bluuebunny/crossref_metadata_2025_split huggingface dataset:
Secretome from iPSC-derived MSCs exerts proangiogenic and immunosuppressive effects to alleviate radiation-induced vascular endothelial cell damage
Authors: Gupta Kshama , Perkerson Ralph B. , Parsons Tammee M. , Angom Ramacharan , Amerna Danilyn , Burgess Jeremy D. , Ren Yingxue , McLean Pamela J. , Mukhopadhyay Debabrata , Vibhute Prasanna , Wszolek Zbigniew K. , Zubair Abba C. , Quiñones-Hinojosa Alfredo , Kanekiyo Takahisa 
Published: July 2024

Abstract
Background
Radiation therapy is the standard of care for central nervous system tumours. Despite the success of radiation therapy in reducing tumour mass, irradiation (IR)-induced vasculopathies and neuroinflammation contribute to late-delayed complications, neurodegeneration, and premature ageing in long-term cancer survivors. Mesenchymal stromal cells (MSCs) are adult stem cells that facilitate tissue integrity, homeostasis, and repair. Here, we investigated the potential of the iPSC-derived MSC (iMSC) secretome in immunomodulation and vasculature repair in response to radiation injury utilizing human cell lines.

Methods
We generated iPSC-derived iMSC lines and evaluated the potential of their conditioned media (iMSC CM) to treat IR-induced injuries in human monocytes (THP1) and brain vascular endothelial cells (hCMEC/D3). We further assessed factors in the iMSC secretome, their modulation, and the molecular pathways they elicit.

Results
Increasing doses of IR disturbed endothelial tube and spheroid formation in hCMEC/D3. When IR-injured hCMEC/D3 (IR ≤ 5 Gy) were treated with iMSC CM, endothelial cell viability, adherence, spheroid compactness, and proangiogenic sprout formation were significantly ameliorated, and IR-induced ROS levels were reduced. iMSC CM augmented tube formation in cocultures of hCMEC/D3 and iMSCs. Consistently, iMSC CM facilitated angiogenesis in a zebrafish model in vivo. Furthermore, iMSC CM suppressed IR-induced NFκB activation, TNF-α release, and ROS production in THP1 cells. Additionally, iMSC CM diminished NF-kB activation in THP1 cells cocultured with irradiated hCMEC/D3, iMSCs, or HMC3 microglial lines. The cytokine array revealed that iMSC CM contains the proangiogenic and immunosuppressive factors MCP1/CCL2, IL6, IL8/CXCL8, ANG (Angiogenin), GROα/CXCL1, and RANTES/CCL5. Common promoter regulatory elements were enriched in TF-binding motifs such as androgen receptor (ANDR) and GATA2. hCMEC/D3 phosphokinome profiling revealed increased expression of pro-survival factors, the PI3K/AKT/mTOR modulator PRAS40 and β-catenin in response to CM. The transcriptome analysis revealed increased expression of GATA2 in iMSCs and the enrichment of pathways involved in RNA metabolism, translation, mitochondrial respiration, DNA damage repair, and neurodevelopment.

Conclusions
The iMSC secretome is a comodulated composite of proangiogenic and immunosuppressive factors that has the potential to alleviate radiation-induced vascular endothelial cell damage and immune activation.
Deciphering decidual deficiencies in recurrent spontaneous abortion and the therapeutic potential of mesenchymal stem cells at single-cell resolution
Authors: Jin Beibei , Ding Xiaoying , Dai Jiamin , Peng Chen , Zhu Chunyu , Wei Qinru , Chen Xinyi , Qiang Ronghui , Ding Xiaoyi , Du Hongxiang , Deng Wenbo , Yang Xiaoqing 
Published: July 2024

Abstract
Background
Recurrent spontaneous abortion (RSA) is a challenging condition that affects the health of women both physically and mentally, but its pathogenesis and treatment have yet to be studied in detail. In recent years, Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) have been shown to be effective in treating various diseases. Current understanding of RSA treatment using WJ-MSCs is limited, and the exact mechanisms of WJ-MSCs action in RSA remains largely unclear. In this study, we explored the decidual deficiencies in RSA and the therapeutic potential of WJ-MSCs at single-cell resolution.

