bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine-driven parameter screen of biochemical reactions
Authors: Poulain Stéphane , Arnaud Ophélie , Kato Sachi , Chen Iris , Ishida Hiro , Carninci Piero , Plessy Charles 
Published: January 2020

Abstract
The development of complex methods in molecular biology is a laborious, costly, iterative and often intuition-bound process where optima are sought in a multidimensional parameter space through step-by-step optimizations. The difficulty of miniaturizing reactions under the microliter volumes usually handled in multiwell plates by robots, plus the cost of the experiments, limit the number of parameters and the dynamic ranges that can be explored. Nevertheless, because of non-linearities of the response of biochemical systems to their reagent concentrations, broad dynamic ranges are necessary. Here we use a high-performance nanoliter handling platform and computer generation of liquid transfer programs to explore in quadruplicates 648 combinations of 4 parameters of a biochemical reaction, the reverse-transcription, which lead us to uncover non-linear responses, parameter interactions and novel mechanistic insights. With the increased availability of computer-driven laboratory platforms for biotechnology, our results demonstrate the feasibility and advantage of methods development based on reproducible, computer-aided exhaustive characterization of biochemical systems.
Neuroimaging of Intracerebral Hemorrhage
Authors: Rindler Rima S , Allen Jason W , Barrow Jack W , Pradilla Gustavo , Barrow Daniel L 
Published: January 2020

Abstract
Intracerebral hemorrhage (ICH) accounts for 10% to 20% of strokes worldwide and is associated with high morbidity and mortality rates. Neuroimaging is indispensable for rapid diagnosis of ICH and identification of the underlying etiology, thus facilitating triage and appropriate treatment of patients. The most common neuroimaging modalities include noncontrast computed tomography (CT), CT angiography (CTA), digital subtraction angiography, and magnetic resonance imaging (MRI). The strengths and disadvantages of each modality will be reviewed. Novel technologies such as dual-energy CT/CTA, rapid MRI techniques, near-infrared spectroscopy, and automated ICH detection hold promise for faster pre- and in-hospital ICH diagnosis that may impact patient management.
Soluble T-Cell Immunoglobulin Mucin Domain-3 Is Associated With Hepatitis C Virus Coinfection and Low-Grade Inflammation During Chronic Human Immunodeficiency Virus Infection
Authors: Hoel Hedda , Ueland Thor , Hove-Skovsgaard Malene , Hartling Hans Jakob , Gelpi Marco , Benfield Thomas , Ullum Henrik , Michelsen Annika E , Aukrust Pål , Nielsen Susanne Dam , Trøseid Marius 
Published: January 2020

Abstract

Background
In well treated human immunodeficiency virus infection (HIV), there is a residual immune activation and immune exhaustion that may contribute to increased risk of comorbidities. T-cell immunoglobulin mucin domain-3 (Tim-3) is an inhibitory molecule involved in HIV-associated T-cell dysfunction. The Tim-3 can be cleaved to soluble Tim-3 (sTim-3) that may serve as a soluble marker of immune exhaustion.

Methods
We measured sTim-3 with enzyme-linked immunosorbent assay DuoSets in a cross-sectional cohort of 1010 people with HIV (PWH) on antiretroviral therapy (ART), and 76 controls from the Copenhagen Co-Morbidity in HIV Infection (COCOMO) study, and in a longitudinal cohort of 60 PWH before and during ART.

Results
In the cross-sectional cohort, levels of sTim-3 were elevated in PWH on ART compared with controls, especially in hepatitis C virus (HCV)-coinfected individuals, and were associated with HCV viremia and inflammation. In the longitudinal cohort, pretreatment sTim-3 correlated with HIV viral load and decreased after ART initiation. Pretreatment sTim-3 correlated inversely with CD4 counts, but it did not predict immunological response in multivariable analyses.

Conclusions
Levels of sTim-3 decreased after ART initiation. In a cross-sectional cohort, levels of sTIM-3 were higher in PWH than in controls and were independently associated with HCV coinfection and high-sensitivity C-reactive protein, representing a potential link between immune exhaustion, inflammation, and risk of comorbidities.
First-In-Human Experience With Integration of Wireless Intracranial Pressure Monitoring Device Within a Customized Cranial Implant
Authors: Mitchell Kerry-Ann S , Anderson William , Shay Tamir , Huang Judy , Luciano Mark , Suarez Jose I , Manson Paul , Brem Henry , Gordon Chad R 
Published: January 2020

Abstract

BACKGROUND
Decompressive craniectomy is a lifesaving treatment for intractable intracranial hypertension. For patients who survive, a second surgery for cranial reconstruction (cranioplasty) is required. The effect of cranioplasty on intracranial pressure (ICP) is unknown.

