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.

Head and Neck Osteosarcoma: Perineural Invasion is Associated With Disease-Free Survival and Tumor Metastasis.

BACKGROUND: Head and neck osteosarcoma (HNOS) is the most common bone malignancy in the head and neck region, accounting for 10% of all osteosarcoma cases. Perineural invasion (PNI) is a notable indication of aggressive tumor behavior, which includes the phenomenon of tumor cells invading any of the 3 layers of the nerve sheath or tumor cells gathering, encircling one-third of the nerve circumference, and infiltrating and metastasizing along the nerve. PNI has been reported in various malignant tumors and is considered to be linked to poor prognosis. PURPOSE: The study's purpose is to measure the association between PNI and survival outcomes in patients with HNOS. STUDY DESIGN, SETTING, SAMPLE: This retrospective cohort study focused on HNOS patients who underwent surgery at the Department of Oral and Maxillofacial Head and Neck Oncology, Shanghai Ninth People's Hospital School of Medicine, Shanghai Jiao Tong University, from January 1, 2019 to December 31, 2021. Patients who did not undergo complete surgical resection of the tumor, did not receive a conventional osteosarcoma diagnosis, and had positive surgical margins were eliminated. PREDICTOR VARIABLE: The predictor variable is PNI status. The pathological section of the tumor was consistent with any of the PNI features, which was considered PNI-positive. MAIN OUTCOME VARIABLE(S): The primary outcome variables were 3-year disease-free survival (DFS) and 3-year overall survival. Secondary outcomes were 3-year tumor local recurrence and 3-year metastasis (MT). COVARIATES: Covariates were categorized into the following categories: demographic variables (age, sex), clinical variables (tumor region, primary tumor), and treatment variables (chemotherapy, radiotherapy). ANALYSES: Analytic statistical methods were used for the data analysis. Pearson χ2 or Fisher's exact test was used to describe the baseline data. Kaplan-Meier is used to calculate survival rates. The Cox regression model was adapted for univariate and multivariate analysis. A P value less than .05 indicated statistical significance. RESULTS: The study sample comprised 70 patients; 33 (47.1%) were male, and the mean age was 42.2 (standard deviation: 16.7) years. There were 15 (21.4%) cases of PNI. The 3-year DSF rate and OS rate were 67.3% and 82.0%, respectively. PNI-positive resulted in higher risk for MT (P ＜ .01, hazard ratio: 5.95, 95% confidence interval: 1.62-21.86) and negative impact on DFS (P < .01, hazard ratio: 6.35, 95% confidence interval: 2.11-19.17) for HNOS patients. CONCLUSION AND RELEVANCE: Positive PNI status was associated with decreased DFS and increased risk of MT.

Prognostic factors and outcomes of invasive pulmonary aspergillosis, a retrospective hospital-based study.

Objective: Invasive pulmonary aspergillosis (IPA) affects immunocompromised hosts and is associated with higher risks of respiratory failure and mortality. However, the clinical outcomes of different IPA types have not been identified. Methods: Between September 2002 and May 2021, we retrospectively enrolled patients with IPA in Taichung Veterans General Hospital, Taiwan. Cases were classified as possible IPA, probable IPA, proven IPA, and putative IPA according to EORTC/MSGERC criteria and the AspICU algorithm. Risk factors of respiratory failure, kidney failure, and mortality were analyzed by logistic regression. A total of 3-year survival was assessed by the Kaplan-Meier method with log-rank test for post-hoc comparisons. Results: We included 125 IPA patients (50: possible IPA, 47: probable IPA, 11: proven IPA, and 17: putative IPA). Comorbidities of liver cirrhosis and solid organ malignancy were risk factors for respiratory failure; diabetes mellitus and post-liver or kidney transplantation were related to kidney failure. Higher galactomannan (GM) test optical density index (ODI) in either serum or bronchoalveolar lavage fluid was associated with dismal outcomes. Probable IPA and putative IPA had lower 3-year respiratory failure-free survival compared to possible IPA. Probable IPA and putative IPA exhibited lower 3-year renal failure-free survival in comparison to possible IPA and proven IPA. Putative IPA had the lowest 3-year overall survival rates among the four IPA groups. Conclusion: Patients with putative IPA had higher mortality rates than the possible, probable, or proven IPA groups. Therefore, a prompt diagnosis and timely treatment are warranted for patients with putative IPA.

