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

The limited available data with BAXDELA use in pregnant women are insufficient to inform a drug-associated risk of major birth defects and miscarriages. When delafloxacin (as the N-methyl glucamine salt) was administered orally to rats during the period of organogenesis, no malformations or fetal death were observed at up to 7 times the estimated clinical exposure based on AUC. When rats were dosed intravenously in late pregnancy and through lactation, there were no adverse effects on offspring at exposures approximating the clinical intravenous (IV) exposure based on AUC [see Data].

The 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 2–4% and 15–20%, respectively.

Data

Animal Data

In embryo-fetal studies, oral administration of delafloxacin to pregnant rats during the period of major organogenesis resulted in maternal toxicity and reduced fetal body weights at the highest dose (1600 mg/kg/day) and fetal ossification delays at all doses. No malformations were reported up to the highest dose tested (approximately 7 times the estimated human plasma exposure based on AUC). The lowest dose, 200 mg/kg/day (approximately 2.5 times the estimated human plasma exposure based on AUC), was still toxic to the fetus, based on ossification delays. In rabbits, a species known to be extremely sensitive to maternal toxicity of antibacterial drugs, no embryo-fetal developmental toxicity was observed up to the highest dose which induced maternal toxicity (1.6 mg/kg/day, or approximately 0.01 times the estimated human plasma exposure based on AUC). In a pre-postnatal study in rats of IV administered delafloxacin, dams at the highest dose tested (120 mg/kg/day) exhibited slightly lower body weights and slightly longer gestation length than control animals. Exposure at that dose was estimated to be approximately 5 times human plasma exposure based on AUC, as determined in a separate shorter term study at an earlier stage of pregnancy. Effects on pups at that dose included increased mortality during lactation, small stature, and lower body weights, but no changes in learning and memory, sensory function, locomotor activity, developmental landmarks, or reproductive performance were reported. The No Adverse Effect Level (NOAEL) for maternal toxicity pup development in that study was 60 mg/kg/day (approximately 580 mg/day IV for a 60 kg patient, or just below the clinical IV dose).
PURPOSE:A rubber based adhesive plaster, obtained by incorporating an extract of a rosemary with an organic solvent with an extract of the rosemary with a hydrous organic solvent, and capable of keeping a chemical stable without decomposition thereof. CONSTITUTION:A rubber based adhesive plaster obtained by incorporating (A) 0.01-6wt% extract of a rosemary with an organic solvent with (B) 0.01-6wt% extract of the rosemary with a hydrous organic solvent at (1/10)-10 mixing ratio between the two components. A volatile polar solvent, e.g. a lower alcohol or lower ketone, compatible with water in any proportion or a weakly polar solvent, e.g. xylene, tetrahydrofuran (THF) or n-hexane, is cited as the solvent for the extract (A). Ethanol is preferred for the solvent for the extract (B). If the rubber based adhesive material is hydrophobic, the extract (A) is used in a larger amount. If the rubber based adhesive is hydrophilic, the amount of the extract (B) is preferably increased. In production of the plaster, these components are preferably added thereto in as early a period as possible.
BACKGROUND: Total ankle replacements (TARs) have rapidly advanced in terms of volume, technique, design, and indications. However, TARs are still at risk for early mechanical failure and revision. Prior studies have investigated potential risk factors for failure, but have been limited to smaller series or older implants. This study sought to identify risk factors for early mechanical failure in modern TAR.
METHODS: This is a retrospective study of a single-institution registry. Five surgeons contributed cases involving patients who underwent a primary TAR with any implant. Implants were grouped on the basis of the type of fixation. The primary outcome was early mechanical failure (revision with component removal for a non-infectious etiology, that is, subsidence, aseptic loosening, and/or malalignment). Logistic regression determined the effects of age, weight, hindfoot arthrodesis, implant type, and radiographic deformity on failure.
