anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Neuronal Tau protein hyperphosphorylation (PPtau) is a hallmark of tauopathic neurodegeneration. However, a reversible brain PPtau occurs in mammals during either natural or "synthetic" torpor (ST), a transient deep hypothermic state that can be pharmacologically induced in rats. Since in both conditions a high sleep pressure builds up during the regaining of euthermia, the aim of this work was to assess the possible role of post-ST sleep in PPtau dephosphorylation. Male rats were studied at the hypothermic nadir of ST, and 3-6 h after the recovery of euthermia, after either normal sleep (NS) or total sleep deprivation (SD). The effects of SD were studied by assessing: (i) deep brain temperature (Tb); (ii) immunofluorescent staining for AT8 (phosphorylated Tau) and Tau-1 (non-phosphorylated Tau), assessed in 19 brain structures; (iii) different phosphorylated forms of Tau and the main cellular factors involved in Tau phospho-regulation, including pro- and anti-apoptotic markers, assessed through western blot in the parietal cortex and hippocampus; (iv) systemic factors which are involved in natural torpor; (v) microglia activation state, by considering morphometric variations. Unexpectedly, the reversibility of PPtau was more efficient in SD than in NS animals, and was concomitant with a higher Tb, higher melatonin plasma levels, and a higher frequency of the microglia resting phenotype. Since the reversibility of ST-induced PPtau was previously shown to be driven by a latent physiological molecular mechanism triggered by deep hypothermia, short-term SD soon after the regaining of euthermia seems to boost the possible neuroprotective effects of this mechanism.
The planned cohorts in part A were axitinib 5mg twice a day plus AK104 10mg/kg every 3 weeks. A minimum of three patients were initially enrolled at the first dose level. If a dose-limiting toxicity occurred, then the cohort would be expanded to a total of six patients. Responses were evaluated by investigators using both RECIST version 1.1 and Immune-Related RECIST (irRECIST).
The EG underwent an additional 30-minute group PNE program, followed by the usual preoperative education program from the hospital. The PNE program used in this TKA study was an adaptation of the PNE program developed for LS. The educational program was designed to be delivered by a physical therapist in a group session to patients prior to their TKA.
Premature Closure of Fetal Ductus Arteriosus

Avoid use of NSAIDs, including LICART, in pregnant women at about 30 weeks gestation and later. NSAIDs, including LICART, increase the risk of premature closure of the fetal ductus arteriosus at approximately this gestational age.

Oligohydramnios/Neonatal Renal Impairment

Use of NSAIDs, including LICART, at about 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation.

Oligohydramnios is often, but not always, reversible with treatment discontinuation. Complications of prolonged oligohydramnios may, for example, include limb contractures and delayed lung maturation. In some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required.

