bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reading across writing systems: A meta-analysis of the neural correlates for first and second language reading
Authors: Li Hehui , Zhang Jia , Ding Guosheng 
Published: January 2021

AbstractNumerous studies have investigated the neural correlates of reading in two languages. However, reliable conclusions have not been established as to the relationship of the neural correlates underlying reading in the first (L1) and second (L2) language. Here, we conduct meta-analyses to address this issue. We found that compared to L1, the left inferior parietal lobule showed greater activation during L2 processing across all bilingual studies. We then divided the literature into two categories: bilingual participants who learned two languages with different writing systems and bilinguals who learned two languages with similar writing systems. We found that language differences in the neural correlates of reading were generally modulated by writing system similarity, except the region of the left inferior parietal lobule, which showed preferences for L2 reading in both types of bilinguals. These findings provide new insights into the brain mechanisms underlying reading in bilinguals.
Diet and risk of gastro-oesophageal reflux disease in the Melbourne Collaborative Cohort Study
Authors: Wang Sabrina E , Hodge Allison M , Dashti S Ghazaleh , Dixon-Suen Suzanne C , Mitchell Hazel , Thomas Robert JS , Williamson Elizabeth M , Makalic Enes , Boussioutas Alex , Haydon Andrew M , Giles Graham G , Milne Roger L , Kendall Bradley J , English Dallas R 
Published: January 2021

AbstractObjective:To examine associations between diet and risk of developing gastro-oesophageal reflux disease (GERD).Design:Prospective cohort with a median follow-up of 15·8 years. Baseline diet was measured using a FFQ. GERD was defined as self-reported current or history of daily heartburn or acid regurgitation beginning at least 2 years after baseline. Sex-specific logistic regressions were performed to estimate OR for GERD associated with diet quality scores and intakes of nutrients, food groups and individual foods and beverages. The effect of substituting saturated fat for monounsaturated or polyunsaturated fat on GERD risk was examined.Setting:Melbourne, Australia.Participants:A cohort of 20 926 participants (62 % women) aged 40–59 years at recruitment between 1990 and 1994.Results:For men, total fat intake was associated with increased risk of GERD (OR 1·05 per 5 g/d; 95 % CI 1·01, 1·09; P = 0·016), whereas total carbohydrate (OR 0·89 per 30 g/d; 95 % CI 0·82, 0·98; P = 0·010) and starch intakes (OR 0·84 per 30 g/d; 95 % CI 0·75, 0·94; P = 0·005) were associated with reduced risk. Nutrients were not associated with risk for women. For both sexes, substituting saturated fat for polyunsaturated or monounsaturated fat did not change risk. For both sexes, fish, chicken, cruciferous vegetables and carbonated beverages were associated with increased risk, whereas total fruit and citrus were associated with reduced risk. No association was observed with diet quality scores.Conclusions:Diet is a possible risk factor for GERD, but food considered as triggers of GERD symptoms might not necessarily contribute to disease development. Potential differential associations for men and women warrant further investigation.
Three‐Dimensional Numerical Simulations of Internal Tides in the Angolan Upwelling Region
Authors: Zeng Z. , Brandt P. , Lamb K. G. , Greatbatch R. J. , Dengler M. , Claus M. , Chen X. 
Published: January 2021

AbstractIn austral winter, biological productivity at the Angolan shelf reaches its maximum. The alongshore winds, however, reach their seasonal minimum suggesting that processes other than local wind‐driven upwelling contribute to near‐coastal cooling and upward nutrient supply, one possibility being mixing induced by internal tides (ITs). Here, we apply a three‐dimensional ocean model to simulate the generation, propagation, and dissipation of ITs at the Angolan continental slope and shelf. Model results are validated against moored acoustic Doppler current profiler and other observations. Simulated ITs are mainly generated in regions with a critical/supercritical slope typically between the 200‐ and 500‐m isobaths. Mixing induced by ITs is found to be strongest close to the coast and gradually decreases offshore thereby contributing to the establishment of cross‐shore temperature gradients. The available seasonal coverage of hydrographic data is used to design simulations to investigate the influence of seasonally varying stratification characterized by low stratification in austral winter and high stratification in austral summer. The results show that IT characteristics, such as their wavelengths, sea surface convergence patterns, and baroclinic structure, have substantial seasonal variations and additionally strong spatial inhomogeneities. However, seasonal variations in the spatially averaged generation, onshore flux, and dissipation of IT energy are weak. By evaluating the change of potential energy, it is shown, nevertheless, that mixing due to ITs is more effective during austral winter. We argue that this is because the weaker background stratification in austral winter than in austral summer acts as a preconditioning for IT mixing.
High‐Speed Spectra of a Bolt From the Blue Lightning Stepped Leader
Authors: Harley Jacob , Zimmerman Lucy A. , Edens Harald E. , Stenbaek‐Nielsen Hans C. , Haaland Ryan K. , Sonnenfeld Richard G. , McHarg Matthew G. 
Published: January 2021

