bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the potential of Rhizopus oryzae AUMC14899 as a novel endophytic fungus for the production of l-tyrosine and its biomedical applications
Authors: El-Zawawy Nessma A. , Ali Sameh Samir , Nouh Hoda S. 
Published: February 2023

Abstract
Background
A significant threat to the public's health is the rise in antimicrobial resistance among numerous nosocomial bacterial infections. This may be a detriment to present initiatives to enhance the health of immune-compromised patients. Consequently, attention has been devoted to exploring new bioactive compounds in the field of drug discovery from endophytes. Therefore, this study is the first on the production of l-tyrosine (LT) as a promising bio-therapeutic agent from endophytic fungi.

Results
A new endophytic fungal isolate has been identified for the first time as Rhizopus oryzae AUMC14899 from Opuntia ficus-indica (L.) and submitted to GenBank under the accession number MZ025968. Separation of amino acids in the crude extract of this fungal isolate was carried out, giving a higher content of LT, which is then characterized and purified. LT exhibited strong antibacterial and anti-biofilm activities against multidrug-resistant Gram-negative and Gram-positive bacteria. The recorded minimum inhibitory concentration (MIC) values ranged from 6 to 20 µg/ml. In addition, LT caused a strong reduction in biofilm formation and disrupted the preformed biofilm. Moreover, results indicated that LT supported cell viability, evidencing hemocompatibility and no cytotoxicity.

Conclusion
Our findings suggest that LT has potential as a therapeutic agent due to its potential antibacterial, anti-biofilm, hemocompatibility, and lack of cytotoxic activities, which may also increase the range of therapy options for skin burn infections, leading to the development of a novel fungal-based drug.
The role of LncRNAs in tumor immunotherapy
Authors: Pan Xuan , Li Chenchen , Feng Jifeng 
Published: February 2023

AbstractCancer immunotherapy is a major breakthrough in the history of tumor therapy in the last decade. Immune checkpoint inhibitors blocking CTLA-4/B7 or PD-1/PD-L1 pathways have greatly prolonged the survival of patients with different cancers. Long non-coding RNAs (lncRNAs) are abnormally expressed in tumors and play an important role in tumor immunotherapy through immune regulation and immunotherapy resistance. In this review, we summarized the mechanisms of lncRNAs in regulating gene expression and well-studied immune checkpoint pathways. The crucial regulatory function of immune-related lncRNAs in cancer immunotherapy was also described. Further understanding of the underlying mechanisms of these lncRNAs is of great importance to the development of taking lncRNAs as novel biomarkers and therapeutic targets for immunotherapy.
Status of malaria in pregnancy services in Madagascar 2010–2021: a scoping review
Authors: Malpass Ashley , Hansen Natasha , Dentinger Catherine M. , Youll Susan , Cotte Annett , Mattern Chiarella , Ravaoarinosy Aimée 
Published: February 2023

Abstract
Background
Malaria in pregnancy (MIP) increases the risk of poor maternal and infant outcomes. To reduce these risks, WHO recommends insecticide-treated net (ITN) use, intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP), and prompt case management. However, uptake of these interventions remains sub-optimal in Madagascar. A scoping review was conducted to determine the breadth and depth of information available during 2010–2021 about Madagascar’s MIP activities and to identify barriers and facilitators to MIP interventions uptake.

Methods
PubMed, Google Scholar, and USAID’s files (Development Experience Catalog) were searched using the terms “Madagascar AND pregnancy AND malaria,” and reports and materials from stakeholders were collected. Documents in English and French from 2010 to 2021 with data regarding MIP were included. Documents were systematically reviewed and summarized; results were captured in an Excel database.

Results
Of 91 project reports, surveys and published articles, 23 (25%) fell within the stated time period and contained relevant data on MIP activities in Madagascar and were categorized accordingly: eight (35%) quality of care, including health facility readiness, provider knowledge and commodity availability; nine (39%) care-seeking behaviour; and, six (26%) prevention of MIP. Key barriers were identified: nine articles mentioned SP stockouts; seven found limitations of provider knowledge, attitudes, and behaviours (KAB) regarding MIP treatment and prevention; and, one reported limited supervision. MIP care seeking and prevention barriers and facilitators included women’s KAB regarding MIP treatment and prevention, distance, wait times, poor service quality, cost, and/or unwelcoming providers. A 2015 survey of 52 health facilities revealed limited client access to antenatal care due to financial and geographic barriers; two 2018 surveys revealed similar findings. Self-treatment and care-seeking delays were reported even when distance was not a barrier.

