anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Functional blockade of the transforming growth factor-beta (TGFβ) signalling pathway improves the efficacy of cytotoxic and immunotherapies. Here, we conducted a phase 1b study (ClinicalTrials.gov., NCT03143985) to determine the primary endpoints of safety, tolerability, and maximal tolerated dose (200 mg twice daily) for the orally-available TGFβ type I receptor kinase inhibitor vactosertib in combination with pomalidomide in relapsed and/or refractory multiple myeloma (RRMM) patients who had received ≥2 lines of chemoimmunotherapy. Secondary endpoints demonstrated sustained clinical responses, favorable pharmacokinetic parameters and a 6-month progression-free survival of 82%. Vactosertib combined with pomalidomide was well-tolerated at all dose levels and displayed a manageable adverse event profile. Exploratory analysis indicated that vactosertib co-treatment with pomalidomide also reduced TGFβ levels in patient bone marrow as well as the level of CD8+ T-cells that expressed the immunoinhibitory marker PD-1. In vitro experiments indicated that vactosertib+pomalidomide co-treatment decreased the viability of MM cell lines and patient tumor cells, and increased CD8+ T-cell cytotoxic activity. Vactosertib is a safe therapeutic that demonstrates tumor-intrinsic activity and can overcome immunosuppressive challenges within the tumor microenvironment to reinvigorate T-cell fitness. Vactosertib offers promise to improve immunotherapeutic responses in heavily-pretreated MM patients refractory to conventional agents.
Participants brushed for one timed minute with 1.6g of NaF/silica and 0.4 percent carbopol toothpaste containing 1450ppmF as NaF. Participants then swished the slurry around their mouth for 10 seconds, expectorated, then rinsed with water for 10 seconds.
Tesamorelin is a human growth hormone-releasing factor (GRF) analog produced synthetically. It is comprised of the 44 amino acid sequence of human GRF and a hexenoyl moiety, a C6 chain with a double bond at position 3, attached to the tyrosine residue at the N-terminal part of the molecule. Tesamorelin is prepared as an acetate salt. The molecular formula of tesamorelin acetate is C221H366N72O67S • x C2H4O2 (x ≈ 7) and its molecular weight (as free base equivalent) is 5135.9 Da. The structural formula of tesamorelin acetate is:

EGRIFTA SV (tesamorelin) for injection is a sterile, white to off-white, preservative-free lyophilized powder for subcutaneous injection. Each single-dose vial of EGRIFTA SV contains tesamorelin 2 mg (equivalent to approximately 2.2 mg of tesamorelin acetate) and the following inactive ingredients: 0.78 mg histidine, USP, 20 mg mannitol, USP, 0.05 mg polysorbate 20, NF and 10 mg sucrose, NF. Hydrochloric acid may be used to adjust the pH. The pH of EGRIFTA SV is between 4.5 and 7.4. After reconstitution with 0.5 mL of Sterile Water for Injection, resultant concentration is 2 mg/0.5 mL and the solution is clear and colorless.
With an aging population and growing indications for both MRI and CIEDs, it is estimated that patients with a CIED will have up to a 75% likelihood to meet some indication for MRI during their lifetime. MRI in patients with CIEDs has been increasingly shown to be a viable option in a variety of clinical circumstances under strict protocols and close monitoring. It is uncertain if MRI results in myocardial injury. Injury could occur due to heating of the lead(s) with myocardial heating and injury occurring at the lead tip.

A previous Mayo study published in 2016 showed no significant changes in cardiac troponin levels in the majority of patients with a CIED when MRI was performed. This study however was done using the older, less sensitive troponin assay. Unpublished data from the Mayo ED showed an increase in diagnosis of acute myocardial injury from 39% to 62% after implementation of the new hs-cTnT assay, reflecting its increased sensitivity. The previous Mayo study was also a retrospective study, and thus the data gathered was not as rigorously controlled as might be ideal.
Colorectal Cancer Awareness, Research, Education and Screening (CARES). At Baseline Visit, Participants in the CARES intervention will receive: I-FOBT kit, a newly developed DVD and booklet, and a mailed reminder card at two weeks post-intervention to remind them about FOBT testing, and follow-up assessments at 12 months.
