Rapid detection of blood using a novel application of RT-RPA integrated with CRISPR-Cas: ALAS2 detection as a model.

A rapid, sensitive and specific test for blood is reported based on a novel application of recombinase polymerase amplification integrated with CRISPR-Cas and lateral flow assay (LFA). The blood specific marker ALAS2 was used as the target to record the presence of blood. The assay used either RNA extracted from a body fluid as a template, or omitting this extraction step and using a direct approach where the questioned body fluid was added directly to the assay. The assay only detected blood (all peripheral blood and some menstrual blood samples) and no other body fluid (semen, saliva, or vaginal fluid). The limit of detection varied from an initial template of 0.195 ng extracted RNA (27 dilution) or 0.0218 µL (26 dilution) liquid peripheral blood. The assay gave the expected result when peripheral blood was mixed with saliva: ratios of peripheral blood/saliva at 19:1, 3:1, 1:1, 1:3 and 1:19 all gave a positive result using extracted RNA. By contrast, only three ratios of peripheral blood and saliva gave a positive result for blood (19:1, 3:1 and 1:1) when adding these two body fluids directly. When peripheral blood was mixed with semen there was a strong inhibition of the assay and ALAS2 could only be detected at ratio of 19:1 using RNA. Using reconstituted peripheral bloodstains gave comparable results to liquid peripheral blood. This is the first application of RT-RPA integrated CRISPR and combined with a LFA assay to detect body fluid-specific RNA. The proposed method opens up the potential to perform this method remote from laboratories such as at crime scenes.

Renal protective effect of metformin in type 2 diabetes patients.

BACKGROUND: Inhibiting the development and progression of diabetic kidney disease (DKD) is an important issue, but the renoprotective effect of metformin is still controversial. AIMS: To assess the renoprotective effect of metformin in patients with type 2 diabetes. METHODS: This retrospective observational multicenter cohort study included 316,693 patients with type 2 diabetes from seven hospital. After age, gender, medical year, baseline estimated glomerular filtration rate (eGFR), urine protein (dipstick), glycated hemoglobin (HbA1C) and propensity score matching; a total of 13,096 metformin and 13,096 non-metformin patients were included. The main results were doubling of serum creatinine, eGFR ≤ 15 mL/min/1.73 m2 and end stage kidney disease (ESKD). RESULTS: After conducting a multivariable logistic regression analysis on the variables, the metformin group was revealed to have better renal outcomes than non-metformin group, including a lower incidence of doubling of serum creatinine (hazard ratio [HR], 0.71; 95% CI, 0.65-0.77), eGFR ≤ 15 mL/min/1.73 m2 (HR 0.61; 95% CI 0.53-0.71), and ESKD (HR 0.55; 95% CI 0.47-0.66). The subgroup analyses revealed a consistent renoprotective effect across patients with various renal functions. Furthermore, when considering factors such as age, sex, comorbidities, and medications in subgroup analyses, it consistently showed that the metformin group experienced a slower deterioration in renal function across nearly all patient subgroups. CONCLUSIONS: Metformin decreased the risk of renal function deterioration.

TRPS1 expression in breast angiosarcoma.

Angiosarcoma (AS) of the breast, a rare mesenchymal neoplasm, exhibits distinct forms based on etiological and genetic features. While cases with typical clinical presentation and morphology allow for a straightforward diagnosis, challenges arise when clinical data are scarce, diagnostic material is limited, or morphological characteristics overlap with other tumors, including undifferentiated carcinomas. The trichorhinophalangeal syndrome protein 1 (TRPS1), once regarded as highly specific for breast carcinomas, now faces doubts regarding its reliability. This study explores TRPS1 expression in breast AS. Our investigation revealed that 60% of AS cases displayed TRPS1 labeling, contrasting with the 40% lacking expression. Scoring by four independent readers established a consensus, designating 12/35 ASs as unequivocally TRPS1-positive. However, uncertainty surrounded nine further cases due to a lack of reader agreement (being substantial as reflected by a kappa value of 0.76). These findings challenge the perceived specificity of TRPS1, shedding light on its presence in a noteworthy proportion of breast ASs. Consequently, the study underscores the importance of a comprehensive approach in evaluating breast ASs and expands the range of entities within the differential diagnosis associated with TRPS1 labeling.