Conclusion
Among the studies and reports on MIP in Madagascar, the scoping review frequently noted barriers that could be mitigated by reducing stockouts, improving provider knowledge and attitudes, refining MIP communication, and improving service access. There is a need for coordinated efforts to address the identified barriers is the key implication of the findings.
Convection-enhanced delivery of nanoencapsulated gene locoregionally yielding ErbB2/Her2-specific CAR-macrophages for brainstem glioma immunotherapy
Authors: Gao Lin , Shi Chongdeng , Yang Zhenmei , Jing Weiqiang , Han Maosen , Zhang Jing , Zhang Cai , Tang Chunwei , Dong Yuanmin , Liu Ying , Chen Chen , Jiang Xinyi 
Published: February 2023

AbstractLocoregional delivery of chimeric antigen receptor (CAR)-modified T (CAR-T) cells has emerged as a promising strategy for brain tumors. However, the complicated ex vivo cell manufacturing procedures and the rapid progression of the disease have limited its broader applications. Macrophages (MΦs) exhibit unique effector functions and a high degree of infiltration within the solid tumor microenvironment (TME), especially in the brain, where MΦs function as structural support, and the main immune effector cells of the CNS represent 5–12% of brain cells. Here, we report a synthetic universal DNA nanocarrier for in situ genetic editing of intratumoral MΦs with an ErbB2-specific CAR to direct their phagocytic activity towards tumors and subsequently initiate a locoregional antitumor immune response. Specifically, we demonstrated that when delivered locoregionally, the RP-182 peptide, located in the shell of a nanoparticle, targeted MΦs and reprogrammed M2-like tumor-associated macrophages (TAMs) to an antitumor M1-like phenotype. Subsequently, the CAR gene-laden DNA nanocomplex can be used to introduce ErbB2-targeted CAR, and the generated CAR-MΦs then act as “living” cures, thereby serially clearing the invasive tumor cells. Our work demonstrates a practical antitumor immunotherapy for brainstem gliomas (BSGs) that may be broadly applicable for patients suffering from other ErbB2-positive solid malignancies.
Monitoring heparin therapy: stability of two different anti-Xa assays using blood samples collected in citrate-containing and CTAD tubes
Authors: Gremillet Marion , Talon Laurie , Lebreton Aurélien , Sinegre Thomas 
Published: February 2023

Abstract
Background
Anti-factor Xa assays and activated partial thromboplastin time (aPTT) are mainly employed to monitor patients treated with heparins. According to the Clinical and Laboratory Standards Institute and the French Working Group on Haemostasis and Thrombosis, anti-factor Xa activity and aPTT should be tested within 2 h of blood sampling for unfractionated heparin (UFH) monitoring. However, discrepancies exist depending on the used reagents and collecting tubes. The study aim was to determine the stability of aPTT and anti-factor Xa measurements using blood samples collected in citrate-containing or citrate-theophylline-adenosine-dipyridamole (CTAD) tubes and stored for up to 6 h.

Methods
Patients receiving UFH or low molecular weight heparin (LMWH) were enrolled; aPTT and anti-factor Xa activity were tested using two different analyser/reagent pairs (Stago and reagent without dextran sulfate; Siemens and reagent with dextran sulfate) after 1, 4 and 6 h of sample storage as whole blood or as plasma.

Results
For UFH monitoring, comparable anti-factor Xa activity and aPTT results were obtained with both analyser/reagent pairs when samples were stored as whole blood before plasma isolation. With samples stored as plasma, anti-factor Xa activity and aPTT were not affected up to 6 h after sampling when using the Stago/no-dextran sulfate reagent pair. With the Siemens/dextran sulfate-containing reagent, aPTT was significantly altered after 4 h of storage. For LMWH monitoring, anti-factor Xa activity remained stable (whole blood and plasma) for at least 6 h. Results were comparable with citrate-containing and CTAD tubes.

