tbuckley/cabot-search huggingface dataset:
Improving Suicide Prevention Through Evidence-Based Strategies: A Systematic Review
Authors: J. John Mann, Christina A. Michel, Randy P. Auerbach
Journal: American Journal of Psychiatry (2021)

Objective: The authors sought to identify scalable evidence-based suicide prevention strategies. Methods: A search of PubMed and Google Scholar identified 20,234 articles published between September 2005 and December 2019, of which 97 were randomized controlled trials with suicidal behavior or ideation as primary outcomes or epidemiological studies of limiting access to lethal means, using educational approaches, and the impact of antidepressant treatment. Results: Training primary care physicians in depression recognition and treatment prevents suicide. Educating youths on depression and suicidal behavior, as well as active outreach to psychiatric patients after discharge or a suicidal crisis, prevents suicidal behavior. Meta-analyses find that antidepressants prevent suicide attempts, but individual randomized controlled trials appear to be underpowered. Ketamine reduces suicidal ideation in hours but is untested for suicidal behavior prevention. Cognitive-behavioral therapy and dialectical behavior therapy prevent suicidal behavior. Active screening for suicidal ideation or behavior is not proven to be better than just screening for depression. Education of gatekeepers about youth suicidal behavior lacks effectiveness. No randomized trials have been reported for gatekeeper training for prevention of adult suicidal behavior. Algorithm-driven electronic health record screening, Internet-based screening, and smartphone passive monitoring to identify high-risk patients are understudied. Means restriction, including of firearms, prevents suicide but is sporadically employed in the United States, even though firearms are used in half of all U.S. suicides. Conclusions: Training general practitioners warrants wider implementation and testing in other nonpsychiatrist physician settings. Active follow-up of patients after discharge or a suicide-related crisis should be routine, and restricting firearm access by at-risk individuals warrants wider use. Combination approaches in health care systems show promise in reducing suicide in several countries, but evaluating the benefit attributable to each component is essential. Further suicide rate reduction requires evaluating newer approaches, such as electronic health record–derived algorithms, Internet-based screening methods, ketamine’s potential benefit for preventing attempts, and passive monitoring of acute suicide risk change.
Abstract PS16-22: Targeting resistance to current CDK4/6 therapies by RGT-419B, an inhibitor with optimized kinase activity spectrum
Authors: Zhi Xie, Jing Han, Zhilong Hu, Hu He, Xianqiang Sun, Fei Zhang, Jing Lin, Lili Yao, Xinjuan Wang, Liufeng Mei, Yangyang Liu, Guoyun Zhu, Xi Chen, Xiaotian Zhu, Wenge Zhong
Journal: Cancer Research (2021)

Abstract Cyclin-dependent kinases (CDKs) 4/6 inhibitors are a powerful class of therapeutic drugs for the treatment of advanced metastatic breast cancer. However, the currently approved CDK4/6 inhibitors palbociclib, ribociclib and abemaciclib have dose-limiting toxicities that require treatment holidays or reductions to sub-optimal doses, thus limiting full target inhibition. The residual CDK4/6 activity, together with persistent signaling through CDK2/cyclin E are among key resistant mechanisms that can compromise full clinical benefit. RGT-419B is a 3rd generation CDK inhibitor with an optimized kinase activity spectrum that has been discovered employing a Computer Accelerated Rational Design technology platform. RGT-419B has potent sub-nM CDK4 activity with desired degrees of selectivity against kinases such as CDK6, CDK9 and GSK3β to enable full target engagement with an improved safety profile. Furthermore, single digit nM CDK2 kinase activity has been incorporated into the design of RGT-419B to combat Cyclin E/CDK2-driven resistance. In vitro, RGT-419B showed more robust activity against palbociclib-resistant ER+ breast cancer cells than abemaciclib. In ER+ T47D breast cancer cells with overexpression of Cyclin E1, RGT-419B exhibited better antiproliferation activity than either abemaciclib or palbociclib. RGT-419B also demonstrated more durable in vivo tumor growth inhibition when compared with abemaciclib in an ER+ breast cancer xenograft model. The optimized kinase activity spectrum of RGT-419B provides an opportunity to treat ER+ breast cancer patients refractory to the existing CDK4/6 inhibitors, as either a single agent or in combination with other therapies. Citation Format: Zhi Xie, Jing Han, Zhilong Hu, Hu He, Xianqiang Sun, Fei Zhang, Jing Lin, Lili Yao, Xinjuan Wang, Liufeng Mei, Yangyang Liu, Guoyun Zhu, Xi Chen, Xiaotian Zhu, Wenge Zhong. Targeting resistance to current CDK4/6 therapies by RGT-419B, an inhibitor with optimized kinase activity spectrum [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS16-22.
Screening for Candida auris in patients admitted to eight intensive care units in England, 2017 to 2018
Authors: Ashley Sharp, Berit Muller-Pebody, Andre Charlett, Bharat Patel, Rebecca Gorton, Jonathan Lambourne, Martina Cummins, Adela Alcolea-Medina, Mark Wilks, Robin Smith, Damien Mack, Susan Hopkins, Andrew Dodgson, Phillipa Burns, Nelun Perera, Felicia Lim, Gopal Rao, Priya Khanna, Elizabeth Johnson, Andrew Borman, Silke Schelenz, Rebecca Guy, Joanna Conneely, Rohini J Manuel, Colin S Brown
Journal: Eurosurveillance (2021)

