bluuebunny/crossref_metadata_2025 huggingface dataset:
Mobility, Skepticism, and Counter-storytelling in African American Travel Writing: Carl Rowan'sSouth of Freedom
Authors: TOTTEN GARY
Published: July 2020

InSouth of Freedom(1952), Carl Rowan frames his travels through an investigation of the US South in terms of his doubts about cultural change, his safety, and whites’ and blacks’ willingness to participate in racial reform, among other things. His skepticism about improvements in race relations and his critique of the country's inadequate progress toward such goals inform his examination of various states of freedom and unfreedom existing in the United States. Rowan's narrative and specific descriptions of his and others’ mobility operate as instances of counter-storytelling that incorporate such skepticism and critique. Ultimately, his theorizing of modes of resistance to institutionalized racism through individual action serves as a model for understanding African American travel writing and mobility more generally.
Phonetic documentation in three collections: Topics and evolution
Authors: Whalen D. H. , DiCanio Christian , Dockum Rikker
Published: July 2020

Phonetic aspects of many languages have been documented, though the breadth and focus of such documentation varies substantially. In this survey, phonetic aspects (here called ‘categories’) that are typically reported were assessed in three English-language collections – the Illustrations of the IPA from theJournal of the International Phonetic Association, articles from theJournal of Phonetics, and papers from the Ladefoged/Maddieson Sounds of the World’s Languages (SOWL) documentation project. Categories were defined for consonants (e.g. Voice Onset Time (VOT) and frication spectrum; 10 in total), vowels (e.g. formants and duration; 7 in total) and suprasegmentals (e.g. stress and distinctive vowel length, 6 in total). The Illustrations, due to their brevity, had, on average, limited coverage of the selected categories (12% of the 23 categories).Journal of Phoneticsarticles were typically theoretically motivated, but 64 had sufficient measurements to count as phonetic documentation; these also covered 12% of the categories. The SOWL studies, designed to cover as much of the phonetic structure as feasible in an article-length treatment, achieved 41% coverage on average. Four book-length studies were also examined, with an average of 49% coverage. Phonetic properties of many language families have been studied, though Indo-European is still disproportionately represented. Physiological measures were excluded as being less common, and perceptual measures were excluded as being typically more theoretical. This preliminary study indicates that certain acoustic properties of languages are typically measured and may be considered as an impetus for later, fuller coverage, but broader consensus on the categories is needed. Current and future documentation efforts would benefit these considerations being addressed.
Anomalous fluctuations and selective extinction in primordial replicators: a ‘struggle for life’ at the origin of biological homochirality
Authors: Longo Savino , Chincoli Miriana Carmela , Micca Longo Gaia
Published: July 2020

The prevalent presence of a single chiral variant of molecules in live organisms is one of the most distinctive signs of life as a global phenomenon. One of the greatest ambitions of biochemistry and astrobiology is to provide an explanation of this predominance. Several mechanisms were proposed in the past, from the propagation of chirality from a homo-chiral substrate to the amplification of effects associated with electro-weak interactions. Here, a different scenario is proposed: anomalous fluctuations associated with a self-replication scenario can lead to the selective extinction of primordial organisms using one of two enantiomers as an enzyme. These fluctuations arise spontaneously under very general conditions. The idea is based on three key points: (a) the simulation of early biological processes as a ‘board game’; (b) the presence of large fluctuations during an autocatalytic process; (c) the presence of a limited source of chemical energy, inducing a form of competition in a primordial replicator population. In order to demonstrate this mechanism, a computational model is developed, describing the ‘struggle for life’ of two different kinds of primordial replicators on a ‘chessboard’ with periodic boundary conditions; each replicator employs enzymes of different chirality on a non-chiral substrate, thereby with no selective advantage. The replication occurs randomly and with a fixed probability, providing that a sufficient amount of chemical energy is locally available. For the first time, our model includes the local balance of chemical energy in a molecular form on the substrate. The correlation between the chemical energy and the local populations is shown. Results clearly show that strong fluctuations in the number of individuals of each species and subsequent selective extinction events of one of the two species are observed. These studies may contribute to shed light on the most mysterious phase transition that occurred during the biochemical evolution of our planet.
Service evaluation of a sole-session psychoeducational intervention to improve caregivers’ key illness beliefs after first episode psychosis (FEP)
Authors: Hazell Cassie M. , Lyons Natasha , Onwumere Juliana , Schulz Joerg , Glover Naomi , Whittaker Sarah , Chu Man Lai , Floyd Caroline , Brown Lucy , James Gareth , Afshardazegan Roya , Seneviratne Saal , Rahim Shireen , Souray Jonathan , Raune David
Published: July 2020

Carers of people experiencing a first episode of psychosis are at an increased risk of developing their own physical and mental health problems. Psychoeducation has been found to improve carer wellbeing and reduce distress. However, few psychoeducation interventions have considered the resource constraints on mental health services and the impact that these can have on the implementation of any such interventions. The present service evaluation aimed to evaluate an abbreviated version (sole session) of a previously tested psychoeducation intervention (three sessions) that targets less adaptive illness beliefs (n = 17). Pre–post effect sizes reveal that all of the carers’ illness beliefs changed in the desired direction, with four out of the 10 illness beliefs associated with large to moderate improvements. When compared with the outcomes obtained in our evaluation of the more intensive, three-session version of the intervention, the between-group effects largely favoured the three-session version but were mostly small. Moderate to large effects in favour of the three-session version were found for two of the 10 illness beliefs. These findings support the further investigation of the sole session psychoeducation intervention as part of a randomised controlled trial.

