tbuckley/cabot-search huggingface dataset:
P13.09 Inconsistent effect of temozolomide exposure on cell viability in glioblastoma cell line models - a systematic review
Authors: M M C Bruce, M T C Poon, P M Brennan
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND The alkylating agent temozolomide is part of standard care for patients with glioblastoma. Potential novel therapeutic agents are often first evaluated against temozolomide in glioblastoma cell line models. Despite the importance of this step in compound development, there is no standard concentration or exposure duration of temozolomide in laboratory research, and consistency in the effect of temozolomide on glioblastoma cell lines has not been assessed. This systematic review aimed to summarise the concentration and exposure duration of temozolomide and its effect on cell viability in studies using glioblastoma cell lines. MATERIAL AND METHODS We searched Medline and Embase Jan 1994 - Feb 2021 for studies that used at least one glioblastoma cell line and reported a measure of cell viability associated with temozolomide exposure. Studies were excluded if they used modified cell lines or did not report a cell viability measure associated with temozolomide as monotherapy. One reviewer screened all records and two reviewers assessed potentially eligible studies for inclusion. The main data items included the cell lines used, the concentration and exposure duration to temozolomide, and cell viability measures. We summarised findings using descriptive statistics. RESULTS Of 1,533 potentially eligible studies we included 213 studies reporting 209 different cell lines. The most common cell lines were U87, U251 and T98G, used in 61%, 41%, and 27% of studies, respectively. Twenty-five (12%) studies used patient-derived cell lines. The concentration of temozolomide used ranged from 0 to 8000μM. The temozolomide exposure duration ranged from &amp;lt;24 hours to &amp;gt;96 hours, with 29% studies using 72 hours. The most common cell viability measure was half maximal inhibitory concentration (IC50), which was reported in 183 (86%) studies. The median IC50 in 32 studies using the U87 cell line was 180μM (interquartile range [IQR]: 52–254μM) at 48-hour temozolomide exposure and 202μM (IQR 52–518μM) at 72-hour exposure. The median IC50 in 31 studies using U251 cell line was 84μM (IQR: 34–324μM) at 48-hour exposure and 102μM (IQR: 35–358μM) at 72-hour exposure. CONCLUSION Experimental setup of temozolomide and its effect on cell viability vary widely between studies using similar glioblastoma cell lines. This inconsistency of response to temozolomide questions reproducibility and the translational value of study findings.
Evolutionary Learning-Derived Clinical-Radiomic Models for Predicting Early Recurrence of Hepatocellular Carcinoma after Resection
Authors: I-Cheng Lee, Jo-Yu Huang, Ting-Chun Chen, Chia-Heng Yen, Nai-Chi Chiu, Hsuen-En Hwang, Jia-Guan Huang, Chien-An Liu, Gar-Yang Chau, Rheun-Chuan Lee, Yi-Ping Hung, Yee Chao, Shinn-Ying Ho, Yi-Hsiang Huang
Journal: Liver Cancer (2021)

Current prediction models for early recurrence of hepatocellular carcinoma (HCC) after surgical resection remain unsatisfactory. The aim of this study was to develop evolutionary learning-derived prediction models with interpretability using both clinical and radiomic features to predict early recurrence of HCC after surgical resection.Consecutive 517 HCC patients receiving surgical resection with available contrast-enhanced computed tomography (CECT) images before resection were retrospectively enrolled. Patients were randomly assigned to a training set (n = 362) and a test set (n = 155) in a ratio of 7:3. Tumor segmentation of all CECT images including noncontrast phase, arterial phase, and portal venous phase was manually performed for radiomic feature extraction. A novel evolutionary learning-derived method called genetic algorithm for predicting recurrence after surgery of liver cancer (GARSL) was proposed to design prediction models for early recurrence of HCC within 2 years after surgery.A total of 143 features, including 26 preoperative clinical features, 5 postoperative pathological features, and 112 radiomic features were used to develop GARSL preoperative and postoperative models. The area under the receiver operating characteristic curves (AUCs) for early recurrence of HCC within 2 years were 0.781 and 0.767, respectively, in the training set, and 0.739 and 0.741, respectively, in the test set. The accuracy of GARSL models derived from the evolutionary learning method was significantly better than models derived from other well-known machine learning methods or the early recurrence after surgery for liver tumor (ERASL) preoperative (AUC = 0.687, p < 0.001 vs. GARSL preoperative) and ERASL postoperative (AUC = 0.688, p < 0.001 vs. GARSL postoperative) models using clinical features only.The GARSL models using both clinical and radiomic features significantly improved the accuracy to predict early recurrence of HCC after surgical resection, which was significantly better than other well-known machine learning-derived models and currently available clinical models.
Improving the completion rate of outpatient stool-based colon cancer screening during a global pandemic.
Authors: Ye Aung, Christian Scherer, Andrew Gdowski, Doris Cubas, Alexandra Horton, Nabeel Saghir, Holli Sadler
Journal: Journal of Clinical Oncology (2021)

