bluuebunny/crossref_metadata_2025_split huggingface dataset:
Miniaturized Electromagnetic Device Abutment Improves Stability of the Dental Implants
Authors: Barak Shlomo , Matalon Shlomo , Dolkart Oleg , Zavan Barbara , Mortellaro Carmen , Piattelli Adriano 
Published: July 2018

Background:
The overall success and predictability of dental implant treatment hinge on the primary stability, direct bone-to implant contact formation, and quantity and/or quality of residual bone. Pulsed electromagnetic field has been reported to increase bone regeneration in various clinical situations. Therefore, it was hypothesized that devices which could locally generate a Pulsed electromagnetic field would stimulate bone healing and increase bone density surrounding implants.

Objective:
To retrospectively assess the effects of the miniaturized electromagnetic device (MED) on the implants stability for the first time in human subjects, in a prospective case controlled series.

Methods:
Twelve consecutive patients (28 implants) were included in the study.
Twelve MED healing caps and 16 regular control healing caps were inserted. Resonance frequency analysis (RFA) was performed at implant placement and abutment connection and an implant stability quotient value was given for each implant.

Results:
Twenty-eight dental implants were included in the current study. Maxillary implants stability was significantly higher with MED healing cups compared with controls at 15 days postimplantation (66.2 vs 62.1, P = .0008). Resonance frequency analysis test performed at 30 days postimplantation demonstrated significantly increased stability in MED as compared with the control 73.5 ± 3.2 vs 66.7 ± 4.8 in mandibular implants and 74 ± 1.7 vs 65 ± 2.3 in maxillary implants. At the 50 days postimplantation, RFA tests revealed markedly higher stability of the maxillary implants with MED active healing caps compared with nonactive 75.4 ± 5.1 vs 68.5 ± 8.5, respectively.

Conclusions:
We conclude that MED-abutment implants demonstrated a superior stability during the early phase of healing as compared with standard implants.
Machine learning without borders? An adaptable tool to optimize mortality prediction in diverse clinical settings
Authors: Christie S. Ariane , Hubbard Alan E. , Callcut Rachael A. , Hameed Morad , Dissak-Delon Fanny Nadia , Mekolo David , Saidou Arabo , Mefire Alain Chichom , Nsongoo Pierre , Dicker Rochelle A. , Cohen Mitchell Jay , Juillard Catherine 
Published: July 2018

BACKGROUND
Mortality prediction aids clinical decision making and is necessary for quality improvement initiatives. Validated metrics rely on prespecified variables and often require advanced diagnostics, which are unfeasible in resource-constrained contexts. We hypothesize that machine learning will generate superior mortality prediction in both high-income and low- and middle-income country cohorts.

METHODS
SuperLearner, an ensemble machine-learning algorithm, was applied to data from three prospective trauma cohorts: a highest-activation cohort in the United States, a high-volume center cohort in South Africa (SA), and a multicenter registry in Cameroon. Cross-validation was used to assess model discrimination of discharge mortality by site using receiver operating characteristic curves. SuperLearner discrimination was compared with standard scoring methods. Clinical variables driving SuperLearner prediction at each site were evaluated.

RESULTS
Data from 28,212 injured patients were used to generate prediction. Discharge mortality was 17%, 1.3%, and 1.7% among US, SA, and Cameroonian cohorts. SuperLearner delivered superior prediction of discharge mortality in the United States (area under the curve [AUC], 94–97%) and vastly superior prediction in Cameroon (AUC, 90–94%) compared with conventional scoring algorithms. It provided similar prediction to standard scores in the SA cohort (AUC, 90–95%). Context-specific variables (partial thromboplastin time in the United States and hospital distance in Cameroon) were prime drivers of predicted mortality in their respective cohorts, whereas severe brain injury predicted mortality across sites.

CONCLUSIONS
Machine learning provides excellent discrimination of injury mortality in diverse settings. Unlike traditional scores, data-adaptive methods are well suited to optimizing precise site-specific prediction regardless of diagnostic capabilities or data set inclusion allowing for individualized decision making and expanded access to quality improvement programming.

