julilili42/papers huggingface dataset:
Trimodal therapy for muscle-invasive bladder cancer
2018-10-16

Radical cystectomy is the standard therapy for patients with muscle-invasive bladder cancer. Organ-preserving surgical procedures have been established as alternatives to radical surgery for localized malignancies in other anatomic sites. Trimodal therapy consisting of radiation therapy, chemotherapy, and either transurethral resection of the bladder or partial cystectomy is an effective treatment for selected patients with muscle-invasive bladder cancer that allows for preservation of the urinary bladder. Areas covered: This review provides an overview of the value of trimodal therapy in the treatment of muscle-invasive bladder cancer. Expert commentary: Prerequisites for trimodal therapy for bladder cancer include: good bladder function, unifocal cT2 urothelial carcinoma of the bladder, and absence of hydronephrosis. Careful selection of patients and accurate assessment of the anatomic extent of the tumor is important for patient safety. The basis for successful trimodal therapy is complete transurethral resection of the tumor, followed by radiation therapy with concurrent radiosensitizing chemotherapy. Cystoscopic controls and follow-up biopsies should be performed at completion of adjuvant therapy or shortly after induction of trimodal therapy to identify nonresponders for whom salvage radical cystectomy may be indicated.
Overlooking
2018-10-16

The cognitive processes that underly expert decision making in medical image interpretation are crucial to the understanding of what constitutes optimal performance. Often, if an anomaly goes undetected, the exact nature of the false negative is not fully understood. This work looks at 24 experts' performance (true positives and false negatives) during an anomaly detection task for 13 images and the corresponding gaze behavior. By using a drawing and an eye-tracking experimental paradigm, we compared expert target anomaly detection in orthopantomographs (OPTs) against their own gaze behavior. We found there was a relationship between the number of anomalies detected and the anomalies looked at. However, roughly 70% of anomalies that were not explicitly marked in the drawing paradigm were looked at. Therefore, we looked how often an anomaly was glanced at. We found that when not explicitly marked, target anomalies were more often glanced at once or twice. In contrast, when targets were marked, the number of glances was higher. Furthermore, since this behavior was not similar over all images, we attribute these differences to image complexity.
Investigation of the influence of macromolecules and spline baseline in the fitting model of human brain spectra at 9.4T
2018-10-17

Purpose In this study, the influence of experimentally measured macromolecules and spline baseline on the quantification results of proton MRS data was investigated. Methods Proton MRS spectra from the left parietal lobe and the occipital lobe were acquired at 9.4T in the human brain using metabolite‐cycled semi‐LASER. Then, the left parietal lobe data, along with the occipital lobe, spectra were quantified and the influence of the inclusion of experimentally measured macromolecular basis sets in the fitting model was evaluated. Furthermore, the effect of the stiffness of the fitted spline baselines on the resulting metabolite concentrations was evaluated. Results In general, concentrations were higher for metabolites in occipital lobe than the left parietal lobe. The inclusion of an experimentally acquired measured macromolecular basis set from another brain region neither affected the quantification results nor the resulting spline baselines significantly. A highly flexible spline baseline led to overestimation or underestimation of metabolite concentrations. Differences of above 15% in the quantification of metabolite levels for both lobes were observed for several metabolites using LCModel default settings for spline baselines and macromolecules in comparison to stiffer spline baselines. Conclusion Fitting with the default LCModel macromolecular basis set and spline baseline model had significant influence in the resulting spline baselines, leading to large deviations both in the concentrations and fitted macromolecular components. The number of knots in the spline may create overflexible baselines, which can potentially lead to quantification errors. Interestingly, the interchange of macromolecular basis set between occipital lobe and left parietal lobe spectra had less influence on the quantification results compared to the default LCModel settings.
First core properties: from low- to high-mass star formation
2018-10-17

