bluuebunny/crossref_metadata_2025 huggingface dataset:
OD
Authors: Campbell Nancy D.
Published: March 2020

The history of an unnatural disaster—drug overdose—and the emergence of naloxone as a social and technological solution.

For years, drug overdose was unmentionable in polite society. OD was understood to be something that took place in dark alleys—an ugly death awaiting social deviants—neither scientifically nor clinically interesting. But over the last several years, overdose prevention has become the unlikely object of a social movement, powered by the miracle drug naloxone. In OD, Nancy Campbell charts the emergence of naloxone as a technological fix for overdose and describes the remaking of overdose into an experience recognized as common, predictable, patterned—and, above all, preventable. Naloxone, which made resuscitation, rescue, and “reversal” after an overdose possible, became a tool for shifting law, policy, clinical medicine, and science toward harm reduction. Liberated from emergency room protocols and distributed in take-home kits to non-medical professionals, it also became a tool of empowerment.

After recounting the prehistory of naloxone—the early treatment of OD as a problem of poisoning, the development of nalorphine (naloxone's predecessor), the idea of “reanimatology”—Campbell describes how naloxone emerged as a tool of harm reduction. She reports on naloxone use in far-flung locations that include post-Thatcherite Britain, rural New Mexico, and cities and towns in Massachusetts. Drawing on interviews with approximately sixty advocates, drug users, former users, friends, families, witnesses, clinicians, and scientists—whom she calls the “protagonists” of her story—Campbell tells a story of saving lives amid the complex, difficult conditions of an unfolding unnatural disaster.
An atypical DYRK kinase connects quorum-sensing with posttranscriptional gene regulation in Trypanosoma brucei
Authors: Cayla Mathieu , McDonald Lindsay , MacGregor Paula , Matthews Keith
Published: March 2020

The sleeping sickness parasite, Trypanosoma brucei, uses quorum sensing (QS) to balance proliferation and transmission potential in the mammal bloodstream. A signal transduction cascade regulates this process, a component of which is a divergent member of the DYRK family of protein kinases, TbDYRK. Phylogenetic and mutational analysis in combination with activity and phenotypic assays revealed that TbDYRK exhibits a pre-activated conformation and an atypical HxY activation loop motif, unlike DYRK kinases in other eukaryotes. Phosphoproteomic comparison of TbDYRK null mutants with wild-type parasites identified molecules that operate on both the inhibitory ‘slender retainer’ and activatory ‘stumpy inducer’ arms of the QS control pathway. One of these molecules, the RNA-regulator TbZC3H20, regulates parasite QS, this being dependent on the integrity of its TbDYRK phosphorylation site. This analysis reveals fundamental differences to conventional DYRK family regulation and links trypanosome environmental sensing, signal transduction and developmental gene expression in a coherent pathway.
Cell-specific exon methylation and CTCF binding in neurons regulate calcium ion channel splicing and function
Authors: López Soto Eduardo Javier , Lipscombe Diane
Published: March 2020

Cell-specific alternative splicing modulates myriad cell functions and is disrupted in disease. The mechanisms governing alternative splicing are known for relatively few genes and typically focus on RNA splicing factors. In sensory neurons, cell-specific alternative splicing of the presynaptic CaV channel Cacna1b gene modulates opioid sensitivity. How this splicing is regulated is unknown. We find that cell and exon-specific DNA hypomethylation permits CTCF binding, the master regulator of mammalian chromatin structure, which, in turn, controls splicing in a DRG-derived cell line. In vivo, hypomethylation of an alternative exon specifically in nociceptors, likely permits CTCF binding and expression of CaV2.2 channel isoforms with increased opioid sensitivity in mice. Following nerve injury, exon methylation is increased, and splicing is disrupted. Our studies define the molecular mechanisms of cell-specific alternative splicing of a functionally validated exon in normal and disease states – and reveal a potential target for the treatment of chronic pain.
Cycloaddition Reactions of Alkene Radical Cations using Iron(III)‐Phenanthroline Complex
Authors: Cho Yong Hyun , Kim Jae Hyung , An Hyeju , Ahn Kwang‐Hyun , Kang Eun Joo
Published: March 2020

Single electron oxidation of electron‐rich alkenes using the iron(III)‐phenanthroline complex produced electrophilic alkene radical cations, which promoted efficient radical cation [2+1] cycloaddition reactions with diazo compounds. Subsequent chain propagation afforded tri‐ and tetra‐substituted cyclopropanes. This methodology was also expanded to [3+2] cycloaddition reactions with vinyl diazoesters, validating this sustainable, first‐row transition metal iron system for the single electron redox reactions.

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Synthesis of 1,4‐Benzothiazines via KI/DMSO/O2‐Mediated Three‐Component Oxidative Cyclization/Coupling
Authors: Zhao Jinwu , Luo Zhigao , Xu Jingxiu
Published: March 2020

A three‐component transition‐metal‐free aerobic method for the generation of 1,4‐benzothiazines is reported herein. The KI/DMSO/O2 system was found to be effective for the oxidative cyclization/coupling of 2‐aminobenzenethiols, anilines, and methylketones. Hence, various structurally important imino 1,4‐benzothiazines were assembled with broad functional group tolerance. Mechanistic studies revealed an initial oxidation of ketone α C−H bonds by the KI/DMSO/O2 oxidative system.