RESULTS: The 731 included patients had a mean follow-up of 2.7 years. Ten percent (71 patients) had hindfoot arthrodesis. There were 33 mechanical failures (4.5%) at a mean of 1.7 years after the index surgical procedure. Our model demonstrated that hindfoot arthrodesis was associated with 2.7 times greater odds of failure (p = 0.045), every 10 kg of body weight increased the odds of tibial-sided failure by 1.29 times (p = 0.039), and implants with more extensive tibial fixation (stems or keels) lowered the odds of tibial failure by 95% (p = 0.031).
CONCLUSIONS: In patients with uncontrollable risk factors (hindfoot arthrodesis) or risk factors that may or may not be modifiable by the patient (weight), implants with more robust tibial fixation may be able to reduce the risk of early mechanical failure. Further research is warranted to support efforts to decrease early failure in TAR.
LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.
While it is well known that mental fatigue impairs fine motor performance, the investigation into its neural basis remains scant. Here, we investigate the impact of mental fatigue on fine motor performance and explore its underlying neural network connectivity mechanisms. A total of 24 healthy male university students were recruited and randomly divided into two groups: a mental fatigue group (MF) and a control group (Control). Both groups completed 50 dart throws, while electroencephalography (EEG) data were collected. Following the Stroop intervention, participants in the MF group exhibited a decrease in Stroop task accuracy and throwing performance, and an increase in reaction time along with VAS and NASA scores. The EEG data during dart-throwing revealed that the network connectivity strength of theta oscillations in the frontal and left central regions was significantly higher in the MF group compared with the Control group, while the network connectivity strength of alpha oscillations in the left parietal region was significantly enhanced. The interregional connectivity within the theta and alpha rhythm bands, particularly in the frontal-central-parietal network connections, also showed a significant increase in the MF group. Mental fatigue impairs dart throwing performance and is accompanied by increased connectivity in alpha and theta.
LY900014 (100 units/milliliter (U/mL)) is a mealtime insulin administered subcutaneously (SC) 0-2 minutes prior to each meal in combination with insulin glargine (100 U/mL) SC as long-acting insulin. Mealtime (bolus) and long-acting (basal) insulin doses were titrated to achieve glucose targets during the study.
Participants can opt to receive HAC 22L after a control period of 6 months. Participants will have the opportunity to receive an optional touch-up treatment and will be followed for an additional 6 months period.
Despite ongoing eradication efforts, malaria remains a major public health challenge in Africa where annually, \~250,000 children with malaria experience a neurologic injury with subsequent neurodisability. In other central nervous system (CNS) disorders, fever is a recognized cause of worsening secondary neurologic injury and ex-tensive efforts are made to avoid hyperthermia or induce hypothermia for neuroprotection. Evidence indicates that among children with CNS malaria a higher temperature during the acute illness is a risk factor for post-infectious neurologic sequelae. As such, aggressive antipyretic therapy may be warranted, at least among children with complicated malaria who are at substantial risk of brain injury. Previous clinical trials conducted primarily in children with uncomplicated malaria and using only a single antipyretic medication have shown limited benefits in terms of fever reduction; however, no studies to date have examined malaria fever management using dual therapies. Enthusiasm for aggressive fever reduction measures among clinicians caring for children with malaria has been curbed by in vitro findings that malaria parasite replication slows at higher temperatures and a single clinical trial in which peripheral parasite clearance was slower in children receiving treatment for fever. However, the relationship between temperature and malaria parasite behavior is complex. Additional in vitro data suggest that at febrile temperatures uninfected red blood cells (RBCs) are more likely to adhere to infected RBCs, worsening the process of sequestration, increasing the parasite burden obstructing microvascular cerebral blood flow, and perhaps contributing to ongoing immunopathogenesis in CNS malaria. In this exploratory clinical trial of aggressive antipyretic therapy, children hospitalized with CNS malaria will be randomized to usual care (acetaminophen every 6 hours for a temperature ≥ 38.5ºC) vs. prophylactic acetaminophen and ibuprofen every 6 hours for 72 hours. This proof-of-concept study will determine whether aggressive antipyretic therapy results in a lower mean maximum temperature relative to usual care. Serial quantitative levels of histidine rich protein 2 (HRP2), a P. falciparum-specific protein that facilitates estimates of whole body parasite burden and CNS parasite sequestration, will also be collected to clarify the relationship between antipyretic use and in vivo parasite behavior. Findings from this study will determine whether a Phase III clinical trial of aggressive antipyretics for neuroprotection in pediatric CNS malaria should be undertaken. This study will take place in Zambia and Malawi, where prior NIH-funded collaborations have assisted in developing the substantial infrastructure needed to undertake a clinical trial of this nature.
