bluuebunny/crossref_metadata_2025 huggingface dataset:
Food recognition in a blood-feeding insect: characterization of the pharyngeal taste organ
Authors: Ortega-Insaurralde Isabel , Latorre-Estivalis José Manuel , Costa-da-Silva Andre Luis , Cano Agustina , Insausti Teresita C. , Morales Hector Salas , Pontes Gina , de Astrada Martín Berón , Ons Sheila , DeGennaro Matthew , Barrozo Romina B.
Published: November 2022

Background

Obligate blood-feeding insects obtain the nutrients and water necessary to ensure survival from the vertebrate blood. The internal taste sensilla, situated in the pharynx, evaluate the suitability of the ingested food. Here, through multiple approaches, we characterized the pharyngeal organ (PO) of the hematophagous kissing bugRhodnius prolixusto determine its role in food assessment. The PO, located antero-dorsally in the pharynx, comprises 8 taste sensilla that become bathed with the incoming blood.

Results

We showed that these taste sensilla house gustatory receptor neurons projecting their axons through the labral nerves to reach the subesophageal zone in the brain. We found that these neurons are electrically activated by relevant appetitive and aversive gustatory stimuli such as NaCl, ATP and caffeine. Using RNA-Seq, we examined the expression of sensory-related gene families in the PO. We identified gustatory receptors, ionotropic receptors, transient receptor potential channels, pickpocket channels, opsins, takeouts, neuropeptide precursors, neuropeptide receptors and biogenic amine receptors. RNA interference assays demonstrated that the pickpocket channelRproppk014276is necessary for salt detection during feeding.

Conclusion

We provide evidence of the role of the pharyngeal organ in food evaluation. This work shows the first comprehensive characterization of a pharyngeal taste organ in a hematophagous insect.
Single-cell RNA-sequencing implicates venous endothelial cells as a source of VEGF-A-mediated neo-angiogenesis in neuroinflammation
Authors: Shahriar S. , Biswas S. , Zhao K. , Akcan U. , Tuohy M. C. , Glendinning M. D. , Kurt A. , Wayne C. R. , Prochilo G. , Price M. Z. , Brekken R. A. , Menon V. , Agalliu D.
Published: November 2022

Histopathological studies of multiple sclerosis (MS), a demyelinating disease of the central nervous system (CNS), and its animal model, experimental autoimmune encephalomyelitis (EAE), have found newly formed leaky vessels in demyelinated acute and chronic plaques, in addition to blood-brain barrier (BBB) damage in existing vessels, that exacerbate disease pathology by increasing infiltration of immune cells. Which vessel subtypes and signaling pathways generate these aberrant vessels is poorly understood. Using single-cell RNA-sequencing andin vivovalidation, we find that transcriptome signatures of neo-angiogenesis arise in venous endothelial cells in both acute and chronic EAE, and correlate with upregulation in VEGF-A signaling. These neo-angiogenic markers are also increased in acute and chronic MS lesions. Treatment with a VEGF-A blocking antibody diminishes neo-angiogenic transcriptomic signatures and vascular proliferationin vivo, but does not restore BBB function or ameliorate significantly EAE pathology. Therefore, anti-angiogenic therapies in combination with immunomodulatory therapies may benefit MS progression.
Cell-type specific developmental defects inPTEN-mutant cortical organoids converge on abnormal circuit activity
Authors: Pigoni Martina , Uzquiano Ana , Paulsen Bruna , Kedaigle Amanda , Yang Sung Min , Symvoulidis Panagiotis , Adiconis Xian , Velasco Silvia , Sartore Rafaela , Kim Kwanho , Tucewicz Ashley , Tsafou Kalliopi , Jin Xin , Barrett Lindy , Chen Fei , Boyden Ed , Regev Aviv , Levin Joshua Z. , Arlotta Paola
Published: November 2022

De novoheterozygous loss-of-function mutations inPTENare strongly associated with Autism spectrum disorders (ASD); however, it is unclear how heterozygous mutations in this gene affects different cell types during human brain development, and how these effects vary across individuals. Here, we used human cortical organoids from different donors to identify cell-type-specific developmental events that are affected by heterozygous mutations inPTEN. We profiled individual organoids by single-cell RNA-seq, proteomics and spatial transcriptomics, and revealed abnormalities in developmental timing in human outer radial glia progenitors and deep layer cortical projection neurons, which varied with the donor genetic background. Calcium imaging in intact organoids showed that both accelerated and delayed neuronal development phenotypes resulted in similar abnormal activity of local circuits, irrespective of genetic background. The work reveals donor-dependent, cell-type specific developmental phenotypes ofPTENheterozygosity that later converge on disrupted neuronal activity.
Brain region-specific changes in neurons and glia and dysregulation of dopamine signaling inGrin2amutant mice
Authors: Farsi Zohreh , Nicolella Ally , Simmons Sean K , Aryal Sameer , Shepard Nate , Brenner Kira , Lin Sherry , Herzog Linnea , Shin Wangyong , Gazestani Vahid , Song Bryan , Bonanno Kevin , Keshishian Hasmik , Carr Steven A , Macosko Evan , Datta Sandeep Robert , Dejanovic Borislav , Kim Eunjoon , Levin Joshua Z , Sheng Morgan
Published: November 2022

