anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
BACKGROUND: Thoracic aortic dissection (TAD) is one of the most fatal cardiovascular diseases. One of its important pathological characteristics is the local inflammatory response. Many studies have found that Macrophage polarization plays an extremely critical role in the inflammatory progression and tissue remodeling of TAD. Costunolide (CTD) has an improving effect on oxidative stress and inflammation in the body. However, whether it can promote the integrity of extracellular matrix in Aortic dissection and its mechanism are still unclear.
METHODS: The male C57BL/6J mice were used to construct an animal model of TAD with β-aminopropionitrile (BAPN) (100 mg/kg/day, lasting for 28 days), and then CTD (10 mg/kg or 100 mg/kg) was injected intraperitoneally for 28 days to check the survival rate, TAD incidence, aortic morphology and other indicators of the mice. Using hematoxylin-eosin (HE), Masson, Elastin van Gieson (EVG) staining, immunofluorescence (IF), and immunohistochemical staining, the study aimed to determine the therapeutic effects of CTD on an animal model with BAPN-induced TAD. To enhance the examination of the regulatory mechanism of CTD, we conducted transcriptome sequencing on arterial tissues of mice in both the BAPN group and the BAPN + CTD100 group. Next, ANG II were used to construct TAD model in vascular smooth muscle cells (VMSCs). The effects of CTD on the proliferation, migration, invasion, and apoptosis of ANG II-induced cells are to be detected. The expression of MMP2, MMP9, P65, and p-P65 in each group will be examined using Western blot. Finally, the overexpression of IκB kinaseβ (IKKβ) will be established in VMSCs cells to further explore the protective function of CTD.
RESULTS: The result showed that CTD significantly inhibited BAPN induced mortality and TAD incidence in the animal model, improved aortic vascular morphology, promoted the integrity of extracellular matrix in TAD, reduced tissue inflammation, reduced the accumulation of M1 macrophage, promoted M2 macrophage polarization, and reduced the expression of NF-κB pathway related proteins. Mechanistically, CTD significantly weakened the proliferation, migration, invasion, and apoptosis. p-P65 protein expression of TAD cells were induced by ANG II and IKK-β.
CONCLUSION: CTD has the potential to alleviate inflammation, VSMC apoptosis, MMP2/9 levels, and enhance extracellular matrix integrity in TAD by inhibiting the NF-κB signaling pathway.
Neuropathic pain is a type of chronic pain that entails severe prolonged sensory dysfunctions caused by a lesion of the somatosensory system. Many of those suffering from the condition do not experience significant improvement with existing medications, resulting in various side effects. In this study, Sprague-Dawley male rats were used, and long-term deep brain stimulation of the ventrolateral periaqueductal gray was conducted in a rat model of spared nerve injury. We found that 5-Hz deep brain stimulation effectively modulated mechanical allodynia and induced neuronal activation in the rostral ventromedial medulla, restoring impaired descending serotonergic system. At the spinal level, glial cells were still activated but only the 5-HT1a receptor in the spinal cord was activated, implying its inhibitory role in mechanical allodynia. This study found that peripheral neuropathy caused dysfunction in the descending serotonergic system, and prolonged stimulation of ventrolateral periaqueductal gray can modulate the pathway in an efficient manner. This work would provide new opportunities for the development of targeted and effective treatments for this debilitating disease, possibly giving us lower chances of side effects from repeated high-frequency stimulation or long-term use of medication.
