anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Fatal or serious cases of hemorrhage have been reported in patients treated with Kyprolis [see Adverse Reactions (6.1)]. Hemorrhagic events have included gastrointestinal, pulmonary, and intracranial hemorrhage and epistaxis. The bleeding can be spontaneous and intracranial hemorrhage has occurred without trauma. Hemorrhage has been reported in patients having either low or normal platelet counts. Hemorrhage has also been reported in patients who were not on antiplatelet therapy or anticoagulation.

Promptly evaluate signs and symptoms of blood loss. Reduce or withhold dose as appropriate [see Dosage and Administration (2.3)].
FIELD: medicine, narcology, pharmacy. SUBSTANCE: invention relates to drug containing naltrexone and having additionally corticosteroids taken at the definite ratio of components. Triamcinolon is used preferably as corticosteroid and implantation form is used as medicinal form. Invention proposes also the method of treatment of patients with chronic alcoholism by stage effect on patients. Invention provides to increase number of patients with obtained remission and prolong remission period. EFFECT: enhanced effectiveness of treatment. 6 cl, 2 ex
Infants randomized to this arm will be monitored for a platelet transfusion threshold of 50 x 10\^9/L up to 7 days of life, and then for a platelet transfusion threshold of 35 x 10\^9/L at 7 or more days of life. Infants will remain on this protocol-driven threshold through 40 0/7 weeks postmenstrual age. The platelet dose will be 10 ml/kg administered over 60-120 minutes.
<P>PROBLEM TO BE SOLVED: To provide an expression system which provides heterologous proteins expressed by a non-native host organism but which have native-protein-like biological activity and/or structure.  <P>SOLUTION: An expression system provides heterologous proteins expressed by a non-native host organism but which have native-protein-like biological activity and/or structure. Disclosed are vectors, expression hosts and methods for expressing the heterologous proteins. The expression system involves co-expression of protein factor(s) which is/are capable of catalyzing disulphide bond formation and desired heterologous protein(s). The expression system is presented using yeast cells as the preferred host, protein disulphide isomerase (PDI) and thioredoxin (TRX) as the preferred examples of the protein factors and HCV-E2<SB>715</SB>envelope glycoprotein and human FIGF as the preferred examples of the heterologous proteins.  <P>COPYRIGHT: (C)2008,JPO&INPIT
INTRODUCTION: Intracranial hemorrhage (ICH) in functional neurosurgery is a relatively rare but serious complication. One of the possible risk factors related to ICH is the number of trajectories made for microelectrode recording (MER). Authors who solely rely on macrostimulation using macroelectrodes argue that the incidence of ICH is much lower while maintaining good clinical efficacy of deep brain stimulation (DBS). The present study aimed to assess the incidence of ICH in DBS procedures by reducing to the minimum the number of brain passes and the diameter of guiding cannulas. For this reason, we used one MER guiding cannula exclusively for track making with subsequent macrostimulation done through the implanted DBS electrode.
MATERIAL AND METHODS: All DBS procedures performed between January 2018 and January 2022 in the Department of Neurosurgery of the Institute of Psychiatry and Neurology in Warsaw were analyzed for possible ICH and other perioperative complications. The DBS lead was implanted by an MR image-guided and intraprocedural CT-verified approach. No MER was done.
RESULTS: During four years 191 patients underwent 267 DBS lead implantations in 252 stereotactic procedures. ICH occurred in 2 patients. Both were symptomatic. Adverse symptoms resolved within a week. Two DBS leads required replacement. There was 1 case of hematoma at the implantable pulse generator (IPG) site and 1 case of pneumothorax due to tunneling of the extension.
CONCLUSIONS: Our surgical technique has a low incidence of ICH. Symptomatic ICH affected 2 patients. The other perioperative complications mentioned above required repeated surgery or conservative treatment. No patient suffered from permanent deficits.
