anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
A pharmaceutical compsn. for the treatment of diseases of the circulatory organs contains a piperazine deriv. of formula I (where R1 is lower alkyl; R2 is H or lower alkyl; A is C4-6 linear or branched alkylene; X = halo) or its nontoxic salts as the active component (0.1-100, pref. 1-50 mg per daily close), dispersed with the usual carriers. The prods. esp. useful for ischemic cardiac disease and vasodilation of the periphery blood vessels, are prepd. by the reaction of II and 6 X-A-COOR2.
FIELD: veterinary microbiology, veterinary science. SUBSTANCE: invention proposes the new strain of bacterium Klebsiella pneumoniae that is deposited in VGNKI at = 23 MGAVMiB-DEP. The proposed strain is isolated in laboratory of infectious pathology and biotechnology MGAVMiB from newborn calf feces in 1987 year. The strain is a producer of α- and β-hemolysins. The new strain exhibits high productivity, 50-60 billion cells in 1 ml, by optic turbidity standard GISK named for K.A.Tarasevich. The proposed strain can be used in veterinary for producing vaccines against klebsiellosis in agricultural young stock and for preparing immune preparations used for prophylaxis and treatment of acute intestine diseases in animals. EFFECT: valuable properties of strain and vaccines.
Neurofibromatosis type 1 (NF1) is one of the most common inherited tumor predisposition syndromes, affecting approximately 1 in 3000 people worldwide. NF1 is an autosomal dominant condition caused by pathogenic variants in the NF1 tumor suppressor gene resulting in a deficiency in the protein neurofibromin resulting in constitutive activation of the Ras oncoprotein and subsequent tumors. Plexiform neurofibromas (PN) are a complex of Schwann cells, fibroblasts, endothelial cells, and mast cells, which can cause disfigurement, pain, life threatening complications and can undergo malignant transformation. These tumors are refractory to most therapeutic approaches including chemotherapy, radiation, and surgery; thus, novel treatment interventions are urgently needed. Two agents have shown substantial activity in shrinking PN in adults with symptomatic or progressive PN in clinical trials through the NCI and the Congressionally Directed Medical Research Programs (CDMRP) Neurofibromatosis Clinical Trials Consortium (NFCTC): the MEK inhibitor selumetinib and the multi-tyrosine kinase inhibitor cabozantinib. Unfortunately, confirmed objective responses are not uniformly achieved and the degree of volumetric tumor reduction might be improved in patients with partial response as only a small percentage of patients have deep responses. In an open-label, phase 2 study evaluating selumetinib for children with inoperable PN, 68% of participants treated with selumetinib achieved a partial response (defined as a reduction in tumor volume by ≥20%). In a phase 2 trial (NCT02101736) of cabozantinib in participants \>16 years old with symptomatic or progressive PN, 42% of patients had a partial response. Of note, dose reductions and/or discontinuation of treatment was common in both studies, with 28% of patients in the selumetinib study requiring dose reductions and 10% eventually requiring permanent discontinuation of treatment. In the cabozantinib study 42% of the participants required dose reductions or discontinuation of therapy due to either dose-limiting toxicity or low-grade adverse events (AEs) perceived to be intolerable.