The nutritional fitness of Service Members directly influences recovery from operational stress. Inadequate recovery nutrition following military missions, including sleep loss, exacerbates skeletal muscle loss and contributes to degraded physical performance. Muscle loss and performance declines following stress are in part due to inadequate nutritional fitness, impaired muscle recovery, and negative whole-body protein balance (WBPB). Sleep loss dysregulates anabolic hormones, induces catabolism, and reduces muscle protein synthesis (MPS). However, WBPB has not been assessed following military-relevant sleep loss (i.e., 4h/d) alone. This presents an important knowledge gap given the influence of WBPB on health and readiness. Consuming increased dietary protein following sleep loss could enhance muscle recovery by stimulating MPS and supporting WBPB, but whether protein recovery nutrition counteracts the stress of sleep loss is unknown. Beyond the quantity of protein consumed, optimizing the timing/distribution of daily protein consumption is required to augment anabolism. Consuming a skewed protein distribution results in meals (i.e., breakfast and lunch) that deliver a suboptimal protein quantity for maximally stimulating MPS. Alternatively, targeting an even protein distribution may optimize anabolism and recovery following stress by providing per meal protein quantities that maximally stimulate MPS and support WBPB. The efficacy of manipulating protein distribution for counteracting the stress of sleep loss is unknown. The proposed effort will determine protein nutritional status (MPS and WBPB) in response to military-relevant sleep loss, and whether an even protein nutrition distribution during recovery optimally supports MPS and WBPB. Adults (n=20) will complete a 7d sleep satiated phase (\~7-9h target/d), a 4d military-relevant sleep restriction phase (\~4h /d), and a 3d recovery phase (\~7-9h target/d) in a randomized, parallel design. During recovery, volunteers will consume 1.6 g protein/kg/d as an even (\~0.4/0.4/0.4/0.4 g/kg) or skewed (\~0.11/0.27/1.15/0.07 g/kg) distribution. Sleep will be monitored throughout the study using wrist actigraphy and diaries. During each phase, integrated daily MPS will be estimated using ingested deuterium oxide, salivary and blood sampling, and muscle biopsies, while WBPB will be estimated using ingested 15-N alanine and urine collections. At the end of each phase, metabolic testing will be used to assess the effects of sleep loss on substrate utilization and include consuming a carbohydrate beverage, serial blood draws, indirect calorimetry, and steady-state aerobic exercise. The knowledge products derived from the proposed effort will be informative to next generation ration development and support military-specific recovery nutrition guidance following operations involving sleep loss.
The impact of carbohydrates, proteins and fatty acids as major components of daily nutrition on the development of metabolic illnesses is an objective of numerous clinical studies. However, the effect of an isocaloric diet on metabolism is less investigated and not well understood. This study aims to reveal genetic determinated metabolic responses to an isocaloric high carbohydrate, low fat diet versus an isocaloric low carbohydrate, high fat diet in healthy twins. This study generates information for further detailed nutrigenomic analysis. Twins receive an isocaloric diet rich in carbohydrates (55% carbohydrates, 15% protein, 30% fat) with dietary counselling for 5 weeks and afterwards with nutrients supplied for 6 days, followed by an isocaloric diet rich in saturated fat (40% carbohydrates, 15% protein, 45% fat) for 6 days with nutrients supplied and for 4 weeks with dietary counselling and again followed by another 6 days when nutrients were supplied. Anthropometry, blood tests and energy expenditure are performed after the period of diet rich in carbohydrates (Carb), after the first 6 days (HFshort) and at the end of the period of diet rich in fat (HFlong).
1,193,288. 4,12-Aza-tetracyclines. CHINOIN GYOGYSZER ES VEGYESZETI TERMEKEK GYARA RT. 9 Aug., 1967 [9 Aug., 1966; 6 July, 1967], No. 36643/67. Heading C2A. The invention comprises 4,12-azatetracyclinium compounds of Formula I wherein X is H or CH 3 , Y is H or halogen and Z<SP>-</SP> is the anion of an acid; and the corresponding betaine salts of Formula II wherein X and Y have the above meanings. Compounds of Formula I are obtained by treating compounds of Formula V with an acid e.g. a sulphonic or hydrohalic acid at a pH not greater than 2À0 in an alkanol at a temperature of 110-140 C. If the tetracycline is used in the form of the hydrochloride, an alkyl ester of a sulphonic acid or 1,3 propane sultone may be used. Zinc chloride may be used as a catalyst. Betaines of Formula II are prepared by reacting compounds of Formula I with a base e.g. an alkali metal bicarbonate, ammonium bicarbonate, an alkali metal acetate or an organic base especially hexamethylene tetramine. Compound I is reformed by treating the betaine II with an acid. A typical compound is 4 - desdimethylamino - 5a,6 - anhydro - 6- demethyl - 7 - chloro - 12 - deoxy - [(N - dimethyl) - 4,12 - aza] - tetracyclinium benzene sulphonate. A pharmaceutical composition comprises a tetracycline antibiotic of Formula I or II and a carrier for oral, parenteral, rectal or topical administration.
