On the improvement of family services in public health events：a qualitative case study based on COVID-19 responses

Objective To understand the status of family services and residents’demands for services in Shanghai in order to construct and improve the key elements of family services in public health events. Methods We used a combining method of individual in-depth interviews and focused group interviews. The informants were domestic and foreign experts in public health, health services, education, safety, etc., community workers and residents. The interview questions were as follow：problems in family services, residents’demands and suggestions for family services, etc. Results We found 7 major family services problems in Shanghai’s response to public health events：The boundary of authorities and responsibilities were not clearly defined between the upper and lower departments. The team construction of public health professions at the community level was flawed. There were miscommunications between upper and lower medical institutions during the epidemic outbreaks. Residents were not aware of the available family services provided by their communities. Unnoticed insanitary spots still existed in public spaces, and the maintenance of residential emergence equipment needs to be strengthened. The public opinion guidance required further strengthening, and the elderly people lack an effective medium for information acquisition. The emergency plan of closed management to solve practical problems after Shanghai’s COVID lockdown was insufficient. The residents’demands included the following 6 aspects：comprehensive family services, supply and guarantee of basic living materials and special materials, professionals providing family services as a means of support, emergency medical services, receiving psychological intervention and understanding knowledge of mental health, security of food and food supply chain security. Conclusion ‘Government led’‘cross-border cooperation’‘clear executive body’and ‘based on the needs of residents’were key factors. Therefore, we suggest family services are included in the normalizing construction of government. © 2022 Fudan University. All rights reserved.

CheetahKG: A Demonstration for Core-based Top-k Frequent Pattern Discovery on Knowledge Graphs

Knowledge graphs capture the complex relationships among various entities, which can be found in various real world applications, e.g., Amazon product graph, Freebase, and COVID-19. To facilitate the knowledge graph analytical tasks, a system that supports interactive and efficient query processing is always in demand. In this demonstration, we develop a prototype system, CheetahKG, that embeds with our state-of-the-art query processing engine for the top-k frequent pattern discovery. Such discovered patterns can be used for two purposes, (i) identifying related patterns and (ii) guiding knowledge exploration. In the demonstration sessions, the attendees will be invited to test the efficiency and effectiveness of the query engine and use the discovered patterns to analyze knowledge graphs on CheetahKG. © 2022 IEEE.

Reduced Probability of 2020 June July Persistent Heavy Mei-yu Rainfall Event in the Middle to Lower Reaches of the Yangtze River Basin under Anthropogenic Forcing

Anthropogenic forcing has approximately halved the probability of 2020 June-July persistent heavy mei-yu rainfall event based on HadGEM3-GA6 simulations without considering the COVID-induced aerosol emission reduction.

Extradosed cable-stayed Peljesac Bridje in Croatia Fabrication of steel box girders and on-site installation

The new Peljeac Bridge and access road project, which links Mainland Croatia to the Peljeac Peninsula, is the most significant social infrastructure project in Croatia under construction at present. The bridge site lies in the highly active seismic region with ground acceleration a(g) = 0.34g and a maximum average ten-minute wind speed above 33.7 m/s. As a result, the execution class for the steel structure was judged to be EXC4 based on the recommended matrix in standard EN 1090-2, which defines execution classes according to consequence class, service category, and production category. The correspondingly determined quality level was class B+, which equates to quality class B under ISO 5817 with supplementary requirements for bridge decks from EN 1090-2. This article describes the whole fabrication process in the workshop, the long-distance transportation and the installation on the bridge site. To satisfy such high-quality technical requirements, the heavy steel structures were fabricated using a wide variety of mechanized equipment and automatic welding techniques. This helped to ensure a more efficient fabrication process and more consistent product quality. The length of the large side span segments was designed to suit the capabilities of the floating cranes and transit barges, thereby making on-site installation more efficient. Against the backdrop of the global Covid-19 pandemic, the contractor CRBC overcame seemingly unsurmountable obstacles beyond their control to successfully complete this challenging assignment in two years.

