bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel single nucleotide polymorphism in the protein tyrosine phosphatase N22 gene (PTPN22) is associated with Type 1 diabetes in a Chinese population
Authors: Pei Z. , Chen X. , Sun C. , Du H. , Wei H. , Song W. , Yang Y. , Zhang M. , Lu W. , Cheng R. , Luo F. 
Published: October 2013

AbstractAimsTo examine single nucleotide polymorphisms in the protein tyrosine phosphatase N22 gene (PTPN22) and to study their association with Type 1 diabetes in a Chinese cohort.MethodsThree hundred and sixty‐four young patients with Type 1 diabetes and 719 healthy children were included in this case‐controlled study. The genotypes of rs1217385, rs2488457 (–1123C>G), rs1217414, rs1217419, rs3765598 and rs2476601 (1858C>T) in the PTPN22 gene were determined using the SNaPshot method. Alleles, genotypes and haplotype frequencies were compared between patients with Type 1 diabetes and healthy control subjects. The association between single nucleotide polymorphisms and clinical traits/autoantibody status was also analysed.ResultsThe single nucleotide polymorphism, rs1217419, located in the second intron of the PTPN22 gene was associated with Type 1 diabetes (odds ratio 1.5, 95% CI 1.14–1.97, P = 0.003). An additional single nucleotide polymorphism, rs1217385, was also associated with Type 1 diabetes; however, the association was secondary to that of rs1217419. The previously reported single nucleotide polymorphism that is associated with Type 1 diabetes (–1123G>C) had only marginal association with Type 1 diabetes in our study. A marginal association was also identified between –1123G>C and glutamic acid decarboxylase autoantibody positivity in patients with Type 1 diabetes. There was no association between the single nucleotide polymorphism 1858C>T and Type 1 diabetes in our studied cohort.ConclusionsOur study confirmed that PTPN22 is a gene that contributes to Type 1 diabetes susceptibility. The primary association occurs with single nucleotide polymorphism rs1217419 and there is clear heterogeneity of the association between PTPTN22 polymorphisms and Type 1 diabetes in a Chinese population compared with other populations.
Obesity paradox in people newly diagnosed with type 2 diabetes with and without prior cardiovascular disease
Authors: Thomas G. , Khunti K. , Curcin V. , Molokhia M. , Millett C. , Majeed A. , Paul S. 
Published: October 2013

AbstractAimTo address the debate on ‘obesity paradox’ in patients with type 2 diabetes mellitus (T2DM) by evaluating the cardiovascular and mortality risks associated with normal and overweight patients compared to obese at diagnosis of diabetes, separately for patients with and without cardiovascular disease (CVD) before diagnosis.MethodsA retrospective study with two study cohorts with/without prior CVD (n = 10237/37272) with complete measures of body mass index (BMI) at diagnosis of T2DM from UK General Practice Research Database. Primary outcomes were long‐term risks of cardiovascular events (CVEs) and all‐cause mortality in patients with normal weight, overweight and obesity at diagnosis.ResultsThe mortality rates per 1000 person‐years in normal weight, overweight and obese patients among patients without prior CVD were 13.1, 8.6 and 6.0, respectively, during 5 years of median follow‐up. For patients with prior CVD, these estimates were 30.1, 21.1 and 15.5, respectively. Among patients without and with prior CVD, normal weight patients had 47% (hazard ratio, HR CI: 1.29, 1.69) and 30% (HR CI: 1.11, 1.53) increased mortality risk respectively compared to obese patients. In the cohort without prior CVD, compared to obese patients, those with normal body weight did not have increased CVE risk. Interactions between age, HbA1c and BMI at diagnosis were observed in both cohorts.ConclusionsAdults with normal weight at the diagnosis of T2DM have significantly higher mortality risk compared to those who are obese, with significant interactions between age, BMI and HbA1c. Elevated cardiovascular risk was not observed in normal weight patients without prior CVD.
Serum uric acid level is associated with the development of microalbuminuria in Korean men
Authors: Oh Chang‐Mo , Park Sung Keun , Ryoo Jae‐Hong 
Published: October 2013