Hyperexcitability of neuronal networks is central to the pathogenesis of Alzheimer's disease (AD). Pharmacological activation of Kv7 channels is an effective way to reduce neuronal firing. Our results showed that that pharmacologically activating the Kv7 channel with Retigabine (RTG) can alleviate cognitive impairment in mice without affecting spontaneous activity. RTG could also ameliorate damage to the Nissl bodies in cortex and hippocampal CA and DG regions in 9-month-old APP/PS1 mice. Additionally, RTG could reduce the Aβ plaque number in the hippocampus and cortex of both 6-month-old and 9-month-old mice. By recordings of electroencephalogram, we showed that a decrease in the number of abnormal discharges in the brains of the AD model mice when the Kv7 channel was opened. Moreover, Western blot analysis revealed a reduction in the expression of the p-Tau protein in both the hippocampus and cortex upon Kv7 channel opening. These findings suggest that Kv7 channel opener RTG may ameliorate cognitive impairment in AD, most likely by reducing brain excitability.
The voltage-gated sodium channel Na V 1.7 is an essential component of human pain signaling. Changes in Na V 1.7 trafficking are considered critical in the development of neuropathic pain. SUMOylation of collapsin response mediator protein 2 (CRMP2) regulates the membrane trafficking and function of Na V 1.7. Enhanced CRMP2 SUMOylation in neuropathic pain correlates with increased Na V 1.7 activity. Pharmacological and genetic interventions that interfere with CRMP2 SUMOylation in rodents with neuropathic pain have been shown to reverse mechanical allodynia. Sentrin or SUMO-specific proteases (SENPs) are vital for balancing SUMOylation and deSUMOylation of substrates. Overexpression of SENP1 and/or SENP2 in CRMP2-expressing cells results in increased deSUMOylation and decreased membrane expression and currents of Na V 1.7. Although SENP1 is present in the spinal cord and dorsal root ganglia, its role in regulating Na V 1.7 function and pain is not known. We hypothesized that favoring SENP1 expression can enhance CRMP2 deSUMOylation to modulate Na V 1.7 channels. In this study, we used a clustered regularly interspaced short palindromic repeats activation (CRISPRa) SENP1 lentivirus to overexpress SENP1 in dorsal root ganglia neurons. We found that SENP1 lentivirus reduced CRMP2 SUMOylation, Na V 1.7-CRMP2 interaction, and Na V 1.7 membrane expression. SENP1 overexpression decreased Na V 1.7 currents through clathrin-mediated endocytosis, directly linked to CRMP2 deSUMOylation. Moreover, enhancing SENP1 expression did not affect the activity of TRPV1 channels or voltage-gated calcium and potassium channels. Intrathecal injection of CRISPRa SENP1 lentivirus reversed mechanical allodynia in male and female rats with spinal nerve injury. These results provide evidence that the pain-regulating effects of SENP1 overexpression involve, in part, the modulation of Na V 1.7 channels through the indirect mechanism of CRMP2 deSUMOylation.
BACKGROUND: Police officers are at a high risk of noise-induced hearing loss (NIHL) owing to the nature of their work. Therefore, this study aimed to compare the risk of NIHL in police officers and controls.
METHODS: This study used the National Health Insurance claims data of workers aged 25-65 years obtained from 2005 to 2015. The case group comprised police officers, while the control group comprised general workers and public officers. The study followed a three-phase cohort design. The standardized incidence ratio (SIR) was calculated using an indirect standardization method based on age. Propensity score matching was performed using the greedy matching method, with a police officer-to-control group ratio of 1:3. Cox regression analysis was performed for each matched control group. Statistical significance was determined by a lower limit of greater than 1, based on the 95% confidence interval (CI).
RESULTS: The SIR values for police officers were 1.62 (95% CI: 1.44-1.82) compared with general workers and 1.78 (95% CI: 1.66-1.73) compared with public officers. Police officers exhibited an increased risk of NIHL compared with general workers (hazard ratio (HR): 1.71, 95% CI: 1.49-1.98) and public officers (HR: 2.19, 95% CI: 1.88-2.56).
CONCLUSIONS: It is necessary to prevent NIHL by reducing occupational noise exposure through measures such as wearing earplugs, improving shooting training methods, and improving the shift work system.
