bluuebunny/crossref_metadata_2025 huggingface dataset:
Origin of wiring specificity in an olfactory map: dendrite targeting of projection neurons
Authors: Lam Wong Kenneth Kin , Li Tongchao , Fu Tian-Ming , Liu Gaoxiang , Lyu Cheng , Kohani Sayeh , Xie Qijing , Luginbuhl David J , Upadhyayula Srigokul , Betzig Eric , Luo Liqun
Published: December 2022

How does wiring specificity of neural maps emerge during development? Formation of the adultDrosophilaolfactory glomerular map begins with patterning of projection neuron (PN) dendrites at the early pupal stage. To better understand the origin of wiring specificity of this map, we created genetic tools to systematically characterize dendrite patterning across development at PN type–specific resolution. We find that PNs use lineage and birth order combinatorially to build the initial dendritic map. Specifically, birth order directs dendrite targeting in rotating and binary manners for PNs of the anterodorsal and lateral lineages, respectively. Two-photon– and adaptive optical lattice light-sheet microscope–based time-lapse imaging reveals that PN dendrites initiate active targeting with direction-dependent branch stabilization on the timescale of seconds. Moreover, PNs that are used in both the larval and adult olfactory circuits prune their larval-specific dendrites and re-extend new dendrites simultaneously to facilitate timely olfactory map organization. Our work highlights the power and necessity of type-specific neuronal access and time-lapse imaging in identifying wiring mechanisms that underlie complex patterns of functional neural maps.
TOR signalling regulates epithelial cell shape transition inDrosophilaoogenesis
Authors: Halder Sudipta , Ghosh Gaurab , Gayen Budhaditya , Prasad Mohit
Published: December 2022

Epithelial morphogenesis plays an important role in form generation, organ development, and maintenance of adult tissues in the metazoans. Given its wide implication, aberrant morphogenesis is linked to severe developmental defects and in a few instances also associated with tumorigenesis. Employing the model ofDrosophilaoogenesis, we have examined the role of the evolutionary conserved Target of Rapamycin (TOR) kinase pathway, a known regulator of cell growth and size in mediating shape transition of cuboidal cells to squamous epithelial fate. Utilizing genetic tools, immunohistochemistry, and live cell imaging, we demonstrate that TOR signaling is active and required for epithelial morphogenesis duringDrosophilaoogenesis. Further, loss of function analyses indicates that non-canonical TOR signaling functions through PAR-1 to mediate the removal of lateral cell adhesion molecule, Fasciclin 2, to allow proper squamous cell morphogenesis. In addition, we demonstrate the effect of TOR through PAR-1 on cell shape transition is mediated via the modulation of endocytosis. Overall, our data give novel insight into how TOR signaling mediates cell shape transition during epithelial morphogenesis in the metazoans.
LHX2 in germ cells control tubular organization in the developing mouse testis
Authors: Singh Neha , Singh Domdatt , Bhide Anshul , Sharma Richa , Bhowmick Shilpa , Patel Vainav , Modi Deepak
Published: December 2022

In the gonads of mammalian XY embryos, the organization of cords is the hallmark of testis development. This organization is thought to be controlled by interactions of the Sertoli cells, endothelial and interstitial cells with little or no role of germ cells. Challenging this notion, herein we show that the germ cells play an active role in the organization of the testicular tubules. We observed that the LIM-homeobox gene,Lhx2is expressed in the germ cells of the developing testis between E12.5-E15.5. InLhx2knockout-fetal testis there was altered expression of several genes not just in germ cells but also in the supporting (Sertoli) cells, endothelial cells, and interstitial cells. Further, loss ofLhx2led to disrupted endothelial cell migration and expansion of interstitial cells in the XY gonads. The cords in the developing testis ofLhx2knockout embryos are disorganized with a disrupted basement membrane. Together, our results show an important role ofLhx2in testicular development and imply the involvement of germ cells in the tubular organization of the differentiating testis.

Highlight

Lhx2is expressed in germ cells of developing mouse testis but is dispensable for germ cell and Sertoli cell specification

Loss ofLhx2disrupts testicular vascularization, leads to the expansion of interstitial cells, and alters the tubular organization

Germ cells govern the tubular organization in the developing testis

Graphical Abstract
SARS-CoV-2 accessory proteins ORF3a and ORF7a modulate autophagic flux and Ca2+homeostasis in yeast
Authors: Luis Garrido-Huarte José , Fita-Torró Josep , Viana Rosa , Pascual-Ahuir Amparo , Proft Markus
Published: December 2022

