bluuebunny/crossref_metadata_2025 huggingface dataset:
Gastrin and somatostatin enteroendocrine cells in the small intestines of ostrich (Struthio camelus var. domesticus) during pre ‐and post‐hatching period
Authors: Dūrītis Ilmārs , Hussar Piret , Mugurēvičs Arnis
Published: February 2021

Studies on localization and distribution of enteroendocrine cells (EECs) are important for better understanding of their role in the ontogenetic development of intestines. Information about the distribution of the most important endocrine cells in the digestive tract of the ostrich is very limited; therefore, the aim of the present study was to identify gastrin and somatostatin EECs in the small intestine of the ostrich (Struthio camelus var. domesticus) chicks at different ages. Six embryos along with 42 ostriches of both sexes from hatching up to 60 days post‐hatching, including six embryos, were obtained from an ostrich farm in Latvia. Duodenum, jejunum and ileum were investigated using routine histology and immunohistochemistry methods. Gastrin and somatostatin EECs were examined in 10 microscopic fields of the intestinal mucosa in each tissue sample. The cells were detected in all age groups as well as the embryos. The number of both types of EEC in the mucosa of the ileum was significantly lower (p < .01–.05) than in the duodenum. The present study suggested that the EEC may have a role in the development of the mucosa of the intestinal tract of ostriches with possible involvement in the development of the digestive functions.
Coming into fashion: Expanding the entrepreneurial ecosystem concept to the creative industries through a Toronto case study
Authors: Brydges Taylor , Pugh Rhiannon
Published: February 2021

This paper considers the entrepreneurial ecosystem concept, which in recent years has gained interest from a variety of perspectives including entrepreneurship, management, and economic geography. Specifically, the paper identifies a gap in the literature regarding the concept's sectoral or industrial focus. Prior applications to real‐world case studies have focused on a fairly narrow range of industries and places. In this paper, we apply the concept to a case study of one creative and cultural industry, the fashion industry, to help us understand not only the performance and function of entrepreneurs and small businesses in this industries, but also potential policy supports. We map the institutions and spaces in Toronto's entrepreneurial ecosystem, drawing on extensive qualitative research to consider the dynamics and interactions therein. In parallel, we advance the concept theoretically, questioning its tenability and applicability in a wider range of economic systems by adding the perspective of cultural and creative industries.
Understanding local government responses to alcohol‐related harm
Authors: Guizzo Miranda , Ward Bernadette , Wilkinson Claire , Vally Hassan , Kuntsche Sandra
Published: February 2021

Introduction

Local governments (LG) have a key role in reducing alcohol‐related harm, yet, Australian research investigating this is limited. This study aimed to explore Australian LGs' role in alcohol policy by investigating how LGs respond to alcohol‐related harm and what influences their responses.

Methods

A collective case study approach guided two‐stage purposive sampling. Victorian metropolitan and regional LGs were invited to participate based on alcohol‐related harm profiles. Officers within LGs with alcohol policy knowledge participated in semi‐structured interviews. Transcripts were analysed deductively using a pre‐existing alcohol policy framework and inductively using thematic analysis.

Results

Nine officers from eight LGs participated. LG responses to alcohol‐related harm predominately included bans on alcohol in public spaces, licensed premises planning and alcohol‐free youth events. Half implemented liquor forums/accords and most implemented education programs in sporting clubs, schools or workplaces. In some LGs, the reduction of alcohol‐related harm was not considered a priority. Key influences on alcohol initiatives were legislation, the composition of licensed venues, extent of alcohol‐related harms, resources and priorities, and stakeholder feedback.

Discussion and Conclusions

While particular policies were widespread, participating LGs varied greatly in activity in, and responses to, reducing alcohol‐related harm. LGs reported varied influences on their responses. LGs recognised the long‐term health harms of alcohol in their health planning documents, however, most prioritised interventions targeting short‐term amenity and safety harms. Changes to Victorian planning and liquor licensing legislation to give additional powers to LGs and providing pre‐developed alcohol programs with dedicated funding should be considered.
The long and winding road to target protein misfolding in cardiovascular diseases
Authors: Diteepeng Thamonwan , del Monte Federica , Luciani Marco
Published: February 2021

Background

In the last decades, cardiovascular diseases (CVD) have remained the first leading cause of mortality and morbidity in the world. Although several therapeutic approaches have been introduced in the past, the development of novel treatments remains an important research goal, which is hampered by the lack of understanding of key mechanisms and targets. Emerging evidences in recent years indicate the involvement of misfolded proteins aggregation and the derailment of protein quality control in the pathogenesis of cardiovascular diseases. Several potential interventions targeting protein quality control have been translated from the bench to the bedside to effectively employ the misfolded proteins as promising therapeutic targets for cardiac diseases, but with trivial results.

Design

In this review, we describe the recent progresses in preclinical and clinical studies of protein misfolding and compromised protein quality control by selecting and reporting studies focusing on cardiovascular diseases including cardiomyopathies, cardiac amyloidosis, atherosclerosis, atrial fibrillation and thrombosis.

Results

In preclinical models, modulators of several molecular targets (eg heat shock proteins, unfolded protein response, ubiquitin protein system, autophagy and histone deacetylases) have been tested in various conditions with promising results although lacking an adequate transition towards clinical setting.

