Real world validation of an AI-based CT hemorrhage detection tool.

Introduction: Intracranial hemorrhage (ICH) is a potentially life-threatening medical event that requires expedited diagnosis with computed tomography (CT). Automated medical imaging triaging tools can rapidly bring scans containing critical abnormalities, such as ICH, to the attention of radiologists and clinicians. Here, we retrospectively investigated the real-world performance of VeriScout™, an artificial intelligence-based CT hemorrhage detection and triage tool. Methods: Ground truth for the presence or absence of ICH was iteratively determined by expert consensus in an unselected dataset of 527 consecutively acquired non-contrast head CT scans, which were sub-grouped according to the presence of artefact, post-operative features and referral source. The performance of VeriScout™ was compared with the ground truths for all groups. Results: VeriScout™ detected hemorrhage with a sensitivity of 0.92 (CI 0.84-0.96) and a specificity of 0.96 (CI 0.94-0.98) in the global dataset, exceeding the sensitivity of general radiologists (0.88) with only a minor relative decrement in specificity (0.98). Crucially, the AI tool detected 13/14 cases of subarachnoid hemorrhage, a potentially fatal condition that is often missed in emergency department settings. There was no decrement in the performance of VeriScout™ in scans containing artefact or postoperative change. Using an integrated informatics platform, VeriScout™ was deployed into the existing radiology workflow. Detected hemorrhage cases were flagged in the hospital radiology information system (RIS) and relevant, annotated, preview images made available in the picture archiving and communications system (PACS) within 10 min. Conclusion: AI-based radiology worklist prioritization for critical abnormalities, such as ICH, may enhance patient care without adding to radiologist or clinician burden.

Ultra-High-Field Neuroimaging Reveals Fine-Scale Processing for 3D Perception.

Binocular disparity provides critical information about three-dimensional (3D) structures to support perception and action. In the past decade significant progress has been made in uncovering human brain areas engaged in the processing of binocular disparity signals. Yet, the fine-scale brain processing underlying 3D perception remains unknown. Here, we use ultra-high-field (7T) functional imaging at submillimeter resolution to examine fine-scale BOLD fMRI signals involved in 3D perception. In particular, we sought to interrogate the local circuitry involved in disparity processing by sampling fMRI responses at different positions relative to the cortical surface (i.e., across cortical depths corresponding to layers). We tested for representations related to 3D perception by presenting participants (male and female, N = 8) with stimuli that enable stable stereoscopic perception [i.e., correlated random dot stereograms (RDS)] versus those that do not (i.e., anticorrelated RDS). Using multivoxel pattern analysis (MVPA), we demonstrate cortical depth-specific representations in areas V3A and V7 as indicated by stronger pattern responses for correlated than for anticorrelated stimuli in upper rather than deeper layers. Examining informational connectivity, we find higher feedforward layer-to-layer connectivity for correlated than anticorrelated stimuli between V3A and V7. Further, we observe disparity-specific feedback from V3A to V1 and from V7 to V3A. Our findings provide evidence for the role of V3A as a key nexus for disparity processing, which is implicated in feedforward and feedback signals related to the perceptual estimation of 3D structures.SIGNIFICANCE STATEMENT Binocular vision plays a significant role in supporting our interactions with the surrounding environment. The fine-scale neural mechanisms that underlie the brain's skill in extracting 3D structures from binocular signals are poorly understood. Here, we capitalize on recent advances in ultra-high-field functional imaging to interrogate human brain circuits involved in 3D perception at submillimeter resolution. We provide evidence for the role of area V3A as a key nexus for disparity processing, which is implicated in feedforward and feedback signals related to the perceptual estimation of 3D structures from binocular signals. These fine-scale measurements help bridge the gap between animal neurophysiology and human fMRI studies investigating cross-scale circuits, from micro circuits to global brain networks for 3D perception.

A protocol for ultra-high field laminar fMRI in the human brain.

Ultra-high field (UHF) neuroimaging affords the sub-millimeter resolution that allows researchers to interrogate brain computations at a finer scale than that afforded by standard fMRI techniques. Here, we present a step-by-step protocol for using UHF imaging (Siemens Terra 7T scanner) to measure activity in the human brain. We outline how to preprocess the data using a pipeline that combines tools from SPM, FreeSurfer, ITK-SNAP, and BrainVoyager and correct for vasculature-related confounders to improve the spatial accuracy of the fMRI signal. For complete details on the use and execution of this protocol, please refer to Jia et al. (2020) and Zamboni et al. (2020).

Recurrent Processing Drives Perceptual Plasticity.

Learning and experience are critical for translating ambiguous sensory information from our environments to perceptual decisions. Yet evidence on how training molds the adult human brain remains controversial, as fMRI at standard resolution does not allow us to discern the finer scale mechanisms that underlie sensory plasticity. Here, we combine ultra-high-field (7T) functional imaging at sub-millimeter resolution with orientation discrimination training to interrogate experience-dependent plasticity across cortical depths that are known to support dissociable brain computations. We demonstrate that learning alters orientation-specific representations in superficial rather than middle or deeper V1 layers, consistent with recurrent plasticity mechanisms via horizontal connections. Further, learning increases feedforward rather than feedback layer-to-layer connectivity in occipito-parietal regions, suggesting that sensory plasticity gates perceptual decisions. Our findings reveal finer scale plasticity mechanisms that re-weight sensory signals to inform improved decisions, bridging the gap between micro- and macro-circuits of experience-dependent plasticity.

