anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Inulin, an increasingly studied dietary fiber, alters intestinal microbiota. The aim of this study was to assess whether inulin decreases intestinal colonization by multidrug resistant E. coli and to investigate its potential mechanisms of action. Mice with amoxicillin-induced intestinal dysbiosis mice were inoculated with extended spectrum beta-lactamase producing E. coli (ESBL-E. coli). The combination of inulin and pantoprazole (IP) significantly reduced ESBL-E. coli fecal titers, whereas pantoprazole alone did not and inulin had a delayed and limited effect. Fecal microbiome was assessed using shotgun metagenomic sequencing and qPCR. The efficacy of IP was predicted by increased abundance of 74 taxa, including two species of Adlercreutzia. Preventive treatments with A. caecimuris or A. muris also reduced ESBL-E. coli fecal titers. Fecal microbiota of mice effectively treated by IP was enriched in genes involved in inulin catabolism, production of propionate and expression of beta-lactamases. They also had increased beta-lactamase activity and decreased amoxicillin concentration. These results suggest that IP act through production of propionate and degradation of amoxicillin by the microbiota. The combination of pantoprazole and inulin is a potential treatment of intestinal colonization by multidrug-resistant E. coli. The ability of prebiotics to promote propionate and/or beta-lactamase producing bacteria may be used as a screening tool to identify potential treatments of intestinal colonization by multidrug resistant Enterobacterales.
BACKGROUND AND AIMS: Vascular injury-induced endothelium-denudation and profound vascular smooth muscle cells (VSMCs) proliferation and dis-regulated apoptosis lead to post-angioplasty restenosis. Coptisine (CTS), an isoquinoline alkaloid, has multiple beneficial effects on the cardiovascular system. Recent studies identified it selectively inhibits VSMCs proliferation. However, its effects on neointimal hyperplasia, re-endothelialization, and the underlying mechanisms are still unclear.
METHODS: Cell viability was assayed by 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and cell counting kit-8 (CCK-8). Cell proliferation and apoptosis were measured by flow cytometry and immunofluorescence of Ki67 and TUNEL. Quantitative phosphoproteomics (QPP) was employed to screen CTS-responsive phosphor-sites in the key regulators of cell proliferation and apoptosis. Neointimal hyperplasia was induced by balloon injury of rat left carotid artery (LCA). Adenoviral gene transfer was conducted in both cultured cells and LCA. Re-endothelialization was evaluated by Evan's blue staining of LCA.
RESULTS: 1) CTS had strong anti-proliferative and pro-apoptotic effects in cultured rat VSMCs, with the EC50 4∼10-folds lower than that in endothelial cells (ECs). 2) Rats administered with CTS, either locally to LCA's periadventitial space or orally, demonstrated a potently inhibited balloon injury-induced neointimal hyperplasia, but had no delaying effect on re-endothelialization. 3) The QPP results revealed that the phosphorylation levels of Pak1S144/S203, Pak2S20/S197, Erk1T202/Y204, Erk2T185/Y187, and BadS136 were significantly decreased in VSMCs by CTS. 4) Adenoviral expression of phosphomimetic mutants Pak1D144/D203/Pak2D20/D197 enhanced Pak1/2 activities, stimulated the downstream pErk1T202/Y204/pErk2T185/Y187/pErk3S189/pBadS136, attenuated CTS-mediated inhibition of VSMCs proliferation and promotion of apoptosis in vitro, and potentiated neointimal hyperplasia in vivo. 5) Adenoviral expression of phosphoresistant mutants Pak1A144/A203/Pak2A20/A197 inactivated Pak1/2 and totally simulated the inhibitory effects of CTS on platelet-derived growth factor (PDGF)-stimulated VSMCs proliferation and PDGF-inhibited apoptosis in vitro and neointimal hyperplasia in vivo. 6) LCA injury significantly enhanced the endogenous phosphorylation levels of all but pBadS136. CTS markedly attenuated all the enhanced levels.
CONCLUSIONS: These results indicate that CTS is a promising medicine for prevention of post-angioplasty restenosis without adverse impact on re-endothelialization. CTS-directed suppression of pPak1S144/S203/pPak2S20/S197 and the subsequent effects on downstream pErk1T202/Y204/pErk2T185/Y187/pErk3S189 and pBadS136 underline its mechanisms of inhibition of VSMCs proliferation and stimulation of apoptosis. Therefore, the phosphor-sites of Pak1S144/S203/Pak2S20/S197 constitute a potential drug-screening target for fighting neointimal hyperplasia restenosis.