LEVEL OF EVIDENCE
Prognostic and therapeutic, level II and III.
Perceptual consciousness and cognitive access from the perspective of capacity-unlimited working memory
Authors: Gross Steven 
Published: July 2018

Theories of consciousness divide over whether perceptual consciousness is rich or sparse in specific representational content and whether it requires cognitive access. These two issues are often treated in tandem because of a shared assumption that the representational capacity of cognitive access is fairly limited. Recent research on working memory challenges this shared assumption. This paper argues that abandoning the assumption undermines post-cue–based ‘overflow’ arguments, according to which perceptual consciousness is rich and does not require cognitive access. Abandoning it also dissociates the rich/sparse debate from the access question. The paper then explores attempts to reformulate overflow theses in ways that do not require the assumption of limited capacity. Finally, it discusses the problem of relating seemingly non-probabilistic perceptual consciousness to the probabilistic representations posited by the models that challenge conceptions of cognitive access as capacity-limited.This article is part of the theme issue ‘Perceptual consciousness and cognitive access'.
Challenges for theories of consciousness: seeing or knowing, the missing ingredient and how to deal with panpsychism
Authors: Lamme Victor A. F. 
Published: July 2018

Significant progress has been made in the study of consciousness. Promising theories have been developed and a wealth of experimental data has been generated, both guiding us towards a better understanding of this complex phenomenon. However, new challenges have surfaced. Is visual consciousness about the seeing or the knowing that you see? Controversy about whether the conscious experience is better explained by theories that focus on phenomenal (P-consciousness) or cognitive aspects (A-consciousness) remains, and the debate seems to reach a stalemate. Can we ever resolve this? A further challenge is that many theories of consciousness seem to endorse high degrees of panpsychism—the notion that all beings or even lifeless objects have conscious experience. Should we accept this, or does it imply that these theories require further ingredients that would put a lower bound on beings or devices that have conscious experience? If so, what could these ‘missing ingredients’ be? These challenges are discussed, and potential solutions are offered.This article is part of the theme issue ‘Perceptual consciousness and cognitive access’.
The methodological puzzle of phenomenal consciousness
Authors: Phillips Ian 
Published: July 2018

Is phenomenal consciousness constitutively related to cognitive access? Despite being a fundamental issue for any science of consciousness, its empirical study faces a severe methodological puzzle. Recent years have seen numerous attempts to address this puzzle, either in practice, by offering evidence for a positive or negative answer, or in principle, by proposing a framework for eventual resolution. The present paper critically considers these endeavours, including partial-report, metacognitive and no-report paradigms, as well as the theoretical proposal that we can make progress by studying phenomenal consciousness as a natural kind. It is argued that the methodological puzzle remains obdurately with us and that, for now, we must adopt an attitude of humility towards the phenomenal.
This article is part of the theme issue ‘Perceptual consciousness and cognitive access’.
Partial report is the wrong paradigm
Authors: Stazicker James 
Published: July 2018

Is consciousness independent of the general-purpose information processes known as ‘cognitive access’? The dominant methodology for supporting this independence hypothesis appeals to partial report experiments as evidence for perceptual consciousness in the absence of cognitive access. Using a standard model of evidential support, and reviewing recent elaborations of the partial report paradigm, this article argues that the paradigm has the wrong structure to support the independence hypothesis. Like reports in general, a subject's partial report is evidence that she is conscious of information only where that information is cognitively accessed. So, partial report experiments could dissociate consciousness from cognitive access only if there were uncontroversial evidence for consciousness that did not imply reportability. There is no such evidence. An alternative, broadly Marrian methodology for supporting the independence hypothesis is suggested, and some challenges to it outlined. This methodology does not require experimental evidence for consciousness in the absence of cognitive access. Instead, it focuses on a function of perceptual consciousness when a stimulus is cognitively accessed. If the processes best suited to implement this function exclude cognitive access, the independence hypothesis will be supported. One relevant function of consciousness may be reflected in reason-based psychological explanations of a subject's behaviour.This article is part of the theme issue ‘Perceptual consciousness and cognitive access’.
Consciousness without report: insights from summary statistics and inattention ‘blindness’
Authors: Usher Marius , Bronfman Zohar Z. , Talmor Shiri , Jacobson Hilla , Eitam Baruch 
Published: July 2018