Real-World Evidence on Shift in Treatment Practice and Adoption of Novel Agents for Patients with Chronic Lymphocytic Leukemia in the United States

Introduction: Clinical availability of highly effective novel agents (including Bruton tyrosine kinase [BTK] and B-cell lymphoma 2 [BCL-2] inhibitors) is rapidly altering the therapeutic landscape of chronic lymphocytic leukemia (CLL) necessitating a review of treatment guidelines. However, there is limited real-world data to validate if the availability of these novel agents has translated to a true shift in treatment paradigm for patients treated in the community. As the majority of CLL patients are treated in non-academic community-based settings, we investigated the clinical adoption trends of commercially available FDA approved novel agents for treatment of CLL patients. In addition, given that the COVID-19 pandemic led to major alteration in clinical oncology practices, we further studied if this contributed to an alteration in the selection of therapeutic agents resulting in changes of CLL treatment patterns and the utilization of novel agents in the real-world setting. Thus, the objectives of this study were to examine the utilization pattern of various CLL therapies, as well as evaluate the pattern of adoption of novel agents for treatment and the impact of COVID. Methods: A retrospective observational study was conducted using the Flatiron Health database that comprised EHR-derived de-identified data. Adult patients (≥18 years) with newly diagnosed CLL from January 2014 to May 2021, with no prior treatment and who were continuously enrolled for at least 6 months before and 3 months after the index date, defined as the first date of CLL/SLL diagnosis were included. Treatment regimens were classified into seven mutually exclusive categories: bendamustine-based chemotherapy, other chemotherapy, anti-CD20-based therapy, ibrutinib, idelalisib, acalabrutinib and venetoclax. Further treatment categorization included chemotherapy vs. targeted therapy, and traditional IV vs. novel oral agents. The impact of the pandemic was examined by comparing the pre- and post-COVID cohorts (defined as 15 months pre- and post- of March 1, 2021). Descriptive analyses were conducted to examine the frequency of use of treatment regimens by quarter in each year, line of therapy and between different age, gender, US geographical region, insurance status, and race/ethnicity subgroups. Multivariable regression was conducted to examine factors associated with the likelihood of adoption of novel and oral agents. Statistical significance was determined at a p-value of less than 0.05. Results: A total of 3,037 newly diagnosed CLL patients (median age =73) were included in the study. Over half were male (62.3%), white (74.6%) and commercially-insured (54.1%). Patients were primarily treated in community practices (92%). Overall, a significant trend in adoption of novel agents was observed throughout the years following their approval (Figure 1A). Across the evaluation period, a significant decrease in chemotherapy use was observed from 61.3% (quarter 1, 2014) to 20% (quarter 2, 2021) in favor of targeted therapy as first-line therapy (Figure 1B). In contrast, the utilization of novel oral agents (vs. traditional IV agents) for first-line therapy increased from 9.5% to 70.9% for the same period (Figure 1C). Similar trends were observed for second-line and third-line therapies. Encouragingly, this change in treatment patterns was adopted comparably in all sociodemographic subgroups with no evidence of disparity. While there was no statistically significant difference between the pre- and post-COVID treatment landscape, the adoption of target and novel oral agents has been more pronounced with the COVID pandemic. Conclusions: Results from real-world data suggest that there is a clear shift towards the adoption of novel therapies with preference given to targeted agents and oral therapies in the US since 2014. Further research examining real-world outcomes associated with treatment regimens are needed to inform decision makers. [Formula presented] Disclosures: Chanan-Khan: Cellectar: Current equity holder in publicly-traded company;Alpha2 P armaceuticals, NonoDev, Starton: Current holder of stock options in a privately-held company;Ascentage: Research Funding;Alpha2 Pharmaceuticals: Patents & Royalties: Tabi;Ascentage, Starton, Cellectar, NonoDev, Alpha2 Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees;BeiGene, Jansen, Ascentage: Honoraria;BieGene, Jansen, Ascentage: Consultancy. Yang: BeiGene, Ltd.: Current Employment. Liu: BeiGene, Ltd.: Current Employment. Zimmerman: BeiGene, Ltd.: Current Employment. Tang: BeiGene, Ltd.: Current Employment. Ailawadhi: Karyopharm: Consultancy;AbbVie: Consultancy;Genentech: Consultancy;Takeda: Consultancy;GSK: Consultancy, Research Funding;Xencor: Research Funding;Cellectar: Research Funding;Medimmune: Research Funding;Ascentage: Research Funding;Pharmacyclics: Consultancy, Research Funding;Amgen: Consultancy, Research Funding;Janssen: Consultancy, Research Funding;Bristol Myers Squibb: Consultancy, Research Funding;BeiGene, Ltd.: Consultancy;Sanofi: Consultancy;Oncopeptides: Consultancy.

