tbuckley/cabot-search huggingface dataset:
StrainGE: a toolkit to track and characterize low-abundance strains in complex microbial communities
Authors: Lucas R. van Dijk, Bruce J. Walker, Timothy J. Straub, Colin J. Worby, Alexandra Grote, Henry L. Schreiber, Christine Anyansi, Amy J. Pickering, Scott J. Hultgren, Abigail L. Manson, Thomas Abeel, Ashlee M. Earl
Journal: Genome biology (2022)

Abstract Human-associated microbial communities comprise not only complex mixtures of bacterial species, but also mixtures of conspecific strains, the implications of which are mostly unknown since strain level dynamics are underexplored due to the difficulties of studying them. We introduce the Strain Genome Explorer (StrainGE) toolkit, which deconvolves strain mixtures and characterizes component strains at the nucleotide level from short-read metagenomic sequencing with higher sensitivity and resolution than other tools. StrainGE is able to identify strains at 0.1x coverage and detect variants for multiple conspecific strains within a sample from coverages as low as 0.5x.
Digital health tools for the passive monitoring of depression: a systematic review of methods
Authors: Valeria De Angel, Serena Lewis, Katie White, Carolin Oetzmann, Daniel Leightley, Emanuela Oprea, Grace Lavelle, Faith Matcham, Alice Pace, David C. Mohr, Richard Dobson, Matthew Hotopf
Journal: npj Digital Medicine (2022)

The use of digital tools to measure physiological and behavioural variables of potential relevance to mental health is a growing field sitting at the intersection between computer science, engineering, and clinical science. We summarised the literature on remote measuring technologies, mapping methodological challenges and threats to reproducibility, and identified leading digital signals for depression. Medical and computer science databases were searched between January 2007 and November 2019. Published studies linking depression and objective behavioural data obtained from smartphone and wearable device sensors in adults with unipolar depression and healthy subjects were included. A descriptive approach was taken to synthesise study methodologies. We included 51 studies and found threats to reproducibility and transparency arising from failure to provide comprehensive descriptions of recruitment strategies, sample information, feature construction and the determination and handling of missing data. The literature is characterised by small sample sizes, short follow-up duration and great variability in the quality of reporting, limiting the interpretability of pooled results. Bivariate analyses show consistency in statistically significant associations between depression and digital features from sleep, physical activity, location, and phone use data. Machine learning models found the predictive value of aggregated features. Given the pitfalls in the combined literature, these results should be taken purely as a starting point for hypothesis generation. Since this research is ultimately aimed at informing clinical practice, we recommend improvements in reporting standards including consideration of generalisability and reproducibility, such as wider diversity of samples, thorough reporting methodology and the reporting of potential bias in studies with numerous features.
Abstract P2-12-19: Platinum is essential in neoadjuvant treatment of triple negative breast cancer: A network meta-analysis
Authors: Junjie Li, Li Chen, Wei Tan, Fang Qi, Yang Zhang, Zhonghua Wang, Zhimin Shao
Journal: Cancer Research (2022)

