bluuebunny/crossref_metadata_2025 huggingface dataset:
A Multicenter Randomized Comparison of High-Intensity Interval Training and Moderate-Intensity Exercise to Recover Walking Post-Stroke: Results of the HIT-Stroke Trial
Authors: Boyne Pierce , Billinger Sandra A. , Reisman Darcy S. , Awosika Oluwole O. , Buckley Sofia , Burson Jamiah , Carl Daniel , DeLange Matthew , Doren Sarah , Earnest Melinda , Gerson Myron , Henry Madison , Horning Alli , Khoury Jane , Kissela Brett , Laughlin Abigail , McCartney Kiersten , McQuaid Thomas , Miller Allison , Moores Alexandra , Palmer Jacqueline A. , Sucharew Heidi , Thompson Elizabeth , Wagner Erin , Ward Jaimie , Wasik Emily , Whitaker Alicen A. , Wright Henry , Dunning Kari
Published: August 2022

Introduction

For walking rehabilitation after stroke, training intensity and duration are critical dosing parameters that lack optimization. This trial aimed to determine the optimal training intensity (vigorous vs moderate) and minimum training duration (4, 8 or 12 weeks) needed to maximize immediate improvement in walking capacity in chronic stroke.

Methods

Persons with chronic post-stroke gait dysfunction at three centers were randomized to high-intensity interval training (HIT) or moderate intensity aerobic training (MAT), each involving 45 minutes of treadmill and overground walking exercise with a physical therapist, 3 times per week for 12 weeks. The HIT protocol used repeated 30 second bursts of walking at maximum safe speed, alternated with 30-60 second recovery periods, targeting an average aerobic intensity above 60% heart rate reserve (HRR). The MAT protocol used continuous walking with speed adjusted to maintain an initial target of 40 ± 5% HRR, progressing by 5% HRR every 2 weeks, up to 60% HRR as tolerated. Blinded assessment at baseline and after 4, 8 and 12 weeks of training included the 6-minute walk test (6MWT) as the primary measure of walking capacity.

Results

Randomized participants (N=55) attended 1,675 (85%) of 1,980 planned treatment sessions and 197 (90%) of 220 planned testing sessions. No serious adverse events related to study procedures occurred. Compared with MAT, HIT involved significantly higher training speeds (161% vs 96% baseline fastest 10-meter speed, p<0.0001) and mean aerobic intensity (61% vs 46% HRR, p<0.0001) across treatment visits. There was no significant between-group difference in 6MWT changes after 4 weeks of training (HIT +27 meters [95% CI: 6-48], MAT +12 meters [-9-33], p=0.28), but randomization to HIT resulted in significantly greater gains than MAT after 8 weeks (+58 [39-76] vs +29 [9-48] meters, p=0.02) and 12 weeks (+71 [49-94] vs +27 [3-50] meters, p=0.005) of training. HIT also showed significantly greater improvements than MAT on some measures of gait speed, fatigue and exercise capacity.

Discussion

These findings show proof of concept that vigorous training intensity is a critical dosing parameter for walking rehabilitation. In chronic stroke, vigorous walking exercise can produce significant and meaningful gains in walking capacity with only 4 weeks of training, but at least 12 weeks are needed to maximize immediate gains.
Prognostic early snapshot stratification of autism based on adaptive functioning
Authors: Mandelli Veronica , Landi Isotta , Busuoli Elena Maria , Courchesne Eric , Pierce Karen , Lombardo Michael V.
Published: August 2022

A major goal of precision medicine is to predict prognosis based on individualized information at the earliest possible points in development. Using early snapshots of adaptive functioning and unsupervised data-driven discovery methods, we uncover highly stable early autism subtypes that yield information relevant to later prognosis. Data from the National Institute of Mental Health Data Archive (NDA) (n=1,098) was used to uncover 3 early subtypes (<72 months) that generalize with 97% accuracy. Outcome data from NDA (n=2,561; mean age, 13 years) also reproducibly clusters into 3 subtypes with 99% generalization accuracy. Early snapshot subtypes predict developmental trajectories in non-verbal cognitive, language, and motor domains and are predictive of membership in different adaptive functioning outcome subtypes. Robust and prognosis-relevant subtyping of autism based on early snapshots of adaptive functioning may aid future clinical and research work (e.g., clinical trials, intervention), via prediction of these subtypes with our open web-based app (https://landiit.shinyapps.io/vineland_statification_proj/).
Clarifying the role of Cortico-Cortical and Amygdalo-Cortical brain dysconnectivity associated with Conduct Problems
Authors: Dugré Jules R. , Potvin Stéphane
Published: August 2022

Background

Recent evidence suggests that adolescents exhibiting conduct problems (CP) may have disrupted brain connectivity at rest. However, these studies are generally characterized by small sample sizes and differ in terms of neuroimaging methodologies and chosen psychometric scales to assess CP. In parallel, evidence from genetic and structural imaging studies suggests that aggregating measures may increase generalizability and reproducibility in results. Our primary aim was to identify deficits in functional brain connectivity that were replicable across two distinct measures of CP.

Methods

In a large sample of adolescents (n=1416), we assessed the relationship between resting-state functional connectome (including the amygdala bilaterally) and two distinct measures of conduct problems. Positive and negative brain connectivity measures were derived from the intersection of both scales. The utility of these aggregated scores was assessed in comparison with variants of psychopathy and clinical diagnoses.

