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Abstract Background The cancer transcriptome is difficult to explore due to the heterogeneity of quantitative and qualitative changes in gene expression linked to the disease status. An increasing number of "unconventional" transcripts, such as novel isoforms, non-coding RNAs, somatic gene fusions and deletions have been associated with the tumoral state. Massively parallel sequencing techniques provide a framework for exploring the transcriptional complexity inherent to cancer with a limited laboratory and financial effort. We developed a deep sequencing and bioinformatics analysis protocol to investigate the molecular composition of a breast cancer poly(A)+ transcriptome. This method utilizes a cDNA library normalization step to diminish the representation of highly expressed transcripts and biology-oriented bioinformatic analyses to facilitate detection of rare and novel transcripts. Results We analyzed over 132,000 Roche 454 high-confidence deep sequencing reads from a primary human lobular breast cancer tissue specimen, and detected a range of unusual transcriptional events that were subsequently validated by RT-PCR in additional eight primary human breast cancer samples. We identified and validated one deletion, two novel ncRNAs (one intergenic and one intragenic), ten previously unknown or rare transcript isoforms and a novel gene fusion specific to a single primary tissue sample. We also explored the non-protein-coding portion of the breast cancer transcriptome, identifying thousands of novel non-coding transcripts and more than three hundred reads corresponding to the non-coding RNA MALAT1, which is highly expressed in many human carcinomas. Conclusion Our results demonstrate that combining 454 deep sequencing with a normalization step and careful bioinformatic analysis facilitates the discovery and quantification of rare transcripts or ncRNAs, and can be used as a qualitative tool to characterize transcriptome complexity, revealing many hitherto unknown transcripts, splice isoforms, gene fusion events and ncRNAs, even at a relatively low sequence sampling.

Abstract Background Although the overlap of transcriptional units occurs frequently in eukaryotic genomes, its evolutionary and biological significance remains largely unclear. Here we report a comparative analysis of overlaps between genes coding for well-annotated proteins in five metazoan genomes (human, mouse, zebrafish, fruit fly and worm). Results For all analyzed species the observed number of overlapping genes is always lower than expected assuming functional neutrality, suggesting that gene overlap is negatively selected. The comparison to the random distribution also shows that retained overlaps do not exhibit random features: antiparallel overlaps are significantly enriched, while overlaps lying on the same strand and those involving coding sequences are highly underrepresented. We confirm that overlap is mostly species-specific and provide evidence that it frequently originates through the acquisition of terminal, non-coding exons. Finally, we show that overlapping genes tend to be significantly co-expressed in a breast cancer cDNA library obtained by 454 deep sequencing, and that different overlap types display different patterns of reciprocal expression. Conclusion Our data suggest that overlap between protein-coding genes is selected against in Metazoa. However, when retained it may be used as a species-specific mechanism for the reciprocal regulation of neighboring genes. The tendency of overlaps to involve non-coding regions of the genes leads to the speculation that the advantages achieved by an overlapping arrangement may be optimized by evolving regulatory non-coding transcripts.

