Bio-inspired 0.35μm CMOS Time-to-Digital Converter with 29.3ps LSB

Time-to-digital converter (TDC) integrated circuit is introduced in this paper. It is based on chain of delay elements composing a regular scalable structure. The scheme is analogous to the sound direction sensitivity nerve system found in barn owl. The circuit occupies small silicon area, and its direct mapping from time to position-code makes conversion rates up to 500Msps possible. Specialty of the circuit is the structural and functional symmetry. Therefore the role of start and stop signals are interchangeable. In other words negative delay is acceptable: the circuit has no dead time problems. These are benefits of the biology model of the auditory scene representation in the bird's brain. The prototype chip is implemented in 0.35μm CMOS having less than 30ps single-shot resolution in the measurements.Hungarian National Research Foundation TS4085

Host transcriptional responses in nasal swabs identify potential SARS-CoV-2 infection in PCR negative patients

We analyzed RNA sequencing data from nasal swabs used for SARS-CoV-2 testing. 13% of 317 PCR-negative samples contained over 100 reads aligned to multiple regions of the SARS-CoV-2 genome. Differential gene expression analysis compares the host gene expression in potential false-negative (FN: PCR negative, sequencing positive) samples to subjects with multiple SARS-CoV-2 viral loads. The host transcriptional response in FN samples was distinct from true negative samples (PCR & sequencing negative) and similar to low viral load samples. Gene Ontology analysis shows viral load-dependent changes in gene expression are functionally distinct; 23 common pathways include responses to viral infections and associated immune responses. GO analysis reveals FN samples had a high overlap with high viral load samples. Deconvolution of RNA-seq data shows similar cell content across viral loads. Hence, transcriptome analysis of nasal swabs provides an additional level of identifying SARS-CoV-2 infection

Experience versus complication rate in third molar surgery

OBJECTIVES: The records of 1087 patients who underwent surgical removal of third molar teeth were prospectively examined to analyse the possible relationship between postoperative complications and the surgeon's experience parameter. METHOD AND MATERIALS: Seven surgeons (three specialists in surgical dentistry [specialists SD] and four oral and maxillofacial Senior House Officers [OMFS residents]) carried out the surgical procedures. For each patient, several variables were recorded including age, gender, radiographic position of extracted teeth, treating surgeon, duration of surgery and postoperative complications. RESULTS: Analysis of the data revealed some differences in the incidence of complications produced by the specialists SD and OMFS residents. The main statistically relevant differences were increase the incidences of trismus, nerve paraesthesia, alveolar osteitis and infection in the resident-treated group, while the specialist-treated group showed higher rates of post-operative bleeding. CONCLUSION: The higher rate of postoperative complications in the resident-treated group suggests that at least some of the complications might be related to surgical experience. Further work needs to compare specialists of training programmes with different years of experience, using large cross – sectional studies

Interventions for iatrogenic inferior alveolar and lingual nerve injury

BackgroundIatrogenic injury of the inferior alveolar or lingual nerveor both is a known complication of oral and maxillofacial surgery procedures.Injury to these two branches of the mandibular division of thetrigeminal nerve may result in altered sensation associatedwith theipsilateral lower lip or tongue or both and may include anaesthesia, paraesthesia, dysaesthesia, hyperalgesia, allodynia, hypoaesthesiaand hyperaesthesia. Injury to the lingual nerve may also affect taste perception on the affected side of the tongue. The vastmajority(approximately 90%) of these injuries are temporary in nature and resolve within eight weeks. However, if the injury persists beyond sixmonths it is deemed to be permanent. Surgical, medical and psychological techniques have been used as a treatment for such injuries,though at present there is no consensus on the preferred intervention, or the timing of the intervention.ObjectivesTo evaluate the effects of different interventions and timings of interventions to treat iatrogenic injury of the inferior alveolar or lingualnerves.Search methodsWe searched the following electronic databases: the Cochrane Oral Health Group’s Trial Register (to 9 October 2013), the CochraneCentral Register of Controlled Trials (CENTRAL) (The Cochrane Library2013, Issue 9), MEDLINE via OVID (1946 to 9 October2013) and EMBASE via OVID (1980 to 9 October 2013). No language restrictions were placed on the language or date of publicationwhen searching the electronic databases.Selection criteriaRandomised controlled trials (RCTs) involving interventions to treat patients with neurosensory defect of the inferior alveolar or lingualnerve or both as a sequela of iatrogenic injury.Data collection and analysisWe used the standard methodological procedures expected by TheCochrane Collaboration. We performed data extraction and assess-ment of the risk of bias independently and in duplicate. We contacted authors to clarify the inclusion criteria of the studies. Main resultsTwo studies assessed as at high risk of bias, reporting data from 26 analysed participants were included in this review. Theage range ofparticipants was from 17 to 55 years. Both trials investigated the effectiveness of low-level laser treatment compared to placebo lasertherapy on inferior alveolar sensory deficit as a result of iatrogenic injury.Patient-reported altered sensation was partially reportedin one study and fully reported in another. Following treatment with lasertherapy, there was some evidence of an improvement in the subjective assessment of neurosensory deficit in the lip and chin areascompared to placebo, though the estimates were imprecise: a difference in mean change in neurosensory deficit of the chin of 8.40 cm(95% confidence interval (CI) 3.67 to 13.13) and a difference in mean change in neurosensory deficit of the lip of 21.79 cm (95% CI5.29 to 38.29). The overall quality of the evidence for this outcome was very low; the outcome data were fully reported in one smallstudy of 13 patients, with differential drop-out in the control group, and patients suffered only partial loss of sensation. No studiesreported on the effects of the intervention on the remaining primary outcomes of pain, difficulty eating or speaking or taste. No studiesreported on quality of life or adverse events.The overall quality of the evidence was very low as a result of limitations in the conduct and reporting of the studies, indirectness ofthe evidence and the imprecision of the results.Authors’ conclusionsThere is clearly a need for randomised controlled clinical trials to investigate the effectiveness of surgical, medical and psychologicalinterventions for iatrogenic inferior alveolar and lingual nerve injuries. Primary outcomes of this research should include: patient-focused morbidity measures including altered sensation and pain, pain, quantitative sensory testing and the effects of delayed treatmentNational Institute for Health Research (NIHR), U

Clonal Hematopoiesis Before, During, and After Human Spaceflight.

