tbuckley/cabot-search huggingface dataset:
Abstract 2774: Establishment of in vitro human T cell exhaustion model to enable high throughput target validation for T cell phenotype restoring
Authors: Tienan Wang, Jie Zhang, Zhijun Wang, Yingnian Li, Linghong Shi, Qing Lin
Journal: Cancer Research (2021)

Abstract Immune surveillance was defined as three phases during tumorigenesis: elimination, equilibrium and escape. During the escape phase, cancer cell acquire a series of mechanism to evade the recognition by immune system, including reduce the function of antigen presenting cells, recruitment of suppressive cells, induce T cell exhaustion etc. The exhaustion phenotype of T cells were frequently observed in various cancer types and exhibit as reduced effector cytokine production, decrease in proliferation and cytolytic activity and overexpression of inhibitory receptors. Restoring T cell exhaustion phenotype become the inspiring filed for cancer therapy and PD1 blocking antibody further encouraging the concept of intervention on T cell exhausted phenotype in tumor microenvironment. In this study, we utilize human primary T cell to establish the in vitro model of T cell exhaustion. Subsequent functional study reveal that the induced exhausted T cell (Tex) display significantly weak response towards dendritic cell activation compare to normal T cell (Tnorm). We take advantage of the model to validate the function of PD1 antibody and demonstrate that blocking of PD1 could partially restore the function of Tex, which suggesting there are still other regulators involved in mediating T cell exhaustion beyond PD1. Citation Format: Tienan Wang, Jie Zhang, Zhijun Wang, Yingnian Li, Linghong Shi, Qing Lin. Establishment of in vitro human T cell exhaustion model to enable high throughput target validation for T cell phenotype restoring [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 2774.
Evaluation of a Point-of-Care Ultrasonography Decision-Support Algorithm for the Diagnosis of Transient Synovitis in the Pediatric Emergency Department
Authors: Marah Zoabi, Noa Kvatinsky, Itai Shavit
Journal: JAMA Network Open (2021)

This case series evaluates the performance of a point-of-care ultrasonography (POCUS) decision-support algorithm for the diagnosis of transient synovitis in the pediatric emergency department (ED).
Overcoming protein-energy malnutrition in older adults in the residential care setting: A narrative review of causes and interventions
Authors: Sophie L. Mathewson, Paula S. Azevedo, Adam L. Gordon, Bethan E. Phillips, Carolyn A. Greig
Journal: Ageing Research Reviews (2021)

Malnutrition, in particular protein-energy malnutrition, is a highly prevalent condition in older adults, and is associated with low muscle mass and function, and increased prevalence of physical frailty. Malnutrition is often exacerbated in the residential care setting due to factors including lack of dentition and appetite, and increased prevalence of dementia and dysphagia. This review aims to provide an overview of the available literature in older adults in the residential care setting regarding the following: links between sarcopenia, frailty, and malnutrition (in particular, protein-energy malnutrition (PEM)), recognition and diagnosis of malnutrition, factors contributing to PEM, and the effectiveness of different forms of protein supplementation (in particular, oral nutritional supplementation (ONS) and protein-fortified foods (PFF)) to target PEM. This review found a lack of consensus on effective malnutrition diagnostic tools and lack of universal requirement for malnutrition screening in the residential care setting, making identifying and treating malnutrition in this population a challenge. When assessing the use of protein supplementation in the residential care setting, the two primary forms of supplementation were ONS and PFF. There is evidence that ONS and PFF increase protein and energy intakes in residential care setting, yet compliance with supplementation and their impact on functional status is unclear and conflicting. Further research comparing the use of ONS and PFF is needed to fully determine feasibility and efficacy of protein supplementation in the residential care setting.
