bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Peculiar Trajectory of Global Warming
Authors: Fueglistaler S. , Silvers L.G. 
Published: January 2021

AbstractGeneral Circulation Model (GCM) simulations with prescribed observed sea surface temperature (SST) over the historical period show systematic global shortwave cloud radiative effect (SWCRE) variations uncorrelated with global surface temperature (known as “pattern effect”). Here, we show that a single parameter that quantifies the difference in SSTs between regions of tropical deep convection and the tropical or global average (Δconv) captures the time‐varying “pattern effect” in the simulations using the PCMDI/AMIPII SST recommended for CMIP6. In particular, a large positive trend in the 1980s–1990s in Δconv explains the change of sign to a strongly negative SWCRE feedback since the late 1970s. In these decades, the regions of deep convection warm about +50% more than the tropical average. Such an amplification is rarely observed in forced coupled atmosphere‐ocean GCM simulations, where the amplified warming is typically about +10%. During the post 2000 global warming hiatus Δconv shows little change, and the more recent period of resumed global warming is too short to robustly detect trends. In the prescribed SST simulations, Δconv is forced by the SST difference between warmer and colder regions. An index thereof (SST#) evaluated for six SST reconstructions shows similar trends for the satellite era, but the difference between the pre‐ and the satellite era is substantially larger in the PCMDI/AMIPII SSTs than in the other reconstructions. Quantification of the cloud feedback depends critically on small changes in the shape of the SST probability density distribution. These sensitivities underscore how essential highly accurate, persistent, and stable global climate records are to determine the cloud feedback.
Ecosystem Scale Implication of Soil CO2 Concentration Dynamics During Soil Freezing in Alaskan Arctic Tundra Ecosystems
Authors: Wilkman Eric , Zona Donatella , Arndt Kyle , Gioli Beniamino , Nakamoto Kyoko , Lipson David A. , Oechel Walter C. 
Published: January 2021

AbstractThe rates, processes, and controls on Arctic cold period soil carbon loss are still poorly understood. To understand one component of winter CO2 loss in the atmosphere, continuous measurements of soil (CO2) were made and compared to ecosystem scale CO2 fluxes. Measurements of soil (CO2) were made near Utqiaġvik, Alaska from the beginning of soil thaw in summer 2005 to spring 2007. In the summer, soil (CO2) rose with increased soil temperature, reaching value orders of magnitude higher than the atmospheric (CO2). Soil (CO2) initially decreased at the end of summer and beginning of fall but then increased subsequent to soil freezing. Due to complex changes in biological activity, storage, and transport processes, soil (CO2) was then approximately doubled than that was observed in the summer. After reaching peak concentrations in November, soil (CO2) steeply decreased over a couple of weeks, suggesting a substantial release of CO2 into the atmosphere and movement within the soil column. Eddy covariance (EC) measurements showed variable but continued emissions of CO2 to the atmosphere during freezeup. The disconnect between soil (CO2) and landscape level fluxes may be attributed to the spatiotemporal heterogeneity in release of high concentrations of soil (CO2) to the atmosphere during the fall; and when integrated over the area of the EC tower footprint, do not frequently result in detectable emission events. Continued monitoring of fall and winter soil (CO2) and ecosystem fluxes will be vital for further understanding the variability of interannual Arctic CO2 emissions.
New Insights into the Lateral‐Strength Variations and Depth to the Brittle‐Ductile Transition Zone in NW Iberia
Authors: Fernández‐Lozano J. , Martín‐González F. , De Vicente G. 
Published: January 2021

AbstractThe northwest of Iberia experiences important tectonic activity that has led to several episodes of seismic swarms. Despite substantial knowledge of the surface structures that could be responsible for this activity, their distribution at depth remains unclear. Geophysical research and rheological data display important discrepancies concerning the deep structure of the area. In order to shed light on the processes that control deep seismicity and their relationship with surface structures, we combine the analysis of seismic activity in northwest Iberia with the interpretation of sandbox experiments simulating tectonic structures similar to those observed. The structural interpretation of the modeling results was conducted by analyzing the surface particle image velocimetry field. Additionally, yield strength and brittle‐ductile transition zone (BDTZ) maps were constructed from model sections. The modeling results show a direct relationship between the main active structures developed along pre‐existing weak zones and the observed variations in crustal thickness. Moreover, these thickened zones correspond to the sectors where the BDTZ in the crust deepens. Therefore, the anomalous thickness and lateral variations of the seismogenic zone cannot be solely explained by rheological or structural changes but result from a combination of factors such as fluid pressure and the location of fractures at depth, which controls the fluid migration responsible for the failure of crustal faults. These factors can trigger seismic activity at depth and may control the observed thickness variations in the BDTZ.
Crustal Deformation and Fault Strength of the Sulawesi Subduction Zone
Authors: Greenfield T. , Copley A. C. , Caplan C. , Supendi P. , Widiyantoro S. , Rawlinson N. 
Published: January 2021

