bluuebunny/crossref_metadata_2025 huggingface dataset:
Seeing the mind of robots: Harm augments mind perception but benevolent intentions reduce dehumanisation of artificial entities in visual vignettes
Authors: Küster Dennis , Swiderska Aleksandra
Published: September 2020

According to moral typecasting theory, good‐ and evil‐doers (agents) interact with the recipients of their actions (patients) in a moral dyad. When this dyad is completed, mind attribution towards intentionally harmed liminal minds is enhanced. However, from a dehumanisation view, malevolent actions may instead result in a denial of humanness. To contrast both accounts, a visual vignette experiment (N = 253) depicted either malevolent or benevolent intentions towards robotic or human avatars. Additionally, we examined the role of harm‐salience by showing patients as either harmed, or still unharmed. The results revealed significantly increased mind attribution towards visibly harmed patients, mediated by perceived pain and expressed empathy. Benevolent and malevolent intentions were evaluated respectively as morally right or wrong, but their impact on the patient was diminished for the robotic avatar. Contrary to dehumanisation predictions, our manipulation of intentions failed to affect mind perception. Nonetheless, benevolent intentions reduced dehumanisation of the patients. Moreover, when pain and empathy were statistically controlled, the effect of intentions on mind perception was mediated by dehumanisation. These findings suggest that perceived intentions might only be indirectly tied to mind perception, and that their role may be better understood when additionally accounting for empathy and dehumanisation.
Electronic structures of NbGen−/0/+ (n = 1–3) clusters from multiconfigurational CASPT2 and density matrix renormalization group‐CASPT2 calculations
Authors: Tran Van Tan , Tran Quoc Tri
Published: September 2020

Density functional theory and multiconfigurational CASPT2 and density matrix renormalization group DMRG‐CASPT2 have been employed to study the low‐lying states of NbGen−/0/+ (n = 1–3) clusters. With the DMRG‐CASPT2 method, the active spaces are extended to a size of 20 orbitals. For most of the states, the CASPT2 relative energies are comparable with the DMRG‐CASPT2 results. The leading configuration, bond distances, vibrational frequencies, and relative energies of the low‐lying states of these clusters were calculated. The ground states of these clusters were computed to be 3Δ, 4Φ, and 5Φ of NbGe−/0/+; 3A2, 4B1, and 3B1 of cyclic‐NbGe2−/0/+; and 1A′, 12A″ and 12A′′ (2E), and 3A″ of tetrahedral‐NbGe3−/0/+ isomers. For NbGe cluster, our calculations proposed that the 6∑ is almost degenerate with the 4Φ with the CASPT2 and DMRG‐CASPT2 relative energies of 0.05 and 0.06 eV. The adiabatic detachment energies of NbGen− (n = 1–3) clusters were estimated to be 1.46, 1.55, and 2.18 eV by the CASPT2 method. The relevant detachment energies of the anionic ground state and the ionization energies of the neutral ground states are evaluated at the CASPT2 level.
HIV‐1 transmitted drug resistance surveillance: shifting trends in study design and prevalence estimates
Authors: Rhee Soo‐Yon , Kassaye Seble G , Barrow Geoffrey , Sundaramurthi Jagadish Chandrabose , Jordan Michael R , Shafer Robert W
Published: September 2020

Introduction

HIV‐1 transmitted drug resistance (TDR) prevalence increased during the initial years of the antiretroviral therapy (ART) global scale‐up. Few studies have examined recent trends in TDR prevalence using published genetic sequences and described the characteristics of ART‐naïve persons from whom these published sequences have been obtained.

Methods

We identified 125 studies published between 2014 and 2019 for which HIV‐1 reverse transcriptase (RT) with or without protease from ≥50 ART‐naïve adult persons were submitted to the GenBank sequence database. The population characteristics and TDR prevalence were compared to those in 122 studies published in the preceding five years between 2009 and 2013. TDR prevalence was analysed using median study‐level and person‐level data.

Results and discussion

The 2009 to 2013 and 2014 to 2019 studies reported sequence data from 32,866 and 41,724 ART‐naïve persons respectively. Studies from the low‐ and middle‐income country (LMIC) regions in sub‐Saharan Africa, South/Southeast Asia and Latin America/Caribbean accounted for approximately two‐thirds of the studies during each period. Between the two periods, the proportion of studies from sub‐Saharan Africa and from South/Southeast Asia countries other than China decreased from 43% to 32% and the proportion of studies performed at sentinel sites for recent HIV‐1 infection decreased from 33% to 22%. Between 2014 and 2019, median study‐level TDR prevalence was 4.1% in South/Southeast Asia, 6.0% in sub‐Saharan Africa, 9.1% in Latin America/Caribbean, 8.5% in Europe and 14.2% in North America. In the person‐level analysis, there was an increase in overall, NNRTI and two‐class NRTI/NNRTI resistance in sub‐Saharan Africa; an increase in NNRTI resistance in Latin America/Caribbean, and an increase in overall, NNRTI and PI resistance in North America.