\\nAims. In this study, the main goal is to understand the molecular cloud core collapse through the stages of first and second hydrostatic core formation. We investigate the properties of Larsons first and second cores following the evolution of the molecular cloud core until the formation of Larson’s cores. We expand these collapse studies for the first time to span a wide range of initial cloud masses from 0.5 to 100 M⊙.\\nMethods. Understanding the complexity of the numerous physical processes involved in the very early stages of star formation requires detailed thermodynamical modelling in terms of radiation transport and phase transitions. For this we used a realistic gas equation of state via a density- and temperature-dependent adiabatic index and mean molecular weight to model the phase transitions. We used a grey treatment of radiative transfer coupled with hydrodynamics to simulate Larsons collapse in spherical symmetry.\\nResults. We reveal a dependence of a variety of first core properties on the initial cloud mass. The first core radius and mass increase from the low-mass to intermediate-mass regime and decrease from the intermediate-mass to high-mass regime. The lifetime of first cores strongly decreases towards the intermediate- and high-mass regimes.\\nConclusions. Our studies show the presence of a transition region in the intermediate-mass regime. Low-mass protostars tend to evolve through two distinct stages of formation that are related to the first and second hydrostatic cores. In contrast, in the high-mass star formation regime, collapsing cloud cores rapidly evolve through the first collapse phase and essentially immediately form Larson’s second cores.\\n
Perisaccadic perceptual mislocalization is different for upward saccades
2018-10-17

Saccadic eye movements, which dramatically alter retinal images, are associated with robust perimovement perceptual alterations. Such alterations, thought to reflect brain mechanisms for maintaining perceptual stability in the face of saccade-induced retinal image disruptions, are often studied by asking subjects to localize brief stimuli presented around the time of horizontal saccades. However, other saccade directions are not usually explored. Motivated by recently discovered asymmetries in upper and lower visual field representations in the superior colliculus, a structure important for both saccade generation and visual analysis, we observed significant differences in perisaccadic perceptual alterations for upward saccades relative to other saccade directions. We also found that, even for purely horizontal saccades, perceptual alterations differ for upper vs. lower retinotopic stimulus locations. Our results, coupled with conceptual modeling, suggest that perisaccadic perceptual alterations might critically depend on neural circuits, such as superior colliculus, that asymmetrically represent the upper and lower visual fields. NEW &amp; NOTEWORTHY Brief visual stimuli are robustly mislocalized around the time of saccades. Such mislocalization is thought to arise because oculomotor and visual neural maps distort space through foveal magnification. However, other neural asymmetries, such as upper visual field magnification in the superior colliculus, may also exist, raising the possibility that interactions between saccades and visual stimuli would depend on saccade direction. We confirmed this behaviorally by exploring and characterizing perisaccadic perception for upward saccades.
Is Bone Elevation in Hand Muscle Attachments Associated with Biomechanical Stress? A Histological Approach to an Anthropological Question
2018-10-17

ABSTRACT In anthropological sciences, muscle attachments are typically utilized for reconstructing the physical activities of past human populations. This approach relies on the concept that entheseal bone morphology is influenced by cumulative biomechanical stress. A fundamental criterion for assessing the stage of entheseal change involves the proportion of elevated bone area. However, it is not yet clear if bone elevation is associated with biomechanical forces exerted during physical activity, while the histology of the entheses of the human hand, the least‐bodyweight‐bearing anatomical area, is not fully investigated. Multiple previous studies on entheses have concluded that the concentration of calcified fibrocartilage reflects the level of applied forces. On this basis, if hand entheseal surface elevation was associated with the level of biomechanical stress, then a greater amount of calcified fibrocartilage would be expected in entheses' central and more projecting bone areas. More importantly, individual entheses with a greater proportion of elevated bone areas would present a higher total concentration of calcified fibrocartilage. To test these hypotheses, this pilot study conducted a histological quantitative analysis on two thumb entheses of four fully‐documented body donors. Across individuals, all central entheseal regions presented greater calcified fibrocartilage, while the entheses showing additional bone elevation in their marginal areas comprised substantially higher total values. The observations of this small‐scale pilot study support the concept that interindividual differences in entheseal bone morphology are related to varying levels of biomechanical loading. Furthermore, they encourage future research to compile larger sample sizes, for comparing individuals with distinct lifelong activities. Anat Rec, 302:1093–1103, 2019. © 2018 Wiley Periodicals, Inc.
An empirical evaluation of multivariate lesion behaviour mapping using support vector regression
2018-10-17

