anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
BACKGROUND: The parent-proxy paediatric chronic cough quality of life questionnaire (PC-QoL) is a commonly used measure of spillover quality of life in parents of children with chronic cough. To date, spillover health utility in these parents is not routinely estimated largely due to the lack of a suitable instrument. Their perspective is not included in economic evaluations of interventions for their children. We explored developing a health state classification system based on the PC-QoL for measuring health utility spill over in this population.
METHODS: This study included PC-QoL 8-item responses of 653 parents participating in a prospective cohort study about paediatric chronic cough. Exploratory factor analysis (EFA) and Rasch analysis were used to examine dimensionality and select potential items and level structure.
RESULTS: EFA indicated that the PC-QoL had one underlying domain. Rasch analysis indicated threshold disordering in all items which improved when items were collapsed from seven to four levels. Two demonstrated differential item functioning (DIF) by diagnosis or ethnicity and were excluded from the final scale. This scale satisfied Rasch assumptions of local independence and unidimensionality and demonstrated acceptable fit to the Rasch model. It was presented to and modified by an expert panel and a consumer panel. The resulting classification system had six items, each with four levels.
DISCUSSION: The PC-QoL can conform to a Rasch model with minor modifications. It may be a good basis for the classification system of a child cough-specific PBM. A valuation study is required to estimate preference weights for each item and to estimate health utility in parents of children with chronic cough.
PURPOSE OF REVIEW: The aim of this review is to outline recent studies relating to nutritional status and outcomes in pediatric end-stage liver disease.
MAIN FINDINGS: Pediatric patients with chronic and end-stage liver disease are at high risk of malnutrition. Given additional growth demands in children and the inherent complications of chronic liver disease, achieving adequate nutrition in these patients remains a challenge. In addition, while guidelines on nutrition in chronic liver disease exist, global approaches and definitions of malnutrition vary. Recent literature has focused on sarcopenia and nutrition-related transplant outcomes, with some studies exploring nutritional assessment and management. Pediatric studies however continue to lag adult research, with limited prospective and interventional studies.
SUMMARY: Optimizing nutrition in pediatric end-stage liver disease remains a challenge, however understanding of the mechanisms and clinical manifestations of malnutrition in this population is improving. Despite these efforts, high quality studies to determine optimal nutrition strategies and interventions are lacking behind adult evidence and should be the focus of future research.
Clinical trials of mesalamine did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently from younger patients. Reports from uncontrolled clinical studies and postmarketing reporting systems suggested a higher incidence of blood dyscrasias (i.e., agranulocytosis, neutropenia, and pancytopenia) in patients who were 65 years or older who were taking mesalamine-containing products such as mesalamine delayed-release tablets compared to younger patients. Monitor complete blood cell counts and platelet counts in elderly patients during treatment with mesalamine.

Systemic exposures are increased in elderly subjects [see Clinical Pharmacology (12.3)]. 

In general, consider the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy in elderly patients when prescribing mesalamine. Consider starting at the low end of the dosing range for induction in elderly patients [see Dosage and Administration (2), Use in Specific Populations (8.6)].
AIMS/HYPOTHESIS: While the association between coeliac disease and type 1 diabetes is well documented, the association of coeliac disease with type 2 diabetes risk remains undetermined. We conducted a nationwide cohort and Mendelian randomisation analysis to investigate this link.
METHODS: This nationwide matched cohort used data from the Swedish ESPRESSO cohort including 46,150 individuals with coeliac disease and 219,763 matched individuals in the comparator group selected from the general population, followed up from 1969 to 2021. Data from 9053 individuals with coeliac disease who underwent a second biopsy were used to examine the association between persistent villous atrophy and type 2 diabetes. Multivariable Cox regression was employed to estimate the associations. In Mendelian randomisation analysis, 37 independent genetic variants associated with clinically diagnosed coeliac disease at p<5×10-8 were used to proxy genetic liability to coeliac disease. Summary-level data for type 2 diabetes were obtained from the DIAGRAM consortium (80,154 cases) and the FinnGen study (42,593 cases).
