anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
PROBLEM TO BE SOLVED: To provide a new compound that is useful in the treatment of central nervous system disorder. SOLUTION: This compound is represented by formula I (n, m are each 1, 2; p is 1-6; q is 0, 1-3; R<1> and R<2> are each H or the like; R<3> to R<5> are each H or the like; R<6> is a 1-4C alkyl; dotted line means a double bond; F bonds to the 6 or 7 position), its salt or ester, typically a compound of formula II. This new compound is obtained by reaction of a compound of formula III with an aldehyde equivalent of formula IV (X is a halogen). The aldehyde is prepared by oxidizing a suitable terminal alkene with ozone or the like followed by reductive amination of the aldehyde group with sodium cyanoborohydride or using triacetoxycyanoborohydride and a compound of formula III, preferably in a polar solvent as acetonitrile in the presence of a base as sodium iodide at 50-150 deg.C. The new compound of formula I has an effective action of activating the central nervous system.  The daily dose for treating an adult person is 0.5-100 mg.
Coronavirus disease-2019 (COVID-19) can cause acute ischemic stroke (AIS) due to large vessel occlusion (LVO). Some cases of COVID-19-related LVO are known to be resistant to mechanical thrombectomy and have different characteristics from non-COVID-19-related LVO. Inflammation of the occluded arterial wall is suspected as one of the causes of such differences, but the exact mechanism is not fully understood. A 52-year-old man suffered from AIS due to left vertebral artery (VA) occlusion during the recovery period after mild COVID-19. Successful recanalization of the left VA was achieved with antithrombotic therapy, but a late and reversible edematous lesion appeared in part of the brainstem adjacent to the left VA, with abnormal enhancement in both the left VA wall and medulla oblongata on postcontrast magnetic resonance imaging. We suggest that the left VA wall inflammation, induced by COVID-19, caused the ischemic stroke and extended to the brainstem, and an incidental thrombosed unruptured aneurysm of the left VA accelerated these changes. This case provides the first evidence of LVO after COVID-19 in which the pathological conditions in the brainstem adjacent to the affected artery could be observed with neuroimaging and inflammation of the arterial wall was indirectly confirmed. Physicians should be aware that unconventional ischemic stroke may develop in some patients during the recovery period after COVID-19.
Analogs related to oleamide are employed for potentiating the 5-HT2A and 5-HT1A responses to serotonin (5-HT). With respect to the potentiation of the 5-HT2A receptor response, it is disclosed that, of the naturally occurring fatty acids, the primary amide of oleic acid (oleamide) is the most effective potentiating agent of serotonin and that the potentiating activity of oleamide analogs is highly dependent upon their structural features. In particular, the presence, position, and stereochemistry of the 9- cis double bond is required and even subtle structural variations reduce or eliminate activity. Secondary or tertiary amides may replace the primary amide but follow a well-defined relationship requiring small amide substituents suggesting that the carboxamide serves as a hydrogen bond acceptor but not donor. Alternative modifications at the carboxamide as well as modifications of the methyl terminus of the hydrocarbon region spanning the carboxamide and double bond typically eliminate activity. With respect to the potentiation of the 5-HT1A  receptor response, it is disclosed that the potentiation activity of oleamide analogs is more tolerant and accommodates a wider range of structural modifications. One genus of analogs is disclosed that inhibits rather than potentiates the 5-HT2A, but not the 5-HT1A, receptor response. Such analogs permit the selective modulation of serotonin receptor subtypes and have opposing effects on the different subtypes.
BACKGROUND: Clinical trials have shown the kidney-protective benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i). However, their real-world impact, particularly across varying levels of albuminuria, remains less well understood. This study aimed to evaluate the association of SGLT2i, compared with other oral glucose-lowering drugs, with end-stage kidney disease (ESKD) progression in patients with type 2 diabetes and chronic kidney disease (CKD) stratified by urine albumin-to-creatinine ratio (UACR) levels.
