julilili42/papers huggingface dataset:
Is there evidence for unconscious processing of digits?
2019-09-06

It is often argued that humans can discriminate stimuli outside consciousness. In a typical paradigm a stimulus (the ‘prime’) is masked such that participants are hardly aware of it. In a ‘direct task’, participants discriminate the prime and are close to chance, suggesting that they do not perceive the prime consciously. In an ‘indirect’ task, participants discriminate a ‘target’ stimulus following the prime. Here, the prime has congruency effects on reaction times (participants are faster if prime and target belong to the same category). This is seen as evidence for better discrimination in the indirect task and preserved unconscious processing. However, this reasoning is only correct if the congruency effect is converted to an appropriate discrimination performance and then compared to the discrimination in the direct task (Franz & Luxburg, Psychological Science, 2015). Because this is rarely done, the literature on priming effects needs reconsideration. We performed two studies replicating and extending well established effects (cf. the behavioral experiments of Dehaene et al., Nature, 1998): Primes and targets were digits and participants discriminated their numerical size. In experiment 1 (N=18), we found a congruency effect of 11.3 ms (t(17)=4.2, p< 0.001) in the indirect task, replicating the literature. However, the discrimination performance in the indirect task (55.3 %) did not exceed the direct task performance (54.1 %, t(17)=1.1, p=0.3). In experiment 2 (N=20), prime visibility was varied using eight different prime contrasts. We again found congruency effects between 13 and 29 ms (all ps < 0.02), but no better discrimination in the indirect task. These results indicate that --- at least for our stimuli --- there is no better or preserved unconscious processing of the numerical value of digits in cases where conscious discrimination is close to chance.
Comparing Search Strategies of Humans and Machines in Clutter
2019-09-06

While many perceptual tasks become more difficult in the presence of clutter, in general the human visual system has evolved tolerance to cluttered environments. In contrast, current machine learning approaches struggle in the presence of clutter. We compare human observers and CNNs on two target localization tasks with cluttered images created from characters or rendered objects. Each task sample consists of such a cluttered image as well as a separate image of one object which has to be localized. Human observers are asked to identify wether the object lies in the left or right half of the image and accuracy, reaction time and eye movements are recorded. CNNs are trained to segment the object and the position of the center of mass of the segmentation mask is then used to predict the position. Clutter levels are defined by the set-size ranging from 2 to 256 objects per image. We find that for humans processing times increase with the amount of clutter while for machine learning models accuracy drops. This points to a critical difference in human and machine processing: humans search serially whereas current machine learning models typically process a whole image in one pass. Following this line of thought we show that machine learning models with two iterations of processing perform significantly better than the purely feed-forward CNNs dominating in current object recognition applications. This finding suggests that confronted with challenging scenes iterative processing might be just as important for machines as it is for humans.
Human CCR5high effector memory cells perform CNS parenchymal immune surveillance via GZMK-mediated transendothelial diapedesis
2019-09-07

Specific immune-cell populations patrol the CNS in search of pathogens and tumours. Herich et al. identify CD4+ CCR5high GzmK+ effector-memory cells as a brain-surveilling subpopulation capable of crossing the uninflamed blood-brain barrier, and reveal alterations in this population in HIV+ patients with neurological symptoms and in patients with multiple sclerosis.
Mapping the S1 and S1’ subsites of cysteine proteases with new dipeptidyl nitrile inhibitors as trypanocidal agents
2019-09-08

