anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
FIELD: organic chemistry, biochemistry, pharmacy. SUBSTANCE: invention describes novel compounds of the general formula (I)   where R 1  means acyl radical taken among lower alkoxy-lower alkanoyl (including lower alkoxycarbonyl) where radical of lower alkoxy-group is unsubstituted or substituted with one or more radicals taken independently each of other among halogen atom, lower alkoxy- or pyrrolidinyl-group that is unsubstituted or substituted with one or more radicals taken independently each of other among oxo- or hydroxyl-group; lower alkanoyl that is unsubstituted or substituted with piperidinyl, pyrrolidinyl, tetrahydropyranyl, tetrahydrofuranyl, thiazoli- -dinyl, thiazolyl, indolyl, 4H-1-benzopyranyl, piperidinyl- -oxy-, tetrahydropyranyloxy- or tetrahydrofuryloxy-group that in each case are unsubstituted or substituted with one or more substituents taken independently each of other among oxo-, hydroxyl-, amino-group, lower alkyl and lower alkoxycarbonyl; phenyl-lower alkoxycarbonyl; arylcarbonyl that is substituted with heterocyclyl or morpholine-lower alkyl; phenyl-lower alkanoyl that is substituted with hydroxyl, lower alkyl; and arylsulfonyl; residue that is bound by carbonyl group of amino acid valine and N-acylated by amino-group with lower alkoxy- -carbonyl; R 2  means cyclohexyl or phenyl that are unsubstituted or substituted with one or more radical taken independently each of other among hydroxyl, lower alkoxy-, phenyl-lower alkoxy-, pyridyl-lower alkoxy-group where pyridyl is bound by carbon atom in ring and lower alkoxy-lower alkoxy- -group; R 3  means cyclohexyl, cyclohexenyl, phenyl, naphthyl or tetrahydronaphthyl that are unsubstituted or substituted with one or more radicals taken independently each of other among phenyl, cyanophenyl, phenyl-lower alkyl, halogen atom, cyano-, hydroxyl-, lower alkoxy-, phenyl-lower alkoxy-, pyridyl-lower alkoxy-group where pyridyl is bound by carbon atom in ring, lower alkoxy-lower alkoxy-, alkylenedioxy-group and phenyl- -lower alkanesulfonyl that is unsubstituted or substituted in phenyl radical with one or more radicals taken independently each of other among halogen atom; R 4  means lower alkyl, cyclohexyl or phenyl; R 5  means lower alkyl; n = 1 or 2 or its salts under condition that at least salt-forming group presents. New compounds of the formula (I) show antiviral activity, they exhibit good pharmacokinetics, biological availability and/or good tolerance. Invention describes method of synthesis of compounds of the formula (I), pharmaceutical preparation and composition also. EFFECT: new compounds, improved method of synthesis, valuable medicinal properties. 12 cl, 5 tbl
Participants will receive a single oral Dose 1 of milvexian as DC whole tablets under fasting conditions (Treatment X) in Treatment Period 1 followed by a single oral Dose 1 of milvexian as DC tablets dispersed in water and then mixed with apple sauce under fasting conditions (Treatment Y) in Treatment Period 2 and then a single oral Dose 1 of milvexian as DC tablets dispersed in water administered through a nasogastric (NG) tube under fasting conditions (Treatment Z) in Treatment Period 3 on Day 1 of each Treatment Period during Part 5. There will be a wash-out period of 5 days between Day 1 of adjacent treatment periods.
All patients will receive 4 doses of obinutuzumab on days -14, -10, -6 and -2. Patients without CNS involvement will receive one dose of Liposomal cytarabine for CNS prophylaxis on day -13. Dexamethasone will be given for 5 days with each Liposomal cytarabine dose starting one day prior to the Liposomal cytarabine. Dexamethasone 0.15 mg/kg/dose (max 4mg) IV BID will be given days -14 to -10. Following completion of the Prephase (or at the first sign of progressive disease), all patients will proceed to cycle 1 of O-ICE. O-ICE chemotherapy is given in 21-day (3-week) cycles. Three weekly doses of obinutuzumab will be given days -2 (during the prephase), +6 and +13. Patients will receive ICE chemotherapy (ifosfamide-carboplatin-etoposide) administered on Days 0-2 of Cycle 1.
BACKGROUND: Cerebral ischemia-reperfusion (I/R) injury often leads to neuronal death through persistent neuroinflammatory responses. Recent research has unveiled a unique inflammatory programmed cell death mode known as PANoptosis. However, direct evidence for PANoptosis in ischemic stroke-induced neuronal death has not been established. Although it is widely thought that modulating the balance of microglial phenotypic polarization in cerebral I/R could mitigate neuroinflammation-mediated neuronal death, it remains unknown whether microglial polarization influences PANoptotic neuronal death triggered by cerebral I/R. Our prior study demonstrated that curcumin (CUR) preconditioning could boost the neuroprotective properties of olfactory mucosa-derived mesenchymal stem cells (OM-MSCs) in intracerebral hemorrhage. Yet, the potential neuroprotective capacity of curcumin-pretreated OM-MSCs (CUR-OM-MSCs) on reducing PANoptotic neuronal death during cerebral I/R injury through modulating microglial polarization is uncertain.
