bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurokinin-1 Receptor Deficiency Improves Survival in Murine Polymicrobial Sepsis Through Multiple Mechanisms in Aged Mice
Authors: Mella Juan R. , Stucchi Arthur F. , Duffy Elizabeth R. , Remick Daniel G. 
Published: August 2018

ABSTRACT

Objective:
Substance P (SP) is a neuropeptide that contributes to a proinflammatory state by binding to the neurokinin 1 receptor (NK-1R). Limiting this interaction has been shown to attenuate the acute inflammation. Our hypothesis was that NK-1R activation would contribute to the morbidity and mortality of sepsis in a model using mice genetically deficient in the NK-1R.

Methods:
To investigate the role of the SP/NK-1R axis in a murine model of sepsis, cecal ligation and puncture (CLP) in NK-1R deficient and wild type (WT) aged mice was performed. Acute inflammation was assessed by measuring circulating cytokines and clinical parameters.

Results:
Deletion of the NK-1R results in improved survival following CLP (NK-1R knockout mice survival = 100% vs. WT = 14%). A reduction in the inflammatory cytokines interleukin (IL) 6, macrophage inflammatory peptide 2, and IL-1 receptor antagonist, improved hemodynamic parameters, and increased neutrophilia were present in the NK-1R-deficient mice after CLP compared with WT mice.

Conclusions:
These data confirm the hypothesis that eliminating the SP/NK-1R interaction in a highly lethal murine model of sepsis leads to decreased morbidity and mortality through multiple mechanisms.
Pilot Study to Evaluate the Safety, Feasibility, and Financial Implications of a Postoperative Telemedicine Program
Authors: Nikolian Vahagn C. , Williams Aaron M. , Jacobs Benjamin N. , Kemp Michael T. , Wilson Jesse K. , Mulholland Michael W. , Alam Hasan B. 
Published: August 2018

Background:
Telemedicine in surgery holds promise for improving access and decreasing costs, but its role remains ill-defined. This pilot study was performed to investigate the safety, feasibility, and financial implications of providing postoperative care using an electronic clinic (eClinic) at a university hospital.

Methods:
An easy-to-use and secure eClinic platform was constructed in Epic (Epic Systems Corporation, Verona, WA). Patients undergoing laparoscopic cholecystectomy, appendectomy, and hernia repairs on an adult acute care surgery service were enrolled in this program over an 11-month period (March 2017 to January 2018). Patients with prolonged hospitalizations (greater than 4 nights), perioperative complications, drains, and open wounds were excluded. Demographics, clinical outcomes, encounter time, patient satisfaction survey results, and cost analysis were compared with the traditional clinic (tClinic) patient population.

Results:
Two hundred thirty-three eligible patients (61% female; mean age 41 ± 16 years) were enrolled in this program. Their demographics were no different than the tClinic. Frequencies of readmission, reoperation, and emergency department visits (2.7%, 0%, and 4.2%, respectively) in the eClinic group were also similar to the tClinic group. However, total visit time was significantly shorter in the eClinic group (14 vs 145 minutes, P < 0.01). Anonymous surveys demonstrated a high degree of satisfaction, with 85% of patients expressing desire to utilize the eClinic again. This program enhanced the capacity for new visits to tClinic, with a resultant projected increase in additional operative cases and revenue for the health care system.

Conclusions:
A safe and efficient postoperative telemedicine program can be constructed utilizing a widely available electronic medical record system, which can improve patient satisfaction, optimize throughput, and increase gross charges for the healthcare system.
Visual Snow: Visual Misperception
Authors: White Owen B. , Clough Meaghan , McKendrick Allison M. , Fielding Joanne 
Published: August 2018

