Comparison of Statin With Ezetimibe Combination Therapy Versus Statin Monotherapy for Primary Prevention in Middle-Aged Adults.

BACKGROUND AND OBJECTIVES: Lipid lowering therapy is essential to reduce the risk of major cardiovascular events; however, limited evidence exists regarding the use of statin with ezetimibe as primary prevention strategy for middle-aged adults. We aimed to investigate the impact of single pill combination therapy on clinical outcomes in relatively healthy middle-aged patients when compared with statin monotherapy. METHODS: Using the Korean National Health Insurance Service database, a propensity score match analysis was performed for baseline characteristics of 92,156 patients categorized into combination therapy (n=46,078) and statin monotherapy (n=46,078) groups. Primary outcome was composite outcomes, including death, coronary artery disease, and ischemic stroke. And secondary outcome was all-cause death. The mean follow-up duration was 2.9±0.3 years. RESULTS: The 3-year composite outcomes of all-cause death, coronary artery disease, and ischemic stroke demonstrated no significant difference between the 2 groups (10.3% vs. 10.1%; hazard ratio (HR), 1.022; 95% confidence interval [CI], 0.980-1.064; p=0.309). Meanwhile, the 3-year all-cause death rate was lower in the combination therapy group than in the statin monotherapy group (0.2% vs. 0.4%; p<0.001), with a significant HR of 0.595 (95% CI, 0.460-0.769; p<0.001). Single pill combination therapy exhibited consistently lower mortality rates across various subgroups. CONCLUSIONS: Compared to the statin monotherapy, the combination therapy for primary prevention showed no difference in composite outcomes but may reduce mortality risk in relatively healthy middle-aged patients. However, since the study was observational, further randomized clinical trials are needed to confirm these findings.

Comparing underwater endoscopic submucosal dissection and conventional endoscopic submucosal dissection for large laterally spreading tumor: a randomized controlled trial.

BACKGROUND AND AIMS: Colorectal endoscopic submucosal dissection (ESD) is challenging despite its usefulness. Underwater ESD (UESD) provides better traction and a clearer view of the submucosal layer than conventional ESD (CESD). This study compared the efficiency of UESD and CESD for large (20-50 mm) laterally spreading tumor (LST). METHODS: Preplanned sample size was calculated from our previous experience. As a results, 28 patients were required to UESD group or CESD group, respectively. The primary outcome was total procedure time while the secondary outcome was dissection speed. RESULTS: Fifty-six patients were enrolled and a total of 28 patients were assigned to each group. The mean size of LST was 31.6 mm and 31.3 mm in the UESD and CESD group, respectively. Fibrosis was observed in 67.9% and 60.7% patients in the UESD and CESD group. Total procedure time (mean [SD]) for the UESD group was significantly shorter than that for the CESD group, respectively (49.5 minutes [20.3] vs 75.7 minutes [36.1]; mean difference, -26.2 minutes; 95% CI, -42.0 to -10.5). Dissection speed of the UESD group was significantly faster than that of the CESD group (21.9 mm2/min [6.9] vs 15.2 mm2/min [7.3]; mean difference, 6.7 mm2/minutes; 95% CI, 2.8-10.4). There was no difference between groups in the R0 resection rate or en bloc resection rate. No perforations were observed in either group. CONCLUSIONS: UESD was superior to CESD in total procedure time and dissection speed. UESD can be recommended as the preferred method for the resection of large LST.

Intravascular ultrasound-guided drug-coated balloon angioplasty for femoropopliteal artery disease: a clinical trial.

