bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of adiposity on the human plasma proteome: observational and Mendelian randomisation estimates
Authors: Goudswaard Lucy J. , Bell Joshua A. , Hughes David A. , Corbin Laura J. , Walter Klaudia , Davey Smith George , Soranzo Nicole , Danesh John , Di Angelantonio Emanuele , Ouwehand Willem H. , Watkins Nicholas A. , Roberts David J. , Butterworth Adam S. , Hers Ingeborg , Timpson Nicholas J. 
Published: July 2021

Abstract
Background
Variation in adiposity is associated with cardiometabolic disease outcomes, but mechanisms leading from this exposure to disease are unclear. This study aimed to estimate effects of body mass index (BMI) on an extensive set of circulating proteins.

Methods
We used SomaLogic proteomic data from up to 2737 healthy participants from the INTERVAL study. Associations between self-reported BMI and 3622 unique plasma proteins were explored using linear regression. These were complemented by Mendelian randomisation (MR) analyses using a genetic risk score (GRS) comprised of 654 BMI-associated polymorphisms from a recent genome-wide association study (GWAS) of adult BMI. A disease enrichment analysis was performed using DAVID Bioinformatics 6.8 for proteins which were altered by BMI.

Results
Observationally, BMI was associated with 1576 proteins (P < 1.4 × 10−5), with particularly strong evidence for a positive association with leptin and fatty acid-binding protein-4 (FABP4), and a negative association with sex hormone-binding globulin (SHBG). Observational estimates were likely confounded, but the GRS for BMI did not associate with measured confounders. MR analyses provided evidence for a causal relationship between BMI and eight proteins including leptin (0.63 standard deviation (SD) per SD BMI, 95% CI 0.48–0.79, P = 1.6 × 10−15), FABP4 (0.64 SD per SD BMI, 95% CI 0.46–0.83, P = 6.7 × 10−12) and SHBG (−0.45 SD per SD BMI, 95% CI −0.65 to −0.25, P = 1.4 × 10−5). There was agreement in the magnitude of observational and MR estimates (R2 = 0.33) and evidence that proteins most strongly altered by BMI were enriched for genes involved in cardiovascular disease.

Conclusions
This study provides evidence for a broad impact of adiposity on the human proteome. Proteins strongly altered by BMI include those involved in regulating appetite, sex hormones and inflammation; such proteins are also enriched for cardiovascular disease-related genes. Altogether, results help focus attention onto new proteomic signatures of obesity-related disease.
Biological basis for novel mesothelioma therapies
Authors: Obacz Joanna , Yung Henry , Shamseddin Marie , Linnane Emily , Liu Xiewen , Azad Arsalan A. , Rassl Doris M. , Fairen-Jimenez David , Rintoul Robert C. , Nikolić Marko Z. , Marciniak Stefan J. 
Published: July 2021

AbstractMesothelioma is an aggressive cancer that is associated with exposure to asbestos. Although asbestos is banned in several countries, including the UK, an epidemic of mesothelioma is predicted to affect middle-income countries during this century owing to their heavy consumption of asbestos. The prognosis for patients with mesothelioma is poor, reflecting a failure of conventional chemotherapy that has ultimately resulted from an inadequate understanding of its biology. However, recent work has revolutionised the study of mesothelioma, identifying genetic and pathophysiological vulnerabilities, including the loss of tumour suppressors, epigenetic dysregulation and susceptibility to nutrient stress. We discuss how this knowledge, combined with advances in immunotherapy, is enabling the development of novel targeted therapies.
Preventive effect of sensorimotor exercise and resistance training on chemotherapy-induced peripheral neuropathy: a randomised-controlled trial
Authors: Müller Jana , Weiler Markus , Schneeweiss Andreas , Haag Georg Martin , Steindorf Karen , Wick Wolfgang , Wiskemann Joachim 
Published: July 2021

Abstract
Background
Chemotherapy-induced peripheral neuropathy (CIPN) is a common, unpleasant and usually long-lasting side effect of neurotoxic chemotherapeutic agents. This study aimed to investigate the preventive potential of sensorimotor- (SMT) and resistance training (RT) on CIPN.