Abstract The cysteine protease cruzipain is considered to be a validated target for therapeutic intervention in the treatment of Chagas disease. A series of 26 new compounds waswere designed, synthesized, and tested against the recombinant cruzain (Cz) to map its S1/S1′ subsites. The same series was evaluated on a panel of four human cysteine proteases (CatB, CatK, CatL, CatS) and Leishmania mexicana CPB, which is a potential target for the treatment of cutaneous leishmaniasis. The synthesized compounds are dipeptidyl nitriles designed based on the most promising combinations of different moieties in P1 (ten), P2 (six), and P3 (four different building blocks). Eight compounds exhibited a K i smaller than 20.0 nM for Cz, whereas three compounds met these criteria for LmCPB. The three inhibitors had an EC 50 value of ca. 4 μM, thus being equipotent to benznidazole according to the anti-trypanosomal effects. Our mapping approach and the respective structure-activity relationships provide insights into the specific ligand-target interactions for therapeutically relevant cysteine proteases. Author Summary Despite many achievements in identifying novel agents for the treatment of tropical and neglected diseases, further research continues to be of fundamental importance. Our research groups have been using the cruzipain cysteine protease in its recombinant form, cruzain (Cz), to identify new trypanocidal agents. Considering the possible interchangeability with other cysteine proteases, the same series of dipeptidyl nitriles was tested in Leishmania mexicana LmCPB. Other potential targets for such inhibitors are human cysteine cathepsins, which are involved in different disease states. Thus, the inhibitors were also tested against cathepsins B, L, K, and S. Our results demonstrate that inhibition of these cysteine proteases can be achieved by appropriate structural modifications of dipeptidyl nitriles. It was also possible to identify trypanocidal agents, equipotent to benznidazole, the current drug of choice used for the treatment of Chagas disease.
Positron Emission Tomography–Guided Treatment in Early-Stage Favorable Hodgkin Lymphoma: Final Results of the International, Randomized Phase III HD16 Trial by the German Hodgkin Study Group
2019-09-09

PURPOSE Combined-modality treatment (CMT) with 2× ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) and small-field radiotherapy is standard of care for patients with early-stage favorable Hodgkin lymphoma (HL). However, the role of radiotherapy has been challenged. Positron emission tomography (PET) after 2× ABVD (PET-2) might help to predict individual outcomes and guide treatment. METHODS Between November 2009 and December 2015, we recruited patients age 18 to 75 years with newly diagnosed, early-stage favorable HL for this international randomized phase III trial. Patients were assigned to standard CMT of 2× ABVD and 20-Gy involved-field radiotherapy or PET-guided treatment, omitting involved-field radiotherapy after negative PET-2 (Deauville score &lt; 3). Primary objectives were to exclude inferiority of 10% or more in 5-year progression-free survival (PFS) of ABVD alone compared with CMT in a per-protocol analysis among PET-2–negative patients (noninferiority margin for hazard ratio, 3.01) and to confirm PET-2 positivity (Deauville score ≥ 3) as a risk factor for PFS among CMT-treated patients. RESULTS We enrolled 1,150 patients. Median follow-up was 45 months. Among 628 PET-2–negative, per-protocol–treated patients, 5-year PFS was 93.4% (95% CI, 90.4% to 96.5%) with CMT and 86.1% (95% CI, 81.4% to 90.9%) with ABVD (difference 7.3% [95% CI, 1.6% to 13.0%]; hazard ratio, 1.78 [95% CI, 1.02 to 3.12]). Five-year overall survival was 98.1% (95% CI, 96.5% to 99.8%) with CMT and 98.4% (95% CI, 96.5% to 100.0%) with ABVD. Among 693 patients who were assigned to CMT, 5-year PFS was 93.2% (95% CI, 90.2% to 96.2%) among PET-2–negative patients and 88.4% (95% CI, 84.2% to 92.6%) in PET-2–positive patients ( P = .047). When using the more common liver cutoff (Deauville score, 4) for PET-2 positivity, the difference was more pronounced (5-year PFS, 93.1% [95% CI, 90.7% to 95.5%] v 80.9% [95% CI, 72.2% to 89.7%]; P = .0011). CONCLUSION In early-stage favorable HL, a positive PET after two cycles ABVD indicates a high risk for treatment failure, particularly when a Deauville score of 4 is used as a cutoff for positivity. In PET-2–negative patients, radiotherapy cannot be omitted from CMT without clinically relevant loss of tumor control.
Long-term adult human brain slice cultures as a model system to study human CNS circuitry and disease
2019-09-09

