bluuebunny/crossref_metadata_2025 huggingface dataset:
“All of the things to everyone everywhere”: A mixed methods analysis of community perspectives on equitable access to monoclonal antibody treatment for COVID-19
Authors: Kwan Bethany M. , Sobczak Chelsea , Gorman Carol , Roberts Samantha , Owen Vanessa , Wynia Matthew K. , Ginde Adit A. , Pena-Jackson Griselda , Ziegler Owen , DeCamp Lisa Ross
Published: August 2022

Background

Neutralizing monoclonal antibody (mAb) treatment for COVID-19 prevents hospitalization and death but is underused, especially in racial/ethnic minority and rural populations. The study assessed mAbs community awareness and opportunities for improving equitable mAb access.

Methods

A concurrent mixed methods study including surveys and focus groups with adults with high-risk conditions or their proxy decision-makers. Surveys and focus group guides addressed diffusion of innovation theory factors. Descriptive statistics and Fisher’s exact method was used to report and compare survey findings by race and ethnicity. Rapid qualitative methods were used for focus group analysis.

Results

Surveys from 515 individuals (460 English, 54 Spanish, 1 Amharic), and 8 focus groups (6 English, 2 Spanish) with 69 diverse participants, all completed between June 2021 and January 2022. Most survey respondents (75%) had heard little or nothing about mAbs, but 95% would consider getting mAb treatment. Hispanic/Latino and Non-Hispanic People of Color (POC) reported less awareness, greater concern about an intravenous infusion, and less trust in mAb safety and effectiveness than White, Non-Hispanic respondents. Focus group themes included little awareness but high interest in mAb treatment and concerns about cost and access, especially for those facing access barriers such as lacking an established source of care and travel from rural communities. Focus groups revealed preferences for broad-reaching but tailored messaging strategies using multiple media and trusted community leaders.

Conclusions

Despite unfamiliarity with mAb treatment, most respondents were willing to consider receiving mAbs or recommend mAbs to others. While mAb messaging should have broad reach “to everyone everywhere,” racial and geographic disparities in levels of awareness and trust about mAbs underscore the need for tailored messaging to promote equitable access. Care processes should address patient-level mAb barriers, such as transportation, insurance, or primary care access. COVID-19 treatment dissemination strategies should promote health equity.
Functional Contribution of Mesencephalic Locomotor Region Nuclei to Locomotor Recovery After Spinal Cord Injury
Authors: Roussel Marie , Lafrance-Zoubga David , Josset Nicolas , Lemieux Maxime , Bretzner Frederic
Published: August 2022

Spinal cord injury (SCI) results in a disruption of information between the brain and the spinal locomotor circuit. Although the spinal cord contains all the neural circuits to generate locomotion, people with SCI are unable to walk due to the absence of descending commands from the brain. Electrical stimulation of supraspinal locomotor centers, such as the Mesencephalic Locomotor Region (MLR), can promote locomotor recovery in acute and chronic SCI rodent models. Although clinical trials are currently underway in SCI patients, there is still debate about the organization of this supraspinal locomotor center and which anatomical correlate of the MLR should be targeted to promote functional recovery. Combining kinematics, electromyographic recordings, anatomical analysis, and mouse genetics, our study reveals that glutamatergic neurons of the cuneiform nucleus contribute to locomotor recovery by enhancing motor efficacy in flexor and extensor hindlimb muscles, and by increasing locomotor rhythm and speed on a treadmill, over ground, and during swimming in mice with chronic SCI. In contrast, glutamatergic neurons of the pedunculopontine nucleus slow down locomotion. Therefore, our study identifies the cuneiform nucleus and its glutamatergic neurons as a therapeutical target to improve locomotor recovery in patients living with SCI.

One Sentence Summary

Glutamatergic neurons of the mesencephalic locomotor region contribute to spontaneous locomotor recovery following spinal cord injury and selective activation of a discrete glutamatergic subpopulation in this region can further improve functional outcome in chronic spinal cord injury.
On the fitness effects and disease relevance of synonymous mutations
Authors: Shen Xukang , Song Siliang , Li Chuan , Zhang Jianzhi
Published: August 2022

We recently measured the fitness effects of a large number of coding mutations in yeast under four laboratory conditions, finding that most synonymous mutations are strongly deleterious although they are overall significantly less detrimental than nonsynonymous mutations. Kruglyak et al. believe that most nonsynonymous and nearly all synonymous mutations have no detectable fitness effects, so hypothesize that our results largely reflect the fitness effects of CRISPR/Cas9 off-target edits and secondary mutations that occurred in mutant construction. Dhindsa et al. argue that our findings contradict other yeast and human mutagenesis studies, human allele frequency distributions, and disease gene mapping results. We find Kruglyak et al.’s hypothesis unsupported by prior yeast genome editing studies and mutation rate estimates. Furthermore, their hypothesis makes a series of predictions that are falsified by our published and newly collected data. Hence, their hypothesis cannot explain our observations. Dhindsa et al.’s comparisons between synonymous and nonsynonymous mutations in prior mutagenesis studies and in contributions to disease are unfair and human allele frequency distributions can be compatible with our fitness estimates when multiple complicating factors are considered. While our fitness estimates of yeast synonymous mutants overturn the (nearly) neutral assumption of synonymous mutations, they are not inconsistent with various existing data.
Stereoretentive Post-Translational Protein Editing
Authors: Fu Xia-Ping , Yuan Yizhi , Jha Ajay , Levin Nikita , Giltrap Andrew M. , Ren Jack , Mamalis Dimitrios , Mohammed Shabaz , Davis Benjamin G.
Published: August 2022

