bluuebunny/crossref_metadata_2025 huggingface dataset:
Study of light deflection and shadow in the Rindler-like Schwarzschild solution
Authors: Xu Zhixin , Wang Zimo , Gu Jinqiang , He Xiaoling , Babar Rimsha , Ali Riasat
Published: September 2024

In this paper, we calculate the deflection angle in the non-plasma medium by expanding the Keeton–Petters approach. We use analysis to determine how non-magnetic plasma affects the shadow of a Schwarzschild–Rindler black hole. We only consider the spherically symmetric case in which the shadow is circular. It is assumed that the plasma is independent of pressure and magnetization. From a specified spherically symmetric spacetime, we compute the results for a spherically symmetric plasma density. Our main purpose is to derive analytically a formula for the orbital radius of the shadow. Due to the diffusive nature of plasma, the shadow’s radius is influenced by the frequency of the photons. The impacts of the non-magnetic plasma are important in radio establishment. We determine that the non-magnetic plasma incorporates a decreasing impact on the shadow size for a distant observer from the Schwarzschild–Rindler black hole. Moreover, we graphically analyze the impacts of different parameters on the shadow of the corresponding black hole.
Gravitational lensing in holonomy corrected spherically symmetric black holes with phantom global monopoles
Authors: Ahmed Faizuddin
Published: September 2024

In this paper, we address a theoretical investigation of the gravitational lensing phenomenon within the space-time framework of a holonomy-corrected spherically symmetric black hole (BH), incorporating both ordinary and phantom global monopoles. Our focus lies on the analysis of null geodesics within this BH background, examining the influence of ordinary and phantom global monopoles on the effective potential of null geodesics of the system. Afterwards, we derive analytical expressions for the deflection angle of photon light, considering weak field limit. The obtain expressions are presented up to the second order of the Loop Quantum Gravity parameter, enabling a thorough examination of the impact of ordinary and phantom global monopoles on the deflection angle.
Diameter bound for compact h-almost Ricci solitons
Authors: Faraji Hamed , Azami Shahroud
Published: September 2024

In this paper, we will focus on the structure of [Formula: see text]-almost Ricci solitons, investigate some lower bounds for the diameter of a compact gradient [Formula: see text]-almost Ricci soliton and will obtain an upper diameter bound for [Formula: see text]-almost Ricci solitons under certain conditions.
Majority rule on median semilattices
Authors: Högnäs Ulf , Powers Robert C.
Published: September 2024

In (2008), McMorris and Powers [A characterization of majority rule, J. Classif. 25 (2008) 153–158] proved that a hierarchical version of majority rule is the only consensus function satisfying restricted decisive neutrality, symmetry, monotonicity, and is biprofile nontrivial. We show that this result can be extended to any finite median semilattice [Formula: see text] such that [Formula: see text] is not a lattice, the height of [Formula: see text] is greater than one, [Formula: see text] contains at least two atoms, and [Formula: see text] satisfies a condition we call special.
A Survey on Deep Learning for Design and Generation of Virtual Architecture
Authors: Wang Anqi , Dong Jiahua , Lee Lik-Hang , Shen Jiachuan , Hui Pan
Published: September 2024

Three-dimensional (3D) shape generation techniques leveraging deep learning have garnered significant interest from both computer vision and architectural design communities, promising to enrich the content in the virtual environment. However, research on virtual architectural design remains limited, particularly regarding designer-AI collaboration and deep learning-assisted design. In our survey, we reviewed 149 related articles (81.2% of articles published between 2019 and 2023) covering architectural design, 3D shape techniques, and virtual environments. Through scrutinizing the literature, we first identify the principles of virtual architecture and illuminate its current production challenges, including datasets, multimodality, design intuition, and generative frameworks. We then introduce the latest approaches to designing and generating virtual buildings leveraging 3D shape generation and summarize four characteristics of various approaches to virtual architecture. Based on our analysis, we expound on four research agendas, including agency, communication, user consideration, and integrating tools. Additionally, we highlight four important enablers of ubiquitous interaction with immersive systems in deep learning-assisted architectural generation. Our work contributes to fostering understanding between designers and deep learning techniques, broadening access to designer-AI collaboration. We advocate for interdisciplinary efforts to address this timely research topic, facilitating content designing and generation in the virtual environment.
Hans Berger (1873–1941): the German psychiatrist who recorded the first electrical brain signal in humans 100 years ago
Authors: Vergani Alberto Arturo
Published: September 2024

In 1924, at the University Hospital in Jena, Hans Berger first recorded human brain electrical signals, revolutionizing clinical neurophysiology and neurotechnology. He developed the electroencephalogram (EEG) and identified alpha waves in the human scalp. Although initially met with skepticism, his work was later recognized as fundamental. Berger’s perseverance and conviction in his research serve as an inspiring example of dedication for students and scientists in neuroscience.
Characterization and Optimization of Coal‐Biomass Blends for Syngas Production as Alternative Transport Fuel Sources for Two‐Stroke Internal Combustion Engines in Tricycles‐Tuk Tuks in Kenya
Authors: Kariuki Benson , Njogu Paul , Kamau Joseph , Kinyua Robert
Published: September 2024

