bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thermoregulate, autoregulate and ventilate: brain-directed critical care for pediatric cardiac arrest
Authors: Kurz Jonathan E. , Smith Craig M. , Wainwright Mark S. 
Published: March 2017

Purpose of review
Cardiac arrest in childhood is associated with a high risk for mortality and poor long-term functional outcome. This review discusses the current evidence for neuroprotective therapies and goals for postarrest care in the context of the pathophysiology of hypoxic–ischemic injury, modalities for neurologic prognostication in these children and potential future monitoring paradigms for maximizing cerebral perfusion in the postarrest period.

Recent findings
The recent publication of the in-hospital and out-of-hospital Therapeutic Hypothermia After Cardiac Arrest trials demonstrated a lack of statistically significant benefit for the use of postarrest therapeutic hypothermia. As a result, targeted normothermic temperature management has become standard of care. Continuous electroencephalographic monitoring during the acute postarrest period provides useful additional data for neurologic prognostication, in addition to its value for detection of seizures. Ongoing research into noninvasive monitoring of cerebrovascular autoregulation has the potential to individualize blood pressure goals in the postarrest period, maximizing cerebral perfusion in these patients.

Summary
Therapeutic strategies after cardiac arrest seek to maximize cerebral perfusion while mitigating the effects of secondary brain injury and loss of autoregulation. Future research into new monitoring strategies and better long-term outcome measures may allow more precise targeting of therapies to these goals.
Nonoperative management of appendicitis in children
Authors: López Joseph J. , Deans Katherine J. , Minneci Peter C. 
Published: March 2017

Purpose of review
The aim of this review is to summarize the recent literature investigating nonoperative management of uncomplicated and complicated appendicitis and highlight recent data establishing its safety and efficacy.

Recent findings
Recent studies and clinical trials have demonstrated the efficacy of nonoperative treatment of both uncomplicated and complicated appendicitis, defined as perforated appendicitis with or without formed abscess or phlegmon. Nonoperative management of uncomplicated appendicitis has been reported to be effective in approximately 71–94% of cases. In complicated appendicitis, treatment with antibiotics alone or antibiotics with interval appendectomy has been shown to be a well tolerated and reasonable treatment alternative.

Summary
Appendicitis is one of the most common surgical diagnoses in children. The standard of care for many years has been surgical appendectomy; however, it carries with it risks including bleeding, wound complications, injury to surrounding structures, and the potential need for reoperation. Nonoperative management of both uncomplicated and complicated appendicitis in children is well tolerated and efficacious in select populations.
Early and Late Factors Impacting Patient and Graft Outcome in Pediatric Liver Transplantation
Authors: McLin Valérie A. , Allen Upton , Boyer Olivia , Bucuvalas John , Colledan Michele , Cuturi Maria‐Cristina , d'Antiga Lorenzo , Debray Dominique , Dezsofi Antal , de Goyet Jean de Ville , Dhawan Anil , Durmaz Ozlem , Falk Christine , Feng Sandy , Fischler Björn , Franchi‐Abella Stéphanie , Frauca Esteban , Ganschow Rainer , Gottschalk Stephen , Hadzic Nedim , Hierro Loreto , Horslen Simon , Hubscher Stefan , Karam Vincent , Kelly Deirdre , Maecker‐Kolhoff Britta , Mazariegos George , McKiernan Patrick , Melk Anette , Nobili Valerio , Ozgenç Funda , Reding Raymond , Sciveres Marco , Sharif Khalid , Socha Piotr , Toso Christian , Vajro Pietro , Verma Anita , Wildhaber Barbara E. , Baumann Ulrich 
Published: March 2017

ABSTRACTAs pediatric liver transplantation comes of age, experts gathered to discuss current paradigms and define gaps in knowledge warranting research to further improve patient and graft outcomes. Identified areas ripe for collaborative research include understanding the molecular and cellular mechanisms of tolerance and the role of donor‐specific antibodies, considering ways to expand donor pool, minimizing long‐term side effects of immunosuppression, and fine‐tuning surgical techniques to minimize biliary and vascular complications.
Reduced Bone Mineral Density in Children With Screening‐detected Celiac Disease
Authors: Björck Sara , Brundin Charlotte , Karlsson Magnus , Agardh Daniel 
Published: March 2017