We contrast two theoretical positions on the relation between phenomenal and access consciousness. First, we discuss previous data supporting a mild Overflow position, according to which transient visual awareness can overflow report. These data are open to two interpretations: (i) observers transiently experience specific visual elements outside attentional focus without encoding them into working memory; (ii) no specific visual elements but only statistical summaries are experienced in such conditions. We present new data showing that under data-limited conditions observers cannot discriminate a simple relation (same versus different) without discriminating the elements themselves and, based on additional computational considerations, we argue that this supports the first interpretation: summary statistics (same/different) are grounded on the transient experience of elements. Second, we examine recent data from a variant of ‘inattention blindness’ and argue that contrary to widespread assumptions, it provides further support for Overflow by highlighting another factor, ‘task relevance’, which affects the ability to conceptualize and report (but not experience) visual elements.
This article is part of the theme issue ‘Perceptual consciousness and cognitive access’.
Adaptation of human iPSC-derived cardiomyocytes to tyrosine kinase inhibitors reduces acute cardiotoxicity via metabolic reprogramming
Authors: Wang Huan , Sheehan Robert P. , Palmer Adam C. , Everley Robert A. , Boswell Sarah A. , Ron-Harel Noga , Ringel Alison E. , Holton Kristina M. , Jacobson Connor A. , Erickson Alison R. , Maliszewski Laura , Haigis Marcia C. , Sorger Peter K. 
Published: July 2018

SUMMARYTyrosine kinase inhibitors (TKIs) are widely used to treat solid tumors but can be cardiotoxic. The molecular basis for this toxicity and its relationship to therapeutic mechanisms remain unclear; we therefore undertook a systems-level analysis of human cardiomyocytes exposed to four TKIs. Cardiomyocytes (CMs) differentiated from human induced pluripotent stem cells (hiPSCs) were exposed to sunitinib, sorafenib, lapatinib or erlotinib and responses assessed by functional assays, microscopy, RNA sequencing and mass spectrometry (GEO GSE114686; PRIDE PXD012043). TKIs have diverse effects on hiPSC-CMs distinct from inhibition of tyrosine-kinase mediated signal transduction; cardiac metabolism is particularly sensitive. Following Sorafenib treatment, oxidative phosphorylation is down-regulated, resulting in a profound defect in mitochondrial energetics. Cells adapt by upregulating aerobic glycolysis. Adaptation makes cells less acutely sensitive to Sorafenib, but may have long-term negative consequences. Thus, cardiomyocytes exhibit adaptive responses to anti-cancer drugs conceptually similar to those previously shown in tumors to mediate drug resistance.
Mice developing mammary tumors evolve T cell sequences shared with human breast cancer patients
Authors: Gordin Miri , Philip Hagit , Zilberberg Alona , Gidoni Moriah , Margalit Raanan , Clouser Christopher , Adams Kristofor , Vigneault Francois , Cohen Irun R. , Yaari Gur , Efroni Sol 
Published: July 2018

