anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Described is an RNA molecule comprising (a) a region coding for a regulator of energy homeostasis like GLP-1 and/or GDF-15; and (b) upstream of said coding region one (or more) UTR(s) comprising (A) the sequence as shown in SEQ ID NO:1 or SEQ ID NO:40 or a functional derivative thereof; or (B) the 5'-UTR of alpha globin (Ag) or a functional derivative thereof; and/or (c) downstream of said coding region one or more UTR(s) comprising the sequence as shown in SEQ ID NO:2 or a functional derivative thereof. Further described is a set of 2 or more RNA molecules, wherein the coding region of one RNA molecule codes for one regulator of energy homeostasis (like GLP-1) and wherein the coding region of another RNA molecule codes for another such regulator (like GDF-15). Moreover, described is a nucleic acid molecule encoding the RNA molecule or the set of RNA molecules and a set of 2 or more nucleic acid molecules encoding the 2 or more RNA molecules, respectively, of the set of the 2 or more RNA molecules. Further described are respective vectors and host cells and respective sets of vectors and host cells. Further described is a pharmaceutical composition comprising the RNA molecule, nucleic acid molecule, vector or host cell according to the present invention, or the respective set. Also described is a kit comprising the RNA molecule, nucleic acid molecule, vector or host cell according to the present invention, or the respective set. Further described is the pharmaceutical composition of the invention for use in an RNA-based therapy and/or as an anorectic; in body weight control, in particular in decreasing (aberrant) body weight; and/or in the treatment or prevention of a metabolic disorder/metabolic syndrome. Also described are respective methods for (medical) intervention. Finally, described is the use of one or more UTR(s) as defined in (b) and/or one or more UTR(s) as defined in (c) in increasing the efficiency of translating a coding region of an RNA molecule into a regulator of energy homeostasis like GLP-1 and/or GDF-15 (MIC-1) encoded by said coding region.
Participants will receive the Nanodropper with instructions and attend clinic visits at baseline, 1, and 3 months. Participants will administer their eye drops using the Nanodropper.
The study will be conducted in 2 parts: Part 1 - Dose Escalation and Part 2 - Dose Expansion. Part 1 is aimed at evaluating the safety, tolerability, PK and pharmacodynamics of SY-5933 and determining the recommended phase II dose (RP2D) of repeat daily (QD) dosing schedule in subjects with advanced KRAS p.G12C mutant solid tumors using accelerated titration and 3+3 design. The dose escalation part of the study will consist of 7-13 subjects and the dose expansion part will consist of 30-60 additional subjects, comprising 2 cohorts. Cohort A includes patients with non-small cell lung cancer (NSCLC) harboring KRAS p.G12C mutations and Cohort B includes patients with other advanced solid tumors (colorectal, pancreatic cancers, etc.). Patients in dose expansion study will receive SY-5933 tablets QD, oral administration, 28 days as a dosing cycle, to further evaluate the safety, PK profile, and efficacy of SY-5933, and to further define RP2D. Administration of SY-5933 may continue until evidence of disease progression, intolerance to SY-5933, or withdrawal of consent.
<P>PROBLEM TO BE SOLVED: To provide an antibody against human parathyroid hormone-related peptides.  <P>SOLUTION: An antibody against the human parathyroid hormone-related peptides. A DNA encoding the antibody. A recombinant vector containing the DNA. A transformant transformed with the recombinant vector. A method for producing the antibody. And the use of the antibody. The antibody is useful as a medicine for improving the clinical various syndromes of hypercalcemia accompanied by malignant tumor.  <P>COPYRIGHT: (C)2003,JPO
This prospective cohort study will evaluate rates of virologically confirmed influenza in children attending schools with and without school-based vaccination programs. Eight schools (4455 students) in two school districts matched for size, race/ethnicity, socioeconomic status, and location will serve as intervention and control schools. During influenza season defined by local surveillance data, nasal/throat swabs will be obtained for rapid influenza detection assays from all children with fever and respiratory symptoms identified by teachers for evaluation in the school nurse's office. Absent children will be offered testing at a central location within the schools' communities.Rates of confirmed influenza illness in vaccinated and non-vaccinated children will be compared between schools with and without vaccination programs. Rates of absenteeism also will be evaluated. The investigators hypothesize that in addition to lowering rates of influenza in vaccinated children, raising vaccination rates by 30-40% through school-based vaccination programs will decrease incidence of influenza in non-vaccinated children attending those schools compared to non-vaccinated children in schools with low vaccination rates.
