bluuebunny/crossref_metadata_2025 huggingface dataset:
3D-printed capillaric ELISA-on-a-chip with aliquoting
Authors: Parandakh Azim , Ymbern Oriol , Jogia Will , Renault Johan , Ng Andy , Juncker David
Published: September 2022

Sandwich immunoassays such as the enzyme-linked immunosorbent assay (ELISA) have been miniaturized and performed in a lab-on-a-chip format, but the execution of the multiple assay steps typically requires a computer or complex peripherals. Recently, an ELISA for detecting antibodies was encoded structurally in a chip thanks to the microfluidic chain reaction but the need for precise pipetting and intolerance to commonly used surfactant concentrations limited the potential for broader adoption. Here, we introduce the ELISA-on-a-chip with aliquoting functionality that obviates the need for precise pipetting, accommodates higher surfactant concentrations, includes barrier channels that delay the contact between solutions and prevent undesired mixing, and that executed a quantitative, high sensitivity assay for the SARS-CoV-2 nucleocapsid protein in 4×-diluted saliva. Upon loading the chip using disposable pipettes, capillary flow draws each reagent and the sample into a separate volumetric measuring reservoir for detection antibody (70 µL), enzyme conjugate (50 µL), substrate (80 µL), and sample (210 µL), and splits washing buffer into 4 different reservoirs of 40, 40, 60, and 20 µL. The excess volume is autonomously drained via a structurally encoded capillaric aliquoting circuit, creating aliquots with an accuracy of >93%. Next, the user click-connects the assay module, comprising a nitrocellulose membrane with immobilized capture antibodies and a capillary pump, to the chip which triggers the step-by-step, timed flow of all aliquoted solutions. A colored precipitate forming a line on a nitrocellulose strip serves as an assay readout, and upon digitization, yielded a binding curve with a limit of detection of 54 and 91 pg/mL for buffer and diluted saliva respectively, vastly outperforming rapid tests. The ELISA chip is 3D-printed, modular, adaptable to other targets and assays, and could be used to automate ELISA in the lab; or as a diagnostic test at the point of care with the convenience and form factor of rapid tests while preserving the protocol and performance of central laboratory ELISA.
Engineering non-cytotoxic delivery of proteins by T cells via fusion to NPC2
Authors: Saeedi Arash , Bandey Irfan N. , Leekha Ankita , Fathi Mohsen , Rezvan Ali , Montalvo Melisa J. , Wu Kwan-Ling , Bohat Ritu , Peng Weiyi , Varadarajan Navin
Published: September 2022

Engineering cellular therapeutics by programming T cells has great potential in immunology. The primary mechanism employed by T cells for the specific transfer of proteins at the immunological synapse is via the lysosomal perforin pathway that facilitates the transfer of cytotoxic granzymes leading to apoptosis in target cells. Facilitating the delivery of non-cytotoxic proteins through perforin oligomers will dramatically expand the range of protein cargos that T cells can traffic to the target cells. Here, we have identified the intralysosomal protein, NPC2, as a chaperone that can facilitate the delivery of T-cell derived reporter proteins through perforin pores at the immunological synapse. Structural and biophysical considerations suggested that NPC2 could traverse through perforin pores and in vitro experiments confirmed the transport of purified NPC2 through perforin pores on cell membranes. To characterize the ability of NPC2 to facilitate the transfer of payloads in T cells, we constructed NPC2-mCherry fusion proteins in T cells. Using confocal microscopy and flow cytometry, we confirmed the colocalization of the NPC2 fused protein with lytic granules and the transfer of the fluorescent protein payload from T cells to target cells in co-culture experiments. The NPC2 fusion enabled the localization of mCherry to secretory lysosomes in mouse TCR CD8+ T cells and human CD4+ and CD8+ chimeric antigen receptor (CAR) T cells. These results illustrate that by using NPC2 as a molecular chaperone, the NPC2-perforin pathway can be exploited as a programmable molecular delivery system for cell-based therapies.
Small-molecule ketone esters treat brain network abnormalities in an Alzheimer’s disease mouse model
Authors: Newman John C. , Ma Keran , Kroll François , Higgins Erin , Ulrich Scott , Palop Jorge J. , Verdin Eric
Published: September 2022

Altered brain network activity and the resulting hypersynchrony are important for the pathogenesis of cognitive decline in Alzheimer’s disease (AD) mouse models. Treatments that reduce epileptiform discharges (EDs) or network hyperactivity improve cognition in AD models and humans. We first show that ketogenic diet, but not fasting, rapidly and persistently reduced EDs in the hAPPJ20 Alzheimer’s mouse model over timescales of hours to months. Then, to identify the specific mechanism of the pleiotropic ketogenic diet, we developed small molecule ketone esters to deliver ketone bodies pharmacologically. Two ketone esters recapitulate ED suppression without other dietary manipulation, over time scales of minutes to one week. This small molecule rescue was associated with reduced low-frequency oscillatory activity similar to the recently reported mechanism of an NMDA receptor modulator molecule in this model. Long-term KD resulted in cognitive improvement and in a sex-stratified analysis also improved survival in the more severely affected hAPPJ20 males. Agents that deliver ketone bodies via small molecules or act on downstream targets may hold therapeutic promise in AD through the mechanism of improved network function and reduced epileptiform activity.
Comparative structural analyses of the NHL domains from the human E3 ligase TRIM–NHL family
Authors: Chaikuad Apirat , Zhubi Rezart , Tredup Claudia , Knapp Stefan
Published: September 2022

