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Richard Houlston and colleagues report results of a genome-wide association study of chronic lymphocytic leukemia. They validate several new susceptibility loci for this disease, including variants near POT1 , TERC and TERT . Genome-wide association studies (GWAS) of chronic lymphocytic leukemia (CLL) have shown that common genetic variation contributes to the heritable risk of CLL. To identify additional CLL susceptibility loci, we conducted a GWAS and performed a meta-analysis with a published GWAS totaling 1,739 individuals with CLL (cases) and 5,199 controls with validation in an additional 1,144 cases and 3,151 controls. A combined analysis identified new susceptibility loci mapping to 3q26.2 (rs10936599, P = 1.74 × 10 −9 ), 4q26 (rs6858698, P = 3.07 × 10 −9 ), 6q25.2 ( IPCEF1 , rs2236256, P = 1.50 × 10 −10 ) and 7q31.33 ( POT1 , rs17246404, P = 3.40 × 10 −8 ). Additionally, we identified a promising association at 5p15.33 ( CLPTM1L , rs31490, P = 1.72 × 10 −7 ) and validated recently reported putative associations at 5p15.33 ( TERT , rs10069690, P = 1.12 × 10 −10 ) and 8q22.3 (rs2511714, P = 2.90 × 10 −9 ). These findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to CLL.

Richard Houlston and colleagues identify common variants at four loci associated with risk of chronic lymphocytic leukemia, including a coding variant in FARP2 on 2q37.3 and a noncoding variant in the region upstream of MYC on 8q24.21. To identify new risk variants for chronic lymphocytic leukemia (CLL), we conducted a genome-wide association study of 299,983 tagging SNPs, with validation in four additional series totaling 2,503 cases and 5,789 controls. We identified four new risk loci for CLL at 2q37.3 (rs757978, FARP2 ; odds ratio (OR) = 1.39; P = 2.11 × 10 −9 ), 8q24.21 (rs2456449; OR = 1.26; P = 7.84 × 10 −10 ), 15q21.3 (rs7169431; OR = 1.36; P = 4.74 × 10 −7 ) and 16q24.1 (rs305061; OR = 1.22; P = 3.60 × 10 −7 ). We also found evidence for risk loci at 15q25.2 (rs783540, CPEB1 ; OR = 1.18; P = 3.67 × 10 −6 ) and 18q21.1 (rs1036935; OR = 1.22; P = 2.28 × 10 −6 ). These data provide further evidence for genetic susceptibility to this B-cell hematological malignancy.

Richard Houlston and colleagues identify four new susceptibility loci for colorectal cancer through a meta-analysis of genome-wide association data, followed by replication testing in a large collection of independent samples. The study brings to ten the number of confirmed loci harboring low-penetrance risk alleles for this common malignancy. Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly influence the risk of developing colorectal cancer (CRC). To enhance power to identify additional loci with similar effect sizes, we conducted a meta-analysis of two GWA studies, comprising 13,315 individuals genotyped for 38,710 common tagging SNPs. We undertook replication testing in up to eight independent case-control series comprising 27,418 subjects. We identified four previously unreported CRC risk loci at 14q22.2 (rs4444235, BMP4 ; P = 8.1 × 10 −10 ), 16q22.1 (rs9929218, CDH1 ; P = 1.2 × 10 −8 ), 19q13.1 (rs10411210, RHPN2 ; P = 4.6 × 10 −9 ) and 20p12.3 (rs961253; P = 2.0 × 10 −10 ). These findings underscore the value of large sample series for discovery and follow-up of genetic variants contributing to the etiology of CRC.

Richard Houlston and colleagues identify variants at six loci associated with risk of chronic lymphocytic leukemia. These findings confirm that common, low-penetrance susceptibility alleles contribute to this hematological malignancy and provide new insights into disease etiology. We conducted a genome-wide association study of 299,983 tagging SNPs for chronic lymphocytic leukemia (CLL) and performed validation in two additional series totaling 1,529 cases and 3,115 controls. We identified six previously unreported CLL risk loci at 2q13 (rs17483466; P = 2.36 × 10 −10 ), 2q37.1 (rs13397985, SP140 ; P = 5.40 × 10 −10 ), 6p25.3 (rs872071, IRF4 ; P = 1.91 × 10 −20 ), 11q24.1 (rs735665; P = 3.78 × 10 −12 ), 15q23 (rs7176508; P = 4.54 × 10 −12 ) and 19q13.32 (rs11083846, PRKD2; P = 3.96 × 10 −9 ). These data provide the first evidence for the existence of common, low-penetrance susceptibility to a hematological malignancy and new insights into disease causation in CLL.

