bluuebunny/crossref_metadata_2025 huggingface dataset:
A dynamic template complex mediates Munc18-chaperoned SNARE assembly
Authors: Yang Jie , Jin Huaizhou , Liu Yihao , Guo Yaya , Zhang Yongli
Published: December 2022

Munc18 chaperones assembly of three membrane-anchored soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) into a four-helix bundle to mediate membrane fusion between vesicles and plasma membranes, leading to neurotransmitter or insulin release, glucose transporter (GLUT4) translocation, or other exocytotic processes. Yet, the molecular mechanism underlying chaperoned SNARE assembly is not well understood. Recent evidence suggests that Munc18-1 and Munc18-3 simultaneously bind their cognate SNAREs to form ternary template complexes – Munc18-1:Syntaxin-1:VAMP2 for synaptic vesicle fusion and Munc18-3:Syntaxin-4:VAMP2 for GLUT4 translocation and insulin release, which facilitate the binding of SNAP-25 or SNAP-23 to conclude SNARE assembly. Here, we further investigate the structure, dynamics, and function of the template complexes using optical tweezers. Our results suggest that the synaptic template complex transitions to an activated state with a rate of 0.054 s
−1
for efficient SNAP-25 binding. The transition depends upon the linker region of syntaxin-1 upstream of its helical bundle-forming SNARE motif. In addition, the template complex is stabilized by a poorly characterized disordered loop region in Munc18-1. While the synaptic template complex efficiently binds both SNAP-25 and SNAP-23, the GLUT4 template complex strongly favors SNAP-23 over SNAP-25, despite the similar stabilities of their assembled SNARE bundles. Together, our data demonstrate that a highly dynamic template complex mediates efficient and specific SNARE assembly.
Standard-ness, national ideologies and their embedding in ‘sociolinguistic theory’
Authors: Satyanath Shobha
Published: December 2022

In spite of the centrality of the vernacular in sociolinguistics, we find, it is constantly pitched against the standard, failing to make meaning on its own. It is common practice in western sociolinguistics to identify variants as standard or non-standard, thus marking a distinction between the two and their social meanings. However, when researching English in non-western contexts, such a distinction may not always be tenable. This study reports on variation in the use of a pre-verbal auxiliary – derived from English periphrastic Do – in the speech of Indo-Guyanese speakers, a community of Indian descent in Guyana. A series of matched guise tests were conducted which suggest confusion in the minds of speakers in unambiguously labeling the variants as English, creole or mixed. Further, auxiliary variants are evaluated neutrally without attaching greater or lesser value or prestige in spite of an on-going change at an advanced stage. This has consequences for the very notions of standard and standard-ness, which continue to dominate sociolinguistic modelling of variation in western contexts.
Who’s reading who?
Authors: Quinn Marie
Published: December 2022

The phenomenon of English ‘colonising’ academic publishing had been observed globally, so that English-speaking academics rarely need to venture into non-English texts in order to build new knowledge. In the case of research in the education and language fields in Timor-Leste, academic research and writing appears predominantly in Portuguese, with English as a significant second language of research. In this case, researchers need to engageacrossthese dominant languages in order to draw on the accumulated research and knowledge about contexts where research is carried out. Not engaging with both these languages, and other local languages, risks building incomplete knowledge of the Timorese context.

This paper presents the results of a citation analysis of academic research items written between 1999 and 2020. Findings indicate that working only within a particular language is frequent among researchers writing in either Portuguese or English, often ignoring research in the other dominant languages and in local languages. This study suggests that researchers within multilingual countries need to read widely, considering a range of languages and sources. It also suggests the ways in which technological tools might help alleviate some of the barriers to inter-language communication around research.
A novel exponential degradation approach for predicting the remaining useful life of roadheader bearings
Authors: Liu Qiang , Liu Songyong , Dai Qianjin , Cui Yuming , Xie Qizhi
Published: December 2022

Based on the optimized exponential-degradation model (OEDM), a novel approach for predicting the remaining useful life(RUL) of roadheader bearings under different working conditions is proposed in this study. Specifically, the exponential process is used to construct the degradation process from a single performance characteristic under variable operating conditions, the generalized expectation maximization is employed to estimate model parameters, and the proposed degradation model is updated after new data is available. In the traditional exponential degradation method, the hyperparameters are only optimized, which leads to low calculation accuracy under severe working conditions. In the proposed method, the Bayesian algorithm and the Drift Brownian motion algorithm were respectively employed to optimize hyperparameters and stochastic parameters to ensure the high accuracy of the prediction results. In addition, degradation characteristics combined with sensory data acquired through condition monitoring were used to continuously update the RUL in the proposed degradation model. Finally, the effectiveness of the proposed model is verified by a simulation case and a case study. The results show that compared with the linear degradation model and the general exponential degradation model, the proposed OEDM performs well in practical applications and has a higher prediction accuracy. This study provides a reference for predictive maintenance of critical parts of tunneling machinery and cost reduction of tunneling.
Personality predicts mode of attack in a generalist ground spider predator
Authors: Beydizada Narmin , Pekár Stano
Published: December 2022

