bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural validation of facial skin using optical coherence tomography: A descriptive study
Authors: Jerjes Waseem , Hamdoon Zaid , Hopper Colin
Published: September 2019

Background

In this immediate ex vivo study, we aimed to identify the structures of normal and pathological facial skin using optical coherence tomography (OCT) and compared them to the gold standard histopathology.

Material and Methods

A total of 53 patients, with 57 suspicious facial lesions, participated in this study. A set of variables have been highlighted by the pathologist to represent the minimum unique features that could be used to diagnose a skin pathology have been included in a checklist. One pathologist used this checklist while examining the histopathology slides and one clinician while examining the OCT images. The data from both checklists have been reviewed and compared.

Results

Optical coherence tomography's overall accuracy in diagnosing AK was 83%. Best accuracy was achieved in diagnosing BCC and was 97%, while it was 85% for cutaneous SCC. OCT failed to diagnose LM with an accuracy of 33.3% based on the two parameters of the pathology checklist, while it was 81% for malignant melanoma.

Conclusion

This study proved the success of OCT in identifying structural changes in normal and pathological facial skin. Further studies to prove its usefulness in vivo are recommended.
Venezuela on the Edge of Bankruptcy: Prospects for Political Change
Authors: Toraldo Sara
Published: September 2019

Venezuela, a South American petro-giant and the home of the Bolivarian socialist experiment, is in the grip of a grave crisis and an unprecedented political and institutional conflict, which has led to profound economic and social paralysis and a food and health emergency. As of 2019, Venezuela has the highest rate of inflation in the world and is struggling with an economic and social crisis characterised by violence and extreme poverty. In a paradoxical political situation, despite the crisis, the incumbent president Nicolas Maduro refuses to relinquish power while a new figure, Juan Guaidò, virtually unknown a year ago, having proclaimed himself president in January 2019, has been recognised politically by 54 nations, and is seeking a way out of the country’s ills. In the first quarter of 2019 alone in Venezuela, 96% of companies had to drastically reduce their staffing levels and commercial activities, while the average salary of a worker now corresponds to about four euros a month. In addition, in the last twenty years, i.e. since the arrival in power of the previous president, Hugo Chavez, four fifths of Venezuelan companies have closed down or ceased operating after being nationalised. Lastly, 84% of those who once had employment have now lost it. What the solutions to this situation may consist of is hard to say. This brief paper will look at the series of social and cultural obstacles that hamper any form political change. Cultural and social changes that can help resolve the current political and institutional conflict as soon as possible are required. The country has the largest oil reserves in the world, put at 296.5 billion barrels, and the fourth largest natural gas reserves in the world. In addition, it has the third largest reserves of fresh water on the planet and even possesses huge mineral resources, including gold and diamonds. Despite the variety of resources available, the Venezuelan economy is weighed down by the socialist policies of the government which has neither opened up to more liberal economic policies nor diversified economic investment, thus consolidating the country’s complete dependence on petroleum exports, which now account for 96% of the income from exports and 50% of state revenues.
Control of M/Cox-2/s make-to-stock systems
Authors: Yücel Özgün , Bulut Önder
Published: September 2019

This study considers a make-to-stock production system with multiple identical parallel servers, fixed production start-up costs and lost sales. Processing times are assumed to be two-phase Coxian random variables that allows us to model the systems having rework or remanufacturing operations. First, the dynamic programming formulation is developed and the structure of the optimal production policy is characterized. Due to the highly dynamic nature of the optimal policy, as a second contribution we propose an easy-to-apply production policy. The proposed policy makes use of the dynamic state information and controlled by only two parameters. We test the performance of the proposed policy at several instances and reveal that it is near optimal. We also assess the value of dynamic state information in general by comparing the proposed policy with the well-known static inventory position based policy.
Ellipsometry, reflectance, and photoluminescence of nanocrystalline CuCl thin films on silicon
Authors: Humlíček Josef , Kuldová Karla , Krumpolec Richard , Cameron David C.
Published: September 2019

The authors have used sequential pulsed vapor deposition to prepare thin films of copper(I) chloride (CuCl) on silicon. The films are nanocrystalline and show a very strong ultraviolet luminescence. The excitonic response and corresponding luminescent properties make these films promising for new short-wavelength photonic/photoelectronic devices. The authors have undertaken systematic studies of these films, using the potential of multiple-angle-of-incidence spectroellipsometry with a rotating compensator, normal-incidence reflectance with small illuminated spots, and photoluminescence with high spatial resolution. The silicon substrate presents specific problems in the interpretation of the ellipsometric and reflectance spectra, as the excitonic multiplets of CuCl are close to the E1 interband spectral structure of Si. The authors discuss appropriate procedures to isolate the response of the thin films. In addition, since the coverage of the substrates typically shows inhomogeneity, care has to be taken in accounting for its presence. A consistent picture of the passive and active excitonic response of the films results from the multitude of experimental techniques used.
Relationship between cochlear mechanics and speech-in-noise reception performance
Authors: Otsuka Sho , Nakagawa Seiji , Furukawa Shigeto
Published: September 2019

