study was conducted in the participating centers of the Pan-Asian Trauma Outcome Study from October 2015 to December 2020. Subjects who reported "school" as the site of injury were included. Major trauma was defined as an Injury Severity Score (ISS) value of ≥16. RESULTS: In total, 1305 injury cases (1.0% of 127,715 events) occurred at schools. Among these, 68.2% were children. Unintentional injuries were the leading cause and intentional injuries comprised 7.5% of the cohort. Major trauma accounted for 7.1% of those with documented ISS values. Multivariable regression revealed associations between major trauma and factors, including age, intention of injury (self-harm), type of injury (traffic injuries, falls), and body part injured (head, thorax, and abdomen). Twenty-two (1.7%) died, with six deaths related to self-harm. Females represented 28.4% of injuries but accounted for 40.9% of all deaths. CONCLUSIONS: In Asia, injuries at schools affect a significant number of children. Although the incidence of injuries was higher in males, self-inflicted injuries and mortality cases were relatively higher in females. IMPACT: Epidemiological data and risk factors for major trauma resulting from school injuries in Asia are lacking. This study identified significant risk factors for major trauma occurring at schools, including age, intention of injury (self-harm), injury type (traffic injuries, falls), and body part injured (head, thoracic, and abdominal injuries). Although the incidence of injuries was higher in males, the incidence of self-harm injuries and mortality rates were higher in females. The results of this would make a significant contribution to the development of prevention strategies and relative policies concerning school injuries.

Assessment of the impact of resting heart rate on the risk of major adverse cardiovascular events after ischemic stroke: a retrospective observational study.

BACKGROUND: Although elevated heart rate is a risk factor for cardiovascular morbidity and mortality in healthy people, the association between resting heart rate and major cardiovascular risk in patients after acute ischemic stroke remains debated. This study evaluated the association between heart rate and major adverse cardiovascular events after ischemic stroke. METHODS: We conducted a retrospective cohort study analyzing data from the Chang Gung Research Database for 21,655 patients with recent ischemic stroke enrolled between January 1, 2010, and September 30, 2018. Initial in-hospital heart rates were averaged and categorized into 10-beats per minute (bpm) increments. The primary outcome was the composite of hospitalization for recurrent ischemic stroke, myocardial infarction, or all-cause mortality. Secondary outcomes were hospitalization for recurrent ischemic stroke, myocardial infarction, and heart failure. Hazard ratios and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, using the heart rate < 60 bpm subgroup as the reference. RESULTS: After a median follow-up of 3.2 years, the adjusted hazard ratios for the primary outcome were 1.13 (95% CI: 1.01 to 1.26) for heart rate 60-69 bpm, 1.35 (95% CI: 1.22 to 1.50) for heart rate 70-79 bpm, 1.64 (95% CI: 1.47 to 1.83) for heart rate 80-89 bpm, and 2.08 (95% CI: 1.85 to 2.34) for heart rate ≥ 90 bpm compared with the reference group. Heart rate ≥ 70 bpm was associated with increased risk of all secondary outcomes compared with the reference group except heart failure.  CONCLUSIONS: Heart rate is a simple measurement with important prognostic implications. In patients with ischemic stroke, initial in-hospital heart rate was associated with major adverse cardiovascular events.

Establishment of a cobia (Rachycentron canadum) gill cell line: A valuable tool for immune response studies.

Cobia (Rachycentron canadum), a commercially important marine fish, has been used to develop a novel gill cell line, designated CG, for the first time. The CG cell line was cultured in Leibovitz's-15 medium with 5% fetal bovine serum (FBS) and successfully sub-cultured more than 110 passages. It underwent verification through sequencing of the mitochondrial cytochrome C oxidase subunit I (COI) gene. Optimal growth rate was achieved when the CG cell line was cultured in a medium supplemented with 5% FBS, 1% Penicillin-Streptomycin (P/S), and 5 parts per thousand (ppt) of coral sea salt water, maintained at a temperature of 27 °C. The addition of 5 ppt of salt in the growth medium suggests that this cell line could be a viable in vitro tool for marine ecosystem toxicological studies or for culturing marine parasitic microorganisms. The CG cell line was also successfully transfected using the pTurbo-GFP plasmids, showing an 18% efficiency, with observable GFP expression. Furthermore, the cell line has been effectively cryopreserved. Gene expression analysis indicated that the CG cell line exhibits responsive regulation of immune gene expression when exposured to various stimulants, highlighting its potential as an in vitro platform for immune response studies. This makes it suitable for exploring dynamic immune signaling pathways and host-pathogen interactions, thereby offering valuable insights for therapeutic development.

