anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Solifenacin was evaluated in four twelve-week, double-blind, randomized, placebo-controlled, parallel group, multicenter clinical trials for the treatment of overactive bladder in patients having symptoms of urinary frequency, urgency, and/or urge or mixed incontinence (with a predominance of urge). Entry criteria required that patients have symptoms of overactive bladder for ≥ 3 months duration. These studies involved 3027 patients (1811 on Solifenacin and 1216 on placebo), and approximately 90% of these patients completed the 12-week studies. Two of the four studies evaluated the 5 and 10 mg Solifenacin doses and the other two evaluated only the 10 mg dose. All patients completing the 12-week studies were eligible to enter an open label, long term extension study and 81% of patients enrolling completed the additional 40-week treatment period. The majority of patients were Caucasian (93%) and female (80%) with a mean age of 58 years.

The primary endpoint in all four trials was the mean change from baseline to 12 weeks in number of micturitions/24 hours. Secondary endpoints included mean change from baseline to 12 weeks in number of incontinence episodes/24 hours, and mean volume voided per micturition. The efficacy of Solifenacin was similar across patient age and gender. The mean reduction in the number of micturitions per 24 hours was significantly greater with Solifenacin 5 mg (2.3; p<0.001) and Solifenacin 10 mg (2.7; p<0.001) compared to placebo, (1.4).

The mean reduction in the number of incontinence episodes per 24 hours was significantly greater with Solifenacin 5 mg (1.5; p<0.001) and Solifenacin 10 mg (1.8; p<0.001) treatment groups compared to placebo (1.1). The mean increase in the volume voided per micturition was significantly greater with Solifenacin 5 mg (32.3 mL; p<0.001) and Solifenacin 10 mg (42.5 mL; p<0.001) compared with placebo (8.5 mL).

The results for the primary and secondary endpoints in the four individual 12-week clinical studies of Solifenacin are reported in Tables 3 through 6.
INTRODUCTION: Skewed immune response plays a pivotal role in tumor progression. Systemic inflammatory responses represented by combined peripheral leukocyte fractions are prognostic predictors of multiple cancers, including thyroid cancer. We previously reported the prognostic significance of lymphocyte-to-monocyte ratio (LMR) in curatively resected papillary thyroid cancer (PTC). Therefore, this study aimed to analyze immune cell profiles in the tumor microenvironment and their association with LMR in curatively resected PTC.
MATERIALS AND METHODS: The immune cell profiles of primary tumors in 162 patients with curatively resected PTC were analyzed clinicopathologically. Immunohistochemistry of tumor-associated macrophages (TAMs), myeloid-derived suppressor cells, and lymphocytes was performed using CD163, CD33, and CD3 antibodies, respectively. Prognostic analysis and correlation assays were performed using the immunocyte profiles. The gene expression of tumor-derived chemokines was assessed using a The Cancer Genome Atlas database.
RESULTS: Patients with a higher density of CD163+ TAMs exhibited a significantly worse prognosis than their counterparts (10-y recurrence-free survival: 80.9% versus 91.2%, P = 0.011). Multivariate prognostic analyses revealed that high CD163+ cell density (P = 0.011), low preoperative LMR (P = 0.003), pN1b (P = 0.005), and high thyroglobulin level (P = 0.038) were independent predictors of recurrence. High CD163+ cell density had a prognostic impact on stage II and III PTC. Interestingly, high CD163+ cell density correlated with low LMR and high monocyte fraction in peripheral blood. Indeed, the expression of TAM-inducible, tumor-derived chemokines is increased in the The Cancer Genome Atlas database.
CONCLUSIONS: A high density of infiltrated CD163+ TAMs predicts recurrence in correlation with low LMR and circulating monocyte accumulation. Thus, TAMs should be considered when assessing advanced PTC.
In spite of the improved medical treatment, rheumatoid arthritis (RA) is still causing both significant morbidity and marked loss of work productivity. Short periods of work inability, i.e., sick leaves represent a significant part of the socioeconomic burden of RA. The study is a randomized, controlled double blind multi-center study. 160 patients of 25 to 55 years of age with recent-onset (≤2 years from diagnosis) RA who have been treated with a combination of conventional antirheumatic drugs but have an inadequate response to treatment and are at the risk of losing their ability to work, are enrolled. The patients should be biologic-naïve. Their RA should be active, but not so active that the conventional criteria for biologic therapy would be fulfilled. The subjects are randomized at 1:1 ratio to receive either adalimumab (40 mg every two weeks) or placebo for 6 months added on their concurrent antirheumatic therapy. The RA-related sickness absence and clinical response will be evaluated.
