bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Post‐2020 Global Biodiversity Framework: How did we get here, and where do we go next?
Authors: Hughes Alice C. 
Published: February 2023

AbstractDecember 2022 finally saw the historic agreement of the Kunming‐Montreal Global Biodiversity Framework (KM‐GBF), a landmark framework that sets to halt and reverse global biodiversity loss by remedying the multifaceted drivers behind biodiversity declines around the planet. The KM‐GBF follows on from the Aichi targets, which aimed to prevent further biodiversity loss through a concerted effort between 2010 and 2020, but which were not successfully achieved. The KM‐GBF builds on the drivers of biodiversity losses rather than their outcomes and sets a suite of targeted and measurable actions to reconcile losses. Developing the framework faced considerable challenges, especially in the face of the coronavirus disease 2019 pandemic, and issues were often resolved at the very last moment. Consequently, compromises had to be made, useful elements were left out, or removed from the KM‐GBF to achieve consensus, and some will need to be reflected in other ways, or incorporated into indicators. The final agreed KM‐GBF includes 4 goals and 23 targets in addition to a package of annexes including a monitoring framework to set targets and benchmark progress. Particularly challenging issues included the flagship target of ‘30 × 30’ of protecting 30% of land, freshwater, coastal, and high‐sea in a representative way by 2030, which will require both new mechanisms and funding streams to enact effectively. Digital sequence information and funding mechanisms also presented major hurdles in the agreement of the KM‐GBF. Ultimately, the success of the new GBF depends on implementation and mainstreaming. New targets can only be achieved through the inclusion of all sectors, clear communication, and effective funding mechanisms to guide change and provide the means to implement it. Furthermore, while common but differentiated responsibility is crucial to implementation, impacts of inaction are disproportionate in developing economies, and more resources and support are needed to enable them to develop sustainably and meet targets. This highlights the urgent need for action if we are to achieve the new targets and secure a future for all life on earth.
Evaluating caregivers arrangement of infant sleeping environments in the home
Authors: Mery Jacqueline N. , Day‐Watkins Jessica , Schnell Lauren K. , Vladescu Jason C. 
Published: February 2023

AbstractSleep‐related infant deaths are one of the top causes of infant mortality in the United States. A few behavior analytic studies have examined behavioral skills training to teach adults to arrange safe infant sleeping environments. These studies were conducted in an analogue environment, and no data were collected outside the training setting. The purpose of the current study was to replicate and extend the extant literature. We taught caregivers to arrange safe infant sleeping environments in a community‐based organization. Thereafter, we assessed the feasibility and effectiveness of a technology‐based contingency management procedure to examine caregivers' adherence with arrangement of a safe sleeping environment for their newborns across a 2‐week period. As in previous studies, behavioral skills training resulted in positive outcomes, and follow‐up data suggested that the technology‐based contingency management procedure may be a promising approach to promoting adherence with infant sleeping environment recommendations.
Conditioned media from human pluripotent stem cell‐derived cardiomyocytes inhibit the growth and migration of lung cancer cells
Authors: Sadeghi Hanieh , Masoudi Mohamad , Torabi Parisa , Rezaeiani Siamak , Movahedi Fatemeh , Pahlavan Sara , Moradi Sharif 
Published: February 2023

AbstractConditioned media (CM) from various cell types contain significant levels of paracrine factors. Recently, therapeutic properties of CM derived from stem cells have been revealed. Based on the fact that heart cancer is extremely rarely, we hypothesized that the CM obtained from human pluripotent stem cell‐derived cardiomyocytes might inhibit cancer cell growth and survival. To this end, lung cancer cell line A549 along with human foreskin fibroblasts (HFF) were treated with serial concentrations of cardiomyocyte CM (CCM) or fibroblast CM (FCM). We found that CCM markedly reduced the viability of lung cancer cells, while FCM did not compromise the viability of neither cancer cells nor HFF cells. Furthermore, we determined an optimized CCM concentration, 30 mg/mL, at which the growth, clonogenicity, and migration of A549 and Calu6 lung cancer cell lines were substantially impaired, whereas FCM did not influence these properties. Moreover, lung cancer cells exhibited cell cycle regulation upon treatment with CCM and the rate of apoptosis was markedly increased by cardiomyocyte CM in both lung cancer cell lines tested. Finally, in response to CCM treatment, A549 and Calu6 cells expressed lower levels of antiapoptotic and stemness genes, but higher levels of proapoptotic genes. In conclusion, this study provides cellular and molecular evidence for the antitumor ability of secretome obtained from stem cell‐derived cardiomyocytes.
Structural and biochemical insights into FKBP51 as a Hsp90 co‐chaperone
Authors: Baischew Asat , Engel Sarah , Geiger Thomas M. , Taubert Martha C. , Hausch Felix 
Published: February 2023

