bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cognitive practice effects delay diagnosis of MCI: Implications for clinical trials
Authors: Sanderson‐Cimino Mark , Elman Jeremy A. , Tu Xin M. , Gross Alden L. , Panizzon Matthew S. , Gustavson Daniel E. , Bondi Mark W. , Edmonds Emily C. , Eglit Graham M.L. , Eppig Joel S. , Franz Carol E. , Jak Amy J. , Lyons Michael J. , Thomas Kelsey R. , Williams McKenna E. , Kremen William S. ,   Alzheimer's Disease Neuroimaging Initiative
Published: February 2022

AbstractIntroductionPractice effects (PEs) on cognitive tests obscure decline, thereby delaying detection of mild cognitive impairment (MCI). Importantly, PEs may be present even when there are performance declines, if scores would have been even lower without prior test exposure. We assessed how accounting for PEs using a replacement‐participants method impacts incident MCI diagnosis.MethodsOf 889 baseline cognitively normal (CN) Alzheimer's Disease Neuroimaging Initiative (ADNI) participants, 722 returned 1 year later (mean age = 74.9 ± 6.8 at baseline). The scores of test‐naïve demographically matched “replacement” participants who took tests for the first time were compared to returnee scores at follow‐up. PEs—calculated as the difference between returnee follow‐up scores and replacement participants scores—were subtracted from follow‐up scores of returnees. PE‐adjusted cognitive scores were then used to determine if individuals were below the impairment threshold for MCI. Cerebrospinal fluid amyloid beta, phosphorylated tau, and total tau were used for criterion validation. In addition, based on screening and recruitment numbers from a clinical trial of amyloid‐positive individuals, we estimated the effect of earlier detection of MCI by accounting for cognitive PEs on a hypothetical clinical trial in which the key outcome was progression to MCI.ResultsIn the ADNI sample, PE‐adjusted scores increased MCI incidence by 19% (P < .001), increased proportion of amyloid‐positive MCI cases (+12%), and reduced proportion of amyloid‐positive CNs (–5%; P’s < .04). Additional calculations showed that the earlier detection and increased MCI incidence would also substantially reduce necessary sample size and study duration for a clinical trial of progression to MCI. Cost savings were estimated at ≈$5.41 million.DiscussionDetecting MCI as early as possible is of obvious importance. Accounting for cognitive PEs with the replacement‐participants method leads to earlier detection of MCI, improved diagnostic accuracy, and can lead to multi‐million‐dollar cost reductions for clinical trials.
Diet‐induced Alzheimer's‐like syndrome in the rabbit
Authors: Weiss Craig , Bertolino Nicola , Procissi Daniele , Aleppo Grazia , Smith Quinn C. , Viola Kirsten L. , Bartley Samuel C. , Klein William L. , Disterhoft John F. 
Published: February 2022

AbstractIntroductionAlthough mouse models of Alzheimer's disease (AD) have increased our understanding of the molecular basis of the disease, none of those models represent late‐onset Alzheimer's Disease which accounts for >90% of AD cases, and no therapeutics developed in the mouse (with the possible exceptions of aduhelm/aducanumab and gantenerumab) have succeeded in preventing or reversing the disease. This technology has allowed much progress in understanding the molecular basis of AD. To further enhance our understanding, we used wild‐type rabbit (with a nearly identical amino acid sequence for amyloid as in humans) to model LOAD by stressing risk factors including age, hypercholesterolemia, and elevated blood glucose levels (BGLs), upon an ε3‐like isoform of apolipoprotein. We report a combined behavioral, imaging, and metabolic study using rabbit as a non‐transgenic model to examine effects of AD‐related risk factors on cognition, intrinsic functional connectivity, and magnetic resonance‐based biomarkers of neuropathology.MethodsAging rabbits were fed a diet enriched with either 2% cholesterol or 10% fat/30% fructose. Monthly tests of novel object recognition (NOR) and object location memory (OLM) were administered to track cognitive impairment. Trace eyeblink conditioning (EBC) was administered as a final test of cognitive impairment. Magnetic resonance imaging (MRI) was used to obtain resting state connectivity and quantitative parametric data (R2*).ResultsExperimental diets induced hypercholesterolemia or elevated BGL. Both experimental diets induced statistically significant impairment of OLM (but not NOR) and altered intrinsic functional connectivity. EBC was more impaired by fat/fructose diet than by cholesterol. Whole brain and regional R2* MRI values were elevated in both experimental diet groups relative to rabbits on the control diet.DiscussionWe propose that mechanisms underlying LOAD can be assessed by stressing risk factors for inducing AD and that dietary manipulations can be used to assess etiological differences in the pathologies and effectiveness of potential therapeutics against LOAD. In addition, non‐invasive MRI in awake, non‐anesthetized rabbits further increases the translational value of this non‐transgenic model to study AD.
Genome-Wide Mapping and Microscopy Visualization of Protein–DNA Interactions by pA-DamID
Authors: van Schaik Tom , Manzo Stefano G. , van Steensel Bas 
Published: February 2022

