bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acid sphingomyelinase – a regulator of canonical transient receptor potential channel 6 (TRPC6) activity
Authors: Zeitler Stefanie , Ye Lian , Andreyeva Aksana , Schumacher Fabian , Monti Juliana , Nürnberg Bernd , Nowak Gabriel , Kleuser Burkhard , Reichel Martin , Fejtová Anna , Kornhuber Johannes , Rhein Cosima , Friedland Kristina 
Published: July 2019

AbstractRecent investigations propose the acid sphingomyelinase (ASM)/ceramide system as a novel target for antidepressant action. ASM catalyzes the breakdown of the abundant membrane lipid sphingomyelin to the lipid messenger ceramide. This ASM‐induced lipid modification induces a local shift in membrane properties, which influences receptor clustering and downstream signaling. Canonical transient receptor potential channels 6 (TRPC6) are non‐selective cation channels located in the cell membrane that play an important role in dendritic growth, synaptic plasticity and cognition in the brain. They can be activated by hyperforin, an ingredient of the herbal remedy St. John’s wort for treatment of depression disorders. Because of their role in the context of major depression, we investigated the crosstalk between the ASM/ceramide system and TRPC6 ion channels in a pheochromocytoma cell line 12 neuronal cell model (PC12 rat pheochromocytoma cell line). Ca2+ imaging experiments indicated that hyperforin‐induced Ca2+ influx through TRPC6 channels is modulated by ASM activity. While antidepressants, known as functional inhibitors of ASM activity, reduced TRPC6‐mediated Ca2+ influx, extracellular application of bacterial sphingomyelinase rebalanced TRPC6 activity in a concentration‐related way. This effect was confirmed in whole‐cell patch clamp electrophysiology recordings. Lipidomic analyses revealed a decrease in very long chain ceramide/sphingomyelin molar ratio after ASM inhibition, which was connected with changes in the abundance of TRPC6 channels in flotillin‐1–positive lipid rafts as visualized by western blotting. Our data provide evidence that the ASM/ceramide system regulates TRPC6 channels likely by controlling their recruitment to specific lipid subdomains and thereby fine‐tuning their physical properties.
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Oral pyogenic granulomas show MAPK/ERK signaling pathway activation, which occurs independently of BRAF, KRAS, HRAS, NRAS, GNA11, and GNA14 mutations
Authors: Pereira Thaís dos Santos Fontes , de Amorim Larissa Stefhanne Damasceno , Pereira Núbia Braga , Vitório Jéssica Gardone , Duarte‐Andrade Filipe Fideles , Guimarães Letícia Martins , Diniz Marina Gonçalves , Gomes Carolina Cavaliéri , Gomez Ricardo Santiago 
Published: July 2019

AbstractBackgroundPyogenic granuloma (PG) is a benign nodular lesion with a prominent vascular component which may affect different sites. Recently, BRAF, KRAS, HRAS, NRAS, GNA11, and GNA14 mutations were reported on PGs of the skin. The present study assessed the role of the MAPK/ERK pathway in oral PG pathogenesis.MethodsMutations in hotspot regions of genes involved in the MAPK/ERK pathway activation were investigated by Sanger sequencing. The expression of phospho‐ERK1/2 was evaluated by immunohistochemistry.ResultsOral PGs did not show mutations in the sequenced regions of the genes BRAF, KRAS, HRAS, NRAS, GNA11, or GNA14. Our results also showed activation of the MAPK/ERK pathway demonstrated by phospho‐ERK1/2 immunohistochemical positivity.ConclusionsAlthough oral PG shows MAPK/ERK pathway activation, the driver molecular event remains to be elucidated.
Atmospheric entry heating of micrometeorites at Earth and Mars: Implications for the survival of organics
Authors: Wilson Aaron P. , Genge Matthew J. , Krzesińska Agata M. , Tomkins Andrew G. 
Published: July 2019

