bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transoral Endoscopic Thyroidectomy Vestibular Approach (TOETVA) in Thyroiditis
Authors: Dinc Bulent , Gunduz Umut R. , Belen Nurhan H. 
Published: September 2020

Background:
Parenchymal fibrosis, which develops in the case of thyroiditis, makes thyroidectomy difficult and increases complication rates. Similar concerns exist within minimally invasive thyroid surgery. This study aimed to evaluate the outcomes of the transoral endoscopic thyroidectomy vestibular approach (TOETVA) procedure in patients with thyroiditis.

Materials and Methods:
The data of 56 patients who underwent TOETVA between February 2018 and March 2020 were analyzed retrospectively. The patients were classified as those who had lymphocytic or Hashimoto thyroiditis (group T) and those who did not (group NT) in the postoperative pathology results. Results were evaluated in terms of intraoperative, postoperative findings, and complications.

Results:
All patients were female individuals with a median age of 43 (21-76). There were 21 (37%) patients in group T and 35 (63%) patients in group NT. Mean operation times were 174.2±37.4 and 201.4±45.6 minutes in groups T and NT (P=0.025), respectively, and were statistically shorter in group T. Blood loss was 37.9±44.5 and 34.6±46.8 mL (P=0.811) in groups T and NT, respectively. Transient recurrent laryngeal nerve palsy occurred in 1 patient (5%) in group T, 1 (3%) in group NT (P=0.712), and transient hypoparathyroidism occurred in 3 patients (14%) in group T and in 7 (20%) in group NT. There was no difference in terms of intraoperative and postoperative complications.

Conclusion:
Although thyroiditis is a condition that complicates thyroidectomy, TOETVA can be applied with similar complication rates in patients with thyroiditis.
Acute Care and Treatment of Migraine
Authors: Konstantinos Spingos , Vikelis Michail , Rapoport Alan 
Published: September 2020

Objective:
Migraine is a chronic neurological disease involving the brain and its vasculature, typically characterized by recurrent attacks of moderate or severe throbbing headache, accompanied by sensitivity to light and sound, and associated with nausea, vomiting, and inability to move due to worsening of pain. About 30% of migraineurs have some type of aura, most often visual. Migraine attacks, if untreated or suboptimally treated, usually result in significant disability, requiring bed rest and resulting in poor quality of life. Increased frequency of attacks and overuse of acute care medication are significant risks for chronification, resulting in the transformation of episodic migraine into chronic migraine. We aim to review most acute care treatments for migraine.

Methods:
Current treatment options for migraine attacks were reviewed from the selected literature and combined with our clinical experience.

Results:
Current acute treatment options for migraine attacks include over-the-counter analgesics, at times combined with caffeine, nonsteroidal anti-inflammatory medications, opioids, and migraine-specific medications such as triptans and ergots. In the near future, we will probably have 3 gepants (small-molecule calcitonin gene-related peptide [CGRP] receptor antagonists). The first one was just approved in the United States. A ditan acting as a stimulator of 5-HT1F receptors, was also just approved by the FDA. Stimulation of the trigeminal, vagal, occipital, and even upper arm peripheral nerves through electrical nerve stimulation devices and magnetic stimulation devices are available as alternative, nondrug treatment options. Several devices have already been FDA-allowed for treatment in the United States and/or approved elsewhere, and others will follow soon. Behavioral medicine techniques such as biofeedback training and mindfulness have been available for some time and are often helpful.

Conclusion:
A wide variety of acute care options to treat migraine are available, and others will soon be and will herein be described in further detail. Some medications have been approved by regulatory authorities in countries other than the United States, and some devices have been given a CE Mark in Europe.
Age-associated epigenetic change in chimpanzees and humans
Authors: Guevara Elaine E. , Lawler Richard R. , Staes Nicky , White Cassandra M. , Sherwood Chet C. , Ely John J. , Hopkins William D. , Bradley Brenda J. 
Published: September 2020