Fibrillary aggregation of α-synuclein in Lewy body inclusions and nigrostriatal dopaminergic neuron degeneration define Parkinson's disease neuropathology. Mutations in GBA1, encoding glucocerebrosidase, are the most frequent genetic risk factor for Parkinson's disease. However, the lack of reliable experimental models able to reproduce key neuropathological signatures has hampered the clarification of the link between mutant glucocerebrosidase and Parkinson's disease pathology. Here, we describe an innovative protocol for the generation of human induced pluripotent stem cell-derived midbrain organoids containing dopaminergic neurons with nigral identity that reproduce characteristics of advanced maturation. When applied to patients with GBA1-related Parkinson's disease, this method enabled the differentiation of midbrain organoids recapitulating dopaminergic neuron loss and fundamental features of Lewy body pathology observed in human brains, including the generation of α-synuclein fibrillary aggregates with seeding activity that also propagate pathology in healthy control organoids. Still, we observed that the retention of mutant glucocerebrosidase in the endoplasmic reticulum and increased levels of its substrate glucosylceramide are determinants of α-synuclein aggregation into Lewy body-like inclusions. Consistently, the reduction of glucocerebrosidase activity accelerated α-synuclein pathology by promoting fibrillary α-synuclein deposition. Finally, we demonstrated the efficacy of ambroxol and GZ667161 - two modulators of the glucocerebrosidase pathway in clinical development for the treatment of GBA1-related Parkinson's disease - in reducing α-synuclein pathology in this model, supporting the use of midbrain organoids as a relevant pre-clinical platform for investigational drug screening., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: In May 2023, Romagna, Italy, faced a devastating flood resulting in 16 fatalities, forced displacement of 26,000 citizens, and significant economic losses. Due to potential water contamination, implementing public health strategies became imperative for the Local Health Authority to mitigate the health consequences, analyze the flood's impact on the local population's health, and detect early anomalies requiring timely public health interventions., Methods: Between June and July 2023, general practitioners who were part of the RespiVirNet surveillance network completed weekly structured forms. These forms collected data on individuals exposed or not to floodwaters and clinical syndromes. Rates per 1000 resident population aged > 14 were stratified by district, week of observation, and symptomatology. Missing data were addressed by imputation using second-order autoregressive modeling., Results: An incidence of 3.52 syndromes potentially related to flood water exposure per 1000 individuals (95% CI 2.82-4.35) was estimated. Ravenna, the city most affected by the flood, recorded the highest rate (6.05 per 1000, 95% CI 4.59-7.82). Incidence decreased in the weeks post-event. Anxiety, or trauma and stress symptoms, exhibited higher rates among the exposed, diminishing over weeks. The incidence for the non-exposed (12.76 per 1000, 95% CI 10.55-15.29) showed no significant territorial differences compared to the exposed ones., Conclusions: Syndromic surveillance provided timely information on the flood's health impact, revealing a higher incidence of individual syndromes among the non-exposed. This study contributes to guiding the implementation of future public health preparedness and response strategies for populations facing similar natural disasters.

Background: Herpes Zoster is an age dependent disease and as such it represents a problem in the Italian social context, where the demographic curve is characterized by an overrepresentation of the elderly population. Vaccines against Herpes Zoster are available, safe and effective, however coverage remains sub-optimal. This study was therefore conducted to examine the variations in Herpes Zoster vaccine uptake and confidence across different regions in Italy., Methods: This study utilized a cross-sectional computer-assisted web interview (CAWI) methodology. The survey was conducted by Dynata, an online panel provider, and involved 10,000 respondents recruited in Italy between April 11 and May 29, 2022. The sample was stratified based on geographic region, gender, and age group. Data management adhered to European Union data protection regulations, and the survey covered demographics, living conditions, and vaccination against herpes zoster (HZ), following the BeSD framework., Results: The findings indicate regional disparities in herpes zoster vaccine uptake across Italy. Notably, the Islands region exhibits a particularly low vaccination rate (2.9%), highlighting the need for targeted interventions. The multivariate regression analysis showed that sociodemographic factors, limited access to healthcare services, and inadequate awareness of vaccine eligibility contribute to the lower uptake observed in this region., Conclusion: In conclusion, this research emphasizes regional disparities in herpes zoster (HZ) vaccination uptake in Italy. Demographic, socioeconomic, and geographic factors impact individuals' willingness to receive the vaccine. The study highlights the importance of awareness of vaccine eligibility and accessible vaccination facilities in increasing uptake rates., (© 2024. The Author(s).)

