bluuebunny/crossref_metadata_2025 huggingface dataset:
Changing patterns of cigarette and ENDS transitions in the US: a multistate transition analysis of youth and adults in the PATH Study in 2015–17 vs 2017–2019
Authors: Brouwer Andrew F. , Jeon Jihyoun , Jimenez-Mendoza Evelyn , Land Stephanie R. , Holford Theodore R. , Friedman Abigail S. , Tam Jamie , Mistry Ritesh , Levy David T. , Meza Rafael
Published: December 2022

Introduction

It is unknown how recent changes in the tobacco product marketplace have impacted transitions in cigarette and electronic nicotine delivery system (ENDS) use.

Methods

A multistate transition model was applied to 24,242 adults and 12,067 youth in Waves 2–4 (2015–2017) and 28,061 adults and 12,538 youth in Waves 4–5 (2017–2019) of the Population Assessment of Tobacco and Health (PATH) Study. Hazards for initiation, cessation, and product transitions were estimated in multivariable models, accounting for gender, age group, race/ethnicity, and daily vs non-daily product use.

Results

Changes in ENDS initiation/relapse rates from never, non-current, and cigarette-only use depended on age group, including among adults. Among youth never users, the 1-year probability of ENDS initiation increased after 2017 from 1.6% (95%CI: 1.4-1.8%) to 3.8% (95%CI: 3.4-4.2). Persistence of ENDS-only use (1-year probability of remaining an ENDS-only user) increased for youth from 40.7% (95%CI: 34.4-46.9%) to 65.7% (95%CI: 60.5-71.1%) and for adults from 57.8% (95%CI: 54.4-61.3%) to 78.2% (95%CI: 76.080.4%). Persistence of dual use similarly increased for youth from 48.3% (95%CI: 37.4-59.2%) to 60.9% (95%CI: 43.0-78.8%) and for adults from 40.1% (95%CI: 37.0-43.2%) to 63.8% (95%CI: 59.6-67.6%). Youth and young adult dual users became more likely to transition to ENDS-only use but middle-aged and older adults did not.

Conclusions

ENDS and dual use have become more persistent. Middle-aged and older adult dual users have become less likely to transition to cigarette-only use but not more likely to discontinue cigarettes. Youth and young adults are more likely to transition to ENDS-only use.
High-dimensional single-cell definition of CLL T cells identifies Galectin-9 as novel immunotherapy target
Authors: Llaó Cid L , Wong JKL , Fernandez Botana I , Paul Y , Wierz M , Flörchinger A , Gonder S , Pagano G , Chazotte M , Bestak K , Schifflers C , Iskar M , Roider T , Czernilofsky F , P-M Bruch , Mallm JP , Cosma A , Campton DE , Gerhard-Hartmann E , Rosenwald A , Colomer D , Campo E , Schapiro D , Dietrich S , Lichter P , Moussay E , Paggetti J , Zapatka M , Seiffert M
Published: December 2022

Failure of cancer immunotherapy is linked to T cell exhaustion. To decipher the underlying mechanisms, we explored the T cell landscape in blood, bone marrow and lymph node samples of patients with chronic lymphocytic leukemia (CLL), and spleen samples of a CLL mouse model. By single-cell RNA-sequencing, mass cytometry (CyTOF), and multiplex image analysis of tissue microarrays, we identified a disease-specific accumulation of distinct regulatory T cell subsets and T cell exhaustion stages and their trajectories in CLL lymph nodes. Integration of T cell receptor sequencing data revealed a clonal expansion of CD8+precursor exhausted T cells (TPEX), suggesting their CLL reactivity. Interactome analyses identified the TIM3 ligand Galectin-9 as a novel immunoregulatory molecule in CLL. Blocking of Galectin-9 in CLL-bearing mice slowed down disease development and reduced the number of TIM3-expressing T cells. Galectin-9 expression correlated with shorter survival of patients with CLL, renal cell carcinoma or glioma.

Statement of significance

Our findings for the first time define the T cell landscape in CLL lymph nodes and reshape the current understanding of T cell exhaustion in this malignancy. They further introduce Galectin-9 as novel immune checkpoint with a high potential to overcome resistance to PD1 targeting drugs in CLL and beyond.
Novel green fluorescent polyamines to analyze ATP13A2 and ATP13A3 activity in the mammalian polyamine transport system
Authors: Houdou Marine , Jacobs Nathalie , Coene Jonathan , Azfar Mujahid , Vanhoutte Roeland , Van den Haute Chris , Eggermont Jan , Daniëls Veronique , Verhelst Steven H. L. , Vangheluwe Peter
Published: December 2022

Cells acquire the polyamines putrescine (PUT), spermidine (SPD) and spermine (SPM)viathe complementary action of polyamine uptake and synthesis pathways. The endosomal P5B-type ATPases ATP13A2 and ATP13A3 emerge as major determinants of mammalian polyamine uptake. Our biochemical evidence shows that fluorescently labeled polyamines are genuine substrates of ATP13A2. They can be used to measure polyamine uptake in ATP13A2 and ATP13A3-dependent cell models resembling radiolabeled polyamine uptake. We further report that ATP13A3 enables faster and stronger cellular polyamine uptake than ATP13A2. We also compared the uptake of new green-fluorescent PUT, SPD and SPM analogs using different coupling strategies (amide, triazole or isothiocyanate) and fluorophores (symmetrical BODIPY, BODIPY-FL and FITC). ATP13A2 promotes the uptake of various SPD and SPM analogs, whereas ATP13A3 mainly stimulates the uptake of PUT and SPD conjugates. However, the polyamine linker and coupling position on the fluorophore impacts the transport capacity, whereas replacing the fluorophore affects polyamine selectivity. The highest uptake in ATP13A2 or ATP13A3 cells is observed with BODIPY-FL-amide conjugated to SPD, whereas BODIPY-PUT analogs are specifically taken upviaATP13A3. We found that P5B-type ATPase isoforms transport fluorescently labeled polyamine analogs with a distinct structure-activity relationship (SAR) suggesting that isoform-specific polyamine probes can be designed.
Fern cell walls and the evolution of arabinogalactan-proteins in streptophytes
Authors: Mueller Kim-Kristine , Pfeifer Lukas , Schuldt Lina , Szövényi Péter , de Vries Sophie , de Vries Jan , Johnson Kim L. , Classen Birgit
Published: December 2022

