tbuckley/cabot-search huggingface dataset:
Decreasing Incidence of Estrogen Receptor–Negative Breast Cancer in the United States: Trends by Race and Region
Authors: Brittny C Davis Lynn, Pavel Chernyavskiy, Gretchen L Gierach, Philip S Rosenberg
Journal: JNCI Journal of the National Cancer Institute (2021)

Incidence of estrogen receptor (ER)-negative breast cancer, an aggressive subtype, is highest in US African American women and in Southern residents but has decreased overall since 1992. We assessed whether ER-negative breast cancer is decreasing in all age groups and cancer registries among non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic White (HW) women.We analyzed 17 Surveillance, Epidemiology, and End-Results (SEER) Program registries (12 for 1992-2016; 5 for 2000-2016) to assess NHW, NHB, and HW trends by ER status and age group (30-39 years, 40-49 years, 50-69 years, 70-84 years). We used hierarchical age-period-cohort models that account for sparse data, which improve estimates to quantify between-registry heterogeneity in mean incidence rates and age-adjusted trends vs SEER overall.Overall, ER-negative incidence was highest in NHB, then NHW and HW women, and decreased from 1992-2016 in each age group and racial or ethnic group. The greatest decrease was for HW women aged 40-49 years, with an annual percent change of -3.5%/y (95% credible interval = -4.4%, -2.7%) averaged over registries. The trend heterogeneity was statistically significant in every race or ethnic and age group. Furthermore, the incidence relative risks by race or ethnicity compared with the race-specific SEER average were also statistically significantly heterogeneous across the majority of registries and age groups (62 of 68 strata). The greatest heterogeneity was seen in HW women, followed by NHB women, and the least in NHW women.Decreasing ER-negative breast cancer incidence differs meaningfully by US region and age among NHB and HW women. Analytical studies including minority women from higher and lower incidence areas may provide insights into breast cancer racial disparities.
Damian Vincent McGivern
Authors: John Puntis
Journal: BMJ (2021)

Damian Vincent McGivern came from a Liverpool Irish family and remained deeply attached to his roots. Educated at the Christian Brothers School in Crosby, he excelled both academically and at sport. Moving on to the University of Southampton in 1972, he was in the second intake of the new medical school and with his good humour, intelligence, and charm made many friends. An elective period at the end of the third year gave him the chance to spend time on clinical attachment in Dublin, an …
New Variant With a Previously Unrecognized Mechanism of Pathogenicity in Hypertrophic Cardiomyopathy
Authors: Yasmine Aguib, Mona Allouba, Roddy Walsh, Ayman M. Ibrahim, Sarah Halawa, Alaa Afify, Mohammed Hosny, Pantazis I. Theotokis, Aya Galal, Sara Elshorbagy, Mohamed Roshdy, Heba S. Kassem, Amany Ellithy, Rachel Buchan, Nicola Whiffin, Shehab Anwer, Stuart A. Cook, Ahmed Moustafa, Ahmed ElGuindy, James S. Ware, Paul J.R. Barton, Magdi Yacoub
Journal: Circulation (2021)
Analysis of mutation status and homologous recombination deficiency in tumors of patients with germline BRCA1 or BRCA2 mutations and metastatic breast cancer: OlympiAD
Authors: D. Hodgson, Z. Lai, S. Dearden, J.C. Barrett, E.A. Harrington, K. Timms, J. Lanchbury, W. Wu, A. Allen, E. Senkus, S.M. Domchek, M. Robson
Journal: Annals of Oncology (2021)
제5차 대한간학회 춘계학술대회 초록집 : 간세포암에 대한 경피적 에탄올주입술 후 재발 양상과 그 예견 인자
Authors: 김강모 ( Kim Gang Mo ), 윤정환 ( Yun Jeong Hwan ), 우광훈 ( U Gwang Hun ), 이효석 ( Lee Hyo Seog ), 김정룡 ( Kim Jeong Lyong )
Journal: Clinical and Molecular Hepatology (1999)
Fab and Fc contribute to maximal protection against SARS-CoV-2 following NVX-CoV2373 subunit vaccine with Matrix-M vaccination
Authors: Matthew J. Gorman, Nita Patel, Mimi Guebre-Xabier, Alex L. Zhu, Caroline Atyeo, Krista M. Pullen, Carolin Loos, Yenny Goez-Gazi, Ricardo Carrion, Jing-Hui Tian, Dansu Yuan, Kathryn A. Bowman, Bin Zhou, Sonia Maciejewski, Marisa E. McGrath, James Logue, Matthew B. Frieman, David Montefiori, Colin Mann, Sharon Schendel, Fatima Amanat, Florian Krammer, Erica Ollmann Saphire, Douglas A. Lauffenburger, Ann M. Greene, Alyse D. Portnoff, Michael J. Massare, Larry Ellingsworth, Gregory Glenn, Gale Smith, Galit Alter
Journal: Cell Reports Medicine (2021)
Correction: Siglec-15 as an Emerging Target for Next-generation Cancer Immunotherapy
Authors: Jingwei Sun, Qiao Lu, Miguel F. Sanmamed, Jun Wang
Journal: Clinical Cancer Research (2021)