ABSTRACTObjectives:The aim of the study was to assess whether bone mass and metabolism are impaired in genetically at‐risk children with screening‐detected celiac disease.Methods:Included were 71 children with screening‐detected celiac disease diagnosed at 10.0 ± 0.7 (mean ± standard deviation) years and 142 matched controls and 30 children with screening‐detected celiac disease diagnosed at 3.3 ± 0.4 years of age presently on a gluten‐free diet for 6.9 ± 1.1 years and 60 matched controls. All participants were assessed for bone mineral density (BMD) of total body and spine by dual x‐ray absorptiometry, serum 25(OH) vitamin D3, parathyroid hormone (PTH), interleukin (IL)‐1β, IL‐2, IL‐4, IL‐5, IL‐6, IL‐8, IL‐10, IL‐12p70, IL‐13, IL‐15, interferon gamma, and tumor necrosis factor alpha.Results:At diagnosis, screening‐detected celiac disease children as compared to controls had a mean −0.03 g/cm2 reduced BMD of both total body and spine (P = 0.009 and P = 0.005, respectively), a mean −11.4 nmol/L lower level of 25(OH) vitamin D3 (P < 0.001), and a mean +1.0 pmol/L higher PTH level (P < 0.001). Systemic levels of the cytokines IL‐1β, IL‐6, IL‐8, IL‐10, IL‐12p70, IL‐13, and tumor necrosis factor alpha were all increased in screening‐detected celiac disease as compared to controls (P < 0.001). No difference in BMD, 25(OH) vitamin D3, PTH, and cytokine levels were detected in children on a gluten‐free diet compared with controls.Conclusions:Children with screening‐detected celiac disease have reduced BMD, lower levels of vitamin D3, higher levels of PTH, and signs of systemic inflammation compared with controls. These differences were not found in celiac disease children on a gluten‐free diet, indicating that children with screening‐detected celiac disease benefit from an early diagnosis and treatment.
Effectiveness of Double‐balloon Enteroscopy‐facilitated Polypectomy in Pediatric Patients With Peutz‐Jeghers Syndrome
Authors: Belsha Dalia , Urs Arun , Attard Thomas , Thomson Mike 
Published: March 2017

ABSTRACTSizable small‐bowel (SB) polyps in Peutz‐Jeghers syndrome (PJS) pose a high risk for intussusception, often necessitating laparotomy and intraoperative enteroscopy. This series examines the effectiveness of double‐balloon enteroscopy (DBE) facilitated polypectomy for pediatric patients with PJS. Prospective analysis of collected data (6 years) on all patients with PJS referred for DBE‐facilitated SB polypectomy at a pediatric tertiary‐referral center. A total of 16 pediatric patients with PJS were referred for DBE‐facilitated SB polypectomy. Twenty‐two DBEs were performed. Large polyps (≥1 cm) were confirmed in 14 patients. Successful clearance of large SB polyps by DBE or laparoscopically assisted DBE (Lap‐DBE) was achieved in all patients. One patient experienced post‐Lap‐DBE pelvic abscess. All other patients remained asymptomatic and intervention free throughout follow‐up (median 26 months). This series demonstrates that DBE‐facilitated polypectomy is an effective therapeutic option in pediatric patients with PJS. It should be considered at an early age where possible.
Risk of Epilepsy in Individuals With Posttraumatic Stress Disorder: A Nationwide Longitudinal Study
Authors: Chen Yu-Hsiung , Wei Han-Ting , Bai Ya-Mei , Hsu Ju-Wei , Huang Kai-Lin , Su Tung-Ping , Li Cheng-Ta , Lin Wei-Chen , Wu Yi-Hui , Pan Tai-Long , Chen Tzeng-Ji , Tsai Shih-Jen , Chen Mu-Hong 
Published: March 2017

ABSTRACT

Objective
Several cross-sectional studies have reported a relationship between posttraumatic stress disorder (PTSD) and epilepsy. However, the temporal association between PTSD and epilepsy has rarely been investigated. We hypothesized that the risk of developing epilepsy later in life would be higher in patients with PTSD than in those without PTSD.

Methods
Using the Taiwan National Health Insurance Research Database, 6425 individuals with PTSD and 24,980 age-/sex-matched controls were enrolled between 2002 and 2009 in our study and followed up to the end of 2011. Those who developed epilepsy during the follow-up period were identified.

