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Article ; Online: ChatGPT and the Law of the Horse.

Cheung, Alexander T M / Nasir-Moin, Mustafa / Oermann, Eric K

The American journal of bioethics : AJOB

2023 Volume 23, Issue 10, Page(s) 55–57

MeSH term(s)	Horses ; Animals ; Bioethics
Language	English
Publishing date	2023-10-09
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2060433-6
ISSN	1536-0075 ; 1526-5161
ISSN (online)	1536-0075
ISSN	1526-5161
DOI	10.1080/15265161.2023.2250279
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Article ; Online: Immunomodulatory role of thrombin in cancer progression.

Alexander, Eric T / Gilmour, Susan K

Molecular carcinogenesis

2022 Volume 61, Issue 6, Page(s) 527–536

Abstract: ... immunosuppressive cell populations including myeloid derived suppresser cells, M2-like macrophages, and T regulatory ...

Abstract	Coagulation proteases and the generation of thrombin are increased in tumors. In addition, chemotherapeutic agents commonly used to treat malignant cancers can exacerbate cancer-associated thromboses. Thrombin can modify tumor cell behavior directly through the activation of protease-activated receptors (PAR) or indirectly by generating fibrin matrices. In addition to its role in generating fibrin to promote hemostasis, thrombin acts directly on multiple effector cells of the immune system impacting both acute and chronic inflammatory processes. Thrombin-mediated release of interleukin-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 leads to the accumulation of multiple tumor-infiltrating immunosuppressive cell populations including myeloid derived suppresser cells, M2-like macrophages, and T regulatory cells. Ablation of PAR-1 from the tumor microenvironment, but not the tumor, has been shown to dramatically reduce tumor growth and metastasis in multiple tumor models. Thrombin-activated platelets release immunosuppressive cytokines including transforming growth factor-β that can inhibit natural killer cell activity, helping tumor cells to evade host immunosurveillance. Taken together, there is strong evidence that thrombin influences cancer progression via multiple mechanisms, including the tumor immune response, with thrombin emerging as a target for novel therapeutic strategies for cancer.
MeSH term(s)	Fibrin ; Humans ; Immunity ; Neoplasms/pathology ; Receptor, PAR-1/physiology ; Thrombin/pharmacology ; Tumor Microenvironment
Chemical Substances	Receptor, PAR-1 ; Fibrin (9001-31-4) ; Thrombin (EC 3.4.21.5)
Language	English
Publishing date	2022-03-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	1004029-8
ISSN	1098-2744 ; 0899-1987
ISSN (online)	1098-2744
ISSN	0899-1987
DOI	10.1002/mc.23398
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Article: Loss of Anti-Tumor Efficacy by Polyamine Blocking Therapy in GCN2 Null Mice.

Alexander, Eric T / Fahey, Erin / Phanstiel, Otto / Gilmour, Susan K

Biomedicines

2023 Volume 11, Issue 10

Abstract: GCN2 is one of the main sensors of amino acid starvation stress, and its activation in the stressful tumor microenvironment plays a crucial role in tumor survival and progression. We hypothesized that elevated polyamine biosynthesis and subsequent ... ...

Abstract	GCN2 is one of the main sensors of amino acid starvation stress, and its activation in the stressful tumor microenvironment plays a crucial role in tumor survival and progression. We hypothesized that elevated polyamine biosynthesis and subsequent depletion of precursor arginine activates GCN2, thus rewiring metabolism to support tumor cell survival and drive myeloid immunosuppressive function. We sought to determine if the anti-tumor efficacy of a polyamine blocking therapy (PBT) may be mediated by its effect on GCN2. Unlike wild-type mice, PBT treatment in GCN2 knockout mice bearing syngeneic B16.F10 or EG7 tumors resulted in no tumor growth inhibition and no changes in the profile of infiltrating tumor immune cells. Studies with murine bone marrow cell cultures showed that increased polyamine metabolism and subsequent arginine depletion and GCN2 activation played an essential role in the generation and cytoprotective autophagy of myeloid derived suppressor cells (MDSCs) as well as the M2 polarization and survival of macrophages, all of which were inhibited by PBT. In all, our data suggest that polyamine-dependent GCN2 signaling in stromal cells promotes tumor growth and the development of the immunosuppressive tumor microenvironment, and that the PBT anti-tumor effect is mediated, at least in part, by targeting GCN2.
Language	English
Publishing date	2023-10-05
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines11102703
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Article ; Online: Petascale pipeline for precise alignment of images from serial section electron microscopy.

