bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unraveling Triple-Negative Breast Cancer Tumor Microenvironment Heterogeneity: Towards an Optimized Treatment Approach
Authors: Bareche Yacine , Buisseret Laurence , Gruosso Tina , Girard Edwina , Venet David , Dupont Floriane , Desmedt Christine , Larsimont Denis , Park Morag , Rothé Françoise , Stagg John , Sotiriou Christos 
Published: October 2019

Abstract

Background
Recent efforts of gene expression profiling analyses recognized at least four different triple-negative breast cancer (TNBC) molecular subtypes. However, little is known regarding their tumor microenvironment (TME) heterogeneity.

Methods
Here, we investigated TME heterogeneity within each TNBC molecular subtype, including immune infiltrate localization and composition together with expression of targetable immune pathways, using publicly available transcriptomic and genomic datasets from a large TNBC series totaling 1512 samples. Associations between molecular subtypes and specific features were assessed using logistic regression models. All statistical tests were two-sided.

Results
We demonstrated that each TNBC molecular subtype exhibits distinct TME profiles associated with specific immune, vascularization, stroma, and metabolism biological processes together with specific immune composition and localization. The immunomodulatory subtype was associated with the highest expression of adaptive immune-related gene signatures and a fully inflamed spatial pattern appearing to be the optimal candidate for immune check point inhibitors. In contrast, most mesenchymal stem-like and luminal androgen receptor tumors showed an immunosuppressive phenotype as witnessed by high expression levels of stromal signatures. Basal-like, luminal androgen receptor, and mesenchymal subtypes exhibited an immune cold phenotype associated with stromal and metabolism TME signatures and enriched in margin-restricted spatial pattern. Tumors with high chromosomal instability and copy number loss in the chromosome 5q and 15q regions, including genomic loss of major histocompatibility complex related genes, showed reduced cytotoxic activity as a plausible immune escape mechanism.

Conclusions
Our results demonstrate that each TNBC subtype is associated with specific TME profiles, setting the ground for a rationale tailoring of immunotherapy in TNBC patients.
The Social Context of Media Trust: A Network Influence Model
Authors: Ognyanova Katherine 
Published: October 2019

Abstract
Concerns about the low public trust in U.S. media institutions have recently deepened amid increasing partisan polarization, large-scale digital disinformation campaigns, and frequent attacks on the press from political elites. This study explored the social factors that shape our trust in mainstream news sources. An examination of longitudinal network data from 13 residential student communities highlighted the importance of interpersonal influence on views about the media. The results show that the media trust of participants was predicted by the trust scores of their online and offline social contacts. The most robust and consistent effect comes from face-to-face interactions with politically like-minded conversation partners. Among online social ties, the analysis found effects from contact with others who distrust the media, but not from communication with people who reported high levels of media trust.
RPK1 and BAK1 sequentially form complexes with OST1 to regulate ABA-induced stomatal closure
Authors: Shang Yun , Yang Dami , Ha Yunmi , Shin Hyun-young , Nam Kyoung Hee 
Published: October 2019

Abstract
Regulation of plant water status occurs via abscisic acid (ABA)-induced stomatal closure. Open Stomata 1 (OST1) is a critical ABA signaling component regulating this process in guard cells. We previously reported that BRI1-associated receptor kinase 1 (BAK1) positively regulates ABA-induced stomatal closure by interacting with, and phosphorylating OST1. Here, we show that the Receptor-like Protein Kinase 1 (RPK1), previously known to be induced by ABA, is a positive ABA-signaling component in guard cell movement, and interacts with OST1. ABA-inducible expression patterns were observed in RPK1 and OST1, but not in BAK1. We investigated the underlying mechanisms by which the RPK1/OST1 and BAK1/OST1 complexes interact in stomatal guard cells by monitoring the complex formation continuously using FRET analyses. We found that the BAK1/OST1 complex was formed earlier than the RPK1/OST1 complex in response to ABA. In vitro and semi-in vivo kinase assays revealed that a trans-phosphorylation event occurred in the RPK1/OST1 complex, which differs from that in the BAK1/OST1 complex, wherein only OST1 phosphorylation occurred via BAK1. ABA Insensitive 1 (ABI1) only dephosphorylated OST1 in the BAK1/OST1 complex, but dephosphorylated both RPK1 and OST1 proteins in the RPK1/OST1 complex. Our results suggest that there are multiple coordinated ABA signaling systems to regulate stomatal movement.
OsCYP71D8L as a key regulator involved in growth and stress response by mediating gibberellins homeostasis in rice
Authors: Zhou Jiahao , Li Zeyu , Xiao Guiqing , Zhai Mingjuan , Pan Xiaowu , Huang Rongfeng , Zhang Haiwen 
Published: October 2019

