Scaling law of COVID-19 cases and city size and its evolution over time

Urban scaling law quantifies the disproportional growth of urban indicators with urban population size, which is one of the simple rules behind the complex urban system. Infectious diseases are closely related to social interactions that intensify in large cities, resulting in a faster speed of transmission in large cities. However, how this scaling relationship varies in an evolving pandemic is rarely investigated and remains unclear. Here, taking the COVID- 19 epidemic in the United States as an example, we collected daily added cases and deaths from January 2020 to June 2022 in more than three thousand counties to explore the scaling law of COVID- 19 cases and city size and its evolution over time. Results show that COVID- 19 cases super- linearly scaled with population size, which means cases increased faster than population size from a small city to a large city, resulting in a higher morbidity rate of COVID- 19 in large cities. Temporally, the scaling exponent that reflects the scaling relationship stabilized at around 1.25 after a fast increase from less than one. The scaling exponent gradually decreased until it was close to one. In comparison, deaths caused by the epidemic did not show a super-linear scaling relationship with population size, which revealed that the fatality rate of COVID-19 in large cities was not higher than that in small or medium-sized cities. The scaling exponent of COVID- 19 deaths shared a similar trend with that of COVID- 19 cases but with a lag in time. We further estimated scaling exponents in each wave of the epidemic, respectively, which experienced the common evolution process of first rising, then stabilizing, and then decreasing. We also analyzed the evolution of scaling exponents over time from regional and provincial perspectives. The northeast, where New York State is located, had the highest scaling exponent, and the scaling exponent of COVID- 19 deaths was higher than that of COVID-19 cases, which indicates that large cities in this region were more prominently affected by the epidemic. This study reveals the size effect of infectious diseases based on the urban scaling law, and the evolution process of scaling exponents over time also promotes the understanding of the urban scaling law. The mechanism behind temporal variations of scaling exponents is worthy of further exploration. © 2023 Science Press. All rights reserved.

Impact of the COVID-19 pandemic on patients with osteogenesis imperfecta

OBJECTIVES: On March 11, 2020, the WHO classified COVID-19 as a global pandemic. Measures to quell the pandemic included limiting non-essential activities including clinic visits and procedures. It is unclear if individuals with OI had disruptions in their access to healthcare or medications, and if such disruptions affected patients' symptoms. METHOD(S): A REDCap survey was distributed through the OI Foundation on August 31. Surveys completed through September 11 by individuals with OI or their caregiver are included in this analysis. Participants were asked to compare their symptoms and access to healthcare during the first 4 months of the pandemic to the 4 months before the pandemic. RESULT(S): 85 surveys were completed, and 6 were partially completed. The median age of participants was 40 years;35% were children. 32% of participants self-identified as having severe OI. Although most reported no changes in bone pain or fractures, 46% reported they were less likely to seek emergency medical care to treat a fracture, while 33% reported they were more likely to treat fractures at home (Fig 1A). There were delays in accessing all services, with greatest delays accessing dentistry (74%) and aquatic therapy (84%) (Fig 1B). 36% of participants receiving bisphosphonate infusions had delayed infusions because of the pandemic (Fig 1C). Of note, 50% of planned surgeries were delayed. CONCLUSION(S): Although many individuals with OI and their caregivers reported delays in accessing bone-related services/clinics during this 4-month period, there was not a concomitant increase in reported symptoms. This may have related to shelter-in-place restrictions and decreased activity. Limitations of this study include small sample size and potential selection bias because responses were obtained only from OIF members. To address these limitations, we are distributing the survey through healthcare providers of individuals with OI across major regions of the US from a variety of practice types including endocrine, orthopedics and multidisciplinary clinics. Furthermore, as the COVID-19 pandemic continues, we hope that this survey will provide information to address what aspects of healthcare may be in greatest need, as well as the modality through which services may be met. (Figure Presented).

Getting Students to (and Through) Advanced Math: Where Course Offerings and Content Are Not Adding Up. American Educator Panels. Research Report. RR-A827-10

This report uses Spring 2022 data from nationally representative surveys of principals and math teachers in kindergarten through grade 12 (K-12) to explore students' opportunities to prepare for and take advanced math. The authors found that small high schools, high schools in rural areas, and high schools that predominantly serve students from historically marginalized communities tend to offer fewer advanced math courses (e.g., precalculus, Advanced Placement math courses) and that uneven access to advanced math begins in middle school. K-12 teachers who work in schools that predominately serve students living in poverty are more likely to report skipping standards-aligned content and replacing the skipped content with concepts from previous grade levels. Also, more than half of K-12 math teachers said they need additional support for delivering high-quality math instruction, especially teachers who work in schools that serve predominantly high-poverty students. In the wake of the disproportionate impacts of the COVID-19 pandemic on students living in poverty and students of color, these results highlight a critical need for resources to support teachers and to increase student access to advanced courses. [For technical information about the surveys and analysis in this report, see "Learn Together Surveys. 2022 Technical Documentation and Survey Results. Research Report. RR-A827-9" (ED626092).]

