bluuebunny/crossref_metadata_2025 huggingface dataset:
Established and emerging treatments for diabetes-associated lower urinary tract dysfunction
Authors: Erdogan Betül R. , Liu Guiming , Arioglu-Inan Ebru , Michel Martin C.
Published: May 2022

Dysfunction of the lower urinary tract (LUT) including urinary bladder and urethra (and prostate in men) is one of the most frequent complications of diabetes and can manifest as overactive bladder, underactive bladder, urinary incontinence, and as aggravated symptoms of benign prostate hyperplasia. We have performed a selective literature search to review existing evidence on efficacy of classic medications for the treatment of LUT dysfunction in diabetic patients and animals, i.e., α1-adrenoceptor and muscarinic receptor antagonists, β3-adrenoceptor agonists, and phosphodiesterase type 5 inhibitors. Generally, these agents appear to have comparable efficacy in patients and/or animals with and without diabetes. We also review effects of antidiabetic medications on LUT function. Such studies have largely been performed in animal models. In the streptozotocin-induced models of type 1 diabetes, insulin can prevent and reverse alterations of morphology, function, and gene expression patterns in bladder and prostate. Typical medications for the treatment of type 2 diabetes have been studied less often, and the reported findings are not yet sufficient to derive robust conclusions. Thereafter, we review animal studies with emerging medications perhaps targeting diabetes-associated LUT dysfunction. Data with myoinositol, daidzein, and with compounds that target oxidative stress, inflammation, Rac1, nerve growth factor, angiotensin II receptor, serotonin receptor, adenosine receptor, and soluble guanylyl cyclase are not conclusive yet, but some hold promise as potential treatments. Finally, we review nonpharmacological interventions in diabetic bladder dysfunction. These approaches are relatively new and give promising results in preclinical studies. In conclusion, the insulin data in rodent models of type 1 diabetes suggest that diabetes-associated LUT function can be mostly or partially reversed. However, we propose that considerable additional experimental and clinical studies are needed to target diabetes itself or pathophysiological changes induced by chronic hyperglycemia for the treatment of diabetic uropathy.
Blobbed Topological Recursion of the Quartic Kontsevich Model I: Loop Equations and Conjectures
Authors: Branahl Johannes , Hock Alexander , Wulkenhaar Raimar
Published: May 2022

We provide strong evidence for the conjecture that the analogue of Kontsevich’s matrix Airy function, with the cubic potential $$\mathrm {Tr}(\Phi ^3)$$

Tr
(

Φ
3

)

replaced by a quartic term $$\mathrm {Tr}(\Phi ^4)$$

Tr
(

Φ
4

)

, obeys the blobbed topological recursion of Borot and Shadrin. We identify in the quartic Kontsevich model three families of correlation functions for which we establish interwoven loop equations. One family consists of symmetric meromorphic differential forms $$\omega _{g,n}$$

ω

g
,
n

labelled by genus and number of marked points of a complex curve. We reduce the solution of all loop equations to a straightforward but lengthy evaluation of residues. In all evaluated cases, the $$\omega _{g,n}$$

ω

g
,
n

consist of a part with poles at ramification points which satisfies the universal formula of topological recursion, and of a part holomorphic at ramification points for which we provide an explicit residue formula.
Having several options does not increase the time it takes to make a movement to an adequate end point
Authors: Brenner Eli , Smeets Jeroen B. J.
Published: May 2022

Throughout the day, people constantly make choices such as where to direct their gaze or place their foot. When making such movement choices, there are usually multiple acceptable options, although some are more advantageous than others. How much time does it take to make such choices and to what extent is the most advantageous option chosen from the available alternatives? To find out, we asked participants to collect points by tapping on any of several targets with their index finger. It did not take participants more time to direct their movements to an advantageous target when there were more options. Participants chose targets that were advantageous because they were easier to reach. Targets could be easier to reach because the finger was already moving in their direction when they appeared, or because they were larger or oriented along the movement direction so that the finger could move faster towards them without missing them. When the target’s colour indicated that it was worth more points they chose it slightly less fast, presumably because it generally takes longer to respond to colour than to respond to attributes such as size. They also chose it less often than they probably should have, presumably because the advantage of choosing it was established arbitrarily. We conclude that having many options does not increase the time it takes to move to an adequate target.
Experimental Evidence for Manure-Borne Bacteria Invasion in Soil During a Coalescent Event: Influence of the Antibiotic Sulfamethazine
Authors: Billet Loren , Pesce Stéphane , Martin-Laurent Fabrice , Devers-Lamrani Marion
Published: May 2022

The fertilization of agricultural soil by organic amendment that may contain antibiotics, like manure, can transfer bacterial pathogens and antibiotic-resistant bacteria to soil communities. However, the invasion by manure-borne bacteria in amended soil remains poorly understood. We hypothesized that this kind of process is both influenced by the soil properties (and those of its microbial communities) and by the presence of contaminants such as antibiotics used in veterinary care. To test that, we performed a microcosm experiment in which four different soils were amended or not with manure at an agronomical dose and exposed or not to the antibiotic sulfamethazine (SMZ). After 1 month of incubation, the diversity, structure, and composition of bacterial communities of the soils were assessed by 16S rDNA sequencing. The invasion of manure-borne bacteria was still perceptible 1 month after the soil amendment. The results obtained with the soil already amended in situ with manure 6 months prior to the experiment suggest that some of the bacterial invaders were established in the community over the long term. Even if differences were observed between soils, the invasion was mainly attributable to some of the most abundant OTUs of manure (mainly Firmicutes). SMZ exposure had a limited influence on soil microorganisms but our results suggest that this kind of contaminant can enhance the invasion ability of some manure-borne invaders.
In vitro dose effect relationships of actinium-225- and lutetium-177-labeled PSMA-I&T
Authors: Ruigrok Eline A. M. , Tamborino Giulia , de Blois Erik , Roobol Stefan J. , Verkaik Nicole , De Saint-Hubert Marijke , Konijnenberg Mark W. , van Weerden Wytske M. , de Jong Marion , Nonnekens Julie
Published: May 2022