Some normal-hearing listeners report difficulties in speech perception in noisy environments, and the cause is not well understood. The present study explores the correlation between speech-in-noise reception performance and cochlear mechanical characteristics, which were evaluated using a principal component analysis of the otoacoustic emission (OAE) spectra. A principal component, specifically a characteristic dip at around 2–2.5 kHz in OAE spectra, correlated with speech reception thresholds in noise but not in quiet. The results suggest that subclinical cochlear dysfunction specifically contributes to difficulties in speech perception in noisy environments, which is possibly a new form of “hidden hearing deficits.”
Membrane Fluidity of Saccharomyces cerevisiae from
Huangjiu
(Chinese Rice Wine) Is Variably Regulated by
OLE1
To Offset the Disruptive Effect of Ethanol
Authors: Yang Yijin , Xia Yongjun , Hu Wuyao , Tao Leren , Ni Li , Yu Jianshen , Ai Lianzhong
Published: September 2019

Yeasts with superior ethanol tolerance are desirable for winemakers and wine industries. In our previous work, strain F23 was evolved with superior ethanol tolerance and fermentation activity to improve the flavor profiles of Chinese rice wine. Therefore, exploring the genomic variations and ethanol tolerance mechanism of strain F23 could contribute to an understanding of its effect on the flavor characteristics in the resulting Chinese rice wine. The cellular membrane plays a vital role in the ethanol tolerance of yeasts; however, how the membrane is regulated to fight the toxic effect of ethanol remains to be elucidated. This study suggests that the membrane fluidity is variably regulated by
OLE1
to offset the disruptive effect of ethanol. Current work will help develop more ethanol-tolerant yeast strains for wine industries and contribute to a deep understanding of its high flavor-producing ability.
Host CARD11 Inhibits Newcastle Disease Virus Replication by Suppressing Viral Polymerase Activity in Neurons
Authors: Wang Wenbin , Chang Xudong , Yao Wei , Wei Ning , Huo Na , Wang Yanhong , Wei Qiaolin , Liu Haijin , Wang Xinglong , Zhang Shuxia , Yang Zengqi , Xiao Sa
Published: September 2019

Newcastle disease virus (NDV) substantially impacts the poultry industry worldwide and causes viral encephalitis and neurological disorders leading to brain damage, paralysis, and death. The mechanism of interaction between this neurotropic virus and the avian central nervous system (CNS) is largely unknown. Here, we report that host protein CARD11 presented brain-specific upregulated expression that inhibited NDV replication, which was not due to CARD11-Bcl10-MALT1 (CBM) complex-triggered activation of its downstream signaling pathways. The inhibitory mechanism of viral replication is through the CARD11 CC1 domain, and the viral large polymerase protein (L) competitively interacts with the X domain of the viral phosphoprotein (P), which hampers the P-L interaction, suppressing the viral polymerase activity and viral replication. An
in vivo
study indicated that CARD11 alleviated neuropathological lesions and reduced viral replication in chicken brains. These results provide insight into the interaction between NDV infection and the host defense in the CNS and a potential antiviral target for viral neural diseases.
Distinct Chemotaxis Protein Paralogs Assemble into Chemoreceptor Signaling Arrays To Coordinate Signaling Output
Authors: O’Neal Lindsey , Gullett Jessica M. , Aksenova Anastasia , Hubler Adam , Briegel Ariane , Ortega Davi , Kjær Andreas , Jensen Grant , Alexandre Gladys
Published: September 2019

The assembly of chemotaxis receptors and signaling proteins into polar arrays is universal in motile chemotactic bacteria. Comparative genome analyses indicate that most motile bacteria possess multiple chemotaxis signaling systems, and experimental evidence suggests that signaling from distinct chemotaxis systems is integrated. Here, we identify one such mechanism. We show that paralogs from two chemotaxis systems assemble together into chemoreceptor arrays, forming baseplates comprised of proteins from both chemotaxis systems. These mixed arrays provide a straightforward mechanism for signal integration and coordinated response output from distinct chemotaxis systems. Given that most chemotactic bacteria encode multiple chemotaxis systems and the propensity for these systems to be laterally transferred, this mechanism may be common to ensure chemotaxis signal integration occurs.
Stretched, mangled, and torn: Responses of the Ediacaran fossil Dickinsonia to variable forces
Authors: Evans Scott D. , Huang Wei , Gehling Jim G. , Kisailus David , Droser Mary L.
Published: September 2019

Dickinsonia is one of the oldest macroscopic metazoans in the fossil record. Determining the biological characters of this extinct taxon is critical to our understanding of the early evolution of life. Preservation of abundant specimens from the Ediacara Member (Rawnsley Quartzite), South Australia, in a variety of taphonomic states allows the unparalleled opportunity to compare the biomechanical responses of Dickinsonia tissue to various forces with those typical of modern organisms. Dickinsonia are found as lifted, transported, folded, rolled, ripped, and expanded or contracted individuals, while maintaining diagnostic morphology. This suite of characters indicates that Dickinsonia was composed of material that was flexible, difficult to rip, and capable of elastic and plastic deformation. While none of these traits are diagnostic of a single biomaterial component, we find many similarities with modern biopolymers, particularly collagen, keratin, and elastin. Maintenance of significant relief following complete tearing suggests that Dickinsonia was composed of relatively thick tissues, signifying higher oxygen requirements than previously hypothesized. The ability to be transported and still be preserved as recognizable fossils is unique amongst the Ediacara Biota and demonstrates that Dickinsonia was a taphonomic elite. Combined with discovery in multiple environmental settings, this indicates that the absence of Dickinsonia represents the likely extinction of this organism prior to the Nama assemblage, possibly due to a decrease in the global availability of oxygen in the latest Ediacaran.
Constraining the maximum depth of brittle deformation at slow- and ultraslow-spreading ridges using microseismicity
Authors: Grevemeyer Ingo , Hayman Nicholas W. , Lange Dietrich , Peirce Christine , Papenberg Cord , Van Avendonk Harm J.A. , Schmid Florian , de La Peña Laura Gómez , Dannowski Anke
Published: September 2019