Conclusions

Overall, NNRTI and dual NRTI/NNRTI‐associated TDR prevalence was significantly higher in sub‐Saharan Africa studies published between 2014 and 2019 compared with those published between 2009 and 2013. The decreasing proportion of studies from the hardest hit LMIC regions and the shift away from sentinel sites for recent infection suggests that global TDR surveillance efforts and publication of findings require renewed emphasis.
Cytokine release syndrome in COVID-19: Innate immune, vascular, and platelet pathogenic factors differ in severity of disease and sex
Authors: Petrey Aaron C , Qeadan Fares , Middleton Elizabeth A , Pinchuk Irina V , Campbell Robert A , Beswick Ellen J
Published: September 2020

COVID-19 rapidly emerged as a crippling public health crisis in the last few months, which has presented a series health risk. Understanding of the immune response and biomarker analysis is needed to progress toward understanding disease pathology and developing improved treatment options. The goal of this study is to identify pathogenic factors that are linked to disease severity and patient characteristics. Patients with COVID-19 who were hospitalized from March 17 to June 5, 2020 were analyzed for clinical features of disease and soluble plasma cytokines in association with disease severity and sex. Data from COVID-19 patients with acute illness were examined along with an age- and gender-matched control cohort. We identified a group of 16 soluble factors that were found to be increased in COVID-19 patients compared to controls, whereas 2 factors were decreased. In addition to inflammatory cytokines, we found significant increases in factors known to mediate vasculitis and vascular remodeling (PDGF-AA, PDGF-AB-BB, soluble CD40L (sCD40L), FGF, and IP10). Four factors such as platelet-derived growth factors, fibroblast growth factor-2, and IFN-γ-inducible protein 10 were strongly associated with severe disease and ICU admission. Th2-related factors (IL-4 and IL-13) were increased with IL-4 and sCD40L present at increased levels in males compared with females. Our analysis revealed networking clusters of cytokines and growth factors, including previously unknown roles of vascular and stromal remodeling, activation of the innate immunity, as well activation of type 2 immune responses in the immunopathogenesis of COVID-19. These data highlight biomarker associations with disease severity and sex in COVID-19 patients.
Developmental morphology and evolution of extraembryonic membranes of lizards and snakes (Reptilia, Squamata)
Authors: Stewart James R.
Published: September 2020

Amniote embryos are supported and nourished by a suite of tissues, the extraembryonic membranes, that provide vascular connections to the egg contents. Oviparous reptiles share a basic pattern of development inherited from a common ancestor; a vascular chorioallantoic membrane, functioning as a respiratory organ, contacts the eggshell and a vascular yolk sac membrane conveys nutrients to the embryo. Squamates (lizards, snakes) have evolved a novel variation in morphogenesis of the yolk sac that results in a unique structure, the yolk cleft/isolated yolk mass complex. This structure is a source of phylogenetic variation in architecture of the extraembryonic membranes among oviparous squamates. The yolk cleft/isolated yolk mass complex is retained in viviparous species and influences placental architecture. The aim of this paper is to review extraembryonic membrane development and morphology in oviparous and related viviparous squamates to explore patterns of variation. The survey includes all oviparous species for which data are available (11 species; 4 families). Comparisons with viviparous species encompass six independent origins of viviparity. The comparisons reveal that both phylogeny and reproductive mode influence variation in extraembryonic membrane development and that phylogenetic variation influences placental evolution. Models of the evolution of squamate placentation have relied primarily on comparisons between independently derived viviparous species. The inclusion of oviparous species in comparative analyses largely supports these models, yet exposes convergent patterns of evolution that become apparent when phylogenetic variation is recognized.
Methotrexate inhibits SARS‐CoV‐2 virus replication “in vitro”
Authors: Caruso Arnaldo , Caccuri Francesca , Bugatti Antonella , Zani Alberto , Vanoni Marco , Bonfanti Paolo , Cazzaniga Marina E. , Perno Carlo F. , Messa Cristina , Alberghina Lilia
Published: September 2020

In early 2020 the new respiratory syndrome COVID‐19 (caused by the zoonotic SARS‐CoV‐2 virus) spread like a pandemic, starting from Wuhan, China, causing severe economic depression. Despite some advances in drug treatments of medical complications in the later stages of the disease, the pandemic's death toll is tragic, as no vaccine or specific antiviral treatment is currently available. By using a systems approach, we identify the host‐encoded pathway, which provides ribonucleotides to viral RNA synthesis, as a possible target. We show that methotrexate, an FDA‐approved inhibitor of purine biosynthesis, potently inhibits viral RNA replication, viral protein synthesis, and virus release. The effective antiviral methotrexate concentrations are similar to those used for established human therapies using the same drug. Methotrexate should be most effective in patients at the earliest appearance of symptoms to effectively prevent viral replication, diffusion of the infection, and possibly fatal complications.
Research progress and challenges to coronavirus vaccine development
Authors: Zhou Peiwen , Li Zonghui , Xie Linqing , An Dong , Fan Yaohua , Wang Xiao , Li Yiwei , Liu Xiaohong , Wu Jianguo , Li Geng , Li Qin
Published: September 2020

Coronaviruses (CoVs) are nonsegmented, single‐stranded, positive‐sense RNA viruses highly pathogenic to humans. Some CoVs are known to cause respiratory and intestinal diseases, posing a threat to the global public health. Against this backdrop, it is of critical importance to develop safe and effective vaccines against these CoVs. This review discusses human vaccine candidates in any stage of development and explores the viral characteristics, molecular epidemiology, and immunology associated with CoV vaccine development. At present, there are many obstacles and challenges to vaccine research and development, including the lack of knowledge about virus transmission, pathogenesis, and immune response, absence of the most appropriate animal models.
Racial disparities in local therapy for early stage non‐small‐cell lung cancer
Authors: Lutfi Waseem , Martinez‐Meehan Deirdre , Sultan Ibrahim , Evans Nathaniel , Dhupar Rajeev , Luketich James D. , Christie Neil A. , Okusanya Olugbenga T.
Published: September 2020

Objectives

This study investigated disparities in the delivery of definitive therapy for early stage non‐small‐cell lung cancer (ESNSCLC) between Caucasian (CS) and African American (AA) populations.