AbstractWe present spectra from 400 to 900 nm of a bolt from the blue stepped leader on July 19, 2015 including novel observations from 400 to 600 nm. The spectra of the luminous steps near the tip of the leader look qualitatively similar and contain singly ionized nitrogen lines. The presence of these ionized lines indicate currents and temperatures comparable to peak return stroke. The entire channel illuminates over the final 1.3 ms before attachment, but does not contain evidence of ionization. This neutral spectrum is qualitatively similar to the return stroke spectrum after peak current. This may indicate increasing potential and current along the channel prior to attachment.
Brain dynamics: the temporal variability of connectivity, and differences in schizophrenia and ADHD
Authors: Rolls Edmund T. , Cheng Wei , Feng Jianfeng 
Published: January 2021

AbstractWe describe advances in the understanding of brain dynamics that are important for understanding the operation of the cerebral cortex in health and disease. In data from 1017 participants from the Human Connectome Project, we show that early visual and connected areas have low temporal variability of their functional connectivity. We show that a low temporal variability of the connectivity of cortical areas is related to high mean functional connectivity between those areas, and provide an account of how these dynamics arise. We then investigate how these concepts help to understand brain dynamics in mental disorders. We find that in both first episode and long-term schizophrenia, reduced functional connectivity of early visual and related temporal cortex areas is associated with increased temporal variability of the functional connectivity, consistent with decreased stability of attractor networks related to sensory processing. In ADHD, we find these functional connectivities are increased and their temporal variability is decreased, and relate this to increased engagement with visual sensory input as manifest in high screen time usage in ADHD. We further show that these differences in the dynamics of the cortex in schizophrenia, and ADHD can be related to differences in the functional connectivity of the specific sensory vs. association thalamic nuclei. These discoveries help to advance our understanding of cortical operation in health, and in some mental disorders.
How effective and cost-effective is water fluoridation for adults? Protocol for a 10-year retrospective cohort study
Authors: Moore Deborah , Allen Thomas , Birch Stephen , Tickle Martin , Walsh Tanya , Pretty Iain A. 
Published: January 2021

Abstract
Background
Tooth decay can cause pain, sleepless nights and loss of productive workdays. Fluoridation of drinking water was identified in the 1940s as a cost-effective method of prevention. In the mid-1970s, fluoride toothpastes became widely available. Since then, in high-income countries the prevalence of tooth decay in children has reduced whilst natural tooth retention in older age groups has increased. Most water fluoridation research was carried out before these dramatic changes in fluoride availability and oral health. Furthermore, there is a paucity of evidence in adults. The aim of this study is to assess the clinical and cost-effectiveness of water fluoridation in preventing invasive dental treatment in adults and adolescents aged over 12.

Methods/design
Retrospective cohort study using 10 years of routinely available dental treatment data. Individuals exposed to water fluoridation will be identified by sampled water fluoride concentration linked to place of residence. Outcomes will be based on the number of invasive dental treatments received per participant (fillings, extractions, root canal treatments). A generalised linear model with clustering by local authority area will be used for analysis. The model will include area level propensity scores and individual-level covariates. The economic evaluation will focus on (1) cost-effectiveness as assessed by the water fluoridation mean cost per invasive treatment avoided and (2) a return on investment from the public sector perspective, capturing the change in cost of dental service utilisation resulting from investment in water fluoridation.

