anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Mechanism of Action

Stavudine, a nucleoside analogue of thymidine, is phosphorylated by cellular kinases to the active metabolite stavudine triphosphate. Stavudine triphosphate inhibits the activity of HIV-1 reverse transcriptase (RT) by competing with the natural substrate thymidine triphosphate (Ki=0.0083 to 0.032 μM) and by causing DNA chain termination following its incorporation into viral DNA. Stavudine triphosphate inhibits cellular DNA polymerases β and γ and markedly reduces the synthesis of mitochondrial DNA.

Antiviral Activity in Cell Culture

The cell culture antiviral activity of stavudine was measured in peripheral blood mononuclear cells, monocytic cells, and lymphoblastoid cell lines. The concentration of drug necessary to inhibit HIV-1 replication by 50% (EC50) ranged from 0.009 to 4 μM against laboratory and clinical isolates of HIV-1. In cell culture, stavudine exhibited antagonistic activity in combination with zidovudine. The anti-HIV-1 activity of stavudine in combination with either abacavir, didanosine, tenofovir, or zalcitabine was not antagonistic. Ribavirin, at the 9–45 μM concentrations tested, reduced the anti-HIV-1 activity of stavudine by 2.5- to 5-fold. The relationship between cell culture susceptibility of HIV-1 to stavudine and the inhibition of HIV-1 replication in humans has not been established.

Resistance

HIV-1 isolates with reduced susceptibility to stavudine have been selected in cell culture (strain-specific) and were also obtained from patients treated with stavudine. Phenotypic analysis of HIV-1 isolates from 61 patients receiving prolonged (6–29 months) stavudine monotherapy showed that post-therapy isolates from four patients exhibited EC50 values more than 4-fold (range 7- to 16-fold) higher than the average pretreatment susceptibility of baseline isolates. Of these, HIV-1 isolates from one patient contained the zidovudine-resistance-associated substitutions T215Y and K219E, and isolates from another patient contained the multiple-nucleoside-resistance-associated substitution Q151M. Mutations in the RT gene of HIV-1 isolates from the other two patients were not detected. The genetic basis for stavudine susceptibility changes has not been identified.

Cross-resistance

Cross-resistance among HIV-1 reverse transcriptase inhibitors has been observed. Several studies have demonstrated that prolonged stavudine treatment can select and/or maintain thymidine analogue mutation (TAMs) substitutions in the HIV-1 RT (M41L, D67N, K70R, L210W, T215Y/F, K219Q/E) associated with zidovudine resistance. HIV-1 isolates with one or more TAMs substitutions exhibited reduced susceptibility to stavudine in cell culture. These TAMs substitutions are seen at a similar frequency with stavudine and zidovudine in virological treatment. The clinical relevance of these findings suggests that stavudine should be avoided in the presence of thymidine analogue mutation substitutions.
The present invention provides polypeptide with CD56 molecular specificity in conjunction with and its application, the polypeptide selected from least one of No. 7 polypeptides, No. 8 polypeptides, No. 7 polypeptides, No. 8 polypeptides amino acid sequence respectively as shown in sequence 1 in sequence table, sequence 2.Polypeptide provided by the invention can manually synthesize in conjunction with CD56 molecular specificity or the method for genetic engineering produces.Compared with antibody, polypeptide provided by the invention has easily prepared, and molecular weight is small, the features such as being not likely to produce immunological rejection；And toxic side effect is small, and the combination of CD56+ cell, to target cell without the effect of significantly killing and Inhibit proliferaton.Polypeptide provided by the invention is used as the marker of CD56 positive expression cell, also can be used as the sub etc. of immunofluorescence CD56 antibody.
Under-five children's diarrhea is a significant public health threat and the World Health Organization (WHO) reported it as the second leading cause of children's death worldwide. In this study area, little is known about the spatiotemporal distribution of under-5 diarrhea incidence. This study was therefore, conducted among all districts in the Central Gondar zone to assess the spatial, temporal, and spatiotemporal variation in diarrhea incidence among under-five children in the Central Gondar zone. The data for children under 5 years of age with diarrhea was obtained from Central Gondar Zone Health Department diarrhea reports from January 2019 to December 2022. All districts were included and geo-coded. The spatial data were created in ArcGIS 10.8.1. Global and local spatial autocorrelation were used to detect hot spots and cold spots. The Poisson model was generated by applying the Kulldorff method in SaTScan™9.6 to analyse the the purely temporal, spatial, and space-time clusters. The study revealed spatial variation of under-5 diarrhea where Gondar City, Gondar Zuria, East Dembia, and Lay Armacho districts were the high-rate spatial clusters during the study period. A year search window for temporal scan statistic identified 01 January 2020-30 December 2021 as risk periods across all districts. Spatiotemporal scan statistics detected high-rate clusters at Gondar City, Gondar Zuria, East Dembia, Lay Armacho, and Alefa between 2019 and 2022. In conclusion, there has been a spatial, temporal, and spatiotemporal variability of under-5 children's diarrhea in the Central Gondar Zone. Interventional and preventive strategies should be developed and given priority to the areas that has been detected as a hotspot in this study to reduce the mortality and morbidity of under 5 children.
This product may impair mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. Such tasks should be avoided while taking this product.