Significant changes have occurred in plant cell wall composition during evolution and diversification of tracheophytes. As the sister lineage to seed plants, knowledge on the cell wall of ferns is key to track evolutionary changes across tracheophytes and to understand seed plant-specific evolutionary innovations. Fern cell wall composition is not fully understood, including limited knowledge of glycoproteins such as the fern arabinogalactan-proteins (AGPs). Here, we characterize the AGPs from the leptosporangiate fern generaAzolla,SalviniaandCeratopteris. The carbohydrate moiety of seed plant AGPs consists of a galactan backbone including mainly 1,3- and 1,3,6-linked pyranosidic galactose, which is conserved across the investigated fern AGPs. Yet, unlike AGPs of angiosperms, those of ferns contained the unusual sugar 3-O-methylrhamnose. Besides terminal furanosidic Ara (Araf), the main linkage type of Arafin the ferns was 1,2-linked Araf, whereas in seed plants 1,5-linked Arafis often dominating. Antibodies directed against carbohydrate epitopes of AGPs supported the structural differences between AGPs of ferns and seed plants. Comparison of AGP linkage types across the streptophyte lineage showed that angiosperms have rather conserved monosaccharide linkage types; by contrast bryophytes, ferns and gymnosperms showed more variability. Phylogenetic analyses of glycosyltransferases involved in AGP biosynthesis and bioinformatic search for AGP protein backbones revealed a versatile genetic toolkit for AGP complexity in ferns. Our data reveal important differences across AGP diversity which functional significance is unknown. This diversity sheds light on the evolution of the hallmark feature of tracheophytes: their elaborate cell walls.

SIGNIFICANCE STATEMENT

Ferns are the sister lineage of seed plants and key to understanding plant evolution. To understand ferns’ unique cell walls, we analysed arabinogalactan-proteins from the fern generaAzolla,SalviniaandCeratopteris. Comparison of AGP structures throughout the streptophyte lineage reveals special features in relation to systematic positions and proposes a trend to more hydrophilic AGPs in course of evolution. Through comparative genomic analyses, we pinpoint the potential genetic players for this diversity in cell walls.
Identification of broad, potent antibodies to functionally constrained regions of SARS-CoV-2 spike following a breakthrough infection
Authors: Guenthoer Jamie , Lilly Michelle , Starr Tyler N. , Dadonaite Bernadeta , Lovendahl Klaus N. , Croft Jacob T. , Stoddard Caitlin I. , Chohan Vrasha , Ding Shilei , Ruiz Felicitas , Kopp Mackenzie S. , Finzi Andrés , Bloom Jesse D. , Chu Helen Y. , Lee Kelly K. , Overbaugh Julie
Published: December 2022

The antiviral benefit of antibodies can be compromised by viral escape especially for rapidly evolving viruses. Therefore, durable, effective antibodies must be both broad and potent to counter newly emerging, diverse strains. Discovery of such antibodies is critically important for SARS-CoV-2 as the global emergence of new variants of concern (VOC) has compromised the efficacy of therapeutic antibodies and vaccines. We describe a collection of broad and potent neutralizing monoclonal antibodies (mAbs) isolated from an individual who experienced a breakthrough infection with the Delta VOC. Four mAbs potently neutralize the Wuhan-Hu-1 vaccine strain, the Delta VOC, and also retain potency against the Omicron VOCs through BA.4/BA.5 in both pseudovirus-based and authentic virus assays. Three mAbs also retain potency to recently circulating VOCs XBB.1.5 and BQ.1.1 and one also potently neutralizes SARS-CoV-1. The potency of these mAbs was greater against Omicron VOCs than all but one of the mAbs that had been approved for therapeutic applications. The mAbs target distinct epitopes on the spike glycoprotein, three in the receptor binding domain (RBD) and one in an invariant region downstream of the RBD in subdomain 1 (SD1). The escape pathways we defined at single amino acid resolution with deep mutational scanning show they target conserved, functionally constrained regions of the glycoprotein, suggesting escape could incur a fitness cost. Overall, these mAbs are novel in their breadth across VOCs, their epitope specificity, and include a highly potent mAb targeting a rare epitope outside of the RBD in SD1.