Background Candida auris is an emerging multidrug-resistant fungal pathogen associated with bloodstream, wound and other infections, especially in critically ill patients. C. auris carriage is persistent and is difficult to eradicate from the hospital environment. Aim We aimed to pilot admission screening for C. auris in intensive care units (ICUs) in England to estimate prevalence in the ICU population and to inform public health guidance. Methods Between May 2017 and April 2018, we screened admissions to eight adult ICUs in hospitals with no previous cases of C. auris, in three major cities. Swabs were taken from the nose, throat, axilla, groin, perineum, rectum and catheter urine, then cultured and identified using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS). Patient records were linked to routine ICU data to describe and compare the demographic and health indicators of the screened cohort with a national cohort of ICU patients admitted between 2016 and 2017. Results All C. auris screens for 921 adults from 998 admissions were negative. The upper confidence limit of the pooled prevalence across all sites was 0.4%. Comparison of the screened cohort with the national cohort showed it was broadly similar to the national cohort with respect to demographics and co-morbidities. Conclusion These findings imply that C. auris colonisation among patients admitted to ICUs in England is currently rare. We would not currently recommend widespread screening for C. auris in ICUs in England. Hospitals should continue to screen high-risk individuals based on local risk assessment.
Evaluating the safety of using G-CSF prophylaxis during concurrent chemotherapy and thoracic irradiation in patients with limited-stage small-cell lung cancer (LS-SCLC): evidence from a phase II trial
Authors: Rovel J. Colaco, Hamid Y. Sheikh, Linda Ashcroft, Fiona H. Blackhall, Paul C. Lorigan, Paul Taylor, Nicholas Thatcher, Corinne Faivre-Finn
Journal: Journal of Thoracic Oncology (2009)
Durvalumab for Stage III EGFR-Mutated NSCLC After Definitive Chemoradiotherapy
Authors: Jacqueline V. Aredo, Isa Mambetsariev, Jessica A. Hellyer, Arya Amini, Joel W. Neal, Sukhmani K. Padda, Caroline E. McCoach, Jonathan W. Riess, Elwyn C. Cabebe, Jarushka Naidoo, Tariq Abuali, Ravi Salgia, Billy W. Loo, Maximilian Diehn, Summer S. Han, Heather A. Wakelee
Journal: Journal of Thoracic Oncology (2021)
Grounded procedures of separation in clinical psychology: what's to be expected?
Authors: Anke Haberkamp, Thomas Schmidt
Journal: Behavioral and Brain Sciences (2021)

Abstract The hypothesis of grounded procedures of separation predicts accentuated effects in individuals with psychiatric disorders, for example, obsessive-compulsive disorders with washing compulsion. This could provide a vantage point for understanding cognitive processes related to specific disorders. However, fully exploring it requires updated experimental designs, including extensive control conditions, exclusion of alternative explanations, internal replications, and parametric variation to strengthen internal validity.
Does additional reconstruction of the anterolateral ligament during a primary anterior cruciate ligament reconstruction affect tibial rotational laxity? – A case series
Authors: R. Shah, R. Singh, C. Dugdale, G. Geutjens
Journal: International Journal of Surgery (2016)

