bluuebunny/crossref_metadata_2025 huggingface dataset:
Cascade Oxidative C−H Annulation of Thiophenes: Heck‐Type Pathway Enables Concise Access to Thienoacenes
Authors: Chen Xingyu , Yang Yudong , Han Weiguo , Huang Quan , Huang Zhenmei , You Jingsong
Published: March 2021

The pursuit of efficient synthetic route to thienoacenes represents an appealing yet challenging task in the fields of both organic synthetic chemistry and organic functional materials. In this work, we disclose a rhodium‐catalyzed cascade C−H annulation of phenacyl phosphoniums with (benzo)thiophenes via a Heck‐type pathway to provide a new class of planar thienoacenes, which involves the formation of three Caryl‐Caryl bonds and one Caryl−O bond in a single operation. The neutral S,O‐heteroacenes exhibit superior stability and adopt a herringbone‐like packing mode with efficient π–π stacking in the crystals, suggesting their potential in organic semiconducting materials. This work first exemplifies the superiority of cascade oxidative C−H annulation involving a Heck‐type pathway in the development of concise access to heteroacenes.
Life history traits and conservation actions for the Maugean skate (Zearaja maugeana), an endangered species occupying an anthropogenically impacted estuary
Authors: Awruch Cynthia A. , Bell Justin D. , Semmens Jayson M. , Lyle Jeremy M.
Published: March 2021

The Maugean skate,Zearaja maugeana, is endemic to two isolated western Tasmanian (Australia) estuaries. The species' persistence in one of these estuaries (Bathurst Harbour) is uncertain, while the other estuary (Macquarie Harbour), potentially the remaining stronghold for the species, is an anthropogenically impacted system.

Key life‐history parameters were studied to inform conservation actions for this species. Reproductive information was obtained using non‐lethal methodologies, circulating concentrations of sex steroids and ultrasonography. Growth and age parameters were estimated based on vertebral sections from a small sample of individuals.

Females and males reached 870 and 760 mm total length, respectively. The species reached a maximum age of at least 10 years. Females and males attained 50% sexual maturity at 665 and 633 mm total length, respectively, probably maturing somewhere between four and six years of age. Females displayed an asynchronous, discontinuous reproductive cycle, being able to reproduce throughout the year, with a probable decline in reproductive activity during summer. No egg cases were observedin‐utero. Males produce sperm all year round, with a peak in testosterone production during spring–autumn.

Conservation strategies for Z. maugeanawill need to focus on reducing anthropogenic impacts on the environmental health, the primary impacts being altered river flows associated with the production of hydroelectricity and increased nutrient load associated with salmonid aquaculture. There is a need to better understand how reproductive success, egg survival and recruitment are affected by these environmental challenges if the future well‐being of this species is to be secured.
Association Between Gut Microbiota and Symptomatic Hand Osteoarthritis: Data From the Xiangya Osteoarthritis Study
Authors: Wei Jie , Zhang Chenhong , Zhang Yuqing , Zhang Weiya , Doherty Michael , Yang Tuo , Zhai Guangju , Obotiba Abasiama D. , Lyu Houchen , Zeng Chao , Lei Guanghua
Published: March 2021

Objective

Systemic inflammatory factors have been implicated in symptomatic hand osteoarthritis (OA). Gut microbiome dysbiosis promotes systemic inflammation. The aim of this study was to examine the association between the gut microbiome and the presence of symptomatic hand OA in a population‐based study.

Methods

Study participants were subjects of the Xiangya Osteoarthritis Study, a community‐based observational study conducted in the Hunan Province of China. Symptomatic hand OA was defined as the presence of both symptoms and radiographic OA in the same hand. The gut microbiome was analyzed using 16S ribosomal RNA gene sequencing in stool samples. We examined the relation of α‐diversity, β‐diversity, relative abundance of taxa, and potential bacterial functional pathways to symptomatic hand OA.

Results

A total of 1,388 participants (mean age 61.3 years, 57.4% women) were included in the study, of whom 72 had symptomatic hand OA (prevalence of symptomatic hand OA 5.2%). Beta‐diversity of the gut microbiome, but not α‐diversity, was significantly associated with the presence of symptomatic hand OA (P = 0.003). Higher relative abundance of the genera Bilophila and Desulfovibrio as well as lower relative abundance of the genus Roseburia was associated with symptomatic hand OA. Most functional pathways (i.e., those annotated in the KEGG Ortholog hierarchy) that were observed to be altered in participants with symptomatic hand OA belonged to the amino acid, carbohydrate, and lipid metabolic pathways.

Conclusion

This large, population‐based study provides the first evidence that alterations in the composition of the gut microbiome were observed among study participants who had symptomatic hand OA, and a low relative abundance of Roseburia but high relative abundance of Bilophila and Desulfovibrio at the genus level were associated with prevalent symptomatic hand OA. These findings may help investigators understand the role of the microbiome in the development of symptomatic hand OA and could contribute to potential translational opportunities.
Genetic and Epigenetic Interplay Within a COLGALT2 Enhancer Associated With Osteoarthritis
Authors: Kehayova Yulia S. , Watson Emily , Wilkinson J. Mark , Loughlin John , Rice Sarah J.
Published: March 2021

Objective

The osteoarthritis (OA)–associated single‐nucleotide polymorphism (SNP) rs11583641 is located in COLGALT2, encoding a posttranslational modifier of collagen. In cartilage, the SNP genotype correlates with DNA methylation in a putative enhancer. This study was undertaken to characterize the mechanistic relationship between rs11583641, the putative enhancer, and COLGALT2 expression using cartilage samples from human patients and a chondrocyte cell model.

