anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The Comprehensive In-vitro Proarrhythmia Assay (CiPA) initiative aims to refine the assessment of drug-induced torsades de pointes (TdP) risk, utilizing computational models to predict cardiac drug toxicity. Despite advancements in machine learning applications for this purpose, the specific contribution of in-silico biomarkers to toxicity risk levels has yet to be thoroughly elucidated. This study addresses this gap by implementing explainable artificial intelligence (XAI) to illuminate the impact of individual biomarkers in drug toxicity prediction. We employed the Markov chain Monte Carlo method to generate a detailed dataset for 28 drugs, from which twelve in-silico biomarkers of 12 drugs were computed to train various machine learning models, including Artificial Neural Networks (ANN), Support Vector Machines (SVM), Random Forests (RF), XGBoost, K-Nearest Neighbors (KNN), and Radial Basis Function (RBF) networks. Our study's innovation is leveraging XAI, mainly through the SHAP (SHapley Additive exPlanations) method, to dissect and quantify the contributions of biomarkers across these models. Furthermore, the model performance was evaluated using the test set from 16 drugs. We found that the ANN model coupled with the eleven most influential in-silico biomarkers namely    dVm dt  repol  ,  dVm dt  max  , APD 90 , APD 50 , APD tri  , CaD 90 , CaD 50 , Ca tri  , Ca Diastole  , q I n w a r d , a n d q N e t  showed the highest classification performance among all classifiers with Area Under the Curve (AUC) scores of 0.92 for predicting high-risk, 0.83 for intermediate-risk, and 0.98 for low-risk drugs. We also found that the optimal in silico biomarkers selected based on SHAP analysis may be different for various classification models. However, we also found that the biomarker selection only sometimes improved the performance; therefore, evaluating various classifiers is still essential to obtain the desired classification performance. Our proposed method could provide a systematic way to assess the best classifier with the optimal in-silico biomarkers for predicting the TdP risk of drugs, thereby advancing the field of cardiac safety evaluations.
LIVALO may cause myopathy (muscle pain, tenderness, or weakness associated with elevated creatine kinase [CK]) and rhabdomyolysis. Acute kidney injury secondary to myoglobinuria and rare fatalities have occurred as a result of rhabdomyolysis in patients treated with statins, including LIVALO.

Risk Factors for Myopathy

Risk factors for myopathy include age 65 years or greater, uncontrolled hypothyroidism, renal impairment, concomitant use of certain drugs (including other lipid-lowering therapies), and higher LIVALO dosage [see Dosage and Administration (2.2), Drug Interactions (7), and Use in Specific Populations (8.5, 8.6)]. Dosages of LIVALO greater than 4 mg once daily were associated with an increased risk for severe myopathy in premarketing clinical studies. The maximum recommended dose of LIVALO is 4 mg once daily.

Steps to Prevent or Reduce the Risk of Myopathy and Rhabdomyolysis

LIVALO is contraindicated in patients taking cyclosporine and not recommended in patients taking gemfibrozil [see Contraindications (4) and Drug Interactions (7)]. There are LIVALO dosage restrictions for patients taking erythromycin or rifampin [see Dosage and Administration (2.4)]. The following drugs when used concomitantly with LIVALO may also increase the risk of myopathy and rhabdomyolysis: lipid-modifying dosages of niacin (>1grams/day), fibrates, and colchicine [see Drug Interactions (7)].

Discontinue LIVALO if markedly elevated CK levels occur or if myopathy is either diagnosed or suspected. Muscle symptoms and CK elevations may resolve if LIVALO is discontinued. Temporarily discontinue LIVALO in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis (e.g., sepsis; shock; severe hypovolemia; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; or uncontrolled epilepsy).

Inform patients of the risk of myopathy and rhabdomyolysis when starting or increasing the LIVALO dosage. Instruct patients to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever.
For 16 weeks, participants will be asked to carry a mobile phone and wear a wrist-worn device for measuring activity. Participants in this arm will be asked to provide limited self-report data via the phone.
