bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hydroxylapatite-collagen hybrid scaffold induces human adipose-derived mesenchymal stem cells to osteogenic differentiation in vitro and bone regrowth in patients
Authors: Mazzoni Elisa , D'Agostino Antonio , Iaquinta Maria Rosa , Bononi Ilaria , Trevisiol Lorenzo , Rotondo John Charles , Patergnani Simone , Giorgi Carlotta , Gunson Michael J. , Arnett G. William , Nocini Pier Francesco , Tognon Mauro , Martini Fernanda 
Published: December 2019

AbstractTissue engineering-based bone graft is an emerging viable treatment modality to repair and regenerate tissues damaged as a result of diseases or injuries. The structure and composition of scaffolds should modulate the classical osteogenic pathways in human stem cells. The osteoinductivity properties of the hydroxylapatite-collagen hybrid scaffold named Coll/Pro Osteon 200 were investigated in an in vitro model of human adipose mesenchymal stem cells (hASCs), whereas the clinical evaluation was carried out in maxillofacial patients. Differentially expressed genes (DEGs) induced by the scaffold were analyzed using the Osteogenesis RT2 PCR Array. The osteoinductivity potential of the scaffold was also investigated by studying the alkaline phosphatase (ALP) activity, matrix mineralization, osteocalcin (OCN), and CLEC3B expression protein. Fifty patients who underwent zygomatic augmentation and bimaxillary osteotomy were evaluated clinically, radiologically, and histologically during a 3-year follow-up. Among DEGs, osteogenesis-related genes, including BMP1/2, ALP, BGLAP, SP7, RUNX2, SPP1, and EGFR, which play important roles in osteogenesis, were found to be upregulated. The genes to cartilage condensation SOX9, BMPR1B, and osteoclast cells TNFSF11 were detected upregulated at every time point of the investigation. This scaffold has a high osteoinductivity revealed by the matrix mineralization, ALP activity, OCN, and CLEC3B expression proteins. Clinical evaluation evidences that the biomaterial promotes bone regrowth. Histological results of biopsy specimens from patients showed prominent ossification. Experimental data using the Coll/Pro Osteon 200 indicate that clinical evaluation of bone regrowth in patients, after scaffold implantation, was supported by DEGs implicated in skeletal development as shown in “in vitro” experiments with hASCs.Significance statement Bone regrowth can be achieved using different scaffolds. Biomaterials provide structural and biological cues to stem cells to stimulate the osteogenic differentiation. The new knowledge on the mechanisms of bone repair is of paramount importance to address significant steps needed in translational and precise medicine to cure patients. The hybrid scaffold Pro Osteon200/Avitene Collagen showed a significant osteogenic induction. The continuous supply of human adipose-derived mesenchymal stem cells for bone regrowth/remodeling, chondrogenic, and osteoclast activities with their epigenetic modulations have been disclosed herein. The new data of this study indicate that the continuous expression of osteogenic, osteoclastic, and chondrogenic genes favors bone regrowth.
Transition‐Metal‐Free Activation of Amides by N−C Bond Cleavage
Authors: Li Guangchen , Szostak Michal 
Published: December 2019

AbstractThe amide bond N−C activation represents a powerful strategy in organic synthesis to functionalize the historically inert amide linkage. This personal account highlights recent remarkable advances in transition‐metal‐free activation of amides by N−C bond cleavage, focusing on both (1) mechanistic aspects of ground‐state‐destabilization of the amide bond enabling formation of tetrahedral intermediates directly from amides with unprecedented selectivity, and (2) synthetic utility of the developed transformations. Direct nucleophilic addition to amides enables a myriad of powerful methods for the formation of C−C, C−N, C−O and C−S bonds, providing a straightforward and more synthetically useful alternative to acyl‐metals.
Metallacycle Transfer and its Link to Light‐Emitting Materials and Conjugated Polymers
Authors: Rivard Eric 
Published: December 2019

