bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Age and Knee Osteoarthritis on the Modular Control of Walking: A Pilot Study
Authors: Roelker Sarah A. , Koehn Rebekah R. , Caruthers Elena J. , Schmitt Laura C. , Chaudhari Ajit M.W. , Siston Robert A.
Published: May 2020

Older adults and individuals with knee osteoarthritis (KOA) often exhibit reduced locomotor function and altered muscle activity. Identifying age- and KOA-related changes to the modular control of gait may provide insight into the neurological mechanisms underlying reduced walking performance in these populations. The purpose of this pilot study was to determine if the modular control of walking differs between younger and older adults without KOA and adults with end-stage KOA. Kinematic, kinetic, and electromyography data were collected from ten younger (23.5 ± 3.1 years) and ten older (63.5 ± 3.4 years) adults without KOA and ten adults with KOA (64.0 ± 4.0 years) walking at their self-selected speed. Separate non-negative matrix factorizations of 500 bootstrapped samples determined the number of modules required to reconstruct each participant’s electromyography. The number of modules required in the younger adults (3.2 ± 0.4) was greater than in the individuals with KOA (2.3 ± 0.7;p= 0.002), though neither cohorts’ required number of modules differed significantly from the unimpaired older adults (2.7 ± 0.5;p≥ 0.113). A significant association between module number and walking speed was observed (r= 0.532;p= 0.003) and individuals with KOA walked significantly slower (0.095 ± 0.21 m/s) than younger adults (1.24 ± 0.15 m/s;p= 0.005). Individuals with KOA also exhibited altered module activation patterns and composition (which muscles are associated with each module) compared to unimpaired adults. These findings suggest aging alone may not significantly alter modular control; however, the combined effects of knee osteoarthritis and aging may together impair the modular control of gait.
Predictors of misconceptions, knowledge, attitudes, and practices of COVID-19 pandemic among a sample of Saudi population and its impact: a cross-sectional study
Authors: Baig Mukhtiar , Jameel Tahir , Alzahrani Sami H , Mirza Ahmad A , Gazzaz Zohair J , Ahmad Tauseef , Baig Fizzah , Almurashi Saleh H
Published: May 2020

Objectives

To explore the predictors of misconceptions, knowledge, attitudes, and practices of the COVID-19 pandemic among a sample of the Saudi population and its impact.

Design

An online cross-sectional study.

Setting

Jeddah, Saudi Arabia.

Participants

A total of 2006 participants [953(47.5%) females, and 1053(52.5%) males], and more than 18 years of age were included in the study.

Data collection and analysis

This cross-sectional survey was conducted at the Faculty of Medicine, Rabigh, King Abdulaziz University (KAU). The participants were approached by social media (SM). An online questionnaire was administered, and the data were analyzed on SPSS-26.

Results

The SM was the leading source of information 889(43.9%). Two-thirds of the participants, 1250(66.9%) had various misconceptions, and about one-third of the study participants 637(31.7%) had disturbed social, mental, and psychological wellbeing, and many participants became more religious. Two-thirds of the study participants, 1292(68.1%) had good knowledge score. The attitude was highly positive in 1867(93.1%) participants’, and the practice score was adequate in 1939(97.7%). The participants’ educational status was the predictor of good knowledge. Male gender and divorced ones were the predictor of poor practice scores and age 51-60 years, private jobholders, and students were the predictors of the good practice scores. The Saudi nationality was the predictor of participants’ positive attitude, while the male gender and divorced ones were predictors of a negative attitude. The male gender and higher education status were the predictors of good concepts, while the older age and job (own business) were the predictors of misconceptions.

Conclusion

Our study observed several predictors of misconceptions, knowledge, attitudes, and practices among the Saudi population. Our participants had a good realization of the impact of this pandemic.

Strengths and limitations

Ours is the first study involving the general population of Saudi Arabia at a time when COVID-19 has tremendously affected the society.

The use of a validated questionnaire has strengthened the study results.

The sample size is adequate and representing different segments of society.

One of the limitations is the convenience sampling method.

Besides, the study used an online questionnaire, so we could not reach the section of society that is not using the internet.
Winner-Takes-All Resource Competition Redirects Cascading Cell Fate Transitions
Authors: Zhang Rong , Goetz Hanah , Melendez-Alvarez Juan , Li Jiao , Ding Tian , Wang Xiao , Tian Xiao-Jun
Published: May 2020

Failure of modularity remains a significant challenge for synthetic gene circuits assembled with tested modules as they often do not function as expected. Competition over shared limited gene expression resources is a crucial underlying reason. Here, we first built a synthetic cascading bistable switches (Syn-CBS) circuit in a single strain with two coupled self-activation modules to achieve two successive cell fate transitions. Interestingly, we found that thein vivotransition path was redirected as the activation of one switch always prevailed against the other instead of the theoretically expected coactivation. This qualitatively different type of resource competition between the two modules follows a ‘winner-takes-all’ rule, where the winner is determined by the relative connection strength between the modules. To decouple the resource competition, we constructed a two-strain circuit, which achieved successive activation and stable coactivation of the two switches. We unveiled a nonlinear resource competition within synthetic gene circuits and provided a division of labor strategy to minimize unfavorable effects.
COVIDep platform for real-time reporting of vaccine target recommendations for SARS-CoV-2: Description and connections with COVID-19 immune responses and preclinical vaccine trials
Authors: Ahmed Syed Faraz , Quadeer Ahmed A. , McKay Matthew R.
Published: May 2020