PURPOSE:To increase the adsorption capacity for phosphoric acid ion by depositing the powder which is obtained by the drying of the cake obtained by meas of filtering the hydrated oxides of rare earth elements on a porous carrier or depositing the powder with organic high molecular material on the carrier. CONSTITUTION:An adsorbent of phosphoric acid ion is formed as a molded body for deposition which consists of the hydrated oxides of rare earth elements and the preferably the above-mentioned hydrated oxides are deposited with organic high molecular material and furthermore the above-mentioned hydrated oxides are preferably deposited with organic high molecular material of calcium adsorption type hydrated oxides adsorbed with Ca ion. The hydrated oxides of rare earth elements are the compd. obtained by the hydroxylation of the oxides of rare earth elements and hydrochloric acid. As the rare earth elements, La, Ce and Y are preferable since the adsorption quantities are large and especially Ce is preferable because the solubility is minimum. The average grain size of granules of rare earth hydrated oxides is preferably 0.01-1mu as primary grain size.
BACKGROUND: Pretreatment levels of serum carcinoembryonic antigen (CEA) and perineural invasion (PNI) are related to poor prognosis in colon cancer. We analyzed the CEA and PNI (defined as incorporation of carcinoembryonic antigen and perineural invasion (CP)-stage), which are included in the Tumor-Node-Metastasis (TNM) staging system of the American Joint Committee on Cancer (AJCC), and evaluated the survival prognosis of patients treated with surgery in I-III stage colon carcinoma.
MATERIALS AND METHODS: We employed a retrospective study for eligible colon carcinoma patients obtained from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. Kaplan-Meier curve and Multivariate Cox regression analysis were used to analyze different TNM-CP stages for the cancer-specific survival (CSS) probabilities in colon cancer.
RESULT: In our study, CEA levels and PNI were significant prognostic factors (p < 0.05), and the newly proposed CP-stage was an independent prognostic index in stage I-III colon carcinoma after surgery. Multivariate Cox regression analyses indicated that CP1-stage was related to a 63.9% increased risk of cancer-specific mortality (hazard ratio (HR): 1.639, 95% confidence interval (CI): 1.544-1.739, p < 0.001), compared with CP0-stage in colon cancer. In respective TNM stages, the CP0-stage had an advantage over the CP1-stage for CSS (p < 0.001). Moreover, CP1-stage patients with node-negative colon cancer were contacted with similar or worse survival in comparison to CP0-stage patients with node-positive.
CONCLUSION: For postoperative patients with stage I-III colon cancer, our study indicated that the CP stage is a significant prognostic factor for CSS, which deserves more clinical attention. It's worth noting that including the CP stage in the AJCC TNM staging system of colon carcinoma is beneficial to the survival prediction and clinical treatment.
The sample size calculation was completed based on an effect size of 0.65 (power = 0.80; 2-tailed; α= 0.05). Assuming a 5% attrition rate, a total of 56 residents (28 people in a control group and 28 people in the intervention group) will be recruited. A block randomization design using a number generator to conceal the randomization sequence will be used to assign participants' units to the intervention or control groups. Block randomization was conducted to comply with COVID-19 restrictions. The investigators will attempt to recruit equal numbers of men and women with a range of mobility requirements (i.e., ambulate independently, using gait aids such as canes or walkers). In addition, a mix of approximately 5-10 LTC staff and/or residents' family members will be recruited at the end of the trial to conduct semi-structured interviews to understand the acceptability of the technology, design, usability and enjoyment, potential facilitators and barriers to exergame technology.