Personality traits, such as boldness and/or aggressiveness, have long been accepted to have a profound influence on many aspects of the lives of animals, including foraging. However, little is known about how personality traits shape the use of a particular attack strategy. Ground spiders use either venom or silk attack to immobilize prey. In this study, we tested the hypothesis that behavioral differences among individuals (namely boldness, measured as the time spent exploring a novel environment; and aggressiveness, measured as the number of killed but not consumed prey) drive the use of a particular attack strategy. We used a generalist ground spider, Drassodes lapidosus, and recorded the mode of attack on two types of prey, dangerous and safe. Moreover, we measured the size of the venom gland to test the relationship between the size of venom volume and the personality, as well as the mode of attack. Drassodes individuals showed consistent behavioral differences in the way they attacked prey. Venom attack was significantly related to increased aggressiveness when attacking spider (dangerous) prey and to increased boldness when attacking cricket (safe) prey. Silk attack was more frequently used by shy (for cricket prey) and docile (for spider prey). The volume of venom was not related to the attack strategy. We conclude that personality traits are important drivers of prey-capture behavior in generalist ground spiders.
Longitudinal regression of covariance matrix outcomes
Authors: Zhao Yi , Caffo Brian S , Luo Xi
Published: December 2022

In this study, a longitudinal regression model for covariance matrix outcomes is introduced. The proposal considers a multilevel generalized linear model for regressing covariance matrices on (time-varying) predictors. This model simultaneously identifies covariate-associated components from covariance matrices, estimates regression coefficients, and captures the within-subject variation in the covariance matrices. Optimal estimators are proposed for both low-dimensional and high-dimensional cases by maximizing the (approximated) hierarchical-likelihood function. These estimators are proved to be asymptotically consistent, where the proposed covariance matrix estimator is the most efficient under the low-dimensional case and achieves the uniformly minimum quadratic loss among all linear combinations of the identity matrix and the sample covariance matrix under the high-dimensional case. Through extensive simulation studies, the proposed approach achieves good performance in identifying the covariate-related components and estimating the model parameters. Applying to a longitudinal resting-state functional magnetic resonance imaging data set from the Alzheimer’s Disease (AD) Neuroimaging Initiative, the proposed approach identifies brain networks that demonstrate the difference between males and females at different disease stages. The findings are in line with existing knowledge of AD and the method improves the statistical power over the analysis of cross-sectional data.
‘Is Gold Dust to My Mind’: Exploring Lived Experience in Social Work Education
Authors: Howells Aisha , Walters Sophie , Duckett Nora , Barker Sarah , Clarke-Emmerson Steve , Darke Jane , Johnson Carol , Meggs Chris , Reeve Sebastian
Published: December 2022

The involvement of people with lived experience (service participants) is mandatory within UK social work education, although the form this takes varies significantly between organisations. This article outlines the final phase of a two-year research project focused on understanding the mechanisms which support and develop the meaningful and sustainable involvement of people with lived experience in social work education within a Higher Education Institution and a Local Authority Teaching Partnership in the East of England. The research team worked collaboratively using co-production principles and possessed lived experience backgrounds. This article presents findings from a qualitative study using interviews and questionnaires that aimed to deepen understanding of the concept and practice of embedding lived experience in social work education. Thematic analysis identified a dedicated role with the motivation and drive to achieve sustained inclusion in creative ways was the underpinning of meaningful and sustainable lived experience involvement. This was alongside opportunities to shape diverse and relational learning experiences, values reflecting compassionate and respectful relationships, and power sharing, accompanied by practical resources, can create a culture change. Together, these principles, practices and values have been instrumental in creating meaningful and sustainable lived experience involvement within social work education.
Postnatal development of electrophysiological and morphological properties in layer 2/3 and layer 5 pyramidal neurons in the mouse primary visual cortex
Authors: Ciganok-Hückels Natalja , Jehasse Kevin , Kricsfalussy-Hrabár Lena , Ritter Mira , Rüland Thomas , Kampa Björn M
Published: December 2022

Eye-opening is a critical point for laminar maturation of pyramidal neurons (PNs) in primary visual cortex. Knowing both the intrinsic properties and morphology of PNs from the visual cortex during development is crucial to contextualize the integration of visual inputs at different age stages. Few studies have reported changes in intrinsic excitability in these neurons but were restricted to only one layer or one stage of cortical development. Here, we used in vitro whole-cell patch-clamp to investigate the developmental impact on electrophysiological properties of layer 2/3 and layer 5 PNs in mouse visual cortex. Additionally, we evaluated the morphological changes before and after eye-opening and compared these in adult mice. Overall, we found a decrease in intrinsic excitability in both layers after eye-opening which remained stable between juvenile and adult mice. The basal dendritic length increased in layer 5 neurons, whereas spine density increased in layer 2/3 neurons after eye-opening. These data show increased number of synapses after onset of sensory input paralleled with a reduced excitability, presumably as homeostatic mechanism. Altogether, we provide a database of the properties of PNs in mouse visual cortex by considering the layer- and time-specific changes of these neurons during sensory development.
Employees’ reaction to gender pay transparency: an online experiment
Authors: Baggio Marianna , Marandola Ginevra
Published: December 2022

