tbuckley/cabot-search huggingface dataset:
Shared Decision Making and the Importance of Time
Authors: Arwen H. Pieterse, Anne M. Stiggelbout, Victor M. Montori
Journal: JAMA (2019)

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Predictors of T Cell Expansion and Clinical Responses Following B-Cell Maturation Antigen-Specific Chimeric Antigen Receptor T Cell Therapy (CART-BCMA) for Relapsed/Refractory Multiple Myeloma (MM)
Authors: Adam D. Cohen, J. Joseph Melenhorst, Alfred L. Garfall, Simon F Lacey, Megan Davis, Dan T. Vogl, Lifeng Tian, Vanessa Gonzalez, Iulian Pruteanu, Anne Marie Nelson, Gabriela Plesa, Adam Waxman, Regina M Young, Bruce L Levine, Carl H June, Edward A. Stadtmauer, Michael C. Milone
Journal: Blood (2018)
TCTAP A-085 Systolic Twist of the Heart in Patients with Dilated Cardiomyopathy vs. Patients Without Heart Failure
Authors: Liliia Zulfatovna Usmanova, Alexander Grigoryevich Osiev, Irina Evgenievna Nikolaeva, Igor V. Buzaev, Lev Khadyevich Yuldybaev
Journal: Journal of the American College of Cardiology (2019)
Adaptation to Plant Communities across the Genome of Arabidopsis thaliana
Authors: Léa Frachon, Baptiste Mayjonade, Claudia Bartoli, Nina-Coralie Hautekèete, Fabrice Roux
Journal: Molecular Biology and Evolution (2019)

Despite the importance of plant-plant interactions on plant community dynamics and crop yield, our understanding of the adaptive genetics underlying these interactions is still limited and deserves to be investigated in the context of complex and diffuse interactions occurring in plant assemblages. Here, based on 145 natural populations of Arabidopsis thaliana located in south-west of France and characterized for plant communities, we conducted a Genome-Environment Association analysis to finely map adaptive genomic regions of A. thaliana associated with plant community descriptors. To control for correlated abiotic environment effects, we also characterized the populations for a set of biologically meaningful climate and soil variables. A nonnegligible fraction of top single nucleotide polymorphisms was associated with both plant community descriptors and abiotic variables, highlighting the importance of considering the actual abiotic drivers of plant communities to disentangle genetic variants for biotic adaptation from genetic variants for abiotic adaptation. The adaptive loci associated with species abundance were highly dependent on the identity of the neighboring species suggesting a high degree of biotic specialization of A. thaliana to members of its plant interaction network. Moreover, the identification of adaptive loci associated with α-diversity and composition of plant communities supports the ability of A. thaliana to interact simultaneously with multiple plant neighbors, which in turn can help to understand the role of community-wide selection. Altogether, our study highlights that dissecting the genetic basis underlying plant-plant interactions at a regional scale while controlling for abiotic confounding factors can help understanding the adaptive mechanisms modulating natural plant assemblages.
Underwater endoscopic mucosal resection for a colonic polyp located at the scar after endoscopic band ligation
Authors: Yoshiyasu Kono, Tetsuya Katayama, Koji Miyahara, Yuki Moritou, Reiji Higashi, Masaki Kunihiro, Masahiro Nakagawa
Journal: Endoscopy (2019)

A man in his 70s was admitted to our hospital for detailed investigation of bloody stool. Emergency colonoscopy showed multiple colonic diverticula, one of which had stigmata of recent hemorrhaging, and endoscopic band ligation (EBL) was performed ([Fig.1 a]) [1].
Sodium-glucose co-transporter-2 inhibitors (SGLT2i) use and risk of amputation: an expert panel overview of the evidence
Authors: Niki Katsiki, George Dimitriadis, George Hahalis, Nikolaos Papanas, Nikolaos Tentolouris, Filippos Triposkiadis, Vasilios Tsimihodimos, Costas Tsioufis, Dimitri P. Mikhailidis, Christos Mantzoros
Journal: Metabolism (2019)
Validation of a novel diagnostic kit using the semi-dry dot-blot method for detecting metastatic lymph nodes in breast cancer.
Authors: Ryota Otsubo, Hiroshi Hirakawa, Masahiro Oikawa, Hiroshi Yano, Hisakazu Shindo, Megumi Matsumoto, Masayuki Baba, Ayako Fukushima, Kenichiro Shibata, Hideki Taniguchi, Takeshi Nagayasu
Journal: Journal of Clinical Oncology (2015)

