tbuckley/cabot-search huggingface dataset:
Evaluation of Deep Learning Models for Identifying Surgical Actions and Measuring Performance
Authors: Shuja Khalid, Mitchell Goldenberg, Teodor Grantcharov, Babak Taati, Frank Rudzicz
Journal: JAMA Network Open (2020)

<h3>Importance</h3> When evaluating surgeons in the operating room, experienced physicians must rely on live or recorded video to assess the surgeon’s technical performance, an approach prone to subjectivity and error. Owing to the large number of surgical procedures performed daily, it is infeasible to review every procedure; therefore, there is a tremendous loss of invaluable performance data that would otherwise be useful for improving surgical safety. <h3>Objective</h3> To evaluate a framework for assessing surgical video clips by categorizing them based on the surgical step being performed and the level of the surgeon’s competence. <h3>Design, Setting, and Participants</h3> This quality improvement study assessed 103 video clips of 8 surgeons of various levels performing knot tying, suturing, and needle passing from the Johns Hopkins University–Intuitive Surgical Gesture and Skill Assessment Working Set. Data were collected before 2015, and data analysis took place from March to July 2019. <h3>Main Outcomes and Measures</h3> Deep learning models were trained to estimate categorical outputs such as performance level (ie, novice, intermediate, and expert) and surgical actions (ie, knot tying, suturing, and needle passing). The efficacy of these models was measured using precision, recall, and model accuracy. <h3>Results</h3> The provided architectures achieved accuracy in surgical action and performance calculation tasks using only video input. The embedding representation had a mean (root mean square error [RMSE]) precision of 1.00 (0) for suturing, 0.99 (0.01) for knot tying, and 0.91 (0.11) for needle passing, resulting in a mean (RMSE) precision of 0.97 (0.01). Its mean (RMSE) recall was 0.94 (0.08) for suturing, 1.00 (0) for knot tying, and 0.99 (0.01) for needle passing, resulting in a mean (RMSE) recall of 0.98 (0.01). It also estimated scores on the Objected Structured Assessment of Technical Skill Global Rating Scale categories, with a mean (RMSE) precision of 0.85 (0.09) for novice level, 0.67 (0.07) for intermediate level, and 0.79 (0.12) for expert level, resulting in a mean (RMSE) precision of 0.77 (0.04). Its mean (RMSE) recall was 0.85 (0.05) for novice level, 0.69 (0.14) for intermediate level, and 0.80 (0.13) for expert level, resulting in a mean (RMSE) recall of 0.78 (0.03). <h3>Conclusions and Relevance</h3> The proposed models and the accompanying results illustrate that deep machine learning can identify associations in surgical video clips. These are the first steps to creating a feedback mechanism for surgeons that would allow them to learn from their experiences and refine their skills.
Abstract C52: The radioprotector GC4419 enhances the response of PDAC tumors to high dose per fraction radiation exposure
Authors: Michael D. Story, Brock J. Sishc
Journal: Cancer Research (2019)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths in the United States, with an estimated 5-year overall survival rate of ~6%. While surgery followed by adjuvant therapy is the standard of care, most patients present with advanced disease. Recent clinical trials have demonstrated that the traditional radiation dose limit of 50.4 Gy to tumors located at the head of the pancreas is not sufficient to generate tumor control at doses tolerable to the jejunum; however, doses exceeding 60 Gy, particularly when delivered as stereotactic body radiation therapy (SBRT), drastically enhance progression free-survival at 2 years. Here, we present evidence that the radioprotector GC4419 (Galera Therapeutics, St. Louis, MO) whose enantiomer, GC4403, has demonstrated radioprotective properties against GI toxicity, sensitizes PDAC cells and xenografts to radiation exposure. Furthermore, combination therapy with immune oncology agents targeting the PD-L1 pathway enhanced the response of Panc02 tumors (syngeneic to C57.BL/6 mice) to combined radiation and immune therapy. These results present the foundation for a newly initiated dose-escalation clinical trial for treating PDAC tumors with GC4419 and SBRT. Citation Format: Michael D. Story, Brock J. Sishc. The radioprotector GC4419 enhances the response of PDAC tumors to high dose per fraction radiation exposure [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr C52.
Computerised speech and language therapy can help people with aphasia find words following a stroke
Authors: Rob Cook, Peter Davidson, Rosie Martin
Journal: BMJ (2020)