Introduction: Despite the importance of an adequate peak inspiratory flow (PIF) during inhaled therapy in patients with COPD, the available evidence in patients with severe exacerbations and their evolution after admission is limited. We conducted this study to evaluate the PIF during an exacerbation, its variability, and predictors of suboptimal PIF. Material and Methods: A prospective study that included patients admitted for COPD exacerbation. Clinical, demographic, and functional variables were recorded. Using the In-Check DIAL G16®, PIF without resistance (PIF-nr) and that obtained by simulating the resistance of the patients' usual inhalers (PIF) were determined within the first 48 hours of admission and prior to discharge; also assessed during a stable phase in a subgroup of patients. The results were compared and, through a multivariate study, the factors related to a suboptimal PIF were analyzed. Results: A total of 137 patients were included; 27% were women and the mean age was 69.4 ± 9.8 years. Moreover, 30.8% of the participants with dry powder inhalers had a suboptimal PIF at admission and it was independently associated with female sex (odds ratio [OR] = 8.635; 95% confidence interval [CI] [2.007, 37.152]; p < 0.01) and forced expiratory volume in the 1st second (FEV1) (OR = 0.997; 95% CI: [0.995, 0.999]; p = 0.04). At discharge, suboptimal PIF reduced to 17% (p < 0.01). PIF-nr increased from the time of admission to the stable phase. Conclusion: One third of COPD patients admitted with a severe exacerbation had a suboptimal PIF, being female sex and lower FEV1 independent predictors. PIF-nr improved progressively after the exacerbation.
The incidence of atherosclerotic cardiovascular disease in women does not approach rates seen in men until approximately a decade following menopause, suggesting that estrogen is vasculoprotective. Infectious pathogens such a Chlamydia pneumoniae (C. pneumoniae) and human cytomegalovirus (hCMV) have been implicated in the pathogenesis of atherosclerosis. Experimental studies in cultured lymphocytes and animals suggest that estrogen stimulates cell-mediated immune responsiveness, observations that are potentially relevant to the eradication of intracellular pathogens including C. pneumoniae and hCMV. The purpose of this study is to determine whether estrogen therapy augments cell-mediated immune responsiveness in estrogen-deficient postmenopausal women who have serologic evidence of chronic infection with C. pneumoniae and/or hCMV. A comparison will be made between seropositive and seronegative women. We propose that estrogen therapy will stimulate a more efficient cell-mediated response to these chronically persistent infectious intracellular pathogens, resulting in eradication of these organisms that are of potential importance in atherogenesis.
IMPORTANCE: Over the past 2 decades, systemic therapy for early-stage breast cancer has gradually moved from the adjuvant to the neoadjuvant setting. Administration of systemic therapy before surgery leads to potential improvements in surgical outcomes and allows for the assessment of the pathologic response to treatment. For patients with residual disease (RD), 3 adjuvant strategies have been shown to improve outcomes: (1) adjuvant trastuzumab emtansine for ERBB2-positive disease, (2) adjuvant capecitabine for triple-negative disease, and (3) adjuvant olaparib for patients with germline BRCA variants. Furthermore, studies are testing novel drugs in the postneoadjuvant setting. Given the potential to tailor adjuvant therapy based on the response to preoperative systemic therapy, recognizing the complexities of response to neoadjuvant therapy and moving beyond the binary paradigm of RD vs experiencing a pathologic complete response is becoming increasingly necessary.
OBSERVATIONS: Novel antibody-drug conjugates, anti-ERBB2 tyrosine kinase inhibitors, and immune checkpoint inhibitors are being evaluated as additional rescue options in phase 3 trials for patients with RD after neoadjuvant treatment. Concomitantly, the prognostic role of RD has been refined by the introduction of the residual cancer burden. In addition, the genomic landscape of RD has been found to be associated with long-term prognosis, as has the immune background of the disease evaluated via the presence of tumor-infiltrating lymphocytes. Lastly, the dynamics of circulating tumor DNA may allow for further improvement in prognostication by understanding which patients harbor detectable minimal RD.
CONCLUSIONS AND RELEVANCE: Escalating adjuvant treatment has led to meaningful survival improvements among patients with breast cancer and RD after neoadjuvant therapy. Uncovering the anatomic and biological intricacies of RD will allow for increased precision in postneoadjuvant treatments, moving beyond the binary paradigm of RD vs pathologic complete response, toward more tailored rescue strategies in the adjuvant setting.