Background:Visual snow (VS) is a constant visual disturbance described as flickering dots occupying the entire visual field. Recently, it was characterized as the defining feature of a VS syndrome (VSS), which includes palinopsia, photophobia, photopsias, entoptic phenomena, nyctalopia, and tinnitus. Sixty percent of patients with VSS also experience migraine, with or without aura. This entity often is considered psychogenic in nature, to the detriment of the patient's best interests, but the high frequency of similar visual symptoms argues for an organic deficit. The purpose of this review is to clarify VSS as a true entity and elaborate the nature of individual symptoms and their relationship to each other.Evidence Acquisition:The literature was reviewed with specific regard to the clinical presentation and psychophysical, neurophysiological, and functional imaging studies in patients with defined visual disturbances that comprise VSS.Results:Consideration of the individual symptoms suggests that multiple factors are potentially involved in the development of VSS, including subcortical network malfunction and cortical hyperexcitation. Although there is substantial overlap between VSS and migraine syndromes in terms of co-occurring symptoms, both neurophysiological and neuroimaging studies provide substantial evidence of separate abnormalities of processing, supporting these as separate syndromes.Conclusions:VSS is likely associated with either hyperactive visual cortices or, alternatively, impaired processing of simultaneous afferent information projecting to cortex. VSS likely results from widespread disturbance of sensory processing resulting in sensory misperception. There may be a number of syndromes associated with impaired sensory processing resulting in sensory misperception, including migraine, persistent perceptual postural dizziness, and tinnitus, which overlap with VSS. Elucidation of abnormality in one defined syndrome may provide a path forward for investigating all.
Effectiveness and Predictors of Response to 1-Hz Repetitive Transcranial Magnetic Stimulation in Patients With Obsessive-Compulsive Disorder
Authors: Singh Swarndeep , Kumar Saurabh , Gupta Ankit , Verma Rohit , Kumar Nand 
Published: August 2018

Objective
The present study aimed to assess the effectiveness of repetitive transcranial magnetic stimulation (rTMS) treatment targeting either supplementary motor area (SMA) or orbitofrontal cortex (OFC) among patients with OCD in real-world clinical practice settings. Also, the present study explored for potential predictors of response to rTMS treatment.

Methods
Retrospective review and analysis of records of 79 patients with medication-refractory OCD, all of whom had received 20 sessions of 1-Hz rTMS as part of routine clinical care. Of 79 patients, 46 received rTMS over the bilateral SMA and 33 over the left OFC. A reduction of 25% and 35% in Yale-Brown Obsessive Compulsive Scale (YBOCS) scores was used to classify outcome as partial and complete response, respectively. Statistical analysis was done using SPSS version 23.0.

Results
There was a significant decrease in mean YBOCS score from baseline to end of treatment (7.68 ± 5.62; t = 12.14, P < 0.001). Forty-five patients (57%) met criteria for partial response, of which 32 patients (40.5%) showed complete response. There was no significant difference in outcomes between patients receiving rTMS over SMA or OFC. Binary logistic regression analysis revealed presence of comorbid depression and higher baseline YBOCS score to be associated with lesser likelihood of response to rTMS.

Conclusions
This study provided evidence for overall effectiveness of adjunctive 1-Hz rTMS treatment over either SMA or OFC in patients with medication-refractory OCD, and reported comorbid depression and higher pretreatment YBOCS scores as potential predictors of poor response to rTMS.
Cognitive Effects of Transcranial Direct Current Stimulation in Healthy and Clinical Populations
Authors: Berryhill Marian E. , Martin Donel 
Published: August 2018

Abstract
Transcranial direct current stimulation (tDCS) is a neuromodulatory approach that is affordable, safe, and well tolerated. This review article summarizes the research and clinically relevant findings from meta-analyses and studies investigating the cognitive effects of tDCS in healthy and clinical populations. We recapitulate findings from recent studies where cognitive performance paired with tDCS was compared with performance under placebo (sham stimulation) in single sessions and longitudinal designs where cognitive effects were evaluated following repeated sessions. In summary, the tDCS literature currently indicates that the effects of tDCS on cognitive measures are less robust and less predictable compared with the more consistent effects on motor outcomes. There is also a notable difference in the consistency of single-session and longitudinal designs. In single-session tDCS designs, there are small effects amid high variability confounded by individual differences and potential sham stimulation effects. In contrast, longitudinal studies provide more consistent benefits in healthy and clinical populations, particularly when tDCS is paired with a concurrent task. Yet, these studies are few in number, thereby impeding design optimization. While there is good evidence that tDCS can modulate cognitive functioning and potentially produce longer-term benefits, a major challenge to widespread translation of tDCS is the absence of a complete mechanistic account for observed effects. Significant future work is needed to identify a priori responders from nonresponders for every cognitive task and tDCS protocol.
Transcranial Direct Current Stimulation in Obsessive-Compulsive Disorder, Posttraumatic Stress Disorder, and Anxiety Disorders
Authors: D'Urso Giordano , Mantovani Antonio , Patti Sara , Toscano Elena , de Bartolomeis Andrea 
Published: August 2018

