Structural insights into immune escape at killer T cell epitope by SARS-CoV-2 Spike Y453F variants.

CD8+ T cell immunity, mediated by human leukocyte antigen (HLA) and T cell receptor (TCR), plays a critical role in conferring immune memory and protection against viral pathogens. The emergence of SARS-CoV-2 variants poses a serious challenge to the efficacy of current vaccines. Whereas numerous SARS-CoV-2 mutations associated with immune escape from CD8+ T cells have been documented, the molecular effects of most mutations on epitope-specific TCR recognition remain largely unexplored. Here, we studied an HLA-A24-restricted NYN epitope (Spike448-456) that elicits broad CD8+ T cell responses in COVID-19 patients characterized by a common TCR repertoire. Four natural mutations, N450K, L452Q, L452R, and Y453F, arose within the NYN epitope and have transmitted in certain viral lineages. Our findings indicate that these mutations have minimal impact on the epitope's presentation by cell surface HLA, yet they diminish the affinities of their respective peptide-HLA complexes (pHLAs) for NYN peptide-specific TCRs, particularly L452R and Y453F. Furthermore, we determined the crystal structure of HLA-A24 loaded with the Y453F peptide (NYNYLFRLF), and subsequently a ternary structure of the public TCRNYN-I complexed to the original NYN-HLA-A24 (NYNYLYRLF). Our structural analysis unveiled that despite competent presentation by HLA, the mutant Y453F peptide failed to establish a stable TCR-pHLA ternary complex due to reduced peptide: TCR contacts. This study supports the idea that cellular immunity restriction is an important driving force behind viral evolution.

Liver abscess and tracheal fistula induced by transcatheter arterial chemoembolization for hepatocellular carcinoma: A case report.

BACKGROUND: Transarterial chemoembolization (TACE) is a standard treatment for intermediate-stage hepatocellular carcinoma (HCC). The complications of TACE include biliary tract infection, liver dysfunction, tumor lysis syndrome, biloma, partial intestinal obstruction, cerebral lipiodol embolism, etc. There are few reports about tracheal fistula induced by TACE. CASE SUMMARY: A 42-year-old man came to our hospital with cough and expectoration for 1 month after TACE for HCC. Laboratory test results showed abnormalities of albumin, hemoglobin, prothrombin time, C-reactive protein, D-dimer, and prothrombin. Culture of both phlegm and liver pus revealed growth of Citrobacter flavescens. Computed tomography showed infection in the inferior lobe of the right lung and a low-density lesion with gas in the right liver. Liver ultrasound showed that there was a big hypoechoic liquid lesion without blood flow signal. Drainage for liver abscess by needle puncture under ultrasonic guidance was performed. After 1 month of drainage and anti-infection therapy, the abscess in the liver and the infection in the lung were reduced obviously, and the symptom of expectoration was relieved. CONCLUSION: Clinicians should be alert to the possibility of complications of liver abscess and tracheal fistula after TACE for HCC. Drainage for liver abscess by needle puncture under ultrasonic guidance could relieve the liver abscess and tracheal fistula.

Trends in population attributable fraction of modifiable risk factors for cardiovascular diseases across three decades.

