anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Users of automated vehicles will engage in other activities and take their eyes off the road, making them prone to motion sickness. To resolve this, the current paper validates models predicting sickness in response to motion and visual conditions. We validate published models of vestibular and visual sensory integration that have been used for predicting motion sickness through sensory conflict. We use naturalistic driving data and laboratory motion (and vection) paradigms, such as sinusoidal translation and rotation at different frequencies, Earth-Vertical Axis Rotation, Off-Vertical Axis Rotation, Centrifugation, Somatogravic Illusion, and Pseudo-Coriolis, to evaluate different models for both motion perception and motion sickness. We investigate the effects of visual motion perception in terms of rotational velocity (visual flow) and verticality. According to our findings, the SVCI model, a 6DOF model based on the Subjective Vertical Conflict (SVC) theory, with visual rotational velocity input is effective at estimating motion sickness. However, it does not correctly replicate motion perception in paradigms such as roll-tilt perception during centrifuge, pitch perception during somatogravic illusion, and pitch perception during pseudo-Coriolis motions. On the other hand, the Multi-Sensory Observer Model (MSOM) accurately models motion perception in all considered paradigms, but does not effectively capture the frequency sensitivity of motion sickness, and the effects of vision on sickness. For both models (SVCI and MSOM), the visual perception of rotational velocity strongly affects sickness and perception. Visual verticality perception does not (yet) contribute to sickness prediction, and contributes to perception prediction only for the somatogravic illusion. In conclusion, the SVCI model with visual rotation velocity feedback is the current preferred option to design vehicle control algorithms for motion sickness reduction, while the MSOM best predicts perception. A unified model that jointly captures perception and motion sickness remains to be developed.
BACKGROUND: Hip fractures in frail patients result in excess mortality not accounted for by age or comorbidities. The mechanisms behind the high risk of mortality remain undetermined but are hypothesized to be related to the inflammatory status of frail patients.
METHODS: In a prospective observational exploratory cohort study of hospitalized frail hip fracture patients, 92 inflammatory markers were tested in pre-operative serum samples and markers were tested against 6-month survival post-hip fracture surgery and incidence of acute kidney injury (AKI). After correcting for multiple testing, adjustments for comorbidities and demographics were performed on the statistically significant markers.
RESULTS: Of the 92 markers tested, circulating levels of fibroblast growth factor 23 (FGF-23) and interleukin-15 receptor alpha (IL15RA), both involved in renal disease, were significantly correlated with 6-month mortality (27.5% overall) after correcting for multiple testing. The incidence of postoperative AKI (25.4%) was strongly associated with 6-month mortality, odds ratio = 10.57; 95% CI [2.76-40.51], and with both markers plus estimated glomerular filtration rate (eGFR)- cystatin C (CYSC) but not eGFR-CRE. The effect of these markers on mortality was significantly mediated by their effect on postoperative AKI.
CONCLUSION: High postoperative mortality in frail hip fracture patients is highly correlated with preoperative biomarkers of renal function in this pilot study. The effect of preoperative circulating levels of FGF-23, IL15RA, and eGFR-CYSC on 6-month mortality is in part mediated by their effect on postoperative AKI. Creatinine-derived preoperative renal function measures were very poorly correlated with postoperative outcomes in this group.
AIMS: Activation of the endocannabinoid system by monoacylglycerol lipase (MAGL) blockade may affect the lower urinary tract function. We investigated the effect of an MAGL inhibitor, MJN110, on neurogenic lower urinary tract dysfunction (LUTD) in the mouse model of spinal cord injury (SCI).
METHODS: Female C57BL/6 mice that underwent spinal cord transection at T8-10 level were divided into three groups consisting of (1) vehicle-treated SCI mice, (2) 5 mg/kg, or (3) 10 mg/kg of MJN110-treated SCI mice. MJN110 and vehicle were administered intraperitoneally for 7 days from 4 weeks after spinal cord transection. We then conducted awake cystometrograms and compared urodynamic parameters between three groups. The expression of cannabinoid (CB) receptors, TRP receptors, and inflammatory cytokines in L6-S1 dorsal root ganglia (DRG) or the bladder mucosa were evaluated and compared among three groups. Changes in the level of serum 2-arachidonoylglycerol (2-AG) and bladder MAGL were also evaluated.
RESULTS: In the cystometrogram, detrusor overactivity (DO) parameters, such as the number of nonvoiding contraction (NVC), a ratio of time to the 1st NVC to intercontraction interval (ICI), and NVC integrals were improved by MJN110 treatment, and some effects were dose dependent. Although MJN110 did not improve voiding efficiency, it decreased bladder capacity, ICI, and residual urine volume compared to vehicle injection. MJN110 treatment groups had lower CB2, TRPV1, TRPA1, and inflammatory cytokines mRNA levels in DRG and bladder mucosa. Serum 2-AG was increased, and bladder MAGL was decreased after MAGL inhibitor treatment.
CONCLUSIONS: MAGL inhibition improved LUTD including attenuation of DO after SCI. Thus, MAGL can be a therapeutic target for neurogenic LUTD after SCI.
PURPOSE: To obtain a therapeutic agent for hepatopathy, having proliferating activities on hepatocytes and restoring effects on hepatopathies and useful for acute hepatitis, chronic hepatitis, cirrhosis, etc. CONSTITUTION: This therapeutic agent for hepatopathy contains amino-alcohols of the formula [R<1> is H or phosphono; R<2> is H or (CH2 )n -OR<1> ; (n) is 2-5] or salts thereof as an active ingredient. Commercially available products can directly be used or the compounds of the formula are chemically synthesized. Otherwise, a low-molecular fraction fractionated from an extract of a mammalian small intestinal epithelial mucosal tissue can be used as the compounds of the formula and monoethanolamine is exemplified. The compounds of the formula alone are used or suitably blended with usually used pharmaceutical ingredients and prepared for a peroral administration agent, a parenteral injection, a suppository, etc. The daily dose is 10-5000mg, preferably 50-2000mg expressed in terms of the compounds of the formula administered in divided 3 to 4 portions.
Disclosed are XBP-1/IRE-1 inhibitors having formula disclosed herein. Methods of making and using these inhibitors for the treatment of cancer, in particular B cell cancers, are also disclosed. Also disclosed is a genetic XBP-1-knockout cancer mouse model. In still further aspects, the disclosed subject matter relates to methods for treating oncological and inflammatory disorders in a patient. For example, disclosed herein are methods whereby an effective amount of a compound or composition disclosed herein is administered to a patient having an oncological disorder, for example B-cell chronic lymphocytic leukemia (CLL), and who is in need of treatment thereof. XBP-1 deficiency causes leukemic cells to acquire phenotypes that are disadvantageous for their survival, such as compromised BCR signaling capability and increased surface expression of S1 P1.
Oralone® may cause local adverse reactions. If irritation develops, Oralone® should be discontinued and appropriate therapy instituted. Allergic contact sensitization with corticosteroids is usually diagnosed by observing failure to heal rather than noting a clinical exacerbation as with most topical products not containing corticosteroids. Such an observation should be corroborated with appropriate diagnostic patch testing.

