Benchmarking variant callers in next-generation and third-generation sequencing analysis.

DNA variants represent an important source of genetic variations among individuals. Next- generation sequencing (NGS) is the most popular technology for genome-wide variant calling. Third-generation sequencing (TGS) has also recently been used in genetic studies. Although many variant callers are available, no single caller can call both types of variants on NGS or TGS data with high sensitivity and specificity. In this study, we systematically evaluated 11 variant callers on 12 NGS and TGS datasets. For germline variant calling, we tested DNAseq and DNAscope modes from Sentieon, HaplotypeCaller mode from GATK and WGS mode from DeepVariant. All the four callers had comparable performance on NGS data and 30× coverage of WGS data was recommended. For germline variant calling on TGS data, we tested DNAseq mode from Sentieon, HaplotypeCaller mode from GATK and PACBIO mode from DeepVariant. All the three callers had similar performance in SNP calling, while DeepVariant outperformed the others in InDel calling. TGS detected more variants than NGS, particularly in complex and repetitive regions. For somatic variant calling on NGS, we tested TNscope and TNseq modes from Sentieon, MuTect2 mode from GATK, NeuSomatic, VarScan2, and Strelka2. TNscope and Mutect2 outperformed the other callers. A higher proportion of tumor sample purity (from 10 to 20%) significantly increased the recall value of calling. Finally, computational costs of the callers were compared and Sentieon required the least computational cost. These results suggest that careful selection of a tool and parameters is needed for accurate SNP or InDel calling under different scenarios.

Inhibition of SARS-CoV-2 infection in human airway epithelium with a xeno-nucleic acid aptamer.

BACKGROUND: SARS-CoV-2, the agent responsible for the COVID-19 pandemic, enters cells through viral spike glycoprotein binding to the cellular receptor, angiotensin-converting enzyme 2 (ACE2). Given the lack of effective antivirals targeting SARS-CoV-2, we previously utilized systematic evolution of ligands by exponential enrichment (SELEX) and selected fluoro-arabino nucleic acid (FANA) aptamer R8-9 that was able to block the interaction between the viral receptor-binding domain and ACE2. METHODS: Here, we further assessed FANA-R8-9 as an entry inhibitor in contexts that recapitulate infection in vivo. RESULTS: We demonstrate that FANA-R8-9 inhibits spike-bearing pseudovirus particle uptake in cell lines. Then, using an in-vitro model of human airway epithelium (HAE) and SARS-CoV-2 virus, we show that FANA-R8-9 significantly reduces viral infection when added either at the time of inoculation, or several hours later. These results were specific to the R8-9 sequence, not the xeno-nucleic acid utilized to make the aptamer. Importantly, we also show that FANA-R8-9 is stable in HAE culture secretions and has no overt cytotoxic effects. CONCLUSIONS: Together, these results suggest that FANA-R8-9 effectively prevents infection by specific SARS-CoV-2 variants and indicate that aptamer technology could be utilized to target other clinically-relevant viruses in the respiratory mucosa.

FcRn-Targeted Mucosal Vaccination against Influenza Virus Infection.

The respiratory tract is constantly exposed to various airborne pathogens. Most vaccines against respiratory infections are designed for the parenteral routes of administration; consequently, they provide relatively minimal protection in the respiratory tract. A vaccination strategy that aims to induce the protective mucosal immune responses in the airway is urgently needed. The FcRn mediates IgG Ab transport across the epithelial cells lining the respiratory tract. By mimicking this natural IgG transfer, we tested whether FcRn delivers vaccine Ags to induce a protective immunity to respiratory infections. In this study, we designed a monomeric IgG Fc fused to influenza virus hemagglutinin (HA) Ag with a trimerization domain. The soluble trimeric HA-Fc were characterized by their binding with conformation-dependent HA Abs or FcRn. In wild-type, but not FcRn knockout, mice, intranasal immunization with HA-Fc plus CpG adjuvant conferred significant protection against lethal intranasal challenge with influenza A/PR/8/34 virus. Further, mice immunized with a mutant HA-Fc lacking FcRn binding sites or HA alone succumbed to lethal infection. Protection was attributed to high levels of neutralizing Abs, robust and long-lasting B and T cell responses, the presence of lung-resident memory T cells and bone marrow plasma cells, and a remarkable reduction of virus-induced lung inflammation. Our results demonstrate for the first time, to our knowledge, that FcRn can effectively deliver a trimeric viral vaccine Ag in the respiratory tract and elicit potent protection against respiratory infection. This study further supports a view that FcRn-mediated mucosal immunization is a platform for vaccine delivery against common respiratory pathogens.