AbstractBackgroundElevated serum uric acid (UA) could be a risk factor for hypertension, type 2 diabetes mellitus and cardiovascular disease. In addition, elevated serum UA may be associated with impaired renal function. However, it is unclear whether elevated serum UA is a cause of microalbuminuria or not. Therefore, we performed a prospective cohort study of the temporal relationship between baseline elevated serum UA and the development of microalbuminuria in Korean men.Design and methodsA microalbuminuria‐free cohort of 1743 healthy Korean men, who had their urine albumin–creatinine ratio (UACR) calculated for a medical check‐up programme in 2005, was followed until 2010. Microalbuminuria was defined as a urine albumin–creatinine ratio between 30 and 300 μg/mg. Cox proportional hazards model was performed.ResultsDuring 5884·6 person‐years of follow‐up, 96 incident cases of microalbuminuria developed between 2006 and 2010. After adjusting for multiple covariates, the hazard ratios (95% confidence intervals) for incident microalbuminuria when comparing the second tertile to the third tertile of serum UA levels vs. the first tertile were 1·52 (0·86–2·70) and 2·27 (1·30–3·98), respectively (Pfor trend = 0.005).ConclusionElevated serum UA level was independent risk factor for the development of microalbuminuria during a 5‐year follow‐up in Korean men.
The real role of prediagnostic high‐density lipoprotein cholesterol and the cancer risk: a concise review
Authors: Vílchez Juan A. , Martínez‐Ruiz Ana , Sancho‐Rodríguez Natalia , Martínez‐Hernández Pedro , Noguera‐Velasco Jose A. 
Published: October 2013

AbstractBackgroundIn several observational and clinical studies, the association between serum cholesterol levels and cancer is still unsettled although serum total cholesterol has been associated with increased mortality from cancer. Moreover, the importance of abnormal levels of serum lipid components as the main features of dyslipidemia and the risk of individual cancers is unclear.The prevalence of dyslipidemia is increasing worldwide but, the precise aetiology of the link between risk of cancer and the behaviour of lipid profile, prior diagnosis, has yet to be determinated. Low levels of high‐density lipoprotein cholesterol (HDL) at baseline of many of the studies analyzed has to be taken into account, and continued low levels of HDL without explanation should be considered by clinicians.AimsThe main aim of this review was to undertake the assessment of the most recent studies implying the lipid profile and cancer risk, and focused on low HDL levels at baseline and follow up, and also analyzing this behaviour on the different cancer types.Material and MethodsA literature search was performed to identify publications. The most recent prospective and case‐control studies with multivariate Cox models were analyzed and also were considered some recent meta‐analyses.Results and ConclusionsThe findings exposed in this review suggest that the association with low HDL levels at baseline of different studies of cancer risk is shared among many types of cancer, and it is mainly linked to obesity and inflammation, suggesting a common pathway.
Students' satisfaction with a dental summer programme and importance of influencing factors for choosing dentistry as their career
Authors: Suen R. P. C. , Lai S. M. L. , Bridges S. , Chu C. H. 
Published: October 2013

AbstractAimTo study the students' satisfaction with the week‐long summer programme and the importance of common influencing factors (IFs) for choosing dentistry as their career.MethodsAnonymous questionnaire was given to all 214 participants in July of 2011 and 2012. Demographic information including gender, age and education level was collected. The students were asked about their satisfaction with the programme with separate ratings for learning experiences, including hands‐on workshops (HOW); clinic observations (CO); problem‐based learning tutorials (PBL); and lectures (L). They also rated the relative importance of the ten common IFs. The Friedman test was used to study the order of their preferences of the programme's activities. The Chi‐square test was used to study the influence of their demographic factors on the importance of the IFs.ResultsA total of 208 students returned their questionnaires. The majority were below the age of 18 (81%), and 44% were studying in an international school. Most of the students (96%) were satisfied with the programme overall. They liked the HOWs and COs more than the PBL tutorials and Ls. ‘Altruism’ and ‘medical/health care career’ were the two most important IFs overall. ‘Altruism’ and ‘past experience with dentist’ were considered more important by those aged 18 or above. ‘Past experience with dentist’ and ‘working with hands’ were considered more important by the international school students.ConclusionsMost participants were satisfied with the summer programme. They preferred practical, skill‐based activities to knowledge‐based activities. The importance of some IFs was associated with age and education system.
Do baseline Cereblon gene expression and IL‐6 receptor expression determine the response to thalidomide–dexamethasone treatment in Multiple myeloma patients?
Authors: Bedewy Ahmed M. L. , EL‐Maghraby Shereen M. 
Published: October 2013

