bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of autonomic nervous system dysfunction in complex regional pain syndrome
Authors: Lee Ho-Jin , Lee Kang Hee , Moon Jee Youn , Kim Yong-Chul 
Published: January 2021

Background
We aimed to investigate the prevalence of dysautonomia in complex regional pain syndrome (CRPS) via the combined autonomic nervous system (ANS) function tests, including the deep breathing test (DBT), orthostatic test (OST) and sympathetic skin response (SSR).

Method
We retrospectively examined 263 patients who underwent the combined ANS tests to evaluate CRPS between August 2013 and December 2016. Based on the Budapest clinical criteria, patients were stratified into confirmed-CRPS or suspected-CRPS groups. We performed binary logistic regression analysis using the inverse probability of treatment weighting to investigate the association between the tests and CRPS. Sensitivity and specificity were calculated to assess the diagnostic performance of the ANS tests for CRPS. We compared the results of these tests between the outcomes of sympathetic nerve blocks (SNBs).

Results
Among 247 patients, finally included in this study, 199 patients (80.6%) were diagnosed with CRPS. Abnormal results of overall or each ANS function test showed significant associations with CRPS, excluding OST (overall abnormality: OR 2.44, 95% CI 1.51 to 3.95; p<0.001; DBT: OR 2.57, 95% CI 1.23 to 5.38, p=0.013; OST: OR 1.88, 95% CI 0.92 to 3.84, p=0.085; SSR: OR 2.71, 95% CI 1.38 to 5.32, p=0.004). However, their prevalence in CRPS and their sensitivities for CRPS were low (overall abnormality: 26.1%; each test: <15%). No significant association existed between dysautonomia and SNB outcomes.

Conclusion
Dysautonomia, as evaluated using the combined ANS tests, were observed in a small portion of patients with CRPS. The diagnostic performances of these tests for CRPS were inadequate for clinical purposes.
Note on Tsallis holographic dark energy in Brans–Dicke cosmology
Authors: Yadav Anil Kumar 
Published: January 2021

AbstractIn this paper, we have investigated that the power law variation of Brans–Dicke scalar field $$(\phi )$$

(
ϕ
)

with scale factor (a) is not validated by field equations in general for the Universe filled with dark matter and Tsallis type holographic dark energy. However, for specific choice of free parameters $$(\omega = -\frac{3}{2}$$

(
ω
=
-

3
2

and $$n = -1)$$

n
=
-
1
)

which are differ from its values fixed in Ghaffari et al. (Eur Phys J C 78:706, 2018) to describe various physical properties of the Universe in derived model, the power law variation of $$\phi $$
ϕ
with a leads to consistent results. Further, we notice that the energy conservation law for Tsallis holographic dark energy in Brans–Dicke gravity does not hold.
Stratigraphic and sedimentological aspects of the worldwide distribution of
Apectodinium
in Paleocene/Eocene Thermal Maximum deposits
Authors: Denison Christopher N. 
Published: January 2021

Abstract

The Paleocene/Eocene Thermal Maximum (PETM) is characterized by pronounced global warming and associated environmental changes. In the more-or-less two decades since prior regional syntheses of
Apectodinium
distribution at the PETM, extensive biological and geochemical datasets have elucidated the effect of rising world temperatures on climate and the biome. A Carbon Isotope Excursion (CIE) that marks the Paleocene/Eocene Boundary is associated with an acme of marine dinocysts of the genus
Apectodinium
in many locations. Distinctive foraminiferal and calcareous nannofossil populations may also be present.

For this updated, dinocyst-oriented view of the PETM, data from worldwide locations have been evaluated with an emphasis on stratigraphic and sedimentological context. What has emerged is that a change in lithology is common, often to a distinctive siltstone or claystone unit, which contrasts with underlying and overlying lithotypes. This change, present in shallow marine/coastal settings and in deep-water turbidite deposits, is attributed to radical modifications of precipitation and erosional processes. An abrupt boundary carries the implication that some time (of unknowable duration) is potentially missing, which then requires caution in the interpretation of the pacing of events in relation to that boundary. In most instances an ‘abrupt’ or ‘rapid’ CIE onset can be attributed to a data gap at a hiatus, particularly in shallow shelf settings where transgression resulted from sea-level rise associated with the PETM. Truly gradational lower boundaries of the PETM interval are quite unusual and, if present, are poorly known so far. Gradational upper boundaries are more common, but erosional upper boundaries have been reported.

