anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
In the laboratory classroom clinical trials in children (Studies 1 and 2), both methylphenidate hydrochloride extended-release tablets once daily and methylphenidate three times daily increased resting pulse by an average of 2 to 6 bpm and produced average increases of systolic and diastolic blood pressure of roughly 1 to 4 mm Hg during the day, relative to placebo. In the placebo-controlled adolescent trial (Study 4), mean increases from baseline in resting pulse rate were observed with methylphenidate hydrochloride extended-release tablets and placebo at the end of the double-blind phase (5 and 3 beats/minute, respectively). Mean increases from baseline in blood pressure at the end of the double-blind phase for methylphenidate hydrochloride extended-release tablets and placebo-treated patients were 0.7 and 0.7 mm Hg (systolic) and 2.6 and 1.4 mm Hg (diastolic), respectively. In one placebo-controlled study in adults (Study 6), dose-dependent mean increases of 3.9 to 9.8 bpm from baseline in standing pulse rate were observed with methylphenidate hydrochloride extended-release tablets at the end of the double-blind treatment vs. an increase of 2.7 beats/minute with placebo. Mean changes from baseline in standing blood pressure at the end of double-blind treatment ranged from 0.1 to 2.2 mm Hg (systolic) and ­0.7 to 2.2 mm Hg (diastolic) for methylphenidate hydrochloride extended-release tablets and was 1.1 mm Hg (systolic) and -1.8 mm Hg (diastolic) for placebo. In a second placebo-controlled study in adults (Study 5), mean changes from baseline in resting pulse rate were observed for methylphenidate hydrochloride extended-release tablets and placebo at the end of the double-blind treatment (3.6 and -1.6 beats/minute, respectively). Mean changes from baseline in blood pressure at the end of the double–blind treatment for methylphenidate hydrochloride extended-release tablets and placebo-treated patients were -1.2 and -0.5 mm Hg (systolic) and 1.1 and 0.4 mm Hg (diastolic), respectively [see Warnings and Precautions (5.1)].
The safety and efficacy of vinorelbine in combination with cisplatin was evaluated in two randomized, multicenter trials. 

Cisplatin 100mg/m2

Study 1 was a randomized, multicenter, open-label trial of vinorelbine plus cisplatin and cisplatin alone for the treatment of stage IV or stage IIIb NSCLC in patients with malignant pleural effusion or multiple lesions in more than one lobe of the ipsilateral lung who had not received prior chemotherapy. A total of 432 patients were randomized 1:1 to receive either vinorelbine 25 mg/m2 on Day 1 then every week of each 28-day cycle plus cisplatin 100 mg/m2 administered on Day 1 of each 28-day cycle (N=214) or single agent cisplatin 100 mg/m2 on Day 1 of each 28-day cycle (N=218). 

Patient demographics and disease characteristics were similar between arms. Of the overall study population, the median age was 64 (range 33 to 84), 66% were male, 80% were White, 92% had stage IV disease and 8% stage IIIB, 53% had adenocarcinoma, 21% squamous cell, 14% large cell histology. The major efficacy outcome measure was overall survival. The efficacy results are presented in Table 7 and Figure 1. 

Figure 1: Overall Survival Vinorelbine / Cisplatin versus Single Agent Cisplatin

Cisplatin 120mg/m2

Study 2 was a randomized, 3-arm, open-label, multicenter trial of vinorelbine plus cisplatin, vindesine plus cisplatin and vinorelbine as a single agent for the treatment of patients with stage III or IV NSCLC who had not received prior chemotherapy. The study was conducted in Europe. A total of 612 patients were randomized 1:1:1 to receive vinorelbine 30 mg/m2 every week of a 6-week cycle plus cisplatin 120 mg/m2 on Day 1 and Day 29, then every 6 weeks thereafter (N=206); and vindesine 3 mg/m2 for 6 weeks, then every other week thereafter plus cisplatin 120 mg/m2 on Days 1 and Day 29, then every 6 weeks thereafter (N=200) or vinorelbine 30mg/m2 every week of a 6-week cycle (N=206). The main efficacy outcome measure was to compare overall survival between vinorelbine plus cisplatin and vindesine plus cisplatin. The other efficacy outcome measure was to compare overall survival in the better of the two combination regimens to that of vinorelbine as a single agent. 

