anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
FIELD: organic chemistry. SUBSTANCE: invention relates to derivatives of saccharine of the general formula (I)   where L means O or N; when L means O then R 1  is 2,6-dichloro-3-[2-(4-morpholinyl)ethoxy] -benzoyl; when L means N then L together with R 1  means 4,5-di-(tert. -butylsulfonyl)-1,2,3-triazole-1-yl; R 2  is primary or secondary alkyl consisting of 2-4 carbon atoms; R 3  is lower alkoxy at any of 5-, 6- or 7-position, or their pharmaceutically acceptable acid or base additive salts which inhibit activity of proteolytic enzymes. Invention relates to pharmaceutical composition based on compounds of the formula (I)   exhibiting activity of elastase inhibitor also. EFFECT: improved method of synthesis, enhanced effectiveness of compounds as elastase inhibitors. 4 cl, 1 tbl
Volar plating has became as a standard approach for treating unstable distal radius fractures. The incidence of surgically treated patients with distal radius fractures has increased many fold from the beginning of this millennium, owing mostly to increased number of volar platings. The most striking increase of plate fixations has occurred in older patient groups, especially in females. With volar fixed-angle plate, very near-anatomic, stable fixation with relatively low complication rate, can be achieved even in osteoporotic bone. There are only few randomized, prospective studies comparing results of volar plating and conservative treatment, comparing patients aged over 65 years. Quite little is known of the results comparing conservative treatment and volar plating in patients aged below 65 years.

