bluuebunny/crossref_metadata_2025 huggingface dataset:
Anti-prion drugs do not improve survival in knock-in models of inherited prion disease
Authors: Walsh Daniel J. , Rees Judy R. , Mehra Surabhi , Bourkas Matthew E.C. , Kaczmarczyk Lech , Stuart Erica , Jackson Walker S. , Watts Joel C. , Supattapone Surachai
Published: September 2023

Prion diseases uniquely manifest in three distinct forms: inherited, sporadic, and infectious. Wild-type prions are responsible for the sporadic and infectious versions, while mutant prions cause inherited variants like fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (fCJD). Although some drugs can prolong prion incubation times up to four-fold in rodent models of infectious prion diseases, no effective treatments for FFI and fCJD have been found.

In this study, we evaluated the efficacy of various anti-prion drugs on newly-developed knock-in mouse models for FFI and fCJD. These models express bank vole prion protein (PrP) with the pathogenic D178N and E200K mutations. We applied various drug regimens known to be highly effective against wild-type prionsin vivoas well as a brain-penetrant compound that inhibits mutant PrPScpropagationin vitro. None of the regimens tested (Anle138b, IND24, Anle138b + IND24, cellulose ether, and PSCMA) significantly extended disease-free survival or prevented mutant PrPScaccumulation in either knock-in mouse model, despite their ability to induce strain adaptation of mutant prions. Paradoxically, the combination of Anle138b and IND24 appeared to accelerate disease by 16% and 26% in kiBVIE200Kand kiBVID178Nmice, respectively, and accelerated the aggregation of mutant PrP moleculesin vitro. Our results show that anti-prion drugs originally developed to treat infectious prion diseases do not necessarily work for inherited prion diseases, and that the recombinant sPMCA is not a reliable platform for identifying compounds that target mutant prions. This work underscores the need to develop therapies and validate screening assays specifically for mutant prions.
AMPK Regulates Phagophore-to-Autophagosome Maturation
Authors: Barnaba Carlo , Broadbent David G. , Perez Gloria I. , Schmidt Jens C.
Published: September 2023

Autophagy is an important metabolic pathway that can non-selectively recycle cellular material or lead to targeted degradation of protein aggregates or damaged organelles. Autophagosome formation starts with autophagy factors accumulating on lipid vesicles containing ATG9. These phagophores attach to donor membranes, expand via ATG2-mediated lipid transfer, capture cargo, and mature into autophagosomes, ultimately fusing with lysosomes for their degradation. Autophagy can be activated by nutrient stress, for example by a reduction in the cellular levels of amino acids. In contrast, how autophagy is regulated by low cellular ATP levels via the AMP-activated protein kinase (AMPK), an important therapeutic target, is less clear. Using live-cell imaging and an automated image analysis pipeline, we systematically dissect how nutrient starvation regulates autophagosome biogenesis. We demonstrate that glucose starvation downregulates autophagosome maturation by AMPK mediated inhibition of phagophores tethering to donor membranes. Our results clarify AMPK’s regulatory role in autophagy and highlight its potential as a therapeutic target to reduce autophagy.
Differential regulation by CD47 and thrombospondin-1 of extramedullary erythropoiesis in mouse spleen
Authors: Banerjee Rajdeep , Meyer Thomas J. , Cam Margaret C. , Kaur Sukhbir , Roberts David D.
Published: September 2023

Extramedullary erythropoiesis is not expected in healthy adult mice, but erythropoietic gene expression was elevated in lineage-depleted spleen cells fromcd47−/−mice. Expression of several genes associated with early stages of erythropoiesis was elevated in mice lacking CD47 or its signaling ligand thrombospondin-1, consistent with previous evidence that this signaling pathway inhibits expression of multipotent stem cell transcription factors in spleen. In contrast, cells expressing markers of committed erythroid progenitors were more abundant incd47−/−spleens but significantly depleted inthbs1−/−spleens. Single cell transcriptome and flow cytometry analyses indicated that loss of CD47 is associated with accumulation and increased proliferation in spleen of Ter119−CD34+progenitors and Ter119+CD34−committed erythroid progenitors with elevated mRNA expression of Kit, Ermap, and Tfrc. Induction of committed erythroid precursors is consistent with the known function of CD47 to limit the phagocytic removal of aged erythrocytes. Conversely, loss of thrombospondin-1 delays the turnover of aged red blood cells, which may account for the suppression of committed erythroid precursors inthbs1−/−spleens relative to basal levels in wild type mice. In addition to defining a role for CD47 to limit extramedullary erythropoiesis, these studies reveal a thrombospondin-1-dependent basal level of extramedullary erythropoiesis in adult mouse spleen.
MicroRNAs are necessary for the emergence of Purkinje cell identity
Authors: Zolboot Norjin , Xiao Yao , Du Jessica X. , Ghanem Marwan M. , Choi Su Yeun , Junn Miranda J. , Zampa Federico , Huang Zeyi , MacRae Ian J. , Lippi Giordano
Published: September 2023

Brain computations are dictated by the unique morphology and connectivity of neuronal subtypes, features established by closely timed developmental events. MicroRNAs (miRNAs) are critical for brain development, but current technologies lack the spatiotemporal resolution to determine how miRNAs instruct the steps leading to subtype identity. Here, we developed new tools to tackle this major gap. Fast and reversible miRNA loss-of-function revealed that miRNAs are necessary for cerebellar Purkinje cell (PC) differentiation, which previously appeared miRNA-independent, and resolved distinct miRNA critical windows in PC dendritogenesis and climbing fiber synaptogenesis, key determinants of PC identity. To identify underlying mechanisms, we generated a mouse model, which enables precise mapping of miRNAs and their targets in rare cell types. With PC-specific maps, we found that the PC-enriched miR-206 drives exuberant dendritogenesis and modulates synaptogenesis. Our results showcase vastly improved approaches for dissecting miRNA function and reveal that many critical miRNA mechanisms remain largely unexplored.

