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Abstract Background Visits to Emergency Departments (ED) can be traumatic for Nursing Home (NH) residents. In Italy, the rate of ED visits by NH residents was recently calculated as 3.3%. The reduction of inappropriate ED visits represents a priority for National Healthcare Systems worldwide. Nevertheless, research on factors associated with ED visits is still under-studied in the Italian setting. This study has two main aims: (i) to describe the baseline characteristics of NH residents visiting ED at regional level; (ii) to assess the characteristics, trends, and factors associated with these visits. Methods A retrospective study of administrative data for five years was performed in the Piedmont Region. Data from 24,208 NH residents were analysed. Data were obtained by merging two ministerial databases of residential care and ED use. Sociodemographic and clinical characteristics of the residents, trends, and rates of ED visits were collected. A Generalized Linear Model (GLM) regression was used to evaluate the factors associated with ED visits. Results In 5 years, 12,672 residents made 24,609 ED visits. Aspecific symptoms (45%), dyspnea (17%) and trauma (16%) were the most frequent problems reported at ED. 51% of these visits were coded as non-critical, and 58% were discharged to the NH. The regression analysis showed an increased risk of ED visits for men (OR = 1.61, 95% CI 1.51–1.70) and for residents with a stay in NH longer than 400 days (OR = 2.19, 95% CI 2.08–2.31). Conclusions Our study indicates that more than half of NH residents’ ED visits could potentially be prevented by treating residents in NH. Investments in the creation of a structured and effective network within primary care services, promoting the use of health technology and palliative care approaches, could reduce ED visits and help clinicians manage residents on-site and remotely.

IntroductionThe COVID-19 pandemic led to a significant reorganization of health services, potentially affecting the quality of care for major public health concerns such as proximal femoral fractures. This study aimed to investigate potential changes in the timing of various steps in the patient journey after a hip fracture during the pandemic in Piedmont, a region in Northern Italy.MethodsA retrospective study was conducted on the discharge records of patients aged 65 or older who were admitted for hip surgery following a femur fracture in 2019 and 2020. The study examined four-time steps: duration from hospital admission to surgery, length of hospital stay, interval between hospital discharge and admission to the rehabilitation facility, and duration of stay at the rehabilitation facility. To mitigate biases linked to sex and age factors, groups well-balanced across 2019 and 2020 were created using propensity score estimation.ResultsThe dataset consisted of two cohorts of 583 patients each for the years 2019 and 2020. The average duration from admission to surgery was approximately 1.9 days in both years, with 75% of patients undergoing surgery within 2 days of hospital admission. The average hospital stay reduced from 13.49 days in 2019 to 11.34 days in 2020. The gap between hospital discharge and admission to rehabilitation was approximately 10-12 days, and the average duration of stay at the rehabilitation facility was about 31.6 days.DiscussionThe study indicates that healthcare systems can exhibit resilience and adaptability, even during a global pandemic, to ensure high-quality and safe standards of care. However, further long-term studies are needed to fully understand the pandemic's impact on primary health outcomes following hip replacement surgery and subsequent rehabilitation. The potential role of telemedicine in reducing the time between steps also warrants further investigation.

IntroductionThe COVID-19 pandemic has resulted in numerous deaths, great suffering, and significant changes in people's lives worldwide. The introduction of the vaccines was a light in the darkness, but after 18 months, a great disparity in vaccination coverage between countries has been observed. As disparities in vaccination coverage have become a global public health issue, this study aimed to analyze several variables to identify possible determinants of COVID-19 vaccination.MethodsAn ecological study was conducted using pooled secondary data sourced from institutional sites. A total of 205 countries and territories worldwide were included. A total of 16 variables from different fields were considered to establish possible determinants of COVID-19 vaccination: sociodemographic, cultural, infrastructural, economic and political variables, and health system performance indicators. The percentage of the population vaccinated with at least one dose and the total doses administered per 100 residents on 15 June 2022 were identified as indicators of vaccine coverage and outcomes. Raw and adjusted values for delivered vaccine doses in the multivariate GLM were determined using R. The tested hypothesis (i.e., variables as determinants of COVID-19 vaccination) was formulated before data collection. The study protocol was registered with the grant number NCT05471635.ResultsGDP per capita [odds = 1.401 (1.299–1.511) CI 95%], access to electricity [odds = 1.625 (1.559–1.694) CI 95%], political stability, absence of violence/terrorism [odds = 1.334 (1.284–1.387) CI 95%], and civil liberties [odds = 0.888 (0.863–0.914) CI 95%] were strong determinants of COVID-19 vaccination. Several other variables displayed a statistically significant association with outcomes, although the associations were stronger for total doses administered per 100 residents. There was a substantial overlap between raw outcomes and their adjusted counterparts.DiscussionThis pioneering study is the first to analyze the association between several different categories of indicators and COVID-19 vaccination coverage in a wide complex setting, identifying strong determinants of vaccination coverage. Political decision-makers should consider these findings when organizing mass vaccination campaigns in a pandemic context to reduce inequalities between nations and to achieve a common good from a public health perspective.

