bluuebunny/crossref_metadata_2025 huggingface dataset:
Anatomical observation and transcriptome analysis of buds reveal the association between the AP2 gene family and reproductive induction in hybrid larch (Larix kaempferi × Larix olgensis)
Authors: Hao Jun-Fei , Wang Chen , Gu Chen-Rui , Xu Dai-Xi , Zhang Lei , Zhang Han-Guo
Published: September 2022

Hybrid larch is an excellent afforestation species in northern China. The instability of seed yield is an urgent problem to be solved. The biological characteristics related to seed setting in larch are different from those in angiosperms and other gymnosperms. Studying the developmental mechanism of the larch sporophyll can deepen our understanding of conifer reproductive development and help to ensure an adequate supply of seeds in the seed orchard. The results showed that the formation of microstrobilus primordia in hybrid larch could be observed in anatomical sections collected in the middle of July. The contents of endogenous gibberellin 3 (GA3) and abscisic acid (ABA) were higher and the contents of GA4, GA7, jasmonic acid and salicylic acid were lower in multiseeded larch. Transcriptome analysis showed that transcription factors were significantly enriched in the AP2 family. There were 23 differentially expressed genes in the buds of the multiseeded and less-seeded types, and the expression of most of these genes was higher in the buds than in the needles. We conclude that mid-July is the early stage of reproductive organ development in hybrid larch and is suitable for the study of reproductive development. GA3 and ABA may be helpful for improving seed setting in larch, and 23 AP2/EREBP family genes are involved in the regulation of reproductive development in larch.
Monkeypox 2022: An Update for Nurses
Authors: Todd Betsy
Published: September 2022

The stage for the current outbreaks may have been set when global smallpox vaccination ended.
Preoperative anxiety
Authors: Friedrich Sabine , Reis Stefanie , Meybohm Patrick , Kranke Peter
Published: September 2022

Purpose of review

With first research reports dating back to the 1970s, the important role of anxiety in the perioperative period has been recognized for a long time and remains in effect.

Recent findings

The global pooled prevalence of preoperative anxiety among 14 000 surgical patients was reported to be 48%. The underlying fears among surgical patients include: fear of surgical complications, worry about the duration and degree of disability after the procedure, concerns about general anesthesia and the associated loss of control, as well as fear of waking up and experiencing discomfort and pain during or after surgery. The type and invasiveness of the planned procedure contribute to differences in preoperative anxiety levels. While preoperative anxiety is higher in younger, female patients as well as in those with a high need for information, prior exposure to anesthesia or surgery was associated with lower anxiety levels. High levels of preoperative anxiety may lead to poor postoperative pain control and increased morbidity. Due to adverse effects such as delirium, the use of benzodiazepines to manage preoperative anxiety has decreased.

Preoperative anxiety remains a critical issue in the perioperative period. Further research is needed to develop effective management strategies, which may need to be tailored to the patient's individual need.
Circ_0005615 contributes to the progression and Bortezomib resistance of multiple myeloma by sponging miR-185-5p and upregulating IRF4
Authors: Fu Caibo , Wang Jiao , Hu Min , Zhou Weilun
Published: September 2022

Circular RNAs (circRNAs) have been shown to play critical regulatory roles in multiple myeloma progression. Here, we aimed to explore the biologic role of circ_0005615 in multiple myeloma progression and its associated mechanism. Cell counting kit-8 assay was conducted to analyze the bortezomib resistance and proliferation of multiple myeloma cells. Cell proliferation was also analyzed by 5-Ethynyl-2’-deoxyuridine incorporation and flow cytometry assays. Cell apoptosis was assessed by flow cytometry. The interaction between microRNA-185-5p (miR-185-5p) and circ_0005615 or interferon regulatory factor 4 (IRF4) was verified by the dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. A xenograft tumor model was established in non-obese diabetic/server combined immune-deficiency mice to analyze the roles of circ_0005615 in tumor growth and bortezomib resistance. Circ_0005615 was upregulated in multiple myeloma tissues and cell lines. Circ_0005615 knockdown restrained the bortezomib resistance and proliferation and induced the apoptosis of multiple myeloma cells. Circ_0005615 acted as a molecular sponge for miR-185-5p, and the antitumor effects mediated by circ_0005615 knockdown were reversed by silencing miR-185-5p. IRF4 was confirmed as a direct target of miR-185-5p, and miR-185-5p overexpression-induced antitumor influences could be counteracted by IRF4 overexpression. Circ_0005615 could positively regulate IRF4 expression by sponging miR-185-5p in multiple myeloma cells. Circ_0005615 knockdown suppressed the growth and bortezomib resistance of xenograft tumors in vivo. Circ_0005615 contributed to the malignant progression and bortezomib resistance of multiple myeloma through mediating miR-185-5p/IRF4 signaling.
Strategies to Improve Enrollment and Participation in Pulmonary Rehabilitation Following a Hospitalization for COPD
Authors: Kotejoshyer Rajashree , Eve Julianna , Priya Aruna , Mazor Kathleen , Spitzer Kerry A. , Pekow Penelope S. , Pack Quinn R. , Lindenauer Peter K.
Published: September 2022

Purpose:

Pulmonary rehabilitation (PR) improves outcomes for patients with chronic obstructive pulmonary disease (COPD); however, very few patients attend. We sought to describe strategies used to promote participation in PR after a hospitalization for COPD.

Methods:

A random sample of 323 United States based PR programs was surveyed. Using a positive deviance approach, a 39-item survey was developed based on interviews with clinicians at hospitals demonstrating high rates of participation in PR. Items focused on strategies used to promote participation as well as relevant contextual factors.

