Association between heavy metal exposure and biomarkers for non-alcoholic fatty liver disease in Korean adolescents.

Objectives: The global prevalence of non-alcoholic fatty liver disease (NAFLD) in adolescents has increased. In addition to childhood obesity, environmental risk factors, such as heavy metals that are known to be involved in hepatotoxicity, play role in NAFLD occurrence. However, their association with NAFLD remains unclear. This study aimed to investigate the association between heavy metal exposure and NAFLD biomarkers in adolescents. Methods: In this cross-sectional study, we used the data of a total of 1505 adolescents aged 12-17 years who participated in the Korean National Environmental Health Survey III (2015-2017) and IV (2018-2020). The presence of blood lead (BPb), blood mercury (BHg), urinary mercury (UHg), and urinary cadmium (UCd) were measured. Liver enzymes including serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT) were evaluated. For NAFLD biomarkers, the hepatic steatosis index (HSI) was calculated. Multivariate linear regression models, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) model were used to investigate the association between heavy metals and NAFLD biomarkers. Results: Among heavy metals, mercury presence showed a significant association with NAFLD biomarkers. Two-fold increases in BHg and UHg were associated with 0.21 points (95 % confidence interval [CI]: 0.08-0.35) and 0.19 points (95 % CI: 0.09-0.30) higher HSI, respectively. In the WQS model, heavy metal mixture was significantly associated with increased HSI (ß = 0.06, 95 % CI: 0.01-0.11). Similarly, in the BKMR model, heavy metal mixture was positively associated with NAFLD biomarkers, and BHg was the most important contributor in the association. Conclusions: BHg and UHg were significantly associated with NAFLD biomarkers in adolescents, indicating that organic and inorganic mercury exposure could potentially be a risk factor for NAFLD. To mitigate and address the risk of NAFLD associated with heavy metal exposure, it is imperative to take measure to reduce avoidable mercury exposure is necessary.

Limnichthyskoreanus, a new species of creediid fish (Teleostei, Acropomatiformes, Creediidae) from Korea.

Limnichthyskoreanus sp. nov. is described on the basis of the holotype and 11 paratypes from subtidal waters of Seogwipo, Jeju Island, Korea. The new species had previously been regarded as the Northern Hemisphere population of the anti-equatorial L.fasciatus, but molecular analyses of mitochondrial COI and 16S genes recovers deep genetic divergences of 9.4% and 15.0% between the new species and topotypical specimens of L.fasciatus. Limnichthyskoreanus sp. nov. is distinguished from all other species of Limnichthys based on the following combination of colouration and morphological characteristics: 38-40 vertebrae; 0-6 dorsal saddles joining mid-lateral stripe; small infraorbital sensory pores; a single median interorbital pore; and well-developed vomerine teeth. Summary characters for comparative congeneric species are provided.

Acupuncture as Adjuvant Therapy for Glaucoma: Protocol for a Randomized Controlled Trial.

BACKGROUND: Glaucoma is a chronic progressive optic neuropathy that necessitates lifelong treatment to reduce the decline of the optic nerve. Due to the extended and continuous treatments required for patients, complementary therapies are often considered alongside conventional treatments to enhance the effectiveness of the treatment. Acupuncture has demonstrated the potential to lower intraocular pressure in previous clinical trials, making it a promising glaucoma intervention. OBJECTIVE: The primary objective of this study is to conduct a single-center randomized control trial involving patients with glaucoma. Acupuncture will be evaluated as an adjunctive therapy. The trial aims to explore its effectiveness for glaucoma. METHODS: In this single-center randomized controlled trial, participants (N=50) with primary open-angle glaucoma will be randomly assigned to the treatment group, receiving ophthalmic acupuncture with "De Qi" sensation, or the control group, receiving minimum acupuncture stimulation on nonophthalmic acupoints. The intervention will consist of weekly acupuncture treatments for a total of 6 sessions. Participants will be assessed at 8 time points, which are baseline, during the intervention (6 times), and at a 3-month follow-up. The primary outcome measure is a change in the intraocular pressure before and after each acupuncture treatment. Secondary outcomes will include measurements of heart rate and blood pressure before and after acupuncture, best-corrected visual acuity, visual field, optical coherence tomography, optical coherence tomography angiography, the Glaucoma Symptom Scale, and the Glaucoma Quality of Life-15 questionnaire. RESULTS: Recruitment of participants for the trial commenced on June 28, 2023. A total of 10 participants have been enrolled to test the feasibility of the experiment. We anticipate that the preliminary data from this trial will be completed by December 2025. CONCLUSIONS: This trial uses rigorous methodology and comprehensive outcome measurements to assess the clinical efficacy of acupuncture as an adjunctive therapy for glaucoma, providing valuable insights for future clinical treatment guidelines. TRIAL REGISTRATION: ClinicalTrials.gov NCT05753137; https://clinicaltrials.gov/study/NCT05753137. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/57888.