Brain imaging prior to thrombectomy in the late window of large vessel occlusion ischemic stroke: a systematic review and meta-analysis.

PURPOSE: Optimal imaging modalities to select patients for endovascular thrombectomy (EVT) in the late window of acute ischemic stroke due to large vessel occlusions (AIS-LVO) are not known. We conducted a systematic review comparing outcomes of patients selected by non-contrast computed tomography (NCCT)/CT angiography (CTA) vs. those selected by CT perfusion (CTP) or magnetic resonance imaging (MRI) for EVT in these patients. METHODS: We searched PUBMED, EMBASE, and the Cochrane Library from January 1, 2000, to July 15, 2023, to identify studies comparing outcomes of patients selected for EVT by NCCT/CTA vs. CTP or MRI in the late time window for AIS-LVO. Primary outcome was independence (mRS 0-2) at 90 days or discharge. Secondary outcomes were symptomatic intracranial hemorrhage (sICH) and mortality. We pooled data across studies based on an inverse variance method. RESULTS: Six cohort studies with 4208 patients were included. Pooled results showed no significant difference in the rate of independence at 90 days or discharge (RR 0.96, 95% CI 0.88-1.03) and sICH (RR 1.26, 0.85-1.86) between patients selected by NCCT/CTA vs. CTP or MRI for EVT in the late window of AIS-LVO. However, patients selected by NCCT/CTA vs. CTP or MRI for EVT were associated with a higher risk of mortality (RR 1.21, 1.06-1.39). CONCLUSION: For AIS-LVO in the late window, patients selected by NCCT/CTA compared with those selected by CTP or MRI for EVT might have a comparable rate of functional independence and sICH. Baseline NCCT/CTA may triage AIS-LVO in the late window.

Associations of fish oil with cardiovascular disease events: results from the Taiwan longitudinal study in aging.

BACKGROUND: The effectiveness of fish oil in preventing cardiovascular events is still debating. Some studies indicate a correlation between the use of fish oil supplements and reduced mortality or decreased incidence of stroke. However, other studies show no significant association between fish oil intake and stroke prevention, indicating an ongoing debate. This study aimed at exploring which subjects may benefit more from fish oil supplementation. METHODS: This study utilized the data obtained through face-to-face interview from the Taiwan Longitudinal Study in Aging (TLSA). A total of 3,652 participants were included from the 2003 baseline data, after excluding patients with pre-existing ischemic heart disease or stroke. Participants were divided into two groups based on whether taking fish oil supplement or not. Participants were followed until 2015, estimating and comparing the all-cause mortality and cumulative incidence rate of stroke between both groups. RESULTS: The results of the 12-year longitudinal study showed that the cumulative incidence rate of stroke in the fish oil supplementation group was 5.7%, compared to 7.7% in the non-supplemented group (P < 0.05). Additionally, the crude hazard ratio for stroke was significantly lower in the fish oil supplementation group (HR = 0.686;95% CI 0.476-0.987). However, after adjusting potential confounders, the adjusted risk of stroke was lower only for the diabetic patients supplemented with fish oil (aHR = 0.123; 95% CI 0.016-0.930) compared to non-diabetic patients (aHR = 0.917; 95% CI 0.616-1.364). CONCLUSION: This study suggests that there is an association between fish oil supplementation and a lower cumulative incidence rate of subsequent stroke among diabetic patients.

Risk of serious infection and infection mortality in patients with psoriasis: A nationwide cohort study using the Taiwan National Health Insurance claims database.