Conventional fuel sources, such as fossil fuels, have become unaffordable for the low end of the economy and thus the need for sustainable alternatives. Gasification of coal and biomass is considered as an alternative source for small‐sized engines, such as tricycles in Kenya. Mui basin coal is a low‐quality coal, available in Kenya, and blending with selected biomass (rice husks, Prosopis juliflora, and Hyphaene compressa) presents a new source of alternative transport fuel through cogasification and upgrading. The selected biomass samples were collected, air‐dried, and crushed to 60 μm and subjected to calorific determination, proximate, and ultimate analysis. Blending was done at various ratios weight by weight, while thermochemical determinations were conducted using the American Society for Testing and Materials (ASTM). The fixed carbon content was reported as 29.3 ± 5.51% for Mui basin coal, 21.1 ± 1.55% for rice husk, and 31.0 ± 1.00% for H. compressa. Blending was found to improve the hydrogen:carbon ratio with an average rate of 0.12 and decreased the sulphur and nitrogen content, leading to low emissions. The study revealed that calorific values of the fuel sources were as follows: Mui basin coal, 20.41 ± 0.15 MJ/kg; P. juliflora, 18.68 ± 0.17 MJ/kg; and H. compressa, 18.69 ± 0.00 MJ/kg, while rice husks had 12.95 ± 0.1 MJ/kg. Blending was also found to improve calorific values by average values of 0.4 MJ/kg for P. juliflora, 1.3 MJ/kg for H. compressa, and 2.28 MJ/kg for rice husk. The moisture content was reduced by 1–2% for all fuel sources; ash content was reduced by 33%, while the volatile matter was increased by 11% for P. juliflora, 7% for H compressa, and 0.2% for rice husks. The optimal blend of ratio 1 : 1 when cogasified produced syngas, which was upgraded through cleaning and cooling. The upgraded syngas had a moderate ratio of hydrogen to carbon monoxide with the right modification and retrofitting; it can be applied in internal combustion engines of tricycles‐“tuk tuks.” The study reveals that the optimal blending ratio of 1 : 1 for coal:biomass reduces the pollution ash content, increases calorific values, and enhances syngas fuel properties to moderate ratio.
Association between Genetic Admixture and Morphological Patterns in a Hybrid Zone between the Two Iberian Vipers, Vipera aspis and V. latastei
Authors: Freitas Inês , Velo-Antón Guillermo , Kaliontzopoulou Antigoni , Zuazo Óscar , Martínez-Freiría Fernando
Published: September 2024

Understanding how hybridization influences the morphology and fitness of hybrids is essential for studying adaptive evolution and ecological speciation. Secondary contact zones, where separately evolving populations meet and hybridize, offer valuable insights into the evolutionary processes driving speciation and provide an excellent system to address these questions. In this study, we investigate patterns of morphological and genetic variation of two congeneric viper species, Vipera aspis and V. latastei, across a contact zone in northern Spain (Oja‐Tirón), where vipers with mixed morphology are often detected, but genetic studies addressing hybridization and relating patterns of genetic and morphological admixture are lacking. Using nine morphological traits (scalation and colouration) and 18 microsatellite markers, we (1) estimated the extent of hybridization, (2) morphologically characterized parental species and hybrids, and (3) evaluated the correlation between patterns of genetic and morphological admixture. Analyses revealed a bimodal hybrid zone with high rate of hybridization (22%) and prevalence of late‐generation hybrids (F2 and backcrosses). Morphological analyses differentiated the two parental species, and a positive correlation (r = 0.95) was found between morphological and genetic patterns. The hybrid group displayed on average an intermediate morphology between the parentals, yet morphologically intermediate hybrids were rare in our dataset. Instead, most hybrids resembled the parental species with whom they share most of the genetic background. Notably, the hybrid group exhibited greater morphological variation than the parental groups. Traits with adaptative value, such as ventral scales and dorsal marks, showed significant differences between hybrids and the two parental species. Introgression of these traits may confer ecological advantages to hybrids, enhancing local adaptation. Overall, this study reveals a positive correlation between patterns of morphological and genetic variation across a hybrid zone and provides insights into the phenotypic consequences of hybridization on these viper species.
A Retrospective Investigation of Abortion Storm in Abergele Goats, Waghimira Zone, Amhara Region, Ethiopia
Authors: Bahiru Adane , Assefa Ayalew , Alemu Gemeda Biruk , Desta Hiwot , Tibebu Abebe , Sahle Abebe , Wieland Barbara
Published: September 2024

A retrospective study was conducted in Abergele and Ziquala districts in Ethiopia to investigate the occurrence, impact, and potential risk factors for abortion in small ruminants linked to a regional abortion storm. Affected (case) and nonaffected (control) villages were compared to assess infectious and noninfectious risk factors causing abortions. A case village was defined as a village with abortion seen in all households enrolled in the study, while a control village is characterized by presence of abortion in two and fewer households. A questionnaire survey, focus group discussions, and serological examinations were used to assess the differences in the abortion rate between the case and control villages. The Rose Bengal Plate Test for Brucellosis, Toxoplasma gondii Antibody Test Kit for Toxoplasma gondii, and ELISA for Chlamydophila abortus and Coxiella burnetii were used to detect antibodies. Per village 15 household flocks were selected. In the case villages, all flocks were affected by abortion (a mean abortion of 13 animals in Abergele and 9 in Ziquala). In contrast, only three households reported abortions in the control villages. A total of 176 blood samples were collected from the case and control villages for further laboratory diagnosis of possible causes of abortion. Of the examined flocks, 17%, 10.2%, and 2.8% were positive for Coxiella burnetii, Toxoplasma gondii, and Chlamydophila abortus, respectively. However, antibodies against Brucella melitensis were not detected. While the seroprevalence was greater for some infectious agents of abortion, there was no significant difference between the case and control villages. It is clear that the abortion problem in the study villages is complex and likely due to a mix of poor husbandry practices and the presence of infectious diseases. To better understand the underlying causes of abortion, there is a need to conduct a longitudinal study involving testing for more pathogens at the household level combined with reliable data on husbandry practices.
Use of a Nasal Cannula as a Preoxygenation Adjunct: A Randomized Crossover Study
Authors: Joel Murphy , Podder Suvajit , Nagesh Savan Kumar , Aithal Ramyatha , Devalla Aditya R. , Mathew Shaji
Published: September 2024

