37 results on '"Johnson, Philip"'
Search Results
2. Directed ultrafast conformational changes accompany electron transfer in a photolyase as resolved by serial crystallography
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Cellini, Andrea, Shankar, Madan Kumar, Nimmrich, Amke, Hunt, Leigh Anna, Monrroy, Leonardo, Mutisya, Jennifer, Furrer, Antonia, Beale, Emma V., Carrillo, Melissa, Malla, Tek Narsingh, Maj, Piotr, Vrhovac, Lidija, Dworkowski, Florian, Cirelli, Claudio, Johnson, Philip J. M., Ozerov, Dmitry, Stojković, Emina A., Hammarström, Leif, Bacellar, Camila, Standfuss, Jörg, Maj, Michał, Schmidt, Marius, Weinert, Tobias, Ihalainen, Janne A., Wahlgren, Weixiao Yuan, and Westenhoff, Sebastian
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- 2024
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3. Influence of pump laser fluence on ultrafast myoglobin structural dynamics
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Barends, Thomas R. M., Gorel, Alexander, Bhattacharyya, Swarnendu, Schirò, Giorgio, Bacellar, Camila, Cirelli, Claudio, Colletier, Jacques-Philippe, Foucar, Lutz, Grünbein, Marie Luise, Hartmann, Elisabeth, Hilpert, Mario, Holton, James M., Johnson, Philip J. M., Kloos, Marco, Knopp, Gregor, Marekha, Bogdan, Nass, Karol, Nass Kovacs, Gabriela, Ozerov, Dmitry, Stricker, Miriam, Weik, Martin, Doak, R. Bruce, Shoeman, Robert L., Milne, Christopher J., Huix-Rotllant, Miquel, Cammarata, Marco, and Schlichting, Ilme
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- 2024
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4. Salvianolic acid B inhibits thrombosis and directly blocks the thrombin catalytic site
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Neves, Miguel A.D., Ni, Tiffany T., Mackeigan, Daniel T., Shoara, Aron A., Lei, Xi, Slavkovic, Sladjana, Yu, Si-Yang, Stratton, Tyler W., Gallant, Reid C., Zhang, Dan, Xu, Xiaohong Ruby, Fernandes, Cheryl, Zhu, Guangheng, Hu, Xudong, Chazot, Noa, Donaldson, Logan W., Johnson, Philip E., Connelly, Kim, Rand, Margaret, Wang, Yiming, and Ni, Heyu
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- 2024
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5. The RNA binding proteins LARP4A and LARP4B promote sarcoma and carcinoma growth and metastasis
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Coleman, Jennifer C., Tattersall, Luke, Yianni, Val, Knight, Laura, Yu, Hongqiang, Hallett, Sadie R., Johnson, Philip, Caetano, Ana J., Cosstick, Charlie, Ridley, Anne J., Gartland, Alison, Conte, Maria R., and Grigoriadis, Agamemnon E.
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- 2024
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6. Regional Differences in Clinical Presentation and Prognosis of Patients With Post–Sustained Virologic Response Hepatocellular Carcinoma
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Toyoda, Hidenori, Kanneganti, Mounika, Melendez-Torres, Jonathan, Parikh, Neehar D., Jalal, Prasun K., Piñero, Federico, Mendizabal, Manuel, Ridruejo, Ezequiel, Cheinquer, Hugo, Casadei-Gardini, Andrea, Weinmann, Arndt, Peck-Radosavljevic, Markus, Dufour, Jean-Francois, Radu, Pompilia, Shiha, Gamal, Soliman, Riham, Sarin, Shiv K., Kumar, Manoj, Wang, Jing-Houng, Tangkijvanich, Pisit, Sukeepaisarnjaroen, Wattana, Atsukawa, Masanori, Uojima, Haruki, Nozaki, Akito, Nakamuta, Makoto, Takaguchi, Koichi, Hiraoka, Atsushi, Abe, Hiroshi, Matsuura, Kentaro, Watanabe, Tsunamasa, Shimada, Noritomo, Tsuji, Kunihiko, Ishikawa, Toru, Mikami, Shigeru, Itobayashi, Ei, Singal, Amit G., and Johnson, Philip J.
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- 2024
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7. Ligand-Induced Folding in a Dopamine-Binding DNA Aptamer
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Kaiyum, Yunus, primary, Chao, Emily, Hoi Pui, additional, Nguyen, Minh-Dat, additional, Mackereth, Cameron, additional, Dauphin-Ducharme, Philippe, additional, and Johnson, Philip, additional
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- 2024
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8. Truncations and in silico Docking to Enhance the Analytical Response of Aptamer-Based Biosensors
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Nguyen, Minh-Dat, primary, Osborne, Meghan, additional, Prevot, Guy Terence, additional, Churcher, Zachary, additional, Johnson, Philip, additional, Simine, Lena, additional, and Dauphin Ducharme, Philippe, additional
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- 2024
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9. Equine metabolic syndrome: part 1
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Johnson, Philip J, primary
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- 2024
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10. Pyoverdine binding aptamers and label-free electrochemical detection of pseudomonads.
