tbuckley/cabot-search huggingface dataset:
Detection of ovarian cancer by elevated urinary levels of Bcl-2
Authors: Patricia A. Kruk, Yira Bermudez, Beatriz O. Saunders, George D. Wilbanks, Alan Cantor, Santo V. Nicosia
Journal: Cancer Research (2006)

2418  Ovarian cancer has the highest mortality among gynecological cancers. The lack of early symptoms and the absence of a reliable screening test to detect ovarian cancer result in over 70% of women being diagnosed after the disease has spread beyond the ovary so that the prognosis is poor (5-year survival is no better than 37%). Deregulation of apoptosis due to overexpression of anti-apoptotic proteins contributes to the malignant phenotype by supporting cancer cell growth and therapeutic resistance. To assess whether urinary levels of the anti-apoptotic protein, Bcl-2, could be used to detect ovarian cancer, urine was collected from normal healthy volunteers (N=18), patients with benign gynecologic disease (N=38) and patients with ovarian cancer (N=35) and measured for Bcl-2 by ELISA (mean ng/ml ± S.E.). The average amount of Bcl-2 in the urine of cancer patients was > 2 ng/ml and generally at least 10X greater than healthy controls or patients with benign disease (p   35 U/ml only identified 68% of ovarian cancer patients. Urinary levels of Bcl-2 decreased up to 100% in ovarian cancer patients following debulking surgery and remained low during chemotherapy, but increased significantly with recurrence of disease. Comparison of clinical parameters indicated that urinary levels of Bcl-2 correlated well with tumor stage and grade. However, urinary levels of Bcl-2 were not related to patient age or tumor size. Therefore, quantification of urinary Bcl-2 by ELISA-based assay appears to provide a safe, sensitive, specific and economical method to detect ovarian cancer, to monitor ovarian cancer throughout the course of disease and, possibly, to predict therapeutic and prognostic outcome. Clearly, the robust performance of urinary Bcl-2 as a marker of ovarian cancer warrants further investigation.
Association of Traumatic Injury With Adverse Pregnancy Outcomes in Taiwan, 2004 to 2014
Authors: Chih-Wei Pai, Bayu Satria Wiratama, Hsiao-Yu Lin, Ping-Ling Chen
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Literature has suggested that trauma among pregnant women is associated with an increased risk of adverse pregnancy outcomes. However, limited research has investigated the association of trauma with adverse pregnancy outcomes by using a national data set. <h3>Objective</h3> To investigate the association between traumatic injury and adverse pregnancy outcomes. <h3>Design, Setting, and Participants</h3> This population-based cohort study of pregnant women in Taiwan linked 3 data sets, the Taiwan Birth Registry, Household Registration Information, and National Health Insurance Research Database, from January 1, 2004, through December 31, 2014. Data, including the characteristics of pregnant women and infants, were extracted from the Taiwan Birth Registry data set; to obtain trauma data, this data set and the Household Registration Information data set were collectively linked to National Health Insurance Research Database data. The combined data set was analyzed from January to July 2019. Adverse pregnancy outcomes and premature delivery were defined using<i>International Classification of Diseases, Ninth Revision, Clinical Modification</i>codes. <h3>Exposures</h3> The primary exposures of this study were 2 clinical variables related to injury during pregnancy: medical treatment in the emergency department (yes or no) and hospitalization (yes or no). <h3>Main Outcomes and Measures</h3> The main outcome variable was adverse pregnancy outcomes, and the secondary outcome variable was premature delivery. Multivariate logistic regression models were used to investigate the association of injuries with adverse pregnancy outcomes after controlling for demographic characteristics and other pregnancy-related variables. <h3>Results</h3> A total of 2 973 831 pregnant women (2 475 805 [83.3%] aged 20-34 years) were enrolled between 2004 and 2014, of whom 59 681 (2.0%) sought medical treatments due to injuries. Results of multivariate logistic regression models showed that women receiving emergency treatments more than once were 1.08 times as likely (adjusted odds ratio, 1.08; 95% CI, 1.05-1.10) to have adverse pregnancy outcomes than women who received no emergency treatment. Women with injury-related hospitalization were 1.53 times more likely (adjusted odds ratio, 1.53; 95% CI, 1.41-1.65) to have adverse pregnancy outcomes than women who did not sustain injuries. Furthermore, recurrent injuries were associated with a 572% increase in odds of premature delivery (adjusted odds ratio, 6.72; 95% CI, 2.86-15.80). <h3>Conclusions and Relevance</h3> In this study, trauma among pregnant women was associated with an increased risk of adverse pregnancy outcomes, as were hospitalization and emergency department visits due to injury.
Treatment of myocardial infarction in the United States (1990 to 1993). Observations from the National Registry of Myocardial Infarction.
Authors: W JRogers, L JBowlby, N CChandra, W JFrench, J MGore, C TLambrew, R MRubison, A JTiefenbrunn, W DWeaver
Journal: Circulation (1994)

