bluuebunny/crossref_metadata_2025_split huggingface dataset:
New tetracyclic systems integrated thienopyridine scaffold as an anti-dementia lead: in silico study and biological screening
Authors: Mahmoud Zeinab , Mohamed Lamia W. , Mohamed Khaled O. , Sayed Hadeer S. , Abd El Fattah May A. , El-Malah Afaf 
Published: February 2023

AbstractAlzheimer’s disease (AD) is a multifactorial incurable neurodegenerative disorder. To date, cholinesterase inhibitors (ChEI) are the mainstay line of treatment to ameliorate the symptoms of AD. Tacrine and donepezil are considered two important cornerstones of anti-dementia drugs. Accordingly, novel series of hexahydrobenzothienocyclopentapyridines, octahydrobenzo-thienoquinolines, hexahydrocyclopenta(thienoquinoline/thienodipyridine), and octahydropyrido-thienoquinolines were efficiently synthesized from readily available reagent, e.g. cyclohexanones, cyclopentanone, and 1-methyl-piperidin-4-one to afford 14 new compounds. All new compounds were screened against their acetylcholinesterase, butyrylcholinesterase, and β-amyloid protein inhibition. In AChE inhibition assay, compound 3,7-dimethyl-1,2,3,4,7,8,9,10-octahydrobenzo[4,5]thieno[2,3-b]quinolin-11-amine (2h) showed IC50 value 9.24 ± 0.01 μM × 10−2 excelling tacrine. Compound 1,7-dimethyl-1,2,3,4,7,8,9,10-octahydrobenzo[4,5]thieno[2,3-b]quinolin-11-amine (2e) possess excellent IC50 values 0.58 ± 0.02 μM × 10−2 and 0.51 ± 0.001 μM × 10−4 for both butyrylcholinesterase and β-amyloid protein inhibition assays, sequentially. In silico ADME studies were investigated for the promising members (octahydrobenzo-thienoquinolines 2c, 2d, 2e, 2h, 2i, and octahydropyrido-thienoquinolines 4e) and all the results were illustrated. A comparative docking study was conducted between the promising members and both tacrine and donepezil in both acetyl and butyryl choline active sites. The results revealed extra binding patterns and good agreement with the biological results.
Toll-like receptor-3 contributes to the development of aortic valve stenosis
Authors: Niepmann Sven Thomas , Willemsen Nicola , Boucher Ann Sophie , Stei Marta , Goody Philip , Zietzer Andreas , Bulic Marko , Billig Hannah , Odainic Alexandru , Weisheit Christina Katharina , Quast Christine , Adam Matti , Schmidt Susanne V. , Bakhtiary Farhad , Jansen Felix , Nickenig Georg , Latz Eike , Zimmer Sebastian 
Published: February 2023

AbstractAortic valve stenosis (AS) development is driven by distinct molecular and cellular mechanisms which include inflammatory pathways. Toll-like-receptor-3 (TLR3) is a lysosomal pattern-recognition receptor that binds double-stranded RNA and promotes pro-inflammatory cellular responses. In recent years, TLR3 has emerged as a major regulator of vascular inflammation. The exact role of TLR3 in the development of AS has not been investigated. Isolated human valvular interstitial cells (VICs) were stimulated with the TLR3-agonist polyIC and the resulting pro-inflammatory and pro-osteogenic response measured. Severe AS was induced in wildtype- and TLR3−/− mice via mechanical injury of the aortic valve with a coronary springwire. TLR3 activation was achieved by polyIC injection every 24 h after wire injury, while TLR3 inhibition was realized using Compound 4a (C4a) every 48 h after surgery. Endothelial mesenchymal transition (EndoMT) of human valvular endothelial cells (VECs) was assessed after polyIC stimulation. Stimulation of human VICs with polyIC promoted a strong inflammatory and pro-osteogenic reaction. Similarly, injection of polyIC marginally increased AS development in mice after wire injury. AS induction was significantly decreased in TLR3−/− mice, confirming the role of endogenous TLR3 ligands in AS pathology. Pharmacological inhibition of TLR3 with C4a not only prevented the upregulation of inflammatory cytokines and osteogenic markers in VICs, and EndoMT in VECs, but also significantly abolished the development of AS in vivo. Endogenous TLR3 activation significantly contributes to AS development in mice. Pharmacological inhibition of TLR3 with C4a prevented AS formation. Therefore, targeting TLR3 may be a viable treatment option.
Retrospective analysis of mortality and quality of life after hip disarticulation or hemipelvectomy: a report on 15 patients
Authors: Schindler Melanie , Baertl Susanne , Walter Nike , Lang Siegmund , Szymski Dominik , Alt Volker , Rupp Markus 
Published: February 2023

Abstract
Background
Hip disarticulation and hemipelvectomy are defined as major ablative amputations of the lower limb. Due to the small number of patients, little is known about the outcome and follow-up.