The study Palmer R, Dimairo M, Cooper C, et al. Self-managed, computerised speech and language therapy for patients with chronic aphasia post-stroke compared with usual care or attention control (Big CACTUS): a multicentre, single-blinded, randomised controlled trial. Lancet Neurol 2019;18:821-33. This project was funded by the NIHR Health Technology Assessment Programme (project number 12/21/01) and the Tavistock Trust for Aphasia. To read the full NIHR Signal, go to: https://discover.dc.nihr.ac.uk/content/signal-000864/after-a-stroke-computerised-speech-and-language-therapy-can-help-people-find-words
Abstract P1-21-02: Distinct methylation and copy number alteration patterns in phyllodes tumors of the breast and its mimics
Authors: Simone Muenst, Tatjana Vlajnic, Savas Deniz Soysal, Stefan Frank, Jürgen Hench
Journal: Cancer Research (2020)

Abstract Background: Phyllodes tumor (PT), a rare fibroepithelial neoplasm of the breast, poses a significant diagnostic challenge in breast pathology, as there are no generally accepted histological criteria or cutoffs to unambiguously differentiate PT variants (benign, borderline, malignant) and fibroadenomas (FA) of the breast. In recent years, genome-wide DNA methylation analysis has gained wide interest as an objective tool to distinguish all sorts of neoplasms based on their individual methylation signatures. For brain tumors, methylation-based classification already outperforms classification by conventional histology and has led to changes in the WHO tumor classification. Materials and Methods: We have so far analyzed fresh frozen as well as formalin-fixed, paraffin-embedded tissue samples of PT (n=31) and FA (n=2) on Illumina Infinium Methylation EPIC bead chips. The resulting data were preprocessed, normalized, mapped to the genome and converted into beta values. Top differentially methylated probes were determined by the calculation of standard deviations across the dataset. Such filtered sets of methylation beta values were then compared by a dimension reduction algorithm alongside TCGA methylome datasets as well as collections from GEO and the entire diagnostic database of our institute (n=14342). In parallel, the genome-wide copy number alterations were calculated from array data for each case. Results: In analogy to other tumor entities included in our reference cohort (brain tumors, sarcomas, carcinomas, melanomas), PT and FA of the breast show distinct DNA methylation patterns that contain a breast-specific signature as well as tumor-derived patterns. Their methylomes are distinct from breast adenocarcinoma as well as from healthy breast tissue. Two distinct groups within the PT/FA spectrum were identified so far: One group contains a high fraction of histologically malignant PT and is enriched for complex copy number alterations while the other group, also containing the currently two included fibroadenomas and, features less prominent to no copy number variants and a higher similarity to the overall normal breast tissue methylation signature. Conclusion: The distinct methylation signatures of the histological PT/FA spectrum will not only allow the diagnostic discrimination of PTs from histological mimics such as FA or carcinomas, but will also enable the distinction of benign, borderline and malignant PTs, thus paving the way to an optimized prognostic patient stratification and clinical management. Citation Format: Simone Muenst, Tatjana Vlajnic, Savas Deniz Soysal, Stefan Frank, Jürgen Hench. Distinct methylation and copy number alteration patterns in phyllodes tumors of the breast and its mimics [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-21-02.
Integrative -omics and HLA-ligandomics analysis to identify novel drug targets for ccRCC immunotherapy
Authors: Anna Reustle, Moreno Di Marco, Carolin Meyerhoff, Annika Nelde, Juliane S. Walz, Stefan Winter, Siahei Kandabarau, Florian Büttner, Mathias Haag, Linus Backert, Daniel J. Kowalewski, Steffen Rausch, Jörg Hennenlotter, Viktoria Stühler, Marcus Scharpf, Falko Fend, Arnulf Stenzl, Hans-Georg Rammensee, Jens Bedke, Stefan Stevanović, Matthias Schwab, Elke Schaeffeler
Journal: Genome Medicine (2020)

