anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The treatment of acute myeloid leukemia (AML) in older patients has not improved significantly in recent years when compared with the considerable progress that has been made in younger patients. Hence, new drugs and approaches are needed in this poor-prognosis group of patients with AML.

Nucleoside analogs are among the most active antileukemic agents available. Clofarabine was synthesized as a rational extension of the experience with other deoxyadenosine analogs. Clofarabine is converted to the monophosphate form by the enzyme deoxycytidine kinase which represents the major metabolite of clofarabine. Phosphorylation of clofarabine is substantially more efficient than that of other nucleosides such as fludarabine and so is intracellular retention of the triphosphate form of clofarabine. Mechanisms of action include inhibition of DNA synthesis, inhibition of DNA polymerases, and potent inhibition of ribonucleotide reductase (RNR) resulting in depletion of normal nucleotides and increased DNA uptake of the analog. Single agent clofarabine has shown activity in phase I studies in AML and ALL. As a potent inhibitor of RNR, however, clofarabine is ideal to be incorporated into biochemical modulation strategies such as have been tested and validated with fludarabine and ara-C in AML. By combining clofarabine with ara-C, inhibition of RNR by clofarabine will result in a drop of deoxynucleotides causing a decrease in the feedback inhibition of deoxycytidine kinase which is the rate-limiting step in the synthesis of ara-CTP leading to increased retention of ara-CTP. Therefore, the activity of clofarabine and ara-C in leukemic cells would be complemented by a biochemical synergism between these agents that should result in better clinical efficacy. We have established the safety of the combination in salvage patients with acute leukemias.
Two overnight sleep studies will be performed: a drug night and a placebo night. The patient will breath spontaneously (without CPAP) for both nights. On the study nights, subjects will present to the laboratory in the evening and be instrumented with a full polysomnigraphy for monitoring sleep, physiological variables (endotypes), and respiratory events. A history and physical examination will be performed on each night prior to beginning the study, as will a urine pregnancy test in premenopausal women. DAW2020 34 mg will be given 4 hours before lights out. Subjects will sleep at least 50% of the night in the supine position. At least four hours of sleep with high quality signal acquisition will be required for a study to be judged adequate. After the first overnight study is completed, there will be a one-week washout period prior to crossing over to the other treatment.
Pregnancy Category C. Because no adequate or well-controlled studies have been conducted in pregnant women, moxifloxacin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. 

