bluuebunny/crossref_metadata_2025 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

December 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

Sleep‐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

Conditioned 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

The 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

The 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

In 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

Protease‐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

Bacillusspecies 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

Human 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

In 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

Introduction

Adjuvant 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.

Methods

We 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.

Results

Between 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.

Conclusion

We 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

Introduction

This research assessed the preparedness of new graduate radiation therapists (NGRTs) for the clinical practice of planning.

Methods

A 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.

Results

New 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.

Conclusion

The 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.
Genetic basis of sleep phenotypes and rare neurodevelopmental syndromes reveal shared molecular pathways
Authors: Moysés‐Oliveira Mariana , Paschalidis Mayara , Souza‐Cunha Lais A. , Esteves‐Guerreiro Pedro A. , Adami Luana Nayara Gallego , Kloster Anna K. , Mosini Amanda C. , Moreira Gustavo A. , Doria Sandra , Tempaku Priscila F. , Pires Gabriel N. , Andersen Monica L. , Tufik Sergio
Published: February 2023

Sleep‐related phenotypes have been frequently reported in early on‐set epileptic encephalopathies and in developmental delay syndromes, in particular in syndromes related to autism spectrum disorder. Yet the convergent pathogenetic mechanisms between these comorbidities are largely unknown. We first performed a gene enrichment study that identified shared risk genes among rare epileptic encephalopathies/neurodevelopmental disorders, rare developmental delay genetic syndromes and sleep disturbances. We then determined cellular and molecular pathways enriched among genes shared between sleep phenotypes and those two early onset mental illnesses, aiming to identify genetic disparities and commonalities among these phenotypic groups. The sleep gene set was observed as significantly overlapped with the two gene lists associated to rare genetic syndromes (i.e., epileptic encephalopathies/neurodevelopmental disorders and developmental delay gene sets), suggesting shared genetic contribution. Similarities across significantly enriched pathways between the two intersect lists comprehended mostly synapse‐related pathways, such as retrograde endocannabinoid signaling, serotonergic, and GABAergic synapse. Network analysis indicates epileptic encephalopathies/neurodevelopmental disorders versus sleep‐specific clusters and developmental delay versus sleep‐specific clusters related to synaptic and transcriptional regulation, respectively. Longstanding functional patterns previously described in epileptic encephalopathies and neurodevelopmental disorders genetic architecture were recaptured after dissecting the overlap between the genes associated to those developmental phenotypes and sleep disturbances, suggesting that during neurodevelopment different molecular and functional mechanisms are related to alterations on circadian rhythm. The overlapping gene set and biological pathways highlighted by this study may serve as a primer for new functional investigations of shared molecular mechanisms between sleep disturbances and rare developmental syndromes.
How deadline orientation and architectural modularity influence software quality and job satisfaction
Authors: Kude Thomas , Foerderer Jens , Mithas Sunil , Heinzl Armin
Published: February 2023

The implementation of digital transformation programs requires careful allocation of software developers to a variety of digital products and services with different levels of modularity. This paper investigates how deadline orientation (an individual‐level preference of developers for completing work close to deadlines) and architectural modularity (a characteristic of products) influence central outcomes in software development. We argue that architectural modularity positively interacts with deadline orientation to influence software quality and the job satisfaction of developers. Our empirical analyses, using rare and high‐quality data from 131 software developers and 29 product owners working at a captive software development center in India of a leading global software firm, confirm our hypotheses. We contribute to the literature on software development by showing that the fit between the technological characteristics of the software product (i.e., architectural modularity) and people factors (i.e., the temporal work style preferences of developers) plays an important role in shaping both software quality and job satisfaction. Our study has wider implications for the literature on software development, temporal work styles, and architectural modularity. It is instructive for practitioners tasked with hiring or allocating software developers for software products with varying technological characteristics in their digital transformation efforts.
Silicon mitigates the negative impacts of salt stress in soybean plants
Authors: Peña‐Calzada Kolima , Olivera‐Viciedo Dilier , Calero‐Hurtado Alexander , de Mello Prado Renato , Habermann Eduardo , Lata Tenesaca Luis Felipe , Ajila Gabriela , de Oliveira Reginaldo , Rodríguez Juan Carlos , Lupino Gratão Priscila
Published: February 2023