Taxonomic changes have been made to clarify identification issues that have adversely impacted some biostratigraphic interpretations.
Apectodinium hyperacanthum
has been retained in
Wetzeliella
, its original genus. The majority of specimens previously assigned to
Apectodinium hyperacanthum
or
Wetzeliella
(
Apectodinium
)
hyperacanthum
have been reassigned to an informal species,
Apectodinium
sp. 1.
Dracodinium astra
has been retained in its original genus as
Wetzeliella astra
and is emended.
Tumor Mutational Burden Is Polygenic and Genetically Associated with Complex Traits and Diseases
Authors: Sun Xiwei , Xue Angli , Qi Ting , Chen Dan , Shi Dandan , Wu Yang , Zheng Zhili , Zeng Jian , Yang Jian 
Published: January 2021

Abstract

Tumor mutational burden (TMB) is an emerging biomarker of response to immunotherapy in solid tumors. However, the extent to which variation in TMB between patients is attributable to germline genetic variation remains elusive. Here, using 7,004 unrelated patients of European descent across 33 cancer types from The Cancer Genome Atlas, we show that pan-cancer TMB is polygenic with approximately 13% of its variation explained by approximately 1.1 million common variants altogether. We identify germline variants that affect TMB in stomach adenocarcinoma through altering the expression levels of BAG5 and KLC1. Further analyses provide evidence that TMB is genetically associated with complex traits and diseases, such as smoking, rheumatoid arthritis, height, and cancers, and some of the associations are likely causal. Overall, these results provide new insights into the genetic basis of somatic mutations in tumors and may inform future efforts to use genetic variants to stratify patients for immunotherapy.

Significance:
This study provides evidence for a polygenic architecture of tumor mutational burden and opens an avenue for the use of whole-genome germline genetic variations to stratify patients with cancer for immunotherapy.
Interventional Radiology for Local Immunotherapy in Oncology
Authors: Tselikas Lambros , Champiat Stephane , Sheth Rahul A. , Yevich Steve , Ammari Samy , Deschamps Frederic , Farhane Siham , Roux Charles , Susini Sandrine , Mouraud Severine , Delpla Alexandre , Raoult Thibault , Robert Caroline , Massard Christophe , Barlesi Fabrice , Soria Jean-Charles , Marabelle Aurélien , de Baere Thierry 
Published: January 2021

Abstract
Human intratumoral immunotherapy (HIT-IT) is under rapid development, with promising preliminary results and high expectations for current phase III trials. While outcomes remain paramount for patients and the referring oncologists, the technical aspects of drug injection are critical to the interventional radiologist to ensure optimal and reproducible outcomes. The technical considerations for HIT-IT affect the safety, efficacy, and further development of this treatment option. Image-guided access to the tumor allows the therapeutic index of a treatment to be enhanced by increasing the intratumoral drug concentration while minimizing its systemic exposure and associated on-target off-tumor adverse events. Direct access to the tumor also enables the acquisition of cancer tissue for sequential sampling to better understand the pharmacodynamics of the injected immunotherapy and its efficacy through correlation of immune responses, pathologic responses, and imaging tumor response. The aim of this article is to share the technical insights of HIT-IT, with particular consideration for patient selection, lesion assessment, image guidance, and technical injection options. In addition, the organization of a standard patient workflow is discussed, so as to optimize HIT-IT outcome and the patient experience.
Network for Biomarker Immunoprofiling for Cancer Immunotherapy: Cancer Immune Monitoring and Analysis Centers and Cancer Immunologic Data Commons (CIMAC-CIDC)
Authors: Chen Helen X. , Song Minkyung , Maecker Holden T. , Gnjatic Sacha , Patton David , Lee J. Jack , Adam Stacey J. , Moravec Radim , Liu Xiaole Shirley , Cerami Ethan , Lindsay James , Tang Ming , Hodi F. Stephen , Wu Catherine J. , Wistuba Ignacio I. , Al-Atrash Gheath , Bernatchez Chantale , Bendall Sean C. , Hewitt Stephen M. , Sharon Elad , Streicher Howard , Enos Rebecca A. , Bowman Melissa D. , Tatard-Leitman Valerie M. , Sanchez-Espiridion Beatriz , Ranasinghe Srinika , Pichavant Mina , Del Valle Diane M. , Yu Joyce , Janssens Sylvie , Peterson-Klaus Jenny , Rowe Cathy , Bongers Gerold , Jenq Robert R. , Chang Chia-Chi , Abrams Jeffrey S. , Mooney Margaret , Doroshow James H. , Harris Lyndsay N. , Thurin Magdalena 
Published: January 2021

