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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.

Long-term pulmonary sequelae in COVID-19 patients are currently under investigation worldwide. Potential relationships between blood sampling and functional and radiological findings are crucial to guide the follow-up. In this study, we collected and evaluated clinical status, namely symptoms and patients’ reported outcome, pulmonary function tests (PFT), laboratory tests, and radiological findings at 3- and 12-months post-discharge in patients admitted between 25 February and 2 May 2020, and who survived severe COVID-19 pneumonia. A history of chronic pulmonary disease or COVID-19-unrelated complications were used as exclusion criteria. Unenhanced CTs were analyzed quantitatively (compromising lung volume %) and qualitatively, with main patterns of: ground-glass opacity (GGO), consolidation, and reticular configuration. Patients were subsequently divided into groups based on their radiological trends and according to the evolution in the percentage of compromised lung volume. At 12 months post-discharge, seventy-one patients showed significantly improved laboratory tests and PFT. Among them, 63 patients also underwent CT examination: all patients with negative CT findings at three months (n = 14) had negative CT also at 12 months; among the 49/63 patients presenting CT alterations at three months, 1/49 (2%) normalized, 40/49 (82%) improved, 7/49 (14%) remained stably abnormal, and 1/49 (2%) worsened. D-dimer values were low in patients with normal CT and higher in cases with improved or stably abnormal CT (median values 213 vs. 329 vs. 1000 ng/mL, respectively). The overall compromised lung volume was reduced compared with three months post-discharge (12.3 vs. 14.4%, p < 0.001). In stably abnormal CT, the main pulmonary pattern changed, showing a reduction in GGO and an increase in reticular configuration. To summarize, PFT are normal in most COVID-19 survivors 12 months post-discharge, but CT structural abnormalities persist (although sensibly improved over time) and are associated with higher D-dimer values.

States in the context of foreign policy apply specific strategies that relate with strengthening their international position, especially in relation to the promotion of attributes and values that make changing the perceptions of citizens of other states, and consequently of decision makers. Small states find it difficult to impose on the large international system knowing that their power and potential is little measurable.

Purpose: The ability to generate natural killer (NK) cells from induced pluripotent stem cells (iPSCs) has given rise to new possibilities for the large-scale production of homogeneous immunotherapeutic cellular products and opened new avenues towards the creation of "off-the-shelf" cancer immunotherapies. However, the differentiation of NK cells from iPSCs remains poorly understood, particularly regarding the ontogenic landscape of iPSC-derived NK (iNK) cells produced in vitro and the influence that the differentiation strategy employed may have on the iNK profile. Methods: To investigate this question, we conducted a comparative analysis of two sets of iNK cells generated from the same iPSC line using two different protocols: (i) a short-term, clinically compatible feeder-free protocol corresponding to primitive hematopoiesis, and (ii) a lymphoid-based protocol representing the definitive hematopoietic step. Results and discussion: Our work demonstrated that both protocols are capable of producing functional iNK cells. However, the two sets of resulting iNKs exhibited distinct phenotypes and transcriptomic profiles. The lymphoid-based differentiation approach generated iNKs with a more mature and activated profile, which demonstrated higher cytotoxicity against cancer cell lines compared to iNK cells produced under short-term feeder-free conditions suggesting that the differentiation strategy must be considered when designing iNK cell-based adoptive immunotherapies. [ABSTRACT FROM AUTHOR]

This research paper analyzes how the pandemic caused by the coronavirus has affected eight MENA and three OIC stock market indices using advanced methodologies based on fractional integration. With this methodology we try to measure the persistence of the financial data in order to understand the long-term market dynamics of these two regions and to identify whether the COVID-19 shock has caused structural changes in the time series. Moreover, we want to identify if the shocks in the series have had permanent or transitory effects. The time period examined starts from pre-pandemic times at 2003, and first goes to the end of 2019; then, we also consider the COVID-19 pandemic (with data ending at December 2021) and then extend the analysis onwards to include the war between Russia and Ukraine (data ending at February 2023). The results indicate that there have not been significant long-lasting impacts from the COVID-19 pandemic or the Russia-Ukraine war on the degree of persistence in the series when using monthly data; however, as far as daily and weekly data are concerned the shocks have had some effect on the degree of persistence with daily data in the cases of Egypt, Indonesia, Malaysia, Turkey, and with weekly data for Bahrain, Egypt, Kuwait, Malaysia, Morocco and Turkey. [ABSTRACT FROM AUTHOR]

