bluuebunny/crossref_metadata_2025_split huggingface dataset:
The limitless endophytes: their role as antifungal agents against top priority pathogens
Authors: Moussa Ashaimaa Y. 
Published: May 2024

AbstractMulti resistant fungi are on the rise, and our arsenal compounds are limited to few choices in the market such as polyenes, pyrimidine analogs, azoles, allylamines, and echinocandins. Although each of these drugs featured a unique mechanism, antifungal resistant strains did emerge and continued to arise against them worldwide. Moreover, the genetic variation between fungi and their host humans is small, which leads to significant challenges in new antifungal drug discovery. Endophytes are still an underexplored source of bioactive secondary metabolites. Many studies were conducted to isolate and screen endophytic pure compounds with efficacy against resistant yeasts and fungi; especially, Candida albicans, C. auris, Cryptococcus neoformans and Aspergillus fumigatus, which encouraged writing this review to critically analyze the chemical nature, potency, and fungal source of the isolated endophytic compounds as well as their novelty features and SAR when possible. Herein, we report a comprehensive list of around 320 assayed antifungal compounds against Candida albicans, C. auris, Cryptococcus neoformans and Aspergillus fumigatus in the period 1980–2024, the majority of which were isolated from fungi of orders Eurotiales and Hypocreales associated with terrestrial plants, probably due to the ease of laboratory cultivation of these strains. 46% of the reviewed compounds were active against C. albicans, 23% against C. neoformans, 29% against A. fumigatus and only 2% against C. auris. Coculturing was proved to be an effective technique to induce cryptic metabolites absent in other axenic cultures or host extract cultures, with Irperide as the most promising compounds MIC value 1 μg/mL. C. auris was susceptible to only persephacin and rubiginosin C. The latter showed potent inhibition against this recalcitrant strain in a non-fungicide way, which unveils the potential of fungal biofilm inhibition. Further development of culturing techniques and activation of silent metabolic pathways would be favorable to inspire the search for novel bioactive antifungals.
Graphic abstract
N6-methyladenosine-modified SENP1, identified by IGF2BP3, is a novel molecular marker in acute myeloid leukemia and aggravates progression by activating AKT signal via de-SUMOylating HDAC2
Authors: Wen Diguang , Xiao Hang , Gao Yueyi , Zeng Hanqing , Deng Jianchuan 
Published: May 2024

Abstract
Background
Elevated evidence suggests that the SENPs family plays an important role in tumor progression. However, the role of SENPs in AML remains unclear.

Methods
We evaluated the expression pattern of SENP1 based on RNA sequencing data obtained from OHSU, TCGA, TARGET, and MILE datasets. Clinical samples were used to verify the expression of SENP1 in the AML cells. Lentiviral vectors shRNA and sgRNA were used to intervene in SENP1 expression in AML cells, and the effects of SENP1 on AML proliferation and anti-apoptosis were detected using in vitro and in vivo models. Chip-qPCR, MERIP-qPCR, CO-IP, RNA pulldown, and dual-luciferase reporter gene assays were used to explore the regulatory mechanisms of SNEP1 in AML.

Results
SENP1 was significantly upregulated in high-risk AML patients and closely related to poor prognosis. The AKT/mTOR signaling pathway is a key downstream pathway that mediates SENP1's regulation of AML proliferation and anti-apoptosis. Mechanistically, the CO-IP assay revealed binding between SENP1 and HDAC2. SUMO and Chip-qPCR assays suggested that SENP1 can desumoylate HDAC2, which enhances EGFR transcription and activates the AKT pathway. In addition, we found that IGF2BP3 expression was upregulated in high-risk AML patients and was positively correlated with SENP1 expression. MERIP-qPCR and RIP-qPCR showed that IGF2BP3 binds SENP1 3-UTR in an m6A manner, enhances SENP1 expression, and promotes AKT pathway conduction.

