julilili42/papers huggingface dataset:
Adverse Childhood Experiences and the Risk of Coronary Heart Disease in Adulthood: Examining Potential Psychological, Biological, and Behavioral Mediators in the Whitehall II Cohort Study
2021-05-03

Background This study investigated potential psycho‐bio‐behavioral mediators of the association between adverse childhood experiences (ACEs) and the risk of coronary heart disease (CHD) in adulthood. Methods and Results Participants were 5610 British civil servants (mean age, 55.5; 28% women) from the Whitehall II cohort study without CHD at baseline in 1997 to 1999 (wave 5) when retrospective data on the number of ACEs were collected via questionnaire (range, 0–8). Potential mediators assessed at wave 5 included depression and anxiety symptoms, health behaviors (smoking, alcohol dependence, sleep, and physical activity), and cardiometabolic dysregulations. New diagnoses of CHD (myocardial infarction, definite angina, coronary artery bypass grafting, or percutaneous transluminal coronary angioplasty) were assessed from wave 6 (2001) to wave 11 (2012–2013). Logistic regressions examined associations between ACEs, potential mediators, and CHD during the follow‐up period. Natural indirect effects were examined using mediation analysis. A total of 566 (10.1%) participants developed CHD during the follow‐up period. ACEs were associated with an increased likelihood of CHD (odds ratio per ACE, 1.09; 95% CI, 1.00–1.19). Controlling for age and sex, mediation analyses revealed an indirect effect of depression symptoms (natural indirect effects, 1.05; 95% CI, 1.03–1.07), anxiety symptoms (natural indirect effects, 1.12; 95% CI, 1.10–1.15), and a greater number of cardiometabolic dysregulations (natural indirect effects, 1.02; 95% CI, 1.01–1.03) in the association between ACEs and incident CHD. Behavioral factors were not statistically significant mediators. Conclusions Depression symptoms, anxiety symptoms, and cardiometabolic dysregulations partially mediated the association between ACEs and CHD. Regular screening and treatment of symptoms of psychological disorders and cardiometabolic dysregulations may help mitigate the long‐term health burden of ACEs.
Genomewide Association Studies of LRRK2 Modifiers of Parkinson's Disease
2021-05-03

Objective The aim of this study was to search for genes/variants that modify the effect of LRRK2 mutations in terms of penetrance and age‐at‐onset of Parkinson's disease. Methods We performed the first genomewide association study of penetrance and age‐at‐onset of Parkinson's disease in LRRK2 mutation carriers (776 cases and 1,103 non‐cases at their last evaluation). Cox proportional hazard models and linear mixed models were used to identify modifiers of penetrance and age‐at‐onset of LRRK2 mutations, respectively. We also investigated whether a polygenic risk score derived from a published genomewide association study of Parkinson's disease was able to explain variability in penetrance and age‐at‐onset in LRRK2 mutation carriers. Results A variant located in the intronic region of CORO1C on chromosome 12 (rs77395454; p value = 2.5E‐08, beta = 1.27, SE = 0.23, risk allele: C) met genomewide significance for the penetrance model. Co‐immunoprecipitation analyses of LRRK2 and CORO1C supported an interaction between these 2 proteins. A region on chromosome 3, within a previously reported linkage peak for Parkinson's disease susceptibility, showed suggestive associations in both models (penetrance top variant: p value = 1.1E‐07; age‐at‐onset top variant: p value = 9.3E‐07). A polygenic risk score derived from publicly available Parkinson's disease summary statistics was a significant predictor of penetrance, but not of age‐at‐onset. Interpretation This study suggests that variants within or near CORO1C may modify the penetrance of LRRK2 mutations. In addition, common Parkinson's disease associated variants collectively increase the penetrance of LRRK2 mutations. ANN NEUROL 2021;90:82–94
cGMP signalling in dorsal root ganglia and the spinal cord: Various functions in development and adulthood
2021-05-03

