anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Participants with solid tumors for whom no effective standard therapy exists will be included in this Part. Dose escalation of M1231 will be administered as single agent.
PURPOSE: A dental composite resin block is provided to manufacture a large block for indirect restoration. CONSTITUTION: A dental composite resin block is able to obtain a large block for indirect restoration and a plurality of restorations by processing once. The composite resin block contains monomers and/or oligomers with unsaturated double bond, a polymerization initiator for starting polymerization, and a filler. The size of the particles for the resin composition is 0.3-3 um. The monomer containing the unsaturated double bond is a methyl methacrylate(MMA) monomers. The monomers are a mixture of 2,2-bis-(4-(2-hydroxy-3-methacyloyloxypropoxy)phenyl)propane(Bis-GMA) and triethyelne glycol dimethacrylate(TEGDMA). The polymerization initiator contains photoplymerizatioin initiator and/or thermal polymerization initiator. The filler contains an inorganic filler and/or organic filler.
A 2-year carcinogenicity study was conducted in F-344 rats, and a 78-week carcinogenicity study was conducted in CD-1 mice. In the 104-week oral carcinogenicity study in rats, sapropterin dihydrochloride doses of 25, 80, and 250 mg/kg per day (0.2, 0.7, and 2 times the maximum recommended human dose of 20 mg/kg per day, respectively, based on body surface area) were used. In the 78-week oral carcinogenicity study in mice, sapropterin dihydrochloride doses of 25, 80, and 250 mg/kg per day (0.1, 0.3, and 2 times the recommended human dose, respectively, based on body surface area) were used. In the 2-year rat carcinogenicity study, there was a statistically significant increase in the incidence of benign adrenal pheochromocytoma in male rats treated with the 250 mg/kg per day (about 2 times the maximum recommended human dose, based on body surface area) dose, as compared to vehicle treated rats. The mouse carcinogenicity study showed no evidence of a carcinogenic effect, but the study was not ideal due to its duration of 78 instead of 104 weeks. 

Sapropterin dihydrochloride was genotoxic in the in vitro Ames test at concentrations of 625 mcg (TA98) and 5,000 mcg (TA100) per plate, without metabolic activation. However, no genotoxicity was observed in the in vitro Ames test with metabolic activation. Sapropterin dihydrochloride was genotoxic in the in vitro chromosomal aberration assay in Chinese hamster lung cells at concentrations of 0.25 and 0.5 mM. Sapropterin dihydrochloride was not mutagenic in the in vivo micronucleus assay in mice at doses up to 2,000 mg/kg per day (about 8 times the maximum recommended human dose of 20 mg/kg per day, based on body surface area). Sapropterin dihydrochloride, at oral doses up to 400 mg/kg per day (about 3 times the maximum recommended human dose, based on body surface area) was found to have no effect on fertility and reproductive function of male and female rats.
Myocardial infarction (MI) is a major cause of morbidity and mortality worldwide. Although clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) gene editing holds immense potential for genetic manipulation, its clinical application is hindered by the absence of an efficient heart-targeted drug delivery system. Herein, we developed CRISPR-Cas9 ribonucleoprotein (RNP)-loaded extracellular vesicles (EVs) conjugated with cardiac-targeting peptide (T) for precise cardiac-specific genome editing. RNP complexes containing Cas9 and single guide RNA targeting miR-34a, an MI-associated molecular target, were loaded into EVs (EV@RNP). Gene editing by EV@RNP attenuated hydrogen peroxide-induced apoptosis in cardiomyocytes via miR-34a inhibition, evidenced by increased B-cell lymphoma 2 levels, decreased Bcl-2-associated X protein levels, and the cleavage of caspase-3. Additionally, to improve cardiac targeting in vivo, we used click chemistry to form functional T-EV@RNP by conjugating T peptides to EV@RNP. Consequently, T-EV@RNP-mediated miR-34a genome editing might exert a protective effect against MI, reducing apoptosis, ameliorating MI injury, and facilitating the recovery of cardiac function. In conclusion, the genome editing delivery system established by loading CRISPR/Cas9 RNP with cardiac-targeting EVs is a powerful approach for precise and tissue-specific gene therapy for cardiovascular disease.
