bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk Factors for Vestibular and Oculomotor Outcomes After Sport-Related Concussion
Authors: Womble Melissa N. , McAllister-Deitrick Jamie , Marchetti Gregory F. , Reynolds Erin , Collins Michael W. , Elbin R.J. , Kontos Anthony P. 
Published: June 2019

Objective:
To investigate the association between risk factors and vestibular–oculomotor outcomes after sport-related concussion (SRC).

Study Design:
Cross-sectional study of patients seen 5.7 ± 5.4 days (range 0-30 days) after injury.

Setting:
Specialty clinic.

Participants:
Eighty-five athletes (50 male athletes and 35 female athletes) aged 14.1 ± 2.8 years (range 9-24 years) seeking clinical care for SRC.

Interventions:
Participants completed a clinical interview, history questionnaire, symptom inventory, and vestibular/ocularmotor screening (VOMS). Chi-square tests with odds ratios and diagnostic accuracy were used to examine the association between risk factors and VOMS outcomes.

Main Outcome Measures:
The VOMS.

Results:
Female sex (χ2 = 4.9, P = 0.03), on-field dizziness (χ2 = 7.1, P = 0.008), fogginess (χ2 = 10.3, P = 0.001), and post-traumatic migraine (PTM) symptoms including headache (χ2 = 16.7, P = 0.001), nausea (χ2 = 10.9, P = 0.001), light sensitivity (χ2 = 14.9, P = 0.001), and noise sensitivity (χ2 = 8.7, P = 0.003) were associated with presence of one or more postconcussion VOMS score above clinical cutoff. On-field dizziness (χ2 = 3.8, P = 0.05), fogginess (χ2 = 7.9, P = 0.005), and PTM-like symptoms including nausea (χ2 = 9.0, P = 0.003) and noise sensitivity (χ2 = 7.2, P = 0.007) were associated with obtaining a postconcussion near-point convergence (NPC) distance cutoff >5 cm. The likelihood ratios were 5.93 and 5.14 for VOMS symptoms and NPC distance, respectively.

Conclusions:
Female sex, on-field dizziness, fogginess, and PTM symptoms were predictive of experiencing vestibular–oculomotor symptoms/impairment after SRC.
Management of the protuberant premaxilla: where does it fit in?
Authors: Morris Lisa 
Published: June 2019

Purpose of review
To discuss multidisciplinary treatment options for the protuberant premaxilla associated with bilateral cleft lip and palate. Lessons have been learned throughout the years regarding the effect of growth restriction after early and aggressive therapy. Multiple surgical and orthodontic interventions are discussed. Recent literature will be highlighted and discussed.

Recent findings
A paucity of long-term studies was noted. Recent literature revealed numerous studies introducing innovative presurgical orthopedic devices as less expensive and easier to use alternatives to nasoalveolar molding. Multiple approaches to premaxillary setback were presented, offering multiple approaches to improve success rates and minimize burden to the patient. Novel orthodontic and advanced microvascular procedures were discussed as additional tools for treatment of the malpositioned premaxilla once skeletal maturity is reached.

Summary
Multidisciplinary team management of the protuberant premaxilla and bilateral cleft lip and palate is becoming increasingly embraced worldwide. Numerous surgical procedures and orthodontic treatments are required to optimally reposition the premaxilla; however, these interventions can inhibit growth, resulting in maxillary retrusion. Long-term follow-up studies are needed to determine what protocol is best. Studies should also include ways to overcome barriers to treatment success, such as late intervention, resource disparity, and limited access to care.
Kidney transplantation across minor ABO incompatibility: the use of A2 to B transplants
Authors: Gilbert Alexander J. 
Published: June 2019

Purpose of review
On 4 December 2014, the new kidney allocation system (KAS) went into effect. As part of this system, UNOS approved for the first time a national system with a specific mechanism affording priority to allocate kidneys across so-called ‘minor ABO incompatibility’ from blood group A2 donors into blood group B recipients. This significantly increased the number of such transplants done and the opportunities to learn about the specifics of such transplants.

Recent findings
A2 to B transplants have been demonstrated to be well tolerated, effective, and cost-effective ways of addressing disparities in the allocation system. Further data about the use of anti-A titers and the limits to successful transplant have better defined the bounds of who can benefit from such transplants.

