bluuebunny/crossref_metadata_2025_split huggingface dataset:
Morality Appraisals in Consumer Responsibilization
Authors: Barnhart Michelle , Huff Aimee Dinnín , Scott Inara 
Published: June 2023

Abstract
In recent decades, U.S. gun rights lobbying groups, politicians, courts, and market actors have sought to responsibilize U.S. consumers to use firearms to address the societal problem of crime. These efforts center an interpretation of the constitutional right to keep and bear arms guaranteed by the Second Amendment as an entitlement for individuals to practice armed self-defense. Using interview and online discussion data, this research investigates consumers’ responses to responsibilization for this morally fraught set of behaviors, and the role of consumers’ various understandings of the right to bear arms in these responses. Findings show that consumers consider multiple, specific armed protection scenarios and accept responsibilization in only a portion of these scenarios while rejecting it for the remainder. Acceptance is determined by their appraisals of the morality of consumer responsibilization subprocesses. Consumers’ understanding of the constitutional right serves as a heuristic in these appraisals, with some understandings leading consumers to accept responsibilization across a much larger proportion of scenarios than others. Contributions include illustrating response to consumer responsibilization as a proportionality; illuminating consumers’ active role in appraising responsibilizing efforts; and demonstrating how some consumers come to understand a responsibilized behavior as a moral entitlement.
The interplay of solvent–drug–protein interactions during albumin nanoparticles formulations for temozolomide delivery to brain cancer cells
Authors: Helal Dina O , Abdel-Mottaleb Mona M A , Kamel Amany O , Rouatbi Nadia , Han Shunping , Geneidi Ahmed-Shawky , Al-Jamal Khuloud T , Awad Gehanne A S 
Published: June 2023

Abstract

Objectives
Temozolomide (TMZ), the first line for glioma therapy, suffers from stability at physiological pH. TMZ was selected as a challenging model drug for loading into human serum albumin nanoparticles (HSA NPs). Our aim is to optimise the conditions for TMZ loading into HSA NPs while ensuring TMZ stability.

Methods
Blank and TMZ–HSA NPs were fabricated using the de-solvation technique and the effect of different formulation parameters was evaluated.

Key findings
For blank NPs, crosslinking time had no significant effect on NPs’ size while acetone produced significantly smaller particles than ethanol. Upon drug loading, though TMZ was stable in acetone and ethanol as single agents yet, ethanol-based NPs showed misleadingly high EE% due to drug instability in ethanol formulations as evident by the UV spectrum.
The optimum conditions for drug-loaded particles were: 10 mg/ml HSA, 4 mg TMZ using acetone, yielded NPs with 145 nm in diameter, ξ of −16.98 mV and 0.16% DL. The selected formula reduced the cell viabilities of GL261 glioblastoma cells and BL6 glioblastoma stem cells to 61.9% and 38.3%, respectively.

Conclusions
Our results corroborated that careful manipulation of TMZ formulation processing parameters is crucial for encapsulating such chemically unstable dug while simultaneously ensuring its chemical stability.
Successful surgical removal of a cutaneous lesion compatible with gigantic vascular eccrine spiradenoma: a rare case report
Authors: Alnafee Reem A , Almasaud Aram K , Alshamrani Abdullah M , Alrasheedi Saud D , Alzahrani Abdulrahman J , Alqahtani Adel S 
Published: June 2023

AbstractGiant vascular eccrine spiradenoma (GVES) is an uncommon type of eccrine spiradenoma (ES). Compared to an ES, this is characterized by a greater degree of vascularity and a bigger size overall. In clinical practice, it is frequently mistaken for a vascular or malignant tumor. To achieve an accurate diagnosis of GVES via biopsy and successfully perform the surgical removal of a cutaneous lesion in the left upper abdomen compatible with GVES. We present a 61-year-old female with the lesion accompanied by on-and-off pain, bloody discharge and skin changes surrounding the mass treated surgically. However, there was no fever, weight loss, trauma or family history of malignancy or cancer managed by surgical excision. The patient recovered well postoperatively and was discharged on the same day with a 2-week follow-up. The wound got healed, the clips were removed on Day 7 postoperatively, and there was no requirement for further follow-up.
Distal colonic atresia: a case report
Authors: Allert Tom , Schellerer Vera 
Published: June 2023