Background. Preoxygenation prior to induction of general anesthesia is intended to increase the oxygen reserve in the lungs. This technique delays the onset of hypoxemia during the placement of the tracheal tube. Objective. To observe the benefits of oxygen through nasal cannula when used as an adjunct during preoxygenation. Methods. We enrolled 30 healthy volunteers and conducted a sequence of six preoxygenation tests. These included 3‐minute tidal volume breathing and 8 vital capacity breaths, with and without oxygen flowing through the nasal cannula as an adjunct. Subjects were kept at a supine position with a face mask on their faces. Their baseline vitals were measured and end‐tidal O2 (ETO2) was recorded at the end of each test. The comfort of each technique was also assessed. Results. When comparing the efficacy of the two preoxygenation methods, we found that the addition of oxygen through the nasal cannula improved the efficacy of preoxygenation with both the 3‐minute tidal volume breathing method and the 8 vital capacity method (p < 0.001). The three‐minute tidal volume breathing technique had higher end‐tidal oxygen when compared to the eight vital capacity breaths. Conclusions. The administration of oxygen through a nasal cannula during preoxygenation improves the efficacy of preoxygenation in healthy volunteers. Tidal volume breathing for three minutes achieves a higher end‐tidal oxygen concentration compared to eight vital capacity breaths over one minute.
Figure S4 from A Pan-Cancer Patient-Derived Xenograft Histology Image Repository with Genomic and Pathologic Annotations Enables Deep Learning Analysis
Authors: White Brian S. , Woo Xing Yi , Koc Soner , Sheridan Todd , Neuhauser Steven B. , Wang Shidan , Evrard Yvonne A. , Chen Li , Foroughi pour Ali , Landua John D. , Mashl R. Jay , Davies Sherri R. , Fang Bingliang , Raso Maria Gabriela , Evans Kurt W. , Bailey Matthew H. , Chen Yeqing , Xiao Min , Rubinstein Jill C. , Sanderson Brian J. , Lloyd Michael W. , Domanskyi Sergii , Dobrolecki Lacey E. , Fujita Maihi , Fujimoto Junya , Xiao Guanghua , Fields Ryan C. , Mudd Jacqueline L. , Xu Xiaowei , Hollingshead Melinda G. , Jiwani Shahanawaz , Acevedo Saul , Davis-Dusenbery Brandi N. , Robinson Peter N. , Moscow Jeffrey A. , Doroshow James H. , Mitsiades Nicholas , Kaochar Salma , Pan Chong-xian , Carvajal-Carmona Luis G. , Welm Alana L. , Welm Bryan E. , Govindan Ramaswamy , Li Shunqiang , Davies Michael A. , Roth Jack A. , Meric-Bernstam Funda , Xie Yang , Herlyn Meenhard , Ding Li , Lewis Michael T. , Bult Carol J. , Dean Dennis A. , Chuang Jeffrey H.
Published: September 2024

Figure S4
Abstract A001: PAX3-FOXO1-induced transcriptional dysregulation in rhabdomyosarcoma
Authors: Stevens Bradley T. , Zhang Yang , Larsen Randolph K. , Adkins Grace E. , Hopkins Jack D. , Kimbrough Darden W. , Garcia Matthew R. , Hatley Mark E. , Abraham Brian J.
Published: September 2024

The survival rate for high-risk rhabdomyosarcoma (RMS) has not increased above 20% in the last thirty years. This insufficiency persists despite thorough molecular characterization of existing models and patient tumors, which has demonstrated that the most challenging RMS tumors harbor chromosomal translocations generating PAX3-FOXO1 (P3F) or PAX7-FOXO1 (P7F) oncofusion transcription factors. The presence of P3/7F largely explains the alveolar subtype of RMS. However, the molecular mechanisms by which P3/7F drives tumor onset and the extent to which they are required after establishment of RMS remain unclear. In recent work, we challenged the dogma that fusion-positive RMS arises from incompletely differentiated muscle cells by demonstrating that P3F-bearing endothelial precursors form RMS tumors ex vivo and in vivo. This observation proposes an explanation for why RMS is observed throughout the body including in sites devoid of skeletal muscle. Here, we describe a novel constructionist model of RMS in which the P3F protein is added to induced pluripotent stem cell-derived endothelial precursors. The inducible alveolar rhabdomyosarcoma (iARMS) system faithfully recapitulates tumor-relevant aspects of RMS biology, including histology, tumor-formation, and the upregulation of signature expression programs. P3F expression during endothelial-directed differentiation blocked endothelial maturation and reprogrammed cell identity toward skeletal muscle-like cells that form ARMS tumors in mice. The iARMS system reproducibly generates RMS over a 15-day timecourse, providing a unique model to examine gene-regulatory dynamics induced by P3F during RMS transformation. In addition to the expected upregulation of hallmark RMS factors, including MYOD1 and MYF6, we observed a cadre of additional transcription factor proteins that were induced and may contribute to transformation, as well as signature endothelial genes that became downregulated. P3F activated a set of enhancers that drove these expression patterns. P3F induced specific genetic dependencies in iARMS cells as observed in knockout screens. Our results define the fundamental cell identity changes underpinning P3F-induced transformation into FP-RMS and nominate collaborative transcription and non-transcription proteins that might be vulnerable to therapeutic attack.

