anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Matrix metalloproteinase 9 (MMP-9) is a member of the MMP family and has been recently identified as a nuclear protease capable of clipping histone H3 N-terminal tails (H3NT). This MMP-9-dependent H3NT proteolysis is critical for establishing an active state of gene transcription during osteoclast differentiation and melanoma development. However, whether H3NT cleavage by MMP-9 plays a similar role in other cellular events has not been explored. Here, we dissect the functional contribution of MMP-9-dependent H3NT clipping to colonic tumorigenesis by using a combination of genome-wide transcriptome data, ChIP/ChIPac-qPCR, CRISPR/dCas9 gene-targeting system, and in vivo xenograft models. We show that MMP-9 is overexpressed in colon cancer cells and catalyzes H3NT proteolysis to drive transcriptional activation of growth stimulatory genes. Our studies using knockdown and inhibition approaches clearly indicate that MMP-9 mediates transcriptional activation and promotes colonic tumorigenesis in a manner dependent on its protease activity toward H3NT. Remarkably, artificial H3NT proteolysis at target gene promoters with dCAS9-MMP-9 is sufficient for establishing their transcriptional competence in colon cancer cells, underscoring the importance of MMP-9-dependent H3NT proteolysis per se in the transactivation process. Our data establish new functions and mechanisms for MMP-9 in driving the oncogenic transcription program in colon cancer through H3NT proteolysis, and demonstrate how this epigenetic pathway can be exploited as a potential therapeutic target for cancer treatment.
GMT modules were adapted for French-speaking patients with PD-MCI. Each session was reduced from nine 90-120-minute sessions (original GMT) to five 60-90-minute sessions, one session per week, in order to avoid fatigue. As for original GMT, participants were given exercises between sessions (mindfulness exercises and metacognitive reflections). In original-GMT, some information is repeated several times, but not in Adapted-GMT. Exercises demanding motor dexterity, such as card distribution, were removed. Adapted-GMT included information on PD-MCI and executive dysfunction (some psychoeducation). In addition, Adapted-GMT modules were administered individually with an iPad, as opposed to a power-point group presentation in original-GMT. A workbook was handed to participants, as in previous studies.
Fatigue is a frequent symptom of cancer and the most common adverse event of treatment with tyrosine kinase inhibitors. For example, in phase 2 randomized study 59% of patients with metastatic renal cell carcinoma experienced any grade fatigue during treatment with the combination of lenvatinib and everolimus. Fourteen percent of patients had grade 3 fatigue or asthenia. Fatigue was also most frequently reported treatment-related adverse event in patients with unresectable hepatocellular carcinoma (30%), and advanced thyroid cancer (60%) treated with lenvatinib. Additionally, fatigue is one of the most common adverse events associated with the administration of checkpoint inhibitors. Frequency of fatigue was 55% in patients with endometrial cancer treated with combination of pembrolizumab and lenvatinib.

Meldonium is a fatty acid oxidation inhibitor, and it is now principally used for heart conditions, such as angina, heart attack, heart failure, and others. The compound works by altering pathways for carnitine, a nutrient involved in fat metabolism. Meldonium received the greatest fame in sport. The World Anti-Doping Agency (WADA) added meldonium to their list of banned substances in 2016 because of evidence of its use by athletes with the intention of enhancing performance. Center for Preventive Doping Research and European Monitoring Center for Emerging Doping Agents showed that mildronate demonstrates an increase in endurance performance of athletes, improved rehabilitation after exercise, protection against stress, and enhanced activations of the central nervous system functions. Based on these data, meldonium can be a possible option in cancer patients with fatigue treated with targeted or imminotargeted therapy. Moreover, the compound could decrease the number of vascular adverse events of TKIs.
1. All patients receiving intravenous oxytocin must be under continuous observation by trained personnel who have a thorough knowledge of the drug and are qualified to identify complications. A physician qualified to manage any complications should be immediately available. Electronic fetal monitoring provides the best means for early detection of overdosage (see OVERDOSAGE section). However, it must be borne in mind that only intrauterine pressure recording can accurately measure the intrauterine pressure during contractions. A fetal scalp electrode provides a more dependable recording of the fetal heart rate than any external monitoring system.