BACKGROUNDMultiple clinical trials have provided guidelines for the treatment of myocardial infarction, but there is little documentation as to how consistently their recommendations are being implemented in clinical practice.METHODS AND RESULTSDemographic, procedural, and outcome data from patients with acute myocardial infarction were collected at 1073 US hospitals collaborating in the National Registry of Myocardial Infarction during 1990 through 1993. Registry hospitals composed 14.4% of all US hospitals and were more likely to have a coronary care unit and invasive cardiac facilities than nonregistry US hospitals. Among 240,989 patients with myocardial infarction enrolled, 84,477 (35.1%) received thrombolytic therapy. Thrombolytic recipients were younger, more likely to be male, presented sooner after onset of symptoms, and were more likely to have localizing ECG changes. Among the 60,430 patients treated with recombinant tissue-type plasminogen activator (rTPA), 23.2% received it in the coronary car...
Evaluating the potential economic and health impact of rotavirus vaccination in 63 middle-income countries not eligible for Gavi funding: a modelling study
Authors: Frédéric Debellut, Andrew Clark, Clint Pecenka, Jacqueline Tate, Ranju Baral, Colin Sanderson, Umesh Parashar, Deborah Atherly
Journal: The Lancet Global Health (2021)

Middle-income countries (MICs) that are not eligible for funding from Gavi, the Vaccine Alliance, have been slow to adopt rotavirus vaccines. Few studies have evaluated the cost-effectiveness and benefit-risk of rotavirus vaccination in these settings. We aimed to assess the potential economic and health impact of rotavirus vaccination in 63 MICs not eligible for funding from Gavi. In this modelling study, we estimated the cost-effectiveness and benefit-risk of rotavirus vaccination in 63 MICs not eligible to Gavi funding. We used an Excel-based proportionate outcomes model with a finely disaggregated age structure to estimate the number of rotavirus gastroenteritis cases, clinic visits, hospitalisations, and deaths averted by vaccination in children younger than 5 years over a 10-year period. We calculated cost-effectiveness ratios (costs per disability-adjusted life-years averted compared with no vaccination) and benefit-risk ratios (number of hospitalisations due to rotavirus gastroenteritis averted per excess hospitalisations due to intussusception). We evaluated three alternative vaccines available globally (Rotarix, Rotavac, and Rotasiil) and used information from vaccine manufacturers regarding anticipated vaccine prices. We ran deterministic and probabilistic uncertainty analyses. Over the period 2020-29, rotavirus vaccines could avert 77 million (95% uncertainty interval [UI] 51-103) cases of rotavirus gastroenteritis and 21 million (12-36) clinic visits, 3 million (1·4-5·6) hospitalisations, and 37 900 (25 900-55 900) deaths due to rotavirus gastroenteritis in 63 MICs not eligible for Gavi support. From a government perspective, rotavirus vaccination would be cost-effective in 48 (77%) of 62 MICs considered. The benefit-risk ratio for hospitalisations prevented versus those potentially caused by vaccination exceeded 250:1 in all countries. In most MICs not eligible for Gavi funding, rotavirus vaccination has high probability to be cost-effective with a favourable benefit-risk profile. Policy makers should consider this new evidence when making or revisiting decisions on the use of rotavirus vaccines in their respective countries. Bill & Melinda Gates Foundation.
Abstract 15507: Effect of Intensive Blood Pressure Control on Residual Lifespan in the SPRINT Trial
Authors: Muthiah Vaduganathan, Brian Claggett, Stephen P Juraschek, Scott D Solomon
Journal: Circulation (2019)

