bluuebunny/crossref_metadata_2025_split huggingface dataset:
Progress in cardiac research: from rebooting cardiac regeneration to a complete cell atlas of the heart
Authors: Davidson Sean M , Padró Teresa , Bollini Sveva , Vilahur Gemma , Duncker Dirk J , Evans Paul C , Guzik Tomasz , Hoefer Imo E , Waltenberger Johannes , Wojta Johann , Weber Christian 
Published: June 2021

AbstractWe review some of the important discoveries and advances made in basic and translational cardiac research in 2020. For example, in the field of myocardial infarction (MI), new aspects of autophagy and the importance of eosinophils were described. Novel approaches, such as a glycocalyx mimetic, were used to improve cardiac recovery following MI. The strategy of 3D bio-printing was shown to allow the fabrication of a chambered cardiac organoid. The benefit of combining tissue engineering with paracrine therapy to heal injured myocardium is discussed. We highlight the importance of cell-to-cell communication, in particular, the relevance of extracellular vesicles, such as exosomes, which transport proteins, lipids, non-coding RNAs, and mRNAs and actively contribute to angiogenesis and myocardial regeneration. In this rapidly growing field, new strategies were developed to stimulate the release of reparative exosomes in ischaemic myocardium. Single-cell sequencing technology is causing a revolution in the study of transcriptional expression at cellular resolution, revealing unanticipated heterogeneity within cardiomyocytes, pericytes and fibroblasts, and revealing a unique subpopulation of cardiac fibroblasts. Several studies demonstrated that exosome- and non-coding RNA-mediated approaches can enhance human induced pluripotent stem cell (iPSC) viability and differentiation into mature cardiomyocytes. Important details of the mitochondrial Ca2+ uniporter and its relevance were elucidated. Novel aspects of cancer therapeutic-induced cardiotoxicity were described, such as the novel circular RNA circITCH, which may lead to novel treatments. Finally, we provide some insights into the effects of SARS-CoV-2 on the heart.
Identification of sur2 mutation affecting the lifespan of fission yeast
Authors: Kurauchi Tatsuhiro , Matsui Kotaro , Shimasaki Takafumi , Ohtsuka Hokuto , Tsubouchi Satoshi , Ihara Kunio , Tani Motohiro , Aiba Hirofumi 
Published: June 2021

ABSTRACT
Yeast is a suitable model system to analyze the mechanism of lifespan. In this study, to identify novel factors involved in chronological lifespan, we isolated a mutant with a long chronological lifespan and found a missense mutation in the sur2+ gene, which encodes a homolog of Saccharomyces cerevisiae sphingolipid C4-hydroxylase in fission yeast. Characterization of the mutant revealed that loss of sur2 function resulted in an extended chronological lifespan. The effect of caloric restriction, a well-known signal for extending lifespan, is thought to be dependent on the sur2+ gene.
Rayleigh-wave H/V ratio measurement from ambient noise cross-correlations and its sensitivity to VP: a numerical study
Authors: Malkoti Ajay , Datta Arjun , Hanasoge Shravan M 
Published: June 2021

