anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
INLYTA as a Single Agent

In a controlled clinical study with INLYTA for the treatment of patients with RCC, alanine aminotransferase (ALT) elevations of all grades occurred in 22% of patients on both arms, with Grade 3/4 events in <1% of patients on the INLYTA arm. When used as a single agent, monitor ALT, aspartate aminotransferase (AST) and bilirubin before initiation of and periodically throughout treatment with INLYTA.

INLYTA in Combination with Avelumab or with Pembrolizumab

INLYTA in combination with avelumab or with pembrolizumab can cause hepatotoxicity with higher than expected frequencies of Grade 3 and 4 ALT and AST elevations. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt or permanently discontinue INLYTA and avelumab or pembrolizumab, and administer corticosteroids as needed [see Dosage and Administration (2.3)].

With the combination of INLYTA and avelumab, Grades 3 and 4 increased ALT and increased AST were reported in 9% and 7% of patients, respectively. In patients with ALT ≥3 times ULN (Grades 2–4, n=82), ALT resolved to Grades 0–1 in 92%. Among the 73 patients who were rechallenged with either avelumab (n=3) or axitinib (n=25) administered as a single agent or with both (n=45), recurrence of ALT ≥3 times ULN was observed in no patient receiving avelumab, 6 patients receiving INLYTA, and 15 patients receiving both avelumab and INLYTA. Twenty-two (88%) patients with a recurrence of ALT ≥3 ULN subsequently recovered to Grade 0–1 from the event. Immune-mediated hepatitis was reported in 7% of patients including 4.9% with Grade 3 or 4 immune-mediated hepatitis. Hepatotoxicity led to permanent discontinuation in 7% and immune-mediated hepatitis led to permanent discontinuation of either avelumab or INLYTA in 5% of patients. Thirty-four patients were treated with corticosteroids and one patient was treated with a non-steroidal immunosuppressant. Resolution of hepatitis occurred in 31 of the 35 patients at the time of data cut-off.

With the combination of INLYTA and pembrolizumab, Grades 3 and 4 increased ALT (20%) and increased AST (13%) were seen. Fifty-nine percent of the patients with increased ALT received systemic corticosteroids. In patients with ALT ≥3 times ULN (Grades 2–4, n=116), ALT resolved to Grades 0–1 in 94%. Among the 92 patients who were rechallenged with either pembrolizumab (n=3) or INLYTA (n=34) administered as a single agent or with both (n=55), recurrence of ALT ≥3 times ULN was observed in 1 patient receiving pembrolizumab, 16 patients receiving INLYTA, and 24 patients receiving both pembrolizumab and INLYTA. All patients with a recurrence of ALT ≥3 ULN subsequently recovered from the event.
An activator of the Rse and Mer receptor protein tyrosine kinases has been identified. The activator is encoded by growth arrest-specific gene 6 (gas6). Accordingly, the invention provides a method of activating the Rse or Mer receptor using gas6 polypeptide. Furthermore, the invention provides a method of enhancing survival, proliferation or differentiation of cells having the Rse or Mer receptor incorporated in their cell membranes which involves exposing those cells to gas6 polypeptide. The types of cells which can be treated according to the method include glial cells such as Schwann cells and mononuclear cells. Kits and articles of manufacture which include gas6 polypeptide are further provided. The invention also relates to gas6 variants.
After the tolerable cell dose (TCD) has been determined in adults, up to 18 additional subjects may be enrolled in an expansion cohort at the TCD. A TCD is defined as the dose at which approximately 0.20 of subjects experience dose limiting toxicity (0 - 1 out of 6 subjects).
Vitamin D deficiency is common around the world. In Finland vitamin D levels are low in all age groups. Especially infants are predisposed to vitamin D deficiency. Partly this is due to low exposure to sunlight but mainly it is due to low dietary intake of vitamin D. Vitamin D prophylaxis was introduced in Finland in the 1950´s to overcome rickets. However, the recommended dose has decreased from 50µg (2000 IU) in the 1960´s to 10µg (400 IU) from beginning of the 1990´s. The serum concentration of 25-hydroxyvitamin D (S-25OHD) is used as a marker of vitamin D status in the body. Although there is no consensus of optimal concentration of S-25OHD, it has been proposed that concentrations lower than 50 nmol/l indicate deficiency. According to recent findings on 25-OHD concentrations in Finnish children, currently recommended intake of vitamin D is inadequate.
