bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemotherapy-induced Peripheral Neuropathy Among Paediatric Oncology Patients
Authors: Purser M.J. , Johnston D.L. , McMillan H.J. 
Published: December 2014

Background:Vinca alkaloids and platinum-containing chemotherapeutic drugs have the potential to cause chemotherapy-induced peripheral neuropathy (CIPN). This study determined the frequency of CIPN among children who were treated for acute lymphoblastic leukemia (ALL), lymphoma, brain tumour or Wilms tumour.Procedure:This retrospective cohort study reviewed 252 patients treated at the Children's hospital of Eastern Ontario from 2001-2011. Patients were considered to have CIPN if they developed clinical symptoms of CIPN such as limb paraesthesia, weakness and/or ataxia during chemotherapy and their treating neurologist or oncologist deemed that their symptoms were due to a peripheral cause. Patients were excluded if their treatment regime did not include chemotherapy.Results:The overall frequency of CIPN was 18.3% (46/252). Tumour-specific CIPN rates were: 18.9% (29/154) for ALL; 9.4% (3/32) for lymphoma; 17.9% (5/28) for Wilms tumour; and 23.7% (9/38) for brain tumour patients. Nerve conduction studies were completed for 17% of patients (all tumour types) and were abnormal in all but one patient. Among surviving CIPN patients (41/46), 93% showed no clinical deficits at their last examination, which was on average 56 months from time of diagnosis to last follow-up visit.Conclusions:The frequency of CIPN was less than that previously reported in adults receiving chemotherapy. Children with CIPN have a favourable outcome with most showing clinical improvement during the maintenance phase of treatment or after chemotherapy completion.
Impact of Glucose Fluctuation on Acute Cerebral Infarction in Type 2 Diabetes
Authors: Huang Jinxin , Zhang Xingguang , Li Juan , Tang Liya , Jiao Xiumin , Lv Xiaofeng 
Published: December 2014

Objective:This study aimed to describe the frequency and temporal profile of acute cerebral infarction (ACI) using a continuous glucose monitoring system (CGMS) in patients with and without type 2 diabetes mellitus (T2DM) and explore the impact of blood glucose fluctuations on the short-term prognosis of ACI.Methods:The subjects were divided into four groups: T2DM with acute cerebral infarction (DMCI, Group A, n=56); T2DM without acute cerebral infarction (DM-NCI, Group B, n=36); Acute cerebral infarction patients without T2DM (NDM-CI, Group C, n=54); Healthy control group (NG, Group D, n=36). The National Institutes of Health Stoke Scale (NIHSS) and modified Rankin scale (mRs) were collected in Group A and C. All subjects were monitored for 72 hours using the CGMS. Indices such as fasting blood glucose (FBG) and mean amplitude of glycemic excursions (MAGE) were calculated. Glycemic excursions were compared between Group A, B, C and Group D, respectively. Multiple linear regression analysis and logistic analysis was applied.Results:MAGE is related to NIHSS, homocysteine (HCY), HOMA-IR, FBG, CRP and IMT, while NIHSS is related to CRP, HCY, HOMA-IR, IMT. The factors impacting the short-term prognosis of ACI were NIHSS, HBA1C and MAGE.Conclusion:Larger glucose fluctuations are associated with more stroke risk factors and are associated with a poorer short-term prognosis. More attention should be paid to glucose fluctuations in patients with ACI and a history of T2DM.
The Human Microbiome in Multiple Sclerosis: Pathogenic or Protective Constituents?
Authors: Power Christopher , Antony Joseph M. , Ellestad Kristofor K. , Deslauriers André , Bhat Rakesh , Noorbakhsh Farshid 
Published: December 2014