Role of Peritoneal Equilibration Test in Assessing Folate Transport During Peritoneal Dialysis.

OBJECTIVES: Low plasma folate levels have been reported in patients undergoing hemodialysis and peritoneal dialysis (PD) in clinical studies. However, folate transport has never been mentioned as a factor contributing to low plasma folate levels in patients undergoing PD. The peritoneal equilibrium test (PET) assesses the plasma creatinine level and glucose transport abilities. This study aimed to evaluate the association between plasma folate levels and folate transport during PD based on PET grades. METHODS: This study recruited 50 patients who underwent PD for ≥3 months and were categorized according to PET grades. Data regarding plasma folate levels and dialysate folate were collected. The primary outcomes were the relationship between the PET grade and plasma folate level and between the PET grade and dialysate-to-plasma folate concentration ratio (D/P folate). Furthermore, the difference in the plasma folate level and D/P folate between men and women was assessed. RESULTS: The plasma folate level and the D/P folate significantly differed among the 4 PET groups (both P < .001). PET grade was significantly negatively correlated with plasma folate levels (r = -0.56, P < .001) and positively correlated with D/P folate (r = 0.686, P < .001). In subgroup analysis, neither the plasma folate level nor the D/P folate significantly differed between men and women. CONCLUSIONS: Our study provides clinical evidence that the PET grade is associated with the plasma folate level and D/P folate, regardless of sex. Larger cohort studies are warranted to assess the importance of folate supplementation during PD based on PET grades.

Ten-year epidemiology and risk factors of cytomegalovirus infection in hematopoietic stem cell transplantation patients in Taiwan.

BACKGROUND: Cytomegalovirus (CMV) can cause infection and critical diseases in hematopoietic stem cell transplantation (HSCT) recipients. This study aimed to explore the cumulative incidence and risk factors for CMV infection and disease among HSCT recipients in Taiwan. METHODS: This retrospective cohort study using the Taiwan Blood and Marrow Transplantation Registry (TBMTR) included HSCT recipients between 2009 and 2018 in Taiwan. The primary outcome was cumulative incidence of CMV infection or disease at day 100 after HSCT. Secondary outcomes included day 180 cumulative incidence of CMV infection or disease, infection sites, risk factors for CMV infection or disease, survival analysis, and overall survival after CMV infection and disease. RESULTS: There were 4394 HSCT recipients included in the study (2044 auto-HSCT and 2350 allo-HSCT). The cumulative incidence of CMV infection and disease was significantly higher in allo-HSCT than in auto-HSCT patients at day 100 (53.7% vs. 6.0%, P < 0.0001 and 6.1% vs. 0.9%, P < 0.0001). Use of ATG (HR 1.819, p < 0.0001), recipient CMV serostatus positive (HR 2.631, p < 0.0001) and acute GVHD grades ≥ II (HR 1.563, p < 0.0001) were risk factors for CMV infection, while matched donor (HR 0.856, p = 0.0180) and myeloablative conditioning (MAC) (HR 0.674, p < 0.0001) were protective factors. CONCLUSION: The study revealed a significant disparity in terms of the incidence, risk factors, and clinical outcomes of CMV infection and disease between auto and allo-HSCT patients. These findings underscore the importance of considering these factors in the management of HSCT recipients to improve outcomes related to CMV infections.

Ultrasensitive and Rapid Detection of Procalcitonin via Waveguide-Enhanced Nanogold-Linked Immunosorbent Assay for Early Sepsis Diagnosis.

Sepsis, a life-threatening inflammatory response, demands economical, accurate, and rapid detection of biomarkers during the critical "golden hour" to reduce the patient mortality rate. Here, we demonstrate a cost-effective waveguide-enhanced nanogold-linked immunosorbent assay (WENLISA) based on nanoplasmonic waveguide biosensors for the rapid and sensitive detection of procalcitonin (PCT), a sepsis-related inflammatory biomarker. To enhance the limit of detection (LOD), we employed sandwich assays using immobilized capture antibodies and detection antibodies conjugated to gold nanoparticles to bind the target analyte, leading to a significant evanescent wave redistribution and strong nanoplasmonic absorption near the waveguide surface. Experimentally, we detected PCT for a wide linear response range of 0.1 pg/mL to 1 ng/mL with a record-low LOD of 48.7 fg/mL (3.74 fM) in 8 min. Furthermore, WENLISA has successfully identified PCT levels in the blood plasma of patients with sepsis and healthy individuals, offering a promising technology for early sepsis diagnosis.

