bluuebunny/crossref_metadata_2025_split huggingface dataset:
Walking speed, rather than Expanded Disability Status Scale, relates to long-term patient-reported impact in progressive MS
Authors: Bosma LVAE , Kragt JJ , Polman CH , Uitdehaag BMJ 
Published: August 2012

Objective: To study the relationships between 1–2 year changes in well-known physician-rated measurements (Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT)) and the long-term (≥ 5 years) outcome in patient-reported outcome (PRO) measures (Multiple Sclerosis Impact Scale (MSIS-29), Multiple Sclerosis Walking Scale (MSWS-12)) that reflect the patient-perceived impact of disease, in progressive MS. Methods: We selected all progressive patients having at least two complete visits within 1-2 years, from a larger cohort of prospectively-followed MS patients. These were invited for another visit, at least 5 years later, consisting of another series of similar examinations, plus 2 PRO scales: the MSIS-29 and MSWS-12. We explored associations between early changes in physician-rated measurements and the long-term outcome as per the PRO measures. Results: In this study,134 patients fulfilled the selection criteria. We found that early change in T25FW was the only physician-rated change that was significantly related to long-term physical impact experienced by the patient, as was assessed by MSIS-29 (Kruskal-Wallis test: χ2=7.8, p=0.020). Early T25FW change, and to a lesser degree early 9HPT change, were significantly related to the reported long-term walking limitations, as assessed by MSWS-12 (Kruskal-Wallis test: χ2=13.8 and p=0.001 for T25FW, χ2=6.5 and p=0.038 for 9HPT). None of the early physician-rated changes were related to the long-term psychological impact experienced by the patient. Conclusion: Early changes on physician-rated scales do have long-term impact in terms of potentially predictive value of outcomes for groups of patients in progressive MS, regarding walking limitations and more global physical impact. Surprisingly, early change in T25FW, rather than early change in EDSS, was significantly associated with longer-term patient-reported disease impact. Our study data support the value of using early physician-rated examinations in clinical trials in progressive MS.
MS risk genes are transcriptionally regulated in CSF leukocytes at relapse
Authors: Jernås Margareta , Malmeström Clas , Axelsson Markus , Olsson Caroline , Nookaew Intawat , Wadenvik Hans , Zetterberg Henrik , Blennow Kaj , Lycke Jan , Rudemo Mats , Olsson Bob 
Published: August 2012

Background: Infiltrating T-helper cells, cytotoxic T-cells, B-cells and monocytes are thought to mediate the damage to myelin, oligodendrocytes and axons in multiple sclerosis (MS), which results in progressive disability. Objective: The objective of this paper is to explore gene expression profiles of leukocytes in the cerebrospinal fluid (CSF) compartment of MS patients during relapse. Methods: Global gene expression was analyzed by DNA microarray analysis of cells in CSF from MS patients and controls, and verifications were performed with real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Results: Fifty percent of the recently described risk genes for MS and 28% of non-risk genes were differently expressed in MS patients compared to controls (χ2-test, p=7.7 × 10−5). Genes involved in T- and NK-cell processes were up-regulated, and genes involved in processes targeting innate immunity or B-cells were down-regulated in MS. Increased expression of EDN1 and CXCL11 and decreased expression of HMOX1 was verified with real-time PCR and increased expression of CXCL13 was verified with ELISA in CSF. Conclusion: DNA microarray analysis is useful in identifying differently expressed genes in CSF leukocytes, which may be important in MS in vivo. Our findings suggest that many of the risk genes for MS are differently expressed in the disease-mediating leukocytes that penetrate the blood-brain barrier.
Microstructural magnetic resonance imaging of cortical lesions in multiple sclerosis
Authors: Filippi M , Preziosa P , Pagani E , Copetti M , Mesaros S , Colombo B , Horsfield MA , Falini A , Comi G , Lassmann H , Rocca MA 
Published: August 2012

