bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutrino masses in an $$SU(4)\otimes U(1)$$-electroweak model with a scalar decuplet
Authors: Ky N. Anh , Hong Van N. T. , Dinh D. Nguyen , Quang Van P. 
Published: October 2019

Abstract
A neutrino mass model is suggested within an $$SU(4)\otimes U(1)$$SU(4)⊗U(1)-electroweak theory. The smallness of neutrino masses can be guaranteed by a seesaw mechanism realized through Yukawa couplings to a scalar SU(4)-decuplet. In this scheme the light active neutrinos are accompanied by heavy neutrinos, which may have masses at different scales, including those within eV–MeV scales investigated quite intensively in both particle physics and astrophysics/cosmology. The flavour neutrinos are superpositions of light neutrinos and a small fraction of heavy neutrinos with the mixing to be determined by the model’s parameters (Yukawa coupling coefficients or symmetry breaking scales). The distribution shape of the Yukawa couplings can be visualized via a model-independent distribution of the neutrino mass matrix elements derived by using the current experimental data. The absolute values of these Yukawa couplings are able to be determined if the symmetry breaking scales are known, and vice versa. With reference to several current and near future experiments, detectable bounds of these heavy neutrinos at different mass scales are discussed and estimated.
“Fragment of What Will Happen”
Authors: Brouwer Rein 
Published: October 2019

Abstract
The Swedish poet Tomas Tranströmer (1931–2015), winner of the 2011 Nobel Prize in Literature, is known for the perceptive metaphors in his poems “couched in deceptively spare language, crystalline descriptions of natural beauty and explorations of the mysteries of identity and creativity.” Although Tranströmer himself never made a secret of the religious tendency in his work, there is some discussion about the importance of the religious dimension in his poems, which are widely acclaimed in Sweden, a predominately secular country. This article discusses several discourses exploring the religious dimensions of Tranströmer’s poetry, and presents a new approach for understanding the religious and spiritual aspects of his art based on the work of philosopher of religion John D. Caputo. Caputo’s “hauntology” is claimed to be conducive in reading Tranströmer’s poetry as a religious text. A “hauntological” reading of the poetry of Tranströmer interprets the event that is haunting the poems, and suggests a new way of conceiving a religious insight in a work of modern art.
Elio Aristide nella scuola tardoantica: commentari e trattati di retorica
Authors: Miletti Lorenzo 
Published: October 2019

Abstract
The article offers an overview of the testimonies about Aelius Aristides’ reception in the didactic context of the late antique schools of rhetoric. After analysing the major issues relating Aristides’ presence in the rhetorical treatises (Hermogenes, Menander rhetor, the ps.-Aristidean ars), the paper focuses in particular on the (lost) commentaries to his mostly widespread works, namely the Panathenaic and the Platonic orations. From the scholia to these speeches it is possible to obtain some information about how these commentaries were, though the annotations which can be attributed with certainty to specific commentators (Metrophanes, Menander, Athanasius, Sopater, and Zosimus) are scarce. In a last section of the paper, some encomia featuring in Libanius’ epistle 1262 and Synesius’ Dio are discussed as far as they resonate with some remarks on Aristides’ style found in scholia, prolegomena, and in rhetorical treatises.
The brain and eye: Treating cerebral and retinal ischemia through mitochondrial transfer
Authors: Heyck Matt , Bonsack Brooke , Zhang Henry , Sadanandan Nadia , Cozene Blaise , Kingsbury Chase , Lee Jea-Young , Borlongan Cesar V 
Published: October 2019

