anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Tropomyosin receptor kinases (TRK) are attractive targets for cancer therapy. As TRK-inhibitors are approved for all solid cancers with detectable fusions involving the Neurotrophic tyrosine receptor kinase (NTRK)-genes, there has been an increased interest in optimizing testing regimes. In this project, we wanted to find the prevalence of NTRK fusions in a cohort of various histopathological types of early-stage lung cancer in Norway and to investigate the association between TRK protein expression and specific histopathological types, including their molecular and epidemiological characteristics. We used immunohistochemistry (IHC) as a screening tool for TRK expression, and next-generation sequencing (NGS) and fluorescence in situ hybridization (FISH) as confirmatory tests for underlying NTRK-fusion. Among 940 cases, 43 (4.6%) had positive TRK IHC, but in none of these could a NTRK fusion be confirmed by NGS or FISH. IHC-positive cases showed various staining intensities and patterns including cytoplasmatic or nuclear staining. IHC-positivity was more common in squamous cell carcinoma (LUSC) (10.3%) and adenoid cystic carcinoma (40.0%), where the majority showed heterogeneous staining intensity. In comparison, only 1.1% of the adenocarcinomas were positive. IHC-positivity was also more common in men, but this association could be explained by the dominance of LUSC in TRK IHC-positive cases. Protein expression was not associated with differences in time to relapse or overall survival. Our study indicates that NTRK fusion is rare in early-stage lung cancer. Due to the high level of false positive cases with IHC, Pan-TRK IHC is less suited as a screening tool for NTRK-fusions in LUSC and adenoid cystic carcinoma.
Pregnancy Exposure Registry– Use with ribavirin 

A ribavirin Pregnancy Registry has been established to monitor maternal and fetal outcomes of pregnancies of female patients and female partners of male patients exposed to ribavirin during pregnancy or who become pregnant within 6 months following cessation of treatment with ribavirin. Healthcare providers and patients are encouraged to report such cases by calling 1-800-593-2214.

Risk Summary

There are no adequate and well-controlled studies of PEGASYS in pregnant women to inform a drug-associated risk. Based on animal reproduction studies, PEGASYS can cause fetal harm and should be assumed to have abortifacient potential. Non-pegylated interferon alfa-2a treatment caused abortion when given to pregnant rhesus monkeys (see Data). The background risk of major birth defects and miscarriage in the indicated population is 3% and 4-22%, respectively. In the U.S. general population, the estimated background risk for major birth defects and miscarriage in the clinically recognized pregnancies is 2-4% and 15-20%, respectively. 

PEGASYS combination treatment with ribavirin is contraindicated in women who are pregnant and in the male partners of women who are pregnant [see Contraindications (4), Warnings and Precautions (5.1), and ribavirin labeling] . Significant teratogenic and/or embryocidal effects have been demonstrated in all animal species exposed to ribavirin [see ribavirin labeling].

