julilili42/papers huggingface dataset:
Endocrine-Resistant Breast Cancer: Mechanisms and Treatment
2020-01-01

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Endocrine treatment is one of the most effective therapies for estrogen receptor-positive breast cancer. However, most tumors will develop resistance to endocrine therapy as the cancer progresses. This review focuses on the mechanisms and markers of endocrine-resistant breast cancer. In addition, current and future strategies to overcome endocrine resistance are discussed. &lt;b&gt;&lt;i&gt;Summary:&lt;/i&gt;&lt;/b&gt; Several molecular mechanisms of endocrine resistance have been identified, including alterations in the ESR1 gene or in the PIK3CA/mTOR pathway. Meanwhile, CDK4/6, mTOR, and PI3K inhibition have shown to improve the efficacy of endocrine treatment and new promising approaches are being developed. &lt;b&gt;&lt;i&gt;Key Message:&lt;/i&gt;&lt;/b&gt; Overcoming primary or acquired resistance to endocrine treatment remains a major challenge. Since the molecular mechanisms of endocrine resistance are manifold, optimal combination and sequencing strategies will have to be developed in the future.
Evidence of SARS-CoV2 Entry Protein ACE2 in the Human Nose and Olfactory Bulb
2020-01-01

Usually, pandemic COVID-19 disease, caused by SARS-CoV2, presents with mild respiratory symptoms such as fever, cough, but frequently also with anosmia and neurological symptoms. Virus-cell fusion is mediated by angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) with their organ expression pattern determining viral tropism. Clinical presentation suggests rapid viral dissemination to the central nervous system leading frequently to severe symptoms including viral meningitis. Here, we provide a comprehensive expression landscape of ACE2 and TMPRSS2 proteins across human postmortem nasal and olfactory tissue. Sagittal sections through the human nose complemented with immunolabelling of respective cell types represent different anatomically defined regions including olfactory epithelium, respiratory epithelium of the nasal conchae and the paranasal sinuses along with the hardly accessible human olfactory bulb. ACE2 can be detected in the olfactory epithelium as well as in the respiratory epithelium of the nasal septum, the nasal conchae, and the paranasal sinuses. ACE2 is located in the sustentacular cells and in the glandular cells in the olfactory epithelium as well as in the basal cells, glandular cells, and epithelial cells of the respiratory epithelium. Intriguingly, ACE2 is not expressed in mature or immature olfactory receptor neurons and basal cells in the olfactory epithelium. Similarly, ACE2 is not localized in the olfactory receptor neurons albeit the olfactory bulb is positive. Vice versa, TMPRSS2 can also be detected in the sustentacular cells and the glandular cells of the olfactory epithelium. Our findings provide the basic anatomical evidence for the expression of ACE2 and TMPRSS2 in the human nose, olfactory epithelium, and olfactory bulb. Thus, they are substantial for future studies that aim to elucidate the symptom of SARS-CoV2 induced anosmia via the olfactory pathway.
Dihydropyrimidine Dehydrogenase Testing prior to Treatment with 5-Fluorouracil, Capecitabine, and Tegafur: A Consensus Paper
2020-01-01

Background: 5-Fluorouracil (FU) is one of the most commonly used cytostatic drugs in the systemic treatment of cancer. Treatment with FU may cause severe or life-threatening side effects and the treatment-related mortality rate is 0.2–1.0%. Summary: Among other risk factors associated with increased toxicity, a genetic deficiency in dihydropyrimidine dehydrogenase (DPD), an enzyme responsible for the metabolism of FU, is well known. This is due to variants in the DPD gene (DPYD). Up to 9% of European patients carry a DPD gene variant that decreases enzyme activity, and DPD is completely lacking in approximately 0.5% of patients. Here we describe the clinical and genetic background and summarize recommendations for the genetic testing and tailoring of treatment with 5-FU derivatives. The statement was developed as a consensus statement organized by the German Society for Hematology and Medical Oncology in cooperation with 13 medical associations from Austria, Germany, and Switzerland. Key Messages: (i) Patients should be tested for the 4 most common genetic DPYD variants before treatment with drugs containing FU. (ii) Testing forms the basis for a differentiated, risk-adapted algorithm with recommendations for treatment with FU-containing drugs. (iii) Testing may optionally be supplemented by therapeutic drug monitoring.
Photocatalytic performance and mechanism insights of a S-scheme g-C3N4/Bi2MoO6 heterostructure in phenol degradation and hydrogen evolution reactions under visible light
2020-01-01

Photocatalysis with sustainable utilization and low cost is an environmentally benign method for the degradation of organic pollutants, but the rational design and fabrication of photocatalysts with high catalytic performance is still an challenge.
First results on low-mass dark matter from the CRESST-III experiment
2020-01-01

