anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The safety and effectiveness of Mirena was studied in two clinical trials in Finland and Sweden. In these trials, 1,169 women 18 to 35 years of age at enrollment used Mirena for up to 5 years, for a total of 45,000 women-months of exposure. Of these, 5.6% (66) were nulliparous women. Subjects had previously been pregnant, had no history of ectopic pregnancy, had no history of pelvic inflammatory disease over the preceding 12 months, were predominantly White, and over 70% of the subjects had previously used IUDs (intrauterine devices). The reported 12-month pregnancy rates were less than or equal to 0.2 per 100 women (0.2%) and the cumulative 5-year pregnancy rate was approximately 0.7 per 100 women (0.7%). 

The contraceptive efficacy of Mirena during extended use beyond 5 years was studied in the Mirena Extension Trial (NCT02985541), a multi-center, open-label, uncontrolled study conducted in the United States. The trial enrolled women 18 to 35 years of age who had been using Mirena for not less than 4.5 years and not more than 5 years at enrollment. The population consisted of 362 women using Mirena. Of these 47.2% were nulliparous. The women were predominantly White (75.4%); 14.1% of the women were Black/African American, and 2.5% were Asian; 11.3 % were Hispanic. The weight range was 38.5–163.5 kg (mean weight: 75.6 kg) and mean BMI was 27.9 kg/m2 (range: 15.4–57.7 kg/m2). 

The pregnancy rate calculated as the Pearl Index (PI) was the primary efficacy endpoint used to assess contraceptive efficacy. The PI was based on 28-day equivalent exposure cycles; evaluable cycles excluded those in which back-up contraception was used unless a pregnancy occurred in that cycle. The PI for the 6th year of use based on the 1 pregnancy that occurred during Year 6 and within 7 days after Mirena removal or expulsion and 3,870 evaluable cycles was 0.34 with a 95% upper confidence limit of 1.88, and the PI for the 7th year of use based on the 1 pregnancy that occurred during Year 7 and within 7 days after Mirena removal or expulsion and 3,232 evaluable cycles was 0.40 with a 95% upper confidence limit of 2.25. The PI for the 8th year of use based on no pregnancies occurring during Year 8 and within 7 days after Mirena removal or expulsion and 2,534 evaluable cycles was 0.00 with a 95% upper confidence limit of 1.90.

The cumulative 3-year pregnancy rate for Years 6, 7 and 8 was estimated by the Kaplan-Meier method. Based on 2 pregnancies (1 in Year 6 and 1 in Year 7) and 10,216 exposure cycles, the cumulative pregnancy rate at the end of the 3-year period of extended use (Years 6, 7 and 8) was 0.68% with a 95% upper confidence limit of 2.71%.
FIELD: organic chemistry, chemical technology, pharmacy. SUBSTANCE: invention relates to the use of 2-phenyl-2-methylaminoethoxy-1,7,7-trimethylbicyclo[2,2,1] -heptane of the formula (I)  , its optically active isomers and pharmaceutically acceptable salts that are able for selective binding with 5-HT 2C -receptors in pharmaceutical compositions eliciting anxiolytic effect. Indicated compounds are synthesized by demethylation of compound of the formula (II)   by reaction with Hlg-COOR 1  where Hlg means halogen atom; R 1  means alkyl to yield compound of the formula (V)   that is treated with a base or by removal of protective group R from compound of the formula (III)   and if necessary by separation of obtained racemate for optical isomers and/or by conversion to pharmaceutically acceptable salt or a base is isolated from salt. Pharmaceutical composition comprises above indicated compounds with suitable inert solid or liquid filling agents or accessory agents. Composition is prepared by mixing indicated components and if necessary the prepared form is converted to form useful for application. EFFECT: improved method of synthesis and preparing, valuable medicinal properties of compounds. 15 cl, 4 tbl, 6 ex
AIMS: Silicosis is the most common and severe type of pneumoconiosis, imposing a substantial disease burden and economic loss on patients and society. The pathogenesis and key targets of silicosis are not yet clear, and there are currently no effective treatments available. Therefore, we conducted research on mefunidone (MFD), a novel antifibrotic drug, to explore its efficacy and mechanism of action in murine silicosis.
