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S Rossi, A Orrico, C Santamaria, V Romano, L De Rosa, F Simonelli, G De RosaMultidisciplinary Department of Medical, Surgical and Dental Sciences, Eye Clinic, Second University of Naples, Naples, ItalyPurpose: Evaluating the clinical results of trans-epithelial collagen cross-linking (CXL) and standard CXL in patients with progressive keratoconus.Methods: This prospective study comprised 20 eyes of 20 patients with progressive keratoconus. Ten eyes were treated by standard CXL and ten by trans-epithelial cross-linking (TE-CXL, epithelium on) with 1 year of follow-up. All patients underwent complete ophthalmologic testing that included pre- and postoperative uncorrected visual acuity, corrected visual acuity, spherical error, spherical equivalent, corneal astigmatism, simulated maximum, minimum, and average keratometry, coma and spherical aberration, optical pachymetry, and endothelial cell density. Intra- and postoperative complications were recorded. The solution used for standard CXL comprised riboflavin 0.1% and dextran 20.0% (Ricrolin), while the solution for TE-CXL (Ricrolin, TE) comprised riboflavin 0.1%, dextran 15.0%, trometamol (Tris), and ethylenediaminetetraacetic acid. Ultraviolet-A treatment was performed with UV-X System at 3 mW/cm2.Results: In both the standard CXL group (ten patients, ten eyes; mean age, 30.4±7.3 years) and the TE-CXL group (ten patients, ten eyes; mean age, 28±3.8 years), uncorrected visual acuity and corrected visual acuity improved significantly after treatment. Furthermore, a significant improvement in topographic outcomes, spherical error, and spherical equivalent was observed in both groups at month 12 posttreatment. No significant variations were recorded in other parameters. No complications were noted.Conclusion: A 1-year follow-up showed stability of clinical and refractive outcomes after standard CXL and TE-CXL.Keywords: corneal disease, corneal thickness, keratoconus, refractive outcomes, surgical technique

The intent of this review is to present basic genetic concepts key to understanding oncogenesis and the role receptor tyrosine kinase (RTK) inhibition plays in the targeted treatment of many cancer types. Oncogenic signaling by RTKs can result from genetic events such as point mutations, chromosomal rearrangements, structural variation, and gene amplification in the cancer genome. The cancer pharmacogenes discussed encode RTKs that exemplify the link between gene variation, the oncogenic process, and the basis of targeted approaches to treatment. Biochemical pathways often involved in oncogenesis and affected by RTK variation are reviewed. Molecular diagnostic testing for the presence of specific gene variants, alterations, and amplifications direct therapy to indicated tyrosine kinase inhibitors and monoclonal antibody drugs. As pharmacists are integral to the selection, preparation, and monitoring of chemotherapy, it is important that they understand the genetic basis for targeted therapies as well as the underlying disease process.

Resumo As redes de transporte desempenham um importante papel no desenvolvimento das cidades e no acesso a oportunidades. O planejamento de transportes, contudo, ainda não reconhece seu papel na promoção de desigualdades. Este trabalho busca discutir os conceitos de centralização e acessibilidade e apresentar um paradigma de desenho de redes de transporte coletivo, baseado na compreensão de que sua demanda contém um componente endógeno: ao promover acessibilidade, os sistemas de transporte coletivo incentivam parte da demanda que buscam atender, levando a um ciclo de causação circular. Propõe-se, então, que o planejamento das redes de transporte coletivo deva estar fortemente associado à disciplina de planejamento urbano, considerando não só a demanda existente, mas o desenho de cidade que se deseja construir.

