bluuebunny/crossref_metadata_2025 huggingface dataset:
Atypical influence of biomechanical knowledge in Complex Regional Pain Syndrome-Towards a different perspective on body representation
Authors: Filbrich L. , Verfaille C. , Vannuscorps G. , Berquin A. , Barbier O. , Libouton X. , Fraselle V. , Mouraux D. , Legrain V.
Published: October 2021

Part of the multifaceted pathophysiology of Complex Regional Pain syndrome (CRPS) has been ascribed to a lateralized maladaptive neuroplasticity in sensorimotor cortices, a finding that has been corroborated by behavioral studies indicating that CRPS patients indeed present difficulties in mentally representing their painful limb. Hand laterality judgment tasks (HLT) are widely used to measure such difficulties, with the laterality of hand stimuli corresponding to the affected hand judged more slowly than the one of hand stimuli corresponding to the unaffected hand. Importantly, the HLT is also regularly used in the rehabilitation of CRPS and other chronic pain disorders, with the aim to activate motor imagery and, consequently, restoring the cortical representation of the limb. The potential of these tasks to elicit motor imagery is thus critical to their use in therapy. Yet, the influence of the biomechanical constraints (BMC) on HLT reaction time, supposed to reflect the activation of motor imagery, is rarely verified. In the present study we investigated the influence of the BMC on the perception of hand postures and movements. The results of a first experiment, in which a HLT was used, showed that CRPS patients were significantly slower than controls in judging hand stimuli, whether or not the depicted hand corresponded to their affected hand, but that their performance did not differ from controls when they judged non-body stimuli. Results regarding reaction time patterns reflecting the BMC were inconclusive in CRPS and controls, questioning the validity of the task in activating motor imagery processes. In a second experiment we therefore directly investigated the influence of implicit knowledge of upper-limb BMC on perceptual judgments of hand movements with the apparent body movement perception task. Participants judge the perceived path of movement between two depicted hand positions, with only one of the two proposed paths that is biomechanically plausible. While the controls chose the biomechanically plausible path most of the time, CRPS patients did not, indicating that the perception and/or use of the BMC seems to be disturbed in CRPS. These findings show a non-lateralized body representation impairment in CRPS, which might be related to difficulties in using correct knowledge of the body’s biomechanics. Most importantly however, our results, in agreement with previous studies, indicate that it seems highly challenging to measure motor imagery and the indexes of BMC with the classical HLT task, which has important implications for the rehabilitation of chronic pain with these tasks.
The association of infectious mononucleosis and breast cancer in The Health of Women (HOW) Study®
Authors: Heng Yujing J. , Love Susan , DeHart Jessica Clague , Fingeroth Joyce D. , Wulf Gerburg M.
Published: October 2021

Background

The link between Epstein-Barr Virus (EBV) and breast cancer (BC) remains unclear. Infectious mononucleosis (IM) is a clinical manifestation of delayed onset of EBV infection in early adulthood. We utilized the Health of Women (HOW) Study® to understand the association between IM and BC risk.

Subjects and methods

The HOW Study® was a web-based survey of BC risk factors with >40,000 participants who answered seven modules between 2012 and 2015; 3,654 women had IM between the ages of 10 and 22 years (16.8%) and 17,026 never developed IM (78.5%). Of these 20,680 women, 1,997 (9.7%) had Stages I-III BC and 13,515 (65.4%) were cancer-free. Multivariable binary logistic regression ascertained the association between IM and BC risk by controlling for ethnicity, family history, age at menarche, oral contraceptive use, tobacco use, birthplace, parity, age at first birth, body mass index, and breast biopsy. Secondary analyses stratified cancer cases into those who had BC at <50 or ≥50 years old and by estrogen receptor (ER) subtype.

Results

Participants were mostly white, middle-aged women born in the United States or Canada. Women who had IM were less likely to develop BC than those who did not develop IM (adjusted odds ratio (OR)=0.83, 95% confidence interval (CI) 0.71-0.96). Findings were similar when stratifying women into <50 or ≥50 years old at BC diagnosis (<50 years old, adjusted OR=0.82, 95% CI 0.67-0.998; ≥50 years old, adjusted OR=0.83, 95% CI 0.69-1.00). Women who had IM were less likely to develop ER positive BC (adjusted OR=0.84, 95% CI 0.71-0.997); there was no association between IM and ER negative BC (adjusted OR=0.88, 95% CI 0.65-1.16).

