Blood urea nitrogen to albumin ratio is a novel predictor of fatal outcome for patients with severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is associated with a high death rate and lacks a targeted therapy plan. The ratio of blood urea nitrogen to albumin, known as BAR, is a valuable method for assessing the outlook of various infectious diseases. The objective of this research was to evaluate the effectiveness of BAR in forecasting the outcome of individuals with SFTS. Four hundred and thirty-seven patients with SFTS from two clinical centers were included in this study according to inclusion and exclusion criteria. Clinical characteristics and test parameters of SFTS patients were analyzed between survival and fatal groups. Least absolute shrinkage and selection operator (LASSO) regression and Cox regression suggested that BAR might serve as a standalone prognostic indicator for patients with SFTS in the initial phase (hazard ratio = 18.669, 95% confidence interval [CI]: 8.558-40.725, p < 0.001). And BAR had a better predictive effectiveness in clinical outcomes in patients with SFTS with an AUC of 0.832 (95% CI: 0.788-0.876, p < 0.001), a cutoff value of 0.19, a sensitivity of 0.812, and a specificity of 0.726 compared to C-reactive protein, procalcitonin, and platelet to lymphocyte ratio via receiver operating characteristic curve. KM (Kaplan Meier) curves demonstrated that high level of BAR was associated with poor survival condition in patients with SFTS. Furthermore, the high level of BAR was associated with long hospital stays and test paraments of kidney, liver, and coagulation function in survival patients. So, BAR could be used as a promising early warning biomarker of adverse outcomes in patients with SFTS.

The prognostic value of the stress hyperglycemia ratio for all-cause and cardiovascular mortality in patients with diabetes or prediabetes: insights from NHANES 2005-2018.

BACKGROUND: The Stress hyperglycemia ratio (SHR) is a novel marker reflecting the true acute hyperglycemia status and is associated with clinical adverse events. The relationship between SHR and mortality in patients with diabetes or prediabetes is still unclear. This study aimed to investigate the predictive value of the SHR for all-cause and cardiovascular mortality in patients with diabetes or prediabetes. METHODS: This study included 11,160 patients diagnosed with diabetes or prediabetes from the National Health and Nutrition Examination Survey (2005-2018). The study endpoints were all-cause and cardiovascular mortality, and morality data were extracted from the National Death Index (NDI) up to December 31, 2019. Patients were divided into SHR quartiles. Cox proportion hazards regression was applied to determine the prognostic value of SHR. Model 1 was not adjusted for any covariates. Model 2 was adjusted for age, sex, and race. Model 3 was adjusted for age, sex, race, BMI, smoking status, alcohol use, hypertension, CHD, CKD, anemia, and TG. RESULTS: During a mean follow-up of 84.9 months, a total of 1538 all-cause deaths and 410 cardiovascular deaths were recorded. Kaplan-Meier survival analysis showed the lowest all-cause mortality incidence was in quartile 3 (P < 0.001). Multivariate Cox regression analyses indicated that, compared to the 1st quartile, the 4th quartile was associated with higher all-cause mortality (model 1: HR = 0.89, 95% CI 0.74-10.7, P = 0.226; model 2: HR = 1.24, 95% CI 1.03-1.49, P = 0.026; model 3: HR = 1.30, 95% CI 1.08-1.57, P = 0.006). The 3rd quartile was associated with lower cardiovascular mortality than quartile 1 (model 1: HR = 0.47, 95% CI 0.32-0.69, P < 0.001; model 2: HR = 0.66, 95% CI 0.45-0.96, P = 0.032; model 3: HR = 0.68, 95% CI 0.46-0.99, P = 0.049). There was a U-shaped association between SHR and all-cause mortality and an L-shaped association between SHR and cardiovascular mortality, with inflection points of SHR for poor prognosis of 0.87 and 0.93, respectively. CONCLUSION: SHR is related to all-cause and cardiovascular mortality in patients with diabetes or prediabetes. SHR may have predictive value in those patients.

Relative efficacy of antibody-drug conjugates and other anti-HER2 treatments on survival in HER2-positive advanced breast cancer: a systematic review and meta-analysis.

