anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Risk Summary 

JANTOVEN is contraindicated in women who are pregnant except in pregnant women with mechanical heart valves, who are at high risk of thromboembolism, and for whom the benefits of JANTOVEN may outweigh the risks [see Warnings and Precautions (5.7)]. JANTOVEN can cause fetal harm. Exposure to warfarin during the first trimester of pregnancy caused a pattern of congenital malformations in about 5% of exposed offspring. Because these data were not collected in adequate and well-controlled studies, this incidence of major birth defects is not an adequate basis for comparison to the estimated incidences in the control group or the U.S. general population and may not reflect the incidences observed in practice. Consider the benefits and risks of JANTOVEN and possible risks to the fetus when prescribing JANTOVEN to a pregnant woman.

Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. 

Clinical Considerations 

Fetal/Neonatal Adverse Reactions 

In humans, warfarin crosses the placenta, and concentrations in fetal plasma approach the maternal values. Exposure to warfarin during the first trimester of pregnancy caused a pattern of congenital malformations in about 5% of exposed offspring. Warfarin embryopathy is characterized by nasal hypoplasia with or without stippled epiphyses (chondrodysplasia punctata) and growth retardation (including low birth weight). Central nervous system and eye abnormalities have also been reported, including dorsal midline dysplasia characterized by agenesis of the corpus callosum, Dandy-Walker malformation, midline cerebellar atrophy, and ventral midline dysplasia characterized by optic atrophy. Mental retardation, blindness, schizencephaly, microcephaly, hydrocephalus, and other adverse pregnancy outcomes have been reported following warfarin exposure during the second and third trimesters of pregnancy [see Contraindications (4)].
BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver malignancy. Although its incidence is lower than that of hepatocellular carcinoma (HCC), ICC has a worse prognosis, and it is more prone to recur and metastasize, resulting in a far greater level of malignancy.
METHODS: Bioinformatics analysis and qRT-PCR were applied to assess the level of miR-122-5p and IGFBP4. Western blot, transwell assays, wound-healing assays, real-time cellular invasion monitoring, in vivo study were applied to explore the function of miR-122-5p and IGFBP4. Dual luciferase reporter assays and chromatin isolation by RNA purification (ChiRP) were applied to explore the regulation of IGFBP4 by miR-122-5p.
RESULTS: Using The Cancer Genome Atlas (TCGA) data set, Sir Run Run Shaw hospital data set and bioinformatics analyses, we identified miR-122-5p as a potential tumor suppressor in ICC and validated its suppressive effect in metastasis and invasion of ICC. Transcriptome sequencing, rescue and complement experiments were used to identify insulin-like growth factor binding protein 4 (IGFBP4) as a target of miR-122-5p. The mechanism by which miR-122-5p regulates IGFBP4 was clarified by chromatin separation RNA purification technology, and dual-luciferase reporter assays. We discovered a rare novel mechanism by which miR-122-5p promotes IGFBP4 mRNA transcription by binding to its promoter region. Furthermore, in mouse orthotopic metastasis model, miR-122-5p inhibited the invasion of ICC.
CONCLUSION: In summary, our study revealed a novel mechanism of miR-122-5p and function of the miR-122-5p/IGFBP4 axis in the metastasis of ICC. We also highlighted the clinical value of miR-122-5p and IGFBP4 in inhibiting ICC invasion and metastasis.
Minimally-invasive liver resections (MILR) are increasingly conducted world-wide today. Several international consensus meetings were convened to enable the safe dissemination of laparoscopic and robotic liver resections. The Iwate difficulty scoring system (Appendix 1) was formulated in Japan to grade the difficulty of liver resections. This was to allow beginners to adopt a stepwise approach to safely perform MILR according to their experience and competency level. Although this system has been recently validated in a recent Japanese multicenter study, it has not been externally validated in a large cohort of patients. Thus far, it has only been validated in several small single center studies. Furthermore, its utility for robotic liver resections has not been well-studied.