Introduction: The World Health Organization defines rotavirus as among the most severe causes of viral gastroenteritis affecting children under 5 year old. Italy and other European countries do not release disaggregated data on rotavirus vaccination coverage. This study aimed to assess the uptake and drivers of rotavirus vaccination in Italy., Methods: We administered a survey to 10,000 Italian citizens recruited via an online panel and proportionate to key demographic strata. We examined rotavirus vaccine uptake among parents whose youngest child was aged 6 weeks to 4 years, their sociodemographic characteristics, their beliefs about vaccine administration, and who recommended the rotavirus vaccination., Results: A total of 711 respondents met the inclusion criteria for the rotavirus vaccine questionnaire. The uptake was estimated at 60.3% nationwide (66.4% among mothers and 50.2% among fathers). Being a mother and living in cities/suburbs was significantly associated with a higher likelihood of vaccine uptake, while fathers were more likely to be uncertain of their children's vaccine status. Living in Central Italy and having friends/relatives opposed to vaccination were found to be significantly associated with a lower likelihood of vaccine uptake, while parents' education level and children's demographics were not found to correlate with any outcomes. In 90.3% of cases, the rotavirus vaccination was recalled as being recommended by a paediatrician., Conclusions: Consistent collection of behavioural preferences and socioeconomic characteristics of recipients of rotavirus vaccine campaigns, their epidemiological information, cost-benefit, and national policy data are crucial for designing effective vaccination strategies in Italy and other European countries with similar social profiles to reach the target uptake., (© 2024. The Author(s).)

Background: Streptococcus pneumoniae infections, including Invasive Pneumococcal Diseases (IPDs), pose a substantial public health challenge, causing significant morbidity and mortality, especially among children and older adults. Vaccination campaigns have played a vital role in reducing pneumococcal-related deaths. However, obstacles related to accessibility and awareness might impede optimal vaccine adoption. This study aims to provide comprehensive data on pneumococcal vaccine coverage and attitudes within at-risk groups in Italy, with the goal of informing public health strategies and addressing vaccination barriers., Methods: Between April 11 and May 29, 2022, a questionnaire investigating vaccine uptake and attitudes toward several vaccinations was administered to 10,000 Italian adults, chosen through population-based sampling. Respondents who were targets of the campaign according to the 2017-2019 National Vaccination Plan, accessed questions regarding pneumococcal vaccination. Data on uptake, awareness of having the right to free vaccination, opinion on vaccine safety, concern with pneumococcal disease, and ease of access to vaccination services were summarized and presented based on statistical regions. Multinomial logistic regression analysis was used to explore factors influencing vaccine uptake., Results: Out of 2357 eligible adult respondents (42.6% women; mean age: 58.1 ± 15.7), 39.5% received pneumococcal vaccination. Uptake differed among at-risk groups: respondents aged ≥65 (33.7%), with lung disease (48.4%), cardiovascular disease (46.6%), and diabetes (53.7%). Predictors of not being vaccinated and unwilling to included female gender, residing in rural areas, lower education, low concern about pneumococcal disease, vaccine safety concerns, and associations with vaccine-opposed acquaintances. Health access issues predicted willingness to be vaccinated despite non-vaccination. Pneumopathy, heart disease, diabetes, and living in Northeastern or Central Italy were linked to higher uptake. Among the 1064 parents of eligible children, uptake was 79.1%. Parental unawareness of children's free vaccination eligibility was a predictor of non-vaccination. Vaccine safety concerns correlated with reluctance to vaccinate children, while perceived healthcare access challenges were associated with wanting but not having received vaccination., Conclusions: Pneumococcal vaccination uptake within prioritized groups and children in Italy remains inadequate. Scarce awareness of vaccine availability and obstacles in accessing vaccinations emerge as principal barriers influencing this scenario., (© 2024. The Author(s).)