R21 with Matrix-M1, ChAd63 ME-TRAP and MVA ME-TRAP. Three vaccinations with 10 µg R21/ 50 µg Matrix-M1 on days 0 , 28 and 56. Plus one vaccination with ChAd63 ME-TRAP on day 7 and one vaccination with MVA ME-TRAP on day 63.
Thaumatin-like proteins (TLPs) in plants play a crucial role in combating stress, and they have been proven to possess antifungal properties. However, the role of TLPs in pathogens has not been reported. We identified a effector protein, Pt9029, which contained a Thaumatin domain in Puccinia triticina (Pt), possessing a chloroplast transit peptide and localized in the chloroplasts. Silencing Pt9029 in the Pt physiological race THTT resulted in a notable reduction in virulence and stunted growth and development of Pt hypha in near-isogenic wheat line TcLr2b. Overexpression of Pt9029 in wheat exerted a suppressive effect on H2O2 production, consequently impeding the wheat's disease resistance mechanisms. The TLP domain of Pt9029 targets the Rubisco activase (TaRCA) in chloroplasts. This interaction effectively inhibited the function of TaRCA, subsequently leading to a decrease in Rubisco enzyme activity. Therefore, this indicates that TLPs in Pt can inhibit host defense mechanisms during the pathogenic process of Pt. Moreover, TaRCA silencing resulted in reduced resistance of TcLr2b against Pt race THTT. This clearly demonstrated that TaRCA positively regulates wheat resistance to leaf rust. These findings reveal a novel strategy exploited by Pt to manipulate wheat rust resistance and promote pathogenicity.
Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory disorder with environmental factors being the primary risk determinants. However, genetic factors also substantially contribute to the susceptibility and progression of COPD. Although genome-wide association studies (GWAS) have identified several loci associated with COPD susceptibility, the specific pathogenic genes underlying these loci, along with their biological functions and roles within regulatory networks, remain unclear. This lack of clarity constrains our ability to achieve a deeper understanding of the genetic basis of COPD. This study leveraged the FinnGen R11 genetic dataset, comprising 21,617 cases and 372,627 controls, along with GTEx V8 eQTLs data to conduct a cross-tissue transcriptome-wide association study (TWAS). Initially, we performed a cross-tissue TWAS analysis using the Unified Test for Molecular Signatures (UTMOST), followed by validation of the UTMOST findings in single tissues using the Functional Summary-based Imputation (FUSION) method and conditional and joint (COJO) analyses of the identified genes. Subsequently, candidate susceptibility genes were screened using Multi-marker Analysis of Genomic Annotation (MAGMA). The causal relationship between these candidate genes and COPD was further evaluated through summary data-based Mendelian randomization (SMR), colocalization analysis, and Mendelian randomization (MR). Additionally, the identified results were validated against the COPD dataset in the GWAS Catalog (GCST90399694). GeneMANIA was employed to further explore the functional significance of these susceptibility genes. In the cross-tissue TWAS analysis (UTMOST), we identified 17 susceptibility genes associated with COPD. Among these, a novel susceptibility gene, G protein-coupled receptor kinase 4 (GRK4), was validated through single-tissue TWAS (FUSION) and MAGMA analyses, with further confirmation via SMR, MR, and colocalization analyses. Moreover, GRK4 was validated in an independent dataset. This study identifies GRK4 as a potential novel susceptibility gene for COPD, which may influence disease risk by exacerbating inflammatory responses. The findings address gaps in previous single-tissue GWAS studies, revealing consistent expression and potential function of GRK4 across different tissues. However, considering the study's limitations, further investigation and validation of GRK4's role in COPD are warranted.
PURPOSE: Physical rehabilitation (PR) in the intensive care unit (ICU) may improve outcomes for survivors but clinical trial results have been discordant. We hypothesized that discordant results may reflect treatment heterogeneity received by "usual care" comparator groups in PR studies. Usual-care PR is typically underspecified, which is a barrier to comparing results across treatment studies. The primary objective of the present study was to describe the usual-care PR received by critically ill patients enrolled in the Canadian multicentre Critical Care Cycling to Improve Lower Extremity Strength (CYCLE) pilot randomized controlled trial (RCT) of PR. Other objectives were to help contextualize current research and provide data for international comparison.