Summary
The success thus far with A2 to B transplants should increase comfort and acceptance of the allocation policy changes and we should see further increases in centers willing to use such transplants to better address inequalities in the system.
Invasive Yersiniosis in a Pediatric Patient With β-Thalassemia Major: Acute Decompensation After Rapid Blood Transfusion
Authors: Hsu George , Jones Andrew , Thornton Ben 
Published: June 2019

Abstract

Yersinia enterocolitica infection, or yersiniosis, is a common cause of gastroenteritis in developing nations, but the disease is less common in the developed world. Yersiniosis typically presents as a self-limited gastroenteritis in an immunocompetent patient and rarely progresses to the more fulminant disseminated form. Certain patient populations are at greater risk of disseminated disease, and providers caring for these patients should have heightened suspicion for invasive disease. Patients dependent on serial transfusion therapy, such as those with inherited hemoglobinopathies, often have chronically elevated serum iron levels. These patients are at increased risk of fulminant yersiniosis due to the bacteria's siderophilic nature. Yersinia infection can be devastating in these patients, and early intervention with empiric antibiotics combined with targeted resuscitation can be essential in their care. The following case illustrates the utility for heightened surveillance, early intervention, and guided resuscitation in the management of this at-risk population.
Physical Therapy Scoliosis-Specific Exercises May Reduce Curve Progression in Mild Adolescent Idiopathic Scoliosis Curves
Authors: Zapata Karina A. , Sucato Daniel J. , Jo Chan-Hee 
Published: June 2019

Purpose:
To evaluate the curve magnitude in participants with mild adolescent idiopathic scoliosis (AIS) at high risk of progression who received outpatient physical therapy scoliosis-specific exercises (PSSEs).

Methods:
Participants with AIS curves 12° to 20° and Risser grade 0 chose either the PSSE or the control group. The PSSE group was instructed in the Barcelona Scoliosis Physical Therapy School. The control group was observed. Cobb angles were measured by one observer masked to group type at baseline, 6-month follow-up, and 1-year follow-up.

Results:
Forty-nine participants were enrolled (26 exercise vs 23 controls). Thirty-three participants (19 exercise vs 14 controls) were seen at 1-year follow-up. At 1-year follow-up, the exercise group had smaller curves than controls (16.3° vs 21.6°, P = .04) and less curve progression (0° vs 5.6°, P = .02). Bracing was performed similarly between groups at 1-year follow-up (37% vs 43%).

Conclusions:
In this small prospective series, PSSE resulted in significantly less curve progression compared with controls.
Apathy is Associated with Reduced Precision of Prior Beliefs about Action Outcomes
Authors: Hezemans Frank H. , Wolpe Noham , Rowe James B. 
Published: June 2019

ABSTRACTApathy is a debilitating syndrome that is associated with reduced goal-directed behaviour. Although apathy is common and detrimental to prognosis in many neuropsychiatric diseases, its underlying mechanisms remain controversial. We propose a new model of apathy, in the context of Bayesian theories of brain function, whereby actions require predictions of their outcomes to be held with sufficient precision for ‘explaining away’ differences in sensory inputs. In this active inference model, apathy would result from reduced precision of prior beliefs about action outcomes. Healthy adults (N=47) performed a visuomotor task that independently manipulated physical effort and reward, and served to estimate the precision of priors. Participants’ perception of their performance was biased towards the target, which was accounted for by precise prior beliefs about action outcomes. Crucially, prior precision was negatively associated with apathy. The results support a Bayesian account of apathy, that could inform future studies of clinical populations.
Gene expression-based identification of antigen-responsive CD8+ T cells on a single-cell level
Authors: Fuchs Yannick F. , Sharma Virag , Eugster Anne , Kraus Gloria , Morgenstern Robert , Dahl Andreas , Reinhardt Susanne , Petzold Andreas , Lindner Annett , Löbel Doreen , Bonifacio Ezio 
Published: June 2019

