Miracle-dz/UniFAR-FTUs huggingface dataset:
Prognosis of Differentiated Thyroid Carcinoma with Initial Distant Metastasis: A Multicenter Study in Korea

Background Most patients with differentiated thyroid cancer (DTC) have a favorable prognosis. However, patients with DTC and initial distant metastasis have not been commonly found, and their clinical characteristics have seldom been reported. In this study, we analyzed the clinical features and prognosis of patients with DTC and initial distant metastasis in Korea. Methods We retrospectively reviewed the clinical data of 242 patients with DTC and initial distant metastasis treated from 1994 to 2013, collected from five tertiary hospitals in Korea. Results The patients' median age was 51 years, and 65% were women. They were followed for a median of 7 years. Lung was the most common site of distant metastasis: only lung 149 patients (62%), only bone 49 (20%), other single site one (pleura), and combined sites 43 (40 were lung and bone, two were bone and other site, and one was lung and other site). At the time of diagnosis, 50 patients (21%) had non-radioactive iodine (RAI) avidity. Five-year disease-specific survival (DSS) was 85% and 10-year DSS was 68%, which were better than those in previous studies. After multivariate analysis, old age, male sex, metastatic site, and histologic type (follicular type) were significant factors for poor prognosis. However, negative RAI avidity status was not a significant prognostic factor after adjusting for other variables. Conclusion The prognosis of Korean patients with DTC and initial distant metastasis was better than in previous studies. Old age, male sex, metastasis site, and histologic type were significant prognostic factors.
Liver HLA-E Expression Is Associated with Severity of Liver Disease in Chronic Hepatitis C

Hepatitis C virus (HCV) can escape from innate and adaptive immunity, making the immune response ineffective. Human leukocyte antigen E (HLA-E) might regulate the antiviral function of immune response and contribute to the persistence of HCV and the severity of liver disease. This study aimed to evaluate the expression of HLA-E in the liver and its association with the severity of liver disease in HCV patients. We performed a retrospective analysis of liver biopsies from 125 HCV patients and from 20 control subjects without liver disease. Liver biopsies were reviewed and classified according to severity of fibrosis and inflammatory activity. The pathologist assessed the magnitude of HLA-E expression in a semiquantitative way, attributing scores from 0 to 3. Immunohistochemistry showed positive for HLA-E in hepatocyte and Kupffer cells. The rate of HLA-E positivity in hepatocytes and Kupffer cells was significantly higher in HCV patients compared to controls. The liver samples classified as severe fibrosis and necroinflammatory activity presented greater expression of HLA-E on Kupffer cells and hepatocytes, with a significant linear association. It indicates that HLA-E expression may have an immunomodulatory effect and a possible role in the severity of liver disease in chronic hepatitis C.
An Input-Delay Event-Triggered Control Design for Nonlinear Systems

The paper proposes a novel event-triggered control scheme for nonlinear systems based on the input-delay method. Specifically, the closed-loop system is associated with a pair of auxiliary input and output. The auxiliary output is defined as the derivative of the continuous-time input function, while the auxiliary input is defined as the input disturbance caused by the sampling or equivalently the integral of the auxiliary output over the sampling period. As a result, a cyclic mapping forms from the input to the output via the system dynamics and back from the output to the input via the integral. The event-triggering law is constructed to make the mapping contractive such that the stabilization is achieved and an easy-to-check Zeno-free condition is provided. With this idea, we develop a theorem for the event-triggered control of interconnected nonlinear systems which is employed to solve the event-triggered control for lower-triangular systems with dynamic uncertainties.
A functional genetic screen reveals sequence preferences within a key tertiary interaction in cobalamin riboswitches required for ligand selectivity

Abstract Riboswitches are structured mRNA sequences that regulate gene expression by directly binding intracellular metabolites. Generating the appropriate regulatory response requires the RNA rapidly and stably acquire higher-order structure to form the binding pocket, bind the appropriate effector molecule and undergo a structural transition to inform the expression machinery. These requirements place riboswitches under strong kinetic constraints, likely restricting the sequence space accessible by recurrent structural modules such as the kink turn and the T-loop. Class-II cobalamin riboswitches contain two T-loop modules: one directing global folding of the RNA and another buttressing the ligand binding pocket. While the T-loop module directing folding is highly conserved, the T-loop associated with binding is substantially less so, with no clear consensus sequence. To further understand the functional role of the binding-associated module, a functional genetic screen of a library of riboswitches with the T-loop and its interacting nucleotides was used to build an experimental phylogeny comprised of sequences that possess a wide range of cobalamin-dependent regulatory activity. Our results reveal conservation patterns of the T-loop and its interaction with the binding core that allow for rapid tertiary structure formation and demonstrate its importance for generating strong ligand-dependent repression of mRNA expression.
Open source modules for tracking animal behavior and closed-loop stimulation based on Open Ephys and Bonsai