Background: Human Papillomavirus (HPV) vaccination rates are still below the target due to vaccine refusal or delay, lack of knowledge, and logistical challenges. Understanding these barriers is crucial for developing strategies to improve HPV vaccination rates., Methods: This cross-sectional study used a questionnaire to investigate social and behavioral factors influencing decision making about the HPV vaccine. The survey was conducted from 11 April to 29 May 2022 and involved 10,000 Italian citizens aged ≥ 18 years. The sample was stratified based on region of residence, gender, and age group., Results: 3160 participants were surveyed about themselves, while 1266 respondents were surveyed about their children's vaccine uptake. Among females aged ≥ 26 years, the national average HPV vaccine uptake was 21.7%, with variations across different regions. In the 18-25 age group, females had a vaccine uptake (80.8%) twice as much as males (38.1%), while vaccine uptake among male and female children aged 9-11 was similar., Conclusions: The OBVIOUS study in Italy reveals factors influencing low HPV vaccine uptake, suggesting targeted approaches, tailored information campaigns, heightened awareness of eligibility, promoting early vaccination, addressing low-risk perception among males, addressing safety concerns, and enhancing perceived accessibility to improve vaccine uptake and mitigate health risks.

Influenza annually claims an estimated 8,000 lives in Italy. Despite no-cost vaccinations for high-risk groups, hesitancy persists. This study aims to pinpoint social and behavioral vaccination determinants, forming strategies to bolster vaccine uptake. From April 11 to May 29, 2022, we surveyed a demographic-stratified sample of 10,000 Italian adults, employing the WHO's Behavioral and Social Drivers of Vaccination (BesD) framework. Of those, 4,613 (46.1%) were eligible for the influenza vaccine and included in the analysis. Roughly a third remained unvaccinated and unwilling. Central Italy showed the highest resistance, with significant percentages of seniors and professionals like teachers, law enforcement, and healthcare workers expressing noncompliance. A lack of awareness of being in a target group correlated significantly with vaccine refusal or delayed acceptance. Other refusal factors included female gender, being aged 45-54, rural residency, absence of higher education, perceived vaccine unsafety, and having vaccine-opposed acquaintances. Thus, addressing these perceptions and enhancing awareness can potentially increase vaccination rates and lessen disease impact.

Abstract., Objective: The aim of this study is to evaluate male awareness of developing prostate cancer (PCa) in families with germline DNA-repair genes (DRG) variants., Materials and Methods: Data were collected from a prospective, monocentric cohort study. The study was conducted in a university hospital with a multidisciplinary approach to the patient (collaboration of the Departments of Oncology, Urology, Pathology, Radiology, and Medical Genetics Laboratory). We recruited healthy males, relatives of families of women with breast or ovarian cancer who tested positive for pathogenic variants (PVs) or likely pathogenic variants (LPVs) in DRGs. A dedicated PCa screening was designed and offered to men aged 35 to 69 years, based on early visits with digital rectal examination (DRE), prostate health index (PHI) measurement, multiparametric magnetic resonance imaging (mpMRI) and, if necessary, targeted/systematic prostate biopsies. The primary endpoint was to evaluate the willingness of healthy men from families with a DRG variants detected in female relatives affected with breast and/or ovarian cancer to be tested for the presence of familial PVs. The secondary endpoints were the acceptance to participate if resulted positive and compliance with the screening programme., Results: Over 1256 families, of which 139 resulted positive for PVs in DRGs, we identified 378 'healthy' men aged between 35 and 69 years old. Two hundred sixty-one (69.0%) refused to be tested for DRG variants, 66 (17.5%) declared to have been previously tested, and 51 (13.5%) males were interested to be tested. Between those previously tested and those who accepted to be tested, 62 (53.0%) were positive for a DRG variant, and all of them accepted to participate in the subsequent surveillance steps. The main limitation is that is a single-centre study and a short follow-up., Conclusions: All men tested positive for a DRG variants agreed to go under the surveillance scheme. However, only 31% of 'men at risk' (i.e., relative of a DRG variant carrier) expressed their willingness to be tested for the familial DRG variant. This observation strongly supports the urgent need to implement awareness of genetic risk for PCa within the male population., Competing Interests: All authors declare no conflict of interest., (© 2023 The Authors. BJUI Compass published by John Wiley & Sons Ltd on behalf of BJU International Company.)

