tbuckley/cabot-search huggingface dataset:
Practical considerations for quantitative clinical SPECT/CT imaging of alpha particle emitting radioisotopes
Authors: Nadia Benabdallah, William Scheve, Nicholas Dunn, Delynn Silvestros, Paul Schelker, Diane Abou, Uday Jammalamadaka, Richard Laforest, Zekun Li, Jonathan Liu, David H Ballard, Nichole M Maughan, Hiram Gay, Brian C Baumann, Robert F Hobbs, Buck Rogers, Amir Iravani, Abhinav K Jha, Farrokh Dehdashti, Daniel L J Thorek
Journal: Theranostics (2021)

Rationale: Alpha particle emitting radiopharmaceuticals are generating considerable interest for the treatment of disseminated metastatic disease. Molecular imaging of the distribution of these agents is critical to safely and effectively maximize the clinical potential of this emerging drug class. The present studies aim to investigate the feasibility and limitations of quantitative SPECT for 223Ra, 225Ac and 227Th. Methods: Three state-of-the-art SPECT/CT systems were investigated: the GE Discovery NM/CT 670, the GE Optima NM/CT 640, and the Siemens Symbia T6. A series of phantoms, including the NEMA IEC Body phantom, were used to compare and calibrate each camera. Additionally, anthropomorphic physical tumor and vertebrae phantoms were developed and imaged to evaluate the quantitative imaging protocol. Results: This work describes and validates a methodology to calibrate each clinical system. The efficiency of each gamma camera was analyzed and compared. Using the calibration factors obtained with the NEMA phantom, we were able to quantify the activity in 3D-printed tissue phantoms with an error of 2.1%, 3.5% and 11.8% for 223Ra, 225Ac, and 227Th, respectively. Conclusion: The present study validates that quantitative SPECT/CT imaging of 223Ra, 225Ac, and 227Th is achievable but that careful considerations for camera configuration are required. These results will aid in future implementation of SPECT-based patient studies and will help to identify the limiting factors for accurate image-based quantification with alpha particle emitting radionuclides.
Intratumoral expression of interleukin 23 variants using oncolytic vaccinia virus elicit potent antitumor effects on multiple tumor models via tumor microenvironment modulation
Authors: Lingjuan Chen, Hongqi Chen, Junjie Ye, Yan Ge, Haiyan Wang, Enyong Dai, Jinghua Ren, Weilin Liu, Congrong Ma, Songguang Ju, Z. Sheng Guo, Zuqiang Liu, David L. Bartlett
Journal: Theranostics (2021)

