anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Cigarette smokers, who are motivated to quit smoking but who rate the inhalation aspects of smoking as important will be randomized to three groups: Group 1. Nicotine ENDS + nicotine patch; Group 2: Nicotine ENDS + placebo patch; Group 3: Placebo ENDS + Nicotine patch. Participants will initially receive 1 week of 21 mg nicotine (or placebo) skin patches while continuing to smoke their usual cigarettes ad lib, in order to assess responsiveness to Nicotine Replacement Therapy (NRT). Starting with week 2, participants will receive nicotine-containing (or placebo) ENDS devices (menthol or non-menthol versions in accordance with their baseline preference). They will also be instructed to substitute ENDS for as many cigarettes as possible in this week. The target quit-smoking date will occur at the beginning of week 3. Treatments will continue until week 8 post-quit, at which time participants will be instructed to reduce ENDS use over the next 4 weeks, at which time ENDS will no longer be dispensed. Subsequently, the nicotine patch dose will be gradually reduced according to standard weaning regimen from 21 mg/24 h to 14 mg/24 h for 2 weeks, and 7 mg/ 24 h for 2 weeks. All nicotine-based treatments will end at week 16 after the quit date.
Studies have highlighted oxidative damage in the inner ear as a critical pathological basis for sensorineural hearing loss, especially the presbycusis. Poly(ADP-ribose) polymerase-1 (PARP1) activation responds to oxidative stress-induced DNA damage with pro-repair and pro-death effects resembling two sides of the same coin. PARP1-related cell death, known as parthanatos, whose underlying mechanisms are attractive research hotspots but remain to be clarified. In this study, we observed that aged rats showed stria vascularis degeneration and oxidative damage, and PARP1-dependent cell death was prominent in age-related cochlear disorganization and dysfunction. Based on oxidative stress model of primary cultured stria marginal cells (MCs), we revealed that upregulated PARP1 and PAR (Poly(ADP-ribose)) polymers are responsible for MCs oxidative death with high mitochondrial permeability transition pore (mPTP) opening and mitochondrial membrane potential (MMP) collapse, while inhibition of PARP1 ameliorated the adverse outcomes. Importantly, the PARylation of apoptosis-inducing factor (AIF) is essential for its conformational change and translocation, which subsequently causes DNA break and cell death. Concretely, the interaction of PAR and truncated AIF (tAIF) is the mainstream in the parthanatos pathway. We also found that the effects of AIF cleavage and release were achieved through calpain activity and mPTP opening, both of which could be regulated by PARP1 via mediation of mitochondria Ca2+ concentration. In conclusion, the PAR-Ca2+-tAIF signaling pathway in parthanatos contributes to the oxidative stress damage observed in MCs. Targeting PAR-Ca2+-tAIF might be a potential therapeutic strategy for the early intervention of presbycusis and other oxidative stress-associated sensorineural deafness.
The use of femtosecond (FS) laser has become one of the most significant technological advancements in refractive surgery. A breakthrough FS laser-assisted myopic and myopic astigmatic correction procedure can now be performed using a prototype femtosecond system. This first all-in-one FS-laser system was designed to perform the refractive lenticule extraction (ReLEx) procedures, femtosecond lenticule extraction (FLEx) and small-incision lenticule extraction (SMILE). In FLEx, a corneal flap is created by the FS laser (similar to LASIK) and lifted, allowing lenticule removal. For SMILE, a truly without flap procedure, only a small-2-4mm- incision is made, through which the lenticule is removed.

Ocular surface disruption during corneal refractive surgery is commonly considered to be closely related to the development of dry eye. Multiple etiologies contribute to this ocular surface disruption, including the flap creation and stromal ablation involved in previous refractive surgery techniques. Corneal nerve damage has been considered the main cause of dry eye, due to disrupted afferent sensory nerves, reduced blink reflex, and increased tear evaporation leading to tear film instability. In addition, postoperative inflammatory mediator fluctuations are also a key factor related to ocular surface damage. Extensive research has described the effects of cytokines, chemokines and growth factors in modulating corneal wound healing, cell migration, and apoptosis on the ocular surface after refractive surgery.

