Methylation microarray-based detection of clinical copy-number aberrations in CLL benchmarked to standard FISH analysis.

Copy-number aberrations (CNAs) are assessed using FISH analysis in diagnostics of chronic lymphocytic leukemia (CLL), but CNAs can also be extrapolated from Illumina BeadChips developed for genome-wide methylation microarray screening. Increasing numbers of microarray data-sets are available from diagnostic samples, making it useful to assess the potential in CNA diagnostics. We benchmarked the limitations of CNA testing from two Illumina BeadChips (EPIC and 450k) and using two common packages for analysis (conumee and ChAMP) to FISH-based assessment of 11q, 13q, and 17p deletions in 202 CLL samples.

Digital Histological Study of Neocortical Grey and White Matter Tau Burden Across Tauopathies.

3R/4R-tau species are found in Alzheimer disease (AD) and ∼50% of Lewy body dementias at autopsy (LBD+tau); 4R-tau accumulations are found in progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Digital image analysis techniques can elucidate patterns of tau pathology more precisely than traditional methods but repeatability across centers is unclear. We calculated regional percentage areas occupied by tau pathological inclusions from the middle frontal cortex (MFC), superior temporal cortex (STC), and angular gyrus (ANG) from cases from the University of Pennsylvania and the University of California San Diego with AD, LBD+tau, PSP, or CBD (n = 150) using QuPath.

Learn2Reg: Comprehensive Multi-Task Medical Image Registration Challenge, Dataset and Evaluation in the Era of Deep Learning.

Image registration is a fundamental medical image analysis task, and a wide variety of approaches have been proposed. However, only a few studies have comprehensively compared medical image registration approaches on a wide range of clinically relevant tasks. This limits the development of registration methods, the adoption of research advances into practice, and a fair benchmark across competing approaches.

Ultrasmall Cluster Model for Investigating Single Atom Catalysis: Dehydrogenation of 1-Propanamine by Size-Selected PtZrO Clusters Supported on HOPG.

The selective dehydrogenation of hydrocarbons and their functionalized derivatives is a promising pathway in the realization of endothermic fuel systems for powering important technologies such as hypersonic aircraft. The recent surge in interest in single atom catalysts (SACs) over the past decade offers the opportunity to achieve the ultimate levels of selectivity through the subnanoscale design tailoring of novel catalysts. Experimental techniques capable of investigating the fundamental nature of the active sites of novel SACs in well-controlled model studies offer the chance to reveal promising insights.

Association of Multimorbidity and Excess Mortality After Fractures Among Danish Adults.

Importance: Limited knowledge about interactions among health disorders impedes optimal patient care. Because comorbidities are common among patients 50 years and older with fractures, these fractures provide a useful setting for studying interactions among disorders.

Objective: To define multimorbidity clusters at the time of fracture and quantify the interaction between multimorbidity and fracture in association with postfracture excess mortality.

Machine learning and deep learning applications in microbiome research.

The many microbial communities around us form interactive and dynamic ecosystems called microbiomes. Though concealed from the naked eye, microbiomes govern and influence macroscopic systems including human health, plant resilience, and biogeochemical cycling. Such feats have attracted interest from the scientific community, which has recently turned to machine learning and deep learning methods to interrogate the microbiome and elucidate the relationships between its composition and function.

Association of Patient-Centered Elements of Care and Palliative Care Among Patients With Advanced Lung Cancer.

Context: Palliative care (PC) is associated with improved quality of life, survival, and decreased healthcare use at the end of life among lung cancer patients. However, the specific elements of palliative care that may contribute to these benefits are unclear.

Objectives: To evaluate the associations of PC and its setting of delivery with prescriptions of symptom management medications, advance care planning (ACP), hospice enrollment, and home health care (HHC) receipt.

Birth traits of Holstein calves compared with Holstein, Jersey, Montbéliarde, Normande, and Viking Red-sired crossbred calves.

Holstein (HO) calves, 3-breed crossbred calves of Montbéliarde, Viking Red, and HO (MVH), and 3-breed crossbred calves of Normande, Jersey, and Viking Red (NJV) were compared for gestation length (GL), calf weight at birth (CW), calving difficulty (CD), and stillbirth (SB) in 2 research herds at the University of Minnesota. Calves were born from January 2009 to December 2019. For the St.

Targeting the MYC interaction network in B-cell lymphoma via histone deacetylase 6 inhibition.

Overexpression of MYC is a genuine cancer driver in lymphomas and related to poor prognosis. However, therapeutic targeting of the transcription factor MYC remains challenging. Here, we show that inhibition of the histone deacetylase 6 (HDAC6) using the HDAC6 inhibitor Marbostat-100 (M-100) reduces oncogenic MYC levels and prevents lymphomagenesis in a mouse model of MYC-induced aggressive B-cell lymphoma.

