Miracle-dz/UniFAR-FTUs huggingface dataset:
Exuberant elevation of IP-10, MCP-3 and IL-1ra during SARS-CoV-2 infection is associated with disease severity and fatal outcome

The outbreak of Coronavirus Disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, December 2019, and continuously poses a serious threat to public health. Our previous study has shown that cytokine storm occurred during SARS-CoV-2 infection, while the detailed role of cytokines in the disease severity and progression remained unclear due to the limited case number. In this study, we examined 48 cytokines in the plasma samples from 53 COVID-19 cases, among whom 34 were severe cases, and the others moderate. Results showed that 14 cytokines were significantly elevated upon admission in COVID-19 cases. Moreover, IP-10, MCP-3, and IL-1ra were significantly higher in severe cases, and highly associated with the PaO2/FaO2 and Murray score. Furthermore, the three cytokines were independent predictors for the progression of COVID-19, and the combination of IP-10, MCP-3 and IL-1ra showed the biggest area under the curve (AUC) of the receiver-operating characteristics (ROC) calculations. Serial detection of IP-10, MCP-3 and IL-1ra in 14 severe cases showed that the continuous high levels of these cytokines were associated with disease deterioration and fatal outcome. In conclusion, we report three cytokines that closely associated with disease severity and outcome of COVID-19. These findings add to our understanding of the immunopathologic mechanisms of SARS-CoV-2 infection, which suggested novel therapeutic targets and strategy.
COVID-19 early warning score: a multi-parameter screening tool to identify highly suspected patients

BACKGROUND Corona Virus Disease 2019 (COVID-19) is spreading worldwide. Effective screening for patients is important to limit the epidemic. However, some defects make the currently applied diagnosis methods are still not very ideal for early warning of patients. We aimed to develop a diagnostic model that allows for the quick screening of highly suspected patients using easy-to-get variables. METHODS A total of 1,311 patients receiving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleicacid detection were included, whom with a positive result were classified into COVID-19 group. Multivariate logistic regression analyses were performed to construct the diagnostic model. Receiver operating characteristic (ROC) curve analysis were used for model validation. RESULTS After analysis, signs of pneumonia on CT, history of close contact, fever, neutrophil-to-lymphocyte ratio (NLR), Tmax and sex were included in the diagnostic model. Age and meaningful respiratory symptoms were enrolled into COVID-19 early warning score (COVID-19 EWS). The areas under the ROC curve (AUROC) indicated that both of the diagnostic model (training dataset 0.956 [95%CI 0.935-0.977, P < 0.001]; validation dataset 0.960 [95%CI 0.919-1.0, P < 0.001] ) and COVID-19 EWS (training dataset 0.956 [95%CI 0.934-0.978, P < 0.001] ; validate dataset 0.966 [95%CI 0.929-1, P < 0.001]) had good discrimination capacity. In addition, we also obtained the cut-off values of disease severity predictors, such as CT score, CD8+ T cell count, CD4+ T cell count, and so on. CONCLUSIONS The new developed COVID-19 EWS was a considerable tool for early and relatively accurately warning of SARS-CoV-2 infected patients.
A mathematical model for estimating the age-specific transmissibility of a novel coronavirus

Background: A novel coronavirus named as "SARS-CoV-2" has spread widely in many countries since December 2019, especially in China. This study aimed to quantify the age-specific transmissibility by using a mathematical model. Methods: An age-specific susceptible - exposed - symptomatic - asymptomatic - recovered - seafood market (SEIARW) model was developed based on two suspected transmission routes (from market to person and person to person). The susceptible people from Wuhan City were divided into different age groups. We used the subscript i and j to represent age group 1 to 4 (1: <= 14 years; 2: 15-44 years; 3: 45-64 years; 4: >= 65 years) and 1 to 5 (1: <= 5 years; 2: 6-14 years; 3: 15-24 years; 4: 25-59 years; 4: >= 60 years), respectively. Data of reported COVID-19 cases were collected from one published literature from 26 November to 22 December, 2019 in Wuhan City, China. The age-specific transmissibility of the virus was estimated accordingly secondary attack rate (SAR). Results: The age-specific SEIARW model fitted with the reported data well by dividing the population into four age groups (χ2 = 4.99 × 10-6, P > 0.999), and five age groups (χ2 = 4.85 × 10-6, P > 0.999). Based on the four-age-group SEIARW model, the highest transmissibility occurred from age group 2 to 3 (SAR23 = 17.56 per 10 million persons), followed by from age group 3 to 2 (SAR32 = 10.17 per 10 million persons). The lowest transmissibility occurred from age group 1 to 2 (SAR12 = 0.002 per 10 million persons). Based on the five-age-group SEIARW model, the highest transmissibility occurred from age group 4 to 5 (SAR45 = 12.40 per 10 million persons), followed by from age group 5 to 4 (SAR54 = 6.61 per 10 million persons). The lowest transmissibility occurred from age group 3 to 4 (SAR34 = 0.0002 per 10 million persons). Conclusions: SARS-CoV-2 has high transmissibility among adults and elder people but low transmissibility among children and young people.
DNA breaks are key contributors to the cost of antibiotic resistance