Tripartite motif (TRIM) proteins constitute one of the largest subfamilies of the RING-type E3 ubiquitin ligases that play a role in diverse processes from homeostasis and immune response to viral restriction. While TRIM proteins typically harbor an N-terminal RING finger, a B-box and a coiled-coil domain, a high degree of diversity lies in their C termini that contain diverse protein interaction modules, most of which, both structures and their roles in intermolecular interactions, remain unknown. Here, high-resolution crystal structures of the NHL domains of three of the four human TRIM–NHL proteins, namely TRIM2, TRIM3 and TRIM71, are presented. Comparative structural analyses revealed that, despite sharing an evolutionarily conserved six-bladed β-propeller architecture, the low sequence identities resulted in distinct properties of these interaction domains at their putative binding sites for macromolecules. Interestingly, residues lining the binding cavities represent a hotspot for genetic mutations linked to several diseases. Thus, high sequence diversity within the conserved NHL domains might be essential for differentiating binding partners among TRIM–NHL proteins.
Purification, crystallization and crystallographic analysis of the PorX response regulator associated with the type IX secretion system
Authors: Saran Anshu , Weerasinghe Nuwani , Thibodeaux Christopher J. , Zeytuni Natalie
Published: September 2022

Pathogenic bacteria utilize specialized macromolecular secretion systems to transport virulence factors across membrane(s) and manipulate their infected host. To date, 11 secretion systems have been identified, including the type IX secretion system (T9SS) associated with human, avian and farmed-fish diseases. As a bacterial secretion system, the T9SS also facilitates gliding motility and the degradation of different macromolecules by the secretion of metabolic enzymes in nonpathogenic bacteria. PorX is a highly conserved protein that regulates the transcription of essential T9SS components and additionally mediates the function of T9SS via direct interaction with PorL, the rotary motor protein of the T9SS. PorX is also a member of a two-component system regulatory cascade, where it serves as the response regulator that relays a signal transduced from a conserved sensor histidine kinase, PorY, to a designated sigma factor. Here, the recombinant expression and purification of PorX homologous proteins from the pathogenic bacterium Porphyromonas gingivalis and the nonpathogenic bacterium Flavobacterium johnsoniae are reported. A bioinformatical characterization of the different domains comprising the PorX protein is also provided, and the crystallization and X-ray analysis of PorX from F. johnsoniae are reported.
The interplay of gendered identities and employees perception of organizational citizenship behavior
Authors: Kaur Navneet , Kang Lakhwinder Singh
Published: September 2022

Purpose

Drawing from the gender schema theory and social role theory, the purpose of this study is to assess the gender-congruent nature of organizational citizenship behaviors (OCBs) through the mediating role of gender role orientation (femininity and masculinity) in the relationship between individuals sex and OCB dimensions. It also explores the moderating effect of gender ideology on the influence of sex on the exhibition of gender-congruent OCBs.

Design/methodology/approach

Data were collected in two waves with a time lag of three weeks from frontline employees and their peers working in the Indian private banking sector. PROCESS macro was used to assess the hypothesized relationships.

Findings

The results indicated that femininity mediated the influence of sex on OCBs directed toward co-workers (OCBI). However, the mediating role of femininity was not confirmed in the association between sex and OCBs targeted toward customers (OCBC). Further, masculinity mediated the influence of sex on OCBs directed toward the organization (OCBO). Gender ideology also moderated the relationship between sex and OCBs, such that traditional women displayed more OCBI as compared to egalitarian women, while egalitarian women displayed more OCBC than traditional women. Additionally, traditional men were found to display more OCBO than egalitarian men.

Originality/value

The paper contributes to the existing literature by suggesting that the performance of OCBs depends upon various gender identities, with each gender identity having its own and significant effect on the performance of OCB.
Are firms with women executives better at surviving a crisis? Evidence from South Korea during the COVID-19 pandemic
Authors: Shin Hyejeong , Park Sorah
Published: September 2022

Purpose

This study aims to examine whether investors react differently to the crisis during the COVID-19 pandemic based on chief executive officer (CEO) gender.

Design/methodology/approach

This study is based on a sample of publicly listed companies in Korea. The study uses the ordinary least squares regression and propensity score matching approach to address the research question. The dependent variable used in the regressions is the cumulative abnormal returns over 30, 60 and 90 days after the first COVID-19 case was confirmed in Korea.

Findings

The results show that cumulative abnormal returns over 30, 60 and 90 days after the first COVID-19 case are less negative for firms led by women CEOs compared to firms led by men CEOs. This is consistent with the prediction that investors favor firms with women CEOs in times of high uncertainty.

Originality/value

This study adds to the growing literature on the stock market during the COVID-19 pandemic. It provides empirical evidence that the effect of the pandemic on stock market performance differs by management characteristics such as CEO gender.
A qualitative analysis of stressors affecting 999 ambulance call handlers' mental health and well-being
Authors: Powell Catherine , Fylan Beth , Lord Kathryn , Bell Fiona , Breen Liz
Published: September 2022

Purpose

The 999 ambulance call handler is critical in responding to emergency patient treatment; however, the call handlers are often a hidden component of the healthcare workforce and an under-researched group. The objective of this study is to understand stress triggers experienced by 999 ambulance call handlers that could lead to burnout and examine personal and organisational mechanisms and strategies which reduced the risk of burnout.

