julilili42/papers huggingface dataset:
Genetic evolution of <i>in situ</i> follicular neoplasia to aggressive B-cell lymphoma of germinal center subtype
2020-08-27

In situ follicular neoplasia (ISFN) is the earliest morphologically identifiable precursor of follicular lymphoma (FL). Although it is genetically less complex than FL and has low risk for progression, ISFN already harbors secondary genetic alterations, in addition to the defining t(14;18)(q32;q21) translocation. FL, in turn, frequently progresses to diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBL). By BCL2 staining of available reactive lymphoid tissue obtained at any time point in patients with aggressive B-cell lymphoma (BCL), we identified ten paired cases of ISFN and DLBCL/HGBL, including six de novo tumors and four tumors transformed from FL as an intermediate step, and investigated their clonal evolution using microdissection and next-generation sequencing. A clonal relationship between ISFN and aggressive BCL was established by immunoglobulin and/or BCL2 rearrangements and/or the demonstration of shared somatic mutations for all ten cases. Targeted sequencing revealed CREBBP, KMT2D, EZH2, TNFRSF14 and BCL2 as the genes most frequently mutated already in ISFN. Based on the distribution of private and shared mutations, two patterns of clonal evolution were evident. In most cases, the aggressive lymphoma, ISFN and, when present, FL revealed divergent evolution from a common progenitor, whereas linear evolution with sequential accumulation of mutations was less frequent. In conclusion, we demonstrate for the first time that t(14;18)+ aggressive BCL can arise from ISFN without clinically evident FL as an intermediate step and that during this progression, branched evolution is common.
On Counterfactual Explanations under Predictive Multiplicity.
2020-08-27

Counterfactual explanations are usually obtained by identifying the smallest change made to an input to change a prediction made by a fixed model (hereafter called sparse methods). Recent work, however, has revitalized an old insight: there often does not exist one superior solution to a prediction problem with respect to commonly used measures of interest (e.g. error rate). In fact, often multiple different classifiers give almost equal solutions. This phenomenon is known as predictive multiplicity (Breiman, 2001; Marx et al., 2019). In this work, we derive a general upper bound for the costs of counterfactual explanations under predictive multiplicity. Most notably, it depends on a discrepancy notion between two classifiers, which describes how differently they treat negatively predicted individuals. We then compare sparse and data support approaches empirically on real-world data. The results show that data support methods are more robust to multiplicity of different models. At the same time, we show that those methods have provably higher cost of generating counterfactual explanations under one fixed model. In summary, our theoretical and empiricaln results challenge the commonly held view that counterfactual recommendations should be sparse in general.
The fluorescence of resin-based composites: An analysis after ten years of aging
2020-08-27

The long-term preservation of fluorescence qualities of resin-based composite (RBC) restorations is an absolute condition for the implementation of the fluorescence-aided identification technique (FIT) in dentistry and forensic medicine. Therefore, this study assessed the fluorescence of 244 color shades of 16 commercially available RBC brands with a monochromator-based multimode microplate reader. The specimens were stored in the dark at room temperature and reassessed ten years after the initial investigation. The mean intensity of the fluorescence maxima decreased from (31,030±936) RFU to (22,027±632) RFU. Linear regression resulted in r2=0.972 and a slope=0.701±0.005. The fluorescence intensity of the tested RBCs dropped to about 70% of the initial intensity independent of the brand, color shade and initial fluorescence intensity. On the basis of this in vitro 10-year data set, we assume that in vivo RBC fluorescence is also suitable for the detection and differentiation of clinically aged RBC restorations by FIT.
Persistent common arterial trunk with hexaleaflet truncal valve and intact ventricular septum
2020-08-27

Abstract We report a case of a 3-week-old infant who presented a heart murmur and low oxygen saturation. An echocardiography was performed and presented a common arterial trunk type B4 with an interrupted aortic arch and intact ventricular septum. We describe the surgical management and short-term follow-up.
A Dataset of EEG and EOG recordings from an Auditory EOG-based Communication System for Patients in Locked-In State
2020-08-27

