anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Muscle spasms are common in chronic spinal cord injury (SCI), posing challenges to rehabilitation and daily activities. Pharmacological management of spasms mostly targets suppression of excitatory inputs, an approach known to hinder motor recovery. To identify better targets, we investigated changes in inhibitory and excitatory synaptic inputs to motoneurons as well as motoneuron excitability in chronic SCI. We induced either a complete or incomplete SCI in adult mice of either sex and divided those with incomplete injury into low or high functional recovery groups. Their sacrocaudal spinal cords were then extracted and used to study plasticity below injury, with tissue from naive animals as a control. Electrical stimulation of the dorsal roots elicited spasm-like activity in preparations of chronic severe SCI but not in the control. To evaluate overall synaptic inhibition activated by sensory stimulation, we measured the rate-dependent depression of spinal root reflexes. We found inhibitory inputs to be impaired in chronic injury models. When synaptic inhibition was blocked pharmacologically, all preparations became clearly spastic, even the control. However, preparations with chronic injuries generated longer spasms than control. We then measured excitatory postsynaptic currents (EPSCs) in motoneurons during sensory-evoked spasms. The data showed no difference in the amplitude of EPSCs or their conductance among animal groups. Nonetheless, we found that motoneuron persistent inward currents activated by the EPSCs were increased in chronic SCI. These findings suggest that changes in motoneuron excitability and synaptic inhibition, rather than excitation, contribute to spasms and are better suited for more effective therapeutic interventions.Significance Statement Neural plasticity following spinal cord injury is crucial for recovery of motor function. Unfortunately, this process is blemished by maladaptive changes that can cause muscle spasms. Pharmacological alleviation of spasms without compromising the recovery of motor function has proven to be challenging. Here, we investigated changes in fundamental spinal mechanisms that can cause spasms post-injury. Our data suggest that the current management strategy for spasms is misdirected toward suppressing excitatory inputs, a mechanism that we found unaltered after injury, which can lead to further motor weakness. Instead, this study shows that more promising approaches might involve restoring synaptic inhibition or modulating motoneuron excitability.
This study is a double-blind randomized controlled trial designed to assess the efficacy of GCBT compared to a waiting group for mental sub-health. Participants will be randomly (1:1) assigned to the GCBT group and the waiting group. All participants will receive 4 sessions (1 session per week) of 90 minutes each for 4 weeks.The GCBT group will receive cognitive behavioral therapy at the 1st-4th weeks, while the waiting group will receive cognitive behavioral therapy at the 5th-8th weeks. Before GCBT (baseline) and after GCBT (4th weeks, 8th weeks, 28th weeks), both groups will be assessed for clinical symptoms; during the 4 weeks of the intervention, we will collect sensor data and daily diary feedback. The GCBT is mainly divided into four stages, and each stage has a topic. The topic of each stage as follow:# understanding depression, anxiety, and CBT;# understanding automatic thinking and negative automatic thinking;# identifying and correcting negative automatic thinking identification; identifying and correcting intermediate beliefs;#understanding core beliefs and mastering correction techniques.The purposes of the present study are to: 1) evaluate the clinical response the GCBT in mental sub-health. 2) further understand the possible biological mechanism underlying the efficacy of GCBT by analyzing digital biomarkers.
Obesity is now a significant global public health issue. Limited understanding exists regarding the association between obesity and concomitant exotropia. Our objective was to identify the causal relationship between lifecourse obesity, including birth weight, childhood body mass index (BMI), and adult BMI, and the risk of concomitant exotropia. We used a two-sample Mendelian randomization (MR) strategy to examine the causal relationship with inverse-variance weighted method as the primary MR analysis. We carried out sensitivity analyses to evaluate the accuracy and robustness of our findings. Also, we performed reverse-direction MR analysis to eliminate the possibility of reverse causality. Childhood BMI, as opposed to birth weight or adult BMI, had a significant impact on the risk of concomitant exotropia (odds ratio = 1.40, 95% confidence interval (CI): 1.08-1.81, P = .01). This significance persisted even after accounting for birth weight and adult BMI using multivariable MR analysis (odds ratio = 1.35, 95% CI: 1.04-1.75, P = .02). There was no significant heterogeneity or pleiotropy observed in sensitivity analyses (P > .05). Multivariable MR analysis further confirmed the absence of pleiotropic effects of some risk factors including prematurity, maternal smoking around birth and refractive error. Reverse causality did not affect the causal relationship (beta = -0.0244, 95% CI: -0.0545 to 0.0056, P = .11). Genetic predisposition to higher childhood BMI was found to be causally linked to an increased risk of concomitant exotropia.
One of the major problems in the expanding population of patients with congenital heart disease (CHD) is dysfunction of the right ventricular (RV) outflow tract (OT). Initial surgical repair for complex conditions or repeated surgery for free pulmonary regurgitation often includes the creation of an artificial RV to main pulmonary artery connection. Over time, these conduits are prone to develop valvar incompetence or obstruction. There is clear evidence that pulmonary stenosis and pulmonary regurgitation are associated with exercise intolerance, arrhythmias and an increased risk of sudden death. Timely pulmonary valve replacement can halt and may reverse such unfavourable outcomes. However, this means that patients have to undergo multiple open-heart surgeries in order to reduce the haemodynamic burden on the right ventricle. Decision making in these patients with RVOT dysfunction is based on the aim to perform pulmonary valve replacement as late as possible to minimise the total number of open-heart surgeries required in individual patients, but before functional impairment might be irreversible. Importantly, this point of 'no return' in right ventricular pressure and/or volume overload is still unknown and represents one of the most challenging problems in the field of CHD. Ideally, quality of life, survival and freedom from atrial and ventricular arrhythmia should be the endpoints for any study trying to optimise timing of pulmonary valve replacement. However, such studies would require long follow-up in large patient populations and will not help to improve management of right ventricular outflow tract (RVOT) dysfunction in the short-term. In order to design studies with surrogate functional endpoints, a sound understanding of physiological consequences of altering RV loading and its implications for bi-ventricular function or exercise capacity is pivotal.

