bluuebunny/crossref_metadata_2025 huggingface dataset:
Intracellular BAPTA directly inhibits PFKFB3, thereby impeding mTORC1-driven Mcl-1 translation and killing Mcl-1-addicted cancer cells
Authors: Sneyers Flore , Kerkhofs Martijn , Welkenhuyzen Kirsten , Speelman-Rooms Femke , Shemy Ahmed , Voet Arnout , Eelen Guy , Dewerchin Mieke , Tait Stephen W. , Ghesquière Bart , Bootman Martin D. , Bultynck Geert
Published: November 2022

Intracellular Ca2+signals control several physiological and pathophysiological processes. The main tool to chelate intracellular Ca2+is intracellular BAPTA (BAPTAi), usually introduced into cells as a membrane-permeant acetoxymethyl ester (BAPTA-AM). We previously demonstrated that BAPTAienhanced apoptosis induced by venetoclax, a Bcl-2 antagonist, in diffuse large B-cell lymphoma (DLBCL). These findings implied a novel interplay between intracellular Ca2+signaling and anti-apoptotic Bcl-2 function. Hence, we set out to identify the underlying mechanisms by which BAPTAienhances cell death in B-cell cancers. In this study, we observed that BAPTAialone induced apoptosis in lymphoma cell models that were highly sensitive to S63845, an Mcl-1 antagonist. BAPTAiprovoked a rapid decline in Mcl-1 protein levels by inhibiting mTORC1-drivenMCL-1translation. Overexpression of nondegradable Mcl-1 rescued BAPTAi-induced cell death. We further examined how BAPTAidiminished mTORC1 activity and found that BAPTAiimpaired glycolysis by directly inhibiting 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) activity, an up to now unkown effect of BAPTAi. All aforementioned effects of BAPTAiwere also elicited by a BAPTAianalog with low affinity for Ca2+. Thus, our work reveals PFKFB3 inhibition as an unappreciated Ca2+-independent mechanism by which BAPTAiimpairs cellular metabolism and ultimately the survival of Mcl-1-dependent cancer cells. Our work has two important implications. First, direct inhibition of PFKFB3 emerged as a key regulator of mTORC1 activity and a promising target in the treatment of Mcl-1-dependent cancers. Second, cellular effects caused by BAPTAiare not necessarily related to Ca2+signaling. Our data support the need for a reassessment of the role of Ca2+in cellular processes when findings were based on the use of BAPTAi.
Emergent remote stress-focusing drive submucosal collagen fiber remodeling in intestinal anastomotic surgery
Authors: Fleischer Brian P. , Nguyen Nhung , Pal Anshuman , Kim Julius , Khabaz Kameel , Tsamis Alkiviadis , Efrati Efi , Witten Thomas , Alverdy John C. , Pocivavsek Luka
Published: November 2022

Following resection of a diseased segment of intestine, a reconnection (anastomotic) geometry is chosen to reduce postoperative stress and optimize outcomes. As proper healing of an intestinal anastomosis is strongly affected by its mechanobiology, much attention has been devoted to the conical structures formed along the suture lines, where stress-focusing is expected. However, geometric considerations reveal that in addition to the obvious loci of stress-focusing, additional remote locations of stress-focusing may form. We identify conical structures that inevitably form within regions of otherwise uninterrupted tissue. In this work we use geometric analysis, finite element modeling (FEM), and in-vivo experiments to investigate these emergent stress-focusing structures, their mechanical stresses, and the resulting submucosal collagen fiber re-orientation, as these naturally arise in the side-to-side small bowel anastomosis (SBA), the most common configuration performed in patients. FEM predicts the appearance of remote high-stress regions. Allowing for tissue remodeling, our simulations also predict an increased dispersion of submucosal collagen fibers in these regions. In-vivo experiments performed on ten-week-old male C57BL/6 mice assigned the creation of side-to-side SBA or sham-laparotomy corroborate this result. Anastomoses were analyzed at sacrifice on post-operative day (POD) 14 and 88 with histologic-sectioning, staining, high magnification imaging, and submucosal collagen fiber orientation (κ) mapping. The mean and variance ofκ, a measure of collagen fiber dispersion, at POD-14 far from the anastomosis show similar values to those obtained for sham-operated mice, while the FEM-predicted loci of stress-focusing display statistically significant higher values. The values at POD-88 at all loci show no statistically-significant difference, and agree with those of the sham-operated mice at POD-14.
IL-6 suppresses vaccine responses in neonatal mice by enhancing IL-2 activity on T follicular helper cells
Authors: Parvathaneni Swetha , Yang Jiyeon , Lotspeich-Cole Leda , Sakai Jiro , Lee Robert C , Akkoyunlu Mustafa
Published: November 2022