BACKGROUND AND AIMS: Drug-coated balloons (DCBs) have demonstrated favourable outcomes following endovascular therapy for femoropopliteal artery (FPA) disease. However, uncertainty remains whether the use of intravascular ultrasound (IVUS) can improve the outcomes of DCBs. METHODS: This prospective, multicentre, randomized trial, conducted at seven centres in South Korea, compared the outcomes of IVUS-guided vs. angiography-guided angioplasty for treating FPA disease with DCBs. Patients were assigned to receive IVUS-guided (n = 119) or angiography-guided (n = 118) angioplasty using DCBs. The primary endpoint was 12-month primary patency. RESULTS: Between May 2016 and August 2022, 237 patients were enrolled and 204 (86.0%) completed the trial (median follow-up; 363 days). The IVUS guidance group showed significantly higher primary patency [83.8% vs. 70.1%; cumulative difference 19.6% (95% confidence interval 6.8 to 32.3); P = .01] and increased freedom from clinically driven target lesion revascularization [92.4% vs. 83.0%; difference 11.6% (95% confidence interval 3.1 to 20.1); P = .02], sustained clinical improvement (89.1% vs. 76.3%, P = .01), and haemodynamic improvement (82.4% vs. 66.9%, P = .01) at 12 months compared with the angiography guidance group. The IVUS group utilized larger balloon diameters and pressures for pre-dilation, more frequent post-dilation, and higher pressures for post-dilation, resulting in a greater post-procedural minimum lumen diameter (3.90 ± 0.59 vs. 3.71 ± 0.73 mm, P = .03). CONCLUSIONS: Intravascular ultrasound guidance significantly improved the outcomes of DCBs for FPA disease in terms of primary patency, freedom from clinically driven target lesion revascularization, and sustained clinical and haemodynamic improvement at 12 months. These benefits may be attributed to IVUS-guided optimization of the lesion before and after DCB treatment.

Stem Cell-Derived Extracellular Vesicle-Bearing Injectable Hydrogel for Collagen Generation in Dermis.

Despite the remarkable advances of dermal fillers that reduce wrinkles caused by dermis thickness reduction, they still lack effective hydrogel systems that stimulate collagen generation along with injection convenience. Here, we develop a stem cell-derived extracellular vesicle (EV)-bearing thermosensitive hydrogel (EVTS-Gel) for effective in vivo collagen generation. The TS-Gel undergoes sol-gel transition at 32.6 °C, as demonstrated by the storage and loss moduli crossover. Moreover, the TS-Gel and the EVTS-Gel have comparable rheological properties. Both hydrogels are injected in a sol state; hence, they require lower injection forces than conventional hydrogel-based dermal fillers. When locally administered to mouse skin, the TS-Gel extends the retention time of EVs by 2.23 times. Based on the nature of the controlled EV release, the EVTS-Gel significantly inhibits the dermis thickness reduction caused by aging compared to the bare EV treatment for 24 weeks. After a single treatment, the collagen layer thickness of the EVTS-Gel-treated dermis becomes 2.64-fold thicker than that of the bare EV-treated dermis. Notably, the collagen generation efficacy of the bare EV is poorer than that of the EVTS-Gel of a 10× lesser dose. Overall, the EVTS-Gel shows potential as an antiaging dermal filler for in vivo collagen generation.

Glass transition temperature as a unified parameter to design self-healable elastomers.

Self-healing ability of materials, particularly polymers, improves their functional stabilities and lifespan. To date, the designs for self-healable polymers have relied on specific intermolecular interactions or chemistries. We report a design methodology for self-healable polymers based on glass transition. Statistical copolymer series of two monomers with different glass transition temperatures (Tg) were synthesized, and their self-healing tendency depends on the Tg of the copolymers and the constituents. Self-healing occurs more efficiently when the difference in Tg between two monomer units is larger, within a narrow Tg range of the copolymers, irrespective of their functional groups. The self-healable copolymers are elastomeric and nonpolar. The strategy to graft glass transition onto self-healing would expand the scope of polymer design.

Recombinant Human IL-32θ Induces Polarization Into M1-like Macrophage in Human Monocytic Cells.

The tumor microenvironment (TME) is formed by several immune cells. Notably, tumor-associated macrophages (TAMs) are existed in the TME that induce angiogenesis, metastasis, and proliferation of cancer cells. Recently, a point-mutated variant of IL-32θ was discovered in breast cancer tissues, which suppressed migration and proliferation through intracellular pathways. Although the relationship between cancer and IL-32 has been previously studied, the effects of IL-32θ on TAMs remain elusive. Recombinant human IL-32θ (rhIL-32θ) was generated using an Escherichia coli expression system. To induce M0 macrophage polarization, THP-1 cells were stimulated with PMA. After PMA treatment, the cells were cultured with IL-4 and IL-13, or rhIL-32θ. The mRNA level of M1 macrophage markers (IL-1ß, TNFα, inducible nitric oxide synthase) were increased by rhIL-32θ in M0 macrophages. On the other hand, the M2 macrophage markers (CCL17, CCL22, TGFß, CD206) were decreased by rhIL-32θ in M2 macrophages. rhIL-32θ induced nuclear translocation of the NF-κB via regulation of the MAPK (p38) pathway. In conclusion, point-mutated rhIL-32θ induced the polarization to M1-like macrophages through the MAPK (p38) and NF-κB (p65/p50) pathways.

