anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
FIELD: chemistry. ^ SUBSTANCE: invention relates to compounds of formula (1), their tautomers and pharmaceutically acceptable salts. The disclosed compounds have thromobopoietin receptor agonist properties. In formula (1) , A is a nitrogen atom or CH, when A is a nitrogen atom, B is NR9 (where R9 is a C1-10 alkyl group), and when A is CH, B is a sulphur atom, R1 is a phenyl group (the phenyl group is substituted with one or more substitutes selected from a group consisting of halogen atoms, C1-10 alkyl groups and C1-10 alkoxy groups (C1-10 alkyl groups and C1-10 alkoxy groups are unsubstituted or substituted with one or more halogen atoms)), L1 is bond, X is OH, R2 is a C1-10 alkyl group, L2 is a bond, L3 is NH, L4 is a bond or NH, Y is a sulphur atom, and when L4 is a bond, R3 is a piperidinyl group, a piperazinyl group (the piperidinyl group and the piperazinyl group are substituted with substitutes selected from a group containing C1-10 alkoxycarbonyl groups, carboxyl group, hydroxyl groups, di-C1-10 alkylaminocarbonyl groups, C1-10 alkylaminocarbonyl groups and C1-10 alkyl groups (C1-10 alkylaminocarbonyl groups and C1-10 alkyl groups are substituted with a substitute selected from a group containing pyridyl groups, hydroxyl groups and carboxyl groups)), or when L4 is NH, R3 is a C1-10 alkyl group (C1-10 alkyl group is substituted with a substitute selected from a group containing C1-10 alkoxy groups, C1-10 alkoxycarbonyl groups or carboxyl groups). ^ EFFECT: obtaining a thrombopoietin receptor activator which is a formula (1) compound and a medicinal agent which contains the disclosed compound as an active ingredient. ^ 10 cl, 3 tbl, 47 ex
The invention discloses a vitamin A powder and a preparation method thereof, wherein the preparation method comprises the step of embedding vitamin A oil into microcapsules by micro-encapsulation technology; and wall materials used for embedding the vitamin A oil are maltodextrin and Arabic gum. A spray drying method is used in micro-encapsulation. Emulsifier used in spray drying method is compound of glice and sucrose ester. The mass ratio of maltodextrin, sucrose and Arabic gum is 1:(0.15 to 0.25):(0.2 to 0.25). The mass ratio of glice to sucrose ester is 1:(0.05 to 0.07). The mass ratio of Arabic gum to sucrose ester is 1:(0.2 to 0.3). The mass ratio of Arabic gum to vitamin A oil is (0.4 to 0.5):1. Vitamin A powder prepared by the method has high micro-encapsulation efficiency being higher than 96 percent and good water solubility, and can quickly disperse in cold water, and form steady emulsion fluid without mixing.
Tables 7 and 10 enumerate the incidence, rounded to the nearest percent, of treatment-emergent adverse events that occurred during acute therapy of major depressive disorder (up to 12 weeks; dose range of 75 to 225 mg/day), and of panic disorder (up to 12 weeks; dose range of 37.5 to 225 mg/day), respectively, in 2% or more of patients treated with venlafaxine hydrochloride extended-release capsules where the incidence in patients treated with venlafaxine hydrochloride extended-release capsules was greater than the incidence for the respective placebo-treated patients. The table shows the percentage of patients in each group who had at least one episode of an event at some time during their treatment. Reported adverse events were classified using a standard COSTART-based Dictionary terminology. 

The prescriber should be aware that these figures cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the side effect incidence rate in the population studied.
