Miracle-dz/UniFAR-FTUs huggingface dataset:
Treatment Algorithm for Intermediate and Advanced Stage Hepatocellular Carcinoma: Korea

The practice guideline for hepatocellular carcinoma (HCC) in Korea was revised in 2009. It was based on clinical evidence. The treatment algorithm was divided into curative and noncurative treatments. According to Barcelona Clinic Liver Cancer (BCLC) staging, the curative treatment group included early stage HCC (BCLC-A), and the noncurative treatment group consisted of intermediate and advanced stages of HCC (BCLC-B, C). The intermediate stage of HCC stands for noncurative disease, and therefore surgical resection and radiofrequency ablation are not considered as primary treatment modalities. Transarterial chemoembolization (TACE) forms the backbone of the treatment for intermediate stage HCC with Child-Pugh A cirrhosis. Patients in whom complete necrosis is not achieved or early recurrence after TACE develops should receive individualized treatments such as systemic treatment or combined radiation therapy (RT). Liver transplantation (LT) can be carried out for intermediate stage HCCs. However, the long-term survival rate after LT for intermediate stage HCCs is inferior to that of early stage HCCs because intermediate stage HCCs exceed the Milan criteria. In patients with Child-Pugh C liver function, LT would be better than TACE in terms of survival gain if the tumor burden is acceptable by expert opinion standards. The treatment algorithm becomes very complicated when it comes to advanced stage HCC. Sorafenib, a multikinase inhibitor with antiangiogenic and antiproliferative properties, has been shown to prolong the median overall survival and the median time to radiological progression compared to placebo in randomized controlled trials (RCTs) and has become the current standard of care for patients with advanced-stage tumors not suitable for surgical or locoregional therapies. RT is in the process of becoming a modality with a high efficacy and minimum side effects for HCC treatment, with recent improvements in equipment as well as radiation methods. However, to discover whether RT is really beneficial in the treatment of large-sized intermediate and advanced stage HCC, prospective RCTs should be carried out.
Emerging drugs for panic disorder

Introduction: Panic disorder (PD) is a common anxiety disorder impairing strongly quality of life with high social costs. Effective anti-panic medications exist but a substantial proportion of patients do not fully respond, the available drugs have several side effects and most medications have a delayed onset of their therapeutic effect. Thus, further advances are needed. Areas covered: We review available data on emerging drugs for the treatment of PD including those in development, such as metabotropic glutamate II receptor agonists, D-cycloserine and levetiracetam, and new compounds with potential efficacy that may be relevant for future developments, such as modulators of cholinergic and orexin systems. Expert opinion: To date, the pharmacological research on PD appears to be relatively limited and probably still needs more time before making available new advances beyond the currently used medications. Many reasons may explain these difficulties, including the heterogeneity of the disorder, the incomplete understanding of its underlying pathophysiological mechanisms and difficulties in the selection of appropriate animal models in preclinical studies. Defining biomarkers and endophenotypes in PD may offer advantages in both understanding the pathophysiology of the disorder and selecting appropriate targets and outcomes for planning future pharmacological research.
Immunomodulatory activities and subacute toxicity of a novel β-glucan from Paenibacillus polymyxa JB115 in rats

Subacute toxicity and immunopharmacological activities of β-glucan from P. polymyxa JB115 was evaluated in a 28-day feeding study in rats. The white blood cell count, red blood cell count, hematocrit, hemoglobin, thrombocytes (THR) and thrombocytocrit were significantly higher in male fed with β-glucan than control rats and the insignificant lower eosinophil count, mean corpuscular volume, mean cell hemoglobin and uninfected THR (uTHR) levels were observed in male whereas no marked changes in female rats. No other significant differences in serum chemistry and liver, kidney, and spleen weights were observed. The pathological changes and other abnormal indicators were not detected in urine. Female rats fed with diet supplemented with 0.01% β-glucan also showed marked increase in the percentage of blood cytotoxic T-lymphocytes compared to that of the control group while not significant differences in the percentage of blood B-lymphocytes. No adverse effects on general condition and behavior, growth, feed and water consumption and feed conversion efficiency were found. The results suggest that consumption of the novel β-1, 3/1, 6-glucan from P. polymyxa JB115 was not associated with any obvious toxic effects in rats, indicating its safety as a potential immunostimulant or as an adjuvant of some animal vaccines.
Gene Therapy in Musculoskeletal Repair