Background: Pathologic and magnetic resonance imaging (MRI) studies have shown that cortical lesions (CLs) are a frequent finding in multiple sclerosis (MS). Objective: To quantify microstructural damage in CLs and normal appearing (NA) cortex in relapse-onset MS patients at different stages of the disease. Methods: Brain double inversion recovery (DIR), diffusion tensor (DT) MRI and 3D T1-weighted scans were acquired from 35 relapsing–remitting (RR) patients, 23 secondary progressive (SP) patients, 12 benign (B) MS patients and 41 healthy controls (HC). Diffusivity values in CLs, cortex, white matter (WM) lesions and normal-appearing white matter (NAWM) were assessed. Results: Compared to HC, MS patients had a significantly lower fractional anisotropy (FA) and higher mean diffusivity (MD) in the cortex and NAWM. CLs had higher FA vs HC cortex and vs patients’ cortex. Compared to RRMS patients, SPMS patients had higher WM lesion volume, higher MD in the cortex, and more severe damage to the NAWM and WM lesions. Compared to SPMS patients, BMS patients had lower MD and FA of CLs. Damage in other compartments was similar between SPMS and BMS patients. Damage in CLs had a high power to discriminate BMS from SPMS (area under the curve: 79–91%), with high specificity (85%), sensitivity (100%) and accuracy (90%). Conclusions: Microstructural imaging features of CLs differ from those of WM lesions and are likely to reflect neuronal damage and microglial activation. The nature and extent of CL damage can be used to help distinguish the different MS clinical phenotypes.
Retinol levels are associated with magnetic resonance imaging outcomes in multiple sclerosis
Authors: Løken-Amsrud Kristin I , Myhr Kjell-Morten , Bakke Søren J , Beiske Antonie G , Bjerve Kristian S , Bjørnarå Bård T , Hovdal Harald , Lilleås Finn , Midgard Rune , Pedersen Tom , Benth Jūratė Šaltytė , Torkildsen Øivind , Wergeland Stig , Holmøy Trygve 
Published: August 2012

Background: Vitamin A has immunomodulatory properties and may regulate the transcription of genes involved in remyelination. Objective: To investigate the association between retinol and disease activity in multiple sclerosis (MS). Methods: Cohort study of 88 relapsing–remitting MS patients, originally included in a randomised placebo-controlled trial of omega-3 fatty acids in MS (the OFAMS study), followed prospectively for 24 months with repeated assessments of serum-retinol and magnetic resonance imaging (MRI). All patients were initiated on interferon β-1a after month 6. Results: Each 1 µmol/L increase in serum-retinol reduced the odds (95% confidence interval) for new T1 gadolinium enhanced (Gd+) lesions by 49 (8–70)%, new T2 lesions by 42 (2–66)%, and combined unique activity (CUA) by 46 (3–68)% in simultaneous MRI scans, and 63 (25–82)% for new T1Gd+ lesions, 49 (3–73)% for new T2 lesions and 43 (12–71)% for CUA the subsequent month. Serum-retinol also predicted new T1Gd+ and T2 lesions six months ahead. The associations were not affected by HLA-DRB1*15, or serum levels of 25-hydroxyvitamin D, eicosapentaenoic acid or docosahexaenoic acid. Conclusion: Serum retinol is inversely associated with simultaneous and subsequent MRI outcomes in RRMS.
IgH partner breakpoint sequences provide evidence that AID initiates t(11;14) and t(8;14) chromosomal breaks in mantle cell and Burkitt lymphomas
Authors: Greisman Harvey A. , Lu Zhengfei , Tsai Albert G. , Greiner Timothy C. , Yi Hye Son , Lieber Michael R. 
Published: August 2012

Abstract
Previous studies have implicated activation-induced cytidine deaminase (AID) in B-cell translocations but have failed to identify any association between their chromosomal breakpoints and known AID target sequences. Analysis of 56 unclustered IgH-CCND1 translocations in mantle cell lymphoma across the ∼ 344-kb bcl-1 breakpoint locus demonstrates that half of the CCND1 breaks are near CpG dinucleotides. Most of these CpG breaks are at CGC motifs, and half of the remaining breaks are near WGCW, both known AID targets. These findings provide the strongest evidence to date that AID initiates chromosomal breaks in translocations that occur in human bone marrow B-cell progenitors. We also identify WGCW breaks at the MYC locus in Burkitt lymphoma translocations and murine IgH-MYC translocations, both of which arise in mature germinal center B cells. Finally, we propose a developmental model to explain the transition from CpG breaks in early human B-cell progenitors to WGCW breaks in later stage B cells.
A novel hierarchical prognostic model of AML solely based on molecular mutations
Authors: Grossmann Vera , Schnittger Susanne , Kohlmann Alexander , Eder Christiane , Roller Andreas , Dicker Frank , Schmid Christoph , Wendtner Clemens-Martin , Staib Peter , Serve Hubert , Kreuzer Karl-Anton , Kern Wolfgang , Haferlach Torsten , Haferlach Claudia 
Published: August 2012