Abstract Background: Due to the heterogeneity of triple negative breast cancer (TNBC) and variety of neoadjuvant regimen, the best way to provide optimal neoadjuvant regimen in early-stage TNBC is still a challenge. However, the preferred regimen, especially when combining target therapy such as bevacizumab, Poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors (PARPi), and PD-1/PD-L1 inhibitor, is still not clear. Methods: Medline, EMBASE, Cochrane Library, and Web of Science were searched in May 2020 to identify randomized controlled trials (RCTs). We conducted a fixed-effect network meta-analysis (NMA) with a Bayesian framework to assess the efficacy and safety of different neoadjuvant regimens for patients with early or locally advanced TNBC. (Registration: PROSPERO CRD42020223012). Results: A total of 35 RCTs involving 8424 participants were included, of which, 22 RCTs with 5203 patients were included in this NMA focusing on pathologic complete response (pCR). Compared to anthracycline-taxane based regimen (AT), an improvement in pCR was observed for anthracycline-taxane based combined platinum (ATP) (odds ratio [OR]=2.04, 95% credible interval [CrI]: 1.69, 2.48), TCb (T= docetaxel; Cb= carboplatin; OR=2.16, 95%CrI: 1.20, 3.91). Combining target therapy (including bevacizumab [Bev], veliparib, atezolizumab, or pembrolizumab) with AT or ATP also improved pCRs. Eleven RCTs reported serious adverse events (SAEs), and five RCTs were included in NMA. TCb was associated with less serious adverse events than AT. However, ATP, AT+Bev, ATP+Bev, ATP+Veliparib and ATP+Pembro were associated with more serious AEs than AT. Conclusions: Platinum-based neoadjuvant regimens increased pCRs in TNBC patients, among which TCb was preferred with less SAEs. Platinum-based regimens should also be considered a preferred option when combining target therapy such as Bev, PARPi, and PD-1/PD-L1 inhibitor. Citation Format: Junjie Li, Li Chen, Wei Tan, Fang Qi, Yang Zhang, Zhonghua Wang, Zhimin Shao. Platinum is essential in neoadjuvant treatment of triple negative breast cancer: A network meta-analysis [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-12-19.
CHRONIC KIDNEY DISEASE AND PERCUTANEOUS CORONARY INTERVENTION: IMPACT OF AGE AND ACUITY ON IN-HOSPITAL OUTCOMES AND BLEEDING COMPLICATIONS
Authors: Tia Bimal, Md Bhuiyan, Umair Ansari, Joanna Fishbein, Puneet Gandotra, Samy Selim, Lawrence Y.C. Ong, Luis Gruberg
Journal: Journal of the American College of Cardiology (2022)
OUTCOMES OF MYOCARDIAL INFARCTION WITH NONOBSTRUCTIVE CORONARY ARTERIES (MINOCA) PATIENTS PRESENTING WITH ST-SEGMENT ELEVATION
Authors: Mehmet Yildiz, Santiago Garcia, Ananya Shah, Brynn Okeson, Jenny Chambers, Lucas Volpenhein, Rebekah Lantz, Dalia Aziz, Ross Garberich, Heather Rohm, Frank V. Aguirre, Scott W. Sharkey, Timothy D. Henry, Odayme Quesada
Journal: Journal of the American College of Cardiology (2022)
Reply to T. Olivier et al
Authors: Jedd D. Wolchok, Harriet Kluger, Federico Campigotto, James Larkin, F. Stephen Hodi
Journal: Journal of Clinical Oncology (2022)

I am a co-inventor on an issued patent for DNA vaccines for treatment of cancer in companion animals, I am a co-inventor on a patent for use of oncolytic Newcastle Disease virus, I am a coinventor and receive royalties for a blood test for monitoring myeloid derived suppressor cells, I am co-inventor and receive royalties for a patent for immune modulating antibodies, I am a co-inventor on a patent for CAR 1 T cells targeting differentiation antigens as means to treat cancer, and I am
TraSig: inferring cell-cell interactions from pseudotime ordering of scRNA-Seq data
Authors: Dongshunyi Li, Jeremy J. Velazquez, Jun Ding, Joshua Hislop, Mo R. Ebrahimkhani, Ziv Bar-Joseph
Journal: Genome biology (2022)

A major advantage of single cell RNA-sequencing (scRNA-Seq) data is the ability to reconstruct continuous ordering and trajectories for cells. Here we present TraSig, a computational method for improving the inference of cell-cell interactions in scRNA-Seq studies that utilizes the dynamic information to identify significant ligand-receptor pairs with similar trajectories, which in turn are used to score interacting cell clusters. We applied TraSig to several scRNA-Seq datasets and obtained unique predictions that improve upon those identified by prior methods. Functional experiments validate the ability of TraSig to identify novel signaling interactions that impact vascular development in liver organoids.Software https://github.com/doraadong/TraSig .
Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial
Authors: Sattva S. Neelapu, Michael Dickinson, Javier Munoz, Matthew L. Ulrickson, Catherine Thieblemont, Olalekan O. Oluwole, Alex F. Herrera, Chaitra S. Ujjani, Yi Lin, Peter A. Riedell, Natasha Kekre, Sven de Vos, Christine Lui, Francesca Milletti, Jinghui Dong, Hairong Xu, Julio C. Chavez
Journal: Nature Medicine (2022)