Results
Individuals with PTSD had a higher incidence of developing epilepsy (2.65 versus 0.33 per 1000 person-years, p < .001), with an earlier onset of epilepsy (37.53 years [15.80 years] versus 48.11 years [23.97 years], p = .002) than did the controls. Individuals with PTSD had an elevated risk of developing epilepsy (hazard ratio [HR] = 3.72, 95% confidence interval [CI] = 2.27–6.11) during the follow-up after adjustment for demographic data and medical and psychiatric comorbidities. Sensitivity analyses after excluding the observation in the first year (HR = 2.53, 95% CI = 1.44–4.47) and the first 3 years (HR = 2.14, 95% CI = 1.15–4.01) revealed consistent results.

Conclusions
These results supported a temporal association between PTSD and the development of epilepsy. Further studies are warranted to investigate the underlying pathophysiological pathways that explain the longitudinal association of PTSD with subsequent epilepsy.
Pain prevalence in cancer patients: status quo or opportunities for improvement?
Authors: Haumann Johan , Joosten E. (Bert) A. , Everdingen Marieke H.J. van den Beuken-van 
Published: March 2017

Purpose of review
Cancer incidence increases worldwide and thus more patients will suffer from cancer pain. As cancer pain severely affects quality of life, the decrease of pain should be of high priority for every clinician. In the last decade, attention for cancer pain and for its treatment has increased, and new pharmacological based treatment options became available. This gave reason to hypothesize a decrease in pain prevalence in cancer patients over the last decade.

Recent findings
Despite increased attention to cancer pain, pain prevalence in cancer patients has not significantly changed over the last decade as compared to the four decades before. This absence of change might be because of comorbidities cancer patients have, but also to undertreatment of pain, because of a lack of knowledge and pain measurement. Other factors underlying this absence of change are the use of incorrect coanalgesics in the case of treatment of neuropathic pain, as well as the present absence of potent analgesics with little side effects.

Summary
Consistent screening of pain in cancer patients and consequent correct treatment of pain might result in an impressive decrease in cancer pain. For further reduction of pain, new pharmacological analgesics need to be developed.
Ketamine for cancer pain: what is the evidence?
Authors: Jonkman Kelly , van de Donk Tine , Dahan Albert 
Published: March 2017

Purpose of review
In this review, we assess the benefit of ketamine in the treatment of terminal cancer pain that is refractory to opioid treatment and/or complicated by neuropathy.

Recent findings
While randomized controlled trials consistently show lack of clinical efficacy of ketamine in treating cancer pain, a large number of open-label studies and case series show benefit.

Summary
Ketamine is an N-methyl-d-aspartate receptor antagonist that at low-dose has effective analgesic properties. In cancer pain, ketamine is usually prescribed as adjuvant to opioid therapy when pain becomes opioid resistant or when neuropathic pain symptoms dominate the clinical picture. A literature search revealed four randomized controlled trials that examined the benefit of oral, subcutaneous or intravenous ketamine in opioid refractory cancer pain. None showed clinically relevant benefit in relieving pain or reducing opioid consumption. This suggests absence of evidence of benefit for ketamine as adjuvant analgesic in cancer pain. These findings contrast the benefit from ketamine observed in a large number of open-label studies and (retrospective) case series. We relate the opposite outcomes to methodological issues. The complete picture is such that there is still insufficient evidence to state with certainty that ketamine is not effective in cancer pain.
CNS syndromes associated with antibodies against metabotropic receptors
Authors: Lancaster Eric 
Published: March 2017

Purpose of review
Autoantibodies to Central nervous system (CNS) metabotropic receptors are associated with a growing family of autoimmune brain diseases, including encephalitis, basal ganglia encephalitis, Ophelia syndrome, and cerebellitis. The purpose of this review is to summarize the state of knowledge regarding the target receptors, the neurological autoimmune disorders, and the pathogenic mechanisms.

Recent findings
Antibodies to the γ-aminobutyric acid B receptor are associate with limbic encephalitis and severe seizures, often with small cell lung cancers. Metabotropic glutamate receptor 5 (mGluR5) antibodies associate with Ophelia syndrome, a relatively mild form of encephalitis linked to Hodgkin lymphoma. mGluR1 antibodies associate with a form of cerebellar degeneration, and also Hodgkin lymphoma. Antibodies to Homer 3, a protein associated with mGluR1, have also been reported in two patients with cerebellar syndromes. Dopamine-2 receptor antibodies have been reported by one group in children with basal ganglia encephalitis and other disorders.