Moxifloxacin was not teratogenic when administered to pregnant rats during organogenesis at oral doses as high as 500 mg/kg/day or 0.24 times the maximum recommended human dose based on systemic exposure (AUC), but decreased fetal body weights and slightly delayed fetal skeletal development (indicative of fetotoxicity) were observed. Intravenous administration of 80 mg/kg/day (approximately 2 times the maximum recommended human dose based on body surface area) to pregnant rats resulted in maternal toxicity and a marginal effect on fetal and placental weights and the appearance of the placenta. There was no evidence of teratogenicity at intravenous doses as high as 80 mg/kg/day. Intravenous administration of 20 mg/kg/day (approximately equal to the maximum recommended human oral dose based upon systemic exposure) to pregnant rabbits during organogenesis resulted in decreased fetal body weights and delayed fetal skeletal ossification. When rib and vertebral malformations were combined, there was an increased fetal and litter incidence of these effects. Signs of maternal toxicity in rabbits at this dose included mortality, abortions, marked reduction of food consumption, decreased water intake, body weight loss and hypoactivity. There was no evidence of teratogenicity when pregnant cynomolgus monkeys were given oral doses as high as 100 mg/kg/day (2.5 times the maximum recommended human dose based upon systemic exposure). An increased incidence of smaller fetuses was observed at 100 mg/kg/day. In an oral pre- and postnatal development study conducted in rats, effects observed at 500 mg/kg/day included slight increases in duration of pregnancy and prenatal loss, reduced pup birth weight and decreased neonatal survival. Treatment-related maternal mortality occurred during gestation at 500 mg/kg/day in this study.
Renal fibrosis is a crucial factor in the progression of chronic kidney diseases. Previous studies have suggested that apigenin (API) has potential in ameliorating renal fibrosis, but its therapeutic mechanism remains unclear. This study aims to elucidate the mechanisms by which API treats renal fibrosis using network pharmacology and experimental validation. Initially, we used the Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database and GeneCards database to identify molecular targets of API and associated genes. Next, we constructed a network of API-renal fibrosis targets, followed by protein-protein interaction (PPI) analysis. Subsequent analyses, such as Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, were performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). We also performed molecular docking studies to explore API's interactions with key proteins. To validate API's mechanism in treating renal fibrosis, we used a Human Kidney-2 (HK-2) cell model of epithelial-mesenchymal transition (EMT) induced by transforming growth factor-β1 (TGF-β1). We identified 77 API target genes, 8434 renal fibrosis target genes, and 64 intersection genes, which were primarily enriched in nuclear factor kappa-B (NF-κB) and Phosphatidylinositide 3-kinases/protein kinase B (PI3K-AKT) pathways. API significantly inhibited EMT in TGF-β1-induced HK-2 cells by regulating the expression of α-Smooth muscle actin (α-SMA) and E-cadherin and suppressing the protein expression of p-PI3K, p-AKT, and p-P65, which are related to the PI3K-AKT and NF-κB pathways. However, co-administration of the PI3K agonist 740Y-P counteracted API's inhibitory effects on these protein expressions. In summary, these findings highlight API's therapeutic potential in treating renal fibrosis by modulating EMT in renal tubular epithelial cells via the PI3K-AKT and NF-κB pathways.
Cancer has been identified by kidney transplant recipients as a critically important outcome. The co-occurrence of cancer and kidney transplantation represents a complex intersection of diseases, symptoms, and competing priorities for treatments. Research that focuses on biochemical parameters and clinical events may not capture the priorities of patients. Patient-centered research can improve the relevance and efficiency of research and is particularly pertinent in the setting of cancer and kidney transplantation to facilitate shared decision-making in complex clinical situations. In addition, patient-reported outcomes can facilitate the assessment of patients' experiences, symptom burden, treatment side effects, and quality of life. This review discusses patient-centered research in the context of kidney transplantation and cancer, including consumer involvement in research and patient-centered outcomes and their measures and inclusion in core outcome sets.
Tonsillectomy with or without adenoidectomy is a common surgical procedure in children and adolescents. Usually performed for recurrent tonsillitis or symptoms of airway obstruction, the procedure can result in significant post-operative pain. Common analgesic techniques include the use of oral acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen by mouth (PO) or ketorolac intravenous (IV), and narcotics. Acetaminophen has been shown to be effective in reducing pain and post-operative opioid requirements. Its administration can be oral, rectal, or intravenous. NSAIDs, though effective for pain control, have been shown to increase bleeding risk and disrupt hemostasis. Narcotics are effective for pain control but increase the risk of nausea and vomiting. They also have the potential to cause respiratory depression.

IV acetaminophen (OFIRMEV) is indicated for management of mild to moderate pain, and as an adjunct to opioids for severe pain. Several studies have examined the efficacy of IV acetaminophen vs placebo and/or active controls (meperidine, rectal acetaminophen (PR), tramadol). IV acetaminophen has been shown to be superior to placebo for pain control. Though there is data regarding peak plasma and Cerebral Spinal Fluid (CSF) concentration of acetaminophen when given by different routes (PO vs IV vs PR), there is no data comparing the efficacy of oral vs IV administration for pain control post-tonsillectomy in children.
###  Teratogenic effects