Aims
We aimed to assess (1) reasons for performed major ablative surgeries such as hip disarticulation and hemipelvectomy in a German center for trauma and orthopedic surgery. (2) In addition, mortality and quality of life after hip disarticulation and hemipelvectomy as well as (3) patient and treatment characteristics should be investigated.

Methods
During a period of twelve years, 15 patients underwent hip disarticulation or hemipelvectomy. Mortality, EQ-5D-3L quality of life by EQ-5D-3L and time-trade-off (TTO), VAS, cause of disarticulation, length of hospital stays, revisions, comorbidities, Charlson comorbidity index (CCI), and ASA score were evaluated retrospective for all patients.

Results
The overall mortality rates were 26.7% at 30 days, 60.0% after one year and 66.7% after three years. The five surviving patients reported about moderate problems in the EQ-5D-3L. The average VAS score reached 45 (range 15–65). The mean TTO was 9.8 (range 6–12). Indications for amputation were infection (n = 7), tumor (n = 6), trauma (n = 1) and ischemia (n = 1).

Conclusion
Hip disarticulation and hemipelvectomy are followed by a high postoperative mortality. Quality of life of the affected patients is impaired in long-term follow-up. Especially amputations performed due to infections show high mortality within one month after surgery despite average young age and low CCI. Surgeons should be aware of this devastating outcome and extraordinary vigilant for these vulnerable patient cohorts.
Inter-population differences in acetabular senescence: relevance in age-at-death estimation
Authors: San-Millán Marta , Rissech Carme 
Published: February 2023

AbstractSince investigation of the timing of the skeletal traits among the acetabula of different populations is lacking, this study aims to evaluate the relevance of geographical origin in the acetabulum aging process and in the usability of the SanMillán-Rissech aging method. The acetabula of 826 European North Americans derived from the Bass Collection (USA) have been analyzed and compared with 611 Portuguese acetabula from the Luis Lopes Collection (Portugal) applying the most updated acetabular age estimation technique (2017). After evaluating and comparing the acetabular aging rates between both populations by Mann–WhitneyUtests, the inaccuracy values (bias and absolute error) were analyzed and compared using population-specific reference samples and using references differing in geographical origin by Wilcoxon tests. In general terms, the North Americans age faster than the Portuguese, especially the females, reaching the consecutive acetabular stages at younger ages. Regarding the SanMillán-Rissech method accuracy, using population-specific reference samples produces, as a general rule, better outcomes. In addition, an exhaustive meta-analysis of inaccuracy values has demonstrated that this method provides better estimation values than pubic symphysis and auricular surfaces regardless of the geographic coherence of the reference sample. These inter-population skeletal differences are derived from different factors than age, highlighting the impact of both biological and social background on age estimation. A thorough analysis of the skeletal age-based timing becomes essential to understanding, deciphering and being able to minimize bias and potential inaccuracy or even counteract them when applying the age estimation methods to different populations.
A New Insight into the Stability of Precariously Balanced Rocks
Authors: Ludmány Balázs , Pérez-Rey Ignacio , Domokos Gábor , Muñiz-Menéndez Mauro , Alejano Leandro R. , Sipos András Á. 
Published: February 2023