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Anisuzzaman, Sharif, Alimoradi, Nima, Singappuli-Arachchige, Dilini, Banerjee, Soma, Pogorelko, Gennady V., Kaiyum, Yunus A., Johnson, Philip E., Shrotriya1,3, Pranav, Nilsen-Hamilton, Marit, Xixia Liu, Kun Li, and Zhaofeng Luo
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APTAMERS ,NONRIBOSOMAL peptide synthetases ,PEPTIDES ,PHYTOPATHOGENIC microorganisms ,TERTIARY structure ,PLANT roots - Abstract
Pyoverdines are iron-chelating siderophores employed by various pseudomonads to promote their growth in iron-limited environments, facilitating both beneficial and detrimental interactions with co-inhabiting microbes or hosts, including plants and animals. The fluorescent pseudomonads produce fluorescent pyoverdines comprised of a conserved central chromophore and a unique strain-specific peptidic side chain produced by non-ribosomal peptide synthetases. Pyoverdine Pf5 (PVD-Pf5) is produced by Pseudomonas protegens Pf-5, a species known for supporting plant growth and its involvement in plant pathogen control. To develop a means of exploring the dynamics of P. protegens activity in soil and in the rhizosphere, we selected DNA aptamers that specifically recognize PVD-Pf5 with high affinities. Two selected aptamers with only 16% identity in sequence were examined for structure and function. We found evidence that both aptamers form structures in their apo-forms and one aptamer has structural features suggesting the presence of a G-quadruplex. Although their tertiary structures are predicted to be different, both aptamers bind the target PVD-Pf5 with similar affinities and do not bind other siderophores, including the related pyoverdine, pseudobactin, produced by Pseudomonas sp. B10. One aptamer binds the pyoverdine peptide component and may also interact with the chromophore. This aptamer was integrated into a nanoporous aluminum oxide biosensor and demonstrated to successfully detect PVD-Pf5 and not to detect other siderophores that do not bind to the aptamer when evaluated in solution. This sensor provides a future opportunity to track the locations of P. protegens around plant roots and to monitor PVD-Pf5 production and movement through the soil. [ABSTRACT FROM AUTHOR]
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- 2024
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11. Evaluation of the potential food allergy risks of human lactoferrin expressed in Komagataella phaffii.
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Anaya, Yanisa, Martinez, Raysa Rosario, Goodman, Richard E., Johnson, Philip, Vajpeyi, Shashwat, Xiaoning Lu, Peterson, Ross, Weyers, Sarah M., Breen, Bella, Newsham, Kahler, Scottoline, Brian, Clark, Anthony J., and Malinczak, Carrie-Anne
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FOOD allergy ,RECOMBINANT proteins ,LACTOFERRIN ,PICHIA pastoris ,BREAST milk - Abstract
Introduction: Prior to the introduction of novel food ingredients into the food supply, safety risk assessments are required, and numerous prediction models have been developed and validated to evaluate safety. Methods: The allergenic risk potential of Helaina recombinant human lactoferrin (rhLF, Effera™), produced in Komagataella phaffii (K. phaffii) was assessed by literature search, bioinformatics sequence comparisons to known allergens, glycan allergenicity assessment, and a simulated pepsin digestion model. Results: The literature search identified no allergenic risk for Helaina rhLF, K. phaffii, or its glycans. Bioinformatics search strategies showed no significant risk for cross-reactivity or allergenicity between rhLF or the 36 residual host proteins and known human allergens. Helaina rhLF was also rapidly digested in simulated gastric fluid and its digestibility profile was comparable to human milk lactoferrin (hmLF), further demonstrating a low allergenic risk and similarity to the hmLF protein. Conclusion: Collectively, these results demonstrate a low allergenic risk potential of Helaina rhLF and do not indicate the need for further clinical testing or serum IgE binding to evaluate Helaina rhLF for risk of food allergy prior to introduction into the food supply. [ABSTRACT FROM AUTHOR]
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- 2024
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12. Transient X‐Ray Absorption Near Edge Structure Spectroscopy Using Broadband Free‐Electron Laser Pulses.
