anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
BACKGROUND AND PURPOSE: Morphine is important for treatment of acute and chronic pain. However, there is high interpatient variability and often inadequate pain relief and adverse effects. To better understand variability in the dose-effect relationships of morphine, we investigated the effects of its non-linear blood-brain barrier (BBB) transport on μ-receptor occupancy in different CNS locations, in conjunction with its main metabolites that bind to the same receptor.
EXPERIMENTAL APPROACH: CNS exposure profiles for morphine, M3G and M6G for clinically relevant dosing regimens based on intravenous, oral immediate- and extended-release formulations were generated using a physiology-based pharmacokinetic model of the CNS, with non-linear BBB transport of morphine. The simulated CNS exposure profiles were then used to derive corresponding μ-receptor occupancies at multiple CNS pain matrix locations.
KEY RESULTS: Simulated CNS exposure profiles for morphine, M3G and M6G, associated with non-linear BBB transport of morphine resulted in varying μ-receptor occupancies between different dose regimens, formulations and CNS locations. At lower doses, the μ-receptor occupancy of morphine was relatively higher than at higher doses of morphine, due to the relative contribution of M3G and M6G. At such higher doses, M6G showed higher occupancy than morphine, whereas M3G occupancy was low throughout the dose ranges.
CONCLUSION AND IMPLICATIONS: Non-linear BBB transport of morphine affects the μ-receptor occupancy ratios of morphine with its metabolites, depending on dose and route of administration, and CNS location. These predictions need validation in animal or clinical experiments, to understand the clinical implications.
Effectively assessing oxygen delivery and demand is one of the key targets for fluid resuscitation in sepsis. Clinical signs and symptoms, blood lactic acid levels, and mixed venous oxygen saturation (SvO2) or central venous oxygen saturation (ScvO2) all have their limitations. In recent years, these limitations have been overcome through the use of derived indicators from carbon dioxide (CO2) such as mixed veno-arterial carbon dioxide partial pressure difference (Pv-aCO2, PCO2 gap, or ΔPCO2), the ratio of mixed veno-arterial carbon dioxide partial pressure difference to arterial-mixed venous oxygen content difference (Pv-aCO2/Ca-vO2). Pv-aCO2, PCO2 gap or ΔPCO2 is not a purely anaerobic metabolism indicator as it is influenced by oxygen consumption. However, it reliably indicates whether blood flow is sufficient to carry CO2 from peripheral tissues to the lungs for clearance, thus reflecting the adequacy of cardiac output and metabolism. The Pv-aCO2/Ca-vO2 may serve as a marker of hypoxia. SvO2 and ScvO2 represent venous oxygen saturation, reflecting tissue oxygen utilization. When oxygen delivery decreases but tissues still require more oxygen, oxygen extraction rate usually increases to meet tissue demands, resulting in decreased SvO2 and ScvO2. But in some cases, even if the oxygen delivery rate and tissue utilization rate of oxygen are reduced, it may still lead to a decrease in SvO2 and ScvO2. Sepsis is a classic example where tissue oxygen utilization decreases due to factors such as microcirculatory dysfunction, even when oxygen delivery is sufficient, leading to decrease in SvO2 and ScvO2. Additionally, the solubility of CO2 in plasma is approximately 20 times that of oxygen. Therefore, during sepsis or septic shock, derived variables of CO2 may serve as sensitive markers for monitoring tissue perfusion and microcirculatory hemodynamics. Its main advantage over blood lactic acid is its ability to rapidly change and provide real-time monitoring of tissue hypoxia. This review aims to demonstrate the principles of CO2-derived variables in sepsis, assess the available techniques for evaluating CO2-derived variables during the sepsis process, and discuss their clinical relevance.
AIMS: (1) To use intraoperative photographs to visualize and explain pudendal nerve compressions and anatomical variations of compression sites in patients with chronic pelvic pain. (2) To emphasize the diagnostic importance of sensory examination with a safety pin at the six pudendal nerve branches in all patients with chronic pelvic pain; the dorsal nerves (penis or clitoris; the perineal nerves; and the inferior rectal nerves).
METHODS: Between 2003 and 2014, "definite" pudendal neuropathy was diagnosed by examination and with two neurophysiologic tests. Neurolysis, via a transgluteal approach, was recommended only after 14 weeks of conservative care failed to adequately improve symptoms and validated symptom scores. Photographs of surgical findings were culled for their educational impact. An illustration of each photo clarifies the surgical anatomy.