Abstract
Colonic atresia (CA) is a rare disease with an incidence range between one of 20 000 and one of 66 000 live births. Most CA are located within the proximal colon; distal CA are even rarer. Because of its rarity, another case shall be described herewith. A 37th week of pregnancy born child was noticed occurring multiple vomiting, a distended abdomen and additional whitish-bloody stool shortly thereafter. In the first operation, a double-barrel stoma was created. After sufficient weight gain and alignment of the stoma ends, a secondary anastomosis was created in the child after 2 months. The diagnosis can be made reliably on the basis of an X-ray and leads to a good outcome with prompt surgical intervention. However, accompanying malformations should always be considered.
The nuclear-localized RNA helicase 13 is essential for chloroplast development in Arabidopsis thaliana
Authors: Luo Pan , Shi Ce , Zhou Yi , Zhou Jiao , Zhang Xuecheng , Wang Yukun , Yang Yong , Peng Xiongbo , Xie Tingting , Tang Xingchun 
Published: June 2023

Abstract
The chloroplast is a semi-autonomous organelle with a double membrane structure, and its structural stability is a prerequisite for its correct function. Chloroplast development is regulated by known nuclear-encoded chloroplast proteins or proteins encoded within the chloroplast itself. However, the mechanism of chloroplast development regulated by other organelles remains largely unknown. Here, we report that the nuclear-localized DEAD-box RNA helicase 13 (RH13) is essential for chloroplast development in Arabidopsis thaliana. RH13 is widely expressed in tissues and localized to the nucleolus. A homozygous rh13 mutant shows abnormal chloroplast structure and leaf morphogenesis. Proteomic analysis showed that the expression levels of photosynthesis-related proteins in chloroplasts were reduced due to loss of RH13. Furthermore, RNA-sequencing and proteomics data revealed decreases in the expression levels of these chloroplast-related genes, which undergo alternative splicing events in the rh13 mutant. Taken together, we propose that nucleolus-localized RH13 is critical for chloroplast development in Arabidopsis.
GRB 221009A afterglow from a shallow angular structured jet
Authors: Gill Ramandeep , Granot Jonathan 
Published: June 2023

ABSTRACT
Exceptionally bright gamma-ray burst (GRB) afterglows can reveal the angular structure of their jets. GRB jets appear to have a narrow core (of half-opening angle θc), beyond which their kinetic energy drops as a power-law with angle θ from the jet’s symmetry axis, $E_{\mathrm{ k},\rm iso}(\theta)\propto [1+(\theta /\theta _\mathrm{ c})^2]^{-a/2}$. The power-law index a reflects the amount of mixing between the shocked jet and confining medium, which depends on the jet’s initial magnetization. Weakly magnetized jets undergo significant mixing, leading to shallow (a ≲ 2) angular profiles. We use the exquisite multiwaveband afterglow observations of GRB 221009A to constrain the jet angular structure using a dynamical model that accounts for both the forward and reverse shocks, for a power-law external density profile, next ∝ R−k. Both the forward shock emission, that dominates the optical and X-ray flux, and the reverse shock emission, that produces the radio afterglow, require a jet with a narrow core (θc ≈ 0.021) and a shallow angular structure (a ≈ 0.8) expanding into a stellar wind (k ≈ 2). Moreover, these data appear to favour a small fraction (ξe ≈ 10−2) of shock heated electrons forming a power-law energy distribution in both shocks.
ATRT-03. THE ORAL IRON-MIMETIC GALLIUM MALTOLATE INHIBITS ATRT IN VIVO – IMAGING AND HISTOLOGICAL CHARACTERIZATION
Authors: Al-Gizawiy Mona , Wujek Robert T , Zoss Casey J , Tanaka Ryuma , Mirza Shama P , Chitambar Christopher R , Schmainda Kathleen M 
Published: June 2023

Abstract

BACKGROUND
Atypical teratoid rhabdoid tumor (ATRT) is a highly aggressive CNS tumor that is associated with poor outcome. This dire prognosis is due in part to its poor response to the limited treatment options available. Iron and iron proteins play a key role in the growth of many solid cancers, including brain tumors. Our published studies show that the ferrobiology of brain tumors can be exploited for therapeutic purposes. Here, we further demonstrate the inhibitory effects of oral gallium maltolate (GaM) in pediatric ATRT in vivo.

