bluuebunny/crossref_metadata_2025_split huggingface dataset:
Geoheritage and overtourism: a case study from sandstone rock cities in the Czech Republic
Authors: Drápela Emil 
Published: October 2022

Abstract
Sandstone districts are among the most visited and popular geosites in the Czech Republic. Unfortunately, they are often affected by the harmful effects of mass tourism, referred to as overtourism. Sandstone geosites are very vulnerable owing to the rock's relative softness, and large numbers of visitors can be a threat to them as they accelerate the intensity of their degradation. The overtourism situation then brings other negatives not only to the geosites but also to their surroundings. This paper describes the reasons for the overtourism situation in Czech rock cities, the effects of overtourism on geosites and communities living in their vicinity, and possible solutions from the perspective of nature conservation and tourism management. The data come from field observations, interviews, and publicly available data on the development of the number of visitors to tourist destinations. The results showed that overtourism is a widespread problem in the Czech rock cities, damaging these geosites and negatively affecting the residents of the surrounding villages. In addition, it is necessary to act quickly because the number of visitors to these geosites is continuing to grow in the long term. The article proposes three measures that should mitigate the harmful effects of mass tourism: communication with the visitors, destination management and the protection of geosites. However, for these measures to work, a strategy must be developed that will be respected by all of the main actors in the local tourism industry, and these measures should be targeted at specific problems. This example is typical of the general problems encountered in any geotourism site, and such remedial strategies provide an example of what could be applied to avoid problems elsewhere.
Oncogenic Merkel Cell Polyomavirus T Antigen Truncating Mutations are Mediated by APOBEC3 Activity in Merkel Cell Carcinoma
Authors: Soikkeli Anni I. , Kyläniemi Minna K. , Sihto Harri , Alinikula Jukka 
Published: October 2022

Merkel cell carcinoma (MCC) is an aggressive skin cancer, which is frequently caused by Merkel cell polyomavirus (MCPyV). Mutations of MCPyV tumor (T) antigens are major pathologic events of virus-positive (MCPyV+) MCCs, but their source is unclear. Activation-induced cytidine deaminase (AID)/APOBEC family cytidine deaminases contribute to antiviral immunity by mutating viral genomes and are potential carcinogenic mutators. We studied the contribution of AID/APOBEC cytidine deaminases to MCPyV large T (LT) truncation events. The MCPyV LT area in MCCs was enriched with cytosine-targeting mutations, and a strong APOBEC3 mutation signature was observed in MCC sequences. AICDA and APOBEC3 expression were detected in the Finnish MCC sample cohort, and LT expression correlated with APOBEC3H and APOBEC3G. Marginal but statistically significant somatic hypermutation targeting activity was detected in the MCPyV regulatory region. Our results suggest that APOBEC3 cytidine deaminases are a plausible cause of the LT truncating mutations in MCPyV+ MCC, while the role of AID in MCC carcinogenesis is unlikely.Significance:We uncover APOBEC3 mutation signature in MCPyV LT that reveals the likely cause of mutations underlying MCPyV+ MCC. We further reveal an expression pattern of APOBECs in a large Finnish MCC sample cohort. Thus, the findings presented here suggest a molecular mechanism underlying an aggressive carcinoma with poor prognosis.
Clinical Prediction Model for Antibody-Mediated Rejection: A Strategy to Minimize Surveillance Endomyocardial Biopsies After Heart Transplantation
Authors: Coutance Guillaume , Kransdorf Evan , Aubert Olivier , Bonnet Guillaume , Yoo Daniel , Rouvier Philippe , Duong Van Huyen Jean-Paul , Bruneval Patrick , Taupin Jean-Luc , Leprince Pascal , Varnous Shaida , Kobashigawa Jon , Jouven Xavier , Patel Jignesh , Loupy Alexandre 
Published: October 2022

Background:
In heart transplantation, antibody-mediated rejection (AMR) is a major contributor to patient morbidity and mortality. Multiple routine endomyocardial biopsies (EMB) remain the gold standard to detect AMR, but this invasive procedure suffers from many limitations. We aimed to develop and validate an AMR risk model to improve individual risk stratification of AMR.

