bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunoglobulin and T cell receptor repertoire changes induced by a prototype vaccine against Chagas disease in naïve rhesus macaques
Authors: Dumonteil Eric , Tu Weihong , Desale Hans , Goff Kelly , Marx Preston , Ortega-Lopez Jaime , Herrera Claudia 
Published: June 2024

Abstract
Background
A vaccine against Trypanosoma cruzi, the agent of Chagas disease, would be an excellent additional tool for disease control. A recombinant vaccine based on Tc24 and TSA1 parasite antigens was found to be safe and immunogenic in naïve macaques.

Methods
We used RNA-sequencing and performed a transcriptomic analysis of PBMC responses to vaccination of naïve macaques after each vaccine dose, to shed light on the immunogenicity of this vaccine and guide the optimization of doses and formulation. We identified differentially expressed genes and pathways and characterized immunoglobulin and T cell receptor repertoires.

Results
RNA-sequencing analysis indicated a clear transcriptomic response of PBMCs after three vaccine doses, with the up-regulation of several immune cell activation pathways and a broad non-polarized immune profile. Analysis of the IgG repertoire showed that it had a rapid turnover with novel IgGs produced following each vaccine dose, while the TCR repertoire presented several persisting clones that were expanded after each vaccine dose.

Conclusions
These data suggest that three vaccine doses may be needed for optimum immunogenicity and support the further evaluation of the protective efficacy of this vaccine.
High stress hyperglycemia ratio predicts adverse clinical outcome in patients with coronary three-vessel disease: a large-scale cohort study
Authors: Qiao Zheng , Bian Xiaohui , Song Chenxi , Zhang Rui , Yuan Sheng , Lin Zhangyu , Zhu Chenggang , Liu Qianqian , Ma Wenjun , Dou Kefei 
Published: June 2024

Abstract
Background
Coronary three-vessel disease (CTVD) accounts for one-third of the overall incidence of coronary artery disease, with heightened mortality rates compared to single-vessel lesions, including common trunk lesions. Dysregulated glucose metabolism exacerbates atherosclerosis and increases cardiovascular risk. The stress hyperglycemia ratio (SHR) is proposed as an indicator of glucose metabolism status but its association with cardiovascular outcomes in CTVD patients undergoing percutaneous coronary intervention (PCI) remains unclear.

Methods
10,532 CTVD patients undergoing PCI were consecutively enrolled. SHR was calculated using the formula: admission blood glucose (mmol/L)/[1.59×HbA1c (%)–2.59]. Patients were divided into two groups (SHR Low and SHR High) according to the optimal cutoff value of SHR. Multivariable Cox regression models were used to assess the relationship between SHR and long-term prognosis. The primary endpoint was cardiovascular (CV) events, composing of cardiac death and non-fatal myocardial infarction (MI).

Results
During the median follow-up time of 3 years, a total of 279 cases (2.6%) of CV events were recorded. Multivariable Cox analyses showed that high SHR was associated with a significantly higher risk of CV events [Hazard Ratio (HR) 1.99, 95% Confidence interval (CI) 1.58–2.52, P < 0.001). This association remained consistent in patients with (HR 1.50, 95% CI 1.08–2.10, P = 0.016) and without diabetes (HR 1.97, 95% CI 1.42–2.72, P < 0.001). Additionally, adding SHR to the base model of traditional risk factors led to a significant improvement in the C-index, net reclassification and integrated discrimination.

Conclusions
SHR was a significant predictor for adverse CV outcomes in CTVD patients with or without diabetes, which suggested that it could aid in the risk stratification in this particular population regardless of glucose metabolism status.
cFLIP in the molecular regulation of astroglia-driven neuroinflammation in experimental glaucoma
Authors: Yang Xiangjun , Zeng Qun , İnam Maide Gözde , İnam Onur , Lin Chyuan-Sheng , Tezel Gülgün 
Published: June 2024

Abstract
Background
Recent experimental studies of neuroinflammation in glaucoma pointed to cFLIP as a molecular switch for cell fate decisions, mainly regulating cell type-specific caspase-8 functions in cell death and inflammation. This study aimed to determine the importance of cFLIP for regulating astroglia-driven neuroinflammation in experimental glaucoma by analyzing the outcomes of astroglia-targeted transgenic deletion of cFLIP or cFLIPL.