The primary aim of pay transparency measures is to make pay systems less opaque and to reduce the gender pay gap. To investigate the behavioural implications of pay transparency measures, we ran an incentivized online experiment focused on the effects on employees’ performance, provision of extra effort and actions to correct pay disparities. We found that overall pay transparency does not disrupt employees’ performance. However, by revealing relative wages, it does interfere with the provision of effort and extra effort of employees with a below-average wage. Moreover, we found that pay transparency increased potentially justified requests to correct pay disparities while decreasing unjustified requests. Our evidence also shows that employee’s effort and action against unfair pay are more sensitive to lower relative wage with respect to own gender, rather than the other gender. We discuss potential policy implications of these findings and argue that more research should be carried out to better understand the efficiency of transparency measures, with a particular focus on gender reference groups.
Postwar Italian Journeys: Narratives of Homecoming, National Cohesion and German–Italian Friendship
Authors: Hanshew Karrin
Published: December 2022

Scholars, journalists, diplomats and even archivists routinely assert that to understand German–Italian relations one must start with Goethe. Without denying Goethe’s importance, this article suggests that the emotional pull and prominence of Italy for postwar Germans may have had less to do with Goethe than with the Italian journey’s importance as a shared script. By providing familiar sets of baseline behaviours and roles on which Italians and Germans could rely and to which they could attune their expectations, the script of the Italian journey helped smooth postwar tensions. It eased early West German travels and the pangs of national division, and for a time it also worked to salve Italians’ own national wounds, in addition to bringing in much-needed tourist revenues. As a framework for social interaction, moreover, the Italian journey helped both Italians and Germans work around their complex relations and uncomfortable pasts. That it lives on as an explanation for foreign relations and a popular trope also points to the tradition’s reinvention in the postwar period and its distance from the historical referent. The location of the Italian journey in the eighteenth century and the timeless quality that this long history gave to Germans’ yearning for Italy continued to offer postwar Germans a claim to national cohesion. It served (theoretically) to unite, first, West Germans and then, after 1990, Germans east and west. As a salvageable national tradition, it had few competitors.
Clinical and functional characterization of germline PIK3CA variants in patients with PIK3CA-related overgrowth spectrum disorders
Authors: Cooley Coleman Jessica A , Gass Jennifer M , Srikanth Sujata , Pauly Rini , Ziats Catherine A , Everman David B , Skinner Steven A , Bell Shannon , Louie Raymond J , Cascio Lauren , Patterson Wesley G , Jones Julie R , Di Donato Nataliya , Stevenson Roger E , Boccuto Luigi
Published: December 2022

Mosaic variants in the PIK3CA gene, encoding the catalytic subunit of phosphoinositide 3-kinase (PI3K), produce constitutive PI3K activation, which causes PIK3CA-related overgrowth spectrum disorders. To date, fewer than 20 patients have been described with germline alterations in PIK3CA. In this study, we describe three unrelated individuals with overgrowth and germline PIK3CA variants. These variants were discovered through whole-exome sequencing and confirmed as germline by testing multiple tissue types, when available. Functional analysis using Patient 1’s fibroblast cell line and two previously reported patients’ cell lines showed increased phosphorylation of AKT during cellular starvation revealing constitutive activation of the phosphoinositide-3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/AKT/mTOR) pathway. Alternatively, stimulation of the cells by fetal bovine serum produced a reduced response, indicating an activated status of the PI3K complex reducing the pathway response to further external stimulation. Additional studies utilizing Biolog Phenotype Microarray technology indicated reduced energy production when cells were exposed to growth factors stimulating the PI3K/AKT/mTOR pathway, confirming the trend observed in the AKT phosphorylation test after stimulation. Furthermore, treatment with inhibitors of the PI3K/AKT/mTOR pathway rescued the normal energy response in the patients’ cells. Collectively, these data demonstrate that disease-causing germline PIK3CA variants have a functional consequence, similar to mosaic variants in the PI3K/AKT/mTOR pathway.
Foreseeing the future of Posidonia oceanica meadows by accounting for the past evolution of the Mediterranean Sea
Authors: Martínez-Abraín Alejandro , Castejón-Silvo Inés , Roiloa Sergio
Published: December 2022

The current warming of the Mediterranean Sea has been forecast to lead to the shrinkage of seagrass meadows. We agree that rising sea temperatures most likely will have immediate negative effects on them because present-day asexually reproducing clones of Posidonia oceanica were likely selected as a form of resistance under suboptimal conditions during the colder temperatures of the last glaciation. However, since the evolution of P. oceanica has happened under tropical/subtropical conditions for tens of millions of years, some kind of evolutionary resilience to high temperatures is to be expected. We suggest that the ability of P. oceanica plants to reproduce sexually when water temperature is >27°C might lead in the future to the selection of warm-loving plants (as warm-sensitive clones decline), with an associated increase in genetic variability in the species gene pool. Predictions focused exclusively on the future decline of cold-selected (warm-sensitive) clones may result in short-sighted forecasts because the deep history of the taxon is overlooked. We suggest that an evolutionary-based approach should be more often considered when analysing the present declines of animal and plant species. We provide some additional examples of cases in which this could be done.
Nothing to Lose but Their Restraints of Trade: Lessons for Employment Non-Compete Clauses from EU Competition Law
Authors: Mcmahon Christopher , Eustace Alan
Published: December 2022

