bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pseudodominant inheritance pattern in a family with CMT2 caused by GDAP1 mutations
Authors: van Paassen Barbara W. , Bronk Marieke , Verhamme Camiel , van Ruissen Fred , Baas Frank , van Spaendonck‐Zwarts Karin Y. , de Visser Marianne 
Published: August 2017

AbstractWe report a family in which an autosomal dominantly inherited Charcot‐Marie‐Tooth (CMT) disease type 2 was suspected. The affected family members (proband, sister, father, and paternal aunt) showed intrafamilial clinical variability. The proband needed walking aids since adolescence because of generalized muscle weakness. The sister showed the same symptoms although to a lesser extent. The father and paternal aunt had foot deformity and atrophy of lower legs. A homozygous GDAP1 mutation was found in the proband and in the sister. Further testing showed compound heterozygous GDAP1 mutations in the father and paternal aunt. In this CMT2 family with a pseudodominant inheritance pattern DNA‐diagnostics revealed the presence of both homozygous and compound heterozygous GDAP1 mutations. We recommend including multiple family members in genetic studies on CMT families.
Survival and neurodevelopmental outcomes in extremely preterm infants 22–24 weeks of gestation born in Western Australia
Authors: Sharp Mary , French Noel , McMichael Judy , Campbell Catherine 
Published: August 2017

AimThe management of births at borderline viability continues to present dilemmas for health professionals and parents. The aim of the study was to review local outcomes of infants born between 22 and 24 weeks of gestation between 2004 and 2010 in Western Australia (WA) to aid perinatal counselling.MethodsSurvival data for the study were sourced retrospectively from the Neonatal Clinical Care Unit and Department of Health records of births in WA. Neurodevelopmental follow‐up outcomes were assessed using the most recent standardised assessment (Griffiths, Bayley‐III and Wechsler Preschool and Primary Scale of Intelligence, 3rd Ed) and medical examination of infants/children 12 months to 8 years from follow‐up clinic appointments.ResultsAt these gestations, 159 survivors represented 72% of neonatal intensive care unit admissions, 53% of WA live births and 26% of WA live and still births; 5% of live births survived at 22 weeks, 46% at 23 weeks and 77% at 24 weeks. Of the 14 outborn/retrieved infants, 4 survived (29%). At a median age of 59 months, disabilities were severe in 13% of children (22–23w = 19%; 24w = 11%). The median test quotient was 90. Moderate and severe cognitive disability was found in 16%, cerebral palsy was found in 7% (n = 11), and 55% of children were free from impairment as defined in this study.ConclusionAt these gestations, survival figures varied markedly with the chosen population denominator. Regional data are essential for valid population comparison. While many developmental difficulties occurred in these children, 78% were free from moderate or severe impairment at ages 3–5 years.
Effects of hydrocolloids as fat replacers on the physicochemical properties of produced Labneh
Authors: Saleh Mohammed , Al‐Baz Fahed , Al‐Ismail Khalid 
Published: August 2017

AbstractThis study was undertaken to investigate the effects of hydrocolloids when used as fat replacers on the physicochemical properties of Labneh. Four combination sets of carboxymethylcellulose, Arabic gum, carrageenan, and xanthan were used in a three factor mixture response surface methodology. Labneh water holding capacity (WHC), viscosity parameters, texture and sensory attributes were assessed. WHC played the critical role in affecting produced Labneh physical properties. Hydrocolloids influenced Labneh WHC in the following order; xanthan > Arabic gum > carrageenan > carboxymethylcellulose. Furthermore, xanthan showed an antagonistic effect with carboxymethylcellulose that lead to the decrease in WHC. Usage of 17% xanthan and 66% Arabic gum resulted in an increase in WHC to 98.6% which indicates a mixture response effect of hydrocolloids in affecting WHC of produced Labneh. The increase in carrageenan from 17% to 66% resulted in an increase in WHC from 62.7 to 70.7%. Consumer testing showed a superior Labneh sensory attributed using various hydrocolloids combinations compared to a control. Hydrocolloids were successfully used in Labneh as fat replacers. The developed reduced fat Labneh with its texture and sensory attributed that exceeded the full fat Labneh attributed can provide a solution to consumers with restricting fat diets.Practical applicationsCarbohydrate‐based fat replacers are of growing interest because of their physicochemical, sensorial properties, and health characteristics. The used hydrocolloids suggest plausible texture and sensory attributes solution in low or reduced fat content products including dairy products.
Adaptation of diet in a changed environment: Increased consumption of lobster krill Munida gregaria (Fabricius, 1793) by Argentine hake
Authors: Belleggia Mauro , Giberto Diego , Bremec Claudia 
Published: August 2017