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Juranić, Pavle, Cirelli, Claudio, Mamyrbayev, Talgat, Uemura, Yohei, Vila‐Comamala, Joan, Lima, Frederico Alves, Bacellar, Camila, Johnson, Philip J. M., Prat, Eduard, Reiche, Sven, Wach, Anna, Bykova, Iuliia, Kahraman, Abdullah, Kabanova, Victoria, Milne, Christopher, and David, Christian
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OXALATES ,X-ray absorption near edge structure ,ACQUISITION of data ,SPECTROMETRY ,BANDWIDTHS ,FREE electron lasers ,ABSORPTION ,LASER pulses - Abstract
A new method for time‐resolved X‐ray absorption near edge structure (XANES) spectroscopy that enables faster data acquisition and requires smaller sample quantities for high‐quality data, thus allowing the analysis of more samples in a shorter time is introduced. The method uses large bandwidth free electron laser pulses to measure laser‐excited XANES spectra in transmission mode. A beam‐splitting grating configuration allows simultaneous measurements of the spectra of the incoming X‐ray Free Electron Laser (XFEL) pulses and transmission XANES, which is crucial for compensating the pulse‐dependent intensity and spectrum fluctuations due to the self‐amplified spontaneous emission operation. The implementation of this new methodology is applied on a liquid solution of ammonium iron(III) oxalate jet and is compared to previous results, showing great improvements in the speed of acquisition and spectral resolution, and the ability to measure a large 2‐D spectral‐time map quickly. [ABSTRACT FROM AUTHOR]
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- 2024
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13. Amodiaquine Nonspecifically Binds Double Stranded and Three‐Way Junction DNA Structures
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Slavkovic, Sladjana, primary, Shoara, Aron, additional, Kaiyum, Yunus, additional, Churcher, Zachary, additional, Liu, Tao, additional, Simine, Lena, additional, and Johnson, Philip, additional
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- 2024
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14. Vibration bending fatigue analysis of Ti‐6Al‐4V airfoil blades repaired using additive manufacturing
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Smith, Lucas, primary, Scott‐Emuakpor, Onome, additional, Gockel, Joy, additional, Celli, Dino, additional, and Johnson, Philip, additional
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- 2024
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15. Soft robotics for farm to fork: applications in agriculture & farming
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Armanini, Costanza, Junge, Kai, Johnson, Philip, Whitfield, Charles, Renda, Federico, Calisti, Marcello, Hughes, Josie, Armanini, Costanza, Junge, Kai, Johnson, Philip, Whitfield, Charles, Renda, Federico, Calisti, Marcello, and Hughes, Josie
- Abstract
Agricultural tasks and environments range from harsh field conditions with semi-structured produce or animals, through to post-processing tasks in food-processing environments. From farm to fork, the development and application of soft robotics offers a plethora of potential uses. Robust yet compliant interactions between farm produce and machines will enable new capabilities and optimize existing processes. There is also an opportunity to explore how modeling tools used in soft robotics can be applied to improve our representation and understanding of the soft and compliant structures common in agriculture. In this review, we seek to highlight the potential for soft robotics technologies within the food system, and also the unique challenges that must be addressed when developing soft robotics systems for this problem domain. We conclude with an outlook on potential directions for meaningful and sustainable impact, and also how our outlook on both soft robotics and agriculture must evolve in order to achieve the required paradigm shift.
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- 2024
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16. Accessing metal-specific orbital interactions in C–H activation with resonant inelastic X-ray scattering
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Banerjee, Ambar, Jay, Raphael, Leitner, Torsten, Wang, Ru-Pan, Harich, Jessica, Stefanuik, Robert, Coates, Michael R., Beale, Emma V., Kabanova, Victoria, Kahraman, Abdullah, Wach, Anna, Ozerov, Dmitry, Arrell, Christopher, Milne, Christopher, Johnson, Philip J. M., Cirelli, Claudio, Bacellar, Camila, Huse, Nils, Odelius, Michael, Wernet, Philippe, Banerjee, Ambar, Jay, Raphael, Leitner, Torsten, Wang, Ru-Pan, Harich, Jessica, Stefanuik, Robert, Coates, Michael R., Beale, Emma V., Kabanova, Victoria, Kahraman, Abdullah, Wach, Anna, Ozerov, Dmitry, Arrell, Christopher, Milne, Christopher, Johnson, Philip J. M., Cirelli, Claudio, Bacellar, Camila, Huse, Nils, Odelius, Michael, and Wernet, Philippe
- Abstract
Photochemically prepared transition-metal complexes are known to be effective at cleaving the strong C–H bonds of organic molecules in room temperature solutions. There is also ample theoretical evidence that the two-way, metal to ligand (MLCT) and ligand to metal (LMCT), charge-transfer between an incoming alkane C–H group and the transition metal is the decisive interaction in the C–H activation reaction. What is missing, however, are experimental methods to directly probe these interactions in order to reveal what determines reactivity of intermediates and the rate of the reaction. Here, using quantum chemical simulations we predict and propose future time-resolved valence-to-core resonant inelastic X-ray scattering (VtC-RIXS) experiments at the transition metal L-edge as a method to provide a full account of the evolution of metal–alkane interactions during transition-metal mediated C–H activation reactions. For the model system cyclopentadienyl rhodium dicarbonyl (CpRh(CO)2), we demonstrate, by simulating the VtC-RIXS signatures of key intermediates in the C–H activation pathway, how the Rh-centered valence-excited states accessible through VtC-RIXS directly reflect changes in donation and back-donation between the alkane C–H group and the transition metal as the reaction proceeds via those intermediates. We benchmark and validate our quantum chemical simulations against experimental steady-state measurements of CpRh(CO)2 and Rh(acac)(CO)2 (where acac is acetylacetonate). Our study constitutes the first step towards establishing VtC-RIXS as a new experimental observable for probing reactivity of C–H activation reactions. More generally, the study further motivates the use of time-resolved VtC-RIXS to follow the valence electronic structure evolution along photochemical, photoinitiated and photocatalytic reactions with transition metal complexes.
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- 2024
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17. The Detection of Thoracolumbar Spine Injuries in Horses with Chronic Laminitis Using a Novel Clinical-Assessment Protocol and Ultrasonographic Examination.
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Guedes, Julia R. B., Vendruscolo, Cynthia P., Tokawa, Paula K. A., Carvalho, Armando M., Johnson, Philip J., and Faleiros, Rafael R.
