Search

Although shown to be effective in improving survival and quality of life in patients with cancer, some treatments are well-known causes of cardiotoxicity, such as anthracyclines, monoclonal antibodies against human epidermal growth factor receptor 2 (HER2) and radiotherapy. To prevent cardiovascular disease (CVD) in patients living with cancer, cardiologists and oncologists promoted the development of cardio-oncology, an interdisciplinary field which aims to further improving life expectancy in these patients. Cardio-oncology rehabilitation (CORE), through correction of risk factors, prescription of drug therapies and structured exercise programs, tries to improve symptoms, quality of life, cardiorespiratory fitness (CRF) and survival in patients with cancer. Different imaging modalities can be used to evaluate the real effectiveness of exercise training on cardiac function. Among these, the global longitudinal strain (GLS) has recently aroused interest, thanks to its high sensitivity and specificity for cardiac dysfunction detection due to advanced ultrasound programs. This review summarizes the evidence on the usefulness of GLS in patients with cancer undergoing cardiac rehabilitation programs.

BACKGROUND: Enrichment strategies from clinical trials for progressive systemic sclerosis-associated interstitial lung disease (SSc-ILD) have not been tested in a real-life cohort.RESEARCH QUESTION: Do enrichment strategies for progressive ILD impact efficacy, repre-sentativeness, and feasibility in patients with SSc-ILD from the European Scleroderma Trials and Research (EUSTAR) database?STUDY DESIGN AND METHODS: We applied the inclusion criteria of major recent SSc-ILD trials (Study of the Efficacy and Safety of Tocilizumab in Participants With Systemic Sclerosis [focuSSced], Scleroderma Lung Study II [SLS II], and Safety and Efficacy of Nintedanib in Systemic Sclerosis [SENSCIS]) and assessed progressive ILD, which was defined as absolute change in FVC and as significant progression (FVC decline $10%). Data were compared with all patients and with patients who did not fulfill any inclusion criteria. RESULTS: In total, 2,258 patients with SSc-ILD were included: 31.2% of the patients met SENSCIS criteria; 5.8% of the patients met SLS II criteria; 1.6% of the patients met focuSSced criteria, and 67.7% (1,529) of the patients did not meet any criteria. In the first 12 + 3 months, the absolute FVC decline in all patients and in patients who fulfilled criteria from SENSCIS was -0.1%, in patients who fulfilled criteria from focuSSced was -3.7%, and in patients who fulfilled criteria from SLS II was 2.3%, with accompanying more progressors in focuSSced. The patient populations that fulfilled the different study inclusion criteria significantly differed in various clinical parameters. In the second 12-month period, SENSCIS-enriched patients had a further absolute FVC% decline as described for the total cohort. In contrast, patients who fulfilled the focuSSced and SLS II criteria showed numeric improvement of lung function. There were no significant associations of enrichment criteria and ILD progression.INTERPRETATION: The application of enrichment criteria from previous clinical trials showed enrichment for progression with variable success, which led to selected patient populations reducing feasibility of recruitment. These findings are important for future clinical trial design and interpretation of the results of published trials.CHEST 2023; 163(3):586-598

Renal Cell Carcinoma (RCC) is generally characterized by low-FDG avidity, and [18F]FDG-PET/CT is not recommended to stage the primary tumor. However, its role to assess metastases is still unclear. The aim of this study was to evaluate the diagnostic accuracy of [18F]FDG-PET/CT in correctly identifying RCC lung metastases using histology as the standard of truth. The records of 350 patients affected by RCC were retrospectively analyzed. The inclusion criteria were: (a) biopsy- or histologically proven RCC; (b) Computed Tomography (CT) evidence of at least one lung nodule; (c) [18F]FDG-PET/CT performed prior to lung surgery; (d) lung surgery with histological analysis of surgical specimens; (e) complete follow-up available. A per-lesion analysis was performed, and diagnostic accuracy was reported as sensitivity and specificity, using histology as the standard of truth. [18F]FDG-PET/CT semiquantitative parameters (Standardized Uptake Value [SUVmax], Metabolic Tumor Volume [MTV] and Total Lesion Glycolysis [TLG]) were collected for each lesion. Sixty-seven patients with a total of 107 lesions were included: lung metastases from RCC were detected in 57 cases (53.3%), while 50 lesions (46.7%) were related to other lung malignancies. Applying a cut-off of SUVmax ≥ 2, the sensitivity and the specificity of [18F]FDG-PET/CT in detecting RCC lung metastases were 33.3% (95% CI: 21.4–47.1%) and 26% (95%CI: 14.6–40.3%), respectively. Although the analysis demonstrated a suboptimal diagnostic accuracy of [18F]FDG-PET/CT in discriminating between lung metastases from RCC and other malignancies, a semiquantitative analysis that also includes volumetric parameters (MTV and TLG) could support the correct interpretation of [18F]FDG-PET/CT images.

Nowadays, time series are a widely-exploited methodology to describe phenomena belonging to different fields. In fact, electrical consumption can be explained, from a data analysis perspective, with a time series, as for healthcare, financial index, air pollution or parking occupancy rate. Applying time series to different areas of interest has contributed to the exponential rise in interest by both practitioners and academics. On the other side, especially regarding static data, a new trend is acquiring even more relevance in the data analysis community, namely neural network generative approaches. Generative approaches aim to generate new, fake samples given a dataset of real data by implicitly learning the probability distribution underlining data. In this way, several tasks can be addressed, such as data augmentation, class imbalance, anomaly detection or privacy. However, even if this topic is relatively well-established in the literature related to static data regarding time series, the debate is still open. This paper contributes to this debate by comparing four neural network-based generative approaches for time series belonging to the state-of-the-art methodologies in literature. The comparison has been carried out on five public and private datasets and on different time granularities, with a total number of 13 experimental scenario. Our work aims to provide a wide overview of the performances of the compared methodologies when working in different conditions like seasonality, strong autoregressive components and long or short sequences.