METHODS: Acute 7-day and chronic 28-day silicosis models were constructed in C57BL/6J mice by the intratracheal instillation of silica and subsequently treated with MFD to assess its therapeutic potential. The effects of MFD on silica-induced inflammation, pyroptosis, and fibrosis were further investigated using immortalized mouse bone marrow-derived macrophages (iBMDMs).
RESULTS: In the 7-day silica-exposed mouse models, MFD treatment significantly alleviated pulmonary inflammation and notably reduced macrophage infiltration into the lung tissue. RNA-sequencing analysis of silica-induced iBMDMs followed by gene set enrichment analysis revealed that MFD profoundly influenced cytokine-cytokine receptor interactions, chemokine signaling, and the toll-like receptor signaling pathways. MFD treatment also markedly reduced the secretion of inflammatory cytokines and chemokines from silica-exposed iBMDMs. Moreover, MFD effectively downregulated the activation of the TLR4-NF-κB/MAPK signaling pathway induced by silica and mitigated the upregulation of pyroptosis markers. Additionally, MFD treatment significantly suppressed the activation of fibroblasts and alveolar epithelial cells co-cultured with silica-exposed mouse macrophages. Ultimately, in the 28-day silica-exposed mouse models, MFD administration led to a substantial reduction in the severity of pulmonary fibrosis.
CONCLUSION: MFD mitigates silica-induced pulmonary inflammation and fibrosis in mice by suppressing the TLR4-NF-κB/MAPK signaling pathway and reducing pyroptotic responses in macrophages. MFD could potentially emerge as a novel therapeutic agent for the treatment of silicosis.
Hepatoblastoma is the most common primary liver cancer in children. Poor outcomes are primarily associated with patients who have distant metastases. Using the Mammalian Metabolic Enzyme Database, we investigated the overexpression of metabolic enzymes in hepatoblastoma tumors compared to noncancerous liver tissue in the GSE131329 transcriptome dataset. For the overexpressed enzymes, we applied ElasticNet machine learning to assess their predictive value for metastasis. A metabolic expression score was then computed from the significant enzymes and integrated into a clinical-biological logistic regression model. Forty-one overexpressed enzymes distinguished hepatoblastoma tumors from noncancerous liver tissues. Eighteen of these enzymes predicted metastasis status with an AUC of 0.90, demonstrating 85.7% sensitivity and 92.3% specificity. ElasticNet machine learning identified DNMT3B and PFKFB4 as key predictors of metastasis. Univariate analyses confirmed the significance of these enzymes, with respective p-values of 0.0058 and 0.0091. A metabolic score based on DNMT3B and PFKFB4 expression discriminated metastasis status and high-risk CHIC scores (p-value = 0.005). The metabolic score was more sensitive than the C1/C2 classifier in predicting metastasis (accuracy: 0.72 vs. 0.55). In a regression model integrating the metabolic score with epidemiological parameters (gender, age at diagnosis, histological type, and clinical PRETEXT stage), the metabolic score was confirmed as an independent adverse predictor of metastasis (p-value = 0.003, odds ratio: 2.12). This study identified the dual overexpression of PFKFB4 and DNMT3B in hepatoblastoma patients at risk of metastasis (high-risk CHIC classification). The combined tumor expression of DNMT3B and PFKFB4 was used to compute a metabolic score, which was validated as an independent predictor of metastatic status in hepatoblastoma.
The intervention program is a person-centered health promotion program led by a nurse and consists of two telephone calls (15 minutes each) at two weeks and nine months after surgical treatment for Intermittent Claudication and three visits (45 - 60 min) at six weeks, six months and one year after treatment. The program includes a baseline assessment, an individual plan for self-care and educational information about Intermittent Claudication, received treatment and secondary prevention (medication and modifiable risk factors). The purpose is to enhance self-care in terms of adherence to medication and to recommended changes of lifestyle.
