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Cystic fibrosis (CF)-related diabetes (CFRD), characterized by partial to complete impaired insulin secretion, is the most common extra-pulmonary complication of CF. Actually, insulin is the only approved therapy for its management. Advanced hybrid closed loop (AHCL) systems are the gold standard therapy for type 1 diabetes and have been proposed for other insulin-dependent forms of diabetes, including CFRD. With AHCL systems, people with CFRD can better manage several typical disease-related issues, such as minimal insulin requirements, its variability due to exacerbations or concomitant steroid therapies, nutritional behaviors, the co-existence of CF complications as intestinal malabsorption or liver disease. SmartGuard, the AHCL system for Medtronic Minimed 780G, requires a minimum of 8 units per day to operate. In this paper, we expose a case of two young women with CFRD with total daily insulin requirements < 8 UI, using off-label SmartGuard system over a 3 years of follow-up period, suggesting an evaluation of its use also in people with minimal insulin needs, considering its beneficial impact in glucose control and quality of life. [ABSTRACT FROM AUTHOR]

Purpose: Currently, significant medical practice variation exists in thermal ablation (TA) of malignant liver tumors with associated differences in outcomes. The IMaging and Advanced Guidance for workflow optimization in Interventional Oncology (IMAGIO) consortium aims to integrate interventional oncology into the standard clinical pathway for cancer treatment in Europe by 2030, by development of a standardized low-complex-high-precision workflow for TA of malignant liver tumors. This study was conducted at the start of the IMAGIO project with the aim to explore the current state and future role of modern technology in TA of malignant liver tumors. Materials and Methods: A cross-sectional questionnaire was conducted followed by an expert focus group discussion with core members and collaborating partners of the consortium. Results: Of the 13 participants, 10 respondents filled in the questionnaire. During the focus group discussion, there was consensus on the need for international standardization in TA and several aspects of the procedure, such as planning based on cross-sectional images, the adoption of different techniques for needle placement and the importance of needle position- and post-ablative margin confirmation scans. Yet, also considerable heterogeneity was reported in the adoption of modern technology, particularly in navigational systems and computer-assisted margin assessment. Conclusion: This study mirrored the current diversity in workflow of thermal liver ablation. To obtain comparable outcomes worldwide, standardization is needed. While advancements in tools and software hold the potential to homogenize outcome measurement and minimize operator-dependent variability, the rapid increase in availability also contributes to enhanced workflow variation. [ABSTRACT FROM AUTHOR]

Aims: It is unclear whether type 2 diabetes diagnosed in young adulthood is associated with increased severity than that occurring later in life beyond longer lifetime exposure to hyperglycemia. This study aimed at assessing the independent association of age at type 2 diabetes diagnosis with all-cause mortality. Methods: This prospective cohort study enrolled 15,773 Caucasian patients with type 2 diabetes in 19 Italian centers in 2006–2008. Cardiometabolic risk profile and presence of complications and comorbidities were assessed at baseline and participants were stratified by quartiles of age at diabetes diagnosis. All-cause mortality was verified on 31 October 2015. Results: Valid information on vital status was retrieved for 15,656 participants (99.3%). Patients in the lowest quartile had the longest diabetes duration, the worst glycemic control and the highest prevalence of insulin treatment, obesity, atherogenic dyslipidemia, and smoking habits. All complications were inversely associated with age at diabetes diagnosis after adjustment for age and sex, but not after further adjustment for diabetes duration. Percentages of death, Kaplan–Meier estimates, and unadjusted hazard ratios and mortality rates increased from the lowest to the highest quartile. In contrast, when adjusting for age and sex, participants falling in the lowest quartile, showed the highest mortality risk [hazard ratio 1.321 (95% confidence interval 1.196–1.460), P < 0.0001]. However, differences among quartiles disappeared after adjustment for diabetes duration, complications/comorbidities, or other cardiovascular risk factors. Conclusions: Type 2 diabetes onset in young adulthood is associated with increased mortality that is mainly driven by longer diabetes duration favoring the development of complications. Trial registration: ClinicalTrials.gov, NCT00715481, retrospectively registered 15 July, 2008. [ABSTRACT FROM AUTHOR]

Taking into consideration that bees can be contaminated by pesticides through the ingestion of contaminated floral resources, we can utilize genetic techniques to assess effects that are scarcely observed in behavioral studies. This study aimed to investigate the genetic effects of ingesting lethal and sublethal doses of the insecticide fipronil in foraging honey bees during two periods of acute exposure. Bees were exposed to fipronil through contaminated honey syrup at two dosages (LD50 = 0.19 µg/bee; LD50/100 = 0.0019 µg/bee) and for two durations (1 and 4 h). Following exposure, we measured syrup consumption per bee, analyzed the transcriptome of bee brain tissue, and identified differentially expressed genes (DEGs), categorizing them functionally based on gene ontology (GO). The results revealed a significant genetic response in honey bees after exposure to fipronil, regardless of the dosage used. Fipronil affected various metabolic, transport, and cellular regulation pathways, as well as detoxification processes and xenobiotic substance detection. Additionally, the downregulation of several DEGs belonging to the olfactory-binding protein (OBP) family was observed, suggesting potential physiological alterations in bees that may lead to disoriented behaviors and reduced foraging efficiency. [ABSTRACT FROM AUTHOR]

Purpose: In radioguided surgery (RGS), radiopharmaceuticals are used to generate preoperative roadmaps (e.g., PET/CT) and to facilitate intraoperative tracing of tracer avid lesions. Within RGS, there is a push toward the use of receptor-targeted radiopharmaceuticals, a trend that also has to align with the surgical move toward minimal invasive robotic surgery. Building on our initial ex vivo evaluation, this study investigates the clinical translation of a DROP-IN β probe in robotic PSMA-guided prostate cancer surgery. Methods: A clinical-grade DROP-IN β probe was developed to support the detection of PET radioisotopes (e.g., 68 Ga). The prototype was evaluated in 7 primary prostate cancer patients, having at least 1 lymph node metastases visible on PSMA-PET. Patients were scheduled for radical prostatectomy combined with extended pelvic lymph node dissection. At the beginning of surgery, patients were injected with 1.1 MBq/kg of [68Ga]Ga-PSMA. The β probe was used to trace PSMA-expressing lymph nodes in vivo. To support intraoperative decision-making, a statistical software algorithm was defined and optimized on this dataset to help the surgeon discriminate between probe signals coming from tumors and healthy tissue. Results: The DROP-IN β probe helped provide the surgeon with autonomous and highly maneuverable tracer detection. A total of 66 samples (i.e., lymph node specimens) were analyzed in vivo, of which 31 (47%) were found to be malignant. After optimization of the signal cutoff algorithm, we found a probe detection rate of 78% of the PSMA-PET-positive samples, a sensitivity of 76%, and a specificity of 93%, as compared to pathologic evaluation. Conclusion: This study shows the first-in-human use of a DROP-IN β probe, supporting the integration of β radio guidance and robotic surgery. The achieved competitive sensitivity and specificity help open the world of robotic RGS to a whole new range of radiopharmaceuticals. [ABSTRACT FROM AUTHOR]