Stroke remains a devastating disease with limited treatment options, despite our growing understanding of its pathology. While ischemic stroke is traditionally characterized by a blockage of blood flow to the brain, this may coincide with reduced blood circulation to the eye, resulting in retinal ischemia, which may in turn lead to visual impairment. Although effective treatment options for retinal ischemia are similarly scarce, new evidence suggests that deleterious changes to mitochondrial structure and function play a major role in both cerebral and retinal ischemia pathologies. Prior studies establish that astrocytes transfer healthy mitochondria to ischemic neurons following stroke; however, this alone is not enough to significantly mitigate the damage caused by primary and secondary cell death. Thus, stem cell-based regenerative medicine targeting amelioration of ischemia-induced mitochondrial dysfunction via the transfer of functional mitochondria to injured neural cells represents a promising approach to improve stroke outcomes for both cerebral and retinal ischemia. In this review, we evaluate recent laboratory evidence supporting the remedial capabilities of mitochondrial transfer as an innovative stroke treatment. In particular, we examine exogenous stem cell transplants in their potential role as suppliers of healthy mitochondria to neurons, brain endothelial cells, and retinal cells.Impact statementStroke constitutes a global health crisis, yet potent, applicable therapeutic options remain effectively inaccessible for many patients. To this end, stem cell transplants stand as a promising stroke treatment and as an emerging subject of research for cell-based regenerative medicine. This is the first review to synthesize the implications of stem cell-derived mitochondrial transfer in both the brain and the eye. As such, this report carries fresh insight into the commonalities between the two stroke-affected organs. We present the findings of this developing area of research inquiry with the hope that our evaluation may advance the use of stem cell transplants as viable therapeutic alternatives for ischemic stroke and related disorders characterized by mitochondrial dysfunction. Such lab-to-clinic translational advancement has the potential to save and improve the ever increasing millions of lives affected by stroke.
Invasive screening for lower extremity peripheral artery disease: Killing two birds with one stone?
Authors: Celebi Savas , Ozcan Celebi Ozlem , Çetin Serkan , Cetin Elif Hande Ozcan , Diker Erdem , Aydogdu Sinan , Berkalp Berkten , Amasyalı Basri 
Published: October 2019

Objectives There is substantial evidence that the majority of cases of lower extremity peripheral artery disease are undetected. As a result, there is great interest in the detection of lower extremity peripheral artery disease through routine screening. However, routine screening of lower extremity peripheral artery disease is still debated. Methods In our cross-sectional study, we included 200 consecutive patients with symptoms suggestive of angina who were undergoing coronary angiography. Irrespective of intermittent claudication, we subsequently performed peripheral angiography to detect lower extremity peripheral artery disease. The predictors of lower extremity peripheral artery disease were analyzed, and the diagnostic utility of these predictors and their combinations were determined. Additionally, the determinants of the amount of radio-opaque material used and peripheral fluoroscopy time were investigated. Results The overall prevalence of lower extremity peripheral disease was 16%. Being older than 65 years, having coronary artery disease and smoking history remained significant predictors after adjusting for other well-known parameters. Having the combination of age  ≥65 and smoking was associated with a positive predictive value of 50% (likelihood ratio 5.06), and having all of the predictors was associated with a positive predictive value of 100% (likelihood ratio >1000). Conclusions Routine screening for lower extremity peripheral disease patients undergoing coronary angiography may be useful in selected patients.
Cardiac reinnervation affects cardiorespiratory adaptations to exercise training in individuals with heart transplantation
Authors: Ciolac Emmanuel G , Castro Rafael E , Marçal Isabela R , Bacal Fernando , Bocchi Edimar A , Guimarães Guilherme V 
Published: October 2019

Purpose The purpose of this study was to investigate the hemodynamic and cardiorespiratory adaptations to exercise in individuals with heart transplantation with evidence of cardiac reinnervation (cardiac reinnervation group) versus without evidence of cardiac reinnervation (no cardiac reinnervation group). Methods Sedentary individuals with heart transplantation (age = 45.5 ± 2.2 years; time elapsed since surgery = 6.7 ± 0.7 years) were divided into the cardiac reinnervation ( n = 16) and no cardiac reinnervation ( n = 17) groups according to their heart rate response to cardiopulmonary exercise testing. The 24-hour ambulatory blood pressure, carotid-femoral pulse wave velocity, and cardiorespiratory fitness were assessed before and after 12 weeks of a thrice-weekly exercise program (five minutes of warm-up, 30 min of endurance exercise, one set of 10–15 reps in five resistance exercises, and five minutes of cool-down). Results The cardiac reinnervation group had reduced ( p < 0.01) 24-hour systolic/diastolic blood pressure (7/9 mm Hg), daytime systolic/diastolic blood pressure (9/10 mm Hg) and nighttime diastolic blood pressure (6 mm Hg) after training. The no cardiac reinnervation group reduced ( p < 0.05) only 24-hour (5 mm Hg), daytime (5 mm Hg) and nighttime (6 mm Hg) diastolic blood pressure after training. Hourly analysis showed that the cardiac reinnervation group reduced systolic/diastolic blood pressure for 10/21 h, while the no cardiac reinnervation group reduced systolic/diastolic blood pressure for only 3/11 h. The cardiac reinnervation group also improved both maximal oxygen consumption (10.8%) and exercise tolerance (13.4%) after training, but the no cardiac reinnervation group improved only exercise tolerance (9.9%). Pulse wave velocity did not change in both groups. Conclusion There were greater improvements in ambulatory blood pressure and maximal oxygen consumption in the cardiac reinnervation than the no cardiac reinnervation group. These results suggest that cardiac reinnervation associates with hemodynamic and cardiorespiratory adaptations to exercise training in individuals with heart transplantation.
Increased Levels of Hepatocyte Growth Factor in Patients with DIC.
Authors: Kawasugi Kazuo , Noguchi Maho , Tashiro Haruko , Gotoh Moritaka , Shirafuji Naoki , Matsuda Juzo , Kinosita Tadatoshi 
Published: October 2019

