bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct bile salt hydrolase substrate preferences dictate C. difficile pathogenesis
Authors: Foley Matthew H. , Walker Morgan E. , Stewart Allison K. , O’Flaherty Sarah , Gentry Emily C. , Allen Garrison , Patel Shakshi , Pan Meichen , Beaty Violet V. , Vanhoy Molly E. , Dougherty Michael K. , McGill Sarah K. , Gulati Ajay , Dorrestein Pieter C. , Baker Erin S. , Redinbo Matthew R. , Barrangou Rodolphe , Theriot Casey M. 
Published: March 2022

Summary paragraphBile acids (BAs) mediate the crosstalk between human and microbial cells and influence intestinal diseases including Clostridioides difficile infection (CDI). While bile salt hydrolases (BSHs) shape the BA pool by deconjugating conjugated BAs, the basis for their substrate preferences and impact on C. difficile remain elusive. Here, we survey the diversity of Lactobacillus BSHs and unravel the structural basis of their substrate preference. We show that leveraging BSH activity and specificity is an effective strategy to prevent C. difficile growth in clinically relevant CDI models. A range of non-canonical conjugated BAs is also identified, comprising unique BSH substrates that also inhibit C. difficile spore germination. These findings establish BSHs as intestinal enzymes essential to BA homeostasis and colonization resistance against C. difficile.One sentence summaryBile salt hydrolase activity inhibits C. difficile by shaping the conventional and non-canonical conjugated bile acid pools
B cell receptor repertoire analysis unveils dynamic antibody response and severity markers in COVID-19 patients
Authors: Rao Soumya , Srivastava Kriti , Verma Anupriya , Das Achintya 
Published: March 2022

ABSTRACTHumoral and cell mediated immunity are critical against viral infections. The knowledge of composition, diversity, gene usage of the B cell repertoires helps in determining the immune response to SARS-CoV-2 infection. Examining B cell response provides insights on therapeutic antibodies, disease severity markers and aids in predicting vaccine response. We have analyzed public domain immunoglobulin sequencing data from PBMCs of SARS-CoV-2 infected individuals to gain a better understanding of B cell repertoire in patients. Public clonotypes showed increased usage of IGHV3, IGHV4, IGKV1, IGKV3, IGLV3 and IGLV2 family genes during the acute phase infection. Identical CDR3 sequences were identified for heavy (H), kappa (K) and lambda (L) chains across individuals, indicating the convergence of B cell selection during SARS-CoV-2 infection. While the immune repertoire dynamically changed over the course of convalescence, there were persistent clones across early and late timepoints. The diversity of antibody repertoire, measured by Shannon-Weiner diversity index for H and K chains, reduced during the acute phase of infection. In addition, the repertoire diversity was low in severe patients compared to patients with mild or moderate symptoms. Increased usage of IGHV4-59 gene was observed in COVID-19 patients with severe symptoms requiring ventilator support at 2 weeks and 3 weeks post symptom onset. IGHV4-59 is reported to have rheumatoid factor (RF) activity with high affinity for IgG and the elevated level of IGHV4-59 provides a potential mechanism for the increased autoimmune responses in severe patients. Correlation of the clinical features with the B cell receptor repertoire dynamics elucidated public antibody clonotypes and disease severity markers for COVID-19.
Target class profiling of small molecule methyltransferases
Authors: Hanson Quinlin M , Shen Min , Guo Hui , Cho Ig-Jun , Hall Matthew D 
Published: March 2022

AbstractTarget class profiling (TCP) is a chemical biology approach to investigating understudied biological target classes. TCP is achieved by developing a generalizable assay platform and screening curated compound libraries to interrogate the chemical biological space of members of an enzyme family with clinical and biological importance. In this work we took a TCP approach to investigate inhibitory activity across a set of small molecule methyltransferases, a subclass of methyltransferase enzymes, with the goal of creating a launchpad to explore this largely understudied target class. Using the representative enzymes nicotinamide N-methyltransferase (NNMT), phenylethanolamine N-methyltransferase (PNMT), histamine N-methyltransferase (HNMT), glycine N-methyltransferase (GNMT), catechol O-methyltransferase (COMT), and guanidinoacetate N-methyltransferase (GAMT), we optimized high-throughput screening (HTS)-amenable assays to screen 27,574 unique small molecules against all targets. From this dataset we identified a novel inhibitor which selectively inhibits the small molecule methyltransferase HNMT, and demonstrated how this platform approach can be leveraged for a targeted drug discovery campaign using the example of HNMT.
Using genome scans to identify genes used repeatedly for adaptation
Authors: Booker Tom R. , Yeaman Sam , Whitlock Michael C. 
Published: March 2022