AbstractThis paper investigates the seismicity and rheology of the North‐Sulawesi subduction zone. Body‐wave modeling is used to estimate focal mechanisms and centroid depths of moderate magnitude (M5–M6.5) earthquakes on the North Sulawesi megathrust and surrounding region. The slip vectors of megathrust earthquakes radiate outward from Sulawesi, indicating motion that is incompatible with the relative motion of two rigid plates. Instead, the observed deformation implies lateral spreading of high topography, controlled by gravitational potential energy contrasts. This finding suggests that the observed deformation of Sulawesi results from stresses transmitted through the lithosphere, rather than basal tractions due to circulation in the mantle. Our modeling of the force balance on the megathrust shows that the subduction megathrust is weak, with an average shear stress of ∼13 MPa and an effective coefficient of friction of 0.03. Elsewhere in Sulawesi, slip vectors of other earthquakes suggest similar potential‐energy‐driven deformation is present, but at significantly slower rates. Our results show the importance of lateral rheology contrasts in determining deformation rate, and hence seismic hazard, in response to a given driving force.
A novel hypoxic long noncoding RNA KB-1980E6.3 maintains breast cancer stem cell stemness via interacting with IGF2BP1 to facilitate c-Myc mRNA stability
Authors: Zhu Pengpeng , He Fang , Hou Yixuan , Tu Gang , Li Qiao , Jin Ting , Zeng Huan , Qin Yilu , Wan Xueying , Qiao Yina , Qiu Yuxiang , Teng Yong , Liu Manran 
Published: January 2021

AbstractThe hostile hypoxic microenvironment takes primary responsibility for the rapid expansion of breast cancer tumors. However, the underlying mechanism is not fully understood. Here, using RNA sequencing (RNA-seq) analysis, we identified a hypoxia-induced long noncoding RNA (lncRNA) KB-1980E6.3, which is aberrantly upregulated in clinical breast cancer tissues and closely correlated with poor prognosis of breast cancer patients. The enhanced lncRNA KB-1980E6.3 facilitates breast cancer stem cells (BCSCs) self-renewal and tumorigenesis under hypoxic microenvironment both in vitro and in vivo. Mechanistically, lncRNA KB-1980E6.3 recruited insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) to form a lncRNA KB-1980E6.3/IGF2BP1/c-Myc signaling axis that retained the stability of c-Myc mRNA through increasing binding of IGF2BP1 with m6A-modified c-Myc coding region instability determinant (CRD) mRNA. In conclusion, we confirm that lncRNA KB-1980E6.3 maintains the stemness of BCSCs through lncRNA KB-1980E6.3/IGF2BP1/c-Myc axis and suggest that disrupting this axis might provide a new therapeutic target for refractory hypoxic tumors.
A genomic view of the microbiome of coral reef demosponges
Authors: Robbins S J , Song W , Engelberts J P , Glasl B , Slaby B M , Boyd J , Marangon E , Botté E S , Laffy P , Thomas T , Webster N S 
Published: January 2021