Substitution of lost neurons by neurotransplantation would be a possible management of advanced degenerative cerebellar ataxias in which insufficient cerebellar reserve remains. In this study, we examined the volume and structure of solid embryonic cerebellar grafts in adult Lurcher mice, a model of olivocerebellar degeneration, and their healthy littermates. Grafts taken from enhanced green fluorescent protein (EGFP)-positive embryos were injected into the cerebellum of host mice. Two or six months later, the brains were examined histologically. The grafts were identified according to the EGFP fluorescence in frozen sections and their volumes were estimated using the Cavalieri principle. For gross histological evaluation, graft-containing slices were processed using Nissl and hematoxylin-eosin staining. Adjustment of the volume estimation approach suggested that it is reasonable to use all sections without sampling, but that calculation of values for up to 20% of lost section using linear interpolation does not constitute substantial error. Mean graft volume was smaller in Lurchers than in healthy mice when examined 6 months after the transplantation. We observed almost no signs of graft destruction. In some cases, compact grafts disorganized the structure of the host's cerebellar cortex. In Lurchers, the grafts had a limited contact with the host's cerebellum. Also, graft size was of greater variability in Lurchers than in healthy mice. The results are in compliance with our previous findings that Lurcher phenotype-associated factors have a negative effect on graft development. These factors can hypothetically include cerebellar morphology, local tissue milieu, or systemic factors such as immune system abnormalities.
PURPOSE:To provide the subject new compound having excellent antibacterial action, antitumor action and anti-AIDS virus action and extremely useful as an antibacterial agent, an antitumor agent and a therapeutic agent for AIDS. CONSTITUTION:The thiazetoquinoline-3-carboxylic acid derivative of formula I [R<1> is H or lower alkyl; R<2> is (substituted)cycloamino; X is H or halogen] or its salt, e.g. 1-methyl-4-oxo-7-[(S)-3-trifluoroacetylamino-1-pyrrolidinyl]-1H,4 H-[1,3]-thiazeto[3,2-a]quinoline-3-carboxylic acid ethyl ester. The objective compound is produced by reacting a 7-halogenothiazetoquinoline-3-carboxylic acid derivative of formula II (Y is halogen) with a (substituted)amine in a solvent such as methanol. The compound of formula II can be produced e.g. by reacting a compound of formula III with diethyl malonate, 3-fluorophenyl isothiocyanate and ClCH2OCH3 and converting the obtained compound of formula IV through a compound of formula V into the compound of formula II.
The control group will wear a Fitbit step counter for 8 weeks. In addition, participants will use the Go\&Grow fitness app without the social features for 6 weeks.
The present invention relates to high-efficiency mycin invented by the inventor through multiple tests, which is an antibiotic medicine integrating the functions of clearing heat, removing toxicity, diminishing inflammation, relieving pain, sterilizing, relieving cough, reducing sputum, improving eyesight, lowering blood pressure and resisting allergy into a whole. Compared with any new medicine at present, the present invention has the advantages of rapid effect taking, high curative effect and allergy resisting property in an aspect of diminishing the inflammation. Compared with the most advanced medicine, the present invention can be used for curing acute bronchitis and pneumonia for 6/10 days in advance. The antibiotic medicine can be used through external application, oral administration and intravenous injection, wherein oral mucosa tissue ulcers, malignant sores, eczema, infectious conjunctivitis and mosquito bites can be treated by the antibiotic medicine through the external application; disease symptoms of laryngitis, urethritis, pneumonia, acute bronchitis, phthisis, hyperpyrexia, chemical poisoning, skin allergy, thick sputum which is difficult to vomit, hypertension, etc. can be treated by the antibiotic medicine through the oral administration and the intravenous injection. The raw material cost for producing one kilogram of the antibiotic medicine (herbal piece prepared for decoction) is 10 yuan.