Conclusions

At present, no therapeutic strategies have been reported to attenuate proteotoxicity in patients with CVD due to a lack of specific biomarkers for pinpointing upstream events in protein folding defects at a subclinical stage of the diseases requiring an intensive collaboration between basic scientists and clinicians.
High preharvest donor Foxp3 mRNA level predicts late relapse of acute lymphoblastic leukaemia after haematopoietic stem cell transplantation
Authors: Jacobsen Niels , Frisch Tina , Keiding Niels , Heilmann Carsten , Sengeløv Henrik , Madsen Hans O. , Marquart Hanne , Dickmeiss Ebbe , Andersen Mette K. , Christiansen Claus B. , Ryder Lars P.
Published: February 2021

Objectives

The curative effect of allogeneic haematopoietic stem cell transplantation (HSCT) for acute leukaemia is due in part to the donor T cell–mediated graft‐versus‐leukaemia immune reaction (GvL). Several studies have suggested that donor CD25+CD4+Foxp3+regulator T cells (Tregs) may decrease graft‐versus‐host disease (GvHD) without abrogating GVL. This notion may need modification in acute lymphoblastic leukaemia (ALL).

Methods

Foxp3 mRNA level was measured by qPCR in preharvest donor blood CD4+ T cells. The study comprised 45 patients with ALL in 1st or 2nd CR who received myeloablative HSCT using T‐replete bone marrow grafts.

Results

Relapse occurred in 17 patients median 363 days after HSCT. The relapse risk was estimated by Cox univariate and multivariate proportional hazard regression. The proportionality assumption was met by analysing the preharvest donor Foxp3 mRNA level as a time‐dependent covariate. Early relapse was not modified by the Foxp3 mRNA level. However, a higher Foxp3 mRNA level was associated with a significantly increased relapse risk after day 363 after transplantation, compatible with inhibition of GvL. In contrast, a higher preharvest donor CD4+ T‐cell concentration was associated with reduced relapse risk.

Conclusion

A higher preharvest donor Foxp3 mRNA level may be predictive of late ALL relapse after HSCT.
Targeted therapy response in early versus late recurrence of renal cell carcinoma after surgical treatment: A propensity score‐matched study using the Korean Renal Cancer Study Group database
Authors: Lee Chan Ho , Chung Jinsoo , Kwak Cheol , Jeong Chang Wook , Seo Seong Il , Kang Minyong , Hong Sung‐Hoo , Song Cheryn , Park Jae Young , Hwang Eu Chang , Lee Hakmin , Ku Ja Yoon , Seo Won Ik , Choi Seock Hwan , Ha Hong Koo ,   the Korean Renal Cancer Study Group
Published: February 2021

Objectives

To investigate the clinicopathological features and outcomes of targeted therapy in patients with recurrence of renal cell carcinoma in <5 years or ≥5 years after the surgical treatment for renal cell carcinoma.

Methods

Patients with metastatic renal cell carcinoma treated with targeted therapy in a multicenter database were retrospectively characterized according to time from surgery to recurrence. Early recurrence was defined as recurrence within 5 years after surgery, and late recurrence was defined as occurring ≥5 years after surgery. The propensity scores for recurrence status were calculated, and patients with late recurrence were matched to patients with early recurrence at a 1:3 ratio. The oncological outcomes of targeted therapy in both groups were compared.

Results

Among 716 patients, 512 (71.5%) experienced early recurrence and 204 (28.5%) experienced late recurrence. The patients with late recurrence presented with younger age at surgery, lower tumor stages and Fuhrman grade, and fewer sarcomatoid features and lymphovascular invasion (all P < 0.005). All differences in clinicopathological characteristics before targeted therapy disappeared after matching. Patients with late recurrence had significantly longer median overall survival (56 months vs 36 months; P < 0.0001) and median first‐line progression‐free survival (12 months vs 8 months; P = 0.031). The early recurrence status was a significantly worse predictor for overall survival and first‐line progression‐free survival (hazard ratio 1.30, P = 0.007; and hazard ratio 1.76, P < 0.001, respectively).

Conclusions

Late recurrence might have prognostic value in terms of oncological outcomes in metastatic renal cell carcinoma treated with targeted therapy.
Clinical utility of head computed tomography scan during systemic therapy for metastatic renal cell carcinoma
Authors: Naito Sei , Narisawa Takafumi , Kato Tomoyuki , Ichiyanagi Osamu , Kurokawa Masayuki , Yagi Mayu , Kanno Hidenori , Kurota Yuta , Yamagishi Atsushi , Sakurai Toshihiko , Nishida Hayato , Yamanobe Takuya , Tsuchiya Norihiko
Published: February 2021

Objectives

The utility of brain metastasis screening in asymptomatic metastatic renal cell carcinoma is controversial. Our study evaluated the utility of routine head computed tomography during systemic therapy.

Methods

We retrospectively investigated 152 metastatic renal cell carcinoma patients who did not initially have brain metastasis at Yamagata University Hospital from January 2008 to July 2019. Patients who routinely received head computed tomography scan together with routine contrast‐enhanced chest/abdominal/pelvic computed tomography scan every 2–4 months during systemic therapy (“Routine head computed tomography” group, n = 95) and patients without routine head computed tomography (“No routine head computed tomography” group, n = 57) were compared.