Building back better: Granular energy technologies in green recovery funding programs

Summary Granular energy technologies with smaller unit sizes and costs deploy faster, create more jobs, and distribute benefits more widely than lumpy large-scale alternatives. These characteristics of granularity align with the aims of fiscal stimulus in response to COVID-19. We analyze the technological granularity of 93 green recovery funding programs in France, Germany, South Korea, and the UK that target £72.9 billion for low-carbon energy technologies and infrastructures across five emissions-intensive sectors. We find that South Korea's "New Deal” program is the most technologically granular with strong weighting toward distributed renewables, smart technologies, electric vehicle charge points, and other relatively low unit cost technologies that are quick to deploy. The UK has the least granular portfolio, concentrating large amounts of public money on small numbers of mega-scale energy projects with high implementation risks. We demonstrate how technological granularity has multiple desirable characteristics of green recovery: jobs, speed, and distributed benefits.

The factors associated with increased risk of hospitalisation in people with diabetes following SARS-CoV- 2 infection: A national replication study

Aim: People with type 1 or type 2 diabetes have a higher hospital admission rate following Covid-19 infection. This study aims to determine the degree to which the results of a previous study in Greater Manchester (GM) could be replicated in national-level data for England. Method(s): We focussed on the univariable regression analysis, which shows the association between admission and Covid-19 infection in people with diabetes. Modelling was conducted using logistic regression on data from the Covid-IMPACT database. Odds ratios were compared descriptively with the previous study. Result(s): In people with type 2 diabetes, factors associated with an increased risk of hospitalisation similar to the previous study were: older age, male sex, higher social deprivation, higher body mass index (BMI), higher cholesterol, lower eGFR, taking an ACE-inhibitor/ ARB, not taking metformin, and having asthma or hypertension. Patients with COPD, and those taking aspirin or clopidogrel also had increased risk, but the national data showed a greater risk (GM COPD odds ratio 1.89 [1.63-2.19] vs national 2.34 [2.28-2.40] / aspirin 1.49 [1.34-1.66] vs 1.66 [1.63-1.70] / clopidogrel 1.71 [1.47-1.98] vs 1.99 [1.94-2.04]). Similar results were observed in patients with type 1 diabetes. However, due to the increase in sample size, many factors which were previously not statistically significant have become significant, such as in type 2 diabetes BMI, low HDL-cholesterol. Conclusion(s): We have successfully replicated the methods, results and conclusions of our previous study in relation to factors associated with increased risk of hospital admission in diabetes individuals. Regional databases are suitable for large cohort studies, and in this instance produced similar results to a national database, validating our previous findings.

Using the "omnicell" automatic drug dispensing cabinet to monitor sedative drugs in a critical care unit

Introduction: Automatic drug dispensers are now widely used in critical care.1-2 They can provide information about dispensed drugs. Good practice in sedation restricts the use of sedatives and titrates doses to defined responses.3-4 Objectives: To extract drug dispenser issuing records for sedatives and link these to patient records to evaluate sedative use. Method(s): in October 2019, we introduced two Omnicell XT automated dispensing cabinets (Omnicell inc. CA, USA) into a 42 bedded general/neurological unit. ICNARC (Intensive care national audit and research centre) and CCMDS (Critical care minimum data set) data was collected using the Ward Watcher program. Dispenser issuing records for alfentanil, propofol and midazolam were obtained as Excel files for 13 months from January 2020. Output time stamps were converted to dates and times. Outputs were linked to outputs of the ICNARC and CCMDS records for the patients that the drugs were issued to. All the outputs had patients identified by their unique hospital numbers. These were used in Excel "power queries" to produce a spread sheet with a single row per patient. Multiple admissions used the first diagnosis, the final outcome and the total length of stay. The total dose of sedatives was calculated from ampoule dose and number. The duration of treatment was calculated from the first and last issues of the drug. ICNARC codes were used to identify the primary system in the admission diagnostic code and those patients admitted for COVID-19. Variables were compared using Chi Squared, Mann-Whitney U and Kruskal Wallis Tests. The significance of associations was established using Spearman's Rho. Linear regression was used to define relationships more clearly. Result(s): Table one summarises the patient characteristics with respect to all admissions during the study period and for patients who had had the studied drugs issued to them. Midazolam was used in fewer patients, they were more likely to be male, heavier (p>0001) and to die than patients receiving Propofol or Alfentanil (p>0.001). With respect to diagnostic groups, all the sedatives, particularly Midazolam (p<0.001), were more likely to be used in patients with COVID-19. The relationship between the dose of sedative drugs and patient age and weight was explored using the dose per advanced respiratory day. All three drugs had a significant but weak negative relationship with age, lower doses being given to older people (Propofol r2 = 0.02, p=0.01. Alfentanil r2 = 0.04, p=0.00. Midazolam r2 = 0.07, p=0.00.). There was also a weak but significant relationship between increasing dose of Propofol with patient weight (r2 = 0.02, p=0.01), but there was no relation between weight and doses of the other drugs. Conclusion(s): Information from automatic drug dispensers can be interpreted and combined with other datasets to produce clinically relevant information. The limited weak relationships between drug dose and age and weight suggests that sedative drugs could have been better titrated to response.