Correlation Analyses between Histological Staging and Molecular Alterations in Tumor-Derived and Cell-Free DNA of Early-Stage Primary Cutaneous Melanoma.

Here, we investigate the correlation and statistical analyses between histological staging and molecular alterations in tumor-derived (tdDNA) and cell-free DNA (cfDNA) obtained from early-stage primary cutaneous melanoma (PCM) patients using digital PCR (dPCR) for the detection of the BRAF p.V600E somatic pathogenic variant. In the prospective study, a total of 68 plasma and paired tdDNA samples, and in the retrospective cohort, a total of 100 tdDNA samples were analyzed using dPCR and reverse hybridization StripAssay. The Breslow depth (BD) and Clark level were applied to categorize the study population. Our results demonstrate that dPCR is a highly sensitive and specific method for the detection of BRAF p.V600E somatic variants in cfDNA samples from PCM patients. A strong correlation was detected between BD and cfDNA concentration in all mutant and negative cases, between the tdDNA concentration and the tumor-derived variant allele frequency (VAF) of BRAF p.V600E, between the tdVAF and the cfVAF in all cases, and between the cfDNA and cfVAF in mutant cases. The tdVAF and cfVAF of BRAF p.V600E and cfDNA concentration were the highest in Clark's V category. The cfDNA concentration was statistically significantly higher in Clark's III, IV, and V groups compared to cases with a better prognosis. It can also be explained by the fact that cases with a more advanced stage classification release more cfDNA into the peripheral circulation.

Phosphate burden induces vascular calcification through a NLRP3-caspase-1-mediated pyroptotic pathway.

AIMS: The aim of this study is to clarify the role of NLRP3 inflammasome in phosphate burden-induced vascular smooth muscle cell (VSMC) calcification. MAIN METHODS: VSMC calcification was induced using a high concentration of inorganic phosphate. After pharmacological inhibition or genetic silencing of the NLRP3 inflammasome, pyroptosis, or potassium efflux, the cells were examined by RT-qPCR, immunofluorescence, and western blotting to identify the NLRP3-mediated pathway for VSMC calcification. KEY FINDINGS: Calcified VSMCs with α-smooth muscle actin (α-SMA) disarray presented features of pyroptosis, including caspase-1 maturation, cleaved gasdermin D (GSDMD), and a high supernatant level of lactate dehydrogenase A. Pharmacological inhibitions of caspase-1 and pyroptosis attenuated VSMC calcification, whereas interleukin-1ß receptor antagonism did not. Unlike canonical NLRP3 activation, osteogenic VSMCs did not upregulate NLRP3 expression. However, NLRP3 genetic silencing or inhibitions, which targets different domains of the NLRP3 protein, could ameliorate VSMC calcification by aborting caspase-1 and GSDMD activation. Furthermore, potassium efflux through the inward-rectifier potassium channel, and not through the P2X7 receptor, triggered NLRP3 inflammasome activation and VSMC calcification. SIGNIFICANCE: In the present study, we identified a potassium efflux-triggered NLRP3-caspase-1-mediated pyroptotic pathway for VSMC calcification that is unique and different from the canonical NLRP3 inflammasome activation. Therefore, targeting this pathway may serve as a novel therapeutic strategy for vascular calcification.

Mechanically Robust Interface at Metal/Muscovite Quasi van der Waals Epitaxy.

Quasi van der Waals epitaxy is an approach to constructing the combination of 2D and 3D materials. Here, we quantify and discuss the 2D/3D interface structure and the corresponding features in metal/muscovite systems. High-resolution scanning transmission electron microscopy reveals the atomic arrangement at the interface. The theoretical results explain the formation mechanism and predict the mechanical robustness of these metal/muscovite quasi van der Waals epitaxies. The evidence of superior interface quality is delivered according to the outstanding performance of the designed systems in both retention (>105 s) and cycling tests (>105 cycles) through electromechanical measurements. With high-temperature X-ray reciprocal space mapping, the unique anisotropy of thermal expansion is discovered and predicted to sustain the thermal stress with a sizable thermal actuation. A maximum bending curvature of 264 m-1 at 243 °C can be obtained in the silver/muscovite heteroepitaxy. The electrothermal and photothermal methods show a fast response to thermal stress and demonstrate the interface robustness.

