bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of ruthenium (II) complexes with furan‐substituted ligands as possible antibacterial agents against Staphylococcus aureus
Authors: Liao Xiangwen , Wang Jing , Jiang Guijuan , Lingyu Mao , Jiang Guangbin , Wang Jintao , Huang Bin
Published: August 2021

The growing burden of antibiotic resistance worldwide calls for developing new classes of antimicrobial strategy. Recently years, the use of adjuvants that rescue antibiotics identified as a promising strategy for overcoming bacterial resistance. In this study, three ruthenium complexes functionalized with furan‐substituted ligands([Ru(phen)2(CAPIP)](ClO4)2 (Ru(Ⅱ)‐1), [Ru(dmp)2(CAPIP)](ClO4)2 (Ru(Ⅱ)‐2) and [Ru(dmb)2(CAPIP)](ClO4)2 (Ru(Ⅱ)‐3) (dmb=4,4′‐dimethyl‐2,2′‐bipyridine, phen=1,10‐phenanthroline, dmp=2,9‐dimethyl‐1,10‐phenanthroline, CAPIP=(E)‐2‐ (2‐(furan‐2‐yl)vinyl)‐1H‐imidazo[4,5‐f][1,10]phenanthroline)) were designed and synthesized. The antimicrobial activities of all compounds against S. aureus were assessed by growth inhibition assays. The MIC values of three complexes range from 0.015 to 0.050 mg/ml. Subsequently, the Ru(II)‐2 complexes which exhibited strongest antibacterial activity were further tested against bacteria biofilms formation and toxin secretion. In addition, aimed to test whether ruthenium complexes have potential value as antimicrobial adjuvants, the synergism between Ru(Ⅱ)‐2 and some antibiotics against S. aureus were examined through checkerboard method. Interestingly, Ru(Ⅱ)‐2 could not only effectively inhibit biofilms formation of S. aureus and inhibit the hemolysin toxin secretion, but also selectivity show synergism with two common antibiotics. More importantly, mouse infection study also verified Ru(Ⅱ)‐2 were highly effective against S. aureus in vivo.
O‐prenylated carbostyrils as a novel class of 15‐lipoxygenase inhibitors: Synthesis, characterization, and inhibitory assessment
Authors: Alavi Seyed Jamal , Zebarjadi Amir , Bafghi Mahdi Hosseini , Orafai Hossein , Sadeghian Hamid
Published: August 2021

Catalyzed peroxidation of unsaturated lipid in animals and plants intimately is linked to the activity of 15‐Lipoxygenase enzymes. Lipoxygenases (LOXs) are well known to play an important role in many acute and chronic syndromes such as inflammation, asthma, cancer, and allergy. In this study, a series of mono prenyloxycarbostyrils were synthesized and evaluated as potential inhibitors of soybean 15‐Lipoxygenase (SLO) and their inhibitory potencies were compared to mono prenyloxycoumarins which had been reported in the previous works. The synthetic compounds inhibit lipoxygenase enzyme by competitive mechanism like the prenyloxy coumarins. The results showed that position and length of the prenyl moiety play the important role in lipoxygenase inhibitory activity. Among all of the synthetic compounds (coumarin and carbostyril derivatives), 5‐farnesyloxycoumarin and 8‐farnesyloxycarbostyril demonstrated the best inhibitory activity by IC50 values of 1.1 µM and 0.53 µM, respectively.
Green synthesis and characterization of Solanum xanthocarpum capped silver nanoparticles and its antimicrobial effect on multidrug‐resistant bacterial (MDR) isolates
Authors: Pungle Rohini , Nile Shivraj Hariram , Kharat Arun S.
Published: August 2021

Plant extracts and their bioactive compounds are considered as the promising options for green synthesis of nanoparticles instead expensive and hazardous materials. Here, Solanum xanthocarpum fruit was used for synthesis of silver nanoparticles (AgNP). The synthesized AgNPs were characterized by using chromatographic and spectroscopic analytical methods. AgNPs were confirmed by UV‐visible absorbance at 420–470 nm. TEM analysis showed AgNP with 22.45 nm average size. X‐ray diffraction studies revealed the crystalline and face central cubic nature of AgNPs. FTIR analysis revealed functional group present over AgNPs. The aminodiphenyl acetic acid, clomipramine, and fonisopril from fruit extracts were found to be major capping agents on AgNPs as a result of analysis by HRLC‐MS. All clinical isolates showed resistance for ampicilline, amoxyclav, niladixic acid, and sulphafurazole, suggesting multidrug resistance. The results showed that all isolates were sensitive to AgNPs synthesized fruit extracts. On the contrary, all isolates were resistant to whole S. xanthocarpum fruit extracts alone. The antimicrobial activity of AgNP was explored against multidrug‐resistant (MDR) Gram‐negative clinical isolates including Escherichia coli, Shigella spp., Aeronomonas spp. and Pseudomonas spp. MIC values ranged between 1.25 mg/ml and 2.5 mg/ml at 8 McFarland's standards. Minimum bactericidal concentration was found to be in between 2.5 mg/ml to 5 mg/ml. Nanoparticles synthesized from fruit extract of S. xanthocarpum containing aminodiphenyl acetic acid, clomipramine, and fonisopril metabolites exhibit promising antimicrobial activity against MDR Gram‐negative clinical isolates.
A molecular phylogeny of Thuridilla Bergh, 1872 sea slugs (Gastropoda, Sacoglossa) reveals a case of flamboyant and cryptic radiation in the marine realm
Authors: Martín‐Hervás María del Rosario , Carmona Leila , Malaquias Manuel António E. , Krug Patrick J. , Gosliner Terrence M. , Cervera Juan Lucas
Published: August 2021