Citation Format: Bradley T. Stevens, Yang Zhang, Randolph K. Larsen, Grace E. Adkins, Jack D. Hopkins, Darden W. Kimbrough, Matthew R. Garcia, Mark E. Hatley, Brian J. Abraham. PAX3-FOXO1-induced transcriptional dysregulation in rhabdomyosarcoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr A001.
Abstract A007 DNA damage response deficiency enhances neuroblastoma progression and sensitivity to combination PARP and ATR inhibition
Authors: Hayes Madeline N. , Cohen-Gogo Sarah , Kee Lynn , Layeghifard Mehdi , Valencia-Sama Ivette , Rajaselvam Anisha , Kaplan David , Villani Anita , Shlien Adam , Morgenstern Daniel A. , Irwin Meredith S
Published: September 2024

Background: Significant progress has been made in identifying mutations and defining biological heterogeneity in neuroblastoma (NB) using high-throughput sequencing approaches. However, functional roles for many specific genetic alterations in NB initiation, growth, and metastasis remain to be fully defined. Pathogenic and/or likely pathogenic (P/LP) alterations in genes involved in DNA Damage Response (DDR) pathways were identified in approximately 30% of patients enrolled in the SickKids Cancer Sequencing Program (KiCS). Despite being well studied in many adult cancers, roles for DDR disruption and potential therapeutic implications remains poorly understood for NB and other pediatric solid tumors. Aims: We aimed to define roles for DDR-deficiency in NB progression and assess the therapeutic potential of targeted agents using patient-specific DDR loss-of-function NB models. Methods: We incorporated loss-of-function mutations in atm, brca2, palb2, and bard1 into an established zebrafish MYCN-driven model of human NB and characterized tumor progression, transcriptional signatures, and response to candidate therapeutics in vivo. Human cell lines with DDR protein knock-down were used to assess candidate drug combinations in vitro. Results: Mutations in DDR genes were found to enhance tumor penetrance and metastasis in MYCN-driven zebrafish NB, and resulted in upregulation of proliferation, cell cycle checkpoint, and DNA damage repair transcriptional signatures. Zebrafish DDR-deficient NB and human NB cells with DDR protein knock-down were sensitive to the poly(ADP-ribose)-polymerase (PARP) inhibitor olaparib, and this effect was further enhanced by inhibition of the ataxia telangiectasia and rad3 related (ATR) kinase. Conclusions: Our data supports an in vivo functional role for DDR-deficiency in NB, as well as potential molecular vulnerabilities. Pre-clinical assessments in vitro and in vivo suggest therapeutic potential for combination PARP + ATR inhibition in NB patients with alterations in DDR genes.

Citation Format: Madeline N. Hayes, Sarah Cohen-Gogo, Lynn Kee, Mehdi Layeghifard, Ivette Valencia-Sama, Anisha Rajaselvam, David Kaplan, Anita Villani, Adam Shlien, Daniel A. Morgenstern, Meredith S Irwin. DNA damage response deficiency enhances neuroblastoma progression and sensitivity to combination PARP and ATR inhibition [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr A007.
Abstract A028 Unraveling the complex interplay of genetic, environmental, and lifestyle factors in cancer predisposition: A comprehensive review and analysis
Authors: David Peter Oloche O.
Published: September 2024

Cancer Predisposition is a complex and multifaceted topic that continues to intrigue researchers and scientists for decades. This thesis delves into the intricate web of factors that contribute to an individual's predisposition to cancer, aiming to unravel the mysteries surrounding this phenomenon. Through a comprehensive review of existing literature and cutting-edge research findings, the paper explores the genetic, environmental, and lifestyle factors that play a crucial role in predisposing individuals to cancer. By examining the interplay between genetic mutations, familial history, and environmental exposures, this study sheds light on the intricate mechanisms underlying cancer predisposition. Furthermore, the thesis investigates the role of epigenetic modifications, immune system dysregulation, and metabolic abnormalities in shaping an individual's susceptibility to cancer. The intricate interactions between these factors and their collective impact on cancer risk are analyzed, providing valuable insights into the underlying causes of cancer predisposition. By synthesizing the latest research findings in the field, this thesis offers a comprehensive overview of the complex nature of cancer predisposition and its multifactorial etiology. Ultimately, this study aims to contribute to our understanding of the intricate interplay between genetics, environment, and lifestyle in shaping an individual's susceptibility to cancer, paving the way for targeted prevention and personalized treatment strategies in the fight against this devastating disease.