e22129 Background: The semi-dry dot-blot (SDB) method is a diagnostic procedure for detecting lymph node (LN) metastases. The metastases are visualized by the presence of cytokeratin (CK) with lavage fluid of sectioned LNs by anti-pancytokeratin antibody, based on the theory that epithelial components such as CK are not found in normal LNs. We previously reported 93.3% sensitivity, 96.9% specificity, and 96.6% accuracy for this method in detecting metastasis in sentinel LNs, compared with permanent pathological diagnosis. In this study, we evaluated a novel kit that applies the SDB method using the newly developed anti-CK19 antibody for diagnosing LN metastases in breast cancer. Methods: We obtained 98 LNs dissected from 51 breast cancer patients from July 2013 to September 2014 at our institute. LNs were sliced at 2-mm intervals and washed with phosphate-buffered saline. This lavage fluid was used with the kit to diagnose LN metastasis. The washed LNs were blindly diagnosed by pathologists using hematoxylin and eosin (H&E) stain. Diagnoses based on the kit were compared with their H&E counterparts. Results: Of the 98 LNs, 38 were assessed as positive and 60 as negative by permanent pathological examination with H&E. Use of the kit resulted in correct diagnoses in 30 of the 38 pathologically positive cases and all of pathologically negative cases. Sensitivity, specificity and accuracy of the kit-product in detecting LN metastases were 78.9% (95% confidence interval: 71.7–78.9%), 100% (95.4–100%), and 91.8% (86.2–91.8%), respectively. In 8 false-negative cases, there were 7 micrometastases; therefore, sensitivity was 96.3% (88.4–96.3%) in cases of macrometastases. Diagnosis was achieved in approximately 20 min using the kit, reducing the diagnostic time by half compared with the original SDB method. The cost of this kit was within 8 USD. Conclusions: The kit in our study was accurate, quick, and cost-effective in diagnosing LN metastases. Its sensitivity in detecting macrometastases is excellent, which is important in clinical practice. We are currently developing an improved kit for the detection of smaller metastases.
Do cancer care organizations agree on supportive oncology priorities?
Authors: Christine B. Weldon, Julia Rachel Trosman, Rosa Berardi
Journal: Journal of Clinical Oncology (2015)

e20549 Background: The IOM 2013 cancer report recommends supportive oncology services from diagnosis through survivorship and end of life. We examined what cancer institutions need to implement IOM recommendations in the areas of palliative care, distress management, hospice and survivorship. Funded by the Coleman Foundation. Methods: Study cohort: 35 institutions in a large urban area: 13 cancer treatment sites, 14 cancer support centers, and 8 hospice centers. We conducted interviews of institutional needs to implement IOM recommendations, and a structured survey to determine top 5 priority needs in institutions. Results: Response rate: 100% (35/35 sites). We identified 10 priorities that need to be addressed (Table), with consistent agreement for 7 needs across organization types. Care process for family / caregiver* is a top priority for 0% (0/15) cancer treatment sites, compared to 50% (7/14) support centers and 38% (3/8) hospice (p = 0.006, 0.04). Consolidated, consistent distress and palliative screening tools** was a priority for 54% (7/13) treatment sites, but only 14% (2/14) for support centers and 13% (1/8) for hospice (p = 0.05, 0.09). Conclusions: To support IOM recommendations, participating organizations need to implement stratified supportive oncology processes and utilize providers based on patient needs. Utilizing local collaborations across care sites may facilitate implementation of consistent patient care. Priority % of Cancer Centers % of Support centers % of Hospices Stratified distress process that identifies appropriate provider(s), based on patient needs, site capacity, specialist availability 54 50 50 ** Consolidated, consistent screening tool for distress, palliative and other care needs 54 14 13 Stratified, need based palliative care process 38 14 38 Need-based survivor care process 31 43 0 Institutional leadership buy-in for implementing IOM recommendations 31 14 13 Work with payers to improve supportive oncology reimbursement 23 36 38 Patient education on survivorship 15 36 25 Screening tools and processes to address caregiver needs 15 21 25 Care process for screening at pivotal points of care; clear definitions of pivotal points of care 8 14 13 *Care process for Family / caregivers 0 50 38
High Prevalence of Diabetes in Patients With Primary Aldosteronism (PA) Associated With Subclinical Hypercortisolism and Prediabetes More Prevalent in Bilateral Than Unilateral PA: A Large, Multicenter Cohort Study in Japan
Authors: Yuko Akehi, Toshihiko Yanase, Ryoko Motonaga, Hironobu Umakoshi, Mika Tsuiki, Yoshiyu Takeda, Takashi Yoneda, Isao Kurihara, Hiroshi Itoh, Takuyuki Katabami, Takamasa Ichijo, Norio Wada, Yui Shibayama, Takanobu Yoshimoto, Kenji Ashida, Yoshihiro Ogawa, Junji Kawashima, Masakatsu Sone, Nobuya Inagaki, Katsutoshi Takahashi, Megumi Fujita, Minemori Watanabe, Yuichi Matsuda, Hiroki Kobayashi, Hirotaka Shibata, Kohei Kamemura, Michio Otsuki, Yuichi Fujii, Koichi Yamamoto, Atsushi Ogo, Shintaro Okamura, Shozo Miyauchi, Tomikazu Fukuoka, Shoichiro Izawa, Shigeatsu Hashimoto, Masanobu Yamada, Yuichiro Yoshikawa, Tatsuya Kai, Tomoko Suzuki, Takashi Kawamura, Mitsuhide Naruse
Journal: Diabetes Care (2019)