Key learning aims

(1)

To evaluate the impact of a sole-session psychoeducation intervention on illness beliefs.

(2)

To compare the outcomes of the sole-session psychoeducation intervention to the previous, more intensive (three-session) version of the same intervention.

(3)

To consider the value of research approaches to evaluating psychoeducation interventions for carers of people with psychosis.
The Effectiveness of Interventions Aimed at Improving Well-Being and Resilience to Stress in First Responders
Authors: Wild Jennifer , El-Salahi Shama , Esposti Michelle Degli
Published: July 2020

Abstract. First responders are routinely exposed to traumatic critical incidents, placing them at higher risk for developing stress-related psychopathology and associated health problems than the general population. Interventions which could improve resilience to stress may help to protect the health of this high risk population. We systematically reviewed such interventions for first responders to determine which ones work and why. We searched the Cochrane and Campbell Collaboration Library, EMBASE, IBSS, Medline, PILOTS, PubMed, PsycINFO, and SCOPUS from January 1, 1980 to June 28, 2018 for randomized and quasi-randomized controlled studies aiming to improve well-being, resilience, or stress management for police, ambulance, fire, or search and rescue workers using non-pharmacological interventions. Data were extracted from published reports and obtained from authors. Within- and between-group effect sizes were calculated for mental and physical health outcomes. Risk of bias was assessed using the Cochrane Collaboration’s Risk of Bias Tool. The initial search identified 3,816 studies, 13 of which were eligible for analysis ( n = 634 cases, n = 628 controls). Six studies demonstrated intervention-related improvements. However, risk of bias was mostly unclear or high. Within-group intervention effect sizes ranged from −0.82 (95% CI [−1.48, −0.17]) to 2.71 [1.99, 3.42] and between-group intervention effect sizes ranged from −0.73 [−1.25, −0.21] to 1.47 [0.94, 2.01], depending on the outcome. Largest effects were seen for interventions that targeted modifiable risk factors for trauma-related psychiatric disorders. Targeting modifiable predictors of trauma-related psychiatric disorders through training may protect the health of first responders who routinely face trauma in their line of work.
A Global Classification of Astronomical Tide Asymmetry and Periodicity Using Statistical and Cluster Analysis
Authors: Núñez P. , Castanedo S. , Medina R.
Published: July 2020

Tidal asymmetry plays a key role in the behavior of estuaries. Positive and negative asymmetries are associated with flood‐ and ebb‐dominated estuaries, respectively. Asymmetry arises from both the interaction among the main tidal constituents and the harmonics generated when tide propagates in shallow waters. Most previous research focuses on the deformation of the tide within estuaries; however, ocean tide may show asymmetry at the estuary entrance, which implies that the boundary condition is already deformed. This fact has important implications for tide propagation, estuarine transport processes, and flow exchanges between estuaries and open oceans. In this study, the global astronomical tide is classified according to its asymmetry and periodicity. The objective is to provide a guiding framework of representative astronomical tide types (ATtypes) on a worldwide scale to be used as a reference for further research on the transport of substances in estuaries. The applied methodology is based on the use of the TPXO9‐atlas global barotropic tidal solution and detailed statistical analysis. Probability density functions of the tidal elevation time derivative and the tidal form factor were extracted from TPXO9‐atlas with a spatial resolution ranging from 1/6° to 1/30°. The K‐means algorithm was applied to these parameters, and 25 representativeATtypeswere identified. The classification was validated with 757 worldwide tide gauge records. The results show that 11.3% of coastal areas show negative asymmetries, 11.3% positive asymmetries, while symmetric tides dominate 77.4% of coastal areas. In these areas, estuaries can show asymmetries exclusively dependent on overtides and compound tides generated during inland propagation without being externally conditioned.
Effect of Small Tidal Fluctuations on the Stability and Equilibrium Configurations of Bifurcations
Authors: Ragno Niccolò , Tambroni Nicoletta , Bolla Pittaluga Michele
Published: July 2020

Deltas are fascinating landforms subject to fluvial and marine forcing. Bifurcations are common features in deltas, governing the distribution of water and sediment fluxes among the distributary channel network. Recently, it has been observed that tide‐influenced deltas tend to display less numerous but more stable branches in comparison to their riverine counterparts. River bifurcations subject to unidirectional flow have been widely studied in the last decades. In contrast, the acting physical mechanisms and factors controlling the stability of bifurcations in tide‐influenced deltas are still not well understood, and a theoretical framework is still lacking. In order to fill this gap and understand how the stability and evolution of bifurcations in distributary deltaic systems could be affected by the tides, we investigate, through an analytical model, the equilibrium configurations and stability of tidal bifurcations under the hypothesis of small monochromatic tidal oscillations. In particular, we build on previous works on river bifurcations, incorporating the solution for the equilibrium of a single‐river‐dominated estuary. We find that higher tidal amplitudes and a closer proximity of the junction node to the sea tend to hamper the development of unbalanced solutions, reducing the asymmetries in water and sediment fluxes between branches. This stabilizing effect exerted by the tidal action is associated with the erosive character of the tidal currents that promotes channel deepening and increases the capacity of the system to keep morphodynamically active both bifurcates in comparison with the purely fluvial case. Preliminary field observations of natural deltas corroborate our findings.
Translation of the shortened dental arch research into clinical practice: a stakeholder mapping approach
Authors: Khan Saadika B.
Published: July 2020

Aim

To identify key participants that can ensure implementation of the SDA or PRDA as a prosthodontic management option using a stakeholder mapping approach.

