bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of next generation sequencing on the analysis of breast cancer susceptibility: a role for extremely rare genetic variation?
Authors: Hilbers FSM , Vreeswijk MPG , van Asperen CJ , Devilee P 
Published: September 2013

AbstractWomen with a family history of breast cancer have an approximately twofold elevated risk of the disease. Even though an array of genes has been associated with breast cancer risk the past two decades, variants within these genes jointly explain at most 40% of this familial risk. Many explanations for this ‘missing heritability’ have been proposed, including the existence of many very rare variants, interactions between genetic and environmental factors and structural genetic variation. In this review, we discuss how next generation sequencing will teach us more about the genetic architecture of breast cancer, with a specific focus on very rare genetic variants. While such variants potentially explain a substantial proportion of familial breast cancer, assessing the breast cancer risks conferred by them remains challenging, even if this risk is relatively high. To assess more moderate risks, epidemiological approaches will require very large patient cohorts to be genotyped for the variant, only achievable through international collaboration. How well we will be able to eventually resolve the missing heritability for breast cancer in a clinically meaningful way crucially depends on the underlying complexity of the genetic architecture.
Aleukemic cutaneous myeloid sarcoma
Authors: Aboutalebi Amir , Korman John B. , Sohani Aliyah R. , Hasserjian Robert P. , Louissaint Abner , Le Long , Kraft Stefan , Duncan Lyn M. , Nazarian Rosalynn M. 
Published: September 2013

BackgroundAleukemic cutaneous myeloid sarcoma (CMS) represents an important yet rare entity denoting the presence of a cutaneous myeloid leukemic infiltrate without concurrent peripheral blood or bone marrow disease. The clinicopathologic diagnosis remains elusive due to isolated skin findings and variable immunostaining. Cytogenetic and molecular findings have infrequently been reported.MethodsTwenty‐five patients with CMS were identified in the Massachusetts General Hospital pathology database between 2004 and 2012. Patients were excluded if concurrent blood or marrow acute myeloid leukemia (AML), myelodysplastic syndrome or lymphoproliferative disorder were diagnosed.ResultsThree patients were identified: a neonate with recurrent CMS and marrow disease that never met diagnostic criteria for AML and two patients relapsing as CMS without concurrent blood or marrow disease following chemotherapy‐induced complete remission. Histology showed atypical mononuclear cell interstitial dermal infiltrates. All cases were CD68+, lysozyme+ and CD117−; one of two were CD34+; two of three were myeloperoxidase negative. 11q23 rearrangement, t(1;14), NPM1 (nucleophosmin I), FLT3‐ITD (Fms‐like tyrosine kinase 3‐internal tandem duplication), and novel FLT3‐D835 mutations were identified.ConclusionAn isolated atypical cutaneous infiltrate may represent aleukemic CMS and should prompt a search for other extramedullary sites of involvement. Immunohistochemistry, molecular and cytogenetic studies can help differentiate aleukemic CMS from benign and malignant, monocytic and histiocytic mimickers, and may potentially indicate therapy and prognosis.
Hydroacoustic assessment of mono‐ and polymorphic Coregonus density and biomass in subarctic lakes
Authors: Malinen Tommi , Tuomaala Antti , Lehtonen Hannu , Kahilainen Kimmo K. 
Published: September 2013

AbstractDensity and biomass estimates of pelagic fish are essential to understand food web interactions and ecosystem functioning. We conducted surveys of six subarctic lakes for assessing both mono‐ and polymorphic whitefish Coregonus lavaretus (L.) populations. Monomorphic whitefish lakes were inhabited by a habitat and diet generalist, large sparsely rakered (LSR) morph, whereas polymorphic whitefish lakes had a littoral benthivorous LSR morph, a pelagic planktivorous densely rakered (DR) morph and in two cases a benthivorous small sparsely rakered (SSR) morph inhabiting the profundal zone. In addition, an introduced specialist zooplanktivore, vendace Coregonus albula (L.), inhabited one of the monomorphic lakes. Hydroacoustics was found to be an appropriate method for estimating coregonid densities and biomasses in large and deep polymorphic lakes occupied by the planktivorous DR morph or vendace, but only during dark nights in autumn. The suitability of hydroacoustic assessment for benthivorous LSR and SSR morphs was low, especially in polymorphic whitefish lakes due to their preference for near‐bottom habitat or shallow areas not sampled with hydroacoustics. The pelagic density of DR morph varied from 330 to 1780 fish·ha−1 and biomass from 1.4 to 13.3 kg·ha−1 in polymorphic whitefish lakes, whereas corresponding estimates for LSR morph were 10–320 fish·ha−1 and 0.5–8.4 kg·ha−1 in monomorphic whitefish lakes. In general, polymorphism tended to increase the density and biomass of whitefish in the pelagic area compared with monomorphic systems.
The importance of spatial scales to analysis of fish diversity in Amazonian floodplain lakes and implications for conservation
Authors: Freitas Carlos E.C. , Siqueira‐Souza Flávia K. , Florentino Alexandro C. , Hurd Lawrence E. 
Published: September 2013

