bluuebunny/crossref_metadata_2025 huggingface dataset:
Inactivation and Recovery of High Quality RNA From Positive SARS-CoV-2 Rapid Antigen Tests Suitable for Whole Virus Genome Sequencing
Authors: Macori Guerrino , Russell Tristan , Barry Gerald , McCarthy Siobhán C. , Koolman Leonard , Wall Patrick , Sammin Donal , Mulcahy Grace , Fanning Séamus
Published: May 2022

The diagnostic protocol currently used globally to identify Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is RT-qPCR. The spread of these infections and the epidemiological imperative to describe variation across the virus genome have highlighted the importance of sequencing. SARS-CoV-2 rapid antigen diagnostic tests (RADTs) are designed to detect viral nucleocapsid protein with positive results suggestive of the presence of replicating virus and potential infectivity. In this study, we developed a protocol for recovering SARS-CoV-2 RNA from “spent” RADT devices of sufficient quality that can be used directly for whole virus genome sequencing. The experimental protocol included the spiking of RADTs at different concentrations with viable SARS-CoV-2 variant Alpha (lineage B.1.1.7), lysis for direct use or storage. The lysed suspensions were used for RNA extraction and RT-qPCR. In parallel, we also tested the stability of the viral RNA in the RADTs and the RNA extracted from the RADTs was used as a template for tiling-PCR and whole virus genome sequencing. RNA recovered from RADTs spiked with SARS-CoV-2 was detected through RT-qPCR with Ct values suitable for sequencing and the recovery from RADTs was confirmed after 7 days of storage at both 4 and 20°C. The genomic sequences obtained at each time-point aligned to the strain used for the spiking, demonstrating that sufficient SARS-CoV-2 viral genome can be readily recovered from positive-RADT devices in which the virus has been safely inactivated and genomically conserved. This protocol was applied to obtain whole virus genome sequence from RADTs ran in the field where the omicron variant was detected. The study demonstrated that viral particles of SARS-CoV-2 suitable for whole virus genome sequencing can be recovered from positive spent RADTs, extending their diagnostic utility, as a risk management tool and for epidemiology studies. In large deployment of the RADTs, positive devices could be safely stored and used as a template for sequencing allowing the rapid identification of circulating variants and to trace the source and spread of outbreaks within communities and guaranteeing public health.
Social Contacts and Transmission of COVID-19 in British Columbia, Canada
Authors: Ringa Notice , Iyaniwura Sarafa A. , David Samara , Irvine Mike A. , Adu Prince , Spencer Michelle , Janjua Naveed Z. , Otterstatter Michael C.
Published: May 2022

Background

Close-contact rates are thought to be a driving force behind the transmission of many infectious respiratory diseases. Yet, contact rates and their relation to transmission and the impact of control measures, are seldom quantified. We quantify the response of contact rates, reported cases and transmission of COVID-19, to public health contact-restriction orders, and examine the associations among these three variables in the province of British Columbia, Canada.

Methods

We derived time series data for contact rates, daily cases and transmission of COVID-19 from a social contacts survey, reported case counts and by fitting a transmission model to reported cases, respectively. We used segmented regression to investigate impacts of public health orders; Pearson correlation to determine associations between contact rates and transmission; and vector autoregressive modeling to quantify lagged associations between contacts rates, daily cases, and transmission.

Results

Declines in contact rates and transmission occurred concurrently with the announcement of public health orders, whereas declines in cases showed a reporting delay of about 2 weeks. Contact rates were a significant driver of COVID-19 and explained roughly 19 and 20% of the variation in new cases and transmission, respectively. Interestingly, increases in COVID-19 transmission and cases were followed by reduced contact rates: overall, daily cases explained about 10% of the variation in subsequent contact rates.

Conclusion

We showed that close-contact rates were a significant time-series driver of transmission and ultimately of reported cases of COVID-19 in British Columbia, Canada and that they varied in response to public health orders. Our results also suggest possible behavioral feedback, by which increased reported cases lead to reduced subsequent contact rates. Our findings help to explain and validate the commonly assumed, but rarely measured, response of close contact rates to public health guidelines and their impact on the dynamics of infectious diseases.
Connecting Scientometrics: Dimensions as a Route to Broadening Context for Analyses
Authors: Porter Simon J. , Hook Daniel W.
Published: May 2022

Modern cloud-based data infrastructures open new vistas for the deployment of scientometric data into the hands of practitioners. These infrastructures lower barriers to entry by making data more available and compute capacity more affordable. In addition, if data are prepared appropriately, with unique identifiers, it is possible to connect many different types of data. Bringing broader world data into the hands of practitioners (policymakers, strategists, and others) who use scientometrics as a tool can extend their capabilities. These ideas are explored through connecting Dimensions and World Bank data on Google BigQuery to study international collaboration between countries of different economic classification.
Exploring the Notion of Literacy Within Physical Literacy: A Discussion Paper
Authors: Durden-Myers Elizabeth J. , Bartle Gillian , Whitehead Margaret E. , Dhillon Karamjeet K.
Published: May 2022