AbstractThe FK506‐binding protein 51 (FKBP51) is a high‐molecular‐weight immunophilin that emerged as an important drug target for stress‐related disorders, chronic pain, and obesity. It has been implicated in a plethora of molecular pathways but remains best characterized as a co‐chaperone of Hsp90 in the steroid hormone receptor (SHR) maturation cycle. However, the mechanistic and structural basis for the regulation of SHRs by FKBP51 and the usually antagonistic function compared with its closest homolog FKBP52 remains enigmatic. Here we review recent structural and biochemical studies of FKBPs as regulators in the Hsp90 machinery. These advances provide important insights into the roles of FKBP51 and FKBP52 in SHR regulation.
Structural analysis of human G‐protein‐coupled receptor 17 ligand binding sites
Authors: Konda Mani Saravanan , Thiyagarajan Ramesh , Yli‐Harja Olli , Kandhavelu Meenakshisundaram , Murugesan Akshaya 
Published: February 2023

AbstractThe human G protein coupled membrane receptor (GPR17), the sensor of brain damage, is identified as a biomarker for many neurological diseases. In human brain tissue, GPR17 exist in two isoforms, long and short. While cryo‐electron microscopy technology has provided the structure of the long isoform of GPR17 with Gi complex, the structure of the short isoform and its activation mechanism remains unclear. Recently, we theoretically modeled the structure of the short isoform of GPR17 with Gi signaling protein and identified novel ligands. In the present work, we demonstrated the presence of two distinct ligand binding sites in the short isoform of GPR17. The molecular docking of GPR17 with endogenous (UDP) and synthetic ligands (T0510.3657, MDL29950) found the presence of two distinct binding pockets. Our observations revealed that endogenous ligand UDP can bind stronger in two different binding pockets as evidenced by glide and autodock vina scores, whereas the other two ligand's binding with GPR17 has less docking score. The analysis of receptor−UDP interactions shows complexes' stability in the lipid environment by 100 ns atomic molecular dynamics simulations. The amino acid residues VAL83, ARG87, and PHE111 constitute ligand binding site 1, whereas site 2 constitutes ASN67, ARG129, and LYS232. Root mean square fluctuation analysis showed the residues 83, 87, and 232 with higher fluctuations during molecular dynamics simulation in both binding pockets. Our findings imply that the residues of GPR17's two binding sites are crucial, and their interaction with UDP reveals the protein's hidden signaling and communication properties. Furthermore, this finding may assist in the development of targeted therapies for the treatment of neurological diseases.
Targeting first trimester trophoblast cell metabolism modulates its susceptibility to Zika virus infection
Authors: Kafer Diego , Marquez Agostina , Merech Fátima , Hauk Vanesa , Paparini Daniel , Ramhorst Rosanna , Leirós Claudia Pérez , Garcia Cybele , Vota Daiana 
Published: February 2023

