tbuckley/cabot-search huggingface dataset:
Chronic small intestinal dysmotility presenting as jejunal diverticulosis with refractory malabsorption: role for partial enterectomy?
Authors: Lucas Wauters, Mathias Clarysse, Ina Jochmans, Diethard Monbaliu, Laurens J Ceulemans, Astrid Verbiest, Marc Miserez, Nathalie Lauwers, Wendy Nys, Nelle Pauwels, Martin Hiele, Jacques Pirenne, Tim Vanuytsel
Journal: Gut (2021)

We read with interest the guidelines on the management of adult patients with severe chronic small intestinal dysmotility by Nightingale et al .1 Enteric myopathies can indeed manifest as jejunal diverticulosis, either acquired or congenital.2 Besides asymptomatic or acute complicated cases, chronic malabsorption due to bacterial overgrowth is a possible presentation of jejunal diverticulosis.3 As stated in the guidelines, this mechanism may lead to malnutrition or even intestinal failure.1 Although surgical options (resection, bypass or stoma formation) were discussed for pseudo-obstruction, resection of diverticula is usually not considered, as surgical outcomes of treatment-refractory cases have been rarely reported.

We report here on our experience with a small series of patients with documented and refractory malabsorption due to small bowel diverticulosis who underwent partial enterectomy at the Leuven Intestinal Failure and Transplantation Centre (Leuven, Belgium) after consent. Bacterial overgrowth, steatorrhoea and medical treatment, including home parenteral nutrition (PN), were assessed. Median (range) time to referral and surgery, length …
Radiation-induced bystander effects impair transplanted human hematopoietic stem cells via oxidative DNA damage
Authors: Linping Hu, Xiuxiu Yin, Yawen Zhang, Aiming Pang, Xiaowei Xie, Shangda Yang, Caiying Zhu, Yapu Li, Biao Zhang, Yaojin Huang, Yunhong Tian, Mei Wang, Wenbin Cao, Shulian Chen, Yawei Zheng, Shihui Ma, Fang Dong, Sha Hao, Sizhou Feng, Yongxin Ru, Hui Cheng, Erlie Jiang, Tao Cheng
Journal: Blood (2021)
Abstract PO-006: Artificial intelligence aided interpretation of ALK fluorescent in situ hybridization for lung cancer: An algorithm development based on 10-year-annotated quality control files in central laboratory
Authors: Tae-Jung Kim, Ho Chul Kang, Yonggeun Lee, Seokman Seo, Donghwan Kim, Sungjin Cho
Journal: Clinical Cancer Research (2021)

Abstract Molecular testing became the most important part of lung cancer diagnostics. Among them, an interpretation of fluorescent in situ hybridization (FISH) is challenging for the routine clinical samples with various amounts and quality. In this study, we trained a variant of DenseNet, a convolutional neural network model with the highest performance in image classification and suitable for quality assessment. Train dataset is composed of the arbitrarily classified dataset made and assessed by a professional pathologist during routine molecular test using whole-slide tissue images and molecular profiles including DNA density and the signal intensity of FISH obtained from 15,000 tests from lung cancer biopsies and resections, which were sent to the central laboratory for molecular studies from 45 hospitals nationwide. The performance of our platform is tested and compared to the quality assessment dataset made from each a general pathologist and a technician. The performance of our method for classifying DNA concentration and the signal intensity of FISH is comparable to that of a general pathologist and technicians. we are under improving its average area under the curve (AUC) over 0.85. This result suggests that a deep learning model based on a convolutional neural network can assist pathologists and pathology technician in rigorous assessing the quality of tissue morphology and signal of FISH for tissue samples with various molecular quality before or during the molecular test and can be applied to quality control of lung cancer molecular testing in a central laboratory. Citation Format: Tae-Jung Kim, Ho Chul Kang, Yonggeun Lee, Seokman Seo, Donghwan Kim, Sungjin Cho. Artificial intelligence aided interpretation of ALK fluorescent in situ hybridization for lung cancer: An algorithm development based on 10-year-annotated quality control files in central laboratory [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr PO-006.
Overall Survival with Ribociclib plus Fulvestrant in Advanced Breast Cancer
Authors: Dennis J. Slamon, Patrick Neven, Stephen Chia, Peter A. Fasching, Michelino De Laurentiis, Seock-Ah Im, Katarina Petrakova, Giulia V. Bianchi, Francisco J. Esteva, Miguel Martín, Arnd Nusch, Gabe S. Sonke, Luis De la Cruz-Merino, J. Thaddeus Beck, Xavier Pivot, Manu Sondhi, Yingbo Wang, Arunava Chakravartty, Karen Rodriguez-Lorenc, Tetiana Taran, Guy Jerusalem
Journal: New England Journal of Medicine (2019)