Abstract P049: Cognitive Function and Brain Structure and Risk for Incident Diabetes: The Atherosclerosis Risk in Communities Study
Authors: Michael P Bancks, Alvaro Alonso, Rebecca Gottesman, Thomas Mosley, Elizabeth Selvin, James Pankow
Journal: Circulation (2016)

Introduction: Diabetes is an established risk factor for accelerated brain aging; however recent epidemiological studies suggest individuals with lower levels of cognitive functioning may be at increased risk for developing diabetes. Hypothesis: We hypothesized that lower baseline levels of cognitive function and MRI measures of brain pathology are associated with increased risk of diabetes. Methods: We used data on 11,503 adult men and women with cognitive function assessment (ARIC visit 2, 1990-1992) and 1,383 individuals who completed brain MRI (ARIC visit 3, 1993-1995) and were followed through 2012. Cognitive function was calculated as the average of z-scores from three unique neuropsychological tests. Board-certified radiologists adjudicated severity of sulcal size, ventricular size, and white matter hyperintensity (WMH) from brain MRI to a 10-point visual matching scale. Incident diabetes was ascertained at ARIC visits 3, 4 (1996-1998), and 5 (2010-2012) [self-report of diabetes medication use, self-report of a physician diagnosis, fasting glucose ≥ 126 mg/dL (≥ 7.0 mmol/L) or by non-fasting glucose ≥ 200 mg/dL (≥ 11.1 mmol/L)] and at annual telephone follow-up calls by self-report of physician diagnosis or diabetes medication use. Cox proportional hazards regression analysis was used to estimate hazard ratios (HR) for incident diabetes according to 1 standard deviation (SD) increment of cognitive function and severity of each brain MRI measure. Minimally adjusted models included age, sex, race, and field center. More fully adjusted models included other potentially relevant characteristics and diabetes risk factors. Results: Mean follow-up for the cognitive function analysis was 16.7 years and 14.2 years for the MRI analyses. Summary statistics and hazard estimates are presented in the Table (below). Conclusion: Measures of brain atrophy were associated with an increased incidence of diabetes in more fully adjusted models, but cognitive function and other measures of brain structure were not.
Abstract 3178: A research tool for elucidating the interaction between human mucin 16 (CA125) and immune cells in ovarian cancer
Authors: Kornel Lakatos, Petra Krauledat, German Gonzalez Serrano, Peter Hansen, Daniel William Cramer, Kevin Elias, Manish Patankar, Jawad Hoballah
Journal: Cancer Research (2021)

Abstract CA125 represents the circulating subunit of the large transmembrane glycoprotein MUC 16. Elevated levels of CA125 are suggestive of ovarian cancer and the magnitude of elevation correlates with burden of disease. A rising CA125 level after treatment suggests cancer recurrence. Ovarian tumor cells produce and shed MUC 16 which can bind to certain peripheral immune cells. To study this, current techniques use labelled-fluorescent markers that bind to CA125 on cells and flow cytometry to detect mean fluorescence. A limitation is that this technique may not be able to distinguish low-binding events from autofluorescence. Our new technology improves the resolution for studying CA125 bound to immune cells by employing antibody-labelled gold nanoparticles with far-greater sensitivity than fluorescent markers. The cells are then examined using darkfied microscopy rather than flow, which also permits automated slide scanning and focusing for 3-dimensional counting. This enables both simultaneous use of fluorescent markers to identify the immune cell populations as well as automated image analysis to quantify the amount of bound CA125 on individual cells. Preliminary data show that MUC 16 is preferentially bound to NK and T cells in women with ovarian cancer compared to binding in healthy controls. These insights may help elucidate the function of CA125 in ovarian cancer and improve our understanding of immune-tumor interactions. Citation Format: Kornel Lakatos, Petra Krauledat, German Gonzalez Serrano, Peter Hansen, Daniel William Cramer, Kevin Elias, Manish Patankar, Jawad Hoballah. A research tool for elucidating the interaction between human mucin 16 (CA125) and immune cells in ovarian 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 3178.
