bluuebunny/crossref_metadata_2025 huggingface dataset:
Blue LED causes autophagic cell death in human osteosarcoma by increasing ROS generation and dephosphorylating EGFR
Authors: He Mingyu , Yan Gege , Wang Yang , Gong Rui , Lei Hong , Yu Shuting , He Xiaoqi , Li Guanghui , Du Weijie , Ma Tianshuai , Gao Manqi , Yu Meixi , Liu Shenzhen , Xu Zihang , Idiiatullina Elina , Zagidullin Naufal , Pavlov Valentin , Cai Benzhi , Yuan Ye , Yang Lei
Published: May 2021

Osteosarcoma (OS) is the most common primary malignant bone tumour in adolescence. Lately, light‐emitting diodes (LED)‐based therapy has emerged as a new promising approach for several diseases. However, it remains unknown in human OS. Here, we found that the blue LED irradiation significantly suppressed the proliferation, migration and invasion of human OS cells, while we observed blue LED irradiation increased ROS production through increased NADPH oxidase enzymes NOX2 and NOX4, as well as decreased Catalase (CAT) expression levels. Furthermore, we revealed blue LED irradiation‐induced autophagy characterized by alterations in autophagy protein markers including Beclin‐1, LC3‐II/LC3‐I and P62. Moreover, we demonstrated an enhanced autophagic flux. The blockage of autophagy displayed a remarkable attenuation of anti‐tumour activities of blue LED irradiation. Next, ROS scavenger N‐acetyl‐L‐cysteine (NAC) and NOX inhibitor diphenyleneiodonium (DPI) blocked suppression of OS cell growth, indicating that ROS accumulation might play an essential role in blue LED‐induced autophagic OS cell death. Additionally, we observed blue LED irradiation decreased EGFR activation (phosphorylation), which in turn led to Beclin‐1 release and subsequent autophagy activation in OS cells. Analysis of EGFR colocalization with Beclin‐1 and EGFR‐immunoprecipitation (IP) assay further revealed the decreased interaction of EGFR and Beclin‐1 upon blue LED irradiation in OS cells. In addition, Beclin‐1 down‐regulation abolished the effects of blue LED irradiation on OS cells. Collectively, we concluded that blue LED irradiation exhibited anti‐tumour effects on OS by triggering ROS and EGFR/Beclin‐1‐mediated autophagy signalling pathway, representing a potential approach for human OS treatment.
Fructose‐1,6‐bisphosphatase aggravates oxidative stress‐induced apoptosis in asthma by suppressing the Nrf2 pathway
Authors: Hu Jiapeng , Wang Jia , Li Chunlu , Shang Yunxiao
Published: May 2021

Asthma is a chronic airway disease that causes excessive inflammation, oxidative stress, mucus production and bronchial epithelial cell apoptosis. Fructose‐1,6‐bisphosphatase (Fbp1) is one of the rate‐limiting enzymes in gluconeogenesis and plays a critical role in several cancers. However, its role in inflammatory diseases, such as asthma, is unclear. Here, we examined the expression, function and mechanism of action of Fbp1 in asthma. Gene Expression Omnibus (GEO) data sets revealed that Fbp1 was overexpressed in a murine model of asthma and in interleukin (IL)‐4‐ or IL‐13‐stimulated bronchial epithelial cells. We confirmed the findings in an animal model as well as Beas‐2B and 16HBE cells. In vitro investigations revealed that silencing of Fbp1 reduced apoptosis and the proportion of cells in the G2/M phase, whereas overexpression led to increases. Fbp1 knock‐down inhibited oxidative stress by activating the nuclear factor erythroid 2‐related factor 2 (Nrf2) pathway, whereas Fbp1 overexpression aggravated oxidative stress by suppressingthe Nrf2 pathway. Moreover, the Nrf2 pathway inhibitor ML385 reversed the changes caused by Fbp1 inhibition in Beas‐2B and 16HBE cells. Collectively, our data indicate that Fbp1 aggravates oxidative stress‐induced apoptosis by suppressing Nrf2 signalling, substantiating its potential as a novel therapeutic target in asthma.
Integrated microenvironment‐associated genomic profiles identify LRRC15 mediating recurrent glioblastoma‐associated macrophages infiltration
Authors: Tang Haichao , Liu Wensi , Xu Zhaoxu , Zhao Jianhang , Wang Weitao , Yu Zhaojin , Wei Minjie
Published: May 2021

Glioblastoma (GBM) is the most common malignant intracranial tumour with intrinsic infiltrative characteristics, which could lead to most patients eventually relapse. The prognosis of recurrent GBM patients remains unsatisfactory. Cancer cell infiltration and their interaction with the tumour microenvironment (TME) could promote tumour recurrence and treatment resistance. In our study, we aimed to identify potential tumour target correlated with rGBM microenvironment based on the gene expression profiles and clinical information of rGBM patients from The Cancer Genome Atlas (TCGA) database. LRRC15 gene with prognostic value was screened by univariate and multivariate analysis, and the correlation between macrophages and LRRC15 was identified as well. Furthermore, the prognosis correlation and immune characteristics of LRRC15 were validated using the Chinese Glioma Genome Atlas (CGGA) database and our clinical tissues by immunochemistry assay. Additionally, we utilized the transwell assay and carboxy fluorescein succinimidyl ester (CFSE) tracking to further confirm the effects of LRRC15 on attracting microglia/macrophages and tumour cell proliferation in the TME. Gene profiles‐based rGBM microenvironment identified that LRRC15 could act in collusion with microglia/macrophages in the rGBM microenvironment to promote the poor prognosis, especially in mesenchymal subtype, indicating the strategies of targeting LRRC15 to improve macrophages‐based immunosuppressive effects could be promising for rGBM treatments.
Uraemic extracellular vesicles augment osteogenic transdifferentiation of vascular smooth muscle cells via enhanced AKT signalling and PiT‐1 expression
Authors: Freise Christian , Querfeld Uwe , Ludwig Antje , Hamm Bernd , Schnorr Jörg , Taupitz Matthias
Published: May 2021