Methods

The National Cancer Data Base was queried for AA and CS patients, diagnosed with c stage I Non small cell lung cancer between 2004 and 2015. Trends in surgery, stereotactic ablative radiotherapy (SABR), or external beam radiation therapy (EBRT) were compared. Kaplan–Meier and Cox hazards models were used to compare 5‐year overall survival (5YOS).

Results

A total of 174,338 (90.6%) patients were CS and 18,077 (9.4%) patients were AA. AA patients were less likely to receive surgery (60.3% vs. 66.9%; p < .001) and more likely to receive EBRT (12.4% vs. 10.6%; p < .001); however, there was no significant difference in rates of SABR (8.8% vs. 9.2%; p = .066). From 2004 to 2015, the surgery rates increased for AA patients from 44.4% to 61.8% and for CS patients from 57.6% to 65.6%. AA patients had worse 5YOS on an unadjusted analysis (46.7% vs. 47.9%; p = .009). When adjusted for definitive treatment, AA patients had improved survival (hazard ratio = 0.97, 95% confidence interval = 0.94–0.99).

Conclusion

Improvements in the delivery of surgery and equal utilization of definitive radiation therapy are at least partially responsible for closing the survival gap between AA and CS patients with ESNSCLC.
Unraveling chemical structure of laminar premixed tetralin flames at low pressure with photoionization mass spectrometry and kinetic modeling
Authors: Li Yuyang , Zou Jiabiao , Yuan Wenhao , Cao Chuangchuang , Zhang Yan , Qi Fei , Yang Jiuzhong
Published: September 2020

This work reports an investigation on laminar premixed flames of tetralin at 30 Torr and equivalence ratios of 0.7 and 1.7. Measurements of the chemical structure including identification and mole fraction measurements of free radicals, isomers, and polycyclic aromatic hydrocarbons (PAHs) were performed using synchrotron vacuum ultraviolet photoionization mass spectrometry (SVUV‐PIMS). A kinetic model with 296 species and 1 577 reactions was developed and validated against the flame chemical structure data measured in this work. Modeling analysis reveals the key reaction pathways in tetralin decomposition and PAHs formation. The H‐atom abstraction reactions by H, O, and OH are found to control the consumption of tetralin in the lean flame, while those by H play the dominant role in the rich flame. Indene and naphthalene have very high concentration levels in the rich tetralin flame due to the existence of direct formation pathways from the decomposition of tetralin. The two bicyclic PAHs and their radicals play significant roles in the PAHs growth process of tetralin combustion, which results in the high sooting tendency of tetralin compared to those of alkylbenzenes with smaller or same carbon atom numbers.
Consumer community cognition, brand loyalty, and behaviour intentions within online publishing communities: An empirical study of Epubit in China
Authors: Zhang Zhiqiang , Zheng Lei
Published: September 2020

Online community marketing has become an important strategy for awareness and advocacy in many different sectors, including the publishing industry. Research has confirmed its value in establishing brand awareness and strengthening brand loyalty among consumers. This study investigates the Epubit community as an example of successful community marketing to question how such tactics can be adopted more widely by publishers. Epubit is a Chinese online community for IT hobbyists and has been very successful in engaging its community since 2016. In this study, we surveyed members from the Epubit community to address several hypotheses regarding the behavioural responses of online communities. We obtained 325 questionnaires and on analysis discovered that interactivity, word‐of‐mouth, and informativity (i.e. information exchange) can influence consumers' brand affinity in the online publishing community. We conclude that publishers should emphasize member interaction, encourage user feedback, and focus on the value of shared knowledge and co‐creativity. Although this research investigates at Chinese community, the findings may have application in other regions.
The FACT Network: Philosophy, Evolution, and Management of a Collaborative Coastal Tracking Network
Authors: Young Joy M. , Bowers Mary E. , Reyier Eric A. , Morley Danielle , Ault Erick R. , Pye Jonathan D. , Gallagher Riley M. , Ellis Robert D.
Published: September 2020

