bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential Climate Change Health Risks from Increases in Heat Waves: Abnormal Birth Outcomes and Adverse Maternal Health Conditions
Authors: Cil Gulcan , Cameron Trudy Ann 
Published: February 2017

AbstractWe investigate the risks presented by heat waves for adverse health conditions for babies and expectant mothers when these mothers have been exposed to heat waves during gestation or during the period just prior to conception. Rather than just birth weight and gestational age, we focus on less common metrics such as abnormal conditions in the newborn (fetal distress, reliance on a ventilator, and meconium aspiration) and adverse health conditions in the mother (pregnancy‐related hypertension, uterine bleeding during pregnancy, eclampsia, and incompetent cervix). We use monthly panel data for over 3,000 U.S. counties, constructed from the confidential version of the U.S. Natality Files for 1989–2008. Our models control for sociodemographic factors and include county, month, and state‐by‐year fixed effects to control for unobserved spatial and timewise heterogeneity in the data. Even within the United States, where there is widespread access to air conditioning, heat waves increase the fraction of babies with abnormal conditions related to maternal stress, as well as the fraction of mothers who experience pregnancy‐related adverse health conditions. The scope for these risks in developing countries is likely to be even greater.
Sizing Up a Superstorm: Exploring the Role of Recalled Experience and Attribution of Responsibility in Judgments of Future Hurricane Risk
Authors: Rickard Laura N. , Yang Z. Janet , Schuldt Jonathon P. , Eosco Gina M. , Scherer Clifford W. , Daziano Ricardo A. 
Published: February 2017

AbstractResearch suggests that hurricane‐related risk perception is a critical predictor of behavioral response, such as evacuation. Less is known, however, about the precursors of these subjective risk judgments, especially when time has elapsed from a focal event. Drawing broadly from the risk communication, social psychology, and natural hazards literature, and specifically from concepts adapted from the risk information seeking and processing model and the protective action decision model, we examine how individuals’ distant recollections, including attribution of responsibility for the effects of a storm, attitude toward relevant information, and past hurricane experience, relate to risk judgment for a future, similar event. The present study reports on a survey involving U.S. residents in Connecticut, New Jersey, and New York (n = 619) impacted by Hurricane Sandy. While some results confirm past findings, such as that hurricane experience increases risk judgment, others suggest additional complexity, such as how various types of experience (e.g., having evacuated vs. having experienced losses) may heighten or attenuate individual‐level judgments of responsibility. We suggest avenues for future research, as well as implications for federal agencies involved in severe weather/natural hazard forecasting and communication with public audiences.
Targets and Mechanisms in Prevention of Parkinson's Disease through Immunomodulatory Treatments
Authors: von Euler Chelpin M. , Vorup‐Jensen T. 
Published: February 2017

AbstractParkinson's disease (PD) is the second most common neurodegenerative disease in the world; however, there is no cure for it. Current treatments only relieve some of the symptoms, without ceasing the disease, and lose efficacy with prolonged treatment. Considerable evidence shows that persistent inflammatory responses, involving T cell infiltration and glial cell activation, are common characteristics of human patients and play a crucial role in the degeneration of dopaminergic neurons. Therefore, it is important to develop therapeutic strategies that can impede or halt the disease through the modulation of the peripheral immune system by aiming at controlling the existing neuroinflammation. Most of the immunomodulatory therapies designed for the treatment of Parkinson′s disease are based on vaccines using AS or antibodies against it; yet, it is of significant interest to explore other formulations that could be used as therapeutic agents. Several vaccination procedures have shown that inducing regulatory T cells in the periphery is protective in PD animal models. In this regard, the formulation glatiramer acetate (Copaxone®), extensively used for the treatment of multiple sclerosis, could be a suitable candidate due to its capability to increase the number and suppressor capacity of regulatory T cells. In this review, we will present some of the recent immunomodulatory therapies for PD including vaccinations with AS or glatiramoids, or both, as treatments of PD pathology.
Investigation of the Role of Protein Kinase D in Human Rhinovirus Replication
Authors: Guedán Anabel , Swieboda Dawid , Charles Mark , Toussaint Marie , Johnston Sebastian L. , Asfor Amin , Panjwani Anusha , Tuthill Tobias J. , Danahay Henry , Raynham Tony , Mousnier Aurelie , Solari Roberto 
Published: February 2017