Bilateral hysteroscopic placement of the permanent birth control system, Model ESS505 insert with minimal polyethylene terephthalate (PET) fibers (investigational device model ESS505-A) followed by tubal occlusion evaluation by hysterosalpingogram (HSG) approximately 60 minutes following insert placement. A subsequent HSG was performed prior to the subjects' scheduled hysterectomy procedures at 30 (group 3), 60 (group 2) or 90 days (group 1) post insert placement.
Patient will take (R)-9bMS twice daily by mouth for up to 6 months. Each cycle is 28 days. The assigned dose will be determined in the Dose Escalation portion of the trial.
1,212,704. Vaginal suppositories. SPASOC. PRODOTTI ANTIBIOTICI S.p.A. 21 Nov., 1968 [21 Nov., 1967], No. 52945/67. Heading A5B. A varginal suppository comprises at least one surfaceactive fatty compound as defined, an effervescent compound or couple, at least one pharmaceutically active compound and optionally at least one other pharmaceutical excipient. The pharmaceutically active ingredients are chosen from lysozyme or a non- toxic salt thereof, a nitroimidazole compound, an antibiotic such as a tetracycline compound or chloramphenicol, a penicillin or a steroid such as oestrogen.
Patients received 6 cycles of induction chemotherapy: Cyclophosphamide, Doxorubicin, Vincristine, Etoposide and Prednisone (CHOEP) (5 if previously received 1 cycle of CHOP). CHOP was given at standard doses, with a dose of etoposide of 100 mg/m2 intravenously (IV) or 200 mg/m2 orally added on days 1-3 of each cycle. Patients who did not achieve a partial (PR) or complete (CR) remission at restaging after either 3 or 6 cycles were taken off study. Responders after 6 cycles had stem cell (SC) mobilization using filgrastim and plerixafor (if necessary) within 4 weeks of the end of induction. SC mobilization, harvesting, and reinfusion were performed per standard institutional protocol. A minimum collection of 2x106 CD34+ cells/kg was required to proceed to autologous stem cell transplant. Conditioning was comprised of gemcitabine 2700 mg/m2 on days -8 and -3, IV busulfan 105 mg/m2 days -8 to -5, and melphalan 60 mg/m2 given daily on days -3 and -2 (per MD Andersen protocol).
Morphine has been suggested to affect cancer cell dynamics and decrease survival rates in lung cancer patients at specific doses, but the precise mechanisms poorly understood. In this study, we aimed to investigate the molecular mechanisms by which morphine modulates the malignant characteristics of non-small cell lung cancer. Cell proliferation was assessed via the Cell Counting Kit-8 assay, and cell migration and invasion were examined via wound healing and Transwell assays. We employed immunofluorescence staining to evaluate E-cadherin expression in A549 and Lewis lung cancer (LLC) cell lines and immunohistochemistry to evaluate E-cadherin expression in nude mice tumours. Additionally, the in vivo effects of morphine on lung cancer progression were explored in a xenograft tumour experiments, in which naloxone was used as a morphine antagonist. Western blot analysis was performed to detect E-cadherin, phosphorylated mTOR (p-mTOR), mTOR, phosphorylated AKT (p-AKT), AKT, phosphorylated PI3K (p-PI3K), and PI3K protein levels in A549 and LLC cells as well as in tumour samples. Morphine (10 µM) significantly increased the proliferation of A549 and LLC cells in vitro (p < 0.05). It also enhanced the migratory and invasive capacities of these cell lines (p < 0.01). Mechanistically, morphine treatment (10 µM) led to a reduction in the expression of E-cadherin, and an increase in the phosphorylation of PI3K, AKT, and mTOR in A549 and LLC cells (p < 0.01). Morphine treatment (1.5 mg/kg) also reduced E-cadherin expression in xenograft tumours and promoted tumour growth in vivo (p < 0.05). This effect was reversed by naloxone (0.1 mg/kg). The results demonstrated that morphine stimulates the malignant proliferation of A549 and LLC cell lines and promotes xenograft tumour growth. Perhaps by specifically targeting MOR, morphine triggers a signalling cascade that activates the PI3K/AKT/mTOR pathway while inhibiting the EMT marker E-cadherin, which may consequently promote the progression of lung cancer.