The invention discloses a paclitaxel alhumin submicron for injection. The paclitaxel alhumin submicron comprises 1-10% (W/W) of paclitaxel, 10-80%(W/W) of alhumin and 10-85% (W/W) of freeze-drying protective agent. The invention also discloses a preparation method of the paclitaxel alhumin submicron. The method comprises the following steps of 1) adding paclitaxel into tert-butyl alcohol, stirring and dissolving to be used as an organic phase; 2) adding the alhumin and the freeze-drying protective agent to water or a buffer with a pH within 6.0-8.5, stirring and dissolving to be used as a water phase; 3) adding the organic phase into water with stirring, stirring and dissolving, filtering and degerming through a millipore filtration method, and placing in a clean container; 4) freezing at -30- -50 DEG C, removing tert-butyl alcohol and water through freeze-drying by a lyophilizer to obtain freeze-drying powder with good profile and loosening quality. During usage, the freeze-drying powder is added to a solvent for injection and redissolved, so that paclitaxel alhumin submicrons with an average particle size of 100-600nm are formed. The paclitaxel alhumin submicron for injection of the invention has advantages of a simple preparation technology, no high toxic organic solvent and long-term storage, etc.
Lung toxicity was observed in 2 different strains of rats and in dogs and monkeys. The primary findings included increase in lung weight, associated with smooth muscle hypertrophy, hyperdistention of the alveoli, and/or increased collagen. Insufficient or lack of pulmonary collapse at necropsy, generally correlated with microscopic changes, was observed in all species. In rats and monkeys, lung toxicity was observed at all oral doses tested in chronic studies. The lowest doses tested in rats (0.05 mg/kg/day in the 2-year carcinogenicity study) and monkeys (0.5 mg/kg/day in the 39-week toxicity study) are similar to and approximately 20 times the RHD on a mg/m2 basis, respectively. 

  


In the 52-week oral study in monkeys, respiratory distress associated with ketamine administration was observed at doses of 3 and 10 mg/kg/day; the most affected animal became hypoxic and required oxygenation. As ketamine is not generally associated with respiratory depression, this effect was attributed to fingolimod. In a subsequent study in rats, ketamine was shown to potentiate the bronchoconstrictive effects of fingolimod. The relevance of these findings to humans is unknown.
The prevalence of metabolic disorders including dyslipidemia increases as women transition from premenopause to postmenopause. This increases the risk for morbidity and mortality from cardiovascular diseases. Carduus marianus is a homeopathic medicine that traditionally has been used for hepatic diseases. Silymarin, isolated from Carduus marianus, owe its therapeutic and hepatoprotective effects to its strong antioxidant and anti-inflammatory properties. Carduus marianus is frequently used in clinical practice and reduces plasma level of triglycerides, total cholesterol and LDL in humans with dyslipidemia. Not all homeopaths agree on dosage and potency when prescribing homeopathic medicines. The aim of this study is to assess: (1) the most effective dose of Carduus marianus in centesimal scale for reducing hypertriglyceridemia and/or hypercholesterolemia in climacteric women; (2) the effect of Carduus marianus in other metabolic parameters (glucose, glycosylated hemoglobin, insulin resistance, weight, body mass index, waist circumference).

This is a 8-week, double-blind, randomized, parallel, four-group, dose-response study to assess the safety and efficacy of Carduus marianus in 6cH, 12cH, 30cH and placebo plus diet and exercise, for reducing hypertriglyceridemia and/or hypercholesterolemia in climacteric women.