Methods

A stakeholder mapping approach is employed which is a strategic method to identify, rate the importance of input and the influence, highlighting how clinical implementation can be ensured. A stakeholder map was used as the research tool. Stakeholders were classified according to their level of influence in either assisting with change or obstructing progress as well as the impact of their input within the dental organization and the broader South African environment.

Results

Several stakeholders were identified and were classified in two ways: Primary or secondary and according to their affiliation with the organization where change needs to occur. Initially, a lecture on the shortened dental arch was included in 4th year of undergraduate study, after consultation with the head of the department. This was abandoned as students misunderstood the use of the concept related to clinical requirements; thus, the location of where this concept must be taught, was reconsidered. The role of other key stakeholders that could effect change was also highlighted with this approach.

Conclusion

This strategic analysis allowed identification of key stakeholders and their roles that can assist with implementation of the SDA or PRDA, some of whom should be addressed further to ensure alignment of practices to health policies.

Key points

Knowledge translation consists of multiple stages from design to implementation which includes diffusion, dissemination (such as publishing) and implementation of evidence into clinical practice (application of concepts or procedures to improve patient care).

Only quality research, as stipulated on the evidence pyramid, can be used to change curricula and clinical practices.

The strategic approach with stakeholder mapping allows identification of key stakeholders in prosthodontics (knowledge brokers or communities of practice) that have the interest and influence to change curricula and clinical practice; including a combined approach with researchers which may enable easier application of quality care to patients.
Neonatal genetics of gene expression reveal potential origins of autoimmune and allergic disease risk
Authors: Huang Qin Qin , Tang Howard H. F. , Teo Shu Mei , Mok Danny , Ritchie Scott C. , Nath Artika P. , Brozynska Marta , Salim Agus , Bakshi Andrew , Holt Barbara J. , Khor Chiea Chuen , Sly Peter D. , Holt Patrick G. , Holt Kathryn E. , Inouye Michael
Published: July 2020

Chronic immune-mediated diseases of adulthood often originate in early childhood. To investigate genetic associations between neonatal immunity and disease, we map expression quantitative trait loci (eQTLs) in resting myeloid cells and CD4+T cells from cord blood samples, as well as in response to lipopolysaccharide (LPS) or phytohemagglutinin (PHA) stimulation, respectively.Cis-eQTLs are largely specific to cell type or stimulation, and 31% and 52% of genes withcis-eQTLs have response eQTLs (reQTLs) in myeloid cells and T cells, respectively. We identifiedcisregulatory factors acting as mediators oftranseffects. There is extensive colocalisation between condition-specific neonatalcis-eQTLs and variants associated with immune-mediated diseases, in particularCTSHhad widespread colocalisation across diseases. Mendelian randomisation shows causal neonatal gene expression effects on disease risk forBTN3A2,HLA-Cand others. Our study elucidates the genetics of gene expression in neonatal immune cells, and aetiological origins of autoimmune and allergic diseases.
On the natural spatio-temporal heterogeneity of South Pacific nitrous oxide
Authors: Babbin Andrew R. , Boles Elisabeth L. , Mühle Jens , Weiss Ray F.
Published: July 2020

Nitrous oxide (N2O) is a powerful greenhouse gas and ozone depleting substance, but its natural sources, especially marine emissions, are poorly constrained. Localized high concentrations have been observed in the oxygen minimum zones (OMZs) of the tropical Pacific but the impacts of El Niño cycles on this key source region are unknown. Here we show atmospheric monitoring station measurements in Samoa combined with atmospheric back-trajectories provide novel information on N2O variability across the South Pacific. Remarkable elevations in Samoan concentrations are obtained in air parcels that pass over the OMZ. The data further reveal that average concentrations of these OMZ air parcels are augmented during La Niña and decrease sharply during El Niño. The observed natural spatial heterogeneities and temporal dynamics in marine N2O emissions can confound attempts to develop future projections of this climatically active gas as low oxygen zones are predicted to expand and El Niño cycles change.
Mechanisms of microtubule dynamics and force generation examined with computational modeling and electron cryotomography
Authors: Gudimchuk Nikita B. , Ulyanov Evgeni V. , O’Toole Eileen , Page Cynthia L. , Vinogradov Dmitrii S. , Morgan Garry , Li Gabriella , Moore Jeffrey K. , Szczesna Ewa , Roll-Mecak Antonina , Ataullakhanov Fazoil I. , Richard McIntosh J.
Published: July 2020

