anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Biallelic variants in the ERLIN1 gene were recently reported as the cause of two motor neuron degeneration diseases, SPG62 and a recessive form of amyotrophic lateral sclerosis. However, only 12 individuals from five pedigrees have been identified so far. Thus, the description of the disease remains limited. Following the discovery of a homozygous pathogenic variant in a girl with SPG62, presenting with intellectual disability, and epilepsy, we gathered the largest series of SPG62 cases reported so far (13 individuals) to better understand the phenotype associated with ERLIN1. We collected molecular and clinical data for 13 individuals from six families with ERLIN1 biallelic variants. We performed RNA-seq analyses to characterize intronic variants and used Alphafold and a transcripts database to characterize the molecular consequences of the variants. We identified three new variants suspected to alter the bell-shaped ring formed by the ERLIN1/ERLIN2 complex. Affected individuals had childhood-onset paraparesis with slow progression. Six individuals presented with gait ataxia and three had superficial sensory loss. Aside from our proband, none had intellectual disability or epilepsy. Biallelic pathogenic ERLIN1 variants induce a rare, predominantly pure, spastic paraparesis, with possible cerebellar and peripheral nerve involvement.
Intervention Arm (ATP): All ATP assessments at 6 monthly intervals post baseline will be conducted by an ATP trained clinician. This interview will be video recorded.The ATP clinicians will then fill out a standardized medical template that will be reviewed by a psychiatrist who will provide a written assessment and psychiatric treatment plan. He will have access to any previous assessments and the PCP will also have continuing access to this psychiatrist by phone or email between the 3 consultations.
The invention provides a polypeptide, the amino acid sequence of which is shown as SEQ ID NO. 1. The invention also provides a DNA molecule for encoding the polypeptide. The invention also provides a recombinant vector which contains the DNA molecule. The invention also provides application of the polypeptide in preparing a medicament for treating myocardial fibrosis. Compared with the existing polypeptide for treating myocardial fibrosis, the polypeptide is secreted in a large amount under the physiological condition after exercise, so that the polypeptide has no obvious adverse reaction to organisms, can relieve myocardial fibrosis by increasing exercise amount in normal organisms and organisms in early disease, and can relieve myocardial fibrosis by in vitro administration of the polypeptide in middle and later stages, especially under the condition of exercise limitation. Therefore, the invention can inhibit the transformation from cardiac fibroblasts to myofibroblasts and relieve myocardial fibrosis.
Ulcerative colitis (UC) is a subtype of inflammatory bowel disease affecting the colon with idiopathic origin. Melinjo endosperm extract (MeE) contains polyphenolic compounds that have antioxidative and anticancer properties. We examined the effect of MeE on inflammation and mucin expression in the colons of UC of mice treated with dextran sulfate sodium (DSS). C57BL/6J male mice were assigned into four categories: control, DSS + 0% MeE, DSS + 0.1% MeE, and DSS + 0.5% MeE. The control group was provided distilled water and a standard chow diet for 4 weeks. In DSS + 0% MeE, DSS + 0.1% MeE, and DSS + 0.5% MeE groups, the mice were treated with MeE for 3 weeks followed by MeE diets and drinking water containing 3% DSS for a week. Macrophage count, the mucus area stained by Alcian blue (AB), the levels of adenosine monophosphate-activated protein kinase (AMPK), nuclear factor-κB (NFκB) p65, and silent information regulator (Sirt) 1 protein expression, as well as proinflammatory mediators and Mucin 2 mRNA expression were assessed. In the DSS + 0% MeE group, the AB-stained areas and Mucin 2 mRNA expression levels were observed to be lower than those of controls. However, the levels in the +0.5% MeE group were significantly increased. Compared with the control group, the macrophage number, the expression of IL-1β mRNA, and NFκB p65 protein in the DSS + 0% MeE group showed a significant increase. Conversely, these levels were significantly decreased in the +0.5% MeE group. The phosphorylated AMPK and Sirt1 protein levels were upregulated in the +0.5% MeE group. In conclusion, MeE may alleviate UC injury by reducing macrophage infiltration and regulating the AMPK/NFκB/Sirt1 pathway.