Abstract
Phytohormones are pivotal in the regulation of plant growth and development, and acclimation to adverse environments. Multiple cytochrome P450 monooxygenases (CYP450s) are involved in the biosynthesis and catabolism of phytohormones. Here, we reported that a CYP450 member of CYP71 clan, OsCYP71D8L, participated in the control of multiple agronomic traits and abiotic stress responses by affecting gibberellin (GA) and cytokinin (CK) homeostasis in rice. We found that its gain-of-function mutant (cyp71d8l) and transgenic plants overexpressing OsCYP71D8L (OsCYP71D8L-OE) displayed similar phenotypes including dwarfed plant, reduced panicle length and grain number per panicle, and their endogenous GAs levels were notably decreased as compared to wild type (WT), respectively. Moreover, the dwarfed plant and less developed root of OsCYP71D8L-OE and cyp71d8l seedlings could be rescued by exogenous GA3 and lovastatin, but exacerbated by exogenous 6-BA. Importantly, OsCYP71D8L-OE and cyp71d8l seedlings maintained high chlorophyll contents and low reactive oxygen species level, and showed the enhanced tolerance to drought and salt stress compared with WT. Thus, our results suggest that OsCYP71D8L plays important roles in regulating rice growth and stress responses by coordinating GAs and CKs homeostasis, and it is useful to engineer stress-tolerant rice.
Chinua Achebe’sThere was a Countryand the digital publics of African literature
Authors: Yeku James 
Published: October 2019

AbstractA growing body of critical works on the digital expressions of African literature confirms the importance of digital literary studies in Africa. Examples of this growing scholarship include those of Shola Adenekan (2012) and Stephanie Santana (2018). Adenekan’s work focuses on ‘the Internetting of African literature’, while Santana's essay uses digital fiction from South Africa to offer a brilliant treatment of the connections between national spaces and digital networks. Several questions emerge, though, in considering how digital technologies reformulate the form, function, and audience of African literature. How are we, for instance, to understand the role of digital publics? What kind of ideological terrains emerge in online literary representations? What mediations do digital technologies bring to the changing forms and publics of contemporary writing in Africa? How does the ontology of the digital reconfigure the behaviour of the audience in the interpretation of literary meaning and how might previous scholarship such as those of Karin Barber’s on publics and audiences be read in the context of digitality? This article aims to answer these questions by examining some articulations of reader agency to Chinua Achebe’s There was a Country on digital avenues such as Facebook. Aside from an exploration of the intersection of digital culture and African literary forms, I hope to use online responses to Achebe’s memoir to track the trajectories of the new publics of African literature, showing how the ethnopolitics that greeted the publication of Achebe’s wartime narrative explicates the nature of digital publics
More Than Just Torsion: An Unusual Case of Testicular Pain
Authors: Martin Clyde Donald , Sulava Eric , Bloom Adam 
Published: October 2019

Abstract
Testicular pain has a wide differential and the nonspecific presentation should be triaged rapidly for urgent diagnosis and treatment. Scrotal pyoceles are uncommon collections of purulent fluid between the visceral and parietal tunica vaginalis, usually secondary to acute epididymo-orchitis, intra-abdominal infection, or trauma. Epididymitis and epididymo-orchitis are generally secondary to sexually transmitted infections or urinary tract pathogens. Epidymo-orchitis can compromise the testicular blood supply, leading to a microinfarction and rupture through the tunica albuginea; inflammatory and infectious material then translocate into the tunica vaginalis leading to the formation of a pyocele. Ultrasonography is the preferred method of diagnostic imaging, which can show a classic “falling snow” sign, loculations, or gas. The treatment for a scrotal pyocele is pain control, fluid resuscitation, broad-spectrum antibiotics, and early urology/general surgery consultation. In such cases, Fournier gangrene (FG) should be clinically ruled out and the presence of signs of Fournier gangrene should be met with an urgent surgical consult.
The histone variant H2A.Z in yeast is almost exclusively incorporated into the +1 nucleosome in the direction of transcription
Authors: Bagchi Dia N , Battenhouse Anna M , Park Daechan , Iyer Vishwanath R 
Published: October 2019