Fast core-based top-k frequent pattern discovery in knowledge graphs

Knowledge graph is a way of structuring information in graph form, by representing entities as nodes and relationships between entities as edges. A knowledge graph often consists of large amount of facts in real-world which can be used in supporting many analytical tasks, e.g., exceptional facts discovery and fact check of claims. In this work, we study a core-based top-k frequent pattern discovery problem which is frequently used as a subroutine in analyzing knowledge graphs. The main challenge of the problem is search space of the candidate patterns is exponential to the combinations of the nodes and edges in the knowledge graph.To reduce the search space, we devise a novel computation framework FastPat with a suite of optimizations. First, we devise a meta-index, which can be used to avoid generating invalid candidate patterns. Second, we propose an upper bound of the frequency score (i.e., MNI) of the candidate pattern that prunes unqualified candidates earlier and prioritize the enumeration order of the patterns. Lastly, we design a join-based approach to compute the MNI of candidate pattern efficiently. We conduct extensive experimental studies in real-world datasets to verify the superiority of our proposed method over the baselines. We also demonstrate the utility of the discovered frequent patterns by a case study in COVID-19 knowledge graph. © 2021 IEEE.

Apatinib in combination with camrelizumab, a humanized immunoglobulin G4 monoclonal antibody against programmed cell death-1, in patients with metastatic acral melanoma

Background: Patients(pts) with metastatic acral melanoma respond poorly to anti-PD-1 monotherapy. Apatinib, a vascular endothelial growth factor (VEGF) inhibitor, is a kind of antiangiogenic drugs which have shown synergistic therapeutic effects in combination with PD-1 blockade. We conducted this single-center, open label phase trial to evaluate the safety and efficacy of camrelizumab in combination with apatinib in advanced treatment-naïve acral melanoma pts. Methods: Eligible participants were adult pts (aged 18 to 75) with histologically confirmed unresectable stage or distant metastatic acral melanoma. Exclusion criterion included unknown primary melanoma, brain metastatic disease or previous use of anti PD-1 ab. Pts received camrelizumab at 200mg intravenous infusion every 2 weeks, in combination with apatinib 250 mg orally once a day. The primary endpoint was ORR according to RECIST 1.1 criteria, and the secondary endpoints were safety and RFS. Results: Thirty pts were enrolled from April 2019 to January 2021. Basic characteristics: the mean age was 56.7 years, 22 pts were at stage, 33.3% had an elevated LDH level. Median tumor burden was 45mm (10-187). Gene mutation: Nras 4, cKit 3, Braf 2. Up to January 2021, 27 pts could be evaluated, in which 2 pts got CR, 4 pts achieved PR, and 63% experienced tumor shrinkage. The ORR and DCR were 22.2% and 77.8%, respectively. With a median follow up time of 8.3 months, the median PFS was 8.0 months (95% CI, 3.68, 10.19), the one-year durable response rate was 83.3% and the duration of response time was still not reached. Univariate analysis showed high LDH level was negatively associated with PFS. Whole exome data of baseline tumor biopsies revealed a positive correlation between high copy number variation (CNV) plus high mutational load (TMB) and efficacy, and all of the 4pts with MDC1 gene mutation got tumor shrink and 2 got PR. 96.7% pts experienced treatment-related AEs (TRAEs), including hand foot syndrome in 40%, proteinuria in 40%, liver dysfunction in 36.7%, and hypothyroidism in 30%. The grade 3-4 TRAEs were 33.3%. AE-related permanent discontinuation occurred in only 13.3% pts. 6 pts had delays of treatment due to the COVID-19 epidemic. No dose-limiting toxicities and suspected unexpected AEs were observed in the combination. Conclusions: The combination of apatinib plus camrelizumab was tolerable and showed promising antitumor activities and PFS improvement in pts with treatment-naïve metastatic acral melanoma. The survival is still in follow up.