AbstractThe atmospheric entry heating of micrometeorites (MMs) can significantly alter their pre‐existing mineralogy, texture, and organic material. The degree of heating depends predominantly on the gravity and atmospheric density of the planet on which they fall. For particles falling on Earth, the alteration can be significant, leading to the destruction of much of the pre‐entry organics; however, the weaker gravity and thinner atmosphere of Mars enhance the survival of MMs and increase the fraction of particles that preserve organic material. This paper investigates the entry heating of MMs on the Earth and Mars in order to examine the MM population on each planet and give insights into the survival of extraterrestrial organic material. The results show that particles reaching the surface of Mars experience a lower peak temperature compared to Earth and, therefore, experience less evaporative mass loss. Of the particles which reach the surface, 68.2% remain unmelted on Mars compared to only 22.8% on Earth. Due to evaporative mass loss, unmelted particles that reach the surface of Earth are restricted to sizes <70 μm whereas particles >475 μm survive unmelted on Mars. Approximately 10% of particles experience temperatures below ~800 K, that is, the sublimation temperature of refractory organics found in MMs. On Earth, this fraction is significantly lower with less than 1% expected to remain below this temperature. Lower peak temperatures coupled with the larger sizes of particles surviving without significant heating on Mars suggest a much higher fraction of organic material surviving to the Martian surface.
Extracellular acidosis triggers a senescence‐like phenotype in human melanoma cells
Authors: Böhme Ines , Bosserhoff Anja 
Published: July 2019

AbstractAcidosis of the tumor microenvironment is a characteristic of solid tumors such as malignant melanoma. Main causes of the extracellular acidification are metabolic alterations in cancer cells. While numerous studies showed that acidosis promotes tumor invasiveness, metastasis, and neoangiogenesis resulting in malignant progression, contrary data reported that acidosis induces cell apoptosis, inhibits cell proliferation, and mediates cell autophagy. Here, we show that low pH (pH 6.7) induces senescent/quiescent phenotype in melanoma cells after long‐time treatment defined by induction of SA‐ß‐galactosidase, upregulation of p21, G1/G0 cell cycle arrest, and reduction of proliferation. Moreover, we revealed that extracellular acidosis triggers the inhibition of eIF2α and subsequently the activation of ATF4 expression, a key component of the integrated stress response (ISR), indicating an acid‐mediated translation reprogramming. Interestingly, we also demonstrated that acidosis represses microphthalmia‐associated transcription factor (MITF) and activates the expression of the receptor tyrosine kinase AXL. This MITFlow/AXLhigh phenotype is correlated with drug resistance and therapeutic outcome in melanoma. Our results suggest that acidosis is an important microenvironmental factor triggering phenotypic plasticity and promoting tumor progression.
Reference values for selected ophthalmic diagnostic tests in two species of microchiroptera bats (Artibeus lituratus and Anoura caudifer)
Authors: Somma André Tavares , Coimbra Christiane M. , Lange Rogério R. , Moore Bret A. , Montiani‐Ferreira Fabiano 
Published: July 2019

AbstractObjectiveTo establish reference values for ophthalmic tests in two bat species.BatsFourteen bats including seven great fruit‐eating bats (Artibeus lituratus) and seven tailed tailless bats (Anoura caudifer).ProceduresNormal values for following ophthalmic tests were investigated as follows: (a) aqueous tear production using the standardized endodontic paper point tear test (EPPTT), (b) rebound tonometry, and (c) horizontal palpebral fissure length.ResultsAqueous tear production was 2.53 ± 1.65 mm/min for A lituratus and 1.89 ± 0.62 for A caudifer. Intraocular pressure measured in the upright position was 11.0 ± 3.28 mm Hg for A lituratus and 7.28 ± 2.70 for A caudifer. Horizontal palpebral fissure length was 5.04 ± 0.45 mm for A lituratus and 3.92 ± 0.51 for A caudifer.ConclusionsThe data obtained in the present study may serve as a reference for ophthalmic parameters and help practitioners in the diagnosis and management of eye diseases in bats, as well for future investigations about microchiroptera bats.
Tear production, intraocular pressure, and central corneal thickness in white‐tailed deer (Odocoileus virginianus)
Authors: Villar Tatiane , Pascoli Ana L. , Klein Aislinn , Chacaltana Flor C. , Capistrano Erotides , Shipley Cliff F. , Martins Bianca C. 
Published: July 2019