67 213 1.94 (1.40-2.66) 100 113 1.52 (1.12-2.07) 1.71 (1.37-2.13) 0.28 (13.7%)

Streptococcus equi subsp. zooepidemicus (SEZ) is a major problem in equine veterinary medicine. Typically, a commensal in horses, SEZ can cause severe disease including respiratory infections, septicaemia and reproductive tract infections under certain conditions. Recent evidence suggests that humans can also develop severe disease infection through direct contact with infected animals or the consumption of contaminated unpasteurised milk and milk products. This study investigates SEZ strains isolated from nasal swabs of equidae in central Italy in 2023 to describe the epidemiology and genomic characteristics of circulating strains. A sampling plan was implemented to randomly collect nasal swabs from equid farms in the Abruzzo and Molise regions. In addition, a sampling form was designed to collect information on risk factors related to the presence of the bacterium and the potential development of respiratory disease. Relative risk was used to measure the association between the presence of SEZ in the samples and various variables. The swabs were analysed by real-time PCR and isolation. To confirm the identification and characterise the strains, the isolates were fully sequenced by next-generation sequencing (NGS) using the Illumina platform. A total of 478 animals from 99 farms were sampled and 30% of the animals tested positive for SEZ (79% horses, 20% donkeys, 1% mules). Forty-five percent of the farms tested positive for SEZ. Monitoring the clonal spread of SEZ is essential to understand the ecology of this emerging zoonotic pathogen, to assess the risk, and to implement effective control measures. In addition, genomic assessments are recommended to investigate the pathogenicity of circulating strains. This study provides a comprehensive understanding of the epidemiology and genomic diversity of SEZ strains isolated in central Italy.

In light of the emerging breakthroughs in cancer biology, drug discovery, and personalized medicine, Tumor-on-Chip (ToC) platforms have become pivotal tools in current biomedical research. This study introduced a novel rapid prototyping approach for the fabrication of a ToC device using laser-patterned poly(methyl methacrylate) (PMMA) layers integrated with a polylactic acid (PLA) electrospun scaffold, enabling dynamic drug delivery and the assessment of therapeutic efficacy in cancer cells. Traditional drug screening methods, such as conventional cell cultures, mimic certain aspects of cancer progression but fail to capture critical features of the tumor microenvironment (TME). While animal models offer a closer approximation of tumor complexity, they are limited in their ability to predict human drug responses. Here, we evaluated the ability of our ToC device to recapitulate the interactions between cancer and TME cells and its efficacy in evaluating the drug response of breast cancer cells. The functional design of the proposed ToC system offered substantial potential for a wide range of applications in cancer research, significantly accelerating the preclinical assessment of new therapeutic agents.

To date, four vaccines have been authorised for emergency use and under conditional approval by the European Medicines Agency to prevent COVID-19: Comirnaty, COVID-19 Vaccine Janssen, Spikevax (previously COVID-19 Vaccine Moderna) and Vaxzevria (previously COVID-19 Vaccine AstraZeneca). Although the benefit–risk profile of these vaccines was proven to be largely favourable in the general population, evidence in special cohorts initially excluded from the pivotal trials, such as pregnant and breastfeeding women, children/adolescents, immunocompromised people and persons with a history of allergy or previous SARS-CoV-2 infection, is still limited. In this narrative review, we critically overview pre- and post-marketing evidence on the potential benefits and risks of marketed COVID-19 vaccines in the above-mentioned special cohorts. In addition, we summarise the recommendations of the scientific societies and regulatory agencies about COVID-19 primary prevention in the same vaccinee categories.