Liquid biopsy (LB) for prostate cancer (PCa) detection could represent an alternative to biopsy. Seminal fluid (SF) is a source of PCa-specific biomarkers, as 40% of ejaculate derives from the prostate. We tested the feasibility of an SF-based LB by evaluating the yield of semen self-sampling in a cohort of >750 patients with clinically localized PCa. The overall SF collection yield was 18.2% (39% when considering only compliant patients), with about a half of the patients (53.15%) not consenting to SF donation. Independent favorable predictors for SF collection were younger age and lower prostate volume. We implemented a protocol to enrich prostate-derived cells by multi-color flow cytometry and applied it on SF and urine samples from 100 patients. The number of prostate-enriched cells (SYTO-16+ PSMA+ CD45-) was variable, with higher numbers of cells isolated from SF than urine ( p value < 0.001). Putative cancer cells (EpCAM high ) were 2% of isolated cells in both specimens. The fraction of EpCAM high cells over prostate-enriched cells (PSMA+) significantly correlated with patient age in both semen and urine, but not with other clinical parameters, such as Gleason Score, ISUP, or TNM stage. Hence, enumeration of prostate-derived cells is not sufficient to guide PCa diagnosis; additional molecular analyses to detect patient-specific cancer lesions will be needed.

Background: Vaccine hesitancy was defined by the World Health Organization (WHO) in 2019 as a major threat to global health. In Italy, reluctance to receive vaccines is a widespread phenomenon that was amplified during the COVID-19 pandemic by fear and mistrust in government. This study aims to depict different profiles and characteristics of people reluctant to vaccinate, focusing on the drivers of those who are in favor of and those who are opposed to receiving the COVID-19 vaccine., Methods: A sample of 10,000 Italian residents was collected. A survey on COVID-19 vaccination behavior and possible determinants of vaccine uptake, delay, and refusal was administered to participants through a computer-assisted web interviewing method., Results: In our sample, 83.2% stated that they were vaccinated as soon as possible ("vaccinators"), 8.0% delayed vaccination ("delayers"), and 6.7% refused to be vaccinated ("no-vaccinators"). In general, the results show that being female, aged between 25 and 64, with an education level less than a high school diploma or above a master's degree, and coming from a rural area were characteristics significantly associated with delaying or refusing COVID-19 vaccination. In addition, it was found that having minimal trust in science and/or government (i.e., 1 or 2 points on a scale from 1 to 10), using alternative medicine as the main source of treatment, and intention to vote for certain parties were characteristics associated with profiles of "delayers" or "no-vaccinators". Finally, the main reported motivation for delaying or not accepting vaccination was fear of vaccine side effects (55.0% among delayers, 55.6% among no-vaccinators)., Conclusion: In this study, three main profiles of those who chose to be vaccinated are described. Since those who are in favor of vaccines and those who are not usually cluster in similar sociodemographic categories, we argue that findings from this study might be useful to policy makers when shaping vaccine strategies and choosing policy instruments.