Our goal was to determine the cellular immune response (CIR) in a sample of the Borriana COVID-19 cohort (Spain) to identify associated factors and their relationship with infection, reinfection and sequelae. We conducted a nested case–control study using a randomly selected sample of 225 individuals aged 18 and older, including 36 individuals naïve to the SARS-CoV-2 infection and 189 infected patients. We employed flow-cytometry–based immunoassays for intracellular cytokine staining, using Wuhan and BA.2 antigens, and chemiluminescence microparticle immunoassay to detect SARS-CoV-2 antibodies. Logistic regression models were applied. A total of 215 (95.6%) participants exhibited T-cell response (TCR) to at least one antigen. Positive responses of CD4+ and CD8+ T cells were 89.8% and 85.3%, respectively. No difference in CIR was found between naïve and infected patients. Patients who experienced sequelae exhibited a higher CIR than those without. A positive correlation was observed between TCR and anti-spike IgG levels. Factors positively associated with the TCR included blood group A, number of SARS-CoV-2 vaccine doses received, and anti-N IgM; factors inversely related were the time elapsed since the last vaccine dose or infection, and blood group B. These findings contribute valuable insights into the nuanced immune landscape shaped by SARS-CoV-2 infection and vaccination.

The incorporation of monensin into cattle diets can significantly alter the physicochemical properties of excreted manure, potentially affecting waste management and treatment systems given the persistence of substantial concentrations of ionophores in the effluent. This study assessed the impact of monensin on the compositional characteristics of cattle manure and its implications for anaerobic digestion efficiency, with and without the separation of manure fractions across two hydraulic retention times (HRTs). Manure samples were collected from cattle fed with doses of monensin at 0, 1.8, 3.6, 5.4, and 7.2 mg per kg of dry matter intake. The HRTs investigated were 20 days (HRT20) and 30 days (HRT30). Increasing monensin inclusion in the diets resulted in a notable decrease in the quantities of total solids (TSs), volatile solids (VSs), and neutral detergent fiber (NDF) per animal per day, accompanied by an increase in lignin content and mass. Fraction separation during anaerobic digestion enhances the reduction of TSs, VSs, and NDF, thereby optimizing biogas and methane production potentials and elevating methane concentrations. The presence of monensin correlated with the reduced degradation of organic components during the anaerobic digestion process. To maximize the efficiency of the anaerobic digestion of manure from cattle diets supplemented with monensin, a 30-day HRT combined with fraction separation is recommended. This approach can enhance biogas yield and methane content, thereby improving the sustainability and efficacy of waste treatment processes.

Background: A new monoclonal antibody (nirsevimab; Beyfortus®) and a bivalent prefusion RSV vaccine (Abrysvo®) for maternal immunization have been approved recently. This is a modelling study to estimate the potential impact of different immunization programs with these products on RSV-bronchiolitis. Methods: Population-based real-world data from primary care and hospitalizations were considered. RSV bronchiolitis dynamics in absence of these immunization scenarios were explained by a multivariate age-structured Bayesian model. Then, the potential impact was simulated under different assumptions including the most recent clinical trial data. Differences in endpoints, populations, and timeframes between trials make the two products’ efficacy difficult to compare. Results: A seasonal with catch-up program, assuming a constant effectiveness of 79.5 % during the first 5 months followed by a linear decay to 0 by month 10 with nirsevimab, would prevent between 5121 and 8846 RSV bronchiolitis per 100,000 infants-years. Assuming 77.3 % effectiveness with the same decay, between 976 and 1686 RSV-hospitalizations per 100,000 infants-years could be prevented depending on the uptake. A year-round maternal immunization program, with 51 % of effectiveness during the first 6 months followed by a linear decay to 0 by month 10 would prevent between 3246 and 5606 RSV bronchiolitis cases per 100,000 infants-years. Assuming 56.9 % effectiveness with the same decay, between 713 and 1231 RSV-hospitalizations per 100,000 infants-years could be prevented. Conclusions: Our results suggest that each strategy would effectively reduce RSV-bronchiolitis.

