bluuebunny/crossref_metadata_2025 huggingface dataset:
SWIP mediates retromer-independent membrane recruitment of the WASH complex
Authors: Dostál V. , Humhalová T. , Beránková P. , Pácalt O. , Libusová L.
Published: August 2022

The pentameric WASH complex facilitates endosomal protein sorting by activating Arp2/3, which in turn leads to the formation of F-actin patches specifically on the endosomal surface. It is generally accepted that WASH complex attaches to the endosomal membrane via the interaction of its subunit FAM21 with the retromer subunit VPS35. However, we observe the WASH complex and F-actin present on endosomes even in the absence of VPS35. We show that the WASH complex binds to the endosomal surface in both a retromer-dependent and a retromer-independent manner. The retromer-independent membrane anchor is directly mediated by the subunit SWIP. Furthermore, SWIP can interact with a number of phosphoinositide species. Of those, our data suggest that the interaction with phosphatidylinositol-3,5-bisphosphate (PI(3,5)P2) is crucial to the endosomal binding of SWIP. Overall, this study reveals a new role of the WASH complex subunit SWIP and highlights the WASH complex as an independent, self-sufficient trafficking regulator.

Dostál et al. contradict the prevailing concept that WASH complex is principally recruited to the endosome via its interaction with the retromer. They show that the WASH complex binds to the endosomal membrane via its subunit SWIP, and this interaction can be prevented by removing phosphatidylinositol-3,5-bisphosphate from cells.
L-type calcium channels link oxidative stress to calcium signaling pathway and membrane excitability: Insights from computational modeling of dopaminergic neurons
Authors: Andres M.A. , Karratti-Abordo S. , Bryan C. , Shoji A. , Zaporteza M. , Castelfranco A.M.
Published: August 2022

Dopamine neurons, which are critical in movement, cognition, and reward learning, are vulnerable to oxidative stress during aging, drugs of abuse, and viral infection and can lead to neurodegeneration. Previous work used computational modeling to study dopamine neuron function based on experimental findings from rodent brain slices containing dopamine neurons. Here we show for the first time the feasibility and utility of applying such computational models of DA neurons to the analysis of experimental findings from in-vitro cultured cells. We used DCFH-DA (and DHE) and time-lapse, Fura-2 ratiometric imaging to measure changes in ROS levels and changes in intracellular calcium (Ca2+) levels, respectively, in two dopaminergic cell models: differentiated SH-SY5Y and differentiated human neural progenitor cells. We investigated how peroxide-dependent changes in the behavior of the L-type channel might alter the excitability of the dopaminergic cell. We found that L-type channels mediated clusters of calcium spikes (or oscillations) and that our model suggested that such increased excitability could be explained by changes in the voltage-dependence of activation of the L-type channels in response to exogenous peroxide. Our findings suggested that L-type channels link oxidative stress responses to modulation of excitability. We conclude that the Ca2+channel blocker nicardipine may help disrupt this link by reducing oxidative stress and preventing channel activation at more hyperpolarized potentials, thus reducing plasma membrane excitability.
Spatio-Temporal Dynamics of Oscillatory Brain Activity during the Observation of Actions and Interactions between Point-light Agents
Authors: Friedrich Elisabeth V. C. , Zillekens Imme C. , Biel Anna Lena , O’Leary Dariusz , Singer Johannes , Seegenschmiedt Eva Victoria , Sauseng Paul , Schilbach Leonhard
Published: August 2022

Predicting actions from nonverbal cues and using them to optimize one’s response behavior (i.e., interpersonal predictive coding) is essential in everyday social interactions. We aimed to investigate the neural correlates of different cognitive processes evolving over time during interpersonal predictive coding. Thirty-nine participants watched two agents depicted by moving point-light stimuli while an electroencephalogram (EEG) was recorded. One well-recognizable agent performed either a ‘communicative’ or an ‘individual’ action. The second agent either was blended into a cluster of noise dots (i.e., present), or was entirely replaced by noise dots (i.e., absent), which participants had to differentiate. EEG amplitude and coherence analyses for theta, alpha and beta frequency bands revealed a dynamic pattern unfolding over time: Watching communicative actions was associated with enhanced coupling within medial anterior regions involved in social and mentalizing processes and with dorsolateral prefrontal activation indicating a higher deployment of cognitive resources. Trying to detect the agent in the cluster of noise dots without having seen communicative cues was related to enhanced coupling in posterior regions for social perception and visual processing. Observing an expected outcome was modulated by motor system activation. Finally, when the agent was detected correctly, activation in posterior areas for visual processing of socially-relevant features was increased. Taken together, our results demonstrate that it is crucial to consider the temporal dynamics of social interactions and of their neural correlates to better understand interpersonal predictive coding. This could lead to optimized treatment approaches for individuals with problems in social interactions.
Target-matched increased fidelity SpCas9 variants can edit any target without genome-wide off-target effects
Authors: Kulcsár Péter István , Tálas András , Ligeti Zoltán , Tóth Eszter , Rakvács Zsófia , Végi Vanessza Laura , Krausz Sarah Laura , Huszár Krisztina , Welker Ervin
Published: August 2022