Do toenail manganese and iron levels reflect brain metal levels or brain metabolism in welders?

Inhalation of welding fumes can cause metal accumulation in the brain, leading to Parkinsonian-like symptoms. Metal accumulation and altered neurochemical profiles have been observed using magnetic resonance imaging (MRI) in highly exposed welders, being associated with decreased motor function and cognition. While MRI is impractical to use as a health risk assessment tool in occupational settings, toenail metal levels are easier to assess and have been demonstrated to reflect an exposure window of7-12 months in the past. Yet, it is unclear whether toenail metal levels are associated with brain metal levels or changes in metabolism, which are the root of potential health concerns. This study investigates whether toenail manganese (Mn) and iron (Fe) levels, assessed at several time points, correlate with brain Mn and Fe levels, measured by MRI, as well as brain GABA, glutamate (Glu), and glutathione (GSH) levels, measured by Magnetic Resonance Spectroscopy (MRS), in seventeen Mn-exposed welders. Quantitative T1 and R2* MRI maps of the whole brain, along with GABA, Glu, and GSH MRS measurements from the thalamus and cerebellum were acquired at baseline (T0). Toenail clippings were collected at T0 and every three months after the MRI for a year to account for different exposure periods being reflected by toenail clippings and MRI. Spearman correlations of toenail metal levels were run against brain metal and metabolite levels, but no significant associations were found for Mn at any timepoint. Cerebellar GSH positively correlated with toenail Fe clipped twelve months after the MRI (p = 0.05), suggesting an association with Fe exposure at the time of the MRI. Neither thalamic GABA nor Glu correlated with toenail Fe levels. In conclusion, this study cannot support toenail Mn as a proxy for brain Mn levels or metabolic changes, while toenail Fe appears linked to brain metabolic alterations, underscoring the importance of considering other metals, including Fe, in studying Mn neurotoxicity.

A phase 3, randomized, double-blind, multicenter, placebo-controlled study of S-588410, a five-peptide cancer vaccine as an adjuvant therapy after curative resection in patients with esophageal squamous cell carcinoma.

BACKGROUND: S-588410, a cancer peptide vaccine (CPV), comprises five HLA-A*24:02-restricted peptides from five cancer-testis antigens. In a phase 2 study, S-588410 was well-tolerated and exhibited antitumor efficacy in patients with urothelial cancer. Therefore, we aimed to evaluate the efficacy, immune response, and safety of S-588410 in patients with completely resected esophageal squamous cell carcinoma (ESCC). METHODS: This phase 3 study involved patients with HLA-A*24:02-positive and lymph node metastasis-positive ESCC who received neoadjuvant therapy followed by curative resection. After randomization, patients were administered S-588410 and placebo (both emulsified with Montanide™ ISA 51VG) subcutaneously. The primary endpoint was relapse-free survival (RFS). The secondary endpoints were overall survival (OS), cytotoxic T-lymphocyte (CTL) induction, and safety. Statistical significance was tested using the one-sided weighted log-rank test with the Fleming-Harrington class of weights. RESULTS: A total of 276 patients were randomized (N = 138/group). The median RFS was 84.3 and 84.1 weeks in the S-588410 and placebo groups, respectively (P = 0.8156), whereas the median OS was 236.3 weeks and not reached, respectively (P = 0.6533). CTL induction was observed in 132/134 (98.5%) patients who received S-588410 within 12 weeks. Injection site reactions (137/140 patients [97.9%]) were the most frequent treatment-emergent adverse events in the S-588410 group. Prolonged survival was observed in S-588410-treated patients with upper thoracic ESCC, grade 3 injection-site reactions, or high CTL intensity. CONCLUSIONS: S-588410 induced immune response and had acceptable safety but failed to reach the primary endpoint. A high CTL induction rate and intensity may be critical for prolonging survival during future CPV development.

Unraveling the Photovoltage Formation Mechanism in Indium-Tin Oxide Branched Nanowires/Poly(3-Hexylthiophene) Photorechargeable Supercapacitors.