Methods
Glaucoma was modeled by anterior chamber microbead injections to induce ocular hypertension in mouse lines with or without conditional deletion of cFLIP or cFLIPL in astroglia. Morphological analysis of astroglia responses assessed quantitative parameters in retinal whole mounts immunolabeled for GFAP and inflammatory molecules or assayed for TUNEL. The molecular analysis included 36-plexed immunoassays of the retina and optic nerve cytokines and chemokines, NanoString-based profiling of inflammation-related gene expression, and Western blot analysis of selected proteins in freshly isolated samples of astroglia.

Results
Immunoassays and immunolabeling of retina and optic nerve tissues presented reduced production of various proinflammatory cytokines, including TNFα, in GFAP/cFLIP and GFAP/cFLIPL relative to controls at 12 weeks of ocular hypertension with no detectable alteration in TUNEL. Besides presenting a similar trend of the proinflammatory versus anti-inflammatory molecules displayed by immunoassays, NanoString-based molecular profiling detected downregulated NF-κB/RelA and upregulated RelB expression of astroglia in ocular hypertensive samples of GFAP/cFLIP compared to ocular hypertensive controls. Analysis of protein expression also revealed decreased phospho-RelA and increased phospho-RelB in parallel with an increase in caspase-8 cleavage products.

Conclusions
A prominent response limiting neuroinflammation in ocular hypertensive eyes with cFLIP-deletion in astroglia values the role of cFLIP in the molecular regulation of glia-driven neuroinflammation during glaucomatous neurodegeneration. The molecular responses accompanying the lessening of neurodegenerative inflammation also seem to maintain astroglia survival despite increased caspase-8 cleavage with cFLIP deletion. A transcriptional autoregulatory response, dampening RelA but boosting RelB for selective expression of NF-κB target genes, might reinforce cell survival in cFLIP-deleted astroglia.
Motivations for using misoprostol for abortion outside the formal healthcare system in Colombia: a qualitative study of women seeking postabortion care in Bogotá and the Coffee Axis
Authors: Ortiz Juliette , Blades Nakeisha , Prada Elena 
Published: June 2024

Abstract
Background
In 2006, a Constitutional Court ruling partially decriminalized abortion in Colombia, allowing the procedure in cases of rape, risk to the health or life of the woman, and fetal malformations incompatible with life. Despite this less prohibitive law, some women and pregnant people preferred self-managing their abortions outside the formal healthcare system, often without accurate information. In 2018, we undertook a study to understand what motivated women to self-manage using medications that they acquired informally. Colombia has since adopted a progressive law in 2022, permitting abortion on request through the 24th week of pregnancy. However, the implementation of this law is still underway. Examining the reasons why women chose to informally self-manage an abortion after 2006 may not only highlight how barriers to legal services persisted at that time, but also could inform strategies to increase knowledge of the current abortion law and improve access to services going forward.

Methods
In-depth interviews were conducted in 2018 with 47 women aged 18 and older who used misoprostol obtained outside of health facilities to induce an abortion, and who were receiving postabortion care in two private clinics. Interviews explored what women knew about the 2006 abortion law which was then in effect, and the reasons why they preferred informal channels for abortion care over formal healthcare services.

Results
Women’s motivations to use misoprostol obtained outside the formal healthcare system were influenced by lack of trust in the healthcare system along with incomplete and inaccurate knowledge of the abortion law. Conversely, women considered misoprostol obtained outside the healthcare system to be effective, affordable, and easier to access.

Conclusions
Obtaining misoprostol outside the formal healthcare system offered a more accessible and appealing prospect for some women given fears of legal repercussion and stigma toward abortion. Though this preference will likely continue despite the more liberal abortion law, strategies should be implemented to broaden knowledge of the recent change in law and to combat misinformation and stigma. This would support knowledge of and access to legal abortion for those who wish to avail themselves of these services.
Ac2-26 reduced the liver injury after cardiopulmonary bypass in rats via AKT1/GSK3β/eNOS pathway
Authors: Xing Xi-chun , Liu Zi-ying , Yang Qing , Jia Bao-wei , Qiu Lin , Zhang Lu-lu , Gao Wei 
Published: June 2024

Abstract
Objective
About 10% of patients after cardiopulmonary bypass (CPB) would undergo acute liver injury, which aggravated the mortality of patients. Ac2-26 has been demonstrated to ameliorate organic injury by inhibiting inflammation. The present study aims to evaluate the effect and mechanism of Ac2-26 on acute liver injury after CPB.