SUMMARY
The promise of passive seismology has increasingly been realized in recent years. Given the expense in installing and maintaining seismic station networks, it is important to extract as much information from the measurements as possible. In this context, the ellipticity or H/V amplitude ratio of Rayleigh waves can prove to be a valuable observable in ambient noise seismology due to its complimentary sensitivity to subsurface structure, compared to phase and group-velocity dispersion, as well as its potential for constraining VP structure in addition to VS. However, the suitability of the Rayleigh H/V ratio in noise-based studies depends on the accurate interpretation of measurements made on multicomponent ambient-noise cross-correlations. We present a synthetic study that critically examines measurements commonly interpreted as the Rayleigh-wave H/V ratio, under realistic scenarios of spatially distributed and non-uniform noise sources. Using the surface wave terms of Green’s function in a laterally homogeneous medium, we rigorously model multicomponent cross-correlations for arbitrary noise-source distributions and extract from them standard estimates of the H/V ratio. Variation of these measurements as a function of VP is studied empirically, by brute-force simulation. We find that the measurements depart significantly from the theoretical Rayleigh-wave H/V for the medium in question, when noise sources are strongly directional or anisotropic. Love waves, if present in the cross-correlations, also have the potential to significantly bias interpretation. Accurate interpretation of the H/V ratio measurement thus rests on carefully modelling these effects. However, the sensitivity to VP structure is comparable to that of the classic Rayleigh-wave H/V. We also propose a new measurement for cross-correlations that has slightly greater sensitivity to VP. Finally, uncertainty analysis on synthetic tests suggests that simplistic interpretations of Rayleigh-wave ellipticity are only effective (in resolving VP structure) when the Love-wave contamination is negligible and measurement uncertainties are less than 10 per cent.
Serum Analyte Profiles Associated With Crohn’s Disease and Disease Location
Authors: Boucher Gabrielle , Paradis Alexandre , Chabot-Roy Geneviève , Coderre Lise , Hillhouse Erin E , Bitton Alain , Des Rosiers Christine , Levings Megan K , Schumm L Philip , Lazarev Mark , Brant Steve R , Duerr Richard , McGovern Dermot , Silverberg Mark S , Cho Judy , Lesage Sylvie , Rioux John D ,   iGenoMed Consortium, Bitton Alain , Boucher Gabrielle , Charron Guy , Des Rosiers Christine , Forest Anik , Goyette Philippe , Ivinson Sabine , Joseph Lawrence , Kohen Rita , Lachaine Jean , Lesage Sylvie , Levings Megan , Rioux John D , Thompson-Legault Julie , Vachon Luc , Veilleux Sophie , White-Guay Brian ,   NIDDK IBD Genetics Consortium, Bajpai Manisha , Birch Sondra , Bitton Alain , Borowski Krzysztof , Botwin Gregory , Boucher Gabrielle , Brant Steven R , Chen Wei , Cho Judy H , Cordero Roberto , Côté-Daigneault Justin , Daly Mark J , Datta Lisa , Duerr Richard H , Filice Melissa , Fleshner Philip , Gettler Kyle , Giri Mamta , Goyette Philippe , Hao Ke , Haritunians Talin , Itan Yuval , Johnston Elyse , Konnikova Liza , Landers Carol , Lazarev Mark , Li Dalin , McGovern Dermot P B , Mengesha Emebet , Merad Miriam , Miladinova Vessela , Nayeri Shadi , Proksell Siobhan , Raquel Milgrom , Rioux John D , Rymaszewski Klaudia , Sabic Ksenija , Sands Bruce , Schumm L Philip , Schwartz Marc B , Silverberg Mark S , Simpson Claire L , Stempak Joanne M , Stevens Christine , Targan Stephan R , Xavier Ramnik 
Published: June 2021

Abstract

Background
Crohn’s disease (CD) can affect any segment of the digestive tract but is most often localized in the ileal, ileocolonic, and colorectal regions of the intestines. It is believed that the chronic inflammation in CD is a result of an imbalance between the epithelial barrier, the immune system, and the intestinal microbiota. The aim of the study was to identify circulating markers associated with CD and/or disease location in CD patients.

Methods
We tested 49 cytokines, chemokines, and growth factors in serum samples from 300 patients with CD and 300 controls. After quality control, analyte levels were tested for association with CD and disease location.

Results
We identified 13 analytes that were higher in CD patients relative to healthy controls and that remained significant after conservative Bonferroni correction (P &lt; 0.0015). In particular, CXCL9, CXCL1, and interleukin IL-6 had the greatest effect and were highly significant (P &lt; 5 × 10–7). We also identified 9 analytes that were associated with disease location, with VEGF, IL-12p70, and IL-6 being elevated in patients with colorectal disease (P &lt; 3 × 10–4).

Conclusions
Multiple serum analytes are elevated in CD. These implicate the involvement of multiple cell types from the immune, epithelial, and endothelial systems, suggesting that circulating analytes reflect the inflammatory processes that are ongoing within the gut. Moreover, the identification of distinct profiles according to disease location supports the existence of a biological difference between ileal and colonic CD, consistent with previous genetic and clinical observations.
Factors associated with the intention of community pharmacists to report adverse drug reactions to regulatory authority in Malaysia: application of the theory of planned behaviour
Authors: Raghvan Hari Pretha Nair , Fatokun Omotayo 
Published: June 2021

Abstract

Objectives
It is known that community pharmacists in Malaysia underreport adverse drug reactions (ADRs). In order to improve ADR reporting, a theory-based understanding of the factors associated with the community pharmacists’ reporting behaviour is important. This study used the theory of planned behaviour (TPB) to identify the predictors of behavioural intention to report ADRs to the regulatory authority among community pharmacists in Malaysia and to assess the relative importance of the predictors.