Virus infection involves the manipulation of key host cell functions by specialized virulence proteins. The SARS-CoV-2 small accessory proteins ORF3a and ORF7a have been implicated in favoring virus replication and spreading by inhibiting the autophagic flux within the host cell. Here, we apply yeast models to gain insights into the physiological functions of both SARS-CoV-2 small ORFs. ORF3a and ORF7a can be stably overexpressed in yeast cells, producing a decrease in cellular fitness. Both proteins show a distinguishable intracellular localization. ORF3a specifically localizes to the vacuolar membrane, whereas ORF7a targets the endoplasmic reticulum. Overexpression of ORF3a and ORF7a leads to the accumulation of Atg8 specific autophagosomes. However, the underlying mechanism is different for each viral protein as assessed by the quantification of the autophagic degradation of Atg8-GFP fusion proteins, which is inhibited by ORF3a and stimulated by ORF7a. Overexpression of both SARS-CoV-2 ORFs decreases cellular fitness upon starvation conditions, where autophagic processes become essential. These data are in agreement with a model where both small ORFs have synergistic functions in stimulating intracellular autophagosome accumulation, ORF3a by inhibiting autophagosome processing at the vacuole and ORF7a by promoting autophagosome formation at the ER. ORF3a has an additional function in Ca2+homeostasis. The overexpression of ORF3a confers calcineurin-dependent Ca2+tolerance and activates a Ca2+sensitive FKS2-luciferase reporter, suggesting a possible ORF3a-mediated Ca2+efflux from the vacuole. Taken together, we show that viral accessory proteins can be functionally investigated in yeast cells and that SARS-CoV-2 ORF3a and ORF7a proteins interfere with autophagosome formation and processing as well as with Ca2+homeostasis from distinct cellular targets.
A new strategic approach for R&D project portfolio selection using efficiency-uncertainty maps
Authors: Namazi Mehdi , Tavana Madjid , Mohammadi Emran , Bonyadi Naeini Ali
Published: December 2022

Purpose

New business practices and the globalization of markets force firms to take innovation as the fundamental pillar of their competitive strategy. Research and Development (R&D) plays a vital role in innovation. As technology advances and product life cycles become shorter, firms rely on R&D as a strategy to invigorate innovation. R&D project portfolio selection is a complex and challenging task. Despite the management's efforts to implement the best project portfolio selection practices, many projects continue to fail or miss their target. The problem is that selecting R&D projects requires a deep understanding of strategic vision and technical capabilities. However, many decision-makers lack technological insight or strategic vision. This article aims to provide a method to capitalize on the expertise of R&D professionals to assist managers in making informed and effective decisions. It also provides a framework for aligning the portfolio of R&D projects with the organizational vision and mission.

Design/methodology/approach

This article proposes a new strategic approach for R&D project portfolio selection using efficiency-uncertainty maps.

Findings

The proposed strategy plane helps decision-makers align R&D project portfolios with their strategies to combine a strategic view and numerical analysis in this research. The proposed strategy plane consists of four areas: Exploitation Zone, Challenge Zone, Desperation Zone and Discretion Zone. Mapping the project into this strategic plane would help decision-makers align their project portfolio according to the corporate perspectives.

Originality/value

The new approach combines the efficiency and uncertainty dimensions in portfolio selection into an integrated framework that: (i) provides a complete representation of the stochastic decision-making processes, (ii) models the endogenous uncertainty inherent in the project selection process and (iii) proposes a computationally practical and visually unique solution procedure for classifying desirable and undesirable R&D projects.
The interplay of contracts and trust: untangling between- and within-dyad effects
Authors: Wang Liwen , Jin Jason Lu , Yang Defeng
Published: December 2022

Purpose

Contracts and trust are two prominent governance mechanisms in buyer–supplier exchanges, yet controversy persists regarding the interplay between contracts and trust. This study aims to provide a new perspective to understand the debate by differentiating between- from within-dyad effects of contracts–trust relationships.

Design/methodology/approach

Based on survey data of 250 Chinese buyer–supplier relationships collected over two time periods, this study used two-level hierarchical linear modeling (HLM) with repeated measures to test the influence of contracts (trust) on trust (contracts) over time.

Findings

The authors find that for major buyer–supplier exchanges, contracts and trust tend to complement each other when comparing across dyads, but they likely substitute for each other in within-dyad settings.

Research limitations/implications

First, to illustrate the dynamic interactions between contracts and trust, this study collected data at two time periods and assumed continuous linear relationships of time with both contracts and trust. Further research should collect multiple waves of data to explore the complex, varying changes that arise over time. Second, this study’s findings are based on buyer–supplier relationships in China, whose unique cultural features may limit the generalizability of the results to other settings.

Practical implications

Channel managers can structure exchanges by devising detailed contracts that align incentives and demonstrate commitment, which helps build trust in a relationship. Channel managers should also pay special attention to the contingency effects of their transactional and relational features.

Originality/value

This study offers the first explicit test of the dynamic contracts–trust relationship, thereby establishing a more refined understanding of interplay between contracts and trust.
“Stealing from the language”: interest convergence and teachers’ advocacy for language-inclusive practices
Authors: Sedlacek Quentin Charles
Published: December 2022

Purpose

The purpose of this study is to support advocacy for racial and linguistic justice by examining teachers’ efforts to contest their colleagues' language-exclusive policies and practices.

Design/methodology/approach

The author used a critical and reconstructive discourse analysis guided by interest convergence theory to analyze narratives shared by teachers working to contest language-exclusive practices.

Findings

Teachers identified or created interest convergence to successfully contest specific practices. However, their arguments had the potential to be coopted for hegemonic purposes.

