julilili42/papers huggingface dataset:
Efficient Ocular Delivery of VCP siRNA via Reverse Magnetofection in RHO P23H Rodent Retina Explants
2021-02-06

The use of synthetic RNA for research purposes as well as RNA-based therapy and vaccination has gained increasing importance. Given the anatomical seclusion of the eye, small interfering RNA (siRNA)-induced gene silencing bears great potential for targeted reduction of pathological gene expression that may allow rational treatment of chronic eye diseases in the future. However, there is yet an unmet need for techniques providing safe and efficient siRNA delivery to the retina. We used magnetic nanoparticles (MNPs) and magnetic force (Reverse Magnetofection) to deliver siRNA/MNP complexes into retinal explant tissue, targeting valosin-containing protein (VCP) previously established as a potential therapeutic target for autosomal dominant retinitis pigmentosa (adRP). Safe and efficient delivery of VCP siRNA was achieved into all retinal cell layers of retinal explants from the RHO P23H rat, a rodent model for adRP. No toxicity or microglial activation was observed. VCP silencing led to a significant decrease of retinal degeneration. Reverse Magnetofection thus offers an effective method to deliver siRNA into retinal tissue. Used in combination with retinal organotypic explants, it can provide an efficient and reliable preclinical test platform of RNA-based therapy approaches for ocular diseases.
Three‐dimensional histology vs. serial section histology in the treatment of primary basal cell carcinoma: a randomized, prospective, blinded study of 569 tumours
2021-02-06

Abstract Background For basal cell carcinoma (BCC), only few controlled data have been published so far, which directly compare micrographically controlled surgery with conventional serial section histology. In addition to Mohs surgery, which uses cryostat sections, also three‐dimensional histology (3D‐histology), based on paraffin sections, is available to ensure complete control of the margins and basic sections. Objectives To investigate the rate of local recurrence (LR) as well as the number of required re‐excisions for basal cell carcinomas with serial section histology vs. 3D‐histology. Methods We compared serial sections histology with 3D‐histology in a prospective, randomized, controlled blinded trial and analysed 569 BCC of all subtypes up to 30 mm diameter, 287 BCC in the 3D group and 282 BCC in the serial section group. Excisions were performed with adapted primary resection margin according to location and size of the tumour. Surgeons were blinded at the time of surgery as they did not know which histological method will be used. Both methods used paraffin sections. Results Both groups did not differ regarding patients age, tumour location, tumour diameter, tumour subtypes or primary resection margins. In the serial section group, re‐excisions were required in 21%; 24 tumours (8.4%) recurred after a median of 2.2 years. In the 3D‐histology group, re‐excisions were required in 39%; 10 tumours recurred (3.5%) after a median of 2.8 years. The recurrence rates differed significantly between both groups. Mean follow‐up was 4.5 years. Conclusions 3D‐histology is a useful technique to detect tumour outgrowths at the excision margins, but required a high rate of re‐excisions. 3D‐histology was associated with a significantly lower LR rate than serial section histology.
Early response by MR imaging and ultrasound as predictor of pathologic complete response to 12‐week neoadjuvant therapy for different early breast cancer subtypes: Combined analysis from the WSG ADAPT subtrials
2021-02-06