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Prognostic impact of p53 and/or NY‐ESO‐1 autoantibody induction in patients with gastroenterological cancers
Authors: Hoshino Isamu , Nabeya Yoshihiro , Takiguchi Nobuhiro , Gunji Hisashi , Ishige Fumitaka , Iwatate Yosuke , Shiratori Fumiaki , Yajima Satoshi , Okada Rei , Shimada Hideaki
Published: March 2020

Background and Aim

We evaluated the clinicopathological and prognostic significance of serum p53 (s‐p53‐Abs) and serum NY‐ESO‐1 autoantibodies (s‐NY‐ESO‐1‐Abs) in esophageal squamous cell carcinoma (ESCC), gastric cancer and hepatocellular carcinoma (HCC).

Patients and Methods

A total of 377 patients, 85 patients with ESCC, 248 patients with gastric cancer, and 44 patients with HCC were enrolled to measure s‐p53‐Abs and s‐NY‐ESO‐1‐Abs titers by the enzyme‐linked immunosorbent assay before treatment. The clinicopathological significance and prognostic impact of the presence of autoantibodies were evaluated. Expression data based on the Cancer Genome Atlas and the prognostic impact of gene expression was also examined for discussion.

Results

The positive rates of s‐p53‐Abs were 32.9% in ESCC, 15% in gastric cancer, and 4.5% in HCC. The positive rates of s‐NY‐ESO‐1‐Abs were 29.4% in ESCC, 9.7% in gastric cancer, and 13.6% in HCC. The presence of s‐p53‐Abs was not associated with tumor progression in these three cancer types. On the other hand, the presence of s‐NY‐ESO‐1‐Abs was significantly associated with tumor progression in ESCC and gastric cancer. The presence of s‐p53‐Abs and/or s‐NY‐ESO‐1‐Abs was significantly associated with poor prognosis in gastric cancer but not in ESCC nor HCC.

Conclusions

The presence of s‐p53‐Abs and/or s‐NY‐ESO‐1‐Abs was associated with tumor progression in ESCC and gastric cancer. These autoantibodies might have poor prognostic impacts on gastric cancer (UMIN000014530).
Quantitative distinction of thermodynamic soluble and miscible states
Authors: Zhang Kaiqiang , Jia Na , Liu Lirong
Published: March 2020

Soluble and miscible states are two important thermodynamic states in academic research and practical applications but their quantitative distinctions are still fuzzy. In this study, for the first time, the mathematical formulations of the quantitative criteria for distinguishing the thermodynamic soluble and miscible states are analytically developed by means of the Flory–Huggins solution theory and solubility parameter. The quantitative bottom and upper solubility limits for a total of 13 binary and ternary mixtures are calculated at different conditions. Moreover, the composition, temperature and pore radius are specifically studied to evaluate their effects on the soluble and miscible states. On the basis of the work from this study, the insoluble, soluble but immiscible, and miscible states are definitively quantified and clearly distinguished for the first time.
Health related quality of life varies by weight loss method in patients with history of nonalcoholic fatty liver disease
Authors: Bellavance Danielle , Halegoua‐Demarzio Dina
Published: March 2020

Weight loss through lifestyle modification is currently the standard of care in the management of patients with nonalcoholic fatty liver disease (NAFLD); however, benefits of specific strategies for achieving weight loss in these patients are poorly understood. We sought to determine whether patient satisfaction and health‐related quality of life (HRQoL) vary by specific weight loss method in patients with NAFLD. Patients diagnosed with NAFLD in the previous 6 months to 3 years were identified through chart review at our urban, tertiary medical center. Participants were administered an online questionnaire assessing liver disease and weight loss history, HRQoL, and satisfaction with their weight loss method. Patients who incorporated caloric restriction into their weight loss plans had lower total HRQoL scores (5.0 vs 5.4, P = .05) as compared to patients who did not include this method. Multivariate analysis showed that caloric restriction was independently associated with lower HRQoL scores (β = −2.25, P = .03). Weight loss was associated with both increased total HRQoL scores (5.3 vs 4.9, P = .05) and increased patient satisfaction scores (3.3 vs 2.1, P = 4.00 × 10−10). Our data demonstrate that incorporation of caloric restriction into a weight loss plan is associated with lower HRQoL. Choosing a weight loss strategy associated with improved quality of life could be an important factor in improving adherence and patient outcomes.
A Tale of Two Borders: Use‐Value Assessment, Land Development, and Irrigation Investment
Authors: Bigelow Daniel P. , Kuethe Todd
Published: March 2020

Since 1960, all 50 states in the US have adopted some form of preferential tax treatment for farmland. These provisions often take the form of use‐value assessment, where farmland is taxed on the basis of its value in agricultural production, as opposed to its full market value. While the main goal of use‐value assessment is to slow the conversion of farmland to non‐agricultural uses, other channels of influence are also possible, such as those stemming from reinvestment of foregone tax expenses. Despite its widespread nature, there is little empirical evidence pertaining to the influence of use‐value assessment on land‐use or investment decisions. Using a postmatching difference‐in‐differences framework, we exploit the temporal and spatial discontinuities surrounding the adoption of use‐value assessment in Kansas in 1989 to measure how use‐value assessment affected plot‐level land development and irrigation investment decisions. The results of our analysis indicate that, as intended, the use‐value assessment policy curtailed development in the Kansas City metropolitan area. Evidence regarding the potential investment‐spurring effects of use‐value assessment is more mixed, suggesting that farmers may have increased irrigation in some areas because of use‐value assessment‐induced tax savings.
Information and Communication Technologies to Provide Agricultural Advice to Smallholder Farmers: Experimental Evidence from Uganda
Authors: Van Campenhout Bjorn , Spielman David J. , Lecoutere Els
Published: March 2020

