bluuebunny/crossref_metadata_2025_split huggingface dataset:
Solving a 50 year mystery of a missing OPA1 mutation: more insights from the first family diagnosed with autosomal dominant optic atrophy
Authors: Fuhrmann Nico , Schimpf Simone , Kamenisch York , Leo-Kottler Beate , Alexander Christiane , Auburger Georg , Zrenner Eberhart , Wissinger Bernd , Alavi Marcel V 
Published: June 2010

Abstract

Background
Up to the 1950s, there was an ongoing debate about the diversity of hereditary optic neuropathies, in particular as to whether all inherited optic atrophies can be ascribed to Leber's hereditary optic neuropathy (LHON) or represent different disease entities. In 1954 W. Jaeger published a detailed clinical and genealogical investigation of a large family with explicit autosomal dominant segregation of optic atrophy thus proving the existence of a discrete disease different from LHON, which is nowadays known as autosomal dominant optic atrophy (ADOA). Since the year 2000 ADOA is associated with genomic mutations in the OPA1 gene, which codes for a protein that is imported into mitochondria where it is required for mitochondrial fusion. Interestingly enough, the underlying mutation in this family has not been identified since then.

Results
We have reinvestigated this family with the aim to identify the mutation and to further clarify the underlying pathomechanism. Patients showed a classical non-syndromic ADOA. The long term deterioration in vision in the two teenagers examined 50 years later is of particular note 5/20 to 6/120. Multiplex ligation probe amplification revealed a duplication of the OPA1 exons 7-9 which was confirmed by long distance PCR and cDNA analysis, resulting in an in-frame duplication of 102 amino acids. Segregation was verified in 53 available members of the updated pedigree and a penetrance of 88% was calculated. Fibroblast cultures from skin biopsies were established to assess the mitochondrial network integrity and to qualitatively and quantitatively study the consequences of the mutation on transcript and protein level. Fibroblast cultures demonstrated a fragmented mitochondrial network. Processing of the OPA1 protein was altered. There was no correlation of the OPA1 transcript levels and the OPA1 protein levels in the fibroblasts. Intriguingly an overall decrease of mitochondrial proteins was observed in patients' fibroblasts, while the OPA1 transcript levels were elevated.

Conclusions
The thorough study of this family provides a detailed clinical picture accompanied by a molecular investigation of patients' fibroblasts. Our data show a classic OPA1-associated non-syndromic ADOA segregating in this family. Cell biological findings suggest that OPA1 is regulated by post-translational mechanisms and we would like to hypothesize that loss of OPA1 function might lead to impaired mitochondrial quality control. With the clinical, genetic and cell biological characterisation of a family described already more than 50 years ago, we span more than half a century of research in optic neuropathies.
Holmium-166 radioembolization for the treatment of patients with liver metastases: design of the phase I HEPAR trial
Authors: Smits Maarten LJ , Nijsen Johannes FW , van den Bosch Maurice AAJ , Lam Marnix GEH , Vente Maarten AD , Huijbregts Julia E , van het Schip Alfred D , Elschot Mattijs , Bult Wouter , de Jong Hugo WAM , Meulenhoff Pieter CW , Zonnenberg Bernard A 
Published: June 2010

Abstract

Background
Intra-arterial radioembolization with yttrium-90 microspheres ( 90Y-RE) is an increasingly used therapy for patients with unresectable liver malignancies. Over the last decade, radioactive holmium-166 poly(L-lactic acid) microspheres ( 166Ho-PLLA-MS) have been developed as a possible alternative to 90Y-RE. Next to high-energy beta-radiation, 166Ho also emits gamma-radiation, which allows for imaging by gamma scintigraphy. In addition, Ho is a highly paramagnetic element and can therefore be visualized by MRI. These imaging modalities are useful for assessment of the biodistribution, and allow dosimetry through quantitative analysis of the scintigraphic and MR images. Previous studies have demonstrated the safety of 166Ho-PLLA-MS radioembolization ( 166Ho-RE) in animals. The aim of this phase I trial is to assess the safety and toxicity profile of 166Ho-RE in patients with liver metastases.