METHODS: In this secondary analysis of the CYCLE pilot RCT, patients were randomized to in-bed cycling and usual-care PR or usual-care PR alone. Physiotherapists documented usual-care PR including therapy received, type of activity, duration, adverse events and consequences, reasons for no PR, and concurrent relevant medical interventions. We characterized usual care using descriptive statistics at the cohort and patient levels.
RESULTS: Across seven Canadian centres, 30 patients were randomized to usual-care PR. The median [interquartile range (IQR)] ICU stay was 10 [9-24] days and patients received PR on a median [IQR] of 5 [3-9] days for 23 [17-30] min per day. Eighteen patients (60%) stood, marched, or walked during usual care. Transient adverse events occurred in three patients on 1.5% (3/198) of days and none prompted session termination.
CONCLUSIONS: In the usual-care arm of the CYCLE pilot RCT, PR was delivered on half of ICU days and over half of patients stood, marched, or walked. Adverse events during usual-care PR were uncommon.
STUDY REGISTRATION: ClinicalTrials.gov ( NCT02377830 ); first posted 4 March 2015.
In chronic wound treatment, the debridement of devitalized tissue and the eradication of the biofilm must balance aggressiveness with care to protect regenerating tissues. In this study, urea, a potent chaotropic molecule, was modulated through the formation of a Natural Deep Eutectic Solvent (NADES) with betaine to develop a new debriding material (BU) suitable for application into injured dermal tissues. To evaluate BU's debriding capacity, along with its antibiofilm effect and biocompatibility, pre-clinical to clinical methods were employed. In vitro determinations using artificial and clinical slough samples indicate that BU has a high debriding capacity. Additionally, BU's de-structuring effects lead to a strong antibiofilm capability, demonstrated by a reduced bacterial load compared to the antiseptic PHMB-Betaine or medical honey, evaluated in artificial slough and ex vivo human skin. Furthermore, BU's efficacy was evaluated in a murine model of diabetic wound, demonstrating significant effects on debriding and antibiofilm capacity, similar to those observed in PHMB-Betaine and medical honey-treated animals. Finally, BU was clinically evaluated in leg ulcers, showing superiority in reduction of bacterial load and wound area compared to honey, with no adverse effects. Thus, BU represents a simple and non-biocidal option that could contributes to chronic wound care.
BACKGROUND: Limited data exists regarding the mortality of very low birth weight (VLBW) neonates with congenital diaphragmatic hernia (CDH). This study aims to quantify and determine predictors of mortality in VLBW neonates with CDH.
METHODS: This analysis of 829 U.S. NICUs included VLBW [birth weight ≤1500g] neonates, born 2011-2021 with and without CDH. The primary outcome was in-hospital mortality. A generalized estimating equation regression model determined the adjusted risk ratio (ARR) of mortality.
RESULTS: Of 426,140 VLBW neonates, 535 had CDH. In neonates with CDH, 48.4% had an additional congenital anomaly vs 5.5% without. In-hospital mortality for neonates with CDH was 70.4% vs 12.6% without. Of those with CDH, 73.3% died by day of life 3. Of VLBW neonates with CDH, 38% were repaired. A subgroup analysis was performed on 60% of VLBW neonates who underwent delivery room intubation or mechanical ventilation, as an indicator of active treatment. Mortality in this group was 62.7% for neonates with CDH vs 16.4% without. Higher Apgars at 1 min and repair of CDH were associated with lower mortality (ARR 0.91; 95%CI 0.87,0.96 and ARR 0.28; 0.21,0.39). The presence of additional congenital anomalies was associated with higher mortality (ARR 1.14; 1.01,1.30).
CONCLUSION: These benchmark data reveal that VLBW neonates with CDH have an extremely high mortality. Almost half of the cohort have an additional congenital anomaly which significantly increases the risk of death. This study may be utilized by providers and families to better understand the guarded prognosis of VLBW neonates with CDH.
TYPE OF STUDY: Level II.
LEVEL OF EVIDENCE: Level II.