Schizophrenia disease mechanisms remain poorly understood, in large part due to a lack of valid animal models. Rare heterozygous loss-of-function mutations inGRIN2A, encoding a subunit of the NMDA (N-methyl-d-aspartate) receptor, greatly increase the risk of schizophrenia. By transcriptomic, proteomic, electroencephalogram (EEG) recording and behavioral analysis, we report that heterozygousGrin2amutant mice show: (i) large-scale gene expression changes across multiple brain regions and in neuronal (excitatory and inhibitory) and non-neuronal cells (astrocytes, oligodendrocytes); (ii) evidence of reduced activity in prefrontal cortex and increased activity in hippocampus and striatum; (iii) elevated dopamine signaling in striatum; (iv) altered cholesterol biosynthesis in astrocytes; (v) reduction of glutamatergic receptor signalin g proteins in the synapse; (iv) heightened gamma oscillation power in EEG; (vi) aberrant locomotor behavioral pattern opposite of that induced by antipsychotic drugs. These findings reveal potential pathophysiologic mechanisms, provide support for both the “hypo-glutamate” and “hyper-dopamine” hypotheses of schizophrenia, and underscore the utility ofGrin2a-deficient mice as a new genetic model of schizophrenia.
A review of reviews exploring patient and public involvement in population health research
Authors: Vinnicombe Soo , Noyes Jane
Published: November 2022

Introduction

Patient and public involvement (PPI) is increasingly seen as something that is integral to research and of importance to research funders. There is general recognition that PPI is the right thing to do for both moral and practical reasons. The aim of this review of reviews is to examine how PPI can be done ‘properly’ by looking at the evidence that exists from published reviews and assessing it against the UK Standards for Public Involvement in Research, as well as examining the specific features of population health research that can make PPI more challenging.

Methods

A review of reviews was carried out following the 5-stage Framework Synthesis method.

Results

In total 31 reviews were included. There is a lack of current research or clarity around Governance and Impact when findings are mapped against UK Standards for Public Involvement in Research. It was also clear that there is little knowledge around PPI with under-represented groups. There are gaps in knowledge about how to ensure key specific attributes of population health research are addressed for PPI team members – particularly around how to deal with complexity and the data-driven nature of the research. Two tools were produced for researchers and PPI members to further improve their PPI activity within population health research and health research more generally: A framework of recommended actions to address PPI in population health research, and guidance on integrating PPI based on the UK Standards for Public Involvement in Research.

Conclusions

Facilitating PPI in population health research is challenging due to the nature of this type of research and there is far less evidence on how to do PPI well in this context. The tools can help researchers identify key aspects of PPI that can be integrated when designing PPI within projects. Findings also highlight specific areas where more research or discussion is needed.
iSupport-J, the Japanese version of an internet-based self-learning and psychological assessment program for dementia caregivers: study protocol for a randomized, waiting-list controlled study
Authors: Yamashita Shingo , Yokoi Yuma , Matsui Makoto , Nozaki Kazumi , Fujimaki Chinatsu , Wada Ayumu , Iwata Naoya , Sugawara Norio , Omachi Yoshie
Published: November 2022

Background

The number of people with dementia in Japan will estimate to increase to roughly 20% of those aged 65 and over (approximately 7 million people) by 2025. Around the world, the number of people with dementia is increasing by 7.7 million per year, and caregivers’ depression, stress, social isolation, and sleep disorders due to the burden of caregiving are also increasing. Economic losses worldwide due to physical and mental health problems of dementia caregivers, reduced work hours due to caregiving, and job loss are estimated to be $252 billion in 2010. In addition, the risk of abuse against the caregiver increases as the caregiver is affected by physical and mental illness. Psychosocial interventions such as cognitive behavioral therapy have reportedly reduced caregivers’ mental distress and improved their health. Since caregivers have significant time and physical limitations due to caregiving, it is promising that interventions using the internet, which have few limitations in terms of location and time, will be helpful, along with its low cost.

Methods

This is a two-arm, randomized, waitlist-controlled trial. Participants will be randomized with a 1:1 ratio to either the immediate or late access group. The early intervention group will be able to use iSupport for three months, followed by allocation and follow-ups until six months. In the waitlist group, iSupport can be available for three months from the end of the Month 3 evaluation. Scheduled evaluation periods are Months 1, 3, and 6.

Discussion

We plan to begin recruiting for the trial in January 2021. We plan to finish the inclusion by June 2021 and complete all data collection by December 2021. Once all data collection is complete, we plan to analyze the data by April 2022; we aim to publish the results in a manuscript by the end of 2022.

Trial Registration

UMIN-CTR, UMIN000042957, registered on January 9, 2021.
β-Cyclodextrins as affordable antivirals to treat coronavirus infection
Authors: Raïch-Regué Dalia , Tenorio Raquel , Fernández de Castro Isabel , Perez -Zsolt Daniel , Muñoz-Basagoiti Jordana , Sachse Martin , Fernández-Sánchez Sara Y. , Gallemí Marçal , Ortega-González Paula , Fernández-Oliva Alberto , Gabaldón José A. , Nuñez-Delicado Estrella , Casas Josefina , Tarrés Ferran , Alert Júlia-Vergara , Segalés Joaquim , Carillo Jorge , Blanco Julià , Sala Bonaventura Clotet , Cerón-Carrasco José P. , Izquierdo-Useros Nuria , Risco Cristina
Published: November 2022