  2. When properly administered, oxytocin should stimulate uterine contractions comparable to those seen in normal labor. Overstimulation of the uterus by improper administration can be hazardous to both mother and fetus. Even with proper administration and adequate supervision, hypertonic contractions can occur in patients whose uteri are hypersensitive to oxytocin. This fact must be considered by the physician in exercising his judgment regarding patient selection.
  3. Except in unusual circumstances, oxytocin should not be administered in the following conditions: fetal distress, hydramnios, partial placenta previa, prematurity, borderline cephalopelvic disproportion, and any condition in which there is a predisposition for uterine rupture, such as previous major surgery on the cervix or uterus including cesarean section, overdistention of the uterus, grand multiparity, or past history of uterine sepsis or of traumatic delivery. Because of the variability of the combinations of factors which may be present in the conditions listed above, the definition of "unusual circumstances" must be left to the judgment of the physician. The decision can be made only by carefully weighing the potential benefits which oxytocin can provide in a given case against rare but definite potential for the drug to produce hypertonicity or tetanic spasm.
  4. Maternal deaths due to hypertensive episodes, subarachnoid hemorrhage, rupture of the uterus, and fetal deaths due to various causes have been reported associated with the use of parenteral oxytocic drugs for induction of labor or for augmentation in the first and second stages of labor.
  5. Oxytocin has been shown to have an intrinsic antidiuretic effect, acting to increase water reabsorption from the glomerular filtrate. Consideration should, therefore, be given to the possibility of water intoxication, particularly when oxytocin is administered continuously by infusion and the patient is receiving fluids by mouth.
  6. When oxytocin is used for induction or reinforcement of already existent labor, patients should be carefully selected. Pelvic adequacy must be considered and maternal and fetal conditions evaluated before use of the drug.
NEW MATERIAL:The compound of formula I (only one of the dotted lines is C-C double bond; R is 1-5C alkyl). EXAMPLE:Ethyl alpha-monocyclofarnesylacetate. USE:Useful as an agent for imparting or modifying fragrance, a synthetic raw material of other perfume, pharmaceuticals, etc., or their intermediate. It has fragrance of floral note and having excellent durability. Excellent effect can be obtained by adding to foods, drinks, soap, detergent, cosmetics, sanitary goods, pharmaceuticals, and various other materials. PROCESS:The monocyclofarnesyl of formula 1 can be prepared by reacting the compound of formula 5 with MgX of formula 4 in the absence or presence of e.g. an organic solvent, reacting the reaction product with a compound including the novel compound of formula 3, and reacting the product with the orthoacetic acid ester of formula 2 in the presence of an acid (e.g. acetic acid, propionic acid, etc.).
Recent advances in genomics and proteomics have helped in understanding the molecular mechanisms and pathways of comorbidities and heart failure. In this narrative review, we reviewed molecular alterations in common comorbidities associated with heart failure such as obesity, diabetes mellitus, systemic hypertension, pulmonary hypertension, coronary artery disease, hypercholesteremia and lipoprotein abnormalities, chronic kidney disease, and atrial fibrillation. We searched the electronic databases, PubMed, Ovid, EMBASE, Google Scholar, CINAHL, and PhysioNet for articles without time restriction. Although the association between comorbidities and heart failure is already well established, recent studies have explored the molecular pathways in much detail. These molecular pathways demonstrate how novels drugs for heart failure works with respect to the pathways associated with comorbidities. Understanding the altered molecular milieu in heart failure and associated comorbidities could help to develop newer medications and targeted therapies that incorporate these molecular alterations as well as key molecular variations across individuals to improve therapeutic outcomes. The molecular alterations described in this study could be targeted for novel and personalized therapeutic approaches in the future. This knowledge is also critical for developing precision medicine strategies to improve the outcomes for patients living with these conditions.
Controlled Substance Class

Celexa (citalopram HBr) is not a controlled substance.

