anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
BACKGROUND: To provide a preoperative prediction model for lymph node metastasis in pancreatic cancer patients and provide molecular information of key radiomic features.
METHODS: Two cohorts comprising 151 and 54 pancreatic cancer patients were included in the analysis. Radiomic features from the tumor region of interests were extracted by using PyRadiomics software. We used a framework that incorporated 10 machine learning algorithms and generated 77 combinations to construct radiomics-based models for lymph node metastasis prediction. Weighted gene coexpression network analysis (WGCNA) was subsequently performed to determine the relationships between gene expression levels and radiomic features. Molecular pathways enrichment analysis was performed to uncover the underlying molecular features.
RESULTS: Patients in the in-house cohort (mean age, 61.3 years ± 9.6 [SD]; 91 men [60%]) were separated into training (n = 105, 70%) and validation (n = 46, 30%) cohorts. A total of 1,239 features were extracted and subjected to machine learning algorithms. The 77 radiomic models showed moderate performance for predicting lymph node metastasis, and the combination of the StepGBM and Enet algorithms had the best performance in the training (AUC = 0.84, 95% CI = 0.77-0.91) and validation (AUC = 0.85, 95% CI = 0.73-0.98) cohorts. We determined that 15 features were core variables for lymph node metastasis. Proliferation-related processes may respond to the main molecular alterations underlying these features.
CONCLUSIONS: Machine learning-based radiomics could predict the status of lymph node metastasis in pancreatic cancer, which is associated with proliferation-related alterations.
FIELD: medicine. ^ SUBSTANCE: method of purification of human factor VIIa includes creation of affine sorbent, which includes immobilisation of antibodies to factor VIIa on insoluble matrix, sorption of factor VIIa on affine sorbent, further evolution of factor VII a and control of correctedness of its post-translation modification and conformation. Obtaining affine sorbent is achieved by optimal combination of NHS-activated Sepharose 4FF as hard base and combination of monoclonal antibodies, produced by clones 4F4 and 6B8 of cultivated hybridioma, selected by the highest degree of output of monoclonal antibodies to epitopes of calcium-binding domain in composition of factor VIIa. Control of correctness of post-translation modification and conformation of factor VIIa is performed by immunoassay with application of boards covered with monoclonal antibodies, produced by clone 5D9. 95%-binding of affine sorbent with factor VII a is achieved after 5 minutes of contact with one cycle of interaction with sorbent. ^ EFFECT: reduction of factor VII purification time and expenditures on said process. ^ 4 ex, 4 dwg, 7 tbl
Heterozygous missense variants and in-frame indels in SMC3 are a cause of Cornelia de Lange syndrome (CdLS), marked by intellectual disability, growth deficiency, and dysmorphism, via an apparent dominant-negative mechanism. However, the spectrum of manifestations associated with SMC3 loss-of-function variants has not been reported, leading to hypotheses of alternative phenotypes or even developmental lethality. We used matchmaking servers, patient registries, and other resources to identify individuals with heterozygous, predicted loss-of-function (pLoF) variants in SMC3, and analyzed population databases to characterize mutational intolerance in this gene. Here, we show that SMC3 behaves as an archetypal haploinsufficient gene: it is highly constrained against pLoF variants, strongly depleted for missense variants, and pLoF variants are associated with a range of developmental phenotypes. Among 14 individuals with SMC3 pLoF variants, phenotypes were variable but coalesced on low growth parameters, developmental delay/intellectual disability, and dysmorphism, reminiscent of atypical CdLS. Comparisons to individuals with SMC3 missense/in-frame indel variants demonstrated an overall milder presentation in pLoF carriers. Furthermore, several individuals harboring pLoF variants in SMC3 were nonpenetrant for growth, developmental, and/or dysmorphic features, and some had alternative symptomatologies with rational biological links to SMC3. Analyses of tumor and model system transcriptomic data and epigenetic data in a subset of cases suggest that SMC3 pLoF variants reduce SMC3 expression but do not strongly support clustering with functional genomic signatures of typical CdLS. Our finding of substantial population-scale LoF intolerance in concert with variable growth and developmental features in subjects with SMC3 pLoF variants expands the scope of cohesinopathies, informs on their allelic architecture, and suggests the existence of additional clearly LoF-constrained genes whose disease links will be confirmed only by multilayered genomic data paired with careful phenotyping.
