bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intranuclear inclusions in a fragile X mosaic male
Authors: Pretto Dalyir I , Hunsaker Michael R , Cunningham Christopher L , Greco Claudia M , Hagerman Randi J , Noctor Stephen C , Hall Deborah A , Hagerman Paul J , Tassone Flora 
Published: May 2013

AbstractLack of the fragile X mental retardation protein leads to Fragile X syndrome (FXS) while increased levels ofFMR1mRNA, as those observed in premutation carriers can lead to Fragile X- associated tremor ataxia syndrome (FXTAS). Until recently, FXTAS had been observed only in carriers of anFMR1premutation (55–200 CGG repeats); however the disorder has now been described in individuals carriers of an intermediate allele (45–54 CGG repeats) as well as in a subject with a full mutation with mosaicism.Here, we report on molecular and clinical data of a maleFMR1mosaic individual with full and premutation alleles. Molecular analysis ofFMR1and FMRP expression in this subject is consistent with a FXS phenotype. We observed reduced expression of FMRP in both peripheral blood and brain leading to the FXS diagnosis. In addition, a dramatic 90% depletion of bothFMR1mRNA and FMRP levels was observed in the blood, as normally observed in FXS cases, and an even greater depletion in the brain. A clinical report of this patient, at age 71, described neurodegenerative signs of parkinsonism that were likely, in retrospect, part of a FXTAS scenario as post-mortem examination shows the presence of intranuclear inclusions, the hallmark pathology of FXTAS.The findings presented in this study indicate co-morbidity for both FXS and FXTAS in this individual carrying both full and premutationFMR1alleles. In addition, based on symptoms and pathological and molecular evidence, this report suggests the need to redefine the diagnostic criteria of FXTAS.
Treatment with CNX-011-67, a novel GPR40 agonist, delays onset and progression of diabetes and improves beta cell preservation and function in male ZDF rats
Authors: Gowda Nagesh , Dandu Anilkumar , Singh Jaideep , Biswas Sanghamitra , Raghav Vijaya , Lakshmi Mudigere N , Shilpa Pavagada C , Sunil Venkategowda , Reddy Ashokkumar , Sadasivuni Manojkumar , Aparna Kumaraswamy , Verma Mahesh Kumar , Moolemath Yoganand , Anup Mammen O , Venkataranganna Marikunte V , Somesh Baggavalli P , Jagannath Madanahalli R 
Published: May 2013

Abstract

Background
The role of G protein-coupled receptor (GPR40), which is highly expressed in pancreatic beta cells, has been studied extensively in the amelioration of beta cell dysfunction in T2D using rat and mouse islets, beta cell lines and in animal models of diabetes. But its potential as a therapeutic target has not been fully explored. This aim of the study is to evaluate the therapeutic potential of CNX-011-67, a highly selective, potent and orally bioavailable GPR40 agonist, in controlling diabetes and other metabolic parameters.

Methods
Seven week old male ZDF rats were treated with either vehicle or CNX-011-67, 5 mg/kg twice daily, for seven weeks. The animals were subjected to oral glucose tolerance and insulin tolerance tests. Plasma glucose, insulin, triglyceride, HbA1c, fructosamine and free fatty acids were measured at selected time points. Pancreas from control and treated animals were subjected to insulin and pancreatic and duodenal homeobox 1 (PDX1) immunohistochemistry and were also evaluated by electron microscopy. Also the potential impact of CNX-011-67 on islet insulin secretion, content, ATP levels and markers of both glucose oxidation, beta cell health in rat islets under chronic glucolipotoxic conditions was evaluated.

Results
Treatment of male ZDF rats with CNX-011-67 for 7 weeks significantly enhanced insulin secretion in response to oral glucose load, delayed the onset of fasting hyperglycemia by 3 weeks, reduced nonfasting glucose excursions, fasting free fatty acids and triglyceride levels. A significant increase in PDX1 expression and insulin content and reduction in plasma fructosamine, HOMA-IR, and beta cell apoptosis were observed. CNX-011-67 improves glucose mediated insulin secretion, insulin gene transcription and islet insulin content in cultured rat islets under chronic glucolipotoxic condition. Also enhanced glucose oxidation in the form of increased islet ATP content and overall improvement in beta cell health in the form of reduced expression of stress markers (TXNIP and CHOP mRNA) were observed.