The SARS-CoV-2 pandemic made evident that we count with few coronavirus-fighting drugs. Here we aimed to identify a cost-effective antiviral with broad spectrum activity and high safety and tolerability profiles. We began elaborating a list of 116 drugs previously used to treat other pathologies or characterized in pre-clinical studies with potential to treat coronavirus infections. We next employed molecular modelling tools to rank the 44 most promising inhibitors and tested their efficacy as antivirals against a panel of α and β coronavirus, e.g., the HCoV-229E and SARS-CoV-2 viruses. Four drugs, OSW-1, U18666A, hydroxypropyl-β-cyclodextrin (HβCD) and phytol, showed antiviral activity against both HCoV-229E (in MRC5 cells) and SARS-CoV-2 (in Vero E6 cells). The mechanism of action of these compounds was studied by transmission electron microscopy (TEM) and by testing their capacity to inhibit the entry of SARS-CoV-2 pseudoviruses in ACE2-expressing HEK-293T cells. The entry was inhibited by HβCD and U18666A, yet only HβCD could inhibit SARS-CoV-2 replication in the pulmonary cells Calu-3. With these results and given that cyclodextrins are widely used for drug encapsulation and can be safely administered to humans, we further tested 6 native and modified cyclodextrins, which confirmed β-cyclodextrins as the most potent inhibitors of SARS-CoV-2 replication in Calu-3 cells. All accumulated data points to β-cyclodextrins as promising candidates to be used in the therapeutic treatments for SARS-CoV-2 and possibly other respiratory viruses.
Crystal structure of Sphingobacterium multivorum serine palmitoyltransferase complexed with tris(hydroxymethyl)aminomethane
Authors: Ikushiro Hiroko , Takahashi Aya , Murakami Taiki , Katayama Asuka , Sawai Taiki , Goto Haruna , Miyahara Ikuko , Kamiya Nobuo , Yano Takato
Published: November 2022

Serine palmitoyltransferase (SPT) catalyses the first reaction in sphingolipid biosynthesis: the decarboxylative condensation of L-serine (L-Ser) and palmitoyl-CoA to form 3-ketodihydrosphingosine. SPT from Sphingobacterium multivorum has been isolated and its crystal structure in complex with L-Ser has been determined at 2.3 Å resolution (PDB entry 3a2b). However, the quality of the crystal was not good enough to judge the conformation of the cofactor molecule and the orientations of the side chains of the amino-acid residues in the enzyme active site. The crystal quality was improved by revision of the purification procedure and by optimization of both the crystallization procedure and the post-crystallization treatment conditions. Here, the crystal structure of SPT complexed with tris(hydroxymethyl)aminomethane (Tris), a buffer component, was determined at 1.65 Å resolution. The protein crystallized at 20°C and diffraction data were collected from the crystals to a resolution of 1.65 Å. The crystal belonged to the tetragonal space group P41212, with unit-cell parameters a = b = 61.32, c = 208.57 Å. Analysis of the crystal structure revealed C4—C5—C5A—O4P (77°) and C5—C5A—O4P—P (–143°) torsion angles in the phosphate-group moiety of the cofactor pyridoxal 5′-phosphate (PLP) that are more reasonable than those observed in the previously reported crystal structure (14° and 151°, respectively). Furthermore, the clear electron density showing a Schiff-base linkage between PLP and the bulky artificial ligand Tris indicated exceptional flexibility of the active-site cavity of this enzyme. These findings open up the possibility for further study of the detailed mechanisms of substrate recognition and catalysis by this enzyme.
Determinants of user's intentions to book hotels: a comparison of websites and mobile apps
Authors: Ali Faizan , Ali Laiba , Gao Zhaoyu , Terrah Abraham , Turktarhan Gozde
Published: November 2022

Purpose

This empirical study uses the stimulus-organism-response (S-O-R) framework to examine the interrelationships amongst hotel websites and app quality, flow, telepresence, user engagement and booking intentions.

Design/methodology/approach

Data from two different datasets, including users of hotel websites (N sample 1 = 257) and hotel mobile apps (N sample 2 = 292), were collected. Partial least squares (PLS-SEM) was used to test the research model.

Findings

Findings indicate that the quality of the hotel websites and mobile apps positively influences telepresence, flow and engagement. Telepresence and flow positively affect the users booking intentions for both the samples. However, for hotel website users, engagement has a no-significant effect on booking intentions. Finally, telepresence has a non-significant effect on flow, and flow has a non-significant effect on engagement for both the users of hotel websites and mobile apps.

Originality/value

This study uses two datasets to understand how hotel booking channel (hotel website and mobile app) quality leads to booking intentions by tapping into telepresence, flow and engagement.
Exploring the adoption of technology against delays in construction projects
Authors: Gurgun Asli Pelin , Koc Kerim , Kunkcu Handan
Published: November 2022

Purpose

Completing construction projects within the planned schedule has widely been considered as one of the major project success factors. This study investigates the use of technologies to address delays in construction projects and aims to address three research questions (1) to identify the adopted technologies and proposed solutions in the literature, (2) to explore the reasons why the delays cannot be prevented despite disruptive technologies and (3) to determine the major strategies to prevent delays in construction projects.

Design/methodology/approach

In total, 208 research articles that used innovative technologies, methods, or tools to avoid delays in construction projects were investigated by conducting a comprehensive literature review. An elaborative content analysis was performed to cover the implemented technologies and their transformation, highlighted research fields in relation to selected technologies, focused delay causes and corresponding delay mitigation strategies and emphasized project types with specific delay causes. According to the analysis results, a typological framework with appropriate technological means was proposed.

