Search

Abstract Objectives To test the Reason for Exam Imaging Reporting and Data System (RI-RADS) in assessing the quality of radiology requests in an Italian cohort of inpatients; to evaluate the interobserver reliability of RI-RADS. Methods A single-center quality care study was designed to retrospectively identify consecutive radiology request forms for computed tomography, magnetic resonance imaging, and conventional radiography examinations. One radiologist scored the requests using the RI-RADS. The association between RI-RADS and clinical request variables (urgent request, on-call requests, indication for imaging, requesting specialty, imaging modality, and body region) was evaluated. We calculated interobserver agreement between four readers in a subset of 450 requests. Results We included 762 imaging requests. RI-RADS grades A (adequate request), B (barely adequate request), C (considerably limited request), D (deficient request), and X were assigned to 8 (1%), 49 (7%), 237 (31%), 404 (53%), and 64 (8%) of cases, respectively. In the multivariate analysis, the indication for imaging, body region, and requesting specialty significantly influenced the RI-RADS. Indications for imaging with a high risk of poor RI-RADS grade were routine preoperative imaging and device check requests. The upper extremity was the body region with the highest risk of poor RI-RADS grade. Requesting specialties with a high risk of poor RI-RADS grade were cardiovascular surgery, intensive care medicine, and orthopedics. The analysis of the interobserver agreement revealed substantial agreement for the RI-RADS grade. Conclusion The majority of radiology exam requests were inadequate according to RI-RADS, especially those for routine imaging. RI-RADS demonstrated substantial reliability, suggesting that it can be satisfactorily employed in clinical settings. Critical relevant statement The implementation of RI-RADS can provide a framework for standardizing radiology requests, thereby enabling quality assurance and promoting a culture of quality improvement. Key Points RI-RADS aims to grade the completeness of radiology requests. Over half of the imaging requests were RI-RADS D grade; RI-RADS demonstrated substantial reliability. Most radiology requests were inadequate and RI-RADS could classify them in clinical practice. Graphical Abstract

Abstract Background Nuts consumption is related to cardioprotective effects on primary cardiovascular prevention, but studies conducted in secondary prevention are small, scarce and controversial. The objective of this trial was to evaluate the effects of a regional and sustainable cardioprotective diet added or not with an affordable mixed nuts on cardiometabolic features in patients with previous myocardial infarction. Methods DICA-NUTS study is a national, multi-center, and superiority-parallel randomized clinical trial. Males and females over 40 years old diagnosed with previous myocardial infarction in the last 2 to 6 months were included. Patients were allocated into two groups: the Brazilian Cardioprotective diet (DICA Br) supplemented with 30 g/day of mixed nuts (10 g of peanuts; 10 g of cashew; 10 g of Brazil nuts) (intervention group, n = 193); or only DICA Br prescription (control group, n = 195). The primary outcome was low-density lipoprotein cholesterol means (in mg/dL) after 16 weeks. Secondary outcomes were other lipid biomarkers, glycemic and anthropometric data and diet quality. Results After adjustment for baseline values, participating study site, time since myocardial infarction and statin treatment regimen (high potency, moderate and low potency/no statins), no significant difference was found between the groups in low-density lipoprotein cholesterol concentrations (intervention-control difference: 3.48 mg/dL [-3.45 to 10.41], P = 0.32). Both groups improved their overall diet quality at the end of the study without differences between them after 16 weeks (intervention-control difference: 1.05 (-0.9 to 2.99); P = 0.29). Other lipids, glycemic profile and anthropometrics were also not different between study groups at the end of the study. Conclusion Adding 30 g/day of mixed nuts to the DICA Br for 16 weeks did not change lipid, glycemic and anthropometric features in the post-myocardial infarction setting. Trial registration This study is registered on ClinicalTrials.gov website under number NCT03728127 and its World Health Organization Universal Trial Number (WHO-UTN) is U1111-1259–8105.