OBJECTIVE
To integrate the recently Food and Drug Administration-approved, fully implantable, noninvasive ICP sensor within a customized cranial implant (CCI) for postoperative monitoring in patients at high risk for intracranial hypertension.

METHODS
A 16-yr-old female presented for cranioplasty 4-mo after decompressive hemicraniectomy for craniocerebral gunshot wound. Given the persistent transcranial herniation with concomitant subdural hygroma, there was concern for intracranial hypertension following cranioplasty. Thus, cranial reconstruction was performed utilizing a CCI with an integrated wireless ICP sensor, and noninvasive postoperative monitoring was performed.

RESULTS
Intermittent ICP measurements were obtained twice daily using a wireless, handheld monitor. The ICP ranged from 2 to 10 mmHg in the supine position and from −5 to 4 mmHg in the sitting position. Interestingly, an average of 7 mmHg difference was consistently noted between the sitting and supine measurements.

CONCLUSION
This first-in-human experience demonstrates several notable findings, including (1) newfound safety and efficacy of integrating a wireless ICP sensor within a CCI for perioperative neuromonitoring; (2) proven restoration of normal ICP postcranioplasty despite severe preoperative transcranial herniation; and (3) proven restoration of postural ICP adaptations following cranioplasty. To the best of our knowledge, this is the first case demonstrating these intriguing findings with the potential to fundamentally alter the paradigm of cranial reconstruction.
Chronic Care for Attention-Deficit/Hyperactivity Disorder: Clinical Management from Childhood Through Adolescence
Authors: Moss Cierra M. , Metzger Kristina B. , Carey Meghan E. , Blum Nathan J. , Curry Allison E. , Power Thomas J. 
Published: January 2020

ABSTRACT:

Objective:
Impairments generally persist when children diagnosed with attention-deficit/hyperactivity disorder (ADHD) mature into adolescence. To examine changes in ADHD care during the transition from childhood to adolescence, we conducted a retrospective, longitudinal cohort study of patients diagnosed with ADHD before the age of 10 years to assess changes from preadolescence through adolescence in (1) frequency by which primary care providers offer ADHD care to patients, (2) range of concerns assessed during patient encounters, and (3) treatments implemented or recommended.

Methods:
We identified patients from 3 practices included in a large primary care network who (1) were born between 1996 and 1997, (2) were diagnosed with ADHD before the age of 10 years, and (3) received primary care continuously from age 9 through late adolescence. Clinical care was compared among patients in preadolescence (age 9–11), early adolescence (age 12–14), and late adolescence (age 15–18).

Results:
Children diagnosed with ADHD before the age of 10 years were less likely to have a documented visit for ADHD during late adolescence (41% of patients) compared with preadolescence (63%, p < 0.001). Evidence of monitoring for depression, suicide, and substance abuse increased from preadolescence to adolescence (p < 0.001) and occurred in about 90% of adolescent patients. However, monitoring for risky sexual activity occurred in only about 50% of adolescents. Discussions of medication diversion and driver readiness were essentially not documented.

Conclusion:
The findings raise concerns about how primary care providers manage adolescents with a history of ADHD. Improving monitoring of risky sexual behavior and driver readiness and providing patient education about medication diversion are needed.
Automatic Detection of Target Engagement in Transcutaneous Cervical Vagal Nerve Stimulation for Traumatic Stress Triggers
Authors: Gurel Nil Z. , Wittbrodt Matthew T. , Jung Hewon , Ladd Stacy L. , Shah Amit J. , Vaccarino Viola , Bremner J. Douglas , Inan Omer T. 
Published: January 2020