The concept of physical literacy is continuing to gain traction internationally. This increasing interest has also given rise to concerns about the use, interpretation and meaning of the term “literacy” within the context of physical literacy. This paper explores the development of the terms literate, illiterate, literacy, and illiteracy identifying their historical origin and contemporary meaning. This provides the backdrop to explore the use of the term literacy within the context of physical literacy. In the final part of this introductory section the recent popularity of the literacies movement is explored. Our discussion identifies key intersections and areas of tension associated with the use, interpretation and meaning of literacy in the context of physical literacy. We adopt Whitehead's philosophy of physical literacy and discussion is informed further by Derrida's notion of differance, and Barad's challenge to singular representations of concepts. Once harnessing these concepts, we reach a juncture of an in-between space; entry points of nonidentity (sameness) and points where multiple effects of difference are created. Key discussion topics include: discourse, language and interpretations of literacy; in/tangibility of literacy; capturing literacy; literacy as a process or a product; connotations of the terms literate and illiterate; neoliberalism and literacy and finally literacy as learning. We believe that when understood as the productive and meaningful interaction with/in/through the world, literacy is still the appropriate term within the context of physical literacy. Our discussion leads us to conclude that as embodied individuals, physical literacy is often the literacy through which other literacies have to pass. Through physical activity individuals can not only nurture their own physical literacy but also contribute toward a global or holistic literacy that helps us navigate, connect and make sense of ourselves, others and the world around us. However, the paper acknowledges that this meaning is not always grasped with the historical understanding of literacy as well as it's translations into other languages presenting challenges in articulating the intended use, meaning and connotations of the contemporary understanding of physical literacy.
Effect of Oral Chinese Herbal Preparations Regulating Intestinal Flora on Lipid Metabolism Disorders in Patients: A Meta-Analysis of Controlled Clinical Studies
Authors: Gong Wenqian , Zhang Wuguang , Chang Chunyang
Published: May 2022

Background

Lipid metabolism disorders can damage human health, and the changes in human intestinal flora are closely related to lipid metabolism disorders. Traditional Chinese medicine (TCM) can play a role in regulating intestinal flora and balancing intestinal microecology. In this meta-analysis, the role of oral preparations of TCM that regulate intestinal flora, in the prevention and treatment of lipid metabolism disorders, was systematically evaluated.

Methods

The databases CBM, Pubmed, Embase, CNKI, Wanfang, and Google Scholar were searched by rapid matching of keywords to obtain clinical controlled studies related to oral preparations of TCMs regulating intestinal flora. After screening and quality evaluation, meta-analysis was performed using Review Manager 5.3 software.

Results

Total of 835 patients were enrolled in the 10 articles included in this study. Meta-analysis showed that TCM intervention could reduce the level of total cholesterol (TC) in patients with abnormal lipid metabolism [mean difference (MD) = −0.61, 95% confidence interval (95%CI) (−0.80, −0.42), p < 0.00001], reduce triacylglycerol (TG) level [MD = −0.46, 95%CI (−0.60, −0.33), p < 0.00001], increase high-density lipoprotein (HDL) level [MD = 0.25, 95%CI (0.17, 0.34), p < 0.00001], reduce the number of intestinal enterobacteria [MD = −0.64, 95%CI (−0.79, −0.49), p < 0.00001], reduce the number of enterococci [MD = −1.14, 95%CI (−1.66, −0.63), p < 0.00001], increase the number of intestinal lactobacillus [MD = 0.41, 95%CI (0.09, 0.74), p = 0.01], and increase the number of intestinal bifidobacteria [MD = 0.94, 95%CI (0.20, 1.68), p = 0.01].

Conclusion

The application of oral preparations of TCMs that regulate intestinal flora, in the prevention and treatment of lipid metabolism disorders, can increase the colonization of beneficial bacteria in the intestine of patients, inhibit the growth of harmful bacteria, and restore the intestinal microecological balance, thus indirectly acting on the regulation of blood lipids in patients and contributing to the recovery of dyslipidemia.
Expression of miR-4739 in Gastric cancer and its Relationship with Clinical Pathological Features of Patients
Authors: Wei Jiaxing , Li Jun , Geng Dong , Peng Yiling , Yang Bin , Wu Huixian , Zhou Yun
Published: May 2022

Objective

To investigate the expression level of miR-4739 in gastric cancer (GC), analyze its diagnostic value in GC and the relationship with clinical pathological characteristics, and analyze its impact on the prognosis of patients.

Methods

A total of 96 patients with GC who underwent radical gastrectomy in our hospital from March 2017 to June 2021 were selected. GC tissues from all patients were collected, and normal tissues adjacent to cancer were collected as controls. The expression level of miR-4739 in tissues was detected, the relationship between miR-4739 and different pathological features was analyzed, and the diagnostic value of miR-4739 in GC was analyzed. All patients were followed up after the operation, and the survival time of the patients was set as from the day of the first operation to 1 d when the patients died or the follow-up ended.

Results

The relative expression level of miR-4739 in the GC tissue was (0.39 ± 0.06), lower than that in the paracancerous tissue (1.18 ± 0.19) (P < 0.05). The AUC of miR-4739 in the diagnosis of GC was 0.705. When the Youden index was 0.320 and the optimal cutoff value was 0.37, the sensitivity was 95.30% and the specificity was 36.70%. The expression level of miR-4739 in our patient was related to the differentiation degree, lymph node metastasis, tumor diameter, and TNM stage (P < 0.05). During the follow-up period, 26 of 96 patients died, and the survival rate was 72.92% (26/96). The median survival time was 29 months in the miR-4739 LE group, which was shorter than 39 months in the miR-4739 HE group (P < 0.05). Univariate analysis showed that age, degree of differentiation, lymph node metastasis, tumor diameter, TNM staging, and miR-4739 expression were all related to the prognosis of the patient (P < 0.05). Multivariate analysis showed that differentiation degree, lymph node metastasis, tumor diameter, TNM staging, and miR-4739 expression were all independent factors affecting the prognosis of the patients (P < 0.05).