Methods
Patients (N = 170) were randomised to SMT, RT or usual care (UC). Both exercise groups trained 3×/week for a total of 105 min/week during neurotoxic chemotherapy (mean length: 20 weeks). Before and 3 weeks after neurotoxic chemotherapy, CIPN signs/symptoms were assessed via Total Neuropathy Score (TNSr; primary endpoint) and EORTC QLQ-CIPN15 questionnaire. In addition, balance (centre of pressure), muscle strength (isokinetic), quality of life (QoL, EORTC QLQ-C30) and relative chemotherapy dose intensity (RDI) were investigated. The follow-up period covered 6 months after the end of chemotherapy.

Results
Intention-to-treat analyses (N = 159) revealed no differences regarding CIPN signs/symptoms. Exploratory per-protocol analyses (minimum training attendance rate 67%; N = 89) indicated that subjectively perceived sensory symptoms in the feet increased less during chemotherapy in the adherent exercisers (pooled group: SMT+RT) than in the UC group (−8.3 points (−16.1 to −0.4); P = 0.039, ES = 1.27). Furthermore, adherent exercisers received a higher RDI (96.6 ± 4.8 vs. 92.2 ± 9.4; P = 0.045), showed a better course of muscular strength (+20.8 Nm (11.2–30.4); P < 0.001, ES = 0.57) and QoL (+12.9 points (3.9–21.8); P = 0.005, ES = 0.64). During follow-up, CIPN signs/symptoms persisted in all groups.

Conclusions
This study demonstrates that SMT and/or RT alleviate subjectively perceived sensory CIPN symptoms in the feet and other clinically relevant cancer therapy-related outcomes, if an appropriate training stimulus is achieved.

Clinical trial registration
NCT02871284.
DCLK1 isoforms and aberrant Notch signaling in the regulation of human and murine colitis
Authors: Roy Badal C. , Ahmed Ishfaq , Stubbs Jason , Zhang Jun , Attard Thomas , Septer Seth , Welch Danny , Anant Shrikant , Sampath Venkatesh , Umar Shahid 
Published: July 2021

AbstractAlternative promoter usage generates long and short isoforms (DCLK1-L and DCLK1-S) of doublecortin-like kinase-1 (DCLK1). Tight control of Notch signaling is important to prevent and restitute inflammation in the intestine. Our aim was to investigate whether Notch1–DCLK1 axis regulates the mucosal immune responses to infection and whether this is phenocopied in human models of colitis. In the FFPE (formalin-fixed paraffin-embedded) sections prepared from the colons of ulcerative colitis (UC) and immune-mediated colitis (IRAEC) patients, expression of DCLK1 isoforms correlated positively with Notch1 and negatively with a transcriptional repressor, FoxD3 (Forkhead Box D3). DCLK1 protein staining in these sections was predominantly sub-epithelial (stromal) wherein DCLK1 co-localized with NICD, CD68, CD11c, and neutrophil elastase (NE). NE also co-stained with Citrullinated-H3 indicating the presence of neutrophil extracellular traps. In human neutrophils, elevated levels of DCLK1-S, CXCL-10, Ly6G, MPO, NE, and Notch1/2 in LPS-treated cells were inhibited when LPS was added in conjunction with Notch blocker dibenzazepine (DBZ; LPS + DBZ group). In CR-infected Rag1−/− mice, higher levels of DCLK1 in the colonic crypts were inhibited when mice received DBZ for 10 days coincident with significant dysbiosis, barrier disruption, and colitis. Concurrently, DCLK1 immunoreactivity shifted toward the stroma in CR + DBZ mice with predominance of DCLK1-S that coincided with higher Notch1 levels. Upon antibiotic treatment, partial restoration of crypt DCLK1, reduction in MPO activity, and increased survival followed. When intestinal epithelial cell-specific Dclk1-knockout (Dclk1ΔIEC) or Dclk1ΔIEC;Rag1−/− double knockout (DKO) mice were infected with CR and given a single dose of DBZ, they developed barrier defect and severe colitis with higher levels of stromal DCLK1-S, Ly6G, NE, and Notch1. We therefore propose that, by regulating the mucosal immune responses, the Notch–DCLK1 axis may be integral to the development of murine or human colitis.
MiR-146a regulates regulatory T cells to suppress heart transplant rejection in mice
Authors: Lu Jian , Wang Weiwei , Li Peiyuan , Wang Xiaodong , Gao Chao , Zhang Baotong , Du Xuezhi , Liu Yanhong , Yang Yong , Qi Feng 
Published: July 2021

