bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extracorporeal membrane oxygenation as a bridge to lung transplantation: 5-year outcomes and bridge to decision in a large, older cohort
Authors: Daar Jared A. , Toyoda Yoshiya , Shigemura Norihisa , Baskin Sean M. , Desai Parag , Gordon Matthew 
Published: September 2024

AbstractBackgroundExtracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation (BTT) has expanded considerably, though evidence-based selection criteria and long-term outcome data are lacking. The purpose of this study was to evaluate whether risk factors often used to exclude patients from ECMO BTT—specifically older age and not yet being listed for transplant—are validated by long-term outcomes.MethodsTo ensure minimum 5-year follow-up, a retrospective cohort study was performed of adult patients actively listed for lung transplantation at a high-volume center and bridged on ECMO between January 2012 and December 2017. Data was collected through January 1, 2023.ResultsAmong 50 patients bridged on ECMO, 25 survived to transplant. Median age at listing was 58 (interquartile range [IQR], 42–65) in the transplanted group and 65 (IQR, 56.5–69) in the deceased group (P = 0.051). One-year, 3-year, and 5-year survival were 88% (22/25), 60% (15/25), and 44% (11/25), respectively, with eight patients still living at the time of review. Median time spent at home during the year post-transplant was 340 days (IQR, 314–355). Older age at listing was a negative predictor of survival on ECMO to transplant (odds ratio 0.92 [95% confidence interval, 0.86–0.99],P = 0.01). Thirteen patients were placed on ECMO prior to being listed and three were listed the same day as ECMO cannulation, with 10/16 transplanted. No significant difference in post-transplant survival was found between patients placed on ECMO prior to listing (n = 10) and those already listed (n = 15) (P = 0.93, log-rank). Serial post-transplant spirometry up to 5 years and surveillance transbronchial biopsy demonstrated good allograft function and low rates of cellular rejection.ConclusionsIn one of the oldest cohorts of ECMO BTT patients described, favorable survival outcomes and allograft function were observed up to 5 years irrespective of whether patients were previously listed or bridged to decision. Despite inherent limitations to this retrospective, single-center study, the data presented support the feasibility of ECMO BTT in older and not previously listed advanced lung disease patients.
A cross-sectional study investigating malaria prevalence and associated predictors of infection among migrants to a newly established gold mining settlement in the Gambella Region of Ethiopia
Authors: Glendening Natasha , Haileselassie Werissaw , Lee Ming-Chieh , Taye Behailu , Alemu Yonas , Belachew Ayele , Deressa Wakgari , Yan Guiyun , Parker Daniel M. 
Published: September 2024

Abstract
Background
Malaria is a major disease burden in Ethiopia. Migration can influence malaria transmission dynamics, with individuals relocating from malaria-free highland regions to malarious lowlands potentially facing elevated risks of contracting malaria. Migrants may find it difficult to protect themselves against malaria and have limited access to diagnosis or treatment. Settlers in gold mining sites are one type of migrant and are often neglected in malaria research yet may have particularly high malaria risk. This study was a malaria prevalence survey among settlers in a new gold mining settlement in the highly malarious Gambella Region, Ethiopia.

Methods
n = 590 people were surveyed for demographic information and their knowledge and practices of malaria. Participants were tested for malaria using rapid diagnostic tests and microscopy. Using logistic regressions, the influence of demographic characteristics on malaria infections and bed net access were analysed. A sub-sample of participants was interviewed to comprehend settlement living conditions and healthcare accessibility.

Results
The overall prevalence of Plasmodium falciparum was 37.5% (CI 32.4–42.3%). Young children were most likely to have malaria, with individuals aged 15–24 having 67% lower odds (aOR: 0.33; CI 0.13–0.86) of infection compared to those aged 1–4 years old. Meanwhile, those age 25-plus had 75% decreased odds of malaria infection (aOR 0.25; CI 0.10–0.65). Individuals with bed nets had ~ 50% decreased odds of testing positive for falciparum malaria than those reporting having no bed net (aOR: 0.47; CI 0.22–0.97). Individuals who relocated from low elevation with high malaria test positivity rate areas were more prone to testing positive for malaria, as were those residing in densely populated households with multiple malaria cases. Conversely, individuals from higher elevations with low malaria test positivity rates, and those living in households with 5–10 occupants and < 2 malaria infections, were more likely to possess bed nets.

