tbuckley/cabot-search huggingface dataset:
Linking single-cell measurements of mass, growth rate, and gene expression
Authors: Robert J. Kimmerling, Sanjay M. Prakadan, Alejandro J. Gupta, Nicholas L. Calistri, Mark M. Stevens, Selim Olcum, Nathan Cermak, Riley S. Drake, Kristine Pelton, Frederik De Smet, Keith L. Ligon, Alex K. Shalek, Scott R. Manalis
Journal: Genome biology (2018)

Mass and growth rate are highly integrative measures of cell physiology not discernable via genomic measurements. Here, we introduce a microfluidic platform enabling direct measurement of single-cell mass and growth rate upstream of highly multiplexed single-cell profiling such as single-cell RNA sequencing. We resolve transcriptional signatures associated with single-cell mass and growth rate in L1210 and FL5.12 cell lines and activated CD8+ T cells. Further, we demonstrate a framework using these linked measurements to characterize biophysical heterogeneity in a patient-derived glioblastoma cell line with and without drug treatment. Our results highlight the value of coupled phenotypic metrics in guiding single-cell genomics.
Erlotinib Versus Gemcitabine Plus Cisplatin as Neoadjuvant Treatment of Stage IIIA-N2 <i>EGFR</i>-Mutant Non–Small-Cell Lung Cancer (EMERGING-CTONG 1103): A Randomized Phase II Study
Authors: Wen-Zhao Zhong, Ke-Neng Chen, Chun Chen, Chun-Dong Gu, Jun Wang, Xue-Ning Yang, Wei-Min Mao, Qun Wang, Gui-Bin Qiao, Ying Cheng, Lin Xu, Chang-Li Wang, Ming-Wei Chen, Xiaozheng Kang, Wanpu Yan, Hong-Hong Yan, Ri-Qiang Liao, Jin-Ji Yang, Xu-Chao Zhang, Qing Zhou, Yi-Long Wu
Journal: Journal of Clinical Oncology (2019)

To assess the benefits of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors as neoadjuvant/adjuvant therapies in locally advanced EGFR mutation-positive non-small-cell lung cancer.This was a multicenter (17 centers in China), open-label, phase II, randomized controlled trial of erlotinib versus gemcitabine plus cisplatin (GC chemotherapy) as neoadjuvant/adjuvant therapy in patients with stage IIIA-N2 non-small-cell lung cancer with EGFR mutations in exon 19 or 21 (EMERGING). Patients received erlotinib 150 mg/d (neoadjuvant therapy, 42 days; adjuvant therapy, up to 12 months) or gemcitabine 1,250 mg/m2 plus cisplatin 75 mg/m2 (neoadjuvant therapy, two cycles; adjuvant therapy, up to two cycles). Assessments were performed at 6 weeks and every 3 months postsurgery. The primary end point was objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1; secondary end points were pathologic complete response, progression-free survival (PFS), overall survival, safety, and tolerability.Of 386 patients screened, 72 were randomly assigned to treatment (intention-to-treat population), and 71 were included in the safety analysis (one patient withdrew before treatment). The ORR for neoadjuvant erlotinib versus GC chemotherapy was 54.1% versus 34.3% (odds ratio, 2.26; 95% CI, 0.87 to 5.84; P = .092). No pathologic complete response was identified in either arm. Three (9.7%) of 31 patients and zero of 23 patients in the erlotinib and GC chemotherapy arms, respectively, had a major pathologic response. Median PFS was significantly longer with erlotinib (21.5 months) versus GC chemotherapy (11.4 months; hazard ratio, 0.39; 95% CI, 0.23 to 0.67; P < .001). Observed adverse events reflected those most commonly seen with the two treatments.The primary end point of ORR with 42 days of neoadjuvant erlotinib was not met, but the secondary end point PFS was significantly improved.