Originality/value

Previous studies have used interest convergence to analyze bilingual education policy. This study is one of the few to apply the theory to analyze other efforts to contest language-exclusive practices.
Digital information channels during the COVID-19 global health emergency through a situational awareness lens: a study of Pakistani citizens
Authors: Khalid Ayesha , Warraich Nosheen Fatima , Ali Irfan
Published: December 2022

Purpose

The main aim of this study was to know the role of digital information and communication channels in developing citizens’ understanding regarding COVID-19 with reference to situation awareness. Furthermore, the impact of gender, age, qualification and area of respondents on citizens' perception and comprehension of COVID-19 was also investigated.

Design/methodology/approach

This quantitative study used an online survey and received 377 usable responses. The instrument was developed with the help of literature, and it was based on two constructs (perception of the element and comprehension of the current situation) of the situational awareness (SA) model. Data were collected from Pakistani citizens through a convenient sampling technique.

Findings

It was observed that the majority of citizens used electronic media, Facebook and WhatsApp for accessing COVID-19-related information. World Health Organization website played an important role in developing citizens’ understanding. Alert messages through mobile phone and apps played role in developing citizen’s understanding regarding COVID-19 situation. They perceived that media was effective in providing social distancing techniques. Moreover, they believed that government campaigns were helpful. Findings revealed that there was no significant impact of gender, age, qualification and area on citizens' perceptions and comprehension of COVID-19 through media.

Originality/value

This study is helpful for authorities in decision-making regarding COVID-19 and also filled the literature gap as, to the best of the authors’ knowledge, no comprehensive study has been conducted regarding the SA of COVID-19.
Media, interpersonal communication, personal characteristics and online participation for climate change: structural equation modelling to determine digital discourse in Pakistan
Authors: Hussain Mudassar , Saleem Noshina , Hanan Mian Ahmad , Lodhi Rab Nawaz
Published: December 2022

Purpose

The purpose of this study is to fill the gap by researching the direct effects of media and personal characteristics on online participation in climate change, indirect effects when mediated by interpersonal communication and personal characteristics as predictors of media communications as sources of information about climate change.

Design/methodology/approach

A structured questionnaire is distributed to collect data about the uses of communication sources and online responses toward climate change by using a quota sampling technique. The structural equation modeling by using Smart PLS 4 is used to explore the effects’ size.

Findings

Small levels of direct and indirect effects are found. Direct effects are found in online newspapers, YouTube, television news, personal relevance toward climate change and political interest in online participation in climate change. Indirect effects are found of WhatsApp on online climate participation through interpersonal communication. Personal relevance toward climate change has motivated respondents to take information about climate change from Facebook. Climate skepticism is found among respondents who have received information from television news/talk shows, printed newspapers and WhatsApp.

Practical implications

University teachers in Pakistan will have to work on educational strategies to increase the knowledge of university students about energy generation through carbon and renewable energy sources.

Originality/value

The results of this study highlight the communicative-cultural dimensions of online discourse about climate change in the context of the less-researched country of Pakistan. This is the first study of researchers’ knowledge that comprehensively defines the digital media ecology in the context of climate change considering Pakistan.
Panel smooth transition regression approach to analyzing tourism development – housing price nexus in G7 countries
Authors: Yang Li , Khaskheli Asadullah , Raza Syed Ali , Shah Nida
Published: December 2022

Purpose

The purpose of this study is twofold: first is to examine the nonlinear relationship between tourism development and housing prices, and secondly, the role of economic growth in facilitating the materialization of tourism development and housing prices nexus in G7 countries.

Design/methodology/approach

The authors used the newly introduced econometric technique panel smooth transition regression (PSTR) model with two regimes on annual panel data from 1995 to 2018.

Findings

Results confirmed that the nexus between the tourism development and housing prices is nonlinear and regime dependent. Moreover, the results showed that the threshold level of economic growth above which tourism development increases the housing prices is 2.63%. The relationship above the threshold value is positive and growth enhancing, while below the threshold, tourism development has a negative effect on housing prices. The economic growth and housing prices also showed the U-shape relationship implying that at a certain level increase in economic growth decreases the housing prices but after a certain level increase in economic growth increases the housing prices.

Originality/value

This paper makes a unique contribution to the literature with reference to developed economies, being a pioneering attempt to investigate the nonlinear relationship between tourism development and housing prices and applying more rigorous and advanced econometric techniques like PSTR.
Revisiting the bullwhip effect: how can AI smoothen the bullwhip phenomenon?
Authors: Weisz Eric , Herold David M. , Kummer Sebastian
Published: December 2022

Purpose

Although scholars argue that artificial intelligence (AI) represents a tool to potentially smoothen the bullwhip effect in the supply chain, only little research has examined this phenomenon. In this article, the authors conceptualize a framework that allows for a more structured management approach to examine the bullwhip effect using AI. In addition, the authors conduct a systematic literature review of this current status of how management can use AI to reduce the bullwhip effect and locate opportunities for future research.

Design/methodology/approach

Guided by the systematic literature review approach from Durach et al. (2017), the authors review and analyze key attributes and characteristics of both AI and the bullwhip effect from a management perspective.

Findings

The authors' findings reveal that literature examining how management can use AI to smoothen the bullwhip effect is a rather under-researched area that provides an abundance of research avenues. Based on identified AI capabilities, the authors propose three key management pillars that form the basis of the authors' Bullwhip-Smoothing-Framework (BSF): (1) digital skills, (2) leadership and (3) collaboration. The authors also critically assess current research efforts and offer suggestions for future research.

