Identification of circulating biomarkers for differentiating patients with papillary thyroid cancers from benign thyroid tumors.

BACKGROUND: This study aimed to identify the potential circulating biomarkers of protein, mRNAs, and long non-coding RNAs (lncRNAs) to differentiate the papillary thyroid cancers from benign thyroid tumors. METHODS: The study population of 100 patients was classified into identification (10 patients with papillary thyroid cancers and 10 patients with benign thyroid tumors) and validation groups (45 patients with papillary thyroid cancers and 35 patients with benign thyroid tumors). The Sengenics Immunome Protein Array-combined data mining approach using the Open Targets Platform was used to identify the putative protein biomarkers, and their expression validated using the enzyme-linked immunosorbent assay. Next-generation sequencing by Illumina HiSeq was used for the detection of dysregulated mRNAs and lncRNAs. The website Timer v2.0 helped identify the putative mRNA biomarkers, which were significantly over-expressed in papillary thyroid cancers than in adjacent normal thyroid tissue. The mRNA and lncRNA biomarker expression was validated by a real-time polymerase chain reaction. RESULTS: Although putative protein and mRNA biomarkers have been identified, their serum expression could not be confirmed in the validation cohorts. In addition, seven lncRNAs (TCONS_00516490, TCONS_00336559, TCONS_00311568, TCONS_00321917, TCONS_00336522, TCONS_00282483, and TCONS_00494326) were identified and validated as significantly downregulated in patients with papillary thyroid cancers compared to those with benign thyroid tumors. These seven lncRNAs showed moderate accuracy based on the area under the curve (AUC = 0.736) of receiver operating characteristic in predicting the occurrence of papillary thyroid cancers. CONCLUSIONS: We identified seven downregulated circulating lncRNAs with the potential for predicting the occurrence of papillary thyroid cancers.

Impact failure in two silicates revealed by ultrafast, in situ, synchrotron X-ray microscopy.

To travel safely behind screens that can protect us from stones and hail, we must understand the response of glass to impact. However, without a means to observe the mechanisms that fail different silicate architectures, engineering has relied on external sensors, post-impact examination and best-guess to glaze our vehicles. We have used single and multi-bunch, X-ray imaging to differentiate distinct phases of failure in two silicates. We identified distinct micromechanisms, operating in tandem and leading to failure in borosilicate glass and Z-cut quartz. A surface zone in the amorphous glass densifies before bulk fracture occurs and then fails the block, whilst in quartz, fast cracks, driven down cleavage planes, fails the bulk. Varying the rate at which ejecta escapes by using different indenter tip geometries controls the failed target's bulk strength. This opens the way to more physically based constitutive descriptions for the glasses allowing design of safer, composite panels by controlling the impulses felt by protective screens.

Phase-contrast 3D tomography of HeLa cells grown in PLLA polymer electrospun scaffolds using synchrotron X-rays.

Advanced imaging is useful for understanding the three-dimensional (3D) growth of cells. X-ray tomography serves as a powerful noninvasive, nondestructive technique that can fulfill these purposes by providing information about cell growth within 3D platforms. There are a limited number of studies taking advantage of synchrotron X-rays, which provides a large field of view and suitable resolution to image cells within specific biomaterials. In this study, X-ray synchrotron radiation microtomography at Diamond Light Source and advanced image processing were used to investigate cellular infiltration of HeLa cells within poly L-lactide (PLLA) scaffolds. This study demonstrates that synchrotron X-rays using phase contrast is a useful method to understand the 3D growth of cells in PLLA electrospun scaffolds. Two different fiber diameter (2 and 4 µm) scaffolds with different pore sizes, grown over 2, 5 and 8 days in vitro, were examined for infiltration and cell connectivity. After performing visualization by segmentation of the cells from the fibers, the results clearly show deeper cell growth and higher cellular interconnectivity in the 4 µm fiber diameter scaffold. This indicates the potential for using such 3D technology to study cell-scaffold interactions for future medical use.

