bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pan‐HSP90 ligand binding reveals isoform‐specific differences in plasticity and water networks
Authors: Stachowski Timothy R. , Nithianantham Stanley , Vanarotti Murugendra , Lopez Karlo , Fischer Marcus 
Published: March 2023

AbstractIsoforms of heat shock protein 90 (HSP90) fold oncoproteins that facilitate all 10 hallmarks of cancer. However, its promise as a therapeutic target remains unfulfilled as there is still no FDA‐approved drug targeting HSP90 in disease. Among the reasons hindering progress are side effects caused by pan‐HSP90 inhibition. Selective targeting of the four isoforms is challenging due to high sequence and structural similarity. Surprisingly, while decades of drug discovery efforts have produced almost 400 human HSP90 structures, no single ligand has been structurally characterized across all four human isoforms to date, which could reveal structural differences to achieve selectivity. To better understand the HSP90 landscape relevant for ligand binding and design we take a three‐pronged approach. First, we solved the first complete set of structures of a single ligand bound to all four human isoforms. This enabled a systematic comparison of how side‐chains and water networks respond to ligand binding across isoforms. Second, we expanded our analysis to publicly available, incomplete isoform‐ligand series with distinct ligand chemistry. This highlighted general trends of protein and water mobility that differ among isoforms and impact ligand binding. Third, we further probed the Hsp90α conformational landscape for accommodating a congeneric series containing the purine scaffold common to HSP90 inhibitors. This revealed how minor ligand modifications flip ligand poses and perturb water and protein conformations. Taken together, this work illustrates how a systematic approach can shed new light on an “old” target and reveal hidden isoform‐specific accommodations of congeneric ligands that may be exploited in ligand discovery and design.
A pharmacokinetic drug–drug interaction study between rosuvastatin and emvododstat, a potent anti‐SARS‐CoV‐2 (COVID‐19) DHODH (dihydroorotate dehydrogenase) inhibitor
Authors: Morton Terri L. , Laskin Oscar L. , Kaushik Diksha , Lee Lucy , Ma Jiyuan , Kristensen Allan , O'Keefe Kylie , Golden Lee , Klein Matthew , Kong Ronald 
Published: March 2023

AbstractA therapeutic agent that targets both viral replication and the hyper‐reactive immune response would offer a highly desirable treatment for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2; COVID‐19) management. Emvododstat (PTC299) was found to be a potent inhibitor of immunomodulatory and inflammation‐related processes by the inhibition of dihydroorotate dehydrogenase (DHODH) to reduce SARS‐CoV‐2 replication. DHODH is the rate‐limiting enzyme of the de novo pyrimidine nucleotide biosynthesis pathway. This drug interaction study was performed to determine whether emvododstat was an inhibitor of breast cancer resistance protein (BCRP) transporters in humans. Potential drug–drug interactions (DDIs) between emvododstat and a BCRP transporter substrate (rosuvastatin) were investigated by measuring plasma rosuvastatin concentrations before and after emvododstat administration. There was no apparent difference in rosuvastatin plasma exposure. The geometric means of maximum plasma rosuvastatin concentrations (Cmax) were 4369 (rosuvastatin) and 5141 pg/mL (rosuvastatin + emvododstat) at 4 h postdose. Geometric mean rosuvastatin area under the concentration–time curve (AUC) from time 0 to the last measurable plasma concentration was 45 616 and 48 975 h·pg/mL when administered alone and after 7 days of b.i.d. emvododstat dosing, respectively. Geometric least squares mean ratios for Cmax and AUC were approximately equal to 1. Overall, administration of multiple doses of 100 mg emvododstat b.i.d. for 7 days in combination with a single dose of rosuvastatin was safe and well tolerated. Emvododstat can be safely administered with other BCRP substrate drugs. Hence, pharmacokinetic DDI mediated via BCRP inhibition is not expected when emvododstat and BCRP substrates are coadministered.
Sirolimus‐ and cyclosporine‐loaded nanostructured lipid carriers: Development, characterization, and in vitro evaluation in T‐cell profiles of patients with a history of recurrent pregnancy loss
Authors: Parhizkar Forough , Yousefi Mehdi , Soltani‐Zangbar Mohammad Sadegh , Parhizkar Zahra , Aghebati‐Maleki Leili , Abbaspour‐Ravasjani Soheil , Motavalli Roza , Alizadegan Amin , Mojahedi Maryam , Baharaghdam Sina , Kamrani Amin , Danaii Shahla , Talebi Mehdi , Jadidi‐Niaragh Farhad , Hamishehkar Hamed , Kafil Hossein Samadi , Mahmoodpoor Ata , Heris Javad Ahmadian 
Published: March 2023

