tbuckley/cabot-search huggingface dataset:
An outbreak caused by the SARS-CoV-2 Delta variant (B.1.617.2) in a secondary care hospital in Finland, May 2021
Authors: Iivo Hetemäki, Sohvi Kääriäinen, Pirjo Alho, Janne Mikkola, Carita Savolainen-Kopra, Niina Ikonen, Hanna Nohynek, Outi Lyytikäinen
Journal: Eurosurveillance (2021)

An outbreak caused by the SARS-CoV-2 Delta variant (B.1.617.2) spread from one inpatient in a secondary care hospital to three primary care facilities, resulting in 58 infections including 18 deaths in patients and 45 infections in healthcare workers (HCW). Only one of the deceased cases was fully vaccinated. Transmission occurred despite the use of personal protective equipment by the HCW, as advised in national guidelines, and a high two-dose COVID-19 vaccination coverage among permanent staff members in the COVID-19 cohort ward.
Prompt changes in the plaque composition of a non-culprit coronary artery in patients with acute myocardial infarction : A virtual histolory study
Authors: H Funayama, Norifumi Kubo, Tomohiro Nakamura, Kenichi Sakakura, Takanori Yasu, San-e Ishikawa, Masanobu Kawakami, Shinichi Momomura
Journal: Circulation (2007)
PD1-1-1 Phase Ib study of BI 836880 (VEGF/Ang2 nanobody®) plus ezabenlimab (BI 754091, anti-PD-1 antibody) in patients with solid tumors
Authors: Nicolas Girard, Martin Wermke, Fabrice Barlesi, Dong-Wan Kim, Francois Ghiringhelli, Jaafar Bennouna, Thierry Lesimple, Enriqueta Felip, David Berz, Jong-Seok Lee, Harald Timotheus Landsteiner, Victoria Chen, Girish Jayadeva, Jurgen Alt, Bjorn Hackanson
Journal: Annals of Oncology (2021)
Double-endoscope assisted endoscopic submucosal dissection for treating gastric neuroendocrine tumor.
Authors: Jiaoyang Lu, Peng Wang, Rui Ji, Xuefeng Lu
Journal: Endoscopy (2021)

A middle-aged man was found to have a solitary lesion about 5 mm in diameter on the greater curvature of the lower gastric body during routine endoscopic examination ([Fig. 1 a]). Biopsy pathology plus immunohistochemistry reported a neuroendocrine tumor G2. A double-endoscope assisted endoscopic submucosal dissection (ESD) procedure was used to remove the tumor ([Video 1]).
Single Adrenal Metastasis From Prostate Cancer Detected by 68Ga-PSMA PET/CT and Confirmed by Biopsy
Authors: André Marcondes Braga Ribeiro, Eduardo Nóbrega Pereira Lima, Daniel Garcia, Stephania Martins Bezerra
Journal: Clinical Nuclear Medicine (2021)

Abstract This image demonstrates an unusual presentation of an adrenal metastasis from prostate cancer detected by 68 Ga–prostate-specific membrane antigen PET/CT and confirmed by biopsy. A 68-year-old man with prostate cancer persisted with elevated levels of prostate-specific antigen after radical prostatectomy. Imaging identified a single abnormal uptake in the left adrenal gland. A biopsy was performed showing a metastatic prostatic adenocarcinoma. The patient received systemic treatment, and his prostate-specific antigen level decreased significantly. Our objective is to illustrate an unusual and single site of prostate cancer metastasis, in which precise histological diagnosis was essential for correct clinical management of the patient.
Clinical patterns, recovery time and prolonged impact of COVID-19 illness in international athletes: the UK experience
Authors: James H Hull, Moses Wootten, Moiz Moghal, Neil Heron, Rhodri Martin, Emil S Walsted, Anita Biswas, Mike Loosemore, Niall Elliott, Craig Ranson
Journal: British Journal of Sports Medicine (2021)