Purpose

Targeting the prostate-specific membrane antigen (PSMA) using lutetium-177-labeled PSMA-specific tracers has become a very promising novel therapy option for prostate cancer (PCa). The efficacy of this therapy might be further improved by replacing the β-emitting lutetium-177 with the α-emitting actinium-225. Actinium-225 is thought to have a higher therapeutic efficacy due to the high linear energy transfer (LET) of the emitted α-particles, which can increase the amount and complexity of the therapy induced DNA double strand breaks (DSBs). Here we evaluated the relative biological effectiveness of [225Ac]Ac-PSMA-I&T and [177Lu]Lu-PSMA-I&T by assessing in vitro binding characteristics, dosimetry, and therapeutic efficacy.

Methods and results

The PSMA-expressing PCa cell line PC3-PIP was used for all in vitro assays. First, binding and displacement assays were performed, which revealed similar binding characteristics between [225Ac]Ac-PSMA-I&T and [177Lu]Lu-PSMA-I&T. Next, the assessment of the number of 53BP1 foci, a marker for the number of DNA double strand breaks (DSBs), showed that cells treated with [225Ac]Ac-PSMA-I&T had slower DSB repair kinetics compared to cells treated with [177Lu]Lu-PSMA-I&T. Additionally, clonogenic survival assays showed that specific targeting with [225Ac]Ac-PSMA-I&T and [177Lu]Lu-PSMA-I&T caused a dose-dependent decrease in survival. Lastly, after dosimetric assessment, the relative biological effectiveness (RBE) of [225Ac]Ac-PSMA-I&T was found to be 4.2 times higher compared to [177Lu]Lu-PSMA-I&T.

Conclusion

We found that labeling of PSMA-I&T with lutetium-177 or actinium-225 resulted in similar in vitro binding characteristics, indicating that the distinct biological effects observed in this study are not caused by a difference in uptake of the two tracers. The slower repair kinetics of [225Ac]Ac-PSMA-I&T compared to [177Lu]Lu-PSMA-I&T correlates to the assumption that irradiation with actinium-225 causes more complex, more difficult to repair DSBs compared to lutetium-177 irradiation. Furthermore, the higher RBE of [225Ac]Ac-PSMA-I&T compared to [177Lu]Lu-PSMA-I&T underlines the therapeutic potential for the treatment of PCa.
Enumeration of binary trees compatible with a perfect phylogeny
Authors: Palacios Julia A. , Bhaskar Anand , Disanto Filippo , Rosenberg Noah A.
Published: May 2022

Evolutionary models used for describing molecular sequence variation suppose that at a non-recombining genomic segment, sequences share ancestry that can be represented as a genealogy—a rooted, binary, timed tree, with tips corresponding to individual sequences. Under the infinitely-many-sites mutation model, mutations are randomly superimposed along the branches of the genealogy, so that every mutation occurs at a chromosomal site that has not previously mutated; if a mutation occurs at an interior branch, then all individuals descending from that branch carry the mutation. The implication is that observed patterns of molecular variation from this model impose combinatorial constraints on the hidden state space of genealogies. In particular, observed molecular variation can be represented in the form of a perfect phylogeny, a tree structure that fully encodes the mutational differences among sequences. For a sample of n sequences, a perfect phylogeny might not possess n distinct leaves, and hence might be compatible with many possible binary tree structures that could describe the evolutionary relationships among the n sequences. Here, we investigate enumerative properties of the set of binary ranked and unranked tree shapes that are compatible with a perfect phylogeny, and hence, the binary ranked and unranked tree shapes conditioned on an observed pattern of mutations under the infinitely-many-sites mutation model. We provide a recursive enumeration of these shapes. We consider both perfect phylogenies that can be represented as binary and those that are multifurcating. The results have implications for computational aspects of the statistical inference of evolutionary parameters that underlie sets of molecular sequences.
Indirect CT venography of the lower extremities: impact of scan delay and patient factors on contrast enhancement and examination quality
Authors: Tran Thien Trung , Kristiansen Cathrine Helgestad , Thomas Owen , Roy Sumit , Haidl Felix , Ashraf Haseem , Kløw Nils Einar , Stavem Knut , Lauritzen Peter M.
Published: May 2022

Objectives

Indirect computed tomography venography (CTV) is often the next imaging modality for deep vein thrombosis (DVT) when sonography is inconclusive. Our aim was to investigate the impact of scan delay and patient factors on contrast enhancement (CE) and examination quality in CTV.

Methods

Patients with clinical suspicion or clinical mimics of DVT in one large hospital were enrolled. Age, sex, body weight, height, heart rate, systolic blood pressure and cardiac output were registered. CTV of the popliteal veins was obtained at 30 s intervals at 30–210 s delays. The proportions of examinations with CE exceeding predefined cut-offs were estimated and subjective examination quality was rated. Changes in CE with time, and associations between patient factors and time to peak contrast enhancement (TPCE) were modelled with mixed effects non-linear and linear regression, respectively.

