tbuckley/cabot-search huggingface dataset:
Staying Apart During a Pandemic
Authors: Nathaniel P. Morris
Journal: JAMA Internal Medicine (2020)

Staying Apart During a PandemicThe walk is clearly ending, and we can all sense it.We stand far apart and chat casually for a few more minutes, 2 couples savoring the moment together outdoors.But we know that we should probably wrap up, head our separate ways, and shelter in place again.People wearing masks walk past us.This is the first time we have seen our friends in person in weeks, and we are not sure when we will see each other again.That is when I feel it.It is hard to describe.A pull.A draw toward my friends.There is a charge of energy in the air.But we know we cannot embrace, and we do not.Separated by just 6 feet of air, we talk about how great it was to walk together and how much we miss each other.We make tenuous plans to spend time together again in the coming weeks.The good-bye feels incomplete, yet we walk away from each other.Is there a word for the absence of an embrace during a pandemic?Does the phrase social distancing capture what it means to be kept apart?Too often, the English language struggles to articulate the experience of our daily lives, and there are plenty of instances where other languages can achieve what English cannot.In French, the phrase la douleur exquise translates as the exquisite pain, which has been used to signify not only sharp, localized pain in medicine but also feelings of unrequited love in romantic contexts.In German, the word weltschmerz translates directly to world pain, representing something akin to the sorrows that we feel when we realize the imperfections of the world around us.Language can often help us recognize subtle aspects of our shared experiences; however, the realities of a pandemic can still leave us at a loss for words.At the time of her college graduation in 2012, author Marina Keegan wrote that "We don't have a word for the opposite of loneliness, but if we did, I could say that's what I want in life." 1 Keegan died in a car crash just days after her graduation, and her moving essay drew international attention.Eight years later, her wish seems to be what so many of us want in our lives.With a pandemic upon us, social distancing has become a guiding principle, as we all do our best to stay apart, to remain in good health, to prevent the spread of infection.Social distancing has brought concerns about the possibility of an epidemic of social isolation, which could bring its own set of health challenges.Widespread social isolation could exacerbate the toll of mental illness and potentially increase risks of suicide. 2,3Lack of social interaction could place vulnerable populations, such as elderly individuals or people living with disabilities, at additional risk for adverse health outcomes. 4,5 It is possible to maintain social connection and to keep our distance from one another during a pandemic, for example by connecting through video conferences, phone calls, emails, or text messages.
Effectiveness of secukinumab versus an alternative TNF inhibitor in patients with axial spondyloarthritis previously exposed to TNF inhibitors in the Swiss Clinical Quality Management cohort
Authors: Raphael Micheroli, Christoph Tellenbach, Almut Scherer, Kristina Bürki, Karin Niederman, Michael J Nissen, Pascal Zufferey, Pascale Exer, Burkhard Möller, Diego Kyburz, Adrian Ciurea
Journal: Annals of the Rheumatic Diseases (2020)

