bluuebunny/crossref_metadata_2025_split huggingface dataset:
Beyond body maps: information content of specific body parts is distributed across the somatosensory Homunculus
Authors: Muret Dollyane , Root Victoria , Kieliba Paulina , Clode Danielle , Makin Tamar R. 
Published: August 2021

AbstractThe somatosensory homunculus in primary somatosensory cortex (S1) is topographically organised, with relatively high selectivity to each body part in its primary area. This dominant feature may eclipse other organising principles in S1. Recent multivariate methodologies allow us to identify representational features beyond selectivity, e.g., information content, providing new opportunities to characterise the homunculus. Using Representational Similarity Analysis, we asked whether body part information content can be identified in S1 beyond the primary area of a given body part. Representational dissimilarities in fMRI activity patterns were compared between different body parts (face, hand and feet) and subparts (e.g., fingers), and between different actions performed with the same body part. Throughout the S1 homunculus, we identified significant dissimilarities between non-primary body parts (e.g., between the hand and the lips in the foot area). We also observed significant dissimilarities between body subparts in distant non-primary areas (e.g., different face parts in the foot area). Finally, we could significantly dissociate between two movements performed by one body part (e.g., the hand) well beyond its primary area (e.g., in the foot and face areas), even when focusing the analysis along the most topographically organised sub-region of S1, Brodmann area 3b. Altogether, our results demonstrate that body part and action-related information content is more distributed across S1 homunculus than previously considered. While this finding does not revoke the general topographic organising principle of S1, it reveals yet unexplored underlying information contents that could be harnessed for rehabilitation, as well as novel brain-machine interfaces.
SARS-CoV-2 infection induces soluble platelet activation markers and PAI-1 in the early moderate stage of COVID-19
Authors: Al-Tamimi Abaher O. , Yusuf Ayesha M. , Jayakumar Manju N. , Ansari Abdul W. , Elhassan Mona , AbdulKarim Fatema , Kannan Meganathan , Halwani Rabih , Ahmad Firdos 
Published: August 2021

AbstractIntroductionCoagulation dysfunction and thromboembolism emerge as strong comorbidity factors in severe COVID-19. However, it is unclear when particularly platelet activation markers and coagulation factors dysregulated during the pathogenesis of COVID-19. Here, we sought to assess the levels of coagulation and platelet activation markers at moderate and severe stages of COVID-19 to understand the pathogenesis.MethodsTo understand this, hospitalized COVID-19 patients with (severe cases that required intensive care) or without pneumonia (moderate cases) were recruited. Phenotypic and molecular characterizations were performed employing basic coagulation tests including PT, APTT, D-Dimer and TFPI. The flow cytometry-based multiplex assays were performed to assess FXI, anti-thrombin, prothrombin, fibrinogen, FXIII, P-selectin, sCD40L, plasminogen, tissue-plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) and D-Dimer.ResultsThe investigations revealed induction of plasma P-selectin and CD40 ligand (sCD40L) in moderate COVID-19 cases which were significantly abolished with the progression of COVID-19 severity. Moreover, a profound reduction in plasma tissue factor pathway inhibitor (TFPI) and FXIII were identified particularly in the severe COVID-19. Further analysis revealed fibrinogen induction in both moderate and severe patients. Interestingly, an elevated PAI-1 more prominently in moderate, and tPA particularly in severe COVID-19 cases were observed. Particularly, the levels of fibrinogen and tPA directly correlated with the severity of the disease.ConclusionsIn summary, induction of soluble P-selectin, sCD40L, fibrinogen and PAI-1 in moderate COVID-19 cases suggests the activation of platelets and coagulation system before patients require intensive care. These findings would help in designing better thromboprophylaxis to limit the COVID-19 severity.
Counterbalance of Foxp3 and IDO expression at different tumor stages in aggressive breast cancer subtypes
Authors: Canzoneri Romina , Lacunza Ezequiel , Rabassa Martín E. , Cavalli Fiorella A. , Ferretti Valeria , Barbera Luis A. , Cretón Aldo , Croce Maria Virginia , Larrain Marina T. Isla 
Published: August 2021

