Patterns of Unwanted Biological and Technical Expression Variation Among 49 Human Tissues.

Tissue gene expression studies are impacted by biological and technical sources of variation, which can be broadly classified into wanted and unwanted variation. The latter, if not addressed, results in misleading biological conclusions. Methods have been proposed to reduce unwanted variation, such as normalization and batch correction. A more accurate understanding of all causes of variation could significantly improve the ability of these methods to remove unwanted variation while retaining variation corresponding to the biological question of interest. We used 17,282 samples from 49 human tissues in the Genotype-Tissue Expression data set (v8) to investigate patterns and causes of expression variation. Transcript expression was transformed to z-scores, and only the most variable 2% of transcripts were evaluated and clustered based on coexpression patterns. Clustered gene sets were assigned to different biological or technical causes based on histologic appearances and metadata elements. We identified 522 variable transcript clusters (median: 11 per tissue) among the samples. Of these, 63% were confidently explained, 16% were likely explained, 7% were low confidence explanations, and 14% had no clear cause. Histologic analysis annotated 46 clusters. Other common causes of variability included sex, sequencing contamination, immunoglobulin diversity, and compositional tissue differences. Less common biological causes included death interval (Hardy score), disease status, and age. Technical causes included blood draw timing and harvesting differences. Many of the causes of variation in bulk tissue expression were identifiable in the Tabula Sapiens data set of single-cell expression. This is among the largest explorations of the underlying sources of tissue expression variation. It uncovered expected and unexpected causes of variable gene expression and demonstrated the utility of matched histologic specimens. It further demonstrated the value of acquiring meaningful tissue harvesting metadata elements to use for improved normalization, batch correction, and analysis of both bulk and single-cell RNA-seq data.

Brooklyn plots to identify co-expression dysregulation in single cell sequencing.

Altered open chromatin regions, impacting gene expression, is a feature of some human disorders. We discovered it is possible to detect global changes in genomically-related adjacent gene co-expression within single cell RNA sequencing (scRNA-seq) data. We built a software package to generate and test non-randomness using 'Brooklyn plots' to identify the percent of genes significantly co-expressed from the same chromosome in ∼10 MB intervals across the genome. These plots establish an expected low baseline of co-expression in scRNA-seq from most cell types, but, as seen in dilated cardiomyopathy cardiomyocytes, altered patterns of open chromatin appear. These may relate to larger regions of transcriptional bursting, observable in single cell, but not bulk datasets.

Enhanced O2/N2 separation by QuaternizedMatrimid/Multiwalled carbon nanotube mixed-matrix membrane.

The air separation (O2/N2) based on polymeric membranes is critical because it is more energy efficient than traditional methods. Dense polymeric membranes are now the main stay of industrial processes that generate oxygen and nitrogen enriched gas. Though, regular polymeric membranes often fall short of selective pressure demands because O2 and N2 gases have such comparable equivalent diameters. While polymer composites have their benefits, nanocomposite (NCs) allows for the production of high-performance barriers. Utilising Matrimid® 5218 (Matrimid) as the base framework and multiwall carbon nanotube (MWCNT) as the filler, a novel NCs for O2/N2 separation was developed. Both matrimid and MWCNTs were chemically modified quaternization and functionalizing the MWCNTs. The membranes were casted using solution casting with a combination of quaternized matrimid and functionalized multi-walled carbon nanotubes (f-MWCNT). When f-MWCNT was added to quaternized matrimid, it created interfacial compatibility, which increased O2/N2 selectivity and permeability by 65 % and 35 %, respectively. In the current study, increasing O2 diffusivity and O2/N2 solubility selectivity resulted in improved performance, this paves a way for manufacturing innovation.

An Experimental and Simulation Study of the Active Camber Morphing Concept on Airfoils Using Bio-Inspired Structures.