Abstract Background Clear cell renal cell carcinoma (ccRCC) is the dominant subtype of renal cancer. With currently available therapies, cure of advanced and metastatic ccRCC is achieved only in rare cases. Here, we developed a workflow integrating different - omics technologies to identify ccRCC-specific HLA-presented peptides as potential drug targets for ccRCC immunotherapy. Methods We analyzed HLA-presented peptides by MS-based ligandomics of 55 ccRCC tumors (cohort 1), paired non-tumor renal tissues, and 158 benign tissues from other organs. Pathways enriched in ccRCC compared to its cell type of origin were identified by transcriptome and gene set enrichment analyses in 51 tumor tissues of the same cohort. To retrieve a list of candidate targets with involvement in ccRCC pathogenesis, ccRCC-specific pathway genes were intersected with the source genes of tumor-exclusive peptides. The candidates were validated in an independent cohort from The Cancer Genome Atlas (TCGA KIRC, n = 452). DNA methylation (TCGA KIRC, n = 273), somatic mutations (TCGA KIRC, n = 392), and gene ontology (GO) and correlations with tumor metabolites (cohort 1, n = 30) and immune-oncological markers (cohort 1, n = 37) were analyzed to characterize regulatory and functional involvements. CD8 + T cell priming assays were used to identify immunogenic peptides. The candidate gene EGLN3 was functionally investigated in cell culture. Results A total of 34,226 HLA class I- and 19,325 class II-presented peptides were identified in ccRCC tissue, of which 443 class I and 203 class II peptides were ccRCC-specific and presented in ≥ 3 tumors. One hundred eighty-five of the 499 corresponding source genes were involved in pathways activated by ccRCC tumors. After validation in the independent cohort from TCGA, 113 final candidate genes remained. Candidates were involved in extracellular matrix organization, hypoxic signaling, immune processes, and others. Nine of the 12 peptides assessed by immunogenicity analysis were able to activate naïve CD8 + T cells, including peptides derived from EGLN3 . Functional analysis of EGLN3 revealed possible tumor-promoting functions. Conclusions Integration of HLA ligandomics, transcriptomics, genetic, and epigenetic data leads to the identification of novel functionally relevant therapeutic targets for ccRCC immunotherapy. Validation of the identified targets is recommended to expand the treatment landscape of ccRCC.
Abstract P2-15-13: A time-and-motion study of chemotherapy administration in metastatic breast cancer
Authors: Lee Schwartzberg, Debanjana Chatterjee, Russel Knoth, Sarah N Gibbs, K Hamzah Ahmed, Michael S Broder, Irina Yermilov
Journal: Cancer Research (2020)

Abstract Background: Ordering and delivering chemotherapy is complex, impacting patient and caregiver quality of life. Metastatic breast cancer (mBC) patients receive intravenous chemotherapy with variable administration times and patient satisfaction may differ by session length. We investigated common chemotherapy agents for mBC through a time and motion analysis. Methods: We conducted a prospective, observational time-and-motion study of adult females with mBC receiving ≥ 2nd-line eribulin, vinorelbine (VI), or gemcitabine (GC) at a large community oncology clinic. An observer documented times events occurred (Table). Patients completed a satisfaction survey adapted from Agency for Healthcare Research and Quality’s cancer care survey and the Cancer Therapy Satisfaction Questionnaire. Event times were compared using t-test. Spearman’s rank correlation was used to test correlations between time and satisfaction. Results: 17 patients (11 eribulin, 6 VI/GC) comprising 31 observations (20 eribulin, 11 VI/GC) were included in the preliminary analysis. Patients were 65 years on average, 71% white, and 94% post-menopausal; all were HER-2-. Mean years since mBC diagnosis was lower for eribulin than VI/GC patients (1.7 vs 5.0, p&amp;lt;0.009). Chemotherapy administration was shorter for eribulin patients (Table). 82% of patients were very satisfied with their cancer care experience; satisfaction did not correlate with event times. Conclusions: Eribulin administration time was significantly lower than VI/GC in mBC patients while maintaining similar satisfaction levels. These preliminary results demonstrate novel treatments for mBC can shorten treatment administration time while providing patient-centered, coordinated care. Table. Observation by event (mean minutes) All observationsEribulin Vinorelbine/ GemcitabineP value *&amp;lt;0.05Chair time (total time patient was in chair)7367840.174Chemotherapy ordered to chemotherapy end5449610.080Chemotherapy ordered to discharge6557740.111Chemotherapy arrived chair-side to chemotherapy end1510230.003*Chemotherapy arrived chair-side to discharge2620370.007*Chemotherapy administration (medication start to end)116200.001* Citation Format: Lee Schwartzberg, Debanjana Chatterjee, Russel Knoth, Sarah N Gibbs, K Hamzah Ahmed, Michael S Broder, Irina Yermilov. A time-and-motion study of chemotherapy administration in metastatic breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-15-13.
Rewilding Nod2 and Atg16l1 Mutant Mice Uncovers Genetic and Environmental Contributions to Microbial Responses and Immune Cell Composition
Authors: Jian-Da Lin, Joseph C. Devlin, Frank Yeung, Caroline McCauley, Jacqueline M. Leung, Ying-Han Chen, Alex Cronkite, Christina Hansen, Charlotte Drake-Dunn, Kelly V. Ruggles, Ken Cadwell, Andrea L. Graham, P’ng Loke
Journal: Cell Host & Microbe (2020)
Beta Cell Dedifferentiation Induced by IRE1α Deletion Prevents Type 1 Diabetes
Authors: Hugo Lee, Yong-Syu Lee, Quincy Harenda, Stefan Pietrzak, Hülya Zeynep Oktay, Sierra Schreiber, Yian Liao, Shreyash Sonthalia, Ashley E. Ciecko, Yi-Guang Chen, Sunduz Keles, Rupa Sridharan, Feyza Engin
Journal: Cell Metabolism (2020)
Multiple myeloma: 2020 update on diagnosis, risk‐stratification and management
Authors: S. Vincent Rajkumar
Journal: American Journal of Hematology (2020)