Abstract: Local and regional gene therapy has improved healing in preclinical trials of articular and other muculoskeletal conditions. Combinations of cell supplementation and cells overexpressing growth factor genes have shown promising results for improving cartilage repair, enhancing delayed union of fractures, and driving organized tendon repair. Proof of concept has been developed using viral vectors, predominantly adenovirus, to deliver growth factor genes, such as BMP‐2, TGF‐β1, and IGF‐I. Integrating vectors, such as retrovirus and lentivirus, have improved the duration of gene‐induced repair, however, increased risk factors have limited broad application. Cartilage repair can be improved using chondrocyte or stem cell transplantation with cells expressing IGF‐I, BMP‐2, or FGF‐2. In cartilage injury and secondary osteoarthritis models, a combination of IL‐1 knockdown and growth factor supplementation has restored cartilage matrix and stabilized the osteoarthritic process. Ultimately, nonviral vectors may provide similar control of catabolic activity in cartilage and synovial structures, which may further improve outcome after chondrocyte or mesenchymal stem cell (MSC) implantation. MSCs derived from bone marrow, fat, or other connective tissues provide a multipotent cell source that may be privileged vectors for skeletal gene therapy. MSCs expressing BMP‐2, TGF‐β1, LMP‐1, IGF‐I, or GDF‐5 have enhanced cartilage, bone, and tendon repair. Overall, the field of orthopedic gene therapy for enhanced tissue repair has made significant preclinical advances. Combining existing cell transplant technology to deliver differentiated cells in a minimally invasive way, with genes that improve matrix formation, provides a manageable protocol for a persisting anabolic impact.
Young adults' recreational social environment as a predictor of ecstasy use initiation: findings of a population-based prospective study.

AIMS To examine prospectively the contribution of the recreational social environment to ecstasy initiation. DESIGN Population-based retrospective/prospective cohort study. SETTING Data from screening an Australian young adult population to obtain samples of users and non-users of ecstasy. PARTICIPANTS A sample of 204 ecstasy-naive participants aged 19-23 years was obtained, and a 6-month follow-up identified those who initiated ecstasy use. MEASUREMENTS We assessed a range of predictors of ecstasy initiation, including elements of participants' social environment, such as ecstasy-using social contacts and involvement in recreational settings. FINDINGS More than 40% of ecstasy-naive young adults reported ever receiving ecstasy offers. Ecstasy initiation after 6 months was predicted independently by having, at recruitment, many ecstasy-using social contacts [adjusted relative risk (ARR) 3.15, 95% confidence interval (CI): 1.57, 6.34], attending electronic/dance music events (ARR 6.97, 95% CI: 1.99, 24.37), receiving an ecstasy offer (ARR 4.02, 95% CI: 1.23, 13.10), early cannabis use (ARR 4.04, 95% CI: 1.78, 9.17) and psychological distress (ARR 5.34, 95% CI: 2.31, 12.33). Adjusted population-attributable fractions were highest for ecstasy-using social contacts (17.7%) and event attendance (15.1%). CONCLUSIONS In Australia, ecstasy initiation in early adulthood is associated predominantly with social environmental factors, including ecstasy-using social contacts and attendance at dance music events, and is associated less commonly with psychological distress and early cannabis use, respectively. A combination of universal and targeted education programmes may be appropriate for reducing rates of ecstasy initiation and associated harms.
A Comparative Experimental Study of Robust Sliding Mode Control Strategies for Underactuated Systems

This paper presents a comprehensive comparative study for the tracking control of a class of underactuated nonlinear uncertain systems. A given nonlinear model of the underactuated system is, at first stage, transformed into an input output form and the driving applied control input of the transformed system is then designed via four sliding mode control strategies, i.e., conventional first-order sliding mode control (SMC), second-order SMC, fast terminal SMC, and integral SMC. At the second stage, a ball and beam system is considered and the aforementioned four control design strategies are experimentally implemented. A comprehensive comparative study of the simulation and experimental results is then conducted, which take into account the tracking performance, i.e., settling time, overshoots, robustness enhancement, chattering reduction, sliding mode convergences, and control efforts.
Infectious Nickel Tolerance: A Reciprocal Interplay of Tolerogenic APCs and T Suppressor Cells That Is Driven by Immunization 1