Chemical post-translational methods now allow convergent side-chain editing of proteins as a form of direct chemical mutagenesis without needing to resort to genetic intervention. Current approaches that allow the creation of constitutionally native side-chains via C–C formation using off-protein carbon-centred C• radicals added to unnatural amino acid radical acceptor SOMOphile ‘tags’ such as dehydroalanine are benign and wide-ranging. However, they also typically create epimeric mixtures of D-/L-residues. Here we describe a light-mediated desulfurative method that, through the creation and reaction of stereoretained on-protein L-alanyl Cβ• radicals, allows Cβ–Hγ, Cβ–Oγ, Cβ–Seγ, Cβ–Bγ and Cβ–Cγ bond formation to flexibly generate site-selectively edited proteins with full retention of native stereochemistry under mild conditions from a natural amino acid. This methodology shows great potential to explore protein side-chain diversity and construct useful bioconjugates.

Table of Contents Image
The FGF/FGFR system in the microglial neuroinflammation with Borrelia burgdorferi: intersectionality with other neurological conditions
Authors: Parthasarathy Geetha , Pattison Melissa B. , Midkiff Cecily C.
Published: August 2022

Background

Lyme neuroborreliosis, caused by the bacterium Borrelia burgdorferi affects both the central and peripheral nervous systems (CNS, PNS). The CNS manifestations, especially at later stages, can mimic/cause many other neurological conditions including psychiatric disorders, dementia, and others, with a likely neuroinflammatory basis. The pathogenic mechanisms associated with Lyme neuroborreliosis, however, are not fully understood.

Methods

In this study, using cultures of primary rhesus microglia, we explored the roles of several fibroblast growth factor receptors (FGFRs) and fibroblast growth factors (FGFs) in neuroinflammation associated with live B. burgdorferi exposure. FGFR specific siRNA and inhibitors, custom antibody arrays, ELISAs, immunofluorescence and microscopy were used to comprehensively analyze the roles of these molecules in microglial neuroinflammation due to B. burgdorferi.

Results

FGFR1- 3 expressions were upregulated in microglia in response to B. burgdorferi. Inhibition of FGFR 1, 2 and 3 signaling using siRNA and three different inhibitors showed that FGFR signaling is proinflammatory in response to the Lyme disease bacterium. FGFR1 activation also contributed to non-viable B. burgdorferi mediated neuroinflammation. Analysis of the B. burgdorferi conditioned microglial medium by a custom antibody array showed that several FGFs are induced by the live bacterium including FGF6, FGF10 and FGF12, which in turn induce IL-6 and/or IL-8 in a dose dependent manner, indicating a proinflammatory nature. To our knowledge, this is also the first-ever described role for FGF6 and FGF12 in CNS neuroinflammation. FGF23 upregulation, in addition, was observed in response to the Lyme disease bacterium. B. burgdorferi exposure also downregulated many FGFs including FGF 5,7, 9, 11,13, 16, 20 and 21. Some of the upregulated FGFs have been implicated in major depressive disorder or dementia development, while the downregulated ones have been demonstrated to have protective roles in epilepsy, Parkinson’s disease, Alzheimer’s disease, spinal cord injury, blood-brain barrier stability, and others.

Conclusions

In this study we show that FGFRs and FGFs are novel mediators of inflammatory pathogenesis in Lyme neuroborreliosis. It is likely that an unresolved, long-term (neuro)-Lyme infection can contribute to the development of other neurologic conditions in susceptible individuals either by augmenting pathogenic FGFs or by suppressing ameliorative FGFs or both.
Inferring single-cell transcriptomic dynamics with structured latent gene expression dynamics
Authors: Farrell Spencer , Mani Madhav , Goyal Sidhartha
Published: August 2022

Gene expression dynamics provide directional information for trajectory inference from single-cell RNA-sequencing data. Traditional approaches compute local RNA velocity using strict assumptions about the equations describing transcription and splicing of RNA. Not surprisingly, these approaches fail where these assumptions are violated, such as in multiple lineages with distinct gene dynamics or time-dependent kinetic rates of transcription and splicing. In this work we present “LatentVelo”, a novel approach to compute a low-dimensional representation of gene dynamics with deep learning. Our approach embeds cells into a latent space with a variational auto-encoder, and describes differentiation dynamics on this latent space with neural ordinary differential equations. These more general dynamics enable accurate trajectory inference, and the latent space approach enables the generation of a latent “dynamics-based” embedding of cell states. To model multiple distinct lineages, LatentVelo infers a latent regulatory state that controls the dynamics of an individual cell. With these lineage-specific dynamics LatentVelo can predict latent trajectories, describing global inferred developmental path for individual cells, rather than just outputting local RNA velocity vectors. The dynamics-based embedding also enables concurrent batch correction of cell states and RNA velocity, outperforming comparable auto-encoder based batch correction methods that do not consider gene expression dynamics. Finally, the flexible structure of LatentVelo enables additional of new regulatory constraints required to integrate multiomic data. LatentVelo is available athttps://github.com/Spencerfar/LatentVelo.
Balance between maternal antiviral response and placental transfer of protection in gestational SARS-CoV-2 infection
Authors: Gonçalves Juliana , Melro Magda , Alenquer Marta , Araújo Catarina , Castro-Neves Júlia , Charepe Nádia , Serrano Fátima , Pontinha Carlos , Amorim Maria João , Soares Helena
Published: August 2022