Methylation levels have been shown to change with age at sites across the human genome. Change at some of these sites is so consistent across individuals that it can be used as an ‘epigenetic clock’ to predict an individual's chronological age to within a few years. Here, we examined how the pattern of epigenetic ageing in chimpanzees compares with humans. We profiled genome-wide blood methylation levels by microarray for 113 samples from 83 chimpanzees aged 1–58 years (26 chimpanzees were sampled at multiple ages during their lifespan). Many sites (greater than 65 000) showed significant change in methylation with age and around one-third (32%) of these overlap with sites showing significant age-related change in humans. At over 80% of sites showing age-related change in both species, chimpanzees displayed a significantly faster rate of age-related change in methylation than humans. We also built a chimpanzee-specific epigenetic clock that predicted age in our test dataset with a median absolute deviation from known age of only 2.4 years. However, our chimpanzee clock showed little overlap with previously constructed human clocks. Methylation at CpGs comprising our chimpanzee clock showed moderate heritability. Although the use of a human microarray for profiling chimpanzees biases our results towards regions with shared genomic sequence between the species, nevertheless, our results indicate that there is considerable conservation in epigenetic ageing between chimpanzees and humans, but also substantial divergence in both rate and genomic distribution of ageing-associated sites.
This article is part of the theme issue ‘Evolution of the primate ageing process'.
Differential ageing trajectories in motivation, inhibitory control and cognitive flexibility in Barbary macaques (Macaca sylvanus)
Authors: Rathke Eva-Maria , Fischer Julia 
Published: September 2020

Across the lifespan, the performance in problem-solving tasks varies strongly, owing to age-related variation in cognitive abilities as well as the motivation to engage in a task. Non-human primates provide an evolutionary perspective on human cognitive and motivational ageing, as they lack an insight into their own limited lifetime, and ageing trajectories are not affected by customs and societal norms. To test age-related variation in inhibitory control, cognitive flexibility and persistence, we presented Barbary macaques (Macaca sylvanus), living at La Forêt des Singes in Rocamadour (France), with three problem-solving tasks. We conducted 297 trials with 143 subjects aged 2–30 years. We found no effect of age on success and latency to succeed in the inhibitory control task. In the cognitive flexibility task, 21 out of 99 monkeys were able to switch their strategy, but there was no evidence for an effect of age. Yet, the persistence in the motivation task as well as the overall likelihood to participate in any of the tasks declined with increasing age. These results suggest that motivation declines earlier than the cognitive abilities assessed in this study, corroborating the notion that non-human primates and humans show similar changes in motivation in old age.This article is part of the theme issue ‘Evolution of the primate ageing process'.
Diversity reduces extinction risk at global scales
Authors: Weeks Brian C. , Naeem Shahid , Lasky Jesse R. , Tobias Joseph A. 
Published: September 2020

AbstractIncreases in biodiversity often lead to greater, and less variable, levels of ecosystem functioning. However, whether species are therefore less likely to go extinct in more diverse systems is unclear. We use comprehensive estimates of avian taxonomic, phylogenetic and functional diversity to characterize the global relationship between multiple dimensions of diversity and extinction risk in birds. We find that more diverse assemblages have lower mean IUCN threat status despite being composed of species with attributes that make them more vulnerable to extinction, such as large body size or small range size. Our analyses also reveal that this reduction of current threat status associated with greater diversity far outweighs the increased risk associated with the accumulation of extinction-prone species in more diverse assemblages. These results suggest that species conservation targets can best be achieved by maintaining high levels of overall biodiversity in natural ecosystems.
Comparative gene expression in cells competent in or lacking DNA-PKcs kinase activity following etoposide exposure reveal differences in gene expression associated with histone modifications, inflammation, cell cycle regulation, Wnt signaling, and differentiation
Authors: Ali Sk Imran , Najaf-Panah Mohammad J. , Sena Johnny , Schilkey Faye D. , Ashley Amanda K. 
Published: September 2020