To report COVID-19 illness pattern, symptom duration and time loss in UK elite athletes.Observational, clinical and database review of athletes with symptomatic COVID-19 illness managed within the UK Sports Institutes. Athletes were classified as confirmed (positive SARS-CoV-2 PCR or antibody tests) or probable (consistent clinical features) COVID-19. Clinical presentation was characterised by the predominant symptom focus (eg, upper or lower respiratory illness). Time loss was defined as days unavailable for full sport participation and comparison was made with a 2016-2019 respiratory illness dataset from the same surveillance system.Between 24 February 2020 and 18 January 2021, 147 athletes (25 Paralympic (17%)) with mean (SD) age 24.7 (5.2) years, 37% female, were diagnosed with COVID-19 (76 probable, 71 confirmed). Fatigue was the most prevalent symptom (57%), followed by dry cough (50%) and headache (46%). The median (IQR) symptom duration was 10 (6-17) days but 14% reported symptoms >28 days. Median time loss was 18 (12-30) days, with 27% not fully available >28 days from initial date of infection. This was greater than our historical non-COVID respiratory illness comparator; 6 days, 0-7 days (p<0.001) and 4% unavailable at 28 days. A lower respiratory phenotype (ie, including dyspnoea±chest pain±cough±fever) was present in 18% and associated with a higher relative risk of prolonged symptoms risk ratio 3.0 (95% CI: 1.4 to 6.5) and time loss 2.1 (95% CI: 1.2 to 3.5).In this cohort, COVID-19 largely resulted in a mild, self-limiting illness. The presence of lower respiratory tract features was associated with prolonged illness and a delayed return to sport.
Author Correction: A deep-learning pipeline for the diagnosis and discrimination of viral, non-viral and COVID-19 pneumonia from chest X-ray images
Authors: Guangyu Wang, Xiaohong Liu, Jun Shen, Chengdi Wang, Zhihuan Li, Linsen Ye, Xingwang Wu, Ting Chen, Kai Wang, Xuan Zhang, Zhongguo Zhou, Jian Yang, Ye Sang, Ruiyun Deng, Wenhua Liang, Tao Yu, Ming Gao, Jin Wang, Zehong Yang, Huimin Cai, Guangming Lu, Lingyan Zhang, Lei Yang, Wenqin Xu, Winston Wang, Andrea Olvera, Ian Ziyar, Charlotte Zhang, Oulan Li, Weihua Liao, Jun Liu, Wen Chen, Wei Chen, Jichan Shi, Lianghong Zheng, Longjiang Zhang, Zhihan Yan, Xiaoguang Zou, Guiping Lin, Guiqun Cao, Laurance L. Lau, Long Mo, Yong Liang, Michael Roberts, Evis Sala, Carola-Bibiane Schönlieb, Manson Fok, Johnson Yiu-Nam Lau, Tao Xu, Jianxing He, Kang Zhang, Weimin Li, Tianxin Lin
Journal: Nature Biomedical Engineering (2021)
Alternatives to traditional medical work experience for aspiring medical students
Authors: Kathryn Chia
Journal: BMJ (2021)

Aspiring medical students have always been encouraged to gain work experience to obtain a realistic understanding of what healthcare is really like, particularly the physical and emotional demands it makes.1 Work experience is also a way to develop characteristics, such as empathy and effective communication, that are indispensable to being a doctor (as set out in the NHS Constitution and explained in the Medical Schools Council guidance).2 These attributes can potentially be attained through non-clinical work experience too and should ideally be reflected on and showcased at interview. Work experience placements in healthcare settings are notoriously oversubscribed every year, and aspiring medics without family or social connections face increased barriers to accessing these placements. Furthermore, 2021 and 2022 applicants have had a particularly difficult time getting placements in hospitals because of the covid-19 pandemic.3 Alternatives to clinical work experience are therefore more important than ever, and it is vital that students understand how to engage with and reflect on non-clinical work experience. There are also many free virtual work experience opportunities available, allowing aspiring medics to learn more about medicine, the healthcare environment, and the structure of the NHS to overcome the barriers in attaining clinical work experience. Demonstrating an understanding of the core values expected in a doctor (such as teamwork, communication, and empathy) can be valuable in a medical school application. This can be helped by reflecting on your own life experiences, such as:
Engineering a safe monoclonal anti‐human IL‐2 that is effective in a murine model of food allergy and asthma
Authors: Martin Klein, Barbara Misme‐Aucouturier, Marie‐Aude Cheminant, Marion De Carvalho, Marie Wauters, Olivier Tranquet, Antoine Magnan, Grégory Bouchaud
Journal: Allergy (2021)