Physical and Psychological Dependence

Animal studies suggest that the abuse liability of Celexa is low. Celexa has not been systematically studied in humans for its potential for abuse, tolerance, or physical dependence. The premarketing clinical experience with Celexa did not reveal any drug-seeking behavior. However, these observations were not systematic and it is not possible to predict, on the basis of this limited experience, the extent to which a CNS-active drug will be misused, diverted, and/or abused once marketed. Consequently, physicians should carefully evaluate Celexa patients for history of drug abuse and
APRISO is an aminosalicylate, and symptoms of salicylate toxicity include hematemesis, tachypnea, hyperpnea, tinnitus, deafness, lethargy, seizures, confusion, or dyspnea. Severe intoxication may lead to electrolyte and blood pH imbalance and potentially to other organ (e.g., renal and liver) involvement. There is no specific antidote for mesalamine overdose; however, conventional therapy for salicylate toxicity may be beneficial in the event of acute overdosage. This includes prevention of further gastrointestinal tract absorption by emesis and, if necessary, by gastric lavage. Fluid and electrolyte imbalance should be corrected by the administration of appropriate intravenous therapy. Adequate renal function should be maintained. APRISO is a pH-dependent delayed-release product and this factor should be considered when treating a suspected overdose.
Intensive Care Unit Sedation   
A total of 729 patients in the clinical studies were 65 years of age and over. A total of 200 patients were 75 years of age and over. In patients greater than 65 years of age, a higher incidence of bradycardia and hypotension was observed following administration of dexmedetomidine hydrochloride in 0.9% sodium chloride injection [see Warnings and Precautions (5.2)]. Therefore, a dose reduction may be considered in patients over 65 years of age [see Dosage and Administration (2.2, 2.3), Clinical Pharmacology (12.3)].   
  
Procedural Sedation   
A total of 131 patients in the clinical studies were 65 years of age and over. A total of 47 patients were 75 years of age and over. Hypotension occurred in a higher incidence in dexmedetomidine-treated patients 65 years or older (72%) and 75 years or older (74%) as compared to patients <65 years (47%). A reduced loading dose of 0.5 mcg/kg given over 10 minutes is recommended and a reduction in the maintenance infusion should be considered for patients greater than 65 years of age.
BACKGROUND: Lynch syndrome is a hereditary cancer predisposition syndrome caused by germline mutations in DNA mismatch repair genes, which lead to high microsatellite instability and frameshift mutations at coding mononucleotide repeats in the genome. Recurrent frameshift mutations in these regions are thought to play a central role in the increased risk of various cancers, but no biomarkers are currently available for the surveillance of high microsatellite instability-associated cancers.
METHODS: A frameshift mutation-based biomarker panel was developed and validated by targeted next-generation sequencing of supernatant DNA from cultured high microsatellite instability colorectal cancer cells. This panel supported selection of 122 frameshift mutation targets as potential biomarkers. This biomarker panel was then tested using matched tumor, adjacent normal tissue, and buffy coat samples (53 samples) and blood-derived cell-free DNA (cfDNA) (38 samples) obtained from 45 high microsatellite instability and mismatch repair-deficient patients. We also sequenced cfDNA from 84 healthy participants to assess background noise.
RESULTS: Recurrent frameshift mutations at coding mononucleotide repeats were detectable not only in tumors but also in cfDNA from high microsatellite instability and mismatch repair-deficient patients, including a Lynch syndrome carrier, with a varying range of target detection (up to 85.2%), whereas they were virtually undetectable in healthy participants. Receiver operating characteristic curve analysis showed high sensitivity and specificity (area under the curve = 0.94) of the investigated panel.
CONCLUSIONS: We demonstrated that frameshift mutations can be detected in cfDNA from high microsatellite instability and mismatch repair-deficient patients and asymptomatic carriers. The 122-target frameshift mutation panel described here has promise as a tool for improved surveillance of high microsatellite instability and mismatch repair-deficient patients, with the potential to reduce the frequency of invasive screening methods for this high-cancer-risk cohort.
OBJECTIVE: The pain-reducing effects of the exercise were exerted through different mechanisms. Knowing more clear mechanisms helps to find more approach that is therapeutic. The objective of the present study is the evaluation of cerebrospinal fluid (CSF) glutamate level alteration in neuropathic pain rats and whether physical activity could modulate it.
