bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Multipotent Adult Progenitor Cells Effectively Reduce Graft-vs-Host Disease While Preserving Graft-Vs-Leukemia Activity
Authors: Metheny Leland , Eid Saada , Wuttisarnwattana Patiwet , Auletta Jeffery J. , Liu Chen , Van Dervort Alana , Paez Conner , Lee ZhengHong , Wilson David , Lazarus Hillard M. , Deans Robert , Vant Hof Wouter , Ktena Yiouli , Cooke Kenneth R. 
Published: November 2021

Abstract
Graft-vs-host disease (GvHD) limits successful outcomes following allogeneic blood and marrow transplantation (allo-BMT). We examined whether the administration of human, bone marrow-derived, multipotent adult progenitor cells (MAPCs™) could regulate experimental GvHD. The immunoregulatory capacity of MAPC cells was evaluated in vivo using established murine GvHD models. Injection of MAPC cells on day +1 (D1) and +4 (D4) significantly reduced T-cell expansion and the numbers of donor-derived, Tumor Necrosis Factor Alpha (TNFα) and Interferon Gamma (IFNγ)-producing, CD4+ and CD8+ cells by D10 compared with untreated controls. These findings were associated with reductions in serum levels of TNFα and IFNγ, intestinal and hepatic inflammation and systemic GvHD as measured by survival and clinical score. Biodistribution studies showed that MAPC cells tracked from the lung and to the liver, spleen, and mesenteric nodes within 24 hours after injection. MAPC cells inhibited mouse T-cell proliferation in vitro and this effect was associated with reduced T-cell activation and inflammatory cytokine secretion and robust increases in the concentrations of Prostaglandin E2 (PGE2) and Transforming Growth Factor Beta (TGFβ). Indomethacin and E-prostanoid 2 (EP2) receptor antagonism both reversed while EP2 agonism restored MAPC cell-mediated in vitro T-cell suppression, confirming the role for PGE2. Furthermore, cyclo-oxygenase inhibition following allo-BMT abrogated the protective effects of MAPC cells. Importantly, MAPC cells had no effect on the generation cytotoxic T lymphocyte activity in vitro, and the administration of MAPC cells in the setting of leukemic challenge resulted in superior leukemia-free survival. Collectively, these data provide valuable information regarding the biodistribution and regulatory capacity of MAPC cells, which may inform future clinical trial design.
Downregulation of Augmenter of Liver Regeneration Impairs the Therapeutic Efficacy of Liver Epithelial Progenitor Cells Against Acute Liver Injury by Enhancing Mitochondrial Fission
Authors: Dong Yuan , Kong Weining , An Wei 
Published: November 2021

Abstract
Cell-based therapeutic approaches have been proven to be effective strategies for the treatment of acute liver injury (ALI). However, widespread application of these procedures is limited by several key issues, including rapid loss of stemness in vitro, aberrant differentiation into undesirable cell types, and low engraftment in vivo. In this study, liver epithelial progenitor cells (LEPCs) were characterized and transfected with augmenter of liver regeneration (ALR). The results revealed that in ALI mice with CCl4, the transplantation of ALR-bearing LEPCs into the liver markedly protected mice against ALI by decreasing the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), thus relieving hepatic tissue injury and attenuating inflammatory infiltration. Mechanistically, the knockdown of ALR in LEPCs activated the phosphorylation of dynamin-related protein 1 (Drp1) at the S616 site and thereby enhanced mitochondrial fission. In contrast, the transfection of ALR into LEPCs significantly inhibited Drp1 phosphorylation, thereby favoring the maintenance of mitochondrial integrity and the preservation of adenosine triphosphate contents in LEPCs. Consequently, the ALR-bearing LEPCs transplanted into ALI mice exhibited substantially greater homing ability to the injured liver via the SDF-1/CXCR4 axis than that of LEPCs-lacking ALR. In conclusion, we demonstrated that the transplantation of ALR-transfected LEPCs protected mice against CCl4-induced ALI, thus offering immense curative potential in the clinic.
State-Of-Play for Cellular Therapies in Cardiac Repair and Regeneration
Authors: Vaka Ramana , Davis Darryl R. 
Published: November 2021

