bluuebunny/crossref_metadata_2025 huggingface dataset:
SARM1 acts downstream of neuroinflammatory and necroptotic signaling to induce axon degeneration
Authors: Ko Kwang Woo , Milbrandt Jeffrey , DiAntonio Aaron
Published: July 2020

Neuroinflammation and necroptosis are major contributors to neurodegenerative disease, and axon dysfunction and degeneration is often an initiating event. SARM1 is the central executioner of pathological axon degeneration. Here, we demonstrate functional and mechanistic links among these three pro-degenerative processes. In a neuroinflammatory model of glaucoma, TNF-α induces SARM1-dependent axon degeneration, oligodendrocyte loss, and subsequent retinal ganglion cell death. TNF-α also triggers SARM1-dependent axon degeneration in sensory neurons via a noncanonical necroptotic signaling mechanism. MLKL is the final executioner of canonical necroptosis; however, in axonal necroptosis, MLKL does not directly trigger degeneration. Instead, MLKL induces loss of the axon survival factors NMNAT2 and STMN2 to activate SARM1 NADase activity, which leads to calcium influx and axon degeneration. Hence, these findings define a specialized form of axonal necroptosis. The demonstration that neuroinflammatory signals and necroptosis can act locally in the axon to stimulate SARM1-dependent axon degeneration identifies a therapeutically targetable mechanism by which neuroinflammation can stimulate axon loss in neurodegenerative disease.
Topological features of integrin adhesion complexes revealed by multiplexed proximity biotinylation
Authors: Chastney Megan R. , Lawless Craig , Humphries Jonathan D. , Warwood Stacey , Jones Matthew C. , Knight David , Jorgensen Claus , Humphries Martin J.
Published: July 2020

Integrin adhesion complexes (IACs) bridge the extracellular matrix to the actin cytoskeleton and transduce signals in response to both chemical and mechanical cues. The composition, interactions, stoichiometry, and topological organization of proteins within IACs are not fully understood. To address this gap, we used multiplexed proximity biotinylation (BioID) to generate an in situ, proximity-dependent adhesome in mouse pancreatic fibroblasts. Integration of the interactomes of 16 IAC-associated baits revealed a network of 147 proteins with 361 proximity interactions. Candidates with underappreciated roles in adhesion were identified, in addition to established IAC components. Bioinformatic analysis revealed five clusters of IAC baits that link to common groups of prey, and which therefore may represent functional modules. The five clusters, and their spatial associations, are consistent with current models of IAC interaction networks and stratification. This study provides a resource to examine proximal relationships within IACs at a global level.
Protrudin-mediated ER–endosome contact sites promote MT1-MMP exocytosis and cell invasion
Authors: Pedersen Nina Marie , Wenzel Eva Maria , Wang Ling , Antoine Sandra , Chavrier Philippe , Stenmark Harald , Raiborg Camilla
Published: July 2020

Cancer cells break tissue barriers by use of small actin-rich membrane protrusions called invadopodia. Complete invadopodia maturation depends on protrusion outgrowth and the targeted delivery of the matrix metalloproteinase MT1-MMP via endosomal transport by mechanisms that are not known. Here, we show that the ER protein Protrudin orchestrates invadopodia maturation and function. Protrudin formed contact sites with MT1-MMP–positive endosomes that contained the RAB7-binding Kinesin-1 adaptor FYCO1, and depletion of RAB7, FYCO1, or Protrudin inhibited MT1-MMP–dependent extracellular matrix degradation and cancer cell invasion by preventing anterograde translocation and exocytosis of MT1-MMP. Moreover, when endosome translocation or exocytosis was inhibited by depletion of Protrudin or Synaptotagmin VII, respectively, invadopodia were unable to expand and elongate. Conversely, when Protrudin was overexpressed, noncancerous cells developed prominent invadopodia-like protrusions and showed increased matrix degradation and invasion. Thus, Protrudin-mediated ER–endosome contact sites promote cell invasion by facilitating translocation of MT1-MMP–laden endosomes to the plasma membrane, enabling both invadopodia outgrowth and MT1-MMP exocytosis.
Rashomon at the kinetochore: Function(s) of the Mad1–cyclin B1 complex
Authors: Houston Jack , Lara-Gonzalez Pablo , Desai Arshad
Published: July 2020

In the film Rashomon, four witnesses describe seemingly contradictory views of one event. In a recent analogy, an interaction between the master mitotic regulator cyclin B1 and the spindle checkpoint component Mad1 was independently described by three groups who propose strikingly different functions for this interaction. Here, we summarize their findings and present a perspective on reconciling the different views.
Chemical regulation of Kv7 channels: Diverse scaffolds, sites, and mechanisms of action
Authors: Kurata Harley T.
Published: July 2020

Kv7 channels are powerfully regulated by a wide variety of physiological and pharmacological signals. Larsson et al. describe the direct modulation of Kv7 channels by endocannabinoids and explore how combinations of Kv7 activators with distinct subtype specificities might lead to effective and selective drug cocktails.
A role for external Ca2+ in maintaining muscle contractility in periodic paralysis
Authors: Cannon Stephen C.
Published: July 2020