AbstractAdaptation occurring in similar genes or genomic regions in distinct lineages provides evolutionary biologists with a glimpse at the fundamental opportunities for and constraints to diversification. With the widespread availability of high throughput sequencing technologies and the development of population genetic methods to identify the genetic basis of adaptation, studies have begun to compare the evidence for adaptation at the molecular level among distinct lineages. However, methods to study repeated adaptation are often oriented towards genome-wide testing to identify a set of genes with signatures of repeated use, rather than evaluating the significance at the level of an individual gene. In this study, we propose PicMin, a novel statistical method derived from the theory of order statistics that can test for repeated molecular evolution to estimate significance at the level of an individual gene, using the results of genome scans. This method is generalizable to any number of lineages and indeed, statistical power to detect repeated adaptation increases with the number of lineages that have signals of repeated adaptation of a given gene in multiple lineages. An implementation of the method written for R can be downloaded from https://github.com/TBooker/PicMin.
A cell cycle-linked mechanism for the glutamine driven establishment of stem cell fate
Authors: Xiao Michael , Wu Chia-Hua , Meek Graham , Kelly Brian , Young Lyndsay E.A. , Martire Sara , Castillo Dara Buendia , Saha Purbita , Dube Altair L. , Gentry Matthew S. , Banaszynski Laura A. , Sun Ramon C. , Kikani Chintan K. 
Published: March 2022

AbstractThe cell cycle offers a unique opportunity for stem cells to sample metabolic and signaling cues to establish cell fate. Molecular pathways that integrate and convey these signals to cell cycle machinery to license cell fate transitions and drive terminal differentiation remain unknown. Here, we describe a signaling role of mitochondrial glutamine metabolism in driving exit from cell cycle-linked self-renewal to generate differentiation competent progenitors. In proliferating stem cells, mitochondrial glutamine metabolism opposes the WDR5-linked self-renewal network via acetylation and nuclear translocation of its upstream regulator, PASK. Nuclear PASK disrupts the mitotic WDR5-anaphase-promoting complex (APC/C) interaction to drive exit from self-renewal. Consistent with these roles, loss of PASK or inhibition of glutamine metabolism preserves stemness in vitro and in vivo during muscle regeneration. Our results suggest a mechanism whereby the proliferative functions of glutamine metabolism are co- opted by stem cells to establish cell fate.
Nonlinear EEG signatures of mind wandering during breath focus meditation
Authors: Lu Yiqing , Rodriguez-Larios Julio 
Published: March 2022

AbstractIn meditation practices that involve focused attention to a specific object, novice practitioners often experience moments of distraction (i.e., mind wandering). Previous studies have investigated the neural correlates of mind wandering during meditation practice through Electroencephalography (EEG) using linear metrics (e.g., oscillatory power). However, their results are not fully consistent. Since the brain is known to be a chaotic/nonlinear system, it is possible that linear metrics cannot fully capture complex dynamics present in the EEG signal. In this study, we assess whether nonlinear EEG signatures can be used to characterize mind wandering during breath focus meditation in novice practitioners. For that purpose, we adopted an experience sampling paradigm in which 25 participants were iteratively interrupted during meditation practice to report whether they were focusing on the breath or thinking about something else. We compared the complexity of EEG signals during mind wandering and breath focus states using three different algorithms: Higuchi’s fractal dimension (HFD), Lempel-Ziv complexity (LZC), and Sample entropy (SampEn). Our results showed that EEG complexity was generally reduced during mind wandering relative to breath focus states. We conclude that EEG complexity metrics are appropriate to disentangle mind wandering from breath focus states in novice meditation practitioners, and therefore, they could be used in future EEG neurofeedback protocols to facilitate meditation practice.
Leverage-value nexus in Italian small-medium enterprises: further evidence using dose-response function
Authors: Harasheh Murad , De Vincenzo Francesca 
Published: March 2022

PurposeThe study introduces a new approach to leverage-value relationship. Besides applying the classical regression models, the study deals with leverage as a continuous treatment variable implemented on the firm’s value using the dose-response function (DFR).Design/methodology/approachAfter proper model calibration and splitting the treatment (leverage) into ten doses, a response function is generated, which enables the realization of the dose level at which the firm’s value is maximized. Furthermore, the study tests the pecking order theory (POT) and the trade-off theory (TOT) using the threshold model to see whether firms are under or over-indebted. The analysis is carried out on panel data from small-medium enterprises (SMEs), providing more valuable insights than large and mature companies.FindingsThe study used two leverage measures: total liabilities ratio and bank debt ratio. Value is measured by the market capitalization and Tobin’s Q. In general, the study finds a positive relationship between leverage and value; POT is not strongly supported, firms are below their optimal leverage and there is a certain leverage dose that would maximize firms’ value.Practical implicationsSince the threshold model and DRF show that SMEs are under-indebted, firms could benefit from extra leverage doses without affecting the firm’s risk profile, especially in a low-interest rate regime, and the potential increase in public-private expenditure after Italy obtained the European Recovery Funds.Originality/valueThe study contributes to new knowledge and understanding of financial leverage from new methodological perspectives, offering valuable insights from SMEs using novel approaches.
Exploring the nexus of health promotion, sport and well-being to improve future synergies and public health capacity through integrated approaches
Authors: Sørensen Kristine , Pedersen Lars Steen , Sander Jakob 
Published: March 2022