RESULTS: Over a median 15.7 years' follow-up, there were 6132 (13.3%) and 30,138 (13.7%) incident cases of type 2 diabetes in people with coeliac disease and comparator individuals, respectively. Those with coeliac disease were not at increased risk of incident type 2 diabetes with an HR of 1.00 (95% CI 0.97, 1.03) compared with comparator individuals. Persistent villous atrophy was not associated with an increased risk of type 2 diabetes compared with mucosal healing among participants with coeliac disease (HR 1.02, 95% CI 0.90, 1.16). Genetic liability to coeliac disease was not associated with type 2 diabetes in DIAGRAM (OR 1.01, 95% CI 0.99, 1.03) or in FinnGen (OR 1.01, 95% CI 0.99-1.04).
CONCLUSIONS/INTERPRETATION: Coeliac disease was not associated with type 2 diabetes risk.
Risk Summary

Linaclotide and its active metabolite were not detected in the milk of lactating women (see Data). In adults, concentrations of linaclotide and its active metabolite were below the limit of quantitation in plasma following multiple doses of LINZESS [see Clinical Pharmacology (12.3)]. Maternal use of LINZESS is not expected to result in exposure to linaclotide or its active metabolite in breastfed infants. There is no information on the effects of linaclotide or its active metabolite on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for LINZESS and any potential adverse effects on the breastfed infant from LINZESS or from the underlying maternal condition. 

Data

Following oral administration of 72 mcg, 145 mcg, or 290 mcg of LINZESS once daily for 3 days to breastfeeding mothers taking linaclotide therapeutically, the concentrations of linaclotide and its metabolite were below the limits of quantitation (<0.25 ng/mL and <1 ng/mL, respectively) in all breast milk samples collected over 24 hours.
BACKGROUND: Pulmonary arterial hypertension (PAH) is characterized by excessive proliferation of small pulmonary arterial vascular smooth muscle cells (PASMCs), endothelial dysfunction, and extracellular matrix remodeling. G protein-coupled receptor kinase 2 (GRK2) plays an important role in the maintenance of vascular tone and blood flow. However, the role of GRK2 in the pathogenesis of PAH is unknown.
METHODS: GRK2 levels were detected in lung tissues from healthy people and PAH patients. C57BL/6 mice, vascular smooth muscle cell-specific Grk2 -knockout mice ( Grk2ΔSM22 ), and littermate controls ( Grk2flox/flox ) were grouped into control and hypoxia mice ( n  = 8). Pulmonary hypertension (PH) was induced by exposure to chronic hypoxia (10%) combined with injection of the SU5416 (cHx/SU). The expression levels of GRK2 and Yes-associated protein (YAP) in pulmonary arteries and PASMCs were detected by Western blotting and immunofluorescence staining. The mRNA expression levels of Grk2 and Yes-associated protein ( YAP ) in PASMCs were quantified with real-time polymerase chain reaction (RT-PCR). Wound-healing assay, 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, and 5-Ethynyl-2'-deoxyuridine (EdU) staining were performed to evaluate the proliferation and migration of PASMCs. Meanwhile, the interaction among proteins was detected by immunoprecipitation assays.
RESULTS: The expression levels of GRK2 were upregulated in the pulmonary arteries of patients with PAH and the lungs of PH mice. Moreover, cHx/SU-induced PH was attenuated in Grk2ΔSM22 mice compared with littermate controls. The amelioration of PH in Grk2ΔSM22 mice was accompanied by reduced pulmonary vascular remodeling. In vitro study further confirmed that GRK2 knock-down significantly altered hypoxia-induced PASMCs proliferation and migration, whereas this effect was severely intensified by overexpression of GRK2 . We also identified that GRK2 promoted YAP expression and nuclear translocation in PASMCs, resulting in excessive PASMCs proliferation and migration. Furthermore, GRK2 is stabilized by inhibiting phosphorylating GRK2 on Tyr86 and subsequently activating ubiquitylation under hypoxic conditions.
CONCLUSION: Our findings suggest that GRK2 plays a critical role in the pathogenesis of PAH, via regulating YAP expression and nuclear translocation. Therefore, GRK2 serves as a novel therapeutic target for PAH treatment.