AbstractMajor advances in optoelectronic technologies (e. g., solar cells, organic light‐emitting diodes, etc…) are prefaced by the discovery of new synthetic methodologies. In this review, the key role of the Fagan‐Nugent reaction in enabling our team (and others) to gain access to new building blocks for luminescent materials and conjugated polymers bearing p‐block elements will be described. The Fagan‐Nugent reaction is extremely powerful as a synthetic tool since the efficient zirconium‐element atom exchange involved affords a wide range of unsaturated inorganic heterocycles of controllable composition and function.
Clinical and genetic correlates of islet-autoimmune signatures in juvenile-onset type 1 diabetes
Authors: Claessens Laura A. , Wesselius Joris , van Lummel Menno , Laban Sandra , Mulder Flip , Mul Dick , Nikolic Tanja , Aanstoot Henk-Jan , Koeleman Bobby P. C. , Roep Bart O. 
Published: December 2019

Abstract
Aims/hypothesis
Heterogeneity in individuals with type 1 diabetes has become more generally appreciated, but has not yet been extensively and systematically characterised. Here, we aimed to characterise type 1 diabetes heterogeneity by creating immunological, genetic and clinical profiles for individuals with juvenile-onset type 1 diabetes in a cross-sectional study.

Methods
Participants were HLA-genotyped to determine HLA-DR-DQ risk, and SNP-genotyped to generate a non-HLA genetic risk score (GRS) based on 93 type 1 diabetes-associated SNP variants outside the MHC region. Islet autoimmunity was assessed as T cell proliferation upon stimulation with the beta cell antigens GAD65, islet antigen-2 (IA-2), preproinsulin (PPI) and defective ribosomal product of the insulin gene (INS-DRIP). Clinical parameters were collected retrospectively.

Results
Of 80 individuals, 67 had proliferation responses to one or more islet antigens, with vast differences in the extent of proliferation. Based on the multitude and amplitude of the proliferation responses, individuals were clustered into non-, intermediate and high responders. High responders could not be characterised entirely by enrichment for the highest risk HLA-DR3-DQ2/DR4-DQ8 genotype. However, high responders did have a significantly higher non-HLA GRS. Clinically, high T cell responses to beta cell antigens did not reflect in worsened glycaemic control, increased complications, development of associated autoimmunity or younger age at disease onset. The number of beta cell antigens that an individual responded to increased with disease duration, pointing to chronic islet autoimmunity and epitope spreading.

Conclusions/interpretation
Collectively, these data provide new insights into type 1 diabetes disease heterogeneity and highlight the importance of stratifying patients on the basis of their genetic and autoimmune signatures for immunotherapy and personalised disease management.
Invasiveness and Metastatic Aggressiveness in Small Differentiated Thyroid Cancers: Demography of Small Papillary Thyroid Carcinomas in the Swedish Population
Authors: Bayadsi Haytham , Bergman Martin , Sund Malin , Hennings Joakim 
Published: December 2019

AbstractBackgroundThe western world is seeing a rising incidence of thyroid cancer. Improved diagnostic methods do not entirely explain this increase. Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid cancer. Small PTC (≤20 mm) and especially papillary thyroid microcarcinomas (PTMC ≤10 mm) are considered to be low‐risk tumors but some cases are considerably more aggressive. Sufficient understanding of these mechanisms is a long‐term goal for more efficient and safer treatment of these tumors.MethodsWe identified 959 cases of small PTCs in the validated Scandinavian Quality Register for Thyroid, Parathyroid and Adrenal Surgery, grouped according to lymph node metastasis. These were analyzed according to age, gender, tumor size and geographic region.ResultsPatients with N1b disease (lateral lymph nodes metastases) had a smaller tumor size compared to patients with N1a disease (8.6 mm vs 10.1 mm respectively, p < 0.05). Patients and specifically females with N1b disease were younger than those with N0 or N1a disease. Patients with N1b disease had a lower proportion of females (60%) compared to N0 and N1a groups (81% and 78%, respectively). The incidence of operated small PTCs and of lymph node engagement differs between geographic regions in Sweden.ConclusionsSmall PTC and especially PTMC seem to show different patterns of aggressiveness and demography regarding lateral lymph node metastases and 7% had N1b disease and tumor <1 cm, underscoring the importance of lymph node evaluation in PTMC patients. More understanding of predictive factors, mechanisms for metastatic disease and causes of regional differences, is needed.
Protein energy wasting; what is it and what can we do to prevent it?
Authors: Rees Lesley 
Published: December 2019