AbstractPurpose:Immunoprofiling to identify biomarkers and integration with clinical trial outcomes are critical to improving immunotherapy approaches for patients with cancer. However, the translational potential of individual studies is often limited by small sample size of trials and the complexity of immuno-oncology biomarkers. Variability in assay performance further limits comparison and interpretation of data across studies and laboratories.Experimental Design:To enable a systematic approach to biomarker identification and correlation with clinical outcome across trials, the Cancer Immune Monitoring and Analysis Centers and Cancer Immunologic Data Commons (CIMAC-CIDC) Network was established through support of the Cancer MoonshotSM Initiative of the National Cancer Institute (NCI) and the Partnership for Accelerating Cancer Therapies (PACT) with industry partners via the Foundation for the NIH.Results:The CIMAC-CIDC Network is composed of four academic centers with multidisciplinary expertise in cancer immunotherapy that perform validated and harmonized assays for immunoprofiling and conduct correlative analyses. A data coordinating center (CIDC) provides the computational expertise and informatics platforms for the storage, integration, and analysis of biomarker and clinical data.Conclusions:This overview highlights strategies for assay harmonization to enable cross-trial and cross-site data analysis and describes key elements for establishing a network to enhance immuno-oncology biomarker development. These include an operational infrastructure, validation and harmonization of core immunoprofiling assays, platforms for data ingestion and integration, and access to specimens from clinical trials. Published in the same volume are reports of harmonization for core analyses: whole-exome sequencing, RNA sequencing, cytometry by time of flight, and IHC/immunofluorescence.
The Tumor Microenvironment Impairs Th1 IFNγ Secretion through Alternative Splicing Modifications of Irf1 Pre-mRNA
Authors: Bernard Antoine , Hibos Christophe , Richard Corentin , Viltard Etienne , Chevrier Sandy , Lemoine Sophie , Melin Joséphine , Humblin Etienne , Mary Romain , Accogli Théo , Chalmin Fanny , Bruchard Mélanie , Peixoto Paul , Hervouet Eric , Apetoh Lionel , Ghiringhelli François , Végran Frédérique , Boidot Romain 
Published: January 2021

Abstract
It is clearly established that the immune system can affect cancer response to therapy. However, the influence of the tumor microenvironment (TME) on immune cells is not completely understood. In this respect, alternative splicing is increasingly described to affect the immune system. Here, we showed that the TME, via a TGFβ-dependent mechanism, increased alternative splicing events and induced the expression of an alternative isoform of the IRF1 transcription factor (IRF1Δ7) in Th1 cells. We found that the SFPQ splicing factor (splicing factor, proline- and glutamine-rich) was responsible for the IRF1Δ7 production. We also showed, in both mice and humans, that the IRF1 alternative isoform altered the full-length IRF1 transcriptional activity on the Il12rb1 promoter, resulting in decreased IFNγ secretion in Th1 cells. Thus, the IRF1Δ7 isoform was increased in the TME, and inhibiting IRF1Δ7 expression could potentiate Th1 antitumor responses.
Dynamic expression of brain functional systems disclosed by
fine-scale analysis of edge time series
Authors: Sporns Olaf , Faskowitz Joshua , Teixeira Andreia Sofia , Cutts Sarah A. , Betzel Richard F. 
Published: January 2021