Popovych, Sergiy / Macrina, Thomas / Kemnitz, Nico / Castro, Manuel / Nehoran, Barak / Jia, Zhen / Bae, J Alexander / Mitchell, Eric / Mu, Shang / Trautman, Eric T / Saalfeld, Stephan / Li, Kai / Seung, H Sebastian

Nature communications

2024 Volume 15, Issue 1, Page(s) 289

Abstract: The reconstruction of neural circuits from serial section electron microscopy (ssEM) images is being accelerated by automatic image segmentation methods. Segmentation accuracy is often limited by the preceding step of aligning 2D section images to create ...

Abstract	The reconstruction of neural circuits from serial section electron microscopy (ssEM) images is being accelerated by automatic image segmentation methods. Segmentation accuracy is often limited by the preceding step of aligning 2D section images to create a 3D image stack. Precise and robust alignment in the presence of image artifacts is challenging, especially as datasets are attaining the petascale. We present a computational pipeline for aligning ssEM images with several key elements. Self-supervised convolutional nets are trained via metric learning to encode and align image pairs, and they are used to initialize iterative fine-tuning of alignment. A procedure called vector voting increases robustness to image artifacts or missing image data. For speedup the series is divided into blocks that are distributed to computational workers for alignment. The blocks are aligned to each other by composing transformations with decay, which achieves a global alignment without resorting to a time-consuming global optimization. We apply our pipeline to a whole fly brain dataset, and show improved accuracy relative to prior state of the art. We also demonstrate that our pipeline scales to a cubic millimeter of mouse visual cortex. Our pipeline is publicly available through two open source Python packages.
MeSH term(s)	Animals ; Mice ; Imaging, Three-Dimensional/methods ; Microscopy, Electron ; Brain/diagnostic imaging ; Image Processing, Computer-Assisted/methods
Language	English
Publishing date	2024-01-04
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-44354-0
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Article: Measuring pulsatile cortical blood flow and volume during carotid endarterectomy.

Zavriyev, Alexander I / Kaya, Kutlu / Wu, Kuan Cheng / Pierce, Eric T / Franceschini, Maria Angela / Robinson, Mitchell B

Biomedical optics express

2024 Volume 15, Issue 3, Page(s) 1355–1369

Abstract: Carotid endarterectomy (CEA) involves removal of plaque in the carotid artery to reduce the risk of stroke and improve cerebral perfusion. This study aimed to investigate the utility of assessing pulsatile blood volume and flow during CEA. Using a ... ...

Abstract	Carotid endarterectomy (CEA) involves removal of plaque in the carotid artery to reduce the risk of stroke and improve cerebral perfusion. This study aimed to investigate the utility of assessing pulsatile blood volume and flow during CEA. Using a combined near-infrared spectroscopy/diffuse correlation spectroscopy instrument, pulsatile hemodynamics were assessed in 12 patients undergoing CEA. Alterations to pulsatile amplitude, pulse transit time, and beat morphology were observed in measurements ipsilateral to the surgical side. The additional information provided through analysis of pulsatile hemodynamic signals has the potential to enable the discovery of non-invasive biomarkers related to cortical perfusion.
Language	English
Publishing date	2024-02-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	2572216-5
ISSN	2156-7085
ISSN	2156-7085
DOI	10.1364/BOE.507730
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Article ; Online: Regional Anesthesia of the Dentition in Bennett's Wallaby (

Walker, Bridget / Stone, Amy / Langan, Jennifer N / Hostnik, Eric T / Alexander, Amy B

Journal of veterinary dentistry

2023 , Page(s) 8987564231219179

Abstract: Dental disease is common in captive-managed macropods, including Bennett's wallabies, and is a significant cause of morbidity and mortality. Dental extractions and debridement of diseased tissue is often necessary for those undergoing treatment for ... ...

