bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of the PB2 Mutation 627K on Highly Pathogenic H5N1 Avian Influenza Virus Is Dependent on the Virus Lineage
Authors: Long Jason S. , Howard Wendy A. , Núñez Alejandro , Moncorgé Olivier , Lycett Samantha , Banks Jill , Barclay Wendy S. 
Published: July 2013

ABSTRACT

Clade 2.2 Eurasian-lineage H5N1 highly pathogenic avian influenza viruses (HPAIVs) were first detected in Qinghai Lake, China, in 2005 and subsequently spread through Asia, Europe, and Africa. Importantly, these viruses carried a lysine at amino acid position 627 of the PB2 protein (PB2 627K), a known mammalian adaptation motif. Previous avian influenza virus isolates have carried glutamic acid in this position (PB2 627E), commonly described to restrict virus polymerase function in the mammalian host. We sought to examine the effect of PB2 627K on viral maintenance in the avian reservoir. Viruses constructed by reverse genetics were engineered to contain converse PB2 627K/E mutations in a Eurasian H5N1 virus (A/turkey/Turkey/5/2005 [Ty/05]) and, for comparison, a historical pre-Asian H5N1 HPAIV that naturally bears PB2 627E (A/turkey/England/50-92/1991 [50-92]). The 50-92 PB2 627K was genetically unstable during virus propagation, resulting in reversion to PB2 627E or the accumulation of the additional mutation PB2 628R and/or a synonymous mutation from an A to a G nucleotide at nucleotide position 1869 (PB2 A1869G). Intriguingly, PB2 628R and/or A1869G appeared to improve the genetic stability of 50-92 PB2 627K. However, the replication of 50-92 PB2 627K in conjunction with these stabilizing mutations was significantly restricted in experimentally infected chickens, where reversion to PB2 627E occurred. In contrast, no significant effects on viral fitness were observed for Ty/05 PB2 627E or 627K in
in vitro
or
in vivo
experiments. Our observations suggest that PB2 627K is supported in Eurasian-lineage viruses; in contrast, PB2 627K carries a significant fitness cost in the historical pre-Asian 50-92 virus.
Mutations in the Cytoplasmic Tail of Herpes Simplex Virus 1 gH Reduce the Fusogenicity of gB in Transfected Cells
Authors: Silverman Jessica L. , Heldwein Ekaterina E. 
Published: July 2013

ABSTRACT

Mutations within the cytoplasmic tail (cytotail) of herpes simplex virus 1 (HSV-1) gH were previously observed to suppress the syncytial phenotype of gB cytoplasmic domain mutant A855V in infected cells. Here, we examined the effects of gH cytotail mutations on virus-free cell-cell fusion in transfected cells to exclude the contributions of viral proteins other than gD, gH/gL, and gB. We show that a truncation at residue 832 coupled with the point mutation V831A within the cytotail of gH reduces fusion regardless of whether the wild type (WT) or a
syn
gB allele is present. We hypothesize that the gH cytotail mutations either reduce activation of gB by gH/gL or suppress the fusogenicity of gB through another, as yet unknown mechanism. The gB cytodomain and the gH cytotail do not interact
in vitro
, suggesting that mutations in the gH cytotail may instead affect the function of the gH/gL ectodomain. Nevertheless, we cannot exclude the possibility that the gB cytodomain and the gH cytotail interact in the context of full-length membrane-anchored proteins. The observed fusion suppression in transfected cells is less prominent than what was seen in infected cells, and we propose that gH cytotail mutations may additionally suppress syncytium formation in cells infected with
syn
HSV-1 by acting on other viral proteins, reinforcing the idea that fusion of HSV-infected cells is a complex phenomenon. Although fusion suppression by the gH cytotail mutant in transfected cells was evident when syncytia were visualized and counted, it was not detected by the luciferase assay, highlighting the differences between the two assays.
Does bony hip morphology affect the outcome of treatment for patients with adductor-related groin pain? Outcome 10 years after baseline assessment
Authors: Hölmich Per , Thorborg Kristian , Nyvold Per , Klit Jakob , Nielsen Michael B , Troelsen Anders 
Published: July 2013

