bluuebunny/crossref_metadata_2025_split huggingface dataset:
Innovations in Pediatric Therapeutics Development: Principles for the Use of Bridging Biomarkers in Pediatric Extrapolation
Authors: Fleming Thomas R. , Garnett Christine E. , Conklin Laurie S. , Corriol-Rohou Solange , Hariharan Sudharshan , Hsu Daphne , Mueller-Velten Guenther , Mulugeta Yeruk , Portman Ronald , Rothmann Mark D. , Stockbridge Norman L. , Wandel Simon , Zhang Jialu , Yao Lynne 
Published: September 2022

AbstractEven with recent substantive improvements in health care in pediatric populations, considerable need remains for additional safe and effective interventions for the prevention and treatment of diseases in children. The approval of prescription drugs and biological products for use in pediatric settings, as in adults, requires demonstration of substantial evidence of effectiveness and favorable benefit-to-risk. For diseases primarily affecting children, such evidence predominantly would be obtained in the pediatric setting. However, for conditions affecting both adults and children, pediatric extrapolation uses scientific evidence in adults to enable more efficiently obtaining a reliable evaluation of an intervention’s effects in pediatric populations. Bridging biomarkers potentially have an integral role in pediatric extrapolation. In a setting where an intervention reliably has been established to be safe and effective in adults, and where there is substantive evidence that disease processes in pediatric and adult settings are biologically similar, a ‘bridging biomarker’ should satisfy three additional criteria: effects on the bridging biomarker should capture effects on the principal causal pathway through which the disease process meaningfully influences ‘feels, functions, survives’ measures; secondly, the experimental intervention should not have important unintended effects on ‘feels, functions, survives’ measures not captured by the bridging biomarker; and thirdly, in statistical analyses in adults, the intervention’s net effect on ‘feels, functions, survives’ measures should be consistent with what would be predicted by its level of effect on the bridging biomarker. A validated bridging biomarker has considerable potential utility, since an intervention’s efficacy could be extrapolated from adult to pediatric populations if evidence in children establishes the intervention not only to be safe but also to have substantive effects on that bridging biomarker. Proper use of bridging biomarkers could increase availability of reliably evaluated therapies approved for use in pediatric settings, enabling children and their caregivers to make informed choices about health care.
Direct Multi‐Modal Inversion of Geophysical Logs Using Deep Learning
Authors: Alyaev Sergey , Elsheikh Ahmed H. 
Published: September 2022

AbstractGeosteering of wells requires fast interpretation of geophysical logs which is a non‐unique inverse problem. Current work presents a proof‐of‐concept approach to multi‐modal probabilistic inversion of logs using a single evaluation of an artificial deep neural network (DNN). A mixture density DNN (MDN) is trained using the ”multiple‐trajectory‐prediction” loss functions, which avoids mode collapse typical for traditional MDNs, and allows multi‐modal prediction ahead of data. The proposed approach is verified on the real‐time stratigraphic inversion of gamma‐ray logs. The multi‐modal predictor outputs several likely inverse solutions/predictions, providing more accurate and realistic solutions compared to a deterministic regression using a DNN. For these likely stratigraphic curves, the model simultaneously predicts their probabilities, which are implicitly learned from the training geological data. The stratigraphy predictions and their probabilities obtained in milliseconds from the MDN can enable better real‐time decisions under geological uncertainties.
Estimation of On‐Road PM2.5 Distributions by Combining Satellite Top‐of‐Atmosphere With Microscale Geographic Predictors for Healthy Route Planning
Authors: Tong Chengzhuo , Shi Zhicheng , Shi Wenzhong , Zhang Anshu 
Published: September 2022