The FACT Network (originally the Florida Atlantic Coast Telemetry working group), established in 2007, is a grassroots collaboration that is dedicated to improving the conservation and management of aquatic animals by facilitating data sharing amongst researchers using acoustic telemetry technology, providing a community for scientists, and building stakeholder partnerships. Founded along the eastern Florida coastline, FACT quickly grew in both membership and geographical range to include 93 partner groups along a large portion of the southern U.S. Atlantic seaboard and western Caribbean. This rapid expansion was facilitated by adapting FACT's policies and procedures to meet the growing needs of its members, including implementing an online data sharing system capable of exchanging information with other compatible systems designed by the Ocean Tracking Network (OTN). Less than 13 months from its inception, the FACT database housed 129.5 million detections and metadata for 5,979 tags from 101 projects (85 FACT projects and 16 OTN-based projects). Twice-yearly meetings allow FACT members to interact, building relationships between individuals, which in turn promotes collaboration and data sharing. The success of FACT is attributable to a combination of biogeographical factors; partnerships with the Animal Tracking Network, OTN, and Southeast Coastal Ocean Observing Regional Association; and active membership. In a survey of FACT members, data management services and belonging to a community ranked highest as reasons for joining the network. Future success of the FACT Network will depend on how effectively it can adapt to changing needs and conditions in the scientific landscape. In this paper, we describe the origins, philosophy, and management approach of the FACT Network, with the hope that this information can provide insights into the benefits (and limitations) of future acoustic tracking networks in other regions.
Grouper Tales: Use of Acoustic Telemetry to Evaluate Grouper Movements at Western Dry Rocks in the Florida Keys
Authors: Keller Jessica A , Herbig Jennifer L. , Morley Danielle , Wile Ariel , Barbera Paul , Acosta Alejandro
Published: September 2020

The Western Dry Rocks (WDR) area off Key West, Florida, is an open fishing area that contains a multispecies fish spawning aggregation site, but grouper spawning there has yet to be confirmed. The movements of 18 adult and subadult grouper at WDR were tracked using acoustic telemetry to determine how this area is used by grouper species and whether it contains a grouper spawning aggregation site. Tagged fish consisted of 10 Black Grouper Mycteroperca bonaci, 5 Nassau Grouper Epinephelus striatus, 2 Gag M. microlepis, and 1 Yellowfin Grouper M. venenosa. Overall, tagged grouper were more likely to be present in the WDR array during winter spawning months, with species-specific seasonal differences. Our results indicated that grouper presence increased during spawning months, although some adults and subadults were present year-round. Grouper made more movements per day during non-spawning months compared to spawning months, although the north side of WDR was the most heavily used area, regardless of the time of year. Additionally, spatial graphs of grouper movement suggested that different grouper species utilized different areas of WDR. Increased presence of grouper during spawning months suggests that the WDR area may contain a grouper spawning aggregation site, which would mean that fish species aggregate to spawn at this location year-round. The success of the Florida Keys fisheries critically depends on the protection of multispecies spawning aggregations like that potentially contained at WDR.
Automated Analysis of Diffusion‐Weighted Magnetic Resonance Imaging for the Differential Diagnosis of Multiple System Atrophy from Parkinson's Disease
Authors: Krismer Florian , Beliveau Vincent , Seppi Klaus , Mueller Christoph , Goebel Georg , Gizewski Elke R. , Wenning Gregor K. , Poewe Werner , Scherfler Christoph
Published: September 2020

Background

Manual region‐of‐interest analysis of putaminal and middle cerebellar peduncle diffusivity distinguishes patients with multiple system atrophy (MSA) and Parkinson's disease (PD) with high diagnostic accuracy. However, a recent meta‐analysis found substantial between‐study heterogeneity of diagnostic accuracy due to the lack of harmonized imaging protocols and standardized analyses pipelines.

Objective

Evaluation of diagnostic accuracy of observer‐independent analysis of microstructural integrity as measured by diffusion‐tensor imaging in patients with MSA and PD.

Methods

A total of 29 patients with MSA and 19 patients with PD (matched for age, gender, and disease duration) with 3 years of follow‐up were investigated with diffusion‐tensor imaging and T1‐weighted magnetic resonance imaging. Automated localization of relevant brain regions was obtained, and mean diffusivity and fractional anisotropy values were averaged within the regions of interest. The classification was performed using a C5.0 hierachical decision tree algorithm.

Results

Mean diffusivity of the middle cerebellar peduncle and cerebellar gray and white matter compartment as well as the putamen were significantly increased in patients with MSA and showed superior effect sizes compared to the volumetric analysis of these regions. A classifier model identified mean diffusivity of the middle cerebellar peduncle and putamen as the most predictive parameters. Cross‐validation of the classification model yields a Cohen's κ and overall diagnostic accuracy of 0.823 and 0.914, respectively.

Conclusion

Analysis of microstructural integrity within the middle cerebellar peduncle and putamen yielded a superior effect size compared to the volumetric measures, resulting in excellent diagnostic accuracy to discriminate patients with MSA from PD in the early to moderate disease stages. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Novel mutation identification and copy number variant detection via exome sequencing in congenital muscular dystrophy
Authors: Cauley Edmund S. , Pittman Alan , Mummidivarpu Swati , Karimiani Ehsan G. , Martinez Samantha , Moroni Isabella , Boostani Reza , Podini Daniele , Mora Marina , Jamshidi Yalda , Hoffman Eric P. , Manzini M. Chiara
Published: September 2020

Background

Congenital muscular dystrophy type 1A (MDC1A), also termed merosin‐deficient congenital muscular dystrophy (CMD), is a severe form of CMD caused by mutations in the laminin α2 gene (LAMA2). Of the more than 300 likely pathogenic variants found in the Leiden Open Variant Database, the majority are truncating mutations leading to complete LAMA2 loss of function, but multiple copy number variants (CNVs) have also been reported with variable frequency.

Methods

We collected a cohort of individuals diagnosed with likely MDC1A and sought to identify both single nucleotide variants and small and larger CNVs via exome sequencing by extending the analysis of sequencing data to detect splicing changes and CNVs.