Abstract
The karyotype is so far the most important prognostic parameter in acute myeloid leukemia (AML). Molecular mutations have been analyzed to subdivide AML with normal karyotype into prognostic subsets. The aim of this study was to develop a prognostic model for the entire AML cohort solely based on molecular markers. One thousand patients with cytogenetic data were investigated for the following molecular alterations: PML-RARA, RUNX1-RUNX1T1, CBFB-MYH11, FLT3-ITD, and MLL-PTD, as well as mutations in NPM1, CEPBA, RUNX1, ASXL1, and TP53. Clinical data were available in 841 patients. Based on Cox regression and Kaplan-Meier analyses, 5 distinct prognostic subgroups were identified: (1) very favorable: PML-RARA rearrangement (n = 29) or CEPBA double mutations (n = 42; overall survival [OS] at 3 years: 82.9%); (2) favorable: RUNX1-RUNX1T1 (n = 35), CBFB-MYH11 (n = 31), or NPM1 mutation without FLT3-ITD (n = 186; OS at 3 years: 62.6%); (3) intermediate: none of the mutations leading to assignment into groups 1, 2, 4, or 5 (n = 235; OS at 3 years: 44.2%); (4) unfavorable: MLL-PTD and/or RUNX1 mutation and/or ASXL1 mutation (n = 203; OS at 3 years: 21.9%); and (5) very unfavorable: TP53 mutation (n = 80; OS at 3 years: 0%; P < .001). This comprehensive molecular characterization provides a more powerful model for prognostication than cytogenetics.
Serum activity of DPPIV and its expression on lymphocytes in patients with melanoma and in people with vitiligo
Authors: Matić Ivana Z , Đorđić Marija , Grozdanić Nađa , Damjanović Ana , Kolundžija Branka , Erić-Nikolić Aleksandra , Džodić Radan , Šašić Miomir , Nikolić Srđan , Dobrosavljević Danijela , Rašković Sanvila , Andrejević Slađana , Gavrilović Dušica , Cordero Oscar J , Juranić Zorica D 
Published: August 2012

AbstractBackgroundDipeptidyl peptidase IV, a multifunctional serine protease, is implicated in regulation of malignant transformation, promotion and further progression of cancer, exerting tumor-suppressing or even completely opposite - tumor-promoting activities.The aim of present research was to determine the serum DPPIV activity, as well as the percentages of CD26+ lymphocytes, CD26+ overall white blood cells and the mean fluorescence intensity of CD26 expression on lymphocytes in patients with melanoma, people with vitiligo and in healthy controls.MethodsThe activity of DPPIV in serum was determined by colorimetric test. Expression of DPPIV (as CD26) on immunocompetent peripheral white blood cells was done using flow cytometry analysis.ResultsData from our study show for the first time statistically significant decrease: in the serum DPPIV activity, in the percentage of CD26+ overall white blood cells and in the percentage of lymphocytes in patients with melanoma in comparison to healthy control people. In addition, significantly lower serum DPPIV activity was found in the group of patients with melanoma in relation to people with vitiligo too.ConclusionThis study indicates the need for exploring the cause and the importance of the disturbances in the serum DPPIV activity and in the CD26 expression on immunocompetent cells in complex molecular mechanisms underlying the development and progression of melanoma.
Effect of exercise on chemically-induced colitis in adiponectin deficient mice
Authors: Saxena Arpit , Fletcher Emma , Larsen Bianca , Baliga Manjeshwar Shrinath , Durstine J Larry , Fayad Raja 
Published: August 2012

Abstract

Background
Inflammatory bowel diseases are associated with increased adiponectin (APN) levels, which may exert pro-inflammatory effects in these individuals. Since habitual exercise may increase APN, the aim of this study was to determine how exercise training affects mice with acute colitis.

Methods
Male adiponectin knock out (APNKO) and wild type (WT) mice (C57BL/6) were randomly assigned to 4 different groups: 1) Sedentary (SED); 2) Exercise trained (ET); 3) Sedentary with dextran sodium sulfate (DSS) treatment (SED + DSS); and 4) Exercise trained with DSS (ET + DSS). Exercise-trained mice ran at 18 m/min for 60 min, 5d/wk for 4 weeks. Subsequently, the ET + DSS and the SED + DSS mice received 2% DSS in their drinking water for 5 days (d), followed by 5d of regular water.

