tbuckley/cabot-search huggingface dataset:
CONTINUUM: A single-arm pilot care transition intervention for hospitalized patients with advanced cancer.
Authors: Daniel E Lage, Alane Schmelkin, Julia Cohn, Laurie Miller, Caroline Kuhlman, Elizabeth A. Krueger, Kara Marie Olivier, Dana Haggett, Christine Ritchie, Joseph A. Greer, Areej El-Jawahri, Ryan David Nipp, Jennifer S. Temel
Journal: Journal of Clinical Oncology (2021)

33 Background: Patients with advanced cancer are frequently hospitalized and experience burdensome transitions of care after discharge. Interventions to address patients’ symptoms, support medication management, and ensure continuity of care after discharge are lacking. We sought to demonstrate the feasibility and acceptability of CONTINUUM (CONTINUity of care Under Management by video visits) for this population. Methods: We conducted a single-arm pilot trial (n = 50) of CONTINUUM at Massachusetts General Hospital (MGH). The intervention consisted of a video visit with an oncology nurse practitioner (NP) within 3 business days of hospital discharge to address symptoms, medication management, hospitalization-related issues, and care coordination. Prior to discharge, we enrolled English-speaking adults with advanced breast, gastrointestinal, genitourinary, or thoracic cancers experiencing an unplanned hospitalization who were receiving ongoing oncology care at MGH and being discharged home without hospice services. We defined the intervention as feasible if ≥70% of approached and eligible patients enrolled and if ≥70% of enrolled patients completed the intervention within 3 business days of discharge. At 2 weeks after discharge, patients rated the ease of use of the video technology and stated whether they would recommend the intervention. NPs completed post-intervention surveys to assess fidelity to the intervention protocol. Results: From 01/07/21 to 05/28/21, we enrolled 50 patients (75% of patients approached). Of the enrolled patients (median age = 65 years; 62% and 22% had advanced gastrointestinal or thoracic cancers, respectively), 78% of enrolled patients received the intervention within 3 business days of discharge. Patient rating of the ease of use of video technology was a mean of 7.6 out of 10, with 72% stating they “agreed” or “strongly agreed” that they would recommend the intervention. NP post-intervention surveys revealed that visits primarily focused on symptom management (56%), followed by addressing post-hospital care issues (21%). Of the 30 patients with 30-day follow-up, 43% were readmitted within 30 days of discharge, and 17% died within 30 days of discharge. Conclusions: We found that CONTINUUM, which consists of an NP-delivered video visit soon after hospital discharge addressing patients’ symptoms, medications, and care coordination, represents a feasible and acceptable approach to provide post-discharge care for hospitalized patients with advanced cancer. Future studies will test the efficacy of the intervention for reducing hospital readmissions. Clinical trial information: NCT04640714.
Expanding control of the tumor cell cycle with a CDK2/4/6 inhibitor
Authors: Kevin Freeman-Cook, Robert L. Hoffman, Nichol Miller, Jonathan Almaden, John Chionis, Qin Zhang, Koleen Eisele, Chaoting Liu, Cathy Zhang, Nanni Huser, Lisa Nguyen, Cinthia Costa-Jones, Sherry Niessen, Jordan Carelli, John Lapek, Scott L. Weinrich, Ping Wei, Elizabeth McMillan, Elizabeth Wilson, Tim S. Wang, Michele McTigue, Rose Ann Ferre, You-Ai He, Sacha Ninkovic, Douglas Behenna, Khanh T. Tran, Scott Sutton, Asako Nagata, Martha A. Ornelas, Susan E. Kephart, Luke R. Zehnder, Brion Murray, Meirong Xu, James E. Solowiej, Ravi Visswanathan, Britton Boras, David Looper, Nathan Lee, Jadwiga R. Bienkowska, Zhou Zhu, Zhengyan Kan, Ying Ding, Xinmeng Jasmine Mu, Cecilia Oderup, Shahram Salek-Ardakani, Michael A. White, Todd VanArsdale, Stephen G. Dann
Journal: Cancer Cell (2021)
Comparison of viability and hematologic recovery after allogeneic transplantations with fresh or frozen in 5% dimethylsulphoxide (dmso) hematopoietic stem cells (hsc)
Authors: I. Tonev, M. Mincheff
Journal: HemaSphere (2021)