Abstract Multivariate lesion behaviour mapping based on machine learning algorithms has recently been suggested to complement the methods of anatomo-behavioural approaches in cognitive neuroscience. Several studies applied and validated support vector regression-based lesion symptom mapping (SVR-LSM) to map anatomo-behavioural relations. However, this promising method, as well as the multivariate approach per se, still bears many open questions. By using large lesion samples in three simulation experiments, the present study empirically tested the validity of several methodological aspects. We found that i) correction for multiple comparisons is required in the current implementation of SVR-LSM, ii) that sample sizes of at least 100 to 120 subjects are required to optimally model voxel-wise lesion location in SVR-LSM, and iii) that SVR-LSM is susceptible to misplacement of statistical topographies along the brain’s vasculature to a similar extent as mass-univariate analyses.
The Strategic Role of Thracian Fortifications in the Balkan Wars of Late Antiquity
2018-10-17

The strategic role of Thracian cities changed across Late Antiquity thanks to major political events, which resulted in their increasing vulnerability. These events included, in particular, barbarian crossings of the Lower Danube from 376, and the gradual breakdown of the Middle Danube frontier from the late 4th century AD. The first of these developments led to larger numbers of Gothic soldiers in the Diocese of Thrace and the threat of periodic rebellions by these federate troops. The second culminated in the rise of barbarian powers in Pannonia and the Middle Danube capable of launching devastating attacks on eastern Illyricum and Thrace. Because of these military threats, larger and more numerous fortifications sprang up along the Military Highway and Via Egnatia, northern and southern routes into the Haemus Mountains, and in the province of Europa. As well as a ‘defence-in-depth’ system, this network of fortified cities and bases operated as a platform from which imperial armies could launch offensive campaigns against rebellious or invading barbarians.
Higher Substrate Ratios of Ethanol to Acetate Steered Chain Elongation towardn-Caprylate in a Bioreactor with Product Extraction
2018-10-18

Syngas fermentation to ethanol and acetate has recently been coupled to microbial chain elongation to produce medium-chain carboxylates, including n-caproate and n-caprylate. These medium-chain carboxylates are relatively hydrophobic, and thus easier to extract from solution than miscible ethanol. Here, we examined the effect of 11 different ethanol-to-acetate substrate ratios (ranging from 1.8 to 275 g COD g COD<sup>-1</sup> [1.2 to 183 mol mol<sup>-1</sup>]) on directing chain elongation toward n-caprylate in a 0.7-L upflow anaerobic filter with product extraction. During an eight-month operating period, we monitored the performance and characterized the microbiome composition of this chain-elongating bioreactor. We also developed a thermodynamic model to predict the favorability of n-caprylate production at different substrate ratios. As predicted by our model, higher ethanol-to-acetate substrate ratios fed to our bioreactor led to higher specificities for n-caprylate production. We observed that feeding primarily ethanol to the bioreactor (i.e., ethanol-to-acetate substrate ratio of 275 g COD g COD<sup>-1</sup>) resulted in the highest specificity for n-caprylate, but the n-caprylate production rate decreased at this high ratio, resulting in lower conversion efficiencies. Thus, care should be taken not to overload the system with primarily ethanol as the substrate and to lower the organic loading rate.
An unusually high substitution rate in transplant-associated BK polyomavirus in vivo is further concentrated in HLA-C-bound viral peptides
2018-10-18

Infection with human BK polyomavirus, a small double-stranded DNA virus, potentially results in severe complications in immunocompromised patients. Here, we describe the in vivo variability and evolution of the BK polyomavirus by deep sequencing. Our data reveal the highest genomic evolutionary rate described in double-stranded DNA viruses, i.e., 10(-3)-10(-5) substitutions per nucleotide site per year. High mutation rates in viruses allow their escape from immune surveillance and adaptation to new hosts. By combining mutational landscapes across viral genomes with in silico prediction of viral peptides, we demonstrate the presence of significantly more coding substitutions within predicted cognate HLA-C-bound viral peptides than outside. This finding suggests a role for HLA-C in antiviral immunity, perhaps through the action of killer cell immunoglobulin-like receptors. The present study provides a comprehensive view of viral evolution and immune escape in a DNA virus.
Periprosthetic Infection: Major Cause of Early Failure of Primary and Revision Total Knee Arthroplasty
2018-10-18