Orientation or axial selectivity, the property of neurons in the visual system to respond preferentially to certain angles of visual stimuli, plays a pivotal role in our understanding of visual perception and information processing. This computation is performed as early as the retina, and although much work has established the cellular mechanisms of retinal orientation selectivity, how this computation is organized across the retina is unknown. Using a large dataset collected across the mouse retina, we demonstrate functional organization rules of retinal orientation selectivity. First, we identify three major functional classes of retinal cells that are orientation selective and match previous descriptions. Second, we show that one orientation is predominantly represented in the retina and that this predominant orientation changes as a function of retinal location. Third, we demonstrate that neural activity plays little role on the organization of retinal orientation selectivity. Lastly, we use in silico modeling followed by validation experiments to demonstrate that the overrepresented orientation aligns along concentric axes. These results demonstrate that, similar to direction selectivity, orientation selectivity is organized in a functional map as early as the retina. The functional organization rules of retinal orientation are not fully understood. Here the authors show that orientation detection, a crucial task for visual perception, is organized in the mouse retina along concentric axes, and that this organization develops even in the absence of visual experience or patterned spontaneous activity. [ABSTRACT FROM AUTHOR]

Evidence-based parenting interventions (EBPI) support children and families to promote resilience, address emotional and behavioral concerns, and prevent or address issues related to child maltreatment. Critiques of EBPIs include concerns about their relevance and effectiveness for diverse populations when they are implemented at population scale. Research methods that center racial equity and include community-based participatory approaches have the potential to address some of these concerns. The purpose of the present review was to document the extent to which methods associated with promoting racial equity in research have been used in studies that contribute to the evidence base for programs that meet evidentiary standards for a clearinghouse that was developed to support the Family First Prevention Services Act in the United States. We developed a coding system largely based on the Culturally Responsive Evaluation model. A sample of 47 papers that are part of the evidence base for ten in-home parent skill-based programs were reviewed and coded. Only three of 28 possible codes were observed to occur in over half of the studies (including race/ethnicity demographic characteristics, conducting measure reliability for the study sample, and including information on socioeconomic status). Although the overall presence of equity-informed methods was low, a positive trend was observed over time. This review highlights ways in which rigorous research can incorporate racial equity into the planning, design, execution, and interpretation and dissemination of programs of study. We posit that doing so improves the external validity of studies while maintaining high-quality research that can contribute to an evidence base. [ABSTRACT FROM AUTHOR]

Molecular fingerprints are indispensable tools in cheminformatics. However, stereochemistry is generally not considered, which is problematic for large molecules which are almost all chiral. Herein we report MAP4C, a chiral version of our previously reported fingerprint MAP4, which lists MinHashes computed from character strings containing the SMILES of all pairs of circular substructures up to a diameter of four bonds and the shortest topological distance between their central atoms. MAP4C includes the Cahn-Ingold-Prelog (CIP) annotation (R, S, r or s) whenever the chiral atom is the center of a circular substructure, a question mark for undefined stereocenters, and double bond cis–trans information if specified. MAP4C performs slightly better than the achiral MAP4, ECFP and AP fingerprints in non-stereoselective virtual screening benchmarks. Furthermore, MAP4C distinguishes between stereoisomers in chiral molecules from small molecule drugs to large natural products and peptides comprising thousands of diastereomers, with a degree of distinction smaller than between structural isomers and proportional to the number of chirality changes. Due to its excellent performance across diverse molecular classes and its ability to handle stereochemistry, MAP4C is recommended as a generally applicable chiral molecular fingerprint. Scientific contribution: The ability of our chiral fingerprint MAP4C to handle stereoisomers from small molecules to large natural products and peptides is unprecedented and opens the way for cheminformatics to include stereochemistry as an important molecular parameter across all fields of molecular design. [ABSTRACT FROM AUTHOR]

Achieving cost-competitive bio-based processes requires development of stable and selective biocatalysts. Their realization through in vitro enzyme characterization and engineering is mostly low throughput and labor-intensive. Therefore, strategies for increasing throughput while diminishing manual labor are gaining momentum, such as in vivo screening and evolution campaigns. Computational tools like machine learning further support enzyme engineering efforts by widening the explorable design space. Here, we propose an integrated solution to enzyme engineering challenges whereby ML-guided, automated workflows (including library generation, implementation of hypermutation systems, adapted laboratory evolution, and in vivo growth-coupled selection) could be realized to accelerate pipelines towards superior biocatalysts. Achieving cost-competitive bio-based processes requires development of stable and selective biocatalysts. In this Perspective, the authors propose an integrated solution combining growth-coupled selection with machine learning and automated workflows to accelerate development pipelines. [ABSTRACT FROM AUTHOR]

Purpose: The relationship between constitutional coronal alignment and implant positioning on trochlear groove restoration in total knee arthroplasty (TKA) is poorly understood. This study aimed to determine whether the choice of alignment philosophy significantly affects the restoration of the trochlea groove. Methods: Sixty‐one imageless robotic TKAs performed by a single orthopaedic surgeon were retrospectively reviewed. In each case, the entire native trochlea was digitized to generate the native femoral anatomy, and implants were planned according to a functional alignment (FA) technique. Final implant position was recorded using the validated bone resection planes from the navigation system. Simulated femoral component positions were generated according to previously described alignment techniques: mechanical alignment (MA), gap balancing (GB), kinematic alignment (KA), restricted kinematic alignment (rKA) and restricted inverse kinematic alignment (riKA). Trochlear angle (TA), trochlear under/overstuffing and mediolateral sulcus offset were compared between the six simulated alignment techniques, as well as the final implanted technique. Further analyses investigated the effect of preoperative coronal alignment on trochlear position. Comparisons were assessed with an analysis of variance and Welch's t‐tests or Wilcoxon's rank‐sum tests with Bonferroni corrections. Results: The implanted and simulated techniques all resulted in greater TA valgus compared to the native groove (p < 0.001). The implanted technique, KA and rKA were closer to the native TA than GB, MA and riKA (p > 0.001). All alignment philosophies understuffed the native trochlea groove. KA and rKA understuffed less than all other techniques (p < 0.001), and GB understuffed more than all other techniques (p < 0.001). In extension, all techniques shifted the trochlear sulcus laterally, while in flexion, they medialized it. These effects were most prominent in GB and MA. Conclusion: Personalized alignment techniques such as KA and rKA, which consider variations in individual anatomy, best restore the native patellar groove compared to systematic alignment techniques when using a standardized femoral component. Level of Evidence: Level III, retrospective review. [ABSTRACT FROM AUTHOR]

Hypercoagulability and reduced fibrinolysis are well-established complications associated with COVID-19. However, the timelines for the onset and resolution of these complications remain unclear. The aim of this study was to evaluate, in a cohort of COVID-19 patients, changes in coagulation and fibrinolytic activity through ROTEM assay at different time points during the initial 30 days following the onset of symptoms in both mild and severe cases. Blood samples were collected at five intervals after symptoms onset: 6–10 days, 11–15 days, 16–20 days, 21–25 days, and 26–30 days. In addition, fibrinogen, plasminogen, PAI-1, and alpha 2-antiplasmin activities were determined. Out of 85 participants, 71% had mild COVID-19. Twenty uninfected individuals were evaluated as controls. ROTEM parameters showed a hypercoagulable state among mild COVID-19 patients beginning in the second week of symptoms onset, with a trend towards reversal after the third week of symptoms. In severe COVID-19 cases, hypercoagulability was observed since the first few days of symptoms, with a tendency towards reversal after the fourth week of symptoms onset. A hypofibrinolytic state was identified in severe COVID-19 patients from early stages and persisted even after 30 days of symptoms. Elevated activity of PAI-1 and alpha 2-antiplasmin was also detected in severe COVID-19 patients. In conclusion, both mild and severe cases of COVID-19 exhibited transient hypercoagulability, reverted by the end of the first month. However, severe COVID-19 cases sustain hypofibrinolysis throughout the course of the disease, which is associated with elevated activity of fibrinolysis inhibitors. Persistent hypofibrinolysis could contribute to long COVID-19 manifestations. [ABSTRACT FROM AUTHOR]