Streptococcus pyogenes Cas9 (SpCas9) has been employed as a genome engineering tool with a promising potential within therapeutics. However, its off- target effects pose a major limitation for applications requiring high specificity. Approaches developed to date to mitigate this effect, including any of the increased fidelity (i.e., high-fidelity) SpCas9 variants, only provide efficient editing on a relatively small fraction of targets without detectable off-targets. Upon addressing this problem, we have revealed a rather unexpected cleavability ranking of target sequences, and a cleavage rule that governs the on-target and off-target cleavage of increased fidelity SpCas9 variants but not that of SpCas9-NG or xCas9. As a consequence of this rule, each target needs a matching-fidelity, optimal variant for efficient cleavage without detectable off-target effects. By exploiting this finding, we have developed an extended set of increased fidelity variants spanning across a wide range, with differences in fidelity small enough to comprise an optimal variant for any target, irrespective of its cleavability ranking. We have demonstrated efficient editing with maximum specificity even on those targets that have been challenged but failed in previous studies.
Piezo1 mechanosensing regulates integrin-dependent chemotactic migration in human T cells
Authors: Liu Chinky Shiu Chen , Mandal Tithi , Biswas Parijat , Hoque Md. Asmaul , Bandopadhyay Purbita , Sinha Bishnu Prasad , Sarif Jafar , D’Rozario Ranit , Sinha Deepak Kumar , Sinha Bidisha , Ganguly Dipyaman
Published: August 2022

T cells are crucial for efficient antigen-specific immune responses and thus their migration within the body, to inflamed tissues from circulating blood or to secondary lymphoid organs, play a very critical role. T cell extravasation in inflamed tissues depends on chemotactic cues and interaction between endothelial adhesion molecules and cellular integrins. A migrating T cell is expected to sense diverse external and membrane-intrinsic mechano-physical cues, but molecular mechanisms of such mechanosensing in cell migration are not established. We explored if the professional mechanosensor Piezo1 play any role during integrin-dependent chemotaxis of human T cells. We found that deficiency of Piezo1 in human T cells interfered with integrin-dependent cellular motility on ICAM-1-coated surface. Piezo1 recruitment at the leading edge of moving T cells is dependent on and follows focal adhesion formation at the leading edge and local increase in membrane tension on chemokine receptor activation. Piezo1 recruitment and activation, followed by calcium influx and calpain activation, in turn are crucial for the integrin LFA-1 (CD11a/CD18) recruitment at the leading edge of the chemotactic human T cells. Thus, we find that Piezo1 activation in response to local mechanical cues constitutes a membrane-intrinsic component of the ‘outside-in’ signaling in human T cells, migrating in response to chemokines, that mediates integrin recruitment to the leading edge.
Intrahost SARS-CoV-2 k-mer identification method (iSKIM) for rapid detection of mutations of concern reveals emergence of global mutation patterns
Authors: Thommana Ashley , Shakya Migun , Gandhi Jaykumar , Fung Christian K. , Chain Patrick S.G. , Berry Irina Maljkovic , Conte Matthew A.
Published: August 2022

Despite unprecedented global sequencing and surveillance of SARS-CoV-2, timely identification of the emergence and spread of novel variants of concern (VoCs) remains a challenge. Several million raw genome sequencing runs are now publicly available. We sought to survey these datasets for intrahost variation to study emerging mutations of concern. We developed iSKIM (“intrahost SARS-CoV-2 k-mer identification method”) to relatively quickly and efficiently screen the many SARS-CoV-2 datasets to identify intrahost mutations belonging to lineages of concern. Certain mutations surged in frequency as intrahost minor variants just prior to, or while lineages of concern arose. The Spike N501Y change common to several VoCs was found as a minor variant in 834 samples as early as October 2020. This coincides with the timing of the first detected samples with this mutation in the Alpha/B.1.1.7 and Beta/B.1.351 lineages. Using iSKIM, we also found that Spike L452R was detected as an intrahost minor variant as early as September 2020, prior to the observed rise of the Epsilon/B.1.429/B.1.427 lineages in late 2020. iSKIM rapidly screens for mutations of interest in raw data, prior to genome assembly, and can be used to detect increases in intrahost variants, potentially providing an early indication of novel variant spread.
Are family firms really reluctant to innovate? Evidence from IPOs
Authors: Ossorio Mario
Published: August 2022

Purpose

The aim of this paper is to explore the family firms' propensity to undertake R&D investments after going public, showing how it varies due to the ownership structure.

Design/methodology/approach

The analysis is based on a sample of 132 French and Italian family and nonfamily IPOs in the period 2013–2018.

Findings

The empirical findings show a positive relationship between the quantity of post-IPO shares retained by family owners and R&D investments. Furthermore, the abovementioned relationship is negatively affected by the generational stage and positively by the presence of a lone founder.

Practical implications

Outside investors of family firms may be assured in buying shares of founding family firms after going public because they are stimulated to undertake R&D investments and therefore create overall value in the long term. Furthermore, external managers of lone-founder and first-generation family firms can adopt innovation investments without fear of being replaced as a consequence of a hostile takeover. Lastly, private equity should support later generation family IPOs, providing them with capital and managerial skills in order to generate value for shareholders.