Birds are capable of morphing their wings across different flight modes and speeds to improve their aerodynamic performance. In light of this, the study aims to investigate a more optimized solution compared to conventional structural wing designs. The design challenges faced by the aviation industry today require innovative techniques to improve flight efficiency and minimize environmental impact. This study focuses on the aeroelastic impact validation of wing trailing edge morphing, which undergoes significant structural changes to enhance performance as per mission requirements. The approach to design-concept, modeling, and construction described in this study is generalizable and requires lightweight and actively deformable structures. The objective of this work is to demonstrate the aerodynamic efficiency of an innovative structural design and trailing edge morphing concept compared to conventional wing-flap configurations. The analysis revealed that the maximum displacement at a 30-degree deflection is 47.45 mm, while the maximum stress is 21 MPa. Considering that the yield strength of ABS material is 41.14 MPa, this kerf morphing structure, with a safety factor of 2.5, can withstand both structural and aerodynamic loads. The analysis results of the flap and morph configurations showed a 27% efficiency improvement, which was confirmed through the convergence criteria in ANSYS CFX.

Posterior Midline Interspinal Fixation (PMIF) to Treat Persistent Severe Pain Due to Severe Compression Fracture of Thoracic Vertebral Body: A Case Report.

Generally, severe persistent pain due to compression fractures of the lumbar and thoracic vertebral bodies in the elderly, that fail conservative measures are treated with vertebroplasty or kyphoplasty. However, in the case reported in this paper, the compression fracture was so severe, that accurate bone needle placement into the vertebral body was felt to be difficult. In addition, there was a high risk of extravasation of the cement into the surrounding structures or blow-up of the lateral wall of the vertebral body. Therefore, a simple operation of posterior midline interspinal fixation (PMIF) was performed. The patient was a 91-year-old lady with severe pain in the mid-thoracic spine due to a severe compression fracture of the seventh thoracic vertebral body that was totally flattened in its anterior part. The patient was neurologically intact. However, she had difficulty walking, because the pain was very severe in an upright position. She was treated with a back brace and oxycodone for six weeks without any benefit. Because she was a poor candidate for vertebroplasty or kyphoplasty, a PMIF system was implanted. Postoperatively, within two weeks, her pain score dropped from 9/10 to 0/10; and from two months onwards she was completely free of pain medications until her death from an unrelated cause, 18 months after the operation. This is the first reported case of PMIF for the treatment of pain due to vertebral body compression fracture in the elderly. PMIF is a simple minimally invasive procedure without compromising the facet or any bony structure. The risk of severe complications, therefore, is remote. The success in this single case, therefore, begs for further exploration of this method in the treatment of compression fractures in the elderly.

Meta-QTL and haplo-pheno analysis reveal superior haplotype combinations associated with low grain chalkiness under high temperature in rice.

Chalk, an undesirable grain quality trait in rice, is primarily formed due to high temperatures during the grain-filling process. Owing to the disordered starch granule structure, air spaces and low amylose content, chalky grains are easily breakable during milling thereby lowering head rice recovery and its market price. Availability of multiple QTLs associated with grain chalkiness and associated attributes, provided us an opportunity to perform a meta-analysis and identify candidate genes and their alleles contributing to enhanced grain quality. From the 403 previously reported QTLs, 64 Meta-QTLs encompassing 5262 non-redundant genes were identified. MQTL analysis reduced the genetic and physical intervals and nearly 73% meta-QTLs were narrower than 5cM and 2Mb, revealing the hotspot genomic regions. By investigating expression profiles of 5262 genes in previously published datasets, 49 candidate genes were shortlisted on the basis of their differential regulation in at least two of the datasets. We identified non-synonymous allelic variations and haplotypes in 39 candidate genes across the 3K rice genome panel. Further, we phenotyped a subset panel of 60 rice accessions by exposing them to high temperature stress under natural field conditions over two Rabi cropping seasons. Haplo-pheno analysis uncovered haplotype combinations of two starch synthesis genes, GBSSI and SSIIa, significantly contributing towards the formation of grain chalk in rice. We, therefore, report not only markers and pre-breeding material, but also propose superior haplotype combinations which can be introduced using either marker-assisted breeding or CRISPR-Cas based prime editing to generate elite rice varieties with low grain chalkiness and high HRY traits.

LMTdb: A comprehensive transcriptome database for climate-resilient, nutritionally rich little millet (Panicum sumatrense).