Nanosponges: As a Dynamic Drug Delivery Approach for Targeted Delivery

Recent advancements in nanotechnology have resulted in improved medicine delivery to the target site. Nanosponges are three-dimensional drug delivery systems that are nanoscale in size and created by cross-linking polymers. The introduction of Nanosponges has been a significant step toward overcoming issues such as drug toxicity, low bioavailability, and predictable medication release. Using a new way of nanotechnology, nanosponges, which are porous with small sponges (below one microm) flowing throughout the body, have demonstrated excellent results in delivering drugs. As a result, they reach the target place, attach to the skin's surface, and slowly release the medicine. Nanosponges can be used to encapsulate a wide range of medicines, including both hydrophilic and lipophilic pharmaceuticals. The medication delivery method using nanosponges is one of the most promising fields in pharmacy. It can be used as a biocatalyst carrier for vaccines, antibodies, enzymes, and proteins to be released. The existing study enlightens on the preparation method, evaluation, and prospective application in a medication delivery system and also focuses on patents filed in the field of nanosponges.Copyright © 2023 The Authors.

The impact of virtual site visits on programmatic accreditation

Introduction: While programmatic and institutional accreditation remain the vital components of a quality education, the associated costs of a site visit can be excessive, especially when the technology is available to accomplish this process virtually. In the wake of the COVID-19 global pandemic, it also became evident that a virtual site visit was the only viable means to accredit diagnostic medical sonography programs, given safety concerns for site visitors. Method(s): The study followed a mixed method, quasi-experimental design. This virtual site visits includes all learning concentrations (e.g. general sonography, adult cardiac sonography, and vascular technology) along with programs offering a multi-concentration educational program (i.e. combinations of any the listed learning concentrations). This research was based on the three quantitative questions and a fourth qualitative question. Result(s): The data analyses confirmed the McEwan and Walsh theory that the virtual accreditation site visit is a viable option given the many possibilities of communication technologies available today. This cost-saving alternative has the potential to reshape the rigorous accreditation process while saving educational institutions the expense of the on-site visit which was noted by the program directors. Conclusion(s): A future study of this kind could be enhanced by using a larger sample size than 28 programs that participated in this study. Take home message: In an era of cutting costs and maximising efficiency while still upholding the integrity of the programmatic accreditation, the virtual site visit does maintain the effectiveness and efficiency of the accrediting process.

Do free-floated shares and board characteristics influence corporate risk disclosure? An empirical analysis on conventional banks in a developing country

PurposeThis study aims to explore the status and drivers (including free-floated shares, board size, rule duality and board independence) of corporate risk disclosure (CRD) for the conventional listed banks in the Egyptian stock market from 2010 to 2021, which include the country's major political upheavals and the COVID-19 pandemic. Design/methodology/approachThis study based on a sample of 117 annual reports of sampled banks from 2010 to 2021. RD index of Al-Maghzom (2016) was developed and adopted to quantify CRD using an unweighted scoring system. The multiple linear regression model was used to validate the hypotheses. FindingsThe analysis shows that the COVID-19 pandemic increased insignificantly disclosure of all risks except for segment risks. In addition, findings reveal that all sampled banks adhere highly to the requirements of mandatory RD, with a low level of adherence to voluntary RD. Moreover, the analysis concluded that the board size and free-floating shares positively affect the disclosure of financial, operational, general information. Research limitations/implicationsThe study's limitations include the content analysis methodology, reliance on annual reports, emphasis on financial and non-financial risks, focus on listed conventional banks in Egypt. Practical implicationsCurrent study's findings are more likely to be useful for many parties. It informs investors about the characteristics of the boards' directors of Egyptian listed banks that disclosed risk information. Banks should disclose more comprehensive risk information. For academics, the current study's limitations can be considered in their future research. Originality/valueThis work fills a new research area in which there is relatively little research in emerging financial markets that adds new evidence to the relationship between RD and both free-floating shares and board characteristics, particularly in Egypt.