We introduce COVIDep (https://COVIDep.ust.hk), a web-based platform that provides immune target recommendations for guiding SARS-CoV-2 vaccine development. COVIDep implements a protocol that pools together publicly-available genetic data for SARS-CoV-2 and epitope data for SARS-CoV to identify B cell and T cell epitopes that present potential immune targets for SARS-CoV-2. Correspondences between outputs of COVIDep and immune responses recorded in COVID-19 patients and preclinical vaccine trials are also indicated. The platform is user-friendly, flexible, and based on up-to-date data. It may help guide vaccine designs and associated experimental studies for SARS-CoV-2.
Activation of amino acid metabolic program in response to impaired glycolysis in cardiac HIF1 deficient mice
Authors: Menendez-Montes Ivan , Escobar Beatriz , Gomez Manuel J. , Albendea-Gomez Teresa , Palacios Beatriz , Bonzon Elena , Alonso Ana Vanessa , Ferrarini Alessia , Jimenez-Borreguero Luis Jesus , Vázquez Jesus , Martin-Puig Silvia
Published: May 2020

Hypoxia is an important environmental cue in heart development. Despite of extensive characterization of gain and loss of function models, there is disagreement about the impact of HIF1α elimination in cardiac tissue. Here, we used a new conditional knock out ofHif1ain NKX2.5 cardiac progenitors to assess the morphological and functional consequences of HIF1α loss in the developing heart. By combining histology, electron microscopy and high-throughout genomics, proteomics and metabolomics, we found that deletion of Hif1a leads to impaired embryonic glycolysis without influencing cardiomyocyte proliferation and results in an increased mitochondrial number, activation of a transient amino acid response and upregulation of HIF2α and ATF4 by E12.5.Hif1amutants display normal fatty acid oxidation metabolic profile and do not show any sign of cardiac dysfunction in the adulthood. Our results demonstrate that HIF1 signaling is dispensable for heart development and reveal the metabolic flexibility of the embryonic myocardium, opening the potential application of alternative energy sources as therapeutic interventions during ischemic events.
The TFIID subunit Taf4 is required for pancreatic beta cell function and identity
Authors: Kleiber Thomas , Davidson Guillaume , Mengus Gabrielle , Martianov Igor , Davidson Irwin
Published: May 2020

We selectively inactivated the Taf4 subunit of general transcription factor TFIID in adult murine pancreatic beta cells (BCs). Taf4 inactivation rapidly diminishes expression of critical genes involved in BC function leading to increased glycaemia, lowered plasma insulin levels, defective glucose-stimulated insulin secretion and in the longer term reduced BC mass through apoptosis of a subpopulation of BCs. Nevertheless, glycaemia and blood insulin levels are stabilised after 11 weeks with mutant animals showing long term survival. Bulk RNA-seq and ATAC-seq together with single cell RNA-seq on isolated Langerhans islets show that Taf4 loss leads to a remodelling of chromatin accessibility and gene expression not only in targeted BCs, but also alpha and delta cells. One week after Taf4-loss, cells with mixed BC, alpha and/or delta cell identities were observed as well as a BC population trans-differentiating into alpha-like cells. Computational analysis defines how known critical BC and alpha cell determinants may act in combination with additional transcription factors and the NuRF chromatin remodelling complex to promote BC trans-differentiation.
Common genetic variation influencing human white matter microstructure
Authors: Zhao Bingxin , Li Tengfei , Yang Yue , Wang Xifeng , Luo Tianyou , Shan Yue , Zhu Ziliang , Xiong Di , Hauberg Mads E. , Bendl Jaroslav , Fullard John F. , Roussos Panagiotis , Li Yun , Stein Jason L. , Zhu Hongtu
Published: May 2020

Brain regions communicate with each other via tracts of myelinated axons, commonly referred to as white matter. White matter microstructure can be measured in the living human brain using diffusion based magnetic resonance imaging (dMRI), and has been found to be altered in patients with neuropsychiatric disorders. Although under strong genetic control, few genetic variants influencing white matter microstructure have ever been identified. Here we identified common genetic variants influencing white matter microstructure using dMRI in 42,919 individuals (35,741 in the UK Biobank). The dMRIs were summarized into 215 white matter microstructure traits, including 105 measures from tract-specific functional principal component analysis. Genome-wide association analysis identified many novel white matter microstructure associated loci (P< 2.3 × 10−10). We identified shared genetic influences through genetic correlations between white matter tracts and 62 other complex traits, including stroke, neuropsychiatric disorders (e.g., ADHD, bipolar disorder, major depressive disorder, schizophrenia), cognition, neuroticism, chronotype, as well as non-brain traits. Common variants associated with white matter microstructure alter the function of regulatory elements in glial cells, particularly oligodendrocytes. White matter associated genes were enriched in pathways involved in brain disease pathogenesis, neurodevelopment process, and repair of white matter damage (P< 1.5 × 10−8). In summary, this large-scale tract-specific study provides a big step forward in understanding the genetic architecture of white matter and its genetic links to a wide spectrum of clinical outcomes.
A viral genome packaging motor transitions between cyclic and helical symmetry to translocate dsDNA
Authors: Woodson Michael , Pajak Joshua , Zhao Wei , Zhang Wei , Arya Gaurav , White Mark A. , Jardine Paul. J. , Morais Marc C.
Published: May 2020

