tbuckley/cabot-search huggingface dataset:
GP consultation rates for sequelae after acute covid-19 in patients managed in the community or hospital in the UK: population based study
Authors: Hannah R Whittaker, Claudia Gulea, Ardita Koteci, Constantinos Kallis, Ann D Morgan, Chukwuma Iwundu, Mark Weeks, Rikisha Gupta, Jennifer K Quint
Journal: BMJ (2021)

To describe the rates for consulting a general practitioner (GP) for sequelae after acute covid-19 in patients admitted to hospital with covid-19 and those managed in the community, and to determine how the rates change over time for patients in the community and after vaccination for covid-19.
Differentiation therapy for myeloid malignancies: beyond cytotoxicity
Authors: Ryan J. Stubbins, Aly Karsan
Journal: Blood Cancer Journal (2021)

Abstract Blocked cellular differentiation is a central pathologic feature of the myeloid malignancies, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Treatment regimens promoting differentiation have resulted in incredible cure rates in certain AML subtypes, such as acute promyelocytic leukemia. Over the past several years, we have seen many new therapies for MDS/AML enter clinical practice, including epigenetic therapies (e.g., 5-azacitidine), isocitrate dehydrogenase (IDH) inhibitors, fms-like kinase 3 (FLT3) inhibitors, and lenalidomide for deletion 5q (del5q) MDS. Despite not being developed with the intent of manipulating differentiation, induction of differentiation is a major mechanism by which several of these novel agents function. In this review, we examine the new therapeutic landscape for these diseases, focusing on the role of hematopoietic differentiation and the impact of inflammation and aging. We review how current therapies in MDS/AML promote differentiation as a part of their therapeutic effect, and the cellular mechanisms by which this occurs. We then outline potential novel avenues to achieve differentiation in the myeloid malignancies for therapeutic purposes. This emerging body of knowledge about the importance of relieving differentiation blockade with anti-neoplastic therapies is important to understand how current novel agents function and may open avenues to developing new treatments that explicitly target cellular differentiation. Moving beyond cytotoxic agents has the potential to open new and unexpected avenues in the treatment of myeloid malignancies, hopefully providing more efficacy with reduced toxicity.
Abstract 9086: Sex Differences in the Association Between Bystander CPR and Survival for Patients With Out-of-Hospital Cardiac Arrest
Authors: Kiok Ahn, Bryan McNally, Paul Chan
Journal: Circulation (2021)

Background: Bystander cardiopulmonary resuscitation (CPR) is associated with a better survival outcome in patients with out-of-hospital cardiac arrest (OHCA). However, there may be cultural barriers in performing high-quality bystander CPR in women in some non-Western countries and the effect of bystander CPR on survival outcomes may differ by patients’ sex. Methods: Using data between 2012-2018 from a national OHCA registry from the Republic of Korea, we identified adult patients with OHCA of presumed cardiac etiology. The main exposures were bystander CPR and patients’ sex. The primary outcome was survival discharge and the secondary outcome was favorable neurological survival. Multivariable logistic regression evaluated the association between bystander CPR and survival, adjusted for patients’ age, sex, socio-economic status, year of arrest, witnessed arrest status, initial OHCA rhythm, location of arrest, urbanization level of arrest location, and type of bystander. The interaction between bystander CPR and sex was explicitly evaluated in the models. Results: Of 101,505 patients with OHCA in the cohort, 34,124 (33.6 %) were women and 67,381 (64.4 %) were men. Bystander CPR was performed on 18,481 (54.2%) women and 35,904 (53.3%) men (p=0.07). Unadjusted rates of survival discharge were 4.5% in women and 9.5 % in men (p&lt;0.001), and rates of favorable neurological survival were 2.5% in women and 6.4% in men (p&lt;0.001). In multivariable logistic regression models, there was a significant interaction (p=0.005) between bystander CPR and sex for survival to discharge, with an adjusted OR for bystander CPR of 1.16 (95% CI: 1.08-1.23) in men and 0.91 (95% CI: 0.80-1.02) in women. For favorable neurological survival, there was also a significant interaction (p=0.01) between sex and bystander CPR, with an adjusted OR for bystander CPR of 1.47 (95% CI: 1.36-1.60) in men and 1.16 (95% CI: 0.98- 1.37) in women. Conclusions: In a national registry of OHCA from the Republic of Korea, men who received bystander CPR were more likely to survive whereas women who received bystander CPR were not.
Harnessing the Natural Healing Power of Colostrum: Bovine Milk‐Derived Extracellular Vesicles from Colostrum Facilitating the Transition from Inflammation to Tissue Regeneration for Accelerating Cutaneous Wound Healing
Authors: Hyosuk Kim, Da Eun Kim, Geonhee Han, Nu Ri Lim, Eun Hye Kim, Yeongji Jang, Haeun Cho, Hochung Jang, Ki Hun Kim, Sun Hwa Kim, Yoosoo Yang
Journal: Advanced Healthcare Materials (2021)