Case Report of Succesful Multidisiplinary Treatment for Patient with Metastatic Lung Cancer and Relapsed/Refractory Chronic Lymphatic Leukemia/Small Lymphocytic Lymphoma

Introduction: Croatian National Cancer Registry of Croatian Institute for Public Health reported that in year 2020 lung cancer was the second most common cancer site diagnosed in men with 16% and the third most common in women with 10% incidence among all cancer sites. Unfortunatelly lung cancer has the highest mortality in both men and women. Haematological malignancies had 7% share in all malignancies in both male and female cances cases. In 2020 190 newly diagnosed cases of lymphatic leukemia in men and 128 cases in women were reporeted, meaning 1.5 and 1.2% of all malignancies, respectively. Chronic lymphatic leukemia (CLL) is an advanced age disease and incidence increases with age. Impaired immunity, T and B cell dysfunction in CLL, chromosomal aberations, long-term immunosuppressive therapy and genetic factors can all cause secondary malignancies. Co- occurence of solid tumors and CLL is very rare. Although patiens with CLL have an increased risk of developing second primary malignancies including lung carcinoma, the data about their clinical outcomes are lacking. Parekh et al. retrospectively analyzed patients with simultaneous CLL and lung carcinoma over a 20-year period, and they found that ~2% of patients with CLL actually developed lung carcinoma. The authors claimed that up to 38% of patients will also develop a third neoplasm more likely of the skin (melanoma and basal cell carcinoma), larynx (laryngeal carcinoma) or colon. Currently there are no specific guidelines for concurrent CLL and non-small cell lung carcinoma (NSCLC) treatment. Usually, when the tumors are diagnosed simultaneously, treatment is based to target the most aggressive malignancy, as the clinical outcomes depend on the response of the tumor with the poorest prognosis. For this reason, a multidisciplinary approach is mandatory. Case report: A patient with history of coronary heart disease, myocardial infarction and paroxysmal atrial fibrillation was diagnosed in 2019 (at the age of 71) with B chronic lymphocytic leukemia with bulky tumor (inguinal lymph nodes 8x5 cm), stage B according to Binet, intermediate risk. He was treated with 6 cycles of chemoimmunotherapy (rituximab/cyclofosfamid/fludarabine). In 10/2019 remission was confirmed, but MSCT described tumor in the posterior segment of upper right lung lobe measuring 20x17 mm and bilateral metastases up to 11 mm. Bronchoscopy and biopsy were performed, and EGFR neg, ALK neg, ROS 1 neg, PD-L1>50% adenocarcinoma was confirmed. He was referred to Clinical Hospital Center Osijek where monotherapy with pembrolizumab in a standard dose of 200 mg intravenously was started in 01/2020. Partial remission was confirmed in October 2020. Immunotherapy was discontinued due to development of pneumonitis, dysphagia and severe weight loss (20kg), but without radiologically confirmed disease progression. At that time he was referred to our hospital for further treatment. Gastroscopy has shown erosive gastritis with active duodenal ulcus, Forrest III. Supportive therapy and proton pump inhibitor were introduced. After complete regression of pneumonitis, improvement of general condition and resolution of dysphagia, no signs of lung cancer progression were found and pembrolizumab was reintroduced in 12/2021. Hypothyroidism was diagnosed in 01/2021 and levothyroxine replacement ther apy was started. In 03/2021 he underwent surgical removal of basal cell carcinoma of skin on the right temporal region with lobe reconstruction. From 02/2021, when pembrolizumab was reintroduced, regression in tumor size was continously confirmed with complete recovery of general condition. He was hospitalized for COVID 19 infection in 09/2021, and due to complications pembrolizumab was discontinued till 11/2021. Lung cancer immunotherapy proceeded till 11/2022, when Multidisciplinary team decided to finish pembrolizumab because of CLL relapse. CLL was in remission till August 2022 when due to B symptoms, lymphcytosis, anemia and generalized lymphadenopathy, hematological workup including biopsy of cervical lymph node was performed and CLL/SLL relapse was confirmed. Initially chlorambucil was introduced, but disease was refractory. Based on cytogenetic test results (IGHV unmutated, negative TP53) and due to cardiovascular comorbidity (contraindication for BTK inhibitors) venetoclax and rituximab were started in 01/2023. After just 1 cycle of treatment normal blood count as well as regression of B symptoms and peripheral lymphadenopathy occured, indicating the probability of complete disease remission. In our patient with metastatic lung adenocarcinoma excellent disease control is achieved during 41 month of treatment in first line setting. Furthermore, relapsed/refractory CLL/SLL is currently in confirmed remission. Conclusion(s): Successful treatment of patients with multiple primary malignancies is based on multidisciplinarity, early recognition and management of side effects, treatment of comorbidities with the aim of prolonging life, controlling symptoms of disease and preserving quality of life.

