bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoxia–ischemia is not an antecedent of most preterm brain damage: the illusion of validity
Authors: Gilles Floyd , Gressens Pierre , Dammann Olaf , Leviton Alan 
Published: June 2017

Brain injury in preterm newborn infants is often attributed to hypoxia–ischemia even when neither hypoxia nor ischemia is documented, and many causative speculations are based on the same assumption. We review human and animal study contributions with their strengths and limitations, and conclude that – despite all the work done in human fetal neuropathology and developmental models in animals – the evidence remains unconvincing that hypoxemia, in the fetus or newborn infant, contributes appreciably to any encephalopathy of prematurity. Giving an inappropriate causal name to a disorder potentially limits the options for change, should our understanding of the etiologies advance. The only observationally‐based title we think appropriate is ‘encephalopathy of prematurity’. Future pathophysiological research should probably include appropriately designed epidemiology studies, highly active developmental processes, infection and other inflammatory stimuli, the immature immune system, long chain fatty acids and their transporters, and growth (neurotrophic) factors.What this paper adds

Fetal hypoxemia is rarely documented in brain injury studies.

Animal studies fail to consider human–animal fetal anatomical differences.

Putative treatments from animal models have not found clinical use.

Observational studies constitute the only approach to etiological understanding.

No convincing evidence yet that hypoxemia injures preterm brain. Encephalopathy of prematurity is preferable to hypoxia‐ischemia as a term for this disorder.

Encephalopathy of prematurity is preferable to hypoxia‐ischemia as a term for this disorder.
Therapeutic inertia in patients treated with two or more antidiabetics in primary care: Factors predicting intensification of treatment
Authors: Mata‐Cases Manel , Franch‐Nadal Josep , Real Jordi , Gratacòs Mònica , López‐Simarro Flora , Khunti Kamlesh , Mauricio Dídac 
Published: June 2017

AimsTo determine the patterns and predictors of treatment intensification in patients with type 2 diabetes on ≥2 non‐insulin antidiabetic drugs (NIADs) and inadequate glycaemic control in primary care in Catalonia, Spain.Material and MethodsThis was a retrospective analysis using electronic medical records from patients with HbA1c ≥ 7% and a first prescription for a new NIAD or insulin recorded from January 2010 to December 2014. Therapeutic inertia was defined as no intensification if HbA1c was ≥8% at baseline or during follow‐up. Time to first intensification was evaluated by time‐to‐event analysis, and factors predicting intensification through a competing‐risk regression model.ResultsAmong 23 678 patients with HbA1c ≥ 7%, 26.2% were censored without treatment intensification after a median follow up of 4.2 years. Among the 12 730 patients in the subgroup with HbA1c ≥ 8% at baseline or during follow‐up, therapeutic inertia was present in 18.1% of cases. In the overall cohort, mean HbA1c at initiation of insulin and NIAD were 9.4% ± 1.5% and 8.7% ± 1.3%, respectively. Median time to first intensification was 17.1 months in patients with HbA1c 8.0% to 9.9%, and 10.1 months in those with HbA1c > 10%. Variables strongly associated with intensification were HbA1c values 8.0% to 9.9% (subhazard ratio [SHR], 1.7; 95% CI, 1.65‐1.78) and >10% (SHR, 2.5; 95% CI, 2.37‐2.68); diabetes duration ≥20 years (SHR, 1.25; 95% CI, 1.11‐1.41) and, to a lesser extent, female gender, presence of comorbidities, chronic kidney disease and microvascular complications.ConclusionsIntensification was not undertaken in 1 in 5 patients. Both HbA1c thresholds and time until therapy intensification exceeded current recommendations.
Projections of climate‐driven changes in tuna vertical habitat based on species‐specific differences in blood oxygen affinity
Authors: Mislan K. A. S. , Deutsch Curtis A. , Brill Richard W. , Dunne John P. , Sarmiento Jorge L. 
Published: June 2017