Abstract Background Regulatory T cells (Tregs) are known to protect against allergies. Moreover, the decrease in the frequency and efficiency of Tregs amplifies allergic symptoms. Aim This study investigated whether expanding Tregs in vivo with an IL‐2/IL‐2 antibody complex could be safe, well tolerated and efficient in a therapeutic setting in allergies. Methods We produced an anti‐IL‐2 antibody (1C6) and demonstrated that when it is complexed to human IL‐2, it increases IL‐2 efficiency to induce Tregs in vivo without any detectable side effects. Furthermore, the IL‐2/1C6 complex induces an increase in Helios expression by Tregs, suggesting that it not only elevated Treg numbers but also boosted their functions. Using mouse models of house‐dust‐mite‐induced airway inflammation and wheat‐gliadin‐induced food allergies, we investigated the therapeutic potential of the IL‐2/1C6 complex in allergies. Results IL‐2/1C6 treatment significantly reduced allergic symptoms, specific IgE production, the adaptive immune response and tissue damage. Interestingly, IL‐2/1C6 treatment modulated innate lymphoid cells by increasing ILC2s in asthma and decreasing ILC3s in food allergies. Conclusion In conclusion,complexed IL‐2/anti‐IL‐2 may restore Treg numbers and function in respiratory and food allergies, thereby improving allergic markers and symptoms. Our IL‐2/anti‐IL‐2 complex offers new hope for reestablishing immune tolerance in patients with allergies.
Lipocalin 2 as a link between ageing, risk factor conditions and age-related brain diseases
Authors: Doortje W. Dekens, Ulrich L.M. Eisel, Leonie Gouweleeuw, Regien G. Schoemaker, Peter P. De Deyn, Petrus J.W. Naudé
Journal: Ageing Research Reviews (2021)

Chronic (neuro)inflammation plays an important role in many age-related central nervous system (CNS) diseases, including Alzheimer's disease, Parkinson's disease and vascular dementia. Inflammation also characterizes many conditions that form a risk factor for these CNS disorders, such as physical inactivity, obesity and cardiovascular disease. Lipocalin 2 (Lcn2) is an inflammatory protein shown to be involved in different age-related CNS diseases, as well as risk factor conditions thereof. Lcn2 expression is increased in the periphery and the brain in different age-related CNS diseases and also their risk factor conditions. Experimental studies indicate that Lcn2 contributes to various neuropathophysiological processes of age-related CNS diseases, including exacerbated neuroinflammation, cell death and iron dysregulation, which may negatively impact cognitive function. We hypothesize that increased Lcn2 levels as a result of age-related risk factor conditions may sensitize the brain and increase the risk to develop age-related CNS diseases. In this review we first provide a comprehensive overview of the known functions of Lcn2, and its effects in the CNS. Subsequently, this review explores Lcn2 as a potential (neuro)inflammatory link between different risk factor conditions and the development of age-related CNS disorders. Altogether, evidence convincingly indicates Lcn2 as a key constituent in ageing and age-related brain diseases.
Telomerase Inhibition Impairs Self-Renewal of ß-Catenin Activated Myeloproliferative Neoplasm Progenitors
Authors: Wenxue Ma, Cayla Mason, Ping Chen, Qingfei Jiang, Nathan Delos Santos, Elisa Lazzari, Sheldon Morris, Phoebe Mondala, Jane Isquith, Fei Huang, Larissa Balaian, Catriona Jamieson
Journal: Blood (2017)
P-34 Real-world efficacy and safety of immune checkpoint inhibitors in microsatellite unstable or mismatch repair deficient gastrointestinal tumors
Authors: N. Martínez Lago, A. Cousillas Castiñeiras, A. Fernández Montes, B. Carnero Lopez, P. Gonzalez Villarroel, F. Vázquez-Rivera, B. Alonso de Castro, B. Gonzalez, M. Salgado Fernandez, E. Gallardo Martin, C. Reboredo Rendo, M. Mateos Gonzalez, J. de la Cámara Gomez, C. Romero Reinoso, J. Méndez Méndez
Journal: Annals of Oncology (2021)
A chemokine regulatory loop induces cholesterol synthesis in lung-colonizing triple-negative breast cancer cells to fuel metastatic growth
Authors: Bingchen Han, Felix Alonso-Valenteen, Zhe Wang, Nan Deng, Tian-Yu Lee, Bowen Gao, Ying Zhang, Yali Xu, Xinfeng Zhang, Sandrine Billet, Xuemo Fan, Stephen Shiao, Neil Bhowmick, Lali Medina-Kauwe, Armando Giuliano, Xiaojiang Cui
Journal: Molecular Therapy (2021)