Highlights

Fast miRNA loss-of-function with T6B impairs postnatal Purkinje cell development

Reversible T6B reveals critical miRNA windows for dendritogenesis and synaptogenesis

Conditional Spy3-Ago2 mouse line enables miRNA-target network mapping in rare cells

Purkinje cell-enriched miR-206 regulates its unique dendritic and synaptic morphology
Articular cartilage corefucosylation regulates tissue resilience in osteoarthritis
Authors: Homan Kentaro , Onodera Tomohiro , Hanamatsu Hisatoshi , Furukawa Jun-ichi , Momma Daisuke , Matsuoka Masatake , Iwasaki Norimasa
Published: September 2023

This study aimed to investigate the glycan structural changes that occur before histological degeneration in osteoarthritis (OA) and to determine the mechanism by which these glycan conformational changes affect cartilage degeneration. An OA model was established in rabbits using mannosidase injection, which reduced high-mannose type N-glycans and led to cartilage degeneration. Further analysis of glycome in human OA cartilage identified specific corefucosylated N-glycan expression patterns. Inhibition of N-glycan corefucosylation resulted in unrecoverable cartilage degeneration, while cartilage-specific blocking of corefucosylation led to accelerated development of aging-associated and instability-induced OA models. We conclude that α1,6 fucosyltransferase is required postnatally to prevent preosteoarthritic deterioration of articular cartilage. These findings provide a novel definition of early OA and identify glyco-phenotypes of OA cartilage, which may distinguish individuals at higher risk of progression.
Bibliometric analysis of published articles on perinatal anxiety from 1920-2020
Authors: Dol Justine , Campbell-Yeo Marsha , Leahy-Warren Patricia , LaPointe Chloe Hambly , Dennis Cindy-Lee
Published: September 2023

Introduction

Trends and gaps in perinatal anxiety research remain unknown. The objective of this bibliometric review was to analyze the characteristics and trends in published research on perinatal anxiety to inform future research.

Methods

All published literature in Web of Science on perinatal anxiety from January 1, 1920 to December 31, 2020 were screened by two reviewers. VOSViewer was utilized to visualize linkages between publications. Bibliometric data were extracted from abstracts.

Results

The search strategy identified 4,561 publications. After screening, 2,203 publications related to perinatal anxiety were used for the visualization analysis. For the bibliometric data, 1,534 publications had perinatal anxiety as a primary focus. There were 7,910 different authors, over half named only once (55.5%), from 63 countries. 495 journals were identified, with over half (56.0%) publishing only one article. Most articles were published between 2011-2020 (75.9%). In terms of perinatal timing, over half (54.2%) published on antenatal anxiety. Only 6.0% of studies reported on perinatal anxiety in fathers and 56.5% reported on postpartum depression.

Limitations

Web of Science was solely used, and manual screening of each publication was required.

Conclusion

This bibliometric analysis found: (1) perinatal is a growing field of research, with publications increasing over time; (2) there is variation in authors and journals; (3) over half of the publications focus on antenatal anxiety; (4) paternal anxiety is understudied; and (5) only 6% of publications came from low and lower-middle income countries. Gaps related to maternal postnatal, and all paternal perinatal anxiety exist.
Networked proteins redundantly interact with VAP27 and RABG3 to regulate membrane tethering at the vacuole and beyond
Authors: Kaiser Sabrina , Mehlhorn Dietmar , Miranda Paulina Ramirez , Ries Fabian , Sommer Frederik , Schroda Michael , Schumacher Karin , Willmund Felix , Grefen Christopher , Scheuring David
Published: September 2023

Biological processes in eukaryotes depend on the spatio-temporal compartmentalization of their cells. Integrity and positioning of organelles on the other hand rely on the organization of the actin cytoskeleton. Previously, it has been shown that changes of the plants largest organelle, the vacuole, depend on a functional actin organization. The connection between actin filaments and the vacuole is established by the family of Networked (NET) 4 proteins and, consequently, altering NET4 abundance impacts vacuolar morphology. However, the precise regulatory mechanism is unknown and gene deletions ofNET4did not result in a global growth phenotype. Here, we show that NET4 functions redundantly with NET3, interacting with RABG3-GTPases at the vacuole to allow for homotypic fusion or, alternatively, the generation of endoplasmic reticulum (ER) - vacuole contact sites. We found that ER-resident NET3 is able to interact with RABG3 residing at the tonoplast and that NET4 interacts with the contact site protein VAP27-1 at the ER. Generation ofnet3 net4triple mutants by CRSIPR-guided mutagenesis helped us to overcome functional redundancy, resulting in impaired plant growth and development. Our results demonstrate how diversification ofNETgenes led to functional redundancy between different family members to create cellular plasticity of vascular plants. We hypothesize that establishment of a direct ER-vacuole connection enables direct lipid and protein transfer which is especially important in young and fast-growing cells. Availability of lipids would facilitate rapidly expanding vacuoles, which are the basis for high cell elongation rates and eventually fast plant growth.
Agile DMAIC cycle: incorporating process mining and support decision
Authors: Prado Renan Ribeiro Do , Boareto Pedro Antonio , Chaves Joceir , Santos Eduardo Alves Portela
Published: September 2023

