bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design and Delivery of SINEUP: A New Modular Tool to Increase Protein Translation
Authors: Arnoldi Michele , Zarantonello Giulia , Espinoza Stefano , Gustincich Stefano , Di Leva Francesca , Biagioli Marta 
Published: February 2022

AbstractSINEUP is a new class of long non-coding RNAs (lncRNAs) which contain an inverted Short Interspersed Nuclear Element (SINE) B2 element (invSINEB2) necessary to specifically upregulate target gene translation. Originally identified in the mouseAS-Uchl1 (antisense Ubiquitin carboxyl-terminal esterase L1) locus, natural SINEUP molecules are oriented head to head to their sense protein coding, target gene (Uchl1, in this example). Peculiarly, SINEUP is able to augment, in a specific and controlled way, the expression of the target protein, with no alteration of target mRNA levels. SINEUP is characterized by a modular structure with the Binding Domain (BD) providing specificity to the target transcript and an effector domain (ED)—containing the invSINEB2 element—able to promote the loading to the heavy polysomes of the target mRNA. Since the understanding of its modular structure in the endogenous AS-Uchl1 ncRNA, synthetic SINEUP molecules have been developed by creating a specific BD for the gene of interest and placing it upstream the invSINEB2 ED. Synthetic SINEUP is thus a novel molecular tool that potentially may be used for any industrial or biomedical application to enhance protein production, also as possible therapeutic strategy in haploinsufficiency-driven disorders.Here, we describe a detailed protocol to (1) design a specific BD directed to a gene of interest and (2) assemble and clone it with the ED to obtain a functional SINEUP molecule. Then, we provide guidelines to efficiently deliver SINEUP into mammalian cells and evaluate its ability to effectively upregulate target protein translation.
Conjugation of Nucleic Acids and Drugs to Gold Nanoparticles
Authors: Milán-Rois Paula , Rodriguez-Diaz Ciro , Castellanos Milagros , Somoza Álvaro 
Published: February 2022

AbstractGold nanoparticles (AuNPs) can be used as carriers for biomolecules or drugs in cell culture and animal models. Particularly, AuNPs ease their internalization into the cell and prevent their degradation. In addition, engineered AuNPs can be employed as sensors of a variety of biomarkers, where the electronic and optical properties of the AuNPs are exploited for a convenient, easy, and fast read out. However, in all these applications, a key step requires the conjugation of the different molecules to the nanoparticles. The most common approach exploits the great affinity of sulfur for gold. Herein, we summarize the methods used by our group for the conjugation of different molecules with AuNPs. The procedure is easy and takes around 2 days, where the reagents are slowly added, following an incubation at room temperature to ensure the complete conjugation. Finally, the unbound material is removed by centrifugation.
Combatting Conspiratorial Thinking with Controlled Argumentation Dialogue Environments
Authors: Fields Lindsay , Licato John 
Published: February 2022

AbstractThe COVID-19 pandemic has been associated with an explosion in misinformation, leading to increased interest in methods to combat the failures in critical thinking which make such misinformation so powerful. In combatting misinformation, simply throwing uncontrolled argumentation at the problem is often counter-productive, partially because the means by which people evaluate arguments are highly subject to cognitive biases. Such biases which promote jumping to unwarranted conclusions have been shown to correlate with conspiratorial belief. We consider the use of Controlled Argumentation Dialogue Environments (CADEs) as a means to mitigate cognitive biases which contribute to belief in COVID-19 conspiracy theories. We will discuss Warrant Game (WG) and Warrant Game for Analogies (WG-A), CADEs in which two arguers are presented with a divisive issue and two competing positions on that issue. They then compete by iteratively improving warrants for their arguments and attacking those of their opponents. The warrant, when made explicit, makes it easier to determine key features typically associated with argument strength and may reveal hidden assumptions or fundamental reasoning incompatibilities. By presenting an issue and positions which relate to conspiratorial thinking, CADEs may operate as an educational tool for breaking conspiratorial belief into core values and building cognitive skills.
The Vortex—A Journey into Beauty and Mystery
Authors: Decher Reiner 
Published: February 2022