Abstract
Obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), and anxiety disorders share the basic clinical feature of anxiety, which probably explains their common response to similar pharmacological and psychological interventions. Transcranial direct current stimulation (tDCS) is a neuromodulation technique that has proved effective in reducing the symptoms of a number of neuropsychiatric disorders. It was also used in healthy subjects to modulate neuropsychological processes that are involved in the pathophysiology of anxiety. We review the published studies in which tDCS was administered to patients with OCD, PTSD, or anxiety disorders. Our systematic search in the major electronic databases resulted in 14 articles for OCD, 1 for an OCD-related disorder (ie, hoarding disorder), 2 for PTSD, and 2 for anxiety disorders. In the studies involving OCD patients, tDCS was targeted to either the dorsolateral prefrontal cortex or the orbitofrontal cortex or the pre–supplementary motor area and induced a clear reduction of obsessive-compulsive symptoms. However, the lack of sham control groups and the great diversity in sample selection and tDCS protocols among studies prevent us from generalizing these results. In the studies involving PTSD and anxiety disorders patients, tDCS was applied over the dorsolateral prefrontal cortex and reduced symptoms, but the number of treated patients is too little to draw any conclusion on efficacy. However, these reports highlighted the importance of combining tDCS with different procedures, including computerized tasks and behavioral paradigms. In conclusion, even in its infancy, the use of tDCS for the treatment of OCD, PTSD, and anxiety disorders does show promise and deserves extensive research effort.
Proof of Kernel Work: a democratic low-energy consensus for distributed access-control protocols
Authors: Lundbæk Leif-Nissen , Janes Beutel Daniel , Huth Michael , Jackson Stephen , Kirk Laurence , Steiner Robert 
Published: August 2018

We adjust the Proof of Work (PoW) consensus mechanism used in Bitcoin and Ethereum so that we can build on its strength while also addressing, in part, some of its perceived weaknesses. Notably, our work is motivated by the high energy consumption for mining PoW, and we want to restrict the use of PoW to a configurable, expected size of nodes, as a function of the local blockchain state. The approach we develop for this rests on three pillars: (i)
Proof of Kernel Work
(PoKW), a means of dynamically reducing the set of nodes that can participate in the solving of PoW puzzles such that an adversary cannot increase his attack surface because of such a reduction; (ii)
Practical Adaptation of Existing Technology
, a realization of this PoW reduction through an adaptation of existing blockchain and enterprise technology stacks; and (iii)
Machine Learning for Adaptive System Resiliency
, the use of techniques from artificial intelligence to make our approach adaptive to system, network and attack dynamics. We develop here, in detail, the first pillar and illustrate the second pillar through a real use case, a pilot project done with Porsche on controlling permissions to vehicle and data log accesses. We also discuss pertinent attack vectors for PoKW consensus and their mitigation. Moreover, we sketch how our approach may lead to more democratic PoKW-based blockchain systems for public networks that may inherit the resilience of blockchains based on PoW.
In Vitro Expansion of Keratinocytes on Human Dermal Fibroblast-Derived Matrix Retains Their Stem-Like Characteristics
Authors: Wong Chee-Wai , Kinnear Beverley F. , Sobota Radoslaw M. , Ramalingam Rajkumar , LeGrand Catherine F. , Dye Danielle E. , Raghunath Michael , Lane E. Birgitte , Coombe Deirdre R. 
Published: August 2018

