bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of Seasonal Atlantic Basin Accumulated Cyclone Energy from 1 July
Authors: Klotzbach Philip J. 
Published: October 2013

Abstract
The Tropical Meteorology Project at Colorado State University currently issues seasonal forecasts for Atlantic basin hurricane activity in early April, June, and August. This paper examines the potential for issuing an additional seasonal forecast on 1 July, using a two-predictor forecast model. The two predictors are selected from the ECMWF Interim Re-Analysis (ERA-Interim) and explain over 60% of the cross-validated variance in post–30 June accumulated cyclone energy over the hindcast period from 1979 to 2012. The two predictors selected are May–June-averaged 2-m temperatures in the eastern tropical and subtropical Atlantic along with May–June 200-mb zonal winds in the tropical Indian Ocean. The May–June-averaged 2-m temperatures are shown to strongly correlate with August–October 2-m temperatures in the main development region, while the 200-mb zonal wind flow over the tropical Indian Ocean is shown to strongly correlate with El Niño–Southern Oscillation. In addition, each predictor is shown to correlate significantly with accumulated cyclone energy, both during the hindcast period of 1979–2012 and with an independent period from 1948 to 1978.
Functional examination of MLH1, MSH2, and MSH6 intronic mutations identified in Danish colorectal cancer patients
Authors: Petersen Sanne M , Dandanell Mette , Rasmussen Lene J , Gerdes Anne-Marie , Krogh Lotte N , Bernstein Inge , Okkels Henrik , Wikman Friedrik , Nielsen Finn C , Hansen Thomas v O 
Published: October 2013

Abstract

Background
Germ-line mutations in the DNA mismatch repair genes MLH1, MSH2, and MSH6 predispose to the development of colorectal cancer (Lynch syndrome or hereditary nonpolyposis colorectal cancer). These mutations include disease-causing frame-shift, nonsense, and splicing mutations as well as large genomic rearrangements. However, a large number of mutations, including missense, silent, and intronic variants, are classified as variants of unknown clinical significance.

Methods
Intronic MLH1, MSH2, or MSH6 variants were investigated using in silico prediction tools and mini-gene assay to asses the effect on splicing.

Results
We describe in silico and in vitro characterization of nine intronic MLH1, MSH2, or MSH6 mutations identified in Danish colorectal cancer patients, of which four mutations are novel. The analysis revealed aberrant splicing of five mutations (MLH1 c.588 + 5G > A, MLH1 c.677 + 3A > T, MLH1 c.1732-2A > T, MSH2 c.1276 + 1G > T, and MSH2 c.1662-2A > C), while four mutations had no effect on splicing compared to wild type (MLH1 c.117-34A > T, MLH1 c.1039-8 T > A, MSH2 c.2459-18delT, and MSH6 c.3439-16C > T).

Conclusions
In conclusion, we classify five MLH1/MSH2 mutations as pathogenic, whereas four MLH1/MSH2/MSH6 mutations are classified as neutral. This study supports the notion that in silico prediction tools and mini-gene assays are important for the classification of intronic variants, and thereby crucial for the genetic counseling of patients and their family members.
Antioxidant and pro-oxidant effects of oil palm (Elaeis guineensis) leaves extract in experimental diabetic nephropathy: a duration-dependent outcome
Authors: Varatharajan Rajavel , Sattar Munavvar Zubaid Abdul , Chung Ivy , Abdulla Mahmood Ameen , Kassim Normadiah M , Abdullah Nor Azizan 
Published: September 2013

