bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperactivation of monocytes and macrophages in MCI patients contributes to the progression of Alzheimer's disease
Authors: Munawara Usma , Catanzaro Michael , Xu Weili , Tan Crystal , Hirokawa Katsuiku , Bosco Nabil , Dumoulin David , Khalil Abdelouahed , Larbi Anis , Lévesque Simon , Ramassamy Charles , Barron Annelise E. , Cunnane Stephen , Beauregard Pascale B. , Bellenger Jean-Pierre , Rodrigues Serafim , Desroches Mathieu , Witkowski Jacek M. , Laurent Benoit , Frost Eric H. , Fulop Tamas
Published: June 2021

Background

Alzheimer’s disease (AD) is the most common neurodegenerative disease ultimately manifesting as clinical dementia. Despite considerable effort and ample experimental data, the role of neuroinflammation related to systemic inflammation is still unsettled. While the implication of microglia is well recognized, the exact contribution of peripheral monocytes/macrophages is still largely unknown, especially concerning their role in the various stages of AD.

Objectives

AD develops over decades and its clinical manifestation is preceded by subjective memory complaints (SMC) and mild cognitive impairment (MCI); thus, the question arises how the peripheral innate immune response changes with the progression of the disease. Therefore, to further investigate the roles of monocytes/macrophages in the progression of AD we assessed their phenotypes and functions in patients at SMC, MCI and AD stages and compared them with cognitively healthy controls. We also conceptualised an idealised mathematical model to explain the functionality of monocytes/macrophages along the progression of the disease.

Results

We show that there are distinct phenotypic and functional changes in monocyte and macrophage populations as the disease progresses. Higher free radical production upon stimulation could already be observed for the monocytes of SMC patients. The most striking results show that activation of peripheral monocytes (hyperactivation) is the strongest in the MCI group, at the prodromal stage of the disease. Monocytes exhibit significantly increased chemotaxis, free radical production, and cytokine production in response to TLR2 and TLR4 stimulation.

Conclusion

Our data suggest that the peripheral innate immune system is activated during the progression from SMC through MCI to AD, with the highest levels of activation being in MCI subjects and the lowest in AD patients. Some of these parameters may be used as biomarkers, but more holistic immune studies are needed to find the best period of the disease for clinical intervention.
Hemophagocytic lymphohistiocytosis during pregnancy: a review of the literature in epidemiology, pathogenesis, diagnosis and treatment
Authors: Liu Lidong , Cui Yutong , Zhou Qiongjie , Zhao Huanqiang , Li Xiaotian
Published: June 2021

Hemophagocytic lymphohistiocytosis during pregnancy is rare; it is often misdiagnosed, resulting in a high maternal and foetal mortality rate. Herein, based on limited case reports including antepartum and postpartum cases, we reviewed the current studies of pregnancy-related hemophagocytic lymphohistiocytosis, and compared the epidemiology, aetiology, diagnosis and treatment of pregnancy-related hemophagocytic lymphohistiocytosis with non-pregnancy, enriching the understanding of hemophagocytic lymphohistiocytosis and its treatment in obstetrics.
Lung distribution of gas and blood volume in critically ill COVID-19 patients: a quantitative dual-energy computed tomography study
Authors: Ball Lorenzo , Robba Chiara , Herrmann Jacob , Gerard Sarah E. , Xin Yi , Mandelli Maura , Battaglini Denise , Brunetti Iole , Minetti Giuseppe , Seitun Sara , Bovio Giulio , Vena Antonio , Giacobbe Daniele Roberto , Bassetti Matteo , Rocco Patricia R. M. , Cereda Maurizio , Rizi Rahim R. , Castellan Lucio , Patroniti Nicolò , Pelosi Paolo ,   Collaborators of the GECOVID Group, Bixio Mattia , Gratarola Angelo , Frisoni Paolo , Loconte Maurizio , Molin Alexandre , Orefice Giulia , Ciaravolo Elena , Costantino Federico , Battioni Dario , Buconte Gerolama , Casaleggio Alessandro , Cittadini Giuseppe , Dogliotti Luca , Giasotto Veronica , Perissi Sara , Pigati Maria , Santacroce Elena , Zaottini Federico , Dentone Chiara , Taramasso Lucia , Magnasco Laura , Bastianello Matilde
Published: June 2021

Background

Critically ill COVID-19 patients have pathophysiological lung features characterized by perfusion abnormalities. However, to date no study has evaluated whether the changes in the distribution of pulmonary gas and blood volume are associated with the severity of gas-exchange impairment and the type of respiratory support (non-invasive versus invasive) in patients with severe COVID-19 pneumonia.

Methods

This was a single-center, retrospective cohort study conducted in a tertiary care hospital in Northern Italy during the first pandemic wave. Pulmonary gas and blood distribution was assessed using a technique for quantitative analysis of dual-energy computed tomography. Lung aeration loss (reflected by percentage of normally aerated lung tissue) and the extent of gas:blood volume mismatch (percentage of non-aerated, perfused lung tissue—shunt; aerated, non-perfused dead space; and non-aerated/non-perfused regions) were evaluated in critically ill COVID-19 patients with different clinical severity as reflected by the need for non-invasive or invasive respiratory support.