Courts on both sides of the Irish Sea have handed down significant judgments in the field of post-employment restrictive covenants in recent years. This article argues that these cases expose the common law rules on restraint of trade as fundamentally inadequate for regulating non-compete clauses in the modern economy. Ultimately, the scope of these restrictive covenants can only be determined by examining the nature of the relevant market and defining the previous employer’s competitors. This article argues that courts should make full use of methods developed by EU competition law to define the limits of the relevant market, identify the competitors of the previous employer and assess the scale of the restraint. Although this method cannot fully determine the reasonableness of a non-compete clause, it would lead to more effective and systematic treatment of non-compete clauses that considerably improves upon the pragmatic and incompletely theorised approach currently taken by courts in both Ireland and the UK.
A common transcriptional mechanism involving R-loop and RNA abasic site regulates an enhancer RNA of APOE
Authors: Watts Jason A , Grunseich Christopher , Rodriguez Yesenia , Liu Yaojuan , Li Dongjun , Burdick Joshua T , Bruzel Alan , Crouch Robert J , Mahley Robert W , Wilson Samuel H , Cheung Vivian G
Published: December 2022

RNA is modified by hundreds of chemical reactions and folds into innumerable shapes. However, the regulatory role of RNA sequence and structure and how dysregulation leads to diseases remain largely unknown. Here, we uncovered a mechanism where RNA abasic sites in R-loops regulate transcription by pausing RNA polymerase II. We found an enhancer RNA, AANCR, that regulates the transcription and expression of apolipoprotein E (APOE). In some human cells such as fibroblasts, AANCR is folded into an R-loop and modified by N-glycosidic cleavage; in this form, AANCR is a partially transcribed nonfunctional enhancer and APOE is not expressed. In contrast, in other cell types including hepatocytes and under stress, AANCR does not form a stable R-loop as its sequence is not modified, so it is transcribed into a full-length enhancer that promotes APOE expression. DNA sequence variants in AANCR are associated significantly with APOE expression and Alzheimer's Disease, thus AANCR is a modifier of Alzheimer's Disease. Besides AANCR, thousands of noncoding RNAs are regulated by abasic sites in R-loops. Together our data reveal the essentiality of the folding and modification of RNA in cellular regulation and demonstrate that dysregulation underlies common complex diseases such as Alzheimer's disease.
Recognition of 5-methyl-CG and CG base pairs in duplex DNA with high stability using antiparallel-type triplex-forming oligonucleotides with 2-guanidinoethyl-2′-deoxynebularine
Authors: Notomi Ryotaro , Sasaki Shigeki , Taniguchi Yosuke
Published: December 2022

The formation of triplex DNA is a site-specific recognition method that directly targets duplex DNA. However, triplex DNA formation is generally formed for the GC and AT base pairs of duplex DNA, and there are no natural nucleotides that recognize the CG and TA base pairs, or even the 5-methyl-CG (5mCG) base pair. Moreover, duplex DNA, including 5mCG base pairs, epigenetically regulates gene expression in vivo, and thus targeting strategies are of biological importance. Therefore, the development of triplex-forming oligonucleotides (TFOs) with artificial nucleosides that selectively recognize these base pairs with high affinity is needed. We recently reported that 2′-deoxy-2-aminonebularine derivatives exhibited the ability to recognize 5mCG and CG base pairs in triplex formation; however, this ability was dependent on sequences. Therefore, we designed and synthesized new nucleoside derivatives based on the 2′-deoxy-nebularine (dN) skeleton to shorten the linker length connecting to the hydrogen-bonding unit in formation of the antiparallel motif triplex. We successfully demonstrated that TFOs with 2-guanidinoethyl-2′-deoxynebularine (guanidino-dN) recognized 5mCG and CG base pairs with very high affinity in all four DNA sequences with different adjacent nucleobases of guanidino-dN as well as in the promoter sequences of human genes containing 5mCG base pairs with a high DNA methylation frequency.
Implementing re-configurable biological computation with distributed multicellular consortia
Authors: Canadell David , Ortiz-Vaquerizas Nicolás , Mogas-Diez Sira , de Nadal Eulàlia , Macia Javier , Posas Francesc
Published: December 2022

The use of synthetic biological circuits to deal with numerous biological challenges has been proposed in several studies, but its implementation is still remote. A major problem encountered is the complexity of the cellular engineering needed to achieve complex biological circuits and the lack of general-purpose biological systems. The generation of re-programmable circuits can increase circuit flexibility and the scalability of complex cell-based computing devices. Here we present a new architecture to produce reprogrammable biological circuits that allow the development of a variety of different functions with minimal cell engineering. We demonstrate the feasibility of creating several circuits using only a small set of engineered cells, which can be externally reprogrammed to implement simple logics in response to specific inputs. In this regard, depending on the computation needs, a device composed of a number of defined cells can generate a variety of circuits without the need of further cell engineering or rearrangements. In addition, the inclusion of a memory module in the circuits strongly improved the digital response of the devices. The reprogrammability of biological circuits is an intrinsic capacity that is not provided in electronics and it may be used as a tool to solve complex biological problems.
Transcription elongator SPT6L regulates the occupancies of the SWI2/SNF2 chromatin remodelers SYD/BRM and nucleosomes at transcription start sites in Arabidopsis
Authors: Shu Jie , Ding Ning , Liu Jun , Cui Yuhai , Chen Chen
Published: December 2022