Background: SPRINT (Systolic Blood Pressure Intervention Trial) showed that intensive blood pressure (BP) control (systolic BP target <120mmHg) was superior to standard BP control (<140mmHg), reduc...
Antidepressants: Evidence on safe discontinuation is lacking, concludes Cochrane review
Authors: Ingrid Torjesen
Journal: BMJ (2021)

Good quality evidence is urgently needed to inform doctors on how to discontinue antidepressants safely and effectively, a Cochrane review has highlighted.1

An international team of researchers assessed randomised controlled trials comparing approaches to discontinuation and continuation of antidepressants in patients who had used them for depression or anxiety for at least six months. But the team reached no firm conclusions about the effects and safety of the approaches reviewed because of the low certainty of evidence from the existing studies.

Ellen Van Leeuwen, lead author from the Clinical Pharmacology …
CD8+ T cells specific for an immunodominant SARS-CoV-2 nucleocapsid epitope display high naive precursor frequency and TCR promiscuity
Authors: Thi H.O. Nguyen, Louise C. Rowntree, Jan Petersen, Brendon Y. Chua, Luca Hensen, Lukasz Kedzierski, Carolien E. van de Sandt, Priyanka Chaurasia, Hyon-Xhi Tan, Jennifer R. Habel, Wuji Zhang, Lilith F. Allen, Linda Earnest, Kai Yan Mak, Jennifer A. Juno, Kathleen Wragg, Francesca L. Mordant, Fatima Amanat, Florian Krammer, Nicole A. Mifsud, Denise L. Doolan, Katie L. Flanagan, Sabrina Sonda, Jasveen Kaur, Linda M. Wakim, Glen P. Westall, Fiona James, Effie Mouhtouris, Claire L. Gordon, Natasha E. Holmes, Olivia C. Smibert, Jason A. Trubiano, Allen C. Cheng, Peter Harcourt, Patrick Clifton, Jeremy Chase Crawford, Paul G. Thomas, Adam K. Wheatley, Stephen J. Kent, Jamie Rossjohn, Joseph Torresi, Katherine Kedzierska
Journal: Immunity (2021)
Antiviral activity and safety of the hepatitis B core inhibitor ABI-H0731 administered with a nucleos(t)ide reverse transcriptase inhibitor in patients with HBeAg-negative chronic hepatitis B infection
Authors: Scott Fung, Mark Sulkowski, Jacob Lalezari, Eugene R. Schiff, Douglas Dieterich, Tarek Hassanein, Paul Kwo, Magdy Elkhashab, Ronald Nahass, Walid Ayoub, Steven-Huy Han, Maurizio Bonacini, Katia Alves, Hany Zayed, Qi Huang, Richard Colonno, Steven Knox, Alnoor Ramji, Michael Bennett, Edward Gane, Natarajan Ravendhran, James Park, Ira Jacobson, Ho Bae, Sing Chan, Hie-Won Hann, Xiaoli Ma, Tuan Nguyen, Man-Fung Yuen
Journal: Journal of Hepatology (2020)
Soundings: Knight duty
Authors: Liam Farrell
Journal: BMJ (2005)

“`Tis the Lady of Shallot,” she said.

“Wouldst thou call upon me?”