Abstract domains of knowledge may have social origins. However, whether abstract concepts (ACs) may also differentially affect communicative interaction and conversation has not been explored. Here, we studied ACs’ communicative functions by collecting in an Italian and an English sample, ratings for concrete concept (CC) and ACs related to three main dimensions: communicative/pragmatic [i.e., Openness to Negotiation (ON), Easiness to Start a Conversation (ESC)], semantic/metacognitive [i.e., Social Metacognition (SM) – perceived need of others, Word Confidence (WC), Contextual Availability (CA)], and emotional–experiential (i.e., Pleasantness, Valence, Familiarity). Overall, Italian participants judged it was easier to start a conversation, the more pleasant, familiar, and positively valenced were rated the concepts. Crucially, at lower values of the emotional–experiential component (i.e., Familiarity in the Italian sample, also Pleasantness and Valence in an English sample), there was an advantage of ACs over CCs in the ESC. Moreover, in the Italian sample, participants rated ACs higher on SM, ON, and lower on WC and CA. Notably, in both the Italian and English sample, ACs with higher ratings on the ESC dimension belonged to the Self-Sociality subcluster. The results offer new insights into the pragmatic aspects linked to ACs’ use.

We investigate the link between the bar rotation rate and dark matter content in barred galaxies by concentrating on the cases of the lenticular galaxies NGC4264 and NGC4277. These two gas-poor galaxies have similar morphologies, sizes, and luminosities. But, NGC4264 hosts a fast bar, which extends to nearly the corotation, while the bar embedded in NGC4277 is slow and falls short of corotation. We derive the fraction of dark matter $f_{\rm DM, bar}$ within the bar region from Jeans axisymmetric dynamical models by matching the stellar kinematics obtained with the MUSE integral-field spectrograph and using SDSS images to recover the stellar mass distribution. We build mass-follows-light models as well as mass models with a spherical halo of dark matter, which is not tied to the stars. We find that the inner regions of NGC4277 host a larger fraction of dark matter ($f_{\rm DM, bar} = 0.53 \pm 0.02$) with respect to NGC4264 ($f_{\rm DM, bar} = 0.33 \pm 0.04$) in agreement with the predictions of theoretical works and the findings of numerical simulations, which have found that fast bars live in baryon-dominated discs, whereas slow bars experienced a strong drag from the dynamical friction due to a dense DM halo. This is the first time that the bar rotation rate is coupled to $f_{\rm DM, bar}$ derived from dynamical modelling., Accepted for publication on MNRAS, 12 pages

Funder: Kennedy Trust Rheumatology Research Prize Studentship, Funder: DFG Cluster of Excellence ���Precision Medicine in Chronic In-flammation��� (PMI; ID: EXC2167), Funder: EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: ���Ideas��� Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013)); doi: https://doi.org/10.13039/100011199; Grant(s): 715772, Funder: NWO-VIDI grant 016.178.056, the Netherlands Heart Foundation CVON grant 2018-27, and NWO Gravitation grant ExposomeNL, Funder: Li Ka Shing Foundation (Li Ka Shing Foundation Limited); doi: https://doi.org/10.13039/100007421, Irritable bowel syndrome (IBS) results from disordered brain���gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiological mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS with independent cohorts. We conducted a genome-wide association study with 53,400 cases and 433,201 controls and replicated significant associations in a 23andMe panel (205,252 cases and 1,384,055 controls). Our study identified and confirmed six genetic susceptibility loci for IBS. Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6. The first four are associated with mood and anxiety disorders, expressed in the nervous system, or both. Mirroring this, we also found strong genome-wide correlation between the risk of IBS and anxiety, neuroticism and depression (rg > 0.5). Additional analyses suggested this arises due to shared pathogenic pathways rather than, for example, anxiety causing abdominal symptoms. Implicated mechanisms require further exploration to help understand the altered brain���gut interactions underlying IBS.

Objective To develop and validate the prognostic prediction model DU-VASC to assist the clinicians in decision-making regarding the use of platelet inhibitors (PIs) for the management of digital ulcers in patients with systemic sclerosis. Secondly, to assess the incremental value of PIs as predictor. Methods We analysed patient data from the European Scleroderma Trials and Research group registry (one time point assessed). Three sets of derivation/validation cohorts were obtained from the original cohort. Using logistic regression, we developed a model for prediction of digital ulcers (DUs). C-Statistics and calibration plots were calculated to evaluate the prediction performance. Variable importance plots and the decrease in C-statistics were used to address the importance of the predictors. Results Of 3710 patients in the original cohort, 487 had DUs and 90 were exposed to PIs. For the DU-VASC model, which includes 27 predictors, we observed good calibration and discrimination in all cohorts (C-statistic = 81.1% [95% CI: 78.9%, 83.4%] for the derivation and 82.3% [95% CI: 779.3%, 85.3%] for the independent temporal validation cohort). Exposure to PIs was associated with absence of DUs and was the most important therapeutic predictor. Further important factors associated with absence of DUs were lower modified Rodnan skin score, anti-Scl-70 negativity and normal CRP. Conversely, the exposure to phosphodiesterase-5 inhibitor, prostacyclin analogues or endothelin receptor antagonists seemed to be associated with the occurrence of DUs. Nonetheless, previous DUs remains the most impactful predictor of DUs. Conclusion The DU-VASC model, with good calibration and discrimination ability, revealed that PI treatment was the most important therapy-related predictor associated with reduced DU occurrence.