Objective To compare effectiveness of treatment with secukinumab (SEC) with that of alternative tumour necrosis factor inhibitors (TNFis) in patients with axial spondyloarthritis (axSpA) after withdrawal from one or more TNFis. Methods Patients diagnosed as having axSpA in the Swiss Clinical Quality Management cohort were included if they had initiated SEC (n=106) or an alternative TNFi (n=284) after experiencing TNFi failure. Drug retention was investigated with matching weights propensity score (PS) analyses and multiple adjusted Cox proportional hazards models. Matching weights PS-based analyses and multiple-adjusted logistic regression analyses were used to assess the proportion of patients reaching 50% reduction in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50) at 1 year. Results SEC was more often used as third-line or later-line biological drug (76% vs 40% for TNFi). Patients starting SEC had higher BASDAI, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Metrology Index and C reactive protein levels. A comparable risk of drug discontinuation was found for SEC versus TNFi (HR 1.14, 95% CI 0.78 to 1.68 in the PS-based analysis and HR 1.16, 95% CI 0.79 to 1.71 in the multiple-adjusted analysis). No significant difference in BASDAI50 responses at 1 year was demonstrated between the two modes of biological drug action, with CI of estimates being, however, wide (OR for SEC vs TNFi 0.76, 95% CI 0.26 to 2.18 and 0.78, 95% CI 0.24 to 2.48 in the PS-based and the covariate-adjusted model, respectively). Conclusion Our data suggest a comparable effectiveness of SEC versus an alternative TNFi after prior TNFi exposure.
Reply to: Oncolytic Viral Therapy for Malignant Pleural Mesothelioma
Authors: Didier Jean, Tiphaine Delaunay, Clément Meiller, Nicolas Boisgerault, Marion Grard, Stefano Caruso, Christophe Blanquart, Emanuela Felley-Bosco, Jaafar Bennouna, Frédéric Tangy, Marc Grégoire, Jean-François Fonteneau
Journal: Journal of Thoracic Oncology (2020)
SLIR: Synthesis, localization, inpainting, and registration for image-guided thermal ablation of liver tumors
Authors: Dongming Wei, Sahar Ahmad, Jiayu Huo, Pu Huang, Pew-Thian Yap, Zhong Xue, Jianqi Sun, Wentao Li, Dinggang Shen, Qian Wang
Journal: Medical Image Analysis (2020)
Serial Measurement of Cell-Cycle Arrest Biomarkers [TIMP-2] · [IGFBP7] and Risk for Progression to Death, Dialysis, or Severe Acute Kidney Injury in Patients with Septic Shock
Authors: Marco Fiorentino, Zhongying Xu, Ali Smith, Kai Singbartl, Paul M. Palevsky, Lakhmir S. Chawla, David T. Huang, Donald M. Yealy, Derek C. Angus, John A. Kellum, Derek C. Angus, Lakhmir S. Chawla, David T. Huang, Christopher Keener, John A. Kellum, Nicole Lucko, Paul M. Palevsky, Francis Pike, Kai Singbartl, Ali Smith, Donald M. Yealy, Sachin Yende, Raghavan Murugan, Lan Kong, Sachin Yende, Xiaoyan Wen
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Urinary TIMP-2 (tissue inhibitor of metalloproteinases-2) and IGFBP7 (insulin-like growth factor–binding protein 7) can predict acute kidney injury (AKI) in patients with sepsis.Objectives: To address critical questions about whether biomarkers can inform the response to treatment and whether they might be used to guide therapy, as most sepsis patients present with AKI.Methods: We measured [TIMP-2] · [IGFBP7] before and after a 6-hour resuscitation in 688 patients with septic shock enrolled in the ProCESS (Protocol-based Care for Early Septic Shock) trial. Our primary endpoint was stage 3 AKI, renal replacement therapy, or death within 7 days.Measurements and Main Results: The endpoint was reached in 113 patients (16.4%). In patients with negative [TIMP-2] · [IGFBP7] at baseline, those who became positive (>0.3 U) after resuscitation had three-times higher risk compared with those who remained negative (21.8% vs. 8.5%; P = 0.01; odds ratio [OR], 3.0; 95% confidence interval [CI], 1.31–6.87). Conversely, compared with patients with a positive biomarker at baseline that were still positive at Hour 6, risk was reduced for patients who became negative (23.8% vs. 9.8%; P = 0.01; OR, 2.15; 95% CI, 1.17–3.95). A positive [TIMP-2] · [IGFBP7] after resuscitation was associated with worse outcomes in both patients with and without AKI at that time point. The clinical response to resuscitation, as judged by the Acute Physiology and Chronic Health Evaluation II score, was weakly predictive of the endpoint (area under the curve, 0.68; 95% CI, 0.62–0.73) and improved with addition of [TIMP-2] · [IGFBP7] (0.72; 95% CI, 0.66–0.77; P = 0.03). Different resuscitation protocols did not alter biomarker trajectories, nor did they alter outcomes in biomarker-positive or biomarker-negative patients. However, biomarker trajectories were associated with outcomes.Conclusions: Changes in urinary [TIMP-2] · [IGFBP7] after initial fluid resuscitation identify patients with sepsis who have differing risk for progression of AKI.Clinical trial registered with www.clinicaltrials.gov (NCT 00510835).
Barry Ian Hoffbrand: national leader in postgraduate medical education
Authors: Philip Graham
Journal: BMJ (2020)

Barry Ian Hoffbrand was a national leader in postgraduate medical education. From 1980 to 1994 he was editor of the Postgraduate Medical Journal . In this position he created a viable and successful clinical educational journal to rival the best. In the view of his successors, it was “a reflection of his industry, dedication to quality and accuracy, and his wise editorial judgment that the journal came to occupy its successful position in the medical publishing world.” 