AbstractPurposeThe authors developed nanostructured lipid carriers (NLCs) loaded with sirolimus (SRL) and cyclosporine (CsA) to improve their therapeutic efficacy in recurrent pregnancy loss (RPL) patients.MethodsMono‐delivery and co‐delivery of SRL and CsA by NLCs (S‐NLCs, C‐NLCs, and S‐C‐NLCs) were developed. The MTT assay was used to study the optimum dose of formulations. PCR, Western blotting, and ELISA were also conducted.ResultsWell‐designed nanodrugs with a suitable size, zeta potential, desirable encapsulation efficiency drug loading, and cellular uptake confirmed optimum formulations. Based on cell viability, the amounts of SRL and CsA could be reduced greatly due to the co‐delivery by NLCs. Following S‐NLCs and C‐NLCs interventions in T cells of patients with RPL and immune abnormality, a significant difference was observed in transcription factors and cytokine levels of Th1, Th17, and Tregs compared with healthy samples. Thus, a higher level of pro‐inflammatory cytokines (IFN‐γ, TNF‐α, IL‐17, and IL‐21) and their regulators (T‐bet and RORγt), as well as a lower level of an anti‐inflammatory cytokine (IL‐10) and its regulatory (Foxp3), were observed. However, no significant difference was found following the S‐C‐NLCs intervention.ConclusionsS‐C‐NLCs effectively balance the immune responses in peripheral T cells in RPL patients to induce maternal immune tolerance.
An integrated design method for active fault diagnosis and control
Authors: Wang Jing , Lv Xueyan , Meng Zhou , Puig Vicenç 
Published: March 2023

SummaryThe injection of an auxiliary input signal for active fault diagnosis may cause the change of system control performance in closed‐loop operation. This paper presents a novel integrated design method for active fault diagnosis and tracking control in order to facilitate the detection of incipient faults, meanwhile ensuring the normal operation of the closed‐loop system. First, a zonotopic filter is generated based on radius minimization method to estimate the uncertain bound set of systems states. Then, an auxiliary input signal is designed to separate the reachable sets of the system in healthy and faulty operation situations. Generally, the auxiliary input signal is required to be designed minimizing the system closed‐loop performance degradation. In this paper, a tracking controller is designed altogether with the auxiliary input signal to make the system output track a given reference. An optimal index is proposed to minimize simultaneously the energy of the auxiliary input signal and the output tracking error. Next, a fault detection logic is provided based on checking whether the closed‐loop system state belongs to healthy zonotope. Finally, the feasibility and advantages of this work are verified by means of a numerical example.
A comparison of two approaches to dynamic prediction: Joint modeling and landmark modeling
Authors: Li Wenhao , Li Liang , Astor Brad C. 
Published: March 2023

