bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors in measuring lumbar spondylolisthesis with reference data from NHANES-II
Authors: Hipp John A. , Grieco Trevor F. , Newman Patrick , Patel Vikas V. , Reitman Charles A.
Published: August 2022

Background

Although spondylolisthesis, disc height loss, and abnormal disc angles are commonly assessed for in clinical practice and research studies, the factors that influence measurements are incompletely understood, and reference data representing a very large and diverse population are not available. Over 7000 lumbar spine x-rays were collected as part of the 2nd National Health and Nutrition Examination Survey (NHANES-II). This nationwide probability sample may facilitate development of robust reference data to objectively classify spondylolisthesis, disc heights, or disc angles as normal vs abnormal. Analysis of lumbar spine x-rays may also help to document whether disc heights and disc angles must be considered when assessing for spondylolisthesis.

Methods

Anatomic landmarks were obtained using neural networks and coded logic for L1 to S1 in the NHANES-II lumbar spine radiographs. Nine disc and sagittal plane offset (SPO) measurements were calculated from the landmarks. These data were trimmed to exclude abnormal discs and SPO. The factors that affect SPO were explored along with associations between the metrics and with age, sex, race, nation of origin and BMI. The prevalence of abnormalities was tabulated. Metrics were also calculated for previously analyzed lumbar flexion-extension x-rays to better understand the dependence of SPO on disc angles and disc heights. The errors that occur due to variability in radiographic projection were also assessed.

Results

SPO and disc metrics were obtained for 35,490 levels from 7,358 NHANES-II subjects who were 25 to 74 years old. Descriptive statistics for nine SPO and disc metrics were tabulated before and after trimming the data. Age, BMI, and sex were statistically significant but explained little of the variance in the metrics. SPO was significantly dependent on disc angle and height, though less so in the NHANES radiographs than in lumbar flexion-extension studies. Errors in the metrics due to out-of-plane imaging are generally small but can be large with extensive out-of-plane x-rays.

Discussion

The NHANES-II collection of lumbar x-rays allows for establishing reference data for SPO and disc metrics. These reference data allow for easily interpreted standardized reporting in units of std dev from average normal. SPO was significantly dependent on disc angle and disc height although the effect is small when there is limited flexion or extension. If SPO is being assessed from flexion or extension, a simple correction can be made. Caution is needed when interpreting measurements when the x-ray beam passes obliquely through the endplates or posterior wall (out-of-plane imaging).

Conclusions

The NHANES-II data may facilitate standardized assessments of SPO, disc heights and disc angles. Adjustments should be applied to SPO measurements if made from x-rays with the patient in flexed or extended positions.
The speed of vaccination rollout and the risk of pathogen adaptation
Authors: Gandon Sylvain , Lambert Amaury , Voinson Marina , Day Troy , Parsons Todd L.
Published: August 2022

Vaccination is expected to reduce disease prevalence and to halt the spread of epidemics. But pathogen adaptation may erode the efficacy of vaccination and challenge our ability to control disease spread. Here we examine the influence of the speed of vaccination rollout on the overall risk of pathogen adaptation to vaccination. We extend the framework of evolutionary epidemiology theory to account for the different steps leading to adaptation to vaccines: (1) introduction of a vaccine-escape variant by mutation from an endemic wild-type pathogen, (2) invasion of this vaccine-escape variant in spite of the risk of early extinction, (3) spread and, eventually, fixation of the vaccine-escape variant in the pathogen population. We show that the risk of pathogen adaptation is maximal for an intermediate speed of vaccination rollout. On the one hand, slower rollout decreases pathogen adaptation because selection is too weak to avoid early extinction of the new variant. On the other hand, faster rollout decreases pathogen adaptation because it reduces the influx of adaptive mutations. Hence, vaccinating faster is recommended to decrease both the number of cases and the likelihood of pathogen adaptation. We also show that pathogen adaptation is driven by its basic reproduction ratio, the efficacy of the vaccine and the effects of the vaccine-escape mutations on pathogen life-history traits. Accounting for the interplay between epidemiology, selection and genetic drift, our work clarifies the influence of vaccination policies on different steps of pathogen adaptation and allows us to anticipate the effects of public-health interventions on pathogen evolution.

Significance statement

Pathogen adaptation to host immunity challenges the efficacy of vaccination against infectious diseases. Are there vaccination strategies that limit the emergence and the spread of vaccine-escape variants? Our theoretical model clarifies the interplay between the timing of vaccine escape mutation events and the transient epidemiological dynamics following the start of a vaccination campaign on pathogen adaptation. We show that the risk of adaptation is maximized for intermediate vaccination coverage but can be reduced by a combination of non pharmaceutical interventions and faster vaccination rollout.
A metabolic map of the DNA damage response identifies PRDX1 in nuclear ROS scavenging and aspartate synthesis
Authors: Moretton Amandine , Kourtis Savvas , Calabrò Chiara , Zapater Antoni Gañez , Fontaine Frédéric , Müller André C. , Loizou Joanna I. , Sdelci Sara
Published: August 2022

