bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepcidin-(In)dependent Mechanisms of Iron Metabolism Regulation during Infection by Listeria and Salmonella
Authors: Moreira Ana C. , Neves João V. , Silva Tânia , Oliveira Patrícia , Gomes Maria S. , Rodrigues Pedro N. 
Published: June 2017

ABSTRACT

During bacterial infection, the pathogenic agent and the host battle for iron, due to its importance for fundamental cellular processes. However, iron redistribution and sequestration during infection can culminate in anemia. Although hepcidin has been recognized as the key regulator of iron metabolism, in some infections its levels remain unaffected, suggesting the involvement of other players in iron metabolism deregulation. In this work, we use a mouse model to elucidate the main cellular and molecular mechanisms that lead to iron redistribution during infection with two different pathogens:
Listeria monocytogenes
and
Salmonella enterica
serovar Typhimurium. Both infections clearly impacted iron metabolism, causing iron redistribution, decreasing serum iron levels, decreasing the saturation of transferrin, and increasing iron accumulation in the liver. Both infections were accompanied by the release of proinflammatory cytokines. However, when analyzing iron-related gene expression in the liver, we observed that hepcidin was induced by
S
. Typhimurium but not by
L. monocytogenes
. In the latter model, the downregulation of hepatic ferroportin mRNA and protein levels suggested that ferroportin plays a major role in iron redistribution. On the other hand,
S
. Typhimurium infection induced the expression of hepcidin mRNA, and we show here, for the first time
in vivo
, that this induction is Toll-like receptor 4 (TLR4) dependent. In this work, we compare several aspects of iron metabolism alterations induced by two different pathogens and suggest that hepcidin-(in)dependent mechanisms contribute to iron redistribution upon infection.
Reducing patient waiting time and length of stay in an Acute Care Pediatric Emergency Department
Authors: Al-Onazi Milfi , Al Hajri Ahmed , Caswell Angela , Leizl Hugo Villanueva Maria , Mohammed Zuhair , Esteves Vania , Vabasa Faith , Al-Surimi Khaled 
Published: June 2017

Prolonged waiting times and length of stay in Pediatric Emergency Department, are the two of the most challenging patient and clinical outcomes of healthcare institution. These emerged due to various reasons, namely: the use of triaging process and patient flow criteria that eventually lead to bottlenecks and overcrowding in the ED. After realizing the root causes of the prolonged waiting times and length of stay, the KASCH ED instigated a team to study the factors and thereby arrive at a considerable conclusion that will result in an improvement.The quality improvement project was initiated and steps were undertaken to improve the flow, reduce the waiting times, and reduce the overcrowding in Pediatric Emergency Acute Care Unit. The primary cause identified was inadequate team awareness and lack of the ED process flow, thus creating confusion as to where the type of patients based on the triage level will be assessed, managed and treated. Using the Canadian Triage and Acuity Scale (CTAS) as guide in triaging patients, a theory called Pediatric Rapid Assessment and Management (PRAM) was introduced in the Acute Care Unit. This certain model is basically aimed to rapidly assess and managed the patients who were triaged as Level III and Level IV within a period of 30 minutes.Several PDSA cycles were tested and implemented in order to assure that the process fit the criteria and the process flow will be improved. Following the completion of each cycle, significant improvements were noted, such as patients being assessed in Initial Assessment Room on average time less than the target of 15 minutes. In like manner, patients' length of stay on average less than 15 minutes in PRAM bed. The total time for assessment and plan of management is with a target time of less than 30 minutes. The team continuously drive th process and monitored the key performance indicators of the PRAM during the study period and subsequent improvement strategies were likewise implemented.
Complement levels and risk of organ involvement in patients with systemic lupus erythematosus
Authors: Gandino Ignacio Javier , Scolnik Marina , Bertiller Emmanuel , Scaglioni Valeria , Catoggio Luis Jose , Soriano Enrique Roberto 
Published: June 2017

