bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gravitationally collapsing stars in f(R) gravity
Authors: Jaryal Suresh C. , Chatterjee Ayan 
Published: April 2021

AbstractThe gravitational dynamics of a collapsing matter configuration which is simultaneously radiating heat flux is studied in f(R) gravity. Three particular functional forms in f(R) gravity are considered to show that it is possible to envisage boundary conditions such that the end state of the collapse has a weak singularity and that the matter configuration radiates away all of its mass before collapsing to reach the central singularity.
Functional Analysis of DNMT1 SNPs (rs2228611 and rs2114724) Associated with Schizophrenia
Authors: Saxena Sonal , Maroju Pranay Amruth , Choudhury Sumana , Voina Vidhya Chitta , Naik Poonam , Gowdhaman Kavitha , Kkani Poornima , Chennoju Kiranmai , Ganesh Kumar S. , Ramasubramanian C. , Prasad Rao G. , Jamma Trinath , Narayan Kumar Pranav , Mohan K. Naga 
Published: April 2021

A recent study showed the association of minor alleles of rs2228611 (T allele) and rs2114724 (T allele) of DNMT1 with schizophrenia (SZ) and suggested their effects on splicing of the transcripts. We performed a replication study using 310 controls and 304 SZ patients and confirmed the association of the homozygous minor allele genotypes with SZ (

P

= 0.04 for rs2114724 and

P

= 0.007 for rs2228611). This significant association persisted after Bonferroni correction when the previously published data of 301 controls and 325 patients were also considered (

P

≤ 0.0002). In addition, we found that the proportion of male patients with homozygous minor alleles at rs2114724 was significantly higher than that of females (

P

= 0.002). When haplotype analysis of both loci was performed, we observed a significant association of T/T–T/T and T/T–C/T (

P

= 0.04) haplotypes with SZ. To gain insights into the functional effects of the two SNPs on the levels of DNMT1 transcripts, quantitative real-time PCR experiments were performed using peripheral blood monocytes from 10 individuals each with T/T–T/T (homozygous minor allele), C/T–C/T (heterozygous), and C/C–C/C (homozygous major allele) haplotypes. Independently, the levels of DNMT1 protein were also compared in three individuals each by immunofluorescence. These results suggest that neither DNMT1 transcript nor the protein levels were significantly different in the peripheral blood monocytes among the individuals studied for the three groups. Taken together, our results confirm that the two minor alleles in homozygosity are associated with SZ but with no discernible effects on transcript or protein levels of DNMT1 in the peripheral blood monocytes of the small number of samples tested.
The Complex Integration of T-cell Metabolism and Immunotherapy
Authors: Madden Matthew Z. , Rathmell Jeffrey C. 
Published: April 2021

Abstract

Immune oncology approaches of adoptive cell therapy and immune checkpoint blockade aim to activate T cells to eliminate tumors. Normal stimulation of resting T cells induces metabolic reprogramming from catabolic and oxidative metabolism to aerobic glycolysis in effector T cells, and back to oxidative metabolism in long-lived memory cells. These metabolic reprogramming events are now appreciated to be essential aspects of T-cell function and fate. Here, we review these transitions, how they are disrupted by T-cell interactions with tumors and the tumor microenvironment, and how they can inform immune oncology to enhance T-cell function against tumors.

Significance:
T-cell metabolism plays a central role in T-cell fate yet is altered in cancer in ways that can suppress antitumor immunity. Here, we discuss challenges and opportunities to stimulate effector T-cell metabolism and improve cancer immunotherapy.
Gut Microbiota and Antitumor Immunity: Potential Mechanisms for Clinical Effect
Authors: Baruch Erez N. , Wang Jingjing , Wargo Jennifer A. 
Published: April 2021