Background: In this narrative review we aimed to explore outcomes of extracorporeal life support (extracorporeal membrane oxygenation (ECMO) and extracorporeal carbon dioxide removal (ECCO2R)) as rescue therapy in patients with status asthmaticus requiring mechanical ventilation. Methods: Multiple databases were searched for studies fulfilling inclusion criteria. Articles reporting mortality and complications of ECMO and ECCO2R in mechanically ventilated patients with acute severe asthma (ASA) were included. Pooled estimates of mortality and complications were obtained by fitting Poisson's normal modeling. Results: Six retrospective studies fulfilled inclusion criteria thus yielding a pooled mortality rate of 17% (13–20%), pooled risk of bleeding of 22% (7–37%), mechanical complications in 26% (21–31%), infection in 8% (0–21%) and pneumothorax rate 4% (2–6%). Conclusion: Our review identified a variation between institutions in the initiation of ECMO and ECCO2R in patients with status asthmaticus and discrepancy in the severity of illness at the time of cannulation. Despite that, mortality in these studies was relatively low with some studies reporting no mortality which could be attributed to selection bias. While ECMO and ECCO2R use in severe asthma patients is associated with complication risks, further studies exploring the use of ECMO and ECCO2R with mechanical ventilation are required to identify patients with favorable risk benefit ratio. [ABSTRACT FROM AUTHOR]

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Background: Conventional therapy can result in remission in mild-moderate pediatric Crohn's disease (CD). However, some patients experience loss of response to biological drugs despite increased dosage. Methods: We planned to determine that CD exclusion diet plus partial enteral nutrition offers additional benefits in asymptomatic children with CD having elevated fecal calprotectin. A randomized, open-label, pilot, controlled interventional study was conducted in children with CD while on medical treatment and elevated fecal calprotectin on routine testing. Patients continued their medications and were randomized into a group that received CD exclusion diet plus partial enteral nutrition for 12 weeks and one that continued a regular diet. Results: Twenty-one patients participated: 11 received CD exclusion diet plus partial enteral nutrition and 10, regular diet. Median fecal calprotectin in the CD exclusion diet plus partial enteral nutrition decreased in 9/11 to 50% of baseline, remaining practically unchanged in the regular diet, except for two patients (p = 0.005). Body mass index z-score increased in the CD exclusion diet plus partial enteral nutrition. Only 1/11 patients in the CD exclusion diet plus partial enteral nutrition group, while 4/10 in the regular diet, experienced clinical relapse (p = 0.149). Only one patient in the CD exclusion diet plus partial enteral nutrition, while eight in the regular diet, were considered to need their biologic treatment intensified (p = 0.005); 2/11 in the CD exclusion diet plus partial enteral nutrition had the dose or frequency of the biologic reduced vs. none (0/10) in the regular diet group. The short Pediatric Crohn's Disease Activity Index and anthropometry showed no significant changes in either group. Conclusions: Diet therapy could be a useful addition to medications in children with CD in apparent remission, but elevated fecal calprotectin. Trial registration: Clinical trial number: NCT05034458. [ABSTRACT FROM AUTHOR]

Purpose: Microwave ablation (MWA) is a treatment modality for colorectal liver metastases (CRLM). While potentially curative, more information is needed on factors that contribute to long-term local tumour control. The prospective multicentre observational study CIRSE Emprint Microwave Ablation Registry aims to prospectively collect real-world technical data and clinical outcomes on patients treated with MWA in CRLM. Methods: Eligible patients are adults with up to 9 local treatment naïve CRLM of ≤ 3 cm completely treatable with either MWA alone or MWA with resection and/or radiotherapy within 8 weeks. Data are collected, at baseline, every 3 months until 12 months, and thereafter every 6 months until the end of the study. The primary outcome measure is local tumour control. Secondary outcome measures are overall survival, (hepatic-) disease-free survival, time-to-progression untreatable by ablation, systemic therapy vacation, safety, and quality of life. Covariates related to the primary outcome measure will be assessed using a stratified log-rank test and an univariable Cox proportional hazard regression. A sample size of 500 patients with 750 lesions produces a two-sided 95% confidence interval with a precision equal to 0.057. Results: Between September 2019 and December 2022, 500 patients have been enrolled with at least 976 treated tumours. Conclusion: The prospective observational CIEMAR study will provide valuable insights into the real-world use of MWA, helping in the future patient selection and clarifying factors that may contribute to long-term local tumour control. Trial Registration: NCT03775980. [ABSTRACT FROM AUTHOR]

Purpose: The clinical outcome and the efficacy of chemotherapy in pancreatic cancer patients with BRCA1/2 Variants of Unknown Significance (VUS) is unknown. We explored the effects of chemotherapy with or without Platinum in non metastatic and metastatic pancreatic cancer patients with BRCA1/2 VUS. Methods: A retrospective analysis of non-metastatic or metastatic pancreatic cancer patients with gBRCA1/2 VUS treated in 13 Italian centers between November 2015 and December 2020 was performed. All patients were assessed for toxicity and RECIST 1.1 response. Metastatic patients were evaluated for survival outcome. Results: 30 pancreatic cancer patients with gBRCA1/2 VUS were considered: 20 were M+ and 10 were non-M+. Pl-CT was recommended to 16 patients: 10 M+ (6 FOLFIRINOX and 4 PAXG) and 6 non-M+ (3 FOLFIRINOX and 3 PAXG); 11 patients received Nabpaclitaxel-Gemcitabine (AG; 8 M+) and 3 patients (2 M+) were treated with Gemcitabine (G). The RECIST 1.1 response rate was 27% for AG and 44% for Pl-CT (22% for (m) FOLFIRINOX and 71% PAXG). 1 year Progression-Free Survival was 37.5% for patients treated with AG and 33% in the Pl-CT subgroup. Median Overall Survival (OS) was 23.5 months for patients treated with AG and 14 months for the Pl-CT subgroup. 1 Year and 2 Year OS were numerically better for AG (1 Year OS: 75% vs 60% and 2 Year OS: 50% and 20% in AG and Pl-CT subgroups, respectively) as well. Conclusions: Pl-CT does not seem to be associated with a better outcome compared to AG chemotherapy in PDAC patients with BRCA 1/2 VUS. [ABSTRACT FROM AUTHOR]