AbstractOxygen concentrations are hypothesized to decrease in many areas of the ocean as a result of anthropogenically driven climate change, resulting in habitat compression for pelagic animals. The oxygen partial pressure,pO2, at which blood is 50% saturated (P50) is a measure of blood oxygen affinity and a gauge of the tolerance of animals for low ambient oxygen. Tuna species display a wide range of blood oxygen affinities (i.e., P50values) and therefore may be differentially impacted by habitat compression as they make extensive vertical movements to forage on subdaily time scales. To project the effects of end‐of‐the‐century climate change on tuna habitat, we calculate tuna P50depths (i.e., the vertical position in the water column at which ambientpO2is equal to species‐specific blood P50values) from 21st century Earth System Model (ESM) projections included in the fifth phase of the Climate Model Intercomparison Project (CMIP5). Overall, we project P50depths to shoal, indicating likely habitat compression for tuna species due to climate change. Tunas that will be most impacted by shoaling are Pacific and southern bluefin tunas—habitat compression is projected for the entire geographic range of Pacific bluefin tuna and for the spawning region of southern bluefin tuna. Vertical shifts in P50depths will potentially influence resource partitioning among Pacific bluefin, bigeye, yellowfin, and skipjack tunas in the northern subtropical and eastern tropical Pacific Ocean, the Arabian Sea, and the Bay of Bengal. By establishing linkages between tuna physiology and environmental conditions, we provide a mechanistic basis to project the effects of anthropogenic climate change on tuna habitats.
Poor adherence to chronic obstructive pulmonary disease medications in primary care: Role of age, disease burden and polypharmacy
Authors: Vetrano Davide L. , Bianchini Elisa , Onder Graziano , Cricelli Iacopo , Cricelli Claudio , Bernabei Roberto , Bettoncelli Germano , Lapi Francesco 
Published: June 2017

AbstractAimThe aim of the present study was to assess the occurrence and determinants of poor adherence to pharmacological treatment in a cohort of primary care patients with chronic obstructive pulmonary disease (COPD), paying special attention to the role of age, comorbidity and polypharmacy.MethodsWe identified a cohort of COPD patients using the primary care Italian Health Search – IMS Longitudinal Patient Database. We assessed 1‐year adherence to COPD maintenance pharmacotherapy (encompassing inhaled corticosteroids, long‐acting beta agonists and long‐acting anticholinergics). Poor adherence was defined as <80% of proportion of days covered by pharmacological treatment over a 1‐year period.ResultsOf 22 505 patients (mean age 67.3 ± 13.2; 41.3% women) entering the study, 17 486 (77.7%) were poorly adherent. According to multivariate analysis, poor adherence is less likely in older adults (OR 0.51, 95% CI 0.40–0.66), in non‐smokers (OR 0.77, 95% CI 0.69–0.86) and in those with a history of alcohol abuse (OR 0.74, 95% CI 0.58–0.94). Higher comorbidity (OR 1.43, 95% CI 1.13–1.80) was positively associated with poor adherence. Polypharmacy was associated with poor adherence only in patients aged ≥65 years (OR 1.34, 95% CI 1.13–1.59). Finally, COPD severity was associated with a reduced likelihood of poor adherence (OR 0.20, 95% CI 0.07–0.61 for stage IV).ConclusionsThe present findings show that poor medication adherence is common in patients with COPD receiving long‐term treatment. The interaction between age and polypharmacy, and the role of comorbidity suggest a pivotal role of biological age as a steering determinant of poor adherence. Geriatr Gerontol Int 2017; 17: 2500–2506.
Chromosomal abnormalities of high‐grade mucinous tubular and spindle cell carcinoma of the kidney
Authors: Sadimin Evita T , Chen Ying‐Bei , Wang Lu , Argani Pedram , Epstein Jonathan I 
Published: June 2017

AimsMucinous tubular and spindle cell carcinoma (MTSC) of the kidney is a distinct entity characterized by bland tightly packed elongated tubules and spindle cells with low nucleolar grade in a basophilic mucinous stroma. Several case studies have reported MTSC with high‐grade features and have brought into question whether they represented MTSC or a variant of papillary renal cell carcinoma.Methods and resultsWe searched our pathology database and identified seven cases: six MTSC with high International Society of Urological Pathology (ISUP) nucleolar grade and one MTSC with overall low nucleolar grade but extensive necrosis. DNA samples were extracted from paraffin blocks and analysed using a single nucleotide polymorphism (SNP) array platform. Six of seven patients were female, aged between 46 and 82 years. Tumour sizes ranged from 3 to 7.5 cm. One case showed involvement of renal sinus fat and a second case showed involvement of the perinephric fat. All cases shared common chromosomal abnormalities observed with the more typical MTSC, with monosomy of chromosomes 1, 4, 6, 8, 9, 13, 14, 15 and 22. Trisomy of chromosomes 7, 17 and loss of Y chromosome were not observed in any of the cases. None of the patients showed evidence of recurrence or metastasis.DiscussionThe molecular analysis performed in this study supports that MTSC of the kidney can have high nucleolar grade or extensive necrosis, and that they are not papillary renal cell carcinoma. We support modifying the definition of MTSC to include those with higher nucleolar grade.
Interplay between barrier epithelial cells and dendritic cells in allergic sensitization through the lung and the skin
Authors: Deckers Julie , De Bosscher Karolien , Lambrecht Bart N , Hammad Hamida 
Published: June 2017