Molecular segregation and biopolymer manipulation require the action of molecular motors to do work by applying directional forces to macromolecules. The additional strand conserved E (ASCE) ring motors are an ancient family of molecular motors responsible for diverse tasks ranging from biological polymer manipulation (e.g. protein degradation and chromosome segregation) to establishing and maintaining proton gradients across mitochondrial membranes. Viruses also utilize ASCE segregation motors to package their genomes into their protein capsids and serve as accessible experimental systems due to their relative simplicity. We show by CryoEM focused image reconstruction that ASCE ATPases in viral dsDNA packaging motors adopt helical symmetry complementary to their dsDNA substrates. Together with previous data, including structural results showing these ATPases in planar ring conformations, our results suggest that these motors cycle between helical and planar cyclical symmetry, providing a possible mechanism for directional translocation of DNA. We further note that similar changes in quaternary structure have been observed for proteasome and helicase motors, suggesting an ancient and common mechanism of force generation that has been adapted for specific tasks over the course of evolution.
Proofreading through spatial gradients
Authors: Galstyan Vahe , Husain Kabir , Xiao Fangzhou , Murugan Arvind , Phillips Rob
Published: May 2020

Key enzymatic processes in biology use the nonequilibrium error correction mechanism called kinetic proofreading to enhance their specificity. Kinetic proofreading typically requires several dedicated structural features in the enzyme, such as a nucleotide hydrolysis site and multiple enzyme–substrate conformations that delay product formation. Such requirements limit the applicability and the adaptability of traditional proofreading schemes. Here, we explore an alternative conceptual mechanism of error correction that achieves delays between substrate binding and subsequent product formation by having these events occur at distinct physical locations. The time taken by the enzyme–substrate complex to diffuse from one location to another is leveraged to discard wrong substrates. This mechanism does not require dedicated structural elements on the enzyme, making it easier to overlook in experiments but also making proofreading tunable on the fly. We discuss how tuning the length scales of enzyme or substrate concentration gradients changes the fidelity, speed and energy dissipation, and quantify the performance limitations imposed by realistic diffusion and reaction rates in the cell. Our work broadens the applicability of kinetic proofreading and sets the stage for the study of spatial gradients as a possible route to specificity.
Alternating dynamics oforiC, SMC and MksBEF in segregation ofPseudomonas aeruginosachromosome
Authors: Zhao Hang , Bhowmik Bijit , Rybenkov Valentin V.
Published: May 2020

Condensins are essential for global chromosome organization in diverse bacteria. Atypically,Pseudomonas aeruginosaencodes condensins from two superfamilies, SMC-ScpAB and MksBEF. We report that the two proteins play specialized roles in chromosome packing and segregation and are synthetically lethal with ParB. Inactivation of SMC or MksB asymmetrically affected global chromosome layout, its timing of segregation and sometimes triggered a chromosomal inversion. Localization pattern was also unique to each protein. SMC clusters colocalized withoriCthroughout cell cycle except shortly after origin duplication, whereas MksB clusters emerged at cell quarters shortly prior tooriCduplication and stayed there even after cell division. Relocation of the proteins was abrupt and coordinated withoriCdynamic. These data reveal that the two condensins asymmetrically play dual roles in chromosome maintenance by organizing it and mediating its segregation. Furthermore, the choreography of condensins andoriCrelocations suggest an elegant mechanism for the birth and maturation of chromosomes.

Importance

Mechanisms that define the chromosome as a structural entity remain unknown. A key element in this process are condensins, which globally organize chromosomes and contribute to their segregation. This study characterized condensin and chromosome dynamics inPseudomonas aeruginosa, which harbors condensins from two major protein superfamilies, SMC and MksBEF. The study revealed that both proteins asymmetrically play a dual role in chromosome maintenance by spatially organizing the chromosomes and guiding their segregation but can substitute for each other in some activities. The timing of chromosome, SMC and MksBEF relocation was highly ordered and interdependent revealing causative relationships in the process. Moreover, MksBEF was found to produce clusters at the site of chromosome replication that survived cell division and remained in place until chromosome replication was complete. Overall, these data delineate the functions of condensins from the SMC MksBEF superfamilies, reveal the existence of a chromosome organizing center and suggest a mechanism that might explain the biogenesis of chromosomes.
Modeling Human Peripheral Myelin Fully from Pluripotent Stem Cells and Immune-mediated NeuropathyIn Vitrousing ZIKA Virus
Authors: Mirakhori Fahimeh , Qin Cheng-Feng , Xu Zhiheng
Published: May 2020

