anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Despite treatment of locally advanced rectal cancer relapses are frequent. Several attempts to improve these results with therapy intensification have shown modest effect on disease free survival (DFS) and overall survival (OS). Recent studies with addition of sorafenib and cediranib revealed promising effect on tumor response with acceptable toxicity. Regorafenib is a multi tyrosine kinase inhibitor (TKI) with a broad mechanism of action. Therefore this trial investigates if similar results can be achieved as with sorafenib or cediranib.

The objective of the dose escalation part is to determinate safety, tolerability and the recommended dose. The objective of the expansion cohort is to assess the efficacy and to further characterize safety and tolerability of the therapy.
BACKGROUND: Hepatic fibrosis is a progressive disease, which is reversible in the early stages. The current monitoring methods have notable limitations that pose a challenge to early detection. In this study, we evaluated the utility of [18F]AlF-ND-bisFAPI positron emission tomography imaging of fibroblast activation protein (FAP) to monitor the progression of liver fibrosis.
METHODS: Two mouse models of liver fibrosis were established by bile duct ligation and carbon tetrachloride administration, respectively. Positron emission tomography imaging was performed with the FAP-specific radiotracer [18F]AlF-ND-bisFAPI for the evaluation of rat HSCs and mouse models of fibrosis and combined with histopathology, immunohistochemical staining, and immunoblotting to elucidate the relationships among radioactivity uptake, FAP levels, and liver fibrosis progression. Furthermore, [18F]AlF-ND-bisFAPI autoradiography was performed to assess tracer binding in liver sections from patients with varying degrees of liver fibrosis.
RESULTS: Cell experiments demonstrated that [18F]AlF-ND-bisFAPI uptake was specific in activated HSCs. Compared with control mice, [18F]AlF-ND-bisFAPI uptake in livers increased in the early stages of fibrosis and increased significantly further with disease progression. Immunohistochemistry and western blot analyses demonstrated that FAP expression increased with fibrosis severity. In accordance with the findings in animal models, ex vivo autoradiography on human fibrotic liver sections showed that radioactivity increased as fibrosis progressed from mild to severe.
CONCLUSIONS: [18F]AlF-ND-bisFAPI positron emission tomography imaging is a promising noninvasive method for monitoring the progression of liver fibrosis.
Eszopiclone is metabolized by CYP3A4 and CYP2E1 via demethylation and oxidation. There were no pharmacokinetic or pharmacodynamic interactions between eszopiclone and paroxetine, digoxin, or warfarin. When eszopiclone was coadministered with olanzapine, no pharmacokinetic interaction was detected in levels of eszopiclone or olanzapine, but a pharmacodynamic interaction was seen on a measure of psychomotor function. Eszopiclone and lorazepam decreased each other's Cmax by 22%. Coadministration of eszopiclone 3 mg to subjects receiving ketoconazole 400 mg, a potent inhibitor of CYP3A4, resulted in a 2.2-fold increase in exposure to eszopiclone. LUNESTA would not be expected to alter the clearance of drugs metabolized by common CYP450 enzymes. (See PRECAUTIONS.)
Vitamin B12 may be isolated from a streptomycin fermentation and purified by addition of an extract of Castle's intrinsic factor, adding a water-miscible organic solvent until its concentration is 40-60 per cent and separating the precipitated complex.  Specified organic solvents are acetone, methyl ethyl ketone, ethyl, n-propyl, isopropyl and tert. - butyl alcohols The procedure is detailed in Example 5.  U.S.A. Specification 2,595,159 is referred to.ALSO:Hog stomach tissue is extracted with water or with water containing a minor proportion of a water-miscible organic solvent, separating the extract of Castle's intrinsic factor from the insoluble residue, mixing the extract with a B12 Vitamin, precipitating the concentrate by addition of a water-miscible organic solvent to a concentration of 40-60 per cent and separating the resultant precipitate.  The starting material may be fresh frozen whole stomach or stomach mucosa and it may be defatted, desiccated and ground prior to extraction. Specified organic solvents include acetone, methyl ethyl ketone, ethyl alcohol, tert.-butyl alcohol, n- and isopropyl alcohol, and these may be used in the initial extraction in concentrations up to 15 per cent.  The B12 Vitamin may be the pure crystalline material or a crude product such as that from a streptomyces griseus fermentation.  In the latter case the formation of the concentrate of the complex purifies the vitamin (see Group IV (b)).  In an example, fresh-frozen whole hog stomach is ground and extracted with aqueous acetone acidified to pH 5 with hydrochloric acid.  The extract is filtered through infusorial earth, and to the filtrate is added Vitamin B12.  The mixture is cooled to 0 DEG  C. and pre-cooled acetone added until the final concentration is 55 per cent.  The precipitate is centrifuged, suspended in water and lyophilized. U.S.A. Specification 2,595,159 is referred to.