SummaryThe prevalence of asthma is increasing over the years and it has become obvious that a thorough understanding of mechanisms leading to Th2 sensitization and to asthma is urgently needed to provide better ways to treat the disease. This articles reviews the different players involved in the initiation of allergic reactions in the lung and in the skin, and highlights the importance of a crosstalk between antigen‐presenting dendritic cells and structural cell‐derived signals in this process. Our increasing understanding of these mechanisms indicates that structural cells, such as airway epithelial cells and skin keratinocytes, need to be considered as more than a simple physical barrier since they are very upstream of the entire Th2 cascade and therefore might represent crucial targets for new therapies.
Modeling TH2 responses and airway inflammation to understand fundamental mechanisms regulating the pathogenesis of asthma
Authors: Foster Paul S. , Maltby Steven , Rosenberg Helene F. , Tay Hock L. , Hogan Simon P. , Collison Adam M. , Yang Ming , Kaiko Gerard E. , Hansbro Philip M. , Kumar Rakesh K. , Mattes Joerg 
Published: June 2017

SummaryIn this review, we highlight experiments conducted in our laboratories that have elucidated functional roles for CD4+ T‐helper type‐2 lymphocytes (TH2 cells), their associated cytokines, and eosinophils in the regulation of hallmark features of allergic asthma. Notably, we consider the complexity of type‐2 responses and studies that have explored integrated signaling among classical TH2 cytokines (IL‐4, IL‐5, and IL‐13), which together with CCL11 (eotaxin‐1) regulate critical aspects of eosinophil recruitment, allergic inflammation, and airway hyper‐responsiveness (AHR). Among our most important findings, we have provided evidence that the initiation of TH2 responses is regulated by airway epithelial cell‐derived factors, including TRAIL and MID1, which promote TH2 cell development via STAT6‐dependent pathways. Further, we highlight studies demonstrating that microRNAs are key regulators of allergic inflammation and potential targets for anti‐inflammatory therapy. On the background of TH2 inflammation, we have demonstrated that innate immune cells (notably, airway macrophages) play essential roles in the generation of steroid‐resistant inflammation and AHR secondary to allergen‐ and pathogen‐induced exacerbations. Our work clearly indicates that understanding the diversity and spatiotemporal role of the inflammatory response and its interactions with resident airway cells is critical to advancing knowledge on asthma pathogenesis and the development of new therapeutic approaches.
Crucial role for CD69 in allergic inflammatory responses: CD69‐Myl9 system in the pathogenesis of airway inflammation
Authors: Kimura Motoko Y. , Hayashizaki Koji , Tokoyoda Koji , Takamura Shiki , Motohashi Shinichiro , Nakayama Toshinori 
Published: June 2017

SummaryCD69 has been known as an early activation marker of lymphocytes; whereas, recent studies demonstrate that CD69 also has critical functions in immune responses. Early studies using human samples revealed the involvement of CD69 in various inflammatory diseases including asthma. Moreover, murine disease models using Cd69−/− mice and/or anti‐CD69 antibody (Ab) treatment have revealed crucial roles for CD69 in inflammatory responses. However, it had not been clear how the CD69 molecule contributes to the pathogenesis of inflammatory diseases. We recently elucidated a novel mechanism, in which the interaction between CD69 and its ligands, myosin light chain 9, 12a and 12b (Myl9/12) play a critical role in the recruitment of activated T cells into the inflammatory lung. In this review, we first summarize CD69 function based on its structure and then introduce the evidence for the involvement of CD69 in human diseases and murine disease models. Then, we will describe how we discovered CD69 ligands, Myl9 and Myl12, and how the CD69‐Myl9 system regulates airway inflammation. Finally, we will discuss possible therapeutic usages of the blocking Ab to the CD69‐Myl9 system.
An examination of advanced practice nurses’ job satisfaction internationally
Authors: Steinke M.K. , Rogers M. , Lehwaldt D. , Lamarche K. 
Published: June 2017

