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Aim of our study was to assess the load of bone disease at starting and during Ra-223 treatment as an overall survival (OS) predictor in metastatic castration-resistant prostate cancer (mCRPC) patients. Bone scan index (BSI) is defined as the percentage of total amount of bone metastasis on whole-body scintigraphic images. We present a specific software (DASciS) developed by an engineering team of “Sapienza” University of Rome for BSI calculation.

Rosellina Margherita Mancina,1,* Flaminia Ferri,2,* Alessio Farcomeni,3 Antonio Molinaro,1 Angela Maffongelli,4 Monica Mischitelli,2 Edoardo Poli,2 Lucia Parlati,5 Maria Antonella Burza,6 Adriano De Santis,2 Fabio Attilia,2 Claudia Rotondo,2 Maria Margherita Rando,2 Maria Luisa Attilia,2 Mauro Ceccanti,2 Stefano Ginanni Corradini2 1Department of Molecular and Clinical Medicine, The Sahlgrenska Academy at the University of Gothenburg, Wallenberg Laboratory, Göteborg, Sweden; 2Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy; 3Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy; 4Department of General Surgery, Urgency and Organ Transplantation, University Hospital “Paolo Giaccone”, University of Palermo, Palermo, Italy; 5Hepatology Department, Université Paris Descartes, Cochin Hospital, APHP, Paris, France; 6Department of Medicine, Division of Gastroenterology and Hepatology, Sahlgrenska University Hospital, Gothenburg, Sweden *These authors contributed equally to this work Background: Alcoholic cirrhosis represents 1% of all cause-of-deaths worldwide. Its incidence is higher in males and results from the combination of environmental and genetic factors. Among all the genetic determinants of alcoholic cirrhosis, the patatin-like phospholipase domain protein 3 (PNPLA3) rs738409 represents the most widely validated determinant. Recent cross-sectional studies on alcohol abusers identified transmembrane-6 superfamily member 2 (TM6SF2) rs58542926, membrane bound O-acyltransferase domain containing 7 (MBOAT7) rs641738, and cluster of differentiation 14 (CD14) rs2569190 as new genetic risk factors for alcoholic cirrhosis. We aimed to develop a gene-based risk score to predict the incidence of alcoholic cirrhosis in males with at-risk alcohol consumption.Materials and methods: A total of 416 male at-risk alcohol drinkers were retrospectively examined. The association between alcoholic cirrhosis incidence and PNPLA3, CD14, TM6SF2, and MBOAT7 variants was tested. Age at onset of at-risk alcohol consumption, age, and body mass index (BMI) were included as covariates to determine the prediction score for alcoholic cirrhosis incidence by evaluating time-dependent receiver operating characteristic curves.Results: We found that PNPLA3, CD14, and TM6SF2 were associated with alcoholic cirrhosis prevalence. PNPLA3 and CD14 were also associated with its incidence. The best predictive score formula was (age at onset of at-risk alcohol consumption × 0.1) + (number of CD14 allele T) + (number of PNPLA3 allele M) + (BMI × 0.1). A threshold of 7.27 was identified as cutoff for the predictive risk of alcoholic cirrhosis development in 36 years from the onset of at-risk alcohol consumption with 70.1% sensitivity and 78.7% specificity.Conclusion: We developed the first score for alcoholic cirrhosis prediction that combines clinical and genetic factors. Keywords: alcoholic cirrhosis, PNPLA3, CD14, predictive score