Objectives: There is little evidence on the impact of the COVID-19 pandemic on Public Health Residents' (PHR) mental health (MH). This study aims at assessing prevalence and risk factors for depression, anxiety and stress in European PHR during the COVID-19 pandemic., Methods: Between March and April 2021, an online survey was administered to PHR from France, Italy, Portugal and Spain. The survey assessed COVID-19 related changes in working conditions, training opportunities and evaluated MH outcomes using the Depression Anxiety Stress Scales-21. Multivariable logistic regressions were applied to identify risk factors., Results: Among the 443 respondents, many showed symptoms of depression (60.5%), anxiety (43.1%) and stress (61.2%). The main outcome predictors were: female gender for depression (adjOR = 1.59, 95%CI [1.05-2.42]), anxiety (adjOR = 2.03, 95%CI [1.33-3.08]), and stress (adjOR = 2.35, 95%CI [1.53-3.61]); loss of research opportunities for anxiety (adjOR = 1.94, 95%CI [1.28-2.93]) and stress (adjOR = 1.98, 95%CI [1.26-3.11]); and COVID-19 impact on training (adjOR = 1.78, 95%CI [1.12-2.80]) for depression., Conclusions: The pandemic had a significant impact on PHR in terms of depression, anxiety and stress, especially for women and who lost work-related opportunities. Training programs should offer PHR appropriate MH support and training opportunities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Failla, Caminiti, Chen-Xu, Lo Moro, Berselli, Cabral Ferreira, Malcata, Peyre-Costa, Croci, Soldà, Capodici, Morcavallo, Traglia, Cedrone, Storti, Jaquete, Antinozzi and Vasiliu.)

Regular physical activity (PA) is protective and reduces disease burden but remains a challenge for pregnant women (PW). According to the World Health Organization (WHO) guidelines, PW without contraindications should practice 150 min of moderate PA per week. Nonetheless, PA levels are concerningly low among PW. The aim of this study was to investigate PW's and midwives' perceptions regarding PA and recommended guidelines, and use this information to inform future health promotion strategies. We recruited 10 PW and 10 midwives to participate in online focus groups conducted between July 2020 and April 2021. Focus group probes and data analysis were guided by the COM-B (capability, opportunity, motivation-behaviour) framework. The majority of the sample had already practised PA, recognized the importance of PA during pregnancy, and considered the WHO guidelines reasonable. Notwithstanding, PW wanted more specific instruction on PA and desired opportunities to practice. Additional barriers reported by PW included low self-efficacy and lack of motivation. Midwives considered the lack of specific knowledge and confidence in managing PA as the main obstacles. The current findings suggest that PW and midwives need specific training in PA to overcome both psychological and physical barriers. Midwives play a vital role in educating and encouraging PA among PW.

Diaphanous related formins are regulatory cytoskeletal protein involved in actin elongation and microtubule stabilization. In humans, defects in two of the three diaphanous genes (DIAPH1 and DIAPH3) have been associated with different types of hearing loss. Here, we investigate the role of the third member of the family, DIAPH2, in nonsyndromic hearing loss, prompted by the identification, by exome sequencing, of a predicted pathogenic missense variant in DIAPH2. This variant occurs at a conserved site and segregated with nonsyndromic X-linked hearing loss in an Italian family. Our immunohistochemical studies indicated that the mouse ortholog protein Diaph2 is expressed during development in the cochlea, specifically in the actin-rich stereocilia of the sensory outer hair cells. In-vitro studies showed a functional impairment of the mutant DIAPH2 protein upon RhoA-dependent activation. Finally, Diaph2 knock-out and knock-in mice were generated by CRISPR/Cas9 technology and auditory brainstem response measurements performed at 4, 8 and 14 weeks. However, no hearing impairment was detected. Our findings indicate that DIAPH2 may play a role in the inner ear; further studies are however needed to clarify the contribution of DIAPH2 to deafness., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Chiereghin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Circular RNAs (circRNAs) are a class of non-coding RNAs increasingly emerging as crucial actors in the pathogenesis of human diseases, including autoimmune and neurological disorders as multiple sclerosis (MS). Despite several efforts, the mechanisms regulating circRNAs expression are still largely unknown and the circRNA profile and regulation in MS-relevant cell models has not been completely investigated. In this work, we aimed at exploring the global landscape of circRNA expression in MS patients, also evaluating a possible correlation with their genetic and epigenetic background., Methods: We performed RNA-seq experiments on circRNA-enriched samples, derived from peripheral blood mononuclear cells (PBMCs) of 10 MS patients and 10 matched controls and performed differential circRNA expression. The genetic background was evaluated using array genotyping, and an expression quantitative trait loci (eQTL) analysis was carried out., Results: Expression analysis revealed 166 differentially expressed circRNAs in MS patients, 125 of which are downregulated. One of the top dysregulated circRNAs, hsa&#95;circ&#95;0007990, derives from the PGAP3 gene, encoding a protein relevant for the control of autoimmune responses. The downregulation of this circRNA was confirmed in two independent replication cohorts, suggesting its implementation as a possible RNA-based biomarker. The eQTL analysis evidenced a significant association between 89 MS-associated loci and the expression of at least one circRNA, suggesting that MS-associated variants could impact on disease pathogenesis by altering circRNA profiles. Finally, we found a significant correlation between exon methylation and circRNA expression levels, supporting the hypothesis that epigenetic features may play an important role in the definition of the cell circRNA pool., Conclusion: We described the circRNA expression profile of PBMCs in MS patients, suggesting that MS-associated variants may tune the expression levels of circRNAs acting as "circ-QTLs", and proposing a role for exon-based DNA methylation in regulating circRNA expression., Competing Interests: Declaration of Competing Interest The authors report no conflict of interest., (Copyright © 2022. Published by Elsevier B.V.)

