bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nicotinamide-N-methyltransferase regulates lipid metabolism via SAM and 1-methylnicotinamide in the AML12 hepatocyte cell line
Authors: Yoda Mayuko , Mizuno Rin , Izumi Yoshihiro , Takahashi Masatomo , Bamba Takeshi , Kawaoka Shinpei 
Published: April 2023

Abstract
Nicotinamide-N-methyltransferase (NNMT) is an enzyme that consumes S-adenosyl-methionine (SAM) and nicotinamide (NAM) to produce S-adenosyl-homocysteine (SAH) and 1-methylnicotinamide (MNAM). How much NNMT contributes to the quantity regulation of these four metabolites depends on whether NNMT is a major consumer or producer of these metabolites, which varies among various cellular contexts. Yet, whether NNMT critically regulates these metabolites in the AML12 hepatocyte cell line has been unexplored. To address this, we knockdown Nnmt in AML12 cells and investigate the effects of Nnmt RNAi on metabolism and gene expression. We find that Nnmt RNAi accumulates SAM and SAH, whereas it reduces MNAM with NAM being unaltered. These results indicate that NNMT is a significant consumer of SAM and critical for MNAM production in this cell line. Moreover, transcriptome analyses reveal that altered SAM and MNAM homeostasis is accompanied by various detrimental molecular phenotypes, as exemplified by the down-regulations of lipogenic genes, such as Srebf1. Consistent with this, oil-red O-staining experiments demonstrate the decrease of total neutral lipids upon Nnmt RNAi. Treating Nnmt RNAi AML12 cells with cycloleucine, an inhibitor of SAM biogenesis suppresses SAM accumulation and rescues the decrease of neutral lipids. MNAM also shows activity to elevate neutral lipids. These results suggest that NNMT contributes to lipid metabolism by maintaining proper SAM and MNAM homeostasis. This study provides an additional example where NNMT plays a critical role in regulating SAM and MNAM metabolism.
Ambivalent role of FasL in murine acute graft-versus-host-disease
Authors: Bernard-Bloch Robin , Lebrault Eden , Li Xiaofan , Sutra Del Galy Aurélien , Garcia Arlette , Doliger Christelle , Parietti Véronique , Legembre Patrick , Socié Gérard , Karray Saoussen 
Published: April 2023

Abstract
Fas ligand is increased in several immune-mediated diseases, including acute graft-versus-host disease, a donor cell–mediated disorder post–hematopoietic stem cell transplantation. In this disease, Fas ligand is involved in T-cell–mediated damage to host tissues. However, the role of its expression on donor non–T cells has, so far, never been addressed. Using a well-established CD4- and CD8-mediated graft-versus-host disease murine model, we found that precocious gut damage and mice mortality are increased with a graft of donor T- and B-depleted bone marrow cells devoid of Fas ligand as compared with their wild-type counterparts. Interestingly, serum levels of both soluble Fas ligand and IL-18 are drastically reduced in the recipients of Fas ligand–deficient grafts, indicating that soluble Fas ligand stems from donor bone marrow–derived cells. In addition, the correlation between the concentrations of these 2 cytokines suggests that IL-18 production arises through a soluble Fas ligand–driven mechanism. These data highlight the importance of Fas ligand–dependent production in IL-18 production and in mitigating acute graft-versus-host disease. Overall, our data reveal the functional duality of Fas ligand according to its source.
Real-World Effectiveness of Gelatin-Thrombin Matrix Sealant on Blood Loss in Adolescent Idiopathic Scoliosis Patients Undergoing Posterior Spinal Fusion
Authors: Mimura Tetsuhiko , Ikegami Shota , Uehara Masashi , Oba Hiroki , Hatakenaka Terue , Kamanaka Takayuki , Miyaoka Yoshinari , Kurogochi Daisuke , Fukuzawa Takuma , Koseki Michihiko , Takahashi Jun 
Published: April 2023

Study Design.
Retrospective cohort study with interrupted time series analysis.

Objective.
To examine the clinical effectiveness of gelatin-thrombin matrix sealant (GTMS) on blood loss reduction after adolescent idiopathic scoliosis (AIS) surgery.

Summary of Background Data.
The real-world effectiveness of GTMS on blood loss reduction in AIS surgery has not been determined.