Cyclic GMP (cGMP) is a second messenger that regulates numerous physiological and pathophysiological processes. In recent years, more and more studies have uncovered multiple roles of cGMP signalling pathways in the somatosensory system. Accumulating evidence suggests that cGMP regulates different cellular processes from embryonic development through to adulthood. During embryonic development, a cGMP‐dependent signalling cascade in the trunk sensory system is essential for axon bifurcation, a specific form of branching of somatosensory axons. In adulthood, various cGMP signalling pathways in distinct cell populations of sensory neurons and dorsal horn neurons in the spinal cord play an important role in the processing of pain and itch. Some of the involved enzymes might serve as a target for future therapies. In this review, we summarise the knowledge regarding cGMP‐dependent signalling pathways in dorsal root ganglia and the spinal cord during embryonic development and adulthood, and the potential of targeting these pathways. LINKED ARTICLES This article is part of a themed issue on cGMP Signalling in Cell Growth and Survival. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.11/issuetoc
Targeted Phosphoinositides Analysis Using High-Performance Ion Chromatography-Coupled Selected Reaction Monitoring Mass Spectrometry
2021-05-03

Phosphoinositides are minor components of cell membranes, but play crucial roles in numerous signal transduction pathways. To obtain quantitative measures of phosphoinositides, sensitive, accurate, and comprehensive methods are needed. Here, we present a quantitative targeted ion chromatography-mass spectrometry-based workflow that separates phosphoinositide isomers and increases the quantitative accuracy of measured phosphoinositides. Besides testing different analytical characteristics such as extraction and separation efficiency, the reproducibility of the developed workflow was also investigated. The workflow was verified in resting and stimulated human platelets, fat cells, and rat hippocampal brain tissue, where the LOD and LOQ for phosphoinositides were at 312.5 and 625 fmol, respectively. The robustness of the workflow is shown with different applications that confirms its suitability to analyze multiple less-abundant phosphoinositides.
Neuro‐oncological patients' and caregivers' psychosocial burden during the COVID‐19 pandemic—A prospective study with qualitative content analysis
2021-05-03

Abstract Objective The COVID‐19 pandemic may reinforce psychosocial distress of neuro‐oncological patients. We aimed to (1) differentiate the burden caused by the pandemic versus the tumor and (2) establish topics relevant for brain tumor patients (BTPs) and caregivers. Methods Patients and caregivers were prospectively assessed from April 2020–July 2020 by a 10‐item comprising interview over the phone, including qualitative and quantitative questions. They were quantitatively evaluated i.a. by the distress thermometer (DT, score 1–10). The qualitative questions were analyzed using structured content analysis: The interview questions defined the main categories. Subcategories were derived by an inductive approach assessing the frequency of patients' and caregivers' answers. Results A total of 69 patients and 20 caregivers were interviewed; n = 36 were female (49%), mean age was 53 years (range 32–81). Patients' disease‐related DT scores were higher than the COVID‐19‐related DT scores: the median of the disease‐related DT score was 7 (range 2–10) versus median of COVID‐19‐related distress: 5.0 (range 2–7). Caregivers perceived a higher burden due to the disease (DT median disease: 8; range 2–10 vs. DT pandemic: 3, range 0–10). A total of five main and 21 subcategories were elaborated, most frequently mentioned were “restrictions in public and private affairs” (28%), “changes in the psychological well‐being” (23%), “limited social interaction by contact restriction” (25%). Subcategories relevant for caregivers were similar to those of BTPs. Conclusion A considerable proportion of patients and caregivers still perceived the brain tumor disease as more burdensome than the pandemic. We established main and subcategories of interview items possibly of great relevance to patients during these difficult times, which could be implemented in the content‐related adaption of the psychosocial assessment.
Update Breast Cancer 2021 Part 1 – Prevention and Early Stages
2021-05-03