SARS-CoV2 mRNA vaccine intravenous administration induces myocarditis in chronic inflammation.

The current COVID-19 mRNA vaccines were developed and applied for pandemic-emergent conditions. These vaccines use a small piece of the virus's genetic material (mRNA) to stimulate an immune response against COVID-19. However, their potential effects on individuals with chronic inflammatory conditions and vaccination routes remain questionable. Therefore, we investigated the effects of mRNA vaccines in a mouse model of chronic inflammation, focusing on their cardiac toxicity and immunogenicity dependent on the injection route. mRNA vaccine intravenous administration with or without chronic inflammation exacerbated cardiac pericarditis and myocarditis; immunization induced mild inflammation and inflammatory cytokine IL-1beta and IL-6 production in the heart. Further, IV mRNA vaccination induced cardiac damage in LPS chronic inflammation, particularly serum troponin I (TnI), which dramatically increased. IV vaccine administration may induce more cardiotoxicity in chronic inflammation. These findings highlight the need for further research to understand the underlying mechanisms of mRNA vaccines with chronic inflammatory conditions dependent on injection routes.

Maternal exposure to airborne particulate matter during pregnancy and lactation induces kidney injury in rat dams and their male offspring: the role of vitamin D in pregnancy and beyond.

BACKGROUND: Little is known about the transgenerational effects of maternal exposure to fine particulate matter (PM2.5) on offspring kidney health. This study investigated the effect of maternal administration of PM2.5 or PM2.5 with vitamin D during pregnancy and lactation on renal injury in rat dams and their offspring. METHODS: Nine pregnant Sprague-Dawley rats received oral administration of normal saline, airborne PM2.5, or PM2.5 with vitamin D from gestational day 11 to postpartum day 21. Kidneys of rat dams (n = 3 for each group) and their male offspring (n = 5 for each group) were taken for analysis on postpartum or postnatal day 21. RESULTS: Maternal PM2.5 exposure increased glomerular damage, tubulointerstitial injury, and cortical macrophage infiltration in both dams and pups; all increases were attenuated by vitamin D administration. In dam kidneys, PM2.5 increased the protein expression of vitamin D receptor (VDR), klotho, and tumor necrosis factor-α; vitamin D lessened these changes. The expressions of renin, nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear factor-kappa B (NF-κB) p50 decreased in rat dams exposed to PM2.5. In offspring kidneys, exposure to maternal PM2.5 reduced the expression of VDR, renin, angiotensin-converting enzyme (ACE), Nrf2, and NF-κB p50, but increased cytochrome P450 24A1 expression. Maternal vitamin D administration with PM2.5 enhanced VDR, ACE, and NF-κB p50 activities in pup kidneys. CONCLUSION: PM2.5 exposure during nephrogenesis may exert transgenerational renal impairment, and maternal vitamin D intake could attenuate PM2.5-induced kidney damage in mothers and their offspring.

RFC2 may contribute to the pathogenicity of Williams syndrome revealed in a zebrafish model.