AbstractSeveral methods have been developed to map protein–DNA interactions genome-wide in the last decades. Protein A-DamID (pA-DamID) is a recent addition to this list with distinct advantages. pA-DamID relies on antibody-based targeting of the bacterial Dam enzyme, resulting in adenine methylation of DNA in contact with the protein of interest. This m6A can then be visualized by microscopy, or mapped genome-wide. The main advantages of pA-DamID are an easy and direct visualization of DNA that is in contact with the protein of interest, unbiased mapping of protein–DNA interactions, and the possibility to select specific subpopulations of cells by flow cytometry before further sample processing. pA-DamID is particularly suited to study proteins that form large chromatin domains or that are part of distinct nuclear structures such as the nuclear lamina. This chapter describes the pA-DamID procedure from cell harvesting to the preparation of microscopy slides and high-throughput sequencing libraries.
Renormalization of the axial current operator in dimensional regularization at four-loop in QCD
Authors: Chen Long , Czakon Michał 
Published: February 2022

Abstract
We provide the renormalization constants of the axial current operators, both singlet and non-singlet, in dimensional regularization up to four-loop order in (QCD), determined using the off-shell Ward-Takahashi identity for an axial current with a non-anticommuting γ5. A possible application of the result for the singlet axial current operator is the extraction of the non-decoupling mass logarithms in the axial quark form factors.
Uncovering clinical and radiological asymmetry in progressive supranuclear palsy—Richardson’s syndrome
Authors: Picillo Marina , Tepedino Maria Francesca , Abate Filomena , Ponticorvo Sara , Erro Roberto , Cuoco Sofia , Oksuz Nevra , Di Salle Gianfranco , Di Salle Francesco , Esposito Fabrizio , Pellecchia Maria Teresa , Manara Renzo , Barone Paolo 
Published: February 2022

Abstract
Background
Richardson’s syndrome (RS) is considered the most symmetric phenotype of progressive supranuclear palsy (PSP) as opposed to PSP with predominant corticobasal syndrome (PSP-CBS) or parkinsonism (PSP-P).

Objectives
Evaluate asymmetrical motor and higher cortical features in probable PSP-RS and compare the degree of asymmetry of cortical lobes and hemispheres between PSP-RS, PSP-CBS, PSP-P, and age-matched healthy controls (HC).

Methods
Asymmetry of motor and higher cortical features evaluated with an extensive videotaped neurologic examination was investigated in 28 PSP-RS, 8 PSP-CBS, and 14 PSP-P. Brain MRI to compute the laterality index (LI) was performed in 36 patients as well as in 56 HC.

Results
In PSP-RS, parkinsonism was the most common asymmetric motor feature (53.6%), followed by dystonia and myoclonus (21.4% and 17.9%, respectively). Among higher cortical features, limb apraxia was found asymmetric in about one-third of patients. PSP-RS disclosed higher LI for hemispheres compared to HC, indicating a greater degree of asymmetry (p = 0.003). The degree of asymmetry of clinical features was not different between PSP-RS and those qualifying for PSP-CBS or PSP-P. As for imaging, LI was not different between PSP-RS, PSP-CBS, and PSP-P in any cortical region.