Triple-negative breast cancer (TNBC) has a high propensity for organ-specific metastasis. However, the underlying mechanisms are not well understood. Here we show that the primary TNBC tumor-derived C-X-C motif chemokines 1/2/8 (CXCL1/2/8) stimulate lung-resident fibroblasts to produce the C-C motif chemokines 2/7 (CCL2/7), which, in turn, activate cholesterol synthesis in lung-colonizing TNBC cells and induce angiogenesis at lung metastatic sites. Inhibiting cholesterol synthesis in lung-colonizing breast tumor cells by pulmonary administration of simvastatin-carrying HER3-targeting nanoparticles reduces angiogenesis and growth of lung metastases in a syngeneic TNBC mouse model. Our findings reveal a novel, chemokine-regulated mechanism for the cholesterol synthesis pathway and a critical role of metastatic site-specific cholesterol synthesis in the pulmonary tropism of TNBC metastasis. The study has implications for the unresolved epidemiological observation that use of cholesterol-lowering drugs has no effect on breast cancer incidence but can unexpectedly reduce breast cancer mortality, suggesting interventions of cholesterol synthesis in lung metastases as an effective treatment to improve survival in individuals with TNBC. Triple-negative breast cancer (TNBC) has a high propensity for organ-specific metastasis. However, the underlying mechanisms are not well understood. Here we show that the primary TNBC tumor-derived C-X-C motif chemokines 1/2/8 (CXCL1/2/8) stimulate lung-resident fibroblasts to produce the C-C motif chemokines 2/7 (CCL2/7), which, in turn, activate cholesterol synthesis in lung-colonizing TNBC cells and induce angiogenesis at lung metastatic sites. Inhibiting cholesterol synthesis in lung-colonizing breast tumor cells by pulmonary administration of simvastatin-carrying HER3-targeting nanoparticles reduces angiogenesis and growth of lung metastases in a syngeneic TNBC mouse model. Our findings reveal a novel, chemokine-regulated mechanism for the cholesterol synthesis pathway and a critical role of metastatic site-specific cholesterol synthesis in the pulmonary tropism of TNBC metastasis. The study has implications for the unresolved epidemiological observation that use of cholesterol-lowering drugs has no effect on breast cancer incidence but can unexpectedly reduce breast cancer mortality, suggesting interventions of cholesterol synthesis in lung metastases as an effective treatment to improve survival in individuals with TNBC.
Ketamine-induced cholangiopathy in ARDS patients
Authors: Christian de Tymowski, François Dépret, Emmanuel Dudoignon, Matthieu Legrand, Vincent Mallet, Vincent Mallet, Kilian Bock, Paul Doumbe Mandengue, Nicolas Dufour, Jean-Damien Ricard, Pierre Isnard, Jean-Paul Duong Van Huyen, Jean-Michel Correas, Torsten Voigtländer, Vincent Frochot, Emmanuel Letavernier, Lucile Moga, Amandine Landrieux, Laurent Chouchana, Coralie Gernez, Carole Burger, Anne Scemla, Lionel Lamhaut, Rémi Flicoteau, Jean-Paul Duong Van Huyen, Jean-Michel Correas, Heiner Wedemeyer, Stanislas Pol
Journal: Intensive Care Medicine (2021)
Response to Comment on Ferrannini and Rosenstock. Clinical Translation of Cardiovascular Outcome Trials in Type 2 Diabetes: Is There More or Is There Less Than Meets the Eye? Diabetes Care 2021;44:641–646
Authors: Ele Ferrannini, Julio Rosenstock
Journal: Diabetes Care (2021)