Photorechargeable supercapacitors are promising next-generation renewable energy storage devices. Previously, a hybrid structure consisting of indium-tin oxide branched nanowires (ITO BRs) and poly(3-hexylthiophene) (P3HT) was demonstrated as a photorechargeable supercapacitor. However, the formation mechanism of photovoltage has not been studied. Herein, we experimentally investigated the photovoltage-determining parameters in the ITO BRs/P3HT photorechargeable supercapacitor by inserting a polyethylenimine ethoxylated (PEIE) interlayer or adding a phenyl-C61-butyric acid methyl ester (PCBM) electron acceptor. Coating the PEIE interlayer on ITO BRs decreased the work function by 0.5 eV and hindered the hole extraction from P3HT to ITO BRs, leading to interfacial recombination and a decrease in photovoltage. On the other hand, the addition of PCBM promoted the charge transfer of the electrons from P3HT to PCBM, enhanced the redox reaction at the PCBM/electrolyte interface, and reduced the number of accumulated electrons, leading to a decreased photovoltage. From these results, we found that two key parameters determine the photovoltage and charge storage capability; one is the interfacial recombination at the ITO BRs/P3HT interface and the other is the redox reaction at the P3HT/electrolyte interface.

Calibrated CAR Signaling Enables Low-Dose Therapy in Large B-Cell Lymphoma.

We designed a CD19-targeted CAR comprising a calibrated signaling module, termed 1XX, that differs from that of conventional CD28/CD3z and 4-1BB/CD3z CARs. Here we report the first-in-human, phase 1 clinical trial of 19(T2)28z-1XX CAR T cells in relapsed/refractory large B-cell lymphoma. We hypothesized that 1XX CAR T cells may be effective at low doses and investigated 4 doubling dose levels starting from 25×106 CAR T cells. The overall response rate (ORR) was 82% and complete response (CR) rate 71% in the entire cohort (n=28) and 88% ORR and 75% CR in 16 patients treated at 25×106. With the median follow-up of 24 months, the 1-year EFS was 61% (95% CI: 45-82%). Overall, grade ≥3 CRS and ICANS rates were low at 4% and 7%. The calibrated potency of the 1XX CAR affords excellent efficacy at low cell doses and may benefit the treatment of other hematological malignancies, solid tumors and autoimmunity.

Clinicomicrobiological risk factors for infective endocarditis in viridans group streptococci bacteraemia.

BACKGROUND: When to perform echocardiography to rule out infective endocarditis (IE) in patients with viridans group streptococci (VGS) bloodstream infections (BSIs) is unclear. OBJECTIVES: We aimed to identify independent risk factors for IE in patients with VGS BSI. METHODS: This retrospective study conducted at Seoul National University Hospital from January 2013 to December 2022 involved patients with VGS and nutritionally variant streptococcal BSI, excluding single positive blood cultures and polymicrobial BSI cases. Independent risk factors were identified by multivariate logistic regression and sensitivity analyses according to echocardiography results, VGS species or the inclusion of possible IE cases. RESULTS: Of 845 VGS BSI cases, 349 were analysed and 86 IE cases were identified (24.6%). In the multivariate analysis, heart valve disease [adjusted odds ratio (aOR), 14.14, 95% CI, 6.14-32.58; P < 0.001], persistent bacteraemia (aOR, 5.12, 95% CI, 2.03-12.94; P = 0.001), age (per year, aOR, 0.98; 95% CI, 0.96-1.00; P = 0.015), solid cancer (aOR, 0.26; 95% CI, 0.13-0.53; P < 0.001) and haematologic malignancy (aOR, 0.04; 95% CI, 0.01-0.41; P = 0.006) were independently associated with IE. Sensitivity analyses yielded consistent results; also, infection by a member of the mitis group was independent risk factor for IE (aOR, 6.50; 95% CI, 2.87-14.68; P < 0.001). CONCLUSIONS: Younger age, heart valve disease, persistent bacteraemia, absence of underlying malignancy and BSI by a member of the mitis group were independent risk factors for IE in patients with VGS BSI. Echocardiographic evaluation could be prudently considered based on these clinicomicrobiological risk factors.

Sucralose Influences the Productive Performance, Carcass Traits, Blood Components, and Gut Microflora Using 16S rRNA Sequencing of Growing APRI-Line Rabbits.