While cellular metabolism impacts the DNA damage response, a systematic understanding of the metabolic requirements that are crucial for DNA damage repair has yet to be reported. Here, we investigate the metabolic enzymes and processes that are essential when cells are exposed to DNA damage. By integrating functional genomics with chromatin proteomics and metabolomics, we provide a detailed description of the interplay between cellular metabolism and the DNA damage response. Subsequent analysis identified Peroxiredoxin 1, PRDX1, as fundamental for DNA damage repair. During the DNA damage response, PRDX1 translocates to the nucleus where it is required to reduce DNA damage-induced nuclear reactive oxygen species. Moreover, PRDX1 regulates aspartate availability, which is required for the DNA damage-induced upregulation ofde novonucleotide synthesis. Loss of PRDX1 leads to an impairment in the clearance of DNA damage, accumulation of replicative stress and cell proliferation defects, thus revealing a crucial role for PRDX1 as a DNA damage surveillance factor.
The small cell lung cancer neuroendocrine transdifferentiation explorer
Authors: Cai Ling , Sondhi Varun , Zhu Mingrui , Akbay Esra , DeBerardinis Ralph J. , Xie Yang , Minna John D. , Xiao Guanghua , Gazdar Adi
Published: August 2022

SCLC is a high-grade neuroendocrine (NE) cancer that exhibits cellular plasticity. Transdifferention into non-NE cells creates considerable intra-tumoral heterogeneity, enhanced metastasis, greater tumor burden, and treatment resistance. Similar NE transdifferentiation has been observed in neuroblastoma (NBL). Targeting NE plasticity and cooperation between NE and non-NE cells in the tumor microenvironment may provide an avenue to enhance and restore sensitivity to available treatments. Although substantial transcriptomic changes take place upon NE transdifferentiation, conservation of these changes has not been investigated. In this study, we extensively curated genes associated with NE transdifferentiation in SCLC. We collected 35 datasets and compared the NE score-associated transcriptome across studies, for SCLC vs. NBL human tumors, human NBL tumors vs. cell lines, SCLC human tumors vs. tumors from genetically engineered mouse models (GEMMs), and SCLC GEMM uncultured cancer cells vs. cultured cancer cells. We have also created a user-friendly web application for researchers to explore these results. This work establishes a useful resource for researchers to understand the NE transdifferentiation landscape and explore context-dependent NE associations in SCLC and NBL.
Distribution and origins of Mycobacterium tuberculosis L4 in Southeast Asia
Authors: Ashton Philip M. , Cha Jaeyoon , Anscombe Catherine , Thuong Nguyen T.T. , Thwaites Guy E. , Walker Timothy M.
Published: August 2022

Molecular and genomic studies have revealed that Mycobacterium tuberculosis Lineage 4 (L4, Euro-American lineage) emerged in Europe before becoming distributed around the globe by trade routes, colonial migration, and other historical connections. Although L4 accounts for tens or hundreds of thousands of TB cases in multiple Southeast Asian countries, phylogeographic studies have either focussed on a single country or just included Southeast Asia as part of a global analysis. Therefore, we interrogated public genomic data to investigate the historical patterns underlying the distribution of L4 in Southeast Asia and surrounding countries. We downloaded 6037 genomes associated with 23 published studies, focusing on global analyses of L4 and Asian studies of M. tuberculosis. We identified 2256 L4 genomes including 968 from Asia. We show that 81% of L4 in Thailand, 51% of L4 in Vietnam and 9% of L4 in Indonesia belong to sub-clades of L4 that are rarely seen outside East and Southeast Asia. These sub-clades have been transmitted between East and Southeast Asian countries, with no recent European ancestor. Although there is considerable uncertainty about the exact direction and order of intra-Asian transmissions, due to differing sampling frames between countries, our analysis suggests that China may be the intermediate between Europe and Southeast Asia for two of the three predominantly East and Southeast Asian L4 sub-lineages. This new perspective on L4 in Southeast Asia raises the possibility of investigating host population specific evolution and highlights the need for more structured sampling from Southeast Asian countries to provide more certainty of the historical and current routes of transmission.
Polarized localization of phosphatidylserine in endothelium regulates Kir2.1
Authors: Ruddiman Claire A. , Peckham Richard , Luse Melissa A. , Chen Yen-Lin , Kuppusamy Maniselvan , Corliss Bruce , Hall P. Jordan , Lin Chien-Jung , Peirce Shayn M , Sonkusare Swapnil K. , Mecham Robert P. , Wagenseil Jessica E. , Isakson Brant E.
Published: August 2022

In the resistance artery endothelium, we show phosphatidylserine (PS) localizes to a specific subpopulation of myoendothelial junctions (MEJs), signaling microdomains that regulate vasodilation. In silico data has implied PS may compete with PIP2 binding on Kir2.1, a channel involved in vasodilatory signaling. We found 83.33% of Kir2.1-MEJs also contained PS, possibly indicating an interaction where PS regulates Kir2.1. Electrophysiology experiments on HEK cells demonstrate PS blocks PIP2 activation of Kir2.1, and addition of exogenous PS blocks PIP2-mediated Kir2.1 vasodilation in resistance arteries. Using a mouse model lacking canonical MEJs in resistance arteries (Elnfl/fl/Cdh5-Cre), PS localization in endothelium was disrupted and PIP2 activation of Kir2.1 was significantly increased. Taken together, our data suggests PS enrichment to MEJs inhibits PIP2-mediated activation of Kir2.1 to tightly regulate changes in arterial diameter, and demonstrates the intracellular lipid localization within endothelium is an important determinant of vascular function.
Plasma FIB milling for the determination of structures in situ
Authors: Berger Casper , Dumoux Maud , Glen Thomas , Yee Neville B.-y. , Mitchels John M. , Patáková Zuzana , Naismith James H , Grange Michael
Published: August 2022