Conclusions
Anti-factor Xa activity in samples stored as whole blood or plasma was stable for up to 6 h, regardless of the reagent (with/without dextran sulfate)/collection tube. Conversely, aPTT was more variable because other plasma parameters can influence its measure and complicate the interpretation of its variations after 4 h.
From pressure in the pipeline to accelerating ascension: a survey to understand professional experiences of and opportunities for Canadian women in the healthcare sector
Authors: Desveaux L. , Pirmohamed J. , Hussain-Shamsy N. , Gray C. Steele 
Published: February 2023

Abstract
Background
Much has been written about the state and persistent lack of progress regarding gender equity and the commonly referenced phenomenon of a ‘leaking pipeline’. This framing focuses attention on the symptom of women leaving the workforce, rather than the well-documented contributing factors of hindered recognition, advancement, and financial opportunities. While attention shifts to identifying strategies and practices to address gender inequities, there is limited insight into the professional experiences of Canadian women, specifically in the female-dominated healthcare sector.

Methods
We conducted a survey of 420 women working across a range of roles within healthcare. Frequencies and descriptive statistics were calculated for each measure as appropriate. For each respondent, two composite Unconscious Bias (UCB) scores were created using a meaningful grouping approach.

Results
Our survey results highlight three key areas of focus to move from knowledge to action, including (1) identifying the resources, structural factors, and professional network elements that will enable a collective shift towards gender equity; (2) providing women with access to formal and informal opportunities to develop the strategic relational skills required for advancement; and (3) restructuring social environments to be more inclusive. Specifically, women identified that self-advocacy, confidence building, and negotiation skills were most important to support development and leadership advancement.

Conclusions
These insights provide systems and organizations with practical actions they can take to support women in the health workforce amid a time of considerable workforce pressure.
BMAL1/p53 mediating bronchial epithelial cell autophagy contributes to PM2.5-aggravated asthma
Authors: Chen Shuai-Jun , Huang Yi , Yu Fan , Feng Xiao , Zheng Yuan-Yi , Li Qian , Niu Qian , Jiang Ye-Han , Zhao Li-Qin , Wang Meng , Cheng Pei-Pei , Song Lin-Jie , Liang Li-Mei , He Xin-Liang , Xiong Liang , Xiang Fei , Wang Xiaorong , Ma Wan-Li , Ye Hong 
Published: February 2023

AbstractBackgroundFine particulate matter (PM2.5) is associated with increased incidence and severity of asthma. PM2.5 exposure disrupts airway epithelial cells, which elicits and sustains PM2.5-induced airway inflammation and remodeling. However, the mechanisms underlying development and exacerbation of PM2.5-induced asthma were still poorly understood. The aryl hydrocarbon receptor nuclear translocator-like protein 1 (BMAL1) is a major circadian clock transcriptional activator that is also extensively expressed in peripheral tissues and plays a crucial role in organ and tissue metabolism.ResultsIn this study, we found PM2.5 aggravated airway remodeling in mouse chronic asthma, and exacerbated asthma manifestation in mouse acute asthma. Next, low BMAL1 expression was found to be crucial for airway remodeling in PM2.5-challenged asthmatic mice. Subsequently, we confirmed that BMAL1 could bind and promote ubiquitination of p53, which can regulate p53 degradation and block its increase under normal conditions. However, PM2.5-induced BMAL1 inhibition resulted in up-regulation of p53 protein in bronchial epithelial cells, then increased-p53 promoted autophagy. Autophagy in bronchial epithelial cells mediated collagen-I synthesis as well as airway remodeling in asthma.ConclusionsTaken together, our results suggest that BMAL1/p53-mediated bronchial epithelial cell autophagy contributes to PM2.5-aggravated asthma. This study highlights the functional importance of BMAL1-dependent p53 regulation during asthma, and provides a novel mechanistic insight into the therapeutic mechanisms of BMAL1.Graphic abstract
Not1 and Not4 inversely determine mRNA solubility that sets the dynamics of co-translational events
Authors: Allen George , Weiss Benjamin , Panasenko Olesya O. , Huch Susanne , Villanyi Zoltan , Albert Benjamin , Dilg Daniel , Zagatti Marina , Schaughency Paul , Liao Susan E. , Corden Jeff , Polte Christine , Shore David , Ignatova Zoya , Pelechano Vicent , Collart Martine A. 
Published: February 2023