SummaryJoint modeling and landmark modeling are two mainstream approaches to dynamic prediction in longitudinal studies, that is, the prediction of a clinical event using longitudinally measured predictor variables available up to the time of prediction. It is an important research question to the methodological research field and also to practical users to understand which approach can produce more accurate prediction. There were few previous studies on this topic, and the majority of results seemed to favor joint modeling. However, these studies were conducted in scenarios where the data were simulated from the joint models, partly due to the widely recognized methodological difficulty on whether there exists a general joint distribution of longitudinal and survival data so that the landmark models, which consists of infinitely many working regression models for survival, hold simultaneously. As a result, the landmark models always worked under misspecification, which caused difficulty in interpreting the comparison. In this paper, we solve this problem by using a novel algorithm to generate longitudinal and survival data that satisfies the working assumptions of the landmark models. This innovation makes it possible for a “fair” comparison of joint modeling and landmark modeling in terms of model specification. Our simulation results demonstrate that the relative performance of these two modeling approaches depends on the data settings and one does not always dominate the other in terms of prediction accuracy. These findings stress the importance of methodological development for both approaches. The related methodology is illustrated with a kidney transplantation dataset.
Synergistically Achieving Superior Sodium Storage of Metal Selenides by Constructing N‐Doped Carbon Foams and Utilizing Cu‐Driven Replacement Reaction
Authors: Zhu Chao , Long Tao , Feng Bin , Wu Chunyang , Yu Qinqin , Ding Yuan‐Li 
Published: March 2023

AbstractMetal selenides are considered as one of the most promising anode materials for Na‐ion batteries owing to high specific capacity and relatively higher electronic conductivity compared with metal sulfides or oxides. However, such anodes still suffer from huge volume change upon repeated Na+ insertion/extraction processes and simultaneously undergo severe shuttle effect of polyselenides, thus leading to poor electrochemical performance. Herein, a facile chemical‐blowing and selenization strategy to fabricate 3D interconnected hybrids built from metal selenides (MSe, M = Mn, Co, Cr, Fe, In, Ni, Zn) nanoparticles encapsulated in in situ formed N‐doped carbon foams (NCFs) is reported. Such hybrids not only provide ultrasmall active nanobuilding blocks (≈15 nm), but also efficiently anchor them inside the conductive NCFs, thus enabling both high‐efficiency utilization of active components and high structural stability. On the other hand, Cu‐driven replacement reaction is utilized for efficiently inhibiting the shuttle effect of polyselenides in ether‐based electrolyte. Benefiting from the combined merits of the unique MSe@NCFs and the utilization of the conversion of metal selenides to copper selenides, the as‐obtained hybrids (MnSe as an example) exhibit superior rate capability (386.6 mAh g−1 up to 8 A g−1) and excellent cycling stability (347.7 mAh g−1 at 4.0 A g−1 after 1200 cycles).
Electrolyte Engineering on Performance Enhancement of NiCo2S4 Anode for Sodium Storage
Authors: Fan Shanshan , Liu Haiping , Xie Ying , Bi Sifu , Meng Xiaohuan , Zhang Kaiqi , Sun Liang , Zhang Shilin , Guo Zaiping 
Published: March 2023

AbstractNiCo2S4 is an attractive anode for sodium‐ion batteries (SIBs) due to its high capacity and excellent redox reversibility. Practical deployment of NiCo2S4 electrode in SIBs, however, is still hindered by the inferior capacity and unsatisfactory cycling performance, which result from the mismatch between the electrolyte chemistry and electrode. Herein, a functional electrolyte containing 1.0 m NaCF3SO3 in diethylene glycol dimethyl ether (DEGDME) (1.0 m NaCF3SO3‐DEGDME) is developed, which can be readily used for NiCo2S4 anode with high initial coulomb efficiency (96.2%), enhanced cycling performance, and boosted capacities (341.7 mA h g−1 after 250 continuous cycles at the current density of 200 mA g−1). The electrochemical tests and related phase characterization combined with density functional theory (DFT) calculation indicate the ether‐based electrolyte is more suitable for the NiCo2S4 anode in SIBs due to the formation of a stable electrode–electrolyte interface. Additionally, the importance of the voltage window is also demonstrated to further optimize the electrochemical performance of the NiCo2S4 electrode. The formation of sulfide intermediates during charging and discharging is predicted by combining DFT and verified by in situ XRD and HRTEM. The findings indicate that electrolyte engineering would be an effective way of performance enhancement for sulfides in practical SIBs.
Manipulation of the through‐space interactions in diphenylmethane
Authors: Tu Weihao , Xiong Zuping , Zhang Ziteng , Zhang Jianyu , Wang Lei , Xie Yuan , Wang Yipu , Zhang Haoke , Sun Jing Zhi , Tang Ben Zhong 
Published: March 2023

