Duplicated Palmaris Longus Muscle With Insertion Onto The Transverse Carpal Ligament: A Case Report

The palmaris longus muscle is one of the most anatomically variable muscles in the human body, with incidence ranging from 0-63.9%.  While these anatomical variations are typically benign, they are of clinical importance as they can contribute to neurovascular and biomechanical dysfunction.  We report here a duplicated palmaris longus muscle with an insertion onto the transverse carpal ligament found during cadaveric dissection in a graduate anatomy course for physical and occupational therapy students.&nbsp

CFL3D, FUN3d, and NSU3D Contributions to the Fifth Drag Prediction Workshop

Results presented at the Fifth Drag Prediction Workshop using CFL3D, FUN3D, and NSU3D are described. These are calculations on the workshop provided grids and drag adapted grids. The NSU3D results have been updated to reflect an improvement to skin friction calculation on skewed grids. FUN3D results generated after the workshop are included for custom participant generated grids and a grid from a previous workshop. Uniform grid refinement at the design condition shows a tight grouping in calculated drag, where the variation in the pressure component of drag is larger than the skin friction component. At this design condition, A fine-grid drag value was predicted with a smaller drag adjoint adapted grid via tetrahedral adaption to a metric and mixed-element subdivision. The buffet study produced larger variation than the design case, which is attributed to large differences in the predicted side-of-body separation extent. Various modeling and discretization approaches had a strong impact on predicted side-of-body separation. This large wing root separation bubble was not observed in wind tunnel tests indicating that more work is necessary in modeling wing root juncture flows to predict experiments

Development of Automatic Speech Recognition for the Documentation of Cook Islands Māori

This paper describes the process of data processing and training of an automatic speech recognition (ASR) system for Cook Islands Māori (CIM), an Indigenous language spoken by approximately 22,000 people in the South Pacific. We transcribed four hours of speech from adults and elderly speakers of the language and prepared two experiments. First, we trained three ASR systems: one statistical, Kaldi; and two based on Deep Learning, DeepSpeech and XLSR-Wav2Vec2. Wav2Vec2 tied with Kaldi for lowest character error rate (CER=6±1) and was slightly behind in word error rate (WER=23±2 versus WER=18±2 for Kaldi). This provides evidence that Deep Learning ASR systems are reaching the performance of statistical methods on small datasets, and that they can work effectively with extremely low-resource Indigenous languages like CIM. In the second experiment we used Wav2Vec2 to train models with held-out speakers. While the performance decreased (CER=15±7, WER=46±16), the system still showed considerable learning. We intend to use ASR to accelerate the documentation of CIM, using newly transcribed texts to improve the ASR and also generate teaching and language revitalization materials. The trained model is available under a license based on the Kaitiakitanga License, which provides for non-commercial use while retaining control of the model by the Indigenous community.falseMarseille, Franc

MammoSapiens: eResearch of the lactation program.

Delivering bioinformatics power to life science researchers inevitably runs into problems of limited computing resources in the context of exponentially increasing data sources, access time, costs, lack of skills and, rapidly evolving technology and software tools with poorly defined standards. In this context the development of e-facilities to best enable collaborative research often needs to be customized to specific project applications in close cooperation with the experimentalist users and, to be concerned with the storage and management of results to allow more consistency and traceability of e-results on a broad access data mining platform. Here we showcase an internet based eResearch platform using the PHP/MySQL paradigm for the collaborative, integrative and comparative analysis of lactation related gene sequences and gene expression experiments to support lactation research. We also illustrate how these resources are used, how they enable research by allowing meta-analysis of data and results and, how the bottom-up development of customized eResearch components can lead to the production of more generic functional software tools and eResearch environments for deployment to a larger number of biological research users working on other bio-systems.<br /

MammoSapiens: eResearch of the lactation program. Building online facilities for collaborative molecular and evolutionary analysis of lactation and other biological systems from gene sequences and gene expression data.

Delivering bioinformatics power to life science researchers inevitably runs into problems of limited computing resources in the context of exponentially increasing data sources, access time, costs, lack of skills and, rapidly evolving technology and software tools with poorly defined standards. In this context the development of online facilities to best enable collaborative research often needs to be customized to specific project applications in close cooperation with the experimentalist users and, to be concerned with the storage and management of results to allow more consistency and traceability of results on a broad access data mining platform. Here we showcase an Internet based research platform using the PHP/MySQL paradigm for the collaborative, integrative and comparative analysis of lactation related gene sequences and gene expression experiments to support lactation research. We also illustrate how these resources are used, how they enable research by allowing meta-analysis of data and results and, how the bottom-up development of customized eResearch components can lead to the production of more generic functional software tools and eResearch environments for deployment to a larger number of biological researchers working on other bio-systems

Quantification of spatial pharmacogene expression heterogeneity in breast tumors.