AbstractSeveral landmark preclinical studies have shown an association between the gut microbiota and the effectiveness of immunotherapy for cancer. These studies have sparked clinical trials aimed at modulating the gut microbiota in order to improve clinical response rates to immunotherapy. Despite this, the mechanisms through which the gut microbiota influences the effectiveness of immunotherapy are still incompletely characterized. Preclinical and preliminary clinical findings from numerous types of gut microbiota modulation studies, including fecal transplantation, probiotics, consortia, and diet, demonstrate that favorable microbiota modulation is associated with increased intratumoral infiltration of CD8+ effector T cells. This CD8+ T-cell infiltration is often associated with enhanced intratumoral activity of T-helper type 1 cells and dendritic cells and a lower density of immunosuppressive cells. Herein, we discuss how gut microbiota may affect the activity of immune cells by at least three interlacing mechanisms: activation of pattern recognition receptors, molecular mimicry, and impact of metabolites. We also discuss the therapeutic potential and limitations of the different gut microbiota modulation techniques and their putative mechanisms of immune activation.
HSP25 Vaccination Attenuates Atherogenesis via Upregulation of LDLR Expression, Lowering of PCSK9 Levels and Curbing of Inflammation
Authors: Chen Yong-Xiang , Shi Chunhua , Deng Jingti , Diao Catherine , Maarouf Nadia , Rosin Matthew , Shrivastava Vipul , Hu Angie A. , Bharadwa Sonya , Adijiang Ayinuer , Ulke-Lemee Annegret , Gwilym Brenig , Hellmich Alexandria , Malozzi Christopher , Batulan Zarah , Dean Jonathan L.E. , Ramirez F. Daniel , Liu Jingwen , Gerthoffer William T. , O’Brien Edward R. 
Published: April 2021

Objective:

Elevated HSP27 (heat shock protein 27) levels predict relative freedom from cardiovascular events. Over-expression or twice daily subcutaneous injections of human HSP27 in
ApoE
−/−
mice reduces blood and plaque cholesterol levels, as well as inflammation and atherosclerotic plaque burden. Antibodies to HSP27 are present in human blood, and the purpose of the current studies is to explore their role.

Approach and Results:

Blood levels of both HSP27 and anti-HSP27 IgG antibodies are elevated in healthy controls compared with patients with cardiovascular disease.
ApoE
−/−
mice fed a high-fat diet and vaccinated with recombinant HSP25 (rHSP25, murine ortholog) show increased levels of anti-HSP25 IgG antibodies and reductions in plasma cholesterol and atherogenesis. Moreover, rHSP25 vaccination markedly lowered serum amyloid A levels as well as hepatic macrophage abundance and inflammatory cytokine expression. The effects of the HPS25 vaccination on cholesterol metabolism are divergent: increased hepatic LDLR (low-density lipoprotein receptor) mRNA and protein expression and reduced plasma PCSK9 (proprotein convertase subtilisin/kexin type 9) levels—despite no effect on PCSK9 expression. In vitro, the HSP27 immune complex upregulates hepatocyte LDLR mRNA and protein expression independent of intracellular cholesterol levels and increases LDLR promoter activity. The increase in LDLR expression by the HSP27 immune complex is dependent upon activation of the NF-κB (nuclear factor κ light chain enhancer of activated B cells) pathway. Hepatocyte PCSK9 protein levels are reduced after HSP27 immune complex treatment in vitro despite only minor transient effects on gene expression.

Conclusions:
HSP27 immunotherapy represents a novel means of lowering cholesterol and PCSK9 levels, primarily due to augmentation of LDLR expression and is associated with marked reductions in inflammation.
Is the World Redeemable? Anarchic Cosmopolitanism and Nation States in Franz Rosenzweig’s Messianism
Authors: Kajon Irene 
Published: April 2021

Abstract
Although in a sense a follower of both Isaiah and Machiavelli, Rosenzweig did not share their perception of a conflict between idealism and realism in human experience. His Star of Redemption advances a theory of the redemption of the world inspired by both Isaiah and Machiavelli, and at the same time critical of both of them – a theory in which ethics and politics are strongly connected but where ethics renounces the opposition to history and historical laws, and politics renounces the opposition to ethical ideas.
Is the World Redeemable? Contra Redemption
Authors: Mendes-Flohr Paul 
Published: April 2021

Abstract
At this juncture in history what is urgently needed, to state it rather paradoxically, is redemption from visions of redemption. In my brief reflections, I appeal for a studied, indeed resolute retreat from the very concept of redemption, in particular from its contemporary theological and secular iterations.
Is the Human Being Redeemable? A Meditation on Rosenzweig’s Claim That Death Is Very Good
Authors: Bielik-Robson Agata 
Published: April 2021

