anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
This is a first-in-human Phase 1a/1b, multicenter, open-label, dose-escalation, dose and schedule optimization, and expansion study of TPST-1495 as a single agent and in combination with pembrolizumab to determine its MTD, safety, tolerability, pharmacokinetics (PD), pharmacodynamics (PK) and preliminary anti-tumor activity in subjects with advanced solid tumors. Subjects with all histologic types of solid tumors are eligible for the study. However, the preferred tumor types for enrollment are colorectal cancer (CRC), non-small cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN), urothelial cancer, endometrial cancer, and gastroesophageal junction (GEJ) or gastric adenocarcinoma. Tumor prostaglandin production and downstream signaling in both tumor cells and other cell types, including immune suppressive cell population in the tumor microenvironment, is thought to be a principal driver of progression in each of these selected malignancies. To be eligible, subjects must have no remaining standard therapy known to confer clinical benefit.

The study is composed of 3 stages. The Dose-Escalation stage will determine the MTD of single-agent TPST-1495 administered twice a day (BID). The Schedule and Dose Optimization stage will evaluate alternative TPST-1495 single-agent administration schedules and determine an RP2D for the selected schedule. This arm will also evaluate TPST-1495 in combination with pembrolizumab. The Expansion stage will evaluate the activity of TPST-1495 as a single agent and in combination with pembrolizumab at the selected schedule and dose in disease-specific cohorts and in a basket cohort in subjects selected for an activating mutation in PIK3Ca.
To induce anesthesia, 1% propofol 1.5-2.5mg/kg is used with remifentanil (Ce of 1-4ng/ml) by target-controlled infusion (TCI). After patient loses consciousness, anesthesia is maintained through the inhalation of sevoflurane between 1-2 minimum alveolar concentrations (MAC). Remifentanil is titrated to maintain the bispectral index (BIS) between 40 and 60 to achieve appropriate anesthetic depth during general anesthesia.
PURPOSE: Black women experience the highest breast cancer mortality rate compared with women of other racial/ethnic groups. To gain a deeper understanding of breast cancer heterogeneity across diverse populations, we examined a VEGF-hypoxia gene expression signature in breast tumors from women of diverse ancestry.
EXPERIMENTAL DESIGN: We developed a NanoString nCounter gene expression panel and applied it to breast tumors from Nigeria (n = 182) and the University of Chicago (Chicago, IL; n = 161). We also analyzed RNA sequencing data from Nigeria (n = 84) and The Cancer Genome Atlas (TCGA) datasets (n = 863). Patient prognosis was analyzed using multiple datasets.
RESULTS: The VEGF-hypoxia signature was highest in the basal-like subtype compared with other subtypes, with greater expression in Black women compared with White women. In TCGA dataset, necrotic breast tumors had higher scores for the VEGF-hypoxia signature compared with non-necrosis tumors (P < 0.001), with the highest proportion in the basal-like subtype. Furthermore, necrotic breast tumors have higher scores for the proliferation signature, suggesting an interaction between the VEGF-hypoxia signature, proliferation, and necrosis. T-cell gene expression signatures also correlated with the VEGF-hypoxia signature when testing all tumors in TCGA dataset. Finally, we found a significant association of the VEGF-hypoxia profile with poor outcomes when using all patients in the METABRIC (P < 0.0001) and SCAN-B datasets (P = 0.002).
CONCLUSIONS: These data provide further evidence for breast cancer heterogeneity across diverse populations and molecular subtypes. Interventions selectively targeting VEGF-hypoxia and the immune microenvironment have the potential to improve overall survival in aggressive breast cancers that disproportionately impact Black women in the African Diaspora.