Results

The CE increased with increasing scan delay and reached a plateau from 120 to 210 s. The percentages of examinations achieving enhancement above cut-offs across all thresholds from 70 to 100 HU were higher at 120 s compared to 90 s (p < 0.001). After 120 s, there were no differences across scan delays for any thresholds. No patient factors showed a significant effect on TPCE. The percentage of examinations rated as acceptable was higher at 120 s compared to 90 s (p < 0.001). After 120 s, there were no statistically significant differences across scan delays.

Conclusions

No patient factors were associated with TPCE in CTV. A fixed scan delay of 120–210 s yielded the best examination quality.

Key Points

• Contrast enhancement reached a plateau at scan delay between 90 and 120 s.

• A scan delay of 120–210 s yielded the best examination quality.

• No patient factors were associated with time to peak contrast enhancement.
The evolution of human fatigue resistance
Authors: Marino Frank E. , Sibson Benjamin E. , Lieberman Daniel E.
Published: May 2022

Humans differ from African great apes in numerous respects, but the chief initial difference setting hominins on their unique evolutionary trajectory was habitual bipedalism. The two most widely supported selective forces for this adaptation are increased efficiency of locomotion and improved ability to feed in upright contexts. By 4 million years ago, hominins had evolved the ability to walk long distances but extreme selection for endurance capabilities likely occurred later in the genusHomoto help them forage, power scavenge and persistence hunt in hot, arid conditions. In this review we explore the hypothesis that to be effective long-distance walkers and especially runners, there would also have been a strong selective benefit amongHomoto resist fatigue. Our hypothesis is that since fatigue is an important factor that limits the ability to perform endurance-based activities, fatigue resistance was likely an important target for selection during human evolution for improved endurance capabilities. We review the trade-offs between strength, power, and stamina in apes andHomoand discuss three biological systems that we hypothesize humans evolved adaptations for fatigue resistance: neurological, metabolic and thermoregulatory. We conclude that the evolution of endurance at the cost of strength and power likely also involved the evolution of mechanisms to resist fatigue.
Properties, sensitivity, and stability of the Southern Hemisphere salinity minimum layer in the UKESM1 model
Authors: Meuriot Ophélie , Lique Camille , Plancherel Yves
Published: May 2022

Antarctic Intermediate Water (AAIW) is a water mass originating in the Southern Ocean characterised by its low salinity. The properties of the salinity minimum layer that characterise AAIW in the CMIP6 UKESM1 model and its response to different climate change scenarios are investigated. In UKESM1, the depth of the salinity minimum shoals by 116 m in the SSP5-8.5 run compared to the control run by 2080–2100. The salinity minimum also gets warmer (+ 1.9 °C) and lighter (− 0.4 kg/m3) and surface properties where the salinity minimum outcrops warm, freshen and lighten in all scenarios. In spite of these expected changes in properties, the location where the salinity minimum outcrops does not change in any of the future scenarios. The stability of the outcrop location of the salinity minimum is linked to the relative stability of the position of the Antarctic Circumpolar Current (ACC) in UKESM1. The position of the ACC does not follow the maximum wind stress trend, which intensifies and shifts poleward under radiative forcing. Changes in surface buoyancy fluxes in the region are consistent with the changes in hydrographic properties observed at depth on the salinity minimum mentioned above. However, transformation rates at the density corresponding to the salinity minimum outcrop remain constant in all scenarios. Stability in transformation rates at that density is due to the haline and thermal contributions counteracting one another. This analysis identifies two features (outcrop location, transformation rate) associated with the salinity minimum defining AAIW that show remarkable stability in an otherwise changing world. The effect of model resolution and other parameterisations on these findings have yet to be evaluated.
Convection-permitting simulations of historical and possible future climate over the contiguous United States
Authors: Gensini Vittorio A. , Haberlie Alex M. , Ashley Walker S.
Published: May 2022

This study presents a novel, high-resolution, dynamically downscaled dataset that will help inform regional and local stakeholders regarding potential impacts of climate change at the scales necessary to examine extreme mesoscale conditions. WRF-ARW version 4.1.2 was used in a convection-permitting configuration (horizontal grid spacing of 3.75 km; 51 vertical levels; data output interval of 15-min) as a regional climate model for a domain covering the contiguous US Initial and lateral boundary forcing for the regional climate model originates from a global climate model simulation by NCAR (Community Earth System Model) that participated in phase 5 of the Coupled Model Inter comparison Project. Herein, we use a version of these data that are regridded and bias corrected. Two 15-year downscaled simulation epochs were examined comprising of historical (HIST; 1990–2005) and potential future (FUTR; 2085–2100) climate using Representative Concentration Pathway (RCP) 8.5. HIST verification against independent observational data revealed that annual/seasonal/monthly temperature and precipitation (and their extremes) are replicated admirably in the downscaled HIST epoch, with the largest biases in temperature noted with daily maximum temperatures (too cold) and the largest biases in precipitation (too dry) across the southeast US during the boreal warm season. The simulations herein are improved compared to previous work, which is significant considering the differences in previous modeling approaches. Future projections of temperature under the RCP 8.5 scenario are consistent with previous works using various methods. Future precipitation projections suggest statistically significant decreases of precipitation across large segments of the southern Great Plains and Intermountain West, whereas significant increases were noted in the Tennessee/Ohio Valleys and across portions of the Pacific Northwest. Overall, these simulations serve as an additional datapoint/method to detect potential future changes in extreme meso-γ weather phenomena.
Relationships between sympathetic markers and heart rate thresholds for cardiovascular risk in chronic heart failure
Authors: Grassi Guido , Seravalle Gino , Vanoli Jennifer , Facchetti Rita , Spaziani Domenico , Mancia Giuseppe
Published: May 2022

Background

Results of recent clinical trials have shown that in heart failure (HF) heart rate (HR) values > 70 beats/minute are associated with an increased cardiovascular risk. No information is available on whether the sympathetic nervous system is differently activated in HF patients displaying resting HR values above or below this cutoff.