AbstractHow to reduce the health risks for commuters, caused by air pollution such as PM2.5 has always been an urgent issue needing to be solved. Proposed in this study, is a novel framework which enables greater avoidance of pollution and hence assists the provision of healthy travel. This framework is based on the estimation of on‐road PM2.5 throughout the whole city. First, the micro‐scale PM2.5 is predicted by land use regression (LUR) modeling enhanced by the use of the Landsat‐8 top‐of‐atmosphere (TOA) data and microscale geographic predictors. In particular, the green view index (GVI) factor derived, the sky view factor, and the index‐based built‐up index, are incorporated within the TOA‐LUR modeling. On‐road PM2.5 distributions are then mapped in high‐spatial‐resolution. The maps obtained can be used to find healthy travel routes with less PM2.5. The proposed framework was applied in high‐density Hong Kong by Landsat 8 images. External testing was based on mobile measurements. The results showed that the estimation performance of the proposed seasonal TOA‐LUR Geographical and Temporal Weighted Regression models is at a high‐level with an R2 of 0.70–0.90. The newly introduced GVI index played an important role in these estimations. The PM2.5 distribution maps at high‐spatial‐resolution were then used to develop an application providing Hong Kong residents with healthy route planning services. The proposed framework can, likewise, be applied in other cities to better ensure people's health when traveling, especially those in high‐density cities.
High‐Resolution Imaging of Fault Zone Structure Along the Creeping Section of the Haiyuan Fault, NE Tibet, From Data Recorded by Dense Seismic Arrays
Authors: Zhang Zhou , Deng Yangfan , Qiu Hongrui , Peng Zhigang , Liu‐Zeng Jing 
Published: September 2022

AbstractHigh‐resolution imaging of fault zone structures is essential for understanding earthquake physics and fault mechanics. As a major left‐lateral strike‐slip fault in northeastern Tibet, fine structures of the damage zone in the creeping (Laohushan) section of the Haiyuan fault remain unclear. To resolve geometry and velocity reduction of the damage zone, we deployed a dense temporary network of 110 seismic stations around the creeping section of the Haiyuan fault. Travel time delays from teleseismic P arrivals suggest an approximately 1‐km‐wide low‐velocity zone, likely illuminating a broader damage zone around the Haiyuan fault. A catalog is constructed for local earthquakes based on phase picks identified from a machine learning technique. The amplification of waveforms from these local events and waveform modeling of fault zone trapped waves indicate a narrower inner damage zone with depth‐dependent width (ranging from 150 to 50 m) that extends to a depth of approximately 4 km. These values are generally consistent with those found on other noncreeping faults in California, suggesting that these damage zone properties are not affected by fault slip behaviors at shallow depth. In addition, a clear bi‐material velocity contrast across the fault is revealed by the analysis of teleseismic P arrivals. Assuming the contrast extends to a depth of 15 km, we find that P‐wave velocity is approximately 5% slower in the crustal block north of the fault. Our study shows that a temporary dense seismic network is effective in illuminating cross‐fault velocity contrast and fault geometry.
Shallow Crustal Response to Arabia‐Eurasia Convergence in Northwestern Iran: Constraints From Multifrequency P‐Wave Receiver Functions
Authors: Wang Xu , Chen Ling , Talebian Morteza , Ai Yinshuang , Jiang Mingming , Yao Huajian , He Yumei , Ghods Abdolreza , Sobouti Farhad , Wan Bo , Chu Yang , Hou Guangbing , Chen Qi‐Fu , Chung Sun‐Lin , Xiao Wenjiao , Wu Fu‐Yuan , Zhu Rixiang 
Published: September 2022

AbstractThe Neo‐Tethys subduction and subsequent Arabia‐Eurasia continental collision invoked widespread Cenozoic tectono‐magmatism throughout the Iranian Plateau. We herein develop a new method to image the shallow crustal S‐wave velocity (Vs) structure by joint inversion of multifrequency waveforms and horizontal‐to‐vertical ratios around the direct P phase in P‐wave receiver functions. Synthetic tests demonstrate the validity of our method in constraining the absolute Vs values beneath single stations down to ∼12‐km depth. By applying this method to a seismic array of 63 stations with an average spacing of ∼10 km along the main profile, we construct a detailed shallow crustal Vs model across the northwestern Iranian Plateau. The model is characterized by distinct high‐ and low‐velocity anomalies beneath the Iranian hinterland and the Zagros foreland fold‐and‐thrust belt, respectively. In combination with geological observations and laboratory data, the imaged high‐velocity anomalies (with Vs of 3.2–3.9 km/s) may denote arc to intraplate magmatism beneath Central Iran and Alborz to the north, whereas the low‐velocity anomalies (with Vs of ∼1.65 km/s) probably represent the marl/shale layers in Late Cretaceous and Paleocene beneath Zagros. The magmatic rocks at the Iranian hinterland exhibit strong variations in absolute Vs, reflecting different bulk compositions with more mafic inland. The shale/marl layers could have acted as décollements to accommodate crustal deformation. Our observations underline both the key role of lithology‐controlled layering in sedimentary deformation at the Zagros fold‐and‐thrust belt and the change in compositions and forming‐environments of magmatic rocks at the Iranian hinterland.
Changes in Early Summer Precipitation Characteristics Over South China and Taiwan: CESM2‐LE and CMIP6 Multi‐Model Simulations and Projections
Authors: Huang Wan‐Ru , Liu Pin‐Yi , Lee Shih‐Yu , Wu Chi‐Hua 
Published: September 2022