AbstractRegulatory T cells (Tregs), which characteristically express forkhead box protein 3 (Foxp3), are essential for the induction of immune tolerance. Here, we investigated microRNA-146a (miR-146a), a miRNA that is widely expressed in Tregs and closely related to their homeostasis and function, with the aim of enhancing the function of Tregs by regulating miR-146a and then suppressing transplant rejection. The effect of the absence of miR-146a on Treg function in the presence or absence of rapamycin was detected in both a mouse heart transplantation model and cell co-cultures in vitro. The absence of miR-146a exerted a mild tissue-protective effect by transiently prolonging allograft survival and reducing the infiltration of CD4+and CD8+T cells into the allografts. Meanwhile, the absence of miR-146a increased Treg expansion but impaired the ability of Tregs to restrict T helper cell type 1 (Th1) responses. A miR-146a deficiency combined with interferon (IFN)-γ blockade repaired the impaired Treg function, further prolonged allograft survival, and alleviated rejection. Importantly, miR-146a regulated Tregs mainly through the IFN-γ/signal transducer and activator of transcription (STAT) 1 pathway, which is implicated in Treg function to inhibit Th1 responses. Our data suggest miR-146a controls a specific aspect of Treg function, and modulation of miR-146a may enhance Treg efficacy in alleviating heart transplant rejection in mice.
Chiral logic computing with twisted antiferromagnetic magnon modes
Authors: Jia Chenglong , Chen Min , Schäffer Alexander F. , Berakdar Jamal 
Published: July 2021

AbstractAntiferromagnetic (AFM) materials offer an exciting platform for ultrafast information handling with low cross-talks and compatibility with existing technology. Particularly interesting for low-energy cost computing is the spin wave-based realization of logic gates, which has been demonstrated experimentally for ferromagnetic waveguides. Here, we predict chiral magnonic eigenmodes with a finite intrinsic, magnonic orbital angular momentum ℓ in AFM waveguides. ℓ is an unbounded integer determined by the spatial topology of the mode. We show how these chiral modes can serve for multiplex AFM magnonic computing by demonstrating the operation of several symmetry- and topology-protected logic gates. A Dzyaloshinskii–Moriya interaction may arise at the waveguide boundaries, allowing coupling to external electric fields and resulting in a Faraday effect. The uncovered aspects highlight the potential of AFM spintronics for swift data communication and handling with high fidelity and at a low-energy cost.
Unique CO2-switched cellulose solution properties in the CO2/DBU/DMSO solvent system and the preparation of regenerated materials
Authors: Zhang Lihua , Shi Wentao , Sheng Hailiang , Feng Song , Yao Minglong , Chen Peng , Zheng Qiang , Xie Haibo 
Published: July 2021

Taking advantage of the unique CO2-switched cellulose solution properties in CO2/DBU/DMSO solvent system, the thermal-induced CO2 release provides an alternative approach to prepare regenerated cellulose materials with IVI crystalline structure.
Trichterbrust-Korrektur-OP unter Zuhilfenahme einer 3-D-Rekonstruktion des Thorax zur präoperativen Anpassung des Korrekturstabes
Authors: Scheuermann-Poley Catharina , Andreß Sebastian Martin , Willy Christian , Lieber André 
Published: July 2021