The inability of neonates to develop CD4+CXCR5+PD−1+T follicular helper (TFH) cells contributes to their weak vaccine responses. In adult mice, IL-6 promotes TFH-cell expansion by suppressing the expression of IL-2Rβ on TFHcells. Here, we found a totally opposite role for IL-6 in neonatal mice TFHresponse. Whereas co-injection of neonatal mice with IL-6 and a conjugate polysaccharide vaccine suppressed TFHresponse by increasing the production of IL-2 and expression of IL-2Rα and IL-2Rβ on TFHcells, immunization of IL-6 knock-out neonatal mice led to improved antibody responses accompanied by expanded TFHcells as well as lower levels of IL-2 and IL-2 receptors on TFHcells. Moreover, CpG containing vaccine improved TFHresponse in neonates while suppressing the expression of IL-2 receptors on TFHcells, suggesting that CpG protects TFHcells by inhibiting IL-2 activity. These findings unveil age specific differences in IL-6 mediated vaccine responses and highlight the need to consider age related immunobiological attributes in designing vaccines.
Classification of harmonic homomorphisms between Riemannian three-dimensional unimodular Lie groups
Authors: Abdelkader Zagane , Nada Osamnia , Zegga Kaddour
Published: November 2022

Purpose

The purpose of this study is to classify harmonic homomorphisms ϕ : (G, g) → (H, h), where G, H are connected and simply connected three-dimensional unimodular Lie groups and g, h are left-invariant Riemannian metrics.

Design/methodology/approach

This study aims the classification up to conjugation by automorphism of Lie groups of harmonic homomorphism, between twodifferent non-abelian connected and simply connected three-dimensional unimodular Lie groups (G, g) and (H, h), where g and h are two left-invariant Riemannian metrics on G and H, respectively.

Findings

This study managed to classify some homomorphisms between two different non-abelian connected and simply connected three-dimensional uni-modular Lie groups.

Originality/value

The theory of harmonic maps into Lie groups has been extensively studied related homomorphism in compact Lie groups by many mathematicians, harmonic maps into Lie group and harmonics inner automorphisms of compact connected semi-simple Lie groups and intensively study harmonic and biharmonic homomorphisms between Riemannian Lie groups equipped with a left-invariant Riemannian metric.
Corporate disclosures and financial distress in banks in India: the moderating role of competition
Authors: Rastogi Shailesh , Kanoujiya Jagjeevan
Published: November 2022

Purpose

This study aims to determine the association of Transparency and Disclosure (TD) with financial distress (FID) while the competition (as Lerner Index) moderates the association between the two.

Design/methodology/approach

The panel data analysis (static model) is performed to examine the effect of disclosures on the bank's FID. A TD index is built to assess the level of TD. All three versions of Altman's Zscore are employed to measure a bank's FID (High Zscore is opposite of FID). The data of 34 banks running in India for the timeframe 2015–16 to 2018–19 is utilized. Lerner index (LI) is taken as the moderator. The bank-size, valuation and financial leverage are control variables.

Findings

There exists no linear connection between TD and FID. However, TD is positively associated with financial stability (opposite FID). It means TD initially reduces financial stability and improves it after TD crosses a threshold level. Competition (as LI, where the higher value of LI means reduced competition) negatively moderates the association of TD with financial stability. Hence, the findings of this study support the competition-fragility premise. Surprisingly, the negatively significant interaction term of LI and TD implies either high competition and high TD or low competition with low TD, which helps in the bank's financial stability.

Originality/value

The findings provide input to a long-term policy of disclosures and competition in the banking sector, keeping in view the financial stability of the banks. Therefore, findings are novel and carry immense value to the existing knowledge on the topic.
Learning of quality improvement theory – experiences with reflective learning from a student perspective
Authors: Hellberg Roland , Fauskanger Eivind
Published: November 2022

Purpose

The purpose of this study is to investigate how professionals who are continuing their education rate a higher education quality management course with an emphasis on reflective learning and real problem-solving. The audited course consists of module-based teaching, while students work on an improvement project at their workplace between course sessions. This study has a twofold aim: to contribute to the design of quality improvement courses based on doing as we learn and to offer insight into the use of a final grading method that consist of a folder with reports from the intermediate work steps and a final report.

Design/methodology/approach

After completing the course, students received a survey with questions and statements about the course content, delivery and final grading methods. They answered these questions on a seven-point Likert scale and also answered open-ended questions.

Findings

It is clear that professional students value the interweaving of theory with real-life training, and they value module-based teaching in which theory is reviewed and applied to practical problems. Reflective learning was achieved through feedback from both teachers and fellow students on various interim reports. Students’ employers benefit from the course, as students gain experience with quality improvement. The grading of a final report on the improvement project based on three sub-assignments was highly appreciated.

Practical implications

Developers in courses in quality improvement benefit from learning how this course is structured, assessed and how participants perceived its components.

Originality/value

The course design with modules and intermediate work steps, where the students apply theory in quality improvement to a real project at their workplace, is an original concept. The modules correspond to the plan, do, check and act (PDCA) methodology.
Determinants of mental disorders of Afghan migrants during the COVID-19 pandemic
Authors: Khozaei Fatemeh , Carbon Claus-Christian , Abd Razak Nordin
Published: November 2022

Purpose

Afghan migrants are at an increased risk of mental disorders due to various political, economic and security-associated stressors. COVID-19 has brought extra concerns for this group of migrants around the world. Few studies have examined how the perception of the host society and perceived stress are associated with the mental health of migrants during the COVD-19 pandemic. This study aims to examine the role of perceived justice, freedom and the burden of COVID-19 on experienced stress and depression among Afghan migrants in Iran.