In the original version of [this article][1] ([1][2]), author Miguel F. Sanmamed's name was spelled incorrectly. The error has been corrected in the latest online HTML and PDF versions of the article. The authors regret this error. 1. 1.[↵][3]1. Sun J, 2. Lu Q, 3. Sanmamed MF,
Assessing procedural pain in infants: a feasibility study evaluating a point-of-care mobile solution based on automated facial analysis
Authors: Kreshnik Hoti, Paola Teresa Chivers, Jeffery David Hughes
Journal: The Lancet Digital Health (2021)

The management of procedural pain in infants is suboptimal, in part, compounded by the scarcity of a simple, accurate, and reliable method of assessing such pain. In this study, we aimed to evaluate the psychometric properties of the PainChek Infant, a point-of-care mobile application that uses automated facial evaluation and analysis in the assessment of procedural pain in infants.Video recordings of 40 infants were randomly chosen from a purposely assembled digital library of 410 children undergoing immunisation as part of their standard care in Prishtina, Kosovo, between April 4, 2017, and July 11, 2018. For each infant recording, four 10 s video segments were extracted, corresponding to baseline, vaccine preparation, during vaccination, and recovery. Four trained assessors did pain assessments on the video segments of 30 infants, using PainChek Infant standard, PainChek Infant adaptive, the Neonatal Facial Coding System-Revised (NFCS-R) single, the NFCS-R multiple, and the Observer administered Visual Analogue Scale (ObsVAS), on two separate occasions. PainChek Infant's performance was compared to NFCS-R and ObsVAS using correlation in changes in pain scores, intra-rater and inter-rater reliability, and internal consistency.4303 pain assessments were completed in two separate testing sessions, on Aug 31, and Oct 19, 2020. The study involved videos of 40 infants aged 2·2-6·9 months (median age 3·4 months [IQR 2·3-4·5]). All pain assessment tools showed significant changes in the recorded pain scores across the four video segments (p≤0·0006). All tools were found to be responsive to procedure-induced pain, with the degree of change in pain scores not influenced by pre-vaccination pain levels. PainChek Infant pain scores showed good correlation with NFCS-R and ObsVAS scores (r=0·82-0·88; p<0·0001). PainChek Infant also showed good to excellent inter-rater reliability (ICC=0·81-0·97, p<0·001) and high levels of internal consistency (α=0·82-0·97).PainChek Infant's use of automated facial expression analysis could offer a valid and reliable means of assessing and monitoring procedural pain in infants. Its clinical utility in clinical practice requires further research.PainChek.
Discontinuation of nucleot(s)ide analogue therapy in HBeAg-negative chronic hepatitis B: a meta-analysis
Authors: Samuel Anthony Lachlan Hall, Sara Vogrin, Olivia Wawryk, Gareth S Burns, Kumar Visvanathan, Vijaya Sundararajan, Alexander Thompson
Journal: Gut (2021)

