tbuckley/cabot-search huggingface dataset:
Trycycler: consensus long-read assemblies for bacterial genomes
Authors: Ryan R. Wick, Louise M. Judd, Louise T. Cerdeira, Jane Hawkey, Guillaume Méric, Ben Vezina, Kelly L. Wyres, Kathryn E. Holt
Journal: Genome biology (2021)

Abstract While long-read sequencing allows for the complete assembly of bacterial genomes, long-read assemblies contain a variety of errors. Here, we present Trycycler, a tool which produces a consensus assembly from multiple input assemblies of the same genome. Benchmarking showed that Trycycler assemblies contained fewer errors than assemblies constructed with a single tool. Post-assembly polishing further reduced errors and Trycycler+polishing assemblies were the most accurate genomes in our study. As Trycycler requires manual intervention, its output is not deterministic. However, we demonstrated that multiple users converge on similar assemblies that are consistently more accurate than those produced by automated assembly tools.
PRINCESS: comprehensive detection of haplotype resolved SNVs, SVs, and methylation
Authors: Medhat Mahmoud, Harshavardhan Doddapaneni, Winston Timp, Fritz J. Sedlazeck
Journal: Genome biology (2021)

Long-read sequencing has been shown to have advantages in structural variation (SV) detection and methylation calling. Many studies focus either on SV, methylation, or phasing of SNV; however, only the combination of variants provides a comprehensive insight into the sample and thus enables novel findings in biology or medicine. PRINCESS is a structured workflow that takes raw sequence reads and generates a fully phased SNV, SV, and methylation call set within a few hours. PRINCESS achieves high accuracy and long phasing even on low coverage datasets and can resolve repetitive, complex medical relevant genes that often escape detection. PRINCESS is publicly available at https://github.com/MeHelmy/princess under the MIT license.
P-139 A phase 2 multicohort study (LEAP-005) of lenvatinib plus pembrolizumab in patients with previously treated selected solid tumors: Pancreatic cancer cohort
Authors: H. Chung, L. Villanueva, D. Graham, E. Saada-Bouzid, R. Ghori, P. Kubiak, B. Gumuscu, N. Lerman, C. Gomez-Roca
Journal: Annals of Oncology (2021)
New Treatment Approved for Adults and Children With Pompe Disease
Authors: Bridget M. Kuehn
Journal: JAMA (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Pragmatic Precision Psychiatry—A New Direction for Optimizing Treatment Selection
Authors: Ronald C. Kessler, Alex Luedtke
Journal: JAMA Psychiatry (2021)

Clinical trials have identified numerous prescriptive predictors of mental disorder treatment response, ie, predictors of which treatments are best for which patients. However, none of these prescriptive predictors is strong enough alone to guide precision treatment planning. This has prompted growing interest in developing precision treatment rules (PTRs) that combine information across multiple prescriptive predictors, but this work has been much less successful in psychiatry than some other areas of medicine. Study designs and analysis schemes used in research on PTR development in other areas of medicine are reviewed, key challenges for implementing similar studies of mental disorders are highlighted, and recent methodological advances to address these challenges are described here.Discovering prescriptive predictors requires large samples. Three approaches have been used in other areas of medicine to do this: conduct very large randomized clinical trials, pool individual-level results across multiple smaller randomized clinical trials, and develop preliminary PTRs in large observational treatment samples that are then tested in smaller randomized clinical trials. The third approach is most feasible for research on mental disorders. This approach requires working with large real-world observational electronic health record databases; carefully selecting samples to emulate trials; extracting information about prescriptive predictors from electronic health records along with other inexpensive data augmentation strategies; estimating preliminary PTRs in the observational data using appropriate methods; implementing pragmatic trials to validate the preliminary PTRs; and iterating between subsequent observational studies and quality improvement pragmatic trials to refine and expand the PTRs. New statistical methods exist to address the methodological challenges of implementing this approach.Advances in pragmatic precision psychiatry will require moving beyond the current focus on randomized clinical trials and adopting an iterative discovery-confirmation process that integrates observational and experimental studies in real-world clinical populations.
Treatment-Resistant Depression—Resistant to Placebos as Well?
Authors: Cristina Cusin, Luana Colloca
Journal: JAMA Network Open (2021)

