bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitomycin C treatment improves pancreatic islet graft longevity in intraportal islet transplantation by suppressing proinflammatory response
Authors: Yamane Kei , Anazawa Takayuki , Tada Seiichiro , Fujimoto Nanae , Inoguchi Kenta , Emoto Norio , Nagai Kazuyuki , Masui Toshihiko , Okajima Hideaki , Takaori Kyoichi , Sumi Shoichiro , Uemoto Shinji 
Published: July 2020

AbstractThe in vitro culture period prior to cell transplantation (i.e. pancreatic islet transplantation) enables cell modification and is thus advantageous. However, the islet preconditioning method has not been fully explored. Here we present a simple approach for islet preconditioning that uses the antibiotic mitomycin C (MMC), which has antitumor activity, to reduce islet immunogenicity and prevent proinflammatory events in an intraportal islet transplantation model. Freshly isolated mice islets were treated for 30 min with 10 μg/mL MMC or not, cultured for 20 h and transplanted into the livers of syngeneic or allogeneic diabetic mouse recipients. In the allogeneic model, MMC preconditioning significantly prolonged graft survival without requiring immunosuppressants. In vitro, MMC treatment suppressed the expression of proinflammatory cytokines in islet allografts, while immunohistochemical studies revealed the suppression of inflammatory cell infiltration into MMC-treated allografts relative to untreated allografts. Furthermore, MMC preconditioning significantly suppressed the mRNA expression of proinflammatory cytokines into the transplant site and induced the differentiation of regulatory T cells with the ability to suppress CD4+ T cell-mediated immune responses. In conclusion, islet preconditioning with MMC prolonged graft survival in an intraportal islet transplantation model by suppressing proinflammatory events and inducing potentially regulatory lymphocytes.
FPGS relapse-specific mutations in relapsed childhood acute lymphoblastic leukemia
Authors: Yu Sung-Liang , Zhang Hui , Ho Bing-Ching , Yu Chih-Hsiang , Chang Chia-Ching , Hsu Yin-Chen , Ni Yu-Ling , Lin Kai-Hsin , Jou Shiann-Tarng , Lu Meng-Yao , Chen Shu-Huey , Wu Kang-Hsi , Wang Shih-Chung , Chang Hsiu-Hao , Pui Ching-Hon , Yang Jun J. , Zhang Jinghui , Lin Dong-Tsamn , Lin Shu-Wha , Ma Xiaotu , Yang Yung-Li 
Published: July 2020

AbstractAlthough the cure rate for childhood acute lymphoblastic leukemia (ALL) has exceeded 80% with contemporary therapy, relapsed ALL remains a leading cause of cancer-related death in children. Relapse-specific mutations can be identified by comprehensive genome sequencing and might have clinical significance. Applying whole-exome sequencing to eight triplicate samples, we identified in one patient relapse-specific mutations in the folylpolyglutamate synthetase (FPGS) gene, whose product catalyzes the addition of multiple glutamate residues (polyglutamation) to methotrexate upon their entry into the cells. To determine the prevalence of mutations of the FPGS mutations, and those of two important genes in the thiopurine pathway, NT5C2 and PRPS1, we studied 299 diagnostic and 73 relapsed samples in 372 patients. Three more FPGS mutants were identified in two patients, NT5C2 mutations in six patients, and PRPS1 mutants in two patients. One patient had both NT5C2 and PRPS1 mutants. None of these alterations were detected at diagnosis with a sequencing depth of 1000X, suggesting that treatment pressure led to increased prevalence of mutations during therapy. Functional characterization of the FPGS mutants showed that they directly resulted in decreased enzymatic activity, leading to significant reduction in methotrexate polyglutamation, and therefore likely contributed to drug resistance and relapse in these cases. Thus, besides genomic alterations in thiopurine metabolizing enzymes, the relapse-specific mutations of FPGS represent another critical mechanism of acquired antimetabolite drug resistance in relapsed childhood ALL.
A novel method for assessing the renal biopsy specimens using an activatable fluorescent probe
Authors: Iyama Takuji , Takata Tomoaki , Yamada Kentaro , Mae Yukari , Taniguchi Sosuke , Ida Ayami , Ogawa Masaya , Yamamoto Marie , Hamada Shintaro , Fukuda Satoko , Kanda Tsutomu , Sugihara Takaaki , Isomoto Hajime , Urano Yasuteru 
Published: July 2020