Neuro-inflammation involves distinct alterations of microglial phenotypes, containing nocuous pro-inflammatory M1-phenotype and neuroprotective anti-inflammatory M-phenotype. Currently, there is no effective treatment for modulating such alterations. M1/M2 marker of primary microglia influenced by Melatonin were detected via qPCR. Functional activities were explored by western blotting, luciferase activity, EMSA, and ChIP assay. Structure interaction was assessed by molecular docking and LIGPLOT analysis. ER-stress detection was examined by ultrastructure TEM, calapin activity, and ERSE assay. The functional neurobehavioral evaluations were used for investigation of Melatonin on the neuroinflammation in vivo. Melatonin had targeted on Peroxisome Proliferator Activated Receptor Delta (PPARδ) activity, boosted LPS-stimulated alterations in polarization from the M1 to the M2 phenotype, and thereby inhibited NFκB-IKKβ activation in primary microglia. The PPARδ agonist L-165,041 or over-expression of PPARδ plasmid (ov-PPARδ) showed similar results. Molecular docking screening, dynamic simulation approaches, and biological studies of Melatonin showed that the activated site was located at PPARδ (phospho-Thr256-PPARδ). Activated microglia had lowered PPARδ activity as well as the downstream SIRT1 formation via enhancing ER-stress. Melatonin, PPARδ agonist and ov-PPARδ all effectively reversed the above-mentioned effects. Melatonin blocked ER-stress by regulating calapin activity and expression in LPS-activated microglia. Additionally, Melatonin or L-165,041 ameliorated the neurobehavioral deficits in LPS-aggravated neuroinflammatory mice through blocking microglia activities, and also promoted phenotype changes to M2-predominant microglia. Melatonin suppressed neuro-inflammation in vitro and in vivo by tuning microglial activation through the ER-stress-dependent PPARδ/SIRT1 signaling cascade. This treatment strategy is an encouraging pharmacological approach for the remedy of neuro-inflammation associated disorders.
The invention provides a substantially pure Prolactin Releasing Peptide (PrRP) functional analog which suppresses absence seizures in a mammal, and related pharmaceutical compositions. The invention also provides a method of controlling absence seizures in a mammal, by administering to a mammal susceptible to absence seizures an effective amount of PrRP or a PrRP functional analog. Also provided are methods of identifying a compound that modulates AMPA receptor signaling in a mammal, by providing a compound that is a PrRP or PrRP functional analog, and determining the ability of the compound to modulate AMPA receptor signaling. The invention also provides methods of identifying a compound for controlling absence seizures in a mammal, by providing a compound that is a PrRP or PrRP functional analog, and determining the ability of the compound to control absence seizures in a mammal. Also provided are pharmaceutical compositions for controlling absence seizures in a mamma. The compositions and related methods contain a compound identified by the methods of the invention as a compound that modulates AMPA receptor signaling or as a compound that controls absence seizures.
In-depth education session regarding the effects of dehydration, the performance benefits of proper hydration, and how to properly hydrate before, during, and after activity. Pre-practice urine specific gravity (USG), pre- and post-practice body mass, thirst scale measures. Provided a standard amount of bottled water to drink the evening prior (1 liter) and in the two hours before practice (20 oz). Fluid intake will be recorded in an intake log. Subjects will be permitted to eat or drink whatever they like in addition to the prescribed fluid. Fluid intake during practice (whatever the team is drinking).
A method of treating a mammalian subject having hematologic, non-tumorous cancer cells is disclosed. The method comprises the steps of: (A) administering to such a mammalian subject a therapeutically effective amount of a halogenated xanthene, a pharmaceutically acceptable salt or a C1-C4 alkyl ester thereof as a first cancer cytotoxic agent dissolved or dispersed in a pharmaceutically acceptable aqueous medium. The mammalian subject is maintained for a period of time sufficient to induce death of hematologic, non-tumorous cancer cells. A contemplated administration is typically repeated. A contemplated treatment method can also be carried out in conjunction with administration to said mammalian subject of a second therapeutically effective amount of a second, differently-acting cancer cytotoxic agent dissolved or dispersed in a pharmaceutically acceptable medium. The second cancer cytotoxic agent can be a small molecule or an intact antibody or paratope-containing portion thereof.