Objective: Breast magnetic resonance imaging (MRI) and contrast-enhanced mammography (CEM) are nowadays used in breast imaging but studies about their inter-reader agreement are lacking. Therefore, we compared the inter-reader agreement of CEM and MRI in breast cancer diagnosis in the same patients. Methods: Breast MRI and CEM exams performed in a single center (09/2020–09/2021) for an IRB-approved study were retrospectively and independently evaluated by four radiologists of two different centers with different levels of experience who were blinded to the clinical and other imaging data. The reference standard was the histological diagnosis or at least 1-year negative imaging follow-up. Inter-reader agreement was examined using Cohen's and Fleiss' kappa (κ) statistics and compared with the Wald test. Results: Of the 750 patients, 395 met inclusion criteria (44.5 ± 14 years old), with 752 breasts available for CEM and MRI. Overall agreement was moderate (κ = 0.60) for MRI and substantial (κ = 0.74) for CEM. For expert readers, the agreement was substantial (κ = 0.77) for MRI and almost perfect (κ = 0.82) for CEM; for non-expert readers was fair (κ = 0.39); and for MRI and moderate (κ = 0.57) for CEM. Pairwise agreement between expert readers and non-expert readers was moderate (κ = 0.50) for breast MRI and substantial (κ = 0.74) for CEM and it showed a statistically superior agreement of the expert over the non-expert readers only for MRI (p = 0.011) and not for CEM (p = 0.062). Conclusions: The agreement of CEM was superior to that of MRI (p = 0.012), including for both expert (p = 0.031) and non-expert readers (p = 0.005). [ABSTRACT FROM AUTHOR]

A true circular carbon economy must upgrade waste greenhouse gases. C1-based biomanufacturing is an attractive solution, in which one carbon (C1) molecules (e.g. CO2, formate, methanol, etc.) are converted by microbial cell factories into value-added goods (i.e. food, feed, and chemicals). To render C1-based biomanufacturing cost-competitive, we must adapt microbial metabolism to perform chemical conversions at high rates and yields. To this end, the biotechnology community has undertaken two (seemingly opposing) paths: optimizing natural C1-trophic microorganisms versus engineering synthetic C1-assimilation de novo in model microorganisms. Here, we pose how these approaches can instead create synergies for strengthening the competitiveness of C1-based biomanufacturing as a whole. Using one carbon (C1) molecules as primary feedstock for bioproduction holds great potential for a circular and carbon neutral economy. Here, the authors discuss the potential of merging knowledge gained from natural and synthetic C1-trophic organisms to expedite the development of efficient C1-based biomanufacturing. [ABSTRACT FROM AUTHOR]

Objectives: The study aim was to conduct a systematic review of the literature reporting the application of radiomics to imaging techniques in patients with ovarian lesions. Methods: MEDLINE/PubMed, Web of Science, Scopus, EMBASE, Ovid and ClinicalTrials.gov were searched for relevant articles. Using PRISMA criteria, data were extracted from short-listed studies. Validity and bias were assessed independently by 2 researchers in consensus using the Quality in Prognosis Studies (QUIPS) tool. Radiomic Quality Score (RQS) was utilised to assess radiomic methodology. Results: After duplicate removal, 63 articles were identified, of which 33 were eligible. Fifteen assessed lesion classifications, 10 treatment outcomes, 5 outcome predictions, 2 metastatic disease predictions and 1 classification/outcome prediction. The sample size ranged from 28 to 501 patients. Twelve studies investigated CT, 11 MRI, 4 ultrasound and 1 FDG PET-CT. Twenty-three studies (70%) incorporated 3D segmentation. Various modelling methods were used, most commonly LASSO (least absolute shrinkage and selection operator) (10/33). Five studies (15%) compared radiomic models to radiologist interpretation, all demonstrating superior performance. Only 6 studies (18%) included external validation. Five studies (15%) had a low overall risk of bias, 9 (27%) moderate, and 19 (58%) high risk of bias. The highest RQS achieved was 61.1%, and the lowest was − 16.7%. Conclusion: Radiomics has the potential as a clinical diagnostic tool in patients with ovarian masses and may allow better lesion stratification, guiding more personalised patient care in the future. Standardisation of the feature extraction methodology, larger and more diverse patient cohorts and real-world evaluation is required before clinical translation. Clinical relevance statement: Radiomics shows promising results in improving lesion stratification, treatment selection and outcome prediction. Modelling with larger cohorts and real-world evaluation is required before clinical translation. Key points: • Radiomics is emerging as a tool for enhancing clinical decisions in patients with ovarian masses. • Radiomics shows promising results in improving lesion stratification, treatment selection and outcome prediction. • Modelling with larger cohorts and real-world evaluation is required before clinical translation. [ABSTRACT FROM AUTHOR]

This study evaluates the quality of published research using artificial intelligence (AI) for ovarian cancer diagnosis or prognosis using histopathology data. A systematic search of PubMed, Scopus, Web of Science, Cochrane CENTRAL, and WHO-ICTRP was conducted up to May 19, 2023. Inclusion criteria required that AI was used for prognostic or diagnostic inferences in human ovarian cancer histopathology images. Risk of bias was assessed using PROBAST. Information about each model was tabulated and summary statistics were reported. The study was registered on PROSPERO (CRD42022334730) and PRISMA 2020 reporting guidelines were followed. Searches identified 1573 records, of which 45 were eligible for inclusion. These studies contained 80 models of interest, including 37 diagnostic models, 22 prognostic models, and 21 other diagnostically relevant models. Common tasks included treatment response prediction (11/80), malignancy status classification (10/80), stain quantification (9/80), and histological subtyping (7/80). Models were developed using 1–1375 histopathology slides from 1–776 ovarian cancer patients. A high or unclear risk of bias was found in all studies, most frequently due to limited analysis and incomplete reporting regarding participant recruitment. Limited research has been conducted on the application of AI to histopathology images for diagnostic or prognostic purposes in ovarian cancer, and none of the models have been demonstrated to be ready for real-world implementation. Key aspects to accelerate clinical translation include transparent and comprehensive reporting of data provenance and modelling approaches, and improved quantitative evaluation using cross-validation and external validations. This work was funded by the Engineering and Physical Sciences Research Council. [ABSTRACT FROM AUTHOR]

Inflammatory phenomena have a direct impact on the prognosis of orthotopic liver transplantation (OLT). Neutrophil extracellular traps (NETs) contribute to OLT inflammation and hemostasis imbalance in OLT. The association between NETosis, clinical outcomes and transfusion requirements is not determined. To evaluate NETs release during OLT and the effect of NETosis ontransfusion requirements and adverse outcomes in a prospective cohort of patients submitted to OLT. We quantified citrullinated histones (cit-H3) and circulating-free-DNA (cf-DNA) in ninety-three patients submitted to OLT in three periods: pre-transplant, after graft reperfusion and before discharge. NETs markers were compared between these periods using ANOVA test. The association of NETosis and adverse outcomes was evaluated using regression models adjusted for age, sex and corrected MELD. We observed a peak of circulating NETs following reperfusion, evidenced by a 2.4-fold increase in cit-H3 levels in the post-graft reperfusion period (median levels of cit-H3 pre transplant: 0.5 ng/mL, after reperfusion: 1.2 ng/mL and at discharge 0.5 ng/mL, p < 0.0001). We observed an association between increased levels of cit-H3 and in-hospital death (OR = 1.168, 95% CI 1.021–1.336, p = 0.024). No association was found between NETs markers and transfusion requirements. There is a prompt release of NETs after reperfusion that is associated with poorer outcomes and death. Intraoperative NETs release seems to be independent of transfusion requirements. These findings highlight the relevance of inflammation promoted by NETS and its impact on OLT adverse clinical outcomes. [ABSTRACT FROM AUTHOR]