Abstract   Background  The current evidence suggests that rotational stability in not restored in patients with anterior cruciate ligament (ACL) ruptures, despite reconstructive surgery. The graded pivot-shift is a useful clinical test to delineate extent of ligamentous laxity within the knee. Given its lateralised position, we hypothesized that reconstruction of the anterolateral ligament (ALL) would provide restraint to excessive internal rotation, restoring rotational stability.    Methods  10 patients with MRI confirmed diagnosis of an isolated ACL rupture were included. Patients assigned a grade-3 pivot-shift underwent dual-ligament reconstruction for the ACL and ALL (Group 2), whilst patients with an absent pivot-shift, grade-1 or grade-2 underwent single ligament reconstruction for just the ACL (Group 1). Total range of rotation (TRR) was measured using a 3D-kinematic system at 30°,60°and 90° of knee flexion. Data was collected on the pathology-free contralateral normal knee (CNK), ACL-deficient knee (ADK) and the ACL-reconstructed knee (ARK).    Results  A statistically significant pre-operative difference in TRR between the CNK and ADK was noted between Group 1 and 2 (4.04° vs. 1.53°; p  and  percentage reduction in TRR at 30° of knee flexion was significantly higher in Group-2 compared to Group-1 (−8.15° vs. −2.96°; p     Conclusion  Our findings are based primarily in anaesthetized patients, with kinematic values at time-zero postoperatively. Patients presenting with significant rotational instability following a primary ACL injury and assessed to have a grade-3 pivot-shift may benefit from dual-ligament reconstruction. Further research is required to assess long-term patient-centered clinical outcomes.
High Detection Rates of Pancreatic Cancer Across Stages by Plasma Assay of Novel Methylated DNA Markers and CA19-9
Authors: Shounak Majumder, William R. Taylor, Patrick H. Foote, Calise K. Berger, Chung Wah Wu, Douglas W. Mahoney, William R. Bamlet, Kelli N. Burger, Neil Postier, Jaime de la Fuente, Karen A. Doering, Graham P. Lidgard, Hatim T. Allawi, Gloria M. Petersen, Suresh T. Chari, David A. Ahlquist, John B. Kisiel
Journal: Clinical Cancer Research (2021)

Abstract Purpose: We have previously identified tissue methylated DNA markers (MDMs) associated with pancreatic ductal adenocarcinoma (PDAC). In this case–control study, we aimed to assess the diagnostic performance of plasma MDMs for PDAC. Experimental Design: Thirteen MDMs (GRIN2D, CD1D, ZNF781, FER1L4, RYR2, CLEC11A, AK055957, LRRC4, GH05J042948, HOXA1, PRKCB, SHISA9, and NTRK3) were identified on the basis of selection criteria applied to results of prior tissue experiments and assays were optimized in plasma. Next, 340 plasma samples (170 PDAC cases and 170 controls) were assayed using target enrichment long-probe quantitative amplified signal method. Initially, 120 advanced-stage PDAC cases and 120 healthy controls were used to train a prediction algorithm at 97.5% specificity using random forest modeling. Subsequently, the locked algorithm derived from the training set was applied to an independent blinded test set of 50 early-stage PDAC cases and 50 controls. Finally, data from all 340 patients were combined, and cross-validated. Results: The cross-validated area under the receiver operating characteristic curve (AUC) for the training set was 0.93 (0.89–0.96) for the MDM panel alone, 0.91 (95% confidence interval, 0.87–0.96) for carbohydrate antigen 19-9 (CA19-9) alone, and 0.99 (0.98–1) for the combined MDM-CA19-9 panel. In the test set of early-stage PDAC, the AUC for MDMs alone was 0.84 (0.76–0.92), CA19-9 alone was 0.87 (0.79–0.94), and combined MDM-CA19-9 panel was 0.90 (0.84–0.97) significantly better compared with either MDMs alone or CA19-9 alone (P = 0.0382 and 0.0490, respectively). At a preset specificity of 97.5%, the sensitivity for the combined panel in the test set was 80% (28%–99%) for stage I disease and 82% (68%–92%) for stage II disease. Using the combined datasets, the cross-validated AUC was 0.9 (0.86–0.94) for the MDM panel alone and 0.89 for CA19-9 alone (0.84–0.93) versus 0.97 (0.94–0.99) for the combined MDM-CA19-9 panel (P ≤ 0.0001). Overall, cross-validated sensitivity of MDM-CA19-9 panel was 92% (83%–98%), with an observed specificity of 92% at the preset specificity of 97.5%. Conclusions: Plasma MDMs in combination with CA19-9 detect PDAC with significantly higher accuracy compared with either biomarker individually.
Abstract 13980: Cardiac Magnetic Resonance Imaging Quantification of Myocardial Ischemia and Necrosis Using a Novel Risk Prediction Model Allows for Better Risk Stratification in Coronary Artery Disease
Authors: Dominik Buckert, Nils Dyckmanns, Volker Rasche, Wolfgang Rottbauer, Peter Bernhardt
Journal: Circulation (2015)