OBJECTIVE To investigate the prevalence and causes of diabetes in patients with primary aldosteronism (PA) in a multi-institutional cohort study in Japan. RESEARCH DESIGN AND METHODS The prevalence of diabetes was determined in 2,210 patients with PA (diagnosed or glycated hemoglobin [HbA1c] ≥6.5% [≥48 mmol/mol]; NGSP) and compared with that of the Japanese general population according to age and sex. In 1,386 patients with PA and clear laterality (unilateral or bilateral), the effects of plasma aldosterone concentration (PAC), hypokalemia (&amp;lt;3.5 mEq/L), suspected subclinical hypercortisolism (SH; serum cortisol ≥1.8 µg/dL after 1-mg dexamethasone suppression test), and PA laterality on the prevalence of diabetes or prediabetes (5.7% ≤ HbA1c &amp;lt;6.5% [39 mmol/mol ≤ HbA1c &amp;lt;48 mmol/mol]) were examined. RESULTS Of the 2,210 patients with PA, 477 (21.6%) had diabetes. This prevalence is higher than that in the general population (12.1%) or in 10-year cohorts aged 30–69 years. Logistic regression or χ2 test revealed a significant contribution of suspected SH to diabetes. Despite more active PA profiles (e.g., higher PAC and lower potassium concentrations) in unilateral than bilateral PA, BMI and HbA1c values were significantly higher in bilateral PA. PA laterality had no effect on the prevalence of diabetes; however, the prevalence of prediabetes was significantly higher in bilateral than unilateral PA. CONCLUSIONS Individuals with PA have a high prevalence of diabetes, which is associated mainly with SH. The prevalence of prediabetes is greater for bilateral than unilateral PA, suggesting a unique metabolic cause of bilateral PA.
Complete response of renal cell carcinoma vena cava tumor thrombus to neoadjuvant immunotherapy
Authors: Craig Labbate, Ken Hatogai, Ryan Werntz, Walter M. Stadler, Gary D. Steinberg, Scott Eggener, Randy F. Sweis
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Clinically localized renal cell carcinoma is treated primarily with surgery followed by observation or adjuvant sunitinib in selected high-risk patients. The checkpoint inhibitor immunotherapeutic agents nivolumab and ipilimumab have recently shown a survival benefit in the first-line metastatic setting. To date, there have been no reports on the response of localized renal cancer to modern immunotherapy. We report a remarkable response of an advanced tumor thrombus to combined immunotherapy which facilitated curative-intent resection of the non-responding primary renal tumor. We characterized the tumor microenvironment within the responding and non-responding tumors. <h3>Case presentation</h3> A 54-year-old female was diagnosed with a locally advanced clear cell renal cell carcinoma with a level IV tumor thrombus of the vena cava. She was initially deemed unfit for surgical resection due to poor performance status. She underwent neoadjuvant immunotherapy with nivolumab and ipilimumab with a complete response of the vena cava and renal vein tumor thrombus, but had stable disease within her renal mass. She underwent complete surgical resection with negative margins and remains disease-free longer than 1 year after her diagnosis with no further systemic therapy. Notably, pathologic analysis showed a complete response within the vena cava and renal vein, but substantial viable cancer remained in the kidney. Multichannel immunofluorescence was performed and showed marked infiltration of immune cells including CD8<sup>+</sup> T cells and Batf3<sup>+</sup> dendritic cells in the thrombus, while the residual renal tumor showed a non-T cell-inflamed phenotype. <h3>Conclusions</h3> Preoperative immunotherapy with nivolumab and ipilimumab for locally advanced clear cell renal cancer resulted in a complete response of an extensive vena cava tumor thrombus, which enabled curative-intent resection of a non-responding primary tumor. If validated in larger cohorts, preoperative immunotherapy for locally advanced renal cell carcinoma may ultimately impact surgical planning and long-term prognosis.
Emerging roles of allosteric modulators in the regulation of protein‐protein interactions (PPIs): A new paradigm for PPI drug discovery
Authors: Duan Ni, Shaoyong Lu, Jian Zhang
Journal: Medicinal Research Reviews (2019)

