Epidemiology of Porcine Circovirus Type 2 Circulating in Wild Boars of Portugal during the 2018–2020 Hunting Seasons Suggests the Emergence of Genotype 2d

Porcine circovirus type 2 (PCV-2) is associated with several syndromes affecting swine, also known as porcine-circovirus-associated diseases, of which post-weaning multi-systemic wasting syndrome stands out due to its high economic impact on swine production. Recent data suggest the increasing circulation of the PCV-2d genotype in several countries worldwide. To provide updated data on PCV-2 genotypes currently circulating in swine in Portugal, we screened wild boar stools collected from several districts across Portugal, during the 2018–2020 hunting seasons, for PCV-2 and genetically characterized detected strains. From a total of 76 stool samples of wild boar tested by PCR for the partial PCV-2 ORF2 gene, two sequences were obtained (2/76; 2.6%, 95% confidence interval: 0.032–9.18). Bidirectional sequencing showed that the sequences were 100% identical and both of the PCV-2d genotype, showing for the first time the presence of this genotype in Portugal. Monitoring wild PCV-2 reservoirs is important for both veterinary public health and economic reasons, since PCV-2 infection has a strong economic impact on the swine industry. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Funding text 1: Funding: Sérgio Santos-Silva thanks Fundação para a Ciência e a Tecnologia (FCT) for the financial support of his PhD work under the 2021 scholarship. 09461.BD contract through the Maria de Sousa-2021 program. Part of this research was funded by the project EcoARUn: POCI-01-0145-FEDER-030310 funded by FEDER, through COMPETE2020-Programa Operacional Competitividade e Internacionalização (POCI), and by national funds (OE), through Fundação para a Ciência e a Tecnologia/Ministério da Ciência e Tecnologia e Ensino Superior. R. T. Torres is funded by national funds (OE) and through FCT, in the scope of the framework contract foreseen in the numbers 4, 5 and 6 of the article 23, of the Decree-Law 57/2016, of August 29, changed by Law 57/2017, of July 19. Thanks are due to FCT/MCTES for the financial support to CESAM (UIDP/50017/2020 + UIDB/50017/2020), through national funds (FCT). This work is financed by national funds through FCT—Fundação para a Ciência e a Tecnologia, I.P., under the projects UIDB/04750/2020 and LA/P/0064/2020.; Funding text 2: S?rgio Santos-Silva thanks Funda??o para a Ci?ncia e a Tecnologia (FCT) for the financial support of his PhD work under the 2021 scholarship. 09461.BD contract through the Maria de Sousa-2021 program. Part of this research was funded by the project EcoARUn: POCI-01-0145-FEDER-030310 funded by FEDER, through COMPETE2020-Programa Operacional Competitividade e Internacionaliza??o (POCI), and by national funds (OE), through Funda??o para a Ci?ncia e a Tecnologia/Minist?rio da Ci?ncia e Tecnologia e Ensino Superior. R. T. Torres is funded by national funds (OE) and through FCT, in the scope of the framework contract foreseen in the numbers 4, 5 and 6 of the article 23, of the Decree-Law 57/2016, of August 29, changed by Law 57/2017, of July 19. Thanks are due to FCT/MCTES for the financial support to CESAM (UIDP/50017/2020 + UIDB/50017/2020), through national funds (FCT). This work is financed by national funds through FCT?Funda??o para a Ci?ncia e a Tecnologia, I.P., under the projects UIDB/04750/2020 and LA/P/0064/2020

A randomised controlled trial and cost-consequence analysis of traditional and digital foot orthoses supply chains in a National Health Service setting : application to feet at risk of diabetic plantar ulceration

