tbuckley/cabot-search huggingface dataset:
Amino Acid PET Imaging of the Early Metabolic Response During Tumor-Treating Fields (TTFields) Therapy in Recurrent Glioblastoma
Authors: Edit Bosnyák, Geoffrey R. Barger, Sharon K. Michelhaugh, Natasha L. Robinette, Alit Amit-Yousif, Sandeep Mittal, Csaba Juhász
Journal: Clinical Nuclear Medicine (2017)

Tumor-treating fields (TTFields) therapy is a relatively new treatment approach for malignant gliomas. We evaluated if amino acid PET can detect an objective metabolic response to TTFields therapy in recurrent glioblastomas. PET scanning with alpha[C-11]-methyl-L-tryptophan (AMT) before and 2 to 3 months after the start of TTFields treatment showed an interval decrease of tryptophan uptake in the whole tumor (2 patients) or in a portion of the tumor (1 patient). These data demonstrate that TTFields therapy can induce an early metabolic response in recurrent glioblastoma, and this treatment response can be detected by amino acid PET.
Are Structural Magnetic Resonance Imaging and General Movements Assessment Sufficient for Early, Accurate Diagnosis of Cerebral Palsy?—Reply
Authors: Iona Novak, Catherine Morgan
Journal: JAMA Pediatrics (2017)

In Reply We thank Parikh for his excellent points and deeply appreciate his efforts to refine advanced magnetic resonance imaging (MRI) biomarkers toward multivariable prediction models in high-income contexts.
Thinking outside the thorax for patients difficult to wean from non-invasive ventilation: amyotrophic lateral sclerosis diagnosis and management in a Respiratory Intermediate Care Unit
Authors: A. Dias, I. Faria, A.C. Santos, C. Bárbara
Journal: Pulmonology (2017)

Respiratory and upper airway muscles weakness cause insufficient ventilation, ineffective cough and bulbar dysfunction in Amyotrophic Lateral Sclerosis (ALS). 1 Dyspnea is the first symptom in only 1---3% of cases.Respiratory failure (RF) at the onset requiring mechanical ventilation (MV) is even more unusual. 2,3ulmonology evaluation should occur at the beginning, in parallel with Neurology, in order to detect early signs of respiratory involvement.Unfortunately, in real life this ideal assessment it is not always possible, especially in the hospitalized patient with acute presentation of disease.Non-invasive ventilation (NIV) and pulmonary rehabilitation interventions for clearing airway secretions are recommended, as necessary. 4t our pulmonology department, whenever possible, acute patients are started on NIV at the Respiratory Intermediate Care Unit (RICU) to ensure better monitoring and optimize adaptation to NIV.The authors describe three cases of ALS presenting with RF admitted to the RICU of Hospital Pulido Valente ---Centro Hospitalar Lisboa Norte in the last 10 years.Our aim is to call attention to the need for ''nonrespiratory'' diagnosis, particularly ALS, in patients dependent on ventilatory support.Case 1: 64-year-old male, smoker (60 pack years), uncooperative with cough measure, presented with dyspnea, anorexia, weight loss (body mass index (BMI) 17.3 kg/m 2 ) for 3 months and with no previous history of disease.There was anemia (9.5 g/dL) and elevated inflammatory parameters on blood tests.Thyroid function was normal.Chest X-ray (CXR) showed no consolidation.Arterial blood gases (ABG) showed global RF (GRF) (FiO 2 21%: pH 7.40; pO 2 = 63 mmHg; pCO 2 = 54 mmHg; HCO 3 = 31 mmol/L; SatO 2 = 93%).Respiratory infection was assumed and treated accordingly.Despite initial improvement, GRF worsened, leading to NIV (pCO 2 > 62 mmHg).Echocardiographic evaluation
Морфофункціональний стан слизової оболонки стравоходу у хворих на гастроезофагеальну рефлюксну хворобу залежно від трофологічного статусу пацієнтів
Authors: H.D. Fadieienko, V.Yu. Halchinska, I.E. Kushnir, V.M. Chernova, N.V. Yefimova, A.S Shapkin
Journal: GASTROENTEROLOGY (2020)

