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Abstract Background Indigenous peoples globally continue to be underrepresented in biomarker, genomic, and biobanking research. The aim of this study was to identify core components of culturally safe and ethical biomarker and genomic research with Indigenous peoples in Australia, Aotearoa/New Zealand, Canada and the USA. Methods A scoping review with a systematic search strategy was conducted utilising electronic databases MEDLINE, EMBASE, PsychINFO, CINAHL and Global Health. Key search terms included ‘biomarkers’ and ‘genomics’ research involving Indigenous peoples in relation to ethical and legal principles of respect, sovereignty, governance and existing policies. Original research studies published from the year 2000 to the 1st of August 2023 were reviewed in a systematic manner. Components of culturally safe and ethical research processes were identified and synthesised descriptively. The quality of included studies was assessed using an Aboriginal and Torres Strait Islander Quality Appraisal Tool through an Indigenous lens. Results Seven interrelated research components were identified from seventeen studies as core processes to enhance the cultural safety of biomarker and genomic research. These included building relationships and community engagement, learning, research coordination, logistics, consent, samples and biospecimens, biobank structures and protections and policy. The importance of ensuring self-determination, ownership and decision-making power is emphasised in processes to establish and conduct biomarker and genomic research with Indigenous peoples. Conclusions Components that contribute to the cultural safety of biomarker and genomic research processes identified in this scoping review were assembled into a theoretical framework to guide research practice. Further evaluation is required by Indigenous peoples and communities to appropriate and adapt this framework for local use to promote the cultural safety of research processes and minimise barriers to Indigenous peoples’ participation in biomarker and genomic research.

Purpose: The aim of this study is to develop a framework for quantitative analysis of longitudinal T2-weighted MRIs (T2w) following radiotherapy (RT) for prostate cancer. Materials and methods: The developed methodology includes: (i) deformable image registration of longitudinal series to pre-RT T2w for automated detection of prostate, peripheral zone (PZ), and gross tumor volume (GTV); and (ii) T2w signal-intensity harmonization based on three reference tissues. The REgistration and HARMonization (REHARM) framework was applied on T2w acquired in a clinical trial consisting of two pre-RT and three post-RT MRI exams. Image registration was assessed by the DICE coefficient between automatic and manual contours, and intensity normalization via inter-patient histogram intersection. Longitudinal consistency was evaluated by the repeatability coefficient and Pearson correlation (r) between the two T2w exams before RT. Results: T2w from 107 MRI exams (23 patients) were utilized. Following REHARM, the histogram intersections for prostate, PZ and GTV increased from median = 0.43/0.16/0.13 to 0.66/0.44/0.46. The repeatability in T2w intensity estimation was better for the automatic than the manual contours for all three regions of interest (r = 0.9, p

BackgroundPatients with prostate cancer undergoing radiation therapy (RT) need comfortably full bladders to reduce toxicities during treatment. Poor compliance is common with standard of care written or verbal instructions, leading to wasted patient value (PV) and clinic resources via poor throughput efficiency (TE). ObjectiveHerein, we assessed the feasibility and acceptability of a smartphone-based behavioral intervention (SBI) to improve bladder-filling compliance and methods for quantifying PV and TE. MethodsIn total, 36 patients with prostate cancer were enrolled in a single-institution, closed-access, nonrandomized feasibility trial. The SBI consists of a fully automated smart water bottle and smartphone app. Both pieces alert the patient to empty his bladder and drink a personalized volume goal, based on simulation bladder volume, 1.25 hours before his scheduled RT. Patients were trained to adjust their volume goal and notification times to achieve comfortably full bladders. The primary end point was met if qualitative (QLC) and quantitative compliance (QNC) were >80%. For QLC, patients were asked if they prepared their bladders before daily RT. QNC was met if bladder volumes on daily cone-beam tomography were >75% of the simulation’s volume. The Service User Technology Acceptability Questionnaire (SUTAQ) was given in person pre- and post-SBI. Additional acceptability and engagement end points were met if >3 out of 5 across 4 domains on the SUTAQ and >80% (15/18) of patients used the device >50% of the time, respectively. Finally, the impact of SBI on PV and TE was measured by time spent in a clinic and on the linear accelerator (linac), respectively, and contrasted with matched controls. ResultsQLC was 100% in 375 out of 398 (94.2%) total treatments, while QNC was 88.9% in 341 out of 398 (85.7%) total treatments. Of a total score of 5, patients scored 4.33 on privacy concerns, 4 on belief in benefits, 4.56 on satisfaction, and 4.24 on usability via SUTAQ. Further, 83% (15/18) of patients used the SBI on >50% of treatments. Patients in the intervention arm spent less time in a clinic (53.24, SEM 1.71 minutes) compared to the control (75.01, SEM 2.26 minutes) group (P