Leucovorin is a racemic mixture of the diastereoisomers of the 5-formyl derivative of tetrahydrofolic acid. The biologically active compound of the mixture is the (-)- L-isomer, known as Citrovorum factor, or (-)-folinic acid. Leucovorin does not require reduction by the enzyme dihydrofolate reductase in order to participate in reactions utilizing folates as a source of “one-carbon” moieties. Following oral administration, leucovorin is rapidly absorbed and enters the general body pool of reduced folates. The increase in plasma and serum folate activity (determined microbiologically with Lactobacillus casei) seen after oral administration of leucovorin is predominantly due to 5-methyltetrahydrofolate. 

Twenty normal men were given a single, oral 15 mg dose (7.5 mg/m 2) of leucovorin calcium and serum folate concentrations were assayed with L. casei. Mean values observed (± one standard error) were: 

  1. Time to peak serum folate concentration: 1.72 ± 0.08 hours,
  2. Peak serum folate concentration achieved: 268 ± 18 ng/mL,
  3. Serum folate half-disappearance time: 3.5 hours.



Oral tablets yielded areas under the serum folate concentration-time curves (AUCs) that were 12% greater than equal amounts of leucovorin given intramuscularly and equal to the same amounts given intravenously.

Oral absorption of leucovorin is saturable at doses above 25 mg. The apparent bioavailability of leucovorin was 97% for 25 mg, 75% for 50 mg and 37% for 100 mg.
BACKGROUND: COVID-19 is an infectious pathology that shows vascular changes during pregnancy, as well as in the placentas. The main objectives of this study were to estimate the prevalence and the risk factors for preeclampsia in hospitalized pregnant women with COVID-19. As well as comparing maternal and perinatal outcomes in hospitalized pregnant women with COVID-19 and preeclampsia with those without preeclampsia.
METHODS: Prospective cohort study of 100 hospitalized pregnant women from two tertiary hospitals, diagnosed with COVID-19, and divided into two groups: PE+ group (pregnant women with COVID-19 and preeclampsia) and PE- group (pregnant women with COVID-19 without preeclampsia). These pregnant women had prevalence, risk factors, maternal and perinatal data analyzed.
RESULTS: The prevalence of preeclampsia was 11%. Severe COVID-19 was the main risk factor for preeclampsia (OR = 8.18 [CI 1.53-43.52]), as well as fetal growth restriction was the main perinatal outcome (OR = 8.90 [CI 1.52-38.4]). Comorbidities were more frequent in the PE+ group (63.6% vs 31.5%, p = 0.03), as well as prematurity (81.8% vs 41.6%, p = 0.02), low birth weight (63.6% vs 24.7%, p = 0.01), and the need for neonatal intensive care admission of the newborn (63.6% vs 27.0%, p = 0.03). Pregnant women with PE had twice as long a length of stay in the intensive care unit (RR = 2.35 [CI 1.34-4.14]). Although maternal mortality was more frequent among pregnant women with PE, it was not statistically significant.
CONCLUSIONS: Prevalence of preeclampsia in hospitalized pregnant women with COVID-19 was 11%. Severe COVID-19 was the main risk factor for preeclampsia and associated comorbidities increased the risk for developing preeclampsia. Long length of stay in the intensive care unit was the main maternal outcome and fetal growth restriction was the main perinatal outcome of preeclampsia.
A query processing server for providing scalable architectures in repricing is provided. The query processing server includes a gateway platform for processing communications and a repricing engine. The query processing server processor is configured to receive a repricing request from a frontend server. The query processing server processor is also configured to define a set of repricing periods. The query processing server processor is further configured to transmit a creation instruction to the repricing database server to create a repricing status database and queue. The query processing server processor is also configured to determine a set of claims data queries for execution based on the set of scenario data and to query the repricing database server with the set of claims data queries. The query processing server processor is configured to perform a repricing analysis using the set of claims data responses and the set of repricing periods.