Zusammenfassung
Hintergrund Die Trichterbrust ist eine angeborene Deformität des Thoraxskeletts, bei der das Sternum und die angrenzenden Rippen trichterförmig in Richtung Wirbelsäule einsinken. Die
Pathogenese ist bisher nicht eindeutig geklärt. Es gibt verschiedene Therapieansätze, von konservativen Maßnahmen über minimalinvasive Eingriffe bis hin zur offenen Korrektur-OP. Die
betroffenen Patienten leiden unter der ästhetischen Beeinträchtigung sowie kardiopulmonalen Einschränkungen durch die Einengung des Mediastinalraumes. Die Indikationsstellung zur
Trichterbrust-Korrektur-OP unterliegt funktionellen und ästhetischen Gründen.
Patienten Wir berichten über einen 23-jährigen männlichen Patienten mit einer subjektiv beeinträchtigenden und objektiv mäßiggradigen Trichterbrust. Präoperativ wurde ein CT des
Thorax angefertigt. Der sternovertebrale Abstand betrug 8 cm, der Thoraxquerdurchmesser 28,9 cm (Haller-Index 3,6). Im präoperativen Lungenfunktionstest zeigte sich eine leichte Restriktion.
Anamnestisch beschrieb der sonst gesunde Patient Kurzatmigkeit bei stärkerer Anstrengung. Die Indikation zur Trichterbrust-Korrektur-OP wurde gestellt. Diese erfolgte in kombinierter
Operationstechnik: untere Sternotomie und Knorpelkeilresektion nach Brunner/Grob sowie Implantation eines Metallbügels ohne seitliche Antirotationsplatte. Ein zeitaufwendiger Schritt der OP
besteht in der intraoperativen Anpassung des Metallbügels. Daher fertigten wir im Vorfeld der OP anhand des Thorax-CTs eine 3-D-Rekonstruktion des knöchernen Thorax mittels 3-D-Drucker an.
Der Metallbügel wurde daran angepasst und im OP eingesetzt. Dies verkürzte die Operationsdauer um mindestens 15 min.
Ergebnisse In den postoperativen Nachuntersuchungen zeigten sich ein aufgerichteter Trichter und ein zufriedenstellendes ästhetisches Ergebnis. Sieben Monate nach Implantation
erfolgte die planmäßige Stabexplantation. Die postoperative CT-Kontrolle ergab nun einen Haller-Index von 3,25, der Lungenfunktionstest eine funktionelle Verbesserung. Subjektiv war der
Patient allzeit beschwerdefrei.
Schlussfolgerung Die Implantatanfertigung am 3-D-Modell hilft, OP-Zeit zu sparen. Die Praktikabilität ist noch nicht etabliert, da durch die Erstellung eines 3-D-Modells des
knöchernen Thorax ein anderweitig höherer Aufwand entsteht. Mit zunehmender Digitalisierung der medizinischen Welt ist es jedoch vorstellbar, dass zukünftig die Erstellung von digitalen und
realen 3-D-Modellen einfacher und kostengünstiger wird.
Neuropeptides, Inflammation, Biofilms, and diabetic Foot Ulcers
Authors: Yang Shaoling , Hu Liye , Han Rui , Yang Yiwen 
Published: July 2021