The genus Thuridilla Bergh, 1872 comprises mostly tropical sap‐sucking sea slugs species with flamboyantly coloured forms. However, the potential for cryptic or pseudocryptic species masked by convergent or polymorphic colour patterns has not been tested using molecular characters. In this study, we sampled 20 of the 23 recognized worldwide species and performed the most comprehensive molecular phylogenetic analysis of the genus to date using a multi‐locus approach combining two mitochondrial (cytochrome c oxidase subunit I, 16S rRNA) and two nuclear (Histone H3, 28S rRNA) genes using maximum likelihood, maximum‐parsimony and Bayesian criteria. Three molecular species delimitation methods (ABGD, GMYC, bPTP) and the morphology of radular teeth were additionally used to aid in species delimitation. Our analyses supported 35 species within Thuridilla, of which more than one‐third (13) are part of a single radiation here named the Thuridilla gracilis (Risbec, 1928) species‐complex. This complex includes T. gracilis, T. splendens (Baba, 1949), T. bayeri (Er. Marcus, 1965), and T. ratna (Er. Marcus, 1965), plus nine additional undescribed species. All 13 species are distinguishable by radular characters, external morphology and their DNA. The detection of this radiation led diversity of Thuridilla to be underestimated by about 25% and provides a new comparative system for studying the role of colour patterns in marine diversification.
Frequency of persistent obesity 5 years after first time diagnosis of status asthmaticus
Authors: Krawiec Conrad , Fang Xinying , Zhou Shouhao , Williams Duane , Thomas Neal J.
Published: August 2021

Background/Objectives

When a severe asthma exacerbation occurs in an obese pediatric patient, it is unknown if this body type persists in future encounters. Persistent obesity can lead to future asthma exacerbations. The main study objective is to evaluate the persistence of a BMI percentile ≥85th in children 5 years after the first reported diagnosis of status asthmaticus. We hypothesized that a hospital admission for status asthmaticus was associated with persistence of a BMI percentile ≥85th.

Methods

This was a long‐term retrospective observational cohort study utilizing TriNetX ® electronic health record (EHR) data. We included subjects aged 2 to 18 years of age with a diagnosis of status asthmaticus. Study population was divided into two groups based on their admission body mass index percentile: (underweight/healthy weight [<85th percentile] and overweight/obese [≥85th percentile]) and evaluated for the following outcomes: age, race, ethnicity, diagnostic codes, and BMI percentiles (initially and 5 years after diagnosis of status asthmaticus).

Results

A total of 129 subjects (n%) (76 [58.9%] underweight/healthy weight and 53 [41.1%] overweight/obese) were included. Children that were initially overweight/obese with status asthmaticus had significantly increased odds of continuing to be overweight/obese 5 years after diagnosis compared to children who were underweight/healthy weight at baseline (OR = 7.50 [95% confidence interval, 3.20–17.60; p < 0.001]).

Conclusions

Overweight/obese asthmatic children are at risk of continuing to be obese several years after being diagnosed with status asthmaticus. This study reinforces the notion that when an asthmatic obese child presents with status asthmaticus, a thorough evaluation of nutrition, physical activity, and asthma control should be considered to reduce the risk of persistent obesity and possibly future asthma exacerbations.
“Real‐world” first‐episode psychosis care in Massachusetts: Lessons learned from a pilot implementation of harmonized data collection
Authors: Kline Emily R. , Johnson Kelsey A. , Szmulewicz Alejandro , Davis Beshaun J. , Sanders Aliyah S. , Friedman‐Yakoobian Michelle , Ongur Dost , Stepansky Michael , Williamson Alyssa N. , Guyer Margaret , Keshavan Matcheri
Published: August 2021

Aim

Increasing evidence points to the value of coordinated specialty care (CSC) for early intervention in psychotic disorders. This report characterizes clinical and socio‐demographic features of patients at CSC programs in Massachusetts (MA), assessed by a standardized battery incorporated into “real‐world” clinical care.

Methods

The MA psychosis network for early treatment developed a pilot battery to coordinate assessments across six CSC clinics. Programs reported baseline, 6‐month, and 12‐month data from a sample of 287 patients with intake dates ranging from April 2015 to December 2020.

Results

Patients showed improvements in functioning, emergency service use and several symptom domains at 6 and 12 months. Missing data proved to be a limitation.

Conclusions

Patients improved on several meaningful domains within the first year of CSC treatment. Future implementation efforts in cross‐program data collection should consider strategies to circumvent limitations related to heterogeneity between clinics, patient discharge and clinics' capacity for data collection.
Immune‐related adverse events in cancer patients being treated with immune checkpoint inhibitors
Authors: Byrne Margaret M. , Lucas Mathew , Pai Lori , Breeze Janis , Parsons Susan K.
Published: August 2021

Introduction

With the increased use of immune checkpoint inhibitors (ICI), it is essential to improve our understanding of immune‐related adverse events (irAE). To date, most studies describing irAE have been performed in clinical trial populations, which may not be an accurate description of irAE in real‐world populations. Also, identification of patients at increased risk of irAE is needed as early recognition may improve irAE outcomes.