METHODS: To mimic cerebral I/R injury, We established in vivo models of reversible middle cerebral artery occlusion (MCAO) in C57BL/6 mice and in vitro models of oxygen-glucose deprivation/reoxygenation (OGD/R) in HT22 neurons and BV2 microglia.
RESULTS: Our findings indicated that cerebral I/R injury caused PANoptotic neuronal death and triggered microglia to adopt an M1 (pro-inflammatory) phenotype both in vivo and in vitro. Curcumin pretreatment enhanced the proliferation and anti-inflammatory capacity of OM-MSCs. The CUR-OM-MSCs group experienced a more pronounced reduction in PANoptotic neuronal death and a better recovery of neurological function than the OM-MSCs group. Bioinformatic analysis revealed that microRNA-423-5p (miRNA-423-5p) expression was obviously upregulated in CUR-OM-MSCs compared to OM-MSCs. CUR-OM-MSCs treatment induced the switch to an M2 (anti-inflammatory) phenotype in microglia by releasing miRNA-423-5p, which targeted nucleotide-binding oligomerization domain 2 (NOD2), an upstream regulator of NF-kappaB (NF-κB) and Mitogen-Activated Protein Kinase (MAPK) signaling pathways, to attenuate PANoptotic neuronal death resulting from cerebral I/R.
CONCLUSION: This results provide the first demonstration of the existence of PANoptotic neuronal death in cerebral I/R conditions. Curcumin preconditioning enhanced the ameliorating effect of OM-MSCs on neuroinflammation mediated by microglia polarization via upregulating the abundance of miRNA-423-5p. This intervention effectively alleviates PANoptotic neuronal death resulting from cerebral I/R. The combination of curcumin with OM-MSCs holds promise as a potentially efficacious treatment for cerebral ischemic stroke in the future.
The invention discloses a traditional Chinese medicine-based medicinal liquor, wherein a traditional Chinese medicine composition comprises the following components in percentage by weight: 35-45% of barbary wolfberry fruit, 35-45% of chili, 1-3% of pseudo-ginseng, 1-3% of safflower, 1-10% of ganoderma lucidum, 1-10% of semen cassia and 1-10% of chrysanthemum. The traditional Chinese medicine-based medicinal liquor has an excellent curative effect in treating dermatophytosis because the Chinese herbs such as barbary wolfberry fruit, chili, pseudo-ginseng, safflower, ganoderma lucidum, semen cassia and chrysanthemum are combined with one another. The traditional Chinese medicine-based medicinal liquor further has the effects of treating ozostomia, dental ulcer and rhinitis, tightening skin, resisting wrinkles, removing blace, whitening spots, and the like. The traditional Chinese medicine-based medicinal liquor also has a remarkable curative effect in treating early-stage cataract and glaucoma. Besides, the traditional Chinese medicine-based medicinal liquor further can be used for expelling parasite and sterilizing. The preparation method of the traditional Chinese medicine composition is simple, convenient to operate and advantageous for popularization.
It is intended to provide an anti-PCI antibody having a function of neutralizing protein C inhibitor (PCI) and utilization thereof. By producing and screening an anti-PCI antibody, an anti-PCI antibody inhibiting the functions of PCI of inhibiting the formation and activity of activated protein C (aPC) is successfully isolated. This antibody regulates the functions of PCI of inhibiting the formation of aPC and/or inactivating aPC, which makes it usable in maintaining the activity of aPC and sustaining the effects of the physiological activities of aPC of preventing the blood coagulation system from activation or an antiinflammatory function. It is also intended to provide utilization of the above antibody in treating thrombosis, sepsis, and so on using aPC. In a treatment with the administration of aPC, the administration of the above antibody contributes to the sustainment of the therapeutic effects. This antibody is usable in treating and preventing thrombosis, sepsis and so on.
Septic shock is a major public health problem. Even if mortality is decreasing, it's still high. Sepsis is a heterogeneous syndrome that encompasses a gamut of immune responses occurring during the host's response to a serious, life-threatening infection. The immune phenotype in sepsis ranges from proinflammatory (systemic inflammatory response syndrome and cytokine storm syndrome) to anti-inflammatory (immune depressed state). In order to apprehend septic shock as a whole, investigators should made a whole immune mapping in each patient. Within immune mapping of septic shock patients, innate lymphoid cells (ILCs) have never been explored.