Abstract Extracting longitudinal image quantitative data, known as delta-radiomics, has the potential to capture changes in a patient’s anatomy throughout the course of radiation treatment for prostate cancer. Some of the major challenges of delta-radiomics studies are contouring the structures for individual fractions and accruing patients’ data in an efficient manner. The manual contouring process is often time consuming and would limit the efficiency of accruing larger sample sizes for future studies. The problem is amplified because the contours are often made by highly trained radiation oncologists with limited time to dedicate to research studies of this nature. This work compares the use of automated prostate contours generated using a deformable image-based algorithm to make predictive models of genitourinary and changes in total international prostate symptom score in comparison to manually contours for a cohort of fifty patients. Area under the curve of manual and automated models were compared using the Delong test. This study demonstrated that the delta-radiomics models were similar for both automated and manual delta-radiomics models.

Carnitine palmitoyltransferase II (CPT II) deficiency is an autosomal recessive inherited disorder related to lipid metabolism affecting skeletal muscle. The first cases of CPT II deficiency causing myopathy were reported in 1973. In 1983, Werneck et al published the first two Brazilian patients with myopathy due to CPT II deficiency, where the biochemical analysis confirmed deficient CPT activity in the muscle of both cases. Over the past 40 years since the pioneering publication, clinical phenotypes and genetic loci in the CPT2 gene have been described, and pathogenic mechanisms have been better elucidated. Genetic analysis of one of the original cases disclosed compound heterozygous pathogenic variants (p.Ser113Leu/p.Pro50His) in the CPT2 gene. Our report highlights the historical aspects of the first Brazilian publication of the myopathic form of CPT II deficiency and updates the genetic background of this pioneering publication.

Background Myasthenia gravis (MG) is an autoimmune disease usually caused by antibodies against the acetylcholine receptor (AChR-Abs), muscle-specific tyrosine kinase (MuSK-Abs), or low-density lipoprotein receptor-related protein 4 (LRP4-Abs). However, there are MG patients who do not have these antibodies and are thus said to have triple-seronegative (triple-SN) MG.

The INFN–CNAF Tier-1 located in Bologna (Italy) is a center of the WLCG e-Infrastructure providing computing power to the four major LHC collaborations and also supports the computing needs of about fifty more groups - also from non HEP research domains. The CNAF Tier1 center has been historically very active putting effort in the integration of computing resources, proposing and prototyping solutions both for extension through Cloud resources, public and private, and with remotely owned sites, as well as developing an integrated HTC+HPC system with the PRACE CINECA supercomputer center located 8Km far from the CNAF Tier-1 located in Bologna. In order to meet the requirements for the new Tecnopolo center, where the CNAF Tier-1 will be hosted, the resource integration activities keep progressing. In particular, this contribution will detail the challenges that have recently been addressed, providing opportunistic access to non standard CPU architectures, such as PowerPC and hardware accelerators (GPUs). We explain the approach adopted to both transparently provision x86_64, ppc64le and NVIDIA V100 GPUs from the Marconi 100 HPC cluster managed by CINECA and to access data from the Tier1 storage system at CNAF. The solution adopted is general enough to enable seamless integration of other computing architectures at the same time from different providers, such as ARM CPUs from the TEXTAROSSA project, and we report about the integration of these within the computing model of the CMS experiment. Finally we will discuss the results of the early experience.

The ML_INFN initiative (“Machine Learning at INFN”) is an effort to foster Machine Learning (ML) activities at the Italian National Institute for Nuclear Physics (INFN). In recent years, artificial intelligence inspired activities have flourished bottom-up in many efforts in Physics, both at the experimental and theoretical level. Many researchers have procured desktop-level devices, with consumer-oriented GPUs, and have trained themselves in a variety of ways, from webinars, books, and tutorials. ML_INFN aims to help and systematize such effort, in multiple ways: by offering state-of-the-art hardware for ML, leveraging on the INFN Cloud provisioning solutions and thus sharing more efficiently GPUs and leveling the access to such resources to all INFN researchers, and by organizing and curating Knowledge Bases with productiongrade examples from successful activities already in production. Moreover, training events have been organized for beginners, based on existing INFN ML research and focused on flattening the learning curve. In this contribution, we will update the status of the project reporting in particular on the development of tools to take advantage of High-Performance Computing resources provisioned by CNAF and ReCaS computing centers for interactive support to activities and on the organization of the first in-person advanced-level training event, with a GPU-equipped cloud-based environment provided to each participant.