Unsustainable exploitation of tropical forest resources is raising worldwide concern. In Papua New Guinea (PNG) timber harvesting has been identified as a major contributor to deforestation and forest degradation but its impact on biodiversity is still poorly understood. In this study we investigated the effect of selective logging on tree taxonomic composition, structure and diversity of PNG forests. We used data from 101 one-hectare permanent sample plots (PSPs) belonging to two vegetation types: low altitude forests on plains and fans (type P) and low altitude forests on uplands (type H). We used multivariate techniques to test for significant differences in species composition between plots of different vegetation types and disturbance regimes, identifying the tree taxa to which these differences could be ascribed. ANOVA was used to test for differences between logged-over and unlogged forest PSPs with respect to biodiversity (richness, Shannon’s diversity, Pielou’s evenness) and stand structure (stem density, basal area - BA). Temporal trends of forest features were analyzed using linear regression. Significant differences in taxonomic composition were found between logged-over and unlogged plots of the H type (p = 0.04). No differences were found in richness, diversity and evenness between logged-over and unlogged forest plots, while stem density was higher in the latter (421 ± 153 stems ha-1). Greater BA was found in unlogged forests (30.28 ± 4.45 m2 ha-1) of the H type when compared to the logged-over stands (15.52 ± 4.04 m2 ha-1). We detected positive trends in richness (0.55 ± 0.19 taxa ha-1 yr-1) and diversity after logging. Furthermore, H type forest exhibited positive trends in stem density (9 ± 1 stems ha-1 yr-1) and BA (0.42 ± 0.06 m2 ha-1 yr-1) with elapsed time since harvesting. Our analysis highlights some significant effects of logging activities on biodiversity and structure of PNG forests. Additionally, forests exhibited a significant recovery with respect to richness, diversity and stand structure. These preliminary results will be compared with data collected by the forthcoming National Forest Inventory in order to assess and monitor the effects of human activities and ecological factors on PNG forest biodiversity and develop appropriate conservation measures and sustainable management strategies.

Background: The bleeding risk of patients with atrial fibrillation (AF) changes over time. Most studies thus far evaluated only the baseline bleeding risk with discordant results. The impact of incident thrombocytopenia during direct oral anticoagulant (DOAC) therapy and its relation to bleeding has not been previously investigated. Objectives: To investigate the incidence rate of thrombocytopenia and major bleeding (MB) risk in AF patients on DOACs. Methods: Prospective ongoing ATHEROsclerosis in Atrial Fibrillation study including patients with nonvalvular AF on DOACs. Incident thrombocytopenia was defined as a platelet count

The influenza A(H1N1) pdm09 virus, which emerged in 2009, has been circulating seasonally since then. In this study, we conducted a comprehensive genome-based investigation to gain a detailed understanding of the genetic and evolutionary characteristics of the hemagglutinin (HA) and neuraminidase (NA) surface proteins of A/H1N1pdm09 strains circulating in Italy over a fourteen-year period from 2009 to 2023 in relation to global strains. Phylogenetic analysis revealed rapid transmission and diversification of viral variants during the early pandemic that clustered in clade 6B.1. In contrast, limited genetic diversity was observed during the 2023 season, probably due to the genetic drift, which provides the virus with a constant adaptability to the host; furthermore, all isolates were split into two main groups representing two clades, i.e., 6B.1A.5a.2a and its descendant 6B.1A.5a.2a.1. The HA gene showed a faster rate of evolution compared to the NA gene. Using FUBAR, we identified positively selected sites 41 and 177 for HA and 248, 286, and 455 for NA in 2009, as well as sites 22, 123, and 513 for HA and 339 for NA in 2023, all of which may be important sites related to the host immune response. Changes in glycosylation acquisition/loss at prominent sites, i.e., 177 in HA and 248 in NA, should be considered as a predictive tool for early warning signs of emerging pandemics, and for vaccine and drug development.

Background:. The fat-augmented latissimus dorsi (FALD) flap combines this pedicled flap with immediate intraoperative fat transfer. Very little is described concerning its inset at the mammary site. Our efforts have concentrated on seeking the best flap orientation and skin-adipose paddle shaping, to improve the aesthetic outcome and to obtain a complete breast reconstruction (BR) in one stage. Methods:. A prospective clinical study was performed in patients who underwent BR with FALD flaps, between December 2020 and March 2022. Patients were randomly enrolled into two groups: ergonomic inset of the FALD flap with vertical orientation of the skin-adipose paddle (group A) and FALD flap with traditional horizontal paddle orientation (group B). The study’s endpoints were the evaluation of the aesthetic outcomes (from patients’ and surgeon’s perspectives) and complications. Results:. Thirty-two FALD flaps (23 patients) were performed for group A, and 31 FALD flaps (25 patients) for group B. The two groups were homogeneous in terms of demographic and surgical data (P > 0.05). The overall complication rate was homogeneous among the groups, without statistically significant differences (P = 1.00). The surgeon’s assessments showed a statistically significant superior aesthetic outcome in group A regarding volume, symmetry, and shape (P < 0.05). Higher satisfaction was observed in group A patients, in terms of breast size (P < 0.00001), shape (P = 0.0049), and overall satisfaction (P = 0.00061). Conclusions:. The ergonomic vertical FALD flap technique enables surgeons to perform one-stage total BR, with excellent breast projection and upper pole fullness. These refinements in flap shaping and molding reduced the need for further autologous fat transfer, obtaining a brilliant totally autologous BR without the need for microsurgical experience.

