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The novel coronavirus disease 2019 (2019-NCOV), caused by the novel coronavirus (2019-NCOV), is raging around the world and has become an important global public health problem threatening human health. Since the outbreak in 2019, as of early October 2022, the cumulative confirmed cases of COVID-19 have reached 615, 689, 999 and the cumulative death cases have reached 6, 526, 739. The top five countries with the most confirmed cases are the United States, India, France, Brazil, and Germany. Currently, many people worldwide are still at risk of morbidity and mortality from SARS-CoV-2 and COVID-19. In the absence of specific drugs, vaccination is undoubtedly the most effective way to block the spread of the virus. As of July 2022, 16 vaccines have been approved for marketing or emergency use, and more than 250 vaccines are under development, among which 167 are in phase III clinical trials. By September 2022, nine vaccines had been conditionally marketed or approved for emergency use in China. This paper mainly reviews the specific characteristics and research and development status of various COVID-19 vaccines, as well as their safety and effectiveness. In addition, the future trends and challenges of vaccine research and development are analyzed based on the current situation. © 2023 SPIE.
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Background Taletrectinib is a potent, next-generation, CNS-active, ROS1 tyrosine kinase inhibitor (TKI) with selectivity over TRKB. In previous reports from TRUST-I, taletrectinib showed meaningful clinical efficacy and was well tolerated in pts with ROS1+ NSCLC (n = 109) regardless of crizotinib (CRZ) pretreatment status. We report updated efficacy and safety data with ~1.5 yr follow-up. Methods TRUST-I is a multicenter, open-label, single-arm study with two cohorts: ROS1 TKI-naive and CRZ-pretreated. Pts in both cohorts received taletrectinib 600 mg QD. Key study endpoints included IRC-confirmed ORR (cORR), DoR, disease control rate (DCR), PFS, and safety. A pooled analysis of ORR, PFS, and safety including pts from additional clinical trials was also conducted. Results In the 109 pts from TRUST-I (enrolled prior to Feb 2022) the median follow-up was 18.0 mo in TKI-naive (n = 67) and 16.9 mo in CRZ-pretreated pts (n = 42). cORR was 92.5% in TKI-naive and 52.6% in CRZ-pretreated pts (table). Median DoR (mDoR) and mPFS were not reached. Intracranial-ORR was 91.6%;ORR in pts with G2032R was 80.0%. In a pooled analysis with phase I studies, ORR was 89.5% and 50.0% for TKI-naive and CRZ-pretreated pts, respectively;mPFS was 33.2 mo and 9.8 mo. In 178 pts treated at 600 mg QD, treatment-emergent adverse events (TEAEs) were 92.7%;most (64.0%) were grade 1-2. The most common TEAEs were increased AST (60.7%), increased ALT (55.6%), and diarrhea (55.6%). Neurological TEAEs (dizziness, 18.5%;dysgeusia, 12.4%) and discontinuations due to TEAEs (3.4%) were low. Further updated results will be presented. [Formula presented] Conclusions With additional follow-up, taletrectinib continued to demonstrate meaningful efficacy outcomes including high response rates, prolonged PFS, robust intracranial activity, activity against G2032R, and tolerable safety with low incidence of neurological AEs. Clinical trial identification NCT04395677. Editorial acknowledgement Medical writing and editorial assistance were provided by Arpita Kulshrestha of Peloton Advantage, LLC, an OPEN Health company, and funded by AnHeart Therapeutics, Inc Legal entity responsible for the study AnHeart Therapeutics, Inc. Funding AnHeart Therapeutics, Inc. Disclosure S. He: Financial Interests, Personal, Other, Employment: AnHeart Therapeutics. T. Seto: Financial Interests, Institutional, Research Grant: AbbVie, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly Japan, Kissei Pharmaceutical, MSD, Novartis Pharma, Pfizer Japan, Takeda Pharmaceutical;Financial Interests, Personal, Other, Employment: Precision Medicine Asia;Financial Interests, Personal, Speaker's Bureau, Honoraria for lectures: AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, Covidien Japan, Daiichi Sankyo, Eli Lilly Japan, Kyowa Hakko Kirin, MSD, Mochida Pharmaceutical, Nippon Boehringer Ingelheim, Novartis Pharma, Ono Pharmaceutical, Pfizer Japan, Taiho Pharmaceutical, Takeda Pharmaceutical, Towa Pharmaceutical. C. Zhou: Financial Interests, Personal, Other, Consulting fees: Innovent Biologics Qilu, Hengrui, TopAlliance Biosciences Inc;Financial Interests, Personal, Speaker's Bureau, Payment or honoraria: Eli Lilly China, Sanofi, BI, Roche, MSD, Qilu, Hengrui, Innovent Biologics, C-Stone LUYE Pharma, TopAlliance Biosciences Inc, Amoy Diagnositics, AnHeart. All other authors have declared no conflicts of interest.Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc.
