Optofluidic time-stretch imaging flow cytometry with a real-time storage rate beyond 5.9 GB/s.

Optofluidic time-stretch imaging flow cytometry (OTS-IFC) provides a suitable solution for high-precision cell analysis and high-sensitivity detection of rare cells due to its high-throughput and continuous image acquisition. However, transferring and storing continuous big data streams remains a challenge. In this study, we designed a high-speed streaming storage strategy to store OTS-IFC data in real-time, overcoming the imbalance between the fast generation speed in the data acquisition and processing subsystem and the comparatively slower storage speed in the transmission and storage subsystem. This strategy, utilizing an asynchronous buffer structure built on the producer-consumer model, optimizes memory usage for enhanced data throughput and stability. We evaluated the storage performance of the high-speed streaming storage strategy in ultra-large-scale blood cell imaging on a common commercial device. The experimental results show that it can provide a continuous data throughput of up to 5891 MB/s.

Modulating the Structure and Optoelectronic Properties of Solution-Processed Bismuth-Based Nanocrystals.

Bismuth-based chalcogenides have emerged as promising candidates for next-generation, solution-processable semiconductors, mainly benefiting from their facile fabrication, low cost, excellent stability, and tunable optoelectronic properties. Particularly, the recently developed AgBiS2 solar cells have shown striking power conversion efficiencies. High performance bismuth-based photodetectors have also been extensively studied in the past few years. However, the fundamental properties of these Bi-based semiconductors have not been sufficiently investigated, which is crucial for further improving the device performance. Here, we introduce multiple time-resolved and steady-state techniques to fully characterize the charge carrier dynamics and charge transport of solution-processed Bi-based nanocrystals. It was found that the Ag-Bi ratio plays a critical role in charge transport. For Ag-deficient samples, silver bismuth sulfide thin films behave as localized state induced hopping charge transport, and the Ag-excess samples present band-like charge transport. This finding is crucial for developing more efficient Bi-based semiconductors and optoelectronic devices.

MOF-derived nanozyme CuOx@C and its application for cascade colorimetric detection of phytosterols.

Phytosterols (PSs), a class of naturally occurring bioactive lipid compounds, have been found to possess a significant cholesterol-lowering effect. In developing countries, the consumption of rapeseed oil is the primary pathway of PS intake for the general population. However, developing low-cost, real-time, and high-throughput screening techniques for PSs remains a challenge. Here, a Cu-based nanocomposite CuOx@C was synthesized via a simple method of the calcination of HKUST-1 and systematically characterized by scanning electron microscopy, transmission electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. The CuOx@C demonstrated excellent peroxidase-like (POD-like) activity, functioning as a peroxidase mimic to facilitate the catalysis of 3,3',5,5'-tetramethylbenzidine (TMB) into its oxidized form (oxTMB), thereby initiating a discernible color response. On the basis of this discovery, a CuOx@C-based colorimetric method for detecting total sterols in rapeseed was successfully constructed via cascade reactions. After optimizing the conditions, the high-throughput screening of total sterols in rapeseed could be completed in only 21 min, which significantly facilitated the sensing of PSs. A linear range of 0.6-6 mg/g was achieved for the detection of total sterols in rapeseed samples, thereby satisfying the requirements for detection. In addition, due to the high stability of CuOx@C and the specificity of cholesterol oxidase, the developed method had excellent stability and selectivity toward PSs, indicating that this work has huge prospects for commercial application. This innovative work overcomes the limitation of the instrumental method and provides a portable and reliable tool for total sterols detection. It can also facilitate the development of oilseeds with a high content of PSs.

Effects of circulating inflammatory proteins on osteoporosis and fractures: evidence from genetic correlation and Mendelian randomization study.