Abstract Protein‐protein interactions (PPIs) are closely implicated in various types of cellular activities and are thus pivotal to health and disease states. Given their fundamental roles in a wide range of biological processes, the modulation of PPIs has enormous potential in drug discovery. However, owing to the general properties of large, flat, and featureless interfaces of PPIs, previous attempts have demonstrated that the generation of therapeutic agents targeting PPI interfaces is challenging, rendering them almost “undruggable” for decades. To date, rapid progress in chemical and structural biology techniques has promoted the exploitation of allostery as a novel approach in drug discovery. By attaching to allosteric sites that are topologically and spatially distinct from PPI interfaces, allosteric modulators can achieve improved physiochemical properties. Thus, allosteric modulators may represent an alternative strategy to target intractable PPIs and have attracted intense pharmaceutical interest. In this review, we first briefly introduce the characteristics of PPIs and then present different approaches for investigating PPIs, as well as the latest methods for modulating PPIs. Importantly, we comprehensively review the recent progress in the development of allosteric modulators to inhibit or stabilize PPIs. Finally, we conclude with future perspectives on the discovery of allosteric PPI modulators, especially the application of computational methods to aid in allosteric PPI drug discovery.
Next generation sequencing of synovial sarcomas.
Authors: Myrella Vlenterie, Melissa HS Hillebrandt-Roeffen, Uta E Flucke, Patricia JTA Groenen, Bastiaan BJ Tops, Winette T.A. Van Der Graaf, Yvonne MH Versleijen-Jonkers
Journal: Journal of Clinical Oncology (2015)