Investigating the evolving microstructure of lithium metal electrodes in 3D using X-ray computed tomography.

The growth of electrodeposited lithium microstructures on metallic lithium electrodes has prevented their use in rechargeable lithium batteries due to early performance degradation and safety implications. Understanding the evolution of lithium microstructures during battery operation is crucial for the development of an effective and safe rechargeable lithium-metal battery. This study employs both synchrotron and laboratory X-ray computed tomography to investigate the morphological evolution of the surface of metallic lithium electrodes during a single cell discharge and over numerous cycles, respectively. The formation of surface pits and the growth of mossy lithium deposits through the separator layer are characterised in three-dimensions. This has provided insight into the microstructural evolution of lithium-metal electrodes during rechargeable battery operation, and further understanding of the importance of separator architecture in mitigating lithium dendrite growth.

B-cell lymphoma/leukemia 10 promotes oral cancer progression through STAT1/ATF4/S100P signaling pathway.

This corrects the article DOI: 10.1038/onc.2014.43.

On compression and damage evolution in two thermoplastics.

The well-known Taylor cylinder impact test, which follows the impact of a flat-ended cylindrical rod onto a rigid stationary anvil, is conducted over a range of impact speeds for two polymers, polytetrafluoroethylene (PTFE) and polyetheretherketone (PEEK). In previous work, experiments and a model were developed to capture the deformation behaviour of the cylinder after impact. These works showed a region in which spatial and temporal variation of both longitudinal and radial deformation provided evidence of changes in phase within the material. In this further series of experiments, this region is imaged in a range of impacted targets at the Diamond synchrotron. Further techniques were fielded to resolve compressed regions within the recovered polymer cylinders that showed a fracture zone in the impact region. The combination of macroscopic high-speed photography and three-dimensional X-ray imaging has identified the development of failure with these polymers and shown that there is no abrupt transition in behaviours but rather a continuous range of responses to competing operating mechanisms. The behaviours noted in PEEK in these polymers show critical gaps in understanding of polymer high strain-rate response.

Plasmakristall-4: New complex (dusty) plasma laboratory on board the International Space Station.

New complex-plasma facility, Plasmakristall-4 (PK-4), has been recently commissioned on board the International Space Station. In complex plasmas, the subsystem of µm-sized microparticles immersed in low-pressure weakly ionized gas-discharge plasmas becomes strongly coupled due to the high (103-104 e) electric charge on the microparticle surface. The microparticle subsystem of complex plasmas is available for the observation at the kinetic level, which makes complex plasmas appropriate for particle-resolved modeling of classical condensed matter phenomena. The main purpose of PK-4 is the investigation of flowing complex plasmas. To generate plasma, PK-4 makes use of a classical dc discharge in a glass tube, whose polarity can be switched with the frequency of the order of 100 Hz. This frequency is high enough not to be felt by the relatively heavy microparticles. The duty cycle of the polarity switching can be also varied allowing to vary the drift velocity of the microparticles and (when necessary) to trap them. The facility is equipped with two videocameras and illumination laser for the microparticle imaging, kaleidoscopic plasma glow observation system and minispectrometer for plasma diagnostics and various microparticle manipulation devices (e.g., powerful manipulation laser). Scientific experiments are programmed in the form of scripts written with the help of specially developed C scripting language libraries. PK-4 is mainly operated from the ground (control center CADMOS in Toulouse, France) with the support of the space station crew. Data recorded during the experiments are later on delivered to the ground on the removable hard disk drives and distributed to participating scientists for the detailed analysis.

Pushing the limits: an instrument for hard X-ray imaging below 20 nm.