For both FLEx and SMILE, stromal ablation has been replaced by refractive lenticule removal. In terms of corneal flap formation, FLEx still requires an epithelial-stromal flap, while SMILE employs only a small incision to extract the lenticule. Hence, the investigators hypothesize that SMILE will have less effect on patients' ocular surface markers and inflammatory mediators, compared to FLEx. In support of this hypothesis, previous studies have reported that more damage to the sub-basal nerve plexus of the cornea and more changes in ocular surface evaluations were found after FLEx than after SMILE. In this study, the investigators have focused on postoperative changes to tear inflammatory mediators and the relationship of FLEx and SMILE to dry eye.
Drug safety trials require substantial ECG labelling like, in thorough QT studies, measurements of the QT interval, whose prolongation is a biomarker of proarrhythmic risk. The traditional method of manually measuring the QT interval is time-consuming and error-prone. Studies have demonstrated the potential of deep learning (DL)-based methods to automate this task but expert validation of these computerized measurements remains of paramount importance, particularly for abnormal ECG recordings. In this paper, we propose a highly automated framework that combines such a DL-based QT estimator with human expertise. The framework consists of 3 key components: (1) automated QT measurement with uncertainty quantification (2) expert review of a few DL-based measurements, mostly those with high model uncertainty and (3) recalibration of the unreviewed measurements based on the expert-validated data. We assess its effectiveness on 3 drug safety trials and show that it can significantly reduce effort required for ECG labelling-in our experiments only 10% of the data were reviewed per trial-while maintaining high levels of QT accuracy. Our study thus demonstrates the possibility of productive human-machine collaboration in ECG analysis without any compromise on the reliability of subsequent clinical interpretations.
MyStar DoseCoach - Device-supported treat-to-target regimen. Insulin glargine is administered subcutaneously on top of potential background therapy using oral anti-diabetic drug(s) or GLP1 RA injectable antihyperglycemic drug(s).
BACKGROUND: Dravet syndrome is a severe epilepsy disorder characterized by drug-resistant seizures and cognitive dysfunction, often caused by SCN1A gene mutations. It leads to neurodevelopmental delays and motor, behavioral, and cognitive impairments, with a high mortality rate. Treatment options include sodium valproate, clobazam, and newer agents such as cannabidiol and fenfluramine. Zonisamide, which is used in some cases, can cause hyperthermia and oligohydrosis. Herein, we present a case of a patient with Dravet syndrome whose seizures were controlled by treating infections and switching from zonisamide to perampanel.
CASE PRESENTATION: A 24-year-old Japanese man with Dravet syndrome presented to our department with aspiration pneumonia. The patient had been treated with valproate, sodium bromide, and zonisamide for a long time. His seizures were triggered by hyperthermia. The patient was experiencing a sustained pattern of hyperthermia caused by infection, zonisamide, and persistent convulsions, which caused a vicious cycle of further seizures. In this case, the control of infection and switching from zonisamide to perampanel improved seizure frequency.
CONCLUSION: Dravet syndrome usually begins with generalized clonic seizures in its infancy because of fever and progresses to various seizure types, often triggered by fever or seizure-induced heat due to mutations in the SCN1A gene that increases neuronal excitability. Seizures usually diminish with age, but the heat sensitivity remains. In this case, seizures were increased by repeated infections, and hyperthermia was induced by zonisamide, resulting in status epilepticus. Perampanel, an aminomethylphosphonic acid receptor antagonist, decreased seizures but caused psychiatric symptoms. It was effective in suppressing seizures of Dravet syndrome in this patient.