Significance Statement

SARS-CoV-2 infections can result in diverse clinical outcomes, including severe disease. Monoclonal antibodies (mAbs) have been used therapeutically to treat infection, but the emergence of variants has compromised their efficacy. Thus, identifying mAbs that are more durable in the face of SARS-CoV-2 evolution is a pressing need. Here, we describe four new mAbs isolated from a Delta-breakthrough infection, that can potently neutralize diverse variants, including multiple Omicron variants. In addition, one mAb shows broader activity against coronaviruses. The breadth of these mAbs is due to their focus on highly conserved regions of the viral protein antigen, including regions that are required for the virus to enter the cell. These properties make them promising candidates for therapeutic use.
Identification of a regulatory pathway governing TRAF1 via an arthritis-associated non-coding variant
Authors: Wang Qiang , Martínez-Bonet Marta , Kim Taehyeung , Sparks Jeffrey A. , Ishigaki Kazuyoshi , Chen Xiaoting , Sudman Marc , Aguiar Vitor , Hernandez Marcos Chiñas , Wactor Alexandra , Wauford Brian , Marion Miranda C. , Gutierrez-Arcelus Maria , Bowes John , Eyre Stephen , Nordal Ellen , Prahalad Sampath , Rygg Marite , Videm Vibeke , Raychaudhuri Soumya , Weirauch Matthew T. , Langefeld Carl D. , Thompson Susan D. , Nigrovic Peter A.
Published: December 2022

TRAF1/C5 was among the first loci shown to confer risk for inflammatory arthritis in the absence of an associated coding variant, but its genetic mechanism remains undefined. Using ImmunoChip data from 3,939 juvenile idiopathic arthritis (JIA) patients and 14,412 controls, we identified 132 plausible common non-coding variants, reduced serially by SNP-seq, electrophoretic mobility shift, and luciferase studies to the single variant rs7034653 in the third intron ofTRAF1. Genetically manipulated experimental cells and primary monocytes from genotyped donors establish that the risk G allele reduces binding of Fos-Related Antigen 2 (FRA2), resulting in reduced TRAF1 expression and enhanced TNF production. Conditioning on this variant eliminates attributable risk for rheumatoid arthritis, implicating a mechanism shared across the arthritis spectrum. These findings reveal that rs7034653, FRA2, and TRAF1 mediate a pathway through which a non-coding causal variant drives risk of inflammatory arthritis in children and adults.
Accuracy-speed-stability trade-offs in a targeted stepping task are similar in young and older adults
Authors: Muijres Wouter , Arnalsteen Sylvie , Daenens Cas , Afschrift Maarten , De Groote Friedl
Published: December 2022

Background

Stepping accuracy, speed, and stability are lower in older compared to young adults. Lower stepping performance in older adults may be due to larger accuracy-speed-stability trade-offs because of reduced ability to simultaneously fulfill these task-level goals. Our goal was to evaluate whether trade-offs are larger in older compared to young adults in a targeted stepping task. Since sensorimotor function declines with age, our secondary goal was to evaluate whether poorer sensorimotor function was associated with larger trade-offs.

Methods

25 young (median 22 years old) and 25 older (median 70 years old) adults stepped into projected targets in conditions with various levels of accuracy, speed, and stability requirements. We determined trade-offs as the change in performance, i.e. foot placement error, step duration, and mediolateral center of pressure path length, between each of these conditions and a control condition. To assess age-related differences in the magnitude of trade-offs, we compared the change in performance between age groups. Associations between trade-offs and measures of sensorimotor function were tested using correlations.

Results

We found an accuracy-speed and an accuracy-stability trade-off in both young and older adults, but trade-offs were not different between young and older adults. Inter-subject differences in sensorimotor function could not explain inter-subject differences in trade-offs.

Conclusion

Age-related differences in the ability to combine task-level goals do not explain why older adults stepped less accurate and less stable than young adults. However, lower stability combined with an age-independent accuracy-stability trade-off could explain lower accuracy in older adults.
Structure of Phosphorylated-like ClpXP Adaptor RssB Reveals an Interface Switch for Activation
Authors: Brugger Christiane , Schwartz Jacob , Filipovski Martin , Deaconescu Alexandra M.
Published: December 2022

In γ-proteobacteria such asEscherichia coli, the general stress response is mediated by σs, the stationary phase dissociable promoter specificity subunit of RNA polymerase. σsis degraded by ClpXP during active growth in a process dependent on the RssB adaptor, which acts catalytically and is thought to be stimulated by phosphorylation of a conserved aspartate in its N-terminal receiver domain. Here we present the crystal structure of full-length RssB bound to a beryllofluoride phosphomimic. Compared to the inhibited IraD anti-adaptor-bound RssB structure, our study reveals movements and coil-to-helix transitions in the C-terminal region of the RssB receiver domain and in the inter-domain segmented helical linker, accompanied by packing of the C-terminal effector domain onto the α4-β5-α5 (4-5-5) “signaling” face of the RssB receiver domain. This face is often the locus of protein-protein interactions in unphosphorylated receiver domains, but its masking is unusual in their phosphorylated forms. Our structure emphasizes the remarkable plasticity that underpins regulatory strategies within the large family of response regulators.
Molecular profiling in HNSCC patients targets potential responsiveness to ICIs
Authors: Sacconi Andrea , Muti Paola , Pulito Claudio , Pellini Raul , Strano Sabrina , Bossi Paolo , Blandino Giovanni
Published: December 2022

Immunotherapy is emerging as a valid therapeutic strategy for various cancers although only a subset of patients responding to the therapy. The response to immunotherapy remains low for many cancer types because of poor ability to appropriately classify responding patients.

We analyzed TCGA cohort of HNSCC patients in relation to a 26 immune gene set and cell types to define signaling pathways associated with resistance to immune checkpoint blockade. Results were validated on a cohort of 102 HNSCC patients under treatment with PD-L1 inhibitors and byin vitroexperiments.