AbstractImmunomodulatory drugs (IMiDs) are key components of treatment for hematologic malignancies, especially multiple myeloma (MM). Cereblon (CRBN) expression was described to be essential for the activity of thalidomide. Furthermore, IMiD binding to CRBN is cytotoxic to multiple myeloma cells and absence of CRBN confers IMiDs resistance. Interleukin‐6 (IL‐6) is a potent pleiotropic cytokine that regulates plasma cell (PC) growth via the IL‐6 receptor (IL‐6R). IL‐6/IL‐6R autocrine activity is implicated in the development and progression of cancers including cervical cancer, prostate cancer, and multiple myeloma. The aim of the study was to evaluate CRBN and IL‐6R expressions and their impact on clinical efficacy of dexamethasone–thalidomide therapy in multiple myeloma (MM) patients, in addition to their association with other clinical and prognostic parameters. Forty‐six newly diagnosed MM patients were enrolled in the study. We measured CRBN expression prior to therapy initiation by real‐time polymerase chain reaction in 46 bone marrow (BM) aspiration samples of patients and controls. In addition, IL‐6R expression was evaluated on BM biopsies of patients and controls by immunohistochemistry (IHC). Twenty‐eight males (60.9%) and 18 females (39.1%) were enrolled. The mean age was 65.11 ± 7.3 yr (range 39–77 yr). Median CRBN expression in 46 BM samples of MM patients was significantly higher than in controls (P < 0.001). Among established prognostic parameters, international staging system (ISS), serum beta‐2‐microglobulin (B2M), and serum albumin correlated reversely with CRBN expression. IL‐6R expression was significantly higher in patients than in controls. IL‐6R expression was significantly associated with response to treatment (P < 0.001), B2M (P = 0.032), and ISS (P = 0.028). Strong intensity expression was associated with low CRBN expression (P = 0.001).In conclusion, CRBN expression may provide a biomarker to predict response to IMiD in patients with MM and its high expression can serve as a marker of good prognosis. Strong IL‐6R expression is associated with poor response to therapy in multiple myeloma patients and may be used as a prognostic marker.
Association between statin use and intracerebral hemorrhage: a systematic review and meta‐analysis
Authors: Lei C. , Wu B. , Liu M. , Chen Y. 
Published: October 2013

Background and purposeAccumulating evidence suggests that statins exert neuroprotective effects, but whether their use affects the outcomes of intracerebral hemorrhage (ICH) remains controversial. Therefore, we performed a systematic review and meta‐analysis to investigate whether statin use before spontaneous ICH affects unfavorable functional outcome or mortality.MethodsWe searched the Cochrane Library, MEDLINE, EMBASE and China National Knowledge Infrastructure databases for studies examining the effects of pre‐ICH statin use on unfavorable functional outcome, mortality or neuroimaging outcomes in consecutively recruited patients with spontaneous ICH, regardless of the duration or dose of statin treatment.ResultsA total of 12 studies were included that examined the effects of pre‐ICH statin use on post‐ICH outcomes in 1652 subjects in the favors pre‐statin group and 5309 in the favors no pre‐ICH statin group. Meta‐analysis of 11 studies suggested that pre‐ICH statin use did not significantly affect mortality across all three time points tested [in‐hospital, 30 days, 90 days; odds ratio (OR) 0.85, 95% confidence interval (CI) 0.70–1.03]. However, meta‐analysis of seven studies showed that pre‐ICH statin use did significantly decrease 90‐day mortality (OR 0.72, 95% CI 0.59–0.88). Meta‐analysis of six studies showed that pre‐ICH statin use was not associated with significant changes in unfavorable functional outcome. Moreover, pre‐ICH statin use did not significantly affect admission hematoma volume (standardized mean difference 7.75, 95% CI −5.59 to 21.09).ConclusionAvailable evidence suggests that statin use before spontaneous ICH does not increase short‐term mortality, unfavorable functional outcome or post‐ICH hematoma volume at admission.
Trajectories of health‐related quality of life in children with epilepsy: A cohort study
Authors: Ferro Mark A. , Camfield Carol S. , Levin Simon D. , Smith Mary Lou , Wiebe Samuel , Zou GuangYong , Speechley Kathy N. 
Published: October 2013