Calcium gluconate has been empirically administered to hasten recovery of force during an episode of periodic paralysis. By using a genetically engineered mouse model, Uwera and colleagues show that low Ca2+ clearly promotes a loss of force in affected muscle, thereby providing the first evidence for the benefit of maintaining normal Ca2+ levels in this disorder.
Integrating CAD, 3D-printing technology and oral communication to enhance students’ physics understanding and disciplinary literacy
Authors: Malmström Hans , Enger Jonas , Karlsteen Magnus , Weidow Jonathan
Published: July 2020

How do engineering physics students come to understand and share their physics learnings as a result of careful integration of oral communication with engineering skills like computer aided design and 3D-printing technology? Based in a sociocognitive theory of situated communication pedagogy, the action research conducted in this study set out to answer this research question in an introductory first-year course in engineering physics. A re-design intervention was planned, overseen, and evaluated by a teaching team comprising three physicists and a communication specialist. The findings—supported by student surveys, reflective field notes from the teachers’ observations, and a focus group interview with students—strongly indicate that the students’ structured oral engagement with disciplinary content confer learning benefits and promote the development of disciplinary (physics) literacy.
Fate assessment of commercial 2D MoS2 aqueous dispersions at physicochemical and toxicological level
Authors: Domi Brixhilda , Bhorkar Kapil , Rumbo Carlos , Sygellou Labrini , Yannopoulos Spyros N , Quesada Roberto , Tamayo-Ramos Juan Antonio
Published: July 2020

The physicochemical properties and the toxicological potential of commercially available MoS2 nanoparticles with different lateral size and degradation stage were studied in the present research work. To achieve this, the structure and stoichiometry of fresh and old aqueous suspensions of micro-MoS2 and nano-MoS2 was analyzed by Raman, while x-ray photoelectron spectroscopy allowed to identify more quantitatively the nature of the formed oxidized species. A, the toxicological impact of the nanomaterials under analysis was studied using adenocarcinomic human alveolar basal epithelial cells (A549 cells) and the unicellular fungus S. cerevisiae as biological models. Cell viability assays and reactive oxygen species (ROS) determinations demonstrated different toxicity levels depending on the cellular model used and in function of the degradation state of the selected commercial nanoproducts. Both MoS2 nanoparticle types induced sublethal damage on the A549 cells though the increase of intracellular ROS levels, while comparable concentrations reduced the viability of yeast cells. In addition, the old MoS2 nanoparticles suspensions exhibited a higher toxicity for both human and yeast cells than the fresh ones. Our findings demonstrate that the fate assessment of nanomaterials is a critical aspect to increase the understanding on their characteristics and on their potential impact on biological systems along their life cycle.
A portable device with low-power consumption for monitoring mouse vital signs during in vivo photoacoustic imaging and photothermal therapy
Authors: Phan Duc Tri , Phan Thi Tuong Vy , Bui Ngoc Thang , Park Sumin , Choi Jaeyeop , Oh Junghwan
Published: July 2020

Objective: The aim of this study was to monitor the physiological changes and cytotoxic effects of exogenous contrast agents during photoacoustic imaging (PAI) and photothermal therapy (PTT). In this paper, a low-power telemetric device for mouse vital signs monitoring was designed and demonstrated. Approach: The power consumption was optimized through hardware and software co-design with a 17% increased operating time compared with typical operation. To demonstrate the feasibility of the monitoring device, PAI and PTT experiments with chitosan-polypyrrole nanocomposites (CS-PPy NCs) as exogenous contrast agents were conducted. Herein, the physiological variation in groups of mice with different CS-PPy NC concentrations was observed and analyzed. Main results: The experimental results indicated the influence of CS-PPy NCs and anesthesia on mouse vital signs in PAI and PTT. Additionally, the association between core temperature, heart rate, and saturation of peripheral oxygen (SpO2) during PAI and PTT was shown. The strong near-infrared absorbance of exogenous contrast agents could account for the increase in mouse core temperature and tumor temperature in this study. Furthermore, high cross-correlation values between core temperature, heart rate, and SpO2 were demonstrated to explain the fluctuation of mouse vital signs during PAI and PTT. Significance: A design of a vital signs monitoring device, with low power consumption, was introduced in this study. A high cross correlation coefficient of mouse vital signs and the effects of CS-PPy NCs were observed, which explained the mouse physiological variation during the PAI and PTT experiments.
Simulation and analysis of III–V heterostructure solar cells for a continuous HVPE process
Authors: Yao Min , Rawlings James B , Kuech Thomas F
Published: July 2020

A continuous hydride vapor phase epitaxy (HVPE) growth system has the potential to realize large-scale production of low-cost III–V solar cells. To aid the process development, this work integrates HVPE reactor model with III–V solar cell simulation to intimately tie the device performance to the process design and operation. This modeling approach sets a potential to connect the control of a growth system directly to the device performance without intervening ancillary models. The approach of direct process-to-device level simulation is demonstrated through simulating the continuous HVPE fabrication of a model solar cell structure as a function of critical process parameter. Critical reactor design features as well as sensitive material parameters in affecting device performance are discussed. An illustrative case study is carried out to investigate the influence of gas curtain velocity on the solar cell efficiency using the integration of reactor and solar cell models. Through the correlations determined by the process-to-device simulations, the sensitivity of critical reactor variables in affecting cell efficiency can be established and optimized through the impact on solar cell performance directly. This integrated device performance–reactor design approach allows for the design of the process and its real-time control with direct knowledge of the expected dependence of device performance on reactor design trade-offs.
On the microstructure and superelastic evolution of laser annealed thin NiTinol wires
Authors: Biffi C A , Coduri M , Tuissi A
Published: July 2020

