EFFICACY AND SAFETY OF DAZODALIBEP (VIB4920/HZN4920) IN SUBJECTS WITH SJÖGREN'S SYNDROME: A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PROOF OF CONCEPT STUDY

BackgroundSjögren's syndrome (SS) is a chronic, systemic autoimmune disease affecting exocrine glands, primarily the salivary and tear glands, with potentially severe manifestations in multiple organs. No approved disease-modifying therapies exist. Dazodalibep (DAZ) is a biologic antagonist of CD40L.ObjectivesThe objective of this study was to evaluate the efficacy and safety of DAZ therapy in adult SS subjects with moderate-to-high systemic disease activity (NCT04129164).MethodsWe conducted a randomized, double-blind, placebo-controlled, crossover study to evaluate DAZ therapy in adult SS subjects with moderate-to-high systemic disease activity, as defined by a EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score ≥ 5. Eligible subjects were randomized 1:1 to receive intravenous DAZ 1500 mg or placebo (PBO) Q2W x 3 doses, then Q4W x 4 additional doses. Starting on Day 169, subjects initially randomized to DAZ received PBO Q4W x 5 doses and subjects randomized to PBO received DAZ Q4W x 5 doses and were then followed for 12 weeks. The primary endpoint was the change from Baseline in ESSDAI at Day 169. Safety assessments included the incidence of adverse (AEs), serious AEs (SAEs), and AEs of special interest (AESIs).ResultsThe 74 randomized subjects all received ≥1 dose of study medication (DAZ, N=36;PBO, N=38). The baseline demographics and disease characteristics were balanced between the two groups. The change from Baseline to Day 169 in ESSDAI score (LS mean ± SE), was -6.3 ± 0.6 in DAZ-treated subjects compared to -4.1 ± 0.6 in the PBO group, a difference of -2.2 (p = 0.0167). Compared to the PBO group, the DAZ group showed positive trends in the EULAR Sjögren's Syndrome Patient Reported Index score, and Functional Assessment of Chronic Illness Therapy-Fatigue score at Day 169. A post-hoc responder analysis of subjects achieving high levels (5 and 6 points) of improvement on ESSDAI favored DAZ (61.1% and 60.0%) over PBO (35.1% and 34.3%).The reported AEs were generally mild through Day 169 and similar in frequency between treatment groups. The most frequently reported AEs occurring in ≥5% of DAZ-treated subjects and >PBO were COVID-19, diarrhea, dizziness, ligament sprain, upper respiratory tract infection, contusion, device allergy, fatigue, hypertension, and oropharyngeal pain. Two SAEs were reported in a single DAZ-treated subject: this subject was a 59-year-old female who experienced a grade 3 SAE of COVID-19 infection and later died of unknown cause 46 days after last administration of DAZ (12 days after COVID-19 diagnosis). There was a single AESI of herpes zoster in a DAZ-treated subject.ConclusionDAZ is a potential new therapy for the treatment of systemic disease activity in patients with SS. SS subjects with moderate-to-high systemic disease receiving DAZ experienced a statistically significant reduction in disease activity relative to PBO as measured by the improvement in ESSDAI score. Except for a case of severe COVID-19 infection, DAZ therapy in SS subjects appeared to be well tolerated. Larger controlled trials of DAZ therapy for SS are warranted to further explore its safety profile and confirm its clinical efficacy.Table 1.Efficacy and Safety DataPBO N=38DAZ 1500 mg N=36EfficacyΔESSDAI, LS mean (SE) †-4.1 (0.6)-6.3 (0.6)*ΔESSPRI, LS mean (SE) †-1.12 (0.29)-1.80 (0.31)ΔFACIT-Fatigue, LS mean (SE) †5.8 (1.6)8.1 (1.6)AE Summary, n (%)≥1 AE23 (60.5)28 (77.8)≥1 related AE8 (21)10 (27.8)≥1 SAE01 (2.8)≥1 related SAE00≥1 AE leading to discontinuation00≥1 AESI01 (2.8)≥1 Death01 (2.8)Efficacy endpoints as of Day 169;† Analyzed using MMRM;Comparisons vs PBO;*p<0.05;AE summaries based on AEs that occurred through Day 169;AE, adverse event;AESI, adverse event of special interest;ESSDAI, EULAR Sjögren's Syndrome Disease Activity Index;ESSPRI, EULAR Sjögren's Syndrome Patient Reported Index;FACIT-Fatigue, Functional Assessment of Chronic Illness Therapy-Fatigue;PBO, placebo;SAE, serious adverse eventFigure 1.AcknowledgementsFunded by Horizon herapeutics. Medical writing support provided by B Lujan, PhD, an employee of Horizon Therapeutics.Disclosure of InterestsE. William St. Clair Consultant of: Horizon Therapeutics, Bristol Myers Squibb, CSL Behring, Resolve Therapeutics, Sonoma Biotherapeutics. Royalties: UpToDate, Liangwei Wang Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, Ilias Alevizos Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, William Rees Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, Alan Baer Consultant of: Bristol Myers Squibb, Wan Fai Ng Consultant of: Novartis, GlaxoSmithKline, Abbvie, BMS, Sanofi, MedImmune, Janssen and UCB, Ghaith Noaiseh Consultant of: Novartis, Chiara Baldini Consultant of: GSK, and Sanofi.