Precision medicine integrating whole-genome sequencing, comprehensive metabolomics, and advanced imaging.

Genome sequencing has established clinical utility for rare disease diagnosis. While increasing numbers of individuals have undergone elective genome sequencing, a comprehensive study surveying genome-wide disease-associated genes in adults with deep phenotyping has not been reported. Here we report the results of a 3-y precision medicine study with a goal to integrate whole-genome sequencing with deep phenotyping. A cohort of 1,190 adult participants (402 female [33.8%]; mean age, 54 y [range 20 to 89+]; 70.6% European) had whole-genome sequencing, and were deeply phenotyped using metabolomics, advanced imaging, and clinical laboratory tests in addition to family/medical history. Of 1,190 adults, 206 (17.3%) had at least 1 genetic variant with pathogenic (P) or likely pathogenic (LP) assessment that suggests a predisposition of genetic risk. A multidisciplinary clinical team reviewed all reportable findings for the assessment of genotype and phenotype associations, and 137 (11.5%) had genotype and phenotype associations. A high percentage of genotype and phenotype associations (>75%) was observed for dyslipidemia (n = 24), cardiomyopathy, arrhythmia, and other cardiac diseases (n = 42), and diabetes and endocrine diseases (n = 17). A lack of genotype and phenotype associations, a potential burden for patient care, was observed in 69 (5.8%) individuals with P/LP variants. Genomics and metabolomics associations identified 61 (5.1%) heterozygotes with phenotype manifestations affecting serum metabolite levels in amino acid, lipid and cofactor, and vitamin pathways. Our descriptive analysis provides results on the integration of whole-genome sequencing and deep phenotyping for clinical assessments in adults.

Analysis of serum metabolism in premature infants before and after feeding using GC-MS and the relationship with necrotizing enterocolitis.

Preterm birth and enteral feeding are two main factors leading to necrotizing enterocolitis (NEC). The metabolomics of preterm infants before and after feeding can provide a basis for the prediction of NEC. Using the method of cross-sectional study, the mode was established with the serum samples of 19 premature infants at birth and after feeding as the control group. The serum was analyzed using GC-MS. Chemometric analysis includes principal component analysis, partial least squares-discriminant analysis, and orthogonal partial least squares-discriminant analysis. Spectral separation of serum metabolites occurred in premature infants before and after feeding. The levels of xylose, d-talose, phosphoglycolic acid, maleimide, l-gulonolactone, maleic acid, ß-hydroxypyruvate, itaconic acid, and pantothenic acid in the serum of premature infants after feeding were significant in both multidimensional and single-dimensional modes (variable importance in projection >2, P < 0.01). There was a moderate correlation between total bilirubin and l-gulonolactone and ß-hydroxypyruvate (0.8 > r > 0.5). Maleimide, maleic acid, and itaconic acid have diagnostic value (area under the curve >0.9). The results indicated that serum metabolism of preterm infants changes significantly after feeding. Some metabolites have potential value in predicting NEC.

Antibiotics at birth and later antibiotic courses: effects on gut microbiota.