BACKGROUND: The risks of serious infections that lead to hospitalization and mortality in patients with psoriasis in Asia have not been comprehensively studied. OBJECTIVES: We examined the incidence of serious infection and infection mortality in patients with psoriasis. METHODS: This population-based retrospective cohort study used the Taiwan National Health Insurance claims database from 2000 to 2017. Adult patients with psoriasis were identified by a relevant International Classification of Diseases (ICD) code and matched to six comparators without psoriasis on age and sex. Psoriasis patients were categorized as having moderate-to-severe disease once exposed to systemic therapies, phototherapy or biologic therapies. The incidence of serious infection and infection mortality were identified by ICD codes from inpatient hospitalization and death registration. Cox proportional hazard models were used to compare the risk, and the results were adjusted for covariates and presented as adjusted hazard ratios (aHR) and 95% confidence interval (95% CI). RESULTS: Overall, 185,434 psoriasis patients and 1,112,581 comparators were included. A higher rate of serious infection (aHR: 1.21, 95% CI: 1.19-1.22) was found in patients with psoriasis compared to matched comparators without psoriasis, and the risk was enhanced when patients had moderate-to-severe psoriasis (aHR: 1.30, 95% CI: 1.27-1.34). Specifically, there was an increased risk of serious infection due to respiratory infections (aHR: 1.11, 95% CI: 1.09-1.13), skin/soft-tissue infections (aHR: 1.57, 95% CI: 1.52-1.62), sepsis (aHR: 1.23, 95% CI: 1.19-1.27), urinary tract infections (aHR: 1.11, 95% CI: 1.08-1.14), hepatitis B (aHR: 1.18, 95% CI: 1.06-1.30) and hepatitis C (aHR: 1.49, 95% CI: 1.32-1.69). Furthermore, psoriasis patients were associated with a higher risk of infection-related mortality (aHR: 1.15, 95% CI: 1.11-1.18) compared to matched comparators. CONCLUSION: Patients with psoriasis had a higher risk of serious infection and infection mortality, which was enhanced by moderate-to-severe psoriasis. Practitioners should be aware of the increased risk in patients with psoriasis, but it should not be a barrier to offering effective treatment.

Discovery of N,N'-diarylurea molecules with activity against multidrug-resistant Staphylococcus aureus.

The emergence and global spread of methicillin-resistant Staphylococcus aureus (MRSA) pose a serious threat to public health, underscoring the urgent need for novel antibacterial interventions. Here, we screened 18 newly synthesized N,N'-diarylurea derivatives to identify compounds with activity against MRSA. Our investigations led to the discovery of a small molecule, SCB-24, which exhibited promising antimicrobial activity against MRSA USA300. Notably, SCB-24 demonstrated high activity even in the presence of 10% fetal bovine serum and showed excellent selectivity for bacterial over mammalian cells. SCB-24 also showed potent activity against various MRSA strains, including those resistant to second- and third-line antibiotics. Importantly, the efficacy of SCB-24 was inferior to that of vancomycin in MRSA-infected Galleria mellonella larvae. Overall, our findings suggest that SCB-24 has great potential as a new therapeutic for multidrug-resistant S. aureus infections.

Multipathway regulation induced by 4-(phenylsulfonyl)morpholine derivatives against triple-negative breast cancer.

Phenotypic drug discovery (PDD) is an effective drug discovery approach by observation of therapeutic effects on disease phenotypes, especially in complex disease systems. Triple-negative breast cancer (TNBC) is composed of several complex disease features, including high tumor heterogeneity, high invasive and metastatic potential, and a lack of effective therapeutic targets. Therefore, identifying effective and novel agents through PDD is a current trend in TNBC drug development. In this study, 23 novel small molecules were synthesized using 4-(phenylsulfonyl)morpholine as a pharmacophore. Among these derivatives, GL24 (4m) exhibited the lowest half-maximal inhibitory concentration value (0.90 µM) in MDA-MB-231 cells. To investigate the tumor-suppressive mechanisms of GL24, transcriptomic analyses were used to detect the perturbation for gene expression upon GL24 treatment. Followed by gene ontology (GO) analysis, gene set enrichment analysis (GSEA), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, multiple ER stress-dependent tumor suppressive signals were identified, such as unfolded protein response (UPR), p53 pathway, G2/M checkpoint, and E2F targets. Most of the identified pathways triggered by GL24 eventually led to cell-cycle arrest and then to apoptosis. In summary, we developed a novel 4-(phenylsulfonyl)morpholine derivative GL24 with a strong potential for inhibiting TNBC cell growth through ER stress-dependent tumor suppressive signals.

Blood pressure targets, medication consideration and unique concerns in elderly hypertension IV: Focus on frailty, orthostatic hypotension, and resistant hypertension.

