bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics of Envarsus in pediatric kidney transplant recipients – phase 1 pilot conversion study
Authors: Kim Jon Jin , Lawless Laura , Marshall David , Maxted Andrew , Lunn Andrew , Mallik Meeta , Williams Alun 
Published: March 2024

AbstractIntroductionTacrolimus is the standard immunosuppressant for pediatric kidney transplants and is routinely administered twice daily (BD‐tac). Envarsus (LCP‐tac), an extended‐release formulation, is approved for adults but not for pediatric patients.MethodsWe conducted a pilot open‐label phase 1 study in stable pediatric kidney transplant recipients (age < 18 at the time of study). Our primary objective was to compare the pharmacokinetics (Pk) of LCP‐tac versus BD‐tac. We conducted two 24‐h Pk studies: pre‐conversion (BD‐tac) and 4 weeks post‐conversion to LCP‐tac. Patients were followed for 6 months, with the option to continue LCP‐tac.ResultsFive patients completed the study, with no returns to BD‐tac. Median age was 15 years (range 11–17). LCP‐tac exhibited an extended‐release profile versus the bimodal profile of BD‐tac. Time to maximum concentration was delayed (5 h vs. 1 h), and maximum concentration was lower (9.9 ng/mL vs. 14.4 ng/mL). Tacrolimus area under the curve (24 h) was comparable (141 ± 46.5 ng/mL vs. 164 ± 27.8 ng/mL). No new safety concerns arose. There were no rejection and no difference in eGFR at the study's end (1.5 mL/min/1.73 m2, range − 1.7 to 2.3 mL/min/1.73 m2). Concentration/dose ratio was higher in LCP‐tac (1.8 ± 0.64 vs. 0.8 ± 0.39). The final conversion ratio was 0.6 (BD‐tac: LCP‐tac).ConclusionOur pilot study confirms the extended‐release Pk profile and improved absorption of LCP‐tac compared to BD‐tac. A larger study is needed to further evaluate the population Pk characteristics in children.
Mitochondrial targeting improves the selectivity of singlet‐oxygen cleavable prodrugs in NMIBC treatment
Authors: Rahman Kazi Md Mahabubur , Bist Ganesh , Kumbham Soniya , Foster Barbara A. , Woo Sukyung , You Youngjae 
Published: March 2024

AbstractMitochondria play an essential role in cancer treatment by providing apoptotic signals. Hexyl aminolevulinate, an FDA‐approved diagnosis for non‐muscle invasive bladder cancer, induces the production of protoporphyrin IX (PpIX) preferentially by mitochondria in cancer cells. Photosensitizer PpIX upon illumination can release active chemotherapy drugs from singlet oxygen‐activatable prodrugs. Prodrugs placed close enough to PpIX formed in mitochondria can improve the antitumor efficiency of PpIX‐PDT. The preferred uptake of prodrugs by cancer cells and tumors can further enhance the selective damage of cancer cells over non‐cancer cells and surrounding normal tissues. Mitochondriotropic prodrugs of anticancer drugs, such as paclitaxel and SN‐38, were synthesized using rhodamine, a mitochondrial‐targeting moiety. In vitro, the mitochondrial targeting helped achieve preferential cellular uptake in cancer cells. In RT112 cells (human bladder cancer cells), intracellular prodrug concentrations were 2–3 times higher than the intracellular prodrug concentrations in BdEC cells (human bladder epithelial cells), after 2 h incubation. In an orthotopic rat bladder tumor model, mitochondria‐targeted prodrugs achieved as much as 34 times higher prodrug diffusion in the tumor area compared to the nontumor bladder area. Overall, mitochondria targeting made prodrugs more effective in targeting cancer cells and tumors over non‐tumor areas, thereby reducing nonspecific toxicity.
AnWRKY29 and AnHSP90 synergistically modulate trehalose levels in a desert shrub leaves during osmotic stress
Authors: Wang Shuyao , Hao Xin , Liu Yahui , Chen Yingying , Qu Yue , Wang Zhaoyuan , Shen Yingbai 
Published: March 2024

