anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Pericytes, a specific type of mesenchymal cell that surround the basement membrane of pulmonary venules and capillaries. They are crucial pathological features observed in individuals with the severe lung disease of pulmonary fibrosis (PF). The presence of pericytes leads to inflammation and fibrosis in the lung interstitium and alveolar space due to the release of various cytokines and chemokines. Pericytes also stimulate the proliferation and activation of fibroblasts, thereby promoting the progression of PF. Previous studies examining the mechanism of action of pericytes have primarily focused on cell signal transduction pathways, cell growth and death processes, and the synthesis and breakdown of extracellular matrix (ECM). Notably, the transforming growth factor-β (TGF-β) and Wnt signaling pathways have been associated with the action of pericytes in driving the progression of PF. It is therefore clear that pericytes play an essential role in the development of PF, while also offering possible avenues for targeted therapeutic intervention against this condition. The current article provides a comprehensive review on how pericytes contribute to inflammatory responses, as well as their importance for understanding the mechanism of PF. In addition, this review discusses the potential use of pericyte-targeted approaches for the treatment of patients affected by this debilitating lung disease.
The objective of this study is to understand the effects of anxiety on reward responsiveness in adolescents with anorexia nervosa (AN), and how this interaction predicts behavioral outcome subsequent to intensive treatment. Investigators plan to test, for the first time, how acute activation of threat related emotional circuitry reciprocally alters reward circuit activity, and to what degree this modulation predicts post treatment relapse. The severity of AN, its resistance to intervention, potential for quick return of illness, risk for long-term chronicity, and premature death, are well appreciated. Various forms of intensive treatment may succeed in at least partial weight restoration, yet early relapse is unusually high. The appearance early in life of prodromal anxiety phenotypes in individuals who subsequently develop AN is well documented and nearly universal. Anxiety proneness in concert with rigid self-discipline may therefore be predisposing substrates for sudden morbid apprehension about weight gain, and may contribute to subsequent behaviors including vigilant scrutiny of body size and shape and inflexible cognitive patterns regarding food and eating. In parallel, persons with restricting-type AN typically exhibit unease and reticence when exposed to novel, high reward environments. Most studies have found low fun-seeking, low novelty seeking, and reduced reward responsiveness in those with AN. In line with these observations, functional magnetic resonance imaging (fMRI) studies demonstrate aberrant reward sensitivity and reward circuit activation. However the interaction of anxiety and reward circuits has never been interrogated. There is substantial evidence of distinct yet overlapping neural systems mediating approach/reward and avoidance/anxiety, which are integrated in balancing and switching between behaviors related to the predominant valence state. Thus investigators posit that high degrees of reactivity of cortico-limbic circuits underlying anxiety may contribute mechanistically and functionally to diminished initial responsiveness to reward stimuli. This may translate clinically to lower motivation to engage in outpatient treatment - in effect, a lower drive to change behaviors and thought patterns necessary for maintaining gains or improving, based on expectancy of benefits of future outcome. The dynamic interaction between reward and anxiety systems in AN, and how dysregulation of connectivity within and between these systems mediates behavioral outcomes, has not previously been tested. Investigators will investigate this interaction using sequential fMRI paradigms and novel integrated functional-by-structural connectivity in individuals who have completed standard treatment on an eating disorder unit. Investigators will then investigate how this neural circuitry may predict degree of relapse during the subsequent 6 months.
In recent years, with the advance of research, the role of tumor-associated neutrophils (TANs) in tumors has become a research hotspot. As important effector cells in the innate immune system, neutrophils play a key role in the immune and inflammatory responses of the body. As the first line of defense against bacterial and fungal infections, neutrophils have the ability to kill invading pathogens. In the pathological state of malignant tumors, the phenotype of neutrophils is altered and has an important regulatory function in tumor development. The C-X-C motif chemokine receptor 2(CXCR2) is a key molecule that mediates the migration and aggregation signaling pathway of immune cells, especially neutrophils. This review focuses on the regulation of CXCR2 on TANs in the process of tumorigenesis and development, and emphasizes the application significance of CXCR2 inhibitors in blocking the migration of TANs to tumors.