Hypertension (HTN) is the most prevalent modifiable risk factor for cardiovascular disease among U.S. adults. Despite a long history of established guidelines to support clinical management, only half of U.S. adults diagnosed with HTN have poorly controlled blood pressure (BP) and medication adherence to proven effective treatment remains suboptimal. Clinical decision support (CDS) has the potential to overcome barriers to delivering guideline-recommended care and improve HTN management. However, optimal strategies for scaling CDS have not been well established, particularly in small independent primary care practices which often lack the resources to effectively change practice routines in order to effectively utilize CDS. Further, CDS is used in relatively few components of the medication management process, despite indications that CDS alerts are likely to impact patient care. Practice facilitation is a well-demonstrated implementation strategy to support process changes and has the potential to facilitate CDS implementation. Our objective is to rigorously evaluate whether practice facilitation provided in concert with a HTN-focused CDS that incorporates medication adherence results is an effective strategy for scaling and implementing CDS. The investigators will initially update and incorporate an evidence-based hypertension-focused CDS shown to be effective in Federally Qualified Health Centers (FQHCs) into an existing commercial electronic health record (EHR) system used by a large network of independent primary care practices. This CDS will employ several features shown to be effective in the FQHCs, including passive alerts, order sets, documentation templates, standardized medication adherence questionnaires, and clinical reminders. Additionally, the CDS will incorporate a new feature, a medication adherence alert based on prescription claims data. The investigators will then randomize 40 small independent primary care practices in New York City to receive either practice facilitation in addition to the CDS or the CDS alone. The PF intervention will include an initial training in the CDS and review of current guidelines along with follow-up in-person and remote meetings for coaching and supporting integration into the workflow. After a twelve-month intervention period, The investigators will examine the differences in blood pressure control achieved by practices in the CDS plus practice facilitation group versus practices that received the CDS alone. The investigators will also assess the implementation process for scaling the CDS using the RE-AIM framework. The results of this study will inform future efforts to implement and scale CDS into small primary care practices, where much of care delivery occurs in the U.S.
BACKGROUND: Aronia melanocarpa is nowadays valued for its high content of biologically active substances, the main group of which are polyphenols, which include anthocyanins, flavonols, flavanols, proanthocyanidins and phenolic acids. From the available sources, we can conclude that extracts and juices from black chokeberry have a great potential in human nutrition and influence on their health.
OBJECTIVE: The research was to evaluate the effect of regular consumption of 100% organic chokeberry juice on selected anthropometric and lipid parameters of overweight or obese women.
MATERIAL AND METHODS: A clinical study consisted of 19 women with overweight and obesity, age from 44 to 63. The probands consumed 50 ml of chokeberry juice daily for 8 weeks as part of their regular diet. Body composition and biochemical indicators were monitored before consumption, after 4 and 8 weeks of nutritional intervention. Body composition was determined using multifrequency bioelectrical impedance analysis (MFBIA) - InBody 720. Biochemical analyzes of blood serum were performed using standard methods in an accredited laboratory using automatic biochemical analyzer a BioMajesty JCA-BM6010/C.
RESULTS: The monitored group of probands is characterized by menopausale and postmenopausale women, overweight or obese women with hypercholesterolemia without pharmacological treatment. Statistically significant differences (p<0.05) were observed when evaluating the amount of body fat (BFM) of the probands before the start of consumption and after the consumption of chokeberry juice. We noted a statistically significant reduction especially in the assessment of visceral fat (VFA) (p<0.001). There were no fundamentally significant changes in the lipid profile of women in this intervention study. With short-term consumption of chokeberry juice (after 4 weeks), we recorded an average reduction in total cholesterol and LDL-cholesterol, but without statistical significant. We also focused on the evaluation of the inflammatory marker CRP and noted a significant beneficial reduction of CRP (p˂0.05).
CONCLUSIONS: In the research, we evaluated the effect of 8 weeks consumption of 100% chokeberry juice on selected anthropometric parameters, focusing on changes in visceral fat and total fat in overweight and obese women. In conclusion, we can state that the regular consumption of chokeberry juice has a beneficial effect on fat tissue in women of reproductive age, which can reduce the risk of cardiovascular diseases.
OBJECTIVE: Paroxysmal non-epileptic events (PNEs) are a group of disorders that may be misdiagnosed as epilepsy. This study has aimed to assess the knowledge and practices of family physicians and pediatricians regarding the diagnosis, treatment, and follow-up of PNEs in children.