As wound healing is an extremely complicated process, consisting of a cascade of interlocking biological events, successful wound healing requires a multifaceted approach to support appropriate and rapid transitions from the inflammatory to proliferative and remodeling phases. In this regard, here the potential use of bovine milk extracellular vesicles (EVs) to enhance wound healing is investigated. The results show that milk EVs promote fibroblast proliferation, migration, and endothelial tube formation. In particular, milk EVs derived from colostrum (Colos EVs) contain various anti-inflammatory factors facilitating the transition from inflammation to proliferation phase, as well as factors for tissue remodeling and angiogenesis. In an excisional wound mouse model, Colos EVs promote re-epithelialization, activate angiogenesis, and enhance extracellular matrix maturation. Interestingly, Colos EVs are further found to be quite resistant to freeze-drying procedures, maintaining their original characteristics and efficacy for wound repair after lyophilization. These findings on the superior stability and excellent activity of milk Colos EVs indicate that they hold great promise to be developed as anti-inflammatory therapeutics, especially for the treatment of cutaneous wounds.
B Cells and Tertiary Lymphoid Structures: Friends or Foes in Cancer Immunotherapy?
Authors: Martin Lauss, Marco Donia, Inge Marie Svane, Göran Jönsson
Journal: Clinical Cancer Research (2021)

Tumor cells pose a challenge to the adaptive immune system, and its key cell types, T and B cells, have frequently been associated with an improved prognosis. The success of immune checkpoint blockade has confirmed the relevance of T cells. However, the role of B cells is increasingly recognized, and highlighted in this review. Recent data suggest that tumors contain a diverse set of B cells reflecting different developmental states and exerting functions such as antigen presentation, antibody production, and regulatory effects. Further, B cells are frequently located in tertiary lymphoid structures (TLS), which are immune cell niches that sustain an immune response at sites of chronic inflammation. TLSs in tumors display substantial heterogeneity, ranging from cell aggregates to mature structures with an active germinal center. Recent studies have provided insights into initiation, cellular and spatial composition, and function of TLS in a variety of cancer types; however, several critical issues still need to be resolved. Currently, initial reports are discerning the role of TLSs in immunotherapy, with the majority of studies observing TLSs to confer favorable patient outcome. Finally, TLS induction in tumors is evaluated, with the therapeutic aim to reactivate the host immune response.
Comprehensive omics analyses profile genesets related with tumor heterogeneity of multifocal glioblastomas and reveal LIF/CCL2 as biomarkers for mesenchymal subtype
Authors: Sheng-Qing Lv, Zhen Fu, Lin Yang, Qing-Rui Li, Jiang Zhu, Qu-Jing Gai, Min Mao, Jiang He, Yan Qin, Xiao-Xue Yao, Xi Lan, Yan-Xia Wang, Hui-Min Lu, Yan Xiang, Zuo-Xin Zhang, Guo-Hao Huang, Wei Yang, Ping Kang, Zhijian Sun, Yu Shi, Xiao-Hong Yao, Xiu-Wu Bian, Yan Wang
Journal: Theranostics (2021)