AbstractA diabetic foot ulcer (DFU) is a serious complication in patients with diabetes mellitus (DM). A DFU is the most common cause of non-traumatic limb amputation, and patients with DFUs have increased mortality rates within 5 years after amputation. DFUs also increase the risk of cardiovascular and cerebrovascular diseases; therefore, with the increasing incidence and prevalence of diabetic foot wounds, DFUs are gradually becoming a major public health problem. The pathophysiology of DFUs is complicated and remains unclear. In recent years, many studies have demonstrated that the pathophysiology of DFUs is especially associated with neuropeptides, inflammation, and biofilms. Neuropeptides, especially substance P (SP) and calcitonin gene-related peptide (CGRP), play an important role in wound healing. SP and CGRP accelerate the healing of cutaneous wounds by promoting neovascularization, inhibiting the release of certain proinflammatory chemokines, regulating macrophage polarization, and so on. However, the expression of SP and CGRP was downregulated in DM and DFUs. DFUs are characterized by a sustained inflammatory phase. Immune cells such as neutrophils and macrophages are involved in the sustained inflammatory phase in DFUs by extracellular traps (NETs) and dysregulated macrophage polarization, which delays wound healing. Furthermore, DFUs are at increased risk of biofilm formation. Biofilms disturb wound healing by inducing a chronic inflammatory response, inhibiting macrophage phagocytosis and keratinocyte proliferation migration, and transferring antimicrobial resistance genes. To understand the relationships among neuropeptides, inflammation, biofilms, and DFUs, this review highlights the recent scientific advances that provide possible pathophysiological insights into the delayed healing of DFUs.
Poorly Understood Pelvic Venous Disorders Require a Multidisciplinary Approach
Authors: Doganci Suat 
Published: July 2021

AbstractPelvic venous diseases encompasses all chronic pathologies of pelvic veins caused by venous hypertension and retrograde flow in pelvic veins. It is commonly unexplained and often underdiagnosed cause of chronic pelvic pain in women of productive age. Pelvic venous pathologies are a part of multidisciplinary problem that should be considered in a holistic approach. Newly offered SVP classification may help correctly classifying patients and using the same nomenclature. Endovascular treatment options are highly effective with good long-term results. Patients with inconclusive gynecologists examinations should be referred to a specialist for the investigation of pelvic venous disorders.
Advances in the Semi-Synthesis of Triterpenoids
Authors: Liao Jin-Xi , Sun Jian-Song , Hu Zhen-Ni , Liu Hui 
Published: July 2021

AbstractRecent achievements in triterpenoid semi-synthesis are discussed in this short review, which is divided into three parts according to the type of synthetic strategy being employed. These strategies include functionalization, modification of the carbon skeleton, and glycosylation. In the section on functionalization strategies, both functional group interconversions and new functional group installations on triterpenoid starting materials are described. The section on modification of the carbon skeleton is divided into three parts according to the tactic being applied, and incorporates rearrangement of the carbon skeleton, ring scission, and introduction of an additional heterocyclic ring. Meanwhile, in the section on glycosylation, notable achievements in the semi-synthesis of both natural and artificial triterpene saponins are discussed. Overall, the pivotal transformations that have brought about striking chemical structure variations of triterpenoid starting materials are highlighted herein, and it is hoped that this short review will provide inspiration to both established and new investigators engaged in this field of research. 1	Introduction2	Semi-Synthesis of Triterpenoids via Functionalization Strategies2.1	Functionalization of Rings with Functional Groups2.2	Functionalization of a Side Chain2.3	Functionalization of Rings without Existing Functional Groups 2.4	Functionalization of Angular Methyl Groups2.5	Functionalization of Angular Methyl Groups and Functional-Group-Free Rings2.6	Multisite Modifications3	Semi-Synthesis of Triterpenoids via C-Skeleton Modification Strategies3.1	Rearrangement Tactics3.2	Ring-Opening Tactics3.3	Additional Ring Introduction Tactics4	emi-Synthesis of Triterpenoids via a Glycosylation Strategy5	Conclusions and Outlook
Factor momentum, option-implied volatility scaling, and investor sentiment
Authors: Grobys Klaus , Kolari James W. , Rutanen Jere 
Published: July 2021

AbstractFactor momentum produces robust average returns that exhibit a similar economic magnitude as stock price momentum. To the extent that the post-earnings announcement drift (PEAD) factor captures mispricing, winner factors earn profits from being long on underpriced stocks and short on overpriced stocks. Conversely, loser-factors’ negative exposure to the PEAD factor suggests that loser factors capture mispricing by being long on overpriced stocks and short on underpriced stocks. Option-implied volatility scaling increases both the economic magnitude and statistical significance of factor momentum. Factor momentum is not exposed to the same crashes as stock price momentum and therefore could provide a hedge for stock price momentum crash risks. Also, factor momentum mispricing is more pronounced when investor sentiment is high.
A system of circumstantial evidence for fact-finding in criminal trial
Authors: Ri Yong-Sok , Kwon Yong-Min , Pang Wi-Song 
Published: July 2021