AbstractMaintenance of the genome is essential for cell survival, and impairment of the DNA damage response is associated with multiple pathologies including cancer and neurological abnormalities. DNA-PKcs is a DNA repair protein and a core component of the classical non-homologous end-joining pathway, but it may have roles in modulating gene expression and thus, the overall cellular response to DNA damage. Using cells producing either wild-type (WT) or kinase-inactive (KR) DNA-PKcs, we assessed global alterations in gene expression in the absence or presence of DNA damage. We evaluated differential gene expression in untreated cells and observed differences in genes associated with cellular adhesion, cell cycle regulation, and inflammation-related pathways. Following exposure to etoposide, we compared how KR versus WT cells responded transcriptionally to DNA damage. Downregulation of pathways involved in biosynthesis were observed in both genotypes, but upregulated biological pathways were divergent, again with KR cells manifesting a more robust inflammatory response compared to WT cells. To determine what major transcriptional regulators are controlling the differences in gene expression noted, we used pathway analysis and found that many master regulators of histone modifications, proinflammatory pathways, cell cycle regulation, Wnt/β-catenin signaling, and cellular development and differentiation were impacted by DNA-PKcs status. Overall, our results indicate that DNA-PKcs, in a kinase-dependent fashion, decreases proinflammatory signaling following genotoxic insult. As multiple DNA-PK kinase inhibitors are in clinical trial as cancer therapeutics utilized in combination with DNA damaging agents, understanding the transcriptional response when DNA-PKcs cannot phosphorylate downstream targets will inform the overall patient response to combined treatment.
A framework to efficiently smoothL1penalties for linear regression
Authors: Hahn Georg , Lutz Sharon M. , Laha Nilanjana , Lange Christoph 
Published: September 2020

AbstractPenalized linear regression approaches that include anL1term have become an important tool in statistical data analysis. One prominent example is the least absolute shrinkage and selection operator (Lasso), though the class ofL1penalized regression operators also includes the fused and graphical Lasso, the elastic net, etc. Although theL1penalty makes their objective function convex, it is not differentiable everywhere, motivating the development of proximal gradient algorithms such as Fista, the current gold standard in the literature. In this work, we take a different approach based on smoothing in a fixed parameter setting (the problem sizenand number of parameterspare fixed). The methodological contribution of our article is threefold: (1) We introduce a unified framework to compute closed-form smooth surrogates of a whole class ofL1penalized regression problems using Nesterov smoothing. The surrogates preserve the convexity of the original (unsmoothed) objective functions, are uniformly close to them, and have closed-form derivatives everywhere for efficient minimization via gradient descent; (2) We prove that the estimates obtained with the smooth surrogates can be made arbitrarily close to the ones of the original (unsmoothed) objective functions, and provide explicitly computable a priori error bounds on the accuracy of our estimates; (3) We propose an iterative algorithm to progressively smooth theL1penalty which increases accuracy and is virtually free of tuning parameters. The proposed methodology is applicable to a large class ofL1penalized regression operators, including all the operators mentioned above. Although the resulting estimates are typically dense, sparseness can be enforced again via thresholding. Using simulation studies, we compare our framework to current gold standards such as Fista, glmnet, gLasso, etc. Our results suggest that our proposed smoothing framework provides predictions of equal or higher accuracy than the gold standards while keeping the aforementioned theoretical guarantees and having roughly the same asymptotic runtime scaling.
DNABERT: pre-trained Bidirectional Encoder Representations from Transformers model for DNA-language in genome
Authors: Ji Yanrong , Zhou Zhihan , Liu Han , Davuluri Ramana V 
Published: September 2020

ABSTRACTDeciphering the language of non-coding DNA is one of the fundamental problems in genome research. Gene regulatory code is highly complex due to the existence of polysemy and distant semantic relationship, which previous informatics methods often fail to capture especially in data-scarce scenarios. To address this challenge, we developed a novel pre-trained bidirectional encoder representation, named DNABERT, that forms global and transferrable understanding of genomic DNA sequences based on up and downstream nucleotide contexts. We show that the single pre-trained transformers model can simultaneously achieve state-of-the-art performance on many sequence predictions tasks, after easy fine-tuning using small task-specific data. Further, DNABERT enables direct visualization of nucleotide-level importance and semantic relationship within input sequences for better interpretability and accurate identification of conserved sequence motifs and functional genetic variants. Finally, we demonstrate that pre-trained DNABERT with human genome can even be readily applied to other organisms with exceptional performance.
scIntegral: A scalable and accurate cell-type identification method for scRNA-seq data with application to integration of multiple donors
Authors: Lee Hanbin , Kim Chanwoo , Jeong Juhee , Jung Keehoon , Han Buhm 
Published: September 2020

