THE IMPACT OF COVID-19 ON THE TOURISM SECTOR IN BOSNIA AND HERZEGOVINA

In this study, we examine the degree of persistence in tourism in Bosnia and Herzegovina and the impact that the COVID-19 pandemic has had on it. The series investigated are foreign arrivals and overnight stays for the time period from January 2008 to December 2021. The methodology used is based on fractional integration. The results indicate that the impact of COVID-19 has been strong on the series, removing the significance of the time trend, increasing the level of persistence and reducing significantly the seasonality factor in both arrivals and overnight stay series

Exogenous shocks and time-varying price persistence in the EU27

JEL Classification: C22; E31This paper analyses monthly price persistence in the EU27 countries over the period 2010–2022 using a fractional integration framework, where the measure of persistence is the fractional differencing parameter d. In addition to full sample estimates, subsample and recursive ones are obtained to examine time variation. On the whole, the results provide clear evidence that both the exogenous shocks considered (namely, the COVID-19 pandemic and the Russia-Ukraine war) have generally increased price persistence in the EU27 (despite their heterogeneity), although the recursive estimates suggest that their impact might have peaked and might now be decreasing. Therefore, any policies adopted to counteract those shocks should be gradually phased out. The exceptions are the Southern European countries, where price persistence appears to have decreased, though in Italy the recursive analysis indicates that it is now rising sharply.Ministerio de Ciencia e Innovación [PID2020-113691RB-I00] funded by MCIN/AEI/10.13039/501100011033; internal Project from the Universidad Francisco de Vitoria

Persistence in the cryptocurrency market: the impact of the Covid-19 pandemic and of the Russia-Ukraine war

This paper uses fractional integration methods to analyse persistence in the five cryptocurrencies with the highest degree of market capitalization (Bitcoin, Ethereum, Tether, BNB and USD Coin), and also the possible impact of both the Covid-19 pandemic and the Russia-Ukraine war. The findings suggest mean reversion in the case of the USD Coin, an explosive pattern in the case of BNB, and anti-persistence in the case of Tether. The unit root null hypothesis cannot be rejected in the case of Bitcoin, Ethereum and USD Coin, whilst it is rejected in favour of d > 1 in the case of BNB (where d is the fractional differencing parameter measuring persistence). Finally, there is not much evidence that either the Covid-19 pandemic or the Russia-Ukraine conflict have significantly affected persistence in the cryptocurrency market

Improved end-member characterisation of modern organic matter pools in the Ohrid Basin (Albania, Macedonia) and evaluation of new palaeoenvironmental proxies

We present elemental, lipid biomarker and, in the supplement, compound-specific isotope (δ13C, δ2H) data for soils and leaf litter collected in the catchment of Lake Ohrid (Albania, Macedonia), as well as macrophytes, particulate organic matter and sediments from the lake itself. Lake Ohrid provides an outstanding archive of continental environmen- tal change of at least 1.2 million years and the purpose of our study is to ground truth organic geochemical proxies that we developed in order to study past changes in the terres- trial biome. We show that soils dominate the lipid signal of the lake sediments rather than the vegetation or aquatic biomass. There is a strong imprint of suberin monomers on the composition of total lipid extracts and chain-length distri- butions of n-alkanoic acids, n-alcohols, ω-hydroxy acids and α, ω-dicarboxylic acids. Our end-member survey identifies that ratios of mid-chain length suberin-derived to long-chain length cuticular-derived alkyl compounds as well as their av- erage chain length distributions can be used as new molecular proxies of organic matter sources to the lake. We tested these for the 8.2 ka event, a pronounced and widespread Holocene climate fluctuation. In SE Europe climate became drier and cooler in response to the event, as is clearly recognisable in the carbonate and organic carbon records of Lake Ohrid sed- iments. Our new proxies indicate biome modification in re- sponse to hydrological changes, identifying two phases of in- creased soil organic matter (OM) supply, first from soils with moderately degraded OM and then from more degraded soils. Our study demonstrates that geochemical fingerprinting of terrestrial OM should focus on the main lipid sources, rather than the living biomass. Both can exhibit climate-controlled variability, but are generally not identical

Neurogenic and pericytic plasticity of conditionally immortalized cells derived from renal erythropoietin‐producing cells

In adult mammals, the kidney is the main source of circulating erythropoietin (Epo), the master regulator of erythropoiesis. In vivo data in mice demonstrated multiple subtypes of interstitial renal Epo-producing (REP) cells. To analyze the differentiation plasticity of fibroblastoid REP cells, we used a transgenic REP cell reporter mouse model to generate conditionally immortalized REP-derived (REPD) cell lines. Under nonpermissive conditions, REPD cells ceased from proliferation and acquired a stem cell-like state, with strongly enhanced hypoxia-inducible factor 2 (HIF-2α), stem cell antigen 1 (SCA-1), and CD133 expression, but also enhanced alpha-smooth muscle actin (αSMA) expression, indicating myofibroblastic signaling. These cells maintained the “on-off” nature of Epo expression observed in REP cells in vivo, whereas other HIF target genes showed a more permanent regulation. Like REP cells in vivo, REPD cells cultured in vitro generated long tunneling nanotubes (TNTs) that aligned with endothelial vascular structures, were densely packed with mitochondria and became more numerous under hypoxic conditions. Although inhibition of mitochondrial oxygen consumption blunted HIF signaling, removal of the TNTs did not affect or even enhance the expression of HIF target genes. Apart from pericytes, REPD cells readily differentiated into neuroglia but not adipogenic, chondrogenic, or osteogenic lineages, consistent with a neuronal origin of at least a subpopulation of REP cells. In summary, these results suggest an unprecedented combination of differentiation features of this unique cell type