Methods
A total of 32 SD rats were randomized into sham, CPB, Ac, and Ac/AKT1 groups. The rats only received anesthesia, and rats in other groups received CPB. The rats in Ac/AKT1 were pre-injected with the shRNA to interfere with the expression of AKT1. The rats in CPB were injected with saline, and rats in Ac and Ac/AKT1 groups were injected with Ac2-26. After 12 h of CPB, all the rats were sacrificed and the peripheral blood and liver samples were collected to analyze. The inflammatory factors in serum and liver were detected. The liver function was tested, and the pathological injury of liver tissue was evaluated.

Results
Compared with the sham group, the inflammatory factors, liver function, and pathological injury were worsened after CPB. Compared with the CPB group, the Ac2-26 significantly decreased the pro-inflammatory factors and increased the anti-inflammatory factor, improved liver function, and ameliorated the pathological injury. All the therapeutic effects of Ac2-26 were notably attenuated by the shRNA of AKT1. The Ac2-26 increased the GSK3β and eNOS, and this promotion was inhibited by the shRNA.

Conclusion
The Ac2-26 significantly treated the liver injury, inhibited inflammation, and improved liver function. The effect of Ac2-26 on liver injury induced by CPB was partly associated with the promotion of AKT1/GSK3β/eNOS.
Greenhouse gas fluxes of different land uses in mangrove ecosystem of East Kalimantan, Indonesia
Authors: Arifanti Virni Budi , Candra Randi Ade , Putra Chandra Agung Septiadi , Asyhari Adibtya , Gangga Adi , Ritonga Rasis Putra , Ilman Muhammad , Anggoro Aji W. , Novita Nisa 
Published: June 2024

Abstract
Background
Mangrove ecosystems exhibit significant carbon storage and sequestration. Its capacity to store and sequester significant amounts of carbon makes this ecosystem very important for climate change mitigation. Indonesia, owing to the largest mangrove cover in the world, has approximately 3.14 PgC stored in the mangroves, or about 33% of all carbon stored in coastal ecosystems globally. Unfortunately, our comprehensive understanding of carbon flux is hampered by the incomplete repertoire of field measurement data, especially from mangrove ecosystem-rich regions such as Indonesia and Asia Pacific. This study fills the gap in greenhouse gases (GHGs) flux studies in mangrove ecosystems in Indonesia by quantifying the soil CO2 and CH4 fluxes for different land use types in mangrove ecosystems, i.e., secondary mangrove (SM), restored mangrove (RM), pond embankment (PE) and active aquaculture pond (AP). Environmental parameters such as soil pore salinity, soil pore water pH, soil temperature, air temperature, air humidity and rainfall are also measured.

Results
GHG fluxes characteristics varied between land use types and ecological conditions. Secondary mangrove and exposed pond embankment are potential GHG flux sources (68.9 ± 7.0 and 58.5 ± 6.2 MgCO2e ha− 1 yr− 1, respectively). Aquaculture pond exhibits the lowest GHG fluxes among other land use types due to constant inundation that serve as a barrier for the release of GHG fluxes to the atmosphere. We found weak relationships between soil CO2 and CH4 fluxes and environmental parameters.

Conclusions
The data and information on GHG fluxes from different land use types in the mangrove ecosystem will be of importance to accurately assess the potential of the mangrove ecosystem to sequester and emit GHGs. This will support the GHG emission reduction target and strategy that had been set up by the Indonesian Government in its Nationally Determined Contributions (NDC) and Indonesia’s 2030 Forest and Other Land Use (FOLU) Net Sink.
What aspects of the pandemic had the greatest impact on adolescent mental health: duration of lockdown or subjective experience?
Authors: Fujimoto Hiroko , Heywood Anita , Maston Kate , Brown Lyndsay , Bartholomew Alexandra , Werner-Seidler Aliza , Christensen Helen , Batterham Philip J. 
Published: June 2024

Abstract
Background
The COVID-19 pandemic negatively impacted global mental health, with adolescents experiencing disproportionate effects. Limited research has explored the impact of different pandemic restrictions on adolescent mental health, and only a few studies have examined the longer-term impacts of the pandemic on adolescent mental health. These investigations are crucial for informing public health policies, particularly the integration of mental health care in future public health emergencies.

Methods
This study aimed to investigate the impact of lockdown duration and the impact of adolescents’ subjective experiences of the pandemic on their wellbeing, internalising symptoms, and externalising symptoms. Australian adolescents (N = 1,001, mean age = 14.2 years) completed a baseline survey in 2021, shortly after pandemic lockdowns were lifted (Time 1), and a follow-up survey approximately 12 months later (Time 2). Predictors of interest were the total duration of COVID-19 lockdowns across 2020–2021, and adolescents’ subjective experiences of the pandemic on their social connections, learning, technology use and family relationships. A range of covariates were included in analyses to examine subgroup differences.

