bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antarctic Climate History and Global Climate Changes
Authors: Lurcock Pontus , Florindo Fabio 
Published: January 2018

Abstract
Antarctic climate changes have been reconstructed from ice and sediment cores and numerical models (which also predict future changes). Major ice sheets first appeared 34 million years ago (Ma) and fluctuated throughout the Oligocene, with an overall cooling trend. Ice volume more than doubled at the Oligocene-Miocene boundary. Fluctuating Miocene temperatures peaked at 17–14 Ma, followed by dramatic cooling. Cooling continued through the Pliocene and Pleistocene, with another major glacial expansion at 3–2 Ma. Several interacting drivers control Antarctic climate. On timescales of 10,000–100,000 years, insolation varies with orbital cycles, causing periodic climate variations. Opening of Southern Ocean gateways produced a circumpolar current that thermally isolated Antarctica. Declining atmospheric CO2 triggered Cenozoic glaciation. Antarctic glaciations affect global climate by lowering sea level, intensifying atmospheric circulation, and increasing planetary albedo. Ice sheets interact with ocean water, forming water masses that play a key role in global ocean circulation.
Patterns of Disrespectful Physician Behavior at an Academic Medical Center: Implications for Training, Prevention, and Remediation
Authors: Hopkins Joseph , Hedlin Haley , Weinacker Ann , Desai Manisha 
Published: January 2018

Purpose
Physician disrespectful behavior affects quality of care, patient safety, and collaborative clinical team function. Evidence defining the demographics, ethnography, and epidemiology of disrespectful behavior is lacking.

Method
The authors conducted a retrospective analysis of reports of disrespectful physician behavior at Stanford Hospital and Clinics from March 2011 through February 2015. Events were stratified by role, gender, specialty, and location in the hospital or clinics where the event occurred. Event rate ratios were estimated using a multivariable negative binomial regression model. Correlation of rates of faculty and trainees in the same specialty was assessed.

Results
One hundred ninety-nine events concerned faculty; 160 concerned trainees. Events were concentrated among a small number of physicians in both groups. The rates of faculty and trainee events within the same specialty were highly correlated (Spearman’s rho: 0.90; P < .001). Male physicians had an adjusted event rate 1.86 (95% CI = 1.33–2.60; P < .001) times that of females. Procedural physicians were 3.67 times (95% CI = 2.63–5.13; P < .001) more likely to have a disrespectful behavior event than nonprocedural physicians when adjusting for other covariates. Most common location for faculty was the operating rooms (69 events, 34%); for trainees, the medical/surgical units (43 events, 27%).

Conclusions
Patterns of physician disrespectful behavior differed by role, gender, specialty, and location. Rates among faculty and trainees of the same specialty were highly correlated. These patterns can be used to create more focused education and training for specific physician groups and individualized remediation interventions.
Oligorecurrent Nodal Prostate Cancer
Authors: Tran Sebastien , Jorcano Sandra , Falco Teresa , Lamanna Giorgio , Miralbell Raymond , Zilli Thomas 
Published: January 2018

Objectives:
The objective of this study was to report long-term results of elective nodal radiotherapy (ENRT) in prostate cancer (PCa) patients with oligorecurrent nodal disease after primary treatment.

Methods:
Data of 53 oligorecurrent PCa patients (N1 and/or M1a) with ≤5 nodal metastases (n=108) treated with ENRT combined with androgen deprivation therapy (ADT) between 2004 and 2016 were retrospectively reviewed. Median prostate-specific antigen (PSA) and PSA doubling time (DT) were 3.4 ng/mL and 5 months, respectively. At restaging, 45% of the patients presented single nodal metastases, mainly located in the pelvis (n=38). All patients underwent ENRT between 45 and 50.4 Gy with a boost on positive nodes (median 64.4 Gy; 54 to 69 Gy) using mainly VMAT (n=24) or IMRT (n=21) techniques. Concomitant ADT was administered to all patients for a median time of 6 months.

Results:
After a median follow-up after ENRT of 44 months (range, 2 to 133), the 5-year biochemical disease-free and distant progression-free survival (DPFS) rates were 43% and 58%, respectively, with worse DPFS observed in patients with a PSA-doubling time <3 months (36.8% vs. 63.6%; P=0.029). Seventeen of 19 clinically relapsing patients presented lesions out of the ENRT field, and 10 were again oligometastatic. Only 2 patients presented with a CTCAE v3.0 grade ≥2 genitourinary toxicity.