Conclusions
Our findings reveal a distinct mechanism of SENP1-mediated HDAC2-AKT activation and establish the critical role of the IGF2BP3/SENP1signaling axis in AML development.
Bifidobacterium adolescentis-derived hypaphorine alleviates acetaminophen hepatotoxicity by promoting hepatic Cry1 expression
Authors: Qin Ping , Li Yanru , Su Yangjing , Wang Ze , Wu Rong , Liang Xiaoqi , Zeng Yunong , Guo Peiheng , Yu Zhichao , Huang Xintao , Yang Hong , Zeng Zhenhua , Zhao Xiaoshan , Gong Shenhai , Han Jiaochan , Chen Zhongqing , Xiao Wei , Chen Ali 
Published: May 2024

AbstractAcetaminophen (APAP)-induced liver injury (AILI) is a pressing public health concern. Although evidence suggests that Bifidobacterium adolescentis (B. adolescentis) can be used to treat liver disease, it is unclear if it can prevent AILI. In this report, we prove that B. adolescentis significantly attenuated AILI in mice, as demonstrated through biochemical analysis, histopathology, and enzyme-linked immunosorbent assays. Based on untargeted metabolomics and in vitro cultures, we found that B. adolescentis generates microbial metabolite hypaphorine. Functionally, hypaphorine inhibits the inflammatory response and hepatic oxidative stress to alleviate AILI in mice. Transcriptomic analysis indicates that Cry1 expression is increased in APAP-treated mice after hypaphorine treatment. Overexpression of Cry1 by its stabilizer KL001 effectively mitigates liver damage arising from oxidative stress in APAP-treated mice. Using the gene expression omnibus (GEO) database, we verified that Cry1 gene expression was also decreased in patients with APAP-induced acute liver failure. In conclusion, this study demonstrates that B. adolescentis inhibits APAP-induced liver injury by generating hypaphorine, which subsequently upregulates Cry1 to decrease inflammation and oxidative stress.
Neutrophils cultured ex vivo from CD34+ stem cells are immature and genetically tractable
Authors: Naveh Claire A. , Roberts Kiran , Zakrzewski Przemysław , Rice Christopher M. , Ponce-Garcia Fernando M. , Fleming Kathryn , Thompson Megan , Panyapiean Nawamin , Jiang Huan , Diezmann Stephanie , Moura Pedro L. , Toye Ashley M. , Amulic Borko 
Published: May 2024

Abstract
Background
Neutrophils are granulocytes with essential antimicrobial effector functions and short lifespans. During infection or sterile inflammation, emergency granulopoiesis leads to release of immature neutrophils from the bone marrow, serving to boost circulating neutrophil counts. Steady state and emergency granulopoiesis are incompletely understood, partly due to a lack of genetically amenable models of neutrophil development.

Methods
We optimised a method for ex vivo production of human neutrophils from CD34+ haematopoietic progenitors. Using flow cytometry, we phenotypically compared cultured neutrophils with native neutrophils from donors experiencing emergency granulopoiesis, and steady state neutrophils from non-challenged donors. We carry out functional and proteomic characterisation of cultured neutrophils and establish genome editing of progenitors.

Results
We obtain high yields of ex vivo cultured neutrophils, which phenotypically resemble immature neutrophils released into the circulation during emergency granulopoiesis. Cultured neutrophils have similar rates of ROS production and bacterial killing but altered degranulation, cytokine release and antifungal activity compared to mature neutrophils isolated from peripheral blood. These differences are likely due to incomplete synthesis of granule proteins, as demonstrated by proteomic analysis.

Conclusion
Ex vivo cultured neutrophils are genetically tractable via genome editing of precursors and provide a powerful model system for investigating the properties and behaviour of immature neutrophils.
Therapeutic role of interferon-γ in experimental autoimmune encephalomyelitis is mediated through a tolerogenic subset of splenic CD11b+ myeloid cells
Authors: Arellano Gabriel , Acuña Eric , Loda Eileah , Moore Lindsay , Tichauer Juan E. , Castillo Cristian , Vergara Fabian , Burgos Paula I. , Penaloza-MacMaster Pablo , Miller Stephen D. , Naves Rodrigo 
Published: May 2024