Methods
Three mouse models were established: a normal pregnancy group, an RSA group, and a WJ-MSC treatment group. Decidual tissue samples were collected for single-cell RNA sequencing (scRNA-seq) and functional verification, including single-cell resolution in situ hybridization on tissues (SCRINSHOT) and immunofluorescence.

Results
We generated a single-cell atlas of decidual tissues from normal pregnant, RSA, and WJ-MSC-treated mice and identified 14 cell clusters in the decidua on day 14. Among these cell populations, stromal cells were the most abundant cell clusters in the decidua, and we further identified three novel subclusters (Str_0, Str_1, and Str_2). We also demonstrated that the IL17 and TNF signaling pathways were enriched for upregulated DEGs of stromal cells in RSA mice. Intriguingly, cell–cell communication analysis revealed that Str_1 cell-related gene expression was greatly reduced in the RSA group and rescued in the WJ-MSC treatment group. Notably, the interaction between NK cells and other cells in the RSA group was attenuated, and the expression of Spp1 (identified as an endometrial toleration-related marker) was significantly reduced in the NK cells of the RSA group but could be restored by WJ-MSC treatment.

Conclusion
Herein, we implemented scRNA-seq to systematically evaluate the cellular heterogeneity and transcriptional regulatory networks associated with RSA and its treatment with WJ-MSCs. These data revealed potential therapeutic targets of WJ-MSCs to remodel the decidual subpopulations in RSA and provided new insights into decidua-derived developmental defects at the maternal–foetal interface.
A computational workflow for analysis of missense mutations in precision oncology
Authors: Khan Rayyan Tariq , Pokorna Petra , Stourac Jan , Borko Simeon , Arefiev Ihor , Planas-Iglesias Joan , Dobias Adam , Pinto Gaspar , Szotkowska Veronika , Sterba Jaroslav , Slaby Ondrej , Damborsky Jiri , Mazurenko Stanislav , Bednar David 
Published: July 2024

AbstractEvery year, more than 19 million cancer cases are diagnosed, and this number continues to increase annually. Since standard treatment options have varying success rates for different types of cancer, understanding the biology of an individual's tumour becomes crucial, especially for cases that are difficult to treat. Personalised high-throughput profiling, using next-generation sequencing, allows for a comprehensive examination of biopsy specimens. Furthermore, the widespread use of this technology has generated a wealth of information on cancer-specific gene alterations. However, there exists a significant gap between identified alterations and their proven impact on protein function. Here, we present a bioinformatics pipeline that enables fast analysis of a missense mutation’s effect on stability and function in known oncogenic proteins. This pipeline is coupled with a predictor that summarises the outputs of different tools used throughout the pipeline, providing a single probability score, achieving a balanced accuracy above 86%. The pipeline incorporates a virtual screening method to suggest potential FDA/EMA-approved drugs to be considered for treatment. We showcase three case studies to demonstrate the timely utility of this pipeline. To facilitate access and analysis of cancer-related mutations, we have packaged the pipeline as a web server, which is freely available at https://loschmidt.chemi.muni.cz/predictonco/.Scientific contributionThis work presents a novel bioinformatics pipeline that integrates multiple computational tools to predict the effects of missense mutations on proteins of oncological interest. The pipeline uniquely combines fast protein modelling, stability prediction, and evolutionary analysis with virtual drug screening, while offering actionable insights for precision oncology. This comprehensive approach surpasses existing tools by automating the interpretation of mutations and suggesting potential treatments, thereby striving to bridge the gap between sequencing data and clinical application.
Baicalin attenuates PD-1/PD-L1 axis-induced immunosuppression in piglets challenged with Glaesserella parasuis by inhibiting the PI3K/Akt/mTOR and RAS/MEK/ERK signalling pathways
Authors: Fu Shulin , Li Jingyang , You Jiarui , Liu Siyu , Dong Qiaoli , Fu Yunjian , Luo Ronghui , Sun Yamin , Tian Xinyue , Liu Wei , Zhang Jingyi , Ding Yu , Zhang Yitian , Wang Wutao , Guo Ling , Qiu Yinsheng 
Published: July 2024