Results

Psychometrics scales assessing CP were significantly related to 231 & 269 disrupted functional connectivity. Only 21 brain connectivity were shared between the two scales (10 positively and 11 negatively associated with CP. These brain connectivity scores differed between adolescents with variants of psychopathy and healthy controls and were specifically associated with disruptive disorders, but not other pediatric psychiatric disorders.

Conclusion

The current study provides the evidence that different measures of CP may yield distinct results. Nonetheless, it also highlights that functional brain connectivity that intersected between the two scales may be robust and reliable neurobiological markers of severity of CP. Finally, brain connectivity scores may be generalizable to variants of psychopathy and specific to disruptive disorders.
How talin allosterically activates vinculin
Authors: Franz Florian , Tapia-Rojo Rafael , Winograd-Katz Sabina , Boujemaa-Paterski Rajaa , Li Wenhong , Unger Tamar , Albeck Shira , Aponte-Santamaria Camilo , Garcia-Manyes Sergi , Medalia Ohad , Geiger Benjamin , Gräter Frauke
Published: August 2022

The talin-vinculin axis is a key mechanosensing component of cellular focal adhesions. How talin and vinculin respond to forces and regulate one another remains unclear. By combining single molecule magnetic tweezer experiments, Molecular Dynamics simulations, actin bundling assays, and adhesion assembly experiments in live cells, we here discover a two-ways allosteric network within vinculin as a regulator of the talin-vinculin interaction. We directly observe a maturation process of vinculin upon talin binding which reinforces the binding to talin at a rate of 0.03 s−1. This allosteric transition can compete with force-induced dissociation of vinculin from talin only at 7-10 pN. Mimicking the allosteric activation by mutation yields a vinculin molecule that bundles actin and localizes to focal adhesions in a force-independent manner. Hence, the allosteric switch confines talin-vinculin interactions and focal adhesion build-up to intermediate force levels. The ‘allosteric vinculin mutant’ is a valuable molecular tool to further dissect the mechanical and biochemical signalling circuits at focal adhesions and elsewhere.
A conserved isoleucine in the binding pocket of RIG-I controls immune tolerance to mitochondrial RNA
Authors: de Regt Ann Kristin , Anand Kanchan , Ciupka Katrin , Gatterdam Karl , Putschli Bastian , Fusshöller David , Hilbig Daniel , Kirchhoff Alexander , Hunkler Charlotte , Wolter Steven , Grünewald Agathe , Schuberth-Wagner Christine , Ludwig Janos , Paeschke Katrin , Bartok Eva , Zillinger Thomas , Hagelueken Gregor , Hartmann Gunther , Geyer Matthias , Schlee Martin
Published: August 2022

RIG-I is a cytosolic receptor of viral RNA essential for the immune response to numerous RNA viruses. Accordingly, RIG-I must sensitively detect viral RNA yet tolerate abundant self-RNA species. The basic binding cleft and an aromatic amino acid of the RIG-I C-terminal domain(CTD) mediate high-affinity recognition of 5’triphosphorylated and 5’base-paired RNA(dsRNA). Here, we found that, while 5’unmodified hydroxyl(OH)-dsRNA demonstrated residual activation potential, 5’-monophosphate(5’p)-termini, present on most cellular RNAs, prevented RIG-I activation. Determination of CTD/dsRNA co-crystal structures and mutant activation studies revealed that the evolutionarily conserved I875 within the CTD sterically inhibits 5’p-dsRNA binding. RIG-I(I875A) was activated by both synthetic 5’p-dsRNA and endogenous long dsRNA within the polyA-rich fraction of total cellular RNA. RIG-I(I875A) specifically interacted with a long, highly structured, polyA-bearing, non-coding mitochondrial(mt) RNA, and depletion of mtRNA from total RNA abolished its activation. Altogether, our study demonstrates that avoidance of 5’p-RNA recognition is crucial to preventing mtRNA-triggered RIG-I-mediated autoinflammation.
AbBERT: Learning Antibody Humanness via Masked Language Modeling
Authors: Vashchenko Denis , Nguyen Sam , Goncalves Andre , da Silva Felipe Leno , Petersen Brenden , Desautels Thomas , Faissol Daniel
Published: August 2022

Understanding the degree of humanness of antibody sequences is critical to the therapeutic antibody development process to reduce the risk of failure modes like immunogenicity or poor manufacturability. We introduce AbBERT, a transformer-based language model trained on up to 20 million unpaired heavy/light chain sequences from the Observed Antibody Space database. We first validate AbBERT using a novel “multi-mask” scoring procedure to demonstrate high accuracy in predicting complementary determining regions—including the challenging hypervariable H3 region. We then demonstrate several uses of AbBERT at various points along the antibody design process. AbBERT enhances in silico antibody optimization via deep reinforcement learning by utilizing its learned embeddings as additional observations during optimization. Within a larger computational antibody design platform, AbBERT has been successfully applied as an additional design objective, where it displays strong correlations with computational tools predicting antibody structural stability. Finally, mutant antibody sequences that have been scored as unfavorable by AbBERT have shown corresponding low yields when expressed in cells. These use cases demonstrate the power of language modeling within computational antibody design.
A novel in silico method employs chemical and protein similarity algorithms to accurately identify chemical transformations in the human gut microbiome
Authors: Bustion Annamarie , Agrawal Ayushi , Turnbaugh Peter J. , Pollard Katherine S.
Published: August 2022

