bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lithium carbonate revitalizes tumor-reactive CD8+ T cells by shunting lactic acid into mitochondria
Authors: Ma Jingwei , Tang Liang , Tan Yaoyao , Xiao Jingxuan , Wei Keke , Zhang Xin , Ma Yuan , Tong Shuai , Chen Jie , Zhou Nannan , Yang Li , Lei Zhang , Li Yonggang , Lv Jiadi , Liu Junwei , Zhang Huafeng , Tang Ke , Zhang Yi , Huang Bo 
Published: January 2024

AbstractThe steady flow of lactic acid (LA) from tumor cells to the extracellular space via the monocarboxylate transporter symport system suppresses antitumor T cell immunity. However, LA is a natural energy metabolite that can be oxidized in the mitochondria and could potentially stimulate T cells. Here we show that the lactate-lowering mood stabilizer lithium carbonate (LC) can inhibit LA-mediated CD8+ T cell immunosuppression. Cytoplasmic LA increased the pumping of protons into lysosomes. LC interfered with vacuolar ATPase to block lysosomal acidification and rescue lysosomal diacylglycerol–PKCθ signaling to facilitate monocarboxylate transporter 1 localization to mitochondrial membranes, thus transporting LA into the mitochondria as an energy source for CD8+ T cells. These findings indicate that targeting LA metabolism using LC could support cancer immunotherapy.
Comparative study of NiO/CuO/Ag doped graphene based materials for reduction of nitroaromatic compounds and degradation of dye with statistical study
Authors: Pandey Gayatri , Singh Nidhi , Rajput Nitesh , Saini Mahesh Kumar , Kothari S. L. , Prasad Jagdish , Lamba Narendra Pal , Chauhan Manmohan Singh 
Published: January 2024

AbstractIn the present work, the Nickel oxide (rGO–NiO), Silver (rGO–Ag), Copper oxide (rGO–CuO) doped Graphene Oxide are reported for catalytic reactions. A comparative study for catalytic activities of these materials are performed with nitroaromatic compound 4-nitroaniline and the results are statistically studied by using univariate analysis of variance and Post Hoc Test through Statistical Package for Social Sciences and it is observed that CuO doped Graphene material is showing better catalytic activity in minimum time. So, further research has been focused on the catalytic acitivity of rGO–CuO only and it is found that it is efficient in reducing other nitro compounds also such as Picric acid and Nitrobenzene. Dye degradation of Methylene blue is also performed using CuO decorated Graphene material and significant changes were observed using UV spectroscopy. The characterization of rGO–CuO is done with Fourier-transform Infrared Spectroscopy, Powder X-ray Diffraction, Thermogravimetric Analysis, Scanning Electron Microscope and Transmission Electron Microscopy.
The trend of poisonings before and after the COVID-19 pandemic
Authors: Behnoush Amir Hossein , Bazmi Elham , Khalaji Amirmohammad , Jafari-Mehdiabad Amirhossein , Barzegari Nasrin , Dehpour Ahmad-Reza , Behnoush Behnam 
Published: January 2024