Background: Newly emerging cancer immunotherapy has led to significant progress in cancer treatment; however, its efficacy is limited in solid tumors since the majority of them are "cold" tumors. Oncolytic viruses, especially when properly armed, can directly target tumor cells and indirectly modulate the tumor microenvironment (TME), resulting in "hot" tumors. These viruses can be applied as a cancer immunotherapy approach either alone or in combination with other cancer immunotherapies. Cytokines are good candidates to arm oncolytic viruses. IL-23, an IL-12 cytokine family member, plays many roles in cancer immunity. Here, we used oncolytic vaccinia viruses to deliver IL-23 variants into the tumor bed and explored their activity in cancer treatment on multiple tumor models. Methods: Oncolytic vaccinia viruses expressing IL-23 variants were generated by homologue recombination. The characteristics of these viruses were in vitro evaluated by RT-qPCR, ELISA, flow cytometry and cytotoxicity assay. The antitumor effects of these viruses were evaluated on multiple tumor models in vivo and the mechanisms were investigated by RT-qPCR and flow cytometry. Results: IL-23 prolonged viral persistence, probably mediated by up-regulated IL-10. The sustainable IL-23 expression and viral oncolysis elevated the expression of Th1 chemokines and antitumor factors such as IFN-γ, TNF-α, Perforin, IL-2, Granzyme B and activated T cells in the TME, transforming the TME to be more conducive to antitumor immunity. This leads to a systemic antitumor effect which is dependent on CD8+ and CD4+ T cells and IFN-γ. Oncolytic vaccinia viruses could not deliver stable IL-23A to the tumor, attributed to the elevated tristetraprolin which can destabilize the IL-23A mRNA after the viral treatment; whereas vaccinia viruses could deliver membrane-bound IL-23 to elicit a potent antitumor effect which might avoid the possible toxicity normally associated with systemic cytokine exposure. Conclusion: Either secreted or membrane-bound IL-23-armed vaccinia virus can induce potent antitumor effects and IL-23 is a candidate cytokine to arm oncolytic viruses for cancer immunotherapy.
A phase II evaluation of pembrolizumab in recurrent microsatellite instability-high (MSI-H) endometrial cancer patients with Lynch-like versus MLH-1 methylated characteristics (NCT02899793)
Authors: S. Bellone, D.M. Roque, E.R. Siegel, N. Buza, P. Hui, E. Bonazzoli, A. Guglielmi, L. Zammataro, N. Nagarkatti, S. Zaidi, J. Lee, D.-A. Silasi, G.S. Huang, V. Andikyan, S. Damast, M. Clark, M. Azodi, P.E. Schwartz, J. Tymon-Rosario, J. Harold, D. Mauricio, B. Zeybek, G. Menderes, G. Altwerger, E. Ratner, L.B. Alexandrov, A. Iwasaki, Y. Kong, E. Song, W. Dong, J. Elvin, J. Choi, A.D. Santin
Journal: Annals of Oncology (2021)
NEED FOR SPEED - BLUNT CARDIAC INJURY
Authors: Sagar Vadhar, Paul Secheresiu, Zeel Patel, Brian Henstenburg, Desire Guthier, Akhil Kher, Lekha Racharla, Rahul Gupta, Tarick Sheikh, Bilal Saqi, Umair Tariq, Shailendra Singh, Daniel Makowski
Journal: Journal of the American College of Cardiology (2021)
Sendai virus-based immunoadjuvant in hydrogel vaccine intensity-modulated dendritic cells activation for suppressing tumorigenesis
Authors: Bin Zheng, Wenchang Peng, Lin Gan, Mingming Guo, Shuchao Wang, Xiao-Dong Zhang, Dong Ming
Journal: Bioactive Materials (2021)

The conventional immunoadjuvants in vaccine have weak effect on stimulating antigen presentation and activating anti-tumor immunity. Unexpectedly, we discovered that non-pathogenic Sendai virus (SeV) could activate antigen-presenting cells (APCs) represented by dendritic cells (DCs). Here, we designed an injectable SeV-based hydrogel vaccine (SHV) to execute multi-channel recruitment and stimulation of DCs for boosting the specific immune response against tumors. After the release of the NIR-triggered antigens from tumor cells, dendritic cells around the vaccine efficiently transport the antigens to lymph nodes and present them to T lymphocytes, thereby inducing systemic anti-tumor immune memory. Our findings demonstrated that the SHV with excellent universality, convenience and flexibility has achieved better immune protection effects in inhibiting the occurrence of melanoma and breast cancer. In conclusion, the SHV system might serve as the next generation of personalized anti-tumor vaccines with enhanced features over standard vaccination regimens, and represented an alternative way to suppress tumorigenesis.
Raman microspectroscopy and Raman imaging reveal biomarkers specific for thoracic aortic aneurysms
Authors: Kaori Sugiyama, Julia Marzi, Julia Alber, Eva M. Brauchle, Masahiro Ando, Yoshito Yamashiro, Bhama Ramkhelawon, Katja Schenke-Layland, Hiromi Yanagisawa
Journal: Cell Reports Medicine (2021)
PERIOPERATIVE MANAGEMENT OF ORAL ANTICOAGULANTS IN CARDIAC SURGERY, WHEN IS THE OPTIMAL STOP TIME
Authors: Yana Shamiss, Zahra Azizi, Rebecca Malcolm, Sarah Donegan, Jenny Gao-Kang, Marina Batrak, Alireza Samani, Colleen Owen, Gabrielle Falvey, Farzaneh Sharifzad, Sereena Nath, Nikhil Nath, Jamie Forman, Kaitlin Stitz, Rohan Dadak, Julia Peniston, Sara Tamjidi, Roshni Kohli, Niala Kalliecharan, Lana Chan-Smith, Caroline Teng, Kevin Teoh, Stacy O’Blenes, Yaariv Khaykin, Charles Peniston
Journal: Journal of the American College of Cardiology (2021)
Distinct Foxp3 enhancer elements coordinate development, maintenance, and function of regulatory T cells
Authors: Ryoji Kawakami, Yohko Kitagawa, Kelvin Y. Chen, Masaya Arai, Daiya Ohara, Yamami Nakamura, Keiko Yasuda, Motonao Osaki, Norihisa Mikami, Caleb A. Lareau, Hitomi Watanabe, Gen Kondoh, Keiji Hirota, Naganari Ohkura, Shimon Sakaguchi
Journal: Immunity (2021)
Evidence for Selection in the Abundant Accessory Gene Content of a Prokaryote Pangenome
Authors: Fiona J Whelan, Rebecca J Hall, James O McInerney
Journal: Molecular Biology and Evolution (2021)

