bluuebunny/crossref_metadata_2025 huggingface dataset:
How to achieve the sustainability of the seafood sector in the European Atlantic Area?
Authors: Ruiz-Salmón I , Laso J , Campos C , Fernández-Ríos A , Hoehn D , Margallo M , Irabien A , Aldaco R
Published: November 2021

Climate change, globalization or marine debris are on the spot of concerns for the most society. Particularly, fisheries are impacted by these and other issues. On the framework of the European Atlantic area, NEPTUNUS project (EAPA_576_2018) tries to provide opportunities for the transition to the circular economy of the seafood and aquaculture sectors by means of a consistent methodology for products eco-labelling and defining eco-innovation strategies. Furthermore, this project will provide key actions for resource efficiency based on life cycle thinking and the nexus water-energy-food, incorporating producers, policy makers and consumers in the decision-making process. This review addresses, therefore, the threats and challenges of the current Atlantic fisheries, the methodologies and actions to be face them and the expected results of the NEPTUNUS project
Transport electrification at all environmental costs? The case of large passenger duty-vehicles
Authors: Bouter A , Hache E , Sokhna Seck G
Published: November 2021

Electrification is often highlighted as the future for transportation sector as it is considered as a zero-tailpipe emission. However, environmental impacts related to battery electric vehicles (BEVs) exist. The aim of this article is to identify the trade-off between batteries’ weight and vehicle’s autonomy from an environmental perspective in the BEVs’ development as electrified mobility will consume more critical materials but reducing tailpipe emissions. Thus, a focus on climate change and resources has been done using a life cycle assessment (LCA) methodology. Large vehicles (D-segment) for BEVs and their fossil thermic counterparts have been assessed for two time horizons (2019, 2030) in Europe. Our linear programming world energy-transport model, TIAM-IFPEN, has been used in order to assess demand and import dependency on materials through to 2050. Results show that BEVs can generate higher impacts than their inherent conventional ones and that criticality assessment should be done in order to get a complete view of BEVs’ deployment.
Recycled concrete for foundation structure: LCA case study
Authors: Pešta J , Pavlo˚ T , Fořtová K , Řepka J
Published: November 2021

Concrete containing primary raw resources such as sand and gravel can be replaced by recycled aggregate concretes (RAC). But recycling processes are energy-consuming and thus energy resources are consumed. To investigate the resource consumption and overall environmental impact related to the life cycle of RAC, Life Cycle Assessment (LCA) was used to compare ten RAC foundation structures with two foundation structures containing just natural aggregate (NA). This paper presents the characteristics of two types of RAC for the foundation with various replacement rates of NA (30%, 50%, 100%). Various concrete mixtures were designed with the three replacement ratios of natural gravel, the two amount of cement and the two effective water-cement ratios. Unsurprisingly, the NA foundation structures have smaller crude oil consumption. The NAC I 16/20 foundation consumed 84 kg of crude oil. Contrarily, this foundation has the biggest consumption of natural aggregate (7.6 t). Moreover, the RAC foundation structures have beneficial impacts in the Metal depletion category. For example, the impact of the RAC I C30_V1 foundation is -31,7 kg Fe eq. Most of the RAC foundation structures demonstrated the overall environmental impact lower than NA foundation structures, suggesting that RAC could be suitable replacements for standard concretes.
Electroflotation of iron ore fines using biosurfactant
Authors: Simões Carolina , Rojas Ronald , Camarate Marcelo , Torem Maurício
Published: November 2021

Conventional flotation shows low recovery of the fine particles due to the low probability of bubble-particle adhesion and collision, what can be solved with the electroflotation process. Electroflotation uses oxygen and hydrogen microbubbles (<100µm) generated from water electrolysis. In addition, this process can become a biotechnology using a biosurfactant. The present work aims to evaluate the recovery of hematite fine particles from an iron ore using the electroflotation process with a biosurfactant obtained from Rhodococcus opacus. The tests were conducted with an iron ore (-38+20μm) in a Partridge-Smith modified electroflotation binary cell. The parameters used in these tests were current density (16 mA/cm2), agitation (300rpm), electrolyte concentration (0.2mol/L), conditioning time (5min) and flotation time (10 min). The pH range between 3 and 11, biosurfactant concentration (50 to 800mg/L) were evaluated and up to now, the results show that the electroflotation process was able to concentrate the hematite of the iron ore.
Evaluating the Microstructure of Photoluminescent Concrete Pavement Containing Strontium-Aluminate, Acrylic and Recycled Waste Glass
Authors: Seyab Maqsud Ahmed , Amin Shohel , Iqbal Rahat
Published: November 2021

This paper constructs the photoluminescent concrete pavement (PhotoCP) mixing the photoluminescent material (Strontium-Aluminate) with recycled waste glass and transparent acrylic to visible the neighbourhood streets without streetlights. The non-destructive analyses of photoluminescent materials were conducted using the X-Ray Fluorescence, X-Ray diffraction, and Scanning Electron Microscopy instruments to understand the behaviour of atoms in photoluminescent materials when they interact with radiation. The compressive strength test examined the load bearing capacity of PhotoCP. A 30cm x 230cm test bed was constructed at a neighbourhood street in Peshawar, Pakistan to assess the impact of photoluminescent materials on lighting the neighbourhood street. The non-destructive analyses and compressive strength test show that PCP specimens have good interlocking capability, structural strength and durability. The testbed experiment observed the illuminance of PhotoCP for a period of 6 to 8 hours with highest lumen intensity of 1-3 lux from sunset to 8:30 pm.
Heavy metal and fertility in a Tropical Oxisol amended with sewage sludge under Eucalyptus plantation
Authors: Cardoso Paulo H.S. , Mandu Thays S. , Florentino Antonio L. , Oliveira Rosana B. , Alleoni Luís R.F. , Alvares Clayton A. , Nogueira Thiago A.R. , Jani Arun D. , Capra Gian F. , Abreu-Junior Cassio H.
Published: November 2021