Abstract	Dental disease is common in captive-managed macropods, including Bennett's wallabies, and is a significant cause of morbidity and mortality. Dental extractions and debridement of diseased tissue is often necessary for those undergoing treatment for severe dental disease. Regional anesthesia of the dentition is considered standard of care for domestic animals undergoing orofacial surgery, however, it is not routinely performed in macropods due to limited information on dental anatomy and block approaches. Regional block descriptions for the infraorbital, maxillary, inferior alveolar, and mental blocks in domestic dogs and cats were evaluated and adapted for use in Bennett's wallabies based on descriptions of their anatomy and examination of 2 skulls. These approaches were then performed on cadaver heads with iohexol and methylene blue dye, and block placement was assessed on computed tomography scans and by gross dissection. All block approaches described in this study resulted in appropriate placement of regional anesthesia of the dentition in Bennett's wallabies. They can thus be used by clinicians to improve the intra and postoperative pain control of patients and provide a high level of veterinary care.
Language	English
Publishing date	2023-12-15
Publishing country	United States
Document type	Journal Article
ISSN	2470-4083
ISSN (online)	2470-4083
DOI	10.1177/08987564231219179
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Article ; Online: Petascale pipeline for precise alignment of images from serial section electron microscopy

Sergiy Popovych / Thomas Macrina / Nico Kemnitz / Manuel Castro / Barak Nehoran / Zhen Jia / J. Alexander Bae / Eric Mitchell / Shang Mu / Eric T. Trautman / Stephan Saalfeld / Kai Li / H. Sebastian Seung

Nature Communications, Vol 15, Iss 1, Pp 1-

2024 Volume 15

Abstract: Abstract The reconstruction of neural circuits from serial section electron microscopy (ssEM) images is being accelerated by automatic image segmentation methods. Segmentation accuracy is often limited by the preceding step of aligning 2D section images ... ...

Abstract	Abstract The reconstruction of neural circuits from serial section electron microscopy (ssEM) images is being accelerated by automatic image segmentation methods. Segmentation accuracy is often limited by the preceding step of aligning 2D section images to create a 3D image stack. Precise and robust alignment in the presence of image artifacts is challenging, especially as datasets are attaining the petascale. We present a computational pipeline for aligning ssEM images with several key elements. Self-supervised convolutional nets are trained via metric learning to encode and align image pairs, and they are used to initialize iterative fine-tuning of alignment. A procedure called vector voting increases robustness to image artifacts or missing image data. For speedup the series is divided into blocks that are distributed to computational workers for alignment. The blocks are aligned to each other by composing transformations with decay, which achieves a global alignment without resorting to a time-consuming global optimization. We apply our pipeline to a whole fly brain dataset, and show improved accuracy relative to prior state of the art. We also demonstrate that our pipeline scales to a cubic millimeter of mouse visual cortex. Our pipeline is publicly available through two open source Python packages.
Keywords	Science ; Q
Subject code	006 ; 004
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Assessing Alignment Using GAP Score and Complications for Pedicle Subtraction Osteotomy Revision Surgeries for Sagittal Deformity in Previously Fused Spines Using a Satellite Rod Technique.

Yahanda, Alexander T / Wegner, Adam M / Klineberg, Eric O / Gupta, Munish C

World neurosurgery

2023 Volume 179, Page(s) e262–e268

Abstract: Objective: Pedicle subtraction osteotomy (PSO) is a surgical technique to restore lumbar lordosis in patients with rigid sagittal deformity. Herein, we report on outcomes of a surgical technique utilizing a 4-rod PSO with satellite rods.: Methods: A ... ...

