bluuebunny/crossref_metadata_2025_split huggingface dataset:
Atopic dermatitis in West Highland white terriers – part I: natural history of atopic dermatitis in the first three years of life
Authors: Favrot Claude , Fischer Nina , Olivry Thierry , Zwickl Lena , Audergon Sabrina , Rostaher Ana 
Published: October 2019

BackgroundCanine atopic dermatitis (cAD) is a common allergic skin disease that is known to affect individuals early in life; the natural history of its initial development has not been documented. Some breeds such as West Highland white terriers (WHWTs) are highly predisposed to cAD.ObjectivesTo follow 100 WHWT puppies during their first three years and to record the onset of clinical signs of cAD.AnimalsOne hundred and eight puppies from 29 litters were included and 90 were followed for three years.Methods and materialsPuppies were examined initially while with their breeders. After adoption, the owners were contacted twice each year and dogs were examined by veterinarians if signs compatible with cAD were detected; diagnosis of cAD was by two different definitions. The onset, location of the clinical signs and severity of cAD, as well as co‐morbidities were recorded.ResultsThe prevalence of cAD in the cohort was 52%. Most affected dogs (60%) developed signs of cAD during their first year of life and males were over‐represented. The location of clinical signs mirrored those of previous descriptions. The severity of cAD was mild in 36% and severe in 13% of affected WHWTs. Dogs with cAD often exhibited other atopic diseases, but only gastro‐intestinal signs were significantly different between WHWTs with and without cAD. Adverse reaction to foods was diagnosed in 24% of dogs.Conclusion and clinical importanceThis longitudinal study of puppies from a predisposed breed sheds new light on the early development of cAD in WHWTs.
Bilateral single-injection erector spinae plane block versus intrathecal morphine for postoperative analgesia in living donor laparoscopic hepatectomy: a randomized non-inferiority trial
Authors: Kang RyungA , Chin Ki Jinn , Gwak Mi Sook , Kim Gaab Soo , Choi Soo Joo , Kim Jong Man , Choi Gyu-Seong , Ko Justin Sangwook 
Published: October 2019

Background
Intrathecal morphine (ITM) provides effective postoperative analgesia in living donor hepatectomy but has significant adverse effects. Studies support the efficacy of erector spinae plane (ESP) blocks in laparoscopic abdominal surgery; we therefore hypothesized that they would provide non-inferior postoperative analgesia compared with ITM and reduce postoperative nausea/vomiting and pruritus. We conducted a randomized, controlled, non-inferiority trial to compare the analgesic efficacy of ITM and bilateral single-injection ESP blocks in laparoscopic donor hepatectomy.

Methods
Fifty-four donors were randomized to receive bilateral ESP blocks with 20 mL 0.5% ropivacaine (n=27) or 400 µg ITM (n=27). Primary outcome was resting pain score 24 hours postoperatively measured on an 11-point numeric rating scale. The prespecified non-inferiority limit was 1. Incidences of postoperative nausea/vomiting and pruritus were assessed.

Results
The mean treatment difference (ESP–ITM) in the primary outcome was 1.2 (95% CI 0.7 to 1.8). The 95% CI upper limit exceeded the non-inferiority limit. Opioid consumption and all other pain measurements were similar between groups up to 72 hours postoperatively. The ESP group had significantly lower incidences of postoperative vomiting (p=0.002) and pruritus (p<0.001).

Conclusions
Bilateral single-injection ESP blocks resulted in higher resting pain scores 24 hours postoperatively compared with ITM and thus did not meet the study definition of non-inferiority. However, the pain intensity with ESP blocks was mild (mean pain scores <3/10) and associated with reduced incidence of postoperative vomiting and pruritus. It warrants further investigation as an analgesic option after laparoscopic living donor hepatectomy.