Conclusions
These findings, suggest that long-term oral therapy with CNX-011-67 could be of clinical value to provide good glycemic control and improve islet beta cell function.
CD70–CD27 ligation between neural stem cells and CD4+ T cells induces Fas–FasL-mediated T-cell death
Authors: Lee Eun Mi , Hurh Sunghoon , Cho Bumrae , Oh Kook-Hwan , Kim Seung U , Surh Charles D , Sprent Jonathan , Yang Jaeseok , Kim Jae Young , Ahn Curie 
Published: May 2013

Abstract
Introduction
Neural stem cells (NSCs) are among the most promising candidates for cell replacement therapy in neuronal injury and neurodegenerative diseases. One of the remaining obstacles for NSC therapy is to overcome the alloimmune response on NSCs by the host.

Methods
To investigate the mechanisms of immune modulatory function derived from the interaction of human NSCs with allogeneic T cells, we examined the immune regulatory effects of human NSCs on allogeneic T cells in vitro.

Results
Significantly, NSCs induced apoptosis of allogeneic T cells, in particular CD4+ T cells. Interaction of CD70 on NSCs and CD27 on CD4+ T cells mediated apoptosis of T cells. Thus, blocking CD70–CD27 interaction prevented NSC-mediated death of CD4+ T cells.

Conclusions
We present a rational explanation of NSC-induced immune escape in two consecutive stages. First, CD70 constitutively expressed on NSCs engaged CD27 on CD4+ T cells, which induced Fas ligand expression on CD4+ T cells. Second, CD4+ T-cell apoptosis was followed by Fas–Fas ligand interaction in the CD4+ T cells.
Methylphenidate and/or a Nursing Telephone Intervention for Fatigue in Patients With Advanced Cancer: A Randomized, Placebo-Controlled, Phase II Trial
Authors: Bruera Eduardo , Yennurajalingam Sriram , Palmer J. Lynn , Perez-Cruz Pedro E. , Frisbee-Hume Susan , Allo Julio A. , Williams Janet L. , Cohen Marlene Z. 
Published: May 2013

Purpose Cancer-related-fatigue (CRF) is common in advanced cancer. The primary objective of the study was to compare the effects of methylphenidate (MP) with those of placebo (PL) on CRF as measured using the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) fatigue subscale. The effect of a combined intervention including MP plus a nursing telephone intervention (NTI) was also assessed. Patients and Methods Patients with advanced cancer with a fatigue score of ≥ 4 out of 10 on the Edmonton Symptom Assessment Scale (ESAS) were randomly assigned to one of the following four groups: MP+NTI, PL+NTI, MP + control telephone intervention (CTI), and PL+CTI. Methylphenidate dose was 5 mg every 2 hours as needed up to 20 mg per day. The primary end point was the median difference in FACIT-F fatigue at day 15. Secondary outcomes included anxiety, depression, and sleep. Results One hundred forty-one patients were evaluable. Median FACIT-F fatigue scores improved from baseline to day 15 in all groups: MP+NTI (median score, 4.5; P = .005), PL+NTI (median score, 8.0; P < .001), MP+CTI (median score, 7.0; P = .004), and PL+CTI (median score, 5.0; P = .03). However, there were no significant differences in the median improvement in FACIT-F fatigue between the MP and PL groups (5.5 v 6.0, respectively; P = .69) and among all four groups (P = .16). Fatigue (P < .001), nausea (P = .01), depression (P = .02), anxiety (P = .01), drowsiness (P < .001), appetite (P = .009), sleep (P < .001), and feeling of well-being (P < .001), as measured by the ESAS, significantly improved in patients who received NTI. Grade ≥ 3 adverse events did not differ between MP and PL (40 of 93 patients v 29 of 97 patients, respectively; P = .06). Conclusion MP and NTI alone or combined were not superior to placebo in improving CRF.
Phase III Randomized, Placebo-Controlled Study of Cetuximab Plus Brivanib Alaninate Versus Cetuximab Plus Placebo in Patients With Metastatic, Chemotherapy-Refractory, Wild-Type K-RAS Colorectal Carcinoma: The NCIC Clinical Trials Group and AGITG CO.20 Trial
Authors: Siu Lillian L. , Shapiro Jeremy D. , Jonker Derek J. , Karapetis Chris S. , Zalcberg John R. , Simes John , Couture Felix , Moore Malcolm J. , Price Timothy J. , Siddiqui Jehan , Nott Louise M. , Charpentier Danielle , Liauw Winston , Sawyer Michael B. , Jefford Michael , Magoski Nadine M. , Haydon Andrew , Walters Ian , Ringash Jolie , Tu Dongsheng , O'Callaghan Chris J. 
Published: May 2013