Study drugs are administered intravenously on a 3-weekly schedule and given consecutively on the same day in the following sequence: trastuzumab, followed by pertuzumab, carboplatin, and docetaxel. Trastuzumab is given at an initial dose of 8 mg/kg, followed by 6 mg/kg; Perjeta® is given at an initial dose of 840 mg, followed by 420 mg. Carboplatin is administered at a dose of AUC6 (area under the plasma concentration-time curve) and docetaxel is given at 75 mg/m2.
BACKGROUND: Substantial focus has been placed on atrial fibrillation (AF) treatment and associated stroke prevention rather than preventing AF itself. We employed Mendelian randomization (MR) approach to examine the causal relationships between 50 modifiable risk factors (RFs) and AF.
METHODS: Instrumental variables for genetically predicted exposures were derived from corresponding genome-wide association studies (GWASs). Summary-level statistical data for AF were obtained from a GWAS meta-analysis (discovery dataset, N = 1,030,836) and FinnGen (validation dataset, N = 208,594). Univariable and multivariable MR analyses were performed, primarily using inverse variance weighted method with a series of robust sensitivity analyses.
RESULTS: Genetic predisposition to insomnia, daytime naps, apnea, smoking initiation, moderate to vigorous physical activity and obesity traits, including body mass index, waist-hip ratio, central and peripheral fat/fat-free mass, exhibited significant associations with an increased risk of AF. Coffee consumption and ApoB had suggestive increased risks. Hypertension (odds ratio (OR) 95% confidence interval (CI): 5.26 (4.42, 6.24)), heart failure (HF) (OR 95% CI, 4.77 (2.43, 9.37)) and coronary artery disease (CAD) (OR 95% CI: 1.20 (1.16, 1.24)) were strongly associated with AF, while college degree, higher education attachment and HDL levels were associated with a decreased AF risk. Reverse MR found a bidirectional relationship between genetically predicted AF and CAD, HF and ischemic stroke. Multivariable analysis further indicated that obesity-related traits, systolic blood pressure and lower HDL levels independently contributed to the development of AF.
CONCLUSIONS: This study identified several lifestyles and cardiometabolic factors that might be causally related to AF, underscoring the importance of a holistic approach to AF management and prevention.
FIELD: medicine, cardiology. SUBSTANCE: method involves intravenous drop administration of nitroglycerol and one of vasodilating prostaglandin, for example, prostenon simultaneously. Preparations were administrated up to therapeutic effect attainment. Method can be used for treatment of patients with progressing stress stenocardia and its complications prophylaxis. Method prevents patient resistance to nitrate action, decreases myocardium infarction risk degree development and stenocardia attack duration and accelerates patients recovery. EFFECT: enhanced effectiveness of method. 3 tbl
The participant will see fruit drinks with the nutrition claim "No Artificial Sweeteners" (task 1). They will see a snack with a text warning "WARNING: High in added sugar" (task 2).
PURPOSE: To obtain a peptide agent having high bioavailability and suitable for the application to rectum and vagina by forming a peptide supported on a polymeric carrier in the form of a drug together with a mixture of an absorbing medium, a protease inhibitor, an antibacterial substance and conventional carriers and adjuvants. CONSTITUTION: A biologically active peptide is supported on a polymeric carrier such as polyamino acid, agar or dextrin and formed together with an absorbing medium (e.g. a condensation product of an anionic amino acid or a hydrolyzed protein and a fatty acid), a protease inhibitor (e.g. aprotinin or EAC), an antibacterial substance (e.g. a preservative or a chemotherapeutic agent acting on anaerobic bacteria) and conventional carriers and adjuvants. The peptide is e.g. insulin, GnRH and its homologue, substance P and its derivative, partial sequence, other synthesized oligopeptide (e.g. thymus peptide) and biologically produced peptide (e.g. cyclosporin).
The BHT DSMD intervention strategies adapted Stanford DSMP in a spiritual context is used in this group. Participants in the FB group will participate in BHT DSMS, which includes a Health Sermon, a 6-session Health Bible Study with cooking demonstrations, the Stanford DSMP and a Diabetes Resource Seminar delivered by two trained church lay leaders.