&lt;p&gt;The dataset presented here contains recordings of electroencephalogram (EEG) and electrooculogram (EOG) from four advanced locked-in state (LIS) patients. These patients could not use commercial eye-trackers anymore. However, they could still move their eyes and used the remnant oculomotor activity to select letters to form words and sentences using a novel auditory communication system, relying on the auditory channel, due to the often-compromised vision of these patients. The patients performed a succession of different sessions, namely, Training, Feedback, Copy spelling, and Free spelling, with the purpose of developing and dominate an oculomotor strategy to successfully control the spelling system. Data were recorded from 4 patients during a variable range of visits (from 2 to 10), each visit comprised of 3.22&plusmn;1.21 days and consisted of 5.57&plusmn;2.61 sessions recorded per day. Training and Feedback sessions consist of 20 trials (10 questions with &ldquo;yes&rdquo; answer and 10 questions with &ldquo;no&rdquo; answer) each&rdquo;. In contrast, Copy and Free spelling sessions consisted of a variable number of trials depending on the length of the words, phrases, and sentences formed by the patient. Each trial consisted of 4 different segments: baseline, auditory stimuli presentation, response, and feedback to the patient. The uniqueness of this data (i.e., the patients and the progression) and its nature (mid and long-term recordings, with EEG and EOG electrodes), make it a quite specific, but a valuable opportunity for defining and improving augmentative and alternative communication technologies and brain-computer interfaces, and contribute to improving clinical and therapeutic practices related to ALS patients.&lt;/p&gt;
Uncertainty Tolerance &amp; Cognitive Control
2020-08-27

Cognitive control refers to the ability to make correct decisions concurrent to distracting information, and to adapt to conflicting stimulus configurations, eventually promoting goal-directed behavior. Previous research has linked individual differences in cognitive control to psychopathological conditions such as anxiety. However, a link with uncertainty tolerance (UT) has not been tested so far, although both constructs describe cognitive and behavioral performance in ambiguous situations, thus they share some similarities. We probed cognitive control in web-based experimentation (jsPsych) with a simple flanker task (N = 111) and a version without confounds in episodic memory (N = 116). Both experiments revealed two well-established behavioral indices: congruency effects (CEs) and congruency-sequence effects (CSEs). Only small-to-zero correlations emerged between CEs, UT, and need for cognitive closure (NCC), a personality trait inversely related to UT. A subtle correlation (r = .18) was noted in Experiment 2 between NCC and CSE. Throughout, Bayesian analyses provided anecdotal-to-moderate evidence for the null-hypotheses.
Carbenaporphyrins: A Missing Ligand in N-Heterocyclic Carbene Chemistry
2020-08-27

The successful synthesis of a carbenaporphyrin ligand based on carbazole and triazolylidene (CTP) is reported. Instead of a macrocyclic aromatic or antiaromatic character, the aromaticity of each heterocyclic moiety is preserved, which results in optical properties different from porphyrins, e.g. fluorescence. In Li + and Sc 3+ complexes the ligand reveals striking geometric similarity to porphyrins, but is stronger electron donating.
Retrospective accuracy analysis of MRI based lesion size measurement in neuroblastic tumors: which sequence should we choose?
2020-08-27

<title>Abstract</title> <bold>Background: </bold>MR imaging of neuroblastic tumors is widely used for assessing the effect of chemotherapy on tumor size. However, there are some concerns that MRI might falsely estimate lesion diameters due to calcification and fibrosis.<bold> </bold>Therefore, the aim of our study was to compare neuroblastic tumor size based on MRI measurements to histopathology measurements of the resected specimens as standard of reference.<bold>Methods: </bold>Inclusion criteria were diagnosis of a neuroblastic tumor, MR imaging within 100 days to surgery and gross total resection without fragmentation of the tumor between 2008-2019. Lesion diameters were measured by two radiologists according to RECIST 1.1 in axial plane in T2w turbo spin echo (TSE), diffusion-weighted imaging (DWI), and in T1w pre- and postcontrast sequences. Furthermore, the largest lesion size in three-dimensions was noted. The largest diameter of histopathology measurements of each specimen was used for comparison with MRI.<bold>Results: </bold>Thirty-seven patients (mean age: 5±4 years) with 38 lesions (neuroblastoma: n=17; ganglioneuroblastoma: n=11; ganglioneuroma: n=10) were included in this retrospective study. There was excellent intra-class correlation coefficient between both readers for all sequences (&gt;0.9) Tumor dimensions of reader 1 based on axial MRI measurements were significantly smaller with the following median differences (cm): T1w precontrast -1.4 (interquartile range (IQR): 1.8 ), T1w postcontrast -1.0 (IQR: 1.9), T2w TSE: -1.0 (IQR: 1.6), and DWI -1.3 (IQR: 2.2) (p&lt;0.001 for all sequences). However, the evaluation revealed no significant differences between the three-dimensional measurements and histopathology measurements of the resected specimens regardless of the applied MRI sequence.<bold>Conclusions: </bold>Axial MRI based lesion size measurements are significantly smaller than histopathological measurements. However, there was no significant difference between three-dimensional measurements and histopathology measurements of the resected specimens. T2w TSE and T1w postcontrast images provided the lowest deviation and might consequently be preferred for measurements.
Antimicrobial resistance preparedness in sub-Saharan African countries
2020-08-28