Agricultural advisory services generally rely on interpersonal knowledge transfers by agricultural extension agents who visit farmers to provide information. This approach is not always effective and has proved hard to scale sustainably, particularly in highly dispersed smallholder farming systems. Information and communication technologies (ICTs) have been advanced as a promising way to overcome many of the problems associated with conventional agricultural extension. We evaluate the effectiveness of an ICT‐mediated approach to deliver agricultural information in a field experiment conducted among small‐scale maize farmers in eastern Uganda. Three complementary technologies designed to address both informational and behavioral constraints to technical change are considered. First, we investigate the effectiveness of audiovisual messages (video) as a means of delivering information on input use and improved maize management practices to farmers. Second, we quantify the additional impact of complementing video with an interactive voice response (IVR) service. Third, we estimate the incremental effect of time‐sensitive short message services (SMS) messages designed to remind farmers about applying key practices at specific points during the season. We find that households that were shown a short video on how to become better maize farmers were performing significantly better on a knowledge test, more likely to apply recommended practices, and more likely to use fertilizer than households that did not view the video. These same households also reported maize yields about 10.5% higher than those that did not view the video. We find little evidence of an incremental effect of the IVR service or SMS reminders.
Synthese eines gegenanionstabilisierten Bis(silylium)ions
Authors: Wu Qian , Roy Avijit , Wang Guoqiang , Irran Elisabeth , Klare Hendrik F. T. , Oestreich Martin
Published: March 2020

Es wird über die Darstellung eines Moleküls mit zwei alkylverknüpften Silyliumionzentren ausgehend vom entsprechenden Bis(hydrosilan) mittels zweifacher Hydridabstraktion berichtet. Die Länge der konformativ flexiblen Alkylbrücke ist entscheidend, denn sonst bleibt die Hydridabstraktion auf der Stufe eines cyclischen bissilylierten Hydroniumions stehen. Für den Fall einer Ethylenbrücke ist die offene Form der Hydroniumionzwischenstufe energetisch zugänglich und geht eine weitere Hydridabstraktion ein. Das daraus hervorgehende Bis(silylium)ion wurde NMR‐spektroskopisch und strukturell charakterisiert. Verwandte Systeme auf der Grundlage von starren Naphthalen‐n,m‐diylplattformen können nur dann in die Dikationen überführt werden, wenn die positiv geladenen Silyliumioneinheiten voneinander entfernt sind (1,8 gegenüber 1,5 und 2,6).
Preparation of Functionalized Aryl, Heteroaryl, and Benzylic Potassium Organometallics Using Potassium Diisopropylamide in Continuous Flow
Authors: Harenberg Johannes H. , Weidmann Niels , Knochel Paul
Published: March 2020

We report the preparation of lithium‐salt‐free KDA (potassium diisopropylamide; 0.6 m in hexane) complexed with TMEDA (N,N,N′,N′‐tetramethylethylenediamine) and its use for the flow‐metalation of (hetero)arenes between −78 °C and 25 °C with reaction times between 0.2 s and 24 s and a combined flow rate of 10 mL min−1 using a commercial flow setup. The resulting potassium organometallics react instantaneously with various electrophiles, such as ketones, aldehydes, alkyl and allylic halides, disulfides, Weinreb amides, and Me3SiCl, affording functionalized (hetero)arenes in high yields. This flow procedure is successfully extended to the lateral metalation of methyl‐substituted arenes and heteroaromatics, resulting in the formation of various benzylic potassium organometallics. A metalation scale‐up was possible without further optimization.
Position and feedback for digital microfluidic system based on light intensity information
Authors: Luo Zhijie , Fan Junjun , Huang Bangrui , Liu Shuangyin , Dai Feng
Published: March 2020

The digital microfluidic system based on electrowetting on dielectric is a new technology that can control microliter droplets within the plane. Because of layout, fabrication, and driving uncertainties, feedback control schemes must be designed and implemented to ensure safety and reliability of digital microfluidic system for practical application. The basis for feedback is to realize the accurate droplet location. So, there is a strong need for the development of a digital microfluidic system integrated with position and feedback scheme for innovative biological research. In this paper, we propose a position and feedback scheme based on light intensity for digital microfluidic system. The verified experiment results show that the proposed position and feedback scheme can position multiple droplets accurately and improve the success rate of droplets transport application by feedback.
Cultural determinants in Winnicott's developmental theories
Authors: Dajani Karim G.
Published: March 2020

This article applies a cultural or collective perspective to Winnicott's developmental theories. Expanding on existing psychoanalytic literature and drawing from neighboring fields, specifically the work of the French sociologist and anthropologist Pierre Bourdieu, the notion of habitus is utilized to account for the constitutive impact of culture or a collective on individual development. Cultural systems play a fundamental role in the structuring of subjectivity and the coordination of inter‐subjective linking. Collective systems of meaning‐making (cultures) replicate themselves in the minds of individuals who are structured by them. Extending this idea to Winnicott's developmental theories will help illuminate the constitutive impact of Winnicott's cultures or collectives on his perception, thinking and theories. A case example illustrating the thesis of cultures’ constitutive impact on an individual's basic experience of self and world is provided.
Synergistic Assembly of a CoS@NiFe/Ni Foam Heterostructure Electrocatalyst for Efficient Water Oxidation Catalysis at Large Current Densities
Authors: Wang Muheng , Wu Yun , Li Na , Zhao Fei , Zhao Qiang , Li Jinping , Liu Guang
Published: March 2020