ABSTRACT:The human microbiome is comprised of commensal and pathogenic microorganisms, which exert diverse effects in close proximity to the site of intection as well as in remote tissues through immune-mediated mechanisms. Multiple infectious agents have been implicated in the pathogenesis of multiple sclerosis (MS) with variable findings depending on the agent, techniques, and disease phenotype. Herein, the contributions of individual infectious agents to MS and their effects on the immune and nervous systems are reviewed, focusing on herpes viruses, coronaviruses, retroviruses, and synchronic infections. While infectious agents are often assumed to be pathogenic, their effects might also be beneficial to the host in the long-term, depending on age and the type of immunogen/pathogen exposure, as proposed by the hygiene hypothesis. The human microbiome has potential impact on future diagnostic and therapeutic issues in MS.
What factors are associated with frequent unhealthy snack-food consumption among Australian secondary-school students?
Authors: Niven Philippa , Scully Maree , Morley Belinda , Baur Louise , Crawford David , Pratt Iain S , Wakefield Melanie 
Published: December 2014

AbstractObjectiveTo examine demographic and behavioural correlates of unhealthy snack-food consumption among Australian secondary-school students and the association between their perceptions of availability, convenience and intake with consumption.DesignCross-sectional survey of students’ eating, physical activity and sedentary behaviours using validated instruments administered via an online questionnaire.SettingAustralian secondary schools across all states/territories.SubjectsSecondary-school students aged 12–17 years participating in the 2009–10 National Secondary Students’ Diet and Activity (NaSSDA) survey (n 12 188).ResultsApproximately one in five students (21 %) reported consuming unhealthy snack foods ≥14 times/week (‘frequent snackers’). After adjusting for all covariates, older students and those with a BMI of ≥25 kg/m2 were less likely to be frequent snackers, while students who reported high fast-food and high sugar-sweetened beverage consumption and those who watched television for >2 h/d were more likely to snack frequently. Furthermore, after adjusting for all covariates and demographic factors, students who agreed that snack foods are usually available at home, convenient to buy and that they eat too many snack foods were more likely to be snacking frequently. Conversely, students who agreed that fruit is a convenient snack were less likely to be frequent snackers.ConclusionsFrequent unhealthy snack-food consumption appears to cluster with other poor health behaviours. Perceptions of availability and convenience are factors most readily amenable to change, and findings suggest interventions should focus on decreasing the availability of unhealthy snack foods in the home and promoting healthier options such as fruit as convenient snacks.
Lytic activity by temperate phages of Pseudomonas aeruginosa in long-term cystic fibrosis chronic lung infections
Authors: James Chloe E , Davies Emily V , Fothergill Joanne L , Walshaw Martin J , Beale Colin M , Brockhurst Michael A , Winstanley Craig 
Published: December 2014

Abstract
Pseudomonas aeruginosa is the most common bacterial pathogen infecting the lungs of cystic fibrosis (CF) patients. The transmissible Liverpool epidemic strain (LES) harbours multiple inducible prophages (LESϕ2; LESϕ3; LESϕ4; LESϕ5; and LESϕ6), some of which are known to confer a competitive advantage in an in vivo rat model of chronic lung infection. We used quantitative PCR (Q-PCR) to measure the density and dynamics of all five LES phages in the sputa of 10 LES-infected CF patients over a period of 2 years. In all patients, the densities of free-LES phages were positively correlated with the densities of P. aeruginosa, and total free-phage densities consistently exceeded bacterial host densities 10–100-fold. Further, we observed a negative correlation between the phage-to-bacterium ratio and bacterial density, suggesting a role for lysis by temperate phages in regulation of the bacterial population densities. In 9/10 patients, LESϕ2 and LESϕ4 were the most abundant free phages, which reflects the differential in vitro induction properties of the phages. These data indicate that temperate phages of P. aeruginosa retain lytic activity after prolonged periods of chronic infection in the CF lung, and suggest that temperate phage lysis may contribute to regulation of P. aeruginosa density in vivo.
A nairovirus isolated from African bats causes haemorrhagic gastroenteritis and severe hepatic disease in mice
Authors: Ishii Akihiro , Ueno Keisuke , Orba Yasuko , Sasaki Michihito , Moonga Ladslav , Hang’ombe Bernard M. , Mweene Aaron S. , Umemura Takashi , Ito Kimihito , Hall William W. , Sawa Hirofumi 
Published: December 2014