Citation Format: Peter Oloche O. David. Unraveling the complex interplay of genetic, environmental, and lifestyle factors in cancer predisposition: A comprehensive review and analysis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr A028.
Abstract B020: Improved outcome for patients with alternative lengthening of telomeres (ALT) neuroblastoma randomized to tandem myeloablative therapy on COG ANBL0532
Authors: Koneru Balakrishna , Burrow Trevor , McCoy Kristyn , Nance Jonas , Naranjo Arlene , Zhang Fan F. , Irwin Meredith S. , Park Julie R. , Reynolds C. Patrick
Published: September 2024

Background: Overall survival (OS) of high-risk neuroblastoma (HRNB) patients with alternative lengthening of telomeres (ALT) tumors (∼23% of patients) is low. Event-free survival (EFS) of HRNB patients in COG ANBL0532 was higher for tandem relative to single ASCT.We sought to determine if ALT HRNB patients on ANBL0532 benefited from tandem ASCT. Methods:We assessed telomere maintenance mechanisms (TMM), defined as per Cancer Res 80:2663, 2020, in 204 primary tumors from ANBL0532 patients as TERT+ (high TERT mRNA), ALT (positive for telomeric DNA C-circle assay) or ultrabright telomere foci (UTF), or no TMM. Due to non-proportional hazards, survival comparisons used the Improved Two-Stage Procedure (J Stat Comput Simul. 2017; 87:1877). Results: TMM status was: ALT n=48 (23.5%), TERT+ n=140 (68.6%), TMM negative n=16 (7.8%). Patients with TERT+ tumors more frequently progressed early, but 8-year OS was superior for TERT+ compared to ALT (58.1±4.6% vs 41.6±8.2%; p=0.0007), while 8-year OS for TMM negative was 67.7±12.2%. The 8-year OS for TERT+ patients randomized to single (n=67) vs tandem (n=59) ASCT was 56.9±6.7% vs 71.8±6.5% (p=0.32) and for ALT patients randomized to single (n=20) vs tandem (n=19) ASCT was 26.9±11.5% vs 61.1±13.5% (p=0.011).For patients on ANBL0532 who received dinutuximab post-consolidation therapy, the 8-year OS for TERT+ patients who underwent single (n=52) vs tandem (n=43) ASCT was 53.5±7.6% vs 75.8±7.8% (p=0.10) while for ALT patients who underwent single (n=13) vs tandem (n=10) ASCT it was 23.1±14.3% vs 77.8±16.4% (p=0.022). Conclusions:As previously reported, patients with ALT HRNB have inferior OS relative to TERT+ HRNB.TMM negative HRNB patients had apparently higher OS than ALT or TERT+ but small numbers preclude formal analyses. OS was significantly improved in ALT HRNB by tandem ASCT.These data support use of tandem myeloablative therapy for patients with ALT neuroblastoma until effective targeted therapies become available.

Citation Format: Balakrishna Koneru, Trevor Burrow, Kristyn McCoy, Jonas Nance, Arlene Naranjo, Fan F. Zhang, Meredith S. Irwin, Julie R. Park, C. Patrick Reynolds. Improved outcome for patients with alternative lengthening of telomeres (ALT) neuroblastoma randomized to tandem myeloablative therapy on COG ANBL0532 [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr B020.
Abstract B029: Studies in human bone cell co-cultures reveal a potential mechanism underlying bone fractures in children treated with entrectinib and suggest a positive association with vitamin D
Authors: Ehnert Sabrina , Schulz Kevin A. , Cardenas Alison K. , Meneses-Lorente Georgina , Roth Adrian , Fürst-Recktenwald Sabine
Published: September 2024

Introduction: Entrectinib, a NTRK, ROS1 and ALK inhibitor, approved in the US for adult patients with ROS1-positive metastatic non-small cell lung cancer and adult and pediatric patients older than 1 month of age with solid tumors that have a NTRK gene fusion, has been associated with the occurrence of bone fractures, particularly in pediatric patients. These fractures might be caused by an inhibition of signaling pathways relevant for bone development in children. Methods: To investigate the mechanism of the observed effect we used a suite of human bone cells representing both juvenile and adult bone physiology. These models were treated with Entrectinib and its major metabolite M5. Molecular as well as functional readouts were assessed to reveal the pathomechanism of the observed clinical findings. Results: Data showed, that Entrectinib induced a reduction of cellular markers of osteoblastic activity and a reduced formation of mineralized matrix. Conversely, Entrectinib had stimulating effects on osteoclast function indicative of bone resorption. 3D osteoblast-osteoclast cultures revealed decreased stiffness after Entrectinib treatment, confirming the cell signaling data. These findings were particularly pronounced in the absence of 17β-estradiol, characteristic for juvenile bone. Finally, pre-treatment with Vitamin D led to partially restored osteoblast function in vitro, while osteoclast function was suppressed. Conclusions: These experiments support the suspected on-target effect of Entrectinib underlying increased fractures in children with developing bone, offering potential mitigation strategies once these observations have been confirmed with clinical data.

Citation Format: Sabrina Ehnert, Kevin A. Schulz, Alison K. Cardenas, Georgina Meneses-Lorente, Adrian Roth, Sabine Fürst-Recktenwald. Studies in human bone cell co-cultures reveal a potential mechanism underlying bone fractures in children treated with entrectinib and suggest a positive association with vitamin D [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr B029.
Abstract IA016: Mapping microglia – tumor crosstalk in pediatric brain cancer
Authors: Ginhoux Florent , Pasqualini Claudia
Published: September 2024

The management of diffuse midline gliomas (DMG) is one of the greatest challenges in the field of pediatric oncology. Available treatments do not improve the poor survival rates, and preclinical research is struggling to find new targets that could have the potential to revolutionize the therapeutic approach. In most of the current preclinical tools, microglia and macrophages are not taken into account, despite being the most abundant immune players in the brain tumor microenvironment. To address this issue, we established neural organoids and macrophages (iMacs) from induced pluripotent stem cells (iPSC) derived from pediatric patients treated for DMG ("autologous immuno-organoids"). We have reprogrammed fibroblasts into iPSC from 9 children with DMG and generated autologous immuno-organoids for 4 of them. These "avatars" provide a unique preclinical model to which tumor cells from the same patient can be added, enabling us to better understand the crosstalk between the tumor and its immunological microenvironment, and to evaluate new immunotherapies. In particular, we show here that iMacs decrease tumor proliferation and tumor cell-invasion capability in neural organoids, with such effect reduced upon iMac depletion using CSF1R inhibitor treatment. Genes/signaling pathways identified by multi-omics analysis and validated at proteomic level show a reciprocal reprogramming of tumor cells and iMacs over time. Altogther, our approach reveals an unique tumor macrophage crosstalk that will be targeted by tailored immunotherapies or gene modification to validate their impact on tumor progression.