Pregnancy Category C: Fluconazole was administered orally to pregnant rabbits during organogenesis in two studies, at 5, 10 and 20 mg/kg and at 5, 25, and 75 mg/kg, respectively. Maternal weight gain was impaired at all dose levels, and abortions occurred at 75 mg/kg (approximately 20-60x the recommended human dose); no adverse fetal effects were detected. In several studies in which pregnant rats were treated orally with fluconazole during organogenesis, maternal weight gain was impaired and placental weights were increased at 25 mg/kg. There were no fetal effects at 5 or 10 mg/kg; increases in fetal anatomical variants (supernumerary ribs, renal pelvis dilation) and delays in ossification were observed at 25 and 50 mg/kg and higher doses. At doses ranging from 80 mg/kg (approximately 20-60x the recommended human dose) to 320 mg/kg embryolethality in rats was increased and fetal abnormalities included wavy ribs, cleft palate and abnormal cranio-facial ossification. These effects are consistent with the inhibition of estrogen synthesis in rats and may be a result of known effects of lowered estrogen on pregnancy, organogenesis and parturition. 

There are no adequate and well controlled studies in pregnant women. There have been reports of multiple congenital abnormalities in infants whose mothers were being treated for 3 or more months with high dose (400-800 mg/day) fluconazole therapy for coccidioidomycosis (an unindicated use). The relationship between fluconazole use and these events is unclear. Fluconazole should be used in pregnancy only if the potential benefit justifies the possible risk to the fetus.
Due to advances in medical treatment, most children with disabilities such as cerebral palsy or acquired brain injury can expect to live normal lifespans. As children, these individuals are cared for by expert healthcare providers working in coordinated teams in specialized pediatric settings. As these children reach adulthood, the availability of services and expertise drops dramatically because the adult health care system has not evolved to meet their specialized needs. In addition, transitioning from pediatric to adult services is often very difficult and stressful. Young people and their families must leave familiar healthcare settings and providers, and secure care in unfamiliar adult health care environments.

This proposed project will describe and evaluate the impact of a unique partnership model designed to coordinate transfer of care by formally linking pediatric and adult health care services. The LIFEspan model aims to (a) prepare youth and their families to adapt to adult healthcare provision, (b) provide a coordinated transfer process from pediatric to adult providers, and (c) establish sustainable access and appropriate adult care. The project will detail the specific service delivery that occurs with respect to preparation for transition and transfer of care in a process evaluation. An outcome evaluation will measure the effectiveness of the model in terms of its abilities to enable youth to maintain continuity within the health care system after transitioning from pediatric to adult care. Secondary outcomes, including how health, well-being, social participation, transition readiness, and health care utilization are affected by the LIFEspan model, will also be explored.
PURPOSE: A PEGylated exendin-4 dimer and a method for preparing the same are provided to enhance GLP-1 receptor binding affinity and to be used as a therapeutic agent for treating type 2 diabetes. CONSTITUTION: A PEGylated exendin-4 dimer is denoted by general formula 1. Polyethylene glycol or derivatives thereof is linear or branch type. A linker is bis-maleimide amine of chemical formula 2 containing two maleimide and one amine group. A method for preparing the dimer comprises: a step of adding polyethylene glycol or derivatives thereof and linker to a solvent to prepare a PEGylated linker; a step of reacting the PEGylated linker or recombinant excendin-4 in a reaction ratio of 1:2 to bind the exendin-4 dimer to the linker. The solvent contains dimethyl sulfoxide and dimethyl foramide. A pharmaceutical composition for preventing or treating type 2 diabetes contains the PEGylated excendin-4 dimer as an active ingredient.
PURPOSE OF REVIEW: Gastrointestinal (GI) dysfunction limits enteral nutrition (EN) delivery in critical illness and contributes to systemic inflammation. The enteroendocrine (EE) axis plays an integral role in this interface between nutrition, inflammation, and GI function in critical illness. In this review, we present an overview of the EE system with a focus on its role in GI inflammation and function.
RECENT FINDINGS: Enteroendocrine cells have been primarily described in their role in macronutrient digestion and absorption. Recent research has expanded on the diverse functions of EE cells including their ability to sense microbial peptides and metabolites and regulate immune function and inflammation. Therefore, EE cells may be both affected by and contribute to many pathophysiologic states and interventions of critical illness such as dysbiosis , inflammation, and alternative EN strategies. In this review, we present an overview of EE cells including their growing role in nonnutrient functions and integrate this understanding into relevant aspects of critical illness with a focus on EN.
SUMMARY: The EE system is key in maintaining GI homeostasis in critical illness, and how it is impacted and contributes to outcomes in the setting of dysbiosis , inflammation and different feeding strategies in critical illness should be considered.
Consistently high cholesterol or/and glucose level pose harmful threat to the body that may cause lethal health conditions (e.g. stroke, cardiovascular diseases). In addition, 3.6 million Malaysians are suffering from diabetes, the highest rate of incidence in Asia and one of the highest in the world. There is crucial need to find ways to improve the situation. Tele-health interventions and mindful eating behaviours are proposed to be effective in improving the levels of cholesterol and glucose. To investigate and explore the intervention, a small-scale randomised controlled trial will be conducted by comparing the effectiveness of mindful eating and the effect on cholesterol and glucose level. Students will collect and analyse both quantitative and qualitative data.

