bluuebunny/crossref_metadata_2025 huggingface dataset:
The T‐box transcription factor brachyury behaves as a tumor suppressor in gliomas
Authors: Pinto Filipe , Costa Ângela M , Santos Gisele C , Matsushita Marcus M , Costa Sandra , Silva Viviane AO , Miranda‐Gonçalves Vera , Lopes Celeste M , Clara Carlos A , Becker Aline P , Neder Luciano , Hajj Glaucia NM , da Cunha Isabela W , Jones Chris , Andrade Raquel P , Reis Rui M
Published: March 2020

The oncogene brachyury (TBXT) is a T‐box transcription factor that is overexpressed in multiple solid tumors and is associated with tumor aggressiveness and poor patient prognosis. Gliomas comprise the most common and aggressive group of brain tumors, and at the present time the functional and clinical impact of brachyury expression has not been investigated previously in these neoplasms. Brachyury expression (mRNA and protein) was assessed in normal brain (n = 67), glioma tissues (n = 716) and cell lines (n = 42), and further in silico studies were undertaken using genomic databases totaling 3115 samples. Our glioma samples were analyzed for copy number (n = 372), promoter methylation status (n = 170), and mutation status (n = 1569 tissues and n = 52 cell lines) of the brachyury gene. The prognostic impact of brachyury expression was studied in 1524 glioma patient tumors. The functional impact of brachyury on glioma proliferation, viability, and cell death was evaluated both in vitro and in vivo.

Brachyury was expressed in the normal brain, and significantly downregulated in glioma tissues. Loss of brachyury was associated with tumor aggressiveness and poor survival in glioma patients. Downregulation of brachyury was not associated with gene deletion, promoter methylation, or inactivating point mutations. Brachyury re‐expression in glioma cells was found to decrease glioma tumorigenesis by induction of autophagy. These data strongly suggest that brachyury behaves as a tumor suppressor gene in gliomas by modulating autophagy. It is important to note that brachyury constitutes an independent positive biomarker of patient prognosis. Our findings indicate that the role of brachyury in tumorigenesis may be tissue‐dependent and demands additional investigation to guide rational interventions. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Microwave‐assisted in situ polymerization of polycaprolactone/boron nitride composites with enhanced thermal conductivity and mechanical properties
Authors: Tian Hongli , Wu Fangjuan , Chen Peng , Peng Xiangfang , Fang Hui
Published: March 2020

Polycaprolactone/boron nitride (PCL/BN) composites were prepared by microwave‐assisted ring‐opening polymerization of ε‐caprolactone (ε‐CL). In order to improve the dispersibility and interfacial interaction between BN fillers and PCL matrix, hydroxyl functional BN (mBN) was first prepared to be used as a macroinitiator for ε‐CL. Then BN grafted PCL (BN‐g‐PCL) copolymers were obtained via the in situ method, which acted as in situ compatibilizers in the PCL/BN composites. Various techniques were applied to characterize the mBN and PCL/BN composites. The Fourier transform infrared spectroscopy results confirm the structure of the BN‐g‐PCL copolymer. Field emission SEM graphs exhibit that, for the PCL/mBN composites, the mBN presents a homogeneous dispersion in the matrix and interfacial adhesion between the PCL and mBN is improved. These are beneficial for enhancing the thermal conductivity of the PCL/mBN composites. Notably, the PCL/mBN composite with 5 wt% mBN loading achieves the highest thermal conductivity of 0.55 W m−1 K−1, which is 2.75 times higher than that of pure PCL, 0.20 W m−1 K−1. This indicates that the excellent dispersion and interfacial adhesion could lead to the construction of continuous thermal conductive paths at a low BN loading and reduce the heat loss caused by phonon scattering in the interface. Furthermore, mBN could help to improve the mechanical properties of the composite. On adding 5 wt% mBN, the tensile strength and tensile modulus of the composite are 1.58 and 2.05 times higher, respectively, than those of PCL. © 2020 Society of Chemical Industry
Associations between self‐reported physical activity, quality of life, and emotional well‐being in men with prostate cancer on active surveillance
Authors: Papadopoulos Efthymios , Alibhai Shabbir M. H. , Doré Isabelle , Matthew Andrew G. , Tomlinson George A. , Nesbitt Michael , Finelli Antonio , Trachtenberg John , Santa Mina Daniel
Published: March 2020

Objective

The relationship between physical activity (PA) and quality of life (QOL) relative to active treatment for prostate cancer (PCa) has been well‐studied; however, little is known about this relationship during active surveillance (AS). Moreover, whether PA is associated with better emotional well‐being (EWB) in men with low‐risk PCa requires further investigation. Accordingly, we examined the association between self‐reported PA and the average change in QOL and EWB over time during AS.

Methods

A total of 630 men on AS were included in this retrospective, longitudinal study from AS initiation until AS discontinuation. Generalized estimated equations were used to determine the association between self‐reported PA (independent variable) and QOL and EWB (dependent variables) over time, adjusting for participants' age.

Results

QOL was higher over time in active ((95%CI) = 1.14 (0.11, 2.16), P = .029) and highly active participants ((95%CI) = 1.62 (0.58, 2.67), P = .002) compared to their inactive counterparts. Highly active participants had 55% greater odds of experiencing high EWB relative to inactive participants (OR (95%CI) = 1.55 (1.11, 2.16), P = .010). In men with low EWB at baseline (median = 3 months after diagnosis), the highest levels of PA (>1000 metabolic equivalent‐minutes per week) were associated with high EWB over time (OR (95%CI) = 2.17 (1.06, 4.46), P = .034).