Conclusion

In the HOW Study®, women diagnosed with IM between the ages of 10 and 22 had lower breast cancer risk compared to women who never developed IM.
Tuning DO:DM ratios modulates MHC class II immunopeptidomes
Authors: Olsson Niclas , Jiang Wei , Adler Lital N. , Mellins Elizabeth D. , Elias Joshua E.
Published: October 2021

Major histocompatibility complex class II (MHC-II) antigen presentation underlies a wide range of immune responses in health and disease. However, how MHC-II antigen presentation is regulated by the peptide-loading catalyst HLA-DM (DM), its associated modulator, HLA-DO (DO), is incompletely understood. This is due largely to technical limitations: model antigen presenting cell (APC) systems that express these MHC-II peptidome regulators at physiologically variable levels have not been described. Likewise, computational prediction tools that account for DO and DM activities are not presently available. To address these gaps, we created a panel of single MHC-II allele, HLA-DR4-expressing APC lines that cover a wide range of DO:DM ratio states. Using a combined immunopeptidomic and proteomic discovery strategy, we measured the effects DO:DM ratios have on peptide presentation by surveying over 10,000 unique DR4-presented peptides. The resulting data provide insight into peptide characteristics that influence their presentation with increasing DO:DM ratios. These include DM-sensitivity, peptide abundance, binding affinity and motif, peptide length and register positioning on the source protein. These findings have implications for designing improved HLA-II prediction algorithms and research strategies for dissecting the variety of functions that different APCs serve in the body.

IN BRIEF

Peptides presented by MHC-II are critical to adaptive immune function. The non-canonical MHC molecules HLA-DM and HLA-DO cooperatively regulate MHC-II function, but how varied DO-to-DM ratios across different APCs and cellular contexts might influence their immunopeptide repertoires is unclear. We address this by measuring cell lines expressing these two proteins spanning a range of relative abundances. We found that peptides could be categorized according to how robustly they were presented at different DO:DM ratios. Importantly, this presentation was only partially linked to predicted affinity to the MHC-II molecule.

HIGHLIGHTS

Describe MHC-class II peptide repertoires from a unique HLA-DR4 cell line panel with increasing DO:DM ratios.

Demonstrate striking and divergent changes in MHC-II immunopeptidomes that result from the tuning function of DO:DM.

These findings bridge gap in understanding and predicting MHC-II antigen presentation.

GRAPHICAL ABSTRACT
Single cell profiling in COVID-19 associated acute kidney injury reveals patterns of tubule injury and repair in human
Authors: Legouis David , Rinaldi Anna , Arnoux Gregoire , Verissimo Thomas , Scotti-Gerber Jennifer , Faivre Anna , Schibler Manuel , Rinaldi Andrea , Naesens Maarten , Koppitch Kari , Pugin Jerome , McMahon Andrew P , Moll Solange , de Seigneux Sophie , Cippà Pietro E
Published: October 2021

The cellular mechanisms of kidney tubule repair are poorly characterized in human. Here, we applied single-nucleus RNA sequencing to analyze the kidney in the first days after acute injury in 5 critically ill patients with COVID-19. We identified abnormal proximal tubule cell states associated with injury, characterized by altered functional and metabolic profiles and by pro-fibrotic properties. Tubule repair involved the plasticity of mature tubule cells in a process of cell de-differentiation and re-differentiation, which displayed substantial similarities between mouse and man. In addition, in man we identified a peculiar tubule reparative response determining the expansion of progenitor-like cells marked by PROM1 and following a differentiation program characterized by the sequential activation of the WNT, NOTCH and HIPPO signaling pathways. Taken together, our analyses reveal cell state transitions and fundamental cellular hierarchies underlying kidney injury and repair in critically ill patients.
Green fluorescent protein-like pigments optimize the internal light environment in symbiotic reef building corals
Authors: Bollati Elena , Lyndby Niclas H. , D’Angelo Cecilia , Kühl Michael , Wiedenmann Jörg , Wangpraseurt Daniel
Published: October 2021

Pigments homologous to the Green Fluorescent Protein (GFP) have been proposed to fine-tune the internal light microclimate of corals, facilitating photoacclimation of photosynthetic coral symbionts (Symbiodiniaceae) to life in different reef habitats and environmental conditions. However, direct measurements of the in vivo light conditions inside the coral tissue supporting this conclusion are lacking. Here, we quantified the intra-tissue spectral light environment of corals expressing GFP-like proteins from widely different light regimes. We focus on (1) photoconvertible red fluorescent proteins (pcRFPs), thought to enhance photosynthesis in mesophotic habitats via wavelength conversion, and (2) chromoproteins (CPs), which provide photoprotection to the symbionts in shallow water via light absorption. Optical microsensor measurements indicated that both pigment groups strongly alter the coral tissue light environment. Estimates derived from light spectra measured in pcRFP-containing corals showed that fluorescence emission can contribute to >50% of orange-red light available to the photosynthetic symbionts at mesophotic depths. We further show that upregulation of pink CPs in shallow-water corals during bleaching leads to a reduction of orange light by 10-20% compared to low-CP tissue. Thus, screening by CPs has an important role in mitigating the light-enhancing effect of coral tissue scattering during bleaching. Our results provide the first experimental quantification of the importance of GFP-like proteins in fine-tuning the light microclimate of corals during photoacclimation.
The effects of age, sex, weight and breed on canid methylomes
Authors: Rubbi Liudmilla , Zhang Haoxuan , Feng Junxi , He Christopher , Kurnia Patrick , Ratan Prashansa , Tammana Aakash , Thompson Michael , Stahler Daniel , Ostrander Elaine A. , vonHoldt Bridgett , Pellegrini Matteo
Published: October 2021