Originality/value

By providing a structured management approach to examine the link between AI and the bullwhip phenomena, this study offers scholars and managers a foundation for the advancement of theorizing how to smoothen the bullwhip effect along the supply chain.
Empirical analysis of Lean Six Sigma implementation barriers in healthcare sector using fuzzy DEMATEL approach: an Indian perspective
Authors: Singh Mahipal , Rathi Rajeev , Jaiswal Ajay , Manishbhai Shah Dhyey , Gupta Shaptarshi Sen , Dewangan Abhishek
Published: December 2022

Purpose

The present study aims to explore the barriers to Lean Six Sigma (LSS) implementation in the healthcare sector and develop the ranking of finalized barriers using the Decision-Making Trial and Evaluation Laboratory (DEMATEL) approach under a fuzzy environment.

Design/methodology/approach

The LSS barriers are identified through the literature review and validated by the expert's opinion and statistical analysis. A total of 124 experts were identified through the purposive sampling method for conducting this study. A questionnaire survey method is used to collect the data related to identified LSS barriers in the healthcare sector. The screened barriers are ranked through the Fuzzy DEMATEL approach.

Findings

In this study, a total of 21 barriers were identified with the help of a systematic literature review and screened 13 significant barriers by the expert opinions of healthcare personnel. The result reveals that “Lack of top management commitment and support, lack of awareness about LSS”, “resistance to culture change and inadequate resources emerges as the most critical barriers”. The prioritization of barriers facilitates the managers to make effective policies and guidelines for LSS implementation in healthcare organizations.

Practical implications

To avoid LSS implementation failure, the practitioners and researchers need to focus on LSS barriers as per suggested ranking more conventionally and make plans and adoption policies accordingly.

Originality/value

This study is unique in terms of investigation and empirical analysis of LSS implementation barriers in the healthcare sector in the Indian context. The outcomes of the present study will help the managers of healthcare organizations to make the strategies and policies for LSS implementation as per the recommended LSS barriers.
Safety and efficacy of high‐dose clobetasol propionate 0.05% in cutaneous lichen planus
Authors: Melin Audrey , Bouchereau Sarah , Guelimi Robin , Bergqvist Christina , Condamina Morgane , Giraud‐Kerleroux Laura , Hirsch Gaëlle , Hua Camille , Wolkenstein Pierre , Skayem Charbel , Le Cleach Laurence
Published: December 2022

Cutaneous lichen planus is a highly pruritic dermatosis with an unmet need in its management. The aim of this study was to evaluate the short‐term effect and tolerance of high doses of clobetasol propionate 0.05% in cutaneous lichen planus. We conducted a single‐center retrospective cohort study from 2017 to 2021. All adults treated with high‐dose (>5 g/day) clobetasol propionate 0.05% for cutaneous lichen planus were included. Patients with less than 10% affected body surface area at initial presentation or who received concomitant systemic therapy were excluded. The primary endpoint was the rate of complete remission by week 16. Secondary endpoints included maximum daily and median cumulative doses, reduction in pruritus and occurrence of adverse events. Fifty‐seven patients, 60% female, with a mean age of 48 years (min–max,18–83) were included. Cutaneous lichen planus had been present for a median duration of 2 months at initial presentation (min–max, 1–4) and involved a median body surface area of 27%. Pruritus was reported by 55/57 (96%) patients. At week 16, 41/57 (72%) patients had achieved complete remission without treatment modification, among whom 25/41 (61%) had achieved it at week 6. The median daily and cumulative doses were, respectively, 20 g/day (IQR, 10–20) and 560 g (IQR, 320–925). Three patients experienced mild adverse events. No statistical association was demonstrated between the duration of the disease before treatment initiation and clinical response. In conclusion, high‐dose clobetasol propionate 0.05% seems to be an effective, well‐tolerated, and easy‐to‐implement treatment for cutaneous lichen planus.
TAPO in first‐line osimertinib therapy and continuation of osimertinib
Authors: Mimura Chihiro , Kaneshiro Kazumi , Fujimoto Shodai , Dokuni Ryota , Iwamoto Natsuhiko , Matsumura Kanoko , Hatakeyama Yukihisa , Kono Yuko , Tachihara Motoko
Published: December 2022

Background

Osimertinib is associated with a relatively high frequency of drug‐induced interstitial lung disease (D‐ILD), and transient asymptomatic pulmonary opacities (TAPO) have been reported to occur during osimertinib administration. The frequency of TAPO during first‐line treatment and the pros and cons of osimertinib continuation is unknown.

Methods

This was a multicenter, retrospective study. The purpose of this study was to research the frequency of TAPO and to evaluate osimertinib continuation in first‐line therapy. We also evaluated progression‐free survival (PFS) including subgroup analysis.