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LAMINITIS ,HORSES ,SPINE ,FORELIMB ,SHOW horses ,POSTURAL muscles - Abstract
Simple Summary: Laminitis is a significant cause of horse mortality and it profoundly impacts the distal locomotor apparatus, causing intense pain primarily in the thoracic limbs. Affected horses exhibit a characteristic arched back and flexed thoracolumbar spinal posture. To the authors' knowledge, there are no studies investigating the relationship between chronic laminitis and thoracolumbar spine injuries. The aim of this study was to investigate the occurrence and severity of injuries in the thoracolumbar spine of horses and the association with (n = 30) or without (n = 30) chronic laminitis. We developed a clinical-assessment method for the equine thoracolumbar spine, along with the equine Grimace Scale for pain assessment and ultrasound scans. The results indicated a significant association between chronic laminitis and thoracolumbar spinal injuries, with affected horses showing higher pain manifestations and increased injury rates based on clinical examination and ultrasound assessments. Horses with laminitis displayed a 14-times higher prevalence of relevant ultrasound injuries in the thoracolumbar spine. These findings emphasize the urgent need for further research to characterize and address these injuries, and an identification of targeted preventive and therapeutic measures to enhance the well-being of horses with chronic laminitis. Postural adaptation is a prominent feature in horses affected by laminitis. Laminitis induces intense pain, especially in the forelimbs, prompting affected horses to assume a caudally displaced trunk posture, resulting in the hyperflexion of the thoracolumbar spine. This study assessed the nature and prevalence of thoracolumbar injuries in horses with chronic laminitis compared to horses without it. Sixty horses were used (thirty laminitic and thirty non-laminitic) of different athletic purposes and ages (2–20 years). The experimental protocol entailed a single assessment of horses' thoracolumbar spines, utilizing physical examination by MACCTORE, a scoring system developed specifically for this study. Additional evaluations included the Grimace Equine Pain Scale (HGS) and ultrasound exams. Statistical tests were used to compare values (Mann–Whitney or t-test) and lesions prevalences (Fisher) between groups (p < 0.05). The results showed a higher pain manifestation (HGS and heart rate, p < 0.0001) and thoracolumbar-spine-injury levels in chronic laminitis horses, both in MACCTORE clinical examinations (11.7 ± 4.8 vs. 4.2 ± 3.3, p < 0.0001) and general ultrasonographic indices (39.6 ± 12.0 vs. 20.7 ± 7.1, p < 0.0001), including specific examination approaches for various spinal elements. Horses with laminitis presented with a 14-fold higher prevalence of ultrasound-relevant lesions in the thoracolumbar spine (CI: 4.4 to 50.6, p < 0.0001) compared to controls. These findings constitute new evidence of an association between chronic laminitis and the presence of thoracolumbar spine injuries in horses, which may be confirmed by more sophisticated study designs. [ABSTRACT FROM AUTHOR]
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- 2024
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18. Identification of a novel perifornical-hypothalamic-area-projecting serotonergic system that inhibits innate panic and conditioned fear responses
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Bernabe, Cristian S., primary, Caliman, Izabela F., additional, de Abreu, Aline R. R., additional, Molosh, Andrei I., additional, Truitt, William A., additional, Shekhar, Anantha, additional, and Johnson, Philip L., additional
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- 2024
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19. Correlation of refractive index based and THz streaking arrival time tools for a hard X-ray free-electron laser
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Błachucki, Wojciech, primary, Johnson, Philip J. M., additional, Usov, Ivan, additional, Divall, Edwin, additional, Cirelli, Claudio, additional, Knopp, Gregor, additional, Juranić, Pavle, additional, Patthey, Luc, additional, Szlachetko, Jakub, additional, Lemke, Henrik, additional, Milne, Christopher, additional, and Arrell, Christopher, additional
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- 2024
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20. Evaluation of the potential food allergy risks of recombinant human lactoferrin expressed inKomagataella phaffii
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Anaya, Yanisa, primary, Rosario Martinez, Raysa, additional, Goodman, Richard E., additional, Johnson, Philip, additional, Vajpeyi, Shashwat, additional, Lu, Xiaoning, additional, Peterson, Ross, additional, Weyers, Sarah M., additional, Breen, Bella, additional, Newsham, Kahler, additional, Scottoline, Brian, additional, Clark, Anthony, additional, and Malinczak, Carrie-Anne, additional
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- 2024
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21. Soft robotics for farm to fork: applications in agriculture & farming
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Armanini, Costanza, primary, Junge, Kai, additional, Johnson, Philip H, additional, Whitfield, Charles, additional, Renda, Federico, additional, Calisti, Marcello, additional, and Hughes, Josie, additional
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- 2024
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22. Accessing metal-specific orbital interactions in C–H activation with resonant inelastic X-ray scattering
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Banerjee, Ambar, primary, Jay, Raphael M., additional, Leitner, Torsten, additional, Wang, Ru-Pan, additional, Harich, Jessica, additional, Stefanuik, Robert, additional, Coates, Michael R., additional, Beale, Emma V., additional, Kabanova, Victoria, additional, Kahraman, Abdullah, additional, Wach, Anna, additional, Ozerov, Dmitry, additional, Arrell, Christopher, additional, Milne, Christopher, additional, Johnson, Philip J. M., additional, Cirelli, Claudio, additional, Bacellar, Camila, additional, Huse, Nils, additional, Odelius, Michael, additional, and Wernet, Philippe, additional
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- 2024
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23. Equine metabolic syndrome: part 2
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Johnson, Philip J
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Obesity, insulin dysregulation and predisposition to endocrinopathic laminitis represent the major cornerstones of equine metabolic syndrome. This article summarises new information pertaining to the predispositions and pathophysiology of equine metabolic syndrome and presents some newly emergent and effective treatments for this important and common condition.