AbstractThrough‐space interaction (TSI) has been proven to play an important role in the newly emerging clusteroluminescence (CL) phenomenon. However, it is still a big challenge to manipulate the TSI at the molecular level due to the unclear relationship between the non‐conjugated structure and TSI properties. Herein, the TSI in diphenylmethane is manipulated by breaking its symmetric structures and changing the isolated subunits. Finally, the CL wavelength and efficiency of diphenylmethane are successfully regulated at the aggregate state.
Effective Teachers of Multilingual Learners: A Mixed‐Method Study ofUKandUSCritical Sociocultural Teaching Practices
Authors: Flynn Naomi , Teemant Annela , Viesca Kara Mitchell , Perumal Ratha 
Published: March 2023

AbstractThis convergent parallel mixed‐method study (quan + QUAL) relies on systematic classroom observations of mainstream teachers considered highly effective with multilingual learners in the United Kingdom and the United States (N = 9). Using a critical sociocultural theoretical lens, we use an established quantitative observation rubric and lesson field notes to capture real‐world teaching practices. Using deductive reasoning to merge closed‐ and open‐ended observation data, we illuminate the features of highly effective teaching for multilingual students. Evidence demonstrates that elements of challenge in activity design and teacher presentation, prioritizing language and literacy development, and modeling, were practices with the highest consistency across countries. At the same time, other features leave room for future growth. Lesson analysis unpacked various ways teachers enact effective teaching based on country context. Despite educational policies that may conflict with strong teaching for multilingual students, linguistically responsive teachers in both countries transcend curricular and testing constraints by intentionally enacting lessons that richly scaffold learning.
Disciplinary Reading, Action, and Social Change
Authors: Cervetti Gina N. , Pearson P. David 
Published: March 2023

AbstractIn their Four Resources Model, Freebody and Luke (1990) described four roles that readers take as they engage with texts: the code breaker, meaning maker, text user/analyst, and text critic. In this article, we propose the addition of a fifth role, the text actor. In this role, readers engage with texts that can incite, inform, and inspire them to take action to produce change within the many communities in which they reside, including the classroom, local community, and national community. Creating opportunities to assume this role is a potentially important part of preparing students for active social and civic participation, and it is especially important in this historical moment, when we are confronted with significant challenges that require global problem solving and participation. We describe the text actor role and share examples of how students can take on this role in disciplinary learning.
French Influence on Guarino Guarini’s Theory of Stereotomy
Authors: Taraldsen Simen Dalen 
Published: March 2023

AbstractThis research concerns stereotomy in Baroque architectural theory. Specifically, it explores French influence on Guarino Guarini’s theory of stereotomy. The research argues that the French influence on Guarini’s theory of stereotomy was limited. The argument is sustained by the scarcity of references to French sources in Guarini’s theory of stereotomy.
Häusliche Pflegearrangements: Untersuchung der Inanspruchnahme von Unterstützungsleistungen im Zusammenhang mit dem sozioökonomischen Status
Authors: Englert Nathalie , Peters Lara , Przysucha Mareike , Noelle Marco , Hülsken-Giesler Manfred , Büscher Andreas 
Published: March 2023