Barry’s experience in postgraduate education was developed locally in his position as consultant physician to the Whittington Hospital, in north London. This hospital had a long tradition of providing excellent training in postgraduate medicine. Eventually an academic centre for postgraduate medicine was established there, and Barry was its director from 1975 to 1981. In this capacity he helped countless junior doctors succeed in passing challenging postgraduate medical examinations.

After his appointment as consultant to the Whittington in 1970, Barry rapidly built up a reputation as a brilliant diagnostician and wise medical opinion. Over his nearly 30 year tenure in this post, he came to be regarded as the physician other doctors would consult about their own medical problems. Especially in the days before imaging made diagnosis of conditions such as endocarditis much easier, he was able to work out what was wrong with patients when other …
Genetic reduction of cilium length by targeting intraflagellar transport 88 protein impedes kidney and liver cyst formation in mouse models of autosomal polycystic kidney disease
Authors: Lina Shao, Wassim El-Jouni, Fanwu Kong, Janani Ramesh, Radhe Shantha Kumar, Xiaogang Shen, Jingjing Ren, Shruti Devendra, Arianna Dorschel, Maoqing Wu, Ivan Barrera, Azadeh Tabari, Kang Hu, Nadeem Haque, Ilyas Yambayev, Shiqi Li, Amresh Kumar, Tapas Ranjan Behera, Gregory McDonough, Masahito Furuichi, Michael Xifaras, Tzongshi Lu, Rami Mohammad Alhayaza, Koji Miyabayashi, Qiuling Fan, Amrendra K. Ajay, Jing Zhou
Journal: Kidney International (2020)
Evaluation of Intraoperative Near-Infrared Fluorescence Visualization of the Lung Tumor Margin With Indocyanine Green Inhalation
Authors: Yu Hua Quan, Chan Hee Oh, Daeho Jung, Ji-Young Lim, Byeong Hyeon Choi, Jiyun Rho, Yeonho Choi, Kook Nam Han, Beop-Min Kim, Chungyeul Kim, Ji-Ho Park, Hyun Koo Kim
Journal: JAMA Surgery (2020)

Identification of the tumor margin during surgery is important for precise minimal resection of lung tumors. Intravenous injection of indocyanine green (ICG) has several limitations when used for intraoperative visualization of lung cancer.To describe a technique for intraoperative visualization of lung tumor margin using ICG inhalation and evaluate the clinical applicability of the technique in mouse and rabbit lung tumor models as well as lung specimens of patients with lung tumors.In lung tumor models of both mice and rabbits, the distribution of inhaled ICG in the lung tumor margin was investigated in vivo and ex vivo using a near-infrared imaging system. Lung tumor margin detection via inhalation of ICG was evaluated by comparing the results obtained with those of the intravenous injection method (n = 32, each time point for 4 mice). Based on preclinical data, use of ICG inhalation to help detect the tumor margin in patients with lung cancer was also evaluated (n = 6). This diagnostic study was conducted from May 31, 2017, to March 30, 2019.The use of tumor margin detection by inhaled ICG was evaluated by comparing the inhaled formulation with intravenous administration of ICG.From 10 minutes after inhalation of ICG to 24 hours, the distribution of ICG in the lungs was significantly higher than that in other organs (signal to noise ratio in the lungs: 39 486.4; interquartile range [IQR], 36 983.74-43 592.5). Ex vivo and histologic analysis showed that, in both lung tumor models, inhaled ICG was observed throughout the healthy lung tissue but was rarely found in tumor tissue. The difference in the fluorescent signal between healthy and tumor lung tissues was associated with the mechanical airway obstruction caused by the tumor and with alveolar macrophage uptake of the inhaled ICG in healthy tissues. Inhalation at a 20-fold lower dose of ICG had a 2-fold higher efficiency for tumor margin detection than did the intravenous injection (2.9; IQR, 2.7-3.2; P < .001).The results of this study suggest that lung-specific inhalation delivery of ICG is feasible and may be useful for the intraoperative visualization of lung tumor margin in clinical practice.
Cbl and Cbl-b control the germinal center reaction by facilitating naive B cell antigen processing
Authors: Xin Li, Liying Gong, Alexandre P. Meli, Danielle Karo-Atar, Weili Sun, Yongrui Zou, Irah L. King, Hua Gu
Journal: The Journal of Experimental Medicine (2020)

