Miracle-dz/UniFAR-FTUs huggingface dataset:
Advances in Understanding the Pathophysiology of Lacunar Stroke: A Review

Importance Stroke is the second leading cause of death in the world, and nearly one-third of ischemic strokes are lacunar strokes (LSs) or small subcortical infarcts. Although smaller in size, they create large problems, leaving many patients with intellectual and physical disabilities. Because there are limitations in understanding the underlying pathophysiology of LS, the development of novel therapies has been slow. Observations When the term lacune was described in the 1800s, its underlying pathophysiological basis was obscure. In the 1960s, C. Miller Fisher, MD, performed autopsy studies that showed that vessels supplying lacunes displayed segmental arteriolar disorganization, characterized by vessel enlargement, hemorrhage, and fibrinoid deposition. For these pathologic changes, he coined the term lipohyalinosis. Since that time, few attempts have been made to reconcile this pathologic description with modern mechanisms of cerebral small vessel disease (CSVD). During the past 6 years, progress has been made in understanding the clinical mechanisms, imaging characteristics, and genetic basis of LS. Conclusions and Relevance Questions persist regarding the order of events related to the initiation and progression of CSVD, how LS is related to other sequelae of CSVD, and whether LS is part of a systemic disease process. The relative roles of aging, oxidative stress, mechanical stress, genetic predisposition, and other vascular risk factors should be further studied, especially in the era of widespread antihypertensive use. Although understanding of endothelial dysfunction has increased, future work on the role of media and adventitial dysfunction should be explored. Recent advances in mapping the brain vasculome may generate new hypotheses. The investigation of new therapeutic targets, aimed at reversing CSVD processes and promoting neural repair after LS, depends upon further understanding these basic mechanisms.
The spatial footprint of injection wells in a global compilation of induced earthquake sequences

Seismic limits for hard and soft rock Induced earthquakes from oil, gas, and geothermal energy exploration projects can damage infrastructure and concern the public. However, it remains unclear how far away from an injection site an earthquake can still be triggered. Goebel and Brodsky looked at 18 different earthquake-producing injection sites around the world to address this issue. Injecting fluid into softer layers increased the range for seismic hazard, whereas harder basement rock better confined the fluid. These findings should be considered when regulating and managing projects with the potential to induce seismicity. Science, this issue p. 899 The seismic hazard distance from injection wells is dependent on rock type and fault density. Fluid injection can cause extensive earthquake activity, sometimes at unexpectedly large distances. Appropriately mitigating associated seismic hazards requires a better understanding of the zone of influence of injection. We analyze spatial seismicity decay in a global dataset of 18 induced cases with clear association between isolated wells and earthquakes. We distinguish two populations. The first is characterized by near-well seismicity density plateaus and abrupt decay, dominated by square-root space-time migration and pressure diffusion. Injection at these sites occurs within the crystalline basement. The second population exhibits larger spatial footprints and magnitudes, as well as a power law–like, steady spatial decay over more than 10 kilometers, potentially caused by poroelastic effects. Far-reaching spatial effects during injection may increase event magnitudes and seismic hazard beyond expectations based on purely pressure-driven seismicity.
Quantitative analysis of cell shape and the cytoskeleton in developmental biology

Computational approaches that enable quantification of microscopy data have revolutionized the field of developmental biology. Due to its inherent complexity, elucidating mechanisms of development requires sophisticated analysis of the structure, shape, and kinetics of cellular processes. This need has prompted the creation of numerous techniques to visualize, quantify, and merge microscopy data. These approaches have defined the order and structure of developmental events, thus, providing insight into the mechanisms that drive them. This review describes current computational approaches that are being used to answer developmental questions related to morphogenesis and describe how these approaches have impacted the field. Our intent is not to comprehensively review techniques, but to highlight examples of how different approaches have impacted our understanding of development. Specifically, we focus on methods to quantify cell shape and cytoskeleton structure and dynamics in developing tissues. Finally, we speculate on where the future of computational analysis in developmental biology might be headed.
Narcotic Addiction in Failed Back Surgery Syndrome

Back pain is a common health problem that reduces the quality of life for human beings worldwide. Several treatment modalities have been reported as effective for pain relief. Generally, patients often undergo surgical interventions as pain becomes intractable, after conservative treatment. With advances in surgical techniques, those choosing spinal surgery as an option have increased over time, and instrumentation is more popular than it was years ago. However, some patients still have back pain after spinal operations. The number of patients classified as having failed back surgery syndrome (FBSS) has increased over time as has the requirement for patients receiving long-term analgesics. Because pain relief is regarded as a human right, narcotics were prescribed more frequently than before. Narcotic addiction in patients with FBSS has become an important issue. Here, we review the prevalence of FBSS, the mechanism of narcotic addiction, and their correlations. Additionally, several potentially effective strategies for the prevention and treatment of narcotic addiction in FBSS patients are evaluated and discussed.
PATIENTS WITH EPIRETINAL MEMBRANES DISPLAY RETROGRADE MACULOPATHY AFTER SURGICAL PEELING OF THE INTERNAL LIMITING MEMBRANE.