AIM: To evaluate temporal trends, across three decades, in the population attributable fractions (PAFs) of modifiable risk factors for 5-year risk of cardiovascular diseases (CVDs). METHODS: Within population-based Rotterdam Study, we defined three time-groups of individuals without established CVD at 'baseline' with a mean age of 70 years, and followed for five years: Epoch 1990s (1989-1993, N=6195), Epoch 2000s (1997-2001, N=5572) and Epoch 2010s (2009-2014, N=5135). The prevalence of risk factors and related relative risks were combined to quantify PAFs. RESULTS: The PAF of the six risk factors combined for global CVD was 0.57 (95% confidence interval [CI] 0.47 to 0.65), 0.52 (0.39 to 0.62) and 0.39 (0.18 to 0.54) in three respective epochs. Hypertension contributed the highest PAF to global CVD in Epoch 1990s (0.37, 95% CI: 0.28 to 0.44) and 2000s (0.34, 95% CI: 0.22 to 0.43), while smoking was the largest contributor in Epoch 2010s (0.20, 95% CI: 0.06 to 0.32). Dyslipidemia changed population-level coronary heart disease risk over time. For stroke, hypertension became a less significant contributor over time, but smoking became a larger contributor. For heart failure, all risk factors showed non-significant PAFs in Epoch 2010s. PAFs related to individual risk factor varied among women and men. CONCLUSION: Six modifiable risk factors to population-level global CVD risk decreased over time, but still explained 39% of total CVD in the latest decade. PAFs changed considerably for hypertension, dyslipidemia, and smoking. Risk factors had different PAFs for different CVDs with pronounced sex differences.

The contribution of the individual cardiovascular risk factors to population CVD risk considerably changed over the past 3 decades, especially for hypertension, dyslipidemia, and smoking. Traditional modifiable risk factors exerted declining contributions to population burden of total CVD over the past three decades, suggesting good progress in CVD prevention. Nonetheless, in the latest decade, unfavorable risk factors accounted for 39% of total CVD burden. Sex differences in the contributions of abdominal obesity, diabetes and smoking to cardiovascular outcomes were observed.

Cascade CRISPR/Cas12a and DSN for the electrochemical biosensing of miR-1246 in BC-derived exosomes.

MiR-1246 in breast cancer-derived exosomes was a promising biomarker for early diagnosis of breast cancer(BC). However, the low abundance, high homology and complex background interference make the accurate quantitative detection of miR-1246 facing great challenges. In this study, we developed an electrochemical biosensor based on the subtly combined of CRISPR/Cas12a, double-stranded specific nuclease(DSN) and magnetic nanoparticles(MNPs) for the detection of miR-1246 in BC-derived exosomes. Ascribed to the good synergistic effect of DSN, Cas12a and MNPs, the developed electrochemical biosensor exhibited excellent performance with the linear range from 500 aM to 5 pM, and the detection limit as low down to about 50 aM. The target-specific triggered enzyme-digest activity of DSN and Cas12a system, as well as the powerful separation ability of MNPs ensure the high specificity of developed electrochemical biosensor which can distinguish single base mismatches. In addition, the developed electrochemical biosensor has been successfully applied to detect miR-1246 in blood-derived exosomes and realize distinguishing the BC patients from the healthy individuals. It is expected that the well-designed biosensing platform will open up new avenues for clinical liquid biopsy and early screening of breast cancer, as well as provide deeper insights into clinical oncology treatment.

A 14-Bit Hybrid Analog-to-Digital Converter for Infrared Focal Plane Array Digital Readout Integrated Circuit.

This paper presents a 14-bit hybrid column-parallel compact analog-to-digital converter (ADC) for the application of digital infrared focal plane arrays (IRFPAs) with compromised power and speed performance. The proposed hybrid ADC works in two phases: in the first phase, a 7-bit successive approximation register (SAR) ADC performs coarse quantization; in the second phase, a 7-bit single-slope (SS) ADC performs fine quantization to complete the residue voltage conversion. In this work, the number of unit capacitors is reduced to 1/128th of that of a conventional 14-bit SAR ADC, which is beneficial for the application of small pixel-pitch IRFPAs. In this work, a tradeoff segmented thermometer-coded digital-to-analog converter (DAC) is adopted in the first 7-bit coarse quantization process: the lower 3-bit is binary coded, and the upper 4-bit is thermometer coded. A thermometer-coded DAC can improve the linearity of ADC. Capacitor array matching can be incredibly relaxed compared with a binary-weight 14-bit SAR ADC, resulting in a noncalibration feature. Moreover, by sharing DAC and comparator analog circuits between the SAR ADC and the SS ADC, the power consumption and layout area are consequently reduced. The proposed hybrid ADC was fabricated using a 180 nm CMOS process. The measurement results show that the proposed ADC has a differential nonlinearity of -0.61/+0.84 LSB and a sampling rate of 120 kS/s. The developed ADC achieves a temporal noise of 1.7 LSBrms at a temperature of 77 K. In addition, the SNDR is 72.9 dB, and the ENOB is 11.82 bit, respectively. Total power consumption is 71 µW from supply voltages of 3.3 V (analog) and 1.8 V (digital).