AbstractCumulative evidence has established that Interferon (IFN)-γ has both pathogenic and protective roles in Multiple Sclerosis and the animal model, Experimental Autoimmune Encephalomyelitis (EAE). However, the underlying mechanisms to the beneficial effects of IFN-γ are not well understood. In this study, we found that IFN-γ exerts therapeutic effects on chronic, relapsing-remitting, and chronic progressive EAE models. The frequency of regulatory T (Treg) cells in spinal cords from chronic EAE mice treated with IFN-γ was significantly increased with no effect on Th1 and Th17 cells. Consistently, depletion of FOXP3-expressing cells blocked the protective effects of IFN-γ, indicating that the therapeutic effect of IFN-γ depends on the presence of Treg cells. However, IFN-γ did not trigger direct in vitro differentiation of Treg cells. In vivo administration of blocking antibodies against either interleukin (IL)-10, transforming growth factor (TGF)-β or program death (PD)-1, revealed that the protective effects of IFN-γ in EAE were also dependent on TGF-β and PD-1, but not on IL-10, suggesting that IFN-γ might have an indirect role on Treg cells acting through antigen-presenting cells. Indeed, IFN-γ treatment increased the frequency of a subset of splenic CD11b+ myeloid cells expressing TGF-β-Latency Associated Peptide (LAP) and program death ligand 1 (PD-L1) in a signal transducer and activator of transcription (STAT)-1-dependent manner. Furthermore, splenic CD11b+ cells from EAE mice preconditioned in vitro with IFN-γ and myelin oligodendrocyte glycoprotein (MOG) peptide exhibited a tolerogenic phenotype with the capability to induce conversion of naïve CD4+ T cells mediated by secretion of TGF-β. Remarkably, adoptive transfer of splenic CD11b+ cells from IFN-γ-treated EAE mice into untreated recipient mice ameliorated clinical symptoms of EAE and limited central nervous system infiltration of mononuclear cells and effector helper T cells. These results reveal a novel cellular and molecular mechanism whereby IFN-γ promotes beneficial effects in EAE by endowing splenic CD11b+ myeloid cells with tolerogenic and therapeutic activities.
Evaluating the process of practice enhancement for exclusive breastfeeding (PEEB): a participatory action research approach for clinical innovation
Authors: Lehane Elaine , Buckley Catherine , Mulcahy Helen , McCarthy Elizabeth , Cogan Liz , O’Connell Rhona , Murphy Margaret , Leahy-Warren Patricia 
Published: May 2024

Abstract
Background
Despite the known benefits of exclusive breastfeeding, global rates remain below recommended targets, with Ireland having one of the lowest rates in the world. This study explores the efficacy of Participatory Action Research (PAR) and Work-Based Learning Groups (WBLGs) to enhance breastfeeding practices within Irish healthcare settings from the perspective of WBLG participants and facilitators.

Methods
Employing a PAR approach, interdisciplinary healthcare professionals across maternity, primary, and community care settings (n = 94) participated in monthly WBLGs facilitated by three research and practice experts. These sessions, conducted over nine months (November 2021 – July 2022), focused on critical reflective and experiential learning to identify and understand existing breastfeeding culture and practices. Data were collected through participant feedback, facilitator notes, and reflective exercises, with analysis centered on participant engagement and the effectiveness of WBLGs. This approach facilitated a comprehensive understanding of breastfeeding support challenges and opportunities, leading to the development of actionable themes and strategies for practice improvement.

Results
Data analysis from WBLG participants led to the identification of five key themes: Empowerment, Ethos, Journey, Vision, and Personal Experience. These themes shaped the participants’ meta-narrative, emphasising a journey of knowledge-building and empowerment for breastfeeding women and supporting staff, underlining the importance of teamwork and multidisciplinary approaches. The project team’s evaluation highlighted four additional themes: Building Momentum, Balancing, Space Matters, and Being Present. These themes reflect the dynamics of the PAR process, highlighting the significance of creating a conducive environment for discussion, ensuring diverse engagement, and maintaining energy and focus to foster meaningful practice changes in breastfeeding support.

