bluuebunny/crossref_metadata_2025_split huggingface dataset:
The uplift of the Qinghai–Tibet Plateau and glacial oscillations triggered the diversification of Tetraogallus (Galliformes, Phasianidae)
Authors: Ding Li , Liao Jicheng , Liu Naifa 
Published: January 2020

AbstractThe Qinghai–Tibet Plateau (QTP) plays an important role in avian diversification. To reveal the relationship between the QTP uplift and avian diversification since the Late Cenozoic, here, we analyzed the phylogenetic relationship and biogeographical pattern of the genus Tetraogallus (Galliformes, Phasianidae) and the probable factors of speciation in the period of the QTP uplift inferred from concatenated data of four nuclear and five mitochondrial genes using the method of the Bayesian inference. Phylogenetic analysis indicated that T. himalayensis had a close relationship with T. altaicus and conflicted with the previous taxonomy of dark‐bellied and white‐bellied groups. The molecular clock showed that the speciation of Tetraogallus was profoundly affected by the uplift of the QTP and glacial oscillations. Biogeographic analysis suggested that the extant snowcocks originated from the QTP, and the QTP uplift and glacial oscillations triggered the diversification of Tetraogallus ancestor. Specifically, the uplift of the mountain provided a prerequisite for the colonization of snowcocks Tetraogallus as a result of the collision between the Indian and the Arab plates and the Eurasian plate, in which ecological isolation (the glacial and interglacial periods alternate) and geographical barrier had accelerated the Tetraogallus diversification process. Interestingly, we discovered hybrids between T. tibetanus and T. himalayensis for the first time and suggested that T. tibetanus and T. himalayensis hybridized after a second contact during the glacial period. Here, we proposed that the hybrid offspring was the ancestor of the T. altaicus. In conclusion, the uplift of QTP and glacial oscillations triggered the snowcocks colonization, and then, isolation and introgression hybridization promoted diversification.
Organization of Squamata (Reptilia) assemblages in Mediterranean archipelagos
Authors: Escoriza Daniel 
Published: January 2020

AbstractMediterranean islands have complex reptile assemblages, but little is known about the factors that determine their organization. In this study, the structure of assemblages of Squamata was evaluated based on their species richness and two measures of phylogenetic diversity (variability and clustering). I evaluated the composition of the assemblages comparing distinct biogeographic subregions within the Mediterranean: Adriatic, Aegean, Balearic, Corsica–Sardinia, Crete, Gulf of Gabés, Ionian Sea, Ligurian Sea, Malta, Sicily, and Tyrrhenian Sea. The effect of island environments and geographical isolation on the diversity metrics was assessed using generalized linear models. The analyses indicated that species richness was mostly influenced by island area and geographical isolation. Assemblages on smaller islands were poorer in species and phylogenetically dispersed, possibly as an effect of interspecific competition. The species composition of the assemblages was determined by similar environmental drivers within the biogeographic subregions, including island area, island elevation, geographical isolation, and aridity. In several subregions, significant patterns of phylogenetic attraction were found in species co‐occurrences, caused by the limits imposed by the island size on large predatory species.
Late diagnosis of Barth syndrome in a 39‐year‐old patient with non‐compaction cardiomyopathy and neutropenia
Authors: Seitz Andreas , Hinck Annely , Bekeredjian Raffi , Sechtem Udo 
Published: January 2020

AbstractBarth syndrome is a rare X‐linked recessive disorder characterized by a broad spectrum of clinical features including cardiac and skeletal myopathy, neutropenia, exercise intolerance, and growth delay. Most affected patients are diagnosed during childhood, and mortality is highest in the first years of life. As a consequence, Barth syndrome is often considered a paediatric disease. Here, we report a case where the diagnosis was established in a 39‐year‐old patient with left ventricular non‐compaction and neutropenia. The clinical course of the patient presented here was relatively benign. This suggests that the prevalence of Barth syndrome in adults may be underestimated. Barth syndrome should be considered in the differential diagnosis of male patients with cardiomyopathy and neutropenia.
CT‐IGFBP‐4 as a novel prognostic biomarker in acute heart failure
Authors: Konev Alexey A. , Kharitonov Alexey V. , Rozov Fedor N. , Altshuler Evgeny P. , Serebryanaya Daria V. , Lassus Johan , Harjola Veli‐Pekka , Katrukha Alexey G. , Postnikov Alexander B. 
Published: January 2020