Maternal immune responses during pregnancy protect the growing fetus by clearing infection, preventing its vertical transmission, and through transplacental transfer of protective immune mediators to the fetus. How maternal immune response balances SARS-CoV-2 antiviral responses with transplacental transfer of protection to the fetus remains unclear. Our study shows that upon SARS-CoV-2 maternal infection, neutralizing antibodies (NAbs) are infrequently detected in cord blood. We uncovered that this is due to impaired IgG-NAbs placental transfer in symptomatic infection and to the predominance of maternal SARS-CoV-2 NAbs of the IgA and IgM isotypes, which are prevented from crossing the placenta. Crucially, the decision between favoring maternal antiviral response or transplacental transfer of immune protection to the fetus appears to hinge on the balance between IL-6 and IL-10 induced by SARS-CoV-2 infection, decreasing or increasing transplacental transfer of IgG-NAbs, respectively. In addition, IL-10 inversely correlates with maternal NK cell frequency. Finally, we found that ongoing infection favored perinatal transfer of maternal NK cells, highlighting a maternal sponsored mechanism to protect the newborn from horizontal transmission of infection. Our data point to an evolutionary trade-off which at once optimizes maternal viral clearance and vertical transfer of immune protection during the more susceptible perinatal period.

Brief Summary

In SARS-CoV-2 maternal infection, the balance between maternal antiviral response and transplacental transfer of cellular and humoral (NAb) protection hinges on maternal IL-6 and IL-10.
DNA methylation in clonal Duckweed lineages (Lemna minorL.) reflects current and historical environmental exposures
Authors: Van Antro Morgane , Prelovsek Stella , Ivanovic Slavica , Gawehns Fleur , Wagemaker Niels C.A.M. , Mysara Mohamed , Horemans Nele , Vergeer Philippine , Verhoeven Koen J.F.
Published: August 2022

While some DNA methylation variants are transgenerationally stable in plants, DNA methylation modifications that are specifically induced by environmental exposure are typically transient and subject to resetting in germ lines, limiting the potential for transgenerational epigenetics stress memory. Asexual reproduction circumvents germlines, and may be more conducive to long-term memory and inheritance of epigenetic marks. This, however, has been poorly explored. Taking advantage of the rapid clonal reproduction of the common duckweedLemna minor, we tested the hypothesis that a long-term, transgenerational stress memory from exposure to high temperature can be detected in DNA methylation profiles. Using a reduced representation bisulfite sequencing approach (epiGBS), we show that high temperature stress induces DNA hypermethylation at many cytosines in CG and CHG contexts but not in CHH. In addition, a subset of the temperature responsive CHG cytosines, showed differential DNA methylation between in lineages exposed to 30°C and 24°C, 3-12 clonal generations after subsequent culturing in a common environment, demonstrating a memory effect of stress that persists over many clonal generations and that is reflected in DNA methylation. Structural annotation revealed that this memory effect in CHG methylation was enriched in TEs. We argue that the observed epigenetic stress memory is likely caused by stable transgenerational persistence of high temperature-induced DNA methylation variants across multiple clonal generations. To the extent that such epigenetic memory has functional consequences for gene expression and phenotypes, this result suggests potential for long-term modulation of stress responses in asexual plants and vegetatively propagated crops.
The soft X-ray monochromator at the SASE3 beamline of the European XFEL: from design to operation
Authors: Gerasimova N. , La Civita D. , Samoylova L. , Vannoni M. , Villanueva R. , Hickin D. , Carley R. , Gort R. , Van Kuiken B. E. , Miedema P. , Le Guyarder L. , Mercadier L. , Mercurio G. , Schlappa J. , Teichman M. , Yaroslavtsev A. , Sinn H. , Scherz A.
Published: August 2022

The SASE3 soft X-ray beamline at the European XFEL has been designed and built to provide experiments with a pink or monochromatic beam in the photon energy range 250–3000 eV. Here, the focus is monochromatic operation of the SASE3 beamline, and the design and performance of the SASE3 grating monochromator are reported. The unique capability of a free-electron laser source to produce short femtosecond pulses of a high degree of coherence challenges the monochromator design by demanding control of both photon energy and temporal resolution. The aim to transport close to transform-limited pulses poses very high demands on the optics quality, in particular on the grating. The current realization of the SASE3 monochromator is discussed in comparison with optimal design performance. At present, the monochromator operates with two gratings: the low-resolution grating is optimized for time-resolved experiments and allows for moderate resolving power of about 2000–5000 along with pulse stretching of a few to a few tens of femtoseconds RMS, and the high-resolution grating reaches a resolving power of 10 000 at the cost of larger pulse stretching.
How social self-efficacy and emotional self-efficacy moderate the relationship between occupational stress and knowledge hiding in Brazilian software industry
Authors: Jneid Cherine
Published: August 2022

Purpose

Software industry, one of the most knowledge-intensive industries, in Brazil has increased opportunities of evolution. Its competitive advantage relies on the efficiency of the organizational knowledge management, but the knowledge hiding, its antecedents and moderators are still understudied. This study seeks to identify a new antecedent to knowledge hiding, such the occupational stress.