Study of musculoskeletal problems among long-term computer users in Ahmedabad City

Background: COVID-19 made many changes in life of persons and even after post COVID era these changes are integral to our life. Some of the changes were online classes, work from home, and online gaming. Computer work leads to static position of neck, shoulders, and upper limbs for extended hours. This leads to higher risk of developing visual, musculoskeletal and psychological problems. Aims and Objectives: The present study was carried out to determine prevalence of musculoskeletal health disorders, assess work distribution, and their probable interaction with musculoskeletal health problems in computer users of Ahmedabad city. Material(s) and Method(s): A cross-sectional study was carried out over a period of 1-year time among 800 participants to study the musculoskeletal problems among computer users. Result(s): Out of 800 participants, 76.75% of participants had any computer related musculoskeletal problem. If participants work more than 4 h in a single spell prevalence of musculoskeletal problems was 82.95%. Regular exercise has significant role in preventing computer-related musculoskeletal problems. Conclusion(s): Computer-related musculoskeletal problems have relation with number of hours spent in single spell, total daily working hours, and years of computer-related work.Copyright © 2023, Mr Bhawani Singh. All rights reserved.

Moderating effect of project size on the relationship between COVID-19 safety protocols and economic performance of construction projects

PurposeThe COVID-19 health crisis has brought about a set of extra health and safety regulations, and procedures to the construction industry which could influence projects' economic performance (EP). The aim of this paper is to examine the effect of adopting COVID-19 safety protocols on construction sites on the economic performance (EP) of construction projects.Design/methodology/approachEmploying the survey method using a structured questionnaire, data were collected from small- and large-sized construction projects in Nigeria and analysed using partial least squares structural equation modelling (PLS-SEM) technique.FindingsThe findings reveal that job re-organization and sanitization have negative significant effects on EP, while social distancing and specific training have no effect on EP. Furthermore, project size moderates the relationship between job re-organization, sanitization, specific training and EP with the stronger effect on the relationships observed in big projects, except for the relationship between sanitization and EP where the moderating relationship is stronger in small projects. However, there is no significant moderating effect of project size on the relationship between social distancing and EP.Practical implicationsAs construction project sites continue to operate amidst strict safety protocols, this study offers theoretical and practical insights on how construction projects can adhere to the safety protocols while performing economically.Originality/valueThe originality of this study's findings stems from the fact that it is among the first to provide greater insight on how construction projects have fared economically considering the impact of the various COVID-19 protocols.

The impact of deprivation on Respiratory Support Unit outcomes in COVID-19 patients, and highlights from wave 2 data in Portsmouth

Background: The second wave of the COVID-19 pandemic caused significant demand for beds capable of delivering enhanced respiratory support. NHS England recommended the use of CPAP for patients with COVID-19 respiratory failure, a treatment which can be offered outside of a critical care facility, and on a Respiratory High Care/ Support Unit (RSU). The enhancement of Portsmouth's RSU provided CPAP and NIV for patients with COVID-19 respiratory failure. With our intensive care facilities at 300% their normal capacity, this greatly alleviated bed pressures on critical care. Varied levels of deprivation exist in Portsmouth's dense population. Deprivation has an impact on overall health, however the effect of postcode on outcomes for people going onto support for COVID-19 respiratory failure, is unknown. Method(s): Retrospective cohort analysis of consecutive patients admitted to Respiratory Support Unit during the second wave of the COVID-19 pandemic, from 02/11/2020 to 31/01/2021. 227 patients were included in the study with 8 removed due to incomplete data, all of the patients received respiratory support in the form of CPAP or NIV. We collected multivariate data including biochemical markers, demographics, oxygenation status, co-morbidities and outcomes. Outcomes measured were: 1) Death in RSU, 2) Discharge from RSU or 3) Intubation and Ventilation. To measure deprivation, we linked a persons postcode to an area called an LSOA (Lower-layer Super Output Area). These are small areas of similar population size, each of which has a deprivation score (ie. top 10%, to the lowest 10% areas of deprivation in the UK). This is measured using an 'index of multiple deprivation'. An individual's outcome from the RSU was then analysed in relation to the deprivation score allocated to their postcode. Result(s): We observed a significant number of patients discharged from RSU, without needing invasive mechanical ventilation. 80/219 were discharged directly. 45/219 died in RSU, and 94 were eventually admitted to ITU. The average stay on CPAP or NIV before needing admission to ITU was 3 days. Some biochemical markers which stood out in relation to the outcomes described were as follows: average LDH, D-dimer and Troponin levels were higher in those who were admitted to intensive care. In patients who died, the PCT was significantly higher on average when compared to the other two groups. In the group who were discharged, mean lymphocyte count was >1, in the other two groups this was <1. From our observations in Portsmouth, there is a negative correlation between deprivation and lower aged individuals admitted for COVID-19 related respiratory support. Overall, we also saw disproportionate representation of those from the most deprived 50% of the UK in our respiratory support unit. Conclusion(s): CPAP and NIV can effectively be used in an RSU during a spike of COVID-19, to safely minimise demand on critical care services. Deprivation may have an impact on outcomes in patients needing respiratory support related to COVID-19. Deprivation levels may help predict risk of needing enhanced respiratory support in certain age groups. Multiple biochemical markers may be of prognostic value in COVID-19.

