anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
BACKGROUND: Alzheimer's disease (AD) affects approximately 50 million people globally and is expected to triple by 2050. Arctiin is a lignan found in the Arctium lappa L. plant. Arctiin possesses anti-proliferative, antioxidative and anti-adipogenic.
OBJECTIVES: We aimed to explore the potential therapeutic effects of Arctiin on rats with AD by evaluating the expression of TLR4, NLRP3, STAT3, TGF-β, cyclin D1, and CDK2.
METHODS: AD was induced in rats by administering 70 mg/kg of aluminum chloride through intraperitoneal injection daily for six weeks. After inducing AD, some rats were treated with 25 mg/kg of Arctiin daily for three weeks through oral gavage. Furthermore, to examine the brain tissue structure, hippocampal sections were stained with hematoxylin/eosin and anti-TLR4 antibodies. The collected samples were analyzed for gene expression and protein levels of TLR4, NLRP3, STAT3, TGF-β, cyclin D1, and CDK2.
RESULTS: In behavioral tests, rats showed a significant improvement in their behavior when treated with Arctiin. Microimages stained with hematoxylin/eosin showed that Arctiin helped to improve the structure and cohesion of the hippocampus, which was previously impaired by AD. Furthermore, Arctiin reduced the expression of TLR4, NLRP3, STAT3, TGF-β, cyclin D1, and CDK2.
CONCLUSION: Arctiin can enhance rats' behavior and structure of the hippocampus in AD rats. This is achieved through its ability to reduce the expression of both TLR4 and NLRP3, hence inhibiting the inflammasome pathway. Furthermore, Arctiin can improve tissue fibrosis by regulating STAT3 and TGF-β. Lastly, it can block the cell cycle proteins cyclin D1 and CDK2.
Following a screening period of up to 28 days, subjects will be admitted to the clinical research unit into one of three cohorts. On the morning of Day 1, subjects in cohorts 1, 2, and 3 will receive fasted doses of probe substrate(s) per assigned cohort. On Day 5, Cohort 2 only will receive a second fasted dose of probe substrates. Subjects in cohorts 1, 2, and 3 will receive the final fasted dose of probe substrate(s) on Day 13. Fasted ecopipam administration will begin on Day 5 and will continue through Day 17 at \~2mg/kg for all cohorts. Ecopipam doses will be tapered starting on Day 18 by 25 mg/day increments until subjects are off drug, with final discharge occurring 24 hours after the ecopipam HCl dose has been reduced to 25 mg (Day 21, 23, or 25).
Tuberculosis (TB) is a major cause of morbidity and mortality among children in developing nations. Symptom-based diagnostic criteria are non-specific and culture confirmation is challenging, as sputum samples are often believed to be to too cumbersome to obtain from small children and specimens typically have low yield due to the paucibacillary nature of pediatric TB. Culture confirmation may be obtained in as few as 10% of cases of suspected pediatric TB. For these reasons, the true extent of the (drug-resistant) TB epidemic in children is unknown. Thus, either clinicians begin empiric treatment without diagnosis or no treatment is given at all. Current laboratory methods, if available at all in resource poor settings, employ smears from expectorated sputa or gastric aspirates which have low sensitivity in children. While more rapid diagnostic techniques such as PCR based tests have been developed, there is still poor sensitivity in children. Improving the diagnosis of pediatric TB must focus on better efforts, including more aggressive strategies to uncover disseminated disease.

Culture confirmation of disseminated disease can be obtained from blood, urine, cerebrospinal fluid (CSF), peritoneal and pleural fluid, or purulent material from lymph node aspirates, abscesses or otorrhea. Unfortunately, little is known about the overall yield from these various specimens in children. From pilot data collected among children at NHP, we know that it is feasible to collect and test various bodily fluid specimens for TB culture.

Although WHO guidelines encourage body fluid collection in order to make a diagnosis of TB in children, at present in NHP, blood and urine cultures are not obtained for mycobacterial culture. However, this study seeks to demonstrate that routine investigation of blood and urine will augment the yield of traditional sputum culture for children in whom disseminated disease is more likely. Improved culture confirmation will allow DST and a more accurate description of the drug-resistant TB epidemic for children in the region.
