bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of maternal HIV–HBV coinfection on pregnancy outcomes in an underdeveloped rural area of southwest China
Authors: Li Chunlin , Yang Yu , Wang Yingjian , Dong Shurong , Yang Ya , Shi Ying , Li Linhan , Jiang Feng , Chen Yue , Jiang Qingwu , Zhou Yibiao 
Published: January 2020

ObjectivesOur objective was to determine the impact of maternal HIV–hepatitis B virus (HBV) coinfection on pregnancy outcomes.MethodsThe current study was conducted in a county of Yi Autonomous Prefecture in southwest China. Data were abstracted from hospitalisation records, including maternal and infant information. The seroprevalences of HIV and HBV infections and HIV–HBV coinfection were determined and the impact of maternal HIV–HBV coinfection on adverse pregnancy outcomes was assessed using logistic regression analysis. A treatment effects linear regression model was also applied to examine the effect of HBV, HIV or coinfection to quantify the absolute difference in birth weight from a reference of HBV–HIV negative participants.ResultsA total of 13 198 pregnant women were included in our study, and among them, 99.1% were Yi people and 90.8% lived in rural area. The seroprevalences of HIV and HBV infections and HIV–HBV coinfection were 3.6% (95% CI: 3.2% to 3.9%), 3.2% (95% CI: 2.9% to 3.5%) and 0.2% (95% CI: 0.1% to 0.2%) among the pregnant women, respectively. Maternal HIV–HBV coinfection was a risk factor for low birth weight (adjusted OR (aOR)=5.52, 95% CI: 1.97 to 15.40). Compared with the HIV mono-infection group, the risk of low birth weight was significantly higher in the HIV–HBV coinfection group (aOR=3.62, 95% CI: 1.24 to 10.56). Maternal HIV infection was associated with an increased risk of low birth weight (aOR=1.90, 95% CI: 1.38 to 2.60) and preterm delivery (aOR=2.84, 95% CI: 1.81 to 4.47). Perinatal death was more common when mothers were infected with HBV (aOR=2.85, 95% CI: 1.54 to 5.26).ConclusionsThe prevalence of HIV infection was high among pregnant women of the Yi region. Both HIV and HBV infections might have adverse effects on pregnancy outcomes. Maternal HIV–HBV coinfection might be a risk factor for low birth weight in the Yi region, which needs to be confirmed.
Deformation of the seismogenic zone in the northeastern part of the Izu Peninsula, Japan, inferred from GNSS observations
Authors: Doke Ryosuke , Honda Ryou , Harada Masatake , Miyaoka Kazuki , Kato Teruyuki , Satomura Mikio 
Published: January 2020

Abstract
The Izu collision zone, which is characterized by the collision between the Izu-Bonin arc and the Honshu arc, is located in the northernmost part of the Philippine Sea Plate. Particularly in the northeastern margin of the zone, numerous large earthquakes have occurred throughout history. To clarify the convergent tectonics of this zone related to the occurrence of these large earthquakes, in this study we collected and analysed Global Navigation Satellite System (GNSS) observation data from the Izu collision zone. The result verified that a shear deformation zone exists in the northeastern part of the Izu Peninsula, which agrees with the maximum shear directions in the left-lateral slip of the active Kita-Izu Fault Zone in the study area. In the shear deformation zone, the seismic activities both in the eastern part of the Tanzawa Mountains and the northeastern part of the Izu Peninsula may be related to each other because the temporal patterns of the seismic activity in both areas are correlated. Based on the relative motion between the main part of the Izu Peninsula and the subducting forearc of the Philippine Sea Plate, the shear zone can be regarded as a transition zone affected by both plate collision and subduction.
Variations in sediment lithology of submarine flood deposits on the slope off Kumano River, Japan
Authors: Ikehara Ken , Usami Kazuko , Irino Tomohisa 
Published: January 2020

Abstract
Major river flooding is a typical geohazard frequently characterized by the transportation of large quantities of terrigenous material from the land to the sea. However, the types and patterns of flood material deposition and the influence on seafloor environments differ because of the diversity in geological and climatic conditions. In September 2011, the activity of typhoon 201112 produced severe rainfall in the central Kii Peninsula and caused a large flood along the Kumano River. The event was considered a once-in-a-century-scale flood. We examined the occurrence of flood deposits along the slope off the mouth of Kumano River in four surface sediment cores collected around 2 months after the 2011 flood. We found a thin and muddy event bed at the core top of three cores, with two or three event beds corresponding to past historical flood events. The sediment thickness, grain size and sedimentary structures for three historical flood deposits demonstrated significant variation. The thicknesses and the grain sizes of the three flood deposits from the same river showed no relationship with the maximum discharge from each flood. The differences in the types and fate of sediments discharge during the floods probably account for the variations.
Amorphous MnO2 Coated 3D Ni Nanomesh as a Thin-film Hybrid Cathode Material under O2 Atmosphere
Authors: Kee Yongho , Put Brecht , Bardé Fanny , Vereecken Philippe M. 
Published: January 2020