Abstract
Sponges underpin the productivity of coral reefs, yet few of their microbial symbionts have been functionally characterised. Here we present an analysis of ~1200 metagenome-assembled genomes (MAGs) spanning seven sponge species and 25 microbial phyla. Compared to MAGs derived from reef seawater, sponge-associated MAGs were enriched in glycosyl hydrolases targeting components of sponge tissue, coral mucus and macroalgae, revealing a critical role for sponge symbionts in cycling reef organic matter. Further, visualisation of the distribution of these genes amongst symbiont taxa uncovered functional guilds for reef organic matter degradation. Genes for the utilisation of sialic acids and glycosaminoglycans present in sponge tissue were found in specific microbial lineages that also encoded genes for attachment to sponge-derived fibronectins and cadherins, suggesting these lineages can utilise specific structural elements of sponge tissue. Further, genes encoding CRISPR and restriction-modification systems used in defence against mobile genetic elements were enriched in sponge symbionts, along with eukaryote-like gene motifs thought to be involved in maintaining host association. Finally, we provide evidence that many of these sponge-enriched genes are laterally transferred between microbial taxa, suggesting they confer a selective advantage within the sponge niche and therefore play a critical role in host ecology and evolution.
Eight years of experience with vismodegib for advanced and multiple basal cell carcinoma patients in the Netherlands: a retrospective cohort study
Authors: Verkouteren Babette J. A. , Wakkee Marlies , Reyners An K. L. , Nelemans Patty , Aarts Maureen J. B. , Rácz Emőke , Terra Jorrit B. , Devriese Lot A. , Alers Robert-Jan , Kapiteijn Ellen , van Doorn Remco , Bekkenk Marcel W. , Reinders Marie G.H.C. , Mosterd Klara 
Published: January 2021

Abstract
Background
Vismodegib has been used for the treatment of locally advanced basal cell carcinoma (laBCC) and metastatic BCC (mBCC) since 2011. Most efficacy and safety data are provided by clinical trials. This study evaluates the effectiveness of vismodegib for the treatment of laBCC, mBCC and basal cell nevus syndrome (BCNS) patients, and the tumour characteristics associated with a higher probability of achieving a complete response in the Netherlands.

Methods
A retrospective cohort study that included all patients ≥18 years with histologically proven basal cell carcinoma that received ≥1 dose of vismodegib between July 2011 and September 2019 in the Netherlands.

Results
In total, 48 laBCC, 11 mBCC and 19 BCNS patients were included. Median progression-free survival was 10.3 months (95% confidence interval (CI), 7.5–22.6) for laBCC, 11.7 (95% CI, 5.2–17.5) for mBCC and 19.1 (95% CI, 7.4–20.2) for BCNS. Larger laBCCs were associated with a lower probability of complete response (hazard ratio (HR) 0.77 per increase in cm, p = 0.02). Of all BCNS patients, 63% received ≥2 treatment sequences with vismodegib; all achieved partial responses.

Conclusions
Half of the aBCC patients progress within 1 year after the start of vismodegib treatment. More research is needed to investigate other treatment strategies after vismodegib progression and to evaluate long-term effects of repetitive vismodegib treatment.
Diagnostic performance of a faecal immunochemical test for patients with low-risk symptoms of colorectal cancer in primary care: an evaluation in the South West of England
Authors: Bailey Sarah E. R. , Abel Gary A. , Atkins Alex , Byford Rachel , Davies Sarah-Jane , Mays Joe , McDonald Timothy J. , Miller Jon , Neck Catherine , Renninson John , Thomas Paul , Walter Fiona M. , Warren Sarah , Hamilton Willie 
Published: January 2021

Abstract
Background
The faecal immunochemical test (FIT) was introduced to triage patients with low-risk symptoms of possible colorectal cancer in English primary care in 2017, underpinned by little primary care evidence.

Methods
All healthcare providers in the South West of England (population 4 million) participated in this evaluation. 3890 patients aged ≥50 years presenting in primary care with low-risk symptoms of colorectal cancer had a FIT from 01/06/2018 to 31/12/2018. A threshold of 10 μg Hb/g faeces defined a positive test.

Results
Six hundred and eighteen (15.9%) patients tested positive; 458 (74.1%) had an urgent referral to specialist lower gastrointestinal (GI) services within three months. Forty-three were diagnosed with colorectal cancer within 12 months. 3272 tested negative; 324 (9.9%) had an urgent referral within three months. Eight were diagnosed with colorectal cancer within 12 months. Positive predictive value was 7.0% (95% CI 5.1–9.3%). Negative predictive value was 99.8% (CI 99.5–99.9%). Sensitivity was 84.3% (CI 71.4–93.0%), specificity 85.0% (CI 83.8–86.1%). The area under the ROC curve was 0.92 (CI 0.86–0.96). A threshold of 37 μg Hb/g faeces would identify patients with an individual 3% risk of cancer.