Mirena consists of a T-shaped polyethylene frame (T-body) with a steroid reservoir (hormone elastomer core) around the vertical stem. The white T-body has a loop at one end of the vertical stem and two horizontal arms at the other end. The reservoir consists of a white or almost white cylinder, made of a mixture of LNG and silicone (polydimethylsiloxane), containing a total of 52 mg LNG. The reservoir is covered by a semi-opaque silicone membrane, composed of polydimethylsiloxane and colloidal silica. The T-body is 32 mm in both the horizontal and vertical directions. The polyethylene of the T-body is compounded with barium sulfate, which makes it radiopaque. A monofilament brown polyethylene removal thread is attached to a loop at the end of the vertical stem of the T-body. The polyethylene of the removal thread contains iron oxide as a colorant (see Figure 10).

The components of Mirena, including its packaging, are not manufactured using natural rubber latex.

Figure 10: Mirena
Irinotecan is a camptothecin analog which exerts its cytotoxic effects by forming a covalent complex with topoisomerase I and DNA, resulting in inhibition of DNA re-ligation, accumulation of DNA double strand breaks and apoptotic cell death (1). Irinotecan is FDA approved for use in the front-line and second-line treatment of colorectal cancer. It has also demonstrated activity in a variety of other non-hematologic tumors. The recently updated ASCO antiemetic guidelines characterize irinotecan as having moderate emetic risk. (2). However, the emetogenic potential of this agent has been poorly characterized and there are no published prospective trials with emesis as a primary-end point. In addition there is a complete paucity of information on the potential of irinotecan to induce emesis beyond the first day after chemotherapy, so-called delayed emesis. Best characterized following cisplatin, delayed emesis is also associated with a number of other chemotherapy agents that similar to irinotecan appear to be moderately emetogenic such as carboplatin, cyclophosphamide and doxorubicin. Antiemetic prophylaxis for delayed emesis following irinotecan is not routinely prescribed at the present time. Prospectively obtained information on the potential of irinotecan to cause delayed emesis would be helpful in guiding appropriate antiemetic practice.
Because of the dose ratio of dipyridamole to aspirin, overdosage of aspirin and extended-release dipyridamole is likely to be dominated by signs and symptoms of dipyridamole overdose. In case of real or suspected overdose, seek medical attention or contact a Poison Control Center immediately. Careful medical management is essential.

Based upon the known hemodynamic effects of dipyridamole, symptoms such as warm feeling, flushes, sweating, restlessness, feeling of weakness, and dizziness may occur. A drop in blood pressure and tachycardia might also be observed.

Salicylate toxicity may result from acute ingestion (overdose) or chronic intoxication. Severity of aspirin intoxication is determined by measuring the blood salicylate level. The early signs of salicylic overdose (salicylism), including tinnitus (ringing in the ears), occur at plasma concentrations approaching 200 mcg/mL. In severe cases, hyperthermia and hypovolemia are the major immediate threats to life. Plasma concentrations of aspirin above 300 mcg/mL are clearly toxic. Severe toxic effects are associated with levels above 400 mcg/mL. A single lethal dose of aspirin in adults is not known with certainty but death may be expected at 30 g.

Treatment of overdose consists primarily of supporting vital functions, increasing drug elimination, and correcting acid-base disturbances. Consider gastric emptying and/or lavage as soon as possible after ingestion, even if the patient has vomited spontaneously. After lavage and/or emesis, administration of activated charcoal as a slurry may be beneficial if less than 3 hours have passed since ingestion. Charcoal absorption should not be employed prior to emesis and lavage. Follow acid-base status closely with serial blood gas and serum pH measurements. Maintain fluid and electrolyte balance. Administer replacement fluid intravenously and augment with correction of acidosis. Treatment may require the use of a vasopressor. Infusion of glucose may be required to control hypoglycemia.

Administration of xanthine derivatives (e.g., aminophylline) may reverse the vasodilatory effects of dipyridamole overdose. Plasma electrolytes and pH should be monitored serially to promote alkaline diuresis of salicylate if renal function is normal. In patients with renal insufficiency or in cases of life-threatening intoxication, dialysis is usually required to treat salicylic overdose; however, since dipyridamole is highly protein bound, dialysis is not likely to remove dipyridamole. Exchange transfusion may be indicated in infants and young children.
The control of the urinary pH will be carried out twice a day: with the first urine in the morning and in the evening-night (approximately every 12h and at the same time). Measurements will be performed using the reactive strips.