Abstract We evaluated the role of early response after 3 weeks of neoadjuvant treatment (NAT) assessed by ultrasound (US), magnetic resonance imaging (MRI) and Ki‐67 dynamics for prediction of pathologic complete response (pCR) in different early breast cancer subtypes. Patients with HR+/HER2+, HR−/HER2− and HR−/HER2+ tumors enrolled into three neoadjuvant WSG ADAPT subtrials underwent US, MRI and Ki‐67 assessment at diagnosis and after 3 weeks of NAT. Early response was defined as complete or partial response (US, MRI) and ≥30% proliferation decrease or &lt;500 invasive tumor cells (Ki‐67). Predictive values and area under the receiver operating characteristic (AUC) curves for prediction of pCR (ypT0/is ypN0) after 12‐week NAT were calculated. Two hundred twenty‐six had MRI and 401 US; 107 underwent both MRI and US. All three methods yielded a similar AUC in HR+/HER2+ (0.66‐0.67) and HR−/HER2− tumors (0.53‐0.63), while MRI and Ki‐67 performed better than US in HR−/HER2+ tumors (0.83 and 0.79 vs 0.56). Adding MRI+/‐Ki‐67 increased AUC of US in HR−/HER2+ tumors to 0.64 to 0.75. MRI and Ki‐67 demonstrated highest sensitivity in HR−/HER2− (0.8‐1) and HR−/HER2+ tumors (1, both). Negative predictive value was similar for all methods in HR+/HER2+ (0.71‐0.74) and HR−/HER2− tumors (0.85‐1), while it was higher for MRI and Ki‐67 compared to US in HR−/HER2+ subtype (1 vs 0.5). Early response assessed by US, MRI and Ki‐67 is a strong predictor for pCR after 12‐week NAT. Strength of pCR prediction varies according to tumor subtype. Adding MRI+/‐Ki‐67 to US did not improve pCR prediction in majority of our patients.
Comparative Analysis of TMPA and IMERG Precipitation Datasets in the Arid Environment of El-Qaa Plain, Sinai
2021-02-07

The replenishment of aquifers depends mainly on precipitation rates, which is of vital importance for determining water budgets in arid and semi-arid regions. El-Qaa Plain in the Sinai Peninsula is a region that experiences constant population growth. This study compares the performance of two sets of satellite-based data of precipitation and in situ rainfall measurements. The dates selected refer to rainfall events between 2015 and 2018. For this purpose, 0.1° and 0.25° spatial resolution TMPA (Tropical Rainfall Measurement Mission Multi-satellite Precipitation Analysis) and IMERG (Integrated Multi-satellite Retrievals for Global Precipitation Measurement) data were retrieved and analyzed, employing appropriate statistical metrics. The best-performing data set was determined as the data source capable to most accurately bridge gaps in the limited rain gauge records, embracing both frequent light-intensity rain events and more rare heavy-intensity events. With light-intensity events, the corresponding satellite-based data sets differ the least and correlate more, while the greatest differences and weakest correlations are noted for the heavy-intensity events. The satellite-based records best match those of the rain gauges during light-intensity events, when compared to the heaviest ones. IMERG data exhibit a superior performance than TMPA in all rainfall intensities.
Petrogenesis and tectonic setting of the early-middle triassic subduction-related granite in the eastern segment of East Kunlun: evidences from petrology, geochemistry, and zircon U-Pb-Hf isotopes
2021-02-07

The subduction process of the Paleo-Tethyan Ocean is still under controversy. We report zircon U-Pb ages and geochemistry (major and trace elements, and Hf isotopic compositions) for the Xiangjiananshan granitic plutons in the eastern segment of the East Kunlun Orogenic Belt, northern Tibetan Plateau, to constrain the subduction-related granitoids in its petrogenesis and to reconstruct the subduction prosess of the Buqingshan-A'nyemaqing Ocean. Zircon U-Pb dating yields coeval ages of 246.6 ± 4.1 Ma for granodiorite and 246.4 ± 3.9 Ma for biotite monzogranite of the Xiangjiananshan granitoid pluton. The granitoids include granodiorites, biotite monzogranites, and pseudo-porphyritic monzogranites. The granitoids have high contents of SiO2 (66.60–73.19 wt.%) and Al2O3 (13.28–16.38 wt.%), consistent with the high-K calc-alkaline series. The A/CNK ratios range from 0.98 to 1.02, indicating that the granodiorite is metaluminous and weakly peraluminous. The mafic microgranular enclaves (MMEs) in granodiorite and biotite monzogranite have a restricted SiO2 range (57.24–60.03 wt.%), and have higher Fe2O3T, and MgO contents than the host granitoids, as well as higher total rare earth element (REE) concentrations. All samples are depleted in high field strength elements (HFSEs; e.g., Nb, Ta, Ti and P) and heavy rare earth elements (HREEs), and are enriched in large ion lithophile elements (LILEs; e.g., Rb, Nd and La) and light rare earth elements (LREEs). Zircons from the pseudoporphyritic monzogranite yield two-stage model ages of 1137.32 to 1588.12 Ma, together with εHf(t) values from −5.01 to +2.11. These results indicate that the parental magma of pseudoporphyritic monzogranite was generated by partial melting of Paleoproterozoic to Mesoproterozoic rocks of the lower crust with contamination of ancient crustal material. Field and petrological observations, together with elemental and Hf isotopic data, indicate that the Xiangjiananshan granitic plutons was formed by magma mixing of mafic and felsic magmas. The felsic magma was derived from partial melting of the lower crust, while the mafic magma was derived from partial melting of an enriched lithospheric mantle metasomatized by slab-derived fluid due to the subduction of the Buqingshan-A'nyemaqing Ocean. Therefore, we propose that the northward subduction of the Buqingshan-A'nyemaqing ocean north to the Bayan Hara block under East Kunlun initiated in the Middle Permian (ca. 270 Ma), yielding calcium metaluminous arc magmatic rocks with I-type granite characteristics at East Kunlun, including the XG pluton in this study. Subsequently, the Buqingshan-A'nyemaqing ocean closed and resulted in collision of the Bayan Hara and East Kunlun blocks from 240 to 230 Ma.
Mobbing responses of great tits (Parus major) do not depend on the number of heterospecific callers
2021-02-07