Purpose The antiepidermal growth factor receptor monoclonal antibody cetuximab has improved survival in patients with metastatic, chemotherapy-refractory, wild-type K-RAS colorectal cancer. The addition of brivanib, a tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor and fibroblast growth factor receptor, to cetuximab has shown encouraging early clinical activity. Patients and Methods Patients with metastatic colorectal cancer previously treated with combination chemotherapy were randomly assigned 1:1 to receive cetuximab 400 mg/m2 intravenous loading dose followed by weekly maintenance of 250 mg/m2 plus either brivanib 800 mg orally daily (arm A) or placebo (arm B). The primary end point was overall survival (OS). Results A total of 750 patients were randomly assigned (376 in arm A and 374 in arm B). Median OS in the intent-to-treat population was 8.8 months in arm A and 8.1 months in arm B (hazard ratio [HR], 0.88; 95% CI, 0.74 to 1.03; P = .12). Median progression-free survival (PFS) was 5.0 months in arm A and 3.4 months in arm B (HR, 0.72; 95% CI, 0.62 to 0.84; P < .001). Partial responses observed (13.6% v 7.2%; P = .004) were higher in arm A. Incidence of any grade ≥ 3 adverse events was 78% in arm A and 53% in arm B. Fewer patients received ≥ 90% dose-intensity of both cetuximab (57% v 83%) and brivanib/placebo (48% v 87%) in arm A versus arm B, respectively. Conclusion Despite positive effects on PFS and objective response, cetuximab plus brivanib increased toxicity and did not significantly improve OS in patients with metastatic, chemotherapy-refractory, wild-type K-RAS colorectal cancer.
Randomized International Phase III Trial of ERCC1 and RRM1 Expression–Based Chemotherapy Versus Gemcitabine/Carboplatin in Advanced Non–Small-Cell Lung Cancer
Authors: Bepler Gerold , Williams Charles , Schell Michael J. , Chen Wei , Zheng Zhong , Simon George , Gadgeel Shirish , Zhao Xiuhua , Schreiber Fred , Brahmer Julie , Chiappori Alberto , Tanvetyanon Tawee , Pinder-Schenck Mary , Gray Jhanelle , Haura Eric , Antonia Scott , Fischer Juergen R. 
Published: May 2013

Purpose We assessed whether chemotherapy selection based on in situ ERCC1 and RRM1 protein levels would improve survival in patients with advanced non–small-cell lung cancer (NSCLC). Patients and Methods Eligible patients were randomly assigned 2:1 to the trial's experimental arm, which consisted of gemcitabine/carboplatin if RRM1 and ERCC1 were low, docetaxel/carboplatin if RRM1 was high and ERCC1 was low, gemcitabine/docetaxel if RRM1 was low and ERCC1 was high, and docetaxel/vinorelbine if both were high. In the control arm, patients received gemcitabine/carboplatin. The trial was powered for a 32% improvement in 6-month progression-free survival (PFS). Results Of 331 patients registered, 275 were eligible. The median number of cycles given was four in both arms. A tumor rebiopsy specifically for expression analysis was required in 17% of patients. The median time from informed consent to expression analysis was 11 days. We found no statistically significant differences between the experimental arm and the control arm in PFS (6.1 months v 6.9 months) or overall survival (11.0 months v 11.3 months). A subset analysis revealed that patients with low levels for both proteins who received the same treatment in both treatment arms had a statistically better PFS (P = .02) in the control arm (8.1 months) compared with the experimental arm (5.0 months). Conclusion This demonstrates that protein expression analysis for therapeutic decision making is feasible in newly diagnosed patients with advanced-stage NSCLC. A tumor rebiopsy is safe, required in 17%, and acceptable to 89% (47 of 53) of patients.
International Myeloma Working Group Recommendations for the Treatment of Multiple Myeloma–Related Bone Disease
Authors: Terpos Evangelos , Morgan Gareth , Dimopoulos Meletios A. , Drake Matthew T. , Lentzsch Suzanne , Raje Noopur , Sezer Orhan , García-Sanz Ramón , Shimizu Kazuyuki , Turesson Ingemar , Reiman Tony , Jurczyszyn Artur , Merlini Giampaolo , Spencer Andrew , Leleu Xavier , Cavo Michele , Munshi Nikhil , Rajkumar S. Vincent , Durie Brian G.M. , Roodman G. David 
Published: May 2013