The objectives of our study were to evaluate i) the soil fertility and fractionation of Ba, Cd, Cu, and Zn in the topsoil layer (0-0.20 m depth); and ii) production and concentration and accumulation of Ba, Cd, Cu, and Zn in the components of Eucalyptus trees at 36 months after sewage sludge (SS) application, with or without mineral P fertilizer, compared to mineral fertilization. Application of SS (at N criteria) with P increased soil organic matter and heavy metal concentrations, which were mostly bound to the oxidic and organic matter fractions. SS provided Eucalyptus production and heavy metal concentrations and accumulation in the trunk, branches, and leaves similar to mineral fertilization for high wood production. The application of SS (at N criteria) supplied with P increased soil heavy metal, fertility, and Eucalyptus production, without risk of environmental contamination.
Exploring Secondary Markets to Improve Circularity: A comparative case study of photovoltaics and hard-disk drives
Authors: Watts Liam , Walzberg Julien , Carpenter Alberta , Heath Garvin A.
Published: November 2021

Each year renewable energy generation increases notably with solar panel installations, but these panels have a limited lifespan and will produce between 2 and 4 million metric tons of waste by 2040. Similarly, there are currently between 20 to 70 million hard-disk drives (HDDs) reaching end-of-life (EOL) annually. The circular economy (CE) strives to recycle and reuse materials that are rare and expensive to obtain, minimizing waste. However, studying the potential circularity of photovoltaics (PV) and HDDs requires various data, for instance, on the maturity of the secondhand markets. In this context, the objective of the present study is to identify the current state of secondhand PV and HDD markets. After conducting a literature review, an automated data collection process was set up for that purpose. The analysis of the literature and collected data assess the maturity of the secondhand PV modules and HDDs markets and highlight differences between them.
Providing a targeted algorithm for replacing customers’ Water meters aiming at reducing NRW: case study
Authors: Ebadati E , shafaghat R , Raji Asadabadi MJ , Majidaei H , Negharchi S M
Published: November 2021

Limited water resources, especially in Iran, which has an arid/semi-arid climate, highlight the need for accuracy in managing and controlling the consumption of this vital fluid. Although many approaches have been developed to reduce Non-Revenue Water (NRW) in water distribution systems, less attention has been paid to optimal prioritization for water meter replacement. In this research, an algorithm has been presented for the purposeful replacement of customers’ water meters to increase the company’s revenue. Gavankola village has been selected as a rural network in northern Iran with a high NRW rate (58%) as a case study. Examining the customers’ water consumption in 20 periods, it was found that after replacing the water meter, the billed metered consumption (BMC) doubled and the revenue from it increased up to 5 times. Moreover, the study of two economic indicators and NRW revealed that class C water meters are less economical than class B water meters, even though they more effectively reduce apparent losses.
The Effects of Airfoil Type and Wind Speed on the Aerodynamic Efficiency of Vertical Axis Wind Turbines
Authors: Najafi A , Biglarian M , Negharchi S M
Published: November 2021

This research focuses on improving the extraction of wind energy as one of the main renewable energy sources, in vertical axis wind turbines (VAWTs). In the current study, 5 turbine types with identical geometrical structures but with completely different blades have been analysed in various wind speeds. The numerical study was performed in two and three-dimensional (2D and 3D) modes using the finite volume method. The solution results were obtained in an unsteady state and assuming incompressible fluid flow. Also, k-? SST turbulence model was employed for modelling the turbulent flow. To ensure that the numerical results are valid, the numerical results were compared with experimental data, and it was found that the numerical and experimental results are in good compatibility. Among the simulated turbines, the S1046 airfoil had the maximum coefficient of performance, a larger operating range, and a higher average efficiency compared to other turbines. For all of the airfoils, the results showed that the coefficient of performance reduces in a specific range of rotor blade tip speed ratio. Since the 2D results were in good agreement with the 3D results, 2D simulations can be used in the designing and optimizing processes of VAWTs.
Small-scale agricultural grassland management can affect soil fungal community structure as much as continental scale geographic patterns
Authors: Fox A , Widmer F , Barreiro A , Jongen M , Musyoki M , Vieira Â , Zimmermann J , Cruz C , Dimitrova-Mårtensson L-M , Rasche F , Silva L , Lüscher A
Published: November 2021

