Distinct profiles and kinetics of soluble infammatory markers in patients with acute and chronic HCV-infections and SARS-CoV-2-infections: Implications for the long-term consequences of viral infections?

Background and Aims Viral infections occur acutely but can also progress chronically, with the immune system having a central role in immunopathoge-nesis. The question arises whether all alterations in immune responses are reversible after viral elimination (spontaneously or by therapy). Therefore, the aim of this study is to compare soluble infammatory markers (SIM) during and after infection with SARS-CoV-2 and acute and chronic HCV-infections. Patients and Method Patients with acute HCV (n = 29), chronic HCV (n = 54), SARS-CoV-2 (n = 39) and 31 healthy-controls were included. Blood samples were tested at baseline, end of treatment/infection, and follow-up ( >= 9 months after baseline). IL-12p70, IL-1b, IL-4, IL-5, IL-6, IL-8, TNF, IFN-g, IL-10, IL-22, CXCL-10, MCP-1, MIP-1b, ITAC were quantified using the HD-SP-X Imaging and Analysis SystemTM. Results SIM profiles in patients with acute HCV were substantially elevated at baseline and the decrease during follow-up was considerably less compared to the SARS-CoV-2 cohort. In chronic HCV-patients, viral elimination by therapy resulted in a decrease in SIM, although not always to those of controls. Cirrhotic HCV patients had higher SIM levels after HCV elimination than non-cirrhotic chronic HCV-patients. In the SARS-CoV-2 cohort, most SIM returned to levels of controls 3 months after baseline. Conclusions SIM profiles and kinetics after viral elimination difer between blood-borne acute and chronic HCV- and respiratory SARS-CoV-2-infections. The immunologic imprint 9 months after cured HCV-infection (both acute and chronic) appears to be more pronounced than after SARS-CoV-2-infection. Further analysis is needed to correlate the SIM profle with the clinical pheno-type (long-HepC vs. long-COVID-19).

Number Soup: Case Studies of Quantitatively Dense News

Numbers don’t speak for themselves–yet taking numbers for granted (numerism) is widespread. In fact, journalists often rely heavily on numbers precisely because they are widely considered objective. As a team of journalists and social scientists, we undertook a qualitative exploration of clauses and entire news reports that are particularly quantitatively dense. The dense clauses were often grammatically complex and assumed familiarity with sophisticated concepts. They were rarely associated with explanations of data collection methods. Meanwhile, the dense news reports were all about economy or health topics, chiefly brief updates on an ongoing event (e.g., stock market fluctuations;COVID-19 cases). We suggest that journalists can support public understanding by: Providing more detail about research methods;Writing shorter, clearer sentences;Providing context behind statistics;Being transparent about uncertainty;and Indicating where consensus lies. We also encourage news organizations to consider structural changes like rethinking their relationship with newswires and working closely with statisticians. © 2022 Informa UK Limited, trading as Taylor & Francis Group.

A Randomised Evaluation of Low-Dose Ara-C Plus BCT-100 Versus Low Dose Ara-C in Older Patients with Acute Myeloid Leukaemia: Results from the LI-1 Trial

Background: Among patients with Acute Myeloid Leukaemia (AML) over the age of 60, a considerable number are not considered suitable for intensive remission-induction chemotherapy. Survival in these patients is poor, whether they are treated using hypomethylating agents or low-dose ara-C (LDAC). The possibility of combination therapy with additional agents represents an attractive option. Arginine metabolism plays a key role in AML pathogenesis (Mussai et al. Blood 2013);BCT-100 is a pegylated recombinant human arginase that leads to a rapid depletion in extracellular and intracellular arginine concentrations resulting in G0/G1 arrest, and subsequent death by necrosis. BCT-100 demonstrates significant activity as single-agent against AML cell lines, AML xenografts and primary AML blasts from newly diagnosed or relapsed patients (Mussai et al. Blood 2015). Importantly BCT-100 is synergistic in combination with cytarabine. Aims: To assess the efficacy of LDAC+BCT100 versus LDAC alone in patients aged 60+ unsuitable for intensive therapy, in a “pick a winner” design. This design allows several treatments to be assessed simultaneously in a randomised fashion, with the aim of doubling 2-year survival from 11% to 22% (HR 0.69), with interim assessments after 50 and 100 patients per arm are recruited. Methods: LDAC was given at 20mg BD SC on days 1-10 of each course. Patients randomised to the combination received LDAC as above with BCT-100 1600U/kg on Days 1, 8, 15 and 22 as a 1-hour intravenous infusion. Courses occurred at 4-6 week intervals. Toxicities were recorded using CTCAE version 3. Pharmacokinetic and biomarker samples were assessed in BCT-100 patients. Results here are based upon median follow-up of 3.8 months (range: 0.1 - 20.6 months) Results: Between September 2018 and December 2020, 83 patients were randomised. The trial was prematurely closed due to the COVID pandemic and did not reach the pre-planned first evaluation. Median age was 76.7 years (range 62-88). Overall, 65% were male;70% de novo AML, 23% secondary AML, and 6% high risk MDS;2% favourable, 59% intermediate, 23% adverse and 15% unknown/unreported cytogenetics. Median of 2 courses was delivered in either arm (mean 2 LDAC, 2 LDAC+BCT, range for both: 1-12). BCT-100 leads to a depletion of arginine from baseline in the majority of patients. Overall response (CR/CRi) was achieved in 12/81 patients (15%), (LDAC+BCT-100 15%, LDAC 15%, R 1.03 (0.30, 3.51),P=0.963). Thirty-day mortality was not significantly increased (18% vs 11%, HR 1.71 (0.50, 5.84), P=0.393;and 1-year survival showed no evidence of a difference (31% vs 30%, HR 1.28 (0.72, 2.25). Median overall survival time was 3.8 vs 6.4months;overall survival HR 1.11 (0.64, 1.90), P=0.715. The most common cause of death was resistant/recurrent disease: 12(46%) vs 16(59%). BCT-100 was not associated with any haematological toxicity;although rare grade 3/4 cardiac and hepatic events were reported, these were not significantly increased with BCT-100. Summary: The addition of BCT-100 to LDAC did not improve response rate or survival. BCT-100 was well tolerated with an acceptable toxicity profile. Further clinical evaluation of BCT-100 induced arginase depletion continues in a variety of malignancies. Acknowledgements: We are grateful to Blood Cancer UK for funding the trial and Bio-Cancer Treatment International for providing drug and additional support for this Investigator Initiated Study. Figure 1. OS All patients [Formula presented] Disclosures: Knapper: Jazz: Consultancy, Speakers Bureau;Pfizer: Consultancy, Speakers Bureau;Astellas: Ended employment in the past 24 months, Speakers Bureau;Novartis: Consultancy, Research Funding, Speakers Bureau. McMullin: Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Other: clinical trial support, Research Funding;Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Abb ie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;AOP Orphan: Research Funding, Speakers Bureau. Copland: Incyte: Honoraria, Research Funding, Speakers Bureau;Novartis: Honoraria, Speakers Bureau;Pfizer: Honoraria, Speakers Bureau;Cyclacel Ltd: Research Funding;Astellas: Honoraria, Speakers Bureau;Jazz: Honoraria, Speakers Bureau. Russell: Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding;Novartis: Speakers Bureau;Astellas: Membership on an entity's Board of Directors or advisory committees;Jazz: Research Funding, Speakers Bureau.

