anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
INTRODUCTION: Despite aggressive standard-of-care therapy, including surgery, radiation, and chemotherapy, glioblastoma recurrence is almost inevitable and uniformly lethal. Activation of glioma-intrinsic Wnt/β-catenin signaling is associated with a poor prognosis and the proliferation of glioma stem-like cells, leading to malignant transformation and tumor progression. Impressive results in a subset of cancers have been obtained using immunotherapies including anti-CTLA4, anti-PD-1, and anti-PD-L1 or chimeric antigen receptor (CAR) T cell therapies. However, the heterogeneity of tumors, low mutational burden, single antigen targeting, and associated antigen escape contribute to non-responsiveness and potential tumor recurrence despite these therapeutic efforts. In the current study, we determined the effects of the small molecule, highly specific Wnt/CBP (CREB Binding Protein)/β-catenin antagonist ICG-001, on glioma tumor cells and the tumor microenvironment (TME)-including its effect on immune cell infiltration, blood vessel decompression, and metabolic changes.
METHODS: Using multiple glioma patient-derived xenografts cell lines and murine tumors (GL261, K-Luc), we demonstrated in vitro cytostatic effects and a switch from proliferation to differentiation after treatment with ICG-001.
RESULTS: In these glioma cell lines, we further demonstrated that ICG-001 downregulated the CBP/β-catenin target gene Survivin/BIRC5-a hallmark of Wnt/CBP/β-catenin inhibition. We found that in a syngeneic mouse model of glioma (K-luc), ICG-001 treatment enhanced tumor infiltration by CD3+ and CD8+ cells with increased expression of the vascular endothelial marker CD31 (PECAM-1). We also observed differential gene expression and induced immune cell infiltration in tumors pretreated with ICG-001 and then treated with CAR T cells as compared with single treatment groups or when ICG-001 treatment was administered after CAR T cell therapy.
DISCUSSION: We conclude that specific Wnt/CBP/β-catenin antagonism results in pleotropic changes in the glioma TME, including glioma stem cell differentiation, modulation of the stroma, and immune cell activation and recruitment, thereby suggesting a possible role for enhancing immunotherapy in glioma patients.
Patients participate in a standard of care treatment planning meeting over 3 hours with members of the multidisciplinary treatment team including, the oncologist, radiologist, oncology surgeon, and social worker. Patients then complete surveys over 20 minutes and within 30 days later. Some patients may participate in interviews over 30 minutes.
Neutralizing antibodies (NAbs) are considered the primary mechanism of vaccine-mediated protection against human papillomaviruses (HPV), the causative agent of cervical cancer. However, the minimum level of NAb needed for protection is currently unknown. The HPV pseudovirion-based neutralization assay (PBNA) is the gold standard method for assessing HPV antibody responses but is time-consuming and labor-intensive. With the development of higher valency HPV vaccines, alternative serological assays with the capacity for multiplexing would improve efficiency and output. Here we describe a multiplex bead-based immunoassay to characterize the antibody responses to the seven oncogenic HPV types (HPV16/18/31/33/45/52/58) contained in the current licensed nonavalent HPV vaccine. This assay can measure antibody isotypes and subclasses (total IgG, IgM, IgA1-2, IgG1-4), and can be adapted to measure other antibody features (e.g., Fc receptors) that contribute to vaccine immunity. When tested with serum samples from unvaccinated and vaccinated individuals, we found high concordance between HPV-specific IgG using this multiplex assay and NAbs measured with PBNA. Overall, this assay is high-throughput, sample-sparing, and time-saving, providing an alternative to existing assays for the measurement and characterization of HPV antibody responses.
BACKGROUND: Tinnitus is burdensome to many patients. Sound amplification and masking therapy has been useful for some patients.
METHOD: Retrospective chart review of patients treated for tinnitus at a single academic medical center over a 12-month period. Information on treatment course and outcomes was collected and analyzed. Statistical comparisons were made using a t-test for paired means.