Optimization and Characterization of Quercetin Vitamin C Nano-Phytosome Formulation

Objective: To design an optimal formulation for quercetin and vitamin C nano-phytosome. Method(s): Nano-phytosomes are prepared by the thin layer hydration technique using a 2-level-5-factor design experimental. A total of 32 experimental formulas were used for data analysis. The ratio of quercetin: soy lecithin (X1), the ratio of quercetin: cholesterol (X2), stirring speed (X3), stirring temperature (X4), and stirring time (X5) were used as independent factors, while globule size as a dependent factor. Data analysis was carried out by Design Expert12 application. Characterization of the optimal formula included physicochemical evaluation, globule size analysis, zeta potential, polydispersity index, entrapment efficiency, Transition Electron Microscopy (TEM) analysis, and FTIR analysis. Result(s): The optimal formula consisted of quercetin: vitamin C: lecithin: cholesterol ratio of 1: 1: 1.046: 0.105 mol;stirring speed 763.986 rpm;stirring time of 59 min, at temperature 51.73 degreeC which produced 59.26 nm average globule size, PDI value 0.66;zeta potential value-35.93+/-0.95 mV and average SPAN value 0.61. This formulation showed entrapment efficiency of quercetin 91.69+/-0.18 % and vitamin C 90.82+/-0.13 %. The TEM and FITR analysis showed the morphological of the globules and interactions between the drugs, soy lecithin, and cholesterol to form nano-phytosomes. Conclusion(s): The conditions to obtain the optimal formula for quercetin vitamin C nano-phytosome consisted of quercetin: vitamin C: lecithin: cholesterol ratio of 1: 1: 1.046: 0.105 mol;stirring speed 763.986 rpm;stirring time of 59 min, and at temperature 51.73 degreeC.Copyright © 2023 The Authors.

Enoxaparin Sodium Biosimilar in the Prophylactic Treatment of Veinous Thromboembolism and Thromboembolic Disease: Prophyvar Study

Objectives: Varenox is the first locally manufactured and approved biosimilar in Algeria. It is an enoxaparin sodium (ES) with established good analytical characterization and manufacturing quality control. The aim of the PROPHYVAR study was to generate real-life data in routine practices and to assess the safety and tolerability in the prophylaxis of venous thromboembolism (VTE). Method(s): This is an observational, prospective, multicenter study, conducted between April 2021 and May 2022. The primary safety outcome was the incidence of Adverse Events (AEs) related to the study drug. A sample size of 500 patients was calculated to estimate the proportion of patients with AEs. Assuming that approximately 10% will be lost to follow-up or not evaluable, 550 patients were needed to describe the impact of Varenox use. Result(s): The study was conducted in 25 different sites in Algeria, in 4 therapeutic areas: ICU, orthopedic surgery, obstetrics and nephrology;550 patients were included and received at least one injection of Varenox. The mean age was 47 years, women in majority (62.5%). The patients were overweight or obese (53%), with a history of arterial hypertension (25%), diabetes (7.5%) and renal failure (6.4%). Reasons for hospitalization were mainly fracture (15.5%), pregnancy (8.3%), COVID-19 (7%) or cancer (7%). The majority of patients were treated at prophylactic dose of 0.4ml (80%) or 0.6ml (10%). The median duration of follow-up was 24 days. A total of 38 patients experienced at least one AE (6.9%, CI95=[4.9%;9.4%]). Related AEs were reported in 10 patients (1.8%), mainly in nephrology (N=7 arterio-venous fistula). VTE events were reported in 6 patients (1.1%, CI95=[0.2%;2%]). Conclusion(s): This study suggests that Varenox is safe in the prophylaxis of VTE. To our knowledge this is the first large study describing the use of ES in current medical practice in Algeria.Copyright © 2023

Immunotherapy: SYNERGISTIC PERITONEAL ANTI-TUMOR EFFECT OF ALLOCETRAOTS, A CELLULAR IMMUNE-THERAPY, IN COMBINATION WITH IMMUNE CHECKPOINT INHIBITORS/CHEMOTHERAPY, THROUGH IN-VIVO REPROGRAMMING OF MACROPHAGES AND DENDRITIC CELLS