Methods:
Heart recipients from 2 referral transplant centers, Cedars-Sinai (US) and Pitié-Salpêtrière (France), were included from 2012 to 2019. Database included detailed clinical, immunologic, imaging, and histological parameters. The US cohort was randomly distributed in a derivation (2/3) and in a test set (1/3). The primary end point was biopsy-proven AMR. A mixed effect logistic regression model with a random intercept was applied to identify variables independently associated with AMR. Simulation analyzes were performed.

Results:

The US and French cohorts comprised a total of 1341 patients, representing 12 864 EMB. Overall, 490 AMR episodes were diagnosed (3.8% of EMB). Among the 26 potential determinants of AMR, 5 variables showed independent association: time post-transplant (
P
<0.001), pretransplant sensitizing event (
P
=0.001), circulating donor-specific anti–human leukocyte antigen antibody (
P
=0.001), graft dysfunction (
P
=0.004), and prior history of definite AMR (
P
<0.001). In the US test set, the calibration and the discrimination of the model were accurate (area under the curve, 0.79 [95% CI, 0.78–0.81]). Those results were confirmed in the external validation cohort (area under the curve, 0.78 [95% CI, 0.77–0.79]) and reinforced by various sensitivity analyses. The model also showed good performance to predict overall cause of rejection. Simulation models revealed that the AMR risk model could safely reduce the number of EMB.

Conclusions:
Our results support the use of the AMR risk model as a clinical decision tool to minimize the number of routine EMB after heart transplantation.
PHB2 Maintains the Contractile Phenotype of VSMCs by Counteracting PKM2 Splicing
Authors: Jia Yiting , Mao Chenfeng , Ma Zihan , Huang Jiaqi , Li Wenqiang , Ma Xiaolong , Zhang Siting , Li Meihong , Yu Fang , Sun Yingying , Chen Jingzhou , Feng Juan , Zhou Yuan , Xu Qingbo , Zhao Ling , Fu Yi , Kong Wei 
Published: October 2022

Background:
Phenotypic transition of vascular smooth muscle cells (VSMCs) accounts for the pathogenesis of a variety of vascular diseases during the early stage. Recent studies indicate the metabolic reprogramming may be involved in VSMC phenotypic transition. However, the definite molecules that link energy metabolism to distinct VSMC phenotype remain elusive.

Methods:
A carotid artery injury model was used to study postinjury neointima formation as well as VSMC phenotypic transition in vivo. RNA-seq analysis, cell migration assay, collagen gel contraction assay, wire myography assay, immunoblotting, protein interactome analysis, co-immunoprecipitation, and mammalian 2-hybrid assay were performed to clarify the phenotype and elucidate the molecular mechanisms.

Results:

We collected cell energy-regulating genes by using Gene Ontology annotation and applied RNA-Seq analysis of transforming growth factor-β or platelet-derived growth factor BB stimulated VSMCs. Six candidate genes were overlapped from energy metabolism-related genes and genes reciprocally upregulated by transforming growth factor-β and downregulated by platelet-derived growth factor BB. Among them, prohibitin 2 has been reported to regulate mitochondrial oxidative phosphorylation. Indeed, prohibitin 2-deficient VSMCs lost the contractile phenotype as evidenced by reduced contractile proteins. Consistently,

Phb2
SMCKO

mice were more susceptible to postinjury VSMC proliferation and neointima formation compared with

Phb2
flox/flox

mice. Further protein interactome analysis, co-immunoprecipitation, and mammalian 2-hybrid assay revealed that prohibitin 2, through its C-terminus, directly interacts with hnRNPA1, a key modulator of pyruvate kinase M1/2 (PKM) mRNA splicing that promotes PKM2 expression and glycolysis. Prohibitin 2 deficiency facilitated PKM1/2 mRNA splicing and reversion from PKM1 to PKM2, and enhanced glycolysis in VSMCs. Blocking prohibitin 2–hnRNPA1 interaction resulted in increased PKM2 expression, enhanced glycolysis, repressed contractile marker genes expression in VSMCs, as well as aggravated postinjury neointima formation in vivo.

