bluuebunny/crossref_metadata_2025_split huggingface dataset:
The genetic profile of Leber congenital amaurosis in an Australian cohort
Authors: Thompson Jennifer A. , De Roach John N. , McLaren Terri L. , Montgomery Hannah E. , Hoffmann Ling H. , Campbell Isabella R. , Chen Fred K. , Mackey David A. , Lamey Tina M. 
Published: August 2017

AbstractBackgroundLeber congenital amaurosis (LCA) is a severe visual impairment responsible for infantile blindness, representing ~5% of all inherited retinal dystrophies. LCA encompasses a group of heterogeneous disorders, with 24 genes currently implicated in pathogenesis. Such clinical and genetic heterogeneity poses great challenges for treatment, with personalized therapies anticipated to be the best treatment candidates. Unraveling the individual genetic etiology of disease is a prerequisite for personalized therapies, and could identify potential treatment candidates, inform patient management, and discriminate syndromic forms of disease.MethodsWe have genetically analyzed 45 affected and 82 unaffected individuals from 34 unrelated LCA pedigrees using predominantly next‐generation sequencing and Array CGH technology.ResultsWe present the molecular findings for an Australian LCA cohort, sourced from the Australian Inherited Retinal Disease Registry & DNA Bank. CEP290 and GUCY2D mutations, each represent 19% of unrelated LCA cases, followed by NMNAT1 (12%). Genetic subtypes were consistent with other reports, and were resolved in 90% of this cohort.ConclusionThe high resolution rate achieved, equivalent to recent findings using whole exome/genome sequencing, reflects the progression from hypothesis (LCA Panel) to non‐hypothesis (RD Panel) testing and, coupled with Array CGH analysis, is a highly effective first‐tier test for LCA.
Compound heterozygous CASQ2 mutations and long‐term course of catecholaminergic polymorphic ventricular tachycardia
Authors: Josephs Katherine , Patel Kunjan , Janson Christopher M. , Montagna Cristina , McDonald Thomas V. 
Published: August 2017

AbstractBackgroundCatecholaminergic polymorphic ventricular tachycardia (CPVT) is a potentially lethal inherited cardiac disorder characterized by episodic ventricular tachycardia during adrenergic stimulation. It is associated with significant morbidity and mortality. Knowledge of the underlying genetic cause, pathogenesis, and the natural history of the disease remains incomplete. Approximately 50% of CPVT cases are caused by dominant mutations in the cardiac ryanodine receptor (RYR2) gene, <5% of cases are accounted for by recessive mutations in cardiac calsequestrin (CASQ2) or Triadin (TRDN).MethodsWe report a family with two CASQ2 gene mutations. A research‐based next‐generation sequencing (NGS) initiative was used in a patient with a severe CPVT phenotype and her clinically unaffected son. Reverse transcription polymerase chain reaction (RT‐PCR) from platelet RNA was used to assess the consequences of predicted splice variants.ResultsNGS revealed that the proband carried a novel c.199C>T (p.Gln67*) mutation and a previously reported splice site mutation c.532+1G>A in CASQ2. Her son is a heterozygous carrier of the c.199C>T (p.Gln67*) mutation alone and the proband was compound heterozygous at CASQ2. RNA analysis demonstrated that the splice site mutation results in the retention of intron 3 with no full‐length CASQ2 mRNA.ConclusionThis study describes a novel CPVT genotype and further characterizes the effect of a previously reported CASQ2 splice site mutation. The long‐term follow‐up of 23 years since first symptom provides additional insight into the natural history of CASQ2‐associated CPVT.
A Lagrangian gradient smoothing method for solid‐flow problems using simplicial mesh
Authors: Mao Zirui , Liu G. R. 
Published: August 2017