Using bioinformatic approach, we observed a significant association between the gene set and TP53 gene status and other predictors of ICIs’ response in HNSCC patients. The presence of both TP53 mutation and co-mutations was associated with significantly higher levels of the immune gene expression than in lesions with only the TP53 mutated. We also observed that higher level of a MYC signature was associated with lower level of the immune gene expression.In vitroand cohort validation corroborated the evidence.

SIGNIFICANCE

Immune gene signature sets represent biomarkers to be implemented for the better classification of those HNSCC patients responsive to immunotherapy. A particular advantage of these biomarkers is the ability to characterize HNSCC patients using tumor tissues easily applicable in clinical setting.
A somatic hypermutation–based machine learning model stratifies individuals with Crohn's disease and controls
Authors: Safra Modi , Werner Lael , Peres Ayelet , Polak Pazit , Salamon Naomi , Schvimer Michael , Weiss Batia , Barshack Iris , Shouval Dror S. , Yaari Gur
Published: December 2022

Crohn's disease (CD) is a chronic relapsing–remitting inflammatory disorder of the gastrointestinal tract that is characterized by altered innate and adaptive immune function. Although massively parallel sequencing studies of the T cell receptor repertoire identified oligoclonal expansion of unique clones, much less is known about the B cell receptor (BCR) repertoire in CD. Here, we present a novel BCR repertoire sequencing data set from ileal biopsies from pediatric patients with CD and controls, and identify CD-specific somatic hypermutation (SHM) patterns, revealed by a machine learning (ML) algorithm trained on BCR repertoire sequences. Moreover, ML classification of a different data set from blood samples of adults with CD versus controls identified that V gene usage, clusters, or mutation frequencies yielded excellent results in classifying the disease (F1 > 90%). In summary, we show that an ML algorithm enables the classification of CD based on unique BCR repertoire features with high accuracy.
Structures of permuted halves of a modern ribose-binding protein
Authors: Michel Florian , Shanmugaratnam Sooruban , Romero-Romero Sergio , Höcker Birte
Published: December 2022

Periplasmic binding proteins (PBPs) are a class of proteins that participate in the cellular transport of various ligands. They have been used as model systems to study mechanisms in protein evolution, such as duplication, recombination and domain swapping. It has been suggested that PBPs evolved from precursors half their size. Here, the crystal structures of two permuted halves of a modern ribose-binding protein (RBP) from Thermotoga maritima are reported. The overexpressed proteins are well folded and show a monomer–dimer equilibrium in solution. Their crystal structures show partially noncanonical PBP-like fold type I conformations with structural deviations from modern RBPs. One of the half variants forms a dimer via segment swapping, suggesting a high degree of malleability. The structural findings on these permuted halves support the evolutionary hypothesis that PBPs arose via a duplication event of a flavodoxin-like protein and further support a domain-swapping step that might have occurred during the evolution of the PBP-like fold, a process that is necessary to generate the characteristic motion of PBPs essential to perform their functions.
The moderating impact of auditor industry specialisation on the relationship between fair value disclosure and audit fees: empirical evidence from Jordan
Authors: Alharasis Esraa Esam , Prokofieva Maria , Clark Colin
Published: December 2022

Purpose

This paper investigates the application of the product differentiation and shared efficiency approaches to understand the impact of the auditor industry specialisation (IS) on audit fees in relation to Fair Value Disclosures (FVD).

Design/methodology/approach

The study uses 1,470 firm-year observations for the period 2005–2018 and is focused on Jordanian financial firms. Two competing theoretical approaches of IS proxied by audit fee-based measures were employed: firstly, the product differentiation approach measured using Market Share-based (MS) measure and secondly, the shared efficiency approach measured using Portfolio Share-based (PS) measure. The paper employs the Ordinary Least Squares regression to test the association between the proportion of fair-valued assets (using fair value hierarchy inputs) and audit fees.

Findings

The results suggest that the association between the proportion of fair-valued assets and audit fees is strengthened (weakened) when the client hires specialist auditors identified by MS (PS). This association varied across the fair value inputs. Level 1 assets were found to be only moderated by both scenarios positively (negatively) for MS (PS) experts. The results are robust after controlling the endogeneity of auditor self-selection.

Practical implications

The results provide valuable insights for policymakers into challenges of auditing FVD. These insights present a valuable input for the development of FVD policies and practices as well as providing guidance for updating auditor prices. Additionally, the results provide a foundation for policymakers and regulators to introduce and update fair value auditing practices. The current findings are generalisable to other countries, including the Middle East and North Africa, and are particularly beneficial for those countries which have adopted the fair value model.

Originality/value

This study contributes to the theory by demonstrating the impact of the auditor industry expertise on post-implementation costs of FVD. The novelty of the study lies in introducing principle-based standards requirements of FVD to test the relationship. This approach is based on the IFRS disclosure requirements using data from the Jordanian financial sector to examine this relationship.
Improving automated pallet handling procedures at a Saudi milk factory through overall equipment effectiveness
Authors: Alnounou Reham Tarek , Asiri Rawan Ahmed , Alhindi Sara Ayman , Shams Layan Marwan , Ali Sadia Samar , Özceylan Eren
Published: December 2022

Purpose

Saudi Arabia's 2030 vision targets an increase of 34% in non-oil revenue participation in the GDP, thus the need for automation and digital transformation. The Company ER is a market leader producing high-quality dairy products in the Kingdom and is a pioneer in the production industry. The company has recently increased the capacity of its milk factory to meet its vision. An investment was made to automate the pallet handling procedures at the milk factory to provide increased production for daily consumption. The new automation transition in Company ER's milk factory provides a unique opportunity to utilize lean management tools to improve the current automated processes before commercialization.