Abstract 18898: Fetal Cardiac Intervention for Pulmonary Stenosis or Atresia With Intact Ventricular Septum: A Report From the International Fetal Cardiac Intervention Registry
Authors: Anita J Moon-Grady, Joanna Dangel, Michele Frommelt, Alberto Galindo, Helena Gardiner, Sarah Gelehrter, Sofía Grinenco, Edgar Jaeggi, Simone Pedra, John Simpson
Journal: Circulation (2017)

Introduction: Invasive fetal cardiac intervention (FCI) for relief of right ventricular outflow tract obstruction has been performed with single-institution series reporting technical and physiolog...
Distinct microbes, metabolites, and ecologies define the microbiome in deficient and proficient mismatch repair colorectal cancers
Authors: Vanessa L. Hale, Patricio Jeraldo, Jun Chen, Michael Mundy, Janet Yao, Sambhawa Priya, Gary Keeney, Kelly Lyke, Jason Ridlon, Bryan A. White, Amy J. French, Stephen N. Thibodeau, Christian Diener, Osbaldo Resendis-Antonio, Jaime Gransee, Tumpa Dutta, Xuan-Mai Petterson, Jaeyun Sung, Ran Blekhman, Lisa Boardman, David Larson, Heidi Nelson, Nicholas Chia
Journal: Genome Medicine (2018)

Links between colorectal cancer (CRC) and the gut microbiome have been established, but the specific microbial species and their role in carcinogenesis remain an active area of inquiry. Our understanding would be enhanced by better accounting for tumor subtype, microbial community interactions, metabolism, and ecology.
PF179 DIFFERENT IMPACT OF BCR BREAKPOINT ON THE OUTCOME OF ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION FROM DIFFERENT GRAFT SOURCE FOR PH+ALL IN THE ERA OF TKI
Authors: S. Nishiwaki, S. Mizuta, K. Ohashi, T. Fukuda, N. Uchida, H. Kanamori, M. Onizuka, Y. Ozawa, J. Tanaka, T. Ichinohe, Y. Atsuta, S. Kako
Journal: HemaSphere (2019)

Background: Prognostic significance of different BCR breakpoints in Philadelphia chromosome‐positive acute lymphoblastic leukemia (Ph+ALL) has not been established. BCR‐ABL1 –positive cells outside the B‐lineage compartment was reported in 40% of adult patients with Ph+ALL and the frequency was different between patients with minor BCR (mi‐bcr) and those with Major BCR (Ma‐bcr). This could suggest the possibility of biological differences in Ph+ALL according to BCR breakpoint. In the era of tyrosine kinase inhibitors (TKIs), allogeneic hematopoietic cell transplantation (allo‐HCT) is still considered to be a choice to cure Ph+ALL. Different effect of unrelated graft source was reported on the outcome of allo‐HCT with positive minimal residual disease (MRD) in a recent study. Aims: We aimed to clarify the impact of BCR breakpoint as well as MRD status and graft source on the outcome of allo‐HCT for Ph+ALL in the era of TKI. Methods: We analyzed data from a registry database for 803 adult Ph+ALL patients who underwent unrelated allo‐HCT in the first complete remission. BCR breakpoint was mi‐bcr in 627 patients (78%), and Ma‐bcr in 154 (19%). Results: Overall survival (OS) rates at 4 years were 64% in mi‐bcr and 61% in Ma‐bcr among patients who underwent unrelated bone marrow or peripheral blood transplantation (UBMT) ( P = 0.43), and 65% in mi‐bcr and 67% in Ma‐bcr among patients who underwent unrelated cord blood transplantation (UCBT) ( P = 0.53). Similarly, the cumulative incidence of relapse or non‐relapse mortality (NRM) was not significantly different between patients with mi‐bcr and those with Ma‐bcr in either UBMT or UCBT (Relapse: UBMT, 20% in mi‐bcr and 18% in Ma‐bcr at 4 years, P = 0.73; UCBT, 20% in mi‐bcr and 15% in Ma‐bcr at 4 years, P = 0.35; NRM: UBMT, 25% in mi‐bcr and 30% in Ma‐bcr at 4 years, P = 0.31; UCBT, 23% in