Results

Standard exome analysis identified multiple novel LAMA2 variants in our cohort, but only four cases carried biallelic variants. Since likely truncating LAMA2 variants are often found in heterozygosity without a second allele, we performed additional splicing and CNV analysis on exome data and identified one splice change outside of the canonical sequences and three CNVs, in the remaining four cases.

Conclusions

Our findings support the expectation that a portion of MDC1A cases may be caused by at least one CNV allele and show how these changes can be effectively identified by additional analysis of existing exome data.
Expression of sirtuins in ovarian follicles of postnatal mice
Authors: Kong Deqi , Yao Guidong , Bai Yucheng , Yang Guang , Xu Ziwen , Kong Yue , Fan Huiying , He Qina , Sun Yingpu
Published: September 2020

Mammalian ovarian follicular development is an intricate, elaborate, and well‐organized phenomenon regulated by various signaling pathways; however, the underlying mechanism remains unclear. Mammalian sirtuins (sirtuin 1 to sirtuin 7) are a group of NAD+‐dependent deacetylases implicated in various physiological processes including cell proliferation, apoptosis, cell cycle progression, and insulin signaling. Mammalian ovarian sirtuins have been studied using adult and aged bovine, porcine, and murine models. However, limited information is available regarding their precise expression patterns and the localization of follicle development in mice. This study aimed to assess the dynamic expression and localization of all seven sirtuins in early postnatal mouse ovaries through real‐time polymerase chain reaction analysis and immunohistochemistry, respectively. During postnatal ovarian follicle development, sirtuin 1, sirtuin 4, and sirtuin 6 were downregulated compared with those in 1‐day postnatal mouse ovaries (p < .05), indicating that these three sirtuin genes may be markers of follicular development. Combining their localization in granulosa cells through immunohistochemical studies, sirtuin 1, sirtuin 4, and sirtuin 6 are suggested to play negative regulatory roles in mammal ovarian follicular granulosa cell development. Furthermore, we found that sirtuin 2 (p < .05) and sirtuin 7 (p < .05) mRNA were constantly upregulated relative to sirtuin 1, although limited information is available regarding sirtuin 7. Among all sirtuins in mouse ovaries, sirtuin 1 was relatively and steadily downregulated. Upon sirtuin 1 overexpression in 1‐day postnatal mouse ovaries via sirtuin 1‐harboring adenoviruses in vitro, the emergence of primary follicles was delayed, as was the emergence of secondary follicles in 4‐day postnatal ovaries. Further studies on KGN cell lines reported that interfering with sirtuin 1 expression in granulosa cell significantly affected granulosa cell proliferation and the expression of mitochondrial genes. This study presents the first systemic analysis of dynamic patterns of sirtuin family expression in early postnatal mice ovaries, laying the foundation for further studies on less discussed sirtuin subtypes, such as sirtuin 5 and sirtuin 7.
MRI‐cytometry: Mapping nonparametric cell size distributions using diffusion MRI
Authors: Xu Junzhong , Jiang Xiaoyu , Devan Sean P. , Arlinghaus Lori R. , McKinley Eliot T. , Xie Jingping , Zu Zhongliang , Wang Qing , Chakravarthy A. Bapsi , Wang Yong , Gore John C.
Published: September 2020

Purpose

This report introduces and validates a new diffusion MRI‐based method, termed MRI‐cytometry, which can noninvasively map intravoxel, nonparametric cell size distributions in tissues.

Methods

MRI was used to acquire diffusion MRI signals with a range of diffusion times and gradient factors, and a model was fit to these data to derive estimates of cell size distributions. We implemented a 2‐step fitting method to avoid noise‐induced artificial peaks and provide reliable estimates of tumor cell size distributions. Computer simulations in silico, experimental measurements on cultured cells in vitro, and animal xenografts in vivo were used to validate the accuracy and precision of the method. Tumors in 7 patients with breast cancer were also imaged and analyzed using this MRI‐cytometry approach on a clinical 3 Tesla MRI scanner.

Results

Simulations and experimental results confirm that MRI‐cytometry can reliably map intravoxel, nonparametric cell size distributions and has the potential to discriminate smaller and larger cells. The application in breast cancer patients demonstrates the feasibility of direct translation of MRI‐cytometry to clinical applications.

Conclusion

The proposed MRI‐cytometry method can characterize nonparametric cell size distributions in human tumors, which potentially provides a practical imaging approach to derive specific histopathological information on biological tissues.
Model‐based reconstruction for simultaneous multi‐slice mapping using single‐shot inversion‐recovery radial FLASH
Authors: Wang Xiaoqing , Rosenzweig Sebastian , Scholand Nick , Holme H. Christian M. , Uecker Martin
Published: September 2020

Purpose

To develop a single‐shot multi‐slice
mapping method by combing simultaneous multi‐slice (SMS) excitations, single‐shot inversion‐recovery (IR) radial fast low‐angle shot (FLASH), and a nonlinear model–based reconstruction method.

Methods

SMS excitations are combined with a single‐shot IR radial FLASH sequence for data acquisition. A previously developed single‐slice calibrationless model–based reconstruction is extended to SMS, formulating the estimation of parameter maps and coil sensitivities from all slices as a single nonlinear inverse problem. Joint‐sparsity constraints are further applied to the parameter maps to improve
precision. Validations of the proposed method are performed for a phantom and for the human brain and liver in 6 healthy adult subjects.

