tbuckley/cabot-search huggingface dataset:
A Data Set and Deep Learning Algorithm for the Detection of Masses and Architectural Distortions in Digital Breast Tomosynthesis Images
Authors: Mateusz Buda, Ashirbani Saha, Ruth Walsh, Sujata Ghate, Nianyi Li, Albert Swiecicki, Joseph Y. Lo, Maciej A. Mazurowski
Journal: JAMA Network Open (2021)

Breast cancer screening is one of the most common radiological tasks with over 39 million exams performed each year. While breast cancer screening has been one of the most studied medical imaging applications of artificial intelligence, the development and evaluation of the algorithms are hindered due to the lack of well-annotated large-scale publicly available datasets. This is particularly an issue for digital breast tomosynthesis (DBT) which is a relatively new breast cancer screening modality. We have curated and made publicly available a large-scale dataset of digital breast tomosynthesis images. It contains 22,032 reconstructed DBT volumes belonging to 5,610 studies from 5,060 patients. This included four groups: (1) 5,129 normal studies, (2) 280 studies where additional imaging was needed but no biopsy was performed, (3) 112 benign biopsied studies, and (4) 89 studies with cancer. Our dataset included masses and architectural distortions which were annotated by two experienced radiologists. Additionally, we developed a single-phase deep learning detection model and tested it using our dataset to serve as a baseline for future research. Our model reached a sensitivity of 65% at 2 false positives per breast. Our large, diverse, and highly-curated dataset will facilitate development and evaluation of AI algorithms for breast cancer screening through providing data for training as well as common set of cases for model validation. The performance of the model developed in our study shows that the task remains challenging and will serve as a baseline for future model development.
Reply to Sundaram and Jagtap
Authors: Leena Kylänpää, Vilja Koskensalo, Marianne Udd, Juha Grönroos
Journal: Endoscopy (2021)

See also: Transpancreatic biliary sphincterotomy: justified or overkill?Endoscopy 2021; 53(09): 985-985DOI: 10.1055/a-1408-3258 See also: Transpancreatic biliary sphincterotomy versus double guidewire in difficult biliary cannulation: a randomized controlled trialEndoscopy 2021; 53(10): 1011-1019DOI: 10.1055/a-1327-2025
Apitd1, a nuclear protein with a histone-fold superfamily domain induces apoptosis in neuroblastoma cells
Authors: Cecilia Krona, Hanna Kryh, Katarina Ejeskar, Linda Olsson, Helena Caren, Rose-Marie Sjoberg, Tommy Martinsson
Journal: Cancer Research (2008)

3013  APITD1 is a novel gene in the neuroblastoma tumor suppressor candidate region on chromosome 1p36.2. Gene expression is down-regulated in primary neuroblastoma tumors from high-risk patients and cell growth is reduced by APITD1 overexpression. The purpose of this study was to determine the function of the encoded protein. A custom made antibody was used in Western blot analysis to detect proteins at the predicted molecular weight of 16 kDa. Purification by immunoprecipitation and mass spectrometry (MS/MS) analysis confirmed the identity of the Apitd1 protein. While expression of the APITD1 gene is relatively low in neuroblastoma cell lines compared to mRNA levels in a panel of normal tissues, the level of Apitd1 protein is not significantly reduced in neuroblastoma cell lines when compared to other cell lines. Apitd1 contains a predicted TFIID-31 domain, representing the TATA box-binding protein-associated factor, TAFII31, required for p53 mediated transcription activation. Although a large proportion of cells transfected with APITD1 enter apoptosis, protein levels of p53 and the p53 responsive genes Mdm2, p21WAF/CIP1 and Bax are unchanged by APITD1 overexpression, indicating that Apitd1 is not a factor required for p53-mediated transcription activation. The level of endogenous Apitd1 is correlated to p53 levels but not to expression of the anti-apoptotic protein Bcl2. This study also shows that the Apitd1 protein is preferably located to the nucleus, consistent with a recently published study, where Apitd1 was identified as a distal protein in the CENP-A centromeric complex. In conclusion, based on its cytogenetic location, 1p36.2, and its biological features in neuroblastoma tumors, APITD1 presents as a candidate neuroblastoma tumor suppressor gene. The encoded protein may be involved in transcriptional regulation of genes which control cell survival or it may be involved in chromosome alignment and segregation during mitosis. In this case, the absence of APITD1 expression in primary neuroblastoma tumors could cause errors of chromosome segregation which further leads to structural or numerical chromosomal aberrations.
TIL in Melanoma—Similar Approaches, Different Results, Unanswered Questions
Authors: Mario Sznol
Journal: Clinical Cancer Research (2021)