Age at diagnosis (AAD) of Type 1 diabetes (T1D) is determined by the age at onset of the autoimmune attack and by the rate of beta cell destruction that follows. Twin studies found that T1D AAD is strongly influenced by genetics, notably in young children. In young UK, Finnish, Sardinian patients AAD-associated genomic variants were previously identified, which may vary across populations and with time. In 1956 children of European ancestry born in mainland France in 1980-2008 who declared T1D before 15 years, we tested 94 T1D-associated SNPs for their association with AAD using nonparametric Kruskal-Wallis test. While high-risk HLA genotypes were not found to be associated with AAD, fourteen SNPs located in 12 non-HLA loci showed a strong association (2.9 × 10-12 < P < 1.4 × 10-3 after FDR correction). Four of these loci have been associated with AAD in previous cohorts (GSDMB, IL2, TNFAIP3, IL1), supporting a partially shared genetic influence on AAD of T1D in the studied European populations. In contrast, the association of 8 new loci CLEC16A, TYK2, ERBB3, CCR7, FCRL3, DNAH2, FGF3/4, and HPSE2 with AAD is novel. The 12 protein-coding genes located within these loci are involved in major immune pathways or in predisposition to other autoimmune diseases, which suggests a prominent role for these genes in the early immune mechanisms of beta cell destruction.
Bilateral NIRS (The INVOS® Cerebral/Somatic Oximeter)will be used to measure rSO2 intraoperatively and during the 24h postoperative period in the intensive care unit. In the intervention group, an alarm threshold at 75% of the baseline rSO2 value will be established.
PURPOSE: To investigate the relationship between preoperative systemic immune-inflammation index (SII) and relapse-free survival (RFS) after surgical resection of mucoepidermoid carcinoma(MEC).
METHODS: The data of 135 patients with MEC who underwent surgical resection in the First Affiliated Hospital of Zhengzhou University from January 2016 to July 2019 were collected, and the receiver operating characteristic(ROC) curve was performed on the SII of patients. The optimal cut-off value was obtained by ROC analysis. Therefore, the patients' SII index was divided into high and low group, and survival analysis was performed by Kaplan-Meier method. Cox proportional regression model and least absolute shrinkage and selection operator (LASSO) were used to analyze the factors influencing prognosis, and a nomogram model was built to predict patients' relapse-free survival(RFS). Area under curve (AUC) and correction curve were used to evaluate the model and verify the consistency.
RESULTS: Survival analysis showed that the RFS rate in low SII group was significantly higher than that in high SII group. Cox proportional hazard regression model showed high SII(HR=2.179, 95%CI: 1.072-4.426, P=0.031) and low tumor differentiation(HR=6.894, 95%CI: 2.770-17.158, P=0.000) and cervical lymph node metastasis (HR=2.091, 95%CI: 1.034-4.230, P=0.040) were significant predictors of poor RFS.
CONCLUSIONS: The lower the preoperative SII, the better the prognosis of patients. The nomogram prognosis of MEC based on SII is effective.
The long-term effects of SARS-CoV-2 infection represent a relevant global health problem. Long COVID (LC) is defined as a complex of signs and symptoms developed during or after SARS-CoV-2 infection and lasting > 12 weeks. In common variable immunodeficiency (CVID) patients, we previously reported higher risk of hospitalization and death during SARS-CoV-2 infection, as well as prolonged swab positivity and frequent reinfections. The aim of the present study was to assess the risk of LC in an Italian cohort of CVID patients. We used a translated version of the survey proposed by Centers for Disease Control and Prevention (CDC) to collect data on LC. In the enrolled cohort of 175 CVID patients, we found a high prevalence of LC (65.7%). The most frequent LC symptoms were fatigue (75.7%), arthralgia/myalgia (48.7%), and dyspnea (41.7%). The majority of patients (60%) experienced prolonged symptoms, for at least 6 months after infection. In a multivariate analysis, the presence of complicated phenotype (OR 2.44, 95% CI 1.88-5.03; p = 0.015), obesity (OR 11.17, 95% CI 1.37-90.95; p = 0.024), and female sex (OR 2.06, 95% CI 1.09-3.89; p = 0.024) significantly correlated with the development of LC. In conclusion, in this multicenter observational cohort study, we demonstrated that CVID patients present an increased prevalence of LC when compared to the general population. Improved awareness on the risk of LC in CVID patients could optimize management of this new and alarming complication of SARS-CoV-2 infection.