The Covid-19 pandemic has highlighted an era in hearing health care that necessitates a comprehensive rethinking of audiology service delivery. There has been a significant increase in the number of individuals with hearing loss who seek information online. An estimated 430 million individuals worldwide suffer from hearing loss, including 11 million in the United Kingdom. The objective of this study was to identify National Health Service (NHS) audiology service social media posts and understand how they were used to communicate service changes within audiology departments at the onset of the Covid-19 pandemic. Facebook and Twitter posts relating to audiology were extracted over a six week period (March 23 to April 30 2020) from the United Kingdom. We manually filtered the posts to remove those not directly linked to NHS audiology service communication. The extracted data was then geospatially mapped, and themes of interest were identified via a manual review. We also calculated interactions (likes, shares, comments) per post to determine the posts' efficacy. A total of 981 Facebook and 291 Twitter posts were initially mined using our keywords, and following filtration, 174 posts related to NHS audiology change of service were included for analysis. The results were then analysed geographically, along with an assessment of the interactions and sentiment analysis within the included posts. NHS Trusts and Boards should consider incorporating and promoting social media to communicate service changes. Users would be notified of service modifications in real-time, and different modalities could be used (e.g. videos), resulting in a more efficient service.
The objective was to explore the efficacy of single-port laparoscopic percutaneous extraperitoneal closure using double-modified hernia needles with hydrodissection (SLPEC group) and two-port laparoscopic percutaneous extraperitoneal closure (TLPEC group) for the treatment of giant indirect inguinal hernias in children. We performed a retrospective review of all children with giant indirect inguinal hernias (inner ring orifice diameter ≥ 1.5 cm) who underwent laparoscopic high ligation of the hernia sac at FuJian Children's Hospital from January 2019 to December 2021. We collected data from the medical records of all the children and analysed their clinical characteristics and operation-related and follow-up information. Overall, this study included a cohort of 219 patients with isolated giant inguinal hernias who had complete clinical data and who had undergone laparoscopic high ligation of the hernia sac at our centre. All procedures were successfully performed for the 106 patients who underwent SLPEC and for the 113 patients who underwent TLPEC at our centre. There were no statistically significant differences in patient age, sex, body weight, follow-up time or the side of inguinal hernia between the SLPEC group and the TLPEC group (P = 0.123, 0.613, 0.121, 0.076 and 0.081, respectively). However, there were significant differences in the bleeding volume, visual analogue scale (VAS) score, and postoperative activity time between the two groups (P ≤ 0.001). The operation times in the TLPEC group were significantly longer than those in the SLPEC group (P = 0.048), but there were no significant differences in hospital length of stay or hospitalization costs between the two groups (P = 0.244 and 0.073, respectively). Incision scars were found in 2 patients in the SLPEC group and 9 patients in the TLPEC group, and there was a significant difference between the two groups (P = 0.04). However, the incidence of ipsilateral hernia recurrence, surgical site infection, suture-knot reactions and chronic inguinodynia did not significantly differ between the two groups (P = 0.332, 0.301, 0.332 and 0.599, respectively). Postoperative hydrocele occurred in only 1 male child in the SLPEC group and in no male children in the TLPEC group, and there was no difference between the two groups (P = 0.310). In this study, there were no cases of testicular atrophy or iatrogenic ascent of the testis. Compared with the TLPEC group, the SLPEC group had the advantages of a concealed incision, light scarring, minimal invasiveness, a reduced operation time, minimal bleeding, mild pain and rapid recovery. In conclusion, SLPEC using double-modified hernia needles with hydrodissection and high ligation of the hernia sac is a safe, effective and minimally invasive surgery. The cosmetic results are impressive, and the follow-up results are promising.