The depth of earthquakes along mid-ocean ridges is restricted by the relatively thin brittle lithosphere that overlies a hot, upwelling mantle. With decreasing spreading rate, earthquakes may occur deeper in the lithosphere, accommodating strain within a thicker brittle layer. New data from the ultraslow-spreading Mid-Cayman Spreading Center (MCSC) in the Caribbean Sea illustrate that earthquakes occur to 10 km depth below seafloor and, hence, occur deeper than along most other slow-spreading ridges. The MCSC spreads at 15 mm/yr full rate, while a similarly well-studied obliquely opening portion of the Southwest Indian Ridge (SWIR) spreads at an even slower rate of ∼8 mm/yr if the obliquity of spreading is considered. The SWIR has previously been proposed to have earthquakes occurring as deep as 32 km, but no shallower than 5 km. These characteristics have been attributed to the combined effect of stable deformation of serpentinized mantle and an extremely deep thermal boundary layer. In the context of our MCSC results, we reanalyze the SWIR data and find a maximum depth of seismicity of 17 km, consistent with compilations of spreading-rate dependence derived from slow- and ultraslow-spreading ridges. Together, the new MCSC data and SWIR reanalysis presented here support the hypothesis that depth-seismicity relationships at mid-ocean ridges are a function of their thermal-mechanical structure as reflected in their spreading rate.
Scratching the surface: Footprint of a late Carboniferous ice sheet
Authors: Le Heron D.P. , Dietrich P. , Busfield M.E. , Kettler C. , Bermanschläger S. , Grasemann B.
Published: September 2019

Field observations in conjunction with aerial images from an unmanned aerial vehicle were used to create the first map of a glacial unconformity underlying the late Carboniferous Dwyka Group of South Africa. Crosscutting relationships reveal that the glacial unconformity at Oorlogskloof, in which flutes, grooves, and striae were ploughed into unconsolidated sand, formed in a three-phased process charting a periodic shift in the locus of subglacial erosion. The unconformity formed by a periodically decoupled ice sheet in a probable tidewater setting. This model contrasts with earlier views that the structures simply record progressive ice-margin liftoff during transgression, and they provide unique insight into the complex temporal development of a 300 Ma subglacial environment.
Characteristics and changes in characteristics of women and babies admitted to residential parenting services in New South Wales, Australia in the first year following birth: a population-based data linkage study 2000–2012
Authors: Dahlen Hannah G , Thornton Charlene , Fowler Cathrine , Mills Robert , O'Loughlin Grainne , Smit Jenny , Schmied Virginia
Published: September 2019

Objective

To examine the characteristics of women and babies admitted to the residential parenting services (RPS) of Tresillian and Karitane in the first year following birth.

Design

A linked population data cohort study was undertaken for the years 2000–2012.

Setting

New South Wales (NSW), Australia.

Participants

All women giving birth and babies born in NSW were compared with those admitted to RPS.

Results

During the time period there were a total of 1 097 762 births (2000–2012) in NSW and 32 991 admissions to RPS. Women in cohort 1: (those admitted to RPS) were older at the time of birth, more likely to be admitted as a private patient at the time of birth, be born in Australia and be having their first baby compared with women in cohort 2 (those not admitted to an RPS). Women admitted to RPS experienced more birth intervention (induction, instrumental birth, caesarean section), had more multiple births and were more likely to have a male infant. Their babies were also more likely to be resuscitated and have experienced birth trauma to the scalp. Between 2000 and 2012 the average age of women in the RPS increased by nearly 2 years; their infants were older on admission and women were less likely to smoke. Over the time period there was a drop in the numbers of women admitted to RPS having a normal vaginal birth and an increase in women having an instrumental birth.

Conclusion

Women who access RPS in the first year after birth are more socially advantaged and have higher birth intervention than those who do not, due in part to higher numbers birthing in the private sector where intervention rates are high. The rise in women admitted to RPS (2000–2012) who have had instrumental births is intriguing as overall rates did not increase.
Use and reporting of experience-based codesign studies in the healthcare setting: a systematic review
Authors: Green Theresa , Bonner Ann , Teleni Laisa , Bradford Natalie , Purtell Louise , Douglas Clint , Yates Patsy , MacAndrew Margaret , Dao Hai Yen , Chan Raymond Javan
Published: September 2019

Background

Experience-based codesign (EBCD) is an approach to health service design that engages patients and healthcare staff in partnership to develop and improve health services or pathways of care. The aim of this systematic review was to examine the use (structure, process and outcomes) and reporting of EBCD in health service improvement activities.

Methods

Electronic databases (MEDLINE, CINAHL, PsycINFO and The Cochrane Library) were searched to identify peer-reviewed articles published from database inception to August 2018. Search terms identified peer-reviewed English language qualitative, quantitative and mixed methods studies that underwent independent screening by two authors. Full texts were independently reviewed by two reviewers and data were independently extracted by one reviewer before being checked by a second reviewer. Adherence to the 10 activities embedded within the eight-stage EBCD framework was calculated for each study.

Results

We identified 20 studies predominantly from the UK and in acute mental health or cancer services. EBCD fidelity ranged from 40% to 100% with only three studies satisfying 100% fidelity.