AbstractBats can carry important zoonotic pathogens. Here we use a combination of next-generation sequencing and classical virus isolation methods to identify novel nairoviruses from bats captured from a cave in Zambia. This nairovirus infection is highly prevalent among giant leaf-nosed bats, Hipposideros gigas (detected in samples from 16 individuals out of 38). Whole-genome analysis of three viral isolates (11SB17, 11SB19 and 11SB23) reveals a typical bunyavirus tri-segmented genome. The strains form a single phylogenetic clade that is divergent from other known nairoviruses, and are hereafter designated as Leopards Hill virus (LPHV). When i.p. injected into mice, the 11SB17 strain causes only slight body weight loss, whereas 11SB23 produces acute and lethal disease closely resembling that observed with Crimean–Congo Haemorrhagic Fever virus in humans. We believe that our LPHV mouse model will be useful for research on the pathogenesis of nairoviral haemorrhagic disease.
Identification of key binding site residues of MCT1 for AR-C155858 reveals the molecular basis of its isoform selectivity
Authors: Nancolas Bethany , Sessions Richard B. , Halestrap Andrew P. 
Published: December 2014

The proton-linked monocarboxylate transporters (MCTs) are required for lactic acid transport into and out of all mammalian cells. Thus, they play an essential role in tumour cells that are usually highly glycolytic and are promising targets for anti-cancer drugs. AR-C155858 is a potent MCT1 inhibitor (Ki ~2 nM) that also inhibits MCT2 when associated with basigin but not MCT4. Previous work [Ovens, M.J. et al. (2010) Biochem. J. 425, 523–530] revealed that AR-C155858 binding to MCT1 occurs from the intracellular side and involves transmembrane helices (TMs) 7–10. In the present paper, we generate a molecular model of MCT4 based on our previous models of MCT1 and identify residues in the intracellular substrate-binding cavity that differ significantly between MCT4 and MCT1/MCT2 and so might account for differences in inhibitor binding. We tested their involvement using site-directed mutagenesis (SDM) of MCT1 to change residues individually or in combination with their MCT4 equivalent and determined inhibitor sensitivity following expression in Xenopus oocytes. Phe360 and Ser364 were identified as important for AR-C155858 binding with the F360Y/S364G mutant exhibiting &gt;100-fold reduction in inhibitor sensitivity. To refine the binding site further, we used molecular dynamics (MD) simulations and additional SDM. This approach implicated six more residues whose involvement was confirmed by both transport studies and [3H]-AR-C155858 binding to oocyte membranes. Taken together, our data imply that Asn147, Arg306 and Ser364 are important for directing AR-C155858 to its final binding site which involves interaction of the inhibitor with Lys38, Asp302 and Phe360 (residues that also play key roles in the translocation cycle) and also Leu274 and Ser278.
Detection of brown adipose tissue and thermogenic activity in mice by hyperpolarized xenon MRI
Authors: Branca Rosa Tamara , He Ting , Zhang Le , Floyd Carlos S. , Freeman Matthew , White Christian , Burant Alex 
Published: December 2014

Significance
In recent years, there has been a growing interest in brown adipose tissue (BAT), a tissue specialized in nonshivering thermogenesis and considered to be the next therapeutic target against obesity and diabetes. However, the detection of this very sparse tissue still represents a major challenge. To our knowledge, we report the first in vivo detection of BAT and thermogenic activity by hyperpolarized xenon gas MRI. We show that during thermogenic activity a more than 15-fold enhancement in xenon uptake by BAT enables us to clearly differentiate this tissue from the surrounding tissue and to thereby overcome the major limitations of conventional imaging methods. We also use lipid-dissolved hyperpolarized xenon chemical shift to demonstrate direct in vivo MR thermometry of BAT.
Hominids adapted to metabolize ethanol long before human-directed fermentation
Authors: Carrigan Matthew A. , Uryasev Oleg , Frye Carole B. , Eckman Blair L. , Myers Candace R. , Hurley Thomas D. , Benner Steven A. 
Published: December 2014