AbstractGamma-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) is an activatable fluorescent probe that can be activated by γ-glutamyltranspeptidase (GGT). The expression of GGT in the kidney, which is one of the major organs exhibiting enhanced GGT expression, is exclusively localised to the cortex. Here, we aimed to investigate the feasibility of gGlu-HMRG as a probe for the on-site assessment of renal biopsy specimens. gGlu-HMRG fluorescent probe was applied to the renal proximal tubular epithelial cells and cortical collecting duct cells in vitro, mouse kidneys ex vivo, and human biopsy specimens. In addition, the fluorescence intensities in the cortex and the medulla were comparatively evaluated in the biopsy specimens. The fluorescence signal was rapidly detected in the renal proximal tubular epithelial cells, whereas that in the cortical collecting duct cells was not detected. The fluorescence signal was detected in the mouse kidneys ex vivo without markedly affecting the tissue morphology. In the human biopsy specimens, the fluorescence signal in the cortex was significantly distinct from that in the medulla (p < 0.05). Thus, this fluorescent probe can be used to distinctly identify the renal cortex in the biopsy specimens.
The histone lysine methyltransferase SETD8 regulates angiogenesis through HES-1 in human umbilical vein endothelial cells
Authors: Choi Dong Kyu , Kim Young Kyu , Park Sang Wook , Lee Heejin , Lee Seul , Kim Sang A. , Kim Soo Jin , Lee Junyeop , Kim Wanil , Min Sang-Hyun , Yu Ji Hoon 
Published: July 2020

AbstractHistone modifications, including histone lysine methylation, regulate gene expression in the vasculature, and targeting tumor blood vessels through histone modification decreases tumor growth. SETD8, a methyltransferase that catalyzes the mono-methylation of histone H4 lysine 20 is known to promote tumorigenesis in various cancers and its high levels of expression are related to poor prognosis. However, the detailed mechanisms by which SETD8 stimulates tumor progression and angiogenesis are still not well understood. Recent studies have demonstrated that, in vitro, BVT-948 efficiently and selectively suppresses SETD8 activity and histone methylation levels. In this study, we showed that BVT-948-mediated SETD8 inhibition in HUVECs results in an inhibition of angiogenesis. Inhibition of SETD8 not only inhibited angiogenesis but also disrupted actin stress fiber formation and induced cell cycle arrest at S phase. These effects were accompanied by increased HES-1 expression levels, decreased osteopontin levels, and a decreased differentiation of human induced pluripotent stem cells into endothelial cells. Interestingly, BVT-948 treatment reduced pathological angiogenesis in mouse OIR model. These data illustrate the mechanisms by which SETD8 regulates angiogenesis and may enable the use of a SETD8 inhibitor to treat various pathological conditions that are known to be associated with excessive angiogenesis, including and tumor growth.
Protostellar collapse: the conditions to form dust-rich protoplanetary disks
Authors: Lebreuilly U. , Commerçon B. , Laibe G. 
Published: July 2020

Context. Dust plays a key role during star, disk, and planet formation. Yet, its dynamics during the protostellar collapse remain a poorly investigated field. Recent studies seem to indicate that dust may decouple efficiently from the gas during these early stages.
Aims. We aim to understand how much and in which regions dust grains concentrate during the early phases of the protostellar collapse, and to see how this depends on the properties of the initial cloud and of the solid particles.
Methods. We used the multiple species dust dynamics MULTIGRAIN solver of the grid-based code RAMSES to perform various simulations of dusty collapses. We performed hydrodynamical and magnetohydrodynamical simulations where we varied the maximum size of the dust distribution, the thermal-to-gravitational energy ratio, and the magnetic properties of the cloud. We simulated the simultaneous evolution of ten neutral dust grain species with grain sizes varying from a few nanometers to a few hundreds of microns.
Results. We obtain a significant decoupling between the gas and the dust for grains of typical sizes of a few tens of microns. This decoupling strongly depends on the thermal-to-gravitational energy ratio, the grain sizes, and the inclusion of a magnetic field. With a semi-analytic model calibrated on our results, we show that the dust ratio mostly varies exponentially with the initial Stokes number at a rate that depends on the local cloud properties.
Conclusions. We find that larger grains tend to settle and drift efficiently in the first-core and in the newly formed disk. This can produce dust-to-gas ratios of several times the initial value. Dust concentrates in high-density regions (cores, disk, and pseudo-disk) and is depleted in low-density regions (envelope and outflows). The size at which grains decouple from the gas depends on the initial properties of the clouds. Since dust cannot necessarily be used as a proxy for gas during the collapse, we emphasize the necessity of including the treatment of its dynamics in protostellar collapse simulations.
The pocket-creation method may facilitate endoscopic submucosal dissection of large colorectal sessile tumors
Authors: Yamashina Takeshi , Hayashi Yoshikazu , Fukuda Hisashi , Okada Masahiro , Takezawa Takahito , Kobayashi Yasutoshi , Sakamoto Hirotsugu , Miura Yoshimasa , Shinozaki Satoshi , Sunada Keijiro , Lefor Alan Kawarai , Yamamoto Hironori 
Published: July 2020