BACKGROUND: Intrapartum antibiotic prophylaxis (IAP) is widely used, but the evidence of the long-term effects on the gut microbiota and subsequent health of children is limited. Here, we compared the impacts of perinatal antibiotic exposure and later courses of antibiotic courses on gut microbiota. METHODS: This was a prospective, controlled cohort study among 100 vaginally delivered infants with different perinatal antibiotic exposures: control (27), IAP (27), postnatal antibiotics (24), and IAP and postnatal antibiotics (22). At 1 year of age, we performed next-generation sequencing of the bacterial 16S ribosomal RNA gene of fecal samples. RESULTS: Exposure to the perinatal antibiotics had a clear impact on the gut microbiota. The abundance of the Bacteroidetes phylum was significantly higher in the control group, whereas the relative abundance of Escherichia coli was significantly lower in the control group. The impact of the perinatal antibiotics on the gut microbiota composition was greater than exposure to later courses of antibiotics (28% of participants). CONCLUSIONS: Perinatal antibiotic exposure had a marked impact on the gut microbiota at the age of 1 year. The timing of the antibiotic exposure appears to be the critical factor for the changes observed in the gut microbiota. IMPACT: Infants are commonly exposed to IAP and postnatal antibiotics, and later to courses of antibiotics during the first year of life. Perinatal antibiotics have been associated with an altered gut microbiota during the first months of life, whereas the evidence regarding the long-term impact is more limited. Perinatal antibiotic exposure had a marked impact on the infant's gut microbiota at 1 year of age. Impact of the perinatal antibiotics on the gut microbiota composition was greater than that of the later courses of antibiotics at the age of 1 year.

Vertical Transmission of Gut Microbiome and Antimicrobial Resistance Genes in Infants Exposed to Antibiotics at Birth.

Vertical transmission of maternal microbes is a major route for establishing the gut microbiome in newborns. The impact of perinatal antibiotics on vertical transmission of microbes and antimicrobial resistance is not well understood. Using a metagenomic approach, we analyzed the fecal samples from mothers and vaginally delivered infants from a control group (10 pairs) and a treatment group (10 pairs) receiving perinatal antibiotics. Antibiotic-usage had a significant impact on the main source of inoculum in the gut microbiome of newborns. The control group had significantly more species transmitted from mothers to infants (P = .03) than the antibiotic-treated group. Approximately 72% of the gut microbial population of infants at 3-7 days after birth in the control group was transmitted from their mothers, versus only 25% in the antibiotic-treated group. In conclusion, perinatal antibiotics markedly disturbed vertical transmission and changed the source of gut colonization towards horizontal transfer from the environment to the infants.

Clinical treatment outcomes and their changes in extremely preterm twins: a multicenter retrospective study in Guangdong Province, China. / è¶ æœªæˆç†ŸåŒèƒŽå„¿ä¸´åºŠæ•‘æ²»ç»“å±€åŠå˜åŒ–åˆ†æžï¼šä¸€é¡¹å¹¿ä¸œçœå¤šä¸­å¿ƒå›žé¡¾æ€§ç ”ç©¶.

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS: There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.

Deep learning-based six-type classifier for lung cancer and mimics from histopathological whole slide images: a retrospective study.

BACKGROUND: Targeted therapy and immunotherapy put forward higher demands for accurate lung cancer classification, as well as benign versus malignant disease discrimination. Digital whole slide images (WSIs) witnessed the transition from traditional histopathology to computational approaches, arousing a hype of deep learning methods for histopathological analysis. We aimed at exploring the potential of deep learning models in the identification of lung cancer subtypes and cancer mimics from WSIs. METHODS: We initially obtained 741 WSIs from the First Affiliated Hospital of Sun Yat-sen University (SYSUFH) for the deep learning model development, optimization, and verification. Additional 318 WSIs from SYSUFH, 212 from Shenzhen People's Hospital, and 422 from The Cancer Genome Atlas were further collected for multi-centre verification. EfficientNet-B5- and ResNet-50-based deep learning methods were developed and compared using the metrics of recall, precision, F1-score, and areas under the curve (AUCs). A threshold-based tumour-first aggregation approach was proposed and implemented for the label inferencing of WSIs with complex tissue components. Four pathologists of different levels from SYSUFH reviewed all the testing slides blindly, and the diagnosing results were used for quantitative comparisons with the best performing deep learning model. RESULTS: We developed the first deep learning-based six-type classifier for histopathological WSI classification of lung adenocarcinoma, lung squamous cell carcinoma, small cell lung carcinoma, pulmonary tuberculosis, organizing pneumonia, and normal lung. The EfficientNet-B5-based model outperformed ResNet-50 and was selected as the backbone in the classifier. Tested on 1067 slides from four cohorts of different medical centres, AUCs of 0.970, 0.918, 0.963, and 0.978 were achieved, respectively. The classifier achieved high consistence to the ground truth and attending pathologists with high intraclass correlation coefficients over 0.873. CONCLUSIONS: Multi-cohort testing demonstrated our six-type classifier achieved consistent and comparable performance to experienced pathologists and gained advantages over other existing computational methods. The visualization of prediction heatmap improved the model interpretability intuitively. The classifier with the threshold-based tumour-first label inferencing method exhibited excellent accuracy and feasibility in classifying lung cancers and confused nonneoplastic tissues, indicating that deep learning can resolve complex multi-class tissue classification that conforms to real-world histopathological scenarios.