Structural biology inside cells and tissues requires methods able to thin vitrified specimens to electron transparent thicknesses. Until now, focused ions beams based on gallium have been used. However, ion implantation, changes to surface chemistry and an inability to access high currents limit Gallium as an ion beam source. Here, we show that plasma-coupled ion sources can produce cryogenic lamella of vitrified human cells in a robust and automated manner, with quality sufficient for pseudo-atomic structure determination. In addition, these lamellae were produced in a prototype microscope equipped for long cryogenic run times (>1 week) and with multi-specimen support fully compatible with modern-day transmission electron microscopes. We demonstrate for the first time that plasma ion sources can be used for structural biology within cells, determining a structure in-situ to 4.9 Å and describing a workflow upon which different plasmas can be examined to streamline lamella fabrication further.
Stem cell-derived mouse embryos develop within an extra-embryonic yolk sac to form anterior brain regions and a beating heart
Authors: Amadei Gianluca , Handford Charlotte E , De Jonghe Joachim , Hollfelder Florian , Glover David , Zernicka-Goetz Magdalena
Published: August 2022

Embryo-like structures generated from stem cells can achieve varying developmental milestones, but none have been shown to progress through gastrulation, neurulation, and organogenesis.1–7 Here, we show that “ETiX” mouse embryos, established from embryonic stem cells aggregated with trophoblast stem cells and inducible extraembryonic endoderm stem cells, can develop through gastrulation and beyond to undertake neural induction and generate the progenitors needed to create the entire organism. The head-folds of ETiX embryos show anterior expression of Otx2, defining forebrain and midbrain regions that resemble those of the natural mouse embryo. ETiX embryos also develop beating hearts, trunk structures comprising a neural tube and somites, tail buds containing neuromesodermal progenitors and primordial germ cells, and gut tubes derived from definitive endoderm. A fraction of ETiX embryos show neural tube abnormalities, which can be partially rescued by treatment with the metabolically active form of folic acid, reminiscent of common birth defects and therapies in humans. Notably, ETiX embryos also develop a yolk sac with blood islands. Overall, ETiX embryos uniquely recapitulate natural embryos, developing further than any other stem-cell derived model, through multiple post-implantation stages and within extra-embryonic membranes.
Spatial structure may favor or disfavor microbial coexistence
Authors: Lobanov Alexander , Dyckman Samantha , Kurkjian Helen , Momeni Babak
Published: August 2022

Microbes often exist in spatially structured environments and many of their interactions are mediated through diffusible metabolites. How does such a context affect microbial coexistence? To address this question, we used a model in which the spatial distributions of species and diffusible interaction mediators are explicitly included. We simulated the enrichment process, examining how microbial species spatially reorganize and how eventually a subset of them coexist. In our model we find that slower motility of cells promotes coexistence by allowing species to co-localize with their facilitators and avoid their inhibitors. We additionally find that a spatially structured environment is more influential when species mostly facilitate each other, rather than when they are mostly competing. More coexistence is observed when species produce many mediators and consume some (not many or few) mediators, and when overall consumption and production rates are balanced. Interestingly, coexistence appears to be disfavored at low diffusion constants of diffusible mediators, because they lead to weaker interaction strengths. Overall, our results offer new insights into how production, consumption, motility, and diffusion intersect to determine microbial coexistence in a spatially structured environment.
Classroom experiments with artificial sweeteners: growing single crystals and simple calorimetry
Authors: Wouters Johan , Van Meervelt Luc
Published: August 2022

An easily accessible experimental set-up to grow large single crystals of two sweeteners readily available in supermarkets, erythritol and xylitol, is described. The crystallization of these compounds illustrates the principles of crystallization by evaporation. As these artificial sweeteners are also known to induce a cool sensation in the mouth, the crystal-growing experiment is complemented with a simple calorimetric set-up to demonstrate the endothermic nature of the dissolution of the selected sweeteners in a more quantitative approach by measuring the heat of dissolution (ΔH
diss). The choice of these two sweeteners also allows use of the freely available WebCSD and Mercury tools to visualize their three-dimensional structure, crystal packing and powder diffractograms, and to deepen stereochemical concepts such as stereoisomers and meso compounds.
Key facilitators to continuous improvement: a Spanish insight
Authors: Sanchez-Ruiz Lidia , Gomez-Lopez Raquel , Blanco Rojo Beatriz
Published: August 2022

Purpose

The aim of this paper is to analyse the nature of the facilitators of continuous improvement (CI), proposing a classification of them and identifying the different profiles of companies based on them.

Design/methodology/approach

To achieve this objective, first, a literature review was done in order to identify the main facilitators; second, some of them were included in a survey based on experts' opinions; third, a survey was conducted amongst people responsible for implementing CI; and finally factorial and cluster analysis were applied.