AbstractObjectiveTo evaluate the tear production, intraocular pressure, and central corneal thickness in healthy white‐tailed deer (Odocoileus virginianus) and assess for seasonal variability.Animals studiedNineteen healthy fawns (3‐10 days old) and 8 healthy adult white‐tailed deer (164‐280 days old) were studied.ProceduresAll fawns were manually restrained for the study, while adult animals were immobilized with an intramuscular injection of combined xylazine (2.2 mg/kg), tiletamine (1 mg/kg), and zolazepam (1 mg/kg). Tear production (STT‐1) was evaluated in both eyes of all fawns. Intraocular pressure (applanation and rebound tonometry) and central corneal thickness (ultrasound pachymetry) were determined in both eyes of all fawns and adult deer.ResultsMean ± SD tear production in fawns was 12.32 ± 4.46 mm/min. Mean ± SD IOP values in the fawns were 16.21 ± 4.97 mm Hg (TonoPen®) and 14.05 ± 5.03 mm Hg (TonoVet®). In adult deer, mean ± SD IOP values were 15.57 ± 2.88 mm Hg with TonoPen®and 12.87 ± 2.57 with TonoVet®, and TonoPen®significantly overestimated the IOP, compared to TonoVet®(P < 0.005). The IOP was not significantly different between young and adult animals (P = 0.22). A significant difference (P < 0.005) in CCT values was observed between fawns (528.42 ± 27.65 μm) and adult deer (747.55 ± 41.60 μm).ConclusionsThis study reports normal values of tear production in healthy fawns, and intraocular pressure and central corneal thickness in healthy young and adult white‐tailed deer.
Integrated stratigraphy at the Bartonian–Priabonian transition: Correlation between shallow benthic and calcareous plankton zones (Varignano section, northern Italy)
Authors: Luciani Valeria , Fornaciari Eliana , Papazzoni Cesare A. , Dallanave Edoardo , Giusberti Luca , Stefani Cristina , Amante Enrico 
Published: July 2019

AbstractThe Varignano section (Trento province, northern Italy) provides an exceptional opportunity for a direct correlation between shallow benthic (SB) zones and standard calcareous plankton zones at the Bartonian–Priabonian transition (middle–late Eocene). This transition has attracted great attention by biostratigraphers in the last decades in searching for a boundary stratotype section. The Alano di Piave section (NE Italy) is the leading candidate for the base Priabonian Global Stratotype Section and Point (GSSP). However, at Alano, larger foraminifera-bearing resedimented levels occur exclusively well below the critical interval. Conversely, the Varignano section, located ∼80 km west of the Alano section, preserves several coarse bioclastic levels rich in larger foraminifera throughout the section. These levels are intercalated with basinal marlstones, crystal tuff layers, and an organic-rich interval. The Varignano section spans planktic foraminiferal Zones E10 and E11 to lower E14, calcareous nannofossil Zones MNP16Bc to MNP18 and Chrons 18n to 17n.2n. The main calcareous plankton events recently proposed as primary base-Priabonian correlation tools, i.e., the last occurrence of the genus Morozovelloides and the Base common (= acme beginning) of Cribrocentrum erbae occur, respectively, within C17n.3n and C17n.2n. We correlate prominent crystal tuff layers exposed at Varignano with those outcropping at Alano, including the Tiziano bed, whose base has also been proposed as the GSSP level. The Varignano section spans the upper SB17 and the lower SB18 Zones, with the zonal boundary marked by the first occurrence of the genus Pellatispira. This event occurs in the lower part of Zones E13 and MNP17A within C18n, well below all the potential criteria to identify the GSSP that also includes Chron C17n.1n base. We point out that the usage of shallow-water biostratigraphers in placing the base of the Priabonian at the base of Zone SB19 is inconsistent with the proposed plankton events.
Is female genital mutilation/cutting associated with adverse mental health consequences? A systematic review of the evidence
Authors: Abdalla Salma M , Galea Sandro 
Published: July 2019

IntroductionThe adverse physical consequences of female genital mutilation/cutting (FGM/C) have been thoroughly investigated and documented. Yet, we know little about the adverse mental health consequences of the practice. To fill this research gap, we systematically reviewed studies that assessed any adverse mental health consequences related to FGM/C.MethodsWe searched four databases from inception to 21 December 2018. We then reviewed all titles and abstracts for relevant studies. We used the National Institutes of Health quality assessment tool to appraise the quality of each study and the Newcastle-Ottawa Scale to rate the risk of bias within studies.ResultsWe included 16 studies in this review; only six studies examined the association between FGM/C and adverse mental health outcomes as the sole research question. Among the included studies, 10 were conducted at the participants’ country of origin. The sample size of the populations studied ranged from 3 to 4800 participants. Only one study received a rating of ‘good’ methodological quality.Fourteen of the 16 studies reported an association between FGM/C and at least adverse mental health outcome. These included eight studies that reported a higher burden of adverse mental health outcomes among women who underwent FGM compared with women who did not undergo FGM/C. Four studies reported a correlation between the severity of FGM/C and the severity of adverse mental health outcomes.ConclusionThis systematic review documents an association between FGM/C and adverse mental health outcomes. Importantly, our review demonstrates the need for more rigorous research on the topic.
Responding to epidemics in large-scale humanitarian crises: a case study of the cholera response in Yemen, 2016–2018
Authors: Spiegel Paul , Ratnayake Ruwan , Hellman Nora , Ververs Mija , Ngwa Moise , Wise Paul H , Lantagne Daniele 
Published: July 2019