The Online EFL Learning Challenges in Ukrainian Tertiary Education

COVID-19 has challenged educators not only in Ukrainian universities but throughout the whole world to keep abreast with the rapid emergence of new technologies, adapt the education system to online needs, and use blended learning as a necessity of the transformed education environment. We carried out two case studies aimed at gauging the students' perception, experience, and satisfaction level on the pandemicinduced online EFL learning via a Google Forms questionnaire in 2020-2021 a.y. and 2021-2022 a.y. at Taras Shevchenko National University of Kyiv (Ukraine). The first case conducted a 16-question online survey, and an analysis unit was the responses of 112 first-year students studying English as L2 and majoring in Computer Science and Cybernetics at the University of Kyiv under the Coronavirus lockdown reality. The second case encompassed 80 respondents and was fulfilled through the same 16-question online survey under similar study conditions. The sample groups were undergraduate students of the same age (17-18 y. o.) and the English language level (B1+) enrolled in the university with similar admissions criteria, prerequisites, and curricula. The survey's participation was voluntary and anonymous. The respondents gave feedback on three question categories: EFL online learning effectiveness, technical provision satisfaction, self-organization, and confidence level. The opinions were not fully homogeneous but the majority of Computer Science and Cybernetics undergraduates in both case studies pointed out that the online EFL course was effective. The first survey findings revealed that the first-year university learners had a predominately positive attitude towards online education, describing English lessons as well-structured and engaging. Our second investigation demonstrated that apart from staff readiness, confidence, students' Internet accessibility, and motivation, the undergraduates have indicated tiredness of online meetings, pointing out that they have a lack of live communication. The obtained study results can help in understanding EFL teachers how to continue teaching and learning during such unprecedented times and to ensure a high level of education, responding to the current students' needs and priorities for successful online classes. [ FROM AUTHOR] Copyright of Romanian Journal for Multidimensional Education / Revista Romaneasca pentru Educatie Multidimensionala is the property of Lumen Publishing House and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Controversial role of neutrophilic granulocytes in the immunopathogenesis of COVID-19: correlation with imbalance of pro-inflammatory neutrophil-associated cytokines and interferon alpha deficiency.

Neutrophilic granulocytes (NG) are the main drivers of pathological inflammation in COVID-19. Objective. To specify the mechanisms of immunopathogenesis of COVID-19 based on a comparative immunological study of the number and phenotype of CD16+SD62L+CD11b+CD63- and CD16+SD62L+CD11b+CD63+ subsets with an assessment of their effector functions against changing profile of NG-associated cytokines IL-8, IL-18, IL-17A, VEGF-A, IFNalpha, and IFNgamma. Patients and methods. In patients with moderate-to-severe and severe COVID-19, we determined IL-1beta, TNFalpha, IL-6, IL-8, IL-18, IL-17A, VEGF-A, IFNalpha, and IFNgamma (ELISA), the phenotype of CD16+SD62L+CD11b+CD63- and CD16+SD62L+CD11b+CD63+ subsets, NF-kappaB-NG (CYTOMICS FC500), phagocytically active NG (%), neutrophil extracellular traps (NETs), NG in apoptosis, and the activity of NADPH oxidase. Results. In COVID-19 against the background of IFNalpha and IFNgamma production blockade and high levels of NG-associated IL-8, IL-18, IL-17A, VEGF-A, a reduction in the number of mature and functionally active CD16brightSD62LbrightCD11bbrightCD63-NG subsets was revealed, as well as an increase in the number of CD16dimSD62LdimSD11bbrightCD63-NG subsets with an immunosuppressive phenotype and CD16brightSD62LbrightSD11bbrightCD63bright-NG subsets with high cytotoxic activity and ability to form NETs, a decrease in the percentage of phagocytically active NG and an increase in the activity of NADPH oxidase, NETs, and NG in apoptosis. Conclusion. IFNalpha deficiency provokes a hyperergic response of NG-associated cytokines, which leads to the formation of uncontrolled immune inflammation involving NG subsets with an immunosuppressive and cytotoxic phenotype, exacerbating the course of COVID-19. The use of recombinant IFNalpha-2b with antioxidants (Viferon) in the early stages of the disease can help to restore immune homeostasis, normalize the level of NG-associated cytokines, reduce NERTs, and achieve good clinical efficacy.Copyright © 2022, Dynasty Publishing House. All rights reserved.

