bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antimicrobial d-amino acid oxidase-derived peptides specify gut microbiota
Authors: Murtas Giulia , Sacchi Silvia , Tedeschi Gabriella , Maffioli Elisa , Notomista Eugenio , Cafaro Valeria , Abbondi Monica , Mothet Jean-Pierre , Pollegioni Loredano 
Published: January 2021

AbstractThe flavoenzyme d-amino acid oxidase (DAAO) is deputed to the degradation of d-enantiomers of amino acids. DAAO plays various relevant physiological roles in different organisms and tissues. Thus, it has been recently suggested that the goblet cells of the mucosal epithelia secrete into the lumen of intestine, a processed and active form of DAAO that uses the intestinal d-amino acids to generate hydrogen peroxide (H2O2), an immune messenger that helps fighting gut pathogens, and by doing so controls the homeostasis of gut microbiota. Here, we show that the DAAO form lacking the 1–16 amino acid residues (the putative secretion signal) is unstable and inactive, and that DAAO is present in the epithelial layer and the mucosa of mouse gut, where it is largely proteolyzed. In silico predicted DAAO-derived antimicrobial peptides show activity against various Gram-positive and Gram-negative bacteria but not on Lactobacilli species, which represent the commensal microbiota. Peptidomic analysis reveals the presence of such peptides in the mucosal fraction. Collectively, we identify a novel mechanism for gut microbiota selection implying DAAO-derived antimicrobial peptides which are generated by intestinal proteases and that are secreted in the gut lumen. In conclusion, we herein report an additional, ancillary role for mammalian DAAO, unrelated to its enzymatic activity.
Increased hospital treatment volume of splenic injury predicts higher rates of successful non-operative management and reduces hospital length of stay: a Swiss Trauma Registry analysis
Authors: Lavanchy Joël L. , Delafontaine Luciane , Haltmeier Tobias , Bednarski Piotr , Schnüriger Beat ,   the Swiss Trauma Registry
Published: January 2021

Abstract
Purpose
First time analysis of the epidemiology, management and outcomes of patients with splenic injuries in Switzerland. This study aims to assess the effect of hospital treatment volume on successful non-operative management (NOM) in splenic injuries.

Methods
A multicentric registry-based study including all patients with splenic injuries entered into the Swiss Trauma Registry from 2015 to 2018 was conducted. Patients were stratified according to the hospitals treatment volume of splenic injuries. Primary outcome was the rate of successful NOM.

Results
During the 4-year study period, 652 patients with splenic injury were included in the study. Median age of the study population was 42 (IQR 27–59) years, and median ISS was 26 (20–34). The overall rate of successful NOM was 86.5%. Median HLOS was 13 (8–21) days. In-hospital mortality was 7.2% (n = 47). The mean number of patients with splenic injuries per center and year was 14. Five out of 12 Level I trauma centers treating more patients than the mean (≥ 15/year) were defined as high-volume centers.
Multivariable analysis adjusting for differences in baseline and injury characteristics revealed treatment in a high-volume center as an independent predictor for successful NOM (OR 2.15, 95% CI 1.28–3.60, p = 0.004) and shorter HLOS (RC − 2.39, 95% CI − 4.91/− 0.48, p = 0.017), however, not for reduced in-hospital mortality (OR 0.92, 95% CI 0.39–2.18, p = 0.845).

Conclusion
Higher hospital treatment volume was associated with a higher rate of NOM and shorter HLOS, but not lower mortality. These results constitute the basis for further quality improvement in the care of splenic injury patients within the trauma system in Switzerland.
3D culture conditions support Kaposi’s sarcoma herpesvirus (KSHV) maintenance and viral spread in endothelial cells
Authors: Dubich Tatyana , Dittrich Anne , Bousset Kristine , Geffers Robert , Büsche Guntram , Köster Mario , Hauser Hansjörg , Schulz Thomas F. , Wirth Dagmar 
Published: January 2021