AbstractThe Amazon River Basin has the highest fish species diversity of any region in the world, but is under threat from anthropogenic perturbations including overharvesting, alien species and drought. We asked whether species diversity in this region is more a function of within‐lake species richness (i.e., α diversity) or differences among lakes (β diversity). Although many studies have reported on species richness and diversity in single habitats, the importance of measuring diversity at different spatial scales is not yet well established. We collected fish in 10 floodplain lakes along the Solimões River (Brazil), divided evenly between two lake types: those on islands in the river channel (island lakes) and those on the margins of the river (coastal lakes) during 2006. We partitioned fish diversity into three spatial scales: α = within each lake; β1 = among lakes of the same type (coastal or island) and β2 = between the two types of lakes, and compared their relative contributions to regional (γ) diversity. β1 + β2 contributed as much or more to γ diversity than did α. Although many of the 116 fish species were shared between lake types (S = 72), 32 species were found exclusively in coastal lakes and 12 species were found exclusively in island lakes. Coastal lakes, which were deeper and cooler than island lakes, consistently had higher fish species richness than island lakes. We suggest that it will be necessary to set areas large enough to contain multiple lakes of both types to preserve regional fish diversity.
Is there a one‐way street from essential tremor to Parkinson's disease? Possible biological ramifications
Authors: Louis E. D. , Ottman R. 
Published: September 2013

There is considerable evidence for an association between essential tremor (ET) and Parkinson's disease (PD), although the topic remains somewhat controversial. An important issue, not previously addressed, is what seems to be the unidirectional nature of the relationship (ET→ET + PD and not PD→PD + ET). The aims of this review are (i) to discuss the evidence for and against a unidirectional relationship and (ii) to discuss the implications of such a unidirectional relationship, if it exists, for disease mechanisms. Evidence ‘for’ a unidirectional relationship includes (i) abundant clinical anecdotal observation and (ii) clinical and epidemiological studies. Evidence ‘against’ is theoretical rather than empirical. Overall, the evidence ‘for’ is stronger, although additional studies are needed in order to be certain; for the time being, it might be best to leave this as an open question. The biological ramifications/extensions of such a unidirectional relationship include (i) that the association is causal (i.e. some aspect of ET pathophysiology predisposes an individual to develop PD) and (ii) that some ET cases may have a circumscribed form of Lewy body disease, and the secondary development of PD may represent a spread of those Lewy bodies in the brainstem. The presence and nature of the links between ET and PD are controversial. Further primary data (epidemiological and pathological) are needed to improve understanding of the relationship and its implications for the pathogenesis of both disorders.
Deciphering the pro‐fibrotic phenotype of fibroblasts in systemic sclerosis
Authors: Maier Christiane , Distler Jörg H. W. , Beyer Christian 
Published: September 2013

AbstractLeRoy's seminal work on the phenotypic features of scleroderma fibroblasts has been directing fibrosis research in the field of systemic sclerosis (SSc, scleroderma) for the past 30 years. His principal experiment, to culture skin fibroblasts from patients with SSc and study their pro‐fibrotic phenotype in comparison with skin fibroblasts from healthy individuals, has been used by most basic and translational fibrosis studies in SSc. LeRoy's findings have revolutionized our understanding of the disease pathogenesis and guided the development of novel antifibrotic therapies towards fibroblast‐specific approaches.
A S52P mutation in the ‘α‐crystallin domain’ of Mycobacterium leprae HSP18 reduces its oligomeric size and chaperone function
Authors: Nandi Sandip K. , Rehna Elengikal A. A. , Panda Alok K. , Shiburaj Sugathan , Dharmalingam Kuppamuthu , Biswas Ashis 
Published: September 2013