Rationale: Around 10%-20% patients with glioblastoma (GBM) are diagnosed with more than one tumor lesions or multifocal GBM (mGBM). However, the understanding on genetic, DNA methylomic, and transcriptomic characteristics of mGBM is still limited. Methods: In this study, we collected nine tumor foci from three mGBM patients followed by whole genome sequencing, whole genome bisulfite sequencing, RNA sequencing, and immunohistochemistry. The data were further examined using public GBM databases and GBM cell line. Results: Analysis on genetic data confirmed common features of GBM, including gain of chr.7 and loss of chr.10, loss of critical tumor suppressors, high frequency of PDGFA and EGFR amplification. Through profiling DNA methylome of individual tumor foci, we found that promoter methylation status of genes involved in detection of chemical stimulus, immune response, and Hippo/YAP1 pathway was significantly changed in mGBM. Although both CNV and promoter methylation alteration were involved in heterogeneity of different tumor foci from same patients, more CNV events than promoter hypomethylation events were shared by different tumor foci, implying CNV were relatively earlier than promoter methylation alteration during evolution of different tumor foci from same mGBM. Moreover, different tumor foci from same mGBM assumed different molecular subtypes and mesenchymal subtype was prevalent in mGBM, which might explain the worse prognosis of mGBM than single GBM. Interestingly, we noticed that LIF and CCL2 was tightly correlated with mesenchymal subtype tumor focus in mGBM and predicted poor survival of GBM patients. Treatment with LIF and CCL2 produced mesenchymal-like transcriptome in GBM cells. Conclusions: Together, our work herein comprehensively profiled multi-omics features of mGBM and emphasized that components of extracellular microenvironment, such as LIF and CCL2, contributed to the evolution and prognosis of tumor foci in mGBM patients.
Comparison of the treatment guidelines for sarcoidosis: common sense in the search for evidence
Authors: Vivienne Kahlmann, Catharina C. Moor, Jelle R. Miedema, Marlies S. Wijsenbeek
Journal: European Respiratory Journal (2021)

<b>A perspective on the recently published ERS clinical practice guideline on treatment of sarcoidosis: although knowledge of the pathogenesis of sarcoidosis has improved, this has not yet translated into better evidence-based therapies</b>https://bit.ly/3qaBIpg
Risks of myocarditis, pericarditis, and cardiac arrhythmias associated with COVID-19 vaccination or SARS-CoV-2 infection
Authors: Martina Patone, Xue W. Mei, Lahiru Handunnetthi, Sharon Dixon, Francesco Zaccardi, Manu Shankar-Hari, Peter Watkinson, Kamlesh Khunti, Anthony Harnden, Carol A. C. Coupland, Keith M. Channon, Nicholas L. Mills, Aziz Sheikh, Julia Hippisley-Cox
Journal: Nature Medicine (2021)

Abstract Although myocarditis and pericarditis were not observed as adverse events in coronavirus disease 2019 (COVID-19) vaccine trials, there have been numerous reports of suspected cases following vaccination in the general population. We undertook a self-controlled case series study of people aged 16 or older vaccinated for COVID-19 in England between 1 December 2020 and 24 August 2021 to investigate hospital admission or death from myocarditis, pericarditis and cardiac arrhythmias in the 1–28 days following adenovirus (ChAdOx1, n = 20,615,911) or messenger RNA-based (BNT162b2, n = 16,993,389; mRNA-1273, n = 1,006,191) vaccines or a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive test ( n = 3,028,867). We found increased risks of myocarditis associated with the first dose of ChAdOx1 and BNT162b2 vaccines and the first and second doses of the mRNA-1273 vaccine over the 1–28 days postvaccination period, and after a SARS-CoV-2 positive test. We estimated an extra two (95% confidence interval (CI) 0, 3), one (95% CI 0, 2) and six (95% CI 2, 8) myocarditis events per 1 million people vaccinated with ChAdOx1, BNT162b2 and mRNA-1273, respectively, in the 28 days following a first dose and an extra ten (95% CI 7, 11) myocarditis events per 1 million vaccinated in the 28 days after a second dose of mRNA-1273. This compares with an extra 40 (95% CI 38, 41) myocarditis events per 1 million patients in the 28 days following a SARS-CoV-2 positive test. We also observed increased risks of pericarditis and cardiac arrhythmias following a positive SARS-CoV-2 test. Similar associations were not observed with any of the COVID-19 vaccines, apart from an increased risk of arrhythmia following a second dose of mRNA-1273. Subgroup analyses by age showed the increased risk of myocarditis associated with the two mRNA vaccines was present only in those younger than 40.
21P Predictive immunological markers of anti-PD-1/PD-L1 therapy efficacy in non-small cell lung cancer
Authors: A.A. Musaelyan, S.V. Lapin, M.A. Urtenova, I.V. Chistyakov, V.D. Nazarov, A.L. Akopov, S.V. Orlov
Journal: Annals of Oncology (2021)
Arterial Chemotherapy of Oxaliplatin Plus Fluorouracil Versus Sorafenib in Advanced Hepatocellular Carcinoma: A Biomolecular Exploratory, Randomized, Phase III Trial (FOHAIC-1)
Authors: Ning Lyu, Xun Wang, Ji-Bin Li, Jin-Fa Lai, Qi-Feng Chen, Shao-Long Li, Hai-Jing Deng, Meng He, Lu-Wen Mu, Ming Zhao
Journal: Journal of Clinical Oncology (2021)