Results

Thirty-five patients admitted to the intensive care unit between February 29th and May 30th, 2020 were included. Patients requiring invasive versus non-invasive mechanical ventilation had both a lower percentage of normally aerated lung tissue (median [interquartile range] 33% [24–49%] vs. 63% [44–68%], p < 0.001); and a larger extent of gas:blood volume mismatch (43% [30–49%] vs. 25% [14–28%], p = 0.001), due to higher shunt (23% [15–32%] vs. 5% [2–16%], p = 0.001) and non-aerated/non perfused regions (5% [3–10%] vs. 1% [0–2%], p = 0.001). The PaO2/FiO2 ratio correlated positively with normally aerated tissue (ρ = 0.730, p < 0.001) and negatively with the extent of gas-blood volume mismatch (ρ = − 0.633, p < 0.001).

Conclusions

In critically ill patients with severe COVID-19 pneumonia, the need for invasive mechanical ventilation and oxygenation impairment were associated with loss of aeration and the extent of gas:blood volume mismatch.

Graphic abstract
SPARK-X: non-parametric modeling enables scalable and robust detection of spatial expression patterns for large spatial transcriptomic studies
Authors: Zhu Jiaqiang , Sun Shiquan , Zhou Xiang
Published: June 2021

Spatial transcriptomic studies are becoming increasingly common and large, posing important statistical and computational challenges for many analytic tasks. Here, we present SPARK-X, a non-parametric method for rapid and effective detection of spatially expressed genes in large spatial transcriptomic studies. SPARK-X not only produces effective type I error control and high power but also brings orders of magnitude computational savings. We apply SPARK-X to analyze three large datasets, one of which is only analyzable by SPARK-X. In these data, SPARK-X identifies many spatially expressed genes including those that are spatially expressed within the same cell type, revealing new biological insights.
Systems pharmacogenomics identifies novel targets and clinically actionable therapeutics for medulloblastoma
Authors: Genovesi Laura A. , Millar Amanda , Tolson Elissa , Singleton Matthew , Hassall Emily , Kojic Marija , Brighi Caterina , Girard Emily , Andradas Clara , Kuchibhotla Mani , Bhuva Dharmesh D. , Endersby Raelene , Gottardo Nicholas G. , Bernard Anne , Adolphe Christelle , Olson James M. , Taylor Michael D. , Davis Melissa J. , Wainwright Brandon J.
Published: June 2021

Background

Medulloblastoma (MB) is the most common malignant paediatric brain tumour and a leading cause of cancer-related mortality and morbidity. Existing treatment protocols are aggressive in nature resulting in significant neurological, intellectual and physical disabilities for the children undergoing treatment. Thus, there is an urgent need for improved, targeted therapies that minimize these harmful side effects.

Methods

We identified candidate drugs for MB using a network-based systems-pharmacogenomics approach: based on results from a functional genomics screen, we identified a network of interactions implicated in human MB growth regulation. We then integrated drugs and their known mechanisms of action, along with gene expression data from a large collection of medulloblastoma patients to identify drugs with potential to treat MB.

Results

Our analyses identified drugs targeting CDK4, CDK6 and AURKA as strong candidates for MB; all of these genes are well validated as drug targets in other tumour types. We also identified non-WNT MB as a novel indication for drugs targeting TUBB, CAD, SNRPA, SLC1A5, PTPRS, P4HB and CHEK2. Based upon these analyses, we subsequently demonstrated that one of these drugs, the new microtubule stabilizing agent, ixabepilone, blocked tumour growth in vivo in mice bearing patient-derived xenograft tumours of the Sonic Hedgehog and Group 3 subtype, providing the first demonstration of its efficacy in MB.

Conclusions

Our findings confirm that this data-driven systems pharmacogenomics strategy is a powerful approach for the discovery and validation of novel therapeutic candidates relevant to MB treatment, and along with data validating ixabepilone in PDX models of the two most aggressive subtypes of medulloblastoma, we present the network analysis framework as a resource for the field.
Biomechanical stress in the context of competitive sports training triggers enthesitis
Authors: Simon David , Kleyer Arnd , Bayat Sara , Knitza Johannes , Valor-Mendez Larissa , Schweiger Marina , Schett Georg , Tascilar Koray , Hueber Axel J.
Published: June 2021

Objective

To evaluate the influence of mechanical stress on the development of immediate enthesitis.

Methods

The BEAT study is an interventional study that assessed entheses in competitive badminton players before and immediately after a 60-min intensive training session. Power Doppler (PD) signal and Gray scale (GS) changes were assessed in the insertion sites of both Achilles tendon, patellar tendons, and lateral humeral epicondyles and quantified using a validated scoring system.

Results

Thirty-two badminton players were included. One hundred ninety-two entheseal sites were examined twice. The respective empirical total scores for PD examination were 0.1 (0.3) before and 0.5 (0.9) after training. Mean total GS scores were 2.9 (2.5) and 3.1 (2.5) before and after training, respectively. The mean total PD score difference of 0.4 between pre- and post-training was significant (p = 0.0014), whereas no significant difference for the mean total GS score was observed. Overall, seven participants (22%) showed an increased empirical total PD score. A mixed effects model showed a significant increase of PD scores after training, with a mean increase per site of 0.06 (95% CI 0.01 to 0.12, p = 0.017).