Microtubules are dynamic tubulin polymers responsible for many cellular processes, including the capture and segregation of chromosomes during mitosis. In contrast to textbook models of tubulin self-assembly, we have recently demonstrated that microtubules elongate by addition of bent guanosine triphosphate tubulin to the tips of curving protofilaments. Here we explore this mechanism of microtubule growth using Brownian dynamics modeling and electron cryotomography. The previously described flaring shapes of growing microtubule tips are remarkably consistent under various assembly conditions, including different tubulin concentrations, the presence or absence of a polymerization catalyst or tubulin-binding drugs. Simulations indicate that development of substantial forces during microtubule growth and shortening requires a high activation energy barrier in lateral tubulin-tubulin interactions. Modeling offers a mechanism to explain kinetochore coupling to growing microtubule tips under assisting force, and it predicts a load-dependent acceleration of microtubule assembly, providing a role for the flared morphology of growing microtubule ends.
Author Correction: Mutant p53 drives clonal hematopoiesis through modulating epigenetic pathway
Authors: Chen Sisi , Wang Qiang , Yu Hao , Capitano Maegan L. , Vemula Sasidhar , Nabinger Sarah C. , Gao Rui , Yao Chonghua , Kobayashi Michihiro , Geng Zhuangzhuang , Fahey Aidan , Henley Danielle , Liu Stephen Z. , Barajas Sergio , Cai Wenjie , Wolf Eric R. , Ramdas Baskar , Cai Zhigang , Gao Hongyu , Luo Na , Sun Yang , Wong Terrence N. , Link Daniel C. , Liu Yunlong , Boswell H. Scott , Mayo Lindsey D. , Huang Gang , Kapur Reuben , Yoder Mervin C. , Broxmeyer Hal E. , Gao Zhonghua , Liu Yan
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Plasma levels of DPP4 activity and sDPP4 are dissociated from inflammation in mice and humans
Authors: Baggio Laurie L. , Varin Elodie M. , Koehler Jacqueline A. , Cao Xiemin , Lokhnygina Yuliya , Stevens Susanna R. , Holman Rury R. , Drucker Daniel J.
Published: July 2020

Dipeptidyl peptidase-4 (DPP4) modulates inflammation by enzymatic cleavage of immunoregulatory peptides and through its soluble form (sDPP4) that directly engages immune cells. Here we examine whether reduction of DPP4 activity alters inflammation. Prolonged DPP4 inhibition increases plasma levels of sDPP4, and induces sDPP4 expression in lymphocyte-enriched organs in mice. Bone marrow transplantation experiments identify hematopoietic cells as the predominant source of plasma sDPP4 following catalytic DPP4 inhibition. Surprisingly, systemic DPP4 inhibition increases plasma levels of inflammatory markers in regular chow-fed but not in high fat-fed mice. Plasma levels of sDPP4 and biomarkers of inflammation are lower in metformin-treated subjects with type 2 diabetes (T2D) and cardiovascular disease, yet exhibit considerable inter-individual variation. Sitagliptin therapy for 12 months reduces DPP4 activity yet does not increase markers of inflammation or levels of sDPP4. Collectively our findings dissociate levels of DPP4 enzyme activity, sDPP4 and biomarkers of inflammation in mice and humans.
Origin and function of the yolk sac in primate embryogenesis
Authors: Ross Connor , Boroviak Thorsten E.
Published: July 2020

Human embryogenesis is hallmarked by two phases of yolk sac development. The primate hypoblast gives rise to a transient primary yolk sac, which is rapidly superseded by a secondary yolk sac during gastrulation. Moreover, primate embryos form extraembryonic mesoderm prior to gastrulation, in contrast to mouse. The function of the primary yolk sac and the origin of extraembryonic mesoderm remain unclear. Here, we hypothesise that the hypoblast-derived primary yolk sac serves as a source for early extraembryonic mesoderm, which is supplemented with mesoderm from the gastrulating embryo. We discuss the intricate relationship between the yolk sac and the primate embryo and highlight the pivotal role of the yolk sac as a multifunctional hub for haematopoiesis, germ cell development and nutritional supply.
3D-3D topotactic transformation in aluminophosphate molecular sieves and its implication in new zeolite structure generation
Authors: Huang Zhehao , Seo Seungwan , Shin Jiho , Wang Bin , Bell Robert G. , Hong Suk Bong , Zou Xiaodong
Published: July 2020

Zeolites have unique pore structures of molecular dimensions and tunable compositions, making them ideal for shape selective catalysis and separation. However, targeted synthesis of zeolites with new pore structures and compositions remains a key challenge. Here, we propose an approach based on a unique 3D-3D topotactic transformation, which takes advantage of weak bonding in zeolites. This is inspired by the structure transformation of PST-5, a new aluminophosphate molecular sieve, to PST-6 by calcination. The structure of nano-sized PST-5 crystals is determined by 3D electron diffraction. We find that the 3D-3D topotactic transformation involves two types of building units where penta- or hexa-coordinated Al is present. We apply this approach to several other zeolite systems and predict a series of new zeolite structures that would be synthetically feasible. This method provides a concept for the synthesis of targeted zeolites, especially those which may not be feasible by conventional methods.
Higher-order quantum spin Hall effect in a photonic crystal
Authors: Xie Biye , Su Guangxu , Wang Hong-Fei , Liu Feng , Hu Lumang , Yu Si-Yuan , Zhan Peng , Lu Ming-Hui , Wang Zhenlin , Chen Yan-Feng
Published: July 2020

