bluuebunny/crossref_metadata_2025_split huggingface dataset:
Olmsted syndrome: exploration of the immunological phenotype
Authors: Danso-Abeam Dina , Zhang Jianguo , Dooley James , Staats Kim A , Van Eyck Lien , Van Brussel Thomas , Zaman Shari , Hauben Esther , Van de Velde Marc , Morren Marie-Anne , Renard Marleen , Van Geet Christel , Schaballie Heidi , Lambrechts Diether , Tao Jinsheng , Franckaert Dean , Humblet-Baron Stephanie , Meyts Isabelle , Liston Adrian 
Published: May 2013

Abstract

Background
Olmsted syndrome is a rare congenital skin disorder presenting with periorifical hyperkeratotic lesions and mutilating palmoplantar keratoderma, which is often associated with infections of the keratotic area. A recent study identified de novo mutations causing constitutive activation of TRPV3 as a cause of the keratotic manifestations of Olmsted syndrome.

Methods
Genetic, clinical and immunological profiling was performed on a case study patient with the clinical diagnosis of Olmsted syndrome.

Results
The patient was found to harbour a previously undescribed 1718G-C transversion in TRPV3, causing a G573A point mutation. In depth clinical and immunological analysis found multiple indicators of immune dysregulation, including frequent dermal infections, inflammatory infiltrate in the affected skin, hyper IgE production and elevated follicular T cells and eosinophils in the peripheral blood.

Conclusions
These results provide the first comprehensive assessment of the immunological features of Olmsted syndrome. The systemic phenotype of hyper IgE and persistent eosinophilia suggest a primary or secondary role of immunological processes in the pathogenesis of Olmsted syndrome, and have important clinical consequences with regard to the treatment of Olmsted syndrome patients.
ENU-mutagenesis mice with a non-synonymous mutation in Grin1 exhibit abnormal anxiety-like behaviors, impaired fear memory, and decreased acoustic startle response
Authors: Umemori Juzoh , Takao Keizo , Koshimizu Hisatsugu , Hattori Satoko , Furuse Tamio , Wakana Shigeharu , Miyakawa Tsuyoshi 
Published: May 2013

Abstract

Background
The Grin1 (glutamate receptor, ionotropic, NMDA1) gene expresses a subunit of N-methyl-D-aspartate (NMDA) receptors that is considered to play an important role in excitatory neurotransmission, synaptic plasticity, and brain development. Grin1 is a candidate susceptibility gene for neuropsychiatric disorders, including schizophrenia, bipolar disorder, and attention deficit/hyperactivity disorder (ADHD). In our previous study, we examined an N-ethyl-N-nitrosourea (ENU)-generated mutant mouse strain (Grin1
Rgsc174/Grin1
+) that has a non-synonymous mutation in Grin1. These mutant mice showed hyperactivity, increased novelty-seeking to objects, and abnormal social interactions. Therefore, Grin1
Rgsc174/Grin1
+ mice may serve as a potential animal model of neuropsychiatric disorders. However, other behavioral characteristics related to these disorders, such as working memory function and sensorimotor gating, have not been fully explored in these mutant mice. In this study, to further investigate the behavioral phenotypes of Grin1
Rgsc174/Grin1
+ mice, we subjected them to a comprehensive battery of behavioral tests.

Results
There was no significant difference in nociception between Grin1
Rgsc174/Grin1
+ and wild-type mice. The mutants did not display any abnormalities in the Porsolt forced swim and tail suspension tests. We confirmed the previous observations that the locomotor activity of these mutant mice increased in the open field and home cage activity tests. They displayed abnormal anxiety-like behaviors in the light/dark transition and the elevated plus maze tests. Both contextual and cued fear memory were severely deficient in the fear conditioning test. The mutant mice exhibited slightly impaired working memory in the eight-arm radial maze test. The startle amplitude was markedly decreased in Grin1
Rgsc174/Grin1
+ mice, whereas no significant differences between genotypes were detected in the prepulse inhibition (PPI) test. The mutant mice showed no obvious deficits in social behaviors in three different social interaction tests.