INTRODUCTION: Little has been reported about the clinical relevance and trajectories of symptoms in end-stage liver disease (ESLD). The purpose of this prospective study was to identify trajectories of change in symptom burden over the course of 12 months in adults with ESLD.
METHODS: Patients were recruited from hepatology clinics at 2 healthcare systems. Validated measures were used to assess physical and psychological symptoms. Latent growth mixture modeling and survival and growth modeling were used to analyze the survey data.
RESULTS: Data were available for 192 patients (mean age 56.5 ± 11.1 years, 64.1% male, mean Model for ESLD (MELD) 3.0 19.2 ± 5.1, ethyl alcohol as primary etiology 33.9%, ascites 88.5%, encephalopathy 70.8%); there were 38 deaths and 39 liver transplantations over 12 months. Two symptom trajectories were identified: 62 patients (32.3%) had high and unmitigated symptoms, and 130 (67.7%) had lower and improving symptoms. Patients with high and unmitigated symptoms had twice the hazard of all-cause mortality (subhazard ratio 2.53, 95% confidence interval: 1.32-4.83) and had worse physical ( P < 0.001) and mental quality of life ( P = 0.012) compared with patients with lower and improving symptoms. Symptom trajectories were not associated with MELD 3.0 scores ( P = 0.395). Female sex, social support, and level of religiosity were significant predictors of symptom trajectories ( P < 0.05 for all).
DISCUSSION: There seems to be 2 distinct phenotypes of symptom experience in patients with ESLD that is independent of disease severity and associated with sex, social support, religiosity, and mortality. Identifying patients with high symptom burden can help optimize their care.
OBJECTIVE: Anorexia nervosa is associated with low bone mineral density (BMD) and deficits in bone microarchitecture and strength. Low BMD is common in atypical anorexia nervosa, in which criteria for anorexia nervosa are met except for low weight. We investigated whether women with atypical anorexia nervosa have deficits in bone microarchitecture and estimated strength at the peripheral skeleton.
METHOD: Measures of BMD and microarchitecture were obtained in 28 women with atypical anorexia nervosa and 27 controls, aged 21-46 years.
RESULTS: Mean tibial volumetric BMD, cortical thickness, and failure load were lower, and radial trabecular number and separation impaired, in atypical anorexia nervosa versus controls (p < .05). Adjusting for weight, deficits in tibial cortical bone variables persisted (p < .05). Women with atypical anorexia nervosa and amenorrhea had lower volumetric BMD and deficits in microarchitecture and failure load versus those with eumenorrhea and controls. Those with a history of overweight/obesity or fracture had deficits in bone microarchitecture versus controls. Tibial deficits were particularly marked. Less lean mass and longer disease duration were associated with deficits in high-resolution peripheral quantitative computed tomography (HR-pQCT) variables in atypical anorexia nervosa.
DISCUSSION: Women with atypical anorexia nervosa have lower volumetric BMD and deficits in bone microarchitecture and strength at the peripheral skeleton versus controls, independent of weight, and particularly at the tibia. Women with atypical anorexia nervosa and amenorrhea, less lean mass, longer disease duration, history of overweight/obesity, or fracture history may be at higher risk. This is salient as deficits in HR-pQCT variables are associated with increased fracture risk.
PUBLIC SIGNIFICANCE: Atypical anorexia nervosa is a psychiatric disorder in which psychological criteria for anorexia nervosa are met despite weight being in the normal range. We demonstrate that despite weight in the normal range, women with atypical anorexia nervosa have impaired bone density, structure, and strength compared to healthy controls. Whether this translates to an increased risk of incident fracture in this population requires further investigation.
NLP; Neurolinguistic programming 8 weeks of practice once a week for 20 minutes each. Neurolinguistic programming will be carried out online. Mothers will actively participate.
Groups of subjects will receive a weekly infusions of KHK2866 as treatment for advanced cancer. If there no severe side effects, the dose will be increased for future subjects. A total of four groups are anticipated. Once an acceptable dose is determined an additional seven subjects will be treated at that dose.
