ABSTRACT
Overall survival (OS) is considered the standard clinical endpoint to support effectiveness claims in new drug applications globally, particularly for lethal conditions such as cancer. However, the source and reliability of OS in the setting of clinical trials have seldom been doubted and discussed. This study first raised the common issue that data integrity and reliability are doubtful when we collect OS information or other time-to-event endpoints based solely on simple follow-up records by investigators without supporting material, especially since the 2019 COVID-19 pandemic. Then, two rounds of discussions with 30 Chinese experts were held and 12 potential source scenarios of three methods for obtaining the time of death of participants, including death certificate, death record and follow-up record, were sorted out and analysed. With a comprehensive assessment of the 12 scenarios by legitimacy, data reliability, data acquisition efficiency, difficulty of data acquisition, and coverage of participants, both short-term and long-term recommended sources, overall strategies and detailed measures for improving the integrity and reliability of death date are presented. In the short term, we suggest integrated sources such as public security systems made available to drug inspection centres appropriately as soon as possible to strengthen supervision. Death certificates provided by participants' family members and detailed standard follow-up records are recommended to investigators as the two channels of mutual compensation, and the acquisition of supporting materials is encouraged as long as it is not prohibited legally. Moreover, we expect that the sharing of electronic medical records and the legal disclosure of death records in established health registries can be realized with the joint efforts of the whole industry in the long-term. The above proposed solutions are mainly based on the context of China and can also provide reference for other countries in the world. © 2022 The Authors
ABSTRACT
Background Identification of CD8+ T-cell epitopes is critical for the development of immunotherapeutics. Existing methods for empirical determination of peptide binding are time-intensive, expensive and highly specialized. Mass spectrometry, the predominant high-throughput approach for MHC-I ligand discovery, is unable to easily interrogate defined subsets of proteins. Thus, we sought a high-throughput, accessible method for the identification of MHC-I ligands derived from user chosen, synthetically encoded sources of peptides. Here we present EpiScan, a programmable genetic strategy to identify MHC-I ligands amongst predetermined starting pools comprising >100,000 peptides. Methods To accomplish this, we used CRISPR-Cas9 to create 'EpiScan cells' that lack both endogenous MHC-I and short peptides in ER. Then, separate lentiviral introduction of an MHC-I allele and a single exogenous short peptide into the ER restores cell surface MHC-I levels according to the affinity of the peptide to the chosen MHC-I allele. We exploited the programmability of EpiScan to screen 12 different MHC-I alleles with large peptide libraries including the entire SARSCoV- 2 proteome. Results These screens uncovered an unappreciated role for cysteine that increases the number of predicted ligands by 12- 21%, revealed affinity hierarchies by analysis of biased-anchor peptide libraries, and identified conserved, high-affinity, T-cell reactive SARS-CoV-2 epitopes. Using these data, we generated and iteratively refined peptide binding predictions to create EpiScan Predictor, or ESP. ESP performed comparably to other state-of-the-art MHC-I peptide binding prediction algorithms while not suffering from underrepresentation of cysteine-containing peptides. Overall, the new specificities identified by EpiScan and ESP increase the number of peptides predicted to bind MHCs by over 15% on average. This significantly expands the potential human epitope landscape, facilitating epitope discovery efforts and the design of immunotherapeutics. Conclusions Our work significantly expands the potential human epitope landscape, facilitating epitope discovery efforts and the design of immunotherapeutics. .