238 Background: Colon Cancer Screening is an important intervention to reduce the morbidity and mortality of colorectal cancer. In particular, stool based screening tests help to increase the availability of screening especially amidst a global pandemic. However stool based screening is limited by patient return rates of FIT/iFOBT tests. Here at the Austin Outpatient VA we sought to improve the FIT test return rate of patients in our resident clinic by at least 20%. Methods: We did a root cause analysis as to why iFOBT/FIT were not being returned, particularly during the height of the pandemic when most visits were virtual. With help from the VA data core we generated a list of 76 patients during a period from 2/3/2020-7/7/2020 who had not returned an ordered FIT/iFOBT test in &gt;30 days. We called these patients to identify the reasons why they did not return their test. Results: We were able to reach (44/76) patients and discovered that only (12/44) 27.3% of patients contacted had received a FIT test. Of our patients-reached 33/44 of them asked for a new FIT test to be sent to them and ultimately (21/44) patients contacted returned and completed their FIT test successfully with 3 tests being positive and referred to diagnostic colonoscopy. This resulted in an improvement in return rate of ̃47% of all patients ultimately contacted. Conclusions: Through a meeting of stakeholders including nurses and resident physicians we discovered in our EMR, that the order to send out a FIT test does not automatically alert a nurse nor does it automatically mail out or send out a FIT test. We discovered there was not a standardized process in place to facilitate communication between physicians ordering tests and nurses, thus FIT/FOBT tests were not being sent. We are currently working on a process to standardize the FIT test ordering process to improve communication between physicians and nurses. We are developing a better order set that reminds providers to alert and message nurses prior to ordering the FIT/iFOBT test. We are also educating Residents about the FIT/FOBT ordering process. With future PDSA cycles we should be able to improve the robustness and reliability of our outpatient colon cancer screening process through improved inter-professional communication.
Gut dysbiosis, defective autophagy and altered immune responses in neurodegenerative diseases: Tales of a vicious cycle
Authors: Saravana Babu Chidambaram, Musthafa Mohamed Essa, A.G. Rathipriya, Muhammed Bishir, Bipul Ray, Arehally M. Mahalakshmi, A.H. Tousif, Meena K. Sakharkar, Rajpal Singh Kashyap, Robert P. Friedland, Tanya M. Monaghan
Journal: Pharmacology & Therapeutics (2021)
The use of mycophenolate mofetil in the treatment of refractory chronic graft versus host disease
Authors: R. S. Pallotta-Filho, J. A. L. Barbosa, M. C. M. A. Macedo, R. Saboya, R. L. Silva, M. Jamra, Dalton de Alencar Fischer Chamone, Frederico Luiz Dulley
Journal: Blood (1998)
Deprivation of dietary fiber in specific-pathogen-free mice promotes susceptibility to the intestinal mucosal pathogen <i>Citrobacter rodentium</i>
Authors: Mareike Neumann, Alex Steimle, Erica T. Grant, Mathis Wolter, Amy Parrish, Stéphanie Willieme, Dirk Brenner, Eric C. Martens, Mahesh S. Desai
Journal: Gut Microbes (2021)