Previously, we reported that tolerance to nickel, induced by oral administration of Ni2+ ions, can be adoptively transferred to naive mice with only 102 splenic T cells. Here we show that 102 T cell-depleted spleen cells (i.e., APCs) from orally tolerized donors can also transfer nickel tolerance. This cannot be explained by simple passive transfer of the tolerogen. The APCs from orally tolerized donors displayed a reduced allostimulatory capacity, a tolerogenic phenotype, and an increased expression of CD38 on B cells. In fact, it was B cells among the APCs that carried the thrust of tolerogenicity. Through serial adoptive transfers with Ly5.1+ donors and two successive sets of Ly5.2+ recipients, we demonstrated that nickel tolerance was infectiously spread from donor to host cells. After the transfer of either T cells or APCs from orally tolerized donors, the spread of tolerance to the opposite cell type of the recipients (i.e., APCs and T cells, respectively) required recipient immunization with NiCl2/H2O2. For the spread of tolerance from a given donor cell type, T cell or APC, to the homologous host cell type, the respective opposite cell type in the host was required as intermediate. We conclude that T suppressor cells and tolerogenic APCs induced by oral administration of nickel are part of a positive feedback loop that can enhance and maintain tolerance when activated by Ag associated with a danger signal. Under these conditions, APCs and T suppressor effector cells infectiously spread the tolerance to naive T cells and APCs, respectively.
Serum levels of sex hormone binding globulin (SHBG) are not predictive of prostate cancer diagnosis and aggressiveness: results from an Italian biopsy cohort.

PURPOSE To explore the association between serum levels of Sex Hormone Binding Globulin (SHBG) and the risk of developing prostate cancer (PCa) as well as high grade disease in men undergoing prostate biopsy. MATERIALS AND METHODS Between 2006 and 2012, we prospectively enrolled 740 patients with no history of PCa undergoing prostate biopsy. Before biopsy general data of the patient DRE, PSA and BMI were recorded. The risk of detecting cancer and high grade cancer was assessed as a function of SHBG using crude and adjusted logistic regressions. RESULTS Serum levels of SHBG were not associated with an increased risk of PCa or high grade disease. Age (OR 1.027 95% CI 1.003-1.052 p = 0.027), DRE (OR 3.391 95% CI 2.258-5.092 p = 0.000) and PSA (OR 1.078 95% CI 1.037-1.120 p = 0.000) were found to be independent predictors of prostate cancer risk. Age (OR 1.051 95% CI 1.009-1.095 p = 0.016), DRE (OR 2.519 95% CI 1.384-4.584 p = 0.000), BMI (OR 1.098 95% CI 1.011-1.193 p = 0.027) and PSA (OR 1.074 95% CI 1.014-1.137 p = 0.015) were found to be independent predictors of high grade disease. CONCLUSIONS In our cohort of patients, serum levels of SHBG are not predictive of PCa or high grade disease. According to our experience SHBG should not be considered a biomarker in PCa diagnosis neither a marker for high grade disease.
Mandibular distraction to relieve airway obstruction in children with cerebral palsy.

OBJECTIVE To determine the effectiveness of distraction osteogenesis of the mandible for relief of airway obstruction in neurologically impaired children. DESIGN Prospective pilot study. SETTING Tertiary care children's hospital. PATIENTS Five children with upper airway obstruction secondary to hypotonia were identified by airway endoscopy, pulse oximetry, and polysomnography. Four children were tracheotomy-dependent because of upper airway obstruction, and 1 was being considered for tracheotomy because of progressive airway obstruction. INTERVENTIONS All patients underwent distraction osteogenesis of the mandible for relief of their airway obstruction. MAIN OUTCOME MEASURES Treatment success was determined by endoscopy, continuous pulse oximetry, and polysomnography. RESULTS Four of the 5 children underwent distraction osteogenesis of the mandible with successful resolution of airway obstruction or tracheotomy decannulation. One child did not show adequate improvement of upper airway obstruction and remained tracheotomy-dependent. Follow-up was 2 to 40 months. CONCLUSIONS Children with cerebral palsy and hypotonia of the upper airway may achieve relief of their chronic airway obstruction following distraction osteogenesis of the mandible. Appropriate selection criteria must be adhered to, including demonstration of tongue base obstruction on flexible laryngoscopy.
Rituximab in non‐haematological disorders of adults and its mode of action