A small-scale randomised controlled trial will be conducted to compare the effectiveness of mindful eating and the effect on lipid level. Subjects will be randomly assigned to intervention or control group. For intervention group, subjects will be required to snap picture of every meal that they consume. At the end of the day, they are required to actively recall and reflect on how healthy they consider their meals to be. The reflection will be submitted to the research team daily together with the taken pictures of meal. As for the control group, subjects will only snap and submit the picture of their meals but without active recall and reflection.

Subjects are required to return to the community pharmacy after two months to follow-up on their glucose and lipid levels post intervention.
As in Western countries, familial pancreatic cancer accounts for 5-7% of pancreatic cancer (PC) in Japan. Opportunities for diagnosing hereditary pancreatic cancer (HPC) are increasing owing to the coverage of companion diagnostics and cancer genomic profiling by national health insurance in patients with unresectable or recurrent PC refractory to standard chemotherapies. HPC is recognized in 7% of PCs and 15% of familial pancreatic cancer, including germline variants of BRCA1/2, ATM, PALB2, APC, and mismatch repair genes. Individuals with 5-fold or greater inherited risks of PC are recommended to undergo pancreatic surveillance according to Japanese guidelines. The imaging modalities for this surveillance include endoscopic ultrasound, magnetic resonance cholangiopancreatography, abdominal ultrasound, and enhanced computed tomography. Currently, a nationwide prospective surveillance study is ongoing in Japan. Platinum-based chemotherapy is an effective pancreatic cancer treatment in patients with variants of homologous recombination repair genes (BRCA1/2 and PALB2); however, the use of platinum regimens solely based on familial/personal cancer history remains controversial. The efficacy of olaparib maintenance therapy, as confirmed by the POLO study, has significantly impacted the clinical treatment of advanced PC patients in Japan. Since the initiation of precision cancer medicine in 2019, genetic medicine for PC patients has expanded in Japan.
The objective of this study is to compare a minimal invasive approach with the conventional flexor carpi radialis approach for volar plating of distal radial fractures.