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Mental stress has been recognized as an essential risk factor for hypertension. Therefore, experts specializing in cardiology, psychiatry, and Traditional Chinese Medicine organized by the Psycho-cardiology Group, College of Cardiovascular Physicians of Chinese Medical Doctor Association, and Hypertension Group of the Chinese Society of Cardiology proposed the expert consensus on the diagnosis and treatment of adult mental stress-induced hypertension in March 2021, which includes the epidemiology, etiology, diagnosis, and treatment of the mental stress-induced hypertension. This consensus will hopefully facilitate the clinical practice of this disorder. In addition, the COVID-19 pandemic has become one of the primary global sources of psychosocial stressors since the beginning of 2020, and the revision of this expert consensus in 2022 has increased the relevant content. This consensus consists of two parts. The sections of Part A include (I) Background and epidemiological characteristics, (II) Pathogenesis, and (III) Diagnosis. The sections of Part B contain (IV) Treatment recommendations, and (V) Prospects. This article presents Part B of the consensus. © 2022 Heart and Mind ;Published by Wolters Kluwer - Medknow.
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Mental stress has been recognized as an essential risk factor for hypertension. Therefore, experts specializing in cardiology, psychiatry, and Traditional Chinese Medicine organized by the Psycho-Cardiology Group of College of Cardiovascular Physicians of Chinese Medical Doctor Association and Hypertension Group of Chinese Society of Cardiology proposed the expert consensus on the diagnosis and treatment of adult mental stress-induced hypertension in March 2021, which includes the epidemiology, etiology, diagnosis, and treatment of the mental stress-induced hypertension. This consensus will hopefully facilitate the clinical practice of this disorder. In addition, the COVID-19 pandemic has become one of the primary global sources of psychosocial stressors since the beginning of 2020, and the revision of this expert consensus in 2022 has increased the relevant content. This consensus consists of Part A and Part B. Part A includes (I) Background and epidemiological characteristics, (II) Pathogenesis, and (III) Diagnosis and Part B includes (IV) Treatment recommendations and (V) Prospects. This part presents the content of Part A. © 2022 Heart and Mind ;Published by Wolters Kluwer - Medknow.
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The low-carbon development of air transport industry is of great significance for China to achieve the commitment of carbon peak and carbon neutrality goals. In order to improve the basic data of aviation CO2 emissions, this study continuously collected full flight information in China from January 2017 to December 2020, and established a flight information database and an aircraft-engine parameter database. On the basis of IPCC's Tier 3B accounting method, this study established a long-term aviation CO2 emissions inventory of China from 2017 to 2020 by calculating and accumulating CO2 emissions of each flight. And aviation CO2 emissions of various provinces and cities in China were calculated combined with spatial allocation method. The results showed that aviation CO2 emissions in China was 104.1, 120.1, 136.9, and 88.3 Mt in 2017, 2018, 2019, and 2020, respectively, with annual growth rates of 15.4%, 14.0%, and −35.3% in 2018, 2019, and 2020, respectively. Affected by the COVID-19 pandemic, aviation CO2 emissions in all 31 provinces and 93% of cities decreased in 2020 compared with 2019. China is in the stage of rapid development of air transport industry, and aviation fossil energy consumption and CO2 emissions have continued to grow in recent years. © 2022 Elsevier Ltd
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COVID-19 has developed chaos and uncertainty for small and medium enterprises (SMEs) causing mass downsizing. Under such uncertainty, innovation is key to survival and agility to growth. This study examines role of knowledge coupling and business process digitization (BPD) in sustaining innovation through market capitalizing agility (MCA) besides downsizing strategy. Data have been collected from top and mid management of Chinese manufacturing SMEs and analyzed with knowledge-based view and self-tuning model through Smart-PLS 4. Knowledge coupling positively contributes to MCA and innovation irrespective of downsizing strategy. Effect of BPD on innovation performance is same;however, insignificant on MCA in no-downsizing sample. Likewise, MCA positively influences innovation performance and positively mediates between knowledge coupling (BPD) and innovation performance only during downsizing. This study is first of its kind to establish mediating effect of MCA between knowledge coupling (BPD) and innovation performance during downsizing phase and offers significant theoretical and practical implications. JEL Classification: J63, O31