Findings

The findings revealed that several tools such as planning, imaging, geo-spatial data collection, machine learning and optimization have widely been adopted to address specific delay causes. It was also observed that strategies to address various delay causes throughout the life cycle of construction projects have been overlooked in the literature. The findings of the present research underpin the trends and technological advances to address significant delay causes.

Originality/value

Despite the technological advancements in the digitalization era of Industry 4.0, many construction projects still suffer from poor schedule performance. However, the reason of this is questionable and has not been investigated thoroughly.
Academic performance and work placements: does academic performance influence the decision to complete a work placement?
Authors: McCann Michael , Hewitt Michael
Published: November 2022

Purpose

There is strong evidence that year-long work placements make students more employable and produces better academic performance. Despite this, UK participation rates remain stubbornly low. The authors examine the influence of academic performance on students' willingness and ability to complete work placements.

Design/methodology/approach

This study’s novel conceptual framework distinguishes students by their intentions regarding work placements indicated at enrolment as well as whether they completed a work placement. The authors use a sample of 226 business and economics students, employing propensity score weighted multiple regression to analyse the influence of academic performance.

Findings

The results indicate that academic performance has a significant influence on the decision to include a work placement option at enrolment. For those students who do pursue work placements, first-year academic performance had a significantly positive impact on their ability to secure a placement job. Finally, completion of a work placement was beneficial to final year academic performance.

Practical implications

Work placements are beneficial. Since low academic performance deters students from pursuing such opportunities, universities may need to communicate the benefits better to encourage greater interest. Further, universities need to realistically manage the expectations of students with low academic performance who want to do work placements and provide targeted support during the application process. Furthermore, alternatives to work placements should be provided.

Originality/value

This research adds to the literature investigating the influence of academic performance through academic self-concept on students' investment decisions to include a work placement in their degree study and in students' ability to secure a work placement.
Challenges facing procurement and supply professions in Tanzania: higher education students' perceptions
Authors: Changalima Ismail Abdi , Mwaiseje Shadrack Samwel , Mchopa Alban Dismas , Panga Faustine Peter
Published: November 2022

Purpose

Despite the fact that students in higher education contributes significantly to the number of professionals, little has been done to incorporate the students’ perspectives on the status of procurement and supply professions in Tanzania. This study examined the challenges confronting the procurement and supply professions from the perspective of future procurement professionals enrolled in Tanzanian higher education.

Design/methodology/approach

A cross-sectional design was used to collect data from undergraduate students majoring in procurement and supply chain management in Tanzanian higher education using a structured questionnaire.

Findings

The findings revealed that the challenges affecting the procurement and supply professions were buyer- and supplier-related challenges as perceived by Tanzanian higher education students.

Research limitations/implications

The study's findings should be generalized with caution because the findings represent the perspectives of Tanzanian procurement and supply undergraduate business students. Furthermore, the included sample of procurement and supply undergraduates cannot represent all students' perceptions; thus, other studies may broaden the sample by including the opinions of other higher education students.

Originality/value

This is the first study that looks at how students in higher education institutions, who are considered future procurement and supply professionals, perceive the challenges of the procurement and supply professions in Tanzania.
Speaking up as an extension of socio-cultural dynamics in hospital settings: a study of staff experiences of speaking up across seven hospitals
Authors: Pavithra Antoinette , Mannion Russell , Sunderland Neroli , Westbrook Johanna
Published: November 2022

Purpose

The study aimed to understand the significance of how employee personhood and the act of speaking up is shaped by factors such as employees' professional status, length of employment within their hospital sites, age, gender and their ongoing exposure to unprofessional behaviours.

Design/methodology/approach

Responses to a survey by 4,851 staff across seven sites within a hospital network in Australia were analysed to interrogate whether speaking up by hospital employees is influenced by employees' symbolic capital and situated subjecthood (SS). The authors utilised a Bourdieusian lens to interrogate the relationship between the symbolic capital afforded to employees as a function of their professional, personal and psycho-social resources and their self-reported capacity to speak up.

Findings

The findings indicate that employee speaking up behaviours appear to be influenced profoundly by whether they feel empowered or disempowered by ongoing and pre-existing personal and interpersonal factors such as their functional roles, work-based peer and supervisory support and ongoing exposure to discriminatory behaviours.

Originality/value

The findings from this interdisciplinary study provide empirical insights around why culture change interventions within healthcare organisations may be successful in certain contexts for certain staff groups and fail within others.
The (commercialised) experience of operating: Embodied preferences, ambiguous variations and explaining widespread patient harm
Authors: Ducey Ariel , Donoso Claudia , Ross Sue , Robert Magali
Published: November 2022

This article provides a detailed account of how surgeons perceived and used a device‐procedure that caused widespread patient harm: transvaginal mesh for the treatment of pelvic floor disorders in women. Drawing from interviews with 27 surgeons in Canada, the UK, the United States and France and observations of major international medical conferences in North America and Europe between 2015 and 2018, we describe the commercially driven array of operative variations in the use of transvaginal mesh and show that surgeons’ understanding of their hands‐on, sensory experience with these variations is central to explaining patient harm. Surgeons often developed preferences for how to manage actual and anticipated dangers of transvaginal mesh procedures through embodied operative adjustments, but collectively the meaning of these preferences was fragmented, contested and deferred. We critically reflect on surgeons’ understandings of their operative experience, including the view that such experience is not evidence. The harm in this case poses a challenge to some ways of thinking about uncertainty and errors in medical sociology, and calls for attention to a specific feature of surgical work: the extent and persistence of operative practices that elude classification as right or wrong but are still most certainly better and worse.
Phase II study of durvalumab (MEDI 4736) plus carboplatin and etoposide in elderly patients with extensive stage small cell lung cancer: Study protocol of turtle study (LOGIK 2003)
Authors: Ishii Hidenobu , Azuma Koichi , Shimose Takayuki , Yoshioka Hiroshige , Kurata Takayasu , Shingu Naoki , Okamoto Masaki , Kawashima Yosuke , Okamoto Isamu
Published: November 2022