Focus on Suicidal Behaviours - The experience of the11th EPA Summer School

Every year, the European Psychiatric Association organizes the EPA Summer School, an intensive program that aims to support and promote the education of young psychiatry professionals through numerous activities. The program returned to being an in-person event this year, after changes imposed by the COVID-19 pandemic over the last two years. From September 29 to October 2, 2022, young psychiatrists selected by the EPA Committee on Education, 21 in total, gathered together in Strasbourg, France, to attend the activities organized around the topic "Focus on Suicidal Behaviours - One Step Beyond." This year's event adopted a blended learning format;the participants were required to attend and complete a 6-week online course entitled "Focus on Suicidal Behaviours", before coming to the in-person sessions held by a distinguished group of lecturers. The activities designed during the training days allowed the participants to not only expand their knowledge about suicide and related issues but also to exchange experiences from different European countries, and they encouraged critical thinking about what can be done more or better. In addition, they encouraged the participants to get to know each other, to socialize, and to building relationships with each other. This article presents step-by-step the activities organized during the Summer School and also attempts to describe the way the participants experienced them. © 2023 John Libbey Eurotext. All rights reserved.;Chaque année, l'Association Européenne de Psychiatrie organise une Université d'été, un programme intensif qui vise à soutenir et à promouvoir l'éducation des jeunes professionnels de la psychiatrie par le biais de nombreuses activités. Elle a pu se tenir de nouveau en présentiel en 2022, après 2 ans d'organisation en distanciel, imposée par la pandémie de covid-19. Du 29 septembre au 2 octobre 2022, les jeunes psychiatres sélectionnés par le Comité d'éducation de l'EPA, 21 au total, se sont retrouvés à Strasbourg, en France, pour assister à cette formation autour du thème « Focus sur les conduites suicidaires - One step beyond ». L'événement de cette année a été que le format était un enseignement mixte. Pour débuter, la 1re partie de la formation s'est déroulée en ligne, sous la forme d'un MOOC « Focus sur les comportements suicidaires », pour une durée de 6 semaines, la seconde partie était la formation en présentiel avec des experts internationaux, sur une durée de 2 jours 1/2. Ces journées de formation ont permis aux participants non seulement d'élargir leurs connaissances sur le suicide et les questions connexes, mais aussi d'échanger autour des expériences de différents pays européens et d'encourager la réflexion critique sur ce qui peut être fait de plus ou de mieux, en termes de prévention et de soins. De plus, la possibilité de rencontres et d'échanges entre les participants a permis la création d'un réseau social européen unique. Cet article présente étape par étape les activités de formation organisées pendant l'université d'été de l'EPA et témoigne du vécu des participants. © 2023 John Libbey Eurotext. All rights reserved.;Cada año, la Asociación Europea de Psiquiatría organiza una Escuela de Verano, un programa intensivo cuyo objetivo es apoyar y promover la formación de jóvenes profesionales de la psiquiatría a través de una gran variedad de actividades. Ha podido volver a celebrarse en persona en 2022, tras 2 años de organización a distancia, impuesta por la pandemia de la covid-19. Del 29 de septiembre al 2 de octubre de 2022, los jóvenes psiquiatras seleccionados por el Comité de Educación de la EPA, 21 en total, se reunieron en Estrasburgo (Francia) para asistir a esta formación sobre el tema "Enfoque en las conductas suicida - One step beyond (Un paso más allá"). Lo más destacado del acto de este año fue que el formato era una formación combinada. Para empezar, la 1a parte de la formación fue online, en forma de MOOC "Focus en conductas suicidas", con un duración de 6 semanas, la segunda parte fue la formación presencial con expertos internacionales, con una duración de 2 días y medio. Estas jornadas de formación les permitieron a los participantes no sólo ampliar sus conocimientos sobre el suicidio y cuestiones afines, sino también intercambiar en torno a experiencias de distintos países europeos y fomentar el pensamiento crítico sobre qué más o mejor se puede hacer, en términos de prevención y asistencia. Además, la posibilidad de encuentros e intercambios entre los participantes permitió crear una red social europea única. Este artículo presenta paso a paso las actividades de formación organizadas durante la escuela de verano de la EPA y da fe de la experiencia de los participantes. © 2023, John Libbey Eurotext. Tous droits réservés. © 2023 John Libbey Eurotext. All rights reserved.

