anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
BACKGROUND: Observational studies and randomized controlled trials have found evidence that higher maternal circulating cortisol levels in pregnancy are associated with lower offspring birth weight. However, it is possible that the observational associations are due to residual confounding.
METHODS: We performed two-sample Mendelian Randomisation (MR) using a single genetic variant (rs9989237) associated with morning plasma cortisol (GWAS; sample 1; N = 25,314). The association between this maternal genetic variant and offspring birth weight, adjusted for fetal genotype, was obtained from the published EGG Consortium and UK Biobank meta-analysis (GWAS; sample 2; N = up to 406,063) and a Wald ratio was used to estimate the causal effect. We also performed an alternative analysis using all GWAS reported cortisol variants that takes account of linkage disequilibrium. We also tested the genetic variant's effect on pregnancy cortisol and performed PheWas to search for potential pleiotropic effects.
RESULTS: The estimated effect of maternal circulating cortisol on birth weight was a 50 gram (95% CI, -109 to 10) lower birth weight per 1 SD higher log-transformed maternal circulating cortisol levels, using a single variant. The alternative analysis gave similar results (-33 grams (95% CI, -77 to 11)). The effect of the cortisol variant on pregnancy cortisol was 2-fold weaker than in the original GWAS, and evidence was found of pleiotropy.
CONCLUSIONS: Our findings provide some evidence that higher maternal morning plasma cortisol causes lower birth weight. Identification of more independent genetic instruments for morning plasma cortisol are necessary to explore the potential bias identified.
The safety and effectiveness of FETZIMA have not been established in pediatric patients for the treatment of major depressive disorder (MDD). 

The safety and efficacy of FETZIMA were evaluated in two randomized, double-blind, placebo- and active-controlled 8-week trials in pediatric patients with MDD, one in patients 7 to 17 years of age (flexible-dose study) and the other in patients 12 to 17 years of age (fixed-dose study). The primary efficacy endpoint for both studies was the change from baseline to week 8 in the Children’s Depression Rating Scale-Revised (CDRS-R) total score. The CDRS-R assesses the severity of depression and change in depressive symptoms in children and adolescents with depression. FETZIMA was not superior to placebo in either study. The most commonly observed adverse reactions in pediatric patients 7 to 17 years of age randomized to FETZIMA were similar to those observed in adults [see Adverse Reactions (6.1)].

FETZIMA was associated with an increase in blood pressure in placebo- and active-controlled trials in pediatric patients with MDD. Increases in blood pressure in pediatric patients treated with FETZIMA led to a higher proportion of pediatric patients developing new-onset and sustained hypertension when compared to adults [see Warnings and Precautions (5.3)].

Antidepressants increase the risk of suicidal thoughts and behaviors in pediatric patients [see Boxed Warning, Warnings and Precautions (5.1), and Adverse Reactions (6.1)].