Conclusions:
ENRT combined with short-course ADT is a safe and effective salvage modality for patients with oligorecurrent nodal PCa. Prospective randomized studies comparing focal SBRT versus ENRT are warranted to define the best treatment strategy.
Longitudinal resting-state functional magnetic resonance imaging in a mouse model of metastatic bone cancer reveals distinct functional reorganizations along a developing chronic pain state
Authors: Buehlmann David , Grandjean Joanes , Xandry Jael , Rudin Markus 
Published: January 2018

Abstract
Functional neuroimaging has emerged as attractive option for characterizing pain states complementing behavioral readouts or clinical assessment. In particular, resting-state functional magnetic resonance imaging (rs-fMRI) enables monitoring of functional adaptations across the brain, for example, in response to chronic nociceptive input. We have used rs-fMRI in a mouse model of chronic pain from breast cancer–derived tibial bone metastases to identify pain-induced alterations in functional connectivity. Combined assessment of behavioral readouts allowed for defining a trajectory as model function for extracting pain‐specific functional connectivity changes from the fMRI data reflective of a chronic pain state. Cingulate and prefrontal cortices as well as the ventral striatum were identified as predominantly affected regions, in line with findings from clinical and preclinical studies. Inhibition of the peripheral bone remodeling processes by antiosteolytic therapy led to a reduction of pain-induced network alterations, emphasizing the specificity of the functional readouts for a developing chronic pain state.
Role of GPCR (mu-opioid)–receptor tyrosine kinase (epidermal growth factor) crosstalk in opioid-induced hyperalgesic priming (type II)
Authors: Araldi Dionéia , Ferrari Luiz F. , Levine Jon D. 
Published: January 2018

Abstract
Repeated stimulation of mu-opioid receptors (MORs), by an MOR-selective agonist DAMGO induces type II priming, a form of nociceptor neuroplasticity, which has 2 components: opioid-induced hyperalgesia (OIH) and prolongation of prostaglandin-E2 (PGE2)-induced hyperalgesia. We report that intrathecal antisense knockdown of the MOR in nociceptors, prevented the induction of both components of type II priming. Type II priming was also eliminated by SSP-saporin, which destroys the peptidergic class of nociceptors. Because the epidermal growth factor receptor (EGFR) participates in MOR signaling, we tested its role in type II priming. The EGFR inhibitor, tyrphostin AG 1478, prevented the induction of prolonged PGE2-induced hyperalgesia, but not OIH, when tested out to 30 days after DAMGO. However, even when repeatedly injected, an EGFR agonist did not induce hyperalgesia or priming. A phosphopeptide, which blocks the interaction of Src, focal adhesion kinase (FAK), and EGFR, also prevented DAMGO-induced prolongation of PGE2 hyperalgesia, but only partially attenuated the induction of OIH. Inhibitors of Src and mitogen-activated protein kinase (MAPK) also only attenuated OIH. Inhibitors of matrix metalloproteinase, which cleaves EGF from membrane protein, markedly attenuated the expression, but did not prevent the induction, of prolongation of PGE2 hyperalgesia. Thus, although the induction of prolongation of PGE2-induced hyperalgesia at the peripheral terminal of peptidergic nociceptor is dependent on Src, FAK, EGFR, and MAPK signaling, Src, FAK, and MAPK signaling is only partially involved in the induction of OIH.
Percutaneous endoscopic gastrostomy with and without jejunal extension in patients with amyotrophic lateral sclerosis
Authors: Kirstein Martha M. , Körner Sonja , Schneider Andrea , Manns Michael P. , Petri Susanne , Voigtländer Torsten 
Published: January 2018

Background and aims
Amyotrophic lateral sclerosis (ALS) is a fatal degenerative disease of the motor nervous system, which is associated with severe loss of weight. Enteral nutrition through percutaneous endoscopic gastrostomy (PEG) or percutaneous endoscopic gastrostomy with jejunal extension (PEG-J) is generally recommended upon disease progression. There is no standard endoscopic method that should preferentially be performed. The aim of this study was to compare the number of adverse events, complication-free survival (CFS), and overall survival (OS) in patients who received PEG or PEG-J.

Patients and methods
All patients with ALS presenting for PEG or PEG-J placement to the Endoscopic Unit of Hannover Medical School, Germany, between 2009 and 2015 were retrospectively analyzed.