Objectives It has recently become possible to assess lung vascular and parenchymal changes quantitatively in thoracic CT images using automated software tools. We investigated the vessel parameters of patients with SSc, quantified by CT imaging, and correlated them with interstitial lung disease (ILD) features. Methods SSc patients undergoing standard of care pulmonary function testing and CT evaluation were retrospectively evaluated. CT images were analysed for ILD patterns and total pulmonary vascular volume (PVV) extents with Imbio lung texture analysis. Vascular analysis (volumes, numbers and densities of vessels, separating arteries and veins) was performed with an in-house developed software. A threshold of 5% ILD extent was chosen to define the presence of ILD, and commonly used cut-offs of lung function were adopted. Results A total of 79 patients [52 women, 40 ILD, mean age 56.2 (s.d. 14.2) years, total ILD extent 9.5 (10.7)%, PVV/lung volume % 2.8%] were enrolled. Vascular parameters for total and separated PVV significantly correlated with functional parameters and ILD pattern extents. SSc-associated ILD (SSc-ILD) patients presented with an increased number and volume of arterial vessels, in particular those between 2 and 4 mm of diameter, and with a higher density of arteries and veins of Conclusion In SSc patients CT vessel parameters increase in parallel with ILD extent and functional impairment, and may represent a biomarker of SSc-ILD severity.

LoRaWAN (Long Range WAN) is one of the well-known emerging technologies for the Internet of Things (IoT). Many IoT applications involve simple devices that transmit their data toward network gateways or access points that, in their turn, redirect data to application servers. While several security issues have been addressed in the LoRaWAN specification v1.1, there are still some aspects that may undermine privacy and security of the interconnected IoT devices. In this paper, we tackle a privacy aspect related to LoRaWAN device identity. The proposed approach, by monitoring the network traffic in LoRaWAN, is able to derive, in a probabilistic way, the unique identifier of the IoT device from the temporal address assigned by the network. In other words, the method identifies the relationship between the LoRaWAN DevAddress and the device manufacturer DevEUI. The proposed approach, named DEVIL (DEVice Identification and privacy Leakage), is based on temporal patterns arising in the packets transmissions. The paper presents also a detailed study of two real datasets: i) one derived by IoT devices interconnected to a prominent network operator in Italy; ii) one taken from the literature (the LoED dataset in Bhatia et al. (2020)). DEVIL is evaluated on the first dataset while the second is analyzed to support the hypothesis under the DEVIL operation. The results of our analysis, compared with other literature approaches, show how device identification through DEVIL can expose IoT devices to privacy leakage. Finally, the paper also provides some guidelines to mitigate the user re-identification threats.

Background/Aim: Telemedicine, the remote delivery of healthcare services, represents a great opportunity for cancer pain management. A care model of telemedicine that combines remote visits and hospital access could be an effective and safe strategy for pain management of cancer patients. Patients and Methods: A retrospective study was conducted using the dataset of the telemedicine program at the Istituto Nazionale Tumori of Naples, Italy for assessing the efficacy of a telehealth-based model of care. Demographic, clinical, and process variables were investigated. Results: A total of 226 cases and 489 visits were included in the analysis. The mean age of patients was 63.4 years (SD=12.4 years), and no sex differences were observed. Approximately 55% of patients were ECOG-PS ≤2 and 87% suffered from metastatic disease. More than half of the patients were treated with high doses of opioids. Each patient had a mean of 2 remote visits and half of the patients had more than 1 telehealth consultation. The dropout ratio was 5.3%. Most visits (n=472) were conducted on patients in the Campania Region, Italy. The maximum covered distance from the Cancer Center and the patients’ location was 555.22 Km. A significant difference in the overall number of visits (p=0.006) and the number of pro-capita remote visits (p=0.010) was found, in favor of the group of patients treated before the end of the Covid-19 emergency in Italy, compared to those treated after the pandemic. Conclusion: Despite various positive outcomes, the analysis highlights several weaknesses, such as the need to assist patients with advanced and non-advanced disease located outside the regional territory. Overall, the telehealth processes should be adapted to post-pandemic scenarios towards their implementation in routine clinical practice.

Traditionally-cationic poly(β-amino ester)s with two anionic sulfonate groups per tertiary amine display non-monotonic solution behavior as a function of pH.

This article publishes an annotated edition of a previously unknown account of the myth of Procne and Philomela. It is about a relatively long scholion on Soph. El. 147–149 preserved in the Moschopulean manuscript of Vienna, Österreichische Nationalbibliothek (ÖNB), Phil. gr. 161 (Diktyon 71275) (= Xr), copied by Konstantinos ὁ Κετζᾶς (ho Ketzas) in 1412. The scholion will be examined in the context of the Moschopulean manuscripts of Sophocles. The narrative will be compared with other Greek and Latin accounts of the myth of Procne and Philomela, emphasizing the characteristics of the scholion. While direct parallels to other sources cannot be spotted and its origin remains unknown, Xr’s scholion displays similarities to the Trikilinian scholia on Aristophanes’ Aves 212e, α and β (HOLWERDA 1991), Tzetzes’ scholion on Hesiod’s Opera et Dies 568 Πανδιονίς (Pandionis; 566ter GAISFORD 1823), and with Eustathios’ Commentarii ad Homeri Odysseam (II 215,13 STALLBAUM 1826)

5G and beyond mobile networks will support heterogeneous use cases at an unprecedented scale, thus demanding automated control and optimization of network functionalities customized to the needs of individual users. Such fine-grained control of the Radio Access Network (RAN) is not possible with the current cellular architecture. To fill this gap, the Open RAN paradigm and its specification introduce an open architecture with abstractions that enable closed-loop control and provide data-driven, and intelligent optimization of the RAN at the user level. This is obtained through custom RAN control applications (i.e., xApps) deployed on near-real-time RAN Intelligent Controller (near-RT RIC) at the edge of the network. Despite these premises, as of today the research community lacks a sandbox to build data-driven xApps, and create large-scale datasets for effective AI training. In this paper, we address this by introducing ns-O-RAN, a software framework that integrates a real-world, production-grade near-RT RIC with a 3GPP-based simulated environment on ns-3, enabling the development of xApps and automated large-scale data collection and testing of Deep Reinforcement Learning-driven control policies for the optimization at the user-level. In addition, we propose the first user-specific O-RAN Traffic Steering (TS) intelligent handover framework. It uses Random Ensemble Mixture, combined with a state-of-the-art Convolutional Neural Network architecture, to optimally assign a serving base station to each user in the network. Our TS xApp, trained with more than 40 million data points collected by ns-O-RAN, runs on the near-RT RIC and controls its base stations. We evaluate the performance on a large-scale deployment, showing that the xApp-based handover improves throughput and spectral efficiency by an average of 50% over traditional handover heuristics, with less mobility overhead., 15 pages, 2 algorithms, 1 table, 11 figures, 42 references