Purpose

The aim of this paper is to explore the possibility of using the Define-Measure-Analyze-Improve-Control (DMAIC) cycle, process mining (PM) and multi-criteria decision methods in an integrated way so that these three elements combined result in a methodology called the Agile DMAIC cycle, which brings more agility and reliability in the execution of the Six Sigma process.

Design/methodology/approach

The approach taken by the authors in this study was to analyze the studies arising from this union of concepts and to focus on using PM tools where appropriate to accelerate the DMAIC cycle by improving the first two steps, and to test using the AHP as a decision-making process, to bring more excellent reliability in the definition of indicators.

Findings

It was indicated that there was a gain with acquiring indicators and process maps generated by PM. And through the AHP, there was a greater accuracy in determining the importance of the indicators.

Practical implications

Through the results and findings of this study, more organizations can understand the potential of integrating Six Sigma and PM. It was just developed for the first two steps of the DMAIC cycle, and it is also a replicable method for any Six Sigma project where data acquisition through mining is possible.

Originality/value

The authors develop a fully applicable and understandable methodology which can be replicated in other settings and expanded in future research.
The effect of NPD complexity on NPD performance via inter-organizational collaboration and conflict
Authors: Um Ki-Hyun
Published: September 2023

Purpose

This study develops a conceptualization of NPD (new product development) complexity and explores how inter-organizational collaboration and conflict influence NPD performance.

Design/methodology/approach

An empirical examination tests the proposed relationships in the context of Korean manufacturing firms, which currently engage in NPD projects with their key partners. Structural equation modeling (SEM) was used to examine the hypotheses.

Findings

The findings suggest that a higher level of NPD complexity simultaneously calls for inter-organizational collaboration and conflict, and these two factors influence NPD performance in a conflicting manner: inter-organizational collaboration serves as a driver, and inter-organizational conflict acts as a barrier against NPD performance.

Originality/value

This study provides answers to the academic and practical calls by providing how NPD complexity should be managed in a way to increase NPD performance. This study provides insight into how manufacturing firms form inter-organizational collaboration practices and why they need to mitigate inter-organizational conflict.
Income smoothing management and loan loss provisions in the banking system
Authors: Gómez-Ortega Alba , Licerán-Gutiérrez Ana , Horno-Bueno Maria de la Paz
Published: September 2023

Purpose

The “public interest” of financial institutions was used as an argument to intervene in accounting practices. The Bank of Spain's standard was not compatible with International Accounting Standard (henceforth IAS) 39 and the Spanish banking sector had become one of the most provisioned in Europe. This makes it an interesting case study of the relationship between provisioning and income smoothing. The 2008 financial crisis revealed that provisions were insufficient and a reinforcement regulation process began in 2012. This paper aims to examine whether, since 2012, the Bank of Spain's regulatory effort on impairment accounting standards has induced less income smoothing, correcting its countercyclical effect.

Design/methodology/approach

A regression model is applied during the period 2005–2020, to test whether there is a trend change in the correlation between the level of provisions and annual earnings in 2012.

Findings

The results show that from 2012 onwards (when the Bank of Spain reinforced the regulation on provisioning), there was a correction in income smoothing behaviour.

Originality/value

This study provides empirical evidence that reinforces the claim that accounting policy can affect decision-making accounting practices, in this particular case, at the Bank of Spain.
Influencer recommendation system: choosing the right influencer using a network analysis approach
Authors: Jha Abhishek Kumar , Ray Sanjog
Published: September 2023

Purpose

The rise of social media has led to the emergence of influencers and influencer marketing (IM) domains, which have become important areas of academic inquiry. However, despite its prominence as an area for study, several significant challenges must be addressed. One significant challenge involves identifying, assessing and recommending social media influencers (SMIs). This study proposes a semantic network model capable of measuring an influencer's performance on specific topics or subjects to address this issue. This study can assist managers in identifying suitable SMIs based on their estimated reach.

Design/methodology/approach

Data from popular YouTube influencers and publicly available performance measures (views and likes) are extracted. Second, the titles of the past videos made by the influencer are used to develop a semantic network connecting all the videos to other videos based on similarity measures. Third, the nearest neighbor approach extracts the neighbors of the target title video. Finally, based on the set of neighbors, a range prediction is made for the views and likes of the target video with the influencer.

Findings

The results show that the model can predict an accurate range of views and likes based on the suggested video titles and the content creator, with 69–78% accuracy across different influencers on YouTube.

Research limitations/implications

The current study introduces a novel and innovative approach that exploits the textual association between a SMI's previous content to forecast the outcome of their future content. Although the findings are encouraging, this research recognizes various constraints that upcoming researchers may tackle. Forecasting views of posts concerning novel subjects and precisely adjusting video view counts based on their age constitute two primary limitations of this study.