AbstractAimsInsulin‐like growth factor binding protein‐4 (IGFBP‐4) fragments have been shown to predict the risk of major adverse cardiovascular events, including segment‐elevation myocardial infarction, in patients with acute coronary syndrome. We evaluated the prognostic value of the carboxy‐terminal fragment of IGFBP‐4 (CT‐IGFBP‐4) for all‐cause mortality in emergency room patients with acute heart failure (AHF).Methods and resultsCT‐IGFBP‐4, N‐terminal pro brain natriuretic peptide (NT‐proBNP), and C‐reactive protein (CRP) were measured at admission from the lithium‐heparin plasma of 156 patients with AHF. All‐cause mortality was recorded for 1 year. Receiver operator characteristic (ROC) curves, Kaplan–Meier, and Cox proportional hazard ratio analyses were performed to evaluate the prognostic value of the various clinical variables, CT‐IGFBP‐4, NT‐proBNP, CRP, and their combinations. During 1 year of follow‐up, 52 (33.3%) patients died. CT‐IGFBP‐4 only weakly correlated with NT‐proBNP (Pearson correlation coefficient r = 0.16, P = 0.044) and did not correlate with CRP (r = 0.08, P = 0.35), emphasizing the different nature of these biomarkers. The receiver operator characteristic area under the curve (ROC AUC) of CT‐IGFBP‐4 for the prediction of all‐cause mortality (0.727) was significantly higher than that of NT‐proBNP (0.680, P = 0.045) and CRP (0.669, P = 0.016). The combination of CT‐IGFBP‐4, NT‐proBNP, and CRP predicted mortality significantly better (ROC AUC = 0.788) than any of the biomarkers alone (P < 0.01 for all). The addition of CT‐IGFBP‐4 to a clinical prediction model that included age, gender, systolic blood pressure, creatinine, and sodium levels, as well as the history of previous heart failure, coronary artery disease, and hypertension significantly improved the mortality risk prediction (ROC AUC 0.774 vs. 0.699, P = 0.025). Cox hazard analysis indicated that elevated CT‐IGFBP‐4 was independently associated with 1 year mortality (hazard ratio 3.26, P = 0.0008) after adjustment for age, gender, history of previous heart failure, coronary artery disease, hypertension, chronic kidney failure, history of diabetes, heart rate, haemoglobin, plasma sodium, NT‐proBNP, CRP, cystatin C, and elevated cardiac troponin I or T. Patients with increased levels of either two or three of the biomarkers CT‐IGFBP‐4, NT‐proBNP, and CRP had significantly higher mortality risk (adjusted hazard ratio 10.04, P < 0.0001) than patients with increased levels of one or none of the biomarkers.ConclusionsCT‐IGFBP‐4 was independently associated with all‐cause mortality in patients with AHF. Compared with single biomarkers, the combination of CT‐IGFBP‐4, NT‐proBNP, and CRP improved the prediction of all‐cause mortality in patients with AHF.
Highly degraded RNA can still provide molecular information: An in vitro approach
Authors: Fattorini Paolo , Bonin Serena , Marrubini Giorgio , Bertoglio Barbara , Grignani Pierangela , Recchia Elisa , Pitacco Paola , Zupanič Pajnič Irena , Sorçaburu‐Ciglieri Solange , Previderè Carlo 
Published: January 2020

AbstractThe long‐term survival of RNA in postmortem tissues is a tricky topic. Many aged/forensic specimens show, in fact, high rates of null/inconclusive PCR‐based results, while reliable outcomes were sometimes achieved from archaeological samples. On the other hand, several data show that the RNA is a molecule that survives even to several physical–chemical stresses. In the present study, a simple protocol, which was already developed for the prolonged hydrolysis of DNA, was applied to a RNA sample extracted from blood. This protocol is based on the heat‐mediated (70°C) hydrolysis for up to 36 h using ultrapure water and di‐ethyl‐pyro‐carbonate‐water as hydrolysis medium. Measurable levels of depurination were not found even if microfluidic devices showed a progressive pattern of degradation. The reverse transcription/quantitative PCR analysis of two (60 bp long) housekeeping targets (glyceraldehyde‐3‐phosphate dehydrogenase and porphobilinogen deaminase) showed that the percentage of amplifiable target (%AT) decreased in relation to the duration of the damaging treatment (r2 > 0.973). The comparison of the %AT in the degraded RNA and in the DNA samples that underwent the same damaging treatment showed that the %AT is always higher in RNA, reaching up to three orders of magnitude. Lastly, even the end‐point PCR of blood‐specific markers gave reliable results, which is in agreement with the body fluid origin of the sample. In conclusion, all the PCR‐based results show that RNA maintains the ability to be retro‐transcribed in short cDNA fragments even after 36 h of incubation at 70°C in mildly acidic buffers. It is therefore likely that the long‐term survival of RNA samples depends mainly on the protection against RNAase attacks rather than on environmental factors (such as humidity and acidity) that are instead of great importance for the stability of DNA. As a final remark, our results suggest that the RNA analysis can be successfully performed even when DNA profiling failed.
A novel approach enables imaged capillary isoelectric focusing analysis of PEGylated proteins
Authors: Zhang Xin , Chemmalil Letha , Ding Julia , Li Zhengjian 
Published: January 2020