Juvenile Animal Toxicity Data

In a juvenile animal study, male and female rats were treated with 10, 35, or 120 mg/kg/day of levomilnacipran by oral gavage from post-natal day 21 to 90. At 120 mg/kg/day, there was a decrease in bone mineral density in both males and females and a decrease in mean tibia length in females. These effects were not completely resolved at the end of the recovery period. There was a delay in sexual maturation in females treated with 120 mg/kg/day; however, there was no effect on fertility. The no observed adverse effect level (NOAEL) for all these findings was 35 mg/kg/day.
Subjects will have weekly psychotherapy sessions and fill out study questionnaires. The participant's 4th psychotherapy session will be conducted while the patient undergoes the WBH intervention where subjects will be induced to levels of heat that increases core body temperature to approximately 37.5-38.5 °C.temperature.
The project of Guangdong GAMI(reGional network for Acute Myocardial Infarction) is being conducted during 2015-2019 in eight districts with diverse economic development across southern China (Integrated care model was conducted in four regions, which mainly included community public education, non primary-PCI capable centre and referral system improvement, and inhospital green-channal optimization for primary-PCI capable centre. Other four centers were underwent usual care of acute myocardial infacrtion public and medical health service). All the ST-segment elevation myocardial infarction (STEMI) patients admitted in the hospital within 30 days from the symptom onset were enrolled. The key data of the timeline of STEMI onset and treatment were precisely recorded. Other details of STEMI treatment in hospitals such as laboratory data and medication were also collected. During the research period, actions of both optimizing the regional STEMI patients transfer and treatment to shorten the medical delay, as well as educating the public to improve their awareness of early treatment of STEMI were taken meanwhile. In addition, laboratory data, medication, and follow-up information were recorded in a database for further analysis regarding the STEMI patient treatment.
The invention discloses a traditional Chinese medicine pill for invigorating pulse and benefiting heart, which is prepared from the following components in part by weight: the invention relates to a traditional Chinese medicine composition for treating rheumatism, which is prepared from 12 traditional Chinese medicines including ginseng, raw astragalus root, ground beeltle, cassia twig, tuckahoe, raw white atractylodes rhizome, alisma orientale, herba lycopi, prepared rhizome of rehmannia, salvia miltiorrhiza, nardostachys root and rhizome, honey-fried licorice root and the like. 1. Has no influence or little influence on normal physiological functions and no toxic or side effect. 2. The effect is nonspecific and broad-spectrum. 3. Has the functions of regulating the normal physiological function of the heart, promoting blood circulation, producing sperm and nourishing blood, and banking up and nourishing heart, and has good treatment effect on the apoplexy caused by deficiency of both qi and yin and blood stasis. 4. Can effectively improve the symptom sign of a patient with myocardial infarction, benefit qi, tranquilize mind, calm heart, eliminate pathogenic factors and strengthen body resistance.
Mitotic Arrest Deficient 1 (gene name MAD1L1), an essential component of the mitotic spindle assembly checkpoint, is frequently overexpressed in colon cancer, which correlates with poor disease-free survival. MAD1 upregulation induces two phenotypes associated with tumor promotion in tissue culture cells-low rates of chromosomal instability (CIN) and destabilization of the tumor suppressor p53. Using CRISPR/Cas9 gene editing, we generated a novel mouse model by inserting a doxycycline (dox)-inducible promoter and HA tag into the endogenous mouse Mad1l1 gene, enabling inducible expression of HA-MAD1 following exposure to dox in the presence of the reverse tet transactivator (rtTA). A modest 2-fold overexpression of MAD1 in murine colon resulted in decreased p53 expression and increased mitotic defects consistent with CIN. After exposure to the colon-specific inflammatory agent dextran sulfate sodium (DSS), 31% of mice developed colon lesions, including a mucinous adenocarcinoma, while none formed in control animals. Lesion incidence was particularly high in male mice, 57% of which developed at least one hyperplastic polyp, adenoma or adenocarcinoma in the colon. Notably, mice expressing HA-MAD1 also developed lesions in tissues in which DSS is not expected to induce inflammation. These findings demonstrate that MAD1 upregulation is sufficient to promote colon tumorigenesis in the context of inflammation in immune-competent mice.
Persistent no-show rates contribute to the oral health disparities and inadequate access to dental care that disproportionately affect underserved populations. The proposed research will test the impact of three different strategies on improving show rates using a full factorial design. Specifically, the study is designed as a 2×2×2 factorial cluster-randomized trial of reminder messaging, motivation-enhanced communication, and walk-in visit. The unit of intervention and randomization will be dental clinic sites (clusters). Forty clinics will be randomized between eight possible combinations of receiving or not receiving the three study interventions, with five clinics receiving each intervention. Findings from this study seek to provide an evidence-based approach to reducing no-shows and increasing access to dental care for underserved populations.
A method is provided for assigning longitudinal linking tags to de-identified patient data records by matching the patient data records with reference data records. The de-identified patient data records may include both encrypted and non-encrypted data attributes. Different possible subsets of the data attributes are categorized in a hierarchy of levels. Subsets of data field values are compared with the reference data records one level at a time. Upon successful comparison or matching of a subset of data field values, a longitudinal linking tag associated with a matched reference data record is assigned to de-identified data record is assigned. When a match is not found, a new longitudinal linking tag is created and assigned to the de-identified data record. The new tag and corresponding data record attributes are then added to the reference data for future matching operations.
14.1 Chronic Heart Failure   
Two 12-week, double-blind, placebo-controlled studies enrolled 178 (RADIANCE trial) and 88 (PROVED trial) adult patients with NYHA Class II or III heart failure previously treated with oral digoxin, a diuretic, and an ACE inhibitor (RADIANCE only) and randomized them to placebo or treatment with Digoxin Tablets. Both trials demonstrated better preservation of exercise capacity in patients randomized to digoxin. Continued treatment with digoxin reduced the risk of developing worsening heart failure, as evidenced by heart failure-related hospitalizations and emergency care and the need for concomitant heart failure therapy.