Practical implications

Managers interested in hiring influencers can employ the suggested approach to evaluate an influencer's potential performance on a specific topic. This research aids managers in making informed decisions regarding influencer selection, utilizing data-based metrics that are simple to comprehend and explain.

Originality/value

The study contributes to outreach evaluation and better estimating the impact of SMIs using a novel semantic network approach.
Managerial sentiment and corporate risk-taking: evidence from Chinese listed companies’ annual reports
Authors: Qin Zhihao , Cui Menglin , Yan Jiaqi , Niu Jie
Published: September 2023

Purpose

This paper aims to examine whether managerial sentiment, extracted from annual reports, is associated with corporate risk-taking in the context of Chinese companies. This study expands the vein of literature on overconfidence theory.

Design/methodology/approach

By leveraging textual analysis on Chinese listed companies’ annual reports, the authors construct firm-level managerial sentiment during 2007 and 2021 to examine how managerial sentiment influences corporate risk-taking after control for firm characteristics. Corporate risk-taking is denoted by corporate investment engagements: capital expenditures and net fixed asset investment.

Findings

Results show that incentives for corporate risk-taking are likely to increase with the positive managerial sentiment and decrease with the negative sentiment in companies’ annual reports. Positive managerial sentiment is associated with over-/under-investment and low/high investment efficiency. Further additional tests show that the managerial sentiment effect only holds during low economic uncertain years and samples of private-owned firms. Furthermore, the robust tests indicate that there is no endogenous issue between managerial sentiment and corporate risk-taking.

Research limitations/implications

Annual report textual-based managerial sentiment may not perfectly reflect managers’ lower frequency sentiment (e.g. weekly, monthly and quarterly sentiment). Future studies could attempt to capture managers’ on-time sentiment by using media sources and corporate disclosures.

Practical implications

To the best of the authors’ knowledge, this paper is the first research to provide insights into supervising managers’ corporate decisions by observing their textual information usage in corporate disclosure. Moreover, the approach of measuring managerial sentiment might be a solution to monitoring managerial class.

Originality/value

This paper contributes to the literature on accounting and finance studies, adding another piece of empirical evidence on content analysis by examining a unique language and institutional context (i.e. China). Besides, the paper notes that in line with the English version disclosure, based on Chinese semantic words, managerial sentiment in the Chinese-speaking world has magnitude on corporate decisions. The research provides insights into supervising managers’ corporate decisions by observing their textual information usage in corporate disclosure. Moreover, the approach to measuring managerial sentiment may be a practical solution to monitoring managerial class.
Reframing the English Foreign Act of State Doctrine
Authors: Lando Massimo
Published: September 2023

This article proposes a way to reframe the English foreign act of State doctrine. The doctrine is an established rule of English common law but its contours and application remain ill‐defined, despite the Supreme Court's restatement in Belhaj v Straw. The doctrine in its current form emerges from the accretion of precedents over some 350 years, but still lacks a unifying framework bringing its different strands together. This article argues that English courts should reframe the doctrine by reference to the distinction between elements of a rule that are embedded in its definition, called ‘limitations’, and elements of a rule that exist separately from it, called ‘exceptions’. This distinction has been developed in legal philosophy to classify the elements of wrongs as definitional elements, constitutive of liability, and defences, defeating liability. Reframed according to this distinction, the English foreign act of State doctrine can be streamlined into one, single rule, instead of the three rules set out in Belhaj v Straw. This reframing has implications for the doctrine's characterisation as one of justiciability, abstention or restraint, and its compatibility with the duty to do justice, including under the European Convention on Human Rights.
Functional diversity metrics can perform well with highly incomplete data sets
Authors: Stewart Kerry , Carmona Carlos P. , Clements Chris , Venditti Chris , Tobias Joseph A. , González‐Suárez Manuela
Published: September 2023

Characterising changes in functional diversity at large spatial scales provides insight into the impact of human activity on ecosystem structure and function. However, the approach is often based on trait data sets that are incomplete and unrepresentative, with uncertain impacts on functional diversity estimates.

To address this knowledge gap, we simulated random and biased removal of data from three empirical trait data sets: an avian data set (9579 species), a plant data set (2185 species) and a crocodilian data set (25 species). For these data sets, we assessed whether functional diversity metrics were robust to data incompleteness with and without using imputation to fill data gaps. We compared two metrics each calculated with two methods: functional richness (calculated with convex hulls and trait probabilities densities) and functional divergence (calculated with distance‐based Rao and trait probability densities).

Without imputation, estimates of functional diversity (richness and divergence) for birds and plants were robust when 20%–70% of species had missing data for four out of 11 and two out of six continuous traits, respectively, depending on the severity of bias and method used. However, when missing traits were imputed, functional diversity metrics consistently remained representative of the true value when 70% of bird species were missing data for four out of 11 traits and when 50% of plant species were missing data for two out of six traits. Trait probability densities and distance‐based Rao were particularly robust to missingness and bias when combined with imputation. Convex hull‐based estimations of functional richness were less reliable. When applied to a smaller data set (crocodilians, 25 species), all functional diversity metrics were much more sensitive to missing data.