The quantum spin Hall effect lays the foundation for the topologically protected manipulation of waves, but is restricted to one-dimensional-lower boundaries of systems and hence limits the diversity and integration of topological photonic devices. Recently, the conventional bulk-boundary correspondence of band topology has been extended to higher-order cases that enable explorations of topological states with codimensions larger than one such as hinge and corner states. Here, we demonstrate a higher-order quantum spin Hall effect in a two-dimensional photonic crystal. Owing to the non-trivial higher-order topology and the pseudospin-pseudospin coupling, we observe a directional localization of photons at corners with opposite pseudospin polarizations through pseudospin-momentum-locked edge waves, resembling the quantum spin Hall effect in a higher-order manner. Our work inspires an unprecedented route to transport and trap spinful waves, supporting potential applications in topological photonic devices such as spinful topological lasers and chiral quantum emitters.
Author Correction: Fire deficit increases wildfire risk for many communities in the Canadian boreal forest
Authors: Parisien Marc-André , Barber Quinn E. , Hirsch Kelvin G. , Stockdale Christopher A. , Erni Sandy , Wang Xianli , Arseneault Dominique , Parks Sean A.
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Study of Kyasanur forest disease viremia, antibody kinetics, and virus infection in target organs of Macaca radiata
Authors: Patil Dilip R. , Yadav Pragya D. , Shete Anita , Chaubal Gouri , Mohandas Sreelekshmy , Sahay Rima R. , Jain Rajlaxmi , Mote Chandrashekhar , Kumar Sandeep , Kaushal Himanshu , Kore Pravin , Patil Savita , Majumdar Triparna , Fulari Siddharam , Suryawanshi Annasaheb , Kadam Manoj , Pardeshi Prachi G. , Lakra Rajen , Sarkale Prasad , Mourya Devendra T.
Published: July 2020

The present manuscript deals with experimental infections of bonnet macaques (Macaca radiata) to study disease progression for better insights into the Kyasanur Forest Disease (KFD) pathogenesis and transmission. Experimentally, 10 monkeys were inoculated with KFD virus (KFDV) (high or low dose) and were regularly monitored and sampled for various body fluids and tissues at preset time points. We found that only 2 out of the 10 animals showed marked clinical signs becoming moribund, both in the low dose group, even though viremia, virus shedding in the secretions and excretions were evident in all inoculated monkeys. Anti-KFDV immunoglobulin (Ig)M antibody response was observed around a week after inoculation and anti-KFDV IgG antibody response after two weeks. Anaemia, leucopenia, thrombocytopenia, monocytosis, increase in average clotting time, and reduction in the serum protein levels were evident. The virus could be re-isolated from the skin during the viremic period. The persistence of viral RNA in the gastrointestinal tract and lymph nodes was seen up to 53 and 81 days respectively. Neuro-invasion was observed only in moribund macaques. Re-challenge with the virus after 21 days of initial inoculation in a monkey did not result in virus shedding or immune response boosting.
Variability of a natural hydrocarbon seep and its connection to the ocean surface
Authors: Razaz Mahdi , Di Iorio Daniela , Wang Binbin , Daneshgar Asl Samira , Thurnherr Andreas M.
Published: July 2020

Natural hydrocarbon seeps are ubiquitous along continental margins. Despite their significance, we lack a basic understanding of the long-term temporal variability of seep dynamics, including bubble size, rise velocity, composition, and upwelling and entrainment processes. The shortcoming makes it difficult to constrain the global estimates of oil and gas entering the marine environment. Here we report on a multi-method approach based on optical, acoustic, satellite remote sensing, and simulations, to connect the characteristics of a hydrocarbon seep in the Gulf of Mexico to its footprint on the sea surface. Using an in-situ camera, bubble dynamics at the source were measured every 6 h over 153 days and the integrated total hydrocarbon release volume was estimated as 53 m3. The vertical velocity was acoustically measured at 20 m above bed (mab) and found to be approximately 40% less than the dispersed-phase at the source, indicating that the measured values are reflecting the plume continuous-phase flow. Numerical simulations predict that the oily bubbles with diameters larger than 8 mm reach the surface with a small footprint, i.e. forming an oil slick origin, deflection of which with wind and surface current leads to the formation of an oil slick on the surface. Nineteen SAR images are used to estimate the oil seepage rate from GC600 for 2017 giving an average discharge of 14.4 cm3/s.
Paraffin-embedding for large volume bio-tissue
Authors: Zhanmu Ouyang , Yang Xiaoying , Gong Hui , Li Xiangning
Published: July 2020

Acquiring ultrahigh-resolution three-dimensional images of large-volume tissues non-human primate tissues was an enormous challenge. Given the preservation of structure and excellent sectioning property, formalin-fixed paraffin-embedding method had an enormous potential for three-dimensional reconstruction of fine structures, based on the very thin histological sections and optical images. However, maintaining the structure uniformly in large-volume tissues was difficult during the complex processes. In this study, we presented a detailed protocol for the whole mouse, rat, rabbit brains, and even for the macaque hemisphere. The entire protocol took about 2–30 days to complete for a large sample, including fixation, dehydration, clearing, wax immersion and embedding. In addition, it could be applied to other species and organs, while the embedding processes depended on the size and the type of organs. This method had wide applicability to serve as a baseline for further technique development.
Comparative clinical and genomic analysis of neurofibromatosis type 2-associated cranial and spinal meningiomas
Authors: Pemov Alexander , Dewan Ramita , Hansen Nancy F. , Chandrasekharappa Settara C. , Ray-Chaudhury Abhik , Jones Kristine , Luo Wen , Heiss John D. , Mullikin James C. , Chittiboina Prashant , Stewart Douglas R. , Asthagiri Ashok R.
Published: July 2020