Primary immunodeficiency associated with a SAMD9L mutation

Background: SAMD9L is a tumor suppressor involved in regulating the proliferation and maturation of cells, particularly those derived from the bone marrow, and appears to play an important role in cerebellar function. It can be activated in hematopoietic stem cells by type I and type II interferons. It has been hypothesized to act as a critical antiviral gatekeeper regulating interferon dependent demand driven hematopoiesis. Gain of function mutations can present with an immunodeficiency due to transient severe cytopenias during viral infection. Case presentation: We report a 3-year-old boy born full term with a history of severe thrombocytopenia requiring transfusions, developmental delay, ataxia, seizure disorder, and recurrent severe respiratory viral infections. His infectious history was significant for respiratory syncytial virus with shock requiring extracorporeal membrane oxygenation complicated by cerebral infarction and a group A streptococcus empyema, osteomyelitis requiring a left below the knee amputation, and infections with rhinovirus, COVID-19, and parainfluenza requiring hospitalizations for respiratory support. Initial immunologic evaluation was done during his hospitalization for parainfluenza. His full T cell subsets was significant for lymphopenia across all cell lines with CD3 934/microL, CD4 653/microL, CD8 227/microL, CD19 76/microL, and CD1656 61/microL. His mitogen stimulation assay to phytohemagglutinin and pokeweed was normal. Immunoglobulin panel showed a mildly decreased IgM of 25 mg/dL, but normal IgA and IgG. Vaccine titers demonstrated protective titers to 12/22 pneumococcus serotypes, varicella, diphtheria, mumps, rubella, and rubeola. Repeat full T cell subsets 6 weeks later revealed marked improvement in lymphocyte counts with CD3 3083/microL, CD4 2101/microL, CD8 839/microL, CD19 225/microL, and CD1656/microL. A primary immunodeficiency genetic panel was ordered and positive for a heterozygous SAMD9L c.1549T>C (p.Trp517Arg) mutation classified as a variant of unknown significance. Discussion(s): This patient's history of severe viral infections, ataxia, thrombocytopenia, and severe transient lymphopenia during infection is suggestive of a SAM9DL gain of function mutation. Protein modeling done by the laboratory suggests this missense mutation would affect protein structure. The mutation found has been observed in individuals with thrombocytopenia. This case highlights the importance of immunophenotyping both during acute illness and once recovered.Copyright © 2023 Elsevier Inc.

Inherited deficiency of the OAS-RNase L pathway in children with MIS-C

Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1, OAS2, or RNASEL in five unrelated children with MIS-C. The cytosolic dsRNA-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the ssRNA-degrading RNase L. Consistent with the absence of pneumonia in these patients, epithelial cells and fibroblasts defective for this pathway restricted SARS-CoV-2 normally. This contrasted with IFNAR1-deficient cells from patients prone to hypoxemic pneumonia without MIS-C. Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNASEL deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or SARS-CoV- 2 stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-but not RNase L- deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by MAVS deficiency. Recessive OAS-RNase L deficiencies in these patients unleash the production of SARS-CoV-2-triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C.Copyright © 2023 Elsevier Inc.

Pericytes may facilitate SARS-CoV-2 entry into the nervous system

Objective: Although the neurological and olfactory symptoms of coronavirus disease 2019 have been identified, the neurotropic properties of the causative virus, severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2), remain unknown. We sought to identify the susceptible cell types and potential routes of SARS-CoV-2 entry into the central nervous system, olfactory system, and respiratory system. Method(s): We collected single-cell RNA data from normal brain and nasal epithelium specimens, along with bronchial, tracheal, and lung specimens in public datasets. The susceptible cell types that express SARS-CoV-2 entry genes were identified using single-cell RNA sequencing and the expression of the key genes at protein levels was verified by immunohistochemistry. We compared the coexpression patterns of the entry receptor angiotensin-converting enzyme 2 (ACE2) and the spike protein priming enzyme transmembrane serine protease (TMPRSS)/cathepsin L among the specimens. Result(s): The SARS-CoV-2 entry receptor ACE2 and the spike protein priming enzyme TMPRSS/cathepsin L were coexpressed by pericytes in brain tissue;this coexpression was confirmed by immunohistochemistry. In the nasal epithelium, ciliated cells and sustentacular cells exhibited strong coexpression of ACE2 and TMPRSS. Neurons and glia in the brain and nasal epithelium did not exhibit coexpression of ACE2 and TMPRSS. However, coexpression was present in ciliated cells, vascular smooth muscle cells, and fibroblasts in tracheal tissue;ciliated cells and goblet cells in bronchial tissue;and alveolar epithelium type 1 cells, AT2 cells, and ciliated cells in lung tissue. Conclusion(s): Neurological symptoms in patients with coronavirus disease 2019 could be associated with SARS-CoV-2 invasion across the blood-brain barrier via pericytes. Additionally, SARS-CoV-2-induced olfactory disorders could be the result of localized cell damage in the nasal epithelium.Copyright © Wolters Kluwer Health, Inc. All rights reserved.