Citation Format: Florent Ginhoux, Claudia Pasqualini. Mapping microglia – tumor crosstalk in pediatric brain cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr IA016.
Abstract PR007: Persistent poverty is associated with risk of early mortality among children with cancer: An analysis of SEER data
Authors: Hymel Emma , Kabayundo Josiane , Napit Krishtee , Watanabe-Galloway Shinobu
Published: September 2024

Objectives: Social determinants of health are understudied in the context of pediatric cancer. Persistent poverty, a measure developed by the National Cancer Institute and the US Department of Agriculture’s Economic Research Service, is defined as having 20% or more of an area’s population having lived below the poverty level for a period of about 30 years. The effect of persistent poverty on pediatric cancer outcomes is not well understood. Methods: This population-based longitudinal study uses data from the Surveillance, Epidemiology, and End Results (SEER)-22 registries Incidence Data with Census Tract Attributes Database. All primary cases of malignant cancer diagnosed among children aged 0-19 at diagnosis from 2006-2020 were included. Early mortality was defined as death within three months of diagnosis. Cox proportional hazards models were used to compute crude and adjusted hazard rations (aHRs) for the association between persistent poverty and early mortality. Based on a directed acyclic graph, models were also adjusted for age, sex, race/ethnicity, cancer type, and rurality (defined using Rural Urban Commuting Area codes). Results: The study included 97,132 children; 12.63% resided in a persistent poverty census tract at diagnosis and 1.66% died within three months of diagnosis. In the adjusted model, living in a persistent poverty census tract was associated with a higher risk of early mortality (aHR=1.26, 95% CI: 1.10-1.45). Additionally, a higher risk of early mortality was observed among Non-Hispanic Black (aHR=1.44, 95% CI: 1.23-1.70), Non-Hispanic Asian and Pacific Islander (aHR=1.39, 95% CI: 1.15-1.68), and Hispanic children (aHR=1.33, 95% CI: 1.18-1.49) compared to Non-Hispanic White children. Children residing in rural areas also had a higher risk of death compared to children in urban areas (aHR=1.29, 95% CI: 1.11-1.50). In sensitivity analyses looking at the effect of persistent poverty on risk of death within one month of diagnosis, a similar effect size was observed (aHR=1.26, 95% CI: 1.07-1.48). Conclusions: Our study observed an increased risk of early mortality among children living in persistent poverty census tracts and among racial/ethnic minorities. Future studies should explore potential mediators of the association between persistent poverty and early mortality, including health insurance, treatment access, and individual-level socioeconomic status.

Citation Format: Emma Hymel, Josiane Kabayundo, Krishtee Napit, Shinobu Watanabe-Galloway. Persistent poverty is associated with risk of early mortality among children with cancer: An analysis of SEER data [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr PR007.
Circulating miRNAs as Biomarkers of Subclinical Atherosclerosis Associated with Severe Obesity before and after Bariatric Surgery
Authors: Carmona-Maurici Júlia , Ricart-Jané David , Viñas Anna , López-Tejero Maria Dolores , Eskubi-Turró Iratxe , Miñarro Antonio , Baena-Fustegueras Juan Antonio , Peinado-Onsurbe Julia , Pardina Eva
Published: September 2024

Introduction: Severe obesity results in high cardiovascular risk (CVR), increasing morbidity, and mortality. New and improved methods are needed to detect cardiovascular diseases rapidly in severe obesity. microRNAs (miRNAs) has shown promise as diagnostic tools. This study aimed to identify plasma miRNAs useful as biomarkers of CVR in people with severe obesity. Methods: The study included 66 people with severe obesity classified in groups with atheroma (n = 32) and free of plaques (n = 34). Plasma samples were collected 1 month before bariatric surgery and at 6 and 12 months of follow-up. Participants were screened for the levels of 188 miRNAs, and 24 promising candidates were individually validated by quantitative polymerase chain reaction. Results: After validation, 5 of the 24 miRNAs showed significant differences over time in both groups: miR-375 increased after bariatric surgery, whereas miR-144-5p, miR-20a-3p, miR-145-5p, and miR-21-3p exhibited decreased expression after bariatric surgery. The expression of 3 of the 24 miRNAs also differed between patients with and without atheroma: subjects with plaque had lower miR-126 but higher miR-21-3p and miR-133a-3p. Only miR-133a-3p exhibited exceptional discriminatory ability between subjects with and without plaque (area under the curve, 0.90; 95% confidence interval, 0.81–0.99). Conclusion: A specific signature of c-miRNA comprising miR-375, miR-144-5p, miR-20a-3p, miR-145-5p, and miR-21-3p may facilitate CVR monitoring after bariatric surgery. Furthermore, miR-21-3p, miR-126-3p, and miR-133a-3p show potential as specific biomarkers for subclinical atherosclerosis, with miR-133a-3p potentially able to diagnose subclinical atherosclerosis early in severe obesity.
Lower Pole Stones Are Associated with Low Stone-Free Rates in Retrograde Intrarenal Surgery: A Myth or Fact? – A Matched Case-Control Study from the RIRSearch Group
Authors: Simsekoglu Muhammed Fatih , Özman Oktay , Cakir Hakan , Teke Kerem , Çınar Önder , Akgül Murat , Tuna Mustafa Bilal , Başataç Cem , Sancak Eyüp Burak , Sıddıkoğlu Duygu , Yazici Cenk , Başeskioğlu Barbaros , Akpinar Haluk , Onal Bulent
Published: September 2024