High-risk large B-cell lymphoma (LBCL) has poor outcomes with standard first-line chemoimmunotherapy. In the phase 2, multicenter, single-arm ZUMA-12 study (ClinicalTrials.gov NCT03761056) we evaluated axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, as part of first-line treatment in 40 patients with high-risk LBCL. This trial has completed accrual. The primary outcome was complete response rate (CRR). Secondary outcomes were objective response rate (ORR), duration of response (DOR), event-free survival (EFS), progression-free survival (PFS), overall survival (OS), assessment of safety, central nervous system (CNS) relapse and blood levels of CAR T cells and cytokines. The primary endpoint in efficacy-evaluable patients (n = 37) was met, with 78% CRR (95% confidence interval (CI), 62–90) and 89% ORR (95% CI, 75–97). As of 17 May 2021 (median follow-up, 15.9 months), 73% of patients remained in objective response; median DOR, EFS and PFS were not reached. Grade ≥3 cytokine release syndrome (CRS) and neurologic events occurred in three patients (8%) and nine patients (23%), respectively. There were no treatment-related grade 5 events. Robust CAR T-cell expansion occurred in all patients with a median time to peak of 8 days. We conclude that axi-cel is highly effective as part of first-line therapy for high-risk LBCL, with a manageable safety profile. In a phase 2 trial, first-line treatment with axicabtagene ciloleucel, an autologous CD19-targeting CAR T-cell therapy, exhibited a high complete response rate and a manageable safety profile in adults with high-risk large B-cell lymphoma.
BPI22-022: Real World Adherence to Biomarker Testing Guidelines That Inform First-Line Treatment Decisions for Patients Newly Diagnosed With Metastatic Non-Small Cell Lung Cancer in the Community Setting
Authors: Amy M. Pasmann, William E. Nibley, Scott D. Goldfarb, Veena Shetty, Jon M. Apple, Anne Shah
Journal: Journal of the National Comprehensive Cancer Network (2022)

"BPI22-022: Real World Adherence to Biomarker Testing Guidelines That Inform First-Line Treatment Decisions for Patients Newly Diagnosed With Metastatic Non-Small Cell Lung Cancer in the Community Setting" published on 31 Mar 2022 by National Comprehensive Cancer Network.
Fate mapping and scRNA sequencing reveal origin and diversity of lymph node stromal precursors
Authors: Elisa Lenti, Luca Genovese, Silvia Bianchessi, Aurora Maurizio, Simona Baghai Sain, Alessia di Lillo, Greta Mattavelli, Itamar Harel, Francesca Bernassola, Thomas Hehlgans, Klaus Pfeffer, Mariacristina Crosti, Sergio Abrignani, Sylvia M. Evans, Giovanni Sitia, Nuno Guimarães-Camboa, Vincenzo Russo, Serge A. van de Pavert, Jose Manuel Garcia-Manteiga, Andrea Brendolan
Journal: Immunity (2022)
Endoscopic retrograde appendicitis therapy: a starting point for a change of perspective in treating acute appendicitis (and beyond)
Authors: Mauro Podda
Journal: Endoscopy (2022)