Electrochemical water splitting is an ideal pollution‐free path to generate hydrogen at large scale, however, the development of highly catalytic electrocatalysts for the water oxidation reaction at large current densities is still a fundamental challenge. Herein, we report a novel, high‐wettability water‐oxidation electrocatalyst composed of an amorphous NiFe layer and CoS film on commercial nickel foam via a two‐step electrodeposition synthetic path. Benefiting from the strong interactions between the NiFe layer and CoS film, enlarged surface active sites and enhanced wettability, the CoS@NiFe/NF electrode exhibited an outstanding water oxidation performance at 10 mA/cm2 with an overpotential of 175 mV in 1 M KOH solution and steadily delivered a current density of 1 A/cm2 at merely 330 mV in 30 wt% KOH solution. Even at large densities, the CoS@NiFe/NF hybrids also showed excellent water oxidation stability and corrosion resistance for at least 24 h. Such a synergistic assembling approach to fabricate a CoS@NiFe/NF heterostructure together with excellent OER performance may be a promising strategy for rationally building and designing heterostructural electrocatalysts towards highly efficient water oxidation reaction.
meso‐Free BIII Subporphyrins with Electron‐donating Groups
Authors: Bekki Yosuke , Osuka Atsuhiro
Published: March 2020

meso‐Free BIII 5,10‐bis(p‐dimethylaminophenyl)subporphyrins were synthesized. They display red‐shifted absorption and fluorescence spectra, bathochromic behaviors in polar solvents, a high fluorescence quantum yield (ΦF=0.57), and a small HOMO–LUMO gap mainly due to destabilized HOMO as compared with meso‐free BIII 5,10‐diphenylsubporphyrin. This subporphyrin serves as a nice precursor of various meso‐substituted BIII subporphyrins such as BIII meso‐nitrosubporphyrin, BIII meso‐aminosubporphyrin, and meso‐meso’ linked BIII azosubporphyrin dimer. Reactions of meso‐free BIII subporphyrins with NBS or bis(2,4,6‐trimethylpyridine)bromonium hexafluorophosphate gave meso‐meso′ linked subporphyrin dimers, often as a major product along with meso‐bromosubporphyrins.
Lost in translation: “Risks,” “needs,” and “evidence” in implementing the First Step Act
Authors: Skeem Jennifer , Monahan John
Published: March 2020

In this article, we focus on two highly problematic issues in the manner in which the First Step Act of 2018 is being implemented by the Bureau of Prisons: an uncritical separation of “dynamic risks” and “criminogenic needs”; and a spurious reliance on “evidence‐based” interventions to reduce recidivism risk. We argue that if the Act is to live up to its promise of being a game‐changing development in efforts to reduce crime while simultaneously shrinking mass incarceration, “needs assessment” must be subject to vastly increased empirical attention, variable and causal risk factors must be identified and validly assessed, and interventions to reduce risk must be rigorously evaluated both for their fidelity of implementation and impact on recidivism. Rather than further proliferating programs that ostensibly reduce risk, we believe that serious consideration should be given to the Bureau of Prisons offering one signature, well‐established cognitive‐behavioral program that can simultaneously address multiple risk factors for moderate and high‐risk prisoners.
Long‐term results of vascularized proximal fibula epiphyseal transfer based on the anterior tibial artery in retrograde fashion
Authors: Ishiura Ryohei , Sawaizumi Masayuki
Published: March 2020

Injury of bone growth plates can result in severe disability in children. We report the long‐term results of successful vascularized proximal fibula epiphyseal transfer based on the anterior tibial artery in retrograde fashion.
Distannabarrelenes with Three Coordinated SnII Atoms
Authors: Sharma Mahendra K. , Glodde Timo , Neumann Beate , Stammler Hans‐Georg , Ghadwal Rajendra S.
Published: March 2020

Crystalline 1,4‐distannabarrelene compounds [(ADCAr)3Sn2]SnCl3 (3‐Ar) (ADCAr={ArC(NDipp)2CC}; Dipp=2,6‐iPr2C6H3, Ar=Ph or DMP; DMP=4‐Me2NC6H4) derived from anionic dicarbenes Li(ADCAr) (2‐Ar) (Ar=Ph or DMP) have been reported. The cationic moiety of 3‐Ar features a barrelene framework with three coordinated SnII atoms at the 1,4‐positions, whereas the anionic unit SnCl3 is formally derived from SnCl2 and chloride ion. The all carbon substituted bis‐stannylenes 3‐Ar have been characterized by NMR spectroscopy and X‐ray diffraction. DFT calculations reveal that the HOMO of 3‐Ph (ϵ=−6.40 eV) is mainly the lone‐pair orbital at the SnII atoms of the barrelene unit. 3‐Ar readily react with sulfur and selenium to afford the mixed‐valence SnII/SnIV compounds [(ADCAr)3SnSn(E)](SnCl6)0.5 (E=S 4‐Ar, Ar=Ph or DMP; E=Se 5‐Ph).
Ruthenium‐Catalyzed Site‐Selective Trifluoromethylations and (Per)Fluoroalkylations of Anilines and Indoles
Authors: Li Yang , Neumann Helfried , Beller Matthias
Published: March 2020

Introducing (per)fluoroalkyl groups into arenes continues to be an interesting, but challenging area in organofluorine chemistry. We herein report an ortho‐selective C−H perfluoroalkylation including trifluoromethylations of anilines and indoles without the need of protecting groups using RfI and RfBr as commercially available reagents. The availability and price of the starting materials and the inherent selectivity make this novel methodology attractive for the synthesis of diverse (per)fluoroalkylated building blocks, for example, for bioactive compounds and materials.
RhodiumIII/SilverI Relay Catalyzed C—H Aminomethylation with Imine Equivalents and Lewis Acid Catalyzed [4+2] Cycloaddition of Indoles with Triarylhexahydrotriazine†
Authors: Liu Ruixing , Wei Yin , Shi Min
Published: March 2020