Rituximab is currently licenced for the treatment of CD20 positive lymphoma and rheumatoid arthritis (RA), however, it is increasingly being used off‐label in a wide variety of non‐haematological conditions. Although there are limited numbers of randomised controlled trials, there is a growing body of evidence for its efficacy in rheumatology, renal disease, solid organ transplantation, neuromuscular disorders, skin and endocrine disorders. The mechanism of action of rituximab in these conditions is not always clear and is likely to be via modification of both B and T cell function. Rituximab appears to be well tolerated in most groups of patients but certain side effects may be more prominent in particular conditions. This review examines the evidence base behind the use of rituximab in non‐haematological conditions in adults and any special considerations that need to be taken into account when treating particular disease groups.
Formulation of a Fast-Dissolving Ketoprofen Tablet Using Freeze-Drying in Blisters Technique

ABSTRACT The aim of this work was to develop a ketoprofen tablet which dissolve-rapidly in the mouth, therefore, needing not be swallowed. The solubility and dissolution rate of poorly water-soluble ketoprofen was improved by preparing a lyophilized tablet (LT) of ketoprofen using freeze-drying technique. The LT was prepared by dispersing the drug in an aqueous solution of highly water-soluble carrier materials consisting of gelatin, glycine, and sorbitol. The mixture was dosed into the pockets of blister packs and then was subjected to freezing and lyophilization. The saturation solubility and dissolution characteristics of ketoprofen from the LT were investigated and compared to the plain drug and the physical mixture (PM). Results obtained showed that the increase in solubility of ketoprofen from LT matrix, nearly three times greater than the solubility of the plain drug, was due to supersaturation generated by amorphous form of the drug. Results obtained from dissolution studies showed that LT of ketoprofen significantly improved the dissolution rate of the drug compared with the PM and the plain drug. More than 95% of ketoprofen in LT dissolved within 5 min compared to only 45% of ketoprofen plain drug dissolved during 60 min. Initial dissolution rate of ketoprofen in LT was almost tenfold higher than that of ketoprofen powder alone. Crystalline state evaluation of ketoprofen in LT was conducted through differential scanning calorimetry (DCS) and x-ray powder diffraction (XRPD) to denote eventual transformation to amorphous state during the process. Scanning electron microscopic (SEM) analysis was performed and results suggest reduction in ketoprofen particle size.
Remote ischemic preconditioning protects the kidney against injury after ischemia and reperfusion through activation of hypoxia-inducible factor 1

Clinical studies suggest that remote ischemic preconditioning (RIPC) in the arm or leg may protect the heart, brain and kidney against injury after ischemia and reperfusion. However, the detailed mechanism remains unclear. A recent study indicates that Hypoxia-Inducible Factor 1 (HIF-1) activates IL-10 gene transcription and is required for remote ischemic preconditioning of the heart. In this study, we investigate the role of HIF-1 in the protection effect of RIPC in the kidney after ischemia and reperfusion injury (IRI). RIPC was induced by blocking unilateral femoral artery for 5 min followed by 5 min of reperfusion for a total of five cycles. IRI was induced by blocking bilateral renal artery for 45 min followed by 120 min of reperfusion. The HIF specific inhibitor YC-1 was injected through tail vein with the dose of 2 mg/kg before surgery operation. Results showed that renal functions including serum creatinine, cystatin C and tubular injury score after IRI in rats with RIPC pretreatment were significantly better than in those without RIPC treatment. Renal expression of SOD and p-AKT were also elevated after RIPC. Our study also showed that RIPC treatment itself obviously induced the accumulation of HIF-1 in rat renal tubular epithelial nucleus and further induced upregulation of mRNA levels of target genes of HIF, such as EPO, VEGF and HO-1. Taken together, these data indicate that the protective effect of RIPC against IRI might be achieved through the activation of HIF.
Pediatric Mandibular Fractures