Interventional hepatic arterial infusion chemotherapy of infusional fluorouracil, leucovorin, and oxaliplatin (HAIC-FO) displayed an encouraging safety profile and antitumor activity in a previous phase II trial and a propensity-score-matching study involving patients with locally advanced hepatocellular carcinoma (HCC).In this open-label, phase III trial, patients with advanced HCC, previously untreated with systemic therapy, were randomly assigned in a 1:1 ratio to receive HAIC-FO or sorafenib. The primary end point was overall survival (OS) in the intention-to-treat population. An exploratory model for predicting the efficacy of HAIC-FO on the basis of genomic sequencing was developed.Between May 2017 and May 2020, 262 patients were randomly assigned. The median tumor size was 11.2 cm (interquartile range, 8.5-13.7 cm). Macrovascular invasion was present in 65.6%, and the percentage of patients with > 50% tumor volume involvement of the liver and/or Vp-4 portal vein tumor thrombosis was 49.2%. At data cutoff (October 31, 2020), median OS was 13.9 months for HAIC-FO and 8.2 for sorafenib (hazard ratio [HR] 0.408; 95% CI, 0.301 to 0.552; P < .001). Tumor downstaging occurred in 16 (12.3% of 130) patients receiving HAIC-FO, including 15 receiving curative surgery or ablation, and finally achieving a median OS of 20.8 months, with a 1-year OS rate of 93.8%. In high-risk subpopulations, OS was significantly longer with HAIC-FO than with sorafenib (10.8 months v 5.7 months; HR 0.343; 95% CI, 0.219 to 0.538; P < .001). A newly developed 15-mutant-gene prediction model identified 83% of patients with response to HAIC-FO. HAIC-FO responders had longer OS than HAIC-FO nonresponders (19.3 months v 10.6 months; HR 0.323; 95% CI, 0.186 to 0.560; P = .002).HAIC-FO achieved better survival outcomes than sorafenib in advanced HCC, even in association with a high intrahepatic disease burden.
When Only Words Are Left
Authors: Joseph M. Geskey
Journal: Annals of Internal Medicine (2021)

On Being a DoctorDecember 2021When Only Words Are LeftJoseph M. Geskey, DO, MBA, MS-PopHJoseph M. Geskey, DO, MBA, MS-PopHDublin, OhioSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M21-3424 Audio Reading - “When Only Words Are Left” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads “When Only Words Are Left” by Joseph M. Geskey, DO, MBA, MS-PopH 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 I spent more time with my father over the last few months of his life than I did in over a decade. Long-distance phone calls that mainly focused on his medical conditions and the medications used to treat them and twice-a-year visits to my childhood home for a few hours were the extent of our relationship ever since my mother suddenly passed away over a decade ago. Hermit-like and fiercely independent despite having significant health issues, he was insistent that he would not live with either my sister or me. Yet, no matter how resolute and disciplined one is, the ... Author, Article, and Disclosure InformationAffiliations: Dublin, OhioCorresponding Author: Joseph M. Geskey, DO, MBA, MS-PopH, 9314 Tartan Ridge Boulevard, Dublin, OH 43017; e-mail, [email protected]net. PreviousarticleNextarticle Advertisement Audio Reading - “When Only Words Are Left” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads “When Only Words Are Left” by Joseph M. Geskey, DO, MBA, MS-PopH 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 December 2021Volume 174, Issue 12Page: 1764-1765 ePublished: 21 December 2021 Issue Published: December 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Correction to: Two Pituitary Neuroendocrine Tumors (PitNETs) with Very High Proliferation and TP53 Mutation – High‑Grade PitNET or PitNEC?
Authors: Wolfgang Saeger, Christian Mawrin, Matthias Meinhardt, Annika K. Wefers, Frank Jacobsen
Journal: Endocrine Pathology (2021)
Advanced therapeutic strategy for hereditary neuromuscular diseases
Authors: Wuh-Liang Hwu, Shin-ichi Muramatsu, Yin-Hsiu Chien, Barry J. Byrne
Journal: Molecular Therapy (2021)