Abstract
Kaposi’s sarcoma–associated herpesvirus (KSHV) is a human tumorigenic virus and the etiological agent of an endothelial tumor (Kaposi’s sarcoma) and two B cell proliferative diseases (primary effusion lymphoma and multicentric Castleman’s disease). While in patients with late stage of Kaposi’s sarcoma the majority of spindle cells are KSHV-infected, viral copies are rapidly lost in vitro, both upon culture of tumor-derived cells or from newly infected endothelial cells. We addressed this discrepancy by investigating a KSHV-infected endothelial cell line in various culture conditions and in tumors of xenografted mice. We show that, in contrast to two-dimensional endothelial cell cultures, KSHV genomes are maintained under 3D cell culture conditions and in vivo. Additionally, an increased rate of newly infected cells was detected in 3D cell culture. Furthermore, we show that the PI3K/Akt/mTOR and ATM/γH2AX pathways are modulated and support an improved KSHV persistence in 3D cell culture. These mechanisms may contribute to the persistence of KSHV in tumor tissue in vivo and provide a novel target for KS specific therapeutic interventions.

Key messages

In vivo maintenance of episomal KSHV can be mimicked in 3D spheroid cultures

3D maintenance of KSHV is associated with an increased de novo infection frequency

PI3K/Akt/mTOR and ATM/ γH2AX pathways contribute to viral maintenance
Animal models for pelvic organ prolapse: systematic review
Authors: Mori da Cunha Marina Gabriela M. C. , Mackova Katerina , Hympanova Lucie Hajkova , Bortolini Maria Augusta T. , Deprest Jan 
Published: January 2021

AbstractIntroduction and hypothesisWe aimed to summarize the knowledge on the pathogenesis of pelvic organ prolapse (POP) generated in animal models.MethodsWe searched MEDLINE, Embase, Cochrane and the Web of Science to establish what animal models are used in the study of suggested risk factors for the development of POP, including pregnancy, labor, delivery, parity, aging and menopause. Lack of methodologic uniformity precluded meta-analysis; hence, results are presented as a narrative review.ResultsA total of 7426 studies were identified, of which 51 were included in the analysis. Pregnancy has a measurable and consistent effect across species. In rats, simulated vaginal delivery induces structural changes in the pelvic floor, without complete recovery of the vaginal muscular layer and its microvasculature, though it does not induce POP. In sheep, first vaginal delivery has a measurable effect on vaginal compliance; measured effects of additional deliveries are inconsistent. Squirrel monkeys can develop POP. Denervation of their levator ani muscle facilitates this process in animals that delivered vaginally. The models used do not develop spontaneous menopause, so it is induced by ovariectomy. Effects of menopause depend on the age at ovariectomy and the interval to measurement. In several species menopause is associated with an increase in collagen content in the longer term. In rodents there were no measurable effects of age apart of elastin changes. We found no usable data for other species.ConclusionIn several species there are measurable effects of pregnancy, delivery and iatrogenic menopause. Squirrel monkeys can develop spontaneous prolapse.
Urinary incontinence 6 weeks to 1 year post-partum: prevalence, experience of bother, beliefs, and help-seeking behavior
Authors: Moossdorff-Steinhauser Heidi F. A. , Berghmans Bary C. M. , Spaanderman Marc E. A. , Bols Esther M. J. 
Published: January 2021

Abstract
Introduction and hypothesis
Post-partum, women often experience urinary incontinence (UI). However, the association between experienced UI bother and UI beliefs and help-seeking behavior is less known. Therefore, we aim to investigate the prevalence of self-reported UI, the level of experienced bother and beliefs, to explain help-seeking behavior for UI in women in the Netherlands from 6 weeks to one year post-partum.

Methods
A digital survey among post-partum women, shared on social media, was used for recruitment. The survey consists of: 1. demographic variables, 2. International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF), 3. ICIQ Lower Urinary Tract Symptoms Quality of Life (ICIQ-LUTSqol), and 4. questions on beliefs and help-seeking behavior. For analysis, descriptive statistics and the independent samples t-test were used to determine differences between help- and non-help-seekers.

Results
415 women filled in the survey. The mean age was 30.6 years (SD 4.0, range 21–40) of which 48.2% was primiparous. The overall prevalence of UI was 57.1% (95% confidence interval (CI) (52.3–61.8)). Primiparous women reported a statistically significantly lower overall prevalence than multiparous women, 52.0% and 61.9% respectively (p = .043). UI was reported as bothersome in 38% of women, 25% of all women sought help. Help-seeking women showed significantly higher scores for bother, measured by the ICIQ-UI SF, than non-help seekers (p = .001).