The INFN Tier1 data center is currently located in the premises of the Physics Department of the University of Bologna, where CNAF is also located. During 2023 it will be moved to the “Tecnopolo”, the new facility for research, innovation, and technological development in the same city area; the same location is also hosting Leonardo, the pre-exascale supercomputing machine managed by CINECA, co-financed as part of the EuroHPC Joint Undertaking, 4th ranked in the top500 November 2022 list. The construction of the new CNAF data center consists of two phases, corresponding to the computing requirements of LHC: Phase 1 involves an IT power of 3 MW, and Phase 2, starting from 2025, involves an IT power up to 10 MW. The new data center is designed to cope with the computing requirements of the data taking of the HL-LHC experiments, in the time spanning from 2026 to 2040 and will provide, at the same time, computing services for several other INFN experiments and projects, not only belonging to the HEP domain. The co-location with Leonardo opens wider possibilities to integrate HTC and HPC resources and the new CNAF data center will be tightly coupled with it, allowing access from a single entry point to resources located at CNAF and provided by the supercomputer. Data access from both infrastructures will be transparent to users. In this presentation we describe the new data center design, providing a status update on the migration, and we focus on the Leonardo integration showing the results of the preliminary tests to access it from the CNAF access points.

Optical bioimaging is an ever‐growing field that benefits both from the fast progress of optical instrumentation and modalities, and from the development of light‐emitting probes. The efficacy of molecular fluorescent dyes is crucial, yet hindered by limited brightness and hydrophilicity. Addressing these challenges, self‐stabilized fluorogenic organic nanoparticles only made of pure dyes (dFONs) are introduced in this work. Comprising thiol‐sensitive fluorogenic chromophores, these dFONs exhibit enhanced brightness exclusively in the presence of biological thiols, notably glutathione, overcoming the need for water‐solubilizing moieties. Importantly, these nanoparticles demonstrate large fluorescence and one‐ and two‐photon brightness, enabling sensitive bioimaging of intracellular thiols at micromolar concentrations. Notably, only the pristine fluorogenic nanoparticles can penetrate the cells and does not require to wash the cells before imaging, emphasizing their unique role as dye carriers, fluorogenic probes and ease of use. This work highlights the transformative potential of dFONs in advancing optical bioimaging, paving the way for the use of dFONs not just as tracers, but also now as biosensors and ultimately in the future as biomarkers. [ABSTRACT FROM AUTHOR]

To assess the relationship between smoking exposure and organ damage accrual measured by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index for Systemic Lupus Erythematosus score (SLICC-SDI) in consecutive patients with systemic lupus erythematosus (SLE) from Argentina.623 consecutive SLE patients (fulfilling ≥4, 1997 ACR criteria) were included in this cross-sectional study. Sociodemographic and disease related variables including SLICC-SDI score and smoking status were collected. Patients currently smoking were considered “smokers”, and “non-smokers” those who never smoked and former smokers. SLICC-SDI was divided into two categories: <3 and ≥3 was defined as severe damage.Six hundred and 23 patients were included in the analysis, 89% women. Eighty-four per cent were non-smokers and 16 % were current smokers 83 percent of patients had SLICC-SDI <3 and 17 % had SLICC-SDI ≥3. Twenty one percent of patients with SLICC-SDI ≥3 and 15% with <3 SLICC-SDI were current smokers (p 0.081). In the multiple regression analysis, current smoking (OR 1.82, CI 95% 1.01-3.31, p 0.046), older age (OR 1.04, CI 95% 1.00-1.05, p 0.034), disease duration (OR 1.03, CI 95% 1.00-1.07, p 0.021) and cyclophosphamide exposure (OR 2.97, CI 95% 1.49-5.88, p 0.002) were related to SLICC-SDI ≥3.In our sample of patients, current smoking, older age, disease duration and cyclophosphamide were related to severe damage (SLICC-SDI ≥3). [ABSTRACT FROM AUTHOR]

