Predicting valuable missense variants with AlphaMissense in a multiple pulmonary infection patient.

AlphaMissense is proficient in predicting the clinical classification of missense variants. we utilized AlphaMissense to find disease-relevant variants within a polymicrobial pulmonary infection case. Exome sequencing was performed in this patient, and AlphaMissense and Phenolyzer were combined to investigate disease-relevant variants screening from exome sequencing results.

Flavorubredoxin, a Candidate Trigger Related to Thrombotic Thrombocytopenic Purpura: Screening of the Complete Genome of a Salmonella enterica Serovar Typhimurium Isolate From an AIDS Case.

Thrombotic thrombocytopenic purpura (TTP) is one of the two classic thrombotic microangiopathy (TMA) diseases which could be induced by infections. To the best of our knowledge, this is the first report of an acquired immunodeficiency syndrome (AIDS) patient with acquired TTP induced by infection with Salmonella enterica serovar Typhimurium (hereafter, S. Typhimurium) isolate, S. Typhimurium_zhang, which was confirmed by serology and genetic taxonomy. The literature review identified 17 TMA-related genes encoding the candidate triggers, which were searched in the annotated genome sequence of S. Typhimurium_zhang. Anaerobic nitric oxide reductase flavorubredoxin (FlRd), encoded by norV which is related to another TMA, haemolytic uraemic syndrome (HUS), was found in S. Typhimurium_zhang. Basic local alignment search tool (BLAST) analysis revealed that norV and FlRd in S. Typhimurium_zhang, as well as eight S. Typhimurium type strains, have high identity with HUS-related Escherichia coli O157:H7 strain TW14359. Similar results were obtained from the BLAST analysis of 73 S. enterica isolates for congenital TTP which was also previously reported to be triggered by S. enterica. Phylogenetic analysis and amino acid sequence alignment revealed that FlRd was functional and highly conservative on 69 Enterobacteriaceae, including S. Typimurium_zhang and TW14359. In brief, we found norV in the genome of a S. Typhimurium clinical isolate that induced TTP in an AIDS patient. FlRd, the protein encoded by norV, probably triggered the TTP and was highly conservative, functional, and widespread in S. enterica and Enterobacteriaceae. More in vitro and in vivo studies are required to confirm our findings and determine the underlying mechanism.

Preliminary Assessment of Chinese Strategy in Controlling Reemergent Local Outbreak of COVID-19.

Reemergent local outbreaks of coronavirus disease 2019 (COVID-19) have occurred in China, yet few Chinese response strategies and its evaluation have been reported. This study presents a preliminary assessment of Chinese strategy in controlling reemergent local outbreaks of COVID-19. Time course of accumulative and daily new cases and time-varying reproductive numbers (Rt) of outbreak areas were presented. The asymptomatic rate, days required to control the outbreaks, seeding time (ST), and doubling time (DT) of areas with over 96 reemergent cases were calculated. National and local year-on-year growth rates of gross domestic product (GDP) were presented. Accumulative numbers of 30, 8, 11, 430, 15, 139, 1,067, 382, 42, and 94 confirmed reemergent COVID-19 cases were diagnosed in Hulun Buir, Shanghai, Tianjin, Kashgar, Qingdao, Dalian, Urumchi, Beijing, Jilin, and Harbin, respectively. Among them, maximum rate of asymptomatic infections was 81.9%. Time required to control the local outbreaks in the areas given above varied from 29 to 51 days. After activation of outbreak responses, the late-stage DTs of Kashgar, Urumchi, Beijing, and Dalian were apparently lengthened compared to the early-stage DTs. Although the year-on-year GDP growth rate of Urumchi was slightly affected, the GDP growth rate of Dalian, Beijing, Jilin, and Harbin kept rising during the reemergence. Moreover, the year-on-year GDP growth rate of Mainland China turned positive regardless of the reemergent local outbreaks. In general, the Chinese strategy to maintain the status of no or minimal transmission was effective in balancing the control of COVID-19 reemergent local outbreak and the recovery of economy.

Case Report: Proven Diagnosis of Culture-Negative Chronic Disseminated Candidiasis in a Patient Suffering From Hematological Malignancy: Combined Application of mNGS and CFW Staining.

Chronic disseminated candidiasis (CDC) is a severe complication with high morbidity and mortality in patients with hematological malignancies who have undergone chemotherapy. Blood or sterile liver biopsy cultures are negative due to recurrent empirical antifungal therapy. With the escalating resistance to azole-based antifungal drugs in infection by Candida species, pathogen identification is becoming increasingly important for determining definitive diagnosis and treatment strategy. In this case report, we present, for the first time, diagnostic confirmation of a culture-negative CDC case with Candida tropicalis infection using a combination of metagenomics next-generation sequencing and calcofluor white staining.

A novel educational tool helps teach intestinal absorption in physiology.

A novel educational tool helps teach intestinal absorption in physiology-We have designed an interesting educational tool to help sophomores learn intestinal absorption in physiology course. In the study group (2019), 51 sophomores from biomedical engineering were encouraged to learn the intestinal absorption knowledge through reading materials and group discussion. Then, using the form of flipped class, they stepped on the podium and simulated and explained the absorption processes with designed paper props as educational tool. In contrast, the control group (2018), 52 sophomores from the same specialty had taken the same professional courses before. The result of theoretical test showed the average score in the study group was higher than that in the control group. The questionnaire analysis showed the positive role of the education tool in their learning efficacy. To sum up, using our tool has achieved better teaching effects than the traditional lecture.