Head and Neck Soft Tissue Sarcoma Patient: Age and Tumor Region Are Predictive in Disease-Free Survival and Overall Survival.

BACKGROUND: Head and neck soft tissue sarcoma (HNSTS), rare and heterogeneous malignancies, are treated primarily treated with surgery. However, prognostic indicators that might guide HNSTS management are poorly defined. PURPOSE: Main purpose of this study is to find variables linked to HNSTS patients' prognosis. Assessment of the Tumor, Node, Metastatis (TNM) system is the secondary purpose. STUDY DESIGN, SETTING, SAMPLE: This study is a retrospective cohort performed on HNSTS patients who received surgery at the Department of Oral and Maxillofacial Head and Neck Oncology, Shanghai Ninth People's Hospital School of Medicine, Shanghai Jiao Tong University from January 1, 2006, to December 31, 2014. Strict inclusion criteria were applied. PREDICTOR VARIABLE: The predictor variable was a set of heterogenous risk factors and were grouped into the following categories: demographic (age and gender), clinical (primary tumor, tumor region, tumor size, and TNM stage), and treatment (surgical margin, treatment therapy). MAIN OUTCOME VARIABLE(S): The primary outcome variables were time to 5-year disease-free survival (DFS) and 5-year overall survival (OS). The secondary outcome variables were time to 5-year tumor local recurrence and metastasis. COVARIATES: Not applicable. ANALYSES: Descriptive statistical analysis was carried out. Pearson χ2 test was employed in univariate analysis. Cox regression was modified for multiple variable analysis with components that had significant P values in univariate analysis or variables with potential prognostic value. Log-rank test was applied to compare survival situations under various variables. P value less than .05 was statistically significant. RESULTS: The sample was composed of 100 subjects with a mean age of 43.47 (standard deviation: 16.15) years old and 56 (56%) were male. The 5-year DSF and OS were 59 and 60%, respectively. Variables associated with poor DFS and OS were age > 60 years (P = .003, hazard ratio [HR]: 4.95, 95% confidence interval [CI]: 1.71,14.1; P = .005, HR: 4.48, 95% CI: 1.57,12.8) and non-primary tumors (P＜.001, HR: 8.41, 95% CI: 2.85,24.8; P = .002, HR: 6.90, 95% CI: 2.46,19.4), respectively. Maxilla and skull base cancers had local recurrence (12/18, 66.7%) more common. T2 (TNM) tumor displayed higher tendency in DFS(P = .009, HR: 4.20, 95% CI: 1.42,12.4) and metastasis(P = .09, HR: 3.51, 95% CI: 0.82,15.0) than T1 (TNM) tumors. CONCLUSION AND RELEVANCE: Poor prognosis is associated with maxilla and skull base tumors as well as patients over 60 years. TNM stage appeared to have limited prognostic significance.

Modular Synthesis of Improbable Rotaxanes with All-Benzene Scaffolds.

"Improbable" rotaxanes consisting of interlocked conjugated components represent non-trivial synthetic targets, not to mention those with all-benzene scaffolds. Herein, a modular synthetic strategy has been established using an isolable azo-linked pre-rotaxane as the core module, in which the azo group functions as a tracelessly removable template to direct mechanical bond formations. Through versatile connections of the pre-rotaxane and other customizable modules, [2]- and [3]rotaxanes derived from all-benzene scaffolds have been accomplished, demonstrating the utility and potential of the synthetic design for all-benzene interlocked supramolecules.

A Potent SOS1 PROTAC Degrader with Synergistic Efficacy in Combination with KRASG12C Inhibitor.