A pangenome is the complete set of genes (core and accessory) present in a phylogenetic clade. We hypothesize that a pangenome's accessory gene content is structured and maintained by selection. To test this hypothesis, we interrogated the genomes of 40 Pseudomonas species for statistically significant coincident (i.e., co-occurring/avoiding) gene patterns. We found that 86.7% of common accessory genes are involved in ≥1 coincident relationship. Further, genes that co-occur and/or avoid each other-but are not vertically inherited-are more likely to share functional categories, are more likely to be simultaneously transcribed, and are more likely to produce interacting proteins, than would be expected by chance. These results are not due to coincident genes being adjacent to one another on the chromosome. Together, these findings suggest that the accessory genome is structured into sets of genes that function together within a given strain. Given the similarity of the Pseudomonas pangenome with open pangenomes of other prokaryotic species, we speculate that these results are generalizable.
Bovine γ‐globulin, lactoferrin, and lactoperoxidase are relevant bovine milk allergens in patients with α‐Gal syndrome
Authors: Marija Perusko, Danijela Apostolovic, Mensiena Berentje Geertje Kiewiet, Jeanette Grundström, Carl Hamsten, Maria Starkhammar, Tanja Cirkovic Velickovic, Marianne van Hage
Journal: Allergy (2021)

Mammalian meat is the most common trigger of the allergic reactions in patients with α-Gal syndrome (AGS). Milk and dairy, although less often, also cause a significant number of allergic manifestations. The aim of this study was to identify α-Gal-containing bovine milk proteins with allergenic properties among AGS patients.Thirty-eight AGS patients with IgE to milk were included in the study. Milk proteins were analyzed for the presence of α-Gal and for binding by patients' IgE using immunoblot, ImmunoCAP, and inhibition ELISA. Allergenicity of milk and milk proteins was assessed by basophil activation test.More than half of the AGS patients reported allergic reactions to milk or dairy products. Bovine γ-globulin (BGG), lactoferrin (LF), and lactoperoxidase (LPO) were identified as α-Gal carrying proteins which were recognized by AGS patients' IgE. Whey mirrored the anti-α-Gal and IgE reactivity of BGG, LF, and LPO. Eighty-nine percent of the patients displayed IgE to BGG, 91% to LF, and 57% to LPO. Inhibition of α-Gal-specific IgE binding was achieved by BGG, LF, LPO, and whey. These proteins also activated AGS patients' basophils. Interestingly, at lower concentrations, LF was the most potent inhibitor of IgE binding, and the most potent activator of basophils.BGG, LF, and LPO were all found to be relevant milk α-Gal-containing glycoproteins that bound AGS patients' IgE antibodies and activated their basophils. These proteins are probably involved in the allergic reactions to milk in AGS patients. LPO was for the first time shown to be an allergen.
N-cadherin mediates the migration of bone marrow-derived mesenchymal stem cells toward breast tumor cells
Authors: Sanghyuk Choi, Jinyeong Yu, Wootak Kim, Ki-Sook Park
Journal: Theranostics (2021)