Spermiogenesis is a radical process of differentiation whereby sperm cells acquire a compact and specialized morphology to cope with the constraints of sexual reproduction while preserving their main cargo, an intact copy of the paternal genome. In animals, this often involves the replacement of most histones by sperm-specific nuclear basic proteins (SNBPs). Yet, how the SNBP-structured genome achieves compaction and accommodates shaping remain largely unknown. Here, we exploit confocal, electron and super-resolution microscopy, coupled with polymer modeling to identify the higher-order architecture of sperm chromatin in the needle-shaped nucleus of the emerging model cricket Gryllus bimaculatus. Accompanying spermatid differentiation, the SNBP-based genome is strikingly reorganized as ~25nm-thick fibers orderly coiled along the elongated nucleus axis. This chromatin spool is further found to achieve large-scale helical twisting in the final stages of spermiogenesis, favoring its ultracompaction. We reveal that these dramatic transitions may be recapitulated by a surprisingly simple biophysical principle based on a nucleated rigidification of chromatin linked to the histone-to-SNBP transition within a confined nuclear space. Our work highlights a unique, liquid crystal-like mode of higher-order genome organization in ultracompact cricket sperm, and establishes a multidisciplinary methodological framework to explore the diversity of non-canonical modes of DNA organization. Orsi et al. identify an elegant solution to DNA packing in cricket sperm nuclei, whereby relatively simple biophysical changes in chromatin properties result in a liquid crystal-like twisted spool organization that favors ultracompaction. [ABSTRACT FROM AUTHOR]

Background: Current breast implant prevalence within the general population remains elusive. An accurate prevalence is critical to serve as the denominator for any assessment of breast implant-related complication. The purpose of this manuscript is to assess this prevalence in women aged 20–70 years in Italy. Materials and Methods: Eight reviewers, demonstrating a mean sensitivity of 87.0% and specificity of 97.0%, were recruited for retrospective identification of implants on chest radiographs from a tertiary academic hospital in a major urban setting. Three final reviewers were selected, and they assessed all eligible chest radiographs collected between January and December 2019. The hospital-based population was compared to epidemiological data at a local, regional and national level to demonstrate homogeneity of age structures using the phi correlation coefficient. Results: We identified 3,448 chest X-rays which yielded 140 implants, with an overall prevalence of 4.1% for women aged 20–70. Implants were bilateral in 76% of cases and unilateral in 24%. They were placed cosmetically in 47.1% cases and used for reconstruction in 52.9% cases. Phi correlation coefficient found no differences across hospital-based, local, regional and national populations. Conclusion: A validated method was performed to estimate implant prevalence from an academic hospital in a major urban setting at 4.1% and was used to estimate national prevalence in Italy. The implications of this epidemiologic study may reach across national borders for improved understanding of breast implant epidemiology and in predicting the total number of patients within a given population that may be affected by device complications. Level of Evidence IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. [ABSTRACT FROM AUTHOR]

Monoclonal gammopathy of undetermined significance (MGUS) is a plasma cell disorder that can precede the diagnosis of multiple myeloma. MGUS is characterized by the presence of a monoclonal paraprotein without evidence of multiple myeloma or other lymphoplasmacytic malignancies. Even though MGUS is an asymptomatic condition that does not require management strategies other than periodic follow-up to prevent complications, secondary nonmalignant diseases may arise, requiring control of the plasma cell clone. Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder that occurs in patients with no prior personal or family history of bleeding. It is associated with several other disorders, such as neoplasia, mainly hematological (including MGUS and other lymphoproliferative disorders), autoimmune, infectious and cardiac diseases. At diagnosis, patients usually present with cutaneous and mucosal bleeding, including gastrointestinal bleeding. Here, we report a case of a patient with MGUS who developed AVWS after one year of follow-up. The patient was refractory to glucocorticoids and cyclophosphamide and achieved remission only after monoclonal paraprotein was eradicated following treatment with bortezomib and dexamethasone. Our report sdemonstrates that, for refractory cases, eradication of the monoclonal paraprotein may be necessary to treat bleeding complications due to MGUS-associated AVWS. [ABSTRACT FROM AUTHOR]

Purpose: Objectives are (1) to evaluate the biomechanical effect of isolated medial patellofemoral ligament (MPFL) reconstruction in the setting of increased tibial tuberosity–trochlear groove distance (TTTG), in terms of patella contact pressures, contact area and lateral displacement; (2) to describe the threshold of TTTG up to which MPFL reconstruction should be performed alone or in combination with tibial tuberosity transfer. Methods: A finite element model of the knee was developed and validated. The model was modified to simulate isolated MPFL reconstruction, tibial tuberosity transfer and MPFL reconstruction combined with tibial tuberosity transfer for patella malalignment. Two TT–TG distances (17 mm and 22 mm) were simulated. Patella contact pressure, contact area and lateral displacement were analysed. Results: Isolated MPFL reconstruction, at early degrees of flexion, restored normal patella contact pressure when TTTG was 17 mm, but not when TTTG was 22 mm. After 60° of flexion, the TTTG distance was the main factor influencing contact pressure. Isolated MPFL reconstruction for both TTTG 17 mm and 22 mm showed higher contact area and lower lateral displacement than normal throughout knee flexion. Tibial tuberosity transfer, at early degrees of flexion, reduced the contact pressure, but did not restore the normal contact pressure. After 60° of flexion, the TTTG distance was the main factor influencing contact pressure. Tibial tuberosity transfer maintained lower contact area than normal throughout knee flexion. The lateral displacement was higher than normal between 0° and 30° of flexion (< 0.5 mm). MPFL reconstruction combined with tibial tuberosity transfer produced the same contact mechanics and kinematics of the normal condition. Conclusion: This study highlights the importance of considering to correct alignment in lateral tracking patella to avoid focal patella overload. Our results showed that isolated MPFL reconstruction corrects patella kinematics regardless of TTTG distance. However, isolated MPFL reconstruction would not restore normal patella contact pressure when TTTG is 22 mm. For TTTG 22 mm, the combined procedure of MPFL reconstruction and tibial tuberosity transfer provided an adequate patellofemoral contact mechanics and kinematics, restoring normal biomechanics. This data supports the use of MPFL reconstruction when the patient has normal alignment and the use of combined MPFL reconstruction and tibial tuberosity transfer in patients with elevated TT–TG distances to avoid focal overload. [ABSTRACT FROM AUTHOR]

Middle cerebral artery occlusion (MCAO) models show substantial variability in outcome, introducing uncertainties in the evaluation of treatment effects. Early outcome predictors would be essential for prognostic purposes and variability control. We aimed to compare apparent diffusion coefficient (ADC) MRI data obtained during MCAO and shortly after reperfusion for their potentials in acute-phase outcome prediction. Fifty-nine male rats underwent a 45-min MCAO. Outcome was defined in three ways: 21-day survival; 24 h midline-shift and neurological scores. Animals were divided into two groups: rats surviving 21 days after MCAO (survival group, n = 46) and rats dying prematurely (non-survival/NS group, n = 13). At reperfusion, NS group showed considerably larger lesion volume and lower mean ADC of the initial lesion site (p < 0.0001), while during occlusion there were no significant group differences. At reperfusion, each survival animal showed decreased lesion volume and increased mean ADC of the initial lesion site compared to those during occlusion (p < 10–6), while NS group showed a mixed pattern. At reperfusion, lesion volume and mean ADC of the initial lesion site were significantly associated with 24 h midline-shift and neurological scores. Diffusion MRI performed soon after reperfusion has a great impact in early-phase outcome prediction, and it works better than the measurement during occlusion. [ABSTRACT FROM AUTHOR]