Negative symptoms are one of the five-dimensional symptoms of patients with schizophrenia. Drug treatment of negative symptoms is not effective. Even if the positive symptoms are relieved, the negative symptoms continue to exist, which seriously affects the personal family social function and is an important risk factor for poor prognosis. The mechanism of negative symptoms of schizophrenia is unknown, which may be related to insufficient dopamine function of the prefrontal cortex, but the pathogenesis is still not fully explained. Amisulpride is a D2/D3 receptor antagonist, which can improve negative symptoms, but the mechanism is not clear. Intestinal microbes are related to central nervous system psychiatric diseases, and intestinal flora imbalance may be an important cause of autism, anxiety, depression, schizophrenia and other mental and psychological diseases. Under pathological conditions, when the intestinal microbiome is disturbed or the intestinal mucosal barrier is destroyed, microbial-related molecules stimulate macrophages and dendritic cells to produce pro-inflammatory cytokines, which in turn activate adaptive immune cells, leading to the destruction of immune homeostasis and enteric nerves The system can also interact with the central nervous system through the brain-gut axis. Intestinal microbes may also influence the occurrence of mental illness through metabolites. Animal studies have found that changes in the intestinal microflora are related to schizophrenia. Clinical studies have found that the gut microbes of patients with schizophrenia are different from those of normal healthy people. Therefore, we are trying to discover the changes of gut microbes in patients with effective amisulpride treatment, and to improve the negative symptoms of schizophrenia patients through the intestinal immune system. The mechanism of brain relationship provides direction, and also provides a new way for the drug treatment of negative symptoms. This study intends to select 30 patients with schizophrenia with dominant negative symptoms (study group) and 15 healthy people with similar living environment (control group), and the study group will be treated with amisulpride (flexible treatment), negative symptom factor The score reduction rate reached 20% for the effective group. Followed up for 8 weeks, fresh stool samples were collected at the baseline, 2, 4, and 8 weekends for 16S rRNA sequencing and short-chain fatty acid detection, and whole blood samples for immune factors (IL-1β, IL-6, IL-10, TNF) -α) Test to assess the negative symptom factor scores of PANSS, CDSS, CGI, TESS, SAS, and Barnes akathisia, and evaluate the patient's negative symptoms, depressive symptoms, efficacy and adverse reactions in turn. Comparing the differences in the intestinal microflora of the two groups at baseline, the correlation between the changes of the intestinal microflora of the effective group of amisulpride and the immune factors and negative symptoms. To understand the pathogenesis of schizophrenia patients with dominant negative symptoms through the gut microbiota-brain axis.
The use of complementary and alternative medicine (CAM) has grown dramatically over the last decade. Botanical treatments originating from plants have become especially popular for treating conditions such as anxiety and depression. Evidence suggests that the botanical St. John's wort has neurochemical activity similar to that of conventional medications. However, research on the safety and effectiveness of St. John's wort is limited. This study will determine the safety and effectiveness of St. John's wort in treating GSAD, a serious condition characterized by intense fear of various social situations that may cause embarrassment.

Participants will be randomly assigned to receive either St. John's wort or placebo daily for 10 weeks. Self-report scales will be used to assess participants' GSAD symptoms at study entry and at study completion. Blood collection will occur at every weekly study visit to determine the levels of St. John's wort in the blood.
PURPOSE: A glycol chitosan derivative is provided to have improved solubility to organic solvent, to form nanosized self aggregate, and to have thermo-sensitive sol/gel phase transition behavior, thereby using for drug delivery system. CONSTITUTION: A glycol chitosan derivative has a structure of chemical formula 1. In chemical formula 1, n is the integer of 10-10000. The acetylation degree of the glycol chitosan derivative is 20-90%. A manufacturing method of the glycol chitosan derivative in chemical formula 1 comprises a step of acetylation of glycol chitosan in chemical formula 1 to an acetylating agent. The acetylating agent is acetic anhydride. The drug delivery system comprises the chitosan derivative.
PURPOSE: A method for suppressing cell death by inhibition of AGE-albumin synthesis or secretion in a mononuclear phagocyte system is provided to diagnose or treat degenerative diseases and autoimmune diseases. CONSTITUTION: A method for suppressing cell death comprises a step of inhibiting synthesis or secretion of AGE(advanced glycation end-product)-albumin in a mononuclear phagocyte system. Cell death-induced cells are adjacent to the mononuclear phagocyte system. The cells are nerve cells, chondrocytes, lung cells, or liver cells. The cells of the mononuclear phagocyte system is microglia of brain, blood mononuclear cells, alveolar macrophage(type II pneumocyte, dust cell), Langehans cells of skin, or macrophage. A pharmaceutical composition for preventing or treating degenerative diseases and auto-immune diseases contains an inhibitor of AGE-albumin synthesis as an active ingredient.
