anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The lack of innovative treatments in Alzheimer' disease (AD) is due to the non-understanding of the pathological process. The investigators need to include the latest concept of the sleep-wake/circadian kinetics of proteins in the brain, the new theory of the wash-out of pathological proteins via the brain glymphatic system during sleep and act at an early stage. New pathways are opened to better understand proteinopathies' processes and to propose new therapeutics interventions. The variations of the production/clearance curves of amyloid in the cerebrospinal fluid (CSF) during circadian rhythms and sleep-wake cycles have been demonstrated in in vivo metabolism experimentations. Suprachiasmatic nucleus damages due to AD may induce circadian regulation dysfunction and secondary sleep/wake cycle alterations. Key sleep/wake cycle neuromediators (Orexin-A, melatonin) are involved in the regulation of brain amyloid levels. The influence of orexin-A signaling on Aβ metabolism in animals and humans was recently highlighted. In rats, orexin-A release shows a 24-h fluctuation similar to that of brain interstitial fluid Aβ. In transgenic mice that overexpress amyloid precursor protein (APP), brain interstitial fluid Aβ concentration increases during wakefulness and after orexin-A infusion. Conversely, it decreases during sleep and after infusion of an orexin-A receptor antagonist6. In transgenic mice that overexpress APP/presenilin1 (PS1), in which the orexin gene is knocked out, a reduction of Aβ pathology was found, possibly caused by changes in sleep time. Orexin-A is linked to Aβ42 in AD and an increase of CSF orexin-A is observed in AD vs. controls, possibly related to sleep deterioration and neurodegeneration.

The narcolepy with cataplexy type 1 is the only disease with a specific orexin deficiency. Montpellier team have previously underlined in 15 patients with narcolepsy type 1 a normal level of Aβ42 in the CSF. The clinical expertise of the narcolepsy center suggested that the frequency of AD in old narcoleptic patients is low. The hypothesis was that patients with narcolepsy type 1 may be protected from amyloid brain lesions, hallmarks of the Alzheimer's process. The objective was to determine whether the brain amyloid load by PET-scan18 F-AV-45 measured with a semi-quantitative analysis (mean cortical SuVr) is lower in patients with narcolepsy type 1 older than 65 years-old than in cognitively normal age- and gender-matched controls.
BACKGROUND & AIMS: Both metabolic dysfunction and alcohol consumption cause steatotic liver disease (SLD). The distinction between metabolic dysfunction-associated SLD (MASLD) and MetALD categories is based on arbitrary thresholds of alcohol intake. Thus, we assessed the impact of different levels of alcohol consumption on SLD severity and their interaction with metabolic comorbidities.
METHODS: We performed a population-based study with transient elastography (FibroScan®) data from participants in Spain (derivation cohort) and the US (validation cohort). A controlled attenuation parameter ≥275 dB/m was used to define SLD. At least one cardiometabolic risk factor was required to define MASLD. Among patients with MASLD, low alcohol consumption was defined as an average of 5-9 drinks/week, moderate consumption as 10-13 drinks/week for females and 10-20 drinks/week for males, and increased alcohol intake (MetALD) as 14-35 drinks/week for females and 21-42 drinks/week for males. Significant fibrosis was defined as a liver stiffness measurement ≥8 kPa and at-risk metabolic dysfunction-associated steatohepatitis (MASH) as a FAST score ≥0.35.
RESULTS: The derivation cohort included 2,227 individuals with MASLD (9% reported low, 14% moderate alcohol consumption) and 76 cases with MetALD. Overall prevalences of significant fibrosis and at-risk MASH were 7.6% and 14.8%, respectively. In the multivariable analysis, alcohol consumption was independently associated with significant fibrosis and at-risk MASH. A dose-dependent increase in the prevalence of significant fibrosis and at-risk MASH was observed between the number of drinks/week and the number of cardiometabolic factors. The validation cohort included 1,732 participants with MASLD, of whom 17% had significant fibrosis and 13% at-risk MASH. This cohort validated the association between moderate intake and MASLD at risk of progression (odds ratio 1.69, 95% CI 1.06-2.71).