Expanding global morphometric data sets to represent more taxa and traits, and to quantify intraspecific variation, remains a priority. In the meantime, our results show that widely used methods can successfully quantify large‐scale functional diversity even when data are missing for half of species, provided that missing traits are estimated using imputation. We recommend the use of trait probability densities or distance‐based Rao when working with large incomplete data sets and filling data gaps with imputation.
Prehospital lung ultrasound in acute heart failure: Impact on diagnosis and treatment
Authors: Russell Frances M. , Supples Michael , Tamhankar Omkar , Liao Mark , Finnegan Patrick
Published: September 2023

Objective

Patients with acute heart failure (AHF) are commonly misdiagnosed and undertreated in the prehospital setting. These delays in diagnosis and treatment have a direct negative impact on patient outcomes. The goal of this study was to determine the diagnostic accuracy of paramedics with and without the use of lung ultrasound (LUS) for the diagnosis of AHF in patients with dyspnea in the prehospital setting. Secondarily, we assessed LUS impact on rate of and time to initiation of HF therapies.

Methods

This was a prospective interventional study on a consecutive sample of patients transported to the hospital by one emergency medical services agency. Adult patients (>18 years) with a chief complaint of dyspnea were included. LUS was performed by trained paramedics and was defined as positive for AHF if both anterior–superior lung zones had greater than or equal to three B‐lines or bilateral B‐lines were visualized on a four‐view protocol. Paramedic diagnosis was compared to hospital discharge diagnosis which served as the criterion standard.

Results

Of the 264 included patients, 94 (35%) had a final diagnosis of AHF. Forty total patients had a LUS performed; 17 of these patients had a final diagnosis of AHF. Sensitivity and specificity for AHF by paramedics were 23% (95% confidence interval [CI] 0.14–0.34) and 97% (95% CI 0.92–0.99) without LUS and 71% (95% CI 0.44–0.88) and 96% (95% CI 0.76–0.99) with the use of LUS. In the 94 patients with AHF, 14% (11/77) received HF therapy prehospital without the use of LUS and 53% (9/17) with the use of LUS. LUS improved frequency of treatment by 39%. Median time to treatment was 21 min with LUS and 169 min without.

Conclusions

LUS improved paramedic sensitivity and accuracy for diagnosing AHF in the prehospital setting. LUS use led to higher rates of prehospital HF therapy initiation and significantly decreased time to treatment.
Beyond high‐risk: analysis of the outcomes of extreme‐risk patients in the National Emergency Laparotomy Audit
Authors: Javanmard‐Emamghissi H. , Doleman B. , Lund J. N. , Lockwood S. , Hare S. , Pearce L. , Moug S. , Tierney G. M.
Published: September 2023

Patients who require emergency laparotomy are defined as high risk if their 30‐day predicted risk of mortality is ≥ 5%. Despite a large difference in the characteristics of patients with a mortality risk score of between 5% and 50%, these outcomes are aggregated by the National Emergency Laparotomy Audit (NELA). Our aim was to describe the outcomes of the cohort of patients at extreme risk of death, which we defined as having a NELA‐predicted 30‐day mortality of ≥ 50%. All patients enrolled in the NELA database between December 2012 and 2020 were included. We compared patient characteristics; length of hospital stay; rates of unplanned return to the operating theatre; and 90‐day survival in extreme‐risk groups (predicted ≥ 50%) and high‐risk patients (predicted 5–49%). Of 161,337 patients, 5193 (3.2%) had a predicted mortality of ≥ 50%. When patients were further subdivided, 2437 (47%) had predicted mortality of 50–59% (group 50–59); 1484 (29%) predicted mortality of 60–69% (group 60–69); 840 (16%) predicted mortality of 70–79% (group 70–79); and 423 (8%) predicted mortality of ≥ 80% (group 80+). Extreme‐risk patients were significantly more likely to have been admitted electively than high‐risk patients (p < 0.001). Length of stay increased from a median (IQR [range]) of 26 (16–43 [0–271]) days in group 50–59 to 35 (21–56 [0–368]) days in group 80+, compared with 17 (10–30 [0–1136]) days for high‐risk patients. Rates of unplanned return to the operating theatre were higher in extreme‐risk groups compared with high‐risk patients (11% vs. 8%). The 90‐day survival was 43% in group 50–59, 34% in group 60–69, 27% in group 70–79 and 17% in group 80+. These data underscore the need for a differentiated approach when discussing risk with patients at extreme risk of mortality following an emergency laparotomy. Clinicians should focus on patient priorities on quantity and quality of life during informed consent discussions before surgery. Future work should extend beyond the immediate postoperative period to encompass the longer‐term outcomes (survival and function) of patients who have emergency laparotomies.
The role of platelet P2Y12 receptors in inflammation
Authors: Parker William A. E. , Storey Robert F.
Published: September 2023

Inflammation is a complex pathophysiological process underlying many clinical conditions. Platelets contribute to the thrombo‐inflammatory response. Platelet P2Y12 receptors amplify platelet activation, potentiating platelet aggregation, degranulation and shape change. The contents of platelet alpha granules, in particular, act directly on leucocytes, including mediating platelet–leucocyte aggregation and activation via platelet P‐selectin. Much evidence for the role of platelet P2Y12 receptors in inflammation comes from studies using antagonists of these receptors, such as the thienopyridines clopidogrel and prasugrel, and the cyclopentyltriazolopyrimidine ticagrelor, in animal and human experimental models. These suggest that antagonism of P2Y12 receptors decreases markers of inflammation with some evidence that this reduces incidence of adverse clinical sequelae during inflammatory conditions. Interpretation is complicated by pleiotropic effects such as those of the thienopyridines on circulating leucocyte numbers and of ticagrelor on adenosine reuptake. The available evidence suggests that P2Y12 receptors are prominent mediators of inflammation and P2Y12 receptor antagonism as a potentially powerful strategy in a broad range of inflammatory conditions.