ILCs include natural killer (NK) cells and three other main subsets, ILC1, ILC2 and ILC3, referred as to 'helper-like ILCs'. Since their discovery, ILCs have been shown to contribute to wound healing and defense against infection, and studies have revealed critical aspects of their differentiation. They are studied by flow cytometry and much of the role of ILCs remains to be elucidated, especially in humans. Like T Helper cells, investigators think it could exist an imbalance of ILCs in the late course of septic shock which could participate to the immune depressed state and the increase of patients' mortality at this stage.

So, investigators want to realize a whole immune mapping in patients managed for a septic shock focusing particularly on the innate lymphoid cells. investigators think that ILC1s and ILC3s could be increased in the patients' blood in the early course of the disease and could participate to the cytokine storm syndrome. On the contrary, ILC2s could be increased in the late stage of the septic shock, in correlation with the immune suppressed state. investigators will compare the blood rates of ILCs in septic shock with the blood rates of ILCs in patients with a bacterial sepsis but without severity criteria.

investigators will include 30 patients in septic shock (group 1) in the medical intensive care unit of the Timone Hospital (RUM - Pr Gainnier) and 30 patients with a bacterial sepsis alone, during a 6 months period. investigatorswill take two kits of blood samples for the group 1, one during the early stage of the septic shock (48 first hours of care) and one during the late stage of the disease (between the fourth and the sixth day). investigators'll take only one kit of blood samples for the group 2. One kit includes one EDTA tube (5 mL) and five Lithium Heparin tubes (25 mL). The immune mapping will be made by Julien Carvelli, a gold medalist resident, in the framework of a Master 2. The analyses will be made in the laboratory of immunology in the Conception Hospital (Pr Vivier's team).
PROBLEM TO BE SOLVED: To prepare a composition, effective is antibacterial, antimold or antiviral uses, especially against Gram-positive bacteria and excellent in safety by combining a specific α-hydroxycarboxylic acid with squalene. SOLUTION: This composition contains a combination of an α- hydroxycarboxylic acid of formula I (R' and R" are each H, an alkyl or phenyl or R' and R" together form a cycloalkyl), its physiologically permissible salt, ethyl ester or methyl ester with squalene. For example, compounds of formula II [(n) is 7-31] and formula III are cited as the compound of formula I. The content of the α-hydroxycarboxylic acid is about 20-30wt.% based on the whole composition. The combination of the compound of formula I with the squalene is blended in an amount of preferably about 0.005-50.0wt.%, especially preferably about 0.01-20.0wt.% based on the whole composition. The composition is capable of suppressing especially the proliferation of Pityrosporum ovale and can be used for preventing the formation of dandruff and treating common acne, etc.
Because fluoxetine is excreted in human milk, nursing while on fluoxetine is not recommended. In one breast-milk sample, the concentration of fluoxetine plus norfluoxetine was 70.4 ng/mL. The concentration in the mother’s plasma was 295.0 ng/mL. No adverse effects on the infant were reported. In another case, an infant nursed by a mother on fluoxetine developed crying, sleep disturbance, vomiting, and watery stools. The infant’s plasma drug levels were 340 ng/mL of fluoxetine and 208 ng/mL of norfluoxetine on the second day of feeding.
Quazepam Tablets may cause confusion and over-sedation in the elderly. Elderly patients generally should be started on a low dose of Quazepam Tablets and observed closely. Elderly and debilitated patients may be more sensitive to benzodiazepines, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. A double-blind controlled sleep laboratory study (N=30) compared the effects of Quazepam Tablets 7.5 mg and 15 mg to that of placebo over a period of 7 days. Both the 7.5 mg and 15 mg doses appeared to be well tolerated. Caution must be used in interpreting this data due to the small size of the study.
Patients receive standard of care consisting of docetaxel IV over 30-60 minutes on day 1; gemcitabine IV over 30 minutes on days 1 and 8; pemetrexed IV over 10 minutes on day 1; or ramucirumab IV over 30-60 minutes and docetaxel IV over 30-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
During the first week of treatment patients in both arms receive prednisone at 1 mg/kg/d. In arm B patients subsequently receive six 21-day courses of pulsed dexamethasone (0.6 mg/kg/d, days 1-4).
Gastrointestinal tumor has a high incidence rate and mortality, which is one of the major diseases that seriously endanger the health of Chinese residents. Postoperative recurrence of colorectal cancer is the main cause of death in patients with advanced colorectal cancer. It is reported that the local recurrence rate after radical resection of colorectal cancer is 1% - 17%, and the 5-year survival rate after reoperation for recurrent and metastatic colorectal cancer is only 5% - 30%. In addition, the 5-year survival rate of locally advanced gastric cancer after operation is only 30-40%.