Pelvic or acetabular fractures were caused by high energy trauma, which may lead to poor prognosis for the old. The patients over 60 years were included in this study. The surgical procedure was conducted in two weeks. The less invasive methods involved Stoppa approach and novel plate. The data including surgical time, blood loss and results of follow-up were recorded. The clinical results were compared with the patients treated using traditional methods. Thus, the clinical outcome of Pelvic or acetabular fractures in old man was assessed.
An intrathecal administration of preservative-free morphine 0.3 mg in 3 ml NS prepared in a sterile ampoules by a hospital pharmacy will be performed before induction of anaesthesia in a sitting position between L2 and L3 - L4/L5 vertebrae. Standard general anaesthesia will be performed. After surgery, the patients will have the possibility to use PCA device with morphine, bolus dose 1 mg, lock-out interval 5 min for 3 days at a surgical ICU.
Conventional exercises and core stabilization exercises will be performed with the telerehabilitation method for 8 weeks. Patients will be contacted via laptop, ipad and phones with cameras, microphones and internet connection. Exercise by telerehabilitation will be implemented with a live connection for the first 4 weeks. In the second 4 week periods, exercise videos will be given to the patients and it will be checked by phone. In addition to the exercises in the conventional exercise group, patients will perform pelvic tilt, lateral bridge, single leg bridge, plank, extremity exercises in the crawling position, abdominal crunch, oblique crunch, dead bug, superman exercise. Exercises will be applied 3 times a week.
PURPOSE: Although functional seizures can start at any age, little is known about the individuals for whom onset occurs after the age of 40. It has been proposed that health-related traumatic events are more relevant causal factors for people with 'later-onset functional seizures' than for those whose functional seizures begin earlier in life, however, the illness representations of people with later-onset functional seizures have not yet been investigated. This study aimed to understand the experiences and illness representations of people with later-onset functional seizures.
METHODS: This was a mixed-methods study. People with later-onset functional seizures were recruited via a neurologist's caseload and online membership-led organisations. Semi-structured interview transcripts were analysed using Template Analysis according to the Common-Sense Model (CSM). Self-report measures of demographic and clinical details were collected to characterise the sample and verify themes.
RESULTS: Eight people with later-onset functional seizures participated in the study. Illness representations relating to all domains of the CSM as well as an additional theme of 'Triggers' were identified. Functional seizures were characterised as a mysterious brain disorder analogous to a computer malfunction and involving involuntary movements associated with alterations in consciousness. Perceptions of duration were indefinite, and triggers were unknown or at the extremes of autonomic arousal. Half of the sample identified health-related events/trauma as causal. Opinions were divided on 'cumulative life stress' as a causal factor. Most perceived themselves to have limited or no control but having 'control' over seizures was conceptualised as different to reducing their likelihood, frequency, or impact. Later-onset functional seizures were viewed as being more detrimental for caring and financial responsibilities but to have advantages for acceptance.
CONCLUSIONS: This is the first study to assess the illness representations of people with later-onset functional seizures. Many themes were similar to those identified in samples including people with earlier-onset functional seizures. Health-related trauma or events were the most strongly endorsed perceived causal factor, but with the exception of 'consequences', all representations were characterised by uncertainty. Clinicians should hold in mind the interaction between life stage and the consequences of later-onset functional seizures.