Methods

In 103 HF patients aged 62.7 ± 0.9 (mean ± SEM) years and in 62 heathy controls of similar age we evaluated muscle sympathetic nerve traffic (MSNA, microneurography) and venous plasma norepinephrine (NE, HPLC assay), subdividing the subjects in different groups according to their resting clinic and 24-h HR values.

Results

In HF progressively greater values of clinic or 24-h HR were associated with a progressive increase in both MSNA and NE. HR cutoff values adopted in large scale clinical trials for determining cardiovascular risk, i.e., 70 beats/minute, were associated with MSNA values significantly greater than the ones detected in patients with lower HR, this being the case also for NE. In HF both MSNA and NE were significantly related to clinic (r = 0.92, P < 0.0001 and r = 0.81, P < 0.0001, respectively) and 24-h (r = 0.91, P < 0.0001 and r = 0.79, P < 0.0001, respectively) HR. The behavior of sympathetic markers described in HF was specific for this clinical condition, being not observed in healthy controls.

Conclusions

Both clinic and 24-h HR values greater than 70 beats/minute are associated with an increased sympathetic activation, which parallels for magnitude the HR elevations. These findings support the relevance of using in the therapeutic approach to HF drugs exerting sympathomoderating properties.

Graphical abstract
EKG-Diagnostik mithilfe künstlicher Intelligenz: aktueller Stand und zukünftige Perspektiven – Teil 1
Authors: Haverkamp Wilhelm , Strodthoff Nils , Israel Carsten
Published: May 2022

Auch wenn die Elektrokardiographie mittlerweile ein über 100 Jahre altes diagnostisches Verfahren ist, kann die Medizin auf sie nicht verzichten. Ganz im Gegenteil, das Interesse am Elektrokardiogramm (EKG) und seine klinische Bedeutung nehmen derzeit sogar wieder zu. Dies hat nicht nur mit einer Fülle von neuen Erkenntnissen zu der elektrokardiographischen Manifestation alter und neuer kardiovaskulärer Pathologien zu tun, sondern auch damit, dass das EKG vermehrt Gegenstand von Analysen ist, die sich künstlicher Intelligenz (KI) bedienen. Die Schwächen, die der klassischen computerassistierten EKG-Auswertung anhaften, erscheinen mithilfe von KI überwindbar. Zudem scheint KI in der Lage zu sein, Informationen aus EKGs zu extrahieren, die weit über das hinausgehen, was ein Mensch leisten kann. Nicht alle Ärzte sind mit der Anwendung dieser neuen Technologie und ihren Teilbereichen, dem Machine Learning (maschinelles Lernen) und insbesondere dem Deep Learning (tiefes Lernen; wenig gebräuchlicher Ausdruck), vertraut. Die Bewertung ihrer aktuellen und zukünftigen klinischen Relevanz fällt schwer. Diese zweiteilige Übersicht beschäftigt sich mit der KI-basierten EKG-Analyse. In Teil 1 erfolgt eine Einführung in grundlegende Aspekte des Vorgehens. Teil 2, der separat publiziert wird, widmet sich dem aktuellen Stand der Forschung und bespricht die Ergebnisse verfügbarer Studien. Zudem werden möglich Szenarien der zukünftigen Anwendung von KI bei der EKG-Analyse diskutiert.
EKG-Diagnostik mit Hilfe künstlicher Intelligenz: aktueller Stand und zukünftige Perspektiven – Teil 2
Authors: Haverkamp Wilhelm , Strodthoff Nils , Israel Carsten
Published: May 2022