Conclusions

Mechanical stress leads to rapid inflammatory responses in the entheseal structures of humans. These data support the concept of mechanoinflammation in diseases associated with enthesitis.
A multi-OMIC characterisation of biodegradation and microbial community succession within the PET plastisphere
Authors: Wright Robyn J. , Bosch Rafael , Langille Morgan G. I. , Gibson Matthew I. , Christie-Oleza Joseph A.
Published: June 2021

Background

Plastics now pollute marine environments across the globe. On entering these environments, plastics are rapidly colonised by a diverse community of microorganisms termed the plastisphere. Members of the plastisphere have a myriad of diverse functions typically found in any biofilm but, additionally, a number of marine plastisphere studies have claimed the presence of plastic-biodegrading organisms, although with little mechanistic verification. Here, we obtained a microbial community from marine plastic debris and analysed the community succession across 6 weeks of incubation with different polyethylene terephthalate (PET) products as the sole carbon source, and further characterised the mechanisms involved in PET degradation by two bacterial isolates from the plastisphere.

Results

We found that all communities differed significantly from the inoculum and were dominated by Gammaproteobacteria, i.e. Alteromonadaceae and Thalassospiraceae at early time points, Alcanivoraceae at later time points and Vibrionaceae throughout. The large number of encoded enzymes involved in PET degradation found in predicted metagenomes and the observation of polymer oxidation by FTIR analyses both suggested PET degradation was occurring. However, we were unable to detect intermediates of PET hydrolysis with metabolomic analyses, which may be attributed to their rapid depletion by the complex community. To further confirm the PET biodegrading potential within the plastisphere of marine plastic debris, we used a combined proteogenomic and metabolomic approach to characterise amorphous PET degradation by two novel marine isolates, Thioclava sp. BHET1 and Bacillus sp. BHET2. The identification of PET hydrolytic intermediates by metabolomics confirmed that both isolates were able to degrade PET. High-throughput proteomics revealed that whilst Thioclava sp. BHET1 used the degradation pathway identified in terrestrial environment counterparts, these were absent in Bacillus sp. BHET2, indicating that either the enzymes used by this bacterium share little homology with those characterised previously, or that this bacterium uses a novel pathway for PET degradation.

Conclusions

Overall, the results of our multi-OMIC characterisation of PET degradation provide a significant step forwards in our understanding of marine plastic degradation by bacterial isolates and communities and evidences the biodegrading potential extant in the plastisphere of marine plastic debris.
Sociotechnical imaginaries of a secure future
Authors: Gerhold Lars , Brandes Edda
Published: June 2021

The article examines the increasingly important role played by technology in the domain of public security in Germany, illustrating its effects on social life. In order to illuminate developments that govern the adoption of security technologies and render them in their dependencies comprehensible, we present two plausible and consistent future scenarios for Germany 2035. Following Jasanoff and Kim, these scenarios are theoretically conceived as two competing “sociotechnical imaginaries” which implies different trajectories for shaping the future. In these imaginaries, security technologies condition social change, and vice versa, in a mutually interdependent process. On the basis of current literature in tandem with a structured scenario development process, we condensed the present sociotechnical imaginaries into two tangible future scenarios for the field of public security, illustrating its effects on how we live as a society. Our overarching goal is to identify key factors that will mediate future developments, and, by extension, to facilitate discussion on the type of future we find collectively desirable. The analysis of impact factors resulted in ten key factors that play a crucial role for the use of security technologies and serve as a leverage for shaping the future. Projections of these factors lead to two narrative scenarios “To Be Ahead” and “Turn Back The Clock”.
The effects of water temperature, acoustic tag type, size at tagging, and surgeon experience on juvenile Chinook salmon (Oncorhynchus tshawytscha) tag retention and growth
Authors: Robinson Rebecca R. , Notch Jeremy , McHuron Alex , Logston Renae , Pham Tom , Ammann Arnold J.
Published: June 2021

Background

Acoustic telemetry is a widely used tool to study the movement and survival of juvenile fish and often requires a surgical procedure to implant the transmitter, which may impact overall fitness and survival following release. This is an important consideration when implementing large-scale acoustic telemetry projects aimed at estimating outmigration survival. The objective of this study was to examine the effects of water temperature, tag type, size at tagging, and surgeon experience on tag retention and growth rate of juvenile Chinook salmon (Oncorhynchus tshawytscha). We tagged 128 spring-run Chinook salmon (81–97 mm fork length, 5.2–10.0 g, tag burden 2.4–6.0%) with one of two types of acoustic transmitters; a shorter, heavier model (‘standard’) and a longer, lighter model (‘injectable’). Fish were tagged by either a novice or experienced surgeon. An additional 64 untagged fish served as a control group and were split between temperature treatments. Fish were reared in either cool (mean 13.4 °C) or warm (mean 17.8 °C) water for 60 days, prior to being euthanized, weighed and measured.

Results

Tag retention was similar for both transmitter types, but varied with water temperature, with significantly higher tag loss in the warm treatment (21.9%, 14 tags expelled), compared to the cold treatment (7.8%, 5 tags expelled). In the warm treatment, fish growth in the injectable tag group was significantly lower compared to the control group, and lower than the standard tag group, but not significantly lower. There was no significant difference between the control and standard tag groups for the warm treatment. In the cool temperature treatment, fish growth was not significantly different among any of the factors tested. Surgery time differed between surgeons; however, surgeon experience did not significantly affect tag shedding or growth.