Trial registration number
KCT0003191.
Red Ginseng Reduces Inflammatory Response via Suppression MAPK/P38 Signaling and p65 Nuclear Proteins Translocation in Rats and Raw 264.7 Macrophage
Authors: Adam Gareeballah Osman , Kim Gi-Beum , Lee Sei-Jin , Lee Heeryung , Kang Hyung-Sub , Kim Shang-Jin 
Published: October 2019

Lipopolysaccharides (LPS) cause systemic inflammatory responses, which are characterized by high mortality and multiple signs, including metabolic disturbances, respiratory acidosis, hypotension, and vital organs disorder. Cytokines secretion and oxidative stress are the main features of the disease. Diagnosis and treatment of systemic inflammation (SI) remain a challenge. Korean Red Ginseng (RG) is one of medicinal herbs that showed a potent anti-oxidant effect. We aimed to study the protective effects of RG on systemic inflammatory response in rats and RAW 264.7 macrophage cells induced by LPS. The rats were treated with water and alcohol extracts of RG for four weeks to prevent the inflammatory response. The result showed that LPS toxin increased morbidity and mortality, and induced liver, kidney, and lung injuries manifested by deteriorated biomarkers. Hypotension, hypomagnesemia, acidosis, and oxidative stress were observed in septic rats. However, RG extracts attenuated liver, kidney, and lung enzymes and metabolites in treated groups via its anti-inflammatory and anti-oxidant properties. Furthermore, RG improved magnesium and blood pressure in the treated groups. RAW 264.7 macrophage cells exposed to LPS disturbance in translocation of p65 and MAPK/p38. Nevertheless, RG-pretreated cells did not significantly alter. In conclusion, RG reduced the rates of mortality and morbidity of treated rats — liver, kidney, and lung injuries were protected in the treated groups through the potentiation of anti-oxidant defense. RG was able to conserve mitochondrial function, inhibiting the activation of MAPK/p38 signaling and suppressing NF-[Formula: see text]B p65 cytoplasm-nucleus transport. Further studies are needed to examine the effects on chronic conditions in animal models and human.
Mantle plumes and mantle dynamics in the Wilson cycle
Authors: Heron Philip J. 
Published: October 2019

Abstract
This review discusses the thermal evolution of the mantle following large-scale tectonic activities such as continental collision and continental rifting. About 300 myr ago, continental material amalgamated through the large-scale subduction of oceanic seafloor, marking the termination of one or more oceanic basins (e.g. Wilson cycles) and the formation of the supercontinent Pangaea. The present day location of the continents is due to the rifting apart of Pangaea, with the dispersal of the supercontinent being characterized by increased volcanic activity linked to the generation of deep mantle plumes. The discussion presented here investigates theories regarding the thermal evolution of the mantle (e.g. mantle temperatures and sub-continental plumes) following the formation of a supercontinent. Rifting, orogenesis and mass eruptions from large igneous provinces change the landscape of the lithosphere, whereas processes related to the initiation and termination of oceanic subduction have a profound impact on deep mantle reservoirs and thermal upwelling through the modification of mantle flow. Upwelling and downwelling in mantle convection are dynamically linked and can influence processes from the crust to the core, placing the Wilson cycle and the evolution of oceans at the forefront of our dynamic Earth.
Genioglossus muscle responses to resistive loads in severe OSA patients and healthy control subjects
Authors: Ruehland Warren R. , Rochford Peter D. , Pierce Robert J. , Trinder John , Jordan Amy S. , Cori Jennifer M. , O’Donoghue Fergal J. 
Published: October 2019

This study aimed to determine whether there is impairment of genioglossus neuromuscular responses to small negative pressure respiratory stimuli, close to the conscious detection threshold, in obstructive sleep apnea (OSA). We compared genioglossus electromyogram (EMGgg) responses to midinspiratory resistive loads of varying intensity (≈1.2–6.2 cmH2O·L−1·s), delivered via a nasal mask, between 16 severe OSA and 17 control participants while the subjects were awake and in a seated upright position. We examined the relationship between stimulus intensity and peak EMGgg amplitude in a 200-ms poststimulus window and hypothesized that OSA patients would have an increased activation threshold and reduced sensitivity in the relationship between EMGgg activation and stimulus intensity. There was no significant difference between control and OSA participants in the threshold ( P = 0.545) or the sensitivity ( P = 0.482) of the EMGgg amplitude vs. stimulus intensity relationship, where change in epiglottic pressure relative to background epiglottic pressure represented stimulus intensity. These results do not support the hypothesis that deficits in neuromuscular response to negative upper airway pressure exist in OSA during wakefulness; however, the results are likely influenced by a counterintuitive and novel genioglossus muscle suppression response observed in a significant proportion of both OSA and healthy control participants. This suppression response may relate to the inhibition seen in inspiratory muscles such as the diaphragm in response to sudden-onset negative pressure, and its presence provides new insight into the upper airway neuromuscular response to the collapsing force of negative pressure. NEW & NOTEWORTHY Our study used a novel midinspiratory resistive load stimulus to study upper airway neuromuscular responses to negative pressure during wakefulness in obstructive sleep apnea (OSA). Although no differences were found between OSA and healthy groups, the study uncovered a novel and unexpected suppression of neuromuscular activity in a large proportion of both OSA and healthy participants. The unusual response provides new insight into the upper airway neuromuscular response to the collapsing force of negative pressure.
The critical role of respiratory sinus arrhythmia on temporal cardiac dynamics
Authors: Yeh Chien-Hung , Juan Chung-Hau , Yeh Huei-Ming , Wang Cheng-Yen , Young Hsu-Wen Vincent , Lin Jiunn-Lee , Lin Chen , Lin Lian-Yu , Lo Men-Tzung 
Published: October 2019