METHODS
Pediatric CHLA-266 ATRT cells were stereotactically implanted into the right striatum of male athymic rats. Advanced MR imaging at 9.4T was carried out weekly starting two weeks after implantation. Daily oral GaM (50mg/kg) or vehicle were provided on tumor confirmation. Longitudinal advanced MRI parameters were processed for enhancing tumor ROIs in OsiriX 8.5.1 (lite) with Imaging Biometrics Software (Imaging Biometrics LLC). Statistical analyses included Kaplan-Meier survival plots, linear mixed model comparisons, and t-statistic for slopes comparison (as indicator of tumor growth rate).

RESULTS
In concordance with our previous in vitro work, in vivo ATRT xenografts were found to be highly sensitive to oral GaM. Median overall survival was 89 days in the control group and 170 days in the treatment group (p=0.011). GaM-treated xenograft tumors grew at a significantly slower rate than control tumors (p&lt;0.0001). On MRI, untreated ATRT xenograft tumors, as their clinical counterparts, tended to localize near the ventricle and occasionally invade it. Histologically, xenograft tumors in our rat model recapitulated the histological features of human ATRT. A significant reduction in MIB-1% and mitotic index (p&lt;0.001 and p&lt;0.05, respectively) was seen in the treatment group. Transferrin receptor and H-ferritin expression in GaM-treated tumors illustrated cellular iron deprivation.

CONCLUSION
Monotherapy with GaM profoundly inhibited ATRT growth and prolonged survival in vivo.
ATRT-06. ETMR TUMORIGENESIS MIRRORS RADIAL GLIAL DEVELOPMENT
Authors: Yao Fupan , Mumal Iqra , Raghuram Nikhil , Xu Liming , Liu Laurie , Ho Ben , Huang Annie 
Published: June 2023

Abstract
Embryonal tumors with multilayered rosettes (ETMRs) are rare pediatric brain tumors defined primarily by overexpression of the C19MC microRNA cluster. These tumors affect mostly children under the age of 3. However, little is known about the origin and developmental contexts of ETMRs. We hypothesized that the early onset of these tumors suggests an embryonic tumorigenic event. To elucidate the embryonic contexts of which ETMRs arise, we curated three mouse embryogenesis datasets representing the full spectrum of murine embryonic development. We generated timepoint structure signatures of this atlas and projected them onto a single nuclei RNA sequencing dataset of 8 primary ETMRs. Consistent with existing literature, we discovered that ETMRs resemble a spectrum of radial glial, neuronal, and oligodendrocytic cell types. We also recapitulated potential ETMR driver mechanisms such as overexpression of WNT and SHH signaling by gene set enrichment analysis. We validated the enrichment of lineage and driver markers through GSEA and marker gene enrichment in a separate cohort of ETMRs characterized by bulk RNA sequencing. Taken together, the embryonic context of ETMR development may play crucial roles in the early identification and treatments of this lethal disease.
ATRT-10. SINGLE-CELL TRANSCRIPTOME ANALYSIS REVEALS CELLULAR HIERARCHIES AND THERAPEUTIC VULNERABILITIES OF ETMR
Authors: Beck Alexander , Gabler Lisa , Cruzeiro Gustavo A V , Lambo Sander , Englinger Bernhard , Shaw McKenzie L , Hack Olivia A , Liu Ilon , Junior Carlos A O de Biagi , Haase Rebecca D , Klenner Marbod , Freidel Pia , Madlener Sibylle , Mayr Lisa , Senfter Daniel , Peyrl Andreas , Slavc Irene , Lötsch Daniela , Dorfer Christian , Haberler Christine , Pfister Stefan M , Baird Lissa , Chi Susan N , Alexandrescu Sanda , Gojo Johannes , Kool Marcel , Hovestadt Volker , Filbin Mariella G 
Published: June 2023