Abstract
Cardiovascular disease is the primary cause of death around the world. For almost two decades, cell therapy has been proposed as a solution for heart disease. In this article, we report on the “state-of-play” of cellular therapies for cardiac repair and regeneration. We outline the progression of new ideas from the preclinical literature to ongoing clinical trials. Recent data supporting the mechanics and mechanisms of myogenic and paracrine therapies are evaluated in the context of long-term cardiac engraftment. This discussion informs on promising new approaches to indicate future avenues for the field.
Design‐oriented elasto‐plastic analysis of reinforced concrete structures with in‐plane forces applying convex optimization
Authors: Vestergaard Daniel , Larsen Kasper Paaske , Hoang Linh Cao , Poulsen Peter Noe , Feddersen Bent 
Published: November 2021

AbstractAssessment of the cracked behavior at service load and verification of sufficient deformation capacity in the ultimate state are often required when designing reinforced concrete structures. Most existing methods dedicated to nonlinear analysis of reinforced concrete, however, are not well‐suited in practice for use in design processes involving large‐scale structural problems due to an enormous modeling effort and lack of numerical stability. This paper presents a new finite element framework for efficient elasto‐plastic analysis of two‐dimensional reinforced concrete structures subjected to in‐plane forces. The basic concept is to adopt a stress‐based finite element formulation and cast the problem as a convex optimization problem where energy principles are invoked through a formalistic application of nonlinear‐elastic material models. The method accounts for reinforcement yielding and concrete crushing, including the strength reduction due to cracking, and can be used to imitate the elasto‐plastic response of fully‐cracked structures subjected to monotonic loading. The efficiency of the method is demonstrated, inter alia, by an analysis of a complex structure, where the discretized problem has more than 1 million variables and is solved within a few minutes on a standard personal computer.
Enhanced dielectric performance of polydimethylsiloxane‐based ternary composites films via tailored hydrogen bonds between carbon nanotube and barium titanate as modified fillers
Authors: Tang Yaokai , Liu Hongfu , Wang Xincheng , Cheng Shangru , Gao Qiangmin , Liu Jiwen , Guan Shanshan , Zhao Shugao 
Published: November 2021

AbstractA series of BT–cCNT/PDMS and BT–aCNT/PDMS composites were developed by incorporating barium titanate (BT) nanoparticles together with carboxylic functionalized multiwalled carbon nanotubes (cCNT) and amino functionalization multiwalled carbon nanotubes (aCNT) in polydimethylsiloxane (PDMS). Benefitting from the abundant active groups, CNTs and BTs can be in situ “bridged” by hydrogen bond in all of the BT–cCNT/PDMS and BT–aCNT/PDMS composites. Here, we studied the effect of hydrogen bonds (type and amount) between BTs and CNTs at the interface and dielectric properties of the composites. The results indicated that the BT–cCNT/PDMS composite exhibited higher dielectric constant and comparable dielectric loss than the BT–aCNT/PDMS composite, especially when weightCNT < 1 wt%. Also, the dielectric properties of BT–cCNT/PDMS composite show stronger temperature dependence than BT–aCNT/PDMS composite. Finally, the tailorable performance of the polymer‐based dielectric composites can be obtained by regulating the interface with the help of hydrogen bonds.
Flood legislation and land policy framework of EU and non‐EU countries in Southern Europe
Authors: Kapović Solomun Marijana , Ferreira Carla S. S. , Zupanc Vesna , Ristić Ratko , Drobnjak Aleksandar , Kalantari Zahra 
Published: November 2021

AbstractFloods are a widespread natural hazard affecting people and their assets in regions worldwide, including Southern Europe. Besides coastal floods, the Mediterranean region is highly prone to flash floods driven by short but intense precipitation events. With increasing flood risk due to climate change and socio‐economic conditions, governments are under pressure to reinforce flood protection measures, which could be a great challenge for the weak economies of non‐EU developing countries. This is of particular relevance to achieving international commitments such as the United Nations Sustainable Development Goals. Several policy frameworks have been developed to mitigate flooding risk, at European Union (EU) and global level. These frameworks call for a holistic risk reduction approach where governments, institutions, and households are all responsible for reducing risk. In practice, however, gray infrastructure remains the prevailing flood risk management measure in many countries. Incorporation into national legislation and implementation of the EU policy framework will increase constraints and pressures for non‐EU countries, particularly those strongly committed to becoming EU members in future. This article provides a comprehensive review of policies and measures implemented in four different southern European countries to mitigate flood hazard, and compares governance aspects between EU (Portugal and Slovenia) and non‐EU countries (B&H and Serbia). Understanding governance aspects and the status of flood‐related policy implementation is of critical importance in protecting people and enhancing resilience to climate change impacts. Programs of improvement measures and further integration of sustainable water management with other sectoral policies are required to reduce flood risks.This article is categorized under:
Engineering Water > Planning Water
Human Water > Water Governance
Science of Water > Water Extremes
Chapter 3: The Role of Food Exports in Russia’s Economy
Authors: Svetlov Nikolai M. 
Published: November 2021