Patient demographics were in general similar between arms: the median age of the overall population was 60 years (range 30 to 75), 90% were male, 78% had WHO performance status of 0 or 1. Tumor characteristics were in general similar with the exception of histologic subtype of NSCLC. Adenocarcinoma was the histologic subtype in 32% of patients in the vinorelbine plus cisplatin arm, 40% of patients in vindesine plus cisplatin arm and 28% of patients on the vinorelbine arm. Ten percent of the patients had stage IIIA disease, 28% stage IIIB and 50% stage IV. Twelve percent of the patients had received prior surgery or radiotherapy. 

The efficacy results of Study 2 are presented in Table 8.
The invention relates to a liquid for strengthening bone and alleviating pain. The invention is characterized in that the liquid for strengthening bone and alleviating pain does not have toxic or side effect, can be easily absorbed, and maintain the original effects of the drugs, thereby enhancing the utilization ratio of drugs. The traditional Chinese medicine extracting liquid has the advantages of strong drug potency, centralized dose, long acting time, good curative effect and quick effect taking, can not easily relapse after treatment, and performs the functions of interrupting malignant pathological cycles, inhibiting hyperosteogeny, resisting inflammations, promoting the subsidence of swelling, alleviating pain and softening bone spurs. The liquid for strengthening bone and alleviating pain can tonify the liver and kidney, strengthen the bones and muscles and complement vitality and marrow, thereby fundamentally ensuring no relapse after the ostealgia is cured. Since ethanol is used as the carrier, the liquid for strengthening bone and alleviating pain tastes acrid and hot, can dredge collaterals and channels, and has quick transdermal action. Thus, under the synergistic actions of the medicines and the ethanol, the liquid for strengthening bone and alleviating pain can get curative effect instantly.
<P>PROBLEM TO BE SOLVED: To provide a hair cosmetic composition capable of keeping stability of a persulfate and suppressing damage to the hair even when reducing the amount of a component for suppressing decomposition of the persulfate.  <P>SOLUTION: The hair cosmetic composition comprises (A) a persulfate, (B) a solid-like alkali agent, (C) trisodium N-hydroxyethylethylenediaminetriacetate and (D) cyclodextrins or dried starch. It is preferable that the mass ratio of the component (C) to the component (A) is 0.00125-0.125. It is preferable that the mass ratio of the component (D) to the component D is 0.00125-0.125. The hair cosmetic composition is a solid-like composition used for decoloration of the hair.  <P>COPYRIGHT: (C)2006,JPO&NCIPI
The purpose of this single-arm, interventional pilot study is to evaluate the effect of psychological stress intervention for patients with chronic urticaria, as many of these patients report heightened levels of stress before and/or after the onset of the urticaria. Participants will meet individually with a University of Mississippi Medical Center psychiatry resident for one hour once a week for six consecutive weeks to be educated on psychological stress intervention techniques. There is no control group for this pilot study. All participants will complete a packet of psychological and dermatological questionnaires before the first session with the psychiatry resident and one week after the final session. All participants will record daily 1) their urticaria symptoms and 2) the type and number of medications taken for his/her chronic hives. If psychological stress intervention proves to be effective, then this therapeutic modality would benefit patients with chronic urticaria, while avoiding addition and/or continuation of medications that may have significant adverse side effects.
The present invention claims and discloses a pharmaceutical composition suitable for oral administration, in form of an emulsion pre-concentrate, comprising(i) one or more NO-releasing NSAID(s);(ii) one or more surfactants, of which at least one is phospholipid;said composition forming an in-situ oil-in-water emulsion upon contact with gastrointestinal fluids. The composition may optionally also comprise an additional oil or semi-solid fat. Further, one or more short-chain alcohols can optionally be included in the composition. Also within the scope of the invention is a combination with a proton pump inhibitor. The pharmaceutical composition is useful in the treatment of pain and inflammation. Further within the scope of the invention is kit comprising a pharmaceutical composition according to the invention in a unit dosage form, in combination with a proton pump inhibitor, and said proton pump inhibitor is enteric coated.