The adjuvant treatment of locally advanced colorectal cancer and gastric cancer is still mainly radiotherapy and chemotherapy, and the research of anti-vascular targeted therapy combined with adjuvant chemotherapy for locally advanced colorectal cancer and gastric cancer is still under exploration. The research of antiangiogenic drugs combined with adjuvant chemotherapy in the treatment of locally advanced colorectal cancer and gastric cancer can fill this gap. Therefore, this study was designed to explore the efficacy and safety of antiangiogenic drugs combined with adjuvant chemotherapy in the treatment of locally advanced colorectal cancer and gastric cancer.
The study is a phase IIIb, multicenter, single-arm, open-label study designed to evaluate the clinical effectiveness in a real-world setting of olaparib monotherapy in patients with confirmed germline or somatic breast cancer susceptibility gene (gBRCA1/2 or sBRCA1/2) mutations. This study will generate additional data to support other olaparib studies, which may help inform and guide clinical practice. Physician defined the progression-free survival (PFS) for gBRCAm patients is the primary outcome measure. Based on the prevalence of gBRCA1/2 mutations, it is estimated that up to 1400 patients may require screening in order to identify 250 gBRCA mutated patients and 20 sBRCA mutated patients. Patients will be administered two olaparib 150mg tablets in morning and evening of every day after a light meal. Dose reductions may be required for olaparib treatment related toxicities. Patients should continue to receive study treatment until documented physician-defined disease progression as assessed by the investigator (gBRCA mutated patients), RECIST1.1 disease progression (sBRCA mutated patients) or unacceptable toxicity, or for as long as they do not meet any other discontinuation criteria. A positive benefit/risk profile is expected and no ethical issues are identified from exposing patients to olaparib within the planned clinical study.
PURPOSE:To obtain a medical image display system for promoting the division of a medical examination work by providing a shadow reading display means which can display medical image information at every kind of an image generating device, based on its incidental information. CONSTITUTION:Image information generated by each image generating device 2 is transferred and stored to a filing device 4 at every requesting department through a network 3, and various indexes are generated by a filing device 4 and a file manager 8. Subsequently, for instance, in the case wherein a shadow reading doctor being in charge of a CT image executes shadow reading, a shadow reading doctor ID 'A' is inputted by operating a shadow reading display device 7. The shadow reading display device 7 sends this inputted shadow reading ID information 'A' to the file manager 8. The CPU 8b of the file manager 8 retrieves a memory 8a, and knows a fact that its shadow reading doctor is in charge of a CT image, from its sent shadow reading doctor ID information 'A'. Also, the CPU 8b detects the examination ID of a CT image and its patient ID taken charge of by its shadow reading doctor, from an index whose shadow reading is not executed yet.
The invention discloses preparation and application of a pH glucose dual sensitive hydrogel. The hydrogel is formed by crosslinking of phenylboronic acid modified chitosan and an active functional group equipped crosslinking agent through imine bond and phenylboronic acid ester two dynamic covalent bonds, and has injectability and self-repairing performance. The imine bond is stable under normal physiological pH value, can hydrolyze under slightly acidic pH value, and is sensitive to the pH value change. Phenylboronic acid ester can undergo competing reaction in the presence of glucose, so that hydrogel can have network structure change so as to have glucose responsiveness. By regulating the structure, composition and functional groups of phenylboronic acid modified chitosan and the crosslinking agent, the rheological properties of the hydrogel can be adjusted, and activity release of the hydrogel to a substrate can be controlled. The system can be used as a drug carrier to convey various antitumor and diabetes drugs, also can be applied as a tissue engineering scaffold material to cell encapsulation and culture, thus realizing synergic treatment on the drug and cell level.
Increases in Blood Pressure in Adults