Obesity is becoming a global health problem. Visceral adiposity is the main cause of metabolic and cardiovascular diseases. Dietary improvement is the key to controlling obesity. We hypothesized that a higher Composite Dietary Antioxidant Index (CDAI) was associated with a lower visceral adipose tissue (VAT) area. In this cross-sectional study, 10,389 adults were selected from the National Health and Nutrition Examination Survey 2011-2018. CDAI was calculated based on 6 micronutrients: zinc, selenium, total carotenoids, vitamin A, vitamin C, and vitamin E. VAT area was determined by the dual-energy X-ray absorptiometry scan. Linear regression models were constructed to evaluate the association between CDAI and VAT area. Subgroup analyses were also performed. The mean age of participants was 39.68 years, 5240 were male, and 3841 of those were non-Hispanic White. The inverse associations were observed in all models. In model 3, CDAI was inversely associated with VAT area as a continuous variable, β (95% confidence interval), -0.56 (-0.85 to -0.27). When compared with the first tertile, the third tertile of CDAI was also inversely associated with VAT area, β (95% confidence interval), -6.72 (-10.44 to -2.99). No interactions were found in the subgroup analyses. In conclusion, an inverse association between CDAI and VAT area was found among U.S. adults aged 20 to 59 years. These results suggest the possible benefit of an antioxidant diet in relieving visceral obesity. More prospective studies are needed to identify this dietary benefit.
A method, non-transitory computer readable medium, and pharmaceutical assessment computing device that effectively assesses pharmaceutical data. With this technology pharmaceutical data for a candidate drug is obtained. The pharmaceutical data including a drug indication and a pharmaceutical value for a plurality of pharmaceutical parameters. Next, standard of care data including standard of care values corresponding to the obtained drug indication for the candidate drug is obtained and deviations between the pharmaceutical parameter values and the standard of care values is determined. A plurality of pharmaceutical assessment scores is assigned to each one of a plurality of pharmaceutical parameters based on the determined deviations. A target product profile for the candidate drag is provided based on the assigned plurality of pharmaceutical assessment scores.
Tourette's Syndrome (TS) is a neurodevelopmental disorder characterized by repetitive, involuntary movements and vocalizations known as tics. It typically manifests in childhood and may persist into adulthood. The prevalence of TS varies globally, affecting approximately 1% of the population. Males are more commonly affected than females, and there is a broad spectrum of symptom severity. Treatment-refractory Tourette's Syndrome (TR-TS) refers to cases where standard therapeutic interventions, such as behavioural therapy and medications, have shown limited effectiveness. TR-TS prevalence is relatively lower but highlights the challenges in managing severe and persistent symptoms. In a comprehensive survey of diverse neuromodulation therapies, targeting specific nuclei with DBS has the most potential for TR-TS with apparent symptoms. The stimulation targets of DBS for patients with obsessive-compulsive disorder include GPi, amGPi, pvGPi, Cm-Spv-Voi, Cm-Voi, and NA-ALIC. However, the DBS case reports are limited and lack high-quality, evidence-based medical evidence. So, this cohort study focuses on the effectiveness of DBS-targeted GPi, amGPi, pvGPi, Cm-Spv-Voi, Cm-Voi, NA-ALIC, or other unreported nuclei targets on TR-TS.

Another goal of this program is to study the neuronal activity of the GPi, amGPi, pvGPi, Cm-Spv-Voi, Cm-Voi, and NA-ALIC, or other unreported nuclei targets, respectively. At the same time, some subjects are presented with a task involving an unexpected reward. This separate study is an option and will not affect current study participation.

Some participants will also be invited to join a related study that involves positron emission tomography (PET) scanning to determine how the stimulation changes activity in the brain. Participation in the separate PET study is optional and will not affect current study participation.
Age-related aneuploidy in human oocytes is a major factor contributing to decreased fertility and adverse reproductive outcomes. As females age, their oocytes are more prone to meiotic chromosome segregation errors, leading primarily to aneuploidy. Elevated aneuploidy rates have also been observed in oocytes from very young, prepubertal conceptions. A key barrier to developing effective treatments for age-related oocyte aneuploidy is our incomplete understanding of the molecular mechanisms involved. The challenge is becoming increasingly critical as more people choose to delay childbearing, a trend that has significant societal implications. In this review, we summarize current knowledge regarding the process of oocyte meiosis and folliculogenesis, highlighting the relationship between age and chromosomal aberrations in oocytes and embryos, and integrate proposed mechanisms of age-related meiotic disturbances across structural, protein, and genomic levels. Our goal is to spur new research directions and therapeutic avenues.