Background The association between timing of integrated home palliative care (IHPC) enrolment and emergency department (ED) visits is still under debate, and no studies investigated the effect of the timing of IHPC enrolment on ED visits, according to their level of emergency. This study aimed to investigate the impact of the timing of IHPC enrolment on different acuity ED visits.Methods A retrospective, pre-/post-intervention study was conducted from 2013 to 2019 in Italy. Analyses were stratified by IHPC duration (short ≤30 days; medium 31-90 days; long >90 days) and triage tags (white/green: low level of emergency visit; yellow/red: medium-to-high level). The impact of the timing of IHPC enrolment was evaluated in two ways: incidence rate ratios (IRRs) of ED visits were determined (1) before and after IHPC enrolment in each group and (2) post-IHPC among groups.Results A cohort of 17 983 patients was analysed. Patients enrolled early in the IHPC programme had a significantly lower incidence rate of ED visits than the pre-enrolment period (IRR = 0.65). The incidence rates of white/green and yellow/red ED visits were significantly lower post-IHPC enrolment for patients enrolled early (IRR = 0.63 and 0.67, respectively). All results were statistically significant (P < .001). Comparing the IHPC groups after enrolment versus the short group, medium and long IHPC groups had a significant reduction of ED visits (IRR = 0.37, IRR = 0.14 respectively), showing a relation between the timing of IHPC enrolment and the incidence of ED visits. A similar trend was observed after accounting for triage tags of ED visits.Conclusion The timing of IHPC enrolment is related with a variation of the incidence of ED visits. Early IHPC enrolment is related to a high significant reduction of ED visits when compared to the 90-day pre-IHPC enrolment period and to late IHPC enrolment, accounting for both low-level and medium-to-high level emergency ED visits.

Background After a pneumonia outbreak in late 2019 in China, a new virus related to the Coronaviridae strain, called Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), was identified as the pathogen of an emerging disease known as COronaVIrus Disease 19 (COVID-19). Preliminary evidence outlines a higher prevalence in adults and lower susceptibility in children. However, recent epidemiologic research highlighted that transmissibility and susceptibility among children and adolescents become higher due to new virus variants. Infections among youth arises with mainly respiratory and gastrointestinal symptoms and malaise. Nevertheless, critical illness affects new-borns and fragile children, requiring hospitalization and possibly intensive care support. Aim of this study was to examine the impact of COVID-19 pandemic on hospital admissions among children and adolescents aged 0 to 17 years over three waves of COVID-19 (from February 2020 to May 2021) in Piedmont, a large Italian region, and to investigate the possible determinants of hospitalizations. Methods A meta-analysis for risk assessment was performed over three waves of COVID-19 (from February 2020 to May 2021). Data were extracted from the official Italian National Information System and ISTAT. Results Overall, 442 paediatric patients were enrolled and admissions concerned mostly the age group 0–4 years (60.2%). Trends of hospitalization showed a slight increase of paediatric admissions already in March 2020 and a rise during second and third waves (November 2020, March 2021). Paediatric age-grouped hospitalizations (0–4; 12–17; 5–11) reproduced an analogous trend. The children and adolescent hospitalization rate appeared lower than overall population with a moderate slope of increase in comparison with population slope. Monthly hospitalization rate (per 100,000) of children and adolescents aged 0–17 years reproduced the increasing trend of hospitalization numbers. This trend was influenced, in particular, by the trend of hospitalization rates for children aged 0–4 years. The meta-analysis for risk assessment showed a decreased likelihood of rescue of hospitalizations in female, 5–11 and 12–17 age groups. Conversely, the meta-analysis showed a positive association between foreign nationality and hospitalizations. Conclusions Our results show a comparable trend of paediatric hospital admissions for COVID-19 and of the entire population hospitalizations over three waves. COVID-19 hospital admissions increase with a bimodal age distribution and the most admissions are among patients aged ≤4 or 5–11 years. Significant predictive factors of hospitalization are identified.