METHODS: The study was designed as a prospective cross-sectional study that was conducted between March 1, 2022, and June 1, 2022, by reaching pediatric specialists and assistants, family physicians, subspecialty assistants, and subspecialists using a Google questionnaire. The survey consists of 26 questions. The questionnaire used by the researchers was prepared in accordance with the literature search and it included detailed questions on the diagnosis, treatment, and differential diagnosis of PNEs.
RESULTS: A total of 37.3% worked as specialists. Most of the participants (41.3%) have worked in training and research hospitals, and 44.3% have been physicians for 6-10 years. The mean and standard deviation for the total score were 10.1 ± 2.6. The scores of family physicians were statistically lower than those of specialists, subspecialty assistants, and subspecialists. A total of 67.2% left the decision of whether the patient should stop taking their medication to another clinician. 45% of the doctors said that they were uncomfortable with the diagnosis.
SIGNIFICANCE: The study findings emphasized the significant knowledge gap among healthcare providers regarding PNEs in children, highlighting the need for targeted educational interventions to improve their understanding and diagnostic skills in this area.
Chronic myelomonocytic leukemia (CMML) is a severe myeloid malignancy affecting the elderly, for which therapeutic options are limited. DNA hypomethylating agents (HMAs) provide transient responses, failing to eradicate the malignant clone. Hematopoietic stem cell (HSC) aging involves heterochromatin reorganization, evidenced by alterations in histone marks H3K9me2 and H3K9me3. These repressive marks together with DNA methylation are essential for suppressing transposable elements (TEs). In solid cancers, the antitumor efficacy of HMAs involves the derepression of TEs, mimicking a state of viral infection. In this study, we demonstrate a significant disorganization of heterochromatin in CMML HSCs and progenitors (HSPCs) characterized by an increase in the repressive mark H3K9me2, mainly at the level of TEs, and a repression of immune and age-associated transcripts. Combining HMAs with G9A/GLP H3K9me2 methyltransferase inhibitors reactivates these pathways, selectively targeting mutated cells while preserving wild-type HSCs, thus offering new therapeutic avenues for this severe myeloid malignancy.
Childhood obesity has become a major non-communicable disease worldwide. It is associated with an increased risk of cardiometabolic factors, including diabetes and hypertension (HTN). The purpose of this study was to evaluate the association between obesity and HTN among Iranian children and adolescents. Cross-sectional data from the SHED LIGHT study performed in Tehran urban area were used in this report. The anthropometric values and blood pressure were analyzed. The obesity status was identified based on body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR). The blood pressure status was defined using percentiles for height, age, and sex. A total of 14,641 children with a mean age of 12.28 ± 3.1 years (6-18) were assessed, and 52.8% of them were boys. The prevalence of HTN was higher among obese compared to healthy weight subjects (p < 0.001). HTN had the strongest association with the central obesity by WC (odds ratio [OR] 4.098, 95% confidence interval [CI] 3.549-4.732), generalized obesity by BMI (OR 3.000, 95% CI 2.749-3.274), and central obesity by WHtR (OR 2.683, 95% CI 2.451-2.936). Moreover, parental university education, having studied in private schools, and the smaller number of household children increased the risk of obesity. The rate of HTN was high among children and adolescents with generalized and central obesities. HTN, elevated blood pressure, boy gender, and socioeconomic status were associated with obesity, emphasizing on the importance of screening and implementing lifestyle changes to decrease future risk of cardiovascular diseases.
Placebo orally for up to 12 weeks in the double-blind treatment period. Participants who completed double-blind treatment had the option of crossing over to lenalidomide 10mg in the open-label extension period for as long as benefit was derived from the drug or until study closure.