Design/methodology/approach

N = 497 participants representing the Afghan migrant community between 15 and 80 years old participated in the study. The target population was recruited from Afghan migrants residing in Kerman city in Iran, the capital of one of the provinces with the highest number of Afghan migrants in Iran. The participants answered questions on depression, positive mental health and a series of stressors such as perceived justice, freedom and the burden of COVID-19. Data was collected in November and December 2021 during the third wave of the COVID-19 pandemic in Iran.

Findings

The authors found a significant effect of the burden of the COVID-19 pandemic on migrants’ perceived stress and depression. On the other hand, perceptions of justice and freedom in the host country can significantly reduce stress and depression. The results show that stress mediates the effect of justice, freedom and the burden of COVID-19 on depression. In addition, positive mental health moderates the impact of stress on depression.

Originality/value

The current study is one of the pioneering studies that examines the determinants of Afghan migrants’ mental disorders during the COVID-19 pandemic in Iran.
Data analytics dynamic capabilities for Triple-A supply chains
Authors: Daneshvar Kakhki Mohammad , Rea Alan , Deiranlou Mehdi
Published: November 2022

Purpose

This study aims to analyze the mediating role of data analytics management capability (DAMC) in the relationship between supply chain integration (SCI) and supply chain agility, adaptability and alignment (Triple-A). It also studies the role of Triple-A supply chains in performance improvement. We develop and present a model based on our proposition and informed by the dynamic capabilities perspective.

Design/methodology/approach

The authors employ meta-analytic structural equation modeling to test the proposed model by analyzing reported statistics of 117 published studies.

Findings

This study’s results describe why some prior research findings are contradictory. For example, researchers have posited mixed findings on the impact of SCI on agility. The results show that SCI and agility do not have a significant direct association, and DAMC mediates their indirect relationship.

Originality/value

The impact of SCI on performance is debatable. SCI permits access to shared resources for competitive advantage; conversely, SCI-induced rigidity may reduce supply chain agility and adaptability. Informed by dynamic capabilities theory, the authors demonstrate that DAMC positively mediates the impact of SCI on performance.
Do trust and country governance affect credit growth in GCC countries?
Authors: Albaity Mohamed , Saadaoui Mallek Ray , Al-Tamimi Hussein A. Hassan , Molyneux Philip
Published: November 2022

Purpose

This study aims to investigate whether quality of governance (QoG), trustworthiness and confidence impacted bank credit growth in Gulf Cooperation Council (GCC). In addition, it examined whether credit growth differed between Islamic and conventional banks in GCC countries.

Design/methodology/approach

Using data from 104 (56 conventional banks and 48 Islamic banks) banks located in GCC countries from 2012 to 2019, the two-step system generalized method of moments estimator was used to analyse the data.

Findings

Evidence was found of the influence of trust in institutions in boosting credit growth. The QoG generally expanded credit growth which instilled confidence in the economy and the banking sector. Credit growth was more pronounced for Islamic banks. This paper has contributed to the literature evaluating the determinants of credit growth in GCC.

Originality/value

This paper has been one of the few studies exploring the effect of trustworthiness and confidence (informal institutions) and macro governance (formal institutions) in GCC. GCC is different from other regions, as it is oil-dependent and shares similar legal, social and cultural aspects. This suggested that these might yield different results than expected.
Together through tough times: a qualitative study of community resilience to protect against mental health issues in the UK
Authors: Southby Kris , Bidey Tim , Grimes Duncan , Khor Zoe , South Jane , Bagnall Anne-Marie
Published: November 2022

Purpose

Living in an area experiencing economic and social disadvantage is a known risk factor to poor mental health and well-being. This paper aims to understand how some communities experiencing disadvantage appear to be more resilient to the enduring challenges they face and display better mental health outcomes.

Design/methodology/approach

A qualitative case study approach was used. Semi-structured interviews (total = 74) were undertaken remotely with residents (n = 39) and voluntary, community and social enterprise groups, community leaders and other local stakeholders (n = 35) in four case study areas. Data analysis was cross-case, thematic analysis. Community analysis workshops (n = 4) and resilience mapping workshops (n = 4) in each site corroborated emerging insights.

Findings

Four overlapping and interacting themes support community resilience: community hubs and local voluntary, community and social enterprise (VCSE) networks; opportunities to participate and make connections within communities; open and supportive environments to talk about mental health and well-being; and community identities and collective narratives. Differences in access to these resources was a cross-cutting theme.

Originality/value

Community resilience can be understood in terms of the amount of resources – articulated in terms of capital – that communities can draw on in response to challenges, and how well these resources are mobilised. A thriving VCSE sector is important for community resilience in communities experiencing disadvantage as a mechanism for both sustainably building and mobilising community resources in the face of daily and enduring challenges.
Resilience in later life: the impact of social exclusion on access to networks of support
Authors: Bagnall Kirsty , Yarker Sophie
Published: November 2022

Purpose

The aim of this paper is to respond to a gap in the literature around resilience in later life for older people from minority groups of identity or experience. Specifically, it argues that we need to pay greater attention to how access to different types of social capital may leave some older people more or less able to cope with adverse events and how experiences of social exclusion can limit access to important networks of support during times of crisis.