Abstract This review summarises not only the latest evidence on prevention, but also the current research on the treatment of early-stage breast cancer patients. Recent years have seen a growing body of evidence on the risk of high- and moderate-penetrance breast cancer susceptibility genes. A large international consortium has now been able to further refine the answer to the question of the significance of the so-called panel genes. Moreover, the data on treatment selection regarding endocrine efficacy and the decision for or against chemotherapy have also been advanced markedly. There is also new data on adjuvant CDK4/6 (cyclin-dependent kinase 4/6) inhibitors, which are standard in first-line treatment in patients with metastatic HER2-negative, hormone receptor-positive (HR+) breast cancer. For other therapies such as immune checkpoint inhibitors, which have successfully improved the rate of pathologic complete response (pCR) in neoadjuvant treatment settings for patients with triple-negative breast cancer (TNBC), there is a growing understanding of the quality of life and side effects. This is especially important in situations where patients could possibly be cured without such a regimen.
Counterfactual Generative Networks
2021-05-03

Neural networks are prone to learning shortcuts -- they often model simple correlations, ignoring more complex ones that potentially generalize better. Prior works on image classification show that instead of learning a connection to object shape, deep classifiers tend to exploit spurious correlations with low-level texture or the background for solving the classification task. In this work, we take a step towards more robust and interpretable classifiers that explicitly expose the task's causal structure. Building on current advances in deep generative modeling, we propose to decompose the image generation process into independent causal mechanisms that we train without direct supervision. By exploiting appropriate inductive biases, these mechanisms disentangle object shape, object texture, and background; hence, they allow for generating counterfactual images. We demonstrate the ability of our model to generate such images on MNIST and ImageNet. Further, we show that the counterfactual images can improve out-of-distribution robustness with a marginal drop in performance on the original classification task, despite being synthetic. Lastly, our generative model can be trained efficiently on a single GPU, exploiting common pre-trained models as inductive biases.
The provision of work–life balance practices across welfare states and industries and their impact on extraordinary turnover
2021-05-03

Abstract This study focusses on the provision of work–life balance practices across welfare states and industries and its effect on extraordinary turnover. Given the welfare states and the industry's differences, it is important to focus on extraordinary employee turnover defined as positive and negative deviations from the relevant means per year and by welfare state and industry. Based on a sample of 199 listed companies in these European welfare states from 2002 to 2011, the results showed that the provision of daycare services is higher in socially oriented welfare states (e.g., Sweden, Germany) or in low‐technology industries (consumer services) than in liberally oriented welfare states (e.g., Italy, the United Kingdom) or in high‐technology industries (e.g., IT). For the provision of daycare services, the findings support a decreasing effect on extraordinary employee turnover, whereas other practices such as flexible working, generous vacations and additional maternity leave have no effect.
Seasonal impact on surgical site infections and wound healing disturbance in carpal tunnel surgery: A retrospective cohort study
2021-05-03

Abstract Carpal tunnel syndrome is the most common entrapment syndrome of a peripheral nerve. The gold standard treatment is open carpal tunnel release which has a high success rate, a low complication rate, and predictable postoperative results. However, it has not been analysed yet if there is a seasonal influence on complications for carpal tunnel release, a highly elective procedure. In this retrospective study, we determine whether there is a seasonal impact on surgical site infections (SSI) and wound healing disorders (WHD) in primary carpal tunnel syndrome surgery. Between 2014 and 2018, we have assessed 1385 patients (65% female, 35% male) at a mean age of 61.9 (SD 15.3) years, which underwent open carpal tunnel release because of primary carpal tunnel syndrome. The seasonal data such as the warm season (defined as the period from 1st of June until 15th of September), the average daily and monthly temperature, and the average relative humidity were analysed. Patient demographics were examined including body mass index, alcohol and nicotine abuse, the use of anticoagulants and antiplatelet drugs as well as comorbidities. These data were correlated regarding their influence to the rate of surgical site infections and wound healing disorders in our study collective. A postoperative SSI rate of 2.4% and a WHD rate of 7% were detected. Our data confirms the warm season, the average monthly temperature, and male sex as risk factors for increasing rates of WHDs. Serious SSIs with subsequent revision surgery could be correlated with higher age and higher relative humidity. However there is no seasonal impact on SSIs. We therefore advise considering the timing of this elective surgery with scheduling older male patients preferably during the cold season to prevent postoperative WHDs.
Muscle fatigue revisited - Insights from optically pumped magnetometers
2021-05-03