During a sepsis infection, the lung is extremely susceptible to damage. A condition known as acute respiratory distress syndrome (ARDS) may develop in extreme circumstances. The primary objective of this research is to identify important genes that are related with both sepsis and lung injury. These genes have the potential to act as novel biomarkers in the investigation of sepsis-induced lung injury prevention strategies. It was possible to download from GEO data both the sepsis-related dataset (GSE64457) and the lung injury-related dataset (GSE40839). In the GSE64457 dataset, using the "limma" package in R revealed 429 differentially expressed genes (DEGs) with logFC values more than or equal to -1 and p values <0.05. There were 266 genes that were up-regulated and 163 genes that were down-regulated. Through the use of Gene Ontology (GO), it was discovered that the majority of the DEGs were associated with the inflammatory response (BP terms), a particular granule lumen (CC terms), and protein binding (MF terms). By doing a pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG), researchers were able to identify DEGs that were mostly associated with the NOD-like receptor signalling pathway, the TNF signalling pathway, and Epstein-Barr virus infection. Within the GSE40839 dataset, Weighted Gene Co-Expression Network Analysis (WGCNA) yielded a total of 7 modules, from which it was possible to screen out 2 critical modules and 693 key genes. The important genes and DEGs were both subjected to a Venn analysis. Finally, 14 genes that overlapped (ARL4A, LAIR1, MTHFD2, TSPAN13, DUSP6, PECR, CBS, TES, ASNS, SYNE1, FGF13, LCN2, KLF10, BCAT1) were closely associated to the incidence and development of sepsis-induced lung injury. This indicates that these genes are the essential genes to avoid the occurrence of sepsis-induced lung injury. This study provides novel strategies for preventing lung harm brought on by sepsis.
Background : The treatment strategy of early nutritional support after cardiac surgery has gradually been adopted. However, there are no scientific guidelines for the timing and specific programs of early nutritional support. Methods: A retrospective, single-center analysis (2021-2023) was carried out including elderly patients who were admitted for valvular heart disease and received open-heart valve replacement surgery. We designated patients who started the optimized nutritional support after surgery as the optimized enteral nutritional support strategy TN (EN) group and those who received traditional nutritional support as the traditional nutritional support strategy (TN) group. The nutritional and immune indexes, postoperative complications, length of hospital stay, and hospitalization cost of the two groups were compared and analyzed. Results: We identified 378 eligible patients, comprising 193 (51%) patients in the EN group and 185 (49%) patients in the TN group. There was no significant difference in hospital mortality between the two groups, but the proportion of nosocomial pneumonia was significantly lower in the EN group than in the TN group ( P < 0.001). In the Poisson regression analysis, EN was not associated with an increase in gastrointestinal complications ( P = 0.549). The EN group also seemed to have shorter hospital stays and lower hospitalization expenses ( P < 0.001). In the comparison of postoperative gastrointestinal complications, fewer patients experienced diarrhea ( P = 0.021) and abdominal distension ( P = 0.033) in the EN group compared with the TN group. Conclusion: The optimal nutritional support strategy could effectively improve the clinical outcome of high-risk patients with valvular heart disease.
Lung cancer is a leading cause of cancer-related mortality globally, with a dismal 5-year survival rate, particularly for Lung Adenocarcinoma (LUAD). Mechanical changes within the tumor microenvironment, such as extracellular matrix (ECM) remodeling and fibroblast activity, play pivotal roles in cancer progression and metastasis. However, the specific impact of the basement membrane (BM) on the mechanical characteristics of LUAD remains unclear. This study aims to identify BM genes influencing internal mechanical stress in tumors, elucidating their effects on LUAD metastasis and therapy resistance, and exploring strategies to counteract these effects. Using Matrigel overlay and Transwell assays, we found that mechanical stress, mimicked by matrix application, augmented LUAD cell migration and invasion, correlating with ECM alterations and activation of the epithelial-mesenchymal transition (EMT) pathway. Employing machine learning, we developed the SVM_Score model based on relevant BM genes, which accurately predicted LUAD patient prognosis and EMT propensity across multiple datasets. Lower SVM_Scores were associated with worse survival outcomes, elevated cancer-related pathways, increased Tumor Mutation Burden, and higher internal mechanical stress in LUAD tissues. Notably, the SVM_Score was closely linked to COL5A1 expression in myofibroblasts, a key marker of mechanical stress. High COL5A1 expression from myofibroblasts promoted tumor invasiveness and EMT pathway activation in LUAD cells. Additionally, treatment with Sorafenib, which targets COL5A1 secretion, attenuated the tumor-promoting effects of myofibroblast-derived COL5A1, inhibiting LUAD cell proliferation, migration, and enhancing chemosensitivity. In conclusion, this study elucidates the complex interplay between mechanical stress, ECM alterations, and LUAD progression. The SVM_Score emerges as a robust prognostic tool reflecting tumor mechanical characteristics, while Sorafenib intervention targeting COL5A1 secretion presents a promising therapeutic strategy to mitigate LUAD aggressiveness. These findings deepen our understanding of the biomechanical aspects of LUAD and offer insights for future research and clinical applications.
