bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural basis of how the BIRC6/SMAC complex regulates apoptosis and autophagy
Authors: Ehrmann Julian F. , Grabarczyk Daniel B. , Heinke Maria , Deszcz Luiza , Kurzbauer Robert , Hudecz Otto , Shulkina Alexandra , Gogova Rebeca , Meinhart Anton , Versteeg Gijs A. , Clausen Tim
Published: August 2022

Inhibitor of apoptosis proteins (IAPs) bind to pro-apoptotic proteases, keeping them inactive and preventing cell death. BIRC6 is an exceptionally large, multidomain IAP that inhibits its targets by means of its atypical ubiquitin ligase activity and in addition, functions as an inhibitor of autophagy by depleting LC3B. Little is known of the mechanisms by which BIRC6 interacts with its targets and fulfills these two roles. Here, we determined the cryo-EM structure of BIRC6 alone and in complex with two mitochondrial pro-apoptotic proteins, HTRA2 and SMAC. We show BIRC6 is an antiparallel homodimer that forms a crescent shape that arcs around a spacious cavity. The cavity is surrounded by binding sites for client proteins, where they interact with the flexible UBC domain that mediates ubiquitin ligation. Functional data reveal that multivalent binding of SMAC in the central cavity obstructs substrate binding, impeding ubiquitination of both autophagy and apoptotic target proteins. Together our data reveal the molecular mechanisms of how SMAC specifically binds and inhibits BIRC6 to promote apoptosis, and how this regulatory mechanism also extends to autophagy substrates. The interaction sites are hot spots of cancer and atrophy mutations, highlighting the importance of carefully balancing the interplay between BIRC6 and SMAC.
Positional cues underlie cell fate specification during branching morphogenesis of the embryonic mammary epithelium
Authors: Carabaña Claudia , Sun Wenjie , Perkins Meghan , Kapoor Varun , Journot Robin , Hartani Fatima , Faraldo Marisa M. , Lloyd-Lewis Bethan , Fre Silvia
Published: August 2022

How cells coordinate morphogenetic cues and fate specification during development is a fundamental question at the basis of tissue formation. Lineage tracing studies have demonstrated that many stratified epithelia, including the mammary gland, first arise from multipotent stem cells, which are progressively replaced by distinct pools of unipotent progenitors that maintain tissue homeostasis postnatally. The lack of specific markers for early fate specification in the mammary gland has prevented the delineation of the features and spatial localization of lineage-committed progenitors that co-exist with multipotent stem cells (MaSCs) during tissue development. Here, using single-cell RNA-sequencing across 4 stages of embryonic development, we reconstructed the differentiation trajectories of multipotent mammary stem cells towards basal and luminal fate. Our data revealed that MaSCs can already be resolved into distinct populations exhibiting lineage commitment at the time coinciding with the first sprouting events of mammary branching morphogenesis (E15.5). By visualizing gene expression across our developmental atlas, we provide novel molecular markers for committed and multipotent MaSCs, and define their spatial distribution within the developing tissue. Furthermore, we show that the mammary embryonic mesenchyme is composed of two spatially-restricted cell populations, representing the sub-epithelial and dermal mesenchyme. Mechanistically, we explored the communication between different subsets of mesenchymal and epithelial cells, using time-lapse analysis of mammary embryonic explant cultures, and reveal that mesenchymal-produced FGF10 accelerates embryonic mammary branching morphogenesis without affecting cell proliferation. Altogether, our data elucidate the spatiotemporal signals underlying lineage specification of multipotent mammary stem cells and uncover the paracrine interactions between epithelial and mesenchymal cells that guide mammary branching morphogenesis.
Treatment history shapes the evolution of complex carbapenem-resistant phenotypes in Klebsiella spp.
Authors: Rosas Natalia C. , Wilksch Jonathan J. , Barber Jake , Li Jiahui , Wang Yanan , Sun Zhewei , Rocker Andrea , Webb Chaille , Perlaza-Jiménez Laura , Stubenrauch Christopher , Vijaykrishna Dhanasekaran , Song Jiangning , Taiaroa George , Davies Mark , Strugnell Richard A. , Bao Qiyu , Zhou Tieli , McDonald Michael J. , Lithgow Trevor
Published: August 2022

Antibiotic resistance is driven by selection, but how a bacterial strain’s evolutionary history shapes drug-resistance remains an open question. Here we reconstruct the genetic and evolutionary mechanisms of carbapenem resistance in a clinical isolate of Klebsiella. A combination of short and long read sequencing, machine learning, genetic and enzymatic analyses established that this carbapenem-resistant strain carries no carbapenemase-encoding genes. Genetic reconstruction of the resistance phenotype confirmed that two distinct genetic loci are necessary for the strain to acquire carbapenem resistance. Experimental evolution of the carbapenem-resistant strains in growth conditions without the antibiotic revealed that both loci confer a significant cost, and are readily lost by de novo mutation resulting in the rapid evolution of a carbapenem-sensitive phenotype. Thus, historical contingency - a patient’s treatment history - can shape the evolution of antibiotic resistance and suggests that the strategic combinations of antibiotics could direct the evolution of low-fitness, drug-resistant genotypes.
Impact on S. aureus and E. coli membranes of treatment with chlorhexidine and alcohol solutions: insights from molecular simulations and nuclear magnetic resonance
Authors: Waller Callum , Marzinek Jan , McBurnie Eilish , Bond Peter J , Williamson Philip T. F. , Khalid Syma
Published: August 2022