Hypertension increases the risk of cardiovascular disease in the elderly. Although treating hypertension can reduce the risk of cardiovascular disease and its related mortality, it is also challenging because these patients could have frailty, orthostatic hypotension (OH) and resistant hypertension (RHTN), which makes them more susceptible to treatment-related adverse events. Identifying such patients and tailoring the choice of drugs and blood pressure targets is crucial to balance the harms and benefits. The Clinical Frailty Scale is recommended to assess elderly patients with hypertension and frailty. For very frail patients, unnecessary medications should be deprescribed to avoid adverse events. Hypertension and OH frequently co-occur in the elderly, and recognizing and managing OH is essential to prevent falls and adverse events. The management of blood pressure in elderly patients with frailty, OH, and RHTN is complex, requiring the patients, their family and caregivers to be involved in decision-making to ensure that treatment plans are well-informed and aligned with the patient's needs.

Detection of Interleukin-1 ß (IL-1ß) in Single Human Blastocyst-Conditioned Medium Using Ultrasensitive Bead-Based Digital Microfluidic Chip and Its Relationship with Embryonic Implantation Potential.

The implantation of human embryos is a complex process involving various cytokines and receptors expressed by both endometrium and embryos. However, the role of cytokines produced by a single embryo in successful implantation is largely unknown. This study aimed to investigate the role of IL-1ß expressed in a single-embryo-conditioned medium (ECM) in embryo implantation. Seventy samples of single ECM were analyzed by a specially designed magnetic-beads-based microfluidic chip from 15 women. We discovered that IL-1ß level increased as the embryo developed, and the difference was significant. In addition, receiver operator characteristic (ROC) curves analysis showed a higher chance of pregnancy when the IL-1ß level on day 5 ECM was below 79.37 pg/mL and the difference between day 5 and day 3 was below 24.90 pg/mL. Our study discovered a possible association between embryonic proteomic expression and successful implantation, which might facilitate single-embryo transfer in the future by helping clinicians identify the embryo with the greatest implantation potential.

Gut microbiota composition can reflect immune responses of latent tuberculosis infection in patients with poorly controlled diabetes.

BACKGROUND: Diabetes mellitus (DM) is a major risk factor for tuberculosis (TB). Evidence has linked the DM-related dysbiosis of gut microbiota to modifiable host immunity to Mycobacterium tuberculosis infection. However, the crosslinks between gut microbiota composition and immunological effects on the development of latent TB infection (LTBI) in DM patients remain uncertain. METHODS: We prospectively obtained stool, blood samples, and medical records from 130 patients with poorly-controlled DM (pDM), defined as ever having an HbA1c > 9.0% within previous 1 year. Among them, 43 had LTBI, as determined by QuantiFERON-TB Gold in-Tube assay. The differences in the taxonomic diversity of gut microbiota between LTBI and non-LTBI groups were investigated using 16S ribosomal RNA sequencing, and a predictive algorithm was established using a random forest model. Serum cytokine levels were measured to determine their correlations with gut microbiota. RESULTS: Compared with non-LTBI group, the microbiota in LTBI group displayed a similar alpha-diversity but different beta-diversity, featuring decrease of Prevotella_9, Streptococcus, and Actinomyces and increase of Bacteroides, Alistipes, and Blautia at the genus level. The accuracy was 0.872 for the LTBI prediction model using the aforementioned 6 microbiome-based biomarkers. Compared with the non-LTBI group, the LTBI group had a significantly lower serum levels of IL-17F (p = 0.025) and TNF-α (p = 0.038), which were correlated with the abundance of the aforementioned 6 taxa. CONCLUSIONS: The study results suggest that gut microbiome composition maybe associated with host immunity relevant to TB status, and gut microbial signature might be helpful for the diagnosis of LTBI.

Conducting the non-inferiority test for the means with unknown coefficient of variation in a three-arm trial.