Background: Cardiac magnetic resonance imaging (CMR) provides information about inducible myocardial ischemia and necrosis in one single examination in coronary artery disease (CAD) patients. Both variables have been shown to correlate with prognosis. However, there is no consensus on how to assess and quantify these two variables. Hypothesis: Objective of the present prospective study in consecutive patients was to provide a simple algorithm for quantification of ischemia and necrosis and to test for risk stratification models. Methods: Patients with known or suspected CAD referred for adenosine-stress CMR were consecutively enrolled from 2003 to 2007. Examination was conducted on a 1.5-T whole-body scanner. Reversible ischemia was diagnosed by adenosine stress first pass perfusion imaging. Myocardial necrosis was assessed by late gadolinium enhancement (LGE). In a semiautomatic approach, extent of reversible ischemia and scar was quantified and reported as percentage of the left ventricle. Primary endpoint was defined as cardiac death, non-fatal myocardial infarction and stroke. Results: The study cohort consisted of 845 patients. Median age was 64 years, 271 patients were women. During a median follow-up period of 3.8 years 61 primary endpoints occurred. Statistical analysis yielded a ≥6% optimal threshold for reversible ischemia to predict a primary endpoint (univariate hazard ratio 4.91, p&lt;.0001). Similarly, thresholds for extent of myocardial necrosis were defined (LGE &gt;15% and ≤33%: univariate hazard ratio 2.75, p&lt;.0001; LGE &gt;33%: univariate hazard ratio 16.27, p&lt;.0001). The risk prediction model containing both, quantified ischemia and necrosis, proved to be superior in comparison to the dichotomous model (ischemia present: yes/no; necrosis present: yes/no) on multivariate testing (increase in χ 2 -values: 45.004 to 61.545; increase in integrated discrimination improvement: .02269 to .03187; net reclassification index for optimal model: .25593, p=.001). Conclusion: CMR cut-off values for quantification of myocardial ischemia (≥6%) and necrosis (&gt;15% and &gt;33%) have been found which allow for better risk stratification in CAD patients. The combination of both has been shown to yield the superior risk stratification model.
FLT3 inhibitor lestaurtinib plus chemotherapy for newly diagnosed KMT2A-rearranged infant acute lymphoblastic leukemia: Children’s Oncology Group trial AALL0631
Authors: Patrick A. Brown, John A. Kairalla, Joanne M. Hilden, ZoAnn E. Dreyer, Andrew J. Carroll, Nyla A. Heerema, Cindy Wang, Meenakshi Devidas, Lia Gore, Wanda L. Salzer, Naomi J. Winick, William L. Carroll, Elizabeth A. Raetz, Michael J. Borowitz, Donald Small, Mignon L. Loh, Stephen P. Hunger
Journal: Leukemia (2021)
Baseline Comorbidities and Cardiac Biomarkers are Associated With In-hospital Mortality of Covid-19 Patients
Authors: E. Koutroumpakis, T. Thannoun, J. Pang, R. Patel, C. Grable, S. Damaraju, S. B. Mawji, M. Folivi, S. Chauhan, M. Fatakdawala, C. Powell, M. A. Shabbir, E. Philbin, R. Lyubarova, N. L. Palaskas, A. Deswal, H. Taegtmeyer, E. Garcia-Sayan
Journal: Circulation (2020)
Gut mucosa alterations and loss of segmented filamentous bacteria in type 1 diabetes are associated with inflammation rather than hyperglycaemia
Authors: Matthieu Rouland, Lucie Beaudoin, Ophélie Rouxel, Léo Bertrand, Lucie Cagninacci, Azadeh Saffarian, Thierry Pedron, Dalale Gueddouri, Sandra Guilmeau, Anne-Françoise Burnol, Latif Rachdi, Asmaa Tazi, Juliette Mouriès, Maria Rescigno, Nathalie Vergnolle, Philippe Sansonetti, Ute Christine Rogner, Agnès Lehuen
Journal: Gut (2021)