Design/methodology/approach

A single interview case study approach applying qualitative methods was undertaken. Participants were identified through a purposive sample of 999 ambulance call handlers with the Yorkshire Ambulance Service National Health Service Trust (UK). Participants were interviewed via telephone between July 2019 and September 2019.

Findings

In total, 18 staff participated in this study. Societal factors including public incivility and media representation and organisational factors, such as a demanding environment, lack of appreciation and career progression, training issues and protocols were key stressors. Organisational well-being services were helpful for some, but for others lacked accessibility and appropriateness. Positive public feedback and speaking with peers bolstered well-being. 999 ambulance call handlers suggested that sufficient breaks, co-design or feeding back on training and protocols and creating more informal opportunities to discuss ongoing everyday stressors as methods to reduce stress and burnout.

Originality/value

This paper explores a previously under researched area on stressors and potential burnout in 999 call handlers. This paper highlights the need for improved organisational support services and appropriate public and sector peer recognition of the role of ambulance 999 ambulance call handlers.
Technical condition of houses: a framework for the Czech market
Authors: Jandásková Tereza , Hrdlicka Tomas , Cupal Martin , Kleparnik Petr , Komosná Milada , Kervitcer Marek
Published: September 2022

Purpose

This study aims to provide a framework for assessing the technical condition of a house to determine its market value, including the identification of other price-setting factors and their statistical significance. Time on market (TOM) in relation to the technical condition of a house is also addressed.

Design/methodology/approach

The primary database contains 631 houses, and the initial asking price and selling price are examined. All the houses are located in the Brno–venkov district in the Czech Republic. Regression analysis was used to test the influence of price-setting factors. The standard ordinary least squares estimator and the maximum likelihood estimator were used in the frame of generalized linear models.

Findings

Using envelope components of houses separately, such as the façade condition, windows, roof, condition of interior and year of construction, brings better results than using a single factor for the technical condition. TOM was found to be 67 days lower for houses intended for demolition – as compared to new houses – and 18 days lower for houses to refurbishment.

Originality/value

To the best of the authors’ knowledge, this paper is original in the substitution of specific price-setting factors for factors relating to the technical condition of houses as well as in proposing the framework for professionals in the Czech Republic.
Trait resilience and work–family conflict: a two-study test into the role of employees' interpersonal vs. intrapersonal resilient traits
Authors: Nelson Noa , Fuchs Raphaele , Kurtz-Cohen Mayan
Published: September 2022

Purpose

Work–family conflict (WFC) is a chronic source of stress, threatening contemporary organizations. Employees' own characteristics, which have received limited scientific attention, can help mitigate WFC. The current two studies tested, for the first time, the links of higher-order trait resilience models to WFC, while exploring possible mediators and differentiating the contributions of interpersonal vs. intrapersonal resilient traits.

Design/methodology/approach

In study 1, the authors tested a mediation model in which trait negotiation resilience (TNR), which is oriented toward challenges that involve balancing conflicting needs with others, predicted multidimensional (time, strain and behavior based) WFC, through three mediators: emotion regulation (intrapersonal), self-monitoring and work–family balance negotiation (both interpersonally oriented). In study 2, both TNR and the more intrapersonal Connor–Davidson Resilience Scale (CD-RISC) were associated with a global, more parsimonious measurement of WFC. Additionally, TNR's factors were separately correlated with the latter.

Findings

TNR associated with lower multidimensional WFC through emotion regulation, which partly mediated TNR's effect; and through self-monitoring, which suppressed TNR's effect because it related to higher WFC (balance negotiation had no effect). In study 2, CD-RISC, but not TNR, related to lower global WFC. Additionally, two intrapersonal TNR factors tended to relate to lower WFC, while one interpersonal factor related to higher WFC.

Originality/value

The studies demonstrate the role of higher-order trait resilience in WFC, while fine-tuning understanding of the contributions of intrapersonal vs. interpersonal resilience. The findings may be relevant to other organizational challenges, beyond WFC, and inform employee recruitment and training.
Sustainable recovery for people and the planet through spirituality-induced connectedness in the hospitality and tourism industry
Authors: Rezapouraghdam Hamed , Karatepe Osman M. , Enea Constanta
Published: September 2022

Purpose

This paper aims to propose a conceptual model which can be used in tourism and hospitality organizations to nurture human behavior change in favor of people and the planet's well-being.

Design/methodology/approach

A detailed review of the relevant theories and previous studies was conducted in this study.

Findings

Eight propositions have emerged in this research illustrating the mechanisms through which spiritual leadership within organizations can lead to a sustainable recovery of people and the planet during and post-pandemic era.

Practical implications

In line with the United Nation's agenda for sustainable development goals, this paper provides important insights for managers, policymakers, and practitioners on a soft transition toward sustainable business practices as an attempt toward the social, environmental, and economic prosperity for people and the planet.