BACKGROUND: Novel antibody-drug conjugates (ADCs) drugs present a promising anti-cancer treatment, although survival benefits for HER2-positive advanced breast cancer (BC) remain controversial. The aim of this meta-analysis was to evaluate the comparative effect of ADCs and other anti-HER2 therapy on progression-free survival (PFS) and overall survival (OS) for treatment of HER2-positive locally advanced or metastatic BC. METHODS: Relevant randomized controlled trials (RCTs) were retrieved from five databases. The risk of bias was assessed with the Cochrane Collaboration's tool for RCTs by RevMan5.4 software. The hazard ratio (HR) and 95% confidence intervals (CIs) were extracted to evaluate the benefit of ADCs on PFS and OS in HER2-positive advanced BC by meta-analysis. RESULTS: Meta-analysis of six RCTs with 3870 patients revealed that ADCs significantly improved PFS (HR: 0.63, 95% CI: 0.49-0.80, P = 0.0002) and OS (HR: 0.79, 95% CI: 0.72-0.86, P < 0.0001) of patients with HER2-positive locally advanced or metastatic BC. Subgroup analysis showed that PFS and OS were obviously prolonged for patients who previously received HER2-targeted therapy. Sensitivity analysis and publication bias suggested that the results were stable and reliable. CONCLUSION: Statistically significant benefits for PFS and OS were observed with ADCs in HER2-positive locally advanced or metastatic BC, especially for those who received prior anti-HER2 treatment.

Selective Modifier-Assisted Humic Acid Extraction: Implications for Soil Quality Enhancement.

Efficient use of humic acid (HA) for eco-friendly farming and environmental remediation requires further understanding of how targeted modification of HA affects the chemical structure of HA and thereby its effectiveness in enhancing soil quality. We developed novel selective modifiers (SMs) for extracting HA by codoping sodium and copper elements into the birnessite lattice. The structure of SMs was thoroughly examined, and the HAs extracted using SMs, referred to as SMHs, were subjected to a detailed evaluation of their functional groups, molecular weight, carbon composition, flocculation limits, and effectiveness in saline soil remediation. The results showed that replacing manganese with sodium and copper in SMs alters the valence state and reactive oxygen species. In contrast, SMHs exhibited increased acidic functional groups, a lower molecular weight, and transformed aliphatic carbon. Furthermore, the saline soil was improved through increased salt leaching and an optimized soil aggregate structure by SMHs. This research highlights the importance of targeted modification of HA and demonstrates the potential of these modifiers in improving soil quality for eco-friendly farming and environmental remediation.

A training program for improving the capacity of infection high-throughput sequencing and diagnosis in China.

BACKGROUND: Infectious diseases are a serious threat to human especially since the COVID-19 outbreak has proved the importance and urgency of their diagnosis and treatment again. Metagenomic next-generation sequencing (mNGS) has been widely used and recognized in clinical and carried out localized testing in hospitals. Increasing the training of mNGS detection technicians can enhance their professional quality and more effectively realize the application value of the hospital platform. METHODS: Based on the initial theoretical understanding and practice of the mNGS platform for localization construction, we have designed a training program to enhance the ability of technicians to detect pathogens by utilizing mNGS, and hence to conduct training practices nationwide. RESULTS: Until August 30, 2022, the page views of online classes have reached 51,500 times and 6 of offline small-scale training courses have been conducted. A total of 67 trainees from 67 hospitals have participated in the training with a qualified rate of 100%. After the training course, the localization platform of 1 participating hospital has been put into use, 2 have added the mNGS localization platform for admission, among which 3 have expressed strong intention of localization. CONCLUSIONS: This study focuses on the training procedures and practical experience of the project which is the first systematic standardized program of mNGS in the world. It solves the training difficulties in the current industry, and effectively promotes the localization construction and application of mNGS in hospitals. It has great development potential in the future and is worth further promotion.

Safety and effectiveness of a novel dielectric mapping system: one-year, two chinese centers experiences.

