bluuebunny/crossref_metadata_2025 huggingface dataset:
Umbilical cord blood derived cell expansion: a potential neuroprotective therapy
Authors: Penny Tayla R. , Jenkin Graham , Miller Suzanne L. , McDonald Courtney A.
Published: July 2024

Umbilical cord blood (UCB) is a rich source of beneficial stem and progenitor cells with known angiogenic, neuroregenerative and immune-modulatory properties. Preclinical studies have highlighted the benefit of UCB for a broad range of conditions including haematological conditions, metabolic disorders and neurological conditions, however clinical translation of UCB therapies is lacking. One barrier for clinical translation is inadequate cell numbers in some samples meaning that often a therapeutic dose cannot be achieved. This is particularly important when treating adults or when administering repeat doses of cells. To overcome this, UCB cell expansion is being explored to increase cell numbers. The current focus of UCB cell expansion is CD34+ haematopoietic stem cells (HSCs) for which the main application is treatment of haematological conditions. Currently there are 36 registered clinical trials that are examining the efficacy of expanded UCB cells with 31 of these being for haematological malignancies. Early data from these trials suggest that expanded UCB cells are a safe and feasible treatment option and show greater engraftment potential than unexpanded UCB. Outside of the haematology research space, expanded UCB has been trialled as a therapy in only two preclinical studies, one for spinal cord injury and one for hind limb ischemia. Proteomic analysis of expanded UCB cells in these studies showed that the cells were neuroprotective, anti-inflammatory and angiogenic. These findings are also supported by in vitro studies where expanded UCB CD34+ cells showed increased gene expression of neurotrophic and angiogenic factors compared to unexpanded CD34+ cells. Preclinical evidence demonstrates that unexpanded CD34+ cells are a promising therapy for neurological conditions where they have been shown to improve multiple indices of injury in rodent models of stroke, Parkinson’s disease and neonatal hypoxic ischemic brain injury. This review will highlight the current application of expanded UCB derived HSCs in transplant medicine, and also explore the potential use of expanded HSCs as a therapy for neurological conditions. It is proposed that expanded UCB derived CD34+ cells are an appropriate cellular therapy for a range of neurological conditions in children and adults.
miR-340-3p-modified bone marrow mesenchymal stem cell-derived exosomes inhibit ferroptosis through METTL3-mediated m6A modification of HMOX1 to promote recovery of injured rat uterus
Authors: Xiao Bang , Zhu Yiqing , Liu Meng , Chen Meiting , Huang Chao , Xu Dabing , Wang Fang , Sun Shuhan , Huang Jinfeng , Sun Ningxia , Yang Fu
Published: July 2024

Background

Ferroptosis is associated with the pathological progression of hemorrhagic injury and ischemia–reperfusion injury. According to our previous study, exosomes formed through bone marrow mesenchymal stem cells modified with miR-340-3p (MB-exos) can restore damaged endometrium. However, the involvement of ferroptosis in endometrial injury and the effect of MB-exos on ferroptosis remain elusive.

Methods

The endometrial injury rat model was developed. Exosomes were obtained from the supernatants of bone marrow mesenchymal stromal cells (BMSCs) and miR-340/BMSCs through differential centrifugation. We conducted RNA-seq analysis on endometrial tissues obtained from the PBS and MB-exos groups. Ferroptosis was induced in endometrial stromal cells (ESCs) by treating them with erastin or RSL3, followed by treatment with B-exos or MB-exos. We assessed the endometrial total m6A modification level after injury and subsequent treatment with B-exos or MB-exos by methylation quantification assay. We performed meRIP-qPCR to analyze m6A modification-regulated endogenous mRNAs.

Results

We reveal that MB-exos facilitate the injured endometrium to recover by suppressing ferroptosis in endometrial stromal cells. The injured endometrium showed significantly upregulated N6-methyladenosine (m6A) modification levels; these levels were attenuated by MB-exos through downregulation of the methylase METTL3. Intriguingly, METTL3 downregulation appears to repress ferroptosis by stabilizing HMOX1 mRNA, thereby potentially elucidating the mechanism through which MB-exos inhibit ferroptosis in ESCs. We identified YTHDF2 as a critical m6A reader protein that contributes to HMOX1 mRNA degradation. YTHDF2 facilitates HMOX1 mRNA degradation by identifying the m6A binding site in the 3′-untranslated regions of HMOX1. In a rat model, treatment with MB-exos ameliorated endometrial injury-induced fibrosis by inhibiting ferroptosis in ESCs. Moreover, METTL3 short hairpin RNA-mediated inhibition of m6A modification enhanced the inhibitory effect of MB-exos on ferroptosis in endometrial injury.