AbstractAs Russia’s agri-food exports have increased in recent years, the role of food exports has evolved from being negligible at the beginning of the 2000s to almost 30 percent of agricultural production in recent years. Agri-food exports account for a substantial amount of growth in the agricultural sector. The contribution of food exports to the national economy, however, is minor. Food exports’ net contribution to the national budget is about zero. Technical advances suggest that the role of agricultural exports in the national economy will keep gradually growing but will remain a secondary factor in national welfare.
Chapter 5: Russia’s Role in International Fish and Seafood Trade
Authors: Nilssen Frode 
Published: November 2021

AbstractThis chapter sheds light on Russia’s changed role in the international seafood trade system and discusses to what extent the new more export-oriented turn is sustainable. Russia’s seafood trade policy has changed significantly over time, from directing just about all of the production to the domestic market during the Soviet period, to increasingly pursuing a dual strategy as both an importer and exporter from 2000 onwards. The first section gives a brief account of Soviet-era seafood production and trade. The second part offers a perspective on seafood trade during the early post-Soviet period. The third part examines how the introduction of Food Security Doctrines and the 2014 embargo have influenced Russia’s seafood trade. The final section provides an outlook for the future. Similar to agriculture, concerns over food security are likely to lead to a reduced role as a seafood importer and a larger role as a seafood exporter. The structure of Russia’s seafood exports will continue to tilt towards Asian markets, with European markets assuming a secondary role.
Conversion of viridicatic acid to crustosic acid by cytochrome P450 enzyme-catalysed hydroxylation and spontaneous cyclisation
Authors: Zhou Jenny , Li Shu-Ming 
Published: November 2021

Abstract
Cytochrome P450 monooxygenases (P450s) are considered nature’s most versatile catalysts and play a crucial role in regio- and stereoselective oxidation reactions on a broad range of organic molecules. The oxyfunctionalisation of unactivated carbon-hydrogen (C-H) bonds, in particular, represents a key step in the biosynthesis of many natural products as it provides substrates with increased reactivity for tailoring reactions. In this study, we investigated the function of the P450 enzyme TraB in the terrestric acid biosynthetic pathway. We firstly deleted the gene coding for the DNA repair subunit protein Ku70 by using split marker-based deletion plasmids for convenient recycling of the selection marker to improve gene targeting in Penicillium crustosum. Hereby, we reduced ectopic DNA integration and facilitated genetic manipulation in P. crustosum. Afterward, gene deletion in the Δku70 mutant of the native producer P. crustosum and heterologous expression in Aspergillus nidulans with precursor feeding proved the involvement of TraB in the formation of crustosic acid by catalysing the essential hydroxylation reaction of viridicatic acid.

Key points
•Deletion of Ku70 by using split marker approach for selection marker recycling.
•Functional identification of the cytochrome P450 enzyme TraB.
•Fulfilling the reaction steps in the terrestric acid biosynthesis.
Emergency Neurosurgery Performed by General Surgeons: A Systematic Review
Authors: Hewitt Joseph N. , Ovenden Christopher D. , Glynatsis John M. , Sabab Ahad , Gupta Aashray K. , Kovoor Joshua G. , Wells Adam J. , Maddern Guy J. 
Published: November 2021

AbstractBackgroundIn under‐resourced settings, general surgeons may be called upon to perform emergency operations within other specialties. Accordingly, we aimed to characterise patient outcomes after emergency neurosurgery performed by a general surgeon or general surgery trainee.MethodsPubMed, Embase and the Cochrane Library were searched to 30 May 2021 for observational studies reporting outcomes after emergency neurosurgery performed by a general surgeon. Study screening, data extraction, and risk of bias using the Downs and Black checklist were performed in duplicate. Data on setting, operation undertaken, mortality rates and complications were extracted. Meta‐analysis was planned but not possible due to heterogeneity. This study is registered with PROSPERO, CRD42021258097.ResultsFrom 632 records, 14 retrospective observational studies were included, covering a total sample of 1,988 operations. Four studies were from Australia, and the remaining 10 were, respectively, from 10 other countries. Most common operations performed were decompressive surgery with burr holes or craniectomy for head trauma and insertion of intracranial pressure monitors. Rural hospitals were the most common settings. Mortality rates for procedures performed by general surgeons at latest follow‐up were heterogenous, ranging from 5% for evacuation of chronic subdural haematoma in Kenya to 81% in head injured patients in a Hong Kong study.ConclusionsThis is the first systematic review that synthesises the literature to characterise patient outcomes after neurosurgical operations performed by a general surgeon. Findings from this study may benefit global surgery performed in rural, remote, military or humanitarian settings.
Effect of the perception of breakfast consumption on subsequent appetite and energy intake in healthy males
Authors: Slater Tommy , Mode William J. A. , Hough John , James Ruth M. , Sale Craig , James Lewis J. , Clayton David J. 
Published: November 2021