Abstract Prior treatment with anti-PD-1 and/or BRAF-targeted therapies was associated with limited activity of tumor infiltrating lymphocytes (TIL) in metastatic melanoma. Recent insights into mechanisms of action for TIL and anti-PD-1 provide the foundation for understanding differences in outcomes in different trials or populations, and a roadmap for developing improved products. See related article by Seitter et al., p. 5289
Gauging the impact of the COVID-19 pandemic on tuberculosis services: a global study
Authors: Giovanni Battista Migliori, Pei Min Thong, Jan-Willem Alffenaar, Justin Denholm, Marina Tadolini, Fatma Alyaquobi, François-Xavier Blanc, Danilo Buonsenso, Jin-Gun Cho, Luigi Ruffo Codecasa, Edvardas Danila, Raquel Duarte, José-María García-García, Gina Gualano, Adrian Rendon, Denise Rossato Silva, Mahamadou Bassirou Souleymane, Sai Meng Tham, Tania A. Thomas, Simon Tiberi, Zarir F. Udwadia, Delia Goletti, Rosella Centis, Lia D'Ambrosio, Giovanni Sotgiu, Catherine W.M. Ong
Journal: European Respiratory Journal (2021)

<b>This global study of 43 TB centres from 19 countries demonstrates the impact of COVID-19 pandemic on TB services. Newly diagnosed TB disease, drug-resistant TB, TB deaths, outpatient clinic attendances and newly diagnosed TB infection were reduced.</b>https://bit.ly/3sdHbfk
Inhaled isoflurane via the anaesthetic conserving device versus propofol for sedation of invasively ventilated patients in intensive care units in Germany and Slovenia: an open-label, phase 3, randomised controlled, non-inferiority trial
Authors: Andreas Meiser, Thomas Volk, Jan Wallenborn, Ulf Guenther, Tobias Becher, Hendrik Bracht, Konrad Schwarzkopf, Rihard Knafelj, Andreas Faltlhauser, Serge C Thal, Jens Soukup, Patrick Kellner, Matthias Drüner, Heike Vogelsang, Martin Bellgardt, Peter Sackey, Eberhard Barth, Tobias Becher, Berthold Bein, Martin Bellgardt, Paul Biever, Ralph Bogdanski, Hendrik Bracht, Sebastian Brandt, Matthias Drüner, Anreas Faltlhauser, Arnim Geise, Adrian Iustin Georgevici, Philipp Gude, Ulf Guenther, Uwe Hamsen, Christian Hönemann, Patrick Kellner, Kerstin Kellner, Azzeddine Kermad, Rihard Knafelj, Klaus Kogelmann, Rainer Kram, Andrej Markota, Werner Meermeier, Andreas Meiser, Matej Podbregar, Peter Sackey, Patrick Schramm, Matthias Schroeder, Konrad Schwarzkopf, Jens Soukup, Serge C Thal, Heike Vogelsang, Thomas Volk, Jan Wallenborn, Christian Waydhas, Norbert Weiler, Richard Wetzold
Journal: The Lancet Respiratory Medicine (2021)
Therapeutic strategies in METex14 skipping mutated non-small cell lung cancer
Authors: Leylah M. Drusbosky, Richa Dawar, Estelamari Rodriguez, Chukwuemeka V. Ikpeazu
Journal: Journal of Hematology & Oncology (2021)