Abstract The CRESST experiment (Cryogenic Rare Even Search with Superconducting Thermometers), located at Laboratori Nazionali del Gran Sasso in Italy, searches for dark matter particles via their elastic scattering off nuclei in a target material. The CRESST target consists of scintillating CaWO 4 crystals, which are operated as cryogenic calorimeters at millikelvin temperatures. Each interaction in the CaWO 4 target crystal produces a phonon signal and a light signal that is measured by a second cryogenic calorimeter. Since the CRESST-II result in 2015, the experiment is leading the field of direct dark matter search for dark matter masses below 1.7 GeV/ c 2 , extending the reach of direct searches to the sub-GeV/ c 2 mass region. For CRESST-III, whose Phase 1 started in July 2016, detectors have been optimized to reach the performance required to further probe the low-mass region with unprecedented sensitivity. In this contribution the achievements of the CRESST-III detectors will be discussed together with preliminary results and perspectives of Phase 1.
The genus Micromonospora as a model microorganism for bioactive natural product discovery
2020-01-01

We explore the genus <italic>Micromonospora</italic> as a model for natural product research and the discovery progress from the classical bioassay-guided approaches through to the application of genome mining and genetic engineering techniques that target specific products.
Historical experiences: A framework for encountering complex historical sources
2020-01-01

We encounter information about the past in everyday life through films, books and complex historical sources – such as historic sites or eyewitness accounts. Investigations of how visitors and learners engage with these complex historical sources have mainly focused on the ‘something special’ of the encounter on the one hand and on the clear cognitive engagement on the other. Yet, we know little about what and how learners and visitors learn from these complex historical sources and the resultant historical experiences. However, it is an important precondition for further theoretical and empirical research to fully understand these experiences. This article takes the first step in building an integrated model to understand from a situated embodied perspective the historical experiences derived from encounters with complex historical sources. Drawing on German- and English-language literature across related disciplines, we conceptualized the experience within an interplay of cognitive, affective and physical engagement. Within these dimensions, we identified responses that indicate the different elements of the historical experience and discuss limitations and avenues for further research.
Improving robustness against common corruptions by covariate shift adaptation
2020-01-01

Today's state-of-the-art machine vision models are vulnerable to image corruptions like blurring or compression artefacts, limiting their performance in many real-world applications. We here argue that popular benchmarks to measure model robustness against common corruptions (like ImageNet-C) underestimate model robustness in many (but not all) application scenarios. The key insight is that in many scenarios, multiple unlabeled examples of the corruptions are available and can be used for unsupervised online adaptation. Replacing the activation statistics estimated by batch normalization on the training set with the statistics of the corrupted images consistently improves the robustness across 25 different popular computer vision models. Using the corrected statistics, ResNet-50 reaches 62.2% mCE on ImageNet-C compared to 76.7% without adaptation. With the more robust DeepAugment+AugMix model, we improve the state of the art achieved by a ResNet50 model up to date from 53.6% mCE to 45.4% mCE. Even adapting to a single sample improves robustness for the ResNet-50 and AugMix models, and 32 samples are sufficient to improve the current state of the art for a ResNet-50 architecture. We argue that results with adapted statistics should be included whenever reporting scores in corruption benchmarks and other out-of-distribution generalization settings.
<p>Burden of Illness in Geographic Atrophy: A Study of Vision-Related Quality of Life and Health Care Resource Use</p>
2020-01-01

Patients with GA experience a poorer level of vision-related function and QoL than their peers, especially in relation to driving. GA is also associated with notable HCRU/associated costs, mostly direct costs attributed to diagnostic tests/procedures.
3D mapping of soil organic carbon content and soil moisture with multiple geophysical sensors and machine learning
2020-01-01

Abstract Soil organic C (SOC) and soil moisture (SM) affect the agricultural productivity of soils. For sustainable food production, knowledge of the horizontal as well as vertical variability of SOC and SM at field scale is crucial. Machine learning models using depth‐related data from multiple electromagnetic induction (EMI) sensors and a gamma‐ray spectrometer can provide insights into this variability of SOC and SM. In this work, we applied weighted conditioned Latin hypercube sampling to calculate 25 representative soil profile locations based on geophysical measurements on the surveyed agricultural field, for sampling and modeling. Ten additional random profiles were used for independent model validation. Soil samples were taken from four equal depth increments of 15 cm each. These were used to approximate polynomial and exponential functions to reproduce the vertical trends of SOC and SM as soil depth functions. We modeled the function coefficients of the soil depth functions spatially with Cubist and random forests with the geophysical measurements as environmental covariates. The spatial prediction of the depth functions provides three‐dimensional (3D) maps of the field scale. The main findings are (a) the 3D models of SOC and SM had low errors; (b) the polynomial function provided better results than the exponential function, as the vertical trends of SOC and SM did not decrease uniformly; and (c) the spatial prediction of SOC and SM with Cubist provided slightly lower error than with random forests. Hence, we recommend modeling the second‐degree polynomial with Cubist for 3D prediction of SOC and SM at field scale.
An open-label, single-arm, phase II trial of buparlisib in patients with melanoma brain metastases not eligible for surgery or radiosurgery—the BUMPER study
2020-01-01