AbstractIn the last 15 years Zika virus (ZIKV) caused several outbreaks of increasing scale in Micronesia, South Pacific islands, and more recently in the Caribbean and South America. The severity of the clinical presentation in neonates from pregnant women infected with ZIKV during the last outbreak supports the relevance of unraveling the mechanism of infection and viral persistence in the placenta with local viral isolates. Here, we investigated the relevance of trophoblast metabolic rewiring for viral multiplication and the role of the vasoactive intestinal peptide (VIP) as an endogenous factor associated with placental restriction to ZIKV infection at early pregnancy. Our in vitro model demonstrated that ZIKV triggers metabolic rewiring in first trimester cytotrophoblast‐derived cells by increasing glucose utilization as fuel to sustain its replication, decreasing long‐chain polyunsaturated fatty acid uptake, and promoting lipid droplets accumulation to favor its multiplication. Of note, variations in nutrient availability modulated viral spread in trophoblast cultures. The presence of VIP during trophoblast infection impaired ZIKV infective particle production and viral replication, restoring cell migration and metabolism. Moreover, the blockade of endogenous VIP signaling increased viral particle production and the viral entry receptor AXL expression. These results highlight the potential role of VIP as an endogenous antiviral factor related to trophoblast cell permissiveness to ZIKV infection at early pregnancy.
Endothelial PAR2 activation evokes resistance artery relaxation
Authors: Zhang Xun , Lee Matthew D. , Buckley Charlotte , Hollenberg Morley D. , Wilson Calum , McCarron John G. 
Published: February 2023

AbstractProtease‐activated receptor‐1 & ‐2 (PAR1 and PAR2) are expressed widely in cardiovascular tissues including endothelial and smooth muscle cells. PAR1 and PAR2 may regulate blood pressure via changes in vascular contraction or relaxation mediated by endothelial Ca2+ signaling, but the mechanisms are incompletely understood. By using single‐cell Ca2+ imaging across hundreds of endothelial cells in intact blood vessels, we explored PAR‐mediated regulation of blood vessel function using PAR1 and PAR2 activators. We show that PAR2 activation evoked multicellular Ca2+ waves that propagated across the endothelium. The PAR2‐evoked Ca2+ waves were temporally distinct from those generated by muscarinic receptor activation. PAR2 activated distinct clusters of endothelial cells, and these cells were different from those activated by muscarinic receptor stimulation. These results indicate that distinct cell clusters facilitate spatial segregation of endothelial signal processing. We also demonstrate that PAR2 is a phospholipase C‐coupled receptor that evokes Ca2+ release from the IP3‐sensitive store in endothelial cells. A physiological consequence of this PAR2 signaling system is endothelium‐dependent relaxation. Conversely, PAR1 activation did not trigger endothelial cell Ca2+ signaling nor relax or contract mesenteric arteries. Neither did PAR1 activators alter the response to PAR2 or muscarinic receptor activation. Collectively, these results suggest that endothelial PAR2 but not PAR1 evokes mesenteric artery relaxation by evoking IP3‐mediated Ca2+ release from the internal store. Sensing mediated by PAR2 receptors is distributed to spatially separated clusters of endothelial cells.
Bacillaene, sharp objects consist in the arsenal of antibiotics produced byBacillus
Authors: Miao Shuang , Liang Jianhao , Xu Yuan , Yu Guohui , Shao Mingwei 
Published: February 2023

AbstractBacillusspecies act as plant growth‐promoting rhizobacteria (PGPR) that can produce a large number of bioactive metabolites. Bacillaene, a linear polyketide/nonribosomal peptide produced byBacillusstrains, is synthesized by thetrans‐acyltransferase polyketide synthetase. The complexity of the chemical structure, particularity of biosynthesis, potent bioactivity, and the important role of competition makeBacillusan ideal antibiotic weapon to resist other microbes and maintain the optimal rhizosphere environment. This review provides an updated view of the structural features, biological activity, biosynthetic regulators of biosynthetic pathways, and the important competitive role of bacillaene duringBacillussurvival.
Platelet removal from human blood plasma improves detection of extracellular vesicle‐associated miRNA
Authors: Bracht Jillian W. P. , Los Mandy , van Eijndhoven Monique A. J. , Bettin Britta , van der Pol Edwin , Pegtel D. Michiel , Nieuwland Rienk 
Published: February 2023