Abstract Numerical competence—the ability to estimate and process the number of objects and events—is important during antipredator strategies because it influences individual's survival chances. Animals can benefit from numerical competence during mobbing—when a prey moves toward and vocalizes at or harasses a predator. Mobbing responses of some species are related to the number of conspecific callers, and responses are stronger during playbacks simulating multiple callers. Here, we tested heterospecific individual vocal recognition (IVR) in combination with numerical competence in great tits ( Parus major ). Since previous work showed that great tits respond to mobbing calls of chaffinches ( Fringilla coelebs ), we predict that great tits showed a stronger response when two or four different individual chaffinches were played back versus only one individual by keeping the duty cycle (number of total calls/min) identical. Individuals were exposed to playbacks simulating calling by one, two or four heterospecific callers, or singing by one caller (control song). Great tits approached the speaker closer and produced more calls during the mobbing calls treatments than during the control treatment (song). However, in contrast to our prediction, great tits responded similarly to mobbing calls from several heterospecific callers as they did toward mobbing calls from one heterospecific caller. Maybe the great tits still are capable of determining the identity of the callers, but what might matter most for them in this very specific situation might be the mobbing intensity. We assume that the duty cycle itself has the stronger impact on the response.
Water risks to hydropower projects in the face of climate change
2021-02-07

This repository hosts the main outputs from an analysis using the WWF Water Risk Filter to demonstrate how one such tool can be used to screen for a variety of risks at a global scale, including risks to riverine ecosystems from both climate change and hydropower as well as risks to hydropower projects — and operators, owners, and investors — from climate change and potential regulatory or reputational risk arising from negative impacts to ecosystems. The study is under review in the special issue of the journal Water: "Water Management to Protect Aquatic Ecosystems Function and Health in the Face of Climate Change". This product incorporates data from the GRanD v1.3 database which is © Global Water System Project (2011), and from the FHReD database beta version, both datasets available at globaldamwatch.org. The source code used in this study is available at https://github.com/rafaelatwwf/hydropowerClimateChange.
Water risks to hydropower projects in the face of climate change
2021-02-07

This repository hosts the main outputs from an analysis using the WWF Water Risk Filter to demonstrate how one such tool can be used to screen for a variety of risks at a global scale, including risks to riverine ecosystems from both climate change and hydropower as well as risks to hydropower projects — and operators, owners, and investors — from climate change and potential regulatory or reputational risk arising from negative impacts to ecosystems. The study Using the WWF Water Risk Filter to Screen Existing and Projected Hydropower Projects for Climate and Biodiversity Risks (DOI 10.3390/w14050721) was published in the special issue of the MDPI journal Water: "Hydro-Meteorological Hazards under Climate Change". This product incorporates data from the GRanD v1.3 database which is © Global Water System Project (2011), and from the FHReD database beta version, both datasets available at globaldamwatch.org . The source code used in this study is available at https://github.com/rafaexx/hydropowerClimateChange See the interactive maps using this data at https://rcamargo.shinyapps.io/HydropowerClimateChange
Changing personality traits with the help of a digital personality change intervention
2021-02-08