Results

Brain metastasis occurred in 16 patients in the “Routine head computed tomography” group and six patients in the “No routine head computed tomography” group. There was no statistical difference in overall survival after metastatic renal cell carcinoma diagnosis between groups (53.4 vs 37.3 months, respectively, P = 0.357) and neurological symptom‐free survival after metastatic renal cell carcinoma diagnosis (53.4 vs 36.6 months, P = 0.336). Although there was no statistical difference on incidence of unrecovered neurological symptom (25.0% vs 50.0%, P = 0.334), fewer patients in the “Routine head computed tomography” group required craniotomy (0% vs 66.7%, P = 0.002). In the “No routine head computed tomography” group, the neurological symptom resolved for all patients without craniotomy.

Conclusions

Routine head computed tomography during systemic therapy for metastatic renal cell carcinoma is not significantly associated with improved brain metastasis prognosis. However, routine head computed tomography enables brain metastasis diagnosis in the asymptomatic phase, which can avoid craniotomy.
Quenching‐circumvented ergodicity in relaxor Na1/2Bi1/2TiO3‐BaTiO3‐K0.5Na0.5NbO3
Authors: Wei Qiumei , Riaz Adeel , Zhukov Sergey , Hofmann Kathrin , Zhu Mankang , Hou Yudong , Rödel Jürgen , Kodumudi Venkataraman Lalitha
Published: February 2021

Quenching alkaline bismuth titanates from sintering temperatures results in increased lattice distortion and consequently higher depolarization temperature. This work investigates the influence of quenching on the ergodicity of relaxor Na1/2Bi1/2TiO3‐BaTiO3‐K0.5Na0.5NbO3. A distinct departure from ergodicity is evidenced from the increase in remanent polarization and the absence of frequency dispersion in the permittivity response of poled samples. Further, the samples exhibit enhanced negative strain upon application of electric field, indicating proclivity towards correlated polar nanoregions, corroborated by the enhanced tetragonal distortion. As a result, ergodic relaxor Na1/2Bi1/2TiO3‐6BaTiO3‐3K0.5Na0.5NbO3 exhibits a depolarization temperature of 85°C with a 60% increase in remanent polarization and approximately a threefold increase in remanent strain upon quenching. Quenching‐induced changes in the local environment of Na+ and Bi3+ cations hinder the development of ergodicity promoted by the A‐site disorder. These results provide new insight into tailoring ergodicity of relaxor ferroelectrics.
Long‐term outcomes of index cryoballoon ablation or point‐by‐point radiofrequency ablation in patients with atrial fibrillation and systolic heart failure
Authors: Prabhu S. , Ahluwalia N. , Tyebally S. M. , Dennis A. S. C. , Malomo S. O. , Abiodun A. T. , Tyrlis A. , Dhillon G. , Segan L. , Graham A. , Honarbakhsh S. , Sawhney V. , Sporton S. , Lowe M. , Finlay M. , Earley M. J. , Lambiase P. , Schilling R. J. , Hunter R. J.
Published: February 2021

Catheter ablation is an established effective approach for the treatment of atrial fibrillation (AF) in patients with heart failure, however, the role of cryoablation in this setting is unclear. Procedural success and left ventricular systolic dysfunction (LVEF) improvement in patients with LVEF ≤ 45% undergoing index catheter ablation with cryoablation were evaluated. Freedom from AF recurrence was seen in 43% rising to 59% following repeat procedure. There were significant improvements in LVEF and functional status at long‐term follow‐up. Results were comparable to a contemporaneous cohort of heart failure patients undergoing index ablation with radiofrequency ablation. Cryoablation is an effective first‐line AF ablation approach in the setting of heart failure.
Gene expression profiles of oral soft tissue‐derived fibroblast from healing wounds: correlation with clinical outcome, autophagy activation and fibrotic markers expression
Authors: Rojas Mariana Andrea , Ceccarelli Simona , Gerini Giulia , Vescarelli Enrica , Marini Lorenzo , Marchese Cinzia , Pilloni Andrea
Published: February 2021

Aim

Our aim was to evaluate gene expression profiling of fibroblasts from human alveolar mucosa (M), buccal attached gingiva (G) and palatal (P) tissues during early wound healing, correlating it with clinical response.

Materials and Methods

M, G and P biopsies were harvested from six patients at baseline and 24 hr after surgery. Clinical response was evaluated through Early wound Healing Score (EHS). Fibrotic markers expression and autophagy were assessed on fibroblasts isolated from those tissues by Western blot and qRT‐PCR. Fibroblasts from two patients were subjected to RT2 profiler array, followed by network analysis of the differentially expressed genes. The expression of key genes was validated with qRT‐PCR on all patients.

Results

At 24 hr after surgery, EHS was higher in P and G than in M. In line with our clinical results, no autophagy and myofibroblast differentiation were observed in G and P. We observed significant variations in mRNA expression of key genes: RAC1, SERPINE1 and TIMP1, involved in scar formation; CDH1, ITGA4 and ITGB5, contributing to myofibroblast differentiation; and IL6 and CXCL1, involved in inflammation.

Conclusions

We identified some genes involved in periodontal soft tissue clinical outcome, providing novel insights into the molecular mechanisms of oral repair (ClinicalTrial.gov‐NCT04202822).
Diagnostic features of SARS‐COVID‐2‐positive patients: A rapid review and meta‐analysis
Authors: Anderson Gloria , Casasanta Daniela , Cocchieri Antonello , D'Agostino Fabio , Zega Maurizio , Damiani Gianfranco , Rega Maria Luisa
Published: February 2021

Aims

To identify the main diagnostic features of SARS‐CoV‐2‐positive patients at the time of hospitalisation and their prevalence.

