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

Based on findings in animals, allopurinol may cause fetal harm when administered to a pregnant woman. Adverse developmental outcomes have been described in exposed animals (see Data). Allopurinol and its metabolite oxypurinol have been shown to cross the placenta following administration of maternal allopurinol. 

Available limited published data on allopurinol use in pregnant women do not demonstrate a clear pattern or increase in frequency of adverse developmental outcomes. Among approximately 50 pregnancies described in published literature, 2 infants with major congenital malformations have been reported with following maternal allopurinol exposure. Advise pregnant women of the potential risk to a fetus. 

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. 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. 

Data

Animal Data

There was no evidence of fetotoxicity or teratogenicity in rats or rabbits treated during the period of organogenesis with oral allopurinol at doses up to 200 mg/kg/day and up to 100 mg/kg/day, respectively (about three times the human dose on a mg/m2 basis). However, there is a published report in pregnant mice that single intraperitoneal doses of 50 or 100 mg/kg (about 1/3 or 3/4 the human dose on a mg/m2 basis) of allopurinol on gestation days 10 or 13 produced significant increases in fetal deaths and teratogenic effects (cleft palate, harelip, and digital defects). It is uncertain whether these findings represented a fetal effect or an effect secondary to maternal toxicity. In another published study with no reported maternal toxicity, allopurinol administered orally at 15 or 45 mg/kg to pregnant rats during organogenesis caused embryonic resorptions, growth retardation, decreased fetal weight, and skeletal, liver, kidney, and brain abnormalities. In rats, maternal treatment with allopurinol in normoxic pregnancy has been shown to increase the cardiac protein levels of sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2a) in the adult male offspring. The mechanism underlying this effect is not understood. However, this effect was not matched by an increase in left ventricular end diastolic pressure or sympathetic dominance in hearts of adult male offspring of normoxic pregnancy treated with allopurinol.
INTRODUCTION: Long term effects after hysterectomy, such as a worsening of pelvic floor and sexual function, have been studied with diverse results. Therefore, we investigated the long-term effects of hysterectomy for benign indication on pelvic floor and sexual function as well as differences in outcome depending on mode of hysterectomy.
MATERIAL AND METHODS: In a prospective clinical cohort study, we included 260 women scheduled for hysterectomy who answered validated questionnaires; pelvic floor impact questionnaire (PFIQ-7), pelvic floor distress inventory (PFDI-20) and female sexual function index (FSFI). Participants were followed up to 3 years after surgery. Nonparametric statistics and mixed effect models were used in analyses of the data.
RESULTS: After exclusions, 242 women remained in the study, with a response rate at the 3-year follow-up of 154/242 (63.6%) for all questionnaires. There was an improvement of pelvic floor function with a mean score of PFIQ-7 at baseline of 42.5 (SD 51.7) and at 3 years 22.7 (SD 49.4), (p < 0.001) and mean score of PFDI-20 at baseline was 69.6 (SD 51.1) and at 3 years 56.2 (SD 54.6), (p = 0.001). A deterioration of sexual function was seen among the sexually active women after 3 years with a mean score of FSFI at baseline 25.2 (SD 6.6) and after 3 years 21.6 (SD 10.1), (p < 0.001). However, this was not consistent with the unaltered sexual function for the whole cohort. No difference in pelvic floor or sexual function was detected when comparing robotic assisted laparoscopic hysterectomy, laparoscopic hysterectomy and abdominal hysterectomy.
CONCLUSIONS: Three years after surgery robotic assisted laparoscopic hysterectomy, total laparoscopic hysterectomy and abdominal hysterectomy improve pelvic floor function to the same extent. Among the sexually active women, a decline of sexual function was seen after 3 years, not consistent with the entire cohort and independent of surgical methods. Whether this is a trend associated with aging or menopausal transition remains to be studied.
Practitioners should give the following information and instructions to patients receiving barbiturates. 