AbstractTrehalose, a biological macromolecule with osmotic adjustment properties, plays a crucial role during osmotic stress. As a psammophyte, Ammopiptanthus nanus relies on the accumulation of organic solutes to respond to osmotic stress. We utilized virus‐induced gene silencing technology for the first time in the desert shrub A. nanus to confirm the central regulatory role of AnWRKY29 in osmotic stress, as it controls the transcription of AnTPS11 (trehalose‐6‐phosphate synthase 11). Further investigation has shown that AnHSP90 may interact with AnWRKY29. The AnHSP90 gene is sensitive to osmotic stress, underscoring its pivotal role in orchestrating the response to such adverse conditions. By directly targeting the W‐box element within the AnTPS11 promoter, AnWRKY29 effectively enhances the transcriptional activity of AnTPS11, which is facilitated by AnHSP90. This discovery highlights the critical role of AnWRKY29 and AnHSP90 in enabling organisms to adapt to and cope effectively with osmotic stress, which can be a crucial factor in A. nanus survival and overall ecological resilience. Collectively, uncovering the molecular mechanisms underlying the osmotic responses of A. nanus is paramount for comprehending and augmenting the osmotic tolerance mechanisms of psammophyte shrub plants.
Therapeutic bronchoscopy for malignant central airway obstruction: Introduction to the EpiGETIF registry
Authors: Guibert Nicolas , Roy Pascalin , Amari Lyria , Legodec Julien , Escarguel Bruno , Fournier Clément , Wallyn Frederic , Cellerin Laurent , Lorut Christine , Usturoi Daniela , Egenod Thomas , Favrolt Nicolas , Schlossmacher Pascal , Bourinet Valerian , Loïc Perrot , Lachkar Samy , Camuset Juliette , Briault Amandine , Kessler Romain , Gut‐Gobert Christophe , Mangiapan Gilles , Carnot Nicolas , Briens Eric , Crutu Adrian , Marceau Armelle , Toublanc Bénédicte , Deslée Gaëtan , Dewolf Maxime , Dutilh Julien , Tronchetti Julie , Astoul Philippe , Vergnon Jean‐Michel , Dutau Hervé ,   the Groupe d'Endoscopie Thoracique et Interventionnel Francophone (GETIF)
Published: March 2024

AbstractBackground and ObjectiveEpiGETIF is a web‐based, multicentre clinical database created in 2019 aiming for prospective collection of data regarding therapeutic rigid bronchoscopy (TB) for malignant central airway obstruction (MCAO).MethodsPatients were enrolled into the registry from January 2019 to November 2022. Data were prospectively entered through a web‐interface, using standardized definitions for each item. The objective of this first extraction of data was to describe the population and the techniques used among the included centres to target, facilitate and encourage further studies in TB.ResultsOverall, 2118 patients from 36 centres were included. Patients were on average 63.7 years old, mostly male and smokers. Most patients had a WHO score ≤2 (70.2%) and 39.6% required preoperative oxygen support, including mechanical ventilation in 6.7%. 62.4% had an already known histologic diagnosis but only 46.3% had received any oncologic treatment. Most tumours were bronchogenic (60.6%), causing mainly intrinsic or mixed obstruction (43.3% and 41.5%, respectively). Mechanical debulking was the most frequent technique (67.3%), while laser (9.8%) and cryo‐recanalization (2.7%) use depended on local expertise. Stenting was required in 54.7%, silicone being the main type of stent used (55.3%). 96.3% of procedure results were considered at least partially successful, resulting in a mean 4.1 points decrease on the Borg scale of dyspnoea. Complications were noted in 10.9%.ConclusionThis study exposes a high volume of TB that could represent a good source of future studies given the dismal amount of data about the effects of TB in certain populations and situations.
Gilaki reverse Ezafe: The two faces of a nominal linker
Authors: Kahnemuyipour Arsalan , Shabani Mansour , Taghipour Sahar 
Published: March 2024

AbstractThis paper examines a nominal linker (known as reverse Ezafe) in the Caspian language Gilaki. It is shown that the nominal linker in Gilaki is in fact the realization of two different morphosyntactic elements with distinct properties. In doing so, we also highlight the differences between reverse Ezafe and Ezafe, found in Persian and other Iranian languages. This study has implications for the typology of nominal linkers, leading to the conclusion that superficially similar linking elements, both within a language and across languages, may in fact have different syntactic properties and as such should be analyzed as distinct phenomena.
Metastatic cutaneous myxosarcoma in an adult horse
Authors: Rabelo Andreza A. , Maranhão Renata P. A. , de Miranda Ana Luísa S. , Ocarino Natalia M. , Amaral Camila I. , Paes Paulo R. O. , Monteiro Nathalia C. C. , Fantini Priscila 
Published: March 2024