Patients and Methods.
The medical records of patients receiving AIS surgery were retrospectively collected during a period before GTMS approval at our institution (January 22, 2010–January 21, 2015) as well as during a postintroduction period (January 22, 2015–January 22, 2020). The primary outcomes were intraoperative blood loss, drain output over 24 hours, and total blood loss (intraoperative blood loss + drain output over 24 h). Interrupted time series analysis using a segmented linear regression model was used to estimate the effect of GTMS on blood loss reduction.

Results.
A total of 179 AIS patients [mean age (range): 15.4 (11–30) yr; 159 females and 20 males; 63 preintroduction patients and 116 postintroduction patients] were included. After its introduction, GTMS was used in 40% of cases. Interrupted time series analysis revealed changes of −340 mL (95% CI: −649 to −31, P = 0.03) for intraoperative blood loss, −35 mL (95% CI: −124 to 55, P = 0.44) for drain output over 24 hours, and −375 mL (95% CI: −698 to −51, P = 0.02) for total blood loss.

Conclusions.
The availability of GTMS was significantly associated with reduced intraoperative and total blood loss in AIS surgery. GTMS use as needed is recommended to control intraoperative bleeding in the setting of AIS surgery.

Level of Evidence.
3.
DENV-specific IgA contributes protective and non-pathologic function during antibody-dependent enhancement of DENV infection
Authors: Wegman Adam D. , Waldran Mitchell J. , Bahr Lauren E. , Lu Joseph Q. , Baxter Kristen E. , Thomas Stephen J , Waickman Adam T. 
Published: April 2023

ABSTRACTDengue represents a growing public health burden worldwide, accounting for approximately 100 million symptomatic cases and tens of thousands of fatalities yearly. Prior infection with one serotype of dengue virus (DENV) is the greatest known risk factor for severe disease upon secondary infection with a heterologous serotype, a risk which increases as serotypes co-circulate in endemic regions. This disease risk is thought to be mediated by IgG-isotype antibodies raised during a primary infection, which poorly neutralize heterologous DENV serotypes and instead opsonize virions for uptake by FcγR-bearing cells. This antibody-dependent enhancement (ADE) of infection leads to a larger proportion of susceptible cells infected, higher viremia and greater immunopathology. We have previously characterized the induction of a serum IgA response, along with the typical IgM and IgG responses, during dengue infection, and have shown that DENV-reactive IgA can neutralize DENV and competitively antagonize IgG-mediated ADE. Here, we evaluate the potential for IgA itself to cause ADE. We show that IgG, but not IgA, mediated ADE of infection in cells expressing both FcαR and FcγRs. IgG-mediated ADE stimulated significantly higher pro-inflammatory cytokine production by primary human macrophages, while IgA did not affect, or slightly suppressed, this production. Mechanistically, we show that DENV/IgG immune complexes bind susceptible cells significantly more efficiently than DENV/IgA complexes or virus alone. Finally, we show that over the course of primary dengue infection, the expression of FcγRI (CD64) increases during the period of acute viremia, while FcγRIIa (CD32) and FcαR (CD89) expression decreases, thereby further limiting the ability of IgA to facilitate ADE in the presence of DENV. Overall, these data illustrate the distinct protective role of IgA during ADE of dengue infection and highlight the potential therapeutic and prognostic value of DENV-specific IgA.
IL-38 regulates intestinal stem cell homeostasis by inducing WNT signaling and beneficial IL-1β secretion
Authors: Dinarello Alberto , May Makenna , Amo-Aparicio Jesus , Azam Tania , Gaballa Joseph M , Marchetti Carlo , Tesoriere Annachiara , Ghirardo Rachele , Redzic Jasmina S , Webber William , Atif Shaikh M , Li Suzhao , Eisenmesser Elan Z , de Graaf Dennis M , Dinarello Charles A 
Published: April 2023