Neurofibromatosis type 2 (NF2) is an autosomal dominant Mendelian tumor predisposition disorder caused by germline pathogenic variants in the tumor suppressor NF2. Meningiomas are the second most common neoplasm in NF2, often occurring in multiple intracranial and spinal locations within the same patient. In this prospective longitudinal study, we assessed volumes and growth rates of ten spinal and ten cranial benign meningiomas in seven NF2 patients that concluded with surgical resection and performed whole-exome sequencing and copy-number variant (CNV) analysis of the tumors. Our comparison of the volume and the growth rate of NF2-associated spinal and cranial meningiomas point to the differences in timing of tumor initiation and/or to the differences in tumor progression (e.g., non-linear, saltatory growth) at these two anatomical locations. Genomic investigation of these tumors revealed that somatic inactivation of NF2 is the principal and perhaps the only driver of tumor initiation; and that tumor progression likely occurs via accumulation of CNVs, rather than point mutations. Results of this study contribute to a better understanding of NF2-associated meningiomas clinical behavior and their genetic underpinnings.
Neuronal correlates of spider phobia in a combined fNIRS-EEG study
Authors: Rosenbaum David , Leehr Elisabeth J. , Kroczek Agnes , Rubel Julian A. , Int-Veen Isabell , Deutsch Kira , Maier Moritz J. , Hudak Justin , Fallgatter Andreas J. , Ehlis Ann-Christine
Published: July 2020

Specific phobia is associated with aberrant brain activation in confrontation paradigms with phobic stimuli. In previous EEG research enhanced event-related potentials (ERPs) in the late-positive potential (LPP) window have been observed. Further, studies with functional near-infrared spectroscopy (fNIRS) and fMRI suggest that spider phobia is associated with enhanced activation within cortical and subcortical areas. In the current study we investigated the neuronal correlates of spider phobia in a combined fNIRS–EEG study. To this end, 37 spider phobic patients (PP) and 32 healthy controls (HC) underwent a symptom provocation paradigm during which subjects watched video clips of spiders and domestic animals (confrontation phase) after being primed on the content of the video (anticipation phase). Simultaneously, fNIRS, EEG, electromyography (EMG), electrocardiography and behavioral measures were assessed. Results showed increased LPP amplitudes, increased hemodynamic responses in the cognitive control network, and increased EMG activity and heart rate during spider conditions in PP in comparison to HC. Furthermore, in behavioral ratings PP showed higher emotional distress and avoidance. Behavioral ratings, fNIRS and EEG data showed positive correlations on a between-subject as well as on a within-subject level. Our results merge the existing data on neurophysiological correlates of phobic stimulus processing in hemodynamic and electrophysiological research and extend those of static visual material (pictures) to dynamic visual material (videos).
Federated learning in medicine: facilitating multi-institutional collaborations without sharing patient data
Authors: Sheller Micah J. , Edwards Brandon , Reina G. Anthony , Martin Jason , Pati Sarthak , Kotrotsou Aikaterini , Milchenko Mikhail , Xu Weilin , Marcus Daniel , Colen Rivka R. , Bakas Spyridon
Published: July 2020

Several studies underscore the potential of deep learning in identifying complex patterns, leading to diagnostic and prognostic biomarkers. Identifying sufficiently large and diverse datasets, required for training, is a significant challenge in medicine and can rarely be found in individual institutions. Multi-institutional collaborations based on centrally-shared patient data face privacy and ownership challenges. Federated learning is a novel paradigm for data-private multi-institutional collaborations, where model-learning leverages all available data without sharing data between institutions, by distributing the model-training to the data-owners and aggregating their results. We show that federated learning among 10 institutions results in models reaching 99% of the model quality achieved with centralized data, and evaluate generalizability on data from institutions outside the federation. We further investigate the effects of data distribution across collaborating institutions on model quality and learning patterns, indicating that increased access to data through data private multi-institutional collaborations can benefit model quality more than the errors introduced by the collaborative method. Finally, we compare with other collaborative-learning approaches demonstrating the superiority of federated learning, and discuss practical implementation considerations. Clinical adoption of federated learning is expected to lead to models trained on datasets of unprecedented size, hence have a catalytic impact towards precision/personalized medicine.
β1 integrin, ILK and mTOR regulate collagen synthesis in mechanically loaded tendon cells
Authors: Mousavizadeh Rouhollah , Hojabrpour Payman , Eltit Felipe , McDonald Paul C. , Dedhar Shoukat , McCormack Robert G. , Duronio Vincent , Jafarnejad Seyed Mehdi , Scott Alex
Published: July 2020