Results

From August 2018 to December 2020, 133 patients were enrolled into the study. The median observation period was 23.2 months (0.3–48.3 months). Thirty patients (22.6%) experienced D‐ILD events, including 16 patients (12.1%) with CTCAE grade 1, five patients (3.8%) with grade 2, and nine patients (6.7%) with grade 3 and above D‐ILD. Among the patients with grade 1 D‐ILD, 11 cases (8.3%) of TAPO were observed, and all patients succeeded in osimertinib continuation. The TAPO images were characterized by localized patchy opacities (73%). The median PFS was 22.6 months (95% confidence interval [CI]: 17.8–28.7 months). Patients with TAPO had a significantly longer PFS than patients with non‐TAPO D‐ILD in the multivariate analysis.

Conclusions

This study showed that grade 1 D‐ILD might include TAPO and that patients with TAPO might have good PFS. We need to consider the possibility of osimertinib continuation when lung opacities appear.
Controlling the controls: what is negative pressure wound therapy compared to in clinical trials?
Authors: McMillan Hayley , Vo Uyen G. , Moss Jana‐Lee , Barry Ian P. , Bosanquet David C. , Richards Toby
Published: December 2022

Aim

Surgical site infections (SSIs) are common following colorectal operations. Clinical trials suggest that closed incision negative pressure wound therapy (ciNPWT) may reduce SSIs compared to a ‘standard of care’ group. However, wound management in the standard of care group may vary. The aim of this review was to assess the control arms in trials of ciNPWT for potential confounding variables that could influence the rates of SSI and therefore the trial outcomes.

Methods

A mapping review of the PubMed database was undertaken in the English language for randomized controlled trials that assessed, in closed surgical wounds, the use of ciNPWT compared to standard of care with SSI as an outcome. Data regarding wound care to assess potential confounding factors that may influence SSI rates were compared between the ciNPWT and standard of care groups. Included were the method of wound closure, control dressing type, frequency of dressing changes and postoperative wound care (washing).

Results

Twenty‐seven trials were included in the mapping review. There was heterogeneity in ciNPWT duration. There was little control in the comparator standard of care groups with a variety of wound closure techniques and different control dressings used. Overall standard of care dressings were changed more frequently than the ciNPWT dressing and there was no control over wound care or washing. No standard for ‘standard of care’ was apparent.

Conclusion

In randomized trials assessing the intervention of ciNPWT compared to standard of care there was considerable heterogeneity in the comparator groups and no standard of care was apparent. Heterogeneity in dressing protocols for standard of care groups could introduce potential confounders impacting SSI rates. There is a need to standardize care in ciNPWT trials to assess potential meaningful differences in SSI prevention.
Beyond Zoom Fatigue: Ritual and Resilience in Remote Meetings
Authors: THOMAS SUZANNE , SHERRY JOHN , CHIERICHETTI REBECCA , ASLAN SINEM , MANDACHE LUMINIŢA‐ANDA
Published: December 2022

COVID‐19 has precipitated a massive social experiment – the sudden shift of millions of knowledge workers from their traditional offices to homes or other remote work locations. This has inspired heated debates and new ways of imagining the future of work. This paper hopes to contribute to a better understanding of these changes by reporting on the results of several dozen in‐depth interviews with remote workers from a variety of geographies, industries and professions. We focus in particular on their experiences of remote meetings, with special attention to complaints workers have with their current implementation. As we learned, workers' complaints tended to be driven by social – rather than productivity or technical – concerns. We explore this social dimension in depth, propose a framework for thinking about meetings as rituals, and suggest how this emphasis might inform the design of technology to support remote collaboration.
LQM10, a guanylhydrazone derivative, reduces nociceptive and inflammatory responses in mice
Authors: Noé João Paulo , de Souza‐Ferro Jamylle Nunes , da Silva‐Rodrigues Érica Erlanny , da Silva‐Júnior Edeildo Ferreira , Alexandre‐Moreira Magna Suzana , de Araújo‐Junior João Xavier , Barreto Emiliano
Published: December 2022

In the present study, we examined the antinociceptive and anti‐inflammatory activities of a guanylhydrazone derivative, (E)‐(3,5‐di‐tert‐butyl‐4‐hydroxybenzylidene)‐2‐guanylhydrazone hydrochloride (LQM10), in mice. The antinociceptive effect was determined by assessing behavioural responses in different pain models, while anti‐inflammatory activity was examined in carrageenan‐induced pleurisy. Intraperitoneal LQM10 administration reduced the acetic acid‐induced nociceptive behaviour, a phenomenon that was unaltered by pretreatment with yohimbine, atropine, naloxone or glibenclamide. In the formalin assay, LQM10 reduced nociceptive behaviour only in the second phase, indicating an inhibitory effect on inflammatory pain. LQM10 did not alter the pain latency in the hot plate assay and did not impact the locomotor activity of mice in the rotarod assay. In the carrageenan‐induced pleurisy assay, LQM10 treatment inhibited critical events involved in inflammatory responses, namely, leucocyte recruitment, plasma leakage and increased inflammatory mediators (tumour necrosis factor Like Properties of Chalchones and Flavonoid Derivatives [TNF]‐α and interleukin [IL]‐1β) in the pleural exudate. Overall, these results indicate that LQM10 exhibits antinociceptive effects associated with peripheral mechanisms and anti‐inflammatory activity mediated via a reduction in leucocyte migration and proinflammatory mediators, rendering this compound a promising candidate for treating pain and inflammatory process.
Distribution and geographic differences in stable isotope ratios of diamond squid Thysanoteuthis rhombus (Cephalopoda: Thysanoteuthidae) in Japanese waters
Authors: Ohshimo Seiji , Kodama Taketoshi , Tawa Atsushi , Tanaka Hiroshige , Tanaka Yosuke , Yasuhara Go , Tokuyasu Michihiro , Minami Yoichi
Published: December 2022