Brett D. M. Jones, MD, MSc; Lais B. Razza, BSc; Cory R. Weissman, MD; Jewel Karbi, MD; Tya Vine, HBSc; Louise S. Mulsant, BASc; Andre R. Brunoni, MD, PhD; M. Ishrat Husain, MBBS, MD; Benoit H. Mulsant, MD, MSc; Daniel M. Blumberger, MD, MSc; Zafiris J. Daskalakis, MD, PhD
OS05.9.A Short-term fasting in glioma patients - Analysis of diet diaries and metabolic parameters of the ERGO2 trial
Authors: M Voss, K J Wenger, N von Mettenheim, J Bojunga, M Vetter, B Diehl, R Gerlach, M W Ronellenfitsch, K Franz, P N Harter, E Hattingen, J P Steinbach, C Rödel, J Rieger
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND The prospective, randomized ERGO2 trial investigated the effect of fasting / calorie restricted ketogenic diet (KD-IF) on re-irradiation for recurrent brain tumors (Clinicaltrials.gov number: NCT01754350). The study did not meet its primary endpoint of improved progression-free survival in comparison to a standard diet (SD). We here report the results of the quality of life questionnaire, neurocognition testing, detailed analysis of the diet diaries and the alterations of metabolic parameters. MATERIAL AND METHODS 50 Patients were randomized 1:1 to re-irradiation combined with either SD or KD-IF. The KD-IF schedule included 3 days of ketogenic diet (KD: 21–23 kcal/kg/d, carbohydrate intake limited to 50 g/d), followed by 3 days of fasting and again 3 days of KD. Follow-up included examination of cognition, quality of life and serum samples. RESULTS The 20 patients who completed KD-IF met the prespecified goals for calorie and carbohydrate restriction. In these, a decrease in leptin and insulin and an increase in uric acid was observed. The SD group had a lower calorie intake of 21 kcal/kg/d than the expected 30 kcal/kg/d. Neither quality of life nor cognition were affected by the diet. Low glucose emerged as a significant prognostic parameter in a best responder analysis. CONCLUSION The strict caloric goals of the ERGO2 trial could be achieved by patients with recurrent brain tumor. The unexpected lower calorie intake of the SD group might have hampered the interpretation of the trial. However, the short diet schedule already led to significant metabolic alterations, suggesting that short-term dietary interventions might be therapeutically useful, possibly combined with other modalities.
Past, Present, and Future of Radiation-Induced Cardiotoxicity: Refinements in Targeting, Surveillance, and Risk Stratification
Authors: Carmen Bergom, Julie A. Bradley, Andrea K. Ng, Pamela Samson, Clifford Robinson, Juan Lopez-Mattei, Joshua D. Mitchell
Journal: JACC CardioOncology (2021)

Radiation therapy is an important component of cancer therapy for many malignancies. With improvements in cardiac-sparing techniques, radiation-induced cardiac dysfunction has decreased but remains a continued concern. In this review, we provide an overview of the evolution of radiotherapy techniques in thoracic cancers and associated reductions in cardiac risk. We also highlight data demonstrating that in some cases radiation doses to specific cardiac substructures correlate with cardiac toxicities and/or survival beyond mean heart dose alone. Advanced cardiac imaging, cardiovascular risk assessment, and potentially even biomarkers can help guide post-radiotherapy patient care. In addition, treatment of ventricular arrhythmias with the use of ablative radiotherapy may inform knowledge of radiation-induced cardiac dysfunction. Future efforts should explore further personalization of radiotherapy to minimize cardiac dysfunction by coupling knowledge derived from enhanced dosimetry to cardiac substructures, post-radiation regional dysfunction seen on advanced cardiac imaging, and more complete cardiac toxicity data.
Next-generation prebiotic promotes selective growth of bifidobacteria, suppressing <i>Clostridioides difficile</i>
Authors: Rika Hirano, Mikiyasu Sakanaka, Kazuto Yoshimi, Naohisa Sugimoto, Syogo Eguchi, Yuko Yamauchi, Misaki Nara, Shingo Maeda, Yuta Ami, Aina Gotoh, Takane Katayama, Noriho Iida, Tamotsu Kato, Hiroshi Ohno, Satoru Fukiya, Atsushi Yokota, Mamoru Nishimoto, Motomitsu Kitaoka, Hiroyuki Nakai, Shin Kurihara
Journal: Gut Microbes (2021)