Data

Animal Data –Groups of 8 or 9 pregnant rhesus monkeys were given non-pegylated interferon alfa-2a by daily intramuscular injection over days 22 to 70 of gestation at doses of 1, 5 and 25 million IU/day. Two, 3 and 6 monkeys aborted in the low, mid and high dose groups compared with 1 in the control group. Maternal toxicity, characterized by transient body weight loss, was seen at all dose levels. There were too few remaining pregnancies to assess teratogenic potential but no developmental abnormalities were observed in surviving fetuses.
Digital manipulation of thyroid cartilage (DMT) Duration: Each child was given 15-20 minute session. Frequency: Twice in a week. Total 24 sessions were performed. The aim of DMT was to reduce the severity of stuttering and improve the fluency.
PURPOSE: Provided is a composition for treating obesity and constipation which contains extracts of pine needle, green tea and black tea as an active ingredient. The increases obesity inhibition effect, reduces body weight and body fat, and increase quantity of feces. Therefore, it has excellent effects on prevention and treatment of obesity and constipation. CONSTITUTION: The pine needle, green tea and black tea are respectively extracted by using hot water of predetermined temperature. Each of the extracts are mixed in a mixing ratio of 1-4:1-4:1-4. The composition for prevention and treatment of obesity and constipation contains the mixed extracts as an active ingredient.
FIELD: veterinary science. SUBSTANCE: preparation has bactericidal and antiinflammatory agents (anilocaine) and the base (consistent emulsion). Composition has additionally dimexide to enhance bactericidal effect. Therapeutic effectiveness of the preparation is 64-100% and prophylaxis effectiveness is 80-85% depending on mastitis forms. Also, the preparation shows high effectiveness for wound healing, skin softening and edemas release. EFFECT: enhanced effectiveness of the preparation proposed.
OBJECTIVE: The aim of this descriptive study was to propose diagnostic criteria for acute exacerbation of trigeminal neuralgia (TN) based on the analysis of retrospective cases.
BACKGROUND: TN is a rare and extremely painful condition whose evolution can be punctuated by major exacerbations, leading to significant functional impairment. Several denominations are used for these exacerbations: "acute exacerbation", "status of trigeminal neuralgia", and "status trigeminus". There is currently no clinical definition of this state. In this manuscript, we used the term "status trigeminal neuralgia" (STN).
METHODS: We conducted a retrospective study, in a tertiary care specialist headache center, in France. Patients were selected from January 2015 to October 2022, with the French translation of the keyword "STN", in the medical records (outpatients) or the codage for trigeminal neuralgia (inpatients). Additional cases of STN were prospectively recruited from October 2022 to February 2023. We analyzed the clinical and paraclinical data of these patients.
RESULTS: Thirty-nine patients presenting with STN were included. There was a preponderance of women (64%) with 24 cases of classic TN (62%) and 15 cases of secondary TN (38%). Concerning STN, 39 episodes were described. Pain was very severe in all patients. Cranial autonomic signs were present in 23% of cases. Pain extended beyond the usual territory in 44% of cases. A continuous pain background was present in 35% of cases. With regard to triggering factors, paroxysms of facial pain were triggered by eating (97% of patients), speaking (90%) or drinking (62% of patients). Repercussions on weight, hydration, or mood disorders were observed in 67%, 56% and 59% of the cases, respectively.
CONCLUSION: STN is a rare clinical presentation of TN. We proposed criteria and a new denomination for this condition.
Surgical site infection (SSI) after spine surgery is a devastating complication. Spine SSIs occur in as many as 40,000 people each year, causing considerable disability and resulting in re-operative costs of over $100,000. Even with the use of standard perioperative infection prevention techniques, SSIs occur as often as 3-5% depending on the surveillance technique and time-window used, with widespread variability between practice sites and surgeons. A mainstay of SSI prevention is the timely administration of antibiotics, but one of the limits of intravenous antibiotic prophylaxis is that bone tissue concentrations of antibiotics are lower than blood levels. As a result, there has been increasing interest in the use of in-wound antibiotics (IWA), placed directly on the spine at the completion of surgery. IWAs have been supported by several observational studies with a recent systematic review suggesting an 84% decrease in SSI. However, most of these studies failed to address important confounding in the ways IWA were used and had variable follow-up. The only IWA randomized controlled trial (RCT), albeit underpowered failed to identify a protective effect, leading to uncertainty about the role of IWA. Because of the relative infrequency of SSI, variable windows of follow-up and high rates of confounding in prior studies of IWA a large scale trial of IWA with an appropriate follow-up period is needed to evaluate its effectiveness in spine surgery. Such a trial would be more feasible if randomization occurred at the level of hospital "cluster" (cRCT), to account for existing variation in practices regarding IWA use, variable rates of SSI, and use of other SSI prevention techniques.