BACKGROUND: Hypertensive disorders of pregnancy (HDP) are associated with subsequent adverse cardiac remodeling and cardiovascular disease. The role of myocardial microvascular disease among individuals with HDP and left ventricular (LV) remodeling as a potential link to cardiovascular disease is unknown. We aimed to determine whether individuals with HDP history have coronary microvascular dysfunction measured by coronary flow reserve 8 to 10 years after delivery and whether microvascular dysfunction correlates with LV remodeling.
METHODS: Individuals with pregnancies delivered from 2008 to 2010 underwent burst-replenishment myocardial contrast echocardiography (2017-2020) to quantify myocardial perfusion at rest and during dobutamine stress. Video intensity versus time data were used to derive β, the rate of rise of video intensity, a correlate for myocardial blood flow. Coronary flow reserve was calculated as the ratio of β at peak stress to β at rest, averaged across LV myocardial regions of interest.
RESULTS: We studied 91 individuals (aged 38±6 and 9.1±0.9 years postdelivery) and 19 with a history of HDP. Individuals with coronary microvascular dysfunction (coronary flow reserve <2.0; n=13) had a higher proportion of HDP (46.2% versus 16.7%; P=0.026) and higher prepregnancy body mass index, baseline heart rate, and hemoglobin A1c compared with those without microvascular dysfunction. The association of coronary flow reserve and HDP was attenuated after adjusting for cardiometabolic factors (P=0.133). In exploratory subgroup analyses, individuals with both LV remodeling (relative wall thickness >0.42) and HDP (n=12) had the highest proportion of microvascular dysfunction (41.7% versus +HDP-LV remodeling [n=7] 14.3%; -HDP+LV remodeling [n=26] 7.7%; P=0.0498).
CONCLUSIONS: In this small study, HDP history is associated with coronary microvascular dysfunction 1 decade after delivery, findings that may, in part, be driven by metabolic factors including obesity and diabetes. Microvascular dysfunction may contribute to cardiovascular disease among individuals with a history of HDP.
Four subjects inadvertently received felbamate as adjunctive therapy in dosages ranging from 5,400 to 7,200 mg/day for durations between 6 and 51 days. One subject who received 5,400 mg/day as monotherapy for 1 week reported no adverse experiences. Another subject attempted suicide by ingesting 12,000 mg of felbamate in a 12-hour period. The only adverse experiences reported were mild gastric distress and a resting heart rate of 100 bpm. No serious adverse reactions have been reported. General supportive measures should be employed if overdosage occurs. It is not known if felbamate is dialyzable.
BACKGROUND/OBJECTIVE: Meningioma calcification is thought to predict reduced growth potential and aggression. However, historical studies have primarily focused on correlating calcification in small meningiomas (diameter less than 2.5 cm) rather than analyzing characteristics of calcified meningiomas across all sizes. In this study, we investigate the pathologic and clinical implications of meningioma calcification.
METHODS: We utilized a historical database of 342 consecutive newly diagnosed intracranial meningiomas with preoperative computed tomography and magnetic resonance imaging scans treated at a single institution from 2005 to 2019. We correlated the presence of calcification with patient demographics, grade, Mindbomb Homolog-1 index, location, volume, Simpson grade, and recurrence using both univariate and multivariate generalized linear models.
RESULTS: On univariate analysis, no single variable correlated with tumor calcification. Notably, neither tumor 2021 World Health Organization grade (P = 0.91) nor Mindbomb Homolog-1 index (P = 0.62) predicted calcification. After accounting for demographic characteristics and tumor volume and location, there was no significant association between 2021 World Health Organization grade (P = 0.52) and Mindbomb Homolog-1 index (P = 0.54) and calcification. Calcification had no influence on resection grade (P = 0.59) or recurrence (P = 0.80).
CONCLUSIONS: In this series, calcified meningiomas exhibited similar 2021 World Health Organization tumor grading distribution, proliferation indexes, and immediate surgical outcomes compared to their noncalcified counterparts. These findings question the historical role of using meningioma calcification as an independent guide to their management.