Conclusions:
Prohibitin 2 maintains VSMC contractile phenotype by interacting with hnRNPA1 to counteract hnRNPA1-mediated PKM alternative splicing and glucose metabolic reprogramming.
Shock and Awe: Medieval Northern European Jews and the Language of Violence
Authors: Barzilay Tzafrir 
Published: October 2022

Abstract
In twelfth-century northern Europe, public declarative violence was often employed to establish and demonstrate authority, lordship and power. This article argues that Jews adopted the Christian language of violence but reshaped it to communicate their own views and culture. The first section focuses on depictions of public violence during the persecution of the First Crusade, and on changes in Jewish liturgical practices supported by violent narratives. It shows that during the twelfth century, these descriptions became blunter and more evocative, and were established as a major feature of Jewish culture. The second section analyses the place of declarative public violence in contemporary Christian culture, while comparing it to Jewish perceptions on this issue. It shows that Jews saw such violence as major means to prove loyalty to their identity, to communicate their values and to claim authority.
Creating an Enhanced Infrastructure of Parliamentary Archives for Better Democratic Transparency and Legislative Research
Authors: Kiss Rebeka , Sebők Miklós 
Published: October 2022

Abstract
In this paper, we summarise the key findings of the forum “Data4Parliaments” Parliamentary Data for a Better Democracy, organised by the OPTED network at the European Parliament on 15 June 2022. The aim of the conference was to provide a forum for the exchange of ideas related to sharing and analysing parliamentary text data between official archives and different user groups from the social sciences and the civil society.
Is Indigeneity Discourse Productive for the Cause of Preserving Armenian Cultural Heritage?
Authors: Maghakyan Simon 
Published: October 2022

Abstract
The indigenous status of Armenian people has recently become a common declaration in online Armenian spaces. While factually correct, it is imperative to assess whether a more pronounced indigenous identity can help to resolve the existential issue of preserving the tangible heritage of Armenians, which has now been threatened politically. Through dissecting various topics related to indigenous peoples’ issues, this essay argues that affirmative indigeneity discourse – instead of one exclusively linked with historic victimhood and historical superiority – can be beneficial to preservation, though the risks are likely higher.
Processes Contributing to North American Cold Air Outbreaks Based on Air Parcel Trajectory Analysis
Authors: Hartig Kara , Tziperman Eli , Loughner Christopher P. 
Published: October 2022

Abstract
Wintertime cold air outbreaks are periods of extreme cold, often persisting for several days and spanning hundreds of kilometers or more. They are commonly associated with intrusions of cold polar air into the midlatitudes, but it is unclear whether the air mass’s initial temperature in the Arctic or its cooling as it travels is the determining factor in producing a cold air outbreak. By calculating air parcel trajectories for a preindustrial climate model scenario, we study the role of the origin and evolution of air masses traveling over sea ice and land and resulting in wintertime cold air outbreaks over central North America. We find that not all Arctic air masses result in a cold air outbreak when advected into the midlatitudes. We compare trajectories that originate in the Arctic and result in cold air outbreaks to those that also originate in the Arctic but lead to median temperatures when advected into the midlatitudes. While about one-third of the midlatitude temperature difference can be accounted for by the initial height and temperature in the Arctic, the other two-thirds are a result of differences in diabatic heating and cooling as the air masses travel. Vertical mixing of cold surface air into the air mass while it travels dominates the diabatic cooling and contributes to the cold events. Air masses leading to cold air outbreaks experience more negative sensible heat flux from the underlying surface, suggesting that preconditioning to establish a cold surface is key to producing cold air outbreaks.