Backgrounds/Aims Atezolizumab/bevacizumab is the recommended first-line systemic therapy for unresectable hepatocellular carcinoma (uHCC) and may facilitate curative conversion through resection and locoregional therapies. However, there have been very few reports on curative conversion using microwave ablation (MWA). This study aimed to determine the curative conversion rate with MWA using atezolizumab-bevacizumab as the first-line treatment in patients with uHCC, and to compare the characteristics and survival of patients with and without curative conversion. Methods Consecutive patients with uHCC who were started on atezolizumab-bevacizumab from May 2021 to December 2023 in a single tertiary center were included. Objective response rate (ORR) and disease control rate (DCR) were based on the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 and modified RECIST (mRECIST) criteria. Results Twenty consecutive patients with uHCC (60% advanced-stage) were included, 90% exceeding the up-to-7 criteria. The ORR and DCR were 35% and 60%, 35% and 55% using RECIST and mRECIST, respectively. Five patients (25%) underwent successful curative conversion with MWA (four advanced and one intermediate stage) despite a median HCC size of 6.1 cm (range, 2.4-7.3). Two of these patients were tumor and drug-free 132-133 weeks from the 1st atezolizumab-bevacizumab dose. Patients who underwent curative conversion had significantly longer survival than those who did not (P=0.024). Other factors associated with survival were male sex, Child-Pugh class A, and an objective response. Conclusions Despite the relatively large tumor size, successful curative conversion with MWA was achieved with first-line atezolizumab-bevacizumab in uHCC. However, data from prospective multicenter trials are required to determine whether this strategy is universally applicable.

Abstract The SHiP-charm project was proposed to measure the associated charm production induced by 400 GeV/c protons in a thick target, including the contribution from cascade production. An optimisation run was performed in July 2018 at CERN SPS using a hybrid setup. The high resolution of nuclear emulsions acting as vertex detector was complemented by electronic detectors for kinematic measurements and muon identification. Here we present first results on the analysis of nuclear emulsions exposed in the 2018 run, which prove the capability of reconstructing proton interaction vertices in a harsh environment, where the signal is largely dominated by secondary particles produced in hadronic and electromagnetic showers within the lead target.

Purpose: The research aims to provide a structured approach for leveraging Intellectual capital (IC) to enhance sense-making within the network, ensuring clarity on the goals and stakeholders involved in each strategy. Design/methodology/approach: To tackle the research question, an exploratory analysis was conducted to investigate the Campania Oncology Network. Multiple sources of evidence were used to obtain data triangulation. Findings: We developed a taxonomy of IC-based strategies that enhance sense-making. The analysis allows the identification of the IC activities developed by Campania's Oncology Network to increase the sense of belonging to the network. The activities of health network organisations are used to identify a taxonomy of strategies to enhance sense-making. For each strategy, specific objectives and stakeholders are identified. Originality/value: This paper offers interesting practical and theoretical implications, presenting a new perspective on the role of IC in organisations.

Summary: Background and aims: A healthy diet is one of the pillars of familial hypercholesterolemia (FH) treatment. However, the best dietary pattern and indication for specific supplementation have not been established. Our aim is to conduct a pilot study to assess the effect of an adapted cardioprotective diet with or without phytosterol and/or krill oil supplement in participants with a probable or definitive diagnosis of FH, treated with moderate/high potency statins. Methods: A national, multicenter, factorial, and parallel placebo-controlled randomized clinical trial with a superiority design and 1:1:1:1 allocation rate will be conducted. The participants will undergo whole exome sequencing and be allocated into four treatment groups: 1) a cardioprotective diet adapted for FH (DICA-FH) + phytosterol placebo + krill oil placebo; 2) DICA-FH + phytosterol 2 g/day + krill oil placebo; 3) DICA-FH + phytosterol placebo + krill oil 2 g/day; or 4) DICA-FH + phytosterol 2 g/day + krill oil 2 g/day. The primary outcomes will be low-density lipoprotein (LDL)-cholesterol and lipoprotein (a) levels and adherence to treatment after a 120-day follow-up. LDL- and high-density lipoprotein (HDL)-cholesterol subclasses, untargeted lipidomics analysis, adverse events, and protocol implementation components will also be assessed. Results: A total of 58 participants were enrolled between May–August 2023. After the end of the follow-up period, the efficacy and feasibility results of this pilot study will form the basis of the design of a large-scale randomized clinical trial. Conclusions: This study's overall goal is to recommend dietary treatment strategies in the context of FH.