AMG510, as the first approved inhibitor for KRASG12C mutation, has shown promising efficacy in nonsmall-cell lung cancer and colorectal cancer harboring KRASG12C mutation. However, the moderate response rate and the rapid emergence of acquired resistance limit the therapeutic potential of AMG510, highlighting the need for the development of combination strategies. Here, we observed the suppression of RAS-MAPK signaling induced by AMG510 was prolonged and enhanced by SOS1 knockdown. Thus, we design, synthesize, and characterize a potent and specific SOS1 degrader 23. Compound 23 showed efficient SOS1 degradation in KRAS-driven cancer cells and achieved significant antiproliferative potency. Importantly, the combination of 23 with AMG510 suppressed RAS signaling feedback activation, showing synergistic effects against KRASG12C mutant cells in vitro and in vivo. Our findings demonstrated that KRASG12C inhibition plus SOS1 degradation as a potential therapeutic strategy to improve antitumor response and overcome acquired resistance to KRASG12C inhibitor.

CXC ligand 13 orchestrates an immunoactive microenvironment and enhances immunotherapy response in head and neck squamous cell carcinoma.

Objectives: This study aims to systematically explore the role of chemokine CXC ligand 13 (CXCL13) in head and neck squamous cell carcinoma (HNSCC). Methods: The Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases provided the RNA-seq data for cancer and normal tissues, respectively. Gene set enrichment analysis was applied to search the cancer hallmarks associated with CXCL13 expression. TIMER2.0 was the main platform used to investigate the immune cell infiltration related to CXCL13. Immunohistochemistry was applied to explore the relationship between CXCL13 and patients' prognosis and the relationship between CXCL13 and tertiary lymphoid structures (TLSs). Results: The expression of CXCL13 was upregulated in most tumors, including HNSCC. The higher expression of CXCL13 was closely related to the positive prognosis of HNSCC. CXCL13 was mainly expressed in B cells and CD8 + T cells, revealing the relationship between its expression and immune activation in the tumor microenvironment. Furthermore, immunohistochemistry and multiple fluorescence staining analysis of HNSCC samples showed a powerful correlation between CXCL13 expression, TLSs formation, and positive prognosis. Finally, CXCL13 significantly increased the response to cancer immunotherapy. Conclusions: CXCL13 may function as a potential biomarker for predicting prognosis and immunotherapy response and associate with TLSs in HNSCC.

Multidisciplinary-derived clinical score for accurate prediction of long-term mortality in fibrotic lung disease patients.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) stands out as one of the most aggressive forms of interstitial lung diseases (ILDs), currently without a definitive cure. Multidisciplinary discussion (MDD) is now considered a cornerstone in diagnosing and differentiating ILD subtypes. The Gender-Age-Physiology (GAP) score, developed to assess IPF prognosis based on sex, age, forced vital capacity, and diffusion capacity for carbon monoxide (DLCO), is limited in not considering dyspnea and functional impairment during the walking test. We proposed a MDD-based clinical score for mortality prediction among those patients. METHODS: From December 2018 to December 2019, we enrolled ILD patients with IPF and non-IPF and followed-up them till December 2020. Based on DLCO, modified Medical Research Council (mMRC) Dyspnea Scale, and six-minute walking test (6MWT) distance, a functional score was developed for mortality prediction. RESULTS: We enrolled 104 ILD patients, 12 (11.5%) died by the one-year follow-up. In receiver operating characteristic (ROC) curve analysis, DLCO (% predicted) was the most accurate variable predicting one-year mortality with an area under curve (AUC) of 0.88 (95% confidence interval [CI] = 0.80-0.94), followed by mMRC Dyspnea Score (AUC = 0.82 [95% CI = 0.73-0.89]), 6MWT distance (AUC = 0.80 [95% CI = 0.71-0.88]), and GAP score (AUC = 0.77 [95% CI = 0.67-0.84]). Only the GAP score (hazard ratio [HR] = 1.55, 95% CI = 1.03-2.34, p = 0.0.37) and functional score (HR = 3.45, 95% CI = 1.11-10.73, p = 0.032) were significantly associated with one-year mortality in multivariable analysis. CONCLUSION: The clinical score composite of DLCO, mMRC Dyspnea Scale, and 6MWT distance could provide an accurate prediction for long-term mortality in ILD patients, laying out a helpful tool for managing and following these patients.