The change of dietary habits in Western societies, including reduced consumption of fiber, is linked to alterations in gut microbial ecology. Nevertheless, mechanistic connections between diet-induced microbiota changes that affect colonization resistance and enteric pathogen susceptibility are still emerging. We sought to investigate how a diet devoid of soluble plant fibers impacts the structure and function of a conventional gut microbiota in specific-pathogen-free (SPF) mice and how such changes alter susceptibility to a rodent enteric pathogen. We show that absence of dietary fiber intake leads to shifts in the abundances of specific taxa, microbiome-mediated erosion of the colonic mucus barrier, a reduction of intestinal barrier-promoting short-chain fatty acids, and increases in markers of mucosal barrier integrity disruption. Importantly, our results highlight that these low-fiber diet-induced changes in the gut microbial ecology collectively contribute to a lethal colitis by the mucosal pathogen Citrobacter rodentium, which is used as a mouse model for enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC, respectively). Our study indicates that modern, low-fiber Western-style diets might make individuals more prone to infection by enteric pathogens via the disruption of mucosal barrier integrity by diet-driven changes in the gut microbiota, illustrating possible implications for EPEC and EHEC infections.
Abstract 523: Expression, Activation and Function of Integrin α <sub>M</sub> β <sub>2</sub> on Neutrophil-derived Microparticles
Authors: Neil M Woody, Dorota Szpak, Edward F Plow, Elzbieta Pluskota
Journal: Circulation (2007)

The levels of circulating leukocyte-derived microparticles (MPs) are elevated in thrombosis and most cardiovascular diseases, and it has been suggested that MPs are not only markers of disease but also active contributors to pathogenesis via their interaction with various cell types. Such interactions will depend on the presence and activity of molecules expressed on the MP surface. In our study we have considered the presence and activation state of a major adhesion receptor on the surface of leukocytes, integrin α M β 2 (CD11b/18, Mac-1) on MPs derived from human neutrophils (PMN). MPs were obtained from resting or agonist-stimulated PMNs, and the presence of α M β 2 was assessed by FACS. α M β 2 expression was significantly enhanced on MPs derived from stimulated PMN (e.g., resting MPs: MFI = 3.5 ± 0.7 vs PMA-MPs: MFI = 20 ± 4, and fLMP-MPs: MFI = 24 ± 5). PSGL-1 was expressed by MPs but levels were not affected by stimulation. Of note, α M β 2 expressed on MPs obtained from stimulated PMNs was in active conformation as assessed using mAb (CBRM1/5) to activation-dependent epitope of this integrin. Recognition of a protein ligand, fibrinogen, by activated α M β 2 on the MPs was also demonstrable. With evidence of a functionally active integrin, we sought to evaluate its role in mediating MP interaction with platelets. MP binding to isolated, resting platelets was dose and time dependent. However, MPs expressing activated α M β 2 bound to more platelets, and only MPs obtained from stimulated PMNs induced platelet activation as assessed P-selectin expression (resting-MPs: MFI = 25.1 ± 6.5 vs PMA-MPS: MFI = 293 ± 60, n = 4). MP binding and platelet activation were reduced by ~40–50% by function-blocking mAbs to α M β 2 and GPIbα, implicated as a major counter-receptor for α M β 2 . Complete abrogation of these events was achieved by the combination of blocking reagents to both α M β 2 /GPIbα and to PSGL-1/P-selectin. In conclusion, MPs released by stimulated PMNs express activated α M β 2 . This integrin cooperates with PSGL-1 to mediate interaction with and activation of platelets.
Tireless surveillance by exhausted T cells
Authors: Michael L. Dustin
Journal: Journal of Clinical Investigation (2021)

T cell exhaustion is an evocative concept that results in attenuated function in the face of chronic antigen exposure and is critical to avoid immunopathology. However, tumors often exploit this dampened T cell function to escape the antitumor immune response. In this issue of the JCI, You et al. investigated a different aspect of T cell exhaustion in the setting of tumor immunity by characterizing the capacity of T cells for tireless migration. The dynamic nature of normal T cells was first made famous by intravital microscopy studies in explanted tissues. You et al. used a similar imaging strategy with reanimated human tumors, in which exhausted T cells displayed an enhanced capacity for intratumoral motility. These results suggest that exhausted T cells may be able to teach T cell engineers lessons about navigating within the tumor microenvironment.
Effector T cell responses unleashed by regulatory T cell ablation exacerbate oral squamous cell carcinoma
Authors: Jaime L. Chao, Michael Korzinkin, Alex Zhavoronkov, Ivan V. Ozerov, Matthew T. Walker, Kathleen Higgins, Mark W. Lingen, Evgeny Izumchenko, Peter A. Savage
Journal: Cell Reports Medicine (2021)