BackgroundAdductor-related groin pain and bony morphology such as femoroacetabular impingement (FAI) or hip dysplasia can coexist clinically. A previous randomised controlled trial in which athletes with adductor-related groin pain underwent either passive treatment (PT) or active treatment (AT) showed good results in the AT group. The primary purpose of the present study was to evaluate if radiological signs of FAI or hip dysplasia seem to affect the clinical outcome, initially and at 8–12 years of follow-up.Methods47 patients (80%) were available for follow-up. The clinical result was assessed by a standardised clinical outcome combining patient-reported activity, symptoms and physical examination. Anterioposterior pelvic radiographs were obtained and the centre-edge angle of Wiberg, α angle, presence of a crossover sign and Tönnis grade of osteoarthritis were assessed by a blinded observer using a reliable protocol.ResultsNo significant between-group differences regarding the distribution of radiological morphologies were found. There was a decrease over time in clinical outcome in the AT group with α angles >55° compared to those with α angles <55° (p=0.047). In the AT group, there was no significant difference in the distribution of Tönnis grades between hips that had an unchanged or improved outcome compared with hips that had a worse outcome over time (p=0.145).ConclusionsNo evidence was found that bony hip morphology related to FAI or dysplasia prevents successful outcome of the exercise treatment programme with results lasting 8–12 years. The entity of adductor-related groin pain in physically active adults can be treated with AT even in the presence of morphological changes to the hip joint.
A cross-sectional study of Jamaican adolescents’ risk for type 2 diabetes and cardiovascular diseases
Authors: Barrett Sheila C , Huffman Fatma G , Johnson Paulette , Campa Adriana , Magnus Marcia , Ragoobirsingh Dalip 
Published: July 2013

ObjectivesTo compare obese versus non-obese Jamaican adolescents’ risk for type 2 diabetes (T2D) and cardiovascular diseases (CVDs); and to explore a suitable and economical method of screening for these risk factors in the school settings.DesignA descriptive cross-sectional study of adolescents’ risk for T2D and CVD. All the participants were examined at their respective schools.SettingJamaica, West Indies.Population276 Jamaican adolescents aged 14–19 years, randomly selected from grades 9 to 12 from 10 high schools on the island and included both boys and girls. All ethnicities on the island were represented.Main outcome measuresHigh fasting blood glucose, total cholesterol, glycated haemoglobin (HbA1c), blood pressure, body mass index (BMI), waist circumference, waist-to-hip ratio, family history of obesity, T2D and CVDs, low physical activity, and presence of Acanthosis Nigricans. All blood measures were analysed using the finger prick procedure.ResultsWaist circumference, waist-to-hip ratio, Acanthosis Nigricans, total cholesterol, family history of T2D and blood pressure were the strongest predictors of BMI (p=0.001). Over one-third of the participants were overweight. Jamaican adolescent females had a significantly higher number of risk factors and were less physically active than males (p<0.05). Over 80% of participants reported ≥3 risk factors for T2D and CVD. Participants with BMI ≥25 reported five or more risk factors. One-third of the overweight participants were classified with metabolic syndrome.ConclusionsJamaican adolescents are at risk of T2D and CVD. Family history of disease and anthropometric measures identified more participants at risk than did the blood measures. Jamaican adolescent females reported more risk factors for T2D and CVD as compared to males. Collection of this type of data was feasible within the school settings. All data were collected in 1 day per school. Intervention measures are needed to educate Jamaican adolescents to reduce overweight and subsequently the risk factors.
Long-term change in alcohol-consumption status and variations in fibrinogen levels: the coronary artery risk development in young adults (CARDIA) study
Authors: Okwuosa Tochi M , Klein Oana , Chan Cheeling , Schreiner Pamela , Liu Kiang , Green David 
Published: July 2013

ObjectiveTo examine long-term associations between change in alcohol-consumption status and cessation of alcohol use, and fibrinogen levels in a large, young, biracial cohort.DesignAnalysis of covariance models were used to analyse participants within the Coronary Artery Risk Development in Young Adults Study (CARDIA) cohort who had fibrinogen and alcohol use data at year 7 (1992–1993; ages 25–37) and year 20 examinations.Setting4 urban US cities.Patients2520 men and women within the CARDIA cohort.Main outcome measures13-year changes in alcohol use related to changes in fibrinogen.ResultsOver 13 years, mean fibrinogen increased by 71 vs 70 mg/dL (p=NS) in black men (BM) versus white men (WM), and 78 vs 68 mg/dL (p<0.05) in black women (BW) versus white women (WW), respectively. Compared with never-drinkers, there were smaller longitudinal increases in fibrinogen for BM, BW and WW (but a larger increase in WM) who became or stayed drinkers, after multivariable adjustment. For BM, WM and WW, fibrinogen increased the most among persons who quit drinking over 13 years (p<0.001 for WM (fibrinogen increase=86.5 (7.1) (mean (SE))), compared with never-drinkers (fibrinogen increase=53.1 (5.4)).ConclusionsIn this young cohort, compared with the participants who never drank, those who became/stayed drinkers had smaller increases, while those who quit drinking had the highest increase in fibrinogen over 13 years of follow-up. The results provide a novel insight into the mechanism for the established protective effect of moderate alcohol intake on cardiovascular disease outcomes.
Mortality following unemployment during an economic downturn: Swedish register-based cohort study
Authors: Montgomery Scott , Udumyan Ruzan , Magnuson Anders , Osika Walter , Sundin Per-Ola , Blane David 
Published: July 2013