This study investigated how sucralose influenced rabbit intestine and caecal microbial activity, blood parameters, growth performance, carcass characteristics, and digestibility. In total, 160 5-week-old rabbits from the APRI line weighing 563.29 gm were randomly assigned to four experimental groups with four replicates-5 males and 5 females in each. Four experimental groups were used, as follows: SUC1, SUC2, and SUC3 got 75, 150, and 300 mg of sucralose/kg body weight in water daily, while the control group ate a basal diet without supplements. The results showed that both the control and SUC1 groups significantly (p < 0.05) increased daily weight gain and final body weight. Sucralose addition significantly improved feed conversion ratio (p < 0.05) and decreased daily feed intake (gm/d). The experimental groups do not significantly differ in terms of mortality. Furthermore, nutrient digestibility was not significantly affected by sucralose treatment, with the exception of crud protein digestion, which was significantly reduced (p < 0.05). Additionally, without altering liver or kidney function, sucralose administration dramatically (p < 0.05) decreased blood serum glucose and triglyceride levels while increasing total lipids, cholesterol, and malonaldehyde in comparison to the control group. Furthermore, the addition of sucrose resulted in a significant (p < 0.05) increase in the count of total bacteria, lactobacillus, and Clostridium spp., and a decrease in the count of Escherichia coli. Further analysis using 16S rRNA data revealed that sucralose upregulated the expression of lactobacillus genes but not that of Clostridium or E. Coli bacteria (p < 0.05). Therefore, it could be concluded that sucralose supplementation for rabbits modifies gut microbiota and boosts beneficial bacteria and feed conversion ratios without side effects. Moreover, sucralose could decrease blood glucose and intensify hypercholesterolemia and should be used with caution for human consumption.

Development and validation of risk prediction model for post-donation renal function in living kidney donors.

This study aimed to create and validate a predictive model for renal function following live kidney donation, using pre-donation factors. Accurately predicting remaining renal function post live kidney donation is currently insufficient, necessitating an effective assessment tool. A multicenter retrospective study of 2318 live kidney donors from two independent centers (May 2007-December 2019) was conducted. The primary endpoint was the reduction in eGFR to below 60 mL/min/m2 6 months post-donation. The primary endpoint was achieved in 14.4% of the training cohort and 25.8% of the validation cohort. Sex, age, BMI, hypertension, preoperative eGFR, and remnant kidney proportion (RKP) measured by computerized tomography (CT) volumetry were found significant in the univariable analysis. These variables informed a scoring system based on multivariable analysis: sex (male: 1, female: 0), age at operation (< 30: 0, 30-39: 1, 40-59: 2, ≥ 60: 3), preoperative eGFR (≥ 100: 0, 90-99: 2, 80-89: 4, < 80: 5), and RKP (≥ 52%: 0, < 52%: 1). The total score ranged from 0 to 10. The model showed good discrimination for the primary endpoint in both cohorts. The prediction model provides a useful tool for estimating post-donation renal dysfunction risk, factoring in the side of the donated kidney. It offers potential enhancement to pre-donation evaluations.

Tenovin-1, a Selective SIRT1/2 Inhibitor, Attenuates High-fat Diet-induced Hepatic Fibrosis via Inhibition of HSC Activation in ZDF Rats.

Type 2 diabetes mellitus (T2DM) increases the risk of non-alcoholic fatty liver disease (NAFLD) progression to advanced stages, especially upon high-fat diet (HFD). HFD-induced hepatic fibrosis can be marked by oxidative stress, inflammation, and activation of hepatic stellate cells. Sirtuin 1/2 (SIRT1/2), NAD-dependent class III histone deacetylases, are involved in attenuation of fibrosis. In our conducted research, TGF-ß1-activated LX-2 cells, free fatty acid (FFA)-treated simultaneous co-culture (SCC) cells, and HFD-induced hepatic fibrosis in Zucker diabetic fatty (ZDF) rats, a widely used animal model in the study of metabolic syndromes, were used to evaluate the protective effect of Tenovin-1, a SIRT1/2 inhibitor. ZDF rats were divided into chow diet, HFD, and HFD + Tenovin-1 groups. Tenovin-1 reduced hepatic damage, inhibited inflammatory cell infiltration, micro/ macro-vesicular steatosis and prevented collagen deposition HFD-fed rats. Tenovin-1 reduced serum biochemical parameters, triglyceride (TG) and malondialdehyde (MDA) levels but increased glutathione, catalase, and superoxide dismutase levels. Tenovin-1 mitigated proinflammatory cytokines IL-6, IL-1ß, TNFα and fibrosis biomarkers in HFD rats, TGF-ß1-activated LX-2 and FFA treated SCC cells. Additionally, Tenovin-1 suppressed SIRT1/2 expression and inhibited JNK-1 and STAT3 phosphorylation in HFD rats and FFA-treated SCC cells. In conclusion, Tenovin-1 attenuates hepatic fibrosis by stimulating antioxidants and inhibiting inflammatory cytokines under HFD conditions in diabetic rats.