ABSTRACTFoxp3 and IDO1 are known immunomodulatory molecules involved in tumor escape and could be related to tumor infiltrating lymphocytes (TILs) in the tumor microenvironment. In this study, tumoral Foxp3 and IDO1 expression in breast cancer were evaluated in relation to lymphocyte biomarkers such as CD8 and CD45R0, regulatory T cells, as well as intratumoral and stromal TILs (iTILs and sTILs, respectively). Clinical and histopathological features were also included in the analysis. Foxp3 and IDO1 were found in tumor cells showing mainly cytoplasmic patterns in 60% and 62% tumor samples, respectively. TILs were found in 76% of samples; iTILs were detected in 92% of those samples and sTILs in 55%. Foxp3+ TILs were detected only in 12% of TILs+ samples associated with tumoral Foxp3 expression. Tumoral Foxp3 was mainly expressed at lower tumor stages while IDO1 expression was associated with advanced tumor stages; both correlated with CD8+ TILs which were observed in 77% of TILs+ samples. CD45R0+ were observed in 81% of TILs+ samples and correlated with higher tumor stages and poorly differentiated tumors. In ER negative tumors, an inverse correlation between Foxp3 and IDO1 tumoral expression was found in relation to tumor stage. TNBC subtype showed a positive correlation with the presence of iTILs. In silico analysis showed that Foxp3 and coexpressed genes in breast cancer were associated with immune response genes. Foxp3 was found predominantly in Basal and Her2-enriched subtypes in relation to Luminal A subtype, by RNA seq and RNA microarray database analysis. In conclusion, the expression of Foxp3 and IDO1 in tumors at different stages suggests a potential compensatory mechanism to evade the strong CTL response observed. This is relevant since the cumulative data indicates that Foxp3 as well as IDO1 could be potential targets of immunotherapy in patients with tumors at different stages and for the most aggressive breast cancer subtypes such as TNBC and Her2-enriched.HIGHLIGHTSFoxp3 and IDO1 were found overexpressed in the cytoplasm of tumor cells, observed in BC samples at early or advanced tumor stages, respectively, both associated with abundant cytotoxic CD8+ lymphocytes infiltrates.Tumor immunosuppression by Foxp3 and IDO1 tumoral expression could counteract the attempt of the host’s immune system to eradicate the tumor by CD8+ and CD45R0+ TILs cytotoxic activity.It is well-known the tolerogenic role of Foxp3 in Treg and less understood the role of Foxp3 in tumors. However, there is increasing evidence that Foxp3+ tumor cells appear to promote an immunosuppressive microenvironment similar to Treg. Whether this is a consequence of the effect of other immunosuppressive factors secreted by the tumor cells which can be induced by Foxp3 expression, such as TGFβ, remains to be determined.
Rates of convergence in the two-island and isolation-with-migration models
Authors: Legried Brandon , Terhorst Jonathan 
Published: August 2021

AbstractA number of powerful demographic inference methods have been developed in recent years, with the goal of fitting rich evolutionary models to genetic data obtained from many populations. In this paper we investigate the statistical performance of these methods in the specific case where there is continuous migration between populations. Compared with earlier work, migration significantly complicates the theoretical analysis and demands new techniques. We employ the theories of phase-type distributions and concentration of measure in order to study the two-island and isolation-with-migration models, resulting in both upper and lower bounds. For the upper bounds, we consider inferring rates of coalescent and migration on the basis of directly observing pairwise coalescent times, and, more realistically, when (conditionally) Poisson-distributed mutations dropped on latent trees are observed. We complement these upper bounds with information-theoretic lower bounds which establish a limit, in terms of sample size, below which inference is effectively impossible.
Time Evolution of the Stroke Symptom-Herb Networks Based on TCM Prescriptions
Authors: Fu Xing , Li Qianqian , Yang Feng , Zhou Ranran , Li Ran , Hou Jianchen , Tao Xiaohua 
Published: August 2021