PURPOSE Intraretinal cystoid spaces are commonly found after surgical peeling of epiretinal membranes. In this study, we explored whether these cysts were associated with ganglion cell loss and thus might be a manifestation of retrograde maculopathy. The latter is a nonvascular edema with a characteristic morphology that is often found in the inner nuclear layer (INL) of patients with optic neuropathy. METHODS In this retrospective case series, we identified consecutive patients who underwent surgical epiretinal membrane peeling. We determined the frequency of microcystic macular edema (MME), defined by vertical cystoid spaces in the INL, and we measured the thickness of individual macular layers before and after surgery. RESULTS Epiretinal membrane peeling resulted in an improvement of visual acuity and a reduction of retinal thickness by about 15%. In total, 35% of patients with MME before surgery showed no sign of MME postoperatively, whereas edema persisted after surgery in 65% of patients. Interestingly, 29% of the patients without MME before surgery developed MME after surgery. Overall, we found MME in 35% of patients before peeling and in 42% after peeling. After surgery, the mean ganglion cell layer thickness was reduced compared with healthy control eyes. Ganglion cell layer thickness correlated inversely with thickness of the INL. Compared with patients without MME, individuals with MME had a thinner ganglion cell layer and a thicker INL in the affected eye. CONCLUSION Our findings indicate that peeling of epiretinal membranes and internal limiting membranes is associated with atrophy of ganglion cells and thickening of the INL. The latter is associated with the presence of MME. Altogether, we assume that surgical treatment of epiretinal membranes induces a variant of a retrograde maculopathy.
Gamifying anatomy education

The objective of our research is to find out if gamification increases motivation for self‐directed learning (SDL) of human anatomy among year 1 medical students, and more importantly, their academic grades (n = 120). At the NUS Yong Loo Lin School of Medicine, anatomy teaching has traditionally been delivered via didactic means. To encourage more active learning, suitable games (non‐digital) and the script concordance test were utilized to enhance the process. The flipped classroom approach was also introduced to further trigger active learning. In addition, the use of mobile apps (digital) was also initiated as supplements for SDL. Feedback was collected based on the previously validated PRO‐SDL scale. Results from the research yielded inconclusive evidence to support enhanced motivation among our students due to gamification (P > 0.05). However, it did help to encourage active participation for a “fun learning” experience supported by numerous positive comments. More importantly, the participant's continuous assessment (CA1, CA2, and CA3) and objective specific practical exam results were better than the cohort's average (P < 0.05), suggesting that enhanced meta‐cognition, and factual recall had taken place. While it is positive, there are some caveats to note with gamification, first and foremost, that it is tutor dependent. Taken together, gamification could represent a new paradigm for anatomy education, and also an opportune time to change the prevailing culture in the healthcare and education industry. Clin. Anat. 31:997–1005, 2018. © 2018 Wiley Periodicals, Inc.
Asheetoxy: A Taxonomy for Classifying Negative Spreadsheet-related Phenomena

Spreadsheets (sometimes also called Excel programs) are powerful tools which play a business-critical role in many organizations. However, due to faulty spreadsheets many bad decisions have been taken in recent years. Since then, a number of researchers have been studying spreadsheet errors. However, one issue that hinders discussion among researchers and professionals is the lack of a commonly accepted taxonomy. Albeit a number of taxonomies for spreadsheet errors have been proposed in previous work, a major issue is that they use the term error that itself is already ambiguous. Furthermore, to apply most existing taxonomies, detailed knowledge about the underlying process and knowledge about the "brain state" of the acting spreadsheet users is required. Due to these limitations, known error-like phenomena in freely available spreadsheet corpora cannot be classified with these taxonomies. We propose Asheetoxy, a simple and phenomenon-oriented taxonomy that avoids the problematic term error altogether. An initial study with 7 participants indicates that even non-spreadsheet researchers similarly classify real-world spreadsheet phenomena using Asheetoxy.
Towards a Better Metric for Evaluating Question Generation Systems

There has always been criticism for using n-gram based similarity metrics, such as BLEU, NIST, etc, for evaluating the performance of NLG systems. However, these metrics continue to remain popular and are recently being used for evaluating the performance of systems which automatically generate questions from documents, knowledge graphs, images, etc. Given the rising interest in such automatic question generation (AQG) systems, it is important to objectively examine whether these metrics are suitable for this task. In particular, it is important to verify whether such metrics used for evaluating AQG systems focus on answerability of the generated question by preferring questions which contain all relevant information such as question type (Wh-types), entities, relations, etc. In this work, we show that current automatic evaluation metrics based on n-gram similarity do not always correlate well with human judgments about answerability of a question. To alleviate this problem and as a first step towards better evaluation metrics for AQG, we introduce a scoring function to capture answerability and show that when this scoring function is integrated with existing metrics, they correlate significantly better with human judgments. The scripts and data developed as a part of this work are made publicly available.
Terminal heat tolerance in wheat: An overview