“No chance,” I said, “new NHS policy, not efficient use of time, etc etc.”

She was a quick learner. “I sense an ill humour, and central crushing chest pain radiating to my left arm and all.”

“Oh, all right,” I snarled graciously.

I parked outside the tower in a temper, accidentally mowing down a unicorn; rather nouveau riche design, I thought. I walked up a winding stair, admiring the mural of Merlin performing an adenoidectomy on The Green Knight, and tripped on some glistening sticky stuff.

“Mind the web,” said a voice from behind a huge mirror, which I noticed was linked to external security cameras, “it's a bugger to spin.”

“If I'm going to examine you, you'll have to come out,” I said.

“No man may look on me, else the curse come upon me and I perish.”

I drew myself up, feeling rather violated; “I am not a man, madam, I am a doctor. You may consider me an asexual robot, or maybe a mutant.”

A beautiful maiden appeared, garbed in voluminous white, a tad too Miss Havisham for my taste. “Oooh,” she said, “aren't you the handsome young buck.”

My reflection in the mirror revealed a specky, balding person.

“Don't meet many guys, do you?” I said. “Now, what about this chest pain?”

“I confess `twas a mere contrivance,” she said, stroking my bald patch meaningfully. “I grow lonely for male company and I figured, what the heck, GPs have to come out when you call, don't they?”

Her expression suddenly changed. “I don't believe it,” she said peevishly, “you wait a lifetime, and then two guys come along at once.”

On the camera screens I saw a knight in armour, brazen greaves glittering in the sun, his mighty stallion befouling the green sward. “Gotta go,” she said.

I felt rejected; he was tall, handsome, and heroic, but I drive a Mercedes.

Lancelot came running up the stairs. His noble visage was grave and his eyes bugging out. “Come quickly, Doc, the fair maiden...”

“Yeah, I can guess, she's all a-swoon, is she?”

I checked her out; her chest was heaving prettily in the way only a very alert chest can manage.

“It's a bad case of melodrama,” I said.
“Dangling” Accelerated Approvals in Oncology
Authors: Julia A. Beaver, Richard Pazdur
Journal: New England Journal of Medicine (2021)

The FDA recently reevaluated accelerated approvals for 35 oncology indications for anti–programmed death ligand 1 antibodies, revealing that for 10 indications, the required trials did not end up confirming benefit and yet their marketing authorization continued.
Discrimination of COVID‐19 From Inflammation‐Induced Cytokine Storm Syndromes Using Disease‐Related Blood Biomarkers
Authors: Christoph Kessel, Richard Vollenberg, Katja Masjosthusmann, Claas Hinze, Helmut Wittkowski, France Debaugnies, Carole Nagant, Francis Corazza, Frédéric Vély, Gilles Kaplanski, Charlotte Girard‐guyonvarc’h, Cem Gabay, Hartmut Schmidt, Dirk Foell, Phil‐robin Tepasse
Journal: Arthritis & Rheumatology (2021)