ALIMTA, oxaliplatin, and 5-fluorouracil (alone or with leucovorin) have shown activity as single agents in the treatment of colorectal cancer. Their different mechanisms of action make the combination of ALIMTA with oxaliplatin attractive as potential first-line therapies in terms of improving response rates and overall survival in patients with metastatic colorectal cancer. Current reports of the combination of oxaliplatin and 5-FU as first-line therapies suggest that there may be advantages in combining oxaliplatin with other antifolates in the treatment of colorectal cancer. ALIMTA is an attractive candidate to replace other drugs such as 5-FU in the combinations with oxaliplatin in the treatment of locally advanced and metastatic colorectal cancer. ALIMTA has potential advantages over 5-FU when combined with oxaliplatin because it requires a single short injection and inhibits multiple targets in the folate pathway. Therefore, we propose to conduct a trial reporting the clinical effectiveness and side effects of ALIMTA plus oxaliplatin and one of the current standards of care, the FOLFOX 4 regimen (Oxaliplatin plus 5-Fluorouracil and Leucovorin).
Liquid-liquid phase separation (LLPS) facilitates the formation of membraneless organelles within cells, with implications in various biological processes and disease states. AT-rich interactive domain-containing protein 1A (ARID1A) is a chromatin remodeling factor frequently associated with cancer mutations, yet its functional mechanism remains largely unknown. Here, we find that ARID1A harbors a prion-like domain (PrLD), which facilitates the formation of liquid condensates through PrLD-mediated LLPS. The nuclear condensates formed by ARID1A LLPS are significantly elevated in Ewing's sarcoma patient specimen. Disruption of ARID1A LLPS results in diminished proliferative and invasive abilities in Ewing's sarcoma cells. Through genome-wide chromatin structure and transcription profiling, we identify that the ARID1A condensate localizes to EWS/FLI1 target enhancers and induces long-range chromatin architectural changes by forming functional chromatin remodeling hubs at oncogenic target genes. Collectively, our findings demonstrate that ARID1A promotes oncogenic potential through PrLD-mediated LLPS, offering a potential therapeutic approach for treating Ewing's sarcoma.
Disclosed are a novel hepatitis A vaccine virus strain SH, a method for isolating the same, and a method for adapting the same to MRC-5 cells. The virus was isolated from the feces of a patient with an acute infection of hepatitis A and then transmitted to human diploid MRC-5 cells for adapted culture. In the adaptation process, the culture period for the early generation subculture was 35 days, and the culture period after the eighth passage was shortened to 24 days. With eight further passages, the antigen titer reached 1:512-1:1024, and the virus infectious titer reached 7.0-8.0lgCCID 50 /ml. Immunogenicity and cross protection assays showed that the hepatitis A inactivated vaccine produced from the virus strain has a good protective effect of immunogenicity. The virus strain is an ideal strain for the large-scale industrial production of hepatitis A inactivated vaccine.
FIELD: medicine.SUBSTANCE: invention relates to obstetrics and gynecology, namely to ultrasonic diagnostics in obstetrics and gynecology, and can be used for echogasterosalpingography using SonoVue ultrasound contrast agent. An observational transvaginal ultrasonography of the pelvic organs is performed in 2D/4D modes. A Cusco disposable gynecologic mirror with a fixator and soft 6600 Angiotech 5Fr balloon catheter are placed. Echo-negative and echo-negative contrast solutions are gradually introduced into uterine cavity. First, 0.9 % sodium chloride is introduced into uterine cavity. At that, the free passability of the uterine tube/tubes is indicated by: accumulation of the contrast medium in the periurovial space, air bubbles, turbulent fluid motion in projection of fimbrial part of uterine tube, appearance of free fluid in posteromatous space. That is followed by administering a contrast preparation in concentration of 2.5 mg in terms of a dry active substance dissolved in 5.0 ml of sodium chloride 0.9 %. If a passage of contrast is determined by fallopian tubes and visualization in perivarian spaces, a conclusion is made on one- or two-sided patency of the fallopian tubes. If the passage of contrast in the fallopian tubes, its presence in the perivarian spaces is not determined, then one or both uterine tube/tubes are stated to be obstructed.EFFECT: method provides visualization and analysis of tubal ligament state when assessing their passability with using a contrast preparation by using the SonoVue ultrasound contrast agent.1 cl, 6 dwg, 2 ex