Design/methodology/approach

The author focused on the moderating effect of social self-efficacy and emotional self-efficacy in the relationship between occupational stress and knowledge hiding in software industry in Brazil. The author collected data from 189 software industry Brazilian employees in 30 firms using a time-lagged research design.

Findings

This study demonstrated that employees with high levels of social self-efficacy (SSE) and emotional self-efficacy (ESE) or both have more tendency to engage on knowledge hiding behavior comparing to their colleagues with low SSE and ESE. This study showed that SSE and ESE related positively to rationalized hiding, evasive hiding and playing dumb.

Originality/value

The author’s main contribution relies on the finding related to the joint role of social self-efficacy and emotional self-efficacy on engaging employees under occupational stress conditions in knowledge hiding behaviors.
Towards a better understanding of the concept of revenge against banks
Authors: Elhajjar Samer
Published: August 2022

Purpose

The purpose of this research is to investigate the concept of revenge against banks.

Design/methodology/approach

Structural equation modeling was used to test hypotheses based on collected survey data. A total of 625 questionnaires were collected from Lebanese customers.

Findings

Research findings identify multiple antecedents to consumers' desire for revenge against banks by encapsulating the cognitive, emotional, social, and personal patterns that influence the desire for revenge. The author found that the desire for revenge fuels direct behavioral reactions towards bank.

Practical implications

Consumer revenge remains underdeveloped in marketing research. This study provides managerial recommendations to assist bank response strategies in managing consumer revenge behaviors.

Originality/value

This study is one of very few that explores the concept of revenge against financial institutions, specifically by connecting the literature to the discovery of cognitive, affective, and social factors. This paper contributes to the existing body of knowledge by highlighting the role of personality traits in consumer revenge. This study’s research implications are built on unique findings in a developing country, while most extensive studies that boost negative public attitudes toward the banking industry are established in developed countries.
Compassion and altruism in organizations: a path for firm survival
Authors: Barghouti Zina , Guinot Jacob , Chiva Ricardo
Published: August 2022

Purpose

The authors draw on this approach to explore the consequences of compassion and altruism in the workplace for firm performance, using organizational resilience as a mediating variable.

Design/methodology/approach

In recent years, a paradigm shift has been proposed in the organizational sciences that includes a change from self-centeredness to interconnectedness. This emergent management paradigm considers that employees are not only motivated by self-interest but also by other-centered values, such as altruism and compassion for others. This alternative proposal suggests the need for a more humanistic perspective for management. To carry out the research, the authors applied a structural equation model to a sample of highly innovative companies from different sectors.

Findings

The results confirm that compassion at work leads to a climate based on altruism, which indirectly increases firm performance by means of organizational resilience. This study contributes to the organizational literature by revealing some benefits of promoting altruism and compassion in organizations.

Originality/value

This study therefore provides a detailed analysis of the consequences of altruism and compassion in organizations and reveals some organizational conditions that can drive firm performance. Moreover, this study is the first to suggest and empirically validate that a work climate based on altruism enhances organizational resilience. In turn, organizational resilience enables the firm to take appropriate actions to convert unexpected and adverse situations that potentially threaten its survival into sources of opportunity and growth.
How and when do exporters benefit from an international adaptation strategy? The moderating effect of formal and informal institutional distance
Authors: Gao Jie , Wang Tao , Jia Yu , Wang Cheng Lu
Published: August 2022

Purpose

Drawing on institutional theory, this study seeks to advance the understanding of how the indirect effect of exporters' adoption of an international adaptation strategy on export performance via enhanced legitimacy is differently moderated by formal and informal institutional distances from the host country market.

Design/methodology/approach

Survey data were collected from a sample of 251 exporters in China and analyzed with a multiple regression model to test the hypotheses.

Findings

Exporters' use of an international adaptation strategy affects their perceived legitimacy, which in turn influences their export performance. Moreover, formal institutional distance strengthens the indirect effect of an international adaptation strategy on export performance via legitimacy, whereas informal institutional distance weakens this indirect effect.

Originality/value

The study contributes to the knowledge of how and when adoption of an international adaptation strategy by exporters benefits export performance from an institutional perspective.
Adaptive sliding mode control for tunnel boring machine cutterhead telescopic system with uncertainties
Authors: Zhang Hangjun , Fang Jinhui , Wei Jianhua , Yu Huan , Zhang Qiang
Published: August 2022

Purpose

This paper aims to present an adaptive sliding mode control (ASMC) for tunnel boring machine cutterhead telescopic system with uncertainties to achieve a high-precision trajectory in complex strata. This method could be applied to solve the problems caused by linear and nonlinear model uncertainties.