Objective: There is a controversy in studies of circulating inflammatory proteins (CIPs) in association with osteoporosis (OP) and fractures, and it is unclear if these two conditions are causally related. This study used MR analyses to investigate the causal associations between 91 CIPs and OP and 9 types of fractures. Methods: Genetic variants data for CIPs, OP, and fractures were obtained from the publicly available genome-wide association studies (GWAS) database. We used inverse variance weighted (IVW) as the primary analysis, pleiotropy, and heterogeneity tests to analyze the validity and robustness of causality and reverse MR analysis to test for reverse causality. Results: The IVW results with Bonferroni correction indicated that CXCL11 (OR = 1.2049; 95% CI: 1.0308-1.4083; P = 0.0192) can increase the risk of OP; IL-4 (OR = 1.2877; 95% CI: 1.1003-1.5070; P = 0.0016), IL-7 (OR = 1.2572; 95% CI: 1.0401-1.5196; P = 0.0180), IL-15RA (OR = 1.1346; 95% CI: 1.0163-1.2668; P = 0.0246), IL-17C (OR = 1.1353; 95% CI: 1.0272-1.2547; P = 0.0129), CXCL10 (OR = 1.2479; 95% CI: 1.0832-1.4377; P = 0.0022), eotaxin/CCL11 (OR = 1.1552; 95% CI: 1.0525-1.2678; P = 0.0024), and FGF23 (OR = 1.9437; 95% CI: 1.1875-3.1816; P = 0.0082) can increase the risk of fractures; whereas IL-10RB (OR = 0.9006; 95% CI: 0.8335-0.9730; P = 0.0080), CCL4 (OR = 0.9101; 95% CI: 0.8385-0.9878; P = 0.0242), MCP-3/CCL7 (OR = 0.8579; 95% CI: 0.7506-0.9806; P = 0.0246), IFN-γ [shoulder and upper arm (OR = 0.7832; 95% CI: 0.6605-0.9287; P = 0.0049); rib(s), sternum and thoracic spine (OR = 0.7228; 95% CI: 0.5681-0.9197; P = 0.0083)], ß-NGF (OR = 0.8384; 95% CI: 0.7473-0.9407; P = 0.0027), and SIRT2 (OR = 0.5167; 95% CI: 0.3296-0.8100; P = 0.0040) can decrease fractures risk. Conclusion: Mendelian randomization (MR) analyses indicated the causal associations between multiple genetically predicted CIPs and the risk of OP and fractures.

Contributions of Common Foods to Resveratrol Intake in the Chinese Diet.

Resveratrol is a polyphenolic compound with antioxidant and anti-inflammatory properties and therefore has potential health benefits for the prevention and treatment of a wide range of diseases, including cardiovascular disease, cancer, diabetes, and neurodegenerative diseases. The beneficial dose of resveratrol is between 30 and 150 mg. Although the health benefits of resveratrol have been extensively studied, resveratrol intake through the diet of residents in China remains unclear, which restricts the development of resveratrol-rich foods. In this study, a dietary assessment was conducted to reveal that the daily resveratrol intake by Chinese residents through common foods was only 0.783 mg, which was significantly below the beneficial dose. Among the main food types, fruits emerged as the primary source of resveratrol, contributing to 88.35% of the total intake. To improve resveratrol intake, potential methods to increase its consumption were proposed. First method is to increase the resveratrol content of fruits and peanuts. In addition, resveratrol can be extracted from peels. It is also recommended to adopt technical means to improve the bioavailability of resveratrol and develop related supplements and functional drinks.

Comprehensive multi-omics analysis of resectable locally advanced gastric cancer: Assessing response to neoadjuvant camrelizumab and chemotherapy in a single-center, open-label, single-arm phase II trial.

BACKGROUND: The current standard of care for locally advanced gastric cancer (GC) involves neoadjuvant chemotherapy followed by radical surgery. Recently, neoadjuvant treatment for this condition has involved the exploration of immunotherapy plus chemotherapy as a potential approach. However, the efficacy remains uncertain. METHODS: A single-arm, phase 2 study was conducted to evaluate the efficacy and tolerability of neoadjuvant camrelizumab combined with mFOLFOX6 and identify potential biomarkers of response through multi-omics analysis in patients with resectable locally advanced GC. The primary endpoint was the pathological complete response (pCR) rate. Secondary endpoints included the R0 rate, near pCR rate, progression-free survival (PFS), disease-free survival (DFS), and overall survival (OS). Multi-omics analysis was assessed by whole-exome sequencing, transcriptome sequencing, and multiplex immunofluorescence (mIF) using biopsies pre- and post-neoadjuvant therapy. RESULTS: This study involved 60 patients, of which 55 underwent gastrectomy. Among these, five (9.1%) attained a pathological complete response (pCR), and 11 (20.0%) reached near pCR. No unexpected treatment-emergent adverse events or perioperative mortality were observed, and the regimen presented a manageable safety profile. Molecular changes identified through multi-omics analysis correlated with treatment response, highlighting associations between HER2-positive and CTNNB1 mutations with treatment sensitivity and a favourable prognosis. This finding was further supported by immune cell infiltration analysis and mIF. Expression data uncovered a risk model with four genes (RALYL, SCGN, CCKBR, NTS) linked to poor response. Additionally, post-treatment infiltration of CD8+ T lymphocytes positively correlates with pathological response. CONCLUSION: The findings suggest the combination of PD-1-inhibitor and mFOLFOX6 showed efficacy and acceptable toxicity for locally advanced GC. Extended follow-up is required to determine the duration of the response. This study lays essential groundwork for developing precise neoadjuvant regimens.