Background: Diabetic foot ulceration is a considerable cost to the NHS and foot orthotic provision is a core strategy for the management of the people with diabetes and a moderate to high risk of foot ulceration. The traditional process to produce a custom-made foot orthotic device is to use manual casting of foot shape and physical moulding of orthoses materials. Parts of this process can be undertaken using digital tools rather than manual processes with potential advantages. The aim of this trial was to provide the first comparison of a traditional orthoses supply chain to a digital supply chain over a 6 month period. The trial used plantar pressure, health status, and health service time and cost data to compare the two supply chains. Methods: 57 participants with diabetes were randomly allocated to each supply chain. Plantar pressure data and health status (EQ5D, ICECAP) was assessed at point of supply and at sixmonths. The costs for orthoses and clinical services accessed by participants were assessed over the 6 months of the trial. Primary outcomes were: reduction in peak plantar pressure at the site of highest pressure, assessed for non-inferiority to current care. Secondary outcomes were: reduction in plantar pressure at foot regions identified as at risk (>200kPa), costconsequence analysis (supply chain, clinician time, service use) and health status. Results: At point of supply pressure reduction for the digital supply chain was non-inferior to a predefined margin and superior (p<0.1) to the traditional supply chain, but both supply chains were inferior to the margin after six months. Custom-made orthoses significantly reduced pressure for at risk regions compared to a flat control (traditional -13.85%, digital -20.52%). The digital supply chain was more expensive (+£13.17) and required more clinician time (+35minutes). There were no significant differences in health status or service use between supply chains. Conclusions: Custom made foot orthoses reduce pressure as expected. Given some assumptions about the cost models we used, the supply chain process adopted to produce the orthoses seems to have marginal impact on overall costs and health status. Trial Registration: retrospectively registered on ISRCTN registry (ISRCTN10978940, 04/11/2015). Key Words: Foot Orthotic, Biomechanics, Diabetes, Plantar Pressure, Cost, Health Economics, Supply Chai

Clinical use of HIV integrase inhibitors : a systematic review and meta-analysis

Background: Optimal regimen choice of antiretroviral therapy is essential to achieve long-term clinical success. Integrase inhibitors have swiftly been adopted as part of current antiretroviral regimens. The purpose of this study was to review the evidence for integrase inhibitor use in clinical settings. Methods: MEDLINE and Web-of-Science were screened from April 2006 until November 2012, as were hand-searched scientific meeting proceedings. Multiple reviewers independently screened 1323 citations in duplicate to identify randomized controlled trials, nonrandomized controlled trials and cohort studies on integrase inhibitor use in clinical practice. Independent, duplicate data extraction and quality assessment were conducted. Results: 48 unique studies were included on the use of integrase inhibitors in antiretroviral therapy-naive patients and treatment-experienced patients with either virological failure or switching to integrase inhibitors while virologically suppressed. On the selected studies with comparable outcome measures and indication (n = 16), a meta-analysis was performed based on modified intention-to-treat (mITT), on-treatment (OT) and as-treated (AT) virological outcome data. In therapy-naive patients, favorable odds ratios (OR) for integrase inhibitor-based regimens were observed, (mITT OR 0.71, 95% CI 0.59-0.86). However, integrase inhibitors combined with protease inhibitors only did not result in a significant better virological outcome. Evidence further supported integrase inhibitor use following virological failure (mITT OR 0.27; 95% CI 0.11-0.66), but switching to integrase inhibitors from a high genetic barrier drug during successful treatment was not supported (mITT OR 1.43; 95% CI 0.89-2.31). Integrase inhibitor-based regimens result in similar immunological responses compared to other regimens. A low genetic barrier to drug-resistance development was observed for raltegravir and elvitegravir, but not for dolutegravir. Conclusion: In first-line therapy, integrase inhibitors are superior to other regimens. Integrase inhibitor use after virological failure is supported as well by the meta-analysis. Careful use is however warranted when replacing a high genetic barrier drug in treatment-experienced patients switching successful treatment