Conclusions

These data further support the importance of PA as a supportive care strategy for men on AS. Our findings suggest that engaging in higher volumes of PA post‐diagnosis may be beneficial particularly for men exhibiting low emotional well‐being early on during AS.
Substance use behaviors in adolescent and young adult cancer patients: Associations with mental and physical health
Authors: Asvat Yasmin , King Andrea C. , Smith Lia J. , Lin Xiaolei , Hedeker Donald , Henderson Tara O.
Published: March 2020

Objective

Cancer diagnosis in adolescents and young adults (AYAs) coincides with the developmental initiation of substance use and emergence of affective disturbance. We examined substance use behaviors and risk‐stratified associations with mental and physical health, as well as objective indicators of tobacco and cannabis use and concordance with self‐report and medical records.

Methods

AYAs were 15 to 39 years at cancer diagnosis and ≥18 years and ≥6 months postdiagnosis at study enrollment. Risk‐stratified groups included nonsmoker/nondrinker, nonsmoker/drinker, smoker/drinker. Assessments included demographics, past year tobacco, alcohol, and cannabis use, depression, anxiety, sleep, and physical activity. Urine analysis provided biochemical verification of tobacco and cannabis use.

Results

Participants included 100 AYAs (60% male) with primarily hematological cancers (88%). Past year alcohol, tobacco, and cannabis use prevalence rates were 80%, 15%, and 33%, respectively. A minority (non‐users) refrained from both alcohol and tobacco (20%), while most were exclusively alcohol users (65%) or alcohol and tobacco co‐users (15%). Relative to other sub‐groups, co‐users reported more depressive and anxious symptoms, while non‐users reported more physical activity. More frequent tobacco and cannabis use were associated with more depressive and anxious symptoms, while more frequent alcohol use was associated with lower physical activity. There were no group differences or associations with sleep quality. There was considerable discordance between tobacco use self‐report, biochemical verification, and medical record documentation.

Conclusions

Substance use among AYAs is common and detrimental to mental and physical health, especially among more frequent users and co‐users, highlighting the need for early assessment and intervention.
Impact of wildfire on permafrost landscapes: A review of recent advances and future prospects
Authors: Holloway Jean E. , Lewkowicz Antoni G. , Douglas Thomas A. , Li Xiaoying , Turetsky Merritt R. , Baltzer Jennifer L. , Jin Huijun
Published: March 2020

Changes in the frequency and extent of wildfires are expected to lead to substantial and irreversible alterations to permafrost landscapes under a warming climate. Here we review recent publications (2010–2019) that advance our understanding of the effects of wildfire on surface and ground temperatures, on active layer thickness and, where permafrost is ice‐rich, on ground subsidence and the development of thermokarst features. These thermal and geomorphic changes are initiated immediately following wildfire and alter the hydrology and biogeochemistry of permafrost landscapes, including the release of previously frozen carbon. In many locations, permafrost has been resilient, with key characteristics such as active layer thickness returning to pre‐fire conditions after several decades. However, permafrost near its southern limit is losing this resiliency as a result of ongoing climate warming and increasingly common vegetation state changes. Shifts in fire return intervals, severity and extent are expected to alter the trajectories of wildfire impacts on permafrost, and to enlarge spatial impacts to more regularly include the burning of tundra areas. Modeling indicates some lowland boreal forest and tundra environments will remain resilient while uplands and areas with thin organic layers and dry soils will experience rapid and irreversible permafrost degradation. More work is needed to relate modeling to empirical studies, particularly incorporating dynamic variables such as soil moisture, snow and thermokarst development, and to identify post‐fire permafrost responses for different landscape types and regions. Future progress requires further collaboration among geocryologists, ecologists, hydrologists, biogeochemists, modelers and remote sensing specialists.
Investigation of α/γ hybrid peptide self‐assembled structures with antimicrobial and antibiofilm properties
Authors: Shankar Sudha , Singh Gurpreet , Rahim Junaid Ur , Qayum Arem , Sharma Parduman R. , Katoch Meenu , Rai Rajkishor
Published: March 2020

The present work describes the synthesis and characterization of α/γ hybrid peptides, Boc‐Phe‐γ4‐Phe‐Val‐OMe, P1; Boc‐Ala‐γ4‐Phe‐Val‐OMe, P2; and Boc‐Leu‐γ4‐Phe‐Val‐OMe, P3 together with the formation of self‐assembled structures formed by these hybrid peptides in dimethyl sulfoxide (DMSO)/water (1:1). The self‐assembled structures were characterized by infrared (IR) spectroscopy, circular dichroism (CD), and scanning electron microscopy (SEM). Further, α/γ hybrid peptide self‐assembled structures were evaluated for antibacterial properties. Among all, the self‐assembled peptide P1 exhibited the antimicrobial activity against Escherichia coli and Klebsiella pneumoniae, while self‐assembled peptide P3 inhibited the biofilms of Salmonella typhimurium and Pseudomonas aeruginosa. In this study, we have shown the significance of self‐assembled structures formed from completely hydrophobic α/γ hybrid peptides in exploring the antibacterial properties together with biofilm inhibition.
Dynamic Structure Factor and Dielectric Function of Valence Electrons in Lithium Hydride: An Inelastic X‐Ray Scattering Study at Finite Momentum Transfer
Authors: Paredes-Mellone Oscar A. , Koskelo Jaakko , Ceppi Sergio A. , Stutz Guillermo E.
Published: March 2020