AbstractSome children with declining height and BMI SDS fail to respond to optimisation of nutritional intake. As well as poor growth, they have muscle wasting and relative preservation of body fat. This is termed protein energy wasting (PEW). The process results from an interaction of chronic inflammation alongside poor nutritional intake. This review discusses the causes and potential preventative therapies for PEW.
Autonomes Demand Side Management verteilter Energiespeicher
Authors: Kepplinger Peter , Fässler Bernhard , Huber Gerhard , Ireshika Muhandiram Arachchige Subodha Thara , Rheinberger Klaus , Preißinger Markus 
Published: December 2019

ZusammenfassungVerbraucherseitige Laststeuerung (Demand Side Management – DSM) wird als ein möglicher Ansatz betrachtet, um die Auswirkungen des Ausbaus von fluktuierenden Erneuerbaren im Stromnetz auszugleichen. Sollen viele verteilte Energiesysteme damit angesprochen werden, stellen zentralistische Ansätze dabei hohe Anforderungen an die Kommunikationsinfrastruktur. Als Alternative wird vielfach eine autonome Laststeuerung (ADSM) mit anreizbasierter Optimierung direkt auf dem Verbrauchergerät betrachtet. Dabei kann die Anreizfunktion mittels unidirektionaler Kommunikation übertragen werden.Am Forschungszentrum Energie der Fachhochschule Vorarlberg wurden in den letzten Jahren Algorithmen und Prototypen für den Einsatz von ADSM auf verschiedensten verteilten Energiespeichern im elektrischen Stromnetz entwickelt. Dabei werden sowohl thermische Energiespeicher (z. B. Haushalts-Warmwasserspeicher) als auch elektrochemische Speicher (z. B. Batteriespeichersysteme oder Elektroautos) betrachtet. Außerdem werden die Auswirkungen solcher Systeme auf das elektrische Verteilnetz untersucht. Dieser Artikel gibt einen Überblick über die entwickelten Methoden und Ergebnisse aus diesem Forschungsfeld mit dem Ziel, ein weitreichendes Verständnis für die Chancen und Grenzen des ADSM zu schaffen.
Uncertainty of volume fraction in bimrock using the scan-line method and its application in the estimation of deformability parameters
Authors: Lu Yu-Chen , Tien Yong-Ming , Juang Charng Hsein , Lin Jeen-Shang 
Published: December 2019

AbstractThe volume fraction within a bimrock or bimsoil is an essential parameter that is useful for estimating the engineering properties of heterogeneous geomaterials. This paper presents analytical and numerical solutions to quantify the uncertainty of volume fraction measurements in bimrock/bimsoil using a scan-line method. The analytical solutions for the mean and variance of volume fraction estimates are based on a representative volume element model. The numerical solution is obtained through simulations of scan-line measurements. This work also employs physical tests using CT scan images from artificial bimrock/bimsoil to validate these solutions. The results demonstrate that the uncertainties of the volume fraction depend on the magnitude of the volume fraction of the blocks, the diameter of the blocks, and the length of the scan line. The proposed analytical and numerical solutions are compared with existing physical experimental tests and analytical solutions. An illustrative example to demonstrate the estimation of the uncertainty of volume fraction using the scan-line measurement is present. Finally, an example application of the volume fraction characterization in the geological engineering, in terms of Young’s modulus estimation and characterization, is provided.
Rigour and Intuition
Authors: Tatton-Brown Oliver 
Published: December 2019

AbstractThis paper sketches an account of the standard of acceptable proof in mathematics—rigour—arguing that the key requirement of rigour in mathematics is that nontrivial inferences be provable in greater detail. This account is contrasted with a recent perspective put forward by De Toffoli and Giardino, who base their claims on a case study of an argument from knot theory. I argue that De Toffoli and Giardino’s conclusions are not supported by the case study they present, which instead is a very good illustration of the kind of view of proof defended here.
Without insight accompanied with deteriorated brain functional alterations in healthy individuals with auditory verbal hallucinations: a pilot study
Authors: Zhuo Chuanjun , Ji Feng , Lin Xiaodong , Tian Hongjun , Wang Lina , Liu Sha , Sang Hong , Wang Wenqiang , Chen Chunmian 
Published: December 2019