An Adaptive Blended Learning Approach in the Implementation of a Medical Neuroscience Laboratory Activities.

Background: The COVID-19 pandemic revealed existing gaps in the medical educational system that is heavily dependent on the presence of medical students and teachers in laboratory and class for instruction. This affects continuity in the implementation of the neuroanatomy component of the medical neuroscience laboratory activities during COVID-19. We hypothesized that pivoting wet laboratory neuroanatomy activities to online using an adaptive flexible blended method might represent an effective approach in the implementation of laboratory neuroanatomy activities during a pandemic. Methods: The current study describes an adaptive flexible blended learning approach that systematically mixes virtual face-to-face interaction activities with the online learning of brain structures, and the discussion of clinical cases. Learning materials are delivered through both synchronous and asynchronous modes, and Year 1 medical students learn neuroanatomy laboratory activities at different locations and different times. Student performances in the adaptive flexible blended learning approach were compared with the learning of similar activities during an in-person implementation of neuroscience laboratory activities. Results: The results of using this adaptive flexible blended learning approach provided an autonomous independent learning, self-study approach that broadened student performance such that we have more students scoring between 80 and 89%, whereas the in-person learning resulted in most of the students scoring > 90% in the medical neuroscience laboratory activities. Conclusion: An adaptive flexible blended learning approach that combined virtual face-to-face instruction using digital technology with online learning of neuroscience laboratory activities provided a unique educational experience for Year 1 medical students to learn neuroscience laboratory activities during the COVID-19 pandemic.

An Adaptive Blended Learning Model for the Implementation of an Integrated Medical Neuroscience Course During the Covid-19 Pandemic.

The implementation of an integrated medical neuroscience course by technologically pivoting an in-person neuroscience course to online using an adaptive blended method may provide a unique approach for teaching a medical neuroscience course during the Covid-19 pandemic. An adaptive blended learning method was developed in response to the requirements necessitated by the Covid-19 pandemic. This model combined pedagogical needs with digital technology using online learning activities to implement student learning in a medical neuroscience course for year one medical students. This approach provided medical students with an individually customized learning opportunity in medical neuroscience. The students had the complete choice to engage the learning system synchronously or asynchronously and learn neuroscience materials at different locations and times in response to the demands required to deal with the pandemic. Students' performance in summative and formative examinations of the adaptive blended learning activities were compared with the previous performance obtained the previous year when the contents of the medical neuroscience course were implemented using the conventional "face-to-face" learning approach. While the cohort of our students in 2019 and 2020 changed, the contents, sessions, volume of material, and assessment were constant. This enabled us to compare the results of the 2019 and 2020 classes. Overall, students' performance was not significantly different between the adaptive blended learning and the in-person approach. More students scored between 70% and 79% during the adaptive blended learning compared with in-class teaching, while more students scored between 80% and 89% during the in-person learning than during the adaptive blended learning. Finally, the percentage of students that scored >90% was not significantly different for both Years 2019 and 2020. The adaptive blended learning approach was effective in enhancing academic performance for high-performing medical students. It also permitted the early identification of underachieving students, thereby serving as an early warning sign to permit timely intervention.

Surveillance System for Monitoring Social Distance

In the light of recent events, an epidemic - COVID-19 which took the world by surprise and continues to grow day by day. This paper describes an idea to control the spread of disease by monitoring Social Distancing. As of now from where we stand, the only way to avoid further spreading is to maintain proper social distance. Combining the advanced detection algorithms such as SSD, YOLO v4, and Faster-RCNN along with pedestrian datasets we reached the desired conclusion of calculating the distance between two detected persons in a video and identifying whether the social distancing norm is followed or not. This method can be implemented in CCTV’s, UAV’s, and on any other surveillance system. The rapid advancements in technologies led to more precise and accurate values. © 2021, Springer Nature Singapore Pte Ltd.