In this study, we apply the economically feasible liquid ALD process to deposit a 2 nm amorphous MnO2 thin-film on our high surface-area 3D Ni nanomesh substrate, which shows a high surface to footprint area ratio (30 cm2:1 cm2 for 1 μm thick Ni nanomesh), and demonstrate its preliminary electrochemical activity as a cathode under N2 and O2. The excellent footprint charge density and faradaic efficiency can be attributed to the catalytic oxygen reduction reaction, followed by Li-intercalation thus forming a hybrid combination of Li-ion and Li-O2 activity, alleviating the detrimental deactivation process of pristine MnO2.
Runx2 Deficiency in Osteoblasts Promotes Myeloma Progression by Altering the Bone Microenvironment at New Bone Sites
Authors: Xu Xiaoxuan , Zhang Chao , Trotter Timothy N. , Gowda Pramod S. , Lu Yun , Ponnazhagan Selvarangan , Javed Amjad , Li Juan , Yang Yang 
Published: January 2020

AbstractMultiple myeloma is a plasma cell malignancy that thrives in the bone marrow (BM), with frequent progression to new local and distant bone sites. Our previous studies demonstrated that multiple myeloma cells at primary sites secrete soluble factors and suppress osteoblastogenesis via the inhibition of Runt-related transcription factor 2 (Runx2) in pre- and immature osteoblasts (OB) in new bone sites, prior to the arrival of metastatic tumor cells. However, it is unknown whether OB-Runx2 suppression in new bone sites feeds back to promote multiple myeloma dissemination to and progression in these areas. Hence, we developed a syngeneic mouse model of multiple myeloma in which Runx2 is specifically deleted in the immature OBs of C57BL6/KaLwRij mice (OB-Runx2−/− mice) to study the effect of OB-Runx2 deficiency on multiple myeloma progression in new bone sites. In vivo studies with this model demonstrated that OB-Runx2 deficiency attracts multiple myeloma cells and promotes multiple myeloma tumor growth in bone. Mechanistic studies further revealed that OB-Runx2 deficiency induces an immunosuppressive microenvironment in BM that is marked by an increase in the concentration and activation of myeloid-derived suppressor cells (MDSC) and the suppression and exhaustion of cytotoxic CD8+ T cells. In contrast, MDSC depletion by either gemcitabine or 5-fluorouracil treatment in OB-Runx2−/− mice prevented these effects and inhibited multiple myeloma tumor growth in BM. These novel discoveries demonstrate that OB-Runx2 deficiency in new bone sites promotes multiple myeloma dissemination and progression by increasing metastatic cytokines and MDSCs in BM and inhibiting BM immunity. Importantly, MDSC depletion can block multiple myeloma progression promoted by OB-Runx2 deficiency.Significance: This study demonstrates that Runx2 deficiency in immature osteoblasts at distant bone sites attracts myeloma cells and allows myeloma progression in new bone sites via OB-secreted metastatic cytokines and MDSC-mediated suppression of bone marrow immunity.
miR-149 Suppresses Breast Cancer Metastasis by Blocking Paracrine Interactions with Macrophages
Authors: Sánchez-González Ismael , Bobien Anja , Molnar Christian , Schmid Simone , Strotbek Michaela , Boerries Melanie , Busch Hauke , Olayioye Monilola A. 
Published: January 2020

Abstract

Paracrine activation of cells contained in the tumor microenvironment promotes tumor progression and metastasis. In breast cancer, malignant cells recruit and educate macrophages into a M2 tumor–promoting phenotype that supports the metastatic spread of cancer cells. Here, we show that miR-149 functions as a metastasis-suppressing microRNA in breast cancer cells by limiting colony-stimulating factor-1 (CSF1)–dependent recruitment and M2 polarization of macrophages. In lymph node–positive, triple-negative breast cancer (TNBC) tissues, low miR-149 expression correlated with macrophage infiltration and reduced patient survival. By directly targeting CSF1, miR-149 expression in TNBC cell lines (MDA-MB-231 and BT-549) inhibited the recruitment of human monocytic THP-1 cells and primary human macrophages. Furthermore, in macrophages cocultured with MDA-MB-231 cells expressing miR-149, epidermal growth factor (EGF) and amphiregulin expression levels were strongly reduced, resulting in reduced EGF receptor activation in the cancer cells. In vivo, lung metastases developing from orthotopic MDA-MB-231 tumors were reduced by 75% by miR-149 expression, and this was associated with impaired M2 macrophage infiltration of the primary tumors. These data suggest that miR-149 downregulation functionally contributes to breast tumor progression by recruiting macrophages to the tumor and facilitating CSF1 and EGF receptor cross-talk between cancer cells and macrophages.