Certain existing prebiotics meant to facilitate the growth of beneficial bacteria in the intestine also promote the growth of other prominent bacteria. Therefore, the growth-promoting effects of β-galactosides on intestinal bacteria were analyzed. Galactosyl-β1,4-l-rhamnose (Gal-β1,4-Rha) selectively promoted the growth of Bifidobacterium. Bifidobacterium longum subsp. longum 105-A (JCM 31944) has multiple solute-binding proteins belonging to ATP-binding cassette transporters for sugars. Each strain in the library of 11 B. longum subsp. longum mutants, in which each gene of the solute-binding protein was disrupted, was cultured in a medium containing Gal-β1,4-Rha as the sole carbon source, and only the BL105A_0502 gene-disruption mutant showed delayed and reduced growth compared to the wild-type strain. BL105A_0502 homolog is highly conserved in bifidobacteria. In a Gal-β1,4-Rha-containing medium, Bifidobacterium longum subsp. infantis JCM 1222T, which possesses BLIJ_2090, a homologous protein to BL105A_0502, suppressed the growth of enteric pathogen Clostridioides difficile, whereas the BLIJ_2090 gene-disrupted mutant did not. In vivo, administration of B. infantis and Gal-β1,4-Rha alleviated C. difficile infection-related weight loss in mice. We have successfully screened Gal-β1,4-Rha as a next-generation prebiotic candidate that specifically promotes the growth of beneficial bacteria without promoting the growth of prominent bacteria and pathogens.
Predictive modeling to create a proactive approach to patient blood management in the oncology population.
Authors: Sandra Rivas, Hecca Cox, Benjamin Mescher, Colleen Villamin, Tonita Bates, Fernando Martinez, Mayrin Correa Medina, Kimberly Klein
Journal: Journal of Clinical Oncology (2021)

332 Background: Patient safety concerns that arose during COVID-19, related to blood shortages at a large oncological transfusion center, foregrounded the need for predictive modeling tools to optimize blood product inventory control. A maximum surgical blood ordering schedule (MSBOS), is a tool used to assist clinicians in predicting intraoperative blood usage based on retrospective historical data within an institution. Although MSBOS proves to be valuable, it is rudimentary in nature. Not only is data collection cumbersome but the data generated may not reflect current surgical practices and inter-patient variability may skew procedural averages. Predictive blood modeling is contingent generation of a digital health dashboard (DHB). DHB are electronically embedded in the electronic health record (EHR) to collect perioperative data. Coupling the generated informatics (patient demographics, diagnosis, laboratory results, procedural type, medications/supplements, surgeon) with machine learning allows for creation of patient-centered predictive blood modeling algorithms and better inventory control. Methods: To characterize blood use across various procedures at our institution, we engaged information technology specialists to create a Web Intelligence report by integrating data from both an EHR and a lab information system (LIS) into a single repository. Information obtained illuminated a master procedure list, blood product usage patterns, and characterized patient demographics during January - March, 2020. Data is continuously extracted to create a perpetually updated MSBOS while secondarily functioning to cultivate data for future predictive machine learning algorithms. Results: Data analysis demonstrated 5598 procedures were performed during the first quarter of 2020. Procedures not transfused with packed red blood cells (pRBCs) totaled to 4,156 and 1,442 had a greater than or equal to 10% probability of requiring pRBCs. Our current practices reflected our overall crossmatch to transfusion ratio ( C:T) was 5.4 to 1. Concerted collaboration, resulting in preparation of pre-surgical blood product orders according laboratory generated MSBOS schedule could decrease the C:T to 1.7 to 1. Additionally, high intraprocedural pRBCs variability was identified in current procedural subtypes. Conclusions: Traditionally generated MSBOS are functionally limited and may not be reflective of current surgical practices. Additionally, inter-patient variability may distort some procedural type guidance. Creating an integrated data report, eliminates some of the inherent limitations of traditional MSBOS. Moving forward, the cultivated data if coupled with machine learning has the potential to create transferable proprietary algorithms that proactively predict individual patient transfusion needs.
Rotational thromboelastometry (rotem) profiling of covid-19 patients
Authors: N. Sabljic, M. Mitrovic, Z. Cvetkovic, N. Pantic, Z. Bukumiric, M. Virijevic, I. Milosevic, Z. Pravdic, N. Suvajdzic-Vukovic, J. Fareed, D. Antic
Journal: HemaSphere (2021)