Text-to-image synthesis is one of the most critical and challenging problems of generative modeling. It is of substantial importance in the area of automatic learning, especially for image creation, modification, analysis and optimization. A number of works have been proposed in the past to achieve this goal; however, current methods still lack scene understanding, especially when it comes to synthesizing coherent structures in complex scenes. In this work, we propose a model called CapGAN, to synthesize images from a given single text statement to resolve the problem of global coherent structures in complex scenes. For this purpose, skip-thought vectors are used to encode the given text into vector representation. This encoded vector is used as an input for image synthesis using an adversarial process, in which two models are trained simultaneously, namely: generator (G) and discriminator (D). The model G generates fake images, while the model D tries to predict what the sample is from training data rather than generated by G. The conceptual novelty of this work lies in the integrating capsules at the discriminator level to make the model understand the orientational and relative spatial relationship between different entities of an object in an image. The inception score (IS) along with the Fréchet inception distance (FID) are used as quantitative evaluation metrics for CapGAN. IS recorded for images generated using CapGAN is 4.05 ± 0.050, which is around 34% higher than images synthesized using traditional GANs, whereas the FID score calculated for synthesized images using CapGAN is 44.38, which is ab almost 9% improvement from the previous state-of-the-art models. The experimental results clearly demonstrate the effectiveness of the proposed CapGAN model, which is exceptionally proficient in generating images with complex scenes.

Abstract Background Emergency department (ED) use among nursing home (NH) residents is an internationally-shared issue that is understudied in Italy. The long term care in Italy is part of the health system. This study aimed to assess trajectories of ED use among NH residents and determinants between demographic, health supply, clinical/functional factors. Methods A pooled, cross-sectional, time series analysis was performed in an Italian region in 2012/2019. The analysis measured the trend of ED user percentages associated with chronic conditions identified at NH admission. A GLM multivariate model was used to evaluate determinants of ED use. The variables collected were sex, age, assistance intensity, destination after discharge from NH, chronic conditions at NH admission, need for daily life assistance, degree of mobility, cognitive impairments, behavioural disturbances and were taken from two databases of the official Italian National Information System (FAR and C2 registries) that were combined to create a unique and anonymous code for each patient. Results A total of 37,311 residents were enrolled; 55.75% (20,800 residents) had at least one ED visit. The majority of the residents had cardiovascular (25.99%) or mental diseases (24.37%). In all pathologies, the percentage of ED users decreased and the decrease accelerated over time. These results were confirmed in the fixed effects regression model (coefficient for linear term (b = − 3.6177, p = 0, 95% CI = [− 5.124, − 2.1114]); coefficient for quadratic term = − 0.7691, p = 0.0046, 95% CI = [− 1.2953, − 0.2429]). Analysis showed an increased odds of ED visits involving males (OR = 1.27, 95% CI 1.24;1.30) and patients affected by urogenital diseases (OR = 1.16, 95% CI [1.031–1.314]). The lowest odds of ED visits were observed among subjects aged > 90 years (OR = 0.64, 95% CI [0.60–0.67]), who required assistance for their daily life activities (OR = 0.86; 95% CI = [0.82, 0.91]), or with serious cognitive disturbances (OR = 0.86; 95% CI = [0.84, 0.89]), immobile (OR = 0.93; 95% CI = [0.89, 0.96]), or without behavioural disturbances (OR = 0.92; 95% CI = [0.90, 0.94]). Conclusions The percentage of ED users has decreased, through support from the Italian disciplinary long-term care system. The demographic, clinical/functional variables associated with ED visits in this study will be helpful to develop targeted and tailored interventions to avoid unnecessary ED use.