RESULTS: The transgluteal incision permits access to pudendal anatomy and compression sites from the subpiriformis area through the interligamentary space and the pudendal canal (Alcock canal). Compressions were acquired or congenital and severity varied significantly. Pinprick sensory testing diagnoses pudendal neuropathy in 92% of both genders. Mid-nerve compression occurred commonly between the sacrotuberous and sacrospinous ligaments less frequently in the Alcock canal, but also at aberrant pathways, for example, between layers of the sacrotuberous ligament; a separate inferior rectal nerve passing through the sacrospinous ligament; at an anomalous lateral pathway posterior to the ischial spine. The results of international surgeons are discussed.
CONCLUSIONS: Decompression surgery was recommended in approximately 35% of patients in this practice, when pudendal neuropathy (pudendal syndrome), did not respond to two conservative levels of treatment: (1) nerve protection and medications and, (2) a series of three pudendal nerve perineural injections given at 4-week intervals. Significant nerve compression is consistently observed. Pathophysiology includes axonopathy from ischemia and demyelination. Neuropathy is readily diagnosed using a pinprick sensory examination of six pudendal nerve branches. Monitoring with the National Institutes of Health Chronic Prostatitis Symptom Index records cures >13 years.
Caspase-4 (CASP4) is a member of the inflammatory caspase subfamily and promotes inflammation. Here, we report that CASP4 in lung adenocarcinoma cells contributes to both tumor progression via angiogenesis and tumor hyperkinesis and tumor cell killing in response to high interferon (IFN)-γ levels. We observe that elevated CASP4 expression in the primary tumor is associated with cancer progression in patients with lung adenocarcinoma. Further, CASP4 knockout attenuates tumor angiogenesis and metastasis in subcutaneous tumor mouse models. CASP4 enhances the expression of genes associated with angiogenesis and cell migration in lung adenocarcinoma cell lines through nuclear factor kappa-light chain-enhancer of activated B cell signaling without stimulation by lipopolysaccharide or tumor necrosis factor. CASP4 is induced by endoplasmic reticulum stress or IFN-γ via signal transducer and activator of transcription 1. Most notably, lung adenocarcinoma cells with high CASP4 expression are more prone to IFN-γ-induced pyroptosis than those with low CASP4 expression. Our findings indicate that the CASP4 level in primary lung adenocarcinoma can predict metastasis and responsiveness to high-dose IFN-γ therapy due to cancer cell pyroptosis.
Carcinogenicity studies with docetaxel have not been performed.

Docetaxel was genotoxic by an aneugenic mechanism in the in vitro chromosome aberration test in CHO-K1 cells and in the in vivo micronucleus test in mice administered doses of 0.39 to 1.56 mg/kg (about 1/60 th to 1/15 th the recommended human dose on a mg/m 2 basis). Docetaxel was not mutagenic in the Ames test or the CHO/HGPRT gene mutation assays. 

Docetaxel did not reduce fertility in rats when administered in multiple intravenous doses of up to 0.3 mg/kg (about 1/50 th the recommended human dose on a mg/m 2 basis), but decreased testicular weights were reported. This correlates with findings of a 10-cycle toxicity study (dosing once every 21 days for 6 months) in rats and dogs in which testicular atrophy or degeneration was observed at intravenous doses of 5 mg/kg in rats and 0.375 mg/kg in dogs (about 1/3 rd and 1/15 th the recommended human dose on a mg/m 2 basis, respectively). An increased frequency of dosing in rats produced similar effects at lower dose levels.
PURPOSE:To obtain the sharp tomographic image of a specimen with high sensitivity, by detecting a noise signal in such a state that magnetic field gradients in X-axis and Y-axis directions are superposed to the time zone between pulses 90-180 deg. to a NMR static magnetic field. CONSTITUTION:The magnetic field gradient 6 in an X-axis direction, the magnetic field gradient 7 in a Y-axis direction and the magnetic field gradient 8 in a Z-axis direction are superposed to a static magnetic field between a 90 deg. pulse 1 and a 180 deg. pulse 2. The spin in the specific cross-sectional layer in a specimen excited by the pulse 1 is disturbed in its phase and not detected as a signal and only a noise signal component is detected. This noise signal component also contains the NMR signal obtained by repeating a NMR signal exciting/detecting sequence preceding to a NMR noise signal exciting/detecting sequence. Therefore, by subtracting the noise signal component from said signal, the noise signal causing the linear noise image in the longitudinal direction is removed and a sharp tomographic signal can be obtained.