The causal relationship between psoriasis and cancers: a two-sample Mendelian randomization analysis.

Background: Although observational studies suggest a correlation between psoriasis (PS) and cancers, it is still unknown whether this association can replace causal relationships due to the limitations of observational studies. Therefore, we conducted a two-sample Mendelian randomization (MR) analysis to evaluate the causal relationship between PS and cancers. Methods: PS genetic summary data were obtained from two genome-wide association studies (GWAS). We employed MR Base for individuals retrieving tumors from distinct locations. Inverse-variance weighted analysis was the principal method used for MR, supplemented by weighted median, MR Egger, simple mode, and weighted mode. To investigate the possible link between psoriasis and cancers, we performed two independent two-sample MR studies and a meta-analysis based on two independent MR analyses. Results: Two independent MR analyses both found no significant causal relationship between PS and overall cancers (OR=1.0000, 95% confidence interval [CI]:0.9999-1.0001, P=0.984; OR=1.0000, 95% CI:0.9999-1.0001, P=0.761), and no significant causal relationship with 17 site-specific cancers. In the meta-analysis conducted by two two-sample MR analyses, there was no significant causal relationship between PS and overall cancers (OR=1.0000, 95% CI: 0.9999-1.0001, P=1.00, I 2 = 0.0%), and there was no significant causal relationship with 17 site-specific cancers. Conclusions: Our findings do not support a genetic link between PS and cancers. More population-based and experimental investigations will be required better to understand the complicated relationship between PS and cancers.

Comparison of Thulium Fiber Laser versus Holmium laser in ureteroscopic lithotripsy: a Meta-analysis and systematic review.

OBJECTIVES: To compare the efficacy and safety of thulium fiber laser (TFL) to holmium: YAG (Ho: YAG) laser in ureteroscopic lithotripsy for urolithiasis. METHODS: PubMed, Web of Science, Embase, CENTRAL, SinoMed, CNKI database, VIP and Wanfang Database were systematically searched for all relevant clinical trials until September 2023. References were explored to identify the relevant articles. Meta-analysis was carried out for the retrieved studies using RevMan5.4.1 software, and the risk ratio, mean difference and 95% confidence interval were expressed. Statistical significance was set at p < 0.05. The main outcomes of this meta-analysis were stone-free rate (SFR), perioperative outcomes and intraoperative or postoperative complications. RESULTS: Thirteen studies, including 1394 patients, were included. According to the results of pooled analysis, TFL was associated with significantly higher stone-free rate (SFR) [0.52, 95% CI (0.32, 0.85), P = 0.009], shorter operation time [-5.47, 95% CI (-8.86, -2.08), P = 0.002], and less stone migration [0.17, 95% CI (0.06, 0.50), P = 0.001]. However, there was no significant difference in terms of the laser time, duration of hospital stay, drop of hemoglobin level, total energy, postoperative ureteral stenting, the incidence of intraoperative complications or postoperative complications between TFL and Ho: YAGs. CONCLUSION: The findings of this study demonstrated several advantages of TFL in terms of higher SFR, shorter operative time and less stone migration. TRIAL REGISTRATION: The protocol of this systematic review was listed in PROSPERO ( www.crd.york.ac.uk/PROSPERO ) (Protocol number: CRD42022362550).

A review of methods for assessment of cognitive function in high-altitude hypoxic environments.