BackgroundAllowing patients to remain at home and decreasing the number of unnecessary emergency room visits have become important policy goals in modern healthcare systems. However, the lack of available literature makes it critical to identify determinants that could be associated with increased emergency department (ED) visits in patients receiving integrated home care (IHC).MethodsA retrospective observational study was carried out in a large Italian region among patients with at least one IHC event between January 1, 2012 and December 31, 2017. IHC is administered from 8 am to 8 pm by a team of physicians, nurses, and other professionals as needed based on the patient’s health conditions. A clinical record is opened at the time a patient is enrolled in IHC and closed after the last service is provided. Every such clinical record was defined as an IHC event, and only ED visits that occurred during IHC events were considered. Sociodemographic, clinical and IHC variables were collected. A multivariate, stepwise logistic analysis was then performed, using likelihood of ED visit as a dependent variable.ResultsA total of 29 209 ED visits were recorded during the 66 433 IHC events that took place during the observation period. There was an increased risk of ED visits in males (odds ratio [OR] = 1.29), younger patients, those with a family caregiver (OR = 1.13), and those with a higher number of cohabitant family members. Long travel distance from patients’ residence to the ED reduced the risk of ED visits. The risk of ED visits was higher when patients were referred to IHC by hospitals or residential facilities, compared to referrals by general practitioners. IHC events involving patients with neoplasms (OR = 1.91) showed the highest risk of ED visits.ConclusionEvidence of sociodemographic and clinical determinants of ED visits may offer IHC service providers a useful perspective to implement intervention programmes based on appropriate individual care plans and broad-based client assessment.

Background: Integrated palliative home care (IHPC) is delivered to patients with progressive end-stage diseases. During the COVID-19 pandemic, IHPC needed to provide high-quality home care services for patients who were treated at home, with the goal of avoiding unnecessary care, hospital admissions, and emergency department (ED) visits. This study aimed to compare the ED visits of IHPC recipients in a large Italian region before and during the first two waves of the COVID-19 pandemic and to find sociodemographic or clinical characteristics associated with changes in ED visits during the first two waves of COVID-19 pandemic, compared with the period before. Methods: Administrative databases were used to identify sociodemographic and clinical variables of IHPC recipients admitted before and during the pandemic. The obtained data were balanced by applying a propensity score. The average number of ED visits before and during the pandemic was calculated by using the Welch’s t test and stratified by all the variables. Results: Before and during the pandemic, 5155 and 3177 recipients were admitted to IHPC, respectively. These individuals were primarily affected by neoplasms. ED visits of IHPC recipients reduced from 1346 to 467 before and during the pandemic, respectively. A reduced mortality among IHCP patients who had at least one ED visit during the pandemic (8% during the pandemic versus 15% before the pandemic) was found. The average number of ED visits decreased during the pandemic [0.143, confidence interval (CI) = (0.128–0.158) versus 0.264, CI = (0.242–0.286) before the pandemic; p < 0.001] for all ages and IHPC duration classes. The presence of a formal caregiver led to a significant decrease in ED use. Medium and high emergency ED admissions showed no difference, whereas a decrease in low-level emergency ED admissions during the pandemic [1.27, CI = (1.194–1.345) versus 1.439, CI = (1.3–1.579) before the pandemic; p = 0.036] was found. Conclusion: ED visits among IHPC recipients were significantly decreased during the first two waves of the COVID-19 pandemic, especially in those individuals characterized by a low level of emergency. This did not result in an increase in mortality among IHPC recipients. These findings could inform the reorganization of home care services after the pandemic.

Ontogenesis is the development of an organism from its earliest stage to maturity, including homeostasis maintenance throughout adulthood despite environmental perturbations. Almost all cells of a multicellular organism share the same genomic information. Nevertheless, phenotypic diversity and complex supra-cellular architectures emerge at every level, starting from tissues and organs. This is possible thanks to a robust and dynamic interplay of regulative mechanisms.To study ontogenesis, it is necessary to consider different levels of regulation, both genetic and epigenetic. Each cell undergoes a specific path across a landscape of possible regulative states affecting both its structure and its functions during development. This paper proposes using the Nets-Within-Nets formalism, which combines Petri Nets’ simplicity with the capability to represent and simulate the interplay between different layers of regulation connected by non-trivial and context-dependent hierarchical relations.In particular, this work introduces a modeling strategy based on Nets-Within-Nets that can model several critical processes involved in ontogenesis. Moreover, it presents a case study focusing on the first phase of Vulval Precursor Cells specification in C.Elegans. The case study shows that the proposed model can simulate the emergent morphogenetic pattern corresponding to the observed developmental outcome of that phase, in both the physiological case and different mutations. The model presented in the results section is available online at https://github.com/sysbio-polito/NWN_CElegans_VPC_model/