Exercise equivalent to the current exercise guidelines. In total 210 minutes per week of continuous moderate intensity (70% HRmax) exercise. Home based training.
The control group was treated with capecitabine at a conventional dose: 1,250 mg/m2 orally twice daily (once in the morning and once in the evening; equivalent to a total daily dose of 2,500 mg/m2). Treatment was given for 2 weeks, followed by a 1 week of discontinuation, with each cycle lasting 3 weeks, and there were a total of 4 cycles. Administration: Swallow the tablet whole with water 30 min after breakfast and dinner every day.
BACKGROUND: Several methods exist to reduce the number of arterial blood gases (ABGs). One method, Roche v-TAC, has been evaluated in different patient groups. This paper aggregates data from these studies, in different patient categories using common analysis criteria.
RESEARCH DESIGN AND METHODS: We included studies evaluating v-TAC based on paired arterial and peripheral venous blood samples. Bland-Altman analysis compared measured and calculated arterial values of pH, PCO2, and PO2. Subgroup analyses were performed for normal, chronic hypercapnia and chronic base excess, acute hyper- and hypocapnia, and acute and chronic base deficits.
RESULTS: 811 samples from 12 studies were included. Bias and limits of agreement for measured and calculated values: pH 0.001 (-0.029 to 0.031), PCO2 -0.08 (-0.65 to 0.49) kPa, and PO2 0.04 (-1.71 to 1.78) kPa, with similar values for all sub-group analyses.
CONCLUSION: These data suggest that v-TAC analysis may have a role in replacing ABGs, avoiding arterial puncture. Substantial data exist in patients with chronic hypercapnia and chronic base excess, acute hyper- and hypocapnia, and in patients with relatively normal acid-base status, with similar bias and precision across groups and across study data. Limited data exist for patients with acute and chronic base deficits.
The invention relates to the technical field of animal virology, epizootiology and genetic engineering, in particular to a synthesis method and application of an mMEP of a PRRSV (Porcine Reproductive and Respiratory Syndrome Virus) with high pathogenicity. The synthesis method is characterized in that the T-cell epitopes of the GP3, GP4, GP5, protein M and protein N of a PRRSVWUH3 strain are connected with the epitope of a modified GP5B cell through linkers; according to mammal codon preference, codons are modified to synthesize the mMEP artificially. The nucleotide sequence of the mMEP is shown in SEQ ID NO:1; the protein sequence of the mMEP is shown in SEQ ID NO:2. The synthetic mMEP is contained in an eukaryotic expression plasmid pcDNA3.1-mMEP. Escherichia coli DH5(Alpha)/pcDNA3.1-mMEP containing the eukaryotic expression plasmid pcDNA3.1-mMEP are preserved in China Center for Type Culture Collection (CCTCC), and the preservation number of the escherichia coli DH5(Alpha)/pcDNA3.1-mMEP is CCTCC NO: M 2012171. The invention further discloses application of the mMEP in preparing an PRRS DNA vaccine.
Disclosed herein is a vaccine which provides immunity to mammals from infection and/or disease caused by a lentivirus, such as equine infectious anemia virus, human immunodeficiency virus (HIV), feline immunodeficiency virus (FIV), bovine immunodeficiency virus (BIV) or simian immunodeficiency virus (SIV) said composition comprising a deletion in a gene that blocks replication of the virus in vivo. Said composition allows differentiation between vaccinated and non-vaccinated, but exposed, mammals and provides safety and immunity when administered as a vaccine to mammals. Preferably said composition encompasses at least one deletion in a lentivirus which allows mammals to be safely vaccinated and provides protection from exposure to wild-type lentiviruses. It also encompasses a marker vaccine in which a foreign gene is inserted into the gene-deleted region, said inserted gene providing a diagnostic tool for use in vaccinated mammals and, potentially, protection from infection from a foreign disease. The scope of the invention encompases an EIAV vaccine that allows equines to be safely vaccinated and protected from disease without converting to a seropositive status on the Coggin's Test or any other test which measures p26, said p26 antigen being expressed in disease-producing wild-type EIAVs. Additionally, said EIA vaccine virus cannot cause clinical disease in mammals or spread or shed to other mammals including equines. Finally, this invention encompasses a marker vaccine in which vaccinated equines can be distinguished from non-vaccinated equines by detection of a foreign gene in the vaccinated animals. A diagnostic test to detect this foreign gene or gene product is also described.