Originality/value

Past studies have mostly shown family firms' reluctance to undertake R&D investments; however, scholars have focused on private or public family firms, ruling out the analysis of family firms' innovation behaviour within the setting of an IPO. To the best of the author's knowledge, this study represents the first empirical attempt to investigate the relationship between family firms and post-IPO innovation investments, when the capital infusion relaxes the financial constraints of family firms.
Partial least squares as a tool for scientific inquiry: comments on Cadogan and Lee
Authors: Henseler Jörg , Schuberth Florian
Published: August 2022

Purpose

In their paper titled “A Miracle of Measurement or Accidental Constructivism? How PLS Subverts the Realist Search for Truth,” Cadogan and Lee (2022) cast serious doubt on PLS’s suitability for scientific studies. The purpose of this commentary is to discuss the claims of Cadogan and Lee, correct some inaccuracies, and derive recommendations for researchers using structural equation models.

Design/methodology/approach

This paper uses scenario analysis to show which estimators are appropriate for reflective measurement models and composite models, and formulates the statistical model that underlies PLS Mode A. It also contrasts two different perspectives: PLS as an estimator for structural equation models vs. PLS-SEM as an overarching framework with a sui generis logic.

Findings

There are different variants of PLS, which include PLS, consistent PLS, PLSe1, PLSe2, proposed ordinal PLS and robust PLS, each of which serves a particular purpose. All of these are appropriate for scientific inquiry if applied properly. It is not PLS that subverts the realist search for truth, but some proponents of a framework called “PLS-SEM.” These proponents redefine the term “reflective measurement,” argue against the assessment of model fit and suggest that researchers could obtain “confirmation” for their model.

Research limitations/implications

Researchers should be more conscious, open and respectful regarding different research paradigms.

Practical implications

Researchers should select a statistical model that adequately represents their theory, not necessarily a common factor model, and formulate their model explicitly. Particularly for instrumentalists, pragmatists and constructivists, the composite model appears promising. Researchers should be concerned about their estimator’s properties, not about whether it is called “PLS.” Further, researchers should critically evaluate their model, not seek confirmation or blindly believe in its value.

Originality/value

This paper critically appraises Cadogan and Lee (2022) and reminds researchers who wish to use structural equation modeling, particularly PLS, for their statistical analysis, of some important scientific principles.
Pre-owned fashion as sustainable consumerism? Opportunities and challenges in the Vietnam market
Authors: Hong Lan Lam , Watkins Jerry
Published: August 2022

Purpose

The purpose of this paper is to identify opportunities and challenges for small- to medium-sized pre-owned fashion enterprises (SMEs) in Vietnam. While recent studies have identified the growth of pre-owned fashion in developed economies, pre-owned clothing remains negatively associated by some consumers with overseas charity donations of second-hand clothes to Vietnam, following the economic upheaval of the 1980s.

Design/methodology/approach

Qualitative data were collected via semi-structured in-depth interviews with founders and/or owners of pre-owned fashion SMEs (n = 5, aged 25–40 years) with physical stores located in Ho Chi Minh City alongside online retail platforms. All interviewees are significant industry and consumer influencers.

Findings

Younger Vietnamese consumers are motivated by (1) pre-owned fashion's value for money compared to buying new western branded luxury items and (2) the ability of pre-owned and vintage fashion to allow the wearer to create a unique personal style. While Vietnamese consumers and retailers associate “sustainable fashion” with various, often unrelated concepts, the impact of global and local discourse around sustainable fashion in the last five years has generally supported wider interest in pre-owned fashion.

Originality/value

This study contributes to the relatively modest pool of English-language research on the fashion and textiles industry in Vietnam, a global fast-fashion manufacturing hub. The findings advance understanding of how pre-owned fashion is growing as a high-end niche market despite significant supply chain restrictions as well as a lingering perception of pre-owned fashion as charitable donations.
The impacts of knowledge-oriented leadership on employees' knowledge management behaviors in Chinese based organizations: a qualitative study
Authors: Liu Yi , Zheng Haitao , Ghosh Koustab , Zheng Yaozhou , Liu Chao
Published: August 2022

Purpose

This study aims to minimize the research gap by finding out what are the current state of knowledge management (KM) in the Chinese private science and technology organizations, the essential factors for promoting KM behaviors and the role of knowledge-oriented leadership in determining employees’ KM behaviors. Specifically, this research attempts to create a theoretical framework, which can be used to facilitate KM implementation in general, in the Chinese context in particular.

Design/methodology/approach

Semi-structured interviews with executives, senior managers and specialists were used to capture interviewees’ responses to the research question. The responses were analyzed with Nvivo to detect the obstacles of KM behaviors within Chinese private science and technology organizations.

Findings

This study highlights that poor KM behaviors are caused by knowledge-oriented leaders’ weak awareness of the KM values, and also these leaders are not equipped with the necessary knowledge-oriented leadership skills. As a result, there is a lack of knowledge sharing and knowledge inheritance. To respond to the identified KM related issues, while maximizing the KM values, some effective countermeasures focusing on the strategic, managerial as well as operational levels are proposed.

Practical implications

There is a need for knowledge-oriented leaders to recognize the growing significance of KM practices, and to increase the level of awareness of KM values. To achieve such ambition, they need to build a corporate knowledge culture, which promotes knowledge development, application, preservation, sharing and inheritance.