Conclusions
This gold mining settlement provides an example of an oft-neglected atypical community where malaria is a significant, but under-addressed, health problem. Within this community, future interventions focused on distributing bed nets, particularly to larger households and those with children, have great potential to alleviate the malaria burden. Efforts should also be made to provide affordable, and accessible, early diagnosis and treatment.
Are toe fringes important for lizard burying in highly mobile sand?
Authors: Zheng Peng , Liang Tao , Shi Lei 
Published: September 2024

AbstractToe fringes are a key innovation for sand dwelling lizards, and the relationship between toe fringe function and substrate properties is helpful in understanding the adaptation of lizards to sand dune environments. We tested the sand burial performance of Phrynocephalus mystaceus on different sand substrates with toe fringe manipulation, with the aim of assessing whether the function of the toe fringes shifts under different substrate properties, especially in highly mobile substrates. The sand burial performance of P. mystaceus was influenced by substrate properties in relation to the toe fringe states of the lizard. After removal of the bilateral toe fringes, the sand burial ability score of P. mystaceus was significantly higher on sand substrates below 100 mesh than on native sand substrates. As the angle of stability of the substrate properties decreased, the sand burial performance of the lizard was even better after the bilateral toe fringes were removed. The results of the LASSO model and the path analysis model showed that the stability angle provided the opposite effect on sand burial performance in different toe fringe states. These results further suggest that the sand burial function of toe fringes may not be suitable for highly mobile sand substrates. It remains to be tested further whether the function of toe fringes is more important for running on sand.
A novel application of laser speckle imaging technique for prediction of hypoxic stress of apples
Authors: Pieczywek Piotr Mariusz , Nosalewicz Artur , Zdunek Artur 
Published: September 2024

Abstract
Background
Fruit storage methods such as dynamic controlled atmosphere (DCA) technology enable adjusting the level of oxygen in the storage room, according to the physiological state of the product to slow down the ripening process. However, the successful application of DCA requires precise and reliable sensors of the oxidative stress of the fruit. In this study, respiration rate and chlorophyll fluorescence (CF) signals were evaluated after introducing a novel predictors of apples' hypoxic stress based on laser speckle imaging technique (LSI).

Results
Both chlorophyll fluorescence and LSI signals were equally good for stress detection in principle. However, in an application with automatic detection based on machine learning models, the LSI signal proved to be superior, due to its stability and measurement repeatability. Moreover, the shortcomings of the CF signal appear to be its inability to indicate oxygen stress in tissues with low chlorophyll content but this does not apply to LSI. A comparison of different LSI signal processing methods showed that method based on the dynamics of changes in image content was better indicators of stress than methods based on measurements of changes in pixel brightness (inertia moment or laser speckle contrast analysis). Data obtained using the near-infrared laser provided better prediction capabilities, compared to the laser with red light.

Conclusions
The study showed that the signal from the scattered laser light phenomenon is a good predictor for the oxidative stress of apples. Results showed that effective prediction using LSI was possible and did not require additional signals. The proposed method has great potential as an alternative indicator of fruit oxidative stress, which can be applied in modern storage systems with a dynamically controlled atmosphere.
UBASH3B-mediated MRPL12 Y60 dephosphorylation inhibits LUAD development by driving mitochondrial metabolism reprogramming
Authors: Ji Xingzhao , Zhang Tianyi , Sun Jian , Song Xiaojia , Ma Guoyuan , Xu Li , Cao Xueru , jing yongjian , Xue Fuyuan , Zhang Weiying , Sun Shengnan , Wan Qiang , Liu Yi 
Published: September 2024

Abstract
Background
Metabolic reprogramming plays a pivotal role in tumorigenesis and development of lung adenocarcinoma (LUAD). However, the precise mechanisms and potential targets for metabolic reprogramming in LUAD remain elusive. Our prior investigations revealed that the mitochondrial ribosomal protein MRPL12, identified as a novel mitochondrial transcriptional regulatory gene, exerts a critical influence on mitochondrial metabolism. Despite this, the role and regulatory mechanisms underlying MRPL12’s transcriptional activity in cancers remain unexplored.