Conclusions
This study demonstrated that the Grin1
Rgsc174/Grin1
+ mutation causes abnormal anxiety-like behaviors, a deficiency in fear memory, and a decreased startle amplitude in mice. Although Grin1
Rgsc174/Grin1
+ mice only partially recapitulate symptoms of patients with ADHD, schizophrenia, and bipolar disorder, they may serve as a unique animal model of a certain subpopulation of patients with these disorders.
Delta-like 1 regulates Bergmann glial monolayer formation during cerebellar development
Authors: Hiraoka Yuichi , Komine Okiru , Nagaoka Mai , Bai Ning , Hozumi Katsuto , Tanaka Kohichi 
Published: May 2013

Abstract

Background
Bergmann glia (BG) are unipolar cerebellar astrocytes. The somata of mature BG reside in the Purkinje cell layer and extend radially arranged processes to the pial surface. BG have multiple branched processes, which enwrap the synapses of Purkinje cell dendrites. They migrate from the ventricular zone and align next to the Purkinje cell layer during development. Previously, we reported that Notch1, Notch2, and RBPj genes in the BG play crucial roles in the monolayer formation and morphogenesis of BG. However, it remains to be determined which ligand activates Nocth1 and Notch 2 on BG. Delta-like 1 (Dll1) is a major ligand of Notch receptors that is expressed in the developing cerebellum.

Results
In this study, we used human glial fibrillary acidic protein (hGFAP) promoter-driven Cre-mediated recombination to delete Dll1 in BG. Dll1-conditional mutant mice showed disorganization of Bergmann fibers, ectopic localization of BG in the molecular layer and a reduction in the number of BG.

Conclusion
These results suggest that Dll1 is required for the formation of the BG layer and its morphological maturation, apparently through a Notch1/2-RBPj dependent signaling pathway.
ZBTB33 binds unmethylated regions of the genome associated with actively expressed genes
Authors: Blattler Adam , Yao Lijing , Wang Yao , Ye Zhenqing , Jin Victor X , Farnham Peggy J 
Published: May 2013

Abstract

Background
DNA methylation and repressive histone modifications cooperate to silence promoters. One mechanism by which regions of methylated DNA could acquire repressive histone modifications is via methyl DNA-binding transcription factors. The zinc finger protein ZBTB33 (also known as Kaiso) has been shown in vitro to bind preferentially to methylated DNA and to interact with the SMRT/NCoR histone deacetylase complexes. We have performed bioinformatic analyses of Kaiso ChIP-seq and DNA methylation datasets to test a model whereby binding of Kaiso to methylated CpGs leads to loss of acetylated histones at target promoters.

Results
Our results suggest that, contrary to expectations, Kaiso does not bind to methylated DNA in vivo but instead binds to highly active promoters that are marked with high levels of acetylated histones. In addition, our studies suggest that DNA methylation and nucleosome occupancy patterns restrict access of Kaiso to potential binding sites and influence cell type-specific binding.

Conclusions
We propose a new model for the genome-wide binding and function of Kaiso whereby Kaiso binds to unmethylated regulatory regions and contributes to the active state of target promoters.
Use of a Low-fidelity simulator to improve trans-nasal fibre-optic flexible laryngoscopy in the clinical setting: A randomized, single-blinded, prospective study
Authors: Deutschmann Michael W , Yunker Warren K , Cho John J , Andreassen Meri , Beveridge Shari , Bosch John Douglas 
Published: May 2013

Background Trans-nasal flexible fibre-optic laryngoscopy (TFFL) is an essential skill for otolaryngologists. There is evidence to suggest that simulators help residents acquire procedural skills. The objective of this study was to examine the effect of simulation on endoscopy skill acquistion. Methods A randomized controlled trial was conducted utilizing medical students and junior residents with limited experience in TFFL. Learners all performed a baseline endoscopy and were then randomized to receive either 45 minutes of simulation training or not. Following this, a second endoscopy was performed. Time to adequate visualization of the glottis, the percentage of time adequate visualization of the airway was maintained, and the number of collisions with mucosa were analyzed. Qualitative assessments were also obtained from the learner, patient, and staff laryngologist. Results Time to adequate visualization of the glottis and the number of mucosal collisions were significantly less during the second endoscopy, irrespective of the use of simulation (84.8 sec vs. 68 sec, p < 0.01; 5.0 vs. 3.2, p < 0.01, respectively). Analysis using a two-way ANOVA with interaction established that none of the quantitative measures analyzed in this study improved with the addition of simulation. Conclusion Improvements in time to visualization of the glottis and number of mucosal contacts were seen between the first and second endoscopy irrespective of simulator use. No additional benefit was conferred with the use of a low-fidelity simulator.
Does vasopressor therapy have an indication in hemorrhagic shock?
Authors: Beloncle François , Meziani Ferhat , Lerolle Nicolas , Radermacher Peter , Asfar Pierre 
Published: May 2013