Lactate signalling regulates fungal β-glucan masking and immune evasion

AJPB: This work was supported by the European Research Council (STRIFE, ERC- 2009-AdG-249793), The UK Medical Research Council (MR/M026663/1), the UK Biotechnology and Biological Research Council (BB/K017365/1), the Wellcome Trust (080088; 097377). ERB: This work was supported by the UK Biotechnology and Biological Research Council (BB/M014525/1). GMA: Supported by the CNPq-Brazil (Science without Borders fellowship 202976/2014-9). GDB: Wellcome Trust (102705). CAM: This work was supported by the UK Medical Research Council (G0400284). DMM: This work was supported by UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC/K000306/1). NARG/JW: Wellcome Trust (086827, 075470,101873) and Wellcome Trust Strategic Award in Medical Mycology and Fungal Immunology (097377). ALL: This work was supported by the MRC Centre for Medical Mycology and the University of Aberdeen (MR/N006364/1).Peer reviewedPostprin

Earnings Prediction with Deep Leaning

In the financial sector, a reliable forecast the future financial performance of a company is of great importance for investors' investment decisions. In this paper we compare long-term short-term memory (LSTM) networks to temporal convolution network (TCNs) in the prediction of future earnings per share (EPS). The experimental analysis is based on quarterly financial reporting data and daily stock market returns. For a broad sample of US firms, we find that both LSTMs outperform the naive persistent model with up to 30.0% more accurate predictions, while TCNs achieve and an improvement of 30.8%. Both types of networks are at least as accurate as analysts and exceed them by up to 12.2% (LSTM) and 13.2% (TCN).Comment: 7 pages, 4 figures, 2 tables, submitted to KI202

Survey of Zoonotic Diarrheagenic Protist and Hepatitis E Virus in Wild Boar (Sus scrofa) of Portugal

Simple Summary Enteropathogenic viruses, such as hepatitis E virus, and diarrhoeagenic protists have been frequently reported in swine and can infect a wide range of mammals, including humans. Data on their fecal shedding and circulation pathways are still lacking or incomplete. Hence, the aim of the present study was to characterize the presence of microeukaryotes and HEV in the wild boar of Portugal. Of the 144 samples tested, 2 showed the presence of Cryptosporidium scrofarum, 21 Balantioides coli, 42 Blastocystis ST5, and 4 HEV genotype 3. The present work shows that potentially zoonotic protozoa and HEV are circulating in wild boar populations in Portugal. Enteropathogenic parasites and viruses have been frequently reported in swine and can infect a wide range of mammals, including humans. Among the wide variety of parasites infecting swine, diarrhoeagenic protists are among those that cause significant morbidity. Hepatitis E virus (HEV) has also been reported both in domestic pigs and wild boar and is known to have an important public health significance. These agents share the fecal-oral transmission route, but data on their fecal shedding and circulation pathways are still lacking or incomplete. Hence, the aim of the present study was to characterize the presence of microeukaryotes and HEV in the wild boar of Portugal. Wild boar stool samples (n = 144) were obtained during the official hunting seasons (October to February) in 2018/2019, 2019/2020, and 2021/2022 and tested for Cryptosporidium spp., Balantioides coli, Giardia duodenalis, Blastocystis sp., Enterocytozoon bieneusi and HEV by molecular assays, followed by sequencing and phylogenetic analysis. We have detected Cryptosporidium scrofarum (1.4%, 95% CI: 0.2-4.9), B. coli (14.6%, 95% CI: 9.2-21.4), Blastocystis ST5 (29.2%, 95% CI: 21.9-37.2) and HEV genotype 3 (2.8%, 95% CI: 0.7-6.9; subgenotypes 3e and 3m). Co-infections were observed in thirteen animals where two were positive for both HEV and B. coli, one was positive for both C. scrofarum and Blastocystis ST5, and ten were positive for both B. coli and Blastocystis ST5. Giardia duodenalis and E. bieneusi were not detected in the surveyed wild boar population. As far as we know, this is the first report describing protist infections by Cryptosporidium spp., B. coli, and Blastocystis sp., as well as the first identification of the emerging HEV genotype 3m in wild boar of Portugal. The present work shows that potentially zoonotic protozoa and HEV are circulating in wild boar populations in Portugal. Awareness and epidemic-surveillance network implementation measures targeting wild boar are needed to prevent the spread of these pathogenic agents to humans.This research was funded by Fundacao para Ciencia e Tecnologia (FCT), grant number 2021.09461.BD