AbstractA 25‐year‐old mixed‐breed equine with separate nodular cutaneous lesions in the right thoracic limb (RTL) and right ventral abdominal region was admitted to a Veterinary Hospital in Belo Horizonte, Minas Gerais. Fine‐needle aspiration cytology was performed on the RTL lesion and superficial cervical lymph node, and the results were suggestive of a malignant neoplasm known as myxosarcoma. Due to the unfavorable prognosis, the animal was euthanized. Based on the macroscopic and microscopic findings, the diagnosis of metastatic cutaneous myxosarcoma was confirmed. Although rare, this tumor should be considered as a differential diagnosis for cutaneous neoplasms in this species.
Effects of canine influenza infection and DA2PP vaccination on the development of platelet‐associated immunoglobulins and platelet counts in dogs
Authors: Williams Maggie , Shropshire Sarah , Chornarm Nida , Brewer Melissa , Hawley Jennifer , Khorsand Matthew , Lappin Michael 
Published: March 2024

AbstractBackgroundImmune thrombocytopenia (ITP) is commonly associated with platelet‐associated immunoglobulins (PAIg). Demonstration of PAIg can help determine etiologies for thrombocytopenia. In humans, ITP and thrombocytopenia have been associated with various vaccinations and influenza infections, respectively.ObjectivesWe aimed to evaluate platelet counts and PAIg in research dogs with H3N2 and in research and client‐owned dogs routinely vaccinated for distemper, adenovirus‐2, parainfluenza, and parvovirus (DA2PP). The hypotheses were that H3N2 infection but not DA2PP vaccination would decrease platelet counts, and neither would result in the detection of PAIg.MethodsThree pilot studies. Platelet counts and PAIg, measured by direct flow cytometry as %IgG, were evaluated in eight research Beagles following experimental infection with H3N2 (experiment 1), nine research Beagles vaccinated for DA2PP (experiment 2), and thirty client‐owned dogs vaccinated for DA2PP (experiment 3). All animals were considered healthy at the start of the experiments.ResultsTransient, self‐resolving decreases in platelet counts and increases in %IgG occurred following H3N2 infection, and one dog became thrombocytopenic and positive for PAIg. Following DA2PP vaccination, %IgG increased in research and client‐owned dogs, but only one dog was considered positive for PAIg with a concurrent increase in platelet count. Mean PAIg increased from baseline in client‐owned dogs following vaccination.ConclusionsTransient PAIg and thrombocytopenia can occur following H3N2 infection, while routine vaccination for DA2PP in this group of dogs was not associated with the development of thrombocytopenia or clinically relevant formation of PAIg.
Uniaxial Quadrupole Order in a Magnet with Strong Biquadratic Exchange
Authors: Kokorina E. E. , Medvedev M. V. 
Published: March 2024

Abstract
It is shown that the temperature transition from a disordered paramagnetic state to the ground ferromagnetic state in a magnet with sufficiently strong biquadratic exchange interaction (compared to bilinear exchange) and spin S > 1 passes through an intermediate magnetically ordered phase (uniaxial quadrupole ordering). For a magnet with spin S = 3/2, a phase diagram of magnetic states in the region of large values of the biquadratic exchange is constructed in the mean-field approximation and the influence of the sequence of two phase transitions (paramagnetic state−quadrupole state and quadrupole state–ferromagnetic state) on the temperature behavior of the magnetic heat capacity and the initial magnetic susceptibility is investigated.
Light-assisted patterning of salt precipitation on photovoltaic LiNbO3 substrates
Authors: Hernández-Gutiérrez Javier , Sebastián-Vicente Carlos , García-Cabañes Angel , Carrascosa Mercedes 
Published: March 2024