AbstractPEGylation has been used as a strategy to enhance pharmacokinetic properties of therapeutic proteins by pharmaceutical industry. Imaged CIEF (iCIEF) is the current industry standard technology for pI determination and charge variant quantification of proteins and antibodies. However, the charge variants of PEGylated proteins merge into one broad peak during iCIEF, most likely due to masking of proteins by the surrounding PEG chain as well as the increased hydrodynamic volume due to PEGylation. Here, we report our novel matrix formula with a combination of glycine and taurine that significantly improved the separation of charge variants in PEGylated proteins. As a result, it is no longer necessary to conduct IEF of proteins prior to PEGylation, which does not reflect the changes caused by PEGylation and purification processes. The novel matrix (glycine and taurine) enables iCIEF analysis of PEGylated proteins in their real conjugated states.
Predicting the radial heat transfer in the wellbore of cryogenic nitrogen fracturing: Insights into stimulating underground reservoir
Authors: Song Weiqiang , Shi Xian , Wang Chunguang , Xu Jianchun , Chen Shaojie , Chen Zhongwei 
Published: January 2020

AbstractCryogenic nitrogen fracturing is an attractive method for stimulating underground reservoir, since it could favorably induce complex fracture due to the huge temperature difference with lower injection pressure and with the replacement of current water‐based fracturing fluid. However, the concern about whether cryogenic nitrogen would be overheated remains unrevealed in the engineering environment with large wellbore length. In addition, reservoir stimulation results are also related with the pressure state at bottom hole. Therefore, in this study, a mathematical model was proposed to predict the radial heat transfer and its influence on vertical pressure transmission in the wellbore with cryogenic nitrogen as fracturing fluid. The model fully couples the heat transfer, hydraulics, and the compressibility of nitrogen, and then, the calculation results were presented and analyzed through a case study. According to the results, the temperature of nitrogen increases too fast under conventional engineering conditions, and it changes into gaseous state at the depth lower than 100 m. Finally, the temperature difference between nitrogen and formation rock becomes too minimal to induce thermal stress at bottom hole. Due to the fast temperature increase, the density of nitrogen decreases too much, and the vertical pressure increasing rate by liquid nitrogen (1.66 MPa/km) is merely 18.2% that in carbon dioxide fracturing (9.13 MPa/km). The results indicate that utilization of special casing with much larger thermal resistance is an indispensable approach to realize the feasibility and advantages of cryogenic nitrogen fracturing.
Diagnostic yield of NanoString nCounter FusionPlex profiling in soft tissue tumors
Authors: Song Wangzhao , Platteel Inge , Suurmeijer Albert J. H. , van Kempen Léon C. 
Published: January 2020

AbstractDiagnostic histopathology of soft tissue tumors can be troublesome as many entities are quite rare and have overlapping morphologic features. Many soft tissue tumors harbor tumor‐defining gene translocations, which may provide an important ancillary tool for tumor diagnosis. The NanoString nCounter platform enables multiplex detection of pre‐defined gene fusion transcripts in formalin‐fixed and paraffin‐embedded tissue. A cohort of 104 soft tissue tumors representing 20 different histological types was analyzed for the expression of 174 unique gene fusion transcripts. A tumor‐defining gene fusion transcript was detected in 60 cases (58%). Sensitivity and specificity of the NanoString assay calculated against the result of an alternative molecular method were 85% and 100%, respectively. Highest diagnostic coverage was obtained for Ewing sarcoma, synovial sarcoma, myxoid liposarcoma, alveolar rhabdomyosarcoma, and desmoplastic small round cell tumor. For these tumor types, the NanoString assay is a rapid, cost‐effective, sensitive, and specific ancillary screening tool for molecular diagnosis. For other sarcomas, additional molecular testing may be required when a translocation transcript is not identified with the current 174 gene fusion panel.
A process‐based approach to attribution of historical streamflow decline in a data‐scarce and human‐dominated watershed
Authors: Penny Gopal , Srinivasan Veena , Apoorva R. , Jeremiah Kirubaharan , Peschel Joshua , Young Sierra , Thompson Sally 
Published: January 2020