Account for patients with wild type EGFR, sample attrition , incidence rate of symptomatic brain metastasis(10%) and any other reasons for screen failure rate(50%), it is esimated that 88 patients will be randomized from 5 sites. Patients will be randomized 1:1, the experimental arm is upfront Osimertinib with WBI sequential therapy, while the control arm is Osimertinib plus WBI. Osimertinib at a dose of 80 mg once per day, until unacceptable adverse events or disease progression occurred. WBI could be given to patients in experimental arm at any time base on investigator's decision after treatment initiated. Patients will be stratifed at randomization by GPA score (3.5-4 vs \<3.5) and the mutation type (Ex19Del / L858R). Patients will undergo the neurocognition, efficacy and safety assessments at baseline, and every 8 weeks until treatment is completed or discontinued. About time to brain metastases symptoms deterioration, the assessment was repeated in the first week (on site), second week (through telephone) and fourth week (on site). The rest assessment will be as well as other evaluations repeated every 8 weeks. To evaluate the correlation and predictive or prognostic value between gene dynamic changes and clinical efficacy, the tissue, plasma and cerebrospinal fluid (CSF) samples will be collected at baseline. CSF will be collected in patients with intracranial progression. Plasma will be collected in all the patients at disease progression, while tissue is optional. Also, plasma will be collected at week 8(first evaluation of efficacy).
Cross-sectional studies have demonstrated strong associations between physical frailty and depression. However, the evidence from prospective studies is limited. Here, we analyze data of 352,277 participants from UK Biobank with 12.25-year follow-up. Compared with non-frail individuals, pre-frail and frail individuals have increased risk for incident depression independent of many putative confounds. Altogether, pre-frail and frail individuals account for 20.58% and 13.16% of depression cases by population attributable fraction analyses. Higher risks are observed in males and individuals younger than 65 years than their counterparts. Mendelian randomization analyses support a potential causal effect of frailty on depression. Associations are also observed between inflammatory markers, brain volumes, and incident depression. Moreover, these regional brain volumes and three inflammatory markers-C-reactive protein, neutrophils, and leukocytes-significantly mediate associations between frailty and depression. Given the scarcity of curative treatment for depression and the high disease burden, identifying potential modifiable risk factors of depression, such as frailty, is needed.
BACKGROUND: Next-generation sequencing (NGS) technologies offer fast and inexpensive identification of DNA sequences. Somatic sequencing is among the primary applications of NGS, where acquired (non-inherited) variants are based on comparing diseased and healthy tissues from the same individual. Somatic mutations in genetic diseases such as cancer are tightly associated with genomic instability. Genomic instability increases heterogenity, complicating sequencing efforts further, a task already challenged by the presence of short reads and repetitions in human DNA. This leads to low concordance among studies and limits reproducibility. This limitation is a significant problem since identified mutations in somatic sequencing are major biomarkers for diagnosis and the primary input of targeted therapies. Benchmarking studies were conducted to assess the error rates and increase reproducibility. Unfortunately, the number of somatic benchmarking sets is very limited due to difficulties in validating true somatic variants. Moreover, most NGS benchmarking studies are based on relatively simpler germline (inherited) sequencing. Recently, a comprehensive somatic sequencing benchmarking set was published by Sequencing Quality Control Phase 2 (SEQC2). We chose this dataset for our experiments because it is a well-validated, cancer-focused dataset that includes many tumor/normal biological replicates. Our study has two primary goals. First goal is to determine how replicate-based consensus approaches can improve the accuracy of somatic variant detection systems. Second goal is to develop highly predictive machine learning (ML) models by employing replicate-based consensus variants as labels during the training phase.
RESULTS: Ensemble approaches that combine alternative algorithms are relatively common; here, as an alternative, we study the performance enhancement potential of biological replicates. We first developed replicate-based consensus approaches that utilize the biological replicates available in this study to improve variant calling performance. Subsequently, we trained ML models using these biological replicates and achieved performance comparable to optimal ML models, those trained using high-confidence variants identified in advance.
CONCLUSIONS: Our replicate-based consensus approach can be used to improve variant calling performance and develop efficient ML models. Given the relative ease of obtaining biological replicates, this strategy allows for the development of efficient ML models tailored to specific datasets or scenarios.