Bacteria within the gut microbiota possess the ability to metabolize a wide array of human drugs, foods, and toxins, but the responsible enzymes for these chemical events remain largely uncharacterized due to the time consuming nature of current experimental approaches. Attempts have been made in the past to computationally predict which bacterial species and enzymes are responsible for chemical transformations in the gut environment, but with low accuracy due to minimal chemical representation and sequence similarity search schemes. Here, we present an in silico approach that employs chemical and protein Similarity algorithms that Identify MicrobioMe Enzymatic Reactions (SIMMER). We show that SIMMER predicts the chemistry and responsible species and enzymes for a queried reaction with high accuracy, unlike previous methods. We demonstrate SIMMER use cases in the context of drug metabolism by predicting previously uncharacterized enzymes for 88 drug transformations known to occur in the human gut. Bacterial species containing these enzymes are enriched within human donor stool samples that metabolize the query compound. After demonstrating its utility and accuracy, we chose to make SIMMER available as both a command-line and web tool, with flexible input and output options for determining chemical transformations within the human gut. We present SIMMER as a computational addition to the microbiome researcher’s toolbox, enabling them to make informed hypotheses before embarking on the lengthy laboratory experiments required to characterize novel bacterial enzymes that can alter human ingested compounds.
Global convergence of dominance and neglect in flying insect diversity
Authors: Srivathsan Amrita , Ang Yuchen , Heraty John M. , Hwang Wei Song , Jusoh Wan F.A. , Kutty Sujatha Narayanan , Puniamoorthy Jayanthi , Yeo Darren , Roslin Tomas , Meier Rudolf
Published: August 2022

Most of arthropod biodiversity is unknown to science. For this reason, it has been unclear whether insect communities around the world are dominated by the same or different taxa. This question can be answered through standardized sampling of biodiversity followed by estimation of species diversity and community composition with DNA sequences. This approach is here applied to flying insects sampled by 39 Malaise traps placed in five biogeographic regions, eight countries, and numerous habitats (>220,000 specimens belonging to >25,000 species in 463 families). Unexpectedly, we find that 20 insect families account for >50% of local species diversity regardless of continent, climatic region, and habitat type. These consistent differences in family-level dominance explain two-thirds of variation in community composition despite massive levels of species turnover, with most species (>97%) in the top 20 families encountered at a single site only. Alarmingly, the same families that dominate global insect diversity also suffer from extreme taxonomic neglect with little signs of increasing activities in recent years. Tackling the biodiversity of these “dark taxa” thereby emerges as an urgent priority because the arthropod groups comprising most of the global flying insect diversity are particularly poorly known.
Loss of TMEM65 causes mitochondrial disease mediated by mitochondrial calcium
Authors: Zhang Yingfan , Reyes Laura , Sun Junhui , Liu Chengyu , Springer Danielle , Noguchi Audrey , Aponte Angel M. , Munasinghe Jeeva , Covian Raul , Murphy Elizabeth , Glancy Brian
Published: August 2022

Transmembrane protein 65 (TMEM65) depletion in a patient carrying a homozygous variant in the Tmem65 splice site resulted in severe mitochondrial encephalomyopathy, indicating the clinical importance of TMEM65. However, the function of TMEM65 remains unknown. Here, we generated a TMEM65 reporter mouse as well as whole-body and tissue-specificTmem65knockout (KO) mice to investigate the localization and function of TMEM65. We show that TMEM65 is localized to mitochondria in heart, skeletal muscle, and throughout the brain. Both whole-body and nervous system-specificTmem65KO result in severe growth retardation and sudden death following seizures ~3 weeks after birth, indicating TMEM65 is indispensable for normal brain function. In addition, we find that skeletal muscle-specificTmem65KO leads to progressive, adult-onset myopathy preceded by elevated mitochondrial calcium levels despite unaltered expression of known mitochondrial or cellular calcium handling proteins. Consistently, we demonstrate that ablation of TMEM65 results in a loss of sodium-dependent mitochondrial calcium export. Finally, we show that blocking mitochondrial calcium entry through removal of the mitochondrial calcium uniporter (MCU) rescues the early lethality of whole-body TMEM65 ablation. Our data not only reveal the essential role of TMEM65 in mammalian physiology, but also suggest modulating mitochondrial calcium may offer a potential therapeutical approach to address defects associated with TMEM65 misexpression.
Concomitant immunity to M. tuberculosis infection
Authors: Joslyn Louis R. , Flynn JoAnne L. , Kirschner Denise E. , Linderman Jennifer J.
Published: August 2022