ABSTRACT
Picornavirus replication is known to cause extensive remodeling of Golgi and endoplasmic reticulum membranes, and a number of the host proteins involved in the viral replication complex have been identified, including oxysterol binding protein (OSBP) and phosphatidylinositol 4-kinase III beta (PI4KB). Since both OSBP and PI4KB are substrates for protein kinase D (PKD) and PKD is known to be involved in the control of Golgi membrane vesicular and lipid transport, we hypothesized that PKD played a role in viral replication. We present multiple lines of evidence in support of this hypothesis. First, infection of HeLa cells with human rhinovirus (HRV) induced the phosphorylation of PKD. Second, PKD inhibitors reduced HRV genome replication, protein expression, and titers in a concentration-dependent fashion and also blocked the replication of poliovirus (PV) and foot-and-mouth disease virus (FMDV) in a variety of cells. Third, HRV replication was significantly reduced in HeLa cells overexpressing wild-type and mutant forms of PKD1. Fourth, HRV genome replication was reduced in HAP1 cells in which the PKD1 gene was knocked out by clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9. Although we have not identified the molecular mechanism through which PKD regulates viral replication, our data suggest that this is not due to enhanced interferon signaling or an inhibition of clathrin-mediated endocytosis, and PKD inhibitors do not need to be present during viral uptake. Our data show for the first time that targeting PKD with small molecules can inhibit the replication of HRV, PV, and FMDV, and therefore, PKD may represent a novel antiviral target for drug discovery.

IMPORTANCE
Picornaviruses remain an important family of human and animal pathogens for which we have a very limited arsenal of antiviral agents. HRV is the causative agent of the common cold, which in itself is a relatively trivial infection; however, in asthma and chronic obstructive pulmonary disease (COPD) patients, this virus is a major cause of exacerbations resulting in an increased use of medication, worsening symptoms, and, frequently, hospital admission. Thus, HRV represents a substantial health care and economic burden for which there are no approved therapies. We sought to identify a novel host target as a potential anti-HRV therapy. HRV infection induces the phosphorylation of PKD, and inhibitors of this kinase effectively block HRV replication at an early stage of the viral life cycle. Moreover, PKD inhibitors also block PV and FMDV replication. This is the first description that PKD may represent a target for antiviral drug discovery.
Endoplasmic Reticulum Protein SCAP Inhibits Dengue Virus NS2B3 Protease by Suppressing Its K27-Linked Polyubiquitylation
Authors: Liu Heng , Zhang Lele , Sun Jin , Chen Wei , Li Senlin , Wang Qiang , Yu Huansha , Xia Zanxian , Jin Xia , Wang Chen 
Published: February 2017

ABSTRACT
Dengue viruses (DENVs) are an emerging threat to global public health. The NS2B3 protease complex of DENV has recently been shown to cleave the antiviral protein STING and thereby subvert the innate immune signaling to facilitate virus replication. Whether host cells have a mechanism to counteract this virus-mediated immunosuppression is unclear. We discovered that the K27-linked polyubiquitination of NS3 protein facilitates its recruitment of NS2B, the formation of NS2B3, and consequently the enhanced cleavage of STING. However, an endoplasmic reticulum (ER) protein, SCAP, through binding to NS2B protein, inhibits the ubiquitination of NS3, rendering NS2B3 protease incapable of binding and cleaving STING. Importantly, ectopic expression of SCAP impaired DENV infection, whereas silencing of SCAP potentiated DENV infection. Collectively, this study uncovered a novel function of SCAP of counteracting the inhibitory action of DENV NS2B3 protease on STING signaling, suggesting that modulation of SCAP levels may have therapeutic implications.