BACKGROUND: The KODEX-EPD system is a novel, dielectric three-dimensional mapping system. We aim to illustrate the feasibility, safety, and outcomes of ablation using the KODEX-EPD system. METHODS: A total of 272 patients with supraventricular arrhythmias were enrolled and underwent catheter ablation using the KODEX-EPD system from October 2020 to July 2021. The feasibility, safety, and ablation outcomes were analyzed. RESULTS: Of the enrolled patients, 15 (5.4%) had atrial tachycardia (AT), 88 (31.4%) had atrioventricular reentrant tachycardia (AVRT), 141 (50.4%) had atrioventricular nodal reentrant tachycardia (AVNRT), 34 (12.1%) had atrial fibrillation (AF), and 9 (3.2%) had atrial flutter (AFL). All AF patients included were first-do-pulmonary vein isolation (PVI); there were 26 paroxysmal AF and 8 persistent AF. All patients achieved immediate success of ablation. The mean follow-up duration was 11.8 ± 2.4 months. One patient (1.1%) in the AVRT subgroup and two patients (1.4%) in the AVNRT subgroup experienced recurrence. When considering a three-month blanking time, the estimated freedom of AF at one-year post-ablation with and without AADs was 75.7% and 70.4%, respectively. The Kaplan-Meier analysis showed no significant difference in the overall AF recurrence (log-rank; P = 0.931) or AAD-free AF recurrence (log-rank; P = 0.841) between RFCA and cryoablation. One patient had mild pulmonary embolism. None of the patients died or had a cerebrovascular event in the periprocedural period. CONCLUSIONS: This retrospective, two-center study demonstrated that catheter ablation of supraventricular arrhythmias using the KODEX-EPD system is feasible, safe, and effective. Trial registration Retrospectively registered.

Occluding morphologically complicated left atrial appendage using the small-umbrella LAmbre device.

BACKGROUND: Percutaneous left atrial appendage (LAA) occlusion is effective for stroke prevention in patients with atrial fibrillation. LAA can have a complex anatomy, such as multiple lobes or a large orifice, which may render it unsuitable for occlusion using regular devices. We aimed to investigate the feasibility, safety, and short-term efficacy of the small-umbrella LAmbre device for morphologically complicated LAA. METHODS: We retrospectively enrolled 129 consecutive patients who underwent LAA occlusion using the LAmbre device; the small-umbrella LAmbre device was used in 30 of these patients. We analyzed patients' characteristics, procedural details, and outcomes. RESULTS: Twenty-two patients (73.3%) had multilobed (≥ 2) LAA. The umbrella of the occluder was anchored in the branch in 9 patients and in the common trunks of branches in 13 patients. The landing zone and orifice diameters were 19.0 ± 4.39 mm and 27.4 ± 3.95 mm, respectively. The sizes of the umbrella and occluder cover were 22.0 ± 3.42 mm and 34.3 ± 2.75 mm, respectively. At 3-month follow-up transesophageal echocardiography in 24 patients, no peri-device residual flow was reported. Device thrombosis was detected in one patient at 3 months and disappeared after 3 months of anticoagulation. Ischemic stroke occurred in one patient; no other adverse events were reported. CONCLUSIONS: Occlusion of morphologically complicated LAA using the small-umbrella LAmbre device was feasible, safe, and effective in patients with atrial fibrillation in this study. This occluder provides an alternative for patients who cannot be treated with regular-sized LAA occlusion devices.

Host feces, olfactory beacon guiding aggregation of intestinal parasites Gasterophilus pecorum (Diptera: Gasterophilidae).

The aim of this study was to identify the aggregation sites and transmission characteristics of Gasterophilus pecorum, the dominant pathogen of endangered equines in desert steppe. Therefore, we tested with a four-arm olfactometer the olfactory response of the G. pecorum adults to the odors that have a great impact on their life cycle, and also investigated the occurrence sites of the adults in the area where the Przewalski's horse (Equus przewalskii) roam frequently during the peak period of G. pecorum infection. The results of four-directional olfactory test showed that the fresh horse feces had a stronger attraction rate on both male (50.4%) and female flies (38.2%). Stipa caucasica, the only oviposition plant where G. pecorum lay eggs, had a better attraction effect on females than that on males. And the attraction rates of S. caucasica to G. pecorum females in the early growth stage (Stipa I) and mid-growth stage (Stipa II) were 32.8% and 36.8%, respectively. In addition, the two-directional olfactory test showed that the attraction rate of males to fresh horse feces (68.90%) was higher than that to Stipa II (31.10%), and females also showed similar olfactory responses. Moreover, in our field investigation, 68.29% of G. pecorum adults were collected from around the horse feces. The results of laboratory test and field investigation implied that the location mechanism of G. pecorum aggregation for mating is related to the orientation of horse feces. The horse feces and the vicinity are the key contamination areas of G. pecorum, and it is also the areas where horses are seriously infected with G. pecorum. Those fresh feces, which gather abundant information about the host, naturally had the greatest chance of contacting with the host; G. pecorum adults create the opportunity to enter directly into the host's mouth and infect the host by laying eggs on S. caucasica, which is the most favorite plant of the host in this area. These characteristics are one of the main reasons why G. pecorum has become the dominant species under the condition of sparse vegetation in desert steppe.