The growing emergence of non-nucleoside reverse transcriptase inhibitor (NNRTI) HIV drug resistance in sub-Saharan Africa (SSA) led to the World Health Organization (WHO) recommending, in 2018, a transition to dolutegravir (DTG) as a first-line antiretroviral therapy (ART) in SSA. The broad HIV-1 genetic diversity in SSA could shape DTG effectiveness and the pattern of drug resistance mutations (DRMs) in this region. This study evaluated HIV-1 integrase (IN) DRMs and conserved regions among published groups M, N, O, and P HIV-1 sequences spanning forty years of the HIV epidemic during the transition of DTG-based ART. Overall, we found low levels of integrase strand transfer inhibitor (INSTI)-DRMs (

Background: Short-term forecasts of infectious disease burden can contribute to situational awareness and aid capacity planning. Based on best practice in other fields and recent insights in infectious disease epidemiology, one can maximise the predictive performance of such forecasts if multiple models are combined into an ensemble. Here, we report on the performance of ensembles in predicting COVID-19 cases and deaths across Europe between 08 March 2021 and 07 March 2022. Methods: We used open-source tools to develop a public European COVID-19 Forecast Hub. We invited groups globally to contribute weekly forecasts for COVID-19 cases and deaths reported by a standardised source for 32 countries over the next 1–4 weeks. Teams submitted forecasts from March 2021 using standardised quantiles of the predictive distribution. Each week we created an ensemble forecast, where each predictive quantile was calculated as the equally-weighted average (initially the mean and then from 26th July the median) of all individual models’ predictive quantiles. We measured the performance of each model using the relative Weighted Interval Score (WIS), comparing models’ forecast accuracy relative to all other models. We retrospectively explored alternative methods for ensemble forecasts, including weighted averages based on models’ past predictive performance. Results: Over 52 weeks, we collected forecasts from 48 unique models. We evaluated 29 models’ forecast scores in comparison to the ensemble model. We found a weekly ensemble had a consistently strong performance across countries over time. Across all horizons and locations, the ensemble performed better on relative WIS than 83% of participating models’ forecasts of incident cases (with a total N=886 predictions from 23 unique models), and 91% of participating models’ forecasts of deaths (N=763 predictions from 20 models). Across a 1–4 week time horizon, ensemble performance declined with longer forecast periods when forecasting cases, but remained stable over 4 weeks for incident death forecasts. In every forecast across 32 countries, the ensemble outperformed most contributing models when forecasting either cases or deaths, frequently outperforming all of its individual component models. Among several choices of ensemble methods we found that the most influential and best choice was to use a median average of models instead of using the mean, regardless of methods of weighting component forecast models. Conclusions: Our results support the use of combining forecasts from individual models into an ensemble in order to improve predictive performance across epidemiological targets and populations during infectious disease epidemics. Our findings further suggest that median ensemble methods yield better predictive performance more than ones based on means. Our findings also highlight that forecast consumers should place more weight on incident death forecasts than incident case forecasts at forecast horizons greater than 2 weeks. Funding: AA, BH, BL, LWa, MMa, PP, SV funded by National Institutes of Health (NIH) Grant 1R01GM109718, NSF BIG DATA Grant IIS-1633028, NSF Grant No.: OAC-1916805, NSF Expeditions in Computing Grant CCF-1918656, CCF-1917819, NSF RAPID CNS-2028004, NSF RAPID OAC-2027541, US Centers for Disease Control and Prevention 75D30119C05935, a grant from Google, University of Virginia Strategic Investment Fund award number SIF160, Defense Threat Reduction Agency (DTRA) under Contract No. HDTRA1-19-D-0007, and respectively Virginia Dept of Health Grant