Two manuscripts published recently in The Lancet Child and Adolescent Health, both address the efficacy of an advanced therapeutic strategy for hereditary neuromuscular diseases. Weiß et al. present real-world evidence of gene replacement therapy in spinal muscular atrophy (SMA).1 SMA is a hereditary lower motor neuron disease sharing a global incidence of around 1 in 10,000 live births.2 SMA was first described clinically in the 1890s but the first disease-modifying treatment, the antisense agent nusinersen (Spinraza), was only approved by the FDA in 2016.
National Institutes of Health Funding Priorities
Authors: Rohan Hazra, Diana W. Bianchi
Journal: JAMA Pediatrics (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Covid-19: Whatever happened to the Novavax vaccine?
Authors: Serena Tinari, Catherine Riva
Journal: BMJ (2021)

Novavax had a vaccine with big promise. Its more traditional technology and easy storage attracted big global investment but, as year two of the pandemic draws to a close, the company struggles with regulators, disappoints hopeful governments, and lags far behind its competitors. Is there still hope, ask <b>Serena Tinari</b> and <b>Catherine Riva</b>
Black Men Receiving Radiotherapy for Localized Prostate Cancer Have Improved Outcomes—Clinical Trial Access or Racial Advantage?
Authors: Bogdana Schmidt, Neeraj Agarwal
Journal: JAMA Network Open (2021)

Ting Martin Ma, MD, PhD; Tahmineh Romero, MS; Nicholas G. Nickols, MD, PhD; Matthew B. Rettig, MD; Isla P. Garraway, MD, PhD; Mack Roach 3rd, MD; Jeff M. Michalski, MD, MBA; Thomas M. Pisansky, MD; W. Robert Lee, MD; Christopher U. Jones, MD; Seth A. Rosenthal, MD; Chenyang Wang, MD, PhD; Holly Hartman, MS; Paul L. Nguyen, MD; Felix Y. Feng, MD; Paul C. Boutros, PhD; Christopher Saigal, MD; Karim Chamie, MD; William C. Jackson, MD; Todd M. Morgan, MD; Rohit Mehra, MD; Simpa S. Salami, MD; Randy Vince, MD; Edward M. Schaeffer, MD; Brandon A. Mahal, MD; Robert T. Dess, MD; Michael L. Steinberg, MD; David Elashoff, PhD; Howard M. Sandler, MD, MS; Daniel E. Spratt, MD; Amar U. Kishan, MD
Subdural neural interfaces for long-term electrical recording, optical microscopy and magnetic resonance imaging
Authors: Xiaomeng Wang, Mengqi Wang, Hao Sheng, Liang Zhu, Junming Zhu, Hequn Zhang, Yin Liu, Li Zhan, Xi Wang, Jiaozhen Zhang, Xiaotong Wu, Zhigang Suo, Wang Xi, Hao Wang
Journal: Biomaterials (2021)

Though commonly used, metal electrodes are incompatible with brain tissues, often leading to injury and failure to achieve long-term implantation. Here we report a subdural neural interface of hydrogel functioning as an ionic conductor, and elastomer as a dielectric. We demonstrate that it incurs a far less glial reaction and less cerebrovascular destruction than a metal electrode. Using a cat model, the hydrogel electrode was able to record electrical signals comparably in quality to a metal electrode. The hydrogel-elastomer neural interface also readily facilitated multimodal functions. Both the hydrogel and elastomer are transparent, enabling in vivo optical microscopy. For imaging, cerebral vessels and calcium signals were imaged using two-photon microscopy. The new electrode is compatible with magnetic resonance imaging and does not cause artifact images. Such a new multimodal neural interface could represent immediate opportunity for use in broad areas of application in neuroscience research and clinical neurology.
Trial of Spesolimab for Generalized Pustular Psoriasis
Authors: Hervé Bachelez, Siew-Eng Choon, Slaheddine Marrakchi, A. David Burden, Tsen-Fang Tsai, Akimichi Morita, Alexander A. Navarini, Min Zheng, Jinhua Xu, Hamida Turki, Milan J. Anadkat, Sushmita Rajeswari, Hairui Hua, Sebastian D. Vulcu, David Hall, Kay Tetzlaff, Christian Thoma, Mark G. Lebwohl
Journal: New England Journal of Medicine (2021)

Generalized pustular psoriasis (GPP) is a rare, life-threatening, inflammatory skin disease characterized by widespread eruption of sterile pustules. Interleukin-36 signaling is involved in the pathogenesis of this disorder. Spesolimab, a humanized anti–interleukin-36 receptor monoclonal antibody, is being studied for the treatment of GPP flares.