AbstractTraditional Chinese Medicine (TCM) has its origins in distant antiquity and has piled up over a long time with much knowledge about diseases, especially stroke. Different combinations of symptom variables yield different combinations of herbs to form a myriad of prescriptions, and they have undergone repeated confirmation and are worthy objects of excavation and analysis. Herbal studies on stroke have developed from genomics to transcriptomics, proteomics and metabolomics, yet more thought is needed on putting time in a wider perspective of the symptoms and herbs for stroke in Chinese medicine.Due to this, we studied the dynamic structure of TCM prescriptions on stroke, using over 270 TCM prescription books containing 2231 prescriptions related to stroke recorded from 341 to 2000 CE. We labeled the functions of the prescriptions with the symptoms based on subject terms in MESHNeurologic Manifestations, then standardized the herbs in the prescriptions, and finally connected the co-occurring symptoms and herbs in the prescriptions to build an undirected complex network. The Stroke Symptom-Herb Networks (SSHNs) can be seen from its network characteristics that it is not a random network and has small-world characteristics. It has experienced two peaks in its nearly 1700-year history, during the Song dynasty, the Ming and Qing dynasties. From 600 years onwards, the core herb cluster has been initially formed. The comparison of sub-network similarities allowed us to identify several symptoms with similar herb clusters.We divided the community based on modularity, and by analyzing the community evolution, we found a more fixed historical evolutionary trend withHemiplegiaandSialorrheanodes and their associated symptom and herb nodes. In the time series analysis, we found many symptom-herb combinations that were consistently closely related to historic time depends on assessing the similarity between the symptoms and the herbs. The complex network provides a distinctive perspective for understanding the symptom-herb relationships embedded in TCM prescriptions in remote antiquity.
Directed Differentiation of Human Pluripotent Stem Cells into Radial Glia and Astrocytes Bypasses Neurogenesis
Authors: Jovanovic Vukasin M. , Malley Claire , Tristan Carlos A. , Ryu Seungmi , Chu Pei-Hsuan , Barnaeva Elena , Ormanoglu Pinar , Mercado Jennifer Colon , Michael Sam , Ward Michael E. , Simeonov Anton , Singeç Ilyas 
Published: August 2021

AbstractDerivation of astrocytes from human pluripotent stem cells (hPSCs) is inefficient and cumbersome, impeding their use in biomedical research. Here, we developed a highly efficient chemically defined astrocyte differentiation strategy that overcomes current limitations. This approach largely bypasses neurogenesis, which otherwise precedes astrogliogenesis during brain development and in vitro experiments. hPSCs were first differentiated into radial glial cells (RGCs) exhibiting in vivo-like radial glia signatures. Activation of NOTCH and JAK/STAT pathways in bona fide RGCs resulted in direct astrogliogenesis confirmed by expression of various glial markers (NFIA, NFIB, SOX9, CD44, S100B, GFAP). Transcriptomic and genome-wide epigenetic analyses confirmed RGC-to-astrocyte differentiation and absence of neurogenesis. The morphological and functional identity of hPSC-derived astrocytes was confirmed by using an array of methods (e.g. electron microscopy, calcium imaging, co-culture with neurons, grafting into mouse brains). Lastly, the scalable protocol was adapted to a robotic platform and used to model Alexander disease. In conclusion, our findings uncover remarkable plasticity in neural lineage progression that can be exploited to manufacture large numbers of human hPSC-derived astrocytes for drug development and regenerative medicine.
Profiling Transcription Initiation in Peripheral Leukocytes Reveals Severity-Associated Cis-Regulatory Elements in Critical COVID-19
Authors: Lam Michael Tun Yin , Duttke Sascha H. , Odish Mazen F. , Le Hiep D. , Hansen Emily A. , Nguyen Celina T. , Trescott Samantha , Kim Roy , Deota Shaunak , Chang Max W. , Patel Arjun , Hepokoski Mark , Alotaibi Mona , Rolfsen Mark , Perofsky Katherine , Warden Anna S. , Foley Jennifer , Ramirez Sydney I , Dan Jennifer M. , Abbott Robert K , Crotty Shane , Crotty Alexander Laura E , Malhotra Atul , Panda Satchidananda , Benner Christopher W. , Coufal Nicole G. 
Published: August 2021