METHODS: Using data from a national database spanning from 2016 to 2021, the study included patients with type 2 diabetes and CKD with estimated glomerular filtration rates (eGFRs) below 60 mL/min/1.73 m2 and who started on SGLT2i or other oral glucose-lowering drugs. Patients were stratified into groups by UACR ≥300 mg/g and <300 mg/g. Propensity score matching was used to minimize confounding, and progression to ESKD was evaluated using competing risks and Cox proportional-hazards models. All-cause mortality was also analyzed.
RESULTS: Following propensity score matching, 18,514 patients in the severely increased albuminuria group (UACR ≥300 mg/g) were tracked, with 2.6% progressing to ESKD over 3 years. In contrast, only 0.3% of the 26,946 patients with UACR <300 mg/g progressed to ESKD. SGLT2i use was associated with a 30% reduction in risk of ESKD progression, compared with the use of other oral glucose-lowering drugs, in the severely increased albuminuria group (hazard ratio[HR]: 0.70, 95% confidence interval [CI]: 0.61-0.80). In the lower albuminuria group, no significant association was evident, though there was a nonsignificant trend toward protection over time. A consistent reduction in mortality risk was observed across all albuminuria levels.
CONCLUSIONS: SGLT2i are associated with a reduction in the progression to ESKD among patients with severely increased albuminuria, with less pronounced effects observed in those with lower albuminuria levels, suggesting variability in renal outcomes based on albuminuria severity. The consistent survival benefit across all albuminuria levels supports the potential utility of SGLT2i in diabetes and CKD treatment strategies, emphasizing the need for more targeted research.
This is a Phase 1, randomized (study drug assigned by chance), open-label (all people know the identity of the intervention), 2 way crossover (method used to switch participants from one study group change to treatment group), single-dose study in healthy participants. The study will consist of 3 phases: Screening Phase (Day -21 to Day -2), Treatment Phase (consists of 2 single-dose treatment period, either JNJ-42756493 capsule or JNJ-42756493 tablet) and Follow-up Phase (12-14 days after last dose). All the eligible participants will be randomly assigned to 1 of the 2 treatment sequences to ensure that they receive both of the treatments, 1 in each period. Each treatment regimen will be separated by a washout period of at least 15 days. Blood samples will be collected for evaluation of pharmacokinetics at pre-dose and post-dose of study treatment. Relative bioavailability of two dosage form of JNJ-42756493 (test and reference) will be evaluated primarily. Participants' safety will be monitored throughout the study.
The pressent invention relates to the method and system for feeding the macromolecular drug through the mucous membrane into buccal mucous. The system consists of internal drug, reinforcer and polymer layer, one surface of it is suitable to contact and adhere to the buccal mucous tissue, the opposite surface to contact and adhere the above insert layer. The internal layer contains about 2% to 60% (weight) of bile salt, 5% to 65% (weight) of hydrophilic polymer, and effective amount of macromolecular drug with molecular weight at least 500 daltons. The polyose, polypeptide and protein are optimized macromolecular medicines. The bile salt reinforcer promotes the transportation of the macromolecule such as low molecular weight heparin and calcitonin. The hydroxy-propyl cellulose is the most suitable polymer.
Patients who undergo prostate biopsy for suspected prostate cancer. Each patient would undergo both a portable MRI-registered biopsy and a TRUS-image-fusion biopsy. To reduce the risk of bias between the two modalities, the order of the modality will be randomized 1:1. There will be no blinding of the surgeon.
A 16-year-old girl with fever that appeared after taking the second COVID-19 vaccine presented to the clinic with a serum creatinine of 0.89 mg/dL and C-reactive protein of 6.9 mg/dL. She had proteinuria and microscopic hematuria, with slowly worsening kidney function. Her kidney biopsy showed fibrocellular crescents in seven of nine glomeruli that were observed under light microscopy. Another glomerulus showed endocapillary hypercellularity and mesangial cell proliferation. Electron-dense deposits were significant in the mesangial area, with monoclonal IgG1-κ and C3 deposition by immunofluorescence. The patient was diagnosed with proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) and atypical pathological finding of diffuse crescent formation. The treatment regimen for PGNMID has not yet been established, and the appropriate duration of treatment is unknown. In our case, considering that rituximab acts by binding to CD20 on the surface of B cells through its crystallizable fragment, it was administered in addition to prednisolone, which successfully decreased the proteinuria over time.