Hypoxic environments like those present at high altitudes may negatively affect brain function. Varying levels of hypoxia, whether acute or chronic, are previously shown to impair cognitive function in humans. Assessment and prevention of such cognitive impairment require detection of cognitive changes and impairment using specific cognitive function assessment tools. This paper summarizes the findings of previous research, outlines the methods for cognitive function assessment used at a high altitude, elaborates the need to develop standardized and systematic cognitive function assessment tools for high-altitude hypoxia environments.

RIRS with FV-UAS vs. MPCNL for 2-3-cm upper urinary tract stones: a prospective study.

To observe the efficacy and safety of retrograde intrarenal surgery (RIRS) combined with flexible vacuum-assisted ureteral access sheath (FV-UAS) and minimally invasive percutaneous nephrolithotomy (MPCNL) in patients with 2-3 cm upper urinary tract stones. A total of 160 patients with 2-3 cm upper urinary tract stones were prospectively randomized into 2 groups-80 in the FV-UAS group and 80 cases as control in the MPCNL group. The stone-free rates (SFRs) at different times (postoperative 1st day and 4th week) were considered as the primary outcome of the study. The secondary end points were operative time, hemoglobin decrease, postoperative hospital stay, and operation-related complications. There was no obvious difference between the two groups in patient's demographics and preoperative clinical characteristics (all P > 0.05). Postoperative data showed that mean decrease in hemoglobin level was less in FV-UAS group than that in MPCNL group (5.3 vs. 10.8 g/L, P < 0.001). Postoperative hospital stay in FV-UAS group was more shorten than that in MPCNL group (2.7 vs. 4.9 days, P < 0.001). There was no statistical significance between the two groups in SFRs during postoperative 1st day and 4th week (both P > 0.05). However, in terms of the rates of bleeding and pain, MPCNL group were both significantly higher than FV-UAS group (6.2 vs. 0.0%, P = 0.023; 16.2 vs. 2.5%, P = 0.003; respectively). Our study showed that RIRS with FV-UAS, a new partnership to treat 2-3 cm upper urinary tract stones, was satisfying as it achieved a high SFR rate and a low rate of complications. This method was safe and reproducible in clinical practice.

RNA binding protein PUM2 promotes IL-1ß-induced apoptosis of chondrocytes via regulating FOXO3 expression.

Objective: RNA-binding proteins (RBPs) have been recently proven to be involved in the pathogenesis of several diseases. However, few studies elaborated RBPs in regulating osteoarthritis. This study aims to define the function and mechanism of RBPs-PUM2 in chondrocyte apoptosis during osteoarthritis. Methods: Cartilage tissue samples and human juvenile chondrocyte cell line C28/I2 were collected for further study. PUM2 expression in the human tissues and cells was determined using qRT-PCR. Chondrocyte viability and apoptosis were determined by MTT and flow cytometry. ROS generation was determined by flow cytometry. The regulation of PUM2 on FOXO3 translation was evaluated by RNA immunoprecipitation, RNA pull-down, and Luciferase gene reporter analysis. Results: PUM2 is upregulated in both cartilage tissue of osteoarthritis patients and IL-1ß-stimulated chondrocytes. PUM2 overexpression reduces cell viability and promotes cell apoptosis and ROS generation of chondrocytes. PUM2 silencing increases cell viability and ameliorates cell apoptosis as well as ROS generation in chondrocytes induced by IL-1ß. PUM2 inhibits FOXO3 expression via binding its mRNA 3'-UTR. PUM2 forms a signaling axis with FOXO3 in IL-1ß induced chondrocyte damage. Conclusion: PUM2 is upregulated in cartilage tissue of osteoarthritis and positively regulates chondrocytes apoptosis through controlling FOXO3 protein expression.

Enhanced bone regeneration via endochondral ossification using Exendin-4-modified mesenchymal stem cells.

Nonunions and delayed unions pose significant challenges in orthopedic treatment, with current therapies often proving inadequate. Bone tissue engineering (BTE), particularly through endochondral ossification (ECO), emerges as a promising strategy for addressing critical bone defects. This study introduces mesenchymal stem cells overexpressing Exendin-4 (MSC-E4), designed to modulate bone remodeling via their autocrine and paracrine functions. We established a type I collagen (Col-I) sponge-based in vitro model that effectively recapitulates the ECO pathway. MSC-E4 demonstrated superior chondrogenic and hypertrophic differentiation and enhanced the ECO cell fate in single-cell sequencing analysis. Furthermore, MSC-E4 encapsulated in microscaffold, effectively facilitated bone regeneration in a rat calvarial defect model, underscoring its potential as a therapeutic agent for bone regeneration. Our findings advocate for MSC-E4 within a BTE framework as a novel and potent approach for treating significant bone defects, leveraging the intrinsic ECO process.