Methods

We performed a retrospective analysis of patients who received an ICI between January 2014 and October 2018 at a single institution (Tufts Medical Center). Each patient was followed for up to 12 months for the outcome of a physician‐reported irAE. Kaplan‐Meier curves were created for the time to development and resolution of initial irAE. A Cox proportional hazards model was created to evaluate whether the following variables were independent predictors of an initial irAE: age ≥65 years, female sex, non‐Caucasian race, radiation in previous 6 months, current smoking status, melanoma, and combination ICI (ipilimumab and nivolumab).

Results

Of 131 patients followed, 57 patients (43.5%) developed at least one irAE at a median of 250 days (95% confidence interval (CI) 132 days‐not estimable). The most common irAE included dermatitis, thyroid dysfunction, and pneumonitis. Nearly two‐thirds of patients with an irAE had ICI therapy withdrawn, and nearly 60% had immunosuppression initiated. In multivariable analysis, we found a significant association between irAE development and age ≥65 years hazard ratio (HR) 1.80, 95% CI (1.03‐3.14) and current smoking status (HR 2.26, 95% CI 1.06‐4.82).

Discussion

We detected a high rate of irAE and that irAE and subsequent management can be clinically burdensome in this patient population. While further studies are needed to validate these findings, this study provides insights into the magnitude, time course, management of, and possible predictors of irAE in a real‐world setting.
Aberrant hippocampal mossy fibers in temporal lobe epilepsy target excitatory and inhibitory neurons
Authors: Puhahn‐Schmeiser Barbara , Leicht Kathrin , Gessler Florian , Freiman Thomas M.
Published: August 2021

Objective

The pathoanatomical correlate of temporal lobe epilepsy is hippocampal sclerosis, characterized by selective neuronal death of mossy cells in the hilus and of pyramidal cells in cornu ammonis 1. Although granule cells survive, they lose mossy cells as a target and redirect their axons (mossy fibers) backward into the molecular cell layer. It has been assumed that this process results in excitatory circuits. We therefore examined whether sprouted mossy fibers form synaptic connection not only with excitatory granule cells but also with inhibitory interneurons, such as basket cells.

Methods

Resected hippocampal specimens of patients with hippocampal sclerosis were compared to controls of patients with extrahippocampal lesions with only mild sclerosis. Mossy fibers were traced with Neurobiotin or labeled against synaptoporin; inhibitory interneurons were labeled against parvalbumin. Synapses were examined with electron microscopy, labeled with γ‐aminobutyric acid immunogold.

Results

Sprouted mossy fibers of epileptic hippocampi innervate not only excitatory granule cells but also inhibitory parvalbuminergic interneurons. Despite neuronal death in hippocampal sclerosis, the axonal plexus of inhibitory parvalbuminergic interneurons surrounding the granule cells is preserved. Connections of sprouted mossy fibers and inhibitory axon terminals were quantified, showing that the number of inhibitory axon terminals significantly exceeds the number of sprouted excitatory mossy fiber terminals (.03 boutons/µm vs. .11 boutons/µm; p < .001).

Significance

Although no definite conclusions regarding the function of our findings may be derived from this anatomical study, the observed aberrant connectivity might lead to an increased inhibition and synchronization of granule cells, because the preserved inhibitory interneurons show an additional innervation through sprouted mossy fibers. This might result in the instability of a previously balanced network.
Vitamin D3 potentiates the nephroprotective effects of vildagliptin–metformin combination in a rat model of metabolic syndrome
Authors: Wahba Nehal S. , Abdel‐Ghany Rasha H. , Ghareib Salah A. , Abdel‐Aal Mohamed , Alsemeh Amira E. , Sabry Dina
Published: August 2021

The current study was conducted to investigate the nephroprotective effects of vildagliptin–metformin combination in an experimental model of fructose/salt‐induced metabolic syndrome (MetS). A major aim was to evaluate the potential capacity of vitamin D3 to potentiate the pleiotropic nephroprotective effects of vildagliptin–metformin combination. MetS was induced in adult male Wistar rats by adding fructose (10%) to everyday drinking water and salt (3%) to the diet for 6 weeks. Along with the same concentrations of fructose/salt feeding, MetS rats were then treated orally with either vildagliptin (10 mg/kg/day)–metformin (200 mg/kg/day) combination, vitamin D3 (10 μg/kg/day), or the triple therapy for a further 6 weeks. The incidence of MetS was confirmed 6 weeks after fructose/salt consumption, when the rats exhibited significant weight gain, dyslipidemia, hyperuricemia, insulin resistance, hyperinsulinemia, and impaired glucose tolerance. At the end of the 12‐week experimental period, MetS rats displayed significantly deteriorated renal function, enhanced intrarenal oxidative stress and inflammation together with exaggerated renal histopathological damages and interstitial fibrosis. The study has corroborated antioxidant, anti‐inflammatory, and antifibrotic effects of vildagliptin–metformin combination, vitamin D3, and the triple collaborative therapy, conferring renoprotection in the setting of MetS. Due attention has been paid to the crucial role of dipeptidyl peptidase‐4 inhibition and sirtuin‐1/5′ adenosine monophosphate‐activated protein kinase activation as novel therapeutic targets to optimize renoprotection. The apparent potentiating effect, evoked upon coadministration of vitamin D3 with vildagliptin–metformin combination, may provide a cornerstone for further clinical investigations.
Junctional complexes in epithelial cells: sentinels for extracellular insults and intracellular homeostasis
Authors: Fu Rong , Jiang Xiaowan , Li Gang , Zhu Yi , Zhang Huimin
Published: August 2021