If concomitant mucosal infections are present or develop, an appropriate antifungal or antibacterial agent should be used. If a favorable response does not occur promptly, use of Oralone® should be discontinued until the infection has been adequately controlled. If significant regeneration or repair of oral tissues has not occurred in seven days, additional investigation into the etiology of the oral lesion is advised.

Systemic absorption of topical corticosteroids has produced reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, manifestations of Cushing's syndrome, hyperglycemia, glucosuria, and other adverse effects known to occur with parenterally-administered steroid preparations; therefore, it may be advisable to periodically evaluate patients on prolonged therapy with corticosteroid-containing dental pastes for evidence of HPA axis suppression (see PRECAUTIONS, Laboratory Tests). If HPA axis suppression is noted, an attempt should be made to withdraw the drug or to reduce the frequency of application. Recovery of HPA axis function is generally prompt and complete upon discontinuation of therapy.
The study will be conducted as a non-blinded stepped wedge cluster randomized controlled trial with two arms: onsite HCV management through telemedicine versus HCV management through usual care, which in most cases will be referral to an offsite liver specialist (Referral). The arm assignment will be at the cluster (clinic) level. After an initial period (6 months) in which all clinics implement the control intervention (usual care), at regular intervals (i.e., the "steps") of 6 months duration each, one group of clinics will be randomized to cross over from the Usual Care arm to the Telemedicine arm. In this way, there will be enough time for implementation and assessment of the intervention within each time period. The process continues until all clinics have crossed over to implement telemedicine, and thus all clinics contribute data to both interventions. In addition, patients will be followed for two years post-treatment cessation to assess for reinfection or relapse of HCV RNA.
Renal Impairment