Abstract METex14 skipping mutations occur in about 3–4% of lung adenocarcinoma patients and 1–2% of patients with other lung cancer histology. The MET receptor tyrosine kinase and its ligand hepatocyte growth factor (HGF) are established oncogenic drivers of NSCLC. A mutation that results in loss of exon 14 in the MET gene leads to dysregulation and inappropriate signaling that is associated with increased responsiveness to MET TKIs. Results from GEOMETRY mono-1 and VISION Phase I/II clinical trials demonstrated significant clinical activity in patients treated with the MET Exon 14 skipping mutation inhibitors capmatinib and tepotinib with tolerable toxicity profile. In the GEOMETRY mono-1 trial, capmatinib was especially active in treatment-naïve patients supporting the upfront testing of this oncogenic driver. Tepotinib demonstrated superior activity in the pretreated patients in the VISION trial. Savolitinib is another MET TKI that has shown efficacy in the first- and second-line settings, including patients with aggressive pulmonary sarcomatoid carcinoma. These studies have demonstrated that these TKIs can cross the blood brain barrier and demonstrated some activity toward CNS metastases. MET Exon 14 skipping mutation is detected by NGS-based testing of liquid or tissue biopsies, with preference for RNA-based NGS. The activity of capmatinib and tepotinib is limited by the development of acquired resistance. Current research is focused on strategies to overcome resistance and improve the effectiveness of these agents. Our aim is to review the current status of MET Exon 14 skipping mutation as it pertains NSCLC.
26887 Effect of ruxolitinib cream on sleep disturbance and sleep impairment: Pooled analysis from two randomized phase 3 studies
Authors: Eric L. Simpson, Mark Boguniewicz, Diamant Thaçi, Laurent Misery, Jonathan I. Silverberg, Lisa A. Beck, Michael E. Kuligowski, May E. Venturanza, Kang Sun, Jacek C. Szepietowski
Journal: Journal of the American Academy of Dermatology (2021)
25933 Tirbanibulin ointment 1% for actinic keratosis (AK): Pooled data from two phase 3 studies
Authors: Andrew Blauvelt, Steven Kempers, Todd Schleisinger, Edward Lain, Hui Wang, David Cutler, Mark Lebwohl, Jane Fang, Rudolf Kwan
Journal: Journal of the American Academy of Dermatology (2021)
Selonsertib in adults with pulmonary arterial hypertension (ARROW): a randomised, double-blind, placebo-controlled, phase 2 trial
Authors: Stephan Rosenkranz, Jeremy Feldman, Vallerie V McLaughlin, Franz Rischard, Tobias J Lange, R James White, Andrew J Peacock, Felix Gerhardt, Ramin Ebrahimi, Gabriel Brooks, Carol Satler, Robert P Frantz
Journal: The Lancet Respiratory Medicine (2021)
The self-peptide repertoire plays a critical role in transplant tolerance induction
Authors: Eric T. Son, Pouya Faridi, Moumita Paul-Heng, Mario L. Leong, Kieran English, Sri H. Ramarathinam, Asolina Braun, Nadine L. Dudek, Ian E. Alexander, Leszek Lisowski, Patrick Bertolino, David G. Bowen, Anthony W. Purcell, Nicole A. Mifsud, Alexandra F. Sharland
Journal: Journal of Clinical Investigation (2021)

While direct allorecognition underpins both solid organ allograft rejection and tolerance induction, the specific molecular targets of most directly alloreactive CD8+ T cells have not been defined. In this study, we used a combination of genetically engineered major histocompatibility complex class I (MHC I) constructs, mice with a hepatocyte-specific mutation in the class I antigen-presentation pathway, and immunopeptidomic analysis to provide definitive evidence for the contribution of the peptide cargo of allogeneic MHC I molecules to transplant tolerance induction. We established a systematic approach for the discovery of directly recognized pMHC epitopes and identified 17 strongly immunogenic H-2Kb-associated peptides recognized by CD8+ T cells from B10.BR (H-2k) mice, 13 of which were also recognized by BALB/c (H-2d) mice. As few as 5 different tetramers used together were able to identify a high proportion of alloreactive T cells within a polyclonal population, suggesting that there are immunodominant allogeneic MHC-peptide complexes that can account for a large component of the alloresponse.
Doctors call for ban on virginity testing and hymenoplasty
Authors: Gareth Iacobucci
Journal: BMJ (2021)

The Royal College of Obstetricians and Gynaecologists (RCOG) has urged the government to introduce a ban on virginity testing and hymenoplasty in the UK.