Discussions
There is a well-recognised need for contemporary evidence regarding the effectiveness and cost-effectiveness of water fluoridation, particularly for adults. The absence of such evidence for all age groups may lead to an underestimation of the potential benefits of a population-wide, rather than targeted, fluoride delivery programme. This study will utilise a pragmatic design to address the information needs of policy makers in a timely manner.
Clinical utility of circulating tumour cell-based monitoring of late-line chemotherapy for metastatic breast cancer: the randomised CirCe01 trial
Authors: Cabel Luc , Berger Frédérique , Cottu Paul , Loirat Delphine , Rampanou Aurore , Brain Etienne , Cyrille Stacy , Bourgeois Hugues , Kiavue Nicolas , Deluche Elise , Ladoire Sylvain , Campone Mario , Pierga Jean-Yves , Bidard Francois-Clement 
Published: January 2021

Abstract
Background
CirCe01 trial aimed to assess the clinical utility of circulating tumour cell (CTC)-based monitoring in metastatic breast cancer (MBC) patients beyond the third line of chemotherapy (LC).

Methods
CirCe01 was a prospective, multicentre, randomised trial (NCT01349842) that included patients with MBC after two systemic LC. Patients with ≥5 CTC/7.5 mL (CellSearch®) were randomised between the CTC-driven and the standard arm. In the CTC arm, changes in CTC count were assessed at the first cycle of each LC; patients in whom CTC levels predicted early tumour progression had to switch to a subsequent LC.

Results
Greater than or equal to 5 CTC/7.5 mL were observed in N = 101/204 patients. In the CTC arm (N = 51), 43 (83%) and 18 (44%) patients completed CTC monitoring in the third and fourth lines, respectively, and 18 (42%) and 11 (61%) of these patients, respectively, had no CTC response. Thirteen (72%) and 5 (46%) of these patients underwent early switch to the next LC. Overall survival was not different between the two arms (hazard ratio = 0.95, 95% confidence interval = [0.6;1.4], p = 0.8). In subgroup analyses, patients with no CTC response who switched chemotherapy experienced longer survival than patients who did not.

Conclusions
Due to the limited accrual and compliance, this trial failed to demonstrate the clinical utility of CTC monitoring.

Clinical Trial Registration
NCT, NCT01349842, https://clinicaltrials.gov/ct2/show/NCT01349842, registered 9 May 2011.
Natural history, response to systemic therapy, and genomic landscape of plasmacytoid urothelial carcinoma
Authors: Teo Min Yuen , Al-Ahmadie Hikmat , Seier Kenneth , Tully Christopher , Regazzi Ashley M. , Pietzak Eugene , Solit David B. , Tickoo Satish , Reuter Victor , Cha Eugene K. , Herr Harry , Donahue Timothy , Donat Sherri M. , Dalbagni Guido , Bochner Bernard H. , Funt Samuel , Iyer Gopakumar V. , Bajorin Dean F. , Ostrovnaya Irina , Rosenberg Jonathan E. 
Published: January 2021

Abstract
Background
Plasmacytoid urothelial carcinoma (PUC) is a rare, aggressive histologic variant of urothelial cancer characterised by a diffuse growth pattern and CDH1 mutation. We studied the efficacy of preoperative platinum-based chemotherapy in nonmetastatic PUC and immune checkpoint inhibitors (ICIs) in advanced PUC.

Methods
Cases of nonmetastatic PUC and advanced PUC treated with ICIs at our institution were identified. Outcomes were compared to those of a published cohort of patients with urothelial carcinoma not otherwise specified.

Results
We identified 81 patients with nonmetastatic PUC. Of the patients with localised disease who underwent neoadjuvant chemotherapy, pathologic complete response and downstaging rates were 12 and 21%, respectively. Pathologic downstaging was not associated with significant improvement in clinical outcomes. Up to 18% of localised disease and 28% of locally advanced cases had unresectable disease at the time of surgery. ICI-treated advanced PUC (N = 21) had progression-free and overall survival of 4.5 and 10.5 months, respectively, and a 38% response rate. FGFR3 and DNA damage response gene alterations were observed in 3 and 15% of cases, respectively.