Ocean color satellites require a procedure known as System Vicarious Calibration (SVC) after launch as the pre-launch and on-orbit calibration accuracy is insufficient. The current approach for determination of post-launch SVC uses a single fixed measurement location and may be susceptible to unexpected biases in satellite processing algorithms. Here we describe a novel SVC program which is based on a high resolution and high accuracy radiometric system integrated with an autonomous profiling float (providing a buoyancy engine, physical observations, and communication). This float + radiometer (HyperNav) system can be shipped via air, land, ocean and is deployable from small boats. This SVC program relies on multiple deployment sites with associated facilities to collect a significant amount of SVC quality data in a relatively short time. It has centralized logistics and command-and-control centers ensuring easy access to information regarding the status of each asset and to ensure floats stay within a certain ocean area. The development of the program has been associated with the launch of NASA’s PACE satellite and has been executed by academic institutions in collaboration with an industrial partner. Other approaches for a future float-based operational SVC program are discussed.

A novel ocean profiling float system for calibrating and validating satellite-based ocean color observations has been developed and tested. The float-based radiometric sampling system, herein referred to as HyperNav, is complementary to traditional moored in-situ observing systems and provides additional capability due to the relatively small platform size and high radiometric accuracy that allows for opportunistic deployments at locations during seasons and conditions that are best for ocean color observations. The purpose of this study is to optimize the deployment locations of an array of HyperNav systems to support the Plankton, Aerosol, Cloud, ocean Ecosystem (PACE) mission by performing System Vicarious Calibration (SVC) observations. Specifically, we present the development of logistical and scientific criteria for selecting suitable sites for developing an SVC network of profiling-float-based radiometric systems capable of calibrating and validating ocean color observations. As part of the analyses described in this paper, we have synthetically deployed HyperNav at potential US-based and international sites, including: north of Crete island; south-east of Bermuda island; south of Puerto Rico island; southwest of Port Hueneme, CA; west of Monterey, CA; west of Kona, HI; and south-west of Tahiti island. The synthetic analyses identified Kona, Puerto Rico, Crete, and Tahiti as promising SVC sites. All sites considered are suitable for generating a significant number of validation match-ups. Optimally deploying HyperNav systems at these sites during the PACE post-launch SVC campaign is expected to cost-effectively provide a large number of SVC match-ups to fulfill the PACE calibration requirements.

Objectives: We aimed to compare the risk of herpes zoster (HZ) in adults with and without laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods: This retrospective dynamic cohort study analyzed data from a public healthcare database in Spain between November 2020 and October 2021. The main outcome was incident cases of HZ in individuals ≥18-year-old. Relative risk (RR) of HZ in SARS-CoV-2-confirmed versus SARS-CoV-2-free individuals was estimated by a multivariable negative binomial regression adjusted by age, sex, and comorbidities. Results: Data from 4,085,590 adults were analyzed. The overall HZ incidence rate in adults was 5.76 (95% confidence interval [CI], 5.66-5.85) cases per 1000 person-years. Individuals ≥18-year-old with SARS-CoV-2-confirmed infection had a 19% higher risk of developing HZ versus SARS-CoV-2-free ≥18-year-olds (adjusted RR = 1.19; 95% CI, 1.09-1.29); this percentage was 16% (adjusted RR = 1.16; 95% CI, 1.05-1.29) in ≥50-year-olds. Severe (hospitalized) cases of SARS-CoV-2 infection had a 64% (if ≥18 years old) or 44% (if ≥50 years old) higher risk of HZ versus nonhospitalized cases. Conclusion: These results support an association between SARS-CoV-2 infection and HZ, with a greater HZ risk in severe cases of SARS-CoV-2 infection.