Während grundlegende Aspekte der Anwendung von künstlicher Intelligenz (KI) zur Elektrokardiogramm(EKG)-Analyse in Teil 1 dieser Übersicht behandelt wurden, beschäftigt sich die vorliegende Arbeit (Teil 2) mit einer Besprechung von aktuellen Studien zum praktischen Einsatz dieser neuen Technologien und Aspekte ihrer aktuellen und möglichen zukünftigen Anwendung. Die Anzahl der zum Thema KI-basierte EKG-Analyse publizierten Studien steigt seit 2017 rasant an. Dies gilt vor allem für Untersuchungen, die Deep Learning (DL) mit künstlichen neuronalen Netzen (KNN) einsetzen. Inhaltlich geht es nicht nur darum, die Schwächen der klassischen EKG-Diagnostik mit Hilfe von KI zu überwinden und die diagnostische Güte des Verfahrens zu verbessern, sondern auch die Funktionalität des EKGs zu erweitern. Angestrebt wird die Erkennung spezieller kardiologischer und nichtkardiologischer Krankheitsbilder sowie die Vorhersage zukünftiger Krankheitszustände, z. B. die zukünftige Entwicklung einer linksventrikulären Dysfunktion oder das zukünftige Auftreten von Vorhofflimmern. Möglich wird dies, indem KI mittels DL in riesigen EKG-Datensätzen subklinische Muster findet und für die Algorithmen-Entwicklung nutzt. Die KI-unterstützte EKG-Analyse wird somit zu einem Screening-Instrument und geht weit darüber hinaus, nur besser als ein Kardiologe zu sein. Die erzielten Fortschritte sind bemerkenswert und sorgen in Fachwelt und Öffentlichkeit für Aufmerksamkeit und Euphorie. Bei den meisten Studien handelt es sich allerdings um Proof-of-Concept-Studien. Häufig werden private (institutionseigene) Daten verwendet, deren Qualität unklar ist. Bislang ist nur selten eine klinische Validierung der entwickelten Algorithmen in anderen Kollektiven und Szenarien erfolgt. Besonders problematisch ist, dass der Weg, wie KI eine Lösung findet, bislang meistens verborgen bleibt (Blackbox-Charakter). Damit steckt die KI-basierte Elektrokardiographie noch in den Kinderschuhen. Unbestritten ist aber schon absehbar, dass das EKG als einfach anzuwendendes und beliebig oft wiederholbares diagnostisches Verfahren auch in Zukunft nicht nur weiterhin unverzichtbar sein wird, sondern durch KI an klinischer Bedeutung gewinnen wird.
Aniridia-related keratopathy relevant cell signaling pathways in human fetal corneas
Authors: Vicente André , Sloniecka Marta , Liu Jing-Xia , Byström Berit , Pedrosa Domellöf Fátima
Published: May 2022

We aimed to study aniridia-related keratopathy (ARK) relevant cell signaling pathways [Notch1, Wnt/β-catenin, Sonic hedgehog (SHH) and mTOR] in normal human fetal corneas compared with normal human adult corneas and ARK corneas. We found that fetal corneas at 20 weeks of gestation (wg) and normal adult corneas showed similar staining patterns for Notch1; however 10–11 wg fetal corneas showed increased presence of Notch1. Numb and Dlk1 had an enhanced presence in the fetal corneas compared with the adult corneas. Fetal corneas showed stronger immunolabeling with antibodies against β-catenin, Wnt5a, Wnt7a, Gli1, Hes1, p-rpS6, and mTOR when compared with the adult corneas. Gene expression of Notch1, Wnt5A, Wnt7A, β-catenin, Hes1, mTOR, and rps6 was higher in the 9–12 wg fetal corneas compared with adult corneas. The cell signaling pathway differences found between human fetal and adult corneas were similar to those previously found in ARK corneas with the exception of Notch1. Analogous profiles of cell signaling pathway activation between human fetal corneas and ARK corneas suggests that there is a less differentiated host milieu in ARK.
Evidence of cell cycle re-entry in post-mitotic, terminally differentiated feline neurons
Authors: Wisnet Karolina , Payer Christoph H. F. , Bauder Barbara , Url Angelika
Published: May 2022

Parvovirus infections in dogs and cats are restricted to highly mitotically active tissues, predominantly to the epithelium of the gastrointestinal tract and, in cases of prenatal infections in cats, also to Purkinje cell neuroblasts. The evidence of parvovirus-infected mature feline neurons gave rise to reconsider the dogma of post-mitotically fixed and terminally differentiated neurons in the adult central nervous system. To elucidate the postulated capability of certain terminally differentiated feline neurons to re-enter the cell cycle, immunohistochemical double labeling using the transcription factor Sox2 and the tumor suppressor and cell cycle regulator retinoblastoma protein in its phosphorylated state (pRb) was performed. Formalin-fixed and paraffin-embedded brain tissue negative for parvovirus-antigen from 14 cats was compared to brain tissue from 13 cats with immunohistochemically confirmed cerebral parvovirus infection; the 27 cats were aged between 50 days of gestation (E50) and 5 years. Both groups revealed nuclear Sox2 and pRb immunosignals in numerous neurons, suggesting a more active state than mature neurons should have. Accordingly, parvovirus is not exclusively involved in the reactivation of the cell cycle machinery in those post-mitotic, terminally differentiated feline neurons.
Sexual differences in phenotypical predictors of floating status: body condition influences male but not female reproductive status in a wild passerine
Authors: Redondo Iraida , Pérez-Rodríguez Lorenzo , Monclús Raquel , Muriel Jaime , Gil Diego
Published: May 2022

Floaters constitute the sexually mature but non-breeding part of populations. Despite being ubiquitous in most species, knowledge about floaters is scarce. Ignoring this significant number of individuals may strongly bias our understanding of population dynamics and sexual selection processes. We used the spotless starling (Sturnus unicolor) to examine whether phenotypical and non-phenotypical variables from early and adult life predict reproductive status, focusing on the earliest age at which most individuals start to breed, when the percentage of floaters is the highest. We compiled data from a long-term study involving eight female and seven male cohorts of individuals PIT-tagged at birth. We compared a suite of nestling (condition, hatching date and brood size) and adult variables (condition, size and ornamentation) between floaters and breeders. We found that adult and nestling body condition strongly and positively influenced the likelihood of breeding in males. Path analysis revealed that male reproductive status could only be predicted by considering nestling body condition—the influence of this variable superseded adult body condition. Female reproductive status was only negatively associated with hatching date. Ornamentation was not associated with reproductive status in any of the sexes, although path analyses revealed that body condition was positively associated with throat feather length. We conclude that predictors of reproductive status are sex-specific in the spotless starling, suggesting an important role of body condition in access to breeding resources in males. Our results also highlight the long-term influence of early life on life trajectories and their potential implications on floating status.
Grazing by wild red deer can mitigate nutrient enrichment in protected semi-natural open habitats
Authors: Riesch Friederike , Wichelhaus Anya , Tonn Bettina , Meißner Marcus , Rosenthal Gert , Isselstein Johannes
Published: May 2022