Conclusion

EBCD is used predominantly for quality improvement, but has potential to be used for intervention design projects. There is variation in the use of EBCD, with many studies eliminating or modifying some EBCD stages. Moreover, there is no consistency in reporting. In order to evaluate the effect of modifying EBCD or levels of EBCD fidelity, the outcomes of each EBCD phase (ie, touchpoints and improvement activities) should be reported in a consistent manner.

Trial registration number

CRD42018105879.
Synthesis, properties, and bioapplications of multifunctional gadolinium orthophosphate hollow spheres
Authors: Zhang Fangbo , Du Jie , Liu Jing , Li Jinghan , Lu Yaxian , Wang Guojing , Li Shumei , Zhang Cuimiao , Jia Guang
Published: September 2019

In this paper, gadolinium orthophosphate (GdPO4) hollow spheres with good luminescent properties, better drug loading and sustainable release have been synthesized by a template-oriented route. The precursor with core–shell structure was facilely prepared by a homogeneous precipitation and followed solvothermal method with 3-aminophenol-formaldehyde (APF) resin spheres as template. Subsequently, the APF template was eliminated and the crystalline GdPO4 hollow spheres were obtained after an annealing process. The structure, morphology, and formation process of the as-obtained GdPO4 hollow spheres have been investigated in detail. It is worth noting that lanthanide activator ions doped GdPO4 can perform optical and MRI dual-mode imaging functions. Moreover, the as-obtained GdPO4 hollow spheres exhibit good drug loading and sustained drug release behaviors. The unique hollow structure, dual-mode optical and MRI imaging capabilities, and good drug loading/release patterns enable the as-synthesized products to have enormous potential in bioimaging, drug delivery, and disease diagnosis.
Stochastic resonance in asymmetric time-delayed bistable system under multiplicative and additive noise and its applications in bearing fault detection
Authors: He Lifang , Hu Dayun , Zhang Gang , Lu Siliang
Published: September 2019

The asymmetric bistable system with time delays in the feedback force and random force under multiplicative and additive Gaussian noise is studied. Using the small time delay approximation approach and time-delayed Fokker–Planck equations (FPE), the signal-to-noise ratio (SNR) of the proposed stochastic system is obtained. The stochastic resonance (SR) phenomena influenced by parameters — including system parameters [Formula: see text], [Formula: see text], asymmetry parameter [Formula: see text], time delay [Formula: see text], strength [Formula: see text] of the time-delayed feedback, noise intensities [Formula: see text] and [Formula: see text] of multiplicative and additive noise, and correlation strength [Formula: see text] between two noises, are also analyzed by numerical simulations. Results demonstrate that the SR performance of the asymmetric bistable system is superior to one symmetric bistable system. Besides, both time delay and strength of time-delayed feedback could enhance the SR to some extent. Then, the asymmetric time-delayed bistable SR (ATDBSR) method is used to the bearing fault diagnosis. The engineering applications of the ATDBSR method are realized and the value of the method is verified by effective experimental results.
Deposition of molybdenum nitride thin layers on substrates of stainless steel AISI304 using a Mather-type of plasma focus device
Authors: Al-Hawat Sh. , Akel M. , Abdallah B. , Kharoub M. Abu
Published: September 2019

This study focuses on effects of number of shots and the distance from the top of anode on Mo–N deposition process on the surfaces of AISI304 samples using a low energy (2.8 kJ) plasma focus device (AECS PF-1) at room temperature. The structural, morphological, elemental composition, surface roughness and micro-hardness properties of treated surfaces were investigated versus the number of shots and the axial distance from the anode. The obtained XRD spectra show that some of the treated surfaces were in crystalline phase with [Formula: see text]-Mo2N (FCC) structure (at 3 cm with 10–40 shots and at 5 cm with 30 and 40 shots) and some others had amorphous structure at 5 cm with 10 and 20 shots and at 7 cm with 10–40 shots. SEM images indicate that the thermal effect occurred at 3 cm and the deposition process of Mo–N at 5 cm and 7 cm from the anode with an increase in number of shots. The atomic ratio for nitrogen was 10.62%, 12.88%, and for molybdenum it was 0.23%, 3.36% at 3 cm, respectively. The atomic ratio for nitrogen has achieved 14.95% and 22.17%, however, the atomic ratio for molybdenum was 2.11% and 7.17 % at 5 cm, respectively. The surface roughness and size of grains on the surface of deposited layers were investigated by AFM analysis. Furthermore, the variation in the micro-hardness of the Mo–N thin layers deposited by different number of shots at different distances from the tip of anode was explained, qualitatively, on the basis of morphological characteristics of the thin layers. The decreasing rates of hardness in the case of 10 shots were 146%, 117% and 112%, and at 40 shots were 237%, 149% and 141% with the increasing of distances 3, 5 and 7 cm, respectively.
Structural, magnetic and dielectric studies of siderite nano-particles synthesized by hydrothermal method
Authors: Oza Mahatta , Jethva H. O. , Kanchan D. K. , Joshi H. H. , Joshi M. J.
Published: September 2019