BACKGROUND: The non-inferiority test is a reasonable approach to assessing a new treatment in a three-arm trial. The three-arm trial consists of a placebo, reference, and an experimental treatment. The non-inferiority is often measured by the mean differences between the experimental and the placebo groups relative to the mean differences between the reference and the placebo groups. METHODS: To cope with possible estimation distortion due to the allowance of heteroskedasticity, we adjust the measurement of non-inferiority by the incorporation of coefficient of variation (CV) of the experimental, the reference and the placebo groups. In this research, we propose a generalized [Formula: see text]-value based method (GPV-based method) to facilitate non-inferiority tests for the means with unknown coefficient of variation in a three-arm trial. RESULTS: The simulation results show that the GPV-based method can not only adequately control type I error rate at nominal level better but also provide power higher than those from Delta method and the empirical bootstrap method, which verifies the feasibility of our adjustment. CONCLUSIONS: We revise the measurement of non-inferiority by deducting the CV of each kind of treatment from the average effect of trials. CVs are included in the non-inferiority explicitly to help prevent possible estimating distortion if heteroskedasticity is allowed. Through the simulation study, the performance of GPV-based method for facilitating non-inferiority tests for the means with unknown CV in a three-arm trial is better than those from empirical bootstrap method and Delta method for small, medium and large sample sizes. Hence, the GPV-based method is recommended to be used to conduct the non-inferiority test for the means with unknown CV in a three-arm trial. The GPV-based method still performs well in non-normality cases.

Development of a specific and sensitive diagnostic PCR for rapid molecular authentication of the medicinal plant Portulaca oleracea.

Adulteration by Bacopa monnieri (BM) in Portulaca oleracea (PO) plants frequently occurs; it decreases the efficacy of traditional Chinese medicine (TCM) and leads to fraud in the herbal marketplace. In this study, a diagnostic PCR assay was established for the rapid authentication of PO and BM in the herbal market. The sequence divergences in internal transcribed spacer 2 (ITS2) between PO and its adulterant species were used to design diagnostic PCR primers. The specific designed primer sets were evaluated and show that the diagnostic PCR assay can be used to verify the authenticity of PO and BM. The detection limits of the primer set for PO and BM identification were 10 pg and 1 pg, respectively. The reactivity of diagnostic PCR was 0.1% PO genomic DNA and 0.01% BM genomic DNA in the test sample during DNA amplification. In addition, multiplex PCR (mPCR) for PO and BM identification was also established. The samples were more susceptible to the effect of steaming in authentication by singleplex PCR and mPCR than boiling and drying treatment. Furthermore, commercial samples from the market were used to demonstrate the applicability of the developed diagnostic PCR for PO authentication and diagnose BM adulteration, and the investigation found that approximately 72.2% (13/18) of PO plants in the herbal market were adulterated. In conclusion, the diagnostic PCR assay was successfully developed and its specificity, sensitivity and reactivity for PO and BM authentication were proven. These developed PCR-based molecular methods can be applied as an identification tool for PO authenticity and can be practically applied for inspection of BM adulteration in the herbal market in the future.

Assessment of Bacillus subtilis fermented Caulerpa microphysa byproduct as feed additive on the growth performance, immune regulation and disease resistance of white shrimp (Litopenaeus vannamei).

In this study, the immunomodulatory and antioxidant activity of fermented Caulerpa microphysa byproduct (FCMB) by Bacillus subtilis was evaluated, and its potential as a feed additive for white shrimp (Litopenaeus vannamei) was explored. In vitro experiments showed that the FCMB supernatant contained polysaccharides, polyphenols and flavonoids, and exhibited antioxidant properties as assessed by various antioxidant assays. Additionally, the FCMB supernatant was found to increase the production rate of reactive oxygen species and the activity of phenoloxidase in hemocytes in vitro. Furthermore, the results of the in vivo feeding trial showed that dietary 5 g kg-1 FCMB significantly improved the weight gain and specific growth rate of white shrimp after 56 days of feeding. Although there were no significant differences in total hemocyte count, phagocytosis, superoxide anion production rate, and phenoloxidase activity among the experimental groups, upregulation of immune-related genes was observed, particularly in the hepatopancreas and hemocytes of shrimps fed with 5 g or 50 g FCMB per kg feed, respectively. In the pathogen challenge assay, white shrimp fed with 5 % FCMB exhibited a higher survival rate compared to the control group following Vibrio parahaemolyticus challenge. Therefore, it is concluded that the fermented byproduct of C. microphysa, FCMB, holds potential as a feed additive for enhancing the growth performance and disease resistance against V. parahaemolyticus in white shrimp.

Association between initial in-hospital heart rate and glycemic control in patients with acute ischemic stroke and diabetes mellitus.