Methods
A questionnaire-based study was conducted among 188 randomly selected community pharmacists in the state of Johor, Malaysia. The questionnaire included four main TPB constructs (intention, attitude, subjective norms and perceived behavioural control) and related measures, including perceived moral obligation, past reporting behaviour and sociodemographic variables. Descriptive and hierarchical regression analyses were conducted.

Key findings
A total of 164 questionnaires were collected. The mean score of intention to report ADRs was 15.43 (SD = 2.99). The final model of the hierarchical regression analysis showed that attitude towards ADR reporting (P = 0.004), subjective norm (P = 0.010) and perceived moral obligation (P = 0.014) were significant predictors of intention to report ADRs. Attitude was the most significant predictor, followed by subjective norm and perceived moral obligation.

Conclusions
Interventions targeting community pharmacists’ attitude, subjective norms and perceived moral obligations towards ADR reporting, with a specific focus on attitude would likely have a positive impact on improving ADR reporting in Malaysia.
Strong uniform consistency with rates for kernel density estimators with general kernels on manifolds
Authors: Wu Hau-Tieng , Wu Nan 
Published: June 2021

Abstract
When analyzing modern machine learning algorithms, we may need to handle kernel density estimation (KDE) with intricate kernels that are not designed by the user and might even be irregular and asymmetric. To handle this emerging challenge, we provide a strong uniform consistency result with the $L^\infty $ convergence rate for KDE on Riemannian manifolds with Riemann integrable kernels (in the ambient Euclidean space). We also provide an $L^1$ consistency result for kernel density estimation on Riemannian manifolds with Lebesgue integrable kernels. The isotropic kernels considered in this paper are different from the kernels in the Vapnik–Chervonenkis class that are frequently considered in statistics society. We illustrate the difference when we apply them to estimate the probability density function. Moreover, we elaborate the delicate difference when the kernel is designed on the intrinsic manifold and on the ambient Euclidian space, both might be encountered in practice. At last, we prove the necessary and sufficient condition for an isotropic kernel to be Riemann integrable on a submanifold in the Euclidean space.
α2-3 Sialic acid binding and uptake by human monocyte-derived dendritic cells alters metabolism and cytokine release and initiates tolerizing T cell programming
Authors: Lübbers Joyce , Eveline Li Rui-Jún , Gorki Friederike S , Bruijns Sven C M , Gallagher Ashley , Kalay Hakan , Ambrosini Martino , Molenaar Douwe , Van den Bossche Jan , van Vliet Sandra J , van Kooyk Yvette 
Published: June 2021

Summary
Dendritic cells (DCs) are key in the initiation of the adaptive T cell responses to tailor adequate immunity that corresponds to the type of pathogen encountered. Oppositely, DCs control the resolution phase of inflammation and are able to induce tolerance after receiving anti-inflammatory cytokines or upon encounter of self-associated molecular patterns, such as α2-3 linked sialic acid (α2-3sia).
Objective: We here investigated whether α2-3sia, that bind immune inhibitory Siglec receptors, would alter signaling and reprogramming of LPS-stimulated human monocyte-derived DCs (moDCs).
Methods and Results: Transcriptomic analysis of moDCs stimulated with α2-3sia-conjugated dendrimers revealed differentially expressed genes related to metabolic pathways, cytokines, and T cell differentiation. An increase in genes involved in ATPase regulator activity, oxidoreductase activity, and glycogen metabolic processes was detected. Metabolic extracellular flux analysis confirmed a more energetic moDC phenotype upon α2-3sia binding as evidenced by an increase in both glycolysis and mitochondrial oxidative phosphorylation. TH1 differentiation promoting genes IFNL and IL27, were significantly downregulated in the presence of α2-3sia. Functional assays confirmed that α2-3sia binding to moDCs induced phosphorylation of Siglec-9, reduced production of inflammatory cytokines IL-12 and IL-6, and increased IL-10. Surprisingly, α2-3sia-differentiated moDCs promoted FoxP3+CD25+/-CD127- regulatory T cell differentiation and decreased FoxP3-CD25-CD127- effector T cell proliferation.
Conclusions: In conclusion, we demonstrate that α2-3sia binding to moDCs, phosphorylates Siglec-9, alters metabolic pathways, cytokine signaling, and T cell differentiation processes in moDCs and promotes regulatory T cells. The sialic acid-Siglec axis on DCs is therefore, a novel target to induce tolerance and to explore for immunotherapeutic interventions aimed to restore inflammatory processes.
Multiplicative and Linear Dependence in Finite Fields and on Elliptic Curves Modulo Primes
Authors: Barroero Fabrizio , Capuano Laura , Mérai László , Ostafe Alina , Sha Min 
Published: June 2021