Background

Recently, the addition of antiprogrammed cell death‐ligand 1 (PD‐L1) monoclonal antibodies, including durvalumab and atezolizumab to platinum‐based chemotherapy, has demonstrated clinical benefits in patients with untreated advanced small cell lung cancer (SCLC). However, these clinical trials comprised small populations of elderly patients with SCLC. Therefore, the safety of anti‐PD‐L1 immunotherapy plus platinum and etoposide in elderly patients remains unclear.

Methods

This prospective, multicenter, single‐arm study was designed to evaluate the safety and efficacy of durvalumab plus carboplatin and etoposide in untreated elderly patients (aged > 75) with extensive stage (ES) SCLC. A total of 40 patients were recruited. Patients received up to four cycles of durvalumab 1500 mg and carboplatin at a dose equivalent to an area under the curve of 5 on day 1, and etoposide 80 mg/m2 on days 1 to 3 every 3 weeks as induction treatment, followed by durvalumab maintenance treatment every 4 weeks. The primary endpoint was safety as measured by adverse events according to the Common Terminology Criteria for Adverse Events version 5.0, laboratory analyses, vital signs, and physical examination. Key secondary endpoints were objective response rate, median progression‐free survival, 12‐month overall survival rate, and the completion rate for four cycles of induction chemotherapy.

Discussion

The present study was designed to evaluate the safety of durvalumab plus carboplatin and etoposide in elderly patients with ES‐SCLC.
Environmental enrichment alleviates cognitive and psychomotor alterations and increases adult hippocampal neurogenesis in cocaine withdrawn mice
Authors: Mañas‐Padilla M. Carmen , Tezanos Patricia , Cintado Elisa , Vicente Lucía , Sánchez‐Salido Lourdes , Gil‐Rodríguez Sara , Trejo José L. , Santín Luis J. , Castilla‐Ortega Estela
Published: November 2022

Cocaine is a widely used psychostimulant drug whose repeated exposure induces persistent cognitive/emotional dysregulation, which could be a predictor of relapse in users. However, there is scarce evidence on effective treatments to alleviate these symptoms. Environmental enrichment (EE) has been shown to be associated with improved synaptic function and cellular plasticity changes related to adult hippocampal neurogenesis (AHN), resulting in cognitive enhancement. Therefore, EE could mitigate the negative impact of chronic administration of cocaine in mice and reduce the emotional and cognitive symptoms present during cocaine abstinence. In this study, mice were chronically administered with cocaine for 14 days, and control mice received saline. After the last cocaine or saline dose, mice were submitted to control or EE housing conditions, and they stayed undisturbed for 28 days. Subsequently, mice were evaluated with a battery of behavioural tests for exploratory activity, emotional behaviour, and cognitive performance. EE attenuated hyperlocomotion, induced anxiolytic‐like behaviour and alleviated cognitive impairment in spatial memory in the cocaine‐abstinent mice. The EE protocol notably upregulated AHN in both control and cocaine‐treated mice, though cocaine slightly reduced the number of immature neurons. Altogether, these results demonstrate that EE could enhance hippocampal neuroplasticity ameliorating the behavioural and cognitive consequences of repeated administration of cocaine. Therefore, environmental stimulation may be a useful strategy in the treatment cocaine addiction.
A fear‐based view of wisdom: The role of leader fear of failure and psychological empowerment
Authors: Solansky Stephanie T. , Wang Yuan , Quansah Emmanuel
Published: November 2022

Leader wisdom is crucial to effective organizations because it is one of the greatest human capacities. However, understanding what factors impact leader wisdom is still developing. In this paper, we rely on a fear‐based view of wisdom and empirically examine through a quantitative study of 249 leaders if one of the primary regulators of human behavior (fear) is positively related to wisdom. We are specifically focused on the role of fear of failure and wisdom. Additionally, because we recognize that fear has a negative connotation and has a tipping point regarding leader effectiveness, we propose that psychological empowerment serves as a coping mechanism for fear and mediates the relationship between fear of failure and wisdom. Through structural equation modeling (SEM), we demonstrate that fear of failure does positively impact leader wisdom and that this relationship is mediated by psychological empowerment. This study contributes to the literature by advancing the fear‐based view of wisdom which unites two of the most powerful concepts in human history: fear and wisdom. Although wisdom has a resurgence of interest in business literature, fear is not given much attention. By theoretically and empirically linking fear of failure with wisdom, we shed light on how fear is an important motivating mechanism. The study also contributes to practice by suggesting leaders should fear failure and avoid minimizing fears to be wise.
Absence of copy number gain ofEGFR: A possible predictive marker of long‐term response to afatinib
Authors: Nakamura Tomomi , Sato Akemi , Nakashima Chiho , Abe Tomonori , Iwanaga Kentaro , Umeguchi Hitomi , Kawaguchi Atsushi , Sueoka‐Aragane Naoko
Published: November 2022