AbstractHuman activities have resulted in rapid hydrological change around the world, in many cases producing shifts in the dominant hydrological processes, confounding predictions, and complicating effective management and planning. Identifying and characterizing such changes in hydrological processes is therefore a globally relevant problem, one that is particularly challenging in sparsely monitored environments. We develop a novel, process‐based approach for attribution of hydrological change in such scenarios and apply the approach to the TG Halli watershed outside Bangalore, India, where streamflow has declined considerably over the last 50 years. The approach consists of (a) employing a range of field instrumentation and experiments to identify contemporary streamflow generation mechanisms, (b) using these observations to constrain our understanding and generate hypotheses pertaining to historical changes, and (c) evaluating these hypotheses with a range of evidence including proxies for historical hydrological processes. The body of evidence in the TG Halli watershed indicates the historical presence and subsequent loss of a shallow groundwater table that previously discharged to the stream, meaning that groundwater depletion is the most likely driver of streamflow decline. These findings present a viable path towards improved predictions of future water resources and sustainable water management within the watershed. Our process‐based approach to attribution has the potential to improve understanding of human‐driven hydrological change in regions with poor monitoring of hydrological systems.
Testing a theoretical resistance law for overland flow on a stony hillslope
Authors: Nicosia Alessio , Di Stefano Costanza , Pampalone Vincenzo , Palmeri Vincenzo , Ferro Vito , Nearing Mark A. 
Published: January 2020

AbstractOverland flow, sediments, and nutrients transported in runoff are important processes involved in soil erosion and water pollution. Modelling transport of sediments and chemicals requires accurate estimates of hydraulic resistance, which is one of the key variables characterizing runoff water depth and velocity. In this paper, a new theoretical power–velocity profile, originally deduced neglecting the impact effect of rainfall, was initially modified for taking into account the effect of rainfall intensity. Then a theoretical flow resistance law was obtained by integration of the new flow velocity distribution. This flow resistance law was tested using field measurements by Nearing for the condition of overland flow under simulated rainfall. Measurements of the Darcy–Weisbach friction factor, corresponding to flow Reynolds number ranging from 48 to 194, were obtained for simulated rainfall with two different rainfall intensity values (59 and 178 mm hr−1). The database, including measurements of flow velocity, water depth, cross‐sectional area, wetted perimeter, and bed slope, allowed for calibration of the relationship between the velocity profile parameter Γ, the slope steepness s, and the flow Froude number F, taking also into account the influence of rainfall intensity i. Results yielded the following conclusions: (a) The proposed theoretical flow resistance equation accurately estimated the Darcy–Weisbach friction factor for overland flow under simulated rainfall, (b) the flow resistance increased with rainfall intensity for laminar overland flow, and (c) the mean flow velocity was quasi‐independent of the slope gradient.
Nonclinical safety assessment of repeated administration and biodistribution of ChAd3‐EBO‐Z Ebola candidate vaccine
Authors: Planty Camille , Chevalier Guillaume , Duclos Marie‐Ève , Chalmey Clémentine , Thirion‐Delalande Catherine , Sobry Cécile , Steff Ann‐Muriel , Destexhe Eric 
Published: January 2020