Computational resources associating diseases with genotypes, phenotypes and exposures.

The causes of a disease and its therapies are not only related to genotypes, but also associated with other factors, including phenotypes, environmental exposures, drugs and chemical molecules. Distinguishing disease-related factors from many neutral factors is critical as well as difficult. Over the past two decades, bioinformaticians have developed many computational resources to integrate the omics data and discover associations among these factors. However, researchers and clinicians are experiencing difficulties in choosing appropriate resources from hundreds of relevant databases and software tools. Here, in order to assist the researchers and clinicians, we systematically review the public computational resources of human diseases related to genotypes, phenotypes, environment factors, drugs and chemical exposures. We briefly describe the development history of these computational resources, followed by the details of the relevant databases and software tools. We finally conclude with a discussion of current challenges and future opportunities as well as prospects on this topic.

100 Gbit/s co-designed optical receiver with hybrid integration.

We demonstrate a co-designed optical receiver, which is hybrid-integrated with a silicon-photonic photodetector (PD) and silicon-germanium (SiGe) trans-impedance amplifier (TIA). Accurate equivalent circuit models of PD and electrical parasitic of chip-on-board (COB) assembly are built for co-simulation with TIA. Inductive peaking and equalizer (EQ) techniques are proposed in the design of TIA to extend the bandwidth of the optical receiver. The measured electrical 3-dB bandwidth of TIA and optical-to-electrical (O-E) 3-dB bandwidth of optical receiver are above 36.8 GHz and 36 GHz, respectively. For the optical receiver, clear eye diagrams up to a data rate of 80 Gbit/s are realized. The bit-error ratios (BER) for the NRZ signal with a different bit rate and received optical power are experimentally measured, and 100 Gbit/s NRZ operation is successfully achieved with a soft-decision forward error correction (SD-FEC) threshold.

Microbial Species that Initially Colonize the Human Gut at Birth or in Early Childhood Can Stay in Human Body for Lifetime.

In recent years, many studies have described the composition and function of the human microbiome at different body sites and suggested a role for the microbiome in various diseases and health conditions. Some studies, using longitudinal samples, have also suggested how the microbiome changes over time due to disease, diet, development, travel, and other environmental factors. However, to date, no study has demonstrated whether the microorganisms established at birth or in early childhood, either transmitted from parents or obtained from the environment, can stay in the human body until adult or senior age. To directly answer this question is difficult, because microbiome samples at childhood and at later adulthood for the same individual will need to be compared and the field is not old enough to have allowed for that type of sample collection. Here, using a metagenomic approach, we analyzed 1004 gut microbiome samples from senior adults (65 ± 7.8 years) from the TwinsUK cohort. Our data indicate that many species in the human gut acquired in early childhood can stay for a lifetime until senior ages. We identified the rare genomic variants (single nucleotide variation and indels) for 27 prevalent species with enough sequencing coverage for confident genomic variant identification. We found that for some species, twin pairs, including both monozygotic (MZ) and dizygotic (DZ) twins, share significantly more rare variants than unrelated subject pairs. But no significant difference is found between MZ and DZ twin pairs. These observations strongly suggest that these species acquired in early childhood remained in these persons until senior adulthood.