As a surgeon who grew up with the dogma that every acute appendicitis demands a surgical treatment with appendectomy, I could never have imagined myself re-evaluating the role of nonoperative treatment with antibiotics and other preserving strategies for acute appendicitis. However, as the great philosopher Arthur Schopenhauer said "There are three steps in the revelation of any truth: in the first, it is ridiculed; in the second, resisted; in the third, it is considered self-evident." After passionately investigating the role of antibiotics as the sole treatment for uncomplicated acute appendicitis, I confess I am currently in the second step in the revelation of the truth, but very close to the third.
IMPACT OF CHRONIC THROMBOCYTOPENIA ON CLINICAL OUTCOMES AFTER TAVR: INSIGHTS FROM THE BRAVO-3 RANDOMIZED TRIAL
Authors: Daniel Feldman, Davide Cao, Victor Razuk, Johny Nicolas, Christian Hengstenberg, Zhongie Zhang, Samantha Sartori, Frans Beerkens, Carlo Andrea Pivato, Mauro Chiarito, Davis B. Jones, Mohan Satish, Anastasios Roumeliotis, David Power, Anton Camaj, Raban V. Jeger, Roberto Violini, Markus Ferrari, Roxana Mehran, George D. Dangas
Journal: Journal of the American College of Cardiology (2022)
Abstract ES8-3: Refining axillary management after neoadjuvant chemotherapy - what does the evidence support
Authors: P Mamounas
Journal: Cancer Research (2022)

Abstract The surgical management of the axilla in patients with operable breast cancer has undergone significant evolution over the past 25 years. Axillary lymph node dissection (ALND), the undisputed standard since the end of the 19th century, has largely been replaced by sentinel lymph node biopsy (SLNB) in most patients with clinically negative axilla with considerable reduction in axillary morbidity. Neoadjuvant chemotherapy (NAC) has been increasingly used in early-stage breast cancer, particularly in patients with triple-negative and HER-2 neu positive tumors. Rates of sterilization of involved axillary lymph nodes with NAC in appropriately selected patients have been steadily increasing with the adoption of more effective NAC regimens. Adoption of SLNB after NAC has lagged behind that of upfront SLNB. Recent data support the feasibility and accuracy of the procedure after NAC in patients who present with clinically negative axilla. Although the accuracy of SLNB is lower after NAC in patients who present with documented involvement of the axilla, identification and removal of the previously biopsied axillary lymph node(s) in addition to performing SLNB (“targeted axillary dissection”) greatly improves the accuracy to levels equivalent to those with upfront SLNB. Citation Format: P Mamounas. Refining axillary management after neoadjuvant chemotherapy - what does the evidence support [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr ES8-3.
Image quality assessment for machine learning tasks using meta-reinforcement learning
Authors: Shaheer U. Saeed, Yunguan Fu, Vasilis Stavrinides, Zachary M.C. Baum, Qianye Yang, Mirabela Rusu, Richard E. Fan, Geoffrey A. Sonn, J. Alison Noble, Dean C. Barratt, Yipeng Hu
Journal: Medical Image Analysis (2022)

