bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractCyclic 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

AbstractBackgroundErythritol 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.AimsWe herein investigated the growth inhibitory effects on axillary odor‐causing bacteria and axillary odor‐reducing effects of erythritol.MethodsGrowth 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.ResultsErythritol 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).ConclusionThe 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

AbstractMelatonin 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

AbstractPharmaceutical 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

AbstractPeriods 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

AbstractBackgroundDogs with chronic enteropathies (CE) displayed elevated IgA seropositivity against specific markers that can be used to develop a novel test.ObjectiveTo assess a multivariate test to aid diagnosis of CE in dogs and to monitor treatment‐related responses.AnimalsOne hundred fifty‐seven dogs with CE/inflammatory bowel disease (IBD), 24 dogs non‐IBD gastrointestinal disorders, and 33 normal dogs.MethodsProspective, 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.ResultsSeropositivity 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 ImportanceAn 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

AbstractReplacement 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

AbstractThe 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

AbstractAn 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

PurposeRapport‐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.MethodsWe 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.ResultsThe 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.ConclusionsThe 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

AbstractThe 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

AbstractObjectivesTo 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).MethodsNinety 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.ResultsThe 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.ConclusionsAdding mirabegron could increase the therapeutic effects, mainly on OAB symptoms and GRA scale, after intravesical onabotulinumtoxinA injection in refractory OAB patients.