Gas chromatography ion mobility spectroscopy: A rapid and effective tool for monitoring oil oxidation.

Oil autoxidation is an early process of food deterioration, monitoring oil oxidation is therefore of great significance to ensure food quality and safety. In this study, a detection method of the primary and secondary oxidative products was developed by gas chromatography ion mobility spectrometry (GC-IMS).The secondary oxidative products was analyzed by GC-IMS. Then, the relationships between peroxide values and the contents of secondary oxidative products were investigated by constructing a prediction model of peroxide value of rapeseed oil with the help of secondary oxidative products and chemometrics. The coefficient of determination Q2 of the model validation set is 0.96, and the RMSECV is 0.1570 g/100 g. These validation results indicated that secondary oxidative products could also reflect the content of the primary oxidative products. Moreover, 10 characteristic markers related to oxidative rancidity were identified for monitoring edible oil rancidity and oxidative stability.

Using A Google Web Search Analysis to Assess the Utility of ChatGPT in Stem Cell Therapy.

OBJECTIVE: Since its introduction, the use of ChatGPT has increased significantly for medically related purposes. However, current research has not captured its applications in providing information on stem cell therapy. To address this gap, the present study compared the effectiveness of ChatGPT to Google in answering medical questions related to stem cell therapy. METHODS: The search term "stem cell therapy" was used to perform a Google web search, and the top 20 frequently asked questions along with answers were recorded together with relevant website sources. Of these questions, the top 10 questions were separately entered into ChatGPT, and the answers and the sources were recorded. Then, the following statement was entered into ChatGPT: "Do a Google search with the search term 'stem cell therapy' and record 20 common questions related to the search term." After obtaining these questions, each question was separately entered into ChatGPT for an answer and source. RESULTS: A majority of the top 20 questions provided by Google were related to fact, whereas a majority of the questions provided by ChatGPT were related to policy. The answer sources used by Google were mostly drawn from medical practice, while those used by ChatGPT were mostly drawn from academic information. CONCLUSION: Compared to Google, ChatGPT exhibits stronger capabilities in promoting awareness of stem cell therapy. ChatGPT has the ability to eliminate misleading information by providing accurate and reliable answers. However, the responses provided by ChatGPT are still general in nature and cannot substitute academic sources for providing specialized knowledge.

Incidence and trends of type 1 diabetes before and after 2000 in the Western Pacific Region: A systematic review and meta-analysis.

OBJECTIVES: To undertake a systematic review of publications describing Type 1 diabetes (T1DM) incidence, trends over time and associated factors in the Western Pacific Region (WPR). METHODS: As per the PROSPERO-registered (CRD42019122646) protocol English (MEDLINE, Embase, Global Health) and Chinese data-bases (China National Knowledge Infrastructure, VIP, Wanfang) from onset to 31/12/2019 were searched for T1DM incidence in the WPR. Country level data extracted included annual crude incidence rates by sex, number of new cases per annum (p.a.) and cumulatively, and the population at-risk. A meta-analysis for T1DM incidence was performed (by region and narrow age-bands, where possible) with subgroup analyses by time and by region. FINDINGS: Forty-five population-based studies (21 from China), published 1973-2017, estimated T1DM incidence, mostly in youth, in 11 WPR countries. After 2000, mean annual T1DM incidence/100,000 person years aged 0-14 years ranged from 0.9 (95 % confidence intervals (CI), 0.6-1.3) in Fiji to 23.2 (95 % CI, 21.3-25.2) in Australia. The mean annual increase over time ranged from 2.8 % in Australia (1990-2002) to 14.2 % in Shanghai (1997-2011). T1DM incidence increased most in China (2.7-fold over 30-years) then Thailand (2-fold over 15-years). Most studies documented increasing incidence with age, though only two studies included people aged ≥ 20 years. Many, but not all studies reported significantly higher T1DM incidence in females vs. males. CONCLUSION: T1DM incidence in the WPR is generally increasing, varying by age, sex, time and country. Results increase understanding of regional T1DM incidence and inform research and healthcare strategies.