Type 1 diabetes (T1D) is an autoimmune disease caused by the destruction of pancreatic β-cells producing insulin. Both T1D patients and animal models exhibit gut microbiota and mucosa alterations, although the exact cause for these remains poorly understood. We investigated the production of key cytokines controlling gut integrity, the abundance of segmented filamentous bacteria (SFB) involved in the production of these cytokines, and the respective role of autoimmune inflammation and hyperglycaemia.We used several mouse models of autoimmune T1D as well as mice rendered hyperglycaemic without inflammation to study gut mucosa and microbiota dysbiosis. We analysed cytokine expression in immune cells, epithelial cell function, SFB abundance and microbiota composition by 16S sequencing. We assessed the role of anti-tumour necrosis factor α on gut mucosa inflammation and T1D onset.We show in models of autoimmune T1D a conserved loss of interleukin (IL)-17A, IL-22 and IL-23A in gut mucosa. Intestinal epithelial cell function was altered and gut integrity was impaired. These defects were associated with dysbiosis including progressive loss of SFB. Transfer of diabetogenic T-cells recapitulated these gut alterations, whereas induction of hyperglycaemia with no inflammation failed to do so. Moreover, anti-inflammatory treatment restored gut mucosa and immune cell function and dampened diabetes incidence.Our results demonstrate that gut mucosa alterations and dysbiosis in T1D are primarily linked to inflammation rather than hyperglycaemia. Anti-inflammatory treatment preserves gut homeostasis and protective commensal flora reducing T1D incidence.
Association of Cryoprecipitate Use With Survival After Major Trauma in Children Receiving Massive Transfusion
Authors: Maria A. Tama, Melvin E. Stone, Stephen M. Blumberg, Srinivas H. Reddy, Edward E. Conway, James A. Meltzer
Journal: JAMA Surgery (2021)

Although most massive transfusion protocols incorporate cryoprecipitate in the treatment of hemorrhaging injured patients, minimal data exist on its use in children, and whether its addition improves their survival is unclear.To determine whether cryoprecipitate use for injured children who receive massive transfusion is associated with lower mortality.This retrospective cohort study included injured patients examined between January 1, 2014, and December 31, 2017, at one of multiple centers across the US and Canada participating in the Pediatric Trauma Quality Improvement Program. Patients were aged 18 years or younger and had received massive transfusion, which was defined as at least 40 mL/kg of total blood products in the first 4 hours after emergency department arrival. Exclusion criteria included hospital transfer, arrival without signs of life, time of death or hospital discharge not recorded, and isolated head injuries. To adjust for potential confounding, a propensity score for treatment was created and inverse probability weighting was applied. The propensity score accounted for age, sex, race/ethnicity, injury type, payment type, Glasgow Coma Scale score, hypoxia, hypotension, assisted respirations, chest tube status, Injury Severity Score, total volume of blood products received, hemorrhage control procedure, hospital size, academic status, and trauma center designation. Data were analyzed from December 11, 2019, to August 31, 2020.Cryoprecipitate use within the first 4 hours of emergency department arrival.In-hospital 24-hour and 7-day mortality.Of the 2387 injured patients who received massive transfusion, 1948 patients were eligible for analysis. The median age was 16 years (interquartile range, 9-17 years), 1382 patients (70.9%) were male, and 807 (41.4%) were White. A total of 541 patients (27.8%) received cryoprecipitate. After propensity score weighting, patients who received cryoprecipitate had a significantly lower 24-hour mortality when compared with those who did not (adjusted difference, -6.9%; 95% CI, -10.6% to -3.2%). Moreover, cryoprecipitate use was associated with a significantly lower 7-day mortality but only in children with penetrating trauma (adjusted difference, -9.2%; 95% CI, -15.4% to -3.0%) and those transfused at least 100 mL/kg of total blood products (adjusted difference, -7.7%; 95% CI, -15.0% to -0.5%).In this cohort study, early use of cryoprecipitate was associated with lower 24-hour mortality among injured children who required massive transfusion. The benefit of cryoprecipitate appeared to persist for 7 days only in those with penetrating trauma and in those who received extremely large-volume transfusion.
Expanding the Coverage of Metabolic Landscape in Cultivated Rice with Integrated Computational Approaches
Authors: Xuetong Li, Hongxia Zhou, Ning Xiao, Xueting Wu, Yuanhong Shan, Longxian Chen, Cuiting Wang, Zixuan Wang, Jirong Huang, Aihong Li, Xuan Li
Journal: Genomics Proteomics & Bioinformatics (2021)