Conclusion

The expression of miR-4739 in GC tissue was down-regulated, and its level was related to the degree of differentiation, lymph node metastasis, tumor diameter, and TNM stage. The expression level of miR-4739 has certain diagnostic value for patients with GC, and the prognosis of patients in LE group was worse than that in HE group.
A Review of Fetal Bovine Serum in the Culture of Mesenchymal Stromal Cells and Potential Alternatives for Veterinary Medicine
Authors: Pilgrim Cara R. , McCahill Kiera A. , Rops Jenna G. , Dufour Jaustin M. , Russell Keith A. , Koch Thomas G.
Published: May 2022

Fetal bovine serum (FBS) remains widely used as a supplement in cell culture media used in the isolation and expansion of mesenchymal stromal cells (MSC) despite longstanding practical, clinical, and ethical concerns over its use. As a result, research on alternative culture media supplement solutions that conserve crucial MSC characteristics has become increasingly relevant. Species-specific supplements and serum-free media such as platelet lysate or chemically defined media have been assessed for their effect in MSC cultures regarding proliferation, differentiation, and immunomodulatory capacity. While none of the alternatives offer a complete solution in replacing traditional FBS supplemented media for culturing MSCs for all species, short-term or transitional use of FBS-free media can perform equally well and could address some of the concerns over the use of FBS.
Effects of Weaning Age on Plasma Biomarkers and Growth Performance in Simmental Calves
Authors: Ferronato Giulia , Cattaneo Luca , Trevisi Erminio , Liotta Luigi , Minuti Andrea , Arfuso Francesca , Lopreiato Vincenzo
Published: May 2022

Weaning plays a key role in health status and future performance of calves. The aim of this study was to investigate the effects of weaning age (Wa), early (45 d, EW) or conventional (60 d, CW), on growth performance and metabolic profile of ten Simmental calves (5 EW and 5 CW calves). Daily intake of milk and calf starter was recorded. Blood samples and measurements of body weight (BW), heart girth (HG), and wither height (WH) were collected at −25, −15, 0, 6, and 20 days relative to weaning. Growth performances (BW, HG, WH) were affected by Wa, resulting lower in EW calves compared with CW calves (p < 0.05). Average daily gain was affected by overall Wa and Time but also by the interaction Wa × Time (p < 0.05). EW calves had lower paraoxonase and higher oxidation protein products levels, lower glucose levels in the post-weaning period, lower Ca and cholesterol levels at 20 d after weaning, and higher GGT activity at −25 d from weaning (p < 0.05). A significant interaction effect between Wa and Time was reached for glucose, Ca, cholesterol. In conclusion, weaning Simmental calves at approximately six weeks of age might not affect inflammatory status and liver functionality after weaning. As secondary outcome, even though the low number of animals could represent a limitation, the average daily gain obtained by Simmental calves weaned at 45 d supported this strategy (despite the lower body weight at weaning and after was due only to the age difference of 15 days). Hence, in order to reduce rearing costs, early weaning for Simmental calves (dual-purpose breed, milk and beef) might not jeopardize calf development, as long as calves can reach body gains as reported in the present study.
African Swine Fever (ASF) Trend Analysis in Wild Boar in Poland (2014–2020)
Authors: Frant Maciej Piotr , Gal-Cisoń Anna , Bocian Łukasz , Ziętek-Barszcz Anna , Niemczuk Krzysztof , Szczotka-Bochniarz Anna
Published: May 2022

African swine fever (ASF) is a lethal hemorrhagic disease of Suidae, i.e., domestic pigs and wild boars. The disease was introduced to Poland in 2014 and is now present in the wild boar population. Appropriate ASF prevention requires further research for answers to fundamental questions about the importance of vectors in virus transmission, the impact of environmental factors on the presence of ASFV in wild boar habitats, and the role of survivors as potential virus carriers and their part in the potential endemicity of ASF. In order to analyze the changes in the molecular and serological prevalence of ASFV in wild boar population in Poland, real-time PCR and ELISA/IPT tests were conducted. In the analyzed period (2014–2020), most of the ASF-positive wild boars were molecular/virus-positive, however, over the years the percentage and the number of seropositive animals has increased. At the beginning of the epidemic, the disease was limited to a small area of the country. Since then, it has spread to new provinces of Poland. From the beginning and until today, most notifications of ASF-positive wild boars were for carcasses (passive surveillance), however, the number of serologically positive animals is still increasing. Despite the fact that notifications of ASF outbreaks are still being received near the eastern border of Poland, the old ASF area seems to be limited mainly to ASF serologically positive animals, which may indicate the beginning of ASF endemicity in Poland.
Antimicrobial Susceptibility of Enterococcus Isolates from Cattle and Pigs in Portugal: Linezolid Resistance Genes optrA and poxtA
Authors: Gião Joana , Leão Célia , Albuquerque Teresa , Clemente Lurdes , Amaro Ana
Published: May 2022