AbstractCD8+ T cells are important effectors of adaptive immunity against pathogens, tumors and self antigens. Here, we asked how human cognate antigen-responsive CD8+ T cells and their receptors could be identified in unselected single-cell gene expression data. Single-cell RNA sequencing and qPCR of dye-labelled antigen-specific cells identified large gene sets that were congruently up- or downregulated in virus-responsive CD8+ T cells under different antigen presentation conditions. Combined expression of TNFRSF9, XCL1, XCL2, and CRTAM was the most distinct marker of virus-responsive cells on a single-cell level. Using transcriptomic data, we developed a machine learning-based classifier that provides sensitive and specific detection of virus-responsive CD8+ T cells from unselected populations. Gene response profiles of CD8+ T cells specific for the autoantigen islet-specific glucose-6-phosphatase catalytic subunit-related protein differed markedly from virus-specific cells. These findings provide single-cell gene expression parameters for comprehensive identification of rare antigen-responsive cells and T cell receptors.One-sentence summaryIdentification of genes, gene sets, and development of a machine learning-based classifier that distinguishes antigen-responsive CD8+ T cells on a single-cell level.
Higher fitness yeast genotypes are less robust to deleterious mutations
Authors: Johnson Milo S. , Martsul Alena , Kryazhimskiy Sergey , Desai Michael M. 
Published: June 2019

AbstractNatural selection drives populations towards higher fitness, but second-order selection for adaptability and mutational robustness can also influence the dynamics of adaptation. In many microbial systems, diminishing returns epistasis contributes to a tendency for more-fit genotypes to be less adaptable, but no analogous patterns for robustness are known. To understand how robustness varies across genotypes, we measure the fitness effects of hundreds of individual insertion mutations in a panel of yeast strains. We find that more-fit strains are less robust: they have distributions of fitness effects (DFEs) with lower mean and higher variance. These shifts in the DFE arise because many mutations have more strongly deleterious effects in faster-growing strains. This negative correlation between fitness and robustness implies that second-order selection for robustness will tend to conflict with first-order selection for fitness.
Oncoprotein GT198 is a direct target of taxol
Authors: Yang Zheqiong , Gurvich Vadim J. , Gupta Mohan L. , Mivechi Nahid F. , Ko Lan 
Published: June 2019

ABSTRACTTaxol (paclitaxel) is one of the most successful chemotherapeutic drugs in the treatment of human cancer. It has recently been questioned whether the mechanism of action in mitotic arrest, which is ubiquitously present in all cells, is sufficient to explain the tumor specificity, clinical efficacy, and side effects of taxol. In this report, we have identified a new protein target of taxol as GT198 (gene symbolPSMC3IP, also known as Hop2). GT198 is an oncoprotein and a DNA repair factor involved in human common solid tumors. TheGT198gene carries germline mutations in breast and ovarian cancer families and recurrent somatic mutations in tumor microenvironment. Mutant GT198 was identified in pericyte stem cells on capillary blood vessels inducing tumor angiogenesis. GT198 is a DNA-binding protein dimer, also stimulates DNA repair, regulates meiosis, participates in homologous DNA recombination, and activates nuclear receptor-mediated gene expression. Here we show that taxol directly binds to the DNA-binding domain of GT198in vitro. Taxol serves as an allosteric inhibitor to block DNA binding to GT198 with an IC50 of 8.6 nM. Labeled taxol colocalizes with GT198 in interphase nuclei of cultured cells. Decreased GT198 expression desensitizes taxolinduced cell death, and taxol inhibits GT198 nuclear foci formation during DNA repair. Together, these results demonstrate that GT198 is a previously unrecognized direct protein target of taxol. The finding of taxol target as an oncoprotein GT198 in common solid tumors provides a rationale for the clinical efficacy of taxol. We anticipate that GT198 may serve as a clinical predictive marker of taxol efficacy as well as a new drug target for future anti-cancer therapy.
Stereoscopic Rendering in a Head Mounted Display Elicits Higher Functional Connectivity During Virtual Reality
Authors: Forlim Caroline Garcia , Bittner Lukas , Mostajeran Fariba , Steinicke Frank , Gallinat Jürgen , Kühn Simone 
Published: June 2019