RESULTS: In 2021, 141 patients were evaluated for tinnitus sound amplification and masking therapy at our medical center. Average age at presentation was 55.2. Average onset was 6-7 years before presentation. Tinnitus perception was decreased in patients who received a trial of amplification and masking therapy, from 9.2 out of 20 at baseline to 6.1 with amplification and 3.2 with amplification and masking at the initial visit. The difference in each of these values is statistically significant. Nine patients recorded a Tinnitus Handicap Index (THI), which measures tinnitus burden, before and after being treated with amplification and masking therapy. These nine patients saw a decrease in THI from 39.6/100 to 19.1/100, which was also statistically significant.
LIMITATIONS: This study has several limitations. Our data are from a single clinic over one year with limited follow up information, and it is a retrospective study.
CONCLUSION: Our data showed benefit in sound amplification and masking therapy for the treatment of tinnitus. Patients treated with amplification and masking therapy showed a statistically significant decrease in perception of their tinnitus during their in-office demonstration. Long term data are still needed. Our data contribute to the broader discussion on the proper treatment course of tinnitus and the most effective measures.
Revefenacin will be delivered once daily via nebulizer. In order to allow for full blinding and steady Q6 hours regimen in control arm, at hours 6, 12 and 18 after the Revefenacin dose, nebulized normal saline will be delivered.
INCA033989 will be administered as an add-on therapy in combination with ruxolitinibat at the RDE(s) identified during Part 1a. Participants with treatment Group B (TGB) MF SubOpt R will enroll in this group.
Patients receive denosumab SC on day 1 (days 1, 8, and 15 of course 1 only). Treatment repeats every 4 weeks (28 days) for up to 24 months or 26 courses, whichever occurs first, in the absence of disease progression or unacceptable toxicity.
Genetic analysis of familial breast and ovarian cancer indicates that BRCA1 is a tumor suppressor gene. The BRCA1 gene encodes a 190 kDa protein with sequence homology and biochemical analogy to the granin family of proteins. Granins are secreted from endocrine cells via the regulated secretory pathway and are proteolytically cleaved to yield biologically active peptides. BRCA1 protein localizes to secretory vesicles, and was demonstrated to be secreted. Gene transfer of BRCA1 inhibits growth and tumorigenesis of breast and ovarian cancer cells, but not colon or lung cancer cells or fibroblasts, suggesting that BRCA1 encodes a tissue-specific growth inhibitor. Thus, BRCA1 is a secreted growth inhibitor and functions by a mechanism not previously described for tumor suppressor genes. The BRCA2 breast and ovarian cancer gene encodes a protein that also includes a granin region, indicating that the BRCA2 protein is also a secreted tumor suppressor. Therapeutic methods using the BRCA1 and BRCA proteins and genes are also described. A method of screening for the receptors of the BRCA1 protein and BRCA2 proteins is also described.
Patients receiving accelerated Invisalign therapy will be instructed to wear each aligner 24 hours day. Patients will be permitted to progress to the subsequent aligner after 4 days of compliant aligner wear.
In this study, the liver metastases were treated with Cyberknife stereotactic radiotherapy.Using multimodal image fusion to outline the target area.According to the volume, location, organ function and other factors, the dosage of radiotherapy was determined. The range of BED value of radiotherapy was 90-120 when the distance between the tumor and gastrointestinal tract was more than 5 mm (alpha/beta=10) and 70-90 when the distance between the tumor and gastrointestinal tract was less than 5 mm (alpha/beta=10).
This is an online randomized controlled trial in which researchers will use a survey company to recruit participants to an online survey. In the study, participants will be randomized to 1 of 6 labeling arms: 1) a QR code on all items (control); 2) High Climate Impact label; 3) High Climate Impact Warning label; 4) Climate Grade label; 5) Climate Grade label also displaying full range of possible grades; 6) Estimated Environmental Cost label. Labels will only appear alongside main menu items and will be assigned using thresholds for greenhouse gas emissions set a priori in kilograms of CO2 equivalent per kilogram of food. Each participant will view a menu based on a real-world restaurant with one of the 6 labels shown on applicable menu items, select the menu item they would like, then respond to survey questions about each label.

For dichotomous outcomes, the investigators will directly estimate the probability ratio using Poisson regression with a robust error variance, regressing the outcome on indicators for experimental condition. For continuous outcomes, the investigators will use linear regression models, regressing the outcome on indicators for experimental condition. A critical alpha 0.05 will be used, and statistical tests will be two-tailed. Investigators will compare all experimental label conditions to the control label, then compare each experimental label to each other using pairwise comparisons.