Introduction: Epiploic appendagitis (EA) is an essential cause of abdominal pain that can be confused with more typical causes such as acute diverticulitis and appendicitis. Epiploic appendagitis accounts for 1% of all cases of abdominal pain in adults. The scarcity of information has limited its recognition as an essential nonsurgical cause of acute abdominal pain.Methods: We performed a systematic review of all EA cases published. We searched Scopus, Medline, Web of Science, and Google Scholar to retrieve all available studies from January 2000 to November 2023.Results: 196 case reports and case series were analyzed, with 371 patients with EA included. The mean age at the time of diagnosis was 39 years. Most patients were male (59%). The primary presenting symptoms were pain (100%), tenderness (59.5%), and rebound tenderness (27.4%). The left abdomen was the most common localization of pain (53%). The most frequently identified differential diagnoses were acute appendicitis (26.4%) and acute diverticulitis (16.1%). Most patients (53%) were treated conservatively, and 98 (26.4%) underwent surgical treatment. A significant difference in the choice of treatment was found for signs and symptoms such as rebound tenderness, nausea, anorexia, and diarrhea.Conclusions: Acute EA is an essential clinical condition of rare occurrence that might present a diagnostic challenge, as it can masquerade as another acute abdominal pain etiology. The optimal management of EA is conservative, so a higher recognition by surgeons and emergency physicians is essential to avoid unnecessary surgical interventions and their associated consequences.
NEW MATERIAL:A benzothiazole derivative shown by the formula I (R1 is H, lower alkyl, aryl, aralkyl, benzoyl, CF3, or halogen; R2 is lower alkyl) and its salt. EXAMPLE:7-[2-Hydroxy-3-(isopropylamino)propoxy]benzothiazole. USE:A drug. Having beta2-blocking action, yet having no or slightly relaxation inhibitory action on bronchus, showing relaxation action in contrast with this, having high action on cardiac muscle, exhibiting sufficient effect with its small amount, having small possibility of side effect. PREPARATION:A 2,3-epoxybenzothiazole derivative shown by the formula II is reacted with a lower alkylamine shown by the formula R2NH2 in an organic solvent such as methanol, etc. at room temperature -60 deg.C, to give a compound shown by the formula I .
SGLT2 inhibitors have been shown to provide pronounced reductions in cardiorenal outcomes, including cardiovascular death, heart failure, and renal failure. The mechanisms underlying these benefits remain uncertain. We hypothesized that the effects could be attributed to the elevated glycosuria induced by these drugs. Urine concentrations of glucose, creatinine, and ketones were measured at baseline and after 1 year of treatment with either placebo or canagliflozin 100 mg/day, in approximately 2,600 individuals from the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial (enrolling patients with type 2 diabetes, chronic kidney disease (CKD), and albuminuria). Associations between glycosuria and the primary composite end point from CREDENCE, and secondary outcomes were assessed using Cox proportional hazards models. Canagliflozin treatment increased fractional urinary glucose excretion (± SD) from 3 ± 9% at baseline to 30 ± 26% at year 1 (vs. 5 ± 19% with placebo; P < 0.001). Patients in the canagliflozin arm and in the top quartile of urine glucose to creatinine ratio at year 1 were significantly protected for the primary end point (hazard ratio [HR] 0.42; 95% CI 0.30-0.61); similar results were seen for cases of hospitalized heart failure (HR 0.45; 95% CI 0.27-0.73) and all-cause death (HR 0.56; 95% CI 0.39-0.80). These associations persisted when adjustments were made for multiple conventional risk factors. Among patients with type 2 diabetes and CKD treated with canagliflozin, individuals with the highest glycosuria levels had the strongest protection against multiple cardiorenal outcomes.
This study aimed to explore the expression of homeobox-containing 1 (HMBOX1) and its clinical significance in lung squamous cell carcinoma (LSCC). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of HMBOX1 in LSCC tissues. The relationship between HMBOX1 expression and clinical pathological data was analyzed by Chi-square or Fisher's exact test. Furthermore, the role of HMBOX1 in LSCC in vitro was detected by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide), flow cytometry and Western blot (WB) assays. HMBOX1 was highly expressed in LSCC tissues when compared with para-cancer tissues (P<0.05). According to the median expression of HMBOX1, the patients were divided into two groups, including high-expression group and low-expression group. HMBOX1 expression was correlated with tumor size, differentiation and clinical stage (P<0.05). Subsequent experiments indicated that LSCC cells with low expression of HMBOX1 exhibited significantly inhibited proliferation, G0/G1 block and promoted apoptosis (P<0.05). HMBOX1 expression was positively correlated with the expression of VEGF, elaborating that HMBOX1 probably promoted the growth of LSCC cells by affecting VEGF. HMBOX1 might contribute to the development of LSCC.
