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Objective. In the context of primary in-hospital trauma management timely reading of computed tomography (CT) images is critical. However, assessment of the spine is time consuming, fractures can be very subtle, and the potential for under-diagnosis or delayed diagnosis is relevant. Artificial intelligence is increasingly employed to assist radiologists with the detection of spinal fractures and prioritization of cases. Currently, algorithms focusing on the cervical spine are commercially available. A common approach is the vertebra-wise classification. Instead of a classification task, we formulate fracture detection as a segmentation task aiming to find and display all individual fracture locations presented in the image. Approach. Based on 195 CT examinations, 454 cervical spine fractures were identified and annotated by radiologists at a tertiary trauma center. We trained for the detection a U-Net via four-fold-cross validation to segment spine fractures and the spine via a multi-task loss. We further compared advantages of two image reformation approaches-straightened curved planar reformatted (CPR) around the spine and spinal canal aligned volumes of interest (VOI)-to achieve a unified vertebral alignment in comparison to processing the Cartesian data directly. Main results. Of the three data versions (Cartesian, reformatted, VOI) the VOI approach showed the best detection rate and a reduced computation time. The proposed algorithm was able to detect 87.2% of cervical spine fractures at an average number of false positives of 3.5 per case. Evaluation of the method on a public spine dataset resulted in 0.9 false positive detections per cervical spine case. Significance. The display of individual fracture locations as provided with high sensitivity by the proposed voxel classification based fracture detection has the potential to support the trauma CT reading workflow by reducing missed findings., (© 2023 Institute of Physics and Engineering in Medicine.)

Objective To preserve residual hearing in cochlear implant surgery, the electrode design has been refined, and an atraumatic insertion has become one aspect of cochlear implant research. Previous studies have described the effect of insertion speed and opening of the round window membrane on intracochlear pressure changes. The aim of our current study was to observe intracochlear pressure changes due to different cochlear implant electrodes in an artificial cochlear model with stable surrounding factors. Study Design Prospective controlled study. Setting Tertiary referral center. Subjects and Methods The experiments were performed in an artificial cochlear model with a pressure sensor in the apical area. With straight and perimodiolar electrode arrays, 5 insertions with the same insertion speed and 5 insertions over the same time were performed. Results With the perimodiolar high-volume electrode, significantly greater intracochlear fluid pressure changes were observed than with the straight electrode. Compared with the straight electrode, the perimodiolar electrode induces significantly higher pressure peaks (1.12 ± 0.15 vs 0.86 ± 0.05 mm Hg, P = .006) and significantly higher amplitudes (0.38 ± 0.07 vs 0.09 ± 0.07 mm Hg, P < .001). Conclusion The reliable preservation of residual hearing is an important multifactorial challenge in modern cochlear implant surgery. Insertion speed, handling, and electrode design are known to influence the preservation of residual hearing. In our artificial model experiments, we could prove objectively that the volume of the electrodes has a significant influence on the intracochlear pressure changes during cochlear implantation.

Conclusion: Based on this model experiment, a small tip and low volume electrode show lowest intra-cochlear pressure values. Insertional support by a tool minimizes fast pressure changes. Higher electrodes volumes affect slow and fast pressure changes as well., Objective: Insertion causing low intra-cochlear pressure is assumed to be important for atraumatic cochlear implant surgery to preserve residual hearing. Cochlear implant electrodes differ in terms of parameters like tip size, length, volume, and technique of insertion. The aim of this study was to observe the effect of different cochlear implant electrodes on insertional intra-cochlear pressure in a cochlear model., Materials and Methods: Cochlear implant electrode insertions were performed in an artificial cochlear model and intra-cochlear pressure changes were recorded in parallel with a micro-pressure sensor positioned in the apical region of the cochlear model to follow the maximum values, temporal changes, maximum amplitude, and frequency of changes in intra-cochlear pressure. Insertions were performed with four different electrodes (Advanced Bionics 1j, Helix, HFMS, and LW23)., Results: This study found statistically significant differences in the occurrence of initial maximum pressure values correlating with the electrode tip size. The different electrodes and the technique of insertion significantly affected the occurrence of maximum value, amplitude, and frequency of intra-cochlear pressure occurrence.

Conclusion: Over time, a homogenous increase in intracochlear pressure was seen in every experiment. Significant reductions in terms of amplitude variation and insertion depth were observed over time, using the one-point-supported insertion method. The frequency of peaks between the thirds was significantly lower when using the two-points-supported insertion method., Objectives: The preservation of residual hearing and minimization of intracochlear trauma are two of the major goals in modern cochlear implantation (CI) surgery. It is assumed that intracochlear pressure measurements yield information about the intracochlear behavior of the electrode itself in the cochlea. The aim of this study was to investigate temporal intracochlear fluid pressure changes using two different kinds of insertion conditions., Method: Cochlear implantations with the Advanced Bionics IJ ® electrode were performed in an artificial cochlear model with a constant insertional speed of 0.5 mm/s provided by a linear actor. Amplitude pressure changes and number of pressure peaks were evaluated for every part., Result: Intracochlear fluid pressure changes are assumed to affect the preservation of residual hearing and should be minimized. The stability and reduction of movement of a lateral wall IJ ® electrode increase at deeper insertion and affect intracochlear fluid pressure amplitude.