Developing an automatic warning system for anomalous chicken dispersion and movement using deep learning and machine learning.

Chicken is a major source of dietary protein worldwide. The dispersion and movement of chickens constitute vital indicators of their health and status. This is especially evident in Taiwanese native chickens (TNCs), a local variety which is high in physical activity when healthy. Conventionally, the dispersion and movement of chicken flocks are observed in patrols. However, manual patrolling is laborious and time-consuming. Moreover, frequent patrols increase the risk of carrying pathogens into chicken farms. To address these issues, this study proposes an approach to develop an automatic warning system for anomalous dispersion and movement of chicken flocks in commercial chicken farms. Embendded systems were developed to acquire videos of chickens from overhead view in a chicken house, in which approximately 20,000 TNCs were raised for a period of 10 wk. Each video was 5-min in length. The videos were transmitted to a remote cloud server and were converted into images. A You Only Look Once-version 7 tiny (YOLOv7-tiny) object detection model was trained to detect chickens in the images. The dispersion of the chicken flocks in a 5-min long video was calculated using nearest neighbor index (NNI). The movement of the chicken flocks in a 5-min long video was quantified using simple online and real-time tracking algorithm (SORT). The normal ranges (i.e., 95% confidence intervals) of chicken dispersion and movement were established using an autoregressive integrated moving average (ARIMA) model and a seasonal autoregressive integrated moving average with exogenous factors (SARIMAX) model, respectively. The system allows farmers to check up on the chicken farm only when the dispersion or movement values were not in the normal ranges. Thus, labor time can be saved and the risk of carrying pathogens into chicken farms can be reduced. The trained YOLOv7-tiny model achieved an average precision of 98.2% in chicken detection. SORT achieved a multiple object tracking accuracy of 95.3%. The ARIMA and SARIMAX achieved a mean absolute percentage error 3.71% and 13.39%, respectively, in forecasting dispersion and movement. The proposed approach can serve as a solution for automatic monitoring of anomalous chicken dispersion and movement in chicken farming, alerting farmers of potential health risks and environmental hazards in chicken farms.

Examining Health Literacy in Taiwanese Smoking Cessation Populations: A Multidimensional Evaluation of Sociodemographic Factors and Domain-Specific Competencies.

BACKGROUND: Cigarette smoking is a serious global health issue. Limited studies previously analyzed health literacy components in patients undergoing smoking cessation interventions. This study focuses on individuals enrolled in smoking cessation services and investigates the distribution of health literacy in three domains (health care, disease prevention, and health promotion) and four abilities (access, understand, appraise, and apply health information). The study also explores the correlation between background factors (age, BMI, etc.) and health literacy, as well as the differences in health literacy levels among different background variables (gender, etc.). METHODS: 228 individuals completed the health literacy questionnaire. Descriptive statistical analysis, Pearson Correlation, and a Chi-Squared Test were employed to investigate the various health literacy levels and background variables. RESULTS: 68% had excellent or sufficient health literacy. A total of 32% were considered problematic or to have inadequate health literacy. Of the three domains of health literacy, participants performed better in the healthcare domain. More than one-third were problematic in accessing and appraising information. CONCLUSIONS: this paper, being the pilot study in providing an analysis of health literacy components in individuals undergoing smoking cessation, could serve as a useful reference for devising interventions for different population groups in trying to maximize successful cessation rates.

[Penile epithelioid hemangioma]. / A hímvesszo epithelioid haemangiomája.

Epithelioid hemangioma is a benign vascular tumor. Complete surgical excision is curative, there is no tendency to recurrence or metastasize. Its penile occurrence is extremely rare, only 33 cases have been reported in English literature. A patient with epithelioid hemangioma of the deep dorsal vein of the penis is reported. To our knowledge, this is the first report of penile epithelioid hemangioma in Hungarian literature. The 64-year-old patient presented to our department with painful erection caused by a palpable penile mass. Physical examination revealed a mobile subcutaneous nodule on the dorsum of the penis. Penile ultrasound showed a 10 mm homogeneous, well circumscribed lesion superficial to the tunica albuginea of the corpora cavernosa without intralesional blood flow. Local excision was performed through a dorsal longitudinal penile incision. The deep dorsal vein was dissected circumferentially, then the lesion was removed following ligation of the vein proximal and distal to the mass. Histopathological examination revealed epithelioid hemangioma. At three months after surgery, the patient reported complete resolution of pain, his International Index of Erectile Function Score was 21. At four years after the operation, there were no signs of recurrence or metastasis. Successful treatment of epithelioid hemangioma of the penis requires in-depth knowledge of processes resulting in penile subcutaneous masses, therefore the differential diagnosis is detailed in discussion. Orv Hetil. 2023; 164(21): 836-840.