Colorectal cancer (CRC) is a multifaceted disease whose development and progression varies depending on tumor location, age of patients, infiltration of immune cells within cancer lesions, and the tumor microenvironment. These pathophysiological characteristics are additionally influenced by sex-related differences. The gut microbiome plays a role in initiation and progression of CRC, and shapes anti-tumor immune responses but how responsiveness of the immune system to the intestinal microbiota may contribute to sexual dimorphism of CRC is largely unknown. We studied survival, tumor-infiltrating immune cell populations and tumor-associated microbiome of a cohort of n = 184 male and female CRC patients through high-dimensional single-cell flow cytometry and 16S rRNA gene sequencing. We functionally tested the immune system-microbiome interactions in in-vivo and in-vitro models of the disease. High-dimensional single-cell flow cytometry showed that female patients are enriched by tumor-infiltrating invariant Natural Killer T (iNKT) cells but depleted by cytotoxic T lymphocytes. The enrichment of oral pathobionts and a reduction of β-glucuronidase activity are distinctive traits characterizing the gut microbiome of female patients affected by CRC. Functional assays using a collection of human primary iNKT cell lines demonstrated that the gut microbiota of female patients functionally impairs iNKT cell anti-tumor functions interfering with the granzyme-perforin cytotoxic pathway. Our results highlight a sex-dependent functional relationship between the gut microbiome, estrogen metabolism, and the decline of cytotoxic T cell responses, contributing to the sexual dimorphism observed in CRC patients with relevant implications for precision medicine and the design of targeted therapeutic approaches addressing sex bias in cancer.

The interaction between the gut microbiota and invariant Natural Killer T (iNKT) cells plays a pivotal role in colorectal cancer (CRC). The pathobiont Fusobacterium nucleatum influences the anti-tumor functions of CRC-infiltrating iNKT cells. However, the impact of other bacteria associated with CRC, like Porphyromonas gingivalis, on their activation status remains unexplored. In this study, we demonstrate that mucosa-associated P. gingivalis induces a protumour phenotype in iNKT cells, subsequently influencing the composition of mononuclear-phagocyte cells within the tumor microenvironment. Mechanistically, in vivo and in vitro experiments showed that P. gingivalis reduces the cytotoxic functions of iNKT cells, hampering the iNKT cell lytic machinery through increased expression of chitinase 3-like-1 protein (CHI3L1). Neutralization of CHI3L1 effectively restores iNKT cell cytotoxic functions suggesting a therapeutic potential to reactivate iNKT cell-mediated antitumour immunity. In conclusion, our data demonstrate how P. gingivalis accelerates CRC progression by inducing the upregulation of CHI3L1 in iNKT cells, thus impairing their cytotoxic functions and promoting host tumor immune evasion.

Background: Extracorporeal photopheresis (ECP) is considered an emerging rescue therapy for patients with chronic lung allograft dysfunction (CLAD). The aim of the study was to set up a web-based data collection tool for lung transplant patients with CLAD undergoing ECP. Methods: The web-based tool was developed using Oracle MySQL and coded in HyperText Markup Language, JavaScript and Cascading Style Sheets and was set up with pre- and post-transplant data of possible interest in CLAD. Results: The software consists of 7 major sections. The validation cohort consisted of 25 lung transplant patients (13 men and 12 women, median age at transplant 51 years). A significant improvement in the rate of decline of forced expiratory volumes in 1 second (FEV1), forced vital capacity (FVC) and FEV1/FVC after introduction of ECP was observed. Forty-four percent of patients showed a