The investigators will conduct a randomized, double-blind, sham-controlled trial to determine the efficacy of CES as an add-on treatment for tic disorders (SCATT). The study will be conducted at an outpatient, single-center academic setting. A total of 100 patients aged 6 to 17 years with tic disorders and lack of clinical response to 4 weeks' pharmacotherapy will be enrolled. Patients will be randomly into 2 groups and given 4 weeks' treatment, including 40 daily 30-minute sessions of active CES(500μA\~2mA) or sham CES(lower than 100μA) on weekdays. Change in Yale Global Tic Severity Scale (YGTSS) is considered to be the primary outcome. The secondary outcome is the changes in Clinical Global Impression (CGI) and Hamilton Anxiety Scale (HAMA). Assessments will be performed at baseline, week 2, week 4 and week 8. Adverse events(AE) will be also evaluated.
Compositions and methods for treating ear infections are disclosed. More specifically, these methods may refer to treatment of internal otitis using an otic composition, such as otic gel for animals and humans. Poloxamer otic gel may be in liquid state at room temperature and may change to gel at about temperature (64° F.) as poloxamer otic gel reaches body temperature, because of the thermo-reversible properties. Consequently, poloxamer otic gel may be an effective treatment in animals and humans, where poloxamer otic gel may reach otitis affected site and remain there for a longer period of time. Additionally, poloxamer otic gel may include APIs such as antifungals, antibiotics and corticosteroids, among others. Furthermore, poloxamer otic gel may be instilled inside the ear, employing calibrated delivery device into the vertical ear canal in order to reach the horizontal ear canal, without puncturing the tympanic membrane.
PURPOSE: To provide a formation method for pure hydroxyl apatite of non- porous nature by attaching a layer of α- or β-tricalcium-phosphate(TCP) onto a body made of metal or non-metallic material, and allowing this layer to react with water at a high temp. CONSTITUTION: To form a layer of hydroxyl apatite(HA) on a body made of metal or non-metallic material as an implantation, first thereto pure tricalcium-phosphate(TCP) is attached by means of hot spray, vacuum evaporation, or sputtering, and thereby a pure TCP layer of high density is formed without decomposition products. If α-TCP (high temp. denaturing) has occurred because of high cooling velocity, it is possible that β-TCP is produced from α-TCP in the subsequent heat treatment. The obtained β- or α-TCP is converted perfectly into HA by heating underwater the implantation structure, wherein the water tamp. is regulated according to possibility of the device, preferably ranging from 60 to 90 deg.C. The layer converted into HA has a very high histocompatibility to enable quick absorption and healing.
Participants randomized into the Standard arm will have a goal of SBP \<140 mm Hg. Intensify therapy if SBP ≥160 mmHg @ 1 visit; ≥140 mmHg @ 2 consecutive visits; Down-titration if SBP \<130 mmHg @ 1 visit; \<135 mmHg @ 2 consecutive visits.
OBJECTIVE: This study aimed to investigate the clinical characteristics of patients with complications following inadequate primary orbital fracture repair and to evaluate surgical outcomes of secondary revision orbital reconstruction.
METHODS: The authors retrospectively reviewed data from 41 patients who underwent revision orbital reconstruction by a single surgeon following complications from primary orbital fracture repair performed elsewhere. Clinical characteristics, including enophthalmos, exophthalmos, diplopia, ocular motility limitation, epiphora, infraorbital hypoesthesia, infection, eyelid malposition, lagophthalmos, hypoglobus, and compressive optic neuropathy, were assessed. Surgical outcomes of revision surgery were evaluated to determine improvements in clinical deficits and postoperative patient satisfaction.
RESULTS: The most common postoperative complications of primary orbital fracture repair were enophthalmos (n=20/41) and diplopia (n=20/41). The mean time between primary and revision surgeries was 67.2 months (range: 1-276 mo). Revision surgery significantly improved enophthalmos, diplopia (Hess area ratio), epiphora (Munk score), periorbital pain, and exophthalmos ( P =0.003, P =0.001, P <0.001, P <0.001, and P =0.007, respectively) compared to the pre-revision state. In addition, 6 patients experienced improved infraorbital hypoesthesia. Among the 41 patients, 23 were very satisfied, 17 were satisfied, and 1 was neutral after revision orbital reconstruction.