The generation ofin vitromodel of human peripheral myelin development and associated disease from human pluripotent stem cells (hPSCs) has been a challenge so far. In addition, the underlying mechanism for ZIKA virus (ZIKV) infection incurred Guillain-Barré syndrome (GBS) remains unexplored due to the lack of a suitable model. Here, we report thede novogeneration of a human peripheral myelination model with competent Schwann cells (SCs). Those human SCs generated from hPSCs via compound screening were capable of forming compact myelin bothin vitroandin vivo. We found ZIKV infection caused GBS-like eventsin vitroincluding myelin sheath degeneration, as well as dysregulated transcriptional profile including the activated cell death pathways and cytokine production. These effects could be partially reversed by several pharmacological inhibitors. Our model therefore provides a new and robust tool for studying the pathogenic mechanisms and developing of therapeutic strategies for related neuropathies.
Comorbid chronic pain and depression: Shared risk factors and differential antidepressant effectiveness
Authors: Roughan William H. , Campos Adrián I. , García-Marín Luis M. , Cuéllar-Partida Gabriel , Lupton Michelle K. , Hickie Ian B. , Medland Sarah E. , Wray Naomi R. , Byrne Enda M. , Ngo Trung Thanh , Martin Nicholas G. , Rentería Miguel E.
Published: May 2020

The bidirectional relationship between depression and chronic pain is well recognized, but their clinical management remains challenging. Here we characterize the shared risk factors and outcomes for their comorbidity in the Australian Genetics of Depression cohort study (N=13,839). Participants completed online questionnaires about chronic pain, psychiatric symptoms, comorbidities, treatment response and general health. Logistic regression models were used to examine the relationship between chronic pain and clinical and demographic factors. Cumulative linked logistic regressions assessed the effect of chronic pain on treatment response for ten different antidepressants. Chronic pain was associated with an increased risk of depression (OR=1.86 [1.37–2.54]), recent suicide attempt (OR=1.88[1.14–3.09]), higher use of tobacco (OR=1.05 [1.02–1.09]) and misuse of painkillers (e.g., opioids; OR=1.31 [1.06–1.62]). Participants with comorbid chronic pain and depression reported fewer functional benefits from antidepressant use and lower benefits from sertraline (OR=0.75[0.68–0.83]), escitalopram (OR=0.75[0.67–0.85]) and venlafaxine (OR=0.78[0.68–0.88]) when compared to participants without chronic pain. Furthermore, participants taking sertraline (OR=0.45[0.30–0.67]), escitalopram (OR=0.45[0.27–0.74]) and citalopram (OR=0.32[0.15–0.67]) specifically for chronic pain (among other indications) reported lower benefits compared to other participants taking these same medications but not for chronic pain. These findings reveal novel insights into the complex relationship between chronic pain and depression. Treatment response analyses indicate differential effectiveness between particular antidepressants and poorer functional outcomes for these comorbid conditions. Further examination is warranted in targeted interventional clinical trials, which also include neuroimaging genetics and pharmacogenomics protocols. This work will advance the delineation of disease risk indicators and novel aetiological pathways for therapeutic intervention in comorbid pain and depression as well as other psychiatric comorbidities.
Shank2 expression identifies a subpopulation of glycinergic interneurons involved in nociception and altered in an autism mouse model
Authors: Heuvel Florian olde , Alami Najwa Ouali , Wilhelm Hanna , Deshpande Dhruva , Khatamsaz Elmira , Catanese Alberto , Woelfle Sarah , Schön Michael , Jain Sanjay , Grabrucker Stefanie , Ludolph Albert C. , Verpelli Chiara , Michaelis Jens , Boeckers Tobias M. , Roselli Francesco
Published: May 2020

Patients suffering from Autism Spectrum Disorders (ASD) experience disturbed nociception in form of either hyposensitivity to pain or hypersensitivity and allodynia. We have determined that Shank2-KO mice, which recapitulate the genetic and behavioural disturbances of ASD, display increased sensitivity to formalin pain and thermal, but not mechanical allodynia. We demonstrate that high levels of Shank2 expression identifies a subpopulation of neurons in murine and human dorsal spinal cord, composed mainly by glycinergic interneurons and that loss of Shank2 causes the decrease in NMDAR in excitatory synapses on these inhibitory interneurons. In fact, in the subacute phase of the formalin test, glycinergic interneurons are strongly activated in WT mice but not in Shank2-KO mice. As consequence, nociception projection neurons in lamina I are activated in larger numbers in Shank2-KO mice. Our findings prove that Shank2 expression identifies a new subset of inhibitory interneurons involved in reducing the transmission of nociceptive stimuli and whose unchecked activation is associated with pain hypersensitivity. Thus, we provide evidence that dysfunction of spinal cord pain processing circuits may underlie the nociceptive phenotypes in ASD patients and mouse models.
Hidden genomic features of an invasive malaria vector,Anopheles stephensi
Authors: Chakraborty Mahul , Ramaiah Arunachalam , Adolfi Adriana , Halas Paige , Kaduskar Bhagyashree , Ngo Luna Thanh , Jayaprasad Suvratha , Paul Kiran , Whadgar Saurabh , Srinivasan Subhashini , Subramani Suresh , Bier Ethan , James Anthony A. , Emerson J.J.
Published: May 2020

Background

The mosquitoAnopheles stephensiis a vector of urban malaria in Asia that recently invaded Africa. Studying the genetic basis of vectorial capacity and engineering genetic interventions are both impeded by limitations of a vector’s genome assembly. The existing assemblies ofAn. stephensiare draft-quality and contain thousands of sequence gaps, potentially missing genetic elements important for its biology and evolution.