Background: A high-throughput genotyping platform is needed to enable marker-assisted breeding in the allo-octoploid cultivated strawberry Fragaria × ananassa. Short-read sequences from one diploid and 19 octoploid accessions were aligned to the diploid Fragaria vesca 'Hawaii 4' reference genome to identify single nucleotide polymorphisms (SNPs) and indels for incorporation into a 90 K Affymetrix® Axiom® array. We report the development and preliminary evaluation of this array., Results: About 36 million sequence variants were identified in a 19 member, octoploid germplasm panel. Strategies and filtering pipelines were developed to identify and incorporate markers of several types: di-allelic SNPs (66.6%), multi-allelic SNPs (1.8%), indels (10.1%), and ploidy-reducing "haploSNPs" (11.7%). The remaining SNPs included those discovered in the diploid progenitor F. iinumae (3.9%), and speculative "codon-based" SNPs (5.9%). In genotyping 306 octoploid accessions, SNPs were assigned to six classes with Affymetrix's "SNPolisher" R package. The highest quality classes, PolyHigh Resolution (PHR), No Minor Homozygote (NMH), and Off-Target Variant (OTV) comprised 25%, 38%, and 1% of array markers, respectively. These markers were suitable for genetic studies as demonstrated in the full-sib family 'Holiday' × 'Korona' with the generation of a genetic linkage map consisting of 6,594 PHR SNPs evenly distributed across 28 chromosomes with an average density of approximately one marker per 0.5 cM, thus exceeding our goal of one marker per cM., Conclusions: The Affymetrix IStraw90 Axiom array is the first high-throughput genotyping platform for cultivated strawberry and is commercially available to the worldwide scientific community. The array's high success rate is likely driven by the presence of naturally occurring variation in ploidy level within the nominally octoploid genome, and by effectiveness of the employed array design and ploidy-reducing strategies. This array enables genetic analyses including generation of high-density linkage maps, identification of quantitative trait loci for economically important traits, and genome-wide association studies, thus providing a basis for marker-assisted breeding in this high value crop.

High-density oligonucleotide microarrays enable simultaneous monitoring of expression levels of tens of thousands of transcripts. For accurate detection and quantitation of transcripts in the presence of cellular mRNA, it is essential to design microarrays whose oligonucleotide probes produce hybridization intensities that accurately reflect the concentration of original mRNA. We present a model-based approach that predicts optimal probes by using sequence and empirical information. We constructed a thermodynamic model for hybridization behavior and determined the influence of empirical factors on the effective fitting parameters. We designed Affymetrix GeneChip probe arrays that contained all 25-mer probes for hundreds of human and yeast transcripts and collected data over a 4,000-fold concentration range. Multiple linear regression models were built to predict hybridization intensities of each probe at given target concentrations, and each intensity profile is summarized by a probe response metric. We selected probe sets to represent each transcript that were optimized with respect to responsiveness, independence (degree to which probe sequences are nonoverlapping), and uniqueness (lack of similarity to sequences in the expressed genomic background). We show that this approach is capable of selecting probes with high sensitivity and specificity for high-density oligonucleotide arrays.

The functions of many open reading frames (ORFs) identified in genome-sequencing projects are unknown. New, whole-genome approaches are required to systematically determine their function. A total of 6925 Saccharomyces cerevisiae strains were constructed, by a high-throughput strategy, each with a precise deletion of one of 2026 ORFs (more than one-third of the ORFs in the genome). Of the deleted ORFs, 17 percent were essential for viability in rich medium. The phenotypes of more than 500 deletion strains were assayed in parallel. Of the deletion strains, 40 percent showed quantitative growth defects in either rich or minimal medium.

A highly reliable and efficient technology has been developed for high-throughput DNA polymorphism screening and large-scale genotyping. Photolithographic synthesis has been used to generate miniaturized, high-density oligonucleotide arrays. Dedicated instrumentation and software have been developed for array hybridization, fluorescent detection, and data acquisition and analysis. Specific oligonucleotide probe arrays have been designed to rapidly screen human STSs, known genes and full-length cDNAs. This has led to the identification of several thousand biallelic single-nucleotide polymorphisms (SNPs). Meanwhile, a rapid and robust method has been developed for genotyping these SNPs using oligonucleotide arrays. Each allele of an SNP marker is represented on the array by a set of perfect match and mismatch probes. Prototype genotyping chips have been produced to detect 400, 600 and 3000 of these SNPs. Based on the preliminary results, using oligonucleotide arrays to genotype several thousand polymorphic loci simultaneously appears feasible.

