tbuckley/cabot-search huggingface dataset:
The National Cardiovascular Data Registry Data Quality Program 2020
Authors: David J. Malenka, Deepak L. Bhatt, Steven M. Bradley, David M. Shahian, Jasmine Draoui, Claire A. Segawa, Christina Koutras, Jinnette D. Abbott, James C. Blankenship, Robert Vincent, John Windle, Thomas T. Tsai, Jeptha Curtis, Matthew Roe, Frederick A. Masoudi
Journal: Journal of the American College of Cardiology (2022)
RE: Nitrogen-Based Bisphosphonate Use and Ovarian Cancer Risk in Women Aged 50 Years and Older
Authors: Steven Lehrer, Peter H Rheinstein
Journal: JNCI Journal of the National Cancer Institute (2022)

Tuesley et al.(1) report that among women aged older than 50 years, use of nitrogen-based bisphosphonates was associated with reduced epithelial ovarian cancer risk, with an almost 50% lower risk of the endometrioid histotype, and a 16% lower risk of serous cancers.However, in a previous meta-analysis of 6783 ovarian cancer cases (4 studies with 105 507 participants), the reduction in risk associated with bisphosphonates was not statistically significant (2).We used data from UK Biobank to assess the association of bisphosphonates with epithelial ovarian cancer.The UK Biobank is a large prospective observational study of men and women (3).This methodology is like that of the ongoing Framingham Heart Study (4), with the exception that the UKB program collects postmortem samples, which Framingham did not.Our UK Biobank application was approved as UKB project 57245 (SL, PHR).Participants were recruited from across 22 centers located throughout England, Wales, and Scotland between 2006 and 2010 and continue to be longitudinally followed up for capture of subsequent health events.Bisphosphonate use was from UKB category 100075, Medications, verbal interview by a trained nurse on prescription medications, including data on type and number of medications taken.Patients with ovarian cancer were identified with ICD10 C56, malignant neoplasm of the ovary.Data processing was performed on Minerva, a Linux mainframe with Centos 7.6, at the Icahn School of Medicine at Mount Sinai.We used the UK Biobank Data Parser (ukbb parser), a python-based package that allows easy interfacing with the large UK Biobank dataset (5).SPSS v 26 was used for statistical analysis.The cutpoint for statistical significance (P) was less than .05.
Incorrect Trial Registration Identifier
Journal: JAMA Network Open (2022)

Thomas G. H. Kempen, MPharm; Maria Bertilsson, MSc; Nermin Hadziosmanovic, MSc; Karl-Johan Lindner, MPharm, PhD; Håkan Melhus, MD, PhD; Elisabet I. Nielsen, MPharm, PhD; Johanna Sulku, MPharm; Ulrika Gillespie, MPharm, PhD
Molecular biomarker-defined brain tumors: Epidemiology, validity, and completeness in the United States
Authors: J Bryan Iorgulescu, Chuxuan Sun, Corey Neff, Gino Cioffi, Catherine Gutierrez, Carol Kruchko, Jennifer Ruhl, Kristin A Waite, Serban Negoita, Jim Hofferkamp, Tarik Tihan, Roger McLendon, Daniel J Brat, Quinn T Ostrom, Jill S Barnholtz-Sloan
Journal: Neuro-Oncology (2022)

Selected molecular biomarkers were incorporated into the US cancer registry reporting for patients with brain tumors beginning in 2018. We investigated the completeness and validity of these variables and described the epidemiology of molecularly defined brain tumor types.
JAK inhibitors and COVID-19
Authors: Gabriel Levy, Paola Guglielmelli, Peter Langmuir, Stefan N Constantinescu
Journal: Journal for ImmunoTherapy of Cancer (2022)

