tbuckley/cabot-search huggingface dataset:
Mako: A Graph-Based Pattern Growth Approach to Detect Complex Structural Variants
Authors: Jiadong Lin, Xiaofei Yang, Walter Kosters, Tun Xu, Yanyan Jia, Songbo Wang, Qihui Zhu, Mallory Ryan, Li Guo, Mark B. Gerstein, Ashley D. Sanders, Micheal C. Zody, Michael E. Talkowski, Ryan E. Mills, Jan O. Korbel, Tobias Marschall, Peter Ebert, Peter A. Audano, Bernardo Rodriguez-Martin, David Porubsky, Marc Jan Bonder, Arvis Sulovari, Jana Ebler, Weichen Zhou, Rebecca Serra Mari, Feyza Yilmaz, Xuefang Zhao, PingHsun Hsieh, Joyce Lee, Sushant Kumar, Tobias Rausch, Yu Chen, Zechen Chong, Katherine M. Munson, Mark J.P. Chaisson, Junjie Chen, Xinghua Shi, Aaron M. Wenger, William T. Harvey, Patrick Hansenfeld, Allison Regier, Ira M. Hall, Paul Flicek, Alex R. Hastie, Susan Fairely, Chengsheng Zhang, Charles Lee, Scott E. Devine, Evan E. Eichler, Kai Ye
Journal: Genomics Proteomics & Bioinformatics (2021)

Complex structural variants (CSVs) are genomic alterations that have more than two breakpoints and are considered as the simultaneous occurrence of simple structural variants. However, detecting the compounded mutational signals of CSVs is challenging through a commonly used model-match strategy. As a result, there has been limited progress for CSV discovery compared with simple structural variants. Here, we systematically analyzed the multi-breakpoint connection feature of CSVs, and proposed Mako, utilizing a bottom-up guided model-free strategy, to detect CSVs from paired-end short-read sequencing. Specifically, we implemented a graph-based pattern growth approach, where the graph depicts potential breakpoint connections, and pattern growth enables CSV detection without pre-defined models. Comprehensive evaluations on both simulated and real datasets revealed that Mako outperformed other algorithms. Notably, validation rates of CSVs on real data based on experimental and computational validations as well as manual inspections are around 70%, where the medians of experimental and computational breakpoint shift are 13 bp and 26 bp, respectively. Moreover, the Mako CSV subgraph effectively characterized the breakpoint connections of a CSV event and uncovered a total of 15 CSV types, including two novel types of adjacent segment swap and tandem dispersed duplication. Further analysis of these CSVs also revealed the impact of sequence homology on the formation of CSVs. Mako is publicly available at https://github.com/xjtu-omics/Mako.
Diagnostic Radionuclides Labeled on Biomimetic Nanoparticles for Enhanced Follow‐Up Photothermal Therapy of Cancer
Authors: Xuan Yi, Mengling Shen, Xinpei Liu, Jingyu Gu, Zewei Jiang, Lixing Xu, Kai Yang
Journal: Advanced Healthcare Materials (2021)

Abstract Imaging‐guided local therapy is the most effective strategy to treat primary cancers in patients. However, the local therapeutic effect should be further improved under the premise of absence of induction of additional side effects. It would be meaningful to analyze the potential assistance of nuclear imaging to the follow‐up treatments. In this study,cancer‐targeted copper sulfide nanoparticles with 99m Tc labeling ( 99m Tc‐M‐CuS‐PEG) are prepared using‐cancer cell membranes as a synthesis reactor and applied for the potential single‐photon emission computed tomography/photoacoustic imaging‐guided and 99m Tc‐amplified photothermal therapy of cancer. Owing to the homologous targeting capability of the cancer cell membrane, M‐CuS‐PEG selectively accumulates in homologous tumor sites. After labeling with 99m Tc, M‐CuS‐PEG with a high near‐infrared light absorbance can realize bimodal imaging‐guided photothermal therapy of cancer. Furthermore, the labeled 99m Tc significantly enhances the cell uptake of M‐CuS‐PEG by inducing G2/M arrest of the cell cycle, further improving the photothermal antitumor effect, which is positively correlated with endocytosis of the photothermal conversion reagent. Therefore, a novel cancer‐targeted theranostic nanoplatform is developed and it is revealed that the labeled 99m Tc can not only guide but also amplify the subsequent therapy of cancer, providing a conceptual strategy for cancer theranostics with a high biosafety.
Secretory otitis media: the Cantekin affair
Authors: J. L. Wilson
Journal: JAMA (1992)