The investigators established a method of acquiring robust RV pressure-volume-loops at our institution. In the context of a research study, the investigators performed RV conductance catheter measurements in 22 patients with heart failure with preserved ejection fraction and in 11 patients with no evidence of any RV disease. Within the RaDICAL study the investigators aim further to compare these results to pressure-volume loops acquired in patients with congenital heart disease (CHD) and adverse RV loading conditions in order to evaluate characteristics, incidence and predictors of load-independent right ventricle (RV) diastolic dysfunction.
Paradoxical embolism is a medical condition characterized by the migration of an embolus from a venous source into the systemic circulation. This occurs through a specific cardiac abnormality known as a right-to-left shunt, ultimately resulting in the possibility of arterial embolism. Patent foramen ovale (PFO) is the most common cause of intracardiac shunting. We reported a rare case of a 56-year-old man on hemodialysis with PFO and arteriovenous fistula dysfunction who suffered a paradoxical embolic ischemic stroke after percutaneous transluminal angioplasty. This case emphasized the potential risk of paradoxical embolism in hemodialysis patients with vascular access problems. We aimed to highlight the importance of searching for PFO, as it may serve as a possible source of embolism in these patients.
Cigarette smoke (CS), an indoor environmental pollutant, is a prominent risk factor for emphysema, which is a pathological feature of chronic obstructive pulmonary disease (COPD). Emerging function of circRNAs in immune responses and disease progression shed new light to explore the pathogenesis of emphysema. In this research, we demonstrated, by single-cell RNA sequencing (scRNAseq), that the ratio of M2 macrophages were increased in lung tissues of humans and mice with smoking-related emphysema. Further, our data showed that circADAMTS6 was associated with cigarette smoke extract (CSE)-induced M2 macrophage polarization. Mechanistically, in macrophages, circADAMTS6 stabilized CAMK2A mRNA via forming a circADAMTS6/IGF2BP2/CAMK2A RNA-protein ternary complex to activate CREB, which drives M2 macrophage polarization and leads to emphysema. In addition, in macrophages of mouse lung tissues, downregulation of circADAMTS6 reversed M2 macrophage polarization, the proteinase/anti-proteinase imbalance, and the elastin degradation, which protecting against CS-induced emphysema. Moreover, for macrophages and in a model with co-cultured lung organoids, the target of circADAMTS6 restored the growth of lung organoids compared to CSE-treated macrophages. Our results also demonstrated that, for smokers and COPD smokers, elevation of circADAMTS6 negatively correlated with lung function. Overall, this study reveals a novel mechanism for circADAMTS6-driven M2 macrophage polarization in smoking-related emphysema and postulates that circADAMTS6 could serve as a diagnostic and therapeutic marker for smoking-related emphysema.
CHD is the leading cause of death in the United States. Anti-platelet agents lessen platelet aggregation and are used commonly to prevent recurrent CHD events. Two of the most common anti-platelet agents are aspirin and clopidogrel. However, up to 25% to 30% of people do not respond to these medications. Evidence indicates that treatment response may be related to genetics. The purpose of this study is to determine specific gene variants that predict response to aspirin and clopidogrel therapy.