Diamond squid Thysanoteuthis rhombus (Troschel, 1857), which can grow to a dorsal mantle length of ~100 cm in 1 year, is an important fisheries resource in subtropical and temperate waters worldwide. Around Japan, it is an important resource in the East China Sea, Sea of Japan, and western North Pacific Subtropical Gyre, including the Kuroshio area. It is not known if linkages occur between these habitats. To clarify the species distribution, we estimated the habitat of young squid using a generalized additive model based on trawl surveys and analyzed carbon and nitrogen stable isotope ratios (δ13C and δ15N) in tissue samples. Based on trawl observations, young squid were distributed around northeastern Taiwan and the Okinawa Islands in June–July and in the Sea of Japan and the Kuroshio extension areas in August–September. We observed ontogenetic changes in the stable isotope ratios. The δ15N values in large diamond squid (dorsal mantle length > 400 mm) were significantly lower in the Pacific than those in other areas. Considering that the δ15N of forage fish is low in the Pacific and high in the East China Sea and Sea of Japan, large diamond squid in the northwest Pacific presumably have two distinct habitats.
The association between nurse managers’ transformational leadership and quality of patient care: A systematic review
Authors: Alanazi Naif H. , Alshamlani Yousef , Baker Omar Ghazi
Published: December 2022

Aim

To examine and summarize the reported association of nurse managers’ transformational leadership and quality of patient care based on the perceptions of registered nurses.

Background

Transformational leadership behaviors of nurse managers result in staff nurses’ satisfaction and retention and patient satisfaction. Patient safety and quality of care are vital to high‐performing healthcare organizations. Perceptions of registered nurses are important because nurses are frontline healthcare providers fundamental to patient safety and quality of care and are considered the final line of defense in preventing adverse events and errors and improving the safety of patients.

Materials and methods

We  searched the CINAHL, ProQuest, PubMed, Science Direct, and Web of Science databases for evidence published between 2018 and 2022 in the English language. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines in carrying out this meta‐analysis.

Results

Nine quantitative studies were appraised using the Joanna Briggs Institute checklists and were included in the final review that involved a total sample of 3633 registered nurses. The included studies were reported across Asian, Middle East, and European countries within the past five years. The association between the transformational leadership behaviors of nurse managers and the quality of patient care was found in varying degrees (i.e., insignificant, weak, indirect, and strong direct association) based on the perceptions of registered nurses.

Conclusions

There is a direct and indirect association between the transformational leadership behaviors of nurse managers and the quality of patient care internationally. This association is influenced by confounding and mediating factors, including gender, organizational culture, structural empowerment, and job satisfaction.

Implications for nursing and health policies

Healthcare organizations need to support nursing leaders to have a stronger transformational leadership style by considering several factors that influence their leadership to improve the quality of patient care their staff nurses provide at the bedside.
New atrial arrhythmia occurrence in single chamber implantable cardioverter defibrillator patients: A real‐world investigation
Authors: Patel Divyang , Rao Archana , Friedman Paul A. , Deshmukh Abhishek J. , Lande Jeff , Murphy Jeffrey A. , Brown Mark L. , Lexcen Daniel R. , Wilkoff Bruce L.
Published: December 2022

Introduction

A current limitation of single chamber implantable cardioverter defibrillators (ICDs) is the lack of an atrial lead to reliably detect atrial fibrillation (AF) episodes. A novel ventricular based atrial fibrillation (VBAF) detection algorithm was created for single chamber ICDs to assess R‐R variability for detection of AF.

Methods

Patients implanted with Visia AF™ ICDs were prospectively enrolled in the Medtronic Product Surveillance Registry from December 15, 2015 to January 23, 2019 and followed with at least 30 days of monitoring with the algorithm. Time to device‐detected daily burden of AF ≥ 6 min, ≥6 h, and ≥23 h were reported. Clinical actions after device‐detected AF were recorded.

Results

A total of 291 patients were enrolled with a mean follow‐up of 22.5 ± 7.9 months. Of these, 212 (73%) had no prior history of AF at device implant. However, 38% of these individuals had AF detected with the VBAF algorithm with daily burden of ≥6 min within two years of implant. In these 80 patients with newly detected AF by their ICD, 23 (29%) had a confirmed clinical diagnosis of AF by their provider. Of patients with a clinical diagnosis of AF, nine (39%) were newly placed on anticoagulation, including five of five (100%) patients having a burden >23 h.