AbstractLarge granitic boulders resting on steep slopes represent considerable safety hazards that largely depend on the location of the contact surface characterized by the impression d, denoting the parallel distance between the contact surface and the original rock surface. On the other hand, this impression reflecting the often convex nature of the contact between boulders and resting platforms, cannot be measured precisely, so Factors of Safety (FoS) computed with this input may have significant uncertainties. Using geometric 3D analysis, here, we present the concept of computing FoS as a function of the impression d, admitting a much more reliable estimate of the actual hazards. Beyond introducing the FoS functions, we also identify all failure modes, some of which have not yet been investigated. We compute the FoS functions for the boulder Pena do Equilibrio, located in Spain. Our computations for FoS against sliding match all earlier results. However, we also compute FoS against toppling and against torsion and show that the latter may be critical. Since our methods are general, this suggests that torsion phenomena, which have been scarcely studied so far, may be relevant to analyze the stability of other natural rock boulders.
Flower symmetry in Saxifraga revisited
Authors: Wiegel Manuel , Lunau Klaus 
Published: February 2023

AbstractMonosymmetry in flowers has evolved many times from ancestors with polysymmetrical flowers. Flower symmetry characteristics often lack intraspecific variability. The genus Saxifraga represents an exception with high variations of floral symmetry between and within species and even within individual plants. Lab-based studies could show that this variation is to some extent caused by the flowers’ response to gravity and thus varies regularly between horizontally and vertically oriented flowers. Here, we investigate inter- and intra-individual variation in flower size, flower colouration, and floral symmetry in three species, Saxifraga stellaris, S. rotundifolia, and S. paniculata. In all three species, the stamen that initiates the sequential stamen movement is mostly downward pointing. In S. stellaris and S. paniculata, the terminal flowers are larger than the other flowers. In S. stellaris and S. rotundifolia, the size of floral guides is larger and the colour is stronger on the upward pointing 3 petals of diagonally and vertically oriented flowers, whereas the other two petals have paler or smaller floral guides. The septum between the two carpels is mostly oriented horizontally. We discuss the evolution of flower monosymmetry in regard to the morphological symmetry referring to symmetry defined by the mirror plane between carpels, petals and moving stamens, and visual symmetry defined by the pollinators view on the floral colour pattern and visible morphological features.
The Long Outer-Hair-Cell RC Time Constant: A Feature, Not a Bug, of the Mammalian Cochlea
Authors: Altoè Alessandro , Shera Christopher A. 
Published: February 2023

AbstractThe cochlea of the mammalian inner ear includes an active, hydromechanical amplifier thought to arise via the piezoelectric action of the outer hair cells (OHCs). A classic problem of cochlear biophysics is that the RC (resistance-capacitance) time constant of the hair-cell membrane appears inconveniently long, producing an effective cut-off frequency much lower than that of most audible sounds. The long RC time constant implies that the OHC receptor potential—and hence its electromotile response—decreases by roughly two orders of magnitude over the frequency range of mammalian hearing, casting doubt on the hypothesized role of cycle-by-cycle OHC-based amplification in mammalian hearing. Here, we review published data and basic physics to show that the “RC problem” has been magnified by viewing it through the wrong lens. Our analysis finds no appreciable mismatch between the expected magnitude of high-frequency electromotility and the sound-evoked displacements of the organ of Corti. Rather than precluding significant OHC-based boosts to auditory sensitivity, the long RC time constant appears beneficial for hearing, reducing the effects of internal noise and distortion while increasing the fidelity of cochlear amplification.
Social relations and exclusion among people facing death
Authors: Seppänen Marjaana , Niemi Mia , Sarivaara Sofia 
Published: February 2023

AbstractIn line with current policies and service developments related to palliative care, more people are dying at home. This situation has provoked discussions about the importance of non-medical issues related to death. The process of dying is often long, with many phases, and the social aspect is a major part of it. Our focus in this article is on dying as a social process. Social relationships are significant and play a meaningful role in enhancing the well-being of older adults approaching the end of life. Meaningful social relationships tend to change over time; however, and the process of dying may exacerbate such changes in and challenge these relationships. The aim of our study was to examine how social relationships are experienced and (re)constructed among older adults (70–83 years old) during the process of dying, in a Finnish context. We were interested in the nature and type of these relationships, and in the possible new forms of expression that may emerge during this process. Our empirical data were based on interviews with seven older adults who were close to death. The analysis revealed processes of exclusion from existing relations. At the same time, we observed new and unexpected relations being initiated, which sometimes became meaningful and supportive. The results highlighted the role of expectations and importance of analysing exclusion from a life-course perspective.
Algal blooms in a river-dominated estuary and nearshore region of Florida, USA: the influence of regulated discharges from water control structures on hydrologic and nutrient conditions
Authors: Phlips E. J. , Badylak S. , Mathews A. L. , Milbrandt E. C. , Montefiore L. R. , Morrison E. S. , Nelson N. , Stelling B. 
Published: February 2023