AbstractFew studies have reported on brain functional differences between healthy individuals with auditory verbal hallucinations (Hi-AVH) with and without insight, so we designed a study to address this knowledge gap. We enrolled 12 Hi-AVH with insight, 15 Hi-AVH without insight, and 15 AVH-free controls (Healthy controls). Global functional connectivity density (gFCD) mapping was used to estimate brain networks. We found that the most common alterations in both Hi-AVH groups were increased gFCD in superior parietal lobule and superior temporal gyrus. We also found that distinct brain functional patterns of Hi-AVH without insight comprised lower gFCD in the frontal lobe oculomotor area, dorsolateral prefrontal cortex, supramarginal gyrus, primary auditory cortex, sensorimotor cortex, ventral anterior, and posterior cingulate Our pilot findings support the hypothesis that abnormal reciprocal action in the circuits for processing perception, memory, language, and attentional control may be pathological features of auditory verbal hallucinations.
Liver organoids reproduce alpha-1 antitrypsin deficiency-related liver disease
Authors: Gómez-Mariano Gema , Matamala Nerea , Martínez Selene , Justo Iago , Marcacuzco Alberto , Jimenez Carlos , Monzón Sara , Cuesta Isabel , Garfia Cristina , Martínez María Teresa , Huch Meritxell , Pérez de Castro Ignacio , Posada Manuel , Janciauskiene Sabina , Martínez-Delgado Beatriz 
Published: December 2019

Abstract
Background and aims
Alpha-1 antitrypsin (AAT) is a product of SERPINA1 gene mainly expressed by hepatocytes. Clinically relevant mutations in the SERPINA1 gene, such as Z (Glu342Lys), results in an expression of misfolded AAT protein having high propensity to polymerize, accumulate in hepatocytes and thus to enhance a risk for hepatocyte damage and subsequent liver disease. So far, the relationship between the Z-AAT accumulation and liver cell damage remains not completely understood. We present three-dimensional organoid culture systems, as a novel tool for modeling Z-AAT-related liver diseases.

Methods
We have established liver organoids from liver biopsies of patients with homozygous (ZZ) and heterozygous (MZ) deficiency and normal (MM) genotypes of AAT. The features of these organoid models were characterized by analyzing AAT protein secretion and intracellular aggregation in MZ and ZZ genotypes as well as SERPINA1 expression in differentiated cultures.

Results
Transcriptional analysis of differentiated organoid cultures by RNA-Seq showed hepatocyte-specific gene expression profile. Genes, such as ALB, APOB, CYP3A4 and SERPINA1, were validated and confirmed through quantitative-PCR analysis. The organoids from MZ and ZZ cases showed intracellular aggregation and lower secretion of AAT protein, and lower expression of ALB and APOB, as typically seen in hepatocytes from Z-AAT deficiency patients. Furthermore, organoids responded to external stimulus. Treatment with oncostatin M, a well-known inducer of SERPINA1, increased expression of the full-length transcripts (AAT-1C) as well as the short transcript of AAT (AAT-ST1C4).

Conclusions
Liver organoid model recapitulates the key features of Z-AAT deficiency and provides a useful tool for disease modeling.
Understanding ‘Successful Practice/s’ with Parents with Learning Difficulties when there are Concerns about Child Neglect: the Contribution of Social Practice Theory
Authors: Tarleton Beth , Turney Danielle 
Published: December 2019

AbstractSocial practice theory (SPT) investigates how meanings (socially available understandings/attitudes) work together with competences and materials/resources to develop shared (social) practices. SPT was used as a theoretical and analytical framework in a study which investigated ‘successful’ professional practices when working with parents with learning difficulties where there are concerns about child neglect. The research took place in three local authorities (LAs) in England that were recommended as sites of ‘successful’ practice. With the parents’ agreement, 38 professionals who worked with the eight participating families were asked about their ideas about parents with learning difficulties and neglect, their understanding of ‘successful’ practice, their experience and knowledge of working with this group of parents, how they worked with the parent and other professionals involved with the parent, as well as the resources available to them. Detailed case studies of the support provided to eight mothers were developed. It was found that the professionals shared a range of attitudes and understandings, including awareness of the many barriers faced by this disadvantaged group of parents, and that the neglect was typically linked to lack of understanding/knowledge about the child’s needs which could in many cases be mitigated through provision of support. The meanings they shared promoted an empowering, relationship-based, multi-agency approach to parents which recognised their need for support while also focusing on the needs and welfare of the children. This positive approach accords with the call for longer-term/recurrent support to be available for parents with learning difficulties alongside the development of a social model of child protection that rethinks how best to safeguard vulnerable children.
A Curriculum Design and Teaching Experience Created by and for Bioscience Postdoctoral Fellows in a Medical School
Authors: Nuebel Esther , Nowinski Sara M , Hemmis Casey W , Lindsley Janet E 
Published: December 2019

