Wenhao Zhou

Bio: Wenhao Zhou is an academic researcher from Boston Children's Hospital. The author has contributed to research in topics: Medicine & Exome sequencing. The author has an hindex of 33, co-authored 168 publications receiving 4815 citations. Previous affiliations of Wenhao Zhou include Chinese Ministry of Health & Center for Excellence in Education.

Clinical analysis of 10 neonates born to mothers with 2019-nCoV pneumonia

Abstract: Background The newly identified 2019-nCoV, which appears to have originated in Wuhan, the capital city of Hubei province in central China, is spreading rapidly nationwide. A number of cases of neonates born to mothers with 2019-nCoV pneumonia have been recorded. However, the clinical features of these cases have not been reported, and there is no sufficient evidence for the proper prevention and control of 2019-nCoV infections in neonates. Methods The clinical features and outcomes of 10 neonates (including 2 twins) born to 9 mothers with confirmed 2019-nCoV infection in 5 hospitals from January 20 to February 5, 2020 were retrospectively analyzed. Results Among these 9 pregnant women with confirmed 2019-nCoV infection, onset of clinical symptoms occurred before delivery in 4 cases, on the day of delivery in 2 cases, and after delivery in 3 cases. In most cases, fever and a cough were the first symptoms experienced, and 1 patient also had diarrhea. Of the newborns born to these mothers, 8 were male and 2 were female; 4 were full-term infants and 6 were born premature; 2 were small-for-gestational-age (SGA) infants and 1 was a large-for-gestational-age (LGA) infant; there were 8 singletons and 2 twins. Of the neonates, 6 had a Pediatric Critical Illness Score (PCIS) score of less than 90. Clinically, the first symptom in the neonates was shortness of breath (n=6), but other initial symptoms such as fever (n=2), thrombocytopenia accompanied by abnormal liver function (n=2), rapid heart rate (n=1), vomiting (n=1), and pneumothorax (n=1) were observed. Up to now, 5 neonates have been cured and discharged, 1 has died, and 4 neonates remain in hospital in a stable condition. Pharyngeal swab specimens were collected from 9 of the 10 neonates 1 to 9 days after birth for nucleic acid amplification tests for 2019-nCoV, all of which showed negative results. Conclusions Perinatal 2019-nCoV infection may have adverse effects on newborns, causing problems such as fetal distress, premature labor, respiratory distress, thrombocytopenia accompanied by abnormal liver function, and even death. However, vertical transmission of 2019-nCoV is yet to be confirmed.

Neonatal Early-Onset Infection With SARS-CoV-2 in 33 Neonates Born to Mothers With COVID-19 in Wuhan, China.

Abstract: This cohort study examines medical records of 33 neonates born to women with COVID-19 to provide information on maternal-child transmission and infant outcomes.

Chinese expert consensus on the perinatal and neonatal management for the prevention and control of the 2019 novel coronavirus infection (First edition)

Abstract: Since December 2019, there has been an outbreak of novel coronavirus (2019-nCoV) infection in China. Two cases of neonates with positive 2019-nCoV tests have been reported. Due to the immature immune system and the possibility of vertical transmission from mother to infant, neonates have become a high-risk group susceptible to 2019-nCoV, which emphasize a close cooperation from both perinatal and neonatal pediatrics. In neonatal intensive care unit (NICU), to prevent and control infection, there should be practical measures to ensure the optimal management of children potentially to be infected. According to the latest 2019-nCoV national management plan and the actual situation, the Chinese Neonatal 2019-nCoV expert working Group has put forward measures on the prevention and control of neonatal 2019-nCoV infection.