* At the initial visit, participants will have a complete examination of their skin, hair and nails. We will also test muscle strength and movement by moving the participant's arms, legs and neck. Photographs will be taken of the skin, hair and nails of they are abnormal. Blood tests will be done to check the liver and blood cell count. The participant and their legal guardian will answer questions about how the participant feels and about their health.
* Participants will then be scheduled for follow up visits at 3 months, 6 months, and 12 months. At each subsequent visit the following will be done: A complete examination of the skin, hair and nails; a test of muscle strength; photographs will be repeated; blood tests to check liver and blood cell counts; and questions about how the participant feels and about their health.
Subjects with different age and BMI will be included. 1) 20 subjects aged 20-29 years with normal body weight (18.5 ≤BMI\<24kg/m2); 2) 40 20 subjects aged 30-70 49 years with normal body weight (18.5 ≤ BMI\<24kg/m2); 3) 40 20 subjects aged 30-70 49 years with overweight or obesity (BMI\<24kg/m2).); 4) 20 subjects aged 50-70 years with normal body weight (18.5 ≤ BMI\<24kg/m2); 5) 20 subjects aged 30-49 years with overweight or obesity (BMI\<24kg/m2); 6) 20 subjects aged 30-70 years with MetS.
BACKGROUND: Cell-free DNA (cfDNA) is a source for liquid biopsy used for cancer diagnosis, therapy selection, and disease monitoring due to its non-invasive nature and ease of extraction. However, cfDNA also participates in cancer development and progression by horizontal transfer. In humans, cfDNA circulates complexed with extracellular vesicles (EV) and macromolecular complexes such as nucleosomes, lipids, and serum proteins. The present study aimed to demonstrate whether cfDNA not associated with EV induces cell transformation and tumorigenesis.
METHODS: Supernatant of the SW480 human colon cancer cell line was processed by ultracentrifugation to obtain a soluble fraction (SF) and a fraction associated with EV (EVF). Primary murine embryonic fibroblast cells (NIH3T3) underwent passive transfection with these fractions, and cell proliferation, cell cycle, apoptosis, cell transformation, and tumorigenic assays were performed. Next, cfDNA was analyzed by electronic microscopy, and horizontal transfer was assessed by human mutant KRAS in recipient cells via PCR and recipient cell internalization via fluorescence microscopy.
RESULTS: The results showed that the SF but not the EVF of cfDNA induced proliferative and antiapoptotic effects, cell transformation, and tumorigenesis in nude mice, which were reduced by digestion with DNAse I and proteinase K. These effects were associated with horizontal DNA transfer and cfDNA internalization into recipient cells.
CONCLUSIONS: The results suggest pro-tumorigenic effects of cfDNA in the SF that can be offset by enzyme treatment. Further exploration of the horizontal tumor progression phenomenon mediated by cfDNA is needed to determine whether its manipulation may play a role in cancer therapy.
BACKGROUND: Takayasu Arteritis (TA) is an immune mediated arteritis causing inflammation of the aorta and its branches, which can result in aortic aneurysms. Our aim is to describe the outcome of surgical management in these patients who presented with Thoracoabdominal aortic aneurysm (TAAA).
METHODS: Between 2003 and 2023, 40 TA patients with TAAA underwent operative repair.