Summary of main observation and conclusion

A RhIII/AgI relay‐catalyzed C(sp2)—H coupling of indoles with triarylhexahydrotriazine (THT) is reported in this context. Upon merging RhIII‐catalyzed C(sp2)—H bond activation and silver promoted THT dissociation, an efficient indole's C3 aminomethylation protocol is uncovered, providing C3 aminomethyl indoles in good yields and exhibiting potential applications for the synthesis of complicated bioactive compounds. We revealed the C3‐selectivity of this reaction through a detailed mechanistic investigation. Meanwhile, during the examination of the reaction conditions, we discovered another [4+2] cycloaddition pathway to afford tetrahydro‐indolo[3,2‐c]quinoline scaffold products via silver or Lewis acid catalysis.
On authenticated skyline query processing over road networks
Authors: Zhu Xiaoyu , Wu Jie , Chang Wei , Zakirul Alam Bhuiyan Md , Raymond Choo Kim‐Kwang , Qi Fang , Liu Qin , Wang Guojun
Published: March 2020

In recent times, many location‐based service providers (LBSPs) choose to outsource data query services to third‐party cloud service providers (CSPs). This allows users to easily search for points of interests (POIs), such as restaurants and parking lots in their vicinity, using their mobile devices and in‐vehicle infotainment units. Skyline query is one potential technique to be deployed for road networks. However, the untrusted CSPs may forge or omit query results, intentionally or not. Therefore, in this article, we posit that by observing the unique properties of skyline query results in road networks, we can bind each POI with four nearby POIs with special properties using signature chain technology. Our proposed approach not only provides users with skyline query result authentication ability over the road network, but also have low communication overhead. Specifically, the overhead analysis and experimental results show that our proposed approach decreases the communication overhead.
Evolutionary gaming approach for decision making of Tier‐3 Internet service provider networks migration to SoDIP6 networks
Authors: Dawadi Babu R. , Rawat Danda B. , Joshi Shashidhar R. , Manzoni Pietro
Published: March 2020

With the increasing number of Internet of Things (IoT) devices, current networking world is suffering in terms of management and operations with lack of IPv4 addresses leading to issues like network address translation (NAT) proliferation, security and quality of services. Software‐defined networking (SDN) and Internet Protocol version 6 (IPv6) are the new networking paradigms evolved to address related issues of legacy IPv4 networking. To adapt with global competitive environment and avoid all existing issues in legacy networking system, network service providers have to migrate their networks into IPv6 and SDN‐enabled networks. But immediate transformations of existing network are not viable due to several factors like higher cost of migration, lack of technical human resources, lack of standards and protocols during transitions, and many more. In this paper, we present the migration analysis for proper decision making of network transition in terms of customer demand, traffic engineering, and organizational strength with operation expenditure for network migration using evolutionary gaming approach. Joint migration to SDN‐enabled IPv6 network from game theoretic perspective is modeled and is validated using numerical results obtained from simulations. Our empirical analysis shows the evolutionary process of network migration while different internal and external factors in the organization affect the overall migration. Evolutionary game in migration planning is supportive in decision making for service providers to develop suitable strategy for their network migration. The proposed approach for migration decision making is mostly applicable to fairly sustained service providers who lack economics, regulation/policy, and resources strengths.
Low doses of recombinant human erythropoietin does not affect C‐terminal FGF23 in healthy men
Authors: Bejder Jacob , Robach Paul , Lundby Anne‐Kristine , Cornu Catherine , Sallet Pierre , Cairo Gaetano , Lundby Carsten
Published: March 2020

Recombinant human erythropoietin (rhEpo) can improve human performance, but misuse remains difficult to detect. C‐terminal fibroblast growth factor 23 (cFGF23) was recently demonstrated to increase following injection of a single high dose rhEpo, but the effect of more frequent low doses is unknown. Using a randomized double‐blind placebo‐controlled design, we investigated whether 2 weeks of subcutaneous injections three times a week of 50 IU/kg Eprex (low‐dose) or 20 IU/kg Eprex (micro‐dose) increase cFGF23 levels compared with saline (placebo) injections in 24 healthy males. Venous blood was sampled at day −3, 0, 1, 3, 11, 14, 18, and 25 of the treatment and analyzed for cFGF23 and erythropoietin concentration ([EPO]). The level of cFGF23 was similar at days −3, 0, 1, 3, 11, 14, 18, and 25 with the low‐dose (23 ± 4, 26 ± 5, 23 ± 7, 27 ± 6, 25 ± 8, 24 ± 10, 22 ± 5, and 24 ± 7 RU/mL, respectively), micro‐dose (23 ± 6, 25 ± 5, 23 ± 8, 28 ± 9, 27 ± 7, 25 ± 9, 25 ± 5, and 23 ± 6 RU/mL, respectively) and placebo (23 ± 6, 24 ± 6, 26 ± 7, 26 ± 6, 31 ± 6, 31 ± 7, 24 ± 4, and 27 ± 8 RU/mL, respectively) treatment. The correlation coefficient between plasma [EPO] and plasma cFGF23 levels was R2 = 0.01 and insignificant. The results demonstrate that cFGF23 is not sensitive to low doses of subcutaneous rhEpo injections in healthy males.
Heart failure treatment up‐titration and outcome and age: an analysis of BIOSTAT‐CHF
Authors: Mordi Ify R. , Ouwerkerk Wouter , Anker Stefan D. , Cleland John G. , Dickstein Kenneth , Metra Marco , Ng Leong L. , Samani Nilesh J. , van Veldhuisen Dirk J. , Zannad Faiez , Voors Adriaan A. , Lang Chim C.
Published: March 2020

Aims

Several studies have shown that older patients with heart failure with reduced ejection fraction (HFrEF) are undertreated. The aim of this study was to evaluate the association of up‐titration of angiotensin‐converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB) and beta‐blockers on outcome across the age spectrum in HFrEF patients.