A European transect was established, ranging from Sweden to the Azores, to determine the relative influence of geographic factors and agricultural small-scale management on the grassland soil microbiome. Within each of five countries (factor ‘Country’), which maximized a range of geographic factors, two differing growth condition regions (factor ‘GCR’) were selected: a favorable region with conditions allowing for high plant biomass production and a contrasting less favorable region with a markedly lower potential. Within each region, grasslands of contrasting management intensities (factor ‘MI’) were defined: intensive and extensive, from which soil samples were collected. Across the transect, ‘MI’ was a strong differentiator of fungal community structure, having a comparable effect to continental scale geographic factors (‘Country’). ‘MI’ was also a highly significant driver of bacterial community structure, but ‘Country’ was clearly the stronger driver. For both, ‘GCR’ was the weakest driver. Also at the regional level, strong effects of MI occurred on various measures of the soil microbiome (i.e. OTU richness, management-associated indicator OTUs), though the effects were largely regional-specific. Our results illustrate the decisive influence of grassland MI on soil microbial community structure, over both regional and continental scales, and, thus, highlight the importance of preserving rare extensive grasslands.
Call me by my name: unravelling the taxonomy of the gulper shark genus Centrophorus in the Mediterranean Sea through an integrated taxonomic approach
Authors: Bellodi Andrea , Benvenuto Anna , Melis Riccardo , Mulas Antonello , Barone Monica , Barría Claudio , Cariani Alessia , Carugati Laura , Chatzispyrou Archontia , Desrochers Monique , Ferrari Alice , Guallart Javier , Hemida Farid , Mancusi Cecilia , Mazzoldi Carlotta , Ramírez-Amaro Sergio , Rey Javier , Scannella Danilo , Serena Fabrizio , Tinti Fausto , Vella Adriana , Follesa Maria Cristina , Cannas Rita
Published: November 2021

The current shift of fishery efforts towards the deep sea is raising concern about the vulnerability of deep-water sharks, which are often poorly studied and characterized by problematic taxonomy. For instance, in the Mediterranean Sea the taxonomy of genus Centrophorus has not been clearly unravelled yet. Since proper identification of the species is fundamental for their correct assessment and management, this study aims at clarifying the taxonomy of this genus in the Mediterranean Basin through an integrated taxonomic approach. We analysed a total of 281 gulper sharks (Centrophorus spp.) collected from various Mediterranean, Atlantic and Indian Ocean waters. Molecular data obtained from cytochrome c oxidase subunit I (COI), 16S ribosomal RNA (16S), NADH dehydrogenase subunit 2 (ND2) and a portion of a nuclear 28S ribosomal DNA gene region (28S) have highlighted the presence of a unique mitochondrial clade in the Mediterranean Sea. The morphometric results confirmed these findings, supporting the presence of a unique and distinct morphological group comprising all Mediterranean individuals. The data strongly indicate the occurrence of a single Centrophorus species in the Mediterranean, ascribable to C. cf. uyato, and suggest the need for a revision of the systematics of the genus in the area.
Diagnosis and Management of Perineal Hernias
Authors: Jurkeviciute Digne , Dulskas Audrius
Published: November 2021

CASE SUMMARY:

A 72-year-old male patient presented to our outpatient clinic complaining with a perineal bulge one year after abdominoperineal excision for rectal cancer. He described a progressively enlarging bulge in the perineum causing a dull pain that was worse when sitting. On examination, the skin was intact, and a soft 7-cm hernia was identified that could be reduced into the pelvis but recurred immediately. Treatment options were discussed.
Efficacy and safety of aprotinin in paediatric cardiac surgery
Authors: Atasever Ayse Gulsah , Eerens Mathias , Van den Eynde Raf , Faraoni David , Rex Steffen
Published: November 2021

BACKGROUND

The relicensing of aprotinin in Europe and Canada has stimulated discussions on its usefulness in paediatric cardiac surgery.

OBJECTIVE

To systematically evaluate the available evidence on the efficacy and safety of aprotinin in paediatric cardiac surgery.

DESIGN

Systematic review of all randomised and observational studies comparing aprotinin with tranexamic acid, epsilon aminocaproic acid, placebo or no drug in paediatric cardiac surgery. Meta-analyses were performed on efficacy and safety outcomes.

DATA SOURCES

PubMed, Cochrane Central Register of Controlled Trials, Web of Science and Embase were searched from January 2000 to March 2021.

ELIGIBILITY CRITERIA

Studies that enrolled children under 18 years undergoing cardiac surgery with cardiopulmonary bypass.

RESULTS

Thirty-two studies enrolling a total of 63 894 paediatric cardiac procedures were included. Aprotinin significantly reduced total blood loss [mean difference −4.70 ml kg−1, 95% confidence interval (CI), −7.88 to −1.53; P = 0.004], postoperative transfusion requirements and the incidence of surgical re-exploration for bleeding [odds ratio (OR) 0.74, 95% CI, 0.56 to 0.97; P = 0.03]. Aprotinin had no effects on 30-day mortality (OR 1.02, 95% CI, 0.93 to 1.11; P = 0.73) and on other safety outcomes, except for the incidence of renal replacement therapy (RRT), which was significantly increased in patients given aprotinin (OR 1.29, 95% CI, 1.08 to 1.54; P = 0.006). Findings from observational and randomised controlled trials did not largely differ. A sub-group analysis in neonates showed that aprotinin significantly reduced packed red blood cell transfusions and the incidence of postoperative surgical re-exploration for bleeding and/or tamponade. When compared with lysine analogues, aprotinin was more effective at reducing bleeding and transfusion without increasing the risk of side effects.