Little millet (Panicum sumatrense) a native of Chhattisgarh, belongs to the minor millet group and is primarily known as a climate-resilient and nutritionally rich crop. However, due to the lack of enough Omic studies on the crop, the scientific community has largely remained unaware of the potential of this crop, resulting in less scope for its utilization in crop improvement programs. Looking at global warming, erratic climate change, nutritional security, and limited genetic information available, the Little Millet Transcriptome Database (LMTdb) (https://igkv.ac.in/xenom/index.aspx) was conceptualized upon completion of the transcriptome sequencing of little millet with the aim of deciphering the genetic signatures of this largely unknown crop. The database was developed with the view of providing information about the most comprehensive part of the genome, the 'Transcriptome'. The database includes transcriptome sequence information, functional annotation, microsatellite markers, DEGs, and pathway information. The database is a freely available resource that provides breeders and scientists a portal to search, browse, and query data to facilitate functional and applied Omic studies in millet crops.

Posterior Oblique Approach for Sacroiliac Joint Fusion.

Introduction Sacroiliac joint (SIJ) pain is a common source of low back pain. Though this condition can be treated with conservative measures, there is a subset of patients who fail to respond to conservative treatment. For them, surgical treatment using minimally invasive techniques could be considered. There are currently a number of SIJ fixation methods described. However, there is no case series reported on posterior oblique approach. Therefore, in this paper, the authors report their experience with the Sacrix system via the posterior oblique approach. Method In this series, 19 patients aged 44-84 years, with a median of 58 years, underwent SIJ fusion using this technique. This is a posterior oblique approach in which two screws are inserted into the ilium through the posterior part of the iliac crest and then advanced into the sacrum through the SIJ. Results The follow-up is between 7 and 30 months, with a median of 12 months. Eighteen patients had excellent pain relief. There was no complication from the procedure, and the blood loss was minimal. All eight patients who had follow-up radiographs showed solid fusion. Conclusion Posterior oblique approach for SIJ fusion is a minimally invasive procedure that proved to be effective and safe in this series. It also resulted in solid radiographic fusion, decreased pain, and improved function.

Functional Properties of Grapefruit Seed Extract Embedded Blend Membranes of Poly(vinyl alcohol)/Starch: Potential Application for Antiviral Activity in Food Safety to Fight Against COVID-19.

The poly(vinyl alcohol) (PVA) and starch-based polymeric films with a ratio of 2:8 were prepared using solution casting followed by a solvent evaporation method. Four types of membranes with varied concentrations of grapefruit seed extract (GSE) i.e., 2.5-10 wt% was incorporated in the films. The prepared membranes were assessed for transparency test, mechanical properties, surface morphology, permeability test for O2, and antimicrobial properties. The PVA/starch-10% GSE loaded film showed excellent mechanical properties showing highest 1344 ± 0.7% elongation at break but poor optical transparency with 53.8% to 68.61%. The Scanning Electron Microscopic study reveals the good compatibility between the PVA, Starch, and GSE. The gas permeability test reveals that the prepared films have shown good resistance to the O2 permeability 0.0326-0.316 Barrer at 20 kg/cm2 feed pressure for the prepared membranes showing excellent performance. By adding the little amount of GSE into the PVA/starch blend membranes showed promising antimicrobial efficacy against MNV-1. For 4 h. incubation, PVA/starch blend membranes containing 2.5%, 5%, and 10% GSE caused MNV-1 reductions of 0.92, 1.89, and 2.27 log PFU/ml, respectively. Similarly, after 24 h, the 5% and 10% GSE membranes reduced MNV-1 titers by 1.90 and 3.26 log PFU/ml, respectively. Antimicrobial tests have shown excellent performance to resist microorganisms. The water uptake capacity of the membrane is found 72% for the PVA/starch pristine membrane and is reduced to 32% for the 10% GSE embedded membrane. Since the current pandemic situation due to COVID-19 occurred by SARSCOV2, the prepared GSE incorporated polymeric blend films are the rays of hope in the packaging of food stuff.

Biomimicking Nature-Inspired Design Structures-An Experimental and Simulation Approach Using Additive Manufacturing.