Dosing must be individualized according to the patient's renal function status. For patients with mild renal impairment (creatinine clearance ≥ 50 mL/min to < 80 mL/min), the recommended initial dose of INVEGA is 3 mg once daily. The dose may then be increased to a maximum of 6 mg once daily based on clinical response and tolerability. For patients with moderate to severe renal impairment (creatinine clearance ≥ 10 mL/min to < 50 mL/min), the recommended initial dose of INVEGA is 1.5 mg once daily, which may be increased to a maximum of 3 mg once daily after clinical reassessment. As INVEGA has not been studied in patients with creatinine clearance below 10 mL/min, use is not recommended in such patients. ®®®[See ] Clinical Pharmacology (12.3)

Hepatic Impairment

For patients with mild to moderate hepatic impairment, (Child-Pugh Classification A and B), no dose adjustment is recommended . INVEGA has not been studied in patients with severe hepatic impairment. [see ] Clinical Pharmacology (12.3)®

Elderly

Because elderly patients may have diminished renal function, dose adjustments may be required according to their renal function status. In general, recommended dosing for elderly patients with normal renal function is the same as for younger adult patients with normal renal function. For patients with moderate to severe renal impairment (creatinine clearance 10 mL/min to < 50 mL/min), the maximum recommended dose of INVEGA is 3 mg once daily . ®[see ] Renal Impairment above
Male infertility is a serious ongoing problem, whose causes have not yet been clearly identified. However, since human exposure to silver nanoparticles (AgNPs) has recently increased due to their beneficial properties, the present study aimed to determine the impact of small-size AgNPs on mouse spermatogonia (GC-1 spg) and spermatocytes [GC-2 spd(ts)] in vitro models as well as the ability of these nanostructures to induce inflammation. The results showed a significant dose- and time-dependent decrease in the metabolic activity in both cell models, which was correlated with an increase in the intracellular ROS level. Moreover, increased activity of caspase-9 and -3, together with enhanced expression of CASP3 and p(S15)-p53 proteins, was detected. Further studies indicated a decrease in ΔΨm after the AgNP-treatment, which proves induction of apoptosis with engagement of an intrinsic pathway. The PARP1 protein expression, the activity and protein expression of antioxidant enzymes, the GSH level, and the increased level of p-ERK1/2 indicate not only the engagement of DNA damage but also the occurrence of oxidative stress. The small-size AgNPs were able to induce inflammation, proved by increased protein expression of NF-κB, p-IκBα, and NLRP3, which indicate damage to spermatogonia and spermatocyte cells. Moreover, the PGC-1α/PPARγ and NRF2/Keap1 pathways were engaged in the observed effect. The spermatogonial cells were characterized by a stronger inflammation-based response to AgNPs, which may be correlated with the TNFα/TRAF2-based pathway. Summarizing, the obtained results prove that AgNPs impair the function of testis-derived cells by inducing the redox imbalance and inflammation process; therefore, these NPs should be carefully implemented in the human environment.
ß-Cell dysfunction and decreased insulin sensitivity are the main pathophysiological defects responsible for the development of hyperglycemia. With continuous presence of insulin resistance, progressive loss of ß-cell function is the crucial defect. Hyperglycemia has deleterious effect on β-cell function, which is partially reversible by adequate glycemic control. In newly diagnosed type 2 diabetic patients with severe hyperglycemia, 2 weeks continuous subcutaneous insulin infusion (CSII) can induce adequate glycemic control with improvement of β-cell function. Nearly half of the patients can maintain euglycemia longer than 12 months by transient CSII. The improvement of β-cell function, especially the restoration of the first-phase insulin response is related to sustained euglycemia in the newly diagnosed type 2 diabetic patients. But it is unclear whether any other interventions (such as oral hypoglycemic agents and multiple daily injections) inducing optimal glycemic control in a short period of time can have the same effect. As a multicenter, open-label, randomized, parallel-group study will be needed to further prove and clarify the findings.
Participants with normal hepatic function will receive single oral dose of pimodivir 600 mg (2\*300 mg tablet) under fasted condition on Day 1. The recruitment in Part B will be started based on assessment by Sponsor upon evaluation of partial data obtained in Part A.
The subscapularis (SSC) provides 50 % of total rotator cuff strength and constitutes the anterior part of force couples of the glenohumeral joint. The advances in shoulder arthroscopy have resulted in improved detection and treatment of subscapularis tendon pathology. The prevalence is between 27 and 30 % in all shoulder arthroscopies and between 49 and 59 % in arthroscopic rotator cuff surgery .