BACKGROUND

Soybean is widely cultivated around the world, including regions with salinity conditions. Salt stress impairs plant physiology and growth, but recent evidence suggests that silicon (Si) is able to mitigate this stressful condition. Therefore, the purpose of this study was to evaluate how different strategies of Si application impact on salt stress tolerance of an intermediate Si accumulator species (soybean). Therefore, we applied four treatments: Si‐untreated plants (Si 0); foliar spraying at 20 mmol L−1 (Si F); nutritive solution addition at 2.0 mol L−1 (Si R), and combined foliar spraying at 20 mmol L−1 plus nutritive solution at 2.0 mmol L−1 (Si F + R). We investigated how Si application modified growth, leaf gas exchange, photosynthetic pigments, chlorophyll fluorescence, relative water content (RWC), nutrient accumulation, and ion homeostasis of soybean plants submitted to different levels of salt stress (50 and 100 mmol L−1 NaCl).

RESULTS

Salinity induced an expressive reduction in ion accumulation, plant water status, and growth of soybean, while Si application promoted contrary effects and increased potassium (K+) accumulation, water status, photosynthetic pigment content, chlorophyll fluorescence parameters, and gas exchange attributes. Additionally, Si application enhanced Si accumulation associated with decreased Na+ uptake and improved morpho‐physiological growth.

CONCLUSION

The use of exogenous Si can be an efficient strategy to attenuate the harmful effects of salt stress in soybean plants. The best application strategy was observed with combined foliar spraying with Si included in the nutritive solution (Si F + R). © 2023 Society of Chemical Industry.
Tumor deposits are associated with a higher risk of peritoneal disease in non‐metastatic colorectal cancer patients
Authors: Khan Hamza , Radomski Shannon N. , Siddiqi Amn , Zhou Nancy , Paneitz Dane C. , Johnston Fabian M. , Greer Jonathan B.
Published: February 2023

Background and Objectives

Tumor deposit (TD) is a poor prognostic factor in colorectal cancer (CRC) patients. This study aimed to determine whether TD carry the same risk of peritoneal recurrence as known high‐risk (HR) features in CRC patients.

Methods

A retrospective cohort‐study of stage I−III CRC patients from 2010 to 2015 was conducted. TD group was defined by the presence of TD on histopathology whereas HR group was defined by the presence of obstruction, perforation, or T4‐stage.

Results

A total of 151 patients with CRC were identified, of which 50 had TD and 101 had a HR feature. The overall risk of peritoneal recurrence was higher in the TD group versus HR group (36.0% vs. 19.8%, p = 0.03). The risk of peritoneum as the site of first recurrence was also higher in the TD group (22.0% vs. 12.9%, p = 0.03). Overall cancer recurrence at any site was also higher in the TD group (56.0% vs. 34.7%, p = 0.01). Median time to first recurrence was 1.2 (0.7−1.9) years in the TD group compared to 1.4 (0.8−2.1) years in the HR group (p = 0.31).

Conclusions

In non‐metastatic CRC patients, TD might have a higher risk of tumor recurrence versus their HR counterparts. Alternative strategies for surveillance and treatment should be considered.
Socioeconomic status, mental health, and nutrition are the principal traits for low back pain phenotyping: Data from the osteoarthritis initiative
Authors: Huang ZeYu , Guo Weihua , Martin John T.
Published: February 2023

Background

Low back pain (LBP) is a heterogeneous disease with biological, physical, and psychosocial etiologies. Models for predicting LBP severity and chronicity have not made a clinical impact, perhaps due to difficulty deciphering multidimensional phenotypes. In this study, our objective was to develop a computational framework to comprehensively screen metrics related to LBP severity and chronicity and identify the most influential.