In animal studies (rats, mice, dogs), the kidney was the principal organ for toxicity. (In the following, comparisons of animal dosing to recommended human dosing are based on body surface area and a 2.4 grams per day dose for a 60 kg person.) 

Mesalamine causes renal papillary necrosis in rats at single doses of approximately 750 mg/kg to 1000 mg/kg (approximately 3 to 4 times the recommended human dose based on body surface area). Doses of 170 and 360 mg/kg/day (about 0.7 and 1.5 times the recommended human dose based on body surface area) given to rats for six months produced papillary necrosis, papillary edema, tubular degeneration, tubular mineralization, and urothelial hyperplasia. 

In mice, oral doses of 4000 mg/kg/day mesalamine (approximately 8 times the recommended human dose based on body surface area) for three months produced tubular nephrosis, multifocal/diffuse tubulo-interstitial inflammation, and multifocal/diffuse papillary necrosis. 

In dogs, single doses of 6000 mg (approximately 8 times the recommended human dose based on body surface area) of delayed-release mesalamine tablets resulted in renal papillary necrosis but were not fatal. Renal changes have occurred in dogs given chronic administration of mesalamine at doses of 80 mg/kg/day (1.1 times the recommended human dose based on body surface area).
The aim of the research was to evaluate the influence of antagonists of specific beta-adrenergic receptor subtypes on bowel motility following abdominal surgery in rat model of postoperative ileus. Bowel motility was measured by the intestinal transit of Evans blue introduced via orogastric tube after surgical procedures of skin incision, laparotomy and laparotomy with gut manipulation. Male rats were given individual adrenergic receptor subtypes antagonists intraperitoneally, and the influence of administered agents on intestinal transit of Evans blue was then evaluated. No statistically significant differences in the length of intestine in tested rats were observed. Propranolol administered prior to surgical procedure has shown protective effect on Evans blue migration in rats undergoing laparotomy and gut manipulation. Intestinal dye transit for propranolol doses of 10, 30 and 45 mg/kg was 18.00 ± 1.88c m, 23.75 ± 1.71 cm and 22.5 ± 2.43 cm, respectively, and for last two doses, statistically significant increase of dye passage was noted, compared to Evans blue transit of 11.00 ± 2.43 cm in the control group. No acceleration of dye migration was seen following administration of beta1-, beta2- and beta3-selective adrenergic receptor antagonist metoprolol, ICI 118.551 and SR58894A, respectively. Our research confirmed that propranolol at high doses, as seen by other researchers, improved bowel motility in early phase of postoperative ileus. That slight acceleration of intestinal dye transit after surgery with gut manipulation is rather connected with membrane-stabilizing action, than the receptor blocking effect, as this effect was not observed after the application of selective antagonists of respective subtypes of beta-adrenergic receptor.
OBJECTIVES: The EQ-5D-5L is a generic health utility instrument for measuring health-related quality of life (HRQoL), with self-report and proxy report versions for children (EQ-5D-Y-5L). Children with intellectual disability (ID) are a heterogeneous population whose impairments and comorbidities place them at risk of poor HRQoL. This study aimed to describe the content validity and suitability for children with ID of a proxy report version of the EQ-5D-Y-5L as seen by their caregivers.
METHODS: A proxy report EQ-5D-Y-5L was administered to caregivers of children with ID. Using cognitive think-aloud interviewing, participants were encouraged to provide the reasoning for their choices, assess the questions' relevance, comprehensibility, and comprehensiveness, and comment on the tool's strengths and weaknesses. Qualitative content analysis used both directed (deductive) and conventional (inductive) methods.
RESULTS: There were 28 interviews with 30 caregivers of children with ID (aged 8-22 years, 17 boys, with autism spectrum disorder, cerebral palsy, Down syndrome, and rare genetic disorders). The EQ-5D-Y-5L was considered clear, concise, and largely relevant, but insufficiently comprehensive for this population. Interviewees sought clarification of the definition of HRQoL, whether it included unchanging impairments (vs fluctuating health states), and what basis of comparison to use (child or peer). Many interviewees suggested inclusion of questions for other domains, including communication and social engagement, equipment and human supports required, and a wider range of mental health questions.