Results

To access previously intractable genomic regions, we generated a reference-grade genome assembly and full transcript annotations that achieve a new standard for reference genomes of disease vectors. Here, we report novel species-specific transposable element families and insertions in functional genetic elements, demonstrating the widespread role of TEs in genome evolution and phenotypic variation. We discovered 29 previously hidden members of insecticide resistance genes, uncovering new candidate genetic elements for the widespread insecticide resistance observed inAn. stephensi. We identified 2.4 Mb of the Y-chromosome and seven new male-linked gene candidates, representing the most extensive coverage of the Y-chromosome in any mosquito. By tracking full length mRNA for >15 days following blood feeding, we discover distinct roles of previously uncharacterized genes in blood metabolism and female reproduction. The Y-linked heterochromatin landscape reveals extensive accumulation of long-terminal repeat retrotransposons throughout the evolution and degeneration of this chromosome. Finally, we identify a novel Y-linked putative transcription factor that is expressed constitutively through male development and adulthood, suggesting an important role throughout male development.

Conclusion

Collectively, these results and resources underscore the significance of previously hidden genomic elements in the biology of malaria mosquitoes and will accelerate development of genetic control strategies of malaria transmission.
Structural visualization of septum formation inStaphylococcus warneriusing atomic force microscopy
Authors: Su Hai-Nan , Li Kang , Yuan Xiao-Xue , Zhang Meng-Yao , Liu Si-Min , Chen Xiu-Lan , Liu Lu-Ning , Zhang Yu-Zhong
Published: May 2020

Cell division ofStaphylococcusadopts a “popping” mechanism that mediates extremely rapid separation of the septum. Elucidating the structure of the septum is crucial for understanding this exceptional bacterial cell division mechanism. Here, the septum structure ofStaphylococcus warneriis extensively characterized using high-speed time-lapse confocal microscopy, atomic force microscopy, and electron microscopy. The cells ofS. warneridivide in a fast “popping” manner on a millisecond timescale. Our results show that the septum is composed of two separable layers, providing a structural basis for the ultrafast daughter cell separation. The septum is formed progressively toward the center with non-uniform thickness of the septal disk in radial directions. The peptidoglycan on the inner surface of double-layered septa is organized into concentric rings, which are generated along with septum formation. Moreover, this study signifies the importance of new septum formation in initiating new cell cycles. This work unravels the structural basis underlying the “popping” mechanism that drivesStaphylococcuscell division and reveals a generic structure of the bacterial cell.

IMPORTRANCE

This work shows that the septum ofStaphylococcus warneriis composed of two layers and the peptidoglycan on the inner surface of the double-layered septum is organized into concentric rings. Moreover, new cell cycles ofStaphylococcuscould be initiated before the previous cell cycle is complete. This work advances our knowledge about a basic structure of bacterial cell and provides the double layered structural information of septum for the bacterium that divide with the “popping” mechanism.
The common chromosomal periodicity of transcriptomes is correlated with the bacterial growth rate
Authors: Nagai Motoki , Kurokawa Masaomi , Ying Bei-Wen
Published: May 2020

The growth rate, representing the fitness of a bacterial population, is determined by the whole transcriptome. Chromosomal periodicity is a representative overall feature of the whole transcriptome; however, whether and how it is associated with the bacterial growth rate are unknown. To address these questions, we analyzed a total of 213 transcriptomes of genetically differentiatedEscherichia colistrains growing in an assortment of culture conditions varying in terms of temperature, nutrition level and osmotic pressure. Intriguingly, the Fourier transform identified a common chromosomal periodicity of transcriptomes, which was independent of the variation in genomes and environments. In addition, fitting of the theoretical model found that the amplitudes of the periodic transcriptomes were significantly correlated with the growth rates. This novel finding successfully identified a single parameter representing the global pattern of the whole transcriptome for the first time and indicated that bacterial growth was correlated with the magnitude of chromosomal differentiation in gene expression. These results provided an alternative global parameter for evaluating the adaptiveness of a growing bacterial population and provided a quantitative rule that makes it possible to predict the growth dynamics according to the gene expression pattern.
Functional near-infrared spectroscopy in conjunction with electroencephalography of cerebellar transcranial direct current stimulation responses in the latent neurovascular coupling space – a chronic stroke study
Authors: Rezaee Zeynab , Ranjan Shashi , Solanki Dhaval , Bhattacharya Mahasweta , Srivastava MV Padma , Lahiri Uttama , Dutta Anirban
Published: May 2020