Abstract
Injury of endothelial cells has been postulated as an initial trigger of the progression of DIC. Although hepatocyte growth factor (HGF) is a member of endothelium-specific growth factor, the relationship between HGF and DIC has not been described. To investigate the role of HGF, we measured plasma levels of HGF in patients with sepsis-associated (n=20) and acute promyelocytic leukemia (APL)-induced DIC (n=6). Plasma samples from those patients groups were assayed for HGF levels by enzyme-linked immunosorbent assay (ELIZA, TECHNE Corporation, USA). The VEGF levels were determined by one-step sandwich enzyme immunoassay (EIA, Chemicon International, USA).
The thrombin antithrombin complexes (TAT) levels were higher in both DIC patients as reported by others. In the septic patients with DIC, we found significant elevations in HGF levels compared to normal controls. Also, the HGF levels were elevated in the APL patients with DIC. However, we did not find any difference in plasma levels of VEGF in the APL and septic patients with DIC. There was a slight correlation between the TAT and HGF levels in both (septic and APL) patients groups with DIC. These results suggest that plasma levels of HGF may be candidates for a marker of DIC. It appears that HGF may contribute to the severity of DIC.
Sepsis associated DIC APL with DIC Controls (n=10) *(P<0.005) significantly different controls HGF 7949±71230* 11902±10726 846±216pg/ml VEGF 172±7.0 209±35 188±8pg/ml TAT 28.4±17.5* 22.5±15.3* <3 μg/ml
Prognostic Impact of MRD in the Bone Marrow of Children at First Isolated Extramedullary Relapse of ALL.
Authors: Hanzsch Nikola , Eckert Cornelia , Acquaviva Cecile , Fronkova Eva , von Stackelberg Arend , Stadt Udo zur , Schrauder Andre , Trka Jan , Seeger Karl , Henze Guenter , Cave Helene 
Published: October 2019

Abstract
Sensitive quantification of minimal residual disease (MRD) is an established method to assess treatment response in patients with bone marrow (BM) relapse of acute lymphoblastic leukemia (ALL). We have investigated, whether MRD can also determine the tumor load in the BM at cytologically isolated extramedullary (IEM) relapse and can consequently be associated with prognosis in this subgroup.
The extent of sub-cytological BM involvement at relapse diagnosis has been quantified in 53 patients with first relapse in the central nervous system (n=36), and in the testes (n=17) treated in Germany (n=33; 09′94 - 12′03) and Czech Republic (n=9; 10′01 - 04′04), or in France (n=11; 12′90 - 11′03) according to protocols ALL-REZ BFM, or to COOPRALL, respectively. MRD has been sensitively assessed by real-time-quantitative PCR using T-cell-receptor and immunoglobulin gene-rearrangements detected in the extramedullary or initial BM material. Stability of initial clonal markers was confirmed. A MRD-level of <10−4 was measured in 22 patients. Thirty-one patients showed a positive MRD-status: <10−3 - =/>10−4: n=9; <10−2 - =/>10−3: n=12; and >10−2: n=10. MRD-status was not associated with the relevant prognostic parameters sex, time-point of relapse, immunophenotype, and site, whereas it was associated with age at initial diagnosis (p=.057), and BCR/ABL translocation (p=.011). The probability of event-free survival (EFS) at 5 years was .55+/−.15 and the rate of subsequent relapses was 18% in patients without MRD detection at a level of 10−4 compared to .16+/−.10 and 52% in those with =/>10−4 (p(log-rank)=.16 and p=.028 respectively).
Our study reveals a large range of subcytological BM involvement in patients with IEM relapses of ALL. A relation to single prognostic factors and to the relapse rate can be found, but not to EFS.
The study was kindly supported by ‘Deutsche Kinderkrebsstiftung’, Germany, by ‘Kompetenznetz der Paediatrischen Onkologie’, BMBF, Germany; by ‘programme hospitalier de recherche clinique’ (PHRC 2002), France and by GAUK 62/2004, Czech Republic.
Co-Existence of Various Sub-Clones in TEL-AML1 Positive Acute Lymphoblastic Leukemia in Association with Sub-Microscopic Deletion of AML1.
Authors: Toren Amos , Rothman Rachel , Bielorai Bella , Reichart Malka , Amariglio Ninette , Rechavi Gideon , Traktenbrot Luba 
Published: October 2019