Results
Demographics were similar for patients receiving PEG (n=43) and PEG-J (n=39). The median intervention time and the absolute dose of propofol were significantly longer and, respectively, higher for patients with PEG-J (P=0.001 and 0.013). Intervention-related complications leading to hospitalization were significantly more frequent in patients who received PEG-J (36 vs. 4, P=0.001). The median CFS was significantly shorter in patients who received PEG-J compared with PEG (5 vs. 14 months, P=0.007). There was no difference in OS.

Conclusion
Intervention-related complications were more frequent and the median CFS was shorter in patients who received PEG-J, whereas there was no difference in OS. Given the poor prognosis of patients with ALS, our data provide first evidence that PEG might be the better tolerable option, with fewer complications. The decision on which nutritional system is implanted should be evaluated individually.
Low-Dose Epinephrine Boluses for Acute Hypotension in the PICU*
Authors: Reiter Pamela D. , Roth Jennifer , Wathen Beth , LaVelle Jaime , Ridall Leslie A. 
Published: January 2018

Objectives:
To describe the use of low-dose bolus epinephrine in critically ill children during an acute hypotensive episode or prearrest condition.

Design:
Institutional Review Board approved, single-center, retrospective medical chart review.

Setting:
Large medical-surgical PICU within a freestanding, tertiary care children’s hospital.

Patients:
Patients admitted to the PICU between June 1, 2015, and June 1, 2016, who received low-dose (≤ 5 µg/kg) IV bolus epinephrine.

Interventions:
None.

Measurement and Main Results:
Twenty-four resuscitation episodes (63 doses; 19 patients) were analyzed. Median age and weight of patients were 9 years (interquartile range, 1–15 yr) and 38.5 kg (interquartile range, 12–54.8 kg). Median Pediatric Risk of Mortality III score was 17 (interquartile range, 10–27). Mean epinephrine dose was 1.3 ± 1.1 µg/kg. Median number of doses per patient was two. If more than one dose was provided, median dosing interval was 6.5 minutes. Heart rate and mean arterial blood pressure were compared at the time of epinephrine administration and 1–4 minutes (median = 1 min) following administration. Heart rate changed from 130 ± 41 to 150 ± 33 beats/min (p < 0.05), and mean arterial blood pressure changed from 51 ± 17 to 75 ± 27 mm Hg (p < 0.001). Variability in mean arterial blood pressure response was observed; nonresponders required extracorporeal membrane oxygenation; 66% of doses resulted in up to 100% mean arterial blood pressure increase, and 21% of doses resulted in greater than 100% mean arterial blood pressure increase. Doses below 1 µg/kg were associated with a lower mean arterial blood pressure increase than doses between 1 and 5 µg/kg (mean percent change in mean arterial blood pressure = 6.6% vs 60%, respectively). Children less than or equal to 2 years old had the greatest percentage increase in heart rate and mean arterial blood pressure.

Conclusions:
Provision of low-dose bolus epinephrine during periods of acute hypotension can result in a significant increase in mean arterial blood pressure and heart rate. This dosing strategy may provide temporary stabilization while other therapies are added or adjusted, but further research is needed.
Supported self-management for cancer survivors to address long-term biopsychosocial consequences of cancer and treatment to optimize living well
Authors: Howell Doris D. 
Published: January 2018

Purpose of review
As individuals are living longer with cancer as a chronic disease, they face new health challenges that require the application of self-management behaviors and skills that may not be in their usual repertoire of self-regulatory health behaviors. Increasing attention is focused on supported self-management (SSM) programs to enable survivors in managing the long-term biopsychosocial consequences and health challenges of survivorship. This review explores current directions and evidence for SSM programs that enable survivors to manage these consequences and optimize health.

Recent findings
Cancer survivors face complex health challenges that affect daily functioning and well being. Multiple systematic reviews show that SSM programs have positive effects on health outcomes in typical chronic diseases. However, the efficacy of these approaches in cancer survivors are in their infancy; and the ‘one-size’ fits all approach for chronic disease self-management may not be adequate for cancer as a complex chronic illness. This review suggests that SSM has promising potential for improving health and well being of cancer survivors, but there is a need for standardizing SSM for future research.

Summary
Although there is increasing enthusiasm for SSM programs tailored to cancer survivors, there is a need for further research of their efficacy on long-term health outcomes.
The MoCA-Memory Index Score
Authors: Kaur Antarpreet , Edland Steven D. , Peavy Guerry M. 
Published: January 2018

Objective:
To compare ability of 2 measures of delayed memory (word list, story paragraph) to discriminate Normal Control (NC) subjects from those with amnestic mild cognitive impairment (aMCI).