AimTo examine the level of job satisfaction of nurse practitioners/advanced practice nurses in developing and developed countries.BackgroundThe nurse practitioner/advanced practice nurse has the advanced, complex skills and experience to play an important role in providing equitable health care across all nations.IntroductionKey factors that contribute to health disparities include lack of access to global health human resources, the right skill mix of healthcare providers and the satisfaction and retention of quality workers.MethodsThe study utilized a descriptive analysis and cross‐sectional survey methodology with quantitative and qualitative sections of 1419 job satisfaction survey respondents from an online survey.ResultsAge, number of hours worked in a week and length of time that nurse practitioners/advanced practice nurses worked in their current jobs were statistically significant in job satisfaction. A key barrier was the lack of respect from supervisors and physicians.DiscussionIt was clear from the number of comments in the qualitative section of the survey that having a wide scope of practice is rewarding and challenging to the nurse practitioner and advanced practice nurse.Conclusion and implications for health policyThe challenges to transform healthcare gaps of access into a better distribution of health care in all countries would constitute a systematic change in policy including providing education and training for doctors and nurses that will match the skills needed in the workplace; emphasizing the right skill mix for the healthcare team; supporting advanced practice nurses in the workplace; and utilizing all healthcare providers to the fullest extent of their abilities.
Melatonin protects against maternal obesity‐associated oxidative stress and meiotic defects in oocytes via the SIRT3‐SOD2‐dependent pathway
Authors: Han Longsen , Wang Haichao , Li Ling , Li Xiaoyan , Ge Juan , Reiter Russel J. , Wang Qiang 
Published: June 2017

AbstractMaternal obesity in humans is associated with poor outcomes across the reproductive spectrum. Emerging evidence indicates that these defects are likely attributed to factors within the oocyte. Although various molecules and pathways may contribute to impaired oocyte quality, prevention of fertility issues associated with maternal obesity is a challenge. Using mice fed a high‐fat diet (HFD) as an obesity model, we document spindle disorganization, chromosome misalignment, and elevated reactive oxygen species (ROS) levels in oocytes from obese mice. Oral administration of melatonin to HFD mice not only reduces ROS generation, but also prevents spindle/chromosome anomalies in oocytes, consequently promoting the developmental potential of early embryos. Consistent with this finding, we find that melatonin supplement during in vitro maturation also markedly attenuates oxidative stress and meiotic defects in HFD oocytes. Finally, by performing morpholino knockdown and acetylation‐mimetic mutant overexpression assays, we reveal that melatonin ameliorates maternal obesity‐induced defective phenotypes in oocytes through the SIRT3‐SOD2‐dependent mechanism. In sum, our data uncover the marked beneficial effects of melatonin on oocyte quality from obese females; this opens a new area for optimizing culture system as well as fertility management.
Hepatitis C virus infection and risk of multiple myeloma: Evidence from a meta‐analysis based on 17 case‐control studies
Authors: Li Y. , Li Y. , Zhang L. , Li W. 
Published: June 2017

SummaryHepatitis C virus (HCV) infection is a leading cause of chronic liver damage and is associated with other diseases. Some studies reported that patients with HCV have a significantly increased risk of multiple myeloma while others do not report an association. We aimed to clarify the association between HCV and multiple myeloma and analyse the factors that affect the controversial conclusions through a meta‐analysis. We conducted a systematic literature search of HCV and myeloma in the databases of PubMed/MEDLINE, Cochrane Library, EMBASE, Wanfang and China National Knowledge Infrastructure (CNKI) from inception to September 2016. Outcomes were expressed as odds ratios (ORs) and 95% confidence intervals (95% CIs). A positive correlation between HCV infection and risk of developing multiple myeloma was revealed (OR=2.67, 95% CI=1.35‐5.26, P=.005) based on meta‐analysis of 17 case‐control observational studies. When the data were stratified by source of control, significant associations were observed in hospital‐based studies, but not population‐based studies. Further subgroup analyses showed increased risk of multiple myeloma in HCV patients when studies were conducted in high HCV prevalent countries, but not in low or moderate HCV prevalent countries. In addition, similar positive association was detected in studies performed in the East Asia and in intermediate‐quality studies. In summary, the association of HCV infection with increased risk of multiple myeloma depended on several factors, including study design, quality and environmental HCV prevalence. Further large‐scale, well‐designed studies are needed to validate the role of HCV in the aetiology of multiple myeloma.
Negative regulation of filamentous growth in Candida albicans by Dig1p
Authors: Regan Hannah , Scaduto Christine M. , Hirakawa Matthew P. , Gunsalus Kearney , Correia‐Mesquita Tuana Oliveira , Sun Yuan , Chen Yaolin , Kumamoto Carol A. , Bennett Richard J. , Whiteway Malcolm 
Published: June 2017