Abstract A challenge for evolutionary developmental (evo-devo) biology is to expand the breadth of research organisms used to investigate how animal diversity has evolved through changes in embryonic development. New experimental systems should couple a relevant phylogenetic position with available molecular tools and genomic resources. As a phylum of the sister group to chordates, echinoderms extensively contributed to our knowledge of embryonic patterning, organ development and cell-type evolution. Echinoderms display a variety of larval forms with diverse shapes, making them a suitable group to compare the evolution of embryonic developmental strategies. However, because of the laboratory accessibility and the already available techniques, most studies focus on sea urchins and sea stars mainly. As a comparative approach, the field would benefit from including information on other members of this group, like the sea cucumbers (holothuroids), for which little is known on the molecular basis of their development. Here, we review the spawning and culture methods, the available morphological and molecular information, and the current state of genomic and transcriptomic resources on sea cucumbers. With the goal of making this system accessible to the broader community, we discuss how sea cucumber embryos and larvae can be a powerful system to address the open questions in evo-devo, including understanding the origins of bilaterian structures.

Abstract THOC6 variants are the genetic basis of autosomal recessive THOC6 Intellectual Disability Syndrome (TIDS). THOC6 is critical for mammalian Transcription Export complex (TREX) tetramer formation, which is composed of four six-subunit THO monomers. The TREX tetramer facilitates mammalian RNA processing, in addition to the nuclear mRNA export functions of the TREX dimer conserved through yeast. Human and mouse TIDS model systems revealed novel THOC6-dependent, species-specific TREX tetramer functions. Germline biallelic Thoc6 loss-of-function (LOF) variants result in mouse embryonic lethality. Biallelic THOC6 LOF variants reduce the binding affinity of ALYREF to THOC5 without affecting the protein expression of TREX members, implicating impaired TREX tetramer formation. Defects in RNA nuclear export functions were not detected in biallelic THOC6 LOF human neural cells. Instead, mis-splicing was detected in human and mouse neural tissue, revealing novel THOC6-mediated TREX coordination of mRNA processing. We demonstrate that THOC6 is required for key signaling pathways known to regulate the transition from proliferative to neurogenic divisions during human corticogenesis. Together, these findings implicate altered RNA processing in the developmental biology of TIDS neuropathology.

Abstract Background The occurrence of mandibular canine impaction and/ or transmigration is a rare clinical entity but diagnosis and treatment planning is of clinical significance. The associated etiological factors and the clinical guidelines for the management are still not clear. The aim of this systematic review was to summarize the available data to report the prevalence and identify the etiological factors, clinical features, and various treatment outcomes in patients with mandibular canine impaction and/or transmigration. Methods The review protocol was registered in PROSPERO (CRD42021222566) and was conducted and reported according to the PRISMA and Cochrane Handbook / Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. A computerized search of studies published up to April 30, 2023, was conducted using the following databases: Medline, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Scopus, Web of Science, and Latin American and Caribbean Health Sciences Literature. A manual search of the reference and citation lists of eligible articles and existing systematic reviews for any additions were also conducted. The Newcastle–Ottawa Scale quality assessment tool was used to assess the studies' quality. Results After removing 6 duplicates, 3700 articles were identified. For the final analysis, 19 studies published between 1985 and 2023 met all the eligibility criteria and were included. A total of 7 studies presented as good and 12 studies presented as satisfactory. Patients were screened in ten studies and diagnostic records from archives were retrieved in nine studies. The total number of diagnostic records screened was 138.394, and the total number of patients from the included studies was 43.127. Conclusions Based on the findings from this systematic review, the prevalence of mandibular canine impaction ranged from 0.008% to 1.29% while canine transmigration from 0.12% to 0.98%. Crowding of the mandibular arch, the presence of a retained deciduous canine, and odontoma or cyst are the etiological factors more commonly associated with mandibular canine impaction and or transmigration. Surgical extraction and surgical exposure followed by orthodontic traction are the two most frequently carried out treatment modalities in the management of mandibular canine impaction and or transmigration.