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- 2024
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24. Serologic Detection of Hepatocellular Carcinoma: Application of Machine Learning and Implications for Diagnostic Models.
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Johnson, Philip J., Bhatti, Ehsan, Toyoda, Hidenori, and He, Shan
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HEPATOCELLULAR carcinoma , *MACHINE learning , *SERODIAGNOSIS , *LENTILS , *WEB-based user interfaces , *STATISTICAL models - Abstract
PURPOSE: The gender, age, lens culinaris agglutinin-reactive fraction of alphafetoprotein, alphafetoprotein, des-gamma-carboxyprothrombin (GALAD) score is a biomarker-based statistical model for the serologic diagnosis of hepatocellular carcinoma (HCC) that has been developed and validated using the case-control approach with a view to early detection. Performance has, however, been suboptimal in the first prospective studies which better reflect the real-world situation. In this article, we report the application of machine learning to a large, prospectively accrued, HCC surveillance data set. PATIENTS AND METHODS: Models were built on a cohort of 3,473 patients with chronic liver disease within a rigorous surveillance program between 1998 and 2014, during which 459 patients with HCC were detected. Two random forest (RF) models were trained. The first RF model uses the same variables as the original GALAD model (GALAD-RF); the second is based on routinely available clinical and laboratory features (RF-practical). For comparison, we evaluated a logistic regression GALAD model trained on this longitudinal prospective data set (termed GALAD-Ogaki). RESULTS: Models were evaluated using a repetitive cross-validation approach with the metrics averaged over 100 independent runs. As judged by area under the receiver operator curve (AUROC) and F1 score, the GALAD RF model significantly outperformed the original GALAD model. The RF-practical model also outperformed the original GALAD model in terms of both AUROC and F1 score, and both models outperformed the individual biomarkers. An online web application that implemented the GALAD-RF and RF-practical models is presented. CONCLUSION: RF-based models improve on the diagnostic performance of the original GALAD model in the setting of a standard HCC surveillance program. Further prospective validation studies are warranted using these models and could be expanded to offer prediction of risk of HCC development over defined periods of time. Machine learning is used to predict development of hepatocellular carcinoma in those with cirrhosis [ABSTRACT FROM AUTHOR]
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- 2024
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25. The adoption of robotics in pack houses for fresh produce handling.
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Mulholland, Barry J, Panesar, Pardeep S, and Johnson, Philip H
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END effectors (Robotics) ,ROBOTICS ,SOFT robotics ,INDUSTRIAL robots ,WAGE increases - Abstract
Fresh produce handling, particularly in final inspection and pack, is highly dependent on dextrous human labour. As part of a relatively low-profit margin industry, rising wage costs and labour shortages are impacting the viability of this sector and are a direct threat to global food security. Adoption of robotics is required to automate delicate handling tasks; this is a key goal for sustainable and profitable businesses that supply packed produce to consumers. This mini review considers the state of the art, as well as any developments required in robotic technology for the automation of inspection and packing of whole unprocessed fresh produce. There is a particular focus on robotic end effectors for the handling of fresh produce. We consider the role of soft robotics research in meeting hygiene and safety requirements, as well as the current limited range of end effectors for handling of highly varied and delicate produce types. Future directions are discussed based on the observation of available current technology available in research and the application to commercial practice. [ABSTRACT FROM AUTHOR]
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- 2024
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26. Mexico has a trailblazing new president. But does she have any new ideas to tackle spiralling crime?
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Johnson, Philip
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- 2024
27. The US election has put the spotlight on Haiti. Its history reveals extensive exploitation by the US -- and France.
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Johnson, Philip
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HAITIANS ,SLAVE rebellions ,NATIONAL character ,SLAVERY ,POLITICAL stability - Abstract
The article discusses the unfounded claims made by Donald Trump and JD Vance about Haitian immigrants causing crime and disorder in Springfield, Ohio. It highlights the role of the US in Haiti's problems, including the debt forced upon Haiti by the US and France. The article also explores the historical exploitation of Haiti by the US and France, including the imposition of reparations and debt, US military interventions, and support for dictators. It emphasizes the need to understand the complex history and external factors that have contributed to Haiti's current challenges. [Extracted from the article]
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- 2024
28. Disseminated pleomorphic rhabdomyosarcoma in a horse
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Carpenter, Alexis L., Townsend, Kile S., Johnson, Philip J., and Kim, Dae Y.