IMPORTANCE
This study reports the first ubiquitylation target protein in DENV, the NS3 protein, and the unique role of K27-linked polyubiquitylation in NS3's ability to recruit NS2B and formation of the NS2B3 protease complex. Additionally, this study identified novel functions of the ER protein SCAP: one is to compete with NS2B for binding to STING, and the other is to inhibit the ubiquitination of NS3. Both of these functions protect STING from being cleaved by the NS2B3 protease and thus contribute to host antiviral response.
Periodontitis as a possible early sign of diabetes mellitus
Authors: Teeuw Wijnand J , Kosho Madeline X F , Poland Dennis C W , Gerdes Victor E A , Loos Bruno G 
Published: February 2017

ObjectiveThe early diagnosis of (pre)diabetes mellitus is essential for the prevention of diabetes complications. It has been suggested that gum disease (periodontitis) might be an early complication of diabetes and may be a useful risk indicator for diabetes screening. Therefore, a dental office could be a good location for screening for (pre)diabetes in patients with periodontitis using a validated glycated hemoglobin (HbA1c) dry spot analysis.Research design and methodsA total of 313 individuals from a university dental clinic participated. From 126 patients with mild/moderate periodontitis, 78 patients with severe periodontitis and 109 subjects without periodontitis, HbA1c values were obtained by the analysis of dry blood spots. Differences in mean HbA1c values and the prevalence of (pre)diabetes between the groups were analyzed.ResultsThe mild/moderate and severe periodontitis groups showed significantly higher HbA1c values (6.1%±1.4% (43 mmol/mol±15 mmol/mol) and 6.3%±1.3% (45 mmol/mol±15 mmol/mol), respectively) compared with the control group (5.7%±0.7% (39 mmol/mol±8 mmol/mol), p=0.003). In addition, according to the American Diabetes Association (ADA) guidelines for diagnosis, there was a significant over-representation of subjects with suspected diabetes (23% and 14%) and pre-diabetes (47% and 46%) in the severe periodontitis group and mild/moderate periodontitis groups, respectively, compared with the control group (10% and 37%, p=0.010). Notably, 18.1% of patients with suspected new diabetes were found among subjects with severe periodontitis compared with 9.9% and 8.5% among subjects with mild/moderate periodontitis and controls, respectively (p=0.024).ConclusionsThe dental office, with particular focus on patients with severe periodontitis, proved to be a suitable location for screening for (pre)diabetes; a considerable number of suspected new diabetes cases were identified. The early diagnosis and treatment of (pre)diabetes help to prevent more severe complications and benefit the treatment of periodontitis.
Patient experience with discharge instructions in postdischarge recovery: a qualitative study
Authors: Horstman Molly J , Mills Whitney L , Herman Levi I , Cai Cecilia , Shelton George , Qdaisat Tareq , Berger David H , Naik Aanand D 
Published: February 2017

ObjectivesWe examined the role of discharge instructions in postoperative recovery for patients undergoing colorectal surgery and report themes related to patient perceptions of discharge instructions and postdischarge experience.DesignSemistructured interviews were conducted as part of a formative evaluation of a Project Re-Engineered Discharge intervention adapted for surgical patients.SettingMichael E. DeBakey VA Medical Center, a tertiary referral centre in Houston, Texas.ParticipantsTwelve patients undergoing elective colorectal surgery. Interviews were conducted at the two-week postoperative appointment.ResultsParticipants demonstrated understanding of the content in the discharge instructions. During the interviews, participants reported several positive roles for discharge instructions in their postdischarge care: a sense of security, a reminder of inhospital education, a living document and a source of empowerment. Despite these positive associations, participants reported that the instructions provided insufficient information to promote access to care that effectively addressed acute issues following discharge. Participants noted difficulty reaching providers after discharge, which resulted in the adoption of workarounds to overcome system barriers.ConclusionsDespite concerted efforts to provide patient-centred instructions, the discharge instructions did not provide enough context to effectively guide postdischarge interactions with the healthcare system. Insufficient information on how to access and communicate with the most appropriate personnel in the healthcare system is an important barrier to patients receiving high-quality postdischarge care. Tools and strategies from team training programmes, such as team strategies and tools to enhance performance and patient safety, could be adapted to include patients and provide them with structured methods for communicating with healthcare providers post discharge.
Waves of bone deposition on the rostrum of the pterosaur
Pteranodon
Authors: Bennett S. Christopher , Penkalski Paul 
Published: February 2017