Background: In allogeneic transplantation the usual approach is to synchronize the conditioning of the patient with stem cell harvesting in order to infuse fresh cell products. The EBMT COVID-19 guidelines recommend cryopreservation of the graft to be considered if there is a concern that the donor is at risk of infection after the patient's conditioning is initiated. Aims: We analyzed if cell viability or hematological recovery is affected in case stem cells are previously frozen. Methods: Results from two groups of patients, each comprising of 16 males and 8 females, were analyzed. HSC from the first group were non-programmed frozen and stored at -80oC in a cryoprotective solution with a final 5% DMSO, 3.6% hydroxyethyl amylopectin (HES, Mw 450 000 Da) and 3% human serum albumin (HSA) concentrations. Platelets and plasma were removed from stem cell harvest prior to the addition of the cryoprotectant. The HSCs from the second group were transplanted without freezing. Fresh cell viability or viability after thawing (trypan blue exclusion test) and hematological recovery (neutrophils and platelets) of patients receiving cryopreserved cells or fresh cells were analyzed. Results: The average viability was 98,67 % (SD ±1,633) for fresh HSCs and 91,63% (SD ±8,021) for cryopreserved cells. The average time for hematological recovery for the neutrophils, was 17,96(SD ±4,601) for fresh cells and 16,46 (SD ± 4,530) for frozen cells. The average time for hematological recovery for the platelets, was 15,25 (SD ± 4,590) for fresh cells and 16,26 (SD ± 6,032) for frozen cells. There was no statistically significant difference between the two groups for hematological recovery. Summary/Conclusion: Use of fresh HSCs is the first choice for allogeneic stem cell transplantation. In cases of pandemics, such as the Covid-19 one, use of cells harvested and frozen prior to initiation of the condioning regimen is preferred. Cryopreservation of HSCs with a cryoprotective solution with low (5%) DMSO concentration and extracellular agents (hydroxyethyl amylopectin and HSA) is safe and well tolerated and gives excellent post thaw viability and post-transplant hematological recovery results.
It is time for consensus on ‘consensus statements’
Authors: Paul Blazey, Kay M Crossley, Clare L Ardern, Marienke van Middelkoop, Alex Scott, Karim M Khan
Journal: British Journal of Sports Medicine (2021)

The International Olympic Committee has published 27 ‘consensus statements’ since 2004.1 Many of them are heavily downloaded and highly cited. Several have influenced health policy and societal behaviour. Some consensus statements are so well-known they go by just one name in context: ‘Berlin’ means concussion, ‘Doha’ is synonymous with groin pain, and ‘Bern’ evokes return to play guidelines.

Despite their eminence, even the most respected consensus statements have limitations: relevant stakeholders are absent from the consensus process; authors inadequately report the method of evidence synthesis; consensus group members may be ‘coerced’ to agree; and the reports often fail to capture the rich discussion that occurs during a panel meeting.

We critically examine methods that underpin sport and exercise medicine consensus statements. Specifically, we: (1) question whether consensus statements deserve their prestige; (2) highlight bias in the current methods of developing consensus and (3) propose future steps to improve the quality of consensus statements by using reporting guidelines.

Expert opinion sits at the base of the evidence pyramid but when those experts gather, and take recent systematic reviews into account, their output—consensus statements—are given great weight. Consensus statements are some of the most downloaded and cited publications. …
Abstract 15582: Global, but Not Cardiac Specific, Knockout of ROMK Potassium Channels Worsens Cardiac Ischemia Reperfusion Injury
Authors: Kyriakos Papanicolaou, Deepthi Ashok, Ting Liu, Tyler Bauer, Zhen Li, Eduardo Da Costa, Charles Crepy, Sara Nathan, David J Lefer, Elizabeth Murphy, Nazareno Paolocci, D Brian Foster, Brian O’Rourke
Journal: Circulation (2019)