Objective. A major goal in systems neuroscience is to determine the causal relationship between neural activity and behavior. To this end, methods that combine monitoring neural activity, behavioral tracking, and targeted manipulation of neurons in closed-loop are powerful tools. However, commercial systems that allow these types of experiments are usually expensive and rely on non-standardized data formats and proprietary software which may hinder user-modifications for specific needs. In order to promote reproducibility and data-sharing in science, transparent software and standardized data formats are an advantage. Here, we present an open source, low-cost, adaptable, and easy to set-up system for combined behavioral tracking, electrophysiology, and closed-loop stimulation. Approach. Based on the Open Ephys system (www.open-ephys.org) we developed multiple modules to include real-time tracking and behavior-based closed-loop stimulation. We describe the equipment and provide a step-by-step guide to set up the system. Combining the open source software Bonsai (bonsai-rx.org) for analyzing camera images in real time with the newly developed modules in Open Ephys, we acquire position information, visualize tracking, and perform tracking-based closed-loop stimulation experiments. To analyze the acquired data we provide an open source file reading package in Python. Main results. The system robustly visualizes real-time tracking and reliably recovers tracking information recorded from a range of sampling frequencies (30–1000 Hz). We combined electrophysiology with the newly-developed tracking modules in Open Ephys to record place cell and grid cell activity in the hippocampus and in the medial entorhinal cortex, respectively. Moreover, we present a case in which we used the system for closed-loop optogenetic stimulation of entorhinal grid cells. Significance. Expanding the Open Ephys system to include animal tracking and behavior-based closed-loop stimulation extends the availability of high-quality, low-cost experimental setup within standardized data formats serving the neuroscience community.
Oral Health Status of Stroke Patients Related to Residual Symptoms: A Case-Control Epidemiological Study in Hungary.

PURPOSE Stroke is a leading cause of death in developed countries. Recently, its connection with oral health has been a focus of the medical literature. The aim of this study was therefore to statistically examine the oral health of subjects who previously suffered from stroke and provide a guide for the dental treatment of these patients. MATERIALS AND METHODS Stroke patients at least one year after the stroke episode and age- and sex-matched healthy controls were examined: dental and medical stroke histories were recorded, followed by a detailed orofacial examination. A categorisation into three 'dental' subgroups of stroke patients was carried out based on their residual symptoms, the functional deficiency of limbs, and chewing and swallowing difficulties. Indices quantifying oral hygiene (OHI-S), dental status explained by the number of decayed, missing, and filled teeth (DMFT), periodontal status (CAL, CPITN, Mühlemann index), and the status of prosthetic treatment (prosthetic index) were assessed. Statistical comparison was performed between the patient and age- and sex-matched control subjects, as well as between subgroups of stroke patients. RESULTS One hundred two stroke patients and 98 healthy age- and sex-matched control subjects were examined. The oral health and dental status of stroke patients was worse compared with the control group. Stroke patients had significantly more decayed (2.3 ± 3 vs1.1 ± 1.8; p = 0.01) and missing (19.3 ± 9.5 vs 15.5 ± 9.3; p = 0.005) teeth, but significantly fewer filled (3.6 ± 4.7 vs 7.7 ± 5.6; p < 0.001) teeth than did the healthy controls. In stroke patients, clinical attachment loss (CAL) was double that of the control group (p < 0.001). A comparison between the subgroups of stroke patients revealed that the most severe findings were in patients who had chewing and swallowing disabilities. DISCUSSION According to these results, the combination of risk factors of stroke, residual neurological signs after stroke, and poorer socioeconomic conditions results in poor oral hygiene, poor dental and periodontal conditions, and a lower prosthetic index. Special care and attention should be given to the oral hygiene and dental treatment of such patients, to enable good nourishment.
Occult Hepatitis C Virus Infection: A Review

Abstract Occult hepatitis C virus (HCV) infection (OCI), first described in 2004, is defined as the presence of HCV RNA in hepatocytes or peripheral blood mononuclear cells without detectable HCV RNA in the serum. Here, we aimed to review the epidemiology, diagnostic methods, clinical implications and potential management recommendations currently described in the literature, as well as the future directions for investigation of this entity. PubMed and Cochrane databases were searched with combination of the following keywords: “occult”, “hepatitis C virus”, and “occult HCV infection”. There are data to support OCI as a potential culprit in cryptogenic liver disease. There are also consistent data demonstrating the existence of OCI in specific populations, such as dialysis, human immunodeficiency virus-infected and hepatitis B virus-infected patients, and also in the general population. While the gold standard for diagnosis is liver biopsy, examination of peripheral blood mononuclear cells may be a reliable, safer alternative method of diagnosis. Occult HCV infection is likely associated with liver fibrosis and progression of liver disease. Additional studies are required to determine the infectivity of OCI patients, as well as clarify the natural course and specific clinical implications of OCI. Lastly, studies are needed to determine whether treatment of OCI leads to decreased morbidity and/or mortality.
Diagnostic performance of plasma and urine neutrophil gelatinase-associated lipocalin, cystatin C, and creatinine for acute kidney injury in burn patients: A prospective cohort study