PURPOSE: Major emergency abdominal surgery is associated with severe in-hospital complications and loss of performance. After discharge, a substantial fraction of patients are readmitted emergently; however, limited knowledge exists of the long-term consequences. The aim of this study was to examine the risks and causes of short-term (30-day) and long-term (180-day) readmission among patients undergoing major emergency abdominal surgery.
METHODS: This study included 504 patients who underwent major emergency abdominal surgery at the Zealand University Hospital between March 1, 2017, and February 28, 2019. The population was followed from 0 to 180 days after discharge, and detailed readmission information was registered. A Cox proportional hazards model was used to examine the independent risk factors for readmission within 30 and 180 days.
RESULTS: From 0 to 30 days after discharge, 161 (31.9%) patients were readmitted emergently, accumulating to 241 (47.8%) patients within 180 days after discharge. The main reasons for short-term readmission were related to the gastrointestinal tract and surgical wounds, whereas long-term readmissions were due to infections, cardiovascular complications, and abdominal pain. Stomal placement was an independent risk factor for short-term readmission, whereas an ASA score of 3 was a risk factor for both short-term and long-term readmission.
CONCLUSION: Close to 50% of all patients who underwent major emergency abdominal surgery had one or more emergency readmission within 180 days of discharge, and these data points towards the risk factors involved.
Long-term carcinogenicity studies have not been conducted with valganciclovir. However, upon oral administration, valganciclovir is rapidly and extensively converted to ganciclovir. Therefore, like ganciclovir, valganciclovir is a potential carcinogen.

Ganciclovir was carcinogenic in the mouse at oral doses that produced exposures approximately 0.1x and 1.4x, respectively, the mean drug exposure in humans following the recommended intravenous dose of 5 mg/kg, based on area under the plasma concentration curve (AUC) comparisons. At the higher dose, there was a significant increase in the incidence of tumors of the preputial gland in males, forestomach (nonglandular mucosa) in males and females, and reproductive tissues (ovaries, uterus, mammary gland, clitoral gland and vagina) and liver in females. At the lower dose, a slightly increased incidence of tumors was noted in the preputial and harderian glands in males, forestomach in males and females, and liver in females. Ganciclovir should be considered a potential carcinogen in humans.

Valganciclovir increases mutations in mouse lymphoma cells. In the mouse micronucleus assay, valganciclovir was clastogenic. Valganciclovir was not mutagenic in the Ames Salmonella assay. Ganciclovir increased mutations in mouse lymphoma cells and DNA damage in human lymphocytes in vitro. In the mouse micronucleus assay, ganciclovir was clastogenic. Ganciclovir was not mutagenic in the Ames Salmonella assay.

Valganciclovir is converted to ganciclovir and therefore is expected to have similar reproductive toxicity effects as ganciclovir [ see Warnings and Precautions (5.3)]. Ganciclovir caused decreased mating behavior, decreased fertility, and an increased incidence of embryolethality in female mice following intravenous doses that produced an exposure approximately 1.7x the mean drug exposure in humans following the dose of 5 mg per kg, based on AUC comparisons. Ganciclovir caused decreased fertility in male mice and hypospermatogenesis in mice and dogs following daily oral or intravenous administration. Systemic drug exposure (AUC) at the lowest dose showing toxicity in each species ranged from 0.03 to 0.1x the AUC of the recommended human intravenous dose. Valganciclovir caused similar effects on spermatogenesis in mice, rats, and dogs. These effects were reversible at lower doses but irreversible at higher doses. It is considered likely that ganciclovir (and valganciclovir) could cause temporary or permanent inhibition of human spermatogenesis.
NEW MATERIAL:A tris[N-substituted-2-aminoethyl]amine-iron complex expressed by formula I [R is expressed by formula II (R<1> is lower alkyl or lower alkoxycarbonyl), expressed by formula III, expressed by formula IV or expressed by formula V]. USE:Used as medical drug useful for remedy of various symptoms owing to active oxygen species, e.g. inflammatory disease (chronic rheumatism or collagen disease, etc.), chronic dermatosis, arterial sclerosis, medicinal poisoning or radiation damage, etc., having active oxygen-eliminating action with excellent stability in administration into live body without suffering to activity inhibition by serum albumin. PREPARATION:Chelate bonding is formed with N in 1 mol tetramine compound and 1mol iron to afford the aimed compound expressed by formula I. For instance, 3-methylpyridine-2-aldehyde is obtained from reaction product of 2,3- lutidine and iodine, then dissolved in methanol, thus refluxed with heating under argon gas current and reduced to obtain the teramine compound.
