anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The RAF family of kinases includes key activators of the pro-tumourigenic mitogen-activated protein kinase pathway. Hyperactivation of RAF proteins, particularly BRAF and CRAF, drives tumour progression and drug resistance in many types of cancer. Although BRAF is the most studied RAF protein, partially owing to its high mutation incidence in melanoma, the role of CRAF in tumourigenesis and drug resistance is becoming increasingly clinically relevant. Here, we summarize the main known regulatory mechanisms and gene alterations that contribute to CRAF activity, highlighting the different oncogenic roles of CRAF, and categorize RAF1 (CRAF) mutations according to the effect on kinase activity. Additionally, we emphasize the effect that CRAF alterations may have on drug resistance and how precision therapies could effectively target CRAF-dependent tumours. Here, we discuss preclinical and clinical findings that may lead to improved treatments for all types of oncogenic RAF1 alterations in cancer.
Based on a priori analysis the investigators will need 100 subjects in a placebo arm (normal saline) and 100 subjects in a treatment arm (3% sodium chloride), for a total of 200 patients. This study will be conducted on healthy subjects with normal renal function undergoing anterior cervical discectomy and fusion for degenerative indications only. Subjects will be randomized to the treatment or placebo arm (which will be double blinded). Subjects in the treatment arm will begin to receive intravenous 3% sodium chloride before the incision is made. The solution will be given at a rate of 10 cc/hour over a period of 24 hours. Baseline, post-operative, and delayed post-operative dysphagia surveys will be administered either in person or by telephone. The investigators hope to decrease the incidence and severity of post-operative dysphagia.
The gut microbiota is one of the most critical factors in human health. It involves numerous physiological processes impacting host health, mainly via immune system modulation. A balanced microbiome contributes to the gut's barrier function, preventing the invasion of pathogens and maintaining the integrity of the gut lining. Dysbiosis, or an imbalance in the gut microbiome's composition and function, disrupts essential processes and contributes to various diseases. This narrative review summarizes key findings related to the gut microbiota in modern multifactorial inflammatory conditions such as ulcerative colitis or Crohn's disease. It addresses the challenges posed by antibiotic-driven dysbiosis, particularly in the context of C. difficile infections, and the development of novel therapies like fecal microbiota transplantation and biotherapeutic drugs to combat these infections. An emphasis is given to restoration of the healthy gut microbiome through dietary interventions, probiotics, prebiotics, and novel approaches for managing gut-related diseases.
INTRODUCTION: Cervical dystonia (CD) causes involuntary movements and postures of the head, neck, and shoulders, as well as nonmotor symptoms including pain, mood, and sleep dysfunction, and impacts quality of life. The first-line treatment for CD is botulinum neurotoxin (BoNT) injections.
AREAS COVERED: The clinical presentation and diagnosis of CD, as well as where BoNT resides in the treatment landscape, is reviewed first. Next, the mechanism of action and the pharmacological differences in the available preparations of BoNT products are explained. The evidence base for motor and nonmotor efficacy and safety of the available BoNT formulations is reviewed, with attention to duration of benefit as a driver of patient satisfaction. Practical determinants of BoNT efficacy are reviewed including muscle selection, accurate muscle injection, factors related to poor or deteriorating response, and immunogenicity.
EXPERT OPINION: BoNT represents a significant advancement in the treatment of CD. More accurate diagnosis, muscle selection and targeting, and dosing can improve outcomes with existing BoNT formulations. Further refinement of BoNT potency, duration of action, safety, and immunogenicity will help reduce unmet needs in the magnitude and duration of benefit. Additional validation of DBS and MRI-guided focused ultrasound may expand options for patients with toxin nonresponse.