VDH-21-501-0141, VDH-21-501-0143, VDH-21-501-0147, VDH-21-501-0145, VDH-21-501-0146, VDH-21-501-0142, VDH-21-501-0148. AF, AMa, GL funded by SMIGE - Modelli statistici inferenziali per governare l'epidemia, FISR 2020-Covid-19 I Fase, FISR2020IP-00156, Codice Progetto: PRJ-0695. AM, BK, FD, FR, JK, JN, JZ, KN, MG, MR, MS, RB funded by Ministry of Science and Higher Education of Poland with grant 28/WFSN/2021 to the University of Warsaw. BRe, CPe, JLAz funded by Ministerio de Sanidad/ISCIII. BT, PG funded by PERISCOPE European H2020 project, contract number 101016233. CP, DL, EA, MC, SA funded by European Commission - Directorate-General for Communications Networks, Content and Technology through the contract LC-01485746, and Ministerio de Ciencia, Innovacion y Universidades and FEDER, with the project PGC2018-095456-B-I00. DE., MGu funded by Spanish Ministry of Health / REACT-UE (FEDER). DO, GF, IMi, LC funded by Laboratory Directed Research and Development program of Los Alamos National Laboratory (LANL) under project number 20200700ER. DS, ELR, GG, NGR, NW, YW funded by National Institutes of General Medical Sciences (R35GM119582; the content is solely the responsibility of the authors and does not necessarily represent the official views of NIGMS or the National Institutes of Health). FB, FP funded by InPresa, Lombardy Region, Italy. HG, KS funded by European Centre for Disease Prevention and Control. IV funded by Agencia de Qualitat i Avaluacio Sanitaries de Catalunya (AQuAS) through contract 2021-021OE. JDe, SMo, VP funded by Netzwerk Universitatsmedizin (NUM) project egePan (01KX2021). JPB, SH, TH funded by Federal Ministry of Education and Research (BMBF; grant 05M18SIA). KH, MSc, YKh funded by Project SaxoCOV, funded by the German Free State of Saxony. Presentation of data, model results and simulations also funded by the NFDI4Health Task Force COVID-19 (https://www.nfdi4health.de/task-force-covid-19-2) within the framework of a DFG-project (LO-342/17-1). LP, VE funded by Mathematical and Statistical modelling project (MUNI/A/1615/2020), Online platform for real-time monitoring, analysis and management of epidemic situations (MUNI/11/02202001/2020); VE also supported by RECETOX research infrastructure (Ministry of Education, Youth and Sports of the Czech Republic: LM2018121), the CETOCOEN EXCELLENCE (CZ.02.1.01/0.0/0.0/17-043/0009632), RECETOX RI project (CZ.02.1.01/0.0/0.0/16-013/0001761). NIB funded by Health Protection Research Unit (grant code NIHR200908). SAb, SF funded by Wellcome Trust (210758/Z/18/Z).

Background: The incidence of new‐onset atrial fibrillation (NOAF) is increasing in the last decades. NOAF is associated with worse long‐term prognosis. The C2HEST score has been recently proposed to stratify the risk of NOAF. Pooled data on the performance of the C2HEST score are lacking. Methods: Systematic review and meta‐analysis of observational studies reporting data on NOAF according to the C2HEST score. We searched PubMed, Web of Science and Google scholar databases without time restrictions until June 2023 according to PRISMA guidelines. Meta‐analysis of the area under the curve (AUC) with 95% confidence interval (95% CI) and a sensitivity analysis according to setting of care and countries were performed. Results: Of 360 studies, 17 were included in the analysis accounting for 11,067,496 subjects/patients with 307,869 NOAF cases. Mean age ranged from 41.3 to 71.2 years. The prevalence of women ranged from 10.6 to 54.75%. The pooled analysis gave an AUC of.70 (95% CI.66–.74). A subgroup analysis on studies from general population/primary care yielded an AUC of 0.69 (95% CI 0.64–0.75). In the subgroup of patients with cardiovascular disease, the AUC was.71 (.69–.79). The C2HEST score performed similarly in Asian (AUC.72, 95% CI.68–.77), and in Western patients (AUC.68, 95% CI.62–.75). The best performance was observed in studies with a mean age <50 years (n = 3,144,704 with 25,538 NOAF, AUC.78, 95% CI.76–.79). Conclusion: The C2HEST score may be used to predict NOAF in primary and secondary prevention patients, and in patients across different countries. Early detection of NOAF may aid prompt initiation of management and follow‐up, potentially leading to a reduction of AF‐related complications. [ABSTRACT FROM AUTHOR]