AbstractVorticity is everywhere. We cannot live without it and we cannot fly without it. The vortex as a construct of fluid motion is necessary for the wing to lift. The propulsion system, be it a propeller or a jet engine, also needs a vorticity to provide the force needed to overcome the resistance of motion through air. This chapter is a road map of how we will proceed on a journey of exploration that will take us from abstract ideas to the observation of beauty and the realization of great flight performance.
Emergent strings from infinite distance limits
Authors: Lee Seung-Joo , Lerche Wolfgang , Weigand Timo 
Published: February 2022

Abstract
As a refinement of the Swampland Distance Conjecture, we propose that a quantum gravitational theory in an infinite distance limit of its moduli space either decompactifies, or reduces to an asymptotically tensionless, weakly coupled string theory. We support our claim by classifying, as special cases, the behaviour of M-Theory and Type IIA string theory compactifications on Calabi-Yau three-folds at infinite distances in Kähler moduli space.The analysis comprises three parts: we first classify the possible infinite distance limits in the classical Kähler moduli space of a Calabi-Yau three-fold. Each such limit at finite volume is characterized by a universal fibration structure, for which the generic fiber shrinking in the limit is either an elliptic curve, a K3 surface, or an Abelian surface.In the second part we focus on M-Theory and investigate the nature of the towers of asymptotically massless states that arise from branes wrapped on the shrinking fibers. Depending on which of the three classes of fibrations are considered, we obtain decompactification to F-Theory, or a theory with a unique asymptotically tensionless, weakly coupled heterotic or Type II string, respectively. The latter probes a dual D-manifold which is in general non-geometric. In addition to the intrinsic string excitations, towers of states from M2-branes along non-contractible curves become light and correspond to further wrapping and winding modes of the tensionless heterotic or Type II string.In the third part of the analysis, we consider Type IIA string theory on Calabi-Yau three-folds and show that quantum effects obstruct taking finite volume infinite distance limits in the Kähler moduli space. The only possible infinite distance limit which is not a decompactification limit involves K3-fibrations with string scale fiber volume and gives rise to an emergent tensionless heterotic string.
CD73 controls ocular adenosine levels and protects retina from light-induced phototoxicity
Authors: Losenkova Karolina , Takeda Akira , Ragauskas Symantas , Cerrada-Gimenez Marc , Vähätupa Maria , Kaja Simon , Paul Marius L. , Schmies Constanze C. , Rolshoven Georg , Müller Christa E. , Sandholm Jouko , Jalkanen Sirpa , Kalesnykas Giedrius , Yegutkin Gennady G. 
Published: February 2022

AbstractATP and adenosine have emerged as important signaling molecules involved in vascular remodeling, retinal functioning and neurovascular coupling in the mammalian eye. However, little is known about the regulatory mechanisms of purinergic signaling in the eye. Here, we used three-dimensional multiplexed imaging, in situ enzyme histochemistry, flow cytometric analysis, and single cell transcriptomics to characterize the whole pattern of purine metabolism in mouse and human eyes. This study identified ecto-nucleoside triphosphate diphosphohydrolase-1 (NTPDase1/CD39), NTPDase2, and ecto-5′-nucleotidase/CD73 as major ocular ecto-nucleotidases, which are selectively expressed in the photoreceptor layer (CD73), optic nerve head, retinal vasculature and microglia (CD39), as well as in neuronal processes and cornea (CD39, NTPDase2). Specifically, microglial cells can create a spatially arranged network in the retinal parenchyma by extending and retracting their branched CD39high/CD73low processes and forming local “purinergic junctions” with CD39low/CD73− neuronal cell bodies and CD39high/CD73− retinal blood vessels. The relevance of the CD73–adenosine pathway was confirmed by flash electroretinography showing that pharmacological inhibition of adenosine production by injection of highly selective CD73 inhibitor PSB-12489 in the vitreous cavity of dark-adapted mouse eyes rendered the animals hypersensitive to prolonged bright light, manifested as decreased a-wave and b-wave amplitudes. The impaired electrical responses of retinal cells in PSB-12489-treated mice were not accompanied by decrease in total thickness of the retina or death of photoreceptors and retinal ganglion cells. Our study thus defines ocular adenosine metabolism as a complex and spatially integrated network and further characterizes the critical role of CD73 in maintaining the functional activity of retinal cells.
PACS2–TRPV1 axis is required for ER–mitochondrial tethering during ER stress and lung fibrosis
Authors: Knoell Jessica , Chillappagari Shashi , Knudsen Lars , Korfei Martina , Dartsch Ruth , Jonigk Danny , Kuehnel Mark P. , Hoetzenecker Konrad , Guenther Andreas , Mahavadi Poornima 
Published: February 2022