To assay the presence of the SARS-CoV-2 genome in vaginal, rectal, and placental swabs among pregnant women and in newborn nasopharyngeal swabs and to investigate the immunological response and maternal antibody transfer through the umbilical cord blood and milk of unvaccinated mothers.Vaginal, rectal, and placental specimens, maternal and neonatal serum, and milk were collected from a wide cohort of pregnant Italian women with confirmed SARS-CoV-2 infection admitted to the hospital between February 25, 2020 and June 30, 2021. Samples were tested in selected reference laboratories according to a shared interlaboratory protocol.Among 1086 enrolled women, the SARS-CoV-2 positive rate detected in all specimens ranged from 0.7% to 8.4%. Respectively, 45.2% of maternal sera collected during pregnancy and 39.7% of those collected at birth tested positive for immunoglobulin G, whereas 50.5% tested positive among neonates. Nasopharyngeal swabs were positive in 0.8% of the newborns, and immunoglobulin G was detected in 3.0% of the milk samples. The highest immunological response was recorded within 30 days during pregnancy and within 60 days of birth and in the neonatal population.Vertical transmission should be considered a rare event; although, a good maternal immunological response and antibodies transfer throughout the umbilical cord blood was detected.

Background Fluid overload is a serious complication in the treatment of infants with extracorporeal membrane oxygenation (ECMO). Volume overload leads to prolonged ECMO therapy if left untreated. The renal replacement therapy of choice in pediatric patients is peritoneal dialysis or conventional dialysis using a “large” hemofiltration machine via a Shaldon catheter or directly connected to the ECMO system. This study describes the implementation of a novel minimized hemodiafiltration (HDF) system in pediatric patients on ECMO. Methods This retrospective analysis included 13 infants up to 5 kg who underwent 15 veno-arterial (V-A) ECMO runs with HDF. A minimized HDF system is integrated into an existing ECMO system (18 mL priming volume), connected post-oxygenation to the venous line, before the ECMO pump. Two infusion pumps are attached to the inlet and outlet of the hemofilter to control the HDF system.In addition to retention values (creatine and urea) at six defined time points, flow rates, dialysis parameters, and volume withdrawal were examined, as well as the number of HDF system changes. Results With a mean ECMO runtime of 156 hours, the HDF system was utilized for 131 hours. The mean blood flow through the hemofilter was 192 mL/min. The mean dialysate flow was 170 mL/h, with a mean volume deprivation of 39 mL/h. The HDF system was changed once in seven cases and twice in three cases. Conclusion There were no complications with the minimized HDF system in all 15 applications. It allows safe patient volume management when treating infants with ECMO, with effective elimination of urinary substances.

Background: The scientific literature on Artificial Intelligence (AI) in anesthesia is rapidly growing. Considering that applications of AI strategies can offer paramount support in clinical decision processes, it is crucial to delineate the research features. Bibliometric analyses can provide an overview of research tendencies useful for supplementary investigations in a research field. Methods: The comprehensive literature about AI in anesthesia was checked in the Web of Science (WOS) core collection. Year of publication, journal metrics including impact factor and quartile, title, document type, topic, and article metric (citations) were extracted. The software tool VOSviewer (version 1.6.17) was implemented for the co-occurrence of keywords and the co-citation analyses, and for evaluating research networks (countries and institutions). Results: Altogether, 288 documents were retrieved from the WOS and 154 articles were included in the analysis. The number of articles increased from 4 articles in 2017 to 37 in 2021. Only 34 were observational investigations and 7 RCTs. The most relevant topic is “anesthesia management”. The research network for countries and institutions shows severe gaps. Conclusion: Research on AI in anesthesia is rapidly developing. Further clinical studies are needed. Although different topics are addressed, scientific collaborations must be implemented.

Corruption is a complex system. Corruptors operate on the material and cognitive levels to insert corruption into the shared ethos.The aim is to reflect on corruption in Western democracy, through an ethical, philosophical-political and anthropological understanding, with regard to subjectification, linked to identity and belonging that psychoanalysis and political symbolism investigate.The methodology will be multidisciplinary.The fertile ground for corruption is the lack of development of “thoughtfulness”, an interior and relational space in which, starting from the caregiver’s relationship with the infant, the conscious and responsible subject is built. For Mary Douglas it is necessary to study identity and belonging of a family or individualistic type.

Queensborough Community College is one of six community colleges of the City University of New York. Located in Bayside, Queens, the college serves more than 15,000 degree students. Queens County in New York City is the most diverse county in the United States. The College reflects this diversity. Its White, Black, Hispanic, and Asian students or their families come from 143 countries including Paraguay, Venezuela, Korea, China, India, Guyana, Pakistan, Haiti and many more. Among the numerous languages they speak are Spanish, French, Urdu, Hindi, Punjabi, Chinese, Pushto, and Farsi. Almost half of them speak a language other than English at home. This diversity generates both challenges and opportunities in a college community. Historically, non-ESL students have scored 20 percent higher in pass rates for reading and 10 percent for writing. Queensborough Community College is an Hispanic Serving Institution with a 26% Hispanic population.