Background: 4Kscore is used to aid the decision for prostate biopsy, however its role in active surveillance (AS) has not been investigated in a magnetic resonance imaging (MRI)-based protocol. Our objective was to assess the association between 4Kscore and progression in men undergoing AS on a prospective MRI-based protocol., Methods: This was a single-institution, single-arm, non-therapeutic, interventional trial of 166 men with biopsy-confirmed prostate cancer enrolled between 2014-2020. Patients were placed on a trial-mandated AS protocol including yearly multiparametric (mp)MRI, prostate biopsy, and 4Kscore followed for 48 months after diagnosis. We analyzed protocol-defined and grade progression at confirmatory and subsequent surveillance biopsies., Results: Out of 166 patients, 83 (50%) men progressed per protocol and of them 41 (24.7% of whole cohort) progressed by grade. At confirmatory biopsy, men with a baseline 4Kscore ≥ 20% had a higher risk of grade progression compared to those with 4Kscore < 20% (OR = 4.04, 95% CI: 1.05-15.59, p = 0.043) after adjusting for National Comprehensive Cancer Network (NCCN) risk and baseline PIRADS score. At surveillance biopsies, most recent 4Kscore ≥ 20% significantly predicted per protocol (OR = 2.61, 95% CI: 1.03-6.63, p = 0.044) and grade progression (OR = 5.13, 95% CI: 1.63-16.11, p = 0.005)., Conclusions: For patients on AS, baseline 4Kscore predicted grade progression at confirmatory biopsy, and most recent 4Kscore predicted per-protocol and grade progression at surveillance biopsy., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Patients with prostate cancer undergoing radiation therapy (RT) need comfortably full bladders to reduce toxicities during treatment. Poor compliance is common with standard of care written or verbal instructions, leading to wasted patient value (PV) and clinic resources via poor throughput efficiency (TE)., Objective: Herein, we assessed the feasibility and acceptability of a smartphone-based behavioral intervention (SBI) to improve bladder-filling compliance and methods for quantifying PV and TE., Methods: In total, 36 patients with prostate cancer were enrolled in a single-institution, closed-access, nonrandomized feasibility trial. The SBI consists of a fully automated smart water bottle and smartphone app. Both pieces alert the patient to empty his bladder and drink a personalized volume goal, based on simulation bladder volume, 1.25 hours before his scheduled RT. Patients were trained to adjust their volume goal and notification times to achieve comfortably full bladders. The primary end point was met if qualitative (QLC) and quantitative compliance (QNC) were >80%. For QLC, patients were asked if they prepared their bladders before daily RT. QNC was met if bladder volumes on daily cone-beam tomography were >75% of the simulation's volume. The Service User Technology Acceptability Questionnaire (SUTAQ) was given in person pre- and post-SBI. Additional acceptability and engagement end points were met if >3 out of 5 across 4 domains on the SUTAQ and >80% (15/18) of patients used the device >50% of the time, respectively. Finally, the impact of SBI on PV and TE was measured by time spent in a clinic and on the linear accelerator (linac), respectively, and contrasted with matched controls., Results: QLC was 100% in 375 out of 398 (94.2%) total treatments, while QNC was 88.9% in 341 out of 398 (85.7%) total treatments. Of a total score of 5, patients scored 4.33 on privacy concerns, 4 on belief in benefits, 4.56 on satisfaction, and 4.24 on usability via SUTAQ. Further, 83% (15/18) of patients used the SBI on >50% of treatments. Patients in the intervention arm spent less time in a clinic (53.24, SEM 1.71 minutes) compared to the control (75.01, SEM 2.26 minutes) group (P<.001). Similarly, the intervention arm spent less time on the linac (10.67, SEM 0.40 minutes) compared to the control (14.19, SEM 0.32 minutes) group (P<.001)., Conclusions: This digital intervention trial showed high rates of bladder-filling compliance and engagement. High patient value and TE were feasibly quantified by shortened clinic times and linac usage, respectively. Future studies are needed to evaluate clinical outcomes, patient experience, and cost-benefit., Trial Registration: ClinicalTrials.gov NCT04946214; https://www.clinicaltrials.gov/study/NCT04946214., (©William Jin, Christopher Montoya, Benjamin James Rich, Crystal Seldon Taswell, Miguel Noy, Deukwoo Kwon, Benjamin Spieler, Brandon Mahal, Matthew Abramowitz, Raphael Yechieli, Alan Pollack, Alan Dal Pra. Originally published in JMIR Cancer (https://cancer.jmir.org), 10.09.2024.)