Some persistent infections provide a level of immunity that protects against reinfection with the same pathogen, a process referred to as concomitant immunity. To explore the phenomenon of concomitant immunity duringMycobacterium tuberculosisinfection, we utilizedHostSim, a previously published virtual host model of the immune response following Mtb infection. By simulating reinfection scenarios and comparing with data from non-human primate studies, we predict that the durability of a concomitant immune response against Mtb is intrinsically tied to levels of tissue resident memory T cells (Trms) during primary infection, with a secondary but important role for circulating Mtb-specific T cells. Further, we compareHostSimreinfection experiments to observational TB studies from the pre-antibiotic era to predict that the upper bound of the lifespan of resident memory T cells in human lung tissue is likely 2-3 years. To the authors’ knowledge, this is the first estimate of resident memory T-cell lifespan in humans. Our findings are a first step towards demonstrating the important role of Trms in preventing disease and suggest that the induction of lung Trms is likely critical for vaccine success.
TP53-dependent CRISPR-Cas9 sex bias across cancer types affects MYC, PIK3CA, and SUV39H1 mediated by factors including SOX9, FOXO4, and PRC1
Authors: Guo Mengbiao , Xiong Yuanyan
Published: August 2022

CRISPR-Cas9 system has emerged as the dominant technology for gene editing and has great potential for large-scale clinical applications. One major concern is its off-target issue and other potential side effects after the introduction of exogenous CRISPR-Cas9 into cells. Several previous studies investigated CRISPR-Cas9 interactions with p53 mainly in non-transformed cells, such as RPE1 (retinal pigmented epithelium cells) and H9 (embryonic stem cells [ESC]). Recently, it has been reported that Cas9 alone can activate the p53 pathway and select for p53-inactivating mutations after studying hundreds of cancer cell lines. We reanalyzed the reported data of Cas9-associated p53-inactivating mutations and observed large significant sex difference when comparing Cas9 activities in p53-wildtype and p53-mutant cell lines. To expand the impact of this finding, we further examined all protein-coding genes screening by the CRISPR-Cas9 system in a large-scale dataset from the DepMap project. We highlight the p53 status-dependent sex bias of CRISPR-Cas9 effect across cancer cell types (genes includingMYC, PIK3CA, KAT2B, KDM4E, SUV39H1, FANCB, TLR7, and APC2) and potential mechanisms (mediated by transcriptional factors including SOX9, FOXO4, LEF1, and RYBP) underlying this phenomenon, which suggest that the p53-dependent sex bias effect may need to be considered in future clinical applications, especially in cancer, when using this genome editing system.
A long interval between priming and boosting SARS-CoV-2 mRNA vaccine doses enhances B cell responses with limited impact on T cell immunity
Authors: Nicolas Alexandre , Sannier Gérémy , Dubé Mathieu , Nayrac Manon , Painter Mark M. , Goel Rishi R. , Laporte Mélanie , Medjahed Halima , Williams Justine C. , Brassard Nathalie , Niessl Julia , Gokool Laurie , Morrisseau Chantal , Arlotto Pascale , Tremblay Cécile , Martel-Laferrière Valérie , Finzi Andrés , Greenplate Allison R. , Wherry E. John , Kaufmann Daniel E.
Published: August 2022

Spacing the first two doses of SARS-CoV-2 mRNA vaccines beyond 3-4 weeks raised initial concerns about vaccine efficacy. While studies have since shown that long-interval regimens induce robust antibody responses, their impact on B and T cell immunity is poorly known. Here, we compare in SARS-CoV-2 naïve donors B and T cell responses to two mRNA vaccine doses administered 3-4 versus 16 weeks apart. After boost, the longer interval results in higher magnitude and a more mature phenotype of RBD-specific B cells. While the two geographically distinct cohorts present quantitative and qualitative differences in T cell responses at baseline and after priming, the second dose led to convergent features with overall similar magnitude, phenotype and function of CD4+ and CD8+ T cell responses at post-boost memory timepoints. Therefore, compared to standard regimens, a 16-week interval has a favorable impact on the B cell compartment but minimally affects T cell immunity.
Detection of a GLIS3 fusion in an infant with AML refractory to chemotherapy
Authors: Smith Stephen M. , Lee Alex G. , Tong Schuyler , Leung Stanley G. , Hongo Henry , Rivera Jose M. , Sweet-Cordero E. Alejandro , Michlitsch Jennifer , Stieglitz Elliot
Published: August 2022

Infants diagnosed with acute myeloid leukemia (AML) frequently harbor cytogenetically cryptic fusions involving KMT2A, NUP98, or GLIS2. Those with AML driven specifically by CBFA2T3::GLIS2 fusions have a dismal prognosis and are currently risk-stratified to receive hematopoietic stem cell transplantation (HSCT) in first remission. Here we report an infant with AML who was refractory to multiple lines of chemotherapy but lacked an identifiable fusion despite cytogenetic, fluorescence in situ hybridization (FISH) and targeted next generation sequencing (NGS) testing. Research-grade RNA-seq from a relapse sample revealed in-frame CBFA2T3::GLIS3 and GLIS3::CBFA2T3 fusions. A patient-derived xenograft (PDX) generated from this patient has a short latency period and represents a strategy to test novel agents that may be effective in this aggressive subtype of AML. This report describes the first case of AML with a CBFA2T3::GLIS3 fusion and highlights the need for unbiased NGS testing including RNA-seq at diagnosis, as patients with CBFA2T3::GLIS3 fusions should be considered for HSCT in first remission.
Large deviations for the stochastic functional integral equation with nonlocal condition
Authors: Shruthi Gopal , Suvinthra Murugan
Published: August 2022

Purpose

The purpose of this paper is to study large deviations for the solution processes of a stochastic equation incorporated with the effects of nonlocal condition.