Treatment efficacy of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI) is diverse even in non‐small cell lung cancer (NSCLC) patients withEGFRactivating mutations. Extraordinary long‐term responses sustained over 3 years among NSCLC patients treated with afatinib, an EGFR‐TKI, have been reported, but how to predict such long survivors has not been clarified. A multi‐institutional prospective observational study, based on comprehensive genomic examination performed with next‐generation sequencing of circulating tumor DNA (ctDNA), was conducted to identify potential predictive markers of long‐term response to afatinib. Twenty‐nine patients with advanced stage NSCLC andEGFRdriver mutations detected by standard techniques were enrolled in the study. ctDNA from plasma collected before afatinib treatment was analyzed by Guardant360. ctDNA was detected in 25 of the 29 samples. Median progression‐free survival was shorter in patients whose tumors hadEGFRcopy number gain (7.0vs23.0 months,p = 0.022). The impact ofEGFRcopy number on cell proliferation and the antitumor effect of afatinib were evaluated using genome‐editing lung cancer cell lines. HCC827 withEGFRamplification was relatively resistant to afatinib at concentrations below 0.5 nM, but genome‐edited derivatives of HCC827 with decreasedEGFRcopy number demonstrated growth inhibition with 0.1 nM afatinib. The absence ofEGFRcopy number gain detected in ctDNA may be a predictive marker of long‐term response to afatinib. Comprehensive genomic analysis could lead to a more accurate prediction of EGFR‐TKI efficacy.
Topical eye medications causing allergic contact dermatitis
Authors: Ahlström Malin Glindvad , Skov Lone , Heegaard Steffen , Zachariae Claus , Garvey Lene Heise , Johansen Jeanne Duus
Published: November 2022

Background

Allergic contact dermatitis (ACD) in the eye region caused by topical eye medications is difficult to diagnose and may be overlooked.

Objective

To study the characteristics and causative agents in patients with ACD caused by topical eye medications in a Danish tertiary dermatology department.

Methods

A retrospective study of 318 patients, patch tested between 2013 and 2021 due to suspected ACD to topical eye medications. All patients were tested with a locally developed eye medication series, some were additionally tested with suspected eye medications. Medical records were studied in patch test positive patients.

Results

Contact allergy to a topical eye allergen/medication was found in 12.9% (n = 41) of 318 patients, and culprit allergens were phenylephrine (6.9%), timolol (2.5%) and ketotifen (1.6%). Patch test positive patients were often previously diagnosed with cataract (29.3%) or glaucoma (24.4%), and the majority reported more than one previous reaction. Initial symptoms were oedema (56.0%), erythema (48.8%) and dermatitis (31.7%) in the eye region, and facial dermatitis was also seen.

Conclusions

Patients with symptoms from the eye region who have been using topical eye medications should be patch tested with ingredients from commonly used eye medications supplemented by the products tested ‘as is’.
Assessing the interaction between L‐dopa and γ‐transcranial alternating current stimulation effects on primary motor cortex plasticity in Parkinson's disease
Authors: Guerra Andrea , D'Onofrio Valentina , Asci Francesco , Ferreri Florinda , Fabbrini Giovanni , Berardelli Alfredo , Bologna Matteo
Published: November 2022

L‐dopa variably influences transcranial magnetic stimulation (TMS) parameters of motor cortex (M1) excitability and plasticity in Parkinson's disease (PD). In patients OFF dopaminergic medication, impaired M1 plasticity and defective GABA‐A‐ergic inhibition can be restored by boosting gamma (γ) oscillations via transcranial alternating current stimulation (tACS) during intermittent theta‐burst stimulation (iTBS). However, it is unknown whether L‐dopa modifies the beneficial effects of iTBS‐γ‐tACS on M1 in PD. In this study, a PD patients group underwent combined iTBS‐γ‐tACS and iTBS‐sham‐tACS, each performed both OFF and ON dopaminergic therapy (four sessions in total). Motor evoked potentials (MEPs) elicited by single TMS pulses and short‐interval intracortical inhibition (SICI) were assessed before and after iTBS‐tACS. We also evaluated possible SICI changes during γ‐tACS delivered alone in OFF and ON conditions. The amplitude of MEP elicited by single TMS pulses and the degree of SICI inhibition significantly increased after iTBS‐γ‐tACS. The amount of change produced by iTBS‐γ‐tACS was similar in patients OFF and ON therapy. Finally, γ‐tACS (delivered alone) modulated SICI during stimulation and this effect did not depend on the dopaminergic condition of patients. In conclusion, boosting cortical γ oscillatory activity via tACS during iTBS improved M1 plasticity and enhanced GABA‐A‐ergic transmission in PD patients to the same extent regardless of dopaminergic state. These results suggest a lack of interaction between L‐dopa and γ‐tACS effects at the M1 level. The possible neural substrate underlying iTBS‐γ tACS effects, that is, γ‐resonant GABA‐A‐ergic interneurons activity, may explain our findings.
Reliability of corticospinal excitability and intracortical inhibition in biceps femoris during different contraction modes
Authors: Presland Joel D. , Tofari Paul J. , Timmins Ryan G. , Kidgell Dawson J. , Opar David A.
Published: November 2022