AbstractCancer immunotherapy by checkpoint blockade proves that an effective immune response to a tumor can be induced clinically. However, little is known about the evolution of tumor-associated T-cell receptor (TCR) repertoires without intervention. Here we studied TCR repertoire evolution in mice spontaneously developing mammary tumors; we sequenced peripheral blood alpha and beta TCRs of CD4+CD62L+CD44− T cells monthly for 8 months in 10 FVB/NJ mice transgenic at the Erbb2 locus, all developing tumors; 5 FVB/NJ mice without the transgene were age-matched controls. Sequences were either private (restricted to one mouse) or public (shared among mice); public sequences were either exclusive to the tumor group or inclusive among different groups. We now report that 1), public AA sequences were each encoded by many different nucleotide sequences (NT) recombinations (convergent recombination; CR); 2) mice developing tumors evolved tumor-exclusive public sequences, derived initially from private or from inclusive public sequences; and 3) tumor-exclusive public sequences in mice were also present among published public TCR sequences from human breast cancer patients. These cross-species tumor-exclusive TCR sequences manifested high CR; but the AA sequences shared by mice and humans did not share NT sequences. Thus, tumor-exclusive TCR AA sequences across species are selected from different NT recombination events. The roles of tumor-exclusive TCR repertoires in advancing or inhibiting tumor development and the effects of tumor immunotherapy on these T cells remain to be seen.
Splice junction centric approach to identify translated noncanonical isoforms in the human proteome
Authors: Lau Edward , Han Yu , Lam Maggie P. Y. 
Published: July 2018

AbstractRNA sequencing has led to the discovery of many transcript isoforms created by alternative splicing, but the translational status and functional significance of most alternative splicing events remain unknown. Here we applied a splice junction-centric approach to survey the landscape of protein alternative isoform expression in the human proteome. We focused on alternative splice events where pairs of splice junctions corresponding to included and excluded exons with appreciable read counts are translated together into selective protein sequence databases. Using this approach, we constructed tissue-specific FASTA databases from ENCODE RNA sequencing data, then reanalyzed splice junction peptides in existing mass spectrometry datasets across 10 human tissues (heart, lung, liver, pancreas, ovary, testis, colon, prostate, adrenal gland, and esophagus). Our analysis reidentified 1,108 non-canonical isoforms annotated in SwissProt. We further found 253 novel splice junction peptides in 212 genes that are not documented in the comprehensive Uniprot TrEMBL or Ensembl RefSeq databases. On a proteome scale, non-canonical isoforms differ from canonical sequences preferentially at sequences with heightened protein disorder, suggesting a functional consequence of alternative splicing on the proteome is the regulation of intrinsically disordered regions. We further observed examples where isoform-specific regions intersect with important cardiac protein phosphorylation sites. Our results reveal previously unidentified protein isoforms and may avail efforts to elucidate the functions of splicing events and expand the pool of observable biomarkers in profiling studies.Acronyms and AbbreviationsA3SSalternative 3-prime splice site;A5SSalternative 5-prime splice site;FDRfalse discovery rate;IDRintrinsically disordered regions;MXEmutually exclusive exons;PSIpercent spliced in;PTCpremature termination codon;PTMpost-translational modifications;SEskipped exon;RIretained intron.
Haplotype-phased common marmoset embryonic stem cells for genome editing using CRISPR/Cas9
Authors: Zhou Bo , Ho Steve S. , Leung Louis C. , Ward Thomas R. , Ho Marcus , Plastini Melanie J. , Vermilyea Scott C. , Emborg Marina E. , Golos Thaddeus G. , Albertelli Megan A. , Mourrain Philippe , Perrin Dimitri , Parker Karen J. , Urban Alexander E. 
Published: July 2018

ABSTRACTDue to anatomical and physiological similarities to humans, the common marmoset (Callithrix jacchus) is an ideal organism for the study human diseases. Researchers are currently leveraging genome-editing technologies such as CRISPR/Cas9 to genetically engineer marmosets for the in vivo biomedical modeling of human neuropsychiatric and neurodegenerative diseases. The genome characterization of these cell lines greatly reinforces these transgenic efforts. It also provides the genomic contexts required for the accurate interpretation of functional genomics data. We performed haplotype-resolved whole-genome characterization for marmoset ESC line cj367 from the Wisconsin National Primate Research Center. This is the first haplotype-resolved analysis of a marmoset genome and the first whole-genome characterization of any marmoset ESC line. We identified and phased single-nucleotide variants (SNVs) and Indels across the genome. By leveraging this haplotype information, we then compiled a list of cj367 ESC allele-specific CRISPR targeting sites. Furthermore, we demonstrated successful Cas9 Endonuclease Dead (dCas9) expression and targeted localization in cj367 as well as sustained pluripotency after dCas9 transfection by teratoma assay. Lastly, we show that these ESCs can be directly induced into functional neurons in a rapid, single-step process. Our study provides a valuable set of genomic resources for primate transgenics in this post-genome era.
Probing the limits of activity-silent non-conscious working memory
Authors: Trübutschek Darinka , Marti Sébastien , Ueberschär Henrik , Dehaene Stanislas 
Published: July 2018