To the Editor.  —I appreciate the study by Cantekin et al 1 confirming what many of us in primary care have observed: namely, that chronic and recurrent otitis media does not respond to antibiotics. The liberal and sometimes indiscriminate use of antibiotics that are frequently prescribed by physicians can lead to, among many other problems, the often unrecognized but common condition of intestinal microbial dysbiosis and the many symptoms associated with this. 2,3   This article should encourage us to be more open to understanding the cause of this condition. In 1983, Green 4 outlined the relationship between diet and otitis media. In 1975, Viscomi 5 discussed the relationship between environmental influences, particularly diet, and eustachian tube dysfunction leading to middle-ear effusions and subsequent otitis. Two important articles appeared in 1990 that emphasized this relationship between otitis media and environmental factors. Hurst 6 published a study of 20 patients with long-term
Changes in Use of Respiratory Support for Preterm Infants in the US, 2008-2018
Authors: L. Dupree Hatch, Reese H. Clark, Waldemar A. Carlo, Ann R. Stark, E. Wesley Ely, Stephen W. Patrick
Journal: JAMA Pediatrics (2021)

In preterm infants, mechanical ventilation (MV) is associated with adverse pulmonary and neurodevelopmental outcomes. Multiple randomized clinical trials over the past 2 decades have shown the effectiveness of early noninvasive ventilation (NIV) in decreasing the use of MV in preterm infants. The epidemiologic factors associated with respiratory support in US preterm infants and any temporal changes after these trials is unknown.To evaluate temporal changes in MV and noninvasive respiratory support in US preterm infants.In a cohort design, 2 large national data sets (Pediatrix Clinical Data Warehouse for the clinical cohort and National Inpatient Sample for the national cohort) were used to collect data on preterm infants (<35 weeks' gestation) without congenital anomalies who received active intensive care and were discharged home or died in the birth hospital from January 1, 2008, to December 31, 2018. Data analysis was conducted from December 10, 2019, to December 16, 2020.Discharge year.In the clinical cohort, detailed respiratory support data were generated, including days of MV and NIV modalities, and temporal trends were evaluated using multivariable modified Poisson or negative binomial regression models with discharge year as a continuous variable. In the national cohort, observed and expected national MV use were calculated.Among 259 311 infants (47.2% female) in 359 neonatal intensive care units in the clinical cohort, decreases were noted in the use (from 29.4% of infants in 2008 to 18.5% in 2018, relative risk for annual change, 0.96; 95% CI, 0.95-0.96) and duration (mean days, from 10.3 in 2008 to 9.7 in 2018; rate ratio for annual change, 0.98; 95% CI, 0.97-0.98) of MV. Noninvasive ventilation use increased from 57.9% of infants in 2008 to 67.4% in 2018 (adjusted relative risk for annual change, 1.02; 95% CI, 1.02-1.03), and mean NIV duration increased by 3.2 days (95% CI, 2.9-3.6 days). With increased use of continuous positive airway pressure and nasal intermittent positive-pressure ventilation as the main factors in the increase, the mean duration of respiratory support increased from 13.8 to 15.4 days (adjusted rate ratio for annual change, 1.03; 95% CI, 1.02-1.04) from 2008 to 2018. Among 1 169 441 infants in the national cohort, MV use decreased from 22.0% in 2008 to 18.5% in 2018, with an estimated 29 700 fewer ventilated infants and 142 000 fewer days of MV than expected during this period.These findings suggest that preterm respiratory support changed significantly from 2008 to 2018, with decreased use and duration of MV, increased use and duration of NIV, and an overall increase in respiratory support duration.
Abstract 2371: MicroRNA-99b-5p targets the mTOR/AR axis and induced autophagic cell death in prostate cancer cells
Authors: Suryakant Niture, Lucas Tricoli, Kala Hayes, Deepak Kumar
Journal: Cancer Research (2021)