BACKGROUND & AIMS: There is limited information on how the liver-to-gut axis contributes to alcohol-associated liver disease (AALD). We previously identified that high-mobility group box-1 (HMGB1) undergoes oxidation in hepatocytes and demonstrated elevated serum levels of oxidized HMGB1 ([O] HMGB1) in alcoholic patients. Since interleukin-1 beta (IL-1B) increases in AALD, we hypothesized hepatocyte-derived [O] HMGB1 could interact with IL-1B to activate a pro-inflammatory program that, besides being detrimental to the liver, drives intestinal barrier dysfunction.
RESULTS: Alcohol-fed RageΔMye mice exhibited decreased nuclear factor kappa B signaling, a pro-inflammatory signature, and reduced total intestinal permeability, resulting in protection from AALD. In addition, [O] HMGB1 bound and signaled through the receptor for advanced-glycation end-products (RAGE) in myeloid cells, driving hepatic inflammation, intestinal permeability, and increased portal blood lipopolysaccharide in AALD. We identified that [O] HMGB1 formed a complex with IL-1B, which was found in the livers of patients with acute alcoholic hepatitis and mice with AALD. This complex originated from the liver, because it was absent in the intestine when hepatocytes did not produce [O] HMGB1. Mechanistically, the complex bound RAGE in Kupffer cells and macrophages induced a pro-inflammatory program. Moreover, it bound RAGE in intestinal macrophages and epithelial cells, leading to intestinal inflammation, altered intestinal epithelial cell tight junction protein expression, increased intestinal permeability, and elevated portal blood lipopolysaccharide, enhancing AALD pathogenesis.
CONCLUSIONS: We identified a protein complex of liver origin that amplifies the pro-inflammatory feedback loop in AALD; therefore, targeting this complex could have significant therapeutic potential.
The invention relates to methods for treating alopecia, e.g. androgenic alopecia, with an HDAC4 inhibitor, or a pharmaceutically acceptable salt or composition thereof. The invention further relates to methods of treating alopecia, e.g. androgenic alopecia with an HDAC4 inhibitor, e.g., the HDAC4 inhibitor is one or more of a hydroxamic add based HDAC inhibiror, e.g. vorinostat (SAHA), belinostat, or Panobinostat, or is a nonhydroxamic acid-based HDAC inhibitor such as the 2-aminophenylamides MS-27510 or MGCD-010311 or the dithiol FK22812. In other embodiments, the HDAC inhibitors are 5-(trifluoroacetylj- thiophene-2-carboxamides, which are potent and selective class II HDAC inhibitors, or a pharmaceutically acceptable salt or composition thereof, in combination with one or more of finasteride, minoxidil, dutasteride, spironolactone, latanoprost, or oral contraceptives.
Defective decidualization of endometrial stromal cells (ESCs) in endometriosis (EM) patients leads to inadequate endometrial receptivity and EM-associated infertility. Hypoxia is an inevitable pathological process of EM and participates in deficient decidualization of the eutopic secretory endometrium. Enhancer of zeste homology 2 (EZH2) is a methyltransferase which catalyses H3K27Me3, leading to decreased expression levels of target genes. Although EZH2 expression is low under normal decidualization, it is abundantly increased in the eutopic secretory endometrium of EM and is induced by hypoxia. Chromatin immunoprecipitation-PCR results revealed that decidua marker IGFBP1 is a direct target of EZH2, partially explaining the increased levels of histone methylation modification in defected decidualization of EM. To mechanism controlling this, we examined the effects of hypoxia on EZH2 and decidualization. EZH2 mRNA showed decreased m6 A modification and increased expression levels under hypoxia and decidualization combined treatment. Increased EZH2 expression was due to the increased expression of m6 A demethylase ALKBH5 and decreased expression of the m6 A reader protein YTHDF2. YTHDF2 directly bind to the m6 A modification site of EZH2 to promote EZH2 mRNA degradation in ESCs. Moreover, selective Ezh2 depletion in mouse ESCs increased endometrial receptivity and improved mouse fertility by up-regulating decidua marker IGFBP1 expression. This is the first report showing that YTHDF2 can act as a m6 A reader to promote decidualization by decreasing the stability of EZH2 mRNA and further increasing the expression of IGFBP1 in ESCs. Taken together, our findings highlight the critical role of EZH2/H3K27Me3 in decidualization and reveal a novel epigenetic mechanism by which hypoxia can suppress EM decidualization by decreasing the m6 A modification of EZH2 mRNA.