Participants will first receive a single dose of ALXN1840 test formulation on Day 1 of Period 1. After a washout period of 14 days, they will then receive a single dose of ALXN1840 reference formulation on Day 1 of Period 2.
BACKGROUND: The European hedgehog (Erinaceus europaeus) is known for high levels of ectoparasitism that not only represents a health risk for the animals themselves, but also for pet animals and humans as hedgehogs are frequently taken into human care. In the present study, patterns of ectoparasite infestation were assessed in hedgehogs taken into care at northern German animal rehabilitation centres.
METHODS: Ectoparasites (ticks, fleas and mites) of 498 hedgehogs were collected over a period of 3 years from July 2018 to May 2021. Species were identified based on morphological characteristics and also via amplification and sequencing of the partial cytochrome c oxidase subunit 2 (COX-2) gene for fleas of the family Ceratophyllidae. Seasonal changes in infestation patterns as well as correlations with animal age, body weight and health status were assessed using generalised linear models.
RESULTS: Infestation with ticks, fleas and mites occurred throughout the year. Overall, 86.5% (431/498) of the examined hedgehogs were infested with ticks, 91.4% (455/498) with fleas and 17.7% (88/498) with mites. Ixodes ricinus and Ixodes hexagonus/Ixodes canisuga were the most common tick species detected, with the additional occurrence of one Ixodes frontalis. Significant seasonal changes were observed for I. ricinus, but not for I. hexagonus/I. canisuga. Additionally, I. ricinus nymph prevalence declined significantly as of 2020, probably as a consequence of the climate change-related drought as of 2018. In hedgehogs with flea infestations, Archaeopsylla erinacei, Ceratophyllus sciurorum, Nosopsyllus fasciatus and Ctenocephalides felis were identified. In all cases of mite infestation, Caparinia tripilis was detected, in addition to specimens of the family Macronyssidae and free-living mites of the family Acaridae. Statistical analyses showed correlations regarding the factors month, year, body weight and age, but no correlation was evident regarding the health status of the animals.
CONCLUSIONS: With a detected infestation rate of 98.6%, almost all of the examined hedgehogs were infested with at least one ectoparasite species. The seasonal activity patterns of the different ectoparasite species together with the complex annual cycle of hedgehogs lead to different seasonal patterns in ectoparasite prevalence and infestation intensities. Due to the risk of transmission of zoonotic pathogens as well as the possible negative impact on the host itself, hedgehogs should be treated against ectoparasites when taken into care facilities.
Participants will be instructed to consume a bottle of the ketone monoester (KME) supplement, containing the KME of β-hydroxybutyrate (β-OHB), 15-min prior to each meal (3x/day) for 14 days. This dosing protocol raises plasma β-OHB consistently during the waking hours. Oral KME will be provided in opaque bottles labelled A or B to maintain condition blinding. Each bottle will contain a drink providing 15g of a KME supplement: \[R\]-3-hydroxybutyl \[R\]-3-hydroxybutyrate (ΔG®, TDeltaS, Oxford, UK).
Patients with recurrent and/or metastatic unresectable Head and Neck Cancer have a poor prognosis and limited treatment options. Pembrolizumab and Nivolumab, both ICIs (Immune Checkpoint Inhibitors), are approved therapies for this condition. However, no approved treatment options exist for patients who progress on ICI therapies. Hence, there is an unmet medical need post-failure of ICI therapy. NRC-2694-A is an orally administered small-molecule tyrosine kinase inhibitor. It was discovered and developed by NATCO Pharma Ltd. NRC-2694-A demonstrated response in HNSCC patients in a Phase-I study as a monotherapy. This was further substantiated in a Phase-II study in combination with cisplatin/carboplatin and paclitaxel.
Participants in the mindfulness-based intervention arm will receive 12 weekly sessions of 2 to 2.5 hours duration. The intervention will be delivered in a group format. Participants will be assigned weekly homework.