Methods
Human LUAD tissues, Tp53fl/fl;KrasG12D-driven LUAD mouse models, LUAD patient-derived organoids (PDO), and LUAD cell lines were used to explored the expression and function of MRPL12. The posttranslational modification of MRPL12 was analyzed by mass spectrometry, and the oncogenic role of key phosphorylation sites of MRPL12 in LUAD development was verified in vivo and in vitro.

Results
MRPL12 was upregulated in human LUAD tissues, Tp53fl/fl;KrasG12D-driven LUAD tissues in mice, LUAD PDO, and LUAD cell lines, correlating with poor patient survival. Overexpression of MRPL12 significantly promoted LUAD tumorigenesis, metastasis, and PDO formation, while MRPL12 knockdown elicited the opposite phenotype. Additionally, MRPL12 deletion in a Tp53fl/fl;KrasG12D-driven mouse LUAD model conferred a notable survival advantage, delaying tumor onset and reducing malignant progression. Mechanistically, we discovered that MRPL12 promotes tumor progression by upregulating mitochondrial oxidative phosphorylation. Furthermore, we identified UBASH3B as a specific binder of MRPL12, dephosphorylating tyrosine 60 in MRPL12 (MRPL12 Y60) and inhibiting its oncogenic functions. The decrease in MRPL12 Y60 phosphorylation impeded the binding of MRPL12 to POLRMT, downregulating mitochondrial metabolism in LUAD cells. In-depth in vivo, in vitro, and organoid models validated the inhibitory effect of MRPL12 Y60 mutation on LUAD.

Conclusion
This study establishes MRPL12 as a novel oncogene in LUAD, contributing to LUAD pathogenesis by orchestrating mitochondrial metabolism reprogramming towards oxidative phosphorylation (OXPHOS). Furthermore, it confirms Y60 as a specific phosphorylation modification site regulating MRPL12’s oncogenic functions, offering insights for the development of LUAD-specific targeted drugs and clinical interventions.

Graphical Abstract
Inactivation of HIPK2 attenuates KRASG12D activity and prevents pancreatic tumorigenesis
Authors: Sozzi Silvia , Manni Isabella , Ercolani Cristiana , Diodoro Maria Grazia , Bartolazzi Armando , Spallotta Francesco , Piaggio Giulia , Monteonofrio Laura , Soddu Silvia , Rinaldo Cinzia , Valente Davide 
Published: September 2024

Abstract
Background
Pancreatic ductal adenocarcinoma (PDAC) features KRAS mutations in approximately 90% of human cases and excessive stromal response, termed desmoplastic reaction. Oncogenic KRAS drives pancreatic carcinogenesis by acting on both epithelial cells and tumor microenvironment (TME). We have previously shown that Homeodomain-Interacting Protein Kinase 2 (HIPK2) cooperates with KRAS in sustaining ERK1/2 phosphorylation in human colorectal cancers. Here, we investigated whether HIPK2 contributes to oncogenic KRAS-driven tumorigenesis in vivo, in the onset of pancreatic cancer.

Methods
We employed an extensively characterized model of KRASG12D-dependent preinvasive PDAC, the Pdx1-Cre;LSL-KRasG12D/+ (KC) mice. In these mice, HIPK2 was inhibited by genetic knockout in the pancreatic epithelial cells (KCH−/−) or by pharmacologic inactivation with the small molecule 5-IodoTubercidin (5-ITu). The development of preneoplastic acinar-to-ductal metaplasia (ADM), intraepithelial neoplasia (PanIN), and their associated desmoplastic reaction were analyzed.