ObjectiveComplement plays a major role in SLE. Complement participation has been linked to disease activity and damage. Our objective was to estimate the association of complement behaviour with clinical manifestations, visceral injury and mortality in patients with SLE.MethodsComplement determinations (C3 and C4 levels) were analysed in patients with SLE (fulfilling American College of Rheumatology (ACR) or Systemic Lupus International Collaborating Clinics (SLICC)criteria) seen at a university hospital between 2000 and 2013. Patients were grouped in those with permanent C3 and/or C4 low values (low complement group), those with C3 and C4 constant normal values (normal complement group) and those with fluctuant values (periods of normal and periods of low values: fluctuant group). Clinical characteristics and mortality were analysed and compared between groups.Results270 patients with SLE were included (242 females, 89.6%), mean age at diagnosis was 34.2 years (SD 15.8). 75 patients had fluctuant levels of complement, 79 patients had persistent low complement levels and 116 had normal complement levels. Lupus glomerulonephritis was more frequent in patients with fluctuant levels (75%, 56% and 49%, respectively, p=0002). The normal complement group had less frequency of haematological involvement and anti-double stranded DNA (dsDNA) antibodies. At the end of the follow-up, 53% of the patients had damage (SLICC/ACR ≥1). In a Cox proportional hazard model age at diagnosis, neurological impairment, thrombocytopaenia and corticosteroids were associated with more damage, while hydroxychloroquine was a protective factor. There were no differences between complements groups on accumulated damage. Ten-year survival rate was 93%, 93.5% and 92% for the normal complement group, the persistently low group and the fluctuant group, respectively.ConclusionsPatients with constant normal complement had lower prevalence of haematological involvement and anti-dsDNA, while patients with fluctuant complement had higher renal impairment. Neither the persistent low complement nor the fluctuant complement groups had increased mortality and/or visceral damage.
LIFTING CAPACITY AMONG INDIAN MANUAL MATERIALS HANDLERS USING PROGRESSIVE ISOINERTIAL LIFTING EVALUATION
Authors: Girish N. , Iqbal Rauf , Khanzode Vivek 
Published: June 2017

Purpose: Weight of the load which is to be lifted and its characteristics are considered to be important risk factors for low back disorders (LBD) among manual material handlers. Determining the amount of load a person can lift is important in minimizing the incidence of LBD. The objective of this study was to determine the lifting capacity, adopting two lifting techniques at two levels among male construction workers using progressive isoinertial lifting evaluation (PILE). Methods: One hundred and forty-three male construction workers with minimum 1 year of work experience and without any acute illnesses participated in this study. Workers were advised to perform PILE using two lifting techniques (stoop and squat) and at two lifting levels (waist and shoulder). Results: The mean lifting capacity was found to be 24.50 [Formula: see text] 5.10, 21.20 [Formula: see text] 5.54, 19.76 [Formula: see text] 4.08 and 17.25 [Formula: see text] 5.18 kg, respectively, for floor to waist-stoop, floor to waist-squat, floor to shoulder-stoop and floor to shoulder-squat categories. The lifting capacity decreased by 19.40% and 18.54% when the vertical distance was increased from waist to shoulder adopting stoop and squat techniques, respectively. Conclusion: Lifting capacity for construction workers has been determined using PILE, and it was found to be more during stoop technique of lifting at floor to waist level.
Hypoxia-Induced Downregulation of DUSP-2 Phosphatase Drives Colon Cancer Stemness
Authors: Hou Pei-Chi , Li Yo-Hua , Lin Shih-Chieh , Lin Shau-Chieh , Lee Jenq-Chang , Lin Bo-Wen , Liou Jing-Ping , Chang Jang-Yang , Kuo Ching-Chuan , Liu Yi-Min , Sun H. Sunny , Tsai Shaw-Jenq 
Published: June 2017

Abstract
Cancer stem-like cells (CSC) evolve to overcome the pressures of reduced oxygen, nutrients or chemically induced cell death, but the mechanisms driving this evolution are incompletely understood. Here, we report that hypoxia-mediated downregulation of the dual specificity phosphatase 2 (DUSP2) is critical for the accumulation of CSC in colorectal cancer. Reduced expression of DUSP2 led to overproduction of COX-2–derived prostaglandin E2, which promoted cancer stemness via the EP2/EP4 signaling pathways. Genetic and pharmacological inhibition of PGE2 biosynthesis or signal transduction ameliorated loss-of-DUSP2–induced tumor growth and cancer stemness. Genome-wide profile analysis revealed that genes regulated by DUSP2 were similar to those controlled by histone deacetylase. Indeed, treatment with novel histone deacetylase inhibitors abolished hypoxia-induced DUSP2 downregulation, COX-2 overexpression, cancer stemness, tumor growth, and drug resistance. Our findings illuminate mechanisms of cancer stemness and suggest new cancer therapy regimens. Cancer Res; 77(16); 4305–16. ©2017 AACR.
WEE1 Kinase Inhibitor AZD1775 Has Preclinical Efficacy in LKB1-Deficient Non–Small Cell Lung Cancer
Authors: Richer Amanda L. , Cala Jacqueline M. , O'Brien Kelley , Carson Vashti M. , Inge Landon J. , Whitsett Timothy G. 
Published: June 2017