The effects of electron–hole interaction in the dynamic structure factor and the complex dielectric function of valence electrons in lithium hydride at finite momentum transferqare investigated by means of inelastic X‐ray scattering (IXS) spectroscopy and ab initio theoretical methods. Calculations of and are conducted within time‐dependent density functional theory (TDDFT) in adiabatic local density approximation (ALDA) and many‐body perturbation theory (MBPT) based on the Bethe–Salpeter equation (BSE). The findings reveal that for lowqan explicit treatment of electron–hole interactions using BSE formalism slightly modifies the low‐energy structures in in comparison with ALDA results but affects strongly the macroscopic dielectric functions. A very good agreement between the experimental and theoretical and in all the range of investigatedqvalues is achieved for calculations based on BSE after taking into account the full excitonic Hamiltonian. The results demonstrate the potential of approximations based on the BSE to accurately describe the valence excitation spectra, including the near‐onset region, and the dielectric response in insulating systems, where excitonic effects are relevant.
Expanding perspectives of soil nitrification to include ammonia‐oxidizing archaea and comammox bacteria
Authors: Lu Xinda , Taylor Anne E. , Myrold David D. , Neufeld Josh D.
Published: March 2020

Catalyzed by multiple groups of phylogenetically distinct microorganisms, soil nitrification impacts ground water quality, greenhouse gas emissions, and agricultural practices. This review explores known microbial players involved in nitrification, encompassing aspects of biogeography, phylogenetic diversity, physiology, and activity. We discuss distributions and activities of ammonia‐oxidizing archaea and bacteria as they relate to environmental and edaphic factors and highlight a newly discovered role for terrestrial comammox bacteria. Ecological interactions of ammonia oxidizers and nitrite oxidizers are discussed, as are their respective contributions to N2O emissions. Given these expanding perspectives of soil nitrification, we underline the importance of combining culture‐based methods with metagenomic approaches to help address remaining knowledge gaps.
Environmental and Fish Assemblage Contrasts in Blackwater and Clearwater Streams
Authors: Colvin S. A. R. , Helms B. S. , DeVries D. R. , Feminella J. W.
Published: March 2020

We compared 15 blackwater and clearwater streams in coastal drainages of Alabama by quantifying fish assemblages and associated environmental conditions across multiple seasons and characterizing potential relationships using multivariate statistical approaches. Clearwater stream channels tended to be deeper, to have sandier substrates, and to have higher dissolved oxygen concentrations than blackwater streams. In contrast, blackwater streams showed higher dissolved organic carbon levels and higher benthic macroinvertebrate densities. Discriminant function analysis based on environmental and invertebrate data resulted in 90% discrimination between the two stream types. Nonmetric multidimensional scaling (NMDS) of seasonal fish assemblages indicated separation by stream type, with no overlap in fish assemblages of blackwater and clearwater streams in any season, and 12 (39%) of the 31 species captured were indicative of stream type. A suite of environmental and biological variables representing invertebrate density, discharge, stream size, water chemistry, and land use was correlated with NMDS axes separating fish assemblages by stream type. Fish traits were somewhat distinctive between stream types, as there were unique lie‐in‐wait predators and short‐lived species in each stream type. A fourth‐corner analysis indicated potential linkages between fishes preferring woody substrate and stream type, further suggesting that stream type may explain fish functional structure. These results emphasize the need to consider these coastal systems as biotically unique ecosystem types in conservation plans as well as to focus more attention on better understanding the diversity patterns in headwater streams within the Coastal Plains region.
Water law and climate change in the United States: A review of the legal scholarship
Authors: Craig Robin Kundis
Published: March 2020

Climate change's effects on water resources have been some of the first realities of ecological change in the Anthropocene, forcing climate change adaptation efforts even as the international community seeks to mitigate climate change. Water law has thus become one vehicle of climate change adaptation. Legal research into the intersections between climate change and water law in the United States must contend with the facts that: (a) climate change affects different parts of this large country differently; and (b) U.S. water law is itself a complicated subject, with each state having its own laws for surface water and groundwater and the federal government playing a significant role in interstate and international waters, in building and managing large water infrastructure, and in creating water rights for Native American tribes and other federal reservations. Within this complexity, legal research to date has tended to focus on the law governing surface water in the American West, enumerating various problems with the prior appropriation doctrine as the West grows hotter and drier and offering multiple suggestions to increase legal flexibility so that western water can be re‐allocated to reflect changing social–ecological realities. These suggestions extend to new, more comprehensive, and more adaptive water governance approaches. Far less legal scholarship has focused on eastern riparian rights, the various groundwater doctrines at play in the United States, or the increasing role of tribes in managing water resources, but these areas warrant future attention.