Adhesion formation following gynecological surgery remains a challenge. The adoption of minimally invasive surgical approaches, such as conventional or robotic-assisted laparoscopy combined with meticulous microsurgical principles and the application of adhesion–reducing substances, is able to reduce the risk of de novo adhesion formation but do not eliminate it entirely. Myomectomy is the most adhesiogenic surgical procedure and postoperative adhesions can have a significant impact on the ability to conceive. Therefore, when surgery is performed as infertility treatment, attention should be paid to whether the benefits outweigh the risks. Among several factors, the size and the location of fibroids are the most accountable factors in terms of adhesion development and post surgical infertility; therefore, the search for effective strategies against adhesion formation in this setting is of paramount importance. The purpose of this review is to evaluate the incidence and factors of adhesion formation and the best preventive measures current available.

Rheumatic musculoskeletal diseases or RMD [rheumatoid arthritis (RA) and spondyloarthritis (SpA)] are systemic inflammatory diseases for which there are no biomarkers capable of predicting treatments with a higher likelihood of response in naive patients. In addition, the expiration of the anti-TNF blocking drugs’ patents has resulted in the availability of anti-TNF biosimilar drugs with the same efficacy and safety than originators but at significantly reduced prices. To guarantee a personalized therapeutic approach to RMD treatment, a board of rheumatologists and stakeholders from the Campania region, Italy, developed a clinically applicable arthritis therapeutic algorithm to guide rheumatologists (DATA project). The general methodology relied on a Delphi technique forecast to produce a set of statements that summarized the experts’ consensus. Selected clinical scenarios were discussed in light of the available evidence, and there were two rounds of voting on the therapeutic approaches. Separate discussions were held regarding rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. The decision-making factors for each disease were clinical presentation, demographics, and comorbidities. In this paper, we describe a virtuous process between rheumatologists and healthcare system stakeholders that resulted in the development of a shared therapeutic algorithm for RMD patients naive to bDMARDs.

IntroductionBrain perfusion-weighted images obtained through dynamic contrast studies play a critical and clinical role in diagnosis and treatment decisions. However, due to the patient's limited exposure to radiation, computed magnetic resonance imaging (MRI) suffers from low contrast-to-noise ratios (CNRs). Denoising MRI images is a critical task in many e-health applications for disease detection. The challenge in this research field is to define novel algorithms and strategies capable of improving accuracy and performance in terms of image vision quality and computational cost to process data. Using MRI statistical information, the authors present a method for improving image quality by combining a total variation-based denoising algorithm with histogram matching (HM) techniques.MethodsThe total variation is the Rudin–Osher–Fatemi total variation (TV-ROF) minimization approach, TV-L2, using the isotropic TV setting for the bounded variation (BV) component. The dual-stage approach is tested against two implementations of the TV-L2: the split Bregman (SB) algorithm and a fixed-point (FP) iterations scheme. In terms of HM, the study explores approximate matching and the exact histogram matching from Coltuc.ResultsAs measured by the structural similarity index (SIMM), the results indicate that in the more realistic study scenarios, the FP with an HM pairing is one of the best options, with an improvement of up to 12.2% over the one without an HM.DiscussionThe findings can be used to evaluate and investigate more advanced machine learning-based approaches for developing novel denoising algorithms that infer information from ad hoc MRI histograms. The proposed methods are adapted to medical image denoising since they account for the preference of the medical expert: a single parameter can be used to balance the preservation of (expert-dependent) relevant details against the degree of noise reduction.

Glioblastoma, the most common and heterogeneous tumor affecting brain parenchyma, is dismally characterized by a very poor prognosis. Thus, the search of new, more effective treatments is a vital need. Here, we will review the druggable epigenetic features of glioblastomas that are, indeed, currently explored in preclinical studies and in clinical trials for the development of more effective, personalized treatments. In detail, we will review the studies that have led to the identification of epigenetic signatures, IDH mutations, MGMT gene methylation, histone modification alterations, H3K27 mutations, and epitranscriptome landscapes of glioblastomas, in each case discussing the corresponding targeted therapies and their potential efficacy. Finally, we will emphasize how recent technological improvements permit to routinely investigate many glioblastoma epigenetic biomarkers in clinical practice, further enforcing the hope that personalized drugs, targeting specific epigenetic features, could be in future a therapeutic option for selected patients.

Aims: As the world population grows older, the co-existence of cancer and cardiovascular comorbidities becomes more common, complicating management of these patients. Here, we describe the impact of a large Cardio-Oncology unit in Southern Italy, characterizing different types of patients and discussing challenges in therapeutic management of cardiovascular complications. Methods and results: We enrolled 231 consecutive patients referred to our Cardio-Oncology unit from January 2015 to February 2020. Three different types were identified, according to their chemotherapeutic statuses at first visit. Type 1 included patients naïve for oncological treatments, Type 2 patients already being treated with oncological treatments, and Type 3 patients who had already completed cancer treatments. Type 2 patients presented the highest incidence of cardiovascular events (46.2% vs. 12.3% in Type 1 and 17.9% in Type 3) and withdrawals from oncological treatments (5.1% vs. none in Type 1) during the observation period. Type 2 patients presented significantly worse 48month-survival (32.1% vs. 16.7% in Type 1 and 17.9% in Type 3), and this was more evident when in the three groups we focused on patients with uncontrolled cardiovascular risk factors or overt cardiovascular disease at the first cardiologic assessment. Nevertheless, these patients showed the greatest benefit from our cardiovascular assessments, as witnessed by a small, but significant improvement in ejection fraction during follow-up (Type 2b: from 50 [20; 67] to 55 [35; 65]; P=0.04). Conclusions: Patients who start oncological protocols without an accurate baseline cardiovascular evaluation are at major risk of developing cardiac complications due to antineoplastic treatments.