Over the last 20 years, a revolution in the management of facial fractures has taken place. Refinements in biocompatible materials of great delicacy and strength along with advances in our understanding of biomechanics of the face, have rendered complex injuries consistently amenable to accurate 3-dimensional reconstruction. Furthermore, with the availability of education in the techniques of internal rigid fixation, these advanced techniques have become routine practice in adults. However, the suitability of rigid internal fixation for children remains controversial. There are many concerns about the effect of implanted hardware in the mandible of a growing child. In addition, some evidence suggests that the elevation of functional matrix off of bone may result in alterations in development. The goal is to restore the underlying bony architecture to its pre-injury position in a stable fashion, with a minimal of aesthetic and functional impairment. However, in children the treatment of bony injuries is most easily accomplished by techniques that may adversely effect craniofacial development. While it is not entirely possible to resolve this dilemma, there exists an extensive body of experimental and clinical information on the appropriate management of pediatric mandibular fractures which can be used to formulate a rational treatment plan for most cases. This paper presents an overview of the contemporary understanding and application of these treatment principles.
Hts, the Drosophila homologue of adducin, physically interacts with the transmembrane receptor golden goal to guide photoreceptor axons

Neurons steer their axons towards their proper targets during development. Molecularly, a number of guidance receptors have been identified. The transmembrane protein Golden goal (Gogo) was reported previously to guide photoreceptor (R) axons in the Drosophila visual system. Here, we show that Hts, the Drosophila homologue of Adducin, physically interacts with Gogo's cytoplasmic domain via its head‐neck domain. hts null mutants show similar defects in R axon guidance as do gogo mutants. Rescue experiments suggest that the C‐terminal tail but not the MARCKS homology domain of Hts is required. Overexpression of either gogo or hts causes abnormally thick swellings of R8 axons in the medulla, but if both are co‐overexpressed, R8 axons appear normal and the amount of excessive Hts is reduced. Our results fit with a model where Gogo both positively and negatively regulates Hts that affects the Actin‐Spectrin cytoskeleton in growth cone filopodia, thereby guiding R axons. Developmental Dynamics, 2011. © 2010 Wiley‐Liss, Inc.
Morphology and physiology of abdominal projection interneurones in the locust with mechanosensory inputs from ovipositor hair receptors

The anatomy and physiological properties of eight non‐giant projection interneurones which originate from the locust terminal abdominal ganglion and receive wind and tactile inputs from ovipositor hair receptors are described. Their cell bodies (diameter 25–40 μm) are clustered in the anterolateral region of the eighth abdominal neuromere, and their axons ascend through either the contralateral or the ipsilateral connective to more anterior abdominal ganglia. In contrast to the giant interneurones, they have small‐diameter axons and are not sensitive to cercal hair wind inputs. According to their arborisation pattern within the terminal abdominal ganglion, the non‐giant projection interneurones can be divided into those with main central arborisations in the ventral neuropil (anterolateral interneurones 1–6, ALIN1–ALIN6) and those with arborisations in the dorsal neuropil (ALIN7 and ALIN8). Interneurones of the first type possess four to six secondary neurites, which form a dense dendritic field in the ventral neuropil, either contralaterally or ipsilaterally to their soma. Two interneurones have contralaterally ascending axons and main dendritic fields contralateral to their soma. Two interneurones have contralaterally ascending axons and ipsilateral main dendritic fields. One interneurone has an ipsilaterally ascending axon and an ipsilateral main dendritic field. The primary neurites of interneurones with contralateral axons transverse the ganglion through dorsal commissure 1. Five interneurones have unilateral ventral dendritic fields. One interneurone posseses bilateral ventral branches. Some interneurones project only in the eighth abdominal neuromere, whereas others send branches posteriorly into the neuropil of the ninth abdominal neuromere. Interneurones of the second type send three to four secondary neurites to the dorsal neuropil of the eighth and ninth abdominal neuromeres. One interneurone has an ascending axon in the ipsilateral connective and the other in the contralateral connective. The axons of the projection interneurones pass through a lateral or dorsal tract to the seventh abdominal ganglion. Their axonal projections are sparse, remain ipsilateral to the axons, and are confined to the dorsomedial neuropil. ALIN1‐ALIN7 are depolarised and spike in response to wind and direct mechanical deflection of trichoid sensilla on both left and right ovipositor valves. They respond with more spikes to stimulation of hairs on the ventral valve ipsilateral to their main dendritic field. ALIN8, in contrast, shows a delayed inhibitory/excitatory response. © 1996 Wiley‐Liss, Inc.