AbstractThe IL-1 Family member IL-38 has been characterized primarily as an anti-inflammatory cytokine in human and mouse models of systemic diseases. Here, we examined the role of IL-38 in the murine small intestine (SI). Immunostaining of SI revealed that IL-38 expression partially confines to intestinal stem cells. Cultures of intestinal organoids reveal IL-38 functions as a growth factor by increasing organoid size via inducing WNT3a. In contrast, organoids from IL-38 deficient mice develop more slowly. This reduction in size is likely due to downregulation of intestinal stemness markers (i.e.,Fzd5,Ephb2,Olfm4) expression compared with wild type organoids. IL-38 binding to IL-1R6 is postulated to recruit the co-receptor IL-1R9. Therefore, to analyze the molecular mechanisms of IL-38 signaling, we also examined organoids from IL-1R9 deficient mice. Unexpectedly, these organoids, although significantly smaller than wild type, respond to IL-38, suggesting that IL-1R9 is not involved in IL-38 signaling in the stem cell crypt. Nevertheless, silencing of IL-1R6 disabled the organoid response to the growth property of IL-38, thus suggesting IL-1R6 as the main receptor used by IL-38 in the crypt compartment. In organoids from wild type mice, IL-38 stimulation induced low concentrations of IL-1β which contribute to organoid growth. However, high concentrations of IL-1β have detrimental effects on the cultures that were prevented by treatment with recombinant IL-38. Overall, our data demonstrate an important regulatory function of IL-38 as a growth factor, and as an anti-inflammatory molecule in the SI, maintaining homeostasis.SignificanceThe IL-1 family member IL-38 has been characterized primarily as an anti-inflammatory cytokine for systemic diseases. Here we describe a fundamental role of IL-38 in driving intestinal stem cell differentiation through the upregulation of WNT3a and IL-1β. Our findings reveal a dual role of IL-38 in regulating intestinal functions; (a) in resting conditions IL-38 maintains intestinal homeostasis, driving WNT3a production and organoid budding, whereas (b) in highly inflamed conditions, IL-38 contributes to proper recovery, by exerting anti-inflammatory activities. Thus, we demonstrate a pivotal role of IL-38 in driving tissue turnover and maintenance of homeostasis in intestinal health.
Carbon toolmaking: responding to multiple interacting logics in carbon management
Authors: Bui Binh , Wang Zichao (Alex) , Tekathen Matthäus 
Published: April 2023

PurposeThis study examines how carbon tools, including carbon accounting and management tools, can be created, used, modified and linked with other traditional management controls to materialise and effectuate organisations’ response strategies to multiple interacting logics in carbon management and the role of sustainability managers in these processes.Design/methodology/approachThis study utilises the construct of accounting toolmaking, which refers to practices of adopting, adjusting and reconfiguring accounting tools to unfold how carbon tools are used as means to materialise responses to multiple interacting carbon management logics. It embraces a field study approach, whereby 38 sustainability managers and staff from 30 organisations in New Zealand were interviewed.FindingsThis study finds that carbon toolmaking is an important means to materialise and effectuate organisations’ response strategies to multiple interacting carbon management logics. Four response strategies are identified: separation, selective coupling, combination and hybridisation. Adopting activity involves considering the additionality, detailing, localising and cascading of carbon measures and targets and their linkage to the broader carbon management programme. In adjusting carbon tools, organisations adapt the frequency and orientation of carbon reporting, intensity of carbon monitoring and breadth of carbon information sharing. Through focusing on either procedural sequencing, assimilating, equating or integrating, toolmaking reconfigures the relationship between carbon tools and traditional management control systems. Together, these three toolmaking activities can be configured differently to construct carbon tools that are fit for purpose for each response strategy. These activities also enact certain roles on sustainability managers in the process of representing, communicating and/or transferring carbon information knowledge, which also facilitate different response strategies.Practical implicationsThe study demonstrates the various carbon toolmaking practices that allow organisations to handle the multiple interacting logics in carbon management. The findings provide suggestions for organisations on how to adopt, adjust and reconfigure carbon tools to better embed the ecological logic in organisations’ strategies and operations.Originality/valueThe authors identify how carbon toolmaking materialises and effectuates organisations’ responses to multiple interacting logics in carbon management.
Social media, echo chambers and contingency: a system theoretical approach about communication in the digital space
Authors: Rodrigues da Cunha Palmieri Emerson 
Published: April 2023