Design/methodology/approach

First, an integral-type sliding surface is defined to reduce the static tracking error. Second, a projection type adaptation law is designed to approximate the linear and nonlinear redefined parameters of the electrohydraulic system. Third, a nonlinear robust term with a continuous approximation function is presented for handling load force uncertainty and reducing sliding mode chattering. Moreover, Lyapunov theory is applied to guarantee the stability of the closed-loop system. Finally, the effectiveness of the proposed controller is proved by comparative experiments on a scaled test rig.

Findings

The linear and nonlinear model uncertainties lead to large variations in the dynamics of the mechanism and the tracking error. To achieve precise position tracking, an adaptation law was integrated into the sliding mode control which compensated for model uncertainties. Besides, the inherent sliding mode chattering was reduced by a continuous approximation function, while load force uncertainty was solved by a nonlinear robust feedback. Therefore, a novel ASMC for tunnel boring machine cutterhead telescopic system with uncertainties can improve its tracking precision and reduce the sliding mode chattering.

Originality/value

To the best of the authors’ knowledge, the ASMC is proposed for the first time to control the tunnel boring machine cutterhead telescopic system with uncertainties. The presented control is effective not only in control accuracy but also in parameter uncertainty.
Impact of project governance on project success, with mediating role of organizational support and project team cohesion
Authors: Waseem Muhammad , Iqbal Shahid , Khan Khalid
Published: August 2022

Purpose

The purpose of this study is to determine how project governance influences project success. According to the authors, such an effect is mediated by organizational support and project team cohesion. The direct and indirect effects of organizational support and project team cohesion provided helpful information. The authors’ objective is to contribute to the project management knowledge of how project team cohesion plays a significant role in project success.

Design/methodology/approach

Data were collected from 350 employees working in Pakistan’s oil and gas industry. Four prime oil and gas exploration companies were selected as samples based on their contribution to the revenue. SPSS v23 and AMOS v23 were used for constructing structural equation modeling and path analysis to examine the direct and indirect effects.

Findings

The results revealed that project governance is positively related to project success. Furthermore, organizational support and project team cohesion mediated the relationship between project governance and project success.

Originality/value

Team cohesion has been primarily a topic of interest in sports psychology literature, education and medical sciences. There is an expressed need to investigate team cohesion issues in the broad domain of organizational development, specifically the project management literature. This study contributed by discussing team cohesion in the project context. Second, project governance was investigated using the conservation of resources theory. The lens of intellectual capital was applied to examine intangible resources of project governance like rules, regulations and directives for project success.
Attitudes toward peers, supervisors, and citizens: a comparison of Chinese and Taiwanese police officers
Authors: Wu Yuning , Sun Ivan , Lo Tzu-Ying , Liu Jianhong
Published: August 2022

Purpose

This paper comparatively assesses the connections between individual demographic traits, occupational characteristics, and organizational factors and officers' attitudes toward important groups in China and Taiwan.

Design/methodology/approach

Survey data used in this study were collected from 722 police officers from mainland China and 531 officers from Taiwan. Multivariate regression analyses were conducted to assess the correlates of police attitudes toward peers, supervisors, and citizens.

Findings

The Chinese and Taiwanese officers do not differ in their trust in peers, but the Chinese officers hold significantly more positive views on the trustworthiness of supervisors and citizens compared to the Taiwanese officers. Supervisor justice and organizational identification are significant predictors of officers' attitudes toward all three groups in both countries.

Research limitations/implications

A major limitation revolves around the inability to test and explain exactly why findings from the two groups vary in their ways. Future research should include specific social, political, and cultural predictors.

Originality/value

This study represents one of the few studies that compare police attitudes toward important groups of peers, supervisors, and citizens across nations/cultures.
English Version of Clinical Practice Guidelines for the Management of Atopic Dermatitis 2021
Authors: Saeki Hidehisa , Ohya Yukihiro , Furuta Junichi , Arakawa Hirokazu , Ichiyama Susumu , Katsunuma Toshio , Katoh Norito , Tanaka Akio , Tsunemi Yuichiro , Nakahara Takeshi , Nagao Mizuho , Narita Masami , Hide Michihiro , Fujisawa Takao , Futamura Masaki , Masuda Koji , Matsubara Tomoyo , Murota Hiroyuki , Yamamoto‐Hanada Kiwako
Published: August 2022

This is the English version of the Clinical Practice Guidelines for the Management of Atopic Dermatitis 2021. Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. In Japan, from the perspective of evidence‐based medicine, the current strategies for the treatment of AD consist of three primary measures: (i) use of topical corticosteroids, tacrolimus ointment, and delgocitinib ointment as the main treatment of the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling, and advice about daily life. In the present revised guidelines, descriptions of three new drugs, namely, dupilumab, delgocitinib, and baricitinib, have been added. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity‐related patient outcomes with respect to several important points requiring decision‐making in clinical practice.
Impact of COVID‐19 pandemic on emergency department patient volume and flow: Two countries, two hospitals
Authors: Del Mar Peter , Kim Min Joung , Brown Nathan J , Park Joon Min , Chu Kevin , Burke John
Published: August 2022

Objectives

COVID‐19 greatly disrupted the provision of emergency care across the globe. ED service delivery was urgently redesigned as human and material resources were mobilised, and patients with respiratory symptoms were isolated. This study aimed to compare ED patient volume and flow metrics before and during the COVID‐19 pandemic.