Conclusion

Total tag loss was 14.8% over the 60-day trial, with higher and earlier loss in the warmer treatment. Tag length may be a more important factor than tag weight in smaller size fish. This suggests that tag shedding is a significant factor to consider when estimating survival, as the actual survival rate may be higher than estimates based solely on receiver detections.
Prevalence and predictors of psychological distress following injury: findings from a prospective cohort study
Authors: Richardson Amy E. , Derrett Sarah , Samaranayaka Ariyapala , Wyeth Emma H.
Published: June 2021

Background

Research examining psychological distress in people who have experienced an injury has focused on those with serious injuries or specific injury types, and has not involved long-term follow up. The aims of this investigation were to describe the prevalence of, and factors contributing to, psychological distress in a cohort of people with a broad range of injuries.

Methods

The Prospective Outcomes of Injury Study (POIS) is a longitudinal cohort study of 2856 injured New Zealanders recruited from a national insurance entitlement claims register between 2007 and 2009. Participants were interviewed approximately 3, 12, and 24 months after their injury. The Kessler Psychological Distress Scale (K6) was used to measure psychological distress at each interview.

Results

25% of participants reported clinically relevant distress (K6 ≥ 8) 3 months post-injury, 15% reported distress at 12 months, and 16% reported distress at 24 months. Being 45 years or older, Māori or Pacific ethnicity, experiencing pre-injury mental health conditions, having inadequate pre-injury income, reporting poor pre-injury health or trouble accessing healthcare, having a severe injury or an injury resulting from assault, and reporting clinically relevant distress 3 months post-injury were independently associated with an increased risk of distress 12 months post-injury. The majority of these associations were also evident with respect to distress 24 months post-injury.

Conclusions

Distress is common after injury among people with a broad range of injury types and severities. Screening for distress early after injury is important to identify individuals in need of targeted support.
Mineralogical and physico-chemical properties of halloysite-bearing slip surface material from a landslide during the 2018 Eastern Iburi earthquake, Hokkaido
Authors: Kameda Jun
Published: June 2021

Destructive landslides were triggered by the 6.7 MwEastern Iburi earthquake that struck southern Hokkaido, Japan, on 6 September 2018. Heavy rainfall on 4 September in addition to intermittent rainfall around the Iburi Tobu area saturated and weakened the slope-forming materials (mostly altered volcanoclastic soils), making them susceptible to failure because of the earthquake’s strong ground motion. Most of the shallow landslides exhibited long runouts along gentle hill slopes, with characteristic halloysite-bearing slip surface at the base of the volcanic soils. This study investigated the mineralogical and physico-chemical properties of the slip surface material with the aim of understanding weakening and post-failure behaviors during the landslides. Halloysite in the slip surface had irregular-to-hollow-spherical morphology with higher mesopore volumes than tubular halloysite, which is related to a high capacity for water retention after rainfall. To reproduce possible chemical changes in the slip surface during rainfall, the sample was immersed in varying amounts of rainwater; solution pH increased and ionic strength decreased with increasing water content. These findings, alongside electrophoretic analysis, suggest that rainwater infiltration could have increased the absolute zeta potential value of the slip surface material. It is suggested that rainfall before the earthquake enhanced the colloidal stability of halloysite particles within the slip surface, owing to an increase in electrostatic repulsion. This decreased the material’s cohesive strength, which might have led to destabilization of the slope during ground shaking generated by the earthquake, and subsequent high-mobility flow after failure.
The digestive tract as an essential organ for water acquisition in marine teleosts: lessons from euryhaline eels
Authors: Takei Yoshio
Published: June 2021

Adaptation to a hypertonic marine environment is one of the major topics in animal physiology research. Marine teleosts lose water osmotically from the gills and compensate for this loss by drinking surrounding seawater and absorbing water from the intestine. This situation is in contrast to that in mammals, which experience a net osmotic loss of water after drinking seawater. Water absorption in fishes is made possible by (1) removal of monovalent ions (desalinization) by the esophagus, (2) removal of divalent ions as carbonate (Mg/CaCO3) precipitates promoted by HCO3− secretion, and (3) facilitation of NaCl and water absorption from diluted seawater by the intestine using a suite of unique transporters. As a result, 70–85% of ingested seawater is absorbed during its passage through the digestive tract. Thus, the digestive tract is an essential organ for marine teleost survival in the hypertonic seawater environment. The eel is a species that has been frequently used for osmoregulation research in laboratories worldwide. The eel possesses many advantages as an experimental animal for osmoregulation studies, one of which is its outstanding euryhalinity, which enables researchers to examine changes in the structure and function of the digestive tract after direct transfer from freshwater to seawater. In recent years, the molecular mechanisms of ion and water transport across epithelial cells (the transcellular route) and through tight junctions (the paracellular route) have been elucidated for the esophagus and intestine. Thanks to the rapid progress in analytical methods for genome databases on teleosts, including the eel, the molecular identities of transporters, channels, pumps and junctional proteins have been clarified at the isoform level. As 10 y have passed since the previous reviews on this subject, it seems relevant and timely to summarize recent progress in research on the molecular mechanisms of water and ion transport in the digestive tract in eels and to compare the mechanisms with those of other teleosts and mammals from comparative and evolutionary viewpoints. We also propose future directions for this research field to achieve integrative understanding of the role of the digestive tract in adaptation to seawater with regard to pathways/mechanisms including the paracellular route, divalent ion absorption, metabolon formation and cellular trafficking of transporters. Notably, some of these have already attracted practical attention in laboratories.
Bridging the state and market logics of refugee labour market inclusion – a comparative study on the inclusion activities of German professional chambers
Authors: Maletzky de García Martina
Published: June 2021