Findings

Based on the results, three main factors were identified: “cultural facilitators”, “tactical facilitators” and “human resources involvement facilitators”. Additionally, five clusters were defined.

Practical implications

As many companies still struggle when implementing CI, the results of this study can help all them to focus on the most important aspects in order to guarantee the sustainability of the CI system.

Originality/value

From a theoretical point of view, this work contributes to the CI field by analysing the nature of the main facilitators companies can find when implementing these initiatives. Thus, not only does this study provide a hierarchy of the most important facilitators, but also classifies them. As far as authors are concerned, this is the first attempt to categorise CI facilitators.
Lean on me when you’re not out: interactive effects of coworker support and concealment on transgender employees’ commitment and effort
Authors: Goldberg Caren , Willham Val
Published: August 2022

Purpose

Based on the job demands-resources (JD-R) model (Demerouti et al., 2001), the authors posited that concealment of one's transgender identity (a demand) would be negatively associated with work effort and commitment and that coworker support (a resource) would be positively related with those outcomes. In addition, the authors tested whether coworker support buffered the demand of maintaining secrecy as predicted by the JD-R model.

Design/methodology/approach

Relying on survey data from 89 transgender employees, the authors used Hayes' Process Model 1 to test the model.

Findings

Concealment was significantly related to both organizational commitment and work effort, but coworker support had no direct effect on either outcome. However, coworker support interacted with concealment, such that there were significant coworker support effects among trans employees who were out to none or some of their coworkers, but no significant effect among those who were out to all of their coworkers.

Originality/value

While prior studies have examined the importance of coworker support and outness, the authors add to the literature by examining the joint effect of these variables on transgender employees' work experiences. In addition, as prior research has been slow to examine behavioral work outcomes, the authors expand the criterion space by examining the simple and joint effects of outness and support on a previously ignored variable, work effort.
Effect of masculine eating and drinking beliefs on male consumers’ concern with healthy eating and binge drinking
Authors: Luna-Cortes Gonzalo , Aristizabal Cuellar José Alejandro
Published: August 2022

Purpose

The purpose of this paper is to examine the relationship of masculine eating/drinking beliefs on male consumers’ concern with unhealthy eating/drinking habits and, in turn, with binge drinking. Additionally, this research tests if and how a change in these beliefs influences binge drinking intention and intention to eat unhealthy food.

Design/methodology/approach

Three studies were conducted in Bogotá (Colombian males; convenience sampling). The purpose of Study 1 (N = 209) was to develop a scale to measure masculine eating/drinking beliefs. Study 2 (N = 191) tested the mediating role of concern with unhealthy eating/drinking habits in the relationship of masculine eating/drinking beliefs with binge drinking. Study 3 (N = 179) was an experimental study, which examined the effect of information about some negative consequences of masculine beliefs on the answers to the masculine eating/drinking beliefs inventory and, in turn, on binge drinking intention and intention to eat unhealthy food.

Findings

A one-dimensional (eight-items) scale was developed and validated. The results of this paper show that masculine eating/drinking beliefs are associated with lower concern with unhealthy eating/drinking and, in turn, with higher binge drinking. Information that influences these beliefs leads to lower binge drinking and unhealthy food ingestion intentions.

Research limitations/implications

This research presents the first scale that measures masculine eating/drinking beliefs. It provides initial evidence on how an intervention focused on the negative consequences of sexism can influence these beliefs, affecting binge drinking and overeating intentions.

Practical implications

This research provides new findings on a topic associated with several health problems in many countries, including the effect on consumers’ weight gaining and related illnesses.

Originality/value

This research presents the first scale that measures masculine eating/drinking beliefs. It provides initial evidence about factors (through mediating variables) that link masculine eating/drinking beliefs with some unhealthy eating/drinking habits. In addition, the results show how information about some negative consequences of these beliefs can influence consumers’ binge drinking and unhealthy food ingestion intentions, which leads to key recommendations for future interventions. As a result, this research provides new findings on a topic associated with several health problems in many countries, including the effect on consumers’ weight gaining and related illnesses.
Nutrition availability for those incarcerated in jail: Implications for mental health
Authors: Mommaerts Katherine , Lopez Nanette V. , Camplain Carolyn , Keene Chesleigh , Hale Ashley Marie , Camplain Ricky
Published: August 2022

Purpose

Using a seven-day cycle menu and commissary items at a rural county jail, this study aims to describe provisions of micronutrients known to be associated with mental health disorders and if they meet dietary guidelines.

Design/methodology/approach

The nutritional content of a seven-day cycle menu and four available commissary food packs were evaluated using NutritionCalc® Plus software (McGraw-Hill Education version 5.0.19) and compared to Dietary Reference Intakes (DRI).

Findings

Menu mean values of Vitamin B6, Vitamin B12, Vitamin C and zinc met DRI recommendations. However, Vitamin D (for men and women), magnesium (for men only) and omega-3s (for men only) did not meet the DRI recommendations.