Main goal of our study was to compare the functional and radiological results of conservative treatment and volar fixed-angle plating in the management of distal radius fracture in patients aged over 50 years an older.
Who will receive 5 L/min oxygen flow through standard nasal cannula (gives FiO2 of about 0.4). The allocated flow rates will be maintained throughout the procedure unless intervention will be required at the discretion of the anesthesiologist in charge of the case.
BACKGROUND: The Mental Health Literacy Scale (MHLS) is a scale-based measure with 35 items that assesses various aspects of mental health literacy. The original English version was developed in Australia and has been translated into several languages. The present study aimed to translate and culturally adapt the questionnaire for its use in Germany and to determine the psychometric properties of the German version of the MHLS (MHLS-GER) in two different samples.
METHODS: After translation and cultural adaptation, the MHLS-GER was administered via an online survey in a general population sample and via a postal survey in patients with acute myocardial infarction (AMI). Exploratory factor analysis and confirmatory factor analysis were conducted to determine the dimensionality. Furthermore, internal consistency, known-groups-validity and measurement invariance were evaluated.
RESULTS: Data of 517 participants of the general population sample and 786 participants of the AMI sample were analyzed. In both samples a four-factor structure yielded good model fit indices. The four subscales of the MHLS-GER including 31 items comprise the topics 'knowledge' (11 items), 'information seeking' (4 items), 'stigmatization' (9 items) and 'social distance' (7 items). All four subscales showed good internal consistency (Cronbach's alpha: 0.80 to 0.90, average inter-item correlation: 0.30-0.59) and were mostly invariant across the two samples. Participants with previous experience with mental disorders (personal or professional context) showed higher scores on the four subscales.
CONCLUSION: In contrast to the unidimensional structure of the original version, the MHLS-GER comprises four subscales. All subscales showed acceptable to good psychometric properties and can now be used to assess mental health literacy. Further validation studies to evaluate test-retest-reliability and responsiveness are required.
No carcinogenicity studies have been conducted with eprosartan mesylate in combination with hydrochlorothiazide. Eprosartan mesylate was not carcinogenic in dietary restricted rats or ad libitum fed mice dosed at 600 mg and 2000 mg eprosartan/kg/day, respectively, for up to 2 years. In male and female rats, the systemic exposure (AUC) to unbound eprosartan at the dose evaluated was only approximately 25% of the exposure achieved in humans given TEVETEN® HCT. In mice, the systemic exposure (AUC) to unbound eprosartan was approximately 35 times the exposure achieved in humans given TEVETEN® HCT. Two-year feeding studies in mice and rats conducted under the auspices of the National Toxicology Program (NTP) uncovered no evidence of a carcinogenic potential of hydrochlorothiazide in female mice (at doses of up to approximately 600 mg/kg/day) or in male and female rats (at doses of up to approximately 100 mg/kg/day). The NTP, however, found equivocal evidence for hepatocarcinogenicity in male mice. Eprosartan mesylate was not mutagenic in vitro in mammalian cells (mouse lymphoma assay). Eprosartan mesylate alone or in combination with hydrochlorothiazide was not mutagenic in vitro in bacteria (Ames test) and did not cause structural chromosomal damage in vivo (mouse micronucleus assay). In human peripheral lymphocytes in vitro, eprosartan mesylate in combination with hydrochlorothiazide was positive for clastogenicity with and without metabolic activation. In the same assay, eprosartan mesylate alone was associated with polyploidy but there was only equivocal evidence of structural chromosomal damage. Hydrochlorothiazide was not genotoxic in vitro in the Ames test and in the Chinese Hamster Ovary (CHO) test for chromosomal aberrations, or in vivo in assays using mouse germinal cell chromosomes, Chinese hamster bone marrow chromosomes, and the Drosophila sex-linked recessive lethal trait gene. Positive test results were obtained in the in vitro CHO Sister Chromatid Exchange (clastogenicity) and Mouse Lymphoma Cell (mutagenicity) assays and in the Aspergillus nidulans non-disjunction assay. No fertility studies have been conducted with eprosartan mesylate in combination with hydrochlorothiazide. Eprosartan mesylate had no adverse effects on the reproductive performance of male or female rats at oral doses up to 1000 mg eprosartan/kg/day. Hydrochlorothiazide had no adverse effects on the fertility of mice and rats of either sex in studies wherein these species were exposed, via their diet, to doses of up to 100 and 4 mg/kg/day, respectively, prior to conception and throughout gestation.
Hemophilia A (HA) is an X-linked recessive genetic disease caused by mutations in the FVIII gene on the X chromosome, leading to abnormal coagulation function. In the male population, the incidence rate of hemophilia A was about 1/5000, and female patients with hemophilia A were extremely rare. Type A hemophilia patients mainly exhibit a tendency for bleeding, with a wide range of bleeding sites and frequent recurrence, which can form hematoma and joint deformation. This is an early phase 1, open-label, single-center, dose-escalation pilot trial to evaluate the safety and efficacy of a single intravenous infusion of NGGT003 in hemophilia A patients. 4-6 subjects will be enrolled and divided into 3 groups according to the principle of dose escalation, respectively administered intravenous infusion of NGGT003 at low dose (4e11vg/kg), medium dose (1e12vg/kg) and high dose (2.5e12vg/kg). All subjects will undergo 52 weeks of treatment observation and further 260 weeks of long-term follow-up.
BACKGROUNDMost humans have been infected with cytomegalovirus (CMV) by midlife without clinical signs of disease. However, in settings in which the immune system is undeveloped or compromised, the virus is not adequately controlled and consequently presents a major infectious cause of both congenital disease during pregnancy as well as opportunistic infection in children and adults. With clear evidence that risk to the fetus varies with gestational age at the time of primary maternal infection, further research on humoral responses to primary CMV infection during pregnancy is needed.METHODSHere, systems serology tools were applied to characterize antibody responses to CMV infection in pregnant and nonpregnant women experiencing either primary or chronic infection.RESULTSWhereas strikingly different antibody profiles were observed depending on infection status, limited differences were associated with pregnancy status. Beyond known differences in IgM responses used clinically for identification of primary infection, distinctions observed in IgA and FcγR-binding antibodies and among antigen specificities accurately predicted infection status. Machine learning was used to define the transition from primary to chronic states and predict time since infection with high accuracy. Humoral responses diverged over time in an antigen-specific manner, with IgG3 responses toward tegument decreasing over time as typical of viral infections, while those directed to pentamer and glycoprotein B were lower during acute and greatest during chronic infection.CONCLUSIONIn sum, this work provides insights into the antibody response associated with CMV infection status in the context of pregnancy, revealing aspects of humoral immunity that have the potential to improve CMV diagnostics.FUNDINGCYMAF consortium and NIH NIAID.
Participants will receive IVIG (intravenous immunoglobulin) 10g/d for 6 days. They also receive conventional liquid therapy and symptomatic supportive treatment.
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease, affecting 1 in 400 to 1000 individuals and accounting for 4% of end-stage renal disease in the United States and 8-10% in Europe. The condition is characterized by progressive development of kidney cysts with kidney enlargement and associated loss of kidney function. High blood pressure and cardiovascular disease are common in patients with ADPKD. Although the condition is often thought to affect primarily adults, it is clear that the disease can be present in the fetus and young children.