SummaryThe long-term expansion of keratinocytes under serum- and feeder free conditions generally results in diminished proliferation and an increased commitment to terminal differentiation. Here we present a serum and xenogeneic feeder free culture system that retains the self-renewal capacity of primary human keratinocytes.In vivo, the tissue microenvironment is a major contributor to determining cell fate and a key component of the microenvironment is the extracellular matrix (ECM). Accordingly, acellular ECMs derived from human dermal fibroblasts, cultured under macromolecular crowding conditions to facilitate matrix deposition and organisation, were used as the basis for a xenogeneic-free keratinocyte expansion protocol. A phospholipase A2decellularisation procedure produced matrices which, by proteomics analysis, resembled in composition the core matrix proteins of skin dermis. On these ECMs keratinocytes proliferated rapidly, retained their small size, expressed p63, did not express keratin 10 and rarely expressed keratin 16. Moreover, the colony forming efficiency of keratinocytes cultured on these acellular matrices was markedly enhanced. Collectively these data indicate that the dermal fibroblast-derived matrices support thein vitroexpansion of keratinocytes that maintained stem-like characteristics under serum free conditions.
Exploring the effect of microdosing psychedelics on creativity in an open-label natural setting
Authors: Prochazkova Luisa , Lippelt Dominique P. , Colzato Lorenza S. , Kuchar Martin , Sjoerds Zsuzsika , Hommel Bernhard 
Published: August 2018

AbstractIntroductionRecently popular sub-perceptual doses of psychedelic substances such as truffles, referred to as microdosing, allegedly have multiple beneficial effects including creativity and problem solving performance, potentially through targeting serotonergic 5-HT2Areceptors and promoting cognitive flexibility, crucial to creative thinking. Nevertheless, enhancing effects of microdosing remain anecdotal, and in the absence of quantitative research on microdosing psychedelics it is impossible to draw definitive conclusions on that matter. Here, our main aim was to quantitatively explore the cognitive-enhancing potential of microdosing psychedelics in healthy adults.MethodsDuring a microdosing event organized by the Dutch Psychedelic Society, we examined the effects of psychedelic truffles (which were later analyzed to quantify active psychedelic alkaloids) on two creativity-related problem-solving tasks: the Picture Concept Task assessing convergent thinking, and the Alternative Uses Task assessing divergent thinking. A short version of the Ravens Progressive Matrices task assessed potential changes in fluid intelligence. We tested once before taking a microdose and once while the effects were manifested.ResultsWe found that both convergent and divergent thinking performance was improved after a non-blinded microdose, whereas fluid intelligence was unaffected.ConclusionWhile this study provides quantitative support for the cognitive enhancing properties of microdosing psychedelics, future research has to confirm these preliminary findings in more rigorous placebo-controlled study designs. Based on these preliminary results we speculate that psychedelics might affect cognitive metacontrol policies by optimizing the balance between cognitive persistence and flexibility. We hope this study will motivate future microdosing studies with more controlled designs to test this hypothesis.
Pathway and network analysis of more than 2,500 whole cancer genomes
Authors: Reyna Matthew A. , Haan David , Paczkowska Marta , Verbeke Lieven P.C. , Vazquez Miguel , Kahraman Abdullah , Pulido-Tamayo Sergio , Barenboim Jonathan , Wadi Lina , Dhingra Priyanka , Shrestha Raunak , Getz Gad , Lawrence Michael S. , Pedersen Jakob Skou , Rubin Mark A. , Wheeler David A. , Brunak Søren , Izarzugaza Jose MG , Khurana Ekta , Marchal Kathleen , Mering Christian von , Sahinalp S. Cenk , Valencia Alfonso , Reimand Jüri , Stuart Joshua M. , Raphael Benjamin J. ,   on behalf of the PCAWG Drivers and Functional Interpretation Group and the ICGC/TCGA Pan-Cancer Analysis of Whole Genome Network
Published: August 2018