AbstractThe COVID-19 pandemic has substantially affected people and healthcare systems. One of the main challenges was the reduction and change in the pattern of non-COVID-19 diseases and conditions. Moreover, due to the mental burden of the pandemic, the trend of poisonings and abuses changed. In this study, we aimed to assess the trends of poisonings from different agents before and during the COVID-19 pandemic using the interrupted time series method. This study was conducted at one of the main Tehran referral centers for poisoning, Baharloo Hospital. Pre-COVID-19 period was defined as April 2018 to January 2020 while the COVID-19 time was from February 2020 to March 2022. The total number of monthly poisoning cases in addition to eight categories of drugs/substances/agents were identified, including drugs (such as psychiatric drugs, cardiovascular drugs, and analgesics), opioids, stimulants, methanol, ethanol, cannabis, pesticides, and carbon monoxide. Interrupted time series analysis was performed to compare the pre-pandemic trend of total monthly cases from each category in addition to the proportion (%) of each one. In total, 13,020 cases were poisoned during the study period, among which 6088 belonged to the pre-pandemic period and 6932 were admitted during the COVID-19 era. There was no significant difference in terms of demographic characteristics of patients before and during the pandemic (p-value > 0.05). At the beginning of the pandemic, there was a sudden fall in the number of poisoning patients (− 77.2 cases/month, p-value = 0.003), however, there was a significant increasing trend during the COVID time (3.9 cases/month, p-value = 0.006). Most of the categories had a sharp decrease at the beginning of the pandemic except for methanol and ethanol which had increases, although not significant. Cannabis also had a significant change in slope (− 0.6 cases/month, p-value = 0.016), in addition to the sudden decrease at the beginning of the pandemic (− 10 cases/month, p-value = 0.007). Regarding the proportion of each category from total monthly poisoning cases, methanol, and ethanol had immediate rises of 4.2% per month and 10.1% per month, respectively (both significant). The pandemic had significant effects on the pattern of poisonings from different agents in Iran, the most important of which were alcohol (ethanol and methanol). These differences had policy implications that can be helpful for policymakers and healthcare systems in combating similar situations in the future.
Dose-dependent reduction of somatic expansions but not Htt aggregates by di-valent siRNA-mediated silencing of MSH3 in HdhQ111 mice
Authors: Driscoll Rachelle , Hampton Lucas , Abraham Neeta A. , Larigan J. Douglas , Joseph Nadine F. , Hernandez-Vega Juan C. , Geisler Sarah , Yang Fu-Chia , Deninger Matthew , Tran David T. , Khatri Natasha , Godinho Bruno M. D. C. , Kinberger Garth A. , Montagna Daniel R. , Hirst Warren D. , Guardado Catherine L. , Glajch Kelly E. , Arnold H. Moore , Gallant-Behm Corrie L. , Weihofen Andreas 
Published: January 2024

AbstractHuntington's disease (HD) is a progressive neurodegenerative disorder caused by CAG trinucleotide repeat expansions in exon 1 of the HTT gene. In addition to germline CAG expansions, somatic repeat expansions in neurons also contribute to HD pathogenesis. The DNA mismatch repair gene, MSH3, identified as a genetic modifier of HD onset and progression, promotes somatic CAG expansions, and thus presents a potential therapeutic target. However, what extent of MSH3 protein reduction is needed to attenuate somatic CAG expansions and elicit therapeutic benefits in HD disease models is less clear. In our study, we employed potent di-siRNAs to silence mouse Msh3 mRNA expression in a dose-dependent manner in HdhQ111/+ mice and correlated somatic Htt CAG instability with MSH3 protein levels from simultaneously isolated DNA and protein after siRNA treatment. Our results reveal a linear correlation with a proportionality constant of ~ 1 between the prevention of somatic Htt CAG expansions and MSH3 protein expression in vivo, supporting MSH3 as a rate-limiting step in somatic expansions. Intriguingly, despite a 75% reduction in MSH3 protein levels, striatal nuclear HTT aggregates remained unchanged. We also note that evidence for nuclear Msh3 mRNA that is inaccessible to RNA interference was found, and that MSH6 protein in the striatum was upregulated following MSH3 knockdown in HdhQ111/+ mice. These results provide important clues to address critical questions for the development of therapeutic molecules targeting MSH3 as a potential therapeutic target for HD.
The nucleolar shell provides anchoring sites for DNA untwisting
Authors: Fukute Jumpei , Maki Koichiro , Adachi Taiji 
Published: January 2024

AbstractDNA underwinding (untwisting) is a crucial step in transcriptional activation. DNA underwinding occurs between the site where torque is generated by RNA polymerase (RNAP) and the site where the axial rotation of DNA is constrained. However, what constrains DNA axial rotation in the nucleus is yet unknown. Here, we show that the anchorage to the nuclear protein condensates constrains DNA axial rotation for DNA underwinding in the nucleolus. In situ super-resolution imaging of underwound DNA reveal that underwound DNA accumulates in the nucleolus, a nuclear condensate with a core–shell structure. Specifically, underwound DNA is distributed in the nucleolar core owing to RNA polymerase I (RNAPI) activities. Furthermore, underwound DNA in the core decreases when nucleolar shell components are prevented from binding to their recognition structure, G-quadruplex (G4). Taken together, these results suggest that the nucleolar shell provides anchoring sites that constrain DNA axial rotation for RNAPI-driven DNA underwinding in the core. Our findings will contribute to understanding how nuclear protein condensates make up constraints for the site-specific regulation of DNA underwinding and transcription.
The relationship between intimate partner behaviour control and impulsivity among college students: the chain mediating effect of autonomy needs satisfaction and intimacy quality
Authors: Lan Ruiming , Shen Zifeng , Lian Rong 
Published: January 2024