An influential model of spatial attention postulates three main attention-orienting mechanisms: disengagement, shifting, and engagement. Early research linked disengagement deficits with superior parietal damage, regardless of hemisphere or presence of spatial neglect. Subsequent studies supported the involvement of more ventral parietal regions, especially in the right hemisphere, and linked spatial neglect to deficient disengagement from ipsilateral cues. However, previous lesion studies faced serious limitations, such as small sample sizes and the lack of brain-injured controls without neglect. Additionally, some studies employed symbolic cues or used long cue-target intervals, which may fail to reveal impaired disengagement. We here used a machine-learning approach to conduct lesion-symptom mapping (LSM) on 89 patients with focal cerebral lesions to the left (LH) or right (RH) cerebral hemisphere. A group of 54 healthy participants served as controls. The paradigm used to uncover disengagement deficits employed non-predictive cues presented in the visual periphery and at short cue-target intervals, targeting exogenous attention. The main factors of interest were group (healthy participants, LH, RH), target position (left, right hemifield) and cue validity (valid, invalid). LSM-analyses were performed on two indices: the validity effect, computed as the absolute difference between reaction times (RTs) following invalid compared to valid cues, and the disengagement deficit, determined by the difference between contralesional and ipsilesional validity effects. While LH patients showed general slowing of RTs to contralesional targets, only RH patients exhibited a disengagement deficit from ipsilesional cues. LSM associated the validity effect with a right lateral frontal cluster, which additionally affected subcortical white matter of the right arcuate fasciculus, the corticothalamic pathway, and the superior longitudinal fasciculus. In contrast, the disengagement deficit was related to damage involving the right temporoparietal junction. Thus, our results support the crucial role of right inferior parietal and posterior temporal regions for attentional disengagement, but also emphasize the importance of lateral frontal regions, for the reorienting of attention.
Insulin resistance, often accompanied by obesity, plays a major role in the development of type 2 diabetes. This phenomenon may be related with the fact that American adolescents are now becoming less physically active in early puberty, explaining the largely pubertal and post-pubertal onset of type 2 diabetes in adolescence. Although regular physical activity has been suggested to attenuate obesity and prevent type 2 diabetes in high-risk children and adolescents, the magnitude of exercise training-induced improvement in the risk factors for type 2 diabetes has been only recently studied in adults and studied very little in pediatric populations. It is clear that exercise, diet, and genetics all contribute to the development of type 2 diabetes in children. However, the few studies that have been done to dissect the relative contributions of these three risk factors have generally used only lipid profiles as the end point. There have been a number of recent advances in our understanding of the molecular basis of type 2 diabetes, particularly, with regards to insulin regulatory pathways modulated by exercise within muscle tissue.
Dependence, evidenced by precipitation of withdrawal effects following abrupt discontinuation of PARNATE has been reported. Reported withdrawal effects included delirium (even with low daily doses), restlessness, anxiety, confusion, hallucinations, headache, weakness, diarrhea, and/or rapid relapse into depression. Thrombocytopenia and liver enzyme increases have also been observed in association with PARNATE withdrawal from high doses [see Overdosage (10.1)]

Withdrawal effects have appeared within 1 to 3 days of discontinuation and have persisted for several weeks after discontinuation. The use of daily doses greater than recommended and longer duration of use appear to be associated with a higher risk of withdrawal effects.

Monitor for withdrawal effects for at least 1 week after discontinuation. Consider discontinuing PARNATE therapy by slow, gradual dose reduction [see Dosage and Administration (2.3)].
Eltrombopag does not stimulate platelet production in rats, mice, or dogs because of unique TPO receptor specificity. Data from these animals do not fully model effects in humans.

Eltrombopag was not carcinogenic in mice at doses up to 75 mg/kg/day or in rats at doses up to 40 mg/kg/day (exposures up to 4 times the human clinical exposure based on AUC in patients with ITP at 75 mg/day and 2 times the human clinical exposure based on AUC in patients with chronic hepatitis C at 100 mg/day).

Eltrombopag was not mutagenic or clastogenic in a bacterial mutation assay or in two in vivo assays in rats (micronucleus and unscheduled DNA synthesis, 10 times the human clinical exposure based on Cmax in patients with ITP at 75 mg/day and 7 times the human clinical exposure based on Cmax in patients with chronic hepatitis C at 100 mg/day). In the in vitro mouse lymphoma assay, eltrombopag was marginally positive (less than 3-fold increase in mutation frequency). 