Methods and results

We analysed HFrEF patients on sub‐optimal doses of ACEI/ARB and/or beta‐blockers from the BIOSTAT‐CHF study stratified by age. Patients underwent a 3‐month up‐titration period. We used inverse probability weighting to adjust for the likelihood of successful up‐titration to determine the association of achieved dose with mortality and/or heart failure hospitalisation, testing for an interaction with age. Over a median follow‐up of 21 months in 1720 HFrEF patients (76.5% male, mean age 67 years), the primary outcome occurred in 558 patients. Increased percentage of target dose of ACEI/ARB and beta‐blocker achieved at 3 months were both significantly associated with reduced incidence of the primary outcome, [ACEI‐ARB: hazard ratio (HR) per 12.5% increase in dose: 0.92, 95% confidence interval (CI) 0.91–0.94, P < 0.001; beta‐blocker: HR 0.98, 95% CI 0.95–1.00, P = 0.046], with a significant interaction with age seen for beta‐blockers but not ACEI/ARB (P = 0.034 and P = 0.22, respectively).

Conclusions

Achieving higher doses of ACEI/ARB was associated with improved outcome regardless of age. However, achieving higher doses of beta‐blockers was only associated with improved outcome in younger, but not in older patients.
Financial distress prediction model: The effects of corporate governance indicators
Authors: Chen Chih‐Chun , Chen Chun‐Da , Lien Donald
Published: March 2020

This paper constructs a financial distress prediction model that includes not only traditional financial variables, but also several important corporate governance variables. Using data from Taiwan, the empirical results show that the best in‐sample and out‐of‐sample prediction models should combine the financial variables with the corporate governance variables. Moreover, the prediction accuracy is higher for the models using dynamic distress threshold values than those with tradition threshold values. Most financial ratios, except for the debt ratio, are higher in financially sound companies than in financial distressed ones. With regard to the corporate governance variables, we find that the CEO/Chairman duality may not result in the outbreak of financial distress, but higher equity pledge ratios of managers (shareholding ratios by board members and insiders) positively (negatively) correlate with financial distress.
Empirical assessment of changing sample‐characteristics in task‐fMRI over two decades: An example from gustatory and food studies
Authors: Yeung Andy W. K. , Wong Natalie S. M. , Eickhoff Simon B.
Published: March 2020

Over the past two decades, functional neuroimaging has not only grown into a large field of research, but also substantially evolved. Here we provide a quantitative assessment of these presumed in sample composition and data analysis, using fMRI studies on food/taste research published between 1998 and 2019 as an exemplary case in which the scientific objectives themselves have remained largely stable. A systematic search for papers written in English was done using multiple databases and identified 426 original articles that were subsequently analyzed. The median sample size significantly increased from 11.5 to 35.5 while the ratio of male to female subjects remained stable. There were, however, more papers involving female subjects only, rather than male subjects only, since 2003. There was a decline in uncorrected results and statistical correction by false‐discovery rate. Reflecting a trend toward more conservative thresholding, the number of foci reported per paper did not change significantly and sample size (power) did not correlate with the number of reported foci. The median journal impact factor and the normalized number of citations (citations per year) of the papers, in turn, showed a significantly decreasing trend. Number of citations negatively correlated to sample size, publication year but positively correlated to journal impact factor, and was also influenced by statistical correction method. There was a decreasing trend in studies recruiting both left‐handed and right‐handed subjects. In summary, the present paper quantifies several large‐scale trends that have often been anecdotally discussed and reveals the changing nature of neuroimaging studies that may be considered when pursuing meta‐analytic approaches.
High Protein Intake Is Associated With Histological Disease Activity in Patients With NAFLD
Authors: Lang Sonja , Martin Anna , Farowski Fedja , Wisplinghoff Hilmar , Vehreschild Maria J.G.T. , Liu Jinyuan , Krawczyk Marcin , Nowag Angela , Kretzschmar Anne , Herweg Jens , Schnabl Bernd , Tu Xin M. , Lammert Frank , Goeser Tobias , Tacke Frank , Heinzer Kathrin , Kasper Philipp , Steffen Hans‐Michael , Demir Münevver
Published: March 2020

Overconsumption of carbohydrates and lipids are well known to cause nonalcoholic fatty liver disease (NAFLD), while the role of nutritional protein intake is less clear. In Western diet, meat and other animal products are the main protein source, with varying concentrations of specific amino acids. Whether the amount or composition of protein intake is associated with a higher risk for disease severity has not yet been examined. In this study, we investigated associations of dietary components with histological disease activity by analyzing detailed 14‐day food records in a cohort of 61 patients with biopsy‐proven NAFLD. Furthermore, we used 16S ribosomal RNA gene sequencing to detect associations with different abundances of the gut microbiota with dietary patterns. Patients with definite nonalcoholic steatohepatitis (NAFLD activity score of 5‐8 on liver biopsy) had a significantly higher daily relative intake of protein compared with patients with a NAFLD activity score of 0‐4 (18.0% vs. 15.8% of daily protein‐based calories, P = 0.018). After adjustment for several potentially confounding factors, a higher protein intake (≥17.3% of daily protein‐based calories) remained associated with definite nonalcoholic steatohepatitis, with an odds ratio of 5.09 (95% confidence interval 1.22‐21.25, P = 0.026). This association was driven primarily by serine, glycine, arginine, proline, phenylalanine, and methionine. A higher protein intake correlated with a lower Bacteroides abundance and an altered abundance of several other bacterial taxa. Conclusion: A high protein intake was independently associated with more active and severe histological disease activity in patients with NAFLD. Further studies are needed to investigate the potential harmful role of dietary amino acids on NAFLD, with special attention to meat as their major source.
Brain tumor segmentation and classification via adaptive CLFAHE with hybrid classification
Authors: Leena Bojaraj , Jayanthi Annamalai
Published: March 2020