Background: Pancreatic ductal adenocarcinoma (PDAC) harbouring germline BRCA1-2 pathogenic variants (gBRCA1-2pv) is a distinct nosological entity. Information on second-line therapy (2LT) outcome in this setting is lacking. Methods: Data of gBRCA1-2pv metastatic PDAC patients treated with chemotherapy were collected. A primary analysis of 2LT RECIST response, median progression-free survival (mPFS2) and overall survival (mOS2), was performed. A secondary analysis addressed the impact of timing of platinum introduction on the outcome of patients receiving at least a first-line combination chemotherapy (1LT). Results: Eighty-four gBRCA1-2pv metastatic PDAC patients were enrolled. The primary analysis, including 43 patients, highlighted a significant improvement of mPFS2 and a doubled response rate, in the platinum-based 2LT subgroup as compared to the platinum-free (8.8 versus 3.7 months, p = 0.013). Seventy-seven patients were included in the secondary analysis. Median PFS1 of 3- and 4-drug platinum-based 1LT significantly outperformed both platinum-free combinations and platinum-based doublets (11.4 versus 6.4 versus 7.9 months, p = 0.01). Albeit still immature, data on mOS paralleled those on mPFS. Conclusions: This study highlighted the beneficial role of platinum agents in gBRCA1-2pv PDAC patients also in second-line treatment setting. However, our data suggest that early use of 3- and 4-drug platinum-based chemotherapy combinations provides a survival outcome advantage. [ABSTRACT FROM AUTHOR]

Compassion is a key quality in palliative care; however, there is a lack of evidence of the need to discuss the theme of compassion and professionals' training in the subject. The study aimed to investigate the knowledge of the construct of a sample of Italian healthcare professionals (HCPs) working in palliative care. In addition, their learning needs and training opportunities were explored. An online survey was completed by 330 HCPs. It was divided into five sections which examined knowledge of the construct of compassion and the perception of its utility in palliative care, the activities carried out in eventual training in compassion, and professionals' learning needs thereof. Professionals who had knowledge of the right definition of compassion considered it more useful and training more necessary. Most of the sample never received training about compassion. However, 97% of those who received training believed it to be necessary. Satisfaction with training was higher among those who received multidisciplinary team education. Training occasions are relatively rare in the Italian context, although they seem to increase knowledge and awareness about the construct utility and training necessity. Besides, multidisciplinary team training seems to be more satisfying. Offering team training on compassion can promote a deeper awareness of it and of its utility in clinical practice. [ABSTRACT FROM AUTHOR]

Land take, namely the conversion of natural land into impervious surfaces, is partly driven by path dependency, whereby dispersed settlements tend to spread more than compact ones over time. Yet there is limited knowledge about the extent to which specific aspects of compactness are associated with land take: a link that is instead crucial to formulate effective policies. This study investigates the impact of density, centrality, contiguity and degree of imperviousness by regressing land take data from 100 Italian NUTS3 administrative units for the period 2006–2012 against measures of the above-mentioned aspects as of 2006. Results indicate that higher shares of people in the 2000–2500 people km−2 density class, greater proximity of the population to urban centres, more contiguous urbanization patterns all help contain land take over time, whereas no significant effect was found for imperviousness. Increasing distance from protected areas reduces the positive effect of having more people live at densities of 2000–3000 people km−2, while steeper slopes enhance such effect. Planning interventions aimed at raising the share of people living at densities of 2000–2500 people km−2 as well as improving the degree of centrality or contiguity of urbanization patterns can lead to a decline in land take (measured as area of new land take per unit area of current land take) over a 6-year time span comprised between around 6 and 35% depending on location. Further research is needed to confirm the validity of our results and explore the feasibility of such interventions. [ABSTRACT FROM AUTHOR]

Growing literature indicates that problematic Internet use (PIU) and excessive smartphone use (ESU) are associated with breakdown of functional brain networks. The effects of PIU&ESU on emotional face expression (EFE) recognition are not well understood, however behavioural investigations and fMRI studies of different addiction forms indicated the impairment of this function. The Facial Emotion Recognition Paradigm was used to probe cortico-limbic responses during EFE recognition. Combined fMRI and psychophysiological analysis were implemented to measure EFE-related functional brain changes in PIU&ESU. Self-reported questionnaires were used to assess PIU&ESU. Positive associations were found between the extent of PIU&ESU and functional connections related to emotional cognitive control and social brain networks. Our findings highlight the involvement of social functioning, especially EFE recognition in PIU&ESU. Therefore, we emphasize that besides the brain's executive and reward systems, the social brain network might be the next candidate to be involved in the pathogenesis of PIU&ESU. [ABSTRACT FROM AUTHOR]

Solid line represents the survival function and dashed lines represent the lower and upper 95% confidence interval After a new treatment was started, twelve out of 38 patients (31.6%) sustained response with only one line of treatment, and seven (18.4%) patients required two lines of treatment to sustain the response. Of the entire cohort of 87 patients, 38 patients needed new ITP therapy after splenectomy; the 5-year treatment-free survival is shown in Fig. The types of infections were pneumonia (one patient), bloodstream infection due to I E. coli i (one patient), and fever of unknown origin (one patient). Dear Editor, Immune thrombocytopenia (ITP) is characterized by isolated platelet count less than 100 × 10 SP 9 sp /L in the absence of other causes of thrombocytopenia [[1]]. [Extracted from the article]

We analyzed the changes in the gene expression of forage honey bees (Apis mellifera) exposed to fipronil field-relevant dose (2.5 ppb/bee) by 1 or 4 h. A reduction in the expression of nine genes was observed after 4 h of exposure, five of which are related to the digestive system: endoglucanase E-4, MSS11 transcription activator, inositol monophosphatase 2-X1 transcription variant, ATP-binding cassette G subfamily, and cuticular protein 28; one related to exoskeleton composition: cuticular protein 28; two related to vitamin E transport and antioxidant system: alpha-tocopherol transfer protein-like and transcript variant X3. LOC551765, LOC100578929, and LOC102656070 were downregulated; however, these genes have not yet been studied. The results indicate that the fipronil causes changes in the expression of genes related to physiological and morphological, metabolism, and behavior in A. mellifera honey bees. [ABSTRACT FROM AUTHOR]