AbstractChAd3‐EBO‐Z is an investigational adenovirus‐based vaccine for the prevention of Ebola virus disease. Two nonclinical studies were performed to evaluate the biodistribution, local tolerance and potential local and systemic toxic effects of this vaccine. In the biodistribution study, rats received a single intramuscular injection of either ChAd3‐EBO‐Z or saline. Enlargement of the draining lymph nodes, starting on day 2, was noticed in ChAd3‐EBO‐Z‐treated rats, indicating that an immune response had taken place. Viral DNA was mainly found at the injection sites and in the draining lymph nodes, from where it progressively disappeared during the observation period, while it was found only transiently and occasionally in other organs. In the repeated‐dose toxicity study, either ChAd3‐EBO‐Z or saline was administered intramuscularly to rabbits on two occasions with a 2‐week interval. General health status, rectal temperature, local tolerance, ophthalmology, hematology, coagulation and blood chemistry parameters were monitored. Macroscopic and microscopic evaluations were performed. Treatment‐related changes included a transient increase in neutrophil count, C‐reactive protein and fibrinogen levels, and a transient decrease in platelet count. As expected, microscopic observations 3 days after the second injection were related to the elicited inflammatory reaction, and these inflammatory responses had almost completely disappeared 29 days after the second immunization. In conclusion, the vaccine was locally and systemically well‐tolerated and the viral vector was partially or totally cleared from the organs where it disseminated, supporting the clinical development of the vaccine.
Biomarkers in WNT1 and PLS3 Osteoporosis: Altered Concentrations of DKK1 and FGF23
Authors: Mäkitie Riikka E , Kämpe Anders , Costantini Alice , Alm Jessica J , Magnusson Per , Mäkitie Outi 
Published: January 2020

ABSTRACT
Recent advancements in genetic research have uncovered new forms of monogenic osteoporosis, expanding our understanding of the molecular pathways regulating bone health. Despite active research, knowledge on the pathomechanisms, disease-specific biomarkers, and optimal treatment in these disorders is still limited. Mutations in WNT1, encoding a WNT/β-catenin pathway ligand WNT1, and PLS3, encoding X chromosomally inherited plastin 3 (PLS3), both result in early-onset osteoporosis with prevalent fractures and disrupted bone metabolism. However, despite marked skeletal pathology, conventional bone markers are usually normal in both diseases. Our study aimed to identify novel bone markers in PLS3 and WNT1 osteoporosis that could offer diagnostic potential and shed light on the mechanisms behind these skeletal pathologies. We measured several parameters of bone metabolism, including serum dickkopf-1 (DKK1), sclerostin, and intact and C-terminal fibroblast growth factor 23 (FGF23) concentrations in 17 WNT1 and 14 PLS3 mutation-positive subjects. Findings were compared with 34 healthy mutation-negative subjects from the same families. Results confirmed normal concentrations of conventional metabolic bone markers in both groups. DKK1 concentrations were significantly elevated in PLS3 mutation-positive subjects compared with WNT1 mutation-positive subjects (p &lt; .001) or the mutation-negative subjects (p = .002). Similar differences were not seen in WNT1 subjects. Sclerostin concentrations did not differ between any groups. Both intact and C-terminal FGF23 were significantly elevated in WNT1 mutation-positive subjects (p = .039 and p = .027, respectively) and normal in PLS3 subjects. Our results indicate a link between PLS3 and DKK1 and WNT1 and FGF23 in bone metabolism. The normal sclerostin and DKK1 levels in patients with impaired WNT signaling suggest another parallel regulatory mechanism. These findings provide novel information on the molecular networks in bone. Extended studies are needed to investigate whether these biomarkers offer diagnostic value or potential as treatment targets in osteoporosis. © 2020 American Society for Bone and Mineral Research.
Neuroprotective efficacy of nano‐CoQ against propionic acid toxicity in rats: Role of BDNF and CREB protein expressions
Authors: Alhusaini Ahlam , Hasan Iman H. , Alrumayyan Bashayer , Alesikri Marwa , Alanazi Khansa , Almasoud Rawan , Almarshad Sarah 
Published: January 2020

AbstractPropionic acid (PRA) is used as a food preservative. This study was aimed to investigate the neuroprotective effect of acetyl‐l‐carnitine (ALC) and nano‐Coenzyme Q (N‐CoQ) on brain intoxication induced by PRA in rats. Rats were divided into five groups: group I: control; group II: received PRA; group III: received ALC; group IV: received N‐CoQ; and group V: received ALC and N‐CoQ for 5 days. The antioxidants in question markedly ameliorated serum interleukin‐1β and tumor necrosis factor‐α, and brain NO, lipid peroxide, glutathione, and superoxide dismutase levels as well as protein expression of brain‐derived neurotrophic factor (BDNF) and P‐cyclic‐AMP response element‐binding protein (CREB) that were altered by a toxic dose of PRA, as well as histopathological alterations, including improvement of the cerebellum architecture. Interestingly, the combination therapy of ALC and N‐CoQ achieved the most neuroprotective effect compared with monotherapies. The current study established that N‐CoQ is considered as a useful tool to prevent brain injury induced by PRA. BDNF and CREB proteins are involved in both PRA neurotoxicity and treatment.