Since the beginning of the century, ambient temperatures have increased and are predicted to rise further under climate change. Heat stress is a rigorous threat, particularly during reproductive and grain-filling phases, that results into yield loss. Reductions in dry matter accumulation and grain yield, caused by reduced plant photosynthetic capacity through metabolic limitations and oxidative damage to chloroplasts due to heat stress. Wheat pre-breeding and breeding may be based on secondary traits like chlorophyll content, chlorophyll fluorescence and grain number under heat stress. On the other hand, grain yield under heat stress can be improved by selecting genotypes for the rate of grain filling and for grain size. Wheat varieties with improved grain yield can be developed by integrating physiology and biotechnological tools with conventional breeding techniques during reproductive and grain-filling phases. In this review, we have discussed the effect of heat stress on wheat reproductive and grain-filling stages and the strategies to improve terminal heat stress tolerance in wheat.
Radionuclides in the lichen-caribou-human food chain near uranium mining operations in northern Saskatchewan, Canada.

The richest uranium ore bodies ever discovered (Cigar Lake and McArthur River) are presently under development in northeastern Saskatchewan. This subarctic region is also home to several operating uranium mines and aboriginal communities, partly dependent upon caribou for subsistence. Because of concerns over mining impacts and the efficient transfer of airborne radionuclides through the lichen-caribou-human food chain, radionuclides were analyzed in tissues from 18 barren-ground caribou (Rangifer tarandus groenlandicus). Radionuclides included uranium (U), radium (226Ra), lead (210Pb), and polonium (210Po) from the uranium decay series; the fission product (137Cs) from fallout; and naturally occurring potassium (40K). Natural background radiation doses average 2-4 mSv/year from cosmic rays, external gamma rays, radon inhalation, and ingestion of food items. The ingestion of 210Po and 137Cs when caribou are consumed adds to these background doses. The dose increment was 0.85 mSv/year for adults who consumed 100 g of caribou meat per day and up to 1.7 mSv/year if one liver and 10 kidneys per year were also consumed. We discuss the cancer risk from these doses. Concentration ratios (CRs), relating caribou tissues to lichens or rumen (stomach) contents, were calculated to estimate food chain transfer. The CRs for caribou muscle ranged from 1 to 16% for U, 6 to 25% for 226Ra, 1 to 2% for 210Pb, 6 to 26% for 210Po, 260 to 370% for 137Cs, and 76 to 130% for 40K, with 137Cs biomagnifying by a factor of 3-4. These CRs are useful in predicting caribou meat concentrations from the lichens, measured in monitoring programs, for the future evaluation of uranium mining impacts on this critical food chain. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6Figure 7Figure 8Figure 9
New horizons in the compression of functional decline

Abstract Population ageing, which has come about through the combination of increases in life expectancy, larger post-war cohorts reaching older age and reductions in fertility, is challenging societies and particularly health and care providers, worldwide. In Europe, the USA and Japan, there have been increases in years spent with disability and dependency. The majority of such research, as well as professional health and social care practice, measures loss of functional capability or need for social care, by aggregate disability scores, based around activities of daily living and instrumental activities of daily living. Although useful for defining whether an individual has passed a threshold, aggregate scores obscure how functional decline unfolds, and therefore where early intervention might improve intrinsic capacity and reverse or slow down decline, or maintain function. We propose a framework, the compression of functional decline (CFD), based on the latest understanding of the hierarchy of age-related functional decline, which has the potential to (i) help people understand how to live better for longer, (ii) allow the various stakeholders to be able to measure, at a population level, whether that is happening and (iii) identify which interventions are most effective at which stages. CFD is coherent with the World Health Organisation’s Healthy Ageing model and is more easily understood by stakeholders and older people themselves, than current indicators such as frailty. CFD thus provides a realistic view of age-related functional decline in the context of modifiable behaviour to counter widespread public misconceptions about ageing and inform improvements.
In vitro and in vivo phosphorylation of the Cav2.3 voltage-gated R-type calcium channel