Methods
The HEPAR study (Holmium Embolization Particles for Arterial Radiotherapy) is a non-randomized, open label, safety study. We aim to include 15 to 24 patients with liver metastases of any origin, who have chemotherapy-refractory disease and who are not amenable to surgical resection. Prior to treatment, in addition to the standard technetium-99m labelled macroaggregated albumin ( 99mTc-MAA) dose, a low radioactive safety dose of 60-mg 166Ho-PLLA-MS will be administered. Patients are treated in 4 cohorts of 3-6 patients, according to a standard dose escalation protocol (20 Gy, 40 Gy, 60 Gy, and 80 Gy, respectively). The primary objective will be to establish the maximum tolerated radiation dose of 166Ho-PLLA-MS. Secondary objectives are to assess tumour response, biodistribution, performance status, quality of life, and to compare the 166Ho-PLLA-MS safety dose and the 99mTc-MAA dose distributions with respect to the ability to accurately predict microsphere distribution.

Discussion
This will be the first clinical study on 166Ho-RE. Based on preclinical studies, it is expected that 166Ho-RE has a safety and toxicity profile comparable to that of 90Y-RE. The biochemical and radionuclide characteristics of 166Ho-PLLA-MS that enable accurate dosimetry calculations and biodistribution assessment may however improve the overall safety of the procedure.

Trial registration
ClinicalTrials.gov NCT01031784
How the relationships between general practitioners and intensivists can be improved: the general practitioners' point of view
Authors: Etesse Bérengère , Jaber Samir , Mura Thibault , Leone Marc , Constantin Jean-Michel , Michelet Pierre , Zoric Lana , Capdevila Xavier , Malavielle François , Allaouchiche Bernard , Orban Jean-Christophe , Fabbro-Peray Pascale , Lefrant Jean-Yves ,   the AzuRéa Group
Published: June 2010

Abstract
Introduction
The present study assessed the opinion of general practitioners (GPs) concerning their relationships with intensivists.

Methods
An anonymous questionnaire was mailed to 7,239 GPs. GPs were asked about their professional activities, postgraduate intensive care unit (ICU) training, the rate of patient admittance to ICUs, and their relationships with intensivists. Relationship assessment was performed by using a graduated visual analogue scale (VAS) ranging from 0 (dissatisfaction) to 100 (satisfaction). A multivariate analysis with stepwise logistic regression was performed to isolate factors explaining dissatisfaction (VAS score, < 25th percentile).

Results
Twenty-two percent of the GPs (1,561) responded. The median satisfaction score was 57 of 100 (interquartile (IQ), 35 to 77]. Five independent factors of dissatisfaction were identified: no information provided to GPs at patient admission (odds ratio (OR) = 2.55 (1.71 to 3.80)); poor quality of family reception in the ICU (OR = 2.06 (1.40 to 3.02)); the ICU's family contact person's identity or function or both is unclear (OR = 1.48 (1.03 to 2.12)), lack of family information (OR = 2.02 (2.48 to 2.75)), and lack of discharge report (OR = 3.39 (1.70 to 6.76)). Three independent factors prevent dissatisfaction: age of GPs ≤45 years (OR = 0.69 (0.51 to 0.94)); the GP is called at patient ICU admission (OR = 0.44 (0.31 to 0.63)); and GP involvement in treatment decisions (OR = 0.17 (0.07 to 0.40)).

Conclusions
Considerable improvement in GP/intensivist relationships can be achieved through increased communication measures.
Kinetics of plasmatic cytokines and cystatin C during and after hemodialysis in septic shock-related acute renal failure
Authors: Mayeur Nicolas , Rostaing Lionel , Nogier Marie B , Jaafar Acil , Cointault Olivier , Kamar Nassim , Conil Jean M , Fourcade Olivier , Lavayssiere Laurence 
Published: June 2010

Abstract
Introduction
Cystatin C could be a relevant residual glomerular filtration rate marker during hemodialysis (HD), and a high cytokine plasma (p) rate is associated with an increase in mortality during sepsis. To the best of our knowledge, cytokines and cystatin C kinetics during and after HD during sepsis have never been studied. In this study, we described p cytokines and cystatin C variations during and after hemodialysis in septic-shock patients with acute kidney injury (AKI).

Methods
Ten patients, from two tertiary ICUs, with septic shock-related AKI, according to RIFLE class F, were studied. In this prospective observational study, blood samples were collected at the start, after 1 hour, 2 hours, and at the end of HD with a polymethymethacrylate (PMMA) hemodialyzer (D0, D1, D2, and endD), and 30, 60, 90, 120, and 180 min after HD (postD0.5, postD1, postD1.5, postD2, and postD3). We measured p interleukins (IL)-6, IL-8, IL-10, cystatin C, and albumin. Results are expressed as variations from D0 (mean ± SD).