DIG Trial of Digoxin in Patients with Heart Failure

The Digitalis Investigation Group (DIG) main trial was a 37-week, multicenter, randomized, double-blind mortality study comparing digoxin to placebo in 6800 adult patients with heart failure and left ventricular ejection fraction less than or equal to 0.45. At randomization, 67% were NYHA class I or II, 71% had heart failure of ischemic etiology, 44% had been receiving digoxin, and most were receiving a concomitant ACE inhibitor (94%) and diuretics (82%). As in the smaller trials described above, patients who had been receiving open-label digoxin were withdrawn from this treatment before randomization. Randomization to digoxin was again associated with a significant reduction in the incidence of hospitalization, whether scored as number of hospitalizations for heart failure (relative risk 75%), risk of having at least one such hospitalization during the trial (RR 72%), or number of hospitalizations for any cause (RR 94%). On the other hand, randomization to digoxin had no apparent effect on mortality (RR 99%, with confidence limits of 91-107%).

14.2 Chronic Atrial Fibrillation   
Digoxin has also been studied as a means of controlling the ventricular response to chronic atrial fibrillation in adults. Digoxin reduced the resting heart rate, but not the heart rate during exercise.

In 3 different randomized, double-blind trials that included a total of 315 adult patients, digoxin was compared to placebo for the conversion of recent-onset atrial fibrillation to sinus rhythm. Conversion was equally likely, and equally rapid, in the digoxin and placebo groups. In a randomized 120-patient trial comparing digoxin, sotalol, and amiodarone, patients randomized to digoxin had the lowest incidence of conversion to sinus rhythm, and the least satisfactory rate control when conversion did not occur.