In this paper, we consider image quality assessment (IQA) as a measure of how images are amenable with respect to a given downstream task, or task amenability. When the task is performed using machine learning algorithms, such as a neural-network-based task predictor for image classification or segmentation, the performance of the task predictor provides an objective estimate of task amenability. In this work, we use an IQA controller to predict the task amenability which, itself being parameterised by neural networks, can be trained simultaneously with the task predictor. We further develop a meta-reinforcement learning framework to improve the adaptability for both IQA controllers and task predictors, such that they can be fine-tuned efficiently on new datasets or meta-tasks. We demonstrate the efficacy of the proposed task-specific, adaptable IQA approach, using two clinical applications for ultrasound-guided prostate intervention and pneumonia detection on X-ray images.
Phase 2 trial of T-cell activation using MVI-816 and pembrolizumab in patients with metastatic, castration-resistant prostate cancer (mCRPC)
Authors: Douglas G McNeel, Jens C Eickhoff, Ellen Wargowski, Laura E Johnson, Christos E Kyriakopoulos, Hamid Emamekhoo, Joshua M Lang, Mary Jane Brennan, Glenn Liu
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background We previously reported a trial using a DNA vaccine encoding prostatic acid phosphatase (MVI-816, pTVG-HP), given over 12 weeks concurrently or sequentially with pembrolizumab, in patients with mCRPC. We report the final analysis of this trial following two additional treatment arms in which patients with mCRPC continued concurrent treatment until progression. Materials and methods Patients with mCRPC were treated with MVI-816 and pembrolizumab every 3 weeks (arm 3, n=20) or MVI-816 every 2 weeks and pembrolizumab every 4 weeks (arm 4, n=20). The primary objectives were safety, 6-month progression-free survival (PFS), median time to radiographic progression, and objective response rates. Secondary objectives included immunological evaluations. Results In 25 patients with measurable disease, there were no complete response and one confirmed partial response in a patient who subsequently found to have an MSI hi tumor. 4/40 patients (10%) had a prostate-specific antigen decline &gt;50%. The estimated overall radiographic PFS rate at 6 months was 47.2% (44.4% arm 3, 61.5% arm 4). Accounting for all off-study events, overall median time on treatment was 5.6 months (95% CI: 5.4 to 10.8 months), 5.6 months for arm 3 and 8.1 months for arm 4 (p=0.64). Thirty-two per cent of patients remained on trial beyond 6 months without progression. Median overall survival was 22.9 (95% CI: 16.2 to 25.6) months. One grade 4 event (hyperglycemia) was observed. Immune-related adverse events (irAEs) &gt;grade 1 were observed in 42% of patients overall. Interferon-γ and/or granzyme B immune response to prostatic acid phosphatase was detected in 2/20 patients in arm 3 and 6/20 patients in arm 4. Plasma cytokines associated with immune activation and CD8+ T-cell recruitment were augmented at weeks 6 and 12. The development of irAE was significantly associated with a prolonged time on treatment (HR=0.42, p=0.003). Baseline DNA homologous recombination repair mutations were not associated with longer time to progression. Conclusions Findings here demonstrate that combining programmed cell death 1 blockade with MVI-816 is safe, can augment tumor-specific T cells, and can result in a favorable 6-month disease control rate. Correlative studies suggest T-cell activation by vaccination is critical to the mechanism of action of this combination. Future randomized clinical trials are needed to validate these findings. Trial registration number NCT02499835 .
SEX- AND RACE-SPECIFIC BURDEN OF AORTIC VALVE CALCIFICATION AMONG ADULTS ≥75 YEARS - THE ATHEROSCLEROSIS RISK IN COMMUNITIES STUDY
Authors: Ellen Boakye, Olufunmilayo H. Obisesan, Albert D. Osei, Zeina Dardari, Omar Dzaye, Ngozi Osuji, Frances M. Wang, Yasuyuki Honda, John Jeffrey Carr, Candace Howard-Claudio, Lynne Wagenknecht, Suma H. Konety, Josef Coresh, Kunihiro Matsushita, Michael Blaha, Seamus P. Whelton
Journal: Journal of the American College of Cardiology (2022)
COMBINED THERAPY WITH SODIUM-GLUCOSE COTRANSPORTER-2 INHIBITORS (SGLT2I) AND GLUCAGON-LIKE PEPTIDE-1 RECEPTOR AGONISTS (GLP1-RA)—TOLERABILITY AND CLINICAL IMPACT: THE INTERMOUNTAIN HEALTHCARE REAL WORLD EXPERIENCE
Authors: Viet T. Le, Ana Cristina Perez-Moreno, Peter Calderone, Josh Epstein, J. Brent Muhlestein, Kirk U. Knowlton, Jeffrey L. Anderson
Journal: Journal of the American College of Cardiology (2022)
THE DYEVERT CONTRAST REDUCTION SYSTEM AND CONTRAST INDUCED NEPHROPATHY: IS IT ANY BETTER?
Authors: Olusola Olubowale, Ebad Ur Rahman, Kelechukwu U. Okoro, Hari Vishal Lakhani, Ebubechukwu Ezeh, Gregg C. Fonarow, Mehiar El-Hamdani
Journal: Journal of the American College of Cardiology (2022)
30-DAY READMISSION RATE FOR DIASTOLIC HEART FAILURE IN PATIENT WITH TYPE 2 DIABETES AND ITS ECONOMIC BURDEN ON HEALTHCARE
Authors: Michael A. Fatuyi, Leanne Pereira, Vivek Sharma, Awfa Zain Elabidin, Vahid Namdarizandi, Leonid Khokhlov, Mubarak H. Yusuf, Asimul H. Ansari, Kamal Shemisa
Journal: Journal of the American College of Cardiology (2022)
The chromatin organization of a chlorarachniophyte nucleomorph genome
Authors: Georgi K. Marinov, Xinyi Chen, Tong Wu, Chuan He, Arthur R. Grossman, Anshul Kundaje, William James Greenleaf
Journal: Genome biology (2022)