Acceptabilité et faisabilité d'un module TCD-A multi-familles « tolérance à la détresse » proposé à des adolescents ayant un trouble de la personnalité borderline ou des troubles de la régulation émotionnelle

Le trouble de la personnalité borderline est un trouble psychiatrique fréquent qui apparaît à l'adolescence. La thérapie comportementale dialectique adaptée aux adolescents (TCD-A) a montré son efficacité dans la prise en charge psychothérapeutique des adolescents souffrant de conduites suicidaires ou d'auto-agressivité associées au trouble de la personnalité borderline. Au travers de notre étude nous avons souhaité explorer la faisabilité et l'acceptabilité, pour des adolescents présentant un TPL diagnostiqué ou des troubles de la régulation des émotions, d'un module TCD intitulé « tolérance à la détresse » proposé sur le mode d'un groupe multi-familles. Pour ce faire nous avons mis en place un groupe multi-familles de six adolescents et de leurs parents. L'acceptabilité et la faisabilité du protocole étaient excellentes. Les témoignages des adolescents et de leurs parents nous apportent des informations précieuses sur l'intérêt d'un tel groupe et sur les améliorations à introduire. La mise en place d'un tel groupe est une première en France et nous souhaitions montrer par notre étude pilote, sa faisabilité, son acceptabilité et ses effets afin de promouvoir son développement et son implémentation dans le contexte pédopsychiatrique français. Borderline personality disorder is a common psychiatric disorder emerging in adolescence. Dialectical Behavioral Therapy adapted to adolescents (DBT-A) has proven to be effective as a psychotherapeutic treatment for adolescents suffering from borderline-related behaviors, such as suicidal or self-aggressive behaviors. In our study, we were interested in exploring the feasibility and acceptability of a DBT-A module entitled "distress tolerance", which reduces borderline-related behaviors in borderline adolescents or undiagnosed adolescents who experience difficulties in regulating their emotions. To do this, we set up a pilot study with one multi-family treatment group of six adolescents and their parents. The treatment was fully accepted by all adolescents and parents with an excellent acceptability. Comments from adolescents and parents gave us valuable information about the great interest of a multi-family treatment group and potential improvements for its implementation. This is the first study exploring a DBT-A multi-family treatment group in France. It highlights its feasibility, acceptability and potential positive effects. Further studies are needed to promote the implementation and development of such interventions in the context of child and adolescent psychiatry in France. [ FROM AUTHOR] Copyright of Neuropsychiatrie de l'enfance & de l'Adolescence is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Mental, physical, and cognitive wellbeing during the COVID-19 pandemic: Data from Scotland and Japan

We present data from two studies examining how COVID-19 restrictions affected health behaviours (alcohol consumption, diet, sleep quality, and physical activity levels), mental wellbeing (negative mood) and cognitive function (decision making, attention, learning, working memory, and time perception) in association with sociodemographic factors. Study 1 assessed participants in Scotland and presents cognitive function data for five timepoints. Study 2 is transnational, assessing participants in Scotland and Japan. Data are stored as CSV files. Reuse may involve examining further effects of pandemic enforced social isolation or serve as baseline data when assessing social isolation in expeditions or ageing. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

LABORATORY PARAMETERS ASSOCIATED WITH CODIV-19 CYTOKINE STORM DEVELOPMENT

BackgroundSince the end of 2019, physicians became more and more familiar with SARS-CoV-2 infection and the variety of forms in which it may present and evolve. There have been a lot of studies trying to understand and predict why some patients develop a dysregulation of the immune response, with an exaggerated release of pro-inflammatory cytokines, called cytokine storm (1–4). There is scarce evidence in Romania regarding this aspect.ObjectivesThis study aims to verify the correlation between some laboratory parameters and the development of cytokine storm in SARS-CoV-2 infection in a cohort of over 200 patients admitted in a tertiary hospital from Romania, hoping that early identification of these risk factors of progression to a severe form of the disease can bring considerable benefit to patient care.MethodsThis is an analytical, observational, case-control study which includes 219 patients (all COVID-19 hospitalized patients on the Internal Medicine 3 department of Colentina Clinical Hospital, Bucharest, from 01 March 2020 to 1 April 2021). A series of data were collected, the laboratory parameters being the most important, including: albumin, lymphocyte (percentage), neutrophil (absolute value), aspartate aminotransferase, alanine aminotransferase, D-dimers, lactate dehydrogenase (LDH), anionic gap, chloremia, potassium and the BUN:creatinine ratio (BUN - blood urea nitrogen). The laboratory parameters used for the statistical analysis represent the average values of the first 7 days of hospitalization for those who did not develop cytokine storm, respectively until the day of its development, for the others. Patients were classified into these groups, those who developed cytokine storm, respectively those who did not have this complication taking into account the clinical and paraclinical criteria (impairment of respiratory function, elevations of certain markers 2-3 times above the upper limit of normal, those who died as a result of SARS-CoV-2 infection). Then Binary Univariate Logistic Regression was applied in order to verify the individual impact of every laboratory parameter on cytokine storm development. Furthermore, all laboratory parameters were subsequently included in the multivariate analysis, using the backward selection technique to achieve a model as predictive as possible.ResultsWe mention that the analysis of demographic data was previously performed, showing no statistically significant relationship between patient gender, age or comorbidities (history of neoplasm, lung diseases, cardiac pathology, obesity, type II diabetes and hypertension) and their evolution to cytokine storm. After performing binary univariate logistic regression we concluded that 8 of the 13 laboratory analyzes have had a significant change between groups (ferritin, PCR, albumin, Lymphocyte, Neutrophils, TGO, LDH, BUN:creatinine ratio). Only 150 patients were then included in the multivariate analysis. After the analysis, some of the variables lost their statistical significance, the final model including C-reactive protein, neutrophilia, LDH, ferritin and the BUN:creatinine ratio. This model correctly predicts the development of cytokine storm in 88% of cases.ConclusionHigh C-reactive protein, neutrophilia, LDH, ferritin and the BUN:creatinine ratio are risk factors for cytokine storm development and should be monitored in all COVID-19 patients in order to predict their evolution.References[1]Pedersen SF et all. SARS-CoV-2: A storm is raging[2]Mehta P et al. COVID-19: consider cytokine storm syndromes and immunosuppression[3]Hu B et al. The cytokine storm and COVID-19.[4]Caricchio R et al. Preliminary predictive criteria for COVID-19 cytokine stormAcknowledgements:NIL.Disclosure of InterestsNone Declared.