Objective Infection with the novel coronavirus SARS–CoV‐2 triggers severe illness with high mortality in a subgroup of patients. Such a critical course of COVID‐19 is thought to be associated with the development of cytokine storm, a condition seen in macrophage activation syndrome (MAS) and secondary hemophagocytic lymphohistiocytosis (HLH). However, specific data demonstrating a clear association of cytokine storm with severe COVID‐19 are still lacking. The aim of this study was to directly address whether immune activation in COVID‐19 does indeed mimic the conditions found in these classic cytokine storm syndromes. Methods Levels of 22 biomarkers were quantified in serum samples from patients with COVID‐19 (n = 30 patients, n = 83 longitudinal samples in total), patients with secondary HLH/MAS (n = 50), and healthy controls (n = 9). Measurements were performed using bead array assays and single‐marker enzyme‐linked immunosorbent assay. Serum biomarker levels were assessed for correlations with disease outcome. Results In patients with secondary HLH/MAS, we observed pronounced activation of the interleukin‐18 (IL‐18)–interferon‐γ axis, increased serum levels of IL‐1 receptor antagonist, intercellular adhesion molecule 1, and IL‐8, and strongly reduced levels of soluble Fas ligand in the course of SARS–CoV‐2 infection. These observations appeared to discriminate immune dysregulation in critical COVID‐19 from the well‐recognized characteristics of other cytokine storm syndromes. Conclusion Serum biomarker profiles clearly separate COVID‐19 from MAS or secondary HLH in terms of distinguishing the severe systemic hyperinflammation that occurs following SARS–CoV‐2 infection. These findings could be useful in determining the efficacy of drugs targeting key molecules and pathways specifically associated with systemic cytokine storm conditions in the treatment of COVID‐19.
Rituximab-induced hypogammaglobulinemia and infection risk in pediatric patients
Authors: Roxane Labrosse, Sara Barmettler, Beata Derfalvi, Annaliesse Blincoe, Guilhem Cros, Jonathan Lacombe-Barrios, Julie Barsalou, Nancy Yang, Nora Alrumayyan, Jan Sinclair, Mei-Sing Ong, Carlos A. Camargo, Jolan Walter, Elie Haddad
Journal: Journal of Allergy and Clinical Immunology (2021)
Translational Nanotherapeutics Reprograms Immune Microenvironment in Malignant Pleural Effusion of Lung Adenocarcinoma
Authors: Zhenhuan Song, Weizhan Luo, Haichong Zheng, Yunxiang Zeng, Jinlin Wang, Tianfeng Chen
Journal: Advanced Healthcare Materials (2021)

Malignant pleural effusion (MPE) remains a treatment bottleneck in advanced lung cancer, due to its complicated microenvironments and "cold" immunity. Therefore, the search for therapeutic drugs to transform MPE to functionally "hot" one could advance the development of effective immunotherapeutic strategy. Herein, translational selenium nanoparticles coated with immune-modulating macromolecule lentinan (SeNPs@LNT) are designed to restore the dysfunctional immune cells in patient-derived MPE microenvironment. Internalization of the SeNPs@LNT can effectively reduce the immunosuppressive status by enhancing the proliferation of CD4+ T cells and natural killer cells, and remodeling the tumor associated macrophages into tumoricidal M1 phenotype in MPE derived from patients presenting low Se levels in blood and pleural effusion. Th1, cytotoxic T cell, γδ T, and B cell functions are upregulated, and Th2, Th17, and Treg cells activity is downregulated. Furthermore, SeNPs@LNT can be gradually metabolized into SeCys2 to promote the production of metabolites associated with tumor growth inhibition and immune response activation in MPE microenvironment. In contrast, lung cancer markers and vitamin B6 metabolism are decreased. The translational SeNP-based nanotherapeutic strategy restores functional "cold" MPE to "hot" MPE to activate the immune responses of various immune cells in MPE of lung cancer patients.
Cervical Cancer Immunotherapy: Facts and Hopes
Authors: Louise Ferrall, Ken Y. Lin, Richard B.S. Roden, Chien-Fu Hung, T.-C. Wu
Journal: Clinical Cancer Research (2021)

