anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Many developing countries lack access to recommended first-line treatments for metastatic renal cell carcinoma (mRCC), such as immune checkpoint inhibitors (ICIs) or ICI-tyrosine kinase inhibitor (TKI) combinations. As a result, predictive markers are necessary to identify patients who may benefit from single-agent TKIs for long-term response. This study aims to identify such parameters. This was a multi-centre, retrospective study of patients with mRCC who were undergoing first-line treatment with sunitinib or pazopanib. Patients who had been diagnosed with mRCC and had not experienced disease progression for 36 months or more were deemed to have achieved a long-term response. Predictive clinical and pathological characteristics of patients who did not experience long-term disease progression were investigated. A total of 320 patients from four hospitals were included in the study. The median age of the patients was 60 years (range 20-89 years). According to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk classification, 109 patients were classified as having favourable risk and 211 were in the intermediate-poor risk group. The median progression-free survival (PFS) and overall survival (OS) for all patients were 12.5 months and 76.4 months, respectively. In the long-term responder's group, the median PFS was 78.4 months. Among all patients, prior nephrectomy, the Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) <1, and the absence of brain metastasis were predictive factors for long-term response. For patients in the favourable risk group, the lack of brain metastasis was a predictor of long-term response. In the intermediate-poor risk group, prior nephrectomy and ECOG PS <1 were predictive factors for long-term response. Some individuals with mRCC may experience a durable response to TKIs. The likelihood of a long-term response can be determined by factors such as nephrectomy, ECOG PS < 1, and the absence of brain metastases.
NEW MATERIAL:The compound of formula I {A is H, group of formula II [R<1> is (substituted) 1-10C alkyl] or formula III (the symbol of formula IV represents that the bond takes E-configuration or Z-configuration or their arbitrary mixture based on the double bond)]; R is H or protecting group of protected OH}. EXAMPLE:2-Chloro-4-hydroxy-4-(3,4-dimethoxyphenylpropyl)-2-cyclo-pente none. USE:Medicinal drug. It exhibits strong activity to suppress the proliferation of cancer cell, has excellent carcinostatic effect and antiviral effect, etc., and is expected to be useful as a carcinostatic agent or antiviral agent. PREPARATION:The compound of formula I wherein A is H can be produced by oxidizing the cyclopentene alcohol compound of formula V with an oxidizing agent such as Jones reagent in a solvent preferably at >=-50 deg.C for 10min-1 day. When the group R of the resultant compound is protecting group of protected OH, the product can be converted to another compound of formula I wherein A is group of formula II by the aldol condensation with the aldehyde of formula VI.
Health technology assessment (HTA) decisions for pharmaceuticals are complex and evolving. New rare disease treatments are often approved more quickly through accelerated approval schemes, creating more uncertainties about clinical evidence and budget impact at the time of market entry. The use of real-world evidence (RWE), including early coverage with evidence development, has been suggested as a means to support HTA decisions for rare disease treatments. However, the collection and use of RWE poses substantial challenges. These challenges are compounded when considered in the context of treatments for rare diseases. In this paper, we describe the methodological challenges to developing and using prospective and retrospective RWE for HTA decisions, for rare diseases in particular. We focus attention on key elements of study design and analyses, including patient selection and recruitment, appropriate adjustment for confounding and other sources of bias, outcome selection, and data quality monitoring. We conclude by offering suggestions to help address some of the most vexing challenges. The role of RWE in coverage and pricing determination will grow. It is, therefore, necessary for researchers, manufacturers, HTA agencies, and payers to ensure that rigorous and appropriate scientific principles are followed when using RWE as part of decision-making.
Spinal cord injury (SCI) is a severe central nervous system disorder with no currently available effective treatment. Microglia are immune cells in the central nervous system that play crucial roles in the SCI occurrence, development, and recovery stages. They exhibit dynamic polarization over time and can switch between classical activation (M1) and alternative activation (M2) phenotypes to respond to environmental stimuli. The M1 phenotype is involved in initiating and sustaining inflammatory responses, while the M2 phenotype exerts anti-inflammatory effects and promotes tissue repair in damaged areas. Inhibiting M1 polarization and promoting M2 polarization have become hotspots in regulating neuroinflammation and treating SCI. This article provides a comprehensive review centered on modulating microglial polarization phenotypes for SCI treatment.