AbstractA well‐replicated decadal‐term (2005–2014) stomach content data set was analysed in order to infer inter‐annual fluctuations in the diet of the Argentine hake, Merluccius hubbsi, an opportunistic predator in the San Jorge Gulf (SJG) ecosystem in the Southwest Atlantic. Ten research cruises were carried out each year during January from 2005 to 2014. A total of 18,461 specimens of Me. hubbsi was analysed, of which 6,777 (36.71%) contained food in their stomachs. The diet of Me. hubbsi changed markedly from 2011 onwards, with much greater consumption of the lobster krill Munida gregaria compared to the years before 2011. The frequency of occurrence (%F) of Mu. gregaria in the stomach contents of Argentine hake increased from the year 2009 onwards, most noticeably since 2011, and mostly over the southern region of the SJG. The main predators of Mu. gregaria in the SJG are two species of teleost fish (pink cusk eel, Genypterus blacodes, Argentine seabass, Acanthistius brasilianus) and three Rajidae skates (Zearaja chilensis, Psammobatis spp. and Sympterygia bonapartii), which exhibited decreased catches in the years analysed. The increased consumption of Mu. gregaria by Me. hubbsi, coupled with decreased trends in abundance of the main predators of the lobster krill during the last decade, indicate that top‐down trophic dynamic control occurs in the SJG ecosystem.
Evaluation of a smartphone nutrition and physical activity application to provide lifestyle advice to pregnant women: The SNAPP randomised trial
Authors: Dodd Jodie M. , Louise Jennie , Cramp Courtney , Grivell Rosalie M. , Moran Lisa J. , Deussen Andrea R. 
Published: August 2017

AbstractOur objective was to evaluate the impact of a smartphone application as an adjunct to face‐to‐face consultations in facilitating dietary and physical activity change among pregnant women. This multicentre, nested randomised trial involved pregnant women with a body mass index ≥18.5 kg/m2, with a singleton pregnancy between 10 and 20 weeks' gestation, and participating in 2 pregnancy nutrition‐based randomised trials across metropolitan Adelaide, South Australia. All women participating in the SNAPP trial received a comprehensive dietary, physical activity, and behavioural intervention, as part of the GRoW or OPTIMISE randomised trials. Women were subsequently randomised to either the “Lifestyle Advice Only Group,” where women received the above intervention, or the “Lifestyle Advice plus Smartphone Application Group,” where women were additionally provided access to the smartphone application. The primary outcome was healthy eating index (HEI) assessed by maternal food frequency questionnaire completed at trial entry, and 28 and 36 weeks' gestation. Analyses were performed using intention‐to‐treat principles, with statistical significance at p = .05. One hundred sixty‐two women participated: 77 allocated to the Lifestyle Advice plus Smartphone Application Group and 85 to the Lifestyle Advice Only Group. Mean difference in HEI score at 28 weeks of pregnancy was 0.01 (CI [−2.29, 2.62]) and at 36 weeks of pregnancy −1.16 (CI [−4.60, 2.28]). There was no significant additional benefit from the provision of the smartphone application in improving HEI score (p = .452). Although all women improved dietary quality across pregnancy, use of the smartphone application was poor. Our findings do not support addition of the smartphone application.
Addressing barriers to maternal nutrition in low‐ and middle‐income countries: A review of the evidence and programme implications
Authors: Kavle Justine A. , Landry Megan 
Published: August 2017