Extracellular vesicles (EV) function as messengers between endothelial cells (EC) and vascular smooth muscle cells (VSMC). Since chronic kidney disease (CKD) increases the risk for vascular calcifications, we investigated whether EV derived from uraemic milieu‐stimulated EC and derived from uraemic rats impact the osteogenic transdifferentiation/calcification of VSMC. For that purpose, human EC were treated with urea and indoxyl sulphate or left untreated. Experimental uraemia in rats was induced by adenine feeding. ‘Uraemic’ and control EV (EVUR; EVCTRL) were isolated from supernatants and plasma by using an exosome isolation reagent. Rat VSMC were treated with a pro‐calcifying medium (CM) with or without EV supplementation. Gene expressions, miRNA contents and protein expressions were determined by qPCR and Western blots, respectively. Calcifications were determined by colorimetric assays. Delivery of miRNA inhibitors/mimics to EV and siRNA to VSMC was achieved via transfection. EVCTRL and EVUR differed in size and miRNA contents. Contrary to EVCTRL, EC‐ and plasma‐derived EVUR significantly increased the pro‐calcifying effects of CM, including altered gene expressions of osterix, runx2, osteocalcin and SM22α. Further, EVUR enhanced the protein expression of the phosphate transporter PiT‐1 in VSMC and induced a phosphorylation of AKT and ERK. Knock down of PiT‐1 and individual inhibition of AKT and ERK signalling in VSMC blocked the pro‐calcifying effects of EVUR. Similar effects were achieved by inhibition of miR‐221/‐222 and mimicking of miR‐143/‐145 in EVUR. In conclusion, EVUR might represent an additional puzzle piece of the complex pathophysiology of vascular calcifications in CKD.
Construction of circRNA‐miRNA‐mRNA network in the pathogenesis of recurrent implantation failure using integrated bioinformatics study
Authors: Ahmadi Mohsen , Pashangzadeh Salar , Moraghebi Mahta , Sabetian Soudabeh , Shekari Mohammad , Eini Fatemeh , Salehi Ensieh , Mousavi Pegah
Published: May 2021

This research attempted to elucidate the molecular components are involved in the pathogenesis of recurrent implantation failure (RIF). We initially identified that 386 mRNAs, 144 miRNAs and 2548 circRNAs were differentially expressed (DE) in RIF and then investigated the genetic cause of the observed abnormal expression by constructing a circRNA‐miRNA‐mRNA network considering the competing endogenous RNA theory. We further analysed the upstream transcription factors and related kinases of DEmRNAs (DEMs) and demonstrated that SUZ12, AR, TP63, NANOG, and TCF3 were the top five TFs binding to these DEMs. Besides, protein‐protein interaction analysis disclosed that ACTB, CXCL10, PTGS2, CXCL12, GNG4, AGT, CXCL11, SST, PENK, and FOXM1 were the top 10 hub genes in the acquired network. Finally, we performed the functional enrichment analysis and found that arrhythmogenic right ventricular cardiomyopathy (ARVC), hypertrophic cardiomyopathy (HCM), pathways in cancer, TNF signalling pathway and steroid hormone biosynthesis were the potentially disrupted pathways in RIF patients. Optimistically, our findings may deepen our apprehensions about the underlying molecular and biological causes of RIF and provide vital clues for future laboratory and clinical experiments that will ultimately bring a better outcome for patients with RIF.
Scabies itch: an update on neuroimmune interactions and novel targets
Authors: Kim H.S. , Hashimoto T. , Fischer K. , Bernigaud C. , Chosidow O. , Yosipovitch G.
Published: May 2021

Frequently described as ‘the worst itch’ one can ever experience scabies itch is the hallmark of Sarcoptes scabiei mite infestation. Notably, the itchiness often persists for weeks despite scabicides therapy. The mechanism of scabies itch is not yet fully understood, and effective treatment modalities are still missing which can severely affect the quality of life. The aim of this review is to provide an overview of the scope of itch in scabies and highlight candidate mechanisms underlying this itch. We herein discuss scabies itch, with a focus on the nature, candidate underlying mechanisms and treatment options. We also synthesize this information with current understanding of the mechanisms contributing to non‐histaminergic itch in other conditions. Itch is a major problem in scabies and can lead to grave consequences. We provide the latest insights on host–mite interaction, secondary microbial infection and neural sensitization with special emphasis on keratinocytes and mast cells to better understand the mechanism of itch in scabies. Also, the most relevant current modalities remaining under investigation that possess promising perspectives for scabies itch (i.e. protease‐activated receptor‐2 (PAR‐2) inhibitor, Mas‐related G protein‐coupled receptor X2 (MRGPRX2) antagonist) are discussed. Greater understanding of these diverse mechanisms may provide a rational basis for the development of improved and targeted approaches to control itch in individuals with scabies.
Plantar involvement correlates with obesity, pain and impaired mobility in epidermolysis bullosa simplex: a retrospective cohort study
Authors: Reimer‐Taschenbrecker A. , Hess M. , Hotz A. , Fischer J. , Bruckner‐Tuderman L. , Has C.
Published: May 2021

Background

Epidermolysis bullosa simplex (EBS) is the most common type of EB, a group of rare genodermatoses. Affected individuals suffer from skin blistering and report a high disease burden. In some EBS subtypes, plantar keratoderma (PK) has been described.

Objectives

This study investigated the presence and correlation of PK with body mass index, pain and mobility in EBS.

Methods

Individuals (n = 157) with genetically characterized EBS were included in this retrospective cohort study, and clinical data were collected over 16 years (referral patients to the largest German EB centre). Descriptive statistics and mixed linear models were used to assess correlations.