Background and aims Sustained virological suppression and hepatitis B surface antigen (HBsAg) loss have been described after nucleot(s)ide analogue (NA) discontinuation for patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). We performed a meta-analysis of the clinical outcomes after NA discontinuation for HBeAg-negative CHB. Methods Studies involving NA cessation in HBeAg-negative CHB individuals with a median follow-up of ≥12 months were included. Participants were HBeAg-negative at the time of NA initiation. Random effects meta-analyses were performed for the following clinical outcomes: (1) virological relapse (VR) at 6 and 12 months; (2) clinical relapse (CR) at 6 and 12 months and (3) HBsAg loss. Effect of other variables was estimated using subgroup analysis and meta-regression. Studies including patients stopping entecavir (ETV) and/or tenofovir disoproxil fumarate (TDF) were considered separately to studies including patients stopping older generation NA. Results N=37 studies met inclusion criteria. Cumulative incidence of VR and CR after stopping ETV/TDF was 44% and 17% at 6 months and 63% and 35% at 12 months. Similar relapse rates were observed after stopping older NAs. Among patients stopping ETV/TDF, TDF cessation was associated with increased CR rates at 6 months versus ETV. There was an association between follow-up ≥4 years and HBsAg loss rates when stopping older NAs. Hepatic decompensation and hepatocellular carcinoma were rare but occurred more frequently in studies including cirrhotic individuals. Conclusion VR is common after NA discontinuation, however, CR was only seen in one-third of patients at 12 months. Stopping NA therapy can be followed by HBsAg clearance, and rates are higher with longer follow-up.
Comprehensive characterization of viral integrations and genomic aberrations in HBV‐infected intrahepatic cholangiocarcinomas
Authors: Jihyun An, Deokhoon Kim, Bora Oh, Yoo‐Jin Oh, Jihyun Song, Naomi Park, Ha Il Kim, Hyo Jeong Kang, Ji‐Hye Oh, Wonkyung Kim, Eunjung Lee, Chang Ohk Sung, Gi‐Won Song, Dae‐Ghon Kim, Eunsil Yu, Eric Letouzé, Jessica Zucman‐Rossi, Han Chu Lee, Ju Hyun Shim
Journal: Hepatology (2021)

Abstract Background and Aims Despite the epidemiological association between intrahepatic cholangiocarcinoma (iCCA) and HBV infection, little is known about the relevant oncogenic effects. We sought to identify the landscape and mechanism of HBV integration, along with the genomic architecture of HBV‐infected iCCA (HBV‐iCCA) tumors. Approach and Results We profiled a cohort of 108 HBV‐iCCAs using whole‐genome sequencing, deep sequencing, and RNA sequencing, together with preconstructed data sets of HBV‐infected HCC (HBV‐HCC; n = 167) and combined hepatocellular cholangiocarcinoma (HBV‐cHCC/CCA; n = 59), and conventional ( n = 154) and fluke‐related iCCAs ( n = 16). Platforms based on primary iCCA cell lines to evaluate the functional effects of chimeric transcripts were also used. We found that HBV had inserted at multiple sites in the iCCA genomes in 45 (41.7%) of the tumors. Recurrent viral integration breakpoints were found at nine different sites. The most common insertional hotspot (7 tumors) was in the TERT (telomerase reverse transcriptase) promoter, where insertions and mutations (11 tumors) were mutually exclusive, and were accompanied by promoter hyperactivity. Recurrent HBV integration events (5 tumors) were also detected in FAT2 (FAT atypical cadherin 2), and were associated with enrichment of epithelial–mesenchymal transition–related genes. A distinctive intergenic insertion (chr9p21.3), between DMRTA1 (DMRT like family A1) and LINC01239 (long intergenic non‐protein coding RNA 1239), had oncogenic effects through activation of the mammalian target of rapamycin (mTOR)/4EBP/S6K pathway. Regarding the mutational profiles of primary liver cancers, the overall landscape of HBV‐iCCA was closer to that of nonviral conventional iCCA, than to HBV‐HCC and HBV‐cHCC/CCA. Conclusions Our findings provide insight into the behavior of iCCAs driven by various pathogenic mechanisms involving HBV integration events and associated genomic aberrations. This knowledge should be of use in managing HBV carriers.
Considering climate and conflict conditions together to improve interventions that prevent child acute malnutrition
Authors: Molly E Brown, Kathryn Grace, Trey Billing, David Backer
Journal: The Lancet Planetary Health (2021)