AbstractInfection of piglets with Glaesserella parasuis (G. parasuis) induces host immunosuppression. However, the mechanism underlying the immunosuppression of piglets remains unclear. Activation of the PD-1/PD-L1 axis has been shown to trigger host immunosuppression. Baicalin possesses anti-inflammatory and immunomodulatory functions. However, whether baicalin inhibits PD-1/PD-L1 activation and thus alleviates host immunosuppression has not been investigated. In this study, the effect of baicalin on the attenuation of piglet immunosuppression induced by G. parasuis was evaluated. Seventy piglets were randomly divided into the control group, infection group, levamisole group, BMS-1 group, 25 mg/kg baicalin group, 50 mg/kg baicalin group and 100 mg/kg baicalin group. Following pretreatment with levamisole, BMS-1 or baicalin, the piglets were challenged with 1 × 108 CFU of G. parasuis. Our results showed that baicalin, levamisole and BMS-1 modified routine blood indicators and biochemical parameters; downregulated IL-1β, IL-10, IL-18, TNF-α and IFN-γ mRNA expression; and upregulated IL-2 and IL-8 mRNA expression in blood. Baicalin, levamisole and BMS-1 increased the proportions of CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+ T cells and CD3–CD21+ B cells in the splenocyte population, increased the proportions of CD3+ T cells, CD3+CD4+ T cells and CD3+CD8+ T cells in the blood, and inhibited PD-1/PD-L1 and TIM-3 activation. Baicalin, levamisole and BMS-1 reduced p-PI3K, p-Akt, and p-mTOR expression, the p-MEK1/2/MEK1/2 and p-ERK1/2/ERK1/2 ratios and increased RAS expression. Baicalin, levamisole and BMS-1 provided substantial protection against G. parasuis challenge and relieved tissue histopathological damage. Our findings might provide new strategies for controlling G. parasuis infection and other immunosuppressive diseases.
Long term cognitive dysfunction among critical care survivors: associated factors and quality of life—a multicenter cohort study
Authors: Jesus Pereira Isabel , Santos Mariana , Sganzerla Daniel , Robinson Caroline Cabral , de Souza Denise , Kochhann Renata , Falavigna Maicon , Azevedo Luis , Bozza Fernando , Sharshar Tarek , Goulart Rosa Regis , Granja Cristina , Teixeira Cassiano 
Published: July 2024

Abstract
Objectives
To identify the prevalence and associated factors of cognitive dysfunction, 1 year after ICU discharge, among adult patients, and it´s relation with quality of life.

Methods
Multicenter, prospective cohort study including ICUs of 10 tertiary hospitals in Brazil, between May 2014 and December 2018. The patients included were 452 adult ICU survivors (median age 60; 47.6% women) with an ICU stay greater than 72 h.

Results
At 12 months after ICU discharge, a Montreal Cognitive Assessment (tMOCA) telephone score of less than 12 was defined as cognitive dysfunction. At 12 months, of the 452 ICU survivors who completed the cognitive evaluation 216 (47.8%) had cognitive dysfunction.
In multivariable analyses, the factors associated with long-term (1-year) cognitive dysfunction were older age (Prevalence Ratio–PR = 1.44, P < 0.001), absence of higher education (PR = 2.81, P = 0.005), higher comorbidities on admission (PR = 1.089; P = 0.004) and delirium (PR = 1.13, P < 0.001). Health-related Quality of life (HRQoL), assessed by the mental and physical dimensions of the SF-12v2, was significantly better in patients without cognitive dysfunction (Mental SF-12v2 Mean difference = 2.54; CI 95%, − 4.80/− 0.28; p = 0.028 and Physical SF-12v2 Mean difference = − 2.85; CI 95%, − 5.20/− 0.50; P = 0.018).

Conclusions
Delirium was found to be the main modifiable predictor of long-term cognitive dysfunction in ICU survivors. Higher education consistently reduced the probability of having long-term cognitive dysfunction. Cognitive dysfunction significantly influenced patients’ quality of life, leading us to emphasize the importance of cognitive reserve for long-term prognosis after ICU discharge.
Bloodstream infections among patients receiving therapeutic plasma exchanges in the intensive care unit: a 10 year multicentric study
Authors: Fodil Sofiane , Urbina Tomas , Bredin Swann , Mayaux Julien , Lafarge Antoine , Missri Louaï , Maury Eric , Demoule Alexandre , Pene Frederic , Mariotte Eric , Ait-Oufella Hafid 
Published: July 2024

Abstract
Background
Therapeutic plasma exchanges (TPE), which affect the humoral response, are often performed in combination with immunosuppressive drugs. For this reason, TPE may be associated with an increased susceptibility to infections. We aimed to describe blood stream infection (BSI) incidence in ICU patients treated with TPE and to identify associated risk factors.