Results

PK was found in 75.8% of patients beginning at a mean age of 4.3 years. Both focal and diffuse PK were observed, and 60% of adults with localized and severe EBS were preobese or obese, with ˜30% of patients reporting severely reduced mobility. The presence of PK, especially diffuse PK, correlated significantly with local infections, obesity, pain and requirement of a wheelchair.

Conclusion

Along with treating skin fragility and blistering, PK should be considered a potential marker of increased morbidity and may represent a target of EBS therapy development.
Sharing a written medical summary with patients on the post‐admission ward round: A qualitative study of clinician and patient experience
Authors: Crucefix Anna L. , Fleming Aaron P. L. , Lebus Caroline S. , Slowther Anne‐Marie , Fritz Zoë
Published: May 2021

Rationale, Aims and Objectives

Sharing aspects of the traditional medical record with patients has been successful in primary and antenatal care, but has not been investigated in the UK inpatient setting. Our aim was to evaluate the impact on patient and clinician experience of providing patients with a written lay summary of their care‐plan in the acute care setting.

Method

We carried out a qualitative interview study on two acute medicine wards in an NHS University Teaching Hospital for a 4‐week period in 2019. A summary record, designed in response to suggestions from doctors and patients from a previous study, was distributed to patients on the first ward round after admission. Eligible participants included all doctors and nurses working on and all patients and their families attending the acute medical units; patients were excluded if they lacked capacity to consent or were under 18. We interviewed 20 patients, 10 relatives, 10 doctors and 7 nurses.

Results

Patients felt that the summary improved their ability to remember details about their care so they could more accurately and easily update their relatives. They did not feel that the summary induced anxiety. Patient‐doctor communication was improved: patients felt empowered to ask more questions and doctors felt that it solidified their plan and encouraged them to avoid medical jargon. Most patients felt the summary included the ‘right’ amount of information. Healthcare professionals were more concerned about the risk of breaching confidentiality than patients. Doctors felt that providing summaries was time‐consuming; there were differing opinions about whether this was a worthwhile investment of time. Clinicians recognized that the traditional medical record has many roles.

Conclusions

A summary record could empower patients and improve patient‐doctor communication but would require additional clinician and administrative time.
Exploring the acceptance of COVID‐19 vaccine among healthcare workers and general population using health belief model
Authors: Al‐Metwali Basma Zuheir , Al‐Jumaili Ali Azeez , Al‐Alag Zahraa Adel , Sorofman Bernard
Published: May 2021

Rationale, aims and objectives

Little is known about hesitancy to receive the COVID‐19 vaccines. The objectives of this study were (1) to assess the perceptions of healthcare workers (HCWs) and the general population regarding the COVID‐19 vaccines, (2) to evaluate factors influencing the acceptance of vaccination using the health belief model (HBM), and (3) to qualitatively explore the suggested intervention strategies to promote the vaccination.

Methods

This was a cross‐sectional study based on electronic survey data that was collected in Iraq during December first‐19th, 2020. The electronic survey was designed using Qualtrics. HBM was followed to develop the survey items. A regression analysis was used to identify factors influencing people accepting vaccination. Thematic analysis for participant comments to an open‐ended question.

Results

A total of 1680 completed surveys were received. The mean age of 31.2 ± 9.9 years, 53.0% were female and 47.0% were male. The largest group was HCWs (45.7%), followed by general population (37.5%) and health college students (16.8%). Our findings expressed some hesitancy to receive the COVID‐19 vaccine with the acceptance rate of 61.7%. The HCWs perceived significantly higher susceptibility and severity of the COVID‐19 infection compared to the general population. The HCWs were significantly more likely than the general population to receive COVID‐19 vaccine. Concerns with proper storage was the biggest barrier to vaccine receipt. The regression analysis indicated eight factors that were significantly associated with the willingness to receive COVID‐19 vaccine: Preventive measures, perceived benefit, perceived barriers, cue to action, subjective norm, supportive of vaccination in general and having received a flu vaccine before.

Conclusions

Awareness campaign can focus on enhancing the vaccine perceived benefit, debunking misconceptions, and increasing the disease perceived severity. Additionally, the public health leaders need to minimize the perceived barriers by providing the vaccines and appeasing people concerns about their storage, effectiveness, and adverse events.
Timing of bleeding and thromboembolism associated with endoscopic submucosal dissection for gastric cancer in Japan
Authors: Shiroma Sho , Hatta Waku , Tsuji Yosuke , Yoshio Toshiyuki , Yabuuchi Yohei , Hoteya Shu , Tsuji Shigetsugu , Nagami Yasuaki , Hikichi Takuto , Kobayashi Masakuni , Morita Yoshinori , Sumiyoshi Tetsuya , Iguchi Mikitaka , Tomida Hideomi , Inoue Takuya , Mikami Tatsuya , Hasatani Kenkei , Nishikawa Jun , Matsumura Tomoaki , Nebiki Hiroko , Nakamatsu Dai , Ohnita Ken , Suzuki Haruhisa , Ueyama Hiroya , Hayashi Yoshito , Sugimoto Mitsushige , Yamaguchi Shinjiro , Michida Tomoki , Yada Tomoyuki , Asahina Yoshiro , Narasaka Toshiaki , Kuribayashi Shiko , Kiyotoki Shu , Mabe Katsuhiro , Fujishiro Mitsuhiro , Masamune Atsushi , Fujisaki Junko
Published: May 2021

Background and Aim

This study aimed to reveal the timing of bleeding and thromboembolism associated with endoscopic submucosal dissection (ESD) for early gastric cancer (EGC).