Originality/value

This research is one of the few studies exploring the contribution of spiritual leadership in tourism and hospitality organizations to the well-being of people and the planet.
Research agenda on turnaround strategies beyond systemic disruptions
Authors: Castelló-Sirvent Fernando , Roger-Monzó Vanessa
Published: September 2022

Purpose

Since the Great Financial Crisis (GFC), the shocks are getting deeper and deeper on the economy, sectors and companies. In these years, turnaround strategies have evolved and contribute to improving the agility and audacity of managers. This article studies the change in the research agenda and in the academic discourse as systemic disruptions become widespread and provides evidence on collaboration networks and publication opportunities.

Design/methodology/approach

This research uses a comparative bibliometric analysis to understand the changes in the academic debate as of 2008. The core collection of Web of Science (WoS) is used and 198 articles on turnaround strategies published in journals indexed in Journal Citation Reports® (JCR) – Social Sciences Citation Index (SSCI) in areas like business, management, economics and finance during 1965–2022.

Findings

This research reveals an important intertemporal evolution between periods, both in the collaborative networks of researchers and in the journals that dominate the impact discourse. In addition, it provides evidence of the change in academic discourse, through the evolution of the topics of interest after the GFC. The results suggest publication opportunities around gaps not yet closed by the academic literature.

Practical implications

This article allows researchers to be guided in identifying gaps that have not yet been closed. In addition, this research has important managerial implications, since it guides and advises journal editors on new emerging issues.

Originality/value

This document offers a global vision on the subject of study and an understanding of the development of the discourse of the academy.
Wild bee communities benefit from temporal complementarity of hedges and flower strips in apple orchards
Authors: von Königslöw Vivien , Fornoff Felix , Klein Alexandra‐Maria
Published: September 2022

Wild bees importantly pollinate both crop and wild plants. Yet, in intensive agricultural landscapes, wild bees are rare due to resource limitations of nectar and pollen. Flower strips and hedges are often used as resource enhancements for wild bees to overcome this shortage, but provide floral resources only during specific time periods. To sustain diverse and stable bee communities, bee‐attractive flowers need to be available during the entire growing season. This may be achieved by combining flower strips and hedges to complement each other and provide continuous floral resources.

Over three subsequent years, we compared the phenology of flower and wild bee communities in perennial flower strips, hedges and improved hedges (complemented with a sown herb layer) in conventional apple orchards in Southern Germany, a pollination‐dependent crop system.

Hedges provided floral resources in the early season while the flower strips took over later in the season.

Bees visited the hedges mostly from March to June, whereas they visited the flower strips from June to August in the first year, and in the second year already from April onwards. Flower strips were visited with an overall higher abundance and species richness than both the hedges and the improved hedges.

Synthesis and application. For enhancing wild bees in intensive apple orchards, hedges and perennial flower strips are complementary in providing flower resources. Yet, flower strips bloom more constantly and during periods of flower scarcity, and thus attract a higher diversity of bees than hedges. Perennial flower strips of different age classes should be preferred over annual strips, at best in a network with some well‐maintained hedges, as perennial flower strips of different age attract different bee communities and thus potentially a higher bee diversity on the landscape level.
Exercise during pregnancy for preventing gestational diabetes mellitus and hypertensive disorders: An umbrella review of randomised controlled trials and an updated meta‐analysis
Authors: Martínez‐Vizcaíno Vicente , Sanabria‐Martínez Gema , Fernández‐Rodríguez Rubén , Cavero‐Redondo Iván , Pascual‐Morena Carlos , Álvarez‐Bueno Celia , Martínez‐Hortelano José Alberto
Published: September 2022

Objective

This study aimed to provide, through an umbrella review, an overview of the effect of single exercise interventions during pregnancy on gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP). Also, to update the current evidence through an updated meta‐analysis.

Design

Umbrella review.

Setting

PubMed, EMBASE, Web of Science, Cochrane database of systematic reviews, Epistemonikos, SPORTDiscus, Clinicaltrials.gov, and PROSPERO register were searched from the database inception until August 2021.

Population

Peer‐reviewed systematic reviews and meta‐analyses of randomised controlled trials (RCTs) and RCTs samples.

Methods

Random‐effects model was used to calculate relative risk with 95% confidence interval in the updated meta‐analysis. The reference category was the groups that received usual prenatal care. AMSTAR 2 and the Cochrane Collaboration tool were used to assess the quality and GRADE approach was used to assess the overall certainly of evidence.

Main outcome measures

GDM and HDP relative risk.

Results

Twenty‐three systematic reviews and meta‐analyses; and 63 RCTs were included. Single exercise interventions reduced the incidence of GDM and HDP in most systematic reviews and meta‐analyses. Moreover, exercise interventions during pregnancy decrease the incidence of developing GDM and GH, particularly when they are supervised, have a low to moderate intensity level, and are initiated during the first trimester of pregnancy.