Results
The clinical symptoms of acute colitis (diarrhea, stool haemoccult, and weight loss) were unaffected by exercise and there was no difference between the APNKO and WT mice (p > 0.05) except on day 39. However, the clinical symptoms of the DSS-treated APNKO mice were worse than WT mice treated with DSS and had increased susceptibility to intestinal inflammation due to increased local STAT3 activation, higher IL-6, TNF-α, IL-1β and IL-10 levels, and as a result had increased intestinal epithelial cell proliferation (p < 0.05). Exercise training significantly decreased pro-inflammatory cytokines including IL-6, TNF-α and IL-1β (p < 0.05) in the DSS + EX APNKO mice but had no effect on epithelial cell proliferation. Exercise was also found to significantly decrease the phosphorylation expression of STAT3 in both WT and APNKO mice in DSS + EX group when compared to DSS + SED.

Conclusions
Exercise training may contribute in alleviating the symptoms of acute colitis and APN deficiency may exacerbate the intestinal inflammation in DSS-induced colitis.
Platelet-dependent thrombography gives a distinct pattern of in vitro thrombin generation after surgery with cardio-pulmonary bypass: potential implications
Authors: Said Rose , Regnault Véronique , Hacquard Marie , Carteaux Jean-Pierre , Lecompte Thomas 
Published: August 2012

Abstract

Background
Bleeding remains a potentially lethal complication of cardio-pulmonary bypass (CPB) surgery. The purpose of this study was to obtain a better insight into in vitro thrombin generation in the context of CPB.

Methods
We used Calibrated Automated Thrombography to assess blood coagulation of 10 low-risk patients operated for valve replacement with CPB, under 2 experimental conditions, one implicating platelets as platelet dysfunction has been described to occur during CPB.

Results
Our main finding was that CPB-induced coagulopathy was differently appreciated depending on the presence or absence of platelets: the decrease in thrombin generation was much less pronounced in their presence (mean endogenous thrombin potential change values before and after CPB were -3.9% in the presence of platelets and -39.6% in their absence).

Conclusion
Our results show that experimental conditions have a profound effect in the study of in vitro thrombin generation in the context of CPB.
Involvement of Tyr1472 Phosphorylation of NMDA Receptor NR2B Subunit in Postherpetic Neuralgia in Model Mice
Authors: Unezaki Sawako , Sasaki Atsushi , Mabuchi Tamaki , Matsumura Shinji , Katano Tayo , Nakazawa Takanobu , Nishio Naoko , Andoh Tsugunobu , Yamamoto Tadashi , Nakatsuka Terumasa , Kuraishi Yasushi , Ito Seiji 
Published: August 2012

Background: Postherpetic neuralgia is spontaneous pain and allodynia that persist long after the disappearance of the cutaneous lesions caused by herpes zoster. Inoculation of mice with herpes simplex virus-1 causes herpes zoster-like skin lesions and herpetic and postherpetic pain. Although NMDA receptors have been suggested to be involved in postherpetic pain as in other types of neuropathic pain, the neural mechanism remains unclear. NMDA receptor NR2B subunit is the most tyrosine-phosphorylated protein in the brain, and Tyr1472 is the major phosphorylation site of this subunit. Results: To elucidate the role of Tyr1472 phosphorylation of the NR2B subunit in herpetic and postherpetic allodynia, we inoculated herpes simplex virus-1 into the unilateral hind paw of knock-in mice with a mutation of Tyr1472 of the NR2B subunit to Phe (Y1472F-KI). On day 7 post-inoculation, acute herpetic allodynia was observed in more than 80% of the inoculated wild-type and Y1472F-KI mice. Y1472F-KI mice showed significantly reduced intensity and incidence of postherpetic allodynia on days 45–50 post-inoculation as compared with wild-type mice. The innervation in the skin at the postherpetic neuralgia phase was retained to a greater extent in the Y1472F-KI mice. The level of activating transcription factor-3 mRNA, a marker of axonal damage, increased much less in the dorsal root ganglia (DRGs) of Y1472F-KI mice than in those of wild-type mice; and the level of nerve growth factor mRNA significantly increased in wild-type mice, but not at all in Y1472F-KI mice on day 7 post-inoculation. Production of nerve growth factor was at the basal level in the skin of both groups of mice on day 50 post-inoculation. Nerve growth factor and glial cell-derived neurotrophic factor stimulated neurite outgrowth of cultured DRG neurons from Y1472F-KI mice, similarly or less so as they did the outgrowth of those from wild-type mice. Wild-type DRG neurons were more susceptible to glutamate neurotoxicity than Y1472F-KI ones. Conclusions: Taken together, the present data suggest that phosphorylation of the NR2B subunit at its Tyr1472 is involved in the development of postherpetic allodynia due to nerve damage and that the nerve damage at the acute herpetic phase is correlated with the incidence of postherpetic pain.
Effect of metabotropic glutamate receptor 3 genotype on N-acetylaspartate levels and neurocognition in non-smoking, active alcoholics
Authors: Xia Yan , Ma Dongying , Hu Jian , Tang Chunling , Wu Zheng , Liu Lei , Xin Feng 
Published: August 2012