Whether it is a plant- or animal-based bio-inspiration design, it has always been able to address one or more product/component optimisation issues. Today's scientists or engineers look to nature for an optimal, economically viable, long-term solution. Similarly, a proposal is made in this current work to use seven different bio-inspired structures for automotive impact resistance. All seven of these structures are derived from plant and animal species and are intended to be tested for compressive loading to achieve load-bearing capacity. The work may even cater to optimisation techniques to solve the real-time problem using algorithm-based generative shape designs built using CATIA V6 in unit dimension. The samples were optimised with Rhino 7 software and then simulated with ANSYS workbench. To carry out the comparative study, an experimental work of bioprinting in fused deposition modelling (3D printing) was carried out. The goal is to compare the results across all formats and choose the best-performing concept. The results were obtained for compressive load, flexural load, and fatigue load conditions, particularly the number of life cycles, safety factor, damage tolerance, and bi-axiality indicator. When compared to previous research, the results are in good agreement. Because of their multifunctional properties combining soft and high stiffness and lightweight properties of novel materials, novel materials have many potential applications in the medical, aerospace, and automotive sectors.

Intramural Jejunal Hematoma Causing Intermittent Bowel Obstruction-A Rare Manifestation of Warfarin Toxicity.

Patients with thromboembolic disorders are commonly on anticoagulants; hence, they are susceptible to bleeding episodes such as ecchymosis, gingival, subconjunctival bleeding, and rarely can have intramural hematoma of small bowel causing patient to present with intestinal obstruction. It is a rare cause of mechanical bowel obstruction requiring a nonsurgical management. Our patient was a 55-year-old male, a known case of thromboembolism on warfarin medication, presented with abdominal pain and vomiting. Patient's laboratory reports reflected anemia and deranged coagulation profile with prothrombin time and international normalized ratio, both being elevated. Intramural hematoma of jejunum was diagnosed by abdominal contrast-enhanced computed tomography. Conservative management was done, warfarin was stopped and vitamin K was administered. Patient received fresh frozen plasma and packed cell blood. It is important to suspect warfarin toxicity in patients on the medication who come with such presentation to avoid surgical management, which could be catastrophic due to excessive bleeding. It is important for regular monitoring of coagulation profile of such patients and to reduce prescribing other medications that can interact with warfarin. It is worth noting that novel oral anticoagulants, such as dabigatran and rivaroxaban, are associated with fewer side effects and do not require close laboratory monitoring.

Experimental and Computational Study of Mechanical and Thermal Characteristics of h-BN and GNP Infused Polymer Composites for Elevated Temperature Applications.

Polymer-based nanocomposites are being considered as replacements for conventional materials in medium to high-temperature applications. This article aims to discover the synergistic effects of reinforcements on the developed polymer-based nanocomposite. An epoxy-based polymer composite was manufactured by reinforcing graphene nanoplatelets (GNP) and h-boron nitride (h-BN) nanofillers. The composites were prepared by varying the reinforcements with the step of 0.1 from 0.1 to 0.6%. Ultrasonication was carried out to ensure the homogenous dispersion of reinforcements. Mechanical, thermal, functional, and scanning electron microscopy (SEM) analysis was carried out on the novel manufactured composites. The evaluation revealed that the polymer composite with GNP 0.2 by wt % has shown an increase in load-bearing capacity by 265% and flexural strength by 165% compared with the pristine form, and the polymer composite with GNP and h-BN 0.6 by wt % showed an increase in load-bearing capacity by 219% and flexural strength by 114% when compared with the pristine form. Furthermore, the evaluation showed that the novel prepared nanocomposite reinforced with GNP and h-BN withstands a higher temperature, around 340 °C, which is validated by thermogravimetric analysis (TGA) trials. The numerical simulation model is implemented to gather the synthesised nanocomposite's best composition and mechanical properties. The minor error between the simulation and experimental data endorses the model's validity. To demonstrate the industrial applicability of the presented material, a case study is proposed to predict the temperature range for compressor blades of gas turbine engines containing nanocomposite material as the substrate and graphene/h-BN as reinforcement particles.

A curated human cellular microRNAome based on 196 primary cell types.