AbstractThe contribution of transcription factors (TFs) and gene regulatory programs in the immune response to COVID-19 and their relationship to disease outcome is not fully understood. Analysis of genome-wide changes in transcription at both promoter-proximal and distal cis-regulatory DNA elements, collectively termed the ’active cistrome,’ offers an unbiased assessment of TF activity identifying key pathways regulated in homeostasis or disease. Here, we profiled the active cistrome from peripheral leukocytes of critically ill COVID-19 patients to identify major regulatory programs and their dynamics during SARS-CoV-2 associated acute respiratory distress syndrome (ARDS). We identified TF motifs that track the severity of COVID- 19 lung injury, disease resolution, and outcome. We used unbiased clustering to reveal distinct cistrome subsets delineating the regulation of pathways, cell types, and the combinatorial activity of TFs. We found critical roles for regulatory networks driven by stimulus and lineage determining TFs, showing that STAT and E2F/MYB regulatory programs targeting myeloid cells are activated in patients with poor disease outcomes and associated with single nucleotide genetic variants implicated in COVID-19 susceptibility. Integration with single-cell RNA-seq found that STAT and E2F/MYB activation converged in specific neutrophils subset found in patients with severe disease. Collectively we demonstrate that cistrome analysis facilitates insight into disease mechanisms and provides an unbiased approach to evaluate global changes in transcription factor activity and stratify patient disease severity.
Suppressor of Fused regulation of Hedgehog Signaling is Required for Proper Astrocyte Differentiation
Authors: Spice Danielle M. , Dierolf Joshua , Kelly Gregory M. 
Published: August 2021

AbstractHedgehog signaling is essential for vertebrate development, however, less is known about the negative regulators that influence this pathway. Using the mouse P19 embryonal carcinoma cell model, Suppressor of Fused (SUFU), a negative regulator of the Hedgehog pathway, was investigated during retinoic acid-induced neural differentiation. We found Hedgehog signaling was activated in the early phase of differentiation but was inactive during terminal differentiation of neurons and astrocytes. Early activation was required for neural differentiation however, it alone was not sufficient to induce neural lineages. SUFU, which regulates signaling at the level of GLI, remained relatively unchanged during differentiation, but its loss through CRISPR-Cas9 gene editing resulted in ectopic expression of Hedgehog target genes. Interestingly, these SUFU-deficient cells were unable to differentiate without retinoic acid, and when used they showed delayed and decreased astrocyte differentiation; neuron differentiation was unaffected. Ectopic activation of Hh target genes in SUFU-deficient cells remained throughout retinoic acid-induced differentiation and this was accompanied by the loss of GLI3, despite the presence of the Gli3 message. Thus, the study indicates the proper timing and proportion of astrocyte differentiation requires SUFU, and its normal regulation of GLI3 to maintain Hh signaling in an inactive state.
The effects of overconfident yield forecasting on cross-coverage level crop insurance demand
Authors: Michaud Clayton P. 
Published: August 2021

PurposeThis paper examines the effect of overconfident yield forecasting (optimism bias) on crop insurance coverage level choices across both yield and revenue insurance.Design/methodology/approachThis study simulates a representative producer’s preferred coverage level for both yield and revenue insurance under three potential models of decision-making and four potential manifestations of overconfident yield forecasting. The study then uses this framework to examine how coverage level choices change as overconfidence increases (decreases).FindingsAs overconfidence increases, producers prefer lower levels of crop insurance coverage than they would otherwise prefer, with extreme overconfidence inducing farmers to buy no insurance at all. While overconfidence affects cross-coverage demand for revenue and yield insurance similarly, this effect is more pronounced for yield insurance. Cross-coverage level demand for revenue insurance is relatively stable across changes in the correlation between prices and yields.Practical implicationsThis research has important implications for crop insurance subsidy design and crop insurance demand modeling.Originality/valueThere is a growing body of literature suggesting that producers are overconfident with regard to their future yield risk and that this bias reduces their willingness to pay for risk management tools such as crop insurance. This is the first study to look at how such overconfidence affects cross-coverage level demand for crop insurance.
From rationale to lessons learned in the cloud information security risk assessment: a study of organizations in Sweden
Authors: Faizi Ana , Padyab Ali , Naess Andreas 
Published: August 2021

Purpose
This study aims to address the issue of practicing information security risk assessment (ISRA) on cloud solutions by studying municipalities and large organizations in Sweden.