Hippocampal hyperactivity in a rat model of Alzheimer's disease.

Neuronal network dysfunction is a hallmark of Alzheimer's disease (AD). However, the underlying pathomechanisms remain unknown. We analyzed the hippocampal micronetwork in transgenic McGill-R-Thy1-APP rats (APPtg) at the beginning of extracellular amyloid beta (Aß) deposition. We established two-photon Ca2+ -imaging in vivo in the hippocampus of rats and found hyperactivity of CA1 neurons. Patch-clamp recordings in brain slices in vitro revealed increased neuronal input resistance and prolonged action potential width in CA1 pyramidal neurons. We did neither observe changes in synaptic inhibition, nor in excitation. Our data support the view that increased intrinsic excitability of CA1 neurons may precede inhibitory dysfunction at an early stage of Aß-deposition and disease progression.

Lymphocyte-monocyte-neutrophil index: a predictor of severity of coronavirus disease 2019 patients produced by sparse principal component analysis.

BACKGROUND: It is important to recognize the coronavirus disease 2019 (COVID-19) patients in severe conditions from moderate ones, thus more effective predictors should be developed. METHODS: Clinical indicators of COVID-19 patients from two independent cohorts (Training data: Hefei Cohort, 82 patients; Validation data: Nanchang Cohort, 169 patients) were retrospected. Sparse principal component analysis (SPCA) using Hefei Cohort was performed and prediction models were deduced. Prediction results were evaluated by receiver operator characteristic curve and decision curve analysis (DCA) in above two cohorts. RESULTS: SPCA using Hefei Cohort revealed that the first 13 principal components (PCs) account for 80.8% of the total variance of original data. The PC1 and PC12 were significantly associated with disease severity with odds ratio of 4.049 and 3.318, respectively. They were used to construct prediction model, named Model-A. In disease severity prediction, Model-A gave the best prediction efficiency with area under curve (AUC) of 0.867 and 0.835 in Hefei and Nanchang Cohort, respectively. Model-A's simplified version, named as LMN index, gave comparable prediction efficiency as classical clinical markers with AUC of 0.837 and 0.800 in training and validation cohort, respectively. According to DCA, Model-A gave slightly better performance than others and LMN index showed similar performance as albumin or neutrophil-to-lymphocyte ratio. CONCLUSIONS: Prediction models produced by SPCA showed robust disease severity prediction efficiency for COVID-19 patients and have the potential for clinical application.

A UPLC-MS/MS method for simultaneous determination of nine antiepileptic drugs in human plasma and its application in TDM.

With the purpose of carrying out therapeutic drug monitoring (TDM) of nine antiepileptic drugs simultaneously in the clinic, a UPLC-MS/MS assay method was developed and validated. Separation of antiepileptic drugs and internal standard (naproxen and diazepam) was performed on an Agilent Eclipse XDB-C18 column (50.0 × 2.1 mm, 1.7 µm) using water and acetonitrile as mobile phase for gradient elution. Polarity switch ionization mode (positive-negative-positive) was performed in a total run time of 3.0 min. The method validation was conducted based on bioanalytical method validation guidance, including specificity, calibration curve, precision, accuracy, recovery, matrix effect, stability and dilution integrity, and all of the results satisfied the requirements. Consequently, the proposed method was applied to the TDM of nine antiepileptic drugs and was proved to be sensitive, reliable and specific to determine antiepileptic drugs in human plasma simultaneously. Meanwhile, the TDM results showed that the plasma drug concentration of many patients was not within the effective therapeutic range, especially those taking topiramate, oxcarbazepine and levetiracetam, which was of great guiding significance to rational drug use and timely adjustment of the treatment plan. Therefore, individualized therapy based on advanced analytical methods and TDM theory is of great practical significance.

Supraventricular tachycardia in patients with coronary sinus stenosis/atresia: Prevalence, anatomical features, and ablation outcomes.