AbstractHuman blood plasma prepared by centrifugation contains not only extracellular vesicles (EVs) but also platelets and erythrocyte ghosts (ery‐ghosts). Here we studied whether analysis of miRNA associated with plasma EVs (EV‐miRNA) is affected by the presence of platelets and ery‐ghosts. EDTA blood was collected from healthy donors (n = 3), and plasma was prepared by the centrifugation protocol recommended by the International Society on Thrombosis and Haemostasis (ISTH), and by a centrifugation protocol from an EV‐miRNA expert lab (non‐ISTH protocol). EVs were isolated from plasma by size‐exclusion chromatography CL‐2B (SEC2B), and concentrations of platelets, activated platelets, ery‐ghosts and EVs (150–1000 nm) were measured by calibrated flow cytometry. Two EV‐associated miRNAs (let7a‐5p and miR‐21‐5p), and one platelet‐associated miRNA (miR‐223‐3p), were measured by qRT‐PCR. Measurements were performed with and without filtration using 0.8 μm track‐etched filters to remove platelets and ery‐ghosts from plasma and EV‐enriched SEC fractions. Plasma prepared by both centrifugation protocols contained platelets and ery‐ghosts, which co‐migrated with EVs into the EV‐enriched SEC2B fractions. Filtration removed platelets and ery‐ghosts (>97%; p ≤ 0.05) and did not affect the EV concentrations (p > 0.17). The miRNA concentrations were 2–4‐fold overestimated due to the presence of platelets but not ery‐ghosts. Thus, filtration of human plasma is expected to improve comparability and reproducibility of quantitative EV‐miRNA studies. Therefore, we recommend to measure and report the plasma concentration of platelets for EV‐miRNA studies, and to filter plasma before downstream analyses or storage in biobanks.
Multicomponent synthesis of new 5‐thiourea‐4‐aza‐2,3 didehydropodophyllotoxins as potent cytotoxic agents
Authors: Nguyen Thi Thuy Hang , Nguyen Le Anh , Pham Minh Quan , Vo Ngoc Binh , Ngo Quoc Anh 
Published: February 2023

AbstractIn this report, we have described the concise elaboration of 12 novel 5‐thiourea‐4‐aza‐2,3‐didehydropodophyllotoxin‐derivatives by the unconventional multicomponent reaction was based on a catalyst‐free and atom‐economical method. The synthetic approach features methodology using sulfur element in thiourea synthesis. Cytotoxicity of compounds was evaluated for their inhibition rate of cell growth against two human tumor cell lines (MCF‐7 and Hep‐G2). Some new 5‐thiourea‐4‐aza‐2,3‐didehydropodophyllotoxin such as 15a, 15d, 15l exhibit very good cytotoxicity and much more stronger than their precursor 5 amino‐4‐aza‐2,3‐didehydropodophyllotoxin. The number and chemical characters of the Cα substituents of the thiourea group may have a decisive role in the activity of the molecules. Docking studies of the tested molecules proved that compound 15a, 15d, 15l exhibit high binding affinity toward human topoisomerase II beta in compare to the reference inhibitor, etoposide. Further dock pose analysis sugessted these molecules as potential inhibitors‐based on their key interaction with residues within binding site of the protein.
Evaluation and improvement of CuI‐mediated 11C‐cyanation
Authors: Ishii Hideki , Yamasaki Tomoteru , Okamura Toshimitsu , Zhang Yiding , Kurihara Yusuke , Ogawa Masanao , Nengaki Nobuki , Zhang Ming‐Rong 
Published: February 2023

CuI‐mediated 11C‐cyanation was evaluated by synthesizing [11C]perampanel ([11C]5) as a model compound and compared with previous reports. To a DMF solution with 5′‐(2‐bromophenyl)‐1′‐phenyl‐[2,3′‐bipyridin]‐6′(1′H)‐one (4) and CuI, [11C]NH4CN in a stream of ammonia/nitrogen (5:95, v/v) gas was bubbled. Subsequently, the reaction mixture was heated at 180°C for 5 min. After HPLC purification, [11C]5 was obtained in 7.2 ± 1.0% (n = 4) non‐decay corrected radiochemical yield with >99% radiochemical purity and a molar activity of 98 ± 28 GBq/μmol. In vivo evaluations of [11C]5 were performed using small animals. PET scans to check the kinetics of [11C]5 in the whole body of mice suggested that [11C]5 spreads rapidly into the brain, heart, and lungs and then accumulates in the small intestine. To evaluate the performance of CuI‐mediated 11C‐cyanation reaction, bromobenzene (6a) was selected as the model compound; however, it failed. Therefore, optimization of the reaction conditions has been performed, and consequently, the addition of K2CO3 and prolonging the reaction time improved the radiochemical yield about double. With this improved method, CuI‐mediated 11C‐cyanation of various (hetero)aromatic bromides was performed to exhibit the tolerance of most functional groups and to provide 11C‐cyanated products in good to moderate radiochemical yields.
Metastatic cutaneous squamous cell carcinoma to the parotid: Adjuvant radiotherapy and treatment outcomes
Authors: Hu Marcus , Kim Anna N. H. , Emeto Theophilus I. , Collins Michael , Chopping Andrea , Lin Charles 
Published: February 2023