Hard X-ray microscopy is a prominent tool suitable for nanoscale-resolution non-destructive imaging of various materials used in different areas of science and technology. With an ongoing effort to push the 2D/3D imaging resolution down to 10 nm in the hard X-ray regime, both the fabrication of nano-focusing optics and the stability of the microscope using those optics become extremely challenging. In this work a microscopy system designed and constructed to accommodate multilayer Laue lenses as nanofocusing optics is presented. The developed apparatus has been thoroughly characterized in terms of resolution and stability followed by imaging experiments at a synchrotron facility. Drift rates of ∼2 nm h(-1) accompanied by 13 nm × 33 nm imaging resolution at 11.8 keV are reported.

B-cell lymphoma/leukemia 10 promotes oral cancer progression through STAT1/ATF4/S100P signaling pathway.

B-cell lymphoma/leukemia 10 (BCL10) is an apoptotic regulatory protein related to advanced TNM stage and disease recurrence in oral squamous cell carcinoma (OSCC). However, the regulatory mechanism of BCL10 in OSCC progression is still unknown. Here, we showed that knockdown of endogenous BCL10 could significantly reduce cell migration and invasion abilities, retard cell proliferation by G0/G1 phase accumulation and inhibit tumorigenicity in vivo. In molecular level, we identified S100P as a crucial downstream effector of BCL10-inhibited OSCC progression by high-throughput microarray analysis. S100P messenger RNA and protein expression levels were significantly diminished in silenced-BCL10 clones, and transfected S100P expression plasmids restored migration, invasion, proliferation abilities and tumorigenicity in shBCL10 transfectants. Furthermore, we provided evidence that BCL10 regulated S100P expression through signal transducers and activators of transcription 1 (STAT1) and activating transcription factor 4 (ATF4). Knockdown of BCL10 decreased S100P promoter activity, but showed no effect in truncated STAT1/ATF4 S100P promoter.  In addition, we also found that the P50/P65 signaling pathway was involved in BCL10-enhanced OSCC progression. Restored S100P in silenced-BCL10 clones could markedly reverse P65 activation via outside-in signaling. Taken together, we discovered a novel axis of BCL10-regulated OSCC progression via STAT1/ATF4/S100P/P65 signaling, which could predict the prognosis of OSCC and will be beneficial for developing therapeutic strategy against advanced OSCC.

Laparoscopic omega-loop gastric bypass for the conversion of failed sleeve gastrectomy: early experience.

OBJECTIVES: Despite the initial effectiveness of sleeve gastrectomy (SG), some patients who undergo this purely restrictive technique have inadequate weight loss or renewed weight gain and persistent obesity-related co-morbidities with their potentially lethal complications. In such patients, the conversion of SG by the addition of a malabsorptive technique may then be necessary. PATIENTS AND METHODS: Conversion of SG to a mini gastric bypass (MGBP) was evaluated for failure of weight loss. An ante-colic end-to-side stapled gastro-jejunal anastomosis was performed laparoscopically, connecting the long narrow gastric tube to the jejunum at a point 200cm downstream from the ligament of Treitz. RESULTS: Between October 2006 and February 2012, 651 laparoscopic MGBP were performed for morbid obesity. Twenty-three of these patients (3.5%) had previously undergone SG. The conversion from SG to MGPB was performed laparoscopically in 19 of the 23 patients (81%) at a mean interval of 26.3months (8.2-63.7). The 30-day postoperative mortality rate was zero and the morbidity rate was 9.5%. The mean BMI before MGBP was 44±7.7kg (35.8-55.4). Conversion of SG to MGBP resulted in additional weight loss, achieving a mean BMI of 39.9 with a 26.8% loss of excess BMI (EBL) at 3months, mean BMI of 36.5 with 37.2% EBL at 12months, mean BMI of 36.2 with 48.6% EBL at 18months, and mean BMI of 35.7 with EBL of 51.6% at 24months. The overall mean EBL was 57.3±19.5% (range: 25-82%) at 42.3months (range 16.7-60.8months). CONCLUSION: Conversion of SG to MGBP is feasible, safe and effective, and results in significant additional weight loss. Definitive results at 2 and 5years are awaited for the long-term procedure validation.