Methods

We retrospectively reviewed  10,320 patients who underwent ESD for EGC during November 2013–October 2016. We evaluated overall bleeding rates and their inter‐group differences. Factors associated with early/late (cut‐off 5 days) bleeding and thromboembolism frequency and its association with the intake of antithrombotic agents were investigated.

Results

Overall, the post‐ESD bleeding rate was 4.7% (489/10 320); the median time to post‐ESD bleeding was 4 days. The post‐ESD bleeding rates were 3.2%, 8.7%, 15.5%, and 29.9% in those not taking antithrombotic agents, those taking antiplatelet agents, those taking anticoagulants (ACs), and those taking antiplatelet agents and ACs. Warfarin (odds ratio [OR], 9.16), direct oral ACs (OR, 4.16), chronic kidney disease with hemodialysis (OR, 2.93), thienopyridine (OR, 2.25), aspirin (OR, 1.66), tumor size >30 mm (OR, 1.86), multiple tumors' resection (OR, 1.54), and tumor in the lower third of the stomach (OR, 1.40) were independent risk factors for early bleeding. The independent risk factors for late bleeding were direct oral ACs (OR, 7.42), chronic kidney disease with hemodialysis (OR, 4.99), warfarin (OR, 3.90), thienopyridine (OR, 3.09), liver cirrhosis (OR, 2.43), cilostazol (OR, 1.93), aspirin (OR, 1.92), ischemic heart disease (OR, 1.77), and male sex (OR, 1.65). There were three (0.03%) thromboembolic events (cerebral infarction = 2, transient ischemic attack = 1).

Conclusion

We revealed the timing of bleeding and risk factors for early/late bleeding and showed the thromboembolism frequency associated with ESD for EGC.
A domesticated Harbinger transposase forms a complex with HDA6 and promotes histone H3 deacetylation at genes but not TEs in Arabidopsis
Authors: Zhou Xishi , He Junna , Velanis Christos N. , Zhu Yiwang , He Yuhan , Tang Kai , Zhu Mingku , Graser Lisa , de Leau Erica , Wang Xingang , Zhang Lingrui , Andy Tao W. , Goodrich Justin , Zhu Jian‐Kang , Zhang Cui‐Jun
Published: May 2021

In eukaryotes, histone acetylation is a major modification on histone N‐terminal tails that is tightly connected to transcriptional activation. HDA6 is a histone deacetylase involved in the transcriptional regulation of genes and transposable elements (TEs) in Arabidopsis thaliana. HDA6 has been shown to participate in several complexes in plants, including a conserved SIN3 complex. Here, we uncover a novel protein complex containing HDA6, several Harbinger transposon‐derived proteins (HHP1, SANT1, SANT2, SANT3, and SANT4), and MBD domain‐containing proteins (MBD1, MBD2, and MBD4). We show that mutations of all four SANT genes in the sant‐null mutant cause increased expression of the flowering repressors FLC, MAF4, and MAF5, resulting in a late flowering phenotype. Transcriptome deep sequencing reveals that while the SANT proteins and HDA6 regulate the expression of largely overlapping sets of genes, TE silencing is unaffected in sant‐null mutants. Our global histone H3 acetylation profiling shows that SANT proteins and HDA6 modulate gene expression through deacetylation. Collectively, our findings suggest that Harbinger transposon‐derived SANT domain‐containing proteins are required for histone deacetylation and flowering time control in plants.
Does It Matter Where You Search? Twitter versus Traditional News Media
Authors: MILAS COSTAS , PANAGIOTIDIS THEODORE , DERGIADES THEOLOGOS
Published: May 2021

We compare news in Twitter with traditional news outlets and emphasize their differential impact on Eurozone's sovereign bond market. We reveal a two‐way information flow between Twitter's “Grexit” tweets and “Grexit” mentions in traditional news which suggests not only that both types of news serve as important empirical predictors for the sovereign bond market but also that the “old” (traditional news) and the “new” (Twitter) media are connected; however, the influence of Twitter on traditional news is stronger. Grexit tweets raise the Greek spread more than Grexit mentions in traditional news. Weak contagion effects are reported for Portugal and Ireland.
Role of central kisspeptin and RFRP‐3 in energy metabolism in the male Wistar rat
Authors: Cázarez‐Márquez Fernando , Eliveld Jitske , Ritsema Wayne I. G. R. , Foppen Ewout , Bossenbroek Yvonne , Pelizzari Simone , Simonneaux Valérie , Kalsbeek Andries
Published: May 2021

Kisspeptin (Kp) and (Arg)(Phe) related peptide 3 (RFRP‐3) are two RF‐amides acting in the hypothalamus to control reproduction. In the past 10 years, it has become clear that, apart from their role in reproductive physiology, both neuropeptides are also involved in the control of food intake, as well as glucose and energy metabolism. To investigate further the neural mechanisms responsible for these metabolic actions, we assessed the effect of acute i.c.v. administration of Kp or RFRP‐3 in ad lib. fed male Wistar rats on feeding behaviour, glucose and energy metabolism, circulating hormones (luteinising hormone, testosterone, insulin and corticosterone) and hypothalamic neuronal activity. Kp increased plasma testosterone levels, had an anorexigenic effect and increased lipid catabolism, as attested by a decreased respiratory exchange ratio (RER). RFRP‐3 also increased plasma testosterone levels but did not modify food intake or energy metabolism. Both RF‐amides increased endogenous glucose production, yet with no change in plasma glucose levels, suggesting that these peptides provoke not only a release of hepatic glucose, but also a change in glucose utilisation. Finally, plasma insulin and corticosterone levels did not change after the RF‐amide treatment. The Kp effects were associated with an increased c‐Fos expression in the median preoptic area and a reduction in pro‐opiomelanocortin immunostaining in the arcuate nucleus. No effects on neuronal activation were found for RFRP‐3. Our results provide further evidence that Kp is not only a very potent hypothalamic activator of reproduction, but also part of the hypothalamic circuit controlling energy metabolism.
Cyclic AMP‐dependent activation of ERK via GLP‐1 receptor signalling requires the neuroendocrine cell‐specific guanine nucleotide exchanger NCS‐RapGEF2
Authors: Xu Wenqin , Dahlke Sam P. , Emery Andrew C. , Sung Michelle , Chepurny Oleg G. , Holz George G. , Eiden Lee E.
Published: May 2021