Conclusions
PUC is associated with high disease burden and poor chemosensitivity. Increased awareness and recognition of this disease variant will allow for new treatment strategies.
Circular RNA circRUNX1 promotes papillary thyroid cancer progression and metastasis by sponging MiR-296-3p and regulating DDHD2 expression
Authors: Chu Junjie , Tao Li , Yao Teng , Chen Zizheng , Lu Xiaoxiao , Gao Li , Fang Liang , Chen Jian , He Gaofei , Shen Shuying , Zhang Deguang 
Published: January 2021

AbstractPapillary thyroid cancer (PTC) has a continuously increasing incidence and imposes a heavy medical burden to individuals and society due to its high proportion of lymph node metastasis and recurrence in recent years. Circular RNAs, a class of noncoding RNAs, participate in the progression of many cancers, but the role of circRNAs in PTC is still rarely reported. In this study, circRNA deep sequencing was performed to identify differentially expressed circRNAs in PTC. CircRUNX1 was selected for its high expression in PTC, and circRUNX1 silencing was directly associated with the week potential for migration, invasion and proliferation of PTC in vivo and in vitro. Fluorescence in situ hybridization (FISH) was further used to confirm the cytoplasmic localization of circRUNX1, indicating the possible function of circRUNX1 as a ceRNAs in PTC progression through miRNA binding. MiR-296-3p was then confirmed to be regulated by circRUNX1 and to target DDHD domain containing 2 (DDHD2) by luciferase reporter assays. The strong antitumor effect of miR-296-3p and the tumor-promoting effect of DDHD2 were further investigated in PTC, indicating that circRUNX1 modulates PTC progression through the miR-296-3p/DDHD2 pathway. Overall, circRUNX1 plays an oncogenic role in PTC and provides a potentially effective therapeutic strategy for PTC progression.
Lymphangiogenesis in renal fibrosis arises from macrophages via VEGF-C/VEGFR3-dependent autophagy and polarization
Authors: Zhang Ying , Zhang Conghui , Li Lixi , Liang Xinjun , Cheng Peng , Li Qing , Chang Xiaoyan , Wang Kun , Huang Shuai , Li Yueqiang , Liu Yanyan , Xu Gang 
Published: January 2021

AbstractInflammation plays a crucial role in the occurrence and development of renal fibrosis, which ultimately results in end-stage renal disease (ESRD). There is new focus on lymphangiogenesis in the field of inflammation. Recent studies have revealed the association between lymphangiogenesis and renal fibrosis, but the source of lymphatic endothelial cells (LECs) is not clear. It has also been reported that macrophages are involved in lymphangiogenesis through direct and indirect mechanisms in other tissues. We hypothesized that there was a close relationship between macrophages and lymphatic endothelial progenitor cells in renal fibrosis. In this study, we demonstrated that lymphangiogenesis occurred in a renal fibrosis model and was positively correlated with the degree of fibrosis and macrophage infiltration. Compared to resting (M0) macrophages and alternatively activated (M2) macrophages, classically activated (M1) macrophages predominantly transdifferentiated into LECs in vivo and in vitro. VEGF-C further increased M1 macrophage polarization and transdifferentiation into LECs by activating VEGFR3. It was suggested that VEGF-C/VEGFR3 pathway activation downregulated macrophage autophagy and subsequently regulated macrophage phenotype. The induction of autophagy in macrophages by rapamycin decreased M1 macrophage polarization and differentiation into LECs. These results suggested that M1 macrophages promoted lymphangiogenesis and contributed to newly formed lymphatic vessels in the renal fibrosis microenvironment, and VEGF-C/VEGFR3 signaling promoted macrophage M1 polarization by suppressing macrophage autophagy and then increased the transdifferentiation of M1 macrophages into LECs.
Genomic profiles and tumor immune microenvironment of primary lung carcinoma and brain oligo-metastasis
Authors: Song Zhengbo , Yang Ling , Zhou Zhipeng , Li Pansong , Wang Wenxian , Cheng Guoping , Chen Rongrong , Chang Lianpeng , Zhang Yiping , Guan Yanfang , Xia Xuefeng , Yi Xin , Zhou Rongrong , Chen Ming 
Published: January 2021