SummaryPurposeLittle is known about subgroups of children with epilepsy who may experience less favorable outcomes over time. The objectives of this study were to document trajectories of health‐related quality of life (HRQL) and to identify predictors of the trajectory group in children with new‐onset epilepsy.MethodsData were obtained from the Health Related Quality of Life in Children with Epilepsy Study, a prospective multisite study of children 4–12 years old with new‐onset epilepsy followed for 24 months. Health‐related quality of life was measured using the Quality of Life in Childhood Epilepsy questionnaire. Trajectories of HRQL were investigated using latent class trajectory modeling. Multinomial logistic regression was used to identify child, parent, and family predictors of HRQL trajectories.Key FindingsA total of 374 families responded at baseline and 283 (76%) completed the study. Five HRQL trajectories were observed: low‐increasing (4%), moderate‐decreasing (12%), moderate‐increasing (22%), high‐increasing (32%), and high‐stable (30%). Many children in the low‐increasing, moderate‐increasing, high‐increasing, and high‐stable had clinically meaningful improvements in HRQL: 82%, 47%, 63%, and 44%, respectively. In contrast, the majority of children in the moderate‐decreasing group (56%) experienced clinically meaningful declines in their HRQL. Factors predicting trajectories were number of antiepileptic drugs prescribed, presence of comorbid behavior or cognitive problems, parent depression, and family functioning and demands.SignificanceResults suggested that children with epilepsy are not homogenous but rather consist of groups with different trajectories and unique predictors of HRQL. Problems associated with child behavior and cognition were the strongest predictors identified. Given that several risk factors are modifiable, it is important to examine these as potential targets within a family‐centered framework to improve HRQL of children with new‐onset epilepsy.
Tonic seizures ofLennox‐Gastaut syndrome: Periictal single‐photon emission computed tomography suggests a corticopontine network
Authors: Intusoma Utcharee , Abbott David F. , Masterton Richard A. J. , Stagnitti Monique R. , Newton Mark R. , Jackson Graeme D. , Freeman Jeremy L. , Harvey A. Simon , Archer John S. 
Published: October 2013

SummaryPurposeLennox‐Gastaut syndrome (LGS) is a severe epileptic disorder with characteristic electroclinical features but diverse etiologies. The shared electroclinical characteristics suggest that common cerebral networks are involved in generating seizures. We sought to reveal these networks by comparing ictal and interictal single‐photon emission computed tomography (SPECT).MethodsWe identified 10 ictal–interictalSPECTpairs from seven patients withLGS(median age 11 years; range 1–38) who were studied during video electroencephalography (EEG)–confirmed tonic seizures. We performed a voxel‐wise comparison of ictal and interictalSPECTstudies across the group. The evolution of blood flow changes was explored by examining early and late injection groups.Key FindingsMedian duration of tonic seizures was 10 s (range 6–29 s), and injection latency from seizure offset was −8 to 48 s. In the early injection group (<10 s; three studies), there was hyperperfusion over pons and cerebellar hemispheres (p < 0.05 cluster corrected family wise error), and hypoperfusion bilaterally over the pericentral region, with a trend toward hyperperfusion over bilateral superior and middle frontal gyri, and lateral parietal cortex. In the late injection group, there was hyperperfusion over midline and lateral cerebellar regions, with hypoperfusion widely over bilateral frontal regions.SignificanceThis study suggests that the tonic seizures ofLGSresult from activity in a network, containing bilateral frontal and parietal association areas and the pons. We postulate that tonic seizures recruit the corticoreticular system, which connects frontal attentional areas to the pontine reticular formation, and is normally responsible for postural tone and orienting behavior.
Protective effect of a direct renin inhibitor in acute murine model of cardiotoxicity and nephrotoxicity
Authors: Rashikh Azhar , Pillai Krishna Kolappa , Najmi Abul Kalam 
Published: October 2013