Due to their high numbers, refugees’ labour market inclusion has become an important topic for Germany in recent years. Because of a lack of research on meso-level actors’ influences on labour market inclusion and the transcendent role of organizations in modern societies, the article focuses on the German professional chambers’ role in the process of refugee inclusion. The study shows that professional chambers are intermediaries between economic actors, the government and refugees, which all follow their own logics and ideas of labour market inclusion (the state, the market and the community logic). The measures taken by professional chambers mainly reflect a governmental logic (to reduce refugee unemployment) combined with a market logic (to provide human resources to economic actors). A community logic (altruism) only comes into play as a rather unintended consequence of measures addressing the other two logics. The measures of two types of professional chambers are compared. Close similarities between them reveal that the organization type is of theoretical relevance to explain the type of measures organizations opt for.
Sero-molecular epidemiology of hepatitis E virus in pigs and human contacts in Ghana
Authors: Yeboah Richmond , Sylverken Augustina Angelina , Owusu Michael , El-Duah Philip , Burimuah Vitus , Frimpong Yaw , Lamptey Jones , Eckerle Isabella , Meyer Benjamin , Antwi Christopher , Agbenyaga Olivia , Folitse Raphael , Emikpe Benjamin , Oppong Samuel Kingsley , Adu-Sarkodie Yaw , Drosten Christian
Published: June 2021

Background

Hepatitis E virus (HEV) is among the leading causes of viral hepatitis in most developing countries. Zoonotic acquisition of HEV genotype 3 from swine has come into focus more recently. Available studies on HEV in Ghana and other countries in the region do not provide enough information towards understanding the epidemiology of HEV in human and animal populations. Towards this end, we conducted a comparative cross-sectional study to determine the seroprevalence and risk factors associated with HEV exposure, both in swine and humans working on pig farms in typical local settings. The presence of viral RNA in human and swine samples was also evaluated, along with classification of viral sequences from HEV-positive samples.

Methods

Structured questionnaires soliciting information on pigs reared, as well as socio-demographic information including age, sex and educational background of humans was collected. A total of 10 ml and 5 ml of whole blood was collected from pigs and human participants respectively. ELISA and real-time RT-PCR were performed on the sera for the qualitative detection of IgG antibodies to hepatitis E virus and viral RNA, respectively.

Results

Five hundred and forty-four (544) human participants including 264 swine contacts and 280 swine non-contacts were enrolled in the study. Although the proportion of HEV IgG antibodies was higher in contact groups (114; 54.3%) than non-contact groups (96; 45.7%), a multivariate analysis did not show any significant difference. No HEV RNA was detected in human samples. Similarly, 720 pigs were sampled from 18 farms located in five regions in Ghana. Twenty-three (23) of the pigs (3.2, 95%CI = 2.0–4.8) were positive for HEV RNA by real-time RT-PCR testing. Sequences obtained from HEV-positive samples were found to share high sequence identities with each other and clustered with other genotype 3 viruses indicating the existence of circulating zoonotic genotype 3 viruses on farms. Although we did not find evidence of pig to human transmission of HEV genotype 3, the presence of this genotype in pigs shows the potential for possible zoonotic transmission in African farm settings and buttresses the importance of active surveillance for the infection among at risk populations.
A simplified method for calculating spectral emission of nonequilibrium air plasmas in hypersonic shock-layers
Authors: He Xin , Gao Cheng , Jiang Tao
Published: June 2021

A simplified method for calculating the spectral emission of nonequilibrium air plasmas is developed. In order to obtain the nonequilibrium energy level populations, the nonequilibrium coefficients are introduced into the Saha-Boltzmann equation. These nonequilibrium coefficients are calculated by using several significant radiative processes. An approach to the determination of nonequilibrium electronic energy level populations of diatomic molecules is also presented. Based on the method, spectral emission of atoms and molecules in a typical air plasma cell is investigated. The results reveal that there is a significant difference between the nonequilibrium and equilibrium emission. We apply the method to the nonequilibrium AVCO R-156 experiment. Good agreement with the NEQAIR code and the measured data is shown, indicating that the method is reasonable and has good accuracy.
Sustaining implementation facilitation: a model for facilitator resilience
Authors: Olmos-Ochoa Tanya T. , Ganz David A. , Barnard Jenny M. , Penney Lauren , Finley Erin P. , Hamilton Alison B. , Chawla Neetu
Published: June 2021

Background

Implementation facilitators enable healthcare staff to effectively implement change, yet little is known about their affective (e.g., emotional, mental, physical) experiences of facilitation. We propose an expansion to the Integrated Promoting Action on Research in Health Services (i-PARIHS) framework that introduces facilitation intensity and facilitator resilience to better assess facilitators’ affective experiences.