Originality/value

As deficits of Vitamin D, magnesium and omega-3s are known to exacerbate bipolar disorder, anxiety and depression, small changes to food would increase the offerings and potential intake of nutrients that may improve mental health.
Advertising value of vlogs on destination visit intention: the mediating role of place attachment among Pakistani tourists
Authors: Abbasi Amir Zaib , Schultz Carsten D. , Ting Ding Hooi , Ali Faizan , Hussain Khalil
Published: August 2022

Purpose

Drawing on Ducoffe’s advertising value model, this study aims to integrate additional constructs (credibility, fantasy and visual appeal) as important antecedents to the perceived advertising value of vlogs. The study also examines the mediating role of place attachment between perceived advertising value and intention to visit a destination.

Design/methodology/approach

A total of 267 valid online questionnaires were collected among Pakistanis who (regularly, frequently, weekly or at least monthly) watch vlogs of tourist places on social networking sites and YouTube.

Findings

The empirical results using the partial least squares structural equation modeling approach show that informativeness, entertainment and credibility have significant positive effects, whereas irritation negatively impacts advertising value. The study also supports the positive effect of advertising value on visit intention and the mediating role of place attachment.

Originality/value

These findings reinforce a paradigm shift in advertising building on personal credibility, experiences and trustworthiness. This study contributes to the line of research that links promotional activities, destination image, tourists’ attitudes, visit intention and behavior.
Obtaining the best value for money through procurement planning: can procurement regulatory compliance intervene?
Authors: Changalima Ismail Abdi , Ismail Ismail Juma , Mwaiseje Shadrack Samwel
Published: August 2022

Purpose

While empirical studies establish the importance of procurement planning in achieving value for money (VfM) in procurement, there is scant evidence demonstrating a link between procurement planning and procurement regulatory compliance, and thus VfM. As a result, this study examined how procurement regulatory compliance can be applied when procurement practitioners in Tanzania seek to maximize VfM through procurement planning.

Design/methodology/approach

A cross-sectional research design was adopted from which data were collected once through a structured questionnaire. The structural equation modeling (SEM) and Hayes' PROCESS macro test for mediation analysis were used to analyze the collected data.

Findings

Procurement planning has a significant and positive relationship with procurement regulatory compliance (ß = 0.491, p < 0.001). Procurement regulatory compliance has a significant and positive relationship with VfM in procurement (ß = 0.586, p < 0.001). Results also show that procurement planning is a significant positive predictor of VfM (ß = 0.257, p = 0.005). Furthermore, the bootstrapping confidence intervals revealed that procurement regulatory compliance significantly mediates the relationship between procurement planning and VfM in procurement.

Research limitations/implications

Although the study was able to accomplish its overall objective, it is limited in terms of the geographical setting under which the study was conducted. Hence, the generalization of research results should be made with caution as each country has specific public procurement laws and regulations governing the conduct of procurement activities in the public sector.

Originality/value

The study contributes to the growing debate on achieving VfM in procurement activities. The study adds to the literature on public procurement by establishing the mediation effect of procurement regulatory compliance on the quest toward achieving VfM in public procurement.
A novel low‐density lipoprotein/fibrinogen apheresis method for chronic limb‐threatening ischemia in patients with poor options for revascularization: A multicenter, single‐arm clinical trial
Authors: Kobayashi Shuzo , Furukawa Masahide , Ichioka Shigeru , Horiuchi Katsumi , Kitano Ikuro , Fujii Miki , Ayabe Shinobu , Tanaka Rica , Ohura Norihiko , Ohura Takehiko
Published: August 2022

Introduction

Low‐density lipoprotein (LDL) apheresis is a treatment option for patients with unhealed chronic limb‐threatening ischemia (CLTI) after revascularization. The newly developed AS‐25 is a direct hemoperfusion‐type apheresis device that differs from conventional LDL apheresis therapy and is designed to specifically adsorb both LDL‐C and fibrinogen. We evaluate the efficacy and safety of AS‐25.

Methods

This study included 61 patients whose ulcers failed to heal after revascularization or were ineligible for revascularization. Of these, 50 were undergoing hemodialysis. The primary endpoint was the healing rate of a target lesion of interest (ulcer), using historical data as control.

Results

The ulcer healing rate of 45.9% was significantly higher than the historical data. No significant safety concerns were observed.

Conclusions

AS‐25 was effective in healing ulcers and preventing major amputation even in CLTI refractory patients on hemodialysis, thus showing potential clinical applicability and high significance.

Clinical Trial Registration

UMIN study ID UMIN000020336.
Prevalence of peripheral neuropathy and myopathy in patients post‐COVID‐19 infection
Authors: Saif Dalia S. , Ibrahem Reda Abdellatif , Eltabl Mohamed A.
Published: August 2022

Background

Severe acute respiratory syndrome (SARS‐CoV‐2), caused by the Coronavirus 2019 (COVID‐19), has become a life‐threatening epidemic, affecting multiple organs, including the nervous system. Recent studies have documented that COVID‐19‐associated peripheral neuropathy is a common and frequent problem, with central and peripheral nervous system complications.

Objective

This work aims to evaluate the peripheral nerves and muscle involvement after COVID‐19 infection, in addition to studying the prevalence rate and risk factors of their affection.

Methods

The study involved 400 patients, divided into 2 groups, with a history of COVID‐19 infection with or without symptoms of neuromuscular affection, and 30 gender‐ and age‐matched healthy volunteers were involved as controls. They were referred to the Department of Rheumatology and Rehabilitation for electro‐diagnosis. All participants performed complete clinical examination and laboratory measures with an electrophysiological study.