AbstractTranscription start sites (TSS) in eukaryotes are characterized by a nucleosome-depleted region (NDR), which appears to be flanked upstream and downstream by strongly positioned nucleosomes incorporating the histone variant H2A.Z. H2A.Z associates with both active and repressed TSS and is important for priming genes for rapid transcriptional activation. However, the determinants of H2A.Z occupancy at specific nucleosomes and its relationship to transcription initiation remain unclear. To further elucidate the specificity of H2A.Z, we determined its genomic localization at single nucleosome resolution, as well as the localization of its chromatin remodelers Swr1 and Ino80. By analyzing H2A.Z occupancy in conjunction with RNA expression data that captures promoter-derived antisense initiation, we find that H2A.Z’s bimodal incorporation on either side of the NDR is not a general feature of TSS, but is specifically a marker for bidirectional transcription, such that the upstream flanking −1 H2A.Z-containing nucleosome is more appropriately considered as a +1 H2A.Z nucleosome for antisense transcription. The localization of H2A.Z almost exclusively at the +1 nucleosome suggests that a transcription-initiation dependent process could contribute to its specific incorporation.
Immune biology of glioma associated macrophages and microglia: Functional and therapeutic implications
Authors: Wei Jun , Chen Peiwen , Gupta Pravesh , Ott Martina , Zamler Daniel , Kassab Cynthia , Bhat Krishna P , Curran Michael A , de Groot John F , Heimberger Amy B 
Published: October 2019

Abstract
CNS immune defenses are marshalled and dominated by brain resident macrophages and microglia, which are the innate immune sentinels and frontline host immune barriers against various pathogenic insults. These myeloid lineage cells are the predominant immune population in gliomas, and can constitute up to 30–50% of the total cellular composition. Parenchymal microglial cells and recruited monocyte-derived macrophages from the periphery exhibit disease specific phenotypic characteristics with spatial and temporal distinctions and are heterogeneous subpopulations based on their molecular signatures. A preponderance of myeloid over lymphoid lineage cells during CNS inflammation, including gliomas, is a contrasting feature of brain immunity relative to peripheral immunity. Herein we discuss glioma associated macrophage and microglia immune biology in the context of their identity, molecular drivers of recruitment, nomenclature and functional paradoxes, therapeutic reprogramming and polarization strategies, relevant challenges, and our perspectives on therapeutic modulation.
Ultrasound Ablation in Neurosurgery: Current Clinical Applications and Future Perspectives
Authors: Franzini Andrea , Moosa Shayan , Prada Francesco , Elias W Jeffrey 
Published: October 2019

Abstract
The concept of focusing high-intensity ultrasound beams for the purpose of cerebral ablation has interested neurosurgeons for more than 70 yr. However, the need for a craniectomy or a cranial acoustic window hindered the clinical diffusion of this technique. Recent technological advances, including the development of phased-array transducers and magnetic resonance imaging technology, have rekindled the interest in ultrasound for ablative brain surgery and have led to the development of the transcranial magnetic resonance-guided focused ultrasound (MRgFUS) thermal ablation procedure. In the last decade, this method has become increasingly popular, and its clinical applications are broadening. Despite the demonstrated efficacy of MRgFUS, transcranial thermal ablation using ultrasound is limited in that it can target exclusively the central region of the brain where the multiple acoustic beams are most optimally focused. On the contrary, lesioning of the cortex, the superficial subcortical areas, and regions close to the skull base is not possible with the limited treatment envelope of current phased-array transducers. Therefore, new ultrasound ablative techniques, which are not based on thermal mechanisms, have been developed and tested in experimental settings. This review describes the mechanisms by which these novel, nonthermal ablative techniques are based and also presents the current clinical applications of MRgFUS thermal ablation.
Y-Stent-Assisted Coiling With Low-Profile Neuroform Atlas Stents for Endovascular Treatment of Wide-Necked Complex Intracranial Bifurcation Aneurysms
Authors: Aydin Kubilay , Balci Sinan , Sencer Serra , Barburoglu Mehmet , Umutlu Muzaffer Reha , Arat Anil 
Published: October 2019

Abstract

BACKGROUND
Y-stent-assisted coiling is one of the eligible techniques for the treatment of complex bifurcation aneurysms. In majority of previous literature, Y-stenting has been performed using stents that could be delivered through large profile microcatheters that are often difficult to manipulate during navigation through sharply angled side branches. Attempts to navigate with these large profile catheters might cause serious complications during Y-stenting procedure.