Despite early warning signs about threats to food security, humanitarian interventions often lag behind these warning signs. Climate and conflict conditions are among the most important factors preceding food system failures and malnutrition crises around the world. Research shows how conflict and climate conditions can upend functional food and economic systems, but this research does not address the severe health impacts of these conditions on infants and young children. Translating quantitative research findings into humanitarian interventions requires geographical detail, resulting in location-specific alerts of risks of food insecurity. We describe how the use of readily available, spatially referenced quantitative data can support targeted interventions for nutrition resiliency. Effective humanitarian programmes for targeted nutrition interventions require real-time datasets on food security drivers and models that can provide actionable guidance to mitigate negative impacts of conflict and climate conditions on the people most susceptible to food insecurity. Although treatment of acute malnutrition is important, treating existing malnutrition is not enough. Instead, action to prevent acute malnutrition should be taken to minimise suffering and to maximise wellbeing, particularly in contexts prone to worsening climate and conflict conditions.
Estimating Longitudinal Risks and Benefits From Cardiovascular Preventive Therapies Among Medicare Patients
Authors: Donald M. Lloyd-Jones, Mark D. Huffman, Kunal N. Karmali, Darshak M. Sanghavi, Janet S. Wright, Colleen Pelser, Martha Gulati, Frederick A. Masoudi, David C. Goff
Journal: Journal of the American College of Cardiology (2016)
Robin Touquet: emeritus professor of emergency medicine who strove for greater understanding of alcohol misuse across all medical specialties
Authors: Joanna Lyall
Journal: BMJ (2021)

When Robin Touquet was appointed the first consultant in emergency medicine at St Mary’s Hospital in London in July 1986, he was struck by the number of patients collapsing from alcohol misuse and began to lobby support for more resources. But he was rebuffed by a senior colleague who said, “Robin, be a man, it’s just part of your work.” Touquet retorted that he was both a man and ex-Royal Marines, “and I do not like being patronised.”

Shortly afterwards he set out his vision for the new specialty1 and went about developing the department he would lead for 25 years with military determination, once sending the police to find a junior doctor who had failed to appear at the mandatory 8 am meeting. “This is not a specialty for the fainthearted,” he pointed out.

From its early days when the department was known as “the bear pit,” staffed by just five …
Call for emergency action to limit global temperature increases, restore biodiversity and protect health
Authors: Lukoye Atwoli, Abdullah H Baqui, Thomas Benfield, Raffaella Bosurgi, Fiona Godlee, Stephen Hancocks, Richard Horton, Laurie Laybourn-Langton, Carlos Augusto Monteiro, Ian Norman, Kirsten Patrick, Nigel Praities, Marcel GM Olde Rikkert, Eric J Rubin, Peush Sahni, Richard Smith, Nicholas J Talley, Sue Turale, Damián Vázquez
Journal: Thorax (2021)

> Wealthy nations must do much more, much faster.

The United Nations General Assembly in September 2021 will bring countries together at a critical time for marshalling collective action to tackle the global environmental crisis. They will meet again at the biodiversity summit in Kunming, China, and the climate conference (Conference of the Parties (COP)26) in Glasgow, UK. Ahead of these pivotal meetings, we—the editors of health journals worldwide—call for urgent action to keep average global temperature increases below 1.5°C, halt the destruction of nature and protect health.

Health is already being harmed by global temperature increases and the destruction of the natural world, a state of affairs health professionals have been bringing attention to for decades.1 The science is unequivocal; a global increase of 1.5°C above the preindustrial average and the continued loss of biodiversity risk catastrophic harm to health that will be impossible to reverse.2 3 Despite the world’s necessary preoccupation with COVID-19, we cannot wait for the pandemic to pass to rapidly reduce emissions.