CONCLUSION

This meta-analysis suggests that aprotinin is effective and well tolerated in paediatric cardiac surgery. Given the large heterogeneity of the results and the risk of selection bias in observational studies, large randomised controlled trials are warranted.
Factors associated with high placebo response in clinical studies of hot flashes: a meta-analysis
Authors: Miyazaki Kentaro , Kaneko Masayuki , Narukawa Mamoru
Published: November 2021

Importance:

High placebo response can often mask the evaluation of active treatment in clinical studies for women with hot flashes and potentially undermine the evaluation of new treatments.

Objective:

The aim of this meta-analysis was to determine the factors associated with high placebo response (defined as the reduction in the mean number of hot flash frequency from baseline) in randomized, controlled, double-blind studies enrolling women with hot flashes.

Evidence Review:

To identify eligible studies, Embase, MEDLINE, and BIOSIS Previews were searched for English-language articles published between April 1975 and August 2020. Placebo-controlled, double-blind, randomized studies that assessed changes in hot flash frequency were included if they satisfied the defined criteria. We conducted univariate and multivariate analyses using categorical and numerical data. Categorical data included the following variables and levels in brackets: active treatment type (hormone therapy /non- hormone therapy /complementary and alternative medicine), administration route (oral/non-oral), study region (in/excluded the US), breast cancer population (in/excluded), entry criteria of hot flash severity (moderate to severe only/all included), parallel or crossover study, placebo run-in period before treatment (yes/no), and menopausal status (postmenopausal only/include perimenopausal/include premenopausal). Numerical data included published year, pretreatment period duration, treatment period duration, number of sites, number of total participants, number of placebo participants, number of treatment arms, mean age, BMI, and hot flash frequency at baseline.

Findings:

Forty-three of the 802 identified publications were included in the review. Multivariate analysis identified three individual factors associated with high placebo response: treatment period duration, number of treatment arms, and BMI.

Conclusions and Relevance:

We identified several factors associated with high placebo response in clinical studies of women with hot flashes. Knowing these factors may enable proactive implementation of operational and analytic strategies that further aid in determining the true treatment effect of an intervention.
Opioid-sparing Strategies in Alloplastic Breast Reconstruction: A Systematic Review
Authors: Crystal Dustin T. , Ibrahim Ahmed M. S. , Blankensteijn Louise L. , Cuccolo Nicholas G. , Kazei Darya , Zitkovsky Helen S. , Lee Bernard T. , Lin Samuel J.
Published: November 2021

Introduction:

Pain and discomfort are frequently experienced following mastectomy with concomitant breast implant- or tissue expander-based alloplastic breast reconstruction (AlBR). Unfortunately, postoperative opioids have decreased efficacy in AlBR, short-term complication profiles, and are fraught by long-term dependence. This systematic review aims to identify opioid-sparing pain management strategies in AlBR.

Methods:

A systematic literature search of MEDLINE, Embase, Web of Science, and Cochrane Central Register was performed in September 2018. PRISMA guidelines were followed, and the review was prospectively registered in PROSPERO (CRD42018107911). The search identified 1184 articles. Inclusion criteria were defined as patients 18 years or older undergoing AlBR.

Results:

Fourteen articles were identified assessing opioid-sparing strategies in AlBR. This literature included articles evaluating enhanced recovery protocols (two), intercostal blocks (two), paravertebral blocks (four), liposomal bupivacaine (three), diclofenac (one), and local anesthesia infusion pumps (two). The literature included five randomized trials and nine cohort studies. Study characteristics, bias (low to high risk), and reporting outcomes were extensively heterogeneous between articles. Qualitative analysis suggests reduced opioid utilization in enhanced recovery after surgery (ERAS) pathways, paravertebral blocks, and use of liposomal bupivacaine.

Conclusions:

A variety of opioid-sparing strategies are described for pain management in AlBR. Multimodal analgesia should be provided via ERAS pathways as they appear to reduce pain and spare opioid use. Targeted paravertebral blocks and liposomal bupivacaine field blocks appear to be beneficial in sparing opioids and should be considered as essential components of ERAS protocols. Additional prospective, randomized trials are necessary to delineate the efficacy of other studied modalities.
Loose zonules in cataract surgery
Authors: Venkateswaran Nandini , Henderson Bonnie A.
Published: November 2021

Purpose of review

This review will focus on identifying causes of zonulopathy during cataract surgery and discuss various modalities for treatment.

Recent findings

There are multiple different options for capsular bag support in the setting of zonulopathy, including capsular or iris hooks, capsular tension rings as well as capsular tension segments (CTS). Surgical techniques on how to insert these devices are many and can be customized based upon the surgeon's preference and the patient's eye anatomy.

Recognizing zonular weakness is critical to achieve stable postoperative vision and avoid future complications. Depending on the degree of zonulopathy, various treatment options can be pursued, ranging from capsular tension hooks or iris hooks, capsular tension rings or sutured or scleral fixated CTS.
IX international curse of continuing formation in haemophilia and other congenital coagulopathies. The role of the Laboratory in coagulation disorders. Diagnosis of von Willebrand disease
Authors: Batlle Javier , Pérez-Rodríguez Almudena , Corrales Irene , Borràs Nina , Pinto Joana Costa , López-Fernández María Fernanda , Vidal Francisco
Published: November 2021