Siderite or ferrous carbonate [Formula: see text] is a well-known mineral and finds applications in various fields such as dietary supplement to treat anemia and in petroleum drilling fluids for [Formula: see text] removal. The FeCO3 nano-particles are synthesized by hydrothermal method using aqueous solutions of iron sulfate, ascorbic acid and ammonium carbonate with a molar ratio of 1:1:3, respectively, and heating at [Formula: see text]C for 1.5 h in Teflon-lined stainless steel autoclave. The recovered sample is characterized by several techniques. The powder XRD indicates the hexagonal crystal system and the average crystallite size of 17.32 nm are obtained from the Scherrer’s formula and 18.98 nm is obtained from the Williamson and Hall formula. The TEM images suggest the spherical nature of the nano-particles. The EDX confirms the elemental presence of iron, carbon and oxygen. The impedance and dielectric studies are carried out within 20 Hz–2 MHz range at room temperature. The complex impedance plot, i.e. the Nyquist plot, is composed of one semicircle indicating the contribution from the grain only. The Jonscher’s power-law is applied to AC conductivity data. The VSM data at room temperature and at low temperature, i.e. 20–300 K range, suggests a weak antiferromagnetic nature of the sample.
Comparative Evaluation of User Perceived Quality Assessment of Design Strategies for HTTP-based Adaptive Streaming
Authors: Bhargava Ayush , Martin James , Babu Sabarish V.
Published: September 2019

HTTP-based Adaptive Streaming (HAS) is the dominant Internet video streaming application. One specific HAS approach, Dynamic Adaptive Streaming over HTTP (DASH), is of particular interest, as it is a widely deployed, standardized implementation. Prior academic research has focused on networking and protocol issues, and has contributed an accepted understanding of the performance and possible performance issues in large deployment scenarios. Our work extends the current understanding of HAS by focusing directly on the impacts of choice of the video quality adaptation algorithm on end-user perceived quality. In congested network scenarios, the details of the adaptation algorithm determine the amount of bandwidth consumed by the application as well as the quality of the rendered video stream. HAS will lead to user-perceived changes in video quality due to intentional changes in quality video segments, or unintentional perceived quality impairments caused by video decoder artifacts such as pixelation, stutters, or short or long stalls in the rendered video when the playback buffer becomes empty. The HAS adaptation algorithm attempts to find the optimal solution to mitigate the conflict between avoiding buffer stalls and maximizing video quality. In this article, we present results from a user study that was designed to provide insights into “best practice guidelines” for a HAS adaptation algorithm. Our findings suggest that a buffer-based strategy might provide a better experience under higher network impairment conditions. For the two network scenarios considered, the buffer-based strategy is effective in avoiding stalls but does so at the cost of reduced video quality. However, the buffer-based strategy does yield a lower number of quality switches as a result of infrequent bitrate adaptations. Participants in buffer-based strategy do notice the drop in video quality causing a decrease in perceived QoE, but the perceived levels of video quality, viewer frustration, and opinions of video clarity and distortion are significantly worse due to artifacts such as stalls in capacity-based strategy. The capacity-based strategy tries to provide the highest video quality possible but produces many more artifacts during playback. The results suggest that player video quality has more of an impact on perceived quality when stalls are infrequent. The study methodology also contributes a unique method for gathering continuous quantitative subjective measure of user perceived quality using a Wii remote.
Proteomics analysis of the matrisome from MC38 experimental mouse liver metastases
Authors: Yuzhalin Arseniy E. , Lim Su Yin , Gordon-Weeks Alex N. , Fischer Roman , Kessler Benedikt M. , Yu Dihua , Muschel Ruth J.
Published: September 2019

Dissemination of primary tumors to distant anatomical sites has a substantial negative impact on patient prognosis. The liver is a common site for metastases from colorectal cancer, and patients with hepatic metastases have generally much shorter survival, raising a need to develop and implement novel strategies for targeting metastatic disease. The extracellular matrix (ECM) is a meshwork of highly crosslinked, insoluble high-molecular-mass proteins maintaining tissue integrity and establishing cell–cell interactions. Emerging evidence identifies the importance of the ECM in cancer cell migration, invasion, intravasation, and metastasis. Here, we isolated the ECM from MC38 mouse liver metastases using our optimized method of mild detergent solubilization followed by biochemical enrichment. The matrices were subjected to label-free quantitative mass spectrometry analysis, revealing proteins highly abundant in the metastatic matrisome. The resulting list of proteins upregulated in the ECM significantly predicted survival in patients with colorectal cancer but not other cancers with strong involvement of the ECM component. One of the proteins upregulated in liver metastatic ECM, annexin A1, was not previously studied in the context of cancer-associated matrisome. Here, we show that annexin A1 was markedly upregulated in colon cancer cell lines compared with cancer cells of other origin and also over-represented in human primary colorectal lesions, as well as hepatic metastases, compared with their adjacent healthy tissue counterparts. In conclusion, our study provides a comprehensive ECM characterization of MC38 experimental liver metastases and proposes annexin A1 as a putative target for this disease.