Results

The prevalence of peripheral neuropathy and myopathy in post‐COVID‐19 patients was 56.3% among all patients. A significant difference was detected among patients of both groups regarding serum creatine phosphokinase level, clinical signs, and electrophysiologic findings of neuropathy and myopathy compared to the control group, with more prominent features among the symptomatic group. Histories of hospitalization, severe and long‐lasting respiratory symptoms were risk factors for developing neuromuscular complications.

Conclusions

The present study could indicate that muscle involvement and peripheral nerve affection are common problems even among asymptomatic patients after COVID‐19 infection, especially in the presence of any risk factors.
Effect of dexamethasone on intraoperative remifentanil dose in total knee arthroplasty surgery under general anaesthesia
Authors: Gantzel Maria , Gasbjerg Kasper Smidt , Hägi‐Pedersen Daniel , Meyhoff Christian Sylvest , Olsen Markus Harboe , Mathiesen Ole , Jakobsen Janus Christian , Lunn Troels Haxholdt
Published: July 2022

Background

The effects of glucocorticoids may include both genomic and rapid nongenomic effects. The potential rapid analgesic effect during surgery has not previously been investigated. We aimed to explore the effect of dexamethasone on intraoperative infusion rate of remifentanil in patients undergoing total knee arthroplasty (TKA) surgery under general anaesthesia.

Methods

In this post hoc subgroup analysis, we included patients randomised in the DEX‐2‐TKA trial, who were operated under total intravenous anaesthesia with remifentanil and propofol. Trial medication, intravenous dexamethasone 24 mg or placebo, was administered immediately after anaesthesia onset. The primary outcome was the median weight‐corrected infusion rate of remifentanil during surgery. Secondary outcomes included median weight‐corrected infusion rate of propofol, median intraoperative bispectral index and time spent in the post‐anaesthesia care unit.

Results

Eighty‐seven patients were included in the analysis of the primary outcome. A significantly higher remifentanil infusion rate was observed in the dexamethasone group compared with the placebo group, p = .02. None of the secondary outcomes resulted in statistically significant differences between groups.

Conclusion

This explorative post hoc analysis of the randomised DEX‐2‐TKA trail showed that patients undergoing TKA surgery under general anaesthesia and who received dexamethasone seemed to have a higher remifentanil infusion rate compared with patients who received placebo. The clinical implications of the potentially increased remifentanil infusion rate need to be validated and explored further.

Clinical trial registration

ClinicalTrials.gov Identifier: NCT05002361 (12 August 2021).
The socio‐endocrine regulation of human growth
Authors: Hermanussen Michael , Erofeev Sergei , Scheffler Christiane
Published: July 2022

Aim

Growth is a multifarious phenomenon that has been studied by nutritionists, economists, paediatric endocrinologists; archaeologists, child psychologists and other experts. Yet, a unifying theory of understanding growth regulation is still lacking.

Method

Critical review of the literature.

Results

We summarise evidence linking social competition and its effect on hierarchies in social structures, with the neuronal networks of the ventromedial hypothalamus and body size. The endocrine signalling system regulating growth hormone, Insulin‐like‐Growth‐Factor1 and skeletal growth, is well conserved in the evolution of vertebrata for some 400 million years. The link between size and status permits adaptive plasticity, competitive growth and strategic growth adjustments also in humans. Humans perceive size as a signal of dominance with tallness being favoured and particularly prevalent in the upper social classes.

Conclusion

Westernised societies are competitive. People are tall, and “open to change.” Social values include striving for status and prestige implying socio‐economic domination. We consider the transition of political and social values following revolutions and civil wars, as key elements that interact with the evolutionarily conserved neuroendocrine competence for adaptive developmental plasticity, overstimulate the hypothalamic growth regulation and finally lead to the recent historic increases in average height.
KS0365, a novel activator of the transient receptor potential vanilloid 3 (TRPV3) channel, accelerates keratinocyte migration
Authors: Maier Marion , Olthoff Stefan , Hill Kerstin , Zosel Carolin , Magauer Thomas , Wein Lukas Anton , Schaefer Michael
Published: August 2022

Background and Purpose

Ca2+ signalling mediated by the thermosensitive, non‐selective, Ca2+‐permeable transient receptor potential channel TRPV3 is assumed to play a critical role in regulating several aspects of skin functions, such as keratinocyte proliferation, differentiation, skin barrier formation and wound healing. Studying the function of TRPV3 in skin homeostasis, however, is still constrained by a lack of potent and selective pharmacological modulators of TRPV3.

Experimental Approach

By screening an in‐house compound library using fluorometric intracellular Ca2+ assays, we identified two chemically related hits. The more potent and efficient TRPV3 activator 2‐(2‐chloro‐3‐isopropylcyclopent‐2‐en‐1‐yl)‐4‐methylphenol (KS0365) was further evaluated in fluo‐4‐assisted Ca2+ assays, different Ca2+ imaging approaches, electrophysiological studies, cytotoxicity and migration assays.