Abstract	Objective: Pedicle subtraction osteotomy (PSO) is a surgical technique to restore lumbar lordosis in patients with rigid sagittal deformity. Herein, we report on outcomes of a surgical technique utilizing a 4-rod PSO with satellite rods. Methods: A retrospective study was performed for a cohort of patients who underwent 4-rod PSO revision surgery for sagittal deformity. Procedures were performed by one surgeon at 2 different academic centers between 2004-2018. Alignment outcomes and complications specifically for revision surgeries in previously fused spines were assessed. Results: 40 patients underwent PSO with the satellite rod technique (n = 29 at L3, 72.5%; n = 7 at L4, 17.5%). Mean PSO angle was 28.7 ± 7.6°. Two patients (5%) had rod fracture necessitating revision surgery at 32 and 34 months. Three patients (7.5%) developed proximal junctional kyphosis (PJK), but none required revision. No patients developed pseudoarthrosis. Mean preoperative sagittal vertical axis (SVA) was 13.5 ± 7.3 cm, which decreased to 4.8 ± 7.3 cm (P = 0.002) postoperatively. Mean preoperative pelvic incidence-lumbar lordosis (PI-LL) mismatch improved from 35.9 ± 16.6° preoperatively to 11.8 ± 14.6° postoperatively (P < 0.001). Mean preoperative pelvic tilt (PT) improved from 34.7 ± 9.8° preoperatively to 30.1 ± 9.0° (P = 0.026) postoperatively. Mean global alignment and proportion (GAP) score improved from 10 ± 2 preoperatively to 8 ± 2 postoperatively (P < 0.001), which was still considered severely disproportioned. Conclusions: Rod failure rate after PSO with the 4-rod satellite configuration was low. SVA, PI-LL mismatch, and PT significantly improved for these previously-fused patients. Mean GAP score also improved, but was still considered severely disproportioned, likely due to the inability of PSO to correct low LL or PT in previously-fused spines.
MeSH term(s)	Humans ; Lordosis/diagnostic imaging ; Lordosis/surgery ; Reoperation ; Retrospective Studies ; Osteotomy/methods ; Kyphosis/diagnostic imaging ; Kyphosis/surgery ; Lumbar Vertebrae/diagnostic imaging ; Lumbar Vertebrae/surgery ; Spinal Fusion/adverse effects ; Spinal Fusion/methods ; Treatment Outcome ; Thoracic Vertebrae/surgery
Language	English
Publishing date	2023-08-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	2534351-8
ISSN	1878-8769 ; 1878-8750
ISSN (online)	1878-8769
ISSN	1878-8750
DOI	10.1016/j.wneu.2023.08.070
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Article ; Online: Patterns of neurological adverse events among a retrospective cohort of patients receiving immune checkpoint inhibitors.

Hunting, John C / Faucheux, Andrew T / Price, Sarah N / Elko, Catherine A / Quattlebaum, Alexander / Bloomer, Chance / Olson, Eric / Petty, William J / Lycan, Thomas W

Immunotherapy

2024 Volume 16, Issue 6, Page(s) 381–390

Abstract: Aim: ...

Abstract	Aim:
MeSH term(s)	Humans ; Immune Checkpoint Inhibitors/adverse effects ; Retrospective Studies ; Brain Neoplasms ; Carcinoma, Renal Cell/drug therapy ; Kidney Neoplasms
Chemical Substances	Immune Checkpoint Inhibitors
Language	English
Publishing date	2024-01-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2495964-9
ISSN	1750-7448 ; 1750-743X
ISSN (online)	1750-7448
ISSN	1750-743X
DOI	10.2217/imt-2023-0273
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Article: Adaptation of Empirical Methods to Predict the LogD of Triazine Macrocycles.

Patterson-Gardner, Casey J / Pavelich, Gretchen M / Cannon, April T / Menke, Alexander J / Simanek, Eric E

ACS medicinal chemistry letters

2023 Volume 14, Issue 10, Page(s) 1378–1382

Abstract: Octanol/water partition coefficients guide drug design, but algorithms do not always accurately predict these values. For cationic triazine macrocycles that adopt a conserved folded shape in solution, common algorithms fall short. Here, the logD values ... ...

Abstract	Octanol/water partition coefficients guide drug design, but algorithms do not always accurately predict these values. For cationic triazine macrocycles that adopt a conserved folded shape in solution, common algorithms fall short. Here, the logD values for 12 macrocycles differing in amino acid choice were predicted and then measured experimentally. On average, AlogP, XlogP, and ChemAxon predictions deviate by 0.9, 2.8, and 3.9 log units, with XlogP overestimating lipophilicity and AlogP and ChemAxon underestimating lipophilicity. Importantly, however, a linear relationship (
Language	English
Publishing date	2023-09-08
Publishing country	United States
Document type	Journal Article
ISSN	1948-5875
ISSN	1948-5875
DOI	10.1021/acsmedchemlett.3c00290
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