Abstract
Purpose
This study aimed to assess the effects of consuming a very-low-energy placebo breakfast on subsequent appetite and lunch energy intake.

Methods
Fourteen healthy males consumed water-only (WAT), very-low-energy, viscous placebo (containing water, low-calorie flavoured squash, and xanthan gum; ~ 16 kcal; PLA), and whole-food (~ 573 kcal; FOOD) breakfasts in a randomised order. Subjects were blinded to the energy content of PLA and specific study aims. Venous blood samples were collected pre-breakfast, 60- and 180-min post-breakfast to assess plasma acylated ghrelin and peptide tyrosine tyrosine concentrations. Subjective appetite was measured regularly, and energy intake was assessed at an ad libitum lunch meal 195-min post-breakfast.

Results
Lunch energy intake was lower during FOOD compared to WAT (P < 0.05), with no further differences between trials (P ≥ 0.132). Cumulative energy intake (breakfast plus lunch) was lower during PLA (1078 ± 274 kcal) and WAT (1093 ± 249 kcal), compared to FOOD (1554 ± 301 kcal; P < 0.001). Total area under the curve (AUC) for hunger, desire to eat and prospective food consumption were lower, and fullness was greater during PLA and FOOD compared to WAT (P < 0.05). AUC for hunger was lower during FOOD compared to PLA (P < 0.05). During FOOD, acylated ghrelin was suppressed compared to PLA and WAT at 60 min (P < 0.05), with no other hormonal differences between trials (P ≥ 0.071).

Conclusion
Consuming a very-low-energy placebo breakfast does not alter energy intake at lunch but may reduce cumulative energy intake across breakfast and lunch and attenuate elevations in subjective appetite associated with breakfast omission.

Trial registration
NCT04735783, 2nd February 2021, retrospectively registered.
EZHIP: a new piece of the puzzle towards understanding pediatric posterior fossa ependymoma
Authors: Jenseit Anne , Camgöz Aylin , Pfister Stefan M. , Kool Marcel 
Published: November 2021

AbstractEpendymomas (EPN) are tumors of the central nervous system (CNS) that can arise in the supratentorial brain (ST-EPN), hindbrain or posterior fossa (PF-EPN) or anywhere in the spinal cord (SP-EPN), both in children and adults. Molecular profiling studies have identified distinct groups and subtypes in each of these anatomical compartments. In this review, we give an overview on recent findings and new insights what is driving PFA ependymomas, which is the most common group. PFA ependymomas are characterized by a young median age at diagnosis, an overall balanced genome and a bad clinical outcome (56% 10-year overall survival). Sequencing studies revealed no fusion genes or other highly recurrently mutated genes, suggesting that the disease is epigenetically driven. Indeed, recent findings have shown that the characteristic global loss of the repressive histone 3 lysine 27 trimethylation (H3K27me3) mark in PFA ependymoma is caused by aberrant expression of the enhancer of zeste homolog inhibitory protein (EZHIP) or in rare cases by H3K27M mutations, which both inhibit EZH2 thereby preventing the polycomb repressive complex 2 (PRC2) from spreading H3K27me3. We present the current status of the ongoing work on EZHIP and its essential role in the epigenetic disturbance of PFA biology. Comparisons to the oncohistone H3K27M and its role in diffuse midline glioma (DMG) are drawn, highlighting similarities but also differences between the tumor entities and underlying mechanisms. A strong focus is to point out missing information and to present directions of further research that may result in new and improved therapies for PFA ependymoma patients.
Regulation of dhurrin pathway gene expression during Sorghum bicolor development
Authors: Gleadow Roslyn M. , McKinley Brian A. , Blomstedt Cecilia K. , Lamb Austin C. , Møller Birger Lindberg , Mullet John E. 
Published: November 2021

Abstract
Main conclusion
Developmental and organ-specific expression of genes in dhurrin biosynthesis, bio-activation, and recycling offers dynamic metabolic responses optimizing growth and defence responses in Sorghum.