Results
Linear mixed-effects models indicated that total duration of the lockdown was not associated with any of the outcomes at Time 1 or Time 2 (all ps > 0.017). Negative subjective experience of the pandemic on learning was associated with greater externalising symptoms at both Time 1 (t = 5.17, df = 980, p <.001) and Time 2 (t = 2.72, df = 708, p =.007). Negative subjective experience of the pandemic on social connection was associated with greater internalising symptoms at Time 2 only (t = 3.20, df = 709, p =.001). Negative subjective experience of the pandemic on family relationships or technology use was not associated with any of the outcomes at Time 1 or Time 2 (all ps > 0.017).

Conclusions
Adolescents’ negative subjective experience of the pandemic on learning and social connections was associated with greater internalising and externalising symptoms after the lockdown had been lifted. Duration of lockdowns was not associated with any of the primary outcomes. During future public health emergencies, mental health interventions should be tailored to assist adolescents to adapt to new learning environments, and to build and maintain social connections.
PI3Kγ inhibition combined with DNA vaccination unleashes a B-cell-dependent antitumor immunity that hampers pancreatic cancer
Authors: Curcio Claudia , Mucciolo Gianluca , Roux Cecilia , Brugiapaglia Silvia , Scagliotti Alessandro , Guadagnin Giorgia , Conti Laura , Longo Dario , Grosso Demis , Papotti Mauro Giulio , Hirsch Emilio , Cappello Paola , Varner Judith A. , Novelli Francesco 
Published: June 2024

AbstractPhosphoinositide-3-kinase γ (PI3Kγ) plays a critical role in pancreatic ductal adenocarcinoma (PDA) by driving the recruitment of myeloid-derived suppressor cells (MDSC) into tumor tissues, leading to tumor growth and metastasis. MDSC also impair the efficacy of immunotherapy. In this study we verify the hypothesis that MDSC targeting, via PI3Kγ inhibition, synergizes with α-enolase (ENO1) DNA vaccination in counteracting tumor growth.Mice that received ENO1 vaccination followed by PI3Kγ inhibition had significantly smaller tumors compared to those treated with ENO1 alone or the control group, and correlated with i) increased circulating anti-ENO1 specific IgG and IFNγ secretion by T cells, ii) increased tumor infiltration of CD8+ T cells and M1-like macrophages, as well as up-modulation of T cell activation and M1-like related transcripts, iii) decreased infiltration of Treg FoxP3+ T cells, endothelial cells and pericytes, and down-modulation of the stromal compartment and T cell exhaustion gene transcription, iv) reduction of mature and neo-formed vessels, v) increased follicular helper T cell activation and vi) increased “antigen spreading”, as many other tumor-associated antigens were recognized by IgG2c “cytotoxic” antibodies. PDA mouse models genetically devoid of PI3Kγ showed an increased survival and a pattern of transcripts in the tumor area similar to that of pharmacologically-inhibited PI3Kγ-proficient mice. Notably, tumor reduction was abrogated in ENO1 + PI3Kγ inhibition-treated mice in which B cells were depleted.These data highlight a novel role of PI3Kγ in B cell-dependent immunity, suggesting that PI3Kγ depletion strengthens the anti-tumor response elicited by the ENO1 DNA vaccine.
Recalcitrant intussusception: exploring potential associations with Helicobacter pylori infection - a case report and literature review
Authors: Wang Kuan-Chieh , Chu Chun-Hao , Chiang Che-Ming , Zeng Fu-Ruei , Huang Ching-Wen , Lin Chien-Ming 
Published: June 2024

Abstract
Background
Intussusception, a common cause of abdominal pain in children, often lacks clear underlying causes and is mostly idiopathic. Recurrence, though rare, raises clinical concerns, with rates escalating after each episode. Factors like pathological lead points and Henoch-Schönlein purpura (HSP) are associated with recurrent cases. On the other hand, the prevalence of Helicobacter pylori (H. pylori), often asymptomatic, in children has been declining. Although its infection is reported to be linked with HSP, its role in recurrent intussusception remains unexplored. Further research is needed to understand the interplay among H. pylori (culprit pathogen), HSP (trigger), and intractable intussusception so as to develop effective management strategies.