In an earlier analysis of this phase 3 trial, ribociclib plus fulvestrant showed a greater benefit with regard to progression-free survival than fulvestrant alone in postmenopausal patients with hormone-receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer. Here we report the results of a protocol-specified second interim analysis of overall survival.
Metformin again? Atheroprotection mediated by macrophage AMPK and ATF1
Authors: Ian P Salt, Julia R C Nunes, Morgan D Fullerton
Journal: Cardiovascular Research (2021)

Metformin is a biguanide that has been used as a frontline treatment for type 2 diabetes (T2DM) over the past 60 years, though its medicinal roots date back to medieval times.While new medications have emerged in recent years, metformin remains the most widely prescribed anti-diabetic drug.Despite this, the molecular
Abstract PO001: Molecular interplay between bone marrow-resident cells (BMRCs) and CTCs in Breast Cancer
Authors: Debasish Boral, Shelby R. Kenney, Haowen N. Liu, Dario Marchetti
Journal: Cancer Research (2021)

Abstract Despite widespread knowledge that bone marrow-resident breast cancer cells (BMRCs) affect tumor progression, signaling mechanisms of BMRCs implicated in maintaining long-term dormancy have not been characterized. Further, there is no model of clinical dormancy that can comprehensively emulate the entire spectrum of heterogeneous clones of Circulating Tumor Cells (CTCs) present in cancer patients. To overcome these hurdles, we developed a new experimental model of clinical dormancy employing patient-isolated de novo CTCs and their injection in xenografts with subsequent tumor monitoring and CTC characterization (ex vivo CTCs). We hypothesized that significant distinctions exist between signaling pathways of bone marrow-homing vs metastasis-competent CTCs upon transplantation in xenografts. Comparative transcriptomic analyses of ex vivo vs de novo CTCs identified increased mTOR signaling – a critical pathway frequently dysregulated in breast cancer and implicated in cell survival and dormancy – with contrasting actions by its two complementary arms (mTORC2/mTORC1). Heightened mTORC2 downstream targets augmented quiescent CTCs (Ki67-/RBL2+ cells) in paired breast cancer tissues, along with high mTORC2 activity in solitary BMRCs and tissue-resident CTCs. Further, shRNA mediated knockdown of RICTOR, an essential component of mTORC2, augmented Ki67/PCNA biomarker expression and proliferation. Collectively, these findings suggest that the balance between mTORC1 vs mTORC2 signaling regulates CTC-associated mitotic and/or dormancy characteristics. Further elucidation of mTOR-mediated CTC dormancy will provide novel strategies for therapeutic interventions in patients having early-event metastatic seeding but yet to develop clinically-detectable overt metastasis. Citation Format: Debasish Boral, Shelby R. Kenney, Haowen N. Liu, Dario Marchetti. Molecular interplay between bone marrow-resident cells (BMRCs) and CTCs in Breast Cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr PO001.
Abstract IA-07: Radiomics: Transforming standard imaging into mineable data for diagnostic and theragnostic applications
Authors: Philippe Lambin
Journal: Clinical Cancer Research (2021)

Abstract The rise of radiomics, the high-throughput mining of quantitative image features from (standard-of-care) medical imaging for knowledge extraction and application within clinical decision support systems (animation: https://youtu.be/Tq980GEVP0Y) to improve diagnostic, prognostic, and predictive accuracy, has significant and substantial implications for the medical community (1, 2, 5). Radiomic analysis exploits sophisticated image analysis tools and the exponential growth of medical imaging data to develop and validate powerful image-based signatures/models. We will describe the process of radiomics, its pitfalls, challenges, opportunities, and its capacity to improve clinical decision making (presently primarily in the care of patients with cancer, however, all imaged patients may benefit from quantitative radiology) (5,8). Finally, the field of radiomics is emerging rapidly; however, the field lacks standardized evaluation of both the scientific integrity and the clinical significance of the numerous published radiomics investigations resulting from this growth. There is a clear and present need for rigorous evaluation criteria and reporting guidelines in order for radiomics to mature as a discipline (see www.radiomics.world). Certain author’s proposed that radiomics could be used as a “virtual biopsy”. It could be the case in the sense that several reports demonstrated that biological features of tumours such as EGFR mutations, HPV status and even hypoxia could be quantified by radiomics (6). There are however two main differences: a) Radiomics is based on the whole tumour in contrast to a biopsy taken most often randomly in an heterogeneous tumour and b) the radiomics values is a continuous variable in contrast to molecular biology assays which are often dichotomized (e.g. mt vs wt). Interestingly, certain radiomics signatures e.g. a proliferation radiomics signature, works as well with cone beam CT which opens the field of “4D-Radiomics” (4, 7). The next step is however a “totalomisc” approach in which radiomics signatures will be used in a multifactorial Decision Support System for both diagnostic or theragnostic questions (3, 9, 10). Citation Format: Philippe Lambin. Radiomics: Transforming standard imaging into mineable data for diagnostic and theragnostic applications [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr IA-07.
Development of Severe COVID-19 Adaptive Risk Predictor (SCARP), a Calculator to Predict Severe Disease or Death in Hospitalized Patients With COVID-19
Authors: Shannon Wongvibulsin, Brian T. Garibaldi, Annukka A.R. Antar, Jiyang Wen, Mei-Cheng Wang, Amita Gupta, Robert Bollinger, Yanxun Xu, Kunbo Wang, Joshua F. Betz, John Muschelli, Karen Bandeen-Roche, Scott L. Zeger, Matthew L. Robinson
Journal: Annals of Internal Medicine (2021)