Introduction: There are conflicting results in the literature regarding the efficacy of retrograde intrarenal surgery (RIRS) in lower pole stones. This study aimed to evaluate RIRS outcomes in lower pole stones by forming matched case-control groups. Methods: The data of 491 patients who were diagnosed with kidney stones and underwent RIRS were retrospectively included in the study. A total of 209 patients with lower pole stones (Group 1) and 282 patients with pelvic stones (Group 2) were matched at a 1:1 ratio in terms of stone burden, stone density, preoperative double-J stenting status, and a previous history of shock wave lithotripsy, yielding 159 patients in each group. A computed tomography scan was performed to evaluate the stone-free status. The primary outcome was stone-free status 1 month after RIRS. Results: After case-control matching, the median age was 49 years (interquartile range [IQR]: 40–58) in Group 1 and 50 years (IQR: 35–60) in Group 2 (p = 0.388). The median stone burden values of Group 1 and Group 2 were 415.3 mm3 (IQR: 176.1–858.2) and 503.3 mm3 (IQR: 282.5–864), respectively (p = 0.100). After RIRS, stone-free status was achieved by 126 of the 159 (79.2%) in Group 1 and 133 of the 159 (83.6%) patients in Group 2 (p = 0.387). The groups were similar in terms of perioperative complications (4.4% in Group 1 and 3.8% in Group 2, p = 0.777), postoperative complications (13.8% in Group 1 and 10.3% in Group 2, p = 0.393), and median operation time (60 min in both, p = 0.230). A longer median fluoroscopy time was noted in Group 1 compared to Group 2 (26 s and 3 s, respectively, p = 0.013). Conclusions: Stone-free rates and complications were comparable between the patients with lower pole and pelvic stones after RIRS. However, lower pole stones are associated with longer fluoroscopy time. RIRS can be performed effectively for the treatment of lower pole stones.
Focal Pulsed Field Ablation for Premature Ventricular Contractions: A Multicenter Experience
Authors: Della Rocca Domenico Giovanni , Cespón-Fernández María , Keelani Ahmad , Raffa Santi , Pannone Luigi , Almorad Alexandre , Ströker Erwin , Borisov Georgi , Bala Gezim , Sieira Juan , Vetta Giampaolo , Alothman Obaida , Sorgente Antonio , Audiat Charles , Overeinder Ingrid , Frommhold Markus , Del Monte Alvise , La Meir Mark , Natale Andrea , Chierchia Gian-Battista , Geller J. Christoph , de Asmundis Carlo , Sarkozy Andrea , Doundoulakis Ioannis , Marcon Lorenzo , Monaco Cinzia , Lombardo Ilenia , Nakasone Kazutaka , Scacciavillani Roberto , Eltzov Ivan
Published: September 2024

BACKGROUND:

Pulsed field ablation (PFA) is a novel technology for catheter-based atrial arrhythmia treatment. Evidence of its application for ventricular arrhythmia ablation is still limited. In this study, we describe the feasibility and efficacy of focal PFA for premature ventricular contraction (PVC) ablation.

METHODS:

A prospective cohort of 20 patients referred for PVC ablation at 2 centers was enrolled, regardless of the presence of structural heart disease, PVC morphology, or previous ablation attempts. All procedures were performed using the CENTAURI System in combination with contact force sensing catheters and 3-dimensional electroanatomical mapping systems. Energy output and the number of applications were left to the operator’s discretion.

RESULTS:

Eleven (55%) procedures were conducted under general anesthesia, 6 (30%) under deep sedation, and 3 (15%) under light sedation. Muscular contraction was observed in one case (5%). Median procedural and fluoroscopy times were 95.5 and 6.55 minutes, respectively. The median number of PFA applications was 8 with a median contact force of 10
g
. A statistically significant (76%) reduction was observed in mean peak-to-peak bipolar electrogram voltage before and after ablation (0.707 versus 0.098 mV;
P
=0.008). Ventricular irritative firing was observed in 11 (55%) patients after PFA. The median follow-up was 120 days. Acute procedural success was achieved in 17 of 20 (85% [95% CI, 0.70–1]) patients. Two of the patients with procedural failure had late success with >80% clinical PVC burden suppression during follow-up, and 2 of 17 patients with acute success had late PVC recurrence, which accounts for a total of 17 of 20 (85% [95% CI, 0.70–1]) patients with chronic success. Transient ST-segment depression occurred in 1 patient, and the right bundle branch block was induced in 2 others (permanently only in one case).

CONCLUSIONS:

PVC ablation using a focal PFA is feasible, effective, and safe, with promising acute and long-term results in several ventricular locations. Irritative firing is frequently observed. Coronary evaluation should be considered when targeting the outflow tract.
Optogenetic Functional Activation Is Detrimental During Acute Ischemic Stroke in Mice
Authors: Sugimoto Kazutaka , Chung David Y. , Fischer Paul , Takizawa Tsubasa , Qin Tao , Yaseen Mohammad A. , Sakadžić Sava , Ayata Cenk
Published: September 2024

BACKGROUND:

Functional activation of the focal ischemic brain has been reported to improve outcomes by augmenting collateral blood flow. However, functional activation also increases metabolic demand and might thereby worsen outcomes. Indeed, preclinical and clinical reports have been conflicting. Here, we tested the effect of functional activation during acute ischemic stroke using distal middle cerebral artery occlusion in anesthetized mice.