Results
During HD, p[IL-6] did not vary significantly, whereas p[IL-8] and p[IL-10] reductions by D1 were 31.8 ± 21.2% and 36.3 ± 26%, respectively (P < 0.05 as compared with D0). At postD3, p[IL-8] and p[IL-10] returned to their initial values. p[Cystatin C] was significantly reduced from D1 to postD1, with a maximal reduction of 30 ± 6.7% on D2 (P < 0.05). Norepinephrine infusion rate decreased from D0 to postD3 (0.65 ± 0.39 to 0.49 ± 0.37 μg/kg/min; P < 0.05).

Conclusions
HD allows a transient and selective decrease in p cytokines, which are known as being correlated with mortality during septic shock. Because of a significant decrease in p cystatin C during HD, this should not be considered as an accurate marker for residual glomerular filtration rate during septic acute renal failure when receiving HD with a PMMA hemodialyzer.
High-throughput sequencing identifies STAT3 as the DNA-associated factor for p53-NF-κB-complex-dependent gene expression in human heart failure
Authors: Choy Mun-Kit , Movassagh Mehregan , Siggens Lee , Vujic Ana , Goddard Martin , Sánchez Ana , Perkins Neil , Figg Nichola , Bennett Martin , Carroll Jason , Foo Roger 
Published: June 2010

Abstract
Background
Genome-wide maps of DNA regulatory elements and their interaction with transcription factors may form a framework for understanding regulatory circuits and gene expression control in human disease, but how these networks, comprising transcription factors and DNA-binding proteins, form complexes, interact with DNA and modulate gene expression remains largely unknown.

Methods
Using microRNA-21 (mir-21), which is an example of genes that are regulated in heart failure, we performed chromatin immunoprecipitation (ChIP) assays to determine the occupancy of transcription factors at this genetic locus. Tissue ChIP was further performed using human hearts and genome-wide occupancies of these transcription factors were analyzed by high-throughput sequencing.

Results
We show that the transcription factor p53 piggy-backs onto NF-κB/RELA and utilizes the κB-motif at a cis-regulatory region to control mir-21 expression. p53 behaves as a co-factor in this complex because despite a mutation in its DNA binding domain, mutant p53 was still capable of binding RELA and the cis-element, and inducing mir-21 expression. In dilated human hearts where mir-21 upregulation was previously demonstrated, the p53-RELA complex was also associated with this cis-element. Using high-throughput sequencing, we analyzed genome-wide binding sites for the p53-RELA complex in diseased and control human hearts and found a significant overrepresentation of the STAT3 motif. We further determined that STAT3 was necessary for the p53-RELA complex to associate with this cis-element and for mir-21 expression.

Conclusions
Our results uncover a mechanism by which transcription factors cooperate in a multi-molecular complex at a cis-regulatory element to control gene expression.
Synthesis and Crystal Structures of 1,4,8,11-Tetraalkyl-6,13-diphenylpentacenes
Authors: Kitamura Chitoshi , Naito Takao , Yoneda Akio , Kawase Takeshi , Komatsu Toshiki 
Published: June 2010

Abstract
Two 1,4,8,11-tetraalkyl-6,13-diphenylpentacenes were prepared. X-ray analysis revealed that the methyl derivative had a herringbone arrangement with π-overlap, while the propyl derivative had a slipped-parallel structure without π-overlap. The solid-state order reflected UV–vis absorption spectra in the solid state.
Polymerase Chain Reaction Detection of HPV in Squamous Carcinoma of the Oropharynx
Authors: Agoston Elin S. , Robinson Stephen J. , Mehra Karishma K. , Birch Chandler , Semmel Dana , Mirkovic Jelena , Haddad Robert I. , Posner Marshall R. , Kindelberger David , Krane Jeffrey F. , Brodsky Joshua , Crum Christopher P. 
Published: June 2010

Abstract
Human papillomavirus (HPV) testing is routinely performed on oropharyngeal carcinomas. We compared the Access Genetics (Minneapolis, MN) polymerase chain reaction (PCR) assay (AGPCR), DNA-DNA in situ hybridization (ISH; Ventana, Tucson, AZ), and HPV-16 E7 PCR amplification in consecutively accessioned oropharyngeal cancers. We tested 126 cases by both PCR methods; 102 were positive by either for a maximum positive rate (MPR) of 81.0%. Relative to the MPR, the sensitivities of AGPCR and E7 PCR were 90.2% and 72.5%, respectively. Of 17 AGPCR+ cases tested by ISH, 14/14 unequivocally positive/negative were concordant. All cases (97/97) positive by either PCR assay were positive for p16. There was no relationship between level of histologic differentiation and HPV status. ISH and AGPCR have comparable performance for the detection of HPV in oropharyngeal carcinomas. PCR is a suitable and economical assay that is comparable to ISH in sensitivity and may provide logistical advantages relative to ISH for assessing HPV status in oropharyngeal malignancies. However, it is imperative that appropriate sensitivity controls be in place for such assays.
To Count and How to Count, That Is the Question
Authors: Parkash Vinita , Bifulco Carlo , Feinn Richard , Concato John , Jain Dhanpat 
Published: June 2010

