bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microsomal PGE2 synthase‐1 regulates melanoma cell survival and associates with melanoma disease progression
Authors: Kim Sun‐Hee , Hashimoto Yuuri , Cho Sung‐Nam , Roszik Jason , Milton Denái R. , Dal Fulya , Kim Sangwon F. , Menter David G. , Yang Peiying , Ekmekcioglu Suhendan , Grimm Elizabeth A. 
Published: January 2016

SummaryCOX‐2 and its product PGE2 enhance carcinogenesis and tumor progression, which has been previously reported in melanoma. As most COX inhibitors cause much toxicity, the downstream microsomal PGE2 synthase‐1 (mPGES1) is a consideration for targeting. Human melanoma TMAs were employed for testing mPGES1 protein staining intensity and percentage levels, and both increased with clinical stage; employing a different Stage III TMA, mPGES1 intensity (not percentage) associated with reduced patient survival. Our results further show that iNOS was also highly expressed in melanoma tissues with high mPGES1 levels, and iNOS‐mediated NO promoted mPGES1 expression and PGE2 production. An mPGES1‐specific inhibitor (CAY10526) as well as siRNA attenuated cell survival and increased apoptosis. CAY10526 significantly suppressed tumor growth and increased apoptosis in melanoma xenografts. Our findings support the value of a prognostic and predictive role for mPGES1, and suggest targeting this molecule in the PGE2 pathway as another avenue toward improving melanoma therapy.
The Intricacies of Shell Shock: A Chronological History of The Lancet's Publications by Dr. Charles S. Myers and His Contemporaries
Authors: Fueshko Tara M. 
Published: January 2016

Originally defined as a “derangement of the nervous system deriving primarily from explosion at close range,” shell shock became a medical diagnosis for war trauma during the Great War. The term originated due to the subjection of exploding shells in dug out trenches, but came to encompass a variety of war trauma due to the horrors of modern warfare. Previous wars acknowledged war trauma by the common theme of weak heartedness leading to the derogatory outlook on the soldier who could not bear up under the pressures of war. However, the wars prior to 1900 did not use the tactics seen in The Great War and emphasis on the psychological ramifications of trauma was limited. Countries like Great Britain were therefore unprepared for the war trauma that occurred between 1914 and 1918. Faced with inadequate information and old practices, the field of Psychiatry grew in prominence as the state and its society looked for answers for the syndrome. Doctors such as Charles S. Myers published their findings in The Lancet, a medical journal aimed at publishing original research as well as reviews, correspondence, news, and case reports. This paper focuses on the publications of Dr. Myers, his contemporaries, the evolution of shell shock as a psychosomatic illness, and its progressive shift in British medical practices that paved the way for further analysis and treatment on war trauma as well as mental illness going forward.
The temporal ‘structure’ and function of the insect photoperiodic clock: a tribute to Colin S. Pittendrigh
Authors: Saunders David S. 
Published: January 2016

AbstractIn 1936, Erwin Bünning suggested that photoperiodic time measurement was a function of the circadian system. Colin Pittendrigh became an ardent supporter of Bünning's hypothesis, drawing parallels between photoperiodism and his own group's investigations of adult eclosion rhythmicity in the fruit fly Drosophila pseudoobscura. They developed several more modern versions of Bünning's general hypothesis based on the entrainment of circadian oscillations to the light cycle, including ‘external coincidence’, which is a derivation of Bünning's original model, and ‘internal coincidence’, which relied upon seasonal changes in the mutual phase relationship of oscillators within a multi‐oscillator circadian system. This review considers the experimental evidence for the central role of the circadian system in photoperiodic timing and, in some species, for both external and internal coincidence. Pittendrigh, however, pursued the idea of internal coincidence further with his analysis of the pacemaker–slave organization of eclosion rhythmicity in D. pseudoobscura and proposed a similar theoretical model for photoperiodism comprising a group of slave oscillators driven by a light‐sensitive pacemaker. In this model, the phase relationships of the slaves to the pacemaker were affected by (i) the relative periods of the pacemaker and slave(s); (ii) the strength(s) of the coupling between the two; and (iii) the dampening coefficients of the various slaves. Manipulation of these variables showed that the slaves adopted different internal phase relationships (both to each other and to the pacemaker) under the influence of changes in daily photophase, the period of the Zeitgeber and phase shifts of the entraining light cycle.
Evaluation of immune responses induced by rhoptry protein 5 and rhoptry protein 7 DNA vaccines against Toxoplasma gondii
Authors: Wang L. , Lu G. , Zhou A. , Han Y. , Guo J. , Zhou H. , Cong H. , He S. 
Published: January 2016