AbstractIntroductionAdjuvant radiotherapy is an established component in the management of metastatic cutaneous squamous cell carcinoma (SCC) involving the parotid gland. Radiotherapy technique, dose and volumes are seldom described sufficiently to allow close examination. We report our treatment outcomes and focus on treatment‐related factors that affect outcomes in this cohort.MethodsWe performed a retrospective review of patients with metastatic cutaneous SCCs who underwent parotidectomy with or without ipsilateral neck dissection. All patients received adjuvant radiotherapy. Demographics, clinical data and treatment details were collected from an intuitional electronic database. Individual patient‐level radiotherapy technique, volumes and doses were reviewed.ResultsBetween July 2008 and July 2018, 60 patients met our inclusion criteria. Median follow‐up duration was 32.7 months. The mean age was 66.4 years. The majority of patients (49 patients) received full neck irradiation. The 2‐year and 5‐year loco‐regional failure‐free survival was 87% (95% confidence interval (CI): 0.74–0.93) and 71% (95% CI: 0.52, 0.83), respectively. The 2‐year and 5‐year overall survival was 76% (95% CI: 0.62, 0.85) and 60% (95% CI: 0.45, 0.72), respectively. There were 15 cases of loco‐regional failures, with 6 cases with dermal involvement. Lymphovascular invasion (LVI) was associated with higher loco‐regional failure (hazard ratio: 8.43, 95% CI: 1.85–38.39, P = 0.005) and cancer‐specific mortality (hazard ratio: 5.40, 95% CI: 1.40–20.87, P = 0.015). Treatment technique, intensity‐modulated radiation therapy (IMRT) vs 3D conformal radiotherapy (3D CRT), bolus use, perineural invasion (PNI) and surgical margins were not significantly associated with loco‐regional failure.ConclusionWe demonstrated high loco‐regional control rates with routine use of comprehensive adjuvant radiotherapy. The presence of LVI was identified as a strong predictor for recurrence. Further analysis will help to define optimal radiation dose and techniques.
Planning experience of new graduate radiation therapists in New Zealand
Authors: Chadwick Kate , Larsen Peter , Dungey Gay 
Published: February 2023

AbstractIntroductionThis research assessed the preparedness of new graduate radiation therapists (NGRTs) for the clinical practice of planning.MethodsA senior planner from each department and NGRTs who completed their degree in 2020 were surveyed after approximately 6 months of practice. Both were asked about NGRTs preparedness for practice and for feedback on the Bachelor of Radiation Therapy (BRT) planning curriculum. NGRTs were asked about body sites planned, how many plans they completed and planning techniques they had used. Senior planners were asked about their expectations of NGRTs in planning.ResultsNew graduate radiation therapists frequently planned using three‐dimensional conformal radiation therapy (3DCRT) or virtual simulation (VSim). Commonly planned body sites were those with palliative intent, radical breast and sites more frequently planned using 3DCRT. The departmental sign‐off process sometimes prevented them from generating VMAT plans. They suggested more VMAT teaching could be included in the BRT. Senior planners expected NGRTs to be able to plan using 3DCRT and VMAT/IMRT. They suggested more clinical workflow teaching in the BRT planning curriculum. The majority of NGRTs and senior planners felt the BRT prepared the NGRTs for clinical practice.ConclusionThe undergraduate degree is preparing NGRTs for clinical practice in planning. 3DCRT and VSim planning techniques remain a core role of NGRTs and a large proportion of clinical workload. NGRTs utilised their VMAT/IMRT planning skills less often during their initial period of practice, despite being expected to possess these skills. This is a challenge for the undergraduate curriculum and New Zealand departments as the clinical use of VMAT/IMRT continues to increase.