REarranged during Transfection (RET) oncogenic rearrangements can occur in 1–2% of lung adenocarcinomas. While RET-driven NSCLC models have been developed using various approaches, no model based on patient-derived induced pluripotent stem cells (iPSCs) has yet been described. Patient-derived iPSCs hold great promise for disease modeling and drug screening. However, generating iPSCs with specific oncogenic drivers, like RET rearrangements, presents challenges due to reprogramming efficiency and genotypic variability within tumors. To address this issue, we aimed to generate lung progenitor cells (LPCs) from patient-derived iPSCs carrying the mutation RETC634Y, commonly associated with medullary thyroid carcinoma. Additionally, we established a RETC634Y knock-in iPSC model to validate the effect of this oncogenic mutation during LPC differentiation. We successfully generated LPCs from RETC634Y iPSCs using a 16-day protocol and detected an overexpression of cancer-associated markers as compared to control iPSCs. Transcriptomic analysis revealed a distinct signature of NSCLC tumor repression, suggesting a lung multilineage lung dedifferentiation, along with an upregulated signature associated with RETC634Y mutation, potentially linked to poor NSCLC prognosis. These findings were validated using the RETC634Y knock-in iPSC model, highlighting key cancerous targets such as PROM2 and C1QTNF6, known to be associated with poor prognostic outcomes. Furthermore, the LPCs derived from RETC634Y iPSCs exhibited a positive response to the RET inhibitor pralsetinib, evidenced by the downregulation of the cancer markers. This study provides a novel patient-derived off-the-shelf iPSC model of RET-driven NSCLC, paving the way for exploring the molecular mechanisms involved in RET-driven NSCLC to study disease progression and to uncover potential therapeutic targets.

The process of recognition of Kosovo has continuously declined since the Declaration of Independence until 2021, the period covered in this paper. This process is characterized by external structural obstacles, as well as internal non-structural ones. Applying the content analysis method and semi-structured interviews, the paper emphasized that the main structural obstacle was the inability to accept the Ahtisaari Plan from the UN as a compromise choice. On the other hand, the non-recognition of the state of Kosovo by Serbia (supported by Russia) resulted in the division of the states into two large groups: “pro” and “contra” recognition. Meanwhile, due to these extreme divisions, a third group of states sees the recognition of Kosovo as an opportunity to solve the previous obstacles. Thus, Serbia has established clear schemes to hinder the development of the process, first by sending the case of Kosovo to the ICJ and later by presenting the Kosovo-Serbia negotiation as status negotiations. Meanwhile, the internal political instability in Kosovo and the wrong political approach towards potentially recognizing states are evident as non-structural obstacles in achieving new recognition.

The classical natural history of chronic myeloid leukemia (CML) has been drastically modified by the introduction of tyrosine kinase inhibitor (TKI) therapies. TKI discontinuation is currently possible in patients in deep molecular responses, using strict recommendations of molecular follow-up due to risk of molecular relapse, especially during the first 6 months. We report here the case of a patient who voluntarily interrupted her TKI therapy. She remained in deep molecular remission (MR4) for 18 months followed by detection of a molecular relapse at +20 months. Despite this relapse, she declined therapy until the occurrence of the hematological relapse (+ 4 years and 10 months). Retrospective sequential transcriptome experiments and a single-cell transcriptome RNA-seq analysis were performed. They revealed a molecular network focusing on several genes involved in both activation and inhibition of NK-T cell activity. Interestingly, the single-cell transcriptome analysis showed the presence of cells expressing NKG7, a gene involved in granule exocytosis and highly involved in anti-tumor immunity. Single cells expressing as granzyme H, cathepsin-W, and granulysin were also identified. The study of this case suggests that CML was controlled for a long period of time, potentially via an immune surveillance phenomenon. The role of NKG7 expression in the occurrence of treatment-free remissions (TFR) should be evaluated in future studies.

Summary: 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.

Background: Vaccinations are successful, cost-effective tools to prevent the spread of certain infectious diseases. Many colleges conduct vaccination campaigns on their campuses for various vaccine-preventable diseases, including measles, mumps, influenza, HPV, and most recently, for SARS-CoV-2, the virus responsible for COVID-19. Implementing these campaigns requires substantial effort and understanding their effectiveness is an important factor in justifying these programs. Aim: This scoping review aims to identify, review, and summarize existing evaluation methods for vaccination campaigns on college campuses in order to provide evaluation guidance for institutions planning future vaccination campaigns. Methods: Publications that focused on vaccination campaigns on college campuses for students and/or faculty and staff and described their evaluation methods were included in our analysis. A systematic search of the literature identified 2,101 articles. After duplicates were removed, titles and abstracts were screened, and references searched, 43 articles were identified for full-text review. Sixteen articles provided evaluation information and were systematically reviewed. Results: Interventions targeted a variety of vaccine-preventable diseases, with the majority either aiming to increase HPV vaccine uptake or vaccinate against meningococcal serogroups. Most studies reported on campaigns that included both educational activities and provided vaccinations. Evaluation methods varied widely. Some studies measured vaccine-related knowledge and attitudes. Vaccine uptake was most commonly measured as a simple count of doses administered. Conclusions: College campus vaccination campaigns are evaluated in multiple ways, with little consistency in how the effectiveness of campaigns are measured. There is a need to develop clear evaluation methods for college vaccination programs, especially how to calculate vaccination rates associated with these efforts.

Die Frage, inwieweit Datenmanagement jenseits von entweder generischen oder fachspezifischen Perspektiven denkbar ist, stand im Mittelpunkt eines Workshops im Rahmen der FORGE 2021. Im Workshop wurde das Konzept der „Data Communities“ (Cooper und Springer 2019) vorgestellt, seine Potenziale mit Blick auf die Sozial- und Geisteswissenschaften diskutiert und anschließend eruiert, welche strategischen wie operativen Kriterien sich daraus für forschungsadäquat unterstützende Datenmanagement-Services ableiten lassen. Der Beitrag fasst die wichtigsten Erkenntnisse aus dem Workshop zusammen und diskutiert, wie das bestehende Konzept um spezifisch sozial- und geisteswissenschaftliche Aspekte erweitert werden könnte.