Conclusions

Continuous AF monitoring with the new VBAF algorithm permits early identification and actionable treatment for patients with undiagnosed AF that may improve patient outcomes.
Apolipoprotein E4 inhibits γ‐secretase activity via binding to the γ‐secretase complex
Authors: Sun Yang , Islam Sadequl , Gao Yuan , Nakamura Tomohisa , Zou Kun , Michikawa Makoto
Published: December 2022

The mechanisms of amyloid accumulation in familial Alzheimer's disease (FAD) and sporadic AD (SAD) are controversial. In FAD, mutations in presenilin (PSEN) impair γ‐secretase activity and lead to abnormal amyloid β–protein (Aβ) production, thereby increasing the Aβ42/40 ratio. SAD is postulated to be caused by decreased Aβ clearance of apolipoprotein E4 (APOE4), the strongest risk factor for SAD. However, whether intracellular APOE4 affects Aβ production is unclear. Using APOE3 and APOE4 knock‐in (KI) mouse brain and primary cultured fibroblasts from these mice, in this study, we demonstrated that APOE3 and APOE4 bind to the γ‐secretase complex and isoform‐dependently regulate its activity and Aβ production. We found that Aβ40 levels and γ‐secretase activity were higher in APOE knockout mouse brain than in wild‐type mouse brain. APOE4‐KI fibroblasts had significant lower Aβ levels and γ‐secretase activity but higher Aβ42/40 ratio compared with APOE3‐KI cells, indicating that APOE4‐KI reduces Aβ production by inhibiting γ‐secretase activity. Interestingly, the levels of γ‐secretase complex bound to APOE4 are higher than those bound to APOE3, and the levels of γ‐secretase complex in the brain and fibroblasts of APOE4‐KI mice were higher than those of APOE3‐KI mice. Taken together, our findings demonstrate that intracellular APOE4 inhibits Aβ production, more preferentially inhibits Aβ40 production, and thereby induces an increase in the Aβ42/40 ratio via binding to the γ‐secretase complex. These results suggest a novel mechanism in which intracellular APOE4 contributes to the pathogenesis of SAD by inhibiting γ‐secretase activity.

image
Exploring the linkage between family financial struggle and children's bullying victimization: Implications for nursing and psychotherapeutic practices
Authors: Hong Jun Sung , Choi Jungtae , O'Donnell Lisa A. , Espelage Dorothy L. , Albdour Maha , Wu Chi‐Fang
Published: December 2022

Purpose

A few studies have found that children whose families are economically disadvantaged and financially struggling are at an elevated risk of victimization by their peers. However, extant research is largely descriptive. To address this gap, this study empirically tested the proposed pathways from family financial struggle to children's bullying victimization, including the role of barriers to healthcare access in this association using a nationally representative sample.

Design and Methods

The study utilizes the 2016 National Survey of Children's Health, a survey of a cross‐sectional, weighted probability sample of US children (ages 0–17 years) living in 50 states and the District of Columbia, and their caregivers. The sample used for the current study included 14,374 racially and ethnically diverse caregivers of children, aged 6–11 years.

Results

Positive significant associations between family financial struggle and children's bullying victimization, and between financial struggle and barriers to healthcare access were found. Barriers to healthcare access mediated the association between family financial struggle and bullying victimization.

Practice Implications

Given the documented effects of bullying victimization on children, findings point to the importance of developing psychotherapeutic practices that are appropriate for children who are flagged as “high‐risk.”
Do brachycephaly and nose size predict the severity of obstructive sleep apnea (OSA)? A sample‐based geometric morphometric analysis of craniofacial variation in relation to OSA syndrome and the role of confounding factors
Authors: Daboul Amro , Krüger Markus , Ivanovska Tatyana , Obst Anne , Ewert Ralf , Stubbe Beate , Fietze Ingo , Penzel Thomas , Hosten Norbert , Biffar Reiner , Cardini Andrea
Published: December 2022

Obstructive sleep apnea is a common disorder that leads to sleep fragmentation and is potentially bidirectionally related to a variety of comorbidities, including an increased risk of heart failure and stroke. It is often considered a consequence of anatomical abnormalities, especially in the head and neck, but its pathophysiology is likely to be multifactorial in origin. With geometric morphometrics, and a large sample of adults from the Study for Health in Pomerania, we explore the association of craniofacial morphology to the apnea–hypopnea index used as an estimate of obstructive sleep apnea severity. We show that craniofacial size and asymmetry, an aspect of morphological variation seldom analysed in obstructive sleep apnea research, are both uncorrelated to apnea–hypopnea index. In contrast, as in previous analyses, we find evidence that brachycephaly and larger nasal proportions might be associated to obstructive sleep apnea severity. However, this correlational signal is weak and completely disappears when age‐related shape variation is statistically controlled for. Our findings suggest that previous work might need to be re‐evaluated, and urge researchers to take into account the role of confounders to avoid potentially spurious findings in association studies.
Progression patterns and therapeutic sequencing following immune checkpoint inhibition for hepatocellular carcinoma: An international observational study
Authors: Talbot Thomas , D'Alessio Antonio , Pinter Matthias , Balcar Lorenz , Scheiner Bernhard , Marron Thomas U. , Jun Tomi , Dharmapuri Sirish , Ang Celina , Saeed Anwaar , Hildebrand Hannah , Muzaffar Mahvish , Fulgenzi Claudia A. M. , Amara Suneetha , Naqash Abdul Rafeh , Gampa Anuhya , Pillai Anjana , Wang Yinghong , Khan Uqba , Lee Pei‐Chang , Huang Yi‐Hsiang , Bengsch Bertram , Bettinger Dominik , Mohamed Yehia I. , Kaseb Ahmed , Pressiani Tiziana , Personeni Nicola , Rimassa Lorenza , Nishida Naoshi , Kudo Masatoshi , Weinmann Arndt , Galle Peter R. , Muhammed Ambreen , Cortellini Alessio , Vogel Arndt , Pinato David J.
Published: December 2022

Background and Aims

Different approaches are available after the progression of disease (PD) to immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC), including the continuation of ICI, treatment switching to tyrosine kinase inhibitors (TKIs) and cessation of anticancer therapy. We sought to characterise the relationship between radiological patterns of progression and survival post‐ICI, also appraising treatment strategies.