Efficacy of Benralizumab in severe asthma in real life and focus on nasal polyposis

Introduction: Severe asthma occurs in 5–10% of asthmatic patients, with nasal polyposis as one of the most frequent comorbidity. Benralizumab was recently marketed, thus we could analyse its effects in real-life in severe asthma, and compare the effects of the drug in patients with and without polyposis. Methods: Patients with severe asthma, receiving Benralizumab were enrolled in Italian asthma centres. The efficacy criteria for asthma (exacerbation rate, oral corticosteroid intake, hospitalizations, pulmonary function, exhaled nitric oxide) were evaluated at baseline and after 24 weeks of treatment. Patients were then sub-analysed according to the presence/absence of nasal polyposis. Results: Fifty-nine patients with severe uncontrolled asthma (21 males, age range 32–78) and treated with benralizumab for at least 24 weeks has been evaluated, showing significant improvements in asthma-related outcomes, except for pulmonary function and exhaled nitric oxide. This included a reduction in the sino-nasal outcome-22 score versus baseline of 13.7 points (p = .0037) in the 34 patients with nasal polyposis. Anosmia disappeared in 31% patients (p = .0034). When comparing the groups with and without nasal polyposis, a similar reduction of exacerbations was seen, with a greater reduction of the steroid dependence in patients with polyposis (−72% vs −53%; p < .0001), whereas lung function was significantly more improved (12% vs 34%, p = .0064) without polyposis patients. Conclusions: Benralizumab, after 6 months of treatment, confirmed its efficacy in severe asthma, and also in nasal polyposis, which is the most frequent comorbidity. The efficacy of Benralizumab in reducing steroid dependence was even higher in patients with polyposis

Lymphangioleiomyomatosis, multifocal micronodular pneumocyte hyperplasia, and sarcoidosis : More pathological findings in the same chest CT, or a single pathological pathway?

Background: Autoimmune hepatitis/primary biliary cirrhosis overlap syndrome, lymphangioleiomyomatosis/tuberous sclerosis complex (LAM-TSC), and sarcoidosis are three rare diseases. Here we present, to the best of our knowledge, the first description of a patient with the coexistence of these three diseases. Case presentation: A 47-year-old woman affected by LAM-TSC and primary biliary cirrosis/autoimmune hepatitis overlap syndrome. During her follow up a high resolution chest CT scan (HRTC) confirmed the presence of both multiple cysts and micronodular opacities consistent with multifocal micronodular pneumocytes hyperlasia (MMPH), and revealed multiple hilar-mediastinal symmetrical lymphadenopathies suggestive of sarcoidosis. Simultaneously, subcutaneous nodules appeared on her forearm bilaterally. Cutaneous biopsy showed granulomatous dermatitis with sarcoid-like granulomas. A diagnosis of stage I pulmonary sarcoidosis was made. No treatment for sarcoidosis was initiated since the patient had neither systemic involvement, nor respiratory impairment. Conclusions: The presence of more than one rare disease should challenge the concept of a potential common underlying mechanism, since the a priori probability of the concomitant presence of different conditions with different pathogenic mechanisms - especially if rare diseases - is low. We speculate that the dysregulation of the pathway involving mTOR and MAPK and their interaction might play a role in the pathogenesis of other diseases, including sarcoidosis

Occurrence and transmission potential of asymptomatic and presymptomatic SARS-CoV-2 infections : update of a living systematic review and meta-analysis