Design/methodology/approach

This paper draws on research conducted to inform the resilience strategy of Greater Manchester in 2019, and specifically looked at how this strategy could better address the needs of the regions’ diverse ageing population. It used a qualitative design including focus groups with older women of Punjabi heritage living in Greater Manchester, interviews with staff from a community and voluntary organisation working with these women, and interviews with staff at an organisation supporting refugees and asylum seekers in Greater Manchester who specifically worked with older adults.

Findings

The research found that belonging to a minority group and experiences of social exclusion gave participants in this study both resources and vulnerabilities when it came to dealing with external shocks in later life. Whilst participants in this study had access to strong networks of bonding capital based on shared identity and experience, social exclusion often meant they faced barriers to accessing network of support outside of these communities.

Research limitations/implications

Findings from this study have implications for both future research and policy. In the case of the latter there are implications for those working in resilience planning in terms of how to address the needs of diverse older populations. For researchers, this paper has implications for how we understand the impacts on inequality in later life particularly in the context of the COVID-19 pandemic.

Originality/value

The originality of this paper lies in its consideration of the impact of inequalities and social exclusion on the resilience of older people in times of crisis. It included older people from minority groups of identity and experience addressing an important gap in the literature.
The benefits of independent older people’s representation and why its development should be supported
Authors: Milsom Steven George
Published: November 2022

Purpose

The purpose of this papers is to set out the advantages to local communities of independent representation of older people by older people through active and vibrant older people’s forums and groups and the rationale for Councils in Wales to support their revitalisation and development.

Design/methodology/approach

This paper describes how semi-structured action research and follow-up discussion and analysis over a two-year period was undertaken by older people with representatives of Older Peoples Forums and groups to identify a strategy to restart and revitalise independent forums post pandemic to represent the voice of older people to government at all levels.

Findings

Facilitation of the independent and self-determined voice of older people through genuine co-production with Forums can help Councils meet statutory duties and ensure their policies and services for older people are developed and informed from the direct experience of those receiving them. This will also help address the impacts of an ageing population and meet the national aim to create age-friendly communities across Wales.

Social implications

This research provides a basis for Councils to work with Independent Older Peoples Forums and groups to restart and regenerate the forums and promote the self-determined voice of older people to government at all levels.

Originality/value

In an ageing society older people should be empowered and enabled to make their own decisions. The principle of self-determination by older people for older people directly and through co-productive engagement with them by local authorities has meaning and purpose that should be promoted and implemented. If age-friendly communities are to be developed across Wales, then collaboration on this basis is required including through independent 50+ forums in localities.
Parent perspectives on student IEP involvement
Authors: Sanderson Kelli A. , Rojas Amanda J.
Published: November 2022

As key members of the Individualised Education Program (IEP) team and strong child advocates, parents play a critical role in special education. In this study, we sought to understand a crucial, yet underexamined, aspect of special education – parent perceptions regarding student participation in IEP development. Specifically, we asked parents how schools could better support student involvement in the IEP process, including IEP meetings. Participants included 646 parents of students with disabilities aged 5–21 years currently receiving special education services across the United States. Constant comparative analysis was used to code data. Qualitative coding revealed four major themes, including: (1) promoting an active student role, (2) supportive school staff, (3) making changes to IEP meetings and (4) considerations and concerns regarding student participation. Implications for practice and policy are discussed.
Intelligent sampling of high‐dimensional joint mobility space for analysis of articular function
Authors: Bishop Peter J. , Brocklehurst Robert J. , Pierce Stephanie E.
Published: November 2022

Studies of joint structure and function have played a central role in understanding palaeobiology and major functional transitions in evolutionary history, where fossilized hard parts (e.g. bones) are often all that remain. Current digital methods for quantifying articular function depend on exhaustively sampling all possible joint poses, but this is computationally intensive, becoming prohibitively so with more degrees of freedom. This has impeded more sophisticated analyses or broader application of these methods to more diverse questions and species.

The present study introduces ‘APSE’ (Accelerated Pose Searching with Electrostatics), an iterative algorithm for rapidly and intelligently sampling high‐dimensional joint pose space to quantify articular function and mobility. Key features of the algorithm are: known viable joint poses inform the search for new poses in successive generations; the search preferentially targets under‐explored regions of pose space, while avoiding over‐explored regions; large swaths of inviable pose space are never evaluated, thus minimizing wasted time; and parallelizability. The efficacy of the algorithm was benchmarked with diverse theoretical and biological joints. As a case study to demonstrate its utility, APSE was used to investigate mobility in the enigmatic shoulder joint of the extinct ‘pelycosaur’‐grade synapsid Dimetrodon, the function of which has been widely debated.