Abstract MicroRNAs are the small non-coding regulatory RNA molecules involved in a wide array of cellular and molecular processes. MicroRNAs negatively regulate gene expression via base-pairing with complementary sequences within mRNA molecules. In cancer, the dysregulation of miRNAs expression is associated with cancer development or suppression through the regulation of key gene expression followed by modulation of multiple cell signaling pathways. In the present study, we investigated the role of microRNA-99b-5p (miR-99b) on prostate cancer (PCa) cell survival, cell migration, and apoptosis. Overexpression of miR-99b in PCa cells inhibited cell proliferation, cell colony-forming capability, spheroid formation, and induced cell apoptosis. On the contrary, inactivation of miR-99b by miR-99b inhibitor promotes PCa cell proliferation, cell colony-forming capability, and cell migration. Mechanistically, miR-99b binds with the 3'UTR region of the mammalian target of the rapamycin (mTOR) gene and controls the expression of mTOR. Our preliminary data also suggest that miR-99b also inhibits androgen receptor (AR) activity in LNCaP cells and induced cell apoptosis. Further by inhibition of mTOR, miR-99b induced autophagy in PCa cells and autophagic cell death. Expression of miR-99b and inactivation of mTOR by rapamycin increased the sensitivity of PCa cells to anti-PCa drug docetaxel (DTX). Collectively the data suggest that miR-99b functions as a tumor suppressor in PCa cells, and therefore, miR-99b may be considered as novel biomarkers and therapeutic targets for PCa management in PCa patients. Citation Format: Suryakant Niture, Lucas Tricoli, Kala Hayes, Deepak Kumar. MicroRNA-99b-5p targets the mTOR/AR axis and induced autophagic cell death in prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2371.
First qualitative study into comprehensibility of IPSS and 2 visual alternatives for men with adequate and men with limited health literacy skills, leading to a new, better understood alternative: Dutch Reduced Illustrated Prostate Symptom Score (DRIPSS)
Authors: F.W.M. Schlatmann, M.R. Van Balken, A.F. Winter, I-J. De Jong, C.J.M. Jansen
Journal: European Urology (2021)
A Meta-Analysis of the Prognostic Accuracy of Clinical Prediction Rules for Post-Pulmonary Embolism Mortality in Patients with Cancer
Authors: Jonathan Caranfa, Christine G. Kohn, Gary H. Lyman, Nicole M. Kuderer, Catherine Stirbis, Mark Wysocki, Craig I. Coleman, Erin R Weeda, Elaine Nguyen
Journal: Blood (2017)
Abstract 724: FE65 in breast cancer patients and its clinicopathological significance
Authors: Junyao Xu, Erina Iwabuchi, Yasuhiro Miki, Ayako Kanai, Takanori Ishida, Hironobu Sasano
Journal: Cancer Research (2021)