Immune suppression by CD4+FOXP3+ regulatory T (Treg) cells and tumor infiltration by CD8+ effector T cells represent two major factors impacting response to cancer immunotherapy. Using deconvolution-based transcriptional profiling of human papilloma virus (HPV)-negative oral squamous cell carcinomas (OSCCs) and other solid cancers, we demonstrate that the density of Treg cells does not correlate with that of CD8+ T cells in many tumors, revealing polarized clusters enriched for either CD8+ T cells or CD4+ Treg and conventional T cells. In a mouse model of carcinogen-induced OSCC characterized by CD4+ T cell enrichment, late-stage Treg cell ablation triggers increased densities of both CD4+ and CD8+ effector T cells within oral lesions. Notably, this intervention does not induce tumor regression but instead induces rapid emergence of invasive OSCCs via an effector T cell-dependent process. Thus, induction of a T cell-inflamed phenotype via therapeutic manipulation of Treg cells may trigger unexpected tumor-promoting effects in OSCC.
Exclusion criteria of breast cancer research protocols: A descriptive analysis.
Authors: Clara Wan, Nicole E. Caston, Stacey A. Ingram, Gabrielle Betty Rocque
Journal: Journal of Clinical Oncology (2021)

82 Background: Clinical trials play an important role in advancing cancer treatments. Unfortunately, only about 3% of adults with cancer are enrolled in a clinical trial in the United States due to various barriers to enrollment. This includes restrictive eligibility criteria, which currently have no standard guidelines. The purpose of this study is to evaluate the variability of eligibility criteria. Methods: This descriptive analysis utilized all therapeutic breast protocols offered at the University of Alabama at Birmingham (UAB) between 2004-2020. Exclusion criteria (e.g., laboratory values and comorbidities) were extracted from protocols using OnCore, an online dataset used to manage clinical trials, and ClinicalTrials.gov. Laboratory values or vital signs analyzed included liver function tests, hematologic labs, Eastern Cooperative Oncology Group (ECOG) performance status, and hypertension. Comorbid conditions included congestive heart failure, cardiovascular disease, presence of central nervous system (CNS) metastases, and history of prior cancer. Comorbid conditions were further analyzed by amount of time protocols required participants to be from initial diagnosis or exacerbation-free. Results: There were a total of 102 eligible protocols. Substantial heterogeneity was observed in exclusion criteria across liver/hematologic laboratory values and demographic/comorbidity variables. Among liver laboratory values, most protocols included an upper limit of acceptable for bilirubin (78%): 9% used the institutional upper limit of normal (ULN), 2% used 1.2xULN, 3% used 1.25xULN, 56% used 1.5xULN, 6% used 2xULN, and 2% used 3xULN. Similar variability was observed in protocols that included alanine transaminase and aspartate transaminase. Among hematological labs, 82% of protocols defined a lower limit of acceptable absolute neutrophil count: 1% 500mcL, 11% used 1,000mcL, 4% used 1,200mcL, 1% used 1,250mcL, 64% used 1,500mcL, and 1% used 1,800mcL. Of the comorbid conditions, exclusion criteria varied for congestive heart failure (49%), an acute exacerbation of cardiovascular disease (80%), CNS metastases (59%) and a prior cancer (66%). While most protocols included cardiovascular disease, the allowable timeframe varied between protocols: 4% did not allow an acute exacerbation within the previous 3 months, 32% did not allow within the previous 6 months, 5% did not allow within the previous 12 months, and 38 % did not specify a time frame. Protocols including history of a prior cancer as a criterion similarly had varied definitions based on timeline. Conclusions: Substantial heterogeneity was observed among clinical trial protocols. While exclusion criteria are necessary for patient safety, there is lack of evidence for current parameters. Future research should focus on defining standardized eligibility criteria while allowing for deviation based on drug specificity.
HPV Vaccination Is Safe—You Don’t Have to Whisper It
Authors: Nosayaba Osazuwa-Peters, Rebecca L Rohde, Eric Adjei Boakye
Journal: JAMA Network Open (2021)

Kalyani Sonawane, PhD; Yueh-Yun Lin, MS; Haluk Damgacioglu, PhD; Yenan Zhu, MS; Maria E. Fernandez, PhD; Jane R. Montealegre, PhD; Cecilia Ganduglia Cazaban, MD, DrPH; Ruosha Li, PhD; David R. Lairson, PhD; Ying Lin, PhD; Anna R. Giuliano, PhD; Ashish A. Deshmukh, PhD, MPH
Risks of and From SARS-CoV-2 Infection and COVID-19 in People With Diabetes: A Systematic Review of Reviews
Authors: Jamie Hartmann-Boyce, Karen Rees, James C. Perring, Sven A. Kerneis, Elizabeth M. Morris, Clare Goyder, Afolarin A. Otunla, Olivia E. James, Nandana R. Syam, Samuel Seidu, Kamlesh Khunti
Journal: Diabetes Care (2021)