Membranes form the first line of defence of bacteria against potentially harmful molecules in the surrounding environment. Understanding the protective properties of these membranes represents an important step towards development of targeted anti-bacterial agents such as sanitizers. Use of propanol, isopropanol and chlorhexidine can significantly decrease the threat imposed by bacteria in the face of growing anti-bacterial resistance via mechanisms that include membrane disruption. Here we have employed molecular dynamics simulations and nuclear magnetic resonance to explore the impact of chlorhexidine and alcohol on the S. aureus cell membrane, as well as the E. coli inner and outer membranes. We identify how sanitizer components partition into these bacterial membranes, and show that chlorhexidine is instrumental in this process.
Crystal structure of a novel homodimericD-allulose 3-epimerase from a Clostridia bacterium
Authors: Xie Xiaofang , Tian Yixiong , Ban Xiaofeng , Li Caiming , Yang Hongshun , Li Zhaofeng
Published: August 2022

D-Allulose, a low-calorie rare sugar with various physiological functions, is mainly produced through the isomerization of D-fructose by ketose 3-epimerases (KEases), which exhibit various substrate specificities. A novel KEase from a Clostridia bacterium (CDAE) was identified to be a D-allulose 3-epimerase and was further characterized as thermostable and metal-dependent. In order to explore its structure–function relationship, the crystal structure of CDAE was determined using X-ray diffraction at 2.10 Å resolution, revealing a homodimeric D-allulose 3-epimerase structure with extensive interactions formed at the dimeric interface that contribute to structure stability. Structural analysis identified the structural features of CDAE, which displays a common (β/α)8-TIM barrel and an ordered Mn2+-binding architecture at the active center, which may explain the positive effects of Mn2+on the activity and stability of CDAE. Furthermore, comparison of CDAE and other KEase structures revealed several structural differences, highlighting the remarkable differences in enzyme–substrate binding at the O4, O5 and O6 sites of the bound substrate, which are mainly induced by distinct hydrophobic pockets in the active center. The shape and hydrophobicity of this pocket appear to produce the differences in specificity and affinity for substrates among KEase family enzymes. Exploration of the crystal structure of CDAE provides a better understanding of its structure–function relationship, which might provide a basis for molecular modification of CDAE and further provides a reference for other KEases.
Numerical study of the effect of winglet on the aerodynamic performance of sinusoidal and simple leading-edge wings
Authors: Naderinezhad Mahdi , Djavareshkian M.H.
Published: August 2022

Purpose

This study aims to investigate the effectiveness of two types of winglets, multi-tip and raked, on the performance of sinusoidal and simple leading-edge wings and compares it by a numerical method.

Design/methodology/approach

The wing configuration in this study is rectangular and uses NACA0020 section, and all simulations are performed by a numerical method based on finite volume and base pressure algorithm in Reynolds 2 × [10]^5. In the mentioned numerical method, the flow is considered turbulent, and the k-ω-SST model is used. To calculate the stresses on the wing surface, the mesh is extended to below the viscous layer, and a second-order upstream accuracy is used to calculate the convection flux.

Findings

The use of raked and multi-tip winglets for the sinusoidal edge of the wing improved aerodynamic performance by 5.12 and 2.28%, respectively, and the greatest effect of these two winglets was on increasing the lifting force and reducing the inductive drag, respectively. Also, by examining the distribution of induced vortices around the configurations, it was found that the curvature of the sinusoidal wing tip at the angles of attack before stall reduced the strength of the induced vortices and, the use of winglet during and after stall, caused increased aerodynamic performance of the sinusoidal wing.

Practical implications

The whale is an international species of aquatic animal found in most of the world’s oceans. It has large fin aspect ratios that have a series of bulges at the edge of the attack, which improves the aerodynamic performance near and after stall. Today, one of the fields of research is the use of this idea in the wings of micro air vehicle.

Originality/value

Winglet reduces induced drag in simple wings. So far, the effect of winglets on wings with sinusoidal attack edges has not been investigated.
The practical challenges faced by young entrepreneurs: an empirical analysis
Authors: Khursheed Ambreen , Mustafa Faisal , Fatima Maham , Rao Marriam
Published: August 2022

Purpose

This study proposes a new comprehensive model of entrepreneurial intentions (EIs) that enhances the understanding of the crucial entrepreneurial personality traits. This study also examines how entrepreneurial family history, gender and discipline moderate the relationship between the key entrepreneurial personality traits and EIs of university students.

Design/methodology/approach

The study introduces a new combination of important entrepreneurial personality traits, theoretically following the theory of planned behaviour (TPB). The data are collected using an entrepreneurial intention questionnaire and analysed with structural equation modelling (SEM) over a sample of 297 university students from Pakistan.

Findings

The findings highlight that one of the notable contributions to assessing EI is the negative impact of foreseeable challenges (FCs), resulting in negative EIs among university students of our sample. The authors also found significant moderating roles of gender, discipline and entrepreneurial family history in strengthening the relationship between entrepreneurial traits and EIs.

Originality/value

The study contributes both to the existing empirical and theoretical literature by examining a key set of entrepreneurial personality traits leading to enhance EIs. The results may also assist academicians to discover new ways for developing entrepreneurial traits among university students.
Risk governance, ethics codes and bank performance: evidence from large banks worldwide
Authors: Kacem Oumeima , El Harbi Sana
Published: August 2022

Purpose

This paper has a triple objective: first, to investigate the effect of the adoption of ethics codes on bank performance, second, to analyse the role played by the risk committee (RC) effectiveness in improving bank performance and finally, to assess the indirect role that the implementation of ethics codes exerts on the latter relationship.