Key Results

KS0365 activated recombinant and native mouse TRPV3 more potently and with a higher efficacy compared with 2‐APB and did not activate TRPV2 or TRPV4 channels. The activation of TRPV3 by KS0365 super‐additively accelerated the EGF‐induced keratinocyte migration, which was inhibited by the TRP channel blocker ruthenium red or by siRNA‐mediated TRPV3 knockdown. Moreover, KS0365 induced strong Ca2+ responses in migrating front cells and in leading edges of keratinocytes.

Conclusions and Implications

The selective TRPV3 activator KS0365 triggers increases in [Ca2+]i with most prominent signals in the leading edge and accelerates migration of keratinocytes. TRPV3 activators may promote re‐epithelialization upon skin wounding.
HIDEA syndrome is caused by biallelic, pathogenic, rare or founder P4HTM variants impacting the active site or the overall stability of the P4H‐TM protein
Authors: Kraatari‐Tiri Minna , Soikkonen Leila , Myllykoski Matti , Jamshidi Yalda , Karimiani Ehsan G. , Komulainen‐Ebrahim Jonna , Kallankari Hanna , Mignot Cyril , Depienne Christel , Keren Boris , Nougues Marie‐Christine , Alsahlawi Zahra , Romito Antonio , Martini Javier , Toosi Mehran B. , Carroll Christopher J. , Tripolszki Kornelia , Bauer Peter , Uusimaa Johanna , Bertoli‐Avella Aida M. , Koivunen Peppi , Rahikkala Elisa
Published: July 2022

HIDEA syndrome is caused by biallelic pathogenic variants in P4HTM. The phenotype is characterized by muscular and central hypotonia, hypoventilation including obstructive and central sleep apneas, intellectual disability, dysautonomia, epilepsy, eye abnormalities, and an increased tendency to develop respiratory distress during pneumonia. Here, we report six new patients with HIDEA syndrome caused by five different biallelic P4HTM variants, including three novel variants. We describe two Finnish enriched pathogenic P4HTM variants and demonstrate that these variants are embedded within founder haplotypes. We review the clinical data from all previously published patients with HIDEA and characterize all reported P4HTM pathogenic variants associated with HIDEA in silico. All known pathogenic variants in P4HTM result in either premature stop codons, an intragenic deletion, or amino acid changes that impact the active site or the overall stability of P4H‐TM protein. In all cases, normal P4H‐TM enzyme function is expected to be lost or severely decreased. This report expands knowledge of the genotypic and phenotypic spectrum of the disease.
Microduplication of BTRC detected in a Chinese family with split hand/foot malformation type 3
Authors: Qiu Liyan , Li Caimin , Zheng Guiyun , Yang Tuyin , Yang Fang
Published: July 2022

Split hand/foot malformation (SHFM) is a clinically heterogeneous genetic disorder, which is mainly characterized by median clefts of the hand/feet due to the absence of the central digital rays. Several subgroups of SHFM have been identified, including SHFM1 to SHFM6. SHFM3 is an autosomal dominant disease, which has been identified to associate with a 500 kb microduplication at 10q24. The duplication involved several genes, including LBX1, BTRC, POLL, FBXW4, and so forth. In the study, using trio clinical exome sequencing, a 120 kb microduplication containing only BTRC were identified in a Chinese family affected with SHFM3. Further confirmation was performed using qRT‐PCR assay, which showed that the 120 kb duplication was co‐segregated with SHFM phenotypes in the family. It is the smallest duplication which has ever been reported relating to SHFM3. Furthermore, the transcription levels of BTRC mRNA in lymphocyte of the proband was significantly higher than that in the healthy control. The study provided evidence for the limb malformation caused by abnormal BTRC expression, and suggested that next generation sequencing could provide more precise diagnosis to SHFM3 patients.
Is a brain‐based understanding of addiction predominant? An assessment of addiction researchers' conceptions of addiction and their evaluation of brain‐based explanations
Authors: Ochterbeck Doris , Forberger Sarah
Published: August 2022

Introduction

Brain‐based explanations of addiction have become a prominent explanatory model in recent decades. Although opposing views have been published, there is no large‐scale study of researchers' opinions, unlike for treatment staff, the public and affected individuals. Therefore, this study aimed to examine international addiction researchers' perspectives on: (i) brain‐based explanations of addiction; (ii) the perceived dominance of the concept in science, society, treatment and among those affected; and (iii) researchers' general conception of addiction in terms of ontologies and causes.

Methods

A sample of 1440 international addiction researchers was compiled. Views were assessed online viaLimeSurveyusing a ‘mixed methods light’ approach (Likert‐type scales, free‐text fields). Qualitative content analyses of free‐text comments complemented descriptive statistics.

Results

One hundred and ninety researchers participated (13.19% response). The classification of substance use disorders as brain diseases/disorders was shared by about 60% of the respondents. Approximately 80% considered it the dominant view in science, but fewer in treatment, society and affected persons. Approximately 75% found it an oversimplification, but regarded it as helpful for understanding substance use disorders. Altogether, various biological, psychological and social factors were considered causal. Comments indicated that an over‐simplistic nature of brain‐based explanations of addiction was viewed as particularly problematic.