Conclusions
More than half of all post-partum women in the Netherlands from 6 weeks to one year post childbirth experience UI (57.1%), 38% classified their UI as bothersome. In total 25% of UI women sought professional help.
The enzyme subunit SubA of Shiga toxin-producing E. coli strains demonstrates comparable intracellular transport and cytotoxic activity as the holotoxin SubAB in HeLa and HCT116 cells in vitro
Authors: Sessler Katharina , Papatheodorou Panagiotis , Wondany Fanny , Krause Maike , Noettger Sabrina , Bernhard Denise , Michaelis Jens , Schmidt Herbert , Barth Holger 
Published: January 2021

AbstractThe subtilase cytotoxin (SubAB) is secreted by certain Shiga toxin-producing Escherichia coli (STEC) strains and is composed of the enzymatically active subunit SubA and the pentameric binding/transport subunit SubB. We previously demonstrated that SubA (10 µg/ml), in the absence of SubB, binds and intoxicates the human cervix cancer-derived epithelial cell line HeLa. However, the cellular and molecular mechanisms underlying the cytotoxic activity of SubA in the absence of SubB remained unclear. In the present study, the cytotoxic effects mediated by SubA alone were investigated in more detail in HeLa cells and the human colon cancer cell line HCT116. We found that in the absence of SubB, SubA (10 µg/ml) is internalized into the endoplasmic reticulum (ER), where it cleaves the chaperone GRP78, an already known substrate for SubA after its canonical uptake into cells via SubB. The autonomous cellular uptake of SubA and subsequent cleavage of GRP78 in cells is prevented by treatment of cells with 10 µM brefeldin A, which inhibits the transport of protein toxins into the ER. In addition, by analyzing the SubA mutant SubAΔC344, we identified the C-terminal SEEL motif as an ER-targeting signal. Conclusively, our results strongly suggest that SubA alone shares the same intracellular transport route and cytotoxic activity as the SubAB holotoxin.
Ileo-colic intra-corporeal anastomosis during robotic right colectomy: a systematic literature review and meta-analysis of different techniques
Authors: Guadagni Simone , Palmeri Matteo , Bianchini Matteo , Gianardi Desirée , Furbetta Niccolò , Minichilli Fabrizio , Di Franco Gregorio , Comandatore Annalisa , Di Candio Giulio , Morelli Luca 
Published: January 2021

Abstract
Purpose
Robotic assistance could increase the rate of ileo-colic intra-corporeal anastomosis (ICA) during robotic right colectomy (RRC). However, although robotic ICA can be accomplished with several different technical variants, it is not clear whether some of these technical details should be preferred. An evaluation of the possible advantage of one respect to another would be useful.

Methods
We conducted a systematic review of literature on technical details of robotic ileo-colic ICA, from which we performed a meta-analysis of clinical outcomes. The extracted data allowed a comparative analysis regarding the outcome of overall complication (OC), bleeding rate (BR) and leakage rate (LR), between (1) mechanical anastomosis with robotic stapler, versus laparoscopic stapler, versus totally hand-sewn anastomosis and (2) closure of enterocolotomy with manual double layer, versus single layer, versus stapled.

Results
A total of 30 studies including 2066 patients were selected. Globally, the side-to-side, isoperistaltic anastomosis, realized with laparoscopic staplers, and double-layer closure for enterocolotomy, is the most common technique used. According to the meta-analysis, the use of robotic stapler was significantly associated with a reduction of the BR with respect to mechanical anastomosis with laparoscopic stapler or totally hand-sewn anastomosis. None of the other technical aspects significantly influenced the outcomes.

Conclusions
ICA fashioning during RRC can be accomplished with several technical variants without evidence of a clear superiority of anyone of these techniques. Although the use of robotic staplers could be associated with some benefits, further studies are necessary to draw conclusions.
The calcium-activated chloride channel-associated protein rCLCA2 is expressed throughout rat epidermis, facilitates apoptosis and is downmodulated by UVB
Authors: Hämäläinen L. , Bart G. , Takabe P. , Rauhala L. , Deen A. , Pasonen-Seppänen S. , Kärkkäinen E. , Kärnä R. , Kumlin T. , Tammi M. I. , Tammi R. H. 
Published: January 2021