Design/methodology/approach

The research questions are examined using an international sample of large banks worldwide from 2006 to 2017, applying the dynamic generalized method of moments (GMM) model for panel data.

Findings

The authors find that risk management committee size and independence have a positive and significant effect on bank performance. This highlights the importance of the risk governance function in enhancing bank performance. Most importantly results reveal that although larger RC tends to improve bank performance, this linkage is less strong when adopting ethical codes. They also find that the adoption of ethical codes by banks positively affects the relationship between the functioning of RC and performance.

Originality/value

Although it is well known that risk management, business ethics and performance are interrelated, there is no research that has dealt with this question.
A systematic literature review and bibliometric analysis of noise trading
Authors: Gupta Sanjay , Walia Nidhi , Singh Simarjeet , Gupta Swati
Published: August 2022

Purpose

This comprehensive study aims to take a punctilious approach intended to present qualitative and quantitative knowledge on the emerging concept of noise trading and identify the emerging themes associated with noise trading.

Design/methodology/approach

This study combines bibliometric and content analysis to review 350 publications from top-ranked journals published from 1986 to 2020.

Findings

The bibliometric and content analysis identified three major themes: the impact of noise traders on the functioning of the stock market, traits of noise traders and different proxies used to measure the impact of noise trading.

Research limitations/implications

This study undertakes research papers related to the field of finance, published in peer-reviewed journals and that too in the English language.

Practical implications

This study shall accommodate rational traders, portfolio consultants and other investors to gain deeper insights into the functioning of noise traders. This will further help them to formulate their trading/investment strategies accordingly.

Originality/value

The successful combination of the bibliometric and content analysis revealed major gaps in the literature and provided future research directions.
Development of trilayered multifunctional superhydrophobic cotton fabric using biogenic materials
Authors: Gayathri A. , Varalakshmi P. , Sethuraman M. G.
Published: August 2022

Purpose

This study aims to develop multifunctional, namely, superhydrophobic, flame-retardant and antibacterial, coatings over cotton fabric, using casein as green-based flame-retardant and silver nanoparticles as antibacterial agent by solution immersion method.

Design/methodology/approach

The cotton fabric is first coated with casein to make it flame-retardant. AgNPs synthesized using Cinnamomum zeylanicum bark extract is coated over the casein layer. Finally, stearic acid is used to coat the cotton to make it superhydrophobic. X-ray diffraction, transmission electron microscopy analysis and ultraviolet-visible spectroscopy are used to investigate the produced AgNPs. The as-prepared multifunctional cotton is characterized by scanning electron microscopy, energy dispersive X-ray analysis and attenuated total reflection-infrared studies. Flame test, limiting oxygen index test and thermogravimetric analyzer studies have also been performed to study the flame-retardant ability and thermal stability of treated fabric, respectively. The antibacterial effect of the coatings is evaluated by disc-diffusion technique. Water contact angle is determined to confirm the superhydrophobic nature of cotton fabric.

Findings

The outcomes of this study showed that the prepared multifunctional cotton fabric had maximum contact angle of greater than 150° with good flame retardancy, high thermal stability, greater washing durability and high antibacterial activity against the growth of Pseudomonas aeruginosa and Acinetobacter indicus. Additionally, the as-prepared superhydrophobic cotton showed an excellent oil–water separation efficiency.

Research limitations/implications

The trilayered multifunctional cotton fabric has limiting washing durability up to 20 washing cycles. Treated functional fabric can be used as an antibacterial, therapeutic, water repellent and experimental protective clothing for medical, health care, home curtains and industrial and laboratory purposes.

Originality/value

The study brings out the robustness of this method in the development of multifunctional cotton fabrics.
Experiences of face mask use during the COVID‐19 pandemic: A qualitative study
Authors: Hanna Esmée , Martin Graham , Campbell Anne , Connolly Paris , Fearon Kriss , Markham Steven
Published: August 2022

The use of face masks and coverings has been a central component of efforts to mitigate the impact of the COVID‐19 pandemic and has been legally mandated in some countries. Most academic studies to date, however, have focussed primarily on its effectiveness in reducing SARS‐CoV‐2 transmission, largely neglecting the social dimensions of mask mandates. In this narrative interview‐based study, we consider experiences of face masks, with a particular focus on groups considered to be at a potential disadvantage from compulsory masking. Drawing on 40 telephone, video‐call and e‐mail interviews, we highlight the impact of inconsistent communication and the notion of mask wearing as an act of altruism on participants’ experiences. In particular, we show how intolerance towards individuals who did not wear masks could result in stigma and exclusion, regardless of the legitimacy of their reasons. We suggest that more is needed to mitigate the ‘dark side’ of discourses of collective effort and altruism at a time of societal stress and fracture, and to account for the needs and interests of groups for whom compulsory masking may result in further marginalisation.
The legitimation of school-based Bildung in the context of vocational education and training: The legacy of Eduard Spranger
Authors: Gonon Philipp
Published: August 2022

The philosophical foundation of Bildung in the context of vocational education and training was significantly shaped by Eduard Spranger (1882–1963). However its legacy is not as present today since vocational schools in german-speaking countries today focus strongly on competences. This article sheds light on the emergence of this concept, discusses the impact up to the present and reconstructs the debates surrounding it.
Xiaoketongbi Formula vs pregabalin for painful diabetic neuropathy: A single‐center, randomized, single‐blind, double‐dummy, and parallel controlled clinical trial
Authors: Lu Qiyun , Chen Benjian , Liang Qingshun , Wu Liyan , Luo Lulu , Li Anxiang , Ouyang Wenwei , Wen Zehuai , Liu Yunwei , Lu Jiayan , Liu Yunyi , Fan Guanjie , Liu Zhenjie
Published: August 2022

Background

We assessed the efficacy and safety of the Xiaoketongbi Formula (XF) vs. pregabalin in patients with painful diabetic neuropathy (PDN).