Temporal cardiac properties provide alternative information in analyzing heart rate variability (HRV), which may be disregarded by the standard HRV analyses. Patients with congestive heart failure (CHF) are known to have distinct temporal features from the healthy individuals. However, the underlying mechanism leading to the variation remains unclear. Whether or not these parameters can finely classify the severity for CHF patients is uncertain as well. In this work, an electrocardiogram was monitored in advanced CHF patients using 24-h Holter in four conditions, including baseline, one and three months after atenolol therapy, and healthy individuals. Slope and area under the curve (AUC) of multiscale entropy (MSE) curve over short (scales 1–5) and long (scales 6–20) scales, and detrended fluctuation analysis (DFA) scaling exponents at short (4–11 beats) and intermediate (>11 beats) window sizes were calculated. The results show that short-time scale MSE-derived parameters (slope: −0.08 ± 0.10, −0.03 ± 0.10, 0.02 ± 0.06, 0.08 ± 0.06; AUC: 4.03 ± 2.11, 4.69 ± 1.28, 4.73 ± 0.94, and 6.17 ± 1.23) and short-time scale DFA exponent (0.79 ± 0.16, 0.95 ± 0.22, 1.11 ± 0.19, and 1.35 ± 0.20) can hierarchically classify all four conditions. More importantly, simulated R-R intervals with different fractions and amplitude of respiratory sinus arrhythmia (RSA) components were examined to validate our hypothesis regarding the essentiality of RSA in the improvement of cardiovascular function, and its tight association with unpredictability and fractal property of HRV, which is in line with our hypothesis that RSA contributes significantly to the generation of the unpredictability and fractal behavior of HR dynamics. NEW & NOTEWORTHY Temporal cardiac properties provide useful diagnostic parameters for patients with congestive heart failure (CHF). Our study hierarchically classified CHF patients with β-blocker treatment by using multiscale entropy and detrended fluctuation analysis. Also, we provided the evidence to validate the critical role of respiratory sinus arrhythmia in the fractal properties of heart rate variability.
Dissociating the effects of oxygen pressure and content on the control of breathing and acute hypoxic response
Authors: Dominelli Paolo B. , Baker Sarah E. , Wiggins Chad C. , Stewart Glenn M. , Sajgalik Pavol , Shepherd John R. A. , Roberts Shelly K. , Roy Tuhin K. , Curry Timothy B. , Hoyer James D. , Oliveira Jennifer L. , Foster Glen E. , Joyner Michael J. 
Published: October 2019