In Arm A, S-1 25 mg/m² was administered orally BID from Day 1 through Day 21 followed by a recovery period from Days 22 through Day 28. On Day 1, the morning dose of S-1 was administered before cisplatin 75 mg/m2 administration as a 1- to 3-hour IV infusion. This regimen was repeated every 4 weeks. S-1 was administered one hour before or one hour after a meal with a glass of water (approximately 100 mL).
PURPOSE:To obtain an immunosuppressant containing a forskolin derivative as an active ingredient and applicable to suppression of refuse reaction in organ transplantation or skin transplantation. CONSTITUTION:This immunosuppressant contains 6-(3-dimethyl-aminopropionyl) forskolin expressed by the formula or its salt as an active ingredient. The agent is as necessary blended with an excipient, a carrier, etc., and the blend is prepared in a form of injection, oral agent, suppository, etc. The blend amount of the compound expressed by the formula is 0.1-30wt.% in the case of injection and 5-100wt.% in the case of oral agent. The daily dose of the compound of the formula is 1-100mg/kg in the case of parenteral administration and 5-500mg/kg in the case of oral administration. Life of transplanted organs or skin can be prolonged by daily dose of 1-3mg/kg, compared with non- administration group, and the agent has immunosuppressing action and is useful also for treatment of autoimmune disease.
Interferential current (IFC) is a medium frequency current derived from the interference of two symmetrical, but asynchronous alternating currents ranged from 1 to 10 KHz. The two main currents resulting in a single interference current with properties uniquely different from the two original currents.The lesser current of the two original currents is termed the carrier frequency and the interference current is called the beat frequency. A specific beat frequency can be obtained from several possible interference currents as long as the difference between the original currents is the same. For electro pain modulation, IFC is commonly used form of electrotherapy. It has the advantage of reducing the skin impedance, deeper penetration into tissues and is perceived as more comfortable.

Myofascial pain syndrome (MPS) is a common form of chronic musculoskeletal pain that widely spread and contributing to a significant financial burden and job- related disability. It represents the most common disorder in patients with nonspecific chronic neck pain.The main characteristics of MPS include the presence of myofascial trigger points (MTrPs) which are defined as hyperirritable nodule in a taut band of skeletal muscle fibers which is palpable and tender during physical examination. Trigger points (TrPs) are usually seen in the upper fiber of trapezius. TrPs can be clinically classified as either active or latent. Active TrPs was defined as: MTrPs that refer pain during activity and during rest without any pressure. They prevent full muscle lengthening and induce their weakness. Latent TrPs was defined as: MTrPs that is painful only when palpated. Evidence on the effect of IFC on pain modulation is not confirmed up till now. This might be attributed to multiple factors such as limited number of studies, inappropriate use of the parameters or using single carrier frequency (4 KHz) in majority of studies and the physiological effects of all our modalities are dose dependent. Dose depends on details of parameters including frequency. For IFC, the carrier frequency of the current has been suggested as an important parameter to achieve the most effective hypoalgesic response. However, there remains no evidence to support the selection of one carrier frequency over another. Few studies were conducted to examine the effect of different carrier frequencies by comparing their individual effects. Further researches are needed to prove which carrier frequency is more effective in treatment. Therefore, this study will be conducted to compare the effect of different carrier frequencies of the IFC in the management of upper trapezius chronic TrPs.
This group will have a regular eye exam with the collection of tears. In addition, a the Ocular Surface Disability Index Survey of National Eye Institute Visual Functioning Questionnaire- 25 may be administered.