Methods
We retrospectively included patients that had received at least one session of TPE in the ICU of one of the 4 participating centers (all in Paris, France) between January 1st 2010 and December 31th 2019. Patients presenting with a BSI during ICU stay were compared to patients without such an infection. Risk factors for BSI were identified by a multivariate logistic regression model.

Results
Over 10 years in the 4 ICUs, 387 patients were included, with a median of 5 [2–7] TPE sessions per patient. Most frequent indications for TPE were thrombotic microangiopathy (47%), central nervous system inflammatory disorders (11%), hyperviscosity syndrome (11%) and ANCA associated vasculitis (8.5%). Thirty-one patients (8%) presented with a BSI during their ICU stay, a median of 7 [3–11] days after start of TPE. In a multivariate logistic regression model, diabetes (OR 3.32 [1.21–8.32]) and total number of TPE sessions (OR 1.14 [1.08–1.20]) were independent risk factors for BSI. There was no difference between TPE catheter infection related BSI (n = 11 (35%)) and other sources of BSI (n = 20 (65%)) regarding catheter insertion site (p = 0.458) or rate of TPE catheter related deep vein thrombosis (p = 0.601). ICU course was severe in patients presenting with BSI when compared to patients without BSI, with higher need for mechanical ventilation (45% vs 18%, p = 0.001), renal replacement therapy (42% vs 20%, p = 0.011), vasopressors (32% vs 12%, p = 0.004) and a higher mortality (19% vs 5%, p = 0.010).

Conclusion
Blood stream infections are frequent in patients receiving TPE in the ICU, and are associated with a severe ICU course. Vigilant monitoring is crucial particularly for patients receiving a high number of TPE sessions.
Digital transformation in incumbent companies: a qualitative study on exploration and exploitation activities in innovation
Authors: Hoessler Sabrina , Carbon Claus-Christian 
Published: July 2024

AbstractDigital transformation is a pivotal strategic pillar for companies. Despite its relevance, incumbent companies still face challenges in implementation due to the complex character of transformation processes. We provide a framework serving as guidance for leaders of digital transformations. Based on an explorative research design, we conducted 33 semi-structured interviews with experts of digital transformations of incumbent companies. Our findings indicate that leaders need to understand the terminologies related to exploration, exploitation, and digital transformation, and the complex interaction between all three areas. This includes digital literacy and being aware of differentiated treatment of exploration and exploitation in innovations and the relevance of both. Leaders must acknowledge that industry and organizational characteristics influence organizations’ tendencies towards exploration or exploitation in innovations. Exploration in digital transformation is about using digital technologies to rethink business models. Using digital technologies to optimize existing processes, products, and IT infrastructure is associated with exploitation. In sum, we need different target settings and approaches for the required activities.
Changes in growth characteristics and ginsenoside contents of wild-simulated ginseng with different harvest times in South Korea
Authors: Yun Yeong-Bae , Kwon Hae-Yun , Um Yurry 
Published: July 2024

AbstractWild-simulated ginseng (WSG, Panax ginseng C.A. Meyer) is grown in mountainous forests, without the chemical treatment or installation of artificial facilities. This study aimed to investigate monthly changes in growth characteristics and ginsenoside contents in WSG to suggest the optimal harvest time. Four-year-old WSG were collected in the same area every month, and their growth characteristics and ginsenoside contents were measured. The growth characteristics of aerial and root parts were measured from May to July and from March to December, respectively. For the aerial part, most growth characteristics of WSG decreased over time, except for stem length. For the root part, rhizome length increased over time except for September, while the root diameter and weight of root part were mostly consistent. The root length increased by September, while the number of rootlets was the highest at May. At July, the total ginsenoside content of WSG was significantly the highest, while the total ginsenoside content at October was the lowest. This result was believed to be due to the F2, Rd, and Rg1 contents of the aerial part, rather than the root part. Also, based on these growths and the ginsenoside contents of WSG, the optimal harvest time for WSG is considered to be late spring–summer (May–July) when the aerial part can be identified.
The obesity paradox and 90 day mortality in chronic critically ill patients: a cohort study using a large clinical database
Authors: Xu Danyu , Lu Yan , Wang Yan , Li Feng 
Published: July 2024

Abstract
Background
This study investigates the obesity paradox, where obesity is linked to lower mortality in certain patient groups, focusing on its impact on long-term mortality in chronic critically ill (CCI) patients.