Williams syndrome (WS) is a rare multisystemic disorder caused by recurrent microdeletions on 7q11.23, characterized by intellectual disability, distinctive craniofacial and dental features, and cardiovascular problems. Previous studies have explored the roles of individual genes within these microdeletions in contributing to WS phenotypes. Here, we report five patients with WS with 1.4 Mb-1.5 Mb microdeletions that include RFC2, as well as one patient with a 167 kb microdeletion involving RFC2 and six patients with intragenic variants within RFC2. To investigate the potential involvement of RFC2 in WS pathogenicity, we generate a rfc2 knockout (KO) zebrafish using CRISPR-Cas9 technology. Additionally, we generate a KO zebrafish of its paralog gene, rfc5, to better understand the functions of these RFC genes in development and disease. Both rfc2 and rfc5 KO zebrafish exhibit similar phenotypes reminiscent of WS, including small head and brain, jaw and dental defects, and vascular problems. RNA-seq analysis reveals that genes associated with neural cell survival and differentiation are specifically affected in rfc2 KO zebrafish. In addition, heterozygous rfc2 KO adult zebrafish demonstrate an anxiety-like behavior with increased social cohesion. These results suggest that RFC2 may contribute to the pathogenicity of Williams syndrome, as evidenced by the zebrafish model.

Emergency department laparotomy for patients with severe abdominal trauma: a retrospective study at a single regional trauma center in Korea.

Purpose: Severe abdominal injuries often require immediate clinical assessment and surgical intervention to prevent life-threatening complications. In Jeju Regional Trauma Center, we have instituted a protocol for emergency department (ED) laparotomy at the trauma bay. We investigated the mortality and time taken from admission to ED laparotomy. Methods: We reviewed the data recorded in our center's trauma database between January 2020 and December 2022 and identified patients who underwent laparotomy because of abdominal trauma. Laparotomies that were performed at the trauma bay or the ED were classified as ED laparotomy, whereas those performed in the operating room (OR) were referred to as OR laparotomy. In cases that required expeditious hemostasis, ED laparotomy was performed appropriately. Results: From January 2020 to December 2022, 105 trauma patients admitted to our hospital underwent emergency laparotomy. Of these patients, six (5.7%) underwent ED laparotomy. ED laparotomy was associated with a mortality rate of 66.7% (four of six patients), which was significantly higher than that of OR laparotomy (17.1%, 18 of 99 patients, P=0.006). All the patients who received ED laparotomy also underwent damage control laparotomy. The time between admission to the first laparotomy was significantly shorter in the ED laparotomy group (28.5 minutes; interquartile range [IQR], 14-59 minutes) when compared with the OR laparotomy group (104 minutes; IQR, 88-151 minutes; P<0.001). The two patients who survived after ED laparotomy had massive mesenteric bleeding, which was successfully ligated. The other four patients, who had liver laceration, kidney rupture, spleen injury, and pancreas avulsion, succumbed to the injuries. Conclusions: Although ED laparotomy was associated with a higher mortality rate, the time between admission and ED laparotomy was markedly shorter than for OR laparotomy. Notably, major mesenteric hemorrhages were effectively controlled through ED laparotomy.

Apurinic/apyrimidinic endonuclease 1 alleviates inflammation in fibroblast-like synoviocytes from patients with rheumatoid arthritis.

Introduction: Apurinic/apyrimidinic endonuclease 1 (APEX1) is a protein with elevated expression in synovial fluids from rheumatoid arthritis (RA) patients. However, its role in RA pathogenesis remains unexplored. This study investigated the influence of APEX1 on inflammatory pathways in fibroblast-like synoviocytes (FLS) isolated from RA patients. Material and methods: FLS from RA patients (n = 5) were stimulated with recombinant tumor necrosis factor α (TNF-α) and interleukin (IL)-17. Subsequently, cells were treated with recombinant APEX1, and assessments were made on reactive oxygen species (ROS) production and mitochondrial membrane potential. Additionally, mRNA levels of IL-1 family members were quantified. Cell migration was evaluated through Transwell chamber assays, and levels of key secreted inflammatory cytokines were measured via enzyme-linked immunosorbent assay (ELISA). Results: The results demonstrated that APEX1 significantly reduced mitochondrial-specific ROS expression and restored mitochondrial membrane potential in TNF-α/IL-17-stimulated RA FLS. Furthermore, APEX1 treatments attenuated TNF-α/IL-17-induced activation of p38 MAPK, NF-κB, and PI3K 110 δ signaling pathways. Similarly, APEX1 significantly diminished TNF-α/IL-17-induced expression of inflammatory cytokines, including IL-1 family members, IL-6, IL-8, and vascular endothelial growth factor (VEGF). Notably, APEX1 downregulated cell migration of TNF-α/IL-17-treated RA FLS via inhibition of matrix metalloproteinase 3 (MMP3). Conclusions: These findings collectively underscore the role of APEX1 as a key mediator of cytokine-amplified migration, modulating ROS and MMP3 in RA FLS, thus supporting its potential as a therapeutic target in RA treatment.