Given the background of optimizing financial and personnel resources while aligning with patient needs, the concept of same-day discharge following pulmonary vein isolation (PVI) appears attractive. However, a non-selective approach to different strategies is inappropriate, as is often the case in medicine. A "one size fits all" approach is therefore not advisable for outpatient PVI. Instead, the primary focus should be on identifying which patients can safely and effectively undergo PVI in an outpatient setting and which patients would benefit from inpatient care. Both procedural and patient-specific criteria should be considered in this context. In addition, structural prerequisites must also be met. Ultimately, the decision as to whether outpatient PVI is feasible should remain with the treating physician and the patient.
This is an open-label (all people involved know the identity of the intervention), single arm, multicenter (when more than one hospital or medical school team work on a medical research study), prospective study (study following participants forward in time) to evaluate the efficacy and safety of OROS methylphenidate in participants with ADHD (behavior disorder originating in childhood in which the essential features are signs of developmentally inappropriate inattention, impulsivity, and hyperactivity). The study duration will be of 12 weeks per participant, which is divided into 2 parts Screening (within 14 days before study commences on Day -1) and treatment (8 weeks and will include titration period \[from the initiation of the study treatment to determination of the individual's maintenance dose\] and maintenance period \[at least 4 weeks after determination of maintenance dose\]). Participants will receive initial dose depending on their body weight. OROS methylphenidate hydrochloride (HCL) will be given orally once daily at an initial dose of 18 milligram (mg) for participants below 30 kilogram (kg) and 27 mg for those over 30 kg of body weight. The dose will be increased by 9 mg or 18 mg every week for up to Week 8, followed by a maximum maintenance dose of 54 mg orally once daily up to Week 12 during which the dose can be decreased by 9 mg depending on tolerability. Efficacy will be evaluated by Korean Version, ADHD Rating Scale (K-ARS) total score and Clinical Global Impression)-Severity / Impression rating scale CGI-S/I. Participants safety will be monitored throughout the trial.
The BTX-A group will receive onabotulinumtoxinA (Botox®, Allergan) with mandatory muscles getting 300 units and optional muscles getting up to 100 additional units (maximum dose of 400 units) (14) delivered with a 27-gauge (0.45 mm) beveled needle. Target muscles will be identified by ultrasound imaging or muscle stimulation. Local anesthesia will not be used. Patient positioning will be standardized.
BACKGROUND: We present a case of an inflammatory myofibroblastic tumor cured with a short period of steroid administration, a treatment previously unreported for such cases.
CASE PRESENTATION: A 49-year-old man had a chief complaint of chest pain for more than 3 days. Computed tomography (CT) revealed a tumoral lesion suspected to have infiltrated into the right first rib and intercostal muscles, with changes in lung parenchymal density around the lesion. The maximal standardized uptake value on 18 F-fluorodeoxyglucose positron emission tomography/computed tomography was high (16.73), consistent with tumor presence. CT-guided biopsy revealed an inflammatory myofibroblastic tumor with no distant metastases. Surgery was indicated based on the disease course. However, he had received an oral steroid before the preoperative contrast-enhanced CT scan due to a history of bronchial asthma, and subsequent CT showed that the tumor shrank in size after administration; he has been recurrence-free for more than a year.
CONCLUSIONS: Surgery is still the first choice for inflammatory myofibroblastic tumors, as the disease can metastasize and relapse; however, this condition can also be cured with a short period of steroid therapy.
OBJECTIVES: To investigate the effects of bladder neck incision (BNI) and primary valves ablation on long-term kidney and bladder function in children with posterior urethral valves (PUV) and bladder neck hypertrophy (BNH).
PATIENTS AND METHODS: From 1997 to 2016, a total of 1381 children with PUV were referred to our tertiary hospital. Of these patients, 301 PUV patients with bladder neck hypertrophy need concurrent BNI and valve ablation. All patients were followed up every 3-6 months on regular basis in first 2 post-surgical years and annually then after. The paired t-test and chi-square test were used to perform statistical analysis with p value < 0.05 defined as the level of significance.