Eutrophication through atmospheric nutrient deposition is threatening the biodiversity of semi-natural habitats characterized by low nutrient availability. Accordingly, local management measures aiming at open habitat conservation need to maintain habitat-specific nutrient conditions despite atmospheric inputs. Grazing by wild herbivores, such as red deer (Cervus elaphus), has been proposed as an alternative to mechanical or livestock-based measures for preserving open habitats. The role of red deer for nutrient dynamics in protected open habitat types, however, is yet unclear. Therefore, we collected data on vegetation productivity, forage removal, quantity of red deer dung and nutrient concentrations in vegetation and dung from permanent plots in heathlands and grasslands (eight plots à 225 m2 per habitat type) on a military training area inhabited by a large population of free-ranging red deer over one year. The annual nutrient export of nitrogen (N) and phosphorus (P) by red deer grazing was higher than the nutrient import through red deer excreta, resulting in an average net nutrient removal of 14 and 30 kg N ha−1 a−1 and 1.1 and 3.3 kg P ha−1 a−1 in heathlands and grasslands, respectively. Even when considering approximate local atmospheric deposition values, net nutrient depletion due to red deer grazing seemed very likely, notably in grasslands. Demonstrating that grazing by wild red deer can mitigate the effects of atmospheric nutrient deposition in semi-natural open habitats similarly to extensive livestock grazing, our results support the idea that red deer are suitable grazing animals for open habitat conservation.
Hierarchical goals contextualize local reward decomposition explanations
Authors: Rietz Finn , Magg Sven , Heintz Fredrik , Stoyanov Todor , Wermter Stefan , Stork Johannes A.
Published: May 2022

One-step reinforcement learning explanation methods account for individual actions but fail to consider the agent’s future behavior, which can make their interpretation ambiguous. We propose to address this limitation by providing hierarchical goals as context for one-step explanations. By considering the current hierarchical goal as a context, one-step explanations can be interpreted with higher certainty, as the agent’s future behavior is more predictable. We combine reward decomposition with hierarchical reinforcement learning into a novel explainable reinforcement learning framework, which yields more interpretable, goal-contextualized one-step explanations. With a qualitative analysis of one-step reward decomposition explanations, we first show that their interpretability is indeed limited in scenarios with multiple, different optimal policies—a characteristic shared by other one-step explanation methods. Then, we show that our framework retains high interpretability in such cases, as the hierarchical goal can be considered as context for the explanation. To the best of our knowledge, our work is the first to investigate hierarchical goals not as an explanation directly but as additional context for one-step reinforcement learning explanations.
Rock Properties and Modelled Stress State Uncertainties: A Study of Variability and Dependence
Authors: Ziegler Moritz O.
Published: May 2022

The safety and sustainability of subsurface applications requires a profound knowledge of the local stress state which is frequently assessed using 3D geomechanical-numerical models. Various factors lead to generally large uncertainties in these models. The variabilities in the rock properties as one of the sources of uncertainties and their influence on the modelled stress state is addressed herein. A generic 3D geomechanical-numerical model is used to investigate the influence of different distributions of variability and their effect on different stress states. The variability in rock properties clearly affects the uncertainties in the stress state in a positive correlation with differences that depend on the affected component of the stress tensor. The basic observation is that largest uncertainties are observed in the normal components of the stress tensor where the variabilities apparently are most effective. The same rock property variabilities affect the shear components uncertainties to a significantly lesser extent. Variabilities in the Young’s modulus and the Poisson’s ratio chiefly affect the uncertainties in $$\sigma _{xx}$$

σ

xx

and $$\sigma _{yy}$$

σ

yy

. The density variability, however, leads to highest uncertainties in $$\sigma _{zz}$$

σ

zz

. In general, variabilities in the Young’s modulus are most effective, followed by the Density and then the Poisson’s ratio. Furthermore, an influence of the tectonic stress regime on how the variability in the rock properties affects the stress state is observed. At the same time only a small effect is observed for different stress magnitudes. The eventual uncertainties in a modelled stress state depend not only on the uncertainties in the rock properties but also whether the uncertainties are found mainly in the Young’s modulus, the Poisson’s ratio or the Density. These findings indicate the importance to regard variabilities in rock properties as a source for significant uncertainties in geomechanical-numerical models. It is proposed to use the derived relations for an inexpensive quantification of uncertainties by means of a post-computation assignment of uncertainties to a stress model.
Ebenen therapeutischer Verantwortung – multiple Perspektiven in einer komplexen Welt
Authors: Schigl Brigitte , Klar Sabine , Kobbé Ulrich , Macke Karin , Tenschert Ekkehard
Published: May 2022