Methods

Nucleic acids were extracted from articular cartilage samples obtained from patients with OA (n = 137). Samples were genotyped, and DNA methylation was quantified at 12 CpGs using pyrosequencing. The putative enhancer was deleted in Tc28a2 chondrocytes using clustered regularly interspaced short palindromic repeat/Cas9, and the impact on nearby gene expression was determined using real‐time quantitative polymerase chain reaction. Targeted modulation of the epigenome using catalytically dead Cas9 (dCas9) constructs fused to DNA methyltransferase 3a or ten–eleven translocase 1 allowed for the investigation of a causal relationship between DNA methylation and enhancer activity.

Results

The genotype at rs11583641 correlated with DNA methylation at 3 CpGs, and the presence of the OA risk allele, C, corresponded to reduced levels of methylation. Deletion of the enhancer resulted in a 2.7‐fold reduction in COLGALT2 expression. Targeted methylation and demethylation of the CpGs had antagonistic effects on COLGALT2 expression. An allelic imbalance in the expression of COLGALT2 was identified in the cartilage from patients with OA, with relative overexpression of the OA risk allele. Allelic expression ratios correlated with DNA methylation at 4 CpGs.

Conclusion

COLGALT2 is a target of OA genetic risk at this locus. The genotype at rs11583641 impacts DNA methylation in a gene enhancer, which, in turn, modulates COLGALT2 expression. COLGALT2 encodes an enzyme that initiates posttranslational glycosylation of collagens and is therefore a compelling OA susceptibility target.
When special populations intersect with drug–drug interactions: Application of physiologically‐based pharmacokinetic modeling in pregnant populations
Authors: Sychterz Caroline , Galetin Aleksandra , Taskar Kunal S.
Published: March 2021

Pregnancy results in significant physiological changes that vary across trimesters and into the postpartum period, and may result in altered disposition of endogenous substances and drug pharmacokinetics. Pregnancy represents a unique special population where physiologically‐based pharmacokinetic modeling (PBPK) is well suited to mechanistically explore pharmacokinetics and dosing paradigms without subjecting pregnant women or their fetuses to extensive clinical studies. A critical review of applications of pregnancy PBPK models (pPBPK) was conducted to understand its current status for prediction of drug exposure in pregnant populations and to identify areas of further expansion. Evaluation of existing pPBPK modeling efforts highlighted improved understanding of cytochrome P450 (CYP)‐mediated changes during pregnancy and identified knowledge gaps for non‐CYP enzymes and the physiological changes of the postpartum period. Examples of the application of pPBPK beyond simple dose regimen recommendations are limited, particularly for prediction of drug–drug interactions (DDI) or differences between genotypes for polymorphic drug metabolizing enzymes. A raltegravir pPBPK model implementing UGT1A1 induction during the second and third trimesters of pregnancy was developed in the current work and verified against clinical data. Subsequently, the model was used to explore UGT1A1‐related DDI risk with atazanavir and rifampicin along with the effect of enzyme genotype on raltegravir apparent clearance. Simulations of pregnancy‐related induction of UGT1A1 either exacerbated UGT1A1 induction by rifampicin or negated atazanavir UGT1A1 inhibition. This example illustrated the advantages of pPBPK modeling for mechanistic evaluation of complex interplays of pregnancy‐ and drug‐related effects in support of model‐informed approaches in drug development.
FAM84B acts as a tumor promoter in human glioma via affecting the Akt/GSK‐3β/β‐catenin pathway
Authors: Wang Minjuan , Li Chengliang , Shi Wei
Published: March 2021

Family with sequence similarity 84, member B (FAM84B) has recently emerged as an oncoprotein in multiple types of cancer. However, whether FAM84B modulates the progression of glioma has not been determined. The goals of this work were to assess the possible relationship between FAM84B and glioma. Our data revealed high FAM84B level in glioma specimens and exhibited that the overexpression of FAM84B was correlated with a low survival rate in glioma patients. Cellular functional assays showed that silencing of FAM84B prohibited the proliferation and invasion, and induced the apoptosis of glioma cells. Further results determined that the knockdown of FAM84B remarkably decreased the levels of phosphorylated Akt and glycogen synthase kinase (GSK)‐3β, and active β‐catenin. Inhibition of Akt abolished the FAM84B‐mediated promotion effects on Wnt/β‐catenin pathway. The subcutaneous xenograft assay confirmed that the silencing of FAM84B significantly prohibited the tumorigenicity of glioma cells in vivo. Collectively, the findings from this work demonstrate that the downregulation of FAM84B exhibits a cancer‐suppressive role in human glioma through the regulation of Akt/GSK‐3β/β‐catenin pathway.
Epithelial cell adhesion molecule promotes breast cancer resistance protein‐mediated multidrug resistance in breast cancer by inducing partial epithelial–mesenchymal transition
Authors: Shi Rui‐Zan , He Yi‐Fan , Wen Jie , Niu Ya‐Nan , Gao Yu , Liu Lin‐Hong , Zhang Xuan‐Ping , Wang Yan , Zhang Xiu‐Li , Zhang Hui‐Feng , Chen Min , Hu Xiao‐ling
Published: March 2021