Glass Box Machine Learning is, in this study, a type of partially supervised data mining and prediction technique, like a neural network in which each weight or pattern of mutually relevant weights is now replaced by a meaningful "probabilistic knowledge element." We apply it to retrospective cohort studies using large numbers of structured medical records to help select candidate patients for future cohort studies and similar clinical trials. Here it is applied to aid analysis of approaches to aid Deep Learning, but the method lends itself well to direct computation of odds with "explainability" in study design that can complement "Black Box" Deep Learning. Cohort studies and clinical trials traditionally involved at least one 2 × 2 contingency table, but in the age of emerging personalized medicine and the use of machine learning to discover and incorporate further relevant factors, these tables can extend into many extra dimensions as a 2 × 2 x 2 × 2 x ….data structure by considering different conditional demographic and clinical factors of a patient or group, as well as variations in treatment. We consider this in terms of multiple 2 × 2 x 2 data substructures where each one is summarized by an appropriate measure of risk and success called DOR*. This is the diagnostic odds ratio DOR for a specified disease conditional on a favorable outcome divided by the corresponding DOR conditional on an unfavorable outcome. Bleeding peptic ulcer was chosen as a complex disease with many influencing factors, one that is still subject to controversy and that highlights the challenges of using Real World Data.
The proposed study will test the conceptual model positing that acute alcohol alters the relative bias in computational mechanisms for threat vs reward, thereby decreasing avoidance to threat and increasing approach to reward in adults with PTSD, and through this mechanism increases risk for heavier alcohol use over time. Research aims are to identify alcohol-induced changes in approach-avoidance decision-making and mediating neural networks that predict alcohol use and symptoms of AUDs over a one-year follow-up period in adults with PTSD, compared to adults with interpersonal violence exposure but no PTSD and healthy comparison adults. Essential to successfully improving clinical prognosis in PTSD are research results that enable better prediction, diagnosis, and treatment based on the individual. There is a paucity of human clinical research investigating interactions between acute alcohol exposure and PTSD that may drive risk for development of AUDs following trauma. Data could identify brain and behavioral mechanisms explaining how alcohol alters an important domain of PTSD contributing to risk for alcohol misuse and development of alcohol problems. Results could pave way for development of novel behavioral and pharmacological methods to treat PTSD and decrease risk for developing comorbid AUDs.
BACKGROUND: 5-Fluorouracil (5-FU) is used as an antineoplastic agent in distinct cancer types. Increasing evidence suggests that the gut microbiota might modulate 5-FU efficacy and toxicity, potentially affecting the patient's prognosis. The current experimental study investigated 5-FU-induced microbiota alterations, as well as the potential of prebiotic fibre mixtures (M1-M4) to counteract these shifts.
METHODS: A pooled microbial consortium was derived from ten healthy donors, inoculated in an in vitro model of the colon, and treated with 5-FU, with or without prebiotic fibre mixtures for 72 h. Four different prebiotic fibre mixtures were tested: M1 containing short-chain galacto-oligosaccharides (sc GOS), long-chain fructo-oligosaccharides (lcFOS), and low viscosity pectin (lvPect), M2 consisting of arabinoxylan, beta-glucan, pectin, and resistant starch, M3 which was a mixture of scGOS and lcFOS, and M4 containing arabinoxylan, beta-glucan, pectin, resistant starch, and inulin.
RESULTS: We identified 5-FU-induced changes in gut microbiota composition, but not in microbial diversity. Administration of prebiotic fibre mixtures during 5-FU influenced gut microbiota composition and taxa abundance. Amongst others, prebiotic fibre mixtures successfully stimulated potentially beneficial bacteria (Bifidobacterium, Lactobacillus, Anaerostipes, Weissella, Olsenella, Senegalimassilia) and suppressed the growth of potentially pathogenic bacteria (Klebsiella, Enterobacter) in the presence of 5-FU. The short-chain fatty acid (SCFA) acetate increased slightly during 5-FU, but even more during 5-FU with prebiotic fibre mixtures, while propionate was lower due to 5-FU with or without prebiotic fibre mixtures, compared to control. The SCFA butyrate and valerate did not show differences among all conditions. The branched-chain fatty acids (BCFA) iso-butyrate and iso-valerate were higher in 5-FU, but lower in 5-FU + prebiotics, compared to control.