Objectives To characterize patients with positive anti-topoisomerase I (ATA) in lcSSc. Methods SSc patients enrolled in the EUSTAR cohort with a disease duration of ≤3 years at database entry were considered. We assessed the risk of major organ involvement in the following groups: ATA-lcSSc vs ACA-lcSSc and vs ANA without specificity (ANA)-lcSSc, and ATA-lcSSc vs ATA-dcSSc. Cox regression models with time-dependent covariates were performed with the following outcomes: new-onset interstitial lung disease (ILD), ILD progression [forced vital capacity (FVC) decline ≥10% and ≥5% vs values at ILD diagnosis), primary myocardial involvement (PMI), pulmonary hypertension (PH), any organ involvement and all-cause mortality. Results We included 1252 patients [194 ATA-lcSSc (15.5%)], with 7.7 years (s.d. 3.5) of follow-up. ILD risk was higher in ATA-lcSSc vs ACA- and ANA-lcSSc and similar to ATA-dcSSc, although with less frequent restrictive lung disease. The risk of FVC decline ≥10% (35% of ATA-lcSSc) was lower in ATA-lcSSc than in ATA-dcSSc, whereas FVC decline ≥5% occurs similarly between ATA-lcSSc (58% of patients) and other SSc subsets, including ATA-dcSSc. The risk of PMI was similar in ATA-lcSSc and ANA-lcSSc but lower than in ACA-lcSSc; no difference in PH and mortality risk was observed among lcSSc subsets. The risk of any organ involvement, PMI and PH was lower and the mortality tended to be lower in ATA-lcSSc vs ATA-dcSSc. Conclusion ATA-lcSSc patients have a high risk of ILD, albeit with a lower risk of progression compared with ATA-dcSSc, supporting careful screening for ILD in this subgroup.

Background Excessive processing of aversive life events is a major pathology in stress-related anxiety and depressive disorders. Current pharmacological treatments have rather non-specific mechanisms of action. Somatostatin is synthesized and released as an inhibitory co-neurotransmitter by specific GABA interneurons and one of its receptors, SSTR4, is localized in brain regions involved in adaptive aversion processing and implicated in negative valence neuropathology, including the amygdala. Methods Rat and mouse experiments were conducted to investigate effects of specific SSTR4 agonism on neurobehavioral aversion processing including any normalization of stress-related hyper-responsiveness. A mouse experiment to investigate stress and SSTR4 agonism effects on reward processing was also conducted. Results In male rats (N=5-10/group) fitted with glutamate biosensors in basolateral amygdala, SSTR4 agonism attenuated glutamate release to restraint stress in control rats and particularly in rats previously exposed to chronic corticosterone. In male mice (N=10-18/group), SSTR4 agonism dose-dependently attenuated Pavlovian tone-footshock learning and memory measured as freezing behavior, both in controls (CON) and following exposure to chronic social stress (CSS) which induces excessive Pavlovian aversion learning-memory. Specificity of SSTR4 agonism effects to aversion learning-memory was demonstrated by absence of effects on discriminative reward (sucrose) learning-memory in both CON and CSS mice; SSTR4 agonism did increase reward-to-effort valuation in a dose-dependent manner, and in both CON mice and mice exposed to CSS which attenuates reward motivation. Conclusions These neuropsychopharmacological findings add substantially to the preclinical proof-of-concept evidence for SSTR4 agonism as a treatment in anxiety and depressive disorders.

Chemotherapy-induced peripheral neuropathy (CIPN) develops as a challenging nerve-damaging adverse effect of anticancer drugs used in chemotherapy. The disorder may require a chemotherapy dose reduction and a cessation of administration of chemotherapeutic drugs. Its principal sensory symptoms include, tingling, and numbness in the hands and feet. Severe pain can be encompassed among clinical manifestations. CIPN affects dramatically the patient's quality of life (QoL). Pain and sensory symptoms may occur for months, or even years after the termination of chemotherapeutic drugs. Although many pharmacological and non-pharmacological therapeutic approaches have been tested to overcome these symptoms, there is currently no standardized treatment for CIPN. According to current guidelines, Duloxetine is the only recommended agent for painful neuropathic symptoms. Therefore, finding effective therapies for CIPN is mandatory. The aim of this review was to dissect CIPN, the target and immunotherapy-based approaches to this disorder, as well as to offer new insights for new therapeutic perspectives.

Using a large sample of EU non-financial firms over the period 2008–2018, this study examines the effect of the 2014 EU Non-Financial Reporting Directive on corporate social responsibility (CSR) and finds that the Directive has led to an increase in CSR transparency and performance. Further, it shows that the association between the Directive and CSR transparency is stronger for smaller firms, firms highly followed by analysts and firms headquartered in countries with strong legal systems. The adoption of CSR reporting after the Directive’s enactment, small firm size and investments in research and development strengthen the positive effects of the Directive on CSR performance. However, the mandating of CSR reporting assurance by some EU member states seems not to have any significant impact. Lastly, our study shows that after the Directive’s enactment, firms adopting CSR reporting experienced lower systematic risk and cost of equity. Our study contributes to the debate about whether and how non-financial disclosure should be regulated and shows the positive effects of the ‘comply or explain’ approach. It also provides insights for the EU in relation to the recently approved proposal to extend CSR reporting regulation to listed small and medium-sized enterprises and mandate CSR reporting assurance.

Key components of current cybersecurity methods are the Intrusion Detection Systems (IDSs), where different techniques and architectures are applied to detect intrusions. IDSs can be based either on cross-checking monitored events with a database of known intrusion experiences, known as signature-based, or on learning the normal behavior of the system and reporting whether anomalous events occur, named anomaly-based. This work is dedicated to the application of IDS to the Internet of Things (IoT) networks, where also edge computing is used to support IDS implementation. Specific attention is given to IDSs which leverage device classification at the edge. New challenges that arise when deploying an IDS in an edge scenario are identified and remedies are proposed.