Conclusions
Motor and higher cortical features are asymmetric in up to 50% of PSP-RS who also present a greater degree of asymmetry in hemispheres compared to age-matched HC. Lateralization of clinical features should be annotated in PSP.
A horizontal Chern–Gauss–Bonnet formula on totally geodesic foliations
Authors: Baudoin Fabrice , Grong Erlend , Vega-Molino Gianmarco 
Published: February 2022

AbstractUnder suitable conditions, we show that the Euler characteristic of a foliated Riemannian manifold can be computed only from curvature invariants which are transverse to the leaves. Our proof uses the hypoelliptic sub-Laplacian on forms recently introduced by two of the authors in Baudoin and Grong (Ann Glob Anal Geom 56(2):403–428, 2019).
Bidirectional energy-based pushover procedure as a fast approach to establish approximate IDA curves under biaxial seismic excitations: an evaluation for medium- and high-rise buildings
Authors: Soleimani Sahman , Moghadam Abdolreza S. , Aziminejad Armin 
Published: February 2022

AbstractThis paper evaluates the accuracy of bidirectional energy-based pushover (BEP) procedure in predicting approximate incremental dynamic analysis (IDA) results for medium- and high-rise structures. BEP provides approximate IDA curves under the simultaneous effect of the two horizontal components of ground motions and is applicable to both symmetric- and asymmetric-plan buildings. The method has already proven useful in low-rise buildings, and this study aims to evaluate its suitability for mid- and high-rise structures. Six steel structures were considered in this evaluation in two groups of 9- and 20-story buildings, with each group consisting of a symmetric, a one-way asymmetric, and a two-way asymmetric-plan building. The assessment was performed for 22 pairs of far-field ground motion records. The results revealed that the accuracy of the method was satisfactory to produce approximate IDA curves for all structural models. The method had similar accuracy in the asymmetric models as it did in the symmetric models, although the accuracy showed a tendency to decrease as the height of the building increased. BEP also provided reasonable estimates of the demands in both 'flexible' and 'stiff sides' of the asymmetric buildings as well as the demands over the height of the buildings.
To have or not to have: expression of amino acid transporters during pathogen infection
Authors: Tünnermann Laura , Colou Justine , Näsholm Torgny , Gratz Regina 
Published: February 2022

AbstractThe interaction between plants and plant pathogens can have significant effects on ecosystem performance. For their growth and development, both bionts rely on amino acids. While amino acids are key transport forms of nitrogen and can be directly absorbed from the soil through specific root amino acid transporters, various pathogenic microbes can invade plant tissues to feed on different plant amino acid pools. In parallel, plants may initiate an immune response program to restrict this invasion, employing various amino acid transporters to modify the amino acid pool at the site of pathogen attack. The interaction between pathogens and plants is sophisticated and responses are dynamic. Both avail themselves of multiple tools to increase their chance of survival. In this review, we highlight the role of amino acid transporters during pathogen infection. Having control over the expression of those transporters can be decisive for the fate of both bionts but the underlying mechanism that regulates the expression of amino acid transporters is not understood to date. We provide an overview of the regulation of a variety of amino acid transporters, depending on interaction with biotrophic, hemibiotrophic or necrotrophic pathogens. In addition, we aim to highlight the interplay of different physiological processes on amino acid transporter regulation during pathogen attack and chose the LYSINE HISTIDINE TRANSPORTER1 (LHT1) as an example.
The role of occlusion and micro-incontinence in the pathogenesis of penile lichen sclerosus: an observational study of pro-inflammatory cytokines’ gene expression
Authors: Czajkowski M. , Wierzbicki P. , Kotulak-Chrząszcz A. , Czajkowska K. , Bolcewicz M. , Kłącz J. , Kreft K. , Lewandowska A. , Nedoszytko B. , Sokołowska-Wojdyło M. , Kmieć Z. , Kalinowski L. , Nowicki R. J. , Matuszewski M. 
Published: February 2022

Abstract
Purpose
To assess the expression of selected cytokines in penile lichen sclerosus (PLS) and associate them with the occurrence of micro-incontinence (MI) in different stages of PLS.

Methods
The skin biopsies from 49 PLS affected, and 13 from nonlesional foreskins (healthy control adult males undergoing circumcision due to phimosis caused by short frenulum) were obtained. All specimens were used for RNA extraction and RT-qPCR. Quantitative assessment of the gene expression of interleukin 1-A (IL-1A), interleukin 1-B (IL-1B), interleukin 1 receptor antagonist (IL-1RN), interleukin 6 (IL-6), transforming growth factor β1 (TGF-β1), and interferon-gamma (INF-γ) was performed. To determinate the presence of MI, the patients were asked about voiding patterns, especially leaking tiny drops of urine from the urethral meatus after urination.