Methods

Patients with PDN (n = 68) were included in a single‐center, randomized, single‐blind, double‐dummy, parallel controlled clinical trial. The primary outcome was the change in the Brief Pain Inventory for Diabetic Peripheral Neuropathy (BPI‐DPN). Secondary outcomes evaluated included the reduction of BPI‐DPN >50%, changes in the numeric rating scale‐11 (NRS‐11) score for pain, Daily Sleep Interference Diary (DSID), Patient Global Impression of Change (PGIC), nerve conduction velocity (NCV), and adverse events.

Results

After 10 weeks of treatment, the BPI‐DPN score reduced from 42.44 ± 17.56 to 26.47 ± 22.22 and from 52.03 ± 14.30 to 37.85 ± 17.23 in the XF and pregabalin group (Ps < 0.001), respectively. The difference in the absolute change in BPI‐DPN score between both groups was −1.79 (95% CI: −9.09, 5.50; p = 0.625). In the XF and pregabalin groups, 44.1% (15/34) and 20.6% (7/34) of patients reported a BPI‐DPN reduction >50% (p = 0.038), respectively. There were no significant differences between groups in NRS‐11 and DSID (Ps > 0.05). A significantly greater number of patients in the XF group felt “significantly improved” or “improved” than in the pregabalin group (35.3% (12/34) vs. 11.8% (4/34), p = 0.045). The absolute change in motor nerve conduction velocity of the right median nerve was significantly different between both groups (XF group 0.7 ± 2.3 vs. pregabalin group −2.2 ± 4.1, p = 0.004). No serious adverse events were reported in either group.

Conclusions

XF is equivalent to pregabalin in reducing pain symptoms and improves the quality of life in patients with PDN. In addition, XF has the potential to improve nerve function by increasing NCV.
A fast, precise, in‐vivo method for micron‐level 3D models of corals using dental scanners
Authors: Quigley Kate M.
Published: August 2022

Several sampling and measurement strategies have been developed to assess biological forms in three dimensions, including corals. However, the effectiveness (in speed and precision) of current three‐dimensional (3D) methods in scanning and model construction are challenging at small scales (μm–mm).

In this paper, a practical 3D scanning and model construction tool using an intra‐oral dental scanner was assessed to measure the surface area and volume of coral juveniles across multiple species. Intra‐oral scanners using confocal imaging are fast, precise to the μm scale and safe to use with live tissue, thereby eliminating the need to harm or kill the animals. The trial was conducted at the National Sea Simulator at the Australian Institute of Marine Science.

High‐quality 3D scans of individual coral juveniles were successfully generated and integrated automatically into high‐resolution (μm) mesh from point clouds. The attained average scanning efficiency was <2 min/individual, without a significant difference in speed given coral complexity or between live colonies or dead coral skeletons.

Overall, this fast and precise system could become a promising tool for marine environmental surveys and restoration initiatives. This tool also removes the need to sacrifice animals for measurement analysis, thereby increasing conservation and animal welfare.
The echo of the world: The castaway, the Garabandal apparitions, and the crisis of presence
Authors: Martínez‐Hernáez Ángel
Published: August 2022

In the early 1990s, while I was conducting an ethnographic study in a psychosocial rehabilitation center in Barcelona for people suffering from psychosis, a patient and informant gave me four letters that he had supposedly sent to various recipients. Only recently did I discover that these letters, which warned of terrible catastrophes, were related to the Marian apparitions of Garabandal in the 1960s in Spain, and that their recipients had all been involved in this amazing event. This discovery led me to attempt an ethnographic reparation, and to reconsider the letters as a way of inhabiting the world. With this objective and drawing on Ernesto de Martino's concept of “crisis of presence,” I propose to understand the informant's experience as an extreme example of the porosity of presence. I conclude that the letters can be understood as the affected person's struggle for being in a human history. [crisis of presence, Garabandal apparitions, reflexivity, schizophrenia]
Dynorphin promotes stress‐induced depressive behaviors by inhibiting ventral pallidal neurons in rats
Authors: Ji Miao‐Jin , Gao Zhi‐Qiang , Yang Jiao , Cai Ji‐Heng , Li Ke‐Xue , Wang Jie , Zhang Hongxing , Zhou Cheng‐Hua , Cao Jun‐Li , Liu Chao
Published: August 2022

Aim

Endogenous dynorphin signaling via kappa opioid receptors (KORs) plays a key role in producing the depressive and aversive consequences of stress. We investigated the behavioral effects of the dynorphin/KOR system in the ventral pallidum (VP) and studied the underlying mechanisms.

