bluuebunny/crossref_metadata_2025_split huggingface dataset:
The molecular cross talk of the dystrophin–glycoprotein complex
Authors: Gawor Marta , Prószyński Tomasz J. 
Published: October 2017

AbstractThe proper function of skeletal muscles relies on their ability to process signals derived from motor neurons, transmit stimuli along the muscle fibers, contract, and regenerate efficiently after injury. The dystrophin–glycoprotein complex (DGC; also called the dystrophin‐associated protein complex) plays a central role in all of these processes. It acts as a transmembrane platform that anchors the extracellular matrix (ECM) to the intracellular cytoskeleton and makes muscle fibers more resistant to injury. The DGC also contributes to the transmission of contraction‐evoked force from the sarcomere to the ECM. The dysfunction of DGC‐associated proteins can lead to myopathies, including Duchenne's muscular dystrophy, manifested by progressive muscle damage and impairments in regeneration. The DGC also plays a pivotal role in the organization of neuromuscular junctions (NMJs), where it stabilizes postsynaptic machinery, including receptors for the neurotransmitter acetylcholine (AChRs). Here, we focus on the role of the DGC complex in NMJ and skeletal muscle physiology and discuss the novel components that are associated with the complex.
Diabetes training for community health workers on an American Indian reservation
Authors: Policicchio Judith M. , Dontje Katherine 
Published: October 2017

AbstractObjectivesTo improve the knowledge and skills of community health workers (CHWs) on an American Indian (AI) Reservation related to the management of diabetes to allow CHWs, with no prior formal diabetes education to work more effectively with individuals in the community with diabetes. Training was provided in six “face‐to‐face” sessions with the CHWs using the Centers for Disease Control and Prevention CHW Training Resource on Heart Disease and Stroke.Design and SampleThis is a quality improvement program guided by the Model for Improvement: Plan, Do, Study, Act and using a pre‐post evaluation design. Ten AI CHWs were recruited for the training.MeasuresKnowledge and attitudes, participation rates, and participant satisfaction were measured.ResultsKnowledge increased overall with largest changes in diabetes, depression and cholesterol. Diabetes attitudes were high and consistent with those found in caregivers who support patient‐centered care. Participants reported learning, liking the class, and finding the materials helpful.ConclusionThis QI program provided by a public health nurse improved CHW's knowledge of diabetes and the management of diabetes. Next steps include formalizing the Reservation's CHW training program, expanding this training to other AI Health Service areas, and measuring the impact of CHWs in the community.
Austerity or welfare state transformation? Examining the impact of economic crises on social regulation in Europe
Authors: Steinebach Yves , Knill Christoph , Jordana Jacint 
Published: October 2017

AbstractThis article provides an encompassing analysis of how economic crises affect social regulation. The analysis is based on an innovative dataset that covers policy output changes in 13 European countries over a period of 34 years (1980–2013) in the areas of pensions, unemployment, and child benefits. By performing a negative binomial regression analysis, we show that economic crises do matter for social policymaking. Our main empirical finding is that crises impinge on social regulation by opening a window of opportunity that facilitates the dismantling of social policy standards. Yet crisis‐induced policy dismantling is restricted to adjustments based on existing policy instruments. We do not find significant variation in policymaking patterns across different macroeconomic conditions for the more structural elements of social policy portfolios, such as the envisaged social policy targets or the policy instruments applied. This suggests that economic crises do not lead to a profound transformation of the welfare state but to austerity.
Long‐Term Reaction Characteristics of CO2–Water–Rock Interaction: Insight into the Potential Groundwater Contamination Risk from Underground CO2 Storage
Authors: Takaya Yutaro , Nakamura Kentaro , Kato Yasuhiro 
Published: October 2017