PurposeThere is a growing worry about people possibly isolating themselves in online bubbles and avoiding contact with ideas that differ from their beliefs, creating a scenario of ideological polarization. To investigate into this matter, this work aims for a reflection about the contingency of communication in social media. Does social media make the experience of communication in the digital space more contingent (providing it with more possibilities, with people accessing different contents and ideas) or less contingent (reducing the available possibilities, making people isolate themselves)?Design/methodology/approachThis is a theoretical work, constructed through bibliographical reviews. To reflect about the question that are posed, the author selected Niklas Luhmann's social systems theory to approach the concept of contingency. In addition to that, the author presented the main arguments of the debates about echo chambers and online bubbles. In the end, the author combined the two reviews together using elements of the Luhmannian theory and drew some conclusions about the initial question.FindingsThe study concluded that social media have an ambivalent potential regarding contingency in the digital space: it can both expand or reduce the available possibilities of communication, depending on criteria like topic, potential of diffusion and focus of attention. There is no one-side effect.Research limitations/implicationsThe approach at echo chambers does not reflect “the” form of contingency in social media, but “a” form. Therefore, the study cannot provide any general conclusions about the relation between contingency and social media. The digital space is a large one, and more studies are required to achieve more substantial propositions.Originality/valueThe research has an originality value both for systems theory and social media studies. First, because, as far as the author knows, no other system-theoretical argument has taken the connection between contingency and social media as a primary analysis object. Second, because of a theoretical interpretation effort, the studies of echo chambers indicate mixed results about the phenomenon of online isolation, but no attempt was made to make sense of these mixed results from a specific sociological theory. The author did that by using Luhmann's theoretical framework, which proved to be a good tool for explaining and unifying these different results on a more abstract level.
Supplementary Figure 5 from Significance of Polypyrimidine Tract–Binding Protein 1 Expression in Colorectal Cancer
Authors: Takahashi Hidekazu , Nishimura Junichi , Kagawa Yoshinori , Kano Yoshihiro , Takahashi Yusuke , Wu Xin , Hiraki Masayuki , Hamabe Atsushi , Konno Masamitsu , Haraguchi Naotsugu , Takemasa Ichiro , Mizushima Tsunekazu , Ishii Masaru , Mimori Koshi , Ishii Hideshi , Doki Yuichiro , Mori Masaki , Yamamoto Hirofumi 
Published: April 2023

<p>(A)	Strategy for detecting the CD44 variant region. Arrows indicate primers listed in Supplemental Table S1. (B) RT-PCR followed by electrophoresis for CD44 variant region in CRC cell lines. (C) Sequence analysis.</p>
Supplementary Figure 3 from Radiation Protection of the Gastrointestinal Tract and Growth Inhibition of Prostate Cancer Xenografts by a Single Compound
Authors: Alexeev Vitali , Lash Elizabeth , Aguillard April , Corsini Laura , Bitterman Avi , Ward Keith , Dicker Adam P. , Linnenbach Alban , Rodeck Ulrich 
Published: April 2023

<p>Supplementary Figure 3:	Effects of RTA 408 on prostate cancer cell survival in vitro. Cells were treated for 24 h with RTA 408 at different concentrations. Protein extracts were prepared from attached and/or detached cells to capture the full extent of apoptosis. Protein extracts from detached cells were prepared at RTA 408 concentrations {greater than or equal to}0.5 μM; solid lines above protein concentrations indicate detached cells as a source of proteins. Levels of cleaved caspase 3, cleaved PARP-1, cleaved cytokeratin-18 (M30) and cleaved caspase-8 were determined by immunoblot analyses.</p>
Supplementary Figure 1 from Radiation Protection of the Gastrointestinal Tract and Growth Inhibition of Prostate Cancer Xenografts by a Single Compound
Authors: Alexeev Vitali , Lash Elizabeth , Aguillard April , Corsini Laura , Bitterman Avi , Ward Keith , Dicker Adam P. , Linnenbach Alban , Rodeck Ulrich 
Published: April 2023

<p>Supplementary Figure 1:	Reduction in apoptosis incidence in the skin of irradiated mice. Topical radiation (30 Gy single dose) was applied to the hindlegs of mice with shielding protecting the rest of the body. RTA 408 (17.5 mg/kg) was administered 1 d prior, 1 h prior and 1 d post IR; skins were harvested 2 d post IR. Apoptotic cells were detected by TUNEL staining in tissue samples obtained 24 h after radiation exposure. The number of apoptotic cells in RTA 408-treated mice was statistically significantly reduced compared to IR + vehicle-treated mice (Student's t-test; p<0.05). DP = dermal papilla; hf = hair follicle; e = epidermis; d = dermis; m{plus minus}SD of at least six fields were evaluated.</p>
Supplementary Tables S1-S3; Supplementary Figures S1-S3; and Supplementary Materials and Methods from Mutant-Selective Irreversible EGFR Inhibitor, Naquotinib, Inhibits Tumor Growth in NSCLC Models with EGFR-Activating Mutations, T790M Mutation, and AXL Overexpression
Authors: Tanaka Hiroaki , Sakagami Hideki , Kaneko Naoki , Konagai Satoshi , Yamamoto Hiroko , Matsuya Takahiro , Yuri Masatoshi , Yamanaka Yosuke , Mori Masamichi , Takeuchi Masahiro , Koshio Hiroyuki , Hirano Masaaki , Kuromitsu Sadao 
Published: April 2023