Abstract
G1–S checkpoint loss contributes to carcinogenesis and increases reliance upon the G2–M checkpoint for adaptation to stress and DNA repair, making G2–M checkpoint inhibition a target for novel therapeutic development. AZD1775, an inhibitor against the critical G2–M checkpoint protein WEE1, is currently in clinical trials across a number of tumor types. AZD1775 and DNA-damaging agents have displayed favorable activity in several preclinical tumor models, often in the molecular context of TP53 loss. Whether AZD1775 efficacy is modulated by other molecular contexts remains poorly understood. The tumor suppressor serine/threonine kinase 11 (LKB1/STK11) is one of the most frequently mutated genes in non–small cell lung cancer (NSCLC) and is commonly comutated with oncogenic KRAS mutations. We investigated the preclinical effects of AZD1775 in the context of KRAS/LKB1 in NSCLC. Using NSCLC cell lines, we found that AZD1775 alone and in combination with DNA-damaging agents (e.g., cisplatin and radiation) decreased tumor cell viability in LKB1-deficient NSCLC cells. In vitro, LKB1 deficiency enhanced DNA damage and apoptosis in response to AZD1775 exposure compared with wild-type LKB1 cells. In a genetically engineered mouse model of mutant Kras with concomitant loss of Lkb1, combined AZD1775 and cisplatin extended overall survival compared with cisplatin alone. Our data suggest that lack of phosphorylation of LKB1 by ATM was involved in AZD1775-mediated cytotoxicity. Collectively, these findings provide a clinical application for AZD1775 with DNA-damaging agents in KRAS/LKB1 NSCLC. Cancer Res; 77(17); 4663–72. ©2017 AACR.
SPIN90 Depletion and Microtubule Acetylation Mediate Stromal Fibroblast Activation in Breast Cancer Progression
Authors: You Eunae , Huh Yun Hyun , Kwon Ahreum , Kim So Hee , Chae In Hee , Lee Ok-Jun , Ryu Je-Hwang , Park Min Ho , Kim Ga-Eon , Lee Ji Shin , Lee Kun Ho , Lee Yong-Seok , Kim Jung-Woong , Rhee Sangmyung , Song Woo Keun 
Published: June 2017

Abstract
Biomechanical remodeling of stroma by cancer-associated fibroblasts (CAF) in early stages of cancer is critical for cancer progression, and mechanical cues such as extracellular matrix stiffness control cell differentiation and malignant progression. However, the mechanism by which CAF activation occurs in low stiffness stroma in early stages of cancer is unclear. Here, we investigated the molecular mechanism underlying CAF regulation by SPIN90 and microtubule acetylation under conditions of mechanically soft matrices corresponding to normal stromal rigidity. SPIN90 was downregulated in breast cancer stroma but not tumor, and this low stromal expression correlated with decreased survival in breast cancer patients. Spin90 deficiency facilitated recruitment of mDia2 and APC complex to microtubules, resulting in increased microtubule acetylation. This increased acetylation promoted nuclear localization of YAP, which upregulated expression of myofibroblast marker genes on soft matrices. Spin90 depletion enhanced tumor progression, and blockade of microtubule acetylation in CAF significantly inhibited tumor growth in mice. Together, our data demonstrate that loss of SPIN90-mediated microtubule acetylation is a key step in CAF activation in low stiffness stroma. Moreover, correlation among these factors in human breast cancer tissue supports the clinical relevance of SPIN90 and microtubule acetylation in tumor development. Cancer Res; 77(17); 4710–22. ©2017 AACR.
Unpaired Extracellular Cysteine Mutations of CSF3R Mediate Gain or Loss of Function
Authors: Zhang Haijiao , Means Sophie , Schultz Anna Reister , Watanabe-Smith Kevin , Medeiros Bruno C. , Bottomly Daniel , Wilmot Beth , McWeeney Shannon K. , Kükenshöner Tim , Hantschel Oliver , Tyner Jeffrey W. 
Published: June 2017