BACKGROUND This review was commissioned by the World Health Organization and presents a summary of the latest research evidence on the impact of coronavirus disease 2019 (COVID-19) on people with diabetes (PWD). PURPOSE To review the evidence regarding the extent to which PWD are at increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and/or of suffering its complications, including associated mortality. DATA SOURCES We searched the Cochrane COVID-19 Study Register, Embase, MEDLINE, and LitCOVID on 3 December 2020. STUDY SELECTION Systematic reviews synthesizing data on PWD exposed to SARS-CoV-2 infection, reporting data on confirmed SARS-CoV-2 infection, admission to hospital and/or to intensive care unit (ICU) with COVID-19, and death with COVID-19 were used. DATA EXTRACTION One reviewer appraised and extracted data; data were checked by a second. DATA SYNTHESIS Data from 112 systematic reviews were narratively synthesized and displayed using effect direction plots. Reviews provided consistent evidence that diabetes is a risk factor for severe disease and death from COVID-19. Fewer data were available on ICU admission, but where available, these data also signaled increased risk. Within PWD, higher blood glucose levels both prior to and during COVID-19 illness were associated with worse COVID-19 outcomes. Type 1 diabetes was associated with worse outcomes than type 2 diabetes. There were no appropriate data for discerning whether diabetes was a risk factor for acquiring SARS-CoV-2 infection. LIMITATIONS Due to the nature of the review questions, the majority of data contributing to included reviews come from retrospective observational studies. Reviews varied in the extent to which they assessed risk of bias. CONCLUSIONS There are no data on whether diabetes predisposes to infection with SARS-CoV-2. Data consistently show that diabetes increases risk of severe COVID-19. As both diabetes and worse COVID-19 outcomes are associated with socioeconomic disadvantage, their intersection warrants particular attention.
Shape registration with learned deformations for 3D shape reconstruction from sparse and incomplete point clouds
Authors: Xiang Chen, Nishant Ravikumar, Yan Xia, Rahman Attar, Andres Diaz-Pinto, Stefan K Piechnik, Stefan Neubauer, Steffen E Petersen, Alejandro F Frangi
Journal: Medical Image Analysis (2021)

Shape reconstruction from sparse point clouds/images is a challenging and relevant task required for a variety of applications in computer vision and medical image analysis (e.g. surgical navigation, cardiac motion analysis, augmented/virtual reality systems). A subset of such methods, viz. 3D shape reconstruction from 2D contours, is especially relevant for computer-aided diagnosis and intervention applications involving meshes derived from multiple 2D image slices, views or projections. We propose a deep learning architecture, coined Mesh Reconstruction Network (MR-Net), which tackles this problem. MR-Net enables accurate 3D mesh reconstruction in real-time despite missing data and with sparse annotations. Using 3D cardiac shape reconstruction from 2D contours defined on short-axis cardiac magnetic resonance image slices as an exemplar, we demonstrate that our approach consistently outperforms state-of-the-art techniques for shape reconstruction from unstructured point clouds. Our approach can reconstruct 3D cardiac meshes to within 2.5-mm point-to-point error, concerning the ground-truth data (the original image spatial resolution is ∼1.8×1.8×10mm3). We further evaluate the robustness of the proposed approach to incomplete data, and contours estimated using an automatic segmentation algorithm. MR-Net is generic and could reconstruct shapes of other organs, making it compelling as a tool for various applications in medical image analysis.
Medical care will be prioritised in tackling CO <sub>2</sub> shortages, says government
Authors: Gareth Iacobucci
Journal: BMJ (2021)

The UK government has vowed that continuity of treatment and access to NHS services will be “top priorities” in mitigating against ongoing carbon dioxide shortages, amid concerns that a range of medical and surgical services could be affected.

The covid vaccination programme is one area that depends on a steady supply of carbon dioxide as it uses dry ice as a cooling product. CO2 is also used in minimal invasive surgeries such as laparoscopy, endoscopy, and arthroscopy and in cryotherapy for removals of warts, moles, and skin tags.

The government said it was monitoring the effect of the shortage across …