Coronary revascularization has matured as a field since coronary artery bypass grafting (CABG) was first developed over 50 years ago, with diagnostic and treatment methods have advanced dramatically. CABG remains the standard of care for obstructive coronary artery disease, particularly for patients with multivessel disease or diabetes. (1) Despite significant therapeutic advances, patients with chronic heart failure (HF) remain at high risk for HF progression and death. Sacubitril/valsartan (previously known as LCZ696) is a first-in-class medicine that contains a neprilysin (NEP) inhibitor (sacubitril) and an angiotensin II (Ang-II) receptor blocker (valsartan). NEP is an endopeptidase that metabolizes different vasoactive peptides including natriuretic peptides, bradykinin and Ang-II. In consequence, its inhibition increases mainly the levels of both, natriuretic peptides (promoting diuresis, natriuresis and vasodilatation) and Ang-II whose effects are blocked by the angiotensin receptor blocker, valsartan (reducing vasoconstriction and aldosterone release). (2) Sacubitril-valsartan has been used selectively in patients undergoing coronary artery bypass grafting (CABG) and ischemic cardiomyopathy due to safety concerns. In a prospective observational study done by Narayan and his colleagues in Patients with Ischemic Cardiomyopathy Undergoing Off-Pump Coronary Artery Bypass Grafting Primary outcome was tolerability and safety profile. Thirty consecutive patients undergoing CABG with EF \<40% were included. No mortality or readmissions occurred during 6 months' follow-up. One patient only experienced hypotension requiring discontinuation. Mild elevation in blood urea nitrogen, so Sacubitril-valsartan is well tolerated in patients with reduced EF undergoing CABG and proved its safety and efficacy. (3) Dapagliflozin is a highly potent, reversible and selective sodium-glucose cotransporter-2 inhibitor indicated worldwide for the treatment of type 2 diabetes. In numerous well-designed clinical studies dapagliflozin as monotherapy and combination therapy with other antihyperglycemic agents provided effective glycemic control and reduced bodyweight and blood pressure (BP) across a broad spectrum of patients. Dapagliflozin reduced the rate of cardiovascular (CV) death or hospitalization for heart failure (HF), did not adversely affect major adverse cardiovascular events (MACE) and possibly reduced progression of renal disease in patients with established atherosclerotic CV disease (CVD) or multiple risk factors for CVD. (4)
Maintaining stability of the genome requires dedicated DNA repair and signalling processes that are essential for the faithful duplication and propagation of chromosomes. These DNA damage response (DDR) mechanisms counteract the potentially mutagenic impact of daily genotoxic stresses from both exogenous and endogenous sources. Inherent to these DNA repair pathways is the activity of protein factors that instigate repair processes in response to DNA lesions. The regulation, coordination, and orchestration of these DDR factors is carried out, in a large part, by post-translational modifications, such as phosphorylation, ubiquitylation, and modification with ubiquitin-like proteins (UBLs). The importance of ubiquitylation and UBLylation with SUMO in DNA repair is well established, with the modified targets and downstream signalling consequences relatively well characterised. However, the role of dedicated erasers for ubiquitin and UBLs, known as deubiquitylases (DUBs) and ubiquitin-like proteases (ULPs) respectively, in genome stability is less well established, particularly for emerging UBLs such as ISG15 and UFM1. In this review, we provide an overview of the known regulatory roles and mechanisms of DUBs and ULPs involved in genome stability pathways. Expanding our understanding of the molecular agents and mechanisms underlying the removal of ubiquitin and UBL modifications will be fundamental for progressing our knowledge of the DDR and likely provide new therapeutic avenues for relevant human diseases, such as cancer.
FIELD: medicinal industry, pharmacy. SUBSTANCE: invention relates to production of drugs comprising nitroglycerol and used for acute stenocardia attacks arresting. In the process of preparing antianginal medicinal agent inert pharmaceutical filling agent is wetted with nitroglycerol solution in polar organic solvent and then with binding agent solution, dried, subjected for dry granulation and tableted in rotor tablet-press. Components are taken in the following ratio, wt.-%: nitroglycerol, 0.5-1.2; inert pharmaceutical filling agent, 92.8-98.8; binding agent, 0.5-5.0; stearic acid and/or calcium or magnesium stearates, 0.2-1.0. Tablet mass is 0.04-0.09 g. Decomposition index of nitroglycerol tablets is less 60 s, they are stable at storage in opened packages. Tablet quality satisfies to requirements of Pharmacopoeia and pharmacopoeia article "Tablets Nitrocardine sublingual". EFFECT: improved method of preparing, valuable properties of tablets. 7 cl, 10 tbl
People are advised to engage in weight-bearing physical activity to help prevent the loss of bone and muscle mass that occurs with aging. There is evidence from studies of animals that non-steroidal anti-inflammatory drugs (NSAIDS), such as ibuprofen, block some of the bone- and muscle-building effects of exercise. The aim of this study is to determine whether use of ibuprofen, either before or after exercise, blocks the benefits of exercise training on bone and skeletal muscle in older women and men. The hypothesis is that taking ibuprofen before exercise will block some of the effects of exercise training to increase bone density and muscle mass.