Methods

We identified individuals from the observational, longitudinal Osteoarthritis Initiative cohort (N = 4796) who reported LBP at enrollment (N = 215). OAI descriptor variables (N = 1190) were used to cluster individuals via unsupervised learning and uncover latent LBP phenotypes. We also developed a dimensionality reduction algorithm to visualize clusters/phenotypes using Uniform Manifold Approximation and Projection (UMAP). Next, to predict chronicity, we identified those with acute LBP (N = 40) and persistent LBP over 8 years of follow‐up (N = 66) and built logistic regression and supervised machine learning models.

Results

We identified three LBP phenotypes: a “high socioeconomic status, low pain severity group”, a “low socioeconomic status, high pain severity group”, and an intermediate group. Mental health and nutrition were also key clustering variables, while traditional biomedical factors (e.g., age, sex, BMI) were not. Those who developed chronic LBP were differentiated by higher pain interference and lower alcohol consumption (a correlate to poor physical fitness and lower soceioeconomic status). All models for predicting chronicity had satisfactory performance (accuracy 76%–78%).

Conclusions

We developed a computational pipeline capable of screening hundreds of variables and visualizing LBP cohorts. We found that socioeconomic status, mental health, nutrition, and pain interference were more influential in LBP than traditional biomedical descriptors like age, sex, and BMI.
Potential of Lesion‐to‐Fat Elasticity Ratio Measured by Shear Wave Elastography to Reduce Benign Biopsies in BI‐RADS 4 Breast Lesions
Authors: Togawa Riku , Pfob André , Büsch Christopher , Alwafai Zaher , Balleyguier Corinne , Clevert Dirk‐André , Duda Volker , Fastner Sarah , Goncalo Manuela , Gomez Christina , Gruber Ines , Hahn Markus , Hennigs André , Kapetas Panagiotis , Nees Juliane , Ohlinger Ralf , Riedel Fabian , Rutten Matthieu , Schäfgen Benedikt , Stieber Anne , Tozaki Mitsuhiro , Wojcinski Sebastian , Rauch Geraldine , Heil Jörg , Barr Richard , Golatta Michael
Published: February 2023

Objectives

We evaluated whether lesion‐to‐fat ratio measured by shear wave elastography in patients with Breast Imaging Reporting and Data System (BI‐RADS) 3 or 4 lesions has the potential to further refine the assessment of B‐mode ultrasound alone in breast cancer diagnostics.

Methods

This was a secondary analysis of an international diagnostic multicenter trial (NCT02638935). Data from 1288 women with breast lesions categorized as BI‐RADS 3 and 4a–c by conventional B‐mode ultrasound were analyzed, whereby the focus was placed on differentiating lesions categorized as BI‐RADS 3 and BI‐RADS 4a. All women underwent shear wave elastography and histopathologic evaluation functioning as reference standard. Reduction of benign biopsies as well as the number of missed malignancies after reclassification using lesion‐to‐fat ratio measured by shear wave elastography were evaluated.

Results

Breast cancer was diagnosed in 368 (28.6%) of 1288 lesions. The assessment with conventional B‐mode ultrasound resulted in 53.8% (495 of 1288) pathologically benign lesions categorized as BI‐RADS 4 and therefore false positives as well as in 1.39% (6 of 431) undetected malignancies categorized as BI‐RADS 3. Additional lesion‐to‐fat ratio in BI‐RADS 4a lesions with a cutoff value of 1.85 resulted in 30.11% biopsies of benign lesions which correspond to a reduction of 44.04% of false positives.

Conclusions

Adding lesion‐to‐fat ratio measured by shear wave elastography to conventional B‐mode ultrasound in BI‐RADS 4a breast lesions could help reduce the number of benign biopsies by 44.04%. At the same time, however, 1.98% of malignancies were missed, which would still be in line with American College of Radiology BI‐RADS 3 definition of <2% of undetected malignancies.
Reforestation, livelihoods and income equality: Lessons learned from China's Conversion of Cropland to Forest Program
Authors: Moioli Camilla , Shrestha Anil , Roeser Dominik , Wang Guangyu , Sunderland Terry , Zerriffi Hisham
Published: February 2023