FIELD: organic chemistry. SUBSTANCE: synthesis is carried out by reaction of phenacyl bromide with 3-benzylamino-4-hydroxy-N-benzylbutaneamides in the mixture of ethylacetate and chloroform. Yield is 57%, m. p. is 82-84 C, empirical formula is CHBrNO, effective dose is 10 mg/kg, duration effect is a longer time by 3.84-3.38 and 2.84-2.34 times as compared with that of novocaine and trimecaine, respectively (2% solution of anesthetizing agent is used), toxicity LD290 against 154 mg/kg for novocaineamide. Anesthetizing effect of new agent is a longer time by 3.49-2.36 times as compared with that of novocaineamide. EFFECT: enhanced anesthetizing activity of synthesized compound. 7 tbl
Glioblastoma (GBM) is the most aggressive form of glioma, characterized by high mortality and poor prognosis. Dysregulation of microRNAs (miRNAs) plays a critical role in the progression and metastasis of GBM. This study aimed to investigate the role and molecular mechanism of miR-124-3p in GBM. Levels of miR-124-3p, EPHA2, and ALKBH5 were measured using quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, migration, invasion, and stemness were assessed using the Cell Counting Kit-8 (CCK-8), colony formation, Transwell, and sphere formation assays, respectively. Bioinformatics prediction, dual-luciferase reporter assays, and RNA pull-down experiments were employed to validate the target of miR-124-3p. RNA binding protein immunoprecipitation (RIP) and methylated RNA immunoprecipitation (Me-RIP) were utilized to evaluate the regulation of miR-124-3p maturation by ALKBH5. The results indicated that overexpression of miR-124-3p inhibited the proliferation, migration, invasion, and stemness of GBM cells. EPHA2 was identified as a direct downstream target of miR-124-3p, and its overexpression reversed the inhibitory effects of miR-124-3p on cellular functions. Furthermore, miR-124-3p targeted EPHA2 to inactivate the Wnt/β-catenin pathway. Additionally, ALKBH5 negatively regulated miR-124-3p by impeding its processing. In conclusion, knockdown of ALKBH5 promoted the processing of pri-miR-124-3p, increasing mature miR-124-3p levels, which inhibited the malignant behaviors of GBM cells by targeting EPHA2. These findings highlight the importance of the ALKBH5/miR-124-3p/EPHA2 axis in GBM.
Participants with a first-time ACL tear followed by reconstruction surgery randomized to the SOAR program group will complete a 6-month SOAR program (one-time Knee Camp, weekly home-based exercise therapy and physical activity with tracking, weekly 1:1 physiotherapist counseling sessions, and optional weekly group-based exercise classes) Consented trained physiotherapists will deliver the SOAR program throughout the study period to one or more SOAR program participants. Physiotherapists and SOAR participants will be randomly paired.
Cystic echinococcosis is caused by the tissue-dwelling larva (hydatid) of Echinococcus granulosus sensu lato. A salient feature is that this larva is protected by the acellular laminated layer (LL). As the parasite grows, the LL sheds abundant particles that can accumulate in the parasite's vicinity. The potential of LL particles to induce inflammation in vivo has not been specifically analysed. It is not known how each of its two major components, namely highly glycosylated mucins and calcium inositol hexakisphosphate (InsP6) deposits, impacts inflammation induced by the LL as a whole. In this work, we show that LL particles injected intraperitoneally cause infiltration of eosinophils, neutrophils and monocytes/macrophages as well as the disappearance of resident (large peritoneal) macrophages. Strikingly, the absence of calcium InsP6 enhanced the recruitment of all the inflammatory cell types analysed. In contrast, oxidation of the mucin carbohydrates caused decreased recruitment of neutrophils. The carbohydrate-oxidised particles caused cell influx nonetheless, which may be explained by possible receptor-independent effects of LL particles on innate immune cells, as suggested by previous works from our group. In summary, LL particles can induce acute inflammatory cell recruitment partly dependent on its mucin glycans, and this recruitment is attenuated by the calcium InsP6 component.
