MICA: A fast short-read aligner that takes full advantage of Many Integrated Core Architecture (MIC)

Background: Short-read aligners have recently gained a lot of speed by exploiting the massive parallelism of GPU. An uprising alterative to GPU is Intel MIC; supercomputers like Tianhe-2, currently top of TOP500, is built with 48,000 MIC boards to offer ~55 PFLOPS. The CPU-like architecture of MIC allows CPU-based software to be parallelized easily; however, the performance is often inferior to GPU counterparts as an MIC card contains only ~60 cores (while a GPU card typically has over a thousand cores). Results: To better utilize MIC-enabled computers for NGS data analysis, we developed a new short-read aligner MICA that is optimized in view of MIC's limitation and the extra parallelism inside each MIC core. By utilizing the 512-bit vector units in the MIC and implementing a new seeding strategy, experiments on aligning 150 bp paired-end reads show that MICA using one MIC card is 4.9 times faster than BWA-MEM (using 6 cores of a top-end CPU), and slightly faster than SOAP3-dp (using a GPU). Furthermore, MICA's simplicity allows very efficient scale-up when multiple MIC cards are used in a node (3 cards give a 14.1-fold speedup over BWA-MEM). Summary: MICA can be readily used by MIC-enabled supercomputers for production purpose. We have tested MICA on Tianhe-2 with 90 WGS samples (17.47 Tera-bases), which can be aligned in an hour using 400 nodes. MICA has impressive performance even though MIC is only in its initial stage of development. Availability and implementation: MICA's source code is freely available at http://sourceforge.net/projects/mica-aligner under GPL v3. Supplementary information: Supplementary information is available as "Additional File 1". Datasets are available at www.bio8.cs.hku.hk/dataset/mica.published_or_final_versio

Whole-genome sequencing of the snub-nosed monkey provides insights into folivory and evolutionary history

Colobines are a unique group of Old World monkeys that principally eat leaves and seeds rather than fruits and insects. We report the sequencing at 146× coverage, de novo assembly and analyses of the genome of a male golden snub-nosed monkey (Rhinopithecus roxellana) and resequencing at 30× coverage of three related species (Rhinopithecus bieti, Rhinopithecus brelichi and Rhinopithecus strykeri). Comparative analyses showed that Asian colobines have an enhanced ability to derive energy from fatty acids and to degrade xenobiotics. We found evidence for functional evolution in the colobine RNASE1 gene, encoding a key secretory RNase that digests the high concentrations of bacterial RNA derived from symbiotic microflora. Demographic reconstructions indicated that the profile of ancient effective population sizes for R. roxellana more closely resembles that of giant panda rather than its congeners. These findings offer new insights into the dietary adaptations and evolutionary history of colobine primates

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Correlation between LncRNA Profiles in the Blood Clot Formed on Nano-Scaled Implant Surfaces and Osseointegration

Implant surfaces with a nanoscaled pattern can dominate the blood coagulation process resulting in a defined clot structure and its degradation behavior, which in turn influence cellular response and the early phase of osseointegration. Long non-coding (Lnc) RNAs are known to regulate many biological processes in the skeletal system; however, the link between the LncRNA derived from the cells within the clot and osseointegration has not been investigated to date. Hence, the sequence analysis of LncRNAs expressed within the clot formed on titania nanotube arrays (TNAs) with distinct nano-scaled diameters (TNA 15 of 15 nm, TNA 60 of 60 nm, TNA 120 of 120 nm) on titanium surfaces was profiled for the first time. LncRNA LOC103346307, LOC103352121, LOC108175175, LOC103348180, LOC108176660, and LOC108176465 were identified as the pivotal players in the early formed clot on the nano-scaled surfaces. Further bioinformatic prediction results were used to generate co-expression networks of LncRNAs and mRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that distinct nano-scaled surfaces could regulate the biological functions of target mRNAs in the clot. LOC103346307, LOC108175175, and LOC108176660 upregulated mRNAs related to cell metabolism and Wnt, TGF-beta, and VEGF signaling pathways in TNA 15 compared with P-Ti, TNA 60, and TNA 120, respectively, whereas LOC103352121, LOC103348180, and LOC108176465 downregulated mRNAs related to bone resorption and inflammation through negatively regulating osteoclast differentiation, TNF, and NF-kappa signaling pathways. The results indicated that surface nano-scaled characteristics can significantly influence the clot-derived LncRNAs expression profile, which affects osseointegration through multiple signaling pathways of the targeted mRNAs, thus paving a way for better interpreting the link between the properties of a blood clot formed on the nano-surface and de novo bone formation