AbstractWe presentscIntegral, a scalable and accurate method to identify cell types in scRNA data. Our method probabilistically identifies cell-types of the cells in a semi-supervised manner using marker list information as prior. scIntegral is more accurate than existing state-of-the-art methods, reducing the error rate by up to three-folds in real data. scIntegral can precisely identify very rare (<0.5%) cell populations, suggesting utilities forin-silicocell extraction. A notable application of scIntegral is to systematically integrate scRNA-seq data of multiple donors with strong heterogeneity and batch effects. scIntegral is extremely efficient and takes only an hour to integrate ten thousand donor data, while fully accounting for heterogeneity with covariates. Many previous methods focused on integrating multi-sample data in the cluster level, but it was challenging to quantitatively measure the benefit of integration. We show that integrating multiple donors can significantly reduce the error rate in cell-type identification, when measured with respect to the gold standard cell labels. scIntegral is freely available athttps://github.com/hanbin973/scIntegral.
Neural encoding of the reliability of directional information during the preparation of targeted movements
Authors: Tzagarakis Charidimos , West Sarah , Pellizzer Giuseppe 
Published: September 2020

AbstractVisual information about the location of an upcoming target can be used to prepare an appropriate motor response and reduce its reaction time. Here, we investigated the brain mechanisms associated with the reliability of directional information used for motor preparation. We recorded brain activity using magnetoencephalography (MEG) during a delayed reaching task in which a visual cue provided valid information about the location of the upcoming target with 50, 75 or 100% reliability. We found that reaction time increased as cue reliability decreased and that trials with invalid cues had longer reaction times than trials with valid cues. MEG channel analysis showed that during the late cue period the power of the beta-band from left mid-anterior channels, contralateral to the responding hand, correlated with the reliability of the cue. This effect was source localized over a large motor-related cortical and subcortical network. In addition, during invalid-cue trials there was a phasic increase of theta-band power following target onset from left posterior channels, localized to the left occipito-parietal cortex. Furthermore, the theta-beta cross-frequency coupling between left mid-occipital and motor cortex transiently increased before responses to invalid-cue trials. In conclusion, beta-band power in motor-related areas reflected the reliability of directional information used during motor preparation, whereas phasic theta-band activity may have signaled whether the target was at the expected location or not. These results elucidate mechanisms of interaction between attentional and motor processes.
Graded spikes differentially signal neurotransmitter input in cerebrospinal fluid contacting neurons of the mouse spinal cord
Authors: Johnson Emily , Clark Marilyn , Oncul Merve , MacLean Claudia , Deuchars Jim , Deuchars Susan A. , Johnston Jamie 
Published: September 2020

AbstractThe action potential and its all-or-none nature is fundamental to neural communication. Canonically the action potential is initiated once voltage-gated Na+channels are activated, and their rapid kinetics of activation and inactivation give rise to the action potential’s all-or-none nature. Here we show that cerebrospinal fluid contacting neurons (CSFcNs) surrounding the central canal of the mouse spinal cord employ a different strategy. Rather than using voltage-gated Na+channels to generate binary spikes, CSFcNs use two different types of voltage-gated Ca2+channel, enabling spikes of different amplitude. T-type Ca2+channels generate small amplitude spikes, whereas large amplitude spikes require high voltage-activated Cd2+sensitive Ca2+channels. We show that these different amplitude spikes signal input from different transmitter systems; purinergic inputs evoke smaller T-type dependent spikes while cholinergic inputs evoke large T-type independent spikes. Different synaptic inputs to CSFcNs can therefore be signalled by the spike amplitude.
ALPACA: a fast and accurate approach for automated landmarking of three-dimensional biological structures
Authors: Porto Arthur , Rolfe Sara M. , Maga A. Murat 
Published: September 2020