SummaryTwo types of working memory (WM) have recently been proposed: conscious active WM, depending on sustained neural activity, and activity-silent WM, requiring neither conscious awareness nor accompanying neural activity. However, whether both states support identical forms of information processing is unknown. Theory predicts that activity-silent states are confined to passive storage and cannot operate on stored information. To determine whether an explicit reactivation is required prior to the manipulation of information in WM, we evaluated whether participants could mentally rotate brief visual stimuli of variable subjective visibility. Behaviorally, even for unseen targets, subjects reported the rotated location above chance after several seconds. As predicted, however, such blindsight performance was accompanied by neural signatures of conscious reactivation at the time of mental rotation, including a sustained desynchronization in alpha/beta frequency and a decodable representation of participants’ guess and response. Our findings challenge the concept of genuine non-conscious “working” memory, argue that activity-silent states merely support passive short-term memory, and provide a cautionary note for purely behavioral studies of non-conscious information processing.
Negative memory engrams in the hippocampus enhance the susceptibility to chronic social defeat stress
Authors: Zhang Tian Rui , Larosa Amanda , Di Raddo Marie-Eve , Wong Vanessa , Wong Alice S. , Wong Tak Pan 
Published: July 2018

AbstractThe hippocampus has been highly implicated in depression symptoms. Recent findings suggest that the expression and susceptibility of depression symptoms are related to the enhanced functioning of the hippocampus. We reasoned that hippocampal engrams, which represent ensembles of neurons with increased activity after memory formation, could underlie some contributions of the hippocampus to depression symptoms. Using the chronic social defeat stress (CSDS) model, we examined social defeat-related hippocampal engrams in mice that are either susceptible or resilient to the stressor. TetTag mice were used to label social defeat-related hippocampal ensembles by LacZ. Engram cells correspond to ensembles that were reactivated by the same stressor.Compared to resilient and non-stressed control mice, we found that in both the dorsal and ventral hippocampal CA1 regions, susceptible mice exhibited a higher reactivation of social defeat-related LacZ-labeled cells (i.e. engram cells). The density of CA1 engram cells correlated with the level of social avoidance. Using DREADD to reactivate social defeat-related but not neutral contextual stimuli-related CA1 engram cells decreased social interaction. Increased engram cells in susceptible mice were region specific and could not be found in the dentate gyrus. Susceptible mice exhibited more negative stimuli-, but not neutral stimuli-, related CA1 engram cells than resilient mice in the dorsal hippocampus. Finally, chronic, but not a short and subthreshold, social defeat protocol was necessary to increase CA1 engram cell density. Together, our findings reveal that the susceptibility to CSDS is regulated by hippocampal CA1 engrams for negative memory. Hippocampal engrams for negative memory may underlie the vulnerability and expression of cognitive symptoms in depression.Significance statementWe provided evidence that negative memory hippocampal engrams contribute to the susceptibility to developing depression-related behavior after chronic social defeat stress. The activation of positive memory engrams have been shown to alleviate depression-related behaviors, while our findings reveal the pathological roles of negative memory engrams that could lead to those behaviors. Increased negative memory engrams could be a downstream effect of the reported high hippocampal activity in animal models and patients with depression. Unlike affective symptoms, we know much less about the cellular mechanisms of the cognitive symptoms of depression. Given the crucial roles of hippocampal engrams in memory formation, enhanced reactivation of negative memory engrams could be an important cellular mechanism that underlies the cognitive symptoms of depression.