Prospective observational study of surgery alone for locally advanced oral squamous cell carcinoma: a real-world study.

INTRODUCTION: A prospective observational study was modified to assess the efficacy of surgery alone for the treatment of locally advanced oral squamous cell carcinoma. (LA-OSCC) MATERIALS AND METHODS: This prospective, single-institution, single-arm study involved 174 patients who underwent major surgery for LA-OSCC. Participating patients did not receive postoperative radiation. After initial curative treatment, patients were routinely monitored via clinical examination and imaging. The follow-up period was 3-70 months. Tumour recurrence and death were considered as the Clinical End Point in Research. RESULTS: The 5-year overall survival (OS), disease-free survival (DFS), and locoregional control rates for 174 patients were 66.7% (95% confidence interval [CI], 59.8 to 73.6), 66.1% (95% CI, 59.2 to 73.0), and 82.4% (95% CI, 76.5 to 88.3), respectively. CONCLUSION: A study of patients with LA-OSCC treated with surgery alone may have the optimal therapeutic impact for LA-OSCC, as evidenced by solid data for our next RCT trial. This conclusion still needs to be validated in higher-level RCTs.

Ultrathin 2D As2Se3 Nanosheets for Photothermal-Triggered Cancer Immunotherapy.

Arsenic trioxide (As2O3) has achieved groundbreaking success in the treatment of acute promyelocytic leukemia (APL). However, its toxic side effects seriously limit its therapeutic application in the treatment of solid tumors. To detoxify the severe side effects of arsenic, herein we synthesized innovative 2D ultrathin As2Se3 nanosheets (As2Se3 NSs) with synergistic photothermal-triggered immunotherapy effects. As2Se3 NSs are biocompatible and biodegradable under physiological conditions and can release As(III) and Se(0). Furthermore, selenium increases the immunomodulatory efficacy of arsenic treatments, facilitating reprogramming of the tumor microenvironment by As2Se3 NSs by enhancing the infiltration of natural killer cells and effector tumor-specific CD8+ T cells. The synergistic combination of photothermal therapy and immunotherapy driven by As2Se3 NSs via a simple but effective all-in-one strategy achieved efficient anticancer effects, addressing the key limitations of As2O3 for solid tumor treatment. This work demonstrates not only the great potential of selenium for detoxifying arsenic but also the application of 2D As2Se3 nanosheets for cancer therapy.

Exosomal microRNAs as biomarkers for viral replication in tofacitinib-treated rheumatoid arthritis patients with hepatitis C.

Notwithstanding recent advances in direct antiviral specialists (DAAs) for hepatitis C infection (HCV), it is yet a pervasive overall issue in patients with rheumatoid arthritis (RA). Exosomal microRNAs (miRNAs) is associated with HCV infection. However, it remains unknown how miRNAs respond following biologic disease-modifying antirheumatic drug (bDMARD) and targeted synthetic DMARD (tsDMARD) treatment in HCV patients with RA. We prospectively recruited RA patients taking anti-tumor necrosis factor-α (TNF-α) inhibitors rituximab (RTX) and tofacitinib. The serum hepatitis C viral load was measured using real-time quantitative reverse transcriptase PCR before and 6 months after bDMARD and tsDMARD therapy. HCV RNA replication activity was measured using an HCV-tricistronic replicon reporter system, and quantitative analysis of hsa-mir-122-5p and hsa-mir-155-5p in patients was performed using quantitative PCR. HCV RNA replication in hepatocytes was not affected by tofacitinib or TNF-α inhibitor treatment. Hsa-mir-155-5p and hsa-mir-122-5p were significantly expanded in RA patients with HCV as compared with those without HCV. We observed a dramatic increase in hsa-mir-122-5p and a decrease in hsa-mir-155-5p expression levels in patients taking RTX in comparison with other treatments. Finally, a reduction in hsa-mir-122-5p and an increase in hsa-mir-155-5p were observed in a time-dependent manner after tofacitinib and DAA therapy in RA-HCV patients. These results showed that hsa-mir-155-5p and hsa-mir-122-5p were significantly increased in RA-HCV patients as compared with those without HCV after taking tofacitinib. Hsa-mir-155-5p and hsa-mir-122-5p may be potential biomarkers for treatment efficacy in RA patients with HCV.