Results:

Responses were received from 209 programs (65%), of which 88% (n = 184) were hospital-based outpatient facilities. Most (91%, n = 190) programs described enrolling patients continuously, and 80% (n = 167) reported a wait time from referral to the initial PR visit of <4 wk. Organization-level strategies to increase referral to PR included active surveillance (48%, n = 100) and COPD-focused staff (49%, n = 102). Provider-level strategies included clinician education (45%, n = 94), provider outreach (43%, n = 89), order sets (45%, n = 93), and automated referrals (23%, n = 48). Patient-level strategies included bedside education (53%, n = 111), flyers (49%, n = 103), motivational interviewing (33%, n = 69), financial counseling (64%, n = 134), and transportation assistance (35%, n = 73). Fewer than one-quarter (18%, n = 38) of PR programs reported using both bedside education and automatic referral, and 42% (n = 88) programs did not use either strategy.

Conclusions:

This study describes current practices in the United States, and highlights opportunities for improvement at the organization, provider, and patient level. Future research needs to demonstrate the effectiveness of these strategies, alone or in combination.
Silicone Granulomas of the Eyelids—A Case Series Illustrating a Distant Migratory Phenomenon
Authors: Neerukonda Vamsee K. , Lefebvre Daniel , Chatson George P. , Stagner Anna M.
Published: September 2022

Purpose:

Exogenous silicone has been reported to migrate to anatomic sights far from an initial injection or implantation site; this phenomenon has been rarely described in the ocular adnexa, especially in the eyelids. We document 3 additional cases of distant migration of silicone implanted elsewhere in the body to the eyelids and review the prior literature on this uncommon event.

Methods:

A retrospective chart review of 3 patients was conducted along with analysis of diagnostic histopathology. A comprehensive review of the literature regarding dissemination or migration of silicone to the eyelids in patients with either silicone breast implants or silicone facial filler use was performed.

Results:

Cases of silicone migrating to the eyelids from silicone breast implants and silicone-based facial filler are outlined in Tables 1 and 2, respectively. There are 4 total reports of women with silicone breast implants, including the 2 described here, with evidence of migration of silicone to the eyelid. Similarly, 5 cases of silicone-based facial filler with resultant migration of filler to the eyelids were identified, including 2 of the cases presented in this report (1 patient had both silicone breast implants and silicone facial filler).

Conclusion:

Silicone is chemically inert, but is known to travel throughout the body, causing a resultant foreign body response in tissue that can adversely affect even the eyelids. Silicone has a relatively characteristic histologic appearance and diagnosis of silicone granuloma highlights the importance of obtaining a thorough clinical history, particularly regarding prior cosmetic injections or breast enhancement surgery. Foreign material/foreign body granuloma is important to consider in patients with deep eyelid nodules of unclear etiology.
Consistency of pediatric pain ratings between dyads: an updated meta-analysis and metaregression
Authors: Zhou Huaqiong , Albrecht Matthew A. , Roberts Pam A. , Porter Paul , Della Phillip R.
Published: September 2022

Accurate assessment of pediatric pain remains a challenge, especially for children who are preverbal or unable to communicate because of their health condition or a language barrier. A 2008 meta-analysis of 12 studies found a moderate correlation between 3 dyads (child–caregiver, child–nurse, and caregiver–nurse). We updated this meta-analysis, adding papers published up to August 8, 2021, and that included intraclass correlation/weighted kappa statistics (ICC/WK) in addition to standard correlation. Forty studies (4,628 children) were included. Meta-analysis showed moderate pain rating consistency between child and caregiver (ICC/WK = 0.51 [0.39–0.63], correlation = 0.59 [0.52–0.65], combined = 0.55 [0.48–0.62]), and weaker consistency between child and health care provider (HCP) (ICC/WK = 0.38 [0.19–0.58], correlation = 0.49 [0.34–0.55], combined = 0.45; 95% confidence interval 0.34–0.55), and between caregiver and HCP (ICC/WK = 0.27 [−0.06 to 0.61], correlation = 0.49 [0.32 to 0.59], combined = 0.41; 95% confidence interval 0.22–0.59). There was significant heterogeneity across studies for all analyses. Metaregression revealed that recent years of publication, the pain assessment tool used by caregivers (eg, Numerical Rating Scale, Wong-Baker Faces Pain Rating Scale, and Visual Analogue Scale), and surgically related pain were each associated with greater consistency in pain ratings between child and caregiver. Pain caused by surgery was also associated with improved rating consistency between the child and HCP. This updated meta-analysis warrants pediatric pain assessment researchers to apply a comprehensive pain assessment scale Patient-Reported Outcomes Measurement Information System to acknowledge psychological and psychosocial influence on pain ratings.
Integrated analysis of intestinal microbiota and host gene expression in colorectal cancer patients
Authors: Chen Yuhui , Si Huiyan , Bao Baoshi , Li Songyan , Teng Da , Yan Yang , Hu Shidong , Xu Yingxin , Du Xiaohui
Published: September 2022

Introduction. Colorectal cancer (CRC) is one of the most common cancers and poses heavy burden on global health. The relationship between mucosal microbiome composition and colorectal gene expression are rarely studied. In this study, we integrated transcriptome data with microbiome data to investigate the relationship between them in colorectal cancer patients.

Gap statement. Previous studies have identified the contribution of gut microbiota and DEGs to the pathogenesis of CRC, but the relationship between mucosal microbiome composition and colorectal gene expression are rarely studied.