Abstract
This review aimed to answer whether the vasopressors are useful at the early phase of hemorrhagic shock. Data were taken from published experimental studies and clinical trials. Published case reports were discarded. A search of electronic database PubMed was conducted using keywords of hemorrhagic shock, vasopressors, vasoconstrictors, norepinephrine, epinephrine, vasopressin. The redundant papers were not included. We identified 15 experimental studies that compared hemorrhagic shock resuscitated with or without vasopressors, three retrospective clinical studies, and one controlled trial. The experimental and clinical studies are discussed in the clinical context, and their strengths as well as limitations are highlighted. There is a strong rationale for a vasopressor support in severe hemorrhagic shock. However, this should be tempered by the risk of excessive vasoconstriction during such hypovolemic state. The experimental models must be analyzed within their own limits and cannot be directly translated into clinical practice. In addition, because of many biases, the results of clinical trials are debatable. Therefore, based on current information, further clinical trials comparing early vasopressor support plus fluid resuscitation versus fluid resuscitation alone are warranted.
Lumpectomy Plus Tamoxifen With or Without Irradiation in Women Age 70 Years or Older With Early Breast Cancer: Long-Term Follow-Up of CALGB 9343
Authors: Hughes Kevin S. , Schnaper Lauren A. , Bellon Jennifer R. , Cirrincione Constance T. , Berry Donald A. , McCormick Beryl , Muss Hyman B. , Smith Barbara L. , Hudis Clifford A. , Winer Eric P. , Wood William C. 
Published: May 2013

Purpose To determine whether there is a benefit to adjuvant radiation therapy after breast-conserving surgery and tamoxifen in women age ≥ 70 years with early-stage breast cancer. Patients and Methods Between July 1994 and February 1999, 636 women (age ≥ 70 years) who had clinical stage I (T1N0M0 according to TNM classification) estrogen receptor (ER) –positive breast carcinoma treated by lumpectomy were randomly assigned to receive tamoxifen plus radiation therapy (TamRT; 317 women) or tamoxifen alone (Tam; 319 women). Primary end points were time to local or regional recurrence, frequency of mastectomy, breast cancer–specific survival, time to distant metastasis, and overall survival (OS). Results Median follow-up for treated patients is now 12.6 years. At 10 years, 98% of patients receiving TamRT (95% CI, 96% to 99%) compared with 90% of those receiving Tam (95% CI, 85% to 93%) were free from local and regional recurrences. There were no significant differences in time to mastectomy, time to distant metastasis, breast cancer–specific survival, or OS between the two groups. Ten-year OS was 67% (95% CI, 62% to 72%) and 66% (95% CI, 61% to 71%) in the TamRT and Tam groups, respectively. Conclusion With long-term follow-up, the previously observed small improvement in locoregional recurrence with the addition of radiation therapy remains. However, this does not translate into an advantage in OS, distant disease-free survival, or breast preservation. Depending on the value placed on local recurrence, Tam remains a reasonable option for women age ≥ 70 years with ER-positive early-stage breast cancer.
Effects of a Telephone-Delivered Multiple Health Behavior Change Intervention (CanChange) on Health and Behavioral Outcomes in Survivors of Colorectal Cancer: A Randomized Controlled Trial
Authors: Hawkes Anna L. , Chambers Suzanne K. , Pakenham Kenneth I. , Patrao Tania A. , Baade Peter D. , Lynch Brigid M. , Aitken Joanne F. , Meng Xingqiong , Courneya Kerry S. 
Published: May 2013