Mycobacterium leprae HSP18 is a small heat shock protein (sHSP). It is a major immunodominant antigen of M. leprae pathogen. Previously, we have reported the existence of two M. leprae HSP18 variants in various leprotic patients. One of the variants has serine at position 52, whereas the other one has proline at the same position. We have also reported that HSP18 having proline at position 52 (HSP18P52) is a nonameric protein and exhibits chaperone function. However, the structural and functional characterization of wild‐type HSP18 having serine at position 52 (HSP18S52) is yet to be explored. Furthermore, the implications of the S52P mutation on the structure and chaperone function of HSP18 are not well understood. Therefore, we cloned and purified these two HSP18 variants. We found that HSP18S52 is also a molecular chaperone and an oligomeric protein. Intrinsic tryptophan fluorescence and far‐UV CD measurements revealed that the S52P mutation altered the tertiary and secondary structure of HSP18. This point mutation also reduced the oligomeric assembly and decreased the surface hydrophobicity of HSP18, as revealed by HPLC and 4,4′‐dianilino‐1,1′‐binaphthyl‐5,5′‐disulfonic acid binding studies, respectively. Mutant protein was less stable against thermal and chemical denaturation and was more susceptible towards tryptic cleavage than wild‐type HSP18. HSP18P52 had lower chaperone function and was less effective in protecting thermal killing of Escherichia coli than HSP18S52. Taken together, our data suggest that serine 52 is important for the larger oligomerization and chaperone function of HSP18. Because both variants differ in stability and function, they may have different roles in the survival of M. leprae in infected hosts.Structured digital abstract

HSP18 and HSP18 bind by molecular sieving (View interaction)
Release of Chromium from Soils with Persulfate Chemical Oxidation
Authors: Kaur Kawalpreet , Crimi Michelle 
Published: September 2013

AbstractAn important part of the evaluation of the effectiveness of persulfate in situ chemical oxidation (ISCO) for treating organic contaminants is to identify and understand its potential impact on metal co‐contaminants in the subsurface. Chromium is a redox‐sensitive and toxic metal the release of which poses considerable risk to human health. The objective of this study was to investigate the impact of persulfate chemical oxidation on the release of chromium from three soils varying in physical‐chemical properties. Soils were treated with unactivated and activated persulfate [activated with Fe(II), Fe(II)‐EDTA, and alkaline pH] at two different concentrations (i.e., 41 mM and 2.1 mM persulfate) for 48 h and 6 months and were analyzed for release of chromium. Results show that release of chromium with persulfate chemical oxidation depends on the soil type and the activation method. Sandy soil with low oxidant demand released more chromium compared to soils with high oxidant demand. More chromium was released with alkaline pH activation. Alkaline pH and high Eh conditions favor oxidation of Cr(III) to Cr(VI), which is the main mechanism of release of chromium with persulfate chemical oxidation. Unactivated and Fe(II)‐activated persulfate decreased pH and at low pH in absence of EDTA chromium release is not a concern. These results indicate that chromium release can be anticipated based on the given site and treatment conditions, and ISCO system can be designed to minimize potential chromium release when treating soils and groundwater contaminated with both organic and metal contaminants.
Preterm delivery risk in women initiating antiretroviral therapy to prevent HIV mother‐to‐child transmission
Authors: Short C‐ES , Douglas M , Smith JH , Taylor GP 
Published: September 2013