Arterial oxygen tension and oxyhemoglobin saturation ([Formula: see text]) decrease in parallel during hypoxia. Distinguishing between changes in oxygen tension and oxygen content as the relevant physiological stimulus for cardiorespiratory alterations remains challenging. To overcome this, we recruited nine individuals with hemoglobinopathy manifesting as high-affinity hemoglobin [HAH; partial pressure at 50% [Formula: see text] (P50) = 16 ± 0.4 mmHg] causing greater [Formula: see text] at a given oxygen partial pressure compared with control subjects ( n = 12, P50 = 26 ± 0.4 mmHg). We assessed ventilatory and cardiovascular responses to acute isocapnic hypoxia, iso-oxic hypercapnia, and 20 min of isocapnic hypoxia (arterial Po2 = 50 mmHg). Blood gas alterations were achieved with dynamic end-tidal forcing. When expressed as a function of the logarithm of oxygen partial pressure, ventilatory sensitivity to hypoxia was not different between groups. However, there was a significant difference when expressed as a function of [Formula: see text]. Conversely, the rise in heart rate was blunted in HAH subjects when expressed as a function of partial pressure but similar when expressed as a function of [Formula: see text]. Ventilatory sensitivity to hypercapnia was not different between groups. During sustained isocapnic hypoxia, the rise in minute ventilation was similar between groups; however, heart rate was significantly greater in the controls during 3 to 9 min of exposure. Our results support the notion that oxygen tension, not content, alters cellular Po2in the chemosensors and drives the hypoxic ventilatory response. Our study suggests that in addition to oxygen partial pressure, oxygen content may also influence the heart rate response to hypoxia.NEW & NOTEWORTHY We dissociated the effects of oxygen content and pressure of cardiorespiratory regulation studying individuals with high-affinity hemoglobin (HAH). During hypoxia, the ventilatory response, expressed as a function of oxygen tension, was similar between HAH variants and controls; however, the rise in heart rate was blunted in the variants. Our work supports the notion that the hypoxic ventilatory response is regulated by oxygen tension, whereas cardiovascular regulation may be influenced by arterial oxygen content and tension.
The Impact of Neighborhood Economic and Racial Inequalities on the Spatial Variation of Breast Cancer Survival in New Jersey
Authors: Wiese Daniel , Stroup Antoinette M. , Crosbie Amanda , Lynch Shannon M. , Henry Kevin A. 
Published: October 2019

AbstractBackground:Mapping breast cancer survival can help cancer control programs prioritize efforts with limited resources. We used Bayesian spatial models to identify whether breast cancer survival among patients in New Jersey (NJ) varies spatially after adjusting for key individual (age, stage at diagnosis, molecular subtype, race/ethnicity, marital status, and insurance) and neighborhood measures of poverty and economic inequality [index of concentration at the extremes (ICE)].Methods:Survival time was calculated for all NJ women diagnosed with invasive breast cancer between 2010 and 2014 and followed to December 31, 2015 (N = 27,078). Nonlinear geoadditive Bayesian models were used to estimate spatial variation in hazard rates and identify geographic areas of higher risk of death from breast cancer.Results:Significant geographic differences in breast cancer survival were found in NJ. The geographic variation of hazard rates statewide ranged from 0.71 to 1.42 after adjustment for age and stage, and were attenuated after adjustment for additional individual-level factors (0.87–1.15) and neighborhood measures, including poverty (0.9–1.11) and ICE (0.92–1.09). Neighborhood measures were independently associated with breast cancer survival, but we detected slightly stronger associations between breast cancer survival, and the ICE compared to poverty.Conclusions:The spatial models indicated breast cancer survival disparities are a result of combined individual-level and neighborhood socioeconomic factors. More research is needed to understand the moderating pathways in which neighborhood socioeconomic status influences breast cancer survival.Impact:More effective health interventions aimed at improving breast cancer survival could be developed if geographic variation were examined more routinely in the context of neighborhood socioeconomic inequalities in addition to individual characteristics.
Clonality, Antigen Recognition, and Suppression of CD8+ T Cells Differentially Affect Prognosis of Breast Cancer Subtypes
Authors: Hammerl Dora , Massink Maarten P.G. , Smid Marcel , van Deurzen Carolien H.M. , Meijers-Heijboer Hanne E.J. , Waisfisz Quinten , Debets Reno , Martens John W.M. 
Published: October 2019

AbstractPurpose:In breast cancer, response rates to immune therapies are generally low and differ significantly across molecular subtypes, urging a better understanding of immunogenicity and immune evasion.Experimental Design:We interrogated large gene-expression data sets including 867 node-negative, treatment-naïve breast cancer patients (microarray data) and 347 breast cancer patients (whole-genome sequencing and transcriptome data) according to parameters of T cells as well as immune microenvironment in relation to patient survival.Results:We developed a 109–immune gene signature that captures abundance of CD8 tumor-infiltrating lymphocytes (TIL) and is prognostic in basal-like, her2, and luminal B breast cancer, but not in luminal A or normal-like breast cancer. Basal-like and her2 are characterized by highest CD8 TIL abundance, highest T-cell clonality, highest frequencies of memory T cells, and highest antigenicity, yet only the former shows highest expression level of immune and metabolic checkpoints and highest frequency of myeloid suppressor cells. Also, luminal B shows a high antigenicity and T-cell clonality, yet a low abundance of CD8 TILs. In contrast, luminal A and normal-like both show a low antigenicity, and notably, a low and high abundance of CD8 TILs, respectively, which associates with T-cell influx parameters, such as expression of adhesion molecules.Conclusions:Collectively, our data argue that not only CD8 T-cell presence itself, but rather T-cell clonality, T-cell subset distribution, coinhibition, and antigen presentation reflect occurrence of a CD8 T-cell response in breast cancer subtypes, which have been aborted by distinct T-cell–suppressive mechanisms, providing a rationale for subtype-specific combination immune therapies.
FDA Approval Summary: Palbociclib for Male Patients with Metastatic Breast Cancer
Authors: Wedam Suparna , Fashoyin-Aje Lola , Bloomquist Erik , Tang Shenghui , Sridhara Rajeshwari , Goldberg Kirsten B. , Theoret Marc R. , Amiri-Kordestani Laleh , Pazdur Richard , Beaver Julia A. 
Published: October 2019