Funding: This study was funded by the Swiss National Science Foundation http://www.snf.ch/en (NL: 320030_176233); the European Union Horizon 2020 research and innovation programme https://ec.europa.eu/programmes/horizon2020/en (NL: 101003688); the Swiss government excellence scholarship https://www.sbfi.admin.ch/sbfi/en/home/education/scholarships-and-grants/swiss-government-excellence-scholarships.html (DBG: 2019.0774) and the Swiss School of Public Health Global P3HS stipend https://ssphplus.ch/en/ (DBG).Background : Debate about the level of asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection continues. The amount of evidence is increasing and study designs have changed over time. We updated a living systematic review to address 3 questions: (1) Among people who become infected with SARS-CoV-2, what proportion does not experience symptoms at all during their infection? (2) What is the infectiousness of asymptomatic and presymptomatic, compared with symptomatic, SARS-CoV-2 infection? (3) What proportion of SARS-CoV-2 transmission in a population is accounted for by people who are asymptomatic or presymptomatic? Methods and findings : The protocol was first published on 1 April 2020 and last updated on 18 June 2021. We searched PubMed, Embase, bioRxiv, and medRxiv, aggregated in a database of SARS-CoV-2 literature, most recently on 6 July 2021. Studies of people with PCR-diagnosed SARS-CoV-2, which documented symptom status at the beginning and end of follow-up, or mathematical modelling studies were included. Studies restricted to people already diagnosed, of single individuals or families, or without sufficient follow-up were excluded. One reviewer extracted data and a second verified the extraction, with disagreement resolved by discussion or a third reviewer. Risk of bias in empirical studies was assessed with a bespoke checklist and modelling studies with a published checklist. All data syntheses were done using random effects models. Review question (1): We included 130 studies. Heterogeneity was high so we did not estimate a mean proportion of asymptomatic infections overall (interquartile range (IQR) 14% to 50%, prediction interval 2% to 90%), or in 84 studies based on screening of defined populations (IQR 20% to 65%, prediction interval 4% to 94%). In 46 studies based on contact or outbreak investigations, the summary proportion asymptomatic was 19% (95% confidence interval (CI) 15% to 25%, prediction interval 2% to 70%). (2) The secondary attack rate in contacts of people with asymptomatic infection compared with symptomatic infection was 0.32 (95% CI 0.16 to 0.64, prediction interval 0.11 to 0.95, 8 studies). (3) In 13 modelling studies fit to data, the proportion of all SARS-CoV-2 transmission from presymptomatic individuals was higher than from asymptomatic individuals. Limitations of the evidence include high heterogeneity and high risks of selection and information bias in studies that were not designed to measure persistently asymptomatic infection, and limited information about variants of concern or in people who have been vaccinated. Conclusions : Based on studies published up to July 2021, most SARS-CoV-2 infections were not persistently asymptomatic, and asymptomatic infections were less infectious than symptomatic infections. Summary estimates from meta-analysis may be misleading when variability between studies is extreme and prediction intervals should be presented. Future studies should determine the asymptomatic proportion of SARS-CoV-2 infections caused by variants of concern and in people with immunity following vaccination or previous infection. Without prospective longitudinal studies with methods that minimise selection and measurement biases, further updates with the study types included in this living systematic review are unlikely to be able to provide a reliable summary estimate of the proportion of asymptomatic infections caused by SARS-CoV-2. Review protocol : Open Science Framework (https://osf.io/9ewys/)Publisher PDFPeer reviewe

Women with TSC : Relationship between Clinical, Lung Function and Radiological Features in a Genotyped Population Investigated for Lymphangioleiomyomatosis

The advent of pharmacological therapies for lymphangioleiomyomatosis (LAM) has made early diagnosis important in women with tuberous sclerosis complex (TSC), although the lifelong cumulative radiation exposure caused by chest computer tomography (CT) should not be underestimated. We retrospectively investigated, in a cohort of TSC outpatients of San Paolo Hospital (Milan, Italy) 1) the role of pulmonary function tests (PFTs) for LAM diagnosis, 2) the association between LAM and other features of TSC (e.g. demography, extrapulmonary manifestations, genetic mutations, etc.), and 3) the characteristics of patients with multifocal micronodular pneumocyte hyperplasia (MMPH). Eighty-six women underwent chest CT scan; pulmonary involvement was found in 66 patients (77%; 49% LAM with or without MMPH, and 28% MMPH alone). LAM patients were older, with a higher rate of pneumothorax, presented more frequently with renal and hepatic angiomyolipomas, and tended to have a TSC2 mutation profile. PFTs, assessed in 64% of women unaffected by cognitive impairments, revealed a lower lung diffusion capacity in LAM patients. In multivariate analysis, age, but not PFTs, resulted independently associated with LAM diagnosis. Patients with MMPH alone did not show specific clinical, functional or genetic features. A mild respiratory impairment was most common in LAM-TSC patients: In conclusions, PFTs, even if indicated to assess impairment in lung function, are feasible in a limited number of patients, and are not significantly useful for LAM diagnosis in women with TSC

Continuous population-level monitoring of SARS-CoV-2 seroprevalence in a large European metropolitan region

Effective public health measures against SARS-CoV-2 require granular knowledge of population-level immune responses. We developed a Tripartite Automated Blood Immunoassay (TRABI) to assess the IgG response against three SARS-CoV-2 proteins. We used TRABI for continuous seromonitoring of hospital patients and blood donors (n = 72'250) in the canton of Zurich from December 2019 to December 2020 (pre-vaccine period). We found that antibodies waned with a half-life of 75 days, whereas the cumulative incidence rose from 2.3% in June 2020 to 12.2% in mid-December 2020. A follow-up health survey indicated that about 10% of patients infected with wildtype SARS-CoV-2 sustained some symptoms at least twelve months post COVID-19. Crucially, we found no evidence of a difference in long-term complications between those whose infection was symptomatic and those with asymptomatic acute infection. The cohort of asymptomatic SARS-CoV-2-infected subjects represents a resource for the study of chronic and possibly unexpected sequelae