Achieving a solar-to-chemical efficiency of 3.6% in ambient conditions by inhibiting interlayer charges transport.

Efficiently converting solar energy into chemical energy remains a formidable challenge in artificial photosynthetic systems. To date, rarely has an artificial photosynthetic system operating in the open air surpassed the highest solar-to-biomass conversion efficiency (1%) observed in plants. In this study, we present a three-dimension polymeric photocatalyst achieving a solar-to-H2O2 conversion efficiency of 3.6% under ambient conditions, including real water, open air, and room temperature. The impressive performance is attributed to the efficient storage of electrons inside materials via expeditious intramolecular charge transfer, and the fast extraction of the stored electrons by O2 that can diffuse into the internal pores of the self-supporting three-dimensional material. This construction strategy suppresses the interlayer transfer of excitons, polarizers and carriers, effectively increases the utilization of internal excitons to 82%. This breakthrough provides a perspective to substantially enhance photocatalytic performance and bear substantial implications for sustainable energy generation and environmental remediation.

Lactobacillus acidophilus protects against Corynebacterium pseudotuberculosis infection by regulating the autophagy of macrophages and maintaining gut microbiota homeostasis in C57BL/6 mice.

Corynebacterium pseudotuberculosis (C. p), a facultative intracellular bacterium, is an important zoonotic pathogen that causes abscesses and pyogenic granulomas. The relationship between gut microbiota and host health or diseases has received increasing attention. However, the role of gut microbiota in the process of C. p infection is still unclear. In this study, we established a C. p infection model in C57BL/6 mice and examined the impact of preemptive oral administration Lactobacillus acidophilus (L. acidophilus) on infection. Our findings revealed that C. p infection led to pronounced pathological alterations in the liver and kidneys, characterized by abscess formation, intense inflammatory responses, and bacterial overload. Remarkably, these deleterious effects were greatly relieved by oral administration of L. acidophilus before infection with C. p. Additionally, we further found that during C. p infection, peritoneal macrophages (PMs) of mice orally administered with L. acidophilus accumulated more rapidly at sites of infection. Furthermore, our results showed that PMs from mice with oral L. acidophilus administration showed a stronger C. p clearance effect, and this was mediated by high expression of LC3-II protein. Meanwhile, oral administration of L. acidophilus protected the gut microbiota disorder in C57BL/6 mice caused by C. p infection. In summary, our study demonstrates that oral administration of L. acidophilus confers effective protection against C. p infection in C57BL/6 mice by modulating macrophage autophagy, thereby augmenting bacterial clearance and preserving gut microbiota and function stability. These findings position L. acidophilus as a viable probiotic candidate for the clinical prevention of C. p infection. IMPORTANCE: Corynebacterium pseudotuberculosis (C. p) is known to induce a range of chronic diseases in both animals and humans. Currently, clinical treatment for C. p infection mainly relies on antibiotic therapy or surgical intervention. However, excessive use of antibiotics may increase the risk of drug-resistant strains, and the effectiveness of treatment remains unsatisfactory. Furthermore, surgical procedures do not completely eradicate pathogens and can easily cause environmental pollution. Probiotic interventions are receiving increasing attention for improving the body's immune system and maintaining health. In this study, we established a C. p infection model in C57BL/6 mice to explore the impact of Lactobacillus acidophilus during C. p infection. Our results showed that L. acidophilus effectively protected against C. p infection by regulating the autophagy of macrophages and maintaining intestinal microbiota homeostasis. This study may provide a new strategy for the prevention of C. p infection.