This study is part of a larger group of studies called the Pharmacogenomics Research Network (PGRN). Participants will include the Old Order Amish of Lancaster, Pennsylvania. They are well suited for genetic studies because they are a homogenous, closed, founder population. Participants will receive 300 mg of clopidogrel on the first day, then 75 mg of clopidogrel per day for the next 6 days. On the last day of clopidogrel treatment, participants will take a single dose of 324 mg aspirin. Participants will undergo platelet function tests before and after clopidogrel alone, and then again after taking clopidogrel plus aspirin. Using the gene variation profiles across the genome, researchers will analyze which genes correspond to treatment response.
This group will receive an accelerometer and daily step goal. They will monitor their steps over the 9 week duration of the study. They will have the same level of contact as the other two conditions. In addition they will plan when, where, and how they will take steps in inconsistent contexts, i.e., that vary from day to day.
Epilepsy is a complex genetic disorder that affects about 2% of the global population. Although the frequency and severity of epileptic seizures can be reduced by a range of pharmacological interventions, there are no disease-modifying treatments for epilepsy. The development of new and more effective drugs is hindered by a lack of suitable animal models. Available rodent models may not recapitulate all key aspects of the disease. Spontaneous epileptic convulsions were observed in few Göttingen Minipigs (GMPs), which may provide a valuable alternative animal model for the characterisation of epilepsy-type diseases and for testing new treatments. We have characterised affected GMPs at the genome level and have taken advantage of primary fibroblast cultures to validate the functional impact of fixed genetic variants on the transcriptome level. We found numerous genes connected to calcium metabolism that have not been associated with epilepsy before, such as ADORA2B, CAMK1D, ITPKB, MCOLN2, MYLK, NFATC3, PDGFD, and PHKB. Our results have identified two transcription factor genes, EGR3 and HOXB6, as potential key regulators of CACNA1H, which was previously linked to epilepsy-type disorders in humans. Our findings provide the first set of conclusive results to support the use of affected subsets of GMPs as an alternative and more reliable model system to study human epilepsy. Further neurological and pharmacological validation of the suitability of GMPs as an epilepsy model is therefore warranted.
Despite the increased success of novel anti-neoplastic therapies, breast cancer patients receiving chemotherapy develop unfavourable changes in body composition, including lean tissue loss and fat gains (1,2). These detrimental changes associate with poor quality of life (3,4) and may lead to treatment complications (5,6) during the cancer trajectory. In non-malignant populations, fat gain and muscle loss associate with increased risk of cardiovascular disease and diabetes (7). Cancer survivors who gain fat and lose lean mass are not only predisposed to these diseases but also have an increased risk of cancer recurrence (3). Proper nutrition as well as exercise can independently improve metabolic profiles (i.e. immune function, lipid and glucose metabolism) and overall health outcomes in non-malignant populations (7-9). While exercise has enhanced quality of life in breast cancer patients (4), overall nutritional needs and the metabolic benefits of exercise are unclear in this patient group. Understanding the effects of nutrition and exercise interventions in breast cancer patients will form the basis for future studies and programs that integrate nutrition, exercise, and metabolism to reduce cancer recurrence and other morbidities in survivorship. This study will examine the effects of nutrition and exercise intervention on body composition and metabolism in recently diagnosed breast cancer patients.
Subjects will receive an acute administration of pyridostigmine bromide, calculated on their body weight at clinical exam (1 mg/kg, 60mg max starting dose), and will be monitored for 2 hours post administration. Subjects will also receive a pre- and post-administration single-fiber EMG, respiratory tests and strength tests in order to evaluate the function of the neuromuscular junction. All study subjects will be enrolled in this arm.
Hepato-pancreato-biliary (HPB) emergencies in patients with cancer encompass an extensive array of various conditions, including primary malignancies that require prompt treatment, associated severe complications, and life-threatening consequences arising from treatment. In patients with cancer, the liver can be affected by chemotherapy-induced hepatotoxicity, veno-occlusive disease, Budd-Chiari syndrome, liver hemorrhage, and other complications arising from cancer therapy with all these complications requiring timely diagnosis and prompt treament. Cholecystitis induced by systemic anticancer therapies can result in severe conquences if not promptly identified and treated. The application of immunotherapy in cancer therapy is associated with cholangitis. Hemobilia, often caused by medical interventions, may require arterial embolization in patients with severe bleeding and hemodynamic instability. Malignant biliary obstruction in patients with biliary cancers may necessitate palliative strategies such as biliary stenting. In pancreatic cancer, patients often miss surgical treatment due to advanced disease stages or distant metastases, leading to potential emergencies at different treatment phases. This comprehensive review underscores the complexities of diagnostic and treatment roles of medical imaging in managing HPB emergencies in patients with cancer. It illustrates the crucial role of imaging techniques, including magnetic resonance imaging, computed tomography and ultrasound, in diagnosing and managing these conditions for timely intervention. It provides essential insights into the critical nature of early diagnosis and intervention in cancer-related HPB emergencies, ultimately impacting patient outcomes and survival rates.
BACKGROUND: Disturbed flow generates oscillatory shear stress (OSS), which in turn leads to endothelial inflammation and atherosclerosis. Piezo1, a biomechanical force sensor, plays a crucial role in the cardiovascular system. However, the specific role of Piezo1 in atherosclerosis remains to be fully elucidated.
METHODS AND RESULTS: We detected the expression of Piezo1 in atherosclerotic mice and endothelial cells from regions with disturbed blood flow. The pharmacological inhibitor Piezo1 inhibitor (GsMTx4) was used to evaluate the impact of Piezo1 on plaque progression and endothelial inflammation. We examined Piezo1's direct response to OSS in vitro and its effects on endothelial inflammation. Furthermore, mechanistic studies were conducted to explore the potential molecular cascade through which Piezo1 mediates endothelial inflammation in response to OSS. Our findings revealed the upregulation of Piezo1 in apoE-/- (apolipoprotein E) atherosclerotic mice, which is associated with disturbed flow. Treatment with GsMTx4 not only delayed plaque progression but also mitigated endothelial inflammation in both chronic and disturbed flow-induced atherosclerosis. Piezo1 was shown to facilitate calcium ions (Ca2+) influx in response to OSS, thereby activating endothelial inflammation. This inflammatory response was attenuated in the absence of Piezo1. Additionally, we identified that under OSS, Piezo1 activates the Ca2+/CaM/CaMKII (calmodulin/calmodulin-dependent protein kinases Ⅱ) pathways, which subsequently stimulate downstream kinases FAK (focal adhesion kinase) and Src. This leads to the activation of the OSS-sensitive YAP (yes-associated protein), ultimately triggering endothelial inflammation.
CONCLUSIONS: Our study highlights the key role of Piezo1 in atherosclerotic endothelial inflammation, proposing the Piezo1-Ca2+/CaM/CaMKII-FAK/Src-YAP axis as a previously unknown endothelial mechanotransduction pathway. Piezo1 is expected to become a potential therapeutic target for atherosclerosis and cardiovascular diseases.
The no-reflow phenomenon is one of the most common causes of adverse cardiovascular events in patients with ST-elevated myocardial infarction (STEMI). Re-canalization of infarct related arterial (IRA) flow related to better ventricular performance and lower mortality rate in patients with STEMI. In addition, no-reflow phenomena may limit the benefits of re-canalization of the IRA.