Background

Since the COVID‐19 outbreak in China in December of 2019, several studies attempted to identify the epidemiological, viral and clinical characteristics of SARS‐CoV‐2. Given the rapid widespread transmission of the COVID‐19 disease worldwide, a more comprehensive and up‐to‐date understanding of its features is needed to better inform nurses, clinicians and public health policy makers.

Methods

A rapid review and meta‐analysis were carried out to identify the main diagnostic features of SARS‐CoV‐2‐positive patients at the time of hospitalisation. All case series, cross‐sectional, case–control and cohort studies published from 01/01/2020 till 30/06/2020 in English and Chinese that stated all or at least two of the outcomes of interest (clinical features, laboratory and radiological findings) were included. We performed a random‐effects model meta‐analysis to calculate pooled prevalence and 95% confidence intervals. Conduction of the review adheres to the PRISMA checklist.

Results

21 studies involving 8837 patients were included in the quantitative synthesis. Fever, cough and fatigue were the most common clinical features, while the most relevant laboratory abnormalities at the time of hospitalisation were lymphopenia, elevated C‐reactive protein and lactate dehydrogenase. CT images showed a bilateral lung involvement, with ground glass infiltrates and patchy shadows on most patients.

Conclusion

This review provides an up‐to‐date synthesis of main diagnostic features of SARS‐CoV‐2‐positive patients at the time of hospitalisation.

Relevance to Clinical Practice

Our findings could provide guidance for nurses and clinicians to early identification of positive patients at the time of the hospitalisation through a complete definition of main clinical features, laboratory and CT findings.
Heterogeneous genetic basis of age at maturity in salmonid fishes
Authors: Waters Charles D. , Clemento Anthony , Aykanat Tutku , Garza John Carlos , Naish Kerry A. , Narum Shawn , Primmer Craig R.
Published: February 2021

Understanding the genetic basis of repeated evolution of the same phenotype across taxa is a fundamental aim in evolutionary biology and has applications in conservation and management. However, the extent to which interspecific life‐history trait polymorphisms share evolutionary pathways remains underexplored. Here, we address this gap by studying the genetic basis of a key life‐history trait, age at maturity, in four species of Pacific salmonids (genus Oncorhynchus) that exhibit intra‐ and interspecific variation in this trait—Chinook Salmon, Coho Salmon, Sockeye Salmon, and Steelhead Trout. We tested for associations in all four species between age at maturity and two genome regions, six6 and vgll3, that are strongly associated with the same trait in Atlantic Salmon (Salmo salar). We also conducted a genome‐wide association analysis in Steelhead to assess whether additional regions were associated with this trait. We found the genetic basis of age at maturity to be heterogeneous across salmonid species. Significant associations between six6 and age at maturity were observed in two of the four species, Sockeye and Steelhead, with the association in Steelhead being particularly strong in both sexes (p = 4.46 × 10−9 after adjusting for genomic inflation). However, no significant associations were detected between age at maturity and the vgll3 genome region in any of the species, despite its strong association with the same trait in Atlantic Salmon. We discuss possible explanations for the heterogeneous nature of the genetic architecture of this key life‐history trait, as well as the implications of our findings for conservation and management.
A case of idiopathic extracranial carotid artery pseudoaneurysm with a rare clinical course and pathological features
Authors: Nomura Shunsuke , Yoneyama Taku , Kawashima Akitsugu , Yamaguchi Koji , Ishikawa Tatsuya , Okada Yoshikazu , Shibata Noriyuki , Kawamata Takakazu
Published: February 2021

Extracranial carotid artery aneurysms (ECAAs) are rare, with the etiology mainly classified as degeneration or dissection. Pseudoaneurysms in the region are even rarer and are seen following trauma, iatrogenic injury, or infection. We report a case of extracranial carotid artery pseudoaneurysm (pseudo‐ECAA) with a rare clinical course and pathological features. A 58‐year‐old man presented with swelling and purpura on the left side of his neck after sneezing. Radiological examinations suggested a ruptured left common carotid artery aneurysm. The operative findings were consistent with a pseudoaneurysm. Pathological examination revealed disarrangement and degeneration of smooth muscle fibers in the media, in addition to scattered foci of mucoid accumulation and irregular‐shaped cavitation in the medial extracellular matrix, raising the possibility of an intrinsic dysfunction of the vascular wall in the pathological process of pseudoaneurysm formation.
Pathogenesis of obesity and cardiometabolic diseases: From the legacy of Ancel Keys to current concepts
Authors: Dulloo Abdul G. , Montani Jean‐Pierre
Published: February 2021