During SARS-CoV-2 infection, the innate immune response can be inhibited or delayed, and the subsequent persistent viral replication can induce emergency signals that may culminate in a cytokine storm contributing to the severe evolution of COVID-19. Cytokines are key regulators of the immune response and virus clearance, and, as such, are linked to the—possibly altered—response to the SARS-CoV-2. They act via a family of more than 40 transmembrane receptors that are coupled to one or several of the 4 Janus kinases (JAKs) coded by the human genome, namely JAK1, JAK2, JAK3, and TYK2. Once activated, JAKs act on pathways for either survival, proliferation, differentiation, immune regulation or, in the case of type I interferons, antiviral and antiproliferative effects. Studies of graft-versus-host and systemic rheumatic diseases indicated that JAK inhibitors (JAKi) exert immunosuppressive effects that are non-redundant with those of corticotherapy. Therefore, they hold the potential to cut-off pathological reactions in COVID-19. Significant clinical experience already exists with several JAKi in COVID-19, such as baricitinib, ruxolitinib, tofacitinib, and nezulcitinib, which were suggested by a meta-analysis (Patoulias et al. ) to exert a benefit in terms of risk reduction concerning major outcomes when added to standard of care in patients with COVID-19. Yet, only baricitinib is recommended in first line for severe COVID-19 treatment by the WHO, as it is the only JAKi that has proven efficient to reduce mortality in individual randomized clinical trials (RCT), especially the Adaptive COVID-19 Treatment Trial (ACTT-2) and COV-BARRIER phase 3 trials. As for secondary effects of JAKi treatment, the main caution with baricitinib consists in the induced immunosuppression as long-term side effects should not be an issue in patients treated for COVID-19. We discuss whether a class effect of JAKi may be emerging in COVID-19 treatment, although at the moment the convincing data are for baricitinib only. Given the key role of JAK1 in both type I IFN action and signaling by cytokines involved in pathogenic effects, establishing the precise timing of treatment will be very important in future trials, along with the control of viral replication by associating antiviral molecules.
Selective estrogen receptor modulators contribute to prostate cancer treatment by regulating the tumor immune microenvironment
Authors: Dali Tong
Journal: Journal for ImmunoTherapy of Cancer (2022)

Prostate cancer (PC) has previously been established as a cold tumor and develops in an inert immunosuppressive environment. Current research focuses on altering the immune microenvironment of PC from cold to hot; thus, in the present review, the diverse roles of estrogen and estrogen receptor (ER) signaling was examined in the tumor cell and tumor immune microenvironment (TIM). We hypothesized that ERα promotes PC progression and ERβ impedes epithelial-mesenchymal transition in PC cells, while in the TIM, ERβ mediates the immunosuppressive environment, and low levels of ERα is associated with disease development. Selective estrogen receptor modulators (SERMs) or selective ER degraders play diverse roles in the regulation of ER isoforms. Patients with PC may benefit from the use of SERMs, including raloxifene, in combination with anti-PD1/PD-L1 checkpoint immunotherapy, or TGF-β or Wnt antagonists. The present review demonstrated that immunotherapy-based strategies combined with SERMs may be an option for the future of PC-targeting therapy.
Annals Graphic Medicine - Dr. Mom: Stickers to Add to Your Annual Review
Authors: Grace E. Farris
Journal: Annals of Internal Medicine (2022)

Web ExclusivesApril 2022Annals Graphic Medicine - Dr. Mom: Stickers to Add to Your Annual ReviewFREEGrace E. Farris, MDGrace E. Farris, MDUniversity of Texas, Austin, Texas (G.E.F.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G22-0017 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Donna Sue Dolle, MDN/A21 March 2022 Ugh If this were all I'm graded on, I'm outta here. There is much more to taking good care of patients than checking boxes others impose on me. Disclosures: Clear Lake Internal Medicine Author, Article, and Disclosure InformationAffiliations: University of Texas, Austin, Texas (G.E.F.)Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G21-0024.Author/Illustrator Information: Grace E. Farris, MD, is an assistant professor of medicine at Dell Medical School at the University of Texas in Austin, Texas. You can view her work at her website: www.farrisgrace.com.About Dr. Mom: In Dr. Mom, physician and cartoonist Grace Farris examines work–life balance while mothering and doctoring. Dr. Mom appears monthly in Annals Graphic Medicine at Annals.org.This article was published at Annals.org on 22 March 2022. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics April 2022Volume 175, Issue 4Page: W49-W50 ePublished: 22 March 2022 Issue Published: April 2022 Copyright & PermissionsCopyright © 2022 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Covid-19: US sees increase in sexually transmitted diseases and teen drug overdose deaths
Authors: Janice Hopkins Tanne
Journal: BMJ (2022)

Covid-19: US sees increase in sexually transmitted diseases and teen drug overdose deaths Janice Hopkins TanneThe prevalence of sexually transmitted diseases (STDs) and deaths from drug overdoses increased in the US over the past two years, showing the pandemic's effect on public health.1 Centers for Disease Control and Prevention.Sexually transmitted disease surveillance 2020.www.cdc.gov/std/statistics/2020/default.htm 2 Centers for Disease Control and Prevention.New data suggest STDs continued to increase during first year of the covid-19 pandemic.12 April 2022.
B cell receptor signaling strength modulates cancer immunity
Authors: Jian Ye, Peter P. Lee
Journal: Journal of Clinical Investigation (2022)