ABSTRACT
Objective: To investigate the gastrointestinal (GI) manifestations of COVID-19 and retrospectively analyze the clinical characteristics of COVID-19 patients with GI symptoms. Methods: Data of 137 COVID-19 inpatients treated in Renmin Hospital of Wuhan University from February 1 to February 29, 2020 were collected. Patients were divided into GI group and Non-GI group according to the presence of digestive system abnormalities and gastrointestinal symptoms before and during admission. General data, clinical data, and relevant laboratory examination results of 137 patients were collected. SPSS 23.0 software was used for statistical analysis to compare the differences of various indicators between the two groups. Results: There was no statistically significant difference between the clinical data and the clinical manifestations of fever and dry cough between the GI group and the Non-GI group (P>0.05). The proportion of patients with fatigue in the GI group was higher than that in the Non-GI group (P<0.001). The proportion of critically ill patients was greater than that of the Non-GI group (P=0.011), and the proportion of GI combined with hypertension, diabetes, cardiovascular disease and chronic liver disease was higher than that of the Non-GI group (all P<0.05). GI group mortality rate was much higher than that of Non-GI group (P<0.001). Patients with GI group had higher white blood cell count and neutrophil count than Non-GI (P<0.001). The proportion of neutrophils, lymphocytes as well as lymph between the two groups had no statistical difference (P>0.05). The proportion of monocytes in the GI group was lower than that in the Non-GI group (P=0.033). There was no statistical difference in platelet count and C-reactive protein level between the two groups (P>0.05). LDH, TBIL, and Urea levels of GI group were higher than those of Non-GI group (P<0.05). There was no statistical difference in other cardiac, liver and kidney function tests, PT and APTT values between the two groups (P>0.05), but D-dimer in GI group was higher than in Non-GI group (P<0.001). Conclusion: Gastrointestinal symptoms are common in COVID-19 patients, and patients with other underlying diseases are at greater risk for developing gastrointestinal symptoms. COVID-19 patients with gastrointestinal symptoms progress more rapidly, have a higher mortality rate, and exhibit certain concomitant symptoms and laboratory tests that are specific to COVID-19. Therefore, more attention should be paid to the digestive system abnormalities and gastrointestinal symptoms in COVID-19 patients during clinical work. © 2021, Editorial Board of Medical Journal of Wuhan University. All right reserved.
ABSTRACT
Not only did COVID-19 give rise to a global pandemic, but also it resulted in an infodemic comprising misinformation, rumor, and propaganda. The consequences of this infodemic can erode public trust, impede the containment of the virus, and outlive the pandemic itself. The evolving and fragmented media landscape, particularly the extensive use of social media, is a crucial driver of the spread of misinformation. Focusing on the Chinese social media Weibo, we collected four million tweets, from December 9, 2019, to April 4, 2020, examining misinformation identified by the fact-checking platform Tencent-a leading Chinese tech giant. Our results show that the evolution of misinformation follows an issue-attention cycle pertaining to topics such as city lockdown, cures and preventive measures, school reopening, and foreign countries. Sensational and emotionally reassuring misinformation characterizes the whole issue-attention cycle, with misinformation on cures and prevention flooding social media. We also study the evolution of sentiment and observe that positive sentiment dominated over the course of Covid, which may be due to the unique characteristic of "positive energy" on Chinese social media. Lastly, we study the media landscape during Covid via a case study on a controversial unproven cure known as Shuanghuanglian, which testifies to the importance of scientific communication in a plague. Our findings shed light on the distinct characteristics of misinformation and its cultural, social, and political implications, during the COVID-19 pandemic. The study also offers insights into combating misinformation in China and across the world at large.