Evusheld Prophylaxis Improves Social Interactions, Anxiety, Depression, Agoraphobia, and Quality of Life in Blood Cancer Patients

Evusheld is a combination injection of tixagevimab and cilgavimab and is indicated for the pre-exposure prophylaxis of COVID-19 in adults and adolescents aged 12 years and older. Its use has been advocated for immunosuppressed individuals, such as blood cancer patients, although uptake varies significantly between countries. Despite extensive use internationally, there has been limited analysis of potential psychological benefits that vulnerable patients might gain from receiving this prophylactic medication. In this study we have quantified four key psychological health parameters in blood cancer patients who received Evusheld (EQ5D-3L quality of life score, DSM5 Agoraphobia score, Duke's Social Support Index and the hospital anxiety and depression score) and compared their responses with a control group of patients who did not receive Evusheld. We show that patients who opted for treatment had higher baseline markers of psychological stress and ill-health compared with non-treated individuals but that treatment with Evusheld significantly improved the psychological health of recipients and increased the level of physical social/work interactions over that of control patients. Although there are limitations with this small study, the findings strongly suggest that Evusheld prophylaxis can provide significant psychological benefits for vulnerable blood cancer patients who have significant anxiety about COVID-19 infection. [ FROM AUTHOR] Copyright of COVID is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

The impact of dynamic capabilities on SME performance during COVID-19

Dynamic capabilities (DCs) are a growing field of research within the scope of theoretical structures based on resource and strategic management. Given the demonstrated impact of DCs on company performance, it is important to study the effects of DCs on small and medium sized enterprises (SMEs) within the context of the COVID-19 pandemic. Hence, this research evaluates the role of DCs during the pandemic and its impact on the performance levels of SMEs. Analysing the responses of 209 SMEs using a structural equations model, we report that DCs positively affect company performance both prior to and during the pandemic. However, we also verify that while prior to the pandemic companies placed greater emphasis on the search for new opportunities, following the onset of the pandemic the focus shifted to getting their products to the market. These results contribute to the literature on strategic management and the DC based approach during periods of turbulence and pandemics.

Sentiment Analysis on Twitter Data of Omicron (B.l.l.529) using Natural Language Processing

The COVID pandemic is causing outrageous interference in everyday life and financial activity. Close to two years after the presence of COVID, WHO allotted the variety B.l.l.529 a variety of concern, named 'Omicron'. Online diversion data assessment is created and transformed into a more renowned subject of investigation. In this paper, a sizably voluminous heap of appraisals and assessments are culminated with online redirection information. The evaluations and appearances of Twitter electronic diversion stage clients are summarised and researched by considering sentiment analysis by utilising various natural language processing techniques based on positive, negative, and neutral tweets. All potential outcomes are considered for investigating the feelings of Twitter clients. For the most part, tweets are assessed clearly, and this assessment ensures the headway of this investigation study. Different kinds of analyzers are utilised and measured. The 'TextBlob Sentiment Analyzer' has given the highest polarity score based on positivity, negativity, and neutrality rates in terms of inspiration, pessimism, and impartiality. A total dataset is fully determined and classified with all the analyzers, and a comparative result is also measured to find the ideal analyzer. It is intended to apply boosting machine learning methods to increase the accuracy of the proposed architecture before further implementation. © 2022 IEEE.