Methods

To investigate the effects of dynorphin on the VP, we conducted behavioral experiments after microinjection of drugs or shRNA and brain‐slice electrophysiological recordings. Histological tracing and molecular biological experiments were used to identify the distribution of KORs and the possible sources of dynorphin projections to the VP.

Results

An elevated dynorphin concentration and increased KOR activity were observed in the VP after acute stress. Infusion of dynorphin‐A into the VP produced depressive‐like phenotypes including anhedonia and despair and anxiety behaviors, but did not alter locomotor behavior. Mechanistically, dynorphin had an inhibitory effect on VP neurons—reducing their firing rate and inhibiting excitatory transmission—through direct activation of KORs and modulation of downstream G‐protein‐gated inwardly rectifying potassium (GIRK) channels and high‐voltage gated calcium channels (VGCCs). Tracing revealed direct innervation of VP neurons by dynorphin‐positive projections; potential sources of these dynorphinergic projections include the nucleus accumbens, amygdala, and hypothalamus. Blockade of dynorphin/KOR signaling in the VP by drugs or viral knock‐down of KORs significantly reduced despair behavior in rats.

Conclusions

Endogenous dynorphinergic modulation of the VP plays a critical role in mediating depressive reactions to stress.
Antibody and T‐cell responses by ultra‐deep T‐cell receptor immunosequencing after COVID‐19 vaccination in patients with plasma cell dyscrasias
Authors: Chung Alfred , Banbury Barbara , Vignali Marissa , Huang Chiung‐Yu , Asoori Sireesha , Johnson Rachel , Kurtz Theodore , Arora Shagun , Wong Sandy W. , Shah Nina , Martin Thomas G. , Wolf Jeffrey L.
Published: August 2022

We investigated antibody and coronavirus disease 2019 (COVID‐19)‐specific T‐cell mediated responses via ultra‐deep immunosequencing of the T‐cell receptor (TCR) repertoire in patients with plasma cell dyscrasias (PCD). We identified 364 patients with PCD who underwent spike antibody testing using commercially available spike‐receptor binding domain immunoglobulin G antibodies ≥2 weeks after completion of the initial two doses of mRNA vaccines or one dose of JNJ‐78436735. A total of 56 patients underwent TCR immunosequencing after vaccination. Overall, 86% tested within 6 months of vaccination had detectable spike antibodies. Increasing age, use of anti‐CD38 or anti‐B‐cell maturation antigen therapy, and receipt of BNT162b2 (vs. mRNA‐1273) were associated with lower antibody titres. We observed an increased proportion of TCRs associated with surface glycoprotein regions of the COVID‐19 genome after vaccination, consistent with spike‐specific T‐cell responses. The median spike‐specific T‐cell breadth was 3.11 × 10−5, comparable to those in healthy populations after vaccination. Although spike‐specific T‐cell breadth correlated with antibody titres, patients without antibody responses also demonstrated spike‐specific T‐cell responses. Patients receiving mRNA‐1273 had higher median spike‐specific T‐cell breadth than those receiving BNT162b2 (p = 0.01). Although patients with PCD are often immunocompromised due to underlying disease and treatments, COVID‐19 vaccination can still elicit humoral and T‐cell responses and remain an important intervention in this patient population.
Incident heart failure, arrhythmias and cardiovascular outcomes with sodium‐glucose cotransporter 2 (SGLT2) inhibitor use in patients with diabetes: Insights from a global federated electronic medical record database
Authors: Fawzy Ameenathul Mazaya , Rivera‐Caravaca José Miguel , Underhill Paula , Fauchier Laurent , Lip Gregory Y. H.
Published: August 2022

Aim

To investigate the impact of sodium‐glucose cotransporter 2 (SGLT2) inhibitors on the risk of incident heart failure and adverse cardiovascular outcomes.

Methods

All patients with diabetes who were registered between January 2018 and December 2019 were identified from a federated electronic medical record database (TriNetX) and followed up for 2 years. A 1:1 propensity‐score matching (PSM) analysis was performed to balance the SGLT2 inhibitor and non‐SGLT2 inhibitor cohorts. The primary outcome was incident heart failure. Secondary outcomes included all‐cause mortality, cardiac arrest, ventricular tachycardia/ventricular fibrillation (VT/VF), incident atrial fibrillation (AF), ischaemic stroke/transient ischaemic attack (TIA), composite of arterial and venous thrombotic events, and composite of incident VT/VF and cardiac arrest.

Results

A total of 131 189 and 2 692 985 patients were treated with and without SGLT2 inhibitors, respectively. After PSM, 131 188 patients remained in each group. The risk of incident heart failure was significantly lower in the SGLT2 inhibitor cohort compared to the non‐SGLT2 inhibitor cohort (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.68‐0.73). SGLT2 inhibitor use was also associated with a significantly lower risk of all‐cause mortality (HR 0.61, 95% CI 0.58‐0.64), cardiac arrest (HR 0.70, 95% CI 0.63‐0.78), incident AF (HR 0.81, 95% CI 0.76‐0.84), ischaemic stroke/TIA (HR 0.90, 95% CI 0.88‐0.93), composite of arterial and venous thrombotic events (HR 0.90, 95% CI 0.88‐0.92), and composite of incident VT/VF and cardiac arrest (HR 0.76, 95% CI 0.71‐0.81). There were no significant differences for VT/VF (HR 0.94, 95% CI 0.88‐1.00).