Abstract

Four specimens of the pterosaur
Pteranodon
exhibit patterns of irregular alternating light and dark bands on the lateral surfaces of the upper jaw anterior to the nasoantorbital fenestra. Examinations reveal that the maxilla and premaxilla of
Pteranodon
consisted of two thin sheets of bone interconnected by regularly spaced septa with the spaces contained within presumably pneumatized, resulting in a structure analogous to modern honeycomb sandwich panels. The alternating light and dark bands resulted from waves of bone deposition moving anteriorly along the external surface of the lateral sheet of bone and laying down thin laminae of new bone while bone was simultaneously resorbed from the internal surface of the lateral sheet to maintain its thickness. The specimens that exhibit the bands were immature males and no banding was found in mature specimens or immature females. Therefore, the presence of the bands in immature males is interpreted as correlated with the enlargement and reshaping of the rostrum as males approached and attained sexual maturity.
A new pterosaur specimen from the Upper Tunbridge Wells Sand Formation (Cretaceous, Valanginian) of southern England and a review of
Lonchodectes sagittirostris
(Owen 1874)
Authors: Rigal Stanislas , Martill David M. , Sweetman Steven C. 
Published: February 2017

Abstract

A specimen of a pterodactyloid pterosaur from the Upper Tunbridge Wells Sand Formation (Early Cretaceous, Valanginian) of Bexhill, East Sussex, southern England is described. It comprises a small fragment of jaw with teeth, a partial vertebral column and associated incomplete wing bones. The juxtaposition of the bones suggests that the specimen was originally more complete and articulated. Its precise phylogenetic relationships are uncertain but it represents an indeterminate lonchodectid with affinities to
Lonchodectes sagittirostris
(Owen 1874) which is reviewed here, and may belong in
Lonchodraco
Rodrigues & Kellner 2013. This specimen is only the third record of pterosaurs from this formation.
A taxonomic revision of
Noripterus complicidens
and Asian members of the Dsungaripteridae
Authors: Hone D. W. E. , Jiang S. , Xu X. 
Published: February 2017

Abstract

After being inaccessible for a number of years, the holotype and other specimens of the dsungaripterid pterodactyloid pterosaur
Noripterus complicidens
are again available for study. Numerous taxa assigned to the Dsungaripteridae have been described since the erection of
Noripterus
, but with limited comparisons to this genus. Based on the information from Young's original material here we revise the taxonomic identity of
N. complicidens
and that of other Asian dsungaripterids. We conclude that
N. complicidens
is likely to be distinct from the material recovered from Mongolia and this latter material should be placed in a separate genus.
Tsunami simulations of mega-thrust earthquakes in the Nankai–Tonankai Trough (Japan) based on stochastic rupture scenarios
Authors: Goda Katsuichiro , Yasuda Tomohiro , Mai P. Martin , Maruyama Takuma , Mori Nobuhito 
Published: February 2017

Abstract
In this study, earthquake rupture models for future mega-thrust earthquakes in the Nankai–Tonankai subduction zone are developed by incorporating the main characteristics of inverted source models of the 2011 Tohoku earthquake. These scenario ruptures also account for key features of the national tsunami source model for the Nankai–Tonankai earthquake by the Central Disaster Management Council of the Japanese Government. The source models capture a wide range of realistic slip distributions and kinematic rupture processes, reflecting the current best understanding of what may happen due to a future mega-earthquake in the Nankai–Tonankai Trough, and therefore are useful for conducting probabilistic tsunami hazard and risk analysis. A large suite of scenario rupture models is then used to investigate the variability of tsunami effects in coastal areas, such as offshore tsunami wave heights and onshore inundation depths, due to realistic variations in source characteristics. Such investigations are particularly valuable for tsunami hazard mapping and evacuation planning in municipalities along the Nankai–Tonankai coast.
A longitudinal study of whole body, tissue, and cellular physiology in a mouse model of fibrosing NASH with high fidelity to the human condition
Authors: Krishnan Anuradha , Abdullah Tasduq Sheikh , Mounajjed Taofic , Hartono Stella , McConico Andrea , White Thomas , LeBrasseur Nathan , Lanza Ian , Nair Sreekumaran , Gores Gregory , Charlton Michael 
Published: February 2017