Abstract
Exclusive of membrane-proximal mutations seen commonly in chronic neutrophilic leukemia (e.g., T618I), functionally defective mutations in the extracellular domain of the G-CSF receptor (CSF3R) have been reported only in severe congenital and idiopathic neutropenia patients. Here, we describe the first activating mutation in the fibronectin-like type III domain of the extracellular region of CSF3R (W341C) in a leukemia patient. This mutation transformed cells via cysteine-mediated intermolecular disulfide bonds, leading to receptor dimerization. Interestingly, a CSF3R cytoplasmic truncation mutation (W791X) found on the same allele as the extracellular mutation and the expansion of the compound mutation was associated with increased leukocytosis and disease progression of the patient. Notably, the primary patient sample and cells transformed by W341C and W341C/W791X exhibited sensitivity to JAK inhibitors. We further showed that disruption of original cysteine pairs in the CSF3R extracellular domain resulted in either gain- or loss-of-function changes, part of which was attributable to cysteine-mediated dimer formation. This, therefore, represents the first characterization of unpaired cysteines that mediate both gain- and loss-of-function phenotypes. Overall, our results show the structural and functional importance of conserved extracellular cysteine pairs in CSF3R and suggest the necessity for broader screening of CSF3R extracellular domain in leukemia patients. Cancer Res; 77(16); 4258–67. ©2017 AACR.
Enhancing Spatial Attention and Working Memory in Younger and Older Adults
Authors: Rolle Camarin E. , Anguera Joaquin A. , Skinner Sasha N. , Voytek Bradley , Gazzaley Adam 
Published: June 2017

Abstract
Daily experiences demand both focused and broad allocation of attention for us to interact efficiently with our complex environments. Many types of attention have shown age-related decline, although there is also evidence that such deficits may be remediated with cognitive training. However, spatial attention abilities have shown inconsistent age-related differences, and the extent of potential enhancement of these abilities remains unknown. Here, we assessed spatial attention in both healthy younger and older adults and trained this ability in both age groups for 5 hr over the course of 2 weeks using a custom-made, computerized mobile training application. We compared training-related gains on a spatial attention assessment and spatial working memory task to age-matched controls who engaged in expectancy-matched, active placebo computerized training. Age-related declines in spatial attention abilities were observed regardless of task difficulty. Spatial attention training led to improved focused and distributed attention abilities as well as improved spatial working memory in both younger and older participants. No such improvements were observed in either of the age-matched control groups. Note that these findings were not a function of improvements in simple response time, as basic motoric function did not change after training. Furthermore, when using change in simple response time as a covariate, all findings remained significant. These results suggest that spatial attention training can lead to enhancements in spatial working memory regardless of age.
Observations of Increased Cloud Cover over Irrigated Agriculture in an Arid Environment
Authors: Garcia-Carreras Luis , Marsham John H. , Spracklen Dominick V. 
Published: June 2017

Abstract
Irrigated agriculture accounts for 20% of global cropland area and may alter climate locally and globally, but feedbacks on clouds and rainfall remain highly uncertain, particularly in arid regions. Nonrenewable groundwater in arid regions accounts for 20% of global irrigation water demand, and quantifying these feedbacks is crucial for the prediction of long-term water use in a changing climate. Here, satellite data are used to show how irrigated crops in an arid environment alter land surface properties, cloud cover, and rainfall patterns. Land surface temperatures (LSTs) over the cropland are 5–7 K lower than their surroundings, despite a lower albedo, suggesting that Bowen ratio is strongly reduced (and latent heat fluxes increased) over the irrigated cropland. Daytime cloud cover is increased by up to 15% points (a relative increase of 60%), with increased cloud development in the morning and a greater afternoon peak in cloud. Cloud cover is significantly correlated with interannual variations in vegetation and LST. Afternoon rainfall also appears to be enhanced around the irrigation. The cloud feedback is the opposite of what has been previously observed in tropical and semiarid regions, suggesting different processes drive land–atmosphere feedbacks in very dry environments. Increased cloud and rainfall, and associated increases in diffuse radiation and reductions in temperature, are likely to benefit vegetation growth. Predictions of changes in crop productivity due to climate change and the impacts of global land-use change on climate and the use of water resources would therefore benefit from including these effects.
Surgical Complications from Superior Canal Dehiscence Syndrome Repair: Two Decades of Experience
Authors: Xie Yanjun , Sharon Jeffrey D. , Pross Seth E. , Abt Nicholas B. , Varma Sanskriti , Della Santina Charley C. , Minor Lloyd B. , Carey John P. 
Published: June 2017