OBJECTIVE
To investigate the safety, feasibility, and efficacy of Y-stent-assisted coiling procedure with Neuroform Atlas stents for the treatment of complex bifurcation aneurysms; Neuroform Atlas is a recently introduced open-cell stent that can be delivered though low-profile microcatheters.

METHODS
We identified the patients with intracranial bifurcation aneurysms treated by Y-stent-assisted coiling procedure with Neuroform Atlas stents. We assessed the immediate postoperative and follow-up clinical and angiographic outcomes. We also investigated the periprocedural and delayed complications.

RESULTS
A total of 30 aneurysms in 30 patients were included in the study. Y-stenting was successfully performed without any technical complications in all cases (100%). Immediate postprocedural angiography revealed total aneurysm occlusion in 83.3% of patients. The mean angiographic follow-up time was 11.8 mo. The last follow-ups showed complete occlusion in 93.3% of patients. There was no mortality in this study. A procedure-related complication developed in 6.7% and resulted in permanent morbidity in 3.3% of patients.

CONCLUSION
Neuroform Atlas stent combines the advantages of low-profile deployment microcatheters with an open-cell structure to achieve a successful Y-stenting procedure. Y-stent-assisted coiling with Neuroform Atlas stents provides a safe and effective endovascular treatment for wide-necked complex bifurcation aneurysms.
Pacific Lithosphere Evolution Inferred from Aitutaki Mantle Xenoliths
Authors: Snortum Eric , Day James M D , Jackson Matthew G 
Published: October 2019

Abstract
Highly siderophile element (HSE: Os, Ir, Ru, Pt, Pd, Re), major and trace element abundances, and 187Re–187Os systematics are reported for xenoliths and lavas from Aitutaki (Cook Islands), to investigate the composition of Pacific lithosphere. The xenolith suite comprises spinel-bearing lherzolites, dunite, and harzburgite, along with olivine websterite and pyroxenite. The xenoliths are hosted within nephelinite and alkali basalt volcanic rocks (187Os/188Os ∼0·1363 ± 13; 2SD; ΣHSE = 3–4 ppb). The volcanic host rocks are low-degree (2–5%) partial melts from the garnet stability field and an enriched mantle (EM) source. Pyroxenites have similar HSE abundances and Os isotope compositions (Al2O3 = 5·7–8·3 wt %; ΣHSE = 2–4 ppb; 187Os/187Os = 0·1263–0·1469) to the lavas. The pyroxenite and olivine websterite xenoliths directly formed from—or experienced extensive melt–rock interaction with—melts similar in composition to the volcanic rocks that host the xenoliths. Conversely, the Aitutaki lherzolites, harzburgites and dunites are similar in composition to abyssal peridotites with respect to their 187Os/188Os ratios (0·1264 ± 82), total HSE abundances (ΣHSE = 8–28 ppb) and major element abundances, forsterite contents (Fo89·9±1·2), and estimated extents of melt depletion (&lt;10 to &gt;15%). These peridotites are interpreted to sample relatively shallow Pacific mantle lithosphere that experienced limited melt–rock reaction and melting during ridge processes at ∼90 Ma. A survey of maximum time of rhenium depletion ages of Pacific mantle lithosphere from the Cook (Aitutaki ∼1·5 Ga), Austral (Tubuai’i ∼1·8 Ga), Samoan (Savai’i ∼1·5 Ga) and Hawaiian (Oa’hu ∼2 Ga) island groups shows that Mesoproterozoic to Neoproterozoic depletion ages are preserved in the xenolith suites. The variable timing and extent of mantle depletion preserved by the peridotites is, in some instances, superimposed by extensive and recent melt depletion as well as melt refertilization. Collectively, Pacific Ocean island mantle xenolith suites have similar distributions and variations of 187Os/188Os and HSE abundances to global abyssal peridotites. These observations indicate that Pacific mantle lithosphere is typical of oceanic lithosphere in general, and that this lithosphere is composed of peridotites that have experienced both recent melt depletion at ridges and prior and sometimes extensive melt depletion across several Wilson cycles spanning periods in excess of two billion years.
Fracture prevention: a population-based intervention delivered in primary care
Authors: Hoggard K , Hart S , Birchall J , Kirk S , Goff I , Grove M , Newton J 
Published: October 2019

Abstract

Background
Osteoporosis is common, increasing as the population ages and has significant consequences including fracture. Effective treatments are available.