Shape setting is a crucial step of the production route of shape memory alloys (SMAs) elements for fixing their functional properties. For thin SMA wires, this peculiar setting can be performed by a laser beam scanning the wire length. In the present work the correlation among the functional properties, such as stress–strain curves, the microstructural properties and the laser power was studied on 100 μm pseudoelastic NiTi wire. A comparison between the performances of the laser treated and the commercial wires was discussed. It can be stated that the wire responses can be modulated as a function of the laser power; the optimal laser condition can induce functional properties at least comparable to the ones of the wire conventionally treated in a furnace. Laser induced superelasticity was obtained at room temperature and the corresponding microstructure suggests a texture effect associated with the directional and fast heating induced by the laser beam scan. A favorable condition for extended stress induced plateau lengths, compared to the one of the commercially available furnace treated wires, was induced by the laser scan.
Effect of meso-scale structures and hyper-viscoelastic mechanics on the nonlinear tensile stability and hysteresis of woven materials
Authors: Sun Fengxin , Hu Xiaorui
Published: July 2020

Woven textiles are not only a craft and industrial product but also a thousand-year-old crystallization of human technology. However, the highly sought after mechanical behavior of fabric, generally undergoing large structural distortion along with material deformation even under small stress, is still not clearly understood despite a growing interest in emerging applications, such as flexible electron devices, biomedicine and other engineering fields. Herein, a numerical methodology was introduced to strengthen the comprehensive understanding of the synergy effect of material mechanics and mesostructures of woven materials. A hyper-viscoelastic constitutive model for yarn materials was proposed, and a meso-scale geometry model captured from a resin-cured woven fabric was used, down to micron-sized weaving structures, to investigate the uniaxial loading and unloading process based on finite element (FE) method. The tensile and hysteresis mechanics was identified based on the validated FE model and parameter study of friction effect and fabric structures. The nonlinear tensile and recovery behaviors were reasonably represented by the developed models and the synergistic effect of inner yarn friction and viscoelasticity on the hysteresis was proved. This study can provide an effective method to analyze and predict the nonlinear tensile and hysteresis behavior of woven fabric, laying down the way to textile-based strain sensing materials by enhancing our design and tuning capabilities of the dimension stability of woven materials under tension.
Rapid crystal growth of triple-layered cuprate superconductor HgBa2Ca2Cu3O8+δ
by cesium chloride additional method
Authors: Hara Hiroshi , Adachi Shintaro , Matsumoto Ryo , Saito Yoshito , Yamamoto Sayaka , Takeya Hiroyuki , Takano Yoshihiko
Published: July 2020

We have developed the rapid growth method for HgBa2Ca2Cu3O8+δ
(Hg-1223) by using a sealed quartz tube technique with a small amount of cesium chloride (CsCl). Our results suggested that a small amount of CsCl works as a flux during the crystal growth of Hg-1223. The developed method achieved the growth of the Hg-1223 single crystal pieces in 4 h. Furthermore, the grown single crystals showed high purity. The developed method is useful for application purposes such as high transition-temperature (T
c) superconducting cable.
PEWO: a collection of workflows to benchmark phylogenetic placement
Authors: Linard Benjamin , Romashchenko Nikolai , Pardi Fabio , Rivals Eric
Published: July 2020

Motivation

Phylogenetic placement (PP) is a process of taxonomic identification for which several tools are now available. However, it remains difficult to assess which tool is more adapted to particular genomic data or a particular reference taxonomy. We developed Placement Evaluation WOrkflows (PEWO), the first benchmarking tool dedicated to PP assessment. Its automated workflows can evaluate PP at many levels, from parameter optimization for a particular tool, to the selection of the most appropriate genetic marker when PP-based species identifications are targeted. Our goal is that PEWO will become a community effort and a standard support for future developments and applications of PP.

Availability and implementation

https://github.com/phylo42/PEWO.

Supplementary information

Supplementary data are available at Bioinformatics online.
Cell2Chem: mining explored and unexplored biosynthetic chemical spaces
Authors: Liu Dongliang , Han Mengying , Tian Yu , Gong Linlin , Jia Cancan , Cai Pengli , Tu Weizhong , Chen Junni , Hu Qian-Nan
Published: July 2020

Living cell strains have important applications in synthesizing their native compounds and potential for use in studies exploring the universal chemical space. Here, we present a web server named as Cell2Chem which accelerates the search for explored compounds in organisms, facilitating investigations of biosynthesis in unexplored chemical spaces. Cell2Chem uses co-occurrence networks and natural language processing to provide a systematic method for linking living organisms to biosynthesized compounds and the processes that produce these compounds. The Cell2Chem platform comprises 40 370 species and 125 212 compounds. Using reaction pathway and enzyme function in silico prediction methods, Cell2Chem reveals possible biosynthetic pathways of compounds and catalytic functions of proteins to expand unexplored biosynthetic chemical spaces. Cell2Chem can help improve biosynthesis research and enhance the efficiency of synthetic biology.