Background Diagnosing acute kidney injury quickly is imperative since it is known as an independent risk factor for mortality in burn patients. We evaluated the diagnostic power of creatinine, cystatin, serum and urine neutrophil gelatinase-associated lipocalin at different time periods and observed the changes from baseline for each biomarker. Methods This was a prospective observation study from January 2015 to February 2016. A total of 84 patients were enrolled consecutively. Serum creatinine, serum cystatin C, and serum and urine neutrophil gelatinase-associated lipocalin were measured at admission, 7th, 14th, 21st, and 28th days after admission. All samples were collected until acute kidney injury developed. Results Acute kidney injury developed in 35 patients. The mean age was 49.6 years with a male predominance. The median urine neutrophil gelatinase-associated lipocalin was the lowest (11.6 ng/dL) at admission, and the highest at 85.5 ng/dL on day 7. Mean creatinine level was the highest (0.88 mg/dL) at admission and the median creatinine level was the lowest (0.56 mg/dL) on the 14th day. The area under the curve of creatinine levels was the highest with 0.857 during the 1st week. The area under the curve of urine neutrophil gelatinase-associated lipocalin was the highest with 0.803 during the 5th week. Conclusions Within 1 week of acute kidney injury, creatinine level was the optimal biomarker for diagnosis while urine neutrophil gelatinase-associated lipocalin showed better diagnostic performance following the 4- week period.
Dendritic Cells in the Cross Hair for the Generation of Tailored Vaccines

Vaccines represent the discovery of utmost importance for global health, due to both prophylactic action to prevent infections and therapeutic intervention in neoplastic diseases. Despite this, current vaccination strategies need to be refined to successfully generate robust protective antigen-specific memory immune responses. To address this issue, one possibility is to exploit the high efficiency of dendritic cells (DCs) as antigen-presenting cells for T cell priming. DCs functional plasticity allows shaping the outcome of immune responses to achieve the required type of immunity. Therefore, the choice of adjuvants to guide and sustain DCs maturation, the design of multifaceted vehicles, and the choice of surface molecules to specifically target DCs represent the key issues currently explored in both preclinical and clinical settings. Here, we review advances in DCs-based vaccination approaches, which exploit direct in vivo DCs targeting and activation options. We also discuss the recent findings for efficient antitumor DCs-based vaccinations and combination strategies to reduce the immune tolerance promoted by the tumor microenvironment.
Fertility Preservation for Patients with Malignant Disease. Guideline of the DGGG, DGU and DGRM (S2k-Level, AWMF Registry No. 015/082, November 2017) – Recommendations and Statements for Girls and Women

Aim The aim of this official guideline published by the German Society of Gynecology and Obstetrics (DGGG) and coordinated with the German Society of Urology (DGU) and the German Society of Reproductive Medicine (DGRM) is to provide consensus-based recommendations, obtained by evaluating the relevant literature, on counseling and fertility preservation for prepubertal girls and boys as well as patients of reproductive age. Statements and recommendations for girls and women are presented below. Statements or recommendations for boys and men are not the focus of this guideline. Methods This S2k guideline was developed at the suggestion of the guideline commission of the DGGG, DGU and DGRM and represents the structured consensus of representative members from various professional associations (n = 40). Recommendations The guideline provides recommendations on counseling and fertility preservation for women and girls which take account of the patientʼs personal circumstances, the planned oncologic therapy and the individual risk profile as well as the preferred approach for selected tumor entities.
Clinical significance of miRNA - 106a in non-small cell lung cancer patients who received cisplatin combined with gemcitabine chemotherapy