CONCLUSIONS: Our study highlights the positive impact of revision orbital reconstruction in addressing complications from inadequate primary orbital fracture repair. Surgeons should consider revision surgery to address clinical deficits following prior surgery, especially when anatomic abnormalities are evident in imaging studies, regardless of the time lapse since the initial surgery or concerns about tissue fibrosis and fat atrophy.
Fibrosis, a pathological increase in extracellular matrix proteins, is a significant health issue that hinders the function of many organs in the body, in some cases fatally. In the heart, fibrosis impacts on electrical propagation in a complex and poorly predictable fashion, potentially serving as a substrate for dangerous arrhythmias. Individual risk depends on the spatial manifestation of fibrotic tissue, and learning the spatial arrangement on the fine scale in order to predict these impacts still relies upon invasive ex vivo procedures. As a result, the effects of spatial variability on the symptomatic impact of cardiac fibrosis remain poorly understood. In this work, we address the issue of availability of such imaging data via a computational methodology for generating new realisations of cardiac fibrosis microstructure. Using the Perlin noise technique from computer graphics, together with an automated calibration process that requires only a single training image, we demonstrate successful capture of collagen texturing in four types of fibrosis microstructure observed in histological sections. We then use this generator to quantitatively analyse the conductive properties of these different types of cardiac fibrosis, as well as produce three-dimensional realisations of histologically-observed patterning. Owing to the generator's flexibility and automated calibration process, we also anticipate that it might be useful in producing additional realisations of other physiological structures.
•The blocks techniques:

* Group I: Thoracic paravertebral block group (TPVB group n=15) These patients will receive single ipsilateral ultrasound-guided thoracic paravertebral block. TPVB will be performed with the patient in the sitting position at the level of the 4th thoracic vertebra under complete aseptic precaution with the probe in a vertical position approximately 2.5-3 cm lateral to the midline. The midpoint of the transducer is to be placed in a longitudinal paramedian plane between two transverse processes. Both transverse processes should be visualized, with the superior costo-transverse ligament and the pleura visible in between .An 18-20 gauge Tuohy needle will be introduced in a cephalad direction. The tip of the needle will be advanced under direct visualization until it pierces the superior costo-transverse ligament. the investigators will inject small aliquots of normal saline intermittently as the investigators advance the needle to confirm the position of the tip. When the needle tip is located immediately above the pleura, the needle is aspirated to confirm the absence of blood or air. After this, 15-20 cc of bupivacaine 0.25% will be injected. Spread of local anaesthetic with depression of the pleura will be clearly visualized. The extent of local anaesthetic spread should be evaluated by moving the ultrasound probe superiorly and inferiorly.
* Group II :Serratus anterior plane block group (SAP group n= 15) These patients will receive serratus anterior plane block. The SAP block will be performed while the patient is in the supine position by using a linear US probe of high frequency (6-13 MHz) after sheathing. The probe will be placed over the mid-clavicular region of the thoracic cage in a sagittal plane. The ribs will be counted inferiorly and laterally, until the 5th rib is identified in the midaxillary line. The latissimus dorsi (superficial and posterior), teres major (superior) and serratus muscles (deep and inferior) will be then easily identifiable by ultrasound overlying the fifth rib. The needle (Stimuplex, B Braun, Germany 22-G, 50-mm) will be introduced in-plane with respect to the ultrasound probe from supero-anterior to postero-inferior. Under continuous ultrasound guidance, the investigators will inject 20 cc of bupivacaine 0.25%. The sensory level will be tested with pin prick and ice pack before induction of general anesthesia
Patients will be monitored with routine monitoring under operating room conditions. After the patient's baseline VAS score and vital signs are recorded, patients will be intubated after induction of general anesthesia. After the site is cleaned, pericapsular nerve block (PENG) will be applied under USG guidance. After the procedure, the patient will be transferred to the surgical team for positioning. Blood pressure and pulse values will be recorded after the procedure and at the 30th minute of surgery. After the patients wake up, another anesthesiologist in the recovery unit will rate the pain of patients in both groups on a scale of 0-10, using the Visual Analogue Scale (VAS) to describe their pain intensity. Heart rates and noninvasive blood pressures of patients taken to the recovery unit will be measured and recorded.