The body of a human has a vast array of microorganisms termed the microbiome that impacts almost every function of the body. Gene-environment interactions play a major role in making us susceptible to cancer and the microbiome is such an environmental factor that we are exposed to from the very beginning of our lives to the very end. Increasing pieces of evidence are pointing towards an association of cancer and the microbiome. The bacteria inside our body might help us prevent some cancers as well as may increase the risk of carcinogenesis and treatment responses. Many studies are suggesting that tinkering with the microbiome might be a new way to treat and prevent many kinds of cancer. Although information on the roles of the microbiome in carcinogenesis is scant and almost no direct links have been found between these two yet. This review offers some of the recent evidences of the association between cancer and the microbiome, discuss the impact of gut bacteria on cancer and provide a detailed discussion on gut microbiota mediated therapeutic approaches with a special focus on Hepatocellular Carcinoma. The implementation of the new knowledge discovered in this subject calls for a great deal of research.
The reduced oxygen breathing device will be set to deliver a gas mixture with15% oxygen. (Equivalent to the partial pressure of oxygen at 2,438 meters.) The subject will perform CPR while breathing through mask and tubing that is connected to the device.
Each tablet of carbidopa-levodopa in this study will be equivalent to half of a standard carbidopa-levodopa 25/100mg tablet. Participants will take one tablet three times a day for the first week of the study period, increasing to two tablets three times a day for the remainder of the study period.
Parents of infants assigned to the Family Integrated Care (mFI-Care) intervention will be treated as primary caregivers for their infants and participate in daily medical rounds, with mFI-Care-trained nurses serving as teachers and coaches. Parent training on the Canadian FI-Care Parent Curriculum will be provided during small group sessions facilitated by the study team. Parents will receive peer support from mFI-Care-trained alumni parents and can interact with other mFI-Care parents through the We3Health App secure online parent forum. mFI-Care parents will be expected to track time spent with their infant; record infant activity, feeds and output; track learning and skills acquisition; and keep a journal of the NICU experience using the We3Health app.
With the combination with nivolumab, a cycle of study treatment will be defined as 28 days. ATG-017 is planned initially to be continuously given 28 days in each cycle. ATG-017 dosing schedule in combination therapy will follow a similar dose escalation principle as with monotherapy but starting at 5 mg BID. Nivolumab will be given at fixed dosing, 480 mg Q4W, on D1 of each cycle.
Renal Insufficiency: Single 300 mg zonisamide doses were administered to three groups of volunteers. Group 1 was a healthy group with a creatinine clearance ranging from 70 to 152 mL/min. Group 2 and Group 3 had creatinine clearances ranging from 14.5 to 59 mL/min and 10 to 20 mL/min, respectively. Zonisamide renal clearance decreased with decreasing renal function (3.42, 2.50, 2.23 mL/min, respectively). Marked renal impairment (creatinine clearance < 20 mL/min) was associated with an increase in zonisamide AUC of 35% (see DOSAGE AND ADMINISTRATION section).

Hepatic Disease: The pharmacokinetics of zonisamide in patients with impaired liver function have not been studied (see DOSAGE AND ADMINISTRATION section).

Age: The pharmacokinetics of a 300 mg single dose of zonisamide was similar in young (mean age 28 years) and elderly subjects (mean age 69 years).

Gender and Race: Information on the effect of gender and race on the pharmacokinetics of zonisamide is not available.

Interactions of Zonisamide with Other Antiepilepsy Drugs (AEDs): 

Concurrent medication with drugs that either induce or inhibit CYP3A4 may alter serum concentrations of zonisamide. Concomitant administration of phenytoin and carbamazepine increases zonisamide plasma clearance from 0.30 to 0.35 mL/min/kg to 0.35 to 0.5 mL/min/kg. The half-life of zonisamide is decreased to 27 hours by phenytoin, to 38 hours by phenobarbital and carbamazepine, and to 46 hours by valproate. Plasma protein binding of phenytoin and carbamazepine was not affected by zonisamide administration (see PRECAUTIONS, Drug Interactions subsection).