Abstract
Background and study aims Resecting large colorectal sessile tumors using endoscopic submucosal dissection (ESD) is challenging because of severe submucosal fibrosis. Previously, we reported that ESD strategy using the pocket-creation method (PCM) is useful for large colorectal sessile tumors, but there are no large studies reporting the effectiveness and safety of the PCM for resection of large colorectal sessile tumors.
Patients and methods This was a retrospective review of 90 large colorectal sessile tumors in 89 patients who underwent ESD in our institution. Large colorectal sessile tumors were defined as polypoid lesions 20 mm or more in diameter. We divided them into PCM (n = 40) and conventional method (CM) groups (n = 50). The primary outcome measure was en bloc resection. The inverse-probability-treatment weighting (IPTW) approach was used to adjust for selection bias.
Results Both PCM and CM achieved high en bloc resection (100 % vs. 94 %, non-adjusted P = 0.25, IPTW-adjusted P = 0.19) and R0 resection rates (88 % vs. 78 %, non-adjusted P = 0.28, IPTW-adjusted P = 0.27). When PCM was used, the rate of pathologically negative vertical margins was significantly greater than with the CM (IPTW-adjusted P = 0.045). The dissection time was significantly shorter (IPTW-adjusted P = 0.025) and dissection speed faster (IPTW-adjusted P = 0.013) using the PCM than when the CM was used. There was no significant difference in the incidence of adverse events (intraprocedural perforation and delayed bleeding, IPTW-adjusted P = 0.68).
Conclusion Although en bloc resection and R0 resection rates were similar, PCM significantly increased the rate of negative vertical margins with rapid dissection for treatment of large colorectal sessile tumors.
Radiation-Induced Cervical Spinal Cord Cavernoma Following Head and Neck Radiotherapy: Case Report
Authors: Al-Jehani Hosam , Najjar Ahmad , Barnawi Abdulwahid , Shedid Daniel 
Published: July 2020

AbstractCavernous angiomas are congenital vascular malformations that affect the central nervous system. Reports implicated radiation therapy as a triggering factor for the formation of cavernomas but not in relation with head and neck radiation therapy. Radiation-induced cavernomas (RIC) should be considered in the differential diagnosis of focal neurological symptoms in any patient who has received previous cranial-spinal or head and neck radiotherapy.
Dynamic Oromandibular Reconstructions Using Chimeric Fibular and Gracilis or Vastus Lateralis Free Flaps
Authors: Kim Min Ji , Choi Jong Woo , Jeong Woo Shik , Nam Soon Yuhl , Choi Seung Ho 
Published: July 2020

Abstract
Background Despite efforts of head and neck functional reconstruction, anatomic restoration has been used until now. This article describes our experience of using a chimeric free fibular osteocutaneous flap conjoined with a functional muscle free flap, defined as dynamic oromandibular reconstruction.
Methods Through a retrospective chart review, four consecutive patients who underwent reconstruction with a total fibular free flap were included. The former two patients underwent reconstruction using a conventional osteocutaneous free fibular flap. The latter two patients had an oromandibular defect after cancer resection and underwent dynamic oromandibular reconstruction with a chimeric free fibular flap conjoined with a gracilis free flap or vastus lateralis muscle free flap.
Results In the speech analysis, the dynamic group revealed a satisfactory tongue movement. Protrusion and lateralization were the most different movement changes. The tongue range of motion score was 62.5 in the dynamic group and 25.0 in the control group. On the dynamic magnetic resonance imaging, the contact of the soft palate with the tongue was excellent, and the epiglottis closure during deglutition was complete. In the three-dimensional volumetric analysis of mandibular aesthetic contouring, the dynamic group showed a much smaller difference in hemifacial volume, with a difference of 73.7 mL in the dynamic group and 101.76 mL in the control group.
Conclusion This study is a preliminary trial of dynamic oromandibular reconstruction using chimeric free fibular flaps with functional muscle transfer. We demonstrated the possibility of dynamic oromandibular reconstruction, which enhanced more functional aspects in the patients in this study.
The carbon footprint of household energy use in the United States
Authors: Goldstein Benjamin , Gounaridis Dimitrios , Newell Joshua P. 
Published: July 2020