PurposeNew models of thinking, organization and governance are needed when health systems are under pressure. Inspired by a recent Danish community project called Your Health, this paper sheds light on the nexus of health promotion, sport and well-being, and how an increased focus on synergies can improve public health capacity in the future.Design/methodology/approachThe three areas of interests are presented, and challenges and opportunities are discussed along with the lessons learned from the Danish community project serving as an example of an integrated approach. The project was hosted by a sports club with the aim to enhance the health and well-being of new members, engage volunteers as health motivators and develop new activities in partnership with community organizations.FindingsThe discussion on creating synergies between sport, health promotion and well-being inspired a new model encouraging moving away from silo-thinking towards the sweet-spot where all three perspectives are represented. In this way, public health can be developed to the next level, in particular with regards to actions taking place outside the health sector.Research limitations/implicationsMore research is warranted to develop the evidence that can push for a changed policy agenda and showcase the social and economic return on investments.Practical implicationsThere is a growing interest to support health and well-being. Capacity building is needed to engage non-health stakeholders actively in the health agenda.Originality/valueDespite the need for progress, research is still scarce. Thus, it is important to create a new momentum among relevant stakeholders to facilitate the integration of sport, health promotion and well-being to qualify and expand public health capacity, create better health for all and bridge inequity.
To focus or not: investigating the viability of the “focused factory” concept in firms facing service disruptions
Authors: Parast Mahour Mellat , Oke Adegoke 
Published: March 2022

PurposeIn this paper, the authors draw from the concept of a “focused factory” to examine whether a focused strategy provides superior performance over a non-focused strategy in firms experiencing service disruptions.Design/methodology/approachThe authors test their hypotheses using panel data of the US domestic airline industry from 1998 to 2019.FindingsOverall, the study findings show that a focused strategy provides superior financial performance over a non-focused strategy in both stable environments and unpredictable environments. The authors also find that the effect of service disruptions on profitability is less pronounced for firms following a focused strategy. This shows that focused firms need to grow over time to sustain profitability. Their post hoc analysis shows that for a non-focused strategy (but not for a focused strategy), firm size moderates the effect of service disruptions on profitability. This suggests that a firm pursuing a non-focused strategy can mitigate the negative effect of service disruptions by increasing its size.Originality/valueThis is the first study that examines the effectiveness of the focused strategy in mitigating service disruptions. The results provide further support for the effectiveness of the focused strategy in responding to service disruptions in service organizations.
Large-scale evaluation of a computer-based learning program to increase prison staff knowledge on geriatric and end-of-life care
Authors: Myers Valerie Harwell , Loeb Susan , Kitt-Lewis Erin , Jerrod Tiffany 
Published: March 2022

Purpose
The purpose of this study is to continue research and development of the ECAD-P learning system with an emphasis on developing a scalable unit for testing in a larger number of more diverse correctional settings. There are almost 2.3 million US persons incarcerated. Geriatric and end-of-life (EOL) care in corrections is not as equitable as care in the free world. Technological delivery of geriatric training to staff through computer-based learning (CBL) offers a novel approach to improve care and reduce disparities among those who are most vulnerable during confinement.

Design/methodology/approach
This mixed methods study built an interactive CBL for multidisciplinary staff to address EOL and geriatric issues in prisons. The CBL was iteratively built and tested prior to launching a full-scale evaluation using a pre/post-intervention design.

Findings
Evaluation of the CBL occurred at 7 sites (i.e. 6 state prisons and 1 prison health-care vendor). A total of 241 staff were recruited with 173 completing post-tests. Outcomes were knowledge acquisition regarding care for aging and dying incarcerated persons (i.e. cognitive measure) and attitudes, motivations and values for providing care (i.e. affective measure). Cognitive and affective post-tests were significantly better than at pre-test (all ps < 0.01). ANCOVAs revealed no significant differences for sex or ethnicity.