Enterococci are part of the commensal gut microbiota of mammals, with Enterococcus faecalis and Enterococcus faecium being the most clinically relevant species. This study assesses the prevalence and diversity of enterococcal species in cattle (n = 201) and pig (n = 249) cecal samples collected in 2017. Antimicrobial susceptibility profiles of E. faecium (n = 48) and E. faecalis (n = 84) were assessed by agar and microdilution methods. Resistance genes were screened through PCR and nine strains were analyzed by Whole Genome Sequencing. A wide range of enterococci species was found colonizing the intestines of pigs and cattle. Overall, the prevalence of resistance to critically important antibiotics was low (except for erythromycin), and no glycopeptide-resistant isolates were identified. Two daptomycin-resistant E. faecalis ST58 and ST93 were found. Linezolid-resistant strains of E. faecalis (n = 3) and E. faecium (n = 1) were detected. Moreover, oxazolidinone resistance determinants optrA (n = 8) and poxtA (n = 2) were found in E. faecalis (ST16, ST58, ST207, ST474, ST1178) and E. faecium (ST22, ST2138). Multiple variants of optrA were found in different genetic contexts, either in the chromosome or plasmids. We highlight the importance of animals as reservoirs of resistance genes to critically important antibiotics.
Characteristics and Impact of VOCs on Ozone Formation Potential in a Petrochemical Industrial Area, Thailand
Authors: Pinthong Nattaporn , Thepanondh Sarawut , Kultan Vanitchaya , Keawboonchu Jutarat
Published: May 2022

In this study, the ambient concentrations of volatile organic compounds (VOCs) were intensively measured from January 2012 to December 2016 using an evacuated canister and were analyzed using a gas chromatography/mass spectrophotometer (GC/MS) based on the US EPA TO-15 in the community and industrial areas of the largest petroleum refinery and petrochemical industrial complex in Map Ta Phut Thailand. The ternary diagram was used to identify the source of VOCs. Reactivity of VOCs on their ozone formation potential (OFP) were quantified by the maximum incremental reactivity coefficient method (MIR) and propylene-equivalent concentration methods. Results from the study revealed that aromatic hydrocarbon was the dominant group of VOCs greatly contributing to the total concentration of measured VOCs. Among the measured VOCs species, toluene had the highest concentration and contributed as the major precursor to ozone formation. The ternary analysis of benzene:toluene:ethybenzene ratios indicated that VOCs mainly originated from mobile sources and industrial processes. Within the industrial area, measured VOC concentration was dominated by halogenated hydrocarbons, and alkene was the highest contributor to ozone formation. The propylene-equivalent concentration method was also used to evaluate the reactivity of VOCs and their role in ozone formation, and secondly to support findings from the MIR method.
Flavonoids-Based Delivery Systems towards Cancer Therapies
Authors: Ferreira Miguel , Costa Diana , Sousa Ângela
Published: May 2022

Cancer is the second leading cause of death worldwide. Cervical cancer, for instance, is considered a major scourge in low-income countries. Its development is mostly associated with the human papillomavirus persistent infection and despite the availability of preventive vaccines, they are only widely administered in more developed countries, thus leaving a large percentage of unvaccinated women highly susceptible to this type of cancer. Current treatments are based on invasive techniques, being far from effective. Therefore, the search for novel, advanced and personalized therapeutic approaches is imperative. Flavonoids belong to a group of natural polyphenolic compounds, well recognized for their great anticancer capacity, thus promising to be incorporated in cancer therapy protocols. However, their use is limited due to their low solubility, stability and bioavailability. To surpass these limitations, the encapsulation of flavonoids into delivery systems emerged as a valuable strategy to improve their stability and bioavailability. In this context, the aim of this review is to present the most reliable flavonoids-based delivery systems developed for anticancer therapies and the progress accomplished, with a special focus on cervical cancer therapy. The gathered information revealed the high therapeutic potential of flavonoids and highlights the relevance of delivery systems application, allowing a better understanding for future studies on effective cancer therapy.
Review of Biomechanical Studies and Finite Element Modeling of Sternal Closure Using Bio-Active Adhesives
Authors: Al-Abassi Amatulraheem , Papini Marcello , Towler Mark
Published: May 2022

The most common complication of median sternotomy surgery is sternum re-separation after sternal fixation, which leads to high rates of morbidity and mortality. The adhered sternal fixation technique comprises the wiring fixation technique and the use of bio-adhesives. Adhered sternal fixation techniques have not been extensively studied using finite element analysis, so mechanical testing studies and finite element analysis of sternal fixation will be presented in this review to find the optimum techniques for simulating sternal fixation with adhesives. The optimal wiring technique should enhance bone stability and limit sternal displacement. Bio-adhesives have been proposed to support sternal fixation, as wiring is prone to failure in cases of post-operative problems. The aim of this paper is to review and present the existing numerical and biomechanical sternal fixation studies by reviewing common sternal closure techniques, adhesives for sternal closure, biomechanical modeling of sternal fixation, and finite element modeling of sternal fixation systems. Investigating the physical behavior of 3D sternal fixation models by finite element analysis (FEA) will lower the expense of conducting clinical trials. This indicates that FEA studies of sternal fixation with adhesives are needed to analyze the efficiency of this sternal closure technique virtually.
Farnesol-Loaded Nanoliposomes Inhibit Inflammatory Gene Expression in Primary Human Skeletal Myoblasts
Authors: Mückter Eva , Lozoya Maria , Müller Aline , Weissig Volkmar , Nourbakhsh Mahtab
Published: May 2022