Unlike genomes, which are static throughout the lifespan of an organism, DNA methylomes are dynamic. To study these dynamics we developed quantitative models that measure the effect of multiple factors on DNA methylomes including, age, sex, weight and genetics. We conducted our study in canids, which prove to be an ideal species to assess epigenetic moderators due to their extreme variability in size and well-characterized genetic structure. We collected buccal swabs from 217 canids (207 domestic dogs and 10 gray wolves) and used targeted bisulfite sequencing to measure methylomes. We also measured genotypes at over one thousand single nucleotide polymorphisms (SNPs). We found that DNA methylomes are strongly associated with age, enabling the construction of epigenetic clocks. We also show that methylomes are strongly impacted by sex, weight and sterilization status, leading to accurate predators of these factors. Methylomes are also affected by genetics and we observe multiple associations between SNP loci and methylated CpGs. Finally, we show that several factors moderate the relationship between epigenetic ages and real ages, such as body weight, which increases epigenetic aging. In conclusion, we demonstrate that the plasticity of DNA methylomes is impacted by myriad genetic and physiological factors, and that DNA methylation biomarkers are accurate predictors of age, sex and sterilization status.
Predicting increases in COVID-19 incidence to identify locations for targeted testing in West Virginia: A machine learning enhanced approach
Authors: Price Bradley S. , Khodaverdi Maryam , Halasz Adam , Hendricks Brian , Kimble Wesley , Smith Gordon S. , Hodder Sally L.
Published: October 2021

During the COVID-19 pandemic, West Virginia developed an aggressive SARS-CoV-2 testing strategy which included utilizing pop-up mobile testing in locations anticipated to have near-term increases in SARS-CXoV-2 infections. In this study, we describe and compare two methods for predicting near-term SARS-CoV-2 incidence in West Virginia counties. The first method, Rt Only, is solely based on producing forecasts for each county using the daily instantaneous reproductive numbers, Rt. The second method, ML+ Rt, is a machine learning approach that uses a Long Short-Term Memory network to predict the near-term number of cases for each county using epidemiological statistics such as Rt, county population information, and time series trends including information on major holidays, as well as leveraging statewide COVID-19 trends across counties and county population size. Both approaches used daily county-level SARS-CoV-2 incidence data provided by the West Virginia Department Health and Human Resources beginning April 2020. The methods are compared on the accuracy of near-term SARS-CoV-2 increases predictions by county over 17 weeks from January 1, 2021-April 30, 2021. Both methods performed well (correlation between forecasted number of cases and the actual number of cases week over week is 0.872 for the ML+Rt method and 0.867 for the Rt Only method) but differ in performance at various time points. Over the 17-week assessment period, the ML+Rt method outperforms the Rt Only method in identifying larger spikes. We also find that both methods perform adequately in both rural and non-rural predictions. Finally, we provide a detailed discussion on practical issues regarding implementing forecasting models for public health action based on Rt, and the potential for further development of machine learning methods that are enhanced by Rt.
A persistent behavioral state enables sustained predation of humans by mosquitoes
Authors: Sorrells Trevor R. , Pandey Anjali , Rosas-Villegas Adriana , Vosshall Leslie B.
Published: October 2021

Predatory animals pursue prey in a noisy sensory landscape, deciding when to continue or abandon their chase. The mosquito Aedes aegypti is a micropredator that first detects humans at a distance through sensory cues such as carbon dioxide. As a mosquito nears its target it senses more proximal cues such as body heat that guides it to a meal of blood. How long the search for blood continues after initial detection of a human is not known. Here we show that a 5-second optogenetic pulse of fictive carbon dioxide induced a persistent behavioral state in female mosquitoes that lasted for more than 10 minutes. This state is highly specific to females searching for a blood meal and was not induced in recently blood-fed females or in males, who do not feed on blood. In males that lack the gene fruitless, which controls persistent social behaviors in other insects, fictive carbon dioxide induced a long-lasting behavior response resembling the predatory state of females. Finally, we show that the persistent state triggered by detection of fictive carbon dioxide enabled females to engorge on a blood meal mimic offered up to 14 minutes after the initial 5-second stimulus. Our results demonstrate that a persistent internal state allows female mosquitoes to integrate multiple human sensory cues over long timescales, an ability that is key to their success as an apex micropredator of humans.
Cellular composition of human early and advanced coronary atherosclerotic lesions
Authors: Sharysh Diana , Markov Anton V. , Grigoryeva Evgeniya S. , Savelieva Olga E. , Sleptcov Aleksei A. , Zarubin Aleksei A. , Nazarenko Maria S.
Published: October 2021

Objective

Here, we identify and quantify leukocytes, macrophages, endothelial cells (ECs), and vascular smooth muscle cells (VSMCs) with contractile and macrophage-like phenotypes by flow cytometry to compare human early and advanced coronary atherosclerotic plaques.