Association between HNF4A rs1800961 polymorphisms and gallstones in a Taiwanese population.

BACKGROUND AND AIM: A large genetic effect of a novel gallstone-associated genetic variant, the hepatocyte nuclear factor 4α (HNF4A) rs1800961 polymorphism, has been identified through recent genome-wide association studies. However, this effect has not been validated in Asian populations. We investigated the association between the rs1800961 variant and gallstones among a Taiwanese population. METHODS: A total of 20 405 participants aged between 30 and 70 years voluntarily enrolled in the Taiwan Biobank. Self-report questionnaires, physical examinations, biochemical tests, and genotyping were used for analysis. The association of the HNF4A rs1800961 variant and other metabolic risks with gallstone disease was analyzed using multiple logistic regression models. RESULTS: The minor T allele of HNF4A rs1800961 was associated with an increased risk of gallstone, and the association remained significant even after adjustment for other risk factors including age, body mass index (BMI), diabetes, hyperlipidemia, hypertension, and cigarette smoking (adjusted odds ratio [OR] = 1.90, 95% confidence interval [CI] = 1.31 to 2.75) in male participants. When further stratified by BMI and age, the lithogenic effect was the most significant in male participants with obesity (adjusted OR = 3.55, 95% CI = 1.92 to 6.56) and who were younger (adjusted OR = 2.45, 95% CI = 1.49 to 4.04). CONCLUSION: The novel gallstone-associated HNF4A rs1800961 variant was associated with the risk of gallstone in the Taiwanese men. Screening for the rs1800961 polymorphism may be particularly useful in assessing the risk of gallstone formation in younger or obese men.

Potential alleviation of bone mineral density loss with Janus kinase inhibitors in rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is characterized by localized bone loss, general osteoporosis and increased fracture risks. Tumour necrosis factor inhibitors (TNFi), non-tumour necrosis factor inhibitors (non-TNFi) biologic, Janus kinase inhibitors (JAKi) had shown the suppression effects to osteoclast activation and improvement of bone mineral density (BMD). Anti-cyclic citrullinated peptide antibody (ACPA) is associated with osteoclast activation and the resultant bone loss. However, few studies have compared BMD changes among patients with RA treated with targeted therapies that have different mechanisms of action. METHODS: This retrospective study recruited patients with RA who had undergone BMD testing twice. Changes in the BMD were compared using the generalized estimating equation (GEE) in treatment groups that received conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), TNFi, non-TNFi biologics, and JAKi. RESULTS: In total, 362 patients with RA were enrolled (csDMARDs, n = 153, TNFi, n = 71, non-TNFi biologics, n = 108, JAKi, n = 30). We observed greater changes in femoral BMD (left, 0.06, 95% CI 0.01-0.12, p = 0.016; right, 0.09, 95% CI 0.04-0.15, p = 0.001 by GEE) following JAKi treatment as compared with other treatments. Compared to the ACPA-negative group, patients with ACPA positivity exhibited greater improvement in the femoral BMD (left, 0.09, 95% CI 0.02-0.15, p = 0.008; right, 0.11, 95% CI 0.05-0.18, p = 0.001). CONCLUSION: Compared to other targeted therapies, JAKi might exert a more potent effect to prevent BMD loss, specifically in ACPA-positive patients with RA, and could be a potential therapeutic option to mitigate generalized bone loss. Key Points •JAKi therapy inhibits systemic bone loss in patients with RA. •ACPA-positive RA patients exhibited a greater BMD improvement than ACPA-negative RA patients. •JAKi might more potently prevent BMD decline than conventional synthetic or biological DMARDs.

Gender-specific linkages: frailty, polypharmacy, anti-cholinergic burden, and 5-year mortality risk-a real-world analysis.