Availability and implementation

Cell2Chem is available at: http://www.rxnfinder.org/cell2chem/.
A Severe Lack of Evidence Limits Effective Conservation of the World's Primates
Authors: Junker Jessica , Petrovan Silviu O , Arroyo-RodrÍguez Victor , Boonratana Ramesh , Byler Dirck , Chapman Colin A , Chetry Dilip , Cheyne Susan M , Cornejo Fanny M , CortÉs-Ortiz Liliana , Cowlishaw Guy , Christie Alec P , Crockford Catherine , Torre Stella De La , De Melo Fabiano R , Fan P , Grueter Cyril C , GuzmÁn-Caro Diana C , Heymann Eckhard W , Herbinger Ilka , Hoang Minh D , Horwich Robert H , Humle Tatyana , Ikemeh Rachel A , Imong Inaoyom S , Jerusalinsky Leandro , Johnson Steig E , Kappeler Peter M , Kierulff Maria CecÍlia M , KonÉ Inza , Kormos Rebecca , Le Khac Q , Li Baoguo , Marshall Andrew J , Meijaard Erik , Mittermeier Russel A , Muroyama Yasuyuki , Neugebauer Eleonora , Orth Lisa , Palacios Erwin , Papworth Sarah K , Plumptre Andrew J , Rawson Ben M , Refisch Johannes , Ratsimbazafy Jonah , Roos Christian , Setchell Joanna M , Smith Rebecca K , Sop Tene , Schwitzer Christoph , Slater Kathy , Strum Shirley C , Sutherland William J , Talebi MaurÍcio , Wallis Janette , Wich Serge , Williamson Elizabeth A , Wittig Roman M , KÜhl Hjalmar S
Published: July 2020

Threats to biodiversity are well documented. However, to effectively conserve species and their habitats, we need to know which conservation interventions do (or do not) work. Evidence-based conservation evaluates interventions within a scientific framework. The Conservation Evidence project has summarized thousands of studies testing conservation interventions and compiled these as synopses for various habitats and taxa. In the present article, we analyzed the interventions assessed in the primate synopsis and compared these with other taxa. We found that despite intensive efforts to study primates and the extensive threats they face, less than 1% of primate studies evaluated conservation effectiveness. The studies often lacked quantitative data, failed to undertake postimplementation monitoring of populations or individuals, or implemented several interventions at once. Furthermore, the studies were biased toward specific taxa, geographic regions, and interventions. We describe barriers for testing primate conservation interventions and propose actions to improve the conservation evidence base to protect this endangered and globally important taxon.
A Pilot Programme to Facilitate the Use of Mental Health Treatment Requirements: Professional Stakeholders’ Experiences
Authors: Molyneaux Emma , Vera San Juan Norha , Brown Penelope , Lloyd-Evans Bryn , Oram Sian
Published: July 2020

Mental Health Treatment Requirements (MHTRs) have been available in England and Wales since 2005 but are rarely used, despite high rates of mental health problems amongst offenders. In 2018, a new protocol to facilitate the use of MHTRs was piloted in five sites in England. Aims: Understanding the experiences of professional stakeholders and identify barriers to use MHTRs. Methods: Semi-structured qualitative interviews were conducted with thirty-eight professional stakeholders and thematic analysis applied. Results: Interviewees were positive about the content and implementation of the new protocol. Interviewees described key benefits as increasing options in community sentencing, addressing a gap in service provision and facilitating offenders’ access to other services. Challenges described, included multi-agency working, sustainability of funding and the range and complexity of needs of offenders receiving MHTRs and the variation in their motivation to engage. Success factors described were having a strong steering group, staff dedicated to the project and being able to provide a broad range of support to meet offender needs. Conclusion: The MHTR pilot protocol was generally well-received and appeared to address previous barriers to the use of MHTRs. Future work is needed to evaluate the effectiveness of MHTRs and the experience of offenders who receive them.
Age Differences In Retrieval-Related Reinstatement Reflect Age-Related Dedifferentiation At Encoding
Authors: Hill Paul F , King Danielle R , Rugg Michael D
Published: July 2020

Age-related reductions in neural selectivity have been linked to cognitive decline. We examined whether age differences in the strength of retrieval-related cortical reinstatement could be explained by analogous differences in neural selectivity at encoding, and whether reinstatement was associated with memory performance in an age-dependent or an age-independent manner. Young and older adults underwent fMRI as they encoded words paired with images of faces or scenes. During a subsequent scanned memory test participants judged whether test words were studied or unstudied and, for words judged studied, also made a source memory judgment about the associated image category. Using multi-voxel pattern similarity analyses, we identified robust evidence for reduced scene reinstatement in older relative to younger adults. This decline was however largely explained by age differences in neural differentiation at encoding; moreover, a similar relationship between neural selectivity at encoding and retrieval was evident in young participants. The results suggest that, regardless of age, the selectivity with which events are neurally processed at the time of encoding can determine the strength of retrieval-related cortical reinstatement.
Binding of Dopamine D1 Receptor and Noradrenaline Transporter in Individuals with Autism Spectrum Disorder: A PET Study
Authors: Kubota Manabu , Fujino Junya , Tei Shisei , Takahata Keisuke , Matsuoka Kiwamu , Tagai Kenji , Sano Yasunori , Yamamoto Yasuharu , Shimada Hitoshi , Takado Yuhei , Seki Chie , Itahashi Takashi , Aoki Yuta Y , Ohta Haruhisa , Hashimoto Ryu-ichiro , Zhang Ming-Rong , Suhara Tetsuya , Nakamura Motoaki , Takahashi Hidehiko , Kato Nobumasa , Higuchi Makoto
Published: July 2020