Quercetin is a Potential Therapy for Rheumatoid Arthritis via Targeting Caspase-8 Through Ferroptosis and Pyroptosis.

Background: Rheumatoid arthritis (RA) is one of the most common chronic inflammatory autoimmune diseases. However, the underlying molecular mechanisms of its pathogenesis are unknown. This study aimed to identify the common biomarkers of ferroptosis and pyroptosis in RA and screen potential drugs. Methods: The RA-related differentially expressed genes (DEGs) in GSE55235 were screened by R software and intersected with ferroptosis and pyroptosis gene libraries to obtain differentially expressed ferroptosis-related genes (DEFRGs) and differentially expressed pyroptosis-related genes (DEPRGs). We performed Gene Ontology (GO), Kyoto Encyclopedia of the Genome (KEGG), ClueGO, and Protein-Protein Interaction (PPI) analysis for DEFRGs and DEPRGs and validated them by machine learning. The microRNA/transcription factor (TF)-hub genes regulatory network was further constructed. The key gene was validated using the GSE77298 validation set, cellular validation was performed in in vitro experiments, and immune infiltration analysis was performed using CIBERSORT. Network pharmacology was used to find key gene-targeting drugs, followed by molecular docking and molecular dynamics simulations to analyze the binding stability between small-molecule drugs and large-molecule proteins. Results: Three hub genes (CASP8, PTGS2, and JUN) were screened via bioinformatics, and the key gene (CASP8) was validated and obtained through the validation set, and the diagnostic efficacy was verified to be excellent through the receiver operating characteristic (ROC) curves. The ferroptosis and pyroptosis phenotypes were constructed by fibroblast-like synoviocytes (FLS), and caspase-8 was detected and validated as a common biomarker for ferroptosis and pyroptosis in RA, and quercetin can reduce caspase-8 levels. Quercetin was found to be a potential target drug for caspase-8 by network pharmacology, and the stability of their binding was further verified using molecular docking and molecular dynamics simulations. Conclusion: Caspase-8 is an important biomarker for ferroptosis and pyroptosis in RA, and quercetin is a potential therapy for RA via targeting caspase-8 through ferroptosis and pyroptosis.

Intelligent Electrochemical Point-of-Care Test Method with Interface Control Based on DNA Pyramids: Aflatoxin B1 Detection in Food and the Environment.

Sensitive, intelligent point-of-care test (iPOCT) methods for small molecules like aflatoxin B1 (AFB1) are urgently needed for food and the environment. The challenge remains of surface control in iPOCT. Herein, we developed an electrochemical sensor based on the DNA pyramid (DNP), combining a smartphone, app, and mobile electrochemical workstations to detect AFB1. The DNP's structure can reduce local overcrowding and entanglement between neighboring probes, control the density and orientation of recognition probes (antibodies), produce uniform and orientational surface assemblies, and improve antigen-antibody-specific recognition and binding efficiency. Simultaneously, the hollow structure of the DNP enhances the electron transfer capacity and increases the sensitivity of electrochemical detection. In this work, the biosensor based on DNP was first combined with electrochemical (Ec) iPOCT to simultaneously achieve ordered interface modulation of recognition probes and intelligent detection of AFB1. Under optimal conditions, we found a detection limit of 3 pg/mL and a linear range of 0.006-30 ng/mL (R2 = 0.995). Further, using peanut, soybean, corn, and lake water as complex matrices, it recorded recoveries of 82.15-100.53%, excellent selectivity, acceptable stability, and good reproducibility. Finally, this Ec iPOCT provides consistent results compared to the high-performance liquid chromatography-tandem mass spectrometry method.

Mendelian randomization analysis suggests no associations of human herpes viruses with amyotrophic lateral sclerosis.