Obesity is a metabolic disorder closely associated with profound alterations in gut microbial composition. However, the dynamics of species composition and functional changes in the gut microbiome in obesity remain to be comprehensively investigated. In this study, we conducted a meta-analysis of metagenomic sequencing data from both obese and non-obese individuals across multiple cohorts, totaling 1351 fecal metagenomes. Our results demonstrate a significant decrease in both the richness and diversity of the gut bacteriome and virome in obese patients. We identified 38 bacterial species including Eubacterium sp. CAG:274, Ruminococcus gnavus, Eubacterium eligens and Akkermansia muciniphila, and 1 archaeal species, Methanobrevibacter smithii, that were significantly altered in obesity. Additionally, we observed altered abundance of five viral families: Mesyanzhinovviridae, Chaseviridae, Salasmaviridae, Drexlerviridae, and Casjensviridae. Functional analysis of the gut microbiome indicated distinct signatures associated to obesity and identified Ruminococcus gnavus as the primary driver for function enrichment in obesity, and Methanobrevibacter smithii, Akkermansia muciniphila, Ruminococcus bicirculans, and Eubacterium siraeum as functional drivers in the healthy control group. Additionally, our results suggest that antibiotic resistance genes and bacterial virulence factors may influence the development of obesity. Finally, we demonstrated that gut vOTUs achieved a diagnostic accuracy with an optimal area under the curve of 0.766 for distinguishing obesity from healthy controls. Our findings offer comprehensive and generalizable insights into the gut bacteriome and virome features associated with obesity, with the potential to guide the development of microbiome-based diagnostics.
A method for tracking patient data allows practitioners to increase patient care effectiveness. The method includes providing a host computer for storing data thereon, transmitting the patient data to the host computer via a network, storing the patient data on the host computer, and providing access to the patient data via a client computer. In one embodiment, storing patient data includes storing a treatment plan for a patient. The method may also include tracking patient compliance with the treatment plan. In another aspect of the present invention, an apparatus for integrated patient care includes a patient module that displays a treatment plan on a client computer, a practitioner module that monitors the progress of the patient in following the treatment plan, and an office module that transmits billing statements for the treatment plan to an insurance carrier. The present invention facilitates increased patient contact with practitioners and increased treatment effectiveness.
<P>PROBLEM TO BE SOLVED: To regulate inflammatory cytokine production by exogenous factors such as ghrelin to ameliorate a wide variety of ailments and disease conditions.  <P>SOLUTION: There is provided a method of inhibiting proinflammatory cytokine expression using ghrelin. Also, there is provided a method of treating loss of appetite comprising a process of administering ghrelin or a fragment thereof. Also, there is provided a method of treating sepsis comprising a process of administering ghrelin or a fragment thereof. There is provided a method of treating inflammation in a subject comprising a process of administering to the subject an effective amount of ghrelin.  <P>COPYRIGHT: (C)2011,JPO&INPIT
In adults, high doses of digoxin may produce a variety of electrocardiographic changes and rhythm disturbances, such as first-degree, second-degree (Wenckebach), or third-degree heart block (including asystole); atrial tachycardia with block; AV dissociation; accelerated junctional (nodal) rhythm; unifocal or multifocal ventricular premature contractions (especially bigeminy or trigeminy); ventricular tachycardia; and ventricular fibrillation. Prophylactic use of a cardiac pacemaker may be considered if the risk of heart block is considered unacceptable.

In pediatric patients, the use of digoxin may produce arrhythmias. The most common are conduction disturbances or supraventricular tachyarrhythmias, such as atrial tachycardia (with or without block) and junctional (nodal) tachycardia. Ventricular arrhythmias are less common. Sinus bradycardia may be a sign of impending digoxin intoxication, especially in infants, even in the absence of first-degree heart block. Any arrhythmias or alteration in cardiac conduction that develops in a child taking digoxin should initially be assumed to be a consequence of digoxin intoxication.
The decrease in functional capacity is a finding that affects quality of life in chronic liver diseases. In a study, 6 Minute Walk Test was associated with mortality in patients with cirrhosis and survival was lower in patients walking less than 250 meters. Malnutrition is a common complication of end-stage liver disease. It is a complex condition that causes loss of muscle and fat mass, loss of body weight, increased pro-inflammatory cytokines, anorexia and fatigue, resulting in sarcopenia. Sarcopenia is generally defined as a loss of muscle mass and muscle strength and is directly related to adverse outcomes in these patients. In the evaluation of malnutrition in end-stage liver disease, evaluation of skeletal muscle (mass, strength, functionality) provides an objective way to determine malnutrition, since most intrinsic markers originate from existing liver disease (eg albumin, prealbumin, lymphopenia levels).