AbstractFor positive integers $K$ and $L$, we introduce and study the notion of $K$-multiplicative dependence over the algebraic closure ${\overline{{\mathbb{F}}}}_p$ of a finite prime field ${\mathbb{F}}_p$, as well as $L$-linear dependence of points on elliptic curves in reduction modulo primes. One of our main results shows that, given non-zero rational functions $\varphi _1,\ldots ,\varphi _m, \varrho _1,\ldots ,\varrho _n\in{\mathbb{Q}}(X)$ and an elliptic curve $E$ defined over the rational numbers ${\mathbb{Q}}$, for any sufficiently large prime $p$, for all but finitely many $\alpha \in{\overline{{\mathbb{F}}}}_p$, at most one of the following two can happen: $\varphi _1(\alpha ),\ldots ,\varphi _m(\alpha )$ are $K$-multiplicatively dependent or the points $(\varrho _1(\alpha ),\cdot ), \ldots ,(\varrho _n(\alpha ),\cdot )$ are $L$-linearly dependent on the reduction of $E$ modulo $p$. As one of our main tools, we prove a general statement about the intersection of an irreducible curve in the split semiabelian variety ${\mathbb{G}}_{\textrm{m}}^m \times E^n$ with the algebraic subgroups of codimension at least $2$.As an application of our results, we improve a result of M. C. Chang and extend a result of J. F. Voloch about elements of large order in finite fields in some special cases.
The German Federal Constitutional Court Ruling and the European Central Bank’s Strategy
Authors: Feld Lars P , Wieland Volker 
Published: June 2021

ABSTRACT
The ruling of the German Federal Constitutional Court and its call for conducting and communicating proportionality assessments regarding monetary policy have been the subject of some controversy. However, it can also be understood as a way to strengthen the de facto independence of the European Central Bank (ECB). This article shows how a regular proportionality check could be integrated in the ECB’s strategy, which is currently undergoing a systematic review. In particular, it proposes that quantitative benchmarks for policy rates and the central bank balance sheet should be included. Deviations from such benchmarks can have benefits in terms of the intended path for inflation while involving costs in terms of risks and side effects that need to be balanced. Practical applications to the euro area are provided.
Treatment outcomes of erlotinib plus gemcitabine as late-line chemotherapy in unresectable pancreatic cancer
Authors: Mie Takafumi , Sasaki Takashi , Takeda Tsuyoshi , Okamoto Takeshi , Mori Chinatsu , Furukawa Takaaki , Yamada Yuto , Kasuga Akiyoshi , Matsuyama Masato , Ozaka Masato , Sasahira Naoki 
Published: June 2021

Abstract

Objective
With the introduction of modified FOLFIRINOX and gemcitabine plus nab-paclitaxel therapy for unresectable pancreatic cancer, erlotinib plus gemcitabine therapy is now occasionally used as late-line therapy. This study investigates outcomes of treatment with erlotinib plus gemcitabine for unresectable pancreatic cancer.

Methods
We retrospectively analysed consecutive patients with unresectable pancreatic cancer treated with erlotinib plus gemcitabine as the third or later-line chemotherapy between March 2014 and December 2020 in our hospital.

Results
A total of 56 patients were included (third line/fourth or later line = 42/14). All patients were previously treated with gemcitabine plus nab-paclitaxel and 45 patients were previously treated with modified FOLFIRINOX. The median progression-free survival (PFS) and overall survival (OS) were 1.6 and 4.6 months, respectively. The disease control rate was 21.4%. Performance status, modified Glasgow prognostic score and carcinoembryonic antigen level were independently associated with survival. Our prognostic model using these parameters could classify patients into good (n = 32) and poor (n = 24) prognostic groups. The median PFS and OS were longer in good than in poor prognostic group, but the difference in PFS was very small (PFS: 2.1 vs. 1.4 months, P = 0.01. OS: 6.8 vs. 2.4 months, P &lt; 0.01). Interstitial pneumonia occurred in one patient (1.8%).