Hyperspectral optical observations of the Earth’s surface oceans from space offer a means to improve our understanding of ocean biology and biogeochemistry. NASA’s Plankton, Aerosol, Cloud, ocean Ecosystem (PACE) satellite mission, which includes a hyperspectral ocean color instrument (OCI), will provide radiometric observations of surface ocean with near continuous spectral resolution across the near UV to NIR range. Maintaining sufficient accuracy over the lifetime of satellite ocean color missions requires a robust program for system vicarious calibration (SVC) and product validation. The system vicarious calibration process combines satellite sensor data with in-situ radiometric/optical measurements to remove potential biases due to the combined errors from both satellite radiometric sensor calibration and atmospheric correction. As such, high accuracy, high-spectral resolution in-situ radiometric measurements are required to provide a principal source of truth for the satellite-derived products. To meet the requirements, a novel in-situ radiometric system, called HyperNav, has been developed, rigorously characterized and field tested. Key attributes of HyperNav are dual upwelling radiance heads coupled to individual spectrometers, spectral resolution of ∼2.2 nm (full width, half-maximum) across 320–900 nm, integrated shutter systems for dark measurements, and integrated tilt and pressure sensors. The HyperNav operational modes include traditional profiling and surface modes, as well as integration with an autonomous profiling float for unattended deployment, offering a new capability for a network of autonomous platforms to support the long-term needs for hyperspectral ocean color remote sensing observations. This paper describes the HyperNav design, in-situ operational modes, and field verification results.

BackgroundThe Centers for Medicare and Medicaid Services (CMS) hierarchical condition category (HCC) coding is a risk adjustment model that allows for the estimation of risk-and cost-associated with health care provision. Current models may not include key factors that fully delineate the risk associated with spine surgery.ObjectiveTo augment CMS HCC risk adjustment methodology with socioeconomic data to improve its predictive capabilities for spine surgery.MethodsThe National Inpatient Sample was queried for spinal fusion, and the data was merged with county-level coverage and socioeconomic status variables obtained from the Brookings Institute. We predicted outcomes (death, nonroutine discharge, length of stay [LOS], total charges, and perioperative complication) with pairs of hierarchical, mixed effects logistic regression models-one using CMS HCC score alone and another augmenting CMS HCC scores with demographic and socioeconomic status variables. Models were compared using receiver operating characteristic curves. Variable importance was assessed in conjunction with Wald testing for model optimization.ResultsWe analyzed 653 815 patients. Expanded models outperformed models using CMS HCC score alone for mortality, nonroutine discharge, LOS, total charges, and complications. For expanded models, variable importance analyses demonstrated that CMS HCC score was of chief importance for models of mortality, LOS, total charges, and complications. For the model of nonroutine discharge, age was the most important variable. For the model of total charges, unemployment rate was nearly as important as CMS HCC score.ConclusionThe addition of key demographic and socioeconomic characteristics substantially improves the CMS HCC risk-adjustment models when modeling spinal fusion outcomes. This finding may have important implications for payers, hospitals, and policymakers.

Monensin and essential oils have antimicrobial properties that may impact silage fermentation. The present study was divided into two trials to evaluate the effects of monensin (MON) and essential limonene oils (ELO) as additives in the ensiling of total mixed ration (TMR). In the first assay, TMR was tested with sheep in growth (65% dry matter—DM) using the following treatments: control (no additive), MON35 (35 mg of monensina per kg of DM), MON45 (45 mg of monensina per kg of DM), ELO300 (300 mg of essential limonene oil per kg of DM), and ELO600 (600 mg of essential limonene oil per kg of DM). In the second assay, the same treatments were used in TMR for lactating cows under two moisture conditions (30% and 40% DM). The parameters assessed included fermentative losses, short-chain fatty acid profiles, aerobic stability (hours needed for silage to reach 2 °C above ambient), chemical composition, and in vitro DM digestibility of the silages. Treatment averages were compared using the Scott–Knott test at 5% significance. In the first assay, the treatments with ELO had the lowest (p < 0.05) pH values and the highest (p < 0.05) lactic acid concentrations, with treatment ELO600 leading to the highest (p < 0.05) aerobic stability (297.88 h). Only the starch contents of the ELO treatments were lower (p < 0.05) than the others. In the second assay, the silages with the highest moisture contents and ELO600 exhibited the lowest (p < 0.05) values of DM recovery, lactic acid, and pH. The highest (p < 0.05) lactic acid:acetic acid ratios were observed in the silages with the most moisture added with MON35 and MON45. The use of MON and ELO increased aerobic stability, with the highest (p < 0.05) values observed for ELO600 and MON35. The treatments with MON and ELO resulted in silages with the lowest (p < 0.05) fiber contents and highest ether extract and starch contents when compared with control. Thus, MON and essential oils improve fermentative quality but ELO should be used in lower doses in humid silages to avoid negative fermentation impacts.