AbstractFlow-regulated discharges of water from control structures into estuaries result in hydrologic and water chemistry conditions that impact spatial and temporal variability in the structure and biomass of phytoplankton communities, including the potential for harmful algal blooms (HABs). The relationships between regulated Caloosahatchee River (i.e., C-43 Canal) discharges and phytoplankton communities in the Caloosahatchee Estuary and adjacent nearshore regions on the southwest coast of Florida were investigated during two study periods, 2009–2010 and 2018–2019. During periods of low to moderate discharge rates, when mesohaline conditions predominated in the estuary, and water residence times were comparatively long, major blooms of the HAB dinoflagellate speciesAkashiwo sanguineawere observed in the estuary. Periods of high discharge were characterized by comparatively low phytoplankton biomass in the estuary and greater influence of a wide range of freshwater taxa in the upper reaches. By contrast, intense blooms of the toxic dinoflagellateKarenia brevisin the nearshore region outside of the estuary were observed during high discharge periods in 2018–2019. The latter events were significantly associated with elevated levels of nitrogen in the estuary compared to lower average concentrations in the 2009–2010 study period. The relationships observed in this study provide insights into the importance of managing regulated discharge regimes to minimize adverse impacts of HABs on the health of the estuary and related coastal environments.
“We Share All Data with Each Other”: Data-Sharing in Peer-to-Peer Relationships
Authors: Barlösius Eva 
Published: February 2023

AbstractAlthough the topic of data-sharing has boomed in the past few years, practices of datasharing have attracted only scant attention within working groups and scientific cooperation (peer-to-peer data-sharing). To understand these practices, the author draws on Max Weber’s concept of social relationship, conceptualizing data-sharing as social action that takes place within a social relationship. The empirical material consists of interviews with 34 researchers representing five disciplines—linguistics, biology, psychology, computer sciences, and neurosciences. The analysis identifies three social forms of data-sharing in peer-to-peer relationships: (a) closed communal sharing, which is based on a feeling of belonging together; (b) closed associative sharing, in which the participants act on the basis of an agreement; and (c) open associative sharing, which is oriented to “institutional imperatives” (Merton) and to formal regulations. The study shows that far more data-sharing is occurring in scientific practice than seems to be apparent from a concept of open data alone. If the main goal of open-data policy programs is to encourage researchers to increase access to their data, it could be instructive to study the three forms of data-sharing to improve the understanding of why and how scientists make their data accessible to other researchers.
Causality is good for practice: policy design and reverse engineering
Authors: Busetti Simone 
Published: February 2023

AbstractRelevance to practice is an open issue for scholars in public policy and public administration. One major problem is the need to produce knowledge that can guide practitioners designing and implementing public interventions in specific contexts. This article claims that investigating the causal mechanisms of policy programs—i.e., modeling why and how they produce outcomes—can contribute to such knowledge. In this regard, mechanisms offer essential information to guide practitioners when replicating, adjusting, and designing interventions. Unfortunately, not all models of mechanisms can inform practice. The article proposes a strategy for design research and practice inspired by reverse engineering: selecting successful programs, causal modeling, assessing the target context, and designing. Scholars should model mechanisms by identifying the program and non-program elements that contribute to the outcome of interest and abstracting their causal powers. Practitioners can use these models, diagnose their target context, and adjust designs to deal with context-specific problems. The proposed research agenda may enhance orientation to practice and offer a middle ground between the search for abstract, general relationships, and single-case analyses.
Simulation and analysis of high-brightness tapered ridge-waveguide lasers
Authors: Koester Jan-Philipp , Wenzel Hans , Wilkens Martin , Knigge Andrea 
Published: February 2023

AbstractIn this work, a simulation-based analysis of a CW-driven tapered ridge-waveguide laser design is presented. Measurements of these devices delivered high lateral brightness values of $${4}{\hbox {W}\cdot \hbox {mm}^{-1} \hbox {mrad}^{-1}}$$