The invention relates to a synbiotic (probiotic and prebiotic) for human purposes which is administered as additive to the food of people for well intended favorable effect on their health. The synbiotic comprises a mixture of monocultures Lactobacillus acidophilus N 180, N NBIMCC 8242, Lactobacillus helveticus N 173, N NBIMCC 8268, Lactobacillus helveticus N 179, Lactobacillus delbrueckii subsp.Lactis N 182, NBIMCC 8250, Lactobacillus debrueckii subsp. Bulgaricus N 186, N NBIMCC 8243, Lactobacillus debrueckii subsp. Bulgaricus N 190, N NBIMCC 8247, Streptococcus thermophilus N 205, N NBIMCC8253, Bifidobacterium bifidum N PB-b1, N NBIMCC 8328 and Bifidobacterium longum NPB-b3, N NBIMCC 8329. The newly isolated strains of lactic acid bacteria and bifidobacteria individually and together have the highest probiotic effect, have good survival in acid medium, separate considerable amount of bacteriocines, which inhibit the total amount of the conditionally pathogenic microorganisms in the gastrointestinal tract. The components of the synbiotic mutually ensure optimum conditions for retention in the mucous membrane and the development and propagation of cultures. Its composition is rich in indispensable amino acids and biologically active substances, which promote the general health status of the organism.
<P>PROBLEM TO BE SOLVED: To provide a new, safe and effective treatment of pain by targeting a low molecular mediator or exacerbator of the pain, such as an NGF.  <P>SOLUTION: This NGF function-neutralizing antibody is provided by interacting or binding with a human nerve growth factor (NGF) and thereby neutralizing the function of the NGF. The method for neutralizing the function of the NGF and especially for treating NGF-associated disorders (e.g. chronic pain) is provided by administering the pharmaceutically effective amount of a pharmaceutical composition of such the antibody, and of the anti-NGF antibody. The method for deciding the amount of the NGF in a sample by using the anti-NGF antibody is also provided.  <P>COPYRIGHT: (C)2010,JPO&INPIT
Participants will apply (under supervision) a pea-sized dose of dentifrice containing Dentifrice containing 0.76% sodium monofluorophosphate (1000ppm fluoride)to each of the two qualifying teeth using their finger by direct application and gently rubbing into the tooth's cervical margin for the allocated time. No rinsing will be permitted.
Participants will receive DF-003 once daily by oral administration for 14 days. The specific doses given will be based on data collected in Part 1 of the study. This part of the study may include 1 mg, 5 mg, or 25 mg capsules.
Cardiovascular disease (CVD) is a leading cause of death in chronic kidney disease (CKD). Hemodialysis is one of the main treatments for patients with end-stage kidney disease. Epidemiological data has shown that acute myocardial infarction (AMI) accounts for the main reason for death in patients with CKD under hemodialysis therapy. Immune dysfunction and changes in metabolism (including a high level of inflammatory cytokines, a disorder of lipid and mineral ion homeostasis, accumulation of uremic toxins et al.) during CKD can deteriorate stability of atherosclerotic plaque and promote vascular calcification, which are exactly the pathophysiological mechanisms underlying the occurrence of AMI. Meanwhile, the hemodialysis itself also has adverse effects on lipoprotein, the immune system and hemodynamics, which contribute to the high incidence of AMI in these patients. This review aims to summarize the mechanisms and further promising methods of prevention and treatment of AMI in CKD patients undergoing hemodialysis, which can provide an excellent paradigm for exploring the crosstalk between the kidney and cardiovascular system.
Specific aim 1: To perform a pilot and feasibility study of disseminating current knowledge of readmission prevention in cirrhosis by using the Patient Buddy App with patient and caregiver interfaces. Eighty subjects (40 cirrhotic inpatients and 40 caregivers) will be enrolled and trained on the Patient Buddy at discharge. The App focuses on daily communication between patient/caregivers and the study team based on previously identified risk factors associated with readmission. The study team will initiate measures to prevent readmission using these communications. A detailed analysis of 30-day readmissions and input of the patients,caregivers and nurse manager will be performed to improve the App. Avoidable readmissions will be defined by a committee of hepatologists who is not part of the study at VCU.