BACKGROUND: A high resting heart rate (HR) has been associated with an increased risk of diabetes mellitus. This study explored the association between initial in-hospital HR and glycemic control in patients with acute ischemic stroke (AIS) and diabetes mellitus. METHODS: We analyzed data from 4,715 patients with AIS and type 2 diabetes mellitus enrolled in the Chang Gung Research Database between January 2010 and September 2018. The study outcome was unfavorable glycemic control, defined as glycated hemoglobin (HbA1c) ≥ 7%. In statistical analyses, the mean initial in-hospital HR was used as both a continuous and categorical variable. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression analysis. The associations between the HR subgroups and HbA1c levels were analyzed using a generalized linear model. RESULTS: Compared with the reference group (HR < 60 bpm), the adjusted ORs for unfavorable glycemic control were 1.093 (95% CI 0.786-1.519) for an HR of 60-69 bpm, 1.370 (95% CI 0.991-1.892) for an HR of 70-79 bpm, and 1.608 (95% CI 1.145-2.257) for an HR of ≥ 80 bpm. Even after adjusting for possible confounders, the HbA1c levels after admission and discharge among diabetic stroke patients increased significantly in the subgroups with higher HRs (p < 0.001). CONCLUSIONS: High initial in-hospital HR is associated with unfavorable glycemic control in patients with AIS and diabetes mellitus, particularly in those with an HR of ≥ 80 bpm, compared with those with an HR of < 60 bpm.

Test-Retest Reliability and Responsiveness of the Computerized Adaptive Testing System of the Functional Assessment of Stroke.

OBJECTIVE: To examine the test-retest reliability, responsiveness, and clinical utility of the Computerized Adaptive Testing System of the Functional Assessment of Stroke (CAT-FAS) in persons with stroke. DESIGN: Repeated measurements design. SETTING: A department of rehabilitation in a medical center. PARTICIPANTS: 30 persons with chronic stroke (for test-retest reliability) and 65 persons with subacute stroke (for responsiveness) were recruited. To examine the test-retest reliability, the participants received measurements twice at 1-month intervals. To examine the responsiveness, the data were collected at admission and discharge from hospital. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASUREMENT TOOL: CAT-FAS. RESULTS: The intra-class correlation coefficients of the CAT-FAS were ≥0.82, indicating good to excellent test-retest reliability. The Kazis' effect size and standardized response mean of the CAT-FAS were ≥0.96, indicating good group-level responsiveness. For individual-level responsiveness, approximately two-thirds of the participants exceeded the conditional minimal detectable change. On average, the CAT-FAS was completed within 9 items and 3 minutes per administration. CONCLUSIONS: Our results suggest the CAT-FAS is an efficient measurement tool with good to excellent test-retest reliability and responsiveness. In addition, the CAT-FAS can be used routinely in clinical settings to monitor progress of the crucial 4 domains for persons with stroke.

Epidemiology and Prehospital Care of Pediatric Unintentional Injuries Among Countries with Different Economic Status in Asia: A Cross-National, Multi-Center Observational Study.

OBJECTIVE: Injury is a major cause of morbidity and mortality in children. However, the epidemiology and prehospital care for pediatric unintentional injuries in Asia are still unclear. METHODS: A total of 9,737 pediatric patients aged <18 years with unintentional injuries cared for at participating centers of the Pan-Asian Trauma Outcome Study (PATOS) from October 2015 to December 2020 were reviewed retrospectively. Patients were divided into two groups: those <8 and those ≥8 years of age. Variables such as patient demographics, injury epidemiology, Injury Severity Score (ISS), and prehospital care were collected. Injury severity and administered prehospital care stratified by gross national income were also analyzed. RESULTS: Pediatric unintentional injuries accounted for 9.4% of EMS-transported trauma cases in the participating Asian centers, and the mortality rate was 0.88%. The leading cause of injury was traffic injuries in older children aged ≥8 years (56.5%), while falls at home were common among young children aged <8 years (43.9%). Compared with younger children, older children with similar ISS tended to receive more prehospital interventions. Uneven disease severity was found in that older children in lower-middle and upper-middle-income countries had higher ISS compared with those in high-income countries. The performance of prehospital interventions also differed among countries with different gross national incomes. Immobilizations were the most performed prehospital intervention followed by oxygen administration, airway management, and pain control; only one patient received prehospital thoracentesis. Procedures were performed more frequently in high-income countries than in upper-middle-income and lower-middle-income countries. CONCLUSIONS: The major cause of injury was road traffic injuries in older children, while falls at home were common among young children. Prehospital care in pediatric unintentional injuries in Asian countries was not standardized and might be insufficient, and the economic status of countries may affect the implementation of prehospital care.