PurposeThe aim of the International Myeloma Working Group was to develop practice recommendations for the management of multiple myeloma (MM) –related bone disease.MethodologyAn interdisciplinary panel of clinical experts on MM and myeloma bone disease developed recommendations based on published data through August 2012. Expert consensus was used to propose additional recommendations in situations where there were insufficient published data. Levels of evidence and grades of recommendations were assigned and approved by panel members.RecommendationsBisphosphonates (BPs) should be considered in all patients with MM receiving first-line antimyeloma therapy, regardless of presence of osteolytic bone lesions on conventional radiography. However, it is unknown if BPs offer any advantage in patients with no bone disease assessed by magnetic resonance imaging or positron emission tomography/computed tomography. Intravenous (IV) zoledronic acid (ZOL) or pamidronate (PAM) is recommended for preventing skeletal-related events in patients with MM. ZOL is preferred over oral clodronate in newly diagnosed patients with MM because of its potential antimyeloma effects and survival benefits. BPs should be administered every 3 to 4 weeks IV during initial therapy. ZOL or PAM should be continued in patients with active disease and should be resumed after disease relapse, if discontinued in patients achieving complete or very good partial response. BPs are well tolerated, but preventive strategies must be instituted to avoid renal toxicity or osteonecrosis of the jaw. Kyphoplasty should be considered for symptomatic vertebral compression fractures. Low-dose radiation therapy can be used for palliation of uncontrolled pain, impending pathologic fracture, or spinal cord compression. Orthopedic consultation should be sought for long-bone fractures, spinal cord compression, and vertebral column instability.
Healthy human CSF promotes glial differentiation of hESC-derived neural cells while retaining spontaneous activity in existing neuronal networks
Authors: Kiiski Heikki , Äänismaa Riikka , Tenhunen Jyrki , Hagman Sanna , Ylä-Outinen Laura , Aho Antti , Yli-Hankala Arvi , Bendel Stepani , Skottman Heli , Narkilahti Susanna 
Published: May 2013

Summary
The possibilities of human pluripotent stem cell-derived neural cells from the basic research tool to a treatment option in regenerative medicine have been well recognized. These cells also offer an interesting tool for in vitro models of neuronal networks to be used for drug screening and neurotoxicological studies and for patient/disease specific in vitro models. Here, as aiming to develop a reductionistic in vitro human neuronal network model, we tested whether human embryonic stem cell (hESC)-derived neural cells could be cultured in human cerebrospinal fluid (CSF) in order to better mimic the in vivo conditions. Our results showed that CSF altered the differentiation of hESC-derived neural cells towards glial cells at the expense of neuronal differentiation. The proliferation rate was reduced in CSF cultures. However, even though the use of CSF as the culture medium altered the glial vs. neuronal differentiation rate, the pre-existing spontaneous activity of the neuronal networks persisted throughout the study. These results suggest that it is possible to develop fully human cell and culture-based environments that can further be modified for various in vitro modeling purposes.
Isotope incorporation in broad-snouted caimans (crocodilians)
Authors: Caut Stephane 
Published: May 2013

Summary
The trophic ecology and migration of vertebrate species have been increasingly studied using stable isotope analysis. However, this approach requires knowledge on how dietary isotopic values are reflected in consumers' tissues. To date, this information has only been obtained for a handful of ectotherms; in particular, little is known about crocodilians. In this study, diet-tissue discrimination factors (DTDFs) and carbon and nitrogen stable isotope turnover rates were estimated for plasma, red blood cells (RBCs), and muscle obtained from broad-snouted caimans (Caiman latirostris). Individuals were fed two different control diets for 189 days. DTDFs for δ15N (Δ15N) and δ13C (Δ13C) ranged from −2.24‰ to 0.39‰ and from −0.52‰ to 1.06‰, respectively. Isotope turnover rates in tissues, expressed as half-lives, ranged from 11 to 71 days, with plasma&lt;muscle&lt;RBCs. Δ15N was found to be particularly small, even when compared to values found for other ectotherms, a result that may be linked to the unique excretion physiology of crocodilians. These stable isotope incorporation data should help inform future interpretations of isotopic values obtained in the field for this taxon.
Anomalous Ligand Acceleration on Cinchona-modified Pd/C during Asymmetric Hydrogenation of Properly Substituted Phenylcinnamic Acid
Authors: Ogawa Hiroyuki , Mameda Takuya , Misaki Tomonori , Okamoto Yasuaki , Sugimura Takashi 
Published: May 2013

Abstract
The hydrogenation of 4,4′-dimethoxy-α-phenylcinnamic acid over Pd/C showed a large ligand acceleration effect when a cinchonidine modifier was used; the hydrogen rate increased to 370% relative to the reaction rate on unmodified Pd/C and resulted in a 91% enantiomeric excess (ee). Another good substrate, 4-fluoro-2′-methoxyphenylcinnamic acid, also resulted in a high ee value of 92%; however, the rate increased only to 230% when this modifier was used. On the basis of the difference in the degree to which the reaction rate was accelerated, the eemax for each substrate was analyzed.
1,4-Addition Reaction of 5H-Oxazol-4-ones to Allenic Esters and Ketones Catalyzed by Chiral Guanidines
Authors: Jin Nari , Misaki Tomonori , Sugimura Takashi 
Published: May 2013