Predicting the clinical trajectory of individual patients hospitalized with coronavirus disease 2019 (COVID-19) is challenging but necessary to inform clinical care. The majority of COVID-19 prognostic tools use only data present upon admission and do not incorporate changes occurring after admission.
The impact of hypertension on response rates in patients with renal cell carcinoma.
Authors: Diana Maslov, Karine Tawagi, Madhav KC, Richa Goel, Helen Yuan, Adi Bamnolker, Zoe Blake, William Song, Daniel Johnson, Marc Ryan Matrana
Journal: Journal of Clinical Oncology (2021)

287 Background: There are many clinical trials that demonstrate the benefits of immunotherapies and targeted therapies in patients (pts) with advanced or metastatic RCC (mRCC). Most of these studies specifically exclude many real-world pts with comorbidities such as autoimmune disease, heart failure, and hypertension. Data on treatment efficacy and adverse events in patients with a history of uncontrolled hypertension is lacking, as there have been few studies analyzing more recently approved RCC drug regimens in real-world practice. Methods: We retrospectively collected data from pts with mRCC treated with immunotherapy and/or targeted therapies. Patient characteristics, performance status, treatment type, reason for treatment discontinuation, treatment response/progression per RECIST v1.1, survival, and presence of clinical trial exclusion criteria such as hypertension, heart failure, presence of autoimmune disease, renal or liver failure, and International Metastatic RCC Database Consortium (IMDC) Risk score were collected. Results: A total of 198 pts were included. The majority of patients received Tyrosine Kinase Inhibitors (TKIs) (42.42% pazopanib (n = 84), 21.71% sunitinib (n = 43), 13.64% cabozantinib (n = 27)), whereas 10.61% were on combination of axitinib + pembrolizumab (n = 21) and 11.62% received ipilimumab + nivolumab (n = 23), and. 71.72% of patients who qualified for systemic therapy had a history of uncontrolled hypertension, whereas 28.28 % of total patients had no history of uncontrolled hypertension. The median time on first-line treatment was 5.17 months. A history of hypertension did not significantly affect Overall Survival (OS), 15.90 months median OS for those with hypertension vs 27.80 median OS for those with no hypertension (p = 0.38). Median OS for all patients was 22.80 months. There was also no difference in response rate between those with a history of hypertension vs those with no history of uncontrolled hypertension (p = 0.65) or in Progression Free Survival (PFS) (p = 0.97) Data on how many patients developed exacerbations of hypertension on therapy will be available at time of presentation. Conclusions: Uncontrolled hypertension typically excludes patients from clinical trial enrollment. We found no difference in median OS in those with a history of hypertension compared to those with normal blood pressures. Further large-scale studies are needed to further determine outcomes in patients with hypertension on systemic therapy for mRCC.
Novel molecular subgroups within the context of receptor tyrosine kinase and adhesion signalling in multiple myeloma
Authors: Ellen Leich, Martin Schreder, Jordan Pischimarov, Thorsten Stühmer, Torsten Steinbrunn, Martina Rudelius, Daniela Brünnert, Manik Chatterjee, Christian Langer, Sarah Keppler, Sofia Catalina Heredia-Guerrero, Hermann Einsele, Stefan Knop, Ralf Christian Bargou, Andreas Rosenwald
Journal: Blood Cancer Journal (2021)
Multifunctional bioactive core-shell electrospun membrane capable to terminate inflammatory cycle and promote angiogenesis in diabetic wound
Authors: Atta ur Rehman Khan, Kai Huang, Mina Shahriari Khalaji, Fan Yu, Xianrui Xie, Tonghe Zhu, Yosry Morsi, Zhao Jinzhong, Xiumei Mo
Journal: Bioactive Materials (2021)