The Yarkovsky–O’Keefe–Radzievskii–Paddack (YORP) effect describes the torque induced on space objects produced by solar radiation and thermal re-emission. Previous analyses have demonstrated its influence on long-term rotational dynamics of space debris objects in Geostationary Orbit (GEO), where YORP becomes predominant with respect to other external perturbations (e.g., atmospheric drag, gravity gradient, eddy current torque), leading to a wide variety of possible behaviors. The capability of forecasting time windows of slow uniform rotation, if any, would bring significant advantages in operations of Active Debris Removal and on-orbit servicing, especially in the detumbling phase. Also, a non-negligible impact of the End-of-Life configuration, in terms of movable surfaces orientation and center of mass location, could lead to guidelines for future satellites to be easier targets in the disposal phase. In this work, a previously derived semi-analytical tumbling-averaged YORP rotational dynamics model is leveraged. Exploiting an averaged model, computational time is strongly reduced while maintaining sufficient accuracy compared to propagation of Euler’s equations of motion. First, a satellite of the Geostationary Operational Environmental Satellite (GOES) family is analyzed and compared to previous studies to verify the correct implementation of the model. A wider analysis is performed on simple geometric models, such as a box-wing satellite, a 3U CubeSat, and a rocket body. The impact of object size, surface optical properties, and center of mass position on long-term rotational behavior is investigated, providing a general insight into these phenomena with a possible future application to existing objects in GEO.

Aims The proximal tibia (PT) is the anatomical site most frequently affected by primary bone tumours after the distal femur. Reconstruction of the PT remains challenging because of the poor soft-tissue cover and the need to reconstruct the extensor mechanism. Reconstructive techniques include implantation of massive endoprosthesis (megaprosthesis), osteoarticular allografts (OAs), or allograft-prosthesis composites (APCs). Methods This was a retrospective analysis of clinical data relating to patients who underwent proximal tibial arthroplasty in our regional bone tumour centre from 2010 to 2018. Results A total of 76 patients fulfilled the inclusion criteria and were included in the study. Mean age at surgery was 43.2 years (12 to 86 (SD 21)). The mean follow-up period was 60.1 months (5.4 to 353). In total 21 failures were identified, giving an overall failure rate of 27.6%. Prosthesis survival at five years was 75.5%, and at ten years was 59%. At last follow-up, mean knee flexion was 89.8° (SD 36°) with a mean extensor lag of 18.1° (SD 24°). In univariate analysis, factors associated with better survival of the prosthesis were a malignant or metastatic cancer diagnosis (versus benign), with a five- and ten-year survival of 78.9% and 65.7% versus 37.5% (p = 0.045), while in-hospital length of stay longer than nine days was also associated with better prognosis with five- and ten-year survival rates at 84% and 84% versus 60% and 16% (p < 0.001). In multivariate analysis, only in-hospital length of stay was associated with longer survival (hazard ratio (HR) 0.23, 95% confidence interval (CI) 0.08 to 0.66). Conclusion We have shown that proximal tibial arthroplasty with endoprosthesis is a safe and reliable method for reconstruction in patients treated for orthopaedic oncological conditions. Either modular or custom implants in this series performed well. Cite this article: Bone Jt Open 2022;3(9):733–740.

Background: Since cancer pain requires complex modalities of care, the proper strategy for addressing its telemedicine-based management should be better defined. This study aimed to trace a pathway for a progressive implementation of the telemedicine process for the treatment of pain in the setting of cancer patients. Methods: The features of the model were investigated to dissect the dropout from the telemedicine pathway. A cross-sectional patient satisfaction study was conducted. The degree of satisfaction was evaluated through a developed 22-item questionnaire (Likert scale 0–7). Results: A total of 375 video consultations for 164 patients (mean age 62.9 years) were performed through remote consultations for cancer pain management between March 2021 and February 2022. After the exclusion of 72 patients, 92 (56.1%) were included in the analysis. The dropout ratio was 8.7%. The number of visits and pharmacological therapies for neuropathic pain correlated with the risk for readmission (p < 0.05). Overall, the satisfaction was very high (mean > 5.5 for all items). Conclusion: Feedback from patients reflected high satisfaction rates with the care provided. A methodological approach based on the degree of satisfaction combined with the analysis of the pathways can help to implement the quality of a service provided through telemedicine. While not without limitations, our hybrid protocol can be useful for addressing cancer pain through a patient-centered approach.

BackgroundAcute Kidney Injury (AKI) incidence has continued to rise and is recognized as a major risk factor for kidney disease progression and cardiovascular complications. Early recognition of factors associated with post-AKI complications is fundamental to stratifying patients that could benefit from closer follow-up and management after an episode of AKI. Recent studies have shown that proteinuria is a prevalent sequela after AKI and a strong predictor of complications post-AKI. This study aims to evaluate the frequency and timing of the development of de-novo proteinuria after an AKI episode in patients with known kidney function and no prior history of proteinuria.MethodsWe retrospectively analyzed data from adult AKI patients with pre- and post-kidney function information between Jan 2014 and March 2019. The presence of proteinuria determined before and after index AKI encounter was based on ICD-10 code and/or urine dipstick and UPCR during the follow-up period.ResultsOf 9697 admissions with AKI diagnoses between Jan 2014 and March 2019, 2120 eligible patients with at least one assessment of Scr and proteinuria before AKI index admission were included in the analysis. The median age was 64 (IQR 54-75) years, and 57% were male. 58% (n-1712) patients had stage 1 AKI, 19% (n = 567) stage 2 AKI, and 22% (n = 650) developed stage 3 AKI. De novo proteinúria was found in 62% (n = 472) of patients and was already present by 90 days post-AKI in 59% (209/354). After adjusting for age and comorbidities, severe AKI (stage 2/3 AKI) and diabetes, were independently associated with increased risk for De novo proteinuria.ConclusionSevere AKI is an independent risk factor for subsequent de novo proteinuria post-hospitalization. Further prospective studies are needed to determine whether strategies to detect AKI patients at risk of proteinuria and early therapeutics to modify proteinuria can delay the progression of kidney disease.