AbstractUsing the Intimate Partner Behaviour Control Scale, the Autonomy Needs Questionnaire, the Intimacy Quality Questionnaire, and the Chinese version of the Brief Barratt Impulsiveness Scale, we conducted a survey of 416 college students (204 males and 212 females) with a mean age of 24.99 (SD = 7.94) years. The aim of this research was to explore the relationship between intimate partner behaviour control and impulsivity with a focus on the roles of autonomy needs satisfaction and intimacy quality in the context of college students in romantic relationships. The findings indicated that (1) intimate partner behaviour control significantly and positively predicts impulsivity among college students; (2) autonomy needs satisfaction plays a mediating role in the relationship between intimate partner behaviour control and impulsivity among college students; (3) intimacy quality also plays a mediating role in the relationship between intimate partner behaviour control and impulsivity among college students; (4) autonomy needs satisfaction and intimacy quality jointly play a chain mediating role in the relationship between intimate partner behaviour control and impulsivity among college students. These results highlight the close relationship between intimate partner behaviour control and impulsivity, in which context autonomy needs and intimacy quality play a vital role. The findings of this research offer practical insights for mental health practitioners with regard to preventing and intervening in impulsive behaviour among college students as well as guidance for policy plans that aim to promote healthy relationships and prevent intimate partner violence.
3D inversion of magnetic gradient data based on equivalent source weighting method
Authors: Huang Shuanglong , Qiu Jing , Li Mingyu , Sun Hexuan , Zhang Shunyu 
Published: January 2024

3D magnetic inversion is an important method for detecting underwater or underground magnetic objects, which can obtain the physical parameters and geometric features of the target. In order to solve the problem of smooth inversion results of L2 norm regularization, this paper proposes a three-dimensional inversion method of magnetic gradient data based on equivalent source weighting. First, the center position of the magnetic object is estimated using the correlation imaging method, and then the equivalent source weighting function is constructed based on the acquired center position. The weights are calculated according to the distance from the grid to the center of the magnetic object. The further away the grid is, the higher weight will be given. The Euclidean distance and Chebyshev distance are used for calculating the weights of grids. Finally, the equivalent source weighting function is added to the total objective function and solved by conjugate gradient method. Simulation experiments show that the equivalent source weighting function can reduce the root-mean-square error of the inversion results and improve the structural similarity. Compared with the Euclidean distance, the inversion result of the edges and corners of cubic magnetic body model is better when weighted with the Chebyshev distance. The proposed method does not require iterative solving and can avoid generating too smooth results, which improves the inversion accuracy.
Nation Branding in Latin America: Repositioning Brazil to Reset Its Brand Image
Authors: Ocke Marco , Braga Debora Cordeiro 
Published: January 2024

Summary
By performing country brand initiatives and hosting mega sporting events as international promotional tools, Brazil, the largest economy in Latin America, has tried to leverage its brand awareness as a promising hub for investment for a great variety of sectors and add new attributes to the country’s image, such as a strong, innovative and sustainable economy. However, the country has accumulated instability and turbulence over the years, which has discredited reputation-building efforts. The lack of public financial management, economic crisis associated with widespread corruption, inappropriate responses to the COVID-19 pandemic and lack of environmental management affected the country’s image negatively. Currently, the relaunch of “Marca Brasil” represents an effort to reset its brand image based on a repositioning strategy oriented to stand the country as a protagonist on the global stage, adding value to how the country is perceived.

Information
© The Authors 2024
The first case of methotrexate-associated lymphoproliferative disorder in the sacrum: a case report
Authors: Yamaguchi Yuichi , Morimoto Tadatsugu , Toda Yu , Tsukamoto Masatsugu , Yoshihara Tomohito , Hirata Hirohito , Kobayashi Takaomi , Mawatari Masaaki 
Published: January 2024