SummaryA novel Lagrangian gradient smoothing method (L‐GSM) is developed to solve “solid‐flow” (flow media with material strength) problems governed by Lagrangian form of Navier‐Stokes equations. It is a particle‐like method, similar to the smoothed particle hydrodynamics (SPH) method but without the so‐called tensile instability that exists in the SPH since its birth. The L‐GSM uses gradient smoothing technique to approximate the gradient of the field variables, based on the standard GSM that was found working well with Euler grids for general fluids. The Delaunay triangulation algorithm is adopted to update the connectivity of the particles, so that supporting neighboring particles can be determined for accurate gradient approximations. Special techniques are also devised for treatments of 3 types of boundaries: no‐slip solid boundary, free‐surface boundary, and periodical boundary. An advanced GSM operation for better consistency condition is then developed. Tensile stability condition of L‐GSM is investigated through the von Neumann stability analysis as well as numerical tests. The proposed L‐GSM is validated by using benchmarking examples of incompressible flows, including the Couette flow, Poiseuille flow, and 2D shear‐driven cavity. It is then applied to solve a practical problem of solid flows: the natural failure process of soil and the resultant soil flows. The numerical results are compared with theoretical solutions, experimental data, and other numerical results by SPH and FDM to evaluate further L‐GSM performance. It shows that the L‐GSM scheme can give a very accurate result for all these examples. Both the theoretical analysis and the numerical testing results demonstrate that the proposed L‐GSM approach restores first‐order accuracy unconditionally and does not suffer from the tensile instability. It is also shown that the L‐GSM is much more computational efficient compared with SPH, especially when a large number of particles are employed in simulation.
Pharmacoepidemiology of testosterone: Curbing off‐label prescribing
Authors: Handelsman David J. 
Published: August 2017

AbstractObjectivesTo estimate the impact of the first year of new Pharmaceutical Benefits Scheme (PBS) prescribing criteria that dictate eligibility for national health scheme subsidy of testosterone prescribing.DesignAnalysis of cumulative PBS data.SettingRetrospective analysis of testosterone prescribing from PBS data.ParticipantsNilMain outcome measuresPBS expenditure analysed by total expenditure, by state, and by product type as well as the age, indication, and prescriber type for new testosterone treatment.ResultsTotal PBS expenditure continued to exceed $20 million in 2014 before declining from 2015 with changes that were uniform by state and product type. Prior to 2015, over 80% were for men aged over 40 years of age for low circulating testosterone in the absence of reproductive system disorders (“Low T”) initiated by GPs. From 2015, these features were markedly reduced without changing the numbers of new prescriptions for pathological reproductive disorders or specialist initiations.ConclusionsThe short‐term impact of 2015 PBS criteria showed highly effective and well‐targeted curbing of off‐label testosterone prescribing. The findings indicate that the main driver for the recent upsurge in testosterone prescribing was treatment of middle‐aged men for “Low T” initiated by GPs.
Why do oncologists hide the truth? Disclosure of cancer diagnoses to patients in China: A multisource assessment using mixed methods
Authors: Gan Yiqun , Zheng Lei , Yu Nancy Xiaonan , Zhou Guangyu , Miao Miao , Lu Qian 
Published: August 2017

AbstractObjectiveIn the United States and most European countries, cancer diagnoses are disclosed to patients. In China, however, the trend toward full disclosure has progressed slowly. The present study aimed to explore attitudes toward truth‐telling practice among physicians, patients, patients' family members, and the general population, and reasons for nondisclosure.MethodsWe administered a short survey to 212 physicians, 143 patients with cancer, 413 family members of patients with cancer, and 1415 members of the general population. A MANOVA was performed to examine group differences in attitudes toward cancer disclosure. In addition, we interviewed 20 oncologists. Interview data were analyzed using NVivo10. After the interview, we administered another short survey to 143 patients with cancer.ResultsQuantitative data indicated that physicians were the least, and patients the most, in favor of disclosure. Qualitative data among physicians and follow‐up surveys among cancer patients revealed 5 reasons for the concealment of cancer diagnoses by physicians, including lack of awareness of patients' right to knowledge, cultural influences, insufficient medical resources and training, families' financial concerns, and the need to protect doctors from violence.ConclusionThere is a discrepancy between the needs of patients and those in medical practice. These results deepen our understanding regarding the reasons for oncologists' attitudes toward nondisclosure.
Gene flow from single and stacked herbicide‐resistant rice (Oryza sativa): modeling occurrence of multiple herbicide‐resistant weedy rice
Authors: Dauer Joseph , Hulting Andrew , Carlson Dale , Mankin Luke , Harden John , Mallory‐Smith Carol 
Published: August 2017