This article is categorized under:

Engineering Water > Planning Water

Human Water > Water Governance

Science of Water > Water and Environmental Change
Phosphate removal from water using alginate/carboxymethylcellulose/aluminum beads and plaster of paris
Authors: Malicevic Srdjan , Garcia Pacheco Ana Paula , Lamont Kristine , Estepa Klaudine Monica , Daguppati Prasad , van de Vegte John , Marangoni Alejandro G. , Pensini Erica
Published: March 2020

Phosphorus released in lakes due to agricultural water runoff causes eutrophication, deteriorating water quality and harming ecosystems. Two adsorbents were studied for the removal of phosphate from water: plaster of Paris powder and hydrogel beads produced using alginate, carboxymethylcellulose, and aluminum. The reaction kinetics, adsorption capacity, and ability to desorb were compared. Sorption of phosphate with either plaster of Paris or hydrogel beads was well described by the Langmuir model. In deionized water, hydrogel beads had a maximum sorption capacity of 90.5 mg 

/g dry bead with an equilibration time of approximately 24 hr. Monovalent anions (e.g., chloride) did not affect phosphorus sorption onto hydrogel beads, whereas divalent anions (e.g., sulfate) hindered sorption. In deionized water, plaster of Paris (POP) powder has a maximum capacity of 1.52 mg 

/g with an equilibrium time of less than 10 min. Sorbents can potentially be reused following phosphate desorption, and desorbed phosphate may be reused as fertilizer. At pH = 9.5, hydrogel beads desorbed up to 60% of the original amount of phosphate sorbed and lower amounts at lower pH. At pH = 2, POP powder desorbed only 35% of the initial phosphate sorbed, and desorption decreased with increasing pH.

Practitioner points

The maximum sorption capacity of plaster of Paris is 1.52 mg 

/g.

The maximum sorption capacity of hydrogel beads is 90.5 mg 

/g.

Monovalent anions do not affect phosphorus sorption, and divalent anions hinder it by ≈36%.

Sorption is well described by Langmuir isotherms (R2 > 0.98).

Hydrogel beads desorb 60% of phosphorus at pH = 9, possibly allowing phosphorus reuse.
Identity Lost and Found: Architecture and Identity Formation in Kuwait and the Gulf
Authors: Fabbri Roberto
Published: March 2020

The process of identity formation is deeply influenced by the build environment’s capacity to represent common values. In the Gulf, official narratives always praised modern buildings as the perfect representation of the impatient advancement of the society. On the other hand, the rapid transformation of the built environment, which often sacrificed the traditional old town, and the injection of ‘other’ narratives have blurred the contours of the local culture, identity and sense of place.

Focusing on Kuwait as a case study, the present text retraces the transition from the Arab medina to the conception and the construction of the modern city and how this redefined fluid notions of tradition, modernity and identity in relation with the urban environment. Since the Gulf cities experienced parallel developments in the urban form and also similar approaches to modernity and globalization, this chapter investigates the architecture produced in the second half of the twentieth century as a common denominator for the Gulf, despite the fact that it has been ignored and neglected in the past decades. Indeed, a new tangible interest, demonstrated by a series of recent cultural initiatives in Kuwait, and across the Gulf, seems to indicate how modernist architecture could be read as part of a shared Khaleeji identity in the making.
Tunnelling of charged particles from black holes
Authors: Johnson George
Published: March 2020

Abstract

We state and explain the total rate at which a charged non-rotating black hole emits charged particles, taking into account both Hawking radiation and Schwinger pair production simultaneously. We give concrete formulae for this emission rate in certain limits, with the greatest simplification occurring when the black hole is much larger than the particle’s Compton wavelength. We provide an interpretation of the result in terms of a tunnelling process, both through the black hole horizon and the surrounding electric field, and comment on how suppression due to tunnelling modifies the emission spectrum.
On the infinite gradient-flow for the domain-wall formulation of chiral lattice gauge theories
Authors: Ago Taichi , Kikukawa Yoshio
Published: March 2020

Abstract

We examine the proposal by Grabowska and Kaplan (GK) to use the infinite gradient flow in the domain-wall formulation of chiral lattice gauge theories. We consider the case of Abelian theories in detail, for which Lüscher’s exact gauge-invariant formulation is known, and we relate GK’s formulation to Lüscher’s one. The gradient flow can be formulated for the admissible U(1) link fields so that it preserves their topological charges. GK’s effective action turns out to be equal to the sum of Lüscher’s gauge-invariant effective actions for the target Weyl fermions and the mirror “fluffy” fermions, plus the so-called measure-term integrated along the infinite gradient flow. The measure-term current is originally a local(analytic) and gauge-invariant functional of the admissible link field, given as a solution to the local cohomology problem. However, with the infinite gradient flow, it gives rise to non-local(non-analytic) vertex functions which are not suppressed exponentially at large distance. The “fluffy” fermions remain as a source of non-local contribution, which couple yet to the Wilson-line and magnetic-flux degrees of freedom of the dynamical link field.
Lagos state ambulance service: a performance evaluation
Authors: Venkatraman Chinmayee , Odusola Aina Olufemi , Malolan Chenchita , Kola-Korolo Olusegun , Olaomi Oluwole , Idris Jide , Nwariaku Fiemu E.
Published: March 2020

Objectives

The mortality rate from road traffic accidents (RTAs) in Nigeria is almost double that of the USA. In Nigeria, the first emergency medical services (EMS) system was established in March 2001, The Lagos State Ambulance Service (LASAMBUS). The objectives of this study are to (1) determine the burden of RTAs in Lagos, (2) assess RTA call outcomes, and (3) analyze LASAMBUS’s response time and causes for delay.

Methodology

We reviewed completed LASAMBUS intervention forms spanning December 2017 to May 2018. We categorized the call outcomes into five groups: I. Addressed Crash, II. No Crash (False Call), III. Crash Already Addressed, IV. Did Not Respond, and V. Other. We further explored associations between the (1) causes for delay and outcomes and (2) response times and the outcomes.