This study aimed to determine the test–retest reliability of a range of transcranial magnetic stimulation (TMS) outcomes in the biceps femoris during isometric, eccentric and concentric contractions. Corticospinal excitability (active motor threshold 120% [AMT120%] and area under recruitment curve [AURC]), short‐ and long‐interval intracortical inhibition (SICI and LICI) and intracortical facilitation (ICF) were assessed from the biceps femoris in 10 participants (age 26.3 ± 6.0 years; height 180.2 ± 6.6 cm, body mass 77.2 ± 8.0 kg) in three sessions. Single‐ and paired‐pulse stimuli were delivered under low‐level muscle activity (5% ± 2% of maximal isometric root mean squared surface electromyography [rmsEMG]) during isometric, concentric and eccentric contractions. Participants were provided visual feedback on their levels of rmsEMG during all contractions. Single‐pulse outcomes measured during isometric contractions (AURC, AMT110%, AMT120%, AMT130%, AMT150%, AMT170%) demonstrated fair to excellent reliability (ICC range, .51 to .92; CV%, 21% to 37%), whereas SICI, LICI and ICF demonstrated good to excellent reliability (ICC range, .62 to .80; CV%, 19 to 42%). Single‐pulse outcomes measured during concentric contractions demonstrated excellent reliability (ICC range, .75 to .96; CV%, 15% to 34%), whereas SICI, LICI and ICF demonstrated good to excellent reliability (ICC range, .65 to .76; CV%, 16% to 71%). Single‐pulse outcomes during eccentric contractions demonstrated fair to excellent reliability (ICC range, .56 to .96; CV%, 16% to 41%), whereas SICI, LICI and ICF demonstrated good to excellent (ICC range, .67 to .86; CV%, 20% to 42%). This study found that both single‐ and paired‐pulse TMS outcomes can be measured from the biceps femoris muscle across all contraction modes with fair to excellent reliability. However, coefficient of variation values were typically greater than the smallest worthwhile change which may make tracking physiological changes in these variables difficult without moderate to large effect sizes.
Regulatory mechanisms of HMGB1 and its receptors in polycystic ovary syndrome‐driven gravid uterine inflammation
Authors: Hu Min , Zhang Yuehui , Lu Yaxing , Han Jing , Guo Tingting , Cui Peng , Brännström Mats , Shao Linus R. , Billig Håkan
Published: November 2022

High‐mobility group box 1 (HMGB1) is critical for inflammatory homeostasis and successful pregnancy, and there is a strong association among elevated levels of HMGB1, polycystic ovary syndrome (PCOS), chronic inflammation and pregnancy loss. However, the mechanisms responsible for PCOS‐driven regulation of uterine HMGB1 and its candidate receptors [toll‐like receptor (TLR) 2 and 4] and inflammatory responses during pregnancy remain unclear. In this study, we found a gestational stage‐dependent decrease in uterine HMGB1 and TLR4 protein abundance in rats during normal pregnancy. We demonstrated that increased expression of HMGB1, TLR2 and TLR4 proteins was associated with activation of inflammation‐related signalling pathways in the gravid uterus exposed to 5α‐dihydrotestosterone and insulin, mimicking the clinical features (hyperandrogenism and insulin resistance) of PCOS and this elevation was completely inhibited by treatment with the androgen receptor (AR) antagonist flutamide. Interestingly, acute exposure to lipopolysaccharide suppressed HMGB1, TLR4 and inflammation‐related protein abundance but did not affect androgen levels or AR expression in the gravid uterus with viable fetuses. Furthermore, immunohistochemical analysis revealed that, in addition to being localized predominately in the nuclear compartment, HMGB1 immunoreactivity was also detected in the cytoplasm in the PCOS‐like rat uterus, PCOS endometrium and pregnant rat uterus with haemorrhagic and resorbed fetuses, possibly via activation of nuclear factor κB signalling. These results suggest that both AR‐dependent and AR‐independent mechanisms contribute to the modulation of HMGB1/TLR2/TLR4‐mediated uterine inflammation. We propose that the elevation of HMGB1 and its receptors and disruption of the pro‐/anti‐inflammatory balance in the gravid uterus may participate in the pathophysiology of PCOS‐associated pregnancy loss.
Ban‐1 Zircon: A New Natural Zircon Reference Material for LA‐MC‐ICP‐MS Zr and Hf Isotopic Determinations
Authors: Xie Jin‐Cheng , Zhu Di‐Cheng , Wang Qing , Zhang Liang‐Liang , Cong Feng , Nie Fei , Lu Ying‐Huai , Liu Li
Published: November 2022

New zircon reference materials for in situ zircon radiogenic Hf isotope and stable Zr isotopic determinations made by laser ablation multi‐collector inductively coupled plasma‐mass spectrometry (LA‐MC‐ICP‐MS) are required due to high data productivity and consequently high reference material consumption rate. This study examines a new natural zircon for Zr isotope ratios by double spike thermal ionisation mass spectrometry (TIMS), and for Hf isotopes by bulk solution nebuliser (SN)‐MC‐ICP‐MS with both Zr and Hf determined by LA‐MC‐ICP‐MS. A total of five zirconium isotope measurements from drilled zircons, determined by TIMS, yield a mean δ94/90ZrIPGP‐Zr value of ‐0.09 ± 0.06‰ (2s). Five and eight hafnium isotope measurements for powders from the drilled zircons and Ban‐1‐4 by SN‐MC‐ICP‐MS, yield mean 176Hf/177Hf ratios of 0.282985 ± 0.000011 (2s) and 0.282982 ± 0.000007 (2s), respectively. The mean δ94/90ZrIPGP‐Zr value and 176Hf/177Hf ratio determined by LA‐MC‐ICP‐MS analyses are ‐0.06 ± 0.09‰ (2s, n = 504) and 0.282985 ± 0.000035 (2s, n = 327), respectively. The isotopic homogeneities suggest that the Ban‐1 zircon is a suitable reference material for microbeam Zr and Hf isotopic measurements.
The Factor H protein family: The switchers of the complement alternative pathway
Authors: Lucientes‐Continente Laura , Márquez‐Tirado Bárbara , Goicoechea de Jorge Elena
Published: November 2022