CONCLUSIONS: Moderate alcohol intake is commonly seen in MASLD and increases the risk of advanced disease to a level similar to that observed in MetALD.
IMPACT AND IMPLICATIONS: Metabolic risk factors such as overweight, diabetes or dyslipidemia, and alcohol consumption can cause liver disease. These factors frequently coexist, but their joint effects on liver fibrosis remain uncertain. In this study, we have analyzed individuals from the general population with MASLD (metabolic dysfunction-associated steatotic liver disease) enrolled in Spain and the US. We show that moderate alcohol consumption has a supra-additive effect with metabolic risk factors, exponentially increasing the risk of liver fibrosis. These results suggest that there are no safe limits of daily alcohol intake in patients with unhealthy metabolic status and MASLD.
Galantamine titration will be performed as described above. Memantine titration will be performed over 4 weeks in steps of 5 mg/day up to 20mg/day (10 mg b.i.d.). 50 % of this group will receive galantamine first, 50 % of the group will receive memantine first to allow for differential qualitative evaluation of tolerability of a combination therapy.
Arm A includes 14 patients. In treatment period 1, arm A receives standard PDF with the interventional drug alanyl-glutamine-dipeptide as add-on. As it is a cross-over study design, in treatment period 2, group A receives standard PDF without add-on.
The present invention includes methods for rational drug design. One exemplary method disclosed herein teaches the preparation of a highly specific affector of a first enzyme when the first enzyme is a member of a class of enzymes having a conserved catalytic core with a plurality of invariant residues. This method comprises identifying a second enzyme that is a member of that class of enzymes and has a known affector. The affector can be an inhibitor or activator of the second enzyme. In the practise of the method, a first complex is formed between the second enzyme and the known affector and data is obtained regarding the three-dimensional coordinates of the invariant residues in the complex. These coordinates are used to form a template. A model is then generated in which the first enzyme is in a conformation with the invariant residues in substantially the same conformation as in the template. Changes in the variable residues of the catalytic core of the first enzyme are compared to the variable residues in the catalytic core of the second enzyme. The second enzyme is modified to include these non-conserved changes and an affector is designed using computer modelling that will induce a conformation on the catalytic core of the first enzyme in which the invariant residues are in substantially the same coordinates as the coordinates of the template when the first enzyme is formed as a second complex with the newly designed affector. The designed affector can be further refined to provide improved affector activity.
We herein report a rare case of hereditary diffuse gastric cancer in a Japanese man. A 41-year-old man underwent esophagogastroduodenoscopy which revealed a small gastric erosion. Biopsy specimens showed signet ring cell carcinoma, and endoscopic submucosal dissection was performed. The patient's elder sister had died of gastric cancer at 38 years old. Considering the family history, a genetic test was conducted and revealed a CDH1 germline mutation. Although no carcinomatous lesion was detected endoscopically, prophylactic total gastrectomy was performed. The resection specimen showed seven microlesions of signet ring cell carcinoma confined to the lamina propria mucosae.
PROBLEM TO BE SOLVED: To provide an additive, a food, a beverage, a seasoning, and a cosmetic product which each contains the fruit juice of prickly pear cactus. SOLUTION: This additive contains the fruit juice of the prickly pear cactus. The prickly pear cactus fruit juice contains rich vitamins, minerals, soluble dietary fibers, pectin, and the like. Thus, the additive prevents the increase of body weight even when the amount of food being taken is increased. The rich soluble fibers included in the prickly pear cactus fruit juice shortens the intestinal retention time of food, thereby regulating the functions of the intestines, preventing obese. The additive reduces the adipose tissue weight without increasing organ weight. The additive also reduces serum lipids by the pectin included in the cactus fruit juice. Instead of the fruit juice, powder obtained by pulverizing the fruit juice may be used.
Participants receive apalutamide PO QD on days 1-28. Courses repeat every 28 days for up to 52 weeks in the absence of disease progression or unacceptable toxicity.