Background: Thrombosis is frequently diagnosed in patients with Coronavirus disease (COVID - 19), despite the use of a standard-dose thromboprophylaxis in all hospitalized. Since conventional coagulation tests (CCTs) reflect only limited parts of the coagulation system and are insufficient to assess hypercoagulability, rotational thromboelastometry (ROTEM) could be more effective in identifying hypercoagulable pattern and patient in high-risk of thrombosis. Aims: 1. To analyze ROTEM parameters across the entire clinical COVID-19 pneumonia spectrum, from moderate to critical. 2. To determine the incidence of hypercoagulable ROTEM patterns and improve risk stratification. Methods: We evaluated coagulation abnormalities via CCTs and ROTEM in a group of 94 patients with confirmed SARS-CoV-2 infection and different severity of pneumonia (34 moderate, 25 severe, 35 critical). Shorter than normal clotting time (CT) and higher than normal maximum clot firmness (MCF) in both extrinsic pathway (EXTEM) and fibrinogen pathway (FIBTEM), as well as shorter than normal EXTEM clot formation time (CFT) and higher than normal α-angle were classified as markers of hypercoagulable state. Results: At least one hypercoagulable ROTEM parameter had 62 (66%) patients. Increment in the number of patients with ≥ 2 hypercoagulable parameters, higher EXTEM MCF (P = 0.0001), higher FIBTEM MCF (P = 0.0001) and decrement in maximum lysis (P = 0.002) were observedwith increment in disease severity (P = 0.0001). Significant positive correlations between interleukine - 6 (IL6) and CT EXTEM (P = 0.003), MCF EXTEM (P = 0.033), MCF FIBTEM (P = 0.01) as well as negative with ML EXTEM (P = 0.006) were seen. Contrary to hypercoagulable ROTEM pattern which was not predictive for death, hypocoagulability represented by prolonged EXTEM CT (P = 0.0001) and CFT (P = 0.0001), smaller α angle (P = 0.014) and a prolonged FIBTEM CT (P = .0001) was a predictor. Summary/Conclusion: Our findings confirmed that a hypercoagulable ROTEM pattern characterized by clot formation acceleration, high clot strength, and reduced fibrinolysis was more frequent in advanced disease groups and patients with high IL6. These results support the need for different thromboprophylaxis approaches for different severity groups.
Remote monitoring of vital and activity parameters in chronic transfusion dependent patients - A case-crossover pilot using wearable biosensors
Authors: R. Tonino, M. Tweardy, S. Wegerich, J. J. Zwaginga, M. Schipperus
Journal: HemaSphere (2021)