This study was designed to determine if treatment with the medicine pravastatin can slow the progression of kidney and heart disease when initiated early in life in patients with ADPKD. The Investigators will assess differences between pravastatin and placebo study groups over the three-year study period with respect to: 1) total kidney volume as assessed by magnetic resonance imaging (MRI); 2) left ventricular mass index as assessed by MRI; 3) urinary albumin excretion; and 4) endothelial-dependent vasodilation as assessed by brachial ultrasound. A total of 110 subjects were enrolled in this research study. This study involved pediatric subjects because the Investigators believe that early intervention is critical if they are to decrease the morbidity and mortality associated with this condition. If pravastatin is shown to be effective in ameliorating progression of renal and cardiovascular disease in this study, routine management of people with this condition will be drastically altered.
Regular breakfast eating NW and OW/OB children, 9-14 years of age, will participate in the experiment. Four isocaloric (450 kcal) breakfasts (eggs with a side of French fries, mashed potatoes, or beans, and control breakfast of milk, cereal and toast) and breakfast skipping will be examined. On five separate mornings, 7 days apart and after a 12 hour overnight fast, each participant will receive one of the four breakfasts or skip breakfast, in a randomized counterbalanced order. Participants will be given an ad libitum lunch 3 hours after breakfast and parents will report the rest of day food record for food intake analysis. Blood glucose will be measured via finger-prick at baseline, and 30, 60, 120, and 180 minutes after breakfast consumption. Subjective appetite will be measured with a visual analogue scale at baseline and every 15 minutes for 1 hour, and every hour for 3 hours.
Methadone is a mu-agonist opioid with an abuse liability similar to that of morphine and is a Schedule II controlled substance. Methadone, like morphine and other opioids used for analgesia, has the potential for being abused and is subject to criminal diversion.

Methadone can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing methadone hydrochloride tablets in situations where the clinician is concerned about an increased risk of misuse, abuse, or diversion.

Concerns about abuse, addiction, and diversion should not prevent the proper management of pain.