AbstractAdequate maternal nutrition during the “first 1,000 days” window is critical from conception through the first 6 months of life to improve nutritional status and reduce the risk of poor birth outcomes, such as low birthweight and preterm birth. Unfortunately, many programmes have targeted implementation and monitoring of nutrition interventions to infants and young children, rather than to women during pregnancy or post‐partum. A literature review was conducted to identify barriers to food choice and consumption during pregnancy and lactation and to examine how low‐ and middle‐income countries have addressed maternal nutrition in programmes. A literature review of peer‐reviewed and grey literature was conducted, and titles and abstracts reviewed by authors. Twenty‐three studies were included in this review. Barriers to adequate nutrition during pregnancy included cultural beliefs related to knowledge of quantity of food to eat during pregnancy, amount of weight to gain during pregnancy, and “eating down” during pregnancy for fear of delivering a large baby. Foods considered inappropriate for consumption during pregnancy or lactation contributed to food restriction. Drivers of food choice were influenced by food aversions, economic constraints, and household food availability. Counselling on maternal diet and weight gain during pregnancy was seldom carried out. Programming to support healthy maternal diet and gestational weight gain during pregnancy is scant. Tailored, culturally resonant nutrition education and counselling on diet during pregnancy and lactation and weight gain during pregnancy, as well as monitoring of progress in maternal nutrition, are areas of needed attention.
B cells require Type 1 interferon to produce alloantibodies to transfused KEL‐expressing red blood cells in mice
Authors: Gibb David R. , Liu Jingchun , Santhanakrishnan Manjula , Natarajan Prabitha , Madrid David J. , Patel Seema , Eisenbarth Stephanie C. , Tormey Christopher A. , Stowell Sean R. , Iwasaki Akiko , Hendrickson Jeanne E. 
Published: August 2017

BACKGROUNDAlloantibodies to red blood cell (RBC) antigens can cause significant hemolytic events. Prior studies have demonstrated that inflammatory stimuli in animal models and inflammatory states in humans, including autoimmunity and viremia, promote alloimmunization. However, molecular mechanisms underlying these findings are poorly understood. Given that Type 1 interferons (IFN‐α/β) regulate antiviral immunity and autoimmune pathology, the hypothesis that IFN‐α/β regulates RBC alloimmunization was tested in a murine model.STUDY DESIGN AND METHODSLeukoreduced murine RBCs expressing the human KEL glycoprotein were transfused into control mice (WT), mice lacking the unique IFN‐α/β receptor (IFNAR1–/–), or bone marrow chimeric mice lacking IFNAR1 on specific cell populations. Anti‐KEL IgG production, expressed as mean fluorescence intensity (MFI), and B‐cell differentiation were examined.RESULTSTransfused WT mice produced anti‐KEL IgG alloantibodies (peak response MFI, 50.4). However, the alloimmune response of IFNAR1–/– mice was almost completely abrogated (MFI, 4.2; p < 0.05). The response of bone marrow chimeric mice lacking IFNAR1 expression in all hematopoietic cells or specifically in B cells was also diminished (MFI, 3.8 and 5.4, respectively, compared to control chimeras, MFI, 65.6; p < 0.01). Accordingly, transfusion‐induced differentiation of IFNAR1–/– B cells into germinal center B cells and plasma cells was significantly reduced, compared to WT B cells.CONCLUSIONSThis study demonstrates that B cells require signaling from IFN‐α/β to produce alloantibodies to the human KEL glycoprotein in mice. These findings provide a potential mechanistic basis for inflammation‐induced alloimmunization. If these findings extend to human studies, patients with IFN‐α/β–associated conditions may have an elevated risk of alloimmunization and benefit from personalized transfusion protocols.
Variable Sensitivity in Molecular Detection of Zika Virus in European Expert Laboratories: External Quality Assessment, November 2016
Authors: Charrel Remi , Mögling Ramona , Pas Suzan , Papa Anna , Baronti Cecile , Koopmans Marion , Zeller Hervé , Leparc-Goffart Isabelle , Reusken Chantal B. 
Published: August 2017

ABSTRACT

Zika virus (ZIKV) infections are a significant public health concern. A strong capability for ZIKV detection is an absolute requirement for adequate preparedness and response strategies and individual patient care. The objective of this study was to assess and improve the capability of European expert laboratories for molecular testing for ZIKV through an external quality assessment (EQA) scheme. Laboratories were provided a panel of 12 samples which included negative samples, samples containing African- or Asian-lineage ZIKV at various concentrations (10
3
to 10
9
copies/ml), and samples containing dengue virus, yellow fever virus, or chikungunya virus. The results were analyzed on the basis of the outcomes of testing for the samples and the extraction and detection method used. Samples with a ZIKV RNA status scored correctly by >50% of the laboratories were designated the core sample. A total of 85 panel outcomes were submitted by 50 laboratories in 31 countries. The results designated all samples as core samples. Thirty-three percent (28/85) of the panel outcomes identified all samples. Analysis at the laboratory level showed that only 40% of the laboratories (20/50), representing 45% of the countries, scored sufficiently; i.e., they had at least one test operational that scored all core samples correctly. There is a need for improvement of the molecular detection of ZIKV in 60% of the participating laboratories. While the specificity of the tests was more robust, the results of the EQA showed large variation in test sensitivity. Improvements should focus on both nucleic acid extraction and ZIKV detection methods.
CD8
+
T Cell Immune Response in Immunocompetent Mice during Zika Virus Infection
Authors: Huang Huarong , Li Shihua , Zhang Yongli , Han Xiaojuan , Jia Baoqian , Liu Hongtao , Liu Dandan , Tan Shuguang , Wang Qihui , Bi Yuhai , Liu William J. , Hou Baidong , Gao George Fu , Zhang Fuping 
Published: August 2017