The cell‐cell and cell‐ECM junctions within the epithelial tissues are crucial anchoring structures that provide architectural stability, mechanical resistance, and permeability control. Their indispensable role as signaling hubs orchestrating cell shape‐related changes such as proliferation, differentiation, migration, and apoptosis has also been well recognized. However, growing amount of evidence now suggests that the multitasking nature of epithelial junctions extends well beyond anchorage‐dependent or cell shape change‐related biological processes. In this review, we discuss the emerging roles of junctional complexes in regulating innate immune defense, stress resistance, and intracellular proteostasis of the epithelial cells, with emphasis on the upstream regulation of epithelial junctions on various aspects of the epithelial barrier.
Temperature and spatial connectivity drive patterns in freshwater macroinvertebrate diversity across the Arctic
Authors: Lento Jennifer , Culp Joseph M. , Levenstein Brianna , Aroviita Jukka , Baturina Maria A. , Bogan Daniel , Brittain John E. , Chin Krista , Christoffersen Kirsten S. , Docherty Catherine , Friberg Nikolai , Ingimarsson Finnur , Jacobsen Dean , Lau Danny Chun Pong , Loskutova Olga A. , Milner Alexander , Mykrä Heikki , Novichkova Anna A. , Ólafsson Jón S. , Schartau Ann Kristin , Shaftel Rebecca , Goedkoop Willem
Published: August 2021

Warming in the Arctic is predicted to change freshwater biodiversity through loss of unique taxa and northward range expansion of lower latitude taxa. Detecting such changes requires establishing circumpolar baselines for diversity, and understanding the primary drivers of diversity.

We examined benthic macroinvertebrate diversity using a circumpolar dataset of >1,500 Arctic lake and river sites. Rarefied α diversity within catchments was assessed along latitude and temperature gradients. Community composition was assessed through region‐scale analysis of β diversity and its components (nestedness and turnover), and analysis of biotic–abiotic relationships.

Rarefied α diversity of lakes and rivers declined with increasing latitude, although more strongly across mainland regions than islands. Diversity was strongly related to air temperature, with the lowest diversity in the coldest catchments. Regional dissimilarity was highest when mainland regions were compared with islands, suggesting that connectivity limitations led to the strongest dissimilarity. High contributions of nestedness indicated that island regions contained a subset of the taxa found in mainland regions.

High Arctic rivers and lakes were predominately occupied by Chironomidae and Oligochaeta, whereas Ephemeroptera, Plecoptera, and Trichoptera taxa were more abundant at lower latitudes. Community composition was strongly associated with temperature, although geology and precipitation were also important correlates.

The strong association with temperature supports the prediction that warming will increase Arctic macroinvertebrate diversity, although low diversity on islands suggests that this increase will be limited by biogeographical constraints. Long‐term harmonised monitoring across the circumpolar region is necessary to detect such changes to diversity and inform science‐based management.
Stimulation of N2O emission via bacterial denitrification driven by acidification in estuarine sediments
Authors: Su Xiaoxuan , Wen Teng , Wang Yingmu , Xu Junshi , Cui Li , Zhang Jinbo , Xue Ximei , Ding Kai , Tang Yijia , Zhu Yong‐guan
Published: August 2021

Ocean acidification in nitrogen‐enriched estuaries has raised global concerns. For decades, biotic and abiotic denitrification in estuarine sediments has been regarded as the major ways to remove reactive nitrogen, but they occur at the expense of releasing greenhouse gas nitrous oxide (N2O). However, how these pathways respond to acidification remains poorly understood. Here we performed a N2O isotopocules analysis coupled with respiration inhibition and molecular approaches to investigate the impacts of acidification on bacterial, fungal, and chemo‐denitrification, as well as N2O emission, in estuarine sediments through a series of anoxic incubations. Results showed that acidification stimulated N2O release from sediments, which was mainly mediated by the activity of bacterial denitrifiers, whereas in neutral environments, N2O production was dominated by fungi. We also found that the contribution of chemo‐denitrification to N2O production cannot be ignored, but was not significantly affected by acidification. The mechanistic investigation further demonstrated that acidification changed the keystone taxa of sedimentary denitrifiers from N2O‐reducing to N2O‐producing ones and reduced microbial electron‐transfer efficiency during denitrification. These findings provide novel insights into how acidification stimulates N2O emission and modulates its pathways in estuarine sediments, and how it may contribute to the acceleration of global climate change in the Anthropocene.
The Economic Network Resilience of the Guanzhong Plain City Cluster, China: A network analysis from the evolutionary perspective
Authors: Ye Shanshan , Qian Zhu
Published: August 2021