Autism-like behaviours and germline transmission in transgenic monkeys overexpressing MeCP2

Abstract: Methyl-CpG binding protein 2 (MeCP2) has crucial roles in transcriptional regulation and microRNA processing. Mutations in the MECP2 gene are found in 90% of patients with Rett syndrome, a severe developmental disorder with autistic phenotypes. Duplications of MECP2-containing genomic segments cause the MECP2 duplication syndrome, which shares core symptoms with autism spectrum disorders. Although Mecp2-null mice recapitulate most developmental and behavioural defects seen in patients with Rett syndrome, it has been difficult to identify autism-like behaviours in the mouse model of MeCP2 overexpression. Here we report that lentivirus-based transgenic cynomolgus monkeys (Macaca fascicularis) expressing human MeCP2 in the brain exhibit autism-like behaviours and show germline transmission of the transgene. Expression of the MECP2 transgene was confirmed by western blotting and immunostaining of brain tissues of transgenic monkeys. Genomic integration sites of the transgenes were characterized by a deep-sequencing-based method. As compared to wild-type monkeys, MECP2 transgenic monkeys exhibited a higher frequency of repetitive circular locomotion and increased stress responses, as measured by the threat-related anxiety and defensive test. The transgenic monkeys showed less interaction with wild-type monkeys within the same group, and also a reduced interaction time when paired with other transgenic monkeys in social interaction tests. The cognitive functions of the transgenic monkeys were largely normal in the Wisconsin general test apparatus, although some showed signs of stereotypic cognitive behaviours. Notably, we succeeded in generating five F1 offspring of MECP2 transgenic monkeys by intracytoplasmic sperm injection with sperm from one F0 transgenic monkey, showing germline transmission and Mendelian segregation of several MECP2 transgenes in the F1 progeny. Moreover, F1 transgenic monkeys also showed reduced social interactions when tested in pairs, as compared to wild-type monkeys of similar age. Together, these results indicate the feasibility and reliability of using genetically engineered non-human primates to study brain disorders.

SPAdes, a new genome assembly algorithm and its applications to single-cell sequencing ( 7th Annual SFAF Meeting, 2012)

Abstract: The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.

Regulation of microRNA biogenesis

Abstract: MicroRNAs (miRNAs) are small non-coding RNAs that function as guide molecules in RNA silencing. Targeting most protein-coding transcripts, miRNAs are involved in nearly all developmental and pathological processes in animals. The biogenesis of miRNAs is under tight temporal and spatial control, and their dysregulation is associated with many human diseases, particularly cancer. In animals, miRNAs are ∼22 nucleotides in length, and they are produced by two RNase III proteins--Drosha and Dicer. miRNA biogenesis is regulated at multiple levels, including at the level of miRNA transcription; its processing by Drosha and Dicer in the nucleus and cytoplasm, respectively; its modification by RNA editing, RNA methylation, uridylation and adenylation; Argonaute loading; and RNA decay. Non-canonical pathways for miRNA biogenesis, including those that are independent of Drosha or Dicer, are also emerging.

Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review.