CONCLUSIONS: The study suggests that further work is required to ensure accurate responses to the EQ-5D-Y-5L from caregivers of children with ID and to describe these children adequately.
A subgroup of 70 pregnant women who will deliver by planned caesarian selected towards either high (N=35) or low (N=35) risk for perinatal depression will undergo brain imaging in addition to the elements of the basic program. The extended imaging program includes functional and structural magnetic resonance imaging, positron emission tomography (PET) and a semistructured interview for depression symptoms (HAM-D17).
Immune thrombocytopenic purpura (ITP) is an uncommon condition resulting from the autoimmune destruction of platelets. A man in his mid-30s, who had received three doses of the SARS-CoV-2 vaccine a year prior, was diagnosed with ITP 3 weeks after contracting COVID-19. Mechanisms of SARS-CoV-2 induced thrombocytopenia may include bone marrow depletion, coagulation consumption, mutations resulting in cytokine release or molecular mimicry leading to autoimmunity. Initial treatment involved glucocorticoids, but the disease course progressed into glucocorticoid-resistant ITP. Subsequently, the patient was diagnosed with ITP refractory to intravenous immunoglobulin, thrombopoietin receptor agonist, rituximab, cyclophosphamide, inhibitors of BTK and SYK, and other pharmacological agents. Despite exhaustive medical interventions, bleeding diathesis and platelet counts worsened, so the patient underwent a splenectomy resulting in the resolution of the thrombocytopenia.
Study Design: Subjects will be ten patients with MDD identified via the Structured Clinical Interview for DSM-IV, manifesting a current major depressive episode of disabling severity, refractory to prolonged treatment trials with conventional medication, electro-convulsive therapy (ECT) and psychotherapy. A marked impact of depression on their health and functional status will be evidenced by major impairment in functioning or potentially severe medical outcomes (repeated hospitalizations, serious suicidal or other self-injurious behavior). They will be recruited from individuals currently seen at our facility or referred by psychiatrists in the community. Patients will be initially screened by a comprehensive review of their psychiatric history, obtained by interview of the patient, family and treating psychiatrist and/or psychologist, as well as by obtaining and reviewing all available records of previous psychiatric treatment. The available generally-accepted alternative treatments for depression are pharmacologic therapy, psychotherapy, and ECT. Failed trials of multiple proven pharmacologic treatments, an adequate course of psychotherapy, and an adequate course of bilateral ECT (or inability to tolerate an adequate ECT trial) are inclusion criteria for all candidates who are considered for this study. However, as alternatives to participation in this study, candidates may undertake additional trials of potentially beneficial novel combinations of medication and psychotherapy, or they may undertake trials of novel interventions lacking definitive evidence of efficacy in severe depression (e.g., light therapy, herbal therapy, transcranial magnetic stimulation, vagal nerve stimulation). The protocol was designed to include four phases. All patients will enter these phases in the same sequence. The experimental design is illustrated in the timeline in Figure 1. Surgical implantation will be followed by: 1) Baseline Phase (a 1 month period with no stimulation); 2) Variable Staggered Phase (blinded stimulation onset starting from 1 month to 3 months post implant, with optimal parameter determination during this time ; 3) Initial Chronic Phase (blinded bilateral stimulation, lasting at least three months) (see below); 4) Continuation Phase (unblinded active bilateral or unilateral stimulation to maximize clinical response) Protocol overview and design: We propose a clinical study of medial forebrain bundle DBS as a treatment in 10 patients with treatment refractory depression (TRD). Data from the University of Bonn indicates that surgical lesions of the medical forebrain bundle can produce therapeutic benefits in patients with depressive disorders, and suggest that DBS at the same site may also reduce symptomatology in these TRD patients (Schaepfer, 2013). Depression affects up to 10% of the US population and of those at least 10-15% do not benefit from therapies hence why we must explore new treatments. The Percept™ PC system manufactured by Medtronic Neurological will be used in this study. Those identified as TRD patients will then be enrolled in a clinical pilot study investigating DBS, targeting the MFB.