Percutaneous ablation versus surgical resection for local recurrence following partial nephrectomy for renal cell cancer: A propensity score analysis (REPART Study – UroCCR 71)
Authors: M. Brassier, Z-E. Khene, J-C. Bernhard, V.T. Dang, I. Ouzaid, F.X. Nouhaud, J. Olivier, C. Nedelcu, N. Grenier, N. Doumerc, K. Bensalah, P. Bigot
Journal: European Urology (2021)
Abstract 2523: Novel genomic characterization in late stage colorectal cancer
Authors: Jianxia Li, Qianchao Wu, Jianwei Zhang, Huabin Hu, Yue Cai, Jiayu Lin, Jun Liu, Yanhong Deng
Journal: Cancer Research (2021)

Abstract Introduction: Colorectal cancer patients with high-level microsatellite instability benefit more from immune checkpoint inhibitor therapy, but they only account for around 15% of all colorectal cancer patients. The remaining patients are still lack of effective therapeutic biomarkers. For patients in late stage without optimal treatment, it is essential to find novel biomarkers which can be used to select appropriate therapies and therefore improve patients' overall survival. Methods: We used whole-exome sequencing to analyze 114 colorectal cancer samples. The samples included 86 primary late stage tumors and 28 metastatic tumors from liver, lung and other organs. The primary samples were further divided into different groups based on their tumor location (sideness) and microsatellite status (MS) since these indications are of great significance in clinical presentation and treatment. We then assessed somatic genomic lesions, copy number variations, germline gene alterations and mutational signatures in the above three pairs of comparisons respectively (primary vs. metastatic, right- vs. left-sided, MS instable vs. stable). Results: There were significant differences between the analyzed pairs. For the primary and metastatic samples, the most prominent difference was the copy number variation which happened in 25 genes in the metastatic samples and only one gene in the primary samples (gain of IL12) (p = 0.036). For the right- and left-sided comparison, SNP/Indel mutations were the most prominent. They happened more frequently in the right-sided than the left-sided tumors and those are rare genes in colorectal cancer, including BCL11A (p = 0.018), DICER1 (p = 0.038), NR4A3 (p = 0.004), NIN (p = 0.008) and FBXW7 (p = 0.019). For the MSI-MSS comparison, tumor mutation burden (TMB) stands out high in the MSI group compared to the MSS group (p &amp;lt; 0.0001). In addition, dozens of significantly mutated genes were observed in the MSI samples (p &amp;lt; 0.0001), such as KMT2B, ACVR2A, KMT2D, ASXL1, TCF7L2 and etc. However, TP53 occurred mainly in the MSS patients (p = 0.0007). Conclusion: Our study enables a deeper understanding of the genomic characterization of colorectal cancer from an integrated view. Copy number variations, gene mutations, and TMB were found to be the most significant differences between the comparison groups of primary vs. metastatic samples, left vs. right sided samples, and MSI vs. MSS samples respectively. Genomic differences between metastatic and primary samples may be potential therapeutic targets for metastatic colorectal cancer. Citation Format: Jianxia Li, Qianchao Wu, Jianwei Zhang, Huabin Hu, Yue Cai, Jiayu Lin, Jun Liu, Yanhong Deng. Novel genomic characterization in late stage colorectal 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 2523.
Abstract 2974: Loss of <i>TSC1</i> or <i>TSC2</i> drives lineage infidelity and hamartoma formation in a renal organoid model of angiomyolipoma
Authors: Adam Pietrobon, Sean P. Delaney, Carole Doré, Julien Yockell-Lelievre, Lisa Julian, William L. Stanford
Journal: Cancer Research (2021)

Abstract Renal angiomyolipomas (R-AMLs) are hamartomatous kidney tumors which stain positively for markers of adipocytic, vascular, smooth muscle, and melanocytic lineages. These lesions possess loss of function mutations in either TSC1 or TSC2, which are canonical negative regulators of mTORC1 signaling. To date, there exists no in vitro or in vivo model which faithfully recapitulates the architectural and molecular complexity of R-AMLs. Considering these lesions can be detected very early in life- even congenitally- we hypothesized they arise as a consequence of aberrant tissue development. To test this hypothesis, we generated TSC1-/- and TSC2-/- mutants in four human pluripotent stem cell (hPSC) backgrounds using CRISPR/Cas9 genome engineering. Wild type hPSCs differentiated into renal organoids express markers of the glomerulus, proximal and distal tubules, in a topology that resembles human nephron patterning. Remarkably, wild type renal organoids downregulate mTORC1 signaling compared to adjacent undifferentiated cells. In contrast, both TSC1-/- and TSC2-/- hPSCs exhibit substantial lineage infidelity upon differentiation, staining positively for adipocytic and melanocytic markers which are absent in matched wild type controls. Additionally, knockout lines formed nodular growths with disorganized architecture, resembling the hamartomatous organization of R-AML lesions. These lesions exhibit hyperactive mTORC1 signaling, consistent with human pathology. Together, these data suggest three primary findings: loss of TSC1/2 drives lineage infidelity; TSC1/2 may be required for architectural organization of the kidney parenchyma; and a developmental approach to R-AML modelling may best recapitulate the human disease. Citation Format: Adam Pietrobon, Sean P. Delaney, Carole Doré, Julien Yockell-Lelievre, Lisa Julian, William L. Stanford. Loss of TSC1 or TSC2 drives lineage infidelity and hamartoma formation in a renal organoid model of angiomyolipoma [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 2974.