Most of our knowledge on human CNS circuitry and related disorders originates from model organisms. How well such data translate to the human CNS remains largely to be determined. Human brain slice cultures derived from neurosurgical resections may offer novel avenues to approach this translational gap. We now demonstrate robust preservation of the complex neuronal cytoarchitecture and electrophysiological properties of human pyramidal neurons in long-term brain slice cultures. Further experiments delineate the optimal conditions for efficient viral transduction of cultures, enabling ‘high throughput’ fluorescence-mediated 3D reconstruction of genetically targeted neurons at comparable quality to state-of-the-art biocytin fillings, and demonstrate feasibility of long term live cell imaging of human cells in vitro. This model system has implications toward a broad spectrum of translational studies, regarding the validation of data obtained in non-human model systems, for therapeutic screening and genetic dissection of human CNS circuitry.
Multicountry Distribution and Characterization of Extended-spectrum β-Lactamase–associated Gram-negative Bacteria From Bloodstream Infections in Sub-Saharan Africa
2019-09-09

Abstract Background Antimicrobial resistance (AMR) is a major global health concern, yet, there are noticeable gaps in AMR surveillance data in regions such as sub-Saharan Africa. We aimed to measure the prevalence of extended-spectrum β-lactamase (ESBL) producing Gram-negative bacteria in bloodstream infections from 12 sentinel sites in sub-Saharan Africa. Methods Data were generated during the Typhoid Fever Surveillance in Africa Program (TSAP), in which standardized blood cultures were performed on febrile patients attending 12 health facilities in 9 sub-Saharan African countries between 2010 and 2014. Pathogenic bloodstream isolates were identified at the sites and then subsequently confirmed at a central reference laboratory. Antimicrobial susceptibility testing, detection of ESBL production, and conventional multiplex polymerase chain reaction (PCR) testing for genes encoding for β-lactamase were performed on all pathogens. Results Five hundred and five pathogenic Gram-negative bloodstream isolates were isolated during the study period and available for further characterization. This included 423 Enterobacteriaceae. Phenotypically, 61 (12.1%) isolates exhibited ESBL activity, and genotypically, 47 (9.3%) yielded a PCR amplicon for at least one of the screened ESBL genes. Among specific Gram-negative isolates, 40 (45.5%) of 88 Klebsiella spp., 7 (5.7%) of 122 Escherichia coli, 6 (16.2%) of 37 Acinetobacter spp., and 2 (1.3%) of 159 of nontyphoidal Salmonella (NTS) showed phenotypic ESBL activity. Conclusions Our findings confirm the presence of ESBL production among pathogens causing bloodstream infections in sub-Saharan Africa. With few alternatives for managing ESBL-producing pathogens in the African setting, measures to control the development and proliferation of AMR organisms are urgently needed.
Improved Detection of Benign and Malignant Rib Lesions in the Routine Computed Tomography Workup of Oncological Patients Using Automated Unfolded Rib Image Postprocessing
2019-09-09