Multiple myeloma accounts for approximately 10% of hematologic malignancies.The diagnosis requires ≥10% clonal bone marrow plasma cells or a biopsy proven plasmacytoma plus evidence of one or more multiple myeloma defining events (MDE) namely CRAB (hypercalcemia, renal failure, anemia, or lytic bone lesions) features felt related to the plasma cell disorder, bone marrow clonal plasmacytosis ≥60%, serum involved/uninvolved free light chain (FLC) ratio ≥100 (provided involved FLC is ≥100 mg/L), or >1 focal lesion on magnetic resonance imaging (MRI).The presence of del(17p), t(4;14), t(14;16), t(14;20), gain 1q, or p53 mutation is considered high-risk multiple myeloma. Presence of any two high risk factors is considered double-hit myeloma; three or more high risk factors is triple-hit myeloma.In transplant eligible patients, induction therapy consists of bortezomib, lenalidomide, dexamethasone (VRd) given for approximately 3-4 cycles followed by autologous stem cell transplantation (ASCT). In high-risk patients, daratumumab, bortezomib, lenalidomide, dexamethasone (Dara-VRd) is an alternative to VRd. Selected standard risk patients can get additional cycles of induction, and delay transplant until first relapse. Patients not candidates for transplant are typically treated with VRd for approximately 8-12 cycles followed by lenalidomide; alternatively these patients can be treated with daratumumab, lenalidomide, dexamethasone (DRd).After ASCT, standard risk patients need lenalidomide maintenance, while bortezomib-based maintenance is needed for patients with high-risk myeloma.Most patients require a triplet regimen at relapse, with the choice of regimen varying with each successive relapse.
Albumin-biomineralized nanoparticles to synergize phototherapy and immunotherapy against melanoma
Authors: Yining Zhu, Jiao Xue, Wenfei Chen, Shuting Bai, Tao Zheng, Chunting He, Zhaofei Guo, Min Jiang, Guangsheng Du, Xun Sun
Journal: Journal of Controlled Release (2020)
Abstract C36: A roadmap for targeting cysteine dependency in a subset of pancreatic cancer
Authors: Zeribe C. Nwosu, Matthew H. Ward, Peter Sajjakulnukit, Li Zhang, Marina Pasca di Magliano, Costas A. Lyssiotis
Journal: Cancer Research (2019)

Abstract Cysteine is a crucial amino acid for glutathione biosynthesis, which is necessary for the maintenance of cellular antioxidant defense. Recent studies have shown that cysteine deprivation induces ferroptotic cell death in cancer cells, indicating an exploitable metabolic vulnerability for cancer therapy. However, the molecular variables that underpin cysteine dependency or can be selectively targeted to mimic cysteine deprivation are largely unknown. Here, we have studied cysteine dependency using over 20 pancreatic cancer cells (~35% of which are patient-derived), by measuring cell viability upon cystine withdrawal. In addition, we measured metabolite signatures by mass spectrometry, assessed genomic profile by bioinformatic analysis and qPCR, and also analyzed protein-level expression of cystine-glutamate antiporter SLC7A11 (xCT)—a known transporter for cystine uptake. We found that pancreatic cancer cells cluster at least into three groups, namely, cysteine-independent, moderately dependent, and highly dependent cells. The highly dependent group consistently showed low intracellular cysteine, methionine, and glutamine and a high level of intermediary metabolites of glycolytic pathway. This is accompanied by a downregulation of genes involved in apoptosis, lysosomal function, and the upregulation of cell cycle gene network as revealed by altered pathway enrichment. Further, while the cysteine-independent cells express high gene and protein levels of SLC7A11, which was further upregulated upon cysteine deprivation, the highly dependent cells expressed a very low level of SLC7A11 regardless of cysteine availability. Importantly, by analyzing the cysteine-dependent cell lines, we identified several metabolic genes that are upregulated in human pancreatic cancer and predict patient overall survival (e.g., HIF1A, LDHA, SLC16A1). In conclusion, we have uncovered differential cysteine dependency and the accompanying hallmarks in pancreatic cancer cells, thus providing impetus for targeting cysteine metabolism in a specific subset of pancreatic cancer. Citation Format: Zeribe C. Nwosu, Matthew H. Ward, Peter Sajjakulnukit, Li Zhang, Marina Pasca di Magliano, Costas A. Lyssiotis. A roadmap for targeting cysteine dependency in a subset of pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr C36.
Covid-19: Mercedes F1 to provide breathing aid as alternative to ventilator
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Covid-19: Mercedes F1 to provide breathing aid as alternative to ventilator MahaseThe BMJ Mercedes F1 will produce continuous positive airway pressure (CPAP) machines for the NHS to use on covid-19 patients with serious lung infections, as a less invasive alternative to ventilators.
Brain-specific repression of AMPKα1 alleviates pathophysiology in Alzheimer’s model mice
Authors: Helena R. Zimmermann, Wenzhong Yang, Nicole P. Kasica, Xueyan Zhou, Xin Wang, Brenna C. Beckelman, Jingyun Lee, Cristina M. Furdui, C. Dirk Keene, Tao Ma
Journal: Journal of Clinical Investigation (2020)