Significance Personality traits have consequences and are malleable throughout the lifespan. However, it is unclear if and how personality traits can be changed in desired directions. A 3-mo digital personality change intervention was deployed, and a large-scale randomized controlled trial ( n = 1,523) was conducted to examine the effects of intended personality change in a nonclinical sample. The intervention group showed greater changes than the control group, and changes aligned with intended goals for change. Observers also perceived personality changes, but reported changes were less pronounced. Moreover, self- and observer-reported changes persisted until 3 mo after the end of the intervention. These findings provide the strongest evidence to date that normal personality traits can be changed through intervention in nonclinical samples.
Behavioral Changes among Street Level Drug Trafficking Organizations and the Fluctuation in Drug Prices Before and During the Covid-19 Pandemic
2021-02-08

This article focused on behavioral changes in street-level drug trafficking organizations and drug price fluctuations at the retail level during the COVID-19 in Germany, specifically in North Rhine-Westphalia. This study's primary purpose was to understand how the pandemic affected low-level drug markets and whether precautions taken to prevent the spread of disease caused any changes in their operations. Moreover, drug prices were compared before and during the Corona-19 pandemic. This study used a narrative analysis. Thirteen participants, some of whom used multiple drugs and all of whom are regular users, were interviewed from March 2020 to September 2020. Study results showed no significant change either in open or closed markets except for curfew times. Moreover, no shortages existed in the drug supply chain. Nevertheless, there were slight changes in drug distribution methods. Furthermore, contrary to the assumptions, the demand for using the Internet drug market did not increase during the pandemic.
Lattice gas study of thin-film growth scenarios and transitions between them: Role of substrate
2021-02-08

Thin-film growth is investigated in two types of lattice gas models where substrate and film particles are different, expressed by unequal interaction energy parameters. The first is of solid-on-solid type, whereas the second additionally incorporates desorption, diffusion in the gas phase above the film and readsorption at the film (appropriate for growth in colloidal systems). In both models, the difference between particle-substrate and particle-particle interactions plays a central role for the evolution of the film morphology at intermediate times. The models exhibit a dynamic layering transition which occurs at generally lower substrate attraction strengths than the equilibrium layering transition. A second, flattening transition is found where initial island growth transforms to layer-by-layer growth at intermediate deposition times. Combined with the known roughening behavior in such models for very large deposition times, we present four global growth scenarios, charting out the possible types of roughness evolution.
A roadmap for the generation of benchmarking resources for antimicrobial resistance detection using next generation sequencing
2021-02-08

<ns3:p>Next Generation Sequencing technologies significantly impact the field of Antimicrobial Resistance (AMR) detection and monitoring, with immediate uses in diagnosis and risk assessment. For this application and in general, considerable challenges remain in demonstrating sufficient trust to act upon the meaningful information produced from raw data, partly because of the reliance on bioinformatics pipelines, which can produce different results and therefore lead to different interpretations. With the constant evolution of the field, it is difficult to identify, harmonise and recommend specific methods for large-scale implementations over time. In this article, we propose to address this challenge through establishing a transparent, performance-based, evaluation approach to provide flexibility in the bioinformatics tools of choice, while demonstrating proficiency in meeting common performance standards. The approach is two-fold: first, a community-driven effort to establish and maintain “live” (dynamic) benchmarking platforms to provide relevant performance metrics, based on different use-cases, that would evolve together with the AMR field; second, agreed and defined datasets to allow the pipelines’ implementation, validation, and quality-control over time. Following previous discussions on the main challenges linked to this approach, we provide concrete recommendations and future steps, related to different aspects of the design of benchmarks, such as the selection and the characteristics of the datasets (quality, choice of pathogens and resistances, etc.), the evaluation criteria of the pipelines, and the way these resources should be deployed in the community.</ns3:p>
Emotional arousal enhances the impact of long-term memory in attention
2021-02-08