Abstract
Methotrexate (MTX) is a drug used for treating rheumatoid arthritis. Recently, the reported incidence of methotrexate-associated lymphoproliferative disease (MTX-LPD) has increased, especially in Japan. Extranodal involvement is observed in half of MTX-LPD cases. However, only a few spinal lesions have been reported, with none in the sacrum. Additionally, Epstein-Barr virus (EBV) infection has also been implicated in the pathogenesis of MTX-LPD. Herein, we describe the case of a 74-year-old woman with MTX-LPD in the sacral spine who complained of severe back pain and nocturnal pain. Radiographs revealed a tumour on the right wing of the sacrum and a positive EBV immunoglobulin G antibody titre. MTX-LPD was suspected based on imaging findings and a history of MTX administration. A pathological examination was performed on the CT-guided biopsy specimen. The histopathological diagnosis was MTX-LPD, and MTX was discontinued. Three months after MTX administration ended, the tumour tended to shrink, and 1 year later, significant tumour shrinkage was observed. This experience suggests that MTX-LPD can be treated by discontinuing MTX administration. Therefore, early and accurate diagnosis is required, as is avoiding unnecessary treatment such as surgery. MTX-LPD should be considered, especially in spinal origin tumours in EBV-infected patients on MTX.
OP26 Programmable probiotic local delivery of anti-TNF-α nanobody to alleviate DSS-induced colitis
Authors: Kang G , Zhu Z , Gao M , Wang L , Cao X , Liu X , Huang H 
Published: January 2024

Abstract

Background
Biological agents represented by Infliximab have brought a milestone leap forward in the treatment of IBD. However, the overall response rate of anti-TNF-α antibodies in clinical practice is just 40-60% and the adverse reactions caused by the lack of gut-selective further limit its clinical application. Systemic effects of intravenous administration may be an essential cause of paradoxical response and immune adaptive succession (secondary loss of response). Rapid advances in synthetic biology allow targeted delivery of antibody drugs via engineered probiotics to improve bioavailability while reducing the risk of systemic effects.

Methods
Here, we developed an engineered probiotic (EcN-VHH2M3) that intelligently responds to the inflammatory marker thiosulfate and produces the anti-TNF-α nanobody VHH2M3. At the same time, controlled release of anti-TNF-α biologic was achieved in response to colitis marker nitrate and quorum sensing mechanism. The dextran sulfate sodium (DSS)-induced colitis model was used to explore the feasibility of EcN-VHH2M3 for the IBD treatment. The disease activity index of the subject animals was detected and evaluated. The colon length and spleen weight were measured and HE staining. Real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) are used to detect cytokine expression levels in colon tissue.

Results
In vivo results showed that EcN-VHH2M3 group significantly reduced disease activity index and restored intestinal mucosal barrier compared with control group. DSS administration resulted in hyperemia, ulceration, and thickening of the bowel wall, which were reduced in the treatment group. In addition, spleen weight and colon length were close to the control group. EcN-VHH2M3 treatments significantly decreased the expression levels of pro-inflammatory cytokines IL-1β, TNF-α, and IFN-γ, while the expression of anti-inflammatory cytokines IL-10 and TGF-β was enhanced.

Conclusion
Inflammatory microenvironment-responsive programmable probiotics effectively alleviate DSS-induced colitis in mice and restore the intestinal mucosal barrier through the targeted release of anti-TNF-α nanobody. This study preliminarily confirmed that the controlled intestinal release of anti-TNF biologics by engineered probiotics provides a promising paradigm for IBD treatment with non-gut-selective antibodies.
OP29 Haematopoietic stem cell gene therapy as a treatment for severe Crohn’s Disease associated with pathogenic NOD2 genetic variants
Authors: Enjalbert F , del Mar Masdeu M , Zabinski T , Narean J S , Elavazhagan S , Whiting C , Pennucci V , Luiz A , Du L , Recchi C , Cattoni M , Heal P , Gaspar B , Mavilio F , Sagoo P 
Published: January 2024

Abstract

Background
Pathogenic variants of the NOD2 (nucleotide-binding oligomerization domain containing protein 2) gene demonstrate the strongest genetic association to Crohn’s inflammatory bowel disease (CD), with mounting evidence linking NOD2 deficiency with poor clinical outcome. CD patients with NOD2 variants, particularly carriers of more than one risk allele, frequently present an aggressive, fistulizing and fibrostenotic disease, requiring multiple surgical resections. NOD2-deficiency is implicated to drive CD pathogenesis through failure of gut innate immunity to resolve bacterial infections and by loss of tissue homeostasis within the intestinal microenvironment. Here we present preclinical data on OTL-104, an autologous haematopoietic stemcell gene therapy (HSC-GT) which aims to stably restore NOD2 expression in gut resident macrophages, to correct immune dysfunction linked to NOD2-deficient CD pathogenesis.

Methods
We used in vitro and in vivo models of NOD2 deficiency to demonstrate the mechanism of action and the efficacy of OTL-104 autologous HSC-GT.