Although previous studies have suggested the involvement of dopamine (DA) and noradrenaline (NA) neurotransmissions in the autism spectrum disorder (ASD) pathophysiology, few studies have examined these neurotransmissions in individuals with ASD in vivo. Here, we investigated DA D1 receptor (D1R) and noradrenaline transporter (NAT) binding in adults with ASD (n = 18) and neurotypical controls (n = 20) by utilizing two different PET radioligands, [11C]SCH23390 and (S,S)-[18F]FMeNER-D2, respectively. We found no significant group differences in DA D1R (striatum, anterior cingulate cortex, and temporal cortex) or NAT (thalamus and pons) binding. However, in the ASD group, there were significant negative correlations between DA D1R binding (striatum, anterior cingulate cortex and temporal cortex) and the “attention to detail” subscale score of the Autism Spectrum Quotient. Further, there was a significant positive correlation between DA D1R binding (temporal cortex) and emotion perception ability assessed by the neurocognitive battery. Associations of NAT binding with empathic abilities and executive function were found in controls, but were absent in the ASD group. Although a lack of significant group differences in binding might be partly due to the heterogeneity of ASD, our results indicate that central DA and NA function might play certain roles in the clinical characteristics of ASD.
Integrative Genomic Enrichment Analysis Identified the Brain Regions and Development Stages Related to Anorexia Nervosa and Obsessive-Compulsive Disorder
Authors: Cheng Bolun , Qi Xin , Liang Chujun , Zhang Lu , Ma Mei , Li Ping , Liu Li , Cheng Shiqiang , Yao Yao , Chu Xiaomeng , Ye Jing , Wen Yan , Jia Yumeng , Zhang Feng
Published: July 2020

Our aim is to explore the spatial and temporal features of anorexia nervosa (AN) and obsessive-compulsive disorder (OCD) considering different brain regions and development stages. The gene sets related to 16 brain regions and nine development stages were obtained from a brain spatial and temporal transcriptomic dataset. Using the genome-wide association study data, transcriptome-wide association study (TWAS) was conducted to identify the genes whose imputed expressions were associated with AN and OCD, respectively. The mRNA expression profiles were analyzed by GEO2R to obtain differentially expressed genes. Gene set enrichment analysis was conducted to detect the spatial and temporal features related to AN and OCD using the TWAS and mRNA expression analysis results. We observed multiple common association signals shared by TWAS and mRNA expression analysis of AN, such as the primary auditory cortex vs. cerebellar cortex in fetal development and earlier vs. later fetal development in the somatosensory cortex. For OCD, we also detected multiple common association signals, such as medial prefrontal cortex vs. amygdala in adulthood and fetal development vs. infancy in mediodorsal nucleus of thalamus. Our study provides novel clues for describing the spatial and temporal features of brain development in the pathogenesis of AN and OCD.
Implications of Test Characteristics and Population Seroprevalence on “Immune Passport” Strategies
Authors: Larremore Daniel B , Bubar Kate M , Grad Yonatan H
Published: July 2020

Various forms of “immune passports” or “antibody certificates” are being considered in conversations around reopening economies after periods of social distancing. A critique of such programs focuses on the uncertainty around whether seropositivity means immunity from repeat infection. However, an additional important consideration is that the low positive predictive value of serological tests in the setting of low population seroprevalence and imperfect test specificity will lead to many false-positive passport holders. Here, we pose a simple question: how many false-positive passports could be issued while maintaining herd immunity in the workforce? Answering this question leads to a simple mathematical formula for the minimum requirements of serological tests for a passport program, which depend on the population prevalence and the value of the basic reproductive number, R0. Our work replaces speculation in the press with rigorous analysis, and will need to be considered in policy decisions that are based on individual and population serology results.
Lessons From Mass-Testing for Coronavirus Disease 2019 in Long-Term Care Facilities for the Elderly in San Francisco
Authors: Louie Janice K , Scott Hyman M , DuBois Amie , Sturtz Natalya , Lu Wendy , Stoltey Juliet , Masinde Godfred , Cohen Stephanie , Sachdev Darpun , Philip Susan , Bobba Naveena , Aragon Tomas ,   San Francisco Department of Public Health COVID-19 Skilled Nursing Facility Outbreak Response Team, Robin Allen-Contreras , Sabrina Alonso , Nicole Copeland , Adam Corona , George Lee , Kaylene Lemen , Melissa Ongpin , Lisa Watson , Sheilah Zarate
Published: July 2020

Coronavirus disease 2019 can cause significant mortality in the elderly in long-term care facilities (LTCF). We describe 4 LTCF outbreaks where mass testing identified a high proportion of asymptomatic infections (4%–41% in healthcare workers and 20%–75% in residents), indicating that symptom-based screening alone is insufficient for monitoring for COVID-19 transmission.
Improving the Delivery of Chronic Opioid Therapy Among People Living With Human Immunodeficiency Virus: A Cluster Randomized Clinical Trial
Authors: Samet Jeffrey H , Tsui Judith I , Cheng Debbie M , Liebschutz Jane M , Lira Marlene C , Walley Alexander Y , Colasanti Jonathan A , Forman Leah S , Root Christin , Shanahan Christopher W , Sullivan Margaret M , Bridden Carly L , Abrams Catherine , Harris Catherine , Outlaw Kishna , Armstrong Wendy S , del Rio Carlos
Published: July 2020

Background

Chronic pain is prevalent among people living with human immunodeficiency virus (PLWH); managing pain with chronic opioid therapy (COT) is common. Human immunodeficiency virus (HIV) providers often diverge from prescribing guidelines.