As a broad-spectrum anticancer drug, cisplatin is widely used in the treatment of tumors in various systems. Unfortunately, several serious side effects of cisplatin limit its clinical application, the most common of which are nephrotoxicity and ototoxicity. Studies have shown that cochlear hair cell degeneration is the main cause of cisplatin-induced hearing loss. However, the mechanism of cisplatin-induced hair cell death remains unclear. The present study aimed to explore the potential role of activating transcription factor 6 (ATF6), an endoplasmic reticulum (ER)-localized protein, on cisplatin-induced ototoxicity in vivo and in vitro. In this study, we observed that cisplatin exposure induced apoptosis of mouse auditory OC-1 cells, accompanied by a significant increase in the expression of ATF6 and C/EBP homologous protein (CHOP). In cell or cochlear culture models, treatment with an ATF6 agonist, an ER homeostasis regulator, significantly ameliorated cisplatin-induced cytotoxicity. Further, our in vivo experiments showed that subcutaneous injection of an ATF6 agonist almost completely prevented outer hair cell loss and significantly alleviated cisplatin-induced auditory brainstem response (ABR) threshold elevation in mice. Collectively, our results revealed the underlying mechanism by which activation of ATF6 significantly improved cisplatin-induced hair cell apoptosis, at least in part by inhibiting apoptosis signal-regulating kinase 1 expression, and demonstrated that pharmacological activation of ATF6-mediated unfolded protein response is a potential treatment for cisplatin-induced ototoxicity.
Anaplastic large cell lymphoma (ALCL) is a rare and aggressive peripheral T-cell lymphoma affects lymph nodes and extra-nodal sites with characteristic skin lesions. Approximatively half of the tumors express the NPM1-ALK fusion from the translocation t(2;5)(p23;q32). In the present study, the inventors identify ROR2 as progressively up regulated thought tumorigenesis. Patient samples show a significantly high ROR2 expression (transcriptomic data) as well as a strong ROR2 protein expression (IHC) with some tumors displaying a clear membrane signal. ROR2 mRNA expression level is also positively correlated to NPM-ALK expression level in tumor cells and is not expressed in normal T cells. In addition, ROR2 protein level is significantly increased in resistant cells to the ALK inhibitor, crizotinib, used in clinical trials for children with refractory tumors. This result opens the road to ROR2 specific therapies: ROR2 inhibitors, monoclonal antibodies therapies or even ROR2 specific CAR cells, including for ALCL ALK(+) resistant tumors.
Patients who are enrolled in the TNMT group will participate in 12 sessions of supervised outpatient physical therapy over a six week period. The TNMT protocol is distinguished by performance of exercises designed to enhance core and hip strength, performance of neuromuscular training exercise that are designed to correct movement flaws associated with second ACL injury25, providing verbal and visual feedback and performance of single leg drills on both legs.
All treatment will be provided via the Velibra website: https://velibra.broca.io/en/registration/voucher. While the Velibra treatment is only six weeks long, participants will have free access to the program for 24 weeks. They can access this website as often as they would like. The Velibra program is self-guided, so participants determine how often they access the material (the program encourages participants to complete one of six sessions per week for six weeks).
Participant with postoperative negative NephroCheck® (NC) (AKIRisk score was ≤ 0.3 nanogram per milliliter (ng/mL)\^2/1000 at all assessments between 2 to 22 hours after time point 0 (T0) were followed up for 90 days in observational cohort. Participants did not receive any intervention.
The purpose of this study is to clarify whether swallowing function can be inferred from grip strength. Based on the diagnostic criteria of sarcopenia, patients were divided into two groups according to grip strength, and it was analyzed whether there was a difference in the evaluation index for swallowing function between the two groups. Among the cases requesting evaluation of swallowing function from June 10, 2020 to October 28, 2020, 83 cases (mean age: 71.7 years, 59 males and 24 females) who received assessment tests and swallowing endoscopy were included. According to the diagnostic criteria for grip strength in the Asian working group in Sarcopenia, less than 28 kgf and 18 kgf were defined as the weak group for men and women, respectively. Hyodo scores, repeated salivary swallowing tests (RSST), maximum vocalization time (MPT), and dysphagia severity classification (DSS) were compared between the two groups. Of the 83 patients, 29 and 54 were in the normal group and weak group, respectively. In all indicators, the normal group showed significantly better results than the weak group: Hyodo score (2.4 vs. 4.0, p < 0.01), RSST (4.1 times vs. 2.4 times, p < 0.01), MPT (12.1 s vs. 5.9 s, p < 0.001), DSS (4.5 vs. 5.9, p < 0.001), respectively. In multiple regression analysis with DSS as the dependent variable, grip strength was a significant independent variable of DSS even after adjusting for age, gender, and body mass index. Grip strength assessment based on sarcopenia criteria can be a useful tool for estimating swallowing function.