The invention provides a small RNA and a small RNA composition of a PIANZAIHUANG for preventing and/or treating alcoholic liver injury, and a preparation method and application thereof, and belongs to the technical field of biological medicines. The small RNA of the invention is a nucleotide sequence shown in any one of SEQ ID NO. 1-3, SEQ ID NO.6, SEQ ID NO. 8-16, SEQ ID NO. 18-31 and SEQ ID NO.33, and the small RNA composition is composed of the nucleotide sequences shown in SEQ ID NO. 1-33 as components. The 33 kinds of small RNAs extracted from the Tze Huang can be effectively absorbed by ingestion and stably exist, so that the efficacy of preventing and/or treating alcoholic liver injury is exerted; and, the composition obtained by combining these 33 kinds of small RNAs has a preventive and therapeutic effect on alcoholic liver injury. The 33 small RNAs can also be used as markers for quality control of the Pianzaihuang. The research of the invention discovers that the small RNA in the PIANZAIHUANG is beneficial to preventing and treating alcoholic liver injury, which has important significance for further research and development and quality control of the PIANZAIHUANG.
BACKGROUND: Temporomandibular joint disorders (TMD) are highly prevalent among people. Numerous investigations have revealed the impact of gut microbiota in many diseases. However, the causal relationship between Temporomandibular joint disorders and gut microbiota remains unclear.
METHODS: Genome-Wide Association Studies (GWAS) refer to the identification of sequence variations, namely single nucleotide polymorphisms (SNPs), existing across the entire human genome. GWAS data were collected on gut microbiota and TMD. Then, instrumental variables were screened through F-values and removal of linkage disequilibrium. These SNPs underwent mendelian analysis using five mathematical models. Sensitivity analysis was conducted to further verify the stability of the results. Pathogenic factors of TMD mediate the causal relationship between gut microbiota and TMD were explored through a two-step Mendelian randomization analysis. Finally, reverse mendelian analysis was conducted to account for potential reverse effects.
RESULTS: The analysis of the data in this article suggests that some gut microbiota, including Coprobacter, Ruminococcus torques group, Catenibacterium, Lachnospiraceae, Turicibacter, Victivallis, MollicutesRF9, Methanobacteriales, Methanobacteriaceae, FamilyXI, Methanobacteria were identified as risk factors, while Peptococcaceae provides protection for TMD.
CONCLUSION: The research reveals the relation of gut microbiota in TMD. These findings provide insights into the underlying mechanisms and suggest potential therapeutic strategy.
Olfactory dysfunction is one of the most common symptoms of COVID-19. In the first 2 years of the pandemic, it was frequently reported, although its incidence has significantly decreased with the emergence of the Omicron variant, which has since become the dominant viral strain. Nevertheless, many patients continue to suffer from persistent dysosmia and dysgeusia, making COVID-19-associated olfactory dysfunction an ongoing health concern. The proposed pathogenic mechanisms of COVID-19-associated olfactory dysfunction are complex and likely multifactorial. While evidence suggests that infection of sustentacular cells and associated mucosal inflammation may be the culprit of acute, transient smell loss, alterations in other components of the olfactory system (e.g., olfactory receptor neuron dysfunction, olfactory bulb injury and alterations in the olfactory cortex) may lead to persistent, long-term olfactory dysfunction. This review aims to provide a comprehensive summary of the epidemiology, clinical manifestations and current understanding of the pathogenic mechanisms of COVID-19-associated olfactory dysfunction.