Obstructive sleep apnea (OSA) is a common disorder characterized by intermittent narrowing or closure of the upper airway during sleep. Loss of muscle tone with sleep onset and decreases in ventilatory drive following the loss of the wakefulness stimuli to breathe combine to result in upper airway closure in patients with structurally susceptible upper airways. We hypothesize that training of upper airway muscles will improve sleep apnea by augmenting the resting upper airway muscle tone and ability of the muscles to respond to negative intraluminal pressure. Training with a primitive wind instrument (such as a Digeridoo) and oral pharyngeal exercises (OPE) used in speech therapy have been shown to improve sleep apnea. Individuals who play certain types of wind instruments appear to have a lower risk of sleep apnea. However, to date the mechanism of improvement and the optimal method of upper airway training have not been well defined. We recently completed a study with a facial exerciser (Facial Flex) designed to improve facial muscle tone and found a decrease in snoring in a group with loud snoring but minimal sleep apnea. A group of UF physiologists (including co investigators Drs. Davenport and Silverman) have also demonstrated that brief periods of training with high inspiratory and/or expiratory threshold loads improved cough and swallowing in patients with impairment in upper airway function. Although respiratory pump muscles provide the driving force for pressure generation during training with pressure threshold loads, the upper airway muscle must maintain a patent upper airway resisting high negative or positive intraluminal pressures. For example, the palate must maintain a seal preventing air escape through the nose when high positive pressure is generated through a mouthpiece. Of interest a limited number of very high intensity efforts appears to be the optimal way to train muscles.

We propose targeting a group of mild to moderate OSA patients (apnea-hypopnea index \< 30/hour) who are not severely obese (BMI \< 35 Kg/M2) and do not have significant structural abnormalities of the upper airway or muscle dysfunction. We will perform a randomized controlled trial (training versus sham training) with 25 subjects in each treatment arm using two months of daily training (5 out of 7 days each week). A home sleep study (including EEG) will be performed before and following the training. The change in the apnea-hypopnea index adjusted for sleep stage and body position will be compared. Use of home sleep studies will dramatically reduce the cost of the study. A sleep technologist will educate subjects on performance of maneuvers and meet with them weekly to observe the subject's technique. A training log will be kept by the subjects using training schedule sheets and daily training will be monitored through weekly web-based communication with a study clinician.
The Alpha-Stim® AID CES sham device is identical in appearance to the active device but is inactive and does not emit electrical current to the brain via ear clip electrodes. The sham intervention is one daily 60 minutes Alpha-Stim® CES treatment using ear clip electrodes for 6 weeks.
Methods for preconditioning and/or providing neuroprotection to the animal central nervous system against the effects of cerebral hemorrhage and subarachnoid hemorrhage. Therapeutic agents are administered to the upper third of the nasal cavity to bypass the blood-brain barrier and access the central nervous system directly to avoid unwanted and potentially lethal side effects. Therapeutic agents include those substances that interact with iron and/or copper such as iron chelators, copper chelators, and antioxidants. A particular example of such therapeutic agents is the iron chelator deferoxamine (DFO). An effective amount of DFO may be administered to the upper third of the nasal cavity of a patient at risk for, or diagnosed with, cerebral hemorrhage and subarachnoid hemorrhage. The effective amount of DFO is delivered directly to the patient's central nervous system for preconditioning, preventing and/or treating the cerebral hemorrhage and subarachnoid hemorrhage.
Four days of SREC/Usual cigarette/product use as regular with daily diary. Admitted to hospital research ward on Day 5 and 6 for 2 hospital day visits that includes a standardized session of product use; 4-hr abstinence; PK blood draws; ad libitum use of product; CV monitoring, 12-hr urine collections, and 12-hr circadian blood draws.
Risk Summary

There are no data on the presence of tigecycline in human milk; however, tetracycline-class antibacterial drugs are present in breast milk. It is not known whether tigecycline has an effect on the breastfed infant or on milk production. Tigecycline has low oral bioavailability; therefore, infant exposure is expected to be low. Tigecycline is present in rat milk with little or no systemic exposure to tigecycline in nursing pups as a result of exposure via maternal milk. When a drug is present in animal milk, it is likely that the drug will be present in human milk. 

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for tigecycline for injection and any potential adverse effects on the breastfed child from tigecycline for injection or from the underlying maternal condition (see Clinical Considerations). 

###  Clinical Considerations

Because of the theoretical risk of dental discoloration and inhibition of bone growth, avoid breastfeeding if taking tigecycline for injection for longer than three weeks. A lactating woman may also consider interrupting breastfeeding and pumping and discarding breastmilk during administration of tigecycline for injection and for 9 days (approximately 5 half-lives) after the last dose in order to minimize drug exposure to a breastfed infant.