Valve disease in the presence of porcelain aorta and severe peripheral artery disease challenge physicians in choosing the appropriate therapy. We used a total transcatheter approach, simultaneously implanting a dedicated mitral and aortic valve prosthesis treating a patient with mitral and aortic valve disease at an extremely high surgical risk. (Level of Difficulty: Advanced.)

Abstract The use of mesenchymal stem cells (MSC) derived from several sources has been suggested as a major anti‐inflammation strategy during the recent outbreak of coronavirus‐19 (COVID‐19). As the virus enters the target cells through the receptor ACE2, it is important to determine if the MSC population transfused to patients could also be a target for the virus entry. We report here that ACE2 is highly expressed in adult bone marrow, adipose tissue, or umbilical cord‐derived MSC. On the other hand, placenta‐derived MSC express low levels of ACE2 but only in early passages of cultures. MSC derived from human embryonic stem cell or human induced pluripotent stem cells express also very low levels of ACE2. The transcriptome analysis of the MSCs with lowest expression of ACE2 in fetal‐like MSCs is found to be associated in particularly with an anti‐inflammatory signature. These results are of major interest for designing future clinical MSC‐based stem cell therapies for severe COVID‐19 infections.

Purpose – This study deals with the COVID-19’s effects on the travel sector in ASEAN countries and applies fractional integration methods. Methodology/Design/Approach – The persistence and seasonality of foreign tourist visitors in ASEAN members is investigated using monthly data at different time periods. Findings – The results demonstrate that the series’ nature has undergone significant changes as a result of the present epidemic, moving from mean reversion in the period before Covid, to its absence once the data of the pandemic are incorporated in the series. In fact, using the whole dataset, the hypothesis of a unit root cannot be rejected and seasonality becomes almost irrelevant in all series examined. On this basis, the results suggest for more active involvement of certain governments in recovering the tourism industry with the intention of reaching the original trend. Originality of the research – To our knowledge ne previous study was conducted to analyze the COVID-19’s effects on the travel sector in ASEAN countries through fractional integration methods. [ABSTRACT FROM AUTHOR]

Abstract Background Outbreaks of infectious diseases generate outbreaks of scientific evidence. In 2016 epidemics of Zika virus emerged, and in 2020, a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a pandemic of coronavirus disease 2019 (COVID-19). We compared patterns of scientific publications for the two infections to analyse the evolution of the evidence. Methods We annotated publications on Zika virus and SARS-CoV-2 that we collected using living evidence databases according to study design. We used descriptive statistics to categorise and compare study designs over time. Results We found 2286 publications about Zika virus in 2016 and 21,990 about SARS-CoV-2 up to 24 May 2020, of which we analysed a random sample of 5294 (24%). For both infections, there were more epidemiological than laboratory science studies. Amongst epidemiological studies for both infections, case reports, case series and cross-sectional studies emerged first, cohort and case-control studies were published later. Trials were the last to emerge. The number of preprints was much higher for SARS-CoV-2 than for Zika virus. Conclusions Similarities in the overall pattern of publications might be generalizable, whereas differences are compatible with differences in the characteristics of a disease. Understanding how evidence accumulates during disease outbreaks helps us understand which types of public health questions we can answer and when.

Abstract Background Gender-related factors might affect vulnerability to Covid-19. The aim of this study was to describe the role of gender on clinical features and 28-day mortality in Covid-19 patients. Methods Observational study of Covid-19 patients hospitalized in Bergamo, Italy, during the first three weeks of the outbreak. Medical records, clinical, radiological and laboratory findings upon admission and treatment have been collected. Primary outcome was 28-day mortality since hospitalization. Results 431 consecutive adult patients were admitted. Female patients were 119 (27.6%) with a mean age of 67.0 ± 14.5 years (vs 67.8 ± 12.5 for males, p = 0.54). Previous history of myocardial infarction, vasculopathy and former smoking habits were more common for males. At the time of admission PaO2/FiO2 was similar between men and women (228 [IQR, 134–273] vs 238 mmHg [150–281], p = 0.28). Continuous Positive Airway Pressure (CPAP) assistance was needed in the first 24 h more frequently in male patients (25.7% vs 13.0%; p = 0.006). Overall 28-day mortality was 26.1% in women and 38.1% in men (p = 0.018). Gender did not result an independent predictor of death once the parameters related to disease severity at presentation were included in the multivariable analysis (p = 0.898). Accordingly, the Kaplan–Meier survival analysis in female and male patients requiring CPAP or non-invasive ventilation in the first 24 h did not find a significant difference (p = 0.687). Conclusion Hospitalized women are less likely to die from Covid-19; however, once severe disease occurs, the risk of dying is similar to men. Further studies are needed to better investigate the role of gender in clinical course and outcome of Covid-19.