AbstractThe May and June precipitation (known as early summer precipitation; ESP) is an important water resource for South China and Taiwan (SCTW). This study explores the similarities and differences between the Community Earth System Model Version 2‐Large Ensemble (CESM2‐LE) and the Coupled Model Intercomparison Project Phase 6 (CMIP6) multi‐model ensemble in simulating the characteristics of ESP over SCTW in the present day, and in projecting the related changes at the end of 21st century. For the present‐day simulation, our results showed that CESM2‐LE and CMIP6 outperformed each other for different examined features. CESM2‐LE was slightly better than CMIP6 in capturing the magnitude of ESP over SCTW, while CMIP6 was more capable of representing the interdecadal shifts in the occurrence timing of the ESP maximum. Both the CESM2‐LE and CMIP6 projections indicated that ESP will be enhanced and the phase of maximum ESP will be delayed, from peaking around mid‐June in the present to late June in the future. These changes can be attributed to an enhanced short‐wave trough over southwest China and a late intensification of the southwesterly wind ahead of the short‐wave trough, which help transport more moisture from the north of the South China Sea to SCTW, particularly in mid‐to‐late June. In addition, relative to CMIP6, CESM2‐LE showed less uncertainty in the projected increase in ESP and phase delay. This finding highlights that model diversity may play a more important role than internal variability in attributing the uncertainty of projected changes in ESP over SCTW.
Martian Atmospheric Spectral End‐Members Retrieval From ExoMars Thermal Infrared (TIRVIM) Data
Authors: Alemanno G. , D’Amore M. , Maturilli A. , Helbert J. , Arnold G. , Korablev O. , Ignatiev N. , Grigoriev A. , Shakun A. , Trokhimovskiy A. 
Published: September 2022

AbstractKey knowledge about planetary composition can be recovered from the study of thermal infrared spectral range datasets. This range has a huge diagnostic potential because it contains diagnostic absorptions from a planetary surface and atmosphere. The main goal of this study is to process and interpret the dataset from the Thermal Infrared channel (TIRVIM) which is part of the Atmospheric Chemistry Suite of the ExoMars2016 Trace Gas Orbiter mission to find and characterize dust and water ice clouds in the atmosphere. The method employed here is based on the application of principal component analysis and target transformation techniques to extract the independent variable components present in the analyzed dataset. Spectral shapes of both atmospheric dust and water ice aerosols have been recovered from the analysis of TIRVIM data. The comparison between our results with those previously obtained on Thermal Emission Spectrometer (TES) data and with previous analysis on TIRVIM data, validates the methodology here applied, showing that it allows to correctly recover the atmospheric spectral endmembers present in the TIRVIM data. Moreover, comparison with atmospheric retrievals on PFS, TES and IRIS data, allowed us to assess the temporal stability and homogeneity of dust and water ice components in the Martian atmosphere over a time period of almost 50 years.
Glass Ionomer Cement as a preventative fissure sealant for first permanent molars in high caries risk patients waiting general anaesthetic—a case series
Authors: Mummery Toby Andrew , Popat Riddhi 
Published: September 2022

Abstract
Objective/aim
The aim of this case series was to assess the ongoing suitability of Glass Ionomer Cement Fissure Sealants for use in paediatric patients. These had been used through the COVID pandemic due to their status as a non-aerosol-generating procedure.

Materials and methods
A retrospective clinical review was undertaken to identify cases where GIC Fissure Sealants were used in paediatric patients awaiting exodontia general anaesthetic within Harrogate and District NHS Foundation Trust Community Dental Service. Identified cases were then collated to form this case series. These were reviewed regarding the number of GIC fissure sealants placed, and retention at the GA appointment and any subsequent follow-up appointments.

Results
The results showed favourable results of GIC fissure sealants, with an average retention of 77% – in line with the wider literature results for GIC fissure sealants.

Discussion
The results showed a favourable retention rate, particularly given patient challenges leading to them requiring exodontia GA. Review of alternative fissure sealant materials may be beneficial on a local level to compare results with the available literature and confirm ongoing suitability.