Abstract FE65 is well known to bind with amyloid precursor protein (APP), translocate FE65-APP complex into nucleus and modulate gene transcription. APP was reported to be closely associated with breast cancer progression but clinical significance of FE65 has remained virtually unknow. We first studied 88 surgical pathology specimens with their clinicopathological factors. Results showed nuclear FE65 immunoreactivity was significant positively correlated with estrogen receptor (ER) status (P=0.054) and inversely with histological grade of the patients(P=0.038). We then analyzed 145 ER positive cases which include 44 ductal carcinomas in situ (DCIS) cases and 101 invasive ductal carcinoma (IDC) cases. The number of FE65 positive carcinoma cells was significantly higher in IDC than DCIS (P=0.0395). We then performed in vitro wound healing assay, which demonstrated that FE65 knock-down cells migrated slower than control groups (P=0.0495). FE65 formed the complex with APP and in order to further elucidate their detailed intracellular binding status, proximity ligation assay (PLA) was employed. Binding of APP and FE65 was detected in the cytoplasm with that of ER and FE65 in the nucleus. These results demonstrated that FE65 first bound to APP in the cytoplasm and was then released into the nucleus after phosphorylation of APP. This released FE65 in the nuclei could interact with ER to promote cell migration. Based on those results above, we then conducted the WST-8 assay to further elucidate the possible involvement of FE65 in cell survival. FE65 influenced response of tamoxifen in breast carcinoma cells, and the survival rate of those knocked down by FE65 siRNA was significantly higher than that of the control siRNA group(P=0.0039), indicating that FE65 could contribute to increase the sensitivity of tamoxifen action.In summary, FE65 was demonstrated to stimulate cell proliferation and migration, possibly as a result of the interaction of FE65 with APP in the cytoplasm and ER in the nuclei. In addition, FE65 could enhance the actions of tamoxifen by increasing ER expression and subsequent availability of its binding to ER. Citation Format: Junyao Xu, Erina Iwabuchi, Yasuhiro Miki, Ayako Kanai, Takanori Ishida, Hironobu Sasano. FE65 in breast cancer patients and its clinicopathological significance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 724.
Prabhu Dayal Nigam
Authors: Nikhil Kaushik, Renuka Kaul-Nigam
Journal: BMJ (2021)

After a Commonwealth fellowship at Guy’s Hospital in London, Prabhu Dayal returned to Lady Harding Medical College and associated Willingdon Hospital (now Ram Manohar Lohia Hospital) in 1968. He set up the cardiology department …
右室流出路起源心室頻拍に対してNon-contact mapping法が有用であった1例
Authors: 木村征靖, 小川宏, 分山隆敏, 高木昭, 岩見孝景, 波多野靖幸, 宮崎要介, 平塚淳史, 松田朋子, 清水昭彦
Journal: Circulation (2007)
Impact of FLT3-ITD Mutations in Patients with Normal Karyotype Acute Myeloid Leukemia Undergoing Allogeneic Stem Cell Transplantation
Authors: Giovanni Grillo, Elisa Zucchetti, Elena Inzoli, Valentina Mancini, Barbara Forno, Ivana Lotesoriere, Giambattista Bertani, Roberto Cairoli
Journal: Blood (2017)
Methylthioadenosine Phosphorylase (MTAP) deletion is more common in Sarcomatoid (srcRCC) than in clear cell Renal Cell Carcinoma (ccRCC)
Authors: A. Necchi, P. Grivas, P. Spiess, J. Jacob, A. Schrock, R. Madison, D. Pavlick, E. Sokol, N. Danziger, S. Ramkissoon, E. Severson, R. Huang, D. Lin, D. Mata, B. Decker, O. Gjoerup, K. Mcgregor, J. Venstrom, B. Alexander, J. Ross, G. Bratslavsky
Journal: European Urology (2021)
Cutaneous reactions after SARS-CoV-2 vaccination: a cross-sectional Spanish nationwide study of 405 cases
Authors: A. Català, C. Muñoz-Santos, C. Galván-Casas, M. Roncero Riesco, D. Revilla Nebreda, A. Solá-Truyols, P. Giavedoni, M. Llamas-Velasco, C. González-Cruz, X. Cubiró, R. Ruíz-Villaverde, S. Gómez-Armayones, M.P. Gil Mateo, D. Pesqué, O. Marcantonio, D. Fernández-Nieto, J. Romaní, N. Iglesias Pena, L. Carnero Gonzalez, J. Tercedor-Sanchez, G. Carretero, T. Masat-Ticó, P. Rodríguez-Jiménez, A.M. Gimenez-Arnau, M. Utrera-Busquets, E. Vargas Laguna, A.G. Angulo Menéndez, E. San Juan Lasser, M. Iglesias-Sancho, L. Alonso Naranjo, I. Hiltun, E. Cutillas Marco, I. Polimon Olabarrieta, S. Marinero Escobedo, X. García-Navarro, M.J. Calderón Gutiérrez, G. Baeza-Hernández, L. Bou Camps, T. Toledo-Pastrana, A. Guilabert
Journal: British Journal of Dermatology (2021)