Tendons are specialized tissues composed primarily of load-responsive fibroblasts (tenocytes) embedded in a collagen-rich extracellular matrix. Habitual mechanical loading or targeted exercise causes tendon cells to increase the stiffness of the extracellular matrix; this adaptation may occur in part through collagen synthesis or remodeling. Integrins are likely to play an important role in transmitting mechanical stimuli from the extracellular matrix to tendon cells, thereby triggering cell signaling pathways which lead to adaptive regulation of mRNA translation and protein synthesis. In this study, we discovered that mechanical stimulation of integrin β1 leads to the phosphorylation of AKT, an event which required the presence of integrin-linked kinase (ILK). Repetitive stretching of tendon cells activates the AKT and mTOR pathways, which in turn regulates mRNA translation and collagen expression. These results support a model in which integrins are an upstream component of the mechanosensory cellular apparatus, regulating fundamental tendon cell functions relevant to exercise-induced adaptation and mechanotherapy.
An unbiased stereological method for corneal confocal microscopy in patients with diabetic polyneuropathy
Authors: Schaldemose Ellen L. , Hammer Rasmus E. , Ferdousi Maryam , Malik Rayaz A. , Nyengaard Jens R. , Karlsson Páll
Published: July 2020

Corneal confocal microscopy (CCM) derived corneal nerve measures are lower in diabetic sensorimotor polyneuropathy (DSPN). There are, however, methodological challenges in relation to adequate and unbiased sampling of images with objective corneal nerve quantification. Here we compare a new sampling method and adjusted area calculation with established methods of corneal nerve quantification in patients with and without DSPN and healthy controls. CCM images from 26 control subjects and 62 patients with type 1 diabetes with (n = 17) and without (n = 45) DSPN were analyzed. The images were randomly selected and corneal nerve fiber length (CNFL), corneal nerve fiber branch density (CNBD) and corneal nerve fiber density (CNFD) were determined in both a manual and automated manner. The new method generated 8–40% larger corneal nerve parameters compared to the standard procedure (p < 0.05). CNFL was significantly reduced using the new method for both manual and automated analysis; whilst CNFD and CNBD were significantly reduced using the automated method in both diabetic groups compared with controls. The new, objective method showed a reduction in corneal nerve parameters in diabetic patients with and without DSPN. We recommend using a randomized sampling method and area-dependent analysis to enable objective unbiased corneal nerve quantification.
Learning to see the Ebbinghaus illusion in the periphery reveals a top-down stabilization of size perception across the visual field
Authors: Eymond Cécile , Seidel Malkinson Tal , Naccache Lionel
Published: July 2020

Our conscious visual perception relies on predictive signals, notably in the periphery where sensory uncertainty is high. We investigated how such signals could support perceptual stability of objects’ size across the visual field. When attended carefully, the same object appears slightly smaller in the periphery compared to the fovea. Could this perceptual difference be encoded as a strong prior to predict the peripheral perceived size relative to the fovea? Recent studies emphasized the role of foveal information in defining peripheral size percepts. However, they could not disentangle bottom-up from top-down mechanisms. Here, we revealed a pure top-down contribution to the perceptual size difference between periphery and fovea. First, we discovered a novel Ebbinghaus illusion effect, inducing a typical reduction of foveal perceived size, but a reversed increase effect in the periphery. The resulting illusory size percept was similar at both locations, deviating from the classic perceptual difference. Then through an updating process of successive peripheral-foveal viewing, the unusual peripheral perceived size decreased. The classic perceptual eccentricity difference was restored and the peripheral illusion effect changed into a fovea-like reduction. Therefore, we report the existence of a prior that actively shapes peripheral size perception and stabilizes it relative to the fovea.
Leprosy piRnome: exploring new possibilities for an old disease
Authors: Pinto Pablo , da Silva Moisés Batista , Moreira Fabiano Cordeiro , Bouth Raquel Carvalho , Gobbo Angélica Rita , Sandoval Tatiana Vinasco , Ribeiro-dos-Santos André Mauricio , Vidal Amanda Ferreira , Barreto Josafá Gonçalves , Santos Sidney , Spencer John Stewart , Salgado Claudio Guedes , Ribeiro-dos-Santos Ândrea
Published: July 2020

Leprosy, which is caused by the human pathogen Mycobacterium leprae, causes nerve damage, deformity and disability in over 200,000 people every year. Because of the long doubling time of M. leprae (13 days) and the delayed onset of detectable symptoms, which is estimated to be approximately 3–7 years after infection, there is always a large percentage of subclinically infected individuals in the population who will eventually develop the disease, mainly in endemic countries. piRNAs comprise the largest group of small noncoding RNAs found in humans, and they are distinct from microRNAs (miRNAs) and small interfering RNAs (siRNAs). piRNAs function in transposon silencing, epigenetic regulation, and germline development. The functional role of piRNAs and their associated PIWI proteins have started to emerge in the development of human cancers and viral infections, but their relevance to bacterial diseases has not been investigated. The present study reports the piRNome of human skin, revealing that all but one of the piRNAs examined are downregulated in leprosy skin lesions. Considering that one of the best characterized functions of piRNAs in humans is posttranscriptional mRNA silencing, their functions are similar to what we have described for miRNAs, including acting on apoptosis, M. leprae recognition and engulfment, Schwann cell (SC) demyelination, epithelial–mesenchymal transition (EMT), loss of sensation and neuropathic pain. In addition to new findings on leprosy physiopathology, the discovery of relevant piRNAs involved in disease processes in human skin may provide new clues for therapeutic targets, specifically to control nerve damage, a prominent feature of leprosy that has no currently available pharmaceutical treatment.
Single-cell mass cytometry on peripheral blood identifies immune cell subsets associated with primary biliary cholangitis
Authors: Jang Jin Sung , Juran Brian D. , Cunningham Kevin Y. , Gupta Vinod K. , Son Young Min , Yang Ju Dong , Ali Ahmad H. , Enninga Elizabeth Ann L. , Sung Jaeyun , Lazaridis Konstantinos N.
Published: July 2020