Background: With higher age, frailty escalates the risk of falls, unexpected physical dysfunction, hospitalization, and mortality. Polypharmacy in the older population is a major challenge that not only increases medical costs, but also may worsen the risk of hospitalization and death. More importantly, the properties of anti-cholinergic drugs contribute various negative effects. This study aimed to investigate the sex difference in the association of polypharmacy, anticholinergic burden, and frailty with mortality. Methods: Participants older than 65 years who attended the geriatric outpatient clinic of the study center between January 2015 and July 2020 were invited to participate in this retrospective study. Comprehensive geriatric assessment data were collected and the phenotype of frailty was determined by Fried's criteria. Cox regression and the Kaplan-Meier curve were used to identify risk factors of 5-year survival along with intergroup differences in the risks. Results: Of the 2,077 participants, 47.5% were female. The prevalence of frailty and the rate of polypharmacy were 44.7% and 60.6%, respectively. Higher age, male sex, low body mass index, low Mini-Mental State Examination scores, low activities of daily living, frailty status, polypharmacy, and a high Charlson Comorbidity Index score, and greater anticholinergic burden were significant risk factors that were associated with the 5-year all-cause mortality. Male patients with frailty exhibited the highest risks of mortality compared with male patients without frailty and female patients with or without frailty. Polypharmacy was significantly associated with a higher 5-year mortality rate in the frail male group compared with the non-frail male. In frail female group, individuals with a higher anticholinergic burden (as indicated by the Anticholinergic Cognitive Burden Scale) from drug usage exhibited an elevated 5-year mortality rate. Conclusions: Polypharmacy and greater anticholinergic burden, synergistically interacted with frailty and intensified the 5-year mortality risk in a gender-specific manner. To mitigate mortality risks, clinicians should prudently identify polypharmacy and anticholinergic burden in the older population.

Case Report: Multiple gastrointestinal stromal tumors along with numerous cutaneous neurofibromas: a case description and literature analysis.

Multiple gastrointestinal stromal tumors (GISTs) combined with cutaneous multiple neurofibromas are clinically rare. This paper presents a case of multiple gastrointestinal stromal tumors in the jejunum of a 68-year-old mother, along with her daughter who also had coexisting cutaneous multiple neurofibromas. The mother had been experiencing repeated melena for over 2 years and had previously been diagnosed with multiple small intestinal masses at other hospitals. Additionally, her 42-year-old daughter was admitted to our department due to recurrent abdominal pain caused by cholecystolithiasis. The mother and daughter both exhibited multiple nodular masses of varying sizes on their skin, including the truncus, limbs, and face, which were diagnosed as neurofibromas. The mother underwent a partial excision of the jejunum and a lateral jejunojejunal anastomosis side-to-side, as well as excision of skin lesions in our department. The final diagnosis of wild-type GISTs associated with neurofibromatosis type 1 (NF1) was confirmed through postoperative pathology, immunohistochemistry, and genetic testing results. During preoperative gastrointestinal endoscopy and intraoperative laparoscopic exploration of the gastrointestinal tract, no obvious tumors were found in her daughter. A combination of patient observations and a review of relevant literature in the field suggests that when patients present with gastrointestinal symptoms and multiple irregular painless swellings in the skin, it is important to consider the possibility of an association with NF1 and GIST. Additionally, obtaining a detailed family history can save time and improve the diagnosis of patients with both NF1 and GIST. We recommend that even if there are no gastrointestinal manifestations of GISTs in the offspring of newly mutated NF1 patients, regular review of gastroenteroscopy, imaging examination, and long-term follow-up after middle age are still crucial for the early diagnosis and treatment of NF1-related GISTs.

Multi-view progression diagnosis of thyroid cancer by integrating platelet transcriptomes and blood routine tests.

