bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inter-scanner brain MRI volumetric biases persist even in a harmonized multi-subject study of multiple sclerosis
Authors: Clark Kelly A. , O’Donnell Carly M. , Elliott Mark A. , Tauhid Shahamat , Dewey Blake E. , Chu Renxin , Khalil Samar , Nair Govind , Sati Pascal , DuVal Anna , Pellegrini Nicole , Bar-Or Amit , Markowitz Clyde , Schindler Matthew K. , Zurawski Jonathan , Calabresi Peter A. , Reich Daniel S. , Bakshi Rohit , Shinohara Russell T. ,   the NAIMS Cooperative
Published: May 2022

AbstractBackground/PurposeMulticenter study designs involving a variety of MRI scanners have become increasingly common. However, these present the issue of biases in image-based measures due to scanner or site differences. To assess these biases, we imaged 11 volunteers with multiple sclerosis (MS) with scan and rescan data at 4 sites.Materials and MethodsImages were acquired on Siemens or Philips scanners at 3-tesla. Automated white matter lesion detection and whole brain, gray and white matter, and thalamic volumetry were performed, as well as expert manual delineations of T1 and T2 (FLAIR) lesions. Random effect and permutation-based nonparametric modeling was performed to assess differences in estimated volumes within and across sites.ResultsRandom effect modeling demonstrated model assumption violations for most comparisons of interest. Non-parametric modeling indicated that site explained > 50% of the variation for most estimated volumes. This expanded to > 75% when data from both Siemens and Philips scanners were included. Permutation tests revealed significant differences between average inter- and intra-scanner differences in most estimated brain volumes (P < .05). The automatic activation of spine coil elements during some acquisitions resulted in a shading artifact in these images. Permutation tests revealed significant differences between thalamic volume measurements from acquisitions with and without this artifact.ConclusionDifferences in brain volumetry persisted across MR scanners despite protocol harmonization. These differences were not well explained by variance component modeling; however, statistical innovations for mitigating inter-scanner differences show promise in reducing biases in multi-center studies of MS.
Design and validation of the first family of photo-activatable ligands for melatonin receptors
Authors: Somalo-Barranco Gloria , Serra Carme , Lyons David , Piggins Hugh D. , Jockers Ralf , Llebaria Amadeu 
Published: May 2022

ABSTRACTMelatonin is a neurohormone released in a circadian manner with peak levels during the night. In mammals, melatonin mediates its effects mainly through G protein-coupled MT1 and MT2 receptors. Drugs acting on melatonin receptors are indicated for circadian rhythm- and sleep-related disorders and major depression. Pharmacological tools to study the activation of these receptors with high temporal resolution are lacking. Here, we synthesized a family of light-activatable caged melatonin compounds by covalently attaching o-nitrobenzyl (o-NB) or coumarin photocleavable groups to the N-position of melatonin. All caged compounds showed the expected decrease in binding affinity for MT1 and MT2. Among them, the o-NB derivative MCS-0382 showed the best uncaging and biological properties upon light activation with a significant increase (2.5 log left-shift) in affinity and potency in melatonin receptor binding and signaling, respectively. Generation of biologically active melatonin from MCS-0382 was further demonstrated by its ability to modulate the excitation of SCN neurons in rat brain slices. MCS-0382 is now available to study melatonin effects in a temporally controlled manner in cellular and physiological settings.
Spinal cord extracts of amyotrophic lateral sclerosis spread TDP-43 pathology in cerebral organoids
Authors: Tamaki Yoshitaka , Ross Jay P. , Alipour Paria , Catoire Hélène , Rochefort Daniel , Urushitani Makoto , Takahashi Ryosuke , Sonnen Joshua A. , Stifani Stefano , Dion Patrick A. , Rouleau Guy A. 
Published: May 2022

AbstractAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder caused by progressive loss of motor neurons and there is currently no effective therapy. Cytoplasmic mislocalization and aggregation of TAR DNA-binding protein 43 kDa (TDP-43) within the CNS is a pathological hallmark in sporadic ALS and prion-like propagation of pathogenic TDP-43 is thought to be implicated in disease progression. However, cell-to-cell transmission of pathogenic TDP-43 in the human CNS has not been confirmed experimentally.Here we used induced pluripotent stem cells (iPSCs)-derived cerebral organoids as recipient CNS tissue model that are anatomically relevant human brain. We injected postmortem spinal cord protein extracts individually from three non-ALS or five sporadic ALS patients containing pathogenic TDP-43 into the cerebral organoids to validate the templated propagation and spreading of TDP-43 pathology in human CNS tissue.We first demonstrated that the administration of spinal cord extracts from an ALS patient induced the formation of TDP-43 pathology that progressively spread in a time-dependent manner in cerebral organoids, suggesting that pathogenic TDP-43 from ALS functioned as seeds and propagated cell-to-cell to form de novo TDP-43 pathology. We also reported that the administration of ALS patient-derived protein extracts caused astrocyte proliferation to form astrogliosis in cerebral organoids, reproducing the pathological feature seen in ALS. Moreover, we showed pathogenic TDP-43 induced cellular apoptosis and that TDP-43 pathology correlated with genomic damage due to DNA double-strand breaks.Thus, our results provide evidence that patient-derived pathogenic TDP-43 can mimic the prion-like propagation of TDP-43 pathology in human CNS tissue. Our findings indicate that our assays with human cerebral organoids that replicate ALS pathophysiology have a promising strategy for creating readouts that could be used in future drug discovery efforts against ALS.
Next generation sequencing analysis of gastric cancer identifies the leukemia inhibitory factor receptor (LIFR) as a driving factor in gastric cancer progression and as a predictor of poor prognosis
Authors: Di Giorgio Cristina , Marchianò Silvia , Marino Elisabetta , Biagioli Michele , Roselli Rosalinda , Bordoni Martina , Bellini Rachele , Urbani Ginevra , Zampella Angela , Distrutti Eleonora , Donini Annibale , Graziosi Luigina , Fiorucci Stefano 
Published: May 2022

AbstractGastric cancer (GC) is the third cause of cancer-related-death worldwide. Nevertheless, because GC screening programs are not cost-effective, most patients receive diagnosis in the advanced stages, when surgical options are limited because the presence of diffuse disease. Peritoneal dissemination occurs in approximately one third of patients with GC and is a strong predictor of poor outcome. Despite the clinical relevance, biological and molecular mechanisms underlying the formation of peritoneal metastasis in GC remain poorly defined. To investigate this point, we conducted a high-throughput sequencing of transcriptome expression in paired samples of normal and neoplastic gastric mucosa in 31 GC patients with or without peritoneal carcinomatosis. The RNAseq analysis led to the discovery of a group of highly upregulated or downregulated genes that were differentially modulated in patients with peritoneal disease in comparison to GC patients without peritoneal involvement. Among these genes the leukemia inhibitory factor receptor (LIFR) and the one cut domain family member (ONECUT)2 were the only two genes that predicted survival at univariate statistical analysis. Because LIFR was the highest regulated gene we have further assessed whether this receptor plays a mechanistic role in GC dissemination. For this purpose, we have first assessed the expression of LIF, a member of IL-6 cytokine family, and LIFR in GC cell lines. Our results demonstrate that exposure of MKN45 cells to LIF, promoted a concentration-dependent proliferation and epithelial-mesenchymal transition (EMT) as shown by modulation of E-cadherin/vimentin gene expression along with JAK and STAT 3 phosphorylation and acquisition of a migratory phenotype. These features were reversed by in vitro treatment with a LIFR antagonist. Together, these data provide support to the notion that development of LIF/LIFR inhibitors might have a role in the treatment of GC.
Nitrogen palaeo-isoscapes: Changing spatial gradients of faunal δ15N in late Pleistocene and early Holocene Europe
Authors: Reade Hazel , Tripp Jennifer A. , Frémondeau Delphine , Sayle Kerry L. , Higham Thomas F.G. , Street Martin , Stevens Rhiannon E. 
Published: May 2022