LINKED ARTICLES

This article is part of a themed issue on Platelet purinergic receptor and non‐thrombotic disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.4/issuetoc
Endoscopic pressure study integrated system for the diagnosis of achalasia
Authors: Nishikawa Yohei , Inoue Haruhiro , Shimamura Yuto , Navarro Marc Julius , Kawamata Natsuki , Azuma Daisuke , Ushikubo Kei , Kimoto Yoshiaki , Yamamoto Kazuki , Fujiyoshi Yusuke , Okada Hiroki , Tanaka Ippei , Toshimori Akiko , Tanabe Mayo , Onimaru Manabu
Published: September 2023

Objectives

The endoscopic pressure study integrated system (EPSIS) is a novel diagnostic tool used to evaluate lower esophageal sphincter (LES) function. EPSIS allows the measurement of intragastric pressure (IGP) during gastric insufflation through esophagogastroduodenoscopy (EGD) and records its pressure waveform. This study aimed to assess the usefulness and applicability of EPSIS as an adjunct diagnostic modality for achalasia.

Methods

This case–control study was conducted using a database of patients who underwent EGD, barium swallow (BS), high‐resolution manometry (HRM), and EPSIS between January 2022 and December 2022. The achalasia (experimental) group (n = 35) consisted of patients with a definitive diagnosis of achalasia. The control group (n = 34) consisted of patients with no abnormalities in EGD, BS, or HRM and no abnormal acid reflux confirmed with 24‐h pH‐impedance monitoring. EPSIS findings were compared between the two groups and characterized by the waveform pattern (uphill or flat), maximum IGP (IGP‐Max), pressure difference, and the gradient of the waveform.

Results

All patients in the achalasia group showed an uphill pattern, in contrast to 21 patients (61.8%) in the control group. IGP‐Max demonstrated the best diagnostic accuracy for achalasia, with a cut‐off value of 15.8 mmHg (100% sensitivity, 58.8% specificity, and area under the curve [AUC] 0.78). The pressure gradient also demonstrated good diagnostic accuracy, with a cut‐off value of 0.40 mmHg/s (80% sensitivity, 61.8% specificity, and AUC 0.76).

Conclusion

This study demonstrated that EPSIS can be applied as a diagnostic modality in patients with achalasia.
PERcutaneous transhepatic CHOLangioscopy using a new single‐operator short cholangioscope (PERCHOL): European feasibility study
Authors: Pérez‐Cuadrado‐Robles Enrique , Phillpotts Simon , Bronswijk Michiel , Conrad Claudio Cim , Binda Cecilia , Monino Laurent , Basiliya Kirill , Hollenbach Marcus , Papaefthymiou Apostolis , Alric Hadrien , Quénéhervé Lucille , Di Gaeta Alessandro , Pioche Mathieu , Khani Aria , Lorenzo Diane , Moreels Tom G. , Rahmi Gabriel , Boeken Tom , Fabbri Carlo , Prat Frédéric , Laleman Wim , Cellier Christophe , Van der Merwe Schalk , Webster George , Ellrichmann Mark
Published: September 2023

Objectives

A new short device for percutaneous endoscopic cholangioscopy was recently developed. However, feasibility and safety has not yet been evaluated. The aim of this study was to assess clinical success, technical success, and adverse events (AEs).

Methods

This observational multicenter retrospective study included all patients who underwent percutaneous cholangioscopy using a short cholangioscope between 2020 and 2022. The clinical success, defined as the complete duct clearance or obtaining at least one cholangioscopy‐guided biopsy, was assessed. The histopathological accuracy, technical success, and the AE rate were also evaluated.

Results

Fifty‐one patients (60 ± 15 years, 45.1% male) were included. The majority of patients had altered anatomy (n = 40, 78.4%), and biliary stones (n = 34, 66.7%) was the commonest indication. The technique was predominantly wire‐guided (n = 44, 86.3%) through a percutaneous sheath (n = 36, 70.6%) following a median interval of 8.5 days from percutaneous drainage. Cholangioscopy‐guided electrohydraulic lithotripsy was performed in 29 cases (56.9%), combined with a retrieval basket in eight cases (27.6%). The clinical success was 96.6%, requiring a median of one session (range 1–3). Seventeen patients (33.3%) underwent cholangioscopy‐guided biopsies. There were four (7.8%) cholangioscopy‐related AEs (cholangitis and peritonitis). Overall, the technical success and AE rates were 100% and 19.6%, respectively, in a median follow‐up of 7 months.

Conclusion

Percutaneous endoscopic cholangioscopy with a new short device is effective and safe, requiring a low number of sessions to achieve duct clearance or accurate histopathological diagnosis.
Torque teno virus‐DNA load as individual cytomegalovirus risk assessment parameter upon allogeneic hematopoietic stem cell transplantation
Authors: Spiertz Arlene , Tsakmaklis Anastasia , Farowski Fedja , Knops Elena , Heger Eva , Wirtz Maike , Kaiser Rolf , Holtick Udo , Vehreschild Maria J. G. T. , Di Cristanziano Veronica
Published: September 2023

Background

Immune recovery following allogeneic hematopoietic stem cell transplantation (allo‐HSCT) decisively influences the occurrence of opportunistic infections, one of the leading causes of death among this group of patients. Yet, today, there are no laboratory parameters mirroring immune function sufficiently. Torque teno virus (TTV) has already proven itself as a functional immune marker in other settings.