Understanding LncRNAs in Biomaterials Development for Osteointegration

Osseointegration of implants is a sophisticated healing process comprising of blood clot formation, immune response, angiogenesis, and osteogenesis. The features of the blood clots take a crucial role in fulfilling rapid and satisfying osseointegration. Nano-scaled implant surfaces can dominate the structure, thickness, and coagulation process of blood clots, thereby influencing inflammation and bone regeneration. Long non-coding RNAs (LncRNAs) are actively involved in regulating the transcription of protein-coding genes and have profound effects on a variety of biological processes. This chapter will provide a basic introduction of osseointegration processes and LncRNAs, and focus on the effects of LncRNA profiles within nano-scaled implant surface-mediated blood clots on osseointegration. The sequence analysis of LncRNAs manifests that different titania nanotube arrays (TNAs) can mediate the distinct clot-derived LncRNA expression profiles. Moreover, LncRNAs LOC103346307, LOC103352121, LOC108175175, LOC103348180, LOC108176660, and LOC108176465 are identified as the pivotal players in the early formed clots on the nano-scaled surfaces. Further bioinformatic prediction indicates that the key LncRNA profiles target the mRNAs related to cell growth and metabolism, bone resorption, and inflammation. The current knowledge demonstrates that in the early stage of osseointegration, surface nano-scaled characteristics of the implants can significantly influence the LncRNA expression in the blood clots, which affects the immune responses, angiogenesis, and osteogenesis through modulating the transcription of targeted mRNAs involved in multiple signaling pathways. The introduction of this chapter paves a way for better interpreting the link between the properties of a blood clot formed on the nano-surface and new bone formation and presents a reference for understanding LncRNAs in biomaterial development for osteointegration.</p

Engineered functional doped hydroxyapatite coating on titanium implants for osseointegration

Titanium (Ti) and its alloys are commonly used implant materials in orthopedics due to their good corrosion resistance, mechanical properties, and biocompatibility. However, the inherent biological inertness of the Ti surface leads to insufficient osseointegration and antibacterial ability, which may result in implant failure. Hydroxyapatite (HA) is currently the most widely used material in the biomedical field. It is one of the bioactive coating materials because of its chemical and structural similarity to natural bone. At present, many techniques are used to deposit HA as a coating material on Ti implants. The stability of the HA coating is the most important factor in determining the success of the implant. In addition, biofunctional ions have been introduced into HA coatings to enhance functional performance. This article aims to present the crystal structure and characteristics of HA and the principle of doping ions into HA. The preparation methods for the deposition of HA functional coatings on Ti and its alloys are introduced and discuss its advantages and limitations. In addition, the coating of doped HA on the surface of Ti and its alloys to improve their surface properties for bone integration is also reviewed

Biodegradable Metallic Wires in Dental and Orthopedic Applications: A Review

Owing to significant advantages of bioactivity and biodegradability, biodegradable metallic materials such as magnesium, iron, and zinc and their alloys have been widely studied over recent years. Metallic wires with superior tensile strength and proper ductility can be fabricated by a traditional metalworking process (drawing). Drawn biodegradable metallic wires are popular biodegradable materials, which are promising in different clinical applications such as orthopedic fixation, surgical staples, cardiovascular stents, and aneurysm occlusion. This paper presents recent advances associated with the application of biodegradable metallic wires used in dental and orthopedic fields. Furthermore, the effects of some parameters such as the surface modification, alloying elements, and fabrication process affecting the degradation rate as well as biocompatibility, bioactivity, and mechanical stability are reviewed in the most recent works pertaining to these materials. Finally, possible pathways for future studies regarding the production of more efficient biodegradable metallic wires in the regeneration of bone defects are also proposed

Biodegradable Metallic Wires in Dental and Orthopedic Applications: A Review

Owing to significant advantages of bioactivity and biodegradability, biodegradable metallic materials such as magnesium, iron, and zinc and their alloys have been widely studied over recent years. Metallic wires with superior tensile strength and proper ductility can be fabricated by a traditional metalworking process (drawing). Drawn biodegradable metallic wires are popular biodegradable materials, which are promising in different clinical applications such as orthopedic fixation, surgical staples, cardiovascular stents, and aneurysm occlusion. This paper presents recent advances associated with the application of biodegradable metallic wires used in dental and orthopedic fields. Furthermore, the effects of some parameters such as the surface modification, alloying elements, and fabrication process affecting the degradation rate as well as biocompatibility, bioactivity, and mechanical stability are reviewed in the most recent works pertaining to these materials. Finally, possible pathways for future studies regarding the production of more efficient biodegradable metallic wires in the regeneration of bone defects are also proposed

A micro/nano-biomimetic coating on titanium orchestrates osteo/angio-genesis and osteoimmunomodulation for advanced osseointegration

Osseointegration is a sophisticated bone and implant healing process comprising of initial hematoma formation, immediate osteoimmunomodulation, angiogenesis, and osteogenesis. To fulfill rapid and satisfying osseointegration, this study developed a biomimetic implant coating that could confer the intraosseous implants a systematical regulation of the participatory processes. Herein, we shaped dissimilar nano-scale (NS) to form highly biomimetic structures of natural extracellular matrix (ECM) of the host bone and bone healing hematoma with micro/nano-scale (MNS) titania fiber-like network on the surface of titanium (Ti) implants. In vitro experiments revealed that the MNS not only facilitated osteogenic and angiogenic differentiation of bone marrow stromal cells (BMSCs) and endothelial cells, respectively, but also suppressed M1 macrophages (MΦs), whereas, stimulated pro-healing M2 phenotype. Notably, BMSCs on MNS surfaces enabled a significant immunomodulatory effect on MΦs resulting in the downregulation of inflammation-related cell signaling pathways. The favorable osteoimmune microenvironment manipulated by MNS further facilitated osteo-/angio-genesis via the crosstalk of multi-signaling pathways. In vivo evaluation mirrored the aforementioned results, and depicted that MNS induced ameliorative osseointegration when compared with the NS as well as the pristine Ti implant. The study demonstrated the modulatory effect of the multifaceted biomimetic structure on spatiotemporal regulation of the participatory processes during osseointegration