AbstractThe control of salt crystallization on a surface has important implications in many technological and industrial applications. In this work, we propose and demonstrate an optoelectrical method to define and control the spatial distribution of salt crystallization on a lithium niobate photovoltaic substrate. It is based on the bulk photovoltaic effect that generates an electric field on the illuminated regions of the crystal. The salt only crystallizes on these illuminated regions of the substrate. Single salt spots or more complicated spatial patterns, defined by the light intensity spatial distribution, have been achieved. In particular, some results have been obtained using scanning/moving laser beams, i.e., “drawing” the saline patterns. The role of light exposure time and salt concentration in the aqueous solution has been studied. The method has been checked with several salts with successful results showing its general applicability. A discussion on the possible physical mechanisms behind the method and their implication for the operation of photovoltaic platforms in other applications is also included.
Abstract A006: Reckless mitotic entry as a novel chemosensitization approach for alkylating agents
Authors: Lang Fengchao , Cornwell James , Kaur Karambir , Elmogazy Omar , Zhang Wei , Zhang Meili , Song Hua , Sun Zhonghe , Wu Xiaolin , Aladjem Mirit I. , Aregger Michael , Cappell Steven , Yang Chunzhang 
Published: March 2024

Abstract
The cell cycle is tightly regulated by checkpoints, playing a vital role in controlling its progression and timing. Cancer cells exploit the G2/M checkpoint, which serves as a resistance mechanism against genotoxic anti-cancer treatments, allowing for DNA repair prior to cell division. Therefore, manipulating cell cycle timing has emerged as a potential strategy to augment the effectiveness of DNA damage-based therapies such as alkylating agents and radiation. In this study, we conducted a forward genome wide CRISPR/Cas9 screening with repeated exposure to the alkylating agent temozolomide (TMZ) to investigate the mechanisms underlying tumor cell survival under genotoxic stress. Our findings revealed that canonical DNA repair pathways, including ATM/Fanconi and mismatch repair, determine cell fate under genotoxic stress. Notably, we identified the critical role of the membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase, known as Myt1 (encoded by PKMYT1), in ensuring cell survival. Depletion of PKMYT1 led to overwhelming TMZ-induced cytotoxicity in cancer cells. Isobologram analysis demonstrated potent drug synergy between TMZ and other clinically used alkylating agents, such as carmustine, busulfan, and dacarbazine, when combined with a novel Myt1 kinase inhibitor, RP-6306. Mechanistically, inhibiting Myt1 forced G2/M-arrested cells into an unscheduled transition to the mitotic phase without complete resolution of DNA damage, as indicated by a substantial increase in γH2AX-positive cells in mitosis. Moreover, RP-6306 dramatically altered cell cycle timing, reducing the threshold time for mitotic entry. This forced entry into mitosis, along with persistent DNA damage, resulted in severe mitotic abnormalities, including unaligned and partially condensed chromosomes, lagging chromosomes, chromosome bridges, and multipolar spindles. Ultimately, these aberrations led to mitotic exit with substantial apoptosis. Importantly, preclinical animal studies demonstrated that the combination regimen involving TMZ and RP-6306 prolonged the overall survival of glioma-bearing mice. Collectively, our findings highlight the potential of targeting cell cycle timing through Myt1 inhibition as a novel strategy to enhance the efficacy of current standard cancer therapies, potentially leading to improved disease outcomes.
Citation Format: Fengchao Lang, James Cornwell, Karambir Kaur, Omar Elmogazy, Wei Zhang, Meili Zhang, Hua Song, Zhonghe Sun, Xiaolin Wu, Mirit I. Aladjem, Michael Aregger, Steven Cappell, Chunzhang Yang. Reckless mitotic entry as a novel chemosensitization approach for alkylating agents [abstract]. In: Proceedings of the AACR Special Conference on Brain Cancer; 2023 Oct 19-22; Minneapolis, Minnesota. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_1):Abstract nr A006.
Abstract A008: Disruption of SLFN5 enhances vulnerability to APR-246, a mutant p53 reactivator in glioblastoma
Authors: Perez Ricardo E. , Eckerdt Frank , Platanias Leonidas C. 
Published: March 2024