ObjectivesThe aim of the study was to describe the relationship between preterm delivery (PTD; < 37 weeks of gestation) and antiretroviral therapy in a single‐centre cohort of pregnant women with HIV infection.MethodsA retrospective analysis of data for 331 women who received care in a dedicated HIV antenatal clinic between 1996 and 2010 was carried out. Data on first CD4 cell count and viral load (HIV‐1 RNA copies/mL) recorded in pregnancy, class and timing of antiretroviral therapy, gestational age at delivery, and risk factors for and causes of PTD were available from a clinical database.ResultsOverall, 13.0% of deliveries were preterm, of which 53% were severe preterm (< 34 weeks of gestation). The lowest rate of PTD was observed in women treated with zidovudine monotherapy (6.2%). Higher rates of PTD were observed in women starting combination antiretroviral therapy (cART) in pregnancy compared with women conceiving while on cART [odds ratio (OR) 2.52; 95% confidence interval (CI) 1.22–5.20; P = 0.011]. Of the women who were eligible for zidovudine monotherapy on the basis of CD4 counts and HIV viral load but who were treated with short‐term cART to prevent HIV mother‐to‐child transmission, 28.6% delivered preterm. Women on short‐term cART remained at the highest risk of PTD compared with zidovudine monotherapy in multivariate analysis (OR 5.00; 95% CI 1.49–16.79; P = 0.015).ConclusionsThe causes of PTD are multiple and poorly understood. The timing of initiation and type of antiretroviral therapy administered during pregnancy appear to contribute to PTD risk. Understanding this association should improve the safety of antiretroviral therapy in pregnancy without increasing the risk of transmission.
Program for the Epidemiological Evaluation of Stroke in Tandil, Argentina (PREVISTA) Study: Rationale and Design
Authors: Sposato Luciano A. , Coppola Mariano L. , Altamirano Juan , Guerrero Brenda Borrego , Casanova Jorge , De Martino Maximiliano , Díaz Alejandro , Feigin Valery L. , Funaro Fernando , Gradillone María E. , Lewin María L. , Lopes Renato D. , López Daniel H. , Louge Mariel , Maccarone Patricia , Martens Cecilia , Miguel Marcelo , Rabinstein Alejandro , Morasso Hernán , Riccio Patricia M. , Saposnik Gustavo , Silva Damián , Suasnabar Ramón , Truelsen Thomas , Uzcudun Araceli , Viviani Carlos A. , Bahit M. Cecilia 
Published: September 2013

The availability of population-based epidemiological data on the incident risk of stroke is very scarce in Argentina and other Latin American countries. In response to the priorities established by the World Health Organization and the United Nations, PREVISTA was envisaged as a population-based program to determine the risk of first-ever and recurrent stroke and transient ischemic attack incidence and mortality in Tandil, Buenos Aires, Argentina. The study will be conducted according to Standardized Tools for Stroke Surveillance (STEPS Stroke) methodology and will enroll all new (incident) and recurrent consecutive cases of stroke and transient ischemic attack in the City of Tandil between May 1st, 2013 and April 30, 2015. The study will include patients with ischemic stroke, non-traumatic primary intracerebral hemorrhage, subarachnoid hemorrhage, and transient ischemic attack. To ensure the inclusion of every cerebrovascular event during an observation period of two years, we will instrument an ‘intensive screening program’, consisting of a comprehensive daily tracking of every potential event of stroke or transient ischemic attack using multiple overlapping sources. Mortality would be determined during follow-up for every enrolled patient. Also, fatal community events would be screened daily through revision of death certificates at funeral homes and local offices of vital statistics. All causes of death will be adjudicated by an ad-hoc committee. The close population of Tandil is representative of a large proportion of Latin-American countries with low- and middle-income economies. The findings and conclusions of PREVISTA may provide data that could support future health policy decision-making in the region.
FAST INdiCATE Trial Protocol. Clinical Efficacy of Functional Strength Training for Upper Limb Motor Recovery Early after Stroke: Neural Correlates and Prognostic Indicators
Authors: Pomeroy Valerie M. , Ward Nick S. , Johansen-Berg Heidi , van Vliet Paulette , Burridge Jane , Hunter Susan M. , Lemon Roger N. , Rothwell John , Weir Christopher J. , Wing Alan , Walker Andrew A. , Kennedy Niamh , Barton Garry , Greenwood Richard J. , McConnachie Alex 
Published: September 2013