It would be advantageous for the surgeon to be able to diagnose a SSC tear clinically before surgery is performed for rotator cuff tear. Magnetic resonance imaging (MRI) scans of the shoulder have been widely used as a diagnostic tool for predicting the rotator cuff injuries. But preoperative MRI scans do not reliably predict SSC tears, whether conventional MRI or MR arthrography is used. Many clinical tests have been published to evaluate the integrity of SSC. The first of these was the lift-off test by Gerber that was reported to be very reliable in patients with complete SSC tears. The internal rotation lag sign (IRLS) published by Hertel et al. was specific but more sensitive than the lift-off test for assessing the SSC. The belly-press test described by Gerber et al. was modified by other authors who called it the Napoleon sign or the modified belly-press test. Positive belly-press tests were found with upper-third SSC tears. More recently, the bear-hug test was published by Barth et al. and represented the most sensitive test compared with lift-off, belly-press and Napoleon tests. However, Yoon et al. found belly-press test was more sensitive compared with bear-hug test in the most recent study. In our institute, we also performed internal rotation resistance test (IRRT) at 0° abduction and 0° external rotation (IRRT0°, Fig. 1) and IRRT at maximal 90° abduction and maximal external rotation (IRRTM) to investigate the function of SSC. These tests use resisted internal rotation as the shoulder is at different abduction and external rotation degrees.