With a rise in antibiotic resistance and chronic infection, the metabolic response of Salmonella enterica serovar Typhimurium to various dietary conditions over time remains an understudied avenue for novel, targeted therapeutics. Elucidating how enteric pathogens respond to dietary variation not only helps us decipher the metabolic strategies leveraged for expansion but also assists in proposing targets for therapeutic interventions. In this study, we use a multi-omics approach to identify the metabolic response of Salmonella enterica serovar Typhimurium in mice on both a fibrous diet and high-fat diet over time. When comparing Salmonella gene expression between diets, we found a preferential use of respiratory electron acceptors consistent with increased inflammation in high-fat diet mice. Looking at the high-fat diet over the course of infection, we noticed heterogeneity in samples based on Salmonella ribosomal activity, which is separated into three infection phases: early, peak, and late. We identified key respiratory, carbon, and pathogenesis gene expressions descriptive of each phase. Surprisingly, we identified genes associated with host cell entry expressed throughout infection, suggesting subpopulations of Salmonella or stress-induced dysregulation. Collectively, these results highlight not only the sensitivity of Salmonella to its environment but also identify phase-specific genes that may be used as therapeutic targets to reduce infection.IMPORTANCEIdentifying novel therapeutic strategies for Salmonella infection that occur in relevant diets and over time is needed with the rise of antibiotic resistance and global shifts toward Western diets that are high in fat and low in fiber. Mice on a high-fat diet are more inflamed compared to those on a fibrous diet, creating an environment that results in more favorable energy generation for Salmonella. We observed differential gene expression across infection phases in mice over time on a high-fat diet. Together, these findings reveal the metabolic tuning of Salmonella to dietary and temporal perturbations. Research like this, which explores the dimensions of pathogen metabolic plasticity, can pave the way for rationally designed strategies to control disease.
BACKGROUND: Chronic inflammation is a factor in the pathogenesis of sarcopenia, which is characterized by low muscle mass and reduced strength. Complement C3 is important in the management of the immune network system. This study seeks to determine the relationship between serum C3 levels and body composition and sarcopenia-related status in community-dwelling older adults.
METHODS: Study participants were 269 older adults living in rural Japan. A bioelectrical impedance analysis device was used to measure body composition parameters including body mass index (BMI), body fat percentage, waist-hip-ratio, and appendicular skeletal muscle mass index (SMI). Muscle function was measured by handgrip strength and 6-m walking speed. The correlation coefficients for C3 level and measurements were calculated using Pearson correlation analysis. Participants were categorized into normal, pre-sarcopenia, dynapenia, or sarcopenia groups. Sarcopenia was defined according to 2019 Asian Working Group for Sarcopenia definition, dynapenia was defined as low muscle function without low muscle mass, and pre-sarcopenia was defined as the presence of low muscle mass only. The C3 threshold score for sarcopenia status was evaluated by receiver operating characteristic curve (ROC) analysis.
RESULTS: Significant positive correlations were found between C3 and BMI, body fat percentage, and waist-hip ratio in both sexes, and further positive correlations with SMI were found in women. The relationship with body fat percentage was particularly strong. Body composition measurements (BMI, body fat percentage, and waist- hip ratio) and C3 levels were lowest in the sarcopenia group compared with the others. ROC analysis showed that the significant threshold of C3 for discriminating between the normal and sarcopenia groups was 105 mg/dL. Multiple logistic regression analysis showed that participants with C3 < 105 mg/dL had an odds ratio of 3.27 (95% confidence interval, 1.49-7.18) for sarcopenia adjusted by sex, age and body fat percentage.