Based on the demonstrated significant clinical activity of both selumetinib and cabozantinib as monotherapies in clinical trials and the demonstrated activity of these agents in reduced doses in the preclinical studies, as well as the non-overlapping toxicity profiles, the study will assess the tolerability and efficacy of selumetinib and cabozantinib in combination in patients with NF1 ≥16 years old with progressive or symptomatic PN in a phase 1/1b/2 clinical trial.
Epilepsy is characterized by abnormal neuronal firing in the brain. Several therapeutic strategies exist for epilepsy; however, several patients remain poorly treated. Therefore, the development of effective treatments remains a high priority in the field. Neuroactive steroids can potentiate extra-synaptic and synaptic GABAA receptors, thereby providing therapeutic benefits relative to benzodiazepines. This research study investigated the therapeutic effectiveness and underlying mechanisms of LPM682000012, a new synthetic neuroactive steroid-positive allosteric modulator (PAM) of GABAA receptors employed for treating epilepsy. Acute and chronic rat epilepsy models were established to identify the anti-seizure potency of LPM682000012. The dose-dependent sedative effects of LPM682000012 and Ganaxolone in normal rats were evaluated, which revealed that they both dose-dependently alleviated acute epileptic seizure in the pentylenetetrazol (PTZ)-mediated seizure model. Furthermore, LPM682000012 indicated an enhanced safety profile than Ganaxolone. Moreover, LPM682000012 also indicated therapeutic effects in the kainic acid (KA)-induced chronic spontaneous seizure model. Morphologically, LPM682000012 decreased neuronal loss in the hippocampal CA1 and CA3 regions and increased dendritic spine density in the CA1 region. In addition, mechanical analyses, including transcriptomics, Western blot, and proteomics analyses, revealed that the Serpina3n/NF-κB signaling pathway was up-regulated in epileptic rat hippocampal tissue, and LPM682000012 treatment reversed these changes. In summary, this report demonstrated that the novel neurosteroid GABAA PAM LPM682000012 activated the synaptic and extra-synaptic GABAA receptors and alleviated KA-induced neuronal loss and synaptic remodeling, potentially by down-regulating the Serpina3n/NF-κB signaling pathways. The results provide evidence that LPM682000012 is a potential anti-seizure pharmacotherapy candidate for epilepsy and warrants further research.
BACKGROUND: Watertight closure of dura mater after intracranial surgery can avoid cerebrospinal fluid leakage and central nervous system infection and herniation. When primary closure is not possible, the pericranium is the preferential choice. When it is not available, a dural substitute becomes necessary. Bovine pericardium treated with polyethylene glycol and ethanol is herein tested as a dural substitute.
METHODS: A pilot study comparing bovine pericardium with pericranium in supratentorial neurosurgery was performed.
RESULTS: Twenty patients were initially allocated into a bovine pericardium group (group 1) or a pericranium group (group 2). Three patients from group 1 and 2 from group 2 had a loss of follow-up, being excluded. In the remaining 15 patients, epidemiological analysis demonstrated a male:female ratio of 3:4 and 4:4 for groups 1 and 2. Ages varied from 28 to 68 (Mean = 49.6) in group 1 and 40-80 (Mean = 61.2) in group 2, with a mean difference of 11.68 years (P = 0.09). Two cases of surgical site infection and 1 of hydrocephalus were observed. Although the calculated relative risk for complications was higher in group 1 (Relative Risk = 1.08), Fisher exact test demonstrated no statistically significant difference between groups (P = 1.00). Procedure mean time was 23 minutes and 11 seconds in group 1 versus 27 minutes and 55 seconds in group 2 (P = 0.47). Mean graft area was 13.17 and 6.23 cm2 in groups 1 and 2 (P = 0.02).
CONCLUSIONS: Bovine pericardium treated with polyethylene glycol and ethanol was comparable to pericranium as a dural substitute. More studies are encouraged to certify our findings.
We examined the association between mean birth weight (BW) differences and perfluorohexane sulfonate (PFHxS) exposure biomarkers.We fit a random effects model to estimate the overall pooled effect and for different strata based on biomarker sample timing and overall study confidence. We also conducted an analysis to examine the impact of a continuous measure of gestational age sample timing on the overall pooled effect.We detected a -7.9 g (95% CI -15.0 to -0.7; pQ=0.85; I2=0%) BW decrease per ln ng/mL PFHxS increase based on 27 studies. The 11 medium confidence studies (β=-10.0 g; 95% CI -21.1 to 1.1) showed larger deficits than 12 high (β=-6.8 g; 95% CI -16.3 to 2.8) and 4 low confidence studies (β=-1.5 g; 95% CI -51.6 to 48.7). 