In a policy statement published on 16 August, the college said there is no medical reason why virginity testing, hymenoplasty, or any other procedure under a different name that seeks to reconstruct or repair the hymen would need to be carried out. It said such procedures were harmful as they create and exacerbate social, cultural, and political beliefs that a woman’s value is based on whether or not she is a virgin before marriage.

The college noted that the scale of the …
Group IIA secreted phospholipase A2 is associated with the pathobiology leading to COVID-19 mortality
Authors: Justin M. Snider, Jeehyun Karen You, Xia Wang, Ashley J. Snider, Brian Hallmark, Manja M. Zec, Michael C. Seeds, Susan Sergeant, Laurel Johnstone, Qiuming Wang, Ryan Sprissler, Tara F. Carr, Karen Lutrick, Sairam Parthasarathy, Christian Bime, Hao Helen Zhang, Chiara Luberto, Richard R. Kew, Yusuf A. Hannun, Stefano Guerra, Charles E. McCall, Guang Yao, Maurizio Del Poeta, Floyd H. Chilton
Journal: Journal of Clinical Investigation (2021)

There is an urgent need to identify the cellular and molecular mechanisms responsible for severe COVID-19 that results in death. We initially performed both untargeted and targeted lipidomics as well as focused biochemical analyses of 127 plasma samples and found elevated metabolites associated with secreted phospholipase A2 (sPLA2) activity and mitochondrial dysfunction in patients with severe COVID-19. Deceased COVID-19 patients had higher levels of circulating, catalytically active sPLA2 group IIA (sPLA2-IIA), with a median value that was 9.6-fold higher than that for patients with mild disease and 5.0-fold higher than the median value for survivors of severe COVID-19. Elevated sPLA2-IIA levels paralleled several indices of COVID-19 disease severity (e.g., kidney dysfunction, hypoxia, multiple organ dysfunction). A decision tree generated by machine learning identified sPLA2-IIA levels as a central node in the stratification of patients who died from COVID-19. Random forest analysis and least absolute shrinkage and selection operator-based (LASSO-based) regression analysis additionally identified sPLA2-IIA and blood urea nitrogen (BUN) as the key variables among 80 clinical indices in predicting COVID-19 mortality. The combined PLA-BUN index performed significantly better than did either one alone. An independent cohort (n = 154) confirmed higher plasma sPLA2-IIA levels in deceased patients compared with levels in plasma from patients with severe or mild COVID-19, with the PLA-BUN index-based decision tree satisfactorily stratifying patients with mild, severe, or fatal COVID-19. With clinically tested inhibitors available, this study identifies sPLA2-IIA as a therapeutic target to reduce COVID-19 mortality.
Light Chain Deposition Disease: An Unusual Cause of Portal Hypertension
Authors: Molly Delk Plummer, Fredric Regenstein
Journal: Hepatology (2021)

Light chain deposition disease (LCDD) is a rare entity that is generally discovered in the setting of solid organ dysfunction. The monoclonal gammopathy leads to abnormal deposition of light chains in tissues, most often manifested by way of renal dysfunction. Other organ systems may also be affected, the liver being the second‐most common after the kidneys. Liver involvement rarely leads to clinically significant disease, with few case reports in the literature. We present the case of a patient referred to a hepatology clinic for the evaluation of new‐onset ascites resulting from portal hypertension secondary to LCDD involving the liver.
Abstract 18131: Elevated High-sensitivity C-reactive Protein as a Risk Factor for Adverse Outcomes of Hypertrophic Cardiomyopathy
Authors: Ling Zhu, Tao Tian, Jizheng Wang, Kai Sun, Yilu Wang, Hongju Zhang, Hu Shen, Xiaojian Wang, Yubao Zou, Rutai Hui, Zuyi Yuan, Lei Song
Journal: Circulation (2012)