Methods

We screened 604 HCC patients treated with ICIs, including only those who experienced PD by data cut‐off. We evaluated post‐progression survival (PPS) according to the treatment strategy at PD and verified its relationship with radiological patterns of progression: intrahepatic growth (IHG), new intrahepatic lesion (NIH), extrahepatic growth (EHG), new extrahepatic lesion (NEH) and new vascular invasion (nVI).

Results

Of 604 patients, 364 (60.3%) experienced PD during observation. Median PPS was 5.3 months (95% CI: 4.4–6.9; 271 events). At the data cut‐off, 165 patients (45%) received no post‐progression anticancer therapy; 64 patients (17.6%) continued ICI beyond PD. IHG (HR 1.64 [95% CI: 1.21–2.22]; p = .0013) and nVI (HR 2.15 [95% CI: 1.38–3.35]; p = .0007) were associated with shorter PPS. Multivariate models adjusted for progression patterns, treatment line and albumin‐bilirubin grade and Eastern Cooperative Oncology Group performance status at PD confirmed receipt of ICI beyond PD with (HR 0.17, 95% CI: 0.09–0.32; p < .0001) or without subsequent TKI (HR 0.39, 95% CI: 0.26–0.58; p < .0001) as predictors of prolonged PPS versus no anticancer therapy.

Conclusions

ICI‐TKI sequencing is a consolidated option in advanced HCC. nVI and IHG predict a poorer prognosis. Despite lack of recommendation, the continuation of ICI beyond progression in HCC is adopted clinically: future efforts should appraise which patients benefit from this approach.
From whom Bells tolls: Reclassifying Bells among CR chondrites and implications for the formation conditions of CR parent bodies
Authors: Marrocchi Yves , Jacquet Emmanuel , Neukampf Julia , Villeneuve Johan , Zolensky Michael E.
Published: December 2022

The ungrouped carbonaceous chondrite (CC) Bells has long been considered petrographically similar to CM chondrites based on its matrix abundance and degree of aqueous alteration, but also shows significant isotopic affinities to CR chondrites. Its taxonomic status is thus important for clarifying the relationship of the CRHB (formerly “CR”) clan with other CCs. In this study, we measured the oxygen isotopic compositions of olivines in type I chondrules and isolated olivine grains in Bells. Bells olivines mostly have ∆17O > −4‰, similar to CR chondrites but unlike other CCs that are rich in refractory inclusions, in which chondrules are generally richer in 16O. Therefore, Bells is a CR chondrite (albeit an anomalous one), most similar to the rare, matrix‐rich CRs like Al Rais. These chondrites (i) may not necessarily derive from the same primary parent body as mainstream CRs, (ii) bear witness to significant variations of the matrix/chondrule ratio within the CRHB clan, and (iii) may be a good analog for samples retrieved by the space mission OSIRIS‐REx.
Lack of evidence that Pseudomonas aeruginosaAmpDh3‐PA0808 constitute a type VI secretion system effector–immunity pair
Authors: Colautti Jake , Bullen Nathan P. , Whitney John C.
Published: December 2022

Type VI secretion systems (T6SSs) are cell envelope‐spanning protein complexes that Gram‐negative bacteria use to inject a diverse arsenal of antibacterial toxins into competitor cells. Recently, Wang et al. reported that the H2‐T6SS of Pseudomonas aeruginosa delivers the peptidoglycan recycling amidase, AmpDh3, into the periplasm of recipient cells where it is proposed to act as a peptidoglycan degrading toxin. They further reported that PA0808, the open reading frame downstream of AmpDh3, encodes an immunity protein that localizes to the periplasm where it binds to and inactivates intercellularly delivered AmpDh3, thus protecting against its toxic activity. Given that AmpDh3 has an established role in cell wall homeostasis and that no precedent exists for cytosolic enzymes moonlighting as T6SS effectors, we attempted to replicate these findings. We found that cells lacking PA0808 are not susceptible to bacterial killing by AmpDh3 and that PA0808 and AmpDh3 do not physically interact in vitro or in vivo. Additionally, we found no evidence that AmpDh3 is exported from cells, including by strains with a constitutively active H2‐T6SS. Finally, subcellular fractionation experiments and a 1.97 Å crystal structure reveal that PA0808 does not contain a canonical signal peptide or localize to the correct cellular compartment to confer protection against a cell wall targeting toxin. Taken together, these results cast doubt on the assertion that AmpDh3‐PA0808 constitutes an H2‐T6SS effector–immunity pair.