Several areas of research into the prevention and treatment of obesity today can be traced to one or more of the scientific works pioneered by Ancel Keys between the 1930s to 1970s in fields that cut across the physiology of extremes and public health nutrition. These range from his classical studies into how body and mind respond to chronic exposure to hypoxia in“The Physiology of Life at High Altitudes”or to simulated famine under controlled laboratory conditions in“The Biology of Human Starvation”, the impact of diet and lifestyle on cardiovascular morbidity and mortality in“The Seven Countries Study,”to the“Indices of Relative Weight and Obesity”in which he identified what has since been the most widely utilized diagnostic tool to monitor obesity across populations worldwide and which he coined as the body mass index. The contribution of Ancel Keys to medical sciences through his observations, analytical approaches, and research output of his classic studies, and how these have (and continue) to impact on a plethora of current concepts in obesity research today, are embodied in the eight review articles that constitute this supplement reporting the proceedings of the 10th Fribourg Obesity Research Conference. The aim of this introductory paper is to put into perspective the legacy of Ancel Keys to current concepts that are encapsulated in these review articles that cover research areas that include (i) the diagnosis of obesity for health risks; (ii) the role of dietary fat types in the pathogenesis of obesity and cardiometabolic diseases; (iii) the rationale, efficacy and safety of low carbohydrate ketogenic diets, or the therapeutic potential of hypoxic conditioning, in weight management programs; (iv) the psychological and physiological basis of the “famine reaction” that counters therapeutic dieting and facilitates weight regain; and (v) the potential impact of weight cycling and yoyo dieting on risks for later obesity and cardiometabolic diseases.
Psychometric comparisons of measures of eHealth literacy using a sample of Korean older adults
Authors: Kim Hyunjung , Yang Eunjin , Ryu Hyunju , Kim Hee Jung , Jang Sun Joo , Chang Sun Ju
Published: February 2021

Aims

This study aimed to compare the psychometric properties of two measures of eHealth literacy, namely, the Korean versions of the Digital Health Literacy Instrument (K‐DHLI) and eHealth Literacy Scale (K‐eHEALS), among older adults in South Korea.

Background

Given the usefulness of eHealth information, measures of eHealth literacy have been developed. It is necessary to examine the validity of such tools among older adults who are likely to experience difficulties in using eHealth resources.

Methods

A validation study was conducted using the secondary data of 180 older adults in South Korea. Two weeks after they had responded to the K‐DHLI and K‐eHEALS, 89 of them completed the assessments a second time so that the assessments’ test–retest reliability could be examined. Using the collected data, their reliability (i.e. internal consistency, test–retest reliability) and validity (i.e. construct validity and criterion validity) were examined.

Results

Both tools demonstrated satisfactory internal consistency (α ≥ 0.90, item‐total correlation coefficients = .39–.76) as well as good test–retest reliability with intraclass correlation coefficients .77 and .84, respectively. The 21 items of the K‐DHLI loaded onto five factors, which accounted for 71% of the variance. The 10 items of the K‐eHEALS loaded onto a single factor, which explained 58% of the total variance. The scores of both tools were strongly correlated (r = .63) and positively related to attitudes towards internet health information and subjective health status (r = .23–.50).

Conclusions

The findings suggest that the K‐DHLI and K‐eHEALS are reliable and valid tools that can be used to assess the utilisation of eHealth resources by older adults.

Implications for Practice

The findings can help healthcare providers choose a suitable measure of eHealth literacy when working with older adults.
The corporatization of healthcare organizations internationally: A scoping review of processes, impacts, and mediators
Authors: Turner Simon , Wright John S. F.
Published: February 2021

Corporatization, the conversion of state‐owned enterprises into semi‐autonomous, legally independent entities, has gained in popularity internationally since the 1980s. This review suggests that usage of the term has become entangled with other definitions of corporatization, and other organizational reforms associated with new public management, and appears consequently to have lost its distinctiveness in many contemporary studies of corporatization. Through a scoping review of literature on corporatization of healthcare organizations internationally, we develop a typology of four perspectives on corporatization (as managerialism of medical work, as institutional level reform to encourage market‐like behavior, as corporate governance implications of legal independence, and as private sector colonization) and analyze the specific processes, impacts, and mediators associated with each approach. This typology can aid conceptual clarity in future research on corporatization and orient practitioners to particular management and policy questions within the complex field of reform signified by this term.
Early humoral defence: Contributing to confining COVID‐19 to conducting airways?
Authors: Persson Carl
Published: February 2021

Early airway responses to severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection are of interest since they could decide whether coronavirus disease‐19 (COVID‐19) will proceed to life‐threatening pulmonary disease stages. Here I discuss endothelial‐epithelial co‐operative in vivo responses producing first‐line, humoral innate defence opportunities in human airways. The pseudostratified epithelium of human nasal and tracheobronchial airways are prime sites of exposure and infection by SARS‐CoV‐2. Just beneath the epithelium runs a profuse systemic microcirculation. Its post‐capillary venules respond conspicuously to mucosal challenges with autacoids, allergens and microbes, and to mere loss of epithelium. By active venular endothelial gap formation, followed by transient yielding of epithelial junctions, non‐sieved plasma macromolecules move from the microcirculation to the mucosal surface. Hence, plasma‐derived protein cascade systems and antimicrobial peptides would have opportunity to operate jointly on an unperturbed mucosal lining. Similarly, a plasma‐derived, dynamic gel protects sites of epithelial sloughing‐regeneration. Precision for this indiscriminate humoral molecular response lies in restricted location and well‐regulated duration of plasma exudation. Importantly, the endothelial responsiveness of the airway microcirculation differs distinctly from the relatively non‐responsive, low‐pressure pulmonary microcirculation that non‐specifically, almost irreversibly, leaks plasma in life‐threatening COVID‐19. Observations in humans of infections with rhinovirus, coronavirus 229E, and influenza A and B support a general but individually variable early occurrence of plasma exudation in human infected nasal and tracheobronchial airways. Investigations are warranted to elucidate roles of host‐ and drug‐induced airway plasma exudation in restriction of viral infection and, specifically, whether it contributes to variable disease responses following exposure to SARS‐CoV‐2.
Identification of a new HLA‐B*44 allele, HLA‐B*44:02:68, by next generation sequencing
Authors: Troiano Maria , Locatelli Franco , Giustiniani Paola , Bianculli Antonio G. , Andreani Marco
Published: February 2021