AbstractTranscutaneous cervical vagal nerve stimulation (tcVNS) devices are attractive alternatives to surgical implants, and can be applied for a number of conditions in ambulatory settings, including stress-related neuropsychiatric disorders. Transferring tcVNS technologies to at-home settings brings challenges associated with the assessment of therapy response. The ability to accurately detect whether tcVNS has been effectively delivered in a remote setting such as the home has never been investigated. We designed and conducted a study in which 12 human subjects received active tcVNS and 14 received sham stimulation in tandem with traumatic stress, and measured continuous cardiopulmonary signals including the electrocardiogram (ECG), photoplethysmogram (PPG), seismocardiogram (SCG), and respiratory effort (RSP). We extracted physiological parameters related to autonomic nervous system activity, and created a feature set from these parameters to: 1) detect active (vs. sham) tcVNS stimulation presence with machine learning methods, and 2) determine which sensing modalities and features provide the most salient markers of tcVNS-based changes in physiological signals. Heart rate (ECG), vasomotor activity (PPG), and pulse arrival time (ECG+PPG) provided sufficient information to determine target engagement (compared to sham) in addition to other combinations of sensors. resulting in 96% accuracy, precision, and recall with a receiver operator characteristics area of 0.96. Two commonly utilized sensing modalities (ECG and PPG) that are suitable for home use can provide useful information on therapy response for tcVNS. The methods presented herein could be deployed in wearable devices to quantify adherence for at-home use of tcVNS technologies.
Microbial contributions to oxalate metabolism in health and disease
Authors: Liu Menghan , Devlin Joseph C. , Hu Jiyuan , Volkova Angelina , Battaglia Thomas W. , Byrd Allyson , Loke P’ng , Li Huilin , Ruggles Kelly V. , Tsirigos Aristotelis , Blaser Martin J. , Nazzal Lama 
Published: January 2020

AbstractOver-accumulation of oxalate in humans may lead to nephrolithiasis and nephrocalcinosis. Humans lack endogenous oxalate degradation pathways (ODP), but intestinal microbiota can degrade oxalate and protect against its absorption. However, the particular microbes that actively degrade oxalatein vivoare ill-defined, which restricts our ability to disentangle the underlying taxonomic contributions. Here we leverage large-scale multi-omics data (>3000 samples from >1000 subjects) to show that the human microbiota in health harbors diverse ODP-encoding microbial species, but an oxalate autotroph-Oxalobacter formigenes-dominates this function transcriptionally. Patients with Inflammatory Bowel Disease (IBD) are at significantly increased risk for disrupted oxalate homeostasis and calcium-oxalate nephrolithiasis. Here, by analyzing multi-omics data from the iHMP-IBD study, we demonstrate that the oxalate degradation function conferred by the intestinal microbiota is severely impaired in IBD patients. In parallel, the enteric oxalate levels of IBD patients are significantly elevated and associated with intestinal disease severity, which is consistent with the clinically known nephrolithiasis risk. The specific changes in ODP expression by several important taxa suggest that they play different roles in the IBD-induced nephrolithiasis risk.
Stratification of Behavioral Response to Transcranial Current Stimulation by Resting-State Electrophysiology
Authors: Mastakouri Atalanti A. 
Published: January 2020

AbstractTranscranial alternating current stimulation (tACS) enables the non-invasive stimulation of brain areas in desired frequencies, intensities and spatial configurations. These attributes have raised tACS to a widely used tool in cognitive neuroscience and a promising treatment in the field of motor rehabilitation. Nevertheless, considerable heterogeneity of its behavioral effects has been reported across individuals. We present a machine learning pipeline for predicting the behavioral response to 70 Hz contralateral motor cortex-tACS from Electroencephalographic resting-state activity preceding the stimulation. Specifically, we show in a cross-over study design that high-gamma (90–160 Hz) resting-state activity predicts arm-speed response to the stimulation in a concurrent reaching task. Moreover, we show in a prospective stimulation study that the behavioral effect size of stimulation significantly increases after the stratification of subjects with our prediction method. Finally, we discuss a plausible neurophysiological mechanism that links high resting-state gamma power in motor areas to stimulation response. As such, we provide a method that can distinguish responders from non-responders to tACS, prior to the stimulation treatment. This contribution could eventually bring us a step closer towards translating tACS into a safe and effective clinical treatment tool.
Loss of Ena/VASP interferes with lamellipodium architecture, motility and integrin-dependent adhesion
Authors: Damiano-Guercio Julia , Kurzawa Laëtitia , Mueller Jan , Dimchev Georgi , Nemethova Maria , Pokrant Thomas , Bruehmann Stefan , Linkner Joern , Blanchoin Laurent , Sixt Michael , Rottner Klemens , Faix Jan 
Published: January 2020