Methods:
Demographic, neuropsychological, and diagnostic data contributed by 34 Alzheimer’s Disease Centers to the National Alzheimer’s Coordinating Center characterized 2717 individuals with a diagnosis of either NC (n=2205) or aMCI (n=512). The Montreal Cognitive Assessment-Memory Index Score (MoCA-MIS) assessed delayed word recall, and the Craft Story 21, delayed story recall. Logistic regression and receiver operator characteristic curves controlling for age, sex, and education assessed the ability of each test to differentiate NCs from subjects with aMCI.

Results:
The MoCA-MIS had significantly better sensitivity and specificity (area under the receiver operator characteristic curve 0.83 vs. 0.80, P=0.004). At sensitivity 80%, the specificity of the MoCA-MIS was 69.1%, compared with 62.8% for the Craft Story.

Conclusions:
These data suggest that the MoCA-MIS, a recall score from items within the MoCA, is better at discriminating NCs from subjects with aMCI than the Craft Story. Word recall may be an efficient alternative to paragraph recall for diagnostic screening within clinical practice and research settings.
HINTS in the Acute Vestibular Syndrome: Pearls and Pitfalls
Authors: Kung Nathan H. , Van Stavern Gregory P. , Gold Daniel R. 
Published: January 2018

Abstract:
The acute vestibular syndrome (AVS) is characterized by the rapid onset of vertigo, nausea/vomiting, nystagmus, unsteady gait, and head motion intolerance lasting more than 24 hours. We present 4 patients with AVS to illustrate the pearls and pitfalls of the Head Impulse, Nystagmus, Test of Skew (HINTS) examination.
Characterization ofP. falciparumdipeptidyl aminopeptidase 3 specificity reveals structural factors responsible for differences in amino acid preferences between peptide-based substrates and covalent inhibitors
Authors: de Vries Laura E. , Sanchez Mateo I. , Groborz Katarzyna , Kuppens Laurie , Poreba Marcin , Lehmann Christine , Yuan Fang , Arastu-Kapur Shirin , Horn Martin , Mares Michael , Bogyo Matthew , Drag Marcin , Deu Edgar 
Published: January 2018

AbstractMalarial dipeptidyl aminopeptidases (DPAPs) are cysteine proteases important for parasite development thus making them attractive drug targets. In order to develop inhibitors specific to the parasite enzymes it is necessary to map the determinants of substrate specificity of the parasite enzymes and its mammalian homologue cathepsin C (CatC). Here, we screened peptide-based libraries of substrates and covalent inhibitors to characterize the differences in specificity between parasite DPAPs and CatC, and used this information to develop highly selective DPAP1 and DPAP3 inhibitors. Interestingly, while the primary amino acid specificity of a protease is often used to develop potent inhibitors, we show that equally potent and highly specific inhibitors can be developed based on the sequences of non-optimal peptide substrates. Importantly, analysis of previously published data about the specificity of other proteases also unveiled significant discrepancies in the amino acid preference between substrates and inhibitors. In this article, we also discuss important structural and theoretical reasons that might account for these discrepancies. Overall, this study illustrates that focusing the development of protease inhibitors solely on substrate specificity might overlook important structural features that can be exploited to develop highly potent and selective compounds.
Inhibitors of lysosomal function or serum starvation in control or LAMP2 deficient cells do not modify the cellular levels of Parkinson disease-associated DJ-1/PARK 7 protein
Authors: Sánchez-Lanzas Raúl , Castaño José G. 
Published: January 2018