Abstract
Background
The Ccr4-Not complex is mostly known as the major eukaryotic deadenylase. However, several studies have uncovered roles of the complex, in particular of the Not subunits, unrelated to deadenylation and relevant for translation. In particular, the existence of Not condensates that regulate translation elongation dynamics has been reported. Typical studies that evaluate translation efficiency rely on soluble extracts obtained after the disruption of cells and ribosome profiling. Yet cellular mRNAs in condensates can be actively translated and may not be present in such extracts.

Results
In this work, by analyzing soluble and insoluble mRNA decay intermediates in yeast, we determine that insoluble mRNAs are enriched for ribosomes dwelling at non-optimal codons compared to soluble mRNAs. mRNA decay is higher for soluble RNAs, but the proportion of co-translational degradation relative to the overall mRNA decay is higher for insoluble mRNAs. We show that depletion of Not1 and Not4 inversely impacts mRNA solubilities and, for soluble mRNAs, ribosome dwelling according to codon optimality. Depletion of Not4 solubilizes mRNAs with lower non-optimal codon content and higher expression that are rendered insoluble by Not1 depletion. By contrast, depletion of Not1 solubilizes mitochondrial mRNAs, which are rendered insoluble upon Not4 depletion.

Conclusions
Our results reveal that mRNA solubility defines the dynamics of co-translation events and is oppositely regulated by Not1 and Not4, a mechanism that we additionally determine may already be set by Not1 promoter association in the nucleus.
Digital peer-to-peer support programme for informal caregivers of people living with motor neuron disease: study protocol for a multi-centre parallel group, single-blinded (outcome assessor) randomised controlled superiority trial
Authors: Rose Louise , Thaventhiran Thilipan , Hobson Esther , Rogers Rebecca , James Kirsty , Chu Petrina , Carter Ben , Faull Christina , Saha Sian , Lee Jeong Su , Kaltsakas Georgios , McDermott Christopher , Ramsay Michelle 
Published: February 2023

Abstract
Background
Peer support is effective in improving psychological well-being of family caregivers of people with conditions such as dementia, cancer, and brain injury. However, there are limited data on effective psychological interventions for family caregivers of people living with motor neurone disease. Our objective is to evaluate the efficacy of a virtual peer support programme for improving caregiver psychological wellbeing and caregiving related outcomes.

Methods
We will conduct a multi-centre parallel group randomised controlled superiority trial. Using a multi-modal recruitment strategy, we will recruit informal caregivers from UK MND clinics, in-patient units, and hospices. We will randomise (1:1, stratified by gender) participants to either a 12-week virtual peer support programme or usual care comprising provision of online information resources publicly available via the MND Association website. Peer support programme elements will be delivered via a secure digital e-platform aTouchAway™ (Aetonix, Canada). Our target sample size is 160 (80 each arm). Our primary outcome is the Hospital Anxiety and Depression Scale (HADS) assessed at 12 weeks (primary endpoint). Secondary outcomes that will also be assessed at 12 weeks include the Zarit Burden Interview, Pearlin Mastery Scale, Personal Gain Scale, Positive Affect Scale, and the Brief COPE. Outcome assessors will be blinded to allocation. Tertiary outcomes include perceived usability (1 item 9-point Likert scale) and acceptability (semi-structured qualitative interviews) of the peer support programme. Intervention fidelity measures will comprise frequency, type (text, audio, video), and duration (audio and video) of peer support contact downloaded from the aTouchAway AWS server. We will use a mixed-effects linear model to test the effect of the intervention on the primary outcome. Secondary outcomes will be analysed using linear regression. We have ethical approval (21/NW/0269) from the North-West Research Ethics Committee, UK.