This will be a single centre, randomized, double-blind (with respect to ketoconazole), two-way cross-over study in healthy male and female subjects. Subjects will attend for a screening visit within 28 days prior to the first treatment period. There will be two study periods, each consisting of 14 days. Ketoconazole or matching placebo will be administered for 11 days with fluticasone furoate/GW642444M inhalation powder co-administered on Days 5-11. During each period subjects will be required to report to the unit on Day -1 and will remain there until 1 hour post-dosing with ketoconazole or placebo on Day 1. Subjects will return to the unit on the mornings of Day 2 to Day 4 for dosing with ketoconazole or placebo. Subjects will then return on the evening of Day 4 and leave the unit on the morning of Day 6 (2 nights). Subjects will return to the unit on the mornings of Day 7 to Day 10 for dosing and pre-fluticasone furoate/GW642444M dose safety assessments. Subjects will return on the evening of Day 10 and leave the unit on the morning of Day 12 (2 nights). Subjects will make two outpatient visits, one in the evening on Day 12 and one in the morning on Day 13, to complete a few study related procedures. The two treatment periods will be separated by a washout of at least 7 days and no more than 14 days. Pharmacodynamic profiles for potassium, heart rate, QTc, blood pressure and serum cortisol will be taken on Day 11 with fluticasone furoate and GW642444 pharmacokinetic profiles on Days 5 and 11. Safety assessments will include vital signs, ECGs, adverse event monitoring and laboratory safety tests, plus blood glucose and blood potassium profiles on Day 5.
Polystyrene microplastics (PS-MPs) are new types of environmental pollutant that have garnered significant attention in recent years since they were found to cause damage to the human respiratory system when they are inhaled. The pulmonary fibrosis is one of the serious consequences of PS-MPs inhalation. However, the impact and underlying mechanisms of PS-MPs on pulmonary fibrosis are not clear. In this study, we studied the potential lung toxicity and PS-MPs-developed pulmonary fibrosis by long-term intranasal inhalation of PS-MPs. The results showed that after exposing to the PS-MPs, the lungs of model mouse had different levels of damage and fibrosis. Meanwhile, exposing to the PS-MPs resulted in a markedly decrease in glutathione (GSH), an increase in malondialdehyde (MDA), and iron overload in the lung tissue of mice and alveolar epithelial cells (AECs). These findings suggested the occurrence of PS-MP-induced ferroptosis. Inhibitor of ferroptosis (Fer-1) had alleviated the PS-MPs-induced ferroptosis. Mechanically, PS-MPs triggered cell ferroptosis and promoted the development of pulmonary fibrosis via activating the cGAS/STING signaling pathway. Inhibition of cGAS/STING with G150/H151 attenuated pulmonary fibrosis after PS-MPs exposure. Together, these data provided novel mechanistic insights of PS-MPs-induced pulmonary fibrosis and a potential therapeutic paradigm.
Rationale: Suboptimal adherence to inhaled medications in patients with chronic obstructive pulmonary disease (COPD) remains a challenge. Objectives: To examine the sociodemographic and clinical characteristics and medication beliefs associated with adherence measured by self-report and pharmacy data. Methods: A cross-sectional analysis of data from a prospective observational cohort study of patients with COPD was completed. Participants underwent spirometry and completed questionnaires regarding sociodemographic data, inhaler use, dyspnea, social support, psychological and medical comorbidities, and medication beliefs (Beliefs about Medicines Questionnaire [BMQ]). Self-reported adherence to inhaled medications was measured with the Adherence to Refills and Medications Scale (ARMS), and pharmacy-based adherence was calculated from administrative data using the ReComp score. Multivariable linear regression was used to examine the sociodemographic, clinical, and medication-belief factors associated with both adherence measures. Results: Among 269 participants with ARMS and ReComp data, adherence was the same for each measure (38.3%), but only 18% of participants were adherent by both measures. In multivariable adjusted analysis, a 10-year increase in age (β = 0.54; 95% confidence interval, 0.14-0.94) and the number of maintenance inhalers used (β = 0.53; 0.04-1.02) were associated with increased adherence by self-report. Improved ReComp adherence was associated with chronic prednisone use (β = 0.18; 0.04-0.31) and the number of maintenance inhalers used (β = 0.11; 0.05-0.17). In adjusted analyses examining patient beliefs about medications, increases in the COPD-specific BMQ concerns score (β = -0.10; -0.17 to -0.02) were associated with reduced self-reported adherence. No significant associations between ReComp adherence and BMQ score were found in adjusted analyses. Conclusions: Adherence to inhaled COPD medications was poor as measured by self-report or pharmacy refill data. There were notable differences in factors associated with adherence based on the method of adherence measurement. Older age, chronic prednisone use, the number of prescribed maintenance inhalers used, and patient beliefs about medication safety were associated with adherence. Overall, fewer variables were associated with adherence as measured based on pharmacy refills. Pharmacy refill-based and self-reported adherence may measure distinct aspects of adherence and may be affected by different factors. These results also underscore the importance of addressing patient beliefs when developing interventions to improve medication adherence.