AbstractCO2 sequestration into saline aquifers is considered to be one of the most promising options for reducing industrial CO2 emissions to the atmosphere. However, there are still many uncertainties regarding the storage of CO2 in the subsurface because of a lack of knowledge about CO2–water–rock interaction within CO2 reservoirs and the potential risk of CO2 leakage. In this study, we construct a semi‐open type experimental system that can reproduce the interactions under conditions close to those of actual CO2 reservoirs. Using the system, we conduct CO2–water–rock interaction experiments for 8 months to monitor the long‐term reaction and the mobilization of harmful metal elements. Altered tuffaceous rock is used in the experiment because these tuffaceous rock formations (called “Green Tuff”) are a potential candidate for CO2 storage in Japan. The results show that the major‐element water composition will converge to the point where host rock dissolution and secondary mineral precipitation are balanced; then, the interaction will proceed under a certain groundwater composition. In addition, we found that groundwater contamination by some metal elements (Ni, Ba, and Mn) may reach unsafe levels for drinking water as a result of CO2‐water–rock interaction.
On a Generality Condition in Proof‐Theoretic Semantics
Authors: Dicher Bogdan 
Published: October 2017

AbstractIn the recent literature on proof‐theoretic semantics, there is mention of a generality condition on defining rules. According to this condition, the schematic formulation of the defining rules must be maximally general, in the sense that no restrictions should be placed on the contexts of these rules. In particular, context variables must always be present in the schematic rules and they should range over arbitrary collections of formulae. I argue against imposing such a condition, by showing that it has undesirable results and that it is ill‐supported by the arguments brought in its favour.
Demographic and epidemiologic characterization of transfusion recipients from four US regions: evidence from the REDS‐III recipient database
Authors: Karafin Matthew S. , Bruhn Roberta , Westlake Matt , Sullivan Marian T. , Bialkowski Walter , Edgren Gustaf , Roubinian Nareg H. , Hauser Ronald G. , Kor Daryl J. , Fleischmann Debra , Gottschall Jerome L. , Murphy Edward L. , Triulzi Darrell J. ,   for the National Heart, Lung, and Blood Institute Recipient Epidemiology and Donor Evaluation Study‐III (REDS‐III)
Published: October 2017

BACKGROUNDBlood transfusion is one of the most common medical procedures during hospitalization in the United States. To understand the benefits of transfusion while mitigating potential risks, a multicenter database containing detailed information on transfusion incidence and recipient outcomes would facilitate research.STUDY DESIGN AND METHODSThe Recipient Epidemiology and Donor Evaluation Study‐III (REDS‐III) program has developed a comprehensive transfusion recipient database utilizing data from hospital electronic health records at 12 participating hospitals in four geographic regions. Inpatient and outpatient data on transfusion recipients from January 1, 2013 to December 31, 2014 included patient age, sex, ethnicity, primary diagnosis, type of blood product provided, issue location, pretransfusion and post‐transfusion hemoglobin (Hgb), and hospital outcomes. Transfusion incidence per encounter was calculated by blood product and various patient characteristics.RESULTSDuring the 2‐year study period, 80,362 (12.5%) inpatient encounters involved transfusion. Among inpatients, the most commonly transfused blood products were red blood cells (RBCs; 10.9% of encounters), followed by platelets (3.2%) and plasma (2.9%). Among patients who received transfusions, the median number of RBC units was one, the pretransfusion Hgb level was 7.6 g/dL, and the Hgb increment per unit was 1.4 g/dL. Encounter mortality increased with patient age, the number of units transfused, and the use of platelet or plasma products. The most commonly reported transfusion reaction was febrile nonhemolytic.CONCLUSIONThe database contains comprehensive data regarding transfusion use and patient outcomes. The current report describes an evaluation of the first 2 years of a planned, 4‐year, linked blood donor‐component‐recipient database, which represents a critical new resource for transfusion medicine researchers.
Subcutaneous administration of ciclosporin in 11 allergic cats – a pilot open‐label uncontrolled clinical trial
Authors: Koch Sandra N. , Torres Sheila M. F. , Diaz Sandra , Gilbert Sophie , Rendahl Aaron 
Published: October 2017