A Synergetic Pore Compartmentalization and Hydrophobization Strategy for Synchronously Boosting the Stability and Activity of Enzyme.

Spatial immobilization of fragile enzymes using a nanocarrier is an efficient means to design heterogeneous biocatalysts, presenting superior stability and recyclability to pristine enzymes. An immobilized enzyme, however, usually compromises its catalytic activity because of inevasible mass transfer issues and the unfavorable conformation changes in a confined environment. Here, we describe a synergetic metal-organic framework pore-engineering strategy to trap lipase (an important hydrolase), which confers lipase-boosted stability and activity simultaneously. The hierarchically porous NU-1003, featuring interconnected mesopore and micropore channels, is precisely modified by chain-adjustable fatty acids on its mesopore channel, into which lipase is trapped. The interconnected pore structure ensures efficient communication between trapped lipase and exterior media, while the fatty acid-mediated hydrophobic pore can activate the opening conformation of lipase by interfacial interaction. Such dual pore compartmentalization and hydrophobization activation effects render the catalytic center of trapped lipase highly accessible, resulting in 1.57-fold and 2.46-fold activities as native lipase on ester hydrolysis and enantioselective catalysis. In addition, the feasibility of these heterogeneous biocatalysts for kinetic resolution of enantiomer is also validated, showing much higher efficiency than native lipase.

Identifying Factors Affecting the Survival of Patients with HIV-Associated B-Cell Lymphoma Using a Random Survival Forest Model.

Background: There have been no reports about the application of random survival forest (RSF) model to predict disease progression of HIV-associated B-cell lymphoma. Methods: A total of 44 patients with HIV-associated B-cell lymphoma who were referred to Nanjing Second Hospital from 2012 to 2019 were included. The RSF model was used to find predictors of survival, and the results of the RSF model were compared with those of the Cox model. The data were analyzed using R software (version 4.1.1). Results: One-, 2-, and 3-year survival rates were 74.5%, 57.7%, and 48.6%, respectively, and the median survival was 59.0 months. The first 3 most important predictors of survival included lactate dehydrogenase (LDH), absolute monocyte count (AMC), and white blood cells (WBCs) count. The median survival of high-risk patients was only 4.0 months. Areas under the curve (AUCs) of the RSF model remained at more than 0.90 at 1, 2, and 3 years. The RSF model displayed a lower prediction error rate (21.9%) than the Cox model (25.4%). Conclusions: Lactate dehydrogenase, AMC, and WBCs count are the most important prognostic predictors for patients with HIV-associated B-cell lymphoma. Much larger prospective and/or multicentre studies are required to validtae this RSF model.

[Clinical Characteristics and Prognosis of Patients with Acute Leukemia Complicated with Mucormycosis after Chemotherapy].

OBJECTIVE: To analyze the characteristics and prognosis of patients with mucormycosis after chemotherapy for acute leukemia, and to strengthen understanding of the disease. METHODS: 7 cases of acute leukemia (AL) patients diagnosed with mucormycosis by metagenomic next generation sequencing (mNGS) after chemotherapy at the First Affiliated Hospital of Bengbu Medical College from October 2021 to June 2022 were collected, and their clinical data, including clinical characteristics, diagnosis, treatment, and prognosis, were retrospectively analyzed. RESULTS: Among the 7 patients with AL complicated with mucormycosis, there were 3 males and 4 females, with a median age of 52(20-59) years. There were 6 cases of acute myeloid leukemia (AML) and 1 case of acute lymphocytic leukemia (ALL). Extrapulmonary involvement in 4 cases, including 1 case suspected of central nervous system involvement. The median time for the occurrence of mucor infection was 16(6-69) days after chemotherapy and 19(14-154) days after agranulocytosis. The main clinical manifestations of mucormycosis were fever (7/7), cough (3/7), chest pain (3/7) and dyspnea (1/7). The most common chest CT imaging findings were nodules, patchy or mass consolidation (6/7). All patients were treated with posaconazole or voriconazole prophylaxis during neutropenia phase. 5 patients died within 8 months, and the median time from diagnosis to death was 1 month. CONCLUSION: Although prophylactic antifungal therapy is adopted, patients with acute leukemia still have a risk of mucor infection during the neutropenia phase. Fever is the main manifestation in the early stage of mucor infection. The use of intravenous antifungal drugs alone is ineffective and there is a high mortality rate in acute leukemia patients with mucormycosis.