If NSAID treatment is necessary between about 20 weeks and 30 weeks gestation, limit LICART use to the lowest effective dose and shortest duration possible. Consider ultrasound monitoring of amniotic fluid if LICART treatment extends beyond 48 hours. Discontinue LICART if oligohydramnios occurs and follow up according to clinical practice [see Use in Specific Populations (8.1)].
PURPOSE: The aim of this study is to uncover the anti-inflammatory propertity of andrographolide (AGP) in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and the underlying mechanisms related to the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome pathway.
METHODS: An in vivo experiment was conducted on murine model of AECOPD through endotracheal atomization of elastase and lipopolysaccharide (LPS). Intraperitoneal AGP was administered four times. NLRP3 inflammasome pathway molecules were examined using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. By using enzyme-linked immunosorbent assay (ELISA), we tested interleukin (IL)-1β levels in bronchoalveolar lavage fluid. An in vitro study was conducted to determine how AGP impacts the NLRP3 inflammasome in THP-1 derived macrophages. The levels of molecules involved in the pathway were measured. Furthermore, molecular docking analyses were carried out to investigate the interactions between AGP and pathway targets.
RESULTS: In the in vivo study, NLRP3 inflammasome activation was observed in mice experiencing AECOPD. The administration of high-dose AGP demonstrated a mitigating effect on inflammatory cells infiltration in the lungs. Moreover, AGP administration effectively suppressed the expression of NLRP3, apoptosis associated speck-like protein that contains a CARD (PYCARD), cysteinyl aspartate-specific protease-1 (Caspase-1), IL-1β, and IL-18 at both the genetic and protein levels. In the in vitro experiment, IL-1β levels were significantly elevated in THP-1 derived macrophages with activated inflammasome compared to the control group. Furthermore, the downregulation of NLRP3, CASP1, and IL1B genes was observed upon the inhibition of NLRP3 expression through small interfering RNA (siRNA). AGP demonstrated inhibitory effects on the gene expression and protein levels of NLRP3, Caspase-1, and IL-1β. Additionally, molecular docking analysis confirmed that AGP exhibited a favorable binding affinity with all five targets of the pathway.
CONCLUSION: AGP effectively inhibited NLRP3 inflammasome activation and mitigated the inflammatory reaction of AECOPD both in animal models and in vitro experiments, highlighting the potential of AGP as a treatment for AECOPD with anti-inflammatory properties.
Participants in this condition will be asked to respond to one randomly selected self-reflection prompt about physical activity from a library of 28 prompts once a day over 28 days \[4 weeks\]. As with the experimental condition, participants will also complete the same daily survey which includes questions about how many minutes they spent doing light, moderate, and vigorous exercise the day before, in addition to how many hours they spent watching television, using the computer, and sitting. The survey also contains the 24 item Multidimensional Psychological Flexibility Inventory adapted for ecological momentary assessment and questions asking participants to rate the extent to which they are currently feeling 8 emotions, their current motivation to exercise, and their stress the day before. This is estimated to take 10 minutes to complete daily. Participants will have the option to review additional educational content about values clarification and their previous written responses.
BACKGROUND: Delirium is highly prevalent in the Intensive Care Unit (ICU), and managing it in critically ill patients with severe comorbidities is challenging due to transient nature of symptoms. However its significance is underestimated, often overlooked and misdiagnosed by healthcare providers. In Nepal, limited studies has been done on delirium in medical ICUs hence this study aims to assess short-term outcome of admitted patients in delirium.
METHODS: Descriptive cross-sectional observational study was conducted among 92 patients referred from medical ICU with history of disorientation and altered sensorium, assessed during consultation liaison and meeting the criteria for delirium. Data were collected using semi-structured proforma. Richmond Agitation Sedation Scale and Delirium Rating Scale-Revised 98 were used to know the pattern and severity of delirium at day 0 and seven respectively and phone follow-up was done at three months. Data were tabulated and analyzed using SPSS version 25.0.
RESULTS: Hyperactive delirium (57.6%) was most common in medical ICU. Out of total patients, 63.2% improved, 23% became worse and 13.8% remain static with treatment. Mean length of hospital stay was 11.1 days. Hypoactive delirium was associated with longer hospital stay and increased mortality. Significant association was found between length of ICU stay and outcome in terms of mortality and response to treatment.
CONCLUSIONS: Study underscores the prevalence of hyperactive delirium as the predominant pattern in MICU settings. However, it is crucial to highlight the significance of hypoactive delirium due to its poor treatment response and prolonged ICU stays compared to other forms.
Siponimod tablet administered orally once daily. Titration period, Day 1 to Day 6, first dose is either 0.1 mg or 0.25 mg up to daily dose of either 0.5 mg, 1 mg or 2 mg (depending on CYP2C9 genotype and body weight).
Participants will ingest 50 mg of losartan, an angiotensin receptor blocker, by mouth on two consecutive days. The first tablet will be consumed on day 1 at 0700 hrs. The second tablet will be consumed at 1900 hrs and the final tablet will be consumed at 0700hrs on day 2. Participants will undergo a Hyperoxic Hypercapnic Ventilatory Response Test, a Hypoxic Hypercapnic Ventilatory Response Test, and Repeated Hypoxic Apneas before and after a Hypoxic Sleep Study.
Patients in this group will receive written information regarding the recommended levels of exercise (i.e., at least 150 min of moderate-intensity or 75 min of vigorous-intensity aerobic exercise every week) that they can perform at home (self-management) while continuing to receive their standard treatment. They will also be provided with a daily exercise log to record their exercise type, frequency, and intensity.
Pharmaceutical solutions, especially for parenteral administration, consist of stable aqueous solutions containing coenzyme Q and comprising coenzyme Q, especially coenzymes Q4 to Q10, water and sufficient polyoxyethylene-(hydrogenated castor oil) and propylene glycol to solubilize coenzyme Q.  The polyoxyethylene-(hydrogenated castor oil) preferably contains 40 to 50 mol of ethylene oxide per mol of hydrogenated castor oil and less than 5 parts by weight thereof are present per part by weight of coenzyme Q.  Generally 1 to 4 parts by weight of propylene glycol are present per part by weight of coenzyme Q.  The solutions may be prepared by mixing coenzyme Q, polyoxyethylene-(hydrogenated castor oil) and propylene glycol, gradually adding distilled water thereto and then warming on a water bath.  The coenzyme Q may be used in finely powdered form or dissolved in benzyl alcohol. Specification 1112568 is referred to.
Each ESBRIET capsule contains 267 mg of pirfenidone, which belongs to the chemical class of pyridone. ESBRIET is available as a white hard gelatin capsule for oral administration.