MYRBETRIQ/MYRBETRIQ Granules can increase blood pressure. Periodic blood pressure determinations are recommended, especially in hypertensive patients. MYRBETRIQ/MYRBETRIQ Granules is not recommended for use in patients with severe uncontrolled hypertension (defined as systolic blood pressure greater than or equal to 180 mm Hg and/or diastolic blood pressure greater than or equal to 110 mm Hg) [see Clinical Pharmacology (12.2)].

In two, randomized, placebo-controlled, healthy adult volunteer studies, MYRBETRIQ was associated with dose-related increases in supine blood pressure. In these studies, at the maximum recommended dose of 50 mg, the mean maximum increase in systolic/diastolic blood pressure was approximately 3.5/1.5 mm Hg greater than placebo.

In contrast, in adult OAB patients in clinical trials, MYRBETRIQ, taken as monotherapy or in combination with solifenacin succinate 5 mg, the mean increase in systolic and diastolic blood pressure at the maximum recommended mirabegron dose of 50 mg was approximately 0.5 to 1 mm Hg greater than placebo. Worsening of pre-existing hypertension was reported infrequently in patients taking MYRBETRIQ.

Increases in Blood Pressure in Pediatric Patients 3 Years and Older

MYRBETRIQ/MYRBETRIQ Granules can increase blood pressure in pediatric patients. Blood pressure increases may be larger in children (3 to less than 12 years of age) than in adolescents (12 to less than 18 years of age). Periodic blood pressure determinations are recommended. MYRBETRIQ/MYRBETRIQ Granules is not recommended for use in pediatric patients with severe uncontrolled hypertension, defined as a systolic and/or diastolic blood pressure above the 99th percentile plus 5 mm Hg for age, sex, and stature using appropriate reference values [see Adverse Reactions (6.1)].
In Nepal, health facilities need to be strengthened and the staff should be tailored training at health facilities who are designated as birthing center. Although, the health facility readiness survey has shown that health facilities had availability of bag and mask (neonatal) neonatal resuscitation equipment in delivery room (Kc et al., 2020). However, health workers were found to have lack of adequate knowledge on basic emergency and neonatal care (BEmONC) signal function including poor knowledge and skill on newborn resuscitation. resulting in poor child health outcomes during facility-births and had poor knowledge and skill on newborn resuscitation (Lama et al., 2020). Newborn resuscitation simulation training was effective in improving clinical performance of health service providers and perinatal outcomes (Vadla, Moshiro, et al., 2022). NeoNatalie™ is a low-cost, highly portable, and realistic manikin that helps health workers learn and practice standard newborn care and resuscitation measures to better handle birth asphyxia(Laerdal helping save lives, 2022). Use of NeoNatalie, a newborn simulator for neonatal resuscitation training has improved performance of midwives and their motivation(Vadla, Mdoe, et al., 2022). There has been intervention that provided training on helping baby breathe (HBB) in large hospitals in Nepal. However, the use of simulator and training to the midwives at birthing center has not been evaluated for the effectiveness of simulator in increasing their performance and newborn health outcomes. Therefore, this study aimed to improve the performance of skilled-birth attendant in providing resuscitation to the newborn with birth asphyxia by applying simulator-based training.