Von Willebrand disease (VWD) is the most frequent inherited bleeding disorder caused by quantitative or qualitative defects of von Willebrand factor (VWF). This protein far from simplicity constitutes a very complex molecular model, remaining unravelled yet many aspects of it, even though the VWF gene (VWF) was cloned already in 1985 and the structure of VWF well defined. VWD diagnosis is difficult to achieve in a significant proportion of patients due to both disease heterogeneity and limitations in existing test processes. The cornerstone of diagnosis relies on interpretation of VWF test results, the presence of clinical manifestations of bleeding, especially mucocutaneous, and (in most cases) a positive family history. However, even with a significant bleeding history, a family history may not be positive due to factors of incomplete penetrance and variable expressivity that affect genetic changes. The laboratory diagnosis of VWD can be difficult, as the disease is heterogeneous and an array of assays is required to describe the phenotype. Basic classification of quantitative (type 1 and 3) and qualitative (type 2 variants) VWD requires determination of VWF antigenic (VWF:Ag) levels and assaying of VWF ristocetin cofactor (VWF:RCo) activity. The latter is required for identifying and subtyping VWD, but the assay is poorly standardized. For that reason, novel VWF activity assays have been developed awaiting more extensive comparison data between different methodologies and requiring validation on larger patient series. The qualitative type 2 VWF deficiency can be further divided into four different subtypes (A, B, M and N) using specific assays that measure other activities or the size distribution of VWF multimers. However, frequently, it may be difficult to correctly classify the VWD phenotype, and genetic analysis is through mutation identification may provide a tool to clarify the disorder.
Reference values of mandibular condylar growth activity: a study of SUVmax with quantitative bone SPECT/CT
Authors: Lin Zefang , Xue Qianqian , Lin Rong , Yao Shaobo , Miao Weibing
Published: November 2021

Objective

To assess the condylar growth activity (CGA) with quantitative bone single photon emission computed tomography/computed tomography (SPECT/CT) to establish reference values of maximum standardized uptake value (SUVmax) and cutoff values for identifying active unilateral condylar hyperplasia (UCH) in different ages.

Methods

We analyzed the CGA of 58 UCH patients and that of 125 volunteers as a control group by SUVmax of quantitative bone SPECT/CT imaging. The SUVmax and the uptake difference between bilateral condyles among different age groups were analyzed. SUVmax cutoff values for detecting active condyle were calculated by receiver operating characteristic curve analysis.

Results

The condylar SUVmax in 10–19, 20–29, 30–39, 40–49 and 50–59 years old groups of volunteers were 6.24 ± 1.39, 4.76 ± 0.98, 3.23 ± 0.64, 3.00 ± 0.61 and 2.90 ± 0.53, respectively. The uptake difference between bilateral condyles in the control group was 3.84% ± 1.71%. The affected condylar SUVmax was significantly higher than that of the contralateral condyle in active UCH patients (6.03 ± 2.85 vs. 3.96 ± 1.07; Z = −5.264; P = 0.000). SUVmax of the affected condyles in active UCH patients was not statistically higher than condylar SUVmax in the corresponding age group (6.03 ± 2.85 vs. 5.50 ± 1.41; Z = −0.173; P = 0.863). SUVmax of the unaffected condyles was significantly lower than condylar SUVmax in the corresponding age group (3.96 ± 1.07 vs. 5.50 ± 1.41; Z = −5.833; P = 0.000). SUVmax cutoff values for identifying active condyle were 6.26 and 4.53 in patients of 13–19 and 20–29 years old, respectively.

Conclusions

The condylar SUVmax varied with age. Different cutoff values of condylar SUVmax should be employed for diagnosing active UCH for patients in different ages.
The impact of 18F-fluorodeoxyglucose PET/computed tomography on clinical staging in bladder cancer
Authors: Coskun Nazim , Cagdas Berkay , Eroglu Unsal , Aslan Yilmaz , Turkolmez Seyda
Published: November 2021

Aim

To determine the impact of 18F-FDG PET/computed tomography (CT) on clinical staging in bladder cancer with comparison to conventional CT and MRI.

Methods

A total of 142 patients who underwent 18F-FDG PET/CT imaging with a diagnosis of bladder cancer between 1 June 2019 and 31 December 2020 were screened retrospectively. Seventy patients who underwent diagnostic CT or MRI within 2 months before or after PET/CT were included in the study. The N and M stages determined by CT, MRI and PET/CT according to the eighth version of the TNM staging system were recorded. T-test was used to determine the levels of significant difference, and univariate logistic regression analysis was used to evaluate the impact of the T stage on nodal up-staging.

Results

According to the PET/CT, the N stage increased in 19 patients (27.14%) and decreased in seven patients (10%). Likewise, the M stage increased in 16 patients (22.86%) and decreased in seven patients (10%). The N stage determined by PET/CT was confirmed by pathologic examination in all cases in which the two modalities were inconsistent. In muscle-invasive cases, the rate of increase in the N stage after PET/CT (36.95%) was found to be significantly higher than in that of cases without invasion (8.33%) (P = 0.011). Increasing T stage was associated with an increase in the N stage after PET/CT (odds ratio: 2.33, 95% confidence interval: 1.02–5.28, P = 0.042).