Antibiotic resistance often causes a fitness cost, which can lead to decreasing prevalence of resistance upon reducing antibiotics usage. The causes of the costs of resistance are, however, poorly understood, impairing our ability to manipulate its fate. Here we show that DNA breaks explain 73% of the variation in the cost of resistance mutations common in pathogens. We find that RNase HI is a key determinant of these costs and a novel target for antimicrobials specific against resistant bacteria. Indeed, lack of RNase HI rapidly drives Escherichia coli resistant clones to extinction in polymorphic populations with high resistance levels. These results provide a novel framework for the development of new strategies to lower the alarming levels of resistance in the human microbiome. One Sentence Summary DNA breaks drive the cost of antibiotic resistance, revealing specific targets against resistant bacteria.
Clinical characteristics of 36 non-survivors with COVID-19 in Wuhan, China

Background Although the outbreak of Coronavirus disease 2019 (COVID-19) has caused over 2200 deaths in China, there was no study about death yet. We aimed to describe the clinical characteristics of non-survivors with COVID-19. Methods For this retrospective, single-center study, we included 36 non-survivors with COVID-19 in the Fifth Hospital of Wuhan. Cases were confirmed by real-time RT-PCR between Jan 21 and Feb 10, 2020 according to the recommended protocol. The epidemiological, demographic, clinical, laboratory, radiological and treatment data were collected and analyzed. Outcomes were followed up until Feb 14, 2020. This study was approved by the ethics commissions of the Fifth Hospital of Wuhan, with a waiver of informed consent due to a public health outbreak investigation. Results We included 36 patients who died from COVID-19. The mean age of the patients was 69.22 years (SD 9.64, range 50-90). 25(69.44%) patients were males, and 11 (30.56%) female. 26 (72.22%) patients had chronic diseases, mainly including hypertension, cardiovascular disease and diabetes. Patients had common clinical symptoms of fever (34 [94.44%] patients), cough (28 [77.78%] patients), shortness of breath (21 [58.33%] patients), and fatigue (17 [47.22%] patient). Chest computed tomographic scans showed that 31 (96.88%) patients had bilateral pneumonia. Lymphopenia occurred in 24 patients (70.59%), decreased albumin (30.18, [SD, 4.76]) in 25 patients (80.65%), elevated D-dimer (8.64 [IQR, 2.39-20]) in 27 patients (100%), and elevated lactate dehydrogenase (502.5 U/L [IQR, 410-629]) in 26 patients (100%). Nearly all of the patients have elevated CRP (106.3 mg/L [IQR, 60.83-225.3]), PCT (0.61 ng/ml [IQR, 0.16-2.10]) and IL-6 (100.6 pg/ml [IQR, 51.51-919.5]). Most patients received antiviral therapy and antibiotic therapy, and more than half of patients received glucocorticoid therapy (25 [69.44%]). All the patients had acute respiratory distress syndrome (ARDS). The median time from onset to ARDS was 11 days. One (2.78%) patient presented with acute renal injury. The median time from onset to death was 17 days. Interpretation Lots of patients died from COVID-19 till now. The median survival time of these non-survivors from onset to death was about 2 weeks. Most patients were older males with comorbidities. They finally progressed to ARDS. The median time from onset to ARDS was 11 days. Gradually decreased lymphocytes and increased inflammation biomarkers were common, and need to be monitored in the routine treatment.
SARS-CoV-2 transmission in cancer patients of a tertiary hospital in Wuhan