Significance:
These findings contribute to the understanding of tumor–stroma interactions by showing that miR-149 downregulation in TNBC enhances reciprocal growth factor signaling between macrophages and cancer cells, which promotes tumor progression and metastasis.
Inhibiting Translation Elongation with SVC112 Suppresses Cancer Stem Cells and Inhibits Growth in Head and Neck Squamous Carcinoma
Authors: Keysar Stephen B. , Gomes Nathan , Miller Bettina , Jackson Brian C. , Le Phuong N. , Morton J. Jason , Reisinger Julie , Chimed Tugs-Saikhan , Gomez Karina E. , Nieto Cera , Frederick Barbara , Pronk Gijsbertus J. , Somerset Hilary L. , Tan Aik-Choon , Wang Xiao-Jing , Raben David , Su Tin Tin , Jimeno Antonio 
Published: January 2020

Abstract

Cancer stem cells (CSC) drive growth, therapy resistance, and recurrence in head and neck squamous cell carcinoma (HNSCC). Regulation of protein translation is crucial for normal stem cells and CSCs; its inhibition could disrupt stemness properties, but translation inhibitors are limited clinically due to toxicity. SVC112 is a synthetic derivative of bouvardin, a plant-derived translation elongation inhibitor. SVC112 had greater antiproliferative effects on HNSCC cells compared with the FDA-approved translation inhibitor omacetaxine mepesuccinate (HHT). SVC112 preferentially inhibited cancer cells compared with patient-matched cancer-associated fibroblasts, whereas HHT was equally toxic to both. SVC112 reduced sphere formation by cell lines and CSCs. SVC112 alone inhibited the growth of patient-derived xenografts (PDX), and SVC112 combined with radiation resulted in tumor regression in HPV-positive and HPV-negative HNSCC PDXs. Notably, CSC depletion after SVC112 correlated with tumor response. SVC112 preferentially impeded ribosomal processing of mRNAs critical for stress response and decreased CSC-related proteins including Myc and Sox2. SVC112 increased cell-cycle progression delay and slowed DNA repair following radiation, enhancing colony and sphere formation radiation effects. In summary, these data demonstrate that SVC112 suppresses CSC-related proteins, enhances the effects of radiation, and blocks growth of HNSCC PDXs by inhibiting CSCs.

Significance:
Inhibiting protein elongation with SVC112 reduces tumor growth in head and neck squamous cell carcinoma and increases the effects of radiation by targeting the cancer stem cell pool.
Racial Differences in the Association Between Luminal Master Regulator Gene Expression Levels and Breast Cancer Survival
Authors: Byun Jung S. , Singhal Sandeep K. , Park Samson , Yi Dae Ik , Yan Tingfen , Caban Ambar , Jones Alana , Mukhopadhyay Partha , Gil Sara M. , Hewitt Stephen M. , Newman Lisa , Davis Melissa B. , Jenkins Brittany D. , Sepulveda Jorge L. , De Siervi Adriana , Nápoles Anna María , Vohra Nasreen A. , Gardner Kevin 
Published: January 2020