Summary
CNS metabotropic receptor antibodies may exert direct inhibitory effects on their target receptors, but the evidence is more limited than with autoantibodies to ionotropic glutamate receptors. In the future, improved recognition of these patients may lead to better outcomes. Understanding the molecular mechanisms of the diseases may uncover novel treatment strategies.
Deconvolution of DNA methylation signatures identifies common differentially methylated gene regions on 1p36 across breast cancer subtypes
Authors: Titus Alexander J. , Way Gregory P. , Johnson Kevin C. , Christensen Brock C. 
Published: March 2017

ABSTRACTBreast cancer is a complex disease and studying DNA methylation (DNAm) in tumors is complicated by disease heterogeneity. We compared DNAm in breast tumors with normal-adjacent breast samples from The Cancer Genome Atlas (TCGA). We constructed models stratified by tumor stage and PAM50 molecular subtype and performed cell-type reference-free deconvolution on each model. We identified nineteen differentially methylated gene regions (DMGRs) in early stage tumors across eleven genes (AGRN, C1orf170, FAM41C, FLJ39609, HES4, ISG15, KLHL17, NOC2L, PLEKHN1, SAMD11, WASH5P). These regions were consistently differentially methylated in every subtype and all implicated genes are localized on chromosome 1p36.3. We also validated seventeen DMGRs in an independent data set. Identification and validation of shared DNAm alterations across tumor subtypes in early stage tumors advances our understanding of common biology underlying breast carcinogenesis and may contribute to biomarker development. We also provide evidence on the importance and potential function of 1p36 in cancer.
Transcription through the eye of a needle: daily and annual cycles of gene expression variation in Douglas-fir needles
Authors: Cronn Richard , Dolan Peter C. , Jogdeo Sanjuro , Wegrzyn Jill L. , Neale David B. , St. Clair J. Bradley , Denver Dee R. 
Published: March 2017

BackgroundPerennial growth in plants is the product of interdependent cycles of daily and annual stimuli that induce cycles of growth and dormancy. In conifers, needles are the key perennial organ that integrates daily and seasonal signals from light, temperature, and water availability. To understand the relationship between seasonal rhythms and seasonal gene expression responses in conifers, we examined diurnal and circannual needle mRNA accumulation in Douglas-fir (Pseudotsuga menziesii) needles at diurnal and circannual scales. Using mRNA sequencing, we sampled 6.1×109microreads from 19 trees and constructed ade novopan-transcriptome reference that includes 173,882 tree-derived transcripts. Using this reference, we mapped RNA-Seq reads from 179 samples that capture daily, seasonal, and annual variation.ResultsWe identified 12,042 diurnally-cyclic transcripts, 9,299 of which showed homology to annotated genes from other plant genomes, including angiosperm core clock genes. Annual analysis revealed 21,225 an-nually-cyclic transcripts, 17,335 of which showed homology to annotated genes from other plant genomes. The timing of maximum gene expression is associated with light quality at diurnal and photoperiod at annual scales, with two-thirds of transcripts reaching maximum expression +/− 2 hours from sunrise and sunset, and half reaching maximum expression +/− 20 days from winter and summer solstices. Comparison to published microarray-based gene expression studies in spruce (Picea) show that the rank order of expression for 760 putatively orthologous genes was significantly preserved, highlighting the generality of our findings.ConclusionsThis finding highlights the extensive annual and seasonal transcriptome variability demonstrated in conifer needles. At these temporal scales, 29% of expressed transcripts showed a significant diurnal rhythm, and 58.7% showed a significant circannual rhythm. Remarkably, thousands of genes reach their annual peak activity during winter dormancy, a time of metabolic stasis. Photoperiod appears to be a dominant driver of annual transcription patterns in Douglas-fir, and these results may be general for predicting rhythmic transcription patterns in emerging gymnosperm models.
Periaqueductal efferents to dopamine and GABA neurons of the VTA
Authors: Ntamati Niels R. , Creed Meaghan , Lüscher Christian 
Published: March 2017