Abstract
Glioblastoma multiforme (GBM) or grade 4 IDHWT glioma is the most malignant brain tumor with a median survival of ~15 months. Current treatment options are limited to a combination of surgery, radiation, and the alkylating agent temozolomide (TMZ). However, despite this aggressive treatment regimen, patients inevitably develop recurrent tumors, which depict a high degree of resistance to DNA damage induced by TMZ and irradiation. Therefore, it is imperative to better understand cellular signals contributing to GBM tumorigenesis and therapy resistance. We have previously established potential roles for members of the protein family of schlafens (SLFNs) in GBM. SLFNs have established roles in cell differentiation, cell proliferation, immune responses, and an expanding role in cancer biology. Several human SLFNs have been linked to chemosensitivity in various cancer types. In particular, SLFN5 mRNA levels progressively increased from grade 2 to grade 4 glioma suggesting a possible therapeutic target for GBM. Therefore, in an effort to better understand the role of SLFN5 in GBM tumorigenesis, CRISPR/Cas9-mediated SLFN5 knockout glioblastoma cell lines and PDX lines were generated. Cells lacking expression of SLFN5 showed increased DNA damage signaling, as judged by elevated basal levels of the DNA damage marker γH2AX and persistent phosphorylation of Chk2. Gene ontology analysis indicated increased expression of p53 pathway components in SLFN5 knockout cells. In GBM, p53 activity is commonly deregulated due to high mutations in the p53 pathway. In line with this, SLFN5 knockout cells depicted increased sensitivity to the mutant p53 reactivator APR-246 correlating with p53 mutational status. APR-246 induced PARP cleavage in SLFN5 knockout cells was rescued by the ROS scavenger N-acetyl-D-cysteine (NAC). Our results suggest increased DNA damage signaling in SLFN5 deficient cells. Furthermore, mutant p53 reactivator APR-246 induced apoptosis is dependent on ROS signaling. In summary, we provide evidence for a protective role of SLFN5 to limit DNA damage and ROS signaling in GBM.
Citation Format: Ricardo E. Perez, Frank Eckerdt, Leonidas C. Platanias. Disruption of SLFN5 enhances vulnerability to APR-246, a mutant p53 reactivator in glioblastoma [abstract]. In: Proceedings of the AACR Special Conference on Brain Cancer; 2023 Oct 19-22; Minneapolis, Minnesota. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_1):Abstract nr A008.
Abstract A020: Neural stem cells expressing PTEN-L suppress glioblastoma invasion in vivo
Authors: Lorimer Ian A. , Lui Margarita , Lavictoire Sylvie J. , Coulombe Josee 
Published: March 2024

Abstract
Purpose: The purpose of this study is to evaluate the therapeutic potential of neural stem cells expressing PTEN-L (a variant of the tumor suppressor PTEN that can transfer between cells) in preclinical glioblastoma models. Experimental procedures: Human neural stem cells derived by direct reprogramming of peripheral blood erythroblasts were used. Using lentiviral transduction, these were engineered for doxycycline-inducible expression of a modified version of PTEN-L with optimized expression and enhanced cell-to-cell transfer properties. Expression of PTEN-L was assayed by Western blot analysis. These engineered neural stem cells were evaluated in an orthotopic mouse xenograft model in which human glioblastoma cells show extensive invasion into the uninjected hemisphere. Neural stem cells and glioblastoma cells were co-injected and mice were then randomized to chow with or without doxycycline. Mice were evaluated for overall survival and for invasion of glioblastoma cells into the uninjected hemisphere. Results: When injected intracerebrally into immunocompromised mice, peripheral blood-derived neural stem cells persisted for over four months and showed an ability to spontaneously migrate to sites distant from the injection site. When co-injected with human glioblastoma cells from patients, the neural stem cells co-migrated with glioblastoma cells along the corpus callosum and to distant sites. Peripheral blood-derived neural stem cells transduced with lentiviral vectors for doxycycline-inducible PTEN-L efficiently secreted PTEN-L. In the orthotopic mouse xenograft glioblastoma model, expression of PTEN-L by neural stem cells did not significantly improve survival in mice (log rank P = 0.5) but did significantly repress glioblastoma cell invasion into the uninjected hemisphere (two-tailed t-test P = 0.02). Conclusions. Peripheral blood-derived neural stem cells show good persistence and migrate with human glioblastoma cells in vivo. They can be engineered to efficiently secret functional PTEN-L. Peripheral blood-derived neural stem cells expressing PTEN-L do not increase survival in the one patient model tested but do repress invasion. This initial evidence for bioactivity supports further studies evaluating the ability of neural stem cells expressing PTEN-L to sensitize glioblastoma to therapeutics for which PTEN loss has been implicated in resistance.
Citation Format: Ian A. Lorimer, Margarita Lui, Sylvie J. Lavictoire, Josee Coulombe. Neural stem cells expressing PTEN-L suppress glioblastoma invasion in vivo [abstract]. In: Proceedings of the AACR Special Conference on Brain Cancer; 2023 Oct 19-22; Minneapolis, Minnesota. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_1):Abstract nr A020.