Methylation levels assessment with Methylation-Sensitive High-Resolution Melting (MS-HRM).

Testing for disease-related DNA methylation changes provides clinically relevant information in personalized patient care. Methylation-Sensitive High-Resolution Melting (MS-HRM) is a method used for measuring methylation changes and has already been used in diagnostic settings. This method utilizes one set of primers that initiate the amplification of both methylated and non-methylated templates.

A machine learning analysis of COVID-19 mental health data.

In late December 2019, the novel coronavirus (Sars-Cov-2) and the resulting disease COVID-19 were first identified in Wuhan China. The disease slipped through containment measures, with the first known case in the United States being identified on January 20th, 2020. In this paper, we utilize survey data from the Inter-university Consortium for Political and Social Research and apply several statistical and machine learning models and techniques such as Decision Trees, Multinomial Logistic Regression, Naive Bayes, k-Nearest Neighbors, Support Vector Machines, Neural Networks, Random Forests, Gradient Tree Boosting, XGBoost, CatBoost, LightGBM, Synthetic Minority Oversampling, and Chi-Squared Test to analyze the impacts the COVID-19 pandemic has had on the mental health of frontline workers in the United States.

Comparison of 3-breed rotational crossbreds of Montbéliarde, Viking Red, and Holstein with Holstein cows fed 2 alternative diets for dry matter intake, production, and residual feed intake.

The objective of this study was to compare 3-breed rotational crossbred (CB) cows of the Montbéliarde, Viking Red, and Holstein (HO) breeds with HO cows fed 2 alternative diets for dry matter intake (DMI), fat plus protein production (CFP), body weight (BW), body condition score (BCS), feed efficiency, and residual feed intake (RFI) from 46 to 150 days in milk (DIM) during first lactation. The CB cows (n = 17) and HO cows (n = 19) calved from September 2019 to March 2020. Cows were fed either a traditional total mixed ration diet (TRAD) or a higher fiber, lower starch total mixed ration diet (HFLS).

Detection of nucleotide modifications in bacteria and bacteriophages: Strengths and limitations of current technologies and software.

RNA and DNA modifications occur in eukaryotes and prokaryotes, as well as in their viruses, and serve a wide range of functions, from gene regulation to nucleic acid protection. Although the first nucleotide modification was discovered almost 100 years ago, new and unusual modifications are still being described. Nucleotide modifications have also received more attention lately because of their increased significance, but also because new sequencing approaches have eased their detection.

A microbial supply chain for production of the anti-cancer drug vinblastine.

Monoterpene indole alkaloids (MIAs) are a diverse family of complex plant secondary metabolites with many medicinal properties, including the essential anti-cancer therapeutics vinblastine and vincristine. As MIAs are difficult to chemically synthesize, the world's supply chain for vinblastine relies on low-yielding extraction and purification of the precursors vindoline and catharanthine from the plant Catharanthus roseus, which is then followed by simple in vitro chemical coupling and reduction to form vinblastine at an industrial scale. Here, we demonstrate the de novo microbial biosynthesis of vindoline and catharanthine using a highly engineered yeast, and in vitro chemical coupling to vinblastine.

Perception of Fragmented Letters by Patients With Pathologically Confirmed Dementia With Lewy Bodies or Alzheimer Disease.

Background And Objective: Patients with dementia with Lewy bodies perform worse than those with Alzheimer disease (AD) on tests of visual perception, but the clinical utility of these tests remains unknown because studies often had clinically diagnosed groups that may inadvertently cross-contaminate Lewy body disease (LBD) with pure AD pathology, used experimental tests not easily adaptable for clinical use, and had no way to examine relationships between the severity of LBD pathology and degree of cognitive impairment. Therefore, we sought to determine whether performance on a widely used clinical test of visuoperceptual ability effectively differentiates between patients with autopsy-confirmed LBD or AD and correlates with the severity of LBD pathology.

Methods: Patients with mild to moderate dementia (n = 42) and cognitively healthy controls (n = 22) performed a Fragmented Letters Test in which they identified letters of the alphabet that were randomly visually degraded by 70% and additional visuospatial and episodic memory tests.

Influence of Unequal Amplification of Methylated and Non-Methylated Template on Performance of Pyrosequencing.

Pyrosequencing is one of the technologies widely used for quantitative methylation assessment. The protocol of pyrosequencing experiment consists of PCR amplification of a locus of interest and subsequent sequencing via synthesis of the amplified PCR product. As the PCR in this protocol utilizes one primer set for the amplification of a template originating from both methylated and non-methylated versions of the analysed locus, the unequal amplification of one of the templates may affect the methylation level assessment by pyrosequencing.