RESULTS: Mean age at diagnosis was 7.22 ± 2.45 months (ranging from 7 days to 15 months) with a mean follow-up of 5.12 ± 2.80 years. The incidence of hydronephrosis was decreased from 266 (88.3%) at the baseline to 73 (24.3%) patients in long-term follow-up. At baseline, 188 (62.5%) patients were diagnosed with VUR, which decreased to 20 (6.6%) individuals at the end of follow-up. Bladder and renal function were improved in follow-ups following concomitant PUV ablation and BNI. No Myogenic failure was depicted in all patients with BNH. No ureteric reimplantation was needed during the two decades follow-up.
CONCLUSION: Simultaneous valve ablation with BNI may present further profits in children with PUV and BNH particularly cases of BNH with poor bladder function at the time of presentation. This method can improve the results of urodynamic and imaging studies after the surgery. We hypothesize every child with PUV presentation who has concurrent vesicoureteral reflux, CKD or persistent hydrourethronephrosis may suffer from secondary bladder neck obstruction. This secondary bladder outlet obstruction must be managed through BNI as the surgical relief.
Conventional Treatment and Phonophoresis Patients in this group will receive phonophoresis treatment in addition to a home exercise program and splint. A US device (Intelect 2776 Combo; Chattanoga Group, Inc, Chattanoga, TN) will be used for phonophoresis. The gel containing 10% naproxen will be mixed with aquasonic us gel to better deliver the drug through the body. Continuous mode at 1watt/cm2 1mhz frequency will be applied around the lateral epicondyle for 5 minutes. Sessions will be applied 5 sessions per week for 2 weeks.
The present disclosure provides ribonucleic acid (RNA) polynucleotides encoding replicative viral genomes that, when introduced into a subject, induce active viral replication. The RNA may be provided in naked form or with an artificial RNA delivery system. The viral genome may be the full length genome of an attenuated strain. For example, the RNA can encode an attenuated chikungunya virus or a yellow fever virus. The artificial RNA delivery system may be a lipid particle, such as a Lipid Nanoparticle (LNP), a Nanostructured Lipid Carrier (NLC), or a Cationic Nanoemulsion (CNE). The present disclosure also provides methods of inducing an immune response comprising protective immunity by: the RNA polynucleotide encoding the replicating viral genome is administered to the subject in an amount sufficient to cause viral replication in the subject. The immune response may include induction of neutralizing antibodies at levels comparable to those of the vaccinated attenuated virus.
FIELD: organic chemistry, biochemistry, medicine, pharmacy. SUBSTANCE: invention relates to novel thienopyrimidines and their physiologically acceptable salts with inhibitory effect with respect to phosphodiesterase V (PDE V) that can be used for control of cardiovascular system diseases and for treatment and/or therapy of potency disorder. Invention relates also to method of their synthesis and pharmaceutical composition based on thereof. New compounds correspond to the general formula (I)   where each of R 1 , R 2  means independently each of other A or Hal; or R 1 , R 2  mean in common alkylene with 3-5 C-atoms; each of R 3 , R 4  means independently each of other H, A, OA or Hal; R 3  and R 4  form in common also -O-CH 2 -CH 2 -, -O-CH 2 -O- or -O-CH 2 -CH 2 -O-; A means alkyl with 1-6 carbon atoms; X means 5-7-membered saturated heterocyclic ring mono- or disubstituted with residue R 5 , or 5-7-membered unsaturated or saturated isocyclic ring mono- or disubstituted with residue R 5 ; R 5  means COOH, CH 2 COOH or CH 2 CH 2 COOH; Hal means F, Cl, Br or J and n = 0, 1, 2 or 3. Invention relates also to method of synthesis of compounds of the formula (I) or their physiologically acceptable salts where X means saturated 5-7- membered heterocyclic ring mono- or disubstituted with residue R 5  and bound through N atom. Method involves interaction of compound of the formula (II)   where R 1 , R 2 , R 3 , R 4  and n have values indicated above and L means Cl, Br, OH, SCH 3  or reactive esterified OH-group with saturated 5-7-membered heterocyclic ring mono- or disubstituted with residue R 5  where R 5  means value indicated above. In synthesized compound of the formula (I) one residue of R 3 , R 4  and/or X is transformed to other residue R 3 , R 4  and/or X by saponification of ester group and/or acid compound of the formula (I) is converted to its salt by treatment with a base. Pharmaceutical composition comprises at least one compound of the formula (I) by claim 1 and/or one of its physiologically acceptable salts. Strength of inhibitory effect of compound of the formula (I) on PDE V activity exceeds effect the known structural related compounds by 10-1000 times. EFFECT: improved method of synthesis, valuable medicinal and biochemical properties of compounds. 6 cl, 1 tbl, 20 ex
The invention provides immunostimulatory compositions and use of those compounds in the preparation of medicaments for the treatment of disease as well as in vitro uses. In particular, the compositions of the invention include immunostimulatory oligoribonucleotides that incorporate a sequence-dependent immunostimulatory sequence motif. Specific modifications involving phosphate linkages, nucleotide analogs, adducts, and combinations thereof are provided. Compositions of the invention, which optionally can include an antigen, can be used alone or together with other treatments to stimulate or enhance an immune response. Also provided are compositions and methods useful for treating a subject having an infection, a cancer, an allergic condition, asthma, airway remodeling, or immunodeficiency. Immnostimulatory oligoribonucleotides of the invention are believed to stimulate Toll-like receptor 8 (TLR8).