Conclusion

Use of SGLT2 inhibitors was associated with a significant reduction in the risk of incident heart failure and adverse cardiovascular outcomes but not ventricular arrhythmias.
Q&A with Justen Lewis
Authors: Lewis Justen
Published: August 2022

A design enthusiast shares his recent experience at DMI's Diversity in Design conference and the importance of diversity, equity, and inclusion in his future.
The Role of Design Managers in Implementing Sustainability
Authors: Delaney Emelia , Liu Wei
Published: August 2022

The need and demand for socially and environmentally responsible products from consumers has also increased, with customers demanding more sustainable products through their purchasing behavior and product feedback.

Consumers are expressing a greater desire for sustainability in the products they buy and services they use. Design managers just may hold the key to making sustainability a reality.
Predictors of heart failure and all‐cause mortality in asymptomatic patients with moderate and severe aortic regurgitation
Authors: Lavine Steven J , Raby Kirsten
Published: August 2022

Background

Class I indications for aortic valve replacement (AVR) for severe chronic aortic regurgitation (AR) include AR attributable symptoms or left ventricular (LV) ejection fraction <50%. As noninvasive estimates of elevated LV filling pressures (LVFP's) have been noted to predict heart failure (HF) readmission and all‐cause mortality (ACM) in HF patients, we hypothesize that elevated LVFP's may also be independent predictors of HF and ACM in chronic AR.

Methods

We developed a single center patient database of moderate or greater AR diagnoses between 2003 and 2008 and followed each patient through January 2013. We included patients with >30 days follow‐up with interpretable Doppler‐echocardiograms. We recorded demographic variables, EuroScore II, incident HF and ACM, and Doppler‐echo variables of LV size, systolic and diastolic function.

Results

Patients with severe AR (105 patients) and moderate AR (201 patients) had similar EuroScore II values and similar incident HF and ACM. For the 180 patients who developed HF, effective arterial elastance (aHR = 1.70 (1.01–2.83), p = .041), LV end‐diastolic dimension (aHR = 1.83, (1.11–3.03), p = .0176), E/e’ (aHR = 3.04, (1.83–5.05), p < .0001), eccentric hypertrophy (EH) (aHR = 2.39, (1.62–5.12), p = .0004), and tricuspid regurgitation (TR) velocity (aHR = 5.75, (3.70–10.36), p < .0001) were independent predictors. For the 118 patients with ACM, EH (aHR = 1.73, (1.02–3.28), p = .0414), systolic blood pressure (aHR = .58, (.33–.95), p = .0301), left atrial volume index (aHR = 1.82, (1.06–3.06), p = .0293), E/e’ (aHR = 1.83, (1.07–3.08), p = .0280), and TR velocity (aHR = 4.14, (2.22–6.49), p < .0001) were independent predictors.

Conclusions

Elevated TR velocity and EH were strong markers of HF and ACM in patients with asymptomatic severe AR and in moderate AR.
A protocol for reproducible functional diversity analyses
Authors: Palacio Facundo X. , Callaghan Corey T. , Cardoso Pedro , Hudgins Emma J. , Jarzyna Marta A. , Ottaviani Gianluigi , Riva Federico , Graco‐Roza Caio , Shirey Vaughn , Mammola Stefano
Published: August 2022

The widespread use of species traits in basic and applied ecology, conservation and biogeography has led to an exponential increase in functional diversity analyses, with > 10 000 papers published in 2010–2020, and > 1800 papers only in 2021. This interest is reflected in the development of a multitude of theoretical and methodological frameworks for calculating functional diversity, making it challenging to navigate the myriads of options and to report detailed accounts of trait‐based analyses. Therefore, the discipline of trait‐based ecology would benefit from the existence of a general guideline for standard reporting and good practices for analyses. We devise an eight‐step protocol to guide researchers in conducting and reporting functional diversity analyses, with the overarching goal of increasing reproducibility, transparency and comparability across studies. The protocol is based on: 1) identification of a research question; 2) a sampling scheme and a study design; 3–4) assemblage of data matrices; 5) data exploration and preprocessing; 6) functional diversity computation; 7) model fitting, evaluation and interpretation; and 8) data, metadata and code provision. Throughout the protocol, we provide information on how to best select research questions, study designs, trait data, compute functional diversity, interpret results and discuss ways to ensure reproducibility in reporting results. To facilitate the implementation of this template, we further develop an interactive web‐based application (stepFD) in the form of a checklist workflow, detailing all the steps of the protocol and allowing the user to produce a final ‘reproducibility report' to upload alongside the published paper. A thorough and transparent reporting of functional diversity analyses ensures that ecologists can incorporate others' findings into meta‐analyses, the shared data can be integrated into larger databases for consensus analyses, and available code can be reused by other researchers. All these elements are key to pushing forward this vibrant and fast‐growing field of research.
Role of kappa‐opioid and mu‐opioid receptors in pruritus: Peripheral and central itch circuits
Authors: Kim Brian S. , Inan Saadet , Ständer Sonja , Sciascia Thomas , Szepietowski Jacek C. , Yosipovitch Gil
Published: August 2022

Modern genetic approaches in animal models have unveiled novel itch‐specific neural pathways, emboldening a paradigm in which drugs can be developed to selectively and potently target itch in a variety of chronic pruritic conditions. In recent years, kappa‐opioid receptors (KORs) and mu‐opioid receptors (MORs) have been implicated in both the suppression and promotion of itch, respectively, by acting on both the peripheral and central nervous systems. The precise mechanisms by which agents that modulate these pathways alleviate itch remains an active area of investigation. Notwithstanding this, a number of agents have demonstrated efficacy in clinical trials that influence both KOR and MOR signalling. Herein, we summarize a number of opioid receptor modulators in development and their promising efficacy across a number of chronic pruritic conditions, such as atopic dermatitis, uremic pruritus and beyond.
Neuro‐weighted multi‐functional nearest‐neighbour classification
Authors: Yue Guanli , Qu Yanpeng , Deng Ansheng , Zhang Qianyi
Published: August 2022

Background

The performance of nearest‐neighbour classification is highly sensitive to the quality of data. In order to reduce the impact of the inevitable existence of irrelevant features in data, this paper employs the information learned by neural networks to implement a feature weighting technique and associated weighted multi‐functional nearest‐neighbour classification method.