Specific aim 2: To incorporate the opinion of key stakeholders (patients, caregivers and case managers) towards improving the Patient Buddy App in the prevention of avoidable readmission in cirrhosis. The input of the key stakeholders and the analysis of readmissions prevented during the pilot study will be used to update the App for preventing avoidable readmissions in future studies
BACKGROUND: Changes in arterial partial pressure of carbon dioxide (Pa co2 ) may alter cerebral perfusion in critically ill patients with acute brain injury. Consequently, international guidelines recommend normocapnia in mechanically ventilated patients with acute brain injury. The measurement of end-tidal capnography (Et co2 ) allows its approximation. Our objective was to report the agreement between trends in Et co2 and Pa co2 during mechanical ventilation in patients with acute brain injury.
METHODS: Retrospective monocenter study was conducted for 2 years. Critically ill patients with acute brain injury who required mechanical ventilation with continuous Et co2 monitoring and with 2 or more arterial gas were included. The agreement was evaluated according to the Bland and Altman analysis for repeated measurements with calculation of bias, and upper and lower limits of agreement. The directional concordance rate of changes between Et co2 and Pa co2 was evaluated with a 4-quadrant plot. A polar plot analysis was performed using the Critchley methods.
RESULTS: We analyzed the data of 255 patients with a total of 3923 paired ΔEt co2 and ΔPa co2 (9 values per patient in median). Mean bias by Bland and Altman analysis was -8.1 (95 CI, -7.9 to -8.3) mm Hg. The directional concordance rate between Et co2 and Pa co2 was 55.8%. The mean radial bias by polar plot analysis was -4.4° (95% CI, -5.5 to -3.3) with radial limit of agreement (LOA) of ±62.8° with radial LOA 95% CI of ±1.9°.
CONCLUSIONS: Our results question the performance of trending ability of Et co2 to track changes in Pa co2 in a population of critically ill patients with acute brain injury. Changes in Et co2 largely failed to follow changes in Pa co2 in both direction (ie, low concordance rate) and magnitude (ie, large radial LOA). These results need to be confirmed in prospective studies to minimize the risk of bias.
BACKGROUND: In this study, we tested the null hypothesis that robotic-assisted total hip arthroplasty (THA) vs conventional THA was not associated with (1) the amount of postoperative opioid use and (2) the incidence of new, persistent opioid use.
MATERIALS AND METHODS: We used a large, national administrative database to identify patients 50 years and older undergoing primary robotic or conventional THA. Patients with hip fractures or a history of malignancy, hip infection, or opioid use disorder were excluded. Patients who filled an opioid prescription within 1 year to 30 days preoperatively or who underwent a subsequent procedure within 1 year after THA were excluded. Outcomes included the morphine milligram equivalents (MMEs) filled within the THA perioperative period and the incidence of new, persistent opioid use. Multivariable logistic regression models were used to evaluate associations between robotic-assisted THA and new, persistent opioid use, adjusting for age, sex, insurance plan, region, location of surgery, and comorbidities.
RESULTS: In the postoperative period, robotic-assisted THA, compared with conventional THA, was associated with a lower mean total MMEs filled per patient (452.2 vs 517.1; P<.001) and a lower mean MMEs per patient per day (71.53 vs 74.64; P<.001). Patients undergoing robotic-assisted THA had decreased odds of developing new, persistent opioid use compared with patients undergoing conventional THA (adjusted odds ratio, 0.82 [95% CI, 0.74-0.90]).
CONCLUSION: Robotic-assisted THA is associated with lower postoperative opioid use and a decreased odds of developing new, persistent opioid use compared with conventional THA. For the purposes of reducing opioid use, our results support the adoption of robotic-assisted THA. [Orthopedics. 2024;47(5):289-294.].