BACKGROUND: Chemotherapeutic drug concentrations vary across different regions of tumors and this is thought to be involved in development of chemotherapy resistance. Insufficient drug delivery to some regions of the tumor may be due to spatial differences in expression of genes involved in the disposition, transport, and detoxification of drugs (pharmacogenes). Therefore, in this study, we analyzed the spatial expression of 286 pharmacogenes in six breast cancer tissues using the recently developed Visium spatial transcriptomics platform to (1) determine if these pharmacogenes are expressed heterogeneously across tumor tissue and (2) to determine which pharmacogenes have the most spatial expression heterogeneity. METHODS AND RESULTS: The spatial transcriptomics technology sequences the transcriptome of 55 um diameter barcoded sections (spots) across a tissue sample. We analyzed spatial gene expression profiles of four biobank-sourced breast tumor samples in addition to two breast tumor sample datasets from 10× Genomics. We define heterogeneity as the interquartile range of read counts. Collectively, we identified 8887 spots in tumor regions, 3814 in stroma, 44 in lymphocytes, and 116 in normal regions based on pathologist annotation of the tissues. We showed statistically significant differences in expression of pharmacogenes in tumor regions compared to surrounding non-tumor regions. We also observed that the most heterogeneously expressed genes within tumor regions were involved in reactive oxygen species (ROS) handling and detoxification mechanisms. GPX4, GSTP1, MGST3, SOD1, CYP4Z1, CYB5R3, GSTK1, and NAT1 showed the most heterogeneous expression within tumor regions. CONCLUSIONS: The heterogeneous expression of these pharmacogenes may have important implications for cancer therapy due to their ability to impact drug distribution and efficacy throughout the tumor. Our results suggest that chemoresistance caused by expression of GPX4, GSTP1, MGST3, and SOD1 may be intrinsic, not acquired, since the heterogeneity is not specific to chemotherapy-treated samples or cell type. Additionally, we identified candidate chemoresistance pharmacogenes that can be further tested through focused follow-up studies

New directions in cellular therapy of cancer: a summary of the summit on cellular therapy for cancer

A summit on cellular therapy for cancer discussed and presented advances related to the use of adoptive cellular therapy for melanoma and other cancers. The summit revealed that this field is advancing rapidly. Conventional cellular therapies, such as tumor infiltrating lymphocytes (TIL), are becoming more effective and more available. Gene therapy is becoming an important tool in adoptive cell therapy. Lymphocytes are being engineered to express high affinity T cell receptors (TCRs), chimeric antibody-T cell receptors (CARs) and cytokines. T cell subsets with more naïve and stem cell-like characteristics have been shown in pre-clinical models to be more effective than unselected populations and it is now possible to reprogram T cells and to produce T cells with stem cell characteristics. In the future, combinations of adoptive transfer of T cells and specific vaccination against the cognate antigen can be envisaged to further enhance the effectiveness of these therapies

Life-Threatening Docetaxel Toxicity in a Patient With Reduced-Function CYP3A Variants: A Case Report.

Docetaxel therapy occasionally causes severe and life-threatening toxicities. Some docetaxel toxicities are related to exposure, and inter-individual variability in exposure has been described based on genetic variation and drug-drug interactions that impact docetaxel clearance. Cytochrome P450 3A4 (CYP3A4) and CYP3A5 metabolize docetaxel into inactive metabolites, and this is the primary mode of docetaxel clearance. Supporting their role in these toxicities, increased docetaxel toxicities have been found in patients with reduced- or loss-of-function variants in CYP3A4 and CYP3A5. However, since these variants in CYP3A4 are rare, little is known about the safety of docetaxel in patients who are homozygous for the reduced-function CYP3A4 variants. Here we present a case of life-threatening (grade 4) pneumonitis, dyspnea, and neutropenia resulting from a single dose of docetaxel. This patient was (1) homozygous for CYP3A4*22, which causes reduced expression and is associated with increased docetaxel-related adverse events, (2) heterozygous for CYP3A4*3, a rare reduced-function missense variant, and (3) homozygous for CYP3A5*3, a common loss of function splicing defect that has been associated with increased docetaxel exposure and adverse events. The patient also carried functional variants in other genes involved in docetaxel pharmacokinetics that may have increased his risk of toxicity. We identified one additional CYP3A4*22 homozygote that received docetaxel in our research cohort, and present this case of severe hematological toxicity. Furthermore, the one other CYP3A4*22 homozygous patient we identified from the literature died from docetaxel toxicity. This case report provides further evidence for the need to better understand the impact of germline CYP3A variants in severe docetaxel toxicity and supports using caution when treating patients with docetaxel who have genetic variants resulting in CYP3A poor metabolizer phenotypes

Congruence of additive and non-additive effects on gene expression estimated from pedigree and SNP data

There is increasing evidence that heritable variation in gene expression underlies genetic variation in susceptibility to disease. Therefore, a comprehensive understanding of the similarity between relatives for transcript variation is warranted-in particular, dissection of phenotypic variation into additive and non-additive genetic factors and shared environmental effects. We conducted a gene expression study in blood samples of 862 individuals from 312 nuclear families containing MZ or DZ twin pairs using both pedigree and genotype information. From a pedigree analysis we show that the vast majority of genetic variation across 17,994 probes is additive, although non-additive genetic variation is identified for 960 transcripts. For 180 of the 960 transcripts with non-additive genetic variation, we identify expression quantitative trait loci (eQTL) with dominance effects in a sample of 339 unrelated individuals and replicate 31% of these associations in an independent sample of 139 unrelated individuals. Over-dominance was detected and replicated for a trans association between rs12313805 and ETV6, located 4MB apart on chromosome 12. Surprisingly, only 17 probes exhibit significant levels of common environmental effects, suggesting that environmental and lifestyle factors common to a family do not affect expression variation for most transcripts, at least those measured in blood. Consistent with the genetic architecture of common diseases, gene expression is predominantly additive, but a minority of transcripts display non-additive effects