Abstract

On April 4, 2019, the FDA approved a supplemental new drug application for palbociclib (IBRANCE), to expand the approved indications in women with hormone receptor (HR)-positive, HER2-negative advanced or metastatic breast cancer (MBC) in combination with an aromatase inhibitor or fulvestrant, to include men. Palbociclib was first approved in 2015 for use in combination with letrozole for the treatment of estrogen receptor–positive, HER2-negative advanced breast cancer as initial endocrine-based therapy in postmenopausal women and subsequently in 2016 in combination with fulvestrant in women with HR-positive, HER2-negative advanced breast cancer with disease progression following endocrine therapy. The current approval was primarily based on the results of the PALOMA-2 and PALOMA-3 trials and, supported by real-world data from electronic health records and insurance claims. To support the safety evaluation in male patients, data from two phase I studies with palbociclib and safety information from the global safety database, were also reviewed. This article summarizes FDA decision-making and data supporting the approval of palbociclib for the treatment of male patients with HR-positive, HER2-negative advanced or MBC.
Atypical KRASG12R Mutant Is Impaired in PI3K Signaling and Macropinocytosis in Pancreatic Cancer
Authors: Hobbs G. Aaron , Baker Nicole M. , Miermont Anne M. , Thurman Ryan D. , Pierobon Mariaelena , Tran Timothy H. , Anderson Andrew O. , Waters Andrew M. , Diehl J. Nathaniel , Papke Bjoern , Hodge Richard G. , Klomp Jennifer E. , Goodwin Craig M. , DeLiberty Jonathan M. , Wang Junning , Ng Raymond W.S. , Gautam Prson , Bryant Kirsten L. , Esposito Dominic , Campbell Sharon L. , Petricoin Emanuel F. , Simanshu Dhirendra K. , Aguirre Andrew J. , Wolpin Brian M. , Wennerberg Krister , Rudloff Udo , Cox Adrienne D. , Der Channing J. 
Published: October 2019

AbstractAllele-specific signaling by different KRAS alleles remains poorly understood. The KRASG12R mutation displays uneven prevalence among cancers that harbor the highest occurrence of KRAS mutations: It is rare (∼1%) in lung and colorectal cancers, yet relatively common (∼20%) in pancreatic ductal adenocarcinoma (PDAC), suggesting context-specific properties. We evaluated whether KRASG12R is functionally distinct from the more common KRASG12D- or KRASG12V-mutant proteins (KRASG12D/V). We found that KRASG12D/V but not KRASG12R drives macropinocytosis and that MYC is essential for macropinocytosis in KRASG12D/V- but not KRASG12R-mutant PDAC. Surprisingly, we found that KRASG12R is defective for interaction with a key effector, p110α PI3K (PI3Kα), due to structural perturbations in switch II. Instead, upregulated KRAS-independent PI3Kγ activity was able to support macropinocytosis in KRASG12R-mutant PDAC. Finally, we determined that KRASG12R-mutant PDAC displayed a distinct drug sensitivity profile compared with KRASG12D-mutant PDAC but is still responsive to the combined inhibition of ERK and autophagy.Significance:We determined that KRASG12R is impaired in activating a key effector, p110α PI3K. As such, KRASG12R is impaired in driving macropinocytosis. However, overexpression of PI3Kγ in PDAC compensates for this deficiency, providing one basis for the prevalence of this otherwise rare KRAS mutant in pancreatic cancer but not other cancers.See related commentary by Falcomatà et al., p. 23.This article is highlighted in the In This Issue feature, p. 1