Exercises including mirror therapy will be applied to the participants in the Mirror Therapy group. The mirror will be placed in such a way that the affected extremity of the patient could not be seen behind the mirror and the healthy extremity would be in front of his eyes, the patient will perform the exercises indicated by the physiotherapist with his intact extremity, looking into the mirror. The exercises will be performed in sessions lasting 60 minutes, 3 days a week, over 8 weeks.
BACKGROUND: This systematic review and network meta-analysis aimed to assess the comparative effectiveness and safety profiles of current combination therapies based on androgen deprivation therapy (ADT) for the heterogeneous population of individuals with metastatic castration-sensitive prostate cancer (mCSPC).
METHODS: We retrieved pertinent literature from PubMed, EMBASE, the Cochrane Library, ClinicalTrials.gov, and international conference databases. The study was registered in the Prospective Register of Systematic Reviews (CRD42023453853) for transparency.
RESULTS: Our analysis included 20 RCTs involving 14,995 patients, evaluating 15 ADT-based combinations, including systemic therapies, radiotherapy and surgery. In the overall population, the darolutamide triplet (DARO + docetaxel + ADT) demonstrated comparable overall survival (OS) benefits to prostatectomy/radical local therapy (RLT) plus ADT (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.43-1.57). Additionally, the enzalutamide (ENZ) triplet (ENZ + DOC + ADT) appeared to confer the best progression-free survival (HR, 0.34; 95% CI: 0.27-0.43). Subgroup analysis based on metastatic burden indicated that RLT plus ADT had the best OS performance in patients with low burden, while the DARO triplet was associated with the best OS in patients with high burden. Regarding adverse events (AEs), the addition of certain androgen receptor pathway inhibitor (ARPI) agents to ADT led to an increased incidence of severe AEs, while the addition of DOC to the ARPI doublet did not appear to elevate the exposure-adjusted incidence rates.
CONCLUSIONS: Our findings suggest that combined treatments result in better survival outcomes than does ADT alone. In the current landscape of systemic therapy, the significance of local therapy should not be underestimated, and therapeutic decisions should be tailored with meticulous consideration of clinical heterogeneity among patients.
Non-irritant skin-cleanin compsn. which does not require rinsing and which removes soil both on the surface and in the pores comprises only those ingredients which are known to be compatible with the skin and is applied simply by smearing over the skin. Essential components are (1) a cpd. which forms an adhesive filmogenic gel with water e.g. PVA; (2) a solvent esp. water and (3) a water sol. detergent.
Noisy tinnitus is a common auditory system disease characterized by persistent tinnitus symptoms. The TLR4/NF - κ B/NLRP3 signaling pathway plays an important role in neuroinflammatory response. Select 6 control and 6 noise exposed mice for transcriptome sequencing analysis in the hippocampus, conduct high-throughput data analysis, identify differentially expressed genes, and screen for pathways. Auditory brainstem response (ABR) detection was performed to understand the hearing changes, and the modeling effect was evaluated using the GPIAS% inhibition experiment of auditory startle reflex. Morphological observation of the basement membrane was performed to determine whether the inner hair cells were damaged. Immunohistochemistry and immunofluorescence were used to determine the activation of microglia in the hippocampus of noise induced tinnitus mice. Finally, qPCR and Western Blot were used to detect the expression of TLR4, NF kB, NLRP3, caspase-1, and IL-1 β in the hippocampus of each group of mice. Through high-throughput data analysis, it was found that there was no significant difference in the auditory threshold of the three groups of mice; After 2 h of exposure to 100 dB SPL noise, the GPIAS% of mice decreased significantly compared to before exposure, and membrane construction was successful. After 7 days, the GPIAS% of the drug intervention group increased. After noise exposure, mice developed tinnitus, and hippocampus neuroinflammation. Roflupram can inhibit neuroinflammation and improve tinnitus through the TLR4/NF kB/NLRP3/caspase-1/IL-1 β signaling pathway.