Cancer is a multifactorial pathological condition characterized by uncontrolled cellular proliferation, genomic instability, and evasion of regulatory mechanisms. It arises from the accumulation of genetic mutations confer selective growth advantages, leading to malignant transformation and tumor formation. The intricate interplay between LncRNAs and the Hedgehog pathway has emerged as a captivating frontier in cancer research. The Hedgehog pathway, known for its fundamental roles in embryonic development and tissue homeostasis, is frequently dysregulated in various cancers, contributing to aberrant cellular proliferation, survival, and differentiation. The Hh pathway is crucial in organizing growth and maturation processes in multicellular organisms. It plays a pivotal role in the initiation of tumors as well as in conferring resistance to conventional therapeutic approaches. The crosstalk among the Hh pathway and lncRNAs affects the expression of Hh signaling components through various transcriptional and post-transcriptional processes. Numerous pathogenic processes, including both non-malignant and malignant illnesses, have been identified to be induced by this interaction. The dysregulation of lncRNAs has been associated with the activation or inhibition of the Hh pathway, making it a potential therapeutic target against tumorigenesis. Insights into the functional significance of LncRNAs in Hedgehog pathway modulation provide promising avenues for diagnostic and therapeutic interventions. The dysregulation of LncRNAs in various cancer types underscores their potential as biomarkers for early detection and prognostication. Additionally, targeting LncRNAs associated with the Hedgehog pathway presents an innovative strategy for developing precision therapeutics to restore pathway homeostasis and impede cancer progression. This review aims to elucidate the complex regulatory network orchestrated by LncRNAs, unravelling their pivotal roles in modulating the Hedgehog pathway and influencing cancer progression.
Solar UVB irradiation cause skin photoaging by inducing the high expression of matrix metalloproteinase (MMPs) to inhibit the expression of Type1 procollagen synthesis. 1-Kestose, a natural trisaccharide, has been indicated to show a cytoprotective role in UVB radiation-induced-HaCaT cells. However, few studies have confirmed the anti-aging effects. In the present study, we evaluated the anti-photoaging and pathological mechanism of 1-kestose using Human keratinocytes (HaCaT) cells. The results found that 1-kestose pretreatment remarkably reduced UVB-generated reactive oxygen species (ROS) accumulation in HaCaT cells. 1-Kestose suppressed UVB radiation-induced MMPs expressions by blocking MAPK/AP-1 and NF-κB p65 translocation. 1-Kestose pretreatment increased Type 1 procollagen gene expression levels by activating TGF-β/Smad signaling pathway. Taken together, our results demonstrate that 1-kestose may serve as a potent natural trisaccharide for inflammation and photoaging prevention.
PURPOSE: As a vital component of the hepatitis B virus (HBV) nucleocapsid, HBV core protein (HBC) contributes to hepatocarcinogenesis. Here, we aimed to assess the effects of RANGAP1 and KDM2A on tumorigenesis induced by HBC.
METHODS: Co-immunoprecipitation (Co-IP) combined with mass spectrometry were utilized to identify the proteins with the capacity to interact with HBC. The gene and protein levels of RANGAP1 and KDM2A in hepatocellular carcinoma (HCC) and HBV-positive HCC tissues were evaluated using different cohorts. The roles of RANGAP1 and KDM2A in HCC cells mediated by HBC were investigated in vitro and in vivo. Co-IP and western blot were used to estimate the interaction of HBC with RANGAP1 and KDM2A and assess RANGAP1 stabilization regulated by HBC.
RESULTS: We discovered that HBC could interact with RANGAP1 and KDM2A, the levels of which were markedly elevated in HCC tissues. Relying on RANGAP1 and KDM2A, HBC facilitated HCC cell growth and migration. The increased stabilization of RANGAP1 mediated by HBC was relevant to the disruption of the interaction between RANGAP1 and an E3 ligase SYVN1. RANGAP1 interacted with KDM2A, and it further promoted KDM2A stabilization by disturbing the interaction between KDM2A and SYVN1. HBC enhanced the interaction of KDM2A with RANGAP1 and upregulated the expression of KDM2A via RANGAP1 in HCC cells.