Cerebellar transcranial direct current stimulation (ctDCS) can facilitate motor learning; however, ctDCS effects have not been investigated using portable neuroimaging vis-à-vis lobular electric field strength. This is important since the subject-specific residual architecture for cerebellar interconnections with the cerebral cortex, including the prefrontal cortex (PFC) and the sensorimotor cortex (SMC), can influence the ctDCS effects on the cerebral functional activation. In this study, we investigated functional near-infrared spectroscopy (fNIRS) in conjunction with electroencephalography (EEG) to measure the changes in the brain activation at the PFC and the SMC following virtual reality (VR)-based Balance Training (VBaT), before and after ctDCS treatment in 12 hemiparetic chronic stroke survivors. Furthermore, we performed general linear modeling (GLM) that can putatively associate the lobular electric field strength due to ctDCS priming with the changes in the fNIRS-EEG measures in the chronic stroke survivors. Here, fNIRS-EEG based measures were investigated in their latent space found using canonical correlation analysis (CCA) that is postulated to capture neurovascular coupling. We found that the ctDCS electrode montage, as well as the state (pre-intervention, during intervention, post-intervention), had a significant (p<0.05) effect on the changes in the canonical scores of oxy-hemoglobin (O2Hb) signal measured with fNIRS. Also, skill acquisition during first exposure to VBaT decreased the activation (canonical score of O2Hb) of PFC of the non-lesioned hemisphere in the novices at their first exposure before the ctDCS intervention. Moreover, ctDCS intervention targeting the leg representation in the cerebellum led to a decrease in the canonical scores of O2Hb at the lesioned SMC, which is postulated to be related to the cerebellar brain inhibition. Furthermore, ctDCS electrode montage, as well as the state, had a significant (p<0.05) interaction effect on the canonical scores of log10-transformed EEG bandpower. Our current study showed the feasibility of fNIRS-EEG imaging of the ctDCS responses in the latent neurovascular coupling space that can not only be used for monitoring the dynamical changes in the brain activation associated with ctDCS-facilitated VBaT, but may also be useful in subject-specific current steering for tDCS to target the cerebral fNIRS-EEG sources to reduce inter-individual variability.
Repurposing beta3-adrenergic receptor agonists for Alzheimer’s disease: Beneficial effects on recognition memory and amyloid pathology in a mouse model
Authors: Tournissac Marine , Vu Tra-My , Vrabic Nika , Hozer Clara , Tremblay Cyntia , Mélançon Koralie , Planel Emmanuel , Pifferi Fabien , Calon Frédéric
Published: May 2020

Old age, the most important risk factor for Alzheimer’s disease (AD), is associated with thermoregulatory deficits. Brown adipose tissue (BAT) is the main thermogenic driver in mammals and its stimulation, through β3-adrenergic receptor (β3AR) agonists or cold acclimation, counteracts metabolic deficits in rodents and humans. Studies in animal models show that AD neuropathology leads to thermoregulatory deficits and cold-induced tau hyperphosphorylation is prevented by BAT stimulation through cold acclimation. Since metabolic disorders and AD share strong pathogenic links, we hypothesized that BAT stimulation through a β3AR agonist could exert benefits in AD as well.

Here, we show that β3AR agonist administration (CL-316,243, 1 mg/kg/day i.p., from 15 to 16 months of age) decreased body weight and improved peripheral glucose metabolism and BAT thermogenesis in both non-transgenic and 3xTg-AD mice. One-month treatment with a β3AR agonist increased recognition index by 19% in 16-month-old 3xTg-AD mice compared to pre-treatment (14-month-old). Locomotion, anxiety and tau pathology were not modified. Finally, insoluble Aβ42/Aβ40 ratio was decreased by 27% in the hippocampus of CL-316,243-injected 3xTg-AD mice.

Overall, our results indicate that β3AR stimulation reverses memory deficits and shifts downward the insoluble Aβ42/Aβ40 ratio in 16-month-old 3xTg-AD mice. As β3AR agonists are being clinically developed for metabolic disorders, repurposing them in AD could be a valuable therapeutic strategy.
Why do academics become entrepreneurs? How do their motivations evolve? Results from an empirical study
Authors: Galati Francesco , Bigliardi Barbara , Passaro Renato , Quinto Ivana
Published: May 2020

Purpose

According to the paradigm of the Triple Helix, universities are moving from their traditional roles of research, teaching and knowledge dissemination to an entrepreneurial role. Specifically, they contribute to innovation and competitiveness by creating academic spin-offs (ASOs). In such a context, the diffusion of digital technologies is impacting both on the development of new forms of academic entrepreneurship and on the motivations of academics in launching ASOs. Grounded on a recent reconceptualization developed on identity theory, this study investigates the motivations that lead an academic to establish a spin-off and if, how and why these motivations vary over time.

Design/methodology/approach

An extensive online survey was performed in order to obtain a final database of 151 Italian ASOs. Different statistical techniques were used, such as Cluster analysis and ANOVA, to identify different ASO profiles and to understand how and why these profiles change over time.

Findings

The results suggest that motivations change over time: while financial aspects become less important, academics give more importance to other issues. Time, experience and financial gain influence the evolution of academic entrepreneurs' motivations over time.

Practical implications

Insights derived from the study could help policy-makers and administrators in better understanding this phenomenon and the possible evolution of such academic motivations in the context of digitalization, and enable them to act accordingly to foster academic entrepreneurship.

Originality/value

The main contributions of the present study are the addition of empirical knowledge to the scant and anecdotal literature existing to date and the inclusion of cognitive and psychological theoretical perspectives in the academic entrepreneurship debate. Moreover, it is believed that no other study has investigated the above topics in the Italian context.
The rise in the numbers of pupils identified by schools with autism spectrum disorder (ASD): a comparison of the four countries in the United Kingdom
Authors: McConkey Roy
Published: May 2020

An annual school census is held in the four countries of the UK in which pupils with ASD are identified. This longitudinal study of the total UK school population compares increases in prevalence rates for pupils with ASD over a nine‐year period from 2010/11. Northern Ireland had the highest prevalence throughout, reaching 3.20% by 2018/19 compared to 1.92% in Wales. The prevalence rates were higher in secondary than in primary schools. The increases in prevalence and intra‐country variations may be linked to a greater appreciation of ASD occurring alongside other developmental difficulties. Greater reliance on school rather than statutory assessments may also contribute to increases in pupils with ASD. More in‐depth research is needed to establish the reason for the variations across years and countries.
Developing students' mental health literacy through the power of sport
Authors: Glazzard Jonathan , Szreter Ben
Published: May 2020