Abstract Background Antimicrobial resistance (AMR) is of growing concern globally and AMR status in sub-Saharan Africa (SSA) is undefined due to a lack of real-time data recording, surveillance and regulation. World Health Organization (WHO) Joint External Evaluation (JEE) reports are voluntary, collaborative processes to assess country capacities and preparedness to prevent, detect and rapidly respond to public health risks, including AMR. The data from SSA JEE reports were analysed to gain an overview of how SSA is working towards AMR preparedness and where strengths and weaknesses lie. Methods SSA country JEE AMR preparedness scores were analysed. A cumulative mean of all the SSA country AMR preparedness scores was calculated and compared to the overall mean SSA JEE score. AMR preparedness indicators were analysed, and data were weighted by region. Findings The mean SSA AMR preparedness score was 53% less than the overall mean SSA JEE score. East Africa had the highest percentage of countries reporting having AMR National Action Plans in place, as well as human and animal pathogen AMR surveillance programmes. Southern Africa reported the highest percentage of countries with training programmes and antimicrobial stewardship. Conclusions The low mean AMR preparedness score compared to overall JEE score, along with the majority of countries lacking implemented National Action Plans, suggests that until now AMR has not been a priority for most SSA countries. By identifying regional and One Health strengths, AMR preparedness can be fortified across SSA with a multisectoral approach.
Loss‐of‐Function Variants in HOPS Complex Genes VPS16 and VPS41 Cause Early Onset Dystonia Associated with Lysosomal Abnormalities
2020-08-28

Objectives The majority of people with suspected genetic dystonia remain undiagnosed after maximal investigation, implying that a number of causative genes have not yet been recognized. We aimed to investigate this paucity of diagnoses. Methods We undertook weighted burden analysis of whole‐exome sequencing (WES) data from 138 individuals with unresolved generalized dystonia of suspected genetic etiology, followed by additional case‐finding from international databases, first for the gene implicated by the burden analysis ( VPS16 ), and then for other functionally related genes. Electron microscopy was performed on patient‐derived cells. Results Analysis revealed a significant burden for VPS16 (Fisher's exact test p value, 6.9 × 10 9 ). VPS16 encodes a subunit of the homotypic fusion and vacuole protein sorting (HOPS) complex, which plays a key role in autophagosome‐lysosome fusion. A total of 18 individuals harboring heterozygous loss‐of‐function VPS16 variants, and one with a microdeletion, were identified. These individuals experienced early onset progressive dystonia with predominant cervical, bulbar, orofacial, and upper limb involvement. Some patients had a more complex phenotype with additional neuropsychiatric and/or developmental comorbidities. We also identified biallelic loss‐of‐function variants in VPS41 , another HOPS‐complex encoding gene, in an individual with infantile‐onset generalized dystonia. Electron microscopy of patient‐derived lymphocytes and fibroblasts from both patients with VPS16 and VPS41 showed vacuolar abnormalities suggestive of impaired lysosomal function. Interpretation Our study strongly supports a role for HOPS complex dysfunction in the pathogenesis of dystonia, although variants in different subunits display different phenotypic and inheritance characteristics. ANN NEUROL 2020;88:867–877
Antimicrobial Activities of Different Fractions from Mucus of the Garden Snail Cornu aspersum
2020-08-28