Approach and Results

Sixteen coronary atherosclerotic lesions of 6 patients (3 women, 3 men, age 82 ± 9 years), including one case of restenosis after coronary stenting, were collected at autopsy. The cause of death of all patients was acute myocardial infarction. The lesions were categorized into early (EALs, n = 5) and advanced (AALs, n = 11) atherosclerotic stages. We analyzed a cell suspension stained with antibodies against CD45, CD68, CD31, and αSMA (ACTA2). We noted a decrease in the number of CD45+ cells and an increase in the CD45+CD68+ subpopulation of leukocytes from EALs to AALs. Numbers of CD45−αSMA+CD68+ cells positively correlated with the CD45+CD68+ macrophage number (r = 0.81; ρ = 0.64; p < 0.05) and the histological type of an atherosclerotic lesion (r = 0.81; ρ = 0.87; p < 0.05). As an interesting case, we analyzed cellular composition of the stented coronary artery and revealed significantly greater numbers of macrophages, αSMA+CD68+ VSMCs, and ECs in comparison with nonstented plaques.

Conclusions

Human early and advanced coronary atherosclerotic lesions differ in their counts of leukocytes and leukocyte subpopulations. For the first time, αSMA+CD68+ VSMCs were identified in early atherosclerotic stages of coronary arteries. Additionally, the restenotic coronary lesion contains mostly cells and is enriched in ECs, macrophages, and αSMA+CD68+ VSMCs in particular.
In pursuit of happiness at work: exploring the role of psychological capital and coping in managing COVID-19 stress among Indian employees
Authors: Pradhan Rabindra Kumar , Jandu Kailash , Panda Madhusmita , Hati Lopamudra , Mallick Manolina
Published: October 2021

Purpose

Employee happiness is crucial in any organization as happy employees are said to be more committed in their work. However, COVID-19 stress in the current situation is a major problem for employees and it can negatively influence their happiness level. Therefore, it is critical to understand how the stressful nature of the current pandemic threatens workplace happiness. Based on conservation of resources theory (Hobfoll, 1989), this study aims to examine the resources to be protected (i.e. psychological capital) and resource investment (i.e. coping) to ensure the happiness of the employees amidst a bio-psycho-socioeconomic crisis like COVID-19 pandemic. The study explores the mediating role of psychological capital and the moderating effect of coping on the relationship between COVID-19 stress and employee happiness.

Design/methodology/approach

Data were collected from the Indian working population by means of purposive sampling (N = 336). Standardized instruments were used to measure the variables under study. Data analysis were done using Statistical Package for Social Sciences 20.0 and Analysis of Moment Structure 20.0 software tools and PROCESS macro was used for mediation and moderation analysis.

Findings

Structural equation modelling analysis showed that COVID-19 stress negatively influenced employee happiness; whereas psychological capital partially mediated the relationship between these two variables. Further, coping was found to buffer against the harmful implications of COVID-19 stress on employee happiness.

Originality/value

In an effort to respond timely to the present pandemic scenario, the current study provides an account of the harmful effects of COVID-19-related stress on the workplace happiness of the Indian service sector employees. The study also offers insights into the possible mediating and moderating mechanisms in this relationship.
Switching behaviour in activity-based working environments: an exploration of the reasons and influencing factors
Authors: Häne Eunji , Windlinger Lukas
Published: October 2021

Purpose

A tendency that employees do not frequently switch between different activity settings was reported in previous studies, which are opposed to underlying assumptions of activity-based working (ABW) offices. Although ABW is increasingly becoming a standard office concept, employees’ switching behaviour has not been studied in depth. This study aims to understand employees’ switching behaviour by identifying reasons (not) to switch and various influencing factors of switching behaviour.

Design/methodology/approach

An online survey was conducted across Switzerland and Belgium, and 124 respondents participated in the questionnaire. The mismatch model was developed to examine whether the misfit between either activity or preference and work environment leads to switching to another place in the office.

Findings

Results show that most of the respondents switch multiple times a day, which runs counter to the previous studies. Furthermore, this study presented clear evidence that mandatory switching frequency is independent of various factors presented in the study, indicating that the distinction between mandatory and voluntary switching is valid. Besides, results identified privacy, acoustics, distraction, proximity to team/colleagues as reasons to switch and as reasons not to switch, place preference/attachment, proximity to the team were determined.

Originality/value

This study contributed to better understanding switching behaviour by defining, distinguishing switching behaviour, identifying reasons (not) to switch and influencing factors of switching frequency. In addition, this study compared the misfit between activity and environment and the misfit between preference and environment as push factors leading to switching behaviour. These findings can provide more knowledge of switching behaviour to workplace or facility management practitioners.
Knowledge management in family business succession: current trends and future directions
Authors: Ge Bingbing , Campopiano Giovanna
Published: October 2021

Purpose

This paper aims to review the literature on knowledge management in the family business, addressing the research question as follows: “How is knowledge managed across generations in the family business?” This study synthesizes the literature, highlighting the role of multiple stakeholders who affect knowledge management along with the phases of the succession process. Stemming from these findings and embracing a practice-based view, this paper offers research directions to guide future contributions on knowledge construction in the family business. The purpose of this study is not only to conclude the previous research but also to provide insights for future research directions and to provide practical implications.