AbstractNitrogen isotope (δ15N) analysis of animal tissue is widely used in archaeology and palaeoecology to investigate diet and ecological niche. Data interpretations require an understanding of nitrogen isotope compositions at the base of the food web (baseline δ15N). Significant variation in animal δ15N has been recognised at various spatiotemporal scales and linked to changes both in baseline δ15N and animal ecology. Isoscapes (models of isotope spatial variation) have proved a useful tool for investigating spatial variability in biogeochemical cycles in present-day marine and terrestrial ecosystems, but so far, their application to palaeo-data has been limited. Here, we present time-sliced nitrogen isoscapes for late Pleistocene and early Holocene Europe (c. 50,000 to 10,000 years BP) using herbivore collagen δ15N data. This period covers the Last Glacial-Interglacial Transition, during which significant variation in the terrestrial nitrogen cycle occurred. Our results show clear changes in spatial gradients of δ15N through time. Prediction of the lowest faunal δ15N values in northern latitudes after, rather than during, the Last Glacial Maximum is consistent with the Late Glacial Nitrogen Excursion (LGNE). We consider the potential of incorporating climatic covariate data into isoscape models but find their inclusion does not improve model performance. These findings have implications for investigating the drivers of the LGNE, which has been linked to increased landscape moisture and permafrost thaw, and for understanding changing isotopic baselines, which are fundamental for studies investigating diets, niche partitioning, and migration of higher trophic level animals.
Molecular insights into the effect of hexanediol on FUS phase separation
Authors: Zheng Tongyin , Wake Noah , Weng Shuo-Lin , Perdikari Theodora Myrto , Murthy Anastasia C. , Mittal Jeetain , Fawzi Nicolas L. 
Published: May 2022

Abstract1,6-hexanediol disrupts many phase-separated condensates in cells and in test tubes. In this study, we use a combination of microscopy, nuclear magnetic resonance (NMR) spectroscopy, molecular simulation, and biochemical assays to probe how alkanediols suppress phase separation and why certain isomers are more effective. Alkanediols of different lengths and configurations are all capable of disrupting phase separation of the RNA-binding protein Fused in Sarcoma (FUS), though potency varies depending on both geometry and hydrophobicity, which we measure directly. Alkanediols induce a shared pattern of changes to the protein chemical environment though to differing extents. Consistent with the view that alkanediols disrupt phase separation driven by hydrophobic groups, they decrease the thermal stability of a model globular protein. Conversely, 1,6-hexanediol does not disrupt charge-mediated phase separation, such as FUS RGG-RNA and poly-lysine/poly-aspartic acid condensates. All-atom simulations show that hydroxyl groups in alkanediols mediate interaction with protein backbone and polar amino acid side chains, while the aliphatic chain allows contact with hydrophobic and aromatic residues, providing a molecular picture of how amphiphilic interactions disrupt FUS phase separation.
Incorporating uniparental markers and demographic information in kinship analysis
Authors: Liu Jin-Xian , Li Meng-Yu 
Published: May 2022

AbstractKnowledge of kinship relations between members of wild populations is of great importance in ecological and conservation genetic studies. The bi-parentally inherited autosomal markers has been the Golden Standard in kinship analysis. However, analysis of kin relationship can be challenging in wild populations. The uni-parentally inherited markers and population demographic information can be helpful for identifying false-positive in kinship analysis. Here we showed how incorporating uniparental genetic and demographic information can improve the correct classification rate of kinship analyses by reanalyzing data of a recent study published in Science Advances. The application of next generation high-throughput sequencing to address fundamental ecological questions is of immense benefit to the field of molecular ecology, which could also generate uniparentally inherited organelle genomes together with nuclear data. We strongly recommended that uniparental genetic markers and demographic information be seriously considered in kinship analyses of wild populations.
Skull and scalp segmentation in neonatal cerebral MRI using subject-specific probability models
Authors: Hokmabadi Elham , Abrishami Moghaddam Hamid , Mohtasebi Mehrana , Kazemloo Amirreza , Gity Masume , Wallois Fabrice 
Published: May 2022