In at least one study, digoxin was studied as a means of delaying reversion to atrial fibrillation in adult patients with frequent recurrence of this arrhythmia. This was a randomized, double-blind, 43-patient crossover study. Digoxin increased the mean time between symptomatic recurrent episodes by 54%, but had no effect on the frequency of fibrillatory episodes seen during continuous electrocardiographic monitoring.
BACKGROUND: Macrophage-derived matrix metalloproteinase 12 (MMP12) can cause destruction of lung tissue structure and plays a significant role in the development and progression of chronic obstructive pulmonary disease (COPD). MTOR is a serine/threonine kinase that plays a crucial role in cell growth and metabolism. The activity of MTOR in the lung tissues of COPD patients also shows significant changes. However, it is unclear whether MTOR can regulate the development and progression of COPD by controlling MMP12. This study primarily investigates whether MTOR in macrophages can affect the expression of MMP12 and participate in the progression of COPD.
METHODS: We tested the changes in MTOR activity in macrophages exposed to cigarette smoke (CS) both in vivo and in vitro. Additionally, we observed the effect of MTOR on the expression of MMP12 in macrophages and on lung tissue inflammation and structural damage in mice, both in vivo and in vitro, using MTOR inhibitors or gene knockout mice. Finally, we combined inhibitor treatment with gene knockout to demonstrate that MTOR primarily mediates the expression of MMP12 through the NF-κB signaling pathway.
RESULTS: Exposure to CS can enhance MTOR activity in mouse alveolar macrophages. Inhibiting the activity of MTOR or suppressing its expression leads to increased expression of MMP12. Myeloid-specific knockout of MTOR expression can promote the occurrence of CS-induced pulmonary inflammation and emphysema in mice. Inhibiting the activity of NF-κB can eliminate the effect of MTOR on MMP12.
CONCLUSION: Macrophage MTOR can reduce the expression of MMP12 by inhibiting NF-κB, thereby inhibiting the occurrence of COPD inflammation and destruction of lung tissue structure. Activating the activity of macrophage MTOR may be beneficial for the treatment of COPD.
Cutaneous burn trauma, compromise of dermal layers and immune defense system is a physical and fiscal burden on healthcare systems. Burn-wound infections are a serious complication of thermal injury and contribute significantly to care burden. After burn-induced trauma, sepsis by Pseudomonas aeruginosa impairs patient recovery and contributes to mortality and morbidity. Past studies show positive correlation between detection of Pseudomonas species and healing-impaired traumatic wounds. Pseudomonas aeruginosa is a resilient opportunistic human pathogen and a nosocomial agent involved in pathology of healing-impaired wounds, especially in burn patients. Expansive array of virulence determinants has resulted in gentamicin- and silver-resistant P. aeruginosa outbreaks. Knowledge of molecular dynamics and phylogeny of P. aeruginosa associated with burn wounds is limited. Therefore, we conducted whole-genome sequencing for genotyping and phylogenetic analysis of P. aeruginosa burn-associated strains (n = 19) isolated from 7 burn cases during hospitalization. Comparison of genetic features in P. aeruginosa strains in the core genome and mobilome detected genetic variations within some clonal infections over time. Genetic variations were observed among different burn cases, with some features identified in severe lung infections. Polyclonal infections were also observed, with differing genotypes and virulence potentials, highlighting the importance of reasoned sampling of isolates for clinical testing.
The present disclosure provides the first asymmetric total synthesis and target identification of the curcusone natural products. The novel convergent synthesis is built upon a cheap and abundant chiral pool molecule (8) and features a thermal [3,3]-sigmatropic rearrangement and an FeCl3-promoted global hydrolysis/adol condensation cascade to rapidly construct the critical cycloheptadienone core. By performing chemoproteomics with the alkyne probe 37, we identified the previously "undruggable" oncogenic protein BRAT1 as a key cellular target of 1d. Furthermore, 1d inhibits BRAT1 in cancer cells, thereby reducing cancer cell migration, increasing susceptibility to DNA damage, and inducing chemosensitization to the approved drug etoposide. Compound 1d is the first known small-molecule inhibitor for BRAT1, a master regulator of the DDR and DNA repair. Composition matters and methods of uses are within the scope of this disclosure.