Cyclic AMP activation of the Rap‐Braf‐MEK‐ERK pathway after signalling initiated by the neuropeptide pituitary adenylate cyclase‐activating peptide (PACAP), via the Gs‐protein coupled receptor (GsPCR) PAC1, occurs uniquely through the neuritogenic cAMP sensor Rap guanine nucleotide exchange factor 2 (NCS‐RapGEF2) in Neuroscreen‐1 (NS‐1) neuroendocrine cells. We examined the expression of other Family B GsPCRs in this cell line and assessed cAMP elevation and neuritogenesis after treatment with their cognate peptide ligands. Exposure of NS‐1 cells to the VIPR1/2 agonist vasoactive intestinal polypeptide, or the GLP1R agonist exendin‐4, did not induce neuritogenesis, or elevation of cAMP, presumably as a result of insufficient receptor protein expression. Vasoactive intestinal polypeptide and exendin‐4 did induce neuritogenesis after transduction of human VIPR1, VIPR2 and GLP1R into NS‐1 cells. Exendin‐4/GLP1R‐stimulated neuritogenesis was MEK‐ERK‐dependent (blocked by U0126), indicating its use of the cAMP→RapGEF2→ERK neuritogenic signalling pathway previously identified for PACAP/PAC1 signalling in NS‐1 cells. NCS‐RapGEF2 is expressed in the rodent insulinoma cell lines MIN6 and INS‐1, as well as in human pancreatic islets. As in NS‐1 cells, exendin‐4 caused ERK phosphorylation in INS‐1 cells. Reduction in RapGEF2 expression after RapGEF2‐shRNA treatment reduced exendin‐4‐induced ERK phosphorylation. Transcriptome analysis of INS‐1 cells after 1 hour of exposure to exendin‐4 revealed an immediate early‐gene response that was composed of both ERK‐dependent and ERK‐independent signalling targets. We propose that cAMP signalling initiated by glucagon‐like peptide 1 (GLP‐1) in pancreatic beta cells causes parallel activation of multiple cAMP effectors, including NCS‐RapGEF2, Epac and protein kinase A, to separately control various facets of GLP‐1 action, including insulin secretion and transcriptional modulation.
Suppression of axillary odor and control of axillary bacterial flora by erythritol
Authors: Fujii Tadashi , Inoue Shota , Kawai Yu , Tochio Takumi , Takahashi Kyoko
Published: May 2021

Background

Erythritol is a sugar alcohol with 4 carbon atoms that has approximately 75% of the sweetness of sucrose. It is a safe and widely used food component.

Aims

We herein investigated the growth inhibitory effects on axillary odor‐causing bacteria and axillary odor‐reducing effects of erythritol.

Methods

Growth tests in vitro were performed on Corynebacterium minutissimum, C. striatum, and Staphylococcus epidermidis. An axillary odor sensory test and axillary bacterial flora analysis were then conducted. A test product containing erythritol was applied to the axillae of 18 subjects.

Results

Erythritol significantly inhibited the growth of tested bacteria. The results of the axillary odor sensory test showed that the median values for each odor intensity of Total axillary odor intensity, Animal, Milk‐fat, Damp‐dried dust cloth, and Sourness were significantly lower in the test product application group than in the placebo group (p = 0, 0.008, 0.025, 0.004, 0, 0.001, respectively). The axillary flora analysis revealed that the relative abundance of the most dominant bacteria was lower in the test product application group than in the placebo group. Furthermore, the diversity of the total bacterial flora was significantly higher in the test product application group (p = 0.048).

Conclusion

The present results suggest that erythritol inhibits the growth of the predominant bacteria in the axilla, increases the diversity of the bacterial flora, controls the bacterial flora of the skin to a healthy abundance ratio, and reduces axillary odor.
A hypothetical role for autophagy during the day/night rhythm‐regulated melatonin synthesis in the rat pineal gland
Authors: Ge Wei , Yan Zi‐Hui , Wang Lu , Tan Shao‐Jing , Liu Jing , Reiter Russel J. , Luo Shi‐Ming , Sun Qing‐Yuan , Shen Wei
Published: May 2021

Melatonin is a highly conserved molecule that regulates day/night rhythms; it is associated with sleep improvement, reactive oxygen species (ROS) scavenging, anti‐aging effects, and seasonal and circadian rhythms and has been a hot topic of research for decades. Using single‐cell RNA sequencing, a recent study describes a single‐cell transcriptome atlas for the rat pineal gland. Based on a more comprehensive analysis of the retrieved data (Mays et al., PLoS One, 2018, 13, e0205883), results from the current study unveiled the underappreciated gene regulatory network behind different cell populations in the pineal gland. More importantly, our study here characterized, for the first time, the day/night activation of autophagy flux in the rat pineal gland, indicating a potential role of autophagy in regulating melatonin synthesis in the rat pineal gland. These findings emphasized a hypothetical role of day/night autophagy in linking the biological clock with melatonin synthesis. Furthermore, ultrastructure analysis of pinealocytes provided fascinating insights into differences in their intracellular structure between daytime and nighttime. In addition, we also provide a preliminary description of cell‐cell communication in the rat pineal gland. In summary, the current study unveils the day/night regulation of autophagy in the rat pineal gland, raising a potential role of autophagy in day/night‐regulated melatonin synthesis.
The effects of university–industry collaboration in preclinical research on pharmaceutical firms’ R&D performance: Absorptive capacity’s role
Authors: Melnychuk Tetyana , Schultz Carsten , Wirsich Alexander
Published: May 2021