AbstractThis study presents a new approach for segmenting cranial bones in magnetic resonance images (MRIs) acquired from neonates in the gestational age range of 39 to 42 weeks. the approach uses subject-specific probability maps of the skull and scalp, created from atlas computed tomography (CT) images taken retrospectively from neonates in the same age range. the method also uses a subject-specific probability map of cerebrospinal fluid (CSF), constructed from retrospective atlas MRIs. To build skull, scalp, and CSF probability maps, a subject-specific bimodal MR-CT neonatal head template is employed. In the next step, the subject-specific probability maps are fed to the expectation maximization algorithm in conjunction with Markov random field method implemented in FSL software to segment the skull and scalp from the input MR image. The results of the proposed method were evaluated through various experiments. First, we employed our method as a brain tissue extractor and compared its results with public methods such as the Brain Extraction Tool (BET) and Brain Surface Extractor (BSE). Second, we calculated the similarity in shape between the frontal and occipital sutures (which had been reconstructed from segmented cranial bones) and the ground truth. For this purpose, modified versions of the Dice similarity coefficient (DSC) were adopted and used. Finally, retrospective data including MRI and CT images obtained from the same neonate within a short time interval were used. After aligning the two images, the DSC and modified Hausdorff distance (MHD) were used to compare the similarity of the cranial bones in the MR and CT images. Furthermore, the anterior fontanel size was compared to the normal size reported for neonates in the same age range. Cranial bone thickness was calculated and compared to normal values reported for healthy neonates. The results of these experiments demonstrated the success of our segmentation method. The algorithm for creating subject-specific atlases is publicly accessible through a graphical user interface atmedvispy.ee.kntu.ac.ir.
Modelling the within-host spread of SARS-CoV-2 infection, and the subsequent immune response, using a hybrid, multiscale, individual-based model. Part I: Macrophages
Authors: Rowlatt C. F. , Chaplain M. A. J. , Hughes D. J. , Gillespie S. H. , Dockrell D. H. , Johannessen I. , Bowness R. 
Published: May 2022

AbstractIndividual responses to SARS-CoV-2 infection vary significantly, ranging from mild courses of infection that do not require hospitalisation to the development of disease which not only requires hospitalisation but can be fatal. Whilst many immunological studies have revealed fundamental insights into SARS-CoV-2 infection and COVID-19, mathematical and computational modelling can offer an additional perspective and enhance understanding. The majority of mathematical models for the within-host spread of SARS-CoV-2 infection are ordinary differential equations, which neglect spatial variation. In this article, we present a hybrid, multiscale, individual-based model to study the within-host spread of SARS-CoV-2 infection. The model incorporates epithelial cells (each containing a dynamical model for viral entry and replication), macrophages and a subset of cytokines. We investigate the role of increasing initial viral deposition, increasing delay in type I interferon secretion from epithelial cells (as well as the magnitude of secretion), increasing macrophage virus internalisation rate and macrophage activation, on the spread of infection.
A new device for continuous non-invasive measurements of leaf water content using NIR-transmission allowing dynamic tracking of water budgets
Authors: Kaiser Hartmut 
Published: May 2022

AbstractLeaf water content (LWC) permanently fluctuates under variable transpiration rate and sap flow and influences e.g. stomatal responses and osmotic adjustment of plant cells. Continuous recordings of LWC are therefore central for the investigation of the regulatory networks stabilizing leaf hydration. Available measurement methods, however, either influence local hydration, interfere with the local leaf micro-environment or cannot easily be combined with other techniques. To overcome these limitations a non-invasive sensor was developed which uses light transmission in the NIR range for precise continuous recordings of LWC. For LWC measurements the transmission ratio of two NIR wavelengths was recorded using a leaf-specific calibration. Pulsed measurement beams enabled measurements under ambient light conditions. The contact-free sensor allows miniaturization and can be integrated into many different experimental settings. Example measurements of LWC during disturbances and recoveries of leaf water balance show the high precision and temporal resolution of the LWC sensor and demonstrate possible method combinations. Simultaneous measurements of LWC and transpiration allows to calculate petiole influx informing about the dynamic leaf water balance. With simultaneous measurements of stomatal apertures the relevant stomatal and hydraulic processes are covered, allowing insights into dynamic properties of the involved positive and negative feed-back loops.
Realizing employee and organizational performance gains through electronic human resource management use in developing countries
Authors: Nyathi Musa , Kekwaletswe Ray 
Published: May 2022