PROBLEM TO BE SOLVED: To obtain a drug delivery system having an upper layer, a control membrane forming an internal chamber and a lower layer, housing an interferon in the chamber and capable of locally and subcutaneously delivering a drug to a skin cancer, a lesion and infectious disease without introducing the drug into the blood stream. SOLUTION: This percutaneous drug delivery system 10 is a multilayered polymeric patch having an upper layer 20 and a lower layer 30. The upper layer 20 is preferably prepared from an impermeable polymer or a foil in order to prevent the drug passing through the tip of the delivery system 10 from leaking. The lower layer 30 functions as a release sheet covering one or more regions of a bonding material 40. When the delivery system 10 is stuck to skin, the lower layer 30 is arranged in directly adjacent to the skin. The upper layer 20 is sealed with a control membrane 50 so as to create the first chamber 60 and the second chamber 70. The drug is preferably selected from griseofulvin, ketoconazole, etc.
Attachment of O-glycans to proteins is controlled by a large family of homologous polypeptide GalNAc-transferases. Polypeptide GalNAc-transferases contain a C-terminal sequence with similarity to lectins. This invention discloses that the putative lectin domains of GalNAc-transferase isoforms, GalNAc-T4, -T7, -T2, and  T3, are functional and recognize carbohydrates, glycopeptides, and peptides. These lectin domains have different binding specificities and modulate the functions of GalNAc-transferase isoforms differently. The lectin domains of GalNAc-T- and -T7 directs the glycopeptide specificities of these enzymes, while the lectin domains of GalNAc-T2 and -T3 directs broadening of donor substrate specificities to include UDP-Gal. Selective inhibitors of these functions that do not eliminate general catalytic activities are disclosed. Such inhibitors disclosed include free sugars, aryl-sugar derivatives, and glycopeptides. Inhibitors of GalNAc-transferase lectin domains are useful for altering the O-glycosylation capacity of cells, tissues, and organisms, and such agents may also interfere with other binding functions involved in intracellular sorting and secretion events.
The present disclosure provides genetically modified microorganisms (e.g., bacteria or yeast) with enhanced mucin-binding and/or cell-adhesion properties. For example, the present disclosure provides bacteria exhibiting increased in vitro binding to Caco-2 cells, and increased in vitro binding to mucins. Such microorganisms (e.g., bacteria) can be used, e.g., to deliver bioactive polypeptides to the gastrointestinal tract of a mammalian subject. Modifying the microorganism in the described manner allows for the modulation of gastrointestinal retention and transit times for the microorganism (e.g., bacterium). Exemplary microorganisms (e.g., lactic acid bacteria, such as Lactococcus lactis) contain an exogenous nucleic acid encoding a fusion protein containing a cell-adherence polypeptide, such as CmbA, and a mucin-binding polypeptide, such as a trefoil factor (TFF), e.g., human TFF3. The current disclosure further provides method for making and using the described microorganisms (e.g., bacteria).
The invention discloses a probiotic strain for reducing blood uric acid, a composition and application thereof. The purine-reducing ability of probiotics is screened under the condition of rich culture medium for the first time, and a culture environment relative to a simulated human intestinal tract is obtained to obtain lactobacillus reuteri KLR-1 with the preservation number of CGMCC No.18699, lactobacillus reuteri strain of Lactobacillus reuteri KLR-3, CGMCC No.18700, lactobacillus reuteri strain of Lactobacillus reuteri KLR-13 and CGMCC No. 19329. Meanwhile, the probiotic composition provided by the invention comprises at least one of the probiotics. The probiotics or the composition has obvious effect of reducing uric acid in an animal model, the probiotics are mutually coordinated, and the effect of reducing uric acid in blood of the composition is obviously better than that of a single probiotic. Has wide application prospect as a new means for reducing blood uric acid and treating gout.
Fimasartan 60 mg + amlodipine besylate 5 mg. In subjects with a DBP equal to or greater than 90 mmHg and / or SBP equal to or greater than 140 mmHg at week 8, the investigator will have the option, according to his clinical criteria, to add 12.5 mg of HCTZ QD (in these cases, the subject will receive one 60 mg Fimasartan tablet plus 12.5 mg HCTZ plus one 5 mg amlodipine besylate tablet.