Results

Overall, we analyzed 1352 intervention forms. We found that LASAMBUS did not address 53% of the RTA calls that they received. Of this, Outcome II. No Crash (False Call) accounted for 26% and Outcome III. Crash Already Addressed accounted for 22%. Self-reported causes for delay were recorded in 180 forms, representing 13.7% of the RTA burden. Traffic congestion accounted for 60% of this distribution.

Conclusion

LASAMBUS response rates are significantly lower than response rates in high-income countries such as the USA and lead to increased RTA mortality rates. Eliminating causes for delay will improve both LASAMBUS effectiveness and RTA victims’ health outcomes. Changing the public perception of LASAMBUS and standardizing LASAMBUS’ contact information will aid this as well.
Slow progressors to type 1 diabetes lose islet autoantibodies over time, have few islet antigen-specific CD8+ T cells and exhibit a distinct CD95hi B cell phenotype
Authors: Hanna Stephanie J. , Powell Wendy E. , Long Anna E. , Robinson Emma J. S. , Davies Joanne , Megson Clare , Howell Alexandra , Jones Taz J. , Ladell Kristin , Price David A. , Dayan Colin M. , Williams Alistair J. K. , Gillespie Kathleen M. , Wong F. Susan
Published: March 2020

Aims/hypothesis

The aim of this study was to characterise islet autoantibody profiles and immune cell phenotypes in slow progressors to type 1 diabetes.

Methods

Immunological variables were compared across peripheral blood samples obtained from slow progressors to type 1 diabetes, individuals with newly diagnosed or long-standing type 1 diabetes, and healthy individuals. Polychromatic flow cytometry was used to characterise the phenotypic attributes of B and T cells. Islet autoantigen-specific B cells were quantified using an enzyme-linked immunospot (ELISpot) assay and islet autoantigen-specific CD8+ T cells were quantified using peptide–HLA class I tetramers. Radioimmunoassays were used to detect islet autoantibodies. Sera were assayed for various chemokines, cytokines and soluble receptors via ELISAs.

Results

Islet autoantibodies were lost over time in slow progressors. Various B cell subsets expressed higher levels of CD95 in slow progressors, especially after polyclonal stimulation, compared with the corresponding B cell subsets in healthy donors (p < 0.05). The phenotypic characteristics of CD4+ and CD8+ T cells were similar in slow progressors and healthy donors. Lower frequencies of CD4+ T cells with a central memory phenotype (CD27int, CD127+, CD95int) were observed in slow progressors compared with healthy donors (mean percentage of total CD4+ T cells was 3.00% in slow progressors vs 4.67% in healthy donors, p < 0.05). Autoreactive B cell responses to proinsulin were detected at higher frequencies in slow progressors compared with healthy donors (median no. of spots was 0 in healthy donors vs 24.34 in slow progressors, p < 0.05) in an ELISpot assay. Islet autoantigen-specific CD8+ T cell responses were largely absent in slow progressors and healthy donors. Serum levels of DcR3, the decoy receptor for CD95L, were elevated in slow progressors compared with healthy donors (median was 1087 pg/ml in slow progressors vs 651 pg/ml in healthy donors, p = 0.06).

Conclusions/interpretation

In this study, we found that slow progression to type 1 diabetes was associated with a loss of islet autoantibodies and a distinct B cell phenotype, consistent with enhanced apoptotic regulation of peripheral autoreactivity via CD95. These phenotypic changes warrant further studies in larger cohorts to determine their functional implications.
Interobserver variability, detection rate, and lesion patterns of 68Ga-PSMA-11-PET/CT in early-stage biochemical recurrence of prostate cancer after radical prostatectomy
Authors: Miksch Jonathan , Bottke Dirk , Krohn Thomas , Thamm Reinhard , Bartkowiak Detlef , Solbach Christoph , Bolenz Christian , Beer Meinrad , Wiegel Thomas , Beer Ambros J. , Prasad Vikas
Published: March 2020

Purpose

68Ga-PSMA-11-PET/CT is increasingly used in early-stage biochemical recurrence of prostate cancer to detect potential lesions for an individualized radiotherapy concept. However, subtle findings especially concerning small local recurrences can still be challenging to interpret and are prone to variability between different readers. Thus, we analyzed interobserver variability, detection rate, and lesion patterns systematically in a homogeneous patient population with low-level biochemical recurrence.

Methods

We analyzed 68Ga-PSMA-11-PET/CTs in 116 patients with status post-prostatectomy and PSA levels up to 0.6 ng/ml. None of them received ADT or radiotherapy beforehand. Images were interpreted and blinded by two nuclear medicine physicians (R1 and R2). Findings were rated using a 5-point scale concerning local recurrence, lymph nodes, bone lesions, and other findings (1: definitely benign, 2: probably benign, 3: equivocal, 4: probably malignant, 5: definitely malignant). In findings with substantial discrepancies of 2 or more categories and/or potentially leading to differences in further patient management, a consensus reading was done with a third reader (R3). Interobserver agreement was measured by Cohens Kappa analysis after sub-categorizing our classification system to benign (1 + 2), equivocal (3), and malignant (4 + 5). Time course of PSA levels after salvage treatment of patients rated as positive (4 + 5) was analyzed.