Research reveals that long-term memory guides attention. However, it remains unclear how it interacts with emotional arousal to guide attention. To address this issue, we asked participants to learn the locations of a target key embedded within scenes (i.e., a training phase). On the next day, participants’ arousal was manipulated by presenting with a previously fear-conditioned tone (CS+) or a neutral tone that had not been paired with electrical stimulation (CS-), followed by the brief presentation of a scene from the training phase. Participants indicated whether the scene included the target key. The target was presented at the same location as in the training phase. Results revealed that CS+, compared with CS-, led to faster target detection, suggesting that arousal induced by CS+ enhanced the effects of long-term memory in guiding attention. These findings support our hypothesis: arousal amplifies the effects of priority in visual search due to long-term memory.
Continental palynomorphs from the Dabaa Formation, North-Western Desert, Egypt: a contribution to the reconstruction of the vegetation on the southern shores of the Tethys Ocean during the Early Oligocene
2021-02-08

Abstract The Eocene–Oligocene transition period was marked by one of the most abrupt and severe global environmental changes in the Cenozoic record, and this had a marked influence on the evolution of a number of animal and plant groups and entire ecosystems. This study documents continental palynomorphs recovered from the sedimentary rocks of the Dabaa Formation (Qattara area, North-Western Desert, Egypt) located on the southern shore of the Tethys Ocean and dated as Late Eocene–Early Oligocene. The botanical affinities, (phyto)ecology and distribution of the vegetation during the Eocene–Oligocene of the study area are discussed. The recorded assemblages are well preserved and comprise diverse lineages of algae, spores and pollen. They were identified, illustrated and assigned to 46 families encompassing chlorococcalean algae, lycopods, ferns, gymnosperms and angiosperms. The studied assemblages demonstrate the development of tropical vegetation, including tropical deciduous forest, grassland and (semi-)arid tropical shrubland, in which angiosperms were one of the main representatives; additionally open, drier habitats might have existed in the hinterland. Our data have been combined with previous megafossil and palynological evidence to assess and refine vegetation changes during the Early Oligocene time window in Egypt and across North Africa. Vegetation was a mosaic of different vegetation belts that ran more-or-less parallel to the coastline of the Tethys Ocean under the variable geographical influence of lagoons and streams. It is assumed that the belt of tropical forest along the coast of the Tethys Ocean narrowed during the Oligocene in parallel to climatic deterioration following the Eocene–Oligocene boundary, which may have also led to the fractionation of forest habitats.
Investor‐state dispute settlement and multinational firm behavior
2021-02-08

Abstract This paper shows that investor‐state dispute settlements (ISDS) make multinational firms more aggressive by increasing cost‐reducing investments with the aim to enlarge the potential compensation an ISDS provision may offer. While a larger investment reduces the market distortion, it will also make potential compensations larger. Consequently, potential compensations to a foreign investor do not imply a zero‐sum game. ISDS may decrease domestic welfare, in particular if the investment leads to the establishment of an export platform, and we find that even global welfare may decline.
Status of clinical research in neurology in Germany—A national survey
2021-02-08

Abstract Background and purpose To provide an overview on the status of clinical research in neurology in Germany. Methods German university hospitals, nonuniversity hospitals, and neurological medical practices were surveyed regarding their clinical research activities during the period 2013 to 2017. Results Fifty percent of university hospitals, 10.6% of nonuniversity hospitals, and 5.2% of medical practices in Germany responded to our questionnaire. More than 80% of the clinical studies conducted have been phase III/IV and noninterventional trials (NISs), whereas &lt;1% have been phase I and 3.5% investigator‐initiated trials (IITs). University hospitals have conducted most of the phase II–IV trials. NISs have been predominantly performed by medical practices. Fifty‐six percent of the university hospitals and less of the nonuniversity institutions confirmed the implementation of standard operating procedures (SOPs). In university hospitals, on average, 11 physicians had acquired a good clinical practice certificate. Overall, 43% of all trials have been performed in neuroimmunology. Conclusions The status of clinical research in neurology in Germany is predominated by NISs and late‐phase trials, potentially due to a general lack of easily accessible funding, which leads to a highly competitive environment and fewer opportunities to perform early‐phase clinical trials as well as IITs. Our results indicate that there is substantial need for structured support for creating and implementing SOPs to maintain quality standards and guarantee uniformity of performance. This survey assessed many aspects of clinical research and serves as guidance for providing ideas for structured improvement of clinical research in neurology in Germany.