Overexpression of breast cancer resistance protein (BCRP) plays a crucial role in the acquired multidrug resistance (MDR) in breast cancer. The elucidation of molecular events that confer BCRP‐mediated MDR is of major therapeutic importance in breast cancer. Epithelial cell adhesion molecule (EpCAM) has been implicated in tumor progression and drug resistance in various types of cancers, including breast cancer. However, the role of EpCAM in BCRP‐mediated MDR in breast cancer remains unknown. In the present study, we revealed that EpCAM expression was upregulated in BCRP‐overexpressing breast cancer MCF‐7/MX cells, and EpCAM knockdown using siRNA reduced BCRP expression and increased the sensitivity of MCF‐7/MX cells to mitoxantrone (MX). The epithelial–mesenchymal transition (EMT) promoted BCRP‐mediated MDR in breast cancer cells, and EpCAM knockdown partially suppressed EMT progression in MCF‐7/MX cells. In addition, Wnt/β‐catenin signaling was activated in MCF‐7/MX cells, and the inhibition of this signaling attenuated EpCAM and BCRP expression and partially reversed EMT. Together, this study illustrates that EpCAM upregulation by Wnt/β‐catenin signaling induces partial EMT to promote BCRP‐mediated MDR resistance in breast cancer cells. EpCAM may be a potential therapeutic target for overcoming BCRP‐mediated resistance in human breast cancer.
Trends in the utilization and reimbursement of coronary revascularization in the United States Medicare population from 2010 to 2018
Authors: Shah Aakash M. , Siddiqui Emaad , Cuenca Carlos , Drotar Persida , Okoh Alexis K. , Salemi Arash , Waxman Sergio , Sambol Justin
Published: March 2021

Objective

To determine utilization and reimbursement trends of coronary revascularization procedures in the US Medicare population from 2000 to 2018.

Background

US Medicare population is increasing, and coronary revascularization decreased in the 2000s.

Methods

This is a population‐based, cross sectional study of US Medicare beneficiaries from 2010 to 2018. The Centers for Medicare and Medicaid Services' database was queried for revascularization procedures using the coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) current procedural terminology (CPT) codes. Trends in Medicare enrollees, PCIs, CABGs, and physician reimbursements were analyzed.

Results

Total utilization and reimbursement decreased for both revascularization procedures. The national CABG and PCI utilization per enrollee has decreased by 40.7% (best fit line: b coefficient, 95% CI; −0.297, −0.358 to −0.235) and 26.4% (best fit line: −0.229, −0.373 to −0.0858), respectively. For CABG, annual Medicare payout per enrollee and physician compensation per procedure has decreased by 49.3% (best fit line: −0.250, −0.315 to −0.185) and 14.5% (best fit line: −11.54, −15.62 to −7.452), respectively, and for PCI, decreased by 53.3% (best fit line: −0.373, −0.560 to −0.186) and 36.6% (best fit line: −34.15, −49.35 to −18.95), respectively. Amongst the states, there was significant variability in procedure utilization, and CABG reimbursement rates but minimal variability in PCI reimbursement rates.

Conclusion

Even though the US population has aged, revascularization utilization and reimbursement continue to decline. Advancement in medical intervention strategies, particularly non‐surgical management, may account for these trends. Further understanding of these trends will allow health systems to tailor resources to the aging population.
Epidermal growth factor receptor inhibitor in advanced basal cell carcinoma
Authors: Amirabadi Amir , Alami Amirhosein , Ahanchian Hamid , Ariaee Nazila , Moazzen Nasrin
Published: March 2021

Cetuximab can be used for the treatment of advanced basal cell carcinoma, especially when the patient cannot tolerate routine chemotherapy. Future studies are needed to confirm it.
A Series of 2‐((1‐Phenyl‐1H‐imidazol‐5‐yl)methyl)‐1H‐indoles as Indoleamine 2,3‐Dioxygenase 1 (IDO1) Inhibitors
Authors: Zheng Yong , Stafford Paul M. , Stover Kurt R. , Mohan Darapaneni Chandra , Gupta Mayuri , Keske Eric C. , Schiavini Paolo , Villar Laura , Wu Fan , Kreft Alexander , Thomas Kiersten , Raaphorst Elana , Pasangulapati Jagadeesh P. , Alla Siva R. , Sharma Simmi , Mittapalli Ramana R. , Sagamanova Irina , Johnson Shea L. , Reed Mark A. , Weaver Donald F.
Published: March 2021

Indoleamine 2,3‐dioxygenase 1 (IDO1) is a promising therapeutic target in cancer immunotherapy and neurological disease. Thus, searching for highly active inhibitors for use in human cancers is now a focus of widespread research and development efforts. In this study, we report the structure‐based design of 2‐(5‐imidazolyl)indole derivatives, a series of novel IDO1 inhibitors which have been designed and synthesized based on our previous study using N1‐substituted 5‐indoleimidazoles. Among these, we have identified one with a strong IDO1 inhibitory activity (IC50=0.16 μM, EC50=0.3 μM). Structural‐activity relationship (SAR) and computational docking simulations suggest that a hydroxyl group favorably interacts with a proximal Ser167 residue in Pocket A, improving IDO1 inhibitory potency. The brain penetrance of potent compounds was estimated by calculation of the Blood Brain Barrier (BBB) Score and Brain Exposure Efficiency (BEE) Score. Many compounds had favorable scores and the two most promising compounds were advanced to a pharmacokinetic study which demonstrated that both compounds were brain penetrant. We have thus discovered a flexible scaffold for brain penetrant IDO1 inhibitors, exemplified by several potent, brain penetrant, agents. With this promising scaffold, we provide herein a basis for further development of brain penetrant IDO1 inhibitors.
Identification of Natural Products as Potential Pharmacological Chaperones for Protein Misfolding Diseases
Authors: Sharma Richa , Srivastava Tulika , Pandey Alka Raj , Mishra Tripti , Gupta Bhagyashri , Reddy Sabbu Sathish , Singh Suriya P. , Narender Tadigoppula , Tripathi Aradhya , Chandramouli Balasubramanian , Sashidhara Koneni V. , Priya Smriti , Kumar Niti
Published: March 2021