Abstract
One of the most intractable, but significant problems in the theory of legal evidence concerns circumstantial
evidence. The diversity and complexity of criminal cases cause some bottlenecks and difficulties in developing reasonable methods
to prove the criminal issue by means of circumstantial evidence. The main purpose of this paper is to present more effective
methods of fact-finding just by means of a system of circumstantial evidence (SCE). On the basis of analysis of the nature of
circumstantial evidence, we find it necessary for the prosecution to construct a SCE in order to make a judge or jury accept the
prosecution’s conclusion as the best explanation. We also present a reasonable logical structure of such a system and address some
legal and logical problems in introducing it.
Lingue, dialetti e religione nelle aree occitane e francoprovenzali
Authors: Rivoira Matteo 
Published: July 2021

AstrattaGli stretti e complessi rapporti tra religione e lingua sono ormai uno degli ambiti di studio della sociologia del linguaggio. L’adozione in ambito religioso di determinati codici discende in genere dalla disponibilità di varietà elaborate nel repertorio linguistico comunitario, ma al contempo essa può determinare ristrutturazioni del repertorio stesso,in primissullo status delle lingue implicate. Lingua e religione, inoltre, possono essere individuate come forti simboli di appartenenza a una storia e a un’identità culturale. Nel presente lavoro saranno tratteggiati gli aspetti storici e macro-sociolinguistici che caratterizzano l’area galloromanza italiana (Valle d’Aosta e Piemonte occidentale). Ne verranno in particolare presentate le strutture repertoriali e discusso il ruolo del francese e delle altre varietà locali nel contesto religioso, caratterizzato dalla presenza storica di due diverse confessioni cristiane (cattolica e evangelica valdese). Infine saranno discusse le scelte linguistiche e religiose operate nei diversi contesti, in una prospettiva tesa ad evidenziare le implicazioni identitarie.
La romaní in Italia tra rappresentazione e legittimazione
Authors: Scala Andrea 
Published: July 2021

Astratta
L’articolo esamina le dinamiche connesse con la (auto-)rappresentazione e la legittimazione della romaní in Italia. Comunità di lingua romaní sono presenti in Italia fin dalla prima età moderna e tutti i parlanti di romaní di antico insediamento nella penisola sono cittadini italiani, tuttavia la legge 482/1999 della Repubblica Italiana "Norme in materia di tutela delle minoranze linguistiche storiche" non include la romaní tra le lingue di minoranza da tutelare. L’esclusione della romaní dalla legge trova la sua radice prima in un’errata rappresentazione dei suoi locutori, generalmente percepiti come nomadi, mentre non lo sono più da tempo. La legge 482/1999 di fatto tutela le minoranze linguistiche legate a un territorio e la falsa, ma diffusa, percezione dei parlanti romaní come nomadi ha offerto un comodo pretesto a chi voleva escludere dalla tutela la lingua dei rom e dei sinti italiani. Il panorama linguistico della romaní in Italia risulta assai complesso e l’articolo si sforza di descriverlo e spiegarlo in diversi aspetti. I gruppi rom e sinti stanziati in Italia parlano dialetti piuttosto diversi, hanno repertori linguistici differenti, non percepiscono di essere accomunati da un’unica origine etnico-linguistica e non hanno gli stessi atteggiamenti nei confronti dell’uso pubblico della romaní. Questi fattori, insieme alla rappresentazione distorta delle comunità rom e sinte presso la cultura maggioritaria, rendono assai complessa la progettazione di un percorso di tutela. Tuttavia il riconoscimento della romaní come lingua di minoranza in Italia rimane un obbiettivo di alto valore civile, che si potrà forse perseguire con leggi regionali mirate.