Aim. In this study, we integrated transcriptome data with microbiome data to investigate the relationship between mucosal microbiome composition and colorectal gene expression.

Methodology. First, three independent CRC gene expression profiles (GSE184093, GSE156355 and GSE146587) from Gene Expression Omnibus (GEO) were used to identify differentially expressed genes (DEGs). Second, another dataset (GSE163366) was used to analyse gut mucosal microbiome differential abundance. GO (Gene Ontology) function and KEGG (Kyoto Encyclopaedia of Genes and Genomes) pathway enrichment analyses of the DEGs were performed. Protein-protein interactions (PPIs) of the DEGs were constructed. The Spearman correlation analysis was computed between host DEGs and gut microbiome abundance data.

Results. A total of 1036 upregulated DEGs and 1194 downregulated DEGs between noncancerous tissues and cancerous tissues were identified based on the analysis. One significant module with a score 37.65 was selected out via MCODE including 41 upregulated DEGs, which are were mostly enriched in two pathways, including microtubule binding and tubulin binding. In particular, significant negative correlations are prevalent between

Fusobacterium

and the 41 DEGs with the correlation ranging between −0.54 and −0.35, and there commonly exist significant positive correlations between

Blautia

and the 41 DEGs with the correlation ranging between 0.42 and 0.54, indicating that

Fusobacterium

and

Blautia

are two of the most important microbes interacting with the gene regulation.

Conclusion. Our results demonstrate significant correlation between some gut microbes and DEGs, providing a comprehensive bioinformatics analysis of them for future investigation into the molecular mechanisms and biomarkers.
Detection of Colorectal Adenocarcinoma and Grading Dysplasia on Histopathologic Slides Using Deep Learning
Authors: Kim June , Tomita Naofumi , Suriawinata Arief A. , Hassanpour Saeed
Published: September 2022

Colorectal cancer is one of the most common types of cancer among men and women. The grading of dysplasia and the detection of adenocarcinoma are important clinical tasks in the diagnosis of colorectal cancer and shape the patients’ follow-up plans. This study evaluates the feasibility of deep learning models for the classification of colorectal lesions into four classes: benign, low-grade dysplasia, high-grade dysplasia, and adenocarcinoma. To this end, we develop a deep neural network on a training set of 655 whole-slide images of digitized colorectal resection slides from a tertiary medical institution and evaluate it on an internal test set of 234 slides, as well as on an external test set of 606 adenocarcinoma slides from The Cancer Genome Atlas database. Our model achieves an overall accuracy, sensitivity, and specificity of 95.5%, 91.0%, and 97.1% on the internal test set and an accuracy and sensitivity of 98.5% for adenocarcinoma detection task on the external test set. Our results suggest that such deep learning models can potentially assist pathologists in grading colorectal dysplasia, detecting adenocarcinoma, prescreening, and prioritizing the reviewing of suspicious cases to improve the turnaround time for patients with a high risk of colorectal cancer. Furthermore, the high sensitivity on the external test set suggests our model’s generalizability in detecting colorectal adenocarcinoma on whole slide images across different institutions.
Parallel use of pluripotent human stem cell lung and heart models provide new insights for treatment of SARS-CoV-2
Authors: Rudraraju Rajeev , Gartner Matthew J , Neil Jessica A. , Stout Elizabeth S. , Chen Joseph , Needham Elise J. , See Michael , Mackenzie-Kludas Charley , Yang Lee Leo Yi , Wang Mingyang , Pointer Hayley , Karavendzas Kathy , Abu-Bonsrah Dad , Drew Damien , Sun Yu Bo Yang , Tan Jia Ping , Sun Guizhi , Salavaty Abbas , Charitakis Natalie , Nim Hieu T. , Currie Peter D , Tham Wai-Hong , Porrello Enzo , Polo Jose , Humphrey Sean J. , Ramialison Mirana , Elliott David A. , Subbarao Kanta
Published: September 2022

SARS-CoV-2 primarily infects the respiratory tract, but pulmonary and cardiac complications occur in severe COVID-19. To elucidate molecular mechanisms in the lung and heart, we conducted paired experiments in human stem cell-derived lung alveolar type II (AT2) epithelial cell and cardiac cultures infected with SARS-CoV-2. With CRISPR- Cas9 mediated knock-out of ACE2, we demonstrated that angiotensin converting enzyme 2 (ACE2) was essential for SARS-CoV-2 infection of both cell types but further processing in lung cells required TMPRSS2 while cardiac cells required the endosomal pathway. Host responses were significantly different; transcriptome profiling and phosphoproteomics responses depended strongly on the cell type. We identified several antiviral compounds with distinct antiviral and toxicity profiles in lung AT2 and cardiac cells, highlighting the importance of using several relevant cell types for evaluation of antiviral drugs. Our data provide new insights into rational drug combinations for effective treatment of a virus that affects multiple organ systems.