AbstractMutations in PARK7/DJ-1 gene are associated with familial autosomal recessive Parkinson disease. Recently, lysosomes and chaperone mediated autophagy (CMA) has been reported to participate in the degradation of DJ-1/PARK7 protein. Lamp-2A isoform is considered as the lysosomal receptor for the uptake of proteins being degraded by the CMA pathway. We have used several cell lines with disrupted LAMP2 gene expression and their respective control cells to test the possible role of lysosomal degradation and in particular CMA in DJ-1 /PARK7 degradation. Interruption of LAMP-2 expression did not result in an increase of the steady-state protein levels of DJ-1 /PARK7, as it would have been expected. Furthermore, no change in DJ-1 /PARK7 protein levels were observed upon inhibition of lysosomal function with NH4Cl or NH4Cl plus leupeptin, or after activation of CMA by serum starvation for 24h. Accordingly, we have not found any evidence that DJ-1 /PARK7 protein levels are regulated via lysosomal degradation or the CMA pathway.
Zebrafish type I collagen mutants faithfully recapitulate human type I collagenopathies
Authors: Gistelinck Charlotte , Kwon Ronald Y , Malfait Fransiska , Symoens Sofie , Harris Matthew P. , Henke Katrin , Fisher Shannon , Sips Patrick , Guillemyn Brecht , Bek Jan Willem , Vermassen Petra , De Saffel Hanna , Weis MaryAnn , De Paepe Anne , Eyre David R , Willaert Andy , Coucke Paul J 
Published: January 2018

ABSTRACTThe type I collagenopathies are a group of heterogeneous connective tissue disorders, that are caused by mutations in the genes encoding type I collagen and include specific forms of Osteogenesis Imperfecta (OI) and the Ehlers-Danlos syndrome (EDS). These disorders present with a broad disease spectrum and large clinical variability of which the underlying genetic basis is still poorly understood. In this study, we systematically analyzed skeletal phenotypes in a large set of zebrafish, with diverse mutations in the genes encoding type I collagen, representing different genetic forms of human OI, and the first zebrafish model of human EDS, which harbors characteristic defects in the soft connective tissues. Furthermore, we provide insight into how zebrafish and human type I collagen are compositionally and functionally related, which is relevant in the interpretation of human type I collagen related disease models. Our studies reveal a high degree of inter-genotype variability in phenotypic expressivity that closely correlates with associated OI severity. Further, we demonstrate the potential for select mutations to give rise to variable phenotypic penetrance, mirroring the clinical variability associated with human disease pathology. Therefore, our work suggests the potential for zebrafish to aid in identifying unknown genetic modifiers and mechanisms underlying the phenotypic variability in OI and related disorders. This will improve diagnostic strategies and enable the discovery of new targetable pathways for pharmacological interventionSIGNIFICANCE STATEMENTType I collagenopathies are a heterogenous group of connective tissue disorders, caused by genetic defects in type I collagen. Inherent to these disorders is a large clinical variability, of which the underlying molecular basis remains undefined. By systematically analyzing skeletal phenotypes in a large set of type I collagen zebrafish mutants we show that zebrafish models are able to both genocopy and phenocopy different forms of human type I collagenopathies, arguing for a similar pathogenetic basis. This study illustrates the potential of zebrafish as a tool to further dissect the molecular basis of phenotypic variability in human type I collagenopathies to improve diagnostic strategies as well as promote the discovery of new targetable pathways for pharmacological intervention of these disorders.
A computational method to aid the design and analysis of single cell RNA-seq experiments for cell type identification
Authors: Abrams Douglas , Kumar Parveen , Karuturi R. Krishna Murthy , George Joshy 
Published: January 2018

AbstractBackgroundThe advent of single cell RNA sequencing (scRNA-seq) enabled researchers to study transcriptomic activity within individual cells and identify inherent cell types in the sample. Although numerous computational tools have been developed to analyze single cell transcriptomes, there are no published studies and analytical packages available to guide experimental design and to devise suitable analysis procedure for cell type identification.ResultsWe have developed an empirical methodology to address this important gap in single cell experimental design and analysis into an easy-to-use tool called SCEED (Single Cell Empirical Experimental Design and analysis). With SCEED, user can choose a variety of combinations of tools for analysis, conduct performance analysis of analytical procedures and choose the best procedure, and estimate sample size (number of cells to be profiled) required for a given analytical procedure at varying levels of cell type rarity and other experimental parameters. Using SCEED, we examined 3 single cell algorithms using 48 simulated single cell datasets that were generated for varying number of cell types and their proportions, number of genes expressed per cell, number of marker genes and their fold change, and number of single cells successfully profiled in the experiment.ConclusionsBased on our study, we found that when marker genes are expressed at fold change of 4 or more than the rest of the genes, either Seurat or Simlr algorithm can be used to analyze single cell dataset for any number of single cells isolated (minimum 1000 single cells were tested). However, when marker genes are expected to be only up to fC 2 upregulated, choice of the single cell algorithm is dependent on the number of single cells isolated and proportion of rare cell type to be identified. In conclusion, our work allows the assessment of various single cell methods and also aids in examining the single cell experimental design.