Defective protein folding and accumulation of misfolded proteins is associated with neurodegenerative, cardiovascular, secretory, and metabolic disorders. Efforts are being made to identify small‐molecule modulators or structural‐correctors for conformationally destabilized proteins implicated in various protein aggregation diseases. Using a metastable‐reporter‐based primary screen, we evaluated pharmacological chaperone activity of a diverse class of natural products. We found that a flavonoid glycoside (C‐10, chrysoeriol‐7‐O‐β‐D‐glucopyranoside) stabilizes metastable proteins, prevents its aggregation, and remodels the oligomers into protease‐sensitive species. Data was corroborated with additional secondary screen with disease‐specific pathogenic protein. In vitro and cell‐based experiments showed that C‐10 inhibits α‐synuclein aggregation which is implicated in synucleinopathies‐related neurodegeneration. C‐10 interferes in its structural transition into β‐sheeted fibrils and mitigates α‐synuclein aggregation‐associated cytotoxic effects. Computational modeling suggests that C‐10 binds to unique sites in α‐synuclein which may interfere in its aggregation amplification. These findings open an avenue for comprehensive SAR development for flavonoid glycosides as pharmacological chaperones for metastable and aggregation‐prone proteins implicated in protein conformational diseases.
Imaging Spontaneous Neuronal Activity with Voltage‐Sensitive Dyes
Authors: Raliski Benjamin K. , Kirk Molly J. , Miller Evan W.
Published: March 2021

Accurately mapping changes in cellular membrane potential across large groups of neurons is crucial for understanding the organization and maintenance of neural circuits. Measuring cellular voltage changes by optical means allows greater spatial resolution than traditional electrophysiology methods and is adaptable to high‐throughput imaging experiments. VoltageFluors, a class of voltage‐sensitive dyes, have recently been used to optically study the spontaneous activity of many neurons simultaneously in dissociated culture. VoltageFluors are particularly useful for experiments investigating differences in excitability and connectivity between neurons at different stages of development and in different disease models. The protocols in this article describe general procedures for preparing dissociated cultures, imaging spontaneous activity in dissociated cultures with VoltageFluors, and analyzing optical spontaneous activity data. © 2021 Wiley Periodicals LLC.

This article was corrected on 20 July 2022. See the end of the full text for details.

Basic Protocol 1: Preparation of dissociated rat hippocampal or cortical cultures

Alternate Protocol: Preparation of microisland dissociated cultures

Basic Protocol 2: Imaging of spontaneous activity in dissociated cultures using voltage‐sensitive dyes

Basic Protocol 3: Analysis of spontaneous activity imaging data
Corporate social responsibility antecedents and practices as a path to enhance organizational performance: The case of small and medium sized enterprises in an emerging economy country
Authors: Cheffi Walid , Malesios Chrisovalantis , Abdel‐Maksoud Ahmed , Abdennadher Sonia , Dey Prasanta
Published: March 2021

The impact of stakeholders' pressure and business uncertainties on the correlation between corporate social responsibility (CSR) and organizational performance within small and medium sized enterprises (SMEs) is under researched. This study aims to derive the correlation of CSR antecedents, CSR practices, stakeholders' pressures, business uncertainties, and organizational performance of SMEs in the UAE. The data was collected through a survey from 117 SMEs in the UAE, and analyzed using structural equation modeling. The study reveals that the level of importance SMEs attach to CSR antecedents influences positively the extent of SMEs involvement with CSR practices; and these, in turn, translate into significant performance outcomes for SMEs. Business uncertainties are proved to moderate both relationships (CSR antecedents‐CSR practices; and CSR practices‐SMEs performance); while stakeholders' pressure is found to have no moderating effect on CSR antecedent‐CSR practices relationship. The proposed framework could be adopted in any economy for enhancing performance through CSR.
Experimental validation of nine‐level switched‐capacitor inverter topology with high voltage gain
Authors: Mohamed Ali Jagabar Sathik , Siddique Marif Daula , Mekhilef Saad , Yang Yongheng , Siwakoti Yam , Blaabjerg Frede
Published: March 2021

This paper proposes a new switched‐capacitor nine‐level (9L) inverter with reduced switch count. In the proposed topology, floating capacitor (FC) is employed as a voltage booster, and it does not need any additional sensors to maintain the voltage across the FC. Due to additional FC, the number of dc sources and voltage stress on switches is reduced. Moreover, the proposed topology can be cascaded to achieve more voltage levels. Various parameters are considered in the comparison of the proposed topology with other recent switched‐capacitor topologies. Simulation and experimental results demonstrate the performance with different load and modulation index variations.
VEGF‐C/VEGFR‐3 axis protects against pressure‐overload induced cardiac dysfunction through regulation of lymphangiogenesis
Authors: Lin Qiu‐Yue , Zhang Yun‐Long , Bai Jie , Liu Jin‐Qiu , Li Hui‐Hua
Published: March 2021