Morphology Control of Zr-Based Luminescent Metal-Organic Frameworks for Aflatoxin B1 Detection.

Metal-organic frameworks (MOFs) have gained significant prominence as sensing materials owing to their unique properties. However, understanding the correlation between the morphology, properties, and sensing performance in these MOF-based sensors remains a challenge, limiting their applications and potential for improvement. In this study, Zr-MOF was chosen as an ideal model to explore the impact of the MOF morphology on the sensing performance, given its remarkable stability and structural variability. Three luminescent MOFs (namely rod-like Zr-LMOF, prismoid-like Zr-LMOF, and ellipsoid-like Zr-LMOF) were synthesized by adjusting the quantities of the benzoic acid and the reaction time. More importantly, the sensing performance of these Zr-LMOFs in response to aflatoxin B1 (AFB1) was thoroughly examined. Notably, the ellipsoid-like Zr-LMOF exhibited significantly higher sensitivity compared to other Zr-LMOFs, attributed to its large specific surface area and pore volume. Additionally, an in-depth investigation into the detection mechanism of AFB1 by Zr-LMOFs was conducted. Building upon these insights, a ratiometric fluorescence sensor was developed by coordinating Eu3+ with ellipsoid-like Zr-LMOF, achieving a remarkably lower detection limit of 2.82 nM for AFB1. This study contributes to an improved comprehension of the relationship between the MOF morphology and the sensing characteristics while presenting an effective approach for AFB1 detection.

Endoscopic Ultrasound-Guided Fine Needle Aspiration has High Diagnostic Value in the Diagnosis of Solid Pancreatic Lesions.

Objective: To analyze the potential factors influencing the diagnostic capability of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and provide medication treatment recommendations for patients with pancreatic solid mass lesions. Methods: A retrospective analysis was conducted on clinical data of 92 patients with pancreatic solid mass lesions who underwent EUS-FNA examination after detection by imaging studies. The diagnostic effectiveness of EUS-FNA was evaluated based on cytological or histological examination results. Logistic regression analysis was subsequently performed to analyze the potential factors influencing the diagnostic capability of EUS-FNA in patients with pancreatic solid mass lesions. Results: EUS-FNA was successfully performed in all 92 patients, with a puncture success rate of 100.00%. Only one patient experienced transient hyperamylasemia, which resolved with conservative treatment. No other serious complications were observed. Among the 92 patients, 70 patients obtained a definite diagnosis after EUS-FNA (Group A), while 22 patients did not achieve a definite diagnosis (Group B) after the procedure. Univariate analysis showed that lesion size, dilation of the pancreatic duct or bile duct, negative pressure, and suction method were significantly different between Group A and Group B (P < .05). Multivariate logistic regression analysis revealed that lesion size, dilation of the pancreatic duct or bile duct, negative pressure, and suction method were potential factors influencing the diagnostic ability of EUS-FNA in patients with solid pancreatic lesions (P < .05). Conclusion: EUS-FNA has a high diagnostic value in the evaluation of solid pancreatic lesions. Lesion size, dilation of the pancreatic duct or bile duct, negative pressure, and suction method are potential factors influencing the diagnostic ability of EUS-FNA in patients with solid pancreatic lesions. In terms of medical treatment, specific treatment methods and drug choices should be based on a comprehensive evaluation of the nature of the patient's lesions and the severity of the condition.