Design/methodology/approach

A weak convergence approach is adopted to establish the Laplace principle, which is same as the large deviation principle in a Polish space. The sufficient condition for any family of solutions to satisfy the Laplace principle formulated by Budhiraja and Dupuis is used in this work.

Findings

Freidlin–Wentzell type large deviation principle holds good for the solution processes of the stochastic functional integral equation with nonlocal condition.

Originality/value

The asymptotic exponential decay rate of the solution processes of the considered equation towards its deterministic counterpart can be estimated using the established results.
Critical plane-based fatigue life model under multiaxial random loading
Authors: Wang Jie , Liu Jianhui , Hua Feilon , He Yingbao , Wang Xuexue
Published: August 2022

Purpose

Engineering components/structures are usually subjected to complex and variable loads, which result in random multiaxial stress/strain states. However, fatigue analysis methods under constant loads cannot be directly applied to fatigue life prediction analysis under random loads. Therefore, the purpose of this study is how to effectively evaluate fatigue life under multiaxial random loading.

Design/methodology/approach

First, the average phase difference is characterized as the ratio of the number of shear strain cycles to the number of normal strain cycles, and the new non-proportional additional hardening factor is proposed. Then, the determined random typical load spectrum is processed into a simple variable amplitude load spectrum, and the damage in each plane is calculated according to the multiaxial fatigue life prediction model and Miner theory. Meanwhile, the cumulative damage can be calculated separately by projection method. Finally, the maximum projected cumulative damage plane is defined as the critical plane of multiaxial random fatigue.

Findings

The fatigue life prediction capability of the method is verified based on test data of TC4 titanium alloy under random multiaxial loading. Most of the predicting results are within double scatter bands.

Originality/value

The objective of this study is to provide a reference for the determination of critical plane and non-proportional additional hardening factor under multiaxial random loading, and to promote the development of multiaxial fatigue from experimental studies to practical engineering applications.
Does the deployment of algorithms combined with direct electronic access increase conduct risk? Evidence from the LME
Authors: Culley Alexander Conrad
Published: August 2022

Purpose

The purpose of this paper is to examine the effectiveness of two regulatory initiatives in developing awareness of conduct risk associated with algorithmic and direct-electronic access (DEA) trading at broker-dealers: the UK Financial Conduct Authority’s algorithmic trading compliance in the wholesale markets and Commission Delegated Regulation 2017/589 (CDR 589) to the second Markets in Financial Instruments Directive.

Design/methodology/approach

A qualitative examination of 15 semi-structured interviews with representatives of London Metal Exchange member firms, their clients and regulators.

Findings

This paper finds that the key conduct related messages in algorithmic trading compliance in the wholesale markets may not yet be fully embedded at broker–dealers. This is because of a perceived simplicity of the algorithms deployed by broker dealers or, alternatively, a lack of reflection on their impact. Conversely, a concern exists that clients’ deployment of algorithms on DEA channels provided by broker–dealers increase conduct risk. However, the threat of harm posed by clients is not envisaged in current definitions of conduct risk. Accordingly, CDR 2017/589 does not currently require firms to evaluate clients’ awareness of it.

Research limitations/implications

This study’s findings are limited to the insights provided by 15 participants.

Originality/value

This paper contributes to existing research by deepening understanding of conduct risk arising from algorithmic trading and DEA. To account for the potential harm arising from clients’ activities, this paper proposes a revision to Miles’s definition of conduct risk. This is complemented by a proposed amendment to CDR 2017/589 to require evaluation of clients’ understanding of conduct risk.
Disentangling the elements of PsyCap as drivers for work, organization and social engagement in knowledge-intensive work
Authors: Toth Ilona , Heinänen Sanna , Kianto Aino
Published: August 2022

Purpose

In response to a growing interest in worker well-being in a work-life which is experiencing fundamental transformations, this paper builds and tests a research model on the role of psychological capital (PsyCap) in three different forms of engagement at work. Engagement at work has been identified as one of the most significant drivers of successful work performance.

Design/methodology/approach

Using a quantitative research design, data were collected from 396 highly specialized knowledge workers through anonymous questionnaires. Research hypotheses were tested with linear models.

Findings

Analysis results indicate that all three forms of engagement are affected by PsyCap which consists of self-efficacy, resilience, hope and optimism, but the effect of individual dimensions is not the same for different forms of engagement at work.

Practical implications

It is argued that paying more attention to personal resources, such as the dimensions of PsyCap, and acknowledging diversity among individual workers offer possibilities for increasing employee performance. HR personnel can benefit organizational performance by boosting different dimensions of employees’ PsyCap for different engagement purposes.

Originality/value

This paper takes a wider perspective on engagement at work, arguing that also organization engagement and social engagement, together with work engagement, are important factors for employee well-being and performance in work society.
Literature review as a key step in research processes: case study of MA dissertations written on EFL of Saudi context
Authors: Alsalami Ahmed Ibrahim
Published: August 2022

Purpose

The aim of this study is to find out the most common types of literature review and the accuracy of citing information related to topic in question among Saudi English as a Foreign Language (EFL) postgraduate students at Al-Baha University. This study also aims at revealing the quality of the literature review written by researchers.