BACKGROUND: Supraventricular tachycardia (SVT) with coronary sinus (CS) ostial atresia (CSA) or coronary sinus stenosis (CSS) causes difficulty in electrophysiological procedures, but its characteristics are poorly understood. OBJECTIVE: Study the anatomical and clinical features of SVT patients with CSA/CSS. METHODS: Of 6128 patients with SVT undergoing electrophysiological procedures, consecutive patients with CSA/CSS were enrolled, and the baseline characteristics, imaging materials, intraoperative data, and follow-up outcomes were analyzed. RESULTS: Thirteen patients, seven with CSA and six with CSS, underwent the electrophysiological procedure. Decapolar catheters were placed into the proximal CS in three cases, while the rest were placed at the free wall of the right atrium. Fourteen arrhythmias were confirmed: four atrioventricular nodal reentrant tachycardias, five left-sided accessory pathways, three paroxysmal atrial fibrillations, and two atrial flutters (AFLs). In addition to three patients who underwent only an electrophysiological study, the acute ablation success rate was 100% in 10 cases, with no procedure-related complications. After a median follow-up period of 59.6 months, only one case of atypical AFL recurred. For those cases (seven CSA and two CSS) with a total of 10 anomalous types of CS drainage, three types were classified: from the CS to the persistent left superior vena cava (n = 3), from an unroofed CS (n = 3), and from the CS to the small cardiac vein (n = 3) or Thebesian vein (n = 1). CONCLUSION: Patients with CSA/CSS may develop different kinds of SVT. Electrophysiological procedures for such patients are feasible and effective. An individualized mapping strategy based on the three types of CS drainage will be helpful.

Quantitative proteomic analysis reveals that Luks-PV exerts antitumor activity by regulating the key proteins and metabolic pathways in HepG2 cells.

Hepatocellular carcinoma (HCC) is a complicated and poor prognosis cancer, necessitating the development of a potential treatment strategy. In this study, we initially revealed that LukS-PV belonged to leukocidin family performs an anti-HCC action. Then, we used liquid chromatography-mass spectrometry (LC/MS) to compare protein expression profiles of the LukS-PV-treated human HCC cell lines HepG2 and the control cells. GO annotations and Kyoto Encyclopedia of Genes and Genomes pathway analysis were carried out of differential expression followed by protein-protein interactome, to explore the underlying cancer suppressor mechanisms of LukS-PV for human HCC. A total of 88 upregulated proteins and 46 downregulated proteins were identified. The top 10 proteins identified by the MCC method are FN1, APP, TIMP1, nucleobindin-1, GOLM1, APLP2, CYR61, CD63, ENG, and CD9. Our observation on protein expression indicated that LukS-PV produces a signature affecting central carbon metabolism in cancer, galactose metabolism, and fructose and mannose metabolism pathways. The results give a functional effects and molecular mechanism insight, following LukS-PV treatment.

Soluble tau aggregates inhibit synaptic long-term depression and amyloid ß-facilitated LTD in vivo.

Soluble synaptotoxic aggregates of the main pathological proteins of Alzheimer's disease, amyloid ß-protein (Aß) and tau, have rapid and potent inhibitory effects on long-term potentiation (LTP). Although the promotion of synaptic weakening mechanisms, including long-term depression (LTD), is posited to mediate LTP inhibition by Aß, little is known regarding the action of exogenous tau on LTD. The present study examined the ability of different assemblies of full-length human tau to affect LTD in the dorsal hippocampus of the anaesthetized rat. Unlike Aß, intracerebroventricular injection of soluble aggregates of tau (SτAs), but not monomers or fibrils, potently increased the threshold for LTD induction in a manner that required cellular prion protein. However, MTEP, an antagonist of the putative prion protein coreceptor metabotropic glutamate receptor 5, did not prevent the disruption of synaptic plasticity by SτAs. In contrast, systemic treatment with Ro 25-6981, a selective antagonist at GluN2B subunit-containing NMDA receptors, reduced SτA-mediated inhibition of LTD, but not LTP. Intriguingly, SτAs completely blocked Aß-facilitated LTD, whereas a subthreshold dose of SτAs facilitated Aß-mediated inhibition of LTP. Overall, these findings support the importance of cellular prion protein in mediating a range of, sometimes opposing, actions of soluble Aß and tau aggregates with different effector mechanisms on synaptic plasticity.

NLRP3-dependent synaptic plasticity deficit in an Alzheimer's disease amyloidosis model in vivo.