Aims

In this analysis, we investigated whether monitoring of TTV‐DNA load in whole blood is able to provide additional information on the capacity of the immune system to control cytomegalovirus (CMV) replication in allo‐HSCT recipients.

Methods

Whole blood samples from 59 patients were collected upon allo‐HSCT (between Day −7 and +10), on Day +14, +21, +28, +56, +90, and +365 post‐transplant. TTV‐DNA loads and other relevant clinical information were correlated with the risk of CMV infections or reactivations, defined by evidence of viral replication in blood.

Results

CMV serostatus of the recipient and a TTV load below 1000 copies/mL upon allo‐HSCT were significantly associated with an increased incidence of CMV infection or reactivation.

Conclusions

Quantification of TTV load in the early phase of allo‐HSCT procedure could provide additional information in order to identify patients at risk for CMV infection or reactivation.
Dermoscopy of atypical pigmented lesions of the face: Variation according to facial areas
Authors: Tognetti Linda , Cartocci Alessandra , Cinotti Elisa , D'Onghia Martina , Żychowska Magdalena , Moscarella Elvira , Dika Emi , Farnetani Francesca , Guida Stefania , Paoli John , Lallas Aimilios , Tiodorovic Danica , Stanganelli Ignazio , Longo Caterina , Suppa Mariano , Zalaudek Iris , Argenziano Giuseppe , Perrot Jean Luc , Rubegni Giovanni , Cataldo Gennaro , Rubegni Pietro
Published: September 2023

Atypical pigmented facial lesions (aPFLs)—including lentigo maligna (LM) and lentigo maligna melanoma (LMM), solar lentigo (SL), pigmented actinic keratosis (PAK), atypical nevi (AN), seborrheic keratosis (SK) and lichen planus‐like keratosis (LPLK)—can exhibit clinical and dermoscopic overlapping features. We aimed to investigate if and how 14 dermoscopic features suggestive for the aforementioned aPFLs vary according to six facial sites among 1197 aPFLs cases (excised to rule out malignancy) along with lesion and patients' metadata. According to distribution and association analysis, aPFLs on the forehead of a male patient aged > 69 years displaying the obliterated follicular openings pattern, appear to be more at risk of malignancy. Of converse, aPFLs of the orbital/cheek/nose area with evident and regular follicular openings with diameter < 10 mm in a female aged below 68 are probably benign. The obliterated follicular openings, keratin plugs, evident and regular follicular openings and target‐like pattern features differed significantly among six facial areas in all aPFLs cases. Lesion of the nose may show both features suggestive of malignancy and benignity (e.g. many SL and PAK may display target‐like pattern and some LM/LMM cases display keratin plugs and evident and follicular openings), making these features less specific.
A consumer cross‐over trial suggests that there are significant seasonal changes of the tensile properties (wet) of human hair
Authors: Wortmann Franz J. , Wortmann Gabriele
Published: September 2023

Objectives

Through the cooperation with an industrial partner, we gained a set of data for the tensile properties (wet) of human hair. The hair samples originated from a cross‐over study with two groups of individuals, using for a topical application sequentially two products (A and B). Each phase of the study lasted 6 months. The phases of the study by chance covered first largely the winter and then the summer period. Initially, tensile variables were chosen, which not only reflect the mechanical properties of hair (modulus, break strain, and break stress) but which are also considered to have a good connection to practice‐relevant hair properties. The initial analysis of the data showed that changes were observed for the variables due to the treatment phases. However, these were either small or difficult to interpret.

Methods

Against this background and using two‐factor analysis of variance, we investigated the hypothesis that the tensile properties of hair (wet) may show significant seasonal changes. For this, we chose those two independent variables, which reflect the properties of the intermediate filaments (modulus) and the matrix (break strain) in the composite structure of the hair cortex.

Results

The results support the ‘seasonal’ hypothesis and clearly show that the variables show significant changes from Winter to Summer (modulus: 10% increase; break strain: 3% decrease). The seasonal effect was thus a major reason, why the first stage of the analysis of the data was inconclusive.

Conclusions

The tensile properties of the main morphological components of the cortex show distinct seasonal changes. Towards the summer, the hair becomes stiffer and more brittle. Furthermore, the results suggest that seasonal effects may need to be taken into account when conducting studies on lengths of hair grown during different seasons.
Reliability and validity of the revised Rushton Moral Resilience Scale for healthcare workers
Authors: Rushton Cynda H. , Hanson Ginger C. , Boyce Danielle , Holtz Heidi , Nelson Katie E. , Spilg Edward G. , Robillard Rébecca
Published: September 2023

Aim

To refine the Rushton Moral Resilience Scale (RMRS) by creating a more concise scale, improving the reliability, particularly of the personal integrity subscale and providing further evidence of validity.

Background

Healthcare workers are exposed to moral adversity in practice. When unable to preserve/restore their integrity, moral suffering ensues. Moral resilience is a resource that may mitigate negative consequences. To better understand mechanisms for doing so, a valid and reliable measurement tool is necessary.