Abstract
The TEL/AML1 fusion gene is the most common gene rearrangement in pediatric acute lymphoblastic leukemia (ALL). Although considered to be a low risk leukemia it has a 20% risk of late relapse. The coexistence of different sub clones at diagnosis, based on polymerase chain reaction (PCR) studies of Ig/TCR gene rearrangement, was recently reported in this subtype of ALL. Their different response to chemotherapy may explain the emergence of certain sub clones at relapse, and may serve as a marker for minimal residual disease follow-up.
Several chromosomal rearrangements such as t(9;22), t(8;21), inv(16) and rearrangements of the MLL gene are frequently associated with submicroscopic deletions and some of them have prognostic significance. Such deletions were not reported in t(12;21) positive ALL.
Bone marrow cells from 76 pediatric patients with ALL at diagnosis were analyzed for the presence of the TEL/AML1 fusion gene by interphase fluorescence in situ hybridization (FISH). We used a new system of combined analysis enabling a very large-scale study of the cells of interest with regard to morphology, FISH and immunophenotyping. Fourteen patients were positive for the translocation. Four of them had several sub clones associated with various combinations of additional chromosomal abnormalities. The most striking was an atypical and unexpected hybridization pattern consistent with a submicroscopic deletion of the 5′ region of the AML1 breakpoint (intron2) not previously reported. We describe the use of a larger probe for AML1 (AML1/ETO) to exclude the possibility of insertion of TEL into the AML1 region without breakage and to reduce the false positivity due to optical fusion. This may enable a better monitoring of minimal residual disease in cases with submicroscopic deletion. All patients had some sub-clones with TEL deletion. Other abnormalities included trisomy and tetrasomy 21 as well as double TEL-AML1 fusion.
The analysis of numerous sub-clones at presentation in these patients suggests clonal evolution at an early stage of the disease. These sub-clones may have different sensitivities to chemotherapy, and some of them may reappear at relapse. The frequency of AML1 deletion in t(12;21) in addition to other chromosomal abnormalities, is unknown. The involvement of these findings in the generation of leukemic sub clones, their prognostic significance and role in minimal residual disease follow-up deserves further studies in a large number of patients and a longer follow-up.
Discovery of Genes Involved in Experimental Pre-Leukemia to Leukemia Transition in Mice Using Expression Arrays.
Authors: Entin Igor A. , Kogan Scott C. 
Published: October 2019