CONCLUSION: C3 levels are suggested to be related to body composition and pathophysiological functions of sarcopenia. C3 is expected to become a useful biomarker for sarcopenia, for predicting the onset of the disease and for predicting the effectiveness of interventions.
Since its invention in the late 1980s, the air-liquid-interface (ALI) culture system has been the standard in vitro model for studying human airway biology and pulmonary diseases. However, in a conventional ALI system, cells are cultured on a porous plastic membrane that is much stiffer than human airway tissues. Here, we develop a gel-ALI culture system by simply coating the plastic membrane with a thin layer of hydrogel with tunable stiffness matching that of healthy and fibrotic airway tissues. We determine the optimum gel thickness that does not impair the transport of nutrients and biomolecules essential to cell growth. We show that the gel-ALI system allows human bronchial epithelial cells (HBECs) to proliferate and differentiate into pseudostratified epithelium. Furthermore, we discover that HBECs migrate significantly faster on hydrogel substrates with stiffness matching that of fibrotic lung tissues, highlighting the importance of mechanical cues in human airway remodeling. The developed gel-ALI system provides a facile approach to studying the effects of mechanical cues in human airway biology and in modeling pulmonary diseases.NEW & NOTEWORTHY In a conventional ALI system, cells are cultured on a plastic membrane that is much stiffer than human airway tissues. We develop a gel-ALI system by coating the plastic membrane with a thin layer of hydrogel with tunable stiffness matching that of healthy and fibrotic airway tissues. We discover that human bronchial epithelial cells migrate significantly faster on hydrogel substrates with pathological stiffness, highlighting the importance of mechanical cues in human airway remodeling.
Background and Objectives: PIN1 is overexpressed in several human cancers, including prostate cancer, breast cancer, and oral squamous carcinomas. Juglone (J), derived from walnut, was reported to selectively inhibit PIN1 by modifying its sulfhydryl groups. In this study, the potential effects of juglone, also known as PIN1 inhibitor, on oral cancer and carcinogenesis were investigated at the molecular level. Materials and Methods: 4-Nitroquinoline N-oxide (4-NQO) was used to create an oral cancer model in animals. Wistar rats were divided into five groups: Control, NQO, Juglone, NQO+J, and NQO+J*. The control group received the basal diet and tap water throughout the experiment. The NQO group received 4-NQO for 8 weeks in drinking water only. The Juglone group was administered intraperitoneally in a juglone solution for 10 weeks (1 mg/kg/day). The NQO+J group received 4-NQO in drinking water for 8 weeks, starting 1 week after the cessation of 4-NQO treatment. They were then administered intraperitoneally in a juglone solution for 10 weeks. (1 mg/kg/day). NQO+J* group: received 4 NQO for 8 weeks in drinking water and administered intraperitoneally in a juglone solution for 10 weeks (1 mg/kg/day). They were sacrificed at the end of the 22-week experimental period. The tongue tissues of the rats were isolated after the experiment, morphological changes were investigated by histological examinations, and the molecular apoptotic process was investigated by rt-qPCR and western blot. Results: Histological results indicate that tumors are formed in the tongue tissue with 4-NQO, and juglone treatment largely corrects the epithelial changes that developed with 4-NQO. It has been determined that apoptotic factors p53, Bax, and caspases are induced by the effect of juglone, while antiapoptotic factors such as Bcl-2 are suppressed. However, it was observed that the positive effects were more pronounced in rats given juglone together with 4-NQO. Conclusions: The use of PIN1 inhibitors such as juglone in place of existing therapeutic approaches might be a promising and novel approach to the preservation and treatment of oral cancer and carcinogenesis. However, further research is required to investigate the practical application of such inhibitors.