  1. The use of barbiturates carries with it an associated risk of psychological and/or physical dependence. The patient should be warned against increasing the dose of the drug without consulting a physician. 
  2. Barbiturates may impair mental and/or physical abilities required for the performance of potentially hazardous tasks (e.g., driving, operating machinery, etc.). 
  3. Alcohol should not be consumed while taking barbiturates. Concurrent use of the barbiturates with other CNS depressants (e.g., alcohol, narcotics, tranquilizers, and antihistamines) may result in additional CNS depressant effects. 
  4. Effect of anesthetic and sedation drugs on early brain development  
Studies conducted in young animals and children suggest repeated or prolonged use of general anesthetic or sedation drugs in children younger than 3 years may have negative effects on their developing brains. Discuss with parents and caregivers the benefits, risks, and timing and duration of surgery or procedures requiring anesthetic and sedation drugs. Because some animal data suggest that the window of vulnerability includes the 3rd trimester of pregnancy, discuss with pregnant women the benefits, risks, and timing and duration of surgery or procedures requiring anesthetic and sedation drugs. (See “Warnings-Pediatric Neurotoxicity”.)
Sarcomas are heterogeneous connective tissue malignancies that have been historically categorized into soft tissue and bone cancers. Although multimodal therapies are implemented, many sarcoma subtypes are still difficult to treat. Lipids play vital roles in cellular activities; however, ectopic levels of lipid metabolites have an impact on tumor recurrence, metastasis, and drug resistance. Thus, precision therapies targeting lipid metabolism in sarcoma need to be explored. In this study, we performed a comprehensive analysis of molecular stratification based on lipid metabolism-associated genes (LMAGs) using both public datasets and the data of patients in our cohort and constructed a novel prognostic model consisting of squalene epoxidase (SQLE) and tumor necrosis factor (TNF). We first integrated information on gene expression profile and survival outcomes to divide TCGA sarcoma patients into high- and low-risk subgroups and further revealed the prognosis value of the metabolic signature and immune infiltration of patients in both groups, thus proposing various therapeutic recommendations for sarcoma. We observed that the low-risk sarcoma patients in the TCGA-SARC cohort were characterized by high proportions of immune cells and increased expression of immune checkpoint genes. Subsequently, this lipid metabolic signature was validated in four external independent sarcoma datasets including the CHCAMS cohort. Notably, SQLE, a rate-limiting enzyme in cholesterol biosynthesis, was identified as a potential therapeutic target for sarcoma. Knockdown of SQLE substantially inhibited cell proliferation and colony formation while promoting the apoptosis of sarcoma cells. Terbinafine, an inhibitor of SQLE, displayed similar tumor suppression capacity in vitro. The prognostic predictive model and the potential drug target SQLE might serve as valuable hints for further in-depth biological, diagnostic, and therapeutic exploration of sarcoma.
Tertiary lymphoid structures are immune cell aggregates linked with cancer outcomes, but their interactions with tumour cell aggregates are unclear. Using nasopharyngeal carcinoma as a model, here we analyse single-cell transcriptomes of 343,829 cells from 77 biopsy and blood samples and spatially-resolved transcriptomes of 31,316 spots from 15 tumours to decipher their components and interactions with tumour cell aggregates. We identify essential cell populations in tertiary lymphoid structure, including CXCL13+ cancer-associated fibroblasts, stem-like CXCL13+CD8+ T cells, and B and T follicular helper cells. Our study shows that germinal centre reaction matures plasma cells. These plasma cells intersperse with tumour cell aggregates, promoting apoptosis of EBV-related malignant cells and enhancing immunotherapy response. CXCL13+ cancer-associated fibroblasts promote B cell adhesion and antibody production, activating CXCL13+CD8+ T cells that become exhausted in tumour cell aggregates. Tertiary lymphoid structure-related cell signatures correlate with prognosis and PD-1 blockade response, offering insights for therapeutic strategies in cancers.
Severe acquired aplastic anemia (SAA) has a poor prognosis if untreated. Bone marrow transplantation is available to only a minority of patients due to lack of a matched sibling donor, advanced age of the patient, or cost. Clinical studies at NIH and elsewhere have demonstrated excellent response rates and improved survival with immunosuppressive treatments. Laboratory data implicate underlying cytotoxic T-lymphocyte-mediated suppression of hematopoiesis as the likely proximal cause of disease in most patients. In earlier clinical protocols we treated SAA with cyclosporine A (CSA) (86-H-0007), antithymocyte globulin (ATG) (87-H-0124), and combined ATG and CSA (90-H-0146). While intensive immunosuppression is most effective, relapse is common and some patients also develop second hematologic complications like myelodysplasia. In this protocol, we modify our regimen by delaying the introduction of cyclosporine to promote ATG tolerizing effects and adding mycophenolate mofetil (MMF), a new agent that, like ATG may be relatively specific for activated lymphocytes, in an effort to reduce the high relapse rate.
Severe adversity and trauma in early childhood have been associated with a highly increased risk for a variety of psychiatric disorders, lasting into adulthood. This increased risk is accompanied by a set of biological changes ranging from changes in cortical thickness to endocrinological changes. At a behavioral level, children with complex PTSD (developmental trauma disorder) show severe and long-lasting negative effects. Such children exhibit a wide range of symptoms: affect dysregulation, attention difficulties, impairment in interpersonal relationships, aggressive and dissociative behaviour, disturbances of cognition. Corresponding alterations in neural networking and brain development are well studied. Although evidence-based treatment approaches for children with non-complex PTSD exist, complex-traumatized children have no well-evaluated treatments. Furthermore, early intervention can prevent the chronification and exacerbation of symptoms and promote social adaptation and participation.The following topics will be addressed: (1) brain development (Multimodal MRI (mMRI) including anatomical (T1-MPRAGE, T2-FLAIR, DTI-Diffusion Tensor Imaging) and functional MRI measurements (resting-state functional MRI, task fMRI (presenting affective pictures according to the International Affective Picture System, IAPS), EEG); (2) alterations in neuroendocrinological systems involved in stress regulation (Cortisol, Oxytocin, Vasopressin); (3) behavioral symptoms; (4) cognitive functioning; (5) attachment representations of children and their primary caregivers;
The impacts from diabetes are both patient related and healthcare based. DFU is associated with a high mortality rate at 34% at 1 year. There is an associated higher limb amputation rate from DFU than other causes. The high mortality rate, high amputation rate and increased socio-economic burden means providing high quality evidence based DFU service provision should be a NHS priority. Offloading is recognised as the priority treatment for healing neuropathic and neuro-ischaemic plantar foot ulcers. Since the provision of non removable devices or total contact casts (TCC) is poor, options have to be available that are equivalent in effectiveness at off loading and healing DFU. By improving the quality of offloading choices and acceptability for devices this will improve healing rates and reduce the cost burden where currently in the UK diabetic foot care in 2015 accounted for 0.6%/585.5million pounds of the NHS budget. The evidence for effectiveness of non removable devices is poor. Therefore any device that offloads to the equivalent or more than previous devices and current usual standard of care must be evidenced. The new PulseFlow DF boot is such a device which claims to off load but has little or no evidence on DFU subjects. Thus the primary aim of this study is to observe forefoot plantar pressures in a cross sectional purposively selected sample compared to usual standard of care.
Gastric cancer patients with peritoneal metastasis undergo pulsed low dose rate 3-dimensional conformal radiation therapy, QD, 5 days a week for 25 days. Treatment continues in the absence of disease progression or unacceptable toxicity.
This multi-site randomized, controlled trial will measure the effectiveness of the diaphragm in preventing heterosexual acquisition of HIV infection among women. This Phase III study is powered to detect effectiveness (biological efficacy combined with adherence) of 33 percent. Women in South Africa and Zimbabwe (N=4,500) at risk of contracting HIV will be invited to participate and will be followed for up to 24 months, with a total study duration of 4 years. All women will receive safer-sex counseling, free male condoms and diagnosis and treatment of sexually transmitted infections (STIs). Half of the participants will be randomly selected to receive an Ortho All-Flex latex diaphragm and Replens lubricant gel. We will assess whether women using diaphragms and lubricant gel have lower rates of HIV or STI infection than do their non-diaphragm and gel counterparts. Additionally, we will investigate the long-term acceptability of the diaphragm in this study population.
The cost of healthcare in the United States has risen precipitously over the last forty years. In 2014, healthcare spending surpassed $3 trillion and accounted for 17.5 percent of the national gross domestic product. The Institute of Medicine's report "Best Care at Lower Cost" estimated that 30 percent, or approximately $900 billion in 2014, of healthcare expenditures are wasted. Given this wasted spending, great urgency has been placed on curbing the ever-increasing cost of healthcare while simultaneously improving quality and patient safety. Despite improvements in mortality associated with cardiovascular disease over the last two decades, the cost of cardiovascular care continues to rise and is estimated to be in excess of $186 billion by 2023. A number of studies have been performed evaluating the cost-effectiveness and appropriate use of routine transthoracic echocardiography; nonetheless, there is little evidence that the results of these studies have been translated into clinical practice. In order to close the gap between the literature and clinical practice, we plan to initiate a combined didactic and data feedback program that will present the current literature and in-hospital charges associated with echocardiography to practicing clinicians on inpatient cardiology services. We will measure the effect of our intervention on average per-patient in-hospital charges as well as usage rates and other clinical outcomes.