Вивчено морфофункціональний стан слизової оболонки (СО) стравоходу у 57 хворих на гастроезофагеальну рефлюксну хворобу (ГЕРХ) із нормальною (індекс маси тіла (ІМТ) — 18,5–24,9 кг/м2) і надмірною (ІМТ понад 25 кг/м2) масою тіла. Проведено гістологічне та морфометричне дослідження СО стравоходу, імуногістохімічний аналіз експресії маркера апоптозу CD95 і маркера запалення циклооксигенази-2 (ЦОГ-2). Для рефлюкс-езофагіту найбільш характерні зміни багатошарового епітелію — гіперкератоз, паракератоз, проліферація базальних клітин і акантоз. При цьому вірогідних відмінностей морфометричних характеристик у хворих із нормальним ІМТ і надмірною масою тіла виявлено не було. Розвиток рефлюкс-езофагіту супроводжувався порушенням проапоптотичної здатності клітин СО стравоходу і підвищенням експресії ЦОГ-2, найбільш вираженим у хворих з високим ІМТ. Виявлені порушення можуть обумовлювати механізми ускладненого перебігу ГЕРХ у цієї категорії хворих.
Centrifugation‐free washing: A novel approach for removing immunoglobulin A from stored red blood cells
Authors: Eszter Vörös, Nathaniel Z. Piety, Briony C. Strachan, Madeleine Lu, Sergey S. Shevkoplyas
Journal: American Journal of Hematology (2017)

Abstract Washed red blood cells (RBCs) are indicated for immunoglobulin A (IgA) deficient recipients. Centrifugation‐based cell processors commonly used by hospital blood banks cannot consistently reduce IgA below the recommended levels, hence double washing is frequently required. Here, we describe a prototype of a simple, portable, disposable system capable of washing stored RBCs without centrifugation, while reducing IgA below 0.05 mg/dL in a single run. Samples from RBC units ( n = 8, leukoreduced, 4‐6 weeks storage duration) were diluted with normal saline to a hematocrit of 10%, and then washed using either the prototype washing system, or via conventional centrifugation. The efficiency of the two washing methods was quantified and compared by measuring several key in vitro quality metrics. The prototype of the washing system was able to process stored RBCs at a rate of 300 mL/hour, producing a suspension of washed RBCs with 43 ± 3% hematocrit and 86 ± 7% cell recovery. Overall, the two washing methods performed similarly for most measured parameters, lowering the concentration of free hemoglobin by &gt;4‐fold and total free protein by &gt;10‐fold. Importantly, the new washing system reduced the IgA level to 0.02 ± 0.01 mg/mL, a concentration 5‐fold lower than that produced by conventional centrifugation. This proof‐of‐concept study showed that centrifugation may be unnecessary for washing stored RBCs. A simple, disposable, centrifugation‐free washing system could be particularly useful in smaller medical facilities and resource limited settings that may lack access to centrifugation‐based cell processors.
Amplification of Oncolytic Vaccinia Virus Widespread Tumor Cell Killing by Sunitinib through Multiple Mechanisms
Authors: Minah Kim, Maximilian Nitschké, Barbara Sennino, Patrizia Murer, Brian J. Schriver, Alexander Bell, Aishwarya Subramanian, Corry E. McDonald, Jiahu Wang, Howard Cha, Marie-Claude Bourgeois-Daigneault, David H. Kirn, John C. Bell, Naomi De Silva, Caroline J. Breitbach, Donald M. McDonald
Journal: Cancer Research (2017)

Oncolytic viruses pose many questions in their use in cancer therapy. In this study, we assessed the potential of mpJX-594 (mouse-prototype JX-594), a replication-competent vaccinia virus administered by intravenous injection, to target the tumor vasculature, produce immune activation and tumor cell killing more widespread than the infection, and suppress invasion and metastasis. These actions were examined in RIP-Tag2 transgenic mice with pancreatic neuroendocrine tumors that developed spontaneously and progressed as in humans. mpJX-594 initially infected tumor vascular endothelial cells, leading to vascular pruning and prolonged leakage in tumors but not in normal organs; parallel effects were observed in U87 gliomas. Viral infection spread to tumor cells, where tumor cell killing was much more widespread than the infection. Widespread tumor cell killing at 5 days was prevented by depletion of CD8+ T lymphocytes and did not require GM-CSF, as mpJX-594 variants that expressed human, mouse, or no GM-CSF produced equivalent amounts of killing. The antivascular, antitumor, and antimetastatic effects of mpJX-594 were amplified by concurrent or sequential administration of sunitinib, a multitargeted receptor tyrosine kinase inhibitor. These effects were not mimicked by selective inhibition of VEGFR2 despite equivalent vascular pruning, but were accompanied by suppression of regulatory T cells and greater influx of activated CD8+ T cells. Together, our results showed that mpJX-594 targets tumor blood vessels, spreads secondarily to tumor cells, and produces widespread CD8+ T-cell-dependent tumor cell killing in primary tumors and metastases, and that these effects can be amplified by coadministration of sunitinib.Significance: These findings reveal multiple unrecognized features of the antitumor properties of oncolytic vaccinia viruses, all of which can be amplified by the multitargeted kinase inhibitor sunitinib. Cancer Res; 78(4); 922-37. ©2017 AACR.
Tumor CDKN2A-Associated JAK2 Loss and Susceptibility to Immunotherapy Resistance
Authors: Susanne Horn, Sonia Leonardelli, Antje Sucker, Dirk Schadendorf, Klaus G Griewank, Annette Paschen
Journal: JNCI Journal of the National Cancer Institute (2017)