Cutaneous reactions after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are poorly characterized.To describe and classify cutaneous reactions after SARS-CoV-2 vaccination.A nationwide Spanish cross-sectional study was conducted. We included patients with cutaneous reactions within 21 days of any dose of the approved vaccines at the time of the study. After a face-to-face visit with a dermatologist, information on cutaneous reactions was collected via an online professional survey and clinical photographs were sent by email. Investigators searched for consensus on clinical patterns and classification.From 16 February to 15 May 2021, we collected 405 reactions after vaccination with the BNT162b2 (Pfizer-BioNTech; 40·2%), mRNA-1273 (Moderna; 36·3%) and AZD1222 (AstraZeneca; 23·5%) vaccines. Mean patient age was 50·7 years and 80·2% were female. Cutaneous reactions were classified as injection site ('COVID arm', 32·1%), urticaria (14·6%), morbilliform (8·9%), papulovesicular (6·4%), pityriasis rosea-like (4·9%) and purpuric (4%) reactions. Varicella zoster and herpes simplex virus reactivations accounted for 13·8% of reactions. The COVID arm was almost exclusive to women (95·4%). The most reported reactions in each vaccine group were COVID arm (mRNA-1273, Moderna, 61·9%), varicella zoster virus reactivation (BNT162b2, Pfizer-BioNTech, 17·2%) and urticaria (AZD1222, AstraZeneca, 21·1%). Most reactions to the mRNA-1273 (Moderna) vaccine were described in women (90·5%). Eighty reactions (21%) were classified as severe/very severe and 81% required treatment.Cutaneous reactions after SARS-CoV-2 vaccination are heterogeneous. Most are mild-to-moderate and self-limiting, although severe/very severe reactions are reported. Knowledge of these reactions during mass vaccination may help healthcare professionals and reassure patients.
In ANCA-associated vasculitis, avacopan was superior to prednisone taper for sustained remission
Authors: Mubeen M. Khan, Donald A. Molony
Journal: Annals of Internal Medicine (2021)

Jayne DRW, Merkel PA, Schall TJ, et al. Avacopan for the treatment of ANCA-associated vasculitis. N Engl J Med. 2021;384:599-609. 33596356.
Detection of lymph node metastases using pooling method by One-Step Nucleic Acid Amplification (OSNA) assay in prostate cancer patients: Preliminary results
Authors: M. Cuadras Sole, J. Planas Morin, A. Celma Domènech, L. Regis Plácido, M.E. Semidey Raven, I.M. De Torres Ramírez, S. Ramón, S. Cajal, B. Congregado Ruiz, C. Baena Villamarín, M.Á. Japón Rodrigues, E. De Álava Casado, D. Marcilla Plaza, L. Martínez-Piñeiro, D. Hardisson, P. González-Peramato, E. García Fernández, O. Buisán Rueda, J. Areal Calama, P.L. Fernández Ruiz, C. Carrato Moñino, M.C. Gómez-Plaza, E. Trilla Herrera, J. Morote Robles
Journal: European Urology (2021)
Distinctive features of severe SARS-CoV-2 pneumonia
Authors: G.R. Scott Budinger, Alexander V. Misharin, Karen M. Ridge, Benjamin D. Singer, Richard G. Wunderink
Journal: Journal of Clinical Investigation (2021)

The coronavirus disease 2019 (COVID-19) pandemic is among the most important public health crises of our generation. Despite the promise of prevention offered by effective vaccines, patients with severe COVID-19 will continue to populate hospitals and intensive care units for the foreseeable future. The most common clinical presentation of severe COVID-19 is hypoxemia and respiratory failure, typical of the acute respiratory distress syndrome (ARDS). Whether the clinical features and pathobiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia differ from those of pneumonia secondary to other pathogens is unclear. This uncertainty has created variability in the application of historically proven therapies for ARDS to patients with COVID-19. We review the available literature and find many similarities between patients with ARDS from pneumonia attributable to SARS-CoV-2 versus other respiratory pathogens. A notable exception is the long duration of illness among patients with COVID-19, which could result from its unique pathobiology. Available data support the use of care pathways and therapies proven effective for patients with ARDS, while pointing to unique features that might be therapeutically targeted for patients with severe SARS-CoV-2 pneumonia.
Secretory Otitis Media: The Cantekin Affair
Authors: Jerome O. Klein
Journal: JAMA (1992)