There is a substantial unmet need for the treatment of skeletal muscle mass loss that is associated with aging and obesity-related increases in FFA. Unsaturated FFAs stimulate the inflammatory gene expression in human skeletal myoblasts (SkMs). Farnesol is a hydrophobic acyclic sesquiterpene alcohol with potential anti-inflammatory effects. Here, we created farnesol-loaded small unilamellar (SUVs) or multilamellar lipid-based vesicles (MLVs), and investigated their effects on inflammatory gene expression in primary human skeletal myoblasts. The attachment of SUVs or MLVs to SkMs was tracked using BODIPY, a fluorescent lipid dye. The data showed that farnesol-loaded SUVs reduced FFA-induced IL6 and LIF expression by 77% and 70% in SkMs, respectively. Farnesol-loaded MLVs were less potent in inhibiting FFA-induced IL6 and LIF expression. In all experiments, equal concentrations of free farnesol did not exert significant effects on SkMs. This report suggests that farnesol, if efficiently directed into myoblasts through liposomes, may curb FFA-induced inflammation in human skeletal muscle.
Cellular Stress Induces Nucleocytoplasmic Transport Deficits Independent of Stress Granules
Authors: Vanneste Joni , Vercruysse Thomas , Boeynaems Steven , Van Damme Philip , Daelemans Dirk , Van Den Bosch Ludo
Published: May 2022

Stress granules are non-membrane bound granules temporarily forming in the cytoplasm in response to stress. Proteins of the nucleocytoplasmic transport machinery were found in these stress granules and it was suggested that stress granules contribute to the nucleocytoplasmic transport defects in several neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). The aim of this study was to investigate whether there is a causal link between stress granule formation and nucleocytoplasmic transport deficits. Therefore, we uncoupled stress granule formation from cellular stress while studying nuclear import. This was carried out by preventing cells from assembling stress granules despite being subjected to cellular stress either by knocking down both G3BP1 and G3BP2 or by pharmacologically inhibiting stress granule formation. Conversely, we induced stress granules by overexpressing G3BP1 in the absence of cellular stress. In both conditions, nuclear import was not affected demonstrating that stress granule formation is not a direct cause of stress-induced nucleocytoplasmic transport deficits.
Tumor-Specific Imaging with Angiostamp800 or Bevacizumab-IRDye 800CW Improves Fluorescence-Guided Surgery over Indocyanine Green in Peritoneal Carcinomatosis
Authors: Josserand Véronique , Bernard Claire , Michy Thierry , Guidetti Mélanie , Vollaire Julien , Coll Jean-Luc , Hurbin Amandine
Published: May 2022

Complete surgical removal of lesions improves survival of peritoneal carcinomatosis and can be enhanced by intraoperative near-infrared fluorescence imaging. Indocyanine green (ICG) is the only near-infrared fluorescent dye approved for clinical use, but it lacks specificity for tumor cells, highlighting the need for tumor-selective targeting agents. We compared the tumor-specific near-infrared fluorescent probes Bevacizumab-IRDye 800CW and Angiostamp800, which target tumor angiogenesis and cancer cells, to ICG for fluorescence-guided surgery in peritoneal carcinomatosis of ovarian origin. The probes were administered to mice with orthotopic peritoneal carcinomatosis prior to conventional and fluorescence-guided surgery. The influence of neoadjuvant chemotherapy was also assessed. Conventional surgery removed 88.0 ± 1.2% of the total tumor load in mice. Fluorescence-guided surgery allowed the resection of additional nodules, enhancing the total tumor burden resection by 9.8 ± 0.7%, 8.5 ± 0.8%, and 3.9 ± 1.2% with Angiostamp800, Bevacizumab-IRDye 800CW and ICG, respectively. Interestingly, among the resected nodules, 15% were false-positive with ICG, compared to only 1.4% with Angiostamp800 and 3.5% with Bevacizumab-IRDye 800CW. Furthermore, conventional surgery removed only 69.0 ± 3.9% of the total tumor burden after neoadjuvant chemotherapy. Fluorescence-guided surgery with Angiostamp800 and Bevacizumab-IRDye 800CW increased the total tumor burden resection to 88.7 ± 4.3%, whereas ICG did not improve surgery at all. Bevacizumab-IRDye 800CW and Angiostamp800 better detect ovarian tumors and metastases than the clinically used fluorescent tracer ICG, and can help surgeons completely remove tumors, especially after surgery neoadjuvant chemotherapy.
Audiovisual Integration for Saccade and Vergence Eye Movements Increases with Presbycusis and Loss of Selective Attention on the Stroop Test
Authors: Chavant Martin , Kapoula Zoï
Published: May 2022