METHODS: In the present study 104 male Wistar rats weighing 180-220 g were randomly divided into 4 groups (Sham, Sham + Exe, Neuropathy, and Neuropathy + Exe) which in turn each group subdivided into 4 groups according to time points for behavioral testing and CSF sampling (Baseline, 2 weeks, 3 weeks, and 4 weeks). To induction of neuropathy (by chronic constriction injury,), after anesthetizing with a mixture of ketamine (80 mg/kg) and xylazine (10 mg/kg), the animal's right sciatic nerve was exposed and was ligated using four movable catgut chromic suture 4/0. The exercise protocol included 25 min of daily swimming, 5 days a week for 4 weeks. Thermal hyperalgesia and mechanical tactile threshold were detected using the plantar test and Von Frey filaments, respectively. CSF glutamate level was determined using high-performance liquid chromatography.
RESULTS: Findings indicated that mechanical and thermal thresholds significantly (p < 0.01, p < 0.05 respectively) decreased in the neuropathy group against that in sham groups. On the other hand, exercise significantly increased mechanical tactile threshold (p < 0.0012) and thermal threshold (p < 0.05) compared to the neuropathy group. Moreover, CSF glutamate level prominently (p < 0.01) was increased in the neuropathy group compared to the sham group, and swimming exercise significantly (p < 0.001) reduced it.
IN CONCLUSION: The present findings provide new evidence showing that medium-intensity swimming exercise attenuates pain-like behaviors in neuropathic pain animals, which is possibly due to decreasing CSF glutamate level and its neurotransmission.
A computer-generated randomization plan was used for assignment of subjects to one of six treatment sequences (4 subjects per sequence): oxymorphone/propoxyphene/placebo, oxymorphone/placebo/propoxyphene, placebo/oxymorphone/propoxyphene, placebo/propoxyphene/oxymorphone, propoxyphene/oxymorphone/placebo, or propoxyphene/placebo/oxymorphone. One dose of blinded study drug (opana, propoxypehen, or placebo) was given at study days 1, 5, and 9. The primary endpoint was time to first symptoms of moderate intensity (NRS ≥ 4/10) during treadmill ambulation. Ambulation assessment was performed during the screening visit. Ambulation assessment was also performed 90 minutes after administration of study drug on days 1, 5 and 9, to evaluate pain intensity associated with walking as well as distance covered by the patients. Quantitative assessment of ambulation was conducted on a treadmill at 0° ramp incline at 1.2 miles per hour (mph). Measurement of self-reported symptom severity using the NRS at baseline, and every 30 seconds for a maximum of 15 minutes was recorded. The following information was also recorded: time to first symptoms, total ambulation time. The examination was stopped after 15 minutes or at the onset of severe symptoms. Severe symptoms were defined as the level of discomfort that would make patients stop walking in usual life situations. No one was encouraged or prompted to continue walking beyond this point. Patients were instructed to walk with an upright posture. They were not permitted to lean forward or hold onto the handrails during the examination. Secondary outcome measures included area under the curve of present pain intensity with ambulation at each specified time point, final pain intensity with walking, walking tolerance, time to return to baseline pain level after ambulation, as well as the results of a series of pain related questionnaires including: Visual Analog Scale (VAS), Patient Global Assessment (PGA), NRS, Roland Morris Disability Questionnaire (RMDQ), modified Brief Pain Inventory short form (mBPI-sf), Oswestry Disability Index (ODI), and Swiss Spinal Stenosis (SSS).
Participants received ruxolitinib twice a day for 5 weeks. Participants were required to remain on ART regimen (not provided by the study) for the duration of the study.
Segmental forward maxillary distraction osteogenesis(DO)was performed. Distractor connecting buccal molar segments to the anterior maxilla was kept for 7 days. Then distraction was performed till overcorrection and consolidated for 3-months. Periodontal clinical parameters were recorded at baseline, 3 and 6-months postoperatively. Gingival crevicular fluid was collected . Soft tissue healing was evaluated clinically and histologically after distraction.
PURPOSE: Error related to incorrect use of rating scales is problematic in the assessment and treatment of dysarthria. The main purpose of this project was to determine scale fit for cardinal speech features of hypokinetic dysarthria. A secondary aim was to determine rater reliability for the two different scales explored.