This research is an evaluation of a six‐week mental health literacy programme, referred to as the Cambridge United Community Trust’s ‘Mind Your Head’ programme, which was delivered by sports professionals to secondary school students (11‐16) in Cambridge, England, during 2017–18. A Mental Health Literacy Scale was used to measure students’ knowledge of mental health issues pre‐ and post‐intervention. Statistical data from these surveys were analysed using an independent samples t‐test. Focus groups were held with students in each school, and individual semi‐structured interviews were conducted with one lead teacher in each school. The statistical data indicate that statistically significant improvements in mental health literacy were achieved, and this occurred across all genders and ethnicities. The qualitative data suggest that this programme resulted in positive attitudes towards mental health and improved knowledge of how to seek help. The data indicate that investment in similar programmes would be beneficial for schools in improving students’ knowledge of mental health and reducing stigma.
Optimization of ultrasonic‐assisted extraction conditions for bioactive components from coffee leaves using the Taguchi design and response surface methodology
Authors: Chen Xiumin , Ding Jian , Ji Dayi , He Suqun , Ma Haile
Published: May 2020

Coffee leaves contain various bioactive compounds that are beneficial for human health. However, there are very limited researches related to the extraction of the bioactive phytochemicals from coffee leaves. In the present study, the extraction conditions for bioactive components from coffee leaves were optimized using Taguchi design and response surface methodology (RSM). Taguchi design was used to screen significant factors that affected the yield of phytochemicals including trigonelline, caffeine, chlorogenic acids, mangiferin, and rutin, total phenolic content (TPC) and antioxidant activity. Sequentially, a Box‐Behnken design (BBD) was used to optimize the extraction conditions. Three factors including Liquid‐to‐solid (L:S) ratio, ethanol concentration, and extraction temperature that significantly affected most of the phytochemical yields and antioxidant activity were selected from the six variables using Taguchi design. The optimal extraction conditions obtained from RSM were 30.3:1 L:S ratio, 54.5% ethanol, and 80 °C when simultaneously considered four responses, including TPC, the yields of mangiferin and 5‐CQA and DPPH scavenging capacity. Under the optimal conditions, the experimental results for the above four responses were 62.1 mg gallic acid/g, 4.1 mg/g, 11.4 mg/g, and 356.9 µmol Trolox/g, respectively, which were close to the predicted values. About 97% of phytochemicals can be extracted in the first two times of extraction. In conclusion, the combination of Taguchi design and response surface methodology can be successfully used to screen and optimize the significant factors that affected the bioactive components extracted from coffee leaves.

Practical Application

Coffee leaves, the byproducts of coffee plants, are considered no‐ or low‐value although it has a long history for using them as tea‐like beverage and ethnomedicine by locals in the coffee plant growing countries. Bioactive components extracted from coffee leaves can be used as ingredients in functional beverages, functional food, and natural health products. These applications will add values to coffee leaves as well as increase the incomes of coffee farmers and workers.
Relative humidity–temperature transition boundaries for anhydrous β‐caffeine and caffeine hydrate crystalline forms
Authors: Allan Matthew C. , Owens Bridget , Mauer Lisa J.
Published: May 2020

Caffeine is a hydrate‐forming polymorphic crystalline compound that can exist in α, β, and hydrate forms. Phase transitions between hydrate and anhydrous forms of a crystalline ingredient, and related water migration, can create product quality challenges. The objective of this study was to determine the relative humidity (RH)–temperature phase boundary between anhydrous β‐caffeine and caffeine hydrate. The β‐caffeine→caffeine hydrate and caffeine hydrate→β‐caffeine RH–temperature transition boundaries were determined from 20 to 45 °C using a combination of water activity (aw) controlled solution and vapor‐mediated equilibration, moisture sorption, powder X‐ray diffraction, and Fourier‐transform infrared spectroscopy techniques. Two transition boundaries were measured: the β‐caffeine→caffeine hydrate transition boundary (0.835 ± 0.027 aw at 25 °C) was higher than the caffeine hydrate→β‐caffeine transition boundary (0.625 ± 0.003 aw at 25 °C). Moisture sorption rates for β‐caffeine, even at high RHs (>84% RH), were slow. However, caffeine hydrate rapidly dehydrated at low RHs (<30% RH) into a metastable transitional anhydrous state with a similar X‐ray diffraction pattern to metastable α‐caffeine. Exposing this dehydrated hydrate to higher RHs (>65% RH) at lower temperatures (20 to 30 °C) resulted in full restoration to a 4/5 caffeine hydrate. This transitional anhydrous state was unstable and converted to a less hygroscopic state after annealing at 50 °C and 0% RH for 1 day. It was postulated that the caffeine hydrate→β‐caffeine was the true β‐caffeine↔caffeine hydrate phase boundary and that β‐caffeine could be metastable above the caffeine hydrate→β‐caffeine transition boundary. These caffeine RH–temperature transition boundaries could be used for selecting formulation and storage conditions to maintain the desired caffeine crystalline form.