Poor clinical responses to checkpoint blockade with anti-CTLA-4 and anti-PD-1 antibodies in melanoma have recently been associated with acquired IFNγ resistance that protects tumor cells from the antiproliferative and pro-apoptotic cytokine activity. IFNγ-resistant melanoma cells very often lack functional expression of the IFNγ signaling pathway gene JAK2 due to gene deletions or inactivating gene mutations. Analyzing melanoma cell lines (n = 46, applying next-generation targeted sequencing and single nucleotide polymorphism arrays) as well as available genomic data sets from The Cancer Genome Atlas (TCGA) tumor tissue samples (cutaneous melanoma n = 367, lung squamous cell carcinoma n = 501, bladder urothelial carcinoma n = 408, breast invasive carcinoma n = 768, colorectal adenocarcinoma n = 257), we demonstrate that the frequent chromosomal losses of the tumor suppressor CDKN2A in melanoma and other tumor entities enhance the susceptibility to IFNγ resistance by concomitant deletion of the JAK2 gene (odds ratio = 223.17, 95% confidence interval = 66.91 to 1487.38, two-sided P = 7.6×10-46). Tumors with JAK2 mutations or homozygous JAK2 deletions demonstrate allelic losses covering both CDKN2A and JAK2. This suggests that patients with tumor chromosomal CDKN2A losses are susceptible to developing immunotherapy resistance and should be screened for JAK2 deficiency prior to and under immune checkpoint blocking therapy.
Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis
Authors: Evelina Tacconelli, Elena Carrara, Alessia Savoldi, Stephan Harbarth, Marc Mendelson, Dominique L Monnet, Céline Pulcini, Gunnar Kahlmeter, Jan Kluytmans, Yehuda Carmeli, Marc Ouellette, Kevin Outterson, Jean Patel, Marco Cavaleri, Edward M Cox, Chris R Houchens, M Lindsay Grayson, Paul Hansen, Nalini Singh, Ursula Theuretzbacher, Nicola Magrini, Aaron Oladipo Aboderin, Seif Salem Al-Abri, Nordiah Awang Jalil, Nur Benzonana, Sanjay Bhattacharya, Adrian John Brink, Francesco Robert Burkert, Otto Cars, Giuseppe Cornaglia, Oliver James Dyar, Alex W Friedrich, Ana C Gales, Sumanth Gandra, Christian Georg Giske, Debra A Goff, Herman Goossens, Thomas Gottlieb, Manuel Guzman Blanco, Waleria Hryniewicz, Deepthi Kattula, Timothy Jinks, Souha S Kanj, Lawrence Kerr, Marie-Paule Kieny, Yang Soo Kim, Roman S Kozlov, Jaime Labarca, Ramanan Laxminarayan, Karin Leder, Leonard Leibovici, Gabriel Levy-Hara, Jasper Littman, Surbhi Malhotra-Kumar, Vikas Manchanda, Lorenzo Moja, Babacar Ndoye, Angelo Pan, David L Paterson, Mical Paul, Haibo Qiu, Pilar Ramon-Pardo, Jesús Rodríguez-Baño, Maurizio Sanguinetti, Sharmila Sengupta, Mike Sharland, Massinissa Si-Mehand, Lynn L Silver, Wonkeung Song, Martin Steinbakk, Jens Thomsen, Guy E Thwaites, Jos WM van der Meer, Nguyen Van Kinh, Silvio Vega, Maria Virginia Villegas, Agnes Wechsler-Fördös, Heiman Frank Louis Wertheim, Evelyn Wesangula, Neil Woodford, Fidan O Yilmaz, Anna Zorzet
Journal: The Lancet Infectious Diseases (2017)
Development of a New Tool for Assessing Health-Related Quality of Life (QoL) in Patients with Hereditary Angioedema (HAE): The United States HAE Association (HAEA)-QoL
Authors: Sandra C. Christiansen, Paula J. Busse, Janette Birmingham, Aleena Banerji, William R. Lumry, Bruce L. Zuraw
Journal: Journal of Allergy and Clinical Immunology (2018)
Reflecting on the Bicentennial of Mary Shelley’s <i>Frankenstein</i>
Authors: Eelco F. M. Wijdicks
Journal: JAMA Neurology (2017)