Originality/value

This study contributes to deepening the understandings of the linkage between knowledge-oriented leadership and KM behaviors, which is of great significance to promote the soft power of KM on employees’ attitudes and behaviors.
Capecitabine and temozolomide (CAPTEM) is effective in metastatic well‐differentiated gastrointestinal neuroendocrine tumors
Authors: Dogan Izzet , Tastekin Didem , Karabulut Senem , Sakar Burak
Published: August 2022

Objective

The aim of this study was to investigate the outcomes and prognostic factors of patients with metastatic gastrointestinal neuroendocrine tumor (mGI‐NET) who were treated with capecitabine and temozolomide (CAPTEM) and somatostatin receptor ligand (octreotide or lanreotide).

Methods

Clinicopathological characteristics and treatment outcomes of 43 patients with mGI‐NET were retrospectively evaluated. Overall survival (OS) and progression‐free survival (PFS) were evaluated using Kaplan–Meier curve. Cox‐regression analysis was used to assess prognostic variables.

Results

There were 23 (53.5%) men and 20 women (46.5%) with a median age of 59 years (range 27–85 y). Patients were given octreotide (86.0%) or lanreotide (14.0%) with CAPTEM. In patients with well‐differentiated mGI‐NET, median PFS was 17.4 months, and the disease control rate was 71.1%. Patients with poorly differentiated mGI‐NET showed no response, and the median PFS was 4.5 months. Four (9.3%) discontinued the medication due to toxicity. Anemia (37.2%), thrombocytopenia (25.6%), and fatigue (16.3%) were the most prevalent adverse events. The 5‐year OS rate was 61.0% in all patients during a median follow‐up of 33.8 months. In multivariate analysis, age (P = 0.014) and tumor differentiation (P < 0.001) were statistically significant factors for OS.

Conclusions

CAPTEM plus somatostatin receptor ligands were efficacious and well tolerated in individuals with well‐differentiated mGI‐NET. However, it was ineffective for those with poorly differentiated tumors. Age of 60 years or elder and poorly differentiated tumors were related to a poor patient prognosis.
Toward an ontology of tobacco, nicotine and vaping products
Authors: Cox Sharon , West Robert , Notley Caitlin , Soar Kirstie , Hastings Janna
Published: August 2022

Background and aims

Ontologies are ways of representing information that improve clarity and the ability to connect different data sources. This paper proposes an initial version of an ontology of tobacco, nicotine and vaping products with the aim of reducing ambiguity and confusion in the field.

Methods

Terms related to tobacco, nicotine and vaping products were identified in the research literature and their usage characterised. Basic Formal Ontology was used as a unifying upper‐level ontology to describe the domain, and classes with definitions and labels were developed linking them to this ontology. Labels, definitions and properties were reviewed and revised in an iterative manner until a coherent set of classes was agreed by the authors.

Results

Overlapping, but distinct classes were developed: ‘tobacco‐containing product’, ‘nicotine‐containing product’ and ‘vaping device’. Subclasses of tobacco‐containing products are ‘combustible tobacco‐containing product’, ‘heated tobacco product’ and ‘smokeless tobacco‐containing product’. Subclasses of combustible tobacco‐containing product include ‘cigar’, ‘cigarillo’, ‘bidi’ and ‘cigarette’ with further subclasses including ‘manufactured cigarette’. Manufactured cigarettes have properties that include ‘machine‐smoked nicotine yield’ and ‘machine‐smoked tar yield’. Subclasses of smokeless tobacco product include ‘nasal snuff’, ‘chewing tobacco product’, and ‘oral snuff’ with its subclass ‘snus’. Subclasses of nicotine‐containing product include ‘nicotine lozenge’ and ‘nicotine transdermal patch’. Subclasses of vaping device included ‘electronic vaping device’ with a further subclass, ‘e‐cigarette’. E‐cigarettes have evolved with a complex range of properties including atomiser resistance, battery power, properties of consumables including e‐liquid nicotine concentration and flavourings, and the ontology characterises classes of product accordingly.

Conclusions

Use of an ontology of tobacco, nicotine and vaping products should help reduce ambiguity and confusion in tobacco control research and practice.
Durable scalable 3D SLA‐printed cuff electrodes with high performance carbon + PEDOT:PSS‐based contacts
Authors: Doering Onna Marie , Vetter Christian , Alhawwash Awadh , Horn M. Ryne , Yoshida Ken
Published: August 2022

Background

The stimulation and recording performance of implanted neural interfaces are functions of the physical and electrical characteristics of the neural interface, its electrode material and structure. Therefore, rapid optimization of such characteristics is becoming critical in most clinical and research studies. This paper describes the development of an upgraded 3D printed cuff electrode shell design containing a novel intrinsically conductive polymer (ICP) for stimulation and recording of peripheral nerve fibers.

Methods

A 3D stereolithography (SLA) printer was used to print a scalable, custom designed, C‐cuff electrode and I‐beam closure for accurate, rapid implementation. A novel contact consisting of a percolated carbon graphite base electrodeposited with an intrinsically conductive polymer (ICP), poly(3,4‐ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) produced a PEDOT:PSS + carbon black (CB) matrix that was used to form the electrochemical interface on the structure. Prototype device performance was tested both in‐vitro and in‐vivo for electrical chemical capacity, electrochemical interfacial impedance, surgical handling, and implantability. The in‐vivo work was performed on the sciatic nerve of 25 anesthetized Sprague Dawley rats to demonstrate recording and stimulating ability.