<p>Supplementary Table S1 shows inhibitory effect of naquotinib against wild type or mutant EGFR kinase activity. Supplementary Table S2 shows inhibitory effect of naquotinib on the proliferation of Ba/F3 cells overexpressing mutant EGFRs. Supplementary Table S3 shows inhibitory effect of naquotinib against AXL kinase activity. Supplementary Figure S1 shows chemical structures of naquotinib, osimertinib, rociletinib and olmutinib. Supplementary Figure S2 shows that covalent binding between naquotinib and the Cys-797 residue of EGFR L858R/T790M was confirmed by LC-MS/MS analysis Supplementary Figure S3 shows that naquotinib did not affect the body weight of mice in the HCC827, NCI-H1975 or A431 xenograft models Supplementary Materials and Methods are as follows; 1.	Generation of Ba/F3 cells expressing mutant EGFRs 2.	Generation of PC-9AXL cells 3.	Mass spectrometry analysis of the position of the covalent bond between naquotinib and EGFR L858R/T790M 4.	Measurement of EGFR phosphorylation in NCI-H1975 tumors 5.	Antibodies 6.	In vitro cell proliferation assays</p>
Abstract 1016: Prognostic factors for overall survival, recurrence-free survival, and metastasis-free survival of colon cancer in Morocco
Authors: Agy Fatima El , Chbani Laila 
Published: April 2023

Abstract
Introduction: Colon cancer is the third most common cancer in Morocco. Its incidence and mortality rate is constantly increasing in this country. This requires the determination of clinical and molecular prognostic factors of CC in our context. Studies indicate that mutations in the RAS genes (KRAS and NRAS) represent such a factor. The aim of this study is to evaluate the prognostic impact of KRAS and NRAS mutations on overall survival (OS), recurrence-free survival (RFS) and metastasis-free survival (MFS) of CC patients.
Methods This study involved a series of 210 patients with colon cancer. The clinical and pathological data were obtained from of each patient’s files at the molecular pathology department of the CHU HASSAN II of FES. For molecular data, full RAS status was determined by direct sequencing and Q24 pyrosequencing, after extraction of DNA from formalin-fixed and paraffin-embedded tissue. The evaluation of the relationship between OS, RFS, and MFS and the molecular and clinical factors of the patients was performed by the Kaplan-Meier method and the log-rank test.
Results The average age of our patients was 57.5 ± 14.6 years. A slight male predominance was found (52.7%). 39.5% of the cases had a mutation in one of the RAS genes. Mutation of exon 2 of the KRAS gene was the most frequent with a percentage of 36.6%. The NRAS gene was mutated in 2.8% of our patients. The exon 2 mutated tumors were significantly associated with female gender (p=0.04), and left location (p=0.04) compared to the other exons. The mean OS, RFS, and MFS were 100.0%, 92.0% and 92.1% respectively. OS was significantly longer in tumors with KRAS exon 4 mutations compared to tumors with other types of RAS mutations and was also associated with right colon tumors (P=0.001), localized stages I-II (P=0.001), tumors without metastatic nodes (P=0.03), and MSI tumors (P=0.01). For RFS and MFS, localized stage and tumors without metastatic nodes were good prognostic factors (p=0.002, p=0.000). However, the type of mutated exon had no prognostic impact on either.
Conclusion In our setting right location, localized stage, absence of metastatic nodes, MSI status and mutated status of exon 4 of the KRAS gene (compared to other exons) are all predictive factors of better overall survival of colon cancer in Morocco. The type of the mutated exon of the RAS genes has no impact on RFS and MFS.
Citation Format: Fatima El Agy, Laila Chbani. Prognostic factors for overall survival, recurrence-free survival, and metastasis-free survival of colon cancer in Morocco [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1016.