Framingham risk score is a useful indicator of posttransplant cardiovascular events and survival among Korean kidney transplant recipients: a nationwide, prospective cohort study.

Background: Cardiovascular disease is an important risk factor for mortality among kidney transplant recipients. In this study, we aimed to investigate the association between cardiovascular risk score at kidney transplantation and long-term outcomes of patients. Methods: In this prospective, observational cohort study, we enrolled kidney transplant recipients who participated in the Korean Organ Transplantation Registry and underwent transplantation between April 2014 and December 2019. The cardiovascular risk status of kidney transplant recipients was assessed using the Framingham risk score. All-cause mortality, major adverse cardiovascular events, allograft failure, estimated glomerular filtration rates (eGFRs), and composite outcomes were evaluated after kidney transplantation. Results: Of the 4,682 kidney transplant recipients, 96 died during 30.7 ± 19.1 months of follow-up. The Kaplan-Meier survival analysis results showed that high Framingham risk scores were associated with all-cause mortality, major adverse cardiovascular events, and composite outcomes. According to the multivariable Cox analysis, high Framingham risk scores were associated with an increased risk of mortality (hazard ratio [HR], 3.20; 95% confidence interval [CI], 1.30-7.91), major adverse cardiovascular events (HR, 8.43; 95% CI, 2.41-29.52), and composite outcomes (HR, 2.05; 95% CI, 1.19-3.46). The eGFRs after transplantation were significantly higher among patients in the low Framingham risk score group (p < 0.001). However, Framingham risk scores were not associated with graft loss or rapid decline in eGFRs. Conclusion: The Framingham risk score is a useful indicator of cardiovascular events, mortality, and kidney function after kidney transplantation.

Acupuncture treatment is associated with a decreased risk of dementia in patients with rheumatoid arthritis in Taiwan: A propensity-score matched cohort study.

Background: The purpose of this study was to understand whether acupuncture can decrease the risk of dementia in patients with rheumatoid arthritis (RA). Methods: Using the registry from the National Health Insurance Research Database of Taiwan, we carried out a 1:1 propensity-score matched cohort study to analyze patients with RA diagnosed between 2000 and 2010. The patients who received acupuncture therapy were grouped as acupuncture users (n = 9,919), while the others were grouped as non-acupuncture users (n = 19,331). After propensity-score matching, the final sample included 9,218 matched participants in both groups, and these participants were followed up until the end of 2011. We used a Cox regression model to adjust for age, sex, comorbidiy, and conventional drugs and compared the hazard ratios (HRs) of developing dementia in the acupuncture and non-acupuncture groups. Results: Acupuncture users tended to be more female-dominant and younger than non-acupuncture users. After propensity-score matching, both groups have comparable demographic characteristics. Acupuncture users had a lower risk of dementia than non-acupuncture users (adjusted HR: 0.55, 95% CI: 0.46-0.66). The cumulative incidence of dementia in the acupuncture group was significantly lower than that in the non-acupuncture group (log-rank test, p < 0.001). Patients who received the combinational treatment of conventional drugs and acupuncture had a significantly lower risk of developing dementia (adjusted HR: 0.64, 95% CI: 0.56-0.73) compared to those who only received conventional drugs. Conclusion: Acupuncture therapy is associated with a reduced risk of dementia in patients with RA. Further clinical and mechanistic studies are needed.

Optimization of Electroporation Conditions for Introducing Heterologous DNA into Rhodobacter sphaeroides.