FIELD: biotechnology. SUBSTANCE: strain Erysipelothrix insioliosa ВГНКИ 6/24 showing high immunogenic activity and stability is proposed for preparing biopreparations against erysipelas in pigs. Strain ВГНКИ-6 is obtained by cloning of the parental strain on elective nutrient media and deposited in Collection of Microorganism ВГНКИ vetpreparations at number 24. Optimal strain growth on the nutrient media without addition of 5-10% native serum blood and 3-day broth culture of strain BP-2 inactivated by heating at 60 C is attained. Period of culture maturity after sowing on the nutrient media is 48 hr. Strain shows stable properties, high immunogenic activity for pigs but does not show immunogenicity for white mice. EFFECT: bacterial strain indicated above. 4 tbl
FIELD: medicine, oncology, medicinal microbiology. SUBSTANCE: bacterial mass of culture BCG-1 is filtered and diluted with stabilizing agent for two stages. After the first dilution up to concentration 50-60 mg of BCG in 1 ml the obtained suspension is centrifuged at separation factor 250 for 5 min and then the second dilution is carried out up to concentration 25 or 30 mg of BCG in 1 ml. Vaccine is poured into ampoules in the dose 1 ml and lyophilized. Invention provides to obtain standard curative vaccine with concentration 25 or 30 mg of BCG in 1 ml. EFFECT: enhanced indices of viability, homogeneity, dispersity and solubility. 2 tbl, 3 ex _
Alterations in autophagy have been observed in epilepsy, although their exact etiopathogenesis remains elusive. Transient Receptor Potential Mucolipin Protein 1 (TRPML1) is an ion channel protein that regulates autophagy and lysosome biogenesis. To explore the role of TRPML1 in seizures-induced neuronal injury and the potential mechanisms involved, an hyperexcitable neuronal model induced by Mg2+-free solution was used for the study. Our results revealed that TRPML1 expression was upregulated after seizures, which was accompanied by intracellular ROS accumulation, mitochondrial damage, and neuronal apoptosis. Activation of TRPML1 by ML-SA1 diminished intracellular ROS, restored mitochondrial function, and subsequently alleviated neuronal apoptosis. Conversely, inhibition of TRPML1 had the opposite effect. Further examination revealed that the accumulation of ROS and damaged mitochondria was associated with interrupted mitophagy flux and enlarged defective lysosomes, which were attenuated by TRPML1 activation. Mechanistically, TRPML1 activation allows more Ca2+ to permeate from the lysosome into the cytoplasm, resulting in the dephosphorylation of TFEB and its nuclear translocation. This process further enhances autophagy initiation and lysosomal biogenesis. Additionally, the expression of TRPML1 is positively regulated by WTAP-mediated m6A modification. Our findings highlighted crucial roles of TRPML1 and autophagy in seizures-induced neuronal injury, which provides a new target for epilepsy treatment.
The invention discloses a nano particle, a preparation method, application and a medicament thereof, and relates to the technical field of nano particles. The nano-particles comprise a gold nanorod inner core and a silver shell layer coated on the outer surface of the gold nanorod, the aspect ratio of the gold nanorod is 4-8, and the gold nanorod can be further prepared into an Au/Ag/Au nanorod or an Au/Ag/Au nanostar. The LSPR maximum absorption peak wavelength of the nano-particles falls in a near-infrared region II, the photothermal conversion efficiency is higher than that of the infrared region I, the photothermal treatment effect is good, and the bacterial cell ablation is facilitated. Photoacoustic imaging has higher tissue penetration depth, high temporal and spatial resolution. Ag released from external Ag shell + The antibacterial effect of the Au-containing antibacterial agent and the photo-thermal sterilization effect of the Au inside are cooperated, and the sterilization efficiency is higher. The nano-particles can be used for photoacoustic imaging and bacterial infection diagnosis and treatment agents, and can monitor Ag in a non-invasive manner + Topical delivery and photothermal treatment processes.