Discussion
This single-blinded randomised controlled trial will determine the effect of a virtual peer support programme on caregiver psychological wellbeing and caregiver burden. This study will examine the impact of a virtual peer support intervention on quality-of-life measures in informal caregivers of individuals with MND living in the community.

Trial registration
ClinicalTrials.gov: NCT04695210
Development of a TaqMan qPCR assay for trypanosomatid multi-species detection and quantification in insects
Authors: Barranco-Gómez Olga , De Paula Jessica Carreira , Parada Jennifer Solano , Gómez-Moracho Tamara , Marfil Ana Vic , Zafra María , Orantes Bermejo Francisco José , Osuna Antonio , De Pablos Luis Miguel 
Published: February 2023

Abstract
Background
Trypanosomatid parasites are widely distributed in nature and can have a monoxenous or dixenous life-cycle. These parasites thrive in a wide number of insect orders, some of which have an important economic and environmental value, such as bees. The objective of this study was to develop a robust and sensitive real-time quantitative PCR (qPCR) assay for detecting trypanosomatid parasites in any type of parasitized insect sample.

Methods
A TaqMan qPCR assay based on a trypanosomatid-conserved region of the α-tubulin gene was standardized and evaluated. The limits of detection, sensitivity and versatility of the α-tubulin TaqMan assay were tested and validated using field samples of honeybee workers, wild bees, bumblebees and grasshoppers, as well as in the human infective trypanosomatid Leishmania major.

Results
The assay showed a detection limit of 1 parasite equivalent/µl and successfully detected trypanosomatids in 10 different hosts belonging to the insect orders Hymenoptera and Orthoptera. The methodology was also tested using honeybee samples from four apiaries (n = 224 worker honeybees) located in the Alpujarra region (Granada, Spain). Trypanosomatids were detected in 2.7% of the honeybees, with an intra-colony prevalence of 0% to 13%. Parasite loads in the four different classes of insects ranged from 40.6 up to 1.1 × 108 cell equivalents per host.

Conclusions
These results show that the α-tubulin TaqMan qPCR assay described here is a versatile diagnostic tool for the accurate detection and quantification of trypanosomatids in a wide range of environmental settings.

Graphical Abstract
Emerging role of mesenchymal stem/stromal cells (MSCs) and MSCs-derived exosomes in bone- and joint-associated musculoskeletal disorders: a new frontier
Authors: Gerami Mohammad Hadi , Khorram Roya , Rasoolzadegan Soheil , Mardpour Saeid , Nakhaei Pooria , Hashemi Soheyla , Al-Naqeeb Bashar Zuhair Talib , Aminian Amir , Samimi Sahar 
Published: February 2023

AbstractExosomes are membranous vesicles with a 30 to 150 nm diameter secreted by mesenchymal stem/stromal cells (MSCs) and other cells, such as immune cells and cancer cells. Exosomes convey proteins, bioactive lipids, and genetic components to recipient cells, such as microRNAs (miRNAs). Consequently, they have been implicated in regulating intercellular communication mediators under physiological and pathological circumstances. Exosomes therapy as a cell-free approach bypasses many concerns regarding the therapeutic application of stem/stromal cells, including undesirable proliferation, heterogeneity, and immunogenic effects. Indeed, exosomes have become a promising strategy to treat human diseases, particularly bone- and joint-associated musculoskeletal disorders, because of their characteristics, such as potentiated stability in circulation, biocompatibility, low immunogenicity, and toxicity. In this light, a diversity of studies have indicated that inhibiting inflammation, inducing angiogenesis, provoking osteoblast and chondrocyte proliferation and migration, and negative regulation of matrix-degrading enzymes result in bone and cartilage recovery upon administration of MSCs-derived exosomes. Notwithstanding, insufficient quantity of isolated exosomes, lack of reliable potency test, and exosomes heterogeneity hurdle their application in clinics. Herein, we will deliver an outline respecting the advantages of MSCs-derived exosomes-based therapy in common bone- and joint-associated musculoskeletal disorders. Moreover, we will have a glimpse the underlying mechanism behind the MSCs-elicited therapeutic merits in these conditions.