Abstract Background Nucleomorphs are remnants of secondary endosymbiotic events between two eukaryote cells wherein the endosymbiont has retained its eukaryotic nucleus. Nucleomorphs have evolved at least twice independently, in chlorarachniophytes and cryptophytes, yet they have converged on a remarkably similar genomic architecture, characterized by the most extreme compression and miniaturization among all known eukaryotic genomes. Previous computational studies have suggested that nucleomorph chromatin likely exhibits a number of divergent features. Results In this work, we provide the first maps of open chromatin, active transcription, and three-dimensional organization for the nucleomorph genome of the chlorarachniophyte Bigelowiella natans . We find that the B. natans nucleomorph genome exists in a highly accessible state, akin to that of ribosomal DNA in some other eukaryotes, and that it is highly transcribed over its entire length, with few signs of polymerase pausing at transcription start sites (TSSs). At the same time, most nucleomorph TSSs show very strong nucleosome positioning. Chromosome conformation (Hi-C) maps reveal that nucleomorph chromosomes interact with one other at their telomeric regions and show the relative contact frequencies between the multiple genomic compartments of distinct origin that B. natans cells contain. Conclusions We provide the first study of a nucleomorph genome using modern functional genomic tools, and derive numerous novel insights into the physical and functional organization of these unique genomes.
BCL-XL PROTAC degrader DT2216 synergizes with sotorasib in preclinical models of KRASG12C-mutated cancers
Authors: Sajid Khan, Janet Wiegand, Peiyi Zhang, Wanyi Hu, Dinesh Thummuri, Vivekananda Budamagunta, Nan Hua, Lingtao Jin, Carmen J. Allegra, Scott E. Kopetz, Maria Zajac-Kaye, Frederic J. Kaye, Guangrong Zheng, Daohong Zhou
Journal: Journal of Hematology & Oncology (2022)

Abstract KRAS mutations are the most common oncogenic drivers. Sotorasib (AMG510), a covalent inhibitor of KRAS G12C , was recently approved for the treatment of KRAS G12C -mutated non-small cell lung cancer (NSCLC). However, the efficacy of sotorasib and other KRAS G12C inhibitors is limited by intrinsic resistance in colorectal cancer (CRC) and by the rapid emergence of acquired resistance in all treated tumors. Therefore, there is an urgent need to develop novel combination therapies to overcome sotorasib resistance and to maximize its efficacy. We assessed the effect of sotorasib alone or in combination with DT2216 (a clinical-stage BCL-X L proteolysis targeting chimera [PROTAC]) on KRAS G12C -mutated NSCLC, CRC and pancreatic cancer (PC) cell lines using MTS cell viability, colony formation and Annexin-V/PI apoptosis assays. Furthermore, the therapeutic efficacy of sotorasib alone and in combination with DT2216 was evaluated in vivo using different tumor xenograft models. We observed heterogeneous responses to sotorasib alone, whereas its combination with DT2216 strongly inhibited viability of KRAS G12C tumor cell lines that partially responded to sotorasib treatment. Mechanistically, sotorasib treatment led to stabilization of BIM and co-treatment with DT2216 inhibited sotorasib-induced BCL-X L /BIM interaction leading to enhanced apoptosis in KRAS G12C tumor cell lines. Furthermore, DT2216 co-treatment significantly improved the antitumor efficacy of sotorasib in vivo. Collectively, our findings suggest that due to cytostatic activity, the efficacy of sotorasib is limited, and therefore, its combination with a pro-apoptotic agent, i.e., DT2216, shows synergistic responses and can potentially overcome resistance.