Alcohol and other CNS depressants may produce an additive CNS depression, when taken with this combination product, and should be avoided.

Butalbital may be habit-forming. Patients should take the drug only for as long as it is prescribed, in the amounts prescribed, and no more frequently than prescribed.

For information on use in geriatric patients, see PRECAUTIONS/Geriatric Use.
* SANDOSTATIN LAR DEPOT should be administered by a trained healthcare provider. It is important to closely follow the mixing instructions included in the packaging. SANDOSTATIN LAR DEPOT must be administered immediately after mixing. 
  * Do not directly inject diluent without preparing suspension.
  * The recommended needle size for administration of SANDOSTATIN LAR DEPOT is the 1½” 19 gauge safety injection needle (supplied in the drug product kit). For patients with a greater skin to muscle depth, a size 2” 19 gauge needle (not supplied) may be used. 
  * SANDOSTATIN LAR DEPOT should be administered intramuscularly (IM) in the gluteal region at 4-week intervals. Administration of SANDOSTATIN LAR DEPOT at intervals greater than 4 weeks is not recommended. 
  * Injection sites should be rotated in a systematic manner to avoid irritation. Deltoid injections should be avoided due to significant discomfort at the injection site when given in that area. 
  * SANDOSTATIN LAR DEPOT should never be administered intravenously or subcutaneously.