Eltrombopag did not affect female fertility in rats at doses up to 20 mg/kg/day (2 times the human clinical exposure based on AUC in patients with ITP at 75 mg/day and similar to the human clinical exposure based on AUC in patients with chronic hepatitis C at 100 mg/day). Eltrombopag did not affect male fertility in rats at doses up to 40 mg/kg/day, the highest dose tested (3 times the human clinical exposure based on AUC in patients with ITP at 75 mg/day and 2 times the human clinical exposure based on AUC in patients with chronic hepatitis C at 100 mg/day).
INTRODUCTION: Cytokeratins (CKs) have been associated with precancerous and cancerous gastric lesions in patients with Helicobacter pylori-associated chronic gastritis, making them useful for diagnosing epithelial tumors.
METHODOLOGY: A retrospective study was conducted utilizing 200 formalin-fixed paraffin-embedded gastric biopsy samples collected from the lesser curvature of the stomach. Samples from the control group, patients with H. pylori infection, and patients with H. pylori-associated gastritis, with complete and incomplete intestinal metaplasia (IM) were immunostained. Monoclonal antibodies were utilized to determine the expression of CK7, CK20, and Ki-67.
RESULTS: Patients infected with H. pylori had strong CK20 expression on the surface, and weak CK7 expression on the surface and deep glands; while non-specific chronic gastritis patients had weak focal CK7 expression and strong CK20 expression. The normal gastric mucosa of patients in the control group had relatively weak CK7 expression, restricted to a few cells in the neck and deep glands. CK20 showed diffuse strong reactivity on the surface. On the other hand, patients with complete IM showed a CK7 staining pattern that was either negative or weakly focal on the surface and crypts associated with diffuse surface CK20 and focal crypt staining corresponding to gastric type IM. The Ki67 proliferating index was low (≤ 15%) in H. pylori infected patients, high (> 30%) in patients with incomplete IM, and intermediate (16-30%) in patients with complete IM.
CONCLUSIONS: These results indicate a significant link between the expressions of CK7/CK20 and Ki67 in patients afflicted with H. pylori and IM.
This study is a parallel-group, blinded (participants, evaluators, and statisticians), randomized controlled trial exploring the effectiveness of electroacupuncture combined with standard quadruple antiemetic drugs for breast cancer patients undergoing HEC. Both groups will receive Olanzapine, Neurokinin-1 receptor antagonists (NK-1RAs), serotonin receptor antagonists \[5HT3RA\], and dexamethasone at the start of HEC on Day 1. Electroacupuncture or sham acupuncture will be randomly administered to each group. Participants will document all instances of nausea and vomiting and note the use of rescue antiemetic medications. Blood samples will be collected and analyzed to investigate whether genetic polymorphisms can predict electroacupuncture outcomes in breast cancer patients undergoing HEC. Primary and secondary outcomes as well as adverse events will be assessed.
The present invention provides compounds, salts and hydrates of Formula I, wherein the variables Ar<sub>1</sub>R<sub>2</sub>, R<sub>3</sub>, R<sub>4</sub>, r, q, and t are defined herein. Certain compounds of Formula I described herein possess potent antiviral activity. The invention also provides compounds of Formula I that are potent and/ or selective inhibitors of Hepatitis C virus replication. Certain compounds described herein inhibit assembly of the HCV replication complex. The invention also provides pharmaceutical compositions containing one or more compounds of Formula I, or a salt, solvate, or acylated prodrug of such compounds, and one or more pharmaceutically acceptable carriers, excipients, or diluents. The invention further comprises methods of treating patients suffering from certain infectious diseases by administering to such patients an amount of a compound of Formula I effective to reduce signs or symptoms of the disease. These infectious diseases include viral infections, particularly HCV infections. The invention is particularly includes methods of treating human patients suffering from an infectious disease, but also encompasses methods of treating other animals, including livestock and domesticated companion animals, suffering from an infectious disease. Methods of treatment include administering a compound of Formula I as a single active agent or administering a compound of Formula I in combination with on or more other therapeutic agent.