SummaryInfection with the protozoan parasite Toxoplasma gondii is widespread, and the organism can cause congenital infections in humans. The horizontal transmission of Toxoplasma is even more common than congenital. An effective vaccine strategy brings the prospect of improving Toxoplasma disease control. Rhoptry protein 5 (ROP5) and ROP7 are potential stimulators of humoral and cellular immune responses. In this study, we constructed a multi‐antigenic DNA vaccine expressing ROP5 and ROP7 of T. gondii and compared the protective efficacy to single‐gene vaccines and control groups. BALB/c mice were immunized intramuscularly three times. The levels of IgG antibodies and cytokines in mice immunized with the multi‐antigenic DNA vaccine (pROP5/ROP7) were significantly higher than those in the control mice. Mice vaccinated with pROP5/ROP7 showed a longer survival time (16 days) than single‐gene‐immunized mice (11 and 12 days, respectively) or control mice (8 days) after a challenge with 1 × 104 tachyzoites of RH strain of T. gondii. Furthermore, after intragastric infection with 20 cysts of PRU strain of T. gondii, the number of brain cysts in mice immunized with pROP5/ROP7 was only 25% of the number in control mice. Our results showed that a DNA vaccine encoding ROP5 and ROP7 significantly enhanced protection against T. gondii challenge.
Complex coastal change in response to autogenic basin infilling: An example from a sub‐tropical Holocene strandplain
Authors: Hein Christopher J. , FitzGerald Duncan M. , de Souza Luis H. P. , Georgiou Ioannis Y. , Buynevich Ilya V. , Klein Antonio H. da F. , de Menezes João Thadeu , Cleary William J. , Scolaro Thelma L. 
Published: January 2016

AbstractThick bay‐fill sequences that often culminate in strandplain development serve as important sedimentary archives of land–ocean interaction, although distinguishing between internal and external forcings is an ongoing challenge. This study employs sediment cores, ground‐penetrating radar surveys, radiocarbon dates, palaeogeographic reconstructions and hydrodynamic modelling to explore the role of autogenic processes – notably a reduction in wave energy in response to coastal embayment infilling – in coastal evolution and shoreline morphodynamics. Following a regional 2 to 4 m highstand at ca 5·8 ka, the 75 km2 Tijucas Strandplain in southern Brazil built from fluvial sediments deposited into a semi‐enclosed bay. Holocene regressive deposits are underlain by fluvial sands and a Pleistocene transgressive–regressive sequence, and backed by a highstand barrier‐island. The strandplain is immediately underlain by 5 to 16 m of seaward‐thickening, fluvially derived, Holocene‐age, basin‐fill mud. Several trends are observed from the landward (oldest) to the seaward (youngest) sections of the strandplain: (i) the upper shoreface and foreshore become finer and thinner and shift from sand‐dominated to mud‐dominated; (ii) beachface slopes decrease from >11° to ca 7°; and (iii) progradation rates increase from 0·4 to 1·8 m yr−1. Hydrodynamic modelling demonstrates a correlation between progressive shoaling of Tijucas Bay driven by sea‐level fall and sediment infilling and a decrease in onshore wave‐energy transport from 18 to 4 kW m−1. The combination of allogenic (sediment supply, falling relative sea‐level and geology) and autogenic (decrease in wave energy due to bay shoaling) processes drove the development of a regressive system with characteristics that are rare, if not unique, in the Holocene and rock records. These findings demonstrate the complexities in architecture styles of highstand and regressive systems tracts. Furthermore, this article highlights the diverse internal and external processes and feedbacks responsible for the development of these intricate marginal marine sedimentary systems.
SOT1, a pentatricopeptide repeat protein with a small MutS‐related domain, is required for correct processing of plastid 23S–4.5S rRNA precursors in Arabidopsis thaliana
Authors: Wu Wenjuan , Liu Sheng , Ruwe Hannes , Zhang Delin , Melonek Joanna , Zhu Yajuan , Hu Xupeng , Gusewski Sandra , Yin Ping , Small Ian D. , Howell Katharine A. , Huang Jirong 
Published: January 2016