Significance Statement
Wintertime cold air outbreaks can cause temperatures to plummet tens of degrees below freezing over the northern United States, with the potential to damage agriculture, infrastructure, and human health. Accurate predictions under climate change could help mitigate these effects, but there is disagreement over whether cold air outbreaks have declined in line with the already-observed global warming trend or persisted in spite of it. Focusing on cold air outbreaks that originate from the Arctic, we find that there must be additional cooling of the traveling air mass by mixing with very cold surface air as it moves south over North America in order to result in a cold outbreak.
Interannual Variations of the β Drift of Tropical Cyclones over the Western North Pacific
Authors: Lu Jun , Wu Liguang , Zhou Shunwu , Zhao Haikun 
Published: October 2022

Abstract
Tropical cyclone (TC) movement consists essentially of the large-scale environmental steering and the β drift, and the latter is also affected by large-scale environmental flows. However, few previous studies have been conducted to examine the interannual variations of the β drift of TCs in the western North Pacific (WNP) basin and the corresponding relationship with the large-scale environmental flow. Using the observed TC tracks and reanalysis dataset during 1965–2019, it is found that the β drift plays a more important role in the TC motion than environmental steering at the interannual time scale. The westward (northward) component of the β drift in the environment with anticyclonic relative vorticity is slower (faster) than that with cyclonic relative vorticity, while an equatorward (poleward) relative vorticity gradient decreases (increases) the westward component of the β drift, in agreement with previous numerical simulations. It is also found that the southwestward migration of the WNP subtropical high can decrease (increase) the westward (northward) component of the β drift. This study suggests that environmental influence on the β drift should be considered when understanding interannual variations of TC movement and tracks, which are important to TC landfall, emergency management, and hazard mitigation.

Significance Statement
The β drift is an important component of TC movement and is affected by large-scale environmental flows. However, few previous studies have been conducted to examine the interannual variations of the β drift of TCs in the western North Pacific basin and the corresponding relationship with the large-scale environmental flow. This study finds that the β drift plays a more important role in the TC motion than environmental steering at the interannual time scale, and the interannual variations of the β drift are also controlled by large-scale environmental flows. It is suggested that environmental influence on the β drift should be considered when understanding interannual variations of TC movement and tracks, which are important to TC landfall, emergency management, and hazard mitigation.
Global Observing System Experiments within the Météo-France 4D-Var Data Assimilation System
Authors: Chambon P. , Mahfouf J.-F. , Audouin O. , Birman C. , Fourrié N. , Loo C. , Martet M. , Moll P. , Payan C. , Pourret V. , Raspaud D. 
Published: October 2022

Abstract
Observing system experiments were undertaken within the 4D-Var data assimilation of the Météo-France global numerical weather prediction (NWP) model. A 6-month period was chosen (October 2019–March 2020) where 40 million observations per day were assimilated. The importance of in situ observations provided by aircraft, radiosondes, and surface weather stations, despite their small fractional amount (7%), has been confirmed particularly in the Northern Hemisphere. Moreover, the largest impact over Europe in terms of root-mean-square error (RMSE) scores comes from surface observations. Satellite data play a dominant role over tropical regions and the Southern Hemisphere. Microwave radiances have a more pronounced impact on the long range and on the humidity field than infrared radiances, despite being less numerous (10% versus 80%). Bending angles impact significantly the quality of the upper-troposphere–lower-stratosphere temperature of the tropics and Southern Hemisphere. Atmospheric motion vectors (AMVs) are beneficial in wind forecasts at low and high levels in the tropics and the Southern Hemisphere, but also in the humidity field. Such impacts are only significant during the first 48 h of the forecasts. Scatterometer winds have an impact restricted to low levels that is kept at longer ranges. A comparison with forecast sensitivity–observation impact studies over a 3-month period using the same measure of short-range (24-h) forecast errors reveals that the ranking between the major observing systems is kept between these two ways of measuring observation impact in NWP. From our conclusions, recommendations are provided on possible evolutions of the global observing system for NWP.
A Descriptive Overview of Mental Health Services Offered in Post-Secondary Educational Institutions Across Canada
Authors: Read Alana , Lutgens Danyael , Malla Ashok 
Published: October 2022