Methods

We used an instrumental case study and facilitator data (logged reflections and debrief session notes) from the Coordination Toolkit and Coaching initiative to conceptualize facilitation intensity and facilitator resilience and to better understand the psychological impact of the facilitation process on facilitator effectiveness and implementation success.

Results

We define facilitation intensity as both the quantitative and/or qualitative measure of the volume of tasks and activities needed to engage and motivate recipients in implementation, and the psychological impact on the facilitator of conducting facilitation tasks and activities. We define facilitator resilience as the ability to cope with and adapt to the complexities of facilitation in order to effectively engage and motivate staff, while nurturing and sustaining hope, self-efficacy, and adaptive coping behaviors in oneself.

Conclusions

Facilitators’ affective experience may help to identify potential relationships between the facilitation factors we propose (facilitation intensity and facilitator resilience). Future studies should test ways of reliably measuring facilitation intensity and facilitator resilience and specify their relationships in greater detail. By supporting facilitator resilience, healthcare delivery systems may help sustain the skilled facilitator workforce necessary for continued practice improvement.

Trial registration

The project was registered with ClinicalTrials.gov (NCT03063294) on February 24, 2017.
An algorithm to simulate nonstationary and non-Gaussian stochastic processes
Authors: Hong H. P. , Cui X. Z. , Qiao D.
Published: June 2021

We proposed a new iterative power and amplitude correction (IPAC) algorithm to simulate nonstationary and non-Gaussian processes. The proposed algorithm is rooted in the concept of defining the stochastic processes in the transform domain, which is elaborated and extend. The algorithm extends the iterative amplitude adjusted Fourier transform algorithm for generating surrogate and the spectral correction algorithm for simulating stationary non-Gaussian process. The IPAC algorithm can be used with different popular transforms, such as the Fourier transform, S-transform, and continuous wavelet transforms. The targets for the simulation are the marginal probability distribution function of the process and the power spectral density function of the process that is defined based on the variables in the transform domain for the adopted transform. The algorithm is versatile and efficient. Its application is illustrated using several numerical examples.
Effects of the ABCB1 c.3435C>T (rs1045642) Polymorphism on Heat Pain Perception in Opioid-Free Adults With Chronic Pain
Authors: Hooten W. Michael , Hu Danqing , Cunningham Julie M.
Published: June 2021

BACKGROUND:

The adenosine triphosphate-binding cassette, subfamily B, member 1 gene (ABCB1) encodes P-glycoprotein (P-gp) that influences the intracellular transport of solutes including endogenous opioid peptides. The primary objective of this study was to determine the effects of the ABCB1 polymorphism c.3435C>T (rs10454642) on heat pain (HP) perception in a group of opioid-free adults with chronic pain.

METHODS:

Opioid-free adults with chronic pain consecutively admitted to a pain rehabilitation program comprised the study cohort (N = 134). Individuals were genotyped for the c.3435C>T (rs10454642) polymorphism. The polymorphism was analyzed with nonparametric tests using a dominant (cytosine-cytosine [CC] versus cytosine-thymine [CT] + thymine-thymine [TT]) and recessive (CC + CT versus TT) model of allele effects. Quantitative sensory testing was performed using the Computer Aided Sensory Evaluator IV system.

RESULTS:

The distribution of genotypes was 22% (N = 29) for CC, 45% (N = 60) for CT, and 33% (N = 45) for TT (Hardy-Weinberg, P > .1). A significant association was observed between the recessive model and HP threshold. Standardized values of HP threshold were significantly greater in the TT group than the CC + CT group (median difference, −0.77; 95% confidence interval [CI], −1.49 to −0.23; P = .005), and the effect size estimate was small (Cliff delta = 0.30). In the dominant model, no significant difference in HP threshold was observed between the CC and CT + TT groups (median difference, −0.45; 95% CI, −1.15 to 0.00; P = .108).

CONCLUSIONS:

These results posit that the efflux of endogenous opioid peptides is reduced in individuals with the TT genotype due to lower expression of P-gp, which, in turn, results in higher HP threshold. This study contributes to the emerging understanding of how the ABCB1 c.3435C>T polymorphism contributes to pain perception in opioid-free adults with chronic pain and provides the foundation for investigating the potential effects of this polymorphism on the clinical course of chronic pain.
Textual Authority in the Vita Nova’s Nineteenth-Century Editions
Authors: Todorović Jelena
Published: June 2021

This article focuses on the nineteenth-century print circulation of Dante’s Vita Nova (1292–94) and especially on the response in print media to the tension between new critical approaches to text editing, on the one hand, and editors’ dependence on the text’s complex history on the other. At the center of this discussion is one of the thorniest aspects of the Vita Nova’s text: the divisions (technical prose of a scholastic nature in which Dante explains the formal structure of his poems). Over the centuries, Dante’s authority over his own text was brought into question on account of the inclusion in the literary text of what readers and editors considered to be commentary. Even though in the second half of the nineteenth century the editors began recognizing the divisions’ rightful place within the libello’s text, they continued—operating within the centuries-long tradition that did not consider them “text” but rather “gloss”—to engage in efforts to differentiate them from the rest of the text in order to point out their different textual nature.
FOXO1 mediates hypoxia-induced G0/G1 arrest in ovarian somatic granulosa cells by activating the TP53INP1-p53-CDKN1A pathway
Authors: Li Chengyu , Liu Zhaojun , Wu Gang , Zang Ziyu , Zhang Jia-Qing , Li Xiaoxuan , Tao Jingli , Shen Ming , Liu Honglin
Published: June 2021