Significance
Many modern human diseases are attributed to incompatibility between our current environment and the environment for which our genome is adapted. It is unclear whether this model applies to alcoholism. We investigated this possibility by studying alcohol dehydrogenase class IV (ADH4), the first enzyme exposed to ethanol in the digestive tract that is capable of metabolizing ethanol. We resurrected ancestral ADH4 enzymes from various points in the ∼70 million y of primate evolution and identified a single mutation occurring ∼10 million y ago that endowed our ancestors with a markedly enhanced ability to metabolize ethanol. This change occurred approximately when our ancestors adopted a terrestrial lifestyle and may have been advantageous to primates living where highly fermented fruit is more likely.
Evolution-guided optimization of biosynthetic pathways
Authors: Raman Srivatsan , Rogers Jameson K. , Taylor Noah D. , Church George M. 
Published: December 2014

Significance
Microbes can be made to produce industrially valuable chemicals in high quantities by engineering their central metabolic pathways. This process may require evaluating billions of cells, each containing a unique pathway design, to identify the rare cells with high production phenotypes. We mutated targeted locations across the genome to modify several genes identified as key players. We used sensory proteins responsive to a number of target chemicals to couple the concentration of the target chemical in each cell to individual cell fitness. This coupling of chemical production to fitness allows us to harness evolution to progressively enrich superior pathway designs. Through iterations of genetic diversification and selection, we increased the production of naringenin and glucaric acid 36- and 22-fold, respectively.
Crucial role of nonspecific interactions in amyloid nucleation
Authors: Šarić Anđela , Chebaro Yassmine C. , Knowles Tuomas P. J. , Frenkel Daan 
Published: December 2014

Significance
The assembly of normally soluble proteins into large fibrils, known as amyloid aggregation, is associated with a range of pathologies. Prefibrillar protein oligomers but not the grown fibers are believed to be the main toxic agents. It is unresolved if these oligomers are necessary for fibril assembly or just a dangerous byproduct. We show using computer simulations that, at physiological concentrations, amyloid formation must proceed through a two-step process including prefibrillar oligomers. We find that there is an optimal oligomeric size for amyloid nucleation and that classical nucleation theory cannot be applied to this process. Formation of oligomers and hence, fibrils, is controlled by the strength of nonspecific attractions, whose weakening may be crucial in preventing amyloid aggregation.
Self-assembled FUS binds active chromatin and regulates gene transcription
Authors: Yang Liuqing , Gal Jozsef , Chen Jing , Zhu Haining 
Published: December 2014

Significance
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder and mutations in fused in sarcoma (FUS) cause a subset of familial ALS. Mutant FUS forms cytoplasmic inclusions, but it is unclear whether loss of FUS function in the nucleus or toxicity gained in the cytoplasm is more critical in the ALS etiology. The physiological function of FUS is also uncharacterized. We found that a significant portion of FUS was bound to active chromatin and that ALS mutations dramatically reduced FUS chromatin binding. A high order FUS assembly is mediated by the N-terminal QGSY (glutamine-glycine-serine-tyrosine)-rich region and is required for FUS chromatin binding and the transcription activation by FUS. ALS mutations in FUS can cause its loss of function in the nucleus by disrupting this assembly and chromatin binding.
Effects of biological explanations for mental disorders on clinicians’ empathy
Authors: Lebowitz Matthew S. , Ahn Woo-kyoung 
Published: December 2014

Significance
Mental disorders are increasingly understood biologically. We tested the effects of biological explanations among mental health clinicians, specifically examining their empathy toward patients. Conventional wisdom suggests that biological explanations reduce perceived blameworthiness against those with mental disorders, which could increase empathy. Yet, conceptualizing mental disorders biologically can cast patients as physiologically different from “normal” people and as governed by genetic or neurochemical abnormalities instead of their own human agency, which can engender negative social attitudes and dehumanization. This suggests that biological explanations might actually decrease empathy. Indeed, we find that biological explanations significantly reduce clinicians’ empathy. This is alarming because clinicians’ empathy is important for the therapeutic alliance between mental health providers and patients and significantly predicts positive clinical outcomes.
In vivo selective cancer-tracking gadolinium eradicator as new-generation photodynamic therapy agent
Authors: Zhang Tao , Lan Rongfeng , Chan Chi-Fai , Law Ga-Lai , Wong Wai-Kwok , Wong Ka-Leung 
Published: December 2014