Women and men aged 60-75 years will complete a supervised, 9-month exercise training program designed to increase bone and muscle mass. The training will include weight lifting and weight-bearing exercises, such as jumping in place and treadmill walking, up to 5 days per week. Participants will be randomly assigned to take 1 of 3 study pill combinations before and after each exercise session. The combinations of study pills will be: placebo before/placebo after, placebo before/ibuprofen after, or ibuprofen before/placebo after. The dose of ibuprofen will be 400 mg. Bone density of the hip and spine, body composition (total body muscle and fat), and markers of bone turnover in the blood will be measured before and after 4.5 and 9 months of training. Muscle cross-sectional area of the thigh will be measured by CT before and after 9 months of training. A subset of participants will have biopsies of the thigh muscle before and after training to measure proteins and genes associated with muscle build-up and breakdown.

Volunteers who do not use ibuprofen, aspirin, or acetaminophen more than 3 days per month will be enrolled. People with intolerance to ibuprofen or related drugs, cardiovascular disease, or orthopedic problems that limit exercise will be excluded from the study.
BACKGROUND: Ocular ischemic syndrome (OIS) is a rare presentation of atherosclerotic carotid artery stenosis that can result in permanent visual loss. This severely disabling syndrome remains under diagnosed and undertreated due to lack of awareness; especially since it requires expedited multidisciplinary care. The relevance of early diagnosis and treatment is increasing due to an increasing prevalence of cerebrovascular disease.
METHODS: The long-term visual and cerebrovascular outcomes following intervention for nonarteritic OIS, remain poorly described and were the objective of this concise review. We conducted a PubMed search to include all English language publications (cohort studies and case reports) between 2002 and 2023.
RESULTS: A total of 33 studies (479 patients) report the outcomes of treatment of OIS with carotid endarterectomy (CEA, 304 patients, 19 studies), and carotid artery stenting (CAS, 175 patients, 14 studies). Visual outcomes were improved or did not worsen in 447 patients (93.3%). No periprocedural stroke was reported. Worsening visual symptoms were rare (35 patients, 7.3%); they occurred in the immediate postoperative period secondary to ocular hypoperfusion (3 patients) and in the late postoperative period due to progression of systemic atherosclerotic disease. Symptomatic recurrence due to recurrent stenosis after CEA was reported in 1 patient (0.21%); this was managed successfully with CAS. None of these studies report the results of transcarotid artery revascularization, the long-term operative outcome or stroke rate.
CONCLUSIONS: OIS remains to be an underdiagnosed condition. Early diagnosis and prompt treatment are crucial in reversal or stabilization of OIS symptoms. An expedited multidisciplinary approach between vascular surgery and ophthalmology services is necessary to facilitate timely treatment and optimize outcome. If diagnosed early, both CEA and CAS have been associated with visual improvement and prevention of progressive visual loss.
The supervised progressive endurance and resistance exercise program will be undertaken twice weekly in small groups and will be guided by an exercise physiotherapist over 12 weeks. All sessions will start with a warm-up passing over to the endurance training part and finish with a cool-down and will take approximately 60 minutes. The moderate-to-high-intensity endurance training will be performed at the beginning of each training session on a cycle ergometer for 20 min at 75 to 80 % of peak heart rate obtained from the baseline cardiorespiratory exercise test. This training intensity is within the range of intensities recommended by the American College of Sports Medicine (ACSM) exercise guidelines for cancer survivors. The moderate-to-high-intensity progressive resistance training regime (12 repetition maxima - 3 sets for each exercise) will include 6 exercises that target major upper and lower body muscle groups.