Confirmation of the Need for Reclassification of Neisseria mucosa and Neisseria sicca Using Average Nucleotide Identity Blast and Phylogenetic Analysis of Whole-Genome Sequencing: Hinted by Clinical Misclassification of a Neisseria mucosa Strain.

The taxonomy of the genus Neisseria remains confusing, particularly regarding Neisseria mucosa and Neisseria sicca. In 2012, ribosomal multi-locus sequence typing reclassified both as N. mucosa, but data concerning 17 N. sicca strains remain available in GenBank. The continuous progress of high-throughput sequencing has facilitated ready accessibility of whole-genome data, promoting vigorous development of average nucleotide identity (ANI) and high-resolution phylogenetic analysis. Here, we report that a Neisseria isolate, which caused native-valve endocarditis and multiple embolic brain infarcts in a patient with congenital heart disease, was misidentified as N. sicca by VITEK MS. This isolate was reclassified as N. mucosa by ANI blast (ANIb) and by phylogenetic analysis using whole-genome data yielded by the PacBio Sequel and Illumina NovaSeq PE150 platforms. The confusion evident in the GenBank and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) databases suggests that N. mucosa (n = 13) and N. sicca (n = 16) in GenBank should be reclassified using ANIb and high-resolution phylogenetic analysis. The whole-genome data of 30 strains (including the clinical isolate) were compared with the data of 27 type Neisseria strains (including one N. sicca and two N. mucosa type strains) as a genomic index. In total, 25 (8 originally identified as N. mucosa and 17 originally identified as N. sicca) and 7 (1 originally identified as N. sicca and 6 originally identified as N. mucosa) strains were reclassified into the N. mucosa and Neisseria subflava groups, respectively; 1 residual N. mucosa strain was reclassified as Neisseria meningitidis. In conclusion, a combination of ANIb and robust phylogenetic analysis reclassified strains originally identified as N. mucosa and N. sicca into (principally) the N. mucosa group and the N. subflava group. The misclassified N. sicca and N. mucosa strains in the GenBank and MALDI-TOF MS databases were supposed to be corrected. Updated genomic classification strategy for originally identified N. mucosa and N. sicca strains was recommended to be adopted in GenBank.

Online Clinical Consultation as a Utility Tool for Managing Medical Crisis During a Pandemic: Retrospective Analysis on the Characteristics of Online Clinical Consultations During the COVID-19 Pandemic.

Coronavirus disease 2019 (COVID-19) is a newly-identified infectious diseases that has rapidly spread throughout the world with rising fatalities with declaration by World Health Organization as the pandemic. Online consultations have been shown to alleviate the pandemic with our study aims to demonstrate whether online consultation can be a solution for acute health crisis. Retrospective analysis of the characteristics of online consultations through two primary care online-consultation platforms during COVID-19 pandemic was performed at the Third Affiliated Hospital of Sun Yat-Sen University, which led the assessment of COVID-19-symptoms patients in Guangzhou. The 3473 online consultations were divided into pre-pandemic and pandemic period groups with Chi-square test as statistical analysis method. The number of online consultations has increased with diagnosis of upper respiratory tract infection, psychological conditions, COVID-19-related investigations and interventions. The increased online consultations met the increased demand of the relevant clinical services and reduced the overwhelming hospital presentations, thus decreasing the potential COVID-19 spread inside the major tertiary hospital and sparing the resources for acute crisis management. The epidemiology and disease characteristics of online consultations during the pandemic have been demonstrated with identification of the enabling factors and potential barriers in improving online healthcare in China with online consultation model being a durable solution for pandemic in future.

Inflammasome activation involved in early inflammation reaction after liver transplantation.

Liver transplantation has emerged as a vital therapy for end-stage liver diseases. Acute -phase inflammation play an important role in liver graft injury.Recent studies have revealed that inflammasome are responsible for initiating inflammation in early stage of acute organ rejection in liver transplantation, however the underlying mechanism remains unclear. Here we explored to block inflammasome activation to see whether it can alleviate early inflammation reaction during rejection of allgrafts in a rat model and gain further insights into the mechanism of inhibiting inflammation in allografts. By using Ac-YVAD-CMK, a highly selective caspase-1 inhibitor, to inhibit inflammation reaction involved in allograft rejection in a rat model. Our results showed that the rejection activity index (RAI) of Ac-YVAD-CMK-treated allografts is significantly diminished in similar magnitude to that of isografts. Compared with isografts, the expression of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and IL-1ß in allograft group increased significantly with the development of rejection, exhibiting apparent correlation. Expression of IFN-γ mRNA in untreated allografts was maximal on day 3 while in Ac-YVAD-CMK-treated allografts and isografts, IFN-γ mRNA levels remained low over the duration of the time course. ELISA results revealed serum elevation of IL-1ß by day 7 after othotopic liver transplantation (OLT) in comparison with isografts. There were no statistically significant differences between isografts and Ac-YVAD-CMK-treated allografts. For the first time, our data reveal that inhibition of the inflammasome activation pathway attenuates inflammation reaction of hepatic transplant rejection.