METHODS:

Using transgenic mice expressing channelrhodopsin-2 in neurons, we delivered functional activation using physiological levels of transcranial optogenetic stimulation of the moderately ischemic cortex (ie, penumbra), identified using real-time full-field laser speckle perfusion imaging during a 1-hour distal microvascular clip of the middle cerebral artery. Neuronal activation was confirmed using evoked field potentials, and infarct volumes were measured in tissue slices 48 hours later.

RESULTS:

Optogenetic stimulation of the penumbra was associated with more than 2-fold larger infarcts than stimulation of the contralateral homotopic region and the sham stimulation group (n=10, 7, and 9; 11.0±5.6 versus 5.1±4.3 versus 4.1±3.7 mm
3
;
P
=0.008, 1-way ANOVA). Identical stimulation in wild-type mice that do not express channelrhodopsin-2 did not have an effect. Optogenetic stimulation was associated with a small increase in penumbral perfusion that did not explain enlarged infarcts.

CONCLUSIONS:

Our data suggest that increased neuronal activity during acute focal arterial occlusions can be detrimental, presumably due to increased metabolic demand, and may have implications for the clinical management of hyperacute stroke patients.
The Rabbinical Coalition of Libyan Jewry under the Leadership of Rabbi Eliyahu Bekhor Ḥazzan
Authors: Atia Ronel
Published: September 2024

The extent of a community rabbi’s ability to change the practices of his flock may be a reflection of his status. The stronger his status, the better he can effect change, even if his reform will replace prior practice. In this article, I present two examples in which the dayyanim (rabbinical judges) of the Jewish community in the late nineteenth century acted against Rabbi Ḥazzan during the latter’s term as the Ḥakham Bashi of the Jewish community in Libya. The examples, both dealing with Torah affairs, occurred in close temporal proximity and may be instructive of the atmosphere between Ḥazzan and part of the Jewish community at that time. Notably, shortly after these events, Rabbi Ḥazzan decided to resign his post and move on to a rabbinical position in the Alexandria community.
Why Prophesying Deliverance Still Matters
Authors: Sanders Cheryl J.
Published: September 2024

This paper recognizes the 40th anniversary of the publication of Prophesy Deliverance! by Cornel West, and acknowledges the broad impact of his intellectual leadership. It begins with the important question of whether West has centered or marginalized Pentecostal thought and culture in the presentation of his basic argument regarding the evolution of Black critical thought and prophetic Christianity. Next is an exploration of how West’s ideas about Black revolutionary Christianity find expression in recent studies of Black Pentecostalism, with particular attention to the Pentecostal social imaginary framed by Dale Coulter and by Keri Day.
When Marx Caught the Holy Ghost
Authors: Sekou Osagyefo Uhuru
Published: September 2024

In Prophesy Deliverance, Cornel West calls on Black liberation theologians to critical engage with Marxist thought. Instigated by Black Lives Matter movement, this article explores the convergence of Black Pentecostalism, Marxism, and liberation theology, highlighting their collective potential to address racial capitalism and systemic injustice. Drawing on Black existential thought, insurgent theologies, and Pentecostal praxis, it proposes a theology that is anti-capitalist, anti-imperialist, antiracist, and antisexist, emphasizing the lived experiences of the Black poor. It argues for a Black Pentecostal Liberation Theology that critiques racial, economic, and gender oppressions through a revolutionary Christian lens. This framework seeks to transcend the historical legacies of slavery and racial discrimination, advocating for a transformative praxis rooted in Black struggle and resistance.
Description of the larvae of Epigomphus rufus Bota-Sierra & Novelo-Gutiérrez, 2020, and E. brillantina Bota-Sierra & Novelo-Gutiérrez, 2020 (Odonata: Gomphidae)
Authors: NOVELO-GUTIÉRREZ RODOLFO , BOTA-SIERRA CORNELIO ANDRÉS
Published: September 2024

The larvae of Epigomphus rufus Bota-Sierra & Novelo-Gutiérrez, 2020, and E. brillantina Bota-Sierra & Novelo-Gutiérrez, 2020 (by supposition) are described, figured and compared with other described larvae of the genus. The larva of E. rufus is characterized by 3rd antennomere spindle-shaped, 2.12x as long as widest part; ligula with a ventral row of 8–10 short, truncate teeth on middle; abdomen lateral spines on S7–9 divergent and upturned; middorsal third of abdomen reddish-brown. The larva of E. brillantina is characterized by 3rd antennomere 2x as long as widest part, 4th antennomere more or less subspherical; ligula with 9–10 teeth, and lateral margins of S7–9 serrate.
A new species of the genus Ceraphron Jurine (Hymenoptera: Ceraphronidae) from India
Authors: GHOSH AMIT KUMAR , KUMAR VIKAS , RAMESHKUMAR ANANDHAN , TYAGI KAOMUD
Published: September 2024

Ceraphron initium sp. nov. is described and illustrated from Nagaland state of India based on male specimens. The genitalia of this new species is studied and compared with the closely related species C. semira Salden & Peters and C. thompsoni (Dalla Torre).