Background & Aim: Immune checkpoint inhibitors (ICI) revolutionized solid tumor treatment, however, in many tumors only partial response is achieved. Allocetra-OTS has an immune modulating effect on macrophages and dendritic cells and showed an excellent safety profile in patients including patients with sepsis and Covid-19. Here we investigated the anti-tumoral effect of Allocetra-OTS cellular therapy, in peritoneal solid tumor animal models. Methods, Results & Conclusion(s): Allocetra-OTS is manufactured from enriched mononuclear fractions and induced to undergo early apoptosis. Balb/c mice were inoculated intraperitoneally (IP) with AB12 (mesothelioma) with pLenti-PGK-V5-Luc-Neo and treated with anti- CTLA4 with or without Allocetra-OTS. Mice were monitored daily for clinical score and weekly using IVIS (Fig.1). Kaplan-Meier log rank test was done for survival. For Allocetra-OTS preparation, enriched mononuclear fractions were collected by leukapheresis from healthy eligible human donors and induced to undergo early apoptosis. Anti- CTLA4 standalone therapy significantly improved survival (Fig.2) from mean 34+/-9 to 44.9 +/-20 days. However, OTS standalone therapy was non-inferior and improved survival to 52.3 +/-20 days. Anti-CTLA4 + Allocetra-OTS combination therapy, ameliorated survival to 86.7+/-20 days with complete cancer remission in 60-100% of mice. Similar anti- tumoral effects of Allocetra-OTS were seen in mesothelioma model in a combination therapy with either anti-PD1 or cisplatin and using anti-PD1 in ID8 ovary cancer model. Based on single cell analysis confirmed by flow cytometry and pathology, the mechanism of action seems to be related or at least associated with an increase in f/480high peritoneal macrophages and a decrease in recruited macrophages, and to f/480high infiltration of the tumor. However, further studies are needed to confirm these observations. During IP tumor progression, Allocetra-OTS as a standalone therapy or in combination with ICI, or cisplatin, significantly reduced tumor size and resulted in complete remission in up to 100% treated mice. Similar results were obtained in ID8 ovary cancer. Based on excellent safety profile in > 50 patients treated in prior clinical trials for sepsis and Covid-19, Phase I/II clinical trial of Allocetra-OTS plus chemotherapy has started and three patient already recruited. A second phase I/II clinical trial of Allocetra- OTS plus anti-PD1, as a second- and third-line therapy in various cancers, was initiated in Q1 2023. [Figure presented]Copyright © 2023 International Society for Cell & Gene Therapy

Outcomes and mortality in a newly implemented ECMO center in Northeast Brazil during pandemic

Objectives: To evaluate the outcomes and risk factors associated with mortality of patients cannulated on ECMO in the context of covid infection during the pandemics in a newly implemented ECMO center Methods: This was a unicentric observational retrospective study performed at Real Hospital Portugues, in Recife, state of Pernambuco, Brazil. All consecutive patients with laboratory confirmed SARS-CoV-2 infection cannulated for VV-ECMO or VA-ECMO for severe ARDS from march 2020 to december 2021 were included retrospectively. Patients recieving ECMO for isolated refratory cardiogenic shock were excluded. Descriptive statistics and association tests were used to analyze characteristics, management and patient outcomes during that period. Result(s): In our cohort of 47 ECMO for covid associated ARDS (CARDS), 39 patients (83%) were admitted by our emergency department. 8 patients (17%) had been transferred from other hospitals as soons as they had been cannulated. 32 patients (68%) were male, median age was 50 years (18-69). Mean body mass index was 31 (21,4-46,3). 37 patients (78%) had at least 1 comorbidity. Major bleeding occurred in 34 (72%) patients. Venous thromboembolism and hemolysis ocurred in 19 (40%) and 13 (23%) patients, respectively. When we compared treatments before ECMO initiation (imunoglobulin, tocilizuman, nitric oxide, neuromuscular blockade and proning), proning was associated with better survival (RR 0,67 IC 0,46-0,97 p 0,029). The mean duration in mechanical ventilation until ECMO cannulation was 9,69 days and mean time in ECMO was 23 days. The 90- day mortality was approximately 72%. Conclusion(s): The only variable associated with a better chance of survival was proning before ECMO. Our mortality (72%) is higher than reported from a recent meta-analysis of 1986 ECMO patients implanted during the first pandemic year(37,1%). However it is similar to a German populational registry of covid patients receiving VV-ECMO (73%). Althought it;s impossible to make causal inferences with such a design and sample sizes, we believe that describing the experience of smaller and newly implemented ECMO centers serves as motivation to improve quality and also to plan for future episodes of pressure on health system.