Objective The aim of this study was to evaluate the performance of the automated computed tomography (CT) postprocessing software unfolded rib images for improved detection of both benign and malignant rib lesions during routine diagnostic workup of oncological patients. Materials and Methods One thousand eight in-patients and out-patients (63.66 ± 14.25 years; range, 18.67–95.67 years; 405 females and 603 males), undergoing chest CT between July 2018 to January 2019 at our institution, were retrospectively evaluated. Patients underwent chest CT alone or as part of a whole-body CT staging/restaging. The CT protocol consisted of the following: 120 kV; 100 mAs; matrix, 512 × 512; collimation, 0.6 mm; reconstructed section thickness of 3 mm and 1 mm using a soft tissue spatial resolution kernel (I30f) and a sharp kernel (B70f). Both transversal image data sets were used for “conventional” diagnosis including coronal reformates with 3-mm slice thickness. One-millimeter slice thickness image data sets of all patients were additionally directed from the scanner to a computational server where they were automatically postprocessed to 3-dimensional unfolded ribs. The “unfolding” of the rib using the centerline as an axis allows a synchronous display and rotation of all ribs by mouse scrolling. These postprocessed image data sets were evaluated in a separate reading session (approximately 4 weeks later). The readers had no information about the underlying medical history or clinical presentation. They were asked to record the lesion number, site of involvement along the rib (proximal, body, distal), number of the involved ribs, and the character of the lesion in terms of lytic versus sclerotic versus mixed lytic/sclerotic. The standard of reference was 18 F-FDG PET, 68 Ga-DOMITATE PET/CT, bone scan, or imaging follow-up (&gt;6 months). Results From a total of 1008 evaluated patients, 763 (73.02%) were hemato-oncologic patients. A total of 104 rib lesions were found by transversal CT image reading, whereas the unfolded rib image reading detected 305 lesions. Eighty-nine were classified malignant, and 202 were classified benign. Detection of malignant rib lesions proved significant both for less than 1 cm ( P &lt; 0.02) and more than 1 cm in diameter ( P &lt; 0.007). The sensitivity, specificity, positive predictive value, and negative predictive value for detection of malignant rib lesions were 97.7%, 98.5%, 96.6%, and 99% for unfolding ribs, and 76.4%, 100%, 92.7%, and 90.5% for conventional (transversal) image reading, respectively. Detection of sclerotic rib lesions and lesions greater than 1 cm in diameter were significantly better ( P &lt; 0.01) for the unfolding rib algorithm. Conclusions The “unfolded rib” reformates are significantly superior for rib lesion detection compared with conventional transversal CT scan reading and should therefore be used in all patients, particularly those with an oncologic background.
FlashCam: a fully digital camera for the Cherenkov telescope array medium-sized telescopes
2019-09-09

FlashCam is an innovative camera designed for the focal plane instrumentation of Cherenkov telescopes. The concept of the FlashCam trigger and readout system is based on the continuous digitization and digital processing of the photo detector signals on FPGAs, and on a high performance, Ethernet-based front-end readout. Because of the modular design, the electronics that have been developed can serve either photomultiplier tubes or silicon-based photon detectors. In the framework of the CTA (Cherenkov telescope array) project, the FlashCam team has developed a PMT-based camera that is suitable for the medium-sized telescopes. With over 100 Cherenkov telescopes, the CTA observatory will run the most sensitive ground-based telescope systems for TeV gamma-ray astronomy when the two arrays in the Northern and Southern Hemisphere (with three different telescope sizes) will go into operation in the upcoming years.
DNA methylation of sarcosine dehydrogenase (SARDH) loci as a prognosticator for renal cell carcinoma
2019-09-09

DNA methylation plays an important role in the genesis and progression of tumor diseases. To identify new DNA methylation markers possibly associated with the clinical characteristics of renal cell carcinoma (RCC), we investigated loci in the sarcosine dehydrogenase (SARDH) gene. SARDH is involved in the metabolism of the glycine‐derivative sarcosine and is closely linked through a functional control loop. Statistical evaluation of methylation data and clinical characteristics of patients showed that kidney tumors with clinically aggressive features such as a high tumor stage, positive lymph nodes, distant metastases or a previously advanced tumor status exhibited significantly lower methylation of a locus in the SARDH gene. Moreover, SARDH methylation was found to be a significant prognostic factor for recurrence‐free survival in RCC patients showing statistical independence from the clinical prognosticators, grade, stage and state of metastasis. In conclusion, the methylation status of the SARDH‐CGI was identified as an independent prognostic candidate marker for RCC.
Plant community stability results from shifts in species assemblages following whole community transplants across climates
2019-09-09