AbstractBrain metastasis (BM) is a common malignant event in lung cancer. Here, we recruited 33 lung cancer patients with brain oligo-metastasis to explore the genomic features and tumor immune microenvironment (TIME) of the lung and BM independently. For genomic profiling, targeted sequencing was performed. We found that high-frequent ZFHX3 occurred in the lung (40%) and brain tumor (28%), which might relate to brain metastasis event; the vast majority of patients had lesions-shared mutations in primary tumor and BM, confirming the common clonal events; and EGFR was the most frequently clonal gene in both lung and BM, indicating its driver capability. To characterize TIME status, we also sequenced the T cell receptor (TCR) repertoires and performed immunohistochemistry (IHC) on CD8+ tumor-infiltrating lymphocytes (TILs) and PD-L1 expression in 28 patients who had paired samples. Through the comparison, the TCR clonality of BM was higher than lung tumor, indicating the distinct pattern of the stronger oligoclonal T cell expansion in BM; the primary tumor had a higher TMB than oligo-BM (13.9 vs 8.7 mutations, p = 0.019); CD8 + TILs of BM were significantly lower than lung tumor (10% vs 30%, p = 0.015), revealing the lower level of cytotoxic T cell infiltration; BM showed statistically equivalent level of PD-L1 compared with lung tumor (p = 0.722). We further investigated the potential biomarkers associated with overall survival (OS) after brain surgery. We found that higher TCR clonality was related to prolonged OS in EGFR-treated patients (HR 0.175, p < 0.001) but the worse outcomes in non-EGFR-treated (HR 2.623, p = 0.034). More CD8+ TILs were an independently positive indicator for OS, in EGFR-treated (HR 0.160, p = 0.001) and non-EGFR-treated patients (HR 0.308, p = 0.009). These findings provide a meaningful molecular and clinical understanding of lung carcinoma and brain oligo-metastasis.
White pupae phenotype of tephritids is caused by parallel mutations of a MFS transporter
Authors: Ward Christopher M. , Aumann Roswitha A. , Whitehead Mark A. , Nikolouli Katerina , Leveque Gary , Gouvi Georgia , Fung Elisabeth , Reiling Sarah J. , Djambazian Haig , Hughes Margaret A. , Whiteford Sam , Caceres-Barrios Carlos , Nguyen Thu N. M. , Choo Amanda , Crisp Peter , Sim Sheina B. , Geib Scott M. , Marec František , Häcker Irina , Ragoussis Jiannis , Darby Alistair C. , Bourtzis Kostas , Baxter Simon W. , Schetelig Marc F. 
Published: January 2021

AbstractMass releases of sterilized male insects, in the frame of sterile insect technique programs, have helped suppress insect pest populations since the 1950s. In the major horticultural pests Bactrocera dorsalis, Ceratitis capitata, and Zeugodacus cucurbitae, a key phenotype white pupae (wp) has been used for decades to selectively remove females before releases, yet the gene responsible remained unknown. Here, we use classical and modern genetic approaches to identify and functionally characterize causal wp− mutations in these distantly related fruit fly species. We find that the wp phenotype is produced by parallel mutations in a single, conserved gene. CRISPR/Cas9-mediated knockout of the wp gene leads to the rapid generation of white pupae strains in C. capitata and B. tryoni. The conserved phenotype and independent nature of wp− mutations suggest this technique can provide a generic approach to produce sexing strains in other major medical and agricultural insect pests.
The SARS-CoV-2 nucleocapsid phosphoprotein forms mutually exclusive condensates with RNA and the membrane-associated M protein
Authors: Lu Shan , Ye Qiaozhen , Singh Digvijay , Cao Yong , Diedrich Jolene K. , Yates John R. , Villa Elizabeth , Cleveland Don W. , Corbett Kevin D. 
Published: January 2021

AbstractThe multifunctional nucleocapsid (N) protein in SARS-CoV-2 binds the ~30 kb viral RNA genome to aid its packaging into the 80–90 nm membrane-enveloped virion. The N protein is composed of N-terminal RNA-binding and C-terminal dimerization domains that are flanked by three intrinsically disordered regions. Here we demonstrate that the N protein’s central disordered domain drives phase separation with RNA, and that phosphorylation of an adjacent serine/arginine rich region modulates the physical properties of the resulting condensates. In cells, N forms condensates that recruit the stress granule protein G3BP1, highlighting a potential role for N in G3BP1 sequestration and stress granule inhibition. The SARS-CoV-2 membrane (M) protein independently induces N protein phase separation, and three-component mixtures of N + M + RNA form condensates with mutually exclusive compartments containing N + M or N + RNA, including annular structures in which the M protein coats the outside of an N + RNA condensate. These findings support a model in which phase separation of the SARS-CoV-2 N protein contributes both to suppression of the G3BP1-dependent host immune response and to packaging genomic RNA during virion assembly.