Results
IL-1A, IL-6, and INF-γ mRNA levels were approximately 150, 16, and 59 times higher in PLS than in control samples, respectively. The highest IL-1A mRNA levels were observed in early PLS (n = 13), INF-γ in moderate PLS (n = 32), while IL-6 in severe PLS (n = 4). MI was noted in 45 PLS patients vs. 0 in control (p < 0.0001). IL-1A and IL-6 vs control ratios were concentration (ca.) 400 and 30 times higher, respectively, in MI PLS samples than in PLS without MI.

Conclusion
Occlusion and irritating urine effect are associated with the clinical progression of penile LS with increased mRNA expression of IL-1A, INF-γ, and IL-6 pro-inflammatory cytokines in the foreskin.
Evaluating ecosystem services for agricultural wetlands: a systematic review and meta-analysis
Authors: Eric Asare , Chrystal Mantyka-Pringle , Erik Anderson , Kenneth Belcher , Robert Clark 
Published: February 2022

AbstractGlobally, the extent of inland wetlands has declined by approximately 70% since the start of the twentieth century, resulting in the loss of important wetland-associated ecosystem services. We evaluate the drivers of wetland values in agricultural landscapes to increase the effectiveness and reliability of benefit transfer tools to assign values to local wetland services. We reviewed 668 studies that analyzed wetland ecosystem services within agricultural environments and identified 45 studies across 22 countries that provided sufficient economic information to be included in a quantitative meta-analysis. We developed meta-regression models to represent provisioning and regulating wetland ecosystem services and identify the main drivers of these ecosystem service categories. Provisioning wetland ecosystem service values were best explained (direction of effects in parenthesis) by high-income variable (+), peer-reviewed journal publications (+), agricultural total factor productivity index (−) and population density (+), while agricultural total factor productivity index (−), income level ( +) and wetland area (−) had significant effects on regulating wetland ecosystem service values. Our models can help estimate wetland values more reliably across similar regions because they have significantly lower transfer errors (66 and 185% absolute percentage error for the provisioning and regulating models, respectively) than the errors from unit value transfers. Model predicted wetland values ($/Ha/Year) range from $0.62 to $11,216 for regulating services and $0.95 to $2,122 for provisioning services and vary based on the differences in the levels of the variables (in the wetland locations) that best explained the estimated models.
The Holship ruling of the ECtHR and the protection of fundamental rights in Europe
Authors: Graver Hans Petter 
Published: February 2022

AbstractThe status of trade union rights in the EU has been contentious since the CJEU sent shockwaves through the trade unions of Europe in December 2007 with its rulings in the cases of Viking and Laval. In its recent Holship ruling, the ECtHR has challenged these rulings. Contrary to the assertion of the CJEU in Laval that it is inherent in the very exercise of trade union rights and the right to take collective action that they will be prejudiced to a certain degree, the ECtHR stated that “the degree to which a collective action risks having economic consequences cannot (…) in and of itself be a decisive consideration in the analysis of proportionality under Article 11”. This has potentially wide-reaching implications for the relationship between the human rights recognized in international human rights conventions and EU fundamental rights.
An intriguing find of an early Middle Pleistocene European snow leopard, Panthera uncia pyrenaica ssp. nov. (Mammalia, Carnivora, Felidae), from the Arago cave (Tautavel, Pyrénées-Orientales, France)
Authors: Hemmer Helmut 
Published: February 2022

Abstract
A complete mandible of a leopard-sized cat from the early Middle Pleistocene Arago cave MIS 14 level (Tautavel, France) was at first assigned to the snow leopard, Pantherauncia. A subsequent comprehensive description and analysis found the mandibular corpus snow leopard-like, but interpreted the dentition more like the leopard, Pantherapardus. Thus, this cat was classified as P.pardus. The re-study given in this paper presents the key to its real evolutionary place. The extant snow leopard is characterised by an autapomorphic excessively large dentition, not found in any other Panthera species. The Arago specimen represents the symplesiomorphic small-tooth type. Subtracting this character leaves diagnostic uncertainty, when only looking at the teeth, but provides an unambiguous P. uncia assignment when looking for the unique factor combination of the mandibular corpus. We deal with an ancestral snow leopard who demonstrates that the later large dentition was not yet evolved in the early Middle Pleistocene. An abstract heading in a symposium program book proposed the name Pantherapardustautavelensis nov. ssp., not available by the International Code of Zoological Nomenclature. Therefore, the Arago snow leopard is named Pantheraunciapyrenaica ssp. nov. A single Pantherauncia record in the Eurasian late Middle Pleistocene from Zhoukoudian Locality 3 (China) perfectly bridges the difference between the Arago cat and the extant snow leopard. The early Middle Pleistocene European history of leopard-sized cats was originally understood as a more or less uniform development within the species P.pardus. This turns out to be a repeated replacement of different species and subspecies, involving Pumapardoides, Pantherapardus and Pantherauncia. It cannot even be excluded that snow leopards returned in each intense cold period of the Middle and Late Pleistocene from their Central Asian home to Europe.
Fabrication of Thin Walls with and without Close Loop Control as a Function of Scan Strategy Via Direct Energy Deposition
Authors: Ali Nashit , Tomesani Luca , Ascari Alessandro , Fortunato Alessandro 
Published: February 2022