Thank you for sharply spotting and kindly bringing to our attention an error in the units of event rates of the LEADER trial in Table 1 of our article (1). As you correctly surmise (2), we failed to notice the different units in this trial from the other trials, also due to the fact that we added trials as the manuscript went through rounds of revision. …
Medical–Financial Partnerships — Beyond Traditional Boundaries
Authors: Lucy E. Marcil, Katherine G. Barnett, Barry Zuckerman
Journal: New England Journal of Medicine (2021)

Interview with Dr. Lucy Marcil on the role of medical–financial partnerships in promoting individual and community health. (10:09)Download By directly addressing patients' financial status, including income, assets, and financial empowerment, clinicians can promote individual and community health. This issue is particularly relevant in the midst of the economic crisis associated with the Covid-19 pandemic.
Fluorescence Imaging and Photodynamic Inactivation of Bacteria Based on Cationic Cyclometalated Iridium(III) Complexes with Aggregation‐Induced Emission Properties
Authors: Po‐Yu Ho, Sin‐Ying Lee, Chuen Kam, Junfei Zhu, Guo‐Gang Shan, Yuning Hong, Wai‐Yeung Wong, Sijie Chen
Journal: Advanced Healthcare Materials (2021)

Abstract Antibacterial photodynamic therapy (PDT) is one of the emerging methods for curbing multidrug‐resistant bacterial infections. Effective fluorescent photosensitizers with dual functions of bacteria imaging and PDT applications are highly desirable. In this study, three cationic and heteroleptic cyclometalated Ir(III) complexes with the formula of [Ir(CˆN) 2 (NˆN)][PF 6 ] are prepared and characterized. These Ir(III) complexes named Ir(ppy) 2 bP , Ir(1‐pq) 2 bP, and Ir(2‐pq) 2 bP are comprised of three CˆN ligands (i.e., 2‐phenylpyridine (ppy), 1‐phenylisoquinoline (1‐pq), and 2‐phenylquinoline (2‐pq)) and one NˆN bidentate co‐ligand (bP). The photophysical characterizations demonstrate that these Ir(III) complexes are red‐emitting, aggregation‐induced emission active luminogens. The substitution of phenylpyridine with phenylquinoline isomers in the molecules greatly enhances their UV and visible‐light absorbance as well as the photoinduced reactive oxygen species (ROS) generation ability. All three Ir(III) complexes can stain both Gram‐positive and Gram‐negative bacteria efficiently. Interestingly, even though Ir(1‐pq) 2 bP and Ir(2‐pq) 2 bP are constitutional isomers with very similar structures and similar ROS generation ability in buffer, the former eradicates bacteria much more effectively than the other through white light‐irradiated photodynamic inactivation. This work will provide valuable information on the rational design of Ir(III) complexes for fluorescence imaging and efficient photodynamic inactivation of bacteria.
Plasma and ascites pharmacokinetics of meropenem in patients with decompensated cirrhosis and spontaneous bacterial peritonitis
Authors: Marie Griemsmann, Denis Grote-Koska, Markus Cornberg, Julius J. Schmidt, Benjamin Maasoumy, Thorsten Book, Birgit Bremer, Benjamin Schulte, Michael P. Manns, Heiner Wedemeyer, Korbinian Brand
Journal: Journal of Hepatology (2021)
Predicting critical state after COVID-19 diagnosis: model development using a large US electronic health record dataset
Authors: Mike D. Rinderknecht, Yannick Klopfenstein
Journal: npj Digital Medicine (2021)