ZusammenfassungHintergrundNationale und internationale Befunde weisen auf den Einfluss sozioökonomischer Faktoren auf häusliche Pflegearrangements hin. Demografische und soziale Entwicklungen begründen die Annahme einer steigenden Zahl pflegebedürftiger Menschen aus ressourcenschwachen Gruppen und damit die zunehmende Bedeutung der Langzeitversorgung im häuslichen Umfeld.Ziel der ArbeitEs wird untersucht, ob Einkommen und Bildung der pflegebedürftigen Menschen und ihrer Pflegepersonen mit der Inanspruchnahme von Unterstützungsleistungen bei der Gestaltung häuslicher Pflegearrangements in Zusammenhang stehen.Material und MethodenQuantitative Sekundärdatenanalyse einer Befragung von Mitgliedern des Sozialverbands VdK. Die statistische Auswertung umfasst deskriptive Analysen sowie die Analyse von Zusammenhängen zwischen sozioökonomischen Merkmalen und Merkmalen des Pflegearrangements.ErgebnisseEin Zusammenhang von Einkommen und Versorgungsnutzung kann bei der Inanspruchnahme der sog. 24-Stunden-Pflege nachgewiesen werden, die häufiger bei hohem Einkommen zu finden ist. Weitere Einkommenseffekte zeigen sich beim Nutzungsumfang von Pflegediensten und Haushaltshilfen sowie bei wohnraumanpassenden Maßnahmen. Höhere Bildung geht mit einer gesteigerten Nutzung von Beratungsangeboten einher. Die Einschätzung der Pflegesituation fällt negativer aus, je niedriger das Einkommen ist.DiskussionDie Ergebnisse weisen darauf hin, dass Phänomene sozialer Ungleichheit in der Pflege existieren und die Möglichkeiten zur Gestaltung häuslicher Pflege durch sozioökonomische Faktoren beeinflusst werden. Zugleich zeigt die Studie Herausforderungen bei der Auseinandersetzung mit sozialer Ungleichheit auf und gibt Orientierung für weitere Forschung, die angesichts gesellschaftlicher Trends an Bedeutung gewinnt.
Therapie der chronischen Rhinosinusitis mit Polyposis nasi (CRScNP) mit monoklonalen Antikörpern (Biologika): S2k-Leitlinie der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie (DGHNO-KHC) und der Deutschen Gesellschaft für Allgemeinmedizin und Familienmedizin (DEGAM)
Authors: Pfaar Oliver , Beule Achim Georg , Laudien Martin , Stuck Boris A. ,   erweiterte Leitliniengruppe ‚Biologika bei CRScNP‘, Aletsee Christoph , Klimek Ludger , Milger-Kneidinger Katrin , Popert Uwe , Rose Markus , Wagenmann Martin 
Published: March 2023

ZusammenfassungMonoklonale Antikörper (sog. Biologika) können bei chronischer Rhinosinusitis mit Nasenpolypen (CRScNP, im englischen Sprachgebrauch CRSwNP) im Rahmen ihrer Zulassung verordnet werden. Allerdings ist die Verordnung auf die schwere CRScNP ohne Krankheitskontrolle begrenzt, wobei bestimmte Voraussetzungen zu beachten sind. Derzeit sind Dupilumab, Omalizumab und Mepolizumab zugelassen, in der Literatur gibt es entsprechende Evidenz für ihre Wirksamkeit und Sicherheit. Es ist davon auszugehen, dass zukünftig weitere Biologika in dieser Indikation zugelassen werden. Die Schwere der Erkrankung sollte vor Therapieeinleitung sowie die Wirksamkeit dieser Therapie nach einem angemessenen Zeitraum objektiv und subjektiv überprüft werden. Hierfür kann der in diesem aktualisierten Leitlinien-Kapitel vorgeschlagene Dokumentationsbogen verwendet werden. Bei Vorliegen von relativen Kontraindikationen sollte nur nach differenzierter Abwägung durch erfahrene Ärzt*innen und als Einzelfallentscheidung ein Therapieversuch mit Biologika erfolgen. Zusammenfassend hat das vorliegende Leitlinien-Kapitel zum Ziel, angesichts der zunehmenden Evidenz zur Therapie mit diesen Substanzen bzw. der zunehmenden Zahl an Zulassungen unterschiedlicher Biologika zu einer qualitativ hochwertigen Versorgung von erwachsenen Patient*innen mit dieser Therapieform beizutragen.
Tree languages and branched groups
Authors: Bartholdi Laurent , Noce Marialaura 
Published: March 2023