AbstractThe catalog of cancer driver mutations in protein-coding genes has greatly expanded in the past decade. However, non-coding cancer driver mutations are less well-characterized and only a handful of recurrent non-coding mutations, most notablyTERTpromoter mutations, have been reported. Motivated by the success of pathway and network analyses in prioritizing rare mutations in protein-coding genes, we performed multi-faceted pathway and network analyses of non-coding mutations across 2,583 whole cancer genomes from 27 tumor types compiled by the ICGC/TCGA PCAWG project. While few non-coding genomic elements were recurrently mutated in this cohort, we identified 93 genes harboring non-coding mutations that cluster into several modules of interacting proteins. Among these are promoter mutations associated with reduced mRNA expression inTP53, TLE4, andTCF4. We found that biological processes had variable proportions of coding and non-coding mutations, with chromatin remodeling and proliferation pathways altered primarily by coding mutations, while developmental pathways, including Wnt and Notch, altered by both coding and non-coding mutations. RNA splicing was primarily targeted by non-coding mutations in this cohort, with samples containing non-coding mutations exhibiting similar gene expression signatures as coding mutations in well-known RNA splicing factors. These analyses contribute a new repertoire of possible cancer genes and mechanisms that are altered by non-coding mutations and offer insights into additional cancer vulnerabilities that can be investigated for potential therapeutic treatments.
Mechanical heterogeneity and roles of parallel microtubule arrays in governing meiotic spindle length
Authors: Takagi Jun , Shimamoto Yuta 
Published: August 2018

AbstractMetaphase spindles are arrays of microtubules whose architecture provides the mechanism for regulated force generation required for proper segregation of chromosomes during cell division. Whereas long-standing models are based on continuous antiparallel microtubule arrays connecting two spindle poles and overlapping at the equator, spindles typically possess a more complex architecture with randomly arranged short filaments. How these heterogeneous multifilament arrays generate and respond to forces has been mysterious, as it has not been possible to directly measure and perturb spindle force while observing relevant filament motility. Here, we combined microneedle-based quantitative micromanipulation with high-resolution microtubule tracking of Xenopus egg extract spindles to simultaneously examine the force and individual filament motility in situ. We found that the microtubule arrays at the middle of the spindle half are considerably weak and fluid-like, being more adaptable to perturbing forces as compared to those near the pole and the equator. We also found that a force altering spindle length induces filament translocation nearer the spindle pole, where parallel microtubules predominate, while maintaining equatorial antiparallel filaments. Molecular perturbations suggested that the distinct mechanical heterogeneity of the spindle emerges from activities of kinesin-5 and dynein, two key spindle motor proteins. Together, our data establish a link between spindle architecture and mechanics, and highlight the importance of parallel microtubule arrays in maintaining its structural and functional stability.
Normalization of generalized transcript degradation improves accuracy in RNA-seq analysis
Authors: Xiong Bin , Yang Yiben , Fineis Frank R. , Wang Ji-Ping 
Published: August 2018

AbstractRNA-seq is a high-throughput assay to profile transcriptional activities in cells. Here we show that transcript degradation is gene-/sample-specific and presents a common and major source that may substantially bias the results in RNA-seq analysis. Most existing global normalization approaches are ineffective to correct for the degradation bias. We propose a novel pipeline named DegNorm (stands for degradation normalization) to adjust read counts for transcript degradation heterogeneity on a gene-by-gene basis while simultaneously controlling the sequencing depth. The robust and effective performance of this method is demonstrated in an extensive set of real RNA-seq data and simulated data.
Model neuron response statistics to natural images
Authors: Iyer Arvind , Burge Johannes 
Published: August 2018

AbstractTo model the responses of neurons in the early visual system, at least three basic components are required: a receptive field, a normalization term, and a specification of encoding noise. Here, we examine how the receptive field, the normalization factor, and the encoding noise impact the model neuron responses to natural images and the signal-to-noise ratio for natural image discrimination. We show that when these components are modeled appropriately, the model neuron responses to natural stimuli are Gaussian distributed, scale-invariant, and very nearly maximize the signal-to-noise ratio for stimulus discrimination. We discuss the statistical models of natural stimuli that can account for these response statistics, and we show how some commonly used modeling practices may distort these results. Finally, we show that normalization can equalize important properties of neural response across different stimulus types. Specifically, narrowband (stimulus- and feature-specific) normalization causes model neurons to yield Gaussian-distributed responses to natural stimuli, 1/f noise stimuli, and white noise stimuli. The current work makes recommendations for best practices and it lays a foundation, grounded in the response statistics to natural stimuli, upon which principled models of more complex visual tasks can be built.