AbstractBackgroundCatechins-rich oil palm (Elaeis guineensis) leaves extract (OPLE) is known to have antioxidant activity. Several polyphenolic compounds reported as antioxidants such as quercetin, catechins and gallic acid have been highlighted to have pro-oxidant activity at high doses. Therefore, the present study was conducted to investigate the antioxidant and pro-oxidant effects of chronically administering high dose of OPLE (1000 mg kg-1) in an animal model of diabetic nephropathy (DN).MethodsAnimal body weight, indexes of glycaemia, renal function and morphology were assessed in diabetic animals with and without OPLE (1000 mg kg-1) for 4 and 12 weeks respectively. Oxidative stress was quantified by measuring levels of 8-hydroxy-2’-deoxyguanosine (8-OHdG), lipid peroxides (LPO) and reduced glutathione (GSH). Transforming growth factor-beta1 (TGF-β1), a key mediator of extracellular matrix accumulation, was analysed in plasma. The mechanisms of OPLE action were evaluated by assessing nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits (p22phox and p67phox) expression.ResultsOral administration with high dose of catechins-rich OPLE (1000 mg kg-1) to STZ-induced diabetic rats for 4 weeks attenuated renal dysfunction (hyperfiltration, proteinuria) and development of glomerulosclerosis and tubulointerstitial fibrosis, features that are associated with DN. Suppression of increases in oxidative stress markers (8-OHdG, LPO) and the fibrotic cytokine, TGF-β1 was observed. OPLE also reduced renal expression of NADPH oxidase subunits p22phox and p67phox. In contrast and surprisingly, identical dose of OPLE when administered to diabetic animals for 12 weeks caused worsening of renal dysfunction, histopathology in addition to further elevation of oxidative stress marker (LPO) and TGF-β1. These unfavourable effects of prolonged treatment with 1000 mg kg-1OPLE were accompanied by increase expression of one of the NADPH oxidase subunits, p22phox.ConclusionOur study indicates that chronic administration of 1000 mg kg-1OPLE exerts both antioxidant and pro-oxidant effects in DN depending on the duration of treatment. The present study also reveals that the antioxidant/pro-oxidant effects of OPLE are in part, due to modulation of NADPH activity.
Entada africana fraction CH2Cl2/MEOH 5% inhibits inducible nitric oxide synthase and pro-inflammatory cytokines gene expression induced by lipopolysaccharide in microglia
Authors: Owona Brice Ayissi , Njayou Nico Frederic , Laufer Stefan A , Schluesener Hermann J , Moundipa Paul Fewou 
Published: October 2013

Abstract

Background
Inflammatory response in the CNS mediated by microglia cells play an important role in host defense and is implicated in the pathology of neurodegenerative diseases. We investigated the capacity of Entada africana to protect microglia from inflammatory insults by exploring the effect of the CH2Cl2/MEOH 5% fraction (Ea5) on pro-inflammatory cytokines mRNA expression. Finally, we studied the effect of Ea5 on the inhibition of p38 MAPK Kinase. The results were compared to those obtained with Baicalin, a well reported anti-inflammatory flavonoid.

Methods
Barks from E. africana were harvested in 2010, in the west region of Cameroon. A crude extract was prepared using CH2Cl2/MEOH 1:1 V/V. The crude extract obtained was further fractionated by flash chromatography. A mouse microglia cell line (N9) was stimulated by LPS with or without different concentrations of Baicalin and Ea5. The release of NO was evaluated using the Griess method. The expression of pro-inflammatory cytokines mRNA (TNFα, IL-1β, IL-6) and iNOS/NO were measured by RT- PCR. The inhibition of p38 MAPK Kinase was assessed using ELISA.

Results
We found that Ea5, as well as Baicalin inhibited LPS-induced NO production in a dose dependent manner. Ea5 was most active in term of NO inhibition (87.07%), in comparison to Baicalin (70.85%). The expression of TNFα, IL-1β, IL-6 and iNOS was strongly suppressed by Ea5 in microglia. Ea5 also inhibited the activity of p38MAPK Kinase, up to 30% for the concentrations tested, whereas a prominent inhibition was obtained with Baicalin.

Conclusion
These results suggest that E. africana may contain promising compounds useful for the treatment of diseases cause by over-activation of microglia such as Alzheimer disease and other neurological diseases.
Preference-based Health status in a German outpatient cohort with multiple sclerosis
Authors: Reese Jens Peter , Wienemann Gabriele , John Axel , Linnemann Alexandra , Balzer-Geldsetzer Monika , Mueller Ulrich Otto , Eienbröker Christian , Tackenberg Björn , Dodel Richard 
Published: October 2013

Abstract

Background
To prospectively determine health status and health utility and its predictors in patients with multiple sclerosis (MS).

Methods
A total of 144 MS patients (mean age: 41.0 ±11.3y) with different subtypes (patterns of progression) and severities of MS were recruited in an outpatient university clinic in Germany. Patients completed a questionnaire at baseline (n = 144), 6 months (n = 65) and 12 months (n = 55). Health utilities were assessed using the EuroQol instrument (EQ-5D, EQ VAS). Health status was assessed by several scales (Expanded Disability Severity Scale (EDSS), Modified Fatigue Impact Scale (M-FIS), Functional Assessment of MS (FAMS), Beck Depression Inventory (BDI-II) and Multiple Sclerosis Functional Composite (MSFC)). Additionally, demographic and socioeconomic parameters were assessed. Multivariate linear and logistic regressions were applied to reveal independent predictors of health status.