JAK2/STAT3/MYC axis is dysregulated in nearly 70 % of human cancers, but targeting this pathway therapeutically remains a big challenge in cancer therapy. In this study, genes associated with JAK2, STAT3, and MYC were analyzed, and potential target genes were selected. Leucine-rich PPR motif-containing protein (LRPPRC) whose function and regulation are not fully understood, emerged as one of top 3 genes in terms of RNA epigenetic modification. Here, we demonstrate LRPPRC may be an independent prognostic indicator besides JAK2, STAT3, and MYC. Mechanistically, LRPPRC impairs N6-methyladenosine (m6A) modification of JAK2, STAT3, and MYC to facilitate nuclear mRNA export and expression. Meanwhile, excess LRPPRC act as a scaffold protein binding to JAK2 and STAT3 to enhance stability of JAK2-STAT3 complex, thereby facilitating JAK2/STAT3/MYC axis activation to promote esophageal squamous cell carcinoma (ESCC) progression. Furthermore, 5,7,4'-trimethoxyflavone was verified to bind to LRPPRC, STAT3, and CDK1, dissociating LRPPRC-JAK2-STAT3 and JAK2-STAT3-CDK1 interaction, leading to impaired tumorigenesis in 4-Nitroquinoline N-oxide induced ESCC mouse models and suppressed tumor growth in ESCC patient derived xenograft mouse models. In summary, this study suggests regulation of m6A modification by LRPPRC, and identifies a novel triplex target compound, suggesting that targeting LRPPRC-mediated JAK2/STAT3/MYC axis may overcome JAK2/STAT3/MYC dependent tumor therapeutic dilemma.
The stepped-care arm of this study included an obesity medication intervention. At the start of the study, the active medication was sibutramine and was compared to a placebo control. On 10/8/2010, Abbott Laboratories withdrew their obesity drug sibutramine (Meridia) from the market in light of clinical trial data pointing to an increased risk for stroke and myocardial infarction. In response to this event, the investigators submitted an IRB amendment to change the active obesity medication from sibutramine to Orlistat. The IRB amendment was approved on 11/4/2010. The PI received approval from NIH/NIDDK Program Officer Robert Kuczmarski to enact this change.
Dantrium (dantrolene sodium) has a potential for hepatotoxicity, and should not be used in conditions other than those recommended. Symptomatic hepatitis (fatal and non-fatal) has been reported at various dose levels of the drug. The incidence reported in patients taking up to 400 mg/day is much lower than in those taking doses of 800 mg or more per day. Even sporadic short courses of these higher dose levels within a treatment regimen markedly increased the risk of serious hepatic injury. Liver dysfunction as evidenced by blood chemical abnormalities alone (liver enzyme elevations) has been observed in patients exposed to Dantrium for varying periods of time. Overt hepatitis has occurred at varying intervals after initiation of therapy, but has been most frequently observed between the third and twelfth month of therapy. The risk of hepatic injury appears to be greater in females, in patients over 35 years of age, and in patients taking other medication(s) in addition to Dantrium (dantrolene sodium). Spontaneous reports suggest a higher proportion of hepatic events with fatal outcome in elderly patients receiving Dantrium. However, the majority of these cases were complicated with confounding factors such as intercurrent illnesses and/or concomitant potentially hepatotoxic medications (see Geriatric Use subsection). Dantrium should be used only in conjunction with appropriate monitoring of hepatic function including frequent determination of SGOT or SGPT. If no observable benefit is derived from the administration of Dantrium after a total of 45 days, therapy should be discontinued. The lowest possible effective dose for the individual patient should be prescribed.