Abstract
In this paper, a chiral guanidine-catalyzed 1,4-addition reaction of 5H-oxazol-4-ones to allenic esters and ketones is described. 5H-Oxazol-4-ones substituted with a 2-chlorophenyl group were suitable pronucleophiles that gave high enantioselectivities. Subsequent hydrolysis of the obtained adduct gave the corresponding γ-butenolide ester without loss of enantiopurity and was transformed into (+)-crobarbatic acid in a few steps.
1:1 Co-crystallisation of 1,2,4,5-benzenetetracarboxylic acid (LH4) with isomeric 2,2′-dipyridyldisulfide (2-PA) and 4,4′-dipyridyldisulfide (4-PA)
Authors: Arman Hadi D. , Tiekink Edward R. T. 
Published: May 2013

Abstract
The 1 : 1 co-crystallisation experiments conducted between 1,2,4,5-benzenetetracarboxylic acid, LH4, and each of 2,2′-dipyridyldisulfide (2-PA) and 4,4′-dipyridyldisulfide (4-PA) resulted in the formation of two salts of distinct formulation, i.e. [LH4]0.5[2-PAH][LH3] (1) and [LH2][4-PAH2] (2), respectively, indicating that proton transfer had occurred during crystallisation. In 1, a framework structure constructed by hydrogen bonded (O—H … O) LH4 and LH3
-0 species defines channels in which reside 2-PAH cations that feature syn geometries and intramolecular N—H … N hydrogen bonds. By contrast, in 2, direct N—H … N links between cations and anions lead to zigzag supramolecular chains.
Direct Methanol Fuel Cell – Alternative Materials and Catalyst Preparation
Authors: Mitzel Jens , Arena Francesco , Walter Tanja , Stefener Manfred , Hempelmann Rolf 
Published: May 2013

Abstract
The direct methanol fuel cell is the most interesting fuel cell for mobile applications. The state-of-the-art materials in a practical direct methanol fuel cell are Nafion 115 as membrane, carbon black as catalyst support and PtRu and Pt, respectively, as electrocatalyst. However, many materials were under investigation as alternatives to these materials in the last two decades. The most promising materials are reviewed in this paper. In addition, the catalyst preparation methods are summarized for chemical and electrochemical methods separately. Furthermore, a new electrodeposition technique with a gel-type electrolyte is highlighted. By the use of this method, the catalyst loading on the cathode side can be reduced by 25%.
Health of Children Classified as Underweight by CDC Reference but Normal by WHO Standard
Authors: Meyers Alan , Joyce Katherine , Coleman Sharon M. , Cook John T. , Cutts Diana , Ettinger de Cuba Stephanie , Heeren Timothy C. , Rose-Jacobs Ruth , Black Maureen M. , Casey Patrick H. , Chilton Mariana , Sandel Megan , Frank Deborah A. ,   on behalf of Children’s HealthWatch
Published: May 2013

OBJECTIVE:To ascertain measures of health status among 6- to 24-month-old children classified as below normal weight-for-age (underweight) by the Centers for Disease Control and Prevention (CDC) 2000 growth reference but as normal weight-for-age by the World Health Organization (WHO) 2006 standard.METHODS:Data were gathered from children and primary caregivers at emergency departments and primary care clinics in 7 US cities. Outcome measures included caregiver rating of child health, parental evaluation of developmental status, history of hospitalizations, and admission to hospital at the time of visit. Children were classified as (1) not underweight by either CDC 2000 or WHO 2006 criteria, (2) underweight by CDC 2000 but not by WHO 2006 criteria, or (3) underweight by both criteria. Associations between these categories and health outcome measures were assessed by using multiple logistic regression analysis.RESULTS:Data were available for 18 420 children. For each health outcome measure, children classified as underweight by CDC 2000 but normal by WHO 2006 had higher adjusted odds ratios (aORs) of adverse health outcomes than children not classified as underweight by either; children classified as underweight by both had the highest aORs of adverse outcomes. For example, compared with children not underweight by either criteria, the aORs for fair/poor health rating were 2.54 (95% confidence interval: 2.20–2.93) among children underweight by CDC but not WHO and 3.76 (3.13–4.51) among children underweight by both.CONCLUSIONS:Children who are reclassified from underweight to normal weight in changing from CDC 2000 to WHO 2006 growth charts may still be affected by morbidities associated with underweight.