Reflecting the severity of the moment, this editorial appears in health journals across the world. We are united in recognising that only fundamental and equitable changes to societies will reverse our current trajectory.

The risks to health of increases above 1.5°C are now well established.2 Indeed, no temperature rise is ‘safe’. In the past 20 years, heat-related mortality among people aged over 65 has increased by more than 50%.4 Higher temperatures have brought increased dehydration and renal function loss, dermatological malignancies, tropical infections, adverse mental health outcomes, pregnancy complications, allergies, and cardiovascular and pulmonary morbidity and mortality.5 6 Harms disproportionately affect the most vulnerable, including children, older populations, ethnic minorities, poorer communities and those with underlying health problems.2 4

Global heating is also contributing to the decline in …
P21: Practising dermatology in the era of COVID‐19: a tertiary centre’s experience of adapting to change
Authors: C Psomadakis, A Connolly, L Nestor, S Walsh, E Craythorne
Journal: British Journal of Dermatology (2021)

the need for a standardized care pathway to improve the early identification, prevention and treatment of infection in this patient group.As per NCCN recommendations this should include concurrent nasal and skin swabs, mupirocin ointment for nasal S. aureus carriage, routine herpes viral screening and the use of antiseptic techniques such as bleach baths, where appropriate.
A single-cell and spatially resolved atlas of human breast cancers
Authors: Sunny Z. Wu, Ghamdan Al-Eryani, Daniel Lee Roden, Simon Junankar, Kate Harvey, Alma Andersson, Aatish Thennavan, Chenfei Wang, James R. Torpy, Nenad Bartonicek, Taopeng Wang, Ludvig Larsson, Dominik Kaczorowski, Neil I. Weisenfeld, Cedric R. Uytingco, Jennifer G. Chew, Zachary W. Bent, Chia-Ling Chan, Vikkitharan Gnanasambandapillai, Charles-Antoine Dutertre, Laurence Gluch, Mun N. Hui, Jane Beith, Andrew Parker, Elizabeth Robbins, Davendra Segara, Caroline Cooper, Cindy Mak, Belinda Chan, Sanjay Warrier, Florent Ginhoux, Ewan Millar, Joseph E. Powell, Stephen R. Williams, X. Shirley Liu, Sandra O’Toole, Elgene Lim, Joakim Lundeberg, Charles M. Perou, Alexander Swarbrick
Journal: Nature Genetics (2021)
Prognostic value of polygenic risk scores for adults with psychosis
Authors: Isotta Landi, Deepak A. Kaji, Liam Cotter, Tielman Van Vleck, Gillian Belbin, Michael Preuss, Ruth J. F. Loos, Eimear Kenny, Benjamin S. Glicksberg, Noam D. Beckmann, Paul O’Reilly, Eric E. Schadt, Eric D. Achtyes, Peter F. Buckley, Douglas Lehrer, Dolores P. Malaspina, Steven A. McCarroll, Mark H. Rapaport, Ayman H. Fanous, Michele T. Pato, Carlos N. Pato, Tim B. Bigdeli, Girish N. Nadkarni, Alexander W. Charney
Journal: Nature Medicine (2021)
Allosteric Inhibition of HER2 by Moesin-Mimicking Compounds Targets HER2-Positive Cancers and Brain Metastases
Authors: Camille Faure, Rym Djerbi-Bouillié, Anaïs Domingot, Haniaa Bouzinba-Segard, Saïd Taouji, Yanis Saidi, Sandra Bernard, Floriane Carallis, Romy Rothe-Walther, Jean-Luc Lenormand, Eric Chevet, Sandrine Bourdoulous
Journal: Cancer Research (2021)