Conclusion

Based on the findings, obstetric and physical exercise professionals could recommend exercise interventions during pregnancy as an effective strategy to improve maternal outcomes.
A Place Where Women Thrived: UK Social Survey Official Statistics
Authors: Dobbs Joy
Published: September 2022

Women had a strong presence in the workforce of UK Social Survey Official Statistics from its inception. Joy Dobbs was part of a cohort of women recruited in the 1970s and 1980s as government survey statistics expanded. This cohort joined and enhanced an environment and culture that nurtured and developed female talent, including two women who became National Statistician
Necessity of performing a routine chest radiograph following the insertion of tunnelled Hickman catheter under imaging guidance: A single centre experience
Authors: Kato Kosuke , Gan Calvin , Rhodes Alexander
Published: September 2022

Introduction

A chest radiograph has traditionally been performed following the insertion of a tunnelled Hickman catheter to immediately exclude rare but potentially serious complications such as pneumothorax and haemothorax and confirm appropriate positioning of the catheter tip. The value of completing the routine chest radiograph has been questioned when fluoroscopic image may be easily obtained in the angiography suite for the same purpose, and the rate of iatrogenic pneumothorax remains extremely low in the Medical literature. We describe our experience of performing Hickman catheter insertion under ultrasound and fluoroscopic guidance and whether routinely performing the chest radiograph is justifiable.

Methods

A single centre retrospective review was performed of patients who received a tunnelled Hickman catheter and underwent postprocedural chest radiograph in the Interventional Radiology Department during a fifteen‐year period from August 2007 to April 2021. Patient demographics and complications were documented.

Results

Delayed iatrogenic pneumothorax was diagnosed in one asymptomatic patient (0.06%) on a chest radiograph out of 1735 patients, and they required chest tube insertion. Other complications included two cases of right common carotid artery puncture, one case of right internal jugular vein dissection and one case of left internal jugular perforation. Two patients required a repeat procedure within 24 h due to superior migration of the Hickman catheter on chest radiograph.

Conclusion

Given the extremely low rate of iatrogenic pneumothorax, chest radiograph following the insertion of a tunnelled Hickman catheter under ultrasound and fluoroscopic guidance may be an unnecessary investigation unless the patient is symptomatic, or there is sufficient clinical concern.
Male genital organs of the black‐crowned dwarf marmoset (Callibella humilis)
Authors: Vieira Kássia Regina Aguiar , Weber Hiuane Araújo , de Sant’Ana Fabiano José Ferreira , Blume Guilherme Reis , Silva Felipe Ennes , Santana Marcelo Ismar S.
Published: September 2022

This study provides the first morphological description of the male genital organs of black‐crowned dwarf marmoset (Callibella humilis). Internal and external genital organs were similar to other species of non‐human primates. However, some shape and size differences were noted. The penile shaft was laterally flattened and comprised of two corpus cavernosus. These were split by a septum up to the level of the glans and then merged to form a single structure. The glans penis had small, keratinized spicules arising from epidermal or dermal projections. The small, fully ossified and well‐mineralized penile bone, located at the distal end of the penis, consisted of a bone matrix surrounded by sparse osteoblasts and well‐developed internal osteocytes. The penile urethra was lined with columnar pseudostratified epithelium, with areas of simple cuboidal epithelium. The testes were small relative to the body compared to other primate species. The findings of this work may support comparative studies of primate reproductive ecology.
Energizing partnerships in research‐to‐policy projects
Authors: Panter‐Brick Catherine
Published: September 2022

On the ground, how can research initiatives unfold to make meaningful contributions to real‐world practice and real‐time policy? This article draws on a case study evaluating an innovative program to alleviate toxic stress, boost resilience, and promote social inclusion among Syrian refugee and Jordanian nonrefugee youth. I describe the kind of project design and community engagement that animates research on stress biology and lived experiences, connecting people with humanitarian practice and policy. I highlight why and how biocultural work generates fluency in multiple forms of evidence to guide mental health interventions, reflecting on ways to anchor research in shared humanity and shared scientific purpose. I clarify what types of added value, pursued during intersectoral collaborations, help achieve plural, sustained, and inclusive contributions. This article shows how “creative relationality” can energize research‐to‐policy initiatives to bring about transformational change.
Extracellular vesicles from human urine‐derived stem cells merged in hyaluronic acid ameliorate erectile dysfunction in type 2 diabetic rats by glans administration
Authors: Zhuang Jingming , Gao Peng , Chen Haoran , Fang Zujun , Zheng Jie , Zhu Daqian , Hou Jiangang
Published: September 2022

Background

The high prevalence of erectile dysfunction (ED) in patients with type 2 diabetes mellitus (DM2) is a challenging clinical problem. Researches on extracellular vesicles from urine‐derived stem cells (USC‐EVs) have shown that they have significant therapeutic effects in a variety of diseases by injection including ED. Hyaluronic acid (HA) is especially useful for delivering bioactive molecules. This study investigated the effects and related mechanisms of local administration of human USC‐EVs combined with HA (USC‐EVs‐HA) on a rat model of DM2ED.

Methods

UCSs were extracted from human urine samples and identified for preparation of the corresponding USC‐EVs. The effects of high glucose and USC‐EVs on human umbilical vein endothelial cells (HUVECs) were assessed in vitro using a CCK‐8 assay to determine cell proliferation and pick the most appropriate concentration for subsequent experiments. Scratch and tube formation assays were performed to assess the function of HUVECs. Quantitative real‐time polymerase chain reaction (PCR) was used to detect the expression of genes such as B‐cell lymphoma‐2 (Bcl‐2), Bcl‐2‐associated X protein (BAX), and superoxide dismutase‐2 (SOD2). HA, USC‐EVs, and USC‐EVs‐HA were prepared at concentrations and then administered topically to DM2ED rats multiple times. Intracavernous pressure and mean arterial pressure were measured to assess erectile function in rats. Masson, Tunel, Immunohistochemistry, and Western blot analysis were performed to assess the fibrosis and endothelial function in corpus cavernosum, respectively.