AbstractPurpose:Compared with their European American (EA) counterparts, African American (AA) women are more likely to die from breast cancer in the United States. This disparity is greatest in hormone receptor–positive subtypes. Here we uncover biological factors underlying this disparity by comparing functional expression and prognostic significance of master transcriptional regulators of luminal differentiation.Experimental Design:Data and biospecimens from 262 AA and 293 EA patients diagnosed with breast cancer from 2001 to 2010 at a major medical center were analyzed by IHC for functional biomarkers of luminal differentiation, including estrogen receptor (ESR1) and its pioneer factors, FOXA1 and GATA3. Integrated comparison of protein levels with network-level gene expression analysis uncovered predictive correlations with race and survival.Results:Univariate or multivariate HRs for overall survival, estimated from digital IHC scoring of nuclear antigen, show distinct differences in the magnitude and significance of these biomarkers to predict survival based on race: ESR1 [EA HR = 0.47; 95% confidence interval (CI), 0.31–0.72 and AA HR = 0.77; 95% CI, 0.48–1.18]; FOXA1 (EA HR = 0.38; 95% CI, 0.23–0.63 and AA HR = 0.53; 95% CI, 0.31–0.88), and GATA3 (EA HR = 0.36; 95% CI, 0.23–0.56; AA HR = 0.57; CI, 0.56–1.4). In addition, we identify genes in the downstream regulons of these biomarkers highly correlated with race and survival.Conclusions:Even within clinically homogeneous tumor groups, regulatory networks that drive mammary luminal differentiation reveal race-specific differences in their association with clinical outcome. Understanding these biomarkers and their downstream regulons will elucidate the intrinsic mechanisms that drive racial disparities in breast cancer survival.
Tumor Analyses Reveal Squamous Transformation and Off-Target Alterations As Early Resistance Mechanisms to First-line Osimertinib inEGFR-Mutant Lung Cancer
Authors: Schoenfeld Adam J. , Chan Joseph M. , Kubota Daisuke , Sato Hiroki , Rizvi Hira , Daneshbod Yahya , Chang Jason C. , Paik Paul K. , Offin Michael , Arcila Maria E. , Davare Monika A. , Shinde Ujwal , Pe'er Dana , Rekhtman Natasha , Kris Mark G. , Somwar Romel , Riely Gregory J. , Ladanyi Marc , Yu Helena A. 
Published: January 2020

AbstractPurpose:Patterns of resistance to first-line osimertinib are not well-established and have primarily been evaluated using plasma assays, which cannot detect histologic transformation and have differential sensitivity for copy number changes and chromosomal rearrangements.Experimental Design:To characterize mechanisms of resistance to osimertinib, patients with metastatic EGFR-mutant lung cancers who received osimertinib at Memorial Sloan Kettering Cancer Center and had next-generation sequencing performed on tumor tissue before osimertinib initiation and after progression were identified.Results:Among 62 patients who met eligibility criteria, histologic transformation, primarily squamous transformation, was identified in 15% of first-line osimertinib cases and 14% of later-line cases. Nineteen percent (5/27) of patients treated with first-line osimertinib had off-target genetic resistance (2 MET amplification, 1 KRAS mutation, 1 RET fusion, and 1 BRAF fusion) whereas 4% (1/27) had an acquired EGFR mutation (EGFR G724S). Patients with squamous transformation exhibited considerable genomic complexity; acquired PIK3CA mutation, chromosome 3q amplification, and FGF amplification were all seen. Patients with transformation had shorter time on osimertinib and shorter survival compared with patients with on-target resistance. Initial EGFR sensitizing mutation, time on osimertinib treatment, and line of therapy also influenced resistance mechanism that emerged. The compound mutation EGFR S768 + V769L and the mutation MET H1094Y were identified and validated as resistance mechanisms with potential treatment options.Conclusions:Histologic transformation and other off-target molecular alterations are frequent early emerging resistance mechanisms to osimertinib and are associated with poor clinical outcomes.See related commentary by Piotrowska and Hata, p. 2441
Diverse BRAF Gene Fusions Confer Resistance to EGFR-Targeted Therapy via Differential Modulation of BRAF Activity
Authors: Stangl Christina , Post Jasmin B. , van Roosmalen Markus J. , Hami Nizar , Verlaan-Klink Ingrid , Vos Harmjan R. , van Es Robert M. , Koudijs Marco J. , Voest Emile E. , Snippert Hugo J.G. , Kloosterman W.P. 
Published: January 2020

Abstract

Fusion genes can be oncogenic drivers in a variety of cancer types and represent potential targets for targeted therapy. The BRAF gene is frequently involved in oncogenic gene fusions, with fusion frequencies of 0.2%–3% throughout different cancers. However, BRAF fusions rarely occur in the same gene configuration, potentially challenging personalized therapy design. In particular, the impact of the wide variety of fusion partners on the oncogenic role of BRAF during tumor growth and drug response is unknown. Here, we used patient-derived colorectal cancer organoids to functionally characterize and cross-compare BRAF fusions containing various partner genes (AGAP3, DLG1, and TRIM24) with respect to cellular behavior, downstream signaling activation, and response to targeted therapies. We demonstrate that 5′ fusion partners mainly promote canonical oncogenic BRAF activity by replacing the auto-inhibitory N-terminal region. In addition, the 5′ partner of BRAF fusions influences their subcellular localization and intracellular signaling capacity, revealing distinct subsets of affected signaling pathways and altered gene expression. Presence of the different BRAF fusions resulted in varying sensitivities to combinatorial inhibition of MEK and the EGF receptor family. However, all BRAF fusions conveyed resistance to targeted monotherapy against the EGF receptor family, suggesting that BRAF fusions should be screened alongside other MAPK pathway alterations to identify patients with metastatic colorectal cancer to exclude from anti-EGFR–targeted treatment.