Impairment of moment-to-moment adjustment of cerebral blood flow (CBF) to the increased oxygen and energy requirements of active brain regions via neurovascular coupling (NVC) contributes to the genesis of age-related cognitive impairment. Aging is associated with marked deficiency in the vasoprotective hormone insulin-like growth factor-1 (IGF-1). Preclinical studies on animal models of aging suggest that circulating IGF-1 deficiency is causally linked to impairment of NVC responses. The present study was designed to test the hypotheses that decreases in circulating IGF-1 levels in older adults also predict the magnitude of age-related decline of NVC responses. In a single-center cross-sectional study, we enrolled healthy young (n = 31, 11 female, 20 male, mean age: 28.4 + / − 4.2 years) and aged volunteers (n = 32, 18 female, 14 male, mean age: 67.9 + / − 4.1 years). Serum IGF-1 level, basal CBF (phase contrast magnetic resonance imaging (MRI)), and NVC responses during the trail making task (with transcranial Doppler sonography) were assessed. We found that circulating IGF-1 levels were significantly decreased with age and associated with decreased basal CBF. Age-related decline in IGF-1 levels predicted the magnitude of age-related decline in NVC responses. In conclusion, our study provides additional evidence in support of the concept that age-related circulating IGF-1 deficiency contributes to neurovascular aging, impairing CBF and functional hyperemia in older adults. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this systematic review was to investigate the clinical effectiveness of glass ionomer cements (GICs) compared to other restorative materials in the treatment of radiation-related caries.Methods: Two independent researchers searched literature databases (PubMed, Scopus, Web of Science, Cochrane Library, Lilacs/BBO) and the grey literature to identify clinical trials that compared GICs with other restorative materials for the treatment of radiation-related caries. The clinical criteria considered for the performance of the restorations were based on the parameters of marginal adaptation/anatomical form, secondary caries, retention, and cumulative failures of the restorations. The methodological quality and risk of bias were evaluated using the Cochrane Collaboration tool.Results: From a total of 511, only four articles fulfilled the inclusion criteria. Conventional GIC restorations presented higher marginal adaptation failures than the resin-modified glass ionomer cements (RM-GICs) and composite restorations in all of the follow-up periods. Secondary caries was not observed in conventional GIC restorations throughout the follow-up periods, in three out of four of the included studies. RM-GICs and composite restorations showed significantly lower cumulative failure rates than conventional GICs at 6-, 12-, and 18-month follow-ups.Conclusion: Due to insufficient scientific evidence, it was not possible to conclude that GICs are more effective than other restorative materials for the treatment of radiation-related caries. [ABSTRACT FROM AUTHOR]

Aims: The 2019 and 2021 European Society of Cardiology (ESC) classifications stratified patients with type 2 diabetes into three categories according to the 10-year risk of death from atherosclerotic cardiovascular disease (ASCVD). The very high-risk category included individuals with established ASCVD, target organ damage (TOD), and/or, in the 2019 classification only, ≥ 3 additional ASCVD risk factors. We assessed risk of all-cause mortality according to the two ESC classifications in the Renal Insufficiency And Cardiovascular Events cohort. Methods: Participants (n = 15,773) were stratified based on the presence of ASCVD, TOD, and ASCVD risk factors at baseline (2006–2008). Vital status was retrieved in 2015. Results: Less than 1% of participants fell in the moderate-risk category. According to the 2019 classification, ~ 1/3 fell in the high-risk and ~ 2/3 in the very high-risk category, whereas the opposite occurred with the 2021 classification. Mortality risk increased across categories according to both classifications. Among very high-risk patients, mortality was much lower in those with ≥ 3 additional ASCVD risk factors and almost equal in those with TOD and ASCVD ± TOD, using the 2019 classification, whereas it was much higher in those with ASCVD + TOD and, to a lesser extent, TOD only than in those with ASCVD only, using the 2021 classification. Conclusions: The negligible number of moderate-risk patients suggests that these classifications might overestimate risk of ASCVD death. Downgrading patients with ≥ 3 additional ASCVD risk factors to the high-risk category is consistent with mortality data. Risk of death is very high in the presence of TOD irrespective of established ASCVD. Trial registration: ClinicalTrials.gov, NCT00715481. [ABSTRACT FROM AUTHOR]

Hatchery fish stocking is one of the main actions adopted as a form of conservation and replacement of fishing stocks. Under Brazilian law, the release of fish has become mandatory and is seen as one of the main ways of mitigating the negative effects on fish populations and preserving the ichthyofauna. Since its institution, the efficiency of this method has been questioned by the Brazilian scientific community, due to the lack of monitoring based on scientific criteria. The objective of this work was to discuss the few available reports and to analyze their deficiencies and analyze the real risks and/or benefits arising from the methodologies employed in hatchery stocking activities developed in Brazil. For this, three different studies developed in the Paranapanema River, Southeast/South of Brazil, were evaluated seeking evidence of the efficiency or inefficiency of these actions, such as management of the conservation of fish species and stocks. Our analysis shows that this management policy is poorly evaluated, and review of the planning of the stocking programs is essential, in order to improve, update, modernize, and unify the knowledge of the producing stations with respect to the existing ecological and genetic studies, aiming at better monitoring and greater effectiveness in the results advance. Also, a protocol is suggested to standardize and guide new conservationist policies of hatchery fish stocking. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to compare ligament balance and laxity profiles achieved throughout flexion in restricted kinematic alignment (rKA) and gap balancing (GB). rKA and GB both aim to improve soft tissue balance and reduce ligament releases in total knee arthroplasty (TKA). Methods: One surgeon performed 68 rKA, another performed 73 GB TKAs using the same CR implant and robotic system. rKA limited femoral valgus and tibial varus to 6°, with tibial recuts performed to achieve balance. GB limited tibial varus and femoral valgus to 2°, with femoral resections adjusted to achieve mediolateral balance throughout flexion using predictive-gap planning software. Final joint laxity was measured using a robotic ligament tensioner. Statistical analyses were performed to compare differences in mediolateral balance and joint laxity throughout flexion. Further analyses compared alignment, joint line elevation and orientation (JLO), and frequency of ligament releases and bone recuts. Results: Both techniques reported greater lateral laxity throughout flexion, with GB reporting improved mediolateral balance from 10° to 45° flexion. GB resected 1.7 mm more distal femur (p ≤ 0.001) and had greater overall laxity than rKA throughout flexion (p ≤ 0.01). rKA increased JLO by 2.5° and 3° on the femur and tibia (p ≤ 0.001). Pre-operative and post-operative coronal alignment were similar across both techniques. rKA had a higher tibial recut rate: 26.5% vs 1.4%, p < 0.001. Conclusions: rKA and GB both report lateral laxity but with different JLO and elevation. Use of a predictive-gap GB workflow resulted in greater mediolateral gap symmetry with fewer recuts. Level of evidence: III, retrospective cohort study. [ABSTRACT FROM AUTHOR]

The explanatory objection against the fitting attitude account of value states that if the properties of attitudes explain fittingness facts, but do not always explain value facts, then value facts cannot be identical with or reduced to fittingness facts. One reply to this objection is to claim that the constitutive properties of attitudes also explain value facts, for they are enablers for the value possessed by an object (the "enabling maneuver"). In this paper we argue that the enabling maneuver exposes FA to a new explanatory objection, to the extent that the explanatory role played by the constitutive properties of attitudes in value facts is assumed to be different from the explanatory role they play in fittingness facts. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effective spread of image-guided thermal ablation in thyroid gland and to characterize its current perceptions among European interventional radiologists.Materials and Methods: A questionnaire with 29 multiple choice questions about thyroid ablation was sent as an E-blast to 4752 CIRSE members. Only those who completed the survey in all its parts were included in the study.Results: 242/4752 (5.09%) participants (212 males and 30 females) completed and submitted the survey. A total of 160 subjects (66.1%) were familiar with any image-guided thermal ablations, but only 63 (26% of total population) usually perform thermal ablation for thyroid gland. Only 19.5% of the interviewed sample treats micropapillary thyroid tumours and the vast majority routinely uses radiofrequency ablation (84.4%).Conclusion: There is a significant mismatch between thyroid ablation as reported by the literature and the relatively low percentage of interventional radiology actively performing such procedure in Europe. A considerable effort is required by the Cardiovascular and Interventional Radiological Society of Europe to fill this lack. [ABSTRACT FROM AUTHOR]