Methods

An observational study was conducted in two large urban EDs in Brisbane, Australia and Seoul, Republic of Korea. Patient volume and flow were quantified using ED presentation numbers and service times, respectively. Daily case numbers, waiting, treatment and admission delay times were compared between 2019 and 2020/2021 using time series plots. Outcomes were further classified by triage category and age group. Trends were examined alongside a timeline of health service and government policies.

Results

There were reductions in daily presentations for the least urgent triage categories during the early phase of the pandemic. The caseloads for the most urgent triage categories were unaffected. The trends were similar in both EDs. A reduction in waiting and admission delay times but not treatment times coincided with reduced presentations in Brisbane. This pattern gradually reversed as presentations returned to baseline. In Seoul, admission delay times returned to pre‐pandemic levels despite a persistent reduction in presentation numbers.

Conclusions

Total daily presentations varied considerably according to government mandated social restrictions and testing requirements in both EDs. The reductions in waiting and admission delay times corresponded with improvements in hospital capacity.
Non‐ribosomal peptide biosynthetic potential of the nematode symbiont Photorhabdus
Authors: Du Ao‐Qi , Ying Ti‐Ti , Zhou Zhen‐Yi , Yu Wen‐Chao , Hu Gang‐Ao , Luo Xian , Ma Man‐Jing , Yu Yan‐Lei , Wang Hong , Wei Bin
Published: August 2022

Photorhabdus, the symbiotic bacteria of Heterorhabditis nematodes, has been reported to possess many non‐ribosomal peptide synthetase (NRPS) biosynthesis gene clusters (BGCs). To provide an in‐depth assessment of the non‐ribosomal peptide biosynthetic potential of Photorhabdus, we compared the distribution of BGCs in 81 Photorhabdus strains, confirming the predominant presence (44.80%) of NRPS BGCs in Photorhabdus. All 990 NRPS BGCs were clustered into 275 gene cluster families (GCFs) and only 13 GCFs could be annotated with known BGCs, suggesting their great diversity and novelty. These NRPS BGCs encoded 351 novel peptides containing more than four amino acids, and 173 of them showed high sequence similarity to known BGCs encoding bioactive peptides, implying the promising potential of Photorhabdus to produce valuable peptides. Sequence similarity networking of adenylation (A‐) domains suggested that the substrate specificity of A‐domains was not directly correlated with the sequence similarity. The molecular similarity network of predicted metabolite scaffolds of NRPS BGCs and reported peptides from Photorhabdus and a relevant database demonstrated that the non‐ribosomal peptide biosynthetic potential of Photorhabdus was largely untapped and revealed the core peptides deserving intensive studies. Our present study provides valuable information for the targeted discovery of novel non‐ribosomal peptides from Photorhabdus.
Serum C‐reactive protein adds predictive information for post‐stroke delirium: The PROPOLIS study
Authors: Klimiec‐Moskal Elzbieta , Slowik Agnieszka , Dziedzic Tomasz
Published: August 2022

Objective

Delirium is common and serious complication after stroke. Accurate prediction of delirium is important for prevention and monitoring of high‐risk patients. Our study aimed to determine if addition of C‐reactive protein (CRP) to a model based on easy‐to‐access clinical predictors improves accuracy of delirium prediction in acute stroke patients.

Methods

We analyzed data of patients participating in the Prospective Observational Polish Study on post‐stroke delirium. We included patients admitted within 24 h after stroke or transient ischemic attack (TIA) in whom serum CRP was measured on admission. We examined core features of delirium during first 7 days of hospitalization. We assessed if addition of CRP to two clinical models improved metrics of discrimination and reclassification. Model A included age and stroke severity and Model B included stroke severity, atrial fibrillation, diabetes mellitus, pre‐stroke dependency, and hemorrhagic stroke.

Results

We included 459 patients. We diagnosed delirium in 29.2% of them. Patients who developed delirium had higher CRP level than those without delirium (median: 13.2 vs. 4.4 mg/L, p < 0.001). CRP >7.09 mg/L was associated with an increased risk of delirium (adjusted OR: 2.98, 95%CI: 1.71–5.19, p < 0.001). After adding CRP to clinical models, an area under receiver operator curve increased from 0.77 to 0.80 (p = 0.038) for Model A and from 0.81 to 0.84 (p = 0.016) for Model B. There was also improvement in reclassification.