New Developments in Climate Change, Air Pollution, Pollen Allergy, and Interaction with SARS-CoV-2

In recent years, the environmental impacts of climate change have become increasingly evident. Extreme meteorological events are influenced by climate change, which also alter the magnitude and pattern of precipitations and winds. Climate change can have a particularly negative impact on respiratory health, which can lead to the emergence of asthma and allergic respiratory illnesses. Pollen is one of the main components of the atmospheric bioaerosol and is able to induce allergic symptoms in certain subjects. Climate change affects the onset, length, and severity of the pollen season, with effects on pollen allergy. Higher levels of carbon dioxide (CO2) can lead to enhanced photosynthesis and a higher pollen production in plants. Pollen grains can also interact with air pollutants and be affected by thunderstorms and other extreme events, exacerbating the insurgence of respiratory diseases such as allergic rhinitis and asthma. The consequences of climate change might also favor the spreading of pandemics, such as the COVID-19 one.

What drives the performance and causality of green bond indices?

This paper empirically assesses the performance of green bond indices and the causality of that performance using a range of financial and commodity data. We present new insights from the novel application of datasets, neural networks and performance measurements. We find that green bond indices do not outperform the market when factors beyond market return are considered. We find that Brent crude oil has the most significant effect on certain indices, a finding that contrasts with other studies on green bonds. A greater sensitivity to oil prices and global green equities also evinces a negative impact on a green bond index's ability to outperform the market. For the first time, a linear causal relationship is established between Title Transfer Facility (TTF) returns and green bond index returns. Additionally, a fundamental shift in causal relationships is observed over the COVID-19 period. In this way, we contribute to the literature on sustainable green bonds and the impact of COVID-19. These insights provide more clarity to market participants for navigating the uncertainties of both the global energy transition and the postpandemic period. © 2023 Informa UK Limited, trading as Taylor & Francis Group.

The Impact of the Online Project-Based Learning on Students' Communication, Engagement, Motivation, and Academic Achievement

Purpose. Project-based learning (PBL) is a student-centered environment that emphasizes a dynamic classroom approach. It is founded on the idea that students gain a deeper understanding by actively tackling difficulties and issues from the real world. Students gain knowledge in a subject by devoting a significant amount of time to researching and solving a challenging question or interesting issue. Methods & Procedure. PBL was used in online classes during the pandemic of COVID-19. The study concentrated on projects that were created by students themselves under the guidance of teachers with the aim of determining their impact on their communication, engagement, motivation, and academic accomplishment in L2 acquisition context. The sample of the study that consisted of 100 EFL college students deployed this methodology in their weekly lectures. Results. The results show that PBL can have some positive effect on the entire spectrum of parameters under consideration as well as have a substantial impact on communication, engagement, motivation, and academic performance in online education. The findings clearly show that PBL can be a useful methodology for L2 acquisition and can provide students with various challenging activities and topics that increase their motivation and engagement, and thus, academic achievement. © The Author(s) 2023.

Using cfRNA as a tool to evaluate clinical treatment outcomes in patients with metastatic lung cancers and other tumors.

Aim: We report an exploratory analysis of cfRNA as a biomarker to monitor clinical responses in non-small cell lung cancer (NSCLC), breast cancer, and colorectal cancer (CRC). An analysis of cfRNA as a method for measuring PD-L1 expression with comparison to clinical responses was also performed in the NSCLC cohort. Methods: Blood samples were collected from 127 patients with metastatic disease that were undergoing therapy, 52 with NSCLC, 50 with breast cancer, and 25 with CRC. cfRNA was purified from fractionated plasma, and following reverse transcription (RT), total cfRNA and gene expression of PD-L1were analyzed by real-time polymerase chain reaction (qPCR) using beta-actin expression as a surrogate for relative amounts of cfDNA and cfRNA. For the concordance study of liquid biopsies and tissue biopsies, the isolated RNA was analyzed by RNAseq for the expressions of 13 genes. We had to close the study early due to a lack of follow-up during the Covid-19 pandemic. Results: We collected a total of 373 blood samples. Mean cfRNA PCR signals after RT were about 50-fold higher than those of cfDNA. cfRNA was detected in all patients, while cfDNA was detected in 88% of them. A high concordance was found for the expression levels of 13 genes between blood and solid tumor tissue. Changes in cfRNA levels followed over the course of treatments were associated with response to therapy, increasing in progressive disease (PD) and falling when a partial response (PR) occurred. The expression of PD-L1 over time in patients treated with immunotherapy decreased with PR but increased with PD. Pre-treatment levels of PD-L1 were predictive of response in patients treated with immunotherapy. Conclusion: Changes in cfRNA correlate with clinical response to the therapy. Total cfRNA may be useful in predicting clinical outcomes. PD-L1 gene expression may provide a biomarker to predict response to PD-L1 inhibition.