Abstract Selective serotonin reuptake inhibitors (SSRI) are common first-line treatments for major depression. However, a significant number of depressed patients do not respond adequately to these pharmacological treatments. In the present preclinical study, we demonstrate that organic cation transporter 2 (OCT2), an atypical monoamine transporter, contributes to the effects of SSRI by regulating the routing of the essential amino acid tryptophan to the brain. Contrarily to wild-type mice, OCT2-invalidated mice failed to respond to prolonged fluoxetine treatment in a chronic depression model induced by corticosterone exposure recapitulating core symptoms of depression, i.e., anhedonia, social withdrawal, anxiety, and memory impairment. After corticosterone and fluoxetine treatment, the levels of tryptophan and its metabolites serotonin and kynurenine were decreased in the brain of OCT2 mutant mice compared to wild-type mice and reciprocally tryptophan and kynurenine levels were increased in mutants’ plasma. OCT2 was detected by immunofluorescence in several structures at the blood-cerebrospinal fluid (CSF) or brain-CSF interface. Tryptophan supplementation during fluoxetine treatment increased brain concentrations of tryptophan and, more discreetly, of 5-HT in wild-type and OCT2 mutant mice. Importantly, tryptophan supplementation improved the sensitivity to fluoxetine treatment of OCT2 mutant mice, impacting chiefly anhedonia and short-term memory. Western blot analysis showed that glycogen synthase kinase-3β (GSK3β) and mammalian/mechanistic target of rapamycin (mTOR) intracellular signaling was impaired in OCT2 mutant mice brain after corticosterone and fluoxetine treatment and, conversely, tryptophan supplementation recruited selectively the mTOR protein complex 2. This study provides the first evidence of the physiological relevance of OCT2-mediated tryptophan transport, and its biological consequences on serotonin homeostasis in the brain and SSRI efficacy.

Checking the radiometric calibration of satellite hyper-spectral sensors such as the PACE Ocean Color Instrument (OCI) while they operate in orbit and evaluating remote sensing reflectance, the basic variable from which a variety of optical and biogeochemical ocean properties can be derived, requires measuring upwelling radiance just above the surface (Lw) and downwelling planar irradiance reaching the surface (Es). For this, the current HyperNav systems measure Lw at about 2 nm spectral resolution in the ultraviolet to near infrared, but Es in only four 10 nm wide spectral bands centered on 412, 489, 555, and 705 nm. In this study, the Es data acquired in these spectral bands in clear sky conditions are used to reconstruct via a multi-linear regression model the hyper-spectral Es signal at 0.5 nm resolution from 315 to 900 nm, the OCI spectral range, allowing an estimate of Es at the HyperNav, OCI, and other sensors’ resolutions. After correction of gaseous absorption and normalization by the top-of-atmosphere incident solar flux, the atmospheric diffuse transmittance is expressed as a linear combination of Es measured in those 4 spectral bands. Based on simulations for Sun zenith angles from 0 to 75° and a wide range of (i.e., expected) atmospheric, surface, and water conditions, the Es spectrum is reconstructed with a bias of less than 0.4% in magnitude and an RMS error (RMSE) ranging from 0% to 2.5%, depending on wavelength. The largest errors occur in spectral regions with strong gaseous absorption. In the presence of typical noise on Es measurements and uncertainties on the ancillary variables, the bias and RMSE become −2.5% and 7.0%, respectively. Using a General Additive Model with coefficients depending on Sun zenith angle and aerosol optical thickness at 550 nm improves statistical performance in the absence of noise, especially in the ultraviolet, but provides similar performance on noisy data, indicating more sensitivity to noise. Adding spectral bands in the ultraviolet, e.g., centered on 325, 340, and 380 nm, yields marginally more accurate results in the ultraviolet, due to uncertainties in the gaseous transmittance. Comparisons between the measured and reconstructed Es spectra acquired by the MOBY spectroradiometer show agreement within predicted uncertainties, i.e., biases less than 2% in magnitude and RMS differences less than 5%. Reconstruction can also be achieved accurately with other sets of spectral bands and extended to cloudy conditions since cloud optical properties, like aerosol properties, tend to vary regularly with wavelength. These results indicate that it is sufficient, for many scientific applications involving hyper-spectral Es, to measure Es in a few coarse spectral bands in the ultraviolet to near infrared and reconstruct the hyperspectral signal using the proposed multivariate linear modeling.