ObjectiveTo determine the incidence of surgical complications associated with superior canal dehiscence syndrome (SCDS) repair and identify the demographic, medical, and intraoperative risk factors that are associated with SCDS complications.Study DesignCases series with chart review, including patients who underwent SCDS repair between 1996 and 2015.SettingA tertiary care academic medical center.Subjects and MethodsData were collected from 220 patients, including demographic information, medical comorbidities, prior otologic surgical history, surgical approach, intraoperative findings, and postoperative complications. Relative risk analysis and multivariable logistic regression evaluated the associations between perioperative risk factors and SCDS complications.ResultsA total of 242 consecutive cases were performed: 95.5% middle fossa and 4.5% transmastoid approach (mean age: 47.8 ± 10.6 years; 54.5% female). Surgical complications were reported in 27 (11.2%) cases; 20 (8.3%) had Clavien‐Dindo grade I complications, most commonly benign paroxysmal positional vertigo (n = 11, 4.5%) and profound sensorineural hearing loss (n = 6, 2.5%). Two cases (0.8%) had grade II; 4 cases (1.7%), grade III; and 1 case (0.4%), grade IV complications. In the analysis of comorbidities, only preoperative coagulopathy was significantly associated with increased risk of complications (relative risk = 6.4, P <. 01). Following multivariate logistic regression adjusting for demographic covariates, coagulopathy was still associated with increased odds of complications (odds ratio = 15.7, P =. 03). There were no significant associations between other risk factors and complications.ConclusionSCDS repair has low rates of adverse events. We observed an incidence of 11.2% complications, most commonly postoperative benign paroxysmal positional vertigo. The risk of nonotologic intracranial complications (1.7%) is low.
McGill Thyroid Nodule Score in Differentiating Benign and Malignant Pediatric Thyroid Nodules: A Pilot Study
Authors: Canfarotta Michael , Moote Douglas , Finck Christine , Riba‐Wolman Rebecca , Thaker Shefali , Lerer Trudy J. , Payne Richard J. , Cote Valerie 
Published: June 2017

ObjectiveThe McGill Thyroid Nodule Score (MTNS) is a preoperative tool used to predict the risk for well‐differentiated thyroid cancer given a specific nodule in adults. We evaluated the clinical utility of a modified pediatric MTNS with children and adolescents.Study DesignCase series with chart review.SettingTertiary care children’s hospital.Subjects and MethodsThis is a retrospective chart review of 46 patients ≤18 years of age presenting with a solitary or dominant thyroid nodule treated with surgical resection between September 2008 and December 2015. The cumulative MTNS for each nodule was calculated and compared with the final pathology.ResultsOf 46 patients, 10 (21.7%) were diagnosed with well‐differentiated thyroid cancer (80% papillary thyroid carcinoma, 10% follicular variant of papillary thyroid carcinoma, 10% follicular thyroid carcinoma). Malignant nodules were associated with a greater mean MTNS (benign, 5.72 ± 3.03; malignant, 16 ± 3.13; P <. 05). The sensitivity, specificity, and positive predictive value of malignancy were 100%, 94.4%, and 83.3% for scores ≥10 and 80%, 100%, and 100% for scores ≥11, respectively. In nodules with indeterminate cytology (Bethesda III and IV), the pediatric MTNS showed good differentiation between benign and malignant disease, with mean scores of 7.95 and 12.5, respectively (P =. 006).ConclusionThis pilot study suggests that a comprehensive scoring system may help assess the risk of malignancy in pediatric thyroid nodules and differentiate nodules with indeterminate cytology into higher‐ and lower‐risk categories. Given these findings, larger, multi‐institutional studies are warranted.