The following dosage regimens are recommended.
The purpose of the study is to better understand the mechanism of action of an FDA approved drug (alefacept). Subjects enrolled will be given alefacept 7.5 mg intravenously on a weekly basis for 12 weeks. Response is assessed by improvement in the PASI score. The responders will get no further treatment and the nonresponders will receive additional 4 weeks of therapy. Skin biopsies will be obtained throughout the study and T-cell apoptosis will be correlated to clinical response. There is no placebo group. The duration of the study is approximately 1 year.
A process for the preparation of 3-heteryl-2H-chromen-2-imines and their 2-N-arylimino derivatives by interaction of anthranylamides, or thioanthranylamides, or 2-aminothiophene-3-carboxamides, or thiosemicarbazides with an equimolar amount of 2-amino-2H-chromenes in acetic acid or dimethylformamide while heating. According to the utility model, the 2-amino-2H-chromene-3-carbonitriles or 2-amino-2H-chromene-3-carbothioamides are subjected to the reaction for 20-30 minutes at a temperature of 25-80 ° C with formation of precipitate with the following washing of the filtered precipitate with ethanol or isopropyl alcohol and drying the produced material by heating at a temperature of 135-150 ° Cfor 15 minutes to 3 hours in a dimethylformamide medium with the formation of precipitate which is filtered, washed with ethanol or isopropyl alcohol and dried. The relevant 3-heteryl-2H-chromen-2-imine is prepared, which is added to arylamine solution in equimolar amount. The reaction is conducted at a temperature of 60-80 ° C for 20-30 minutes in glacial acetic acid medium with the following cooling of the reaction mixture to room temperature. Then the precipitate formed is filtered, washed by ethanol or isopropyl alcohol, dried and crystallized from dimethylformamide. Corresponding 2-N-arilimino derivate of 3-heteryl-2H-chromen-2-imine is prepared.
Patients undergo scrambler therapy over 30-45 minutes QD Monday-Friday for 2 weeks. Patients also undergo a quantitative sensory test and a gait assessment test using a FitBit before receiving scrambler therapy, at the end of the first and second weeks of scrambler therapy, and 1 month after the last day of scrambler therapy.
The invention provides a traditional Chinese medicine composition for treating infertility and a method thereof. The Chinese medicinal composition has effects of eliminating dampness, activating qi-flowing, dispersing stagnated liver qi, activating spleen, warming middle warmer, invigorating kidney, removing blood stasis, dredging channels, tonifying kidney, stopping nocturnal emission, tranquilizing, and consolidating fetus. After female takes the medicine, the medicine can tonify kidney qi, nourish essence and blood, nourish thoroughfare and conception vessels and regulate menstruation; after being taken by men, the Chinese medicinal composition can tonify kidney, arrest spontaneous emission, promote blood circulation to remove blood stasis, resolve phlegm, dredge collaterals, clear heat and promote diuresis; thus, the purpose of conception can be achieved. In addition, the traditional Chinese medicine composition is suitable for treating infertility caused by phlegm-dampness, spleen deficiency and liver depression, infertility caused by deficiency of kidney-qi, deficiency of yin and irregular menstruation and infertility caused by obesity polycystic ovary syndrome. When the traditional Chinese medicine composition is taken, after honeyed into pills, the traditional Chinese medicine composition is taken for five minutes twice a day in the morning and evening; the medicine is taken by both men and women simultaneously, and wine is forbidden for one month after taking. The traditional Chinese medicine composition provided by the invention can effectively treat infertility and has high cure rate.
The recommended dose of pregabalin capsules for fibromyalgia is 300 to 450 mg/day. Begin dosing at 75 mg two times a day (150 mg/day). The dose may be increased to 150 mg two times a day (300 mg/day) within 1 week based on efficacy and tolerability. Patients who do not experience sufficient benefit with 300 mg/day may be further increased to 225 mg two times a day (450 mg/day). Although pregabalin was also studied at 600 mg/day, there is no evidence that this dose confers additional benefit and this dose was less well tolerated. In view of the dose-dependent adverse reactions, treatment with doses above 450 mg/day is not recommended [see Adverse Reactions (6.1)].
This is a multi- center, randomized, open-label, Active-controlled phase 3 trial in participants aged 18 to 70 years with chronic liver disease. It is designed to assess the safety, tolerability and efficacy of both 4 ml SC and 10ml IV LAENNEC when administered twice of week for 6 weeks. A total of 226 participants will be randomised to received 4ml SC or 10ml IV of LAENNEC a 1:1 ratio. And in 4 ml SC and 10 ml IV, the ratio of ALD and NAFLD is 1:3. The investigational product will be administered SC or IV twice of week for a duration of 6 weeks. Participants will return to the clinic for follow-up safety and efficacy assessments on weeks 2, 4, 6.