Design/methodology/approach

Through a systematic integrative literature review, this paper collects map and analytically examine 63 published peer-reviewed articles related to knowledge management in the family business from 39 academic journals. This paper applies a rigorous approach to identify the sample of articles, map descriptive information of the reviewed literature and map theoretical contributions according to a multi-stakeholder and multi-stage framework.

Findings

The sampled articles are analyzed according to a multi-stakeholder and multi-stage framework inspired by Daspit et al. (2016). This study identifies critical gaps emerging from the analysis, thus opening the way to future research directions. In particular, this paper prompts scholars to advance the understanding of family-related knowledge and to clarify the assumptions on knowledge in their research.

Research limitations/implications

This paper contributes to the debate on knowledge management in the family business, by systematizing the current literature. In addition, this study embraces a “knowledge from practice perspective” and offers research directions to guide future contributions on knowledge construction in family business succession and potential areas to further management research investigating the role of family-related knowledge. Practical implications are also provided to benefit family businesses, consultants and policymakers.

Originality/value

This study provides a systematic integrative literature review of the articles published on knowledge management in family business according to a multi-stakeholder and multi-stage framework. Moreover, it draws an agenda for future research advancing a “knowledge from a practice perspective” in the family business literature.
Challenges of strategic corporate real estate management in Ghana
Authors: Boakye-Agyeman Naana Amakie , Bugri John Tiah , Gyamfi-Yeboah Frank
Published: October 2021

Purpose

Research shows that strategic corporate real estate management (SCREM) practice contributes to organizational performance. However, globally, SCREM practice is hindered by numerous challenges especially in developing countries such as Ghana. This study examines the challenges of SCREM practice in Ghana from business and corporate real estate managers’ perspectives.

Design/methodology/approach

A mixed-method design was adopted for the study. The largely quantitative study was supported with qualitative data. The multi-stage sampling technique was used to select respondents from 35 institutions in five sectors. The relative importance index, consensus/agreement framework and Mann–Whitney U test were used for analysis.

Findings

Analysis revealed that there is latent resistance to the provision of CRE policy, adequate authority and resources as well as resistance to change in organizational culture for the adoption of SCREM practice. The CRE management function is thus not well integrated into corporate activities. It is seen as a non-core organizational function merely providing physical space and support services.

Practical implications

The research has identified the challenges of SCREM and how these could be addressed to ensure that CRE is managed strategically to contribute effectively to organizational performance.

Originality/value

The paper is the first to identify the challenges of SCREM practice from business and CRE managers’ perspective in five sectors in Ghana, thus contributing to the limited literature on the subject globally.
Flower fields and pesticide use interactively shape pollen beetle infestation and parasitism in oilseed rape fields
Authors: Krimmer Elena , Martin Emily A. , Holzschuh Andrea , Krauss Jochen , Steffan‐Dewenter Ingolf
Published: October 2021

Pollen beetles (Brassicogethes spp.) are the main pests of oilseed rape (OSR, Brassica napus) in Europe and responsible for massive yield losses. Upcoming pesticide resistances highlight the need for other means of crop protection, such as natural pest control. Sown flower fields aim to counteract the decrease of insect biodiversity in agricultural landscapes by providing resources to ecosystem service providers. However, the optimal age and size of flower fields to increase natural pest control is still unclear.

We conducted experiments on 31 OSR fields located along a gradient of landscape‐scale semi‐natural habitat (SNH). OSR fields were located adjacent to flower fields which differed in age, continuity and size, or adjacent to crop fields or calcareous grasslands. Pesticide‐free areas were established to examine interactive effects of pesticide use and flower field characteristics. The abundance of pollen beetle adults and larvae, parasitism and superparasitism rates in OSR were recorded at increasing distances to the adjacent sites.

Flower fields and calcareous grasslands increased pollen beetle parasitism when compared to OSR fields neighbouring crop fields. The threshold for effective natural pest control of 35% could be reached in the pesticide‐free areas of OSR fields adjacent to calcareous grasslands and flower fields maintained continuously for at least 6 years. In pesticide‐sprayed areas, pollen beetle parasitism and superparasitism declined with increasing distance to the adjacent field. Furthermore, flower fields larger than 1.5 ha were able to improve pollen beetle parasitism more than smaller fields.

Synthesis and applications. To promote natural pest control in oilseed rape (OSR), large flower fields should be maintained for several years, to create stable habitats for natural enemies. The continuous maintenance of flower fields should be preferred, as ploughing and resowing after 5–6 years decreased the positive effects of the flower fields on natural pest control in adjacent OSR fields. However, pesticide use can abrogate positive effects of flower fields on pollen beetle parasitism. This study highlights that sown flower fields have the potential to increase natural pest control in OSR, but this potential is depending on its age, continuity and size and can be hindered by pesticide use.
Pain neuroscience education combined with usual treatment for fibromyalgia syndrome: A randomized controlled trial
Authors: Saracoglu Ismail , Leblebicier Merve Akdeniz , Yaman Fatima , Kavuncu Vural
Published: October 2021

Aim

The aim of this study was to investigate the effectiveness of pain neuroscience education (PNE) in addition to usual treatment in patients with fibromyalgia syndrome.