ObjectiveTo investigate if unemployment during an economic downturn is associated with mortality, even among men with markers of better health (higher cognitive function scores and qualifications), and to assess whether the associations vary by age at unemployment.DesignLongitudinal register-based cohort study.SettingStudy entry was in 1990 and 2001 when Sweden was entering periods of significant economic contraction.ParticipantsA representative sample of men from the general population (n=234 782) born between 1952 and 1956 who participated in military conscription examinations. Men in receipt of disability or sickness benefit at study entry were excluded.Main outcome measureAll-cause mortality.ResultsUnemployment compared with employment in 1991 (ages 34–38 years) produced adjusted HRs (with 95% CIs) for all-cause mortality (3651 deaths) during follow-up to 2001 and after stratification by education of 2.35 (1.99 to 2.76) for compulsory education, 2.25 (1.97 to 2.58) for up to 3 years postcompulsory education and 1.90 (1.40 to 2.57) for more than 3 years postcompulsory education. When unemployment was compared with employment in 2001 (ages 45–49 years) with follow-up to 2010, the pattern of mortality risk (4271 deaths) stratified by education was reversed, producing adjusted HRs of 2.81 (2.47 to 3.21) for compulsory education, 2.87 (2.58 to 3.19) for up to 3 years postcompulsory education and 3.44 (2.78 to 4.25) for more than 3 years postcompulsory education. Interaction testing confirmed effect modification by age/period (p=0.003). The degree of gradient reversal was slightly less pronounced after stratification by cognitive function but produced a similar pattern of results (p=0.004).ConclusionsUnemployment at older ages is associated with greater mortality risk than at younger ages, with the greatest relative increase in risk among men with markers of better health, suggesting the greater vulnerability of all older workers to unemployment-associated exposures.
Haemolytic anaemia and acute pancreatitis associated with zinc toxicosis in a dog
Authors: Blundell R. , Adam F. 
Published: July 2013

We describe a case of zinc toxicity in a 14‐month‐old, female, neutered, Cavalier King Charles spaniel with a 48‐hour history of haematochezia, icterus and collapse. Regenerative anaemia with a packed‐cell volume of 7 per cent was seen. Prior to referral, radiography had revealed a gastric, metallic foreign body which was removed at exploratory laparotomy. On presentation, the dog was comatose, hypothermic and bradycardic – resuscitation was performed successfully, but the dog then displayed marked abdominal pain. The dog died 12 hours after presentation. At postmortem examination, the animal showed severe icterus. Both kidneys were diffusely dark red; the pancreas was diffusely pale and nodular. Histopathological examination revealed evidence of intravascular haemolysis with blood vessel lumens containing haemoglobin. The renal tubules also contained large amounts of intraluminal haemoglobin with haemoglobin crystals scattered throughout the cortex and medulla. The pancreas exhibited multifocal coagulative necrosis, surrounded by a neutrophil‐dominated inflammatory infiltrate. Zinc levels were markedly increased above the normal reference range in both liver and kidney. This report describes the clinical and pathological findings of a case of acute zinc toxicity in a dog following ingestion of a metallic object which resulted in marked haemolytic anaemia and acute pancreatitis.
Observational study of 14 cases of chronic pancreatitis in dogs
Authors: Watson P. J. , Archer J. , Roulois A. J. , Scase T. J. , Herrtage M. E. 
Published: July 2013