Design/methodology/approach

OEE (overall equipment effectiveness) will monitor losses for different operational losses in the new automated system and indicate system improvements, with 85% as the target. Based on DMADV (design, measure, analyze, design and validate) methodology, this study analyzes the entire automated pallet handling system. It uses lean tools to identify areas for improvement, identify waste elements and propose solutions to achieve Company ER's OEE targets.

Findings

In this paper, the outcomes will be presented as documented solutions that address the losses encountered in the production system, showing a 12.8% increase in the system's OEE.

Research limitations/implications

Owing the time and resource constraint, this study only involved automated pallet handling procedures in a milk production facility. Hence, the generalization of the result is slightly limited. More studies in several different processes and sectors are required.

Practical implications

This study provided a valuable tool for researchers for gaining deeper understanding regarding the lean manufacturing and its implementation. For practitioners, it is useful to evaluate the degree of lean manufacturing tools in their material handling systems.

Originality/value

This study is the first attempt to develop lean manufacturing constructs for evaluating the automated pallet handling procedures in a milk production facility.
Nonlinear dynamic analysis of wrinkled membrane structure
Authors: Liu Xiang , Cai G.P.
Published: December 2022

Purpose

This paper studies the nonlinear dynamics of membrane structure considering wrinkling effect. The coupling between wrinkles and vibration is investigated elaborately, and new insight on the dynamics of wrinkled membrane is unveiled.

Design/methodology/approach

Based on the stability theory of plates and shells, the wrinkling model of the membrane structure is established. Considering the effects of wrinkling and nonlinearity, the dynamic response is calculated with NewMark method.

Findings

Wrinkling will impact the dynamics of the membrane structure significantly for asymmetrical tension loading cases, dynamic response of the wrinkled membrane structure can be classified into three categories: when the vibration is small, the dynamics of the wrinkled membrane structure will behave linearly, and the wrinkles will only affect the dynamic properties as initial conditions; when the vibration is relatively large, the wrinkles will interact with the vibration during the dynamic process, and the dynamics of the structure shows very complex features; when the vibration is large enough, the dynamics will be dominated by the geometric nonlinearity of large-amplitude vibration.

Originality/value

In the previous works on dynamics of wrinkled membrane structure, only the vibration modes have been studied, which means all those investigations are confined with linear vibration; little research has been conducted on the nonlinear dynamics of wrinkled membrane structure. In view of this, this paper presents an investigation of dynamic properties of membrane structure considering the wrinkling and geometric nonlinear effects. This research work presents some novel discoveries on the nonlinear dynamics of wrinkled membrane.
Past for Future – museums as a digitalized “interaction platform” for value co-creation in tourism destinations
Authors: Massari Francesco Saverio , Del Vecchio Pasquale , Degl'innocenti Eva
Published: December 2022

Purpose

This paper aims to explore how digital technologies can transform the museum into an “interaction platform” able to play a key role in the value co-creation processes of the tourism destination.

Design/methodology/approach

The paper applies the “co-creation through interactions” perspective by Ramaswamy and Ozcan. Empirically, the paper is based on the methodology of single case study identified in MArTA, the well-known National Archeological Museum of Taranto (South Italy). Data collection has been implemented through interviews with key informants and secondary data related to online interviews, press release and reports.

Findings

Findings provide empirical evidence about the contribution that a digitalization strategy can create a “museum as a platform” in which the interactions between the museum, its stakeholders and other co-creation elements (interfaces, artifacts and processes) bring benefits in terms of tourism experiences and sustainable development of the destination.

Practical implications

This research highlights the cultural changes and the actions that museum management has to implement to properly benefit from digitalization and to transform the museum into a reference point for reflection and innovation.

Originality/value

Elements of originality can be found in (1) the exploration of the wide spectrum of benefits and innovations that digital technologies can offer to the museum-mediated interactions and (2) the contribution to the understanding of the museum as a digitalized “interaction platform” capable of supporting the processes of co-creation of value in the complex network of actors and objects of a tourism destination.
The pandemic did not interrupt LA’s violence interrupters
Authors: Ren Jiaoying , Santoso Karina , Hyde David , Bertozzi Andrea L. , Brantingham P. Jeffrey
Published: December 2022

Purpose

The impact of the COVID-19 pandemic on crime has been highly variable. One possible source of variation runs indirectly through the impact that the pandemic had on groups tasked with preventing and responding to crime. Here, this paper aims to examine the impact of the pandemic on the activities undertaken by front-line workers in the City of Los Angeles Mayor’s Office of Gang Reduction and Youth Development (GRYD).

Design/methodology/approach

The authors use both autoregressive integrated moving average modeling and a regression-based event study design to identify changes in GRYD Community Intervention Worker proactive peacemaking and violence interruption activities induced by the onset of the City of Los Angeles “safter-at-home” lockdown.

Findings

Analyses show that the proactive peacemaking and violence interruption activities either remained stable or increased with the onset of the lockdown.