Methods

Forty patients were randomized into 2 groups. The experimental group underwent PNE sessions over 6 weeks in addition to pharmacological treatment, and the control group was given only pharmacological treatment. The primary outcome measure was functional status and the secondary outcome measures were widespread pain pressure threshold and kinesiophobia level. All assessments were conducted before the intervention and at the end of the 6th and 12th weeks by the same blinded researcher.

Results

The intervention group had significantly greater improvement than the control group in terms of the mean total scores in the Fibromyalgia Impact Questionnaire (P = .001) and the Tampa Scale of Kinesiophobia (P = .001) with large effect sizes. The intervention group also had significantly greater improvement in the pain pressure threshold values of the cervical (P = .040), thoracic (P = .001), lumbar (P < .001), elbow (P = .005) and calf (P = .006) regions with moderate‐to‐large effect sizes.

Conclusion

This study showed that the addition of 6‐week PNE sessions to pharmacological treatment was successful in improving functional status, widespread pain pressure threshold, and level of kinesiophobia in patients with fibromyalgia syndrome during a 12‐week follow‐up period.
Serum levels of inflammatory markers and HbA1c in patients with type 2 diabetes and apical periodontitis: Preliminary findings
Authors: Stys Liliana Preto Agostini , Böttcher Daiana Elisabeth , Scarparo Roberta Kochenborger , Gonçalves Waltrick Silvana Beltrami , de Figueiredo José Antonio Poli , Gomes Maximiliano Schünke , Campos Maria Martha
Published: October 2021

This pilot study assessed the glycaemic control and the serum levels of inflammatory mediators in type 2 diabetes (T2DM) patients with apical periodontitis (AP). Thirty individuals were divided into four groups: Healthy (H); with AP (AP); with T2DM (T2DM); and with T2DM and AP (T2DM‐AP). Demographic and pharmacological data were registered. The body mass index (BMI) and the levels of glycated haemoglobin (HbA1c) and IL‐1β, IL‐6, IL‐10, CCL3 and CCL4 were evaluated. AP areas were determined radiographically. Mean age was 64 ± 12 years, with 63% females. Most T2DM patients were under treatment with metformin and antihypertensives. BMI and H1bAc were significantly higher in T2DM patients in relation to H and AP groups. The AP areas were larger in the T2DM‐AP group, compared with the AP group. These preliminary findings suggest no influence of AP on glycaemic control or inflammatory levels amongst T2DM patients, although T2DM increased the AP severity.
Triangulation of pharmacoepidemiology and laboratory science to tackle otic quinolone safety
Authors: Winterstein Almut G. , Antonelli Patrick J.
Published: October 2021

Background

The scientific method requires studies with high internal and external validity. Though both are necessary, they do not go hand‐in‐hand: The more controlled a study is to enhance internal validity, the less applicable to real‐world clinical care, and vice versa. In the many instances where evidence from clinical trials is not available, scientific inference must rely on more extreme approaches on this spectrum, such as mechanistic (limited generalizability/strong bias control) and real‐world evidence (RWE) studies (higher generalizability/lesser bias control).

Objectives

Illustrate how triangulating mechanistic and RWE studies can enhance scientific inference by delivering the supporting evidence for both.

Methods

We describe our research on an unexpected and highly unlikely drug safety issue: the risk of tympanic membrane (TM) perforations resulting from otic quinolone therapy. Tightly controlled laboratory studies using cell culture and rodent models were complemented with pharmacoepidemiological studies of real‐world data to translate mechanistic findings and corroborate RWE.

Results

We present a cascade of mechanistic and RWE studies investigating fibroblast cytotoxicity, delayed healing of perforated TMs, and spontaneous TM perforations after otic quinolone exposure, all suggesting local tissue toxicity.

Conclusion

Triangulation of mechanistic and RWE studies allowed incremental progress toward robust evidence on otic quinolone toxicity.
What makes implementation intentions (in)effective for physical activity among older adults?
Authors: Warner Lisa Marie , Fleig Lena , Wolff Julia Katharina , Keller Jan , Schwarzer Ralf , Nyman Samuel R. , Wurm Susanne
Published: October 2021

Objectives

For most populations, implementation intentions (IIs) facilitate physical activity (PA). However, for older adults, previous studies found mixed evidence for the effectiveness of this behaviour change technique. To examine which characteristics of IIs predict successful enactment, the content of older participants’ IIs formed within a self‐regulatory intervention to prompt PA was analysed.

Design

A sample of N = 126 German speaking adults aged 64 and older formed up to six IIs for PA and reported their enactment 5 weeks later.

Methods

Controlling for age and sex, multilevel models tested associations between characteristics of IIs (e.g., chronological rank of II, hetero‐ and homogeneity, specificity, presence of certain cues) and enactment.

Results

Significantly related to enactment were: the chronological rank of an II (first IIs superior to last IIs), greater heterogeneity in activities, greater specificity of when‐cues, and greater use of pre‐existing routines.