The present invention provides methods of treatment of patients suffering from the complications of blood sugar disorders: diabetic peripheral neuropathy and diabetic nephropathy by administration of IGF-1 via protein therapy or gene therapy. It relates to methods of treating an individual having a diabetic disorder or a hyperglycemic disorder, comprising administering to the individual an effective amount of a DNA vector expressing IGF-1Eb or IGF-1Ec in vivo or an effective amount of at the IGF-1Eb or IGF-1Ec protein in the early hyperalgesia stage or in patients that have advanced to the hyposensitivity stage. Treatment at the early hyperalgesia stage prevents subsequent hyposensitivity with increases or maintenance of sensory nerve function. IGF-1Eb or IGF-1Ec treatment also increases muscle mass and improves overall mobility, which indicates a treatment-related improvement in motor function. Treatment with IGF-1Eb or IGF-1Ec at the hyposensitivity stage reverses hyposensitivity and improves muscle mass and overall health. Systemic IGF-1 provides a therapeutic modality for treating hyposensitivity associated with DPN. In addition, IGF-1Eb or IGF-1Ec provides a therapeutic modality for treating diabetic nephropathy. IGF-1Eb or IGF-1Ec improves renal function as evidenced by a modulation in serum albumin concentration and a reduction in urine volume and protein levels. IGF-1Eb or IGF-1Ec also reduces diabetic glomerulosclerosis.
BACKGROUND: This study aimed to estimate the prevalence of obesity, overweight, and underweight in celiac disease (CD) at diagnosis before starting the Gluten-free diet (GFD).
METHODS: A comprehensive search was conducted in PubMed, Embase, Scopus, and Web of Science until July 2024 to find the cross-sectional and longitudinal studies that measured the body mass index (BMI) in CD patients at diagnosis. The risk of bias assessment was conducted using the Newcastle-Ottawa Quality Assessment scale. Meta-regression analyses were applied to understand whether weight status is associated with CD.
RESULTS: A total of 23 studies involving 15,299 CD patients and 815,167 healthy individuals were included in this study. In newly diagnosed CD patients, pooled estimates of the prevalence of obesity, overweight, and underweight before GFD were 11.78%, 18.42%, and 11.04%, respectively. The prevalence of overweight and obesity in newly diagnosed CD patients increased from 22.15% in 2003-2009 to 32.51% in 2016-2021. Meta-regression analyses indicated that the CD patients with higher BMI had a higher mean age (p = 0.001), and female gender had a marginally significant (p = 0.055) association with higher BMI. Only a few CD patients were underweight at the time of diagnosis, and more patients were overweight/obese.
CONCLUSIONS: our meta-analysis demonstrated that only a few CD patients were underweight at the time of diagnosis, and almost 37% were overweight or obese. Meta-regression showed a significant association between higher BMI and higher mean age and female gender. A delay or failure for diagnosis of CD is more common in overweight/obese patients, resulting in more progression of the disease and counteracting any advantages of diagnosis.
The present invention discloses an improved process for the extraction of alpha yohimbine from leaves of  Rauwolfia  species, preferably  Rauwolfia canescens/Rauwolfia tetraphylla . Process involves use of non-polar alcoholic solvent e.g. methanol for precipitating the compound of interest, repetitive washing with halogenated solvents and washing with hexane or petroleum ether to obtain high yields of high purity extract. Use of organic acids such as tartaric acid, acetic acid and organic solvent ethyl acetate etc. is eliminated making the process less time consuming and economical. The yield of the final product is 50-60%   higher i.e. 600-670 mg/100g dry leaves, than prior art process. Further, the extract obtained by the process of present invention contains yohimbine hydrochloride as a marker compound in analytically detectable amounts of more than 0.1% of the extract.
FIELD: medicine. ^ SUBSTANCE: invention relates to veterinary science. The technique involves blood serum examination in an immunodiffusion reaction. As a diagnosticum, an antigen prepared by mechanical mixing of equal proportions of the O-polysaccharide M-antigen produced of the vaccine strain B melitensis Rev-1, and the O-polysaccharide A-antigen produced of the vaccine strain B abortus 19 is used. ^ EFFECT: use of the offered technique provides higher diagnostic accuracy and reliability of bovine and sheep brucellosis. ^ 3 tbl, 3 ex
Patients receive pembrolizumab IV over 30 minutes on day 1 and enobosarm PO QD on days 1-21. Courses repeat every 21 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity.
Participants receive sorafenib on days 1-28, and nivolumab IV over 30 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.