The relationship between primary biliary cholangitis (PBC), a chronic cholestatic autoimmune liver disease, and the peripheral immune system remains to be fully understood. Herein, we performed the first mass cytometry (CyTOF)-based, immunophenotyping analysis of the peripheral immune system in PBC at single-cell resolution. CyTOF was performed on peripheral blood mononuclear cells (PBMCs) from PBC patients (n = 33) and age-/sex-matched healthy controls (n = 33) to obtain immune cell abundance and marker expression profiles. Hierarchical clustering methods were applied to identify immune cell types and subsets significantly associated with PBC. Subsets of gamma-delta T cells (CD3+TCRgd+), CD8+T cells (CD3+CD8+CD161+PD1+), and memory B cells (CD3−CD19+CD20+CD24+CD27+) were found to have lower abundance in PBC than in control. In contrast, higher abundance of subsets of monocytes and naïve B cells were observed in PBC compared to control. Furthermore, several naïve B cell (CD3−CD19+CD20+CD24−CD27−) subsets were significantly higher in PBC patients with cirrhosis (indicative of late-stage disease) than in those without cirrhosis. Alternatively, subsets of memory B cells were lower in abundance in cirrhotic relative to non-cirrhotic PBC patients. Future immunophenotyping investigations could lead to better understanding of PBC pathogenesis and progression, and also to the discovery of novel biomarkers and treatment strategies.
Pessimism is associated with greater all-cause and cardiovascular mortality, but optimism is not protective
Authors: Whitfield John B. , Zhu Gu , Landers J. George , Martin Nicholas G.
Published: July 2020

Scores on an optimistic-pessimistic personality scale have been associated with mortality, but optimism and pessimism scores are separable traits and it is unclear which has effects on health or longevity. The Life Orientation Test (LOT), containing items for optimism and pessimism, was included in a twin study on health of Australians aged over 50 in 1993–1995. After a mean of 20 years, participants were matched against death information from the Australian National Death Index. 1,068 out of 2,978 participants with useable LOT scores had died. Survival analysis tested for associations between separate optimism and pessimism scores and mortality from any cause, and from cancers, cardiovascular diseases or other known causes. Age-adjusted scores on the pessimism scale were associated with all-cause and cardiovascular mortality (Hazard Ratios per 1 standard deviation unit, 95% confidence intervals and p-values 1.134, 1.065–1.207, 8.85 × 10–5 and 1.196, 1.045–1.368, 0.0093, respectively) but not with cancer deaths. Optimism scores, which were only weakly correlated with pessimism scores (age-adjusted rank correlation = − 0.176), did not show significant associations with overall or cause-specific mortality. Reverse causation (disease causing pessimism) is unlikely because in that case both cardiovascular diseases and cancers would be expected to lead to pessimism.
Cover crops and chicken grazing in a winter fallow field improve soil carbon and nitrogen contents and decrease methane emissions
Authors: Zheng Huabin , Zhou Linhong , Wei Jiabing , Tang Qiyuan , Zou Yingbin , Tang Jianwu , Xu Huaqin
Published: July 2020

Using symbiotic farming methods [cover crops and chicken grazing (+ C)] in a winter fallow field, we found that the soil organic matter and total nitrogen of the + C treatment were 5.2% and 26.6% higher, respectively, than those of a treatment with cover crops and no chicken grazing (− C). The annual rice grain yield of the + C treatment was 3.8% higher than that of the − C treatment and 12.3% higher than that of the bare fallow field (CK), while the annual CH4 emissions of the + C treatment were 26.9% lower than those of the − C treatment and 10.6% lower than those of the CK treatment. The 100-year global warming potential of the + C treatment was 6.2% lower than that of the − C treatment. Therefore, the use of winter cover crops and chicken grazing in a winter fallow field was effective at reducing CH4 emissions and significantly improving soil nutrients and rice yield.
C22 podovirus infectivity is associated with intermediate stiffness
Authors: Sae-Ueng Udom , Bhunchoth Anjana , Phironrit Namthip , Treetong Alongkot , Sapcharoenkun Chaweewan , Chatchawankanphanich Orawan , Leartsakulpanich Ubolsree , Chitnumsub Penchit
Published: July 2020

Bacteriophages have potential for use as biological control agents (biocontrols) of pathogenic bacteria, but their low stability is limiting for their utilization as biocontrols. Understanding of the conditions conducive to storage of phages in which infectivity is maintained over long periods will be useful for their application as biocontrols. We employed a nanomechanical approach to study how external environmental factors affect surface properties and infectivity of the podovirus C22 phage, a candidate for biocontrol of Ralstonia solanacearum, the agent of bacterial wilt in crops. We performed atomic force microscopy (AFM)-based nano-indentation on the C22 phage in buffers with varying pH and ionic strength. The infectivity data from plaque assay in the same conditions revealed that an intermediate range of stiffness was associated with phage titer that remained consistently high, even after prolonged storage up to 182 days. The data are consistent with the model that C22 phage must adopt a metastable state for maximal infectivity, and external factors that alter the stiffness of the phage capsid lead to perturbation of this infective state.