Conclusion

18F-FDG PET/CT can potentially change the clinical stage determined by CT and MRI when used for staging in bladder cancer, and can lead to nodal up-staging particularly in cases with muscle-invasive bladder cancer.
Von Hippel–Lindau disease-associated renal cell carcinoma: a call to action
Authors: Larcher Alessandro , Rowe Isaline , Belladelli Federico , Fallara Giuseppe , Raggi Daniele , Necchi Andrea , Montorsi Francesco , Capitanio Umberto , Salonia Andrea
Published: November 2021

Purpose of review

While the molecular and genetic bases of Von Hippel–Lindau (VHL) disease have been extensively investigated, limited evidence is available to guide diagnosis, local or systemic therapy, and follow-up. The aim of the current review is to summarize the ongoing trials both in preclinical and clinical setting regarding VHL disease management.

Recent findings

Although genotype/phenotype correlations have been described, there is considerable inter and intra-familiar heterogeneity in VHL disease. Genetic anticipation has been reported in VHL disease. From a clinical point of view, expert-opinion-based protocols suggest testing those patients with any blood relative of an individual diagnosed with VHL disease, those with at least 1 or more suggestive neoplasms or patients presenting with clear cell renal cell carcinoma (ccRCC) diagnosed at a less than 40 years old, and/or multiple ccRCC. Clinical research is focused on safety and efficacy of systemic agents for patients with VHL-related ccRCC, with the aim to possibly preserve kidney function and improve patient survival.

To date, preclinical and clinical research on the topic is scarce and clinical guidelines are not supported by strong validation studies.
Development of an accessible gene expression bioinformatics pipeline to study driver mutations of colorectal cancer
Authors: van den Driest Lisa , Johnson Caroline H , Rattray Nicholas JW , Rattray Zahra
Published: November 2021

Colorectal cancer (CRC) is a global cause of cancer-related mortality driven by genetic and environmental factors which influence therapeutic outcomes. The emergence of next-generation sequencing technologies enables the rapid and extensive collection and curation of genetic data for each cancer type into clinical gene expression biobanks.

In this study we used a combination of bioinformatics tools to investigate the expression patterns and prognostic significance of two genes, adenomatous polyposis coli (APC) and B-Raf proto-oncogene (BRAF), that are commonly dysregulated in colon cancer. Subsequently, we investigated the pathways and biomolecular effectors implicated in APC and BRAF function.

Our results show mutation types, frequency, anatomical location and differential expression patterns for APC and BRAF between colorectal tumour and matched healthy tissue. The prognostic values of APC and BRAF was investigated as a function of expression level in CRC and other cancer types.

In the era of precision medicine and with significant advancements in biobanking and data curation, there is significant scope to use existing clinical datasets for evaluating the role of mutational drivers in carcinogenesis. This offers the potential for studying combinations of less well-known genes and the discovery of novel biomarkers or studying the association between various effector proteins and pathways.
Rewiring glucose metabolism improves 5-FU efficacy in glycolytic p53-deficient colorectal tumors
Authors: Ludikhuize Marlies C. , Gevers Sira , Nguyen Nguyen T.B. , Meerlo Maaike , Shafiei Roudbari S. Khadijeh , Gulersonmez M. Can , Stigter Edwin C.A. , Drost Jarno , Clevers Hans , Burgering Boudewijn M.T. , Rodríguez Colman Maria J.
Published: November 2021

5-fluorouracil (5-FU) is the backbone for chemotherapy in colorectal cancer (CRC). Response rates in patients are, however, limited to 50%. Despite the importance of 5-FU, the molecular mechanisms by which it induces toxicity remain unclear, limiting the development of strategies to improve efficacy. How fundamental aspects of cancer, such as driver mutations and phenotypic intra-tumor heterogeneity, relate to the 5-FU response is also ill-defined. This is largely due to the shortage of mechanistic studies executed in pre-clinical models that can faithfully recapitulate key CRC features. Here, we analyzed the 5-FU response in human organoids genetically engineered to reproduce the different stages of CRC progression. We find that 5-FU induces pyrimidine imbalance, which leads to DNA damage and cell death. Actively proliferating cancer (stem) cells are accordingly efficiently targeted by 5-FU. Importantly, p53 behaves as a discriminating factor for 5-FU sensitivity, whereas p53-deficiency leads to DNA damage-induced cell death, active p53 protects from these effects through inducing cell cycle arrest. Moreover, we find that targeting the Warburg effect, by rewiring glucose metabolism, enhances 5-FU toxicity by further altering the nucleotide pool and without increasing toxicity in healthy-non-transformed cells. Thus, targeting cancer metabolism in combination with replication stress-inducing chemotherapies emerges as a promising strategy for CRC treatment.
The Genomic Prehistory of the Indigenous People of Uruguay
Authors: Lindo John , De La Rosa Rosseirys , dos Santos Andre Luiz Campelo , Sans Mónica , DeGiorgio Michael , Figueiro Gonzalo
Published: November 2021