Chromatin remodelers have been thought to be crucial in creating an accessible chromatin environment before transcription activation. However, it is still unclear how chromatin remodelers recognize and bind to the active regions. In this study, we found that chromatin remodelers SPLAYED (SYD) and BRAHMA (BRM) interact and co-occupy with Suppressor of Ty6-like (SPT6L), a core subunit of the transcription machinery, at thousands of the transcription start sites (TSS). The association of SYD and BRM to chromatin is dramatically reduced in spt6l and can be restored mainly by SPT6LΔtSH2, which binds to TSS in a RNA polymerase II (Pol II)-independent manner. Furthermore, SPT6L and SYD/BRM are involved in regulating the nucleosome and Pol II occupancy around TSS. The presence of SPT6L is sufficient to restore the association of the chromatin remodeler SYD to chromatin and maintain normal nucleosome occupancy. Our findings suggest that the two chromatin remodelers can form protein complexes with the core subunit of the transcription machinery and regulate nucleosome occupancy in the early transcription stage.
The Complex Association of Daily Opioid Dose with Visits for Pain in Sickle Cell Disease: Tolerance or Treatment-Refractory Pain?
Authors: Prince Elizabeth J , Pecker Lydia H , Lanzkron Sophie , Carroll C Patrick
Published: December 2022

Introduction

Opioids are used for acute and chronic pain in patients with sickle cell disease. How outpatient opioid regimens relate to acute care visits is of interest given the risks of high opioid doses and high hospital utilization. A prior study by our group suggested that outpatient opioid treatment for chronic pain could contribute to a vicious cycle of treatment-refractory acute pain, greater acute care utilization, and escalating opioid doses. The present larger naturalistic observational study was undertaken to determine whether the results were reliable across multiple acute care settings.

Methods

One year of clinical data on patients (n = 291) followed in the Sickle Cell Center for Adults (August 2018 to July 2019) were extracted, including visits to the emergency department, visits to the infusion center, and inpatient admissions. Outpatient opioid dosage was used to predict acute care treatment in generalized linear models that were controlled for patient, disease, and treatment characteristics.

Results

Outpatient opioid dosage predicted dosage during visits but did not predict visit length or pain relief. Higher outpatient opioid dosage was associated with greater number of visits. However, in post hoc analyses, this relationship was nonlinear, with a clear positive association only for those prescribed the lowest 50% of dosages.

Discussion

Higher outpatient opioid dosage predicted higher dosages during acute care visits to achieve the same pain score improvement, which is more consistent with opioid tolerance than with treatment-refractory pain. The relationship of outpatient opioid dosage with number of acute care visits was more complex, which suggests that opioid consumption at lower levels is driven by intermittent acute pain and opioid consumption at higher levels is driven by chronic pain.
Economic Inequality, the Working Poor, and Belief in the American Dream
Authors: Newman Benjamin J
Published: December 2022

Does exposure to economic inequality undermine belief in the American dream? Scholarship has long argued that the availability of meritocratic ideologies like the American dream inoculates people against exposure to inequality by leading them to rationalize unequal outcomes by viewing wealth as due to hard work and poverty as due to indolence. The existence of inequality where the “have-nots” are working poor, however, could serve to undermine such a process because their employment status casts them as “deserving poor” and limits the applicability of agency-based explanations for poverty. Across two experiments embedded in national surveys, exposure to inequality alone did not cause significant reductions in belief in the American dream; however, exposure to inequality where the have-nots were working poor significantly reduced belief in the American dream. Moderation and mediation analyses indicate these effects were most pronounced among lower-income Americans and indirectly heightened support for government reduction of inequality.
SKY LTD (FORMERLY SKY PLC) v SKYKICK UK LTD
Authors:   Court of Appeal
Published: December 2022

H1 Trade Marks — European trade marks — SKY — Validity — Broad specifications of goods and services — Bad faith — Requirement of clarity and precision — Lack of bona fide intention to use — Declarations of intention to use — “Computer software” — Partial validity — Case management — “Electronic mail services” — Infringement — Likelihood of confusion — Lack of evidence of confusion — Whether necessary to consider all alleged acts of infringement — Passing off — Application of the judgment on reference to Court of Justice — Appeal to Court of Appeal
Both Diet and Sociality Affect Primate Brain-Size Evolution
Authors: Grabowski Mark , Kopperud Bjørn T , Tsuboi Masahito , Hansen Thomas F
Published: December 2022

Increased brain size in humans and other primates is hypothesized to confer cognitive benefits but brings costs associated with growing and maintaining energetically expensive neural tissue. Previous studies have argued that changes in either diet or levels of sociality led to shifts in brain size, but results were equivocal. Here we test these hypotheses using phylogenetic comparative methods designed to jointly account for and estimate the effects of adaptation and phylogeny. Using the largest current sample of primate brain and body sizes with observation error, complemented by newly compiled diet and sociality data, we show that both diet and sociality have influenced the evolution of brain size. Shifting from simple to more complex levels of sociality resulted in relatively larger brains, while shifting to a more folivorous diet led to relatively smaller brains. While our results support the role of sociality, they modify a range of ecological hypotheses centered on the importance of frugivory, and instead indicate that digestive costs associated with increased folivory may have resulted in relatively smaller brains. [adaptation; allometry; bayou; evolutionary trend; energetic constraints; phylogenetic comparative methods; primate brain size; Slouch; social-brain hypothesis.]
Bone morphogenetic protein 4 is involved in cadmium-associated bone damage
Authors: Wan Yu , Mo Li-jun , Wu Lu , Li Dong-li , Song Jia , Hu You-kun , Huang Hai-bin , Wei Qin-zhi , Wang Da-peng , Qiu Jian-min , Zhang Zi-ji , Liu Qi-zhan , Yang Xing-fen
Published: December 2022