Originality/value

While the City of Los Angeles exempted GRYD’s Community Intervention Workers from lockdown restrictions, there was no guarantee that proactive peacemaking and violence interruption activities would continue unchanged. The authors conclude that these vital functions were indeed resilient in the face of major disruptions to daily life presented by the pandemic. However, the causal connection between stability in Community Intervention Worker activities and gang-related crime remains to be evaluated.
Home‐field advantage meets priming effect in root decomposition: Implications for belowground carbon dynamics
Authors: Zheng Jiajia , Li Shenggong , Wang Huimin , Dai Xiaoqin , Meng Shengwang , Jiang Lei , Ma Ning , Yan Han , Fu Xiaoli , Kou Liang
Published: December 2022

Home‐field advantage (HFA) states that litter decomposes faster in “home” than in “away” soil, due to the specialization of decomposer organisms in decomposing litter derived from their local plant community. Demonstration of the HFA effect has been overwhelmingly based on aboveground leaf litter despite the fact that roots play a pivotal role in carbon (C) and nutrient cycling.

Labile C input in root exudates and newly shed root litters can enhance the activity of soil microorganisms, which in turn can favour the breakdown of older root litter, also referred to as the priming effect. It remains, however, unclear how the addition of fresh root‐derived inputs affects HFA on the decomposition of absorptive roots (ARs) and transport roots (TRs), which have a different chemical composition.

Here, we conducted a two‐stage (endogenous C consumption versus exogenous C priming) reciprocal transplant microcosm experiment to explore the effects of HFA on the decomposition of lower‐quality ARs and higher‐quality TRs of two subtropical tree species (Pinus elliottii and Cunninghamia lanceolata) and their responses to either labile (glucose) or recalcitrant (fresh ARs) C additions.

Decomposition of lower‐quality ARs exhibited neutral HFA, while decomposition of higher‐quality TRs exhibited positive HFA. The absence of HFA for short‐lived ARs was possibly due to the legacy effect of their chemical defences on decomposition. The neutral HFA for ARs became negative with glucose addition, which was linked to the dissimilarity of fungal community between the home and away soils. Neither glucose nor fresh ARs additions changed the HFA pattern of TRs, implying that these long‐lived roots play a reinforced role in soil C accumulation when they decompose away from their origins.

These results indicate that the effect of HFA on decomposition differs between ARs and TRs, and could be modified by the priming effect induced by the root‐derived C input. In general, our findings highlight that complex “HFA‐priming” interactions on root decomposition should be explicitly considered in the paradigm of belowground C dynamics.

Read the free Plain Language Summary for this article on the Journal blog.
Bioactive polyphenols separated from hemp seed shells ameliorate H2O2‐induced oxidative stress injury in human umbilical vein endothelial cells
Authors: Xu Peng‐Wei , Yuan Xiao‐Fan , Zhao Bing
Published: December 2022

In the present study, we investigated the protection of hemp seed polyphenols on human umbilical vein endothelial cells (HUVEC) from H2O2‐mediated oxidative stress injury. Fractions with different polarities were obtained by separating the hemp seed extract using HPD300 macroporous resin‐packed column. The fraction, desorbed by 50% ethanol, is rich in polyphenol (789.51 ± 21.92 mg GAE/g) and has the highest antioxidant activity in vitro. HPLC‐QTOF‐MS/MS identified the main polyphenol components in hemp seed shells: 4 hydroxycinnamic acid amides and 15 lignanamides. The protective effects of hemp seed polyphenol against oxidative‐stress injury in HUVEC cells were evaluated by cell viability, intracellular antioxidant parameters, and cell apoptosis assay. After HUVEC cells were precultured with 50 µg/ml hemp seed polyphenols, the cell viability increased significantly from 53.07 ± 2.46% (model group) to 80.65 ± 1.32% (p < 0.01). In addition, the pretreatment of HUVEC cells with polyphenol could substantially increase their intracellular superoxide dismutase activity and reduce their intracellular reactive oxygen species level, malondialdehyde content, and lactate dehydrogenase leakage index. These findings demonstrate the defensive potential of hemp seed polyphenol in reducing the incidence of cardiovascular disease.

Practical Application

Hemp seed shell waste is produced while producing hemp seed kernel and has abundant phenolic compounds. This research showed that hemp seed polyphenol has potent antioxidant activity in vitro and protects HUVEC cells against H2O2‐induced oxidative stress injury, suggesting that hemp seed polyphenol has the defensive potential to reduce the incidence of cardiovascular disease. These results indicated that polyphenol separated from hemp seed shells is valuable for further research and development, which will improve the utilization rate of hemp seed.
Curcumin suppresses lung cancer progression via circRUNX1 mediated miR‐760/RAB3D axis
Authors: Wu Xiaodan , Chen Hong , Liu Na , Liu Sang , Lin Guanhong
Published: December 2022

Background

Curcumin is a natural chemical component that has an anticancer effect. The aim of this study was to explore the potential molecular mechanism of curcumin regulating lung cancer (LC) progression.

Methods

The expression of circRUNX1, miR‐760 and Ras‐like GTPase 3D (RAB3D) was detected by qRT‐PCR. Cell proliferation were determined by CCK8 assay and colony formation assay. Cell apoptosis, migration and invasion were detected by flow cytometry, wound healing and transwell assays. Protein levels were examined by western blot (WB) analysis. RNA interaction was confirmed by dual‐luciferase reporter assay. LC xenograft tumors were constructed using BALB/c nude mice.

Results

CircRUNX1 was upregulated in LC and its expression could be inhibited by curcumin. Curcumin reduced LC cell proliferation, metastasis, and accelerate apoptosis, while circRUNX1 overexpression reversed these effects. MiR‐760 was confirmed to be a target of circRUNX1, which could reverse the effects of circRUNX1 on curcumin‐treated LC cell functions. RAB3D was a target of miR‐760, and its knockdown reversed the promotion effect of miR‐760 inhibitor on the progression of curcumin‐treated LC cells.