AbstractDirect Energy Deposition (DED) is a technique used to fabricate metallic parts and is a subcategory of metal additive manufacturing. Despite of its vast advantages over traditional manufacturing the deployment at industrial level is still limited due to underlaying concerns of process stability and repeatability. In-situ monitoring, therefore, is indispensable while depositing via DED. The present experiment is a step towards enhancing our current understanding of the DED when coupled with a closed loop control system to control melt pool width for deposition of thin-walled structures, and as a function of scan strategy. 316L stainless steel powder was deposited on S235JR substrate. A total of 6 iterations are reported, out of many performed, of which 3 were without the closed loop control. Also, to understand the effect of scan strategy as a function of laser power. Two different scan strategies were employed for understanding of the issue i.e., unidirectional, and bidirectional. Apart from the geometrical consistency of the wall, microhardness, density calculations and microstructure were investigated. The geometric consistency was found to be almost perfect with the bidirectional scan strategy. In case of unidirectional scan strategy, the wall shows a negative slope along the other extreme regardless of the closed loop control system. Dilution zone shows the hardness greater than both the substrate and the wall. The specimens fabricated without the use of closed loop control were found to be denser than their counterparts. This was found to be true also in case of manual reduction of power during each layer.
Improving Reliability for Linguistic Preference Relations Considering New Ordinal and Cardinal Consistency Measures
Authors: Wu Guolin , Wu Zhibin 
Published: February 2022

AbstractLinguistic preference relations (LPRs) and its variations served for different decision-making situations are significantly important instruments of qualitative decision-making. The consistency analysis of LPRs is a necessary prerequisite for further operations of these original preference relations so as to ensure that the final decision results are convincing. However, the existing consistency improvement methods for LPRs are difficult to guarantee the reliability of the revised LPRs. Because the suggested LPRs from these methods either not eliminate the ordinal inconsistency or not satisfy the expectation of minimum modification. In this paper, a new definition of ordinal consistency of LPRs is first proposed and then an optimization approach is constructed to eliminate ordinal inconsistency for LPRs. Secondly, a new cardinal consistency index for LPRs is proposed and a corresponding optimization model to increase the cardinal consistency level is presented. After that, an optimization model is proposed to simultaneously manage ordinal and cardinal inconsistency for LPRs. Last, the proposed models are applied to a real linguistic decision-making problem involving evaluation and selection of investment projects. The comparative analysis and discussion illustrate the applicability and effectiveness of the proposed models.
Particle radiotherapy and molecular therapies: mechanisms and strategies towards clinical applications
Authors: Helm Alexander , Fournier Claudia , Durante Marco 
Published: February 2022

Abstract
Immunotherapy and targeted therapy are now commonly used in clinical trials in combination with radiotherapy for several cancers. While results are promising and encouraging, the molecular mechanisms of the interaction between the drugs and radiation remain largely unknown. This is especially important when switching from conventional photon therapy to particle therapy using protons or heavier ions. Different dose deposition patterns and molecular radiobiology can in fact modify the interaction with drugs and their effectiveness. We will show here that whilst the main molecular players are the same after low and high linear energy transfer radiation exposure, significant differences are observed in post-exposure signalling pathways that may lead to different effects of the drugs. We will also emphasise that the problem of the timing between drug administration and radiation and the fractionation regime are critical issues that need to be addressed urgently to achieve optimal results in combined treatments with particle therapy.