ABSTRACT

Zika virus (ZIKV) infection causees neurologic complications, including Guillain-Barré syndrome in adults and central nervous system (CNS) abnormalities in fetuses. We investigated the immune response, especially the CD8
+
T cell response in C57BL/6 (B6) wild-type (WT) mice, during ZIKV infection. We found that a robust CD8
+
T cell response was elicited, major histocompatibility complex class I-restricted CD8
+
T cell epitopes were identified, a tetramer that recognizes ZIKV-specific CD8
+
T cells was developed, and virus-specific memory CD8
+
T cells were generated in these mice. The CD8
+
T cells from these infected mice were functional, as evidenced by the fact that the adoptive transfer of ZIKV-specific CD8
+
T cells could prevent ZIKV infection in the CNS and was cross protective against dengue virus infection. Our findings provide comprehensive insight into immune responses against ZIKV and further demonstrate that WT mice could be a natural and easy-access model for evaluating immune responses to ZIKV infection.

IMPORTANCE
ZIKV infection has severe clinical consequences, including Guillain-Barré syndrome in adults, microcephaly, and congenital malformations in fetuses and newborn infants. Therefore, study of the immune response, especially the adaptive immune response to ZIKV infection, is important for understanding diseases caused by ZIKV infection. Here, we characterized the CD8
+
T cell immune response to ZIKV in a comprehensive manner and identified ZIKV epitopes. Using the identified immunodominant epitopes, we developed a tetramer that recognizes ZIKV-specific CD8
+
T cells
in vivo
, which simplified the detection and evaluation of ZIKV-specific immune responses. In addition, the finding that tetramer-positive memory CD8
+
T cell responses were generated and that CD8
+
T cells can traffic to a ZIKV-infected brain greatly enhances our understanding of ZIKV infection and provides important insights for ZIKV vaccine design.
Uncoupling of Protease
trans
-Cleavage and Helicase Activities in Pestivirus NS3
Authors: Zheng Fengwei , Lu Guoliang , Li Ling , Gong Peng , Pan Zishu 
Published: August 2017

ABSTRACT

The nonstructural protein NS3 from the
Flaviviridae
family is a multifunctional protein that contains an N-terminal protease and a C-terminal helicase, playing essential roles in viral polyprotein processing and genome replication. Here we report a full-length crystal structure of the classical swine fever virus (CSFV) NS3 in complex with its NS4A protease cofactor segment (PCS) at a 2.35-Å resolution. The structure reveals a previously unidentified ∼2,200-Å
2
intramolecular protease-helicase interface comprising three clusters of interactions, representing a “closed” global conformation related to the NS3-NS4A
cis
-cleavage event. Although this conformation is incompatible with protease
trans
-cleavage, it appears to be functionally important and beneficial to the helicase activity, as the mutations designed to perturb this conformation impaired both the helicase activities
in vitro
and virus production
in vivo
. Our work reveals important features of protease-helicase coordination in pestivirus NS3 and provides a key basis for how different conformational states may explicitly contribute to certain functions of this natural protease-helicase fusion protein.

IMPORTANCE
Many RNA viruses encode helicases to aid their RNA genome replication and transcription by unwinding structured RNA. Being naturally fused to a protease participating in viral polyprotein processing, the NS3 helicases encoded by the
Flaviviridae
family viruses are unique. Therefore, how these two enzyme modules coordinate in a single polypeptide is of particular interest. Here we report a previously unidentified conformation of pestivirus NS3 in complex with its NS4A protease cofactor segment (PCS). This conformational state is related to the protease
cis
-cleavage event and is optimal for the function of helicase. This work provides an important basis to understand how different enzymatic activities of NS3 may be achieved by the coordination between the protease and helicase through different conformational states.
Nipah and Hendra Virus Nucleoproteins Inhibit Nuclear Accumulation of Signal Transducer and Activator of Transcription 1 (STAT1) and STAT2 by Interfering with Their Complex Formation
Authors: Sugai Akihiro , Sato Hiroki , Takayama Ikuyo , Yoneda Misako , Kai Chieko 
Published: August 2017