Climate change will decrease precipitation and increase rainfall variability in eastern Mediterranean regions, with responses of plant communities largely uncertain. Here, we tested short‐term responses of dryland plant communities to contrasting rainfall regimes using reciprocal transplants of soil and seed banks. We exposed three annual plant communities to very different climatic conditions along a steep rainfall gradient. We tested for the role of climate versus community origin on community response and resistance. In parallel, we asked whether origin‐specific climatic adaptations predict compositional shifts across climates. Due to an extreme drought, all plants in the driest climate failed to reach maturity. For the remaining two community origins, the most dry‐adapted species in each community increased in dry climate and the wet‐adapted species increased in wet climate. Dry community origins showed large compositional shifts while maintaining stable plant density, biomass and species richness across climates. Conversely, wet communities showed smaller compositional shifts, but larger variation in biomass and richness. This asynchrony in species abundances in response to rainfall variability could maintain structural community stability. This, in combination with seed dormancy, has the ability to delay extinction in response to climate change. However, increasing occurrence of extreme droughts may, in the long‐term, lead to loss of wet‐adapted species.
ECG changes after percutaneous edge‐to‐edge mitral valve repair
2019-09-09

ABSTRACT Background Mitral regurgitation (MR) has a severe impact on hemodynamics and induces severe structural changes in the left atrium. Atrial remodeling is known to alter excitability and conduction in the atrium facilitating atrial fibrillation and atrial flutter. PMVR is a feasible and highly effective procedure to reduce MR in high‐risk patients, which are likely to suffer from atrial rhythm disturbances. So far, electroanatomical changes after PMVR have not been studied. Hypothesis In the current study, we investigated changes in surface electrocardiograms (ECGs) of patients undergoing PMVR for reduction of MR. Methods We evaluated 104 surface ECGs from patients in sinus rhythm undergoing PMVR. P wave duration, P wave amplitude, PR interval, QRS duration, QRS axis, and QT interval were evaluated before and after PMVR and at follow‐up. Results We found no changes in QRS duration, QRS axis, and QT interval after successful PMVR. However, P wave duration, amplitude, and PR interval were significantly decreased after reduction of MR through PMVR ( P &lt; .05, respectively). Conclusion The data we provide offers insight into changes in atrial conduction after reduction of MR using PMVR in patients with sinus rhythm.
The Typhoid Fever Surveillance in Africa Program: Geospatial Sampling Frames for Household-based Studies: Lessons Learned From a Multicountry Surveillance Network in Senegal, South Africa, and Sudan
2019-09-09

Abstract Background Robust household sampling, commonly applied for population-based investigations, requires sampling frames or household lists to minimize selection bias. We have applied Google Earth Pro satellite imagery to constitute structure-based sampling frames at sites in Pikine, Senegal; Pietermaritzburg, South Africa; and Wad-Medani, Sudan. Here we present our experiences in using this approach and findings from assessing its applicability by determining positional accuracy. Methods Printouts of satellite imagery combined with Global Positioning System receivers were used to locate and to verify the locations of sample structures (simple random selection; weighted-stratified sampling). Positional accuracy was assessed by study site and administrative subareas by calculating normalized distances (meters) between coordinates taken from the sampling frame and on the ground using receivers. A higher accuracy in conjunction with smaller distances was assumed. Kruskal-Wallis and Dunn multiple pairwise comparisons were performed to evaluate positional accuracy by setting and by individual surveyor in Pietermaritzburg. Results The median normalized distances and interquartile ranges were 0.05 and 0.03–0.08 in Pikine, 0.09 and 0.05–0.19 in Pietermaritzburg, and 0.05 and 0.00–0.10 in Wad-Medani, respectively. Root mean square errors were 0.08 in Pikine, 0.42 in Pietermaritzburg, and 0.17 in Wad-Medani. Kruskal-Wallis and Dunn comparisons indicated significant differences by low- and high-density setting and interviewers who performed the presented approach with high accuracy compared to interviewers with poor accuracy. Conclusions The geospatial approach presented minimizes systematic errors and increases robustness and representativeness of a sample. However, the findings imply that this approach may not be applicable at all sites and settings; its success also depends on skills of surveyors working with aerial data. Methodological modifications are required, especially for resource-challenged sites that may be affected by constraints in data availability and area size.