The development of ovarian follicles constitutes the foundation of female reproduction. The proliferation of granulosa cells (GCs) is a basic process required to ensure normal follicular development. However, the mechanisms involved in controlling GC cell cycle are not fully understood. Here, by performing gene expression profiling in the domestic pig (Sus scrofa), we showed that cell cycle arrest at G0/G1 phase is highly correlated with pathways associated with hypoxic stress and FOXO signalling. Specifically, the elevated proportion of GCs at the arrested G0/G1 phase was accompanied by increased nuclear translocation of FOXO1 under conditions of hypoxia both in vivo and in vitro. Furthermore, phosphorylation of 14-3-3 by the JNK kinase is required for hypoxia-mediated FOXO1 activation and the resultant G0/G1 arrest. Notably, a FOXO1 mutant without DNA-binding activity failed to induce G0/G1 arrest of GCs during hypoxia. Importantly, we identified a new target gene of FOXO1, namely TP53INP1, which contributes to suppression of the G1-S cell cycle transition in response to hypoxia. Furthermore, we demonstrated that the inhibitory effect of the FOXO1-TP53INP1 axis on the GC cell cycle is mediated through a p53-CDKN1A-dependent mechanism. These findings could provide avenues for the clinical treatment of human infertility caused by impaired follicular development.
Structural variability and dynamics in the ectodomain of an ancestral-type classical cadherin revealed by AFM imaging
Authors: Nishiguchi Shigetaka , Oda Hiroki
Published: June 2021

Type III cadherin represents the ancestral form of classical cadherin in bilaterian metazoans. Drosophila possesses type III and type IVa cadherins, known as DN- and DE-cadherins, respectively. Mature DN- and DE-cadherins have 15 and 7 extracellular cadherin domain (EC) repeats, respectively, with DN-cadherin EC6–EC11 homologous to DE-cadherin EC1–EC6. These EC repeats contain predicted complete or partial Ca2+-free inter-EC linkers that potentially contribute to adhesion. Comparative structure–function studies of DN- and DE-cadherins may help us understand the ancestral and derived states of classical cadherin-mediated adhesion mechanisms. Here, using bead aggregation assays, we found that DN-cadherin EC1–EC11 and DE-cadherin EC1–EC6 exhibit Ca2+-dependent adhesive properties. Using high-speed atomic force microscopy (HS-AFM) imaging in solution, we show that both DN- and DE-cadherin ectodomains share a common morphological framework consisting of a strand-like and a globule-like portion. Furthermore, the DN-cadherin EC repeats are highly variable, flexible in morphology and have at least three bendable sites, one of which is located in EC6–EC11 and can act as a flexible hinge. Our findings provide insights into diversification of classical cadherin-mediated adhesion mechanisms.

This article has an associated First Person interview with the first author of the paper.
Generation of propulsive force via vertical undulations in snakes
Authors: Jurestovsky Derek J. , Usher Logan R. , Astley Henry C.
Published: June 2021

Lateral undulation is the most widespread mode of terrestrial vertebrate limbless locomotion, in which posteriorly propagating horizontal waves press against environmental asperities (e.g. grass, rocks) and generate propulsive reaction forces. We hypothesized that snakes can generate propulsion using a similar mechanism of posteriorly propagating vertical waves pressing against suitably oriented environmental asperities. Using an array of horizontally oriented cylinders, one of which was equipped with force sensors, and a motion capture system, we found snakes generated substantial propulsive force and propulsive impulse with minimal contribution from lateral undulation. Additional tests showed that snakes could propel themselves via vertical undulations from a single suitable contact point, and this mechanism was replicated in a robotic model. Vertical undulations can provide snakes with a valuable locomotor tool for taking advantage of vertical asperities in a variety of habitats, potentially in combination with lateral undulation, to fully exploit the 3D structure of the habitat.
Early suppression of the endocannabinoid degrading enzymes FAAH and MAGL alters locomotor development in zebrafish
Authors: Sufian M. Shah , Amin M. Ruhul , Ali Declan W.
Published: June 2021

The fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) enzymes are the predominant catabolic regulators of the major endocannabinoids (eCBs) anadamide (AEA) and 2-arachidonoylglycerol (2-AG), respectively. The expression and roles of eCBs during early embryogenesis remain to be fully investigated. Here, we inhibited FAAH and MAGL in zebrafish embryos during the first 24 h of life and examined motor neuron and locomotor development at 2 and 5 days post fertilization (dpf). Application of the dual FAAH/MAGL inhibitor, JZL195 (2 µmol l−1), resulted in a reduction in primary and secondary motor neuron axonal branching. JZL195 also reduced nicotinic acetylcholine receptor (nAChR) expression at neuromuscular junctions. Application of URB597 (5 µmol l−1), a specific inhibitor of the FAAH enzyme, also decreased primary motor neuron branching but did not affect secondary motor neuron branching and nAChR expression. Interestingly, JZL184 (5 µmol l−1), a specific inhibitor of MAGL, showed no effects on motor neuron branching or nAChR expression. Co-treatment of the enzyme inhibitors with the CB1R inhibitor AM251 confirmed the involvement of CB1R in motor neuron branching. Disruption of FAAH or MAGL reduced larval swimming activity, and AM251 attenuated the JZL195- and URB597-induced locomotor changes, but not the effects of JZL184. Together, these findings indicate that inhibition of FAAH, or augmentation of AEA acting through CB1R during early development, may be responsible for locomotor deficiencies.
Ibn Kammūna’s Understanding of the Body
Authors: Pattabanoğlu Fatma Zehra
Published: June 2021

Ibn Kammūna (d. 1284) is one of the prominent names to have presented the new structuring that emerged after the classical period studies of Islamic philosophy following the 12th century. This article deals with his theory of the body, previously undiscussed in the academic community. The subject has been handled in connection with the philosophy of nature and metaphysics concerning questions such as how the body exists as a possible essence and how the principles guiding this process are reflected in the field of nature, as well as what the body is and what its constituent elements, types, qualities, and additions are. Thus, Ibn Kammūna has been determined to consider the first body to be the first sphere, the later bodies to occur in the process of emanation, and the cause of the body to be the intellect. In addition, he established the body consisting of matter and form to be continuous, to point to itself, and to be an infinitely divisible substance. However, he is observed to have not evaluated matter and form, which are constituent elements of the body, under the category of substance. Moreover, this article also reviews Ibn Kammūna’s approach to the main claims of the Peripatetic and Illuminationist traditions about the body contained in his original works and commentaries. Through the proofs and reasoning made in the details of these claims, Ibn Kammūna is understood to have thought mostly in line with Ibn Sīnā about the definition and essence of the body. He occasionally agreed with Suhrawardī about the properties and additions of the body. This study investigates how Ibn Kammūna shaped Ibn Sīnā’s theory of the body, upon which Suhrawardī had expanded, and whether its content is original in this context. Thus, I aim to contribute to the field by following the processes of change, expansion, and transfer of philosophical accumulation in Islamic thought after these two philosophers who had founded of the Peripatetic and Illuminationist schools.
Modern Astronomy in Ottoman Madrasa Circles in the First Half of the 19th Century
Authors: Güneş Orhan
Published: June 2021

The use of telescopes for scientific purposes has significantly changed our knowledge of the structure of the Solar System. By the mid-19th century, two new planets, a dozen asteroids, and dozens of satellites had been added to the five planets known since ancient times. The Ottoman scientific circles did not turn their back on these developments in the West but reflected them in their works. However, the main thesis about the transfer of current knowledge is that this transfer had mainly been done by modern educational institutions at a speed not too high. This claim is expressed more powerfully when considering the madrasa environment in particular. The literature states that the first work from a madrasa to mention the two new planets of Uranus and Neptune that were discovered in the modern period is Ḳonevī’s (d. circa 19th century) Tanqīḥ al-ashkāl, written after 1857. This means a delay of 76 years for Uranus and at least 11 years for Neptune. This article aims to demonstrate that the first works to mention Uranus and Neptune did not originate from modern educational institutions and that the delay regarding the transfer of information did not occur as mentioned in the literature. This study shows that the first work to mentions Uranus was Tashīl al-idrāk, written by Ḳuyucakḳlızāde (d. 1263/1847) in 1831 and originating from a madrasa and that the first work to mention Neptune was Ḥayātīzāde’s (d. 1267/1851) Afkār al-jabarūt, written in 1847, again originating from a madrasa, and published in 1848. Thus, this study hopes the exiting hypothesis in the literature, which has a great deal of support, will start to be questioned based on these examples.
The Hand Extending Beyond the Cosmos: Discussions on the Khalā’ [Void] Between the Baṣran and Baghdād Schools of Mu’tazila
Authors: Kandemir Ahmet Mekin
Published: June 2021

We can find the origins of the notion of void in the Kalām tradition’s recognition of atomism. However, the main debates on the subject appeared after the Greek philosophical heritage transitioned to the Islamic world in the 3 rd century of Hijra. The literature of Kalām, just as in the metaphysical tradition, has two main types for this void being discussed. The first one is the external void (extracosmic) in which the cosmos floats. In the sources of Kalām, the question of whether such a type of void exists is debated around the questions of whether anyone who might look beyond the cosmos can see anything or whether someone who stretches their hand outside the cosmos can move it. The second type of void, which occupies more of the mutakallimūn (Muslim theologians) agenda, is the internal void (intercosmic), assumed to be within the cosmos and between the body-forming atoms. This kind of void is discussed around the question of “Whether separating the two atoms is possible so that a third one can be inserted between them?” An ongoing discussion on the intercosmic void is found between the Baṣran and Baghdād Schools of Mu’tazila. Ibn Mattawayh and al-Nīsābūrī narrated the evidence presented in these discussions in their original form. The current essay discusses the debates between the two Schools and assesses the theoretical and experimental arguments both Schools present to justify their viewpoints, considering their philosophical origins.