Abstract Revision total knee arthroplasty (RTKA) represents an effective treatment for failed TKA, but with less favorable outcomes. Considering the technical complexity and economic burden of RTKA procedures, it is mandatory to investigate current mechanisms and predictors for RTKA failure. The objective of this study is to evaluate the survivorship and determine the predominant causes of failure of RTKA. A total of 146 patients undergoing RTKA between 2003 and 2013 were identified from the institutional database. Revision was defined as surgery in which the whole prostheses (inlay and both femoral and tibial components) required exchange. Median follow-up was 6.3 ± 2.7 years (range: 2.2–10). Patient demographics, year of primary implantation, reasons for revision surgery, implant type, pain, knee mobility, systemic or local postoperative complications, and treatment of the complications were recorded and evaluated. Infection was a major cause of failure followed by aseptic loosening, instability, pain, malalignment, and inlay wear. Following RTKA, Knee Society Score (KSS) (knee score and functional score) demonstrated a significant improvement (p &lt; 0.05). No significant difference in flexion, extension deficit, and KSS was detected between aseptic and septic primary TKAs preoperatively and following first RTKA. Reinfection rate of the septic primary TKAs was 5%. Infection was the major cause of a second revision, reaching as high as 50% in all cases. The results of this study support that septic failure of a primary TKA is likely to occur within the first 2 years following implantation. Septic failure of primary TKA does not influence survival of the revision prosthesis.
Over‐discretized SENSE reconstruction and B0 correction for accelerated non‐lipid‐suppressed 1H FID MRSI of the human brain at 9.4 T
2018-10-18

The aim of this work was to use post‐processing methods to improve the data quality of metabolite maps acquired on the human brain at 9.4 T with accelerated acquisition schemes. This was accomplished by combining an improved sensitivity encoding (SENSE) reconstruction with a B 0 correction of spatially over‐discretized magnetic resonance spectroscopic imaging (MRSI) data. Since MRSI scans suffer from long scan duration, investigating different acceleration techniques has recently been the focus of several studies. Due to strong B 0 inhomogeneity and strict specific absorption rate (SAR) limitations at ultra‐high fields, the use of a low‐SAR sequence combined with an acceleration technique that is compatible with dynamic B 0 shim updating is preferable. Hence, in this study, a non‐lipid‐suppressed ultra‐short T E and T R 1 H free induction decay MRSI sequence is combined with an in‐plane SENSE acceleration technique to obtain high‐resolution metabolite maps in a clinically feasible scan time. One of the major issues in applying parallel imaging techniques to non‐lipid‐suppressed MRSI is the presence of strong lipid aliasing artifacts, which if not thoroughly resolved will hinder the accurate quantification of the metabolites of interest. To achieve a more robust reconstruction, an over‐discretized SENSE reconstruction (with direct control over the shape of the spatial response function) was combined with an over‐discretized B 0 correction. This method is compared with conventional SENSE reconstruction for seven acceleration schemes on four healthy volunteers. The over‐discretized method consistently outperformed conventional SENSE, resulting in an average of 23 ± 1.2% higher signal‐to‐noise ratio and 8 ± 2.9% less error in the fitting of the N‐acetylaspartate signal over a whole brain slice. The highest achievable acceleration factor with the proposed technique was determined to be 4. Finally, using the over‐discretized method, high‐resolution (97 μL nominal voxel size) metabolite maps can be acquired in 3.75 min at 9.4 T. This enables the acquisition of high‐resolution metabolite maps with more spatial coverage at ultra‐high fields.
Halides of the Heavier Group 14 Homologues Germanium, Tin, and Lead—A Journey through Unusual Compounds and Oxidation States
2018-10-18