Prolonged pressure overload triggers cardiac hypertrophy and frequently leads to heart failure (HF). Vascular endothelial growth factor‐C (VEGF‐C) and its receptor VEGFR‐3 are components of the central pathway for lymphatic vessel growth (also known as lymphangiogenesis), which has crucial functions in the maintenance of tissue fluid balance and myocardial function after ischemic injury. However, the roles of this pathway in the development of cardiac hypertrophy and dysfunction during pressure overload remain largely unknown. Eight‐ to 10‐week‐old male wild‐type (WT) mice, VEGFR‐3 knockdown (VEGFR‐3f/−) mice, and their WT littermates (VEGFR‐3f/f) were subjected to pressure overload induced by transverse aortic constriction (TAC) for 1–6 weeks. We found that cardiac lymphangiogenesis and the protein expression of VEGF‐C and VEGFR‐3 were upregulated in the early stage of cardiac hypertrophy but were markedly reduced in failing hearts. Moreover, TAC for 6 weeks significantly reduced cardiac lymphangiogenesis by inhibiting activation of VEGFR‐3‐mediated signals (AKT/ERK1/2, calcineurin A/NFATc1/FOXc2, and CX43), leading to increased cardiac edema, hypertrophy, fibrosis, apoptosis, inflammation, and dysfunction. These effects were further aggravated in VEGFR‐3f/− mice and were dose‐dependently attenuated by delivery of recombinant VEGF‐C156S in WT mice. VEGF‐C156s administration also reversed pre‐established cardiac dysfunction induced by sustained pressure overload. Thus, these results demonstrate, for the first time, that activation of the VEGF‐C‐VEGFR‐3 axis exerts a protective effect during the transition from cardiac hypertrophy to HF and highlight selective stimulation of cardiac lymphangiogenesis as a potential new therapeutic approach for hypertrophic heart diseases.
Accelerate equitable change by centering adult learners’ needs
Authors: Sutton Halley
Published: March 2021

Even before the COVID‐19 pandemic hit the world, 44 million adults in the United States were at risk of being left behind by the future of work. “Even before the pandemic, a lot of these adults were struggling, and they certainly weren't equipped to ride out this massive disruption – none of us were,” Melissa Leavitt, Director of Research at the Strada Institute of the Future of Work, said.
Time: The ever‐elusive resource of an academic administrator
Authors: Schwebel David C.
Published: March 2021

If you ask a university administrator what their most precious resource is, they may recite common answers like skilled personnel, quality facilities, or a stable budget. But upon reflection, another answer may emerge also: time.
Outcomes for adults with anorexia nervosa who do not respond early to outpatient treatment
Authors: Wade Tracey , Ambwani Suman , Cardi Valentina , Albano Gaia , Treasure Janet
Published: March 2021

Objective

To better understand those patients with anorexia nervosa who do not show early response to treatment and are likely to have poorer outcome.

Method

From an existing data set of 187 patients with anorexia nervosa across 22 eating disorder outpatient services in the United Kingdom, participants who had started treatment and had at least one body mass index (BMI) observation in the first 6 weeks of treatment were eligible for these secondary analyses (N = 65), a latent class analysis of BMI change over the first 6 weeks of treatment. Fifty‐six patients showed no early change in BMI. We used logistic regression to examine predictors of good outcome in the 40 participants who had 12‐month follow‐up data. Predictors included global EDE‐Q, negative affect (Depression, Anxiety, and Stress Scales) and functional impairment (Work and Social Adjustment Scale).

Results

Good outcome was achieved by 23% of patients and remission by 15%. Good outcome was predicted by less functional impairment at baseline.

Discussion

Further work that can identify sub‐groups of patients with anorexia nervosa who do not achieve good outcome after treatment will inform the development of targeted engagement approaches.
Fine‐scale oceanographic drivers of reef manta ray (Mobula alfredi) visitation patterns at a feeding aggregation site
Authors: Harris Joanna L. , Hosegood Phil , Robinson Edward , Embling Clare B. , Hilbourne Simon , Stevens Guy M. W.
Published: March 2021

Globally, reef manta rays (Mobula alfredi) are in decline and are particularly vulnerable to exploitation and disturbance at aggregation sites. Here, passive acoustic telemetry and a suite of advanced oceanographic technologies were used for the first time to investigate the fine‐scale (5‐min) influence of oceanographic drivers on the visitation patterns of 19 tagged M. alfredi to a feeding aggregation site at Egmont Atoll in the Chagos Archipelago. Boosted regression trees indicate that tag detection probability increased with the intrusion of cold‐water bores propagating up the atoll slope through the narrow lagoon inlet during flood tide, potentially transporting zooplankton from the thermocline. Tag detection probability also increased with warmer near‐surface temperature close to low tide, with near‐surface currents flowing offshore, and with high levels of backscatter (a proxy of zooplankton biomass). These combinations of processes support the proposition that zooplankton carried from the thermocline into the lagoon during the flood may be pumped back out through the narrow inlet during an ebb tide. These conditions provide temporally limited feeding opportunities for M. alfredi, which are tied on the tides. Results also provide some evidence of the presence of Langmuir Circulation, which transports and concentrates zooplankton, and may partly explain why M. alfredi occasionally remained at the feeding location for longer than that two hours. Identification of these correlations provides unique insight into the dynamic synthesis of fine‐scale oceanographic processes which are likely to influence the foraging ecology of M. alfredi at Egmont Atoll, and elsewhere throughout their range.
Hagenia from the early Miocene of Ethiopia: Evidence for possible niche evolution?
Authors: Grímsson Friðgeir , Ulrich Silvia , Coiro Mario , Graham Shirley A. , Jacobs Bonnie F. , Currano Ellen D. , Xafis Alexandros , Zetter Reinhard
Published: March 2021