Penicillin Allergy Testing and Delabeling for Patients Who Are Prescribed Penicillin: A Systematic Review for a World Health Organization Guideline.

Secondary prevention with penicillin aims to prevent further episodes of acute rheumatic fever and subsequent development of rheumatic heart disease (RHD). Penicillin allergy, self-reported by 10% of the population, can affect secondary prevention programs. We aimed to assess the role for (i) routine penicillin allergy testing and the (ii) safety of penicillin allergy delabeling approaches in this context. We searched MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, WHO ICTRP, ISRCTN, and CPCI-S to identify the relevant reports. We found 2419 records, but no studies addressed our initial question. Following advice from the WHO-Guideline committee and experts, we identified 6 manuscripts on allergy testing focusing on other populations showing that the prevalence of allergy confirmed by testing was low and the incidence of life-threatening reactions to BPG was very low (< 1-3/1000 individuals treated). A subsequent search addressed penicillin allergy delabeling. This found 516 records, and 5 studies addressing the safety of direct oral drug challenge vs. skin testing followed by drug administration in patients with suspected penicillin allergy. Immediate allergic reactions of minor severity were observed for a minority of patients and occurred less frequently in the direct drug challenge group: 2.3% vs. 11.5%; RR = 0.25, 95%CI 0.15-0.45, P < 0.00001, I2 = 0%. No anaphylaxis or deaths were observed. Severe allergic reactions to penicillin are extremely rare and can be recognized and dealt by trained healthcare workers. Confirmation of penicillin allergy diagnosis or delabeling using direct oral drug challenge or penicillin skin testing seems to be safe and is associated with a low rate of adverse reactions.

Oxygen-Centered Organic Radicals-Involved Unified Heterogeneous Self-Fenton Process for Stable Mineralization of Micropollutants in Water.

Removing organic micropollutants from water through photocatalysis is hindered by catalyst instability and substantial residuals from incomplete mineralization. Here, a novel water treatment paradigm, the unified heterogeneous self-Fenton process (UHSFP), which achieved an impressive 32% photon utilization efficiency at 470 nm, and a significant 94% mineralization of organic micropollutants-all without the continual addition of oxidants and iron ions is presented. In UHSFP, the active species differs fundamentally from traditional photocatalytic processes. One electron acceptor unit of photocatalyst acquires only one photogenerated electron to convert into oxygen-centered organic radical (OCOR), then spontaneously completing subsequent processes, including pollutant degradation, hydrogen peroxide generation, activation, and mineralization of organic micropollutants. By bolstering electron-transfer capabilities and diminishing catalyst affinity for oxygen in the photocatalytic process, the generation of superoxide radicals is effectively suppressed, preventing detrimental attacks on the catalyst. This study introduces an innovative and cost-effective strategy for the efficient and stable mineralization of organic micropollutants, eliminating the necessity for continuous chemical inputs, providing a new perspective on water treatment technologies.

Establishment of in-hospital nutrition support program for middle-aged and elderly patients with acute decompendated heart failure.

OBJECTIVE: To construct a nutrition support program for middle-aged and elderly patients with acute decompensated heart failure (ADHF) during hospitalization. METHODS: Based on the JBI Evidence-Based Health Care Model as the theoretical framework, the best evidence was extracted through literature analysis and a preliminary nutrition support plan for middle-aged and elderly ADHF patients during hospitalization was formed. Two rounds of expert opinion consultation were conducted using the Delphi method. The indicators were modified, supplemented and reduced according to the expert's scoring and feedback, and the expert scoring was calculated. RESULTS: The response rates of the experts in the two rounds of consultation were 86.7% and 100%, respectively, and the coefficient of variation (CV) for each round was between 0.00% and 29.67% (all < 0.25). In the first round of expert consultation, 4 items were modified, 3 items were deleted, and 3 items were added. In the second round of the expert consultation, one item was deleted and one item was modified. Through two rounds of expert consultation, expert consensus was reached and a nutrition support plan for ADHF patients was finally formed, including 4 first-level indicators, 7 s-level indicators, and 24 third-level indicators. CONCLUSION: The nutrition support program constructed in this study for middle-aged and elderly ADHF patients during hospitalization is authoritative, scientific and practical, and provides a theoretical basis for clinical development of nutrition support program for middle-aged and elderly ADHF patients during hospitalization.