Results

Prototypes of different spatial geometries and number of contacts (bipolar, tripolar, and tetrapolar) were designed. The design was successfully printed with inner diameters down to 500 μm. Standard bipolar and tripolar cuffs, with a 1.3 mm inner diameter (ID), 0.5 mm contact width, 1.0 mm pitch, and a 1.5 mm end distance were used for the functional tests. This geometry was appropriate for placement on the rat sciatic nerve and enabled in‐vivo testing in anesthetized rats. The contacts on the standard bipolar electrode had an area of 2.1 × 10−2 cm2. Cyclic voltammetry on ICP coated and uncoated graphite contacts showed that the ICP increased the average charge storage capacity (CSC) by a factor of 30. The corresponding impedance at 1 Hz was slightly above 1 kΩ, a 99.99% decrease from 100 kΩ in the uncoated state. The statistical comparison of the pre‐ versus post‐stimulation impedance measurements were not significantly different (p‐value > 0.05).

Conclusions

The new cuff electrode enables rapid development of cost‐effective functional stimulation devices targeting nerve bundles less than 1.0 mm in diameter. This allows for recording and modulation of a low‐frequency current targeted within the peripheral nervous system.
An empirical perspective on moral expertise: Evidence from a global study of philosophers
Authors: Niv Yarden , Sulitzeanu‐Kenan Raanan
Published: August 2022

Considerable attention in bioethics has been devoted to moral expertise and its implications for handling applied moral problems. The existence and nature of moral expertise has been a contested topic, and particularly, whether philosophers are moral experts. In this study, we put the question of philosophers’ moral expertise in a wider context, utilizing a novel and global study among 4,087 philosophers from 96 countries. We find that despite the skepticism in recent literature, the vast majority of philosophers do believe in moral expertise and in the contribution of philosophical training and experience to its acquisition. Yet, they still differ on what philosophers’ moral expertise consists of. While they widely accept that philosophers possess superior analytic abilities regarding moral matters, they diverge on whether they also possess improved ability to judge moral problems. Nonetheless, most philosophers in our sample believe that philosophers possess an improved ability to both analyze and judge moral problems and that they commonly see these two capacities as going hand in hand. We also point at significant associations between personal and professional attributes and philosophers’ beliefs, such as age, working in the field of moral philosophy, public involvement, and association with the analytic tradition. We discuss the implications of these findings for the debate about moral expertise.
Dynamics of initial carbon allocation after drought release in mature Norway spruce—Increased belowground allocation of current photoassimilates covers only half of the carbon used for fine‐root growth
Authors: Hikino Kyohsuke , Danzberger Jasmin , Riedel Vincent P. , Hesse Benjamin D. , Hafner Benjamin D. , Gebhardt Timo , Rehschuh Romy , Ruehr Nadine K. , Brunn Melanie , Bauerle Taryn L. , Landhäusser Simon M. , Lehmann Marco M. , Rötzer Thomas , Pretzsch Hans , Buegger Franz , Weikl Fabian , Pritsch Karin , Grams Thorsten E. E.
Published: August 2022

After drought events, tree recovery depends on sufficient carbon (C) allocation to the sink organs. The present study aimed to elucidate dynamics of tree‐level C sink activity and allocation of recent photoassimilates (Cnew) and stored C in c. 70‐year‐old Norway spruce (Picea abies) trees during a 4‐week period after drought release. We conducted a continuous, whole‐tree 13C labeling in parallel with controlled watering after 5 years of experimental summer drought. The fate of Cnew to growth and CO2 efflux was tracked along branches, stems, coarse‐ and fine roots, ectomycorrhizae and root exudates to soil CO2 efflux after drought release. Compared with control trees, drought recovering trees showed an overall 6% lower C sink activity and 19% less allocation of Cnew to aboveground sinks, indicating a low priority for aboveground sinks during recovery. In contrast, fine‐root growth in recovering trees was seven times greater than that of controls. However, only half of the C used for new fine‐root growth was comprised of Cnew while the other half was supplied by stored C. For drought recovery of mature spruce trees, in addition to Cnew, stored C appears to be critical for the regeneration of the fine‐root system and the associated water uptake capacity.
Outcomes of extensive stage extrapulmonary small cell cancer
Authors: Gandy Geovanny , Yip Po Yee , Tognela Annette , Hayat Faisal , Fox William , Kok Peey Sei
Published: August 2022

Background

Extrapulmonary small cell cancer (EPSCC) is a rare malignancy with an incidence of approximately 0.1%–0.4% of all cancers. Treatment of this disease is often based on small cell lung cancer.

Aims

We aimed to investigate real‐world clinical outcomes of patients with extensive‐stage (ES) ESPCC.

Methods

Patients diagnosed with ES EPSCC between 2010 and 2020 from multiple centres in New South Wales were identified. Patient, disease and treatment characteristics were collected and presented using descriptive statistics. Survival was analysed using the Kaplan–Meier method. Univariate and multivariate Cox regression hazard models were used to identify potential prognostic factors.