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An 8-y-old National Show Horse mare was presented for evaluation of pneumonia and laminitis. Harsh bronchovesicular sounds were auscultated throughout both lung fields, and the mare had signs of moderately painful laminitis. Thoracic ultrasonography revealed lung consolidation throughout the dorsal aspect of both lungs, and radiography revealed an extensive diffuse-to-patchy bronchointerstitial lung pattern. The mare’s clinical condition rapidly deteriorated, and euthanasia was elected. On postmortem examination, the lungs, omentum, spleen, liver, adrenal glands, kidneys, and femur contained 0.5–2.5-cm, firm, tan nodules. Histologically, the lungs, spleen, liver, kidneys, adrenal glands, omentum, left eye, and femur were infiltrated by bundles and nests of pleomorphic polygonal-to-spindloid cells intermixed with frequent multinucleate cells. Lymphatic vessels in the affected tissues were frequently distended with tumor emboli. Neoplastic cells were diffusely positive for vimentin, desmin, sarcomeric actin, myoblastic differentiation protein 1, and myogenin, supportive of the diagnosis of rhabdomyosarcoma (RMS), which is a rare neoplasm in horses. Cross-striations were not evident with H&E or phosphotungstic acid–hematoxylin stains. Markedly pleomorphic neoplastic cells, multinucleate cells, and lack of cross-striations suggested the subclassification of pleomorphic RMS.
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- 2024
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29. 2D-IR Spectroscopy of an AHA Labeled Photoswitchable PDZ2 Domain
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Stucki-Buchli, Brigitte, Johnson, Philip J. M., Bozovic, Olga, Zanobini, Claudio, Koziol, Klemens L., Hamm, Peter, Gulzar, Adnan, Wolf, Steffen, Buchenberg, Sebastian, and Stock, Gerhard
- Abstract
We explore the capability of the non-natural amino acid azidohomoalanine (AHA) as an IR label to sense relatively small structural changes in proteins with the help of 2D IR difference spectroscopy. To that end, we AHA-labeled an allosteric protein (the PDZ2 domain from human tyrosine-phosphatase 1E) and furthermore covalently linked it to an azobenzene-derived photoswitch as to mimic its conformational transition upon ligand binding. To determine the strengths and limitations of the AHA label, in total six mutants have been investigated with the label at sites with varying properties. Only one mutant revealed a measurable 2D IR difference signal. In contrast to the commonly observed frequency shifts that report on the degree of solvation, in this case we observe an intensitychange. To understand this spectral response, we performed classical MD simulations, evaluating local contacts of the AHA labels to water molecules and protein side chains and calculating the vibrational frequency on the basis of an electrostatic model. Although these simulations revealed in part significant and complex changes of the number of intraprotein and water contacts upon trans–cisphotoisomerization, they could not provide a clear explanation of why this one label would stick out. Subsequent quantum-chemistry calculations suggest that the response is the result of an electronic interaction involving charge transfer of the azido group with sulfonate groups from the photoswitch. To the best of our knowledge, such an effect has not been described before.
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- 2024
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30. Lower hepatocellular carcinoma surveillance in metabolic dysfunction‐associated steatotic liver disease: Impact on treatment eligibility.
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Henry‐Blake, Connor, Balachandrakumar, Vinay, Kassab, Mohamed, Devonport, Joshua, Matthews, Charmaine, Fox, James, Baggus, Elisabeth, Henney, Alexander, Stern, Nicholas, Cuthbertson, Daniel J, Palmer, Daniel, Johnson, Philip J, Hughes, David M, Hydes, Theresa J, and Cross, Timothy J S
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FATTY liver , *PROPORTIONAL hazards models , *EARLY detection of cancer , *FISHER exact test , *LIVER cancer - Abstract
Background and Aim Methods Results Conclusion This study aimed to compare the determinants and impact of hepatocellular carcinoma (HCC) surveillance rates for people with metabolic dysfunction‐associated steatotic liver disease (MASLD)
versus other chronic liver diseases.A dataset of HCC patients from a UK hospital (2007–2022) was analyzed. The Mann–WhitneyU ‐test compared continuous variables. Theχ 2 and two‐tailed Fisher exact tests compared categorical data. Regression modeling analyzed the impact of MASLD on the size and number of HCC nodules and curative treatment. The Cox proportional hazards model assessed the influence of MASLD on overall survival.A total of 176 of 687 (25.6%) HCC patients had MASLD. Fewer people with MASLD HCC were enrolled in HCC surveillance compared to non‐MASLD HCC (38 [21.6%]vs 215 [42.1%],P < 0.001). Patients with MASLD HCC were less likely to have been under secondary care (n = 57 [32.4%]vs 259 [50.7%],P < 0.001) and less likely to have cirrhosis (n = 113 [64.2%]vs 417 [81.6%],P < 0.001). MASLD was associated with a 12.3‐mm (95% confidence interval [CI] 10.8–14.0 mm) greater tumor diameter compared to people without MASLD (P = 0.002). Patients with MASLD HCC had 0.62 reduced odds (95% CI 0.43–0.91) of receiving curative treatment compared to non‐MASLD HCC (P = 0.014). Overall survival was similar for patients with MASLD HCCversus non‐MASLD HCC (hazard ratio 1.03, 95% CI 0.85–1.25,P = 0.748).Patients with MASLD are less likely to have been enrolled in HCC surveillance due to undiagnosed cirrhosis or presenting with non‐cirrhotic HCC. Patients with MASLD HCC present with larger tumors and are less likely to receive curative treatment. [ABSTRACT FROM AUTHOR]- Published
- 2024
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31. DNA aptamers for common buffer molecules: possibility of buffer interference in SELEX.