Evaluation of the Impact of Remote Monitoring Using the Sharesource Connectivity Platform on Adherence to Automated Peritoneal Dialysis in 51 Patients.

BACKGROUND This study from a single center in Taiwan aimed to evaluate the impact of remote patient monitoring (RPM) using the Sharesource connectivity platform on adherence to automated peritoneal dialysis (APD) in 51 patients. MATERIAL AND METHODS We analyzed data on 51 patients with end-stage renal disease (ESRD) under APD. They were treated with a traditional APD machine HomeChoice (phase 1), changed to new APD machine HomeChoice Claria for 12 weeks (phase 2), then connected to the Sharesource platform for another 12 weeks (phase 3), and were followed up for 1 year. The non-adherence rate was compared between the 3 phases. The secondary outcomes included peritonitis rate, hospitalization rate, and hospitalization days, 1 year before and after receiving a new APD machine. Patients were subdivided into good and poor adherence (>1 episode of non-adherence in phase 1) groups for further analysis. RESULTS The average non-adherence rates were 10.5%, 5.1%, and 4.9% in phases 1, 2, and 3, respectively, although differences were not significant. Serum potassium (P<0.0001) and C-reactive protein (CRP) (P=0.026) levels significantly decreased in phase 3. The 1-year peritonitis rate, hospitalization rate, and number of days of hospitalization showed no significant changes. Subgroup analysis revealed that the non-adherence rate in the poor adherence group decreased from 48.4% in phase 1 to 14.2% and 12.4% in phases 2 and 3, respectively (P=0.007). CONCLUSIONS Remoting monitoring using the Sharesource connectivity platform increased dialysis adherence in APD treatment, especially in patients with poor adherence. Serum potassium level and inflammation status were also improved by this system.

Molecular Identification and In Silico Protein Analysis of a Novel BCOR-CLGN Gene Fusion in Intrathoracic BCOR-Rearranged Sarcoma.

BCOR (BCL6 corepressor)-rearranged sarcomas (BRSs) are a heterogeneous group of sarcomas previously classified as part of the group of "atypical Ewing" or "Ewing-like" sarcomas, without the prototypical ESWR1 gene translocation. Due to their similar morphology and histopathological features, diagnosis is challenging. The most common genetic aberrations are BCOR-CCNB3 fusion and BCOR internal tandem duplication (ITD). Recently, various new fusion partners of BCOR have been documented, such as MAML3, ZC3H7B, RGAG1, and KMT2D, further increasing the complexity of such tumor entities, although the molecular pathogenetic mechanism remains to be elucidated. Here, we present an index case of intrathoracic BRS that carried a novel BCOR-CLGN (calmegin) gene fusion, exhibited by a 52-year-old female diagnosed initially by immunohistochemistry due to the positivity of a BCOR stain; the fusion was identified by next-generation sequencing and was confirmed by Sanger sequencing. In silico protein analysis was performed to demonstrate the 3D structure of the chimera protein. The physicochemical properties of the fusion protein sequence were calculated using the ProtParam web-server tool. Our finding further broadens the fusion partner gene spectrum of BRS. Due to the heterogeneity, molecular ancillary tests serve as powerful tools to discover these unusual variants, and an in silico analysis of the fusion protein offers an appropriate approach toward understanding the exact pathogenesis of such a rare variant.

All-Cause Standardized Mortality Ratio in Hemodialysis and Peritoneal Dialysis Patients: A Nationwide Population-Based Cohort Study.