Abstract Background Current policies recommend integrating home care and palliative care to enable patients to remain at home and avoid unnecessary hospital admission and emergency department (ED) visits. The Italian health care system had implemented integrated palliative home care (IHPC) services to guarantee a comprehensive, coordinated approach across different actors and to reduce potentially avoidable ED visits. This study aimed to analyze the trajectories of ED visit rates among patients receiving IHPC in the Italian healthcare system, as well as the association between socio-demographic, health supply, and clinical factors. Methods A pooled, cross-sectional, time series analysis was performed in a large Italian region in the period 2013–2017. Data were taken from two databases of the official Italian National Information System: Home Care Services and ED use. A clinical record is opened at the time a patient is enrolled in IHPC and closed after the last service is provided. Every such clinical record was considered as an IHPC event, and only ED visits that occurred during IHPC events were considered. Results The 20,611 patients enrolled in IHPC during the study period contributed 23,085 IHPC events; ≥1 ED visit occurred during 6046 of these events. Neoplasms accounted for 89% of IHPC events and for 91% of ED visits. Although there were different variations in ED visit rates during the study period, a slight decline was observed for all diseases, and this decline accelerated over time (b = − 0.18, p = 0.796, 95% confidence interval [CI] = − 1.59;1.22, b-squared = − 1.25, p

Abstract Background The paper aims to describe the 3-year incidence (2015/17) of aggressive acts against all healthcare workers to identify risk factors associated to violence among a variety of demographic and professional determinants of assaulted, and risk factors related to the circumstances surrounding these events. Methods A retrospective observational study of all 10,970 health workers in a large-sized Italian university hospital was performed. The data, obtained from the “Aggression Reporting Form”, which must be completed by assaulted workers within 72 h of aggression, were collected for the following domains: worker assaulted (sex, age class, years worked); profession (nurses, medical doctors, non-medical support staff, administrative staff, midwives); aggressive acts (activity type during aggressive acts, season, time and location of aggressive acts); and type of aggressive acts (verbal, non-verbal, consequences, aggressors). Results Three hundred sixty-four (3.3%) workers experienced almost one aggression. The majority of the assaulted workers were female (77.5%), had worked for 6/15 years and were Nurses (64.3%). The majority of aggressive acts occurred during assistance and patient care (38.2%), in the spring and during the afternoon/morning shifts and took place in locations where patients were present (47.3%). The most prevalent aggression type was verbal (76.9%). The patient was the most common aggressor (46.7%). 56% of those assaulted experienced interruptions in their work. Being female, being

Abstract Background The Critical Assessment of Functional Annotation (CAFA) is an ongoing, global, community-driven effort to evaluate and improve the computational annotation of protein function. Results Here, we report on the results of the third CAFA challenge, CAFA3, that featured an expanded analysis over the previous CAFA rounds, both in terms of volume of data analyzed and the types of analysis performed. In a novel and major new development, computational predictions and assessment goals drove some of the experimental assays, resulting in new functional annotations for more than 1000 genes. Specifically, we performed experimental whole-genome mutation screening in Candida albicans and Pseudomonas aureginosa genomes, which provided us with genome-wide experimental data for genes associated with biofilm formation and motility. We further performed targeted assays on selected genes in Drosophila melanogaster, which we suspected of being involved in long-term memory. Conclusion We conclude that while predictions of the molecular function and biological process annotations have slightly improved over time, those of the cellular component have not. Term-centric prediction of experimental annotations remains equally challenging; although the performance of the top methods is significantly better than the expectations set by baseline methods in C. albicans and D. melanogaster, it leaves considerable room and need for improvement. Finally, we report that the CAFA community now involves a broad range of participants with expertise in bioinformatics, biological experimentation, biocuration, and bio-ontologies, working together to improve functional annotation, computational function prediction, and our ability to manage big data in the era of large experimental screens.