Multisensory integration is a capacity allowing us to merge information from different sensory modalities in order to improve the salience of the signal. Audiovisual integration is one of the most used kinds of multisensory integration, as vision and hearing are two senses used very frequently in humans. However, the literature regarding age-related hearing loss (presbycusis) on audiovisual integration abilities is almost nonexistent, despite the growing prevalence of presbycusis in the population. In that context, the study aims to assess the relationship between presbycusis and audiovisual integration using tests of saccade and vergence eye movements to visual vs. audiovisual targets, with a pure tone as an auditory signal. Tests were run with the REMOBI and AIDEAL technologies coupled with the pupil core eye tracker. Hearing abilities, eye movement characteristics (latency, peak velocity, average velocity, amplitude) for saccade and vergence eye movements, and the Stroop Victoria test were measured in 69 elderly and 30 young participants. The results indicated (i) a dual pattern of aging effect on audiovisual integration for convergence (a decrease in the aged group relative to the young one, but an increase with age within the elderly group) and (ii) an improvement of audiovisual integration for saccades for people with presbycusis associated with lower scores of selective attention in the Stroop test, regardless of age. These results bring new insight on an unknown topic, that of audio visuomotor integration in normal aging and in presbycusis. They highlight the potential interest of using eye movement targets in the 3D space and pure tone sound to objectively evaluate audio visuomotor integration capacities.
Clinical Manifestations of Body Memories: The Impact of Past Bodily Experiences on Mental Health
Authors: Gentsch Antje , Kuehn Esther
Published: May 2022

Bodily experiences such as the feeling of touch, pain or inner signals of the body are deeply emotional and activate brain networks that mediate their perception and higher-order processing. While the ad hoc perception of bodily signals and their influence on behavior is empirically well studied, there is a knowledge gap on how we store and retrieve bodily experiences that we perceived in the past, and how this influences our everyday life. Here, we explore the hypothesis that negative body memories, that is, negative bodily experiences of the past that are stored in memory and influence behavior, contribute to the development of somatic manifestations of mental health problems including somatic symptoms, traumatic re-experiences or dissociative symptoms. By combining knowledge from the areas of cognitive neuroscience and clinical neuroscience with insights from psychotherapy, we identify Clinical Body Memory (CBM) mechanisms that specify how mental health problems could be driven by corporeal experiences stored in memory. The major argument is that the investigation of the neuronal mechanisms that underlie the storage and retrieval of body memories provides us with empirical access to reduce the negative impact of body memories on mental health.
Molecular Profiles of Advanced Urological Cancers in the PERMED-01 Precision Medicine Clinical Trial
Authors: Billon Emilien , Gravis Gwenaelle , Guille Arnaud , Carbuccia Nadine , Adelaide Jose , Garnier Séverine , Finetti Pascal , Denicolaï Emilie , Sfumato Patrick , Brunelle Serge , Thomassin-Piana Jeanne , Pignot Géraldine , Walz Jochen , Chabannon Christian , Pakradouni Jihane , Sabatier Renaud , Vicier Cécile , Popovici Cornel , Mamessier Emilie , Gonçalves Anthony , Birnbaum Daniel , Chaffanet Max , Bertucci François
Published: May 2022

Introduction. The prognosis of advanced urological cancers (AUC) remains unfavorable, and few data are available regarding precision medicine. Methods: the PERMED-01 prospective clinical trial assessed the impact of molecular profiling in adults with refractory advanced solid cancer, in terms of number of patients with tumor actionable genetic alterations (AGA), feasibility, description of molecular alterations, treatment, and clinical outcome. We present here those results in the 64 patients enrolled with AUC. DNA extracted from a new tumor biopsy was profiled in real-time (targeted NGS, whole-genome array-comparative genomic hybridization), and the results were discussed during a weekly molecular tumor board meeting. Results: a complete molecular profile was obtained in 49 patients (77%). Thirty-eight (59%) had at least one AGA. Twelve (19%) received a matched therapy on progression, of which 42% had a PFS2/PFS1 ratio ≥ 1.3 versus 5% in the “non-matched therapy group” (n = 25). The objective response and disease control rates were higher in the “matched therapy group” (33% and 58%, respectively) than in the “non-matched therapy group” (13% and 22%), as was the 6-month OS (75% vs. 42%). Conclusion: the profiling of a newly biopsied tumor sample identified AGA in 59% of patients with AUC, led to “matched therapy” in 19%, and provided clinical benefit in 8%.
Hippo in Gastric Cancer: From Signalling to Therapy
Authors: Seeneevassen Lornella , Dubus Pierre , Gronnier Caroline , Varon Christine
Published: May 2022

The Hippo pathway is one of the most important ones in mammals. Its key functions in cell proliferation, tissue growth, repair, and homeostasis make it the most crucial one to be controlled. Many means have been deployed for its regulation, since this pathway is not only composed of core regulatory components, but it also communicates with and regulates various other pathways, making this signalisation even more complex. Its role in cancer has been studied more and more over the past few years, and it presents YAP/TAZ as the major oncogenic actors. In this review, we relate how vital this pathway is for different organs, and how regulatory mechanisms have been bypassed to lead to cancerous states. Most studies present an upregulation status of YAP/TAZ, and urge the need to target them. A focus is made here on gastric carcinogenesis, its main dysregulations, and the major strategies adopted and tested to counteract Hippo pathway disbalance in this disease. Hippo pathway targeting can be achieved by various means, which are described in this review. Many studies have tested different potential molecules, which are detailed hereby. Though not all tested in gastric cancer, they could represent a real interest.
In Vitro Human Cancer Models for Biomedical Applications
Authors: Choi Jane , Kozalak Gül , di Bari Ighli , Babar Quratulain , Niknam Zahra , Rasmi Yousef , Yong Kar
Published: May 2022