SummaryRibosomal RNA processing is essential for plastid ribosome biogenesis, but is still poorly understood in higher plants. Here, we show that SUPPRESSOR OF THYLAKOID FORMATION1 (SOT1), a plastid‐localized pentatricopeptide repeat (PPR) protein with a small MutS‐related domain, is required for maturation of the 23S–4.5S rRNA dicistron. Loss of SOT1 function leads to slower chloroplast development, suppression of leaf variegation, and abnormal 23S and 4.5S processing. Predictions based on the PPR motif sequences identified the 5′ end of the 23S–4.5S rRNA dicistronic precursor as a putative SOT1 binding site. This was confirmed by electrophoretic mobility shift assay, and by loss of the abundant small RNA ‘footprint’ associated with this site in sot1 mutants. We found that more than half of the 23S–4.5S rRNA dicistrons in sot1 mutants contain eroded and/or unprocessed 5′ and 3′ ends, and that the endonucleolytic cleavage product normally released from the 5′ end of the precursor is absent in a sot1 null mutant. We postulate that SOT1 binding protects the 5′ extremity of the 23S–4.5S rRNA dicistron from exonucleolytic attack, and favours formation of the RNA structure that allows endonucleolytic processing of its 5′ and 3′ ends.
Hematopoietic peripheral circulating blood stem cells as an independent marker of good transfusion management in patients with β‐thalassemia: results from a preliminary study
Authors: Napolitano Mariasanta , Gerardi Calogera , Di Lucia Anna , Accardo Pietro Andrea , Rizzuto Luigi , Ferraro Maria , Siragusa Sergio , Buscemi Filippo 
Published: January 2016

BACKGROUNDBeyond hemoglobin (Hb) levels and performance status, further surrogate markers of appropriate transfusion management should improve the quality of thalassemia care. We investigated the levels of peripheral circulating CD34+ stem cells as an independent marker of appropriate hematopoietic balance in patients with thalassemia.STUDY DESIGN AND METHODSPeripheral circulating CD34+ stem cells, colony‐forming unitgranulocyte, erythrocyte, macrophage, magakaryocyte (CF‐GEMM), colony‐forming unitgranulocyte/macrophage (CFU‐GM), and erythroidburst‐forming units (BFU‐E) were assayed, according to standard procedures. Patients with thalassemia major (TM) and thalassemia intermedia (TI) were tested and compared to healthy controls. Demographic and clinical data were recorded.RESULTSOverall, 56 patients with TM (median age, 35 years; range, 13‐52 years) and 13 with TI (median age, 44 years; range, 27‐67 years) were evaluated. Annual red blood cell (RBC) transfusion requirements ranged from 10 to 65 units in all patients except four nontransfused cases. A significant increase in peripheral circulating stem cells was observed in patients, in comparison with healthy controls. Nontransfused patients showed the mean highest levels of stem cells (CD34, 32.5 ± 14.8/μL; BFU‐E, 41.3 ± 22.8/mL; CFU‐GM, 19.6 ± 5.6/mL; CFU‐GEMM, 9.0 ± 6.1/mL). CD34+ cell count was 6.9 ± 4.5/μL in TM (p = 0.014) and 11.8 ± 14.8/μL (p = 0.051) in TI. Furthermore, only in patients with TI was a significant increase in CFU‐GEMM (3.0 ± 4.8 vs. 0.75 ± 2.05/mL, p = 0.0001) observed. At multivariate analysis, peripheral circulating CD34+ stem cells did not correlate with age, sex, smoking habit, number of RBCs units transfused, Hb levels, iron chelation therapy, history of splenectomy, and hypothyroidism.CONCLUSIONCirculating peripheral CD34 + stem cells are increased in β‐thalassemia, in particular in nontransfused patients, compared to healthy controls.
Effect of intravenous iron on outcomes of acute kidney injury
Authors: Clark Barbara A. , Osadchuk Liliana , John Jones , Culver Thuyanh , Marcus Richard 
Published: January 2016