Abstract
Acute myeloid leukemia (AML) is characterized by a block in differentiation of myeloid cells accompanied by suppression of normal production of blood cells and dissemination of immature cells from their normal hematopoietic environment. In order to gain insight into the mechanisms governing these features of leukemia, we have examined mRNA expression patterns in transgenic mice that express PML-RARA (associated with human acute promyelocytic leukemia, APL) and BCL2. Such mice represent a model system in which these genetic changes combine to initially arrest differentiation in a pre-leukemic state, with acute leukemia arising only upon the acquisition of additional genetic changes. In the present study we identified the set of genes whose transcription is altered in pre-leukemic and leukemic bone marrow in comparison to bone marrow from normal mice. We generated and analyzed three sets of gene expression data from cDNA microarrays: (1) PRE-LEUKEMIA vs. NORMAL (6600 substances), (2) LEUKEMIA vs. NORMAL (6677 substances) and (3) PRE-LEUKEMIA vs. LEUKEMIA (3762 substances). Greater than 90% of substances showed similar expression in the pre-leukemic and leukemic samples. Sixty unique genes were differentially expressed, in a statistically significant manner, with two-fold or more difference in expression, and presenting in all three datasets. Comparison of these 60 revealed genes to a published human AML expression dataset (Bullinger et al., N Engl J Med, 350:1605, 2004) identified eight genes with the same pattern of expression in our mouse model and in human APL, and four common genes with opposite expression. For mouse pre-leukemia vs. leukemia as compared to all human AMLs vs. APL, the eight genes that showed a similar change were: COL1A2, COL5A2, EIF5A, LAMR1, LGALS1, NOTCH2, SNN, and ACP5. Of particular interest to our laboratory are two genes: LGALS1 and NOTCH2. Among the identified genes the first is most over-expressed, and the second is most under-expressed in human APL. Next, we identified genes in our dataset co-expressed with LGALS1 or NOTCH2 (correlation coefficient >0.85). Among discovered genes were revealed transcription factors (NKX6-1, GTF3A, ZFP95, SOX11, HOXA4 and more), translation factors (EIF3S6, EIF5A, EIF4A1 and more), differentiation factors (RQCD1, NEUROD2, CREBBP/EP300 inhibitory protein 1 and more), oncogenes (Ski, COUP-TF1 and more) and others. We are currently seeking to identify which of these changes may contribute to AML pathogenesis. Gene profiling using such a comparative approach for analysis will allow better understanding of leukemogenesis, and can also be applied for studies of tumor progression in other malignancies.
Gene Expression Profiling Identifies Genes Associated with In Vitro Resistance to Daunorubicin and Cytarabine in Children with De Novo Acute Myelogenous Leukemia (AML) from the Pediatric Oncology Group (POG) Study # 9421.
Authors: Kuo Dennis J. , Lacayo Norman J. , Buck Steven , Yu Ron , Saraiya Chitra , Douglas Lorrie , Weinstein Howard , Chang Myron , Willman Cheryl L. , Tibshirani Robert , Dahl Gary V. , Sikic Branimir , Ravindranath Yaddanapudi 
Published: October 2019

Abstract
Daunorubicin and cytarabine are the most effective chemotherapeutic agents for AML. Using MTT (3,[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assays as an in vitro test for sensitivity to these agents, investigators have found that leukemia cells from pediatric AML patients with Down Syndrome, which are more sensitive to cytarabine than blasts from non-Down Syndrome AML patients, have been associated with an increased ratio of deoxycytidine kinase to cytidine deaminase and an increased level of cystathionine-beta-synthetase [Ge, Jensen, Stout et al. Cancer Res2004; 64, 728–35]. Looking for related findings in non-Down syndrome AML, leukemic blasts from non-Down syndrome children with AML were examined utilizing gene expression profiling and MTT assays. Expression signatures from cDNA arrays were related to the drug sensitivity results to daunorubicin and cytarabine by supervised clustering. These results will then be analyzed to look for relationships to the patient’s clinical outcomes and identify genes that may be potential therapeutic targets for drug resistance reversal.
Bone marrow or blood specimens from 103 patients registered on the Pediatric Oncology Group (POG) protocol 9421 were studied. The diagnostic specimens were tested using MTT assays to measure the IC50 (drug concentration that causes 50% of the cells to die) for both daunorubicin and cytarabine. Samples from ninety-three de novo childhood AML patients were analyzed with a 43,760 element spotted array (containing 41,751 unique genes and expression sequence tags [ESTs]) from the Stanford University Microarray Core Facility. We selected the gene expression profile from 10 samples with the highest and lowest IC50’s for each drug. Then, we used Significance Analysis of Microarrays (SAM) to find significant differences in the gene expression between samples sensitive and resistant to each drug. A cluster of 118 overexpressed genes was associated with resistance to daunorubicin (e.g., BCL6, BAPX1, BCL2A1, MBD2, RAB31 and CDKN1A). A cluster of 24 overexpressed genes was associated with resistance to cytarabine (e.g., RIT1, SH3BP2, BCL2A1, NFKBIA, and PTPRE).
In summary, MTT assays and gene expression profiling have identified genes that correlate with daunorubicin and cytarabine resistance. Study of the relationship among drug resistance patterns, gene expression profiles and clinical outcome may allow us to better predict patients’ prognoses at diagnosis and also can be used to identify novel targets for drug resistance reversal.