Originality/value
Outcomes reveal that the CBL is acceptable, feasible and usable in corrections. Staff improved their knowledge after receiving the training. Correctional settings face increasing pressures to better address the health care and management needs of aged, chronically ill and dying incarcerated persons. This e-learning holds promise to contribute to better preparation of corrections staff to effectively care for these populations.
Using augmented reality for shopping: a framework for AR induced consumer behavior, literature review and future agenda
Authors: Riar Marc , Xi Nannan , Korbel Jakob J. , Zarnekow Ruediger , Hamari Juho 
Published: March 2022

PurposeA current technological trend, which has gained even more traction recently due to the COVID-19 pandemic, is the use of augmented reality (AR) in shopping environments. AR is addressing contemporary challenges rooted in online shopping (e.g. in terms of experientiality and try-on) and is fundamentally reshaping consumers' experiences. The purpose of this study is to provide a synthesized and structured overview of the state-of-the-art research focused on AR shopping.Design/methodology/approachThe authors conduct a systematic literature review of the empirical academic corpus focused on shopping via AR technology.FindingsThe review reveals the diverse psychological (cognitive, affective, and social) as well as behavioral outcomes related to the use of AR in the shopping context. The authors integrate the results into a framework for AR induced consumer behavior in shopping, thereby providing an important overview of the dynamics in AR-related shopping and the factors influencing the adoption of the technology by consumers. Specifically, the authors encountered that the technological abilities of AR (e.g. in terms of interactivity, vividness, informativeness, etc.) are a source for enhanced utilitarian and hedonic shopping experiences that can support intentions to purchase a product, reuse an AR app, or recommend it to others. Importantly, our review reveals the demand for several avenues for future research.Originality/valueThe authors provide an overview and synthesis of how and where AR is employed in shopping contexts, what theories and technological characteristics of AR are commonly analyzed, and what psychological and behavioral outcomes AR has been found to evoke. Based on our findings, the authors derive a framework that illustrates the dynamics in AR shopping and give an in-depth discourse on 13 future research agenda points related to thematic, theoretical, methodological, and technological matters.
Impact of workplace safety on employee retention using sequential mediation: evidence from the health-care sector
Authors: Aman-Ullah Attia , Ibrahim Hadziroh , Aziz Azelin , Mehmood Waqas 
Published: March 2022

Purpose
This study aims to examine the impact of workplace safety (WPS) on employee retention (ER) in the health-care sector in Azad Jammu and Kashmir (AJ&K), Pakistan. At the same time, a mediation relationship through job satisfaction (JS) and employee loyalty (EL) was also tested.

Design/methodology/approach
Structured questionnaires were used to collect the data from 300 doctors, using purposive sampling technique analysed using partial least squares (Smart-PLS 3).

Findings
This study’s findings supported all hypotheses, such as WPS has a significant positive relationship with ER. In addition, a mediation relationship between JS and EL was also confirmed. Furthermore, a serial mediation effect of JS and EL between WPS and ER was also confirmed in this study.

Research limitations/implications
This study might not fit organisations from other regions due to regional norms. In the future, this study’s model may be tested on other regions and segments of the health-care sector, such as nurses, management staff and support staff.

Practical implications
The present study is unique because it is based on a newly formulated framework, WPS → JS → EL → ER, under the social exchange theory, which has not been tested before.

Social implications
In a safe environment, doctors will feel relaxed, stay longer and provide better services; resultantly, patients will get better treatment.

Originality/value
This study tested the sequential mediation effect through JS and EL for the first time in ER, which was missing previously, to the best of the authors’ knowledge. This will add more insights to the safety-retention literature in health-care settings. Furthermore, this study is also the first attempt to explore the relationship between WPS and ER in the health-care sector in AJ&K.
Study on the impact behavior of arch micro-strut (ARCH) lattice structure by selective laser melting (SLM)
Authors: Yao Jun , Ding Ruochen , Li Kailun , Du Baorui , Zhao Lu , Yuan Yixiang 
Published: March 2022

Purpose
The purpose of this paper is to identify the energy absorption characteristics of arch micro-strut (ARCH) lattice structure (different from traditional straight micro-strut lattice structure) under high-speed impact, and promote the development of special-shaped micro-strut lattice structure.

Design/methodology/approach
The study serves to study the anti-impact and energy absorption characteristics of ARCH lattice structure under different strain rates and different unit layers of lattice structure. In this paper, quasi-static compression and Hopkinson compression bar experiments are used for comparative analysis.

Findings
The results show that the ARCH lattice structure has obvious strain rate effect. When the strain rate is low, the number of layers of lattice structure has a great influence on the mechanical properties. With the increase of strain rate, the influence of the number of layers on the mechanical properties gradually weakens. So the ARCH lattice structure with fewer layers (less than five layers) should be selected as the impact energy absorbing materials at lower impact rate, while at higher impact rate, the number of layers can be selected according to the actual requirements of components or devices space size.

Originality/value
This study shows that Arch lattice structure has excellent energy absorption performance, and provides a theoretical reference for the application of ARCH lattice structure in energy-absorbing materials. ARCH lattice structure is expected to be applied to a variety of energy absorption and anti-impact components or devices, such as aircraft black box fall buffer components, impact resistant layer of bulletproof and landing buffer device.