In certain aspects, disclosed herein are novel compositions and methods related to either the enhancement or inhibition of erythropoiesis that are useful, for example, in the treatment of anemia or erythrocytosis. For example, disclosed is: - a method of stimulating erythropoiesis in a subject with anemia comprising administering to the subject an agent that binds to MS 1r; - a method of stimulating erythropoiesis in a subject with anemia comprising administering to the subject an agent that binds to IL-17ra; - a method of stimulating erythropoiesis in a subject with anemia comprising administering to the subject an agent that inhibits the binding of WNT5a to RYK. - a method of inhibiting erythropoiesis in a subject with erythrocytosis comprising administering to the subject an agent that binds to MST1r. - a method of inhibiting erythropoiesis in a subject with erythrocytosis comprising administering to the subject an agent that binds to RYK. - a method of inhibiting erythropoiesis in a subject with erythrocytosis comprising administering to the subject an agent that inhibits the binding of IL-17a to IL-17ra.1ts t - methods of determining whether a test agent is an inhibitor of erythropoiesis involving IL.17ra, MST1r or RYK-protein. - a method of expanding or propagating erythroid progenitor cells  in vitro  comprising culturing the erythroid progenitor cells with an agent that inhibits Ryk or Mst1r to a cell medium comprising the progenitor cells.
In animal studies with olanzapine, the principal hematologic findings were reversible peripheral cytopenias in individual dogs dosed at 10 mg/kg (17 times the maximum recommended human daily oral dose on a mg/m 2 basis), dose-related decreases in lymphocytes and neutrophils in mice, and lymphopenia in rats. A few dogs treated with 10 mg/kg developed reversible neutropenia and/or reversible hemolytic anemia between 1 and 10 months of treatment. Dose-related decreases in lymphocytes and neutrophils were seen in mice given doses of 10 mg/kg (equal to 2 times the maximum recommended human daily oral dose on a mg/m 2 basis) in studies of 3 months' duration. Nonspecific lymphopenia, consistent with decreased body weight gain, occurred in rats receiving 22.5 mg/kg (11 times the maximum recommended human daily oral dose on a mg/m 2 basis) for 3 months or 16 mg/kg (8 times the maximum recommended human daily oral dose on a mg/m 2 basis) for 6 or 12 months. No evidence of bone marrow cytotoxicity was found in any of the species examined. Bone marrows were normocellular or hypercellular, indicating that the reductions in circulating blood cells were probably due to peripheral (non-marrow) factors.
PURPOSE: To obtain a nonaqueous solution remarkably improved in high- temperature stability by including doxorubicin hydrochloride and a specific antioxidant in a solvent medium composed of propylene glycol, etc., and water and regulating the pH within a specified range. CONSTITUTION: This nonaqueous solution of doxorubicin hydrochloride is obtained by including 5-10mg/mL doxorubicin hydrochloride and 1-2mg/mL, preferably 0.5-2mg/mL antioxidant selected from α-tocopherol, sodium- formaldehyde bisulfite and tertiary butylhydroquinone and citric acid in an amount required to regulate the pH of the solution to 3-5, preferably 3-4.5 in a solvent medium composed of 90-100% (vol./vol.) propylene glycol, 1,2- dihydroxybutane or 1,3-dihydroxypropane and 0-10% (vol./vol.) water. When the water content in the solvent medium is about 5 10 (vol./vol.), the doxorubicin hydrochloride is used at about 5-20mg/mL concentration.
Patients aged 65 years or younger who can tolerate FCR： Patients in this group will receive zanubrutinib monotherapy for 12 months, then receive 4 cycles of zanubrutinib, fludarabine, cyclophosphamide and rituximab(ZFCR). Efficacy evaluation and MRD test of peripheral blood and bone marrow were performed at the 17th cycle after 16 cycles to obtain study end point data. Patients with CR/CRi and MRD negative could stop taking zanubrutinib, and other patients could stop taking zanubrutinib or continue treatment. Follow-up and efficacy assessment were conducted every three months.