X-ray phase-contrast imaging with nanoradian angular resolution.

We present a new quantitative x-ray phase-contrast imaging method based on the edge illumination principle, which allows achieving unprecedented nanoradian sensitivity. The extremely high angular resolution is demonstrated theoretically and through experimental images obtained at two different synchrotron radiation facilities. The results, achieved at both very high and very low x-ray energies, show that this highly sensitive technique can be efficiently exploited over a very broad range of experimental conditions. This method can open the way to new, previously inaccessible scientific applications in various fields including biology, medicine and materials science.

Performance and characterization of the prototype nm-scale spatial resolution scanning multilayer Laue lenses microscope.

Synchrotron based x-ray microscopy established itself as a prominent tool for noninvasive investigations in many areas of science and technology. Many facilities around the world routinely achieve sub-micrometer resolution with a few instruments capable of imaging with the spatial resolution better than 100 nm. With an ongoing effort to push the 2D/3D resolution down to 10 nm in the hard x-ray regime both fabrication of the nano-focusing optics and stability of a microscope become extremely challenging. In this work we present our approach to overcome technical challenges on the path towards high spatial resolution hard x-ray microscopy and demonstrate the performance of a scanning fluorescence microscope equipped with the multilayer Laue lenses focusing optics.

[Agreement between observers with different experience in the interpretation of the stress myocardial perfusion electrocardiogram in SPECT]. / Concordancia entre observadores con distinta experiencia en interpretación de electrocardiograma de esfuerzo en SPECT de perfusión miocárdica.

UNLABELLED: Coronary artery disease (CAD) is the leading cause of death in many countries. Stress electrocardiogram (ECG) is able to detect myocardial ischemia and also has prognostic value, which may be impaired in presence of electrical baseline abnormalities. Stress myocardial single photon emission tomography (SPECT) has recognized utility yield in assessment of CAD, requiring independent interpretation of ECG and myocardial images. PURPOSE: To analyze stress ECG interpretation reproducibility among observers with different training level, including pre- and post-graduate medical students, compared to an experienced cardiologist and also with SPECT. METHOD: We studied 95 patients under CAD evaluation, mean age 61+/-9.3 years (range: 42-85), 56% male. Interobserver correlation kappa (k) between perfusion gated (99m)Tc-Sestamibi SPECT and exercise ECG were calculated as normal/abnormal, presence of necrosis, ischemia or mixed pattern. Interobserver kappa (k) analysis was made. RESULTS: 49.5% stress ECG and 45% SPECT studies were abnormal at the initial report with 62.1% concordance (k: 0.24) for normal/abnormal and 58.9% for ischemia (k: 0.14). Agreement between stress ECG initial report and independent cardiologist was 89.5% (k: 0.78). The correlation between independent observers and the initial report ranged between 62.1% and 48.4%, for baseline ECG between 41.1% and 90.5% considering normal/abnormal, and between 80% and 93.7% (k: 0.59-0.87) for the presence of ischemia. CONCLUSION: Stress ECG interpretation presented adequate interobserver reproducibility with greater agreement in the most experienced observers, confirming the importance of training.

Concordancia entre observadores con distinta experiencia en interpretación de electrocardiograma de esfuerzo en SPECT de perfusión miocárdica / Agreement between observers with different experience in the interpretation of the stress myocardial perfusion electrocardiogram in SPECT