The prehistory of the people of Uruguay is greatly complicated by the dramatic and severe effects of European contact, as with most of the Americas. After the series of military campaigns that exterminated the last remnants of nomadic peoples, Uruguayan official history masked and diluted the former indigenous ethnic diversity into the narrative of a singular people that all but died out. Here we present the first whole genome sequences of the Indigenous people of the region before the arrival of Europeans, from an archaeological site in eastern Uruguay that dates from 2,000 years before present. We find a surprising connection to ancient individuals from Panama and eastern Brazil, but not to modern Amazonians. This result may be indicative of a distinct migration route into South America that may have occurred along the Atlantic coast. We also find a distinct ancestry previously undetected in South America. Though this work begins to piece together some of the demographic nuance of the region, the sequencing of ancient individuals from across Uruguay is needed to better understand the ancient prehistory and genetic diversity that existed before European contact, thereby helping to rebuild the history of the indigenous population of what is now Uruguay.
CAN A MACHINE LEARNING ALGORITHM IDENTIFY SARS-COV-2 VARIANTS BASED ON CONVENTIONAL rRT-PCR? PROOF OF CONCEPT
Authors: Cabrera Alvargonzález Jorge , Larrañaga Janeiro Ana , Pérez Castro Sonia , Martínez Torres Javier , Martínez Lamas Lucía , Daviña Nuñez Carlos , Del Campo-Pérez Víctor , Suarez Luque Silvia , García Benito Regueiro , Porteiro Fresco Jacobo
Published: November 2021

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been and remains one of the major challenges humanity has faced thus far. Over the past few months, large amounts of information have been collected that are only now beginning to be assimilated. In the present work, the existence of residual information in the massive numbers of rRT-PCRs that tested positive out of the almost half a million tests that were performed during the pandemic is investigated. This residual information is believed to be highly related to a pattern in the number of cycles that are necessary to detect positive samples as such. Thus, a database of more than 20,000 positive samples was collected, and two supervised classification algorithms (a support vector machine and a neural network) were trained to temporally locate each sample based solely and exclusively on the number of cycles determined in the rRT-PCR of each individual. Finally, the results obtained from the classification show how the appearance of each wave is coincident with the surge of each of the variants present in the region of Galicia (Spain) during the development of the SARS-CoV-2 pandemic and clearly identified with the classification algorithm.
The manipulation of spinal motor neuron axonal growth promotes spinal cord repair
Authors: Wang Feng , Fu Xin-Ya , Li Mei-Mei , Wang Xing-Ran , Xie Ji-Le , Ma Jin-Jin , Ma Yan-Xia , Saijilafu
Published: November 2021

The loss of motor function in patients with spinal cord injury (SCI) is primarily due to the severing of the corticospinal tract (CST). Spinal motor neurons are located in the anterior horn of the spinal cord, and as the lower neurons of the CST, they control voluntary movement. Furthermore, its intrinsic axonal growth ability is significantly stronger than that of cerebral cortex pyramid neurons, which are the upper CST neurons. Therefore, we established an axonal regeneration model of spinal motor neurons to investigate the feasibility of repairing SCI by promoting axonal regeneration of spinal motor neurons. We demonstrated that conditionally knocking out pten in mature spinal motor neurons drastically enhanced axonal regeneration in vivo, and the regenerating axons of the spinal motor neurons re-established synapses with other cells in the damaged spinal cord. Thus, this strategy may serve as a novel and effective treatment method for SCI.
A live attenuated influenza virus-vectored intranasal COVID-19 vaccine provides rapid, prolonged, and broad protection against SARS-CoV-2 infection
Authors: Chen Junyu , Wang Pui , Yuan Lunzhi , Zhang Liang , Zhang Limin , Zhao Hui , Chen Congjie , Chen Yaode , Han Jinle , Jia Jizong , Lu Zhen , Hong Junping , Chen Liqiang , Fan Changfa , Lu Zicen , Wang Qian , Chen Rirong , Cai Minping , Qi Ruoyao , Wang Xijing , Ma Jian , Zhou Min , Yu Huan , Zhuang Chunlan , Liu Xiaohui , Han Qiangyuan , Wang Guosong , Su Yingying , Yuan Quan , Cheng Tong , Wu Ting , Ye Xiangzhong , Li Changgui , Zhang Tianying , Zhang Jun , Zhu Huachen , Chen Yixin , Chen Honglin , Xia Ningshao
Published: November 2021

Remarkable progress has been made in developing intramuscular vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, they are limited with respect to eliciting local immunity in the respiratory tract, which is the primary infection site for SARS-CoV-2. To overcome the limitations of intramuscular vaccines, we constructed a nasal vaccine candidate based on an influenza vector by inserting a gene encoding the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2, named CA4-dNS1-nCoV-RBD (dNS1-RBD). A preclinical study showed that in hamsters challenged 1 day and 7 days after single-dose vaccination or 6 months after booster vaccination, dNS1-RBD largely mitigated lung pathology, with no loss of body weight, caused by either the prototype-like strain or beta variant of SARS-CoV-2. Lasted data showed that the animals could be well protected against beta variant challenge 9 months after vaccination. Notably, the weight loss and lung pathological changes of hamsters could still be significantly reduced when the hamster was vaccinated 24 h after challenge. Moreover, such cellular immunity is relatively unimpaired for the most concerning SARS-CoV-2 variants. The protective immune mechanism of dNS1-RBD could be attributed to the innate immune response in the nasal epithelium, local RBD-specific T cell response in the lung, and RBD-specific IgA and IgG response. Thus, this study demonstrates that the intranasally delivered dNS1-RBD vaccine candidate may offer an important addition to fight against the ongoing COVID-19 pandemic, compensating limitations of current intramuscular vaccines, particularly at the start of an outbreak.
A computational study on the optimization of transcranial temporal interfering stimulation with high-definition electrode using unsupervised neural network
Authors: Bahn Sang-kyu , Kang Bo-Yeong , Lee Chany
Published: November 2021