Purpose Colorectal cancer survivors are at risk for poor health outcomes because of unhealthy lifestyles, but few studies have developed translatable health behavior change interventions. This study aimed to determine the effects of a telephone-delivered multiple health behavior change intervention (CanChange) on health and behavioral outcomes among colorectal cancer survivors. Methods In this two-group randomized controlled trial, 410 colorectal cancer survivors were randomly assigned to the health coaching intervention (11 theory-based telephone-delivered health coaching sessions delivered over 6 months focusing on physical activity, weight management, dietary habits, alcohol, and smoking) or usual care. Assessment of primary (ie, physical activity [Godin Leisure Time Index], health-related quality of life [HRQoL; Short Form–36], and cancer-related fatigue [Functional Assessment of Chronic Illness Therapy Fatigue Scale]) and secondary outcomes (ie, body mass index [kg/m2], diet and alcohol intake [Food Frequency Questionnaire], and smoking) were conducted at baseline and 6 and 12 months. Results At 12 months, significant intervention effects were observed for moderate physical activity (28.5 minutes; P = .003), body mass index (−0.9 kg/m2; P = .001), energy from total fat (−7.0%; P = .006), and energy from saturated fat (−2.8%; P = .016). A significant intervention effect was reported for vegetable intake (0.4 servings per day; P = .001) at 6 months. No significant group differences were found at 6 or 12 months for HRQoL, cancer-related fatigue, fruit, fiber, or alcohol intake, or smoking. Conclusion The CanChange intervention was effective for improving physical activity, dietary habits, and body mass index in colorectal cancer survivors. The intervention is translatable through existing telephone cancer support and information services in Australia and other countries.
Prognostic Score Including Gene Mutations in Chronic Myelomonocytic Leukemia
Authors: Itzykson Raphaël , Kosmider Olivier , Renneville Aline , Gelsi-Boyer Véronique , Meggendorfer Manja , Morabito Margot , Berthon Céline , Adès Lionel , Fenaux Pierre , Beyne-Rauzy Odile , Vey Norbert , Braun Thorsten , Haferlach Torsten , Dreyfus François , Cross Nicholas C.P. , Preudhomme Claude , Bernard Olivier A. , Fontenay Michaela , Vainchenker William , Schnittger Susanne , Birnbaum Daniel , Droin Nathalie , Solary Eric 
Published: May 2013

Purpose Several prognostic scoring systems have been proposed for chronic myelomonocytic leukemia (CMML), a disease in which some gene mutations—including ASXL1—have been associated with poor prognosis in univariable analyses. We developed and validated a prognostic score for overall survival (OS) based on mutational status and standard clinical variables. Patients and Methods We genotyped ASXL1 and up to 18 other genes including epigenetic (TET2, EZH2, IDH1, IDH2, DNMT3A), splicing (SF3B1, SRSF2, ZRSF2, U2AF1), transcription (RUNX1, NPM1, TP53), and signaling (NRAS, KRAS, CBL, JAK2, FLT3) regulators in 312 patients with CMML. Genotypes and clinical variables were included in a multivariable Cox model of OS validated by bootstrapping. A scoring system was developed using regression coefficients from this model. Results ASXL1 mutations (P < .0001) and, to a lesser extent, SRSF2 (P = .03), CBL (P = .003), and IDH2 (P = .03) mutations predicted inferior OS in univariable analysis. The retained independent prognostic factors included ASXL1 mutations, age older than 65 years, WBC count greater than 15 ×109/L, platelet count less than 100 ×109/L, and anemia (hemoglobin < 10 g/dL in female patients, < 11g/dL in male patients). The resulting five-parameter prognostic score delineated three groups of patients with median OS not reached, 38.5 months, and 14.4 months, respectively (P < .0001), and was validated in an independent cohort of 165 patients (P < .0001). Conclusion A new prognostic score including ASXL1 status, age, hemoglobin, WBC, and platelet counts defines three groups of CMML patients with distinct outcomes. Based on concordance analysis, this score appears more discriminative than those based solely on clinical parameters.
Role of HDL Cholesterol and Estimates of HDL Particle Composition in Future Development of Type 2 Diabetes in the General Population: The PREVEND Study
Authors: Abbasi Ali , Corpeleijn Eva , Gansevoort Ron T. , Gans Rijk O. B. , Hillege Hans L. , Stolk Ronald P. , Navis Gerjan , Bakker Stephan J. L. , Dullaart Robin P. F. 
Published: May 2013

Background and Aims:
High-density lipoproteins (HDLs) may directly stimulate β-cell function and glucose metabolism. We determined the relationships of fasting high-density lipoprotein cholesterol (HDL-C), plasma apolipoprotein (apo) A-I and apoA-II, and HDL-C–to–apoA-I and HDL-C–to–apoA-II ratios, as estimates of HDL particle composition, with incident type 2 diabetes mellitus.

Methods:
A prospective study was carried out in the Prevention of Renal and Vascular End-Stage Disease (PREVEND) cohort after exclusion of subjects with diabetes at baseline (n = 6820; age, 28–75 years). The association of HDL-related variables with incident type 2 diabetes was determined by multivariate logistic regression analyses.