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Covid-19 pandemic has caused crisis and uncertainty which adversely influenced innovation performance of small and medium enterprises (SMEs). Innovation is a primary source of survival and growth in SMEs;therefore, this study aims to develop and empirically analyse conceptual model that sustains innovation performance of SMEs during the pandemic. This study integrates knowledge-based view (KBV) with a self-tuning model to examine Chinese manufacturing SMEs. Survey data of 306 responses were collected from the top and mid management and analysed through Smart-PLS 3. Results indicate a positive effect of knowledge coupling on innovation performance;besides, ambidexterity and market capitalising agility (MCA) positively mediate between knowledge coupling and SME innovation performance. This study contributes to KBV, self-tuning, strategy, innovation and crisis management literature. To practitioners, this study advises developing dynamic capabilities to sustain innovations during pandemic crisis. This is the earliest empirical examination to mediate the effect of knowledge coupling on innovation performance through ambidexterity and MCA during a crisis.
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Aims: NHSE/I and The RCS England have advocated that The separation of elective and surgical care is fundamental in recovering surgical services. It is suggested that The separation is physical and many Trusts are transforming pathways into elective and emergency hospitals. Croydon Hospital (CHS) have created an alternative, with 'a Hospital within a Hospital', separating these pathways within one estate, and considers whether this is a successful model for The future. Method(s): The day surgery unit On The ground floor was converted into an emergency centre with an ambulatory surgical hub, a hot clinic, clinical space, 4 emergency theatres and an USS room. The main theatre suite was converted into The Croydon Elective Centre (CEC) with a 12-bedded coronary catheter suite, a lift onto The second floor, 10 theatres, a 12 bedded children's day unit, Moorfields' eye unit, a new canteen, an admissions unit as well as a 28-bedded elective ward with a new 4-bedded level 1.5 critical care unit. Result(s): At The end of wave 1, 3,068 patients awaited treatment, an increase of 30.44% of baseline activity with theatre activity at 28% of normal activity. Activity resumed to 100% within 6 weeks of CEC go live. 2/9,606 patients were Covid-19 positive in The first year. During wave 2, 60% of pre-Covid-19 activity continued. Currently, 2,098 patients await treatment. Conclusion(s): The implementation of a surgical hub has supported The treatment of patients as well as provided continuous training opportunities for surgical and anaesthetic trainees as well as The theatre team.
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Introduction: We are faced with long waiting lists coupled with a loss of training opportunities for surgical trainees as a result of CoVID-19. It is imperative to ensure training opportunities are optimised and trainees are encouraged to contribute to The service recovery efforts we are faced with. Method(s): A pilot 'The hernia fest' was undertaken with The aim of training core trainees, supporting senior trainees as independent practitioners coupled with supporting The delivery of high volume, low complexity (HVLC) care. Parallel bespoke theatre lists with The grouping of specific cases (hernias), have been run with a consultant surgeon overseeing 2-3 lists. Each list includes a selected senior trainee who is suitable to train colleagues. Cases were screened prior to booking. All theatre staff were briefed On The purpose of The lists. All patients, trainees and theatre staff completed a questionnaire. Result(s): 50 hernia training cases were carried out over 15 sessions. 100% of patients were confident with their treatment and would recommend The service. 100% of trainees felt they had progressed in their operative competence and skill acquisition. 100%oftrainees were satisfied. Senior trainees enjoyed The responsibility of running an independent list. 100% of theatre staff felt they would participate in future lists. Conclusion(s): This model cultivates a learning environment whilst addressing waiting lists. The grouping of operations together allows for repetitive practice and may encourage rapid skill acquisition. We discuss lessons learnt and a proposed framework & checklist which can be applied to The future planning of such lists.