Although many of these tests are performed, SSC lesions are still underdiagnosed before operation. Because these 6 tests mentioned above have a distinct position and manner, the individual test might imply different severity of SSC lesions. The SSC is stretched out and more extension in the abduction and external rotation position compared with internal rotation position. The purpose of this study is to describe the new clinical test (IRRTM) for evaluating SSC integrity and to compare its diagnostic value with the present SSC tests (the lift-off, belly-press, IRLS and bear-hug tests). The hypothesis was that the IRRTM would be the most sensitive test for detecting tears of the SSC.
The dorsal spinal cord is crucial for the transmission and modulation of multiple somatosensory modalities, such as itch, pain, and touch. Despite being essential for the well-being and survival of an individual, itch and pain, in their chronic forms, have increasingly been recognized as clinical problems. Although considerable progress has been made in our understanding of the neurochemical processing of nociceptive and chemical itch sensations, the neural substrate that is crucial for mechanical itch processing is still unclear. Here, using genetic and functional manipulation, we identified a population of spinal neurons expressing neuromedin U receptor 2 (Nmur2+) as critical elements for mechanical itch. We found that spinal Nmur2+ neurons are predominantly excitatory neurons, and are enriched in the superficial laminae of the dorsal horn. Pharmacogenetic activation of cervical spinal Nmur2+ neurons evoked scratching behavior. Conversely, the ablation of these neurons using a caspase-3-based method decreased von Frey filament-induced scratching behavior without affecting responses to other somatosensory modalities. Similarly, suppressing the excitability of cervical spinal Nmur2+ neurons via the overexpression of functional Kir2.1 potassium channels reduced scratching in response to innocuous mechanical stimuli, but not to pruritogen application. At the lumbar level, pharmacogenetic activation of these neurons evoked licking and lifting behaviors. However, ablating these neurons did not affect the behavior associated with acute pain. Thus, these results revealed the crucial role of spinal Nmur2+ neurons in mechanical itch. Our study provides important insights into the neural basis of mechanical itch, paving the way for developing novel therapies for chronic itch. PERSPECTIVE: Excitatory Nmur2+ neurons in the superficial dorsal spinal cord are essential for mechanical but not chemical itch information processing. These spinal Nmur2+ neurons represent a potential cellular target for future therapeutic interventions against chronic itch. Spinal and supraspinal Nmur2+ neurons may play different roles in pain signal processing.
OBJECTIVES: Patients with malignant wounds suffer from physical and psychological symptom burden. Despite psychological support being required, the impact of malignant wounds on patients' psychological distress is poorly investigated. We evaluated psychological distress associated with malignant wounds for patients at their end of life.
METHODS: This study used the secondary analysis of the results of a large prospective cohort study, which investigated the dying process among patients with advanced cancer in 23 palliative care units in Japan. The primary outcome of this study was the prevalence of moderate to severe psychological symptom burden, evaluated by the Integrated Palliative Care Outcome Scale (IPOS)-feeling at peace scores of 2-4. In addition, the factors affecting psychological symptoms were investigated. The quality of death was also evaluated upon death using the Good Death Scale score.
RESULTS: Out of the total 1896 patients, 156 had malignant wounds (8.2%). Malignant wounds were more common in female and young people. The breast, head, and neck were the most prevalent primary sites. More patients with malignant wounds had IPOS-feeling at peace scores of 2-4 than patients without malignant wounds (41.0% vs. 31.3%, p = 0.024). Furthermore, psychological distress was associated with moderate to severe IPOS-pain and the frequency of dressing changes. The presence of malignant wounds did not affect the quality of death.
SIGNIFICANCE OF RESULTS: This study showed increased psychological distress due to malignant wounds. Patients with malignant wounds require psychological support in addition to the treatment of physical symptoms for maintaining their quality of life.
This group include 20 patients with COPD and intermittent claudication. These patients can receive aerobic exercise (by applying treadmill exercise for 20 min) and inspiratory muscle training (by using The BREATHER device with Light/Medium resistance for 3-5 sets /session), for 4 weeks (3 sessions per week) and pursed lip breathing.
The invention belongs to the field of the ulcer treatment with a traditional Chinese medicine, and especially relates to a traditional Chinese medicinal composition for treating the oral ulcer, wherein the traditional Chinese medicinal composition is prepared from specific components according to a specific ratio. A technical scheme of the invention is that the composition is prepared by taking 200-450 parts by weight of calcined gypsum, 150-400 parts by weight of dahurian angelica root, 50-300 parts by weight of Bletilla striata, 50-200 parts by weight of unprepared licorice and 20-200 parts by weight of borneol and mixing them to form powder. According to technical scheme, the calcined gypsum has the efficacies of dampness astringing, flesh engendering, sore astringing and bleeding stopping; the dahurian angelica root has the efficacies of bleeding stopping, swelling relieving, pain relieving and pus discharging, and dampness eliminating; the unprepared licorice has the efficacies of heat clearing and detoxifying, pain relieving, various medicine modulating, and medicinal toxicity and strength alleviating; and borneol has the efficacies of heat clearing and pain relieving, inflammation resisting, bacterium resisting and corrosion resisting. The dahurian angelica root and the Bletilla striata are paired as a monarch medicine and a minister medicine; the calcined gypsum and borneol are used as assistant medicines; and the unprepared licorice is used as a guide medicine. The medicines are mixed to become the powder which has the efficacies of vital qi strengthening and toxin expelling, and caries dispelling and flesh engendering and provides a good environment for the ulcer cell regeneration. The study on animal pharmacodynamics and the pathology show that the medicinal composition which can effectively treat the oral ulcer has the advantages of administration calmness, and safety and nontoxicity.
The placebo will be given for 9 weeks prior to imaging session 1. A rescue drug, Gabapentin, will be provided for pain control. Patients will taper off the Gabapentin 2 weeks before each scan date. After a taper and washout, the drug lamotrigine (cross over) will be administered. At the end of the trial (after imaging session 2), a taper for drug will be given. Patients will be required to maintain a pain diary during the study, documenting the perceived effects of the drug on the severity of their pain and keeping track of their subjective pain ratings day to day. Patients will also complete the McGill Pain Questionnaire at each visit.