Abnormal action potential duration restitution in the right ventricular outflow tract and inducibility of ventricular fibrillation in Brugada syndrome
Authors: M Kofune, Ichiro Watanabe, Sonoko Ashino, Yasuo Okumura, Kimie Ohkubo, Tatsuya Kofune, Kenichi Hashimoto, Atsushi Shindo, Hidezo Sugimura, Toshiko Nakai, Satoshi Saitoh
Journal: Circulation (2006)
Abstract 2053: Molecular characterization of <i>BRCA1</i>c.5339T&amp;gt;C missense mutation in DNA damage response of triple-negative breast cancer cells
Authors: Jeong Dong Lee, Min Hwan Kim, Yeon A Choi, Won-Ji Ryu, Hyun Ju Han, Ae Ran Choi, Tae Yeong Kim, Joo Hyuk Sohn
Journal: Cancer Research (2021)

Abstract Purpose Recent studies re-classified the c.5339T-&amp;gt;C; p.Leu1780Pro (L1780P) BRCA1 missense mutation as “likely pathogenic” in ACMG classification, which shows high prevalence in Korean population. This study aims to reveal the molecular mechanisms and therapeutic relevance of BRCA1 L1780P mutation in DNA damaging response of triple-negative breast cancer (TNBC) cells. Method We established MDA-MB 231 and HCC1937 TNBC cell lines expressing BRCA1 wild-type and BRCA1 L1780P by stable transfection of plasmid DNAs. We performed cell proliferation assays of the TNBC cell lines with treatment of olaparib and carboplatin. We compared the protein and mRNA expression level of RAD51 in BRCA1 wild-type and L1780 transfected TNBC cell lines by western blot and RT-PCR, and BRCA1-mediated DNA damaging responses were evaluated by immunofluorescence staining of RAD51 upon olaparib and carboplatin treatment. The growth inhibitory potential of RAD51 inhibitor, RI-1 was tested in BRCA1 L1780P transfected TNBC cell lines. Results BRCA1 L1780P transfected TNBC cells showed higher migration and invasion capacity, as well as increased sensitivity to olaparib and carboplatin compared to BRCA1 wild-type transfected cells. The induction of RAD51 expression on carboplatin treatment was significantly decreased in BRCA1 L1780P TNBC cells compared with BRCA1 wild-type cells. BRCA1 L1780P transfected TNBC cells showed also showed reduced nuclear RAD51 foci formation on carboplatin and olaparib treatment. The molecular interaction between p-BRCA1 and ATM was decreased by BRCA1 L1780P introduction in TNBC cells, suggesting BRCA1 L1780P mutation disrupts binding of p-BRCA1-ATM. In a cell proliferation assay, BRCA1 L1780P transfected TNBC cells were highly sensitive to RAD51 inhibitor (IC50 = 4.15μM). Conclusion This study shows BRCA1 L1780P mutation causes defects in DNA damage responses of TNBC cells by disrupting molecular interaction between p-BRCA1 and ATM, resulting in RAD51 downregulation. The combinatory inhibition of RAD51 and PARP is a candidate strategy for TNBCs with BRCA1 L1780P mutation. Keywords: Triple-negative Breast Cancer; BRCA1 L1780 Mutation; Homologous Recombination Deficiency; RAD51 Citation Format: Jeong Dong Lee, Min Hwan Kim, Yeon A Choi, Won-Ji Ryu, Hyun Ju Han, Ae Ran Choi, Tae Yeong Kim, Joo Hyuk Sohn. Molecular characterization of BRCA1c.5339T&amp;gt;C missense mutation in DNA damage response of triple-negative breast 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 2053.