Conclusions

Thus, these observations provide new insights regarding the molecular mechanisms responsible for endometrial recovery promotion by MB-exos and highlight m6A modification-dependent ferroptosis inhibition as a prospective therapeutic target to attenuate endometrial injury.
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

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

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

Every 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 contribution

This 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

Infection 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

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

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

Digital 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

Wild-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

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

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

Cancer-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.
FHS-adapter: fine-grained hierarchical semantic adapter for Chinese landscape paintings generation
Authors: Peng Xianlin , Hu Qiyao , Fan Fangqing , Xie Penglin , Zhang Yihan , Cao Rui
Published: July 2024

How to migrate text-to-image models based on pre-trained diffusion models to adapt them to domain generation tasks is a common problem. In particular, the generation task for Chinese landscape paintings with unique characteristics suffers from a scarcity of fine-grained contextual details specific to such artwork. Moreover, the use of substantial amounts of non-landscape painting data during pre-training predisposes the model to be swayed by alternative visual styles, thereby leading to generated images that inadvertently lack the distinctive traits inherent to Chinese paintings. In this paper, we propose a Fine-grained Hierarchical Semantic Adapter for Chinese landscape paintings generation, namely FHS-adapter. The method orchestrates the diffusion process in a batch-wise manner, leveraging external fine-grained multi-perspective information to guide it. It gradually diminishes the influence of other style images embedded in the pre-trained diffusion model, ultimately preserving a greater number of landscape painting elements. The encoder was also replaced with the Taiyi-CLIP encoder, which is adapted for Chinese. We propose T2ICLP, a multimodal dataset containing 10,000 high-quality image-text pairs of Chinese landscape paintings. Unlike previous datasets, this dataset extracts fine-grained textual information from four perspectives, including Meta, Description, Sentiment, Poem. We compared the proposed model with the mainstream diffusion-based T2I models. Through an anonymous user study, our FHS-adapter method performs well in simulating various aspects such as brushwork, e.g.‘Gou, Cun, Dian, Ran’ means hooking, texturing, dotting, and dyeing, compositional space, elemental proportions, and color usage of different painting genres and artists. Our dataset is available at https://github.com/T2ICLP/t2iclp.
Recombinant GH3 β-glucosidase stimulated by xylose and tolerant to furfural and 5-hydroxymethylfurfural obtained from Aspergillus nidulans
Authors: de Andrades Diandra , Alnoch Robson C. , Alves Gabriela S. , Salgado Jose C. S. , Almeida Paula Z. , Berto Gabriela Leila , Segato Fernando , Ward Richard J. , Buckeridge Marcos S. , Polizeli Maria de Lourdes T. M.
Published: July 2024

The β-glucosidase gene from Aspergillus nidulans FGSC A4 was cloned and overexpressed in the A. nidulans A773. The resulting purified β-glucosidase, named AnGH3, is a monomeric enzyme with a molecular weight of approximately 80 kDa, as confirmed by SDS-PAGE. Circular dichroism further validated its unique canonical barrel fold (β/α), a feature also observed in the 3D homology model of AnGH3. The most striking aspect of this recombinant enzyme is its robustness, as it retained 100% activity after 24 h of incubation at 45 and 50 ºC and pH 6.0. Even at 55 °C, it maintained 72% of its enzymatic activity after 6 h of incubation at the same pH. The kinetic parameters Vmax, KM, and Kcat/KM for ρ-nitrophenyl-β-D-glucopyranoside (ρNPG) and cellobiose were also determined. Using ρNPG, the enzyme demonstrated a Vmax of 212 U mg − 1, KM of 0.0607 mmol L − 1, and Kcat/KM of 4521 mmol L − 1 s − 1 when incubated at pH 6.0 and 65 °C. The KM, Vmax, and Kcat/KM using cellobiose were 2.7 mmol L − 1, 57 U mg − 1, and 27 mmol –1 s − 1, respectively. AnGH3 activity was significantly enhanced by xylose and ethanol at concentrations up to 1.5 mol L − 1 and 25%, respectively. Even in challenging conditions, at 65 °C and pH 6.0, the enzyme maintained its activity, retaining 100% and 70% of its initial activity in the presence of 200 mmol L − 1 furfural and 5-hydroxymethylfurfural (HMF), respectively. The potential of this enzyme was further demonstrated by its application in the saccharification of the forage grass Panicum maximum, where it led to a 48% increase in glucose release after 24 h. These unique characteristics, including high catalytic performance, good thermal stability in hydrolysis temperature, and tolerance to elevated concentrations of ethanol, D-xylose, furfural, and HMF, position this recombinant enzyme as a promising tool in the hydrolysis of lignocellulosic biomass as part of an efficient multi-enzyme cocktail, thereby opening new avenues in the field of biotechnology and enzymology.
Concentration modulated microstructure and rheological properties of nanofibrous hydrogels derived from decellularized human amniotic membrane for 3D cell culture
Authors: Kafili Golara , Tamjid Elnaz , Niknejad Hassan , Simchi Abdolreza
Published: July 2024