10 studies with mid-pregnancy to late-pregnancy sampling periods showed smaller deficits (β=-3.9 g; 95% CI -17.7 to 9.9) than 5 post-partum studies (β=-28.3 g; 95% CI -69.3 to 12.7) and 12 early sampling studies (β=-7.6 g; 95% CI -16.2 to 1.1). 6 of 12 studies with the earliest sampling timing showed results closer to the null.Overall, we detected a small but statistically significant BW deficit across 27 studies. We saw comparable BW deficit magnitudes in both the medium and high confidence studies as well as the early pregnancy group. Despite no definitive pattern by sample timing, larger deficits were seen in postpartum studies. We also saw results closer to the null for a subset of studies restricted to the earliest biomarker collection times. Serial pregnancy sampling, improved precision in gestational age estimates and more standardised reporting of sample variation and exposure units in future epidemiologic research may offer a greater understanding of the relationship between PFHxS on BW and any potential impact of pregnancy haemodynamics.
COMPOSITION AND METHOD FOR REDUCING WRINKLES                  Abstract of the Disclosure Stable  retinol  compositions  are  disclosed.   The compositions comprise retinol, a volatile silicone and a mutual solvent for the retinol and silicone.  Preferred compositions contain retinol, cyclomethicone and ethanol.      Where the retinol level in the compositions is between 0.005 and 1.0 weight percent, the compositions may be topically applied to the skin in areas where fine lines, wrinkles or other signs of aging exist.  Such topical application results in a reduction in wrinkles and fine lines and improves skin quality.  Where the compositions contain more than 0.005 to 1.0 weight percent retinol they may be diluted with cosmetically acceptable carriers or vehicles,  preferably water  in oil emulsions to reduce the retinol level and topically applied.
The optimal approach for aortic valve replacement in adults with an anticipated life expectancy greater than fifteen years remains unclear. Mechanical and bioprosthetic valves, while often used, have specific downfalls. Mechanical valves require lifelong anticoagulation usage and bioprosthetic tissue valves have a limited lifespan. The Ross procedure (pulmonary autograft replacement) is the only operation which replaces the diseased aortic valve with a living substitute. Concerns over increased surgical risk and potential long-term failure have shown decreased use of this procedure. However, recent publications from expert centers have shown, in the current era the Ross procedure can be reliably performed safely and reproducibly in selected patients. Furthermore, an increasing body of evidence suggests the Ross procedure is associated with better long-term outcomes compared with conventional aortic valve replacement (AVR) in young and middle-aged adults (jamc 2018,72:2761-77. This standardized prospective long-term outcome analysis will help reaffirm these findings via a multicenter patient cohort and describe the best practices/techniques for stabilization of the autograft and right ventricular outflow tract reconstruction.
For treatment-experienced participants, SOF was given in a dose of 400 mg/day + SMV orally as a single 150 mg q.d. capsule.
Compositions and methods for treating lysosomal storage diseases are disclosed. Lysosomal dysfunction is usually the result of deficiency of a single enzyme necessary for the metabolism of lipids, glycoproteins (sugar containing proteins) or mucopolysaccharides which are fated for breakdown or recycling. The compositions contain triplex-forming molecules which can be used to induce site-specific homologous recombination in mammalian cells when combined with donor DNA molecules, by stimulating cellular DNA synthesis, recombination, and repair mechanisms. The methods are particular useful for correcting point mutations in genes associated with lysosomal storage diseases such as Gaucher' s disease, Fabry disease, and Hurler syndrome. Methods for determining the frequency of target gene repair and assessing the restoration of the enzymatic activity of corrected polypeptides are also disclosed. Ex vivo and in vivo methods of gene correction in patients are also provided.
Data in the wait-list control group will be collected at the same time intervals as the intervention group. After Time 3 data collection, they will be offered the Phase I intervention (12 weekly sessions).
Microsurgical toe transfer has become a gold standard option for amputated digit reconstruction. It can be used to correct almost any thumb defect. However, for optimal functional and esthetic results, proper initial care, preoperative planning, proper selection of suitable techniques, adjunct or secondary procedures and proper, postoperative rehabilitation are important.