Rationale: Bone marrow-derived mesenchymal stem cells (BM-MSCs) recruited into breast tumors regulate the behavior of tumor cells via various mechanisms and affect clinical outcomes. Although signaling molecules, such as transforming growth factor β (TGF-β), are known to transmit signals between BM-MSCs and breast tumor cells for recruiting BM-MSCs, it is unclear which specific intrinsic molecules involved in cell motility mediate the migration of BM-MSCs into breast tumor. It is also unclear as to how specific intrinsic molecules contribute to the migration. Methods: Conditioned medium (CM) from breast tumor cells (MCF-7 and MDA-MB-231) that simulates breast tumor secreting TGF-β was used to examine the migration of BM-MSCs into breast tumors. A three-dimensional migration assay was performed to investigate the collective migration of BM-MSCs, maintaining cell-cell adhesion, toward breast tumor cells. Results: N-cadherin formed adherens junction-like structures on the intercellular borders of BM-MSCs, and TGF-β increased the expression of N-cadherin on these borders. Knockdown of Smad4 impaired the TGF-β-mediated increase in N-cadherin expression in BM-MSCs, but inhibitors of non-canonical TGF-β pathways, such as extracellular signal-regulated kinases, Akt, and p38, did not affect it. siRNA-mediated knockdown of N-cadherin and Smad4 impaired the migration of BM-MSCs in response to TGF-β. Conditioned medium from breast tumor cells also enhanced the expression of N-cadherin in BM-MSCs, but inactivation of TGF-β type 1 receptor (TGFBR1) with SB505124 and TGFBR1 knockdown abolished the increase in N-cadherin expression. BM-MSCs collectively migrated toward CM from MDA-MB-231 in vitro while maintaining cell-cell adhesion through N-cadherin. Knockdown of N-cadherin abolished the migration of BM-MSCs toward the CM from breast tumor cells. Conclusion: In the present study, we identified N-cadherin, an intrinsic transmembrane molecule in adherens junction-like structures, on BM-MSCs as a mediator for the migration of these cells toward breast tumor. The expression of N-cadherin increases on the intercellular borders of BM-MSCs through the TGF-β canonical signaling and they collectively migrate in response to breast tumor cells expressing TGF-β via N-cadherin-dependent cell-cell adhesion. We, herein, introduce a novel promising strategy for controlling and re-engineering the breast tumor microenvironment.
Increasing mTORC1 Pathway Activity or Methionine Supplementation during Pregnancy Reverses the Negative Effect of Maternal Malnutrition on the Developing Kidney
Authors: Yaniv Makayes, Elad Resnick, Liad Hinden, Elina Aizenshtein, Tomer Shlomi, Raphael Kopan, Morris Nechama, Oded Volovelsky
Journal: Journal of the American Society of Nephrology (2021)

Low nephron number at birth is associated with a high risk of CKD in adulthood because nephrogenesis is completed
Patient-specific iPSC-derived cardiomyocytes reveal abnormal regulation of <i>FGF16</i> in a familial atrial septal defect
Authors: Lingqun Ye, You Yu, Zhen-Ao Zhao, Dandan Zhao, Xuan Ni, Yong Wang, Xing Fang, Miao Yu, Yongming Wang, Jun-Ming Tang, Ying Chen, Zhenya Shen, Wei Lei, Shijun Hu
Journal: Cardiovascular Research (2021)