CONCLUSIONS: These data suggest that prebiotic fibre mixtures represent a promising strategy to modulate 5-FU-induced microbial dysbiosis towards a more favourable microbiota, thereby possibly improving 5-FU efficacy and reducing toxicity, which should be evaluated further in clinical studies.
CONTEXT: Cardiovascular disease (CVD) is the leading cause of death in the United States. As such, an unmet need exists in the primary and secondary prevention of adverse cardiovascular events (CVEs). Specifically, identifying drugs that can reduce the progression of CVD and serious adverse events is much needed. Drugs that work by reducing platelet aggregation, blocking cholesterol formation (3-hydroxy-3-methyl-glutaryl-coenzyme A [HMG-CoA] reductase inhibitors), and/or blocking inflammation pathways (mainly interleukin-1b [IL-1b]) have been linked to preventing adverse CVEs, including acetylsalicylic acid (ASA, aspirin), statins, colchicine, and IL-1 inhibitors (interleukin-1 receptor antagonists). This systematic review aims to provide insight into utilizing these four agents for the primary and/or secondary prevention of CVD.
OBJECTIVES: In this systematic review, we opted to review the efficacy of aspirin, statins, colchicine, and IL-1 inhibitors in the primary and secondary prevention of CVE to provide clinical practitioners with evidence-based practice approaches and determine any unmet needs in their utilization.
METHODS: Between October 1 and 12, 2021, a search was conducted and completed on five databases: PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, and Biomedical Reference Collection: Comprehensive. A total of 13 researchers (V.A., A.H., S.B., V.G., D.C., C.C., C.B., C.A., S.K., J.H., A.K., S.F., and S.E.) were involved in the search and screening of the articles. Search terms included "aspirin, statins, colchicine, IL-1 inhibitors, and primary, secondary, myocardial infarction (MI)." Inclusion criteria included clinical study design, English language articles, all genders older than 50 years old, and established patient history of CVD, including MI. In addition, articles were excluded if they were animal models, in vitro studies, pharmacokinetic studies, systematic reviews, literature reviews, and studies exploring therapies other than those listed in the inclusion criteria. First, five individuals independently sorted through abstracts or articles based on the inclusion and exclusion criteria. Then, a team of 13 individuals sorted through full-text articles of selected abstracts based on the same criteria. A separate researcher resolved conflicts between the team.
RESULTS: A total of 725 articles were identified from all databases, from which 256 duplicated articles were removed. Thus, a total of 469 articles abstracts were screened, of which 425 articles either did not meet the inclusion criteria or met the exclusion criteria. A total of 42 articles were retrieved and assessed for full-text review, from which 15 articles were retrieved for analysis.
CONCLUSIONS: Statins may prevent primary CVEs based on their role in preventing cholesterol formation. Aspirin, canakinumab, and colchicine may be helpful in the secondary prevention of CVEs due to their blocking of various steps in the inflammation pathway leading to CVD. Future research should primarily focus on the use of canakinumab and colchicine in preventing CVD due to the limited number of studies on these drugs.
The present invention relates to anthracycline derivatives that are based on an Aloe-emodin (AE) backbone attached to a glycoside (an amino sugar or amino carba-sugar). These derivatives are useful as chemotherapeutic agents. Advantageously, these derivatives are potent cytotoxic agents against a variety of anthracycline-resistant tumors. In addition, they may have reduced cardiotoxicity. As such, the novel compounds of the invention offer an advantage over currently available drugs. The present invention further relates to methods for preparing the novel Aloe-Emodin Glycoside (AEG) based derivatives, pharmaceutical compositions including such compounds, and methods of using these compounds and compositions, especially as chemotherapeutic agents for prevention and treatment of cancers.