The chemical name of pirfenidone is 5-methyl-1-phenyl-2-1(H)-pyridone. It has a molecular formula of C12H11NO and a molecular weight of 185.23. The structural formula of pirfenidone is:

Pirfenidone is a white to pale yellow, non-hygroscopic powder. It is more soluble in methanol, ethyl alcohol, acetone and chloroform than in water and 1.0 N HCl. The melting point is approximately 109°C.

ESBRIET capsule contains pirfenidone and the following inactive ingredients: microcrystalline cellulose, croscarmellose sodium, povidone, and magnesium stearate.

In addition, the capsule shell contains gelatin and titanium dioxide. The capsule brown printing ink includes shellac, iron oxide black, iron oxide red, iron oxide yellow, propylene glycol, ammonium hydroxide.
PROBLEM TO BE SOLVED: To obtain a medicinal composition of human thrombopoietin containing an aqueous composition stably reservable by adding an effective amount of histidine to stabilize a composition of thrombopoietin. SOLUTION: A composition of thrombopoietin is stabilized by adding preferably 10-100 mM of histidine thereto. Preferably, the form of the composition is freeze-dried powder. The composition contains preferably 0.05% concentration of surface adsorption suppressor (e.g. polysolvate 80) selected from the group consisting of human thrombopoietin(TPO), physiologically permissible buffer solution (e.g. sodium phosphate buffer solution), a nonionic surfactant (e.g. polyoxyethylene fatty sorbitate) and a polyol (e.g. polyethylene glycol) and an isotonic amount of physiologically permissible salt. Preferably, the composition is an aqueous solution having pH 5.5-6.5.
The efficacy and safety of levonorgestrel and ethinyl estradiol were studied in 2 one-year clinical trials of subjects age 18 to 49. There were no exclusions for body mass index (BMI), weight, or bleeding history.

The primary efficacy and safety study (313-NA) was a one-year open-label clinical trial that treated 2,134 subjects in North America. Of these subjects 1,213 (56.8%) discontinued prematurely, including 102 (4.8%) discontinued by the Sponsor for early study closure. The mean weight of subjects in this study was 70.38 kg. The efficacy of levonorgestrel and ethinyl estradiol was assessed by the number of pregnancies that occurred after the onset of treatment and within 14 days of the last dose. Among subjects 35 years or less, there were 23 pregnancies (4 of these occurred during the interval 1 to 14 days after the last day of pill use) during 12,572 28-day pill packs of use. The resulting total Pearl Index was 2.38 (95% CI: 1.51, 3.57) and the one-year life table pregnancy rate was 2.39 (95% CI: 1.57, 3.62). Pill pack cycles during which subjects used back-up contraception or were not sexually active were not included in these calculations. Among women 35 years or less who took the pills completely as directed, there were 15 pregnancies (method failures) resulting in a Pearl Index of 1.55 (95% CI: 0.87, 2.56) and the one-year life table pregnancy rate was 1.59 (95% CI: 0.95 to 2.67).