BACKGROUNDLittle is known about benefit versus risk in treating iron deficiency anemia with intravenous (IV) iron in patients with acute kidney injury (AKI). Concerns about adverse outcomes may dissuade use and could contribute to greater use of red blood cell (RBC) transfusion.STUDY DESIGN AND METHODSWe performed a retrospective case‐control study of patients with AKI who received IV iron (cases) compared to those with AKI without IV iron (controls).RESULTSWe identified 67 cases and 67 controls matched for age, stage of chronic kidney disease, and severity of anemia (hemoglobin [Hb], 7.7 ± 0.1 mg/dL vs. 7.5 ± 0.1 mg/dL; p = 0.47). Cases tended to be sicker with longer length of stay (27 + 4 days vs. 15 + 1.3 days; p = 0.003) and more intensive care unit days (13 + 2 days vs. 5 + 1 days; p = 0.003), more often with diagnosis of sepsis and greater number of antibiotics used (2.7 ± 0.3 vs. 1.8 ± 0.2; p = 0.02). Sepsis and AKI preceded use of IV iron. Despite greater illness severity, there was no difference in dialysis (38.8% vs. 34.3%; p = 0.59), mortality (24% vs. 21%; p = 0.679), or severity and/or recovery of AKI. Discharge Hb was similar (9.0 ± 0.1 mg/dL vs. 9.1 ± 0.1 mg/dL; p = 0.47). IV iron was used later in the stay and hence the cases also had more RBC transfusions.CONCLUSIONSWe were unable to find any adverse consequences of use of IV iron when used to treat anemia in patients with AKI in regard to recovery of AKI or mortality even in patients with a diagnosis of sepsis. Consideration of preemptive use of IV iron in AKI with severe anemia is warranted to determine if this would reduce RBC transfusion.
Impact of using different blood donor subpopulations and models on the estimation of transfusion transmission residual risk of human immunodeficiency virus, hepatitis B virus, and hepatitis C virus in Zimbabwe
Authors: Mapako Tonderai , Janssen Mart P. , Mvere David A. , Emmanuel Jean C. , Rusakaniko Simbarashe , Postma Maarten J. , van Hulst Marinus 
Published: January 2016

BACKGROUNDVarious models for estimating the residual risk (RR) of transmission of infections by blood transfusion have been published mainly based on data from high‐income countries. However, to obtain the data required for such an assessment remains challenging for most developing settings. The National Blood Service Zimbabwe (NBSZ) adapted a published incidence‐window period (IWP) model, which has less demanding data requirements. In this study we assess the impact of various definitions of blood donor subpopulations and models on RR estimates. We compared the outcomes of two published models and an adapted NBSZ model.STUDY DESIGN AND METHODSThe Schreiber IWP model (Model 1), an amended version (Model 2), and an adapted NBSZ model (Model 3) were applied. Variably the three models include prevalence, incidence, preseroconversion intervals, mean lifetime risk, and person‐years at risk. Annual mean RR estimates and 95% confidence intervals for each of the three models for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) were determined using NBSZ blood donor data from 2002 through 2011.RESULTSThe annual mean RR estimates for Models 1 through 3 were 1 in 6542, 5805, and 6418, respectively for HIV; 1 in 1978, 2027, and 1628 for HBV; and 1 in 9588, 15,126, and 7750, for HCV.CONCLUSIONSThe adapted NBSZ model provided comparable results to the published methods and these highlight the high occurrence of HBV in Zimbabwe. The adapted NBSZ model could be used as an alternative to estimate RRs when in settings where two repeat donations are not available.
Effect of storage conditions on subpopulations of peripheral blood T lymphocytes isolated from naïve cattle and cattle infected with foot‐and‐mouth disease virus
Authors: Eschbaumer Michael , Stenfeldt Carolina , Pacheco Juan M. , Rekant Steven I. , Arzt Jonathan 
Published: January 2016

BackgroundImmunophenotyping of blood lymphocytes by flow cytometry is important in infectious disease research. In animal experiments and other longitudinal studies, the processing, prompt staining, and analysis of fresh samples is a logistical challenge and daily assay variation can confound data interpretation.ObjectiveThis study examined the feasibility of cryopreservation and deferred analysis of bovine peripheral blood T lymphocytes from normal or infected animals.MethodsPeripheral blood mononuclear cells were collected from 4 naïve Holstein steers and 4 steers infected with foot‐and‐mouth‐disease virus serotype Asia1. Identical aliquots were labeled and analyzed immediately, labeled for deferred analysis, or stored at −70°C or over liquid nitrogen for up to 3 weeks before labeling.ResultsFreezing of unlabeled cells induced statistically significant changes in phenotypic recognition. In infected animals, the γδ T‐cell population increased by 28% and CD8+ αβT cells by 32%, while total CD3+ cells decreased by 16%, and CD4+ αβT cells decreased by 12%. Subsequent storage of frozen cells for the duration of the study, however, had no significant effect. There was less than 20% relative change in subpopulation sizes, and storage at −70°C or over liquid nitrogen was equivalent.ConclusionsDepending on the objectives and practical limitations of a study, deferred labeling of peripheral blood lymphocytes can be a viable option. Although frozen storage of lymphocytes can introduce some artifactual distortion of relative cell populations, frozen cells can be maintained in storage until all samples in a longitudinal study can be analyzed in batch under standardized conditions and without introducing further bias.
The diagnostic value of two commercially available human cTnI assays in goat kids with myocarditis
Authors: Karapinar Tolga , Eroksuz Yesari , Hayirli Armagan , Beytut Enver , Kaynar Ozgur , Baydar Ersoy , Sozdutmaz Ibrahim , Isidan Hakan 
Published: January 2016