Results

Compared with the control group, the proliferation, migration ability, and tube‐forming ability of HUVECs decreased in high glucose environment, while USC‐EVs could optimize the function of HUVECs, reverse the expression of apoptotic genes, and enhance the antioxidant capacity. USC‐EVs‐HA showed improvement in ED compared to the HA and USC‐EVs groups, and the 10‐dose group was better than the 5‐dose group. Histologically, the USC‐EVs‐HA group significantly improved apoptosis, angiogenesis, and smooth muscle regeneration in the corpus cavernosum compared to the HA group.

Conclusions

The topical application of USC‐EVs‐HA in the treatment of DM2ED rats has been proved effective. The potential mechanism might to promote the proliferation of endothelial cells and smooth muscle in the corpus cavernosum, which leads to the remodeling of erectile function. And multiple dosing at intervals may make the effect more pronounced.
Full chimaeric CAR.CIK from patients engrafted after allogeneic haematopoietic cell transplant: Feasibility, anti‐leukaemic potential and alloreactivity across major human leukocyte antigen barriers
Authors: Circosta Paola , Donini Chiara , Gallo Susanna , Giraudo Lidia , Gammaitoni Loretta , Rotolo Ramona , Galvagno Federica , Capellero Sonia , Basiricò Marco , Casucci Monica , Aglietta Massimo , Ferrero Ivana , Fagioli Franca , Cignetti Alessandro , Carnevale‐Schianca Fabrizio , Leuci Valeria , Sangiolo Dario
Published: September 2022

Cytokine‐induced killer lymphocytes (CIK) are a promising alternative to conventional donor lymphocyte infusion (DLI), following allogeneic haematopoietic cell transplantation (HCT), due to their intrinsic anti‐tumour activity and reduced risk of graft‐versus‐host disease (GVHD). We explored the feasibility, anti‐leukaemic activity and alloreactive risk of CIK generated from full‐donor chimaeric (fc) patients and genetically redirected by a chimeric antigen receptor (CAR) (fcCAR.CIK) against the leukaemic target CD44v6. fcCAR.CIK were successfully ex‐vivo expanded from leukaemic patients in complete remission after HCT confirming their intense preclinical anti‐leukaemic activity without enhancing the alloreactivity across human leukocyte antigen (HLA) barriers. Our study provides translational bases to support clinical studies with fcCAR.CIK, a sort of biological bridge between the autologous and allogeneic sources, as alternative DLI following HCT.
Archives and care: Caring archival research practices in geography
Authors: Wideman Trevor J.
Published: September 2022

Archival research has been long recognized as a key method in geography, and such research continues to appeal to scholars excavating historical influences on contemporary places. At the same time, geographical literature on care is growing rapidly. However, while geographers have often implemented care into their archival research and practice, these literatures have remained largely distinct from each other. In this paper, I bring archives and care into closer conversation. Drawing on existing geographical literature on care and on archival methods, work in archival studies, and my own research and ethnographic experiences in archives, I show how the socio‐material practices of geographers in the archives help generate spaces of care, where ethical caring practices exist, and caring relationships flourish. I demonstrate how archival work in geography and beyond includes relationships of care between archivists, researchers, and archival records. I share some examples and strategies that geographers and other researchers can—and do—follow in maintaining, continuing, and repairing archival relationships, even in times of precarity and uncertainty.
Metformin and simvastatin synergistically suppress endothelin 1‐induced hypoxia and angiogenesis in multiple cancer types
Authors: Liu Jie , Wang Huxia , Zhang Miao , Li Yazhao , Wang Ruiqi , Chen He , Wang Bo , Gao Xiaoqian , Song Shaoran , Wang Yaochun , Ren Yu , Li Juan , Liu Peijun
Published: September 2022

Multiple cancers have been reported to be associated with angiogenesis and are sensitive to anti‐angiogenic therapies. Vascular normalization, by restoring proper tumor perfusion and oxygenation, could limit tumor cell invasiveness and improve the effectiveness of anticancer treatments. However, the underlying anticancer mechanisms of antiangiogenic drugs are still unknown. Metformin (MET) and simvastatin (SVA), two metabolic‐related drugs, have been shown to play important roles in modulating the hypoxic tumor microenvironment and angiogenesis. Whether the combination of MET and SVA could exert a more effective antitumor effect than individual treatments has not been examined. The antitumor effect of the synergism of SVA and MET was detected in mouse models, breast cancer patient‐derived organoids, and multiple tumor cell lines compared with untreated, SVA, or MET alone. RNA sequencing revealed that the combination of MET and SVA (but not MET or SVA alone) inhibited the expression of endothelin 1 (ET‐1), an important regulator of angiogenesis and the hypoxia‐related pathway. We demonstrate that the MET and SVA combination showed synergistic effects on inhibiting tumor cell proliferation, promoting apoptosis, alleviating hypoxia, decreasing angiogenesis, and increasing vessel normalization compared with the use of a single agent alone. The MET and SVA combination suppressed ET‐1‐induced hypoxia‐inducible factor 1α expression by increasing prolyl hydroxylase 2 (PHD2) expression. Furthermore, the MET and SVA combination showed a more potent anticancer effect compared with bosentan. Together, our findings suggest the potential application of the MET and SVA combination in antitumor therapy.
Endocrine complications after hematopoietic stem cell transplantation during childhood—Results from a close follow‐up in a cohort of 152 patients
Authors: Figueiredo Ana Abrantes , Cavaco Daniela , Damásio Inês , Maciel Joana , Pinheiro Sara , Donato Sara , Simões‐Pereira Joana
Published: September 2022