Results

Sixty eligible ES EPSCC patients were identified, including 65% male and 35% female. The mean age was 69 years (range 37–88). Forty‐five per cent were never smokers, 42% ex‐smokers and 13% current smokers, and 17% of patients had limited‐stage disease prior to development of ES disease. The most common primary sites were genitourinary (42%; mainly prostate (n = 14) and bladder (n = 10)), gastrointestinal (28%; mainly oesophagus (n = 5) and colon (n = 4)) and unknown primary (22%). Treatments received included palliative chemotherapy (67%), palliative radiotherapy (53%), palliative surgery (13%) and best supportive care alone (13%). The median overall survival (OS) was 8.0 months. The median progression‐free survival was 5.4 months, and response rate to first‐line chemotherapy was 65%. Platinum‐based chemotherapy was prognostic of longer OS (HR 0.27, CI 0.12–0.60, P = 0.001).

Conclusions

Patients with ES EPSCC had good response to palliative chemotherapy, but OS remained poor. Further research is required to improve the prognosis in this population.
Validation of an electrocardiographic marker of low voltage areas in the right ventricular outflow tract in patients with idiopathic ventricular arrhythmias
Authors: Parreira Leonor , Marinheiro Rita , Carmo Pedro , Chambel Duarte , Mesquita Dinis , Amador Pedro , Marques Lia , Mancelos Sofia , Reis Roberto Palma , Adragao Pedro
Published: August 2022

Background

Previous studies have reported the presence of subtle abnormalities in the right ventricular outflow tract (RVOT) in patients with apparently normal hearts and ventricular arrhythmias (VAs) from the RVOT, including the presence of low voltage areas (LVAs). This LVAs seem to be associated with the presence of ST‐segment elevation in V1 or V2 leads at the level of the 2nd intercostal space (ICS).

Objective

Our aim was to validate an electrocardiographic marker of LVAs in the RVOT in patients with idiopathic outflow tract VAs.

Methods

A total of 120 patients were studied, 84 patients referred for ablation of idiopathic VAs with an inferior axis by the same operator, and a control group of 36 patients without VAs. Structural heart disease including arrhythmogenic right ventricular cardiomyopathy was ruled out in all patients. An electrocardiogram was performed with V1–V2 at the 2nd ICS, and ST‐segment elevation ≥1 mm and T‐wave inversion beyond V1 were assessed. Bipolar voltage map of the RVOT was performed in sinus rhythm (0.5–1.5 mV color display). Areas with electrograms <1.5 mV were considered LVAs, and their presence was assessed. We compared three groups, VAs from the RVOT (n = 66), VAs from the LVOT (n = 18) and Control group (n = 36). ST‐elevation, T‐wave inversion and left versus right side of the VAs were tested as predictors of LVAs, respective odds ratio (ORs) (95% confidence interval [CI]) and p values, were calculated with univariate logist regression. Variables with a p < .005 were included in the multivariate analysis.

Results

ST‐segment elevation, T‐wave inversion and LVAs were present in the RVOT group, LVOT group and Control group as follows: (62%, 17%, and 6%, p < .0001), (33%, 29%, and 0%, p = .001) and (62%, 25%, and 14%, p < .0001). The ST‐segment elevation, T‐wave inversion and right‐sided VAs were all predictors of LVAs, respective unadjusted ORs (95% CI), p values were, 32.31 (11.33–92.13), p < .0001, 4.137 (1.615–10.60), p = .003 and 8.200 (3.309–20.32), p < .0001. After adjustment, the only independent predictor of LVAs was the ST‐segment elevation, with an adjusted OR (95% CI) of 20.94 (6.787–64.61), p < .0001.

Conclusion

LVAs were frequently present in patients with idiopathic VAs. ST‐segment elevation was the only independent predictor of their presence.
Construct validity and psychometric properties of the Chinese version of the City Birth Trauma Scale
Authors: Nie Xiao‐Fei , Cheng Li , Huang Fei , Zhang Tao‐Tao , Yao Yin‐Di , Tan Jing , Ke Yu‐Ye
Published: August 2022

Background

Currently, most postpartum posttraumatic stress disorder (PTSD) screening scales used in China are general PTSD scales which are not compiled specifically for pregnant women and thus cannot reflect the unique needs of this population. This study aimed to translate the City Birth Trauma Scale (City BiTS) into Chinese and validate its psychometric characteristics in Chinese postpartum women.

Methods

After translation, back‐translation, and expert discussion, 596 mothers at 1 to 12 months postpartum filled out the questionnaires through the Internet. The reliability and validity of the translated questionnaire were tested.

Results

The Cronbach's α coefficient of the Chinese version of City BiTS (City BiTS‐C) was 0.889, the test–retest reliability was 0.86, and the content validity was 0.93. Exploratory factor analysis extracted two factors accounted for 63.148% of the variance. The City BiTS‐C had appropriate construct validity in the Chinese culture (root mean square error of approximation [RMSEA] = 0.048, <0.05; χ2/df = 2.666, <3). The values of the incremental fit index (IFI) and the Tucker‐Lewis coefficient (TLI) were 0.990 and 0.976, which identified that the model was a good fit for the data. The values of the comparative fit index (CFI) and the normed fit index (NFI) were 0.890 and 0.873, respectively.

Conclusions

The City BiTS‐C is a reliable and valid measure to screening and diagnosis the postpartum PTSD among new mothers who gave birth in the past year in mainland China.