APSE produces high‐dimensional joint mobility assessments with greater precision than state‐of‐the‐art exhaustive sampling methods. More viable poses are identified at a greater sampling density, but in a fraction of the time taken by current methods (hours, not days or weeks). Results for Dimetrodon shoulder mobility indicate strong coupling between most degrees of freedom across the joint's full range of motion, a stark contrast to the flexible shoulder of most extant tetrapods.

APSE provides a time‐efficient means to quantitatively measure articular function and mobility, especially when more degrees of freedom are considered. By greatly reducing computational requirements, APSE lowers the barrier to researchers seeking to undertake more complex or more numerous analyses of articular function in modern and extinct animals. This will accelerate the pace of research in comparative or evolutionary analyses of joint and animal function.
All‐cause and liver‐related mortality risk factors in excessive drinkers: Analysis of data from the UK biobank
Authors: Whitfield John B. , Seth Devanshi , Morgan Timothy R. ,   GenomALC Consortium
Published: November 2022

Background

High alcohol intake is associated with increased mortality. We aimed to identify factors affecting mortality in people drinking extreme amounts of alcohol.

Methods

We obtained information from the UK Biobank on approximately 500,000 participants aged 40–70 years at baseline assessment in 2006–2010. Habitual alcohol intake, lifestyle and physiological data, laboratory test results, and hospital diagnoses and death certificate data (to June 2020) for 5136 men (2.20% of male participants) and 1504 women (0.60%) who reported consuming ≥80 or ≥50 g/day, respectively, were used in survival analysis.

Results

Mortality hazard ratios for these excessive drinkers, compared to all other participants, were 2.02 (95% CI 1.89–2.17) for all causes, 1.89 (1.69–2.12) for any cancer, 1.87 (1.61–2.17) for any circulatory disease, and 9.40 (7.00–12.64) for any liver disease. Liver disease diagnosis or abnormal liver function tests predicted not only deaths attributed to liver disease but also those from cancers or circulatory diseases. Mortality among excessive drinkers was also associated with quantitative alcohol intake; diagnosed alcohol dependence, harmful use, or withdrawal syndrome; and current smoking at assessment.

Conclusions

People with chronic excessive alcohol intake experience decreased average survival, but there is substantial variation in their mortality, with liver abnormality and alcohol dependence or other alcohol use disorders associated with a worse prognosis. Clinically, patients with these risk factors and high alcohol intake should be considered for early or intensive management. Research can usefully focus on the factors predisposing to dependence or liver abnormality.
TCR CDR3‐antigen chemical complementarity associated with poor ovarian cancer outcomes: A vestigial immune response to early cancer antigens?
Authors: Barker Vayda R. , Varkhedi Mallika , Patel Dhruv N. , Hsiang Monica , Chobrutskiy Andrea , Chobrutskiy Boris I. , Blanck George
Published: November 2022

Ovarian cancer continues to present significant challenges for early detection and treatment, indicating a need for novel approaches to improve disease outcomes. In this report, we applied a previously described algorithm for detecting chemical complementarity between candidate cancer antigens and complementarity determining region‐3 (CDR3) amino acid sequences from tumor resident T‐cell receptors. Current literature indicates an association between high CDR3‐cancer antigen complementarity and improved survival outcomes. For example, high CDR3‐BRAF electrostatic complementarity is associated with a better melanoma outcome. However, such CDR3‐cancer antigen chemical complementarity in ovarian cancer was largely associated with worse outcomes. Specifically, high CDR3‐MAGEB4 and CDR3‐TDRD1 electrostatic complementarity was associated with lower ovarian cancer disease free survival (DFS). Additionally, high CDR3‐MAGEB4 and CDR3‐TDRD1 electrostatic complementarity was associated with decreased MAGEB4/TDRD1 gene expression and gene copy numbers, consistent with a selection against ovarian cancer cells expressing these antigens. However, when TDRD1 was split into fragments, high CDR3‐TDRD1 hydrophobicity complementarity, for a specific TDRD1 fragment, was associated with increased DFS and higher immune marker expression levels. This dichotomy highlights the myriad of opportunities to establish risk stratifications and to identify potential, actionable cancer antigens using immunogenomic parameters.
Designing novel activities before instruction: Use of contrasting cases and a rich dataset
Authors: Bego Campbell R. , Chastain Raymond J. , DeCaro Marci S.
Published: November 2022

Background

In exploratory learning, students first explore a new topic with an activity and then receive instruction. This inversion of the traditional tell‐then‐practice order typically benefits conceptual knowledge and transfer, but not always.

Aims

The current work examines the impact of including contrasting cases in an exploration activity, which can enhance student perception of novel problem features.

Samples

Undergraduate physics students (Experiment 1, N = 129; Experiment 2, N = 92) participated as part of their regular classroom instruction.

Methods

Students completed an activity either before or after instruction (explore‐first or instruct‐first conditions). In Experiment 1, the activity included contrasting cases; in Experiment 2, the activity instead included a rich dataset. Students completed a post‐test assessing procedural knowledge, conceptual knowledge and transfer.