Oral Microbial Species and Virulence Factors Associated with Oral Squamous Cell Carcinoma.

The human microbiome has been the focus of numerous research efforts to elucidate the pathogenesis of human diseases including cancer. Oral cancer mortality is high when compared with other cancers, as diagnosis often occurs during late stages. Its prevalence has increased in the USA over the past decade and accounts for over 40,000 new cancer patients each year. Additionally, oral cancer pathogenesis is not fully understood and is likely multifactorial. To unravel the relationships that are associated with the oral microbiome and their virulence factors, we used 16S rDNA and metagenomic sequencing to characterize the microbial composition and functional content in oral squamous cell carcinoma (OSCC) tumor tissue, non-tumor tissue, and saliva from 18 OSCC patients. Results indicate a higher number of bacteria belonging to the Fusobacteria, Bacteroidetes, and Firmicutes phyla associated with tumor tissue when compared with all other sample types. Additionally, saliva metaproteomics revealed a significant increase of Prevotella in five OSCC subjects, while Corynebacterium was mostly associated with ten healthy subjects. Lastly, we determined that there are adhesion and virulence factors associated with Streptococcus gordonii as well as from known oral pathogens belonging to the Fusobacterium genera found mostly in OSCC tissues. From these results, we propose that not only will the methods utilized in this study drastically improve OSCC diagnostics, but the organisms and specific virulence factors from the phyla detected in tumor tissue may be excellent biomarkers for characterizing disease progression.

High-speed lateral PIN germanium photodetector with 4-directional light input.

We experimentally demonstrate a high-speed lateral PIN junction configuration germanium photodetector (Ge-PD) with 4-directional light input. The typical internal responsivity is about 1.23 A/W at 1550 nm with 98% quantum efficiency and dark current 4 nA at 1V reverse-bias voltage. The equivalent circuit model and theoretical 3-dB opto-electrical (OE) bandwidth of Ge-PD are extracted and calculated, respectively. Compared to the conventional lateral PIN Ge-PD with 1-directional light input, our proposed device features uniform optical field distribution in the absorption region, which will be benefit to realize high-power and high-speed operation. In particular, in the condition of 0.8 mA photocurrent, the measured 3-dB OE bandwidth is about 17 GHz at bias voltage of -8 V which is well matched to the theoretical estimated bandwidth. With additional digital pre-compensations provided by the Keysight arbitrary waveform generator (AWG), the root raised cosine (RRC) filter and roll-off factor of 0.65 are employed at transmitter (TX) side without utilizing any offline digital signal processing (DSP) at receiver (RX) side. The 50 Gbit/s, 60 Gbit/s, 70 Gbit/s, and 80 Gbit/s non-return-to-zero (NRZ), and 60 Gbit/s, 70 Gbit/s, 80 Gbit/s, and 90 Gbit/s four-level pulse amplitude modulation (PAM-4) clear opening of eye diagrams are realized. In order to verify the high-power handling performance in high-speed data transmission, we also investigate the 20 Gbit/s NRZ eye diagram variations with the increasing of photocurrent.

ncRPheno: a comprehensive database platform for identification and validation of disease related noncoding RNAs.