Abstract: Importance The coronavirus disease 2019 (COVID-19) pandemic, due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide sudden and substantial increase in hospitalizations for pneumonia with multiorgan disease. This review discusses current evidence regarding the pathophysiology, transmission, diagnosis, and management of COVID-19. Observations SARS-CoV-2 is spread primarily via respiratory droplets during close face-to-face contact. Infection can be spread by asymptomatic, presymptomatic, and symptomatic carriers. The average time from exposure to symptom onset is 5 days, and 97.5% of people who develop symptoms do so within 11.5 days. The most common symptoms are fever, dry cough, and shortness of breath. Radiographic and laboratory abnormalities, such as lymphopenia and elevated lactate dehydrogenase, are common, but nonspecific. Diagnosis is made by detection of SARS-CoV-2 via reverse transcription polymerase chain reaction testing, although false-negative test results may occur in up to 20% to 67% of patients; however, this is dependent on the quality and timing of testing. Manifestations of COVID-19 include asymptomatic carriers and fulminant disease characterized by sepsis and acute respiratory failure. Approximately 5% of patients with COVID-19, and 20% of those hospitalized, experience severe symptoms necessitating intensive care. More than 75% of patients hospitalized with COVID-19 require supplemental oxygen. Treatment for individuals with COVID-19 includes best practices for supportive management of acute hypoxic respiratory failure. Emerging data indicate that dexamethasone therapy reduces 28-day mortality in patients requiring supplemental oxygen compared with usual care (21.6% vs 24.6%; age-adjusted rate ratio, 0.83 [95% CI, 0.74-0.92]) and that remdesivir improves time to recovery (hospital discharge or no supplemental oxygen requirement) from 15 to 11 days. In a randomized trial of 103 patients with COVID-19, convalescent plasma did not shorten time to recovery. Ongoing trials are testing antiviral therapies, immune modulators, and anticoagulants. The case-fatality rate for COVID-19 varies markedly by age, ranging from 0.3 deaths per 1000 cases among patients aged 5 to 17 years to 304.9 deaths per 1000 cases among patients aged 85 years or older in the US. Among patients hospitalized in the intensive care unit, the case fatality is up to 40%. At least 120 SARS-CoV-2 vaccines are under development. Until an effective vaccine is available, the primary methods to reduce spread are face masks, social distancing, and contact tracing. Monoclonal antibodies and hyperimmune globulin may provide additional preventive strategies. Conclusions and Relevance As of July 1, 2020, more than 10 million people worldwide had been infected with SARS-CoV-2. Many aspects of transmission, infection, and treatment remain unclear. Advances in prevention and effective management of COVID-19 will require basic and clinical investigation and public health and clinical interventions.

The somatic genomic landscape of glioblastoma

Abstract: We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer.

Cooling for newborns with hypoxic ischaemic encephalopathy.

Abstract: Background Newborn animal and human pilot studies suggest that mild hypothermia following peripartum hypoxia-ischaemia in newborn infants may reduce neurological sequelae, without adverse effects. Objectives To determine whether therapeutic hypothermia in encephalopathic asphyxiated newborn infants reduces mortality and long-term neurodevelopmental disability, without clinically important side effects. Search strategy The standard search strategy of the Neonatal Review Group as outlined in the Cochrane Library (Issue 2, 2003) was used. Randomised controlled trials evaluating therapeutic hypothermia in term newborns with hypoxic ischaemic encephalopathy were identified by searching the Oxford Database of Perinatal Trials, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library Issue Issue 2, 2003), MEDLINE (1966 to July 2003), previous reviews including cross-references, abstracts, conferences, symposia proceedings, expert informants and journal hand searching. Selection criteria Randomised controlled trials comparing the use of therapeutic hypothermia with normothermia in encephalopathic newborn infants with evidence of peripartum asphyxia and without recognisable major congenital anomalies were included. The primary outcome measure was death or long-term major neurodevelopmental disability. Other outcomes included adverse effects of cooling and 'early' indicators of neurodevelopmental outcome. Data collection and analysis Three reviewers independently selected, assessed the quality of and extracted data from the included studies. Authors were contacted for further information. Meta-analyses were performed using relative risk and risk difference for dichotomous data, and weighted mean difference for continuous data with 95% confidence intervals. Main results Two randomised controlled trials were included in this review, comprising 50 term infants with moderate/ severe encephalopathy and evidence of intrapartum asphyxia. There was no significant effect of therapeutic hypothermia on the combined outcome of death or major neurodevelopmental disability in survivors followed. No adverse effects of hypothermia on short term medical outcomes or on some 'early' indicators of neurodevelopmental outcome were detected. Reviewer's conclusions Although two small randomised controlled trials demonstrated neither evidence of benefit or harm, current evidence is inadequate to assess either safety or efficacy of therapeutic hypothermia in newborn infants with hypoxic ischaemic encephalopathy. Therapeutic hypothermia for encephalopathic asphyxiated newborn infants should be further evaluated in well designed randomised controlled trials.