Decellularized amnion (dAM)-derived hydrogels have been extensively exploited for versatile medical and therapeutical applications, particularly for soft tissue engineering of skin, vascular graft, and endometrium. In contrast to polyacrylamide-based hydrogels, which have been extensively employed as a 3D cell culture platform, the cell response of dAM hydrogel is yet to be understood. In this study, we have prepared hydrogels containing different concentrations of dAM and systematically investigated their microstructural features, gelation kinetics, and rheological properties. The results show that dAM hydrogels possess a network of fibers with an average diameter of 56 ± 5 nm at 1% dAM, which increases to 110 ± 14 nm at 3% dAM. The enhanced intermolecular crosslinking between the microfibrillar units increases the gelation rate in the growth phase of the self-assembly process. Moreover, increasing the concentration of dAM in the hydrogel formulation (from 1 to 3%w/v) enhances the dynamic mechanical moduli of the derived hydrogels by about two orders of magnitude (from 41.8 ± 2.5 to 896.2 ± 72.3 Pa). It is shown that the variation in the hydrogel stiffness significantly affects the morphology of dermal fibroblast cells cultured in the hydrogels. It is shown that the hydrogels containing up to 2%w/v dAM provide a suitable microenvironment for embedded fibroblast cells with spindle-like morphology. Nevertheless, at the higher concentration, an adverse effect on the proliferation and morphology of fibroblast cells is noticed due to stiffness-induced phenotype transformation of cells. Concentration-modulated properties of dAM hydrogels offer an in vitro platform to study cell-related responses, disease modeling, and drug studies.

Graphical abstract
Feasibility and acceptability of an online multicomponent very low-carbohydrate intervention in young adult women with obesity: a pilot study
Authors: Saslow Laura R. , O’Brien Alison , Raymond Kaitlyn , Bayandorian Hovig , Marriott Deanna , Moskowitz Judith T. , Daubenmier Jennifer , Bridges Dave , Cousineau Cody M. , Griauzde Dina H.
Published: July 2024

Background

Approximately one-third of US young adults (18–25 years) have obesity, and there are calls to help young adults lose weight to prevent weight-related chronic conditions. This pilot trial tested the feasibility and acceptability of a very low-carbohydrate (VLC) eating pattern, with supportive positive affect and mindful eating skills, for weight management among young females with obesity.

Methods

In a single-arm trial, women (N = 17), aged 19–23, with obesity participated in a 4-month diet and lifestyle intervention. Participants were taught how to follow a VLC eating pattern with the help of a coach and 16 weekly web-based sessions. We assessed feasibility and acceptability through session participation, outcome collection, intervention satisfaction, and adverse events.

Results

Seventeen participants enrolled and 14 (82%) reported body weight at 4 months. Fifteen participants (94% of those beginning the intervention) viewed at least one session, and 8/15 (53%) of these participants were active in the intervention, viewing at least half of the sessions. Among the nine participants who provided 4-month self-report information, intervention satisfaction was high (mean 5.89/7, 95% CI 4.59 to 7.19). Among participants with a 4-month body weight, 7/14 (50%) lost ≥ 5% of their body weight, and of those who were also active in the intervention, 6/7 (86%) lost ≥ 5% of their body weight. There were no serious adverse events.

Conclusions

The results of this pilot study suggest that a VLC eating pattern may be a feasible and acceptable approach for weight loss in some young women with obesity.