Results

In Experiment 1, students in the explore‐first condition demonstrated similar procedural knowledge, higher conceptual knowledge and higher transfer than students in the instruct‐first condition. In Experiment 2, there were no significant differences in learning outcomes between explore‐first and instruct‐first conditions. In both experiments, students in the explore‐first and instruct‐first conditions reported similar cognitive load and interest and enjoyment after the activity.

Conclusions

Contrasting cases may be important when designing exploratory learning activities, helping to improve both conceptual understanding and transfer to new topics.
Left visual field bias during face perception aligns with individual differences in reading skills and is absent in dyslexia
Authors: Åsberg Johnels Jakob , Galazka Martyna A. , Sundqvist Maria , Hadjikhani Nouchine
Published: November 2022

Background

When looking at faces, we tend to attend more to the left visual field (corresponding to the right side of the person's face). This phenomenon is called the left visual field bias (LVF) and is presumed to reflect the brain's right‐sided dominance for face processing. Whether alterations in hemispheric dominance are present in dyslexia, and are linked with individual differences in word reading development more generally, is still unclear, and no prior research has utilized gaze‐based LVF bias to explore these topics.

Aims

The aim of the study was to examine whether the LVF bias differs in dyslexia and to examine the association with word‐reading skills assessed dimensionally.

Sample

Forty‐six 9–13 year‐old children with dyslexia and community control children, matched on age and listening comprehension.

Methods

Participants were presented with a recorded face on a screen while their gaze patterns were collected with an eye tracker. Fixations to the left versus the right side of the face stimuli were compared.

Results

Results showed a clear LVF bias in community controls, while no such bias was seen in the dyslexic group. Moreover, the strength of the LVF bias was correlated with better word reading in the controls.

Conclusions

Our results suggest a link between weakened hemispheric dominance for face processing in dyslexia and in poor word reading, at least to the extent that the LVF bias actually mirrors underlying physiology. We discuss the implications of these novel findings, highlighting the need for future research to determine the specificity and developmental sources of LVF bias alterations.
Changes in children’s anger, sadness, and persistence across blocked goals: Implications for self‐regulation
Authors: Tan Lin , Shin Eunkyung , Page Kenyon , Smith Cynthia L.
Published: November 2022

The current study took a person‐centered approach to examine the heterogeneity of changes in children’s emotions and persistence during a goal‐blocking task and examined how different profiles of emotions and persistence related to children’s self‐regulation. Children’s anger, sadness, and persistence were rated in a goal‐blocking task in toddlerhood (T1;N = 140, 72 boys,Mage = 2.67 years, 90.7% White) and preschool (T2). Children’s self‐regulation, specifically sustained attention and engagement, was assessed at T1, T2, and early school‐age (T3) from 2005 to 2012. Growth mixture modeling revealed two classes of children at T1 and three classes at T2 with different patterns of anger, sadness, and persistence. Children’s classification at T2, but not T1, significantly predicted their sustained attention and engagement both concurrently and longitudinally.
The temporal dynamics of Large‐Scale brain network changes in disorders of consciousness: A Microstate‐Based study
Authors: Zhang Chunyun , Yang Yi , Han Shuai , Xu Long , Chen Xueling , Geng Xiaoli , Bie Li , He Jianghong
Published: November 2022

Background and Objectives

The resting‐state brain is composed of several discrete networks, which remain stable for 10–100 ms. These functional microstates are considered the building blocks of spontaneous consciousness. Electroencephalography (EEG) microstate analysis may provide insight into the altered brain dynamics underlying consciousness recovery in patients with disorders of consciousness (DOC). We aimed to analyze microstates in the resting‐state EEG source space in patients with DOC, the relationship between state‐specific features and consciousness levels, and the corresponding patterns of microstates and functional networks.

Methods

We obtained resting‐state EEG data from 84 patients with DOC (27 in a minimally conscious state [MCS] and 57 in a vegetative state [VS] or with unresponsive wakefulness syndrome). We conducted a microstate analysis of the resting‐state (EEG) source space and developed a state‐transition analysis protocol for patients with DOC.

Results

We identified seven microstates with distinct spatial distributions of cortical activation. Multivariate pattern analyses revealed that different functional connectivity patterns were associated with source‐level microstates. There were significant differences in the microstate properties, including spatial activation patterns, temporal dynamics, state shifts, and connectivity construction, between the MCS and VS groups.

Discussion

Our findings suggest that consciousness depends on complex dynamics within the brain and may originate from the anterior cortex.
Immunological mechanisms and treatable traits of chronic rhinosinusitis in Asia: A narrative review
Authors: Yao Yin , Zhu Hong‐Yu , Zeng Ming , Liu Zheng
Published: November 2022

Objectives

To review the current literature on immunological mechanisms and treatable traits of chronic rhinosinusitis (CRS) in Asia.

Design

This is a narrative review of published data on the immunological mechanisms and treatable traits of CRS in Asia. Published English literature on CRS in Asian and Western countries was reviewed. Where available, the data extracted included epidemiology, immunology, bacterium, phenotype, endotype and treatment.