RESULTS: There were 24 females and 16 males, in the age group of 19-53 years, with hypertension in 20 patients. Raised Erythrocyte sedimentation Rate was present in 13 patients. According to Crawford classification, there were 2 patients with type I, 2 with type II, 17 with type III, 12 patients with type IV and 7 with type V aneurysm. Multiple steno-occlusive lesions of aortic branches were present in 21 patients, with majority affecting the renal artery. Femoral Artery Femoral Vein Partial cardiopulmonary bypass was used for types I, II, III and V. Separate bypass to visceral branches was done in eight patients, of whom five had multiple bypasses and three patients only had renal bypass. Twelve patients underwent reimplantation of branches, out of which nine had multiple vessel reimplantation. Four patients underwent staged repair of the aneurysm, which included visceral debranching in the first day, followed by repair of the aneurysm in the next day. In the immediate postoperative period, ten patients developed acute kidney injury and two required dialysis. Other morbidities included acute respiratory distress syndrome (ARDS), spinal cord dysfunction, bleeding, and wound complications. Three patients expired in the immediate postoperative period. Mean duration of intensive care unit stay was 4.1 days and hospital stay was 12.7 days. Comparison of disease activity with morbidity and mortality was statistically insignificant. Patients were on follow-up for a range of 6 months to 14 years and median follow-up of 25 months. Over this time period four patients expired and four developed anastomotic pseudoaneurysm requiring intervention. On comparing the disease activity at the time of surgery with the long-term arteritis related complications that required intervention, the P value was 0.653 and hence statistically not significant. The 10-year survival rate is 84.4%.
CONCLUSIONS: Surgical repair has good and satisfactory outcome, with low early and late mortality rates. Progression of disease can occur at any stage of the disease, hence indicating the need for long term follow-up and frequent imaging.
BACKGROUND: Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder that is characterized by quotidian fevers, arthritis, and an evanescent rash. Occurrence of concurrent thrombotic microangiopathy (TMA) in AOSD is rare. The treatment aspects of TMA in AOSD are actively being debated.
METHODS: Medline search using MeSH terms and snowballing yielded a total of 29 articles with co-occurrence of AOSD and thrombotic thrombocytopenic purpura (TTP) including our own. Pooled data were synthesized for descriptive analysis.
RESULTS: Median age was 35 years with a majority of females (68.96%). A majority of these studies/patients were either Asian (34.48%) or Caucasian (31.03%). Concurrent TMA at the time of AOSD diagnosis was seen in 65.51% patients. Only 3/29 patients had ADAMTS13 level less than 10%, consistent with TTP and 3/29 were diagnosed with hemolytic uremic syndrome (HUS). The remainder were diagnosed clinically. Complication rate was high, and 15/29 (51.72%) patients died or had permanent neurological/renal/vision/gangrenous complications. Median and mean ferritin peak was observed to be higher (7458 and 12 349, respectively) in patients who either died/had partial remission, compared to those who had complete response (3257 and 10 899, respectively), p = .829.
CONCLUSIONS: A majority of patients with AOSD-associated TMA either died or had permanent complications. TMA was diagnosed alongside AOSD in 65% patients, while the rest developed TMA during the course of their disease. Blurred vision may precede TMA and could help risk-stratify high-risk AOSD patients clinically. Glycosylated ferritin remains low several weeks to months after disease remission and may be used to monitor severity of disease process. Further studies are necessary to confirm the existing vascular endothelial growth factor hypothesis in AOSD-associated TMA.
Mulberry (Morus alba L) fruit is traditionally used in Chinese medicine and has several beneficial effects, such as hypoglycemic, hypolipidemic, and anti-oxidative effects. We previously developed the synbiotic mulberry (SM) containing probiotic Lactobacilli, prebiotic inulin, and mulberry powder. In food supplement development, toxicity is the most important criterion in food and drug regulations before commercialization. Thus, this study aimed to investigate the subchronic toxicity of SM in male and female Wistar rats to evaluate its biosafety. The subchronic toxicity study was conducted by daily oral administration of SM at doses of 250, 500, and 1000 mg/kgBW for 90 days. Male and female rats were evaluated for body weight, organ coefficients, biochemical and hematological parameters, and vital organ histology. The results showed no mortality or toxic changes in the subchronic toxicity study. These results suggested that no observed adverse effect level (NOAEL) of SM in male and female rats has been considered at 1000 mg/kgBW for subchronic toxicity study.