Methods

This 2-arm, unblinded, cluster-randomized clinical trial assessed whether the Targeting Effective Analgesia in Clinics for HIV (TEACH) intervention improves guideline-concordant care compared to usual care for PLWH on COT. The trial was implemented from 2015 to 2018 with 12-month follow-up at safety-net hospital–based HIV clinics in Boston and Atlanta. We enrolled 41 providers and their 187 patients on COT. Prescribers were randomized 1:1 to either a 12-month intervention consisting of a nurse care manager with an interactive electronic registry, opioid education, academic detailing, and access to addiction specialists or a control condition consisting of usual care. Two primary outcomes were assessed through electronic medical records: ≥2 urine drug tests and any early COT refills by 12 months. Other outcomes included possible adverse consequences.

Results

At 12 months, the TEACH intervention arm had higher odds of ≥2 urine drug tests than the usual care arm (71% vs 20%; adjusted odds ratio [AOR], 13.38 [95% confidence interval {CI}, 5.85–30.60]; P < .0001). We did not detect a statistically significant difference in early refills (22% vs 30%; AOR, 0.55 [95% CI, .26–1.15]; P = .11), pain severity (6.30 vs 5.76; adjusted mean difference, 0.10 [95% CI, −1.56 to 1.75]; P = .91), or HIV viral load suppression (86.9% vs 82.1%; AOR, 1.21 [95% CI, .47–3.09]; P = .69).

Conclusions

TEACH is a promising intervention to improve adherence to COT guidelines without evident adverse consequences.
Parainfluenza Virus Types 1–3 Infections Among Children and Adults Hospitalized With Community-acquired Pneumonia
Authors: Howard Leigh M , Edwards Kathryn M , Zhu Yuwei , Williams Derek J , Self Wesley H , Jain Seema , Ampofo Krow , Pavia Andrew T , Arnold Sandra R , McCullers Jonathan A , Anderson Evan J , Wunderink Richard G , Grijalva Carlos G
Published: July 2020

Background

Parainfluenza virus (PIV) is a leading cause of lower respiratory tract infections. Although there are several distinct PIV serotypes, few studies have compared the clinical characteristics and severity of infection among the individual PIV serotypes and between PIV and other pathogens in patients with community-acquired pneumonia.

Methods

We conducted active population-based surveillance for radiographically confirmed community-acquired pneumonia hospitalizations among children and adults in 8 US hospitals with systematic collection of clinical data and respiratory, blood, and serological specimens for pathogen detection. We compared clinical features of PIV-associated pneumonia among individual serotypes 1, 2, and 3 and among all PIV infections with other viral, atypical, and bacterial pneumonias. We also compared in-hospital disease severity among groups employing an ordinal scale (mild, moderate, severe) using multivariable proportional odds regression.

Results

PIV was more commonly detected in children (155/2354; 6.6%) than in adults (66/2297; 2.9%) (P < .001). Other pathogens were commonly co-detected among PIV cases (110/221; 50%). Clinical features of PIV-1, PIV-2, and PIV-3 infections were similar to one another in both children and adults with pneumonia. In multivariable analysis, children with PIV-associated pneumonia exhibited similar severity to children with other nonbacterial pneumonia, whereas children with bacterial pneumonia exhibited increased severity (odds ratio, 8.42; 95% confidence interval, 1.88–37.80). In adults, PIV-associated pneumonia exhibited similar severity to other pneumonia pathogens.

Conclusions

Clinical features did not distinguish among infection with individual PIV serotypes in patients hospitalized with community-acquired pneumonia. However, in children, PIV pneumonia was less severe than bacterial pneumonia.
Development of Label-Free Immunoassays as Novel Solutions for the Measurement of Monoclonal Antibody Drugs and Antidrug Antibodies
Authors: Luo Yiqi Ruben , Chakraborty Indrani , Lazar-Molnar Eszter , Wu Alan H B , Lynch Kara L
Published: July 2020

Background

Immunoassays based on label-free technologies (label-free immunoassay [LFIA]) offer an innovative approach to clinical diagnostics and demonstrate great promise for therapeutic drug monitoring (TDM) of monoclonal antibody (mAb) drugs. An LFIA measures immunocomplex formation in real time and allows for quantification on initial binding rate, which facilitates fast measurement within a few minutes.

Methods

Based on thin-film interferometry (TFI) technology, open-access LFIAs were developed for the quantification of the mAb drugs adalimumab (ADL) and infliximab (IFX) and for the detection of the antidrug antibodies (ADAs) to the mAb drugs (ADL-ADAs and IFX-ADAs).

Results

The LFIAs for active mAb drugs (ADL and IFX) and for ADAs (ADL-ADAs and IFX-ADAs) were validated. The analytical measurement range (AMR) for both ADL and IFX was from 2 to 100 μg/mL. The AMR for ADL-ADAs was from 5 to 100 μg/mL and for IFX-ADAs was 10 to 100 μg/mL. In the comparison of LFIAs and reporter gene assays, the correlation coefficient was 0.972 for the quantification of ADL and 0.940 for the quantification of IFX. The concordance rate was 90% for the detection of ADL-ADAs and 76% for the detection of IFX-ADAs.