Despite global momentum in restoration activities, their socio‐economic implications are little studied. Thus far, the limited evidence available tends to overlook equity and equality outcomes. In this work, we aimed at investigating fairness within the Chinese Conversion of Cropland to Forest Program (CCFP), given the relevance of local people's support for the long‐term success of land restoration and for the inherent belief that equity should be pursued also by environmental policies. Additionally, we propose a methodology to investigate equity and equality, from a quantitative perspective. Our results suggested a shift in the overall households' economic structure, with the main changes being a decrease in farming activities (−44 pp) and a sharp increase in out‐migration (+44 pp), with the most significant variation within the lowest income groups (−57 pp and + 75 pp, respectively). We also observed that both equality (the Gini coefficient decreased by 23%) and equity (higher income increase for low‐income groups) improved, and the best enhancement happened in the regions where the CCFP has been implemented for a longer time. Moreover, data showed that the main driver of inequality was households' income deriving from remittances, both before and after the Program implementation (with concentration coefficient equal to 1.1 and 1.0, respectively) but its effect decreased over time suggesting an increase in out‐migration opportunities for lower‐income households. Finally, we found that the level of participation in the Program holds a quite strong explanatory power for both on‐farm and off‐farm income (explaining 19% and 18% of their respective variability).
Prevalence of otolaryngological disease in a refugee population compared to US‐born patients
Authors: Jaradeh Katrin , Tang Alice , Czechowicz Josephine A. , Jacobson Lia , Raphael Eva
Published: February 2023

Objective

Limited data exists regarding otolaryngological (ENT) disease in refugees and we aim to characterize its prevalence.

Methods

This is a retrospective descriptive chart review of adult US‐born, immigrant, and refugee patients receiving care at a primary care clinic between 2014 and 2017. We report the prevalence of ENT disease by immigration status. Bivariable and multivariable logistic regression models were conducted to assess differences in prevalence of ENT disease by immigration status.

Results

Of 995 patients included, 202 US‐born, 450 immigrants, and 343 were refugees. Immigrants were older (46 years vs. 34 years among refugees, 35.5 years among US‐born, p < .001) and more likely to be women (64% vs. 52% among refugees and 56% among US‐born, p = .003). Among refugees, 27% were Central American, 22% Chinese, and 9.3% Middle Eastern. Hearing loss and allergic rhinitis were the top two diagnoses among the three groups of immigration status. More refugees had at least 1 ENT diagnosis compared to the other groups (16% vs 14% among immigrants and 6% US‐born, p < .001). Refugees were more likely to have at least 1 ENT diagnosis compared to US‐born individuals (age and gender adjusted [aOR] 3.40, 95% CI [1.80–6.95], p < .001) and immigrants (aOR 1.62, [1.05–2.51], p = .03).

Conclusion

ENT disease is prevalent among refugees, necessitating standardized evaluation during refugee health assessments and identifying barriers to referral and treatment.

Level of evidence

2b.
Dy3+ Doped All‐Inorganic Perovskite Nanocrystals Glass toward High‐Performance and High‐Stability Silicon Photodetectors
Authors: Hao Mengyang , Cheng Shun , He Ye , Xiang Weidong , Ding Nan , Xu Wen , Ma Chong‐Geng , Liang Xiaojuan
Published: February 2023

Silicon (Si) photodetectors (PDs) have attracted more attention due to their wide applications, but are limited by their extremely weak ultraviolet (UV) photo‐response. Herein, Dy3+‐CsPbCl2Br1 nanocrystals glass (Dy3+‐CPCB NCsG) is synthesized in borosilicate glass by traditional melt‐quenching. The doping of Dy3+ exceedingly improves the PL intensity of CsPbCl2Br1 nanocrystals glass (CPCB NCsG) with enhancing photoluminescence quantum yield from 8.0% to 30.2%, ascribed to the improved crystallinity and reduced defects. Meanwhile, the stability of CPCB NCsG exposed to air, light, and high temperature is largely boosted. After integrating with Dy3+‐CPCB NCsG, the responsivity, external quantum efficiency, detectivity, and stability of Si PDs are significantly enhanced. The responsivity (R) of Si PDs‐5% Dy3+‐CPCB NCsG is 0.006 A W−1 at 320 nm, which is sixfold higher than that of bare Si PDs. This work develops a blue Dy3+‐CPCB NCsG, which has great potential as a new luminescent material for the next generation of Si PDs.
Reaction between 1,3,5‐Triisopropylbenzene and Elemental Sulfur Extending the Scope of Reagents in Inverse Vulcanization
Authors: Lai Yue‐Sheng , Liu Ying‐Ling
Published: February 2023