PurposeThe purpose of this paper is to propose and test a model designed to realize employee and organizational performance gains in developing economies.Design/methodology/approachData were collected through a survey involving 35 organizations using electronic human resource management (e-HRM) systems. A purposive sampling technique was employed. Regression analysis making use of Process macro in Statistical Package for the Social Sciences (SPSS) was used to analyze the data.FindingsDespite its infancy in African countries, e-HRM use has a positive effect on employee and organizational performance. The organization-wide gains are enhanced through employee performance mediation.Practical implicationsElectronic-HRM use, complemented by human resource best practices that impact positively on individual performance, is likely to enhance organizational performance gains. Employee performance mediation effect is likely to further enhance the effect of e-HRM usage on organizational performance.Originality/valueThis study represents a first attempt to examine the role of employee performance as an intervening variable in the relationship between e-HRM use and organizational performance. The findings bring into attention the role of organizational members' performance in explaining organizational performance gains. The findings also result in a model that should lead to increased employee and organizational performance.
The effect of succession on corporate governance reform under the Chinese clan culture context
Authors: Wang Linchuan , Gao Qianying , Wu Cisheng 
Published: May 2022

PurposeThe fundamental component of Confucian culture is clan culture, which stresses that family ties are the most important of all social relationships and have an essential impact on the governance model of family firms in Southeast Asian countries, especially in China. This study investigates complex relationships among family firm succession and corporate governance reform in the context of Chinese clan culture.Design/methodology/approachDrawing upon the analysis of altruistic behavior and conflict in succession process in family firm, the study uses a moderation model to capture the relationships between succession and governance reform in the context of clan culture. This study conducts an empirical study on 295 Chinese listed family firms that initiated intergenerational succession from 2008 to 2018 to test the model.FindingsThe empirical results suggest that the different stages of the succession will positively affect the family firm's governance reform, whether it is the stage in which the successor takes over the firm or the stage in which the successor completely controls the firm. Furthermore, the succession-governance reform relationship is negatively moderated by the clan concept of the actual controller.Originality/valueThis paper fulfills an identified need to study how succession in the family firm can accelerate corporate governance reform (transition from relation-based governance to rule-based governance). The research results provide evidence from the firm-level under the Chinese clan culture context to understand the complex relationship between succession and corporate governance.
Single versus multiple salesforce go-to-market strategy: the impact of sales orientation on conflict, salesperson-owned loyalty and buyer-exit propensity
Authors: Anaza Nwamaka A. , Rutherford Brian N. , Wu Gavin Jiayun , Bhattarai Ashok 
Published: May 2022

Purpose
Drawing on the organizational buying decision-making framework, the purpose of this study is to investigate how sales orientation (SOCO) affects buyers’ conflict, salesperson-owned loyalty and buyers’ propensity to end a supply relationship when selling firms use a single versus multiple salesforce go-to-market strategy.

Design/methodology/approach
Survey data was analyzed with a sample of organizational buyers. Confirmatory factor analysis and structural equation modeling were used to analyze the data.

Findings
Findings reveal that a selling firm’s go-to-market salesforce strategy moderates certain relational aspects of the buyer–salesperson relationship, consequently influencing a buyer’s decision to end a supply relationship.

Research limitations/implications
Empirically, these findings indicate that the effects of selling orientation on conflict, salesperson-owned loyalty and exit intentions are not only based on the salesperson’s efforts but are conditional on the selling firm’s go-to-market strategy, particularly with the implementation of multiple salespeople selling to a particular industrial buyer.

Practical implications
These results suggest that a salesforce go-to-market strategy conveys serious consequences on buying decisions. Given that a go-to-market strategy involving multiple salespeople impacts the buyer’s relationship with the selling firm to a greater degree, managerial oversight must remain present when selling firms decide to pursue such a go-to-market strategy.

Originality/value
The empirical investigation of a salesforce go-to-market strategy is an original pursuit. Specifically, this study shows that while it is critical that buying and selling firms monitor buyer–salesperson relationships as the basis for supply partnerships, these exchanges are largely contingent on the selling firm’s go-to-market strategy.