In a second supportive study conducted in Europe (315-EU), 641 subjects were randomized to levonorgestrel and ethinyl estradiol (n=323) or the cyclic comparator of 0.1 mg levonorgestrel and 0.02 mg ethinyl estradiol (n=318). The mean weight of subjects in this study was 63.86 kg. The efficacy analysis among women 35 years or less included 2,756 levonorgestrel and ethinyl estradiol pill packs and 2,886 cyclic comparator pill packs. There was one pregnancy in the levonorgestrel and ethinyl estradiol group that occurred within 14 days following the last dose. There were three pregnancies in the cyclic comparator group.

###  Inhibition of Menses (Bleeding Profile)

The bleeding profile for subjects in Study 313-NA also was assessed. Women with a history of unscheduled bleeding and/or spotting were not excluded from the study.

In those subjects who provided complete bleeding data, the percentage of patients who were amenorrheic in a given cycle and remained amenorrheic through cycle 13 (cumulative amenorrhea rate) was determined (Figure 2).

Figure 2: Percentage of Subjects with Cumulative Amenorrhea for Each Pill Pack through Pill Pack 13

When prescribing levonorgestrel and ethinyl estradiol, the convenience of having no scheduled menstrual bleeding should be weighed against the inconvenience of unscheduled bleeding and spotting (see WARNINGS, 11).
Eyes will be randomized on the day of endolaserless vitrectomy surgery or first postoperative 1-2 week visit to a group (q16week Group) where 2 additional mandatory postoperative q4weeks IAI will be followed by mandatory q16weeks IAI for 52 weeks follow-up. Starting at week 12 in the q16 group, eyes may be eligible to receive additional 2mg IAI (intravitreal aflibercept) (monthly) treatment.
Completion of informed consent and participant screening will be followed by a washout period of minimum 18 hours (wherein participants will be asked to avoid application of cleansers, lotions, or perfumes to both forearms and inner elbows) prior to the first visit (Visit 1) of the study. During Visit 1, study personnel will confirm that the washout period has been successfully completed. Participants will wash their forearms and inner elbows with a standardized soap and dry them using paper towels for each arm. After the participants' forearms and inner elbows have fully dried, study personnel will use a Corneometer® (which measures skin hydration) to record baseline measurements of the skin within 2-inch x 2-inch squares (starting about two inches above the wrist) marked with a non-toxic marker on the volar forearms and inner elbows of the participants. Thereafter, participants will be randomized to the two SBPs, Marathon® or Cavilon™ (designated SBP). The designated SBP will be applied to the volar forearm and inner elbow "test areas" on the participant's dominant arm (as determined by the participant). The other SBP will be applied to the volar forearm and inner elbow "test areas" on the participant's non-dominant arm. A distinct area of each volar forearm will be used as an "untreated control area". Corneometer® measurements will be taken again on the same day after the SBPs have been left to dry for at least one minute or have fully dried. Thereafter, subsequent measurements will be taken daily over a seven-day period with a two-day break over the weekend. Each participant will commence the study on Monday or Tuesday. This will permit daily readings for the first 72 hours, which is the more important window to evaluate SBP wear time. There will be a two-day break in measurements over the weekend, after which Corneometer® measurements will be taken either on Monday, or Monday and Tuesday, depending on the participants' start date. Participants will be allowed to bathe their arms using a standardized soap provided by the study personnel but will be asked to minimize scrubbing and any other abrasion of the volar forearms and inner elbows. In addition, participants will be instructed not to engage in activities, for eg, sports (eg, tennis) or holding a baby that may cause significant abrasion on one arm and not the other. On the last visit of the study (Visit 6), study personnel will take the last set of Corneometer® measurements. In addition, participants will also complete surveys regarding their experience with the SBPs on specific days during study participation.