BACKGROUND: Neuroblastoma (NB) represents the most frequent and aggressive form of extracranial solid tumor of infants. Although the overall survival of patients with NB has improved in the last years, more than 50% of high-risk patients still undergo a relapse. Thus, in the era of precision/personalized medicine, the need for high-risk NB patient-specific therapies is urgent.
METHODS: Within the PeRsonalizEd Medicine (PREME) program, patient-derived NB tumors and bone marrow (BM)-infiltrating NB cells, derived from either iliac crests or tumor bone lesions, underwent to histological and to flow cytometry immunophenotyping, respectively. BM samples containing a NB cells infiltration from 1 to 50 percent, underwent to a subsequent NB cells enrichment using immune-magnetic manipulation. Then, NB samples were used for the identification of actionable targets and for the generation of 3D/tumor-spheres and Patient-Derived Xenografts (PDX) and Cell PDX (CPDX) preclinical models.
RESULTS: Eighty-four percent of NB-patients showed potentially therapeutically targetable somatic alterations (including point mutations, copy number variations and mRNA over-expression). Sixty-six percent of samples showed alterations, graded as "very high priority", that are validated to be directly targetable by an approved drug or an investigational agent. A molecular targeted therapy was applied for four patients, while a genetic counseling was suggested to two patients having one pathogenic germline variant in known cancer predisposition genes. Out of eleven samples implanted in mice, five gave rise to (C)PDX, all preserved in a local PDX Bio-bank. Interestingly, comparing all molecular alterations and histological and immunophenotypic features among the original patient's tumors and PDX/CPDX up to second generation, a high grade of similarity was observed. Notably, also 3D models conserved immunophenotypic features and molecular alterations of the original tumors.
CONCLUSIONS: PREME confirms the possibility of identifying targetable genomic alterations in NB, indeed, a molecular targeted therapy was applied to four NB patients. PREME paves the way to the creation of clinically relevant repositories of faithful patient-derived (C)PDX and 3D models, on which testing precision, NB standard-of-care and experimental medicines.
PURPOSE: Surgery for cochlear implantation is becoming increasingly common. It is a precise surgery and carries with it a number of very specific complications. Although uncommon, they can profoundly affect the recipients' quality of life. We report on our patients' population and compare with different series.
METHODS: This is a retrospective analysis of patients who underwent cochlear implant surgery in our center or who were referred for management of complications between November 2012 and November 2022.
RESULTS: There were 2126 patients aged 9 months-68 years [mean 3.2 yrs] with 147 adults > 18 yrs. The male: female ratio was nearly 1. We are reporting on late complications excluding device failures. There were 186 complications [8.7%], 124 minor complications [66% of the complications, 5.8% of the total population; and 62 major complications [ 33% of the complications and 2.9% of the total]. The commonest minor complication was surgical site infection [16%] and the commonest major complication was flap necrosis and device extrusion [26%].
CONCLUSION: Complications in our series were comparable to other series from different locations. But there seems to be a difference in the frequency of each complication depending on many factors which must be addressed. Standardization of reporting should be also more homogenized.
PURPOSE:To obtain the titled freeze-dried preparation having excellent thermal stability and solubility, by cooling an aqueous solution of gabaxate mesylate having a specific concentration range quickly below a specific temperature to effect the freezing of the solution, raising the temperature and keeping at the level, cooling again, and drying in vacuum. CONSTITUTION:2-25w/v% aqueous solution of gabexate mesylate of formula is frozen by cooling quickly to <=-25 deg.C, preferably to -40 deg.C, and the frozen block is heated at -2--18 deg.C, preferably -7--10 deg.C, and maintained at the temperature for >=30min, preferably 2-3hr. Thereafter, the frozen block is cooled again at <=-25 deg.C and vacuum-dried under reduced pressure to obtain a crystalline freeze-dried preparation of gabexate mesylate. The preparation is useful as a dissolution-in-use injection for acute pancreatitis, chronic recurrent pancreatitis, etc. induced by the elimination of proteinase. It has high solubility, keeps excellent stability of the crystal of the compound, is free from shrinkage by moisture absorption, and gives an injection free from insoluble materials when dissolved in water in use.