Rhodobacter sphaeroides is a strain capable of both photoautotrophic and chemoautotrophic growth, with various metabolic pathways that make it highly suitable for converting carbon dioxide into high value-added products. However, its low transformation efficiency has posed challenges for genetic and metabolic engineering of this strain. In this study, we aimed to increase the transformation efficiency of R. sphaeroides by deleting the rshI gene coding for an endogenous DNA restriction enzyme that inhibits. We evaluated the effects of growth conditions for making electrocompetent cells and optimized electroporation parameters to be a cuvette width of 0.1 cm, an electric field strength of 30 kV/cm, a resistance of 200 Ω, and a plasmid DNA amount of 0.5 µg, followed by a 24-h recovery period. As a result, we observed over 7,000 transformants per µg of DNA under the optimized electroporation conditions using the R. sphaeroides ΔrshI strain, which is approximately 10 times higher than that of wild-type R. sphaeroides under standard bacterial electroporation conditions. These findings are expected to enhance the application of R. sphaeroides in various industrial fields in the future.

Comparative associations of MASLD and MAFLD with the presence and severity of coronary artery calcification.

We aimed to compare the associations of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) with coronary artery calcification (CAC). Patients who simultaneously underwent ultrasonography to diagnose hepatic steatosis and cardiac computed tomography to detect CAC were included. The presence and severity of CAC were defined with CAC-score thresholds of > 0 and > 300, respectively, and patients were divided into the following groups: no MASLD or MAFLD (reference), MASLD-only, MAFLD-only, and overlapping groups. Overall, 1,060/2,773 (38.2%) patients had CAC, of which 196 (18.5%) had severe CAC. The MASLD and MAFLD prevalence rates were 32.6% and 45.2%, respectively, with an overlap of 30.7%. In an ASCVD risk score-adjusted model, both MASLD (adjusted odd ratios [aOR], 1.21; 95% confidence interval [CI], 1.02-1.44; p = 0.033) and MAFLD (aOR 1.20; 95% CI 1.01-1.42, p = 0.034) were associated with CAC, whereas only MASLD (aOR 1.38; 95% CI 1.01-1.89, p = 0.041) was associated with severe CAC. Compared to the reference group, the overlapping group showed an association with CAC (aOR 1.22; 95% CI 1.01-1.47; p = 0.038); however, the MASLD and MAFLD subgroups did not differ in their association with CAC. MASLD may predict a higher risk of ASCVD more effectively than MAFLD.

Suppressing Hole Accumulation Through Sub-Nanometer Dipole Interfaces in Hybrid Perovskite/Organic Solar Cells for Boosting Near-Infrared Photon Harvesting.

The potential of hybrid perovskite/organic solar cells (HSCs) is increasingly recognized owing to their advantageous characteristics, including straightforward fabrication, broad-spectrum photon absorption, and minimal open-circuit voltage (VOC) loss. Nonetheless, a key bottleneck for efficiency improvement is the energy level mismatch at the perovskite/bulk-heterojunction (BHJ) interface, leading to charge accumulation. In this study, it is demonstrated that introducing a uniform sub-nanometer dipole layer formed of B3PyMPM onto the perovskite surface effectively reduces the 0.24 eV energy band offset between the perovskite and the donor of BHJ. This strategic modification suppresses the charge recombination loss, resulting in a noticeable 30 mV increase in the VOC and a balanced carrier transport, accompanied by a 5.0% increase in the fill factor. Consequently, HSCs that achieve power conversion efficiency of 24.0% is developed, a new record for Pb-based HSCs with a remarkable increase in the short-circuit current of 4.9 mA cm-2, attributed to enhanced near-infrared photon harvesting.

Novel Roles of Catalysts in Producing High-purity High-pressure Hydrogen from Sodium Borohydride.

Hydrogen has received enormous attention as a clean fuel with its high specific energy (142 MJ/kg). To apply hydrogen as a practically available energy vector, the direct production of high-pressure hydrogen with high purity is pivotal, as it allows for circumventing the mechanical compression process. Recently, the concept of utilizing sodium borohydride (SBH) dehydrogenation as a chemical compressor that can generate high-pressure hydrogen gas was demonstrated by adopting formic acid as an acid catalyst. However, the presence of impurities (e.g., CO, CO2) in the final gas product requires an alternative method to enhance the use of SBH as a chemical compressor. Here, we highlighted the feasibility of producing high-purity, high-pressure hydrogen gas from the SBH dehydrogenation with and without Co-based catalysts. The scrutiny behind the thermodynamics and kinetics of the SBH dehydrogenation was conducted under the elevated pressure condition. As a result, the dual roles of the catalysts as proton collectors and heat sources were revealed, both of which are essential for improving hydrogen production efficiency. We hope that our research stimulates subsequent research that pave the way to exploit hydrogen as an energy vector and achieve a more sustainable future society.