Abstract
Functional connectivity (FC) describes the statistical dependence between neuronal populations or brain regions in resting-state fMRI studies and is commonly estimated as the Pearson correlation of time courses. Clustering or community detection reveals densely coupled sets of regions constituting resting-state networks or functional systems. These systems manifest most clearly when FC is sampled over longer epochs but appear to fluctuate on shorter timescales. Here, we propose a new approach to reveal temporal fluctuations in neuronal time series. Unwrapping FC signal correlations yields pairwise co-fluctuation time series, one for each node pair or edge, and allows tracking of fine-scale dynamics across the network. Co-fluctuations partition the network, at each time step, into exactly two communities. Sampled over time, the overlay of these bipartitions, a binary decomposition of the original time series, very closely approximates functional connectivity. Bipartitions exhibit characteristic spatiotemporal patterns that are reproducible across participants and imaging runs, capture individual differences, and disclose fine-scale temporal expression of functional systems. Our findings document that functional systems appear transiently and intermittently, and that FC results from the overlay of many variable instances of system expression. Potential applications of this decomposition of functional connectivity into a set of binary patterns are discussed.
Towards a Uniform and Informed Interpretation of the Best Interests of the Child by the Judiciary: Inter-American and European Jurisprudence
Authors: Sanz-Caballero Susana 
Published: January 2021

Abstract
This article analyses the interpretations made by two regional human rights courts regarding the best interests of the child. In cases of controversy, it is for the judges to decide how, or whether, the best interests of the child should be applied. Due to the dependence and vulnerability of children, judicial remedies are a critical form of redress when children’s rights are violated. This article analyses case law from two regional courts (the Inter-American Court of Human Rights (ICtHR) and the European Court of Human Rights (ECtHR)). The purpose of this analysis is twofold: first of all to see how the two courts interpret and apply the concept; and secondly, to ascertain whether there are similarities of interpretation or common grounds of understanding between the two courts, with particular regard to General Comment No. 14 (GC 14) of the United Nations Committee on the Rights of the Child on the right of the child to have their best interests taken as a primary consideration.
Dynamic Control of the Dominant Modes of Interannual Variability of Snowfall Frequency in China
Authors: Sun Bo , Wang Huijun , Wu Biwen , Xu Min , Zhou Botao , Li Huixin , Wang Teng 
Published: January 2021

AbstractThis study investigates the first two leading modes of the interannual variability of frequency of snowfall events (FSE) over China in the winter during 1986–2018. The positive phase of the first leading mode (EOF1) is mainly characterized by positive FSE anomalies in northeastern–northwestern China and negative FSE anomalies in the three-river-source region. In contrast, the positive phase of the second leading mode (EOF2) is mainly characterized by positive FSE anomalies in central-eastern China (CEC). EOF1 is affected by the synoptic-scale wave activity over the midlatitudes of the East Asian continent, where active synoptic-scale wave activity over the midlatitudes may cause increased FSE over northeastern–northwestern China, and vice versa. In a winter of a negative phase of the North Atlantic Oscillation, an anomalous deep cold low may occur over Siberia, which may induce increased meridional air temperature gradient, increased atmospheric baroclinicity, and hence increased FSE over the midlatitudes of the East Asian continent. The EOF2 is affected by the interaction between anomalous northerly cold advection and anomalous southerly water vapor transport over CEC. The positive phase of EOF2 is associated with negative sea ice anomalies in the Barents Sea–Kara Sea region and negative sea surface temperature anomalies in the central-eastern tropical Pacific. Reduced sea ice in the Barents Sea–Kara Sea during January–February may cause increased northerly cold advection over CEC, while a La Niña–like condition during January may induce southerly water vapor transport anomalies over CEC.
How Much Arctic Fresh Water Participates in the Subpolar Overturning Circulation?
Authors: Le Bras Isabela , Straneo Fiamma , Muilwijk Morven , Smedsrud Lars H. , Li Feili , Lozier M. Susan , Holliday N. Penny 
Published: January 2021