Glembatumumab vedotin once every three weeks (q3w) by 90-minute intravenous (IV) infusion, until disease progression or intolerance. The Dose-Limiting Toxicity (DLT) evaluation period for determination of the appropriateness of dose-escalation will be through the end of the second treatment cycle.
BACKGROUND: lNUAK1 is strongly associated with organ fibrosis, but its causal mechanism for modulating lipid metabolism and hepatic inflammation underlying MASH has not been fully clarified.
METHOD: In our study, human liver tissues from patients with MASH and control subjects were obtained to evaluate NUAK1 expression. MASH models were established using C57BL/6 mice. Liver damage and molecular mechanisms of the NUAK1-Caspase 6 signaling were tested in vivo and in vitro.
RESULTS: In the clinical arm, NUAK1 expression was upregulated in liver samples from patients with MASH. Moreover, increased NUAK1 was detected in mouse MASH models. NUAK1 inhibition ameliorated steatohepatitis development in MASH mice accompanied by the downregulation of hepatic steatosis and fibrosis. Intriguingly, NUAK1 was found to facilitate Caspase 6 activation and trigger pyroptosis in MASH-stressed livers. Disruption of hepatocytes Caspase 6 decreased MASH-induced liver inflammation with upregulated TAK1 but diminished RIPK1. Moreover, we found that NUAK1/Caspase 6 axis inhibition could accelerate the interaction between TAK1 and RIPK1, which in turn led to the degradation of RIPK1.
CONCLUSIONS: In summary, our study elucidates that NUAK1-Caspase 6 signaling controls inflammation activation in MASH through the interaction between TAK1 and RIPK1, which is crucial for controlling pyroptosis and promoting the progression of MASH.
PENS and TENS have been reported with analgesic effect in patients with pain, including cancer pain, lower back pain, neck pain, stomachache and so on. Effect and mechanism of PENS on pain relieving has been widely researched. With additional electrical stimulation in certain frequency and intensity to conventional acupuncture, pain controlling effect has been largely enhanced. However, invasive operation limits its application and acceptability, especially on pancreatic cancer. TENS is an advanced technique generated from PENS, which is much more welcome for its noninvasive character. Further more, its analgesic effect on cancer pain has been proved by several multi-central, randomized, clinical trials.
AIMS: This study evaluates long-term changes in physical activity and its associations with various predictors after a behavior change program at the Norwegian Healthy Life Centers.
BACKGROUND: Physical activity is recommended and is part of public health strategies to prevent noncommunicable diseases.
METHODS: This longitudinal cohort, based on a controlled randomized trial, studies a population of 116 Healthy Life Center participants in South-Western Norway who wore SenseWear Armbands to measure time spent in moderate to vigorous physical activity and sedentary time based on metabolic equivalents. The measurements were obtained at baseline, immediately post-intervention, and 24 months after baseline. Linear mixed model analyses were performed to assess predictors for change in physical activity and sedentary time.
FINDINGS: High physical activity levels at baseline were maintained during the 24-month study period. Young, male participants with good self-rated health, utilizing local PA facilities were most active, and young participants utilizing local facilities were also less sedentary. The participants with higher levels of education were less active initially but caught up with the difference during follow-up. A high degree of controlled regulation, characterized by bad conscience and external pressure, predicted more sedentary behavior and a trend toward being less physically active. Autonomous motivation was associated with less time spent on sedentary behaviors. People with high self-efficacy for physical activity were more sedentary initially but showed a reduction in their sedentary behavior.The study supports the importance of attending local training facilities and adopting motivation for behavioral change that is not based on guilt and external rewards. Interventions aimed at improving physical activity among people at risk for noncommunicable diseases benefit from habitual use of local training facilities, strengthening their self-perceived health and the development of internalized motivation. However, it has not been shown to mitigate social health disparities.