Methods
We retrospectively analyzed CCI patients from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database’s Intensive Care Unit, categorizing them into six groups based on Body Mass Index (BMI). Using stepwise multivariable Cox regression and restricted cubic spline models, we examined the association between BMI and 90 day mortality, accounting for confounding variables through subgroup analyses.

Results
The study included 1996 CCI patients, revealing a 90 day mortality of 34.12%. Overweight and obese patients exhibited significantly lower mortality compared to normal-weight individuals. Adjusted analysis showed lower mortality risks in overweight and obese groups (HRs 0.60 to 0.72, p < 0.001). The cubic spline model indicated a negative correlation between BMI and 90 day mortality, with subgroup analyses highlighting interactions with age.

Conclusion
Our findings confirm the obesity paradox in CCI patients, especially among the elderly (65–85 years) and very elderly (≥ 85 years). The results suggest a beneficial association of higher BMI in older CCI patients, though caution is advised for those under 45.
Clinical outcomes of patients with mut-type methylmalonic acidemia identified through expanded newborn screening in China
Authors: Ling Shiying , Wu Shengnan , Shuai Ruixue , Yu Yue , Qiu Wenjuan , Wei Haiyan , Yang Chiju , Xu Peng , Zou Hui , Feng Jizhen , Niu Tingting , Hu Haili , Zhang Huiwen , Liang Lili , Wang Yu , Chen Ting , Xu Feng , Gu Xuefan , Han Lianshu 
Published: July 2024

Abstract
Background
Isolated methylmalonic acidemia, an autosomal recessive disorder of propionate metabolism, is usually caused by mutations in the methylmalonyl-CoA mutase gene (mut-type). Because no universal consensus was made on whether mut-type methylmalonic acidemia should be included in newborn screening (NBS), we aimed to compare the outcome of this disorder detected by NBS with that detected clinically and investigate the influence of NBS on the disease course.

Design & methods
In this study, 168 patients with mut-type methylmalonic acidemia diagnosed by NBS were compared to 210 patients diagnosed after disease onset while NBS was not performed. Clinical data of these patients from 7 metabolic centers in China were analyzed retrospectively, including initial manifestations, biochemical metabolites, the responsiveness of vitamin B12 therapy, and gene variation, to explore different factors on the long-term outcome.

Results
By comparison of the clinically-diagnosed patients, NBS-detected patients showed younger age at diagnosis, less incidence of disease onset, better responsiveness of vitamin B12, younger age at start of treatment, lower levels of biochemical features before and after treatment, and better long-term prognosis (P < 0.01). Onset of disease, blood C3/C2 ratio and unresponsiveness of vitamin B12 were more positively associated with poor outcomes of patients whether identified by NBS. Moreover, the factors above as well as older age at start of treatment were positively associated with mortality.

Conclusions
This research highly demonstrated NBS could prevent major disease-related events and allow an earlier treatment initiation. As a key prognostic factor, NBS is beneficial for improving the overall survival of infants with mut-type methylmalonic acidemia.
Advances in targeting cancer-associated fibroblasts through single-cell spatial transcriptomic sequencing
Authors: Lyu Pin , Gu Xiaoming , Wang Fuqi , Sun Haifeng , Zhou Quanbo , Yang Shuaixi , Yuan Weitang 
Published: July 2024

AbstractCancer-associated fibroblasts (CAFs) are the major components of the tumor microenvironment and are related to tumor proliferation, metastasis, relapse, and drug resistance. With the development of sequencing technologies, single-cell RNA sequencing has become a popular method for identifying CAFs in the tumor microenvironment. Whereas the drawbacks of CAFs, such as the lack of a spatial landscape, still exist, recent research has utilized spatial transcriptomics combined with single-cell RNA sequencing to address this issue. These multiomics analyses can resolve the single-cell resolution problem in spatial transcriptomics. In this review, we summarized the recent literature regarding the targeting of CAFs to address drug resistance, angiogenesis, metabolic reprogramming and metastasis in tumor tissue.