Cadmium (Cd) is a well-characterized bone toxic agent and can induce bone damage via inhibiting osteogenic differentiation. Bone morphogenetic protein (BMP)/SMAD signaling pathway can mediate osteogenic differentiation, but the association between Cd and BMP/SMAD signaling pathway is yet to be illuminated. To understand what elements of BMPs and SMADs are affected by Cd to influence osteogenic differentiation and if BMPs can be the biomarkers of which Cd-induced osteoporosis, human bone marrow mesenchymal stem cells (hBMSCs) were treated with cadmium chloride (CdCl2) in vitro to detect the expression of BMPs and SMADs, and 134 subjects were enrolled to explore if the BMPs can be potential biomarkers of Cd-associated bone damage. Our results showed that Cd exposure significantly promoted the adipogenic differentiation of hBMSCs and inhibited its osteogenic differentiation by inhibiting the expression of BMP-2/4, SMAD4, and p-SMAD1/5/9 complex. And mediation analyses yielded that BMP-4 mediated 39.32% (95% confidence interval 7.47, 85.00) of the total association between the Cd and the risk of Cd-associated bone damage. Moreover, during differentiation, BMP-4 had the potential to enhance mineralization compared with CdCl2 only group. These results reveal that BMP-4 can be a diagnostic biomarker and therapeutic target for Cd-associated bone damage.
Systolic and diastolic left ventricular function in children with primary hypertension: a systematic review and meta-analysis
Authors: Rus Rina R. , Pac Michał , Obrycki Łukasz , Sağsak Elif , Azukaitis Karolis , Sinha Manish D. , Jankauskiene Augustina , Litwin Mieczysław
Published: December 2022

Objective:

Evaluation of left ventricular function provides early evidence of target-organ damage in children with primary hypertension. We performed a systematic review and meta-analysis of left ventricular systolic and diastolic function in children and adolescents with primary hypertension.

Methods:

Literature search was performed in PubMed database and out of 718 articles (published between 2000 and 2021) 22 studies providing comparison of left ventricular function parameters between children with primary hypertension and normotensive controls were selected.

Results:

Overall, 3460 children (5–21 years) with primary hypertension were analyzed. Meta-analysis showed that hypertensive patients when compared with normotensives, had an increased heart rate (mean difference [MD] 5.59; 95% confidence interval [CI] 3.28, 7.89; 10 studies) and increased fractional shortening (MD 1.04; 95% CI 0.48, 1.60; 9 studies) but did not differ in ejection fraction (MD −0.03; 95% CI −1.07, 1.02; 12 studies). Stroke volume was higher in one out of three studies, whereas no differences in cardiac output were found in two studies with available data. Hypertensive children had also lower E/A values (MD −0.21; −0.33, −0.09; 14 studies), greater values of E/e′ (MD 0.59; 0.36, 0.82; 8 studies) and greater global longitudinal stress (MD 2.50; 2.03, 2.96; 4 studies) when compared to those with normotension.

Conclusion:

Our results indicate that hypertensive children and adolescents present with signs of hyperkinetic function of the left ventricle, demonstrate evidence of increased left ventricular strain and impaired diastolic function compared to normotensive controls.
Systolic blood pressure at age 40 and cognitive function 25 years later: the Akershus Cardiac Examination (ACE) 1950 Study
Authors: Walle-Hansen Marte M. , Berge Trygve , Vigen Thea , Myrstad Marius , Hagberg Guri , Ihle-Hansen Hege , Sandset Else C. , Thommessen Bente , Ariansen Inger K.H. , Lyngbakken Magnus N. , Røsjø Helge , Rønning Ole M. , Tveit Arnljot , Ihle-Hansen Håkon
Published: December 2022

Objectives:

Hypertension in midlife is a risk factor for cognitive impairment. Still, the ideal midlife blood pressure (BP) remains unknown. We examined associations between different systolic blood pressure (SBP) levels at the age of 40–43 years and change in SBP over a 25-year period with cognitive function at age 62–65 years.

Methods:

We included 2424 individuals born in 1950 who had participated both in the Age 40 Program (1990–1993) and the Akershus Cardiac Examination (ACE) 1950 Study (2012–2015). The exposure was SBP at age 40–43 years and the outcome was cognitive function at age 62–65 years, assessed with Montreal Cognitive Assessment, Delayed recall trial from the Consortium to Establish a Registry for Alzheimer's Disease Word List Memory Task, and Trail Making Test part B (TMT B).

Results:

Participants were 40.1 ± 0.3 years old with mean SPB 128 ± 13 mmHg at the Age 40 Program, and 63.9 ± 0.6 years old with mean SPB 138 ± 18 at the ACE 1950 Study. Adjusted linear regressions showed no associations between SBP and subsequent cognitive function. In logistic regressions, individuals with SBP ≥140 mmHg, compared to individuals with SBP <120 mmHg (odds ratio 2.29, 95% confidence interval 1.28–4.10, P-value 0.005) had increased risk of an abnormal TMT B-score. Change in SBP during the 25-year follow-up was not associated with cognitive function.