Conclusion
This study highlights the potential of WBLGs and PAR to enhance the understanding and approach of healthcare professionals towards breastfeeding support. By fostering reflective and collaborative learning environments, the study has contributed to a deeper understanding of the challenges in breastfeeding support and identified key areas for improvement. The methodologies and themes identified hold promise to inform future practice and policy development in maternal and child health.
Presentation and management of delayed bronchopleural fistula after pulmonary lobectomy: a case report
Authors: Jalil Riad Abdel , Dabous Ali , Khamees Almu’atasim , Alzu’bi Ahmad Yasin , Al-Majali Joud 
Published: May 2024

Abstract
Background
Lung cancer is the second most diagnosed cancer and the leading cause of cancer deaths worldwide. Surgical lung resection is the best treatment modality in the early stages of lung cancer as well as in some locally advanced cases. Postoperative air leak is one of the most common complications after pulmonary resection with incidence ranging between 20 and 33%. The majority of air leaks seal, within 5 days after surgery, on their own by conservative management. However, at least 5% of patients still have prolonged air coming out from the residual lung at discharge. This report describes the management of a thin lady with right lung cancer who underwent a right lower lobectomy and then suffered from a delayed air leak 7 weeks after surgery and required extensive thoracic and general surgery collaboration.

Case presentation
A 72-year-old heavy smoker female patient diagnosed with stage I lung cancer underwent right robotic-assisted thoracoscopic surgery converted to thoracotomy because of a fused fissure, right lower lobectomy, and mediastinal lymphadenectomy presented with delayed air leak 49 days after surgery. VATS decortication and mechanical pleurodesis were done 2 weeks after unsuccessful conservative treatment. Still, the lung failed to expand four weeks later so the patient was sent to surgery; she is underweight (BMI of 18) with not many options for a big flap to fill the chest cavity empty space. Accordingly; the decision was to use multiple pedicle flaps; omentum, intercostal muscle, and serratus anterior muscle to cover the bronchopleural fistulas and fill the pleural space in addition to mechanical and chemical pleurodesis. Full expansion of the lung was obtained. The patient was discharged on Post-Operative day 5 without remnant pneumothorax.

Conclusions
Air leaks After lobectomy usually presents directly postoperatively; various management options are available ranging from conservative and minimally invasive to major operative treatment. We presented what we believe was unusual delayed bronchopleural fistula post-lobectomy in a thin lady which demonstrates clearly how a delayed air leak was detected and how collaborative efforts were crucial for delivering high-quality, safe, and patient-centered care till treated and complete recovery.
Knockout mice with pituitary malformations help identify human cases of hypopituitarism
Authors: Martinez-Mayer Julian , Brinkmeier Michelle L. , O’Connell Sean P. , Ukagwu Arnold , Marti Marcelo A. , Miras Mirta , Forclaz Maria V. , Benzrihen Maria G. , Cheung Leonard Y. M. , Camper Sally A. , Ellsworth Buffy S. , Raetzman Lori T. , Pérez-Millán Maria I. , Davis Shannon W. 
Published: May 2024

AbstractBackgroundCongenital hypopituitarism (CH) and its associated syndromes, septo-optic dysplasia (SOD) and holoprosencephaly (HPE), are midline defects that cause significant morbidity for affected people. Variants in 67 genes are associated with CH, but a vast majority of CH cases lack a genetic diagnosis. Whole exome and whole genome sequencing of CH patients identifies sequence variants in genes known to cause CH, and in new candidate genes, but many of these are variants of uncertain significance (VUS).MethodsThe International Mouse Phenotyping Consortium (IMPC) is an effort to establish gene function by knocking-out all genes in the mouse genome and generating corresponding phenotype data. We used mouse embryonic imaging data generated by the Deciphering Mechanisms of Developmental Disorders (DMDD) project to screen 209 embryonic lethal and sub-viable knockout mouse lines for pituitary malformations.ResultsOf the 209 knockout mouse lines, we identified 51 that have embryonic pituitary malformations. These genes not only represent new candidates for CH, but also reveal new molecular pathways not previously associated with pituitary organogenesis. We used this list of candidate genes to mine whole exome sequencing data of a cohort of patients with CH, and we identified variants in two unrelated cases for two genes,MORC2andSETD5, with CH and other syndromic features.ConclusionsThe screening and analysis of IMPC phenotyping data provide proof-of-principle that recessive lethal mouse mutants generated by the knockout mouse project are an excellent source of candidate genes for congenital hypopituitarism in children.
Actinobacteria diversity associated with marine sediments and a wetland system, Agulhas-South Africa
Authors: Prins Alaric , Dyani Siphosethu S. , Vreulink Jo-Marie , Maldonado Luis A. , Le Roes-Hill Marilize 
Published: May 2024

Abstract
Background
South Africa is known for its great biodiversity. The Agulhas Plain represents one such unique environment where low-gradient topography has resulted in extensive wetland formation. It is fed by two major river systems, bringing in brackish, alkaline water. It has been exposed to major marine transgression and regression events, and harbours great Fynbos diversity as well as a Mediterranean-type climate, thereby creating unique ecosystems. It is therefore surprising that little is known about the bacterial diversity associated with the Agulhas Plain and associated marine ecosystems.