HLA‐B*44:02:68 differs from B*44:02:01:01 by one synonmous nucleotide substitution in codon‐10 GGG‐ > GGA.
Perturbation of nuclear–cytosolic shuttling of Rx1 compromises extreme resistance and translational arrest of potato virus X transcripts
Authors: Richard Manon M. S. , Knip Marijn , Schachtschabel Joëlle , Beijaert Machiel S. , Takken Frank L. W.
Published: February 2021

Many plant intracellular immune receptors mount a hypersensitive response (HR) upon pathogen perception. The concomitant localized cell death is proposed to trap pathogens, such as viruses, inside infected cells, thereby preventing their spread. Notably, extreme resistance (ER) conferred by the potato immune receptor Rx1 to potato virus X (PVX) does not involve the death of infected cells. It is unknown what defines ER and how it differs from HR‐based resistance. Interestingly, Rx1 can trigger an HR, but only upon artificial (over)expression of PVX or its avirulence coat protein (CP). Rx1 has a nucleocytoplasmic distribution and both pools are required for HR upon transient expression of a PVX‐GFP amplicon. It is unknown whether mislocalized Rx1 variants can induce ER upon natural PVX infection. Here, we generated transgenic Nicotiana benthamiana producing nuclear‐ or cytosol‐restricted Rx1 variants. We found that these variants can still mount an HR. However, nuclear‐ or cytosol‐restricted Rx1 variants can no longer trigger ER or restricts viral infection. Interestingly, unlike the mislocalized Rx1 variants, wild‐type Rx1 was found to compromise CP protein accumulation. We show that the lack of CP accumulation does not result from its degradation but is likely to be linked with translational arrest of its mRNA. Together, our findings suggest that translational arrest of viral genes is a major component of ER and, unlike the HR, is required for resistance to PVX.
Specialisation within global value chains: Transport infrastructure matter upstream
Authors: Lanz Rainer , Piermartini Roberta
Published: February 2021

This paper studies the factors of comparative advantage within global value chains relying on a framework where comparative advantage is measured through the interaction of country and industry characteristics. We find that good institutions give a comparative advantage in the later stages of the production process, whereas good transport infrastructure gives an advantage in the early stages of production. We explain these results by pointing at whether trade costs are additive or multiplicative.
Introduction of nucleic acid amplification technology for blood screening in Hungary
Authors: Siposné Sohajda Réka , Kokavecz László , Baróti‐Tóth Klára , Nagy Sándor , Paholcsek Melinda , Stágel Anikó
Published: February 2021

Background & Aims

With this study, we intended to report our experiences about introducing nucleic acid testing for blood donation screening for human immunodeficiency virus, hepatitis B and C in Hungary. This study summarizes the experiences of nucleic acid amplification technology (NAT) screening of the first 16 months.

Methods

The study was conducted from 5 June 2018 to 30 September 2019 in two phases. During the first 7 months of the study, the NAT tests were performed in parallel with serology. The yields of the methods were compared. After the initial seven months, only seronegative samples were tested by NAT. NAT tests were performed in minipools of 96.

Results

In this 16‐month period, nearly 400 000 donations were screened by NAT. During the first phase, almost 150 000 samples were tested in parallel by serology and NAT screening. NAT screening during Phase I failed to identify 4 HCV‐ and 1 HBV‐reactive donations. In the second phase, about 245 000 seronegative samples were screened, with only one HBV reactive yield.

Conclusions

Nucleic acid amplification technology testing proven to be an optimal diagnostic adjunct to serological screening, since it can help to identify early window period infections and occult hepatitis B infections. According to our experience however, the used pooling strategy represents a dilution rate of nucleic acid targets, which makes identifying these types of infections difficult. According to our cost–benefit analysis, reducing the pool size to 60 would result in a 60% sensitivity increase, at the expense of increasing the daily costs by 25%.
Comparison of murine behavioural and physiological responses after forced exercise by electrical shock versus manual prodding
Authors: Khataei Tahsin , Romig‐Martin Sara A. , Harding Anne Marie S. , Radley Jason J. , Benson Christopher J.
Published: February 2021

New Findings

What is the central question of this study?

Forced treadmill exercise using electrical shock is the most common technique in rodent exercise studies. Here, we examined how the use of electrical shock during forced treadmill exercise affects behavioural and physiological responses in comparison to a novel non‐electrical shock technique.

What is the main finding and its importance?

In comparison to mice that underwent traditional treadmill running induced by electrical shock, mice that underwent forced running using a novel technique involving gentle prodding to induce running showed: (i) higher locomotor activity; (ii) less anxiety‐like behaviour; and (iii) altered exercise‐induced muscle pain immediately after exercise.