Results
Health status is substantially diminished in MS patients and the EQ VAS was considerably lower than that of the general German population. No significant change in health-status parameters was observed over a 12-months period. Multivariate analyses revealed M-FIS, BDI-II, MSFC, and EDSS to be significant predictors of reduced health status. Socioeconomic and socio-demographic parameters such as working status, family status, number of household inhabitants, age, and gender did not prove significant in multivariate analyses.

Conclusion
MS considerably impairs patients’ health status. Guidelines aiming to improve self-reported health status should include treatment options for depression and fatigue. Physicians should be aware of depression and fatigue as co-morbidities. Future studies should consider the minimal clinical difference when health status is a primary outcome.
Aromatase inhibitor treatment with an intravaginal device and its effect on pre-ovulatory ovarian follicles in a bovine model
Authors: Yapura Jimena , Mapletoft Reuben J , Pierson Roger A , Singh Jaswant , Adams Gregg P 
Published: October 2013

Abstract

Background
Letrozole, a non-steroidal aromatase inhibitor, prevents the body from producing its own estrogen. The objectives of the present study were to test the hypotheses that letrozole treatment, initiated prior to selection of the preovulatory dominant follicle, will induce the growth of more than one follicle to a pre-ovulatory size, and will delay ovulation.

Methods
Post-pubertal beef heifers were given two luteolytic doses of PGF (12 h apart) and monitored by ultrasonography for ovulation. Five to eight days later, ovarian follicular wave emergence was synchronized by ultrasound-guided transvaginal follicular ablation (Day 0=wave emergence) and a luteolytic dose of PGF was given 60 and 72 h later. On Day 1, heifers were divided randomly into two groups (n=15/group) and an intravaginal device containing 1 g of letrozole or a blank device (control) was inserted. The intravaginal devices were removed on Day 7, or at the time of ovulation, whichever occurred first. Transrectal ultrasonography and blood sample collection were performed daily from the day of ablation to 12 days after subsequent ovulation.

Results
The mean (+/-SEM) interval from device placement to ovulation was longer in letrozole-treated animals compared to controls (6.1+/-0.25 vs 5.1+/-0.26 days, respectively; P<0.01). Single dominant follicles were present in both groups. The day-to-day diameter profiles of the dominant follicles of the ovulatory wave were larger (P<0.05) and the maximum diameters greater in letrozole-treated heifers (14.6+/-0.51 vs 12.4+/-0.53 mm, respectively; P<0.01). The diameter profile of the corpus luteum (CL) that formed after treatment did not differ between groups; however, plasma progesterone concentrations were higher (P<0.01) in heifers treated with letrozole. Estradiol concentrations were reduced following letrozole treatment (P<0.05), although a preovulatory rise of estradiol occurred in both groups.

Conclusions
Administration of letrozole with an intravaginal device during growth of the ovulatory follicle delayed ovulation by 24 h and resulted in the formation of a CL that secreted higher levels of progesterone. A sustained-release intravaginal device may be useful for the development of an aromatase inhibitor-based protocol to control ovulation for herd synchronization and to enhance fertility by increasing circulating progesterone concentrations during the first 7 days post-ovulation in cattle.
The proteases HtrA2/Omi and UCH-L1 regulate TNF-induced necroptosis
Authors: Sosna Justyna , Voigt Susann , Mathieu Sabine , Kabelitz Dieter , Trad Ahmad , Janssen Ottmar , Meyer-Schwesinger Catherine , Schütze Stefan , Adam Dieter 
Published: October 2013

Abstract

Background
In apoptosis, proteolysis by caspases is the primary mechanism for both initiation and execution of programmed cell death (PCD). In contrast, the impact of proteolysis on the regulation and execution of caspase-independent forms of PCD (programmed necrosis, necroptosis) is only marginally understood. Likewise, the identity of the involved proteases has remained largely obscure. Here, we have investigated the impact of proteases in TNF-induced necroptosis.

Results
The serine protease inhibitor TPKC protected from TNF-induced necroptosis in multiple murine and human cells systems whereas inhibitors of metalloproteinases or calpain/cysteine and cathepsin proteases had no effect. A screen for proteins labeled by a fluorescent TPCK derivative in necroptotic cells identified HtrA2/Omi (a serine protease previously implicated in PCD) as a promising candidate. Demonstrating its functional impact, pharmacological inhibition or genetic deletion of HtrA2/Omi protected from TNF-induced necroptosis. Unlike in apoptosis, HtrA2/Omi did not cleave another protease, ubiquitin C-terminal hydrolase (UCH-L1) during TNF-induced necroptosis, but rather induced monoubiquitination indicative for UCH-L1 activation. Correspondingly, pharmacologic or RNA interference-mediated inhibition of UCH-L1 protected from TNF-induced necroptosis. We found that UCH-L1 is a mediator of caspase-independent, non-apoptotic cell death also in diseased kidney podocytes by measuring cleavage of the protein PARP-1, caspase activity, cell death and cell morphology. Indicating a role of TNF in this process, podocytes with stably downregulated UCH-L1 proved resistant to TNF-induced necroptosis.