Transcranial temporal interfering stimulation (tTIS) can focally stimulate deep parts of the brain, which are related to specific functions, by using beats at two high AC frequencies that do not affect the human brain. However, it has limitations in terms of calculation time and precision for optimization because of its complexity and non-linearity. We aimed to propose a method using an unsupervised neural network (USNN) for tTIS to optimize quickly the interfering current value of high-definition electrodes, which can finely stimulate the deep part of the brain, and analyze the performance and characteristics of tTIS. A computational study was conducted using 16 realistic head models. This method generated the strongest stimulation on the target, even when targeting deep areas or multi-target stimulation. The tTIS was robust with target depth compared with transcranial alternating current stimulation, and mis-stimulation could be reduced compared with the case of using two-pair inferential stimulation. Optimization of a target could be performed in 3 min. By proposing the USNN for tTIS, we showed that the electrode currents of tTIS can be optimized quickly and accurately, and the possibility of stimulating the deep part of the brain precisely with transcranial electrical stimulation was confirmed.
Assessment of Airborne Disease Transmission Risk and Energy Impact of HVAC Mitigation Strategies
Authors: Risbeck Michael J. , Bazant Martin Z. , Jiang Zhanhong , Lee Young M. , Drees Kirk H. , Douglas Jonathan D.
Published: November 2021

The COVID-19 pandemic has focused renewed attention on the ways in which building HVAC systems may be operated to mitigate the risk of airborne disease transmission. The most common suggestion is to increase outdoor-air ventilation rates so as to dilute the concentrations of infectious aerosol particles indoors. Although this strategy does reduce the likelihood of disease spread, it is often much more costly than other strategies that provide equivalent particle removal or deactivation. To address this tradeoff and arrive at practical recommendations, we explain how different mitigation strategies can be expressed in terms of equivalent outdoor air (EOA) to provide a common basis for energy analysis. We then show the effects of each strategy on EOA delivery and energy cost in simulations of realistic buildings in a variety of climates. Key findings are that in-duct filtration is often the most efficient mitigation strategy, while significant risk reduction generally requires increasing total airflow to the system, either through adjusted HVAC setpoints or standalone disinfection devices.
Precise blood proteome profiling in an undiagnosed population with COVID-19
Authors: Fredolini Claudia , Dodig-Crnković Tea , Bendes Annika , Dahl Leo , Dale Matilda , Mattsson Cecilia , Thomas Cecilia E , Beck Olof , Roxhed Niclas , Schwenk Jochen M
Published: November 2021

Self-sampled blood provided valuable information about the COVID-19 seroprevalence in the general population. To enable an even deeper understanding of pathophysiological processes following SARS-CoV-2 infections, 276 circulating proteins were quantified by proximity extension assays in dried blood spots (DBS). Samples from undiagnosed individuals collected during the first wave of the pandemic were selected based on their serological immune response and matched on self-reported symptoms. We stratified these as seropositive (IgM+IgG+;N= 41) or seronegative (IgM-IgG-;N= 37), and to represent the acute (IgM+IgG-;N= 26) and convalescent phases (IgM-IgG+;N= 40). This revealed proteins from a variety of clinical processes including inflammation and immune response (MBL2, MMP3, IL2RA, FCGR2A, CCL5), haemostasis (GP1BA, VWF), stress response (ANG), virus entry (SDC4) or nerve regeneration (CHL1). The presented approach complements clinical surveys and enables a deep molecular and population-wide analysis of COVID-19 from blood specimens collected outside a hospital setting.
Copy number heterogeneity identifies ER+ breast cancer patients with adverse outcome after adjuvant endocrine therapy
Authors: van den Bosch Tom , Rueda Oscar M , Caldas Carlos , Vermeulen Louis , Miedema Daniël M
Published: November 2021

Background

Endocrine therapy forms the backbone of adjuvant treatment for estrogen-receptor positive (ER+) breast cancer. However, it remains unclear whether adjuvant treatment improves survival rates in low-risk patients. Low intra-tumor heterogeneity (ITH) has been shown to confer low-risk for recurrent disease. Here, it is studied if chromosomal copy number ITH (CNH) can identify low-risk ER+, lymph node-negative breast cancers patients who do not benefit from adjuvant endocrine therapy.

Methods

Lymph node-negative ER+ patients from the METABRIC dataset were retrospectively analyzed (n=708). CNH was determined from a single bulk copy number measurement for each patient. Patients were stratified by CNH score as low, medium or high. Overall survival (OS) was compared between patients that did, or did not receive adjuvant endocrine therapy per CNH group with Cox proportional-hazards models, using propensity score weights to correct for confounders.

Results

Adjuvant endocrine therapy improved the relapse free survival (RFS) for high-CNH/high-risk patients treatment (Hazard Ratio [HR] = 0.55, 95% Confidence Interval [CI] = 0.35 to 0.87), but not for low CNH/risk patients treatment (HR = 0.88, 95% CI = 0.50 to 1.55). For low-CNH/low-risk patients adjuvant endocrine therapy was associated with impaired OS (HR = 1.62, 95% CI = 1.10 to 2.40). Multivariable Cox analysis identified a significant interaction between CNH and endocrine therapy for OS (HR = 0.77, 95% CI = 0.62 to 0.96).

Conclusions

This retrospective study of lymph node-negative, ER+ breast cancer finds that patients identified as low-risk using CNH display reduced OS when treated with adjuvant endocrine therapy.