Conclusion

Curcumin suppressed LC progression via circRUNX1/miR‐760/RAB3D axis.
Incidence of primary hepatitis C virus infection among people who inject drugs in Australia pre‐ and post‐unrestricted availability of direct acting antiviral therapies
Authors: Iversen Jenny , Wand Handan , McManus Hamish , Dore Gregory J. , Maher Lisa
Published: December 2022

Aims

The 2016 Global Health Sector Strategy (GHSS) on viral hepatitis aims to reduce new hepatitis C virus (HCV) infections by 80% by 2030, including a 30% reduction by 2020. This study aimed to estimate primary HCV incident infection among a national sample of people who inject drugs (PWID) before and after the introduction of unrestricted access to HCV direct‐acting antiviral (DAA) therapy via Australia's Pharmaceutical Benefits Scheme in 2016.

Design

A simple deterministic linkage method identified repeat respondents in serial cross‐sectional surveys conducted among PWID. Two separate retrospective cohorts of HCV antibody‐negative respondents were created, corresponding to the pre‐ (2010–15) and post‐ (2016–21) DAA time‐periods.

Setting and Participants

This study took place in Australia. Among 757 PWID retained (376 pre‐DAA, 381 post‐DAA), more than half were male (60%), the majority were heterosexual (80%), the median age was 40 years (interquartile range = 33–46 years) and the predominant drugs last injected were heroin (24%), pharmaceutical opioids (27%) and methamphetamine (41%).

Measurements

The primary outcome was HCV seroconversion, defined as a negative HCV antibody test result followed by a positive HCV antibody result. Time to primary incident HCV infection was estimated using the person‐years (PY) method.

Findings

A total 97 of 376 (2010–15) and 41 of 381 (2016–21) HCV seroconversions were identified. Primary HCV incidence more than halved, from 13.6 per 100 PY [95% confidence intervals (CI) = 11.2, 16.6] in 2010–15 to 5.4 per 100 PY (95% CI = 3.9, 7.3) in 2016–21. The decline was independent of observed differences in demographic and drug use characteristics over the two time‐periods (adjusted hazard ratio = 0.47, 95% CI = 0.31–0.69, P < 0.001).

Conclusions

Australia has had a 53% reduction in primary hepatitis C virus (HCV) incidence among people who inject drugs following unrestricted availability of HCV direct acting antiviral therapy in March 2016. Given that PWID are the predominant population at risk of HCV infection in Australia, findings add to the evidence that Australia has probably met its 2020 Global Health Sector Strategy subtarget of a 30% decline in new infections.
Use of Swedish smokeless tobacco during pregnancy: A systematic review of pregnancy and early life health risk
Authors: Brinchmann Bendik C. , Vist Gunn E. , Becher Rune , Grimsrud Tom K. , Elvsaas Ida‐Kristin Ørjasæter , Underland Vigdis , Holme Jørn A. , Carlsen Karin C. Lødrup , Kreyberg Ina , Nordhagen Live S. , Bains Karen Eline Stensby , Carlsen Kai‐Håkon , Alexander Jan , Valen Håkon
Published: December 2022

Background and Aims

Smokeless tobacco is a heterogeneous product group with diverse composition and prevalence globally. Tobacco use during pregnancy is concerning due to the risk of adverse pregnancy outcomes and effects on child health. Nicotine may mediate several of these effects. This systematic review measured health outcomes from Swedish smokeless tobacco (snus) use during pregnancy.

Method

Literature search was conducted by an information specialist in May 2022. We included human studies of snus use during pregnancy compared with no tobacco use, assessed risk of bias, conducted a meta‐analysis and assessed confidence in effect‐estimates using Grading of Recommendations, Assessment, Development and Evaluations (GRADE).

Results

We included 18 cohort studies (42 to 1 006 398 participants). Snus use during pregnancy probably (moderate confidence in risk estimates) increase the risk of neonatal apnea, adjusted odds ratio 95% confidence interval [aOR (95% CI)] 1.96 (1.30 to 2.96). Snus use during pregnancy possibly (low confidence in risk estimates) increase the risk of stillbirths aOR 1.43 (1.02 to 1.99), extremely premature births aOR 1.69 (1.17 to 2.45), moderately premature birth aOR 1.26 (1.15 to 1.38), SGA aOR 1.26 (1.09 to 1.46), reduced birth weight mean difference of 72.47 g (110.58 g to 34.35 g reduction) and oral cleft malformations aOR 1.48 (1.00 to 2.21). It is uncertain (low confidence in risk estimates, CI crossing 1) whether snus use during pregnancy affects risk of preeclampsia aOR 1.11 (0.97 to 1.28), antenatal bleeding aOR 1.15 (0.92 to 1.44) and very premature birth aOR 1.26 (0.95 to 1.66). Risk of early neonatal mortality and altered heart rate variability is uncertain, very low confidence. Snus using mothers had increased prevalence of caesarean sections, low confidence.

Conclusions

This systematic review reveals that use of smokeless tobacco (snus) during pregnancy may adversely impact the developing child.
Effect of different antibiotic therapies on the reproductive outcomes of fresh embryo transfer for chronic endometritis: A retrospective cohort study
Authors: Liu Jingjing , Wu Sheling , Wang Zhong‐Kai , Liu Xiaoqiang , Liu Wen , Du Yanbo , Yan Lei
Published: December 2022

Objective

To investigate the reproductive outcomes by comparing two kinds of antibiotic schemes for chronic endometritis (CE) in infertile women's fresh embryo transfer (FET) cycles and identify subgroups of patients with CE who need long‐term antibiotics treatment.