Postoperative pain is often undermanaged in surgical patients. In the outpatient surgery population, such as breast reduction surgery, postoperative pain can lead to increased narcotic use, increased nausea, surgical complications and unplanned hospital admission, in addition to patient discomfort or dissatisfaction. Tumescence is a method of infiltrating tissues, such as the breast, with solutions of very dilute lidocaine and/or very dilute epinephrine in order to provide diffuse local anesthesia, hemostasis, and tissue manipulation. Both types of solution are considered standard care and both at the University of Wisconsin, Madison. There are two main aims to this study. Aim 1 is to determine the effect of dilute lidocaine in tumescent solution on post-operative pain following breast reduction surgery. Aim 2 of our study is to determine the effect of dilute lidocaine in tumescent solution on secondary post-operative outcomes following breast reduction surgery. The secondary outcomes that will be measured in this study include average time (minutes) spent in the postanesthesia care unit (PACU), average time (minutes) spent in Phase 2, total time (minutes) between the end of case and discharge home, occurrence of unplanned hospital admission, number of episodes of post-operative nausea (subjective feeling vs. emesis) and amount of anti-emetic medication used in pacu, phase 2 and the first 24 hours post-op (mg). The investigators hypothesize that tumescence with lidocaine and epinephrine will have improved post-operative pain control leading to less narcotic use during the first twenty four hours postoperatively. (Aim 1). The investigators also believe that tumescence with lidocaine and epinephrine will lead to less time spent in PACU, less time spent in Phase2, less time between the end of the case and discharge home, less occurrence of unplanned hospital admissions, less episodes of post-operative nausea and less amount of antiemetic medication used in PACU, phase 2 and the first 24 hours post-op (Aim 2). The investigators propose that such differences could play a significant role in surgical outcomes and patient satisfaction in outpatient plastic surgery.
Film-coated tablet containing 15 mg of trifluridine and 7.065 mg of tipiracil hydrochloride, or 20 mg of trifluridine and 9.42 mg of tipiracil hydrochloride (with a molar ratio of 1:0.5) was administered at 35 mg/m²/dose orally twice a day, within 1 hour after completion of morning and evening meals, for 5 days on/2 days off, over 2 weeks, followed by a 14-day rest period. This treatment cycle was repeated every 4 weeks until treatment withdrawal criteria are met.
S. salivarius K12 group: The S. salivarius K12 lozenges (NOW Foods, USA) contained not less than 1×109 CFU viable cells of S. salivarius K12 as the active ingredient. The S. salivarius K12 lozenges were dissolved in the mouth and then swallowed through the first day of RT to the end of treatment (1 lozenge 3 times a day).
The study will be conducted in a group of 200 people aged 19-25. Posture assessment will concern the measurement of curvatures in the sagittal plane of the spine using a gravitational Rippstein plurimeter and performing a three-dimensional analysis of the spine using the DIERS 3D device. In addition, a modified Matthias test will be performed using the DIERS 3D device, where kyphosis and lordosis parameters in the sagittal plane of the spine at isometric tension of the spinal muscles will be assessed. The spinal motion in the sagittal and frontal planes will also be measured using a digital inclinometer. In the second stage of the study, the participants will participate in the activity in the form of endurance training "Nordic Walking" (NW) for a period of 8 weeks 3 times a week. The recording of energy expenditure during a normal day of activity will be done using an Actigraph GT3X accelerometer. After a period of 8 weeks, all measurements will be repeated.
The purpose of this study is to find out how differences in age can affect the duration of pain relief from a femoral nerve block. Complete recovery after leg surgery involves healing of tissues at the surgical site, recovery of muscle strength and range-of-motion. Some pain is normally experienced after leg surgery. At the hospital, pain is usually treated with pain medicines, and/or a nerve block procedure. A nerve block involves injecting a local anesthetic beside the nerves to numb the nerves that supply feeling to the knee joint and surrounding tissues. The choice as to whether a participant has a nerve block or not is made by the participant and their surgeon and is not determined by this research study. The study aim is to find out how long a nerve block can relieve postsurgical pain, and whether that duration is affected by the age of the participant.
An alternative HER-2/neu product, herstatin, consists of subdomains I and II from the ectodomain of p185HER-2 and a unique 79 amino acid C-terminus encoded by intron 8. Recombinant herstatin added to cells was found to bind and inhibit p185HER-2. The effects of ectopic expression of herstatin in combination with either p185HER-2 or with its homolog, the EGF receptor, was studied. Cotransfection of herstatin with HER-2 inhibited p185HER-2 levels and caused an approximate 8-fold reduction in p185 tyrosine phosphorylation. Inhibition of p185HER-2 tyrosine phosphorylation corresponded to a dramatic decline in colony formation by cells that coexpressed p185HER-2 and herstatin. Herstatin also interfered with EGF activation of the EGF receptor. For both p185HER-2 and the EGF receptor, the extent of inhibition was affected by the expression levels of herstatin relative to the receptor. Herstatin is an autoinhibitor of p185HER-2 and expands it's inhibitory activity to another member of the group I family of receptor tyrosine kinases, the EGF receptor.