AbstractEndoplasmic reticulum (ER) and mitochondria (mito) play a vital role in alveolar type II cell (AEC2) homeostasis and are both stressed in patients with idiopathic pulmonary fibrosis (IPF). Up to now, no data are available with regard to ER–mito cross talk and tethering under conditions of IPF. We here demonstrate that ER–mitochondrial tethering is reduced upon experimental ER stress in vitro and in the IPF AECII ex vivo, and this is—at least in part—due to decreased phosphofurin acidic cluster sorting protein 2 (PACS-2, also called PACS2) protein levels. PACS2 levels are influenced by its interaction with the transient receptor potential cation channel subfamily V member 1 (TRPV1) and can be experimentally modified by the TRPV1-modulating drug capsaicin (CPS). Employing alveolar epithelial cells with overexpression of the terminal ER stress signaling factor Chop or the IPF-associated surfactant protein C mutation (SPCΔexon4) in vitro, we observed a restoration of PACS2 levels upon treatment with CPS. Similarly, treatment of precision cut lung slices from IPF patients with CPS ex vivo forwarded similar effects. Importantly, in all models such kind of intervention also greatly reduced the extent of alveolar epithelial apoptosis. We therefore conclude that therapeutic targeting of the PACS2–TRPV1 axis represents an interesting novel, epithelial-protective approach in IPF.
Thermodynamic theory of dislocation/grain boundary interaction
Authors: Piao Yinguang , Le Khanh Chau 
Published: February 2022

AbstractThe thermodynamic theory of dislocation/grain boundary interaction, including dislocation pileup against, absorption by, and transfer through the grain boundary, is developed for non-uniform plastic deformations in polycrystals. The case study is carried out on the boundary conditions affecting work hardening of a bicrystal subjected to plane constrained shear for three types of grain boundaries: (i) impermeable hard grain boundary, (ii) grain boundary that allows dislocation transfer without absorption, and (iii) grain boundary that absorbs dislocations and allows them to pass later.
Assessment of Activity Profiles in Older Adults and Lower Limb Bone Parameters: Observations from the Hertfordshire Cohort Study
Authors: Parsons C. M. , Dennison E. M. , Fuggle N. , Breasail M. Ó. , Deere K. , Hannam K. , Tobias J. H. , Cooper C. , Ward K. A. 
Published: February 2022

AbstractAs muscle strength and function decline with age the optimal high-impact physical activity (PA) required for bone remodelling is rarely achievable in older adults. This study aimed to explore the activity profiles of community-dwelling older men and women and to assess the relationship between individual PA profiles and lower limb bone parameters. Participants from the Hertfordshire Cohort Study wore triaxial accelerometers for 7 days and counts of low (0.5–1.0 g), medium (1.0–1.5 g), and high (> 1.5 g) vertical-impact activity were calculated. Two years later, participants underwent a pQCT scan of the tibia (4% and 38% sites) to obtain measures of bone mineral density and bone geometry. Linear regression was used to quantify associations between bone and PA loading profiles adjusting for age, sex, loading category, and BMI. Results are presented as β [95% confidence interval]. Bone and PA data were available for 82 participants. The mean (SD) age at follow-up was 81.4(2.7) years, 41.5% (n = 34) were women. The median low-impact PA count was 5281 (Inter-quartile range (IQR) 2516–12,977), compared with a median of only 189 (IQR 54–593) in medium, and 39 (IQR 9–105) in high-impact counts. Positive associations between high-impact PA and cortical area (mm2), polar SSI (mm3), and total area (mm2) at the 38% slice (6.21 [0.88, 11.54]; 61.94 [25.73, 98.14]; 10.09 [3.18, 16.99], respectively). No significant associations were found at distal tibia. These data suggest that maintaining high (> 1.5 g)-impact activity is difficult for older adults to achieve; however, even small amounts of high-impact PA are positively associated with selected cortical bone parameters 2 years later.
Peroral Endoscopic Myotomy for Achalasia
Authors: Ujiki Michael B. , VanDruff Vanessa N. 
Published: February 2022