BACKGROUND: An incomplete picture of the expression distribution of microRNAs (miRNAs) across human cell types has long hindered our understanding of this important regulatory class of RNA. With the continued increase in available public small RNA sequencing datasets, there is an opportunity to more fully understand the general distribution of miRNAs at the cell level. RESULTS: From the NCBI Sequence Read Archive, we obtained 6,054 human primary cell datasets and processed 4,184 of them through the miRge3.0 small RNA sequencing alignment software. This dataset was curated down, through shared miRNA expression patterns, to 2,077 samples from 196 unique cell types derived from 175 separate studies. Of 2,731 putative miRNAs listed in miRBase (v22.1), 2,452 (89.8%) were detected. Among reasonably expressed miRNAs, 108 were designated as cell specific/near specific, 59 as infrequent, 52 as frequent, 54 as near ubiquitous, and 50 as ubiquitous. The complexity of cellular microRNA expression estimates recapitulates tissue expression patterns and informs on the miRNA composition of plasma. CONCLUSIONS: This study represents the most complete reference, to date, of miRNA expression patterns by primary cell type. The data are available through the human cellular microRNAome track at the UCSC Genome Browser (https://genome.ucsc.edu/cgi-bin/hgHubConnect) and an R/Bioconductor package (https://bioconductor.org/packages/microRNAome/).

Dissecting Plasmodium yoelii Pathobiology: Proteomic Approaches for Decoding Novel Translational and Post-Translational Modifications.

Malaria is a vector-borne disease. It is caused by Plasmodium parasites. Plasmodium yoelii is a rodent model parasite, primarily used for studying parasite development in liver cells and vectors. To better understand parasite biology, we carried out a high-throughput-based proteomic analysis of P. yoelii. From the same mass spectrometry (MS)/MS data set, we also captured several post-translational modified peptides by following a bioinformatics analysis without any prior enrichment. Further, we carried out a proteogenomic analysis, which resulted in improvements to some of the existing gene models along with the identification of several novel genes. Analysis of proteome and post-translational modifications (PTMs) together resulted in the identification of 3124 proteins. The identified PTMs were found to be enriched in mitochondrial metabolic pathways. Subsequent bioinformatics analysis provided an insight into proteins associated with metabolic regulatory mechanisms. Among these, the tricarboxylic acid (TCA) cycle and the isoprenoid synthesis pathway are found to be essential for parasite survival and drug resistance. The proteogenomic analysis discovered 43 novel protein-coding genes. The availability of an in-depth proteomic landscape of a malaria pathogen model will likely facilitate further molecular-level investigations on pre-erythrocytic stages of malaria.

Stereotactic Ventriculostomy Guide.

Introduction Based on the anatomy of the frontal horn, a stereotactic ventriculostomy guidance system that does not need an elaborate setup and is suitable for ventricles of all sizes was developed. The objective of this paper is to describe this system and present the results of a cadaveric study in which this system was used. Method The system has a midline-based plate that is contoured to snugly fit the top of the head. It has two probe holders, one on each side at pre-set angles in coronal and sagittal planes, which enables the probe holders to point at the foramen of Monro. A cadaver study was done on eight donors. First, using the guidance system a 1.4 mm endoscope was inserted into the right frontal horn through a twist drill hole. Next, the scope was inserted into the right frontal horn on the same donors using the freehand method. Result With the guide, all eight ventricles were entered into on the first trial, and the foramen of Monro was visible end-on. With freehand technique: six ventricles were entered on the first try; however, the foramen of Monro was visible end-on only in one. In the other two, two to three attempts were needed. The guide facilitated 100% visibility for the end-on visibility of the foramen of Monro upon insertion and the results were statistically significant with t=7, df=7, p-value=0.000106. Conclusion This is a simple system, which is easy to use. The cadaveric study showed a high degree of accuracy to access the ventricles. The data shows significant improvement compared to the freehand technique.

Synthesis and Characterization of Microwave-Assisted Copolymer Membranes of Poly(vinyl alcohol)-g-starch-methacrylate and Their Evaluation for Gas Transport Properties.