Results
NOD2KO human myeloid cells differentiated in vitro from CRISPR-generated NOD2KO CD34+ HSCs are unable to mount a proinflammatory cytokine response to MDP stimulation. Similarly, myeloid cells differentiated from CD34+ cells obtained from peripheral blood of genetically characterized NOD2-deficient CD patients, are also refractory to MDP stimulation and unable to generate a normal cytokine response profile. In both NOD2 deficient CD34+ derived monocyte models, transduction with a lentiviral vector (LVV) expressing NOD2 fully restores NOD2-dependent cytokine and chemokine responses, restoring an immune profile that is comparable to monocytes derived from CD34+ cells from NOD2 wild-type healthy donors (Figure 1).
Transplantation of lineage negative (Lin-) haematopoietic stem/progenitor cells (HSPCs) transduced with the OTL-104 LVV in NOD2KO mice was used as an in vivo model of gene therapy for CD. Compared to WT mice, NOD2KO mice fail to release systemic inflammatory mediators and recruit myeloid cells in response to MDP administration. Transplantation of transduced Lin- HSPCs restores MDP-induced systemic release of IL-6 and CXCL1 as well as innate mobilization of monocyte/macrophage cells and gut associated gene expression. Key to our therapeutic approach, histopathological analysis of intestinal lamina propria from transplanted mice shows a normal biodistribution and physiological NOD2 gene expression in tissue resident cells.

Conclusion
These results confirm the impact of NOD2 deficiency in primary immune activation and demonstrates the therapeutic potential of OTL-104 HSC-GT for long-term correction of NOD2-deficient CD.
OP30 Endothelial cell-mediated smooth muscle hyperplasia in Crohn’s disease intestinal strictures: Caveolin 1 as a potential therapeutic target
Authors: Acharjee A , Shivaji U N , Santacroce G , Jeffery L , Amamou A , Reynolds G , Majumder S , Akiror S , Zardo D , Gkoutos G V , Ghosh S , Iacucci M 
Published: January 2024

Abstract

Background
Intestinal stricture is a severe and common complication of Crohn’s disease (CD). Current therapies offer limited success and surgery is often needed. Smooth muscle hyperplasia and hypertrophy play a key role in CD stricture development. This study explores the transcriptomic features of fibrostenotic CD, focusing on the endothelial contribution to smooth muscle changes within intestinal strictures.

Methods
9 CD patients undergoing surgery for fibrotic strictures were prospectively enrolled. Dissected samples from the stricture and the adjacent proximal and distal non-strictured areas were obtained from fresh specimens collected directly from the operating theatre. RNA was extracted from all samples for bulk-transcriptomic analysis. Differentially expressed genes (adj. p-value &lt;0.05) were identified and pathway enrichment analysis pinpointed relevant pathways. Subsequently, single-cell RNA sequencing (scRNAseq) analysis was performed using the 10x Chromium Controller® platform. A total of 31.195 cells were sequenced and bioinformatic analysis revealed 13 distinct clusters based on the expression of key lineage target genes. To better characterise the nature of clusters expressing stromal like markers and positioned closely in the UMAP plot, a further subclustering was performed. This resulted in 5 groups, including plasma cells, endothelial cells, fibroblasts, epithelial cells and dendritic like cells.

Results
Bulk-transcriptomic analysis identified 81 genes differentially expressed in strictures compared to both proximal and distal regions. Notably, genes associated with leukocyte and macrophage recruitment and chemotaxis, namely Platelet and Endothelial Cell Adhesion Molecule 1 (PECAM1), C-C motif Chemokine Ligand 2 (CCL2), and Endothelin Receptor Type B (EDNRB), resulted overexpressed in strictures. scRNAseq identified a distinct subset of endothelial cells (CD34+, PECAM1+). Caveolin 1 (CAV1), a gene encoding for a structural protein predominantly expressed in smooth muscle cell plasma membrane invaginations, was exclusively up-regulated in endothelial cells of ileal stricture samples. Previous research linked CAV1 to smooth muscle proliferation and fibrosis in various organs.

Conclusion
This study highlights the pivotal role of endothelial cells in CD strictures. The transcriptomic analysis shows the involvement of inflammatory targets featured genes involved in transendothelial immune cell migration. Furthermore, the up-regulation of CAV1 in endothelial cells within stricture segments suggests a mechanistic connection between endothelial cells and smooth muscle hyperplasia in intestinal strictures. CAV1 holds promise as a potential therapeutic target in fibrostenotic CD.