In December 2019, an outbreak of atypical pneumonia known as 2019 novel coronavirus disease (COVID-19) occurred in Wuhan, China. This new type of pneumonia is characterized by rapid human-to-human transmission. Among the different disease types, cancer patients are often recalled to the hospital for treatment and disease surveillance, and the majority of cancer treatments such as chemotherapy and radiotherapy are immunosuppressive. This prompts us to consider if cancer patients were at an elevated risk of SARS-CoV-2 infection. A total of 1,524 cancer patients who were managed at our tertiary cancer institution-Zhongnan hospital of Wuhan University were reviewed during the period of Dec 30, 2019 to Feb 17, 2020. It was found that cancer patients had an estimated 2-fold increased risk of COVID-19 than the general population. We identified twelve patients who were infected with SARS-CoV-2, with two recorded deaths (16.7%), albeit one patient passed away from a COVID-19 unrelated cause. Interestingly, only five of these patients were ongoing treatment at the time of contracting the virus, suggesting that hospital visitation was the likely factor contributing to the elevated incidence in cancer patients. Moreover, we also observed that the incidence of severe COVID-19 was not higher than in the general population. Consequently, for cancer patients who require treatment, proper isolation protocols must be in place to mitigate the risk of SARS-CoV-2 infection.
Real-time monitoring the transmission potential of COVID-19 in Singapore, March 2020

As of March 31, 2020 the ongoing COVID-19 epidemic that started in China in December 2019 is now generating local transmission around the world. The geographic heterogeneity and associated intervention strategies highlight the need to monitor in real time the transmission potential of COVID-19. Singapore provides a unique case example for monitoring transmission, as there have been multiple disease clusters, yet transmission remains relatively continued. Here we estimate the effective reproduction number, Rt, of COVID-19 in Singapore from the publicly available daily case series of imported and autochthonous cases by date of symptoms onset, after adjusting the local cases for reporting delays as of March 17, 2020. We also derive the reproduction number from the distribution of cluster sizes using a branching process analysis that accounts for truncation of case counts. The local incidence curve displays sub-exponential growth dynamics, with the reproduction number following a declining trend and reaching an estimate at 0.7 (95% CI: 0.3, 1.0) during the first transmission wave by February 14, 2020 while the overall R based on the cluster size distribution as of March 17, 2020 was estimated at 0.6 (95% CI: 0.4, 1.02). The overall mean reporting delay was estimated at 6.4 days (95% CI: 5.8, 6.9), but it was shorter among imported cases compared to local cases (mean 4.3 vs. 7.6 days, Wilcoxon test, p<0.001). The trajectory of the reproduction number in Singapore underscores the significant effects of successful containment efforts in Singapore, but it also suggests the need to sustain social distancing and active case finding efforts to stomp out all active chains of transmission.
Clinical and radiographic features of cardiac injury in patients with 2019 novel coronavirus pneumonia

Objective: To investigate the correlation between clinical characteristics and cardiac injury of COVID-2019 pneumonia. Methods: In this retrospective, single-center study, 41 consecutive corona virus disease 2019 (COVID-2019) patients (including 2 deaths) of COVID-2019 in Beijing Youan Hospital, China Jan 21 to Feb 03, 2020, were involved in this study. The high risk factors of cardiac injury in different COVID-2019 patients were analyzed. Computed tomographic (CT) imaging of epicardial adipose tissue (EAT) has been used to demonstrate the cardiac inflammation of COVID-2019. ResultsOf the 41 COVID-2019 patients, 2 (4.88%), 32 (78.05%), 4 (9.75%) and 3 (7.32%) patients were clinically diagnosed as light, mild, severe and critical cases, according to the 6th guidance issued by the National Health Commission of China. 10 (24.4%) patients had underlying complications, such as hypertension, CAD, type 2 diabetes mellites and tumor. The peak value of TnI in critical patients is 40-fold more than normal value. 2 patients in the critical group had the onset of atrial fibrillation, and the peak heart rates reached up to 160 bpm. CT scan showed low EAT density in severe and critical patients. Conclusion: Our results indicated that cardiac injury of COVID-2019 was rare in light and mild patients, while common in severe and critical patients. Therefore, the monitoring of the heart functions of COVID-2019 patients and applying potential interventions for those with abnormal cardiac injury related characteristics, is vital to prevent the fatality.
Epidemiological and clinical features of 291 cases with coronavirus disease 2019 in areas adjacent to Hubei, China: a double-center observational study