ABSTRACT During the recording of whole cell currents from stably transfected HEK-293 cells, the decline of currents carried by the recombinant human Cav2.3+β3 channel subunits is related to adenosine triphosphate (ATP) depletion after rupture of the cells. It reduces the number of functional channels and leads to a progressive shift of voltage-dependent gating to more negative potentials (Neumaier F., et al., 2018). Both effects can be counteracted by hydrolysable ATP, whose protective action is almost completely prevented by inhibition of serine/threonine but not tyrosine or lipid kinases. These findings indicate that ATP promotes phosphorylation of either the channel or an associated protein, whereas dephosphorylation during cell dialysis results in run-down. Protein phosphorylation is required for Cav2.3 channel function and could directly influence the normal features of current carried by these channels. Therefore, results from in vitro and in vivo phosphorylation of Cav2.3 are summarized to come closer to a functional analysis of structural variations in Cav2.3 splice variants.
Interactive implementations of thermodynamics-based RNA structure and RNA–RNA interaction prediction approaches for example-driven teaching

The investigation of RNA-based regulation of cellular processes is becoming an increasingly important part of biological or medical research. For the analysis of this type of data, RNA-related prediction tools are integrated into many pipelines and workflows. In order to correctly apply and tune these programs, the user has to have a precise understanding of their limitations and concepts. Within this manuscript, we provide the mathematical foundations and extract the algorithmic ideas that are core to state-of-the-art RNA structure and RNA–RNA interaction prediction algorithms. To allow the reader to change and adapt the algorithms or to play with different inputs, we provide an open-source web interface to JavaScript implementations and visualizations of each algorithm. The conceptual, teaching-focused presentation enables a high-level survey of the approaches, while providing sufficient details for understanding important concepts. This is boosted by the simple generation and study of examples using the web interface available at http://rna.informatik. uni-freiburg.de/Teaching/. In combination, we provide a valuable resource for teaching, learning, and understanding the discussed prediction tools and thus enable a more informed analysis of RNA-related effects.
Encoding canonical DNA quadruplex structure

The remarkable architectural diversity of four-stranded DNA known as G-quadruplexes can be rationally designed. The main challenge in DNA quadruplex design is to encode a three-dimensional structure into the primary sequence, despite its multiple, repetitive guanine segments. We identify and detail structural elements describing all 14 feasible canonical quadruplex scaffolds and demonstrate their use in control of design. This work outlines a new roadmap for implementation of targeted design of quadruplexes for material, biotechnological, and therapeutic applications.
2005: an EPA odyssey.

MobilomeFINDER (http://mml.sjtu.edu.cn/Mobilome FINDER) is an interactive online tool that facilitates bacterial genomic island or ‘mobile genome’ (mobilome) discovery; it integrates the ArrayOme and tRNAcc software packages. ArrayOme utilizes a microarray-derived comparative genomic hybridization input data set to generate ‘inferred contigs’ produced by merging adjacent genes classified as ‘present’. Collectively these ‘fragments’ represent a hypothetical ‘microarray-visualized genome (MVG)’. ArrayOme permits recognition of discordances between physical genome and MVG sizes, thereby enabling identification of strains rich in microarrayelusive novel genes. Individual tRNAcc tools facilitate automated identification of genomic islands by comparative analysis of the contents and contexts of tRNA sites and other integration hotspots in closely related sequenced genomes. Accessory tools facilitate design of hotspot-flanking primers for in silico and/or wet-science-based interrogation of cognate loci in unsequenced strains and analysis of islands for features suggestive of foreign origins; island-specific and genome-contextual features are tabulated and represented in schematic and graphical forms. To date we have used MobilomeFINDER to analyse several Enterobacteriaceae, Pseudomonas aeruginosa and Streptococcus suis genomes. MobilomeFINDER enables high-throughput island identification and characterization through increased exploitation of emerging sequence data and PCR-based profiling of unsequenced test strains; subsequent targeted yeast recombination-based capture permits fulllength sequencing and detailed functional studies of novel genomic islands.
DP-ADMM: ADMM-Based Distributed Learning With Differential Privacy

Alternating direction method of multipliers (ADMM) is a widely used tool for machine learning in distri-buted settings where a machine learning model is trained over distributed data sources through an interactive process of local computation and message passing. Such an iterative process could cause privacy concerns of data owners. The goal of this paper is to provide differential privacy for ADMM-based distributed machine learning. Prior approaches on differentially private ADMM exhibit low utility under high privacy guarantee and assume the objective functions of the learning problems to be smooth and strongly convex. To address these concerns, we propose a novel differentially private ADMM-based distributed learning algorithm called DP-ADMM, which combines an approximate augmented Lagrangian function with time-varying Gaussian noise addition in the iterative process to achieve higher utility for general objective functions under the same differential privacy guarantee. We also apply the moments accountant method to analyze the end-to-end privacy loss. The theoretical analysis shows that the DP-ADMM can be applied to a wider class of distributed learning problems, is provably convergent, and offers an explicit utility-privacy tradeoff. To our knowledge, this is the first paper to provide explicit convergence and utility properties for differentially private ADMM-based distributed learning algorithms. The evaluation results demonstrate that our approach can achieve good convergence and model accuracy under high end-to-end differential privacy guarantee.