The transfer of a toe to replace an amputated thumb represents one of the first applications of microsurgical techniques, yet to this day remains an epitome of reconstructive surgery, restoring critical function and form to the hand-injured patient. While techniques have greatly evolved to permit the treatment of multiple finger amputations, dystrophic nails and pulps, and traumatized or arthritic joint, the amputated thumb retains its status among the most indubitable indications for toe transfer. Microsurgical techniques have been refined to such a degree that almost any ablative deformity of the thumb could be corrected with some form of toe transfer. The question, therefore, is not if a defect could be reconstructed, but whether the patient is willing to undergo reconstruction. The concepts of "adequate function" and "optimal function" are therefore of central importance when discussing treatment options with a patient. Obviously, these parameters will be different for each patient depending upon his/her vocation, avocations, and desires. For many people, adequate function might be expected with an amputation that retains some length of the proximal phalanx (assuming sufficient soft tissue coverage is present or can be provided). However, for patients who require full length of their thumb, or who desire optimal rather than adequate function, toe transfer should be considered.

At present, the decision to use a particular toe transfer technique is mostly based on the surgeon's preference and training. The current data are inadequate to make any comments with regards to donor site morbidity. Till such data are available, an evidence-based recommendation for the superiority of a specific type of toe-to-thumb transfer cannot be made. We hypothesis that partial toe transfer provides the best aesthetic and functional reconstruction and the least donor site morbidity amongst all other types of transfers.
Visceral hypersensitivity resulting from compromised gut barrier with activated immune system is a key feature of irritable bowel syndrome (IBS). Corticotropin-releasing factor (CRF) and Toll-like receptor 4 (TLR4) activate proinflammatory cytokine signaling to induce these changes, which is one of the mechanisms of IBS. As activation of the NLRP3 inflammasome by lipopolysaccharide (LPS) or TLR4 leads to release interleukin (IL)-1β, the NLRP3 inflammasome may be involved in the pathophysiology of IBS. Tranilast, an anti-allergic drug has been demonstrated to inhibit the NLRP3 inflammasome, and we evaluated the impact of tranilast on visceral hypersensitivity and colonic hyperpermeability induced by LPS or CRF (IBS rat model). Visceral pain threshold caused by colonic balloon distention was measured by monitoring abdominal muscle contractions electrophysiologically. Colonic permeability was determined by quantifying the absorbed Evans blue within the colonic tissue. Colonic protein levels of NLRP3 and IL-1β were assessed by immunoblot or ELISA. Intragastric administration of tranilast (20-200 mg/kg) for 3 days inhibited LPS (1 mg/kg)-induced visceral hypersensitivity and colonic hyperpermeability in a dose-dependent manner. Simultaneously, tranilast also abolished these alterations induced by CRF (50 µg/kg). LPS increased colonic protein levels of NLRP3 and IL-1β, and tranilast inhibited these changes. β-hydroxy butyrate, an NLRP3 inhibitor, also abolished visceral hypersensitivity and colonic hyperpermeability caused by LPS. In contrast, IL-1β induced similar GI alterations to LPS, which were not modified by tranilast. In conclusion, tranilast improved visceral pain and colonic barrier by suppression of the NLRP3 inflammasome in IBS rat models. Tranilast may be useful for IBS treating.
In parotid gland cancer (PGC), cervical lymph node metastasis (LNM) and intra-parotid LNM are known as significant indicators of poor prognosis. However, the topography of LNM in the affected parotid gland and the lymphatic progression of PGC has never been explored in detail. This was a retrospective analysis of data from 423 patients with previously untreated primary PGC (2005 to 2020), excluding patients with squamous cell carcinoma, lymphoma or metastatic disease in the parotid gland. The pattern of LNM was analyzed by neck sub-level and parotid sub-site. Using the conditional probability of neck level involvement, a probability diagram was plotted on several thresholds to visualize the sequential progression of LNM in PGC. The pattern of LNM progression was found to be similar between low- and high-grade pathology, but the incidence differed significantly (8.0% vs. 45.4%). Intra-parotid LNs and level IIa LNs were the most common sites (57.3% and 61.0%) of LNM in PGC, followed by level III (31.7%), Ib (25.6%), IV (22.0%), IIb (20.7%) and Va (20.7%) LNM. In intra-parotid LNs, the incidence of LNM in the deep parotid LNs was relatively low (9.4%); most intra-parotid LNMs were observed in the superficial parotid (90.6%) and peri-tumoral (in contact with the tumor) (31.3%) LNs. LNM to levels Ia, Vb and contra-lateral LNM occurred only in the very late stage. Our results provide detailed information about LNM progression in PGC at the sub-level and can help clinicians decide the treatment extent, including surgery or radiation.
Prepare solution at the time of dispensing by adding the water in two portions to the bottle as follows: Loosen powder by tapping the bottle, add about half the water, and shake well. Add the remaining water and shake well to complete solution. Each teaspoon (5 mL) will contain Penicillin V Potassium equivalent to 125 mg or 250 mg of Penicillin V. 

Note: Shake the oral solution well before using.

Store the reconstituted solution in a refrigerator. Discard any unused portion after 14 days. Keep the bottle tightly closed.
ATTN uses 10- video-based telemedicine sessions to deliver general patient education specific to young children. Similar to REDCHiP, all ATTN sessions last 45-60 minutes.
SAPHRIS may induce orthostatic hypotension and syncope in some patients, especially early in treatment, because of its α1-adrenergic antagonist activity. In short-term schizophrenia trials, syncope was reported in 0.2% (1/572) of patients treated with therapeutic doses (5 mg or 10 mg twice daily) of SAPHRIS, compared to 0.3% (1/378) of patients treated with placebo. In short-term bipolar mania trials, syncope was reported in 0.3% (1/379) of patients treated with therapeutic doses (5 mg or 10 mg twice daily) of SAPHRIS, compared to 0% (0/203) of patients treated with placebo. During pre-marketing clinical trials with SAPHRIS, including long-term trials without comparison to placebo, syncope was reported in 0.6% (11/1953) of patients treated with SAPHRIS.