AbstractCell migration entails networks and bundles of actin filaments termed lamellipodia and microspikes or filopodia, respectively, as well as focal adhesions, all of which recruit Ena/VASP family members hitherto thought to antagonize efficient cell motility. However, we find these proteins to act as positive regulators of migration in different cell lines. CRISPR/Cas9-mediated loss of Ena/VASP proteins reduced lamellipodial actin assembly and perturbed lamellipodial architecture, as evidenced by changed network geometry as well as reduction of filament length and number that was accompanied by abnormal Arp2/3 complex and heterodimeric capping protein accumulation. Loss of Ena/VASP function also abolished the formation of microspikes normally embedded in lamellipodia, but not of filopodia capable of emanating without lamellipodia. Ena/VASP-deficiency also impaired integrin-mediated adhesion accompanied by reduced traction forces exerted through these structures. Our data thus uncover novel, cellular Ena/VASP functions of these actin polymerases that are fully consistent with their promotion of cell migration.
Improvement in Inner Retinal Function in Glaucoma with Nicotinamide (Vitamin B3) Supplementation: A Crossover Randomised Clinical Trial
Authors: Hui Flora , Tang Jessica , Williams Pete A , McGuinness Myra B , Hadoux Xavier , Casson Robert J , Coote Michael , Trounce Ian A , Martin Keith R. , van Wijngaarden Peter , Crowston Jonathan G 
Published: January 2020

AbstractImportanceRetinal ganglion cells endure significant metabolic stress in glaucoma but maintain capacity to recover function. Nicotinamide, a precursor of NAD+, is low in serum of glaucoma patients and its supplementation provides robust protection of retinal ganglion cells in preclinical models. However, the potential of nicotinamide in human glaucoma is unknown.BackgroundTo determine whether nicotinamide supplementation alongside conventional IOP-lowering therapy improves retinal ganglion cell function in glaucoma.DesignCrossover, double-masked, randomised clinical trial. Participants recruited from two tertiary care centres.ParticipantsFifty-seven participants, diagnosed and treated for primary glaucoma, enrolled.MethodsParticipants received oral placebo or nicotinamide and reviewed six-weekly. Participants commenced 6-weeks of 1.5 grams/day then 6 weeks of 3.0 grams/day followed by crossover without washout. Visual function measured using electroretinography and perimetry.Main outcome measuresChange in inner retinal function, determined by photopic negative response (PhNR) parameters: saturated PhNR amplitude (Vmax), ratio of PhNR/b-wave amplitude (Vmax ratio).ResultsPhNR Vmax improved beyond 95% coefficient of repeatability (COR) in 23% of participants following nicotinamide versus 9% on placebo. Overall, Vmax improved by 14.8% [95% CI: 2.8%, 26.9%], (p=0.02) on nicotinamide and 5.2% [−4.2%, 14.6%], (p=0.27) on placebo. Vmax ratio improved by 12.6% [5.0%, 20.2%], (p=0.002) following nicotinamide, 3.6% [−3.4%, 10.5%], (p=0.30) on placebo. A trend for improved visual field mean deviation was observed with 27% improving ≥1dB on nicotinamide and fewer deteriorating (4%) compared to placebo (p=0.02).ConclusionsNicotinamide supplementation can improve inner retinal function in glaucoma. Further studies underway to elucidate the effects of long-term nicotinamide supplementation.Trial RegistrationANZCTR trial ID: ACTRN12617000809336https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373001
Gene Expression Signature and Molecular Mechanism of Redox Homeostasis in Colorectal Cancer
Authors: Piran Mehran , Darayee Maryam , Piran Mehrdad , Sepahi Neda , Rahimi Amir 
Published: January 2020

AbstractCellular redox homeostasis is the important tool for normal cell function and survival. Oxidants, reductants and antioxidants are the players to maintain cellular homeostasis balance. However, in some conditions like cancer, the concentration and activation of these players are disturbed. This study walks you through the molecular mechanism of redox homeostasis to describe how expression level of these players would help colorectal cancer (CRC) cells continue proliferation and survive in the hypoxic environment of tumor. We proposed that O2-concentration is not detrimentally high in CRC cells since expression level of MnSOD didn’t change noticeably. We also suggested that High proliferative CRC cells obtain their energy by oxidation of H2S in or Electron transport chain (ETC) and keep the adequate concentration of H2S by diminishing the expression level of enzymes involved in sulfide oxidation pathway. Reduction in hydrogen sulfide oxidation results in a decrease in the level of GSH. Glutathione peroxidase enzyme requires GSH to convert H2O2into oxygen and water. Therefore, Level of hydrogen peroxide stays high which leads to an increase in cell proliferation. Furthermore, we analyzed the expression level of transcription factors sensitive to redox messengers.
Decoding the contents of consciousness from prefrontal ensembles
Authors: Kapoor Vishal , Dwarakanath Abhilash , Safavi Shervin , Werner Joachim , Besserve Michel , Panagiotaropoulos Theofanis I. , Logothetis Nikos K. 
Published: January 2020