Trial registration

This trial was registered with ClinicalTrials.gov on August 18, 2021. The trial number is NCT05010083.
Google search volume index and investor attention in stock market: a systematic review
Authors: Ayala María José , Gonzálvez-Gallego Nicolás , Arteaga-Sánchez Rocío
Published: July 2024

This study systematically reviewed the literature on using the Google Search Volume Index (GSVI) as a proxy variable for investor attention and stock market movements. We analyzed 56 academic studies published between 2010 and 2021 using the Web of Sciences and ScienceDirect databases. The articles were classified and synthesized based on the selection criteria for building the GSVI: keywords of the search term, market region, and frequency of the data sample. Next, we analyze the effect of returns, volatility, and trading volume on the financial variables. The main results can be summarized as follows. (1) The GSVI is positively related to volatility and trading volume regardless of the keyword, market region, or frequency used for the sample. Hence, increasing investor attention toward a specific financial term will increase volatility and trading volume. (2) The GSVI can improve forecasting models for stock market movements. To conclude, this study consolidates, for the first time, the research literature on GSVI, which is highly valuable for academic practitioners in the area.
Co-creating and hosting PxP: a conference about patient engagement in research for and by patient partners
Authors: Richards Dawn P. , Mulhall Hetty , Belton Joletta , de Souza Savia , Flynn Trudy , Haagaard Alex , Hunter Linda , Price Amy , Riggare Sara , Tufte Janice , Twomey Rosie , Khan Karim M.
Published: July 2024

Research projects, initiatives and conferences that include patients as partners rather than as participants are becoming more common. Including patients as partners (what we will call ‘patient partners’) is an approach called patient engagement or involvement in research, and we will call it patient engagement throughout this paper. Patient engagement moves traditional health research conferences and events to include a broader audience for their knowledge exchange and community building efforts, beyond academics and healthcare professionals. However, there are few examples of conferences where patients are given the opportunity to fully lead. Our conference went beyond patient engagement – it was patient-led. Patient partners conceived, planned, and decided on all aspects of a virtual conference.

We present the work and processes we undertook throughout 2023 to create and produce a free conference called “PxP: For patients, by patients” or PxP for short, with a tagline of “Partnering to make research stronger.” PxP was patient-led and about patient engagement in research rather than a specific disease or condition. PxP was supported by the Canadian Institutes of Health Research Institute of Musculoskeletal Health and Arthritis. The PxP website, known as the PxP Hub, now houses the conference recordings along with resources about patient engagement in research. These resources were recommended by the PxP Steering Committee members, speakers, and others who attended the 2023 conference. Here we lead you through how the idea for PxP was generated; how the international patient partner Steering Committee was convened and supported; how PxP was brought to life over nine months; the PxP 3-day event and feedback collected to improve future efforts; trade-offs, challenges and learnings; and resources required to support this type of event. We close with what the future holds for PxP in 2024 and beyond.

It’s time to elevate patients into leadership roles for conferences and events, and we encourage you to adopt the PxP ethos by using or adapting our approach and resources to support your opportunity.
Long-term functional, anatomical outcome, and qualitative analysis by OCTA, as a predictor of disease recurrences in patients with choroidal neovascularization secondary to angioid streaks
Authors: Velez-Montoya Raul , Osorio-Landa Hillary K. , Franco-Ramirez K. Carolina , Martínez-Pacheco Victor , Ramirez-Estudillo J. Abel , Rosales-Padrón Jaime Francisco , Ledesma-Gil Gerardo , Fromow-Guerra Jans
Published: July 2024

Background

To report the risk of exudation recurrence and long-term outcomes in patients with choroidal neovascularization secondary to angioid streaks, according to its morphology and characteristics by optical coherence tomography angiography.

Methods

Retrospective analysis of electronic medical records from three hospitals. We enrolled patients with a clinical diagnosis of angioid streaks choroidal neovascularization that had a minimum follow-up of 12 months. From each record, we extracted general demographic data, best corrected visual acuity (baseline, before and after each disease recurrence and last on file), type of treatment, time between last intravitreal injection and disease recurrence, and classification of the neovascular lesion morphology by optical coherence tomography, and optical coherence tomography angiography. Patients with myopic choroidal neovascularization were used as controls. Interobserver agreement was assessed with a Cohen-Kappa test. The Odds ratio was calculated with a chi2 test for significance. Visual acuity change through time was evaluated with an ANOVA for repeated measurements with an alpha value of 0.05 for statistical significance.

Results

We enrolled 30 patients in the study group and 14 in the control group. In the study group, the baseline and final BCVA were 0.861 ± 0.59 and 1.095 ± 0.61 logMAR (p = 0.1) respectively. Control group: 1.045 ± 0.57 and 0.617 ± 0.53 logMAR (p < 0.05). In the study group, the predominant CNV type by OCTA was mixed (37%), and interlacing (57%) in the control group. Mixed and cog-wheel patterns at baseline had increased Odds for recurrence in the study group (p = 0.09). Patients in the study group required more intravitreal injections on each recurrence episode to achieve disease control (3.5 ± 1.5 vs.1.4 ± 0.2, p < 0.01).