BackgroundLarge epidemics frequently emerge in conflict-affected states. We examined the cholera response during the humanitarian crisis in Yemen to inform control strategies.MethodsWe conducted interviews with practitioners and advisors on preparedness; surveillance; laboratory; case management; malnutrition; water, sanitation and hygiene (WASH); vaccination; coordination and insecurity. We undertook a literature review of global and Yemen-specific cholera guidance, examined surveillance data from the first and second waves (28 September 2016–12 March 2018) and reviewed reports on airstrikes on water systems and health facilities (April 2015–December 2017). We used the Global Task Force on Cholera Control’s framework to examine intervention strategies and thematic analysis to understand decision making.ResultsYemen is water scarce, and repeated airstrikes damaged water systems, risking widespread infection. Since a cholera preparedness and response plan was absent, on detection, the humanitarian cluster system rapidly developed response plans. The initial plans did not prioritise key actions including community-directed WASH to reduce transmission, epidemiological analysis and laboratory monitoring. Coordination was not harmonised across the crisis-focused clusters and epidemic-focused incident management system. The health strategy was crisis focused and was centralised on functional health facilities, underemphasising less accessible areas. As vaccination was not incorporated into preparedness, consensus on its use remained slow. At the second wave peak, key actions including data management, community-directed WASH and oral rehydration and vaccination were scaled-up.ConclusionDespite endemicity and conflict, Yemen was not prepared for the epidemic. To contain outbreaks, conflict-affected states, humanitarian agencies, and donors must emphasise preparedness planning and community-directed responses.
Why are people increasingly attending the emergency department? A study of the French healthcare system
Authors: Colineaux Helene , Pelissier Fanny , Pourcel Laure , Lang Thierry , Kelly-Irving Michelle , Azema Olivier , Charpentier Sandrine , Lamy Sebastien 
Published: July 2019

ObjectiveIt is often asserted that the crowding phenomenon in emergency departments (ED) can be explained by an increase in visits considered as non-urgent. The aim of our study was to quantify the increase in ED visit rates and to determine whether this increase was explained by non-severe visit types.MethodsThis observational study covers all ED visits between 2002 and 2015 by adult inhabitants of the Midi-Pyrénées region in France. Their characteristics were collected from the emergency visit summaries. We modelled the visit rates per year using linear regression models, and an increase was considered significant when the 95% CIs did not include zero. The severity of the patients’ condition during ED visit was determined through the ‘Clinical Classification of Emergency’ score. Non-severe visits were those where the patient was stable, and the physician deemed no intervention necessary. Intermediate-severity visits concerned patients who were stable but requiring diagnostic or therapeutic procedures.ResultsThe 37 studied EDs managed >7 million visits between 2002 and 2015. There was an average increase of +4.83 (95% CI 4.33 to 5.32) visits per 1000 inhabitants each year. The increase in non-severe visit types was +0.88 (95% CI 0.42 to 1.34) per 1000 inhabitants, while the increase in intermediate-severity visit types was +3.26 (95% CI 2.62 to 3.91) per 1000 inhabitants. This increase affected all age groups and all sexes.DiscussionIt appears that the increase in ED use is not based on an increase in non-severe visit types, with a greater impact of intermediate-severity visit types requiring diagnostic or therapeutic procedures in ED.
A look into the cosmological consequences of a dark energy model with higher derivatives of H in the framework of Chameleon Brans–Dicke cosmology
Authors: Pasqua Antonio , Chattopadhyay Surajit , Beesham Aroonkumar 
Published: July 2019