Conclusions

The LFIAs for active mAb drugs and ADAs were appropriate for the TDM of ADL and IFX. The TFI technology has unique advantages compared with other technologies used for the measurement of mAb drugs. Label-free technologies, especially those allowing for open-access LFIAs, have great potential for clinical diagnostics.
Association Between Elevated suPAR, a New Biomarker of Inflammation, and Accelerated Aging
Authors: Rasmussen Line Jee Hartmann , Caspi Avshalom , Ambler Antony , Danese Andrea , Elliott Maxwell , Eugen-Olsen Jesper , Hariri Ahmad R , Harrington HonaLee , Houts Renate , Poulton Richie , Ramrakha Sandhya , Sugden Karen , Williams Benjamin , Moffitt Terrie E
Published: July 2020

Background

To understand and measure the association between chronic inflammation, aging, and age-related diseases, broadly applicable standard biomarkers of systemic chronic inflammation are needed. We tested whether elevated blood levels of the emerging chronic inflammation marker soluble urokinase plasminogen activator receptor (suPAR) were associated with accelerated aging, lower functional capacity, and cognitive decline.

Methods

We used data from the Dunedin Study, a population-representative 1972–1973 New Zealand birth cohort (n = 1037) that has observed participants to age 45 years. Plasma suPAR levels were analyzed at ages 38 and 45 years. We performed regression analyses adjusted for sex, smoking, C-reactive protein, and current health conditions.

Results

Of 997 still-living participants, 875 (88%) had plasma suPAR measured at age 45. Elevated suPAR was associated with accelerated pace of biological aging across multiple organ systems, older facial appearance, and with structural signs of older brain age. Moreover, participants with higher suPAR levels had greater decline in physical function and cognitive function from childhood to adulthood compared to those with lower suPAR levels. Finally, improvements in health habits between ages 38 and 45 (smoking cessation or increased physical activity) were associated with less steep increases in suPAR levels over those years.

Conclusions

Our findings provide initial support for the utility of suPAR in studying the role of chronic inflammation in accelerated aging and functional decline.
Epigenetic hallmarks of age-related macular degeneration are recapitulated in a photosensitive mouse model
Authors: Luu Jennings , Kallestad Les , Hoang Thanh , Lewandowski Dominik , Dong Zhiqian , Blackshaw Seth , Palczewski Krzysztof
Published: July 2020

Age-related macular degeneration (AMD) is a chronic, multifactorial disorder and a leading cause of blindness in the elderly. Characterized by progressive photoreceptor degeneration in the central retina, disease progression involves epigenetic changes in chromatin accessibility resulting from environmental exposures and chronic stress. Here, we report that a photosensitive mouse model of acute stress-induced photoreceptor degeneration recapitulates the epigenetic hallmarks of human AMD. Global epigenomic profiling was accomplished by employing an Assay for Transposase-Accessible Chromatin using Sequencing (ATAC-Seq), which revealed an association between decreased chromatin accessibility and stress-induced photoreceptor cell death in our mouse model. The epigenomic changes induced by light damage include reduced euchromatin and increased heterochromatin abundance, resulting in transcriptional and translational dysregulation that ultimately drives photoreceptor apoptosis and an inflammatory reactive gliosis in the retina. Of particular interest, pharmacological inhibition of histone deacetylase 11 (HDAC11) and suppressor of variegation 3–9 homolog 2 (SUV39H2), key histone-modifying enzymes involved in promoting reduced chromatin accessibility, ameliorated light damage in our mouse model, supporting a causal link between decreased chromatin accessibility and photoreceptor degeneration, thereby elucidating a potential new therapeutic strategy to combat AMD.
Quality in practice: applying the patient inventory method at a Danish psychiatric hospital
Authors: Hermansen Sabina Bay , Holmskov Jens , Johnsen Søren Paaske , Mainz Jan , Knudsen Søren Valgreen
Published: July 2020

Quality problem

Patient care pathways should be organized according to the needs of the patients. This requires methods to assess whether the specific pathways ensure the right care for the right person at the right time and in the right setting.

Initial assessment

Previous investigations indicate that ~25% of the patients in Danish hospitals experience inappropriate elements in their care pathways.

Choice of solution

This study applied the Patient Inventory method to identify inappropriate elements in care pathways in 15 psychiatric in-patient wards in Denmark.

Implementation

The pathway for 201 patients was systematically evaluated by the clinical staff to identify whether the admission of the patient was avoidable, the hospitalization was unnecessarily prolonged or if the patient could receive more relevant treatment elsewhere. A subsequent meeting between the clinical staff and management qualified the assessment and identified possible solutions to problems.

Evaluation

A total of 54 (26.9%) of the included patients were assessed to have inappropriate elements in their care pathways, some with more than one type, resulting in a total of 65 episodes.

Eight of these episodes (13.1%) were admissions considered to be avoidable, 26 (42.2%) were unnecessary prolongation of admissions, and 31 (58.1%) were patients assessed to be able to receive more relevant care elsewhere.