NEW & NOTEWORTHY Here, the authors provide an extensive proteomics characterization of murine colorectal cancer liver metastasis matrisome (the ensemble of all extracellular matrix molecules). The findings presented in this study may enable identification of therapeutic targets or biomarkers of hepatic metastases.
The IBD-associated long noncoding RNA IFNG-AS1 regulates the balance between inflammatory and anti-inflammatory cytokine production after T-cell stimulation
Authors: Rankin Carl Robert , Shao Ling , Elliott Julie , Rowe Lorraine , Patel Ami , Videlock Elizabeth , Benhammou Jihane N. , Sauk Jenny S. , Ather Nimah , Corson Melissa , Alipour Omeed , Gulati Alakh , Pothoulakis Charalabos , Padua David Miguel
Published: September 2019

The inflammatory bowel diseases (IBD) are a complex set of chronic gastrointestinal inflammatory conditions arising from the interplay of genetic and environmental factors. This study focuses on noncoding RNA transcripts as potential mediators of IBD pathophysiology. One particular gene, interferon γ-antisense 1 ( IFNG-AS1), has been consistently observed to be elevated in the intestinal mucosa of patients with actively inflamed IBD versus healthy controls. This study builds on these observations, demonstrating that the second splice variant is specifically altered, and this alteration even stratifies within inflamed patients. With the use of a CRISPR-based overexpression system, IFNG-AS1 was selectively overexpressed directly from its genomic loci in T cells. An unbiased mRNA array on these cells identified a large increase in many inflammatory cytokines and a decrease in anti-inflammatory cytokines after IFNG-AS1 overexpression. Media from T cells overexpressing IFNG-AS1 elicited an inflammatory signaling cascade in primary human peripheral blood mononuclear cells, suggesting the potential functional importance of IFNG-AS1 in IBD pathophysiology. The significance of these results is amplified by studies suggesting that a single-nucleotide polymorphism in IFNG-AS1, rs7134599, was associated with both subtypes of patients with IBD independently of race.

NEW & NOTEWORTHY Long noncoding RNAs are an emerging field of inflammatory bowel disease (IBD) research. This study mechanistically analyzes the role of a commonly upregulated gene in IBD and shows IFNG-AS1 as a mediator of an inflammatory signaling cascade.
Renal SGLT mRNA expression in human health and disease: a study in two cohorts
Authors: Srinivasan Sridhar Vikas , Ambinathan Jaya Prakash N. , Kretzler Matthias , Pyle Laura L. , Bjornstad Petter , Eddy Sean , Cherney David Z. , Reich Heather N. ,   European Renal cDNA Bank (ERCB);,   Nephrotic Syndrome Study Network (NEPTUNE)
Published: September 2019

Pharmacological Na+-glucose linked cotransporter (SGLT)2 inhibition is being examined as a renal protection strategy in nondiabetic chronic kidney disease. We quantified renal SGLT mRNA expression in healthy controls (HC), glomerulonephritis (GN), and diabetic kidney disease (DKD) to identify differences in expression across a spectrum of renal diseases. mRNA expression of SGLT1 and SGLT2 in renal tubules and glomeruli, obtained using microdissection and microarray techniques, was evaluated in two large cohorts. The European Renal cDNA bank included HC, GN, and DKD (98 glomeruli and 93 tubulointerstitium). The Nephrotic Syndrome Study Network cohort included 124 adults with membranous nephropathy, minimal change disease, focal segmental glomerulosclerosis, and IgA nephropathy. Within the European Renal cDNA bank, SGLT2 tubular and glomerular log2 mRNA expression significantly differed across HC, GN, and DKD ( P = 0.0009 and P = 0.0004), with the highest expression in HC. Within the Nephrotic Syndrome Study Network, there were no differences in SGLT log2 mRNA expression across GN subtypes. Tubular SGLT2 log2 mRNA expression positively correlated with estimated glomerular filtration rate (by the Modification of Diet in Renal Disease Study equation) and glycated hemoglobin ( r = 0.33 and 0.34, P < 0.05) and inversely correlated with interstitial fibrosis ( r = −0.21, P < 0.05). In conclusion, SGLT2 mRNA expression was lower in DKD compared with HC or GN and inversely related to interstitial fibrosis. The relationships between SGLT mRNA, protein expression, and transporter activity require further elucidation.
Shortening of airway smooth muscle is modulated by prolonging the time without simulated deep inspirations in ovine tracheal strips
Authors: Gazzola Morgan , Khadangi Fatemeh , Clisson Marine , Beaudoin Jonathan , Clavel Marie-Annick , Bossé Ynuk
Published: September 2019

The shortening of airway smooth muscle (ASM) is greatly affected by time. This is because stimuli affecting ASM shortening, such as bronchoactive molecules or the strain inflicted by breathing maneuvers, not only alter quick biochemical processes regulating contraction but also slower processes that allow ASM to adapt to an ever-changing length. Little attention has been given to the effect of time on ASM shortening. The present study investigates the effect of changing the time interval between simulated deep inspirations (DIs) on ASM shortening and its responsiveness to simulated DIs. Excised tracheal strips from sheep were mounted in organ baths and either activated with methacholine or relaxed with isoproterenol. They were then subjected to simulated DIs by imposing swings in distending stress, emulating a transmural pressure from 5 to 30 cmH2O. The simulated DIs were intercalated by 2, 5, 10, or 30 min. In between simulated DIs, the distending stress was either fixed or oscillating to simulate tidal breathing. The results show that although shortening was increased by prolonging the interval between simulated DIs, the bronchodilator effect of simulated DIs (i.e., the elongation of the strip post- vs. pre-DI) was not affected, and the rate of re-shortening post-simulated DIs was decreased. As the frequency with which DIs are taken increases upon bronchoconstriction, our results may be relevant to typical alterations observed in asthma, such as an increased rate of re-narrowing post-DI.