Abstract As the COVID-19 pandemic is challenging healthcare systems worldwide, early identification of patients with a high risk of complication is crucial. We present a prognostic model predicting critical state within 28 days following COVID-19 diagnosis trained on data from US electronic health records (IBM Explorys), including demographics, comorbidities, symptoms, and hospitalization. Out of 15753 COVID-19 patients, 2050 went into critical state or deceased. Non-random train-test splits by time were repeated 100 times and led to a ROC AUC of 0.861 [0.838, 0.883] and a precision-recall AUC of 0.434 [0.414, 0.485] (median and interquartile range). The interpretability analysis confirmed evidence on major risk factors (e.g., older age, higher BMI, male gender, diabetes, and cardiovascular disease) in an efficient way compared to clinical studies, demonstrating the model validity. Such personalized predictions could enable fine-graded risk stratification for optimized care management.
Predicting Response to Programmed Cell Death Protein-1 or Programmed Death-Ligand 1 Blockade in NSCLC—Is Multiplex Immunohistochemistry or Immunofluorescence the Answer?
Authors: Wendy A. Cooper, Sylvie Lantuejoul, Mari Mino-Kenudson
Journal: Journal of Thoracic Oncology (2021)
Risdiplam-Treated Infants with Type 1 Spinal Muscular Atrophy versus Historical Controls
Authors: Basil T. Darras, Riccardo Masson, Maria Mazurkiewicz-Bełdzińska, Kristy Rose, Hui Xiong, Edmar Zanoteli, Giovanni Baranello, Claudio Bruno, Dmitry Vlodavets, Yi Wang, Muna El-Khairi, Marianne Gerber, Ksenija Gorni, Omar Khwaja, Heidemarie Kletzl, Renata S. Scalco, Paulo Fontoura, Laurent Servais
Journal: New England Journal of Medicine (2021)

Type 1 spinal muscular atrophy (SMA) is a progressive neuromuscular disease characterized by an onset at 6 months of age or younger, an inability to sit without support, and deficient levels of survival of motor neuron (SMN) protein. Risdiplam is an orally administered small molecule that modifies SMN2 pre-messenger RNA splicing and increases levels of functional SMN protein in blood.We conducted an open-label study of risdiplam in infants with type 1 SMA who were 1 to 7 months of age at enrollment. Part 1 of the study (published previously) determined the dose to be used in part 2 (reported here), which assessed the efficacy and safety of daily risdiplam as compared with no treatment in historical controls. The primary end point was the ability to sit without support for at least 5 seconds after 12 months of treatment. Key secondary end points were a score of 40 or higher on the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND; range, 0 to 64, with higher scores indicating better motor function), an increase of at least 4 points from baseline in the CHOP-INTEND score, a motor-milestone response as measured by Section 2 of the Hammersmith Infant Neurological Examination (HINE-2), and survival without permanent ventilation. For the secondary end points, comparisons were made with the upper boundary of 90% confidence intervals for natural-history data from 40 infants with type 1 SMA.A total of 41 infants were enrolled. After 12 months of treatment, 12 infants (29%) were able to sit without support for at least 5 seconds, a milestone not attained in this disorder. The percentages of infants in whom the key secondary end points were met as compared with the upper boundary of confidence intervals from historical controls were 56% as compared with 17% for a CHOP-INTEND score of 40 or higher, 90% as compared with 17% for an increase of at least 4 points from baseline in the CHOP-INTEND score, 78% as compared with 12% for a HINE-2 motor-milestone response, and 85% as compared with 42% for survival without permanent ventilation (P<0.001 for all comparisons). The most common serious adverse events were pneumonia, bronchiolitis, hypotonia, and respiratory failure.In this study involving infants with type 1 SMA, risdiplam resulted in higher percentages of infants who met motor milestones and who showed improvements in motor function than the percentages observed in historical cohorts. Longer and larger trials are required to determine the long-term safety and efficacy of risdiplam in infants with type 1 SMA. (Funded by F. Hoffmann-La Roche; FIREFISH ClinicalTrials.gov number, NCT02913482.).
Covid-19: US public health officials urge FDA to decide on booster vaccines
Authors: Janice Hopkins Tanne
Journal: BMJ (2021)

The vaccine advisory committee of the US Centers for Disease Control and Prevention (CDC) has expressed concern that the Food and Drug Administration has yet to decide whether immunocompromised people should receive booster shots of covid-19 vaccines.Some immunocompromised people "have taken matters into their own hands, and many are proceeding with additional doses of vaccine as they see fit," said Camille Kotton, committee member and a specialist in solid organ transplantation at Massachusetts General Hospital in Boston.