AbstractBackgroundPeroral endoscopic myotomy (POEM) utilizes the principles of natural orifice transluminal surgery to create an operative tunnel within the submucosal space, perform an endoluminal esophagogastromyotomy, and ultimately mitigate the progressive symptoms of achalasia. POEM is an innovative minimally invasive technique increasing in popularity and clinical significance as an effective treatment for achalasia and other disorders of spastic esophageal motility.MethodsA comprehensive literature review was performed regarding the procedure, outcomes, and technical advancements in POEM.ResultsA growing number of studies world‐wide have shown that POEM is a safe and effective for all types of achalasia, sigmoid and non‐sigmoid type.ConclusionsPOEM continues to gain traction as a highly effective therapeutic modality for achalasia. As natural orifice transluminal surgery advances, further research is necessary to optimize utilization of endoluminal functional imaging, to tailor endoscopic technique, and to address the adverse effect of post‐operative reflux and esophagitis.
Dear Doctor Letters regarding citalopram and escitalopram: guidelines vs real-world data
Authors: de Bardeci Mateo , Greil Waldemar , Stassen Hans , Willms Jamila , Köberle Ursula , Bridler René , Hasler Gregor , Kasper Siegfried , Rüther Eckart , Bleich Stefan , Toto Sermin , Grohmann Renate , Seifert Johanna 
Published: February 2022

AbstractDear Doctor Letters (DDLs, Direct Healthcare Professional Communications) from 2011 provided guidance regarding QTc-prolonging effects with risk of torsade de pointes during treatment with citalopram and escitalopram. This study examines the DDLs’ effects on prescription behavior. Data from 8842 inpatients treated with citalopram or escitalopram with a primary diagnosis of major depressive disorder (MDD) were derived from a European pharmacovigilance study (Arzneimittelsicherheit in der Psychiatrie, AMSP) from 2001 to 2017. It was examined to what extent new maximum doses were adhered to and newly contraindicated combinations with QTc-prolonging drugs were avoided. In addition, the prescriptions of psychotropic drugs before and after DDLs were compared in all 43,480 inpatients with MDD in the data set. The proportion of patients dosed above the new limit decreased from 8 to 1% in patients ≤ 65 years and from 46 to 23% in patients > 65 years old for citalopram versus 14–5% and 47–31% for escitalopram. Combinations of es-/citalopram with other QTc-prolonging psychotropic drugs reduced only insignificantly (from 35.9 to 30.9%). However, the proportion of patients with doses of quetiapine > 150 mg/day substantially decreased within the combinations of quetiapine and es-/citalopram (from 53 to 35%). After the DDLs, prescription of citalopram decreased and of sertraline increased. The DDLs’ recommendations were not entirely adhered to, particularly in the elderly and concerning combination treatments. This might partly be due to therapeutic requirements of the included population. Official warnings should consider clinical needs.
CD13 is a useful tool in the differential diagnosis of meningiomas with potential biological and prognostic implications
Authors: Marletta Stefano , Luchini Claudio , Sperandio Nicola , Torresani Evelin , Sorio Alessandro , Girolami Ilaria , Scarpa Aldo , Eccher Albino , Ghimenton Claudio 
Published: February 2022

AbstractMeningiomas are common tumors of the central nervous system. Although their histological diagnosis is usually straightforward, their differential diagnosis versus other tumors may be challenging at times. The objective of this study is to assess the diagnostic value of CD13 immunoexpression in the differential diagnosis between meningiomas and their morphological mimics. Immunohistochemical analysis for CD13, epithelial membrane antigen, SOX10, and STAT6 was carried out in a large cohort of primary meningeal tumors comprising 225 meningiomas, 15 schwannomas, and 20 solitary fibrous tumor/hemangiopericytomas. Within the meningioma group, the expression of CD13 and epithelial membrane antigen was distinguished in three categories using a semiquantitative score. Most of meningiomas expressed CD13 (94%) and epithelial membrane antigen (96%) while none of the schwannomas nor of the solitary fibrous tumor/hemangiopericytomas was positive for either the two markers. Diffuse positivity for CD13 and epithelial membrane antigen was more common in low-grade meningiomas than in anaplastic ones, which were also more often negative for such markers, especially for CD13 (32%). CD13 is a helpful immunohistochemical marker for the differential diagnosis of meningiomas and their mimics, achieving in combination with epithelial membrane antigen maximal sensitivity (100%) and showing statistically relevant difference of expression in comparison with both schwannomas (p < 0.0001) and solitary fibrous tumor/hemangiopericytomas (p < 0.0001). Furthermore, loss of CD13 expression could be related to outcome as it is associated with worrisome histological findings, mainly in the setting of anaplastic meningiomas.
Identifying Dysphagia and Demographic Associations in Older Adults Using Electronic Health Records: A National Longitudinal Observational Study in Wales (United Kingdom) 2008–2018
Authors: Hollinghurst Joe , Smithard David G. 
Published: February 2022