One-sentence summary

Rational treatment strategies for SARS-CoV-2 derived from human PSC models
The structures of eleven (4-phenyl)piperazinium salts containing organic anions
Authors: Archana Sreeramapura D. , Kiran Kumar Haruvegowda , Yathirajan Hemmige S. , Foro Sabine , Butcher Ray J.
Published: September 2022

Eleven (4-phenyl)piperazinium salts containing organic anions have been prepared and structurally characterized, namely, 4-phenylpiperazin-1-ium 4-fluorobenzoate monohydrate, C10H15N2
+·C7H4FO2
−·H2O, 1; 4-phenylpiperazin-1-ium 4-bromobenzoate monohydrate, C10H15N2
+·C7H4BrO2
−·H2O, 3; 4-phenylpiperazin-1-ium 4-iodobenzoate, C10H15N2
+·C7H4IO2
−, 4; 4-phenylpiperazin-1-ium 4-nitrobenzoate, C10H15N2
+·C7H4NO4
−, 5; 4-phenylpiperazin-1-ium 3,5-dinitrosalicylate, C10H15N2
+·C7H3N2O7
−, 6; 4-phenylpiperazin-1-ium 3,5-dinitrobenzoate, C10H15N2
+·C7H3N2O6
−, 7; 4-phenylpiperazin-1-ium picrate, C10H15N2
+·C6H2N3O7
−, 8; 4-phenylpiperazin-1-ium benzoate monohydrate, C10H15N2
+·C7H5O2
−·H2O, 9; 4-phenylpiperazin-1-ium p-toluenesulfonate, C10H15N2
+·C7H7O3S−, 10; 4-phenylpiperazin-1-ium tartarate monohydrate, C10H15N2
+·C4H5O6
−·H2O, 11; and 4-phenylpiperazin-1-ium fumarate, C10H15N2
+·C4H3O4
−, 12. Compounds 1 and 3–12 are all 1:1 salts with the acid proton transferred to the phenylpiperaizine basic N atom (the secondary amine) with the exception of 3 where there is disorder in the proton position with it being 68% attached to the base and 32% attached to the acid. Of the structures with similar stoichiometries only 3 and 9 are isomorphous. The 4-phenyl substituent in all cases occupies an equatorial position except for 12 where it is in an axial position. The crystal chosen for structure 7 was refined as a non-merohedral twin. There is disorder in 5, 6, 10 and 11. For both 5 and 6, a nitro group is disordered and was modeled with two equivalent orientations with occupancies of 0.62 (3)/0.38 (3) and 0.690 (11)/0.310 (11), respectively. For 6, 10 and 11, this disorder is associated with the phenyl ring of the phenylpiperazinium cation with occupancies of 0.687 (10)/0.313 (10), 0.51 (7)/0.49 (7) and 0.611 (13)/389 (13), respectively. For all salts, the packing is dominated by the N—H...O hydrogen bonds formed by the cation and anion. In addition, several structures contain C—H...π (1, 3, 4, 8, 9, 10, and 12) and aromatic π–π stacking interactions (6 and 8) and one structure (5) contains a –NO2...π interaction. For all structures, the Hirshfeld surface fingerprint plots show the expected prominent spikes as a result of the N—H...O and O—H...O hydrogen bonds.
Performance analysis of a cloud-based network analytics system with multiple-source data aggregation
Authors: Fowdur Tulsi Pawan , Babooram Lavesh
Published: September 2022

Purpose

The purpose of this paper is geared towards the capture and analysis of network traffic using an array ofmachine learning (ML) and deep learning (DL) techniques to classify network traffic into different classes and predict network traffic parameters.

Design/methodology/approach

The classifier models include k-nearest neighbour (KNN), multilayer perceptron (MLP) and support vector machine (SVM), while the regression models studied are multiple linear regression (MLR) as well as MLP. The analytics were performed on both a local server and a servlet hosted on the international business machines cloud. Moreover, the local server could aggregate data from multiple devices on the network and perform collaborative ML to predict network parameters. With optimised hyperparameters, analytical models were incorporated in the cloud hosted Java servlets that operate on a client–server basis where the back-end communicates with Cloudant databases.

Findings

Regarding classification, it was found that KNN performs significantly better than MLP and SVM with a comparative precision gain of approximately 7%, when classifying both Wi-Fi and long term evolution (LTE) traffic.

Originality/value

Collaborative regression models using traffic collected from two devices were experimented and resulted in an increased average accuracy of 0.50% for all variables, with a multivariate MLP model.
Individual ambidexterity after entrepreneurial failure in COVID-19 pandemic times: the influence of current employment status
Authors: Boz Semerci Anil
Published: September 2022

Purpose

This study highlights the business failure experienced in pandemic times, its impact on entrepreneurs' perception of failure and the reciprocal relationship between entrepreneurs' perception of failure and individual ambidexterity.

Design/methodology/approach

The study provides empirical evidence on interpreting the long-term outcomes of business failure in pandemic times and develops a deeper insight by utilizing a two-year research design (time 1: 2020 and time 2: first half of 2021). It draws on data from 200 entrepreneurs who experienced business failure in the coronavirus disease 2019 (COVID-19) pandemic times which is a global crisis.

Findings

The results revealed that both challenge and hindrance appraisals of failure are associated with individual ambidexterity over time. Self-efficacy and social valuation of re-entry decisions are mediators between hindrance appraisal and individual ambidexterity on both time 1 and time 2. Moreover, there is a positive reciprocal relationship between self-efficacy and ambidexterity throughout the two time periods. In regard to participants' current employment status, hindrance appraisal, self-efficacy and perceptions of ambidexterity linkages were found to be significantly different in terms of unemployment and employment.

Originality/value

To the best of the author's knowledge, it is the first time that the individual ambidexterity of failed entrepreneurs was explored after hard times in the pandemic. It comprehensively helps to understand the importance of cognitive appraisal of hard times and identifies the perceptional and behavioral consequences of failure in entrepreneurship.
Ethnic chambers of commerce and co-creation of value: a synthesis of cultural and networking competencies
Authors: Elliot Esi , Smith Robert Spencer , Bicen Pelin
Published: September 2022

Purpose

The purpose of this paper is to explore and understand how Chambers of Commerce enhance networking among ethnic small businesses and enable the co-creation of value. This study contributes to extant research through the emergence of the concept of cultural networking competence. This study highlights how Chambers of Commerce in the USA ensures the continuation, growth and replication of ethnic small businesses through cultural networking competence.