Providers who have contributed at least 25 Atrial Fibrillation patients to the Symphony pharmacy claims dataset will be contacted to participate. Interested providers will be consented using an online consent form and then will be asked to complete 1 survey that contains scenarios and ranking questions.
Patients will have a single blood draw for the analysis of antibodies induced by idursulfase. Samples will be used to further evaluate whether the antibodies induced by idursulfase bind to GSK2788723 molecules in vitro and if these antibodies neutralize the bioactivity of GSK2788723 in vitro.
OBJECTIVE: This study aims to evaluate the differences between The balloon catheter method and End-hole Catheter Method in measuring hepatic venous pressure gradient (HVPG) among cirrhosis patients.
METHODS: From October 2017 to January 2024, patients who underwent HVPG measurements using both methods were consecutively included. HVPGs obtained from both methods were compared with the portal vein pressure gradient (PPG) obtained via transjugular intrahepatic portosystemic shunt (TIPS) using paired comparisons. Additionally, the consistency and predictive ability for bleeding risk of the two methods, as well as the impact of intrahepatic veno-venous shunt (IHVS), were analyzed.
RESULTS: The study enrolled 145 patients, each of whom had HVPG measured by both methods. PPG was measured in 61 patients. There was a statistically significant difference between the PPGs and HVPGs measured by both the balloon catheter method and the end-hole catheter method (P < 0.001), with the HVPG mean values obtained by the end-hole catheter method being closer to the PPGs. In the non-IHVS group, no significant statistical difference was found between the two methods (P = 0.071). In contrast, the IHVS group showed a significant difference (P < 0.001), with a mean difference of 2.98 ± 4.03 mmHg. When IHVS was absent, the measurement results from the end-hole catheter method and the balloon catheter method were found to be highly correlated. The end-hole catheter method has a higher screening capability for patients at risk of bleeding compared to the balloon catheter method (75.90% vs. 72.86%).
CONCLUSION: HVPG measurements using either the balloon catheter method or end-hole catheter method showed significant difference with the PPG. The end-hole catheter method has a higher screening capability for patients at risk of bleeding, and IHVS could lead to lower HVPG measurements with The balloon catheter method.
BACKGROUND: Gastrodin (GAS), a main bioactive component of the herbal plant, Gastrodia elata Blume, has shown to have beneficial effects on neuroinflammatory diseases such as Alzheimer's disease in animal studies and migraine in clinical studies. Inflammasome is a multimeric protein complex having a core of pattern recognition receptor and has been implicated in the development of neuroinflammatory diseases. Gastrodin has shown to modulate the activation of nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome. This study investigated the effects of GAS on the intensity of mechanical allodynia and associated changes in NLRP3 inflammasome expression at the spinal level using L5/6 spinal nerve ligation model (SNL) in rats.
METHODS: Intrathecal (IT) catheter implantation and SNL were used for drug administration and pain model in male Sprague-Dawley rats. The effect of gastrodin or MCC950 (NLRP3 inflammasome inhibitor) on mechanical allodynia was measured by von Frey test. Changes in NLRP3 inflammasome components and interleukin-1β (IL-1β) and cellular expression were examined in the spinal cord and dorsal root ganglion.
RESULTS: The expression of NLRP3 inflammasome components was found mostly in the neurons in the spinal cord and dorsal root ganglion. The protein and mRNA levels of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, and IL-1β were upregulated in SNL animals compared to Sham animals. IT administration of GAS significantly attenuated the expression of NLRP3 inflammasome and the intensity of SNL-induced mechanical allodynia. NLRP3 inflammasome inhibitor, MCC950, also attenuated the intensity of allodynia, but the effect is less strong and shorter than that of GAS.
CONCLUSIONS: Expression of NLRP3 inflammasome and IL-1β is greatly increased and mostly found in the neurons at the spinal level in SNL model, and IT gastrodin exerts a significant anti-allodynic effect in SNL model partly through suppressing the expression of NLRP3 inflammasome.