mi‐bcr and 26% in Ma‐bcr at 4 years, P = 0.98). BCR breakpoint was not a significant prognostic factor in multivariate analyses, regardless of graft source. However, in subanalyses, Ma‐bcr was a significant risk factor for survival and NRM in multivariate analyses among patients with MRD(+) at UBMT [Ma‐bcr (vs. mi‐bcr): OS: Hazard ratio (HR) 2.29, 95%CI 1.38 to 3.80, P = 0.001; NRM: HR 3.29, 95%CI 1.72 to 6.27, P &lt; 0.001]. NRM was higher in patients with Ma‐bcr than in those with mi‐bcr among patients with MRD(+) at UBMT (44 % in Ma‐bcr vs. 14% in mi‐bcr at 4 years, P &lt; 0.001), which led to lower survival rate in patients with Ma‐bcr. Summary/Conclusion: BCR breakpoint was a significant prognostic factor in Ph+ALL patients with MRD(+) at UBMT. This is the first study reporting the possibility of significant impact of BCR breakpoint on MRD‐based transplant outcome in Ph+ALL in the era of TKI.
Tumor Evolution of Glioma-Intrinsic Gene Expression Subtypes Associates with Immunological Changes in the Microenvironment
Authors: Qianghu Wang, Baoli Hu, Xin Hu, Hoon Kim, Massimo Squatrito, Lisa Scarpace, Ana C. deCarvalho, Sali Lyu, Pengping Li, Yan Li, Floris Barthel, Hee Jin Cho, Yu-Hsi Lin, Nikunj Satani, Emmanuel Martinez-Ledesma, Siyuan Zheng, Edward Chang, Charles-Etienne Gabriel Sauvé, Adriana Olar, Zheng D. Lan, Gaetano Finocchiaro, Joanna J. Phillips, Mitchel S. Berger, Konrad R. Gabrusiewicz, Guocan Wang, Eskil Eskilsson, Jian Hu, Tom Mikkelsen, Ronald A. DePinho, Florian Muller, Amy B. Heimberger, Erik P. Sulman, Do-Hyun Nam, Roel G.W. Verhaak
Journal: Cancer Cell (2017)
Validation of NoSAS (Neck, Obesity, Snoring, Age, Sex) score as a screening tool for obstructive sleep apnea: Analysis in a sleep clinic
Authors: J. Coutinho Costa, A. Rebelo-Marques, J.N. Machado, J.M.R. Gama, C. Santos, F. Teixeira, J. Moita
Journal: Pulmonology (2019)

Screening methods have become increasingly important due to the growing number of patients suspected of having obstructive sleep apnea (OSA) being referred to sleep clinics. The Lausanne NoSAS (Neck circumference, Obesity, Snoring, Age, Sex) score test is a simple, efficient, and easily employed tool enabling identification of individuals at risk for the disease. The score ranges from 0 to 17 and the patient has a high probability of OSA if they have a NoSAS score of 8 or higher.To evaluate the performance of the NoSAS score as a screening tool for the diagnosis of OSA in a sleep clinic.Prospectively, for 12 months, we included all the patients referred by primary care physicians to our sleep unit for clinical evaluation who had undergone in-lab polysomnography (PSG) and completed the NoSAS score. This test assigns 4 points for a neck circumference of more than 40cm, 3 points for a body-mass index of 25kg/m2 to less than 30kg/m2 or 5 points for having a body-mass index of 30kg/m2 or more, 2 points for snoring, 4 points for being older than 55 years of age and 2 points for being male.Of the 294 patients, 70.7% were male, aged 53.5±12.1 years, with a neck circumference of 41.0±3.6cm and a BMI of 30.8±5.1kg/m2. OSA was present in 84.0% of the patients, 34.8% with moderate OSA and 36.4% severe OSA. Using the NoSAS model for the prediction of all OSA, moderate/severe OSA and severe OSA, the area under the ROC (Receiver Operating Characteristic) was 0.770 (IC95%: (0.703; 0.837), p<0.001), 0.746 (IC95%: (0.691; 0.802), p<0.001) and 0.686 (IC95%: (0.622; 0.749), p<0.001), respectively, thus confirming the diagnostic ability of the NoSAS model. With a NoSAS score ≥7, the sensitivity and positive predictive value (PPV) were 94.3% and 