This study reports the clinical, clinicopathological and ultrasonographic findings from dogs with chronic pancreatitis (CP). Fourteen dogs with clinical signs consistent with CP and histological confirmation of the disease were evaluated. Abdominal ultrasound and clinical pathology results were recorded. Sensitivities of pancreatic enzymes for diagnosis of CP were calculated with two different cut‐off values. The mean age of affected dogs was 9.1 years. Spaniels were the most common breed with CP, representing seven of the 14 dogs in this study. CP was histologically severe in nine cases. Most dogs showed chronic low‐grade gastrointestinal signs and abdominal pain. Five dogs had exocrine pancreatic insufficiency and five dogs had diabetes mellitus. The sensitivity of elevated trypsin‐like immunoreactivity for CP was 17 per cent. The sensitivities of canine pancreatic lipase immunoreactivity, lipase and amylase for CP were 44 to 67 per cent or 14 to 28 per cent depending on the cut‐off value used. Cholesterol was elevated in 58 per cent of samples. Liver enzymes were often elevated. The pancreas appeared abnormal on 56 per cent of ultrasound examinations. Ten dogs had died by the end of the study period; only one case was due to CP.
Use of arterial blood gas analysis as a superior method for evaluating respiratory function in pet rabbits (Oryctolagus cuniculus)
Authors: Eatwell K. , Mancinelli E. , Hedley J. , Benato L. , Shaw D. J. , Self I. , Meredith A. 
Published: July 2013

A retrospective study compared invasive (arterial blood gas analysis) and non‐invasive (capnography and pulse oximetry) methods of monitoring respiratory function in conscious rabbits. Arterial samples from 50 healthy dwarf lop rabbits, presenting for routine surgical neutering, were analysed on a point‐of‐care blood gas analysis machine. Reference intervals were obtained for pH (7.35–7.54), PaCO2 (mm Hg) (25.29–40.37), PaO2 (mm Hg) (50.3–98.2), base excess (mmol/l) (6.7–6.5), HCO3 (mmol/l) (17.96–29.41), TCO2 (mmol/l) (18.9–30.5). SaO2 (per cent) (88.8–98.0), Na (mmol/l) (137.6–145.2), K (mmol/l) (3.28–4.87), iCal (mmol/l) (1.64–1.94), glucose (mmol/l) (6.23–10.53), haematocrit (per cent) (23.3–40.2) and haemoglobin (mg/dl) (7.91–13.63). Pulse oximetry (SPO2) and capnography (ETCO2) readings were taken concurrently. There was no statistically significant relationship between SPO2 and SaO2 with a mean difference between SPO2 and SaO2 of 8.22 per cent. There was a statistically significant relationship between ETCO2 vs PaCO2, but a wide range of ETCO2 values were observed for a given PaCO2. The mean difference between these was 16.16 mm Hg. The study has provided reference intervals for arterial blood gas analysis in rabbits and demonstrated that capnography and pulse oximetry readings should not be relied upon in conscious rabbits as a guide to ventilation and oxygenation.
Benzyl Isothiocyanate: Double Trouble for Breast Cancer Cells
Authors: Rao Chinthalapally V. 
Published: July 2013

Abstract
An inverse association between dietary intake of cruciferous vegetables and cancer risk has been established for different types of malignancies, including breast cancer. The anticarcinogenic effect of cruciferous vegetables has been attributed to chemicals with an isothiocyanate (ITC) functional moiety. Research over the past three decades has provided extensive preclinical evidence for the efficacy of various ITCs against cancer in preclinical models. Benzyl isothiocyanate (BITC) is one such compound with the ability to inhibit chemically induced cancer, oncogenic-driven tumor formation, and human tumor xenografts in rodent cancer models. Prior work also has established that BITC has the ability to influence carcinogen metabolism and signaling pathways relevant to tumor progression and invasion. In this issue, Kim and colleagues show that BITC inhibits breast cancer stem cell growth, both in vitro and in vivo, in association with suppression of the full-length receptor tyrosine kinase RON as well as its activated truncated form (sfRon), both of which seem to drive stemness in breast cancer cells. Overexpression of RON or sfRon prevented the BITC effect. These data complement prior work from this group showing elimination of mammary tumor cells via tumor cell apoptosis by BITC administration. The inhibition of breast cancer stem cells is observed at pharmacologic concentrations of BITC. This perspective briefly reviews epidemiologic evidence, preclinical efficacy data, and molecular and cellular mechanistic attributes of BITC. Critical issues relevant to clinical development of BITC are discussed briefly. Cancer Prev Res; 6(8); 760–3. ©2013 AACR.
Not Expecting the Unexpected: Diacylglycerol Kinase Alpha as a Cancer Target
Authors: Bhat Krishna P.L. , Aldape Kenneth 
Published: July 2013