Healthcare professionals should contact their State Professional Licensing Board, or State Controlled Substances Authority for information on how to prevent and detect abuse or diversion of this product.
Sepsis is accompanied by a less-known mismatch between hemodynamics and mitochondrial respiration. We aimed to characterize the relationship and time dependency of microcirculatory and mitochondrial functions in a rodent model of intraabdominal sepsis. Fecal peritonitis was induced in rats, and multi-organ failure (MOF) was evaluated 12, 16, 20, 24 or 28 h later (n = 8/group, each) using rat-specific organ failure assessment (ROFA) scores. Ileal microcirculation (proportion of perfused microvessels (PPV), microvascular flow index (MFI) and heterogeneity index (HI)) was monitored by intravital video microscopy, and mitochondrial respiration (OxPhos) and outer membrane (mtOM) damage were measured with high-resolution respirometry. MOF progression was evidenced by increased ROFA scores; microcirculatory parameters followed a parallel time course from the 16th to 28th h. Mitochondrial dysfunction commenced with a 4-h time lag with signs of mtOM damage, which correlated significantly with PPV, while no correlation was found between HI and OxPhos. High diagnostic value was demonstrated for PPV, mtOM damage and lactate levels for predicting MOF. Our findings indicate insufficient splanchnic microcirculation to be a possible predictor for MOF that develops before the start of mitochondrial dysfunction. The adequate subcellular compensatory capacity suggests the presence of mitochondrial subpopulations with differing sensitivity to septic insults.
Coronavirus 2019 disease (COVID-19) is a deadly infection that causes a new type of severe acute respiratory syndrome. It has been reported that the mortality rate in critically ill patients with a diagnosis of COVID-19 reached 61%. The primary pathology in these patients is progressive hypoxia due to lung injury and associated multi-organ damage. It has been reported that aggressive treatments such as tracheal intubation and classical mechanical ventilation to treat lung injury are not helpful or even harmful. The highest mortality rate was reported as 86% in these patients on mechanical ventilation. Acute respiratory distress syndrome (ARDS) developing in COVID-19 infection is not typical and is estimated to have a different mechanism, therefore it is emphasized that different strategies should be used for the treatment of ARDS in these patients. Two of the most important strategies used in these patients followed in the intensive care unit are high flow nasal oxygenation (High Flow Nasal Oxygenation-HFNO) and non-invasive ventilation (Non-Invasive Ventilation-NIV). HFNO is a method frequently used before intubation in adult patients with acute respiratory failure. It is based on the principle of giving warm and humidified oxygen to the patient through a nasal cannula in the range of 1-70 L/min. Due to the low number of mechanical ventilators in many intensive care units at the beginning of the pandemic, it was used in many COVID-19 patients and was found to be effective in later retrospective analyzes. It has been reported in many studies that HFNO therapy is more effective than conventional mask oxygen therapy. There are publications stating that it is more advantageous compared to NIV as it is easier to apply and more comfortable for the patient. Conventional NIV is called continuous positive airway pressure (CPAP) or Bi-level positive airway pressure (BiPAP) ventilation. It is used as oxygen/ventilation therapy in SARS and H1N1 patients. Studies have reported that it is used in 70% of patients before tracheal intubation in COVID-19 patients. However, mortality was high in these patients.

HFNO and NIV strategies are the most commonly used strategies for the treatment of hypoxia in patients with a diagnosis of COVID-19 who are still followed in the intensive care unit, but there is no study comparing the two yet. In our prospective study, we aimed to compare these two treatment modalities. The primary goal is that the treatment is successful (weaned off HFNO/weaned off NIV: No need for HFNO or NIV and the patient recovers without the need for intubation). Failure will be evaluated as the need for intubation during treatment or the patient's death. Secondary aim is failure of treatment and discharge of patients from intensive care to service or home.
After Week 96, participants will continue to take their blinded study drug and attend visits every 12 weeks until the End of Blinded Treatment Visit. Following the End of Blinded Treatment Visit, participants in a country where B/F/TAF FDC is not available will be given the option to receive B/F/TAF FDC in an open-label extension phase for up to 48 weeks, or until the product becomes accessible through an access program, or until Gilead elects to discontinue the study in that country, whichever occurs first.
INTRODUCTION: Hearing loss (HL) has been associated with cognitive decline and dementia. We examined the temporal association between prevalent and incident HL and cognitive change.
METHODS: A total of 1823 participants (24-82 years) from the Maastricht Aging Study (MAAS) were assessed at baseline, 6 and 12 years, including pure-tone audiometry. Linear-mixed models were used to test the association between HL and cognition, adjusted for demographics and other dementia risk factors.
RESULTS: Participants with prevalent and incident HL showed a faster decline in verbal memory, information processing speed, and executive function than participants without HL. Decline was steady from baseline to 6 and 12 years for prevalent HL, but time-delayed from 6 to 12 years for incident HL. Having a hearing aid did not change associations.
DISCUSSION: Findings support the notion that HL is a risk factor for cognitive decline independent of other dementia risk factors. Onset of HL preceded onset of cognitive decline.
HIGHLIGHTS: We examined cognitive change in prevalent and incident hearing loss. Prevalent and incident hearing loss were associated with faster cognitive decline. For prevalent hearing loss, decline was steady from baseline to 6 and 12 years. Onset of hearing loss preceded the onset of cognitive decline. Having a hearing aid did not change the observed associations.
### Infusion in the Operating Room (OR) 