From January 2011 to September 2012, 157 patients with distal radial fractures were allocated into group A (n=83) and B (n=74). Patients in group A were treated through a 1.5 to 2-cm long incision, and patients in group B were treated through the conventional flexor carpi radialis approach. All fractures were fixed with volar plates. Patients were assessed range of motion of the wrist, grip strength of the hand, and pronation strength of the wrist. Results were analyzed with the Statistical Package for Social Sciences 13.0. A P \< 0.05 was statistically significant.
The present invention relates to a cosmetic container that enables the use of liquid cosmetics contained in a case as an applicator. The cosmetic container, according to the present invention, comprises: a case; a cap; and an applicator module. The case has an opening part at the top, and a sponge containing liquid cosmetics is located inside through the opening part. The cap is coupled to the top of the case and covers the opening part. The applicator module is installed in the cap and can be coupled and separated from the case via the cap. The applicator module comprises an applicator that accommodates and retains the cosmetics in the sponge by compressing the sponge by elastically moving up and down through the opening part while the cap is coupled to the case.
<P>PROBLEM TO BE SOLVED: To provide a mucosal immunopotentiator comprising an unconventional slightly digestible saccharide as an active ingredient.  <P>SOLUTION: The new mucosal immunopotentiator comprises a cyclofructan which is a cyclic inulooligosaccharide composed by binding fructose molecules into a cyclic form with β-2,1 bonds. The mucosal immunopotentiator has high general-purpose properties and widely applicable to objects of application to the oral cavity such as a food and drink or a medicine. When the mucosal immunopotentiator is ingested, the production of secretory type IgA is induced in the intestinal canal mucous membrane. Immunological functions of a biophylactic system can be maintained and improved by an increase in secretory type IgA content in feces. Thereby, the mucosal immunopotentiator can be connected to prophylaxis of various diseases such as infectious diseases, inflammatory bowel diseases or allergic diseases caused by lowering of mucosal immunological functions.  <P>COPYRIGHT: (C)2005,JPO&NCIPI
Several mechanisms, including altered local and systemic immune system, apoptosis, and new angiogenesis, are responsible for the development and progression of endometriosis. Over the years many markers have been studied, like CA 125 and, recently, neutrophil-to-lymphocyte ratio (NLR). This tool is cost-effectiveness and non-invasiveness as a marker of systemic inflammatory diseases. The aim of this study is to assess the role of NLR in the real-life management of patients with endometriosis in order to evaluate the possible association between this value and symptoms. We performed a retrospective analysis of 199 premenopausal women affected by endometriosis, from January 2013 to December 2020, evaluating the characteristics of disease, the symptoms and the NLR. Analyzing the neutrophiles, the mean ± SD value was 6.1 ± 4.5 × 103/ul, while for lymphocytes mean ± SD value was 1.8 ± 0.7.NLR was categorized according to its median value (> 2.62 vs ≤ 2.62). The comparison between NLR values and CA 125, endometriosis stage, dysmenorrhea and presence of chronic pelvic pain, adjusting for previous therapy did not find a significant association. An interesting result, although not significant, was the association between NLR and chronic pelvic pain (OR = 1.9). In the sub-group of patients without previous therapy this association is even stronger (OR = 4.8, 95% CI 0.5-50.2, p = 0.190). The link between NLR and chronic pelvic pain can provide a further hint to the clinician even when taking symptoms into account to develop a particular therapeutic treatment related to the various expressions of NLR. Finally, NLR may enable the creation of customized follow-up protocols that divide patients into high- and low-risk categories for endometriosis recurrence.
###  Risk Summary

There are no available data with Ryzumvi administration in pregnant women to inform a drug-associated risk. In animal toxicology studies, when phentolamine was administered orally to pregnant mice and rats during the period of organogenesis, skeletal immaturity and decreased growth was observed in the offspring at doses at least 24-times the recommended clinical dose. Additionally, a lower rate of implantation was seen in pregnant rats treated with phentolamine administered at least 60-times the recommended clinical dose. No malformations or embryofetal deaths were observed in the offspring of pregnant mice, rats, and rabbits administered phentolamine during the period of organogenesis at doses of at least 24-, 60-, and 20-times, respectively, the recommended clinical dose (see Data). Ryzumvi should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus.

###  Data

#### Animal Data 

Oral administration of phentolamine to pregnant rats and mice at doses at least 24-times the recommended clinical dose (based on a body weight per surface area (mg/m2) comparison with a 60-kg human) resulted in slightly decreased growth and slight skeletal immaturity of the fetuses. Immaturity was manifested by increased incidence of incomplete or unossified calcanei and phalangeal nuclei of the hind limb and of incompletely ossified sternebrae. At oral phentolamine doses at least 60-times the recommended clinical dose (based on a mg/m2 comparison with a 60-kg human), a slightly lower rate of implantation was found in rats. Phentolamine did not affect embryonic or fetal development in rabbits at oral doses at least 20-times the recommended dose (based on a mg/m2 comparison with a 60-kg human). No malformations or embryofetal deaths were observed in the rat, mouse or rabbit studies.