FIELD: medicine; prohylaxis of carries damage to teeth. SUBSTANCE: method includes combination of laser irradiation activating the protein matrix of tooth hard tissues and exchange and diffusion processes in them. After irradiation is performed mineral condensed compound is applied on tooth surface. Compound contains calcium and fluorine. Corse of prophylactic measured may be preformed by patient independently at home. Method precludes hazard of damaging the soft tissues of oral cavity. EFFECT: provision for optimal conditions for demineralization prophylaxis. 4 cl, 1 ex
Drug treatments for pain often do not outperform placebo, and a better understanding of placebo mechanisms is needed to improve treatment development and clinical practice. In a large-scale fMRI study (N = 392) with pre-registered analyses, we tested whether placebo analgesic treatment modulates nociceptive processes, and whether its effects generalize from conditioned to unconditioned pain modalities. Placebo treatment caused robust analgesia in conditioned thermal pain that generalized to unconditioned mechanical pain. However, placebo did not decrease pain-related fMRI activity in brain measures linked to nociceptive pain, including the Neurologic Pain Signature (NPS) and spinothalamic pathway regions, with strong support for null effects in Bayes Factor analyses. In addition, surprisingly, placebo increased activity in some spinothalamic regions for unconditioned mechanical pain. In contrast, placebo reduced activity in a neuromarker associated with higher-level contributions to pain, the Stimulus Intensity Independent Pain Signature (SIIPS), and affected activity in brain regions related to motivation and value, in both pain modalities. Individual differences in behavioral analgesia were correlated with neural changes in both modalities. Our results indicate that cognitive and affective processes primarily drive placebo analgesia, and show the potential of neuromarkers for separating treatment influences on nociception from influences on evaluative processes.
Chidamide, 20 mg,twice per week; Rituximab 375mg/m2, d1, intravenous drip; Gemcitabine 1000mg/m2, d2, intravenous drip; Oxaliplatin 100mg/m2, d2,intravenous drip; All patients received up to 6 treatment cycles of 21 days. Patients with CR or PR will receive chidamide maintenance therapy.
In each country, this arm constitute with 6 clusters where 2 from high, 2 from medium and 2 from low shadfly destiny. Each cluster has 50 households. It will receive IDWL intervention.
BACKGROUND: Chronic hepatitis-B virus (HBV) infection due to mother-to-child transmission (MTCT) during the perinatal period is an important global health concern. Chile is a low-prevalence country with an increasing migratory inflow from Latin- American countries, with intermediate to high endemic rates of HBV infection, and until 2021, there is no universal maternal screening. This study aimed to evaluate infant outcomes using a risk-based strategy of maternal screening to prevent MTCT of hepatitis B virus (HBV) in a low-prevalence country.
METHODS: This prospective study included infants born to HBsAg-positive women detected using a local risk-based strategy. The exposed infants received immunoprophylaxis (IP) and follow-up to evaluate their clinical outcomes and immune responses through post-serological vaccine testing (PSVT) after completing the three- dose schedule of the HBV vaccine.
RESULTS: A total of 99 HBsAg-positive mothers were detected. Seventy-six (82%) infants completed the follow-up and had PSVT between 9 and 12 months of age. 55.2% female, the median gestational age was 39 weeks (25-41) and the median birth weight was 3,130g (816-4,400 g). All patients received IP with recombinant HBV vaccine plus hepatitis-B virus immunoglobulin (HBIG) and three doses of the HBV vaccine. There were no cases of HBV infection, and 96% (72) responded to immunization with HBsAg antibodies (anti-HBsAg) >10 UI/ml, with a median level of 799 IU/ml.
CONCLUSIONS: A high-risk strategy can be implemented in countries with non-universal screening for VHB. Timely IP plus high-uptake VHB vaccination in infants born to HBsAg-positive mothers was associated with a high immunogenic response and absence of MTCT.