Design/methodology/approach

This study investigates the research question by conducting qualitative research and adopting an interpretive approach of investigation in the Hispanic Chamber of Commerce in Chicago. Subjects were recruited using purposive sampling techniques via community links.

Findings

Findings show the existence of four different types of value in line with Holbrook’s typology of value – utilitarian, social, emotional and altruistic value. Because these values are culturally related, this study regards these values as cultural networking competence, which differs from general networking competence due to its focus on culture. With cultural networking competence, ethnic firms benefit from access to new domains, the creation of new opportunities, an improved effectiveness in achieving objectives beyond their own ethnic networks and the resources of other actors that can be leveraged for wider impact.

Originality/value

This study contributes to extant research through the emergence of the concept of cultural networking competence. This study highlights how Chambers of Commerce in the USA ensures the continuation, growth and replication of ethnic small businesses through cultural networking competence.
Community‐wide trait adaptation, but not plasticity, explains ant community structure in extreme environments
Authors: Ibarra‐Isassi Javier , Handa Ira Tanya , Lessard Jean‐Philippe
Published: September 2022

Quantifying trait–environment associations can help elucidate the processes underpinning the structure of species assemblages. However, most work has focused on trait variation across rather than within species, meaning that processes operating at the intraspecific levels cannot be detected. Incorporating intraspecific trait variation in community‐wide analyses can provide valuable insights about the role of morphological adaptation and plasticity on species persistence and the composition of ecological communities.

Here, we assessed geographical variation in the direction (i.e. adaptation) and strength of selection, and the magnitude of plasticity, by examining community‐wide trait variation in ant communities along an environmental gradient spanning 9° latitude in Quebec, Canada. Specifically, we measured 9 morphological traits related to foraging strategies, resource use and thermal regulation at 20 locations across temperate and boreal forests. We then examined how the mean and variance of these traits varied along temperature and precipitation gradients. Moreover, we examined how these trait–environment relationships varied across levels of organization, from individual workers (intraspecific) to colonies (intraspecific) and species (interspecific).

We observed changes in mean trait values along environmental gradients, but very little change in variance. Specifically, we observed a decrease in the mean length of antennae and an increase in the mean eye length from mild (warm and wet) to more extreme environments (cold and dry). These shifts in trait means were mostly coordinated across organizational levels (i.e. worker, colony and species). We also observed a general increase in trait variance from mild to extreme environments, but only at the species level.

Our findings suggest that stressful environmental conditions exert a strong selection pressure on ant morphology causing shifts in optimal trait values. These adaptations may enable persistence at the northern edge of the boreal forest and therefore influence the composition of these ant communities. Specifically, ants with large eyes and short antennae are overrepresented at the transition zone between the boreal forest and the tundra, possibly representing an adaptation to these more open habitats. Our study demonstrates that combining spatial and community‐wide intraspecific functional trait data provides a promising way forward to gain new insights on trait adaptations and processes underpinning community structure along environmental gradients.

Read the free Plain Language Summary for this article on the Journal blog.
The MK2 cascade mediates transient alteration in mGluR‐LTD and spatial learning in a murine model of Alzheimer's disease
Authors: Privitera Lucia , Hogg Ellen L. , Lopes Marcia , Domingos Luana B. , Gaestel Matthias , Müller Jürgen , Wall Mark J. , Corrêa Sonia A. L.
Published: September 2022

A key aim of Alzheimer disease research is to develop efficient therapies to prevent and/or delay the irreversible progression of cognitive impairments. Early deficits in long‐term potentiation (LTP) are associated with the accumulation of amyloid beta in rodent models of the disease; however, less is known about how mGluR‐mediated long‐term depression (mGluR‐LTD) is affected. In this study, we have found that mGluR‐LTD is enhanced in the APPswe/PS1dE9 mouse at 7 but returns to wild‐type levels at 13 months of age. This transient over‐activation of mGluR signalling is coupled with impaired LTP and shifts the dynamic range of synapses towards depression. These alterations in synaptic plasticity are associated with an inability to utilize cues in a spatial learning task. The transient dysregulation of plasticity can be prevented by genetic deletion of the MAP kinase‐activated protein kinase 2 (MK2), a substrate of p38 MAPK, demonstrating that manipulating the mGluR‐p38 MAPK‐MK2 cascade at 7 months can prevent the shift in synapse dynamic range. Our work reveals the MK2 cascade as a potential pharmacological target to correct the over‐activation of mGluR signalling.
Mechanical stress‐induced hemolysis of bovine blood is donor‐dependent
Authors: Li Zengji , Hu Jie , Kamberi Marika , Rapoza Richard J.
Published: September 2022

Introduction

In vitro hemolysis testing is an essential method for assessing the hemolytic potential of blood pumps, but has poor reproducibility. Further investigations are needed to determine the sources and extent of variability and to find a practical way to reduce the variation.

Methods

A small volume blood circulating loop driven by a Centrimag pump was established to provide relatively higher hemolysis readouts within a short run time and to be able to sequentially perform multiple repeated hemolysis tests in a working day.