Diabetic wound (DW) healing is a major clinical challenge due to multifactorial complications leading to prolonged inflammation. Electrospun nanofibrous (NF) membranes, due to special structural features, are promising biomaterials capable to promote DW healing through the delivery of active agents in a controlled manner. Herein, we report a multifunctional composite NF membrane loaded with ZnO nanoparticles (NP) and oregano essential oil (OEO), employing a new loading strategy, capable to sustainedly co-deliver bioactive agents. Physicochemical characterization revealed the successful fabrication of loaded nanofibers with strong in vitro anti-bacterial and anti-oxidant activities. Furthermore, in vivo wound healing confirmed the potential of bioactive NF membranes in epithelialization and granulation tissue formation. The angiogenesis was greatly prompted by the bioactive NF membranes through expression of vascular endothelial growth factor (VEGF). Moreover, the proposed NF membrane successfully terminated the inflammatory cycle by downregulating the pro-inflammatory cytokines interleukin −6 (IL-6) and matrix metalloproteinases-9 (MMP-9). In vitro and in vivo studies revealed the proposed NF membrane is a promising dressing material for the healing of DW.
Salvage chemotherapy with cisplatin, ifosfamide, and paclitaxel in metastatic castration-resistant prostate cancer.
Authors: Gunhild Von Amsberg, Mirjam Zilles, Philipp Gild, Winfried Alsdorf, Lukas Boeckelmann, Claudia Langebrake, Su Jung Oh-Hohenhorst, Derya Tilki, Markus Graefen, Sergey Dyshlovoy, Carsten Bokemeyer
Journal: Journal of Clinical Oncology (2021)

123 Background: Recent developments in the treatment of metastatic castration resistant prostate cancer (mCRPC) lead to a revival of platinum-based chemotherapy demonstrating increased activity in patients with aggressive variants of disease. Here, we report on the results of a combinational salvage therapy with cisplatin, ifosfamide and paclitaxel (TIP) in mCRPC. Methods: We retrospectively analyzed patients with mCRPC treated with TIP at the University Hospital Hamburg-Eppendorf between November 2013 and September 2020. Accompanying in vitro analyses were performed using human prostate carcinoma cell lines harboring different levels of drug resistance including the docetaxel-resistant sublines PC3-DR and DU45-DR. Results: In total, 17 mCRPC patients treated with TIP were eligible for efficacy analyses with a median age of 65 yrs. At baseline, liver metastases were present in 88%, metastases of other visceral sides (lung, adrenal gland, brain) in 47% and bone metastases in 76% of the patients. Median hemoglobin was 9.8mg/dl, LDH 903 U/l and AP 205 U/l. Median PSA value was 77 ng/ml covering a wide range including three patients with a PSA-value below 1ng/ml. NSE was evaluated in 83% of the patients (median 38,5 U/l). Patients were extensively pretreated with a median of three treatment lines before TIP (100% docetaxel, 82% abirateron and/or enzalutamide, 47% cabazitaxel, 41% others). A median of 3,5 cycles of TIP were applied with 29% of the patients receiving the maximum of 6 cycles. Four patients discontinued treatment due to side effects (PNP, infection, ifosfamide induced psychosis). At interim analyses, 59 % of the patients showed a radiological response or stable disease with only one patient progressing till the end of treatment. Median PFS was 2.5 months, median OS 6 months. A decrease of PSA &gt; 30% and LDH &gt; 50% was observed in 41% and 35% of the patients, respectively. In vitro experiments revealed additive effects of TIP in 22Rv1, LNCaP and DU45 cells and synergistic effects in neuroendocrine LASCPC-01 cells. In PC3 cells, TIP induced antagonistic effects at lower doses, whereas dose-independent additive effects were observed in docetaxel-resistant PC3-DR. Surprisingly, preliminary data of combined therapies with different drug pairs suggest an antagonistic effect of paclitaxel in the combination with both, cisplatin and ifosfamide. Conclusions: Combinational therapy with cisplatin, ifosfamide and paclitaxel showed promising activity in some patients with aggressive mCRPC. Preclinical data suggest that the drug combination of cisplatin and ifosfamide rule the efficacy of TIP in mCRPC.
Safety and Efficacy of Apixaban and Rivaroxaban for the Treatment of Upper Extremity Deep Vein Thrombosis
Authors: Damon E. Houghton, Dalene M. Bott-Kitslaar, Emily Vargas, David O. Hodge, Teresa R. Ransone, Ana Casanegra, Lisa Peterson, Robert D. McBane, Waldemar E. Wysokinski
Journal: Blood (2017)
<i>JAK2</i>-V617F and interferon-α induce megakaryocyte-biased stem cells characterized by decreased long-term functionality
Authors: Tata Nageswara Rao, Nils Hansen, Jan Stetka, Damien Luque Paz, Milena Kalmer, Julian Hilfiker, Max Endele, Nouraiz Ahmed, Lucia Kubovcakova, Margareta Rybarikova, Hui Hao-Shen, Florian Geier, Christian Beisel, Stefan Dirnhofer, Timm Schroeder, Tim H. Brümmendorf, Dominik Wolf, Steffen Koschmieder, Radek C. Skoda
Journal: Blood (2021)
Patient-centric care in bladder cancer: Virtual simulation to benefit clinical decision-making of oncologists.
Authors: Kinjal Parikh, Donna L. Topping, Saee Dhoble, Jacob Cohen, Haleh Kadkhoda, Patrick Kugel, Emily Sherene Van Laar
Journal: Journal of Clinical Oncology (2021)