Fossil pollen believed to be related to extant Hagenia abyssinica were discovered in the early Miocene (21.73 Ma) Mush Valley paleoflora, Ethiopia, Africa. Both the fossil and extant pollen grains of H. abyssinica were examined with combined light microscopy, scanning electron microscopy, and transmission electron microscopy to compare the pollen and establish their relationships. Based on this, the fossil pollen grains were attributed to Hagenia. The presence of Hagenia in the fossil assemblage raises the questions if its habitat has changed over time, and if the plants are/were wind pollinated. To shed light on these questions, the morphology of extant anthers was also studied, revealing specialized hairs inside the anthers, believed to aid in insect pollination. Pollen and anther morphology are discussed in relation to the age and origin of the genus within a molecular dated phylogenetic framework, the establishment of complex topography in East Africa, other evidence regarding pollination modes, and the palynological record. The evidence presented herein, and compiled from the literature, suggests that Hagenia was an insect‐pollinated lowland rainforest element during the early Miocene of the Mush Valley. The current Afromontane habitat and ambophilous (insect and wind) pollination must have evolved in post‐mid‐Miocene times.
Tree mortality in western U.S. forests forecasted using forest inventory and Random Forest classification
Authors: McNellis Brandon E. , Smith Alistair M. S. , Hudak Andrew T. , Strand Eva K.
Published: March 2021

Climate change is projected to significantly affect the vulnerability of forests across the western United States to wildfires, insects, disease, and droughts. Here, we provide recent mortality estimates for large trees for 53 species across 48 ecological sections using an analysis of 23,215 Forest Inventory plots and a Random Forest classification model. Models were also used to predict mortality in future FIA inventories under the RCP 4.5 emissions scenario. Model performance indicated species identity as the most important predictor of mortality under both current and future scenarios, with contributions from climate and soil variables. Our results show relatively high levels of recent mortality in the Middle and Southern Rocky Mountains driven by high mortality in Populus tremuloides, Pinus contorta, Pinus albicaulis, and Abies lasiocarpa. Low levels of mortality were observed in several species, with <1% annual mortality observed throughout all other sections. Future mortality was predicted to increase significantly for most species and correlated well with recent mortality at the species level, but not at the plot level. These results suggest that future attempts to model or predict widespread forest mortality would benefit from more research on vulnerable species and that significant mortality events in some species may not be important for dynamics across all systems.
Seasonal variation in habitat selection for a Neotropical migratory songbird using high‐resolution GPS tracking
Authors: Stanley Calandra Q. , Dudash Michele R. , Ryder Thomas B. , Shriver W. Gregory , Serno Kimberly , Adalsteinsson Solny , Marra Peter P.
Published: March 2021

Deciphering how environmental heterogeneity affects population dynamics in migratory species is complicated by the redistribution of individuals in time and space across the annual cycle. Approaches that tackle this problem require information about how migratory species respond to ecological factors across time and space, and how they are linked across migratory periods. Using high spatial resolution (10 m) GPS tracking of individual male songbirds, we quantified for the first time (1) local‐ and landscape‐scale habitat selection across the annual cycle and (2) patterns indicative of regional habitat selection for individuals within five populations of wood thrush (Hylocichla mustelina) throughout their breeding range. Wood thrush exhibited seasonal variation in local‐ and landscape‐scale habitat selection. Within stationary periods, wood thrush occupied forested habitats and proximity to forest edge was an important predictor of habitat selection at the local scale. In contrast, during migratory periods wood thrush exhibited greater behavioral flexibility indicative of a more generalist approach to habitat selection. Landscape habitat selection was only identified during the breeding season (average patch size) and could be a response to the extensive forest fragmentation in the North American breeding grounds. We also identified individual population distribution patterns indicative of regional habitat selection during fall migration and winter period, but not spring migration. Seasonal changes in habitat selection at multiple spatial scales suggest the factors driving habitat selection patterns are aligned with life‐history stage and may be dependent on regional differences in landscape composition. These results highlight the importance of a full annual cycle approach to ecological studies that address how migratory species respond to spatial and temporal environmental heterogeneity.
The social learning potential of participatory water valuation workshops: A case study in Tasmania, Australia
Authors: Nikkels Melle J. , Leith Peat , Kumar Saideepa , Mendham Neville , Dewulf Art
Published: March 2021

Participatory water valuation workshops are useful for their valuation outcomes, but can they also foster social learning? Social learning involves changes in understanding through social interactions between actors, which go beyond the individual to become situated within wider social units. Participatory water valuation workshops involve dialoguing about knowledge, perspectives, and preferences, which may be conducive to social learning. In this paper, we assess the social learning potential of a participatory valuation workshop, based on a case study in Tasmania, where farmers, water managers, and a policy maker shared their personal perspectives on the past, current and future values of irrigation water. To assess the social learning potential of a single participatory valuation workshop, we analyzed drivers—that is, factors positively influencing social learning—and outcomes—that is, indications that social learning occurred. Data were collected through an exit survey, in‐workshop reflections and semistructured interviews following 3 weeks and 6 months after the actual workshop. The results indicate that the workshop provided the drivers for social learning to occur. In addition, participants indicated to have learned from and with others, and that the workshop provided improved and extended networks. According to the participants, the workshop led to a shared concern about increasing prices for water licences and induced substantive outcomes related to the use, management, and governance of irrigation water. We conclude that participatory valuation workshops, such as the one analyzed here, can foster social learning.
Expanding frontiers in telehealth: Video assisted at‐home application of capsaicin 8% patch
Authors: Shaparin Naum , Nair Singh , Vydyanathan Amaresh , Hascalovici Jacob R.
Published: March 2021