Natural products have long played a major role in medicine and science. The garden snail Cornu aspersum is a rich source of biologically active natural substances that might be an important source for new drugs to treat human disease. Based on our previous studies, nine fractions containing compounds with Mw &lt;3 kDa; &lt;10 kDa; &lt;20 kDa; &gt;20 kDa; &gt;30 kDa&gt;50 kDa and between 3 and 5 kDa; 5 and 10 kDa; and 10 and 30 kDa were purified from the mucus of C. aspersum and analyzed by tandem mass spectrometry (MALDI-TOF/TOF). Seventeen novel peptides with potential antibacterial activity were identified by de novo MS/MS sequencing using tandem mass spectrometry. The different fractions were tested for antibacterial activity against Gram─ (Pseudomonas aureofaciens and Escherichia coli) and Gram+ (Brevibacillus laterosporus) bacterial strains as well the anaerobic bacterium Clostridium perfringens. These results revealed that the peptide fractions exhibit a predominant antibacterial activity against B. laterosporus; the fraction with Mw 10–30 kDa against E. coli; another peptide fraction &lt;20 kDa against P. aureofaciens; and the protein fraction &gt;20 kDa against the bacterial strain C. perfringens. The discovery of new antimicrobial peptides (AMPs) from natural sources is of great importance for public health due to the AMPs’ effective antimicrobial activities and low resistance rates.
Longitudinal Serum Neurofilament Levels of Multiple Sclerosis Patients Before and After Treatment with First-Line Immunomodulatory Therapies
2020-08-28

Serum neurofilament light chain (NfL) has been shown to correlate with neuroaxonal damage in multiple sclerosis (MS) and various other neurological diseases. While serum NfL is now regularly reported in clinical approval studies, there is a lack of longitudinal data from patients treated with established basic immunotherapies outside of study conditions. In total, 34 patients with early relapsing-remitting MS (RRMS) were included. The follow-up period was 24 months with regular follow-up visits after 3, 6, 9, 12 and 18 months. Therapy with glatiramer acetate was initiated in 20 patients and with interferon-beta in 12 patients. The disease course was monitored by the events of relapses, Expanded Disability Status Scale (EDSS) score and MRI parameters. Overall, serum NfL levels were higher at time points with a current relapse event than at time points without relapse (12.8 pg/mL vs. 9.7 pg/mL, p = 0.011). At follow-up, relapse-free patients showed significantly reduced serum NfL levels starting from 9 months compared to baseline (p &lt; 0.05) and reduced levels after 12 months compared to baseline (p = 0.013) in patients without EDSS progression for 12 months. In this explorative observational study, our data suggest that the longitudinal measurement of serum NfL may be useful in addition to MRI to monitor disease activity and therapy response.
Mastocytosis
2020-08-28

Abstract Objectives The 2019 Workshop of the Society for Hematopathology/European Association for Haematopathology received and reviewed cases covering the spectrum of mastocytosis and related diseases, including morphologic mimics, focusing on recent updates and relevant findings for pathologists. Methods The workshop panel reviewed 99 cases of cutaneous and systemic mastocytosis (SM) and SM and associated hematologic neoplasms (SM-AHN). Results Despite a common theme of KIT mutation (particularly D816V), mastocytosis is a heterogeneous neoplasm with a wide variety of presentations. This spectrum, including rare subtypes and extramedullary organ involvement, is discussed and illustrated by representative cases. Conclusions In the age of targeted treatment aimed at KIT, the accurate diagnosis and classification of mastocytosis has major implications for therapy and further interventions. Understanding the clinical, pathologic, and genetic findings of mastocytosis is crucial for selecting the proper tests to perform and subsequent arrival at a correct diagnosis in this rare disease.
Quo Vadis, Molecular Imaging?
2020-08-28