- Author
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Ding Y, Zhang Z, Kaiyum YA, Heng Y, Johnson PE, and Liu J
- Abstract
During a typical aptamer selection experiment, buffer molecules are used at the 10 to 50 mM range, whereas target molecules could be used at much lower concentrations even in low μM levels. Therefore, doubts existed regarding the potential enrichment of buffer binding aptamers, particularly for failed selections that cannot validate binding of enriched sequences. In this study, we used two common buffer molecules, Tris and HEPES, as target molecules. While we successfully isolated aptamers for Tris buffer, our attempts to generate aptamers for HEPES buffer failed. Thioflavin T (ThT) fluorescence spectroscopy showed the dissociation constant ( K
d ) of the Tris buffer aptamer to be 2.9 mM, while isothermal titration calorimetry showed a Kd of 43 μM. NMR spectroscopy also confirmed aptamer binding. Finally, we discussed the implications of this buffer selection work and recommended the use of certain buffers.- Published
- 2024
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32. Solution-based biophysical characterization of conformation change in structure-switching aptamers.
- Author
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Eisen SR, Dauphin-Ducharme P, and Johnson PE
- Subjects
- Solutions, Humans, Biophysical Phenomena, Biosensing Techniques, Aptamers, Nucleotide chemistry, Aptamers, Nucleotide metabolism, Nucleic Acid Conformation
- Abstract
Structure-switching aptamers have become ubiquitous in several applications, notably in analytical devices such as biosensors, due to their ease of supporting strong signaling. Aside from their ability to bind specifically with their respective target, this class of aptamers also undergoes a conformational rearrangement upon target recognition. While several well-studied and early-developed aptamers (e.g., cocaine, ATP, and thrombin) have been found to have this structure-switching property, the vast majority do not. As a result, it is common to try to engineer aptamers into switches. This proves challenging in part because of the difficulty in obtaining structural and functional information about aptamers. In response, we review various readily available biophysical characterization tools that are capable of assessing structure switching of aptamers. In doing so, we delve into the fundamentals of these different techniques and detail how they have been utilized in characterizing structure-switching aptamers. While each of these biophysical techniques alone has utility, their real power to demonstrate the occurrence of structural change with ligand binding is when multiple techniques are used. We hope that through a deeper understanding of these techniques, researchers will be better able to acquire biophysical information about their aptamer-ligand systems and accelerate the translation of aptamers into biosensors.
- Published
- 2024
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33. Direct nanopore RNA sequencing of umbra-like virus-infected plants reveals long non-coding RNAs, specific cleavage sites, D-RNAs, foldback RNAs, and temporal- and tissue-specific profiles.
- Author
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Johnson PZ, Needham JM, Lim NK, and Simon AE
- Abstract
The traditional view of plus (+)-strand RNA virus transcriptomes is that infected cells contain a limited variety of viral RNAs, such as full-length (+)-strand genomic RNA(s), (-)-strand replication intermediate(s), 3' co-terminal subgenomic RNA(s), and viral recombinant defective (D)-RNAs. To ascertain the full complement of viral RNAs associated with the simplest plant viruses, long-read direct RNA nanopore sequencing was used to perform transcriptomic analyses of two related umbra-like viruses: citrus yellow vein-associated virus (CY1) from citrus and CY2 from hemp. Analysis of different timepoints/tissues in CY1- and CY2-infected Nicotiana benthamiana plants and CY2-infected hemp revealed: (i) three 5' co-terminal RNAs of 281 nt, 442 nt and 671 nt, each generated by a different mechanism; (ii) D-RNA populations containing the 671 fragment at their 5'ends; (iii) many full-length genomic RNAs and D-RNAs with identical 3'end 61 nt truncations; (iv) virtually all (-)-strand reads missing 3 nt at their 3' termini; (v) (±) foldback RNAs comprising about one-third of all (-)-strand reads and (vi) a higher proportion of full-length gRNAs in roots than in leaves, suggesting that roots may be functioning as a gRNA reservoir. These findings suggest that viral transcriptomes are much more complex than previously thought., (© The Author(s) 2024. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics.)
- Published
- 2024
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34. A Technique for Difficult Intraoperative Dislocation of Hip Prosthesis in Revision Total Hip Arthroplasty.
- Author
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Johnson PK, Lapow J, Grant AR, and Lementowski P
- Abstract
There are instances where a patient's prosthetic hip is unable to be dislocated intraoperatively during a conversion or revision arthroplasty, despite scar removal and standard dislocation maneuvers. We describe a technique that involves an in situ disassociation of the femoral head component from the trunnion without the need for additional osteotomies. This maneuver may be beneficial in cases of protrusio, muscular stiffness, high soft tissue tension, arthrofibrosis, and ankylosis due to heterotopic ossification, as well as cases that involve a large femoral head or acetabular constraint. We also present a case of a 61-year-old male with a chronic prosthetic hip infection who underwent a two-stage revision surgery where this technique was utilized., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Johnson et al.)
- Published
- 2024
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35. GZMK+CD8+ T cells Target A Specific Acinar Cell Type in Sjögren's Disease.