This is a phase I, randomized, double blind, as well as partially blinded (for Cohort 4), placebo-controlled safety, illness, and infection study of a new experimental human challenge stock of the Norovirus genogroup II, genotype 2 (GII.2) isolate designated Snow Mountain virus (SMV), administered to healthy adults 18-49 years of age. Groups of 11 subjects each will be admitted to the inpatient hospital research unit, challenged with live SMV or placebo by oral administration, and remain in isolation in the unit for at least 4 days following challenge. The study duration is 24 - 36 months. Subjects will be followed post-challenge for safety, reactogenicity, and illness (primary objectives), and secondary or exploratory objectives including infection and immune responses. There will be multiple clinical assessments and collection of blood, emesis, saliva, and stool specimens. The primary objectives are to: 1) evaluate the safety and reactogenicity of the GII.2 Snow Mountain norovirus challenge stock and 2) determine a safe and optimal challenge dose of GII.2 Snow Mountain norovirus to achieve illness in a high proportion (= / \> 75%) of subjects. The secondary objectives are to: 1) determine the rate of infection in study participants after norovirus GII.2 challenge, 2) determine the quantity and duration of virus shedding in stool by RT-qPCR, 3) estimate the median time to cessation of shedding, 4) determine the modified Vesikari score as a measure of gastroenteritis severity, 5) determine GII.2 Snow Mountain norovirus-specific Immunoglobulin titers by ELISA before and after the challenge, 6) determine the effect of pre-existing GII.2 Snow Mountain norovirus-specific immunoglobulin in serum and saliva on the rate of infection, 7) determine total and GII.2 Snow Mountain norovirus-specific IgA- and IgG-Secreting Cells in circulation by ELISpot assay, 8) once the optimal challenge dose is determined in secretor positive subjects: investigate the safety and illness rate using that dose of the GII.2 challenge stock in secretor negative subjects.
The invention relates to a traditional Chinese medicinal preparation for treating thrombocytopenia. The preparation comprises the following raw materials in part by weight: 30 parts of astragalus, 30 parts of white peony, 30 parts of Chinese angelica, 30 parts of Indian Buead, 30 parts of unripe bitter orange, 30 parts of suberect spatholobus stem, 30 parts of cooked rehmannia, 30 parts of bupleurum, 15 parts of aromatic turmeric tuber, 15 parts of large head atractylodes rhizome and 15 parts of Chinese date. The preparation comprises clinically acceptable and orally taken dosage forms, preferably decoction, powder, oral liquid preparation and honeyed pill preparation. The raw materials selected can be used together for promoting blood circulation, removing blood stasis, nourishing Yin, tonifying spleen, clearing heat, moistening dryness, regulating Qi and dissolving purpura. 200 patients are clinically treated, and the effective rate is 98 percent. Through clinical observation, the traditional Chinese medicinal preparation has the advantages of low treatment cost, high treatment effect, and no toxic or side effect.
Participants received 200 mg Tedizolid Phosphate once daily intravenous (I.V.) infusion to oral for 6 days, followed by 4 days of placebo.
Participants will place the e-Nose device in their bathroom to record VOCs from the ambient air after they have a bowel movement. In addition to this, all participants will complete 2 blood draws 3 stool collections, and questionnaires over the course of 4 visits during a 3 week period.
Both trio and population designs are popular study designs for identifying risk genetic variants in genome-wide association studies (GWASs). The trio design, as a family-based design, is robust to confounding due to population structure, whereas the population design is often more powerful due to larger sample sizes. Here, we propose KnockoffHybrid, a knockoff-based statistical method for hybrid analysis of both the trio and population designs. KnockoffHybrid provides a unified framework that brings together the advantages of both designs and produces powerful hybrid analysis while controlling the false discovery rate (FDR) in the presence of linkage disequilibrium and population structure. Furthermore, KnockoffHybrid has the flexibility to leverage different types of summary statistics for hybrid analyses, including expression quantitative trait loci (eQTL) and GWAS summary statistics. We demonstrate in simulations that KnockoffHybrid offers power gains over non-hybrid methods for the trio and population designs with the same number of cases while controlling the FDR with complex correlation among variants and population structure among subjects. In hybrid analyses of three trio cohorts for autism spectrum disorders (ASDs) from the Autism Speaks MSSNG, Autism Sequencing Consortium, and Autism Genome Project with GWAS summary statistics from the iPSYCH project and eQTL summary statistics from the MetaBrain project, KnockoffHybrid outperforms conventional methods by replicating several known risk genes for ASDs and identifying additional associations with variants in other genes, including the PRAME family genes involved in axon guidance and which may act as common targets for human speech/language evolution and related disorders.