NEW & NOTEWORTHY The frequency with which patients with asthma take deep inspirations (DIs) increases during bronchoconstriction. This in vitro study investigated the effect of changing the time interval between simulated DIs on airway smooth muscle shortening. The results demonstrated that decreasing the interval between simulated DIs not only decreases shortening, which may be protective against excessive airway narrowing, but also increases the rate of re-shortening post-simulated DIs, which may contribute to the increased rate of re-narrowing post-DI observed in asthma.
Experimental Study on Seismic Strengthening of Confined Masonry Walls Using RPC
Authors: Wang Xin , Li Shuming , Wu Zhenli , Bu Fanyang , Wang Fei
Published: September 2019

Masonry structures without effective reinforcement are vulnerable to seismic excitation. An innovative strengthening technique was proposed for damaged and undamaged masonry walls. Six confined masonry units with two aspect ratios were tested under in-plane lateral cyclic loading, which consisted of two control walls, two original walls strengthened with reactive powder concrete (RPC-1), and two damaged walls repaired with RPC (RPC-2). The results of the specimens retrofitted with RPC demonstrated that the proposed technique significantly enhanced the seismic performance of masonry walls in terms of lateral strength, ductility, and energy dissipation. Furthermore, the two repaired specimens had a better distributed cracking pattern than the two strengthened specimens. The analysis of the results leads to a better understanding of the effect and mechanism of RPC seismic retrofitting for confined masonry walls.
A Modern Approach to Minimally Invasive Surgery and Laparoscopic Sterilization in a Chimpanzee
Authors: Newcomb Laura K. , Kruse Meghan A. , Minter Larry J. , Sobolewski Craig J.
Published: September 2019

We present the case of Ruby, a 21-year-old hand-reared chimpanzee (Pan troglodytes) who had an obstetric history significant for a premature stillborn infant that was conceived while on oral contraceptive pills, followed by a full term healthy delivery complicated by neonatal demise attributed to inappropriate maternal care. She was recommended for permanent sterilization due to her history of conception while on oral contraceptives. She underwent uncomplicated laparoscopic bilateral tubal ligation. Due to the similar anatomy to humans, human OB/GYN surgical consultants were used. The objective of this case report is to describe a modern technique for approaching and employing laparoscopic surgery in primates. Minimally invasive surgery allows for faster recovery and fewer complications, and has become the preferred approach for surgical intervention in many animals. The information presented in this case report can be expanded to benefit not only Chimpanzees but other large primate species as well. However, subtle anatomical differences among species must be recognized in order to be carried out safely.
The PLASMIC Score May Be Useful in the Early Diagnosis of Complement-Mediated Thrombotic Microangiopathy via Early Exclusion of Thrombotic Thrombocytopenic Purpura
Authors: Lu Edwin , Moore Willie
Published: September 2019

Complement-mediated thrombotic microangiopathy is a rare form of thrombotic microangiopathy but has high rates of mortality and morbidity. Effective treatment exists with eculizumab for this condition, but administration of treatment is often delayed because of overlapping symptoms with other causes of thrombotic microangiopathy. We present a case of a 78-year-old male who was eventually diagnosed with complement-mediated thrombotic microangiopathy. We also discuss the use of the PLASMIC scoring model to assist in more rapid diagnosis and discernment between various thrombotic microangiopathies.
ImmunoPET, [64Cu]Cu-DOTA-Anti-CD33 PET-CT, Imaging of an AML Xenograft Model
Authors: Srideshikan Sargur Madabushi , Brooks Jamison , Zuro Darren , Kumar Bijender , Sanchez James , Echavarria Parra Liliana , Orellana Marvin , Vishwasrao Paresh , Nair Indu , Chea Junie , Poku Kofi , Bowles Nicole , Miller Aaron , Ebner Todd , Molnar Justin , Rosenthal Joseph , Vallera Daniel A. , Wong Jeffrey Y.C. , Stein Anthony S. , Colcher David , Shively John E. , Yazaki Paul J. , Hui Susanta K.
Published: September 2019

Purpose:

Acute myeloid leukemia (AML) is a highly aggressive form of leukemia, which results in poor survival outcomes. Currently, diagnosis and prognosis are based on invasive single-point bone marrow biopsies (iliac crest). There is currently no AML-specific noninvasive imaging method to detect disease, including in extramedullary organs, representing an unmet clinical need. About 85% to 90% of human myeloid leukemia cells express CD33 cell surface receptors, highlighting CD33 as an ideal candidate for AML immunoPET.

Experimental Design:

We evaluated whether [64Cu]Cu-DOTA-anti-CD33 murine mAb can be used for immunoPET imaging of AML in a preclinical model. MicroCT was adjusted to detect spatial/anatomical details of PET activity. For translational purposes, a humanized anti-CD33 antibody was produced; we confirmed its ability to detect disease and its distribution. We reconfirmed/validated CD33 antibody-specific targeting with an antibody–drug conjugate (ADC) and radioimmunotherapy (RIT).

Results:

[64Cu]Cu-DOTA-anti-CD33–based PET-CT imaging detected CD33+ AML in mice with high sensitivity (95.65%) and specificity (100%). The CD33+ PET activity was significantly higher in specific skeletal niches [femur (P < 0.00001), tibia (P = 0.0001), humerus (P = 0.0014), and lumber spine (P < 0.00001)] in AML-bearing mice (over nonleukemic control mice). Interestingly, the hybrid PET-CT imaging showed high disease activity in the epiphysis/metaphysis of the femur, indicating regional spatial heterogeneity. Anti-CD33 therapy using newly developed humanized anti-CD33 mAb as an ADC (P = 0.02) and [225Ac]Ac-anti-CD33-RIT (P < 0.00001) significantly reduced disease burden over that of respective controls.