Inverse vulcanization utilizes an organic compound as reagent for crosslinking elemental sulfur to result in corresponding polymeric material with a high sulfur content. This work, employing 1,3,5‐triisopropylbenzene (TIPB) as the reagent, demonstrates the first attempt on extending the scope of crosslinking agents of inverse vulcanization to saturate compounds. Under nuclear magnetic spectroscopic analysis, the reactions between TIPB and elemental sulfur take places through ring‐opening reaction of S8 resulting in sulfur radicals at sulfur chain ends, radicals transferring to isopropyl groups of TIPB, and radical coupling reactions between carbon radicals and sulfur radicals. The obtained products are similar to the sulfur polymers from conventional inverse vulcanization processes and show self‐healing property.
Statin Use and Incidence of Parkinson's Disease in Women from the French E3N Cohort Study
Authors: Nguyen Thi Thu Ha , Fournier Agnès , Courtois Émeline , Artaud Fanny , Escolano Sylvie , Tubert‐Bitter Pascale , Boutron‐Ruault Marie‐Christine , Degaey Isabelle , Roze Emmanuel , Canonico Marianne , Ahmed Ismaïl , Thiébaut Anne C.M. , Elbaz Alexis
Published: February 2023

Background

Statins represent candidates for drug repurposing in Parkinson's disease (PD). Few studies examined the role of reverse causation, statin subgroups, and dose–response relations based on time‐varying exposures.

Objectives

We examined whether statin use is associated with PD incidence while attempting to overcome the limitations described previously, especially reverse causation.

Method

We used data from the E3N cohort study of French women (follow‐up, 2004–2018). Incident PD was ascertained using multiple sources and validated by experts. New statin users were identified through linked drug claims. We set up a nested case‐control study to describe trajectories of statin prescriptions and medical consultations before diagnosis. We used time‐varying multivariable Cox proportional hazards regression models to examine the statins–PD association. Exposure indexes included ever use, cumulative duration/dose, and mean daily dose and were lagged by 5 years to address reverse causation.

Results

The case‐control study (693 cases, 13,784 controls) showed differences in case‐control trajectories, with changes in the 5 years before diagnosis in cases. Of 73,925 women (aged 54–79 years), 524 developed PD and 11,552 started using statins in lagged analyses. Ever use of any statin was not associated with PD (hazard ratio [HR] = 0.87, 95% confidence interval [CI] = 0.67–1.11). Alternatively, ever use of lipophilic statins was significantly associated with lower PD incidence (HR = 0.70, 95% CI = 0.51–0.98), with a dose–response relation for the mean daily dose (P‐linear trend = 0.02). There was no association for hydrophilic statins.

Conclusion

Use of lipophilic statins at least 5 years earlier was associated with reduced PD incidence in women, with a dose–response relation for the mean daily dose. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Contouring quality assurance methodology based on multiple geometric features against deep learning auto‐segmentation
Authors: Duan Jingwei , Bernard Mark E. , Castle James R. , Feng Xue , Wang Chi , Kenamond Mark C. , Chen Quan
Published: February 2023

Background

Contouring error is one of the top failure modes in radiation treatment. Multiple efforts have been made to develop tools to automatically detect segmentation errors. Deep learning‐based auto‐segmentation (DLAS) has been used as a baseline for flagging manual segmentation errors, but those efforts are limited to using only one or two contour comparison metrics.

Purpose

The purpose of this research is to develop an improved contouring quality assurance system to identify and flag manual contouring errors.