After administration of a recommended initial bolus dose of atracurium besylate injection (0.3 to 0.5 mg/kg), a diluted solution of atracurium besylate can be administered by continuous infusion to adults and pediatric patients aged 2 or more years for maintenance of neuromuscular block during extended surgical procedures. 

Infusion of atracurium should be individualized for each patient. The rate of administration should be adjusted according to the patient's response as determined by peripheral nerve stimulation. Accurate dosing is best achieved using a precision infusion device. 

Infusion of atracurium should be initiated only after early evidence of spontaneous recovery from the bolus dose. An initial infusion rate of 9 to 10 mcg/kg/min may be required to rapidly counteract the spontaneous recovery of neuromuscular function. Thereafter, a rate of 5 to 9 mcg/kg/min should be adequate to maintain continuous neuromuscular block in the range of 89% to 99% in most pediatric and adult patients under balanced anesthesia. Occasional patients may require infusion rates as low as 2 mcg/kg/min or as high as 15 mcg/kg/min. 

The neuromuscular blocking effect of atracurium administered by infusion is potentiated by enflurane or isoflurane and, to a lesser extent, by halothane. Reduction in the infusion rate of atracurium should, therefore, be considered for patients receiving inhalation anesthesia. The rate of atracurium infusion should be reduced by approximately one-third in the presence of steady-state enflurane or isoflurane anesthesia; smaller reductions should be considered in the presence of halothane. 

In patients undergoing cardiopulmonary bypass with induced hypothermia, the rate of infusion of atracurium required to maintain adequate surgical relaxation during hypothermia (25° to 28°C) has been shown to be approximately half the rate required during normothermia. 

Spontaneous recovery from neuromuscular block following discontinuation of atracurium infusion may be expected to proceed at a rate comparable to that following administration of a single bolus dose. 

### Infusion in the Intensive Care Unit (ICU) 

The principles for infusion of atracurium in the OR are also applicable to use in the ICU. 

An infusion rate of 11 to 13 mcg/kg/min (range: 4.5 to 29.5) should provide adequate neuromuscular block in adult patients in an ICU. Limited information suggests that infusion rates required for pediatric patients in the ICU may be higher than in adult patients. There may be wide interpatient variability in dosage requirements and these requirements may increase or decrease with time (see PRECAUTIONS, Long-Term Use in Intensive Care Unit (ICU)). Following recovery from neuromuscular block, readministration of a bolus dose may be necessary to quickly re-establish neuromuscular block prior to reinstitution of the infusion.
This document describes compositions and methods for inducing an immune response (e.g., a cellular response such as a cell-mediated cytolytic immune response) to a human papillomavirus (HPV) antigen, which can be displayed by HPV or exhibited by infected cells (e.g., cells from cervical and other tumors). The HPV protein can be joined to a stress protein by fusion (e.g., a recombinant fusion protein). Also described are expression vectors containing sequences encoding HPV antigens and stress proteins, which can be introduced into cells of a subject or cells ex vivo. Also described are compositions that include a stress protein linked to an HPV antigen and another pharmacologically acceptable component and stress protein-HPV antigen fusions and conjugates. These compositions can be used to induce or enhance an immune response against HPV and cells that exhibit HPV antigens, including HPV-associated tumors. The present invention also relates to function of these compounds.