This article applies the network analysis to evaluate the resilience of economic network in Guanzhong Plain City Cluster (GPCC) and examine the impact of network structural properties on economic resilience, thus providing an innovative research perspective and a theoretical framework for evaluating the economic resilience of the city cluster. A modified gravity model is introduced to construct the economic network. Three structural properties of the network, hierarchy, assortativity, and cohesion, are used to evaluate the resilience of the GPCC from 2008 to 2018 and illustrate the characteristics of the resilience. The results show that the economic network of the GPCC is strongly hierarchical with a growing trend, a declining disassortativity, and a weak cohesion. Although the network has formed a core‐peripheral structure, its hierarchy and disassortativity would result in low resilience and high vulnerability, at the risk of external shocks to the GPCC. The impact of the network structure on economic resilience is analyzed by using a regression model, which verifies the validity of applying the network theory to resilience analysis. The results suggest that improving the interactions and economic connections between core and peripheral cities will strengthen the resilience of the GPCC.
Diagnosis of von Willebrand disease: An assessment of the quality of testing in North American laboratories
Authors: Abdulrehman Jameel , Ziemba Yonah C. , Hsu Peihong , Van Cott Elizabeth M. , Plumhoff Elizabeth A. , Meijer Piet , Hollestelle Martine J. , Selby Rita
Published: August 2021

Background

Laboratory diagnosis of von Willebrand Disease (VWD) is complex. Reliance on laboratory testing can be problematic as different VWD screening panels, assays and methodologies can produce analytic variability in test results.

Objectives

To compare the degree of imprecision among the VWD assays and within the platelet binding activity (PBA) assays, to determine the consensus among the VWD assays for correct classification of sample results, and to determine consensus among laboratories’ von Willebrand factor (VWF) multimer interpretations and final interpretations of the VWD panels.

Patients/Methods

Proficiency testing results from the North American Specialized Coagulation Laboratory Association (NASCOLA) submitted by laboratories from 2010 to 2019 for all normal, type (T) 1 VWD and T2 VWD samples were analysed.

Results and Conclusions

Imprecision was lowest for VWF antigen and highest for collagen binding activity (CBA) with median coefficient of variation (CV) of 12% (interquartile range (IQR) 7%) and 23% (IQR 21%) respectively. Within the VWF PBA assays, the gain‐of‐function mutant GP1b binding (VWF: GP1bM) methods had the least imprecision (CV 9%, IQR 10%). All assays, including the various PBA methods had excellent consensus. The majority of laboratories agreed that normal (median consensus‐82%, IQR 16%) and T1 VWD (median consensus‐100%, IQR 9%) samples had normal multimer distribution. Consensus among laboratories for final interpretations was excellent for normal samples (median 81%, IQR 8%), good for T1 VWD samples (median 59%, IQR 9%), and fair for T2 VWD samples (median 44%, IQR 21%). Consensus on final interpretation decreased as sample complexity increased.
Assessment of proliferation in breast cancer: cell cycle or mitosis? An observational study
Authors: Lashen Ayat G , Toss Michael S , Katayama Ayaka , Gogna Rajan , Mongan Nigel P , Rakha Emad A
Published: August 2021

Background and aims

Proliferation is an important indicator of breast cancer (BC) prognosis, but is assessed using different approaches. Not all cells in the cell cycle are committed to division. This study aimed to characterise quantitative differences between BC cells in the cell cycle and those in mitosis and assess their relationship with other pathological parameters.

Methods and results

A cohort of BC sections (n = 621) was stained with haematoxylin and eosin and immunohistochemistry for Ki‐67. The proportion of mitotic cells and Ki‐67‐positive cells was assessed in the same areas. The Cancer Genome Atlas (TCGA) BC cohort was used to assess MKI‐67 transcriptome level and its association with the mitotic counts. The mean proportion of BC cells in the cell cycle was 24% (range = 1–90%), while the mean proportion of BC cells in mitosis was 5% (range = 0–73%). A low proportion of mitoses to whole cycling cells was associated with low histological grade tumours and the luminal A molecular subtype, while tumours with a high proportion of mitoses to the overall cycling cells were associated with triple‐negative subtype, larger tumour size, grade 3 tumours and lymph node metastasis. The high mitosis/low Ki‐67‐positive cells tumours showed a significant association with variables of poor prognosis, including high‐grade and triple‐negative subtypes.

Conclusion

The proportion of BC cells in the cell cycle and mitosis is variable. We show that not only the number of cells in the cell cycle or mitosis, but also the difference between them, provides valuable information on tumour aggressiveness.
Visual assessment of mitotic figures in breast cancer: a comparative study between light microscopy and whole slide images
Authors: Lashen Ayat , Ibrahim Asmaa , Katayama Ayaka , Ball Graham , Mihai Raluca , Toss Michael , Rakha Emad
Published: August 2021

Background and aims

Visual assessment of mitotic figures in breast cancer (BC) remains a challenge. This is expected to be more pronounced in the digital pathology era. This study aims to refine the criteria of mitotic figure recognition, particularly in whole slide images (WSI).

Method and results

Haematoxylin and eosin (H&E)‐stained BC sections (n = 506) were examined using light microscopy (LM) and WSI. A set of features for identifying mitosis in WSI and to distinguish true figures from mimickers was developed. Changes in the mitotic count between the two platforms was explored. Morphological features of mitoses were recorded separately, including absence of nuclear membrane, chromatin hairy‐like projections, shape, cytoplasmic features, mitotic cell size and relationship to surrounding cells. Each mitotic phase has its own mimickers. Fifty‐eight per cent of mitoses showed absent hairy‐like projection in WSI; however, 89% retained their ragged nuclear border, which distinguished them from mimickers including apoptotic cells, lymphocytes and dark elongated hyperchromatic structures. Mitosis in WSI showed loss of fine details, and there was a 20% average reduction rate of mitotic counts when compared to the same area on LM. Using refined mitosis recognition criteria in WSI resulted in a twofold improvement of interobserver concordance. However, when compared to LM, 19% of cases were underscored in WSIs.