Results
In Hipk2-KO mice (KCH−/−), ERK phosphorylation was lowered, the appearance of ADM was slowed down, and both the number and pathologic grade of PanIN were reduced compared to Hipk2-WT KC mice. The pancreatic lesion phenotype in KCH−/− mice was characterized by abundant collagen fibers and reduced number of αSMA+ and pSTAT3+ desmoplastic cells. These features were reminiscent of the recently described human “deserted” sub-TME, poor in cells, rich in matrix, and associated with tumor differentiation. In contrast, the desmoplastic reaction of KC mice resembled the “reactive” sub-TME, rich in stromal cells and associated with tumor progression. These observations were confirmed by the pharmacologic inhibition of HIPK2 in KC mice.

Conclusion
This study demonstrates that HIPK2 inhibition weakens oncogenic KRAS activity and pancreatic tumorigenesis providing a rationale for testing HIPK2 inhibitors to mitigate the incidence of PDAC development in high-risk individuals.

Graphical Abstract
LncOCMRL1 promotes oral squamous cell carcinoma growth and metastasis via the RRM2/EMT pathway
Authors: Lu Nan , Jiang Qiming , Xu Tianshu , Gao Qiyuan , Wang Yuepeng , Huang Zixian , Huang Zhiquan , Xu Xiaoding 
Published: September 2024

Abstract
Background
Long noncoding RNAs (lncRNAs) are widely involved in cancer development and progression, but the functions of most lncRNAs have not yet been elucidated. Metastasis is the main factor restricting the therapeutic outcomes of various cancer types, including oral squamous cell carcinoma (OSCC). Therefore, exploring the key lncRNAs that regulate OSCC metastasis and elucidating their molecular mechanisms will facilitate the development of new strategies for effective OSCC therapy.

Methods
We analyzed the lncRNA expression profiles of tumor tissues from OSCC patients with and without cervical lymph node metastasis, and OSCC cell lines. We revealed high expression of oral squamous cell carcinoma metastasis-related lncRNA 1 (lncOCMRL1) in OSCC patient tumor tissues with lymph node metastasis and highly metastatic OSCC cell lines. The effects of lncOCMRL1 knockdown on the invasion, migration and proliferation abilities of OSCC cells were explored through qRT-PCR, Transwell, colony formation, and cell proliferation experiments. The mechanism by which lncOCMRL1 promotes OSCC metastasis and proliferation was explored through RNA pull-down, silver staining, mass spectrometry, RIP, and WB experiments. To increase its translational potential, we developed a reduction-responsive nanodelivery system to deliver siRNA for antitumor therapy.

Results
We determined that lncOCMRL1 is highly expressed in OSCC metastatic tumor tissues and cells. Functional studies have shown that high lncOCMRL1 expression can promote the growth and metastasis of OSCC cells both in vivo and in vitro. Mechanistically, lncOCMRL1 could induce epithelial-mesenchymal transition (EMT) via the suppression of RRM2 ubiquitination and thereby promote the proliferation, invasion, and migration of OSCC cells. We further constructed reduction-responsive nanoparticles (NPs) for the systemic delivery of siRNAs targeting lncOCMRL1 and demonstrated their high efficacy in silencing lncOCMRL1 expression in vivo and significantly inhibited OSCC tumor growth and metastasis.

Conclusions
Our results suggest that lncOCMRL1 is a reliable target for blocking lymph node metastasis in OSCC.
Targeting DNM1L/DRP1-FIS1 axis inhibits high-grade glioma progression by impeding mitochondrial respiratory cristae remodeling
Authors: Li Xiaodong , Tie Jingjing , Sun Yuze , Gong Chengrong , Deng Shizhou , Chen Xiyu , Li Shujiao , Wang Yaoliang , Wang Zhenhua , Wu Feifei , Liu Hui , Wu Yousheng , Zhang Guopeng , Guo Qingdong , Yang Yanling , Wang Yayun 
Published: September 2024

Abstract
Background
The dynamics of mitochondrial respiratory cristae (MRC) and its impact on oxidative phosphorylation (OXPHOS) play a crucial role in driving the progression of high-grade glioma (HGG). However, the underlying mechanism remains unclear.