Background: The causal associations between infections with human herpes viruses (HHVs) and amyotrophic lateral sclerosis (ALS) has been disputed. This study investigated the causal associations between herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), HHV-6, and HHV-7 infections and ALS through a bidirectional Mendelian randomization (MR) method. Methods: The genome-wide association studies (GWAS) database were analyzed by inverse variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode methods. MR-Egger intercept test, MR-PRESSO test, Cochran's Q test, funnel plots, and leaveone-out analysis were used to verify the validity and robustness of the MR results. Results: In the forward MR analysis of the IVW, genetically predicted HSV infections [odds ratio (OR) = 0.9917; 95% confidence interval (CI): 0.9685-1.0154; p = 0.4886], HSV keratitis and keratoconjunctivitis (OR = 0.9897; 95% CI: 0.9739-1.0059; p = 0.2107), anogenital HSV infection (OR = 1.0062; 95% CI: 0.9826-1.0304; p = 0.6081), VZV IgG (OR = 1.0003; 95% CI: 0.9849-1.0160; p = 0.9659), EBV IgG (OR = 0.9509; 95% CI: 0.8879-1.0183; p = 0.1497), CMV (OR = 0.9481; 95% CI: 0.8680-1.0357; p = 0.2374), HHV-6 IgG (OR = 0.9884; 95% CI: 0.9486-1.0298; p = 0.5765) and HHV-7 IgG (OR = 0.9991; 95% CI: 0.9693-1.0299; p = 0.9557) were not causally associated with ALS. The reverse MR analysis of the IVW revealed comparable findings, indicating no link between HHVs infections and ALS. The reliability and validity of the findings were verified by the sensitivity analysis. Conclusion: According to the MR study, there is no evidence of causal associations between genetically predicted HHVs (HSV, VZV, EBV, CMV, HHV-6, and HHV-7) and ALS.

An orientation-free ring feature descriptor with stain-variability normalization for pathology image matching.

Comprehensively analyzing the corresponding regions in the images of serial slices stained using different methods is a common but important operation in pathological diagnosis. To help increase the efficiency of the analysis, various image registration methods are proposed to match the corresponding regions in different images, but their performance is highly influenced by the rotations, deformations, and variations of staining between the serial pathology images. In this work, we propose an orientation-free ring feature descriptor with stain-variability normalization for pathology image matching. Specifically, we normalize image staining to similar levels to minimize the impact of staining differences on pathology image matching. To overcome the rotation and deformation issues, we propose a rotation-invariance orientation-free ring feature descriptor that generates novel adaptive bins from ring features to build feature vectors. We measure the Euclidean distance of the feature vectors to evaluate keypoint similarity to achieve pathology image matching. A total of 46 pairs of clinical pathology images in hematoxylin-eosin and immunohistochemistry straining to verify the performance of our method. Experimental results indicate that our method meets the pathology image matching accuracy requirements (error ¡ 300µm), especially competent for large-angle rotation cases common in clinical practice.

Changes of health-related quality of life after initiating basal insulin treatment among people with type 2 diabetes.

To assess the association between insulin regimens and health-related quality of life (HRQoL) after the introduction of basal insulin (BI) among people with type 2 diabetes in real-world clinical settings. 16,339 registered people with diabetes who had inadequate glycaemic control by oral agents initiated BI (either single BI or Basal-bolus) and completed a 6-month follow-up from 209 hospitals were included in the analyses. At the end of the follow-up, the switches of insulin regimens, change of HRQoL (EQ-5D-3L) and their associations were assessed. Initial insulin regimens of single BI and of basal-bolus (BI included Glargine, Detemir, and Neutral Protamine Hagedorn) accounted for 75.6% and 24.4%, respectively. At 6 months, regimens used were BI alone (65.2%), basal-bolus (10.4%), and premixed (6.4%), whereas 17.9% stopped all insulin therapy. The visual analogue scale score increased by 5.46 (P < .001), and the index value increased slightly by 0.02 (P < .001). Univariate analysis showed that people with diabetes taking basal-bolus regimen had the greatest improvement on HRQoL in all dimensions, especially in the reduction of the percentage of Pain/Discomfort (by 10.03%) and Anxiety/Depression (by 11.21%). In multivariable analysis, single BI or premixed insulin at 6 months was associated with more improvement of visual analogue scale score compared with stopping all insulin. Improved HRQoL was observed after initiating BI in people with type 2 diabetes . If the same achievement on HbA1c control can be guaranteed, single BI is preferred to other regimens from the viewpoint of HRQoL. Basal-bolus has the most significant potential to increase HRQoL, however, the people with diabetes characteristics differ from those initiating BI alone. Further longitudinal cohort study with a longer study period might be necessary to evaluate the certain effect.