Abstract Background: The clinical outcomes of COVID-19 patients in Hubei and other areas are different. We aim to investigate the epidemiological and clinical characteristics of patient with COVID-19 in Hunan which is adjacent to Hubei. Methods: In this double-center, observational study, we recruited all consecutive patients with laboratory confirmed COVID-19 from January 23 to February 14, 2020 in two designated hospitals in Hunan province, China. Epidemiological and clinical data from patients' electronic medical records were collected and compared between mild, moderate and severe/critical group in detail. Clinical outcomes were followed up to February 20, 2020. Findings: 291 patients with COVID-19 were categorized into mild group (10.0%), moderate group (72.8%) and severe/critical group (17.2%). The median age of all patients was 46 years (49.8% were male). 86.6% patients had an indirect exposure history. The proportion of patients that had been to Wuhan in severe/critical group (48.0% vs 17.2%, p=0.006) and moderate group (43.4% vs 17.2%, p=0.007) were higher than mild group. Fever (68.7%), cough (60.5%), and fatigue (31.6%) were common symptoms especially for severe and critical patients. Typical lung imaging finding were bilateral and unilateral ground glass opacity or consolidation. Leukopenia, lymphopenia and eosinopenia occurred in 36.1%, 22.7% and 50.2% patients respectively. Increased fibrinogen was detected in 45 of 58 (77.6%) patients with available results. 29 of 44 (65.9%) or 22 of 40 (55.0%) patients were positive in Mycoplasma pneumonia or Chlamydia pneumonia antibody test respectively. Compared with mild or moderate group, severe/critical group had a relative higher level of neutrophil, Neutrophil-to-Lymphocyte Ratio, h-CRP, ESR, CK, CK-MB, LDH, D-dimer, and a lower level of lymphocyte, eosinophils, platelet, HDL and sodium (all p<0.01). Most patients received antiviral therapy and Chinese Medicine therapy. As of February 20, 2020, 159 (54.6%) patients were discharged and 2 (0.7%) patients died during hospitalization. The median length of hospital stay in discharged patients was 12 days (IQR: 10-15). Interpretation: The epidemiological and clinical characteristics of COVID-19 patients in Hunan is different from patients in Wuhan. The proportion of patients that had been to Wuhan in severe/critical group and moderate group were higher than mild group. Laboratory and imaging examination can assist in the diagnosis and classification of COVID-19 patients.
Community responses during the early phase of the COVID-19 epidemic in Hong Kong: risk perception, information exposure and preventive measures

Background: Community responses are important for outbreak management during the early phase when non-pharmaceutical interventions are the major preventive options. Therefore, this study aims to examine the psychological and behavioral responses of the community during the early phase of the COVID-19 epidemic in Hong Kong. Method: A cross-sectional online survey was launched within 36 hours after confirmed COVID-19 cases were first reported. Councilors of all 452 district council constituency areas were approached for survey dissemination. Respondent demographics, anxiety level, risk perception, sources to retrieve COVID-19 information, actual adoption and perceived efficacy of precautionary measures were collected. Result: Analysis from 1715 complete responses indicated high perceived susceptibility (89%) and high perceived severity (97%). Most respondents were worried about COVID-19 (97%), and had their daily routines disrupted (slightly/greatly: 98%). The anxiety level, measured by the Hospital Anxiety and Depression Scale, was borderline abnormal (9.01). Nearly all respondents were alert to the disease progression (99.5%). The most trusted information sources were doctors (84%), followed by broadcast (57%) and newspaper (54%), but they were not common information sources (doctor: 5%; broadcast: 34%; newspaper: 40%). Only 16% respondents found official websites reliable. Enhanced personal hygiene practices and travel avoidance to China were frequently adopted (>77%) and considered effective (>90%). The adoption of social-distancing measures was lower (39%-88%), and their drivers for greater adoption include: being female (adjusted odds ratio [aOR]:1.27), living in the New Territories (aOR:1.32-1.55), perceived as having good understanding of COVID-19 (aOR:1.84) and being more anxious (aOR:1.07). Discussion: Risk perception towards COVID-19 in the community was high. Most respondents are alert to the disease progression, and adopt self-protective measures. This study contributes by examining the psycho-behavioral responses of hosts, in addition to the largely studied mechanistic aspects, during the early phase of the current COVID-19 epidemic. The timely psychological and behavioral assessment of the community is useful to inform subsequent interventions and risk communication strategies as the epidemic progresses.
Early Prediction of Disease Progression in 2019 Novel Coronavirus Pneumonia Patients Outside Wuhan with CT and Clinical Characteristics