Single-nucleotide polymorphisms (SNPs) are the most frequent type of variation in the human genome, and they provide powerful tools for a variety of medical genetic studies. In a large-scale survey for SNPs, 2.3 megabases of human genomic DNA was examined by a combination of gel-based sequencing and high-density variation-detection DNA chips. A total of 3241 candidate SNPs were identified. A genetic map was constructed showing the location of 2227 of these SNPs. Prototype genotyping chips were developed that allow simultaneous genotyping of 500 SNPs. The results provide a characterization of human diversity at the nucleotide level and demonstrate the feasibility of large-scale identification of human SNPs.

The genomic sequence of the budding yeast Saccharomyces cerevisiae has been used to design and synthesize high-density oligonucleotide arrays for monitoring the expression levels of nearly all yeast genes. This direct and highly parallel approach involves the hybridization of total mRNA populations to a set of four arrays that contain a total of more than 260,000 specifically chosen oligonucleotides synthesized in situ using light-directed combinatorial chemistry. The measurements are quantitative, sensitive, specific, and reproducible. Expression levels ranging from less than 0.1 copies to several hundred copies per cell have been measured for cells grown in rich and minimal media. Nearly 90% of all yeast mRNAs are observed to be present under both conditions, with approximately 50% present at levels between 0.1 and 1 copy per cell. Many of the genes observed to be differentially expressed under these conditions are expected, but large differences are also observed for many previously uncharacterized genes.

Increasing evidence suggests that the retinoid-X receptors (RXR-alpha,-beta,-gamma) play a crucial role in regulating the transcriptional activity of several steroid hormone receptors, including the receptors for retinoic acid (RAR-alpha,-beta,-gamma), 1,25-dihydroxyvitamin D3 and thyroid hormone. We investigated the localization of the different types of RXR-alpha,-beta,-gamma and RAR-alpha,-beta,-gamma proteins in frozen sections of normal human skin (n = 12) in situ, applying recently raised corresponding specific monoclonal antibodies and an immunohistochemical technique that we established for the detection of these nuclear receptors. Our findings indicate that RXR-alpha,-beta,-gamma and RAR-alpha,-beta,-gamma proteins can be detected by immunohistochemistry in normal human skin. In contrast to RXR-alpha,-beta,-gamma as well as RAR-alpha and RAR-gamma proteins that were consistently detected in cell layers of the viable epidermis, RAR-beta was only focally demonstrated in single epidermal cells in three out of 12 biopsies analysed. Immunohistochemical labelling of RAR-alpha,-beta,-gamma and RXR-alpha,-beta,-gamma proteins in epidermal nuclei was also pronounced in the stratum granulosum, suggesting a function of RXR and RAR proteins in the transition from proliferation to differatiation in epidermal keratinocytes. Expression of RXRs and RARs in hair follicles, sebaceous glands and endothelial cell points to a biological function from these nuclear receptors to hair growth as well as to the physiology of sebaceous glands and endothelial cells.

A quantitative and highly parallel method for analysing deletion mutants has been developed to aid in determining the biological function of thousands of newly identified open reading frames (ORFs) in Saccharomyces cerevisiae. This approach uses a PCR targeting strategy to generate large numbers of deletion strains. Each deletion strain is labelled with a unique 20-base tag sequence that can be detected by hybridization to a high-density oligonucleotide array. The tags serve as unique identifiers (molecular bar codes) that allow analysis of large numbers of deletion strains simultaneously through selective growth conditions. Hybridization experiments show that the arrays are specific, sensitive and quantitative. A pilot study with 11 known yeast genes suggests that the method can be extended to include all of the ORFs in the yeast genome, allowing whole genome analysis with a single selective growth condition and a single hybridization.

The human genome encodes approximately 100,000 different genes, and at least partial sequence information for nearly all will be available soon. Sequence information alone, however, is insufficient for a full understanding of gene function, expression, regulation, and splice-site variation. Because cellular processes are governed by the repertoire of expressed genes, and the levels and timing of expression, it is important to have experimental tools for the direct monitoring of large numbers of mRNAs in parallel. We have developed an approach that is based on hybridization to small, high-density arrays containing tens of thousands of synthetic oligonucleotides. The arrays are designed based on sequence information alone and are synthesized in situ using a combination of photolithography and oligonucleotide chemistry. RNAs present at a frequency of 1:300,000 are unambiguously detected, and detection is quantitative over more than three orders of magnitude. This approach provides a way to use directly the growing body of sequence information for highly parallel experimental investigations. Because of the combinatorial nature of the chemistry and the ability to synthesize small arrays containing hundreds of thousands of specifically chosen oligonucleotides, the method is readily scalable to the simultaneous monitoring of tens of thousands of genes.

A technique for the immunohistochemical detection of retinoic acid receptor alpha in cryostat sections of normal human skin in situ has been developed. A highly specific mouse monoclonal antibody, directed against the F region of retinoic acid receptor alpha, was used and a panel of 10 fixation protocols investigated. A three-step protocol, consisting of sequential fixation in 3.7% paraformaldehyde, methanol and acetone, revealed strong nuclear immunoreactivity in epidermal keratinocytes and other cell types present in normal human skin. Other fixation protocols, including fixation regimens using formaldehyde or Carnoy's solution, were less suitable or unsuitable for detection of the receptor in cryostat sections of human skin.