BACKGROUND: There is a paradigm shift in the management of locally advanced rectal cancer (LARC) from conventional neoadjuvant treatment to total neoadjuvant therapy (TNT). Despite its growing acceptance, there are limited studies that have examined its effects on disease presentation. In addition, it is important to determine the factors that play a role in complete response (CR). Our previous data from 119 patients revealed that the CR rate was 37%, and low rectal tumors and the absence of extramural vascular invasion (EMVI) were predictors of CR. Unfortunately, there continues to be a lack of data, and reliable markers are still needed to consistently identify the best respondents. Therefore, this study aimed to determine the factors associated with CR. Moreover, this study hypothesized that both predictive factors and the CR ratio might evolve over time because of the growing patient population.
METHODS: This retrospective study included patients who completed TNT for LARC at our tertiary care center between 2015 and 2022. The primary outcome was to determine the predictors of CR. The secondary outcomes were the 2-year disease-free survival (DFS) rate and overall survival (OS) rate. CR consists of patients who sustained clinical CR (cCR) for at least 12 months under watch and wait or had pathologic CR (pCR) after surgery.
RESULTS: Of 339 patients with LARC, 208 (61.3%) successfully completed TNT. Among 208 patients, 57 (27.4%) achieved cCR, and 166 (80.0%) sustained cCR without tumor regrowth after 1 year. The remaining 151 patients (72.6%) underwent surgery, and 42 patients had pCR. The final CR rate was 42.3%. The median age of the patients was 56 years (IQR, 49-66). Moreover, 132 participants (63.5%) were male, whereas 76 participants (36.5%) were female. The median tumor size was 4.95 cm (IQR, 3.60-6.43), with most tumors in the low rectum (119 [57.2%]). Based on the MRI findings, the mesorectal facia (MRF) involvement rate was 25.0% (n = 52), and EMVI was observed in 43 patients (20.7%). Low rectal tumors, the absence of MRF involvement, and the absence of EMVI were predictors of CR. With a median follow-up of 24.7 months, 2-year DFS and OS were significantly higher among patients with CR than among patients with incomplete response (91.3% vs 71.0% [P < .01] and 98.8% vs 90.2% [P = .03], respectively).
CONCLUSION: An increasing CR rate was observed in our updated dataset compared with that in our previous study. In addition to previously identified predictors, low tumor location, and the absence of EMVI, the absence of MRF involvement was determined as a predictor of CR. Our findings offer valuable insights into clinical practice and help clinicians set clear expectations when counseling patients.
The experimental intervention is an integrative mindful compassion group therapy as manualized by Cheli, Cavalletti, Flett \& Hewitt (2020). The structure was outlined on the base of standard mindfulness-based interventions, comprising eight 2-hour online group sessions and one day of silence lasting 4 hours. The contents and the phases of the intervention were rooted in two different frameworks. On the one hand, the sequence of and the types of practices were defined in accordance with the mindful compassion protocol (Gilbert \& Choden, 2014). On the other hand, the shared conceptualization of perfectionism and its role in triggering, maintaining, and inducing relapses in personality disoders was proposed through the relational model by Hewitt and colleagues (2017). The hybrid format (online weekly sessions plus an in presence half-day of silence) has been developed in accordance with existing COViD-19 emergency and rules.
The RNA modification, 5-methylcytosine (m5C), has recently gained prominence as a pivotal post-transcriptional regulator of gene expression, intricately intertwined with various tumorigenic processes. However, the exact mechanisms governing m5C modifications during the onset and progression of colorectal cancer (CRC) remain unclear. Here, it is determined that the m5C methyltransferase NSUN2 exhibits significantly elevated expression and exerts an oncogenic function in CRC. Mechanistically, NSUN2 and YBX1 are identified as the "writer" and "reader" of ENO1, culminating in the reprogramming of the glucose metabolism and increased production of lactic acid in an m5C-dependent manner. The accumulation of lactic acid derived from CRC cells, in turn, activates the transcription of NSUN2 through histone H3K18 lactylation (H3K18la), and induces the lactylation of NSUN2 at the Lys356 residue (K356), which is crucial for capturing target RNAs. Together, these findings reveal an intriguing positive feedback loop involving the NSUN2/YBX1/m5C-ENO1 signaling axis, thereby bridging the connection between metabolic reprogramming and epigenetic remodeling, which may shed light on the therapeutic potential of combining an NSUN2 inhibitor with immunotherapy for CRC.