Design/methodology/approach
Four large organizations and five municipalities that use cloud services and conduct ISRA to adhere to their information security risk management practices were studied. Data were gathered qualitatively to answer the study’s research question: How is ISRA practiced on the cloud? The Coat Hanger model was used as a theoretical lens to study and theorize the practices.

Findings
The results showed that the organizations aimed to follow the guidelines, in the form of frameworks or their own experience, to conduct ISRA; furthermore, the frameworks were altered to fit the organizations’ needs. The results further indicated that one of the main concerns with the cloud ISRA was the absence of a culture that integrates risk management. Finally, the findings also stressed the importance of a good understanding and a well-written legal contract between the cloud providers and the organizations using the cloud services.

Originality/value
As opposed to the previous research, which was more inclined to try out and evaluate various cloud ISRA, the study provides insights into the practice of cloud ISRA experienced by the organizations. This study represents the first attempt to investigate cloud ISRA that organizations practice in managing their information security.
Comparative analysis of three categories of four-DOFs exoskeleton mechanism based on relative movement offsets
Authors: Cao Qiang , Li Jianfeng , Dong Mingjie 
Published: August 2021

Purpose
The purpose of this paper is to evaluate three categories of four-degrees of freedom (4-DOFs) upper limb rehabilitation exoskeleton mechanisms from the perspective of relative movement offsets between the upper limb and the exoskeleton, so as to provide reference for the selection of exoskeleton mechanism configurations.

Design/methodology/approach
According to the configuration synthesis and optimum principles of 4-DOFs upper limb exoskeleton mechanisms, three categories of exoskeletons compatible with upper limb were proposed. From the perspective of human exoskeleton closed chain, through reasonable decomposition and kinematic characteristics analysis of passive connective joints, the kinematic equations of three categories exoskeletons were established and inverse position solution method were addressed. Subsequently, three indexes, which can represent the relative movement offsets of human–exoskeleton were defined.

Findings
Based on the presented position solution and evaluation indexes, the joint displacements and relative movement offsets of the three exoskeletons during eating movement were compared, on which the kinematic characteristics were investigated. The results indicated that the second category of exoskeleton was more suitable for upper limb rehabilitation than the other two categories.

Originality/value
This paper has a certain reference value for the selection of the 4-DOFs upper extremity rehabilitation exoskeleton mechanism configurations. The selected exoskeleton can ensure the safety and comfort of stroke patients with upper limb dyskinesia during rehabilitation training.
The Giotto's Bell Tower at Firenze (Italy): foundation assessment
Authors: Coli Massimo , Tanganelli Marco , Baldi Michele , Viti Stefania 
Published: August 2021

PurposeThe paper is aimed at assessing the safety of the Giotto's Bell Tower, with special attention to its foundation system, i.e. the foundation works and soil. The tower, well known all over the world, has a squared plan, with sides of 14.45 m each, and a total height equal to 84.7 m. The structural response of the tower is assessed with reference to the gravitational load and to the expected seismic action, quantified according to the seismic hazard of the site and the foundation soil.Design/methodology/approachA simplified analysis has been performed to check the safety level of the tower to seismic actions. Special attention has been paid to quantify the horizontal actions representing the seismic loads. Such quantification, indeed, has been made both through the elastic spectrum of the tower and by performing a site response analysis on the foundation soil, represented as a one-dimensional stratification of soil layers, described on the basis of experimental investigations. After defining the loading actions, a simplified assessment of the foundation safety has been made by considering the action over foundation, the geotechnical data and the safety factor.FindingsThe findings of the paper concern the assessment of the safety of the tower's foundation system. A lot of experimental data on the foundation soil, provided by various geological investigations, have been provided and used for the assessment. Moreover, the mechanical properties of the materials used for the structure have been collected and shown in the paper.Originality/valueThe paper collects a lot of technical information regarding the Giotto's Bell Tower, both regarding its foundation soil and the constituting materials. On the basis of the collected information, a structural analysis has been made to assess the seismic safety of the tower, and the results of such assessment are provided and discussed.