Plant metabolites from natural product extracts offer unique advantages against carcinogenesis in the development of drugs. The target-based virtual screening from food-derived compounds represents a promising approach for tumor therapy. In this study, we performed virtual screening to target the presumed inhibitor-binding pocket and identified a highly potent Kv10.1 inhibitor, liensinine (Lien), which can inhibit the channel in a dose-dependent way with an IC50 of 0.24 ± 0.07 μM. Combining molecular dynamics simulations with mutagenesis experiments, our data show that Lien interacts with Kv10.1 by binding with Y539, T543, D551, E553, and H601 in the C-linker domain of Kv10.1. In addition, the interaction of sequence alignment and 3D structural modeling revealed differences between the C-linker domain of the Kv10.1 channel and the Kv11.1 channel. Furthermore, antitumor experiments revealed that Lien suppresses the proliferation and migration of HCC both in vitro and in vivo. In summary, the food-derived compound, Lien, may serve as a lead compound for antihepatoma therapeutic drugs targeting Kv10.1.
Eligible subjects will be randomized to receive a single dose of Treatment A (GR37547 500 mg tablet) followed by Treatment B (ciprofloxacin 500 mg reference tablet) administered orally on Day 1 in each treatment period. The washout period will be of at least 7 days and not more than 14 days.
BACKGROUND: Dedifferentiated liposarcoma of the extremities (DDL-E) is rare in comparison to that of the retroperitoneum. Its clinical features and surgical principle for resection margins at the dedifferentiated and the well-differentiated components are yet to be elucidated.
METHODS: This retrospective multi-center study examined patients diagnosed with DDL-E from August 2004 to May 2023 at 5 sarcoma centers. Clinical features, oncologic outcomes, and prognostic factors were analyzed.
RESULTS: A total of 107 patients were reviewed. The 5-year local recurrence free survival (LRFS), metastasis-free survival (MFS) and disease specific survival (DSS) were 84.7%, 78.6%, and 87.8%, respectively. Other primary malignancies and extrapulmonary metastasis were observed in 27 and 4 patients, respectively. The independent risk factor for local recurrence was R1/2 margin at the dedifferentiated component of the tumor. Metastasis was associated with tumor size in univariate analysis. The independent risk factor for DSS was tumor grade. Previous unplanned excision, de novo presentation, tumor depth, absence of the well-differentiated component, infiltrative border, R1/2 margin at the well-differentiated component were not associated with oncologic outcomes.
CONCLUSIONS: This is the largest study examining DDL-E to-date. Localized DDL-E has low potential for metastasis and carries an excellent prognosis. Other primary malignancy and extrapulmonary metastasis are more frequent in DDL-E, thus close monitoring of other sites during follow-up is recommended. While wide resection margin is the standard surgical approach for DDL-E, further investigation into moderated wide resection margin at the well-differentiated component is warranted.
Participants randomized to this group will undergo usual care in the Critical Care Trauma Centre. Temperature will be monitored as per standard of care. Participants will be followed post-discharge and will undergo cognitive assessments at 3 and 6 months.
This is a parallel, quadruple-blind, randomized controlled trial to determine the effects of double fortification (iron and zinc) in synbiotic milk (containing 7 billion CFU L.plantarum Dad13 and 4 g fructooligosaccharides) on the gut microbiota composition, body height and weight, blood zinc and hemoglobin level, and cognitive level in under 5 years stunted children subjects. The duration of the study is 4 months, including a 2-week pre test and informed consent before randomization of subjects into treatment or control group, a 12-week intervention period, and a 2-week post test after the end of intervention. During the intervention period, subjects will be instructed to take 100 ml of fortified synbiotic milk or non-fortified synbiotic milk per day. They will also be asked to document consumed milk, any unusual symptoms or side effects of treatment. Diet will be monitored via 24-h dietary recalls and SQ-FFQ before and after treatment respectively. Changes in the gut microbiota composition will be determined by measuring bacterial population levels (Bifidobacteria, Lactobacillus, Enterobacteria, Prevotella, and Bacteroides) in stool sampled collected at baseline and 12 weeks by qPCR. Metabolic markers (calprotectin, hemoglobin, and zinc level) will be measured at baseline and 12-weeks in serum and plasma using biochemical and immuno-assay. Changes in the cognitive level, height for age Z-score collected at baseline and 12 weeks using Bayley Scales of Infant Development, 2nd Edition .
All participants enrolled in the trial will receive supervised remote-based resistance exercise training. The exercises will be performed with the use of Therabands and will include 8-10 exercises performed for 1 set of 15 repetitions, performed 3 days per week for 24 weeks.