AbstractMany medical school postdoctoral fellows (postdocs) lack training in curriculum design and student-centered instruction. A team of bioscience postdocs and a medical school curriculum assistant dean co-created an experience to fill this gap. Kern’s and Kirkpatrick’s frameworks were used for the design and evaluation, respectively, of both the postdoc experience and the undergraduate course they developed. Postdocs taught the course using student-centered methods, especially team-based learning and Just-in-Time Teaching. Following a successful pilot phase, this low resource postdoc experience and undergraduate course are regularly offered. Participating postdocs develop the knowledge, skills, and attitudes to effectively participate in medical school education.
Strafford's ‘spirit’ at the royalist court: Sir George Radcliffe and Irish affairs, 1643–5
Authors: Pogson Fiona 
Published: December 2019

AbstractThis article examines how the handling of Irish affairs at the civil-war court was observed, commented upon, and probably influenced, by a man who had been at the heart of Irish government during the previous decade. It argues that the presence of Sir George Radcliffe, arguably Thomas Wentworth, earl of Strafford's closest advisor, at the royalist court in Oxford was significant in a number of respects. His surviving correspondence reveals the extent to which he was able to advise and support the newly-appointed lord lieutenant of Ireland, the marquis of Ormond. His letters also cast light on the politics of the civil-war court, in particular on how he, as an essentially second-level figure, worked flexibly with both secretaries of state. This article argues that Radcliffe's discussions with secretary of state, George Lord Digby, provided an important means by which Strafford's influence could make itself felt at the Oxford court, particularly during the 1644 negotiations with the Confederate commissioners. The pursuit of forceful, contentious policies by the former Irish administration and its contemptuous attitude towards critics, however, ensured that Radcliffe's presence at Oxford was probably unwelcome to many at court and failed to advance his career.
Reading the riot commission: Belfast, 1857
Authors: Morris R. J. 
Published: December 2019

AbstractThe year 1857 saw the first of the great riot commissions which provided much source material for Belfast history. It should be read as a continuation of the street conflict of that summer. Careful reading shows the skill with which the weak Catholic/Liberal alliance of the city managed the flow of witnesses and the naiveté of the Orange/Protestant lawyers. The Catholic/Liberal side ‘won’ the inquiry, achieving their aim of convincing the Dublin government that the local police force was ineffective if not sectarian and that Orange Order culture and evangelical street preaching was responsible for the disorder. Practical outcomes were limited. Resources were limited due to demands in other parts of Ireland and the process of taking first-class troops from Ireland to deal with the Indian mutiny. Considered in light of theories of ‘civil society’, the court was a means of countering the imperfections of representative government. Considered in the context of Ireland as a whole, events demonstrated the weakness of the Dublin authorities, their ignorance of Belfast and the importance of the resident magistrate. Much was concealed from the inquiry. The following months revealed evidence of an active Ribbon-style organisation, and the animosity of the local police and the constabulary. Attention to working class sectarianism diverted attention from elite failure to manage the class relationships of a fractured civil society.
Giving life and limb for empire: gender and occupational health in industrial Belfast, 1870–1914
Authors: Purdue Simon 
Published: December 2019

AbstractThis article explores the myriad of health hazards and dangers faced by industrial workers in Belfast between 1870 and 1914, as well as the efforts made by reformers and legislators to protect them. The article uses a variety of official sources to demonstrate the varying and distinctly gendered experience of men, women, and children working in the factories, mills, and shipyards of the city, as well as the gendered nature of the legislation put in place in this period. The article argues that the societal norms and expectations that informed legislation contributed to the gender gap that emerged in protective legislation. Female workers were seen in the same category as children and were protected paternalistically by a state still grappling with the changing position of women in an industrialising society, while men were expected to face ‘bravely’ the dangers of industrial work with little or no state intervention.