Abstract Aims Congenital heart disease (CHD) frequently occurs in newborns due to abnormal formation of the heart or major blood vessels. Mutations in the GATA4 gene, which encodes GATA binding protein 4, are responsible for atrial septal defect (ASD), a common CHD. This study aims to gain insights into the molecular mechanisms of CHD using human-induced pluripotent stem cells (iPSCs) from a family cohort with ASD. Methods and results Patient-specific iPSCs possess the same genetic information as the donor and can differentiate into various cell types from all three germ layers in vitro, thus presenting a promising approach for disease modelling and molecular mechanism research. Here, we generated a patient-specific iPSC line (iPSC-G4T280M) from a family cohort carrying a hereditary ASD mutation in GATA4 gene (T280M), as well as a human embryonic stem cell line (ESC-G4T280M) carrying the isogenic T280M mutation using the CRISPR/Cas9 genome editing method. The GATA4-mutant iPSCs and ESCs were then differentiated into cardiomyocytes (CMs) to model GATA4 mutation-associated ASD. We observed an obvious defect in cell proliferation in cardiomyocytes derived from both GATA4T280M-mutant iPSCs (iPSC-G4T280M-CMs) and ESCs (ESC-G4T280M-CMs), while the impaired proliferation ability of iPSC-G4T280M-CMs could be restored by gene correction. Integrated analysis of RNA-Seq and ChIP-Seq data indicated that FGF16 is a direct target of wild-type GATA4. However, the T280M mutation obstructed GATA4 occupancy at the FGF16 promoter region, leading to impaired activation of FGF16 transcription. Overexpression of FGF16 in GATA4-mutant cardiomyocytes rescued the cell proliferation defect. The direct relationship between GATA4T280M and ASD was demonstrated in a human iPSC model for the first time. Conclusions In summary, our study revealed the molecular mechanism of the GATA4T280M mutation in ASD. Understanding the roles of the GATA4-FGF16 axis in iPSC-CMs will shed light on heart development and provide novel insights for the treatment of ASD and other CHD disorders.
CIRCULATING VERY SMALL TRIGLYCERIDE-RICH LIPOPROTEINS ARE REDUCED EARLY AFTER BARIATRIC SURGERY
Authors: Ruina Zhang, BingXue Lin, Ariya Chaloemtoem, Marcin Falis, Manish Parikh, Jeffrey Berger, Edward Fisher, Florencia Schlamp, Sean Heffron
Journal: Journal of the American College of Cardiology (2021)
Women in Stroke Trials—A Tale of Perpetual Inequity in Cardiovascular Research
Authors: Safi U. Khan, Erin D. Michos
Journal: JAMA Neurology (2021)

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J WAVES REACHING TO LV INFERIOR WALL LEADS MAY PREDICT THE PRESENCE OF ORGANIZED MYOCARDIAL FIBROTIC OR FAT CHANGE IN SURVIVORS OF VENTRICULAR FIBRILLATION WITHOUT ISCHEMIC HEART DISEASE
Authors: Nobusada Funabashi, Koki Nakamura, Masahiro Okamoto, Shigeto Naito, Yoshio Kobayashi
Journal: Journal of the American College of Cardiology (2021)
BURDEN OF ATRIAL FIBRILLATION OR ATRIAL FLUTTER IN DIASTOLIC HEART FAILURE HOSPITALIZATIONS: INSIGHT FROM 2017 NATIONAL INPATIENT SAMPLE
Authors: Harshith Thyagaturu, Kashyap Shah, Bishesh Shrestha, Sittinun Thangjui, Meghnath Reddy
Journal: Journal of the American College of Cardiology (2021)
Incidental Serous Cystadenoma Presenting as a Photopenic Pancreatic Defect on 18F-Fluciclovine PET/CT
Authors: Jeffrey Waltz, Megan K. Mercer, Genta Dani, William J. Rieter
Journal: Clinical Nuclear Medicine (2021)