Design/methodology/approach

This qualitative study used content analysis to investigate 15 unpublished Master of Arts (MA) dissertations written on EFL of Saudi context. They were analyzed qualitatively using criteria modified from Snyder's (2019) model which is considered a potential method for making theoretical and practical contributions of literature review.

Findings

The findings of the study showed that students favored the systematic review over the integrative. Additionally, data showed that students were lacking in paraphrasing and organizing cited information coherently and appropriately. Moreover, students' performance was better in design, conduct, and data abstraction and analysis criterion, whereas they seemed rather weak in structuring and writing the review criteria.

Originality/value

The significance of the study is to provide researchers with methodological guidance and reference to write a comprehensive and appropriate literature review. Based on the findings, this study concluded with some implications that aim to assist researchers in carrying out their studies professionally. Furthermore, the findings provide decision-makers in higher education institutions with important practical implications. In light of the study's findings, it is suggested to carry out further research investigating postgraduate students to find out their perceptions and attitudes regarding the quality standards of scientific research writing and the paraphrasing strategies.
Learning organizations in emerging economies: the effect of knowledge management on innovative culture in Chilean companies
Authors: Acevedo Juan , Diaz-Molina Ivan
Published: August 2022

Purpose

This study aims to explore the impact of knowledge management (KM) on the development of an innovative culture in learning organizations from emerging economies.

Design/methodology/approach

A quantitative study using a survey was carried out, achieving a pooled cross-sectional sample of 10,567 workers, made up of 69 larger Chilean companies.

Findings

Results were analyzed using the exploratory factor analysis and multilevel regression analysis techniques. The findings provide insights into the positive and significant effect of KM – as acquisition, dissemination and responsiveness to knowledge – on innovative culture.

Practical implications

The findings suggest that managers become more successful in their overall innovative efforts when implementing routines of knowledge or know-how practices that generate a learning culture characterized through discovery skills, creativity, empowerment and cooperation.

Originality/value

This is an original study that introduces valuable information on learning organizations in emerging markets, contrasting to traditional literature and frequently focusing on developed countries. This study explains the cultural change in learning organizations through KM’s role, which offers routinization of learning practices to facilitate an innovative culture.
Are progressive chief prosecutors effective in reducing prison use and cumulative racial/ethnic disadvantage? Evidence from Florida
Authors: Mitchell Ojmarrh , Mora Daniela Oramas , Sticco Tracey L. , Boggess Lyndsay N.
Published: August 2022

Research Summary

Progressive chief prosecutors, campaigning on platforms calling for reducing prison populations and racial/ethnic disparities, have been elected in numerous jurisdictions across the United States in recent years. Yet, there is no empirical research that compares case outcomes between jurisdictions headed by progressive and traditional chief prosecutors. In this research, we utilize a cumulative case outcome approach that tracks cases from arrest to disposition to examine whether cases prosecuted under progressive chief prosecutors receive less punitive sanctions and exhibit smaller racial/ethnic disparities. We find that cases adjudicated in progressive jurisdictions are more likely to end without a felony conviction and less likely to result in a prison sentence. Racial but not generally ethnic disadvantage is evident in case outcomes, and racial disparities are smaller in jurisdictions led by progressive chief prosecutors.

Policy Implications

The election of progressive prosecutors is a radical departure from earlier approaches aimed at controlling prison populations and mitigating racial disparities. Instead of restricting the discretion of criminal justice actors, voters are relying on progressive, reformist prosecutors to use their enormous discretion in less punitive and more egalitarian fashions. This research indicates that progressive chief prosecutors do, in fact, reduce prison use and racial disparities.
Comparative safety of Janus kinase inhibitors and tumor necrosis factor inhibitors in patients undergoing treatment for rheumatoid arthritis
Authors: Fang Yao‐Fan , Liu Jia‐Rou , Chang Shu‐Hao , Kuo Chang‐Fu , See Lai‐Chu
Published: August 2022

Objectives

Since 2010, biological disease‐modifying antirheumatic drugs (bDMARDs) have been the dominant mode of treatment for rheumatoid arthritis (RA). However, the safety of DMARDs, such as tumor necrosis factor inhibitors (TNFis) and Janus kinase inhibitors (JAKis), in treating patients with RA is a concern. We compared the safety outcomes of JAKis and TNFis in RA patients in clinical settings.

Methods

Patients diagnosed with RA between 2015 and 2017 were identified from the Taiwan National Health Insurance Research Database and followed till 2018. Propensity score stabilized weighting was used to balance the baseline characteristics of the JAKis and TNFis groups. The incidences of safety outcomes, namely cardiovascular (CV) events, tuberculosis (TB), total hip replacement (THR), total knee replacement (TKR), and all‐cause mortality, were compared between the 2 study groups.

Results

A total of 3179 patients with RA who were administered JAKis (n = 822) and TNFis (n = 2357) were included in this study. The mean follow‐up duration was 2.02 years in the JAKis group and 2.10 in the TNFis group. All‐cause mortality had the highest incidence rate, followed by TKR, THR, CV events, and TB. A lower incidence rate of the study outcomes was observed in the JAKis group than in the TNFis group but without statistical significance.