In recent years, many mechanical or pharmacological treatment strategies including adjunctive administration of glycoprotein IIb/IIIa inhibitors (GPI) have been proposed in patients with STEMI. Although current guidelines recommend that small molecule GPI should be administered as an upstream bolus followed by a continuous infusion in patients with STEMI, changes in clinical practice may obviate the need for GPI dosage or routes in current practice. Previous studies have shown that intravenous and intracoronary administration of GPI improve the prognosis and significantly reduce mortality in patients with STEMI. Recently, the Ongoing Tirofiban in Myocardial infarction Evaluation-2 (ON-TIME 2) trial found that the use of tirofiban started during the pre-hospital phase as upstream therapy for primary percutaneous coronary intervention (PCI) and continued for up to 18 hours infusion after the procedure showed an improvement in the markers of reperfusion. Additionally, a reduction was demonstrated in the death in recurrent myocardial infarction in urgent target vessel revascularization and thrombotic bailout. However, in the current literature there are insufficient data regarding the role of intracoronary administration of GPI inhibitors in patients with STEMI who developed the no-reflow phenomenon. The goal of this study was to evaluate the acute effect of intracoronary administration of tirofiban on no-reflow phenomenon in patients with STEMI and occurrence of no-reflow phenomenon undergoing primary PCI.
The recommended dose of Fludeoxyglucose F 18 Injection for an adult (70 kg) is 185-370 MBq (5-10 mCi), as an intravenous injection for studies of malignancy, cardiology, and epilepsy.