Thyroid cancer is the most common type of endocrine system cancer. The pre-cancer and early stages are usually benign or slowly growing, and do not need invasive treatments. This study investigated the challenging classification task of four classes of samples, i.e., normal controls (N), thyroid adenomas (TA), papillary thyroid cancers (PTC) and metastasized papillary thyroid cancers (MPTC). We proposed a multi-view progression diagnosis framework ThyroidBloodTest to integrate the two views of RNAseq platelet transcriptomes (View-T) and blood routine (View-B) features. Platelet transcriptome represented the molecular-level information, while the blood routine features were easy to obtain in the clinical practice. Eleven feature selection algorithms and seven classifiers were evaluated for both views. The experimental data suggested the importance of choosing appropriate data analysis algorithms and feature engineering techniques like principal component analysis (PCA). The best ThyroidBloodTest model achieved Acc = 0.8750 for the four-class classification of the N/TA/PTC/MPTC samples based on the integrated feature space of View-T and View-B. The cellular localization cytosol and three post-translational modification types acetylation/phosphorylation/ubiquitination were observed to be enriched in the proteins encoded by the View-T biomarkers. The numbers of different immune cells also contributed positively to the progression diagnosis of thyroid cancer. The proposed multi-view prediction model demonstrated the necessity of integrating both platelet transcriptomes and blood routine tests for the progression diagnosis of thyroid cancer.

Risk Prediction of Chronic Rhinosinusitis with or without Nasal Polyps in Taiwanese Population Using Polygenic Risk Score for Nasal Polyps.

The association between single nucleotide polymorphisms and chronic rhinosinusitis (CRS) has been determined. However, it was not known whether the polygenic risk score (PRS) for nasal polyps (NP) could predict CRS with NP (CRSwNP) or without NP (CRSsNP). The aim of this study was to investigate the association between PRSs for NP and the risk of CRS with or without NP. Data from 535 individuals with CRS and 5350 control subjects in the Taiwan Precision Medicine Initiative project were collected. Four PRSs for NP, including PGS000933, PGS000934, PGS001848, and PGS002060 from UK Biobank, were tested in these participants. They were divided into four groups according to quartiles of PRSs. The logistic regression model was performed to evaluate CRSwNP and CRSsNP risk according to PRSs for NP. The PGS002060 had the highest area under the curve at 0.534 for CRSsNP prediction and at 0.588 for CRSwNP prediction. Compared to subjects in the lowest PRS category, the PGS002060 significantly increased the odds for CRSsNP by 1.48 at the highest quintile (p = 0.003) and by 2.32 at the highest quintile for CRSwNP (p = 0.002). In addition, the odds for CRSwNP increased by 3.01 times in female CRSwNP patients (p = 0.009) at the highest quintile compared with those in the lowest PRS category. The PRSs for NP developed from European populations could be applied to the Taiwanese population to predict CRS risk, especially for female CRSwNP.

High expression ITGA2 affects the expression of MET, PD-L1, CD4 and CD8 with the immune microenvironment in pancreatic cancer patients.

Purpose: Pancreatic cancer is characterized by a grim prognosis and is regarded as one of the most formidable malignancies. Among the genes exhibiting high expression in different tumor tissues, ITGA2 stands out as a promising candidate for cancer therapy. The promotion of cancer in pancreatic cancer is not effective. The objective of this study is to assess the presence of ITGA2, EMT and PD-L1 in pancreatic cancer. Experimental design: We examined the expression of ITGA2, MET, E-cadherin, PD-L1, CD4, and CD8 proteins in 62 pancreatic cancer tissue samples using multi-tissue immunofluorescence and immunohistochemistry techniques. Functional assays, such as the cell migration assay and transwell assay, were used to determine the biological role of ITGA2 in pancreatic cancer. The relationship of ITGA2,EMT and PD-L1 were examined using Western blot analysis and RT-qPCR assay. Results: In our study, we observed the expression of ITGA2, E-cadherin, and PD-L1 in both tumor and stroma tissues of pancreatic cancer. Additionally, a positive correlation between ITGA2, E-cadherin, and PD-L1 in the tumor region (r=0.559, P<0.001 and r=0.511, P<0.001), and PD-L1 in the stroma region (r=0.512, P<0.001).The expression levels of ITGA2, CD4, and CD8 were found to be higher in pancreatic cancer tissues compared to adjacent tissues (P < 0.05). Additionally, ITGA2 was negatively correlated with CD4 and CD8 (r = -0.344, P < 0.005 and r = -0.398, P < 0.005).Furthermore, ITGA2, CD4, and CD8 were found to be correlated with the survival time of patients (P < 0.05). Blocking ITGA2 inhibited the proliferation and invasion ability of pancreatic cancer cells significantly, Additionally, sh-ITGA2 can down-regulate the expression of EMT and PD-L1. Conclusions: We identified a novel mechanism in which ITGA2 plays a crucial role in the regulation of pancreatic cancer growth and invasion. This mechanism involves the upregulation of MET and PD-L1 expression in pancreatic cancer cells. Additionally, we found that increased expression of ITGA2 is associated with a poor prognosis in pancreatic cancer patients. Furthermore, ITGA2 also affects immune regulation in these patients. Therefore, targeting ITGA2 is an effective method to enhance the efficacy of checkpoint immunotherapy and prohibiting tumor growth against pancreatic cancer.