Results

The repeatability with this system was demonstrated as the %RSD at 4.3% for the NIH or MIH from three repeated tests using the same blood. The bovine blood from different randomly selected donors was tested and gave more than a two‐fold difference in NIH results (0.077 vs. 0.032 g/100 L) under the same testing conditions and same pump. This wide variation in hemolysis using bovine blood from different donors happened repeatedly. More importantly, it was observed that the difference in hemolysis test results using the blood drawn from the same donor on multiple days was narrow although the native hematocrits varied. The %RSD of NIH values obtained on five different days were 6.8%, 8.4%, 11.5%, and 7.8% for donor‐specific blood from donors 1 to 4, respectively.

Conclusion

The study results indicate that the mechanical stress‐induced hemolysis behavior is donor‐dependent. It has been also demonstrated that the reproducibility of in vitro hemolysis testing can be improved when the blood drawn from same donor is used.
Having time to oneself in times of extended togetherness: Solitude experiences during the COVID‐19 pandemic
Authors: Choi Yoonseok , Pauly Theresa , Zambrano Garza Elizabeth , Broen Tiana , Gerstorf Denis , Hoppmann Christiane A.
Published: September 2022

This study investigated how time to oneself (solitude) is experienced under conditions of extended togetherness with household members during the pandemic. Both structural (living arrangements) and qualitative characteristics (relationship quality and conflict) were examined for their association with solitude desire and daily solitude–affect links. We expected that people living with others and those with more high‐quality as well as those with more conflictual relationships would report better affect quality when experiencing solitude. A Canadian adult lifespan sample (N = 141; Mage = 38.43 years, SDage = 17.51; 81% female; 73% White; data collected from April to August 2020) provided information on household size and relationship characteristics and completed repeated daily life assessments of solitude desire, solitude, and affect. Findings show that living arrangements were not associated with an increased desire for solitude or better affect quality from solitude. Individuals reporting higher relationship quality and individuals reporting more conflict showed more favorable affect quality on days when they had time in solitude than individuals reporting lower quality relationships and lower conflict. Findings add to the growing solitude literature by delineating who seeks and benefits from solitude, and under what conditions.
Genetic enhancement, human extinction, and the best interests of posthumanity
Authors: Rueda Jon
Published: September 2022

The cumulative impact of enhancement technologies may alter the human species in the very long‐term future. In this article, I will start showing how radical genetic enhancements may accelerate the conversion into a novel species. I will also clarify the concepts of ‘biological species’, ‘transhuman’ and ‘posthuman’. Then, I will summarize some ethical arguments for creating a transhuman or posthuman species with a substantially higher level of well‐being than the human one. In particular, I will present what I shall call the Principle of the Best Interests of Posthumanity, which states that the enhancement of the human and transhuman species must be directed towards the creation of a posthuman existence that is substantially more valuable than its predecessors. I suggest that human extinction may be considered, within that principle, as one of the best interests of posthumanity. Finally, I will develop three objections that make that principle unattractive and that show that pursuing a full‐blown programme of posthuman evolution is ethically flawed.
The sanctity of life as a sacred value
Authors: Clarke Steve
Published: September 2022

The doctrine of the sanctity of life has traditionally been characterised as a Judeo‐Christian doctrine that has it that bodily human life is an intrinsic good and that it is always impermissible to kill an innocent human. Abortion and euthanasia are often assumed to violate the doctrine. The doctrine is usually understood as being derived from religious dogma and, as such, not amenable to debate. I show that this characterisation of the doctrine is problematic in a number of ways, and I go on to rethink the doctrine. In doing so I follow in the footsteps of Ronald Dworkin, who offered a characterisation of the doctrine in his 1993 Life's Dominion, drawing on a conceptualisation of sacredness that is radically different from standard ones and not dependent on religious dogma. I'll argue that although Dworkin's efforts have much to recommend, his conceptualisation of sacredness is inadequate. Dworkin attempted to reconceptualise sacredness ‘from the armchair’. Here I explain how sacred values are thought of in anthropology and psychology and argue that the sanctity of human life should be understood in the same way. I'll explain how doing so allows us to resolve a number of conceptual problems that bedevil standard characterisations of the doctrine of the sanctity of life. I'll also consider the possibility of a compromise over the sanctity of human life, and as a consequence, compromise over the permissibility of abortion and euthanasia. I'll argue that such compromise is possible, albeit difficult to achieve.
Nucleic acid–triggered tumoral immunity propagates pH‐selective therapeutic antibodies through tumor‐driven epitope spreading
Authors: Furuya Genta , Katoh Hiroto , Atsumi Shinichiro , Hashimoto Itaru , Komura Daisuke , Hatanaka Ryo , Senga Shogo , Hayashi Shuto , Akita Shoji , Matsumura Hirofumi , Miura Akihiro , Mita Hideaki , Nakakido Makoto , Nagatoishi Satoru , Sugiyama Akira , Suzuki Ryohei , Konishi Hiroki , Yamamoto Asami , Abe Hiroyuki , Hiraoka Nobuyoshi , Aoki Kazunori , Kato Yasumasa , Seto Yasuyuki , Yoshimura Chihoko , Miyadera Kazutaka , Tsumoto Kouhei , Ushiku Tetsuo , Ishikawa Shumpei
Published: September 2022