The rehabilitation of those who have undergone anterior cruciate ligament reconstruction (ACL-R) is a complex process that involves many factors. Physical ability recovery is not the only factor in the return to sport; psychosocial factors such as anxiety, pain response, self-esteem, locus of control, and fear of re-injury also play an important role. A systematic search was conducted on the PubMed, Medline, Cochrane, CINAHL and Embase databases using the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). No randomized controlled trials (RCTs) were identified. The Methodological Index for Non-Randomized Studies (MINOR) was used to assess the quality of the identified non-RCT studies. A total of 308 studies were identified, of which 32 met the eligibility criteria. The results of these studies were obtained using the KOOS (ADL, Sport, QoL), ACL, TSK-11, K-SES, questionnaires/interviews, and other scales as instrumental approaches. This systematic review and meta-analysis revealed that psychological factors have a significant influence on the post-anterior cruciate ligament reconstruction outcomes of athletes. Fear of re-injury and pain were the primary factors that limited return to sport, whereas self-efficacy, psychological will, and age were associated with better functional outcomes and were essential for male and young patients. Clinicians should focus on both physical and psychological components to optimize rehabilitation.

Annual conferences, educational courses, and other meetings draw a diverse community of individuals, yet also create a unique environment without the traditional guard rails. Unlike events held at one's home institution, clear rules and jurisdiction have not been universally established. To promote the open exchange of ideas, as well as an environment conducive to professional growth of all participants, the leading neurosurgical professional organizations joined forces to delineate the expectations for anyone who participates in sponsored events. The One Neurosurgery Summit Taskforce on Professionalism and Harassment developed a foundational policy that establishes common expectations for behavior and a unified roadmap for the prompt response to untoward events. We hope that publishing this policy will inspire other medical organizations to establish their own meeting and conference policies. More importantly, we wish to bring greater attention to everyone's responsibility for ensuring a safe and respectful space for education, scientific debate, and networking during organized events.

The first report of African swine fever virus (ASFV) genotype II in Italy in 2022 marked the beginning of a significant invasion in at least eight Italian regions with different infection clusters. In this study, we used the multi-gene approach to investigate the epidemiological associations between ASFV strains causing cases and outbreaks in wild boar and pigs in Italy from January 2022 to the end of 2023. Our results confirm that all the tested ASFV-positive Italian samples belonged to genotype II and show high homology with genotype II ASFV sequences previously collected in Eurasian countries. Molecular characterization revealed the presence of four genetic groups in Italy. The majority of African swine fever (ASF) samples analyzed in the current study (72%) belonged to genetic group 3, which was the most representative in Europe. The results also provide evidence of the prevalence of genetic group 19 (15.9%). In addition, we identified new putative genetic groups, genetic group 25 (9.1%) and genetic group 26 (3.0%), which have never been described before. This is the first detailed report on the molecular characterization of more than 130 ASFV strains circulating in Italy.