Patients with end-stage renal disease (ESRD) are at a higher mortality risk compared with the general population. Previous studies have described a relationship between mortality and patients with ESRD, but the data on standardized mortality ratio (SMR) corresponding to different causes of death in patients undergoing hemodialysis (HD) and peritoneal dialysis (PD) are limited. This study was designed as a nationwide population-based retrospective cohort study. Incident dialysis patients between January 2000 and December 2015 in Taiwan were included. Using data acquired from the Taiwan Death Registry, SMR values were calculated and compared with the overall survival. The results showed there were a total of 128,966 patients enrolled, including 117,376 incident HD patients and 11,590 incident PD patients. It was found that 75,297 patients (58.4%) died during the period of 2000-2017. The overall SMR was 5.21. The neoplasms SMR was 2.11; the endocrine, nutritional, metabolic, and immunity disorders SMR was 13.53; the circulatory system SMR was 4.31; the respiratory system SMR was 2.59; the digestive system SMR was 6.1; and the genitourinary system SMR was 27.22. Therefore, more attention should be paid to these diseases in clinical care.

Description of Photodegradation Mechanisms and Structural Characteristics in Carbon@Titania Yolk-Shell Nanostructures by XAS.

Carbon@titania yolk-shell nanostructures are successfully synthesized at different calcination conditions. These unique structure nanomaterials can be used as a photocatalyst to degrade the emerging water pollutant, acetaminophen (paracetamol). The photodegradation analysis studies have shown that the samples with residual carbon nanospheres have improved the photocatalytic efficiency. The local electronic and atomic structure of the nanostructures are analyzed by X-ray absorption spectroscopy (XAS) measurements. The spectra confirm that the hollow shell has an anatase phase structure, slight lattice distortion, and variation in Ti 3d orbital orientation. In situ XAS measurements reveal that the existence of amorphous carbon nanospheres inside the nano spherical shell inhibit the recombination of electron-hole pairs; more mobile holes are formed in the p-d hybridized bands near the Fermi surface and enables the acceleration of the carries that significantly enhance the photodegradation of paracetamol under UV-visible irradiation. The observed charge transfer process from TiO2  hybridized orbital to the carbon nanospheres reduces the recombination rate of electrons and holes, thus increasing the photocatalytic efficiency.

Cutaneous metastases at the sites of pembrolizumab-induced bullous pemphigoid lesions in a patient with melanoma.

The authors report a case of bullous pemphigoid (BP) that occurred during pembrolizumab therapy in a 67-year-old male patient with advanced melanoma. Following regression of BP blisters, they reintroduced anti-PD-1 treatment. Due to the flare-up of BP, immunotherapy was discontinued again and corticosteroid was restarted. As the BP lesions regressed, interestingly, new skin metastases developed, exactly where the blisters were. One year after discontinuation of anti-PD-1 treatment, considering the significant tumor progression, pembrolizumab was restarted. This induced tumor remission, while the added low-dose corticosteroid was able to prevent the recurrence of BP. The patient carries the BP-predisposing HLA-DQB1*03:01 allele. In conclusion, anti-PD-1 rechallenge may be considered in metastatic melanoma, even if restarting anti-PD-1 has previously caused the flare-up of BP symptoms.

Immune checkpoint inhibitors prolong the survival of patients with metastatic melanoma. Bullous pemphigoid (BP) is a rare, cutaneous, immune-related adverse event. The authors report a case of BP that occurred during pembrolizumab therapy in a 67-year-old male patient with advanced melanoma who responded to anti-PD-1 treatment with a partial response. Following the resolution of BP symptoms, pembrolizumab treatment was restarted after discontinuation of systemic corticosteroid therapy. Due to the flare-up of BP, anti-PD-1 treatment was discontinued and steroid therapy was restarted; however, skin metastases soon developed, exactly where the BP blisters were. Pembrolizumab rechallenge was successful in inducing the complete regression of skin metastases, while the added low-dose corticosteroid was able to prevent the recurrence of BP.

Long-term mortality rates of young stroke in Taiwan: A decade-long epidemiology population-based study.