Subsequent Malignancies After CD19-Targeted Chimeric Antigen Receptor T Cells in Patients With Lymphoma.

Chimeric antigen receptor (CAR) T cells are an established treatment for B cell non-Hodgkin lymphomas (B-NHL). With the remarkable success in improving survival, understanding the late effects of CAR T cell therapy is becoming more relevant. The aim of this study is to determine the incidence of subsequent malignancies in adult patients with B-NHL. We retrospectively studied 355 patients from 2 different medical centers treated with four different CAR T cell products from 2016 to 2022. The overall cumulative incidence for subsequent malignancies at 36 months was 14% (95% CI: 9.2%, 19%). Subsequent malignancies were grouped into 3 primary categories: solid tumor, hematologic malignancy, and dermatologic malignancy with cumulative incidences at 36 months of 6.1% (95% CI: 3.1%-10%), 4.5% (95% CI: 2.1%-8.1%) and 4.2% (95% CI: 2.1%-7.5%) respectively. Notably, no cases of T cell malignancies were observed. In univariable analysis, increasing age was associated with higher risk for subsequent malignancy. While the overall benefits of CAR T products continue to outweigh their potential risks, more studies and longer follow ups are needed to further demonstrate the risks, patterns, and molecular pathways that lead to the development of subsequent malignancies.

PIEZO1 activation may serve as an early tissue biomarker for the prediction of irradiation-induced salivary gland dysfunction.

Irradiation (IR)-induced xerostomia is the most common side effect of radiation therapy in patients with head and neck cancer (HNC). Xerostomia diagnosis is mainly based on the patient's medical history and symptoms. Currently, no direct biomarkers are available for the early prediction of IR-induced xerostomia. Here, we identified PIEZO1 as a novel predictive tissue biomarker for xerostomia. Our data demonstrate that PIEZO1 is significantly upregulated at the gene and protein levels during IR-induced salivary gland (SG) hypofunction. Notably, PIEZO1 upregulation coincided with that of inflammatory (F4/80) and fibrotic markers (fibronectin and collagen fibers accumulation). These findings suggest that PIEZO1 upregulation in SG tissue may serve as a novel predictive marker for IR-induced xerostomia.

Modified Thoracoabdominal Nerves Block Through Perichondral Approach: A Systematic Review and Meta-analysis.

PURPOSE: This systematic review and meta-analysis aimed to investigate the postoperative analgesic efficacy and safety of the modified thoracoabdominal nerve block through the perichondral approach (M-TAPA) in abdominal surgeries. DESIGN: Systematic review and meta-analysis. METHODS: We searched electronic databases to identify relevant studies comparing M-TAPA with conventional analgesic techniques. The primary outcome was the requirement for rescue analgesia at 12 and 24 hours postsurgery. Secondary outcomes included the 11-point numerical rating scale pain scores at 0, 1, 2, 4, 6, 8, 12, and 24 hours following surgery, global quality of recovery scores, and postoperative adverse events. FINDINGS: Five randomized controlled trials involving 308 patients were analyzed. M-TAPA showed no significant difference in the requirement for rescue analgesia at 12 hours (relative risk [RR]: 0.87; 95% confidence interval [CI]: 0.62, 1.22; P = .424; I2 = 40.7%; Ph = .185) and 24 hours (RR: 0.67; 95% CI: 0.22, 1.99; P = .252; I2 = 90.3%; Ph < .001) postsurgery compared to non-M-TAPA. No significant differences in numerical rating scale pain scores or global quality of recovery scores were found between the two groups (all P < .05). However, M-TAPA was associated with a lower occurrence of nausea (RR: 0.37; 95% CI: 0.22, 0.68; P < .001; I2 = 0%; Ph = .834), vomiting (RR: 0.32; 95% CI: 0.17, 0.62; P < .001; I2 = 0%; Ph = .884), and itching (RR: 0.38; 95% CI: 0.21, 0.70; P = .002; I2 = 0%; Ph = .826). CONCLUSIONS: There was no significant difference in analgesic efficacy and safety between M-TAPA and non-M-TAPA techniques.