BACKGROUND: The study aimed to evaluate the prevalence and pattern of long COVID-19 (LC) symptoms among individuals who had contracted COVID-19, to calculate the incidence of LC, and to provide insights into risk factors associated with developing LC in this population.
METHODS: This population-based cross-sectional survey was conducted in Fars province in 2023. Adult participants with a history of COVID-19 were recruited using a cluster random sampling method, alongside a control group with similar characteristics through the same methodology. Data were collected through in-person interviews using two researcher-developed data collection forms focused on demographic and clinical information.
RESULTS: A total of 2010 participants, comprising 1561 (77.7%) and 449 (22.3%) individuals with and without a previous history of COVID-19 were included. Among those with COVID-19 history, the prevalence of experiencing any symptoms was 93.7% (95% CI of 92.3%-94.8%) during the disease acute phase and 36.4% (95% CI of 34.0%-38.8%) after recovery. The incidence of symptoms specifically related to COVID-19, calculated by comparing the symptom rates between participants with and without a history of COVID-19, was found to be 13%. Factors such as older age, previous hospitalization for COVID-19, presence of cardiovascular disease, and use of steroids/chemotherapy were associated with LC symptoms.
CONCLUSIONS: Our investigation sheds light on long-term aspects of COVID-19, demonstrating a significant prevalence of LC with diverse manifestations. It also underscores the importance of establishing standardized criteria and control groups in research on LC to address challenges related to heterogeneity and potential overestimation of symptoms.
The invention provides a protein peptide gene with excellent repairing effect, the effective nucleotide sequence of the gene is shown in SEQ ID NO. 1; the invention also provides an amino acid sequence of the active protein peptide (EL for short) coded by the active protein peptide gene with excellent repair function, which is shown in SEQ ID NO. 2. The invention grafts the gene segment of active protein peptide on the genetic information carrier by the in vitro gene protein recombination technology, transplants the gene segment into the gene engineering bacterium bacillus coli DH5a strain, prepares the active peptide protein of the invention by density fermentation, protein separation and purification, and freeze drying, and can ensure that the activity of the active peptide protein is not reduced in 3 years under the freeze-drying state. Cell experiments and human clinical test experiments prove that the protein peptide has excellent effects on the repair of the acne muscle and the repair after medical and artistic activities. The active peptide has high safety, and is effectively authenticated through microbial detection, heavy metal content detection, cell experiments and safety; the process is feasible after verification and can be used for batch production.
Whole-body imaging becomes increasingly important in oncologic patients not only for primary cancer staging, but also for assessment of response to therapy. So far, PET/CT is a key method to assess cancer-related changes of metabolism in tumors, which is crucial for response evaluation and to differentiate between benign and malignant lesions. Limitations of PET/CT include the assessment of sclerotic bone metastasis, which often do not show increased tracer uptake. Certain organ metastasis (especially in brain and liver) are also barely detectable due to physiologically increased uptake. Moreover, both CT and administration of radioactive tracer are associated with radiation exposure for patients. Whole-body MRI (wb-MRI) including functional techniques (e.g. Diffusion-weighted Imaging (DWI) to evaluate cell density) enables a functional staging and therapy assessment without use of ionizing radiation. Advantages to assess sclerotic bone lesions and organ metastases have been confirmed in recent literature. Limitations of MRI include detection of lesions in organs with high susceptibility and motion like the thorax.
Malignancies, including non-melanoma skin cancer (NMSC), were observed in clinical trials with CIBINQO for atopic dermatitis [see Adverse Reactions (6.1)].