Noncoding RNAs (ncRNAs) play critical roles in many critical biological processes and have become a novel class of potential targets and bio-markers for disease diagnosis, therapy, and prognosis. Annotating and analysing ncRNA-disease association data are essential but challenging. Current computational resources lack comprehensive database platforms to consistently interpret and prioritize ncRNA-disease association data for biomedical investigation and application. Here, we present the ncRPheno database platform (http://lilab2.sysu.edu.cn/ncrpheno), which comprehensively integrates and annotates ncRNA-disease association data and provides novel searches, visualizations, and utilities for association identification and validation. ncRPheno contains 482,751 non-redundant associations between 14,494 ncRNAs and 3,210 disease phenotypes across 11 species with supporting evidence in the literature. A scoring model was refined to prioritize the associations based on evidential metrics. Moreover, ncRPheno provides user-friendly web interfaces, novel visualizations, and programmatic access to enable easy exploration, analysis, and utilization of the association data. A case study through ncRPheno demonstrated a comprehensive landscape of ncRNAs dysregulation associated with 22 cancers and uncovered 821 cancer-associated common ncRNAs. As a unique database platform, ncRPheno outperforms the existing similar databases in terms of data coverage and utilities, and it will assist studies in encoding ncRNAs associated with phenotypes ranging from genetic disorders to complex diseases. ABBREVIATIONS: APIs: application programming interfaces; circRNA: circular RNA; ECO: Evidence & Conclusion Ontology; EFO: Experimental Factor Ontology; FDR: false discovery rate; GO: Gene Ontology; GWAS: genome wide association studies; HPO: Human Phenotype Ontology; ICGC: International Cancer Genome Consortium; lncRNA: long noncoding RNA; miRNA: micro RNA; ncRNA: noncoding RNA; NGS: next generation sequencing; OMIM: Online Mendelian Inheritance in Man; piRNA: piwi-interacting RNA; snoRNA: small nucleolar RNA; TCGA: The Cancer Genome Atlas.

Intestinal tract and parenteral multi-organ sequential pathological injury caused by necrotizing enterocolitis.

BACKGROUND: To explore the relationship between the pathological changes of the colon, terminal ileum, lung, liver and kidney, and the changes of Bax, PCNA and PAF in a rat model of NEC. METHODS: One hundred and forty neonatal SD rats were randomly divided into NEC group and control group (70 in each group). NEC group was given hypoxia, cold stimulation and artificial feeding twice a day for 3 consecutive days. The control group was only fed normally. After modeling, From the 1st day to the 7th day, 10 rats were sampled in each group for pathological examination of colon, terminal ileum, lung, liver and kidney tissue. The levels of Bax, PCNA and PAF were investigated by immunohistochemistry. RESULTS: Compared with the normal group, in the NEC group, on the 1st day, the colon, terminal ileum, lung, liver and kidney showed inflammatory damage. On the 5th day, the inflammatory injury was reduced. The inflammation disappeared on the 7th day. There were differences in the time of apoptosis in the intestine. In the intestine, the proliferation of PCNA was weak at first and then strong. Bax in liver and kidney showed marked apoptosis and apoptosis time increased in the lung. The expression of PCNA increased in lung, liver and kidney, and the expression of PAF increased in lung and liver. CONCLUSIONS: NEC can lead to secondary injury of different degrees in colon, terminal ileum, lung, liver and kidney, and the degree and time of injury and repair were different. In general, organ repair played a leading role on the 4th day after modeling.

Antimicrobial peptides: Promising alternatives in the post feeding antibiotic era.

Antimicrobial peptides (AMPs), critical components of the innate immune system, are widely distributed throughout the animal and plant kingdoms. They can protect against a broad array of infection-causing agents, such as bacteria, fungi, parasites, viruses, and tumor cells, and also exhibit immunomodulatory activity. AMPs exert antimicrobial activities primarily through mechanisms involving membrane disruption, so they have a lower likelihood of inducing drug resistance. Extensive studies on the structure-activity relationship have revealed that net charge, hydrophobicity, and amphipathicity are the most important physicochemical and structural determinants endowing AMPs with antimicrobial potency and cell selectivity. This review summarizes the recent advances in AMPs development with respect to characteristics, structure-activity relationships, functions, antimicrobial mechanisms, expression regulation, and applications in food, medicine, and animals.

32-GS/s 6-bit DAC based on SiGe technology for IM-DD OFDM systems with non-uniform quantization.