Conclusions

All morphological features of mitosis should be considered to enable recognition and differentiation from their mimickers, particularly in WSI, to ensure reliable BC grading. Refining mitotic cut‐offs per specific area when using WSI, based on the degree of reduction and association with outcome, is warranted.
Rapid triage performed by nurses: Signs and symptoms associated with identifying critically ill patients in the emergency department
Authors: Moura Bruna Roberta Siqueira , Oliveira Gabriella Novelli , Medeiros Giuliana , Vieira Alexandre de Souza , Nogueira Lilia de Souza
Published: August 2021

Aim

Aim of this study is to identify signs and symptoms associated with identifying critically ill patients by rapid triage assessment performed by nurses in an emergency department.

Background

In some emergency services, the immediate assessment of critically ill patients occurs before opening the hospital formal registration and it is based on the nurse's experience. Studies on the topic are essential to improve this process.

Design

This is a cross‐sectional, quantitative study.

Methods

This study was conducted in a Brazilian emergency department in 2017. Adult patients who presented potentially life‐threatening symptoms underwent rapid triage to determine the medical urgency. Those identified as being critically ill were classified as high priority and streamed to the emergency room.

Results

A total of 154 (84.6%) patients were classified as high priority from the total of 182 evaluations. Altered state of consciousness (35.2%) and altered skin perfusion (25.3%) were frequently identified. Signs and symptoms associated with identifying critically ill patients by rapid triage were alterations in ventilation (OR 6.09; p = 0.028), neurological dysfunction (OR 44.96; p < 0.001) and pain (OR 5.80; p = 0.004).

Conclusion

Nurses should value neurological and ventilation alterations and pain in patients during rapid triage, since these signs and symptoms are associated with high care priority.
Inverse responses of species richness and niche specialization to human development
Authors: Ficken Cari D. , Jeanmougin Martin , Ciborowski Jan J. H. , Rooney Rebecca C.
Published: August 2021

Aim

Humans impact biodiversity by altering land use and introducing nonnative species. Yet the extent to which coexistence processes, such as competition and niche shifts, mediate these relationships is not clear. This study compares how human development influences wetland plant diversity by examining patterns of species richness, niche specialization and nonnative species occurrences along a human development gradient.

Location

Alberta, Canada.

Taxon

Plants.

Methods

We computed species richness and niche specialization (a measure of the range of human development extents over which a species occurs) from species occurrence data across 1582 wetlands. We tested associations between human development extent and species richness, niche specialization and nonnative species using linear mixed models. We used nonmetric multidimensional scaling ordination to examine whether community composition differed among wetlands surrounded by different human development extents.

Results

Species richness and niche specialization show contrasting relationships with human development: richness was highest and niche specialization was lowest at intermediate human development extents, suggesting that competitive ability and environmental filtering may contribute to low richness at low and high development extents, respectively. Wetlands surrounded by the highest and lowest human development extents had similar levels of richness and niche specialization, but differed in community composition. The proportion of nonnative species increased with increasing human development, alternatively suggesting that the substitution of native species by nonnatives in developed areas may contribute to reduced richness and influence community assembly.

Main conclusions

These findings demonstrate that human land development plays a major role in shaping species richness by influencing the number of nonnative species and the niche specialization of species inhabiting a wetland. Furthermore, these findings suggest that the proportion of nonnative species is an overlooked factor potentially influencing plant richness; including this variable may help clarify the inconsistent responses of diversity to human development over large spatiotemporal scales.
Novel approach to diagnosis of His bundle capture using individualized left ventricular lateral wall activation time as reference
Authors: Jastrzębski Marek , Moskal Paweł , Kukla Piotr , Bednarek Agnieszka , Kiełbasa Grzegorz , Rajzer Marek , Curila Karol , Vijayaraman Pugazhendhi
Published: August 2021

Background

During nonselective His bundle (HB) pacing, it is clinically important to confirm His bundle capture versus right ventricular septal (RVS) capture. The present study aimed to validate the hypothesis that during HB capture, left ventricular lateral wall activation time, approximated by the V6 R‐wave peak time (V6RWPT), will not be longer than the corresponding activation time during native conduction.

Methods

Consecutive patients with permanent HB pacing were recruited; cases with abnormal His‐ventricle interval or left bundle branch block were excluded. Two corresponding intervals were compared: stimulus‐V6RWPT and native HB potential‐V6RWPT. The difference between these two intervals (delta V6RWPT), which was diagnostic of lack of HB capture, was identified using receiver operating characteristic (ROC) curve analysis.

Results

A total of 723 electrocardiograms (ECGs) (219 with native rhythm, 172 with selective HB, 215 with nonselective HB, and 117 with RVS capture) were obtained from 219 patients. The native HB‐V6RWPT, nonselective‐, and selective‐HB paced V6RWPT were nearly equal, while RVS V6RWPT was 32.0 (±9.5) ms longer. The ROC curve analysis indicated delta V6RWPT > 12 ms as diagnostic of lack of HB capture (specificity of 99.1% and sensitivity of 100%). A blinded observer correctly diagnosed 96.7% (321/332) of ECGs using this criterion.