AbstractLandmark-based geometric morphometrics has emerged as an essential discipline for the quantitative analysis of size and shape in ecology and evolution. With the ever-increasing density of digitized landmarks, the possible development of a fully automated method of landmark placement has attracted considerable attention. Despite the recent progress in image registration techniques, which could provide a pathway to automation, three-dimensional morphometric data is still mainly gathered by trained experts. For the most part, the large infrastructure requirements necessary to perform image-based registration, together with its system-specificity and its overall speed have prevented wide dissemination.Here, we propose and implement a general and lightweight point cloud-based approach to automatically collect highdimensional landmark data in 3D surfaces (Automated Landmarking through Point cloud Alignment and Correspondence Analysis). Our framework possesses several advantages compared with image-based approaches. First, it presents comparable landmarking accuracy, despite relying on a single, random reference specimen and much sparser sampling of the structure’s surface. Second, it is performant such that it can be efficiently run on consumer-grade personal computers. Finally, it is general and can be applied to any biological structure of interest, regardless of whether anatomical atlases are available.Our validation procedures indicate that the method is capable of recovering multivariate patterns of morphological variation that are largely indistinguishable from those obtained by manual digitization, indicating that the use of an automated landmarking approach should not result in different conclusions regarding the nature of multivariate patterns of morphological variation.The proposed point cloud-based approach has the potential to increase the scale and reproducibility of morphometrics research. To allow ALPACA to be used out-of-the-box by users with no prior programming experience, we implemented it as a module as part of the SlicerMorph project. SlicerMorph is an extension that enables geometric morphometrics data collection and 3D specimen analysis within the open-source 3D Slicer biomedical visualization ecosystem. We expect that convenient access to this platform will make ALPACA broadly applicable within ecology and evolution.
Single-cell analysis of prostaglandin E2-induced decidual cell differentiation: does extracellular 8-Br-cAMP cause artifacts?
Authors: Stadtmauer Daniel J. , Wagner Günter P. 
Published: September 2020

AbstractDevelopment of the uterine decidua, the transient maternal tissue contacting the fetus during extended gestation, is the hallmark of reproduction in many placental mammals. Differentiation of decidual stromal cells is known to be induced by stimuli that activate the nuclear progesterone receptor and the cyclic AMP/protein kinase A (cAMP/PKA) pathways. The nature of the stimulus upstream of PKA has not been clearly defined, although a number of candidates have been proposed. To bypass this uncertainty for in vitro experiments, direct addition of membrane-permeable cAMP along with progestin has been the prevailing method. Phylogenetic inference suggests that the inflammatory eicosanoid prostaglandin E2 (PGE2) was the stimulus that ancestrally induced decidualization. Accordingly, we developed a protocol to decidualize human endometrial stromal fibroblasts using progestin and PGE2 and analyzed the response in comparison with a cAMP-based protocol. Transcriptomic comparison reveals a common activation of core decidual cell genes between both treatments, and a set of senescence-related genes exaggerated under cAMP treatment. Single-cell transcriptomic analysis of PGE2-mediated decidualization revealed a major transcriptomic transition between an early activated cell state and a differentiated decidual state, but notably did not identify a developmental trajectory representing a distinct senescent decidual state as reported in recent literature. Furthermore, investigation of the signal transduction process underlying PGE2-mediated decidualization showed that it depends upon progestin-dependent induction of PGE2 receptor 2 (PTGER2 aka EP2) and PKA, the kinase activated by PTGER2. This progesterone-dependent induction of PTGER2 is absent in the opossum, a species incapable of decidualization. Together, these findings suggest that the origin of the decidual cell type involved the evolution of progesterone-dependent activation of the PGE2/EP2/PKA axis. We propose the use of PGE2 for in vitro decidualization studies as a potentially more physiological model than 8-Br-cAMP.