Genetic associations from the Long COVID-19 Host Genetics Initiative contribute to understanding of the genetics of prolonged symptoms in COVID-19

Background/Objectives: One of the most remarkable features of SARS-CoV-2 infection is that a large proportion of individuals are asymptomatic while others experience progressive, even lifethreatening acute respiratory distress syndrome, and some suffer from prolonged symptoms (long COVID). The contribution of host genetics to susceptibility and severity of infectious disease is well-documented, and include rare monogenic inborn errors of immunity as well as common genetic variation. Studies on genetic risk factors for long COVID have not yet been published. Method(s): We compared long COVID (1534) to COVID-19 patients (96,692) and population controls (800,353) using both questionnaire and EHR- based studies. First meta-analysis of 11 GWAS studies from 8 countries did not show genome-wide significant associations. Result(s): Testing 24 variants earlier associated to COVID-19 susceptibility or severity by COVID-19 Host Genetics Initiative showed genetic variation in rs505922, an intronic variant in ABO blood group gene, to be associated with long COVID compared to population controls (OR = 1.16, 95% CI: 1.07-1.27, p = 0.033). (Within-COVID analysis gave similar OR, but was not significant after conservative Bonferroni correction (OR = 1.17, 95% CI: 1.06-1.30, p = 092)). Conclusion(s): The first data freeze of the Long COVID Host Genetics Initiative suggests that the O blood group is associated with a 14% reduced risk for long COVID. The following data freezes with growing sample sizes will possibly elucidate long COVID pathophysiology and pave the way for possible treatments for long lasting COVID symptoms.

Research on the 6XS6 of the SARS-CoV-2 Spike Protein

The 6XS6 is the structure of the SARS-CoV-2 spike protein. The physiological role of the spike protein is relative to the respiratory syndrome coronavirus and has a stronger infect on the human body than the ancestor virus. The purification of the 6XS6 is in the homo sapiens cell by the affinity chromatography, PBS supplemented and Size Exclusion chromatography. At last, using the Cryo-Electron Microscopy to see the structure. This paper is using the D614G mutation to illustrate the structure of the 6XS6. The N-terminal domain and C-terminal domain of the 6XS6 protein are ALA27 and VAL1137. Furthermore, the mutation doesn't have the hydrogen bond because the Asp614 is substituted by the Gly614, and the molecule that interacts with the Ala 647 may occur. While the 6XS6 structure has lots of non-covalent and disulfide bonds. Comparing the structure of the 6XS6 and 6VXX, both are glycoproteins, have three monomers, have two subunits, and have the same category of expression and classification. The different conformations of the two structures can affect the binding ability with the ACE2. This paper can help the researchers to further understand the structure and function of the 6XS6 which can be used in future experiments. © 2023 SPIE.

Association of state-level COVID-19 mortality rates with real-world progression and real-world overall survival among patients with advanced non-small cell lung cancer, 2020-2022

Background: The COVID-19 pandemic impacted the delivery of cancer care and outcomes in the United States (US). We examined the association between time-varying state-level weekly COVID19 mortality and progression-free survival (rwPFS), time to progression (rwTTP), and survival (rwOS) among pts with advanced non-small cell lung cancer (advNSCLC). Method(s): This retrospective study used the nationwide Flatiron Health electronic health recordderived de-identified database. The cohort included community oncology pts diagnosed with advNSCLC between March 1, 2020 and December 31, 2021 (follow-up through March 30, 2022). We extracted US data on COVID-19 deaths from the COVID-19 Data Repository by the Center for Systems Science and Engineering at Johns Hopkins University. We calculated state-level weekly COVID-19 death rates as weekly COVID-19 deaths per state population size from the 2019 American Community Survey. We categorized rates into quintiles based on all weekly rates during the observation period. Analyses were restricted to treated pts and indexed to start of first-line therapy. For rwPFS analyses, first occurrence of progression or death was considered an event, and pts were censored at last clinic note date. For rwTTP, only progression (not death) was considered an event, and pts with no event were censored at last clinic note date. For rwOS analyses, pts who did not die were censored at last structured activity. We used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between weekly time-varying state-level COVID-19 mortality rates and outcomes of rwPFS, rwTTP, and rwOS, adjusted for age at diagnosis, race/ethnicity, and state. Result(s): Among 7,813 advNSCLC pts, the median age at diagnosis was 70 years, the majority of the cohort was non-Hispanic White (59%), had non-squamous cell histology (68%) and a history of smoking (87%). Compared to pts living in states with the lowest quintile of COVID-19 mortality rates (Q1), pts living in states with the highest COVID-19 mortality (Q5) had worse rwOS (Q5 vs. Q1: HR 1.46, 95% CI 1.26-1.69) and rwPFS (Q5 vs. Q1: HR 1.18, 95% CI 1.05-1.33). No association was observed with rwTTP (Q5 vs. Q1: HR 1.05, 95% CI 0.90-1.22). Conclusion(s): In this study of real-world oncology data, we demonstrated the use of publicly-available COVID-19 mortality data to measure the time-varying impact of COVID-19 severity on outcomes in pts with advNSCLC. Higher state-level COVID-19 mortality rates were associated with worse rwOS and rwPFS among advNSCLC pts. The association with increased mortality among pts with advNSCLC may be related to COVID-19-related mortality or other factors such as pre-existing comorbidities which were not explored in this study.