In recent years, the delivery of health services has undergone a major paradigm shift towards expanded outpatient services and widespread use of telemedicine. Post‐herpetic neuralgia (PHN) is a treatment recalcitrant neuropathic pain condition referring to pain persisting more than three months from the initial onset of an acute herpes zoster. QUTENZA® (capsaicin 8% patch) is a single 1‐hr localized treatment for PHN and can provide several months of pain relief per application. However, patient access to capsaicin 8% patch is limited due to sensitive handling protocols that require the patch application to occur under physicians or healthcare professionals under the close supervision of a physician. Herein, we describe a successful treatment of PHN at‐home, using capsaicin 8% patch, performed under full supervision and instruction from a physician using video telehealth services.

Significance

This is a case report of the successful treatment of post‐herpetic neuralgia at‐home using Capsaicin 8% patch. The procedure was performed under full supervision and instruction from a physician using video telehealth services. Not only did the patient tolerate the procedure and have significant efficacy, she voiced preference to repeat treatment in this manner versus going back to the office.
Sublethal, Behavioral, and Developmental Effects of the Neonicotinoid Pesticide Imidacloprid on Larval Wood Frogs (Rana sylvatica)
Authors: Sweeney Megan R. , Thompson Cassandra M. , Popescu Viorel D.
Published: March 2021

Imidacloprid, a neonicotinoid pesticide, is used to prevent the spread of the hemlock woolly adelgid, currently affecting Eastern Hemlock trees across North America. When the pesticide is sprayed directly onto soil around infested trees (soil drenching), it can run off into aquatic systems, with potential negative effects on biota. Simultaneously, climate change may lead to faster pool drying, which acts as an additional stressor for sensitive species such as amphibians. We evaluated the sublethal effects of imidacloprid (10 ppb), and interaction with shorter hydroperiods on the larval behavior, growth, and survival of a model organism, the wood frog (Rana sylvatica). We performed 3 behavioral experiments evaluating swimming speed, time spent swimming, and distance the larvae swam. We found that larvae raised in 10 ppb imidacloprid or shorter hydroperiod did not differ in their swimming time, distance, and speed from nonexposed larvae. Naïve larvae exposed for 20 min to 10- to 500-ppb concentrations also showed similar performance to nonexposed larvae. However, when we applied a stimulus halfway through each experiment, we found that larvae exposed to 10 ppb imidacloprid (short and long term) swam shorter distances and spent less time swimming, suggesting that imidacloprid exposure may slow reaction time, potentially increasing the risk of predation. To minimize impacts on pool-breeding amphibians, imidacloprid application to combat the invasive hemlock woolly adelgid should use trunk injection and avoid soil drenching. Environ Toxicol Chem 2021;40:1838–1847. © 2021 SETAC
The treatment strategy of patients with positive margins after cervical cold knife conization—A 7‐year retrospective study in China
Authors: Fu Kun , Lei Ming , Yang Wen‐Qing , Wu Li‐Sha , Shi Jing‐Cheng , Zhang Yu
Published: March 2021

Objective

To explore treatment strategies for patients with positive margins after cervical cold knife conization (CKC) by estimating the risk of residual or recurrent CIN2 or worse (CIN2+).

Methods

A retrospective study included 569 patients receiving CKC for CIN3 in Xiangya Hospital from January 2013 to December 2017. Demographic characteristics and test results were obtained before CKC, after CKC, at 6, 12, and 24 months, then annually thereafter. The primary end point was residual/recurrent CIN2+ post‐CKC.

Results

Fourteen (2.46%) patients had residual/recurrent CIN2+ with a median time of occurrence at 12 months post‐CKC. Taking the average age and hrHPV viral load tested by Hybrid Capture 2 (HC2) as thresholds, the risk of residual/recurrent CIN2+ was higher in women aged over 40 years or with a baseline HC2 of 300 or more for the ratio of relative light units to positive cut‐off values. Patients with positive margins were at higher risk of residual/recurrent CIN2+ (hazard ratio 3.66, 95% confidence interval 1.25–10.71), especially when endocervix was involved. A total of 536 (94.20%) patients received HPV testing within 6 months after CKC. Patients with both positive HPV testing results and positive margins were at the highest risk of residual/recurrent CIN2+.

Conclusion

Patients with positive endocervical margins are at high risk for residual/recurrent CIN2+, independent of the severity of margins. HPV testing within 6 months after CKC may be a feasible triage strategy for these patients.
Spectrochemical determination of effects on rat liver of binary exposure to benzo[a]pyrene and 2,2′,4,4′‐tetrabromodiphenyl ether
Authors: Liu Shu‐Zhen , Luo You‐Hong , Morais Camilo L. M. , Ma Xiao‐Jun , Yang Li‐Jun , Tan De‐Chan , Li Jin‐Bo , Liao Bao‐Yi , Wei Yuan‐Feng , Martin Francis L. , Pang Wei‐Yi
Published: March 2021