Background: Hypertrophic cardiomyopathy (HCM) is a clinically heterogeneous disease with a diverse prognosis. Recent studies suggest that inflammatory response may play a significant role in the ph...
Percutaneous radiofrequency thermal ablation for hepatocellular carcinoma results in more complete necrosis but location and size of the tumor influence local therapeutic effects.
Authors: Komorizono Y, Yamasaki N, Hiwaki T, Shibatoh T, Sako K, Maeda M, Kohara K, Imamura Y, Baba Y, Oketani M, Ishibashi K, Arima T
Journal: Hepatology (2001)
SO-26 In-silico Lynch syndrome-related neoantigens prediction for a dendritic cell-based cancer prevention vaccine
Authors: C. Bayó, G. Castellano, T. Ocaña, L. Moreira, S. Carballal, A. Sánchez, R. Moreira, O. Ortiz, A. Castells, M. Pellisé, M. Juan-Otero, D. Benitez-Ribas, F. Balaguer
Journal: Annals of Oncology (2021)
Author Correction: Inhibition of hypoxia-inducible factor-2α in renal cell carcinoma with belzutifan: a phase 1 trial and biomarker analysis
Authors: Toni K. Choueiri, Todd M. Bauer, Kyriakos P. Papadopoulos, Elizabeth R. Plimack, Jaime R. Merchan, David F. McDermott, M. Dror Michaelson, Leonard J. Appleman, Sanjay Thamake, Rodolfo F. Perini, Naseem J. Zojwalla, Eric Jonasch
Journal: Nature Medicine (2021)
Manganese Ferrite Nanoparticles Encapsulated into Vitamin E/Sphingomyelin Nanoemulsions as Contrast Agents for High‐Sensitive Magnetic Resonance Imaging
Authors: Sandra Díez‐Villares, Miguel A. Ramos‐Docampo, Andrés da Silva‐Candal, Pablo Hervella, Abi J. Vázquez‐Ríos, Ana B. Dávila‐Ibáñez, Rafael López‐López, Ramón Iglesias‐Rey, Verónica Salgueiriño, María de la Fuente
Journal: Advanced Healthcare Materials (2021)

Abstract Magnetic resonance imaging (MRI) is one of the most powerful non‐invasive imaging modalities used in clinics due to its great spatial resolution and excellent soft‐tissue contrast, though still less sensitive than other techniques such as the nuclear imaging modalities. This lack of sensitivity can be improved with the use of contrast agents based on nanomaterials. In recent years, researchers have focused on the development of magnetic nanoparticles, given their role as enhancers of the contrast signal based on the magnetic resonance. Manganese ferrite nanoparticles stand out, given their high magnetic susceptibility and magnetic soft nature. Herein, 10 nm MnFe 2 O 4 nanoparticles, functionalized with the natural antioxidant vitamin E (VitE‐MFO) are encapsulated into simple, biodegradable and non‐toxic nanoemulsions (NEs), by a reproducible one‐step method obtaining stable 150 nm‐sized magnetic nanoemulsions (VitE‐MFO‐NEs). After encapsulation, the superparamagnetic properties of VitE‐MFO are maintained and MR imaging studies reveal an extremely high transverse relaxivity for VitE‐MFO‐NEs (652.9 × 10 −3 m −1 s −1 ), twofold higher than VitE‐MFO value. Moreover, VitE‐MFO‐NEs show great in vivo biocompatibility and good signal in in vivo and ex vivo MRI, which indicates their great potential for biomedical imaging enhancing the negative MR contrast and significantly improving the sensitivity of MRI.
Retrotransposons as pathogenicity factors of the plant pathogenic fungus Botrytis cinerea
Authors: Antoine Porquier, Constance Tisserant, Francisco Salinas, Carla Glassl, Lucas Wange, Wolfgang Enard, Andreas Hauser, Matthias Hahn, Arne Weiberg
Journal: Genome biology (2021)