Clonal hematopoiesis (CH) occurs when blood cells harboring an advantageous mutation propagate faster than others. These mutations confer a risk for hematological cancers and cardiovascular disease. Here, we analyze CH in blood samples from a pair of twin astronauts over 4 years in bulk and fractionated cell populations using a targeted CH panel, linked-read whole-genome sequencing, and deep RNA sequencing. We show CH with distinct mutational profiles and increasing allelic fraction that includes a high-risk, TET2 clone in one subject and two DNMT3A mutations on distinct alleles in the other twin. These astronauts exhibit CH almost two decades prior to the mean age at which it is typically detected and show larger shifts in clone size than age-matched controls or radiotherapy patients, based on a longitudinal cohort of 157 cancer patients. As such, longitudinal monitoring of CH may serve as an important metric for overall cancer and cardiovascular risk in astronauts

System-wide transcriptome damage and tissue identity loss in COVID-19 patients

The molecular mechanisms underlying the clinical manifestations of coronavirus disease 2019 (COVID-19), and what distinguishes them from common seasonal influenza virus and other lung injury states such as acute respiratory distress syndrome, remain poorly understood. To address these challenges, we combine transcriptional profiling of 646 clinical nasopharyngeal swabs and 39 patient autopsy tissues to define body-wide transcriptome changes in response to COVID-19. We then match these data with spatial protein and expression profiling across 357 tissue sections from 16 representative patient lung samples and identify tissue-compartment-specific damage wrought by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, evident as a function of varying viral loads during the clinical course of infection and tissue-type-specific expression states. Overall, our findings reveal a systemic disruption of canonical cellular and transcriptional pathways across all tissues, which can inform subsequent studies to combat the mortality of COVID-19 and to better understand the molecular dynamics of lethal SARS-CoV-2 and other respiratory infections., • Across all organs, fibroblast, and immune cell populations increase in COVID-19 patients • Organ-specific cell types and functional markers are lost in all COVID-19 tissue types • Lung compartment identity loss correlates with SARS-CoV-2 viral loads • COVID-19 uniquely disrupts co-occurrence cell type clusters (different from IAV/ARDS) , Park et al. report system-wide transcriptome damage and tissue identity loss wrought by SARS-CoV-2, influenza, and bacterial infection across multiple organs (heart, liver, lung, kidney, and lymph nodes) and provide a spatiotemporal landscape of COVID-19 in the lung

Role of miR-2392 in driving SARS-CoV-2 infection

MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation that have a major impact on many diseases and provide an exciting avenue toward antiviral therapeutics. From patient transcriptomic data, we determined that a circulating miRNA, miR-2392, is directly involved with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) machinery during host infection. Specifically, we show that miR-2392 is key in driving downstream suppression of mitochondrial gene expression, increasing inflammation, glycolysis, and hypoxia, as well as promoting many symptoms associated with coronavirus disease 2019 (COVID-19) infection. We demonstrate that miR-2392 is present in the blood and urine of patients positive for COVID-19 but is not present in patients negative for COVID-19. These findings indicate the potential for developing a minimally invasive COVID-19 detection method. Lastly, using in vitro human and in vivo hamster models, we design a miRNA-based antiviral therapeutic that targets miR-2392, significantly reduces SARS-CoV-2 viability in hamsters, and may potentially inhibit a COVID-19 disease state in humans

The SEQC2 epigenomics quality control (EpiQC) study

BACKGROUND: Cytosine modifications in DNA such as 5-methylcytosine (5mC) underlie a broad range of developmental processes, maintain cellular lineage specification, and can define or stratify types of cancer and other diseases. However, the wide variety of approaches available to interrogate these modifications has created a need for harmonized materials, methods, and rigorous benchmarking to improve genome-wide methylome sequencing applications in clinical and basic research. Here, we present a multi-platform assessment and cross-validated resource for epigenetics research from the FDA's Epigenomics Quality Control Group. RESULTS: Each sample is processed in multiple replicates by three whole-genome bisulfite sequencing (WGBS) protocols (TruSeq DNA methylation, Accel-NGS MethylSeq, and SPLAT), oxidative bisulfite sequencing (TrueMethyl), enzymatic deamination method (EMSeq), targeted methylation sequencing (Illumina Methyl Capture EPIC), single-molecule long-read nanopore sequencing from Oxford Nanopore Technologies, and 850k Illumina methylation arrays. After rigorous quality assessment and comparison to Illumina EPIC methylation microarrays and testing on a range of algorithms (Bismark, BitmapperBS, bwa-meth, and BitMapperBS), we find overall high concordance between assays, but also differences in efficiency of read mapping, CpG capture, coverage, and platform performance, and variable performance across 26 microarray normalization algorithms. CONCLUSIONS: The data provided herein can guide the use of these DNA reference materials in epigenomics research, as well as provide best practices for experimental design in future studies. By leveraging seven human cell lines that are designated as publicly available reference materials, these data can be used as a baseline to advance epigenomics research