Several pilot and feasibility questions need to be addressed before a cRCT of IWA can be proposed. SSI can appear as long as a year after spine surgery and short follow-up time in prior studies may have undercounted events and may have failed to recognize SSIs that may have been potentially delayed in detection because of the IWA. For example, the rationale for surgeon use of IWA, antibiotic type, or dose is unclear, as is whether surgeons use IWA in a similar fashion across patients and sites and if this represents confounding for which researchers must account. It is also unclear if surgeon use of IWAs is related to knowledge about existing data, beliefs and attitudes that may be barriers or enablers to a trial that promotes greater use of IWAs. To address these issues and direct an eventual cRCT, the investigators will perform surveys of spine surgeons assessing knowledge, behaviors and attitudes about IWA.
A device to determine the level of a substance of interest in a patient's body and provide a therapeutic amount of medicament is disclosed. The level of a substance of interest in the patient's body is determined by iontopheretically sampling the patient's blood and then analyzing the resulting sample to determine the level of the substance of interest. The information about the level of a substance of interest is transmitted to an implanted drug pump in the patient's body. In the preferred embodiment, the substance of interest sensor is an external sensor applied to the user's skin. In an alternate embodiment, the sensor may be implanted. The preferred method of transmitting information about the level of a substance of interest determined by the sensor is transmitted to an implanted drug pump in the patient's body is via a so called “body bus”. The “body bus” is a telemetry system where the patient's own body provides the interconnection between the iontopheretic device and the implanted drug pump.
Chronic limb-threatening ischemia (CLTI) significantly increases the risk of major adverse limb events (MALE) and major adverse cardiac events (MACE) after lower extremity revascularization (LER). This study aims to identify novel biomarkers that help to further reduce the risk of postoperative cardiovascular complications. In this prospective, nonrandomized, observational study, baseline serum levels of sirtuin 1 (SIRT1) were assessed in 147 diabetic patients scheduled for LER due to CLTI, and participants were followed for the occurrence of MALE and MACE over 12 months. Fifty-three patients experienced MALE, and 33 experienced MACE within the follow-up period. Lower baseline SIRT1 levels were significantly associated with an increased risk of MALE and MACE, independent of other risk factors. The ROC curve analysis identified a SIRT1 cutoff of 3.79 ng/mL for predicting the risk of MALE. Moreover, incorporating SIRT1 into predictive models significantly enhanced the accuracy of predicting adverse outcomes. Results suggest serum SIRT1 is a potential independent marker for predicting MALE and MACE in diabetic patients with CLTI undergoing LER. Further research is needed to clarify the mechanistic pathways in which SIRT1 may influence cardiovascular outcomes, and the role of this novel biomarker in the management of PAD and CLTI among patients with diabetes.
The combination CDK4/6 inhibitors (CDK4/6i) (Palbociclib, Ribociclib and Abemaciclib) with endocrine therapy (ET, i.e. aro- matase inhibitors (AI) or Fulvestrant) has significantly increased objective response rate (ORR) and progression-free survival (PFS) of first- and second-line treatments in patients with hormone receptor positive, HER2 negative (luminal) mBC. Now this combination is the standard treatment for luminal mBC. Recommendation for endocrine therapy versus chemotherapy as first-line treatment of luminal mBC is endorsed by the main international guidelines such as ASCO and ESO-ESMO guidelines. Endocrine therapy should be used as initial treatment except in cases of immediately life-threatening disease, tumors refractory to endocrine therapy, visceral crisis, or rapid progressive disease that mandate a high response rate treatment. The aim of this study is to provide real-life treatment patterns data for luminal MBC with a focus in population of Moscow
BACKGROUND & AIMS: Bulevirtide (BLV), a first-in-class entry inhibitor, is approved in Europe for the treatment of chronic hepatitis delta (CHD). BLV monotherapy was superior to delayed treatment at week (W) 48, the primary efficacy endpoint, in the MYR301 study (NCT03852719). Here, we assessed if continued BLV therapy until W96 would improve virologic and biochemical response rates, particularly among patients who did not achieve virologic response at W24.
METHODS: In this ongoing, open-label, randomized phase III study, patients with CHD (N = 150) were randomized (1:1:1) to treatment with BLV 2 mg/day (n = 49) or 10 mg/day (n = 50), each for 144 weeks, or to delayed treatment for 48 weeks followed by BLV 10 mg/day for 96 weeks (n = 51). Combined response was defined as undetectable hepatitis delta virus (HDV) RNA or a decrease in HDV RNA by ≥2 log10 IU/ml from baseline and alanine aminotransferase (ALT) normalization. Other endpoints included virologic response, ALT normalization, and change in HDV RNA.
RESULTS: Of 150 patients, 143 (95%) completed 96 weeks of the study. Efficacy responses were maintained and/or improved between W48 and W96, with similar combined, virologic, and biochemical response rates between BLV 2 and 10 mg. Of the patients with a suboptimal early virologic response at W24, 43% of non-responders and 82% of partial responders achieved virologic response at W96. Biochemical improvement often occurred independently of virologic response. Adverse events were mostly mild, with no serious adverse events related to BLV.
CONCLUSIONS: Virologic and biochemical responses were maintained and/or increased with longer term BLV therapy, including in those with suboptimal early virologic response. BLV monotherapy for CHD was safe and well tolerated through W96.
IMPACT AND IMPLICATIONS: In July 2023, bulevirtide was fully approved for the treatment of chronic hepatitis delta (CHD) in Europe based on clinical study results from up to 48 weeks of treatment. Understanding the efficacy and safety of bulevirtide over the longer term is important for healthcare providers. In this analysis, we demonstrate that bulevirtide monotherapy for 96 weeks in patients with CHD was associated with continued improvements in combined, virologic, and biochemical responses as well as liver stiffness from week 48 at both the 2 mg and 10 mg doses. Patients with suboptimal virologic responses to bulevirtide at week 24 also benefited from continued therapy, with the majority achieving virologic response or biochemical improvement by week 96.
GOV IDENTIFIER: NCT03852719.
Increasing rates of autoimmune and inflammatory disease present a burgeoning threat to human health1. This is compounded by the limited efficacy of available treatments1 and high failure rates during drug development2, highlighting an urgent need to better understand disease mechanisms. Here we show how functional genomics could address this challenge. By investigating an intergenic haplotype on chr21q22-which has been independently linked to inflammatory bowel disease, ankylosing spondylitis, primary sclerosing cholangitis and Takayasu's arteritis3-6-we identify that the causal gene, ETS2, is a central regulator of human inflammatory macrophages and delineate the shared disease mechanism that amplifies ETS2 expression. Genes regulated by ETS2 were prominently expressed in diseased tissues and more enriched for inflammatory bowel disease GWAS hits than most previously described pathways. Overexpressing ETS2 in resting macrophages reproduced the inflammatory state observed in chr21q22-associated diseases, with upregulation of multiple drug targets, including TNF and IL-23. Using a database of cellular signatures7, we identified drugs that might modulate this pathway and validated the potent anti-inflammatory activity of one class of small molecules in vitro and ex vivo. Together, this illustrates the power of functional genomics, applied directly in primary human cells, to identify immune-mediated disease mechanisms and potential therapeutic opportunities.
A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described above represent such a conversion is unknown. However, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that protriptyline hydrochloride is not approved for use in treating bipolar depression.