A Long-Term Safety and Efficacy Study of Givinostat in Patients with Polycythemia Vera: The First 4 Years of Treatment
Authors: Guido Finazzi, Alessandra Iurlo, Bruno Martino, Giuseppe Carli, Attilio Guarini, Richard Noble, Alessandro M. Vannucchi, Nikolas von Bubnoff, Marianna De Muro, Paolo Di Bartolomeo, Mary Frances McMullin, Vincenzo Martinelli, Antonio Pezzutto, Vittorio Rosti, Giorgina Specchia, Paolo Bettica, Sara Manzoni, Silvia Di Tollo, Alessandro Rambaldi
Journal: Blood (2017)
High-Dose Buprenorphine Induction in the Emergency Department for Treatment of Opioid Use Disorder
Authors: Andrew A. Herring, Aidan A. Vosooghi, Joshua Luftig, Erik S. Anderson, Xiwen Zhao, James Dziura, Kathryn F. Hawk, Ryan P. McCormack, Andrew Saxon, Gail D’Onofrio
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Emergency departments (EDs) sporadically use a high-dose buprenorphine induction strategy for the treatment of opioid use disorder (OUD) in response to the increasing potency of the illicit opioid drug supply and commonly encountered delays in access to follow-up care. <h3>Objective</h3> To examine the safety and tolerability of high-dose (&gt;12 mg) buprenorphine induction for patients with OUD presenting to an ED. <h3>Design, Setting, and Participants</h3> In this case series of ED encounters, data were manually abstracted from electronic health records for all ED patients with OUD treated with buprenorphine at a single, urban, safety-net hospital in Oakland, California, for the calendar year 2018. Data analysis was performed from April 2020 to March 2021. <h3>Interventions</h3> ED physicians and advanced practice practitioners were trained on a high-dose sublingual buprenorphine induction protocol, which was then clinically implemented. <h3>Main Outcomes and Measures</h3> Vital signs; use of supplemental oxygen; the presence of precipitated withdrawal, sedation, and respiratory depression; adverse events; length of stay; and hospitalization during and 24 hours after the ED visit were reported according to total sublingual buprenorphine dose (range, 2 to &gt;28 mg). <h3>Results</h3> Among a total of 391 unique patients (median [interquartile range] age, 36 [29-48] years), representing 579 encounters, 267 (68.3%) were male and 170 were (43.5%) Black. Homelessness (88 patients [22.5%]) and psychiatric disorders (161 patients [41.2%]) were common. A high dose of sublingual buprenorphine (&gt;12 mg) was administered by 54 unique clinicians during 366 (63.2%) encounters, including 138 doses (23.8%) greater than or equal to 28 mg. No cases of respiratory depression or sedation were reported. All 5 (0.8%) cases of precipitated withdrawal had no association with dose; 4 cases occurred after doses of 8 mg of buprenorphine. Three serious adverse events unrelated to buprenorphine were identified. Nausea or vomiting was rare (2%-6% of cases). The median (interquartile range) length of stay was 2.4 (1.6-3.75) hours. <h3>Conclusions and Relevance</h3> These findings suggest that high-dose buprenorphine induction, adopted by multiple clinicians in a single-site urban ED, was safe and well tolerated in patients with untreated OUD. Further prospective investigations conducted in multiple sites would enhance these findings.
The probiotic L. casei Zhang slows the progression of acute and chronic kidney disease
Authors: Han Zhu, Chujin Cao, Zhongcai Wu, Heping Zhang, Zhihong Sun, Meng Wang, Huzi Xu, Zhi Zhao, Yuxi Wang, Guangchang Pei, Qian Yang, Fengming Zhu, Juan Yang, Xuan Deng, Yu Hong, Yinzheng Li, Jie Sun, Fan Zhu, Mengxia Shi, Kun Qian, Ting Ye, Xuezhi Zuo, Fenfei Zhao, Jing Guo, Gang Xu, Ying Yao, Rui Zeng
Journal: Cell Metabolism (2021)