Research Design and Methods: The investigators will perform a prospective, controlled cohort study period comparing the effect of a combined didactic and data feedback intervention on in-hospital charges, usage rates, and clinical outcomes to providers. The investigator's intervention will consist of a biweekly email to three house staff-run cardiology services at VUMC presenting the in-hospital charges and appropriate use of echocardiography per ACC/AHA guidlines. A weekly email will also be sent to the intervention services detailing their team's in-hospital charges for echocardiograms during the preceding week. Usage and in-hospital charges will be measured using a custom tableau which captures all orders placed in the HeoWiz ordering program and the raw master charges. The investigators will utilize a pre and post intervention design to study primary and secondary outcomes. The primary outcome will be average echocardiography charges per team. The secondary outcomes will be echocardiograms performed per team per month, and number of focused echocardiograms performed per team per month. Quality of care will be assessed by monitoring 30 day readmission rate, and index hospitalization mortality.
Spinal cord is composed of specialized neural networks, capable of executing different functions. Although the command for lower-limb functions such as standing and walking is primarily delivered from the brain, it was found that the spinal cord circuits not only execute it but also maintain the task and control the dynamics with proper feedback mechanisms with it's reflex circuitry. Simple bipedal standing and walking requires spatiotemporal coordination of muscles, limb joints, balance etc., their adaptation and control in gravity. For human, these physiological activities are well choreographed by sets of neural networks. In combination with afferent proprioceptive inputs, these network circuits work with the motor periphery to generate a series of motor acts during each task. Normally, the activity of these spinal networks are regulated supraspinally and by peripheral sensory inputs. In case of the loss of supraspinal inputs, resultant of a Stroke or spinal cord injury (SCI), motor tasks maybe enabled by directly activating these specialized spinal cord networks via external stimuli. Recent studies have demonstrated that neuromodulation via spinal cord stimulation can effectively restore lower-extremity functions in patients with chronic neurological injuries.