Method

The non‐iterative neural networks are easy to implement while enjoying remarkable computational efficiency. In this paper, four non‐iterative neural networks (ELM, E‐ELM, RAWN and RVFL) are employed to evaluate the significance of features to decisions learned and stored in the parameters of neural networks. Moreover, the bias of the significance of features is comforted by using cross‐validation. The resulting feature significance is converted into feature weights to further implement weighted multi‐functional nearest‐neighbour classification.

Result

The experimental results demonstrate that the proposed neuro‐weighted feature weighting strategy can effectively reduce the impact of irrelevant features and enhance the performance of multi‐functional nearest‐neighbour classification.

Contribution

The proposed algorithm explores an avenue to efficiently utilize the learned knowledge of neural networks to reduce the role of irrelevant feature in nearest‐neighbour classification.
Computing the durability of WAAM 18Ni 250 maraging steel specimens
Authors: Peng Daren , Jones Rhys , Ang Andrew S. M. , Michelson Alex , Champagne Victor , Birt Aaron , Pinches Samuel , Kundu Sudip , Alankar Alankar , Singh Raman R. K.
Published: August 2022

MIL‐STD 1530D requires that the certification of an aircraft part employ analytical tools that are capable of modeling crack growth. It is further stated that the durability and damage tolerance (DADT) analyses should be based on linear elastic fracture mechanics (LEFM) and follow a building block approach. This paper illustrates the durability analysis required to certify an additively manufactured part by using the examples of durability tests performed on two wire arc additively manufactured (WAAM) 18Ni 250 Maraging steel specimens.
Efficient regulated entry in competitive markets with demand uncertainty
Authors: Bajo‐Buenestado Raúl
Published: August 2022

It is well‐known that, in a competitive market, the number of firms in a free‐entry equilibrium is the efficient one. This paper shows that this textbook result breaks down if firms face demand uncertainty. In this case, entry is excessive relative to the optimum and, therefore, regulation improves market efficiency. This occurs because, in the absence of regulation, entry is motivated by the profits that firms expect to receive if market demand turns out to be high. However, when choosing the optimal regulated entry, the planner also considers that some surplus is lost if demand turns out to be low.
The change of clinical features and surgical outcomes in patients with pressure injury during the COVID‐19 pandemic
Authors: Huang Ching‐Ya , Chang Chiung‐Wen , Lee Sheng‐Lian , Chen Chiehfeng , Chen Jin‐Hua , Wang Hsian‐Jenn , Chiu Wen‐Kuan
Published: August 2022

This retrospective study aims to explore whether the COVID‐19 pandemic altered patient conditions and surgery outcomes by studying 213 pressure injury (PI) patients who underwent surgery during 2016 to 2019 (pre‐COVID) and 2020 to 2021 (COVID) in Taiwan. We extracted patient demographics, surgical and blood test records, preoperative vital signs, and flap surgery outcomes. In total, 464 surgeries were performed, including 308 pre‐COVID and 156 COVID. During the COVID period, there were more patients presenting with dementia, and it had significantly more patients with >12 000 white blood cells/μL (24.03% vs 15.59%, P = 0.029), higher C‐reactive protein levels (7.13 ± 6.36 vs 5.58 ± 5.09 mg/dL, P = 0.014), pulse rates (86.67 ± 14.76 vs 81.26 ± 13.66 beats/min, P < 0.001), and respiratory rates (17.87 ± 1.98 vs 17.31 ± 2.39 breaths/min, P = 0.009) but lower haemoglobin levels (9.75 ± 2.02 vs 10.43 ± 1.67 mg/dL, P < 0.001) preoperatively. There were no between‐group differences in flap surgery outcomes but had fewer flap surgeries during COVID‐19. Thus, PI patient condition was generally poor during the COVID‐19 pandemic because of reduced access to medical treatment; this problem may be resolved through holistic care during a future pandemic or pandemic‐like situation.
Effect of groups size on students' learning achievement, motivation, cognitive load, collaborative problem‐solving quality, and in‐class interaction in an introductory AI course
Authors: Zhan Zehui , He Guoqing , Li Tingting , He Luyao , Xiang Siyu
Published: August 2022

Background

Group size is one of the important factors that affect collaborative learning, however, there is no consensus in the literature on how many students should the groups be composed of during the problem‐solving process.

Objectives

This study investigated the effect of group size in a K‐12 introductory Artificial Intelligence course by comparing the students' cognitive load, learning motivation, collaborative problem‐solving quality, and in‐classroom interaction between two‐ and three‐student groups.

Methods

Forty‐eight high school students were randomly assigned to two kinds of groups (i.e., the two‐student group, and the three‐student group, each consisting of 24 students). During the experiment, Xiaofei robots were used to teach the theoretical and practical content of five AI topics over 6 weeks for 1.5 h each week.