- Author
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Pranzatelli TJF, Perez P, Ku A, Matuck B, Huynh K, Sakai S, Abed M, Jang SI, Yamada E, Dominick K, Ahmed Z, Oliver A, Wasikowski R, Easter QT, Baer AN, Pelayo E, Khavandgar Z, Kleiner DE, Magone MT, Gupta S, Lessard C, Farris AD, Burbelo PD, Martin D, Morell RJ, Zheng C, Rachmaninoff N, Maldonado-Ortiz J, Qu X, Aure M, Dezfulian MH, Lake R, Teichmann S, Barber DL, Tsoi LC, Sowalsky AG, Tyc KM, Liu J, Gudjonsson J, Byrd KM, Johnson PLF, Chiorini JA, and Warner BM
- Abstract
Sjögren's Disease (SjD) is a systemic autoimmune disease without a clear etiology or effective therapy. Utilizing unbiased single-cell and spatial transcriptomics to analyze human minor salivary glands in health and disease we developed a comprehensive understanding of the cellular landscape of healthy salivary glands and how that landscape changes in SjD patients. We identified novel seromucous acinar cell types and identified a population of PRR4+CST3+WFDC2 - seromucous acinar cells that are particularly targeted in SjD. Notably, GZMK +CD8 T cells, enriched in SjD, exhibited a cytotoxic phenotype and were physically associated with immune-engaged epithelial cells in disease. These findings shed light on the immune response's impact on transitioning acinar cells with high levels of secretion and explain the loss of this specific cell population in SjD. This study explores the complex interplay of varied cell types in the salivary glands and their role in the pathology of Sjögren's Disease.
- Published
- 2024
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36. Ecological drivers of CRISPR immune systems.
- Author
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Xiao W, Weissman JL, and Johnson PLF
- Abstract
CRISPR-Cas is the only known adaptive immune system of prokaryotes. It is a powerful defense system against mobile genetic elements such as bacteriophages. While CRISPR-Cas systems can be found throughout the prokaryotic tree of life, they are distributed unevenly across taxa and environments. Since adaptive immunity is more useful in environments where pathogens persist or reoccur, the density and/or diversity of the host/pathogen community may drive the uneven distribution of CRISPR system. We directly tested hypotheses connecting CRISPR incidence with prokaryotic density/diversity by analyzing 16S rRNA and metagenomic data from publicly available environmental sequencing projects. In terms of density, we found that CRISPR systems are significantly favored in lower abundance (less dense) taxa and disfavored in higher abundance taxa, at least in marine environments. When we extended this work to compare taxonomic diversity between samples, we found CRISPR system incidence strongly correlated with diversity in human oral environments. Together, these observations confirm that, at least in certain types of environments, the prokaryotic ecological context indeed plays a key role in selecting for CRISPR immunity., Importance: 2Microbes must constantly defend themselves against viral pathogens, and a large proportion of prokaryotes do so using the highly effective CRISPR-Cas adaptive immune system. However, many prokaryotes do not. We investigated the ecological factors behind this uneven distribution of CRISPR-Cas immune systems in natural microbial populations. We found strong patterns linking CRISPR-Cas systems to prokaryotic density within ocean environments and to prokaryotic diversity within human oral environments. Our study validates previous within-lab experimental results that suggested these factors might be important and confirms that local environment and ecological context interact to select for CRISPR immunity.
- Published
- 2024
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37. The Detection of Thoracolumbar Spine Injuries in Horses with Chronic Laminitis Using a Novel Clinical-Assessment Protocol and Ultrasonographic Examination.
- Author
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Guedes JRB, Vendruscolo CP, Tokawa PKA, Carvalho AM, Johnson PJ, and Faleiros RR
- Abstract
Postural adaptation is a prominent feature in horses affected by laminitis. Laminitis induces intense pain, especially in the forelimbs, prompting affected horses to assume a caudally displaced trunk posture, resulting in the hyperflexion of the thoracolumbar spine. This study assessed the nature and prevalence of thoracolumbar injuries in horses with chronic laminitis compared to horses without it. Sixty horses were used (thirty laminitic and thirty non-laminitic) of different athletic purposes and ages (2-20 years). The experimental protocol entailed a single assessment of horses' thoracolumbar spines, utilizing physical examination by MACCTORE, a scoring system developed specifically for this study. Additional evaluations included the Grimace Equine Pain Scale (HGS) and ultrasound exams. Statistical tests were used to compare values (Mann-Whitney or t -test) and lesions prevalences (Fisher) between groups ( p < 0.05). The results showed a higher pain manifestation (HGS and heart rate, p < 0.0001) and thoracolumbar-spine-injury levels in chronic laminitis horses, both in MACCTORE clinical examinations (11.7 ± 4.8 vs. 4.2 ± 3.3, p < 0.0001) and general ultrasonographic indices (39.6 ± 12.0 vs. 20.7 ± 7.1, p < 0.0001), including specific examination approaches for various spinal elements. Horses with laminitis presented with a 14-fold higher prevalence of ultrasound-relevant lesions in the thoracolumbar spine (CI: 4.4 to 50.6, p < 0.0001) compared to controls. These findings constitute new evidence of an association between chronic laminitis and the presence of thoracolumbar spine injuries in horses, which may be confirmed by more sophisticated study designs.
- Published
- 2024
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