In this paper, we study some relevant cosmological features of a Dark Energy (DE) model with Granda–Oliveros cut-off, which is just a specific case of Nojiri–Odintsov holographic DE [S. Nojiri and S. D. Odintsov, Gen. Relativ. Gravit. 38 (2006) 1285] unifying phantom inflation with late-time acceleration, in the framework of Chameleon Brans–Dicke (BD) cosmology. Choosing a particular ansatz for some of the quantities involved, we derive the expressions of some important cosmological quantities, like the Equation of State (EoS) parameter of DE [Formula: see text], the effective EoS parameter [Formula: see text], the pressure of DE [Formula: see text] and the deceleration parameter [Formula: see text]. Moreover, we study the behavior of statefinder parameters [Formula: see text] and [Formula: see text], of the cosmographic parameters [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text] and of the squared speed of the sound [Formula: see text] for both case corresponding to noninteracting and interacting Dark sectors. We also plot the quantities we have derived and we calculate their values for [Formula: see text] (i.e. for the beginning of the universe history), for [Formula: see text] (i.e. for far future) and for the present time, indicated with [Formula: see text]. The EoS parameters have been tested against various observational values available in the literature.
RATIONALIZATION OF SURGICAL TREATMENT FOR HEMORRHAGIC MOYAMOYA DISEASE: FROM LABORATORY BENCH RESEARCH, BIOMECHANICS TO META-ANALYSIS
Authors: JIANG ZHI-QUN , CHEN YAN , ZENG CHUN-HUI , FENG JIU-GENG , WAN YI-LV , WEI MIN-JUN 
Published: July 2019

Background and purpose: Surgery is recommended as the treatment of choice for hemorrhagic Moyamoya disease (MMD). The rationale of surgery and the choice of procedure are poorly understood. The aim of this paper is to present latest evidence, from cellular, biomechanical and population data, surgical treatment options and their effect on the outcome of hemorrhagic MMD. Methods: We systematically reviewed the latest evidence from cellular, biomechanical and populational studies including our own meta-analysis for rationalization of management of MMD. We searched major databases from inception to latest articles available till October 2018. All major breakthroughs including basic research to randomized controlled trials (RCTs) and human case–control studies related to hemorrhagic MMD were included. Our meta-analysis was performed in accordance to the standard Cochrane. Result: Evidence at cellular, biomechanical and RCT levels was presented. For our meta-analysis, we included eight studies, totaling at 632 patients. Our results rationalized the use of surgical methods in support of surgical management of MMD. We showed that surgery in MMD resulted in a significant lower risk of future stroke ([Formula: see text], 95% [Formula: see text]–0.38). Among different surgical methods, the indirect bypass group had a lower risk for sedentary stroke risk reduction compared with the direct bypass group (RR[Formula: see text]=[Formula: see text]3.36, 95% CI[Formula: see text]=[Formula: see text]1.53–7.36). No significant differences were observed in perioperative complications between the two methods. Conclusion: Surgery remains a mainstay for the management of MMD. We concluded that current evidence in biomechanical and our own meta-analysis is in support of surgery being an effective management of hemorrhagic MMD. We deduced insights into research for early detection, characterization and follow up of patients with MMD.
A Near-Infrared Phosphorescent Nanoprobe Enables Quantitative, Longitudinal Imaging of Tumor Hypoxia Dynamics during Radiotherapy
Authors: Zheng Xianchuang , Cui Liyang , Chen Min , Soto Luis A. , Graves Edward E. , Rao Jianghong 
Published: July 2019

Abstract

Hypoxia plays a key role in tumor resistance to radiotherapy. It is important to study hypoxia dynamics during radiotherapy to improve treatment planning and prognosis. Here, we describe a luminescent nanoprobe, composed of a fluorescent semiconducting polymer and palladium complex, for quantitative longitudinal imaging of tumor hypoxia dynamics during radiotherapy. The nanoprobe was designed to provide high sensitivity and reversible response for the subtle change in hypoxia over a narrow range (0–30 mmHg O2), which spans the oxygen range where tumors have limited radiosensitivity. Following intravenous administration, the nanoprobe efficiently accumulated in and distributed across the tumor, including the hypoxic region. The ratio between emissions at 700 and 800 nm provided quantitative mapping of hypoxia across the entire tumor. The nanoprobe was used to image tumor hypoxia dynamics over 7 days during fractionated radiotherapy and revealed that high fractional dose (10 Gy) was more effective in improving tumor reoxygenation than low dose (2 Gy), and the effect tended to persist longer in smaller or more radiosensitive tumors. Our results also indicated the importance of the reoxygenation efficiency of the first fraction in the prediction of the radiation treatment outcome. In summary, this work has established a new nanoprobe for highly sensitive, quantitative, and longitudinal imaging of tumor hypoxia dynamics following radiotherapy, and demonstrated its value for assessing the efficacy of radiotherapy and radiation treatment planning.

Significance:
This study presents a novel nanoagent for the visualization and quantification of tumor hypoxia.