Abstract
Optimal cancer staging requires retrieval of a minimal number of nodes. However, variability among pathologists in counting on a slide has not been studied. To study the differences in node counting among pathologists, 10 pathologists counted nodes on 15 slides on 2 occasions. They also opined on whether selected “structures” represented countable nodes. There was no slide on which all pathologists agreed on all occasions. The greatest variability was on slides on which the number of nodes exceeded 8. There was disagreement on the size of the smallest countable node, on how to count 2 closely related structures, and when the gross disagreed with the microscopic finding. With a mean count of 5.7 nodes per slide, the 95% confidence interval was ± 2.6, which could be clinically significant when the count approaches the set minimum. Uniform criteria are necessary to allow for meaningful comparisons between studies on minimal nodal counts for cancer lymphadenectomies.
Seasonality of caulerpenyne content in native Caulerpa prolifera and invasive C. taxifolia and C. racemosa var. cylindracea in the western Mediterranean Sea
Authors: Box Antonio , Sureda Antoni , Tauler Pere , Terrados Jorge , Marbà Nuria , Pons Antoni , Deudero Salud 
Published: June 2010

Abstract
Fronds had higher mean caulerpenyne concentration than stolons in Caulerpa prolifera, C. taxifolia and C. racemosa. C. prolifera had higher mean caulerpenyne content [7.29±0.64% caulerpenyne/frond dry weight (DW)] than C. taxifolia (5.47±0.32% caulerpenyne/frond DW) and C. racemosa (0.43±0.07% caulerpenyne/frond DW). C. prolifera had reduced content from May to October in fronds, with no clear seasonal pattern in stolons. C. taxifolia reached a maximum caulerpenyne value in fronds in May, with a slight decrease until the onset of winter; there was no clear seasonal trend in stolons. Caulerpenyne content remained relatively constant through the year in fronds of C. racemosa; stolons showed a clear seasonal pattern of increasing caulerpenyne content in spring, reaching maximum values at the end of summer, and decreasing during winter. C. prolifera caulerpenyne contents were positively correlated with densities of the Caulerpa-feeding gastropod Ascobulla fragilis (ρ=0.84, p<0.05). The main finding of the present work is that C. prolifera has higher caulerpenyne concentrations than invasive Caulerpa species under similar climate conditions.
Risk Factors for Invasive Pneumococcal Disease in Children in the Era of Conjugate Vaccine Use
Authors: Pilishvili Tamar , Zell Elizabeth R. , Farley Monica M. , Schaffner William , Lynfield Ruth , Nyquist Ann-Christine , Vazquez Marietta , Bennett Nancy M. , Reingold Arthur , Thomas Ann , Jackson Delois , Schuchat Anne , Whitney Cynthia G. 
Published: June 2010

OBJECTIVE:
We conducted a case-control study to evaluate risk factors for invasive pneumococcal disease (IPD) among children who were aged 3 to 59 months in the era of pneumococcal conjugate vaccine (PCV7).

METHODS:
IPD cases were identified through routine surveillance during 2001–2004. We matched a median of 3 control subjects to each case patient by age and zip code. We calculated odds ratios for potential risk factors for vaccine-type and non–vaccine-type IPD by using multivariable conditional logistic regression.

RESULTS:
We enrolled 782 case patients (45% vaccine-type IPD) and 2512 matched control subjects. Among children who received any PCV7, children were at increased risk for vaccine-type IPD when they had underlying illnesses, were male, or had no health care coverage. Vaccination with PCV7 did not influence the risk for non–vaccine-type IPD. Presence of underlying illnesses increased the risk for non–vaccine-type IPD, particularly among children who were not exposed to household smoking. Non–vaccine-type case patients were more likely than control subjects to attend group child care, be male, live in low-income households, or have asthma; case patients were less likely than control subjects to live in households with other children.

CONCLUSIONS:
Vaccination with PCV7 has reduced the risk for vaccine-type IPD that is associated with race and group child care attendance. Because these factors are still associated with non–vaccine-type IPD risk, additional reductions in disparities should be expected with new, higher valency conjugate vaccines.
Smoking Expectancies, Weight Concerns, and Dietary Behaviors in Adolescence
Authors: Cavallo Dana A. , Smith Anne E. , Schepis Ty S. , Desai Rani , Potenza Marc N. , Krishnan-Sarin Suchitra 
Published: June 2010

OBJECTIVE:
The objective of this study was to examine the association of cigarette smoking and weight concerns in adolescents, given that adolescents may begin smoking or have difficulty quitting because of their expectancies of the effects of smoking on body weight.