Protriptyline may block the antihypertensive effect of guanethidine or similarly acting compounds.

Protriptyline should be used with caution in patients with a history of seizures, and, because of its autonomic activity, in patients with a tendency to urinary retention, or increased intraocular tension.

Tachycardia and postural hypotension may occur more frequently with protriptyline than with other antidepressant drugs. Protriptyline should be used with caution in elderly patients and patients with cardiovascular disorders; such patients should be observed closely because of the tendency of the drug to produce tachycardia, hypotension, arrhythmias, and prolongation of the conduction time. Myocardial infarction and stroke have occurred with drugs of this class.

On rare occasions, hyperthyroid patients or those receiving thyroid medication may develop arrhythmias when this drug is given.

In patients who may use alcohol excessively, it should be borne in mind that the potentiation may increase the danger inherent in any suicide attempt or overdosage.
In the main phase of the study, we used a 3-group randomized study to compare the efficacy, cost-effectiveness, and ethics of a (1) voucher-based CM intervention, (2) cash-based CM intervention, and (3) non-CM intervention. Two hundred thirty seven consenting cocaine-dependent clients were randomly assigned to one of the three conditions. In this main we examined outcomes related to (1) efficacy, including UDS-confirmed abstinence and counseling attendance; (2) cost-effectiveness; and (3) ethics, including the effects on intrinsic motivation, drug use, and other high-risk behavior. This investigation addressed practical issues pertaining to the transfer of CM interventions into community-based treatment programs, and provided empirical evidence refuting ethical criticisms that have been levied against the use of cash and CM interventions.

The second phase expanded on the main study with a pilot examination of a probabilistic reinforcement CM schedule. Probabilistic methods are considered less expensive to implement yet equally efficacious, as a reward is not provided each time target behaviors are exhibited, yet similar outcomes result. In this pilot study, an additional 70 participants were randomized into either a traditional voucher-based probability reinforcement CM schedule, ("FishBowl" CM), a cash-based probability reinforcement CM schedule ("CashBowl" CM), or a standard non-CM intervention. As in the main study, we examined these conditions in terms of efficacy, associated costs and cost-effectiveness, and potential ethical risks.

The third phase of this study is a pilot that seeks to examine the efficacy of a traditional "thinning" reinforcement schedule compared to an escalating reinforcement schedule or a treatment-as-usual (non-contingency management control) condition in improving the during-treatment and post-treatment outcomes of cocaine dependent outpatients in community-based treatment. Participants will be randomly assigned to one of three treatment conditions: Escalating CM Condition (n = 15), Traditional ("thinning") CM Condition (n = 15), and Non-CM Control Condition (n = 15). The intervention will last a total of 16 weeks. Participants assigned to each of the experimental conditions will receive different contingency and reward procedures during study weeks 1-12; they will receive identical contingency and reward procedures during study weeks 13-16. Participants assigned to the control condition will not receive any contingencies or rewards during the entire 16 week study. As in the main study, we will examine these conditions in terms of efficacy, associated costs and cost-effectiveness, and potential ethical risks.
Provided herein are methods for the induction of hypothermia and the treatment of clinical insults in a subject through the administration of a regulated hypothermic multidrug combination.  The compositions or multidrug combinations of the invention comprise a regulated hypothermic compound or a dopamine receptor agonist; a vasoactive compound; and an antiarrhythmic compound or a serotonin 5-HT3 receptor antagonist. Additional agents can be included in the composition including at least one of an antioxidant, a vitamin, N-acetylcysteine, and an antihyperglycemic compound. The invention further recognizes that a two phase delivery of multidrug combinations, a rapid infusion of the composition to induce hypothermia followed by a period of slow infusion to maintain the hypothermic state for a sustained period of time. Using the two phase delivery method of the invention, the composition may comprise ethanol and, optionally, at least one of a vasoactive compound, an antiarrhythmic compound, a serotonin 5-HT3 receptor antagonist, an antioxidant, a vitamin, N-acetylcysteine, and an antihyperglycemic compound.  This two phase delivery method can be used to deliver any of the compositions of the invention and provides significant benefits to a patient.