Case presentation
A two-year-old girl experienced four atypical episodes of intussusception at distinct locations, which later coincided with HSP. Despite treatment with steroids, recurrent intussusception persisted, suggesting that HSP itself was not a major cause for intractable presentations. Subsequent identification of H. pylori infection and treatment with triple therapy resulted in complete resolution of her recalcitrant intussusception.

Conclusion
This instructive case underscored a sequence wherein H. pylori infection triggered HSP, subsequently resulting in recurrent intussusception. While H. pylori infection is not common in young children, the coexistence of intractable intussusception and steroid-resistant recurrent HSP necessitates consideration of H. pylori infection as a potential underlying pathogen.
Bayesian genome-wide TWAS with reference transcriptomic data of brain and blood tissues identified 141 risk genes for Alzheimer’s disease dementia
Authors: Guo Shuyi , Yang Jingjing 
Published: June 2024

Abstract
Background
Transcriptome-wide association study (TWAS) is an influential tool for identifying genes associated with complex diseases whose genetic effects are likely mediated through transcriptome. TWAS utilizes reference genetic and transcriptomic data to estimate effect sizes of genetic variants on gene expression (i.e., effect sizes of a broad sense of expression quantitative trait loci, eQTL). These estimated effect sizes are employed as variant weights in gene-based association tests, facilitating the mapping of risk genes with genome-wide association study (GWAS) data. However, most existing TWAS of Alzheimer's disease (AD) dementia are limited to studying only cis-eQTL proximal to the test gene. To overcome this limitation, we applied the Bayesian Genome-wide TWAS (BGW-TWAS) method to leveraging both cis- and trans- eQTL of brain and blood tissues, in order to enhance mapping risk genes for AD dementia.

Methods
We first applied BGW-TWAS to the Genotype-Tissue Expression (GTEx) V8 dataset to estimate cis- and trans- eQTL effect sizes of the prefrontal cortex, cortex, and whole blood tissues. Estimated eQTL effect sizes were integrated with the summary data of the most recent GWAS of AD dementia to obtain BGW-TWAS (i.e., gene-based association test) p-values of AD dementia per gene per tissue type. Then we used the aggregated Cauchy association test to combine TWAS p-values across three tissues to obtain omnibus TWAS p-values per gene.

Results
We identified 85 significant genes in prefrontal cortex, 82 in cortex, and 76 in whole blood that were significantly associated with AD dementia. By combining BGW-TWAS p-values across these three tissues, we obtained 141 significant risk genes including 34 genes primarily due to trans-eQTL and 35 mapped risk genes in GWAS Catalog. With these 141 significant risk genes, we detected functional clusters comprised of both known mapped GWAS risk genes of AD in GWAS Catalog and our identified TWAS risk genes by protein-protein interaction network analysis, as well as several enriched phenotypes related to AD.

Conclusion
We applied BGW-TWAS and aggregated Cauchy test methods to integrate both cis- and trans- eQTL data of brain and blood tissues with GWAS summary data, identifying 141 TWAS risk genes of AD dementia. These identified risk genes provide novel insights into the underlying biological mechanisms of AD dementia and potential gene targets for therapeutics development.
TORSEL, a 4EBP1-based mTORC1 live-cell sensor, reveals nutrient-sensing targeting by histone deacetylase inhibitors
Authors: Li Canrong , Yi Yuguo , Ouyang Yingyi , Chen Fengzhi , Lu Chuxin , Peng Shujun , Wang Yifan , Chen Xinyu , Yan Xiao , Xu Haolun , Li Shuiming , Feng Lin , Xie Xiaoduo 
Published: June 2024

Abstract
Background
Mammalian or mechanistic target of rapamycin complex 1 (mTORC1) is an effective therapeutic target for diseases such as cancer, diabetes, aging, and neurodegeneration. However, an efficient tool for monitoring mTORC1 inhibition in living cells or tissues is lacking.

Results
We developed a genetically encoded mTORC1 sensor called TORSEL. This sensor changes its fluorescence pattern from diffuse to punctate when 4EBP1 dephosphorylation occurs and interacts with eIF4E. TORSEL can specifically sense the physiological, pharmacological, and genetic inhibition of mTORC1 signaling in living cells and tissues. Importantly, TORSEL is a valuable tool for imaging-based visual screening of mTORC1 inhibitors. Using TORSEL, we identified histone deacetylase inhibitors that selectively block nutrient-sensing signaling to inhibit mTORC1.

Conclusions
TORSEL is a unique living cell sensor that efficiently detects the inhibition of mTORC1 activity, and histone deacetylase inhibitors such as panobinostat target mTORC1 signaling through amino acid sensing.