87.6% for all OSA, 94.9% and 62.8% for moderate/severe OSA and 100% and 33.8% for severe OSA, respectively. With the same cut-off, the negative predictive value (NPV) for moderate/severe and severe OSA were 67.9% and 100%, respectively. Each increase in the NoSAS score was associated with an increase in the probability of OSA, reaching a 97% OSA probability for a score of 17.The NoSAS score showed high sensitivity and PPV for OSA with specificity and diagnostic accuracy steadily increasing with higher scores. Furthermore, a low score showed high predictive value for the exclusion of moderate/severe OSA. Overall, our results suggest that, in primary care, this score can be a powerful tool for stratifying and prioritizing patients in the diagnosis of OSA. Nevertheless, more studies are needed to evaluate the efficacy of this score in hospital health care, in younger populations, with a predominance of female and non-obese individuals or in cardiovascular disease.
THU0338 SIMVASTATIN-CONJUGATED NANOPARTICLE ENHANCES THE THERAPEUTIC EFFECT OF ADIPOSE-DERIVED STEM CELLS ON INTERSTITIAL LUNG DISEASE
Authors: Takuya Kotani, Takayasu Suzuka, Shogo Matsuda, Masaaki Ii, Tohru Takeuchi, Shigeki Arawaka
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Interstitial lung disease (ILD) associated with connective tissue disease is a life-threatening pathological condition that causes respiratory failure when it progresses. Lung inflammation is treated with corticosteroids and immunosuppressants, and pulmonary fibrosis is treated with anti-fibrosis agents such as pirfenidone and nintedanib. However, many cases are treatment-resistant and the outcome is poor. Moreover, adverse effects such as infections resulting from immunosuppressive therapy are problematic. The development of new treatments is thus required for ILD from the viewpoint of the poor effect and adverse effects of the currently available treatments. Research and development with adipose-derived stem cells (AdSCs) in immunosuppressive therapy have progressed for autoimmune diseases, and favorable outcomes have been reported. In recent years, the effectiveness of AdSCs in ILD model mice has been demonstrated (ref). The statin preparation has not only an angiogenesis promoting action, an immunosuppressive action, an anti-fibrotic action but also an action of promoting a cellular function including a migratory ability. <h3>Objectives:</h3> We have investigated the hypothesis that statin, an agent with pleiotropic effects, could augment the therapeutic potential of AdSCs. <h3>Methods:</h3> ILD was induced by bleomycin (BLM) in C57BL/6 mouse, and the mice were assigned in the following groups: 1) Control, 2) NP-AdSCs (2.5×10<sup>4</sup> cells), and 3) STNP-AdSCs (2.5×10<sup>4</sup> cells). <h3>Results:</h3> Simvastatin-conjugated nanoparticles (STNP) significantly promoted the migration activity and cell survival without changing the proliferation activity, and up-regulated transforming growth factor (TGF) -β1 in vitro assays. Lung inflammation and fibrosis assessed were significantly supressed at 4 weeks after starting BLM administration in STNP-AdSCs group (Figure). The levels of IL-4, IFN-gamma, TNF-alpha, COL1A1, and TIMP1 mRNA expression at 28 days after BLM administration were significantly lower in STNP-AdSCs group compared with that in other groups. <h3>Conclusion:</h3> Simvastatin-conjugated nanoparticles enhanced the therapeutic effect of a small number of AdSCs transplantation. <h3>Reference:</h3> [1] Sci Rep 6; 7 (1): 14608, 2017. <h3>Acknowledgement:</h3> This study was supported by Grants-in-Aid for Scientific Research-KAKENHI- of Japan (18K08160). <h3>Disclosure of Interests:</h3> None declared