Pro-inflammatory mechanisms have recently emerged as an important component of early Alzheimer's disease (AD) pathogenesis. A particularly attractive therapeutic strategy is to selectively prevent the disruptive effects of activation of the innate immune system in the brain at an early transitional stage by reducing the production or directly neutralizing pro-inflammatory cytokines, in particular IL-1ß and TNF-α. Here we tested their in vivo effects on synaptic plasticity deficits, which provide sensitive and robust measures of synaptic failure, in a rat model of AD amyloidosis. Using electrophysiological techniques we longitudinally studied the effects of the NLRP3 inflammasome inhibitor Mcc950, the IL-1 receptor antagonist (anakinra) and an anti-TNF-α agent (etanercept) in awake freely moving transgenic rats overexpressing AD associated ß-amyloid precursor protein at a pre-plaque stage of amyloidosis. Repeated treatment with Mcc950 reversibly abrogated the inhibition of long-term potentiation. The IL-1 receptor antagonist and etanercept also had a similar beneficial effect on the deficit in synaptic plasticity. Our findings support the clinical development of Mcc950 and clinically available IL-1- and TNF-α-neutralizing agents in early AD.

The current incidence, prevalence, and residual risk of hepatitis B viral infections among voluntary blood donors in China.

BACKGROUND: There are few data available on the prevalence, incidence, and residual risk of transfusion-transmitted HBV (TT-HBV) infections among Chinese blood donors. This study investigated the demographic characteristics of blood donors, as well as the prevalence, incidence, and residual risk (RR) of TT-HBV infections in six large blood centers in different regions of China. METHODS: The demographic characteristics and HBV screening test results of blood donors from six blood centers in different regions in China were collected and analyzed. The hepatitis B surface antigen (HBsAg) yield approach was used to estimate the incidence of HBV. Then, the RR of TT-HBV infections was evaluated using the incidence-window period model. RESULTS: The majority of donors were between 18 and 35 years old (including 35), with the exception of the Changzhi Blood Center where a majority of donors were between 35 and 55 years old (including 55). The prevalences of HBV were 0.13%, 0.078%, 0.16%, 0.07%, 0.20%, 0.25% in Hefei, Dalian, Changzhi, Kaifeng, Mianyang and Fujian, respectively. The estimated corresponding incidences were 213.44, 161.59, 989.80, 278.05, 125.31 and 352.19 per 105 person-years. Using an infectious window period of 59 days, the RR for HBV was estimated to be 34.14, 25.85, 158.35, 44.48, 20.04 and 56.35 per 105 person-years in Hefei, Dalian, Changzhi, Kaifeng, Mianyang and Fujian, respectively. CONCLUSION: Despite the introduction of more sensitive assays in blood screening, our data revealed that the current residual risk of TT-HBV infection was still high (overall 56.53 per 105 py). A continuous monitoring of the residual risk of transfusion-transmitted infections is crucial for safe blood management.

Switching off LTP: mGlu and NMDA receptor-dependent novelty exploration-induced depotentiation in the rat hippocampus.

Both electrically induced synaptic long-term potentiation (LTP) and long-term depression have been extensively studied as models of the cellular basis of learning and memory mechanisms. Recently, considerable interest has been generated by the possibility that the activity-dependent persistent reversal of previously established synaptic LTP (depotentiation) may play a role in the time- and state-dependent erasure of memory. Here, we examined the requirement for glutamate receptor activation in experience-induced reversal of previously established LTP in the CA1 area of the hippocampus of freely behaving rats. Continuous exploration of non-aversive novelty for ~30 min, which was associated with hippocampal activation as measured by increased theta power in the electroencephalogram, triggered a rapid and persistent reversal of high frequency stimulation-induced LTP both at apical and basal synapses. Blockade of metabotropic glutamate (mGlu) receptors with mGlu5 subtype-selective antagonists, or N-methyl-D-aspartate (NMDA) receptors with GluN2B subunit-selective antagonists, prevented novelty-induced depotentiation. These findings strongly indicate that activation of both mGlu5 receptors and GluN2B-containing NMDA receptors is required for experience-triggered induction of depotentiation at CA3-CA1 synapses. The mechanistic concordance of the present and previous studies of experience-induced and electrically induced synaptic depotentiation helps to integrate our understanding of the neurophysiological underpinnings of learning and memory.

Automated valvular heart disease detection using heart sound with a deep learning algorithm.