BackgroundOral ciclosporin has been reported to be efficacious for feline inflammatory skin diseases; however, cats are often difficult to medicate orally.Hypothesis/ObjectiveTo evaluate the efficacy and tolerability of subcutaneous ciclosporin administered to cats with allergic skin disease.AnimalsEleven client‐owned cats with nonseasonal clinical signs.MethodsProspective open label trial. Ciclosporin 50 mg/mL solution for injection (Sandimune®, Novartis; NJ, USA) was administered subcutaneously for 60 days with initial doses ranging from 2.5 mg/kg once daily (one cat) to every other day (five cats) and 5 mg/kg once daily (four cats) to every other day (one cat). Dosages were adjusted monthly if needed based on clinical response. Clinical response was assessed using a modified FeDESI (feline Dermatitis Extent and Severity Index) and PVAS (pruritus Visual Analog Scale) between days (D) 0, 30 and 60.ResultsSix cats completed the study and four of five cats withdrawn from the study were included in an intention‐to‐treat analysis. There was significant decrease in FeDESI and PVAS scores between D0 and D30, D0 and D60 and D30 and D60 (P < 0.05) in all ten cats.Conclusions and clinical importanceCiclosporin administered subcutaneously at initial doses of 2.5‐5 mg/kg, once daily to alternate days, appears to be an efficacious therapy for feline allergic dermatitis and may be an alternative therapy for cats that cannot be treated orally. Randomized and controlled long term studies which include a larger number of cats are needed to confirm these findings.
Towards bedside washing of stored red blood cells: a prototype of a simple apparatus based on microscale sedimentation in normal gravity
Authors: Khanal G. , Huynh R. A. , Torabian K. , Xia H. , Vörös E. , Shevkoplyas S. S. 
Published: October 2017

Background and ObjectivesInfusion of by‐products of red blood cell (RBC) storage‐induced degradation as well as of the residual plasma proteins and the anticoagulant‐preservative solution contained in units of stored blood serve no therapeutic purpose and may be harmful to some patients. Here, we describe a prototype of a gravity‐driven system for bedside washing of stored RBCs.Materials and MethodsStored RBCs were diluted to 10% haematocrit (Hct) with normal saline, matching the conventional washing procedure. The dilute RBC suspensions were passed through a column of coiled tubing to allow RBC sedimentation in normal gravity, thus separating them from the washing solution. Washed RBCs were collected using bifurcations located along the tubing. Washing efficiency was quantified by measuring Hct, morphology, deformability, free haemoglobin and total‐free protein.ResultsThe gravity‐driven washing system operating at 0·5 ml/min produced washed RBCs with final Hct of 36·7 ± 3·4% (32·3–41·2%, n = 10) and waste Hct of 3·4 ± 0·7% (2·4–4·3%, n = 10), while removing 80% of free haemoglobin and 90% of total‐free protein. Washing improved the ability of stored RBCs to perfuse an artificial microvascular network by 20%. The efficiency of washing performed using the gravity‐driven system was not significantly different than that of conventional centrifugation.ConclusionsThis proof‐of‐concept study demonstrates the feasibility of washing stored RBCs using a simple, disposable system with efficiency comparable to that of conventional centrifugation, and thus represents a significant first step towards enabling low‐cost washing of stored blood at bedside.
Synthetic liver function is detectable in transgenic porcine livers perfused with human blood
Authors: Cimeno Arielle , French Beth M. , Powell Jessica M. , Phelps Carol , Ayares David , O'Neill Natalie A. , Laird Christopher T. , Pierson Richard N. , Azimzadeh Agnes M. , Barth Rolf N. , LaMattina John C. 
Published: October 2017

AbstractIn addition to immune barriers, molecular incompatibilities between species are predicted to limit pig liver survival in primate xenotransplantation models. Assessment and measurement of synthetic function of genetically modified porcine livers after ex vivo perfusion with human blood have not previously been described. Eight porcine livers from α1,3‐galactosyl transferase knockout and human membrane cofactor (GalTKO.hCD46), six livers from GalTKO.hCD46 and N‐glycolylneuraminic acid knockout (GalTKO.hCD46.Neu5GcKO), and six livers from GalTKO.hCD46 with humanized decay‐accelerating factor (hCD55), endothelial protein C receptor (hEPCR), tissue factor pathway inhibitor (hTFPI), and integrin‐associated protein (hCD47) (GalTKO.hCD46.hCD55.hEPCR.hTFPI.hCD47) pigs were perfused with human blood under physiologic conditions. Timed blood samples were tested for liver enzymes and for pig‐specific albumin production via Western blot. Porcine albumin levels increased with time in all experiments. By densitometry, GalTKO.hCD46.Neu5GcKO livers had the highest albumin levels, measured both as total produced, and when controlled for perfusion duration, compared to GalTKO.hCD46 (P = .068) and GalTKO.hCD46.hCD55.hEPCR.hTFPI.hCD47 livers (P = .04). Porcine livers perfused with human blood demonstrated the synthetic ability to produce albumin in all cases. GalTKO.hCD46.Neu5GcKO pig livers demonstrated the most robust albumin production. This suggests that the Neu5GcKO phenotype provides a protective effect on the graft due to decreased human antibody recognition and graft injury.
Genotype 2 Strains of Porcine Reproductive and Respiratory Syndrome Virus Dysregulate Alveolar Macrophage Cytokine Production via the Unfolded Protein Response
Authors: Chen Wei-Yu , Schniztlein William M. , Calzada-Nova Gabriela , Zuckermann Federico A. 
Published: October 2017