Temporomandibular disorders (TMDs) are the second most common form of orofacial pain after an odontogenic source. Despite their complex aetiopathology they are considered a musculoskeletal disorder. They can have a significant impact on the quality of life of those suffering from TMDs, but can be treated and managed through a mixture of conservative and surgical approaches. Physiotherapists specialising in musculoskeletal therapy and pain management can offer a variety of techniques to help in the treatment and management of TMDs. In this narrative review the evolution of physiotherapy practice in the United Kingdom will be outlined, along with a discussion about physiotherapeutic theoretical frameworks in the management of musculoskeletal disorders and idiopathic TMDs. Finally, a narrative review will be presented, outlining the literature exploring the use of physiotherapy post TMJ surgery, underpinned by a systematic literature search on the topic. After screening for inclusion in the narrative review, eight articles were included for narrative synthesis. The main findings were that there is a relative paucity of studies looking at the value of physiotherapy post TMJ surgery compared with the treatment of idiopathic TMDs, and there is heterogeneity in the physiotherapy programmes described in the literature, but the addition of physiotherapy post TMJ surgery seems to augment the patient's response to surgery. The article concludes by describing the domestic challenges and opportunities of integrating physiotherapy into TMD management pathways.
<P>PROBLEM TO BE SOLVED: To provide novel synthetic approaches for preparing tetracycline analogs.  <P>SOLUTION: The tetracycline class of antibiotics has played a major role in the treatment of infectious diseases for the past 50 years. However, the increased use of the tetracyclines in human and veterinary medicine has led to resistance among many organisms previously susceptible to tetracycline antibiotics. The modular synthesis of tetracyclines and tetracycline analogs described provides an efficient and enantioselective route to a variety of tetracycline analogs and polycyclines previously inaccessible via earlier tetracycline syntheses and semi-synthetic methods. These analogs may be used as anti-microbial agents or anti-proliferative agents in the treatment of diseases of humans or other animals.  <P>COPYRIGHT: (C)2011,JPO&INPIT
This study is a prospective observational multi-centre study. The main objective is assessing the pharmacokinetics (PK) and pharmacodynamics (PD) correlation of clopidogrel action in older adults, i.e. correlation between clopidogrel active metabolite concentration (PK) and platelet response phenotype (PD). The primary outcome is the correlation between the concentration of active metabolite of clopidogrel (PK) over the percentage of maximum aggregation at 10 μM ADP (PD) as a function of age. Inclusion criteria are: age 50-100 years old, hospitalization in one of the 4 participating centres, treatment with clopidogrel 75 milligrammes per day, for at least 10 days. The statistical analysis is a multiple linear regression model with the introduction of an interaction term. The first variable of interest (explanatory) is the concentration of the metabolite. A linear regression model will be used to estimate the proportion of variance explained. The analyses will be conducted with SAS version 9.4 (SAS Institute Inc., Cary, N.C., USA). Results will be published in an international scientific review.
Patients are undergo an antagonist protocol for in-vitro fertilisation and are stimulated with recombinant gonadotropins. When the patient has an estradiol value of 600 ng/L or more and when the patient has at least 6 follicles of 12 mm, the administration of gonadotropins is stopped and replaced by low dose human chorionic gonadotropins.
Every second person with psychosocial problems was randomized into this arm. The intervention consisted of personalized, intensive psychosocial treatment provided by a medical social worker on the basis of the patient's problems for up to 2 years after inclusion.
ETHNOPHARMACOLOGICAL RELEVANCE: The clinical usage of doxorubicin (DOX) is greatly constrained because of its side effects, especially cardiotoxicity. Studies have suggested that ferroptosis of cardiomyocytes is one of the important causes of doxorubicin-induced cardiotoxicity (DIC). Up-regulating Nuclear erythroid factor 2-related factor 2 (Nrf2) is a potential way to prevent ferroptosis associated with DIC. Qishen granules (QSG) has been shown cardioprotective effects on various cardiovascular diseases, including DIC. However, the mechanism of QSG to prevent and treat DIC are not fully understood.
AIM OF THE STUDY: The main purpose of this work is to probe whether QSG can mitigate DIC by inhibiting ferroptosis, and whether QSG suppresses ferroptosis via Nrf2 pathway.
MATERIALS AND METHODS: The effects of QSG on mitigating DIC and the potential targets of QSG were investigated in a DIC mice model. The cardiac function of mice was monitored by echocardiography. Transmission electron microscopy was used to assess mitochondrial damage. ROS content was measured by dihydroethidium (DHE) staining. The glutathione (GSH) and malondialdehyde (MDA) levels in cardiac tissue were detected by kits to evaluate cellular oxidative stress. The accumulation and nuclear translocation of Nrf2 was detected by immuno-fluorescence. Ferroptosis analysis was determined by tissue iron content and key proteins in Nrf2 pathway were measured by western blotting. The anti-oxidant and anti-ferroptosis mechanisms of QSG were explored in vitro studies. Delivery of Nrf2 small interfering RNA (siRNA) to H9c2 cells aimed to investigate whether QSG could prevent DIC through Nrf2 signaling pathway. The protective effects of QSG on mito-chondrial function and free iron were measured by MitoSOX™ Red and FerroOrange staining assays, respectively.