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Personal protective clothing (PPC) protects healthcare workers from infectious diseases such as COVID-19;however, there are limited technologies regarding the production of breathable and adaptive thermo-responsive personal protective clothing, which can improve the wearers' comfort. In this chapter, the development of such breathable and adaptive thermo-responsive personal protective clothing is described, and recent trends in material development for preparing such clothing are also presented. This review chapter also considers related technology for the fabrication of such breathable and adaptive thermo-responsive personal protective clothing. Finally, the future outlook regarding personal protective clothing is discussed. © 2022 Elsevier Ltd. All rights reserved.
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Epidemic viruses seriously affect human health and the normal operation of society, so it is particularly important to effectively kill viruses. In this work, a thermoelectric air disinfection system is studied. Utilizing the characteristics of semiconductor thermoelectric sheets with both cold and hot ends, the system can simultaneously sterilize the air by heating and reduce the temperature of the air by cooling. The measurement results show that the air temperature can be increased to 80 ℃ for disinfection, and then cooled to 35 ℃, and the total energy utilization rate of the system can reach up to 1.2. In addition, combined with the measurement results and numerical calculations, the parameters such as the number of thermoelectric element series, input power, air flow, and boundary insulation can be used to analyze their effects on the system performance. The system has broad potential applications in public health, medical care, and household disinfection. © 2022 中国物理学会 Chinese Physical Society.
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The coronavirus disease 2019 (COVID-19) continues to have a negative impact on healthcare systems around the world, though the vaccines have been developed and national vaccination coverage rate is steadily increasing. At the current stage, automatically segmenting the lung infection area from CT images is essential for the diagnosis and treatment of COVID-19. Thanks to the development of deep learning technology, some deep learning solutions for lung infection segmentation have been proposed. However, due to the scattered distribution, complex background interference and blurred boundaries, the accuracy and completeness of the existing models are still unsatisfactory. To this end, we propose a boundary guided semantic learning network (BSNet) in this paper. On the one hand, the dual-branch semantic enhancement module that combines the top-level semantic preservation and progressive semantic integration is designed to model the complementary relationship between different high-level features, thereby promoting the generation of more complete segmentation results. On the other hand, the mirror-symmetric boundary guidance module is proposed to accurately detect the boundaries of the lesion regions in a mirror-symmetric way. Experiments on the publicly available dataset demonstrate that our BSNet outperforms the existing state-of-the-art competitors and achieves a real-time inference speed of 44 FPS. The code and results of our BSNet can be found from the link of https://github.com/rmcong/BSNet. IEEE
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We analyzed the economic benefits versus safety risks of sharing anti-vascular endothelial growth factor (VEGF) vials during the coronavirus disease (COVID-19) pandemic. This single-center retrospective study analyzed the data of patients with neovascular age-related macular degeneration (nAMD), proliferative diabetic retinopathy (PDR) and retinal vein occlusion (RVO) who received anti-VEGF between January 2016 and July 2021 at Renmin Hospital, Wuhan University, China. Costs were compared of the two protocols of intravitreal injections (IVIs) of ranibizumab, aflibercept and conbercept after (i) splitting the vial content for use in two patients and after (ii) disposal of the remaining vial content after use in a single patient, with the COVID-19 outbreak considered as the demarcation point. The incidence rates of post-injection endophthalmitis (PIE) preand post-outbreak were analyzed. The mean cost of a single IVI increased by 33.3%, from 3917.67±71.69 to 5222.67±84.98 Chinese Yuan during the pandemic. The incidences of IVI-related culture-positive PIE were 0.0134% (3 in 22448) and 0.0223% (1 in 4479), respectively, before and after the pandemic (P=0.6532). We conclude that vial sharing of IVIs in a large clinical institution is not associated with increased PIE risk and can significantly reduce the cost of therapy. © 2022
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Inhibition of vascular endothelial growth factor (VEGF) has been widely applied in anti-neovascularization therapies. As a novel anti-VEGF agent, KH902 (conbercept) is designed to restrain pathological angiogenesis. However, the effects of KH902 on retinal hypoxia have not been well studied. In a mouse model of oxygen-induced retinopathy (OIR), we assessed retinal hypoxia at postnatal days 14 (P14) and P17, as well as retinal neovascularization (RNV) at P17. In addition, we evaluated the protein level of VEGF and galectin-1 (Gal-1). Changes of the neuroretinal structure were also examined. Our results indicated that KH902 could remit retinal hypoxia in OIR at P14 and P17, which was an exciting novel finding for KH902 function. Additionally, we confirmed that KH902 markedly reduces RNV. Our results indicated that administration of KH902 downregulated VEGF expression, as well as Gal-1. Damage of neuroretinal structure after KH902 injection was not observed, which was also an encouraging result. Our study suggests that KH902 plays a role in alleviating retinal hypoxia and that it could be used for the treatment of other ncovascular ocular diseases.