Cancer is one of the leading causes of death worldwide, and its incidence is steadily increasing. Although years of research have been conducted on cancer treatment, clinical treatment options for cancers are still limited. Animal cancer models have been widely used for studies of cancer therapeutics, but these models have been associated with many concerns, including inaccuracy in the representation of human cancers, high cost and ethical issues. Therefore, in vitro human cancer models are being developed quickly to fulfill the increasing demand for more relevant models in order to get a better knowledge of human cancers and to find novel treatments. This review summarizes the development of in vitro human cancer models for biomedical applications. We first review the latest development in the field by detailing various types of in vitro human cancer models, including transwell-based models, tumor spheroids, microfluidic tumor-microvascular systems and scaffold-based models. The advantages and limitations of each model, as well as their biomedical applications, are summarized, including therapeutic development, assessment of tumor cell migration, metastasis and invasion and discovery of key cancer markers. Finally, the existing challenges and future perspectives are briefly discussed.
Cardiac Evaluation of Exercise Testing in a Contemporary Population of Preschool Children: A New Approach Providing Reference Values
Authors: Latorre-Román Pedro Ángel , Martínez-Redondo Martínez , Salas-Sánchez Jesus , Consuegra-González Pedro José , Sarabia-Cachadiña Elena , Aragón-Vela Jerónimo , Párraga-Montilla Juan A.
Published: May 2022

The objective of this study was to evaluate cardiac autonomic function at rest, during maximal exercise, and in post-exercise recovery, to determine sex-specific and age-specific differences in resting heart rate (RHR), linear and spectral parameters of Heart Rate Variability (HRV), HRpeak, and heart rate recovery (HRR) after one and five minutes, in preschool children. This study involved a cohort of 167 healthy children (79 girls) aged 3 to 6 years that were selected from several schools in southern Spain. A 10 × 20 m test was conducted, and the cardiovascular response was recorded. No significant differences were found in all variables between the sexes. However, a significant reduction in RHR and an increase in HRR were found from age 4 to age 6. HRV parameters at rest were higher in older children. No associations between 10 × 20 m performance, weight status, and cardiac parameters were found. Simple linear regression analysis revealed that heart rate reserve (HRr), HRR5min, RMSSD, and HF were the variables that showed association with all HR parameters. There was also a significant correlation between HRr and HRR5min. In conclusion, cardiovascular autonomic function during rest, exercise, and recovery in Spanish preschool children was not influenced by sex, although older children showed greater cardiovascular modulation. Cardiorespiratory fitness status was not associated with HR response.
A Retrospective Analysis to Estimate the Burden of Invasive Pneumococcal Disease and Non-Invasive Pneumonia in Children <15 Years of Age in the Veneto Region, Italy
Authors: Barbieri Elisa , Porcu Gloria , Hu Tianyan , Petigara Tanaz , Senese Francesca , Prandi Gian Marco , Scamarcia Antonio , Cantarutti Luigi , Cantarutti Anna , Giaquinto Carlo
Published: May 2022

Despite advances in preventative interventions, invasive pneumococcal disease and pneumonia cause significant morbidity and mortality in children. We studied the annual incidence of pneumococcal-specific and syndromic invasive disease and non-invasive pneumonia in children <15 years of age during the early (2010–2013) and late (2014–2017) 13-valent pneumococcal conjugate vaccine (PCV13) periods in Veneto, Italy. In this retrospective observational study, pneumococcal-specific and syndromic invasive disease and non-invasive pneumonia cases were identified from several sources, including the Pedianet database. Interrupted time series analysis and Mann–Kendall tests were conducted to explore trends in incidence rates (IRs). Among 72,570 patients <15 years of age between 2010–2017, 88 episodes of pneumococcal-specific and syndromic invasive disease and 3926 episodes of non-invasive pneumonia were reported. Overall IR of pneumococcal-specific and syndromic invasive disease was 0.4/1000 person-years and did not change significantly (p = 0.46) throughout the study. Overall IR of non-invasive pneumonia was 10/1000 person-years and decreased significantly (−0.64, p = 0.026) over the study period. Following PCV13 introduction, the IRs of non-invasive pneumonia in children <15 years of age declined significantly, with no significant change in the IRs of pneumococcal-specific and syndromic invasive disease. There is a continuing clinical burden associated with pediatric pneumococcal diseases in Veneto, Italy.
MicroRaman Study of Nanostructured Ultra-Thin AlGaN/GaN Thin Films Grown on Hybrid Compliant SiC/Por-Si Substrates
Authors: Lenshin Aleksandr , Seredin Pavel , Goloshchapov Dmitry , Radam Ali O. , Mizerov Andrey
Published: May 2022