Conclusions

Participants were more likely to enact their IIs 5 weeks later if they planned different (heterogeneous) activities, created IIs with more specific when‐cues (e.g., on Monday at 9 am), and in particular a routine (e.g., after breakfast). They also enacted the first three IIs (chronological rank of II) more often than the last three IIs. Future experimental studies should test whether providing instructions to create IIs based on the above significant characteristics lead to more effective health behaviour change among older adults.
Firm heterogeneity, technology adoption and the spatial distribution of population: Theory and measurement
Authors: Chernoff Alex W.
Published: October 2021

This paper develops and estimates an economic geography model featuring firm heterogeneity and technology adoption. I derive statistics that measure the effect of a new technology on productivity, welfare and the spatial distribution of the population. The empirical application estimates these effects using 19th‐century establishment‐level data on steam power in the Canadian manufacturing sector and township‐level population data. The results indicate that the introduction of steam power increased productivity by 22.9% and welfare by 4.9%. Comparing the model‐predicted and observed township population growth, I find that steam power accounts for 6.2% of the variation in observed population growth during this period.
Platelet‐rich plasma‐derived extracellular vesicles: A superior alternative in regenerative medicine?
Authors: Wu Jiuping , Piao Yingxin , Liu Qinyi , Yang Xiaoyu
Published: October 2021

Platelet‐rich plasma (PRP), due to its promising therapeutic properties, has been used in regenerative medicine for more than 30 years and numerous encouraging outcomes have been obtained. Currently, by benefiting from new insights into PRP mechanisms and the excellent performance of extracellular vesicles (EVs) in the field of tissue repair and regeneration, studies have found that a large number of EVs released from activated platelets also participate in the regulation of tissue repair. A growing number of preclinical studies are exploring the functions of PRP‐derived EVs (PRP‐EVs), especially in tissue regeneration. Here, we summarize the latest progress in PRP‐EVs as a superior alternative cell‐free therapeutic strategy in regenerative medicine, clarify their underlying molecular mechanisms, and discuss the advantages and limitations of the upcoming clinical applications. This review highlights the potential of PRP‐EVs to replace the application of PRP or even become a superior alternative in regenerative medicine.
Advising, gender, and performance: Evidence from a university with exogenous adviser–student gender match
Authors: Kato Takao , Song Yang
Published: October 2021

This paper provides the first causal evidence on the effects of gender match in the adviser–student relationship (as opposed to the well‐researched instructor–student relationship) on student outcomes along both the intensive and extensive margins. We analyze administrative data from a university with a faculty adviser assignment policy that makes gender pairing between advisers and students exogenous. We find that matching female students with female adviser has a positive and significant effect on retention and grade point average (GPA) upon graduation, particularly for students with academic challenges and non‐science, technology, engineering, and mathematics students. For female students with below‐median high school GPA, gender match is found to raise the odds of graduate school enrollments.
Public enterprise and the rise and fall of labor share
Authors: Bridgman Benjamin , Greenaway‐McGrevy Ryan
Published: October 2021

Developed economies experienced a rise and fall in labor share (LS) in the postwar period. We present a novel explanation of these trends – public enterprise employment. We document a link between it and both LS and wage compression in 15 developed nations. We then build a model that shows how overstaffing public enterprises can increase LS and reduce wage inequality. Overstaffing directly increases public enterprise LS and indirectly increases private sector LS by reducing available labor. We examine several public enterprise reforms. Consistent with the model’s predictions, reforms reduce public enterprise LS permanently and private sector LS temporarily.
A systematic literature review of participatory design studies involving teachers
Authors: Tuhkala Ari
Published: October 2021

Participatory design is a well‐known approach that involves stakeholders in designing technologies and other innovations. In education, participatory design is especially advocated for involving students with special needs. However, less attention has been paid to how participatory design can help in collaborations with teachers. This paper presents a systematic literature review of participatory design studies conducted between 2007 and 2017 that involved teachers. A comprehensive compilation of studies was collected from fourteen search engines and databases. Participatory design studies that involved teachers were analysed, organised and synthesised to produce an overview of the studies. The studies were organised into three thematic categories by research topics: (1) environments, (2) practices, and (3) technologies. Studies focusing on environments included for example teacher involvement in designing physical buildings and technologies that were integrated into the environment. Studies focusing on practices considered professional communities, instructional planning, and professional development programmes. Studies focusing on technologies included for example teacher involvement in designing assessment and monitoring tools, educational games, learning and teaching applications, security and safety technologies, and technology for special needs. This systematic literature review provides a solid starting point for future participatory design research involving teachers.
Long‐term efficacy, tolerability, and retention of brivaracetam in epilepsy treatment: A longitudinal multicenter study with up to 5 years of follow‐up
Authors: Strzelczyk Adam , Zaveta Clara , von Podewils Felix , Möddel Gabriel , Langenbruch Lisa , Kovac Stjepana , Mann Catrin , Willems Laurent M. , Schulz Juliane , Fiedler Barbara , Kurlemann Gerhard , Schubert‐Bast Susanne , Rosenow Felix , Beuchat Isabelle
Published: October 2021

Objective

This study was undertaken to evaluate the long‐term efficacy, retention, and tolerability of add‐on brivaracetam (BRV) in clinical practice.