Implications:
Although intracellular signaling and sensitivity to targeted therapies of BRAF fusion genes are influenced by their 5′ fusion partner, we show that all investigated BRAF fusions confer resistance to clinically relevant EGFR inhibition.
Convexity Subarachnoid Hemorrhage Accompanied by Hyperacute Ischemic Stroke
Authors: Sato Takeo , Sakai Kenichiro , Mimori Masahiro , Komatsu Teppei , Sakuta Kenichi , Terasawa Yuka , Umehara Tadashi , Omoto Shusaku , Mitsumura Hidetaka , Murakami Hidetomo , Shimizu Tetsuya , Matsushima Satoshi , Iguchi Yasuyuki 
Published: January 2020

<b><i>Introduction and Objectives:</i></b> The clinical characteristics of convexity subarachnoid hemorrhage (cSAH) accompanying hyperacute ischemic stroke are unknown. We aimed to investigate the incidence and clinical characteristics of cSAH with hyperacute ischemic stroke. <b><i>Methods:</i></b> Participants comprised symptomatic ischemic stroke patients with ≤4.5 h from onset to door who also underwent initial MRI ≤4.5 h from onset. We reviewed initial and follow-up MRI during admission to identify cSAH. Retrospective reviews of cSAH incidence and clinical characteristics were performed. <b><i>Results:</i></b> We screened 1,249 consecutive symptomatic ischemic stroke patients, including 384 patients (279 males [73%]; median age, 67 years). Of the 384 patients, arterial ischemic stroke was seen in 382 patients, and venous ischemic stroke in 2 patients. Of the hyperacute arterial ischemic stroke, cSAH was identified within 4.5 h of ischemic stroke onset in 2 patients (0.5%) and around 6 days from ischemic stroke onset in 2 patients (0.5%). Of the hyperacute venous ischemic stroke, cSAH was observed in 1 patient on initial MRI. Comparing the clinical characteristics of hyperacute arterial ischemic stroke with and without cSAH, patients with cSAH were more likely to have arterial stenosis or occlusion ipsilateral to the cSAH (100 vs. 47%, <i>p</i> = 0.048), and the ischemic lesion only in the right hemisphere (100 vs. 33%, <i>p</i> = 0.013). In all cases, outcomes were favorable (modified Rankin Scale 0–1 at 3 months from onset). <b><i>Conclusions:</i></b> Convexity SAH was observed in 0.5% of hyperacute ischemic patients within 4.5 h of ischemic stroke onset and in 0.5% around 6 days from ischemic stroke onset.
An Investigation of the Precipitation Net Effect on the Particulate Matter Concentration in a Narrow Valley: Role of Lower-Troposphere Stability
Authors: Roldán-Henao Natalia , Hoyos Carlos D. , Herrera-Mejía Laura , Isaza Alejandra 
Published: January 2020

AbstractPrecipitation modulates the pollutant concentration in the atmosphere directly and indirectly through different mechanisms. Wet deposition, including in-cloud scavenging and below-cloud scavenging, is one of the main drivers of particulate matter removal from the atmosphere. Our focus is to assess the net effect of precipitation on the pollutant concentration using observations, a nonparametric conditional analysis, and the signed overlapping coefficient complement index. The study considers not only the direct near-surface aerosol below-cloud scavenging, but also the indirect effect associated with the induced lower-troposphere stability limiting the vertical dispersion, leading to a pollutant concentration increase. We consider the precipitation effects on fine and coarse particulate matter concentration. Probability density functions of the pollutant concentration during precipitation events and under dry conditions are analyzed for every hour of the day. The net effect of precipitation on the fine and coarse particulate matter concentration is strongly dependent on the atmospheric stability. During the nighttime and before midmorning, the atmosphere is stable; a precipitation event during this time induces below-cloud scavenging, reducing the concentration of particulate matter in the atmosphere. During the afternoon, unstable atmospheric conditions are predominant, and aerosols disperse vertically; a precipitation event during this period stabilizes the atmosphere, generating early stabilization that, together with the continued anthropogenic emissions during the day, leads to near-surface pollutant accumulation, offsetting the washout effect of the precipitation.