AbstractVirtual reality (VR) simulates real world scenarios by creating a presence in users. Such immersive scenarios lead to more similar behaviour to that displayed in real world settings, which may facilitate the transfer of knowledge and skills acquired in VR to real world situations. VR has already been used in education, psychotherapy, rehabilitation and it is an appealing choice for training intervention. The aim was to investigate to what extend VR technology can be used in a magnetic resonance imaging scanner(MRI), addressing the question of whether brain connectivity differs between VR and screen via mirror projection presentations. Moreover, we investigate whether stereoscopic goggle stimulation, where eyes receive different input, would elicit more brain connectivity than stimulation where both eyes receive the same input (monoscopic). To our knowledge, there is no previous research addressing this question. Multiple analyses were performed to cover different aspects of brain connectivity: fractional low frequency fluctuation, independent component analysis, seed-based functional connectivity and graph analysis. In goggles (mono and stereoscopic) vs. screen, we found connectivity differences in cerebellum and postcentral gyrus and in visual and frontal inferior cortex in visual/default-mode networks. Considering specific areas, we found higher connectivity between superior frontal cortex and temporal lobe, as well as inferior parietal cortex with calcarine and lingual. Furthermore, superior frontal cortex and insula/putamen were more strongly connected in stereoscopic, in line with our hypothesis. We assume that conditions eliciting most connectivity should be suited for long-term interventions as extended training under these conditions could permanently improve functional/structural connectivity.
Firing rate homeostasis occurs in the absence of neuronal activity-regulated transcription
Authors: Tyssowski Kelsey M. , Letai Katherine C. , Rendall Samuel D. , Nizhnik Anastasia , Gray Jesse M. 
Published: June 2019

ABSTRACTDespite dynamic inputs, neuronal circuits maintain relatively stable firing rates over long periods. This maintenance of firing rate, or firing rate homeostasis, is likely mediated by homeostatic mechanisms such as synaptic scaling and regulation of intrinsic excitability. Because some of these homeostatic mechanisms depend on transcription of activity-regulated genes, including Arc and Homer1a, we hypothesized that activity-regulated transcription would be required for firing rate homeostasis. Surprisingly, however, we found that cultured mouse cortical neurons grown on multi-electrode arrays homeostatically adapt their firing rates to persistent pharmacological stimulation even when activity-regulated transcription is disrupted. Specifically, we observed firing rate homeostasis Arc knock-out neurons, as well as knock-out neurons lacking activity-regulated transcription factors, AP1 and SRF. Firing rate homeostasis also occurred normally during acute pharmacological blockade of transcription. Thus, firing rate homeostasis in response to increased neuronal activity can occur in the absence of neuronal-activity-regulated transcription.SIGNIFICANCE STATEMENTNeuronal circuits maintain relatively stable firing rates even in the face of dynamic circuit inputs. Understanding the molecular mechanisms that enable this firing rate homeostasis could potentially provide insight into neuronal diseases that present with an imbalance of excitation and inhibition. However, the molecular mechanisms underlying firing rate homeostasis are largely unknown.It has long been hypothesized that firing rate homeostasis relies upon neuronal activity-regulated transcription. For example, a 2012 review (PMID 22685679) proposed it, and a 2014 modeling approach established that transcription could theoretically both measure and control firing rate (PMID 24853940). Surprisingly, despite this prediction, we found that cortical neurons undergo firing rate homeostasis in the absence of activity-regulated transcription, indicating that firing rate homeostasis is controlled by non-transcriptional mechanisms.
NeuroPAL: A Neuronal Polychromatic Atlas of Landmarks for Whole-Brain Imaging inC. elegans
Authors: Yemini Eviatar , Lin Albert , Nejatbakhsh Amin , Varol Erdem , Sun Ruoxi , Mena Gonzalo E. , Samuel Aravinthan D.T. , Paninski Liam , Venkatachalam Vivek , Hobert Oliver 
Published: June 2019

ABSTRACTComprehensively resolving single neurons and their cellular identities from whole-brain fluorescent images is a major challenge. We achieve this inC. elegansthrough the engineering and use of a multicolor transgene called NeuroPAL (aNeuronalPolychromaticAtlas ofLandmarks). NeuroPAL worms share a stereotypical multicolor fluorescence map for the entire hermaphrodite nervous system that allows comprehensive determination of neuronal identities. Neurons labeled with NeuroPAL do not exhibit fluorescence in the green, cyan, or yellow emission channels, allowing the transgene to be used with numerous reporters of gene expression or neuronal dynamics. Here we showcase three studies that leverage NeuroPAL for nervous-system-wide neuronal identification. First, we determine the brainwide expression patterns of all metabotropic receptors for acetylcholine, GABA, and glutamate, completing a map of this communication network. Second, we uncover novel changes in cell fate caused by transcription factor mutations. Third, we record brainwide activity in response to attractive and repulsive chemosensory cues, characterizing multimodal coding and novel neuronal asymmetries for these stimuli. We present a software package that enables semi-automated determination of all neuronal identities based on color and positional information. The NeuroPAL framework and software provide a means to design landmark atlases for other tissues and organisms. In conclusion, we expect NeuroPAL to serve as an invaluable tool for gene expression analysis, neuronal fate studies, and for mapping whole-brain activity patterns.
CD44 inhibits α-SMA gene expression via a novel G-actin/MRTF mediated pathway that requires TGFβR/p38MAPK activity in murine skin fibroblasts
Authors: Wang Yan , Mack Judith A. , Maytin Edward V. 
Published: June 2019