ResumenLa enfermedad coronaria (EC) es la principal causa de muerte en muchos países. El electrocardiograma (ECG) de esfuerzo permite evaluar la isquemia miocárdica y agrega valor pronóstico, con rendimiento limitado en presencia de alteraciones eléctricas basales. La SPECT (single photon emission computed tomography ‘tomografía computarizada por emisión de fotón único’) en esfuerzo se utiliza para evaluación de EC, con reconocido buen rendimiento, que requiere interpretación independiente del ECG y de las imágenes miocárdicas.ObjetivoAnalizar la concordancia en la interpretación del ECG de esfuerzo entre observadores en entrenamiento, incluyendo alumnos de pre y posgrado de Medicina, con un cardiólogo experimentado y con SPECT miocárdica.MétodoSe incluyeron 95 pacientes enviados para evaluación de EC, edad: 61 ± 9,3 años (rango: 42–85), 56%: hombres. Se calculó la concordancia entre la SPECT de perfusión sincronizada con 99mTc-Sestamibi y ECG de esfuerzo según resultado normal/anormal, necrosis, isquemia o patrón mixto. Se efectuó un análisis interobservador kappa (k).ResultadosFueron anormales el 49,5% de los ECG de esfuerzo según informe inicial y el 45% de los estudios SPECT; la concordancia para normal/anormal fue del 62,1% (κ: 0,24) y para isquemia del 58,9% (κ: 0,14). La concordancia entre informe ECG de esfuerzo inicial y el del cardiólogo independiente fue del 89,5% (κ: 0,78). Las concordancias interobservador con este informe variaron entre el 62,1 y el 48,4%; para ECG basal, entre el 41,1 y el 90,5% considerando normal/anormal; y entre el 80 y el 93,7% (κ: 0,59–0,87) para isquemia entre éste y otros observadores.ConclusiónEn la interpretación del ECG de esfuerzo se encontró adecuada reproducibilidad entre observadores, con mayor acuerdo en los más experimentados, lo que confirma la importancia del entrenamiento(AU9

AbstractCoronary artery disease (CAD) is the leading cause of death in many countries. Stress electrocardiogram (ECG) is able to detect myocardial ischemia and also has prognostic value, which may be impaired in presence of electrical baseline abnormalities. Stress myocardial single photon emission tomography (SPECT) has recognized utility yield in assessment of CAD, requiring independent interpretation of ECG and myocardial images.PurposeTo analyze stress ECG interpretation reproducibility among observers with different training level, including pre- and post-graduate medical students, compared to an experienced cardiologist and also with SPECT.MethodWe studied 95 patients under CAD evaluation, mean age 61±9.3 years (range: 42–85), 56% male. Interobserver correlation kappa (k) between perfusion gated 99mTc-Sestamibi SPECT and exercise ECG were calculated as normal/abnormal, presence of necrosis, ischemia or mixed pattern. Interobserver kappa (k) analysis was made.Results49.5% stress ECG and 45% SPECT studies were abnormal at the initial report with 62.1% concordance (k: 0.24) for normal/abnormal and 58.9% for ischemia (k: 0.14). Agreement between stress ECG initial report and independent cardiologist was 89.5% (k: 0.78). The correlation between independent observers and the initial report ranged between 62.1% and 48.4%, for baseline ECG between 41.1% and 90.5% considering normal/abnormal, and between 80% and 93.7% (k: 0.59–0.87) for the presence of ischemia.ConclusionStress ECG interpretation presented adequate interobserver reproducibility with greater agreement in the most experienced observers, confirming the importance of training(AU)

[Total knee arthroplasty - GPs' views in Germany: a questionnaire-based study]. / Beurteilung des Verfahrens der Knieendoprothetik durch deutsche Hausärzte: Eine Fragebogenstudie.

To assess general knowledge and individual views of general practitioners (GPs) on total knee arthroplasty (TKA), we conducted a questionnaire-based survey involving 170 GPs in Germany. Eighty-one GPs returned the questionnaire. They treat a mean of 10.6+/-8.3 patients with TKA. General knowledge can be estimated as good. Compared with the data in the literature, GPs assessed the rate of satisfied patients as lower and the risk for revision surgery as higher. The mean risk of potential complications (infection, instability, persistent pain) in association with TKA was estimated correctly. Seventy-eight percent of GPs consider an allergic reaction to the implant or bone cement as problematic. The number of cases per year, personal experience with the surgeon, and - less important - local accessibility are important factors for GPs when recommending an operating centre to a patient.A broad spectrum of individual responses indicates the need to improve the information transfer between orthopaedic surgeons and referring GPs.