Conclusion

Comparable safety issues and mortality rates were observed for JAKis and TNFis in RA patients treated in real‐world settings.
The interactions and hierarchical effects of long‐term agricultural stressors on soil bacterial communities
Authors: Mombrikotb Shorok B. , Van Agtmaal Maaike , Johnstone Emma , Crawley Michael J. , Gweon Hyun S. , Griffiths Robert I. , Bell Thomas
Published: August 2022

Soils are subjected to multiple anthropogenic modifications, but the synergistic impacts of simultaneous environmental stressors on below‐ground communities are poorly understood. We used a large‐scale (1152 plots), long‐term (26 years), multi‐factorial grassland experiment to assess the impact of five common agricultural practises (pesticides, herbicide, liming, fertilizers and grazing exclusion) and their interactive effects on the composition and activity of soil microbial communities. We confirmed that pH strongly impacts belowground communities, but further demonstrate that pH strongly mediates the impacts of other management factors. Notably, there was a significant interaction between liming and the effect of pesticide application, with only half of the taxa responding to pesticide being shared in both limed and unlimed treatments. Likewise, nutrient amendments significantly altered bacterial community structure in acidic soils. Not only do these results highlight an hierarchy of effect of commonly used agricultural practices but also the widespread interactions between treatments: many taxa were significantly affected by interactions between treatments, even in the absence of significant main effects. Furthermore, the results demonstrated that chemical amendments may not percolate deeply into physically unperturbed soils with effects concentrated between 0 and 30 cm, despite 20+ years of treatment. The research shows that future changes to agricultural practices will need to consider interactions among multiple factors.
Alteration of plant immunity in the interaction of roots with the endophytic fungus Phomopsis liquidambaris in response to external nitrogen conditions
Authors: Sun Kai , Tang Meng‐Jun , Lu Fan , Peng Da‐Hong , Xu Fang‐Ji , Zhang Wei , Xie Xing‐Guang , Dai Chuan‐Chao
Published: August 2022

The complex environments of plants force them to prioritize their immune responses to stimuli occurring simultaneously, including colonization by microbes or nutrient availability. Little is known about how the interplay between endophytes and nutrient status affects the immune responses of both plants and fungi. We primarily monitored immune responses in rice following inoculation with the endophytic fungus Phomopsis liquidambaris under different nitrogen (N) conditions. Ph. liquidambaris promoted plant growth under low N (LN) conditions, concomitant with higher root colonization. Plant production of oxidative signals, including hydrogen peroxide and nitric oxide, was activated by Ph. liquidambaris colonization under LN conditions, while salicylic acid (SA) was maintained at high levels and was involved in controlling rice‐fungal interactions. High N (HN) conditions enhanced the ability of Ph. liquidambaris in suppressing plant cell death and the ability of roots to degrade Ph. liquidambaris cell walls. Furthermore, under both LN and HN conditions, the activity of plant defence‐associated enzymes and fungal antioxidases was not affected in the interactive association. Our data reveal the alteration of plant immunity, including oxidative signalling and plant cell death, by fungal colonization in response to external N conditions and identify SA signalling as a potential controller for rice‐Ph. liquidambaris interaction.
Different aspects of severe asthma in real life: Role of Staphylococcus aureus enterotoxins and correlation to comorbidities and disease severity
Authors: Caruso Cristiano , Colantuono Stefania , Ciasca Gabriele , Basile Umberto , Di Santo Riccardo , Bagnasco Diego , Passalacqua Giovanni , Caminati Marco , Michele Schiappoli , Senna Gianenrico , Heffler Enrico , Canonica G. Walter , Crimi Nunzio , Intravaia Rossella , De Corso Eugenio , Firinu Davide , Gasbarrini Antonio , Del Giacco Stefano R.
Published: August 2022

Background

Asthma, with several phenotypes and endotypes, is considered particularly suited for precision medicine. The identification of different non‐invasive biomarkers may facilitate diagnosis and treatment. Recently, Staphylococcus aureus and its enterotoxins (SE) have been found to have a role in inducing persistent type 2 airway inflammation in severe asthma, but also in such comorbidities as chronic rhinosinusitis with nasal polyposis (CRSwNP).

Methods

The aim of this retrospective study was to evaluate the prevalence of SE‐IgE sensitization in a multicentric Italian cohort of severe asthmatic patients and correlate it with demographic and clinical characteristics.

Results

A total of 249 patients were included in the analysis, out of which 25.3% were staphylococcal enterotoxin B (SEB)‐IgE positive. We found a meaningful association between SEB‐IgE and female gender, a positive association was also measured between CRS and CRSwNP. No significant association was found between SEB‐IgE sensitization and atopy, the occurrence of exacerbations and corticosteroid dosages. In the SEB‐IgE‐positive patient, blood eosinophil count does not appear to be correlated with the severity of the disease. Patients with SEB‐IgE sensitization are, on average, younger and with an earlier disease onset, thus confirming the possibility to consider SEB‐IgE sensitization as an independent risk factor for developing asthma.