Pharmaceutical firms frequently engage in preclinical research collaboration with universities. Many of these collaborative preclinical research projects are conducted by firms’ subsidiaries. In this setting, the challenge of transferring knowledge from university–industry collaborations (UICs) to internal research and development (R&D) increases, since knowledge has to be transferred twice: to the subsidiary and to the parent. To benefit from tacit and complex knowledge obtained through collaboration with academic partners, firms need to have a high absorptive capacity. However, existing research on absorptive capacity's effect on the efficacy of UIC has provided mixed results, and the knowledge transfer mechanisms remain unclear, particularly in the case of basic (or preclinical) research and of the complex knowledge transfer process from subsidiaries’ collaborative efforts. Building on the knowledge‐based view and following a multidimensional perspective of absorptive capacity, this study investigates the role a firm's capabilities play in successful university knowledge integration in a firm's internal R&D. Therefore, this paper analyzes both parent firms’ UICs and their subsidiaries’ UICs in basic (preclinical) research. The results of our longitudinal analysis of a unique panel data set of 56 global pharmaceutical firms indicate that firms do successfully exploit valuable knowledge from preclinical research UIC in internal R&D, measured by the number of performed clinical trials. This holds true for the UIC involving the parent firm and its subsidiaries. As transformative learning dimensions of absorptive capacity, high diversity in therapeutic activity and high R&D intensity levels strengthen the positive relationship between parents’ UIC and R&D performance. A high exploration intensity level of the firm and high diversity in therapeutic activity help to transfer the knowledge from subsidiaries’ preclinical research UIC to parents’ innovation projects.
Validation of the Munich Actimetry Sleep Detection Algorithm for estimating sleep–wake patterns from activity recordings
Authors: Loock Ann‐Sophie , Khan Sullivan Ameena , Reis Catia , Paiva Teresa , Ghotbi Neda , Pilz Luisa K. , Biller Anna M. , Molenda Carmen , Vuori‐Brodowski Maria T. , Roenneberg Till , Winnebeck Eva C.
Published: May 2021

Periods of sleep and wakefulness can be estimated from wrist‐locomotor activity recordings via algorithms that identify periods of relative activity and inactivity. Here, we evaluated the performance of our Munich Actimetry Sleep Detection Algorithm. The Munich Actimetry Sleep Detection Algorithm uses a moving 24–h threshold and correlation procedure estimating relatively consolidated periods of sleep and wake. The Munich Actimetry Sleep Detection Algorithm was validated against sleep logs and polysomnography. Sleep‐log validation was performed on two field samples collected over 54 and 34 days (median) in 34 adolescents and 28 young adults. Polysomnographic validation was performed on a clinical sample of 23 individuals undergoing one night of polysomnography. Epoch‐by‐epoch analyses were conducted and comparisons of sleep measures carried out via Bland‐Altman plots and correlations. Compared with sleep logs, the Munich Actimetry Sleep Detection Algorithm classified sleep with a median sensitivity of 80% (interquartile range [IQR] = 75%–86%) and specificity of 91% (87%–92%). Mean onset and offset times were highly correlated (r = .86–.91). Compared with polysomnography, the Munich Actimetry Sleep Detection Algorithm reached a median sensitivity of 92% (85%–100%) but low specificity of 33% (10%–98%), owing to the low frequency of wake episodes in the night‐time polysomnographic recordings. The Munich Actimetry Sleep Detection Algorithm overestimated sleep onset (~21 min) and underestimated wake after sleep onset (~26 min), while not performing systematically differently from polysomnography in other sleep parameters. These results demonstrate the validity of the Munich Actimetry Sleep Detection Algorithm in faithfully estimating sleep–wake patterns in field studies. With its good performance across daytime and night‐time, it enables analyses of sleep–wake patterns in long recordings performed to assess circadian and sleep regularity and is therefore an excellent objective alternative to sleep logs in field settings.
Retracted: Utility of the combined use of 3 serologic markers in the diagnosis and monitoring of chronic enteropathies in dogs
Authors: Estruch Juan , Johnson Jacqueline , Ford Sarah , Yoshimoto Sean , Mills Tracy , Bergman Philip
Published: May 2021

Background

Dogs with chronic enteropathies (CE) displayed elevated IgA seropositivity against specific markers that can be used to develop a novel test.

Objective

To assess a multivariate test to aid diagnosis of CE in dogs and to monitor treatment‐related responses.

Animals

One hundred fifty‐seven dogs with CE/inflammatory bowel disease (IBD), 24 dogs non‐IBD gastrointestinal disorders, and 33 normal dogs.

Methods

Prospective, multicenter, clinical study that enrolled dogs with gastrointestinal disorders. Serum sample collected at enrollment and up to 3 months follow‐up measuring OmpC (ACA), canine calprotectin (ACNA), and gliadin‐derived peptides (AGA) by ELISA.

Results

Seropositivity was higher in CE/IBD than normal dogs (66% vs 9% for ACA; 55% vs 15% for ACNA; and 75% vs 6% for AGA; P < .001). When comparing CE/IBD with non‐IBD disease, ACA and ACNA displayed discriminating properties (66%, 55% vs 12.5%, 29% respectively) while AGA separated CE from normal cohorts (54% vs 6%). A 3‐marker algorithm at cutoff of ACA > 15, ACNA > 6, AGA > 60 differentiates CE/IBD and normal dogs with 90% sensitivity and 96% specificity; and CE/IBD and non‐IBD dogs with 80% sensitivity and 86% specificity. Titers decreased after treatment (47%‐99% in ACA, 13%‐88% in ACNA, and 30%‐85% in AGA), changes that were concurrent with clinical improvements.