Paclitaxel-resistance facilitates glycolytic metabolism via Hexokinase-2-regulated ABC and SLC transporter genes in ovarian clear cell carcinoma.

Ovarian clear cell carcinoma (OCCC) frequently develops resistance to platinum-based therapies, which is regarded as an aggressive subtype. However, metabolic changes in paclitaxel resistance remain unclear. Herein, we present the metabolic alternations of paclitaxel resistance in bioenergetic profiling in OCCC. Paclitaxel-resistant OCCC cells were developed and metabolically active with oxygen consumption rates (OCR) compared to parental cells. Metabolite profiling analysis revealed that paclitaxel-resistant OCCC cells reduced intracellular ATP and GTP influx rates, increasing the NADH/NAD+ ratio. We further demonstrated that paclitaxel-resistant OCCC cells led to characteristic alternations of metabolite levels in energy-requiring and energy-releasing steps of glycolysis and their corresponding glycolytic enzymes. Copy number alterations and RNA sequencing analysis demonstrated that ATP-binding cassette (ABC) transporters and solute carrier (SLC) transporter genes involved in glycolysis metabolism and molecular transport were enriched in paclitaxel-resistant OCCC cells. We first identified that Hexokinase 2 (HK2) expression is upregulated in paclitaxel-resistant OCCC cells to determine the quantity of glucose entering glycolysis. Utilizing proteolysis-targeting chimera (PROTAC) HK2 degraders, we also found that paclitaxel sensitivity, viability, and oxygen consumption rates under paclitaxel treatment were restored by HK2 degraders treatment, and decreased downstream expression of the ABC and SLC transporters was shown in OCCC cells. Taken together, these findings highlight the paclitaxel resistance in OCCC elucidates metabolic alternation, including ABC- and SLC- drug transporters, thereby affecting glycolysis metabolism in response to paclitaxel resistance, and HK2 may become a novel potential therapeutic target for paclitaxel resistance.

The application of machine learning for identifying frailty in older patients during hospital admission.

BACKGROUND: Early identification of frail patients and early interventional treatment can minimize the frailty-related medical burden. This study investigated the use of machine learning (ML) to detect frailty in hospitalized older adults with acute illnesses. METHODS: We enrolled inpatients of the geriatric medicine ward at Taichung veterans general hospital between 2012 and 2022. We compared four ML models including logistic regression, random forest (RF), extreme gradient boosting, and support vector machine (SVM) for the prediction of frailty. The feature window as well as the prediction window was set as half a year before admission. Furthermore, Shapley additive explanation plots and partial dependence plots were used to identify Fried's frailty phenotype for interpreting the model across various levels including domain, feature, and individual aspects. RESULTS: We enrolled 3367 patients. Of these, 2843 were frail. We used 21 features to train the prediction model. Of the 4 tested algorithms, SVM yielded the highest AUROC, precision and F1-score (78.05%, 94.53% and 82.10%). Of the 21 features, age, gender, multimorbidity frailty index, triage, hemoglobin, neutrophil ratio, estimated glomerular filtration rate, blood urea nitrogen, and potassium were identified as more impactful due to their absolute values. CONCLUSIONS: Our results demonstrated that some easily accessed parameters from the hospital clinical data system can be used to predict frailty in older hospitalized patients using supervised ML methods.

Accurate prediction of antimicrobial resistance and genetic marker of Staphylococcus aureus clinical isolates using MALDI-TOF MS and machine learning - across DRIAMS and Taiwan database.