Animal models of exercise have been useful to understand underlying cellular and molecular mechanisms. Many studies have used methods of exercise that are unduly stressful (e.g., electrical shock to force running), potentially skewing results. Here, we compared physiological and behavioural responses of mice after exercise induced using a prodding technique that avoids electrical shock versus a traditional protocol using electrical shock. We found that exercise performance was similar for both techniques; however, the shock group demonstrated significantly lower locomotor activity and higher anxiety‐like behaviour. We also observed divergent effects on muscle pain; the prodding group showed hyperalgesia immediately after exercise, whereas the shock group showed hypoalgesia. Corticosterone concentrations were elevated to a similar extent for both groups. In conclusion, mice that were exercised without shock generated similar maximal exercise performance, but postexercise these mice showed an increase in locomotor activity, less anxiety‐like behaviour and altered muscle pain in comparison to mice that exercised with shock. Our data suggest that running of mice without the use of electrical shock is potentially less stressful and might be a better technique to study the physiological and behavioural responses to exercise.
Acompañamiento espiritual virtual: alcances y límites
Authors: Velásquez Camelo, SDB Edgar Enrique
Published: February 2021

La virtualización de las dinámicas de interacción social del mundo actual ha constituido diversas formas de relación entre las personas que hacen parte de la sociedad red. El diálogo, el compartir espontáneo, una conversación tienen su escenario de acción en los procesos de socialización que se llevan a cabo desde las plataformas digitales de comunicación. También, las dinámicas en torno de la experiencia de fe se han virtualizado y con ella las dimensiones de la pastoral de la Iglesia (kerigmática, comunitaria, diaconía, litúrgica y la catequesis); esto nos lleva a pensar la posibilidad del acompañamiento espiritual virtual como una acción pastoral de la Iglesia dirigida a las personas que, profesando la fe en Cristo Jesús, permanecen en la red. El objetivo de este artículo es presentar una reflexión que dé cuenta de los alcances y límites del acompañamiento espiritual virtual en la búsqueda personal del sentido de la existencia y la maduración de la vida de fe; así mismo, establecer las condiciones de posibilidad que llevan a plantear la viabilidad de direccionar procesos de acompañamiento espiritual por medio de las redes sociales que facilitan el diálogo, la cultura del encuentro y la participación activa de las personas en la sociedad red. Los alcances de dicha modalidad de acompañamiento están determinados por el grado de vinculación vital y referencial que establecen las personas por medio de los dispositivos electrónicos, y los límites están demarcados por la capacidad de tomar distancia del mundo virtual, es decir, el saber integrar en la existencia, de forma armónica, la representación virtual-real como actual-real del mundo. Todo esto en orden a enriquecer las prácticas eclesiales en la cultura de la virtualidad real y, además, legitimar la reflexión ciberteológica que tiene un estatuto epistemológico genuino que emerge en la relación integral entre fe, razón y vida.
Measurements of the correlation of the frequency-difference autoproduct with acoustic and predicted-autoproduct fields in the deep ocean
Authors: Geroski David J. , Dzieciuch Matthew A. , Dowling David R.
Published: February 2021

Frequency-domain spatial-correlation analysis of recorded acoustic fields is typically limited to the bandwidth of the recordings. A previous study [Lipa, Worthmann, and Dowling (2018) J. Acoust. Soc. Am. 143(4), 2419–2427] suggests that limiting such analysis to in-band frequencies is not strictly necessary in a Lloyd's mirror environment. In particular, below-band field information can be retrieved from the frequency-difference autoproduct, a quadratic product of measured complex pressure-field amplitudes from two nearby frequencies. The frequency-difference autoproduct is a surrogate field that mimics a genuine acoustic field at the difference frequency. Here, spatial-correlation analysis is extended to deep-ocean acoustic fields measured during the PhilSea10 experiment. The frequency-difference autoproduct, at difference frequencies from 0.0625 to 15 Hz, is determined from hundreds of Philippine Sea recordings of 60 or 100 Hz bandwidth signals with center frequencies from 172.5 to 275 Hz broadcast to a vertical receiving array 129–450 km away. The measured autoproducts are cross correlated along the array with predicted acoustic fields and with predicted autoproduct fields at corresponding below-band frequencies. Stable measured cross correlations as high as 80%–90% are found at the low end of the investigated difference-frequency range, with consistent correlation loss due to mismatch at the higher below-band frequencies.
Noninvasive imaging and quantification of bile salt hydrolase activity: From bacteria to humans
Authors: Khodakivskyi Pavlo V. , Lauber Christian L. , Yevtodiyenko Aleksey , Bazhin Arkadiy A. , Bruce Stephen , Ringel-Kulka Tamar , Ringel Yehuda , Bétrisey Bertrand , Torres Joana , Hu Jianzhong , Chou Chieh Jason , Goun Elena A.
Published: February 2021

Novel optical probes allow quantification of bile salt hydrolase activity in bacteria, clinical fecal samples, mice, and humans.
A single-nucleotide change underlies the genetic assimilation of a plastic trait
Authors: Vigne Paul , Gimond Clotilde , Ferrari Céline , Vielle Anne , Hallin Johan , Pino-Querido Ania , El Mouridi Sonia , Mignerot Laure , Frøkjær-Jensen Christian , Boulin Thomas , Teotónio Henrique , Braendle Christian
Published: February 2021