In our study, for the first time we demonstrate the advantages of using a compliant hybrid substrate of porSi/SiC to grow high-quality ultra-thin nanostructured AlxGa1−xN/GaN heterostructures using molecular beam epitaxy with plasma-activated nitrogen. Comparison of our experimental results obtained by micro-Raman spectroscopy, deconvolution, and the fitting of the experimental Raman spectra and subsequent calculations with information from already established literature sources show that the use of such a hybrid SiC/porSi substrate has a number of undeniable advantages for the growth of ultra-thin AlxGa1−xN/GaN nanoheterostructures without requiring the use of thick AIIIN buffer layers. Direct growth on a hybrid compliant substrate of SiC/porSi leads to a substantial relaxation in the elastic stresses between the epitaxial film, porous silicon, and silicon carbide, which consequently affects the structural quality of the ultra-thin AlxGa1−xN/GaN epitaxial layers. The experimental and computational data obtained in our work are important for understanding the physics and technology of AlxGa1−xN/GaN nanoheterostructures and will contribute to their potential applications in optoelectronics.
Comparison of the In Vitro Photodynamic Activity of the C1α and C1β Anomers of a Glucosylated Boron Dipyrromethene
Authors: Xiong Junlong , Yeung Ka-Wing , Wong Clarence T. T. , Fong Wing-Ping , Ng Dennis K. P.
Published: May 2022

Photodynamic therapy (PDT) is an established treatment modality for a range of superficial and localized cancers. There has been tremendous interest in the development of advanced photosensitizers that exhibit superior photophysical properties, high tumor selectivity, and improved pharmacokinetics. Glucose is one of the well-studied targeting moieties that can deliver various therapeutic agents to cancer cells selectively via the Warburg effect. However, the use of glucosylated photosensitizers for targeted PDT has remained little studied and to the best of our knowledge, the PDT effect of the positional isomers of these conjugates has never been compared. We report herein the preparation and photophysical properties of the C1α and C1β anomers of a glucosylated boron dipyrromethene-based photosensitizer. The cellular uptake and photocytotoxicity of both anomers were also studied and compared using A549 human lung carcinoma cells and HEK293 human embryonic kidney cells. Interestingly, the cellular uptake of the C1α anomer was approximately 2-fold higher than that of the C1β anomer regardless of the cell type and incubation time. The uptake pathway of both anomers was also studied. It was found that they were internalized through energy-dependent receptor/protein-mediated endocytosis rather than the well-known glucose transporters and sodium-driven glucose symporters.
Risk Stratification and Cancer Follow-Up: Towards More Personalized Post-Treatment Care in Canada
Authors: Urquhart Robin , Cordoba Wendy , Bender Jackie , Cuthbert Colleen , Easley Julie , Howell Doris , Kaal Julia , Kendell Cynthia , Radford Samantha , Sussman Jonathan
Published: May 2022

After treatment, cancer survivors require ongoing, comprehensive care to improve quality of life, reduce disability, limit complications, and restore function. In Canada and internationally, follow-up care continues to be delivered most often by oncologists in institution-based settings. There is extensive evidence to demonstrate that this model of care does not work well for many survivors or our cancer systems. Randomized controlled trials have clearly demonstrated that alternate approaches to follow-up care are equivalent to oncologist-led follow-up in terms of patient outcomes, such as recurrence, survival, and quality of life in a number of common cancers. In this paper, we discuss the state of follow-up care for survivors of prevalent cancers and the need for more personalized models of follow-up. Indeed, there is no one-size-fits-all solution to post-treatment follow-up care, and more personalized approaches to follow-up that are based on individual risks and needs after cancer treatment are warranted. Canada lags behind when it comes to personalizing follow-up care for cancer survivors. There are many reasons for this, including difficulty in determining who is best served by different follow-up pathways, a paucity of evidence-informed self-management education and supports for most survivors, poorly developed IT solutions and systems, and uneven coordination of care. Using implementation science theories, approaches, and methods may help in addressing these challenges and delineating what might work best in particular settings and circumstances.
Association between Vascular Calcification and Esophagojejunal Anastomotic Complications after Total Gastrectomy for Gastric Cancer: A Propensity-Matched Study
Authors: Lee Su-Lim , Jeon Chul-Hyo , Park Ki-Bum , Seo Ho-Seok , Lee Han-Hong
Published: May 2022

Esophagojejunal anastomosis (EJA) complications after total gastrectomy are related to significant morbidity and mortality. The aim of this study was to evaluate the association between arterial calcifications and EJA complications such as leak and stricture for gastric cancer. Between January 2014 and October 2019, 30 patients with EJA complications after total gastrectomy were enrolled and matched to 30 patients without complications through retrospective data review. Arterial calcification grade on preoperative computed tomography (CT) was reported in the abdominal aorta and superior mesenteric artery (SMA) as “absent”, “minor”, or “major”, and in the jejunal vascular arcade (JVA) and left inferior phrenic artery (LIPA) as “absent” or “present”. A Chi-square test was used to compare the variables between the two groups. p-Value < 0.050 was considered statistically significant. Among 30 patients, the numbers of patients with leak and stricture were 23 and seven, respectively. Aortic calcifications were not associated with EJA complications regardless of their grade (p = 0.440). Only major SMA calcifications were associated with EJA complications, as they were present in five patients (16.7%) in the complication group and absent in the non-complication group (p = 0.020). Major SMA calcifications were more related to anastomotic stricture than leak. Three (13.0%) out of 23 patients with leak and two (28.6%) out of seven with stricture had major SMA calcifications (p = 0.028). No calcifications were detected in the JVA or LIPA in any of the 60 patients. Major SMA calcifications were found to be associated with EJA complications, especially in stricture.