Conclusions:

SBP ≥140 mmHg at age 40–43 was associated with reduced capacity on TMT B, a domain specific cognitive test sensitive to vascular impairment. No other associations were found between SBP, or change in SBP, and cognitive function.
Impact of oscillometric measurement artefacts in ambulatory blood pressure monitoring on estimates of average blood pressure and of its variability: a pilot study
Authors: Bothe Tomas L. , Bilo Grzegorz , Parati Gianfranco , Haberl Ralph , Pilz Niklas , Patzak Andreas
Published: December 2022

Objective:

Ambulatory blood pressure monitoring (ABPM) plays an important role in the diagnosis of hypertension. However, methodological factors and the measurement conditions affect the results and may lead to incorrect classification of the patient. We performed a pilot study to evaluate the impact of oscillometric measurement artefacts on ABPM-derived variables.

Methods:

Four classes of artefacts have been detected: motor activity artefacts, cuff errors, cardiovascular arousals, and arrhythmias. The data consisted of uncorrected measurements (all data), corrected measurements (all artefact free data), and artefact affected data.

Results:

A total of 30 individuals (9 female/21 male), aged between 36 and 86 years, mean: 65.5 (standard deviation: 9.5) were included in the study. The average blood pressure (BP) was higher in artefacts-affected measurements compared the artefact-free measurements both for systolic (4.6 mmHg) and diastolic (1.3 mmHg) measurements. Further, artefact-affected systolic BP (SBP) was 6.4 mmHg higher than artefact-free measurements during daytime. Nocturnal measurements showed no artefact-depended differences. Individual comparisons yielded that 23% of the participants crossed the threshold for BP classification for either 24-h, daytime or nocturnal hypertension when comparing uncorrected and artefact-free measurements. Dipping classification changed within 24% of participants. BP variability was 21 and 12% higher for SPB and DBP, respectively, during daytime. These differences were even higher (27% for SBP and 21% for DPB) during night-time.

Conclusion:

The study reveals that measurement artefacts are frequently present during cuff-based ABPM and do relevantly affect measurement outcome. Exclusion of measurement artefacts is a promising approach to improving cuff-based ABPM accuracy.
Reflections on the Process of Implementing Trauma-Informed Education Lunch and Learns
Authors: Najjar Rana , Jacobs Sarah , Keeney Sarah , Vidal Graciela , Noone Joanne
Published: December 2022

Background:

The trauma-informed education (TIE) framework can help create an equitable learning environment supportive of all learners.

Problem:

Stress and trauma can be impediments to academic success for students, particularly from backgrounds historically excluded from nursing.

Approach:

This article shares the initial steps of a training program on implementing a series of Lunch and Learns (LLs) on TIE in a school of nursing to introduce TIE to faculty and staff and obtain their feedback on facilitators and barriers to implementing recommended approaches.

Outcomes:

The series was well attended, averaging 33 participants per session. Using experts in TIE positively impacted the learning but contributed to inconsistencies in presentation style and scaffolding of content across sessions.

Conclusion:

Purposeful recruitment and engagement of faculty during the development of the LLs were effective in increasing attendance. Multiple sessions require early planning and meetings with team and presenters to ensure consistency and better use of resources.
Persistently Elevated Risk of Syphilis Among Human Immunodeficiency Virus-Positive Men Receiving Care in a Status-Neutral Setting: A Retrospective Analysis
Authors: Shalev Noga , Castor Delivette , Morrison Ellen , Quigee Daniela , Huang Simian , Zucker Jason
Published: December 2022

Background

Over the past decade, the incidence of primary and secondary syphilis has increased dramatically in the United States and Western Europe. Men living with human immunodeficiency virus (HIV) and those at risk of HIV infection experience disproportionately high rates of early syphilis (ES). We compared the odds of ES among HIV-positive and HIV-negative men participating in a status-neutral comprehensive HIV prevention and treatment program (CHP).

Methods

We conducted a retrospective analysis of men aged 18 to 65 years with ≥ 1 CHP visit and ≥2 rapid plasma reagin (RPR) tests performed between January 1, 2018, and December 31, 2021. Early syphilis was defined as newly reactive RPR with a minimum titer of ≥1:4 or a ≥ 4-fold increase in the RPR titer. Multiple logistic regression analyses were performed to determine predictors of ES.

Results

A total of 2490 men met the inclusion criteria, of whom 1426 (57.3%) were HIV-positive and 1064 (42.7%) were HIV-negative. Of the 393 men with ES, 284 (72.3%) were HIV-positive and 109 (27.7%) were HIV-negative. Human immunodeficiency virus-positive men had higher adjusted odds of ES (adjusted odds ratio, 2.86; 95% confidence interval, 2.45–3.27) than HIV-negative men did. Chlamydia or gonorrhea infection did not differ according to HIV status (adjusted odds ratio, 0.93; 95% confidence interval, 0.82–1.04).