The invention relates to the treatment and diagnosis of cancer and to the development of drugs. The invention provides a catalogue of >350 targets of the myc oncogene family. The invention provides the insight that it is the myc oncogene family itself that provides for the recruitment and adaptation of the in essence normal physiological mechanisms and events to support the essentially neoplastic character of a cancer cell. Herewith the invention provides a method for the treatment of cancer comprising modulating a myc-dependent downstream gene. The invention also provides a method to use one or more gene products of myc-downstream genes as readout in screenings assays to identify drugs. The insight provided by the invention that myc boosts the cellular protein synthesis machinery can be used to optimise cellular production systems for recombinant protein synthesis systems.
PURPOSE: Assessing fluency in aphasia is diagnostically important for determining aphasia type and severity and therapeutically important for determining appropriate treatment targets. However, wide variability in the measures and criteria used to assess fluency, as revealed by a recent survey of clinicians (Gordon & Clough, 2022), results in poor reliability. Furthermore, poor specificity in many fluency measures makes it difficult to identify the underlying impairments. Here, we introduce the Flu-ID Aphasia, an evidence-based tool that provides a more informative method of assessing fluency by capturing the range of behaviors that can affect the flow of speech in aphasia.
METHOD: The development of the Flu-ID was based on prior evidence about factors underlying fluency (Clough & Gordon, 2020; Gordon & Clough, 2020) and clinical perceptions about the measurement of fluency (Gordon & Clough, 2022). Clinical utility is maximized by automated counting of fluency behaviors in an Excel template. Reliability is maximized by outlining thorough guidelines for transcription and coding. Eighteen narrative samples representing a range of fluency were coded independently by the authors to examine the Flu-ID's utility, reliability, and validity.
RESULTS: Overall reliability was very good, with point-to-point agreement of 86% between coders. Ten of the 12 dimensions showed good to excellent reliability. Validity analyses indicated that Flu-ID scores were similar to clinician ratings on some dimensions, but differed on others. Possible reasons and implications of the discrepancies are discussed, along with opportunities for improvement.
CONCLUSIONS: The Flu-ID assesses fluency in aphasia using a consistent and comprehensive set of measures and semi-automated procedures to generate individual fluency profiles. The profiles generated in the current study illustrate how similar ratings of fluency can arise from different underlying impairments. Supplemental materials include an analysis template, extensive guidelines for transcription and coding, a completed sample, and a quick reference guide.
SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.27078199.
The objective of this prospective multicenter cohort study of patients undergoing surgery for glenohumeral instability is to identify the outcomes, and more importantly, the previously unknown predictors of sports function, activity level, general health, recurrent instability symptoms, and surgical failures following surgery. Patient information at the time of the surgery (demographics, validated outcome measures), in addition to the physical exam findings, shoulder pathology at the time of surgery, and surgical treatment will be obtained. The validated outcome instruments are American Shoulder and Elbow Surgeons Score, Western Ontario Shoulder Instability, Kerlan Jobe Overhand Athlete Score, Shoulder Activity Score, and RAND-36. Post-operative physical exam data will be obtained at 6 months after surgery. Patient reported outcomes will be repeated at 2, 6, 10, and 20 years post-operatively. Our multivariable analysis will identify which of the many factors related to the injury, intra-operative treatment, postoperative care, physical patient characteristics, and behavioral patient characteristics contribute to recurrence and poor outcome.
The time course of socio-communicative disturbances in children after posterior fossa tumor resection is variable in clinical reports, and its assessment may help to understand the role of the cerebellum in the pathogenesis of socio-communicative disorders and improve rehabilitation plans. We report the 3-year cognitive-behavioral follow-up of a female patient (LZ) who underwent surgical ablation of the vermis due to medulloblastoma at age 9. LZ developed a severe post-operative Cerebellar Cognitive Affective Syndrome (CCAS) with cognitive-executive dysfunctions and behavioral alterations resembling an Autism Spectrum Disorder (ASD)-like syndrome. The lack of empathy and reduced ability to recognize others' intentions and mental states persisted at follow-up evaluations, as did language alterations. The present case report evidenced that lesions affecting cerebellar and vermal lobules may cause severe CCAS and impairment of social skills overlapping with that observed in ASD. This case is significant in its clinical features, revealing long-term social impairment, while the cognitive, linguistic, and executive functioning improved over time. Prospective case studies should plan the evaluation of symptoms of ASD within the clinical longitudinal assessment.