Objectives: To test the hypothesis of a relationship between a specific genetic lesion (T2:ERG) and imaging scores, such as PI-RADS and PRI-MUS, and to test the effectiveness of these parameters for the diagnosis of prostate cancer (PCa) and clinically significant PCa (csPCa)., Materials and Methods: This is a prospective study of men with suspected PCa enrolled between 2016 and 2019 at a high-volume tertiary hospital. Patients underwent systematic US-guided biopsy, plus targeted biopsy if they were presenting with >=1 suspicious lesion (PI-RADS>2) at mpMRI or PR-IMUS >2 at micro-ultrasound assessment. For each patient, one core from the highest PI-RADS or PRI-MUS lesion was collected for T2:ERG analysis. Multivariable logistic regression models (LRMs) were fitted for csPCa with a clinical model (age, total PSA, previous biopsy, family history for PCa), a clinical plus PI-RADS, clinical plus T2:ERG, clinical plus PI-RADS plus T2:ERG, and T2:ERG plus PI-RADS alone., Results: The cohort consists of 158 patients: 83.5% and 66.2% had respectively a diagnosis of PCa and csPCa after biopsy. A T2:ERG fusion was found in 37 men and 97.3% of these patients harbored PCa, while 81.1% were diagnosed with csPCa. SE of T2:ERG assay for csPCa was 28.8%, SP 87.0%, NPV 38.8%, and PPV 81.1%. Of 105 patients who performed mpMRI 93.% had PIRADS ≥3. SE of mpMRI for csPCa was 98.5%, SP was 12.8%, NPV was 83.3%, and PPV was 65.7%. Among 67 patients who were subjected to micro-US, 90% had a PRI-MUS ≥3. SE of micro-US for csPCa was 89.1%, SP was 9.52%, NPV was 28.6%, and PPV was 68.3%. At univariable LRM T2:ERG was confirmed as independent of mpMRI and micro-US result (OR 1.49, p=0.133 and OR 1.82, p=0.592, respectively). At multivariable LRM the clinical model alone had an AUC for csPCa of 0.74 while the clinical model including PI-RADS and T2:ERG achieved an AUC of 0.83., Conclusions: T2:ERG translocation and imaging results are independent of each other, but both are related csPCa. To evaluate the best diagnostic work-up for PCa and csPCa detection, all available tools (T2:ERG detection and imaging techniques) should be employed together as they appear to have a complementary role., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lazzeri, Fasulo, Lughezzani, Benetti, Soldà, Asselta, De Simone, Paciotti, Avolio, Contieri, Saitta, Saita, Hurle, Guazzoni, Buffi and Casale.)