Asthma prevalence has steadily increased in the United States since the early 1980s; currently, more than 20 million people are diagnosed with asthma. Individuals with this disease may experience periodic attacks of wheezing, shortness of breath, chest tightness, and coughing. While there are many known causes of asthma, including tobacco smoke and other allergens, the exact cause of some asthma cases remains unknown. Research has shown that in some individuals, respiratory airway infections may play a role in the onset and severity of the disease. Inhaled corticosteroids are commonly used to treat asthma; however, they do not effectively control symptoms for everyone. Clarithromycin, an antibiotic medication used to treat bacterial infections, may be an effective asthma treatment for individuals who do not respond well to inhaled corticosteroids. The purpose of this study is to evaluate the effectiveness of clarithromycin at reducing asthma symptoms.

This study will begin with a 4-week run-in period to standardize participants' asthma medication usage. During this time, all participants will stop their current asthma medications and instead will receive inhaled fluticasone twice a day. Albuterol will be available as a rescue medication if necessary. Study visits will take place every 2 weeks. Blood and saliva samples will be obtained for laboratory tests and participants will complete standardized questionnaires to assess asthma symptoms and quality of life. Spirometry will be performed to measure lung function. Medication adherence will be monitored with a daily diary and an electronic pill counting device. At the end of Week 4, participants will be evaluated for study eligibility. If eligible, participants will undergo a bronchoscopy and a lung biopsy to test for Mycoplasma pneumoniae and Chlamydia pneumoniae, two bacteria that have been identified as possible factors in the development of asthma.

The treatment phase of the study will last 16 weeks. Participants will be randomly assigned to receive either 500 mg of clarithromycin or placebo twice a day, plus inhaled fluticasone. At monthly study visits, spirometry and blood collection will be performed. Standardized questionnaires to assess asthma symptoms will be completed every 2 weeks. Medical adherence will continue to be monitored. At the end of Week 16, participants will stop receiving clarithromycin or placebo, but will continue to receive fluticasone. Asthma symptoms, rescue medication usage, quality of life, and lung capacity will be assessed; tissue samples will be examined for the presence of Mycoplasma pneumoniae and Chlamydia pneumoniae. An 8-week washout period will follow to observe any lingering medication effects and to monitor for safety. Monthly study visits during this period will include spirometry and blood collection.
Ocular levels of IL-1β, TNFα, IL-8, and IL-6 correlate with progression of diabetic retinopathy (DR). Müller cells (MC), which are crucial to maintaining retinal homeostasis, are targets and sources of these cytokines. We explored the relative capacities of these four DR-associated cytokines to amplify inflammatory signal expression both in and between human MC (hMC) and retinal microvascular endothelial cells (hRMEC) and in the mouse retina. Of the four cytokines, IL-1β was the most potent stimulus of transcriptomic alterations in hMC and hRMEC in vitro, as well as in the mouse retina after intravitreal injection in vivo. Stimulation with IL-1β significantly induced expression of all four transcripts in hMC and hRMEC. TNFα significantly induced expression of some, but not all, of the four transcripts in each cell, while neither IL-8 nor IL-6 showed significant induction in either cell. Similarly, conditioned media (CM) derived from hMC or hRMEC treated with IL-1β, but not TNFα, upregulated inflammatory cytokine transcripts in the reciprocal cell type. hRMEC responses to hMC-derived CM were dependent on IL-1R activation. In addition, we observed a correlation between cytokine expression changes following direct and CM stimulation and NFκB-p65 nuclear translocation in both hMC and hRMEC. Finally, in mice, intravitreal injections of IL-1β, but not TNFα, induced retinal expression of Il1b and CXCL8 homologues Cxcl1, Cxcl2, Cxcl3, and Cxcl5, encoding pro-angiogenic chemokines. Our results suggest that expression of IL-1β, TNFα, IL-8, and IL-6 may be initiated, propagated, and sustained by autocrine and paracrine signals in hRMEC and hMC through a process involving IL-1β and NFκB. Targeting these signals may help thwart inflammatory amplification, preventing progression to vision-threatening stages and preserving sight.