Results

Phantom results confirm good
accuracy and precision of the simultaneously acquired multi‐slice
maps in comparison to single‐slice references. In vivo human brain studies demonstrate the better performance of SMS acquisitions compared to the conventional spoke‐interleaved multi‐slice acquisition using model‐based reconstruction. Aside from good accuracy and precision, the results of 6 healthy subjects in both brain and abdominal studies confirm good repeatability between scan and re‐scans. The proposed method can simultaneously acquire
maps for 5 slices of a human brain (
) or 3 slices of the abdomen (
) within 4 seconds.

Conclusions

The IR SMS radial FLASH acquisition together with a nonlinear model–based reconstruction enable rapid high‐resolution multi‐slice
mapping with good accuracy, precision, and repeatability.
Nanomaterials in wound healing: From material sciences to wound healing applications
Authors: Barroso Andreia , Mestre Henrique , Ascenso Andreia , Simões Sandra , Reis Catarina
Published: September 2020

An increasing number of innovative therapies have emerged in the field of wound healing. Nanostructured systems have been used to improve wound healing at different stages. The drug itself may be formulated at a nanoscale such that it can function as its own “carrier” or nanomaterials may be used as drug delivery vehicles. The present work covers the latest advancements on innovative nano‐based organic and inorganic materials. These novel drug delivery systems possess high stability, large surface area and tunable compositions and have demonstrated their wound‐healing properties using in vitro and in vivo models. Key areas in the development of new systems for wound care are the assessment of biological compatibility, the evaluation of anti‐microbial activity and the in vivo efficacy assessment using full‐thickness skin models. Due to the multifactorial nature of chronic wound occurrence robust models should support the investigation of new materials in order to elucidate mechanisms involved in the sequence of physiologic processes that take place at wound healing. Although several nanoparticles have been successfully tested both in vitro and in vivo, researchers are still investigating the approaches to implementing large scale production of nanotechnological platforms to wound healing treatments.
Factors associated with pessary fitting in women with symptomatic pelvic organ prolapse: A large prospective cohort study
Authors: Ma Congcong , Xu Tao , Kang Jia , Zhang Ye , Ma Yidi , Liang Shuo , Zhu Lan
Published: September 2020

Aim

To identify factors associated with unsuccessful pessary fitting in a large cohort of patients with symptomatic pelvic organ prolapse (POP).

Methods

This prospective observational study included 611 consecutive women with symptomatic POP in a tertiary‐care hospital. Patients were initially fitted with a ring pessary with support. Those who failed were fitted with a Gellhorn pessary. A successful pessary fitting was defined as a patient who was fitted or refitted with a pessary and continued to use it 2 weeks later. Parametric and nonparametric tests were used for the data analysis.

Results

A total of 524 patients had successful pessary fittings (85.8% success rate). The success rate of the ring pessary with support was 57.9%, of the Gellhorn pessary was 69.1%. Stage IV prolapse (odds ratio [OR], 2.12), posterior compartment prolapse (OR, 1.92), genital hiatus (OR, 1.41), and vaginal introitus (OR, 1.40) were independent predictors of unsuccessful ring with support pessary fitting. Vaginal length (OR, 0.74/0.60 for ring with support/Gellhorn) and history of POP reconstructive surgery (OR, 2.50/2.58 for ring with support/Gellhorn) were independent predictors of both ring with support and Gellhorn pessary fitting.

Conclusions

Stage IV prolapse, posterior compartment prolapse, large genital hiatus, and wide vaginal introitus were risk factors for unsuccessful fitting of ring pessary with support. Short vaginal length and a history of POP reconstructive surgery were risk factors for unsuccessful fitting of both pessaries.
A Timely Oral Option: Single-Agent Vinorelbine in Desmoid Tumors
Authors: Gennatas Spyridon , Chamberlain Florence , Smrke Alannah , Stewart James , Hayes Andrew , Roden Lorna , Messiou Christina , Kowa Jie-Ying , Estival Anna , Chauhan Dharmisha , Thway Khin , Fisher Cyril , van der Graaf Winette T. A. , Jones Robin L. , Benson Charlotte
Published: September 2020

Introduction

Desmoid tumors (DT) are rare collagen-forming tumors that can exhibit locally aggressive patterns of behavior. The aim of this study was to evaluate the efficacy and safety of treatment of DT with single-agent oral vinorelbine.

Materials and Methods

A retrospective review of patients treated with vinorelbine 90 mg orally on days 1, 8, and 15 of a 28-day cycle from January 2004 to July 2019 was performed. Response was assessed using RECIST version 1.1. Descriptive statistics were employed.

Results

A total of 29 patients were included. Response rate was 20.7% (6/29), and clinical benefit rate (response by RECIST 1.1 and/or clinical symptom improvement) was 65.5% (19/29). No patient experienced grade 3 or above toxicity. Common toxicities were grade 1–2 nausea (14/26, 48.3%), fatigue (9/26, 31.0%), and diarrhea (4/26, 13.8%).