On March 11, 2020, the World Health Organization (WHO) has officially declared the novel coronavirus outbreak a pandemic. The national governments deployed a series of severe control measures and a set of public health policies in order to stop the spread of COVID-19 pandemic. The aim of this study is to investigate the correlation between specific interventions and incident cases during the second wave in multiple and specific countries. The observational study was based on data from the Oxford COVID-19 Government Response Tracker (OxCGRT) source retrieved from October 1st, 2020 to January 10, 2021. Thirteen specific indicators related to measures adopted were considered. Four European countries were taken into account: Italy, German, Spain and UK. A vector autoregression (VAR) model and the Granger Causality test were performed to allow for an assessment of any possible effect induced by each control measure against the overall pandemic growth. Wald test was conducted to compute p-values. No correlation between the applied measures and incident cases in the four countries was shown by the Granger causality test. Only closings of workplaces (C2) and limits on private gatherings showed (C4) a significant correlation with incident cases in UK and restrictions on internal movement between cities/regions in Germany. The Granger causality also tested that C2 and C4 forecasted the decrease of incident cases after a time lag of 6–30 days in UK and Germany, respectively. Policy makers must analyze the context in which policies are set because of effectiveness of interventions can be influenced by local context and, especially, by socio-economic and demographic characteristics, and make a proper communication to support the resilience of the population capable of guaranteeing adherence to the interventions implemented.

The enzyme nicotinate phosphoribosyltransferase (NAPRT) mediates the rate-limiting step in NAD salvage pathway starting from nicotinic acid. Here the authors show that NAPRT can be detected extracellularly, binds to Toll like receptor 4, and activates NF-kB signaling and cytokine production in macrophage via NAD synthesis-independent pathways.

Objective To assess the determinants of ED use in paediatric patients enrolled in an Integrated Paediatric Home Care (IPHC) program. Methods A retrospective study was conducted using administrative databases on a cohort of patients enrolled in an IPHC program between January 1st, 2012, and December 31st, 2017, in Northern Italy. ED visits that occurred during the IPHC program were considered. Data were collected considering sociodemographic, clinical and organizational variables. A multivariable stepwise logistic regression analysis was performed. The dependent variable to identify possible associations was ED visit. Results A total of 463 ED visits occurred in 465 children, with an incidence rate of 1. The risk of ED visits significantly increased among children involved in the IPHC program after hospital discharge (OR 1.94). Additionally, the risk of ED visits increased significantly as the duration of IPHC increased (OR 5.80 between 101 and 200 days, to OR 7.84 between 201 and 300 days, OR 12.54 between 301 and 400 days and OR 18.67 to more than 400 days). Conclusion The overall results represent a practical perspective to contribute improving both the service quality of IPHC and reducing low acuity and improper ED use.

Background and Methods: Long non-coding RNAs (LncRNAs) and microRNAs are involved in the pathogenesis of obesity, a multifactorial disease that is characterized by inflammation, cardiometabolic complications, and increased cancer risk among other co-morbidities. The up/down regulation of LncRNAs and microRNAs may play an important role in this condition to identify new diagnostic/prognostic markers. The aim of the study was to identify circulating inflammatory LncRNAs in obese adolescents (n = 54) and to evaluate whether their expression behaved differently compared to normal-weight adolescents (n = 26). To have a more complete insight, the expression of some circulating miRNAs that are linked to obesity (miR-33a, miR-223, miR-142, miR-199a, miR-181a, and miR-4454) were also analyzed. Results: LncRNAs and miRNAs were extracted simultaneously from plasma samples and amplified by Real-Time PCR. Among the 86 LncRNAs that were analyzed with custom pre-designed plates, only four (RP11-347E10.1, RP11-10K16.1, LINC00657, and SNHG12) were amplified in both normal-weight and obese adolescents and only SNHG12 showed significantly lower expression compared to the normal-weight adolescents (p = 0.026). Circulating miRNAs showed a tendency to increase in obese subjects, except for miR-181a expression. LncRNAs and miRNAs correlated with some clinical and metabolic parameters. Conclusions: Our results suggest the importance of these new biomarkers to better understand the molecular mechanisms of childhood obesity and its metabolic disorder.