Abstract
In this article I claim there is no contradiction involved in Franz Rosenzweig’s love of life and his apology for death: what he loves and wants us to love is the finite life, life offered in its finitude which should in the end appear as enough – that is, sufficient and fit for everything we could want from life, redemption included. The beyond toward which death as the end gestures is not a promise of immortality, offering a transcendence in temporal terms infinitely prolonged. The will “to stay, to live,” of which Rosenzweig speaks in the opening paragraph of The Star of Redemption, is the drive characteristic of another finitude: desiring and investing in life, without, at the same time, wishing to prolong itself into infinity.
Is the Human Being Redeemable? A Self-Defeating Question
Authors: Liska Vivian 
Published: April 2021

Abstract
Rosenzweig’s pathos with respect to an ultimate redemption raises the question of the desirability of a state in which so much has to be undone in order to retain nothing but the One, the All, the Eternal, and the True. Similar doubts arise concerning Rosenzweig’s portrayal of the ways that this state of redemption is anticipated in life: through prayer, love of neighbor, the communal hymn of the We. How accessible are these to “the human being” as such? Rather than arguing against what appears as a grand remnant of the urge for totality, I invoke here two figures whose concepts of redemption partly resemble Rosenzweig’s, but depart from him in ways that make all the difference: Benjamin and Kafka.
Evolution and Development Strategy of Collaborative Innovation Network among Cities in the Yangtze River Delta-Based on Urban Innovation Index Data
Authors: Li Yan , Ye Mingque 
Published: April 2021

Abstract
The gravity model is applied to construct a collaborative innovation network between cities in the Yangtze River Delta, analyzes its structural characteristics and evolution from a network perspective, and proposes development strategies. This will help optimize the network structure of collaborative innovation among cities in the Yangtze River Delta, improve the efficiency of collaborative innovation, and promote their innovation level together. Based on the data of urban innovation indexes in 2006, 2011 and 2016, this paper reveals the structural characteristics and evolution of the collaborative innovation network between cities in the Yangtze River Delta, and puts forward corresponding development strategies. The findings are as follows: (1) The overall innovation capability of cities in the Yangtze River Delta has been continuously improved, and the strength of collaborative innovation links between cities has slowly increased. (2) The innovation development of cities in the Yangtze River Delta is unbalanced and asymmetrical. The network presents a significant “core-periphery” spatial structure and a “multi-center, multi-level” pattern, and central cities drive the development of surrounding cities. (3) A reasonable regional innovation community should be constructed from the perspectives of spatial coordination, innovation industry chain integration and resource sharing, and the collaborative innovation network should be optimized.
Negotiating Freedom: Mostašār od-Doule’s Yek kalame and the Iranian Constitutional Experience
Authors: Faridzadeh Ghazaleh , Faridzadeh Raed 
Published: April 2021

Abstract
Innumerable modernization measures were implemented in nineteenth-century Iran, in what might be called a process of translation. In the course of translating new ideas into the Iranian context by means of applying old expressions, Iranian legal language underwent sequences of change. To gain a better understanding of current struggles over the proper interpretation of some basic concepts, the paper seeks to explain how the concept of freedom was modified, by reference to Koselleck’s “space of experience” and the “horizon of expectation”. The analysis is based on Mostašār od-Doule’s treatise Yek kalame (“One word”), one of the most important nineteenth-century Iranian source texts, which greatly influenced the further development of the Iranian freedom movement.
Man, Land and Sea: Local Populations in Territorial and Maritime Disputes before the International Court of Justice
Authors: Suedi Yusra 
Published: April 2021

Abstract
The International Court of Justice routinely resolves territorial and maritime boundary disputes between States. Such disputes often carry repercussions for the lives and livelihoods of local populations living on the territories of the State litigants. This analysis seeks to examine the extent to which State litigants’ concerns for the impact of maritime disputes or territorial disputes on their local populations are factored into the Court’s decision-making process. It also seeks to identify reasons for the Court’s approach in such disputes, and to explore the potential role of the principle of equity in such contexts.
Inarticulate and Unconscious: Non-Justiciability before the International Court of Justice
Authors: John Anna 
Published: April 2021