Abstract
Embryonal tumors with multilayered rosettes (ETMR) are malignant brain tumors that occur predominantly in infants and young children. Most patients die within two years of diagnosis, and more effective, targeted therapies are urgently needed. To better characterize the oncogenic mechanisms of key driver alterations and to identify novel therapeutic targets, we set out to study the cellular heterogeneity of ETMR using single-cell RNA sequencing.
Analyses conducted on &gt;4,000 high-quality cells collected from eleven primary and relapse specimens revealed a common cellular hierarchy across all tumors: A highly proliferative neural stem cell-like population (SOX2+) that gives rise to intermediate progenitors (NEUROD1/NEUROG1+) and more differentiated neuron-like cells (STMN2/4+). These malignant cell populations closely overlap with histological patterns of ETMRs, as confirmed by multiplexed immunofluorescence microscopy on patients’ tumors.
Comparison to single-cell datasets from human fetuses indicated high resemblance to normal cortical neurogenesis but also revealed key tumor-specific differences. These include expression of the chromosome 19 miRNA cluster (C19MC, the presumed driver in ~90% of ETMRs), which was restricted to the malignant stem cell-like population. Investigating oncogenic mechanisms of C19MC (comprising 46 miRNA genes) through transcriptome-wide RNA immunoprecipitation analysis, we identified extensive target gene regulation for most C19MC members, including distinct regulators of cell cycle, pluripotency, and neuronal differentiation. Silencing of C19MC families with antisense oligonucleotides resulted in pronounced reduction of ETMR cell line growth, indicating potential avenues for therapeutic targeting in the future.
To identify more immediately actionable targets, we investigated inter-cellular signaling between malignant cell populations of ETMRs. Interestingly, we identified marked FGFR and NOTCH receptor-ligand interactions common to all tumors. An in vitro screen of experimental and approved small molecule inhibitors designed to target these interactions nominated several promising candidates for clinical evaluation. Our unpublished results provide much needed insight into targeting ETMR cellular states using multiple modes of action.
ATRT-11. DEVELOPMENT OF NOVEL PRECLINICAL MODELS AND THERAPEUTIC STRATEGIES FOR ETMR
Authors: Cocito Carolina , Arias-Stella Esteban Uceda , Zhang Xiaohu , McKnight Crystal , Itkin Zina , Klumpp-Thomas Carleen , Cruzeiro Gustavo Alencastro Veiga , Chi Susan N , Pisapia David J , Filbin Mariella G , Dahmane Nadia , Thomas Craig J , Greenfield Jeffrey P 
Published: June 2023

Abstract
Embryonal Tumor with Multilayered Rosettes (ETMR) is a very rare, aggressive pediatric brain tumor with a dismal 5-year overall survival rate. Few genetic aberrations in miRNA clusters and processing machinery have been detected in ETMRs with 90% of ETMR patients having the C19MC amplification. ETMRs show heterogenous histopathological features, including regions of abundant neuropil, hypercellular regions with multilayered rosettes, and papillary structures resembling primitive neuroectoderm. This unique histology, together with the detection of C19MC or DICER alterations, are necessary for diagnosis. The cellular and molecular mechanisms underlying ETMR development is poorly understood, and targeted therapeutics have not been developed due to scarcity of preclinical models.
To expand knowledge of ETMR biology and accelerate the design of novel, it is thus essential to develop preclinical models. We have generated a novel patient-derived ETMR cell line from a resected patient tumor sample (CTBP-03A) and created two patient-derived xenograft (PDX) models (CTBP-03A and CBTP-38). We have used these unique patient-derived cell lines to identify mechanisms driving ETMR development and progression. To identify novel therapeutic targets, we conducted high-throughput drug screening (HTDS) utilizing 2480 approved and investigational drugs, against the CBTP-03A cell line. Among the candidate drugs showing an inhibitory effect on CBTP-03, 63 compounds were selected based on their activity, CNS penetration ability, mechanism of action, and bioavailability, if known. The 63 potency-selected hits were screened in an all-versus-all format, totaling 1953 combinations. The rapidity of action of the top choice compounds used as single agent or in double and triple combination was assessed by caspase glow assay. This initial combination screen identified DNA replication stress and FGF signaling as potential new drug combinations for ETMR.
We will thus describe the first combinatorial HTDS on two novel ETMR patient-derived cell lines and potential drug combination strategies for the treatment of ETMR.
ATRT-13. ASSESSMENT OF MITOCHONDRIAL BIOENERGETICS AND FISSION-FUSION DYNAMICS IN ETMR
Authors: Liapis Evangelos , Pamreddy Annapurna , Maas Allison , Hanson Derek , Carter Claire 
Published: June 2023

Abstract

BACKGROUND
Embryonal tumor with multilayered rosettes (ETMR) is a deadly pediatric brain tumor with limited available therapeutic options. Dysregulated mitochondrial bioenergetics and dynamics have been linked to the initiation and progression of diverse human cancers, however, their role in ETMR pathobiology remains unknown. We used the primary ETMR cell line, BT183, and an in-house developed human neural stem cell (NSC) line to evaluate mitochondrial morphology, bioenergetics and fission-fusion dynamics involved in ETMR growth and aggression.