Lessons learned

One out of four assessed patients admitted to a psychiatric ward was exposed to an inappropriate element in their care pathway. The Patient Inventory tool can assist in a structured dialogue between clinical staff and management to identify focus areas for improvement efforts.
I Own, So I Help Out: How Psychological Ownership Increases Prosocial Behavior
Authors: Jami Ata , Kouchaki Maryam , Gino Francesca
Published: July 2020

This article explores the consequences of psychological ownership going beyond the specific relationship with the possession to guide behavior in unrelated situations. Across seven studies, we find that psychological ownership leads to a boost in self-esteem, which encourages individuals to be more altruistic. In addition, we show that the effect of psychological ownership on prosocial behavior is not driven by self-efficacy, perceived power, reciprocity, feeling well-off, or affect. Examining materialism and mine-me sensitivity as individual differences moderating the effect of psychological ownership on prosocial behavior, we find that the effect does not hold for individuals low on materialism or mine-me sensitivity. Finally, we attenuate the effect of psychological ownership on prosocial tendencies by making the negative attributes of one’s possessions relevant.
Nitric oxide, other reactive signalling compounds, redox, and reductive stress
Authors: Hancock John T , Veal David
Published: July 2020

Nitric oxide (NO) and other reactive nitrogen species (RNS) are key signalling molecules in plants, but they do not work in isolation. NO is produced in cells, often increased in response to stress conditions, but many other reactive compounds used in signalling are generated and accumulate spatially and temporally together. This includes the reactive oxygen species (ROS), such as hydrogen peroxide (H2O2), and hydrogen sulfide (H2S). Here, the interactions with such other reactive molecules is briefly reviewed. Furthermore, along with ROS and H2S, NO will potentially contribute to the overall intracellular redox of the cell. However, RNS will exist in redox couples and therefore the influence of the cellular redox on such couples will be explored. In discussions of the aberrations in intracellular redox it is usually oxidation, so-called oxidative stress, which is discussed. Here, we consider the notion of reductive stress and how this may influence the signalling which may be mediated by NO. By getting a more holistic view of NO biology, the influence on cell activity of NO and other RNS can be more fully understood, and may lead to the elucidation of methods for NO-based manipulation of plant physiology, leading to better stress responses and improved crops in the future.
NIHAO XXIV: rotation- or pressure-supported systems? Simulated Ultra Diffuse Galaxies show a broad distribution in their stellar kinematics
Authors: Cardona-Barrero Salvador , Di Cintio Arianna , Brook Christopher B A , Ruiz-Lara Tomas , Beasley Michael A , Falcón-Barroso Jesus , Macciò Andrea V
Published: July 2020

In recent years, a new window on galaxy evolution opened, thanks to the increasing discovery of galaxies with a low-surface brightness, such as Ultra Diffuse Galaxies (UDGs). The formation mechanism of these systems is still a much debated question and so are their kinematical properties. In this work, we address this topic by analysing the stellar kinematics of isolated UDGs formed in the hydrodynamical simulation suite Numerical Investigation of a Hundred Astrophysical Objects (NIHAO). We construct projected line-of-sight velocity and velocity dispersion maps to compute the projected specific angular momentum, λR, to characterize the kinematical support of the stars in these galaxies. We found that UDGs cover a broad distribution, ranging from dispersion to rotation-supported galaxies, with similar abundances in both regimes. The degree of rotation support of simulated UDGs correlates with several properties such as galaxy morphology, higher H i fractions, and larger effective radii with respect to the dispersion-supported group, while the dark matter halo spin and mass accretion history are similar among the two populations. We demonstrate that the alignment of the infalling baryons into the protogalaxy at early z is the principal driver of the z = 0 stellar kinematic state: pressure-supported isolated UDGs form via misaligned gas accretion while rotation-supported ones build up their baryons in an ordered manner. Accounting for random inclination effects, we predict that a comprehensive survey will find nearly half of field UDGs to have rotationally supported stellar discs, when selecting UDGs with effective radius larger than 1 kpc.
On the accretion of a new group of galaxies on to Virgo: I. Internal kinematics of nine in-falling dEs
Authors: Bidaran Bahar , Pasquali Anna , Lisker Thorsten , Coccato Lodovico , Falcón-Barroso Jesus , van de Ven Glenn , Peletier Reynier , Emsellem Eric , Grebel Eva K , La Barbera Francesco , Janz Joachim , Sybilska Agnieszka , Vijayaraghavan Rukmani , Gallagher John , Gadotti Dimitri A
Published: July 2020

Galaxy environment has been shown to play an important role in transforming late-type, star-forming galaxies to quiescent spheroids. This transformation is expected to be more severe for low-mass galaxies ($M \lt 10^{10}\, \mathrm{M}_\odot$) in dense galaxy groups and clusters, mostly due to the influence of their past host haloes (also known as pre-processing) and their present-day environments. For the first time, in this study, we investigate a sample of nine early-type dwarf galaxies (dEs) that were accreted as a likely bound group on to the Virgo galaxy cluster about 2–3 Gyr ago. Considering this special condition, these nine dEs may provide a test bed for distinguishing between the influence of the Virgo galaxy cluster and the effects of the previous host halo on their current properties. Specifically, we use VLT/MUSE integral-field unit spectra to derive their kinematics and specific angular momentum (λR) profiles. We observe a spread in the λR profiles of our sample dEs, finding that the λR profiles of half of them are as high as those of low-mass field galaxies. The remaining dEs exhibit λR profiles as low as those of Virgo dEs that were likely accreted longer ago. Moreover, we detect nebular emission in one dE with a gas velocity offset suggesting ongoing gas stripping in Virgo. We suggest that the low-λR dEs in our sample were processed by their previous host halo, prior to their infall to Virgo, and that the high-λR dEs may be experiencing ram pressure stripping in Virgo.