AbstractBACKGROUNDProvisia™ rice (PV), a non‐genetically engineered (GE) quizalofop‐resistant rice, will provide growers with an additional option for weed management to use in conjunction with Clearfield® rice (CL) production. Modeling compared the impact of stacking resistance traits versus single traits in rice on introgression of the resistance trait to weedy rice (also called red rice). Common weed management practices were applied to 2‐, 3‐ and 4‐year crop rotations, and resistant and multiple‐resistant weedy rice seeds, seedlings and mature plants were tracked for 15 years.RESULTSTwo‐year crop rotations resulted in resistant weedy rice after 2 years with abundant populations (exceeding 0.4 weedy rice plants m–2) occurring after 7 years. When stacked trait rice was rotated with soybeans in a 3‐year rotation and with soybeans and CL in a 4‐year rotation, multiple‐resistance occurred after 2–5 years with abundant populations present in 4–9 years. When CL rice, PV rice, and soybeans were used in 3‐ and 4‐year rotations, the median time of first appearance of multiple‐resistance was 7–11 years and reached abundant levels in 10–15 years.CONCLUSIONMaintaining separate CL and PV rice systems, in rotation with other crops and herbicides, minimized the evolution of multiple herbicide‐resistant weedy rice through gene flow compared to stacking herbicide resistance traits. © 2017 Society of Chemical Industry
A multi-stage genome-wide association study of uterine fibroids in African Americans
Authors: Hellwege Jacklyn N. , Jeff Janina M. , Wise Lauren A. , Gallagher C. Scott , Wellons Melissa , Hartmann Katherine E. , Jones Sarah F. , Torstenson Eric S. , Dickinson Scott , Ruiz-Narváez Edward A. , Rohland Nadin , Allen Alexander , Reich David , Tandon Arti , Pasaniuc Bogdan , Mancuso Nicholas , Im Hae Kyung , Hinds David A. , Palmer Julie R. , Rosenberg Lynn , Denny Joshua C. , Roden Dan M. , Stewart Elizabeth A. , Morton Cynthia C. , Kenny Eimear E. , Edwards Todd L. , Velez Edwards Digna R. 
Published: August 2017

Abstract
Uterine fibroids are benign tumors of the uterus affecting up to 77% of women by menopause. They are the leading indication for hysterectomy, and account for $34 billion annually in the United States. Race/ethnicity and age are the strongest known risk factors. African American (AA) women have higher prevalence, earlier onset, and larger and more numerous fibroids than European American women. We conducted a multi-stage genome-wide association study (GWAS) of fibroid risk among AA women followed by in silico genetically predicted gene expression profiling of top hits. In Stage 1, cases and controls were confirmed by pelvic imaging, genotyped and imputed to 1000 Genomes. Stage 2 used self-reported fibroid and GWAS data from 23andMe, Inc. and the Black Women’s Health Study. Associations with fibroid risk were modeled using logistic regression adjusted for principal components, followed by meta-analysis of results. We observed a significant association among 3399 AA cases and 4764 AA controls at rs739187 (risk-allele frequency = 0.27) in CYTH4 (OR (95% confidence interval) = 1.23 (1.16–1.30), p value = 7.82 × 10−9). Evaluation of the genetic association results with MetaXcan identified lower predicted gene expression of CYTH4 in thyroid tissue as significantly associated with fibroid risk (p value = 5.86 × 10−8). In this first multi-stage GWAS for fibroids among AA women, we identified a novel risk locus for fibroids within CYTH4 that impacts gene expression in thyroid and has potential biological relevance for fibroids.
Predictability and inconsistencies in the cognitive outcome of early treated PKU patients
Authors: Manti Filippo , Nardecchia Francesca , Paci Sabrina , Chiarotti Flavia , Carducci Claudia , Carducci Carla , Dalmazzone Silvia , Cefalo Graziella , Salvatici Elisabetta , Banderali Giuseppe , Leuzzi Vincenzo 
Published: August 2017

AbstractLong‐term cognitive outcome and treatment of adult early treated (ET)PKU patients is a main issue in PKU research. We questioned whether the intellectual development of ETPKU patients is stable and to what extent its variation may be predicted by the quality of metabolic control. The aims of the present longitudinal retrospective study were to assess in young adult ETPKU patients: i) the relationship between IQ and metabolic control during the first two decades of life; and ii) the intra‐ and interindividual variability in the developmental trajectory which cannot be predicted by the disease's biomarkers. We collected biochemical data from 65 ETPKU patients (diagnostic blood Phe > 360 μmol/l) who were assessed twice for IQ (Wechsler Intelligence Scale) during their lifetime (mean age: 10.2 and 19.6 years, respectively). Results show that in ETPKU patients IQ over the second decade of life remained stable in about half of the patients (51%); while the rest experienced a gain (7 to 15 points) or loss (7 to 28 points) in IQ scores (23 and 26% respectively) whatever the quality of metabolic control was. The main factor affecting the second IQ was the value of the first IQ (p < 0.000) whose effect overruled that of the markers of metabolic control. Looking at the developmental trajectory of our ETPKU patients, the present study disclosed a remarkable interindividual variability in their cognitive outcome and also an inconsistent linkage between cognitive performances and biochemical control, thus supporting the hypothesis of an individual resilience or vulnerability to Phe in young adult ETPKU.
Nutrient Restriction Increases Circulating and Hepatic Ceramide in Dairy Cows Displaying Impaired Insulin Tolerance
Authors: Davis Amanda N. , Clegg J. L. , Perry C. A. , McFadden J. W. 
Published: August 2017