Conclusions
Benefits of erlotinib plus gemcitabine as late-line chemotherapy were limited, particularly with respect to PFS. Development of more effective third-line treatment options is desirable in the future.
The role of soil-borne fungi in driving the coexistence ofPinus massonianaandLithocarpus glaberin a subtropical forest via plant–soil feedback
Authors: Pan Yumei , Yao Zhongyuan , Zhang Naili , Veen G F 
Published: June 2021

AbstractAimsPlant–soil feedback (PSF) is a key mechanism that can facilitate tree species coexistence and diversity. Substantial evidence suggests that species-specific soil-borne pathogens around adult trees limit the performance of home (conspecific) seedlings relative to foreign (heterospecific) seedlings. However, the underlying mechanism remains largely elusive.MethodsHere, we conducted a reciprocal transplant pot experiment using seedlings and from two tree species, Pinus massoniana and Lithocarpus glaber that are dominant and coexist in a subtropical, evergreen, broad-leaf forest in Gutianshan, Zhejiang Province of eastern China. We examined how seedlings from the two tree species responded to soils originating from underneath their own versus the other tree species, using a full-factorial design. Additionally, we added a fungicide (benomyl) to half of the pots to evaluate the role of soil-borne fungi on seedling growth.Important FindingsWe found that the seedlings from L. glaber grew better in soils that were collected from beneath the canopy of P. massoniana, while seedling growth of P. massioniana was not affected by soil origin. The addition of fungicide benomyl resulted in a shift towards more positive PSF effects for L. glaber, indicating that L. glaber seedlings performed better in their own soils than in soils from P. massoniana in the absence of fungi. Our findings highlight the importance of soil-borne pathogenic and ectomycorrhizal fungi in driving PSF, and indicate that PSF may promote the coexistence of two subtropical tree species by reducing the performance of L. glaber in own soils.
Infarcted wandering spleen: A case report from Saudi Arabia
Authors: Alghamdi Raid , Alzahrnai Amer , Alosaimi Abdulaziz , Albabtain Ibrahim 
Published: June 2021

Abstract
Spleen is normally positioned in the left upper quadrant. Abnormal location where it is not found in its normal anatomical position is called wandering spleen (WS). Wandering spleen is a rare medical condition that occurs due to developmental abnormality or acquired laxity of the ligaments that hold the spleen in its normal anatomical position. It affects children and young adults, especially childbearing age women. Patients affected with this condition may present with nonspecific symptoms requiring a high index of suspicion. Here, we are presenting a 20-year-old female known to have WS ended up with infarcted WS requiring emergency splenectomy.
The Sw-5b NLR nucleotide-binding domain plays a role in oligomerization, and its self-association is important for activation of cell death signaling
Authors: Zhao Xiaohui , Chen Zhengqiang , Wu Qian , Cai Yazhen , Zhang Yu , Zhao Ruizhen , Yan Jiaoling , Qian Xin , Li Jia , Zhu Min , Hong Lizhou , Xing Jincheng , Khan Nasr Ullah , Ji Yinghua , Wu Peijun , Huang Changjun , Ding Xin Shun , Zhang Hui , Tao Xiaorong 
Published: June 2021

Abstract
Plant and animal intracellular nucleotide-binding and leucine-rich repeat (NLR) receptors play important roles in sensing pathogens and activating defense signaling. However, the molecular mechanisms underlying the activation of host defense signaling by NLR proteins remain largely unknown. Many studies have determined that the coil–coil (CC) or Toll and interleukin-1 receptor/resistance protein (TIR) domain of NLR proteins and their dimerization/oligomerization are critical for activating downstream defense signaling. In this study, we demonstrated that, in tomato, the nucleotide-binding (NB) domain Sw-5b NLR alone can activate downstream defense signaling, leading to elicitor-independent cell death. Sw-5b NB domains can self-associate, and this self-association is crucial for activating cell death signaling. The self-association was strongly compromised after the introduction of a K568R mutation into the P-loop of the NB domain. Consequently, the NBK568R mutant induced cell death very weakly. The NBCΔ20 mutant lacking the C-terminal 20 amino acids can self-associate but cannot activate cell death signaling. The NBCΔ20 mutant also interfered with wild-type NB domain self-association, leading to compromised cell death induction. By contrast, the NBK568R mutant did not interfere with wild-type NB domain self-association and its ability to induce cell death. Structural modeling of Sw-5b suggests that NB domains associate with one another and likely participate in oligomerization. As Sw-5b-triggered cell death is dependent on helper NLR proteins, we propose that the Sw-5b NB domain acts as a nucleation point for the assembly of an oligomeric resistosome, probably by recruiting downstream helper partners, to trigger defense signaling.