Technology is disclosed for monitoring a user's respiratory condition and provide decision support by analyzing a user's audio data. Spoken phonemes may be detected within audio data, and acoustic features may be extracted for the phonemes. A distance metric may be computed to compare phoneme feature sets of a user. Based on the comparison, a determination about the user's respiratory condition, such as whether the user has a respiratory condition (e.g., an infection) and/or whether the condition is changing, may be made. Some aspects include predicting the user's respiratory condition in the future utilizing the phoneme feature sets. Decision support tools in the form of computer applications or services may utilize the detected or predicted respiratory condition information to initiate an action for treating a current condition or mitigating a future risk.
Cardiometabolic risk factors are strongly influenced by lifestyle-related environmental factors including the consumption of an unhealthy Western diet (WD). Added sugars (i.e., caloric sweeteners added to food during processing or preparation) have become a major component of the WD that are especially high in added fructose. Americans currently consume more calories from added sugars than is recommended by the American Heart Association (AHA), leading to an increased risk of cardiovascular disease (CVD), which in turn shares common risk factors with age-related memory loss and dementia. Whereas glucose is used as an immediate energy source or stored as glycogen, fructose is associated with the delayed production of triglycerides (TGs) and uric acid. Previous studies have shown that a single high-sugar meal can increase TGs in the blood 150-180 minutes after meal consumption. Increased blood TGs promote release of harmful substances that contribute to the reduction in blood vessel function and may also impact brain blood vessel function; however, these effects are not well established in humans. Our preliminary data has shown a positive association between high added sugars and plasma TG and uric acid concentration, which has been associated with reduced blood vessel function. However, the direct effects of acute added sugar intake on brain blood vessel function is currently unknown. We have also observed that high blood TGs are associated with reduced microstructural integrity of the hippocampus, a brain structure important for memory and other thinking abilities. Therefore, the purpose of this study is to establish a causal link between high added sugar consumption and reduced brain blood vessel function and microstructural integrity. We propose to examine the acute effects of high TGs and uric acid from a single high-sugar meal on brain blood vessel function and brain integrity. To test this hypothesis, we will conduct a randomized-controlled crossover trial of a high-sugar meal vs. a low-sugar meal. This project has the potential to identify future risk of dementia and other memory-related brain diseases caused from repetitive acute insults from high added sugar consumption and will help us inform the public to make better dietary choices.
BACKGROUND: The diagnostic criteria for lateral lymph node metastasis in rectal cancer have not been established. This research aimed to investigate the risk factors for lateral lymph node metastasis and develop machine learning models combining these risk factors to improve the diagnostic performance of standard imaging.
METHOD: This multicentre prospective study included patients who underwent lateral lymph node dissection without preoperative treatment for rectal cancer between 2017 and 2019 in 15 Japanese institutions. First, preoperative clinicopathological factors and magnetic resonance imaging findings were evaluated using multivariable analyses for their correlation with lateral lymph node metastasis. Next, machine learning diagnostic models for lateral lymph node metastasis were developed combining these risk factors. The models were tested in a training set and in an internal validation cohort and their diagnostic performance was tested using receiver operating characteristic curve analyses.