The factor H (FH) protein family is emerging as a complex network of proteins controlling the fate of the complement alternative pathway (AP) and dictating susceptibility to a wide range of diseases including infectious, inflammatory, autoimmune, and degenerative diseases and cancer. Composed, in man, of seven highly related proteins, FH, factor H‐like 1, and 5 factor H‐related proteins, some of the FH family proteins are devoted to down‐regulating the AP, while others exert an opposite function by promoting AP activation. Recent findings have provided insights into the molecular mechanisms defining their biological roles and their pathogenicity, illustrating the relevance that the balance between the regulators and the activators within this protein family has in defining the outcome of complement activation on cell surfaces. In this review we will discuss the emerging roles of the factor H protein family, their impact in the complement cascade, and their involvement in the pathogenesis of complement‐mediated diseases associated with the AP dysregulation.
What aspects of counting help infants attend to numerosity?
Authors: Wang Jinjing (Jenny) , Feigenson Lisa
Published: November 2022

Recent work shows that 18‐month old infants understand that counting is numerically relevant—infants who see objects counted are more likely to represent the approximate number of objects in the array than infants who see the objects labeled but not counted. Which aspects of counting signal infants to attend to numerosity in this way? Here we asked whether infants rely on familiarity with the count words in their native language, or on procedures instantiated by the counting routine, independent of specific tokens. In three experiments (N = 48), we found that 18‐month old infants from English‐speaking households successfully distinguished four hidden objects from two when the objects were counted correctly, regardless of their familiarity with the count words (i.e., when objects were counted in familiar English and in unfamiliar German). However, when the objects were counted using familiar English count words in ways that violated basic counting principles, infants no longer represented the arrays, failing to distinguish four hidden objects from two. Together with previous findings, these results suggest that children may link the procedure of counting with numerosity years before they learn the meanings of the count words.
Investigating the causal effect of cognition on the self‐reported loss of functional dentition using marginal structural models: The Panel on Health and Ageing of Singaporean Elderly study
Authors: Peres Marco A. , Peres Karen G. , Chan Angelique , Wu Bei , Mittinty Murthy
Published: November 2022

Aim

To assess the effect of cognition on the loss of functional dentition.

Materials and Methods

We used data from the three waves of the Panel on Health and Ageing of Singaporean Elderly study (n = 4990 at baseline, 774 complete cases analysed) over 6 years (2009–2015). The outcome was the loss of functional dentition (<21 teeth). The exposure was cognitive impairment, while baseline confounders included age, sex, education, and ethnicity. Time‐varying confounders included income, living arrangements, smoking, diabetes, depressive symptoms, cardiovascular disease, and body mass index. We used marginal structural mean models with inverse probability treatment weighted.

Results

The mean age of the participants was 70.2 years at baseline. The proportion of participants with loss of functional dentition increased from 74.6% to 89.9% over 6 years. Women, ethnic Chinese, less educated, smokers, people with diabetes, and individuals with depression had a higher proportion of loss of functional dentition than their counterparts. Loss of functional dentition was 1.8 times higher (odds ratio 1.80; 95% confidence interval 0.88–3.69) among those with cognitive impairment after taking well‐known confounders into account.

Conclusions

After accounting for the time‐varying exposure and confounding evidence, the association between cognition and functional dentition among the elderly in Singapore remains uncertain.
Prevalence and implications of type D personality in patients with alopecia areata: A marker of quality‐of‐life impairment and mood status disturbances, a comparative study
Authors: Sánchez‐Díaz Manuel , Montero‐Vílchez Trinidad , Cuenca‐Barrales Carlos , Molina‐Leyva Alejandro , Arias‐Santiago Salvador
Published: November 2022

Introduction

Distressed personality (or Type D personality, TDp) is a personality trait that has been associated with poor quality of life in patients suffering from a variety of skin diseases such as psoriasis or urticaria. To date the potential association between Alopecia areata (AA) and TDp has not been studied. The aim of this study was to compare the prevalence of TDp between patients with AA and controls, and to analyse the impact of TDp on patients with AA regarding mood status disturbances, quality of life and sexuality.

Methods

Cross‐sectional study includes patients suffering from mild‐to‐severe AA and sex‐ and age‐matched healthy controls. Socio‐demographic and clinical variables, quality of life, sexual disfunction, anxiety, depression and TDp were collected using validated questionnaires.

Results

A total of 120 participants (60 patients and 60 controls) were included. Patients with AA showed higher prevalence of TDp than controls (35% vs. 15% p = 0.01), as well as higher rates of anxiety, depression and sexual dysfunction (p < 0.05). TDp was found to be linked to disease severity (p = 0.04), anxiety and depression scores (p < 0.001) and worse quality of life (p = 0.001). No relationship was found between TDp and sexual dysfunction.

Discussion

Type D personality prevalence is higher in patients with AA than in controls. It is associated with higher rates of anxiety, depression and worse quality of life. Screening for this type of personality could be useful to detect patients who could benefit from additional psychological support as a complement to their medical treatment.