BackgroundCardiac troponin I (cTnI) is a peripheral blood marker for myocardial damage. Because of the unavailability of goat‐specific cTnI assays human cTnI assays may be validated for detection of myocarditis in goat kids.ObjectivesThe purpose of the study was to evaluate 2 commercially available human cTnI assays in goat kids with myocardial damage, and to determine the cTnI expression in cardiac muscle.Materials and MethodsPlasma cTnI concentrations were measured in healthy goat kids (n = 7) and goat kids with myocardial damage (n = 8) using the Beckman Coulter Access Accu TnI and the Biomérieux Vidas Ultra. The results were correlated with gross necropsy and histopathologic findings, and cTnI immunhistochemistry in cardiac tissue.ResultsMacro‐ and microscopic findings confirmed myocardial damage in the myocarditis group. Mean plasma cTnI concentration was significantly higher in the myocarditis group than in the healthy control group (104.82 vs 0.02 ng/mL). The overall mean plasma cTnI concentration measured by Biomérieux Vidas Ultra (61.75 ng/mL, 95% CI: 19.55–103.95) was comparable to the mean measured by Beckman Coulter Access Accu TnI (50.08 ng/mL, 95% CI: 24.11–76.06), and cTnI concentrations measured by these assays were highly correlated (r = .977) with a −6.2% bias. Both assays were precise and accurate.ConclusionThe human‐specific Beckman Coulter Access Accu TnI and the Biomérieux Vidas Ultra can be used for diagnostic confirmation of myocardial damage in caprine medicine.
Interaction between left ventricular twist mechanics and arterial haemodynamics during localised, non‐metabolic hyperaemia with and without blood flow restriction
Authors: van Mil Anke C. C. M. , Pearson James , Drane Aimee L. , Cockcroft John R. , McDonnell Barry J. , Stöhr Eric J. 
Published: January 2016

New Findings

What is the central question of this study?
Left ventricular (LV) twist is reduced when afterload is increased, but the meaning of this specific heart muscle response and its impact on cardiac output are not well understood.

What is the main finding and its importance?
This study shows that LV twist responds even when arterial haemodynamics are altered only locally, and without apparent change in metabolic (i.e. heat‐induced) demand. The concurrent decline in cardiac output and LV twist during partial arterial occlusion despite the increased peripheral demand caused by heat stress suggests that LV twist may be involved in the protective sensing of heart muscle stress that can override the provision of the required cardiac output.

Whether left ventricular (LV) twist and untwisting rate (LV twist mechanics) respond to localised, peripheral, non‐metabolic changes in arterial haemodynamics within an individual's normal afterload range is presently unknown. Furthermore, previous studies indicate that LV twist mechanics may override the provision of cardiac output, but this hypothesis has not been examined purposefully. Therefore, we acutely altered local peripheral arterial haemodynamics in 11 healthy humans (women/men n = 3/8; age 26 ± 5 years) by bilateral arm heating (BAH). Ultrasonography was used to examine arterial haemodynamics, LV twist mechanics and the twist‐to‐shortening ratio (TSR). To determine the arterial function‐dependent contribution of LV twist mechanics to cardiac output, partial blood flow restriction to the arms was applied during BAH (BAHBFR). Bilateral arm heating increased arm skin temperatures [change (Δ) +6.4 ± 0.9°C, P < 0.0001] but not core temperature (Δ −0.0 ± 0.1°C, P > 0.05), concomitant to increases in brachial artery blood flow (Δ 212 ± 77 ml, P < 0.0001), cardiac output (Δ 495 ± 487 l min−1, P < 0.05), LV twist (Δ 3.0 ± 3.5 deg, P < 0.05) and TSR (Δ 3.3 ± 1.3, P < 0.05) but maintained carotid artery blood flow (Δ 18 ± 147 ml, P > 0.05). Subsequently, BAHBFR reduced all parameters to preheating levels, except for TSR and heart rate, which remained at BAH levels. In conclusion, LV twist mechanics responded to local peripheral arterial haemodynamics within the normal afterload range, in part independent of TSR and heart rate. The findings suggest that LV twist mechanics may be more closely associated with intrinsic sensing of excessive pressure stress rather than being associated with the delivery of adequate cardiac output.