The disclosure notably relates to a syringe. The syringe comprises a barrel forming a medicament reservoir therein. The medicament reservoir is capable of fluid communication with a needle hub at a distal end thereof. The syringe further comprises a stopper. The stopper seals the medicament reservoir. The stopper is slidable inside the barrel toward the distal end. The syringe further comprises a plunger assembly. The plunger assembly comprises a plunger rod and a spring. The spring is arranged between a distal end of the plunger rod and the stopper. The spring is configured to transmit to the stopper a forward axial movement of the plunger rod, thereby causing a forward axial movement of the stopper into the medicament reservoir in order to expel the medicament through the needle hub. The plunger rod is axially movable between a proximal extremal position and a distal extremal position. The spring is in a relaxed state when the plunger rod is at the proximal extremal position.
An increase in agent residence time at a tissue site is provided for by the presence of a barrier. The barrier is a separate entity from the agent when introduced to the tissue. A binding member is included in the barrier for coupling the barrier to the surface of the tissue. In one embodiment, agent is introduced to the tissue prior to attachment of the barrier to the tissue. In another embodiment, agent is presented after the barrier is positioned on the tissue surface. A delivery vehicle may be used to administer the agent and barrier to a patient.
Cachexia, which affects 50-80% of cancer patients, is a debilitating syndrome that leads to 20% of cancer-related deaths. A key feature of cachexia is adipose tissue atrophy, but how it contributes to the development of cachexia is poorly understood. Here, we demonstrate in mouse models of cancer cachexia that white adipose tissue browning, which can be a characteristic early-onset manifestation, occurs prior to the loss of body weight and skeletal muscle wasting. By analysing the proteins differentially expressed in extracellular vesicles derived from cachexia-inducing tumours, we identified a molecular chaperone, Glucose-regulated protein 75 (GRP75), as a critical mediator of adipocyte browning. Mechanistically, GRP75 binds adenine nucleotide translocase 2 (ANT2) to form a GRP75-ANT2 complex. Strikingly, stabilized ANT2 enhances its interaction with uncoupling protein 1, leading to elevated expression of the latter, which, in turn, promotes adipocyte browning. Treatment with withanone, a GRP75 inhibitor, can reverse this browning and alleviate cachectic phenotypes in vivo. Overall, our findings reveal a novel mechanism by which tumour-derived GRP75 regulates white adipose tissue browning during cachexia development and suggest a potential white adipose tissue-centred targeting approach for early cachexia intervention.
PURPOSE: To compare the outcomes of pars plana vitrectomy (PPV) and combined PPV with phacoemulsification (PPVCE) surgeries for proliferative diabetic retinopathy (PDR) and cataract treatment.
METHODS: Retrospective analysis of 120 diabetic patients who underwent PPV or PPVCE.
RESULTS: The key outcome indicators were best-corrected visual acuity (BCVA) and post-operative complications. The PPVCE group had an average age of 53 years, with 50% females and 50% males. The initial visual acuity (VA) was 1.84 log MAR. In this group, BCVA remained stable or increased in 61 eyes (74%). Regarding the PPV group, the average age was 43 years; 65% were men while 34% were women. The initial VA was 1.83 log MAR; in this group, the VA increased or remained stable in 28 eyes (73%). The evolution of the VA was rather symmetric in the two groups without a significant difference (P = 0.9). Similarly, the occurrence of postoperative complications was comparable for the main complications studied, namely the inflammatory reaction (P = 0.809), ocular hypertension (P = 0.344), corneal edema (P = 0.07), and neovascular glaucoma (P = 0.413). However, there was a decrease in BCVA (three lines) in the PPV group after 6 months of follow-up (P = 0.05) in patients with a clear lens preoperatively and who developed a clinically evident cataract.
CONCLUSION: According to this study, for diabetic patients with severe cataracts and vitreoretinal disease requiring vitrectomy, combining vitrectomy with phacoemulsification as a single surgical intervention may be a suitable therapeutic choice. This approach does not significantly increase the risk of visual impairment or retinopathy development.
Guideline-Directed Medication Treatment contains ACEI/ARB/ARNI, β blocker, SGLT2i and MRA. The patients in this group were tolerable to all the medications and accepted GDMT.