Traumatic injury to the central nervous system (CNS) such as SCI is devastating events leaving patients with impairment of motor, sensory and autonomic functions. Mainstay for the treatment is still limited to rehabilitation by physical therapy and training. In few patients, however, neuroplasticity and repair mechanisms are considered to contribute to recovery of paresis in the acute stage of the injury and stops in the chronic stage. But, recent groundbreaking studies have shown that the recovery can be further amplified in the chronic stage by the novel treatment of trans-spinal electrical stimulation. However, the rehabilitation related to this recovery is not very significant, and thus it is a challenge to be convinced with the efficacy of this new therapy. A combination therapy of trans-spinal electrical stimulation along with body-weight would promote better recovery and benefit the patients more. The current study will further assist the researchers to design such combinational therapeutic intervention for neurologically impaired patients to stimulate to walk again. Successful translation of this novel technology would facilitate the paraplegic community to become more healthy, independent and happy.
PURPOSE: The aim of our study is to examine the morphometry of the P1 segment of the posterior cerebral artery (P1) and the posterior communicating artery (PcomA) and to present a descriptive classification according to morphometric findings.
METHODS: 340 hemispheres from 170 cadavers were included. The outer diameters of P1 and PcomA were measured with ImageJ software. Then, the configurations of the posterior cerebral artery were revealed as fetal, adult and transitional. The findings were correlated with the demographic information of the cadavers such as gender, body mass index (BMI), age.
RESULTS: According to the morphometric findings, 83.75%, 13.85% and 2.40% of the posterior cerebral arteries were found to be adult, fetal and transitional, respectively. The fetal type was more common in cadavers aged 60 years and older (13.73%) compared to the 18-39 and 40-59 age groups. In addition, P1 and PcomA diameters also increased with age. Fetal and transtional types showed a similar low distribution in people with low (< 18.5), normal (18.5-24.9), overweight (25-29.9) and obese (> 30) BMI, whereas adult type was found in cadavers with a normal BMI of 140/303.
CONCLUSION: We believe that the findings of our study will contribute to the planning of neurointerventional procedures, the development of endovascular devices, the success of invasive procedures and the reduction of complications.
Tolcapone did not influence the effect of ephedrine, an indirect sympathomimetic, on hemodynamic parameters or plasma catecholamine levels, either at rest or during exercise. Since tolcapone did not alter the tolerability of ephedrine, these drugs can be co-administered.