Determining arsenic stress tolerance genes in rice (Oryza sativa L.) via genomic insights and QTL mapping with double haploid lines.

Arsenic, a hazardous heavy metal with potent carcinogenic properties, significantly affects key rice-producing regions worldwide. In this study, we present a quantitative trait locus (QTL) mapping investigation designed to identify candidate genes responsible for conferring tolerance to arsenic toxicity in rice (Oryza sativa L.) during the seedling stage. This study identified 17 QTLs on different chromosomes, including qCHC-1 and qCHC-3 on chromosome 1 and 3 related to chlorophyll content and qRFW-12 on chromosome 12 related to root fresh weight. Gene expression analysis revealed eight candidate genes exhibited significant upregulation in the resistant lines, OsGRL1, OsDjB1, OsZIP2, OsMATE12, OsTRX29, OsMADS33, OsABCG29, and OsENODL24. These genes display sequence alignment and phylogenetic tree similarities with other species and engaging in protein-protein interactions with significant proteins. Advanced gene-editing techniques such as CRISPR-Cas9 to precisely target and modify the candidate genes responsible for arsenic tolerance will be explore. This approach may expedite the development of arsenic-resistant rice cultivars, which are essential for ensuring food security in regions affected by arsenic-contaminated soil and water.

Real-time application of ITS and D1-D3 nanopore amplicon metagenomic sequencing in fungal infections: Enhancing fungal infection diagnostics.

While fungal infections cause considerable morbidity and mortality, the performance of the current diagnostic tests for fungal infection is low. Even though fungal metagenomics or targeted next-generation sequencing have been investigated for various clinical samples, the real-time clinical utility of these methods still needs to be elucidated. In this study, we used internal transcribed spacer (ITS) and D1-D3 ribosomal DNA nanopore amplicon metagenomic sequencing to assess its utility in patients with fungal infections. Eighty-four samples from seventy-three patients were included and categorized into 'Fungal infection,' 'Fungal colonization,' and 'Fungal contamination' groups based on the judgement of infectious disease specialists. In the 'Fungal infection' group, forty-seven initial samples were obtained from forty-seven patients. Three fungal cases detected not by the sequencing but by conventional fungal assays were excluded from the analysis. In the remaining cases, the conventional fungal assay-negative/sequencing-positive group (n=11) and conventional fungal assay-positive/sequencing-positive group (n=33) were compared. Non-Candida and non-Aspergillus fungi infections were more frequent in the conventional-negative/sequencing-positive group (p-value = 0.031). We demonstrated the presence of rare human pathogens, such as Trichosporon asahii and Phycomyces blakesleeanus. In the 'Fungal infection' group and 'Fungal colonization' group, sequencing was faster than culturing (mean difference = 4.92 days, p-value < 0.001/ mean difference = 4.67, p-value <0.001). Compared to the conventional diagnostic methods including culture, nanopore amplicon sequencing showed a shorter turnaround time and a higher detection rate for uncommon fungal pathogens.

Comprehensive analysis of predominant pathogenic bacteria and viruses in seafood products.

Given the growing global demand for seafood, it is imperative to conduct a comprehensive study on the prevalence and persistence patterns of pathogenic bacteria and viruses associated with specific seafood varieties. This assessment thoroughly examines the safety of seafood products, considering the diverse processing methods employed in the industry. The importance of understanding the behavior of foodborne pathogens, such as Salmonella typhimurium, Vibrio parahaemolyticus, Clostridium botulinum, Listeria monocytogenes, human norovirus, and hepatitis A virus, is emphasized by recent cases of gastroenteritis outbreaks linked to contaminated seafood. This analysis examines outbreaks linked to seafood in the United States and globally, with a particular emphasis on the health concerns posed by pathogenic bacteria and viruses to consumers. Ensuring the safety of seafood is crucial since it directly relates to consumer preferences on sustainability, food safety, provenance, and availability. The review focuses on assessing the frequency, growth, and durability of infections that arise during the processing of seafood. It utilizes next-generation sequencing to identify the bacteria responsible for these illnesses. Additionally, it analyzes methods for preventing and intervening of infections while also considering the forthcoming challenges in ensuring the microbiological safety of seafood products. This evaluation emphasizes the significance of the seafood processing industry in promptly responding to evolving consumer preferences by offering current information on seafood hazards and future consumption patterns. To ensure the continuous safety and sustainable future of seafood products, it is crucial to identify and address possible threats.