Der Text thematisiert Dimensionen des Handelns von Psychotherapeut_innen entlang einer Fallvignette, in der ein in den Praxisräumen ausgehängter Aufruf zur Covid-Impfung einen Abbruch der Psychotherapie durch die Patient_in auslöste. Dabei werden verschiedene Ebenen der Verantwortung von Psychotherapeut_innen aufgezeigt: Handeln auf individueller Ebene im Kontakt mit den Patient_innen, Handeln auf gesellschaftlicher Ebene – bzw. deren Einbezug in therapeutische Überlegungen. Schließlich auch daraus erwachsende Aspekte für die Ausbildung von Psychotherapeut_innen. Im Aufzeigen dieser unterschiedlichen Perspektiven sollen die Komplexität und Pluralität psychotherapeutischer Handlungsfelder und Ansätze sichtbar gemacht werden.
Monetary policy in an oil-dependent economy in the presence of multiple shocks
Authors: Drygalla Andrej
Published: May 2022

Russian monetary policy has been challenged by large and continuous private capital outflows and a sharp drop in oil prices during 2014. Both contributed to significant depreciation pressures on the ruble and led the central bank to give up its exchange rate management strategy. Against this background, this work estimates a small open economy model for Russia, featuring an oil price sector and extended by a specification of the foreign exchange market to correctly account for systematic central bank interventions. We find that shocks to the oil price and private capital flows substantially affect domestic variables such as inflation and output. Simulations for the estimated actual strategy and alternative regimes suggest that the vulnerability of the Russian economy to external shocks can substantially be lowered by adopting some form of inflation targeting. Strategies to target the nominal exchange rate or the ruble price of oil prove to be inferior.
High-intensity focused ultrasound therapy for pancreatic cancer
Authors: Sofuni Atsushi , Asai Yasutsugu , Mukai Shuntaro , Yamamoto Kenjiro , Itoi Takao
Published: May 2022

Pancreatic cancer (PC) has one of the poorest prognoses among solid cancers, and its incidence has increased recently. Satisfactory outcomes are not achieved with current therapies; thus, novel treatments are urgently needed. High-intensity focused ultrasound (HIFU) is a novel therapy for ablating tissue from the outside of the body by focusing ultrasonic waves from multiple sources on the tumor. In this therapy, only the focal area is heated to 80–100 ºC, which causes coagulative necrosis of the tissue, with hardly any impact on the tissue outside the focal area. Although HIFU is a minimally invasive treatment and is expected to be useful, it is not yet generally known. Here, we discuss the usefulness of HIFU treatment for un-resectable advanced PC using the results of previous research, meta-analyses, and systematic reviews on its efficacy and safety. HIFU therapy for un-resectable PC is useful for its anti-tumor effect and pain relief, and is expected to prolong survival time and improve quality of life. Although HIFU for PC has several limitations and further study is needed, this technique can be safely performed on un-resectable advanced PC. In future, HIFU could be utilized as a minimally invasive treatment strategy for PC patients with a poor prognosis.
The semantics of diversity in higher education: differences between the Global North and Global South
Authors: Pineda Pedro , Mishra Shweta
Published: May 2022

Inspired by neo-institutional theory, we explore whether the semantics of diversity appears to be global and universal through computer-assisted content analysis of 2378 publications. Diversity discourses are dominant, but only in the USA and Canada, UK and Ireland and Europe, not being present in Asia, Africa, the Middle East and Latin America. Diversity is interpreted differently across regions influenced by the local socio-political settings. Academic literature on diversity first appeared in the USA and Canada in the mid-1970s in relation to race and gender. In other English-speaking countries, diversity gained momentum only in the mid-2000s, with inclusion, gender, ethnicity and cultural diversity being the dominant terminologies. Later in that decade, diversity appeared in the academic literature in Europe, often framed as inclusion and gender. We did not find any evidence that the semantics of diversity has become global or universal and, therefore, question the cultural globalisation and the worldwide standardisation of academic knowledge around the valorisation of individual and collective differences.
Combination of Uniform Interpolants via Beth Definability
Authors: Calvanese Diego , Ghilardi Silvio , Gianola Alessandro , Montali Marco , Rivkin Andrey
Published: May 2022

Uniform interpolants were largely studied in non-classical propositional logics since the nineties, and their connection to model completeness was pointed out in the literature. A successive parallel research line inside the automated reasoning community investigated uniform quantifier-free interpolants (sometimes referred to as “covers”) in first-order theories. In this paper, we investigate cover transfer to theory combinations in the disjoint signatures case. We prove that, for convex theories, cover algorithms can be transferred to theory combinations under the same hypothesis needed to transfer quantifier-free interpolation (i.e., the equality interpolating property, aka strong amalgamation property). The key feature of our algorithm relies on the extensive usage of the Beth definability property for primitive fragments to convert implicitly defined variables into their explicitly defining terms. In the non-convex case, we show by a counterexample that covers may not exist in the combined theories, even in case combined quantifier-free interpolants do exist. However, we exhibit a cover transfer algorithm operating also in the non-convex case for special kinds of theory combinations; these combinations (called ‘tame combinations’) concern multi-sorted theories arising in many model-checking applications (in particular, the ones oriented to verification of data-aware processes).
Putative involvement of sirtuin modulators in LPS-induced sickness behaviour in mice
Authors: Kinra Manas , Ranadive Niraja , Mudgal Jayesh , Zhang Yuqing , Govindula Anusha , Anoopkumar-Dukie Shailendra , Davey Andrew K. , Grant Gary D. , Nampoothiri Madhavan , Arora Devinder
Published: May 2022