METHODS
Mitochondrial morphology was determined by widefield immunofluorescence and dSTORM super-resolution microscopy in BT183 and NSC monolayers and by TEM in BT183 and NSCs grown as neurospheres. Relative expression of mitochondrial proteins were quantified in BT183 and NSC lysates by western blotting.

RESULTS
Widefield immunofluorescence and super-resolution imaging revealed profound differences in mitochondrial morphology in BT183 compared to NSCs. BT183 mitochondria appear as fragmented, rounded structures, with little interconnectivity, while NSC mitochondria present a typical elongated, filamentous morphology. These findings were corroborated by TEM image analysis of BT183 and NSC neurospheres, which revealed additional morphological alterations in BT183 mitochondria at the ultrastructural level, including aberrant cristae structure. Western blot analysis of BT183 and NSC lysates showed up to 5-fold differential expression of mitochondrial OXPHOS, glycolytic and fission-fusion proteins in the two cell types. Fission promoters phospho-Drp1 and MFF displayed significantly higher expression in BT183 relative to NSCs, whereas fusion-inducing proteins Opa1 and Miro2 showed significantly lower differential expression in BT183.

CONCLUSIONS
BT183 cells exhibited striking mitochondrial fragmentation and differential expression of proteins involved in fission-fusion, OXPHOS and glycolysis when compared to normal human NSCs. Ongoing studies include the analysis of mitochondrial structure and morphology in patient samples to validate our in-vitro findings, in addition to in-vitro metabolic flux analysis and targeted protein depletion studies to identify druggable pathways based on mitochondrial function and dynamics.
ATRT-14. ASSESSMENT OF MITOCHONDRIAL BIOENERGETICS AND FISSION-FUSION DYNAMICS IN ETMR
Authors: Liapis Evangelos , Pamreddy Annapurna , Maas Allison , Hanson Derek , Carter Claire 
Published: June 2023

Abstract

BACKGROUND
Embryonal tumor with multilayered rosettes (ETMR) is a deadly pediatric brain tumor with limited available therapeutic options. Dysregulated mitochondrial bioenergetics and dynamics have been linked to the initiation and progression of diverse human cancers, however, their role in ETMR pathobiology remains unknown. We used the primary ETMR cell line, BT183, and an in-house developed human neural stem cell (NSC) line to evaluate mitochondrial morphology, bioenergetics and fission-fusion dynamics involved in ETMR growth and aggression.

METHODS
Mitochondrial morphology was determined by widefield immunofluorescence and dSTORM super-resolution microscopy in BT183 and NSC monolayers and by TEM in BT183 and NSCs grown as neurospheres. Relative expression of mitochondrial proteins were quantified in BT183 and NSC lysates by western blotting.

RESULTS
Widefield immunofluorescence and super-resolution imaging revealed profound differences in mitochondrial morphology in BT183 compared to NSCs. BT183 mitochondria appear as fragmented, rounded structures, with little interconnectivity, while NSC mitochondria present a typical elongated, filamentous morphology. These findings were corroborated by TEM image analysis of BT183 and NSC neurospheres, which revealed additional morphological alterations in BT183 mitochondria at the ultrastructural level, including aberrant cristae structure. Western blot analysis of BT183 and NSC lysates showed up to 5-fold differential expression of mitochondrial OXPHOS, glycolytic and fission-fusion proteins in the two cell types. Fission promoters phospho-Drp1 and MFF displayed significantly higher expression in BT183 relative to NSCs, whereas fusion-inducing proteins Opa1 and Miro2 showed significantly lower differential expression in BT183.

CONCLUSIONS
BT183 cells exhibited striking mitochondrial fragmentation and differential expression of proteins involved in fission-fusion, OXPHOS and glycolysis when compared to normal human NSCs. Ongoing studies include the analysis of mitochondrial structure and morphology in patient samples to validate our in-vitro findings, in addition to in-vitro metabolic flux analysis and targeted protein depletion studies to identify druggable pathways based on mitochondrial function and dynamics.