Four normal volunteers in clinical pharmacology studies treated with either intravenous, oral, or sublingual SAPHRIS experienced hypotension, bradycardia, and sinus pauses. These spontaneously resolved in 3 cases, but the fourth subject received external cardiac massage. The risk of this sequence of hypotension, bradycardia, and sinus pause might be greater in nonpsychiatric patients compared to psychiatric patients who are possibly more adapted to certain effects of psychotropic drugs.

Patients should be instructed about nonpharmacologic interventions that help to reduce the occurrence of orthostatic hypotension (e.g., sitting on the edge of the bed for several minutes before attempting to stand in the morning and slowly rising from a seated position). SAPHRIS should be used with caution in (1) patients with known cardiovascular disease (history of myocardial infarction or ischemic heart disease, heart failure or conduction abnormalities), cerebrovascular disease, or conditions which would predispose patients to hypotension (dehydration, hypovolemia, and treatment with antihypertensive medications); and (2) in the elderly. SAPHRIS should be used cautiously when treating patients who receive treatment with other drugs that can induce hypotension, bradycardia, respiratory or central nervous system depression [see Drug Interactions (7)]. Monitoring of orthostatic vital signs should be considered in all such patients, and a dose reduction should be considered if hypotension occurs.
Women will receive standard of care Quit Smoking Now tobacco education and support plus prize-based contingency management. Their smoking status will be monitored from quit date through 3 months postpartum via carbon monoxide and salivary cotinine levels. Women will earn chances to win prizes each time they test negative for smoking according to biochemical measures.
Safety and effectiveness have not been established in pediatric patients with IBS-C, pediatric functional constipation (PFC), and OIC. 

Efficacy was not demonstrated for the treatment of PFC in patients 6 years of age and older in a 12 week, randomized, double-blind, placebo-controlled trial conducted in 606 patients 6 to 17 years with PFC comparing lubiprostone to placebo. The primary efficacy endpoint was an overall response based on spontaneous bowel movement frequency over the duration of the trial; the treatment difference from placebo was not statistically significant. In this age group, adverse reactions to lubiprostone were similar to those reported in adults. In a 36-week, long-term safety extension trial after approximately 9 months of treatment with lubiprostone, a single case of reversible elevation of ALT (17-times upper limit of normal [ULN]), AST (13-times ULN), and GGT (9-times [ULN]) was observed in a child with baseline elevated values (less than or equal to 2.5-times ULN).

Juvenile Animal Toxicity Data

In a 13-week oral toxicity study in juvenile rats, a significant decrease in total bone mineral density was observed in female pups at 0.5 mg/kg/day; in male pups, a significantly lower cortical thickness at the tibial diaphysis was observed at 0.5 mg/kg. The 0.5 mg/kg/day dose is approximately 101 times the maximum recommended adult dose of 48 mcg/day, based on body surface area (mg/m2).
The present invention discloses alkaloid liposome in vinca and a preparation technology thereof. The present invention belongs to the field of chemical pharmacy. The alkaloid liposome in vinca is prepared from alkaloid in vinca, liposome material and an oxidation inhibitor, and the proportion (w/w) of medicine to fat is from 0.05 to 0.2:1, wherein the liposome material contains phospholipid and cholesterol, the molar ratio of the phospholipid to the cholesterol is 40 to 60:30 to 50 mol%, the oxidation inhibitor is prepared from alpha-tocopherol and desferal, and the concentration of alpha-tocopherol and the concentration of desferal are respectively from 0.015 to 0.025 mg/ml and from 0.10 to 0.20 mg/ml. The preparation technology comprises the following steps: step (1), multi-layer liposome is prepared; step (2), small one-layer liposome is prepared; step (3), the alkaloid liposome in vinca is prepared. The present invention has the advantages of little toxicity of finished products, high entrapment efficiency, high stability and simple and convenient operation of the. Industrial preparation can be carried out.