Conclusion and Clinical Importance

An assay based on combined measurements of ACA, ACNA, and AGA is useful as a noninvasive diagnostic test to distinguish dogs with CE/IBD. The test also has the potential to monitor response to treatment.
Effects of phosphatidic acid on growth and antioxidant capacity in juvenile turbot, Scophthalmus maxius L., fed with high plant protein‐based diets
Authors: Jiang Hao , Zhou Huihui , Liu Chengdong , Wang Xuan , Mai Kangsen , He Gen
Published: May 2021

Replacement of fish meal with high plant protein meal leads to reduced growth performance and health issues in farmed fish. Supplementation of functional additives has been proposed as a potential strategy to alleviate the negative effect of plant protein replacement. In this study, the effects of phosphatidic acid (PA) on growth and antioxidant capacity in juvenile turbot fed with high plant protein‐based diets were evaluated. An 11‐week feeding trial was performed using diets containing 0 (CON group), 0.05, 0.1, or 0.5% PA. The results showed that adding 0.5% PA could significantly improve the growth performance of turbot without affecting feed intake. Moreover, supplementation of 0.5% PA significantly increased the mRNA level of igf‐1 in liver. The condition factor was also enhanced in PA addition groups. The activity of lipase was increased by PA supplementation, while no difference was observed in amylase and trypsin activity. Supplying PA significantly reduced the content of malondialdehyde. Furthermore, the mRNA levels of superoxide dismutase (sod), glutathione peroxidase (gpx), and peroxiredoxin 6 (prx6) were enhanced in 0.1 and 0.5% PA groups. Our results showed that PA might be a functional additive for aquafeed with growth‐promoting and antioxidative effects.
Transgenic camelina oil is an effective source of eicosapentaenoic acid and docosahexaenoic acid in diets for farmed rainbow trout, in terms of growth, tissue fatty acid content, and fillet sensory properties
Authors: Osmond Angelisa T. Y. , Arts Michael T. , Bazinet Richard P. , Napier Johnathan A. , Han Lihua , Colombo Stefanie M.
Published: May 2021

The oilseed Camelina sativa was genetically engineered to produce eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at levels similar to fish oil (FO), which we tested as a lipid source in diets for rainbow trout. Three experimental diets were tested, a FO control, a low‐level transgenic camelina oil (LCO) diet (no FO with 12.5 g/kg camelina), and a high‐level transgenic camelina oil (HCO) diet (no FO with 130 g/kg transgenic camelina). Trout (initial weight 49.8 ± 11 g/fish) were fed for 12 weeks and were evaluated for growth performance, fatty acid content (muscle, liver, brain, and eye), and sensory properties of fillets. The final lengths and weights of fish fed LCO and HCO diets were higher compared to fish fed FO. There were no differences in weight gain, condition factor, specific growth rate, feed intake, and feed conversion ratio. EPA in muscle tissue was higher in fish fed HCO and FO diets compared to the LCO diet. Compound‐specific stable isotope analysis revealed that rainbow trout fed the FO diet stored isotopically enriched DHA compared to the lighter DHA in fish fed HCO. Trout fillets from the HCO treatment were firmer in texture and had a higher orange intensity compared to the FO group.
Nutritional evaluation of cricket, Gryllus bimaculatus, meal as fish meal substitute for olive flounder, Paralichthys olivaceus, juveniles
Authors: Jeong Seong‐Mok , Khosravi Sanaz , Mauliasari Intan Rizki , Lee Bong‐Joo , You Sang‐Guan , Lee Sang‐Min
Published: May 2021

An 8‐week feeding trial was designed to evaluate the potential of cricket meal, Gryllus bimaculatus, as a locally available unconventional source of protein in a practical diet for olive flounder, Paralichthys olivaceus. Three hundred juvenile fish (Initial weight, 33.5 ± 0.01 g) were randomly distributed into five dietary groups in triplicates (20 fish per tank) and each group was hand‐fed one of the experimental diets containing graded level of a cricket meal (CR) replacing 0, 20, 40, 60, and 80% of fish meal (FM) protein (designated as CR0, CR20, CR40, CR60, and CR80). Although replacing more than 40% of dietary FM protein resulted in lower growth rates and feed utilization efficiency, juvenile flounders fed the highest level of dietary CR (CR80) still performed as well as control group (CR0). Replacing more than 20% of FM with CR markedly reduced apparent nutrient digestibility in fish. Plasma total cholesterol concentration showed decreasing trend with increasing inclusion levels of CR in the diet. Whole body and fillet lipid content decreased with increasing levels of dietary CR. There was a remarkable enhancement in the levels of C18 fatty acids and reduction in the levels of n − 3 highly unsaturated fatty acids in the fillets of fish fed with the CR diets, which became more prominent with greater levels of dietary FM replacement. Antioxidant enzyme activities tended to increase with increasing dietary CR levels but gradually decreased when the replacement level exceeded 60%. Overall, the efficiency of CR as a promising substitute for FM in the flounder diets has been confirmed not only in relation to growth rates, but also in terms of immunopotency.
‘Rapport myopia’ in investigative interviews: Evidence from linguistic and subjective indicators of rapport
Authors: Richardson Beth H. , Nash Robert A.
Published: May 2021

Purpose

Rapport‐building has beneficial effects in investigative and security contexts. However, there remains limited understanding of the extent of agreement between different parties in their judgments of rapport.

Methods

We observed 133 mock suspect interviews, and subsequently surveyed the lead interviewer and secondary interviewer (trainees undertaking an undergraduate Policing programme), the ‘suspect’ (an actor), and an expert observer (a retired, highly experienced police detective). Each of these parties provided subjective judgments of the degree of rapport that had been formed between suspect and lead interviewer. Furthermore, we assessed whether these subjective judgments were associated with the degree of ‘Language Style Matching’ (LSM) between lead interviewer and suspect: a key linguistic measure of interpersonal synchrony.