This disclosure relates to the field of RNA to prevent or treat coronavirus infection. In particular, the present disclosure relates to methods and agents for vaccination against coronavirus infection and inducing effective coronavirus antigen-specific immune responses such as antibody and/or T cell responses. These methods and agents are, in particular, useful for the prevention or treatment of coronavirus infection. Administration of RNA disclosed herein to a subject can protect the subject against coronavirus infection. Specifically, in one embodiment, the present disclosure relates to methods comprising administering to a subject RNA encoding a peptide or protein comprising an epitope of SARS-CoV-2 spike protein (S protein) for inducing an immune response against coronavirus S protein, in particular S protein of SARS-CoV-2, in the subject, i.e., vaccine RNA encoding vaccine antigen. Administering to the subject RNA encoding vaccine antigen may provide (following expression of the RNA by appropriate target cells) vaccine antigen for inducing an immune response against vaccine antigen (and disease-associated antigen) in the subject. In December 2019, a pneumonia outbreak of unknown cause occurred in Wuhan, China and it became clear that a novel coronavirus (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2) was the underlying cause. The genetic sequence of SARS-CoV-2 became available to the WHO and public (MN908947.3) and the virus was categorized into the betacoronavirus subfamily. By sequence analysis, the phylogenetic tree revealed a closer relationship to severe acute respiratory syndrome (SARS) virus isolates than to another coronavirus infecting humans, namely the Middle East respiratory syndrome (MERS) virus. On February 2nd, a total of 14'557 cases were globally confirmed in 24 countries including Germany and a subsequent self-sustaining, human-to-human virus spread resulted in that SARS-CoV-2 became a global epidemic.
An array of chemical compounds can be produced by the electrostatic deposition of its components onto a substrate. The subunit building blocks are coupled to the chemical groups on the substrate to synthesize a complex compound. By localizing the electrostatic deposition, different building blocks can be coupled at different positions on the substrate. Thus, a diverse and addressable set of chemical compounds is produced on the substrate to form an array of chemical compounds, e.g., of biological polymers. One application of this concept is the production of an oligonucleotide array. Other concepts provided here can be used in combination with the electrostatic deposition method or with other chemical synthetic methods. The invention provides, in part, methods of dispensing the nucleic acid subunits as a dry composition ( e.g., a particulate composition) that can be triboelectrically charged for the in-situ synthesis of nucleic acid polymers.
The invention discloses a Chinese herbal medicinal preparation for treating gingivitis. The Chinese herbal medicinal preparation comprises the following medicaments of: by weight, 20-30 parts of coptis; 20-30 parts of rehmanniae radix; 12-18 parts of Mussaenda; 12-18 parts of Abelmosehus moschatus; 12-18 parts of Teloshistaceae; 18-24 parts of solanum nigrum; 18-24 parts of Jinhuabi; 12-18 parts of Galium tricorne; 12-18 parts of india skullcap; 18-24 parts of gypsophila paniculata; 18-24 parts of Cortex moutan; 6-12 parts of Asarum Herb; 18-24 parts of gypsum; 18-24 parts of Amaranthus spinosus; 24-36 parts of cimicifuga foetida; and 12-18 parts of Chenopodium ambrosioides L. According to the formula, cuttlebone, fructuslitseae and Boltonia indica(L)Bentb. are used as monarch drugs; corydalis tuber, Chinese pholidota herb, Eclipta prostrata L and red bayberry are used as ministerial drugs; Amaranthus spinosus, Cudrania cochinchinensis (Lour.) Kudo et Masam. and sweet potato are used as adjuvant drugs; and Berchemia lineata DC., Zanthoxylum nitidum and red bayberry are used as conductant drugs. The oral aqua medicine has advantages of simple production, simple operation technology, abundant drug resources and low production cost, is convenient for patients to take and is safe to use, and has no side-effect.
Patients in this arm will be administered Nelarabine 325 mg/m2 (50% of single agent MTD) and 330 mg/2 Cyclophosphamide. Patients will only enter this arm if the MTD at Dose Level 1 has been exceeded. If the MTD is exceeded at Dose Level 0, the study will be closed.
The mHNMT for Tinnitus program was modified based on participant feedback of the original HNMT. This study will include 6 sessions, 2 sessions a week including the following interventions: resonance training, music relaxation, Intonation Training and session review/homework.