ABSTRACTWell-regulated differentiation of fibroblasts into myofibroblasts (MF) is critical for skin wound healing. Neoexpression of α-smooth muscle actin (α-SMA), an established marker for MF differentiation, is driven by TGFβ receptor (TGFβR)-mediated signaling. Hyaluronan (HA) and its receptor CD44 may also participate in this process. To further understand this process, primary mouse skin fibroblasts were isolated and treatedin vitrowith recombinant TGF-β1 (rTGF-β1) to induce α-SMA expression. CD44 expression was also increased. Paradoxically, CD44 knockdown by RNA interference (RNAi) led to increased α-SMA expression and α-SMA-containing stress fibers. Removal of extracellular HA or inhibition of HA synthesis had no effect on α-SMA levels, suggesting a dispensable role for HA. Exploration of mechanisms linking CD44 knockdown to α-SMA induction, using RNAi and chemical inhibitors, revealed a requirement for non-canonical TGFβR signaling through p38MAPK. Decreased monomeric G-actin but increased filamentous F-actin following CD44 RNAi suggested a possible role for Myocardin-related Transcription Factor (MRTF), a known regulator of α-SMA transcription and itself being regulated by G-actin binding. CD44 RNAi promoted nuclear accumulation of MRTF and the binding to its transcriptional cofactor, SRF. MRTF knockdown abrogated the increased α-SMA expression caused by CD44 RNAi, suggesting that MRTF is required for CD44-mediated regulation of α-SMA. Finally, chemical inhibition of p38MAPK reversed nuclear MRTF accumulation after rTGF-β1 addition or CD44 RNAi, revealing a central requirement for p38MAPK in both cases. We concluded that CD44 regulates α-SMA gene expression through cooperation between two intersecting signaling pathways, one mediated by G-actin/MRTF and the other via TGFβR/p38MAPK.
Increased task-dependent functional connectivity by stimulation of the hippocampal network predicts memory enhancement
Authors: Warren Kristen N. , Hermiller Molly S. , Nilakantan Aneesha S. , Voss Joel L. 
Published: June 2019

AbstractSuccessful episodic memory involves dynamic increases in the coordination of activity across distributed hippocampal networks, including the posterior-medial network (PMN) and the anterior-temporal network (ATN). We tested whether this up-regulation of functional connectivity during memory processing can be enhanced within hippocampal networks by noninvasive stimulation, and whether such task-dependent connectivity enhancement predicts episodic memory improvement. Participants received stimulation targeting either the PMN or an out-of-network control location. We compared the effects of stimulation on fMRI connectivity measured during an autobiographical memory retrieval task versus during rest within the PMN and the ATN. PMN-targeted stimulation significantly increased connectivity during memory retrieval versus rest within the PMN. This effect was not observed in the ATN, or in either network due to control out-of-network stimulation. Task-dependent increases in connectivity due to PMN-targeted stimulation within the medial temporal lobe predicted improved performance of a separate episodic memory test. It is therefore possible to enhance the task-dependent regulation of hippocampal network connectivity that supports memory processing using noninvasive stimulation.
Enabling stable coexistence by modifying the environment
Authors: Pastor Alejandro , Nuño Juan Carlos , Olarrea José , de Vicente Javier 
Published: June 2019

AbstractIn this work coexistence is studied using a model based on two classical population models: the quasispecies of Eigen [1] and the daisyworld presented by Watson and Lovelock [2]. It is assumed that species are able to modify the environment. We show that this ability enables the coexistence between, at most, two species in equilibrium. Given an initial population, the problem arises as to determine which of the many equilibrium populations, i.e. extinction, only one species or coexistence of two species, will be reached as a function of the species characteristics, specifically their capacity to modify the environment and the optimal growth rate. These results are obtained under general assumptions, which broadens its applicability to other fields as evolutionary biology and social sciences.