AMPK is a key regulator at the molecular level for maintaining energy metabolism homeostasis. Mammalian AMPK is a heterotrimeric complex, and its catalytic α subunit exists in 2 isoforms: AMPKα1 and AMPKα2. Recent studies suggest a role of AMPKα overactivation in Alzheimer's disease-associated (AD-associated) synaptic failure. However, whether AD-associated dementia can be improved by targeting AMPK remains unclear, and roles of AMPKα isoforms in AD pathophysiology are not understood. Here, we showed distinct disruption of hippocampal AMPKα isoform expression patterns in postmortem human AD patients and AD model mice. We further investigated the effects of brain- and isoform-specific AMPKα repression on AD pathophysiology. We found that repression of AMPKα1 alleviated cognitive deficits and synaptic failure displayed in 2 separate lines of AD model mice. In contrast, AMPKα2 suppression did not alter AD pathophysiology. Using unbiased mass spectrometry-based proteomics analysis, we identified distinct patterns of protein expression associated with specific AMPKα isoform suppression in AD model mice. Further, AD-associated hyperphosphorylation of eukaryotic elongation factor 2 (eEF2) was blunted with selective AMPKα1 inhibition. Our findings reveal isoform-specific roles of AMPKα in AD pathophysiology, thus providing insights into potential therapeutic strategies for AD and related dementia syndromes.
Low-Grade Versus High-Grade Glioma… That Is the Question. 18F-Fluorocholine PET in the Detection of Anaplastic Focus
Authors: Ana María García Vicente, José Manuel Cordero García, Carlos López Menéndez, Jose María Borrás Moreno, Angel Soriano Castrejón
Journal: Clinical Nuclear Medicine (2020)

Gliomas are characterized by intratumoral histological heterogeneity, coexisting foci of low and high grade. First, in low-grade gliomas, neoangiogenesis has not yet developed and cellularity is low, so alterations on perfusion MRI may not be present. Second, a non-negligible number of high-grade gliomas show none, patchy, or weak contrast enhancement on MRI, so they can be misdiagnosed as low-grade glioma, preventing their correct management. We present 4 cases of patients in which F-fluorocholine PET defined the anaplastic tumor component and therefore the tumor aggressiveness, solving the limitations of MRI.
Aspartate transaminase to platelet ratio index (APRI) and albumin-bilirubin grade (ALBI) predict postoperative morbidity following hepatectomy for hepatocellular carcinoma - A multicenter cohort study
Authors: Li-yang Sun, Lei Liang, Hao Xing, Chao Li, Ming-da Wang, Ya-hao Zhou, Wei-min Gu, Ting-hao Chen, Yong-yi Zeng, Wan Yee Lau, Feng Shen, Tian Yang
Journal: International Journal of Surgery (2020)
Molecular characterization of SARS-CoV-2 from the first case of COVID-19 in Italy
Authors: M.R. Capobianchi, M. Rueca, F. Messina, E. Giombini, F. Carletti, F. Colavita, C. Castilletti, E. Lalle, L. Bordi, F. Vairo, E. Nicastri, G. Ippolito, C.E.M. Gruber, B. Bartolini
Journal: Clinical Microbiology and Infection (2020)