Conclusions
The proteases HtrA2/Omi and UCH-L1 represent two key components of TNF-induced necroptosis, validating the relevance of proteolysis not only for apoptosis, but also for caspase-independent PCD. Since UCH-L1 clearly contributes to the non-apoptotic death of podocytes, interference with the necroptotic properties of HtrA2/Omi and UCH-L1 may prove beneficial for the treatment of patients, e.g. in kidney failure.
Expression changes of ionic channels in early phase of cultured rat atrial myocytes induced by rapid pacing
Authors: Ji Qiang , Liu Hua , Mei Yunqing , Wang Xisheng , Feng Jing , Ding Wenjun 
Published: September 2013

Abstract

Background
Recent studies have demonstrated that atrial electrical remodeling was an important contributing factor for the occurrence, persistence and maintenance of atrial fibrillation. The expression changes of ionic channels, especially L-type calcium channel and potassium channel Kv4.3, were the important molecular mechanism of atrial electrical remodeling. This study aimed to observe the expression changes of ionic channels in a rapid paced cell model with primary cultured atrial myocytes.

Methods
The primary rat atrial myocytes were cultured, characteristics of the cultured myocytes were observed with light microscope and the cell phenotype was harvested by immunocytochemical stain to detect α-actin. The cellular model of rapid pacing was established with primary cultured atrial myocytes. The expressions of L-type calcium channel α1c and potassium channel Kv4.3 in cultured atrial myocytes were detected by immunocytochemistry, reverse transcription polymerase chain reaction and Western blot after rapid pacing.

Results
The primary rat atrial myocytes were isolated and cultured successfully, and used for following experiment by identification of activity and purity. Cellular model of rapid electrical field pacing was established successfully. There is no significant difference in cell activity after pacing compared to that before pacing by 3-[4, 5-dimethylthiazol-2-y1]-2, 5-diphenytetrazolium bromide assay, and cell degeneration can be observed by transmission electron microscope. The mRNA expression of L-type calcium channel α1c started to reduce after 6 h of rapid pacing and continued to decline as pacing continued. Protein expression changes were paralleled with decreased mRNA expression of the L-type calcium channel α1c. The mRNA expressions of potassium channel Kv4.3 were not altered within the first 6 h, but after 12 h, mRNA expressions were reduced. Longer pacing periods did not further decrease mRNA expression of potassium channel Kv4.3. Protein expression changes were paralleled with decreased mRNA expression of potassium channel Kv4.3.

Conclusions
Rapid paced cultured atrial myocyte model was established utilized primary cultured atrial myocytes and this model can be used for studying the early electrical remodeling in atrial fibrillation. Expressions of L-type calcium channel α1c and potassium channel Kv4.3 were both reduced at different levels in early phase of rapid pacing atrial myocytes. It implicates the occurrence of ionic channel remodeling of atrial myocytes.
Clinical significance of cytogenetic aberrations in bone marrow of patients with diffuse large B-cell lymphoma: prognostic significance and relevance to histologic involvement
Authors: Kim Seon Young , Kim Hyo Jung , Kang Hye Jin , Kim Jin Seok , Eom Hyeon Seok , Kim Tae Min , Yoon Sung-Soo , Suh Cheolwon , Lee Dong Soon ,   Korean Society of Hematology Lymphoma Working Party
Published: October 2013

Abstract

Background
Although knowledge of the genetics of diffuse large B-cell lymphoma (DLBCL) has been increasing, little is known about the characteristics and prognostic significance of cytogenetic abnormalities and the clinical utility of cytogenetic studies performed on bone marrow (BM) specimens. To investigate the significance of isolated cytogenetic aberrations in the absence of histologic BM involvement, we assessed the implication of cytogenetic staging and prognostic stratification by a retrospective multicenter analysis of newly diagnosed DLBCL patients.

Methods
We analyzed cytogenetic and clinical data from 1585 DLBCL patients whose BM aspirates had been subjected to conventional karyotyping for staging. If available, interphase fluorescence in situ hybridization (FISH) data were also collected from patients.