Abstract Muscle fatigue is well characterized electromyographically, nevertheless only information about summed potential differences is detectable. In contrast, recently developed quantum sensors optically pumped magnetometers (OPMs) offer the advantage of recording both the electrical current propagation in the muscle as well as its geometry, by measuring the magnetic field generated by the muscular action potentials. Magnetomyographic investigation of muscle fatigue is still lacking and it is an open question whether fatigue is characterized similarly in magnetomyography (MMG) compared to electromyography (EMG). Herein, we investigated the muscle fatigue during a 3×1-min strong isometric contraction of the rectus femoris muscle of 12 healthy subjects using simultaneous EMG-MMG (4-channel surface EMG and 4 OPM along the rectus femoris muscle). Both EMG and MMG showed the characteristic frequency decrease in the signal magnitude during isometric contraction, which is typical for muscle fatigue. In addition, it was shown that the main part of this frequency decrease seems to occur in the circular component of the magnetic field around the muscle fibers and less longitudinally along the muscle fibers. Overall, these results show not only that magnetomyography is capable of reproducing the electromyographic standards in identifying muscular fatigue, but it also adds relevant information about the spatial characterization of the signal. Therefore, OPM-MMG offers new insights for the study of muscular activity and might serve as a new, supplementary neurophysiological method.
Space cannot substitute for time -- an integrated experimental assessment of climate-change effects on litter decomposition
2021-05-03

Litter decomposition, a key component of the global carbon cycle, is greatly affected by climate. Unfortunately, our current understanding of climate-change effects on decomposition stems mainly from space-for-time studies along climate gradients, where biotic and climatic effects on litter decomposition are confounded. Experimental studies separating indirect from direct climate effects are needed that test the validity of the space-for-time approach. Here, we combined large- and small scale reciprocal litter translocations, in situ precipitation manipulation, and a prominent climate gradient for studying drought effects on litter decomposition. Interestingly, all experiments indicated clear positive effects of precipitation on decomposition, but the space-for-time approach indicated the opposite, due to indirect climate effects on litter quality. This indicates that space cannot substitute for time and highlights the need for experimental evidence in litter decomposition studies. Such evidence would improve predictions of models of the global carbon cycle that include interactions between climate and vegetation.
The linguistics of reading literature
2021-05-03

Abstract In this paper, I attempt a bridge between linguistics, in particular text pragmatics, and school reading of literary texts. I propose a linguistic model of these peculiarities of the reading of literary texts, especially poetry, that have been called ‘aesthetic reading’, arguing that a linguistically founded basis is what is lacking for school engagement with (not only literary) texts. In the last years there has been extensive research on the linguistics-literature interface; however, what is surprisingly still missing, is a consistent linguistic model of literary reading. In this paper, I propose such a model and show that ‘aesthetic reading’ involves a distinct reading strategy that can be captured in terms of text-world-models and the differentiation between coherence and text sense displaying. Consciously reading poetry amounts, linguistically seen, to a close reading (i) especially focusing marked expressions, i.e., deviations from phonological, morphological, syntactic, semantic and textpragmatic routines, (ii) maintaining of unsolved ambiguities and thus (iii) generating an array of ‘authorized inferences’ that can be productively used for a principled plurality of interpretations. I specify this proposal and illustrate it with two cases of marked pronominal reference, arguing that my proposal has some important implications that make it particularly suitable for school context.
Generalization in data-driven models of primary visual cortex
2021-05-03