ABSTRACT
Porcine reproductive and respiratory syndrome virus (PRRSV) infects alveolar macrophages (AMϕ), causing dysregulated alpha interferon (IFN-α) and tumor necrosis factor alpha (TNF-α) production through a mechanism(s) yet to be resolved. Here, we show that AMϕ infected with PRRSV secreted a reduced quantity of IFN-α following exposure of the cell to synthetic double-stranded RNA (dsRNA). This reduction did not correlate with reduced IFNA1 gene transcription. Rather, it coincided with two events that occurred late during infection and that were indicative of translational attenuation, specifically, the activation of eukaryotic translation initiation factor 2α (eIF2α) and the appearance of stress granules. Notably, the typical rapid production of TNF-α by AMϕ exposed to lipopolysaccharide (LPS) was suppressed or enhanced by PRRSV, depending on when the LPS exposure occurred after virus infection. If exposure was delayed until 6 h postinfection (hpi) so that the development of the cytokine response coincided with the time in which phosphorylation of eIF2α by the stress sensor PERK (protein kinase RNA [PKR]-like ER kinase) occurred, inhibition of TNF-α production was observed. However, if LPS exposure occurred at 2 hpi, prior to a detectable onset of eIF2α phosphorylation, a synergistic response was observed due to the earlier NF-κB activation via the stress sensor IRE1α (inositol-requiring kinase 1α). These results suggest that the asynchronous actions of two branches of the unfolded protein response (UPR), namely, IRE1α, and PERK, activated by ER stress resulting from the virus infection, are associated with enhancement or suppression of TNF-α production, respectively.

IMPORTANCE
The activation of AMϕ is controlled by the microenvironment to deter excessive proinflammatory cytokine responses to microbes that could impair lung function. However, viral pneumonias frequently become complicated by secondary bacterial infections, triggering severe inflammation, lung dysfunction, and death. Although dysregulated cytokine production is considered an integral component of the exacerbated inflammatory response in viral-bacterial coinfections, the mechanism responsible for this event is unknown. Here, we show that PRRSV replication in porcine AMϕ triggers activation of the IRE1α branch of the UPR, which causes a synergistic TNF-α response to LPS exposure. Thus, the severe pneumonias typically observed in pigs afflicted with PRRSV-bacterial coinfections could result from dysregulated, overly robust TNF-α production in response to opportunistic pathogens that is not commensurate with the typical restrained reaction by uninfected AMϕ. This notion could help in the design of therapies to mitigate the severity of viral and bacterial coinfections.
NS3 from Hepatitis C Virus Strain JFH-1 Is an Unusually Robust Helicase That Is Primed To Bind and Unwind Viral RNA
Authors: Zhou Ting , Ren Xiaoming , Adams Rebecca L. , Pyle Anna Marie 
Published: October 2017