AbstractFresh Arctic waters flowing into the Atlantic are thought to have two primary fates. They may be mixed into the deep ocean as part of the overturning circulation, or flow alongside regions of deep water formation without impacting overturning. Climate models suggest that as increasing amounts of freshwater enter the Atlantic, the overturning circulation will be disrupted, yet we lack an understanding of how much freshwater is mixed into the overturning circulation’s deep limb in the present day. To constrain these freshwater pathways, we build steady-state volume, salt, and heat budgets east of Greenland that are initialized with observations and closed using inverse methods. Freshwater sources are split into oceanic Polar Waters from the Arctic and surface freshwater fluxes, which include net precipitation, runoff, and ice melt, to examine how they imprint the circulation differently. We find that 65 mSv (1 Sv ≡ 106 m3 s−1) of the total 110 mSv of surface freshwater fluxes that enter our domain participate in the overturning circulation, as do 0.6 Sv of the total 1.2 Sv of Polar Waters that flow through Fram Strait. Based on these results, we hypothesize that the overturning circulation is more sensitive to future changes in Arctic freshwater outflow and precipitation, while Greenland runoff and iceberg melt are more likely to stay along the coast of Greenland.
Hydrothermal solidification of sepiolite into a cemented sepiolite aggregate for humidity regulation and formaldehyde removal
Authors: Qiu Pengcheng , Guo Li , Qi Yujie , Cheng Mingzhao , Jing Zhenzi 
Published: January 2021

AbstractSepiolite powder was hydrothermally solidified into a cemented, designed to function both in humidity regulation and volatile organic compound (VOC) removal. The solidification process mimicked the cementation of sedimentary rocks. The formation of the calcium aluminium silicate hydrate (C-A-S-H) or Al-tobermorite enhanced the strength (maximum flexural strength >17 MPa) and improved the porosity of the solidified materials. Due to the low temperature of hydrothermal solidification (≤473.15 K), most sepiolite remained in the matrix of the solidified specimens. The cemented sepiolite aggregate shows outstanding humidity-regulating performance (moisture adsorption of 430 g m–2), and the synergistic effects of the residual sepiolite and neoformed Al-tobermorite exerted a positive influence on the humidity regulation performance of the material. Similarly to the behaviour of sepiolite, the solidified material also displayed good formaldehyde-removal capacity (60–68%). The pore dimensions controlled the humidity regulation and formaldehyde removal. The humidity regulation depends on the mesopores, which originate mainly from both the original sepiolite and the neoformed C-A-S-H phases and Al-tobermorite, while the formaldehyde removal depends on the micropores from the original sepiolite in the matrix. As such, the cemented sepiolite aggregate might be hydrothermally synthesized and might be used to improve the comfort and safety of indoor environments for human beings.
Medullary stromal cells synergize their production and capture of CCL21 for T-cell emigration from neonatal mouse thymus
Authors: James Kieran D. , Legler Daniel F. , Purvanov Vladimir , Ohigashi Izumi , Takahama Yousuke , Parnell Sonia M. , White Andrea J. , Jenkinson William E. , Anderson Graham 
Published: January 2021

AbstractThe release of newly selected αβT cells from the thymus is key in establishing a functional adaptive immune system. Emigration of the first cohorts of αβT cells produced during the neonatal period is of particular importance, because it initiates formation of the peripheral αβT-cell pool and provides immune protection early in life. Despite this, the cellular and molecular mechanisms of thymus emigration are poorly understood. We examined the involvement of diverse stromal subsets and individual chemokine ligands in this process. First, we demonstrated functional dichotomy in the requirement for CCR7 ligands and identified CCL21, but not CCL19, as an important regulator of neonatal thymus emigration. To explain this ligand-specific requirement, we examined sites of CCL21 production and action and found Ccl21 gene expression and CCL21 protein distribution occurred within anatomically distinct thymic areas. Although Ccl21 transcription was limited to subsets of medullary epithelium, CCL21 protein was captured by mesenchymal stroma consisting of integrin α7+ pericytes and CD34+ adventitial cells at sites of thymic exit. This chemokine compartmentalization involved the heparan sulfate–dependent presentation of CCL21 via its C-terminal extension, explaining the absence of a requirement for CCL19, which lacks this domain and failed to be captured by thymic stroma. Collectively, we identified an important role for CCL21 in neonatal thymus emigration, revealing the importance of this chemokine in initial formation of the peripheral immune system. Moreover, we identified an intrathymic mechanism involving cell-specific production and presentation of CCL21, which demonstrated a functional synergy between thymic epithelial and mesenchymal cells for αβT-cell emigration.