Conclusion

Single-agent oral vinorelbine is an effective, safe, and well-tolerated treatment for DT. It represents a new oral alternative for management of DT.
Penetration Process of a Hydrated Deep Eutectic Solvent Through the Stratum Corneum and its Application as a Protein Penetration Enhancer
Authors: Sakuragi Mina , Maeda Emika , Kusakabe Katsuki
Published: September 2020

The penetration mechanism of choline chloride‐glycerol deep eutectic solvent (DES) through the stratum corneum (SC) as a potential solvent for a novel enhancer of protein penetration into the skin was investigated in a wide and small angle X‐ray diffraction study. We found that DES penetrated through intercellular lipids but not the corneocytes. DES seemed to extract a portion of lipids of the short lamellae in the SC. Hydrated DES with a DES to water weight ratio of 9 to 1 (9DES‐1H2O) showed the strongest interaction with the lipids in the SC compared with water, DES, and hydrated DESs with another weight ratio of DES to water (DES : water=8 : 2). In a skin penetration test with a fluorescently labelled lysozyme, 9DES‐1H2O increased the amount of penetration through the SC by two‐fold compared with HEPES buffer.
Curriculum Reform in The Common Core Era: Evaluating Elementary Math Textbooks Across Six U.S. States
Authors: Blazar David , Heller Blake , Kane Thomas J. , Polikoff Morgan , Staiger Douglas O. , Carrell Scott , Goldhaber Dan , Harris Douglas N. , Hitch Rachel , Holden Kristian L. , Kurlaender Michal
Published: September 2020

Can a school or district improve student achievement simply by switching to a higher‐quality textbook or curriculum? We conducted the first multi‐textbook, multi‐state effort to estimate textbook efficacy following widespread adoption of the Common Core State Standards (CCSS) and associated changes in the textbook market. Pooling textbook adoption and student test score data across six geographically and demographically diverse U.S. states, we found little evidence of differences in average achievement gains for schools using different math textbooks. We found some evidence of greater variation in achievement gains among schools using pre‐CCSS editions, which may have been more varied in their content than post‐CCSS editions because they were written for a broader set of standards. We also found greater variation among schools that had more exposure to a given text. However, these differences were small. Despite considerable interest and attention to textbooks as a low‐cost, “silver bullet” intervention for improving student outcomes, we conclude that the adoption of a new textbook or set of curriculum materials, on its own, is unlikely to achieve this goal.
Quantification by LC–MS/MS of astragaloside IV and isoflavones in Astragali radix can be more accurate by using standard addition
Authors: Kafle Bijay , Baak Jan , Brede Cato
Published: September 2020

Introduction

Astragali radix (AR), the root of Astragalus, is an important medical herb widely used in traditional Chinese medicine. Bioactive components include isoflavones and a unique class of triterpenoid saponins (named astragalosides).

Objectives

Accurate measurement of bioactive components, especially astragaloside IV, is necessary for confirming AR authenticity, quality control and future medical research.

Methodology

Liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) is a suitable technique but suffers from ion suppression effects due to sample matrix. This can be corrected by using isotopic labelled internal standards, but these are not available for many phytochemicals. We explored the use of standard addition to circumvent this issue.

Results

LC–MS/MS and liquid chromatography coupled with ultraviolet (LC‐UV) detection provided linear calibration curves (R2 > 0.99). LC–MS/MS provided superior selectivity and detection limits below 10 ng/mL, which was 2–3 magnitudes lower than LC‐UV detection. Precision and accuracy were overall improved by using LC–MS/MS with diluted sample extracts, resulting in an inter series coefficient of variation (CV) of 12% or less and mean recovery estimates in the 85–115% range. LC–MS/MS quantification by standard addition resulted in significantly higher concentrations of astragaloside IV measured in the samples. Concentrations calculated by standard addition were unaffected by large variation in signal response caused by matrix effects, independent of variation in slope of the standard addition curves.

Conclusion

Sample dilution was helpful but not sufficient for reducing effects of ion suppression. We have shown that LC–MS/MS quantification by standard addition can be a powerful approach for accurate measurement of phytochemicals in the absence of isotopic labelled internal standards.
Using Deep Learning to Extrapolate Protein Expression Measurements
Authors: Barzine Mitra Parissa , Freivalds Karlis , Wright James C. , Opmanis Mārtiņš , Rituma Darta , Ghavidel Fatemeh Zamanzad , Jarnuczak Andrew F. , Celms Edgars , Čerāns Kārlis , Jonassen Inge , Lace Lelde , Vizcaíno Juan Antonio , Choudhary Jyoti Sharma , Brazma Alvis , Viksna Juris
Published: September 2020

Mass spectrometry (MS)‐based quantitative proteomics experiments typically assay a subset of up to 60% of the ≈20 000 human protein coding genes. Computational methods for imputing the missing values using RNA expression data usually allow only for imputations of proteins measured in at least some of the samples. In silico methods for comprehensively estimating abundances across all proteins are still missing.