ABSTRACT
Hepatitis C viruses (HCV) encode a helicase enzyme that is essential for viral replication and assembly (nonstructural protein 3 [NS3]). This helicase has become the focus of extensive basic research on the general helicase mechanism, and it is also of interest as a novel drug target. Despite the importance of this protein, mechanistic work on NS3 has been conducted almost exclusively on variants from HCV genotype 1. Our understanding of NS3 from the highly active HCV strains that are used to study HCV genetics and mechanism in cell culture (such as JFH-1) is lacking. We therefore set out to determine whether NS3 from the replicatively efficient genotype 2a strain JFH-1 displays novel functional or structural properties. Using biochemical assays for RNA binding and duplex unwinding, we show that JFH-1 NS3 binds RNA much more rapidly than the previously studied NS3 variants from genotype 1b. Unlike NS3 variants from other genotypes, JFH-1 NS3 binds RNA with high affinity in a functionally active form that is capable of immediately unwinding RNA duplexes without undergoing rate-limiting conformational changes that precede activation. Unlike other superfamily 2 (SF2) helicases, JFH-1 NS3 does not require long 3′ overhangs, and it unwinds duplexes that are flanked by only a few nucleotides, as in the folded HCV genome. To understand the physical basis for this, we solved the crystal structure of JFH-1 NS3, revealing a novel conformation that contains an open, positively charged RNA binding cleft that is primed for productive interaction with RNA targets, potentially explaining robust replication by HCV JFH-1.

IMPORTANCE
Genotypes of HCV are as divergent as different types of flavivirus, and yet mechanistic features of HCV variants are presumed to be held in common. One of the most well-studied components of the HCV replication complex is a helicase known as nonstructural protein 3 (NS3). We set out to determine whether this important mechanical component possesses biochemical and structural properties that differ between common strains such as those of genotype 1b and a strain of HCV that replicates with exceptional efficiency (JFH-1, classified as genotype 2a). Indeed, unlike the inefficient genotype 1b NS3, which has been well studied, JFH-1 NS3 is a superhelicase with strong RNA affinity and high unwinding efficiency on a broad range of targets. Crystallographic analysis reveals architectural features that promote enhanced biochemical activity of JFH-1 NS3. These findings show that even within a single family of viruses, drift in sequence can result in the acquisition of radically new functional properties that enhance viral fitness.
Maternal but Not Infant Anti-HIV-1 Neutralizing Antibody Response Associates with Enhanced Transmission and Infant Morbidity
Authors: Ghulam-Smith Melissa , Olson Alex , White Laura F. , Chasela Charles S. , Ellington Sascha R. , Kourtis Athena P. , Jamieson Denise J. , Tegha Gerald , van der Horst Charles M. , Sagar Manish 
Published: October 2017

ABSTRACTA significant number of infants acquire HIV-1 through their infected mother’s breast milk, primarily due to limited access to antiretrovirals. Passive immunization with neutralizing antibodies (nAbs) may prevent this transmission. Previous studies, however, have generated conflicting results about the ability of nAbs to halt mother-to-child transmission (MTCT) and their impact on infant outcomes. This study compared plasma neutralizing activity in exposed infants and the infected mothers (n =63) against heterologous HIV-1 variants and the quasispecies present in the mother. HIV-exposed uninfected infants (HEU) (n =42), compared to those that eventually acquired infection (n =21), did not possess higher nAb responses against heterologous envelopes (P= 0.46) or their mothers’ variants (P= 0.45). Transmitting compared to nontransmitting mothers, however, had significantly higher plasma neutralizing activity against heterologous envelopes (P= 0.03), although these two groups did not have significant differences in their ability to neutralize autologous strains (P= 0.39). Furthermore, infants born to mothers with greater neutralizing breadth and potency were significantly more likely to have a serious adverse event (P= 0.03). These results imply that preexisting anti-HIV-1 neutralizing activity does not prevent breast milk transmission. Additionally, high maternal neutralizing breadth and potency may adversely influence both the frequency of breast milk transmission and subsequent infant morbidity.IMPORTANCEPassive immunization trials are under way to understand if preexisting antibodies can decrease mother-to-child HIV-1 transmission and improve infant outcomes. We examined the influence of preexisting maternal and infant neutralizing activity on transmission and infant morbidity in a breastfeeding mother-infant cohort. Neutralization was examined against both the exposure strains circulating in the infected mothers and a standardized reference panel previously used to estimate breadth. HIV-exposed uninfected infants did not possess a broader and more potent response against both the exposure and heterologous strains compared to infants that acquired infection. Transmitting, compared to nontransmitting, mothers had significantly higher neutralization breadth and potency but similar responses against autologous variants. Infants born to mothers with higher neutralization responses were more likely to have a serious adverse event. Our results suggest that preexisting antibodies do not protect against breast milk HIV-1 acquisition and may have negative consequences for the baby.