Conclusions

In our status-neutral care setting, HIV-positive status was associated with significantly higher odds of ES, but not chlamydia or gonorrhea. Our findings emphasize the vulnerability of HIV-positive men to syphilis in an era of effective HIV biomedical prevention.
INCREASE IN CHLORIDE IS ASSOCIATED WITH MAJOR ADVERSE KIDNEY EVENTS IN CRITICALLY ILL PATIENTS
Authors: Zhou Dingxin , Jiang Jun , Zhang Jing , Cao Fengsheng , Peng Zhiyong
Published: December 2022

Purpose: This study aimed to identify the association between hyperchloremia at intensive care unit (ICU) admission and/or the increase of blood chloride levels and the incidence of major adverse kidney events within 30 days (MAKE30) in critically ill adults. Methods: We conducted a retrospective study to analyze the data of all adult patients admitted to the ICU of a tertiary academic hospital in China between April 2020 and April 2022. Patients were categorized based on their admission chloride levels (hyperchloremia ≥110 mmol/L and nonhyperchloremia <110 mmol/L) and stratified on the increased chloride levels 48 h after ICU admission (∆Cl ≥5 mmol/L and ∆Cl <5 mmol/L). The primary outcome was the MAKE30 incidence, including in-hospital death, new receipt of renal replacement therapy (RRT), and persistent renal dysfunction (PRD). Association between hyperchloremia at ICU admission and/or the increase of chloride and the incidence of MAKE30 were assessed using logistic regression. Result: A total of 2,024 patients with a median age of 67 years (interquartile range [IQR], 55–76 years) and a median Acute Physiology and Chronic Health Evaluation II score of 22 (IQR, 17–28) were included. Hyperchloremia occurred in 30.9% (n = 625), and ΔCl ≥5 mmol/L occurred in 18.5% (n = 375) of all ICU patients. The overall MAKE30 incidence was 33.6% (n = 680), including a 10.9% of 30-day hospital mortality (n = 220; as well as overall in-hospital mortality, 11.8% [n = 238]), a 20.2% (n = 408) of PRD, and a 18.0% (n = 365) of new RRT. After adjusted for confounders, it was found that ΔCl ≥5 mmol/L (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.096–1.93; P = 0.010), but not hyperchloremia (OR, 0.99; 95% CI, 0.77–1.28; P = 0.947), was associated with increased incidence of MAKE30. Conclusion: An increased chloride level in the first 48 h of ICU admission was an independent risk factor for MAKE30, whereas hyperchloremia at ICU admission was not associated with an increased incidence of MAKE30. Large-scale prospective studies are needed to verify our findings.
Single-cell RNA sequencing reveals the distinctive roles of CD4+and CD8+T cells in autoimmune uveitis
Authors: Kang Hao , Sun Hongjian , Yang Yang , Shu Minglei , Wei Yunbo , Zhang Yu , Yu Di , Tao Yong
Published: December 2022

Uveitis is a common cause of blindness and classified as infectious or non-infectious types. Non-infectious uveitis is often secondary to systemic autoimmune diseases, with Behçet’s disease (BD) and Vogt-Koyanagi-Harada disease (VKHD) as the two most common causes. Uveitis in BD and VKHD often show similar clinical manifestations, but the underlying immunopathogenesis remains unclear. We collected immune cell infiltrates in aqueous humour of BD and VKHD uveitis patients and analysed them by single-cell RNA paired with T cell receptor (TCR) sequencing. T cells were found as the dominant immune cell infiltration. Intriguingly, a majority of CD4+in T cell infiltrates was only observed in VKHD but not in BD. In agreement with this discrepancy between VKHD and BD, T cell clonality analysis and Clonotype Neighbour Graph Analysis (CoNGA) also revealed a selective expansion of pro-inflammatory CD4+T cell clones in VKHD. In contrast, BD showed a selective expansion of pro-inflammatory CD8+T cell clones. Our study reveals distinct immunopathogenesis of uveitis driven by CD4+T cells in VKHD and by CD8+T cells in BD, and therefore suggests differential approaches for their diagnosis and therapy.
What do people think of intuitive eating? A qualitative exploration with rural Australians
Authors: Van Dyke Nina , Murphy Michael , Drinkwater Eric J
Published: December 2022

Evidence supports that intuitive eating is associated with many indicators of positive physical and mental health, with more recent longitudinal studies establishing causality. Most research, however, comprises either survey data or clinical trials. This study attempts to fill this evidentiary gap by using a qualitative methodology to explore people’s understandings and reactions to intuitive eating, including perceived barriers and enablers to implementation.

Three focus group discussions were conducted in a non-metropolitan region of Victoria, Australia, with a total of 23 participants. Focus group transcripts were thematically analysed using a grounded theory approach within a constructionist perspective.

Findings indicate that the concept of intuitive eating was either unknown or misunderstood. Once intuitive eating was explained, most responses to implementing intuitive eating were negative. Participants felt that having complete choice around what they ate was unlikely to equate to a healthy or balanced diet, at least in the short term. They also argued that because everyday life was not intuitive in its structures, it would be difficult to eat intuitively. Despite these difficulties, participants appreciated that if they were able to overcome the various barriers and achieve a state of intuitive eating, they anticipated a range of long-term benefits to health and weight management. For intuitive eating to become a viable public health approach, this research suggests that people would need assistance overcoming their existing habits and food preferences, and developing insight into their bodies’ needs, desires, and cravings. The structural barriers, however, would likely continue to be substantial. Most significantly, however, are the barriers imposed by the food environment. Intuitive eating requires choice of foods, yet ample evidence demonstrates that true choice is often not available and that healthful and less healthful foods are not evenly presented.