The ever-increasing prominence of the internet and digital technology in our society requires a deeper examination of how these developments alter perception of our bodies and emotions. One such consequence is the emergence of Problematic Use of the Internet (PUI) - an array of compulsive or addictive behaviors mediated by the web that detrimentally affect an individual's functioning. This suggests that some people may be shifting their consciousness from the physical realm to the digital world. The objective of this study was to investigate how shortcomings in interoception (the sensibility to bodily signals) and alexithymia (an inability to identify and express emotions) might contribute to PUI. The Internet Addiction Test (IAT), the Toronto Alexithymia Scale (TAS-20), and the Multidimensional Assessment of Interoceptive Awareness (MAIA) were used to assess a sample of 1076 adolescents and young adults aged between 16 and 26 years via an online survey. Data analysis was based on t-test, correlations and multivariate regression. 26.8% (n = 288) of participants met the criteria for moderate PUI. Individuals with PUI displayed higher levels of alexithymia (p < 0.001) and diminished abilities in certain aspects of interoceptive sensibility, including placing trust in their own bodily signals (p = 0.006), not responding excessively to uncomfortable sensations with worry (p < 0.001), and not denying them (p = 0.006). Multivariate modelling revealed associations between PUI and the following factors: having a boyfriend/girlfriend (aOR = 5.70), substance use (aOR = 1.78), difficulty in identifying feelings (aOR = 1.09), externally oriented thinking (aOR = 1.05), low disposition in perceiving body sensations (aOR = 0.25), tendency to become distracted (aOR = 0.82) or excessively worried (aOR = 0.11) in the face of pain. Furthermore, the analysis indicated how these aspects of body perception may be interrelated, either enhancing or reducing the risk of PUI when examined individually, collectively, or in combination. This study underlines the potential connection between difficulties in the mind-body interaction and the development of PUI. It suggests a bidirectional relationship between excessive digital device use and distorted bodily interoceptive processes in PUI, reinforcing the notion that individuals struggling with emotion identification and expression may be more prone to excessive internet usage. To further comprehend the relevance of these constructs in PUI, it is necessary to conduct more targeted investigations and longitudinal studies. •The role of interoceptive sensibility and alexithymia in PUI is still unclear.•Interoceptive difficulties and alexithymia reflect a wider mind-body disconnection.•Individuals with PUI struggle engaging with their bodies and emotional experiences.•Those with emotion identification difficulties may turn to the internet for coping.•The “Digitalized Self” concept may reshape our core body and emotion experiences.

Quantification of oxidative stress is a challenging task that can help in monitoring chronic inflammatory respiratory airway diseases. Different studies can be found in the literature regarding the development of electrochemical sensors for H2O2 in cell culture medium to quantify oxidative stress. However, there are very limited data regarding the impact of the cell culture medium on the electrochemical quantification of H2O2. In this work, we studied the effect of different media (RPMI, MEM, DMEM, Ham’s F12 and BEGM/DMEM) on the electrochemical quantification of H2O2. The used electrode is based on reduced graphene oxide (rGO) and gold nanoparticles (AuNPs) and was obtained by co-electrodeposition. To reduce the electrode fouling by the medium, the effect of dilution was investigated using diluted (50% v/v in PBS) and undiluted media. With the same aim, two electrochemical techniques were employed, chronoamperometry (CH) and linear scan voltammetry (LSV). The influence of different interfering species and the effect of the operating temperature of 37 °C were also studied in order to simulate the operation of the sensor in the culture plate. The LSV technique made the sensor adaptable to undiluted media because the test time is short, compared with the CH technique, reducing the electrode fouling. The long-term stability of the sensors was also evaluated by testing different storage conditions. By storing the electrode at 4 °C, the sensor performance was not reduced for up to 21 days. The sensors were validated measuring H2O2 released by two different human bronchial epithelial cell lines (A549, 16HBE) and human primary bronchial epithelial cells (PBEC) grown in RPMI, MEM and BEGM/DMEM media. To confirm the results obtained with the sensor, the release of reactive oxygen species was also evaluated with a standard flow cytometry technique. The results obtained with the two techniques were very similar. Thus, the LSV technique permits using the proposed sensor for an effective oxidative stress quantification in different culture media and without dilution.