Participants will receive placebo once daily for 12 weeks in Part 1. Clinical non-responders will receive 45 mg upadacitinib once daily for 12 weeks in Part 2.
Enrolled patients will receive the following treatment: 300 mg/m2 of nab-paclitaxel (Hengrui Pharmaceutical, Lianyungang, China) and 200 mg of PD-1 inhibitor (camrelizumab; Hengrui Pharmaceutical, Lianyungang, China) via a 30-min intravenous infusion on day 1. The treatment was repeated every three weeks.
Phase IIa study, 1:1 randomized, double-blind, placebo-controlled, parallel-design, multi-center study. Each breast cancer patient will be randomly assigned into one of two treatment arms receiving either Myelo001 or placebo as a tablet. Investigational medicinal product is taken as supportive care for 23 consecutive days during chemotherapy treatment. Hematologic and safety parameters as well as actual begin and doses of following chemotherapy cycles will be assessed. A single primary variable will be analyzed with test statistics based on frequent absolute neutrophil measurements. Additionally, in a subgroup of patients biomarkers and pharmacokinetics of Myelo001 will be investigated.
PURPOSE OF REVIEW: Revisions of multiple sclerosis (MS) diagnostic criteria enable clinicians to diagnose patients earlier in the biologic disease course. Prompt initiation of therapy correlates with improved clinical outcomes. This has led to increased attention on the earliest stages of MS, including the MS prodrome and radiologically isolated syndrome (RIS). Here, we review current understanding and approach to patients with preclinical MS.
RECENT FINDINGS: MS disease biology often begins well before the onset of typical MS symptoms, and we are increasingly able to recognize preclinical and prodromal stages of MS. RIS represents the best characterized aspect of preclinical MS, and its diagnostic criteria were recently revised to better capture patients at highest risk of conversion to clinical MS. The first two randomized control trials evaluating disease modifying therapy use in RIS also found that treatment could delay or prevent onset of clinical disease.
SUMMARY: Despite progress in our understanding of the earliest stages of the MS disease course, additional research is needed to systematically identify patients with preclinical MS as well as capture those at risk for developing clinical disease. Recent data suggests that preventive immunomodulatory therapies may be beneficial for high-risk patients with RIS; though management remains controversial.
TPO receptor agonists (TPO-RAs) are a class of clinical second-line regimens for the treatment of primary immune thrombocytopenia (ITP). It can promote megakaryocyte maturation and increase platelet production, but its effect on immunosuppressive cells in patients with ITP has not been explored. Sixty-two ITP patients and 34 healthy controls (HCs) were included in this study. The proportion and functions of myeloid-derived immunosuppressive cells (MDSCs) in ITP patients and HCs were investigated. We found that the proportion and function of MDSCs in ITP patients treated with TPO-RAs were significantly higher than those treated with glucocorticoids (GCs), which was correlated with the clinical efficacy. The proportion and function of cytotoxic Th1 cells and CD8+T cells decreased, while the proportion and immunosuppressive function of Treg cells increased in ITP patients treated with TPO-RAs. We further proved, through MDSC depletion tests, that the inhibitory effect of MDSCs on Th1 cells and the promotion of Treg cells in the original immune micro-environment of GCs-treated ITP patients were impaired; however, these MDSCs' functions were improved in TPO-RAs-treated patients. Finally, we found that the KLF9 gene in MDSCs cells of ITP patients treated with TPO-RAs was down-regulated, which contribute to the higher mRNA expression of GADD34 gene and improved function of MDSCs. These results demonstrate a novel mechanism of TPO-RAs for the treatment of ITP through the assessment of MDSCs and their subsequent impact on T cells, which provides a new basis for TPO-RAs as first-line treatment approach to the treatment of ITP.