Antiviral and Anti-Inflammatory Treatment with Multifunctional Alveolar Macrophage-Like Nanoparticles in a Surrogate Mouse Model of COVID-19

The pandemic of coronavirus disease 2019 (COVID-19) is continually worsening. Clinical treatment for COVID-19 remains primarily supportive with no specific medicines or regimens. Here, the development of multifunctional alveolar macrophage (AM)-like nanoparticles (NPs) with photothermal inactivation capability for COVID-19 treatment is reported. The NPs, made by wrapping polymeric cores with AM membranes, display the same surface receptors as AMs, including the coronavirus receptor and multiple cytokine receptors. By acting as AM decoys, the NPs block coronavirus from host cell entry and absorb various proinflammatory cytokines, thus achieving combined antiviral and anti-inflammatory treatment. To enhance the antiviral efficiency, an efficient photothermal material based on aggregation-induced emission luminogens is doped into the NPs for virus photothermal disruption under near-infrared (NIR) irradiation. In a surrogate mouse model of COVID-19 caused by murine coronavirus, treatment with multifunctional AM-like NPs with NIR irradiation decreases virus burden and cytokine levels, reduces lung damage and inflammation, and confers a significant survival advantage to the infected mice. Crucially, this therapeutic strategy may be clinically applied for the treatment of COVID-19 at early stage through atomization inhalation of the NPs followed by NIR irradiation of the respiratory tract, thus alleviating infection progression and reducing transmission risk.

Novel strategy to prepare fluorescent polymeric nanoparticles based on aggregation-induced emission: Via precipitation polymerization for fluorescent lateral flow assay

Fluorescent polymeric nanoparticles (FPPs) attract much attention in the fluorescent lateral flow assay (FLFA) due to their favorable biocompatibility, excellent colloidal stability, and high detection sensitivity. However, conventional FPPs used in the FLFA suffer with aggregation caused quenching (ACQ) effect and complicated procedures for conjugating protein. Here, a novel strategy is developed for preparing the FPPs based aggregation-induced emission luminogens (AIEgen) through stabilized precipitation polymerization with maleic anhydride (MAH), styrene (St), AIE active TPE-1VBC as comonomers, which is initiated by 2,2-azobisisobutyronitrile (AIBN) in ethyl butyrate. Microenvironment alteration in the formation of FPPs is monitored by the self-reporting approach in a real-time manner, and effects of crosslinking on the alters are carefully investigated. With the merits of uniform and controllable sizes, high efficiency luminescence, and easy functionalized surface, the obtained FPPs is employed as the indicator for FLFA testing strips. Five FPPs with five sizes harvested from the polymerization are selected for studying the effects of particles' size on the flowing of FPPs in FLFA, which indicated that the FPPs with the diameter of 210 nm (FPPs@210) could be considered as the optimal FPPs for FLFA. Furthermore, the antibodies of COVID-19 were employed as the targets for demonstrating the feasibility of FPPs@210 for FLFA testing. This work provides a novel strategy to prepare ideal FPPs to construct FLFA strips, indicative of their great potential in bioassays. © 2021 the Partner Organisations.

Covid-19: An accidental catalyst for change in the canadian health care system

The needle has moved on the historically entrenched issues of national physician licensure, virtual health care, and our sick-at-work culture within weeks of the announcement of a global pandemic. Let’s ensure we retain these important advances. © 2020, British Columbia Medical Association. All rights reserved.

Scenario tree and adaptive decision making on optimal type and timing for intervention and social-economic activity changes to manage the COVID-19 pandemic

We introduce a novel approach to inform the re-opening plan followed by a post-pandemic lockdown by integrating a stochastic optimization technique with a disease transmission model. We assess Ontarios re-opening plans as a case-study. Taking into account the uncertainties in contact rates during different re-opening phases, we find the optimal timing for the upcoming re-opening phase that maximizes the relaxation of social contacts under uncertainties, while not overwhelming the health system capacity before the arrival of effective therapeutics or vaccines.