[Advanced locoregional chest wall recurrence of breast cancer].

Locoregional recurrence of breast cancer continues to be a significant clinical issue involving extensive examination programmes, modified oncologic therapy and advanced surgery. The latter includes tumour resection followed by reconstruction of the thoracic wall. The type of reconstruction depends on tumour location, depth, aetiology and whether the resection involves the stabilising osseous structures as summarised in this review.

The Spatial Distribution of Cellular Voids in the Human Otic Capsule: An Unbiased Quantification of Osteocyte-Depleted Areas.

Objective: This study aimed to describe the spatial distribution of osteocyte-depleted areas, so-called cellular voids, in the human otic capsule and compare it with that of otosclerosis.

Background: Systematic histological studies of the bony otic capsule have revealed an osteoprotegerin (OPG)-mediated inhibition of normal bone remodeling around the inner ear. The resulting accumulation of bony degeneration and dead osteocytes has been thoroughly documented, and the spatial distribution of dead osteocytes and matrix microcracks resembles that of the human ear disease otosclerosis.

Addition of point-of-care test reduces antibiotic prescription in hospitalised children with suspected respiratory tract infection: A pre-test-post-test study.

Aim: Prompt and accurate aetiological diagnostics are needed if physicians are to improve and target antibiotic treatment. We aimed to investigate whether antibiotic-prescribing decisions are improved with availability of point-of-care polymerase chain reaction (POC-PCR) diagnostic testing of children with suspected respiratory tract infection, and if it had an impact on referral for additional medical procedures.

Methods: This was a single-centre one-group pre-test-post-test study.

Antibiotic resistance genes are differentially mobilized according to resistance mechanism.

Background: Screening for antibiotic resistance genes (ARGs) in especially environmental samples with (meta)genomic sequencing is associated with false-positive predictions of phenotypic resistance. This stems from the fact that most acquired ARGs require being overexpressed before conferring resistance, which is often caused by decontextualization of putative ARGs by mobile genetic elements (MGEs). Consequent overexpression of ARGs can be caused by strong promoters often present in insertion sequence (IS) elements and integrons and the copy number effect of plasmids, which may contribute to high expression of accessory genes.

Standardized ileal digestible amino acids and digestible energy contents in two modified soy protein concentrates and soybean meal fed to growing pigs.

Six ileal-cannulated barrows (28.0 ± 1.3 kg initial BW) were used in a replicated 3 × 3 Latin square design with one additional period ( = 7 or 6) to determine standardized ileal digestible (SID) AA and digestible energy of two modified soy protein concentrates [MSPC1 and MSPC2] and soybean meal (SBM).

Genetic, Phenotypic and Metabolic Diversity of Yeasts From Wheat Flag Leaves.

The phyllosphere, the aboveground part of a plant, is a harsh environment with diverse abiotic and biotic stresses, including oscillating nutrient availability and temperature as well as exposure to UV radiation. Microbial colonization of this dynamic environment requires specific adaptive traits, including tolerance to fluctuating temperatures, the production of secondary metabolites and pigments to successfully compete with other microorganisms and to withstand abiotic stresses. Here, we isolated 175 yeasts, comprising 15 different genera, from the wheat flag leaf and characterized a selection of these for various adaptive traits such as substrate utilization, tolerance to different temperatures, biofilm formation, and antagonism toward the fungal leaf pathogen .

Strength of Dry and Wet Quartz in the Low-Temperature Plasticity Regime: Insights From Nanoindentation.

At low-temperature and high-stress conditions, quartz deformation is controlled by the kinetics of dislocation glide, that is, low-temperature plasticity (LTP). To investigate the relationship between intracrystalline HO content and the yield strength of quartz LTP, we have integrated spherical and Berkovich nanoindentation tests at room temperature on natural quartz with electron backscatter diffraction and secondary-ion mass spectrometry measurements of intracrystalline HO content. Dry (<20 wt ppm HO) and wet (20-100 wt ppm HO) crystals exhibit comparable indentation hardness.

Increased maternofoetal transfer of antibodies in a murine model of systemic lupus erythematosus, but no immune activation and neuroimmune sequelae in offspring.

Maternally transferred autoantibodies can negatively impact the development and health of offspring, increasing the risk of neurodevelopmental disorders. We used embryo transfers to examine maternofoetal immune imprinting in the autoimmune BXSB/MpJ mouse model. Anti-double-stranded DNA antibodies and total immunoglobulins were measured, using allotypes of the IgG subclass to distinguish maternally transferred antibodies from those produced endogenously.