Hepatic lipid metabolism is modulated by the circadian rhythm; therefore, circadian disruption may promote obesity and hepatic lipid accumulation. This study aims to investigate dietary pterostilbene (PSB) 's protective effect against high-fat-diet (HFD)-induced lipid accumulation exacerbated by chronic jet lag and the potential role of gut microbiota therein. Mice were treated with a HFD and chronic jet lag for 14 weeks. The experimental group was supplemented with 0.25% (w/w) PSB in its diet to evaluate whether PSB had a beneficial effect. Our study found that chronic jet lag exacerbates HFD-induced obesity and hepatic lipid accumulation, but these adverse effects were significantly mitigated by PSB supplementation. Specifically, PSB promoted hepatic lipolysis and β-oxidation by upregulating SIRT1 expression, which indirectly reduced oxidative stress caused by lipid accumulation. Additionally, the PSB-induced elevation of SIRT1 and SIRT3 expression helped prevent excessive autophagy and mitochondrial fission by activating Nrf2-mediated antioxidant enzymes. The result was evidenced by the use of SIRT1 and SIRT3 inhibitors in in vitro studies, which demonstrated that activation of SIRT1 and SIRT3 by PSB is crucial for the translocation of PGC-1α and Nrf2, respectively. Moreover, the analysis of gut microbiota suggested that PSB's beneficial effects were partly due to its positive modulation of gut microbial composition and functionality. The findings of this study suggest the potential of dietary PSB as a candidate to improve hepatic lipid metabolism via several mechanisms. It may be developed as a treatment adjuvant in the future.
BACKGROUND: Postoperative complications after colorectal cancer surgery have been linked to the gut microbiome. However, the impact of mechanical bowel preparation using oral preparation agents or rectal enema on postoperative infections remains poorly understood. This study aimed to compare the impact of oral preparation and rectal enema on the gut microbiome and postoperative complications.
METHODS: This open-label pilot RCT was conducted at the National Cancer Institute, Vilnius, Lithuania. Patients with left-side colorectal cancer scheduled for elective resection with primary anastomosis were randomized 1 : 1 to preoperative mechanical bowel preparation with either oral preparation or rectal enema. Stool samples were collected before surgery, and on postoperative day 6 and 30 for 16S rRNA gene sequencing analysis. The primary outcome was difference in β-diversity between groups on postoperative day 6.
RESULTS: Forty participants were randomized to oral preparation (20) or rectal enema (20). The two groups had similar changes in microbiome composition, and there was no difference in β-diversity on postoperative day 6. Postoperative infections occurred in 12 patients (32%), without differences between the study groups. Patients with infections had an increased abundance of bacteria from the Actinomycetaceae family, Actinomyces genus, Sutterella uncultured species, and Enterococcus faecalis species.
CONCLUSION: Mechanical bowel preparation with oral preparation or rectal enema resulted in similar dysbiosis. Patients who experienced postoperative infections exhibited distinct gut microbiome compositions on postoperative day 6, characterized by an increased abundance of bacteria from the Actinomycetaceae family, Actinomyces genus, Sutterella uncultured species, and Enterococcus faecalis species.
REGISTRATION NUMBER: NCT04013841 (http://www.clinicaltrials.gov).
Participants will be randomly assigned to one of eight study groups which will be one or a combination of 4 conditions: (1) in person individualized diet and exercise counseling (2) diet and exercise text messages (3) weekly telephone support and (4) self-monitoring tools for diet and weight. For the first part of the study, Survey, approximately 64 drivers and 36 management staff will take pate in the feedback questionnaire. For the second part of the study, Interview, approximately 8 drivers and 12 management staff may be invited to take part in an interview via phone, in person, or teleconference (Zoom).
Superficial cervical plexus block (SCP) block is given using high frequency linear ultrasound probe connected to an ultrasound machine to visualize superficial cervical plexus (SCP) posterior to the midpoint of sterno cleido mastoid (SCM) muscle. Once SCP is identified, a combination of 5 ml bupivacaine (0.5%) and 5 ml lidocaine (2%) is injected after negative aspiration followed by injection of 1 ml to confirm the area, using a 22 gauge B-bevel Echogenic Needle.
Patients in the control group receive azathioprine in combination with steroid therapy. The dosage of azathioprine (AZA) is adjusted based on the activity of thiopurine methyltransferase (TPMT), and TPMT activity should be measured before the administration of azathioprine. For individuals with normal TPMT activity, it is recommended to use AZA at a dosage of 2.0-3.0 mg·kg/d; for patients with TPMT enzyme mutations, it is recommended to use AZA at a dosage of 0.5-1.5 mg·kg/d. The initial treatment dose is suggested to be 50 mg AZA per day; the dose can be increased to the optimal dosage based on TPMT activity.