Therapies targeting the tyrosine kinase receptor HER2 have significantly improved survival of patients with HER2+ cancer. However, both de novo and acquired resistance remain a challenge, particularly in the brain metastatic setting. Here we report that, unlike other HER tyrosine kinase receptors, HER2 possesses a binding motif in its cytosolic juxtamembrane region that allows interaction with members of the Ezrin/Radixin/Moesin (ERM) family. Under physiologic conditions, this interaction controls the localization of HER2 in ERM-enriched domains and stabilizes HER2 in a catalytically repressed state. In HER2+ breast cancers, low expression of Moesin correlated with increased HER2 expression. Restoring expression of ERM proteins in HER2+ breast cancer cells was sufficient to revert HER2 activation and inhibit HER2-dependent proliferation. A high-throughput assay recapitulating the HER2-ERM interaction allowed for screening of about 1,500 approved drugs. From this screen, we found Zuclopenthixol, an antipsychotic drug that behaved as a Moesin-mimicking compound, because it directly binds the juxtamembrane region of HER2 and specifically inhibits HER2 activation in HER2+ cancers, as well as activation of oncogenic mutated and truncated forms of HER2. Zuclopenthixol efficiently inhibited HER2+ breast tumor progression in vitro and in vivo and, more importantly, showed significant activity on HER2+ brain tumor progression. Collectively, these data reveal a novel class of allosteric HER2 inhibitors, increasing the number of approaches to consider for intervention on HER2+ breast cancers and brain metastases. SIGNIFICANCE: This study demonstrates the functional role of Moesin in maintaining HER2 in a catalytically repressed state and provides novel therapeutic approaches targeting HER2+ breast cancers and brain metastasis using Moesin-mimicking compounds.
Abstract 20794: Prenatal Predictors of Urgent Postnatal Balloon Atrial Septostomy in Transposition of Great Arteries
Authors: Nita Ray Chaudhuri, Prasad Ravi, Lisa K Hornberger, Shanthi Sivanandam
Journal: Circulation (2016)

Nita Ray Chaudhuri, MD1, Prasad Ravi, MD2, Lisa K Hornberger, MD3, Shanthi Sivanandam, MD4 Background: Prenatal risk factors for poor outcomes in neonates with transposition of the great arteries a...
IgE cross-linking induces activation of human and mouse mast cell progenitors
Authors: Erika Méndez-Enríquez, Maya Salomonsson, Jens Eriksson, Christer Janson, Andrei Malinovschi, Mikael E. Sellin, Jenny Hallgren
Journal: Journal of Allergy and Clinical Immunology (2021)

The concept of innate and adaptive effector cells that are repleted by maturing inert progenitor cell populations is changing. Mast cells develop from rare mast cell progenitors populating peripheral tissues at homeostatic conditions, or as a result of induced recruitment during inflammatory conditions.Because FcεRI-expressing mast cell progenitors are the dominating mast cell type during acute allergic lung inflammation in vivo, we hypothesized that they are activated by IgE cross-linking.Mouse peritoneal and human peripheral blood cells were sensitized and stimulated with antigen, or stimulated with anti-IgE, and the mast cell progenitor population analyzed for signs of activation by flow cytometry. Isolated peritoneal mast cell progenitors were studied before and after anti-IgE stimulation at single-cell level by time-lapse fluorescence microscopy. Lung mast cell progenitors were analyzed for their ability to produce IL-13 by intracellular flow cytometry in a mouse model of ovalbumin-induced allergic airway inflammation.Sensitized mouse peritoneal mast cell progenitors demonstrate increased levels of phosphorylation of tyrosines on intracellular proteins (total tyrosine phosphorylation), and spleen tyrosine kinase (Syk) phosphorylation after antigen exposure. Anti-IgE induced cell surface-associated lysomal-associated membrane protein-1 (LAMP-1) in naive mast cell progenitors, and prompted loss of fluorescence signal and altered morphology of isolated cells loaded with lysotracker. In human mast cell progenitors, anti-IgE increased total tyrosine phosphorylation, cell surface-associated LAMP-1, and CD63. Lung mast cell progenitors from mice with ovalbumin-induced allergic airway inflammation produce IL-13.Mast cell progenitors become activated by IgE cross-linking and may contribute to the pathology associated with acute allergic airway inflammation.