Methods and materials

DLAS contours were used as a reference to compare with manually segmented contours. A total of 27 geometric agreement metrics were determined from the comparisons between the two segmentation approaches. Feature selection was performed to optimize the training of a machine learning classification model to identify potential contouring errors. A public dataset with 339 cases was used to train and test the classifier. Four independent classifiers were trained using five‐fold cross validation, and the predictions from each classifier were ensembled using soft voting. The trained model was validated on a held‐out testing dataset. An additional independent clinical dataset with 60 cases was used to test the generalizability of the model. Model predictions were reviewed by an expert to confirm or reject the findings.

Results

The proposed machine learning multiple features (ML‐MF) approach outperformed traditional nonmachine‐learning‐based approaches that are based on only one or two geometric agreement metrics. The machine learning model achieved recall (precision) values of 0.842 (0.899), 0.762 (0.762), 0.727 (0.842), and 0.773 (0.773) for Brainstem, Parotid_L, Parotid_R, and mandible contours, respectively compared to 0.526 (0.909), 0.619 (0.765), 0.682 (0.882), 0.773 (0.568) for an approach based solely on Dice similarity coefficient values. In the external validation dataset, 66.7, 93.3, 94.1, and 58.8% of flagged cases were confirmed to have contouring errors by an expert for Brainstem, Parotid_L, Parotid_R, and mandible contours, respectively.

Conclusions

The proposed ML‐MF approach, which includes multiple geometric agreement metrics to flag manual contouring errors, demonstrated superior performance in comparison to traditional methods. This method is easy to implement in clinical practice and can help to reduce the significant time and labor costs associated with manual segmentation and review.
Information disclosure, consumer returns, and operational costs in omnichannel retailing
Authors: Liu Jie , Xiong Hui
Published: February 2023

In the online retailing, consumers are commonly uncertain about the product's quality and fitness. To resolve these uncertainties, many pure e‐tailers adopt various omnichannel strategies to provide tactile product information for consumers. We build a model to investigate a pure e‐tailer's decision on whether to adopt an omnichannel strategy. Our result indicates that when the cost for each physical store is sufficiently low, the e‐tailer always adopts the omnichannel strategy regardless of the product quality. Moreover, the low‐quality e‐tailer's willingness to adopt the omnichannel strategy is nonmonotonic with the fitness probability when the travel cost factor is high. In contrast, if the cost for each physical store is moderate, the e‐tailer adopts the omnichannel strategy if and only if the product quality is above a threshold. The quality threshold may increase with the fitness probability. Higher fitness probability means a lower return rate and fewer benefits brought by the omnichannel strategy. Thus, the threshold of the quality is increased to guarantee a sufficiently large price increase when choosing the omnichannel strategy. Furthermore, when the cost for each physical store is high, the e‐tailer with a high‐quality product would abandon the omnichannel strategy if the fitness probability is moderate. Finally, we consider the scenarios in which the e‐tailer can endogenously determine the number of physical stores or provide a partial refund policy.
Relationship between workplace bullying, spirituality, and job burnout in paediatric nurses: A cross‐sectional study
Authors: Fan Ying , Cao Mi , Zhou Yumei , Duan Peng , Xing Limin
Published: February 2023

Aims

To investigate the relationships and pathways between workplace bullying, workplace spirituality, and job burnout in Chinese paediatric nurses.

Design

A cross‐sectional descriptive survey was conducted with paediatric nurses from six tertiary hospitals in Hubei Province, China.

Methods

The study consisted of 402 paediatric nurses. The data were collected using a sociodemographic data questionnaire, Negative Acts Questionnaire‐Revised, Maslach Burnout Inventory‐General Survey and Workplace Spirituality Scale. The model was tested using path analysis techniques within structural equation modelling.

Results

Workplace bullying had positive and direct effects on the job burnout of paediatric nurses. Workplace spirituality partially mediated the relationship between workplace bullying and burnout.

Patient or Public Contribution

Workplace spirituality may reduce the incidence of work bullying and job burnout in paediatric nurses. Nursing managers need to consider and cultivate the workplace spirituality of paediatric nurses, with the aim of creating a healthy working environment and ensuring the stability of the nursing team.