ABSTRACT
During COVID-19, with a heavy sprayer filled with disinfectant, the risk of infection for epidemic prevention personnel has been increased by long-term environmental disinfection. In order to reduce the burden and save energy of human, this paper proposed a Wheel-Legged Robotic Limb (WRL) for the carriers. The mass of WRL is only 1.77 kg. The WRL has one rigid robotic limb located below the sprayer, which can provide active supporting force for the sprayer. The WRL adopts force closed-loop control method to ensure the system provide an expected supporting force. The system performance was evaluated including standing and walking at 5 km/h, under three experimental conditions included: 1) with a sprayer, 19.41 kg (SPRAYER), 2) with the powered WRL, 22.18 kg (WRL_ON) and 3) with the unpowered WRL, 22.18 kg (WRL_OFF). When the supporting force is set as 80 N, the experimental results show that the WRL_ON condition has reduced the vertical load force on the human, the vertical ground reaction force of human feet, and the metabolic power by 41.28%, 8.03%, and 17.46%, respectively, during standing, and also reduced by 32.29%, 8.08% and 18.92%, respectively, during walking, compared to SPRAYER condition. IEEE
ABSTRACT
Not only did COVID-19 give rise to a global pandemic, but also it resulted in an infodemic. The consequences of this infodemic can erode public trust and outlive the pandemic. The evolving and fragmented media landscape, particularly the extensive use of social media, is a crucial driver of the spread of misinformation. We collected four million Weibo posts on the Chinese social media from 12/2019 to 4/2020, examining misinformation identified by a fact-checking platform. Our results show that the evolution of misinformation follows an issue-attention cycle, pertaining to topics such as city lockdown, cures, and school-reopening. Sensational-reassuring misinformation characterizes the whole issue-attention cycle, with misinformation on cures and prevention flooding social media. We also study the evolution of sentiment and observe that positive sentiment dominated during COVID-19, which may be due to the unique characteristic of "positive energy'' on Chinese social media. Lastly, we study the media landscape during Covid via a case study on a controversial unproven cure, which testifies the importance of scientific communication in a plague. Our findings shed light on misinformation's distinct characteristics and its cultural, social, and political implications during the COVID-19. The study offers insights into combating misinformation in China and across the world. IEEE
ABSTRACT
Objective: To construct and evaluate a diagnosis pathway (Xiangya pathway) for Corona Virus Disease 2019 (COVID-19). Methods: Consecutive subjects aged ≥12 years old who were screened for COVID-19 were included in Xiangya Hospital of Central South University from January 23 to February 3, 2020, and the subjects were further divided into the inception cohort and the validation cohort. The gender, age, onset time of disease of the subjects were recorded. The information of epidemiological history, fever, and the declined blood lymphocytes were collected as clinical indicators, CT scan was used to evaluate the possibility of COVID-19 and range of lung involvement. According to the current Chinese national standards, throat swabs of suspected cases were collected and the nucleic acid of COVID-19 was detected by reverse transcription-polymerase chain reaction (RT-PCR). The Xiangya pathway was constructed with multi-indexes, compared with clinical indicators, CT results and Chinese national standards, their effectiveness of detecting confirmed cases were verified in the inception and validation cohort. Results: A total of 382 consecutive adults who was screened for COVID-19 were included, and 261 cases were in the inception cohort and 121 cases were in the validation cohort. Among the 382 cases, 192 were males (50.3%) and 190 were females (49.7%), with a median age of 35 years (range: 15-92 years). There were 183 cases (47.9%) with epidemiological history, 275 cases (72.0%) with fever, 212 cases (55.5%) with decreased peripheral blood lymphocytes, 114 cases (29.8%) with positive CT findings, 43 cases (11.3%) with positive CT-COVID-19, and 30 cases (7.9%) with positive virus nucleic acid by throat swab. Compared with clinical indicators, the sensitivity and specificity of CT were 0.950 and 0.704, respectively. The accuracy of CT to make a definite diagnosis was higher than that of epidemiological history, fever, and declined blood lymphocyte count (0.809 vs 0.660, 0.532, 0.596, P=0.001, 0.002, 0.003, respectively). The sensitivity of this pathway and the pathway recommended by the Health Commission of China were both high (all were 1.000), while the specificity and accuracy of the Xiangya pathway were higher than the one recommended by the Health Commission (0.872 vs 0.765, 0.778 vs 0.592, both P<0.001). The CT-COVID-19 reduced the missed diagnosis rate caused by false negative of nucleic acid test (31 vs 64), with difference rate of 51.6%, and the positive rate of nucleic acid test was 64.5% (20/31). In validation cohort, the specificity and accuracy of the Xiangya pathway was 0.967, the positive rate of nucleic acid test was 76.9%(10/13). Conclusions: The Xiangya pathway can predict the nucleic acid test results of COVID-19, and can be applied as a reliable strategy to screen patients with suspected COVID-19 among people aged ≥12 years in areas other than Hubei during the epidemic period of COVID-19. The cohort size needs to be increased for further validation.