Here, a novel method is proposed using deep learning to extrapolate the observed protein expression values in label‐free MS experiments to all proteins, leveraging gene functional annotations and RNA measurements as key predictive attributes. This method is tested on four datasets, including human cell lines and human and mouse tissues. This method predicts the protein expression values with average scores between 0.46 and 0.54, which is significantly better than predictions based on correlations using the RNA expression data alone. Moreover, it is demonstrated that the derived models can be “transferred” across experiments and species. For instance, the model derived from human tissues gave a when applied to mouse tissue data. It is concluded that protein abundances generated in label‐free MS experiments can be computationally predicted using functional annotated attributes and can be used to highlight aberrant protein abundance values.
Comparison between Two Methods to Evaluate Function in Postoperative Breast Cancer Survivors
Authors: Back Bruna Baungarten Hugen , Zomkowski Kamilla , de Souza Cunha Natália , Santos Gilmar Moraes , Sacomori Cinara , Sperandio Fabiana Flores
Published: September 2020

Introduction

Treatment for breast cancer can cause adverse effects such as pain and reduced upper limb function which can affect activities of daily living. The Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire is the most used tool for evaluating function in breast cancer survivors. However, some specific aspects have raised discussions about its restricted coverage, which can generate several biases.

Objective

To determine if DASH scores differed when assessed before and after task‐oriented training (TOT) at 3 and 6 months after breast cancer surgery.

Design

Prospective cohort study.

Setting

Institutional study of 22 women assessed at 3 and 6 months after breast cancer surgery.

Main Outcome Measures

The DASH questionnaire and TOT assessment. Two correlation tests were performed: Spearman's correlation between the total score of the two DASH scores (pre‐ and post‐TOT) and the Kendall's tau correlation between each of the items.

Results

There was a moderate and excellent correlation between final DASH scores, pre‐ and post‐TOT, at both 3 and 6 months postoperatively. However, when assessed individually, most of the DASH items were poorly correlated. There was also no agreement between the total DASH scores pre‐ and post‐TOT as assessed by Bland‐Altman plots.

Conclusion

Both the DASH and TOT are considered useful in clinical practice to assess upper limb function, although the use of TOT in some of the DASH items may reduce memory bias and improve skills estimation.
Greater length of stay and hospital charges for severe asthma in children with depression or anxiety
Authors: Munoz Fernando A. , Benton Lauren D. , Kops Samantha A. , Kowalek Katie A. , Seckeler Michael D.
Published: September 2020

Rationale

Asthma is one of the most common chronic disorders of childhood and is associated with significant healthcare utilization and costs. Comorbid psychiatric illnesses, specifically depression and anxiety, are more prevalent in patients with asthma and associated with worse asthma control, more emergency department visits, and increased hospitalization rates.

Objectives

We aimed to compare hospital outcomes and charges for children with severe asthma with and without comorbid depression and anxiety, hypothesizing that those with depression and anxiety would have longer hospitalizations and higher charges.

Methods

Retrospective review of the 2000–2012 Healthcare Cost and Utilization Project's Kids' Inpatient Databases for admissions of patients aged 10–21 years with an ICD‐9 code severe asthma (status asthmaticus or any asthma diagnosis with a procedure code for endotracheal intubation). Depression and Anxiety subgroups were created based on ICD‐9 codes. Data collected included demographics, hospital outcomes and charges and comparisons made between groups.

Results

There were 52,485 admissions for severe asthma: 45,094 (86%) with No Comorbid Psychiatric Illnesses, 1284 (2.4%) with depression, and 1297 (2.5%) with anxiety. Patients with depression or anxiety were older, had longer hospitalizations, and higher hospital charges (p < .001 for all).

Conclusions

Comorbid depression or anxiety is associated with significantly longer hospitalizations and higher charges for children with severe asthma. These findings add to prior reports of worse outcomes for children with asthma and comorbid depression or anxiety and suggest that improved screening for and management of these conditions in children with asthma could improve hospital outcomes and reduce costs.
Archaeal roots of intramembrane aspartyl protease siblings signal peptide peptidase and presenilin
Authors: Raut Priyam , Glass Jennifer B. , Lieberman Raquel L.
Published: September 2020

Signal peptides help newly synthesized proteins reach the cell membrane or be secreted. As part of a biological process key to immune response and surveillance in humans, and associated with diseases, for example, Alzheimer, remnant signal peptides and other transmembrane segments are proteolyzed by the intramembrane aspartyl protease (IAP) enzyme family. Here, we identified IAP orthologs throughout the tree of life. In addition to eukaryotes, IAPs are encoded in metabolically diverse archaea from a wide range of environments. We found three distinct clades of archaeal IAPs: (a) Euryarchaeota (eg, halophilic Halobacteriales, methanogenic Methanosarcinales and Methanomicrobiales, marine Poseidoniales, acidophilic Thermoplasmatales, hyperthermophilic Archaeoglobus spp.), (b) DPANN, and (c) Bathyarchaeota, Crenarchaeota, and Asgard. IAPs were also present in bacterial genomes from uncultivated members of Candidate Phylum Radiation, perhaps due to horizontal gene transfer from DPANN archaeal lineages. Sequence analysis of the catalytic motif YD…GXGD (where X is any amino acid) in IAPs from archaea and bacteria reveals WD in Lokiarchaeota and many residue types in the X position. Gene neighborhood analysis in halophilic archaea shows IAP genes near corrinoid transporters (btuCDF genes). In marine Euryarchaeota, a putative BtuF‐like domain is found in N‐terminus of the IAP gene, suggesting a role for these IAPs in metal ion cofactor or other nutrient scavenging. Interestingly, eukaryotic IAP family members appear to have evolved either from Euryarchaeota or from Asgard archaea. Taken together, our phylogenetic and bioinformatics analysis should prompt experiments to probe the biological roles of IAPs in prokaryotic secretomes.