Methods
In the present study, we employed machine learning-based transmission electron microscopy analysis of 7141 mitochondria from 54 resected glioma patients. Additionally, we conducted bioinformatics analysis and multiplex immunohistochemical (mIHC) staining of clinical glioma microarrays to identify key molecules involved in glioma. Subsequently, we modulated the expression levels of mitochondrial dynamic-1-like protein (DNM1L/DRP1), and its two receptors, mitochondrial fission protein 1 (FIS1) and mitochondrial fission factor (MFF), via lentiviral transfection to further investigate the central role of these molecules in the dynamics of glioblastoma (GBM) cells and glioma stem cells (GSCs). We then evaluated the potential impact of DNM1L/DRP1, FIS1, and MFF on the proliferation and progression of GBM cells and GSCs using a combination of CCK-8 assay, Transwell assay, Wound Healing assay, tumor spheroid formation assay and cell derived xenograft assay employing NOD/ShiLtJGpt-Prkdcem26Cd52Il2rgem26Cd22/Gpt (NCG) mouse model. Subsequently, we validated the ability of the DNM1L/DRP1-FIS1 axis to remodel MRC structure through mitophagy by utilizing Seahorse XF analysis technology, mitochondrial function detection, MRC abundance detection and monitoring dynamic changes in mitophagy.

Results
Our findings revealed that compared to low-grade glioma (LGG), HGG exhibited more integrated MRC structures. Further research revealed that DNM1L/DRP1, FIS1, and MFF played pivotal roles in governing mitochondrial fission and remodeling MRC in HGG. The subsequent validation demonstrated that DNM1L/DRP1 exerts a positive regulatory effect on FIS1, whereas the interaction between MFF and FIS1 demonstrates a competitive inhibition relationship. The down-regulation of the DNM1L/DRP1-FIS1 axis significantly impaired mitophagy, thereby hindering the remodeling of MRC and inhibiting OXPHOS function in glioma, ultimately leading to the inhibition of its aggressive progression. In contrast, MFF exerts a contrasting effect on MRC integrity, OXPHOS activity, and glioma progression.

Conclusions
This study highlights that the DNM1L/DRP1-FIS1 axis stabilizes MRC structures through mitophagy in HGG cells while driving their OXPHOS activity ultimately leading to robust disease progression. The inhibition of the DNM1L/DRP1-FIS1 axis hinders MRC remodeling and suppresses GBM progression. We propose that down-regulation of the DNM1L/DRP1-FIS1 axis could be a potential therapeutic strategy for treating HGG.
Views of research ethics committee members on end-of-participation communications for trial participants who stop taking part: a cross-sectional survey study
Authors: Cragg William J. , Bishop Liam , Gilberts Rachael , Gregg Michael , Mancini Mary , de Barros Clara Martins 
Published: September 2024

Abstract

Background
Giving information to trial participants who stop taking part could support them through what can be a difficult process. We previously developed guidance around the ethical acceptability of such information provision, and about how trialists can develop suitable communication materials. There is limited evidence about what research ethics committees think of this issue, and limited guidance about what level of oversight they should have over the proposed communications, or post-consent participant communications generally. We conducted a survey of UK ethics committee members to address these points.

Methods
The survey was co-developed by public contributors and trialists who had previously worked together on the communications guidance. We asked respondents if they agreed with the general idea of informing participants who stop taking part, if they had ever been requested to review similar communications, and what level of ethics committee review they might recommend. The survey was primarily conducted online. It was reviewed by three ethics committee members before finalisation and shared directly with all UK ethics committee members. We analysed quantitative questions descriptively and used inductive analysis for open questions to identify common themes.

Results
Ninety-one ethics committee members participated (nearly 10% of all UK members). The sample was similar to reported data about all members in terms of several personal characteristics. Most respondents (83%) agreed with our project’s rationale. Only 23% of respondents reported having been asked to review an end-of-participation information sheet before. Respondents gave various answers about the level of ethics committee review required, but most supported a relatively proportionate review process. Common concerns were about the risk of coercion or making participants feel pressured.

Conclusions
Our survey suggests that ethics committee members generally support providing information to trial participants who stop taking part, if risks to participants are mitigated. We believe our guidance already addresses the main concerns raised. Our respondents’ lack of prior experience with end-of-participation information sheets suggests that participants are not getting information they want or need when they stop participating. Our results help clarify how ethics committee should oversee post-consent participant communications, but further guidance from research regulators could be helpful.