Context

Haematopoietic stem cell transplantation (HSCT) is a therapeutic option for numerous haematologic diseases and solid tumours. Increasing indications for HSCT and reduction in associated mortality have been raising the number of paediatric HSCT survivors and their long‐term toxicities.

Objective

To characterize the endocrine disorders developed after HSCT.

Design and Patients

Retrospective analysis of 152 patients submitted to HSCT in paediatric age with at least 24 months of follow‐up at our endocrine late‐effects clinics.

Results

Patients were followed up for 9.9 (interquartile range [IQR]: 12.2) years. The median age at HSCT was 7.5 (IQR: 9) years. At least one endocrine complication was observed in 65.1% of the patients. Primary hypogonadism was detected in 34.2%. Female gender (p < .001), HSCT > 10 years old (p = .01) and chemotherapy before HSCT (p < .001) were identified as risk factors for developing gonadal dysfunction. Growth hormone deficiency (GHD) occurred in 23.0% with a mean stature Z‐score at diagnosis of −1.8 ± 1.4. GHD was associated with cranial (p < .001) and HSCT < 10 years old (p ≤ 0.001). Patients who were exposed to total body irradiation (TBI) were at higher risk for primary hypothyroidism (22.3%) (p = .01), thyroid nodules (17.1%) (p < .001), thyroid carcinoma (5.3%) (p < .001), dyslipidaemia (19.1%) (p < .001) and disturbance of carbohydrate metabolism (19.1%) (p < .001).

Conclusion

At least one endocrine complication was diagnosed in 65.1% of patients, with gonadal dysfunction being the most prevalent. The conditioning regimen with TBI was a risk factor for the development of several endocrine disorders. This study is one of the largest series evaluating the endocrine disorders among survivors of paediatric HSCT and intends to reinforce the importance of routine follow‐up of these patients.
Epigenomic and somatic mutations of pituitary tumors with clinical and pathological correlations in 111 patients
Authors: Guaraldi Federica , Morandi Luca , Zoli Matteo , Mazzatenta Diego , Righi Alberto , Evangelisti Stefania , Ambrosi Francesca , Tonon Caterina , Giannini Caterina , Lloyd Ricardo V. , Asioli Sofia
Published: September 2022

Objective

To profile clinically non‐aggressive and aggressive pituitary adenomas (PAs)/pituitary neuroendocrine tumours (PitNETs) and pituitary carcinomas for somatic mutations and epigenetic alterations of genes involved in cell proliferation/differentiation, microRNAs (miRNA)/long noncoding RNA (LncRNA)‐post‐transcriptional regulators and therapy targets.

Design

Retrospective observational study.

Patients and Measurements

A total of 64 non‐aggressive and 41 aggressive PAs/PitNETs and 6 pituitary carcinomas treated by endoscopic surgery with ≥1‐year follow‐up were included. Somatic mutations of 17 genes and DNA methylation of 22 genes were assessed. Ten normal pituitaries were used as control.

Results

We found at least one mutation in 17 tumours, including 6/64 non‐aggressive, 10/41 aggressive PAs/PitNETs, and 1/6 pituitary carcinoma. AIP (N = 6) was the most frequently mutated gene, followed by NOTCH (4), and TP53 (3). Hypermethylation of PARP15, LINC00599, ZAP70 was more common in aggressive than non‐aggressive PAs/PITNETs (p < .05). Lower levels of methylation of AIP, GNAS and PDCD1 were detected in aggressive PAs/PITNETs than non‐aggressive ones (p < .05). For X‐linked genes, males presented higher level of methylation of FLNA, UXT and MAGE family (MAGEA11, MAGEA1, MAGEC2) genes in aggressive vs. non‐aggressive PAs/PITNETs (p < .05).

In pituitary carcinomas, methylation of autosomal genes PARP15, LINC00599, MIR193 and ZAP70 was higher than in PAs/PITNETs, while X‐linked genes methylation level was lower.