Results

The overall detection rate (categories 4 and 5) was 50% (R1/R2, 49%/51%) and in the PSA subgroups 0–0.2 ng/ml, 0.21–0.3 ng/ml, and 0.31–0.6 ng/ml 24%/27%, 57%/57%, and 65%/68%, respectively. Local recurrence was the most common lesion manifestation followed by lymphatic and bone metastases. The overall agreement in the Cohens Kappa analysis was 0.74 between R1 and R2. For local, lymphatic, and bone sites, the agreement was 0.76, 0.73, and 0.58, respectively. PSA levels of PSMA PET/CT-positive patients after salvage treatment decreased in 75% (27/36) and increased in 25% (9/36). A decrease of PSA, although more frequent in patients with imaging suggesting only local tumor recurrence (86%, 18/21), was also observed in 67% (10/15) of patients with findings of metastatic disease.

Conclusions

In a highly homogeneous group of prostate cancer patients with early-stage biochemical recurrence after radical prostatectomy, we could show that 68Ga-PSMA-11-PET/CT has a good detection rate of 50% which is in accordance with literature, with clinically relevant findings even in patients with PSA < 0.21 ng/ml. The interobserver variability is low, particularly concerning assessment of local recurrences and lymph nodes. Therefore, PSMA-PET/CT is a robust diagnostic modality in this patient group for therapy planning.
Adipose Tissue in Multiple Symmetric Lipomatosis Shows Features of Brown/Beige Fat
Authors: Schiltz Daniel , Tschernitz Sebastian , Ortner Christine , Anker Alexandra , Klein Silvan , Felthaus Oliver , Biermann Niklas , Schreml Julia , Prantl Lukas , Schreml Stephan
Published: March 2020

Introduction

Multiple symmetric lipomatosis (MSL) (syn.: Launois–Bensaude Syndrome, benign symmetric lipomatosis) is a rare disease of fatty tissue. The pathophysiology of MSL still remains unclear, although several approaches have been described in order to understand it. Beside morphological characteristics and some molecular cell biological approaches, little is known about the histological and immunohistochemical characterization of adipose tissue from patients with MSL.

Methods

From the 45 patients with MSL in our database, 10 were included in the study. Fat tissue samples were collected from affected and unaffected areas. The forearm served as a control area as this area is not affected in MSL. The specimens were analyzed after selected stainings were taken (hematoxylin–eosin = HE, Elastica van Gieson, Ladewig, CD200, CIDEA, myf5, p107, Prdm16, Sca-1, syndecan, UCP1, MAC387, Glut4).

Results

In patients suffering from MSL, no macroscopic or microscopic morphological difference could be found between affected and unaffected adipose tissue in HE stainings. The majority of samples showed positivity for UCP1 (9/10 clinically affected tissues, 7/10 clinically unaffected tissues) and CD200.

Conclusion

Marker profiles support the hypothesis that affected adipose tissue derives from brown or beige adipose tissue rather than from white fat.

Level of Evidence IV

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
Barriers to Effective Transfusion Practices in Limited‐Resource Settings: From Infrastructure to Cultural Beliefs
Authors: Mohammed Alhassan Datti , Ntambwe Papytcho , Crawford Ana Maria
Published: March 2020

Background

Surgery and anesthesia are indivisible parts of health care, but safe and timely care requires more than operating rooms and skilled providers. One vital component of a functional surgical system is reliable blood transfusion. While almost half of all blood is donated in high‐income countries (HICs), over eighty percent of the global population lives outside of these countries. High‐income countries have on average 30 donations per 1000 people, and the average age of transfusion recipient is over 65. Most low‐income countries (LICs) have fewer than five donations per 1000 people, where maternal hemorrhage and childhood anemia are the most common indications for transfusion. In LICs, greater than 50% of blood is administered to children under 5 years of age. This study aims to snapshot, by survey, available resources for transfusion and then discusses the infrastructure and cultural barriers to optimal transfusion practice.

Methods

In January 2019, a 10‐question survey was sent electronically to physician anesthesiologists working in low‐ and middle‐income countries to examine resources and practice patterns for blood transfusion. Subsequent discussions illustrate obstacles contributing to low availability of blood products and illuminate infrastructure and cultural barriers preventing optimal transfusion practices.

Survey Results

Acquiring whole blood takes hours. Clinicians wait days to receive packed red blood cells or platelets. Fresh frozen plasma is available but untimely. For many, protocols for massive transfusion are rare, and for transfusion, ratios are nonexistent. Complete blood counts take hours, and coagulation profiles are severely delayed.

Discussion of Infrastructure and Cultural Barriers

With few voluntary, unpaid, donors and inconsistent supply of testing kits, donated blood is unsafe. Donors are seasonal for farming communities, endemic malaria areas, and student donors recruited through schools. Cultural beliefs fuel distrust. Transfusion specialists, concentrated in urban areas, see rural patients presenting late. Inadequate triaging and supervision jeopardize patients to shock. Inadequate blood storage leads to waste. Modeling systems from HICs fail to overcome hurdles faced by clinicians working with distinctive belief systems and unique patient populations.
Epidemiological Comparisons and Risk Factors for Pre‐hospital and In‐Hospital Mortality Following Traumatic Injury in Malawi
Authors: Purcell Laura N. , Mulima Gift , Reiss Rachel , Gallaher Jared , Charles Anthony
Published: March 2020

Background

In sub‐Saharan Africa, trauma is a leading cause of mortality in people less than 45 years. Injury mechanism and cause of death are difficult to characterize in the absence of pre‐hospital care and a trauma surveillance database. Pre‐hospital deaths (PHD) and in‐hospital deaths (IHD) of trauma patient were compared to elucidate comprehensive injury characteristics associated with mortality.