Results and Conclusion

CRS is a heterogeneous disease characterised by persistent locoregional mucosal inflammation of the paranasal sinuses. The inflammatory signatures of CRS vary across patients with distinct racial and ethnic backgrounds and geographic areas. Compared to CRS patients in Western countries, Asian CRS patients display less eosinophilic and Type 2 inflammation, which is associated with lower asthma and allergic rhinitis comorbidities. In contrast, Asian patients with CRS have more prominent non‐eosinophilic inflammation than those in Western countries. In addition, Asian CRS patients may have different bacterial colonisation than patients in Western countries. Our review suggests that the distinct immunological mechanisms between Asian and Western CRS patients may influence the clinical phenotype, responses to treatment and outcomes. The treatable trait is a new strategy and therapeutic target identified by phenotype or endotype and has been proposed as a new paradigm for the management of diseases. Improved understanding of CRS phenotypic and endotypic heterogeneity and incorporation of treatable traits into clinical care pathways may facilitate more effective selections of therapeutic interventions, including surgery and biologics.
Effective conservation planning of Iberian amphibians based on a regionalization of climate‐driven range shifts
Authors: Alagador Diogo
Published: November 2022

Amphibians are severely affected by climate change, particularly in regions where droughts prevail and water availability is scarce. The extirpation of amphibians triggers cascading effects that disrupt the trophic structure of food webs and ecosystems. Dedicated assessments of the spatial adaptive potential of amphibian species under climate change are, therefore, essential to provide guidelines for their effective conservation. I used predictions about the location of suitable climates for 27 amphibian species in the Iberian Peninsula from a baseline period to 2080 to typify shifting species’ ranges. The time at which these range types are expected to be functionally important for the adaptation of a species was used to identify full or partial refugia; areas most likely to be the home of populations moving into new climatically suitable grounds; areas most likely to receive populations after climate adaptive dispersal; and climatically unsuitable areas near suitable areas. I implemented an area prioritization protocol for each species to obtain a cohesive set of areas that would provide maximum adaptability and where management interventions should be prioritized. A connectivity assessment pinpointed where facilitative strategies would be most effective. Each of the 27 species had distinct spatial requirements but, common to all species, a bottleneck effect was predicted by 2050 because source areas for subsequent dispersal were small in extent. Three species emerged as difficult to maintain up to 2080. The Iberian northwest was predicted to capture adaptive range for most species. My study offers analytical guidelines for managers and decision makers to undertake systematic assessments on where and when to intervene to maximize the persistence of amphibian species and the functionality of the ecosystems that depend on them.
Childhood disability: The importance of context
Authors: Rosenbaum Peter
Published: November 2022

Video Podcast: https://youtu.be/BGYdbflAKRE
De novo KCNA6 variants with attenuated KV1.6 channel deactivation in patients with epilepsy
Authors: Salpietro Vincenzo , Galassi Deforie Valentina , Efthymiou Stephanie , O'Connor Emer , Marcé‐Grau Anna , Maroofian Reza , Striano Pasquale , Zara Federico , Morrow Michelle M. ,   SYNAPS Study Group, Reich Adi , Blevins Amy , Sala‐Coromina Júlia , Accogli Andrea , Fortuna Sara , Alesandrini Marie , Au P. Y. Billie , Singhal Nilika Shah , Cogne Benjamin , Isidor Bertrand , Hanna Michael G. , Macaya Alfons , Kullmann Dimitri M. , Houlden Henry , Männikkö Roope
Published: November 2022

Objective

Mutations in the genes encoding neuronal ion channels are a common cause of Mendelian neurological diseases. We sought to identify novel de novo sequence variants in cases with early infantile epileptic phenotypes and neurodevelopmental anomalies.

Methods

Following clinical diagnosis, we performed whole exome sequencing of the index cases and their parents. Identified channel variants were expressed in Xenopus oocytes and their functional properties assessed using two‐electrode voltage clamp.

Results

We identified novel de novo variants in KCNA6 in four unrelated individuals variably affected with neurodevelopmental disorders and seizures with onset in the first year of life. Three of the four identified mutations affect the pore‐lining S6 α‐helix of KV1.6. A prominent finding of functional characterization in Xenopus oocytes was that the channel variants showed only minor effects on channel activation but slowed channel closure and shifted the voltage dependence of deactivation in a hyperpolarizing direction. Channels with a mutation affecting the S6 helix display dominant effects on channel deactivation when co‐expressed with wild‐type KV1.6 or KV1.1 subunits.

Significance

This is the first report of de novo nonsynonymous variants in KCNA6 associated with neurological or any clinical features. Channel variants showed a consistent effect on channel deactivation, slowing the rate of channel closure following normal activation. This specific gain‐of‐function feature is likely to underlie the neurological phenotype in our patients. Our data highlight KCNA6 as a novel channelopathy gene associated with early infantile epileptic phenotypes and neurodevelopmental anomalies.
Four‐gene signature based on machine learning filtration could predict prognosis of patients with breast cancer
Authors: Liu Bo , Wang Huina , Wang Xin , Long Junqi , Zhuang Xujie , Ji Xinchan , Zhu Nian , Li Jinmeng , Gao Ting , Zhang Xuehui , Yu Jiangyong , Zhao Shuangtao
Published: November 2022

Background

This study aims to propose a breast cancer prediction model for early diagnosis and prognosis management of breast cancer.