BACKGROUND: The use of matrix-assisted laser desorption/ionisation-time-of-flight mass spectra (MALDI-TOF MS) with machine learning (ML) has been explored for predicting antimicrobial resistance. This study evaluates the effectiveness of MALDI-TOF MS paired with various ML classifiers and establishes optimal models for predicting antimicrobial resistance and the presence of mecA gene among Staphylococcus aureus. MATERIALS AND METHODS: Antimicrobial resistance against tier 1 antibiotics and MALDI-TOF MS of S. aureus were analysed using data from the Database of Resistance against Antimicrobials with MALDI-TOF Mass Spectrometry (DRIAMS) and one medical centre (CS database). Five ML classifiers were used to analyse performance metrics. The Shapley value quantified the predictive contribution of individual features. RESULTS: The LightGBM demonstrated superior performance in predicting antimicrobial resistance for most tier 1 antibiotics among oxacillin-resistant S. aureus (ORSA) compared with all S. aureus and oxacillin-susceptible S. aureus (OSSA) in both databases. In DRIAMS, Multilayer Perceptron (MLP) was associated with excellent predictive performance, expressed as accuracy/AUROC/AUPR, for clindamycin (0.74/0.81/0.90), tetracycline (0.86/0.87/0.94), and trimethoprim-sulfamethoxazole (0.95/0.72/0.97). In the CS database, Ada and Light Gradient Boosting Machine (LightGBM) showed excellent performance for erythromycin (0.97/0.92/0.86) and tetracycline (0.68/0.79/0.86). Mass-to-charge ratio (m/z) features of 2411-2414 and 2429-2432 correlated with clindamycin resistance, whereas 5033-5036 was linked to erythromycin resistance in DRIAMS. In the CS database, overlapping features of 2423-2426, 4496-4499, and 3764-3767 simultaneously predicted the presence of mecA and oxacillin resistance. CONCLUSION: The predictive performance of antimicrobial resistance against S. aureus using MALDI-TOF MS depends on database characteristics and the ML algorithm selected. Specific and overlapping mass spectra features are excellent predictive markers for mecA and specific antimicrobial resistance.

Impacts of Atlantic meridional overturning circulation weakening on Arctic amplification.

Enhanced warming of the Arctic region relative to the rest of the globe, known as Arctic amplification, is caused by a variety of diverse factors, many of which are influenced by the Atlantic meridional overturning circulation (AMOC). Here, we quantify the role of AMOC changes in Arctic amplification throughout the twenty-first century by comparing two suites of climate model simulations under the same climate change scenario but with two different AMOC states: one with a weakened AMOC and another with a steady AMOC. We find that a weakened AMOC can reduce annual mean Arctic warming by 2 °C by the end of the century. A primary contributor to this reduction in warming is surface albedo feedback, related to a smaller sea ice loss due to AMOC slowdown. Another major contributor is the changes in ocean heat uptake. The weakened AMOC and its associated anomalous ocean heat transport divergence lead to increased ocean heat uptake and surface cooling. These two factors are inextricably linked on seasonal timescales, and their relative importance for Arctic amplification can vary by season. The weakened AMOC can also abate Arctic warming via lapse rate feedback, creating marked cooling from the surface to lower-to-mid troposphere while resulting in relatively weaker cooling in the upper troposphere. Additionally, the weakened AMOC increases the low-level cloud fraction over the North Atlantic warming hole, causing significant cooling there via shortwave (sw) cloud feedback despite the overall effect of sw cloud feedback being a slight warming of the average temperature over the Arctic.

Effects of Sildenafil on Cognitive Function Recovery and Neuronal Cell Death Protection after Transient Global Cerebral Ischemia in Gerbils.

Cerebral ischemic stroke is a major cause of death worldwide due to brain cell death resulting from ischemia-reperfusion injury. However, effective treatment approaches for patients with ischemic stroke are still lacking in clinical practice. This study investigated the potential neuroprotective effects of sildenafil, a phosphodiesterase-5 inhibitor, in a gerbil model of global brain ischemia. We investigated the effects of sildenafil on the expression of glial fibrillary acidic protein and aquaporin-4, which are markers related to astrocyte activation and water homeostasis, respectively. Immunofluorescence analysis showed that the number of cells co-expressing these markers, which was elevated in the ischemia-induced group, was significantly reduced in the sildenafil-treated groups. This suggests that sildenafil may have a potential mitigating effect on astrocyte activation induced by ischemia. Additionally, we performed various behavioral tests, including the open-field test, novel object recognition, Barnes maze, Y-maze, and passive avoidance tests, to evaluate sildenafil's effect on cognitive function impaired by ischemia. Overall, the results suggest that sildenafil may serve as a neuroprotective agent, potentially alleviating delayed neuronal cell death and improving cognitive function impaired by ischemia.