Important roles of humoral tumor immunity are often pointed out; however, precise profiles of dominant antigens and developmental mechanisms remain elusive. We systematically investigated the humoral antigens of dominant intratumor immunoglobulin clones found in human cancers. We found that approximately half of the corresponding antigens were restricted to strongly and densely negatively charged polymers, resulting in simultaneous reactivities of the antibodies to both densely sulfated glycosaminoglycans (dsGAGs) and nucleic acids (NAs). These anti‐dsGAG/NA antibodies matured and expanded via intratumoral immunological driving force of innate immunity via NAs. These human cancer–derived antibodies exhibited acidic pH–selective affinity across both antigens and showed specific reactivity to diverse spectrums of human tumor cells. The antibody‐drug conjugate exerted therapeutic effects against multiple cancers in vivo by targeting cell surface dsGAG antigens. This study reveals that intratumoral immunological reactions propagate tumor‐oriented immunoglobulin clones and demonstrates a new therapeutic modality for the universal treatment of human malignancies.
A contrastive learning‐based attention generative adversarial network for defect detection in colour‐patterned fabric
Authors: Zhang Hongwei , Chen Xiwei , Lu Shuai , Yao Le , Chen Xia
Published: September 2022

The pattern style of colour‐patterned fabrics is varied. Defective fabric samples are scarce in the production of small batches of colour‐patterned fabrics. Therefore, the unsupervised defect‐detection method for colour‐patterned fabric has attracted wide attention. Several unsupervised defect‐detection methods for colour‐patterned fabrics based on convolutional neural networks have been proposed. However, convolutional neural network methods cannot learn long‐range semantic information interaction well because of the intrinsic locality of convolution operations. Besides, as the number of layers in the convolutional neural network increases, the feature maps become more and more complex. Convolutional neural networks experience difficulties in coordinating numerous parameters and extracting key features from complex feature maps. Both these problems reduce the accuracy of the model for detecting defects in colour‐patterned fabrics. In this paper, we propose a Contrastive Learning‐based Attention Generative Adversarial Network (CLAGAN) for defect detection in colour‐patterned fabrics. The CLAGAN possesses two important parts: contrastive learning and a channel attention module. Contrastive learning captures long‐range dependencies by calculating the cosine similarity between different features. The channel attention module assigns different weights to each channel of the feature maps, and it enables the model to extract key features from those feature maps. The experimental results verified the effectiveness of the CLAGAN. It obtained values of 38.25% for intersection over union and of 51.67% for the F1‐measure on the YDFID‐2 public dataset.
In vivo molecular imaging of cardiac angiogenesis in persons with and without type 2 diabetes: A cross‐sectional 68 Ga‐RGD‐PET study
Authors: Laursen Jens Christian , Rasmussen Ida Kirstine Bull , Zobel Emilie Hein , Hasbak Philip , Holmvang Lene , Hansen Christian Stevns , von Scholten Bernt Johan , Frimodt‐Møller Marie , Rossing Peter , Hansen Tine Willum , Kjaer Andreas , Ripa Rasmus Sejersten
Published: September 2022

Aims

To assess cardiac angiogenesis in type 2 diabetes by positron emission tomography (PET) tracer [68Ga]Ga‐NODAGA‐E[(cRGDyK)]2 (68Ga‐RGD) imaging.

Methods

Cross‐sectional study including 20 persons with type 2 diabetes and 10 non‐diabetic controls (CONs). Primary prespecified outcome was difference in cardiac angiogenesis (cardiac 68Ga‐RGD mean target‐to‐background ratio [TBRmean]) between type 2 diabetes and CONs. Secondary outcome was to investigate associations between cardiac angiogenesis and kidney function and other risk factors.

Results

Participants with type 2 diabetes had a mean ± SD age of 61 ± 9 years, 30% were women, median (IQR) diabetes duration of 11 (6–19) years and 3 (15%) had a history of cardiovascular disease. The CONs had comparable age and sex distribution to the participants with type 2 diabetes, and none had a history of coronary artery disease. Myocardial flow reserve was lower in type 2 diabetes (2.7 ± 0.6) compared with CONs (3.4 ± 1.2) ( p  = 0.03) and coronary artery calcium score was higher (562 [142–905] vs. 1 [0–150] p  = 0.04). Cardiac 68Ga‐RGD TBRmean was similar in participants with type 2 diabetes (0.89 ± 0.09) and CONs (0.89 ± 0.10) ( p  = 0.92). Cardiac 68Ga‐RGD TBRmean was not associated with estimated glomerular filtration rate, urine albumin creatinine ratio, cardiovascular disease, coronary artery calcium score or baroreflex sensitivity, neither in pooled analyses nor in type 2 diabetes.

Conclusions

Cardiac angiogenesis, evaluated with 68Ga‐RGD PET, was similar in type 2 diabetes and CONs. Cardiac angiogenesis was not associated with kidney function or other risk markers in pooled analyses or in analyses restricted to type 2 diabetes.
Lysine demethylase KDM5B down‐regulates SIRT3‐mediated mitochondrial glucose and lipid metabolism in diabetic neuropathy
Authors: Jiao Yang , Li Yi‐Ze , Zhang Yue‐Hua , Cui Wei , Li Qing , Xie Ke‐Liang , Yu Yang , Yu Yong‐Hao
Published: September 2022

Background

Diabetic peripheral neuropathy (DPN) is a common neurological complication of diabetes mellitus without efficient interventions. Both lysine demethylase 5B (KDM5B) and sirtuin‐3 (SIRT3) have been found to regulate islet function and glucose homeostasis. KDM5B was predicted to bind to the SIRT3 promoter by bioinformatics. Here, we investigated whether KDM5B affected DPN development via modulating SIRT3.