AbstractDysphagia is increasingly being recognised as a geriatric syndrome (giant). There is limited research on the prevalence of dysphagia using electronic health records. To investigate associations between dysphagia, as recorded in electronic health records and age, frailty using the electronic frailty index, gender and deprivation (Welsh index of multiple deprivation). A Cross-sectional longitudinal cohort study in over 400,000 older adults was undertaken (65 +) in Wales (United Kingdom) per year from 2008 to 2018. We used the secure anonymised information linkage databank to identify dysphagia diagnoses in primary and secondary care. We used chi-squared tests and multivariate logistic regression to investigate associations between dysphagia diagnosis and age, frailty (using the electronic Frailty index), gender and deprivation. Data indicated < 1% of individuals were recorded as having a dysphagia diagnosis per year. We found dysphagia to be statistically significantly associated with older age, more severe frailty and individuals from more deprived areas. Multivariate analyses indicated increased odds ratios [OR (95% confidence intervals)] for a dysphagia diagnosis with increased age [reference 65–74: aged 75–84 OR 1.09 (1.07, 1.12), 85 + OR 1.23 (1.20, 1.27)], frailty (reference fit: mild frailty 2.45 (2.38, 2.53), moderate frailty 4.64 (4.49, 4.79) and severe frailty 7.87 (7.55, 8.21)] and individuals from most deprived areas [reference 5. Least deprived, 1. Most deprived: 1.10 (1.06, 1.14)]. The study has identified that prevalence of diagnosed dysphagia is lower than previously reported. This study has confirmed the association of dysphagia with increasing age and frailty. A previously unreported association with deprivation has been identified. Deprivation is a multifactorial problem that is known to affect health outcomes, and the association with dysphagia should not be a surprise. Research in to this relationship is indicated.
The use of fluorescence angiography to assess bowel viability in the acute setting: an international, multi-centre case series
Authors: Joosten Johanna J. , Longchamp Grégoire , Khan Mohammad F. , Lameris Wytze , van Berge Henegouwen Mark I. , Bemelman Wilhelmus A. , Cahill Ronan A. , Hompes Roel , Ris Frédéric 
Published: February 2022

Abstract
Introduction
Assessing bowel viability can be challenging during acute surgical procedures, especially regarding mesenteric ischaemia. Intraoperative fluorescence angiography (FA) may be a valuable tool for the surgeon to determine whether bowel resection is necessary and to define the most appropriate resection margins. The aim of this study is to report on FA use in the acute setting and to judge its impact on intraoperative decision making.

Materials and methods
This is a multi-centre, retrospective case series of patients undergoing emergency abdominal surgery between February 2016 and 2021 in three general/colorectal units where intraoperative FA was performed to assess bowel viability. Primary endpoint was change of management after the FA assessment.

Results
A total of 93 patients (50 males, 66.6 ± 19.2 years, ASA score ≥ III in 85%) were identified and studied. Initial surgical approach was laparotomy in 66 (71%) patients and laparoscopy in 27 (29% and seven, 26% conversions). The most common aetiologies were mesenteric ischaemia (n = 42, 45%) and adhesional/herniae-related strangulation (n = 41, 44%). In 50 patients a bowel resection was performed. Overall rates of anastomosis after resection, reoperation and 30-day mortality were 48% (n = 24/50, one leak), 12% and 18%, respectively. FA changed management in 27 (29%) patients. In four patients (4% overall), resection was avoided and in 21 (23%) extra bowel length was preserved (median 50 cm of bowel saved, IQR 28–98) although three patients developed further ischaemia. FA prompted extended resection (median of 20 cm, IQR 10–50 extra bowel) in six (6%) patients.

Conclusion
Intraoperative use of FA impacts surgical decisions regarding bowel resection for intestinal ischaemia, potentially enabling bowel preservation in approximately one out of four patients. Prospective studies are needed to optimize the best use of this technology for this indication and to determine standards for the interpretation of FA images and the potential subsequent need for second-look surgeries.