Unsupervised Discovery of Demixed, Low-Dimensional Neural Dynamics across Multiple Timescales through Tensor Component Analysis
Authors: Alex H. Williams, Tony Hyun Kim, Forea Wang, Saurabh Vyas, Stephen I. Ryu, Krishna V. Shenoy, Mark Schnitzer, Tamara G. Kolda, Surya Ganguli
Journal: Neuron (2018)
PB1695 ACCURATE DETECTION OF PATHOGENIC FUSION TRANSCRIPTS IN HEMATOLOGICAL MALIGNANCIES USING RNA‐SEQ AND STAR‐FUSION
Authors: J.H. Lee, H.J. Lim, S.J. Kee, S.H. Kim, J.H. Shin, D.H. Yang, H.J. Kim, M.G. Shin
Journal: HemaSphere (2019)

Background: As driver gene fusions that cause hematological malignancy continues to be discovered, appropriate detection methods are needed to diagnose it. Although the conventional multiplex RT‐PCR method showed high sensitivity and specificity, there was a limitation in detecting various newly discovered fusion transcripts. Recently, the next‐generation sequencing (NGS) method introduced into clinical laboratories has been successfully applied to DNA sequencing, while RNA sequencing (RNA‐Seq) have not yet been widely used. This is because of the concerns about sensitivity and specificity, although RNA‐Seq based test have the advantage of being able to detect various novel fusion transcripts. Aims: The aim of this study was to develop an optimized fusion transcript detection method that can accurately detect clinically important pathogenic gene fusions and minimize false positive results by analyzing RNA‐Seq results in various hematological malignancies. Methods: RNA‐Seq was performed in 11 patients with hematologic malignancies (4 AML, 2 APL, 2 ALL, and 3 CML) diagnosed at Chonnam National University Hwasun Hospital, using RNA samples extracted from bone marrow aspirates at the diagnosis. Library were prepared with 1 ug of total RNA for each sample by TruSeq mRNA Sample Prep kit (Illumina, San Diego, USA). Indexed libraries were sequenced using HiSeq2500 platform (Illumina). The data obtained from the sequencing was analyzed using STAR‐Fusion (v1.2.0) and the final pathogenic fusion transcripts were selected by applying the filtering algorithm developed in this study. Results: A total of 12594 fusion transcripts were detected from RNA‐Seq results in 11 subjects, which was 1144.9 per patient. An average of 1.8 final pathogenic fusion transcripts were detected per sample using the optimized filtering algorithm from step 1 to step 4 (fig. 1). The results were consistent with those of conventional multiplex RT‐PCR. The analytical performances of the RNA‐Seq assay for pathogenic fusion detection were a sensitivity of 100% and a specificity of 99.98%. Though the clinical significance was not clear, the presence of five novel fusion transcripts has been demonstrated by direct sequencing. Summary/Conclusion: By applying the filtering algorithm developed in this study, it was possible to find all the pathogenic fusion transcripts with the sensitivity and specificity comparable to the conventional multiplex RT‐PCR method. Using RNA‐Seq, it is possible to identify the exact nucleotide sequence of the fusion transcript and to predict the amino acid sequence of the fusion protein. Therefore RNA‐Seq can be used to establish accurate targets for diagnosis, treatment, and prognosis, and this will open new horizons for future diagnosis and treatment of hematologic malignancies. image
An unstable lump in the groin
Authors: Zain Sheikh, Augustine Akali
Journal: BMJ (2019)