Abstract
Plant defence models evaluate the costs and benefits of resource investments at different stages in the life cycle. Poor understanding of the molecular regulation of defence deployment and remobilization hampers accuracy of the predictions. Cyanogenic glucosides, such as dhurrin are phytoanticipins that release hydrogen cyanide upon bio-activation. In this study, RNA-seq was used to investigate the expression of genes involved in the biosynthesis, bio-activation and recycling of dhurrin in Sorghum bicolor. Genes involved in dhurrin biosynthesis were highly expressed in all young developing vegetative tissues (leaves, leaf sheath, roots, stems), tiller buds and imbibing seeds and showed gene specific peaks of expression in leaves during diel cycles. Genes involved in dhurrin bio-activation were expressed early in organ development with organ-specific expression patterns. Genes involved in recycling were expressed at similar levels in the different organ during development, although post-floral initiation when nutrients are remobilized for grain filling, expression of GSTL1 decreased > tenfold in leaves and NITB2 increased > tenfold in stems. Results are consistent with the establishment of a pre-emptive defence in young tissues and regulated recycling related to organ senescence and increased demand for nitrogen during grain filling. This detailed characterization of the transcriptional regulation of dhurrin biosynthesis, bioactivation and remobilization genes during organ and plant development will aid elucidation of gene regulatory networks and signalling pathways that modulate gene expression and dhurrin levels. In-depth knowledge of dhurrin metabolism could improve the yield, nitrogen use efficiency and stress resilience of Sorghum.
CXCL13 is expressed in a subpopulation of neuroendocrine cells in the murine trachea and lung
Authors: Mahmoud Wafaa , Perniss Alexander , Poharkar Krupali , Soultanova Aichurek , Pfeil Uwe , Hoek Andreas , Bhushan Sudhanshu , Hain Torsten , Gärtner Ulrich , Kummer Wolfgang 
Published: November 2021

AbstractThe conducting airways are lined by distinct cell types, comprising basal, secretory, ciliated, and rare cells, including ionocytes, solitary cholinergic chemosensory cells, and solitary and clustered (neuroepithelial bodies) neuroendocrine cells. Airway neuroendocrine cells are in clinical focus since they can give rise to small cell lung cancer. They have been implicated in diverse functions including mechanosensation, chemosensation, and regeneration, and were recently identified as regulators of type 2 immune responses via the release of the neuropeptide calcitonin gene-related peptide (CGRP). We here assessed the expression of the chemokine CXCL13 (B cell attracting chemokine) by these cells by RT-PCR, in silico analysis of publicly available sequencing data sets, immunohistochemistry, and immuno-electron microscopy. We identify a phenotype of neuroendocrine cells in the naïve mouse, producing the chemokine CXCL13 predominantly in solitary neuroendocrine cells of the tracheal epithelium (approx. 70% CXCL13+) and, to a lesser extent, in the solitary neuroendocrine cells and neuroepithelial bodies of the intrapulmonary bronchial epithelium (< 10% CXCL13+). In silico analysis of published sequencing data of murine tracheal epithelial cells was consistent with the results obtained by immunohistochemistry as it revealed that neuroendocrine cells are the major source of Cxcl13-mRNA, which was expressed by 68–79% of neuroendocrine cells. An unbiased scRNA-seq data analysis of overall gene expression did not yield subclusters of neuroendocrine cells. Our observation demonstrates phenotypic heterogeneity of airway neuroendocrine cells and points towards a putative immunoregulatory role of these cells in bronchial-associated lymphoid tissue formation and B cell homeostasis.
On the lower bound of the principal eigenvalue of a nonlinear operator
Authors: Tu Yucheng 
Published: November 2021

AbstractWe prove sharp lower bound estimates for the first nonzero eigenvalue of the non-linear elliptic diffusion operator $$L_p$$

L
p

on a smooth metric measure space, without boundary or with a convex boundary and Neumann boundary condition, satisfying $$BE(\kappa ,N)$$

B
E
(
κ
,
N
)

for $$\kappa \ne 0$$

κ
≠
0

. Our results extends the work of Koerber Valtorta (Calc Vari Partial Differ Equ. 57(2), 49 2018) for case $$\kappa =0$$

κ
=
0

and Naber–Valtorta (Math Z 277(3–4):867–891, 2014) for the p-Laplacian.