AbstractBackgroundWe studied the effects of single nucleotide polymorphisms (SNPs) in the metabotropic glutamate receptor 3 (GRM3) gene on brain N-acetylaspartate (NAA) concentrations and executive function (EF) skills in non-smoking, active alcoholics, and evaluated associations between these variables.MethodsSNPs (rs6465084, rs1468412, and rs2299225) in GRM3 were genotyped in 49 male, non-smoking, alcohol-dependent patients and 45 healthy control subjects using ligase detection reactions. NAA/creatine (Cr) ratios in left prefrontal gray matter (GM) and white matter (WM), left parietal GM, left parietal WM, and cerebellar vermis regions were measured by Proton1 H Magnetic resonance spectroscopy (MRS). EF was measured by the Wisconsin Card Sorting Test (WCST).ResultsCompared to controls, alcoholics had lower NAA/Cr ratios in prefrontal GM and WM regions and performed more poorly on all EF tests (P < 0.001). Alcoholics with the A/A genotype for SNP rs6465084 had lower NAA/Cr ratios in prefrontal GM and WM regions and had poorer EF skills than alcoholics who were G-carriers for this SNP (P < 0.01). Non-alcoholics with the A/A genotype for rs6465084 also had lower NAA/Cr levels in prefrontal GM and made more random errors in the WCST than G-carriers (P < 0.01). The A/A genotype group for SNP rs6465084 was significantly different from the G carriers for the variables of NAA/Cr ratios and WCST scores in both alcoholics and controls (P < 0.05). Alcoholics who were T-carriers for rs1468412 had lower NAA/Cr ratios in prefrontal GM and showed poorer EF skills (P < 0.05). No effects of rs2299225 genotype on NAA/Cr or executive skills were observed. NAA/Cr in left prefrontal regions correlated with certain parameters of EF testing in both alcoholics and controls (P < 0.05), but the significance of this correlation among alcoholics disappeared after adjustment for the effects of genotype.ConclusionsOur results provide evidence that glutamate system dysfunction may play a role in the prefrontal functional abnormalities seen in alcohol dependence. It is possible that certain GRM3 SNP genotypes (the A/A genotype of rs6465084 and the T allele of rs1468412) may further lower NAA/Cr levels and EF skills in addition to the effect of alcohol.
In-vitro comparison of LC-DCP- and LCP-constructs in the femur of newborn calves – a pilot study
Authors: Hoerdemann Mona , Gédet Philippe , Ferguson Steven J , Sauter-Louis Carola , Nuss Karl 
Published: August 2012

AbstractBackgroundTo compare the biomechanical in-vitro characteristics of limited-contact dynamic compression plate (LC-DCP) and locking compression plate (LCP) constructs in an osteotomy gap model of femoral fracture in neonatal calves. Pairs of intact femurs from 10 calves that had died for reasons unrelated to the study were tested. A 7-hole LC-DCP with six 4.5 mm cortical screws was used in one femur and a 7-hole LCP with four 5.0 mm locking and two 4.5 mm cortical screws was used in the corresponding femur. The constructs were tested to failure by cyclic compression at a speed of 2 mm/s within six increasing force levels.ResultsThe bone-thread interface was stripped in 21 of 80 cortical screws (26.3%) before a pre-set insertion torque of 3 Nm was achieved. Only 3 corresponding intact pairs of constructs could be statistically compared for relative structural stiffness, actuator excursion and width of the osteotomy gap. Relative structural stiffness was significantly greater, actuator excursion and width of the osteotomy gap were significantly smaller in the LCP constructs. While failure occurred by loosening of the screws in the LC-DCP constructs, locking constructs failed by cutting large holes in the soft distal metaphyseal bone.ConclusionsAn insertion torque sufficient to provide adequate stability in femurs of newborn calves could not be achieved reliably with 4.5 mm cortical screws. Another limiting factor for both constructs was the weak cancellous bone of the distal fracture fragment. LCP constructs were significantly more resistant to compression than LC-DCP constructs.