Tumor-infiltrating B cells exert antitumor effects by producing antibodies against tumor-associated antigens. Conversely, B cells may promote tumors through the production of factors that dampen antitumor immunity. In this issue of the JCI, Bing Yang, Zhen Zhang, et al. investigated the roles of B cell receptor (BCR) signaling in antitumor immunity, focusing on the role of an Asia-specific variant of human immunoglobulin G1 (IgG1) containing a Gly396 to Arg396 substitution (hIgG1-G396R) in colorectal cancer (CRC). Epidemiological analysis revealed an association between hIgG1-G396R and progression-free survival in CRC. Human samples and mouse models of CRC showed plasma cells, as opposed to B cells, infiltrating the tumor microenvironment. Notably, patients with the hIgG1-G396R variant had increased CD8+ T cells, dendritic cells, and tertiary lymphoid structure density. These findings indicate that the hIgG1-G396R variant represses tumorigenesis by enhancing B cell responses, and suggest that modulating BCR signaling could improve the efficacy of immunotherapy in cancer.
Tip of the iceberg: A comprehensive review of liver disease in Inborn errors of immunity
Authors: Disha Sharma, Gil Ben Yakov, Devika Kapuria, Gracia Viana Rodriguez, Meital Gewirtz, James Haddad, David E. Kleiner, Christopher Koh, Jenna R. E. Bergerson, Alexandra F. Freeman, Theo Heller
Journal: Hepatology (2022)

Abstract Inborn errors of immunity (IEIs) consist of numerous rare, inherited defects of the immune system that affect about 500,000 people in the United States. As advancements in diagnosis through genetic testing and treatment with targeted immunotherapy and bone marrow transplant emerge, increasing numbers of patients survive into adulthood posing fresh clinical challenges. A large spectrum of hepatobiliary diseases now present in those with immunodeficiency diseases, leading to morbidity and mortality in this population. Awareness of these hepatobiliary diseases has lagged the improved management of the underlying disorders, leading to missed opportunities to improve clinical outcomes. This review article provides a detailed description of specific liver diseases occurring in various inborn errors of immunity. A generalized approach to diagnosis and management of hepatic complications is provided, and collaboration with hepatologists, immunologists, and pathologists is emphasized as a requirement for optimizing management and outcomes.
Albumin and interferon-β fusion protein serves as an effective vaccine adjuvant to enhance antigen-specific CD8+ T cell-mediated antitumor immunity
Authors: Ssu-Hsueh Tseng, Max A Cheng, Emily Farmer, Louise Ferrall, Yu Jui Kung, Brandon Lam, Ling Lim, T-C Wu, Chien-Fu Hung
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Type I interferons (IFN) promote dendritic cells maturation and subsequently enhance generation of antigen-specific CD8 +T cell for the control of tumor. Using type I interferons as an adjuvant to vaccination could prove to be a potent strategy. However, type I interferons have a short half-life. Albumin linked to a protein will prolong the half-life of the linked protein. Methods In this study, we explored the fusion of albumin to IFNβ (Alb-IFNβ) for its functional activity both in vitro and in vivo. We determined the half-life of Alb-IFNβ following treatment in the serum, tumor, and tumor draining lymph nodes in both wild type and FcRn knockout mice. We characterized the ability of Alb-IFNβ to enhance antigen-specific CD8+ T cells using ovalbumin (OVA) or human papillomavirus (HPV) E7 long peptides. Next, we evaluated the therapeutic antitumor effect of coadministration of AlbIFNβ with antigenic peptides against HPVE7 expressing tumor and the treatment’s ability to generate HPVE7 antigen specific CD8+ T cells. The contribution of the antitumor effect by lymphocytes was also examined by an antibody depletion experiment. The ability of Alb-IFNβ to serve as an adjuvant was tested using clinical grade therapeutic protein-based HPV vaccine, TACIN. Results Alb-IFNβ retains biological function and does not alter the biological activity of IFNβ. In addition, Alb-IFNβ extends half-life of IFNβ in serum, lymph nodes and tumor. The coadministration of Alb-IFNβ with OVA or HPVE7 antigenic peptides enhances antigen-specific CD8 +T cell immunity, and in a TC-1 tumor model results in a significant therapeutic antitumor effect. We found that CD8 +T cells and dendritic cells, but not CD4 +T cells, are important for the observed antitumor therapeutic effect mediated by Alb-IFNβ. Finally, Alb-IFNβ served as a potent adjuvant for TA-CIN for the treatment of HPV antigen expressing tumors. Conclusions Overall, Alb-IFNβ serves as a potent adjuvant for enhancement of strong antigen-specific CD8 +T cell antitumor immunity, reduction of tumor burden, and increase in overall survival. Alb-IFNβ potentially can serve as an innovative adjuvant for the development of vaccines for the control of infectious disease and cancer.
Smart Shape‐Memory Polymeric String for the Contraction of Blood Vessels in Fetal Surgery of Sacrococcygeal Teratoma
Authors: Ailifeire Fulati, Koichiro Uto, Masanobu Iwanaga, Miho Watanabe, Mitsuhiro Ebara
Journal: Advanced Healthcare Materials (2022)