Introduction: Stroke remains a leading cause of death worldwide. Stroke in young adults is an important issue, gaining extra attention in recent years. This study aims to investigate the mortality after stroke in young adults in Taiwan. Patients and methods: This is a registry- and population-based study in Taiwan of patients aged 20-50 years with first-ever stroke between 1999 and 2012, with follow-up until January 1, 2022. Patients and mortalities were identified through Taiwan National Health Insurance database. Results: The study population included 65,097 patients with stroke (mean age, 42.6 ± 6.6 years; 30.5% woman). There were 23,481 (36.1%) intracranial hemorrhage, 37,522 (57.6%) ischemic stroke, and 4094 (6.3%) stroke not otherwise specified. At the end of follow-up, a total of 18,248 deaths (28.0%) occurred during a median follow-up of 9.8 years (interquartile range, 6.4-13.7 years). Conclusion: Taiwan young adults who were 30-day survivors of first-ever stroke have significantly higher long-term mortality rates when compared to other population-based studies.

A Novel Immune-Related Gene Prognostic Index (IRGPI) in Pancreatic Adenocarcinoma (PAAD) and Its Implications in the Tumor Microenvironment.

PURPOSE: Pancreatic adenocarcinoma (PAAD) is one of the most lethal malignancies, with less than 10% of patients surviving more than 5 years. Existing biomarkers for reliable survival rate prediction need to be enhanced. As a result, the objective of this study was to create a novel immune-related gene prognostic index (IRGPI) for estimating overall survival (OS) and to analyze the molecular subtypes based on this index. Materials and procedures: RNA sequencing and clinical data were retrieved from publicly available sources and analyzed using several R software packages. A unique IRGPI and optimum risk model were developed using a machine learning algorithm. The prediction capability of our model was then compared to that of previously proposed models. A correlation study was also conducted between the immunological tumor microenvironment, risk groups, and IRGPI genes. Furthermore, we classified PAAD into different molecular subtypes based on the expression of IRGPI genes and investigated their features in tumor immunology using the K-means clustering technique. RESULTS: A 12-gene IRGPI (FYN, MET, LRSAM1, PSPN, ERAP2, S100A1, IL20RB, MAP3K14, SEMA6C, PRKCG, CXCL11, and GH1) was established, and verified along with a risk model. OS prediction by our model outperformed previous gene signatures. According to the findings of our correlation studies, different risk groups and IRGPI genes were found to be tightly related to tumor microenvironments, and PAAD could be further subdivided into immunologically distinct molecular subtypes based on the expression of IRGPI genes. CONCLUSION: The current study constructed and verified a unique IRGPI. Furthermore, our findings revealed a connection between the IRGPI and the immunological microenvironment of tumors. PAAD was differentiated into several molecular subtypes that might react differently to immunotherapy. These findings could provide new insights for precision and translational medicine for more innovative immunotherapy strategies.

The use of a low-flux hemo-dialyzer is associated with impaired platelet aggregation in patients undergoing chronic hemodialysis.

In patients with chronic hemodialysis (HD), both abnormal thrombotic and bleeding events are commonly observed. Uremic platelet dysfunction is one of the important attributing factors. Moreover, HD may also result in aggregation dysfunction of platelets during the therapeutic procedure. However, how the HD process affects platelet and coagulation function is unknown and dialyzer membrane flux could have an impact on it. We aimed to compare the impacts of low-flux and high-flux HD on the platelet function of patients undergoing chronic HD. This was a cross-sectional study conducted in the HD unit of E-Da hospital in Taiwan. A total of 78 patients with maintenance HD three times per week for more than one year, including 40 with high- and 38 with low-flux hemodialysis, were recruited. Their platelet functions were evaluated using an in vitro platelet function analyzer (PFA-100) before and after the HD session. Of the 78 patients undergoing HD, 60 (76%) had prolonged pre-dialysis collagen/epinephrine (CEPI) and collagen/adenosine diphosphate closure times. Those receiving low-flux dialyzer had a significant increase in CEPI closure time (pre-dialysis 212.3 ±â€…62.1 seconds. post-dialysis 241.5 ±â€…64.3 seconds, P = .01), but not collagen/adenosine diphosphate closure time, after HD. After adjusting confounding factors, only the low-flux dialyzer demonstrated an independent association with the prolonged CEPI closure time after HD therapy (odds ratio = 23.31, 95% CI: 1.94-280.61, P = .01). We observed that impaired platelet aggregation is prevalent in patients undergoing chronic HD. Therefore, the use of low-flux dialyzers may further worsen platelet aggregation after dialysis. Patients with uremic bleeding diathesis should take precautions. We suggest that further studies using flow cytometry should be conducted to explore the mechanism of dialysis flux and platelet activity during HD.