Significance
Next-generation photodynamic therapy (NG-PDT) for the treatment of tumors preponderates over conventional practices in that it is a kind of effective precision medicine with minimal invasive procedures and side effects. Herein, a newly developed NG-PDT paradigm agent of gadolinium-porphyrin complex, Gd-N, is introduced, which can successfully trace and recognize tumor tissues via simple injection into the blood vessel of the mouse models, selectively accumulate within them, and superiorly exert the therapeutic effect via cytotoxic singlet oxygen generation (∼51% quantum yield) to eradicate the solid tumor by one-half within a short period of time only upon due two-photon excitation. Its characteristic two-photon–induced near-infrared emission is also always available for direct monitoring for transportation and effectiveness in vitro and in vivo.
Practice and play in the development of German top‐level professional football players
Authors: Hornig Manuel , Aust Friedhelm , Güllich Arne 
Published: December 2014

AbstractThis study examined the developmental sporting activities of 52 German football first Bundesliga professionals (including 18 senior national team members) and 50 fourth to sixth league amateur players. They reported their volumes of organised football practice/training, including its “microstructure” (proportions of physical conditioning, skill exercises and playing forms), non‐organised leisure football play and engagement in other sports through their career, respectively. Analyses revealed that the Bundesliga professionals performed moderate amounts of organised football practice/training throughout their career. They accumulated 4264 (mean value) hours over ~16 years before debuting in 1st Bundesliga; senior National Team debut was preceded by 4532 hours (mean) over ~17 years. Within the “microstructure” of organised practice/training, the proportion of playing forms developed from ~52% (childhood) to ~45% (adolescence) and ~40% (adulthood) and physical conditioning from ~13% to ~14% and ~23%. Outside organised involvement, these players engaged in extensive non‐organised leisure football play making ~68%, ~54% and ~9% of all football involvement. Subsuming organised and non‐organised football, ~86% (childhood), ~73% (adolescence) and ~43% (adulthood) of all activity was game play (exclusive matchplay). National Team differed from amateurs in more non‐organised leisure football in childhood, more engagement in other sports in adolescence, later specialisation, and in more organised football only at age 22+ years. Relative to numerous other studies, these players performed less organised practice, particularly less physical conditioning, but greater proportions of playing activities. The findings are discussed relative to the significance of playing forms and variable involvements and are reflected against the deliberate practice and Developmental Model of Sport Participation (DMSP) frameworks.
Whole-Genome Sequencing and Epidemiological Analysis Do Not Provide Evidence for Cross-transmission of Mycobacterium abscessus in a Cohort of Pediatric Cystic Fibrosis Patients
Authors: Harris Kathryn A. , Underwood Anthony , Kenna Dervla T. D. , Brooks Anthony , Kavaliunaite Ema , Kapatai Georgia , Tewolde Rediat , Aurora Paul , Dixon Garth 
Published: December 2014

Abstract
Background.  Mycobacterium abscessus has emerged as a major pathogen in cystic fibrosis (CF) patients and has been associated with poor clinical outcomes, particularly following lung transplant. We investigated the acquisition of this bacterium in a cohort of pediatric CF patients.
Methods.  Demographic and patient location data were used to uncover epidemiological links between patients with genetically related strains of M. abscessus that had been previously typed by variable-number tandem repeat profiling. Whole-genome sequencing was applied to 27 M. abscessus isolates from the 20 patients in this cohort to provide definitive data on the genetic relatedness of strains.
Results.  Whole-genome sequencing data demonstrated that M. abscessus isolates from 16 patients were unrelated, differing by at least 34 single-nucleotide polymorphisms (SNPs) from any other isolate, suggesting that independent acquisition events have occurred. Only 2 clusters of very closely related (&lt;25 SNPs) isolates from different patients were seen. The first cluster contained 8 isolates, differing by a maximum of 17 SNPs, from a sibling pair who had intense exposure to each other both inside and outside the hospital. The second cluster contained 3 isolates, differing by a maximum of 24 SNPs, from 2 individuals with no apparent epidemiological links.
Conclusions.  We have not demonstrated cross-transmission of M. abscessus within our hospital, except between 1 sibling pair. Alternative routes of acquisition of M. abscessus infection, in particular the environment, require further investigation.