The neurodegenerative condition FENIB (familiar encephalopathy with neuroserpin inclusion bodies) is caused by heterozygous expression of polymerogenic mutant neuroserpin (NS), with polymer deposition within the endoplasmic reticulum (ER) of neurons. We generated transgenic neural progenitor cells (NPCs) from mouse fetal cerebral cortex stably expressing either the control protein GFP or human wild type, polymerogenic G392E or truncated (delta) NS. This cellular model makes it possible to study the toxicity of polymerogenic NS in the appropriated cell type by in vitro differentiation to neurons. Our previous work showed that expression of G392E NS in differentiated NPCs induced an adaptive response through the upregulation of several genes involved in the defence against oxidative stress, and that pharmacological reduction of the antioxidant defences by drug treatments rendered G392E NS neurons more susceptible to apoptosis than control neurons. In this study, we assessed mitochondrial distribution and found a higher percentage of perinuclear localisation in G392E NS neurons, particularly in those containing polymers, a phenotype that was enhanced by glutathione chelation and rescued by antioxidant molecules. Mitochondrial membrane potential and contact sites between mitochondria and the ER were reduced in neurons expressing the G392E mutation. These alterations were associated with a pattern of ER stress that involved the ER overload response but not the unfolded protein response. Our results suggest that intracellular accumulation of NS polymers affects the interaction between the ER and mitochondria, causing mitochondrial alterations that contribute to the neuronal degeneration seen in FENIB patients. [ABSTRACT FROM AUTHOR]

An elevated risk of myeloma precursor disease, monoclonal gammopathy of undetermined significance (MGUS), was identified among Fire Department of the City of New York (FDNY) World Trade Center (WTC)-exposed firefighters. Further investigation was needed to determine if these findings were reproducible in a more heterogeneous WTC-exposed rescue/recovery workers cohort, the Stony Brook University-General Responder Cohort GRC (SBU-GRC). MGUS risk was compared between the cohorts and to published general population estimates from Olmsted County, MN, USA. In this observational seroprevalence study, odds ratios (OR) and age-standardized risk ratios (RR) of MGUS (M-spike and light-chain-MGUS combined), M-spike, and light-chain-MGUS were estimated using logistic regression. Age-standardized prevalences were calculated for white males aged 50–79; RRs were estimated by comparing risk in the WTC-exposed cohort with the Olmsted County screened cohort. SBU-GRC had elevated odds of MGUS compared with FDNY (OR = 1.38; 95%CI = 1.00–1.89). The age-standardized prevalence of MGUS was 9.0/100 persons (95%CI = 7.5–10.6), over two-fold higher than the general population (RR = 2.08; 95%CI = 1.72–2.51); the age-standardized prevalence of light-chain-MGUS was 3.5-fold higher (RR = 3.54; 95%CI = 2.52–4.97). This study adds to mounting evidence supporting an association between WTC/environmental exposures and MGUS among rescue/recovery workers. Access to MGUS screenings for the entire WTC-exposed cohort could allow for treatment interventions that improve survival. [ABSTRACT FROM AUTHOR]

Neurologic and psychiatric symptoms have been reported in the months following the infection with COVID-19. A low-grade inflammation has been associated both with depression and cognitive symptoms, suggesting a link between these disorders. The aim of the study is to investigate cognitive functioning 6 months following hospital discharge for COVID-19, the impact of depression, and the consequences on quality of life. Ninety-two COVID-19 survivors evaluated at 1-month follow-up, 122 evaluated at 3 months and 98 evaluated at 6 months performed neuropsychological and psychiatric evaluations and were compared with a healthy comparison group (HC) of 165 subjects and 165 patients with major depression (MDD). Cognitive performances were adjusted for age, sex, and education. Seventy-nine percent of COVID-19 survivors at 1 month and 75% at 3- and 6-month follow-up showed cognitive impairment in at least one cognitive function. No significant difference in cognitive performances was observed between 1-, 3-, and 6-months follow-up. COVID-19 patients performed worse than HC but better than MDD in psychomotor coordination and speed of information processing. No difference between COVID-19 survivors and MDD was observed for verbal fluency, and executive functions, which were lower than in HC. Finally, COVID-19 survivors performed the same as HC in working memory and verbal memory. The factor that most affected cognitive performance was depressive psychopathology which, in turn, interact with cognitive functions in determining quality of life. Our results confirm that COVID-19 sequelae include signs of cognitive impairment which persist up to 6 months after hospital discharge and affect quality of life. [ABSTRACT FROM AUTHOR]

Purpose: To estimate the prevalence of Metabolic Syndrome (MetS) and its association with changes in modifiable risk factors in older adults from southern Brazil. Methods: A longitudinal study was performed with data from EpiFloripa Aging study. We defined MetS by the existence of three or more of the following risk factors for cardiovascular disease (CVD): waist circumference (WC) (≥ 92 cm in men and ≥ 87 cm in women); fasting glucose (≥100 mg/dl); decreased HDL cholesterol (<40 mg/dl in men and <50 mg/dl in women); hypertriglyceridemia (≥150 mg/dl) and blood pressure (≥130/85 mmHg). We evaluated the changes in modifiable risk factors (smoking, alcohol consumption, fruit and vegetable consumption, physical activity, and body mass index) between the two moments of the study (2009/10 and 2013/14). Directed acyclic graph and logistic regression models were used. Results: Among the 599 participants, the prevalence of MetS was 64.0% (95% CI, 58.7–68.9). In the adjusted analysis, those who remained or became persons who are overweight (OR = 4.59; 95% CI: 3.05–6.89) and those who remained or became insufficiently active (OR = 1.92; 95% CI: 1.23–2.98) were more likely to present MetS. Conclusion: Our findings suggest that being or becoming overweight and being or becoming insufficiently active are modifiable factors associated with MetS. These results highlight the need for developing preventive strategies for the observed risk indicators to mitigate the prevalence of MetS in older adults. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate survival outcomes and safety after chemoembolization using irinotecan-loaded small-size beads (DEB-IRI) in patients with colorectal liver metastases unresponsive to standard chemotherapy. Materials and methods: Between December 2013 and August 2019, fifty-five patients (32 males, median age 64.5 years) with pretreated colorectal liver metastases unresponsive to standard chemotherapy underwent 197 chemoembolization procedures (mean 3.6 ± 2.3 SD per patient). Thirty patients (30/55; 55%) had extrahepatic disease metastatic to the lungs, lymph nodes or peritoneum. Local tumor control was evaluated at 3, 6, 9 and 12 months. Median overall survival, survival rates at 1 and 2 year and adverse events were evaluated. Results: Local tumor control was achieved in 32/55 (58%), 12/55 (22%), 4/55 (7%) and 2/55 (4%) patients at 3, 6, 9 and 12 months, respectively. Median overall survival was 9.9 months (95% CI: 6.2–14.2 months) with 1- and 2-year survival rates of 45% and 15%, respectively. A total of 30 (15%) G1-G3 treatment-related adverse events occurred across all embolization procedures. No severe treatment-related adverse events occurred. Conclusion: Chemoembolization using irinotecan-loaded small-size beads is a safe and effective procedure as a salvage treatment in patients with colorectal liver metastases, showing good results in terms of liver-specific progression free survival and overall survival. [ABSTRACT FROM AUTHOR]