Perform periodic skin examination for patients who are at increased risk for skin cancer. Exposure to sunlight and UV light should be limited by wearing protective clothing and using broad-spectrum sunscreen.

Malignancies, including lymphomas, have occurred in patients receiving JAK inhibitors used to treat inflammatory conditions. In a large, randomized, postmarketing safety trial of another JAK inhibitor in RA subjects, a higher rate of malignancies (excluding non-melanoma skin cancer (NMSC)) was observed in subjects treated with the JAK inhibitor compared to those treated with TNF blockers. CIBINQO is not approved for use in RA. A higher rate of lymphomas was observed in subjects treated with the JAK inhibitor compared to those treated with TNF blockers. A higher rate of lung cancers was observed in current or past smokers treated with the JAK inhibitor compared to those treated with TNF blockers. In this trial, current or past smokers had an additional increased risk of overall malignancies.

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with CIBINQO, particularly in patients with a known malignancy (other than a successfully treated NMSC), patients who develop a malignancy when on treatment, and patients who are current or past smokers.
Lumbar spinal stenosis is one of the most common causes of low back pain in the elderly and can lead to significant disability. The symptoms of spinal stenosis range from low back pain to neurogenic claudication with lower extremity pain, weakness and/or sensory changes related to activities. As spinal stenosis can affect the central canal as well as the lateral recesses and intervertebral foramen variably, symptoms can involve single or multiple myotomes and dermatomes. Since the causes of spinal stenosis are most frequently degenerative changes, the symptoms of spinal stenosis often, but not always, worsen over time. Despite the prevalence of spinal stenosis, treatment of spinal stenosis remains somewhat controversial. Common treatments include conservative measures such as non-steroidal anti-inflammatories (NSAIDS), activity modification and physical therapy as well as more invasive treatments such as epidural steroid injections and surgery. Although surgery has been demonstrated to provide some benefit to many individuals with spinal stenosis, ESI are being used with increasing frequency as a less invasive, potentially more cost effective and safer treatment for spinal stenosis. However, there is a lack of data to demonstrate the effectiveness and safety of epidural steroid injections for spinal stenosis, particularly in the older adults.

Because of the compelling need for effective therapy for patients suffering from spinal stenosis and because epidural steroid injections are rapidly becoming standard of care for treating these patients - even in the absence of compelling clinical evidence - we are conducting a randomized, controlled trial in order to test the hypothesis that lumbar epidural steroid injections improve functional status and pain associated with spinal stenosis. The main objective of the study is to conduct a blinded, randomized controlled trial (RCT) in elderly patients with spinal stenosis to test if the effectiveness of epidural steroid injections (ESI) plus local anesthetic (LA) is greater than LA alone.
This study investigates the relationship between Alzheimer's disease (AD) pathology, brain structure and function, as well as cognition in non-demented older adults. The goal is to develop a more complete understanding of the factors that lead to cognitive decline in the elderly and progression to AD. The investigators will enroll 200 cognitively intact adults between the ages of 60-85 years old from the UCI Alzheimer's Disease Research Center or directly from the local community. Study procedures will include: 1) PET amyloid scans with Amyvid™ radiotracer (florbetapir-F18) and PET tau scans with \[18F\]MK6240 radiotracer; 2) High-resolution structural, functional, and diffusion MRI; and 3) Cognitive examinations. The investigators will track cognitive outcomes through longitudinal monitoring. Amyloid imaging will only be conducted once in the study at baseline, and MRI and tau PET imaging will be at baseline and Year 1. The investigators aim to identify the best combination of tests for predicting longitudinal cognitive/clinical decline. The proposed study will significantly inform the understanding of cognitive decline in the aging brain and allow investigators to better define preclinical AD and make recommendations for future intervention trials.
Antimicrobial resistance (AMR) has become a major issue in global health. Despite progress in the reduction of under 5 mortality rates in recent decades, the proportion of neonatal deaths occurring within this age group has increased, with almost one quarter of all neonatal deaths occurring due to serious bacterial infection. Common bacteria causing neonatal sepsis are now exhibiting widespread resistance to several classes of antibiotics. There is an urgent need to discover new, effective treatments and re-evaluate existing therapeutic agents to treat infections potentially caused by multi-drug resistant (MDR) pathogens. Gram-negative bacteria (GNB) predominate as the cause of neonatal sepsis, and are increasingly associated with high rates of resistance to the currently recommended WHO empirical therapy regimen of ampicillin/penicillin and gentamicin. There is therefore a need to develop an updated empiric regimen with improved efficacy in the context of increasing MDR sepsis in neonates. New antimicrobials under development will be expensive once licensed, and there are currently virtually no planned trials to assess their efficacy in neonates in low- and middle-income countries (LMICs).