Abstract Classical halides of the heavier Group 14 homologues germanium, tin, and lead are common precursors for the synthesis of exciting compounds, such as polyhedral clusters. To get access to larger metalloid cluster compounds of Group 14, the disproportionation reaction of metastable monohalide solutions, accessible through a preparative co‐condensation reaction, proved to be quite successful. As the identity of the subvalent halides within the metastable solutions were yet unknown the reaction course from a monohalide precursor to a metalloid cluster was mostly unidentified. This might change now, as a first subhalide cluster [Ge 14 Br 8 (Et 3 P) 4 ] could be characterized, being the first trapped intermediate of the disproportionation reaction of Group 14 subhalides. All these aspects are included within this Minireview, together with a short historical overview, dealing with the development of the preparative co‐condensation technique out of the matrix isolation technique, being the essential first step of the synthesis of metastable monohalide solutions of the heavier Group 14 elements Ge and Sn.
t(14;18)-positive B cells: is it seed or soil?
2018-10-18

In this issue of Blood, Hellmuth et al provide new insights into the molecular genetic profile of duodenal-type follicular lymphoma (FL), with comparisons to both typical advanced-stage nodal FL and a lesser number of cases of FL with limited stage disease.1
Scanning Fluorescence Correlation Spectroscopy for Quantification of the Dynamics and Interactions in Tube Organelles of Living Cells
2018-10-18

Abstract Single‐molecule spectroscopic quantification of protein‐protein interactions directly in the organelles of living cells is highly desirable but remains challenging. Bulk methods, such as Förster resonance energy transfer (FRET), currently only give a relative quantification of the strength of protein‐protein interactions. Here, we introduce tube scanning fluorescence cross‐correlation spectroscopy (tubeSFCCS) for the absolute quantification of diffusion and complex formation of fluorescently labeled molecules in the mitochondrial compartments. We determined the extent of association between the apoptosis regulators Bcl‐xL and tBid at the mitochondrial outer membrane of living cells and discovered that practically all mitochondria‐bound Bcl‐xL and tBid are associated with each other, in contrast to undetectable association in the cytosol. Furthermore, we show further applicability of our method to other mitochondrial proteins, as well as to proteins in the endoplasmic reticulum (ER) membrane.
PP4-dependent HDAC3 dephosphorylation discriminates between axonal regeneration and regenerative failure
2018-10-18

The molecular mechanisms discriminating between regenerative failure and success remain elusive. While a regeneration-competent peripheral nerve injury mounts a regenerative gene expression response in bipolar dorsal root ganglia (DRG) sensory neurons, a regeneration-incompetent central spinal cord injury does not. This dichotomic response offers a unique opportunity to investigate the fundamental biological mechanisms underpinning regenerative ability. Following a pharmacological screen with small molecule inhibitors targeting key epigenetic enzymes in DRG neurons we identified HDAC3 signalling as a novel candidate brake to axonal regenerative growth. In vivo, we determined that only a regenerative peripheral but not a central spinal injury induces an increase in calcium, which activates protein phosphatase 4 that in turn dephosphorylates HDAC3 thus impairing its activity and enhancing histone acetylation. Bioinformatics analysis of ex vivo H3K9ac ChIPseq and RNAseq from DRG followed by promoter acetylation and protein expression studies implicated HDAC3 in the regulation of multiple regenerative pathways. Finally, genetic or pharmacological HDAC3 inhibition overcame regenerative failure of sensory axons following spinal cord injury. Together, these data indicate that PP4-dependent HDAC3 dephosphorylation discriminates between axonal regeneration and regenerative failure.
Previous TAVR in patients undergoing percutaneous edge-to-edge mitral valve repair (PMVR) affects improvement of MR
2018-10-19

PMVR in patients who had a TAVR before, is associated with altered MR anatomy before and a reduced improvement of MR after the procedure. Future larger and prospective studies will have to determine, whether a previous TAVR influences long-term clinical outcome of patients undergoing PMVR.