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Aims: The 2 week-wait pathway allows rapid referral and diagnosis of colorectal cancer. Gold standard investigation is lower gastrointestinal (lower GI) endoscopy, however less than 10% identify malignancy. This audit aims to identify the proportion of patient's with normal or benign findings at lower GI endoscopy who are discharged back to primary care. Methods: Retrospective audit of endoscopy reports and patient records was performed (September-October 2019). The results were highlighted to endoscopy and cancer services, and a biopsy results clinic was introduced in August 2020. In September 2020, a second cycle was performed on August 2020 endoscopies. Results: Cycle 1: 197/258 normal/benign endoscopies. 41/258 had normal findings but biopsies taken. 26/258 (11%) discharged from endoscopy, 117/258 (48%) discharged at first outpatient follow-up. Median time from referral to discharge at first outpatient follow-up was 56 days. Median time from referral to discharge from endoscopy was 10 days. Cycle 2: 81/107 normal/benign endoscopies, 14/107 had biopsies taken. 26/107 patients (27%) discharged at first follow-up. 17/107 (17%) discharged from endoscopy. Median time from referral to discharge at first outpatient follow-up was 48 days. Median time from referral to discharge from endoscopy was 12 days. Conclusions: Faster diagnosis service pathways (FDS) targets are not being met in patients with normal or benign endoscopy findings. In addition to the biopsy clinic, a prospective monthly audit has been implemented to monitor endoscopy discharges. COVID-19 caused widespread disruption in cancer services. With increased remote consultation going forward patient safety and satisfaction remains a priority.
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Coronavirus Infections/epidemiology , Pandemics , Pneumonia, Viral/epidemiology , COVID-19 , HumansABSTRACT
IntroductionThe COVID-19 pandemic has had an unprecedented impact with over 73 million confirmed cases and over1.6 million deaths globally at the time of this writing. Patients with severe SARS-CoV-2 infection can develop acute respiratory distress syndrome (ARDS). The illness is associated with tissue hemorrhage, causing local hemolysis and the release of heme in the lung. Extracellular heme is rapidly oxidized from Fe2+ to Fe3+, and has been reported to activate MYD88-mediated inflammatory signaling through Toll-like receptor (TLR)-4. SARS-CoV2 is a single strand RNA virus, which is sensed in part by endosomal TLR7/8 for initiating host innate responses. We hypothesized that heme impairs TLR7/8 mediated type 1 interferon response to coronaviruses, thereby worsening the infection. MethodsPeripheral blood mononuclear cells (PBMC) were isolated from each of 6 donor leukocytes, followed by CD14+ isolation. CD14+ monocytes were either studied directly or further differentiated into macrophages under the stimulation of M-CSF. Resiquimod (R848), an agonist for TLR7/8 in humans and TLR7 in a murine systems, was used as a mimic of coronaviruses. CD14+ monocytes and monocytes derived macrophages (MDM) were treated with hemin (heme containing Fe3+ iron), R848, or a combination of hemin and R848. Untreated cells were used as control. The production of proinflammatory cytokines including TNF, IL6, IFN-alpha, and IFN-beta, were measured by ELISA. The expressions of type 1 interferon stimulated genes (x MX1, ISG15, ISG20, and OASL) were assessed via quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Results Hemin alone has no effect on the expression of IL6, TNF, or type 1 interferon-stimulated genes by CD14+ monocytes and MDM, in comparison to untreated cells. In monocytes, hemin resulted in marked inhibition of type-I interferon responses induced by TLR7/8 agonism, but had no effect on IL6 or TNF production. In macrophages, hemin significantly downregulated the production of IL6, but did not affect TNF production or interferon signaling induced by TLR7/8 agonism. Conclusion Heme appears to impair the type 1 interferon response to coronavirus and proinflammatory cytokines productions in human mononuclear phagocytes. Furthermore, heme has different effects on human primary monocytes as compared to macrophages in vitro. We speculate that heme may thus worsens the infection caused by SARS-CoV2 in vivo. Supported by: NIH R01AI135128 and U01EB024501.