Aim
To support proactive fracture risk assessment (FRAX) and optimizing treatment for high-risk patients in primary care.

Design
Clinical cohort

Setting
November 2017 to November 2018, support was provided to 71 practices comprising 69 of 90 practices within two National Health Service Clinical Commissioning Groups areas. Total population 579 508 (207 263 aged over 50 years).

Participants
FRAX (National Institute for Care and Clinical Excellence, NICE CG146) in (i) males aged 75 years and over, (ii) females aged 65 years and over, (iii) females aged under 65 years and males aged under 75 years with risk factors and (iv) under 50 years with major risk factors.

Results
A total of 158 946 met NICE CG146, 11 961 were coded with an osteoporosis diagnosis (7.5%), of those, 42% were prescribed treatment with a bone sparing agent (BSA). In total, 6942 were assessed to initiate BSA. Thirty percent of untreated osteoporosis diagnosis patients had never been prescribed BSA. Even when prescribed, 1700 people (35%) were for less than minimum recommended duration. Of the total 9784 patients within the FRAX recommended to treat threshold, 3197 (33%) were currently treated with BSA and 3684 (37%) had no history of ever receiving BSA. From untreated patients, expected incidence of 875 fractures over a 3-year period (approximately £3.4 million). Treatment would prevent 274 fractures (cost reduction: £1 274 045, with prescribing costs: saving £805 145 after 3 years of treatment).

Conclusion
Underdiagnosis and suboptimal treatment of osteoporosis was identified. Results suggest that implementing NICE guidance and optimizing treatment options in practice is possible and could prevent significant fractures.
IgA vasculitis and anti-GBM disease: two ends of a spectrum of immune complex vasculitis
Authors: Salama Alan D 
Published: October 2019

Abstract
Two immune complex vasculitides, IgA vasculitis (IgAV) and anti-GBM disease, represent polar extremes with regard to our understanding of disease pathogenesis, standardized management protocols and outcomes. This report compares our current approach to these uncommon entities in adults. Both diseases demonstrate degrees of small vessel necrosis and glomerular crescent formation. IgAV has an antibody response directed against unknown antigens, is often treated conservatively and has poorly studied long term renal outcomes. By contrast, anti-GBM disease presents with rapidly progressive glomerulonephritis and often results in end stage renal failure, despite intensive immunosuppression. Rarely, some cases of anti-GBM disease may be IgA predominant and bind other α-chains present in the GBM, but their clinical course is as for other anti-GBM disease patients but not IgAV, suggesting that the antigenic target rather than the antibody subclass is the critical factor in determining disease outcome. However, both conditions are associated with increased mortality in adults and result in significant chronic kidney disease and hypertension.
Role of Autophagy in Acquired Cholesteatoma
Authors: Li Quancheng , Ao Yinjie , Yu Qi , Zhou Shuihong 
Published: October 2019

Hypothesis:
Autophagy and its enhancement may have a role in the pathogenesis of acquired cholesteatoma.

Background:
The etiopathogenesis of acquired cholesteatoma remains unclear. Some clinical features of cholesteatoma are similar to those of cancer. The study of autophagy in cancer has indicated that enhanced autophagy enables tumor cell survival and growth.

Methods:
Cholesteatoma epithelium and normal external auditory canal (EAC) epithelium were obtained from patients with acquired cholesteatoma, and marginal epithelium of the tympanic membrane perforation was obtained from patients with chronic otitis media (COM). Immunohistochemistry (IHC) was performed to detect the expression of light chain 3 (LC3) in cholesteatoma and EAC epithelium. Western blotting (WB) was performed to detect the expression of LC3, Beclin-1, or the PI3K/AKT pathway in cholesteatoma, EAC, and COM epithelium.

Results:
LC3 staining of IHC was stronger in cholesteatoma epithelium compared with normal EAC epithelium. The ratios of LC3-II/I and Beclin-1 expression on WB were significantly higher in cholesteatoma epithelium compared with EAC epithelium or COM epithelium, and there was a significantly higher ratio of p-PI3K/PI3K and p-AKT/AKT in cholesteatoma epithelium compared with EAC epithelium.

Conclusions:
Enhanced autophagy might play a role in the pathogenesis of acquired cholesteatoma. PI3Ks might have different regulatory functions on autophagy in the cholesteatoma epithelium.