Conclusions
FIT performs exceptionally well to triage patients with low-risk symptoms of colorectal cancer in primary care; a higher threshold may be appropriate in the wake of the COVID-19 crisis.
Overcoming the challenges associated with CD3+ T-cell redirection in cancer
Authors: Singh Ajit , Dees Sundee , Grewal Iqbal S. 
Published: January 2021

AbstractThe development of bispecific antibodies that redirect the cytotoxic activity of CD3+ T cells to tumours is a promising immunotherapeutic strategy for the treatment of haematological malignancies and solid cancers. Since the landmark FDA approval at the end of 2014 of the anti-CD3 × anti-CD19 bispecific antibody blinatumomab (Blincyto®) for the treatment of relapsed/refractory B-cell acute lymphoblastic leukaemia, ~100 clinical trials investigating the safety and efficacy of CD3+ bispecific T-cell redirectors for cancer have been initiated. However, despite early success, numerous challenges pertaining to CD3+ T-cell redirection in the context of cancer exist, including the recruitment of counterproductive CD3+ T-cell subsets, the release of systemic cytokines, the expansion of immune checkpoint molecules, the presence of an immunosuppressive tumour microenvironment, tumour antigen loss/escape, on-target off-tumour toxicity and suboptimal potency. The aim of the present review is to discuss novel approaches to overcome the key challenges associated with CD3+ bispecific T-cell redirection in order to achieve an optimal balance of anti-tumour activity and safety.
Changes in retinal microvasculature and retinal layer thickness in association with apolipoprotein E genotype in Alzheimer’s disease
Authors: Shin Joo Youn , Choi Eun Young , Kim Min , Lee Hyung Keun , Byeon Suk Ho 
Published: January 2021

AbstractBiomarker tests of Alzheimer’s disease (AD) are invasive and expensive. Recent developments in optical coherence tomography (OCT) and OCT angiography (OCTA) have enabled noninvasive, cost-effective characterization of retinal layer vasculature and thickness. Using OCTA and OCT, we characterized retinal microvascular changes in the mild cognitive impairment (MCI) stage of AD and assessed their correlation with structural changes in each retinal neuronal layer. We also evaluated the effect of the APOE-ε4 genotype on retinal microvasculature and layer thickness. Retinal layer thickness did not differ between MCI patients (40 eyes) and controls (37 eyes, all p > 0.05). MCI patients had lower vessel density (VD) (p = 0.003) of the superficial capillary plexus (SCP) and larger foveal avascular zone area (p = 0.01) of the deep capillary plexus (DCP) than those of controls. VD of the SCP correlated with the ganglion cell layer (r = 0.358, p = 0.03) and inner plexiform layer thickness (r = 0.437, p = 0.007) in MCI patients. APOE-ε4-carrying MCI patients had a lower VD of the DCP than non-carriers (p = 0.03). In conclusion, retinal microvasculature was reduced in patients with AD-associated MCI, but retinal thickness was not changed; these changes might be affected by the APOE genotype. OCTA of the retinal microvasculature may be useful to detect vascular changes in AD.
Pannexin 3 regulates skin development via Epiprofin
Authors: Zhang Peipei , Ishikawa Masaki , Doyle Andrew , Nakamura Takashi , He Bing , Yamada Yoshihiko 
Published: January 2021

AbstractPannexin 3 (Panx3), a member of the gap junction pannexin family is required for the development of hard tissues including bone, cartilage and teeth. However, the role of Panx3 in skin development remains unclear. Here, we demonstrate that Panx3 regulates skin development by modulating the transcription factor, Epiprofin (Epfn). Panx3−/− mice have impaired skin development and delayed hair follicle regeneration. Loss of Panx3 in knockout mice and suppression by shRNA both elicited a reduction of Epfn expression in the epidermis. In cell culture, Panx3 overexpression promoted HaCaT cell differentiation, cell cycle exit and enhanced Epfn expression. Epfn−/− mice and inhibition of Epfn by siRNA showed no obvious differences of Panx3 expression. Furthermore, Panx3 promotes Akt/NFAT signaling pathway in keratinocyte differentiation by both Panx3 ATP releasing channel and ER Ca2+ channel functions. Our results reveal that Panx3 has a key role factor for the skin development by regulating Epfn.
Genetic manipulation of pathogenic Leptospira: CRISPR interference (CRISPRi)-mediated gene silencing and rapid mutant recovery at 37 °C
Authors: Fernandes L. G. V. , Hornsby R. L. , Nascimento A. L. T. O. , Nally J. E. 
Published: January 2021

