bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

AbstractEvolutionary 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

Abstract
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

AbstractHumans 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

AbstractAntarctic 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

AbstractThis 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

Abstract
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

ZusammenfassungAuch 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

ZusammenfassungWährend 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

AbstractWe 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

AbstractParvovirus 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

AbstractFloaters 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.