Male infertility is a complex issue influenced by multiple environmental and pathological factors. In this context, the impact of Human papillomavirus (HPV) infection on male fertility remains controversial. The introduction of new WHO 2021 evaluation criteria, included in the 6th ed. of Laboratory Manual for the examination and processing of human semen, i.e. DNA fragmentation index (DFI), slow and rapid progressive motility, could provide additional information about this correlation. 121 semen samples of male partners of HPV-positive women attending In Vitro Fertilization (IVF) were evaluated following WHO 2021 and HPV-DNA test. Comparing HPV-negative and positive samples for rapid and slow progressive motility showed significantly different results (p = 0.0018, p = 0.0004), contrary to what was observed for total progressive motility. Regarding sperm DFI, only high-risk HPV infections affected DNA integrity. In addition, the correlation between the different semen parameters revealed a significant correlation between midpiece morphological defects and rapid progressive motility in the HPV-positive group (rho = 0.43, p = 0.0006). In conclusion, WHO 2021 provides additional information regarding HPV's impact on seminal parameters. The correlation between HPV positivity, midpiece defects and a higher rapid progressive motility opens new research perspectives that may help unravel the issues surrounding the role of HPV in compromising sperm quality.
FIELD: medicine, sorbents. SUBSTANCE: method involves immobilization of α 2 -macroglobulin on a solid carrier and the following treatment with a modifying agent of thiolester loop. Immobilized α 2 -macroglobulin is treated additionally with N-acetylneuraminic acid before blockade of nonreacted active carrier groups. Optimal results are obtained in concentration of N- acetylneuraminic acid 0.5-1.2 mg/ml of reagent mixture. EFFECT: decreased anticomplementarity, enhanced sorption activity of product. 2 cl, 2 tbl, 6 ex
The objectives of this study are to build the safety database for simufilam (PTI-125) and to investigate its effects on biomarkers, cognition and neuropsychiatric symptoms during 12-month twice-daily administration in mild-to-moderate AD patients. Additional objectives are to assess differences in cognition and neuropsychiatric symptoms between active and placebo arms in the 6-month randomized period. All subjects will undergo lumbar puncture at screening for baseline testing of cerebrospinal fluid (CSF) total tau and Abeta42, and the first 50 subjects will also provide a CSF sample at Month 6 or Month 12 for evaluation of change from baseline in CSF biomarkers. CSF will not be required of subjects with prior CSF, PET or MRI evidence of Alzheimer's disease. Plasma biomarkers will be evaluated in all subjects. Safety will be assessed by blood tests, electrocardiograms, adverse event monitoring and, at Months 12 and 24, full physical examinations.
Compsns. that control the diurnal/nocturnal rhythms of human beings comprise three mixts., the first reinforces the rhythm and acts as a tonic and stimulant, the second slows the biological rhythm and stimulates the sexual sphere, and the third calms the rhythm. The first mixt. contains an alkaloid, an analeptic, a psycho-active agent, and a vitamin. The second mixt. contains a tranquilliser and an anti-histamine. By controlling the biological rhythms, the compsns. are useful in correcting sexual disorders of psychosomatic origin, such as nervousness, frigidity, and other neurotic symptoms connected with sex.
PURPOSE: To describe the in toto explantation of the CyPass® Micro-Stent and its conceivable complications.
METHODS: This is a case series of eighteen eyes from fourteen patients who underwent CyPass® Micro-Stent implantation due to mild to moderate glaucoma and who subsequently suffered from loss of endothelial cell density. Consequently, the CyPass® Micro-Stent was in toto explanted. The surgical procedure and its complications are described and compared with trimming of the CyPass® Micro-Stent.
RESULTS: A postoperative hyphema was developed in 8 of the 18 eyes. In four of them the hyphema was self-limiting, while in two patients an anterior chamber irrigation was necessary. One patient suffered from a severe intracameral bleeding and iridodialysis during explantation, so that the base of the iris had to be scleral fixated. The remaining explantations were without complications.
CONCLUSION: Dealing with implanted CyPass® Micro-Stents poses a challenge for ophthalmic surgeons. An in toto removal can be traumatic, since the CyPass stent often is fibrotic encapsulated and fused with the surrounding tissue. Alternatively, trimming of the CyPass is also a viable option to avoid further endothelial damage. Reported complications of CyPass trimming are consistent with those that can occur after explantation. Further data on the development of the endothelial cells after trimming or explantation are not yet available. Therefore, it remains open whether trimming of the CyPass, in contrast to complete removal, carries the risk of further endothelial cell loss.