Design

Cross‐sectional survey.

Methods

Participants (N = 1297) had completed ≥1 items on the RMRS as part of the baseline survey of a larger longitudinal study. Item analysis, confirmatory factor analyses, reliability analyses (Cronbach's alpha), and correlations were used to establish reliability and validity of the revised RMRS.

Results

Item and confirmatory factor analysis were used to refine the RMRS from 21 to 16 items. The four‐factor structure (responses to moral adversity, personal integrity, relational integrity and moral efficacy) demonstrated adequate fit in follow‐up confirmatory analyses in the initial and hold‐out sub‐samples. All subscales and the total scale had adequate reliabilities (α ≥ 0.70). A higher‐order factor analysis supports the computation of either subscale scores or a total scale score. Correlations of scores with stress, anxiety, depression and moral distress provide evidence of the scale's validity. Reliability of the personal integrity subscale improved.

Conclusion and Implications

The RMRS‐16 demonstrates adequate reliability and validity, particularly the personal integrity subscale. Moral resilience is an important lever for reducing consequences when confronted with ethical challenges in practice. Improved reliability of the four subscales and having a shorter overall scale allow for targeted application and will facilitate further research and intervention development.

Patient/Public Contribution

Data came from a larger study of Canadian healthcare workers from multiple healthcare organizations who completed a survey about their experiences during COVID‐19.
Treating facial overfilled syndrome with impaired facial expression—Presenting clinical experience with ultrasound imaging
Authors: Schelke Leonie , Harris Steven , Cartier Hugues , Alfertshofer Michael , Doestzada Marwah , Cotofana Sebastian , Velthuis Peter J.
Published: September 2023

Background

Facial overfilled syndrome is an adverse event following minimally invasive soft tissue filler injections. It presents in most cases as excess midfacial volume and/or as unnatural smile which is difficult to detect due to the absence of standardized evaluation methods.

Objective

To showcase how to identify, evaluate, and treat facial overfilled syndrome by utilizing facial ultrasound and simultaneous hyaluronidase injections.

Methods

Twenty‐eight consecutive patients (26 females, 2 males) were enrolled in this study in which facial ultrasound was performed to evaluate the location previously implanted filler material. The position of the oral commissure was objectively measured in relation to bony landmarks, and the severity of lateral canthal lines was assessed by independent and blinded raters.

Results

The material was identified in 35.7% inside the subdermal fatty layer, in 28.6% inside the deep supra‐periosteal fatty layer, in 10.7% inside the fibrous layer deep to the subdermal fatty layer, whereas in 25.0%, the product was not possible to locate clearly inside one specific layer. On average, 81.6 I.U. [range: 75–150] of hyaluronidase were injected. Lateral canthal line severity was before the treatment 2.28 (1.4) and was after the hyaluronidase treatment 2.02 (1.3) with p = 0.578. The position of the oral commissure increased by 0.60 cm in vertical and by 0.30 cm in horizontal directions (both p < 0.001).

Conclusion

Facial overfilled syndrome following aesthetic soft tissue filler injections can present as excess midfacial volume but also as unnatural smile. Targeted hyaluronidase injections into the culprit pockets inside the midfacial soft tissues have shown to re‐establish a natural smile, to reduce excess midfacial volume, and to decrease lateral canthal line severity.
Severe neonatal birth injury: Observational study of associations with operative, cesarean, and spontaneous vaginal delivery
Authors: Auger Nathalie , Wei Shu Qin , Ayoub Aimina , Luu Thuy Mai
Published: September 2023

Aim

To determine the association of successful and unsuccessful operative vaginal delivery attempts with risk of severe neonatal birth injury.

Methods

We conducted a population‐based observational study of 1 080 503 births between 2006 and 2019 in Quebec, Canada. The main exposure was operative vaginal delivery with forceps or vacuum, elective or emergency cesarean with or without an operative vaginal attempt, and spontaneous delivery. The outcome was severe birth injury, including intracranial hemorrhage, brain and spinal damage, Erb's paralysis and other brachial plexus injuries, epicranial subaponeurotic hemorrhage, skull and long bone fractures, and liver, spleen, and other neonatal body injuries. We determined the association of delivery mode with risk of severe birth injury using adjusted risk ratios (RR) and 95% confidence intervals (CI).

Results

A total of 8194 infants (0.8%) had severe birth injuries. Compared with spontaneous delivery, vacuum (RR 2.98, 95% CI 2.80–3.16) and forceps (RR 3.35, 95% CI 3.07–3.66) were both associated with risk of severe injury. Forceps was associated with intracranial hemorrhage (RR 16.4, 95% CI 10.1–26.6) and brain and spinal damage (RR 13.5, 95% CI 5.72–32.0), while vacuum was associated with epicranial subaponeurotic hemorrhage (RR 27.5, 95% CI 20.8–36.4) and skull fractures (RR 2.04, 95% CI 1.86–2.25). Emergency cesarean after an unsuccessful operative attempt was associated with intracranial and epicranial subaponeurotic hemorrhage, but elective and other emergency cesareans were not associated with severe injury.

Conclusions

Operative vaginal delivery and unsuccessful operative attempts that result in an emergency cesarean are associated with elevated risks of severe birth injury.