AbstractLeptospirosis is a neglected, widespread zoonosis caused by pathogenic species of the genus Leptospira, and is responsible for 60,000 deaths per year. Pathogenic mechanisms of leptospirosis remain poorly understood mainly because targeted mutations or gene silencing in pathogenic Leptospira continues to be inherently inefficient, laborious, costly and difficult to implement. In addition, pathogenic leptospires are highly fastidious and the selection of mutants on solid agar media can take up to 6 weeks. The catalytically inactive Cas9 (dCas9) is an RNA-guided DNA-binding protein from the Streptococcus pyogenes CRISPR/Cas system and can be used for gene silencing, in a strategy termed CRISPR interference (CRISPRi). Here, this technique was employed to silence genes encoding major outer membrane proteins of pathogenic L. interrogans. Conjugation protocols were optimized using the newly described HAN media modified for rapid mutant recovery at 37 °C in 3% CO2 within 8 days. Complete silencing of LipL32 and concomitant and complete silencing of both LigA and LigB outer membrane proteins were achieved, revealing for the first time that Lig proteins are involved in pathogenic Leptospira serum resistance. Gene silencing in pathogenic leptospires and rapid mutant recovery will facilitate novel studies to further evaluate and understand pathogenic mechanisms of leptospirosis.
English hospital episode data analysis (1998–2018) reveal that the rise in dog bite hospital admissions is driven by adult cases
Authors: Tulloch John S. P. , Owczarczak-Garstecka Sara C. , Fleming Kate M. , Vivancos Roberto , Westgarth Carri 
Published: January 2021

AbstractDog bites are a global health issue that can lead to severe health outcomes. This study aims to describe the incidence and sociodemographics of patients admitted to English National Health Service (NHS) hospitals for dog bites (1998–2018), and to estimate their annual direct health care costs. An analysis of patient level data utilising hospital episode statistics for NHS England, including: temporal trends in annual incidence of admission, Poisson models of the sociodemographic characteristics of admitted patients, and direct health care cost estimates. The incidence of dog bite admissions rose from 6.34 (95%CI 6.12–6.56) in 1998 to 14.99 (95%CI 14.67–15.31) admissions per 100,000 population in 2018, with large geographic variation. The increase was driven by a tripling of incidence in adults. Males had the highest rates of admission in childhood. Females had two peaks in admission, childhood and 35–64 years old. Two percent (2.05%, 95%CI 0.93–3.17) of emergency department attendances resulted in admission. Direct health care costs increased and peaked in the financial year 2017/2018 (admission costs: £25.1 million, emergency attendance costs: £45.7million). Dog bite related hospital admissions have increased solely in adults. Further work exploring human–dog interactions, stratified by demographic factors, is urgently needed to enable the development of appropriate risk reduction intervention strategies.
The Promise of Comprehensive Early Reading Instruction for Children With Autism and Recommendations for Future Directions
Authors: Arciuli Joanne , Bailey Benjamin 
Published: January 2021

PurposeChildren with autism have an increased likelihood of reading difficulties. The reasons for this are numerous and varied, but many children with autism can learn to read when they are provided with evidence-based early reading instruction.MethodHere, we provide an overview of some of the factors that impact early reading development for children with autism and a rationale for the provision of comprehensive early reading instruction consistent with the recommendations of the National Reading Panel (NRP). We discuss research on NRP instruction for children with autism, including some of our own empirical studies. We also discuss some areas of research that were not emphasized by the NRP but that we view as important. We offer recommendations that extend beyond NRP guidelines in order to advance knowledge and improve practice.ConclusionsComprehensive early reading instruction holds great promise for children with autism, but there are gaps in our understanding that need to be addressed. These include the most effective method(s) for tailoring reading instruction to the needs of the individual while optimizing delivery to small groups of children, supporting skills and making other accommodations not outlined by the NRP, and consideration of bilingualism and of reading instruction in languages other than English, among other issues. While our focus in this review article is early reading instruction for children with autism who use oral language, we acknowledge that there is a major gap in the literature concerning reading instruction for those who do not use oral language. We hope that this review article will be helpful to clinicians, educators, and researchers alike, as well as children with autism and their families, friends, and support networks.