During these days of global emergency for the COVID-19 disease outbreak, there is an urgency to share reliable information able to help worldwide life scientists to get better insights and make sense of the large amount of data currently available. In this study we used the results presented in [1] to perform two different Systems Biology analyses on the HCoV-host interactome. In the first one, we reconstructed the interactome of the HCoV-host proteins, integrating it with highly reliable miRNA and drug interactions information. We then added the IL-6 gene, identified in recent publications [2] as heavily involved in the COVID-19 progression and, interestingly, we identified several interactions with the reconstructed interactome. In the second analysis, we performed a Gene Ontology and a Pathways enrichment analysis on the full set of the HCoV-host interactome proteins and on the ones belonging to a significantly dense cluster of interacting proteins identified in the first analysis. Results of the two analyses provide a compact but comprehensive glance on some of the current state-of-the-art regulations, GO, and pathways involved in the HCoV-host interactome, and that could support all scientists currently focusing on SARS-CoV-2 research.

Epigenetic changes, including miRNAs deregulation, have been suggested to play a significant role in development of obliterative bronchiolitis (OB) in transplanted lungs. Many studies have tried to identify ideal candidate miRNAs and the downstream pathways implicated in the bronchiolar fibro-obliterative process. Several candidate miRNAs, previously indicated as possibly being associated with OB, were analyzed by combining the quantitative real time-polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH) of lung tissues of OB affected patients. Disease and OB-lesion-specific expression of miR-21-5p was confirmed and by computational analysis we were able to identify the network of genes most probably associated miR-21-5p in the context of OB fibrogenesis. Among all potentially associated genes, STAT3 had a very high probability score. Immunohistochemistry showed that STAT3/miR-21-5p were co-over expressed in OB lesions, thus, suggesting miR-21-5p could regulate STAT3 expression. However, miR-21-5p inhibition in cultures of bronchiolitis obliterans syndrome (BOS) derived myofibroblasts did not significantly affect STAT3 mRNA and protein expression levels. This study demonstrates the specificity of miR-21-5p over-expression in OB lesions and contributes to existing knowledge on the miR-21-5p downstream pathway. Activation of STAT3 is associated with miR-21-5p upregulation, however, STAT-3 network activation is most likely complex and miR-21-5p is not the sole regulator of STAT3.

With next-generation sequencing, the genomic data available for the characterization of integration sites (IS) has dramatically increased. At present, in a single experiment, several thousand viral integration genome targets can be investigated to define genomic hot spots. In a previous article, we renovated a formal CIS analysis based on a rigid fixed window demarcation into a more stretchy definition grounded on graphs. Here, we present a selection of supporting data related to the graph-based framework (GBF) from our previous article, in which a collection of common integration sites (CIS) was identified on six published datasets. In this work, we will focus on two datasets, ISRTCGD and ISHIV, which have been previously discussed. Moreover, we show in more detail the workflow design that originates the datasets.

Medication discrepancies are defined as unexplained differences among regimens across different sites of care. The problem of medication discrepancies that occur during the entire care pathway from hospital admission to a local care setting discharge (namely all types of settings dedicated to formal care other than hospitals) has received little attention in the medical literature. The present study aims to (1) determine the prevalence of medication discrepancies that occur during the entire care pathway from hospital admission to local care setting discharge, (2) describe the discrepancy and medication type, and (3) identify potential risk factors for experiencing medication discrepancies in patient care transitions. Evidence from an integrated health care system, such as the Italian one, may explain results from other studies in different healthcare systems.A retrospective longitudinal cohort study of patients admitted from July 2015 to July 2016 to the Giovanni Bosco Hospital serving Turin, Italy and its surrounding territory was performed. Discrepancies were recorded at the following four care transitions: T1: Hospital admission; T2: Hospital discharge; T3: Admission into local care settings; T4: Discharge from local care settings. All evaluations were based on documented regimens and were performed by a team (doctor, nurse and pharmacists).Of 366 included patients, 25.68% had at least one discrepancy. The most frequent type of discrepancy was from medication omission (N = 74; 71.15%). Only discharge from a long-stay care setting (T4) was significantly associated with the onset of discrepancies (p = 0.045). When considering a lack of adequate documentation, not as missing data but as a discrepancy, 43.72% of patients had at least one discrepancy.This study suggests that an integrated health care system, such as Italian system, may influence the prevalence of discrepancies, thus highlighting the need for structured multidisciplinary and, if possible, computerized medication reconciliation to prevent medication discrepancies and improve the quality of medical documentation.