The use of ventilatory support, including CPAP (Continuous Positive Airway Pressure), which is a mode of ventilation with continuous positive pressure, and BiPAP (Bilevel Positive Airway Pressure), which is a mode of ventilation with two levels of pressure, has seen a significant increase in indications in recent years. The indications have become more numerous and increasingly complex. Sleep-related respiratory disorders, including obstructive sleep apnea-hypopnea syndrome, central apnea syndrome, and alveolar hypoventilation, are the primary reasons for these indications. In pediatrics, numerous conditions contribute to sleep-related respiratory disorders: ENT malformations, genetic conditions, obesity, bronchopulmonary dysplasia, neuromuscular diseases, thoracic deformities, and storage diseases.

The non-use or insufficient use of ventilatory support leads to a lack of treatment for sleep-related respiratory disorders. In the absence of treatment, the consequences are neurocognitive, cardiovascular, and metabolic, resulting in high morbidity. Non-use or insufficient use is a cause of failure of ventilatory support. Neither the use nor the failure of ventilatory support is clearly defined. It is crucial to evaluate the use of ventilatory support in order to correct factors related to non-use or insufficient use and to prevent the negative consequences resulting from unaddressed sleep-related respiratory disorders. This pilot study aims to assess the use of ventilatory support at home in pediatrics through interviews with patients and their parents. We will use a questionnaire designed for the study, consisting of 10 questions regarding sleep, symptoms, quality of life, technical issues, side effects, economic barriers, and adherence, to describe their experiences with ventilatory support.
The current proposal seeks to evaluate an eight-session, computerized, anger-focused intervention for smokers (Anger Reduction Treatment or ART). The investigators will administer this intervention to smokers (N = 114) who are interested in quitting and have elevated levels of trait anger. Participants will be randomly assigned to receive either: (1) computerized ART, consisting of interpretation bias modification, or (2) a computerized control condition, which consists of health education and relaxing video clips. The computerized sessions (eight total) will take place twice a week for four weeks. All participants will have a scheduled quit date for the beginning of the third week of treatment (i.e., at mid-treatment). All participants will also receive nicotine patch therapy to use at their scheduled quit date. Anger symptoms, smoking cravings, and smoking frequency will be assessed throughout treatment. Smoking status, anger, and other measures of negative affect will also be assessed at baseline and regularly for 12-weeks following the scheduled quit date.

The investigators will test whether, compared to the control condition, the anger-reduction treatment will lead to: 1) greater reductions in anger and 2) greater abstinence rates at post-cessation and at follow-up assessments. The investigators will also test whether changes in anger-related symptoms account for group differences in abstinence rates.
Children with a molecularly confirmed diagnosis of Angelman Syndrome meeting the protocol requirements will be selected randomly. All participants will receive the study drug, minocycline, over an identical time course. Participants will undergo identical baseline, 8 and 16 week follow up assessments.
We will enroll 60 Group II PH (PH-HFpEF) or Group I PAH patients and 60 matched healthy controls over three years. The Subjects will receive a single dose of one of the two study drugs, determined by whether they will participate in one study visit or two: 15N nitrate (1,000 mg) or 14N Sodium Nitrate: standard sodium nitrate, and all will receive one dose of CLA 3g. Twenty of the PH or PAH subjects and 20 of the control subjects willing to return for a follow up visit 24 hours after drug administration will receive 15N nitrate. All others will receive standard sodium nitrate. CLA will be obtained from GNC (General Nutrition Corporation) and given once.

Throughout the experiment, we will measure blood pressure, heart rate, and respiratory rate as well as co-oximetry. Plasma samples are collected at approximate times 0, 2, and 6 hrs post-drug administration. Urine will be collected at approximate times 0 and 6 hrs. We will examine plasma and urine nitrate and nitrite. The 40 subjects who return for a second visit 24 hours post-drug administration will provide an additional plasma and urine sample.
In this study, the investigators are comparing healthy individuals to HIV and Fibromyalgia patients. The investigators are measuring the differences in pain processing between subject groups in the presence and absence of different music and distraction conditions. The investigators will be using Quantitative Sensory Testing (QST) in order to induce varying pain conditions on the participants. The investigators will also have participants complete sets of psychosocial questionnaires. Patients with Fibromyalgia tend to have a higher pain sensitivity. Additionally, patients with an HIV diagnosis tend to be prescribed opioid medications. The investigators would like to find out if music can modulate pain, and in turn help reduce the amount of opioid medications those with a chronic pain diagnosis take.