The Corneometer® measurements will help determine the presence of the SBPs and their deterioration over time. Skin treated with the SBPs will typically have lower readings than untreated skin. As the SBPs break down, the corresponding readings are expected to rise.
The invention is concerned with a kind of pure Chinese materia medica preparation to cure acyesis of ovulation dysfunctional female, belonging to medication technology field. It relates to 10 to 20 g curculigo orchioides,10 to 20 g epimedium,10 to 20 g dodder, 10 to 20 g Chongyuzi, 15 to 20 g tuber fleeceflower,15 to 20 g rhizome of king solomonseal, 15 to 20 g deglued antler powder, 10 to 15 g Zanthoxylum pipertum DC, 10 to 15 g Chinese photinia leaf, 20 to 30 g fluorite, 10 to 20 g morinda root, 10 to 20 g broomrape, 10 to 15 g pangolin scales, 10 to 25 g fruit of beautiful sweetgum, 15 to 25 g seed of cow-fat, 20 to 25 g nutagrass flatsedge rhizome, 15 to 20 g angelica, 10 to 15 g earthworm and 10 to 15 g dried human placemta. Grind those materials and fry for two times, filtrate, unite the filtrate and concentrate into soup for three times a day. This direction promotes ovulating by adjusting pituitary-hypothalamus-gonad (ovary) system. The effect is remarkable and the number of days for taking medicine is few, just lasting 12 days after catamenia. The direction does not have influence to female and gestation fetus without teratogenic action.
BACKGROUND: Diabetic cardiomyopathy (DCM) poses a growing health threat, elevating heart failure risk in diabetic individuals. Understanding DCM is crucial, with fibroblasts and endothelial cells playing pivotal roles in driving myocardial fibrosis and contributing to cardiac dysfunction. Advances in Multimodal single-cell profiling, such as scRNA-seq and scATAC-seq, provide deeper insights into DCM's unique cell states and molecular landscape for targeted therapeutic interventions.
METHODS: Single-cell RNA and ATAC data from 10x Multiome libraries were processed using Cell Ranger ARC v2.0.1. Gene expression and ATAC data underwent Seurat and Signac filtration. Differential gene expression and accessible chromatin regions were identified. Transcription factor activity was estimated with chromVAR, and Cis-coaccessibility networks were calculated using Cicero. Coaccessibility connections were compared to the GeneHancer database. Gene Ontology analysis, biological process scoring, cell-cell communication analysis, and gene-motif correlation was performed to reveal intricate molecular changes. Immunofluorescent staining utilized various antibodies on paraffin-embedded tissues to verify the findings.
RESULTS: This study integrated scRNA-seq and scATAC-seq data obtained from hearts of WT and DCM mice, elucidating molecular changes at the single-cell level throughout the diabetic cardiomyopathy progression. Robust and accurate clustering analysis of the integrated data revealed altered cell proportions, showcasing decreased endothelial cells and macrophages, coupled with increased fibroblasts and myocardial cells in the DCM group, indicating enhanced fibrosis and endothelial damage. Chromatin accessibility analysis unveiled unique patterns in cell types, with heightened transcriptional activity in myocardial cells. Subpopulation analysis highlighted distinct changes in cardiomyocytes and fibroblasts, emphasizing pathways related to fatty acid metabolism and cardiac contraction. Fibroblast-centered communication analysis identified interactions with endothelial cells, implicating VEGF receptors. Endothelial cell subpopulations exhibited altered gene expressions, emphasizing contraction and growth-related pathways. Candidate regulators, including Tcf21, Arnt, Stat5a, and Stat5b, were identified, suggesting their pivotal roles in DCM development. Immunofluorescence staining validated marker genes of cell subpopulations, confirming PDK4, PPARγ and Tpm1 as markers for metabolic pattern-altered cardiomyocytes, activated fibroblasts and endothelial cells with compromised proliferation.
CONCLUSION: Our integrated scRNA-seq and scATAC-seq analysis unveils intricate cell states and molecular alterations in diabetic cardiomyopathy. Identified cell type-specific changes, transcription factors, and marker genes offer valuable insights. The study sheds light on potential therapeutic targets for DCM.