Conclusions:

We have successfully developed a novel anti-CD33 immunoPET-CT–based noninvasive modality for AML and its spatial distribution, indicating a preferential skeletal niche.
T-cell Receptors Engineered De Novo for Peptide Specificity Can Mediate Optimal T-cell Activity without Self Cross-Reactivity
Authors: Sharma Preeti , Harris Daniel T. , Stone Jennifer D. , Kranz David M.
Published: September 2019

Despite progress in adoptive T-cell therapies, the identification of targets remains a challenge. Although chimeric antigen receptors recognize cell-surface antigens, T-cell receptors (TCR) have the advantage that they can target the array of intracellular proteins by binding to peptides associated with major histocompatibility complex (MHC) products (pepMHC). Although hundreds of cancer-associated peptides have been reported, it remains difficult to identify effective TCRs against each pepMHC complex. Conventional approaches require isolation of antigen-specific CD8+ T cells, followed by TCRαβ gene isolation and validation. To bypass this process, we used directed evolution to engineer TCRs with desired peptide specificity. Here, we compared the activity and cross-reactivity of two affinity-matured TCRs (T1 and RD1) with distinct origins. T1-TCR was isolated from a melanoma-reactive T-cell line specific for MART-1/HLA-A2, whereas RD1-TCR was derived de novo against MART-1/HLA-A2 by in vitro engineering. Despite their distinct origins, both TCRs exhibited similar peptide fine specificities, focused on the center of the MART-1 peptide. In CD4+ T cells, both TCRs mediated activity against MART-1 presented by HLA-A2. However, in CD8+ T cells, T1, but not RD1, demonstrated cross-reactivity with endogenous peptide/HLA-A2 complexes. Based on the fine specificity of these and other MART-1 binding TCRs, we conducted bioinformatics scans to identify structurally similar self-peptides in the human proteome. We showed that the T1-TCR cross-reacted with many of these self-peptides, whereas the RD1-TCR was rarely cross-reactive. Thus, TCRs such as RD1, generated de novo against cancer antigens, can serve as an alternative to TCRs generated from T-cell clones.
Treatment of Social Anxiety Disorder and Avoidant Personality Disorder in Routine Care: A Naturalistic Study of Combined Individual and Group Therapy
Authors: Boettcher Johanna , Weinbrecht Anna , Heinrich Manuel , Renneberg Babette
Published: September 2019

Background: Cognitive behavioral therapy (CBT) in a group or individual format has proven effective for treating social anxiety in numerous randomized controlled trials. Studies in routine care are rare and focus exclusively on social anxiety disorder (SAD). Findings for avoidant personality disorder (AVPD) are missing. The current effectiveness study evaluates a combination of group and individual CBT for patients with SAD with or without AVPD. Methods: One hundred and five patients diagnosed with SAD with or without comorbid AVPD completed a combination of group and individual CBT. We administered outcome measures prior to individual therapy, prior to group therapy, after group therapy, and ­after individual therapy. Results: Patients experienced a strong decline in social anxiety symptoms (d = 1.1), depression (d = 1.0), and general mental distress (d = 1.1). They also showed a large increase in self-efficacy (d = 1.1). Descriptively, the largest decreases in social anxiety occurred during the group treatment. Controlling for pretreatment severity and depression, a comorbid diagnosis of AVPD was not associated with symptom improvement during treatment. Discussion: The results of the combined treatment were comparable to those of other effectiveness studies. Group treatment seemed to accelerate change in social fears. Patients with AVPD showed the same average improvements as patients without comorbid AVPD.
Neonatal Outcomes and Maternal Characteristics in Monochorionic Diamniotic Twin Pregnancies: Uncomplicated versus Twin-to-Twin Transfusion Syndrome Survivors after Fetoscopic Laser Surgery
Authors: Gheorghe Ciprian P. , Boring Noemi , Mann Lovepreet , Donepudi Roopali , Lopez Suzanne M. , Chauhan Suneet P. , Bhandari Vineet , Moise Jr. Kenneth J. , Johnson Anthony , Papanna Ramesha
Published: September 2019

Preterm birth remains a major complication of fetal laser surgery (FLS) due to twin-to-twin transfusion syndrome (TTTS). Objectives: We tested the hypothesis that neonatal outcomes in fetuses born at >24 weeks are worse in TTTS survivors compared to uncomplicated monochorionic diamniotic (MCDA) twins. Methods: 196 patients with TTTS treated with laser therapy and 91 uncomplicated MCDA gestations were compared. Neonatal outcomes included respiratory distress syndrome (RDS), transient tachypnea of the newborn (TTN), bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, and neonatal death. Risk factors assessed were TTTS, maternal age, maternal body mass index, race, premature prolonged rupture of membranes, stage of TTTS, parity, and gestational age (GA) at delivery. Results: GA at delivery was lower in the TTTS group (31.0 ± 4.6 vs. 33.5 ± 2.4 weeks, p < 0.001). RDS and TTN occurred at higher rates in the TTTS than in the uncomplicated MCDA group. After multivariate logistic regression, the only factor significantly associated with the composite adverse outcome was GA at delivery (OR 0.61; 95% CI: 0.58–0.7). Conclusion: TTTS twins treated with FLS are deliver 2.5 weeks earlier than uncomplicated MCDA twins. Respiratory complications were significantly higher in TTTS twins and were mainly the consequence of the early GA at delivery.