The heart failure patients in the intervention group were given web-based training for three months after discharge and followed up by telephone at the first, fourth, eighth and 12th weeks. At the same time, a text message was sent once a week. Scale data were collected before the patient was discharged from the hospital and at the third month of discharge.
Over 10 million Americans have osteoporosis, which is defined as a chronic, progressive disease presenting with deterioration of bone tissue and fragility subsequently leading to an increased fracture risk1. A positive diagnosis for osteoporosis is significantly correlated with increased age, making geriatrics patients an at-risk group for bone health complications2. A pathophysiological diagnosis for osteoporosis is done radiographically based on bone mineral density from a dual energy x-ray absorptiometry assessment (DXA)3. DXA scans have been used increasingly over time in geriatric populations to screen patients for osteoporosis4; however, one problem with DXA scans is the radiation dose due to x-ray radiography4. Therefore, using DXA scans as a preliminary screening method comes with risks, even though it is the gold standard for diagnosis3.

Osteoporosis is often referred to as a silent disease because people are not aware that they have low bone density9. The first sign may be loss of height but can also be a fracture due to a ground level mechanical fall. As people age, their bones lose their strength (density) and become more brittle2,10. Unfortunately, fractures can have devastating effects on people's quality of life causing chronic pain, difficulties with mobility, need for increased assistance, isolation, increased nursing home placement and rates of death10. Also, once a person has fallen and had a fragility fracture, they are likely to do so again10. Our goal is to encourage older adult patients to follow-up with their doctors to discuss osteoporosis screening, diagnosis, and treatment to help reduce the prevalence of fragility fractures.

Osteoporosis follow-up rates need to be improved in geriatric populations. Increased compliance with follow-ups and medication recommendations have been shown to decrease fracture rates in this population5. In-office patient measurements have been previously shown to increase compliance with treatment. In the case of smoking, carbon monoxide (CO) monitors increased a patient's willingness to comply with cessation protocols significantly in an orthopedic fracture population6.

Quantitative ultrasound scans (QUS) have emerged as a simple point-of-care test for bone density. 7 For a quantitative ultrasound scan, the patient sits in a chair and places their heel on specialized ultrasound machine in a manner similar to having the size of the foot measured at a department store. The machine is portable and can be performed at the bedside. Prior research has demonstrated that, although QUS cannot replace DXA scans as the gold standard for diagnosis of osteopenia, it can still be used to immediately identify abnormal bone density8. Integrating QUS scans into geriatric fracture treatment comes at little risk, and, similar to home CO monitoring for smoking cessation, may provide additional information to the patient to encourage further action.
Background/Objectives: Pectus excavatum (PEx) is considered, at least partially, a familial disorder. A variety of inheritance patterns, associations with genetic syndromes, and pathogenic variants have been reported. However, the etiology of this condition is still not completely understood, and no known genes have been identified as definitive contributors. Methods: Family members with a confirmed PEx diagnosis (one proband and two first-degree relatives) and non-affected members were recruited into this study. Exome sequencing was performed on all affected familial PEx cases to systematically screen for candidate genes that are likely to be causative for PEx, and on non-affected family members for variant segregation analysis. Results: Ten families, with three affected members each, participated, providing thirty familial PEx cases. Different inheritance patterns were represented across the ten pedigrees, with possible incomplete penetrance. Genetic variants in REST (essential for neuronal development and associated with pectus deformities in prior studies), SMAD4 (variants can predispose individuals to thoracic aortic diseases), and COL5A (associated with Ehlers-Danlos syndrome and Fibromuscular dysplasia) were initially identified as potentially linked to the development of pectus deformities and segregated with the phenotype. No variants were shared across families in the studied population. Conclusions: Germline exome sequencing of families with multiple individuals affected by PEx in our study identified potential gene candidates linked to PEx. These candidates are private to individual families and no strong candidates shared across multiple families were identified. These findings suggest that the inheritance of PEx may not be strongly related to a shared single genetic variant in known genes. Given the accumulating evidence for the genetic basis of familial PEx, further studies, including polygenic analyses, as well as assessment of the non-coding genome and possible epigenetic markers are warranted.