NAD+—dependent histone deacetylases (sirtuins 1–7) have been shown to be involved in various pathophysiological conditions including their involvement in cardiovascular, cancerous, neurodegenerative, immune dysregulation and inflammatory conditions. This study investigates the inflammomodulatory potential of resveratrol (RES), a sirtuin activator and sirtinol (SIR), a sirtuin inhibitor in lipopolysaccharide (LPS)-induced model of sickness behaviour in mice. Male Swiss albino mice were divided into five groups (n = 6) consisting of saline (SAL), LPS, RES, SIR, and fluoxetine (FLU) respectively, each group except LPS was prepared by intraperitoneally (i.p.) administration of SAL (10 mL/kg), RES (50 mg/kg), SIR (2 mg/kg) and FLU (10 mg/kg). Thirty minutes after the treatments, all the groups, except SAL were administered LPS (2 mg/kg, i.p.). The behavioural assays including, open field test, forced swim test, and tail suspension tests were conducted 1 h after LPS challenge. LPS administration significantly reduced the locomotor activity along with inducing a state of high immobility and that was prevented by pretreatment with RES and SIR. Further, various proinflammatory cytokines (TNF-α, IL-6, and IL-1β), and oxidative stress markers (MDA and GSH) were found to be significantly elevated in the brain homogenates after LPS treatment. SIR pretreatment abrogated the LPS-induced neuroinflammatory and oxidative stress changes, whereas RES was only effective in reducing the oxidative stress and TNF-α levels. The results of this study speculate that the role of SIRT modulators in neuroinflammatory conditions could vary with their dose, regimen and chemical properties. Further studies with detailed molecular and pharmacokinetic profiling will be needed to explore their therapeutic potentials.
SOLar-STellar Irradiance Comparison Experiment II (SOLSTICE II): End-of-Mission Validation of the SOLSTICE Technique
Authors: Snow Martin , McClintock William E. , Woods Thomas N. , Elliott Joshua P.
Published: May 2022

The SOLar-STellar Irradiance Comparison Experiment (SOLSTICE: McClintock, Rottman, and Woods, Solar Phys.230, 225, 2005) onboard the SOlar Radiation and Climate Experiment (SORCE: Rottman, Solar Phys.230, 7, 2005) observed ultraviolet solar spectral irradiance (SSI) from 2003 – 2020. This article gives an overview of the end-of-mission algorithms and calibration of SOLSTICE. Many of the algorithms were updated after the early mission, either due to an improved understanding of the instrument and the space environment, or due to operational constraints as the spacecraft systems aged. We validate the final official data version (V18) with comparisons to other observations and models. The SOLSTICE observations of the solar-cycle variability in the ultraviolet are compared to model estimates.
Measuring and modeling context-dependent preferences for hearing aid settings
Authors: Pasta Alessandro , Petersen Michael Kai , Jensen Kasper Juul , Pontoppidan Niels Henrik , Larsen Jakob Eg , Christensen Jeppe Høy
Published: May 2022

Despite having individual perceptual preferences toward sounds, hearing aid users often end up with default hearing aid settings that have no contextual awareness. However, the introduction of smartphone-connected hearing aids has enabled a rethinking of hearing aids as user-adaptive systems considering both individual and contextual differences. In this study, we aimed to investigate the feasibility of such context-aware system for providing hearing aid users with a number of relevant hearing aid settings to choose from. During normal real-world hearing aid usage, we applied a smartphone-based method for capturing participants’ listening experience and audiological preference for different intervention levels of three audiological parameters (Noise Reduction, Brightness, Soft Gain). Concurrently, we collected contextual data as both self-reports (listening environment and listening intention) and continuous data logging of the acoustic environment (sound pressure level, signal-to-noise ratio). First, we found that having access to different intervention levels of the Brightness and Soft Gain parameters affected listening satisfaction. Second, for all three audiological parameters, the perceived usefulness of having access to different intervention levels was significantly modulated by context. Third, contextual data improved the prediction of both explicit and implicit intervention level preferences. Our findings highlight that context has a significant impact on hearing aid preferences across participants and that contextual data logging can help reduce the space of potential interventions in a user-adaptive system so that the most useful and preferred settings can be offered. Moreover, the proposed mixed-effects model is suitable for capturing predictions on an individual level and could also be expanded to predictions on a group level by including relevant user features.
Novel organic draw solution in forward osmosis process for fertigation: performance evaluation and flux prediction
Authors: Al Bazedi Ghada , Soliman Noha , Sewilam Hani
Published: May 2022

Fertilizer-drawn forward osmosis (FDFO) has received a lot of attention for its potential for producing fertigated water for agriculture purposes. To minimize the use of chemical-based fertilizers and support sustainable organic agriculture, this work investigated the separation performance of FO membrane for different feed concentrations (FS) of brackish water using microalgae Spirulina platensis as an organic fertilizer draw solution (DS). Different feed solution concentrations were investigated ranging 3–20 g/L NaCl, with various draw solutions of spirulina ranging 280–440 g/L. The performance was measured by water flux and recovery. The results showed that using spirulina as a draw solution is a promising solution for fertigation purposes. The results showed that Na+ in feed solution is concentrated by 41%, Cl- by 36%, and spirulina is diluted by 20% for feed salinity 5000 mg/L. The highest flux obtained with different feed solution 3000/5000/10,000/20,000 mg/L were 9/6/4.5/7 for draw solution concentration of 360/360/400/420 g/L. The calculated specific reverse solute flux (SRSF) JS/JW varies from 0.1 and 0.8 for different explored FS/DS concentrations. Flux decline and the down-time was investigated for the highest flux observed, showing 290 min of operation before cleaning action is required.