Patients will be treated with PCI-32765 capsules administered orally once daily at a dose of 420 mg for 28 day cycles. Weekly monitoring during the first month will occur followed by monthly evaluations for 2 additional months. Monitoring for patients at this point would be every 3 months with monthly CBC(complete blood count)and phone follow-up with a co-investigator on the study. A standard questionnaire will be used in this monthly phone assessment. Patients will continue to receive the study drug indefinitely as long as they are deriving clinical benefit (Complete Response or Partial Response or Stable Disease) and not experiencing any unacceptable toxicity. Subjects with disease progression will be removed from the study. Correlative laboratory samples, quality of life assessment, and immunologic data would be collected over time of therapy.
A magnetic material having a magnetic heating efficiency of at least 4.5 x 10-8 J.m/A.g in a cyclic magnetic field where the product of the amplitude and frequency of the applied field is less than or equal to 5 x 108 A/m.s, and the frequency of the applied field is at least 20kHz. The ideal magnetic material is characterised by a perfectly rectangular hysteresis loop, i.e. loop squareness of 1, with coercivity of 25kA/m or less and high saturation magnetisation. Preferably the magnetic material has a predominantly cubic magnetic crystalline anisotropy. Preferably the magnetic material is a substituted magnetite (Fe3O4) or .gamma.-ferric oxide (.gamma.-Fe2O3) crystalline lattice in which some of the iron atoms in that crystalline lattice have been substituted for one or more alternate metal atoms.  Desirably, the metal atom is a member of the group: cobalt, zinc, nickel, manganese, magnesium, copper, chromium, galliun, cadmium.
Compositions comprising polymers comprising one or more ketal, monothioketal, and/or thioketal bonds are provided, as well as related methods and kits. In some embodiments, a polymer may comprise one or more repeat units comprising one or more ketal, monothioketal, and/or thioketal bonds and a precursor of a pharmaceutically active agent. The precursor of the pharmaceutically active agent may be located in the backbone or may be a pendant group. The polymer may degrade in certain environments (e.g., aqueous environments, acidic environments, in vivo, etc.) to produce the pharmaceutically active agent and other biocompatible degradation f) products, such as certain ketones, alcohols, and/or thiols. Regardless of the location of the precursor of the pharmaceutically active agent in the repeat unit(s), the polymer may have a prolonged degradation time and/or release of the pharmaceutically active agent in certain environments. Various compositions, described herein, may be particularly well suited for applications requiring extended release of pharmaceutically active agents, such as the treatment of ophthalmic disorders.
A sexual hygienic composition comprises milk extract prepared from the milk of at least one equid animal, optionally combined with additive(s). ACTIVITY : Endocrine-Gen.; Antiinflammatory; Antibacterial; Contraceptive. 58 women participated in the study. All participants were older than 52 years and all had a feeling of vaginal dryness of varying intensity before the study started. An effervescent tablet (A) (2000) (prepared using the following ingredients sodium hydrogen carbonate, lactose, and powder mad of ass milk) and a comparative tablet (B) (similarly prepared as tablet A, except using ass milk powder) were applied for irrigation once a day with the Colpo-Cleaner irrigator. Women with odd birthdates used tablet (A) while women with even birthdates used tablets (B). After 5 weeks of 10 days 35 of the original participants returned for control consultation, out of which 18 had been applying tablet (A), and 17 tablet (B). Test evaluation was carried out by a third person, who established that randomized double-blind study showed detectable difference between the two groups. Of group using tablet (A) one person, while of participants of the group using tablet (B) four persons, said that the feeling of vaginal dryness had not become less intensive during the irrigation period. The initial irritation/itching caused by the irrigation liquid had not ceased in the case of three participants using tablet (A), while the others mentioned a slight remnant feeling irritation/itching only after having been asked targeted questions. Of the group using tablet (B) six women said that the feeling of irritation/itching had not ceased, while to targeted questions six other women responded that a dim feeling of irritation/itching remained. The study showed that the application of tablet (A), containing a very small amount of ass milk preparation, lead to better results. MECHANISM OF ACTION : Bacterial growth inhibitor.