RESULTS: Of 212 rectal cancers, 122 patients were selected, including 232 lateral pelvic sides, 30 sides of which had pathological lateral lymph node metastasis. Multivariable analysis revealed that poorly differentiated/mucinous adenocarcinoma, extramural vascular invasion, tumour deposit and a short-axis diameter of lateral lymph node ≥ 6.0 mm were independent risk factors for lateral lymph node metastasis. Patients were randomly divided into a training cohort (139 sides) and a test cohort (93 sides) and machine learning models were computed on the basis of a combination of significant features (including: histological type, extramural vascular invasion, tumour deposit, short- and long-axis diameter of lateral lymph node, body mass index, serum carcinoembryonic antigen level, cT, cN, cM, irregular border and mixed signal intensity). The top three models with the highest sensitivity in the training cohort were as follows: support vector machine (sensitivity, 1.000; specificity, 0.773), light gradient boosting machine (sensitivity, 0.950; specificity, 0.918) and ensemble learning (sensitivity, 0.950; specificity, 0.917). The diagnostic performances of these models in the test cohort were as follows: support vector machine (sensitivity, 0.750; specificity, 0.667), light gradient boosting machine (sensitivity, 0.500; specificity, 0.852) and ensemble learning (sensitivity, 0.667; specificity, 0.864).
CONCLUSION: Machine learning models combining multiple risk factors can contribute to improving diagnostic performance of lateral lymph node metastasis.
Subjects will receive single dose of midazolam on Day 1 followed by wash-out period of one day. Further the subjects will be administered placebo on Day 3 of single dose period followed by a wash-out period of 1 week. The subjects will then be administered a single dose of placebo for 28 days (Day 1 to Day 28 of repeat dosing period) and a single dose of midazolam on Day 29 of repeat dosing period.
The invention provides a pyridino-pyrazolon derivative and application thereof in a medicine against influenza a virus. The pyridino-pyrazolon derivative is provided and named a compound J1. A series of studies find that the compound J1 has remarkable activity of broad spectrum against influenza a virus. The compound J1 without toxic concentration is selected to conduct subtype pseudovirus experiments on H5N1 and H7N9. The result shows that the compound J1 has remarkable activity on inhibiting entry of the influenza a virus and present a dose-dependent manner. The study on the mechanism of action shows that the compound J1 targets at influenza virus hemagglutinin HA2 subunit, and inhibits membrane fusion of the influenza virus, so as to inhibits the entry of the influenza virus. The compound J1 can be applied to prepare medicines capable of preventing and treating influenza. Therefore, the compound J1 can be applied to prevention or treatment of the influenza a virus, and is expected to become a candidate medicine to prevent and treat the influenza for deep study and development.
An accelerated dose escalation scheme will be utilized initially with one patient enrolled per cohort. If at 10 mg or 20 mg dose level, any occurrence in cycle 1 of one ≥ Grade 2 adverse event related or possibly related to APG-1252 (graded as per the National Cancer Institute's Common Terminology Criteria for Adverse Events \[NCI CTCAE\] version 4.0) is the trigger for converting to a standard 3+3 design at that dose level.
Preoperative and intraoperative blood salvage autotransfusion is used in various surgical procedures. However, because of the risk of reinfusion of salvaged blood contaminated by tumor cells, the use of autotransfusion in hepatocellular carcinoma (HCC) patients undergoing liver resection is controversial. The critical points include whether tumor cells can be cleared by autotransfusion, whether autotransfusion increases the risk of recurrence or metastasis, and what are the indications for autotransfusion. Moreover, some other issues are still not addressed. For example, is it warranted to take the risk of tumor dissemination by using autotransfusion to avoid allogeneic blood transfusion? Do the remaining tumor cells after additional filtration by leukocyte depletion filters still possess potential tumorigenicity?