CONCLUSIONS: These findings demonstrate a novel mechanism by which HBC facilitates hepatocarcinogenesis. RANGAP1 and KDM2A could act as potential molecular targets for treating HBV-associated malignancy.
The present invention teaches the use of antibodies raised against the Group A mucopeptide for the treatment of septic shock and Rheumatoid Arthritis, and the identification of specific peptides that can be used in such treatments. The invention includes methods of using the antibodies raised against the Group A mucopeptide including as a means identifying specific peptides, the specificpeptides themselves, and methods of using the peptides. In certain embodiments, the specific peptides serve as mimics to these antibodies. Such peptides can be administered to an animal subject to block the microbial action that initiates Rheumatoid Arthritis via tumor necrosis factor. Alternatively, specific peptides of the present invention can be used to immunize Rheumatoid Arthritis-susceptible individuals to prevent further progression of the diseases. In still other embodiments, the peptides serve as binding partners for these antibodies.
PROBLEM TO BE SOLVED: To provide methods of enhancing the engraftment procedure of hematopoietic stem and progenitor cells (HSPC).SOLUTION: A composition contains a population of hematopoietic stem and/or progenitor cells, a compound having PGEactivity, and a viral vector. A compound having PGEactivity is selected from the group consisting of an E series prostaglandin, and dimethyl-derivatives of E series prostaglandins. The compound having PGEactivity is selected from the group consisting of PGEand 16,16-dimethyl PGE2. A source of cells is cord blood, bone marrow, or mobilized peripheral blood. The hematopoietic stem and/or progenitor cells are CD34+. The composition comprises a population of hematopoietic stem and/or progenitor cells treated ex vivo with a compound having an effective amount of PGE2 activity and transfected with a viral vector containing at least one gene of interest for transduction.SELECTED DRAWING: None
DOMS was induced for the trunk muscles with a load equals to 80% of the maximum repetitive voluntary contraction. Pulmonary function parameters, respiratory muscle strength and endurance, exercise capacity, pain, fatigue, and dyspnea perception severity were recorded before DOMS and at the 24th and 48th hours after DOMS.
EVs are being recognized as vectors for drug delivery. In particular, EV loading with targeting and therapeutic agents brings along an interesting opportunity to translate EVs into a bio-mimetic selective delivery system. Indeed, EVs constitute a physiological carrier being potentially less immunogenic than artificial delivery vehicles. The inventors now developed a novel method to control the loading of a cargo into EVs on demand. These EVs are equipped, if necessary, with non-viral fusogen, therefore enhancing EV-cargo delivery into acceptor cells. To acutely measure this process, they follow the fate of a luciferase-tagged cargo. Cargo loading was enabled through a drug-reversible inducible dimerization system. Briefly, donor cells were transfected with plasmids encoding for FKBP-tagged CD63, a classical membrane EV marker, and FRB-Nanoluciferase (NLuc) that is normally cytosolic. Upon addition of the dimerizing drug, FRB-Nluc interacts with FKBP-CD63 and is recruited into secreted EVs. This is accompanied by an enhanced delivery into acceptor cells. This phenomenon can be further enhanced when EVs are equipped with syncitin1, a mammalian fusogenic protein that trigger fusion between EV membrane and the plasma membrane of acceptor cells. Using this novel process, the inventors further demonstrated that the catalytic domain of the Diphteria toxin (DTA), that is responsible for protein synthesis inhibition and ultimately cell death, can be delivered to acceptor cells via functionalized EVs. This led to protein synthesis inhibition and death of acceptor cells. This novel method and the derived applications promise to open new doors in precision care medicine, especially when EVs will be equipped with antibodies raised against cell specific antigens.
Compositions and methods of making cells using RNA, and cells made using the disclosed compositions and methods are also provided. In exemplary embodiments, RNA is transfected into cells to effect a molecular, biological, physiological, or histological change in the cells. In preferred embodiments, the RNA is prepared in vitro, more preferably using a DNA template according to the provided compositions and methods. Methods for treating or inhibiting a disorder or disease such cancer are also provided. The methods can include, for example, locally or systemically administering to the host an effective amount of one or more RNAs; or an effective amount of population of cells isolated from the subject or a syngeneic or histocompatible subject, contacted ex vivo with one or RNAs, and optionally expanded. The cells can be, for example, immune cells or stem cells.