Results

The suspect, secondary interviewer, and expert observer had generally good agreement about the degree of rapport achieved, as evidenced through significant, moderate to strong correlations between their rapport ratings. However, these parties’ rapport ratings were weakly associated with those of the lead interviewer. Our linguistic analysis provided similar results: the extent of LSM was significantly associated with suspects’ and the expert’s subjective ratings of rapport, but not with the interviewers’ ratings.

Conclusions

The findings suggest that the demands of interviewing might impede interviewers’ insight into the success of their rapport‐building efforts, leading them to overlook cues that other parties rely upon. We discuss the need for future experimental manipulations to directly test this suggestion, and we consider the value of interpersonal synchrony in defining and measuring rapport.
Hepatitis E: An update on One Health and clinical medicine
Authors: Velavan Thirumalaisamy P. , Pallerla Srinivas R. , Johne Reimar , Todt Daniel , Steinmann Eike , Schemmerer Mathias , Wenzel Jürgen J. , Hofmann Jörg , Shih James Wai Kuo , Wedemeyer Heiner , Bock Claus‐Thomas
Published: May 2021

The hepatitis E virus (HEV) is one of the main causes of acute hepatitis and the de facto global burden is underestimated. HEV‐related clinical complications are often undetected and are not considered in the differential diagnosis. Convincing findings from studies suggest that HEV is clinically relevant not only in developing countries but also in industrialized countries. Eight HEV genotypes (HEV‐1 to HEV‐8) with different human and animal hosts and other HEV‐related viruses are in circulation. Transmission routes vary by genotype and location, with large waterborne outbreaks in developing countries and zoonotic food‐borne infections in developed countries. An acute infection can be aggravated in pregnant women, organ transplant recipients, patients with pre‐existing liver disease and immunosuppressed patients. HEV during pregnancy affects the fetus and newborn with an increased risk of vertical transmission, preterm and stillbirth, neonatal jaundice and miscarriage. Hepatitis E is associated with extrahepatic manifestations that include neurological disorders such as neuralgic amyotrophy, Guillain‐Barré syndrome and encephalitis, renal injury and haematological disorders. The risk of transfusion‐transmitted HEV is increasingly recognized in Western countries where the risk may be because of a zoonosis. RNA testing of blood components is essential to determine the risk of transfusion‐transmitted HEV. There are currently no approved drugs or vaccines for HEV infections. This review focuses on updating the latest developments in zoonoses, screening and diagnostics, drugs in use and under development, and vaccines.
Adding mirabegron after intravesical onabotulinumtoxinA injection improves therapeutic effects in patients with refractory overactive bladder
Authors: Wang Chung‐Cheng , Lee Cheng‐Ling , Hwang Yi‐Ting , Kuo Hann‐Chorng
Published: May 2021

Objectives

To investigate whether adding an anticholinergic or beta‐3 agonist can improve the therapeutic effect of intravesical onabotuliumtoxinA injection in patients with refractory overactive bladder (OAB).

Methods

Ninety OAB patients who received an intravesical 100‐U onabotulinumtoxinA injection 1 month previously were consecutively invited into a prospective, randomized, open‐label study. They were randomly adding on solifenacin 5 mg daily (QD) (30 patients), mirabegron 50 mg QD (31 patients), or no medication (29 patients, control). All enrolled patients completed a 3‐day voiding diary, Overactive Bladder Symptom Score (OABSS) and Urgency Severity Scale (USS) questionnaires, Global Response Assessment (GRA) scale, and uroflowmetry at baseline (1 month after intravesical onabotulinumtoxinA injection) and 3‐, 6‐, 9‐, and 12‐month follow‐up. The primary end point was the effective therapeutic outcome defined as no OAB wet during the 12‐month period. The secondary end point included changes of GRA, OABSS, and the parameters of the voiding diary at 3 months.

Results

The baseline data were comparable among the three groups. The percentage of OAB wet in the mirabegron‐added‐on group was significantly less than that in the solifenacin‐added‐on and onabotulinumtoxinA‐only groups at four different time points (P = .02). At 3 months, the changes of GRA, OABSS, USS, urge urinary incontinence, frequency, nocturia episodes, and functional bladder capacity in the mirabegron‐added‐on group were significantly greater than those in the other groups. No serious adverse events were reported.

Conclusions

Adding mirabegron could increase the therapeutic effects, mainly on OAB symptoms and GRA scale, after intravesical onabotulinumtoxinA injection in refractory OAB patients.
Factors associated with adverse nutritional status of children in sub‐Saharan Africa: Evidence from the Demographic and Health Surveys from 31 countries
Authors: Adedokun Sulaimon T. , Yaya Sanni
Published: May 2021

Undernutrition is linked to almost half of all deaths in under‐five children. In 2019, 144 million under‐five children suffered from stunting and 47 million suffered from wasting. This study examined the factors that influence adverse nutritional status of children in sub‐Saharan Africa. The study used data from the Demographic and Health Surveys (DHS) of 31 countries, which involved 189,195 children under age 5. Binary logistic regression was used to examine the relationships between the independent variables and adverse nutritional status of children. About 26% of the children in the 31 countries in sub‐Saharan Africa considered in this study are stunted, 6% are wasted and 21% are underweight. Close to 31% of children whose mothers have no education are stunted, 9% are wasted and 28% are underweight. Adverse nutritional status of children is significantly associated with maternal age, education, household wealth, residence, antenatal care attendance, mass media exposure, child's sex and size of child at birth. This study has shown that adverse nutritional status of children is a major challenge in sub‐Saharan Africa. Efforts at improving nutritional status of children should include poverty alleviation initiatives at individual and household levels, increase in women's educational level and improvement in living conditions in rural areas.