Abstract Background Patients with melanoma brain metastasis (MBM) still carry a dismal prognosis. Preclinical data originated in xenograft models showed that buparlisib therapy was highly effective in therapy-naïve MBM. Patients and Methods In this open-label, phase II trial, we investigate the safety and efficacy of monotherapy with buparlisib, a PI3K inhibitor, in patients with asymptomatic MBM who were not candidates for local therapy. These patients had also progressed under immunotherapy if BRAF wild-type or under targeted therapy with BRAF/MEK inhibitors if carrying a BRAFV600E/K mutation. The primary endpoint was the intracranial disease control rate assessed by the investigators. The secondary endpoints were overall response rate, duration of response (DOR) of intracranial disease, overall response, progression-free survival (PFS), overall survival (OS), safety, and tolerability of buparlisib. Results A total of 20 patients were screened and 17 patients were treated with buparlisib. Twelve patients had progressed under more than 2 systemic therapy lines and 17 had received at least 1 previous local therapy. There were no intracranial responses. Three patients achieved intracranial stable disease; the median DOR was 117 days. The median PFS was 42 days (95% confidence interval [CI]: 23–61 days) and the median OS was 5.0 months (95% CI: 2.24–7.76 months). No new safety signs were observed. Conclusions Buparlisib was well tolerated but no intracranial responses were observed. These results might be explained in part by the inclusion of only heavily pretreated patients. However, preclinical data strongly support the rationale to explore PI3K inhibitor-based combinations in patients with MBM displaying hyperactivation of the PI3K–AKT pathway.
P4-MACsec: Dynamic Topology Monitoring and Data Layer Protection With MACsec in P4-Based SDN
2020-01-01

We propose P4-MACsec to protect network links between P4-based SDN switches through automated deployment of MACsec, a widespread IEEE standard for securing Layer 2 infrastructures. MACsec is supported by switches and routers from many manufacturers. On these devices, it has only little performance limitations compared to VPN technologies such as IPsec. P4-MACsec suggests a data plane implementation of MACsec including AES-GCM encryption and decryption directly on P4 targets. P4-MACsec features a two-tier control plane structure where local controllers running on the P4 targets interact with a central controller. We propose a novel secure link discovery mechanism that leverages protected LLDP frames and a two-tier control plane structure for secure and efficient management of a global link map. Automated deployment of MACsec creates secure channels, generates keying material, and configures the P4 targets for each detected link between two P4 targets. It detects link changes and performs rekeying to provide a secure, configuration-free operation of MACsec. In this paper, we review the technological background of P4-MACsec and explain its architecture. To demonstrate the feasibility of P4-MACsec, we implement it on the BMv2 P4 software target, validate the prototype through experiments, and evaluate its performance through experiments considering TCP goodput and round-trip time. We publish the prototype and experiment setup under the Apache v2 license on GitHub [7].
Parallel Channels for Motion Feature Extraction in the Pretectum and Tectum of Larval Zebrafish
2020-01-01

Non-cortical visual areas in vertebrate brains extract relevant stimulus features, such as motion, object size, and location, to support diverse behavioral tasks. The optic tectum and pretectum, two primary visual areas in zebrafish, are involved in motion processing, and yet their differential neural representation of behaviorally relevant visual features is unclear. Here, we characterize receptive fields (RFs) of motion-sensitive neurons in the diencephalon and midbrain. We show that RFs of many pretectal neurons are large and sample the lower visual field, whereas RFs of tectal neurons are mostly small-size selective and sample the upper nasal visual field more densely. Furthermore, optomotor swimming can reliably be evoked by presenting forward motion in the lower temporal visual field alone, matching the lower visual field bias of the pretectum. Thus, tectum and pretectum extract different visual features from distinct regions of visual space, which is likely a result of their adaptations to hunting and optomotor behavior, respectively.
Is it possible to identify ancient wine production using biomolecular approaches?
2020-01-01

Chemical analysis of archaeological artefacts is used with increasing regularity to understand how wine was produced, traded, and consumed in the past and to shed light on its antiquity. Based both on an extensive review of the published literature and on new analyses, here we critically evaluate the diverse range of methodological approaches that have been used for wine identification. Overall, we conclude that currently none of the proposed chemical ‘biomarkers’ for wine provide unequivocal evidence. Nevertheless, valid interpretations may be offered if systematically supported by additional contextual data, such as archaeobotanical evidence. We found the extraction and detection method to be particularly crucial for successful identification. We urge the use of controls and quantification to rule out false positives. DNA sequencing offers potential for identifying wine and provides much higher taxonomic resolution, but work is needed to determine the limits of DNA survival on artefacts.
Qualitative analysis of cognitive and social congruence in peer-assisted learning – The perspectives of medical students, student tutors and lecturers
2020-01-01