4

W
·

mm

-
1

mrad

-
1

at $${2.5}\,\hbox {W}$$

2.5

W

optical output power. First, active laser simulations are performed to reproduce these results. Next, the resulting complex valued intra-cavity refractive index distributions are the basis for a modal and beam propagation analysis, which demonstrates the working principle and limitation of the underlying lateral mode filter effect. Finally, the gained understanding is the foundation for further design improvements leading to lateral brightness values of up to $${10}{\hbox {W}\cdot \hbox {mm}^{-1} \hbox {mrad}^{-1}}$$

10

W
·

mm

-
1

mrad

-
1

predicted by simulations.
The Dynamic Strategy of Common Sense Against Radical Revisionism
Authors: Guillon Jean-Baptiste 
Published: February 2023

AbstractCommon-sense philosophers typically maintain that common-sense propositions have a certain kind of epistemic privilege that allows them to evade the threats of skepticism or radical revisionism. Butwhydo they have this special privilege? In response to this question, the “Common-Sense Tradition” contains many different strands of arguments. In this paper, I will develop a strategy that combines two of these strands of arguments. First, the “Dynamic Argument” (or the “starting-point argument”), inspired by Thomas Reid and Charles S. Peirce (but which will be strengthened with the help of Gilbert Harman’s epistemology of belief revision). Second, G.E. Moore’s “greater certainty argument” (interpreted along the lines of Soames’ and Pollock’s construal). This combined strategy, I will argue, is the strong core of Common-Sense Philosophy, and relies on extremely modest and widely held assumptions.
Impacts of COVID-19 on tourism and management response from Banff National Park, Canada
Authors: Geng Christina Dehui , Harshaw Howie W. , Wu Wanli , Wang Guangyu 
Published: February 2023

AbstractThe COVID-19 pandemic posed challenges to the tourism sector globally. We investigated changes in visitor demographics, satisfaction level, and its determinants pre- and peri-COVID-19. Data were collected using questionnaire surveys in 2019 and 2021 within Banff National Park (BNP). The data analyses were based on a sample size of 1183 respondents by conducting factor analysis, correlation analysis and stepwise regression analysis. Results highlight that there were fewer international visitors and more local and domestic visitors during the pandemic. Park attributes were evaluated at a higher satisfaction level peri-COVID-19. The quality of the Park facilities and services were the most important satisfaction determinants pre- and peri-COVID-19, and all the Park COVID-19 measures and actions received positive experience from visitors. This research fills this knowledge gap by developing a better understanding in the change of visitor demographics and satisfaction level in BNP under the context of the pandemic. It also provides implication for both scholars and practitioners to understand the impacts of the pandemic on Park visitation. The study can provide insights for utilizing the pandemic as a transformative strength and for mitigating its negative impact on tourism industry.
PD-L1 immunohistochemistry assay optimization to provide more comprehensive pathological information in classic Hodgkin lymphoma
Authors: Shi Yunfei , Mi Lan , Lai Yumei , Zhao Min , Jia Ling , Du Tingting , Song Yuqin , Li Xianghong 
Published: February 2023

AbstractOverexpression of PD-L1 can be a predictive marker for anti-PD-1 therapeutic efficacy in classic Hodgkin lymphoma (CHL); however, harmonization of different IHC assays remains to be accomplished, and interpretations of PD-L1 immunostaining results remain controversial in CHL. In this study, we sought to optimize the PD-L1 immunohistochemistry (IHC) assay in CHL. All tests were performed on a tumour tissue microarray established from 54 CHL cases. Three IHC antibodies (405.9A11, SP142, 22C3) for detecting PD-L1 expression were compared semi quantitatively with the RNAscope assay (No. 310035, ACD), and the difference in the expression in background immune cells (ICs) between assays and the associations of expression levels with densities of TILs/TAMs were also analysed. 405.9A11 demonstrated best specificity in HRS cells and best sensitivity in ICs. Positive expression of PD-L1 was more frequent in ICs (85.2%) than in HRS cells (48.1%). Different subgroups of background ICs, including tumour-associated macrophages (TAMs), were assessed and scored for CD4, CD8, FOXP3, and CD163 expression. PD-L1 expression on ICs was the factor most associated with the density of TAMs. 405.9A11 provided the most convincing PD-L1 expression results. Pathologists should report PD-L1 expression in a combined manner, including both the status of HRS cells and the percentage of PD-L1-positive ICs.