In this paper, we design and fabricate a 32-GS/s 6-bit digital-to-analog convertor (DAC) based on SiGe technology. The DAC uses double sampling technique and segment current steering architecture to achieve high dynamic linearity. A corrector circuit is proposed to suppress the duty cycle error for linearity optimization. The spurious free dynamic range (SFDR) is above 31.5 dBc over the Nyquist bandwidth at the sampling rate of 32-GS/s. A full-rate input interface is integrated to realize data exchange with field-programmable gate array (FPGA). The experimental results show that the net data rate of 50-Gb/s orthogonal frequency division multiplexing (OFDM) signals with non-uniform quantization can be generated by the designed and fabricated DAC. The OFDM signal transmission over 10-km standard single mode fiber (SSMF) with 64-quadrature amplitude modulation (QAM) and 128-QAM formats have been successfully achieved.

Query-seeded iterative sequence similarity searching improves selectivity 5-20-fold.

Iterative similarity search programs, like psiblast, jackhmmer, and psisearch, are much more sensitive than pairwise similarity search methods like blast and ssearch because they build a position specific scoring model (a PSSM or HMM) that captures the pattern of sequence conservation characteristic to a protein family. But models are subject to contamination; once an unrelated sequence has been added to the model, homologs of the unrelated sequence will also produce high scores, and the model can diverge from the original protein family. Examination of alignment errors during psiblast PSSM contamination suggested a simple strategy for dramatically reducing PSSM contamination. psiblast PSSMs are built from the query-based multiple sequence alignment (MSA) implied by the pairwise alignments between the query model (PSSM, HMM) and the subject sequences in the library. When the original query sequence residues are inserted into gapped positions in the aligned subject sequence, the resulting PSSM rarely produces alignment over-extensions or alignments to unrelated sequences. This simple step, which tends to anchor the PSSM to the original query sequence and slightly increase target percent identity, can reduce the frequency of false-positive alignments more than 20-fold compared with psiblast and jackhmmer, with little loss in search sensitivity.

Short-term outcomes of extremely preterm infants at discharge: a multicenter study from Guangdong province during 2008-2017.

BACKGROUND: An increasing number of extremely preterm (EP) infants have survived worldwide. However, few data have been reported from China. This study was designed to investigate the short-term outcomes of EP infants at discharge in Guangdong province. METHODS: A total of 2051 EP infants discharged from 26 neonatal intensive care units during 2008-2017 were enrolled. The data from 2008 to 2012 were collected retrospectively, and from 2013 to 2017 were collected prospectively. Their hospitalization records were reviewed. RESULTS: During 2008-2017, the mean gestational age (GA) was 26.68 ± 1.00 weeks and the mean birth weight (BW) was 935 ± 179 g. The overall survival rate at discharge was 52.5%. There were 321 infants (15.7%) died despite active treatment, and 654 infants (31.9%) died after medical care withdrawal. The survival rates increased with advancing GA and BW (p < 0.001). The annual survival rate improved from 36.2% in 2008 to 59.3% in 2017 (p < 0.001). EP infants discharged from hospitals in Guangzhou and Shenzhen cities had a higher survival rate than in others (p < 0.001). The survival rate of EP infants discharged from general hospitals was lower than in specialist hospitals (p < 0.001). The major complications were neonatal respiratory distress syndrome, 88.0% (1804 of 2051), bronchopulmonary dysplasia, 32.3% (374 of 1158), retinopathy of prematurity (any grade), 45.1% (504 of 1117), necrotizing enterocolitis (any stage), 10.1% (160 of 1588), intraventricular hemorrhages (any grade), 37.4% (535 of 1431), and blood culture-positive nosocomial sepsis, 15.7% (250 of 1588). The multivariate logistic regression analysis indicated that improved survival of EP infants was associated with discharged from specialist hospitals, hospitals located in high-level economic development region, increasing gestational age, increasing birth weight, antenatal steroids use and a history of premature rupture of membranes. However, twins or multiple births, Apgar ≤7 at 5 min, cervical incompetence, and decision to withdraw care were associated with decreased survival. CONCLUSIONS: Our study revealed the short-term outcomes of EP infants at discharge in China. The overall survival rate was lower than the developed countries, and medical care withdrawal was a serious problem. Nonetheless, improvements in care and outcomes have been made annually.