The important insights yielded by molecular imaging (MI) into relevant biologic signatures at an organ-specific and systemic level are not achievable with conventional imaging methods and thus provide an essential link between preclinical and clinical research. New diagnostic probes and imaging methods revealing comprehensive functional and molecular information are being provided by MI research, several of which have found their way into clinical application. However, there are also reservations about the impact of MI and its added value over conventional, often less expensive, diagnostic imaging methods. This perspective discusses seminal research directions for the MI field that have the potential to result in added value to the patient. Emphasis is placed on MI without probes, MI based on radiotracers and small molecules, MI nano- and microsystems, and MI in context with comprehensive diagnostics. Furthermore, besides technical innovations and probes, emerging clinical indications are highlighted.
A Peculiar Cyclotron Line near 16 keV Detected in the 2015 Outburst of 4U 0115+63?
2020-08-28

Abstract In 2015 October, the Be/X-ray binary 4U 0115+63 underwent a type II outburst, reaching an X-ray luminosity of ∼10 38 erg s −1 . During the outburst, Nuclear Spectroscopic Telescope Array (NuSTAR) performed two Target of Opportunity observations. Using the broadband spectra from NuSTAR (3–79 keV), we have detected multiple cyclotron lines of the source, i.e., ∼12, 16, 22, and 33/35 keV. Obviously, the 16 keV line is not a harmonic component of the 12 keV line. As described by the phase-dependent equivalent widths of these cyclotron lines, the 16 keV and 12 keV lines are two different fundamental lines. In our work, we apply the two-poles cyclotron line model to the observation, i.e., the two line sets are formed at the same altitude (∼0.2 km over the NS surface) of different magnetic poles, with ∼1.1 × 10 12 and 1.4 × 10 12 G in two poles, respectively.
Overview: Standards for Modeling in Systems Medicine
2020-08-28

Computational analyses of digital information constitute the foundation for modern scientific research. The analysis of computer models can, for instance, guide experimentalists or predict biological functions such as novel drug targets or recovery from external stress. In many cases, such analyses require several bioinformatics tools to interoperate in complex workflows. To this end, the scientific community has been developing clear standards for automatic interpretation and use of computer models within complex computer analysis pipelines for systems biomedicine. The standard development process follows two fundamental design decisions: (i) to organize the information in a modular fashion and (ii) to strictly separate models from methods for their analysis. Following these principles, a complex ecosystem of modeling guidelines, annotation schemes, and representation formats has evolved, for which enthusiastic community members create and maintain rich documentation and necessary software infrastructure. The resulting standards cover model development, storage, the exchange between different analysis programs, the display, automated validity and plausibility checks, publication and review, and many other aspects of computational modeling and simulation. The umbrella organization COMBINE coordinates the evolution of and communication between new and existing standards. In this chapter, we introduce the reader to commonly used data formats, guidelines, and ontologies for the storage and exchange of computational models in systems medicine. We focus on models of biological systems, including their structures, annotation, visualization, and interpretation. Additional chapters in this book offer more detailed information on selected data formats. For the construction of models or the integration of data, further literature needs to be consulted.
Effective Viscous Damping Enables Morphological Computation in Legged Locomotion
2020-08-28

Muscle models and animal observations suggest that physical damping is beneficial for stabilization. Still, only a few implementations of mechanical damping exist in compliant robotic legged locomotion. It remains unclear how physical damping can be exploited for locomotion tasks, while its advantages as sensor-free, adaptive force- and negative work-producing actuators are promising. In a simplified numerical leg model, we studied the energy dissipation from viscous and Coulomb damping during vertical drops with ground-level perturbations. A parallel spring-damper is engaged between touch-down and mid-stance, and its damper auto-disengages during mid-stance and takeoff. Our simulations indicate that an adjustable and viscous damper is desired. In hardware we explored effective viscous damping and adjustability and quantified the dissipated energy. We tested two mechanical, leg-mounted damping mechanisms; a commercial hydraulic damper, and a custom-made pneumatic damper. The pneumatic damper exploits a rolling diaphragm with an adjustable orifice, minimizing Coulomb damping effects while permitting adjustable resistance. Experimental results show that the leg-mounted, hydraulic damper exhibits the most effective viscous damping. Adjusting the orifice setting did not result in substantial changes of dissipated energy per drop, unlike adjusting damping parameters in the numerical model. Consequently, we also emphasize the importance of characterizing physical dampers during real legged impacts to evaluate their effectiveness for compliant legged locomotion.