This article exploits a new brain tumor classification model that includes five steps like (a) denoising, (b) skull stripping, (c) segmentation, (d) feature extraction and (e) classification. Initially, the image is subjected under the denoising process, where the noise removal procedure is carried out by employing the entropy‐based trilateral filter. Then, the denoised image is applied to the skull stripping process via Otsu thresholding and morphology segmentation. Subsequently, the next step is the segmentation, where the image is segmented by deploying the adaptive CLFAHE (contrast limited fuzzy adaptive histogram equalization) technique. Once the segmentation is completed, gray‐level co‐occurrence matrix (GLCM) based features are extracted. Finally, the extracted features are processed under hybrid classification model to attain enhanced classification rate. Here, hybrid classification hybrids two classifiers namely deep belief network (DBN) and Bayesian regularization classifier. The vital contribution of this research work exists in the optimal selection of hidden neurons in the DBN. Along with this, the membership function (bounding limits) of fuzzy logic is optimally selected. For this, a new lion exploration based whale optimization (LE‐WO) algorithm is proposed in this article that hybrids the concept of (lion algorithm) LA and (whale optimization algorithm) WOA. Finally, the performance of proposed LE‐WO is compared over the other methods in terms of accuracy, sensitivity, specificity, precision, negative predictive value (NPV), F1_score and Matthews correlation coefficient (MCC), False positive rate (FPR), False negative rate (FNR) and false discovery rate (FDR) and proves the betterments of proposed work. From the outcomes, the accuracy measure of proposed model at 60th population size is 1.98%, 1.81%, 1.32%, 3.46% and 0.75% better than PSO, FF, GWO, WOA and LA, respectively. Similarly, in 80th population size, the performance of the implemented model is 4.47%, 5.04%, 3.96%, 6.29% and 1.37% superior to PSO, FF, GWO, WOA and LA, respectively. Thus, the betterment of the adopted scheme is validated in an effective manner.
Mammographic mass segmentation using multichannel and multiscale fully convolutional networks
Authors: Xu Shengzhou , Adeli Ehsan , Cheng Jie‐Zhi , Xiang Lei , Li Yang , Lee Seong‐Whan , Shen Dinggang
Published: March 2020

Breast cancer is one of the leading causes of death among women worldwide. Mammographic mass segmentation is an important task in mammogram analysis. This process, however, poses a prominent challenge considering that masses can be obscured in images and appear with irregular shapes and low image contrast. In this study, a multichannel, multiscale fully convolutional network is proposed and evaluated for mass segmentation in mammograms. To reduce the impact of surrounding unrelated structures, preprocessed images with a salient mass appearance are obtained as the second input channel of the network. Furthermore, to jointly conduct fine boundary delineation and global mass localization, we incorporate more crucial context information by learning multiscale features from different resolution levels. The performance of our segmentation approach is compared with that of several traditional and deep‐learning‐based methods on the popular DDSM and INbreast datasets. The evaluation indices consist of the Dice similarity coefficient, area overlap measure, area undersegmentation measure, area oversegmentation measure, and Hausdorff distance. The mean values of the Dice similarity coefficient and Hausdorff distance of our proposed segmentation method are 0.915 ± 0.031 and 6.257 ± 3.380, respectively, on DDSM and 0.918 ± 0.038 and 2.572 ± 0.956, respectively, on INbreast, which are superior to those of the existing methods. The experimental results verify that our proposed multichannel, multiscale fully convolutional network can reliably segment masses in mammograms.
Breast cancer‐derived exosomes: Tumor progression and therapeutic agents
Authors: Jabbari Nasrollah , Akbariazar Elinaz , Feqhhi Maryam , Rahbarghazi Reza , Rezaie Jafar
Published: March 2020

Tumor cells secrete extracellular vesicles (EVs) for intercellular communication. EVs by transporting different proteins, nucleic acids, and lipids contribute to affect target cell function and fate. ‎EVs which originate directly from multivesicular bodies so‐called exosomes have dramatically fascinated the attention of researchers owing to their ‎pivotal roles in the tumorigenesis. Breast cancer, arising from milk‐producing cells, is the most identified cancer among women and has become the leading cause of cancer‐related death in women globally. Although different therapies are applied to eliminate breast tumor cells, however, the efficient therapy and survival rate of patients remain challenges. Growing evidence ‎shows exosomes from breast cancer cells contribute to proliferation, metastasis, angiogenesis, chemoresistance, and also radioresistance and, thus carcinogenesis. Additionally, these exosomes may serve as a cancer treatment tool because they are a good candidate for cancer diagnosis (as biomarker) and therapy (as drug‐carrier). Despite recent development in the biology of tumor‐derived exosomes, the detailed mechanism of tumorigenesis, and exosome‐based cancer‐therapy remain still indefinable. Here, we discuss the key function of breast cancer‐derived exosomes in tumorgenesis and shed light on the possible clinical application of these exosomes in breast cancer treatment.
Distinguishing gastroesophageal reflux disease and eosinophilic esophagitis in adults: The role of esophageal mucosal immunoglobulin G4
Authors: Wong Stephanie , Smith Georgia , Ruszkiewicz Andrew , Nguyen Nam Q
Published: March 2020