The fibrinogen-albumin ratio as a novel prognostic factor for elderly patients with osteosarcoma.

To analyze the prognostic value of fibrinogen-albumin ratio (FAR) in predicting the overall survival in elderly osteosarcoma patients. One hundred nineteen elderly osteosarcoma patients (> 40 years old) from 2 centers were retrospectively reviewed and analyzed. The cutoff values of the biomarker were calculated via receiver operating characteristic curves, and the cohort was divided into high FAR group and low FAR group. The association between the FAR and clinical-pathological parameters was analyzed. And the prognosis of elderly osteosarcoma patients and the potential risk factors were analyzed using Kaplan-Meier method and Cox proportional hazards model. Finally, a clinical nomogram was constructed, and its predictive capacity was verified. According to receiver operating characteristic results, the cutoff value for FAR was 0.098, and the enrolled patients were divided into the low FAR group and high FAR group. The FAR was significantly correlated with several clinical-pathological characteristics, including age, tumor size, tumor stage, recurrence, and metastasis. Moreover, the multivariate Cox analyses results showed that the FAR, pathological fracture, and metastasis were independent risk factors for overall survival in elderly osteosarcoma patients. The predictive nomogram was subsequently constructed, representing satisfactory predictive performance for prognosis in elderly patients with osteosarcoma. The FAR value is a promising indicator for elderly osteosarcoma patients, which is correlated with the various clinical characteristics and prognosis. A clinical nomogram integrating FAR and other clinical indicators is a convenient and available tool to assess the prognosis and manage the individualized and precise treatment of elderly patients with osteosarcoma.

Efficacy of quaternary ammonium salt-based disinfectant or chelated copper-zinc footbath solution in the treatment of digital dermatitis on one research dairy farm in Taiwan.

BACKGROUND: Footbaths can be used to manage digital dermatitis (DD), a common cause of lameness in dairy cattle. Copper sulfate and chelated copper-zinc (CZS) solutions in footbaths are potentially harmful to the environment. HYPOTHESIS/OBJECTIVES: To determine if a quaternary ammonium salt-based disinfectant (QASD) footbath is as effective as a chelated CZS solution in controlling DD in dairy cows. ANIMALS: Fifty-one lactating Holstein cows were randomly assigned to one of two treatment groups, with DD status based on the M-stage scoring system and locomotion score balanced between treatment groups. MATERIALS AND METHODS: The groups were treated with a 1% QASD or a 2.5% chelated CZS. Footbaths were performed once per week for 15 weeks. Logistic regression was used to analyse clinical improvement. All cows received appropriate medical treatment for DD and other hoof diseases. RESULTS: Clinical improvement rates were 67% in the QASD group and 38% in the CZS group (p = 0.03). Logistic regression analysis showed that the odds (95% confidence interval) for clinical improvement rate in the CZS group were 0.30 (0.095-0.948) times that of the QASD group (p = 0.04). The M0 score in the QASD and CZS groups increased significantly (p < 0.05) at the end of the 15 week study period. In the QASD group, the proportion of M2, M3 and M4 scores were significantly decreased (p < 0.05). CONCLUSION AND CLINICAL RELEVANCE: Over a 15 week period, QASD for footbathing was associated with a lower prevalence of active DD lesions than when using CZS.