AbstractThe rodent chloride channel regulatory proteins mCLCA2 and its porcine and human homologues pCLCA2 and hCLCA2 are expressed in keratinocytes but their localization and significance in the epidermis have remained elusive. hCLCA2 regulates cancer cell migration, invasion and apoptosis, and its loss predicts poor prognosis in many tumors. Here, we studied the influences of epidermal maturation and UV-irradiation (UVR) on rCLCA2 (previous rCLCA5) expression in cultured rat epidermal keratinocytes (REK) and correlated the results with mCLCA2 expression in mouse skin in vivo. Furthermore, we explored the influence of rCLCA2 silencing on UVR-induced apoptosis. rClca2 mRNA was strongly expressed in REK cells, and its level in organotypic cultures remained unchanged during the epidermal maturation process from a single cell layer to fully differentiated, stratified cultures. Immunostaining confirmed its uniform localization throughout the epidermal layers in REK cultures and in rat skin. A single dose of UVR modestly downregulated rClca2 expression in organotypic REK cultures. The immunohistochemical staining showed that CLCA2 localized in basal and spinous layers also in mouse skin, and repeated UVR induced its partial loss. Interestingly, silencing of rCLCA2 reduced the number of apoptotic cells induced by UVR, suggesting that by facilitating apoptosis, CLCA2 may protect keratinocytes against the risk of malignancy posed by UVB-induced corrupt DNA.
Modulation of odour-guided behaviour in mosquitoes
Authors: Hill Sharon R. , Ignell Rickard 
Published: January 2021

AbstractMosquitoes are emerging as model systems with which to study innate behaviours through neuroethology and functional genomics. Decades of work on these disease vectors have provided a solid behavioural framework describing the distinct repertoire of predominantly odour-mediated behaviours of female mosquitoes, and their dependence on life stage (intrinsic factors) and environmental cues (extrinsic factors). The purpose of this review is to provide an overview of how intrinsic factors, including adult maturation, age, nutritional status, and infection, affect the attraction to plants and feeding on plant fluids, host seeking, blood feeding, supplemental feeding behaviours, pre-oviposition behaviour, and oviposition in female mosquitoes. With the technological advancements in the recent two decades, we have gained a better understanding of which volatile organic compounds are used by mosquitoes to recognise and discriminate among various fitness-enhancing resources, and characterised their neural and molecular correlates. In this review, we present the state of the art of the peripheral olfactory system as described by the neural physiology, functional genomics, and genetics underlying the demonstrated changes in the behavioural repertoire in female mosquitoes. The review is meant as a summary introduction to the current conceptual thinking in the field.
Odor processing in the cockroach antennal lobe—the network components
Authors: Fuscà Debora , Kloppenburg Peter 
Published: January 2021

AbstractHighly interconnected neural networks perform olfactory signal processing in the central nervous system. In insects, the first synaptic processing of the olfactory input from the antennae occurs in the antennal lobe, the functional equivalent of the olfactory bulb in vertebrates. Key components of the olfactory network in the antennal lobe are two main types of neurons: the local interneurons and the projection (output) neurons. Both neuron types have different physiological tasks during olfactory processing, which accordingly require specialized functional phenotypes. This review gives an overview of important cell type-specific functional properties of the different types of projection neurons and local interneurons in the antennal lobe of the cockroachPeriplaneta americana, which is an experimental system that has elucidated many important biophysical and cellular bases of intrinsic physiological properties of these neurons.
Coeliac disease is associated with depression in children and young adults with type 1 diabetes: results from a multicentre diabetes registry
Authors:   For the DPV Initiative, Tittel Sascha René , Dunstheimer Désirée , Hilgard Dörte , Knauth Burkhild , Fröhlich-Reiterer Elke , Galler Angela , Wurm Michael , Holl Reinhard Walter 
Published: January 2021

Abstract
Aims
To analyse the association between coeliac disease (CD) and depression in children, adolescents, and young adults with type 1 diabetes (T1D).

Methods
We included 79,067 T1D patients aged 6–20 years, with at least six months of diabetes duration, and treatment data between 1995 and 2019 were documented in the diabetes patient follow-up registry. We categorized patients into four groups: T1D only (n = 73,699), T1 + CD (n = 3379), T1D + depression (n = 1877), or T1D + CD + depression (n = 112).