Background and Aim

Eosinophilic esophagitis (EoE) and gastroesophageal reflux disease (GERD) can be difficult to distinguish as many of their clinical and histological features overlap. Preliminary data suggest a potential association between EoE and immunoglobulin G4 (IgG4) but not GERD. This study aimed to examine the role of esophageal mucosal IgG4 staining when differentiating EoE from GERD.

Methods

Esophageal biopsy specimens from patients with proven EoE and GERD were evaluated, and immunohistochemical staining for IgG4 was performed by an experienced gastrointestinal pathologist blinded to the clinical and endoscopic data. The results on IgG4 staining were then correlated with clinical, endoscopic, and histological features.

Results

Sixty patients were included in the study, with 30 EoE (38.8 ± 12.8 years, 23 M:7 F) and 30 GERD (50.7 ± 14.3 years, 14 M:16 F) patients. The prevalence of a positive intercellular IgG4 stain was significantly higher in the EoE patients than those with GERD (23/29 vs 2/30; P < 0.0001). Positive IgG4 stain had the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 77%, 93%, 92%, and 80% for predicting the diagnosis of EoE, respectively. In both EoE and GERD patients, correlation was found between positive IgG4 staining and food bolus obstruction, dysphagia to solids, reflux, fixed rings, Barrett's esophagus, hiatus hernia, and esophagitis. In EoE patients, positive IgG4 staining was not correlated with the type of symptoms, endoscopic findings, histological findings, proton pump inhibitor therapy, or history of allergy/atopy.

Conclusion

Given the high specificity and PPV of positive IgG4 staining in esophageal biopsies for EoE, this can be a useful marker to distinguish the disease from GERD.
Severe phenotype of ATP6AP1‐CDG in two siblings with a novel mutation leading to a differential tissue‐specific ATP6AP1 protein pattern, cellular oxidative stress and hepatic copper accumulation
Authors: Ondruskova Nina , Honzik Tomas , Vondrackova Alzbeta , Stranecky Viktor , Tesarova Marketa , Zeman Jiri , Hansikova Hana
Published: March 2020

Congenital disorders of glycosylation (CDG) represent a wide range of >140 inherited metabolic diseases, continually expanding not only with regards to the number of newly identified causative genes, but also the heterogeneity of the clinical and molecular presentations within each subtype. The deficiency of ATP6AP1, an accessory subunit of the vacuolar H+‐ATPase, is a recently characterised N‐ and O‐glycosylation defect manifesting with immunodeficiency, hepatopathy and cognitive impairment. At the cellular level, the latest studies demonstrate a complex disturbance of metabolomics involving peroxisomal function and lipid homeostasis in the patients. Our study delineates a case of two severely affected siblings with a new hemizygous variant c.221T>C (p.L74P) in ATP6AP1 gene, who both died due to liver failure before reaching 1 year of age. We bring novel pathobiochemical observations including the finding of increased reactive oxygen species in the cultured fibroblasts from the older boy, a striking copper accumulation in his liver, as well as describe the impact of the mutation on the protein in different organs, showing a tissue‐specific pattern of ATP6AP1 level and its posttranslational modification.
Liver ultrasound: A key procedure in the surgeon's toolbox
Authors: Hagopian Ellen J.
Published: March 2020

Intraoperative liver ultrasound (US) is an imperative adjunctive procedure during any liver surgical procedure. Intraoperative US can be used to confirm preoperative findings, to identify new findings, and to guide the conduct of the procedure. A major barrier to incorporation of US into the surgeon's toolbox is training and education. A standardized training program for surgical fellows has been developed based on the mastery learning framework.
Injustice is Served: Injustice Mediates the Effects of Interpersonal Physical Trauma on Posttraumatic Stress Symptoms and Depression Following Traumatic Injury
Authors: Boals Adriel , Trost Zina , Warren Ann Marie , McShan Evan E.
Published: March 2020

Previous research has consistently found that traumas of an interpersonal nature are associated with elevated levels of posttraumatic stress symptoms (PTSS). In the current study, we examined whether feelings of injustice related to sustained physical trauma mediate the association between the interpersonal nature of a traumatic injury and two outcomes: PTSS and depressive symptoms. The sample consisted of 176 patients admitted to a Level 1 trauma center for traumatic injuries. Participants completed measures of PTSS, depressive symptoms, and injury‐related injustice perception at baseline and again at 3‐ and 6‐month postinjury follow‐ups. The results revealed that, compared to noninterpersonal injuries, interpersonal injuries were related to significantly higher levels of perceived injustice, PTSS, and depressive symptoms at all three assessment points, except for PTSS at baseline, ds = 0.47–1.23. These associations remained significant after accounting for injury severity. It is important to note that higher levels of perceived injustice 3‐month postinjury follow‐up mediated the association between the interpersonal nature of the trauma and higher levels of PTSS and depressive symptoms at 6 months postinjury. Our results suggest injustice may be an important factor that helps explain why interpersonal traumas are associated with poorer mental health outcomes than noninterpersonal traumas. Additionally, the current study provides some of the first prospective analyses of injustice perception and trauma outcomes.