[Metal sensitivity in patients with joint replacement arthroplasties before and after surgery]. / Metallallergie bei Patienten vor bzw. nach endoprothetischem Gelenkersatz.

The object of the present study was to determine the incidence of metal sensitivity in patients with joint replacement arthroplasties before and after surgery and whether this is of significance as regards the final outcome of the operative procedure. A questionnaire-based survey involved 1,335 patients with an average age of 61 years and joint replacement arthroplasties before and after surgery. A history of dermal sensitivity to metal was given in 99 (7%) patients with almost equal frequency in the pre- and postoperative groups (7.6 vs 7.2%). In only 27 of 99 cases was the metal sensitivity recorded in the patient chart. In 46 cases investigation was done after knee or hip replacement arthroplasty with an average implant time in situ of 68 months. In 32 of 46 patients a sensitivity to the implanted material was known and they did not show any complications related to the metal sensitivity.It is currently unclear whether metal sensitivity could be induced by joint replacement arthroplasties and it remains uncertain whether loosening or infection causes the sensitization as a consequence of increased release of metal ions or vice versa. To draw further conclusions considerably more detailed studies involving more patients are clearly indicated.

[Headache after a stay in the Dominican Republic]. / Kopfschmerzen nach Aufenthalt in der Dominikanischen Republik.

CASE HISTORY: In a 27-year-old female German patient severe headache and wandering paresthesias appeared one week after returning from a holiday in the Dominican Republic. After 3 weeks of ongoing symptoms she was admitted to our hospital with the suspicion of an inflammatory or infectious disease of the central nervous system. Upon admission slight stiffness of the neck, fever (38.2 C) and paresthesias of the right elbow and the right thigh were noticed. LABORATORY FINDINGS: Cerebrospinal fluid (CSF) revealed an eosinophilic pleocytosis. In the acute phase of the disease, antibodies against nematodes were found in CSF, without corresponding antibody-reactivity in serum. In the course levels of nematode antibodies in CSF increased and antibody-reactivity in serum was observed. Thorough investigation for other infectious or inflammatory causes of eosinophilic meningitis revealed no abnormalities. DIAGNOSIS, TREATMENT AND COURSE: Symptoms, onset within the typical incubation period and the eosinophilic meningitis lead to the diagnosis of a suspected Angiostrongyliasis. Successful treatment was achieved with a combination of oral albendazole and corticosteroids given for 4 weeks. CONCLUSION: Infection with larvae of Angiostrongylus cantonensis is one of the main causes of eosinophilic meningitis worldwide. Human infection can occur after ingestion of intermediate hosts or contaminated vegetables. Angiostrongyliasis has been endemic to Southeast Asia and the Pacific Basin and only recently cases from the Caribbean have been described. Headache, paresthesias and the finding of an eosinophilic meningitis in patients returning from tropical or subtropical regions should lead to the suspicion and eventually the treatment of an Angiostrongyliasis.

Visualizing soft tissue in the mammalian cochlea with coherent hard X-rays.

This paper concerns an important aspect of current developments in medical and biological imaging: the possibility for imaging soft tissue at relatively high resolution in the micrometer range or better, without tedious and/or entirely destructive sample preparation. Structures with low absorption contrast have been visualized using in-line phase contrast imaging. The experiments have been performed at the Advanced Photon Source, a third generation source of synchrotron radiation. The source provides highly coherent X-ray radiation with high photon flux (>10(14) photons/s) at high photon energies (5-70 keV). Thick gerbil cochlear slices have been imaged and were compared with those obtained by light microscopy. Furthermore, intact gerbil cochleae have been imaged to identify the soft tissue structures involved in the hearing process. The present experimental approach was essential for visualizing the inner ear structures involved in the hearing process in an intact cochlea.