Antigen uptake and presentation by naive and germinal center (GC) B cells are different, with the former expressing even low-affinity BCRs efficiently capture and present sufficient antigen to T cells, whereas the latter do so more efficiently after acquiring high-affinity BCRs. We show here that antigen uptake and processing by naive but not GC B cells depend on Cbl and Cbl-b (Cbls), which consequently control naive B and cognate T follicular helper (Tfh) cell interaction and initiation of the GC reaction. Cbls mediate CD79A and CD79B ubiquitination, which is required for BCR-mediated antigen endocytosis and postendocytic sorting to lysosomes, respectively. Blockade of CD79A or CD79B ubiquitination or Cbls ligase activity is sufficient to impede BCR-mediated antigen processing and GC development. Thus, Cbls act at the entry checkpoint of the GC reaction by promoting naive B cell antigen presentation. This regulation may facilitate recruitment of naive B cells with a low-affinity BCR into GCs to initiate the process of affinity maturation.
Increasing Fatty Acid Oxidation Prevents High-Fat Diet–Induced Cardiomyopathy Through Regulating Parkin-Mediated Mitophagy
Authors: Dan Shao, Stephen C. Kolwicz, Pei Wang, Nathan D. Roe, Outi Villet, Kiyoto Nishi, Yun-Wei A. Hsu, Galina V. Flint, Arianne Caudal, Wang Wang, Michael Regnier, Rong Tian
Journal: Circulation (2020)

Increased fatty acid oxidation (FAO) has long been considered a culprit in the development of obesity/diabetes mellitus-induced cardiomyopathy. However, enhancing cardiac FAO by removing the inhibitory mechanism of long-chain fatty acid transport into mitochondria via deletion of acetyl coenzyme A carboxylase 2 (ACC2) does not cause cardiomyopathy in nonobese mice, suggesting that high FAO is distinct from cardiac lipotoxicity. We hypothesize that cardiac pathology-associated obesity is attributable to the imbalance of fatty acid supply and oxidation. Thus, we here seek to determine whether further increasing FAO by inducing ACC2 deletion prevents obesity-induced cardiomyopathy, and if so, to elucidate the underlying mechanisms.We induced high FAO in adult mouse hearts by cardiac-specific deletion of ACC2 using a tamoxifen-inducible model (ACC2 iKO). Control and ACC2 iKO mice were subjected to high-fat diet (HFD) feeding for 24 weeks to induce obesity. Cardiac function, mitochondria function, and mitophagy activity were examined.Despite both control and ACC2 iKO mice exhibiting a similar obese phenotype, increasing FAO oxidation by deletion of ACC2 prevented HFD-induced cardiac dysfunction, pathological remodeling, and mitochondria dysfunction, as well. Similarly, increasing FAO by knockdown of ACC2 prevented palmitate-induced mitochondria dysfunction and cardiomyocyte death in vitro. Furthermore, HFD suppressed mitophagy activity and caused damaged mitochondria to accumulate in the heart, which was attenuated, in part, in the ACC2 iKO heart. Mechanistically, ACC2 iKO prevented HFD-induced downregulation of parkin. During stimulation for mitophagy, mitochondria-localized parkin was severely reduced in control HFD-fed mouse heart, which was restored, in part, in ACC2 iKO HFD-fed mice.These data show that increasing cardiac FAO alone does not cause cardiac dysfunction, but protects against cardiomyopathy in chronically obese mice. The beneficial effect of enhancing cardiac FAO in HFD-induced obesity is mediated, in part, by the maintenance of mitochondria function through regulating parkin-mediated mitophagy. Our findings also suggest that targeting the parkin-dependent mitophagy pathway could be an effective strategy against the development of obesity-induced cardiomyopathy.
Using routine health data for research: the devil is in the detail
Authors: Hannah Whittaker, Jennifer K Quint
Journal: Thorax (2020)

Electronic healthcare records (EHRs) are increasingly being used for population-based studies globally. Despite their strengths, hidden pitfalls exist and researchers must take extra care to ensure high-quality data to minimise measurement error and biasses. This article discusses the recent work by Kerkhof et al , in relation to disease misdiagnosis and misclassification, the importance of linked data sources and the usability of test variables; all of which are extremely important issues that researchers must be aware of when using EHRs. The devil is in the detail.