Results
Histologic BM involvement were found in 259/1585 (16.3%) patients and chromosomal abnormalities were detected in 192 (12.1%) patients (54 patients with single abnormalities and 138 patients with 2 or more abnormalities). Isolated cytogenetic aberrations (2 or more abnormalities) without histologic involvement were found in 21 patients (1.3%). Two or more cytogenetic abnormalities were associated with inferior overall survival (OS) compared with a normal karyotype or single abnormality in both patients with histologic BM involvement (5-year OS, 22.0% vs. 52.7%; P < 0.001) and those without BM involvement (31.8% vs. 66.5%; P < 0.001). This result demonstrated that BM cytogenetic results have a significant prognostic impact that is independent of BM histology. The following abnormalities were most frequently observed: rearrangements involving 14q32, 19q13, 19p13, 1p, 3q27, and 8q24; del(6q); dup(1q); and trisomy 18. In univariate analysis, several specific abnormalities including abnormalities at 16q22-q24, 6p21-p25, 12q22-q24, and -17 were associated with poor prognosis. Multivariate analyses performed for patients who had either chromosomal abnormalities or histologic BM involvement, revealed IPI high risk, ≥ 2 cytogenetic abnormalities, and several specific chromosomal abnormalities, including abnormalities at 19p13, 12q22-q24, 8q24, and 19q13 were significantly associated with a worse prognosis.

Conclusions
We suggest that isolated cytogenetic aberrations can be regarded as BM involvement and cytogenetic evaluation of BM improves staging accuracy along with prognostic information for DLBCL patients.
Long-term survival after intensive care unit discharge in Thailand: a retrospective study
Authors: Luangasanatip Nantasit , Hongsuwan Maliwan , Lubell Yoel , Limmathurotsakul Direk , Teparrukkul Prapit , Chaowarat Sirirat , Day NicholasPJ , Graves Nicholas , Cooper Ben S 
Published: October 2013

Abstract
Introduction
Economic evaluations of interventions in the hospital setting often rely on the estimated long-term impact on patient survival. Estimates of mortality rates and long-term outcomes among patients discharged alive from the intensive care unit (ICU) are lacking from lower- and middle-income countries. This study aimed to assess the long-term survival and life expectancy (LE) amongst post-ICU patients in Thailand, a middle-income country.

Methods
In this retrospective cohort study, data from a regional tertiary hospital in northeast Thailand and the regional death registry were linked and used to assess patient survival time after ICU discharge. Adult ICU patients aged at least 15 years who had been discharged alive from an ICU between 1 January 2004 and 31 December 2005 were included in the study, and the death registry was used to determine deaths occurring in this cohort up to 31st December 2010. These data were used in conjunction with standard mortality life tables to estimate annual mortality and life expectancy.

Results
This analysis included 10,321 ICU patients. During ICU admission, 3,251 patients (31.5%) died. Of 7,070 patients discharged alive, 2,527 (35.7%) were known to have died within the five-year follow-up period, a mortality rate 2.5 times higher than that in the Thai general population (age and sex matched). The mean LE was estimated as 18.3 years compared with 25.2 years in the general population.

Conclusions
Post-ICU patients experienced much higher rates of mortality than members of the general population over the five-year follow-up period, particularly in the first year after discharge. Further work assessing Health Related Quality of Life (HRQOL) in both post-ICU patients and in the general population in developing countries is needed.
Epidermal growth factor receptor inhibitor therapy for recurrent respiratory papillomatosis
Authors: Moldan Matthew M. , Bostrom Bruce C , Tibesar Robert J , Lander Timothy A. , Sidman James D. 
Published: October 2013

The epidermal growth factor pathway has been implicated in various tumors, including human papillomavirus (HPV) lesions such as recurrent respiratory papillomatosis (RRP). Due to the presence of epidermal growth factor receptors in RRP, epidermal growth factor receptor (EGFR) inhibitors have been utilized as adjuvant therapy. This case series examines the response to EGFR inhibitors in RRP. Four patients with life-threatening RRP were treated with EGFR inhibitors. Operative frequency and anatomical Derkay scores were calculated prior to, and following EGFR inhibitor treatment via retrospective chart review. The anatomical Derkay score decreased for all four patients after initiation of EGFR inhibitor therapy. In one patient, the operative frequency increased after switching to an intravenous inhibitor after loss of control with an oral inhibitor. In the other patients there was a greater than 20% decrease in operative frequency in one and a more than doubling in the time between procedures in two. This study suggests that EGFR inhibitors are a potential adjuvant therapy in RRP and deserve further study in a larger number of patients.