Methods

A multicenter, retrospective cohort study recruited all patients who initiated BRV between February and November 2016, with observation until February 2021.

Results

Long‐term data for 262 patients (mean age = 40 years, range = 5–81 years, 129 men) were analyzed, including 227 (87%) diagnosed with focal epilepsy, 19 (7%) with genetic generalized epilepsy, and 16 (6%) with other or unclassified epilepsy syndromes. Only 26 (10%) patients had never received levetiracetam (LEV), whereas 133 (50.8%) were switched from LEV. The length of BRV exposure ranged from 1 day to 5 years, with a median retention time of 1.6 years, resulting in a total BRV exposure time of 6829 months (569 years). The retention rate was 61.1% at 12 months, with a reported efficacy of 33.1% (79/239; 50% responder rate, 23 patients lost‐to‐follow‐up), including 10.9% reported as seizure‐free. The retention rate for the entire study period was 50.8%, and at last follow‐up, 133 patients were receiving BRV at a mean dose of 222 ± 104 mg (median = 200, range = 25–400), including 52 (39.1%) who exceeded the recommended upper dose of 200 mg. Fewer concomitant antiseizure medications and switching from LEV to BRV correlated with better short‐term responses, but no investigated parameters correlated with positive long‐term outcomes. BRV was discontinued in 63 (24%) patients due to insufficient efficacy, in 29 (11%) for psychobehavioral adverse events, in 25 (10%) for other adverse events, and in 24 (9%) for other reasons.

Significance

BRV showed a clinically useful 50% responder rate of 33% at 12 months and overall retention of >50%, despite 90% of included patients having previous LEV exposure. BRV was well tolerated; however, psychobehavioral adverse events occurred in one out of 10 patients. Although we identified short‐term response and retention predictors, we could not identify significant predictors for long‐term outcomes.
Finding the perfect mismatch: Evaluating misspecification of population structure within spatially explicit integrated population models
Authors: Bosley Katelyn M. , Schueller Amy M. , Goethel Daniel R. , Hanselman Dana H. , Fenske Kari H. , Berger Aaron M. , Deroba Jonathan J. , Langseth Brian J.
Published: October 2021

Spatially stratified integrated population models (IPMs) can account for fine‐scale demographic processes and support spatial management for complex, heterogeneous populations. Although spatial IPMs may provide a more realistic representation of true population dynamics, few studies have evaluated the consequences associated with incorrect assumptions regarding population structure and connectivity. We utilized a simulation‐estimation framework to explore how mismatches between the true population structure (i.e. uniform, single population with spatial heterogeneity or metapopulation) and various parametrizations of an IPM (i.e. panmictic, fleets‐as‐areas or a spatially explicit, tag‐integrated model) impacted resultant fish population estimates. When population structure was incorrectly specified in the IPM, parameter estimates were generally unbiased at the system level, but were often biased for sub‐areas. Correctly specifying population structure in spatial IPMs led to strong performance, whereas incorrectly specified spatial IPMs performed adequately (and better than spatially aggregated counterparts). Allowing for flexible parametrization of movement rates (e.g. estimating age‐varying values) was more important than correctly identifying the population structure, and incorporation of tag‐recapture data helped movement estimation. Our results elucidate how incorrect population structure assumptions can influence the estimation of key parameters of spatial IPMs, while indicating that, even if incorrectly specified, spatial IPMs can adequately support spatial management decisions.
FOXOs: masters of the equilibrium
Authors: Gui Tianshu , Burgering Boudewijn M. T.
Published: October 2021

Forkhead box O (FOXO) transcription factors (TFs) are a subclass of the larger family of forkhead TFs. Mammalians express four members FOXO1, FOXO3, FOXO4, and FOXO6. The interest in FOXO function stems mostly from their observed role in determining lifespan, where in model organisms, increased FOXO activity results in extended lifespan. FOXOs act as downstream of several signaling pathway and are extensively regulated through post‐translational modifications. The transcriptional program activated by FOXOs in various cell types, organisms, and under various conditions has been described and has shed some light on what the critical transcriptional targets are in mediating FOXO function. At the cellular level, these studies have revealed a role for FOXOs in cell metabolism, cellular redox, cell proliferation, DNA repair, autophagy, and many more. The general picture that emerges hereof is that FOXOs act to preserve equilibrium, and they are important for cellular homeostasis. Here, we will first briefly summarize the general knowledge of FOXO regulation and possible functions. We will use genomic stability to illustrate how FOXOs ensure homeostasis. Genomic stability is critical for maintaining genetic integrity, and therefore preventing disease. However, genomic mutations need to occur during lifetime to enable evolution, yet their accumulation is believed to be causative to aging. Therefore, the role of FOXO in genomic stability may underlie its role in lifespan and aging. Finally, we will come up with questions on some of the unknowns in FOXO function, the answer(s) to which we believe will further our understanding of FOXO function and ultimately may help to understand lifespan and its consequences.