Conclusions

Our data confirm that the search for SE in the initial screening phase of these patients is helpful to better phenotype them, may predict the evolution of comorbidities and lead to a targeted therapeutic choice; in this point of view this represents a goal of precision medicine.
CMT2A‐linked mitochondrial hyperfusion‐driving mutant MFN2 perturbs ER‐mitochondrial associations and Ca2+ homeostasis
Authors: Das Rajdeep , Das Subhrangshu , Chakrabarti Saikat , Chakrabarti Oishee
Published: August 2022

Background Information

Mitofusin2 (MFN2), an important molecular player that regulates mitochondrial fusion, also helps maintain the inter‐organellar contact sites, referred as mitochondria associated membranes (MAMs) that exist between the ER and mitochondria. The study deals with a mutant of MFN2, R364W‐MFN2, linked with the neuropathy, Charcot Marie Tooth (CMT) disease. Previous studies show that this mutant promotes mitochondrial hyperfusion. Here, we try to decipher the role of R364W‐MFN2 in affecting the ER mitochondrial associations at the MAM junctions and inter‐organellar calcium signalling between the ER and the mitochondria.

Results

Our results show that R364W‐MFN2 altered ER‐mitochondria association at the MAM junctions, predisposed mitochondria towards cellular stress with the mitochondria undergoing rapid fission upon induction of mild stress and perturbs inter‐organellar calcium homeostasis.

Conclusion

The results indicate that R364W‐MFN2 not only affects mitochondrial morphology and dynamics but also modulate its interaction with the ER and Ca2+ signalling between the two organelles.

Significance

This study provides significant insight that presence of the R364W‐MFN2 mutation makes cells susceptible towards stress, thus negatively affecting cellular health which altogether might culminate in the form of the CMT neuropathy.
Nardosinone suppresses monoiodoacetate‐induced osteoarthritis in rats: The key role of the miR‐218‐5p/NUMB axis
Authors: Hu Linyong , Luo Dejun , Zhang Hong , He Ling
Published: August 2022

Nardosinone is a bioactive compound with a sesquiterpenoid structure isolated from Nardostachys jatamansi. The compound has shown treatment effects against skeletal disorders. In the current study, the effects of nardosinone on osteoarthritis (OA) were first assessed and the mechanism underlying the effects was explored by detecting changes in the miR‐218‐5p/NUMB axis. The miR, as a potential target mediating the effects of nardosinone on OA, was first determined with microarray and RT‐qPCR detections. Then, OA symptoms were induced in rats using monoiodoacetate (MIA) and treated with nardosinone. The anti‐OA effects of nardosinone were assessed via the detection of the histological structure and inflammation. The role of miR‐218‐5p was delineated by modulating its levels in OA‐affected rats. Based on the results of microarray and RT‐qPCR detections, miR‐218‐5p was selected as the therapeutic target for nardosinone. The induction of OA resulted in tissue destruction and the production of cytokines in rat joint tissues, which was associated with the up‐regulation of miR‐218‐5p and the downregulation of NUMB. For OA‐affected rats treated with nardosinone, the joint structure was improved and the inflammatory response was suppressed, along with the restored expression levels of miR‐218‐5p and NUMB. The re‐induced level of miR‐218‐5p compromised the anti‐OA effects of nardosinone, indicating that the inhibition of the miR played an indispensable role in the anti‐OA function of nardosinone. Collectively, the findings of our study demonstrated that nardosinone exerts treatment effects against OA by modulating the miR‐218‐5p/NUMB axis. Future studies will provide more detailed information on the interaction between nardosinone and miR in the attenuation of OA.
Vulnerable children aiding visually challenged beggars in Nigeria: Need for social work intervention
Authors: Nnama‐Okechukwu Chinwe U. , Ebimgbo Samuel O. , Agha Agha A. , Onalu Chinyere E.
Published: August 2022

The increasing phenomenon of street children aiding visually challenged beggars and the risk factors involved in such activity is of much concern to social workers in Nigeria. With low investment in social protection for vulnerable children, a large number of children are constantly involved in income‐generating activities on the street. This study through in‐depth interviews explored the experiences of children who aid visually challenged beggars in a semi‐urban city in Nigeria. Findings based on lived experiences are thematically discussed in this study. Well‐coordinated social protection measures can keep vulnerable children off the street and within the safety net of their family.
Woody plant phylogenetic diversity supports nature's contributions to people but is at risk from human population growth
Authors: Davies T. Jonathan , Maurin Olivier , Yessoufou Kowiyou , Daru Barnabas H. , Bezeng Bezeng S. , Mankga Ledile T. , Schaefer Hanno , Thuiller Wilfried , van der Bank Michelle
Published: August 2022

The Tree of Life—phylogeny—provides a powerful tool for understanding the processes regulating life's diversity. Conserving the branches on the Tree of Life might also have practical benefits. Using a comprehensive phylogeny of southern African woody trees and shrubs, and structural equation modeling, we show that human population density correlates closely with not only the richness of woody plants in a region but also their evolutionary relatedness. Further, we demonstrate that more phylogenetically diverse species assemblages support a greater diversity of ecosystem goods and services. Our results suggest that people in Africa may gain material benefits from inhabiting regions that support high phylogenetic diversity of woody plants. However, the correlation between human population and woody plant diversity creates a tension between people and biodiversity, which could threaten the contributions to people provided by intact and phylogenetically diverse ecosystems.