SummaryTranscriptional regulation involves both positive and negative regulatory elements. The Dig1 negative regulators are part of a fungal‐specific module that includes a transcription factor (a Ste12 family member) and a Dig1 family member. In Saccharomyces cerevisiae, the post‐genome‐duplication Dig1/Dig2 proteins regulate MAP kinase controlled signalling pathways involved in mating and filamentous growth. We have identified the single Dig1 orthologue in the fungal pathogen Candida albicans. Genetic studies and transcriptional profiling experiments show that this single protein is implicated in the regulation of MAP kinase‐controlled processes involved in mating, filamentous growth and biofilm formation, and also influences cAMP‐regulated processes. This suggests that the multiple cellular roles of the Dig1 protein are ancestral and predate the sub‐functionalization apparent in S. cerevisiae after the genome duplication. Intriguingly, even though loss of Dig1 function in C. albicans enhances filamentous growth and biofilm formation, colonization of the murine gastrointestinal tract is reduced in the mutant. The complexity of the processes influenced by Dig1 in C. albicans, and the observation that Dig1 is one of the few regulatory proteins that were retained in the duplicated state after the whole genome duplication event in yeast, emphasizes the important role of these negative regulators in fungal transcriptional control.
Genetic diversity and antifungal susceptibility of Fusarium isolates in onychomycosis
Authors: Rosa Priscila D. , Heidrich Daiane , Corrêa Carolina , Scroferneker Maria Lúcia , Vettorato Gerson , Fuentefria Alexandre M. , Goldani Luciano Z. 
Published: June 2017

SummaryFusarium species have emerged as an important human pathogen in skin disease, onychomycosis, keratitis and invasive disease. Onychomycosis caused by Fusarium spp. The infection has been increasingly described in the immunocompetent and immunosuppressed hosts. Considering onychomycosis is a difficult to treat infection, and little is known about the genetic variability and susceptibility pattern of Fusarium spp., further studies are necessary to understand the pathogenesis and better to define the appropriate antifungal treatment for this infection. Accordingly, the objective of this study was to describe the in vitro susceptibility to different antifungal agents and the genetic diversity of 35 Fusarium isolated from patients with onychomycosis. Fusarium spp. were isolated predominantly from female Caucasians, and the most frequent anatomical location was the nail of the hallux. Results revealed that 25 (71.4%) of isolates belonged to the Fusarium solani species complex, followed by 10 (28.5%) isolates from the Fusarium oxysporum species complex. Noteworthy, the authors report the first case of Neocosmospora rubicola isolated from a patient with onychomycosis. Amphotericin B was the most effective antifungal agent against the majority of isolates (60%, MIC ≤4 μg/mL), followed by voriconazole (34.2%, MIC ≤4 μg/mL). In general, Fusarium species presented MIC values >64 μg/mL for fluconazole, itraconazole and terbinafine. Accurate pathogen identification, characterisation and susceptibility testing provide a better understanding of pathogenesis of Fusarium in onychomycosis.
The great trade collapse and Indian firms
Authors: Chakraborty Pavel 
Published: June 2017

AbstractThe collapse in global trade during the 2008–09 crisis has been widely studied using the developed nation(s) data. I use firm‐level data from Indian manufacturers to show that: (a) Indian firms experience strong negative demand shocks concerning their exports to the USA and the EU, the effect being significantly higher in case of the USA. Results assert that 1% increase in the exposure towards the crisis‐affected zones (the USA and the EU combined) reduces an average Indian manufacturing firm's export earnings by 1.17%–1.36%; (b) trade in consumer non‐durables and durables are the two most affected sectors, impact being higher for the latter; (c) evidence in support of similar effects throughout the size distribution of firms, with the effect being highest for small or the most vulnerable firms; (d) drop in demand, as a result of the 2008–09 crisis, only affects the high‐exposure industries. My results are robust to IV analysis and a variety of checks.