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mTOR Kinase Inhibitors Enhance Efficacy of TKIs in Preclinical Models of Ph-like B-ALL
Authors: Moran Gotesman, Thanh-Trang T Vo, Sharmila Mallya, Qi Zhang, Ce Shi, Markus Müschen, David M. Weinstock, Charles Mullighan, Sarah K Tasian, Marina Konopleva, David A. Fruman
Journal: Blood (2016)
The aromatase inactivator exemestane (Aromasin®) decreases plasma leptin levels in postmenopausal breast cancer patients
Authors: Jürgen Geisler, Dagfinn Ekse, Per E. Lønning
Journal: Cancer Research (2006)

420  Endocrine therapy using aromatase inhibitors, selective estrogen receptor modifiers (SERMs) and other types of endocrine treatment options is playing a major role in the concept of breast cancer treatment and is currently standard treatment of hormone-sensitive (ER and/or PGR positive) breast cancer, both in the adjuvant and metastatic setting. Recently, the adipocytokine leptin has been shown to induce the functional activation of the estrogen receptor alpha (ER-α) in MCF-7 breast cancer cells and to stimulate aromatase activity by interference with the aromatase promoters II and I.3 in vitro. In addition, plasma leptin levels have been shown to be correlated to overall survival in postmenopausal breast cancer patients. Thus, we tested whether different drugs currently established for endocrine therapy of breast cancer may influence on plasma leptin levels. All patients (n = 89) were postmenopausal and treated for metastatic breast cancer at the Department of Medicine, Section of Oncology at the Haukeland University Hospital, Bergen, Norway. Patients treated with the non-steroidal aromatase inhibitors anastrozole (n = 22) and letrozole (n = 21), as well as the steroidal aromatase inactivators formestane (n = 16) and exemestane (n = 10) were available. These findings were compared to patients treated with tamoxifen (n = 7) or diethylstilbestrol (n = 13). Plasma levels of estrone (E1), estradiol (E2) and estrone sulfate (E1S) were measured with highly sensitive radioimmunoassays while plasma leptin levels as well as androstenedione levels were measured with commercial kits. Treatment with exemestane (25 mg daily) caused a significant decrease of plasma leptin levels by 27% (7% -42.7%, geom. mean with 95% inverals of the mean) following about 3 months of treatment (P = 0.022, Wilcoxon9s matched pair signed rank test). In contrast, all other endocrine treatment modalities did not cause any significant change in plasma leptin levels during the first 3 months of treatment. One possible explanation for this distinct effect of exemestane on plasma leptin may be the weak androgen effects of exemestane and its major metabolite 17-hydro-exemestane. Androgens have been suggested to decrease plasma leptin levels while estrogens are believed to increase leptin levels through transcriptional activation of the LEP gene. Thus, our findings suggest a distinct influence of exemestane on the adipocytokine leptin, suggesting an additional mechanism of action to exemestane beside the well-documented potent effect on aromatization. Our preliminary, albeit significant, findings should be confirmed by a larger number of patients treated with exemestane with a longer follow-up.
O-0025 Personalized Treatment Planning of Stage II and IIIA Colon Cancer Patients using Genomic Classifiers (ColoPrint/ MSI-Print)
Authors: Ramon Salazar, Robert Rosenberg, Jaume Capdevila, Victor Moreno, Ulrich Nitsche, Thomas Bachleitner-Hofmann, Paul Roepman, Roberta Gafa, Giovanni Lanza, Sun Tian, Iris Simon
Journal: Annals of Oncology (2012)
Red cell exchange transfusions lower cerebral blood flow and oxygen extraction fraction in pediatric sickle cell anemia
Authors: Kristin P. Guilliams, Melanie E. Fields, Dustin K. Ragan, Cihat Eldeniz, Michael M. Binkley, Yasheng Chen, Liam S. Comiskey, Allan Doctor, Monica L. Hulbert, Joshua S. Shimony, Katie D. Vo, Robert C. McKinstry, Hongyu An, Jin-Moo Lee, Andria L. Ford
Journal: Blood (2017)
Different proprotein convertases pattern of expression in ovarian tumor progression
Authors: Bassi E. Daniel, Robert Page, Jirong Zhang, Russell Schilder, Godwin Andrew, Litwin Samuel, Andres Klein-Szanto
Journal: Cancer Research (2006)