Participants allocated to the waiting list control group may continue previously initiated standard therapy, but must not initiate any new treatment. They will be asked not to undergo acupuncture treatment for any condition within the next 3 months. After this period they are offered 10 acupuncture treatments over a period of 3 months.
Sun and ultraviolet light exposure has both short term and long term effects on skin. While the short term effects, such as sunburn, are understood, chronic long-term sun exposure can cause changes to the skin that are not well characterized. One particular alteration may be how the skin consumes oxygen, a change that may be linked to biochemical alterations that have been observed in past studies. Measuring skin oxygen consumption has traditionally been difficult as the tools available have not been easy to incorporate into clinical studies. In this study, we overcome this barrier through the use of a new non-invasive oxygen-sensing device that can rapidly measure skin oxygenation properties such as oxygen consumption. This observational study will measure the oxygenation properties of both chronically sun exposed and less sun exposed skin in the predefined groups of both young and older men and women.
Using selenium (Se) nanoparticles has received attention in recent years because of their therapeutic benefits due to their anticancer, antioxidant, anti-inflammatory, and anti-diabetic effects. This research was conducted to evaluate the possible protective impact of nano-Se on renal unilateral ischemia/reperfusion injury (uIRI) in adult male Wistar rats. Using clamping of the left renal pedicle within 45 min uIRI was induced. The animals were randomly divided into nine groups of control, nano-Se (0.25, 0.5, and 1 mg/kg bw/day) alone, uIRI control, and uIRI rats administrated with nano-Se. At 30 days after treatment, the animals were sacrificed to be assessed biochemically and histopathologically. Nano-Se in uIRI groups have significantly decreased serum creatinine, urea levels, renal histological damage, and increased antioxidant status. Also, our findings demonstrated that the administration of nano-Se caused a significant decrease in the immunoreactivity level of the epidermal growth factor (EGF) and EGFR expression (EGF receptor) in the renal tissue of the uIRI rats. Therefore, nano-Se possesses renoprotective effects, and this effect might be attributable to its antioxidant and free radical scavenger effects. These renoprotective effects may depend on the decreased EGF immunoreactivity level and EGFR expression in the kidney tissue and improve the structure of the kidney tissue. Thus, our research provided biochemical and histological data supporting the potential clinical use of nano-Se for the treatment of certain kidney disorders.
Flavopiridol 30 mg/m\^2 is given weekly for 4 weeks followed by a 2 week break for up to 6 cycles. It is given through a vein as a 30 minute infusion followed by a 4 hour infusion.
AIM: Less than a dozen cases of psoas abscesses in pregnancy have been described in the literature. We reviewed the literature when treating a patient with a psoas abscess after ipsilateral double J-ureteral stent placement (in the following: "double J-stent") due to infected hydronephrosis.
METHODS: In January 2022, this review was searched using the Pubmed/MEDLINE database and the mesh terms "Psoas Abscess" AND "Pregnancy". Studies were included in any language and of all years, describing a psoas abscess during pregnancy. When patients did not have a psoas abscess, the abscess occurred after pregnancy, or when there was no full text available, the article was excluded.
MAIN RESULTS: Ten case reports about patients with psoas abscesses during pregnancy were included. The classical symptomatic triad of psoas muscle abscess included lower back pain, limping and persistent fever with daily spikes. However, in most cases, not all three symptoms can be found. Especially, fever is absent in more than half of the patients. Psoas abscesses are described between 13 and 39 weeks of gestation. Primary psoas abscesses with haematogenous spread are more common during pregnancy than secondary with spread per continuitatem. In the literature, the main reasons for psoas abscess are spinal tuberculosis, drug abuse or underlying diseases such as Crohn's disease. It is not uncommon for the definite cause to be unclear. Regarding the patient's symptoms, pyelonephritis is often considered a possible aetiology. In general, the main treatment options include antibiotic treatment and abscess drainage. There is no higher caesarean section rate, and no negative outcome for the foetus has been described.