Results

The ANOVA results indicated that group size mattered in the AI course, the two‐student group was more effective in terms of enhancing students' learning motivation and collaborative problem‐solving quality, as well as imposing more cognitive load than the three‐student group. The advantage was more obvious in the practical problem context. The Lag Sequential Analysis results indicated that more collaborative learning behavioural sequences existed in the two‐student group than in the three‐student groups.

Contribution

This research provides empirical evidence and potential guidance for group design in Artificial Intelligence Education. Although group size did not affect students' learning achievement, it affected learning motivation, cognitive load, and problem‐solving quality and processes. Two‐student groups work better than three‐student groups in the AI course.
Extracellular vesicles produced by bone marrow mesenchymal stem cells overexpressing programmed death‐ligand 1 ameliorate dextran sodium sulfate‐induced ulcerative colitis in rats by regulating Th17/Treg cell balance through PTEN/PI3K/AKT/mTOR axis
Authors: He Hongxia , Chen Qianyun , Fan Heng , Leng Xue yuan , Zhu Feng , Gao Fei , Zhou Qiaoli , Dong Yalan , Yang Jia
Published: August 2022

Background and Aim

Programmed death‐ligand 1 (PD‐L1) was involved in regulating Th17/Treg cell balance in ulcerative colitis (UC). Extracellular vesicles (EVs) from genetically modified bone marrow mesenchymal stem cells (BMSCs) can serve as a stable delivery system to overexpress PD‐L1. The study was designed to evaluate the therapeutic mechanism of BMSC‐EVs overexpressing PD‐L1 (PD‐L1‐EVs) on ulcerative colitis.

Methods

Experimental model of UC was established in rats by drinking 5% dextran sulfate sodium (DSS). Apoptosis‐related proteins, inflammatory response‐related factors and oxidative stress related mediators were detected. Westernblot was used to detecte key proteins in the PI3K/AKT signaling pathway and its downstream effectors. The CD4+Foxp3+Treg cells and CD4+IL‐17A+Th17 cells in spleen and mesenteric lymph nodes (MLNs) was detected by flow cytometry.

Results

PD‐L1‐EVs significantly alleviated the manifestations and pathological damage of UC rats by inhibiting the expression of IFN‐γ, IL‐1β, IL‐8, IL‐6, IL‐2, BAX, NF‐κB, TNF‐α, MPO, and MDA, and up‐regulating the expression of IL‐4, BCL‐2, SOD, and GSH. Furthermore, the proportions of Th17 cells were decreased and that of Treg cells were upregulated by PD‐L1‐EVs treatment. PTEN inhibitors (bpv) partially abolished the inhibitory effect of PD‐L1‐EVs on PI3K‐AKT signaling and impaired the therapeutic efficacy of PD‐L1‐EVs.

Conclusions

PD‐L1‐EVs mitigated colonal inflammation, apoptosis and oxidative stress through blocking the activation of PI3K/Akt/mTOR pathway and regulating the balance of Th17/Treg cells.
Morphometry of cryopreserved organs from the gastrointestinal system of squirrel monkeys (Saimiri sciureus, Linnaeus, 1758) for improvement of management
Authors: Andrade Márcia Cristina Ribeiro , Lemos Bárbara Regina Pickler , de Araújo Lopes Cláudia Andréa , de Jesus Barbosa Ribeiro Margarida , da Silva Larissa Melo , Knackfuss Fabiana Batalha , Viana Clênio Fernandes
Published: August 2022

Background

Nonhuman primates (NHPs) are fundamental for countless types of research and their phylogenetic similarities with humans make them valuable biomodels.Saimiri(squirrel monkeys) is the New World simian genus that is most widely used in research; however, little is known about the morphology of the gastrointestinal tract (GIT) of these animals.

Methods

The morphological and topographical aspects of GIT organs from 14 previously frozen carcasses of captive squirrel monkeys (Saimiri sciureus) were described as a means for refining clinical and laboratory diagnoses, with the aim of providing a basis for clinical assessments and animal management. The carcasses were gradually thawed, macroscopically evaluated for their appearance, measured, weighed, photographed, and necropsied. The characteristics of all the GIT organs (main and accessories) were evaluated, with measurement of the dimensions and description of the shape, consistency, and color of each one.

Results

The stomach of squirrel monkeys is simple and of non‐compartmentalized type and the cecum does not have numerous folds, compared with other species. These characteristics are compatible with omnivorous simian species with no adaptive digestive specialization for the food fermentation process. Significant correlations were found between the weights of the carcass and GIT (p < .05); carcass and tongue (0.83;p < .01); and liver and right salivary gland (0.83;p < .01). It was also observed that the animals showed good body score conformation and GIT organs in good condition, which indicated that their nutritional management had been adequate. Regarding the correlations found among the organs: (i) squirrel monkeys with heavier carcasses had better‐developed GIT with greater food storage capacity; (ii) the bigger the animal was, the greater its overall muscle development was, including that of the tongue, which would enable intensification of its feeding activity; and (iii) the measurements of the esophagus, small and large intestines, pancreas, and salivary glands were not sex‐dependent inSaimiri sciureus.

Conclusions

Previously cryopreserved carcasses of squirrel monkeys can be used for gastrointestinal system studies, with the potential to make clinical, zootechnical, management, and scientific contributions.