Abstract It is a sad fact that despite being almost completely preventable through human papillomavirus (HPV) vaccination and screening, cervical cancer remains the fourth most common cancer to affect women worldwide. Persistent high-risk HPV (hrHPV) infection is the primary etiologic factor for cervical cancer. Upward of 70% of cases are driven by HPV types 16 and 18, with a dozen other hrHPVs associated with the remainder of cases. Current standard-of-care treatments include radiotherapy, chemotherapy, and/or surgical resection. However, they have significant side effects and limited efficacy against advanced disease. There are a few treatment options for recurrent or metastatic cases. Immunotherapy offers new hope, as demonstrated by the recent approval of programmed cell death protein 1–blocking antibody for recurrent or metastatic disease. This might be augmented by combination with antigen-specific immunotherapy approaches, such as vaccines or adoptive cell transfer, to enhance the host cellular immune response targeting HPV-positive cancer cells. As cervical cancer progresses, it can foster an immunosuppressive microenvironment and counteract host anticancer immunity. Thus, approaches to reverse suppressive immune environments and bolster effector T-cell functioning are likely to enhance the success of such cervical cancer immunotherapy. The success of nonspecific immunostimulants like imiquimod against genital warts also suggest the possibility of utilizing these immunotherapeutic strategies in cervical cancer prevention to treat precursor lesions (cervical intraepithelial neoplasia) and persistent hrHPV infections against which the licensed prophylactic HPV vaccines have no efficacy. Here, we review the progress and challenges in the development of immunotherapeutic approaches for the prevention and treatment of cervical cancer.
Interpretable survival prediction for colorectal cancer using deep learning
Authors: Ellery Wulczyn, David F. Steiner, Melissa Moran, Markus Plass, Robert Reihs, Fraser Tan, Isabelle Flament-Auvigne, Trissia Brown, Peter Regitnig, Po-Hsuan Cameron Chen, Narayan Hegde, Apaar Sadhwani, Robert MacDonald, Benny Ayalew, Greg S. Corrado, Lily H. Peng, Daniel Tse, Heimo Müller, Zhaoyang Xu, Yun Liu, Martin C. Stumpe, Kurt Zatloukal, Craig H. Mermel
Journal: npj Digital Medicine (2021)

Deriving interpretable prognostic features from deep-learning-based prognostic histopathology models remains a challenge. In this study, we developed a deep learning system (DLS) for predicting disease specific survival for stage II and III colorectal cancer using 3,652 cases (27,300 slides). When evaluated on two validation datasets containing 1,239 cases (9,340 slides) and 738 cases (7,140 slides) respectively, the DLS achieved a 5-year disease-specific survival AUC of 0.70 (95%CI 0.66-0.73) and 0.69 (95%CI 0.64-0.72), and added significant predictive value to a set of 9 clinicopathologic features. To interpret the DLS, we explored the ability of different human-interpretable features to explain the variance in DLS scores. We observed that clinicopathologic features such as T-category, N-category, and grade explained a small fraction of the variance in DLS scores (R2=18% in both validation sets). Next, we generated human-interpretable histologic features by clustering embeddings from a deep-learning based image-similarity model and showed that they explain the majority of the variance (R2 of 73% to 80%). Furthermore, the clustering-derived feature most strongly associated with high DLS scores was also highly prognostic in isolation. With a distinct visual appearance (poorly differentiated tumor cell clusters adjacent to adipose tissue), this feature was identified by annotators with 87.0-95.5% accuracy. Our approach can be used to explain predictions from a prognostic deep learning model and uncover potentially-novel prognostic features that can be reliably identified by people for future validation studies.
Decreasing Failure-to-Rescue From Severe Maternal Morbidity at Cesarean Delivery
Authors: Koji Matsuo, Rachel S. Mandelbaum, Shinya Matsuzaki, Rauvynne N. Sangara, Richard H. Lee, Maximilian Klar, Joseph G. Ouzounian
Journal: JAMA Surgery (2021)

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Covid-19: Government’s shielding scheme failed thousands of clinically extremely vulnerable people, say MPs
Authors: Elisabeth Mahase
Journal: BMJ (2021)

At the start of the covid-19 pandemic the UK government failed to reach up to 800 000 clinically extremely vulnerable people who had been added to the shielding list, meaning they could not get support such as food parcels, a report by MPs has said.1

The Public Accounts Committee found that nearly half of these people were not reached because of missing or incorrect telephone numbers in NHS records. Local authorities were then asked to contact the people, but the Ministry of Housing, Communities and Local Government still does not know whether the 800 000 people were reached.

The report said, “The programme suffered from the problems of poor data and a lack of joined-up systems that we see all too …