Implications

The City BiTS‐C is a short, reliable, and valid instrument that measures the symptoms of postpartum PTSD, and it is recommend for clinical screening.
Return to Learn ECHO: Telementoring for School Personnel to Help Children Return to School and Learning After Mild Traumatic Brain Injury
Authors: McAvoy Karen , Halstead Mark , Radecki Linda , Shah Amy , Emanuel Anjie , Domain Stephanie , Daugherty Jill , Waltzman Dana
Published: August 2022

BACKGROUND

Return to learn (RTL) after mild traumatic brain injury (mTBI) presents unique challenges for school professionals. A multidisciplinary team approach is necessary yet training school professionals is logistically difficult. This paper describes an innovative pilot RTL program and its evaluation.

METHODS

Utilizing the telehealth/telementoring program Project ECHO® (Extension for Community Healthcare Outcomes), this study utilized a multidisciplinary team of subject matter experts to deliver five 1‐hour sessions across 5 cohorts of school‐based professionals (total of 133 participants). The evaluation used a mixed‐methods approach of post‐session and post‐program participant surveys and post‐program participant focus groups.

RESULTS

Participants who completed a post‐program survey reported statistically significant improvements in essential aspects of RTL knowledge and self‐efficacy. This included improvements in how to manage a student with an mTBI (44.8% to 86.9%), benefits of early return to school for students following mTBI (31.8% to 86.9%), and the importance of written RTL policies/procedures (55.1% to 97.1%).

CONCLUSIONS

This study demonstrates that RTL training via a telementoring approach may be a positive and effective way to train school‐based professionals and improve knowledge and self‐efficacy, especially when attending face‐to‐face trainings are difficult. This model has the potential to produce programmatic and systematic improvements for RTL education.
Unloading of occlusal force aggravates alveolar bone loss in periodontitis
Authors: Zhu Rui , Zhang Zihan , Lu Boyao , Zhang Peng , Liu Weiqing , Liang Xing
Published: August 2022

Background and Objective

Periodontitis (PD), a chronic infectious inflammatory disease initiated by bacteria, is associated with several local contributing factors including occlusal trauma. Previous studies have found that the traumatic occlusal force could aggravate alveolar bone loss during PD. However, the effect of reduced occlusal force during PD remains unclear. This study aimed to explore the effect of occlusal force unloading on PD onset and progression and its underlying mechanism as an effort to provide restoration suggestions for PD patients with dentition defect in clinic. This study might also propose occlusal force unloading could be a new local contributing factor for PD.

Materials and Methods

C57BL/6 mice were used to establish a PD model by the ligation of 5–0 silk around the mandibular left first molar (PD group) and an unloading experiment model by the extraction of their left maxillary first molar (EX group). The THP‐1‐derived macrophages were used to verify in vivo results.

Results

Micro‐CT scanning and H&E staining results consistently showed that PD + EX group experienced the most severe alveolar bone resorption as compared to PD group and control group. Further RNA‐sequencing analysis suggested that occlusal force unloading significantly enhanced osteoclastic resorption, inhibited osteoblastic activity, and promotes M1 and M2 macrophages polarization. Immunofluorescence staining (IF) results showed that compared with the PD group, PD + EX group significantly increased the ratio of M1/M2 polarization. Similar results were observed by RT‐qPCR and IF in vitro: removal of compressive force led to an increased ratio of M1/M2 polarization in LPS‐stimulated THP‐1‐derived macrophages.

Conclusions

Our study demonstrated that occlusal force unloading aggravates bone resorption by increasing the ratio of M1/M2 macrophages polarization during PD, suggesting a previously unknown local contributing factor for PD, and providing a novel insight for dentists to restore missing teeth as an effort to maintain remaining dentition.
Genetic drift drives rapid speciation of an Arctic insular endemic shrew (Sorex pribilofensis)
Authors: Wiens Ben J. , Combe Fraser J. , Dickerson Bobette , Divine Lauren M. , Padula Veronica M. , Sage George K. , Talbot Sandra L. , Hope Andrew G.
Published: August 2022

Episodes of Quaternary environmental change shaped the genomes of extant species, influencing their response to contemporary environments, which are changing rapidly. Island endemics are among the most vulnerable to such change, accounting for a disproportionate number of recent extinctions. To prevent extinctions and conserve island biodiversity it is vital to combine knowledge of species' ecologies with their complex evolutionary histories. The Bering Sea has a history of cyclical island isolation and reconnection, coupled with modern rates of climate change that exceed global averages. The endangered Pribilof Island shrew (Sorex pribilofensis) is endemic to St. Paul Island, Alaska, which was isolated from mainland Beringia ~14,000 years ago by rising sea levels. Using ~11,000 single nucleotide polymorphisms, 17 microsatellites and mitochondrial sequence data, we test predictions about the evolutionary processes driving shrew speciation across Beringia. Our data show considerable differentiation of S. pribilofensis from mainland sibling species, relative to levels of divergence between mainland shrews. We also find a genome‐wide loss of diversity and extremely low Ne for S. pribilofensis. We then show that intraspecific genetic diversity is significantly related to interspecific divergence, and that differentiation between S. pribilofensis and other Beringian shrews is highest across loci that are fixed in S. pribilofensis, indicating that strong drift has driven differentiation of this island species. Our findings show that drift as a consequence of Arctic climate cycling can rapidly reshape insular biodiversity. Arctic island species that lack genomic diversity and have evolved in response to past climate may have limited ability to respond to modern environmental changes.
Hyoscine butylbromide mode of action on bowel motility: From pharmacology to clinical practice
Authors: Corsetti Maura , Forestier Sylvie , Jiménez Marcel
Published: August 2022

Background

Hyoscine butylbromide (HBB) has been available for use as an antispasmodic since 1951 and is indicated for the treatment of abdominal pain associated with cramps. A previous review in 2007 summarized the evidence on the mode of action of HBB in vitro and in vivo in both animal and human studies. However, since then, novel publications have appeared within the literature and also our knowledge of what represents normal motility in humans has evolved.