Methods
In this study, we focused on the actinobacterial diversity (Phylum Actinomycetota) associated with an emerging peatland on the Agulhas Plain (SF; Areas 1–3) and a marine site (ANP; Ocean, Rocky, Dry) located 10 km away from SF. A combined metataxanomics and isolation approach was taken to evaluate the actinobacterial diversity of the sampling sites and to determine the effect of environmental physicochemical parameters on these populations. Various genome analyses were performed on an Sva0096 marine bin to gain insight into its ecological role.

Results
Metataxanomics showed that the two sites shared defined major taxa, including Blastococcus, Geodermatophilus, Microbacterium, Mycobacterium, Nocardioides, Streptomyces, and the Sva0996 marine group. Analysis of the biosynthetic potential of an Sva0996 marine bin134 (obtained from GenBank) provided insights into the potential ecological role of this group of bacteria in both the marine and terrestrial environments. Higher actinobacterial diversity (Shannon index > 5) was observed for Areas 2 and 3 (SF), as well as the ANP Dry samples. The actinobacterial population composition was found to be driven by salinity, pH, Mn, and Ca, with certain areas of SF exhibiting similar (and even higher) salinity (SF: 70–100 Ω vs. ANP: 100–160 Ω) and lower pH levels (SF: 6.3-8.0 vs. ANP: 8.6–8.9) to that of the marine environment.

Conclusion
This snapshot study has provided some insights into the actinobacterial diversity of the two sites studied. Analysis of an Sva0096 marine bin134 provided further insights into the potential ability of the Sva0096 marine group to survive in a unique terrestrial environment that is periodically exposed to environmental pressures that mimic the marine environment.
Molecular subtypes of breast cancer identified by dynamically enhanced MRI radiomics: the delayed phase cannot be ignored
Authors: Huang Guoliang , Du Siyao , Gao Si , Guo Liangcun , Zhao Ruimeng , Bian Xiaoqian , Xie Lizhi , Zhang Lina 
Published: May 2024

Abstract
Objectives
To compare the diagnostic performance of intratumoral and peritumoral features from different contrast phases of breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) by building radiomics models for differentiating molecular subtypes of breast cancer.

Methods
This retrospective study included 377 patients with pathologically confirmed breast cancer. Patients were divided into training set (n = 202), validation set (n = 87) and test set (n = 88). The intratumoral volume of interest (VOI) and peritumoral VOI were delineated on primary breast cancers at three different DCE-MRI contrast phases: early, peak, and delayed. Radiomics features were extracted from each phase. After feature standardization, the training set was filtered by variance analysis, correlation analysis, and least absolute shrinkage and selection (LASSO). Using the extracted features, a logistic regression model based on each tumor subtype (Luminal A, Luminal B, HER2-enriched, triple-negative) was established. Ten models based on intratumoral or/plus peritumoral features from three different phases were developed for each differentiation.

Results
Radiomics features extracted from delayed phase DCE-MRI demonstrated dominant diagnostic performance over features from other phases. However, the differences were not statistically significant. In the full fusion model for differentiating different molecular subtypes, the most frequently screened features were those from the delayed phase. According to the Shapley additive explanation (SHAP) method, the most important features were also identified from the delayed phase.

Conclusions
The intratumoral and peritumoral radiomics features from the delayed phase of DCE-MRI can provide additional information for preoperative molecular typing. The delayed phase of DCE-MRI cannot be ignored.

Critical relevance statement
Radiomics features extracted and radiomics models constructed from the delayed phase of DCE-MRI played a crucial role in molecular subtype classification, although no significant difference was observed in the test cohort.

Key Points

The molecular subtype of breast cancer provides a basis for setting treatment strategy and prognosis.

The delayed-phase radiomics model outperformed that of early-/peak-phases, but no differently than other phases or combinations.

Both intra- and peritumoral radiomics features offer valuable insights for molecular typing.

Graphical Abstract