Objective

In order to explore the pathogenesis of breast cancer and develop accurate breast cancer screening and treatment methods, we have used machine‐learning technologies to conduct an in‐depth study of breast cancer genetic data to obtain new breast cancer signature and prognostic prediction models.

Methods

We explored an optimal cluster by unsupervised clustering methods with different expression genes (DEGs) between normal (n = 113) and tumour (n = 1,102) samples. Using least absolute shrinkage and selection operator (LASSO) regression, we selected four biomarkers to develop a predictive model by Cox regression method in the training set (n = 1,083) and validated its predictive accuracy and independence in the testing sets (n = 2,480). Then Gene Set Enrichment Analysis (GSEA) revealed enriched biological pathways in clusters. Finally, we constructed a nomogram including this signature and other significant risk factors to predict survival rates in patients.

Results

Four mRNAs (CD163L1,QPRT,NKAIN1andTP53AIP1) between two clusters from 4,938 DEGs were identified, and then a four‐gene model (risk scores = 0.454*CD163L1–0.360*NKAIN1 + 0.581*QPRT + 0.788*TP53AIP1) was established to divide patients into high‐ and low‐risk group with significantly different prognosis (p < 0.0001) in the training set. Integrated analysis revealed dysregulated molecular processes including predominantly oncogenic signalling pathway, cell cycle and DNA repair in high‐risk group but enriched metabolism pathway in low‐risk group. In addition, this model had similar predictive value (HR >1.60;p < 0.05) in three independent validation sets, which could predict survival independently with more power compared with single clinical factor. In addition, the nomogram could predict the prognosis of breast cancer patients precisely in the training set and another three testing sets.

Conclusion

This model could predict prognosis of breast cancer patients precisely and independently, and provide evidence to make treatment decisions and design clinical trials.
Absence of ULK1 decreases AMPK activity in the kidney, leading to chronic kidney disease progression
Authors: Yanagi Tomoki , Kikuchi Hiroaki , Susa Koichiro , Takahashi Naohiro , Bamba Hiroki , Suzuki Takefumi , Nakano Yuta , Fujiki Tamami , Mori Yutaro , Ando Fumiaki , Mandai Shintaro , Mori Takayasu , Takeuchi Koh , Honda Shinya , Torii Satoru , Shimizu Shigeomi , Rai Tatemitsu , Uchida Shinichi , Sohara Eisei
Published: November 2022

AMP‐activated protein kinase (AMPK) inactivation in chronic kidney disease (CKD) leads to energy status deterioration in the kidney, constituting the vicious cycle of CKD exacerbation. Unc‐51‐like kinase 1 (ULK1) is considered a downstream molecule of AMPK; however, it was recently reported that the activity of AMPK could be regulated by ULK1 conversely. We demonstrated that AMPK and ULK1 activities were decreased in the kidneys of CKD mice. However, whether and how ULK1 is involved in the underlying mechanism of CKD exacerbation remains unknown. In this study, we investigated the ULK1 involvement in CKD, using ULK1 knockout mice. The CKD model of Ulk1−/− mice exhibited significantly exacerbated renal function and worsening renal fibrosis. In the kidneys of the CKD model of Ulk1−/− mice, reduced AMPK and its downstream β‐oxidation could be observed, leading to an energy deficit of increased AMP/ATP ratio. In addition, AMPK signaling in the kidney was reduced in control Ulk1−/− mice with normal renal function compared to control wild‐type mice, suggesting that ULK1 deficiency suppressed AMPK activity in the kidney. This study is the first to present ULK1 as a novel therapeutic target for CKD treatment, which regulates AMPK activity in the kidney.
A typology of sexism in contemporary business schools: Belligerent, benevolent, ambivalent, and oblivious sexism
Authors: Yarrow Emily , Davies Julie
Published: November 2022

The legitimacy of business schools is based on rankings, revenues, branding, and opportunities to support staff and students “to make a difference in the world”. Yet sexism in business schools is endemic. Drawing on Acker's inequality regimes framework and a thematic analysis of reports in Poets&Quants, EFMD's Global Focus and AACSB International's BizEd/AACSB Insights over a decade, this study explores how business schools are dealing (or not) with sexism. We propose a typology of four categories of sexism in business schools: belligerent, benevolent, ambivalent, and oblivious sexism. Our findings contribute to understandings of institutional theory and the institutional development of business schools as important sites of (sexist and gendered) knowledge production and dissemination and entrenched inequalities. We posit that media constructions of sexism may better inform individual decisions, organizational development, and governance about the imperative to eliminate sexist behaviors and discrimination. We argue that business schools need to gain substantive legitimacy as effective role models by reforming themselves. They must actively tackle institutional and cultural sexism from within. Implications for practice include the effective inclusion of mandatory sexism reporting in international business school accreditation standards and rankings criteria as well as requirements for research funding.