EHR databases systematically and routinely collect and store healthcare data electronically and can include data on routine processes in primary and secondary care (disease codes, prescriptions, procedures and tests). The information collected ranges from medical insurance claims, to mortality data, to specific disease registries, with each database coding and storing information differently. The original purpose of EHRs was simply to store medical information digitally. But EHRs are increasingly being used for research and population-based studies globally, offering large sample sizes, a wide breadth of study variables and the inclusion of more generalisable populations.

However, nothing is ever perfect and routinely collected EHR data can have issues; the devil is in the detail. Unlike studies which include purposeful prospective data collection, the original purpose of data collection for EHRs is not research; a controversial argument in data science.1 So, while EHRs allow researchers to study real-world populations seen in every day clinical practice, extra care must be taken to ensure the quality of the …
Academic criteria for promotion and tenure in biomedical sciences faculties: cross sectional analysis of international sample of universities
Authors: Danielle B Rice, Hana Raffoul, John P A Ioannidis, David Moher
Journal: BMJ (2020)

To determine the presence of a set of pre-specified traditional and non-traditional criteria used to assess scientists for promotion and tenure in faculties of biomedical sciences among universities worldwide.Cross sectional study.International sample of universities.170 randomly selected universities from the Leiden ranking of world universities list.Presence of five traditional (for example, number of publications) and seven non-traditional (for example, data sharing) criteria in guidelines for assessing assistant professors, associate professors, and professors and the granting of tenure in institutions with biomedical faculties.A total of 146 institutions had faculties of biomedical sciences, and 92 had eligible guidelines available for review. Traditional criteria of peer reviewed publications, authorship order, journal impact factor, grant funding, and national or international reputation were mentioned in 95% (n=87), 37% (34), 28% (26), 67% (62), and 48% (44) of the guidelines, respectively. Conversely, among non-traditional criteria, only citations (any mention in 26%; n=24) and accommodations for employment leave (37%; 34) were relatively commonly mentioned. Mention of alternative metrics for sharing research (3%; n=3) and data sharing (1%; 1) was rare, and three criteria (publishing in open access mediums, registering research, and adhering to reporting guidelines) were not found in any guidelines reviewed. Among guidelines for assessing promotion to full professor, traditional criteria were more commonly reported than non-traditional criteria (traditional criteria 54.2%, non-traditional items 9.5%; mean difference 44.8%, 95% confidence interval 39.6% to 50.0%; P=0.001). Notable differences were observed across continents in whether guidelines were accessible (Australia 100% (6/6), North America 97% (28/29), Europe 50% (27/54), Asia 58% (29/50), South America 17% (1/6)), with more subtle differences in the use of specific criteria.This study shows that the evaluation of scientists emphasises traditional criteria as opposed to non-traditional criteria. This may reinforce research practices that are known to be problematic while insufficiently supporting the conduct of better quality research and open science. Institutions should consider incentivising non-traditional criteria.Open Science Framework (https://osf.io/26ucp/?view_only=b80d2bc7416543639f577c1b8f756e44).
Progressive fibrosing interstitial lung disease: we know it behaves badly, but what does that mean?
Authors: Amornpun Wongkarnjana, Christopher J. Ryerson
Journal: European Respiratory Journal (2020)

<b>The criteria used to define progressive fibrosing interstitial lung disease identify a rapidly progressive phenotype that behaves like idiopathic pulmonary fibrosis, regardless of the underlying diagnosis</b>https://bit.ly/3bW5DIV
Cardiac Data From the Women’s National Basketball Association—Caring for Women Requires Studying Women
Authors: Aaron L. Baggish
Journal: JAMA Cardiology (2020)

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