ABSTRACT

Henipaviruses, such as Nipah (NiV) and Hendra (HeV) viruses, are highly pathogenic zoonotic agents within the
Paramyxoviridae
family. The phosphoprotein (P) gene products of the paramyxoviruses have been well characterized for their interferon (IFN) antagonist activity and their contribution to viral pathogenicity. In this study, we demonstrated that the nucleoprotein (N) of henipaviruses also prevents the host IFN signaling response. Reporter assays demonstrated that the NiV and HeV N proteins (NiV-N and HeV-N, respectively) dose-dependently suppressed both type I and type II IFN responses and that the inhibitory effect was mediated by their core domains. Additionally, NiV-N prevented the nuclear transport of signal transducer and activator of transcription 1 (STAT1) and STAT2. However, NiV-N did not associate with Impα5, Impβ1, or Ran, which are members of the nuclear transport system for STATs. Although P protein is known as a binding partner of N protein and actively retains N protein in the cytoplasm, the IFN antagonist activity of N protein was not abolished by the coexpression of P protein. This suggests that the IFN inhibition by N protein occurs in the cytoplasm. Furthermore, we demonstrated that the complex formation of STATs was hampered in the N protein-expressing cells. As a result, STAT nuclear accumulation was reduced, causing a subsequent downregulation of interferon-stimulated genes (ISGs) due to low promoter occupancy by STAT complexes. This novel route for preventing host IFN responses by henipavirus N proteins provides new insight into the pathogenesis of these viruses.

IMPORTANCE
Paramyxoviruses are well known for suppressing interferon (IFN)-mediated innate immunity with their phosphoprotein (P) gene products, and the henipaviruses also possess P, V, W, and C proteins for evading host antiviral responses. There are numerous studies providing evidence for the relationship between viral pathogenicity and antagonistic activities against IFN responses by P gene products. Meanwhile, little attention has been paid to the influence of nucleoprotein (N) on host innate immune responses. In this study, we demonstrated that both the NiV and HeV N proteins have antagonistic activity against the JAK/STAT signaling pathway by preventing the nucleocytoplasmic trafficking of STAT1 and STAT2. This inhibitory effect is due to an impairment of the ability of STATs to form complexes. These results provide new insight into the involvement of N protein in viral pathogenicity via its IFN antagonism.
A statewide evaluation of seven strategies to reduce opioid overdose in North Carolina
Authors: Alexandridis Apostolos A , McCort Agnieszka , Ringwalt Christopher L , Sachdeva Nidhi , Sanford Catherine , Marshall Stephen W , Mack Karin , Dasgupta Nabarun 
Published: August 2017

BackgroundIn response to increasing opioid overdoses, US prevention efforts have focused on prescriber education and supply, demand and harm reduction strategies. Limited evidence informs which interventions are effective. We evaluated Project Lazarus, a centralised statewide intervention designed to prevent opioid overdose.MethodsObservational intervention study of seven strategies. 74 of 100 North Carolina counties implemented the intervention. Dichotomous variables were constructed for each strategy by county-month. Exposure data were: process logs, surveys, addiction treatment interviews, prescription drug monitoring data. Outcomes were: unintentional and undetermined opioid overdose deaths, overdose-related emergency department (ED) visits. Interrupted time-series Poisson regression was used to estimate rates during preintervention (2009–2012) and intervention periods (2013–2014). Adjusted IRR controlled for prescriptions, county health status and time trends. Time-lagged regression models considered delayed impact (0–6 months).ResultsIn adjusted immediate-impact models, provider education was associated with lower overdose mortality (IRR 0.91; 95% CI 0.81 to 1.02) but little change in overdose-related ED visits. Policies to limit ED opioid dispensing were associated with lower mortality (IRR 0.97; 95% CI 0.87 to 1.07), but higher ED visits (IRR 1.06; 95% CI 1.01 to 1.12). Expansions of medication-assisted treatment (MAT) were associated with increased mortality (IRR 1.22; 95% CI 1.08 to 1.37) but lower ED visits in time-lagged models.ConclusionsProvider education related to pain management and addiction treatment, and ED policies limiting opioid dispensing showed modest immediate reductions in mortality. MAT expansions showed beneficial effects in reducing ED-related overdose visits in time-lagged models, despite an unexpected adverse association with mortality.