AbstractWe study the portraits of isometries of rooted trees—the labelling of the tree, at each vertex, by the permutation of its descendants—in terms of languages. We characterize regularly branched self-similar groups in terms of $$\omega $$
ω
-regular languages. We deduce the algorithmic decidability of some problems, such as the comparison of regularly branched contracting groups, and their orbit structure on the boundary of the rooted tree.
Effective Dynamics of Extended Fermi Gases in the High-Density Regime
Authors: Fresta Luca , Porta Marcello , Schlein Benjamin 
Published: March 2023

AbstractWe study the quantum evolution of many-body Fermi gases in three dimensions, in arbitrarily large domains. We consider both particles with non-relativistic and with relativistic dispersion. We focus on the high-density regime, in the semiclassical scaling, and we consider a class of initial data describing zero-temperature states. In the non-relativistic case we prove that, as the density goes to infinity, the many-body evolution of the reduced one-particle density matrix converges to the solution of the time-dependent Hartree equation, for short macroscopic times. In the case of relativistic dispersion, we show convergence of the many-body evolution to the relativistic Hartree equation for all macroscopic times. With respect to previous work, the rate of convergence does not depend on the total number of particles, but only on the density: in particular, our result allows us to study the quantum dynamics of extensive many-body Fermi gases.
Growth rate and projected age at sexual maturity for immature hawksbill turtles and green turtles foraging in the remote marine protected area of Aldabra Atoll, Seychelles
Authors: Sanchez Cheryl L. , Bunbury Nancy , Mortimer Jeanne A. , A’Bear Luke , Betts Michael , von Brandis Rainer , Burt April J. , Cooke Lorraine , van de Crommenacker Janske , Currie Jock C. , Doak Naomi , Fleischer-Dogley Frauke , Mederic Emma , Mels Bruno , Pistorius Pierre , Richards Heather , Casale Paolo 
Published: March 2023

AbstractChanges in marine ecosystems from human stressors, and concerns over how species will respond to these changes have emphasized the importance of understanding and monitoring crucial demographic parameters for population models. Long-lived, migratory, marine vertebrates such as sea turtles are particularly vulnerable to changes. Life-history parameters like growth-in-body size can be largely influenced by environmental processes which can impact population growth. We analyzed a 40-year (1981–2021) capture-mark-recapture dataset from the protected UNESCO World Heritage Site, Aldabra Atoll, Seychelles, to estimate key population parameters, including body growth, for immature green turtles (Chelonia mydas) and hawksbill turtles (Eretmochelys imbricata). Curved carapace length (CCL) range was 34.3–110.9 cm (mean ± SD: 51.0 ± 11.4 cm, n = 1191) for green turtles and 28.7–89.4 cm (47.7 ± 14.4 cm, n = 538) for hawksbill turtles. Recapture events, with an 11-month minimum period, revealed a mean annual growth rate of 3.2 ± 1.5 cm year−1 for green turtles (n = 75) and 2.8 ± 1.4 cm year−1 for hawksbill turtles (n = 110). Hawksbill turtles exhibited a non-monotonic growth rate while no significant growth-size relationship was detected for green turtles. Green turtle mean annual growth per 10-cm size class was highest in the larger size classes (50‒69.9 cm). Hawksbill turtle growth rate was highest in the larger size classes (50‒69.9 cm) then declined in the largest size class (70‒79.9 cm). Green turtles and hawksbill turtles may spend > 8 and 18 years, respectively, using Aldabra, Seychelles, as a foraging ground.