This is a phase I/II open-label study to determine the lowest safe, effective dose of budesonide given with calfactant as the vehicle; the investigators will perform an unblinded dose escalation study. The investigators will administer four dosing levels of budesonide suspended in calfactant beginning with 0.025 mg/kg of budesonide administered to 8 extremely low gestational age newborns (ELGANs) who are intubated at 3-10 days of age. Daily doses (at the same dosage) will be administered to infants who remain intubated for a potential of 5 total doses in each patient. Subsequent groups of 8 infants each will receive 0.05 mg/kg, 0.10 mg/kg, and 0.15 mg/kg of budesonide in calfactant (up to 5 total doses in each patient). A total of up to 32 infants will be enrolled in the trial. The investigators will evaluate the clinical, laboratory and safety data from each group of treated infants to 28 days of age before moving to the next dosing level of budesonide.
The precise and targeted delivery of therapeutic agents to the lesion sites remains a major challenge in treating brain diseases represented by ischemic stroke. Herein, we modified liposomes with mesenchymal stem cells (MSC) membrane to construct biomimetic liposomes, termed MSCsome. MSCsome (115.99 ± 4.03 nm) exhibited concentrated accumulation in the cerebral infarcted hemisphere of mice with cerebral ischemia-reperfusion injury, while showing uniform distribution in the two cerebral hemispheres of normal mice. Moreover, MSCsome exhibited high colocalization with damaged nerve cells in the infarcted hemisphere, highlighting its advantageous precise targeting capabilities over liposomes at both the tissue and cellular levels. Leveraging its superior targeting properties, MSCsome effectively delivered Dl-3-n-butylphthalide (NBP) to the injured hemisphere, making a single-dose (15 mg/kg) intravenous injection of NBP-encapsulated MSCsome facilitate the recovery of motor functions in model mice by improving the damaged microenvironment and suppressing neuroinflammation. This study underscores that the modification of the MSC membrane notably enhances the capacity of liposomes for precisely targeting the injured hemisphere, which is particularly crucial in treating cerebral ischemia-reperfusion injury.
Subjects received FOLFOX regimen HAIC treatment, within 2 weeks of regorafenib (28 days as a cycle, 80-160 mg qd regorafenib orally on days 1-21) and immune checkpoint inhibitors (continue treatment according to the original plan, 1 cycle every 3 weeks) treatment. HAIC treatment was repeated every 3 weeks for a maximum of six cycles.
INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a fatal neurogenerative disease with no effective treatment to date. Despite numerous clinical trials, the majority of studies have been futile in their effort to significantly alter the course of the disease. However, these studies may still provide valuable information for identifying patient subgroups and generating new hypotheses for future research. Additionally, synthesising evidence from these studies may help overcome the limitations of individual studies. Network meta-analysis may refine the assessment of efficacy in specific patient subgroups, evaluate intervention characteristics such as mode of administration or biological mechanisms of action, and rank order promising therapeutic areas of interest. Therefore, we aim to synthesise the available evidence from ALS clinical trials.
METHODS AND ANALYSIS: We will conduct a systematic review to identify all clinical trials that assessed disease-modifying pharmaceutical therapies, cell therapies, or supplements in patients with ALS. Outcomes of interest are clinical disease progression outcomes and survival. We will conduct this search in the period Q4 2024 in three databases: PubMed, Embase and ClinicalTrials.gov for studies from 1999 to 2023. Individual patient data and aggregate data will be collected and subsequentially synthesised in meta-analytical models. The final model will be presented as an open-source web application with biannual updates of the underlying data, thereby providing a 'living' overview of the ALS clinical trial landscape.
ETHICS AND DISSEMINATION: No ethics approvals are required. Findings will be presented at relevant conferences and submitted to peer-reviewed journals. Data will be stored anonymously in secure repositories.