A meta-analysis of antibiotic residues in the Beibu Gulf.

Antibiotic residue stands as a significant ongoing environmental issue, with aquaculture being a major source of annual antibiotic discharge into the ocean. Nevertheless, there is still an incomplete evaluation of antibiotic residues in the Beibu Gulf, an area encompassed by two prominent aquaculture nations, China and Vietnam. The present systematic review and meta-analysis was conducted to examine the presence antibiotic residues in the Beibu Gulf based on published studies. Data were obtained through eight databases up to December 19th, 2023, and were updated on April 15th, 2024. The pooled concentration of antibiotic residues in seawater was 5.90 (ng/L), ranging from 5.73 to 6.06 (ng/L), and was 8.03 (ng/g), ranging from 7.77 to 8.28 (ng/g) in sediments. Fluoroquinolones, tetracyclines, and macrolides were identified as the main antibiotics found in both seawater and sediment samples. The Beibu Gulf showed higher antibiotic levels in its western and northeastern areas. Additionally, the nearshore mangrove areas displayed the highest prevalence of antibiotic residues. It is strongly advised to conduct regular long-term monitoring of antibiotic residues in the Beibu Gulf. Collaborative surveys covering the entire Beibu Gulf involving China and Vietnam are recommended.

Handheld echocardiography for the screening and diagnosis of rheumatic heart disease: a systematic review to inform WHO guidelines.

BACKGROUND: Early detection and diagnosis of acute rheumatic fever and rheumatic heart disease are key to preventing progression, and echocardiography has an important diagnostic role. Standard echocardiography might not be feasible in high-prevalence regions due to its high cost, complexity, and time requirement. Handheld echocardiography might be an easy-to-use, low-cost alternative, but its performance in screening for and diagnosing acute rheumatic fever and rheumatic heart disease needs further investigation. METHODS: In this systematic review and meta-analysis, we searched Embase, MEDLINE, LILACS, and Conference Proceedings Citation Index-Science up to Feb 9, 2024, for studies on the screening and diagnosis of acute rheumatic fever and rheumatic heart disease using handheld echocardiography (index test) or standard echocardiography or auscultation (reference tests) in high-prevalence areas. We included all studies with useable data in which the diagnostic performance of the index test was assessed against a reference test. Data on test accuracy in diagnosing rheumatic heart disease, acute rheumatic fever, or carditis with acute rheumatic fever (primary outcomes) were extracted from published articles or calculated, with authors contacted as necessary. Quality of evidence was appraised using GRADE and QUADAS-2 criteria. We summarised diagnostic accuracy statistics (including sensitivity and specificity) and estimated 95% CIs using a bivariate random-effects model (or univariate random-effects models for analyses including three or fewer studies). Area under the curve (AUC) was calculated from summary receiver operating characteristic curves. Heterogeneity was assessed by visual inspection of plots. This study was registered with PROSPERO (CRD42022344081). FINDINGS: Out of 4868 records we identified 11 studies, and two additional reports, comprising 15 578 unique participants. Pooled data showed that handheld echocardiography had high sensitivity (0·87 [95% CI 0·76-0·93]), specificity (0·98 [0·71-1·00]), and overall high accuracy (AUC 0·94 [0·84-1·00]) for diagnosing rheumatic heart disease when compared with standard echocardiography (two studies; moderate certainty of evidence), with better performance for diagnosing definite compared with borderline rheumatic heart disease. High sensitivity (0·79 [0·73-0·84]), specificity (0·85 [0·80-0·89]), and overall accuracy (AUC 0·90 [0·85-0·94]) for screening rheumatic heart disease was observed when pooling data of handheld echocardiography versus standard echocardiography (seven studies; high certainty of evidence). Most studies had a low risk of bias overall. Some heterogeneity was observed for sensitivity and specificity across studies, possibly driven by differences in the prevalence and severity of rheumatic heart disease, and level of training or expertise of non-expert operators. INTERPRETATION: Handheld echocardiography has a high accuracy and diagnostic performance when compared with standard echocardiography for diagnosing and screening of rheumatic heart disease in high-prevalence areas. FUNDING: World Health Organization. TRANSLATIONS: For the Chinese, French, Italian, Persian, Portuguese, Spanish and Urdu translations of the abstract see Supplementary Materials section.