RESULTS: In vivo, QSG could improve heart function and suppress ferroptosis in DIC mice. DOX-induced ROS production decreased after QSG treatment. The accumulation of free iron and MDA induced by DOX was suppressed with QSG treatment. The level of GSH increased after QSG intervention. QSG also protected against DOX-induced mitochondrial structural damage. Meanwhile, QSG promoted the expression of Nrf2 pathway-related proteins, thereby resisting ferroptosis. In vitro, QSG exerted anti-oxidant and anti-ferroptosis effects. QSG promoted the nuclear-translocation of Nrf2. In addition, interference with Nrf2 attenuated the regulatory effect of QSG on free iron content and mitochondrial ROS production. Moreover, Nrf2 knockdown weakened the anti-ferroptosis effects of QSG and inhibited the expressions of key proteins in Nrf2 pathway.
CONCLUSION: The results of this study first illustrated that QSG could alleviate DIC by suppressing ferroptosis via Nrf2 pathway. Nrf2 may be a potential key target for QSG to prevent and treat DIC.
PURPOSE:To obtain a new compound having a citotoxicity against a tumor cell and an inhibiting activity against protease and useful as an antitumor agent and as a treating agent for muscular dystrophy, cardial infarction, osteoporosis, fulminant hepatic failure, cataract, etc. CONSTITUTION:A compound of formula I (ring Cn is C cluster, one of whose double bonds is replaced by single bond; A is 1-5C alkylene; B is 1-10C alkylene). The compound is obtained by reacting a hydroxy derivative of a C cluster of formula II with a cyclic anhydride of formula III in the presence of an amine, e.g. 4-dimethylaminopyridine in a solvent, e.g. methylene chloride. A medicine containing a compound of formula I is orally administered in a daily dose of 0.01-1000 mg and is administered in a single dose of 0.001-100 mg for adult in an injection. This compound is also useful as a treating agent for Alzheimer's disease, cerebral apoplexy, pancreatitis, etc.
The study plans to enroll 148 patients with heterozygous familial hypercholesterolemia. Subjects will maintain a low-fat diet and stable current lipid-lowering therapy for at least 4 weeks and will be randomized into different dose groups at a 1:1 ratio, followed by a 2:1 randomization double-blind treatment with subcutaneous IBI306 150 mg (n=49) or placebo (n=25) every two weeks; or subcutaneous injection of IBI306 450mg (n=49) or placebo (n=25) every four weeks. Treatment lasts for 12 weeks. After 12 weeks, each group enters a 12-week open-label treatment, in which IBI306 subjects continue to receive IBI306, and placebo subjects shift to receive IBI306. The primary endpoint is the percent change in LDL-C levels relative to baseline at 12 weeks. Secondary endpoints include changes in baseline lipid levels, drug safety, and immunogenicity at 12 weeks and 24 weeks. The exploratory endpoint is the population pharmacokinetic profile of IBI306 in Chinese subjects with heterozygous familial hypercholesterolemia. If necessary, the dose of IBI306 will be adjusted accordingly based on the results of the ongoing multi-dose escalation study. After the open period, the subjects will be given a safety visit for 8 weeks.
Systems, apparatuses, and methods provide for matching unassigned patient data to individual patients. For example, such operations include collecting data from a plurality of data sources in a plurality of formats. Data time stamps are converted from collected data to universal time zone data time stamps. A same patient is matched to the collected data based on the universal time zone data time stamp. A quality estimate of the match is quantified. The match and quality estimate of the match are transferred to a user interface.
Infertile male patients will receive the antioxidant formula for more than 172 days. Divided in two groups. One will take the active substance, to the other group placebo treatment will be given.
Participants in the intervention group will complete a 4-week school-based high-intensity interval exercise training programme. The intervention will take place twice per week, and comprise of 6-8 repetitions of 45 s maximal effort exercise (boxing, running, soccer and basketball drills), each interspersed with 90-s rest. Participants will be encouraged to work maximally during the 45-s repetitions.
PURPOSE:To refine easily and quickly the protein specific to the rheumatism having extremely high purity by using the protein A derived from an antihuman IgG antibody or staphylococcus. CONSTITUTION:The raw material of rheumatism patient's plasma or the like is subjected to electrophoresis with polyacrylamide as a support and the fraction corresponding to the position is recovered. The protein component is then extracted from the fraction recovered by a soln. such as, for example, a phosphoric acid buffer soln. The protein A derived from, for example, antihuman antibody or staphylococcus is separately conjugated such a gel as cephalose 4B by a ligand such as cyanogen bromide. The protein specific to the rheumatism roughly refined by an ion exchange chromatography is passed through such gel. The protein specific to the rheumatism is separated from the affinity gel by a method for removing the non-conjugated component of the affinity gel, then changing the pH by a glycine buffer soln. etc. Such protein is recovered and the protein specific to the rheumatism is refined.