The use of outpatient parenteral antimicrobial therapy (OPAT) for children has several advantages, including reduced length of hospital stay and costs. A reliable vascular access is key to delivering safe and effective pediatric OPAT. In recent years, midline catheters (MC) have been increasingly used for short-term intravenous antibiotic therapy in children. However, there are no studies investigating the use of MCs in the OPAT setting. The main aim of this paper was to evaluate the success and complications of using MCs for pediatric OPAT. This was a retrospective cohort study from a tertiary academic pediatric hospital. All MCs inserted at the hospital and used for OPAT were eligible for study inclusion. The primary objective was to describe the percentage of patients able to complete OPAT without the need for additional venous access. Forty-one MCs were included in the study. Patient mean (SD) age was 5.9 (4.9) years. In 31 cases (76%, 95% CI 62-86%), the iv therapy could be successfully completed using only the MC. Imbalances between the groups suggested unfavorable outcome for saphenous vein catheters as well as for shorter and smaller-sized catheters. Fourteen patients (34%) were subjected to a MC-related complication. Pain on injection in the MC was the most frequent complication (n = 10, 24%).    Conclusion: Midline catheters could be an alternative to central venous access for pediatric OPAT. Avoiding saphenous vein insertion and using longer and larger-sized catheters could increase MC success rate. No severe MC-related complication was found. Further randomized studies comparing different catheter types are needed. What is Known: • For selected patients, pediatric outpatient parenteral antimicrobial therapy (OPAT) is safe and provides health-economic, psychosocial, and medical advantages compared to in-hospital care. • A reliable venous access is one of the key factors to the success of OPAT, but this can be a challenge in children. What is New: • Using midline catheters, 76% of patients could complete their intended iv therapy without the need for additional venous access. Avoiding saphenous vein insertion and using longer and larger-sized catheters could increase the success rate. • Thirty-four percent of catheters were subject to some kind of complication, the most common being pain on injection in the catheter.
Repetitive Transcranial Magnetic Coil Stimulation (rTMS) treatment in Alzheimer's disease. The Magstim Rapid2 stimulator with a peak magnetic field of 0.5-3.5 Tesla at 100% output was used over the right and left dorsolateral prefrontal cortex. Patients received 4 sessions of rTMS over 2 weeks, lasting approximately 30 minutes, 2 consecutive days a week for 2 weeks.
Participants will receive ACR16 45 mg capsule once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 12), ACR16 45 mg capsule will be taken twice daily (BID) as 2 separate doses (total dose: 90 mg).
Bruton tyrosine kinase inhibitors (BTKis) that target B-cell receptor signaling have led to a paradigm shift in chronic lymphocytic leukemia (CLL) treatment. BTKis have been shown to reduce abnormally high CLL-associated T-cell counts and the expression of immune checkpoint receptors concomitantly with tumor reduction. However, the impact of BTKi therapy on T-cell function has not been fully characterized. Here, we performed longitudinal immunophenotypic and functional analysis of pretreatment and on-treatment (6 and 12 months) peripheral blood samples from patients in the phase 3 E1912 trial comparing ibrutinib-rituximab with fludarabine, cyclophosphamide, and rituximab (FCR). Intriguingly, we report that despite reduced overall T-cell counts; higher numbers of T cells, including effector CD8+ subsets at baseline and at the 6-month time point, associated with no infections; and favorable progression-free survival in the ibrutinib-rituximab arm. Assays demonstrated enhanced anti-CLL T-cell killing function during ibrutinib-rituximab treatment, including a switch from predominantly CD4+ T-cell:CLL immune synapses at baseline to increased CD8+ lytic synapses on-therapy. Conversely, in the FCR arm, higher T-cell numbers correlated with adverse clinical responses and showed no functional improvement. We further demonstrate the potential of exploiting rejuvenated T-cell cytotoxicity during ibrutinib-rituximab treatment, using the bispecific antibody glofitamab, supporting combination immunotherapy approaches.