Practical Application

Caffeine can exist as either an anhydrous (without water) or hydrate (internalized water) crystalline state. The stability of each caffeine crystalline form is dictated by humidity (or water activity) and temperature, and these environmental stability boundaries for the caffeine crystalline forms are reported in this manuscript. Conversions between the two crystalline states can lead to deleterious effects; for example, the presence of caffeine hydrate crystals in a low water activity food (e.g., powder) could lead to the relocation of the water in caffeine to other ingredients in the food system, leading to unwanted water–solid interactions that could cause clumping and/or degradation.
Assessing consumers’ understanding of the term “Natural” on food labeling
Authors: Rahman Sajida , Zasadzinski Lindsay , Zhu Lanjun , Edirisinghe Indika , Burton‐Freeman Britt
Published: May 2020

The objective of this study was to gain a better understanding of how consumers’ interpret the term “natural” by assessing food choice based on labels describing attributes of a product associated with the term “natural”; to assess food intake of chosen food, and; to determine factors that influence food choice and intake. A randomized, single‐visit pilot study was conducted where participants (n = 105) were presented with seven identical bowls of granola each bearing a different descriptive label. Participants were asked to choose and eat the granola (ad libitum) that coincided with what was closest to their view of “natural.” Food choice, intake amount, demographics, self‐health perception, label use, dietary restraint, and mindfulness were measured. “Organic” (31%), “Made with real grains” (17%), and “No preservatives” (15%) were the top three chosen labels. These choices related to concerns about environment and processing, personal health, and additives and preservatives, respectively (P = 0.049). Income level and age were significantly associated with choice (P = 0.003). Defining the term “natural” for use on food labels will require follow‐up researchacrosseconomically diverse populations and age groups to understand expectations of food products bearing the term “natural.”
Prostate penile metastasis: Incidence and imaging pattern on 68Ga‐PSMA PET/CT
Authors: Tatkovic Annaleis , McBean Rhiannon , Schoeman Joseph , Wong David
Published: May 2020

Background

Prostate cancer commonly metastasises to bone and regional lymphatics and more rarely to locations such as the brain, skin and penis. Gallium‐68 prostate‐specific membrane antigen (68Ga‐PSMA) positron emission tomography/computed tomography (PET/CT) has widely become the routine imaging modality for prostate cancer staging and re‐staging in Australia. The aim of this study was to retrospectively review all 68Ga‐PSMA PET/CT examinations performed to date at our institution to determine the frequency of penile metastases.

Methods

A total of 4860 68Ga‐PSMA PET/CT examinations were performed between 16/07/2014 and 31/10/2019. Radiology reports for each examination were filtered to identify those with the words ‘penis’ or ‘penile’. Once identified, relevant reports and images were individually reviewed to confirm the presence of a PSMA‐avid penile lesion.

Results

The incidence of penile metastasis of prostate cancer observed in this study was 0.1% with six examinations identified as having PSMA‐avid penile lesions in five prostate cancer patients (age range: 71–88 years). The patients had a 1–8 year history of prostate cancer with varying severity of disease. Appearance of PSMA‐avidity varied between single focal lesion, multiple focal lesions and diffuse lesion.

Conclusions

An incidence of 0.1% in our study confirms the rarity of penile metastases of prostate cancer. Although rare, identification of prostate cancer penile metastases is important for appropriate treatment management and symptom‐relief.
Letter: are microbes other than Helicobacter pylori associated with gastric cancer?
Authors: He Cong , Peng Chao , Xia Zhongkui , Lu Nonghua
Published: May 2020

LINKED CONTENT

This article is linked to Gantuya et al papers. To view these articles, visit https://doi.org/10.1111/apt.15675 and https://doi.org/10.1111/apt.15757.
Letter: golimumab efficacy in patients with Crohn's disease and concomitant severe arthritis
Authors: Miceli Maria Concetta , Arcuri Chiara , Renna Sara , Orlando Ambrogio , Provenzano Giuseppe
Published: May 2020

LINKED CONTENT

This article is linked to Martineau et al paper. To view this article, visit https://doi.org/10.1111/apt.14371.
Exercise training as prophylactic strategy in the management of neutropenia during chemotherapy
Authors: Schauer Tim , Hojman Pernille , Gehl Julie , Christensen Jesper Frank
Published: May 2020

Chemotherapy‐induced immune‐suppression is a common, but potential detrimental, adverse reaction in patients undergoing treatment for cancer and strategies with capacity to boost the immune cell populations are needed. Physical exercise training is a potent regulator of immune cell viability and function and may serve as a viable, non‐pharmacological prophylactic strategy in addition to the current pharmacological management by, for example, granulocyte‐colony stimulating factor (G‐CSF). Here, we review the mechanistic evidence linking exercise training to haematopoietic function and subsequent possible amelioration of chemotherapy‐related neutropenia. First, we briefly describe neutrophil regulation and management of neutropenia in cancer patients. Second, we summarize the effect of acute and chronic exercise training on neutrophils and their progenitors, and finally, we outline the current clinical evidence of exercise interventions in ongoing anti‐cancer treatment in regard to neutropenia incidence, treatment tolerance and related outcomes.

LINKED ARTICLES

This article is part of a themed issue on New avenues in cancer prevention and treatment (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.12/issuetoc