492 Background: Immunotherapy (IO) utility in bladder cancer (UC) has expanded into multiple stages of disease. Employing IO optimally requires mastery of clinical trial data, patient eligibility criteria, and interpretation of biomarkers and determination of treatment sequencing. Given the nuanced therapeutic decision-making, education was developed in partnership between Medscape Oncology and Society for Immunotherapy of Cancer (SITC) to assist oncologists in improving their performance surrounding the management of patients with advanced UC. Methods: A virtual patient simulation (VPS) continuing medical education (CME)-certified activity depicting 2 advanced UC cases was made available to oncologist members of Medscape. The cases depicted 1) a patient with newly diagnosed metastatic UC with comorbidities and PDL1+ disease and 2) a patient with advanced UC progressing on platinum therapy with no actionable mutations. The VPS platform captures real-life decision making process of oncologists in an EHR-like format supported by an extensive database of diagnostic and treatment possibilities. Learners were able to interact with patients via video, order lab tests, assess patients, make diagnoses, and order treatments matching the scope and depth of actual practice. Tailored clinical guidance (CG) employing up-to-date evidence-based and faculty recommendations was provided after each decision point. Decisions were collected pre- and post-CG and analyzed using McNemar’s test to determine p-values. Data were collected from 4/28/20 to 7/13/20. Results: Analyses from oncologists (n = 51-66) found significant improvement in performance measured pre- to-post CG: Case 1: Ordering appropriate testing to determine patient eligibility for therapy (39% pre; 65% post; p &lt; .001) Prescribing appropriate therapy based on patient- and disease-specific factors (38% pre; 77% post; p &lt; .001) Providing appropriate counseling and follow-up for a patient receiving treatment (65% pre; 80% post; p &lt; .01) Case 2: Ordering appropriate testing to determine patient eligibility for therapy (39% pre; 57% post; p &lt; .01) Prescribing appropriate therapy based on patient- and disease-specific factors (25% pre; 41% post; p &lt; .01) Providing appropriate counseling and follow-up for a patient receiving treatment (71% pre; 82% post; p &lt; .05). Conclusions: This activity demonstrates the value of providing oncologists a simulation platform to practice and master clinical decision-making of the limitless possible diagnostic and therapeutic options in the management of advanced UC. Insights from rationales for each clinical decision point uncover continued gaps for oncologists on guideline recommendations, efficacy outcomes, or molecular implications. They also highlight barriers including limited experience or confidence with IO.
心電図同期プロスペクティブゲーティングを用いた64列CT冠動脈アンギオグラフィーの冠動脈評価性,診断能力,および照射線量:レトロスペクティブゲーティングとの比較
Authors: Sudo Fumi, Maruyama Takao, Takada Masanori, Hasuike Toshiaki, Fujita Koichi, Saitoh Kiyoko, Yoshizumi Toru
Journal: Circulation (2010)
Diastolic Anterior Leaflet Tethering Contributes to Functional Mitral Stenosis after Restrictive Mitral Valve Annuloplasty
Authors: Philippe B. Bertrand, David Verhaert, C.J. Smeets, Frederik Hendrik Verbrugge, Lars Grieten, W. Mullens, Herbert Gutermann, Robert A Dion, Robert A Levine, Pieter M Vandervoort
Journal: Circulation (2014)