According to the bio-informational theory of emotion by Lang, mental imagery of fearful stimuli activates physiological and behavioural response systems, even in the absence of sensory input. We investigated whether instructed mental imagery of pain-associated (not painful) interoceptive sensations entails a threat value and elicits increased startle response, skin conductance level (SCL), and heart rate (HR) indicative of defensive mobilization in adolescents with chronic pain. Additionally, self-reported measures (fear, fear of pain, desire to avoid) were assessed. Adolescents (11-18 years) with chronic headache (CH, n = 46) or chronic abdominal pain (CAP, n = 29) and a control group (n = 28) were asked to imagine individualized pain-associated, neutral and standardized fear scripts. During pain-associated compared with neutral imagery, both pain groups showed higher mean HR, with CH also showing higher HR reactivity, while HR acceleration was not observed within control group. In contrast, during pain-associated compared with neutral imagery, startle response magnitude and SCL remained unchanged in all groups. Additionally, overall levels in self-reports were higher during pain-associated compared with neutral imagery, but significantly more pronounced in the pain groups compared with the control group. Results suggest that the mere imagination of pain-associated sensations elicits specific autonomic fear responses accompanied by increased self-reported fear in adolescents with chronic pain. The specific modulation of heart rate shed new light on our understanding of multimodal fear responses in adolescents with chronic pain and may help to refine paradigms to decrease fear of interoceptive sensations in chronic pain.
Patients will be receive S-1 based chemotherapy, including S-1 plus cisplatin or S-1 alone.Cycles were repeated every 21 days. Treatment was continued until disease progression, unacceptable toxic effects, or the withdrawal of consent.
The present invention relates to a cell surface modification method for modifying a cell surface such as a pancreas islet cell using poly (lactic-co-glycolic acid) microsphere coated with polydopamine. The cell surface modification method has a simple process than that of an existing cell surface modification method. The cell surface modification method can extend discharge of drugs to a periphery of a fine environment of a cell by enabling encapsulation of a large quantity of target drugs. Also, the cell surface modification method can transmit a bioactive substance or various kinds of the drugs such as an immunosuppressant or an anticoagulant agent to obtain multiple effects. Therefore, the cell surface modification method can improve a transplant rate of the cell and can reduce non-specific immune reaction. Therefore, the cell surface modification method can be used as a new cell medicine transmission system.
The present invention generally relates to particles such as nanoparticles and, in particular, to targeted nanoparticles. In some cases, the particles may have a targeting moiety that is inhibited from recognizing a target, for example, by being positioned within the particle at an internal location. The application of a stimulus, such as light, may allow the targeting moiety to interact externally of the particle. Accordingly, the particles may be targeted to specific locations using the application of a suitable stimulus. For instance, in one embodiment, particles containing cell-penetrating peptides attached via a first attachment and a second attachment containing a photocleavable entity may be administered to a subject, and light may be applied, e.g., to the eye, to cleave the photocleavable entity. However, despite the cleavage, the peptides remain associated with the particle via the first attachment, and thus, the particles may be able to penetrate cells within the eye due to peptides. Other aspects are generally directed to methods of making or using such particles, kits involving such particles, or the like.
Methods of permanent shaping and volumizing hair that are gentle and prevent overcurling are described. In one method using curlers to curl the hair, an alkaline permanent shaping composition having a pH of 7.6 to 11 and including a hair keratin-reducing substance is applied to the hair and allowed to act on the hair for 5 to 30 minutes at room temperature or for 2 to 20 minutes at an elevated temperature. Then the hair is optionally rinsed with water and subsequently with an acidic aqueous intermediate rinse, which has a pH of 2 to 6.5 and includes an aliphatic organic acid. Next the hair is wound onto curlers, after which the hair is allowed to rest for 30 minutes at room temperature or 20 minutes at an elevated temperature. After the resting period the hair is treated with an oxidant-based fixative, which can be a solution of hydrogen peroxide, and the curlers are removed. The hair is subsequently rinsed with water or washed with a shampoo to remove the fixative and combed into a hair style. For methods of uncurling hair the method is similar, but the step of winding on curlers is replaced by a step of combing the hair out and the acidic aqueous intermediate treating agent is in the form of a gel, cream or paste.
Patients receive rituximab IV on days 1, 8, 15, and 22. Patients then receive low-dose aldesleukin SC on days 29-39, 43-53, 57-67, and 71-81, and intermediate-dose aldesleukin SC on days 40-42, 54-56, 68-70, and 82-84.