Significance
This study uses data on ∼93 million individual homes to perform the most comprehensive study of greenhouse gases from residential energy use in the United States. We provide nationwide rankings of carbon intensity of homes in states and ZIP codes and offer correlations between affluence, floor space, and emissions. Scenarios demonstrate this sector cannot achieve the Paris Agreement 2050 target by decarbonizing electricity production alone. Meeting this target will also necessitate a broad portfolio of zero emission energy solutions and behavioral change associated with housing preferences. To support policy, we estimate the reductions in floor space and increases in density needed to build low-carbon communities.
Human cytomegalovirus protein pUL36: A dual cell death pathway inhibitor
Authors: Fletcher-Etherington Alice , Nobre Luis , Nightingale Katie , Antrobus Robin , Nichols Jenna , Davison Andrew J. , Stanton Richard J. , Weekes Michael P. 
Published: July 2020

Significance
Cell death is a key defense against viral infection, preventing spread from infected to uninfected cells. Correspondingly, certain viruses encode inhibitors of apoptotic and necroptotic cell death pathways in order to facilitate their persistence. Human cytomegalovirus (HCMV) is an important human pathogen that can block apoptosis, but hitherto it has been unclear whether or how the virus blocks necroptosis. Here, we used a proteomic screen to identify human proteins targeted for destruction by HCMV, finding that the key necroptosis mediator MLKL is degraded throughout infection. MLKL is targeted for degradation by HCMV protein pUL36, which is also instrumental in inhibiting apoptosis. Thus, pUL36 is a dual cell death pathway inhibitor, and may represent an important therapeutic target.
FOXO transcription factors activate alternative major immediate early promoters to induce human cytomegalovirus reactivation
Authors: Hale Andrew E. , Collins-McMillen Donna , Lenarcic Erik M. , Igarashi Suzu , Kamil Jeremy P. , Goodrum Felicia , Moorman Nathaniel J. 
Published: July 2020

SignificanceHuman cytomegalovirus (HCMV) infection is lifelong and persistent. Periodic reactivation of cytomegalovirus poses serious disease risk for immune-compromised patients. A critical driver of reactivation is expression of viral genes from the major immediate early locus. Recent paradigm-shifting evidence shows that reactivation is driven from promoters distinct from those that drive replication in permissive cells. Understanding the contextual control of these promoters and how they specifically respond to cellular cues that drive reactivation is critical for establishing future therapies that prevent reactivation. Our findings mechanistically define a previously enigmatic relationship between differentiation and reactivation and provide potential targets for therapeutic intervention to prevent HCMV reactivation and disease.
Robust evidence for bisexual orientation among men
Authors: Jabbour Jeremy , Holmes Luke , Sylva David , Hsu Kevin J. , Semon Theodore L. , Rosenthal A. M. , Safron Adam , Slettevold Erlend , Watts-Overall Tuesday M. , Savin-Williams Ritch C. , Sylla John , Rieger Gerulf , Bailey J. Michael 
Published: July 2020

Significance
There has long been skepticism among both scientists and laypersons that male bisexual orientation exists. Skeptics have claimed that men who self-identify as bisexual are actually homosexual or heterosexual. (The existence of female bisexuality has been less controversial.) This controversy can be resolved using objective, genital responses of men to male and female erotic stimuli. We combined nearly all available data (from eight previous American, British, and Canadian studies) to form a dataset of more than 500 men, much larger than any previous individual study, and conducted rigorous statistical tests. Results provided compelling evidence that bisexual-identified men tend to show bisexual genital and subjective arousal patterns. Male sexual orientation is expressed on a continuum rather than dichotomously.
Molecular basis of Coxsackievirus A10 entry using the two-in-one attachment and uncoating receptor KRM1
Authors: Cui Yingzi , Peng Ruchao , Song Hao , Tong Zhou , Qu Xiao , Liu Sheng , Zhao Xin , Chai Yan , Wang Peiyi , Gao George F. , Qi Jianxun 
Published: July 2020