AbstractWe present parametric and semiparametric latent Markov time-interaction processes, that are point processes where the occurrence of an event can increase or reduce the probability of future events. We first present time-interaction processes with parametric and nonparametric baselines, then we let model parameters be modulated by a discrete state continuous time latent Markov process. Posterior inference is based on a novel and efficient data augmentation approach in the Markov Chain Monte Carlo framework. We illustrate with a simulation study; and an original application to terrorist attacks in Europe in the period 2001-2017, where we find two distinct latent clusters for the hazard of occurrence of terrorist events, negative association with GDP growth, and self-exciting phenomena. [ABSTRACT FROM AUTHOR]

Background: Parkinson’s disease is a progressive neurodegenerative disorder, with incidence and prevalence rates of 8–18 per 100,000 people per year and 0.3–1%, respectively. As parkinsonian symptoms do not appear until approximately 50–60% of the nigral DA-releasing neurons have been lost, the impact of routine structural imaging findings is minimal at early stages, making Parkinson’s disease an ideal condition for the application of functional imaging techniques. The aim of this multicenter study is to assess whether 123I-FP-CIT (DAT-SPECT), 123I-MIBG (mIBG-scintigraphy) or an association of both exams presents the highest diagnostic accuracy in de novo PD patients. Methods: 288 consecutive patients with suspected diagnoses of Parkinson’s disease or non- Parkinson’s disease syndromes were analyzed in the present Italian multicenter retrospective study. All subjects were de novo, drug-naive patients and met the inclusion criteria of having undergone both DAT-SPECT and mIBG-scintigraphy within one month of each other. Results: The univariate analysis including age and both mIBG-SPECT and DAT-SPECT parameters showed that the only significant values for predicting Parkinson’s disease in our population were eH/M, lH/M, ESS and LSS obtained from mIBG-scintigraphy (p < 0.001). Conclusions: mIBG-scintigraphy shows higher diagnostic accuracy in de novo Parkinson’s disease patients than DAT-SPECT, so given the superiority of the MIBG study, the combined use of both exams does not appear to be mandatory in the early phase of Parkinson’s disease.

Background/Aim: Radium-223 dichloride (223RaCl2) represents a therapeutic option for metastatic castration-resistant prostate cancer (mCRPC) patients dealing with symptomatic bone metastases. The identification of baseline variables potentially affecting the life-prolonging role of 223RaCl2 is still ongoing. Bone scan index (BSI) defines the total load of bone metastatic disease detected on a bone scan (BS) and is expressed as a percentage value of the whole bone mass. The aim of this multicenter study was to assess the impact of baseline BSI on overall survival (OS) in mCRPC patients treated with 223RaCl2. For this purpose, the DASciS software developed by the Sapienza University of Rome for BSI calculation was shared between six Italian Nuclear Medicine Units. Methods: 370 pre-treatment BS were analyzed through the DASciS software. Other clinical variables relevant to OS analysis were taken into account for the statistical analysis. Results: Of a total of 370 patients, 326 subjects had died at the time of our retrospective analysis. The median OS time from the first cycle of 223RaCl2 to the date of death from any cause or last contact was 13 months (95%CI 12–14 months). The mean BSI value resulted in 2.98% ± 2.42. The center-adjusted univariate analysis showed that baseline BSI was significantly associated with OS as an independent risk factor (HR 1.137, 95%CI: 1.052–1.230, p = 0.001), meaning that patients with higher BSI values had worse OS. When adjusting for other measures on multivariate analysis, in addition to Gleason score and baseline values of Hb, tALP, and PSA, baseline BSI was confirmed to be a statistically significant parameter (HR 1.054, 95%CI: 1.040–1.068, p < 0.001). Conclusions: Baseline BSI significantly predicts OS in mCRPC treated with 223RaCl2. The DASciS software was revealed to be a valuable tool for BSI calculation, showing rapid processing time and requiring no more than a single demonstrative training for each participating center.