Background: Insufficient clinicians' auscultation ability delays the diagnosis and treatment of valvular heart disease (VHD); artificial intelligence provides a solution to compensate for the insufficiency in auscultation ability by distinguishing between heart murmurs and normal heart sounds. However, whether artificial intelligence can automatically diagnose VHD remains unknown. Our objective was to use deep learning to process and compare raw heart sound data to identify patients with VHD requiring intervention. Methods: Heart sounds from patients with VHD and healthy controls were collected using an electronic stethoscope. Echocardiographic findings were used as the gold standard for this study. According to the chronological order of enrollment, the early-enrolled samples were used to train the deep learning model, and the late-enrollment samples were used to validate the results. Results: The final study population comprised 499 patients (354 in the algorithm training group and 145 in the result validation group). The sensitivity, specificity, and accuracy of the deep-learning model for identifying various VHDs ranged from 71.4 to 100.0%, 83.5-100.0%, and 84.1-100.0%, respectively; the best diagnostic performance was observed for mitral stenosis, with a sensitivity of 100.0% (31.0-100.0%), a specificity of 100% (96.7-100.0%), and an accuracy of 100% (97.5-100.0%). Conclusions: Based on raw heart sound data, the deep learning model effectively identifies patients with various types of VHD who require intervention and assists in the screening, diagnosis, and follow-up of VHD.

Clinical Diagnostic Value of Serum 25-Hydroxyvitamin D in Severe Fever with Thrombocytopenia Syndrome.

Purpose: Severe Fever with Thrombocytopenia Syndrome (SFTS) is an infectious disease with rapid onset and high case fatality rate. The study was to explore the clinical value by examining the serum level of 25-hydroxyvitamin D (25 (OH) D) in SFTS patients. Methods: One hundred and five patients and 156 healthy controls were included. Univariate and multivariate regression analyses were performed to identify independent risk factors for disease progression. Subject operating characteristics (ROC) curves were drawn, and the corresponding area under the curve (AUC) was calculated to assess the sensitivity and specificity of the diagnostic disease. Results: The 25 (OH) D level of disease group was lower than that of healthy control group (22.12 (18.43, 25.86) ng/mL vs 27.36 (23.20, 32.71) ng/mL; P<0.05). The 25 (OH) D level of severe disease group was lower than that of mild disease group (20.55(16.30, 24.44) ng/mL vs 24.94(20.89, 31.91) ng/mL; P<0.05). And there was no significant difference of 25 (OH) D level between the survival group and death group in severe disease group. Multivariate Logistic regression analysis showed that the 25 (OH) D level under 19.665 ng/mL was an independent risk factor for the development of SFTS (OR = 0.901, P=0.040). Furthermore, age more than 68.5 years old and lactate dehydrogenase (LDH) more than 1023.5U/L were independent risk factors for death in severe patients with SFTS. Conclusion: Patients with SFTS have reduced 25 (OH) D level, and 25 (OH) D is a risk factor for disease severity in patients with SFTS. Vitamin D supplementation may be an effective measure to reduce the risk of infection and improve the prognosis.

Novel Biomarker Panel of Let-7d-5p and MiR-140-5p Can Distinguish Latent Tuberculosis Infection from Active Tuberculosis Patients.

Background: Mycobacterium tuberculosis (Mtb) survives inside a human host for a long time in the form of latent tuberculosis infection (LTBI). Latent infection of tuberculosis has the opportunity of developing into active tuberculosis (ATB), which has greatly endangered human health. The existing diagnostic methods cannot effectively distinguish LTBI from ATB. Therefore, more effective diagnostic biomarkers and methods are urgently needed. Methods: Here, we screened the GEO data set, conducted joint differential analysis and target gene enrichment analysis, after filtering the disease-related database, we screened the differential miRNA related to TB. The qPCR was used to verify the miRNAs in 84 serum samples. Different combinations of biomarkers were evaluated by logistic regression to obtain a biomarker panel with good performance for diagnosing LTBI. Results: A panel with two miRNAs (hsa-let-7d-5p, hsa-miR-140-5p) was established to differentiate LTBI from ATB. Receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) are 0.930 (sensitivity = 100%, specificity = 88.5%) and 0.923 (sensitivity = 100%, specificity = 92.3%) with the biomarker panel for the training set and test set respectively. Conclusion: The findings indicated that the logistic regression model built by let-7d-5p and miR-140-5p has the ability to distinguish LTBI from active TB patients.