The invention relates to a dried alum leukorrhea-clearing pill which is prepared from 100 g of dried alum, 12 g of schizandra sinensis, 5 g of peach kernel, 10 g of verdigris, 10 g of indigo and a little of realgar. 120 g of honey is added to the fine powder of the medicines to obtain a mixture, and the mixture is processed into pills each of which is 1.5-2g. The pill is used by taking one pill, wrapping with flimsy cloth, binding with cotton thread, and then placing in vagina while leaving the cotton thread tip at the external port of the vagina. After a course of treatment, namely 2-3 days, the pill is drawn out and another pill is placed, and disease is cured after 3-4 courses of treatment. In the prescription, dried alum is prepared by calcining alum to be bitter and dried, and has the effects of eliminating dampness, converging and relieving itching, eliminating inflammation and sterilizing, astringing to arrest bleeding, resolving phlegm, detoxifying as well as beautifying and resisting aging; schizandra sinensis has the effects of relieving cough and converging as well as moistening kidneys and promoting production of body fluid; the peach kernel is mainly used for treating blood stasis as well as hot and dry itching of skin; the verdigris is used for disinfecting, eliminating slough and nourishing qi and blood of women; the indigo is mainly used for dissipating phlegm fire of five internal organs, eliminating disease heat and treating postpartum bruise of women; and realgar is mainly used for detoxifying, eliminating inflammation, eliminating dampness and sterilizing. The prescription combination has the characteristics of detoxifying, eliminating inflammation, eliminating dampness, relieving itching, eliminating slough, converging, treating colored vaginal discharge, clearing away heat and toxic materials, sterilizing, controlling leukorrhea, contracting vagina, beautifying and maintaining health.
For advanced proximal gastric cancer, total gastrectomy with D2 lymphadenectomy is the standard surgical therapy. Apparently, lymph nodes (LNs) dissection along the splenic artery (No.11) and the splenic hilum (No.10) is recommended by the Japanese Gastric Cancer Treatment Guidelines. Nevertheless, complete removal of the No. 10 and No. 11d LNs is technically challenging due to the tortuous splenic vessels and the high possibility of injury to the parenchyma of the spleen and pancreas. Recently, the application of minimally invasive surgery for advanced gastric cancer is gaining popularity. However, laparoscopic-assisted total gastrectomy (LATG) with standard D2 lymphadenectomy was still not widely performed, because pancreas- and spleen-preserving splenic hilum lymph node dissection were mainly challenging manipulations for laparoscopic surgeons. Herein, we aim to investigate the safety and feasibility of LATG with spleen-preserving splenic hilum lymph node dissection for proximal advanced gastric cancer and compares the early results of this procedure with open total gastrectomy (OTG).
PURPOSE:To obtain a protein in high homogeneity and yield by using a transformant transformed with a specific vector and culturing the transformant in a medium. CONSTITUTION:A protein BBRP42 (a) is produced by culturing Bacillus brevis 47 strain and separating a supernatant at the initial stage of cultivation. A gene coding the component (a) is analyzed to obtain a DNA (b) composed of a base sequence of formula II (J is A or C; R is A or G) coding a signal peptide of formula I. A vector (e) such as pEGF-2 is produced by integrating the component (b), a DNA (c) coding a desired foreign protein (e.g. human epidermal growth factor) linked to the downstream terminal of the component (b), a promoter (d) having >=30 base pairs of the base sequence of formula III, etc. The component (e) is introduced into a Bacillus brevis, the obtained transformant (f) is cultured at about 37 deg.C and the obtained supernatant of the culture product is extracted and purified to obtain the objective protein such as human epidermal growth factor.
PCT No. PCT/EP97/03709 Sec. 371 Date Jun. 23, 1999 Sec. 102(e) Date Jun. 23, 1999 PCT Filed Jul. 7, 1997 PCT Pub. No. WO98/01436 PCT Pub. Date Jan. 15, 1998A compound of formula (I) or a salt thereof, or a solvate thereof, wherein: R1 represents an alkyl group or a substituted or unsubstituted aryl group; R2, R3 and R4 each independently represent hydrogen, alkyl, aryl or substituted aryl; R5 and R6 each independently represent hydrogen, hydroxy, amino, alkoxy, optionally substituted aryloxy, optionally substituted benzyloxy, alkylamino, dialkylamino, halo, trifluoromethyl, trifluoromethoxy, nitro, alkyl, carboxy, carbalkoxy, carbamoyl, alkylcarbamoyl, or R5 and R6 together represent methylenedioxy, carbonyldioxy or carbonyldiamino; X represents a hydroxy or an alkoxy group wherein the alkyl group may be substituted or unsubstituted or X represents a group NRSRt wherein RS and Rt each independently represent hydrogen, alkyl, substituted alkyl, optionally substituted alkenyl, optionally substituted aryl, optionally substituted arylalkyl, an optionally substituted heterocyclic group or an optionally substituted heterocyclylalkyl group, or RS and Rt together with the nitrogen to which they are attached form a heterocyclic group; and Y represents O or S and Z represents CH, CH=CH or N; or Y represents NR7 wherein R7 represents hydrogen, hydroxy, alkanoyl, alkyl, aminoalkyl, hydroxyalkyl, carboxyalkyl, carbalkoxyalkyl, carbamoyl or aminosulphonyl and Z represents CH=CH or N; a pharmaceutical composition containing such a compound, a process for preparing such a compound and the use of such a compound in medicine.