PURPOSE OF REVIEW: This review describes pathologic conditions of retrograde flow into the esophagus along with recent therapeutic advances and treatment options.
RECENT FINDINGS: The esophagus facilitates anterograde and retrograde movement of contents, the latter of which is mediated by transient lower esophageal sphincter relaxations (TLESRs). Gastroesophageal reflux disease (GERD) often includes esophageal-specific symptoms such as heartburn or regurgitation. Volume regurgitation responds less frequently to acid suppression with proton pump inhibitors (PPIs) than heartburn, given its relationship with incompetence of the esophagogastric junction (EGJ) and increased frequency of TLESRs. Therefore, although the refluxate pH can be altered with PPIs, the frequency of reflux episodes is generally not reduced and surgical and endoscopic treatments may be favored. Other instances of abnormal retrograde esophageal flow respond better to medical therapy, or lifestyle interventions. Compared to gastric belching because of increased stomach distension, supragastric belching is caused by intake of air from pharynx into the esophagus followed by rapid expulsion of air. These conditions can be distinguished on esophageal tests such as high-resolution manometry and are likely to respond to behavioral modifications.
SUMMARY: Retrograde flow into the esophagus can be a normal occurrence, but diagnostic testing to distinguish causes can guide appropriate intervention.
OBJECTIVE: Previous studies of alcohol consumption during pregnancy and omphalocele have produced mixed results. We updated an earlier analysis of National Birth Defects Prevention Study (NBDPS) data, adding six years of participants, to examine associations between maternal alcohol consumption and omphalocele.
METHODS: NBDPS was a multi-site, population-based case-control study in the United States. Cases were identified from birth defect surveillance programs in 10 states; controls were liveborn infants without a birth defect randomly selected from the same catchment areas. Mothers self-reported alcohol consumption during the periconceptional period (one month before through the third gestational month) via telephone interview. Our study included mothers of 410 omphalocele cases and 11,219 controls with estimated dates of delivery (EDDs) during 1997-2011. We used logistic regression to estimate adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for periconceptional alcohol consumption and omphalocele. We performed a probabilistic bias analysis to evaluate the impact of alcohol exposure misclassification on our results.
RESULTS: Overall, 44% of case and 38% of control mothers reported periconceptional alcohol consumption; 22% and 17%, respectively, reported binge drinking. Any maternal periconceptional alcohol consumption was associated with modestly increased odds of omphalocele (AOR 1.35, 95% CI 1.09, 1.68), as was binge drinking (AOR 1.47, 95% CI 1.08, 2.01). Our bias analysis yielded estimates further from the null.
CONCLUSIONS: We observed modest associations between maternal periconceptional alcohol consumption and omphalocele. Based on our bias analysis, studies of alcohol and birth defects not accounting for exposure misclassification may underestimate associations.
The application belongs to the technical field of biology, and particularly relates to a preparation method and application of a cell ball. The application provides a preparation method of a cell ball, which comprises the following steps: in a magnetic environment, performing mixed culture on the magnetic micropore array, the suspended cells and the culture medium in a culture dish, removing the magnetic environment, and then performing centrifugal treatment to prepare cell spheres; and micro blind holes are formed in the surface of the magnetic micropore array. The method captures the suspended cells in the three-dimensional space of the culture medium by using the magnetic force to pull the magnetic micropore arrays, and has the advantage of high space utilization rate. Thus, the yield of cell pellets from a single multi-well culture dish is higher for the methods of the present application. Meanwhile, the prepared hepatocyte cell balls can effectively increase the survival rate of mice with acute liver failure and promote the repair of damaged liver tissues. Therefore, the application provides a preparation method and application of the cell spheres, which are used for solving the technical defects that the cell spheres prepared by the prior art are often different in size or difficult to prepare on a large scale.