METHOD: Forty-three speakers with Parkinson's disease (PD) and 25 neurologically healthy control talkers were recorded reading sentences from the Speech Intelligibility Test. Twenty-two healthy female listeners used both an equal appearing interval (EAI) scale and a direct magnitude estimation (DME) scale to rate five perceptual speech features (i.e., overall speech severity, articulatory imprecision, reduced loudness, short rushes of speech, and monotony) from these recordings. Regression analyses were used to determine the linearity of the relationship between the means of the EAI and DME ratings. Inter- and intrarater reliability was calculated using intraclass correlation coefficients and Spearman's correlation coefficients, respectively, for both EAI and DME ratings.
RESULTS: There was a linear relationship between EAI and DME means for monotony, indicating it is a metathetic dimension. Curvilinear relationships were observed between the EAI and DME means for the other four features, indicating prothetic dimensions. Intra- and interrater reliability values were similar for EAI and DME ratings.
DISCUSSION: Overall, results of this work suggest that DME is the best fit for scaling several hypokinetic dysarthria features, and not the conventionally used EAI scale. Prothetic dimensions best scaled by DME include overall speech severity, articulatory imprecision, reduced loudness, and short rushes of speech. Monotony was the only feature found to be a metathetic dimension and would be best scaled using EAI or DME. Findings call for rethinking the widespread use of EAI scales for rating perceptual features as part of the assessment and treatment of motor speech disorders.
OBJECTIVES: In Mayotte, cervical cancer represents the second cause of cancer mortality in women. Vaccination coverage against papillomavirus and screening rates are difficult to quantify but among the lowest in France. Added to this is an under-calibrated health system, which does not allow optimal treatment of cancers on site. The objective of the study was to study the elements that would increase papillomavirus vaccination among general practitioners.
METHODS: We carried out a qualitative study of phenomenological inspiration using semi-directed open interviews. The target population was private general practitioners based in Mayotte. The analysis was done by coding verbatim statements, from which emerged general themes, to build a model.
RESULTS: Twenty-two interviews were conducted. Vaccination was part of a context and was organized around the trio doctor-patient-institutions. The main pillar to vaccination was information, which could concern doctors or patients. The information delivered to patients through the media, campaigns in schools, and vaccination obligation were the main elements. The study revealed positive emotional dynamics of on-site HPV vaccination.
CONCLUSION: This study made it possible to better understand the ecosystem in which papillomavirus vaccination takes place in Mayotte, and to identify elements of vaccination promotion. Vaccination school campaigns should keep going on to increase vaccination uptake.
PURPOSE: Due to the indistinguishable clinical features of corticobasal syndrome (CBS), the antemortem differentiation between corticobasal degeneration (CBD) and its mimics remains challenging. However, the utility of conventional magnetic resonance imaging (MRI) for the diagnosis of CBD has not been sufficiently evaluated. This study aimed to investigate the diagnostic performance of conventional MRI findings in differentiating pathologically confirmed CBD from its mimics.
METHODS: Semiquantitative visual rating scales were employed to assess the degree and distribution of atrophy and asymmetry on conventional T1-weighted and T2-weighted images. Additionally, subcortical white matter hyperintensity (SWMH) on fluid-attenuated inversion recovery images were visually evaluated.
RESULTS: In addition to 19 patients with CBD, 16 with CBD mimics (progressive supranuclear palsy (PSP): 9, Alzheimer's disease (AD): 4, dementia with Lewy bodies (DLB): 1, frontotemporal lobar degeneration with TAR DNA-binding protein of 43 kDa(FTLD-TDP): 1, and globular glial tauopathy (GGT): 1) were investigated. Compared with the CBD group, the PSP-CBS subgroup showed severe midbrain atrophy without SWMH. The non-PSP-CBS subgroup, comprising patients with AD, DLB, FTLD-TDP, and GGT, showed severe temporal atrophy with widespread asymmetry, especially in the temporal lobes. In addition to over half of the patients with CBD, two with FTLD-TDP and GGT showed SWMH, respectively.
CONCLUSION: This study elucidates the distinct structural changes between the CBD and its mimics based on visual rating scales. The evaluation of atrophic distribution and SWMH may serve as imaging biomarkers of conventional MRI for detecting background pathologies.