Benzo[a]pyrene (B[a]P) and polybrominated diphenyl ethers (PBDEs) are persistent environmental contaminants. The effects in organisms of exposures to binary mixtures of such contaminants remain obscure. Attenuated total reflection Fourier‐transform infrared (ATR‐FTIR) spectroscopy is a label‐free, non‐destructive analytical technique allowing spectrochemical analysis of macromolecular components, and alterations thereof, within tissue samples. Herein, we employed ATR‐FTIR spectroscopy to identify biomolecular changes in rat liver post‐exposure to B[a]P and BDE‐47 (2,2′,4,4′‐tetrabromodiphenyl ether) congener mixtures. Our results demonstrate that significant separation occurs between spectra of tissue samples derived from control versus exposure categories (accuracy = 87%; sensitivity = 95%; specificity = 79%). Additionally, there is significant spectral separation between exposed categories (accuracy = 91%; sensitivity = 98%; specificity = 90%). Segregation between control and all exposure categories were primarily associated with wavenumbers ranging from 1600 to 1700 cm−1. B[a]P and BDE‐47 alone, or in combination, induces liver damage in female rats. However, it is suggested that binary exposure apparently attenuates the toxic effects in rat liver of the individual contaminants. This is supported by morphological observations of liver tissue architecture on hematoxylin and eosin (H&E)‐stained liver sections. Such observations highlight the difficulties in predicting the endpoint effects in target tissues of exposures to mixtures of environmental contaminants.
An innovative use of electrochemically modified three‐dimensional carbon felt for a rapid recovery of gold from diluted chloride solution
Authors: Kanagaratnam Jeeveni , Suah Faiz Bukhari Mohd
Published: March 2021

BACKGROUND

This study presents the novel use of modified Shipley‐activated carbon felt in an electrogenerative process via flow‐through batch recycle cell to recover gold, Au(III), from chloride solutions.

RESULTS

The recovery of Au(III) was conducted in a batch recycle cell equipped with three‐dimensional activated carbon felt as a cathode and zinc as an anode. Several initial Au(III) concentrations (50, 100, 250, and 500 mg L−1) and different types of cathode materials (carbon felt and reticulated vitreous carbon) were used to evaluate the cell performance. Both the electrodes were at the same size (2.0 cm × 5.3 cm × 0.3 cm) and volume (3.18cm3). At optimum conditions, total Au(III) recovery was achieved with the use of activated carbon felt at a concentration of 500 mg L−1 within 30 min of operation with a flow rate of 50 mL min−1. This was achieved at a fractional conversion of 1.00, where all the 2894 mol of Au were fully deposited at the cathode. This can be ascribed to the massive surface area and high porosity of carbon felt. Carbon felt has a specific surface area of 1229 cm2g−1 and a porosity of 94.81%. The morphological and compositional studies of the electrodeposited Au(III) onto activated carbon felt cathode material were also carried out.

CONCLUSION

It is confirmed that Au(III) has been successfully deposited by cathodic reduction of Au(III) ions. © 2021 Society of Chemical Industry (SCI).
Wanted: A vocabulary for talking about involuntary behaviors associated with Lesch‐Nyhan disease
Authors: Robey Kenneth L. , Balboni Daniel C.
Published: March 2021

Lesch‐Nyhan disease (LND) is a rare genetic disorder with an unusual behavioral phenotype that includes severe and involuntary self‐injury requiring the near constant use of protective devices and, for some individuals, dental extraction. Often, the person with LND also engages in emotional self‐injury in the form of both self‐sabotage and behaviors directed toward others that will have a negative social consequence. When these self‐destructive behaviors present themselves, it is sometimes challenging for caregivers, professionals, or other observers to fully recognize their lack of volition. It is an even greater challenge to accurately and convincingly convey their involuntary nature to medical students, colleagues, school staff, or even family members who might be unfamiliar with the disorder. It is difficult to find words to clearly and adequately convey the essence of behaviors like those that we find in LND without, in some way, implying intent.
Ultrastructure of rhizoids in the marine bryozoan Dendrobeania fruticosa (Gymnolaemata: Cheilostomata)
Authors: Shunatova Natalia , Denisova Sofia , Shchenkov Sergei
Published: March 2021

Bryozoans form colonies of iterated modules, termed zooids, and display varying degrees of polymorphism. Polymorphic colonies comprise autozooids (or feeding zooids) and heteromorphic zooids, among which the most common types are avicularia and kenozooids. Kenozooids differ in shape, size, and presumed function. Among this diversity, there are rhizoids, which serve to attach colonies to the substrate or to lift them above it. To date, only general data on anatomy of kenozooids at light microscopy level are available. Here, we present the first description of the ultrastructure of the holdfast‐like rhizoids of the cheilostome bryozoan Dendrobeania fruticosa. The rhizoid wall is composed of a single‐layered epidermis, which produces the ectocyst. The voluminous cavity is acoelomate: it has no special cellular lining, nor any signs of an extracellular matrix toward the epidermis. It is traversed by delicate branching funicular strands that originate from the pore plate. The only cells in contact with the epidermis are the cells of the funicular system and the storage cells. The pore plate between the rhizoid and autozooid includes a variable number of communication pores. Each pore is plugged with a rosette complex, which includes a cincture cell and four special cells extending through the pore. The limiting cells are absent, and the special cells are in direct contact with the funicular strands. Cell contacts between special cells are absent; moreover, there are spaces between their proximal lobes filled with a heterogeneous matrix similar to that in the lumen of the funicular strands. Such matrix is also found outside of the extracellular matrix surrounding the special cells. These findings allow us to suggest that nutrient transport most likely occurs between, rather than through, the special cells. However, further studies are needed to understand how the rosette complex functions.