AbstractThe progression of insulin resistance in dairy cows represents a maternal adaptation to support milk production during heightened energy demand; however, excessive adipose tissue lipolysis can develop. In diabetic non‐ruminants, the mechanisms that mediate insulin resistance involve the sphingolipid ceramide. We tested the hypothesis that ceramide accumulates in dairy cows experiencing lipolysis and insulin resistance. Nine dairy cows were utilized in a replicated 3 × 3 Latin square design. Cows were ad libitum fed, nutrient‐restricted (NR), or NR with nicotinic acid (NA; 5 mg of NA/h per kg BW; delivered i.v.) for 34 h. When provided access, cows were ad libitum fed a mixed ration of grass hay and ground corn to meet requirements. Intake for NR cows was limited to vitamins and minerals. Nicotinic acid was administered to suppress lipolysis. Saline was infused in cows not provided NA. At 32 and 33 h of treatment, a liver biopsy and insulin tolerance test were performed, respectively. Samples were analyzed using colorimetry, immunoassay, and mass spectrometry. Nutrient restriction increased serum fatty acids and ceramide levels, and impaired insulin sensitivity; however, NA infusion was unable to prevent these responses. We also show that NR increases hepatic ceramide accumulation, a response that was positively associated with serum ceramide supply. Our data demonstrate that circulating and hepatic 24:0‐Cer are inversely associated with systemic insulin tolerance, an effect not observed for the 16:0 moiety. In conclusion, our results suggest that ceramide accrual represents a metabolic adaptation to nutrient restriction and impaired insulin action in dairy cows.
Widening the net: exploring social determinants of burden of informal carers
Authors: Gresswell I. , Lally L. , Adamis D. , McCarthy G. M. 
Published: August 2017

ObjectivesProviding care for a person with dementia or other chronic illness at home often places stress on the primary caregiver. In an Irish population, ~67% of carers reported experiencing extreme physical or mental tiredness. This study aimed to identify factors that influence carer burden and identify the sub-populations of carers who are most susceptible to burden.MethodsConsecutive carers referred to a local carers’ support organisation completed the following measurements: the Neuropsychiatric Inventory, Zarit Burden Interview, Social Network Index, General Health Questionnaire, Short Form Survey, Hamilton Depression Rating Scale, Brown’s Locus of Control scale and provided demographic data on themselves and their patient.ResultsThe sample consisted 53 carers, mean age: 64.5±11.7, of whom 43 (81.1%) were females. A linear regression model found significant independent (p<0.05) factors for carer burden were: increased behavioural problems of the patient, carer characteristics including female gender, younger age, high number of contacts, lower physical functioning and emotional problems, while protective factors were marriage and higher number of embedded networks.ConclusionsThe ability to predict which carers are more susceptible to burden allows service providers to more quickly and accurately identify ‘higher risk’ carers, facilitating routine check-ups by physicians and carer support services.
Post-glacial Foraminifera of the incised Yangtze paleo-valley and paleoenvironmental implications
Authors: Ke Xue , Li Baohua , Zhang Zongyan , Wei Yi , Hu Fei , Fan Dongwen , Sun Li , Xie Jianlei , Yu Junjie , Yao Huazhou 
Published: August 2017

AbstractThree gravity cores (LZK1, ZKA4, and CSJA6) from the incised Yangtze paleo-valley comprise a thick sequence of the post-glacial deposit. Nineteen genera (26 species) of the benthic foraminifers are described from these cores, with detailed down-core foraminiferal variations to investigate their paleoenvironmental implications. Three foraminiferal assemblages are recognized for the lower, middle, and upper parts of the cores respectively. The lower part is dominated byAmmonia beccariivar. andFlorilus decoruswith lower abundance and diversity. In the middle part, the foraminifers are abundant and diverse, dominated by bothAmmonia beccariivar. andElphidium advenum.Cavarotalia annectens,Pararotalia nipponica, and porcellaneous benthic foraminiferal forms are always present, sometimes abundant. The upper part is characterized by theAmmonia beccarii-Elphidium magellanicumassemblage, except for the Core ZKA4, which is barren of foraminifers in this interval. AMS14C dates and foraminiferal assemblages both confirm that the transgression-regression sequence in these cores belongs to the “Ammoniatransgression” during the Holocene. In addition to documenting the post-glacial sea-level fluctuations, the benthic foraminifers also reflect a warmer climate during the early–middle Holocene. The foraminiferal differences among the three cores can be used to interpret the influence of seawater during the post-glacial sea-level fluctuations. The area in the vicinity of Core ZKA4 was affected by marine water only during the middle Holocene, which was much shorter than the areas of the other cores.
Protein ingestion preserves proteasome activity during intense aseptic inflammation and facilitates skeletal muscle recovery in humans
Authors: Draganidis Dimitrios , Chondrogianni Niki , Chatzinikolaou Athanasios , Terzis Gerasimos , Karagounis Leonidas G. , Sovatzidis Apostolos , Avloniti Alexandra , Lefaki Maria , Protopapa Maria , Deli Chariklia K. , Papanikolaou Konstantinos , Jamurtas Athanasios Z. , Fatouros Ioannis G. 
Published: August 2017