A substantial proportion of individuals addicted to heroin are incarcerated while addicted and a majority of individuals released from a correctional setting have a history of heroin addiction. The period immediately after release from incarceration is a particularly high-risk time for HIV transmission and other problems, including drug relapse and overdose. Methadone treatment is the most widely used opiate replacement therapy in the United States and has been shown to decrease HIV risk, as well as drug use, addiction relapse, and criminal activity. The purpose of this study was to evaluate the effectiveness of initiating opiate replacement therapy prior to release from incarceration on reducing HIV risk behaviors and drug relapse. In addition, this study evaluated the effectiveness of short-term payment versus non-payment of community opiate replacement therapy immediately following release from incarceration.

Participants in this were randomly assigned to 1 of 3 treatment groups. Participants enrolled in Group 1 initiated methadone opiate replacement therapy about 1 month prior to release from incarceration. They proceeded with a methadone program of their choice upon release and received short-term payment to cover treatment costs. Participants enrolled in Group 2 were referred to a methadone program of their choice and received short-term payment to cover treatment costs. Participants enrolled in Group 3 were referred to a program of choice upon release from incarceration without receiving financial assistance. All participants had the opportunity to partake in existing support programs available at the Rhode Island Department of Corrections while incarcerated and in the community upon release. Follow-up assessments occurred at Months 1.5, 6, and 12. These included interviews and urine specimens for toxicology analysis to verify self-reports.
The Hip Exercise (HE) program runs for 12 weeks, with exercise sessions 3 times per week. Each training session is scheduled to last approximately 30 minutes. The exercise program is home based with monthly supervision visits at the clinic.
The use of pursed lip breathing (PLB) to improve exercise tolerance in COPD patients has been widely documented. However, its efficacy in patients with interstitial lung disease (ILD) has yet to be confirmed. This study aims to determine if PLB improves perceived exertion and exercise capacity during a six-minute walk test (6MWT) in patients with ILD. To achieve this, a prospective randomized crossover trial will be performed, in which patients with ILD and restrictive ventilatory defect will be recruited via the ILD clinic of Hôpital Notre-Dame. The study will be performed in a single visit, on the day where patients attend a routine physician-prescribed follow-up 6MWT. Patients will be asked to perform a total of two 6MWT. Patients will be randomized to perform the first test with or without using PLB, and the order will be reversed for the second test, with patients serving as their own control. During tests, ventilatory variables will be continuously measured using a portable metabolic cart. The observed parameters will be: perceived exertion using the Modified-Borg Scale, respiratory rate, minute-ventilation, heart rate, peripheral oxygen saturation, and 6-minute walk distance (6MWD). It is expected that the use of PLB will be associated with a decrease of at least one unit on the Modified Borg Scale, which would be clinically significant. Moreover, it is expected that the decrease in dyspnea with PLB will be related to a decrease in respiratory rate minute ventilation during 6MWT. The clinical impact of this study could be significant as therapies allowing the improvement of dyspnea in patients with ILD are scarce.
A health information output device (10) is capable of using a health information storage unit (20) and a relative information storage unit (30) and comprises an acquisition unit (110), an identification unit (120), and an output unit (130). The health information storage unit (20) associates and stores, separately for each of a plurality of individuals, health information which pertains to the individual and individual identification information which is for identifying the individual. The relative information storage unit (30) stores relative information. The relative information makes it possible to identify, separately for each of the individuals, individual identification information of relatives of the individual. The acquisition unit (110) acquires the individual identification information of a subject. The identification unit (120) uses the relative information storage unit (30) to identify the individual identification information of relatives of the subject. The output unit (130) acquires, from the health information storage unit (20), health information which corresponds to the individual identification information that has been identified by the identification unit (120), and outputs the health information.