The present invention relates to an anti-oxidant, anti-inflammatory, and skin whitening composition. According to the present invention, toosendanin inhibits generation of free radicals and thus has an anti-oxidant effect. In addition, toosendanin inhibits generation of NO and thus has an anti-inflammatory effect. Toosendanin inhibits synthesis of melanin and thus has a skin whitening effect. Therefore, the composition can be used as a pharmaceutical composition, an external use skin formulation, a cosmetic composition, or health food. The composition includes a compound represented by chemical formula 1 as an active ingredient.
Participants with disease other than relapsed/refractory follicular lymphoma (FL), non-FL B-cell non-Hodgkin's lymphoma (B-NHL), or mantle cell Lymphoma (MCL), as assessed by the Independent Central Pathological Committee, received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol. This group was created to include participants who enrolled, but whose later diagnoses by the Independent Central Pathological Committee excluded them from analysis in the FL and non-FL B-NHL/MCL groups because they had different disease than those prespecified in the protocol.
Study participants in the control arm will be offered complementary attendance in the Health Tech Junior enterostomy and vascular access competency based training course while awaiting their session. This is being done to minimize the potential confound of generalized improvements in self-efficacy that may occur as a result of participating in an 8 hour learning opportunity at SickKids. The control group will also complete the tracheostomy course during session 3 and 4 but this will occur outside the window of data collection for the study procedures. Data collection intervals as described above for the intervention group will be followed for the control group.
N-methyl-D-aspartate receptors (NMDARs) are a subtype of ionotropic glutamate receptors critical for synaptic transmission and plasticity, and for the development of neural circuits. Rare or de-novo variants in GRIN genes encoding NMDAR subunits have been associated with neurodevelopmental disorders characterized by intellectual disability, developmental delay, autism, schizophrenia, or epilepsy. In recent years, some disease-associated variants in GRIN genes have been characterized using recombinant receptors expressed in non-neuronal cells, and a few variants have also been studied in neuronal preparations or animal models. Here we review the current literature on the functional evaluation of human disease-associated variants in GRIN1, GRIN2A and GRIN2B genes at all levels of analysis. Focusing on the impact of different patient variants at the level of receptor function, we discuss effects on receptor agonist and co-agonist affinity, channel open probability, and receptor cell surface expression. We consider how such receptor-level functional information may be used to classify variants as gain-of-function or loss-of-function, and discuss the limitations of this classification at the synaptic, cellular, or system level. Together this work by many laboratories worldwide yields valuable insights into NMDAR structure and function, and represents significant progress in the effort to understand and treat GRIN disorders. Keywords: NMDA receptor , GRIN genes, Genetic variants, Electrophysiology, Synapse, Animal models.
A system comprising a holding area, a manual section, a distribution section, and at least one conveyor. The manual section may include a handling area enabled for pill counting, pharmacist verification, exception handling, or combinations thereof. The distribution section may be disposed proximate the handling area and the manual section, and may include a robot and a scanner. The at least one conveyor may enable transportation of a container between said distribution section and said manual section. The robot may be adapted to pick a container from the holding area and move the container to the scanner for scanning. The robot may also be further adapted to place the container onto the conveyor to direct the container to a handling area which is enabled for an action based on the scan.
A detergent containing (A) one or more selected from the group consisting of carbobetaine amphoteric surfactants (A1) and nonionic surfactants (A2) and (B) a quaternary ammonium cation-modified silicone represented by general formula (1), the mass ratio [(A)/(B)] of component (A) and component (B) being 0.1-1000 inclusive and the content of anionic surfactants being 4 mass% or lower. [In formula (1), R 11  represents a C1-6 hydrocarbon group. R 12  represents a hydrogen atom, a C1-20 hydrocarbon group, or a C1-20 hydrocarbon group that includes an amide bond. R 13  represents a C1-20 hydrocarbon group or a C1-20 hydrocarbon group that includes an amide bond. L represents a divalent organic group. Q -  represents a counter ion of a quaternary ammonium ion. R represents a number of 2 or higher. Multiple R 11  and R 12  may be the same or different. And, the bonding form may be block or random, regardless of the bonding order of structural units within parentheses.]