Characterization and epidemiologic analysis of mycoplasmal pneumonia of sheep in Qinghai Province.

Mycoplasmal pneumonia in sheep and goats usually result covert but huge economic losses in the sheep and goat industry. The disease is prevalent in various countries in Africa and Asia. Clinical manifestations in affected animals include anorexia, fever, and respiratory symptoms such as dyspnea, polypnea, cough, and nasal discharge. Due to similarities with other respiratory infections, accurate diagnosis can be challenging, and isolating the causative organism is often problematic. However, the utilization of molecular techniques, such as PCR, allows for rapid and specific identification of pathogens. Thus, a goat infection model with Mycoplasma was established and the pathogen was tested using PCR. The results indicated that this approach could be effectively utilized for the rapid detection of mycoplasma in clinical settings. Additionally, the prevalence of contagious pleuropneumonia of sheep in Qinghai Province was further investigated through PCR analysis. A total of 340 nasal swabs were collected from 17 sheep farms in Qinghai province. Among these samples, 84 tested positive for Mycoplasma mycoides subsp. capri (Mmc) and 148 tested positive for Mycoplasma ovipneumoniae (Movi), resulting in positive rates of 24.71% and 43.53% respectively. Furthermore, our investigation revealed positive PCR results for nasal swabs, trachea, and lung samples obtained from sheep exhibiting symptoms suggestive of mycoplasma infection. Moreover, three distinct strains were isolated from these positive samples. Additionally, the inflammatory cytokines of peripheral blood mononuclear cells (PBMCs) were assessed using RT-PCR. The findings demonstrated a high susceptibility of sheep to Movi in Qinghai province, with infected sheep displaying an inflammatory response. Consequently, the outcomes of this study will furnish valuable epidemiological insights for the effective prevention and control of this disease within Qinghai Province.

Biomarker Potential of LINC00313 in Head and Neck Squamous Cell Carcinoma: Correlation with Epithelial-Mesenchymal Transition and Immune Cell Infiltration.

Although LINC00313 is dysregulated in several tumors, its role in head and neck squamous cell carcinoma (HNSC) is not fully understood. The aim of this study was to analyze the role of LINC00313 in HNSC. The clinical information and LINC00313 expression data of HNSC were mined from the TCGA/GEO/cbioportal database. The correlation between LINC00313 expression and immune cell infiltration in HNSC tumors was analyzed by bioinformatics and gene enrichment analysis was performed. LINC00313 was silenced in HNSC cell lines, and changes at the genetic and molecular levels were verified through qRT-PCR and Western blotting. The researchers also validated its functional phenotype through a series of cell function experiments. The results showed that overexpression and copy number variation of LINC00313 in HNSC were associated with poorer prognosis. In addition, LINC00313 expression was significantly negatively correlated with immune cell infiltration. Silencing of LINC00313 in HNSC cells significantly reduced the rate of cell migration. LINC00313 may affect the progression of HNSC by regulating epithelial-mesenchymal transition. In conclusion, LINC00313 is a potential biomarker of HNSC prognosis and a potential target for immunotherapy.