Background: Optimising red cell transfusion requires an understanding of both the risks and the benefits. Adverse events of red cell transfusions, like transfusion reactions and iron overload are reasons for considering a restrictive transfusion strategy. However, there are no completed trials in the outpatient setting for chronic transfusion-dependent patients, and little data in general about the value of outpatient transfusions. With no objective parameters to measure the benefits of red cell transfusions, a restrictive transfusion strategy may not be optimal for patients who require RBCT on a regular basis. Transfusions are ordered primarily based on haemoglobin concentrations and a subjective interpretation of symptoms of anaemia. Endpoints that may be more clinically relevant include quality of life measurements, vital signs, functional activity and cognition. To date, there has been little systematic assessment of tools that assess these measures and no published trials that have examined the impact of transfusions on functional outcomes in transfusion-dependent patients. Aims: The aim of this study is to understand how wearable devices and web-based testing can be used to measure physiological changes and functional activity in a cohort of transfusion-dependent patients. Methods: We monitored 5 patients who chronically receive transfusions during one transfusion cycle with the VitalPatch. and Withings Steel HR. Patients completed CANTAB cognitive tasks, QUALMS and PROMIS quality of life questionnaires through web-based testing. Outcomes were first the quality and usability of data. Second, we leveraged mixed models to evaluate transfusion-induced changes in 1) heart rate, 2) activity, 3) sustained attention, and 4) patient-reported quality of life. Results: Captured data was 97,8% high quality and usable for the VitalPatch;98,9% for the Withings Steel HR. The sent out web-based CANTAB tasks and questionnaires were all completed on the appointed days. Heart rate and sustained attention are significantly and reversibly affected by RBC transfusions, corrected for predefined confounders (Fig. 1): Mean daytime heart rate was 76.5±2.8 bpm before and 72.3±2.8 after transfusion (P=0.002). Sustained attention (RVPA) increased from 8586±140 to 9141±183 after transfusion (P=0.004). Activity and quality of life measures did not yield transfusion-induced changes. The measured activity data may not be representative as the study was conducted during the COVID-19 induced lockdown.
Myocardial injury after gynecologic oncology surgery in septuagenarians and octogenarians: Is there a role for routine postoperative cardiac biomarker monitoring?
Authors: Tharani Anpalagan, Kathy Huang, Maura Marcucci, Sarah Mah, Millie Walker, Vanessa Carlson, Lua Ruhiyyih Eiriksson, Waldo Jimenez, Clare Reade, Julie My Van Nguyen
Journal: Journal of Clinical Oncology (2021)

220 Background: Accumulating evidence correlates myocardial injury after noncardiac surgery (MINS), even when asymptomatic, with increased cardiac and non-cardiac morbidity and mortality. There is no literature on MINS specific to Gynecologic Oncology. We sought to evaluate the incidence and risk factors of MINS in patients aged ≥70. Methods: Elective laparotomies between 01/2016-09/2020 for patients aged≥70 at a tertiary hospital in ON, Canada, were reviewed using prospectively-collected National Surgical Quality Improvement Program (NSQIP) data. MINS was defined as peak serum high-sensitivity troponin-T concentration ≥0.04ng/mL within 30 days postoperatively. Logistic regression analysis was performed. Results: In this cohort of 258 patients, of 242 (93.8%) who underwent postoperative troponin screening, 40 (16.5%) experienced MINS without exhibiting ischemic symptoms or ECG changes. The diagnosis of MINS led to a prescription or optimization of cardiovascular medications for 35 patients (87.5%). On univariate analysis, Revised Cardiac Risk Index (RCRI) of 3-5(p = 0.002), history of coronary artery disease (p = 0.003) or insulin-dependent diabetes (p = 0.006), preoperative use of antiplatelets (p = 0.009), beta-blockers (p = 0.02), ACE-inhibitors (ACEI) or angiotensin-receptor blockers (ARB)(p = 0.002) and frailty as defined by the NSQIP modified frailty index-5 (p = 0.02), were associated with greater risk of MINS. Factors reflecting surgical complexity including surgical complexity score, operative duration, blood loss and advanced oncologic stage were not predictive. Multivariable analysis using backward selection procedure identified elevated RCRI and preoperative ACE/ARB as significant risk factors (OR 5.93, 95% CI 1.52-24.31, p = 0.01 and OR 2.4, 95% CI 1.18-5.06, p = 0.02). Conclusions: One in 6 patients in our cohort experienced asymptomatic MINS irrespective of surgical complexity. Our analysis highlights a possible opportunity to optimize cardiac risk factors and to potentially improve perioperative patient safety by reducing morbidity. Routine preoperative cardiac risk-stratification and postoperative cardiac biomarkers monitoring should be considered in elderly patients with gynecologic malignancies.[Table: see text]