In general, Fludeoxyglucose F 18 Injection should be administered after patients have fasted for 4-6 hours. For cardiac use, Fludeoxyglucose F 18 Injection may be administered either to patients who have fasted or to patients who have received a glucose load (See Patient Preparation section).

The optimum rates of administration and upper safe dose for Fludeoxyglucose F 18 Injection have not been established. The time interval between doses of Fludeoxyglucose F 18 Injection should be long enough to allow substantial decay (physical and biological) of previous administrations.

The final dose for the patient should be calculated using proper decay factors from the time of the end of synthesis (EOS), and measured by a suitable radioactivity calibration system before administration. See decay factors in Table 3.

Patient Preparation: Blood glucose levels should be stabilized before Fludeoxyglucose F 18 Injection is administered. In non-diabetic patients this may be accomplished by fasting 4-6 hours before Fludeoxyglucose F 18 Injection. Diabetic patients may need stabilization of blood glucose on the day preceding and on the day of administration of Fludeoxyglucose F 18 Injection.

For cardiac imaging, administration of Fludeoxyglucose F 18 Injection to fasting patients limits the accumulation of Fludeoxyglucose F 18 to ischemic myocardium. This may make localization of the ischemic region difficult because the surrounding myocardium will not be well visualized. Conversely, administration of Fludeoxyglucose F 18 Injection to patients who have received a glucose load (e.g., 50-75 grams, 1-2 hours before administration of Fludeoxyglucose F 18 Injection) allows the surrounding, non-ischemic myocardium to be seen and facilitates localization of ischemic areas.

Imaging: Optimally, it is recommended that positron emission tomography (PET) imaging be initiated within 40 minutes of administration of Fludeoxyglucose F 18 Injection.

Static emission scans are acquired 30-100 minutes from time of injection.
The taste of Kl prepns. is made acceptable by adding Aerosil (RTM), opt. with essential oils, and aromatic flavourants and mono- or di-saccharides. A mixt. of 30 g Acrosil 200, 20 ml peppermint oil, 20 dextrose, 30 g lactose and 40 g KI was ground to give a colourless, mobile, aromatic-smelling powder with a pleasant taste. Capsules were filled with this power so that each capsule contained 400 mg KI. KI is effective against chronic bronchitis, asthma and heart and vascular disorders, and has a strong mucolytic effect. The addn. of aerosil removes the unpleasant taste of the KI and prevents discolouration.