The sequence of events that lead to inflammation and fibrosing nonalcoholic steatohepatitis (NASH) is incompletely understood. Hence, we investigated the chronology of whole body, tissue, and cellular events that occur during the evolution of diet-induced NASH. Male C57Bl/6 mice were assigned to a fast-food (FF; high calorie, high cholesterol, high fructose) or standard-chow (SC) diet over a period of 36 wk. Liver histology, body composition, mitochondrial respiration, metabolic rate, gene expression, and hepatic lipid content were analyzed. Insulin resistance [homeostasis model assessment-insulin resistance (HOMA-IR)] increased 10-fold after 4 wk. Fibrosing NASH was fully established by 16 wk. Total hepatic lipids increased by 4 wk and remained two- to threefold increased throughout. Hepatic triglycerides declined from sixfold increase at 8 wk to threefold increase by 36 wk. In contrast, hepatic cholesterol levels steadily increased from baseline at 8 wk to twofold by 36 wk. The hepatic immune cell population altered over time with macrophages persisting beyond 16 wk. Mitochondrial oxygen flux rates of FF mice diet were uniformly lower with all the tested substrates (13–276 pmol·s−1·ml−1 per unit citrate synthase) than SC mice (17–394 pmol·s−1·ml−1 per unit citrate synthase) and was accompanied by decreased mitochondrial:nuclear gene copy number ratios after 4 wk. Metabolic rate was lower in FF mice. Mitochondrial glutathione was significantly decreased at 24 wk in FF mice. Expression of dismutases and catalase was also decreased in FF mice. The evolution of NASH in the FF diet-induced model is multiphasic, particularly in terms of hepatic lipid composition. Insulin resistance precedes hepatic inflammation and fibrosis. Mitochondrial dysfunction and depletion occur after the histological features of NASH are apparent. Collectively, these observations provide a unique overview of the sequence of changes that coevolve with the histological evolution of NASH. NEW & NOTEWORTHY This study demonstrates in a first of kind longitudinal analysis, the evolution of nonalcoholic steatohepatitis (NASH) on a fast-food diet-induced model. Key findings include 1) hepatic lipid composition changes in a multiphasic fashion as NASH evolves; 2) insulin resistance precedes hepatic inflammation and fibrosis, answering a longstanding chicken-and-egg question regarding the relationship of insulin resistance to liver histology in NASH; and 3) mitochondrial dysfunction and depletion occur after the histological features of NASH are apparent.
Impact of Disseminated Neuroblastoma Cells on the Identification of the Relapse-Seeding Clone
Authors: Abbasi M. Reza , Rifatbegovic Fikret , Brunner Clemens , Mann Georg , Ziegler Andrea , Pötschger Ulrike , Crazzolara Roman , Ussowicz Marek , Benesch Martin , Ebetsberger-Dachs Georg , Chan Godfrey C.F. , Jones Neil , Ladenstein Ruth , Ambros Inge M. , Ambros Peter F. 
Published: February 2017

Abstract
Purpose: Tumor relapse is the most frequent cause of death in stage 4 neuroblastomas. Since genomic information on the relapse precursor cells could guide targeted therapy, our aim was to find the most appropriate tissue for identifying relapse-seeding clones.
Experimental design: We analyzed 10 geographically and temporally separated samples of a single patient by SNP array and validated the data in 154 stage 4 patients.
Results: In the case study, aberrations unique to certain tissues and time points were evident besides concordant aberrations shared by all samples. Diagnostic bone marrow–derived disseminated tumor cells (DTCs) as well as the metastatic tumor and DTCs at relapse displayed a 1q deletion, not detected in any of the seven primary tumor samples. In the validation cohort, the frequency of 1q deletion was 17.8%, 10%, and 27.5% in the diagnostic DTCs, diagnostic tumors, and DTCs at relapse, respectively. This aberration was significantly associated with 19q and ATRX deletions. We observed a significant increased likelihood of an adverse event in the presence of 19q deletion in the diagnostic DTCs.
Conclusions: Different frequencies of 1q and 19q deletions in the primary tumors as compared with DTCs, their relatively high frequency at relapse, and their effect on event-free survival (19q deletion) indicate the relevance of analyzing diagnostic DTCs. Our data support the hypothesis of a branched clonal evolution and a parallel progression of primary and metastatic tumor cells. Therefore, searching for biomarkers to identify the relapse-seeding clone should involve diagnostic DTCs alongside the tumor tissue. Clin Cancer Res; 23(15); 4224–32. ©2017 AACR.