Objective: To determine the predictive value of CT and clinical characteristics for short-term disease progression in patients with 2019 novel coronavirus pneumonia (NCP). Materials and Methods: 224 patients with confirmed 2019 novel coronavirus (COVID-19) infection outside Wuhan who had chest CT examinations were retrospectively screened. Clinical data were obtained from electronic medical records. CT images were reviewed and scored for lesion distribution, lobe and segment involvement, ground-glass opacities, consolidation, and interstitial thickening. All included patients with moderate NCP were observed for at least 14 days from admission to determine whether they exacerbated to severe NCP (progressive group) or not (stable group). CT and clinical characteristics between the two groups were compared, and multivariate logistic regression and sensitivity analyses were performed to identify the risk factors for developing severe NCP. Results: A total of 141 patients with moderate NCP were included, of which 15 (10.6%) patients developed severe NCP during hospitalization and assigned to the progressive group. Multivariate logistic regression analysis showed that higher neutrophil-to-lymphocyte ratio (NLR) (odds ratio [OR] and 95% confidence interval [CI], 1.26 [1.04-1.53]; P = 0.018) and CT severity score (OR and 95% CI, 1.25 [1.08-1.46]; P = 0.004) on admission were independent predictors for progression to severe NCP, and sensitivity analysis confirmed the consistent results in nonimported patients but not in imported patients. However, no significant difference in lung involvement was found on CT between imported and nonimported patients (all P > 0.05). Patients who were admitted more than 4 days from symptom onset tended to have more severe lung involvement. Spearman correlation analysis showed the close association between CT severity score and inflammatory indexes (r = 0.17~0.47, all P < 0.05). Conclusion: CT severity score was associated with inflammatory levels and higher NLR and CT severity score on admission were independent risk factors for short-term progression in patients with NCP outside Wuhan. Furthermore, early admission and surveillance by CT should be recommended to improve clinical outcomes.
BRAF inhibitor PLX4720 in two BRAF inhibitor-resistant cells, indicating a positive role for Spry2 in the growth inhibition induced by BRAF inhibitors. On the other hand, long-term treatment with PLX4720 induced pERK reactivation following BRAF inhibition in A375P

Gain-of-function mutations in BRAF have been identifi ed in various cancers (Davies et al., 2002). Notably, BRAF somatic mutations have been observed in 66% of malignant melanomas (Davies et al., 2002), and these exhibit a valine-to-glutamate substitution (V600E), which renders BRAF constitutively active. This prevalence of BRAF mutations has prompted efforts to develop inhibitors of the mutated BRAF (Sabbatino et al., 2013; Holderfi eld et al., 2014). Selective BRAF inhibitors including vemurafenib and dabrafenib displayed potent antineoplastic activities in tumor cells bearing BRAF V600E, whereas lacking their activity in cell lines that express wildtype (WT) BRAF. It has been demonstrated clinical benefi ts in patients with BRAF V600E melanoma (Flaherty et al., 2010; McGettigan, 2014). We also recently reported UAI-201 (also described as UI-152) as a potent ATP-competitive inhibitor of RAF proteins (Kim et al., 2012). UAI-201 was more than 1,000-fold more selective in inhibiting the proliferation of tumor cell lines bearing the BRAF-V600E mutation compared with cells bearing wild-type BRAF (Kim et al., 2012). However, intrinsic and acquired resistance limits the therapeutic benefi ts of these oncogenic BRAF inhibitors (Flaherty et al., 2010; Rizos et al., 2014). The mechanisms that underlie the therapeutic resistance of melanoma include the overexpression of MAP kinase kinase kinase 8 (MAP3K8; COT) (Johannessen et al., 2010), mutations in N-Ras, and PDGFRβ overexpression (Nazarian et al., 2010). Our previous study also implicated the upregulation of N-Ras as a key mechanism of acquired resistance to oncogenic BRAF inhibitors Original Article Biomol Ther 23(4), 320-326 (2015)