AbstractThe ubiquitin–proteasome system (UPS) is the main cellular proteolytic system responsible for the degradation of normal and abnormal (e.g. oxidised) proteins. Under catabolic conditions characterised by chronic inflammation, the UPS is activated resulting in proteolysis, muscle wasting and impaired muscle function. Milk proteins provide sulphur-containing amino acid and have been proposed to affect muscle inflammation. However, the response of the UPS to aseptic inflammation and protein supplementation is largely unknown. The aim of this study was to investigate how milk protein supplementation affects UPS activity and skeletal muscle function under conditions of aseptic injury induced by intense, eccentric exercise. In a double-blind, cross-over, repeated measures design, eleven men received either placebo (PLA) or milk protein concentrate (PRO, 4×20 g on exercise day and 20 g/d for the following 8 days), following an acute bout of eccentric exercise (twenty sets of fifteen eccentric contractions at 30°/s) on an isokinetic dynamometer. In each trial, muscle biopsies were obtained from the vastus lateralis muscle at baseline, as well as at 2 and 8 d post exercise, whereas blood samples were collected before exercise and at 6 h, 1 d, 2 d and 8 d post exercise. Muscle strength and soreness were assessed before exercise, 6 h post exercise and then daily for 8 consecutive days. PRO preserved chymotrypsin-like activity and attenuated the decrease of strength, facilitating its recovery. PRO also prevented the increase of NF-κB phosphorylation and HSP70 expression throughout recovery. We conclude that milk PRO supplementation following exercise-induced muscle trauma preserves proteasome activity and attenuates strength decline during the pro-inflammatory phase.
Alternative Healthy Eating Index 2010, Dietary Inflammatory Index and risk of mortality: results from the Whitehall II cohort study and meta-analysis of previous Dietary Inflammatory Index and mortality studies
Authors: Shivappa Nitin , Hebert James R. , Kivimaki Mika , Akbaraly Tasnime 
Published: August 2017

AbstractWe aimed to examine the association between the Alternative Healthy Eating Index updated in 2010 (AHEI-2010), the Dietary Inflammatory Index (DIITM) and risk of mortality in the Whitehall II study. We also conducted a meta-analysis on the DII-based results from previous studies to summarise the overall evidence. Data on dietary behaviour assessed by self-administered repeated FFQ and on mortality status were available for 7627 participants from the Whitehall II cohort. Cox proportional hazards regression models were performed to assess the association between cumulative average of AHEI-2010 and DII scores and mortality risk. During 22 years of follow-up, 1001 participants died (450 from cancer, 264 from CVD). Both AHEI-2010 (mean=48·7 (sd10·0)) and DII (mean=0·37 (sd1·41)) were associated with all-cause mortality. The fully adjusted hazard ratio (HR) persd, were 0·82; 95 % CI 0·76, 0·88 for AHEI-2010 and 1·18; 95 % CI 1·08, 1·29 for DII. Significant associations were also observed with cardiovascular and cancer mortality risk. For DII, a meta-analysis (using fixed effects) from this and four previous studies showed a positive association of DII score with all-cause (HR=1·04; 95 % CI 1·03, 1·05, 28 891deaths), cardiovascular (HR=1·05; 95 % CI 1·03, 1·07, 10 424 deaths) and cancer mortality (HR=1·05; 95 % CI 1·03, 1·07,n8269).The present study confirms the validity to assess overall diet through AHEI-2010 and DII in the Whitehall II cohort and highlights the importance of considering diet indices related to inflammation when evaluating all-cause, cardiovascular and cancer mortality risk.