ABSTRACTMultiple theories attribute to the primate prefrontal cortex a critical role in conscious perception. However, opposing views caution that prefrontal activity could reflect other cognitive variables during paradigms investigating consciousness, such as decision-making, monitoring and motor reports. To resolve this ongoing debate, we recorded from prefrontal ensembles of macaque monkeys during a no-report paradigm of binocular rivalry that instigates internally driven transitions in conscious perception. We could decode the contents of consciousness from prefrontal ensemble activity during binocular rivalry with an accuracy similar to when these stimuli were presented without competition. Oculomotor signals, used to infer conscious content, were not the only source of these representations since visual input could be significantly decoded when eye movements were suppressed. Our results suggest that the collective dynamics of prefrontal cortex populations reflect internally generated changes in the content of consciousness during multistable perception.One sentence summaryNeural correlates of conscious perception can be detected and perceptual contents can be reliably decoded from the spiking activity of prefrontal populations.
SynGAP splice isoforms differentially regulate synaptic plasticity and dendritic development
Authors: Araki Yoichi , Hong Ingie , Gamache Timothy R. , Ju Shaowen , Collado-Torres Leonardo , Shin Joo Heon , Huganir Richard L. 
Published: January 2020

SummarySynGAP is a synaptic Ras GTPase-activating protein (GAP) with four C-terminal splice variants: α1, α2, β, and γ. Although recent studies have implicatedSYNGAP1haploinsufficiency in ID/ASD pathogenesis, the degree to which each SynGAP isoform contributes to disease pathogenesis remains elusive. Here we demonstrate that individual SynGAP isoforms exhibit unique spatiotemporal expression and have distinct roles in neuronal and synaptic development. The SynGAP-α1 isoform, which undergoes robust liquid-liquid phase-separation with PSD-95 and is highly-enriched in synapses, is expressed late in development and disperses from synaptic spines in response to LTP-inducing synaptic activity to allow for AMPA receptor insertion and spine enlargement. In contrast, the SynGAP-β isoform, which undergoes less liquid-liquid phase-separation with PSD95 and is less synaptically targeted, is expressed early in development and promotes dendritic arborization. Interestingly, a SynGAP-α1 mutation that disrupts phase separation and synaptic targeting abolishes its function in plasticity and instead drives dendritic arbor development like the β isoform. These results demonstrate that distinct phase separation and synaptic targeting properties of SynGAP isoforms determine their function.HighlightsSynGAP-α1, α2, β, γ isoforms have distinct spatiotemporal expression and function in the brain.SynGAP-α1 is required for plasticity, while β is required for dendritic development.Liquid-liquid phase separation of SynGAP-α1 is required for its role in plasticity.SynGAP isoforms may differentially contribute to SYNGAP1 related human NDDs.
Integrated Analysis of Methylome and Transcriptome Following Developmental Atrazine Exposure in Zebrafish Reveals Aberrant Gene-Specific Methylation of Neuroendocrine and Reproductive Pathways
Authors: Bryan Chris , Lin Li , Xie Junkai , Ahkin Chin Tai Janiel , Horzmann Katharine A. , Wettschurack Kyle , Zhang Min , Freeman Jennifer , Yuan Chongli 
Published: January 2020

ABSTRACTAtrazine (ATZ) is one of the most commonly used herbicides in the United States. Previous studies have hypothesized the role of ATZ as an endocrine disruptor (EDC), and developmental exposure to ATZ has been shown to lead to behavioral and morphological alterations. Specific epigenetic mechanisms responsible for these alterations, however, are yet to be elucidated. In this study, we exposed zebrafish embryos to 0.3, 3, and 30 ppb (µg/L) of ATZ for 72 hours post fertilization. We performed whole-genome bisulfite sequencing (WGBS) to assess the effects of developmental ATZ exposure on DNA methylation in female fish brains. The number of differentially methylated genes (DMG) increase with increasing dose of treatments. DMGs are enriched in neurological pathways with extensive methylation changes consistently observed in neuroendocrine and reproductive pathways. To assess the effects of DNA methylation on gene expression, we integrated our data with transcriptomic data. Four genes, namely CHD9, FRAS1, PID1, and PCLO, were differentially expressed and methylated in each dose. Overall, this study identifies specific genes and pathways with aberrant methylation and expression following ATZ exposure as targets to elucidate the molecular mechanisms of ATZ toxicity and presents ATZ-induced site-specific DNA methylation as a potential mechanism driving aberrant gene expression.