Deep neural networks (DNN) have set new standards at predicting responses of neural populations to visual input. Most such DNNs consist of a convolutional network (core) shared across all neurons which learns a representation of neural computation in visual cortex and a neuron-specific readout that linearly combines the relevant features in this representation. The goal of this paper is to test whether such a representation is indeed generally characteristic for visual cortex, i.e. generalizes between animals of a species, and what factors contribute to obtaining such a generalizing core. To push all non-linear computations into the core where the generalizing cortical features should be learned, we devise a novel readout that reduces the number of parameters per neuron in the readout by up to two orders of magnitude compared to the previous state-of-the-art. It does so by taking advantage of retinotopy and learns a Gaussian distribution over the neuron’s receptive field position. With this new readout we train our network on neural responses from mouse primary visual cortex (V1) and obtain a gain in performance of 7% compared to the previous state-of-the-art network. We then investigate whether the convolutional core indeed captures general cortical features by using the core in transfer learning to a different animal. When transferring a core trained on thousands of neurons from various animals and scans we exceed the performance of training directly on that animal by 12%, and outperform a commonly used VGG16 core pre-trained on imagenet by 33%. In addition, transfer learning with our data-driven core is more data-efficient than direct training, achieving the same performance with only 40% of the data. Our model with its novel readout thus sets a new state-of-the-art for neural response prediction in mouse visual cortex from natural images, generalizes between animals, and captures better characteristic cortical features than current task-driven pre-training approaches such as VGG16.
Distribution of GOPC:ROS1and otherROS1fusions in glioma types
2021-05-03

Abstract The ROS proto-oncogene 1 ( ROS1 ) gene is rearranged in various cancers. The translated fusion protein presents an attractive therapeutic target, since specific inhibitors have been approved for several tumor types. In glioma, ROS1 fusions are frequent within infantile hemispheric glioma, and single case reports on occurrences in other glioma types exist. However, a comprehensive analysis spanning the full width of glioma types and subtypes is lacking. We here assessed the spectrum and distribution of ROS1 fusions by screening &gt;20,000 glioma cases for typical chromosomal alterations, with subsequent RNA-sequencing for confirmation of candidate cases. ROS1 fusions were identified in 16 cases, from low grade pilocytic astrocytoma WHO grade 1 to glioblastoma, IDH wildtype WHO grade 4. Thus, despite being enriched in some tumor types, ROS1 fusions are not pathognomonic for specific glioma types and may consitute a relevant target in a variety of cases.
Cancer immunoediting by melanocyte differentiation antigen-specific T cells determines response to immune checkpoint inhibition
2021-05-03

<title>Abstract</title> T cells are critical in cancer immune surveillance but they can also shape tumor immunogenicity, described as cancer immunoediting. Melanoma patients commonly harbor T cells recognizing melanocyte differentiation antigens (MDAs). However, the roles of MDA-specific T cells in shaping melanoma immunogenicity and the response to immune checkpoint inhibition remain elusive. Here, we prospectively profiled peripheral CD8+ T cells from 27 stage IV patients before initiation of checkpoint inhibitor therapy. Clinical failure was associated with increased MDA-specific CD8+ T cells and reduced tumor MDA expression pretreatment. In nonresponders, decreased tumor MDA expression was concomitant with a dedifferentiated melanoma phenotype. We confirmed in 30 stage III patients that individuals with relapse disease during adjuvant anti-PD-1 therapy demonstrated a significantly higher incidence of dedifferentiated tumors pretreatment than individuals without recurrence. Thus, MDA-directed CD8+ T cells are associated with a dedifferentiated phenotype and reduced clinical response to checkpoint inhibitor therapy suggesting immunoediting as an important resistance mechanism.
Comment on the paper by Buono et al. “Dynamics of degassing in evolved alkaline magmas: Petrological, experimental and theoretical insights” (Earth Science Reviews, 211 (2020), 103402)
2021-05-03

The mountainous, glaciated island of South Georgia is the crest of one of the most isolated fragments of continental crust on Earth. It is located approximately 1700 km east of the southern termination of the Andean Cordillera of South America. The island is primarily composed of Lower Cretaceous turbidites, the infill of a marginal basin floored by stretched continental and ophiolitic crust. Remnants of a volcanic arc are preserved on offshore islands to the southwest. The Pacific hinterland of the southernmost Andes is missing in Tierra del Fuego, terminating at a submarine escarpment forming the continental margin immediately east of Cape Horn. The arc and back-arc basin infill rocks of South Georgia correspond exactly to part of the missing Cordilleran hinterland.The mechanism of transport of the South Georgia microcontinent eastward relative to South America remains obscure, but likely involved some form of 'escape tectonics' during mid- to Late Cretaceous counterclockwise rotation of the arc that led to closure and inversion of the marginal basin.