FIELD: medicine, pharmacology, pharmacy. SUBSTANCE: invention relates to pharmaceutical preparation of omeprazole. Pharmaceutical preparation covered by enterosoluble envelope as an active component comprises compound taken among group consisting of omeprazole, omeprazole alkaline salt, (-)- enantiomer omeprazole and (-)-enantiomer omeprazole alkaline salt. This preparation comprises core comprising an active component and, possibly, alkaline reagent being an active component is in the mixture with pharmaceutically acceptable excipient, as such, binding agent and separating layer and enterosoluble enveloper layer are applied on indicated core material. For preparing pharmaceutical preparations hydroxypropylmethylcellulose with the definite cloud point is used. Except for, invention describes methods for preparing and usage of the claimed preparations in medicine. Invention provides preparing preparation useful for oral administration of omeprazole. EFFECT: improved preparing methods, valuable medicinal and pharmaceutical properties of preparation. 13 cl, 1 tbl, 3 dwg
BACKGROUND: Extracorporeal shock wave therapy (ESWT) is reportedly effective for improving spasticity and motor function in children with cerebral palsy (CP). Because late-stage Rett syndrome has a similar presentation, this study aimed to investigate the effects of ESWT on these two diseases.
MATERIAL AND METHODS: Patients diagnosed with spastic CP and Rett syndrome received 1500 impulses of ESWT at 4 Hz and 0.1 mJ/mm2, on their spastic legsonce weekly for a total of 12 weeks. Outcomes were assessed before and 4 and 12 weeks after ESWT. Clinical assessments included the Modified Ashworth Scale (MAS), passive range of motion (PROM), and Gross Motor Function Measure 88 (GMFM-88). Ultrasonographic assessments included muscle thickness, acoustic radiation force impulse (ARFI), and strain elastography.
RESULTS: Fifteen patients with CP and six with Rett syndrome were enrolled in this study. After ESWT, patients with CP showed significant clinical improvement in the MAS (P = 0.011), ankle PROM (P = 0.002), walking/running/jumping function (P = 0.003), and total function (P < 0.001) of the GMFM-88. The patients with Rett syndrome showed improved MAS scores (P = 0.061) and significantly improved total gross motor function (P = 0.030). Under ARFI, patients with CP demonstrated decreased shear wave speed in the gastrocnemius medial head (P = 0.038). Conversely, patients with Rett syndrome show increased shear-wave speeds after ESWT.
CONCLUSION: Our study provides evidence that a weekly course of low-dose ESWT for 12 weeks is beneficial for children with both CP and Rett syndrome, with the clinical effects of reducing spasticity and improving the gross motor function of the lower limbs. The ARFI sonoelastography reveals improvement of muscle stiffness in patients with CP after ESWT, but deteriorated in patients with Rett syndrome. The diverse therapeutic response to ESWT may be caused by the MECP2 mutation in Rett syndrome, having a continuous impact and driving the pathophysiology differently as compared to CP, which is secondary to a static insult. Trial registration IRB 201700462A3. Registered 22March 2017, https://cghhrpms.cgmh.org.tw/HRPMS/Default.aspx .
Activity-dependent neuroprotective protein (ADNP) is essential for neurodevelopment and de novo mutations in ADNP cause the ADNP syndrome. From brain pathologies point of view, tauopathy has been demonstrated at a young age, implying stunted development coupled with early/accelerated neurodegeneration. Given potential genotype-phenotype differences and age-dependency, we have assessed here a cohort of 15 individuals (1-27-year-old), using 1-3 longitudinal parent (caretaker) interview/s (Vineland 3 questionnaire) over several years. Our results indicated developmental delays, or even developmental arrests, coupled with potential spurts of development at early ages. Severe outcomes correlated with the truncating high impact mutation, in other words, the remaining mutated protein length as well as with the tested individual age, corroborating the hypothesis of developmental delays coupled with accelerated aging. A significant correlation was noted between mutated protein length and communication, implying a high impact of ADNP on communicative skills. Additionally, correlations were discovered between the two previously described epi-genetic signatures in ADNP emphasizing aberrant acquisition of motor behaviors, with truncating mutations around the nuclear localization signal being mostly affected. Finally, all individuals seem to acquire an age equivalent of 1-6 years, requiring disease modification treatment, such as the ADNP-derived drug candidate, NAP (davunetide), which has recently shown efficacy in women suffering from the neurodegenerative disorder, progressive supranuclear palsy (PSP), a late-onset tauopathy.