Osteoarthritis (OA) of the knee (gonarthrosis) is a common medical condition and causes pain and disability. By 65 years of age, the majority of the US population has radiographic evidence of OA and 11% have symptomatic OA of the knee. In Japan, OA of the knee is more common due to the common sitting style with maximally flexed knees and parallel position of both legs.

High Tibial Osteotomy (HTO) for knee OA is a standard procedure in orthopedic surgery. Six years ago, HTO using TomoFix™ was introduced. Because Asian people have different geometric dimensions of the tibiae, an adaptation of size and shape was necessary, and the new TomoFix™ Small was developed. Although there is widespread literature concerning osteotomy for treating knee OA, literature assessing patient outcome after open wedge HTO using TomoFix™ is rare and for TomoFix™ Small, this data is still nonexistent. Therefore, the primary aim of the present multicenter study is to evaluate patient functional outcome using the KOOS. Since a proportion of patients with the indication for HTO refuse surgery and opt to receive conservative treatment, the functional results of patients treated with HTO using TomoFix™ Small will be compared with these patients.
GATA-binding protein 4 (GATA4) is recognized for its significant roles in embryogenesis and various cancers. Through bioinformatics and clinical data, it appears that GATA4 plays a role in breast cancer development. Yet, the specific roles and mechanisms of GATA4 in breast cancer progression remain elusive. In this study, we identify GATA4 as a tumor suppressor in the invasion and migration of breast cancer. Functionally, GATA4 significantly reduces the transcription of MMP9. On a mechanistic level, GATA4 diminishes MMP9 transcription by interacting with p65 at the NF-κB binding site on the MMP9 promoter. Additionally, GATA4 promotes the recruitment of HDAC1, amplifying the bond between p65 and HDAC1. This leads to decreased acetylation of p65, thus inhibiting p65's transcriptional activity on the MMP9 promoter. Moreover, GATA4 hampers the metastasis of breast cancer in vivo mouse model. In summary, our research unveils a novel mechanism wherein GATA4 curtails breast cancer cell metastasis by downregulating MMP9 expression, suggesting a potential therapeutic avenue for breast cancer metastasis.
The control group began to use soft rubber balls for isometric contraction exercise from the 2nd day to the 8th week after operation. 2 times a day in the morning and evening, 3 groups of training each time, each group holds the ball for 5 minutes, and rests for 90 seconds between groups. Each grip training must be completed 20 times within 1 minute (keep 3 seconds each time in the first week) , increase by 2 seconds every week, and keep each grasping time for 10 seconds from the 5th to the 8th week.
In this study, a computer-driven, phoneme-agnostic method was explored for assessing speech disorders (SDs) in children, bypassing traditional labor-intensive phonetic transcription. Using the SpeechMark® automatic syllabic cluster (SC) analysis, which detects sequences of acoustic features that characterize well-formed syllables, 1952 American English utterances of 60 preschoolers were analyzed [16 with speech disorder present (SD-P) and 44 with speech disorder not present (SD-NP)] from two dialectal areas. A four-factor regression analysis evaluated the robustness of seven automated measures produced by SpeechMark® and their interactions. SCs significantly predicted SD status (p < 0.001). A secondary analysis using a generalized linear model with a negative binomial distribution evaluated the number of SCs produced by the groups. Results highlighted that children with SD-P produced fewer well-formed clusters [incidence rate ratio (IRR) = 0.8116, p ≤ 0.0137]. The interaction between speech group and age indicated that the effect of age on syllable count was more pronounced in children with SD-P (IRR = 1.0451, p = 0.0251), suggesting that even small changes in age can have a significant effect on SCs. In conclusion, speech status significantly influences the degree to which preschool children produce acoustically well-formed SCs, suggesting the potential for SCs to be speech biomarkers for SD in preschoolers.