Objective Access to adequate mental health (MH) services is necessary for nearly half of Canadian youth (18–24 years) who enroll in post-secondary education given the relatively high risk of MH problems. Our objectives were to determine the status of MH services available to students in post-secondary institutions in Canada and to determine the extent to which these services are based on the principles of a high-quality youth MH (YMH) service. Method Information on MH services was collected from websites of a representative sample ( N = 67) of post-secondary institutions across all provinces. Data were analysed descriptively according to four categories (universities with a Faculty of Medicine (FoM) n = 18, other large universities n = 15, small universities n = 16, and colleges n = 18). Results Most institutions provided 24-h crisis line support (84%) and indicated the availability of free counselling or psychotherapy ( n = 62 of 67, 92.5%), while only a minority indicated provision of an initial clinical assessment (25%) and provision of multiple sessions of therapy (37%). Wait time for first contact was impressively low (<72 h) in the minority of institutions (40%) which provided this information. Access to either a prescribing physician or psychiatrist was infrequent, though several mentioned an unexplained model of “stepped care” and outside referrals. While relevant information was not uniformly easy to access, larger institutions both with and without a FoM appear to be better poised to provide MH services. None of the institutions appeared to follow all the principles of service delivery recommended for a high-quality YMH, with only two showing early identification activities. Conclusions MH services in post-secondary institutions may need a transformation similar to YMH services, including a clear pathway to care, an initial clinical assessment, early identification of MHA disorders, and better utilization of institutional resources through greater collaboration and matching of timely interventions to the presenting problems.
Ameliorative effect of herbacetin against cyclophosphamide-induced nephrotoxicity in rats via attenuation of oxidative stress, inflammation, apoptosis and mitochondrial dysfunction
Authors: Ijaz Muhammad Umar , Mustafa Shama , Batool Riffat , Naz Huma , Ahmed Hussain , Anwar Haseeb 
Published: October 2022

Herbacetin (HBN) is a glycosylated flavonoid, which possesses numerous pharmacological properties. Cyclophosphamide (CYC) is a chemotherapeutic drug that adversely affects the kidneys. The present investigation aimed to evaluate the curative potential of HBN against CYC-induced nephrotoxicity. Sprague Dawley rats ( n = 48) were randomly divided into four groups: control (0.1% DMSO + food), CYC (150 mg/kg b.wt.), CYC+HBN (150 + 40 mg/kg b.wt.), and HBN (40mg/kg b.wt.). CYC treatment significantly decreased the activities of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GSR) while elevating the concentration of reactive oxygen species (ROS) and malondialdehyde (MDA). Treatment with HBN significantly recovered the activity of CAT, SOD, GPx, and GSR while reducing the concentrations of ROS and MDA. Moreover, an increase in the level of renal functional markers, including Urea, creatinine, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL), and a decrease in creatinine clearance after CYC administration was recovered to control values by HBN treatment. Furthermore, HBN treatment normalized the increased levels of inflammatory markers such as nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) after CYC administration. Besides, HBN administration increased the expression of anti-apoptotic markers (Bcl-2) while decreasing the apoptotic markers (Bax and Caspase-3). Furthermore, HBN decreased the activities of tricarboxylic acid (TCA) cycle enzymes (ICDH, αKGDH, SDH, and MDH) as well as renal mitochondrial respiratory-chain complexes (I-IV) and repolarized mitochondrial membrane potential (ΔΨm). Additionally, HBN administration significantly protected against renal histological damage induced by CYC. In conclusion, CYC-induced toxicity was effectively ameliorated by the HBN administration. These results indicate that HBN might be considered as a potential protective agent against nephrotoxicity. The observed protection may be due to its antioxidant, anti-inflammatory, and anti-apoptotic potential.