The renal-outer-medullary-potassium (ROMK) channel, mutated in heritable Bartter’s syndrome, regulates ion exchange in the nephron but its extra-renal functions remain poorly understood. ROMK is al...
Collateral effects of deletion of nlpD on rpoS and rpoS-dependent genes
Authors: Manami Tsunoi, Sunao Iyoda, Tadayuki Iwase
Journal: Journal of Clinical Investigation (2021)

A seminal article, titled "Active bacterial modification of the host environment through RNA polymerase II inhibition," was published in the JCI in February 2021 (1).The article depicts a novel bacterial phenomenon mediated by the NlpD protein, which was demonstrated using an nlpD deletion mutant, a recombinant NlpD protein (rNlpD), and an nlpD deletion mutant complemented with the nlpD-rpoS operon.The idea in this article is impressive and has a potential impact on bacteriology, especially for studies on NlpD.However, since nlpD is complicated, as marginally referred to in Supplemental Figure 5 in the article by Ambite et al., we here include detailed information about nlpD.nlpD is positioned upstream of rpoS; rpoS encodes the RNA polymerase sigma factor σ 38 (RpoS) that regulates many genes, as shown in a recent study that identified differential expression of 1044 genes between the wild-type and rpoS mutant (2).Importantly, nlpD includes rpoS promoters, including the P2 promoter, which is critical for rpoS expression (2-4).The nlpD deletion mutant lacks the rpoS promoter, resulting in no expression of both rpoS and nlpD.Whether the phenotypes observed in the nlpD deletion mutant depend on the NlpD functions should be confirmed using nlpD and not the nlpD-rpoS operon, and we have reviewed the article by Ambite et al. with this view in mind.An nlpD SNP observed in SN25 was mapped to the critical rpoS promoter P2 "TATAAT" (5).SN25 showed low or no expression of RpoS (Supplemental Figure 5B in the article by Ambite et al.), appearing to be a mutant with substantial RpoS deficiency.No nlpD deletion mutant complemented solely with nlpD was tested; however, the mutant complemented with the nlpD-rpoS operon that expressed RpoS in addition to NlpD was studied.Furthermore, since no experiment using rNlpD SNP to confirm the phenotypes of SN25 was performed, whether these phenotypes depend on a loss of function of NlpD remains to be determined.These approaches raise the possibility that the phenotypes of SN25 observed can be attributed to the effects of rpoS/rpoS-dependent genes.We believe that this information will be useful for future studies on hostmicrobe interactions, especially those focusing on nlpD.
Single-cell RNA sequencing profiling of mouse endothelial cells in response to pulmonary arterial hypertension
Authors: Julie Rodor, Shiau Haln Chen, Jessica P Scanlon, João P Monteiro, Axelle Caudrillier, Sweta Sweta, Katherine Ross Stewart, Alena Shmakova, Ross Dobie, Beth E P Henderson, Kevin Stewart, Patrick W F Hadoke, Mark Southwood, Stephen D Moore, Paul D Upton, Nick W Morrell, Ziwen Li, Stephen Y Chan, Adam Handen, Robert Lafyatis, Laura P M H de Rooij, Neil C Henderson, Peter Carmeliet, Ana Mishel Spiroski, Mairi Brittan, Andrew H Baker
Journal: Cardiovascular Research (2021)