One potential strategy is utilising an existing off-patent (and therefore affordable) antibiotic available in intravenous and oral formulations - fosfomycin. Fosfomycin has a wide spectrum of activity against Gram-positive and Gram-negative bacteria causing neonatal sepsis. It is mainly used for resistant urinary tract infections in adults, but has licenced neonatal and paediatric doses in Europe (though dosing regimens vary between countries). Both oral and IV formulations are available. A large clinical trial to assess the efficacy of a fosfomycin plus an aminoglycoside combination (compared to the current WHO recommended ampicillin and gentamicin) is anticipated, including sites in Kenya. The ultimate aim is for fosfomycin to be included in the WHO Essential Medicines List for children (EMLc) and be available for use in developing countries, where rates of resistance to ampicillin and gentamicin have been estimated at over 40%. The first steps before this trial are to clarify the pharmacokinetics (PK) and safety profile of fosfomycin in neonates, as well as generating further information regarding local patterns of bacterial susceptibility to fosfomycin. The aim of this study is to fulfil both these steps. Fosfomycin (IV and oral) PK will be investigated among 60 babies admitted to hospital and being treated for presumed sepsis; administered alongside the standard antibiotics. Another 60 babies receiving standard treatment only (without PK sampling) will be monitored in the same way to compare adverse events. In the laboratory at CGMR-C, previously archived bacterial isolates will be tested for their sensitivity to fosfomycin.
Adults who have had obesity from childhood are at greater risk of obesity-related comorbidities compared to those who only develop obesity in adulthood. The main way of mitigating these risks in obesity is with weight loss, which has been shown to positively affect the cardiorespiratory fitness (CRF) and body composition of adults. However, it is unclear whether the response of these outcomes to weight loss may be influenced by age of obesity onset. The objective of our study was to investigate how age of obesity onset mitigates the responsiveness of CRF, muscle strength and body composition to modest weight loss. Measurements were conducted at baseline and 12 weeks. In total, 37 participants (childhood-onset = 19, adult-onset = 18) lost 3.7% ± 0.4% through aerobic exercise and diet. The YMCA cycle ergometer test (YMCA) and the 20-m shuttle run test (20MSR) were used to estimate CRF (mL kg-1  min-1 ) and a handgrip dynamometer was used to estimate muscle strength. Total body composition was assessed by dual-energy x-ray absorptiometry (DEXA). Overall, CRF and body composition improved (time effect: p < 0.05) after 12 weeks. There was no group-by-time interaction for YMCA, 20MSR, muscle strength and body composition variables. Therefore, the present study suggests that individuals with childhood-onset obesity and adult-onset obesity can improve their CRF and body composition similarly after mild weight loss.
Benazepril hydrochloride tablets are indicated for the treatment of hypertension. They may be used alone or in combination with thiazide diuretics.

In using benazepril hydrochloride tablets, consideration should be given to the fact that another angiotensin-converting enzyme inhibitor, captopril, has caused agranulocytosis, particularly in patients with renal impairment or collagen-vascular disease. Available data are insufficient to show that benazepril hydrochloride does not have a similar risk (see WARNINGS).

Black patients receiving ACE inhibitors have been reported to have a higher incidence of angioedema compared to nonblacks. It should also be noted that in controlled clinical trials ACE inhibitors have an effect on blood pressure that is less in black patients than in nonblacks.
The recommended dosage regimen consists of one loading dose administered by intravenous (IV) infusion (on Day 1), followed by four additional weekly loading doses administered by subcutaneous (SUBQ) injection (on Days 2, 8, 15, and 22). The maintenance dose starts on Day 29 and is then administered every 4 weeks by subcutaneous injection. Administer doses based on the patient's actual body weight, as shown in Table 1.

The dosing schedule is allowed to occasionally vary within 2 days of the scheduled administration day (except at Day 1 and Day 2). If this occurs, the subsequent dose should be administered according to the regular schedule.

Modification of the maintenance dose is required if the patient's body weight changes to become consistently greater than or lower than 100 kg during the course of therapy.
An antislip agent for socks is provided. The antislip agent for socks includes an acrylic acid based polymer, glycerin and a fatty acid dextrin. It is preferred that an amount of the fatty acid dextrin in the antislip agent for socks is in the range of 0.05 to 1 mass%. It is preferred that an amount of the acrylic acid based polymer in the antislip agent for socks is in the range of 0.01 to 10 mass%. It is preferred that an amount of the glycerin in the antislip agent for socks is in the range of 0.1 to 80 mass%. Further, in the antislip agent for socks, when the amount of the fatty acid dextrin is defined as A [mass%] and the amount of the acrylic acid based polymer is defined as B [mass%], the following relation is satisfied: 0.02 ≤ B/A ≤ 20.