Despite the ending of social distancing and post-pandemic return to normal activities, the impacts of COVID-19 on urban mobility persist, particularly with regard to public transport. Consequently, this study looks into the post-pandemic changes in travel patterns, seeking to comprehend the effects on the municipalities and suggest helpful measures geared to achieving more sustainable patterns following the lockdown isolation. The chosen case study is the Metropolitan Area of Rio de Janeiro, Brazil. The study was divided into four distinct phases, namely understanding the problems, choosing the study area, field research and making recommendations based not only on the literature but on consultation with operators and experts. The methodological process involves the analysis of data from the field research, to assess any changes in patterns that may have been identified. The results show the changes in the means of travel, with emphasis on a preference for app-based transport services, to the detriment of sustainable transport. The study also shows the challenges facing public transport and the relationship between the choice of travel means and the socioeconomic profile of the passenger.

Public funding of vaccines may enhance vaccination rates, co-administration, and timeliness. The impacts of including the serogroup B meningococcus vaccine (MenB) into the national immunisation schedule on vaccination rates, co-administration rates, and timeliness were assessed using a population-based pre-funding (2022) and post-funding (2023) study design. MenB vaccination rates improved after funding and were in line with previously funded vaccines. Co-administration rates also increased significantly. Timely administration increased, protecting children at an early age. Public funding has a positive impact on vaccine accessibility and early protection. Consistent population characteristics highlight the role of funding.

Abstract Background Validation of a novel gene expression signature in independent data sets is a critical step in the development of a clinically useful test for cancer patient risk-stratification. However, validation is often unconvincing because the size of the test set is typically small. To overcome this problem we used publicly available breast cancer gene expression data sets and a novel approach to data fusion, in order to validate a new breast tumor intrinsic list. Results A 105-tumor training set containing 26 sample pairs was used to derive a new breast tumor intrinsic gene list. This intrinsic list contained 1300 genes and a proliferation signature that was not present in previous breast intrinsic gene sets. We tested this list as a survival predictor on a data set of 311 tumors compiled from three independent microarray studies that were fused into a single data set using Distance Weighted Discrimination. When the new intrinsic gene set was used to hierarchically cluster this combined test set, tumors were grouped into LumA, LumB, Basal-like, HER2+/ER-, and Normal Breast-like tumor subtypes that we demonstrated in previous datasets. These subtypes were associated with significant differences in Relapse-Free and Overall Survival. Multivariate Cox analysis of the combined test set showed that the intrinsic subtype classifications added significant prognostic information that was independent of standard clinical predictors. From the combined test set, we developed an objective and unchanging classifier based upon five intrinsic subtype mean expression profiles (i.e. centroids), which is designed for single sample predictions (SSP). The SSP approach was applied to two additional independent data sets and consistently predicted survival in both systemically treated and untreated patient groups. Conclusion This study validates the "breast tumor intrinsic" subtype classification as an objective means of tumor classification that should be translated into a clinical assay for further retrospective and prospective validation. In addition, our method of combining existing data sets can be used to robustly validate the potential clinical value of any new gene expression profile.

Our objective was to estimate the incidence of COVID-19 and the ABO blood Groups in the mass-gathering events (MGEs) during the Falles Festival in Borriana (Spain) from 6–10 March 2020. We conducted a population-based retrospective cohort study and measured anti-SARS-CoV-2 antibodies and the ABO of participants. We performed laboratory COVID-19 tests and obtained the ABO in 775 subjects (72.8% of the original exposed cohort): O-group (45.2%), A-group (43.1%), B-group (8.5%) and AB-group (3.4%). Adjusted for confounding factors, including COVID-19 exposure during the MGEs, attack rates of COVID-19 for each ABO group were 55.4%, 59.6%, 60.2%, and 63.7%. The adjusted relative risks were for O-group 0.93 (95% Confidence Interval [CI] 0.83–1.04), for A-group 1.06 (95% CI 0.94–1.18), for B-group 1.04 (95%CI 0.88–1.24), and for AB-group 1.11 (95% CI 0.81–1.51) with no significant differences. Conclusions: Our results suggest no effect of ABO on COVID-19 incidence. We observed weak but not significant protection of the O-group and not a significantly greater infection risk for the remaining groups compared with the O-group. More studies are needed to resolve the controversies regarding the association between ABO and COVID-19.