Endothelial cell (EC) dysfunction drives the initiation and pathogenesis of pulmonary arterial hypertension (PAH). We aimed to characterize EC dynamics in PAH at single-cell resolution.We carried out single-cell RNA sequencing (scRNA-seq) of lung ECs isolated from an EC lineage-tracing mouse model in Control and SU5416/hypoxia-induced PAH conditions. EC populations corresponding to distinct lung vessel types, including two discrete capillary populations, were identified in both Control and PAH mice. Differential gene expression analysis revealed global PAH-induced EC changes that were confirmed by bulk RNA-seq. This included upregulation of the major histocompatibility complex class II pathway, supporting a role for ECs in the inflammatory response in PAH. We also identified a PAH response specific to the second capillary EC population including upregulation of genes involved in cell death, cell motility, and angiogenesis. Interestingly, four genes with genetic variants associated with PAH were dysregulated in mouse ECs in PAH. To compare relevance across PAH models and species, we performed a detailed analysis of EC heterogeneity and response to PAH in rats and humans through whole-lung PAH scRNA-seq datasets, revealing that 51% of up-regulated mouse genes were also up-regulated in rat or human PAH. We identified promising new candidates to target endothelial dysfunction including CD74, the knockdown of which regulates EC proliferation and barrier integrity in vitro. Finally, with an in silico cell ordering approach, we identified zonation-dependent changes across the arteriovenous axis in mouse PAH and showed upregulation of the Serine/threonine-protein kinase Sgk1 at the junction between the macro- and microvasculature.This study uncovers PAH-induced EC transcriptomic changes at a high resolution, revealing novel targets for potential therapeutic candidate development.
Anthelmintics nitazoxanide protects against experimental hyperlipidemia and hepatic steatosis in hamsters and mice
Authors: Fengfeng Li, Man Jiang, Minghui Ma, Xuyang Chen, Yidan Zhang, Yixin Zhang, Yuanyuan Yu, Yunfeng Cui, Jiahui Chen, Hui Zhao, Zhijie Sun, Deli Dong
Journal: Acta Pharmaceutica Sinica B (2021)

Lipid metabolism disorders contribute to hyperlipidemia and hepatic steatosis. It is ideal to develop drugs simultaneous improving both hyperlipidemia and hepatic steatosis. Nitazoxanide is an FDA-approved oral antiprotozoal drug with excellent pharmacokinetic and safety profile. We found that nitazoxanide and its metabolite tizoxanide induced mild mitochondrial uncoupling and subsequently activated AMPK in HepG2 cells. Gavage administration of nitazoxanide inhibited high-fat diet (HFD)-induced increases of liver weight, blood and liver lipids, and ameliorated HFD-induced renal lipid accumulation in hamsters. Nitazoxanide significantly improved HFD-induced histopathologic changes of hamster livers. In the hamsters with pre-existing hyperlipidemia and hepatic steatosis, nitazoxanide also showed therapeutic effect. Gavage administration of nitazoxanide improved HFD-induced hepatic steatosis in C57BL/6J mice and western diet (WD)-induced hepatic steatosis in
Machine learning-based approach to the risk assessment of potentially preventable outpatient cancer treatment-related emergency care and hospitalizations.
Authors: Kevin Miao, Justice Dahle, Sasha Yousefi, Bilwa Buchake, Parambir Kaur, Anobel Y. Odisho, Pelin Cinar, Julian C. Hong
Journal: Journal of Clinical Oncology (2021)

333 Background: Patients undergoing outpatient infusion chemotherapy for cancer are at risk for potentially preventable, unplanned acute care in the form of emergency department (ED) visits and hospital admissions. This can impact outcomes, patient decisions, and costs to the patient and healthcare system. To address this need, the Centers for Medicare &amp; Medicaid Services developed the Chemotherapy Measure (OP-35). Recent randomized controlled data indicate that electronic health record (EHR)-based machine learning (ML) approaches accurately direct supportive care to reduce acute care during radiotherapy. As this may extend to systemic therapy, this study aims to develop and evaluate ML approaches to predict the risk of OP-35 qualifying, potentially preventable acute care within 30 days of infusional systemic therapy. Methods: This study included data from UCSF cancer patients receiving infusional chemotherapy from July 1, 2017, to February 11, 2021, (total 7,068 patients over 84,174 treatments). The data incorporated into the ML included 430 EHR-derived variables, including cancer diagnosis, therapeutic agents, laboratory values, vital signs, medications, and encounter history. Three ML approaches were trained to predict an OP-35 acute care risk following a systemic therapy infusion with least absolute shrinkage selection operator (LASSO), random forest, and gradient boosted trees (GBT; XGBoost) approaches. The models were trained on a subset (75% of patients; before October 12, 2019) of the dataset and validated on a mutually exclusive subset (25% patients; after October 12, 2019) based on the receiver operating characteristic (ROC) curves and calibration plots. Results: There were 1,651 total acute care visits (244 ED visits and 1,407 ED visits converted into hospitalization); 1,310 infusions included a qualifying acute care visit (200 with ED visits only, 0 direct hospital admissions, and 1,110 with both ED visit and hospitalization). Each ML approach demonstrated good performance in the internal validation cohort, with GBT (AUC 0.805) outpacing the random forest (0.750) and LASSO logistic regression (0.755) approaches. Visualization of calibration plots verified concordance between predicted and observed rates of acute care. All three models shared patient age and days elapsed since last treatment as important contributors. Conclusions: EHR-based ML approaches demonstrate high predictive ability for OP-35 qualifying acute care rates on a per-infusion basis, identifying 30-day potentially preventable acute care risk for patients undergoing chemotherapy. Prospective validation of these models is ongoing. Early prediction can facilitate interventional strategies which may reduce acute care, improve health outcomes, and reduce costs.
Abstract 12450: Long-Term Efficacy and Safety of Lomitapide for the Treatment of Homozygous Familial Hypercholesterolemia: Results of the Phase 3 Extension Trial
Authors: Dirk Blom, Maurizio Averna, Emma Meagher, Hendrik du Toit Theron, Cesare Sirtori, Robert Hegele, Prediman Shah, Daniel Gaudet, Claudia Stefanutti, Giovanni Vigna, Pam Foulds, LeAnne Bloedon, Daniel Rader, Marina Cuchel
Journal: Circulation (2015)