Abstract 18 F-fluciclovine (Axumin) PET/CT has been widely used for the evaluation of biochemically recurrent prostate cancer following prior treatment. While lymph node and visceral organ metastases typically show increased radiotracer uptake, altered patterns of normal physiologic activity may also provide insight into other disease processes. We present a case of an incidental pancreatic head mass presenting as a photopenic defect on a staging 18 F-fluciclovine PET/CT, which was subsequently confirmed to be a benign serous cystadenoma using multisequence MRI.
Risk of colorectal cancer in first degree relatives of patients with colorectal polyps: nationwide case-control study in Sweden
Authors: Mingyang Song, Louise Emilsson, Bjorn Roelstraete, Jonas F Ludvigsson
Journal: BMJ (2021)

Abstract Objective To assess the risk of colorectal cancer (CRC) in first degree relatives (parents and full siblings) of patients with precursor lesions (polyps) for CRC. Design Case-control study. Setting Linkage to the multi-generation register and gastrointestinal ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) histopathology cohort in Sweden. Participants 68 060 patients with CRC and 333 753 matched controls. Main outcome measures Multivariable adjusted odds ratios of CRC according to the number of first degree relatives with a colorectal polyp and the histology of polyps and age at diagnosis in first degree relatives. Subgroup analysis was also performed according to age at CRC diagnosis and evaluated the joint association of family history of colorectal polyps and family history of CRC. Results After adjusting for family history of CRC and other covariates, having a first degree relative with a colorectal polyp (8.4% (5742/68 060) in cases and 5.7% (18 860/333 753) in controls) was associated with a higher risk of CRC (odds ratio 1.40, 95% confidence interval 1.35 to 1.45). The odds ratios ranged from 1.23 for those with hyperplastic polyps to 1.44 for those with tubulovillous adenomas. To better put this risk in perspective, the age specific absolute risk of colon and rectal cancers was estimated according to family history of polyps based on the 2018 national CRC incidence in Sweden. For example, the absolute risk of colon cancer in individuals aged 60-64 years with and without a family history of colorectal polyp was, respectively, 94.3 and 67.9 per 100 000 for men and 89.1 and 64.1 per 100 000 for women. The association between family history of polyps and CRC risk was strengthened by the increasing number of first degree relatives with polyps (≥2 first degree relatives: 1.70, 1.52 to 1.90, P&lt;0.001 for trend) and decreasing age at polyp diagnosis (&lt;50 years: 1.77, 1.57 to 1.99, P&lt;0.001 for trend). A particularly strong association was found for early onset CRC diagnosed before age 50 years (≥2 first degree relatives: 3.34, 2.05 to 5.43, P=0.002 for heterogeneity by age of CRC diagnosis). In the joint analysis, the odds ratio of CRC for individuals with two or more first degree relatives with polyps but no CRC was 1.79 (1.52 to 2.10), with one first degree relative with CRC but no polyps was 1.70 (1.65 to 1.76), and with two or more first degree relatives with both polyps and CRC was 5.00 (3.77 to 6.63) (P&lt;0.001 for interaction). Conclusions After adjusting for family history of CRC, the siblings and children of patients with colorectal polyps are still at higher risk of CRC, particularly early onset CRC. Early screening for CRC might be considered for first degree relatives of patients with polyps.
REVASCULARIZATION TIMING OF NON-CULPRIT ARTERY FOR ST-ELEVATION MYOCARDIAL INFARCTION WITH MULTIVESSEL DISEASE: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS OF RANDOMIZED TRIALS
Authors: Hiroki Ueyama, Toshiki Kuno, Keisuke Yasumura, Yuliya Vengrenyuk, Hisato Takagi, Nitin Barman, Javed Suleman, Amerjeet Banning, Bianca Boxama-de Klerk, Anthony Gershlick, Pieter Smits, Annapoorna Kini, Samin Sharma
Journal: Journal of the American College of Cardiology (2021)