Shape-memory polymers (SMPs) are promising materials in numerous emerging biomedical applications owing to their unique shape-memory characteristics. However, simultaneous realization of high strength, toughness, stretchability while maintaining high shape fixity (Rf ) and shape recovery ratio (Rr ) remains a challenge that hinders their practical applications. Herein, a novel shape-memory polymeric string (SMP string) that is ultra-stretchable (up to 1570%), strong (up to 345 MPa), tough (up to 237.9 MJ m-3 ), and highly recoverable (Rf averagely above 99.5%, Rr averagely above 99.1%) through a facile approach fabricated solely by tetra-branched poly(ε-caprolactone) (PCL) is reported. Notably, the shape-memory contraction force (up to 7.97 N) of this SMP string is customizable with the manipulation of their energy storage capacity by adjusting the string thickness and stretchability. In addition, this SMP string displays a controllable shape-memory response time and demonstrates excellent shape-memory-induced contraction effect against both rigid silicone tubes and porcine carotids. This novel SMP string is envisioned to be applied in the contraction of blood vessels and resolves the difficulties in the restriction of blood flow in minimally invasive surgeries such as fetoscopic surgery of sacrococcygeal teratoma (SCT).
OrienX010, an oncolytic virus, in patients with unresectable stage IIIC–IV melanoma: a phase Ib study
Authors: ChuanLiang Cui, Xuan Wang, Bin Lian, Qing Ji, Li Zhou, Zhihong Chi, Lu Si, Xinan Sheng, Yan Kong, Jiayi Yu, Siming Li, Lili Mao, Bixia Tang, Jie Dai, Xieqiao Yan, Xue Bai, Robert Andtbacka, Jun Guo
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Melanoma in people of Asian descent presents primarily in non-sun-exposed areas, such as acral and mucosal melanoma. Compared with the predominant sun-exposed area melanomas in Caucasians, acral and mucosal melanomas do not respond as well to immunotherapy and are associated with a worse prognosis. Hence, there is an urgent need for improved treatment for melanoma in Asians. This phase Ib trial evaluated the safety and efficacy of the modified herpes simplex virus-1 oncolytic virus OrienX010 in Chinese patients with unresectable stage IIIC–IV melanoma. Methods Patients were treated in two different cohorts. In cohort 08 (n=12), patients received up to 5 mL of 8×10 7 pfu/mL OrienX010 intratumoral injections every 2 weeks until disease progression and responses were evaluated every 6 weeks. In cohort 09 (n=14), patients received up to 10 mL of 8×10 7 pfu/mL OrienX010 intratumoral injections and responses were evaluated every 8 weeks. Results Between June 2014 and May 2017, 26 patients were enrolled, including 18 (69.2%) patients with acral melanoma. Fever and injection site reaction were the most frequent adverse events. Only one patient experienced a grade ≥3 adverse event and no dose-limiting toxicities were observed. The objective response rate was 19.2% and the disease control rate was 53.8%. The median duration of response was 6.0 months. Antitumor effects were observed in 54.6% of injected lesions and 48.8% of non-injected lesions, including one (16.7%) of six evaluable distant lung metastases. The median progression-free survival was 2.9 months and overall survival was 19.2 months. Compared with patients treated in cohort 08, patients treated in cohort 09 had an improved objective response rate (28.6% vs 8.3%) and a median progression-free survival of 3.0 months vs 2.8 months. Conclusions OrienX010 oncolytic virotherapy has a tolerable safety profile with antitumor effects in both injected and non-injected metastases and warrants further evaluation in patients with melanoma. Based on these results, the higher cohort 09 dose (up to 10 mL of 8×10 7 pfu/mL every 2 weeks) was selected as the recommended phase II dose for ongoing trials. Trial registration number CTR20140631 (cohort 08), CTR20150881 (cohort 09).
Impact of Polyvascular Disease and Diabetes on Limb and Cardiovascular Risk in Peripheral Artery Disease
Authors: Sean A. Behan, Hillary Mulder, Frank W. Rockhold, J. Antonio Gutierrez, Iris Baumgartner, Brian G. Katona, Kenneth W. Mahaffey, Lars Norgren, W. Schuyler Jones, Marc P. Bonaca
Journal: Journal of the American College of Cardiology (2022)
Night Light
Authors: Rae Varcoe
Journal: Annals of Internal Medicine (2022)