Cognitive and social congruence may be displayed on the practical behavioural level. Trust in student tutor could be found in both concepts on different levels. The qualitative results provide a deeper insight by indicating that the student tutors may play a 'mediator' role for the relationship between students and lectures.
Compilation of Escherichia coli K-12 outer membrane phage receptors – their function and some historical remarks
2020-01-01

ABSTRACT Many Escherichia coli phages have been sequenced, but in most cases their sequences alone do not suffice to predict their host specificity. Analysis of phage resistant E. coli K-12 mutants have uncovered a certain set of outer membrane proteins and polysaccharides as receptors. In this review, a compilation of E. coli K12 phage receptors is provided and their functional characterization, often driven by studies on phage resistant mutants, is discussed in the historical context. While great progress has been made in this field thus far, several proteins in the outer membrane still await characterization as phage receptors.
Weight Stigma Experiences and Physical (In)activity: A Biographical Analysis
2020-01-01

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; People with obesity often report experiences of weight-related discrimination. In order to find out how such experiences throughout the life course are related to physical activity behavior, we exploratively studied activity-related biographies of people with obesity from a social constructivist perspective. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; We collected biographical data of 30 adults (mean age 37.66 years; 14 males and 16 females) with obesity (average BMI 40.64, including a range from 33 to 58) using a biography visualization tool that allows participants to map developmental courses and critical life experiences over their life course. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Participants remembered a continuous decrease of physical activity from childhood to mid-adulthood. Weight-related discrimination, both in sport and non-sport settings, was especially experienced in adolescence and mid-adulthood. Against the background of our findings, we assume that the degree of felt stigma rather than the stigmatizing behavior itself influences physical activity behavior over the life course. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; The results of our exploratory study reiterate the detrimental effect weight stigma can have on health behaviors. Initiatives are needed to reduce weight stigma in exercise contexts; additionally, initiatives to promote physical activity should focus on helping individuals with obesity to establish coping strategies to reduce the experienced burden from weight stigma.
The Predictive Validity of Teachers’ Personality, Cognitive and Academic Abilities at the End of High School on Instructional Quality in Germany: A Longitudinal Study
2020-01-01

The present study investigated to what degree teachers’ personality traits, cognitive abilities, and academic abilities (high school GPA), which were assessed at the end of high school as well as grades from the first and second state examinations of teacher education, predict later instructional quality. The study combined ratings of instructional quality from 3,768 German secondary school students and their 113 teachers with up to 10 years between assessment of teachers’ personality traits, cognitive abilities, as well as academic abilities at the end of high school and student ratings of instructional quality. Multilevel regression analyses revealed that agreeableness, high school GPA, and the second state examination grade predicted teachers’ instructional quality.
Psychopathological Networks in Cognitive-Behavioral Treatments for Binge-Eating Disorder
2020-01-01

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Network approaches to psychopathology posit that mental disorders emerge from interrelated symptoms, and thus connectivity among symptoms are assumed to negatively predict the treatment response and decrease with efficacious treatment. &lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; This study uniquely sought to elucidate the network structure, its change, and its predictive value in cognitive-behavioral therapy (CBT) for binge-eating disorder (BED). &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; In a multicenter randomized trial of face-to-face and Internet-based guided self-help CBT, 178 individuals with full syndrome and subsyndromal BED, eating disorder and general psychopathology, and body mass index (BMI) were subjected to Gaussian Graphical Network and Exploratory Graph Analyses before and after treatment and at 6-month follow-up. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; At pretreatment, 3 network communities of: eating disorder psychopathology; general psychopathology; and restraint and BMI were identified, with the latter community included in the first thereafter. Eating disorder-related impairment and self-esteem were the most central symptoms, while BMI and binge eating had the lowest centrality. Network connectivity significantly increased from pre- to posttreatment, with the greatest increases in strength centrality found in binge eating and shape concern, but it did not predict remission from binge eating. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; With decreasing symptom severity, CBT resulted in a greater integration and connectivity of the psychopathology network in BED, suggesting an increased patient understanding of relations between binge eating and other symptoms. Network connectivity was not a negative prognostic indicator of treatment outcome. These results indicate a need for further research on the predictive value of network variables in the explanation of therapeutic change for patients with BED.
Carbonyl group and carbon dioxide activation by rare-earth-metal complexes
2020-01-01

Not just hilariously effective baits! Rare-earth-metal compounds selectively react with aldehydes, ketones and carbon dioxide to generate isolable compounds as crucial intermediates in organic synthesis and homogenous catalysis.