Methods

A retrospective, descriptive analysis of adults (≥ 13 years) presenting to Kamuzu Central Hospital in Lilongwe, Malawi, from February 2008 to May 2018 was performed. Utilizing an emergency department‐based trauma surveillance database, univariate and bivariate analysis was performed to compare patient and injury characteristics of pre‐hospital and in‐hospital deaths. A Poisson multivariate regression was performed, predicting the relative risk of PHD.

Results

Between February 2008 and May 2018, 131,020 adult trauma patients presented to KCH, with 2007 fatalities. Of those patients, 1130 (56.3%) and 877 (43.7%) were PHD and IHD, respectively. The majority were men, with a mean age of 33.4 years (SD 12.1) for PHD and 37.4 years (SD 15.5) for IHD, (p < 0.001). Head injuries (n = 545, 49.2% vs. n = 435, 49.7%) due to assaults (n = 255, 24.7% vs. n = 178, 21.8%) and motor vehicle collisions (MVC) (n = 188, 18.2% vs. n = 173, 21.2%) were the leading cause of both groups (PHD vs. IHD). Transportation to the hospital was primarily police (n = 663, 60.1%) for PHD and ambulance (n = 401, 46.4%) for IHD. Patients who were transported to KCH by the police (RR 1.97, 95% 1.52–2.55, p < 0.001) when compared to transport via minibus had an increased relative risk of PHD. Patients with a head or spine (RR 1.32, 95% CI 1.34–1.53, p < 0.001), chest (RR 1.34, 95% CI 1.11–1.62, p = 0.002) or abdomen and pelvis (RR 1.30, 95% CI 1.14–1.53, p = 0.004) when compared to extremity injury had an increased relative risk of PHD.

Conclusions

Head injury from assaults and MVC is the leading cause of PHD and IHD in Malawi. The majority of patients are transported via police if PHD. Of IHD patients, the majority are transported by ambulance, most often from outside hospitals. Both are consistent with the absence of a pre‐hospital system in Malawi. Improving pre‐hospital care, with a particular focus on head injury and strategies for vehicular injury prevention within a trauma system, will reduce adult trauma mortality in Malawi.
Towards bridging the grey digital divide: changes in internet access and its predictors from 2002 to 2014 in Germany
Authors: Huxhold Oliver , Hees Elena , Webster Noah J.
Published: March 2020

The internet is an indispensable aspect of modern society. It facilitates long distance communication, access to information, health care interventions, as well as multiple opportunities for social participation. Despite increasing pervasiveness of this technology, persistent inequalities exist in who has access to the internet. In particular, older adults lag behind in having internet access, thus putting them at risk for social exclusion. In order to gain a better understanding about the determinants of thisgrey digital divide, the current study contrasts influencing factors of internet access, comparing samples from 2002 to 2014 across age groups (40 to 54 years, 55 to 69 years and 70 to 85 years) using data from the German Ageing Survey (DEAS). Logistic regression confirmed that the likelihood of having internet access was lower with higher age at both time points. However, the percentages of people with internet access grew primarily in the middle and older age groups between 2002 and 2014. Furthermore, being male and having a higher education were both associated with greater odds of internet access. However, gender and education differences in internet access were significantly less pronounced in 2014 in contrast to 2002. Finally, both greater income and cognitive ability were associated with greater odds of internet access, while providing care for a grandchild was significantly associated with internet access only among the oldest age group. In an attempt towards bridging the grey digital divide, the current study serves as a basis for identifying groups mostly affected by this increasingly important form of social inequality.
Validation of the HIV Pre-exposure Prophylaxis Stigma Scale: Performance of Likert and Semantic Differential Scale Versions
Authors: Siegler Aaron J. , Wiatrek Sarah , Mouhanna Farah , Amico K. Rivet , Dominguez Karen , Jones Jeb , Patel Rupa R. , Mena Leandro A. , Mayer Kenneth H.
Published: March 2020

Stigma regarding HIV pre-exposure prophylaxis (PrEP) is commonly implicated as a factor limiting the scale-up of this highly effective HIV prevention modality. To quantify and characterize PrEP stigma, we developed and validated a brief HIV PrEP Stigma Scale (HPSS) among a group of 279 men who have sex with men (MSM). Scale development was informed by a theoretical model to enhance content validity. We assessed two scale versions, Semantic Differential and Likert, randomizing the order in which scales were presented to participants. Both scales demonstrated high internal consistency. The Likert scale had substantially better construct validity and was selected as the preferred option. Scale scores demonstrated construct validity through association with constructs of interest: healthcare distrust, HIV knowledge, perceived proportion of friends/partners on PrEP, perceived community evaluation of PrEP, and perceived effectiveness of PrEP. The scale accounted for 25% of the total variance in reported willingness to be on PrEP, indicating the substantial role PrEP stigma may have on decisions to initiate PrEP. Given increased efforts to roll-out PrEP, having a valid tool to determine the level and types of PrEP stigma in individuals, groups, and communities can help direct implementation plans, identify goals for stigma reduction, and monitor progress over time.
Phase 1 study to evaluate safety, tolerability and pharmacokinetics of a novel intra-tympanic administered thiosulfate to prevent cisplatin-induced hearing loss in cancer patients
Authors: Viglietta Vissia , Shi Fuxin , Hu Qi-Ying , Ren Yong , Keilty John , Wolff Heather , McCarthy Ryan , Kropp Jason , Weber Pete , Soglia John
Published: March 2020