Abstract
The International Court of Justice (ICJ) has explicitly rejected the notion that some disputes are non-justiciable. This article argues that despite these assertions, some disputes before the Court are de facto non-justiciable. The Court’s jurisprudence shows that techniques of avoidance are used when confronted with non-justiciable issues. These avoidance techniques include the dismissal of cases on technical grounds, and the partial or non-assertion of jurisdiction, which can result in conflicting or irreconcilable jurisprudence. The non-justiciability of disputes before the ICJ arises from the Court’s judicial function, which is in turn shaped by its institutional design and the scope of its powers. However, the use of avoidance techniques to confront non-justiciable disputes may raise questions about the fairness of dispute settlement before the ICJ.
Appointment and Dis-Appointment at the CJEU: Part I – The FV/Simpson Litigation
Authors: Bradley Kieran 
Published: April 2021

Abstract
This first part of a two-part article examines the rulings of the General Court and the Court of Justice concerning the irregular appointment in 2016 of a judge to the Union’s Civil Service Tribunal (now abolished). The CJEU was acting more or less in tandem with the European Court of Human Rights in the case of Ástráðsson v. Iceland; between them, these courts have confirmed for their respective legal orders that the right to a fair trial before a “tribunal established by law” includes a requirement that the judge(s) be appointed in accordance with the predetermined procedure. This requirement is not, however, absolute, but seeks ultimately to safeguard the independence and impartiality of the judiciary; it must therefore be balanced with other fundamental values, such as legal certainty and the irremovability of judges. The Simpson ruling may also have a certain resonance at the national level, as well as showcasing the CJEU’s remarkable “review” procedure, now in abeyance.
Mentoring Youth for Joy in Anxious Times
Authors: Cole Allan Hugh , Helsel Philip Browning 
Published: April 2021

Abstract
In this article, the authors set forward a theory of joy built upon adolescent development and describe how anxiety sometimes interferes. They elaborate why adolescence is a time of joy and the type of future-oriented adolescent imagination that fosters joy. Describing adolescent development from neurological, biological, social, sexual orientation, racial identity, and stages of faith perspectives, they show how joy and development are linked in adolescent flourishing. After defining anxiety, showing its prevalence, and distinguishing it from worry they indicate how the existential concerns of anxiety interferes with joy and how mentorship can help. Exploring pertinent Scriptures, they examine some ameliorative effects against anxiety through attachment based play that challenges a competitive culture and mentorship that evokes already-emergent strengths.
Keratoconus: cross-linking the window of the eye
Authors: Hayes Sally , Morgan Siân R. , Meek Keith M. 
Published: April 2021

Keratoconus is a condition in which the cornea progressively thins and weakens, leading to severe, irregular astigmatism and a significant reduction in quality of life. Although the precise cause of keratoconus is still not known, biochemical and structural studies indicate that overactive enzymes within the cornea break down the constituent proteins (collagen and proteoglycans) and cause the tissue to weaken. As the disease develops, collagen fibres slip past each other and are redistributed across the cornea, causing it to change shape. In recent years, it was discovered that the photochemical induction of cross-links within the corneal extracellular matrix, through the use of riboflavin and ultraviolet (UVA) light, could increase the strength and enzymatic resistance of the tissue and thereby halt keratoconus progression. Worldwide acceptance and use of riboflavin/UVA corneal cross-linking therapy for halting keratoconus progression has increased rapidly, in accordance with the growing body of evidence supporting its long-term effectiveness. This review focusses on the inception of riboflavin/UVA corneal cross-linking therapy for keratoconus, its clinical effectiveness and the latest scientific advances aimed at reducing patient treatment time, improving patient comfort and increasing patient eligibility for treatment. Plain language summary Review of current treatments using cross-linking to halt the progress of keratoconus Keratoconus is a disease in which the curved cornea, the transparent window at the front of the eye, weakens, bulges forward into a cone-shape and becomes thinner. This change of curvature means that light is not focussed onto the retina correctly and vision is progressively impaired. Traditionally, the effects of early keratoconus were alleviated by using glasses, specialist contact lenses, rings inserted into the cornea and in severe cases, by performing a corneal transplant. However, it was discovered that by inducing chemical bonds called cross-links within the cornea, the tissue could be strengthened and further thinning and shape changes prevented. The standard cross-linking procedure takes over an hour to perform and involves the removal of the cells at the front of the cornea, followed by the application of Vitamin B2 eye drops and low energy ultraviolet light (UVA) to create new cross-links within the tissue. Clinical trials have shown this standard procedure to be safe and effective at halting keratoconus progression. However, there are many treatment modifications currently under investigation that aim to reduce patient treatment time and increase comfort, such as accelerated cross-linking procedures and protocols that do not require removal of the surface cells. This review describes the different techniques being developed to carry out corneal cross-linking efficiently and painlessly, to halt keratoconus progression and avoid the need for expensive surgery.
ETV6-FLT3–positive myeloid/lymphoid neoplasm with eosinophilia presenting in an infant: an entity distinct from JMML
Authors: Spitzer Barbara , Dela Cruz Filemon S. , Ibanez Sanchez Glorymar D. , Zhang Yanming , Xiao Wenbin , Benayed Ryma , Markova Alina , Rodriguez-Sanchez M. Irene , Bouvier Nancy , Roshal Mikhail , Kung Andrew L. , Shukla Neerav 
Published: April 2021