Conclusions

Somatic mutations and methylation levels of genes involved in cell proliferation/differentiation, miRNA/LncRNA‐post‐transcriptional regulators and targets of antineoplastic therapies are different in non‐aggressive and in aggressive PAs/PitNETs. Methylation profile also varies according to gender. Combined genetic‐epigenetic analysis, in association with clinico‐radiological‐pathological data, may be of help in predicting PA/PitNET behaviour.
Disseminated rhinosporidiosis masquerading as soft tissue round cell tumour diagnosed by fine needle aspiration cytology
Authors: Balasubramaniam Vidhya Vikashini , Ramamoorthi Subhashini , Nadeem Naadia , Sekar Mithraa Devi , Gochhait Debasis , Siddaraju Neelaiah
Published: September 2022

Rhinosporidium seeberi belongs to the eukaryotic class Mesomycetozoea and causes chronic granulomatous lesions known as rhinosporidiosis. Rhinosporidiosis frequently involves the nasal cavity and nasopharynx through transepithelial invasion. Atypical presentations of this disease at other body sites have been reported, including the subcutis, visceral organs, bones, and genitals. Only a few cases of cutaneous and subcutaneous involvement have been reported to date. This chronic granulomatous condition is known for its recurrence following autoinoculation unless the correct diagnosis and appropriate treatment are given. We describe a case of an immunocompetent adult who had undergone fine needle aspiration cytology (FNAC) of mass‐like swellings in the right thigh and right calf at another healthcare centre and had been diagnosed with a small round blue cell tumour. FNAC at our centre confirmed a rare case of rhinosporidiosis that was clinically mimicking a soft tissue neoplasm of the lower extremity, and the erroneous interpretation of the prior cytology studies had resulted in misinterpretation of the individually dispersed pathogenic organisms as individual malignant cells. FNAC of rhinosporidiosis can lead to early diagnosis and prompt treatment of this pathogen when it presents at unanticipated body sites.
The Virus, the Dollar, and the Global Order: The COVID‐19 Crisis in Comparative Perspective
Authors: Hung Ho‐fung
Published: September 2022

In 2003, the SARS pandemic led to a framework of global public health governance which was characterized by cooperation between the USA and China, and China's increasing influence in the World Health Organization. In the wake of the global financial crisis of 2008, major economies of the world, above all the USA, established the standard of aggressive fiscal and monetary expansion to mitigate any major crisis of the global economy. The effectiveness of such expansions in bringing global economic recovery without fuelling out‐of‐control inflation hinged on the deepening of US–China economic integration. These global health and economic governance frameworks, which emerged from two previous crises, conditioned the global response to the COVID‐19 pandemic in 2020. Ironically, the COVID‐19 crisis and the global responses to it undermined the legitimacy of the global public health governing institutions and further aggravated US–China rivalry, which had started before the pandemic. On the other hand, the crisis sustained economic integration between the two countries, despite the US–China trade war that began on the eve of the pandemic. This contradictory geopolitical and geo‐economic fallout of the COVID‐19 crisis will bring more uncertainty and instability to the global order in the wake of the pandemic.
Gene activation of metazoan Fox transcription factors at the onset of metamorphosis in the marine demosponge Amphimedon queenslandica
Authors: Yuan Huifang , Hatleberg William L. , Degnan Bernard M. , Degnan Sandie M.
Published: September 2022

Transcription factors encoded by the Forkhead (Fox) gene family have diverse, sometimes conserved, regulatory roles in eumetazoan development, immunity, and physiology. Although this gene family includes members that predate the origin of the animal kingdom, the majority of metazoan Fox genes evolved after the divergence of animals and choanoflagellates. Here, we characterize the composition, structure, and expression of Fox genes in the marine demosponge Amphimedon queenslandica to better understand the origin and evolution of this family. The Fox gene repertoire in A. queenslandica appears to be similar to the ancestral metazoan Fox gene family. All 17 A. queenslandica Fox genes are differentially expressed during development and in adult cell types. Remarkably, eight of these, all of which appear to be metazoan‐specific, are induced within just 1 h of larval settlement and commencement of metamorphosis. Gene co‐expression analyses suggest that these eight Fox genes regulate developmental and physiological processes similar to their roles in other animals. These findings are consistent with Fox genes playing deeply ancestral roles in animal development and physiology, including in response to changes in the external environment.
Survival of individuals with cerebral palsy in Victoria, Australia: A longitudinal cohort study spanning four decades
Authors: Hinwood Gina L. , Loftus Hayley , Shepherd Daisy A. , Guzys Angela , Reddihough Dinah S. , Reid Susan M.
Published: September 2022

Aim

To provide an updated description of the rates, trends, and predictors of mortality of individuals with cerebral palsy (CP), born in the Australian state of Victoria between 1970 and 2012.

Method

Data were extracted for 4807 individuals (2091 females; 2716 males). The probability of survival to 30th June 2017 was calculated using the Kaplan–Meier method. Mortality rates were calculated per 1000 person‐years using age strata and compared with population mortality rates to produce mortality ratios. Cox proportional hazards regression was used to calculate hazard ratios for selected demographic and clinical characteristics and to estimate the effect of birth epoch on 15‐year survival.

Results

There were 666 recorded deaths. Compared to the general population, mortality was higher for all persons with CP and highest for children aged 1 to 15 years (45–62 times). We observed 35% improvement in the probability of survival to 15 years for births in the 2000s relative to the 1970s (hazard ratio 0.65, 95% confidence interval [CI] 0.49, 0.86), but only 4% improvement for the subgroup with complex CP (hazard ratio 0.96, 95% CI 0.69, 1.33).

Interpretation

The observed improvements in survival for those born in the 2000s is likely related predominantly to a proportional reduction in complex CP within the cohort.

What this paper adds

Length of survival improved for Australians with cerebral palsy (CP) born this millennium.

Improved survival was mainly because of a proportional reduction in complex CP.

A small improvement in length of survival was seen for children with complex CP.