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic condition characterized by highly elevated low-density lipoprotein cholesterol (LDL-C) levels and high cardiovascular disease risk. Lomitapide, an oral microsomal triglyceride transfer protein inhibitor, was approved for the treatment of adult HoFH based on a small phase 3 study. We report efficacy and safety results from the phase 3 long-term extension study. Methods: Eligible HoFH patients completing the 78-wk phase 3 pivotal trial were enrolled into a single-arm extension study where lomitapide was administered daily at the maximum tolerated dose (5-60mg/d) until lomitapide was commercially available in the patient’s country. Concurrent lipid-lowering therapies, including apheresis, were permitted. Results: Nineteen of 23 patients who completed the pivotal study entered the extension trial (9/19 apheresis) with 16 patients completing all end of study assessments. Mean treatment duration was 4.8 yrs (range 2.1-5.7 yrs, median 5.1 yrs). Lomitapide efficacy was maintained throughout the study (Table). Reported adverse events were similar to those in the pivotal phase 3 study (chiefly gastrointestinal). Five patients (26%) experienced transient alanine aminotransferase (ALT) elevations ≥5x upper limit of normal (ULN) that were successfully managed by dose adjustment in all but one patient who was discontinued due to persistent excessive alcohol use. One 58 year-old patient with known CAD had sudden cardiac death. Median hepatic fat increased by 10% above baseline after 3 yrs and stabilized through the treatment period (Table). No other clinically relevant findings were identified to date. Conclusions: The long-term efficacy of lomitapide was maintained up to 5.7 yrs in patients completing the phase 3 trial with no new safety signals observed. The clinical significance of the increase in hepatic fat remains unknown.
Risk factors for COVID-19 mortality in hospitalised children and adolescents in Brazil
Authors: Siyu Chen, Yong Shao
Journal: The Lancet Child & Adolescent Health (2021)