1845   Proprotein convertases (PCs) is a family of serin proteases that activate many substrates that are crucial for tumor progression. Four of the PCs, furin, PC-7, PACE-4 and PC-5 are ubiquitously expressed. Although they accomplish similar biochemical functions, i.e. proteolytic cleavage at the C-terminal portion of the RXR/KR motif, their different subcellular location as well as subtle substrate preferences suggests that their activities are not redundant. In order to determine if the pattern of expression of each of these proteases differ during ovarian tumor progression, we evaluated the expression of furin, PC-7, PACE-4 and PC-5 in human normal and cancer cell lines and in primary tumors. We found that furin RNA expression, determined by RT-PCR, was predominant in cancer cell lines. In addition, its expression was strictly associated with less than five-year survival. Protein analysis by western blot of cell lysates or immunohistochemistry of tumors indicated that furin expression was higher in cancer cell lines or tissues than in their normal counterparts. Conversely, we observed PC-7 RNA expression mainly in normal cell lines and in tumors from patients surviving for more than five years after diagnosis. As in the case of PC-7, we observed PACE-4 silencing in cancer cell lines and, less pronounced in tumors. PC-5 did not show significant expression in most of the samples analyzed. We conclude that these PCs follow a distinct pattern of expression during ovarian tumor progression. Furthermore, furin is associated with poor prognosis. The differential expression in normal and cancer cells/tissues suggest that the ubiquitously expressed PCs may play different roles in ovarian tumor progression, supporting the hypothesis that the activities of the various PCs are not redundant. This work was supported by NIH grant # R01-CA 75028.
Recent Advances in Extrusion‐Based 3D Printing for Biomedical Applications
Authors: Jesse K. Placone, Adam J. Engler
Journal: Advanced Healthcare Materials (2017)

Abstract Additive manufacturing, or 3D printing, has become significantly more commonplace in tissue engineering over the past decade, as a variety of new printing materials have been developed. In extrusion‐based printing, materials are used for applications that range from cell free printing to cell‐laden bioinks that mimic natural tissues. Beyond single tissue applications, multi‐material extrusion based printing has recently been developed to manufacture scaffolds that mimic tissue interfaces. Despite these advances, some material limitations prevent wider adoption of the extrusion‐based 3D printers currently available. This progress report provides an overview of this commonly used printing strategy, as well as insight into how this technique can be improved. As such, it is hoped that the prospective report guides the inclusion of more rigorous material characterization prior to printing, thereby facilitating cross‐platform utilization and reproducibility.
Distinct Patterns of Early Hematopoietic Reconstitution in Patients Receiving Notch Expanded Non HLA-Matched Off-the-Shelf Cord Blood Derived Hematopoietic Stem and Progenitor Cells
Authors: Jianqiang Li, Allen Jiang, Filippo Milano, Suzan Imren, David Charles Keahi Oliver, Joseph Blake, Colleen Delaney
Journal: Blood (2015)
Association between non-alcoholic fatty liver disease and subclinical coronary atherosclerosis: An observational cohort study
Authors: Seung Bum Lee, Gyung-Min Park, Jong-Young Lee, Byung Uk Lee, Jae Ho Park, Byung Gyu Kim, Seok Won Jung, In Du Jeong, Sung-Jo Bang, Jung Woo Shin, Neung Hwa Park, Dong Hyun Yang, Joon-Won Kang, Tae-Hwan Lim, Hong-Kyu Kim, Jaewon Choe, Han Chu Lee
Journal: Journal of Hepatology (2017)