Abstract
Myeloid/lymphoid neoplasm with eosinophilia (MLN-Eo) is a World Health Organization (WHO) established category of hematologic malignancies primarily arising in adults. We discuss an 8-month-old infant who presented with clinical features similar to those of juvenile myelomonocytic leukemia (JMML) but who was diagnosed with MLN-Eo driven by an ETV6-FLT3 fusion. Results of patient-derived leukemia ex vivo studies demonstrated increased sensitivity to type I FLT3 inhibitors as compared with type II inhibitors. Treatment with the type I inhibitor gilteritinib resulted in complete immunophenotypic and cytogenetic remission. This patient subsequently underwent a hematopoietic stem cell transplant and remains in complete remission 1 year later. This is the youngest patient reported with an ETV6-FLT3 fusion and adds to the mounting reports of FLT3-rearranged MLN-Eo, supporting its addition to the WHO classification. Furthermore, this case highlights the clinical utility of ex vivo drug testing of targeted therapies.
Healthyversusinflamed lung environments differentially affect mesenchymal stromal cells
Authors: Rolandsson Enes Sara , Hampton Thomas H. , Barua Jayita , McKenna David H. , dos Santos Claudia C. , Amiel Eyal , Ashare Alix , Liu Kathleen D. , Krasnodembskaya Anna D. , English Karen , Stanton Bruce A. , Rocco Patricia R.M. , Matthay Michael A. , Weiss Daniel J. 
Published: April 2021

BackgroundDespite increased interest in mesenchymal stromal cell (MSC)-based cell therapies for acute respiratory distress syndrome (ARDS), clinical investigations have not yet been successful and our understanding of the potentialin vivomechanisms of MSC actions in ARDS remains limited. ARDS is driven by an acute severe innate immune dysregulation, often characterised by inflammation, coagulation and cell injury. How this inflammatory microenvironment influences MSC functions remains to be determined.AimThe aim of this study was to comparatively assess how the inflammatory environment present in ARDS lungsversusthe lung environment present in healthy volunteers alters MSC behaviour.MethodsClinical-grade human bone marrow-derived MSCs (hMSCs) were exposed to bronchoalveolar lavage fluid (BALF) samples obtained from ARDS patients or from healthy volunteers. Following exposure, hMSCs and their conditioned media were evaluated for a broad panel of relevant properties, including viability, levels of expression of inflammatory cytokines, gene expression, cell surface human leukocyte antigen expression, and activation of coagulation and complement pathways.ResultsPro-inflammatory, pro-coagulant and major histocompatibility complex (self-recognition) related gene expression was markedly upregulated in hMSCs exposedex vivoto BALF obtained from healthy volunteers. These changes were less apparent and often opposite in hMSCs exposed to ARDS BALF samples.ConclusionThese data provide new insights into how hMSCs behave in healthyversusinflamed lung environments, and strongly suggest that the inflamed environment in ARDS induces hMSC responses that are potentially beneficial for cell survival and actions. This further highlights the need to understand how different disease environments affect hMSC functions.