Abstract
Summary: In this issue of Cancer Discovery, Dominguez and colleagues identify diacylglycerol kinase alpha (DGKα), an enzyme that converts the membrane lipid diacylglycerol to phosphatidic acid, as a central node upstream of mTOR and other oncogenic pathways. Importantly, targeting DGKα causes apoptosis in cancer cells and tumor growth inhibition in mice with no overt toxicity, implicating DGKα as a novel cancer-specific target. Cancer Discov; 3(7); 726–7. ©2013 AACR.
See related article by Dominguez et al., p. 782
Anticoagulation in patients with atrial fibrillation undergoing coronary stent implantation
Authors: Bernard Anne , Pellegrin Céline , Clementy Nicolas , Etienne Christophe Saint , Banerjee Amitava , Naudin Djedjiga , Angoulvant Denis , Fauchier Laurent 
Published: July 2013

SummaryIn patients with atrial fibrillation (AF) undergoing coronary stent implantation, the optimal antithrombotic strategy is unclear. We evaluated whether use of oral anticoagulation (OAC) was associated with any benefit in morbidity or mortality in patients with AF, high risk of thromboembolism (TE) (CHA2DS2-VASC score ≥2) and coronary stent implantation. Among 8,962 unselected patients with AF seen between 2000 and 2010, a total of 2,709 (30%) had coronary artery disease and 417/2,709 (15%) underwent stent implantation while having CHA2DS2-VASC score ≥2. During follow-up (median=650 days), all TE, bleeding episodes, and major adverse cardiac events (i.e. death, acute myocardial infarction, target lesion revascularisation) were recorded. At discharge, 97/417 patients (23%) received OAC, which was more likely to be prescribed in patients with permanent AF and in those treated for elective stent implantation. The incidence of outcome event rates was not significantly different in patients treated and those not treated with OAC. However, in multivariate analysis, the lack of OAC at discharge was independently associated with increased risk of death/stroke/systemic TE (relative risk [RR] =2.18, 95% confidence interval [CI] 1.02-4.67, p=0.04), with older age (RR =1.12, 1.04-1.20, p=0.003), heart failure (RR =3.26, 1.18-9.01, p=0.02), and history of stroke (RR =18.87, 3.11-111.11, p=0.001). In conclusion, in patients with AF and high thromboembolic risk after stent implantation, use of OAC was independently associated with decreased risk of subsequent death/stroke/systemic TE, suggesting that OAC should be systematically used in this patient population.
Validity of Negative High-Resolution Diffusion-Weighted Imaging in Transient Acute Cerebrovascular Events
Authors: Hotter Benjamin , Kufner Anna , Malzahn Uwe , Hohenhaus Marc , Jungehülsing Gerhard J. , Fiebach Jochen B. 
Published: July 2013

Background and Purpose—
A significant amount of strokes are reported to be diffusion-weighted imaging (DWI) negative in acute imaging. We attempted to quantify the rate of false-negative high-resolution (hr) DWI and to identify a valid screening tool to guide follow-up MRI to diagnose infarction initially not visible on hrDWI.

Methods—
An a priori–defined post hoc analysis of a prospective 3T MRI cohort of acute cerebrovascular events imaged within 24 hours of ictus. Basic demographics, risk factors, National Institute of Health Stroke Scale, and imaging parameters were recorded.

Results—
Of 151 patients with negative acute hrDWI, 63 received follow-up scans depicting infarction in 7 cases (11.1%). Persistence of clinical symptoms as established by National Institute of Health Stroke Scale on the following day was strongly associated with infarction on follow-up MRI (odds ratios, 17.5; 95% confidence interval, 2.83–108.12). Negative predictive value of follow-up National Institute of Health Stroke Scale was 0.96.

Conclusions—
Infarcts are frequently invisible on initial hrDWI, but we may well trust in negative hrDWI in completely transient cerebrovascular events.
La place de la coutume internationale en droit public français
Authors: Stirn Bernard 
Published: July 2013

Abstract
Bernard Stirn’s presentation examines the status of international custom in French public law. He notes that international custom may be considered as covered by the reference in the preamble of the Constitution to the rules of public international law. He underlines the increased effects of international custom in the French domestic legal order as enshrined in the latest developments of the case-law of the Conseil d’Etat. He stresses that whilst French administrative judges may set aside a law in the event of a conflict with the provisions of an international treaty, they do not possess a similar power in the case of a conflict with a rule of customary international law. He concludes by citing cases in which the French constitutional court has made reference to international custom.