<P>PROBLEM TO BE SOLVED: To provide an affected part coating material for external application, capable of efficiently making a target harmful matter inactive by the photocatalytic reaction without giving the tissue and cells of an affected part serious damage caused by the photocatalytic reaction.  <P>SOLUTION: The affected part coating material 20 consists of a protection layer 25, a sterilization layer 24, and a water absorbing layer 22 which are layered one after another. The base material of the sterilization layer 24 is a porous sheet, and typically, a powder photocatalyst 26 is carried in the sterilization layer. The protection layer 25 consists of a porous sheet with gaps of such a size as can receive an exudate etc. from the affected part S. The base material of the absorbing layer 22 is a porous sheet, and an exudate absorbent material such as alginate is included in the absorbent layer.  <P>COPYRIGHT: (C)2004,JPO&NCIPI
Malignant forms of meningioma, such as atypical and anaplastic meningiomas, commonly relapse. Recently, there have been many reports elucidating the molecular biological mechanisms underlying meningioma recurrence. Tumors with loss of CDKN(cyclin dependent kinase)2A and 2B or lack of the tri-methylation of lysine 27 on histone H3 protein have a particularly high recurrence rate. In general, primary treatment for recurrent meningiomas comprises stereotactic radiosurgery(SRS)or stereotactic radiotherapy(SRT). However, re-operation is recommended for SRS-, SRT-refractory tumors. One of the benefits of reoperation is that it allows tumor control while decompressing the normal tissue, and changing the tumor microenvironment. Another is that it facilitates the acquisition of pathological and molecular genetic information, which can enable clinicians to recommend precision medicine. However, during reoperation, it is often difficult to detach the tumor from the surrounding brain tissue and cranial nerves because of severe adhesion. In cases of malignant meningiomas with multiple relapses, it is important to share the purpose and goal of the surgery with the patients and their families. In other words, which is being prioritized more, a high resection rate or functional outcomes? Furthermore, salvage surgery should also be a consideration.
PURPOSE:Cosmetic containing microcapsules of inorganic substance wall, having a colorant in them. CONSTITUTION:Cosmetic blended with microcapsules of inorganic substance wall having 0.1-30mum as a colorant component, comprising at least one of alkaline earth metal carbonate, alkaline earth metal silicate, alkaline earth metal phosphate, alkaline earth metal sulfate, metal oxide, metal hydroxide, metal silicate, and metal carbonate as a wall substance, and at least one of colorants, or a mixture of at least one colorants and at least one of extender pigment as a nucleated substance. EFFECT:A colorant component has uniform physical and chemical properties. Products will cause neither color separation nor color unevenness, etc. The colorant component will not cause aggregation, solidification, precipitation, etc. Titanium dioxide coated mica, etc. to be easily destroyed are easily protected. Defects of tar dye are solved and its improved color characteristics can be effectively utilized.
Affective disorder during pregnancy is a common and severe condition, associated with a higher risk for prenatal complications, preterm delivery, a higher rate of surgical birth and vaginal operative delivery. Depressed pregnant women are at risk for inadequate nutrition, poor weight gain, increased use of nicotine, drugs and alcohol, and failure to obtain adequate prenatal care, as well as poor mother-child attachment. Their infants have a higher risk for low birth weight, a higher rate of admission to neonatal intensive care, and cognitive, emotional and behavioural disturbances.Treatment of antepartum depression requires careful judgement to minimise risk to the foetus. Pharmacological treatment is an option, but all antidepressants cross the placenta, and both practitioners and patients are concerned about possible teratogenicity, pre- and perinatal adverse effects for the infant, as well as negative effects on long-term development. Thus, psychiatric medication use for depression in pregnancy may also pose an excess risk of preterm delivery and withdrawal symptoms in the newborn. Treatment of depression during pregnancy that is efficacious, reliable, safe, and with minor side effects is an urgent unmet clinical need. Light therapy may provide this somatic, non-pharmaceutical alternative. It is well established as the treatment of choice for Seasonal Affective Disorder (SAD), and there is a growing data base for response in nonseasonal major depression. Two promising pilot studies led to the present randomised, double-blind, placebo-controlled trial of 5 weeks daily morning bright light therapy (1h, 7000 lux white) compared with low-intensity placebo light therapy (1h, 70 lux red).