CASE PRESENTATION: In our patient, a 38-year-old obese Caucasian woman, who had received a left double J-stent for infected hydronephrosis at 15 weeks of gestation, we successfully treated a psoas abscess of 20 × 10 cm with a sonographically assisted abscess drainage and antibiotics. The further course of pregnancy and the elective repeat caesarean section at 38 + 0 weeks of gestation were without any problems. Double J-stent placement and laser stone lithotripsy during puerperium were performed because of recurrent urolithiasis.
CONCLUSIONS: Although rare, psoas abscesses can occur during pregnancy, and it has often been treated surgically in the past. A psoas abscess as a complication after infected hydronephrosis and intervention during pregnancy has never been reported in the literature. Even for obese patients, minimally invasive therapy may be a treatment option that has rarely been reported in the literature.
BACKGROUND: Deafness autosomal dominant 2A (DFNA2A) is related to non-syndromic genetic hearing impairment. The KCNQ4 (Potassium Voltage-Gated Channel Subfamily Q Member 4) can lead to DFNA2A. In this study, we report a case of autosomal dominant non-syndromic hearing loss with six family members as caused by a novel variant in the KCNQ4 gene.
METHODS: The whole-exome sequencing (WES) and pure tone audiometry were performed on the proband of the family. Sanger sequencing was conducted on family members to determine if the novel variant in the KCNQ4 gene was present. Evolutionary conservation analysis and computational tertiary structure protein prediction of the wild-type KCNQ4 protein and its variant were then performed. In addition, voltage-gated channel activity of the wild-type KCNQ4 protein and its variant were tested using whole-cell patch clamp.
RESULTS: It was observed that the proband had inherited autosomal dominant, non-syndromic sensorineural hearing loss as a trait. A novel co-segregating heterozygous missense variant (c.902C>A, p.Ala301Asp) of the KCNQ4 gene was identified in the proband and other five affected family members. This variant was predicted to cause an alanine-to-aspartic acid substitution at position 301 in the KCNQ4 protein. The alanine at position 301 is well conserved across different species. Whole-cell patch clamp showed that there was a significant difference between the WT protein currents and the mutant protein currents in the voltage-gated channel activity.
CONCLUSION: In the present study, performing WES in conjunction with Sanger sequencing enhanced the detection of a novel, potentially causative variant (c301 A>G; p.Ala301Asp) in exon 6 of the KCNQ4 gene. Therefore, our findings contributed to the mutation spectrum of the KCNQ4 gene and may be useful in the diagnosis and gene therapy of deafness autosomal dominant 2A.
Families recruited in Year 1 who are randomized to the wait-list group, and all families recruited in Year 2 will be assigned to the wait-list group. This group will receive the materials provided to all families, noted above, and the initial in-home assessment within 2 weeks of the screening to be conducted by a trained research assistant. At 1 year post-screening, the families in the wait-list group will be administered the follow-up assessment and will begin the Family Check-Up (FCU) intervention.
Maxillary sinus grafting is a predictable regenerative technique to facilitate maxillary posterior implant placement when there is insufficient vertical bone height inferior to the maxillary sinuses to allow placement of implants of adequate dimensions. It enables an increase in vertical bone height, which makes implant placement easier. Maxillary sinus mucosal membrane perforation is one of the most common intraoperative complications during maxillary sinus grafting and may result in extrusion of graft material into the sinus. When this occurs, the mucociliary function of the maxillary sinus may expel the extruded graft material through its natural ostium, though graft particles may remain in the sinus or possibly occlude the natural ostium. After grafting, transient maxillary sinus mucosal oedema may occur. A postoperative CBCT scan may reveal varying degrees of sinus opacification, namely partial, subtotal or total. Although it is always possible to identify graft material, which may enter the sinus as a result of membrane perforation that might not even be visible to the implantologist during the surgical procedure, it is challenging to assess whether sinus opacification is due to mucosal thickening or mucus accumulation. The aim of the present case series was to offer a pragmatic approach to managing asymptomatic patients whose CBCT scans demonstrated partial, subtotal or total maxillary sinus opacification with bone graft particles that seemed to have been extruded into the sinus.