Golden berry leaf extract containing withanolides suppresses TNF-α and IL-17 induced IL-6 expression in HeLa Cells.

Inflammation, characterized by the overexpression of IL-6 in various tissues, has been reported as a symptom of coronavirus disease 2019 (COVID-19). In this study, we established an experimental system for overexpression of IL-6 in HeLa cells stimulated by TNF-α and IL-17, along with identification of anti-inflammatory materials and components from local agricultural, forestry, and fishery resources. We constructed a library of extracts from natural sources, of which 111 samples were evaluated for their anti-inflammatory activities. The MeOH extract of Golden Berry (Physalis peruviana L) leaf was found to exhibit strong anti-inflammatory properties (IC50 = 4.97 µg/mL). Preparative chromatography identified two active constituents, 4ß-hydroxywithanolide E (4ß-HWE) (IC50 = 183 nM) and withanolide E (WE) (IC50 = 65.1 nM). Withanolides are known anti-inflammatory ingredients of Withania somnifera, an Ayurvedic herbal medicine. P. peruviana leaves containing 4ß-HWE and WE should be considered as useful natural resources for anti-inflammatory products.

Clinical and inflammation marker features of cancer patients with COVID-19: data of Istanbul, Turkey multicenter cancer patients (2020-2022).

OBJECTIVE: We aimed to identify a rapid, accurate, and accessible biomarker in the early stages of COVID-19 that can determine the prognosis of the disease in cancer patients. METHODS: A total number of 241 patients with solid cancers who had a COVID-19 diagnosis between March 2020 and February 2022 were included in the study. Factors and ten different markers of inflammation were analyzed by year of diagnosis of COVID-19 and grouped by severity of infection. RESULTS: Hospitalization, referral to the intensive care unit (ICU), mechanical ventilation, and death were more frequent in 2020 than in 2021 and 2022 (mortality rates, respectively, were 18.8%, 3.8%, and 2.5%). Bilateral lung involvement and chronic lung disease were independent risk factors for severe disease in 2020. In 2021-2022, only bilateral lung involvement was found as an independent risk factor for severe disease. The neutrophil-to-lymphocyte platelet ratio (NLPR) with the highest area under the curve (AUC) value in 2020 had a sensitivity of 71.4% and specificity of 73.3% in detecting severe disease (cut-off > 0.0241, Area Under the Curve (AUC) = 0.842, p <.001). In 2021-2022, the sensitivity of the C-reactive protein-to-lymphocyte ratio (CRP/L) with the highest AUC value was 70.0%, and the specificity was 73.3% (cut-off > 36.7, AUC = 0.829, p = .001). CONCLUSIONS: This is the first study to investigate the distribution and characteristics of cancer patients, with a focus on the years of their COVID-19 diagnosis. Based on the data from our study, bilateral lung involvement is an independent factor for severe disease, and the CRP/L inflammation index appears to be the most reliable prognostic marker.

Identification of Flavonoids from Scutellaria barbata D. Don as Inhibitors of HIV-1 and Cathepsin L Proteases and Their Structure-Activity Relationships.

Scutellaria barbata D. Don (SB, Chinese: Ban Zhi Lian), a well-known medicinal plant used in traditional Chinese medicine, is rich in flavonoids. It possesses antitumor, anti-inflammatory, and antiviral activities. In this study, we evaluated the inhibitory activities of SB extracts and its active components against HIV-1 protease (HIV-1 PR) and SARS-CoV2 viral cathepsin L protease (Cat L PR). UPLC/HRMS was used to identify and quantify the major active flavonoids in different SB extracts, and fluorescence resonance energy transfer (FRET) assays were used to determine HIV-1 PR and Cat L PR inhibitions and identify structure-activity relationships. Molecular docking was also performed, to explore the diversification in bonding patterns of the active flavonoids upon binding to the two PRs. Three SB extracts (SBW, SB30, and SB60) and nine flavonoids inhibited HIV-1 PR with an IC50 range from 0.006 to 0.83 mg/mL. Six of the flavonoids showed 10~37.6% inhibition of Cat L PR at a concentration of 0.1 mg/mL. The results showed that the introduction of the 4'-hydroxyl and 6-hydroxyl/methoxy groups was essential in the 5,6,7-trihydroxyl and 5,7,4'-trihydroxyl flavones, respectively, to enhance their dual anti-PR activities. Hence, the 5,6,7,4'-tetrahydroxyl flavone scutellarein (HIV-1 PR, IC50 = 0.068 mg/mL; Cat L PR, IC50 = 0.43 mg/mL) may serve as a lead compound to develop more effective dual protease inhibitors. The 5,7,3',4'-tetrahydroxyl flavone luteolin also showed a potent and selective inhibition of HIV-1 PR (IC50 = 0.039 mg/mL).