Discussion and Conclusions

A rejection of a simplistic view of addiction in favour of a multi‐causal concept in which the brain plays a role seems to be the majority view of participating researchers. Therefore, the orientation of future research, treatment and support for addicted persons need to be reconsidered accordingly.
Pulpal expression of erythropoietin and erythropoietin receptor after direct pulp capping in rat
Authors: Papic Milos , Zivanovic Suzana , Vucicevic Tamara , Papic Mirjana V. , Zdravkovic Dejan , Milivojevic Nevena , Virijevic Katarina , Zivanovic Marko , Mircic Aleksandar , Ljujic Biljana , Lukic Miodrag L. , Popovic Milica
Published: August 2022

This study aimed to evaluate the effect of direct pulp capping on the expression of erythropoietin (Epo) and Epo‐receptor (Epor) genes in relation to the expression of inflammatory and osteogenic genes in rat pulp. Dental pulps of the first maxillary molars of Wistar Albino rats were exposed and capped with either calcium hydroxide or mineral trioxide aggregate, or were left untreated. After 4 wk, animals were euthanized, and maxillae were prepared for histological and real‐time polymerase chain reaction analysis. Histological scores of pulp inflammation and mineralization, and relative expressions of Epo, Epor, inflammatory cytokines, and pulp osteogenic genes were evaluated. The capped pulps showed higher expressions of Epo, while the untreated pulps had the highest expression of Epor. Both calcium hydroxide and mineral trioxide aggregate downregulated the expression of tumor necrosis factor alpha compared to untreated controls, and upregulated transforming growth factor beta compared to healthy controls. Alkaline phosphatase expression was significantly higher in experimental groups. Relative expression of Epo negatively correlated with pulp inflammation, and positively correlated with pulp mineralization. Pulp exposure promoted expression of Epor and pro‐inflammatory cytokines, while pulp capping promoted expression of Epo, alkaline phosphatase, and downregulated Epor and pro‐inflammatory cytokines.
Pattern of caries lesions and oral health‐related quality of life throughout early childhood: A birth cohort study
Authors: Benelli Kelly da Rocha Gomes , Chaffee Benjamin W. , Kramer Paulo Floriani , Knorst Jessica Klöckner , Ardenghi Thiago Machado , Feldens Carlos Alberto
Published: August 2022

The aim of this study was to evaluate the impact of different patterns of dental caries on oral health‐related quality of life (OHRQoL) throughout early childhood. This birth cohort study followed 277 children from southern Brazil for 6 years. Demographic and socioeconomic variables were collected at birth. At age 3 years, children's dental caries experience was quantified by the decayed, missing, or filled teeth (dmft) index. At age 6 years, parents answered the Early Childhood Oral Health Impact Scale (ECOHIS). Poisson regression models were used to estimate associations between caries experience and later OHRQoL, presented as the ratio of ECOHIS scores between the groups. The prevalence of dental caries at 3 years of age was 37.5%. In children with caries, lesions only in anterior teeth, only in posterior teeth, and in both dental segments at age 3 were associated with age 6 ECOHIS scores that were 2.7, 7.8, and 6.2 times higher, respectively, than in children without dental caries experience. OHRQoL was worse among children with higher dmft scores. Dental caries lesions in posterior teeth by age 3 years was strongly predictive of adverse impacts on later OHRQoL, presumably as an indicator of continued disease experience in the intervening years.
Early onset of senescence and imbalanced epidermal homeostasis across the decades in photoexposed human skin: Fingerprints of inflammaging
Authors: Jarrold Bradley B. , Tan Christina Yan Ru , Ho Chin Yee , Soon Ai Ling , Lam TuKiet T. , Yang Xiaojing , Nguyen Calvin , Guo Wei , Chew Yap Ching , DeAngelis Yvonne M. , Costello Lydia , De Los Santos Gomez Paola , Przyborski Stefan , Bellanger Sophie , Dreesen Oliver , Kimball Alexa B. , Oblong John E.
Published: August 2022

Inflammaging is a theory of ageing which purports that low‐level chronic inflammation leads to cellular dysfunction and premature ageing of surrounding tissue. Skin is susceptible to inflammaging because it is the first line of defence from the environment, particularly solar radiation. To better understand the impact of ageing and photoexposure on epidermal biology, we performed a system biology‐based analysis of photoexposed face and arm, and photoprotected buttock sites, from women between the ages of 20s to 70s. Biopsies were analysed by histology, transcriptomics, and proteomics and skin surface biomarkers collected from tape strips. We identified morphological changes with age of epidermal thinning, rete ridge pathlength loss and stratum corneum thickening. The SASP biomarkers IL‐8 and IL‐1RA/IL1‐α were consistently elevated in face across age and cis/trans‐urocanic acid were elevated in arms and face with age. In older arms, the DNA damage response biomarker 53BP1 showed higher puncti numbers in basal layers and epigenetic ageing were accelerated. Genes associated with differentiation and senescence showed increasing expression in the 30s whereas genes associated with hypoxia and glycolysis increased in the 50's. Proteomics comparing 60's vs 20's confirmed elevated levels of differentiation and glycolytic‐related proteins. Representative immunostaining for proteins of differentiation, senescence and oxygen sensing/hypoxia showed similar relationships. This system biology‐based analysis provides a body of evidence that young photoexposed skin is undergoing inflammaging. We propose the presence of chronic inflammation in young skin contributes to an imbalance of epidermal homeostasis that leads to a prematurely aged appearance during later life.