Objective: Research has demonstrated that microRNA (miR)-106a is related to cisplatin resistance. We investigated the expression of miR-106a in the serum of patients with non-small cell lung cancer (NSCLC) and their sensitivity to chemotherapy by cisplatin combined with gemcitabine. Methods: Eighty-five NSCLC patients, who completed four cycles of gemcitabine and cisplatin chemotherapy, volunteered for this study and their serum samples were collected. Serum samples from 60 healthy subjects were used as controls. Real-time quantitative polymerase chain reaction (real-time qPCR) was used to quantify the level of miR-106a in the serum. Demographic and survival data of these patients were collected for the analysis. Results: The expression of miR-106a in the serum of NSCLC patients was significantly higher than that of healthy subjects (P < 0.001). The expression of miR-106a was not correlated with patients' gender, age, tumor size, lymphatic metastasis, and pathological types; but was correlated with patients' tumor staging ( P = 0.003). After chemotherapy, serum miR-106a expression decreased in patients. The decrease in miR-106a expression in the chemotherapy-sensitive group was much higher than that in the chemotherapy-resistant group. Survival analysis shows that NSCLC patients with high expression of miR-106a have a poorer prognosis. The overall survival of NSCLC patients in the chemotherapy-sensitive group was significantly higher than that in the chemotherapy-resistant group. Conclusions: High expression of miR-106a may be involved in the development of NSCLC. MiR-106a has significance in the prognosis of NSCLC. The level of miR-106a in the serum can be a useful parameter in screening for drug resistance during cisplatin-based chemotherapy.
Developing Class III malocclusions: challenges and solutions

Class III malocclusion represents a growth-related dentofacial deformity with mandibular prognathism in relation to the maxilla and/or cranial base. Its prevalence varies greatly among and within different races, ethnic groups, and geographic regions studied. Class III malocclusion has a multifactorial etiology, which is the expression of a moderate distortion of normal development as a result of interaction between innate factors or genetic hereditary with environmental factors. Various skeletal topographies of underlying Class III malocclusion are due to discrepancy in the maxillary and mandibular growth along with vertical and/or transverse problems apart from sagittal malformations. The spectrum of complications for Class III malocclusion ranges in gravity from dentoalveolar problems with functional anterior shift of the mandible to true skeletal problems with serious maxillomandibular discrepancies, which makes its diagnosis highly challenging in growing children. Concern regarding early treatment and the need for interceptive care in the case of Class III malocclusion has always been a dilemma, knowing that not all problems will be solved in these cases until maxillomandibular growth is further completed, and the long-term outcome of various treatment approaches may depend on the growth tendency of an individual. Interceptive treatment of Class III malocclusions should be undertaken if it prevents damage to the oral tissues and/or significantly reduces the amount or severity of future orthodontic and surgical interventions. This paper presents an overview of developing Class III malocclusion, with the emphasis on challenges and their solutions based on the best current available evidence.
A multi‐scale model of the coronary circulation applied to investigate transmural myocardial flow

Distribution of blood flow in myocardium is a key determinant of the localization and severity of myocardial ischemia under impaired coronary perfusion conditions. Previous studies have extensively demonstrated the transmural difference of ischemic vulnerability. However, it remains incompletely understood how transmural myocardial flow is regulated under in vivo conditions. In the present study, a computational model of the coronary circulation was developed to quantitatively evaluate the sensitivity of transmural flow distribution to various cardiovascular and hemodynamic factors. The model was further incorporated with the flow autoregulatory mechanism to simulate the regulation of myocardial flow in the presence of coronary artery stenosis. Numerical tests demonstrated that heart rate (HR), intramyocardial tissue pressure (Pim), and coronary perfusion pressure (Pper) were the major determinant factors for transmural flow distribution (evaluated by the subendocardial‐to‐subepicardial (endo/epi) flow ratio) and that the flow autoregulatory mechanism played an important compensatory role in preserving subendocardial perfusion against reduced Pper. Further analysis for HR variation‐induced hemodynamic changes revealed that the rise in endo/epi flow ratio accompanying HR decrease was attributable not only to the prolongation of cardiac diastole relative to systole, but more predominantly to the fall in Pim. Moreover, it was found that Pim and Pper interfered with each other with respect to their influence on transmural flow distribution. These results demonstrate the interactive effects of various cardiovascular and hemodynamic factors on transmural myocardial flow, highlighting the importance of taking into account patient‐specific conditions in the explanation of clinical observations.
Biochemical control systems for small molecule damage in plants

ABSTRACT As a system, plant metabolism is far from perfect: small molecules (metabolites, cofactors, coenzymes, and inorganic molecules) are frequently damaged by unwanted enzymatic or spontaneous reactions. Here, we discuss the emerging principles in small molecule damage biology. We propose that plants evolved at least three distinct systems to control small molecule damage: (i) repair, which returns a damaged molecule to its original state; (ii) scavenging, which converts reactive molecules to harmless products; and (iii) steering, in which the possible formation of a damaged molecule is suppressed. We illustrate the concept of small molecule damage control in plants by describing specific examples for each of these three categories. We highlight interesting insights that we expect future research will provide on those systems, and we discuss promising strategies to discover new small molecule damage-control systems in plants.