10509 Background: Over 95% of synovial sarcoma (SS) share the t(X;18) translocation. Despite this similarity, they show heterogeneous tumor behavior and differ in therapy response. Treatment options are limited and depending on age, 50-90% of patients with localized disease survive 5 year. Therefore we tried to identify targetable mutations in SS. Methods: Mutation sequence analysis including copy number variation was performed on 26 tumors from 22 patients (age 11-78 years), using the comprehensive cancer panel (LifeTechnologies) on the Ion Torrent. We sequenced paired samples from 4 patients: 3 primary tumors with corresponding metastasis and 2 metastases of 1 patient responding divergently to pazopanib. In total, we analyzed 17 primary tumors, 6 metastatic lesions and 3 local relapses. Nonsynonymous variations in coding regions were included. Mutations were filtered for known single nucleotide polymorphisms and earlier found variations in our own research database. The remaining variations were verified by Sanger sequencing and compared to matching normal DNA. All research was performed in agreement with the medical ethical committee. Results: 8 somatic mutations were found in 8 samples. These mutations have not yet been reported in SS. Two are established mutations in oncogenes previously described in carcinomas: KRAS in colon and lung carcinomas and CCND1 in endometrial cancer. Other somatic mutations, with unknown oncogenic character, were found in RNF213, SEPT9, KDR, CSMD3, MLH1 and ERBB4. Similar mutations were found in the paired samples. Chromosomal aberrations, e.g. partial loss of chr 3 or gain of chr 8, were detected in 50% of SS. A loss of chr 6q was seen in the pazopanib resistant lesion and not in the matching lesion responding to pazopanib. Conclusions: To our knowledge this is the largest reported cohort of extensively molecularly analyzed SS. We observed a variety of mutations, the CCND1 mutation being potentially druggable. A possible correlation between 6q loss and pazopanib resistance is subject of ongoing study. The diversity in mutations found underlines the diversity in SS genotypes beyond the known fusion gene. This potentially explains the heterogeneous behavior and emphasizes the challenge in finding new druggable targets in this disease.
PS-039-Role of ductular reaction on the hepatic microenvironment in chronic liver disease
Authors: Silvia Ariño Mons, Beatriz Aguilar-Bravo, Mar Coll, Ester Garcia-Pras, Javier Gallego, Elisa Pose, Delia Blaya, Isabel Graupera, Júlia Vallverdú, Teresa Rubio-Tomás, Juan José Lozano, Joan Caballería, Mercedes Fernández, Pere Ginès, Pau Sancho-Bru
Journal: Journal of Hepatology (2019)
2-Methoxyestradiol (2-ME2, Panzem®) and its new derivatives inhibited lung cancer cells in vitro and in vivo
Authors: Daniel C. F. Chan, Theresa M. Lavallee, Zhiyong Zhang, Limin Zhao, Glenn Swartz, Anthony M. Treston, Paul A. Bunn, William E. Fogler
Journal: Cancer Research (2005)

3415  2-Methoxyestradiol (2ME2, Panzem®) is an endogenous metabolite of estradiol that effectively inhibits a wide range of cancer cell types in vitro, as well as showing antiangiogenic and anti-tumor activities in preclinical models. New analogs of 2ME2 show improved antiproliferative activities and pharmacokinetic parameters as compared to 2ME2 (see P. Burke et al, AACR 2005). In this project, we have used the MTT assay to evaluate the growth inhibitory effects of 2ME2 and three new analogs (883, 900 and 5171) against a panel of human small cell lung cancer cells (SCLC) and non-small cell lung cancer cells (NSCLC). Average IC50 (μM) values are shown in the table below, which range from 0.21 to 1.10 μM for 2ME2; 0.028 to 0.22 μM for 883; 0.058 to 0.43 μM for 900 and 0.46 to 3.05 μM for 5171 respectively. Overall 883 and 900 are significantly more potent than 2ME2 or 5171. There is not much difference in growth inhibitory effects between adenocarcinomas, squamous and large cell lung cancer cells by each of these agents. SCLC cell line proliferation is more effectively inhibited by these four compounds than is NSCLC cell line proliferation. In vivo efficacy of 2ME2 and three analogs was evaluated in athymic nude rats bearing orthotopically implanted H2122 in the left lung. Rats (n=12/group) were treated with saline control or compounds at 10 and 60 mg/kg/day by oral gavage for 50 days. 2ME2 and 900 effectively prolonged survival of rats in a dose-dependent manner, with mean survival for control group at 27 days, 2ME2 10mg/kg at 39 days, 2ME2 60 mg/kg > 50 days, 900 10 mg/kg at 46 days, and 900 60 mg/kg >50 days respectively. Analogs 883 and 5171 at 10 or 60 mg/kg were toxic to the animals. However, this toxicity seemed to be species specific, as separate studies show that mice and dogs tolerate equivalent doses higher than the MTD in rats with no signs of toxicity. Our data suggests that 2ME2 and its analogs have clinical potential for the treatment of human lung cancers.
Early-onset emphysema in a large French-Canadian family: a genetic investigation
Authors: Yohan Bossé, Maxime Lamontagne, Nathalie Gaudreault, Christine Racine, Marie-Hélène Levesque, Benjamin M Smith, Dominique Auger, Alisson Clemenceau, Marie-Ève Paré, Louis Laviolette, Victor Tremblay, Bruno Maranda, Mathieu C Morissette, François Maltais
Journal: The Lancet Respiratory Medicine (2019)