METHODS:
This study used data from a cross-sectional survey of 4523 Connecticut high school adolescents to assess the influence of gender, smoking intensity, and dietary-restrictive behavior on smoking-related weight concerns.

RESULTS:
Heavy smokers were significantly less likely to engage in healthy dietary restrictions than nonsmokers; however, light smokers did not differ from nonsmokers. Both light and heavy smokers were significantly more likely to engage in unhealthy dietary restriction when compared with nonsmokers. In the model that was used to examine smokers only, heavy smokers were significantly less likely to engage in healthy dietary restriction than light smokers, but smoking level was not associated with unhealthy dietary restrictions. Dietary restrictions are significantly associated with smoking-related weight concerns; however, this seems to be related to type of dietary-restrictive behavior, with greater weight concerns observed only in those smokers who engaged in unhealthy dietary restrictions and not in those who engaged in healthy dietary restrictions or no restrictions.

CONCLUSIONS:
Although limited by its cross-sectional nature, the findings from this large, geographically diverse sample have clinical implications for smoking prevention and cessation interventions in adolescents.
Determinants of Anemia Among Young Children in Rural India
Authors: Pasricha Sant-Rayn , Black James , Muthayya Sumithra , Shet Anita , Bhat Vijay , Nagaraj Savitha , Prashanth N. S. , Sudarshan H. , Biggs Beverley-Ann , Shet Arun S. 
Published: June 2010

OBJECTIVE:More than 75% of Indian toddlers are anemic. Data on factors associated with anemia in India are limited. The objective of this study was to determine biological, nutritional, and socioeconomic risk factors for anemia in this vulnerable age group.METHODS:We conducted a cross-sectional study of children aged 12 to 23 months in 2 rural districts of Karnataka, India. Children were excluded if they were unwell or had received a blood transfusion. Hemoglobin, ferritin, folate, vitamin B12, retinol-binding protein, and C-reactive protein (CRP) levels were determined. Children were also tested for hemoglobinopathy, malaria infection, and hookworm infestation. Anthropometric measurements, nutritional intake, family wealth, and food security were recorded. In addition, maternal hemoglobin level was measured.RESULTS:Anemia (hemoglobin level &lt; 11.0 g/dL) was detected in 75.3% of the 401 children sampled. Anemia was associated with iron deficiency (low ferritin level), maternal anemia, and food insecurity. Children's ferritin levels were directly associated with their iron intake and CRP levels and with maternal hemoglobin level and inversely associated with continued breastfeeding and the child's energy intake. A multivariate model for the child's hemoglobin level revealed associations with log(ferritin level) (coefficient: 1.20; P &lt; .001), folate level (0.05; P &lt; .01), maternal hemoglobin level (0.16; P &lt; .001), family wealth index (0.02; P &lt; .05), child's age (0.05 per month; P &lt; .005), hemoglobinopathy (−1.51; P &lt; .001), CRP level (−0.18; P &lt; .001), and male gender (−0.38; P &lt; .05). Wealth index and food insecurity could be interchanged in this model.CONCLUSIONS:Hemoglobin level was primarily associated with iron status in these Indian toddlers; however, maternal hemoglobin level, family wealth, and food insecurity were also important factors. Strategies for minimizing childhood anemia must include optimized iron intake but should simultaneously address maternal anemia, poverty, and food insecurity.
Cardiovascular Safety of VEGF-Targeting Therapies: Current Evidence and Handling Strategies
Authors: Girardi Fabio , Franceschi Enrico , Brandes Alba A. 
Published: June 2010

Abstract
Treatment with the angiogenesis inhibitors bevacizumab, sunitinib, and sorafenib as single agents or in combination with conventional chemotherapy is becoming a cornerstone of modern anticancer therapy. However, the potential toxicity of these drugs, mainly to the cardiovascular system, is still being investigated. Patient assessment at baseline, of crucial importance in candidates for treatment, involves the evaluation of risk factors and screening for past or present cardiovascular disease. Strict monitoring of treatment-related adverse effects must be conducted in order to allow the early detection of cardiovascular toxicities and their prompt medication. In the present paper, the most frequent cardiovascular toxicities and their underlying mechanisms are investigated, with a view to providing indications for effective patient management.