When Tolcapone tablets was given together with levodopa/carbidopa and desipramine, there was no significant change in blood pressure, pulse rate and plasma concentrations of desipramine. Overall, the frequency of adverse events increased slightly. These adverse events were predictable based on the known adverse reactions to each of the three drugs individually. Therefore, caution should be exercised when desipramine is administered to Parkinson's disease patients being treated with Tolcapone tablets and levodopa/carbidopa.

In clinical trials, patients receiving Tolcapone tablets/levodopa preparations reported a similar adverse event profile independent of whether or not they were also concomitantly administered selegiline (a selective MAO-B inhibitor).
A one hour infusion of a single 8mg/kg dose (max. 800mg) of tocilizumab to attenuate systemic inflammation after out-of-hospital cardiac arrest, given as early as possible after hospital admission.
A method of forming an array of viable cells is carried out by ink-jet printing a cellular composition containing said cells on a substrate. At least two different types of viable mammalian cells are printed on the substrate, the at least two different types of viable mammalian cells selected to together form a tissue. In some embodiments at least three or four different viable mammalian cells are printed on the substrate, the cells selected to together form a tissue. In some embodiments one of the viable mammalian cell types is a stem cell. In some embodiments the method further comprises printing at least one support compound on the substrate, the support compound selected to form a tissue together with said cells. In some embodiments the method further comprises printing at least one growth factor on the substrate, the growth factor selected to cause the cells to form a tissue.
GLI1, a key transcription factor of the Hedgehog (Hh) signaling pathway, plays an important role in the development of cancer. However, the function and mechanisms by which GLI1 regulates gene transcription are not fully understood in gastric cancer (GC). Here, we found that GLI1 induced the proliferation and metastasis of GC cells, accompanied by transcriptional upregulation of INHBA. This increased INHBA expression exerted a promoting activity on Smads signaling and then transcriptionally activated GLI1 expression. Notably, our results demonstrate that disrupting the interaction between GLI1 and INHBA could inhibit GC tumorigenesis in vivo. More intriguingly, we confirmed the N6-methyladenosine (m6A) activation mechanism of the Helicobacter pylori/FTO/YTHDF2/GLI1 pathway in GC cells. In conclusion, our study confirmed that the GLI1/INHBA positive feedback loop influences GC progression and revealed the mechanism by which H. pylori upregulates GLI1 expression through m6A modification. This positive GLI1/INHBA feedback loop suggests a novel noncanonical mechanism of GLI1 activity in GC and provides potential therapeutic targets for GC treatment.