Exploiting loss of heterozygosity for allele-selective colorectal cancer chemotherapy.

Cancer chemotherapy targeting frequent loss of heterozygosity events is an attractive concept, since tumor cells may lack enzymatic activities present in normal constitutional cells. To find exploitable targets, we map prevalent genetic polymorphisms to protein structures and identify 45 nsSNVs (non-synonymous small nucleotide variations) near the catalytic sites of 17 enzymes frequently lost in cancer. For proof of concept, we select the gastrointestinal drug metabolic enzyme NAT2 at 8p22, which is frequently lost in colorectal cancers and has a common variant with 10-fold reduced activity. Small molecule screening results in a cytotoxic kinase inhibitor that impairs growth of cells with slow NAT2 and decreases the growth of tumors with slow NAT2 by half as compared to those with wild-type NAT2. Most of the patient-derived CRC cells expressing slow NAT2 also show sensitivity to 6-(4-aminophenyl)-N-(3,4,5-trimethoxyphenyl)pyrazin-2-amine (APA) treatment. These findings indicate that the therapeutic index of anti-cancer drugs can be altered by bystander mutations affecting drug metabolic genes.

Genetically-defined novel oral squamous cell carcinoma cell lines for the development of molecular therapies.

Emerging biological and translational insights from large sequencing efforts underscore the need for genetically-relevant cell lines to study the relationships between genomic alterations of tumors, and therapeutic dependencies. Here, we report a detailed characterization of a novel panel of clinically annotated oral squamous cell carcinoma (OSCC) cell lines, derived from patients with diverse ethnicity and risk habits. Molecular analysis by RNAseq and copy number alterations (CNA) identified that the cell lines harbour CNA that have been previously reported in OSCC, for example focal amplications in 3q, 7p, 8q, 11q, 20q and deletions in 3p, 5q, 8p, 18q. Similarly, our analysis identified the same cohort of frequently mutated genes previously reported in OSCC including TP53, CDKN2A, EPHA2, FAT1, NOTCH1, CASP8 and PIK3CA. Notably, we identified mutations (MLL4, USP9X, ARID2) in cell lines derived from betel quid users that may be associated with this specific risk factor. Gene expression profiles of the ORL lines also aligned with those reported for OSCC. By focusing on those gene expression signatures that are predictive of chemotherapeutic response, we observed that the ORL lines broadly clustered into three groups (cell cycle, xenobiotic metabolism, others). The ORL lines noted to be enriched in cell cycle genes responded preferentially to the CDK1 inhibitor RO3306, by MTT cell viability assay. Overall, our in-depth characterization of clinically annotated ORL lines provides new insight into the molecular alterations synonymous with OSCC, which can facilitate in the identification of biomarkers that can be used to guide diagnosis, prognosis, and treatment of OSCC.

M-Protein Analysis of Streptococcus pyogenes Isolates Associated with Acute Rheumatic Fever in New Zealand.

We applied an emm cluster typing system to group A Streptococcus strains in New Zealand, including those associated with acute rheumatic fever (ARF). We observed few so-called rheumatogenic emm types but found a high proportion of emm types previously associated with pyoderma, further suggesting a role for skin infection in ARF.

Community perceptions of a rural medical school: a pilot qualitative study.

BACKGROUND: This paper explores local community perceptions of a relatively new rural medical school. For the purposes of this paper, community engagement is conceptualized as involvement in planning, delivering, and evaluating the medical program. Although there are several reviews of patient involvement in medical curricula development, this study was designed to pilot an approach to exploring the perspectives of well members of the community in the transition of institutional policy on community engagement to one medical school. METHODS: An advertisement in the local newspaper invited volunteers to participate in a telephone interview about the new medical school. An independent researcher external to the medical school conducted the interviews using a topic guide. Audio recordings were not made, but detailed notes including verbatim statements were recorded. At least two research team members analyzed interview records for emergent themes. Human research ethics approval was obtained. RESULTS: Twelve interviews were conducted. Participants offered rich imaginings on the role of the school and expectations and opportunities for students. Most participants expressed strong and positive views, especially in addressing long-term health workforce issues. It was considered important that students live, mix, and study in the community. Some participants had very clear ideas about the need of the school to address specified needs, such as indigenous health, obesity, aging, drug and alcohol problems, teenage pregnancy, ethnic diversity, and working with people of low socioeconomic status. CONCLUSION: This study has initiated a dialogue with potential partners in the community, which can be built upon to shape the medical school's mission and contribution to the society it serves. The telephone interview approach and thematic analysis yielded valuable insights and is recommended for further studies. Our study was limited by its small study size and the single recruitment source. The community is a rich resource for medical education, but there is a dearth of literature on the perspectives of the community and its role in medical education.

Epidural anesthesia with intravenous dexmedetomidine sedation in the successful anesthetic management of MRI-guided focused ultrasound ablation of early prostatic cancer.

We report on five patients who underwent MRI-guided focused ultrasound ablation of prostatic cancer under epidural anesthesia with intravenous dexmedetomidine sedation. This pioneering procedure requires an immobile therapeutic field with adequate sedation and analgesia provided to the patients. Duration of the procedure is longer compared to diagnostic MRI scans. In combination with epidural anesthesia, dexmedetomidine was used to provide moderate levels of sedation without causing respiratory depression or hemodynamic instability, and was useful in preventing shivering. The pharmacological properties of dexmedetomidine contribute to make this technique safe and effective.