Cisplatin is a widely used chemotherapy for the treatment of certain solid tumors. Ototoxicity and subsequent permanent hearing loss remain a serious dose-limiting side effect associated with cisplatin treatment. To date, no therapies have been approved to prevent or treat cisplatin-induced hearing loss (CIHL). Sodium thiosulfate effectively inactivates cisplatin through covalent binding and may provide protection against cisplatin-induced ototoxicity. DB-020 is being developed as a novel formulation of sodium thiosulfate pentahydrate in 1% sodium hyaluronate for intratympanic injection (IT), enabling the delivery of high concentrations of thiosulfate into the cochlea prior to cisplatin administration. In the DB-020-002 phase 1a single-ascending dose study, healthy volunteers were enrolled into 5 cohorts to receive different doses of DB-020 via IT injection. Cohorts 1–4 received unilateral injections while Cohort 5 received bilateral injections. Plasma thiosulfate pharmacokinetics was measured, and safety and audiometric data were collected throughout the study. This study has demonstrated that intratympanic administration of DB-020 results in nominal systemic increases in thiosulfate levels, hence it should not compromise cisplatin anti-tumor efficacy. Furthermore, DB-020 was safe and well tolerated with most adverse events reported as transient, of mild-to-moderate severity and related to the IT administration procedure. These results support the design and execution of the ongoing proof-of-concept study, DB-020-002, to assess otoprotection using DB-020 in cancer patients receiving cisplatin without negatively impacting cisplatin anti-tumor efficacy.
Global vulnerability of soil ecosystems to erosion
Authors: Guerra Carlos A. , Rosa Isabel M. D. , Valentini Emiliana , Wolf Florian , Filipponi Federico , Karger Dirk N. , Nguyen Xuan Alessandra , Mathieu Jerome , Lavelle Patrick , Eisenhauer Nico
Published: March 2020

Context

Soil erosion is one of the main threats driving soil degradation across the globe with important impacts on crop yields, soil biota, biogeochemical cycles, and ultimately human nutrition.

Objectives

Here, using an empirical model, we present a global and temporally explicit assessment of soil erosion risk according to recent (2001–2013) dynamics of rainfall and vegetation cover change to identify vulnerable areas for soils and soil biodiversity.

Methods

We used an adaptation of the Universal Soil Loss Equation together with state of the art remote sensing models to create a spatially and temporally explicit global model of soil erosion and soil protection. Finally, we overlaid global maps of soil biodiversity to assess the potential vulnerability of these soil communities to soil erosion.

Results

We show a consistent decline in soil erosion protection over time across terrestrial biomes, which resulted in a global increase of 11.7% in soil erosion rates. Notably, soil erosion risk systematically increased between 2006 and 2013 in relation to the baseline year (2001). Although vegetation cover is central to soil protection, this increase was mostly driven by changes in rainfall erosivity. Globally, soil erosion is expected not only to have an impact on the vulnerability of soil conditions but also on soil biodiversity with 6.4% (for soil macrofauna) and 7.6% (for soil fungi) of these vulnerable areas coinciding with regions with high soil biodiversity.

Conclusions

Our results indicate that an increasing proportion of soils are degraded globally, affecting not only livelihoods but also potentially degrading local and regional landscapes. Similarly, many degraded regions coincide with and may have impacted high levels of soil biodiversity.
Considerations about the quality assessment of travel time and travel distance distributions in transport modelling: a proposal for a standardized methodology
Authors: Pestel Eric
Published: March 2020

In travel demand modelling, trip distance distributions or trip time distributions are used to evaluate how well a model fits with observed sample data. Therefore, the comparison of distributions is an essential part in the model validation process. Despite its importance, the common modelling guidelines from the UK, the USA or Austria provide little information about the correct structure and handling of such distributions. Likewise, common statistical methods are not practicable for the validation of transport models. This lack of rules leads to individual solutions, which complicate a model validation and the comparison of models. For example, when comparing two distributions the quality indicator strongly depends on the number of classes. Therefore, guidelines for model validation need to suggest an appropriate way to determine the number of classes. The paper suggests a method for evaluating trip distance distributions and trip time distributions within the model validation process of a travel demand model. It proposes (a) indicators for a classification which consider mode-specific trip distances and trip times (b) a generic classification method based on an equiquantile class width, quality indicators for comparing two distributions and (c) to use relative frequencies instead of absolute frequencies for the calculation of the quality indicators.
Analysis of the Semantic Scope of Two Korean Terms Equivalent to English Court
Authors: Wojtasik-Dziekan Emilia
Published: March 2020

The article aims to analyze the semantic fields of two Korean terms in the field of a specialized judicial terminology, i.e.courtandtribunal, which are usually reflected in English by one hypernym termcourt. This analysis, although carried out on limited Korean data, is intended to indicate the differences between the use of these two different Korean terms and to indicate the reasons whycourtis currently the most common English equivalent. At the same time, the author, by pointing to the historical and cultural background, explains the reasons why the termcourtis not always correct. The methods used in compiling the data are to highlight differences in the semantics of Korean terms covered by an English hypernymcourt.