To analyze absenteeism among healthcare workers (HCWs) at a large Italian hospital and to estimate the increase in absenteeism that occurred during seasonal flu periods.Retrospective observational study.The absenteeism data were divided into three "epidemic periods," starting at week 42 of one year and terminating at week 17 of the following year (2010-2011, 2011-2012, 2012-2013), and three "non-epidemic periods," defined as week 18 to week 41 and used as baseline data. The excess of the absenteeism occurring among HCWs during periods of epidemic influenza in comparison with baseline was estimated. All data, obtained from Hospital's databases, were collected for each of the following six job categories: medical doctors, technical executives (i.e., pharmacists), nurses and allied health professionals (i.e., radiographers), other executives (i.e., engineers), nonmedical support staff, and administrative staff. The HCWs were classified by: in and no-contact; vaccinated and unvaccinated.5,544, 5,369, and 5,291 workers in three years were studied. The average duration of absenteeism during the epidemic periods increased among all employees by +2.07 days/person (from 2.99 to 5.06), and the relative increase ranged from 64-94% among the different job categories. Workers not in contact with patients experienced a slightly greater increase in absenteeism (+2.28 days/person, from 2.73 to 5.01) than did employees in contact with patients (+2.04, from 3.04 to 5.08). The vaccination rate among HCWs was below 3%, however the higher excess of absenteeism rate among unvaccinated in comparison with vaccinated workers was observed during the epidemic periods (2.09 vs 1.45 days/person).The influenza-related absenteeism during epidemic periods was quantified as totaling more than 11,000 days/year at the Italian hospital studied. This result confirms the economic impact of sick leave on healthcare systems and stresses on the necessity of encouraging HCWs to be immunized against influenza.

The pathogenesis of Bronchiolitis Obliterans Syndrome (BOS), the main clinical phenotype of chronic lung allograft dysfunction, is poorly understood. Recent studies suggest that epigenetic regulation of microRNAs might play a role in its development. In this paper we present the application of a complex computational pipeline to perform enrichment analysis of miRNAs in pathways applied to the study of BOS. The analysis considered the full set of miRNAs annotated in miRBase (version 21), and applied a sequence of filtering approaches and statistical analyses to reduce this set and to score the candidate miRNAs according to their potential involvement in BOS development. Dysregulation of two of the selected candidate miRNAs-miR-34a and miR-21 -was clearly shown in in-situ hybridization (ISH) on five explanted human BOS lungs and on a rat model of acute and chronic lung rejection, thus definitely identifying miR-34a and miR-21 as pathogenic factors in BOS and confirming the effectiveness of the computational pipeline.

One of the biggest challenges in the study of biological regulatory mechanisms is the integration, americanmodeling, and analysis of the complex interactions which take place in biological networks. Despite post transcriptional regulatory elements (i.e., miRNAs) are widely investigated in current research, their usage and visualization in biological networks is very limited. Regulatory networks are commonly limited to gene entities. To integrate networks with post transcriptional regulatory data, researchers are therefore forced to manually resort to specific third party databases. In this context, we introduce ReNE, a Cytoscape 3.x plugin designed to automatically enrich a standard gene-based regulatory network with more detailed transcriptional, post transcriptional, and translational data, resulting in an enhanced network that more precisely models the actual biological regulatory mechanisms. ReNE can automatically import a network layout from the Reactome or KEGG repositories, or work with custom pathways described using a standard OWL/XML data format that the Cytoscape import procedure accepts. Moreover, ReNE allows researchers to merge multiple pathways coming from different sources. The merged network structure is normalized to guarantee a consistent and uniform description of the network nodes and edges and to enrich all integrated data with additional annotations retrieved from genome-wide databases like NCBI, thus producing a pathway fully manageable through the Cytoscape environment. The normalized network is then analyzed to include missing transcription factors, miRNAs, and proteins. The resulting enhanced network is still a fully functional Cytoscape network where each regulatory element (transcription factor, miRNA, gene, protein) and regulatory mechanism (up-regulation/down-regulation) is clearly visually identifiable, thus enabling a better visual understanding of its role and the effect in the network behavior. The enhanced network produced by ReNE is exportable in multiple formats for further analysis via third party applications. ReNE can be freely installed from the Cytoscape App Store (http://apps.cytoscape.org/apps/rene) and the full source code is freely available for download through a SVN repository accessible at http://www.sysbio.polito.it/tools_svn/BioInformatics/Rene/releases/. ReNE enhances a network by only integrating data from public repositories, without any inference or prediction. The reliability of the introduced interactions only depends on the reliability of the source data, which is out of control of ReNe developers.