Poly(vinyl alcohol) (PVA) is an excellent membrane-forming polymer and can be modified with potato starch and methyl acrylate monomers to obtain copolymers with improved physical and chemical properties. The study presents the synthesis of poly(vinyl alcohol)-g-starch-poly(methyl acrylate) PVA-g-St-g-PMA copolymers using microwave irradiation technique and potassium persulfate initiator. Solution casting and solvent evaporation methods were adopted for the fabrication of polyvinyl alcohol-g-starch-acrylamide composite membranes. The synthesized graft copolymer was characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, and thermal analysis. The modified nanocomposite membranes were showed very promising results with the parameters permeability and selectivity. The nanocomposite membranes exhibited the advantages of easy handling and reuse.

Sol-Gel Co-Precipitation Synthesis, Anticoagulant and Anti-Platelet Activities of Copper-Doped Nickel Manganite Nanoparticles.

Copper-substituted nickel manganites Ni(1-x)CuxMn2O4 (Ni-TCE-NPs) were produced by co-precipitation route (sol-gel) at room temperature. Ni(1-x)CuxMn2O4-Bio (NCB) NPs were studied by powder X-ray diffraction technique, scanning electron microscopy and Raman spectroscopy. XRD spectra authenticated the copper-doped nickel manganites' formation with particle size 23-28 nm. A significant decrease in the lattice parameter confirmed the doping of copper ions into the nickel manganites. Microscopy (SEM) was used to estimate the grain size, shape and uniformity, revealing the non-uniform agglomerated polygon and plate-like microstructure. The NCB-NPs showed anticoagulant activity by enhancing the coagulation time of citrated plasma of human beings. NCB-NPs with x = 0.35 and 0.45 have increased clotting time from control 133 ± 4 s to 401 ± 7 s and 3554 ± 80 s, respectively, and others around 134 s. Additionally NCB-NPs with x = 0.35, 0.45 inhibited the platelet aggregation by 80% and 92%, while remaining inhibited with only 30%. NCB-NPs did not show hemolytic activity in RBC cells intimate its non-toxic nature. Finally, NCB-NPs were non-toxic and known to exhibit anti-blood-clotting and antiplatelet activities, which can be used in the field of biomedical applications, especially as antithrombotic agents.

Laparoscopic Transgastric Resection of a Large Gastric GIST: A Case Report and Review of Literature.

Introduction Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. Their primary treatment is surgical. Case Report Here we report a case of a 36-year-old male patient who was being evaluated for weakness, anemia, and melena. Upper GI endoscopy showed a mass projecting into the lumen and an abdominal computed tomography (CT) confirmed a well-defined mass close to the lesser curvature on the posterior wall. An endoscopic ultrasound-guided fine needle aspiration suggested a diagnosis of GIST. After optimization, the patient was taken up for a laparoscopic transgastric resection of the GIST. The resected specimen measured 9.5 × 8.5 × 7.5 cm. Postoperatively, the patient recovered well and was discharged by the fifth postoperative day. Discussion While traditionally, open surgery has been advocated for GISTs, for fear of spillage and peritoneal seeding, the role of minimal access surgery has been growing in recent years. The use of a transgastric approach avoids the potential complication of luminal stenosis following a wedge resection of a tumor close to the cardia. Because lymphadenectomies are rarely required and local invasion is uncommon, a wide local resection is usually curative. Thus, a laparoscopic approach can be considered as the first line in uncomplicated GISTs, irrespective of tumor size.

Influence of Solid Lubricant Addition on Friction and Wear Response of 3D Printed Polymer Composites.

In this study, acrylonitrile butadiene styrene (ABS) and graphite powder-a solid lubricant-were filled and characterized for friction and wear responses. The fused deposition modeling (FDM) technique was utilized to synthesize ABS-graphite composites. A twin-screw extrusion approach was employed to create the composite filament of graphite-ABS that is suitable for the FDM process. Three graphite particle ratios ranging from 0% to 5% were explored in the ABS matrix. The wear and friction properties of ABS composites were examined using a pin on disc tribometer at varied sliding velocities and weights. As a result of the graphite addition in the ABS matrix, weight losses for FDM components as well as a decreased coefficient of friction were demonstrated. Furthermore, as the graphite weight percentage in the ABS matrix grows the value of friction and wear loss decreases. The wear mechanisms in graphite filled ABS composites and ABS were extensively examined using scanning electron microscopy and confocal microscopy.