Abstract Background Retrotransposons are genetic elements inducing mutations in all domains of life. Despite their detrimental effect, retrotransposons can become temporarily active during epigenetic reprogramming and cellular stress response, which may accelerate host genome evolution. In fungal pathogens, a positive role has been attributed to retrotransposons when shaping genome architecture and expression of genes encoding pathogenicity factors; thus, retrotransposons are known to influence pathogenicity. Results We uncover a hitherto unknown role of fungal retrotransposons as being pathogenicity factors, themselves. The aggressive fungal plant pathogen, Botrytis cinerea , is known to deliver some long-terminal repeat (LTR) deriving regulatory trans-species small RNAs ( Bc sRNAs) into plant cells to suppress host gene expression for infection. We find that naturally occurring, less aggressive B. cinerea strains possess considerably lower copy numbers of LTR retrotransposons and had lost retrotransposon Bc sRNA production. Using a transgenic proof-of-concept approach, we reconstitute retrotransposon expression in a Bc sRNA-lacking B. cinerea strain, which results in enhanced aggressiveness in a retrotransposon and Bc sRNA expression-dependent manner. Moreover, retrotransposon expression in B. cinerea leads to suppression of plant defence-related genes during infection. Conclusions We propose that retrotransposons are pathogenicity factors that manipulate host plant gene expression by encoding trans-species Bc sRNAs. Taken together, the novelty that retrotransposons are pathogenicity factors will have a broad impact on studies of host-microbe interactions and pathology.
SARS-CoV-2 Infections and Hospitalizations Among Persons Aged ≥16 Years, by Vaccination Status — Los Angeles County, California, May 1–July 25, 2021
Authors: Jennifer B. Griffin, Meredith Haddix, Phoebe Danza, Rebecca Fisher, Tae Hee Koo, Elizabeth Traub, Prabhu Gounder, Claire Jarashow, Sharon Balter
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

COVID-19 vaccines fully approved or currently authorized for use through Emergency Use Authorization from the Food and Drug Administration are critical tools for controlling the COVID-19 pandemic; however, even with highly effective vaccines, a proportion of fully vaccinated persons will become infected with SARS-CoV-2, the virus that causes COVID-19 (1).To characterize postvaccination infections, the Los Angeles County Department of Public Health (LACDPH) used COVID-19 surveillance and California Immunization Registry 2 (CAIR2) data to describe age-adjusted infection and hospitalization rates during May 1-July 25, 2021, by vaccination status.Whole genome sequencing (WGS)-based SARS-CoV-2 lineages and cycle threshold (Ct) values from qualitative reverse transcription-polymerase chain reaction (RT-PCR) for two SARS-CoV-2 gene targets, including the nucleocapsid (N) protein gene region and the open reading frame 1 ab (ORF1ab) polyprotein gene region,* were reported for a convenience sample of specimens.Among 43,127 reported SARS-CoV-2 infections in Los Angeles County residents aged ≥16 years, 10,895 (25.3%) were in fully vaccinated persons, 1,431 (3.3%) were in partially vaccinated persons, and 30,801 (71.4%) were in unvaccinated persons.Much lower percentages of fully vaccinated persons infected with SARS-CoV-2 were hospitalized (3.2%), were admitted to an intensive care unit (0.5%), and required mechanical ventilation (0.2%) compared with partially vaccinated persons (6.2%, 1.0%, and 0.3%, respectively) and unvaccinated persons (7.6%, 1.5%, and 0.5%, respectively) (p<0.001 for all comparisons).On July 25, the SARS-CoV-2 infection rate among unvaccinated persons was 4.9 times and the hospitalization rate was 29.2 times the rates among fully vaccinated persons.During May 1-July 25, the percentages of B.1.617.2 (Delta) variant infections estimated from 6,752 samples with lineage data increased among fully vaccinated persons (from 8.6% to 91.2%), partially vaccinated persons (from 0% to 88.1%), and unvaccinated persons (from * Gene targets for RT-PCR testing included the N protein gene region and the ORF1ab polyprotein gene region.The N gene targets were analyzed separately for two laboratories because Ct values are not directly comparable across different testing laboratories; these N gene targets were designated SARS-CoV-2 nucleocapsid (SC2N) and N to differentiate between the two participating laboratory partners.Gene targets were selected based on testing platforms used by LACDPH laboratory partners.