A 49 year old man with type 2 diabetes presented with a three day history of severe right sided groin swelling and pain, feeling generally unwell, fatigue, and fever. His medical history included two myocardial infarctions (11 and 16 years earlier) and a previous right sided inguinal abscess (two years earlier) that healed after incision and drainage. A 20×10 cm lump and skin crepitations were felt in the right groin. Overlying skin appeared healthy with no evidence of erythema, necrosis, or pallor. Glasgow coma scale (GCS) was 15, blood pressure 85/64 mm Hg, heart rate 114 beats/min, temperature 38.4°C, oxygen saturations 98% on room air, and respiratory rate 28 breaths …
THU0609 ULTRASOUND AS A USEFUL TOOL IN THE DIAGNOSIS OF RHEUMATOID ARTHRITIS IN PATIENTS WITH UNDIFFERENTIATED ARTHRITIS
Authors: Marwin Gutierrez, Chiara Bertolazzi, Edwin Castillo, Denise Clavijo Cornejo, Luis Carlos Rodriguez Delgado, Jaime Mendoza Torres, Carlos Pineda, Pedro Santos-Moreno
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Nowadays, rheumatologists face challenges in finding an effective method to classify and treat patients with undifferentiated arthritis (UA). There is a need for new tools that could ensure accurate characterization of inflammatory processes in these patients. <h3>Objectives:</h3> To investigate if a characterization of UA patients using US may help to fulfill the 2010 ACR/EULAR RA classification criteria in a real-life cohort. <h3>Methods:</h3> We conducted a cross sectional study in two rheumatology care clinics. Patients not fulfilling the 2010 ACR/EULAR RA criteria were included. On the examination day, all patients underwent a physical examination, radiographs and US. The 7-joint US score (US 7) was adopted to scan all patients. US was performed according to EULAR criteria and interpreted by OMERACT definitions. Greyscale and power Doppler synovitis and tenosynovitis were scored. Bone erosions were also evaluated during the US examination. <h3>Results:</h3> A total of 204 patients were included. The diagnosis was modified from UA to RA in 86 (42.1%) patients. The greater proportion of synovitis detected by US was the main parameter that allowed changing the diagnosis from UA to RA, and modified the final score of the 2010 ACR/EULAR classification criteria, from a mean (±SD) of 4.6 (0.5), by clinical examination, to 6.5 (0.6) by US. The changes in the score of the 2010 ACR/EULAR classification criteria were from score 4 to score 6 in 6 (7%) patients; from 4 to 7 in 24 (27.9%) patients; from 5 to 6 in 42 (48.8%) patients; from 5 to 7 in 5 (5.8%) patients and from 5 to 8 in 5 (5.8%) patients. In addition to synovitis, a wide range of tenosynovitis and bone erosions were detected by US. Synovitis was more frequently detected in 2<sup>nd</sup>MCPj followed by 2<sup>nd</sup>MTPj and 5<sup>th</sup>MTPj. The tendons of the wrist, 2<sup>nd</sup> and 3<sup>th</sup> finger were the most affected. In relation to bone erosions, 2<sup>nd</sup>MCPj and 5<sup>th</sup>MTPj where the joints with more proportion of anatomical damage. <h3>Conclusion:</h3> US demonstrated to be useful to help accurately classify as RA, patients previously diagnosed with UA. <h3>Disclosure of Interests:</h3> Marwin Gutierrez: None declared, Chiara Bertolazzi: None declared, Edwin Castillo: None declared, Denise Clavijo Cornejo: None declared, Luis Carlos Rodriguez Delgado: None declared, Jaime Mendoza Torres: None declared, Carlos Pineda: None declared, Pedro Santos-Moreno Grant/research support from: Dr Santos has received research grants from Janssen, Abbvie and UCB, Speakers bureau: Dr Santos has received speaker fees from Sanofi, Lilly, Bristol, Pfizer, Abbvie, Janssen and UCB