Methods

The db/db mice and high glucose‐stimulated Schwann cells (RSC96) were used as in vivo and in vitro models of DPN, respectively. Glucose level, glucose and insulin tolerance of mice were measured. Neurological function was evaluated by motor nerve conduction velocity (MNCV), tactile allodynia assay and thermal sensitivity assay. Adenosine triphosphate level, oxygen consumption rate, extracellular acidification rate, β‐oxidation rate, acetyl‐CoA level, acetylation levels and activities of long‐chain acyl CoA dehydrogenase (LCAD) and pyruvate dehydrogenase (PDH) were detected. Methyl thiazolyl tetrazolium assay was adopted to determine cell viability. Reactive oxygen species (ROS) production was detected by MitoSox staining. Western blotting for measuring target protein levels. Molecular mechanisms were investigated by co‐immunoprecipitine (Co‐IP), chromatin immunoprecipitation (ChIP) and luciferase reporter assay.

Results

KDM5B was up‐regulated, while SIRT3 was down‐regulated in DPN models. SIRT3 overexpression or AMPK activation ameliorated mitochondrial metabolism dysfunction and ROS overproduction during DPN. KDM5B overexpression triggered mitochondrial metabolism disorder and oxidative stress via directly transcriptional inhibiting SIRT3 expression by demethylating H3K4me3 or indirectly repressing AMPK pathway‐regulated SIRT3 expression.

Conclusion

KDM5B contributes to DPN via regulating SIRT3‐mediated mitochondrial glucose and lipid metabolism. KDM5B inhibition may be an effective intervention for DPN.
Higher turnout increases incumbency advantages: Evidence from mayoral elections
Authors: Frank Marco , Stadelmann David , Torgler Benno
Published: September 2022

We analyze the effect of electoral turnout on incumbency advantages by exploring mayoral elections in the German state of Bavaria. Mayors are elected by majority rule in two‐round (runoff) elections. Between the first and second ballot of the mayoral election in March 2020, the state government announced an official state of emergency. In the second ballot, voting in person was prohibited and only postal voting was possible. To construct an instrument for electoral turnout, we use a difference‐in‐differences strategy by contrasting turnout in the first and second ballot in 2020 with the first and second ballots from previous elections. We use this instrument to analyze the causal effect of turnout on incumbent vote shares. A 10‐percentage point increase in turnout leads to a statistically robust 3.4 percentage point higher vote share for incumbent mayors highlighting the relevance of turnout‐related incumbency advantages.
A global meta‐analysis reveals higher variation in breeding phenology in urban birds than in their non‐urban neighbours
Authors: Capilla‐Lasheras Pablo , Thompson Megan J. , Sánchez‐Tójar Alfredo , Haddou Yacob , Branston Claire J. , Réale Denis , Charmantier Anne , Dominoni Davide M.
Published: September 2022

Cities pose a major ecological challenge for wildlife worldwide. Phenotypic variation, which can result from underlying genetic variation or plasticity, is an important metric to understand eco‐evolutionary responses to environmental change. Recent work suggests that urban populations might have higher levels of phenotypic variation than non‐urban counterparts. This prediction, however, has never been tested across species nor over a broad geographical range. Here, we conducted a meta‐analysis of the avian literature to compare urban versus non‐urban means and variation in phenology (i.e. lay date) and reproductive effort (i.e. clutch size, number of fledglings). First, we show that urban populations reproduce earlier and have smaller broods than non‐urban conspecifics. Second, we show that urban populations have higher phenotypic variation in laying date than non‐urban populations. This result arises from differences between populations within breeding seasons, conceivably due to higher landscape heterogeneity in urban habitats. These findings reveal a novel effect of urbanisation on animal life histories with potential implications for species adaptation to urban environments (which will require further investigation). The higher variation in phenology in birds subjected to urban disturbance could result from plastic responses to a heterogeneous environment, or from higher genetic variation in phenology, possibly linked to higher evolutionary potential.
The colonisation of saline waters is associated with lowered immune responses in aquatic beetles
Authors: Botella‐Cruz María , Pallarés Susana , Velasco Josefa , Moody A. John , Billington Richard , Millán Andrés , Bilton David T.
Published: September 2022

The immune response represents a suite of evolved traits that can involve energetic and evolutionary trade‐offs with other energy‐demanding and fitness‐related processes. Here, we tested the hypothesis that aquatic beetles living in inland hypersaline habitats have lower immune capacity than freshwater congeners.

Phenoloxidase activity, encapsulation response and antimicrobial peptide activity were compared in freshwater/hypersaline species pairs with differing osmoregulatory capacity and cuticular waterproofing properties in the genera Nebrioporus (Dytiscidae) and Enochrus (Hydrophilidae), independent evolutionary lineages that have colonised saline media separately.

Hypersaline species (N. ceresyi and E. jesusarribasi) showed significantly lower phenoloxidase activity and antimicrobial peptide responses than their freshwater relatives (N. clarkii and E. salomonis). Encapsulation responses in freshwater species also appeared to be higher than in hypersaline relatives.

Our results reinforce the complex nature of immune responses and suggest that adaptation to saline environments may have involved a trade‐off between osmoregulation and investment in immune defences, but also are consistent with relaxed selection pressures on basal immune responses resulting from lower microbial infection load in saline habitats. In addition, the more resistant cuticle of species occupying such habitats may protect against the entry of parasites, reducing selection pressure on immunity.

Because the evolution of salinity tolerance is associated with reduced immune capacity, saline specialists may be particularly vulnerable to the dilution of saline waters and consequent changes in pathogen communities and load following colonisation by more generalist microorganisms.