Cancer is the leading cause of death among Latinos in the U.S. While engaging in a physically active lifestyle is one of the most important modifiable behaviors for reducing cancer risk; few Latinas achieve health-enhancing levels of physical activity (PA) recommended by the National PA Guidelines, particularly for muscle strengthening activities (MSA). For instance, 44% of Latinas meet the national guidelines for aerobic PA but only 17% meet the full guidelines for both aerobic and MSA. While the benefits of aerobic MVPA are well established for cancer and chronic disease prevention, participating in regular MSA may be key to further reducing cancer risk, as adherence to MSA guidelines has been associated with a 19% to 31% lower cancer mortality risk, independent of aerobic PA. There is a need for interventions promoting MSA in Latinas. However, only a select few MSA interventions have included Latinas in their sample, and none to the investigators' knowledge, were designed exclusively for this population or addressed socio-cultural factors influencing Latinas' muscle strengthening behaviors (e.g., perception that MSA is for men; MSA is an avoided topic in their culture and social circles; belief that women should only do certain types of MSA). Moreover, existing interventions often involved in-person exercise programs, which can be inaccessible to many Latinas due to barriers such as lack of transportation or fear of immigration enforcement. The research team has previously developed and tested aerobic moderate-to-vigorous PA (MVPA) interventions for Latinas that overcome barriers to in-person programs and address PA-related socio-cultural factors. These theory-driven, individually tailored interventions have shown success at increasing aerobic MVPA among Latina women in both print and Internet-based randomized controlled trials, and now provide an ideal platform for promoting MSA in this at-risk population. To address the gap in literature on MSA, the investigators recently conducted qualitative interviews with 19 Latinas to identify theory-based barriers and facilitators of muscle strengthening PA, then developed MSA intervention materials and further refined them for cultural appropriateness, relevance, and appeal in Latinas. In the proposed research, the investigators will incorporate the newly developed MSA promotion materials into the existing web-based aerobic MVPA intervention and conduct a 12-week fully online randomized pilot trial testing the preliminary efficacy of the newly adapted web-based aerobic plus MSA intervention for Latinas. Fifty Latina adults (i.e., aged 18-65 years) will be randomized to either the: 1) original aerobic MVPA intervention arm, or 2) aerobic MVPA plus MSA intervention arm. This study aims to: 1) Assess the preliminary efficacy of the aerobic plus MSA intervention for increasing MSA, and 2) Explore potential mediators and moderators of MSA. This interactive and highly disseminable approach can achieve significant health improvements in an at-risk population.
Decreased intake is induced by stressors such as parturition, transportation, dietary transitions, and disease. An important function of one-carbon metabolism (OCM) is to produce the antioxidant glutathione to help reduce oxidative stress. Although various components of OCM are expressed in the bovine rumen and small intestine, the relationship between reduced feed intake, OCM, and antioxidant mechanisms in gut tissues is unknown. This study aimed to assess alterations in immune and antioxidant pathways in ruminal epithelium due to acute feed restriction (FR). Seven group-housed ruminally cannulated Angus steers (663 ± 73 kg body weight, 2 yr old) had ad libitum access to a finishing diet (dry-rolled corn, corn silage, modified wet distiller's grains) during 15 d of a pre-FR period (PRE). Subsequently, steers were moved to a metabolism barn with tie stalls and individually fed at 25% of estimated intake in PRE for 3 d (FR period, FRP). This was followed by 15 d of recovery (POST) during which steers had ad libitum access to the same diet as in PRE and FRP. Plasma and ruminal tissue biopsies were collected during each period. Plasma free fatty acid and IL1-β concentrations were higher (P ≤ 0.03) in FRP than PRE or POST. The mRNA abundance of the proinflammatory genes tumor necrosis factor, toll-like receptor 2 (TLR2), and TLR4 in the ruminal epithelium peaked (P < 0.05) at FRP and remained higher at POST. These responses agreed with the higher (P < 0.05) abundance of phosphorylated (p)-MAPK (an inflammation activator) and p-EEF2 (translational repressor) in FRP than PRE and POST. Although ruminal glutathione peroxidase (GPX) enzyme activity did not increase at FRP compared with PRE and POST, protein abundance of GPX1 and GPX3 along with the antioxidant response regulator NFE2L2 were highest (P < 0.01), and the activity of cystathionine-beta synthase tended (P = 0.06) to be highest during FR. Although FR had minimal negative effects on tissue integrity-related genes (only filamin A was downregulated), it led to a systemic inflammatory response and triggered inflammation and antioxidant mechanisms within the ruminal epithelium. Thus, deploying anti-inflammatory and antioxidant mechanisms via molecules that feed into OCM (e.g., dietary methyl donors such as methionine, choline, betaine, and folate) could potentially counteract the stressors associated with FR.
Patients in whom a bone marrow biopsy is planned will be randomised to one of two groups - a control-TENS group where the TENS machine will be set at the lowest sensory threshold and an intervention-TENS group where the TENS machine will be set at a recognised analgesic level (\>50 Hertz (Hz) and below the pain threshold for the patient) (Bennett et al. 2011). The identity of the TENS type will be concealed from both the patient and the doctor performing the biopsy. The primary outcome will be pain and this will be recorded by the patient immediately after the procedure using a validated numerical scale (0-10). All patients will receive standard pain relief (ie. local anaesthetic with or without inhaled nitrous oxide).

The benefit of this study is to establish whether or not TENS can benefit patients as an additional, safe, non-invasive and inexpensive method of pain relief during this frequently painful procedure.