Conclusions

We validated a novel criterion for HB capture that is based on the physiological left ventricular activation time as an individualized reference. HB capture can be diagnosed when paced V6RWPT does not exceed the value obtained during native conduction by more than 12 ms, while longer paced V6RWPT indicates RVS capture.
KCTD11 inhibits progression of lung cancer by binding to β‐catenin to regulate the activity of the Wnt and Hippo pathways
Authors: Yang Man , Han Ya‐mei , Han Qiang , Rong Xue‐zhu , Liu Xiao‐fang , Ln Xu‐Yong
Published: August 2021

KCTD11 has been reported to be a potential tumour suppressor in several tumour types. However, the expression of KCTD11 and its role has not been reported in human non‐small cell lung cancer (NSCLC). Whether its potential molecular mechanism is related to its BTB domain is also unknown. The expression of KCTD11 in 139 NSCLC tissue samples was detected by immunohistochemistry, and its correlation with clinicopathological factors was analysed. The effect of KCTD11 on the biological behaviour of lung cancer cells was verified in vitro and in vivo. Its effect on the epithelial‐mesenchymal transition(EMT)process and the Wnt/β‐catenin and Hippo/YAP pathways were observed by Western blot, dual‐luciferase assay, RT‐qPCR, immunofluorescence and immunoprecipitation. KCTD11 is under‐expressed in lung cancer tissues and cells and was negatively correlated with the degree of differentiation, tumour‐node‐metastasis (TNM) stage and lymph node metastasis. Low KCTD11 expression was associated with poor prognosis. KCTD11 overexpression inhibited the proliferation and migration of lung cancer cells. Further studies indicated that KCTD11 inhibited the Wnt pathway, activated the Hippo pathway and inhibited EMT processes by inhibiting the nuclear translocation of β‐catenin and YAP. KCTD11 lost its stimulatory effect on the Hippo pathway after knock down of β‐catenin. These findings confirm that KCTD11 inhibits β‐catenin and YAP nuclear translocation as well as the malignant phenotype of lung cancer cells by interacting with β‐catenin. This provides an important experimental basis for the interaction between KCTD11, β‐catenin and YAP, further revealing the link between the Wnt and Hippo pathways.
Association of glycemic variability assessed by continuous glucose monitoring with subclinical diabetic polyneuropathy in type 2 diabetes patients
Authors: Pan Jiemin , Yan Xinfeng , Li Fengwen , Zhang Yinan , Jiang Lan , Wang Congrong
Published: August 2021

Aims/Introduction

Diabetic peripheral neuropathy is a common diabetes‐related microvascular complication. The relationship between peripheral nerve function and glucose variability is unclear. We investigated the association of glucose variability with subclinical diabetic polyneuropathy in a large‐scale sample of patients with type 2 diabetes.

Materials and Methods

We enrolled 509 individuals with type 2 diabetes who were screened for diabetic peripheral neuropathy and monitored using a continuous glucose monitoring system. Multiple glycemic variability parameters, including the mean amplitude of glycemic excursions, glucose standard deviation (SDgluc) and glucose coefficient of variation were calculated from 3‐day glucose profiles obtained from continuous glucose monitoring. All participants underwent nerve conduction studies, and the composite Z‐scores for nerve conduction parameters were calculated.

Results

Multivariate logistic regression analyses showed that SDgluc and the conventional risk factor hemoglobin A1c (HbA1c) were independently associated with abnormal nerve function, and the corresponding odds ratios (95% confidence interval) were 1.198 (1.027–1.397, SDgluc) and 1.182 (1.061–1.316, HbA1c), respectively. The composite Z‐score of nerve conduction velocity and response amplitude obviously decreased with greater SDgluc, and the composite Z‐score of distal latency significantly increased with increasing tertiles of SDgluc (all P trend <0.05). After adjusting for age, sex, body mass index, diabetes duration and HbA1c, SDgluc was independently associated with nerve conduction velocity (β = −0.124, P = 0.021).

Conclusions

The SDgluc is a significant independent contributor to subclinical diabetic polyneuropathy, in addition to conventional risk factors including diabetes duration and HbA1c.
Parasitic copepod (Lernanthropus kroyeri) on caged sea bass (Dicentrarchus labrax): An estimation of abundance and internal infestation pressure
Authors: Yavuzcan Yıldız Hijran , Korkmaz Ahmet Şeref
Published: August 2021

Infestation by parasitic copepods is a substantial problem in the cage culture of European sea bass (Dicentrarchus labrax). The Copepoda parasite, Lernanthropus kroyeri (Lernanthropidae), is one of the threats to the mariculture of sea bass. In the present study, we evaluated the data of abundance for L. kroyeri pre‐adults and adult males (PAAM) and ovigerous adult females (AFo) to estimate the internal infection pressure (IIP) in the same cage environment. The sea bass infested by L. kroyeri was collected from grow‐out sea cages located in Gulluk Bay (Turkey) in September and October 2019. Mean fish weight and length of sea bass were 75.79 ± 1.66 g and 21.40 ± 0.56 cm, respectively. The fixed lag method was used to predict the abundance of L. kroyeri adult females. The overall prevalence of L. kroyeri was 60%. The mean abundance of PAAM and AFo varied from 0.8 ± 0.24 to 2.5 ± 0.67 and 2.9 ± 0.40 to 4.3 ± 0.55, respectively. The abundance of AF was strongly correlated with PAAM. The pattern of AFo and PAAM was interpreted as an indication of the continuous infestation of L. kroyeri on sea bass. Our results showed that the correlation of AFo abundance for five consecutive weeks was significant, representing the main determinative factor for the continuity of the parasitic load. In our approach, internal infestation pressure is the quantitative estimation of the potential infective copepodids, which are mainly characterized by AF abundance and the prevalence. We predicted that the internal infestation pressure could be high, even exceeding the 50.000 × 106 potential infective copepodids for one sea cage with the fish density of 20 sea bass/m3.
Estimation of entity‐level land use and its application in urban sectoral land use footprint: A bottom‐up model with emerging geospatial data
Authors: Xie Wei , Yu Huajun , Li Yang , Dai Min , Long Xinyi , Li Nan , Wang Yutao
Published: August 2021