Conclusions

Addition of CRP to clinical predictors moderately improved prediction of post‐stroke delirium. CRP could be considered as a potential biomarker to stratify risk of delirium after stroke.
Characterization and functional analysis of lncRNA2690 in regulating the growth cycle of the hair follicle in rabbits
Authors: Bao Zhiyuan , Zhai Pin , Yao Fan , Ren Yuyao , Zhao Bohao , Chen Yang , Wu Xinsheng
Published: August 2022

Hair follicles (HFs) achieve hair growth and renewal by periodic regeneration. Therefore, exploring the key factors affecting hair growth in rabbits is of great significance for precisely breeding Angora rabbits and improving the competitiveness of the rabbit industry. Based on the results of our previous studies, lncRNA2690 was differentially expressed in the HF cycle using lncRNA‐Seq, and the full‐length sequence was annotated by bioinformatics analysis. The lncRNA2690 is 363 nt long and is found on chromosome 14 from 163 321 514 to 163 321 872. The lncRNA2690 was predicted to not have the coding ability through open reading frame and CPC2, and the nuclear–cytoplasmic separation experiment showed the lncRNA2690 to be highly expressed in the nucleus (p < 0.01). The expression pattern of lncRNA2690 was further analyzed in the different HF development stages of Angora rabbits using quantitative real‐time PCR. The results showed that lncRNA2690 was periodically expressed in HF development, and the expression level was found to be high in the HF resting phases. The overexpression and knockdown of lncRNA2690 were found to significantly upregulate and downregulate the expression of the genes WNT2, CCND1, BMP2, LEF1, and SIAH1 in the rabbit dermal papilla cells (p < 0.01), promoting cell apoptosis and inhibiting cell proliferation (p < 0.01). This indicated that lncRNA2690 negatively regulates the periodic regeneration of the HFs in rabbits. These results provide a basis for the further study of lncRNA2690 in the HF growth cycle of Angora rabbits.
Comparative proteome profiling of seminal components reveal impaired immune cell signalling as paternal contributors in recurrent pregnancy loss patients
Authors: Jena Soumya Ranjan , Nayak Jasmine , Kumar Sugandh , Kar Sujata , Samanta Luna
Published: August 2022

Problem

Recurrent pregnancy loss (RPL) is usually evaluated from a women's perspective, however, recent evidence implies involvement of male factors as paternally expressed genes predominate placenta. During fertilization, prior to implantation the immune system purposefully produces early pregnancy factors with potent immunomodulatory properties for adaptation to antigenically dissimilar embryo. Therefore, it is hypothesized that paternal immunological factors play a role in RPL.

Method of study

Comparative proteome profiling (label free liquid chromatography mass spectroscopy: LC‐MS/MS) of the seminal extracellular vesicles (SEVs), extracellular vesicle free seminal plasma (EVF‐SP) and spermatozoa was carried out in semen of RPL patients (n = 21) and fertile donors (n = 21). This was followed by pathway and protein‐protein interaction analysis, and validation of key proteins' expression (western blot).

Results

A total of 68, 28 and 49 differentially expressed proteins in SEVs, EVF‐SP and spermatozoa of RPL patients, respectively, were found to be involved in inflammatory response, immune cell signalling and apoptosis. In SEVs, underexpressed GDF‐15 and overexpressed C3 imply distorted maternal immune response to paternal antigens leading to impaired decidualization. Dysregulated TGFβ signalling in EVF‐SP surmises defective modulation of inflammatory response and induction of immune tolerance to seminal antigens in the female reproductive tract through generation of regulatory T cells. Retained histone variants in spermatozoa construe defective expression of early paternal genes, while underexpressed PTN may inflict defective angiogenesis resulting in expulsion of decidua.

Conclusions

Impaired modulation of immune response and improper placental development due to altered cytokine levels in seminal components may be the contributing paternal factors in RPL.
Diabetes mellitus and risk of open‐angle glaucoma—A population‐based follow‐up study
Authors: Virtanen Aapo , Haukka Jari , Loukovaara Sirpa , Harju Mika
Published: August 2022

Purpose

The aim of this study was to investigate the association of diabetes mellitus (DM) and risk of open‐angle glaucoma (OAG).

Methods

This population‐based historic cohort consisted of individuals at age ≥ 40 years with DM treatment initiated 2001–2010 and a reference population matched by age, gender and hospital district. Incidence of OAG was compared between individuals with DM and their matched non‐diabetic reference pairs. New glaucoma cases were identified from medication reimbursement certificates and hospital billing records. Incidence rate ratios (IRR) were analysed with Poisson regression models adjusted for age, sex, hospital district, socioeconomic status, systemic medications and chronic diseases. We analysed the sensitivity of the results with adapted input variables and performed a competing events analysis.

Results

Of the 244 100 study subjects meeting inclusion criteria, 2721 (1.1%) developed OAG. Follow‐up spanned from 2001 to 2017. DM was associated with a modestly reduced incidence of OAG when adjusted for confounding factors (IRR 0.92, CI 0.85–0.99).