A single-nucleotide change underlies the transition from environmentally induced to genetically encoded matricidal hatching.
Digital light 3D printing of customized bioresorbable airway stents with elastomeric properties
Authors: Paunović Nevena , Bao Yinyin , Coulter Fergal Brian , Masania Kunal , Geks Anna Karoline , Klein Karina , Rafsanjani Ahmad , Cadalbert Jasmin , Kronen Peter W. , Kleger Nicole , Karol Agnieszka , Luo Zhi , Rüber Fabienne , Brambilla Davide , von Rechenberg Brigitte , Franzen Daniel , Studart André R. , Leroux Jean-Christophe
Published: February 2021

Customized bioresorbable airway stents with elasticity similar to silicone were 3D printed by digital light processing.
Active Hexose-Correlated Compound Restores Gene Expression and Protein Secretion of Protective Cytokines of Immune Cells in a Murine Stress Model during Chlamydia muridarum Genital Infection
Authors: Belay Tesfaye , Sahu Rajnish , Martin Elisha , Brown Kristin , Rolen Courtney , Hankins Shomonique , Punturi Brianna , Patterson Maya , Chambers Chase , Kirby Brandon , Butchar Jonathan
Published: February 2021

Chlamydia trachomatis
genital infection is the most common bacterial sexually transmitted disease worldwide. Previously, we reported that cold-induced stress results in immune suppression of mice that subsequently leads to increased intensity of
Chlamydia muridarum
genital infection.
Evaluating a New Class of AKT/mTOR Activators for HIV Latency-Reversing Activity
Ex Vivo
and
In Vivo
Authors: Gramatica Andrea , Schwarzer Roland , Brantley William , Varco-Merth Benjamin , Sperber Hannah S. , Hull Philip A. , Montano Mauricio , Migueles Stephen A. , Rosenthal Danielle , Hogan Louise E. , Johnson Jeffrey R. , Packard Thomas A. , Grimmett Zachary W. , Herzig Eytan , Besnard Emilie , Nekorchuk Michael , Hsiao Feng , Deeks Steven G. , Snape Michael , Kiernan Bernard , Roan Nadia R. , Lifson Jeffrey D. , Estes Jacob D. , Picker Louis J. , Verdin Eric , Krogan Nevan J. , Henrich Timothy J. , Connors Mark , Ott Melanie , Pillai Satish K. , Okoye Afam A. , Greene Warner C.
Published: February 2021

If combined with immune therapeutics, latency-reversing agents (LRAs) have the potential to reduce the size of the reservoir sufficiently that an engineered immune response can control the virus in the absence of antiretroviral therapy. We have identified a new class of LRAs that do not induce T-cell activation and that are able to potentiate, rather than inhibit, CD8
+
T and NK cell cytotoxic effector functions.
Supplemental Material: The Parker Quarry Lagerstätte of Vermont—The first reported Burgess Shale–type fauna rediscovered
Authors: Pari Giovanni , Briggs Derek , al. et
Published: February 2021

Material and methods, and data on sedimentology, geochemistry, and fossil numbers.
Supplemental Material: Homeostatic response of Aptian gymnosperms to changes in atmospheric CO2 concentrations
Authors: Mora German , al. et
Published: February 2021

Supplemental tables with results and data, and supplemental figures of chromatograms and chemical structures of identified terpenoids.
Supplemental Material: Subduction erosion and crustal material recycling indicated by adakites in central Tibet
Authors: Yang Zong-Yong , WANG QIANG , al. et
Published: February 2021

Supplemental figures, analytical methods and results, and data and results tables.
Supplemental Material: Secular variations of magma source compositions in the North Patagonian batholith from the Jurassic to Tertiary: Was mélange melting involved?
Authors: Castro A. , al. et
Published: February 2021

Geochemical and geochronologic data.
Contrast sensitivity function in patients with macular disease and good visual acuity
Authors: Wai Karen M , Vingopoulos Filippos , Garg Itika , Kasetty Megan , Silverman Rebecca F , Katz Raviv , Laíns Inês , Miller Joan W , Husain Deeba , Vavvas Demetrios G , Kim Leo A , Miller John B
Published: February 2021

Introduction

Contrast sensitivity function (CSF) may better estimate a patient’s visual function compared with visual acuity (VA). Our study evaluates the quick CSF (qCSF) method to measure visual function in eyes with macular disease and good letter acuity.

Methods

Patients with maculopathies (retinal vein occlusion, macula-off retinal detachment, dry age-related macular degeneration and wet age-related macular degeneration) and good letter acuity (VA ≥20/30) were included. The qCSF method uses an intelligent algorithm to measure CSF across multiple spatial frequencies. All maculopathy eyes combined and individual macular disease groups were compared with healthy control eyes. Main outcomes included area under the log CSF (AULCSF) and six CS thresholds ranging from 1 cycle per degree (cpd) to 18 cpd.

Results

151 eyes with maculopathy and 93 control eyes with VA ≥20/30 were included. The presence of a maculopathy was associated with significant reduction in AULCSF (β: −0.174; p<0.001) and CS thresholds at all spatial frequencies except for 18 cpd (β: −0.094 to −0.200 log CS, all p<0.01) compared with controls. Reductions in CS thresholds were most notable at low and intermediate spatial frequencies (1.5 cpd, 3 cpd and 6 cpd).

Conclusion

CSF measured with the qCSF active learning method was found to be significantly reduced in eyes affected by macular disease despite good VA compared with healthy control eyes. The qCSF method is a promising clinical tool to quantify subtle visual deficits that may otherwise go unrecognised by current testing methods.