AbstractThis study aimed to investigate the possible protective effects of aliskiren against doxorubicin (DXR)‐induced cardiorenal injury and to identify the mechanisms involved. Intraperitoneal administration of DXR (15 mg/kg, body weight, as a single dose) caused significant induction in the levels of angiotensin I, caspase‐3, lactate dehydrogenase (LDH), lipid peroxidation malondialdehyde (MDA), urea, and creatinine. Concomitant decline in the levels of albumin and total protein in plasma, reduction in reduced glutathione (GSH), and antiperoxidative enzyme superoxide dismutase (SOD) levels followed by ultrastructural alterations in the myocardial and renal tissues were also observed. Oral administration of aliskiren (100 mg/kg, for a period of 14 days) significantly prevented all these DXR‐induced adverse effects and maintained the rats near to normal status. However, telmisartan (10 mg/kg) pretreatment has shown slight protection in DXR‐induced renal injury as evidenced by broadening of podocyte foot process and narrowing of slit pore diameter. The results of aliskiren were compared with telmisartan which was used as reference in this study. These results suggested that aliskiren has protective effects against acute model of DXR‐induced cardiotoxicity and nephrotoxicity, implying that plasma renin activity plays a role in DXR‐induced cardio‐renal injury.
Spider toxins comprising disulfide‐rich and linear amphipathic domains: a new class of molecules identified in the lynx spider Oxyopes takobius
Authors: Vassilevski Alexander A. , Sachkova Maria Y. , Ignatova Anastasija A. , Kozlov Sergey A. , Feofanov Alexei V. , Grishin Eugene V. 
Published: October 2013

In addition to the conventional neurotoxins and cytotoxins, venom of the lynx spider Oxyopes takobius was found to contain two‐domain modular toxins named spiderines: OtTx1a, 1b, 2a and 2b. These toxins show both insecticidal activity (a median lethal dose against flesh fly larvae of 75 μg·g−1) and potent antimicrobial effects (minimal inhibitory concentrations in the range 0.1–10 μm). Full sequences of the purified spiderines were established by a combination of Edman degradation, mass spectrometry and cDNA cloning. They are relatively large molecules (~ 110 residues, 12.0–12.5 kDa) and consist of two distinct modules separated by a short linker. The N–terminal part (~ 40 residues) contains no cysteine residues, is highly cationic, forms amphipathic α–helical structures in a membrane‐mimicking environment, and shows potent cytolytic effects on cells of various origins. The C–terminal part (~ 60 residues) is disulfide‐rich (five S–S bonds), and contains the inhibitor cystine knot (ICK/knottin) signature. The N–terminal part of spiderines is very similar to linear cytotoxic peptides found in various organisms, whereas the C–terminal part corresponds to the usual spider neurotoxins. We synthesized the modules of OtTx1a and compared their activity to that of full‐length mature toxin produced recombinantly, highlighting the importance of the N–terminal part, which retained full‐length toxin activity in both insecticidal and antimicrobial assays. The unique structure of spiderines completes the range of two‐domain spider toxins.DatabaseThe protein sequences of the spiderines (OtTx) reported in this paper have been submitted to the UniProt Knowledgebase (UniProtKB) under accession numbers P86716–P86719, and the nucleotide sequences encoding OtTx have been submitted to the GenBank under accession numbers JX134894–JX134897.
Long‐term dynamics of mycorrhizal root tips in a loblolly pine forest grown with free‐air CO2 enrichment and soil N fertilization for 6 years
Authors: Pritchard Seth G. , Taylor Benton N. , Cooper Emily R. , Beidler Katilyn V. , Strand Allan E. , McCormack M. Luke , Zhang Siyao 
Published: October 2013

AbstractLarge‐scale, long‐term FACE (Free‐Air CO2 enrichment) experiments indicate that increases in atmospheric CO2 concentrations will influence forest C cycling in unpredictable ways. It has been recently suggested that responses of mycorrhizal fungi could determine whether forest net primary productivity (NPP) is increased by elevated CO2 over long time periods and if forests soils will function as sources or sinks of C in the future. We studied the dynamic responses of ectomycorrhizae to N fertilization and atmospheric CO2 enrichment at the Duke FACE experiment using minirhizotrons over a 6 year period (2005–2010). Stimulation of mycorrhizal production by elevated CO2 was observed during only 1 (2007) of 6 years. This increased the standing crop of mycorrhizal tips during 2007 and 2008; during 2008, significantly higher mortality returned standing crop to ambient levels for the remainder of the experiment. It is therefore unlikely that increased production of mycorrhizal tips can explain the lack of progressive nitrogen limitations and associated increases in N uptake observed in CO2‐enriched plots at this site. Fertilization generally decreased tree reliance on mycorrhizae as tip production declined with the addition of nitrogen as has been shown in many other studies. Annual NPP of mycorrhizal tips was greatest during years with warm January temperatures and during years with cool spring temperatures. A 2 °C increase in average late spring temperatures (May and June) decreased annual production of mycorrhizal root tip length by 50%. This has important implications for ecosystem function in a warmer world in addition to potential for forest soils to sequester atmospheric C.