Ad LibitumApril 2022Night LightRae Varcoe, MA, MB ChBRae Varcoe, MA, MB ChBNelson, New ZealandSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M21-4147 Audio Reading - “Night Light” Audio. Virginia L. Hood, MD, a physician from the University of Vermont, reads “Night Light” by Rae Varcoe, MA, MB ChB Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail the ghosts of former patientswander the oncology wards by nightthey are sure of their waythey know each lino tile, each drip stand,each stiff enclosing curtainthey audit the peaks of the temperature chartsthey are amused by the notes of the medical staffthey wish prescribers accuracy and effectivenessthey observe the lists, they examine the lockersthe voices sounding from the TVremind them how alone they were,how lonelybefore they leavethey wash their hands Author, Article, and Disclosure InformationAffiliations: Nelson, New ZealandCorresponding Author: Rae Varcoe, MA, MB ChB; e-mail, [email protected]com. PreviousarticleNextarticle Advertisement Audio Reading - “Night Light” Audio. Virginia L. Hood, MD, a physician from the University of Vermont, reads “Night Light” by Rae Varcoe, MA, MB ChB Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics April 2022Volume 175, Issue 4Page: 615 ePublished: 19 April 2022 Issue Published: April 2022 Copyright & PermissionsCopyright © 2022 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
HOXB13 suppresses de novo lipogenesis through HDAC3-mediated epigenetic reprogramming in prostate cancer
Authors: Xiaodong Lu, Ka-wing Fong, Galina Gritsina, Fang Wang, Sylvan C. Baca, Lourdes T. Brea, Jacob E. Berchuck, Sandor Spisak, Jenny Ross, Colm Morrissey, Eva Corey, Navdeep S. Chandel, William J. Catalona, Ximing Yang, Matthew L. Freedman, Jonathan C. Zhao, Jindan Yu
Journal: Nature Genetics (2022)
Bronchopulmonary dysplasia and expiratory airflow at 8 years in children born extremely preterm in the post-surfactant era
Authors: Lex William Doyle, Sarath Ranganathan, Jeanie Cheong
Journal: Thorax (2022)

It is unclear if bronchopulmonary dysplasia (BPD) is independently associated with reduced expiratory airflow at school age.To determine the independent associations of moderate-severe BPD, mild BPD, gestational age and birth weight z-score with expiratory airflow in children born extremely preterm (EP; <28 weeks' gestation).All EP survivors born in Victoria, Australia, in three eras (1991-1992, n=225; 1997, n=151; and 2005, n=170) were recruited at birth and 418/546 (77%) had valid spirometry data at 8 years. BPD was classified as moderate-severe (oxygen requirement at 36 weeks' postmenstrual age), or mild (oxygen >28 days but not at 36 weeks' postmenstrual age). Expiratory airflow variables, including the forced expired volume in 1 s (FEV1), were measured and values converted to z-scores.Compared with no BPD (n=94), moderate-severe BPD (n=193) was associated with a substantial reduction in expiratory airflow (eg, zFEV1 mean difference -0.69, 95% CI -0.97 to -0.41; p<0.001), but mild BPD (n=131) was not (zFEV1 mean difference 0.01, 95% CI -0.28 to 0.31; p=0.93). On multivariable analysis, moderate-severe BPD remained strongly associated with reduced airflow (zFEV1 mean difference -0.63, 95% CI -0.92 to -0.33; p<0.001), but mild BPD (zFEV1 mean difference 0.04, 95% CI -0.26 to 0.34; p=0.27), gestational age (zFEV1 0.06 mean increase per week, 95% CI -0.05 to 0.17; p=0.29) and birth weight z-score (zFEV1 0.07 mean increase per SD, 95% CI -0.06 to 0.20; p=0.28) were not.In children born EP, moderate-severe BPD, but not mild BPD was independently associated with reduced expiratory airflow at 8 years.
Association of the COVID-19 Pandemic With Rates of Prostate Cancer Biopsies and Diagnoses in Black vs White US Veterans
Authors: Zachary Klaassen, Shannon Stock, Justin Waller, Amanda De Hoedt, Stephen J. Freedland
Journal: JAMA Oncology (2022)

Several studies have assessed the negative effect of the COVID-19 pandemic on cancer screening and diagnosis rates. However, this has not been evaluated for prostate biopsy and prostate cancer (PC) diagnosis in an equal-access health care system.