Conclusions

The benefits of anti-VEGF treatment are lost over time in patients with angioid streaks and CNV. Lesion characteristics by optical coherence tomography angiography could help physicians predict the risk of recurrence.

Trial registration

Retrospective registered, and IRB approved.
Prevalence of Strongyloides stercoralis and other helminths in four districts of Madagascar
Authors: Scarso Salvatore , Rakotoarivelo Rivo Andry , Hey Jana Christina , Rasamoelina Tahinamandranto , Razafindrakoto Anjarasoa Ravo , Rasolojaona Zaraniaina Tahiry , Razafindralava Nantenaina Mathieu , Remkes Aaron , Rakotozandrindrainy Njary , Rasoamanamihaja Clara Fabienne , Schwarz Norbert Georg , May Jürgen , Rakotozandrindrainy Raphael , Marchese Valentina , Formenti Fabio , Perandin Francesca , Tamarozzi Francesca , Mazzi Cristina , Fusco Daniela , Buonfrate Dora
Published: July 2024

Background

Estimation of prevalence of Strongyloides stercoralis infection is required in endemic areas, in order to identify areas in need of control programmes. Data on prevalence of strongyloidiasis in Madagascar are scant. Aim of this work was to estimate prevalence of S. stercoralis in four districts of Madagascar.

Methods

Fecal and serum samples collected in the context of a previous study on schistosomiasis were tested with S. stercoralis real-time PCR and serology, respectively. A multiplex real-time PCR for Ascaris lumbricoides, Ancylostoma duodenalis, Necator americanus, and Trichuris trichiura was done on fecal samples collected in the areas demonstrating higher prevalence of strongyloidiasis. Comparisons between proportions were made using Fisher exact test, with false discovery rate correction used for post-hoc comparisons. A multivariable Firth logistic regression model was used to assess potential risk factors for S. stercoralis infection.

Results

Overall, 1775 serum samples were tested, of which 102 of 487 (20.9%) and 104 of 296 (35.2%) were serological-positive in Marovoay and in Vatomandry districts (both coastal areas), respectively, compared to 28 of 496 (5.6%) and 30 of 496 (6.1%) in Tsiroanomandidy and in Ambositra districts (both highlands), respectively (adj. p < 0.001). PCR for S. stercoralis was positive in 15 of 210 (7.1%) and in 11 of 296 (3.7%) samples from Marovoay from Vatomandry, respectively, while was negative for all samples tested in the other two districts. High prevalence of A. lumbricoides (45.9%), hookworm (44.6%) and T. trichiura (32.1%) was found in Vatomandry. In the multivariable analysis, strongyloidiasis was associated with hookworm infection. Hookworm infection was also associated with male sex and lower education level.

Conclusions

S. stercoralis prevalence proved higher in coastal areas compared to highlands. Different climatic conditions may explain this distribution, along with previous rounds of anthelminthics distributed in the country, which may have reduced the parasite load in the population. The high prevalence of the other soil-transmitted helminths (STH) in Vatomandry was unexpected, given the good coverage with benzimidazole in control campaigns. Further studies are needed to explore the risk factors for STH and S. stercoralis infections in Madagascar, in order to align with the WHO recommendations.
Ketamine in fibromyalgia: a systematic review
Authors: de Carvalho Jozélio Freire , de Sena Eduardo Pondé
Published: July 2024

Objective

Fibromyalgia (FM) subjects are treated with antidepressant agents; in most cases, these drugs lose efficacy or have adverse effects. Ketamine is an anesthetic drug used in FM in some studies. This article aims to systematically review the safety and efficacy of ketamine in fibromyalgia (FM) patients.

Materials and methods

We systematically searched articles on FM and ketamine published at Pubmed from 1966 to 2021. This study was registered at PROSPERO.

Results

There were only 6 articles published in this field, with a total of 115 patients. The female sex was predominant (88 to 100%). The age varied from 23 to 53 years old. Disease duration ranged from 1 month to 28 years. The dosage of ketamine changed from 0.1 mg/kg-0.3-0.5 mg/kg in intravenous infusion (4/5) and subcutaneous application (1/5). Regarding outcomes, the Visual analog scale (VAS) before ketamine was from 59 to 100 mm and after treatment from 2 to 95 mm. Most short-term studies had a good response. Only the study with 8 weeks of follow-up did not observe a good response. Side effects were common; all appeared during the infusion and disappeared after a few minutes of the ketamine injection.

Conclusions

The present study demonstrates the effectiveness and safety of ketamine in FM patients in the short term. Although, more studies, including long-term follow-up studies, are still needed.