Surveillance Information System (SIVEP-GRIPE) dataset.Second, the authors should have men tioned that the risk factors included in SIVEP-GRIPE were selfreported (provided by the patients them selves or their families).Therefore, the analysis could be biased by the patients' knowledge regarding their medical condition.Additionally, some variables could be incorrectly coded in the electronic records; for instance, we identified in the current SIVEP-GRIPE platform at least 14 puerperal individuals younger than 10 years, which was probably a data entry error (leading to outliers).Finally, the author did not mention any effort to test the regression model assumptions (eg, non-linearity relationship and residual analysis).The inclusion of the variables in the final multivariate model was based on a univariate parameter, which could have suppressed other important variables that should be included in the model.There was also no internal validation or crossvalidation.Therefore, we believe that our concerns should affect how the data presented by Oliveira and colleagues 1 should be interpreted.
Comparative Effectiveness of Moderna, Pfizer-BioNTech, and Janssen (Johnson &amp; Johnson) Vaccines in Preventing COVID-19 Hospitalizations Among Adults Without Immunocompromising Conditions — United States, March–August 2021
Authors: Wesley H. Self, Mark W. Tenforde, Jillian P. Rhoads, Manjusha Gaglani, Adit A. Ginde, David J. Douin, Samantha M. Olson, H. Keipp Talbot, Jonathan D. Casey, Nicholas M. Mohr, Anne Zepeski, Tresa McNeal, Shekhar Ghamande, Kevin W. Gibbs, D. Clark Files, David N. Hager, Arber Shehu, Matthew E. Prekker, Heidi L. Erickson, Michelle N. Gong, Amira Mohamed, Daniel J. Henning, Jay S. Steingrub, Ithan D. Peltan, Samuel M. Brown, Emily T. Martin, Arnold S. Monto, Akram Khan, Catherine L. Hough, Laurence W. Busse, Caitlin C. ten Lohuis, Abhijit Duggal, Jennifer G. Wilson, Alexandra June Gordon, Nida Qadir, Steven Y. Chang, Christopher Mallow, Carolina Rivas, Hilary M. Babcock, Jennie H. Kwon, Matthew C. Exline, Natasha Halasa, James D. Chappell, Adam S. Lauring, Carlos G. Grijalva, Todd W. Rice, Ian D. Jones, William B. Stubblefield, Adrienne Baughman, Kelsey N. Womack, Christopher J. Lindsell, Kimberly W. Hart, Yuwei Zhu, Lisa Mills, Sandra N. Lester, Megan M. Stumpf, Eric A. Naioti, Miwako Kobayashi, Jennifer R. Verani, Natalie J. Thornburg, Manish M. Patel, Nicole Calhoun, Kempapura Murthy, Judy Herrick, Amanda McKillop, Eric Hoffman, Martha Zayed, Michael Smith, Natalie Seattle, Jason Ettlinger, Elisa Priest, Jennifer Thomas, Alejandro Arroliga, Madhava Beeram, Ryan Kindle, Lori-Ann Kozikowski, Lesley De Souza, Scott Ouellette, Sherell Thornton-Thompson, Omar Mehkri, Kiran Ashok, Susan Gole, Alexander King, Bryan Poynter, Nicholas Stanley, Audrey Hendrickson, Ellen Maruggi, Tyler Scharber, Jeffrey Jorgensen, Robert Bowers, Jennifer King, Valerie Aston, Brent Armbruster, Richard E. Rothman, Rahul Nair, Jen-Ting Tina Chen, Sarah Karow, Emily Robart, Paulo Nunes Maldonado, Maryiam Khan, Preston So, Joe Levitt, Cynthia Perez, Anita Visweswaran, Jonasel Roque, Adreanne Rivera, Los Angeles, Trevor Frankel, Los Angeles, Jennifer Goff, David Huynh, Michelle Howell, Jennifer Friedel, Michael Tozier, Conner Driver, Michael Carricato, Alexandra Foster, Paul Nassar, Lori Stout, Zita Sibenaller, Alicia Walter, Jasmine Mares, Logan Olson, Bradley Clinansmith, Carolina Rivas, Hayley Gershengorn, EJ McSpadden, Rachel Truscon, Anne Kaniclides, Lara Thomas, Ramsay Bielak, Weronika Damek Valvano, Rebecca Fong, William J. Fitzsimmons, Christopher Blair, Andrew L. Valesano, Julie Gilbert, Christine D. Crider, Kyle A. Steinbock, Thomas C. Paulson, Layla A. Anderson, Christy Kampe, Jakea Johnson, Rendie McHenry, Marcia Blair, Douglas Conway, Mary LaRose, Leigha Landreth, Madeline Hicks, Lisa Parks, Jahnavi Bongu, David McDonald, Candice Cass, Sondra Seiler, David Park, Tiffany Hink, Meghan Wallace, Carey-Ann Burnham, Olivia G. Arter
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Data are not complete for all characteristics in the table; denominators