Results
CD and depression were significantly associated (adjusted OR: 1.25 [1.03–1.53]). Females were more frequent in both the depression and the CD group compared with the T1D only group. Insulin pumps were used more frequently in T1D + CD and T1D + depression compared with T1D only (both p < .001). HbA1c was higher in T1D + depression (9.0% [8.9–9.0]), T1D + CD + depression (8.9% [8.6–9.2]), both compared with T1D only (8.2% [8.2–8.2], all p < .001). We found comorbid autism, attention deficit hyperactivity disorder, anxiety, schizophrenia, and eating disorders more frequently in the T1D + CD + depression group compared with T1D only (all p < .001).

Conclusions
CD and depression are associated in young T1D patients. The double load of T1D and CD may lead to an increased risk for depression. Depression was associated with additional psychological and neurological comorbidities. Aside from imperative CD screening after T1D diagnosis and regular intervals, depression screening might be helpful in routine care, especially in patients with diagnosed CD.
Chronic Naltrexone Therapy Is Associated with Improved Cardiac Function in Volume Overloaded Rats
Authors: Dehe Lukas , Shaqura Mohammed , Nordine Michael , Habazettl Helmut , von Kwiatkowski Petra , Schluchter Helena , Shakibaei Mehdi , Mousa Shaaban A. , Schäfer Michael , Treskatsch Sascha 
Published: January 2021

Abstract
Purpose
Myocardial opioid receptors were demonstrated in animals and humans and seem to colocalize with membranous and sarcolemmal calcium channels of the excitation–contraction coupling in the left ventricle (LV). Therefore, this study investigated whether blockade of the cardiac opioid system by naltrexone would affect cardiac function and neurohumoral parameters in Wistar rats with volume overload-induced heart failure.

Methods
Volume overload in Wistar rats was induced by an aortocaval fistula (ACF). Left ventricular cardiac opioid receptors were identified by immunohistochemistry and their messenger ribonucleic acid (mRNA) as well as their endogenous ligand mRNA quantified by real-time polymerase chain reaction (RT-PCR). Following continuous delivery of either the opioid receptor antagonist naltrexone or vehicle via minipumps (n = 5 rats each), hemodynamic and humoral parameters were assessed 28 days after ACF induction. Sham-operated animals served as controls.

Results
In ACF rats mu-, delta-, and kappa-opioid receptors colocalized with voltage-gated L-type Ca2+ channels in left ventricular cardiomyocytes. Chronic naltrexone treatment of ACF rats reduced central venous pressure (CVP) and left ventricular end-diastolic pressure (LVEDP), and improved systolic and diastolic left ventricular functions. Concomitantly, rat brain natriuretic peptide (rBNP-45) and angiotensin-2 plasma concentrations which were elevated during ACF were significantly diminished following naltrexone treatment. In parallel, chronic naltrexone significantly reduced mu-, delta-, and kappa-opioid receptor mRNA, while it increased the endogenous opioid peptide mRNA compared to controls.

Conclusion
Opioid receptor blockade by naltrexone leads to improved LV function and decreases in rBNP-45 and angiotensin-2 plasma levels. In parallel, naltrexone resulted in opioid receptor mRNA downregulation and an elevated intrinsic tone of endogenous opioid peptides possibly reflecting a potentially cardiodepressant effect of the cardiac opioid system during volume overload.
Epistemic evaluation and the need for ‘impure’ epistemic standards
Authors: Kompa Nikola Anna 
Published: January 2021

AbstractThat knowledge ascriptions exhibit some form of sensitivity to context is uncontroversial. How best to account for the context-sensitivity at issue, however, is the topic of heated debates. A certain version of nonindexical contextualism seems to be a promising option. Even so, it is incumbent upon any contextualist account to explain in what way and to what extent the epistemic standard operative in a particular context of epistemic evaluation is affected by non-epistemic factors (such as practical interests). In this paper, I investigate how non-epistemic factors come into play when knowledge is ascribed. I argue that knowledge ascriptions often serve the purpose of providing actionable information. This, in turn, requires that epistemic interests be balanced against non-epistemic interests. Moreover, it raises the question of whose interests matter, those of the ascriber, the addressee (of the knowledge ascription), or the subject of ascription. Eventually, an answer to the question is suggested.