Results:
After a median follow-up of 7.7 years, 394 incident cases of type 2 diabetes mellitus were ascertained (5.8%). After adjustment for age, sex, family history of diabetes, body mass index, hypertension, alcohol, and smoking, odd ratios (ORs) for diabetes were 0.55 (95% confidence interval [CI], 0.47–0.64; P &lt; .001), 0.81 (0.71–0.93; P = .002), 0.02 (0.01–0.06; P &lt; .001), and 0.03 (0.01–0.060; P &lt; .001) per 1-SD increase in HDL-C and apoA-I and in the HDL-C–to–apoA-I and the HDL-C–to–apoA-II ratios, respectively. In contrast, apoA-II was not related to incident diabetes (OR = 1.02; 95% CI, 0.90–1.16; P=0.71). The relationships of HDL-C and the ratios of HDL-C to apoA-I and HDL-C to apoA-II remained significant after further adjustment for baseline glucose and triglycerides (ORHDL = 0.74 [95% CI, 0.61–0.88], ORHDL/APO A-I = 0.14 [0.04–0.44], and ORHDL/APOA-II = 0.12 [0.04–0.36]; all P ≤ .001).

Conclusions:
Higher HDL-C, as well as higher HDL-C–to–apoA-I and HDL-C–to–apoA-II ratios are strongly and independently related to a lower risk of future type 2 diabetes.
Altered biometal homeostasis is associated with CLN6 mRNA loss in mouse neuronal ceroid lipofuscinosis
Authors: Kanninen Katja M. , Grubman Alexandra , Caragounis Aphrodite , Duncan Clare , Parker Sarah J. , Lidgerwood Grace E. , Volitakis Irene , Ganio George , Crouch Peter J. , White Anthony R. 
Published: May 2013

Summary
Neuronal ceroid lipofuscinoses, the most common fatal childhood neurodegenerative illnesses, share many features with more prevalent neurodegenerative diseases. Neuronal ceroid lipofuscinoses are caused by mutations in CLN genes. CLN6 encodes a transmembrane endoplasmic reticulum protein with no known function. We characterized the behavioural phenotype of spontaneous mutant mice modeling CLN6 disease, and demonstrate progressive motor and visual decline and reduced lifespan in these mice, consistent with symptoms observed in neuronal ceroid lipofuscinosis patients. Alterations to biometal homeostasis are known to play a critical role in pathology in Alzheimer's, Parkinson's, Huntington's and motor neuron diseases. We have previously shown accumulation of the biometals, zinc, copper, manganese and cobalt, in CLN6 Merino and South Hampshire sheep at the age of symptom onset. Here we determine the physiological and disease-associated expression of CLN6, demonstrating regional CLN6 transcript loss, and concurrent accumulation of the same biometals in the CNS and the heart of presymptomatic CLN6 mice. Furthermore, increased expression of the ER/Golgi-localized cation transporter protein, Zip7, was detected in cerebellar Purkinje cells and whole brain fractions. Purkinje cells not only control motor function, an early symptomatic change in the CLN6 mice, but also display prominent neuropathological changes in mouse models and patients with different forms of neuronal ceroid lipofuscinoses. Whole brain fractionation analysis revealed biometal accumulation in fractions expressing markers for ER, Golgi, endosomes and lysosomes of CLN6 brains. These data are consistent with a link between CLN6 expression and biometal homeostasis in CLN6 disease, and provide further support for altered cation transporter regulation as a key factor in neurodegeneration.
San Francisco Declaration on Research Assessment
Authors: Cagan Ross 
Published: May 2013

Summary
On 16 December 2012, a group of editors and publishers of scholarly journals gathered at the Annual Meeting of The American Society for Cell Biology in San Francisco, CA, USA to discuss current issues related to how the quality of research output is evaluated and how the primary scientific literature is cited. The outcome of the meeting and further discussions is a set of recommendations that is referred to as the San Francisco Declaration on Research Assessment, published in May 2013. Disease Models & Mechanisms (DMM) fully supports this initiative. In concordance with the recommendations of the Declaration, DMM provides impact factor alongside a variety of other journal-based metrics, requests an author contribution statement for all research articles, places no restrictions on the reuse of reference lists, and has no limitation on the number of references in research articles.