Compositions providing a stabilized antimicrobial formulation concentrate are described. The composition can include at least one glycol. The at least one glycol can include a first glycol with a carbon chain with less than six carbons. In some variations, the composition can include a non-ionic surfactant. The composition can also include hydroxyacetophenone. The hydroxyacetophenone can provide at least 10% of the composition by weight.
Quinidine is an antimalarial schizonticide and an antiarrhythmic agent with class 1A activity; it is the d-isomer of quinine, and its molecular weight is 324.43. Quinidine sulfate is the sulfate salt of quinidine; its chemical name is cinchonan-9-ol,6’- methoxy-,(9S)-, sulfate(2:1) dihydrate; its structural formula is:

Its molecular formula is: C40H48N4O4•H2SO4•2H2O; and its molecular weight is 782.96, of which 82.9% is quinidine base.

Quinidine sulfate occurs as fine needle-like, white crystals, frequently cohering in masses, or fine, white powder. It is odorless, has a very bitter taste, and darkens on exposure to light. It is slightly soluble in water, soluble in alcohol and in chloroform, and insoluble in ether.

Each tablet, for oral administration, contains 200 mg of quinidine sulfate (equivalent to 166 mg of quinidine base) 300 mg of quinidine sulfate (equivalent to 249 mg of quinidine base). In addition, each tablet contains the following inactive ingredients: confectioner’s sugar, corn starch, microcrystalline cellulose, pregelatinized starch and zinc stearate.
Mammary gland tumours are the most common neoplasms in intact bitches. Over the last decades, veterinary oncology has evolved in detecting and determining the lymph nodes to be removed in these patients for an accurate staging and prognosis, as well as to achieve better disease control and higher overall survival time. Our objective was to describe recent advances related to lymphatic drainage in bitches with mammary gland tumours, focusing on surgery, diagnosis, and prognosis. Through a systematic review using PubMed as the database, a thorough multi-step search reduced 316 studies to 30 for analysis. Vital dyes appear to be crucial in reducing the overall surgery time through transoperative staining of the lymph nodes. Imaging contrasts provide information regarding specific tumour drainage; however, there is still little evidence for their use. The axillary and superficial inguinal lymph nodes are well-established as regional lymph nodes of the cranial and caudal mammary glands. In sequence, accessory axillary, medial iliac, popliteal, and sternal lymph nodes should receive attention if they demonstrate contrast drainage, even considering that the literature has not shown a relationship between drainage and metastasis in these cases. In conclusion, recent studies have provided us with more support in regional lymph node excision regarding the TNM staging system. Studies are highly heterogeneous and method comparisons do not fit due to the non-uniformity of samples, materials, and procedures. We suggest further studies with a larger sample size, complete follow-up of patients, contrast use, and lymph node morphological and immunohistochemical analysis.
The recommended adult oral dosage for short-term treatment of active benign gastric ulcer is 800 mg h.s., or 300 mg four times a day with meals and at bedtime. Controlled clinical studies were limited to six weeks of treatment (see CLINICAL TRIALS). 800 mg h.s. is the preferred regimen for most patients based upon convenience and reduced potential for drug interactions. Symptomatic response to cimetidine does not preclude the presence of a gastric malignancy. It is important to follow gastric ulcer patients to assure rapid progress to complete healing.
Disclosed is a polynuclear molecular compound. The polynuclear molecular compound is prepared by synthesizing berberrubine and magnolol. The present invention provides an all-new polynuclear molecular compound for the first time. The polynuclear molecular compound is prepared by synthesizing berberrubine and magnolol, and medicament metabolism loops of absorption, distribution, metabolism and excretion of a single component or a mixture of two components are changed. Compared with berberrubine and magnolol, the toxicity of the obtained polynuclear molecular compound is one tenth of that of berberrubine and magnolol, so that the toxicity of the polynuclear molecular compound is remarkably reduced, the absorption rate is remarkably increased, the bioavailability is increased, the metabolism time is increased, a long-acting effect can be achieved, and the blood sugar reduction effect is improved. In addition, also disclose are a method for preparing the polynuclear molecular compound, and uses thereof in preparation of diabetes drugs.