AbstractNeurons in the periaqueductal gray (PAG) modulate threat responses and nociception. Activity in the ventral tegmental area (VTA) on the other hand can cause reinforcement and aversion. While in many situations these behaviors are related, the anatomical substrate of a crosstalk between the PAG and VTA remains poorly understood. Here we describe the anatomical and electrophysiological organization of the VTA-projecting PAG neurons. Using rabies-based, cell type-specific retrograde tracing, we observed that PAG to VTA projection neurons are evenly distributed along the rostro-caudal axis of the PAG, but concentrated in its posterior and ventrolateral segments. Optogenetic projection targeting demonstrated that the PAG-to-VTA pathway is predominantly excitatory and targets similar proportions ofIh-expressing VTA DA and GABA neurons. Taken together, these results set the framework for functional analysis of the interplay between PAG and VTA in the regulation of reward and aversion.
Cadherin Fat2 directs cellular mechanics to promote epithelial rotation
Authors: Viktorinová Ivana , Henry Ian , Tomancak Pavel 
Published: March 2017

AbstractLeft and right symmetry breaking is involved in many developmental processes that are important to form bodies and organs. One of them is the epithelial rotation of developing organs. However, how epithelial cells move, how they break symmetry to define common direction of their collective movement and what function rotational epithelial motions have in morphogenesis remain elusive. Here, we identified a dynamic actomyosin network with preferred retrograde contractility at the basal side of the rotating follicle epithelium inDrosophilaoogenesis. We provide evidence that unidirectional epithelial rotation is a result of actomyosin asymmetry cue transmission onto a tissue plane synchronized by the atypical cadherin Fat2, a key planar cell polarity regulator inDrosophilaoogenesis. We found that Fat2 directs actomyosin contractility to move the epithelial tissue in order to provide directed elongation of follicle cells. In contrast, loss of Fat2 results in anisotropic non-muscle Myosin II pulses that are disorganized in plane and deform cell shape, tissue andDrosophilaeggs. Our data indicate that directed elongation of follicle cells is critical for properDrosophilaegg morphogenesis. Together, we demonstrate the importance of atypical cadherins in the control of cell mechanics, left/right symmetry breaking and its propagation onto the tissue scale to facilitate proper organ morphogenesis. This process may be evolutionarily conserved in rotating animal organs.
Adult sex ratio bias in snowy plovers is driven by sex-specific early survival: implications for mating systems and population growth
Authors: Eberhart-Phillips Luke J. , Küpper Clemens , Miller Tom E. X. , Cruz-López Medardo , Maher Kathryn H. , dos Remedios Natalie , Stoffel Martin A. , Hoffman Joseph I. , Krüger Oliver , Székely Tamás 
Published: March 2017

ABSTRACTAdult sex ratio (ASR) is a central concept in population biology and a key factor in sexual selection, yet why do most demographic models ignore sex-biases? Vital rates often vary between the sexes and across life history, but their relative contributions to ASR variation remain poorly understood—an essential step to evaluate sex ratio theories in the wild and inform conservation. Here we combine structured two-sex population models with individual-based mark-recapture data from an intensively monitored polygamous population of snowy plovers. We show that a strongly male-biased ASR is primarily driven by sex-specific survival of juveniles, rather than adults or dependent offspring. This provides empirical support for theories of unbiased sex allocation when sex-differences in survival arise after the period of parental investment. Importantly, a conventional model ignoring sex-biases significantly overestimated population viability. We suggest that sex-specific population models are essential to understand the population dynamics of sexual organisms: reproduction and population growth is most sensitive to perturbations in survival of the limiting sex. Overall, our study suggests that sex-biased early survival may contribute towards mating system evolution and population persistence, with implications for both sexual selection theory and biodiversity conservation.SIGNIFICANCE STATEMENTSex biases are widespread in nature and represent a fundamental component of sexual selection and population biology—but at which point in life history do these biases emerge? Here we report a detailed individual-based demographic analysis of an intensively studied wild bird population to evaluate the origins of sex biases and their consequences on mating strategies and population dynamics. We document a strongly male-biased adult sex ratio, which is consistent with behavioral observations of female-biased polygamy. Notably, sex-biased juvenile, rather than adult survival, contributed most to the adult sex ratio. Sex-biases also strongly influenced population viability, which was significantly overestimated when sex ratio and mating system were ignored. Our study therefore has implications for both sexual selection theory and biodiversity conservation.