<h3>To the Editor.</h3> —The recent Editorial<sup>1</sup>about "The Cantekin Affair" by Dr Rennie properly focuses on problems related to peer review and publication. However, by emphasizing the sensational and personal aspects rather than the science of the dispute, the Editorial confuses rather than clarifies the issues about the management of otitis media addressed in the article.<sup>2</sup> Antibiotic treatment of acute bacterial infection in the middle ear is effective therapy that substantially reduces morbidity and sequelae. The fluid that persists after an episode of acute otitis media is known as secretory otitis media or otitis media with effusion and is accompanied by some degree of hearing loss. The use of antibiotics is based on identification of bacterial pathogens in middle-ear fluids of about one third of children with otitis media with effusion and the efficacy of antibiotics is suggested by the data of Mandel et al<sup>3</sup>and others.
Clinical benefit and safety profile of darolutamide in patients who crossed over to darolutamide from placebo during the open-label period of the phase 3 ARAMIS study
Authors: S. Feyerabend, N. Shore, M. Smith, E. Kopyltsov, I. Antonyan, J. Damber, D. Gasparro, A. Yildirim, M. Hellstrom, E. Vjaters, J. Ortiz, S. Srinivasan, T. Sarapohja, K. Fizazi
Journal: European Urology (2021)
Abstract 929: A novel STAT3 inhibitor directly targeting STAT3 N-terminus simultaneously abrogates the nuclear and mitochondrial STAT3 activities leading to highly potent anti-cancer efficacy on the breast cancer
Authors: Jinsuk Kang
Journal: Cancer Research (2021)

Abstract STAT3 functions are largely bifurcated: (1) STAT3 activated by Y705 phosphorylation (pY705) regulates target-gene expression in nucleus. (2) STAT3 activated by S727 phosphorylation (pS727) supports a electron transport complex (ETC) in mitochondria. Constitutive activation of STAT3 has long been considered to correlate with activation of diverse oncogenic pathways, which is a promising target for anti-cancer agents, but clinical therapeutic options are still unsatisfactory. Here we discovered a highly novel small-molecule inhibitor, JW-STAT3i directly binding to STAT3 N-terminal domain: 1) Through the cancer cell line panel screening, JW-STAT3i shows strong anti-cancer potency on various cancer cell lines including the breast cancer cell lines. 2) Anti-cancer mechanism of JW-STAT3i was elucidated: Firstly, the JW-STAT3i impairs pY705-STAT3 to abrogate pro-tumorigenic transcriptional programs mediated by STAT3. Secondly, JW-STAT3i also blocks pS727-STAT3 leading to mitochondrial dysfunction and AMPK activation. Consequently, JW-STAT3i treated cancer cells undergo growth arrest and apoptosis. 3) We further validated JW-STAT3i efficacy using cancer cell line- and patient-derived xenograft models whose response is well-correlated with the predictive biomarkers identified. Accuracy of in vivo efficacy in selected breast cancer PDX models based on predictive biomarker (estimated responders and non-responders) was very high. 4) We also demonstrated that JW-STAT3i shows a strong synergy with anti-PD-L1 antibody by induction of anti-tumorigenic immune environment. In conclusion, JW-STAT3i possesses both negative and positive effects on cancer cell proliferation and anti-immunity respectively. Currently, JW-STAT3i is under preclinical development and highly expected to be a promising anticancer therapeutic option in the near future. Citation Format: Jinsuk Kang. A novel STAT3 inhibitor directly targeting STAT3 N-terminus simultaneously abrogates the nuclear and mitochondrial STAT3 activities leading to highly potent anti-cancer efficacy on the breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 929.