Land is an essential resource tomaintain the functioning of the socio‐economic system. Due to sectoral land data limitations, previous studies were primarily restricted to a coarse sectoral level or focused mainly on the global and national scales. However,fine‐scale land use data are required to provide tailored implications for municipal sustainable development. With emerging geographic data and novel methods, including point of interest data, road network data, and natural language processing, a bottom‐up model is developed to estimate the entity‐level artificial impervious land use. Then, we conducted a case study in Shanghai to investigate the spatial features, footprints, and intensities of sectoral land use. Our results indicated that 42 sectors in Shanghai had diverse spatial patterns. The transportation sector had the highest level of agglomeration among all sectors, and the manufacturing industry's adjacent land patches had higher sectoral heterogeneities than the service sector. The transportation sector had the largest direct and embodied land use footprint. The residential‐related sectors had higher land use intensities, while the high value‐added service sectors showed lower land use intensities. Our study indicates that this model offers a novel way of extracting entity‐level spatial land use information and is applicable for socio‐economic metabolism research. Future studies could incorporate remote sensing images and multiple databases to achieve higher resolution.
Barriers to the circular economy: The case of the Dutch technical and interior textiles industries
Authors: Hartley Kris , Roosendaal Jasper , Kirchherr Julian
Published: August 2021

The academic literature offers some insights about lagging progress on circular economy (CE) transition, including cultural, regulatory, market, and technical barriers. There is also an increasing body of knowledge about barriers to CE adoption that takes a macro‐level perspective across industries. However, such studies have largely neglected the industry scale. This study fills that gap by examining barriers to CE transition in the Dutch technical and interior textiles industries. Using data from 27 interviews with manufacturers and retailers, the study finds that high costs for production and marketing, along with lack of consumer interest, are among the most substantial barriers. To provide a system‐wide perspective, the study conceptualizes relationships among barriers as a chain reaction: limited knowledge of CE design options raises the difficulty and cost of delivering high‐quality circular products at the firm level, while limited availability of circular supply streams combined with the orientation of existing production systems toward linear supply chains constrain CE transition at the industry level. These findings highlight the need for intervention at levels beyond the scale of individual firms, a key implication for public policy.
Spontaneous, transient adenosine release is not enhanced in the CA1 region of hippocampus during severe ischemia models
Authors: Ganesana Mallikarjunarao , Venton B. Jill
Published: August 2021

Ischemic stroke causes damage in the brain, and a slow buildup of adenosine is neuroprotective during ischemic injury. Spontaneous, transient adenosine signaling, lasting only 3 s per event, has been discovered that increases in frequency in the caudate‐putamen during early stages of mild ischemia‐reperfusion injury. However, spontaneous adenosine changes have not been studied in the hippocampus during ischemia, an area highly susceptible to stroke. Here, we investigated changes of spontaneous, transient adenosine in the CA1 region of rat hippocampus during three different models of the varied intensity of ischemia. During the early stages of the milder bilateral common carotid artery occlusion (BCCAO) model, there were fewer spontaneous, transient adenosine, but no change in the concentration of individual events. In contrast, during the moderate 2 vertebral artery occlusion (2VAO) and severe 4 vessel occlusion (4VO) models, both the frequency of spontaneous, transient adenosine and the average event adenosine concentration decreased. Blood flow measurements validate that the ischemia models decreased blood flow, and corresponding pathological changes were observed by transmission electron microscopy (TEM). 4VO occlusion showed the most severe damage in histology and BCCAO showed the least. Overall, our data suggest that there is no enhanced spontaneous adenosine release in the hippocampus during moderate and severe ischemia, which could be due to depletion of the rapidly releasable adenosine pool. Thus, during ischemic stroke, there are fewer spontaneous adenosine events that could inhibit neurotransmission, which might lead to more damage and less neuroprotection in the hippocampus CA1 region.

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Consumer marketplaces and self‐sufficiency: Meeting consumption needs in community
Authors: Saunders Stephen G. , Sridharan Srinivas , Barrington Dani J. , Souter Regina , Shields Katherine F. , Meo Semisi , Bartram Jamie K.
Published: August 2021

Guided by a “logic of the situation” approach our research investigated a problematic situation in community to identify and critically reflect on how consumer marketplaces and self‐sufficiency meet consumption needs. In doing so, we reflect on how a situational understanding allowed the researchers to form a more complete view of how consumption needs were met in community through enabler‐led marketplaces, community‐led marketplaces and self‐sufficiency. We also re‐conceptualized our thinking as a more broadly conceived hybrid consumer marketplace to reflect our more complete understanding. We discuss the theoretical and practical implications of our more broadly conceived hybrid consumer marketplace and provide a foundation for further research into consumer marketplaces and meeting consumption needs.