Purpose

This review is the result of the collaboration between a basic scientist and clinicians with the aim of providing an updated overview of the mechanisms of action of HBB and its clinical efficacy to guide not only use in clinical practice, but also future research.
Policy dismantling and democratic regression in Brazil under Bolsonaro: Coalition politics, ideas, and underlying discourses
Authors: Milhorance Carolina
Published: August 2022

Drawing on a cost–benefit approach, policy dismantling literature typically examines case studies following omitted and blame‐avoidance strategies, which contrasts with the highly visible dismantling fostered by Bolsonaro's far‐right administration in Brazil. This study examines the mechanisms leading to this active process and places it in the context of major policy changes in several fields (i.e., rural development, land titling, social protection, environment, and protection of indigenous peoples). It shows that dismantling decisions were made incrementally by conservative coalitions that seized upon the economic crisis to consolidate a neoliberal turn; however, this turn was radicalized with the expansion of the conservative alliance and tied together by populist rhetoric. This study sheds light on the politics of policy dismantling and addresses it as a process of democratic backsliding.
Korea's trade policy and performance in turbulent times
Authors: Kang Moonsung , Park Innwon
Published: August 2022

This paper is a complementary study to gain a better understanding of Korea's recent trade performance in the context of the World Trade Organisation's (WTO) 2021 Trade Policy Review (TPR) on Korea. The TPR noted that Korea's external economic activities performed relatively well because Korea was able to limit the negative impact of recent turbulence in the global trade environment through enhanced regional cooperation and integration and reform since the East Asian financial crisis of the late 1990s. In addition, Korea's advanced information and communication technology has helped to mitigate external influences emanating from the global turmoil in the era of digitalisation. Evaluating Korea's recent trade performance, we found export's declining contribution to output growth and increasing vulnerability to external influences. Continuous efforts to widen and deepen regional cooperation together with efforts to rebalance value‐creation activities are required.
Effectiveness of trauma-informed, school-based interventions for children with a history of trauma or adverse experiences: an umbrella review protocol
Authors: McGraw Sarah , Palokas Michelle , Christian Robin
Published: August 2022

Objective:

The objective of this review is to synthesize evidence regarding the effectiveness of trauma-informed, school-based interventions for children with a history of trauma or adverse experiences as they pertain to academic performance and health outcomes, including behavior, mental health, and socio-emotional functioning.

Introduction:

Children and adolescents who face prolonged adverse experiences or trauma have a predisposition toward emotional, behavioral, mental, and physical health problems. Few children or adolescents who endure the repercussions of constant stress and hardships, or survivors of one or more types of trauma, receive the appropriate screening and diagnosis; therefore, they do not receive tailored care or interventions.

Inclusion criteria:

This review will include research syntheses pertaining to school-based, trauma-informed interventions for children and adolescents between the ages of 4 and 18 years with a history of adverse experiences or trauma. Comparisons will be made across all known school-based, trauma-informed interventions. This review will consider systematic reviews that include the following outcomes: mental health, behavior, academic performance, and/or socio-emotional functioning.

Methods:

The search strategy will aim to locate both published and unpublished systematic reviews. An initial limited search of MEDLINE (PubMed) and CINAHL (EBSCO) will identify articles on the topic. The search strategy will be adapted for each included information source. Articles published in English will be considered for inclusion and no date limits will apply. Two independent reviewers will critically appraise eligible studies. Extracted data will be tabulated and presented along with a narrative summary.
Capability as a concept in advanced practice nursing and education: a scoping review protocol
Authors: Whitfield Martha M. , Bleah Paulina , Bachynski Jovina Concepcion , Macdonald Danielle , Klein Tracy , Ross-White Amanda , Wilson Rosemary
Published: August 2022

Objective:

The objective of this scoping review is to identify and map how the concept of capability in advanced practice nursing and education is described in the literature.

Introduction:

Advanced practice nursing and education is often described in terms of the achievement of competencies. The concept of capability has been proposed as a more accurate description of the attributes of advanced practice nursing. Definitions of capability in advanced practice nursing vary, but often focus on the integration of prior knowledge, skills, resources, judgment, and experience when solving unanticipated problems or working in new situations.

Inclusion criteria:

This review will consider studies addressing the concept of individual capability in any setting related to advanced practice nursing education and practice. The working definition of capability in this review is a combination of knowledge, skills, experience, and competencies that enables advanced practice nurses to provide appropriate care for patients in both familiar and unfamiliar clinical settings. Advanced practice nurses will include nurses with both graduate education and an expanded scope of practice.

Methods:

Eight academic databases will be searched for qualitative, quantitative, and mixed methods study designs. The gray literature search will include policy and practice documents from nursing and health organization websites. Two reviewers will independently complete title and abstract screening prior to full-text review and data extraction. Articles published in English from 1975 to the present will be included. Other languages will be included if translations are available.