PURPOSE:To obtain a biologically active polypeptide consisting of amino acid sequence of a specific amino acid, having excellent specific activity and stability, broad reaction spectrum and low side effects and useful for anticancer agent, etc. CONSTITUTION:A desired and appointed code of constitutional amino acid of human tumor necrosis factor (TNF) protein is selected and chemically synthesized to provide a human TNF gene (A), which is then is subjected to gene manipulation to give A gene expression type plasmid (B) (e.g. pTNF401A). Then the B plasmid is subjected to treatment by a restriction enzyme to afford a recombinant plasmid (e.g. pTN473) (C) containing DNA domain coding a biologically (antitumor) active polypeptide having amino sequence such as amino acid, etc., expressed by the formula or the polypeptide whose amino end is combined by Met. Then transformed cell obtained by introducing C plasmid into Escherichia coli, etc., is aerobically cultivated in a culture medium containing glucose, etc., at about 37 deg.C for 2-36hr and a biologically active polypeptide produced and accumulated in the culture medium is isolated.
BACKGROUND: Atrial Fibrillation (AF), a prevalent arrhythmic condition, is intricately associated with atrial fibrosis, a major pathological contributor. Central to the development of atrial fibrosis is myocardial inflammation. This study focuses on Atrial Natriuretic Peptide (ANP) and its role in mitigating atrial fibrosis, aiming to elucidate the specific mechanisms by which ANP exerts its effects, with an emphasis on fibroblast dynamics.
METHODS AND RESULTS: The study involved forty Sprague-Dawley rats, divided into four groups: control, Angiotensin II (Ang II), Ang II + ANP, and ANP only. The administration of 1 µg/kg/min Ang II was given to Ang II and Ang II + ANP groups, while both Ang II + ANP and ANP groups received 0.1 µg/kg/min ANP intravenously for a duration of 14 days. Cardiac fibroblasts were used for in vitro validation of the proposed mechanisms. The study observed that rats in the Ang II and Ang II + ANP groups showed an increase in blood pressure and a decrease in body weight, more pronounced in the Ang II group. Diastolic dysfunction, a characteristic of the Ang II group, was alleviated by ANP. Additionally, ANP significantly reduced Ang II-induced atrial fibrosis, myofibroblast proliferation, collagen overexpression, macrophage infiltration, and the elevated expression of Interleukin 6 (IL-6) and Tenascin-C (TN-C). Transcriptomic sequencing indicated enhanced PI3K/Akt signaling in the Ang II group. Furthermore, in vitro studies showed that ANP, along with the PI3K inhibitor LY294002, effectively reduced PI3K/Akt pathway activation and the expression of TN-C, collagen-I, and collagen-III, which were induced by Ang II.
CONCLUSIONS: The study demonstrates ANP's potential in inhibiting myocardial inflammation and reducing atrial fibrosis. Notably, ANP's effect in countering atrial fibrosis seems to be mediated through the suppression of the Ang II-induced PI3K/Akt-Tenascin-C signaling pathway. These insights enhance our understanding of AF pathogenesis and position ANP as a potential therapeutic agent for treating atrial fibrosis.