Cell identity is determined by chromatin structure and the profiles of gene expression, which are dependent on chromatin accessibility and DNA methylation of regions critical for gene expres-sions, such as enhancers and promoters. These epigenetic modifications are required for mamma-lian development and are essential for the establishment and the maintenance of the cellular iden-tity. DNA methylation was once thought to be a permanent repressive epigenetic mark, but sys-tematic analysis in various genomic contexts reveals a more dynamic regulation than previously thought. In fact, both active DNA methylation and demethylation occur during cell fate commit-ment and terminal differentiation. To link methylation signatures of specific genes to their ex-pression profiles, we have determined the methyl-CpG configurations of the promoters of five genes switched on and off during murine postnatal brain differentiation by bisulfite-targeted se-quencing. We report here the structure of significant, dynamic and stable methyl-CpG profiles as-sociated with silencing or activation of expression of genes during brain postnatal differentiation. Strikingly, these methylation cores mark different mouse brain areas and cell types derived from the same areas during postnatal differentiation.

Blood lead (Pb) level (BLL) is a commonly used biomarker to evaluate associations with health effects. However, interventions to reduce the adverse effects of Pb require relating BLL to external exposure. Moreover, risk mitigation actions need to ensure protection of more susceptible individuals with a greater tendency to accumulate Pb. Because little data is available to quantify inter-individual variability in biokinetics of Pb, we investigated the influence of genetics and diet on BLL in the genetically diverse Collaborative Cross (CC) mouse population. Adult female mice from 49 CC strains received either a standard mouse chow or a chow mimicking the American diet while being provided water ad libitum with 1000 ppm Pb for 4 weeks. In both arms of the study, inter-strain variability was observed; however, in American diet-fed animals, the BLL was greater and more variable. Importantly, the degree of variation in BLL among strains on the American diet was greater (2.3) than the default variability estimate (1.6) used in setting the regulatory standards. Genetic analysis identified suggestive diet-associated haplotypes that were associated with variation in BLL, largely contributed by the PWK/PhJ strain. This study quantified the variation in BLL that is due to genetic background, diet, and their interactions, and observed that it may be greater than that assumed for current regulatory standards for Pb in drinking water. Moreover, this work highlights the need of characterizing inter-individual variation in BLL to ensure adequate public health interventions aimed at reducing human health risks from Pb.

Talaromycosis, a severe and invasive fungal infection caused byTalaromyces marneffei, is difficult to treat and impacts those living in endemic regions of southeast Asia, India, and China. While 30% of infections result in mortality, our understanding of the genetic basis of pathogenesis for this fungus is limited. To address this, we apply population genomics and genome wide association study approaches to a cohort of 336T. marneffeiisolates collected from patients who enrolled in the Itraconazole versus Amphotericin B for Talaromycosis (IVAP) trial in Vietnam. We find that isolates from northern and southern Vietnam form two distinct geographical clades, with isolates from southern Vietnam associated with increased disease severity. Leveraging longitudinal isolates, we identify multiple instances of disease relapse linked to unrelated strains, highlighting the potential for multi-strain infections. In more frequent cases of persistent talaromycosis caused by the same strain, we identify variants arising over the course of patient infections that impact genes predicted to function in the regulation of gene expression and secondary metabolite production. By combining genetic variant data with patient metadata for all 336 isolates, we identify pathogen variants significantly associated with multiple clinical phenotypes. In addition, we identify genes and genomic regions under selection across both clades, highlighting loci undergoing rapid evolution, potentially in response to external pressures. With this combination of approaches, we identify links between pathogen genetics and patient outcomes and identify genomic regions that are altered duringT. marneffeiinfection, providing an initial view of how pathogen genetics affects disease outcomes.

Funding Acknowledgements Type of funding sources: None. Background/Introduction Transthyretin cardiac amyloidosis (ATTR-CA) is associated with an increased incidence of arrhythmias. We hypothesized that non-invasive, two-week outpatient cardiac rhythm monitoring of patients with ATTR-CA would detect high rates of ventricular tachycardia and atrial fibrillation/flutter (AF). Purpose To characterize arrhythmia in patients with ATTR-CA on two-week, non-invasive cardiac rhythm monitors. Methods 38 patients with ATTR-CA (mean age 76.9 SD 10.0 years, 89.5% male) who underwent two-week remote external patch monitoring were included in this single center retrospective study. An age-matched control group included 38 patients (mean age 73.9 SD 12.3, 76.3% male) who underwent the same cardiac rhythm monitoring as part of neurological workups. Results NSVT was detected on the remote monitor in 81.6% of ATTR-CA patients and AF was detected in 26.3% of patients. ATTR-CA was associated with higher rates of NSVT and AF compared to the control group (28.9% with NSVT and 5.3% with AF). As seen in Figure 1, there were only three ATTR-CA patients without either AF, NSVT, advanced atrioventricular block, or a significant pause detected on remote monitor. Among the ATTR-CA group, at median 45 weeks follow-up, there were 4 heart failure hospitalizations, 2 cardiovascular events (1 episode of sustained VT and 1 stroke), 6 permanent pacemakers placed, and 3 implantable cardioverter-defibrillators placed, including one for sustained VT. NSVT and AF were not associated with a composite of these adverse outcome. Conclusion ATTR-CA was associated with high rates of NSVT and AF on noninvasive remote monitors. While evidence regarding the management of arrhythmias, particularly NSVT/VT, in ATTR-CA remains limited, two-week noninvasive cardiac monitoring can be considered to aid in risk stratification for both atrial and ventricular arrhythmias in ATTR-CA.