Latissimus Dorsi (LD) flap is at present among the best techniques for autologous breast reconstruction. A reliable pre-operatory estimation of flap volume would enhance surgical planning, thus improving the aesthetic outcomes of the reconstruction and reducing the need of secondary revision procedures. The study was aimed at providing a simple and reproducible formula to predict LD flap volume pre-operatively. 61 patients (66 flaps) who underwent breast reconstruction with LD flap at Policlinico Tor Vergata were prospectively enroled in the study. Anthropometric data and flap measurements were collected pre-operatively. LD flap volume was determined intraoperatively utilising a water displacement technique. A multivariate regression analysis was performed to analyse the collected data and to obtain the mathematical model that most accurately predicts flap volume. The mean actual LD flap volume calculated through water displacement was 213.14 cc (SD 64.56). Performing a multivariate regression analysis BMI and skin paddle width emerged as the most accurate predictors of Latissimus Dorsi flap volume. The mean predicted LD flap volume (LD-V) using the LD-V formula was 213.19 cc (SD 54.59), with a strong Pearson correlation (r = 0.845; R2 =0.715) with the volume calculated through the water displacement technique. The LD-V formula is an easy and reliable tool for LD flap volume assessment, available as 3.0 WebApp at www.braflap.com , that can be used as a valuable adjunct to surgeon's subjective evaluation to optimise breast reconstruction with the LD flap. II [ABSTRACT FROM AUTHOR]

We propose novel quantile regression methods when the response is discrete and the data come from a longitudinal design. The approach is based on conditional mid-quantiles, which have good theoretical properties even in the presence of ties. Optimization of a ridge-type penalized objective function accommodates for the data dependence. We investigate the performance and pertinence of our methods in a simulation study and an original application to macroprudential policies use in more than one hundred countries over a period of seventeen years. [ABSTRACT FROM AUTHOR]

We derive a multivariate latent Markov model with number of latent states that can possibly change at each time point. We model both the manifest and latent distributions conditionally on explanatory variables. Bayesian inference is based on a transdimensional Markov Chain Monte Carlo approach, where Reversible Jump is separately performed for each time occasion. In a simulation study, we show how our approach can recover the true underlying sequence of latent states with high probability, and that it has lower bias than competitors. We conclude with an analysis of the well-being of 100 nations, as expressed by the dimensions of the Human Development Index, for six-time points spanning a period of 22 years. R code with an implementation is available as supplementary material, together with files for reproducing the data analysis. [ABSTRACT FROM AUTHOR]

The epigenetic background of pluripotent stem cells can influence transcriptional and functional behavior. Most of these data have been obtained in standard monolayer cell culture systems. In this study, we used exome sequencing, array comparative genomic hybridization (CGH), miRNA array, DNA methylation array, three-dimensional (3D) tissue engineering, and immunostaining to conduct a comparative analysis of two induced pluripotent stem cell (iPSC) lines used in engineering of 3D human epidermal equivalent (HEE), which more closely approximates epidermis. Exome sequencing and array CGH suggested that their genome was stable following 3 months of feeder-free culture. While the miRNAome was also not affected, ≈7% of CpG sites were differently methylated between the two lines. Analysis of the epidermal differentiation complex, a region on chromosome 1 that contains multiple genes involved in skin barrier maturation (including trichohyalin, TCHH), found that in one of the iPSC clones (iKCL004), TCHH retained a DNA methylation signature characteristic of the original somatic cells, whereas in other iPSC line (iKCL011), the TCHH methylation signature matched that of the human embryonic stem cell line KCL034. The difference between the two iPSC clones in TCHH methylation did not have an obvious effect on its expression in 3D HEE, suggesting that differentiation and tissue formation may mitigate variations in the iPSC methylome.