Design

A retrospective cohort study.

Setting

University‐based reproductive medical center.

Patient(s)

A total of 492 women with CD138‐positive plasmacytes per 10 high‐power fields (CD138+/10HPF).

Intervention(s)

Hysteroscopy was performed and endometrial biopsy samples were collected in the proliferative phase. Long‐term or short‐term antibiotics were administrated. After antibiotics treatment, patients underwent in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI) and received ET.

Main Outcome Measure(s)

Ongoing pregnancy rate, clinical pregnancy rate, clinical miscarriage rate.

Result (s)

There were no significant differences in pregnancy outcomes between patients with CD138+/10HPF 1–4 (low‐grade CE) who received long‐term antibiotic therapy and short‐term antibiotics groups. Among women with CD138+/10HPF ≥5 (high‐grade CE), live birth rate (48.4% vs. 14.7%, p = .001), clinical pregnancy rate (66.7% vs. 35.3%, p = .002) and ongoing pregnancy rate (59.1% vs. 20.6%, p < .001) in the long‐term arm were significantly higher than that in the short‐term arm. The clinical miscarriage rate (21.0% vs. 58.3%, p = .013) was statistically lower in the long‐term antibiotics group, but no statistical differences were found between the two groups in preterm delivery rate.

Conclusion

Long‐term antibiotics treatment was a sensible choice to improve pregnancy outcomes in women with CD138+/10HPF ≥5 (high‐grade CE). The pregnancy outcomes of women with low‐grade CE only defined by histological diagnosis were not greatly improved after antibiotic therapy. Therefore, we recommended the proper diagnosis criteria were CD138+/10HPF ≥5 pathologically.
Friendly Lobbying under Time Pressure
Authors: Awad Emiel , Minaudier Clement
Published: December 2022

Lobbyists often target legislators who are aligned with them rather than opponents. The choice of whom to lobby affects both what information becomes available to legislators and how much influence special interest groups exert on policies. However, the conditions under which aligned legislators are targeted are not well understood. We investigate how the pressure to conclude policies quickly affects the strategic decision of whom to lobby. We derive conditions on the cost of delaying policies and on the distribution of legislators' preferences for lobbyists to prefer targeting allies. We show that the use of allied intermediaries has important implications for the duration of policymaking and the quality of policies. Counterintuitively, an increase in time pressure can increase the duration of policymaking and a longer duration does not always lead to better informed policies.
Role of deep learning methods in screening for subcutaneous implantable cardioverter defibrillator in heart failure
Authors: ElRefai Mohamed , Abouelasaad Mohamed , Wiles Benedict M. , Dunn Anthony J. , Coniglio Stefano , Zemkoho Alain B. , Morgan John M. , Roberts Paul R.
Published: December 2022

Introduction

S‐ICD eligibility is assessed at pre‐implant screening where surface ECG traces are used as surrogates for S‐ICD vectors. In heart failure (HF) patients undergoing diuresis, electrolytes and fluid shifts can cause changes in R and T waves. Subsequently, T:R ratio, a major predictor of S‐ICD eligibility, can be dynamic.

Methods

This is a prospective study of patients with structurally normal hearts and HF patients undergoing diuresis. All patients were fitted with Holters® to record their S‐ICD vectors. Our deep learning model was used to analyze the T:R ratios across the recordings. Welch two sample t‐test and Mann–Whitney U were used to compare the data between the two groups.

Results

Twenty‐one patients (age 58.43 ± 18.92, 62% male, 14 HF, 7 normal hearts) were enrolled. There was a significant difference in the T:R ratios between both groups. Mean T: R was higher in the HF group (0.18 ± 0.08 vs 0.10 ± 0.05, p < .001). Standard deviation of T: R was also higher in the HF group (0.09 ± 0.05 vs 0.07 ± 0.04, p = .024). There was no difference between leads within the same group.

Conclusions

T:R ratio, a main determinant for S‐ICD eligibility, is higher and has more tendency to fluctuate in HF patients undergoing diuresis. We hypothesize that our novel neural network model could be used to select HF patients eligible for S‐ICD by better characterization of T:R ratio reducing the risk of T‐wave over‐sensing (TWO) and inappropriate shocks. Further work is required to consolidate our findings before applying to clinical practice.
The impact of employee turnover on the financial performance of microfinance institutions: A global evidence
Authors: Mia Md Aslam , Ahmad Noor Hazlina , Halim Hasliza Abdul
Published: December 2022

Microfinance is a preferred development tool in many developing countries around the world; however, the industry has been facing many challenges in recent years, including the attainment of financial sustainability. Therefore, this study is aimed at investigating the effect of employee turnover on the financial performance of microfinance institutions (MFIs). The study utilized unbalanced panel data of 1561 unique MFIs from 2010 to 2018. The data were then analyzed by conventional econometric techniques such as the pooled ordinary least squares, random effects model, fixed effects model, Hausman–Taylor, and the two‐step system generalized method of moments. Considering the linear relationship, it was discovered that employee turnover has a negative effect on the financial performance of MFIs. However, this relationship is dependent on the proxies of financial performance, legal status, location, profit orientation of the MFIs (for subsample analysis), and the technique(s)/model(s) employed in the analysis. Furthermore, the study did not find empirical evidence to support the quadratic relationship between employee turnover and the financial performance of MFIs. The outcome of this study advances important policy implications for concerned stakeholders.