1350238 Cephalosporins R & L MOLECULAR RESEARCH Ltd 19 April 1971 [13 March 1970 19 June 1970(2) 19 Aug 1970 (3)] 24062/71 Headings C2A and C2C Novel cephalosporins having the Formula I wherein A is acetoxy or pyridinium and M is hydrogen, a non-toxic cation, or anionic charge when A is pyridinium, and non-toxic acidaddition salts thereof, are prepared by acylating a corresponding 7-aminocephalosporanic acid with an acid of Formula II wherein the amino group has a conventional protective group, or with an N-acylating derivative thereof, in an inert organic solvent at - 20‹ C. to + 70‹ C. and subsequently removing the amino protective group, and if desired when A is acetoxy, converting the acetoxy group to a pyridinium group by a conventional method. Such conversion may be effected by reacting the 3-acetoxymethyl compound with pyridine in aqueous medium or by reacting the said compound with thiopicolinic acid and reacting the product of formula with a mercuric perchlorate-pyridine complex which probably has the formula (p-Aminomethylphenylthio) acetic acid is prepared by the following procedure: ethylphenylthioacetate, paraformaldehyde, anhydrous ZnCl 2  and chloroform are saturated with dry HCl and the chloromethylation product is hydrolysed with water to give ethyl (p-chloromethylphenylthio) acetate. This ester is hydrolysed with acetic acid/HCl to (p-chloromethylphenylthio) acetic acid which is reacted with concentrated ammonium hydroxide to give the title acid. An alternative procedure consists of reacting (phenylthio) acetic acid with N-methylolohloroacetamide in the presence of C.H 2 SO 4 , treating the resulting N-methylolchloroacetamidophenyl compound with c. HCl to hydrolyse the amide linkage and give the hydrochloride salt of the (aminomethylphenylthio) acetic acid which is brought to pH5 to give (p-aminomethylphenylthio) acetic acid. The amino group of the aforesaid acid is protected with either a p-nitrocarbobenzoxy group using p-nitrobenzylchloroformate, or a p-tertbutoxycarbonyl group using tert.-butoxycarbonyl azide. (o-Aminomethylphenylthio) acetic acid is prepared by reducing thiosalicylic acid with LiAlH 4  to the corresponding alcohol, o-mercaptobenzyl alcohol, converting the latter to methyl (o-hydroxymethylphenylthio) acetate by reaction with methyl chloroacetate in methanolic sodium methoxide, reacting the hydroxy compound with SOCl 2  to give methyl (o-chloromethylphenylthio) acetate which is hydrolysed to (o-chloromethylphenylthio) acetic acid with acetic acid/ HCl, followed by treatment with NH 4 OH to give the desired o-aminomethyl compound. The amino group of this compound is protected as described above for the p-aminomethyl analogue. (m-Aminomethylphenylthio) acetic acid is prepared via a corresponding series of reactions and intermediates starting from m-mercaptobenzoic acid. The amino group is subsequently protected as a m-tert.-butoxycarbonylamino group, by reaction with the above-mentioned azide. The inventive cephalosporins (I) and their non-toxic salts may be formed into antibacterially active pharmaceutical compositions together with a pharmaceutical carrier or diluent.
COVID-19 vaccination side effects have been increasingly reported, including new-onset autoimmune diseases such as chronic arthritis, thrombocytopenia, Guillain-Barré syndrome (GBS), and more recently chronic inflammatory demyelinating polyneuropathies (CIDP). Molecular mimicry and vaccine adjuvants appear to be important contributors to immune-mediated neuropathies. However, whether the link between the COVID-19 vaccine and these autoimmune disorders is coincidental or causal remains uncertain. We describe the ever-reported case of acute-onset CIDP following the Oxford/AstraZeneca vaccine in Tunisia. The patient is a 41-year-old man who presented with acute, worsening weakness of the four limbs. The symptoms appeared 15 days after his first dose of the AstraZeneca vaccine. The diagnosis of GBS was initially confirmed according to the clinical features, the albumino-cytological dissociation in the cerebrospinal fluid (CSF), and the electroneuromyography (ENMG) findings. Serum workup for all known infections associated with immune-mediated neuropathy was negative. The patient was treated with plasma exchange without initial improvement followed by aggravation of the symptomatology after an interval of four and a half months. Control ENMG showed signs of CIDP meeting the European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) criteria of 2021. The patient was treated with maintenance intravenous immunoglobulin and oral corticosteroids. Neurological examination 3 months after discharge showed partial improvement. Worldwide, cases of demyelinating polyneuropathies post-COVID-19 vaccination are increasingly reported. The acute onset of CIDP might lead to a misdiagnosis of GBS. Awareness of this complication and distinction from GBS enables early relay with maintenance treatment to prevent relapses and severe complications. Post-COVID neuropathies are found to be more frequently linked to the AstraZeneca vaccine, however, temporal association does not confirm causal association.