Rationale Functional strength training in addition to conventional physical therapy could enhance upper limb recovery early after stroke more than movement performance therapy plus conventional physical therapy. Aims To determine (a) the relative clinical efficacy of conventional physical therapy combined with functional strength training and conventional physical therapy combined with movement performance therapy for upper limb recovery; (b) the neural correlates of response to conventional physical therapy combined with functional strength training and conventional physical therapy combined with movement performance therapy; (c) whether any one or combination of baseline measures predict motor improvement in response to conventional physical therapy combined with functional strength training or conventional physical therapy combined with movement performance therapy. Design Randomized, controlled, observer-blind trial. Study The sample will consist of 288 participants with upper limb paresis resulting from a stroke that occurred within the previous 60 days. All will be allocated to conventional physical therapy combined with functional strength training or conventional physical therapy combined with movement performance therapy. Functional strength training and movement performance therapy will be undertaken for up to 1·5 h/day, five-days/week for six-weeks. Outcomes and Analysis Measurements will be undertaken before randomization, six-weeks thereafter, and six-months after stroke. Primary efficacy outcome will be the Action Research Arm Test. Explanatory measurements will include voxel-wise estimates of brain activity during hand movement, brain white matter integrity (fractional anisotropy), and brain–muscle connectivity (e.g. latency of motor evoked potentials). The primary clinical efficacy analysis will compare treatment groups using a multilevel normal linear model adjusting for stratification variables and for which therapist administered the treatment. Effect of conventional physical therapy combined with functional strength training versus conventional physical therapy combined with movement performance therapy will be summarized using the adjusted mean difference and 95% confidence interval. To identify the neural correlates of improvement in both groups, we will investigate associations between change from baseline in clinical outcomes and each explanatory measure. To identify baseline measurements that independently predict motor improvement, we will develop a multiple regression model.
Protocol for Seizure Prophylaxis following Intracerebral Hemorrhage Study (SPICH): A Randomized, Double-Blind, Placebo-Controlled Trial of Short-Term Sodium Valproate Prophylaxis in Patients with Acute Spontaneous Supratentorial Intracerebral Hemorrhage
Authors: Hu X. , Fang Y. , Li H. , Liu W. , Lin S. , Fu M. , Li X. , Cao X. , Zhang H. , You C. , Liu M. 
Published: September 2013

Rationale Seizures after intracerebral hemorrhage are a common complication and may adversely affect neurological outcome. However, studies are inadequate on the utility of prophylactic anticonvulsant therapy in patients with hemorrhagic stroke, and the results remains controversial. Aims This study aims to determine if short-duration sodium valproate prevents seizure onset or improves the survival and neurological outcome in adults after acute spontaneous supratentorial intracerebral hemorrhage. Design In this randomized, double blinded, placebo-controlled trial, 258 patients meeting the inclusion criteria will be enrolled in the Department of Neurosurgery, West China Hospital. In addition to standard care, patients will be randomly assigned to receive seven-day prophylaxis of sodium valproate 500 mg daily (alternatively 400 mg daily by intravenous infusion in 250 ml 0·9% normal saline) or matching placebo. Patients will be followed up at seven-days, 3, 6, and 12 months. Study outcomes The primary outcomes are early (≤7 days) and late onset seizures (>7 days). Secondary outcomes include midline shift, enlargement of hematoma, death (all cause), adverse effects, and functional outcome assessed by Glasgow Outcome Scale and modified Rankin Scale. Discussion Given the lack of evidence for seizure prophylaxis in patients with acute supratentorial intracerebral hemorrhage, randomized controlled trials are desperately needed. The results from our study are believed to directly influence future prophylactic anticonvulsant therapy of intracerebral hemorrhage.
Mobilization and Toxicity Potential of Aluminum from Alum Floc Deposits in Kensico Reservoir, New York
Authors: Driscoll Charles T. , Lee Ashley , Montesdeoca Mario , Matthews David A. , Effler Steven W. 
Published: September 2013

AbstractThere is detailed literature on the mobilization of aluminum (Al) from soil to surface waters as a result of elevated acidic deposition to base‐poor forest watersheds. There is considerably less information on the mobilization and effects of Al from the application of alum that is used in some water supplies to control turbidity during high‐flow events. We report on the results of field measurements, laboratory sediment release experiments, and chemical equilibrium calculations conducted to evaluate the potential for the mobilization of Al from alum floc deposits in sediments of Kensico Reservoir, New York. Under ambient water quality conditions, mobilization of sediment Al is not a noteworthy concern at Kensico Reservoir. However, under experimental conditions of low pH, low acid neutralizing capacity (ANC), and low temperature, the inorganic fraction of monomeric Al can be mobilized from Kensico sediments to concentrations that would likely impair the health of aquatic organisms (>2 μmol/l). Elevated concentrations of monomeric Al were observed only when ANC decreased below 50 μeq/l, which is outside the range of values observed in Kensico during the 1997‐2007 interval (120‐460 μeq/l). Concentrations of complexing ligands are relatively low in Kensico waters (i.e., fluoride, naturally occurring organic solutes) and do not appear to substantially contribute to potential Al mobilization. For other water supplies with low ANC, the potential for sediment release of Al may exist.