Conclusions

In our longitudinal population‐based study, we found a modest decrease in the risk of OAG for individuals with DM.
More than ‘more than ever’: Revisiting a work design and sociotechnical perspective on digital technologies
Authors: Parker Sharon K. , Grote Gudela
Published: August 2022

We respond to commentaries on our 2020 article ‘Automation, algorithms, and beyond: Why work design matters more than ever in a digital world’ and report on research on the topic since that publication. A top‐down work design perspective on digital technologies appears even more important than ever yet still neglected, as suggested by recent studies. The opportunities and challenges of new technologies have been addressed somewhat more successfully through bottom‐up work design in the form of job crafting. The specific topic of virtual working has also attracted significant research attention. Nevertheless, we continue to advocate more scholarly and practical attention to the following: how to proactively redesign work when introducing new technologies; how work design issues can be built into the design and procurement of work technologies; the need to identify and understand both the organizationally oriented strategies and macro‐level change needed for successful sociotechnical application; and how to upskill employees, managers, unions and other stakeholders, in work design and related topics. There is also more scope for consideration of the role of individual differences. Finally, we call for interdisciplinary research that involves, for example, the designers of technology, and we advocate the importance of intervention studies.
Editorial: potassium‐competitive acid blockers—is there a role for more complete acid suppression?
Authors: DeVault Kenneth R.
Published: August 2022

LINKED CONTENT

This article is linked to Chen et al papers. To view these articles, visit https://doi.org/10.1111/apt.16959 and https://doi.org/10.1111/apt.17176
Editorial: slow progress to optimising H. pylori eradication treatment with antisecretory drugs—authorsʼ reply
Authors: Ang Daphne , Koo Seok‐Hwee
Published: August 2022

LINKED CONTENT

This article is linked to Ang et al papers. To view these articles, visit https://doi.org/10.1111/apt.17070 and https://doi.org/10.1111/apt.17142
Editorial: switching to tenofovir alafenamide monotherapy is effective and safe for other nucleos(t)ide analogues‐treated patients with chronic hepatitis B ‐ author's reply
Authors: Ogawa Eiichi
Published: August 2022

LINKED CONTENT

This article is linked to Ogawa et al papers. To view these articles, visit https://doi.org/10.1111/apt.17107 and https://doi.org/10.1111/apt.17122
Editorial: investigating the association between sweetened beverages and risk of inflammatory bowel disease
Authors: Lopes Emily Walsh , Khalili Hamed
Published: August 2022

LINKED CONTENT

This article is linked to Fu et al papers. To view these articles, visit https://doi.org/10.1111/apt.17149 and https://doi.org/10.1111/apt.17187
Terlipressin use and respiratory failure in patients with hepatorenal syndrome type 1 and severe acute‐on‐chronic liver failure
Authors: Wong Florence , Pappas Stephen Chris , Reddy K. Rajender , Vargas Hugo , Curry Michael P. , Sanyal Arun , Jamil Khurram
Published: August 2022

Background

Previous studies suggested increased mortality in patients with hepatorenal syndrome type 1 (HRS1) and advanced acute‐on‐chronic liver failure (ACLF).

Aim

To assess mortality and respiratory failure (RF) in patients with HRS1 and ACLF treated with terlipressin.

Methods

In the CONFIRM study, we randomised 299 patients with HRS1 2:1 to terlipressin or placebo, both with albumin. At enrolment, all patients were assessed for organ failure (OF) using a validated ACLF grading system. Post hoc analyses assessed the effects of terlipressin vs. placebo on the incidence of RF and 90‐day mortality.

Results

The incidence of RF with terlipressin (n = 200) was 9.4% in patients with grades 1–2 ACLF, and 30% with grade 3 ACLF (p = 0.0002); no such difference was observed in placebo‐treated patients (n = 99) (6.2% grades 1–2 vs. 0% grade 3 ACLF, p > 0.05). RF incidence between terlipressin and placebo in patients with grade 3 ACLF was significant (p = 0.01). Baseline predictors of RF with terlipressin were INR (p = 0.011), mean arterial pressure (p = 0.037), and SpO2 (p = 0.014). Prior albumin as a continuous variable was not a predictor of RF. 90‐day survival between terlipressin and placebo arms was similar for grades 1–2 ACLF (55.5% and 56.6%, respectively), but lower for grade 3 ACLF (27.55% vs. 50.0%) (p = 0.122), mainly related to RF.

Conclusion

Terlipressin should be used with caution in patients with HRS1 and grade 3 ACLF. Patients with hypoxaemia are at increased risk of RF and mortality.
An exploratory qualitative analysis of rape myths in India
Authors: Damania Mrunali H. , Singh Ram Manohar
Published: August 2022

Rape myths are stereotypical beliefs that excuse the rapist and hold the victim responsible for rape, leading to secondary victimization. This study attempts to grasp the nature of rape myths in the Indian context and compares them with rape myths that appear in the literature. Detailed semi‐structured interviews were conducted with members of the general public (shopkeepers, clerks, students, counselors, peons, and guards) and legal actors (police personnel and lawyers). Results are discussed regarding the rejection of or support for rape myths and additional rape myths. Interestingly, we found that Indians are not supportive of rape myths that excuse rapists when they are influenced by alcohol. In support of previously researched rape myths, we found that Indians overestimated false accusations and blamed revealing clothes, women's drinking, and going out at night. We also found additional rape myths prevalent in India that are unique but not necessarily restricted to the Indian context. These include 'western' clothes, lack of parental control, disregard for traditional norms, provoking anger in males, and going out for leisure. Our findings suggest that the nature and intensity of rape myths vary according to culture. Assessment tools and educational interventions need to be tailored according to these variations.