Significance
CV-A10 is one of the major causative agents of hand-foot-mouth disease, an acute febrile disease occurring mainly in children. To date, there are no effective vaccines or therapeutic drugs available for CV-A10 infection. Moreover, knowledge of the mechanisms of CV-A10 infection and pathogenesis, which are crucial for prevention and treatment of the related diseases, is incomplete. In this work, we provide comprehensive mechanistic insight into CV-A10 infection using the receptor KRM1, demonstrating that KRM1 acts as a two-in-one attachment and uncoating receptor for CV-A10 entry, which mediates both viral attachment at the cell surface and uncoating in the endosome. This work expands our understanding on the mechanism of nonenveloped virus infection and reveals new clues for antiviral intervention.
Lay theories of peace and their influence on policy preference during violent conflict
Authors: Leshem Oded Adomi , Halperin Eran 
Published: July 2020

SignificanceMost people embroiled in violent intergroup conflict have sincere desires for peace. Yet, we show that, even in its abstract form, the concept of peace encompasses different interpretations, each influenced by the perceiver’s experiences of conflict, and each shaping the way in which the perceiver thinks about conflict resolution. Using original data collected in Israel, the West Bank, and the Gaza Strip, we provide insights about how lay theories of peace are associated with the power structure of the conflict and how they predict citizens’ preferences for solving their long-standing dispute by either dividing resources or sharing them.
Last step in the path of LDL cholesterol from lysosome to plasma membrane to ER is governed by phosphatidylserine
Authors: Trinh Michael N. , Brown Michael S. , Goldstein Joseph L. , Han Jaeil , Vale Gonçalo , McDonald Jeffrey G. , Seemann Joachim , Mendell Joshua T. , Lu Feiran 
Published: July 2020

Significance
Feedback control of cholesterol metabolism is essential for cell viability and prevention of heart attacks. Cells acquire cholesterol from receptor-mediated uptake of low-density lipoprotein, which delivers cholesterol to lysosomes. To exert feedback control, cholesterol must reach the endoplasmic reticulum (ER). Here we use a CRISPR screen to show that lysosome-derived cholesterol moves first to the plasma membrane and then to the ER. The last movement requires an enzyme that produces phosphatidylserine. This demonstrates that transmembrane movement of one lipid (cholesterol) requires another lipid (phosphatidylserine). Our results explain how one organelle (ER) monitors the cholesterol content of another organelle (plasma membrane), thereby maintaining membrane integrity and ensuring cell survival.
On the Dutch temporal adverbial goed en wel
Authors: Hoeksema Jack , van der Wouden Ton 
Published: July 2020

Abstract
The paper investigates the origin, the development, the semantics and the pragmatics of the temporal use of the
Dutch expression goed en wel ‘good and well’. We argue that the expression has developed from a meaning “safe and
sound” into an indicator of the end of a preparatory phase or transition period, as well as a marker of the beginning of a new
state. We observe that temporal goed en wel always requires a secondary state of affairs that is temporally
related to the transition point initiating the primary state of affairs, and we show that the expression is increasingly being
employed for rhetorical purposes.
Syntax of the Palestinian Arabic negation-associated exclusive construction
Authors: Khalaily Samir 
Published: July 2020

Abstract
This paper presents an analysis of a Palestinian Arabic negation-associated exclusive construction featuring the
contrastive focus marker illa ‘but’, with theoretical implications for the syntax of negation, negative polarity
item licensing, and the categorical status of the root in sentential syntax. It analyzes illa-phrases as
constituents licensed by a c-commanding sentential negation (Neg), and illa as a grammatical device encoding
contrastiveness. A crucial source for the exclusive semantics of the construction comes from a silent bass ‘only’
immediately following illa that constitutes a syntactic ‘shield’ against Neg scope. Rather than taking an
in-situ focus-interpretation approach (cf. Rooth 1985, 1992), we argue for two covert movements at the syntax-semantics interface:
quantifier raising of illa-phrases to the designated specifier of polarity Phrase followed by
Polarity-to-Focus-raising of Neg. This creates the right syntactic configuration for the truth conditional import of both
operators and captures the ‘classical’ thought that focus-sensitive exclusive operators like only quantify over
propositional alternatives.