Tetrabenazine elevates serum prolactin concentrations in humans. Following administration of 25 mg to healthy volunteers, peak plasma prolactin levels increased 4- to 5-fold. Tissue culture experiments indicate that approximately one third of human breast cancers are prolactin-dependent in vitro, a factor of potential importance if tetrabenazine tablets are being considered for a patient with previously detected breast cancer. Although amenorrhea, galactorrhea, gynecomastia, and impotence can be caused by elevated serum prolactin concentrations, the clinical significance of elevated serum prolactin concentrations for most patients is unknown. Chronic increase in serum prolactin levels (although not evaluated in the tetrabenazine development program) has been associated with low levels of estrogen and increased risk of osteoporosis. If there is a clinical suspicion of symptomatic hyperprolactinemia, appropriate laboratory testing should be done and consideration should be given to discontinuation of tetrabenazine tablets.
Objective: Music listening intervention has made great strides in improving the condition of stroke survivors. Thus, this research explores the effects of music listening intervention on post-stroke survivors during rehabilitation by using P. Ramlee songs.

Materials \& Methods: In the first phase, surveys were conducted to determine the selection of songs to be used in the second phase. The second phase is applying music listening intervention on a small sample of 20 subjects, aged 55 years old and above. The participants were categorized into two groups: stroke survivors and healthy individuals and randomized into control group (without music) and experimental group (with music). The second phase consists of three stages. Stage one is to pre-screen and select potential subjects before the experiment. The second stage aims to determine the effect of P. Ramlee music on stroke survivors during their rehabilitation through augmenting their brain neuroplasticity with measurement of the MEP using TMS. The final stage compares the effects of MEP between lesion and non-lesion areas.
Selection experiments play an increasingly important role in comparative and evolutionary physiology. However, selection experiments can be limited by relatively low statistical power, in part because replicate line is the experimental unit for analyses of direct or correlated responses (rather than number of individuals measured). One way to increase the ability to detect correlated responses is through a meta-analysis of studies for a given trait across multiple generations. To demonstrate this, we applied meta-analytic techniques to two traits (body mass and heart ventricle mass, with body mass as a covariate) from a long-term artificial selection experiment for high voluntary wheel-running behavior. In this experiment, all four replicate High Runner (HR) lines reached apparent selection limits around generations 17-27, running approximately 2.5- to 3-fold more revolutions per day than the four non-selected Control (C) lines. Although both traits would also be expected to change in HR lines (relative heart size expected to increase, expected direction for body mass is less clear), their statistical significance has varied, despite repeated measurements. We compiled information from 33 unique studies and calculated a measure of effect size (Pearson's R). Our results indicate that, despite a lack of statistical significance in most generations, HR mice have evolved larger hearts and smaller bodies relative to controls. Moreover, plateaus in effect sizes for both traits coincide with the generational range during which the selection limit for wheel-running behavior was reached. Finally, since reaching the selection limit, absolute effect sizes for body mass and heart ventricle mass have become smaller (i.e. closer to 0).
Postictal children aged one to 18 years who presented to the pediatric emergency department underwent head CT according to the Pediatric Emergency Care Applied Research Network (PECARN) guidelines. The seizures were observed by a health worker or directly with home videos.
Patients receive 1 cycle (28 days) of endocrine therapy consisting of goserelin acetate SC on day 1 and letrozole or anastrozole PO QD. Neoadjuvant treatment repeats every 28 days for a total of 16-18 weeks in the absence of disease progression or unacceptable toxicity. Patients then undergo the appropriate standard surgical procedure to remove the cancer. Recommendations for postsurgical treatment will be based on PEPI score and physician discretion.
Subjects will begin with receiving infliximab at 5 mg/kg for the first visits. If there is no response to treatment, or flare at any visit (beginning at visit #3), infliximab dose or dosing frequency will be increased in a gradual fashion, up to a maximum of 15 mg/kg every 6 weeks, until response is achieved.