Conclusions
The results appear to support the ongoing use of GIC-FS where close patient monitoring is available.
Ischemia and reperfusion injury combined with cisplatin induces immunogenic cell death in lung cancer cells
Authors: Zhang Shuai , Li Yumei , Liu Shuqing , Ma Pei , Guo Mengfei , Zhou E. , Duan Limin , Fan Jinshuo , Liao Tingting , Tan Qi , Wang Xuan , Wu Feng , Jin Yang 
Published: September 2022

AbstractA first-line chemotherapeutic drug for non-small cell lung cancer (NSCLC), cisplatin (CDDP), fails to induce immunogenic cell death (ICD) because it fails to induce calreticulin (CRT) exposure on the cell surface. We investigated the potential of ischemia and reperfusion injury (I/R) combined with CDDP to induce ICD in lung cancer cells. The in vitro model of I/R, oxygen-glucose deprivation and reperfusion (OGD/R), effectively induced CRT exposure, ATP secretion, high mobility group box 1 (HMGB1) release and eIF2α phosphorylation in both Lewis lung carcinoma (LLC) and A549 cells when combined with CDDP. By using a vaccine assay and coculture with bone marrow-derived dendritic cells (BMDCs), we showed that OGD/R restored the immunogenicity of CDDP by phosphorylating eIF2α and demonstrated that OGD/R + CDDP (O + C) is an ICD inducer. Using the inguinal tumor model, we found that I/R significantly enhanced the tumor-killing effect of CDDP and Mitomycin C, and this effect relied on adaptive antitumor immunity. Consistently, I + C altered the ratio of interferon-gamma-secreting T lymphocytes, thus overcoming the immunosuppressive effect induced by CDDP. In conclusion, our research presents a new combination strategy and indicates that I/R is a potential anticancer immunogenic modality when combined with nonimmunogenic chemotherapy.
ROBO3s: a novel ROBO3 short isoform promoting breast cancer aggressiveness
Authors: Werner Marcel , Dyas Anna , Parfentev Iwan , Schmidt Geske E. , Mieczkowska Iga K. , Müller-Kirschbaum Lukas C. , Müller Claudia , Kalkhof Stefan , Reinhardt Oliver , Urlaub Henning , Alves Frauke , Gallwas Julia , Prokakis Evangelos , Wegwitz Florian 
Published: September 2022

AbstractBasal-like breast cancer (BLBC) is a highly aggressive breast cancer subtype frequently associated with poor prognosis. Due to the scarcity of targeted treatment options, conventional cytotoxic chemotherapies frequently remain the standard of care. Unfortunately, their efficacy is limited as BLBC malignancies rapidly develop resistant phenotypes. Using transcriptomic and proteomic approaches in human and murine BLBC cells, we aimed to elucidate the molecular mechanisms underlying the acquisition of aggressive and chemotherapy-resistant phenotypes in these mammary tumors. Specifically, we identified and characterized a novel short isoform of Roundabout Guidance Receptor 3 (ROBO3s), upregulated in BLBC in response to chemotherapy and encoding for a protein variant lacking the transmembrane domain. We established an important role for the ROBO3s isoform, mediating cancer stem cell properties by stimulating the Hippo-YAP signaling pathway, and thus driving resistance of BLBC cells to cytotoxic drugs. By uncovering the conservation of ROBO3s expression across multiple cancer types, as well as its association with reduced BLBC-patient survival, we emphasize its potential as a prognostic marker and identify a novel attractive target for anti-cancer drug development.
FOXD1 facilitates pancreatic cancer cell proliferation, invasion, and metastasis by regulating GLUT1-mediated aerobic glycolysis
Authors: Cai Kun , Chen Shiyu , Zhu Changhao , Li Lin , Yu Chao , He Zhiwei , Sun Chengyi 
Published: September 2022

AbstractAlthough FOXD1 has been found to be involved in the malignant processes of several types of cancers, its role in pancreatic cancer (PC) is not well understood. This study aimed to investigate the expression and function of FOXD1 in PC. We found that FOXD1 mRNA and protein expression were upregulated in PC tissues compared with non-tumor tissues, and high expression level of FOXD1 was associated with an adverse prognostic index of PC. The results of in vitro and in vivo assays indicate that overexpression of FOXD1 promotes aerobic glycolysis and the capacity of PC cells to proliferate, invade, and metastasize, whereas FOXD1 knockdown inhibits these functions. The results of mechanistic experiments suggest that FOXD1 can not only directly promote SLC2A1 transcription but also inhibit the degradation of SLC2A1 through the RNA-induced silencing complex. As a result, FOXD1 enhances GLUT1 expression and ultimately facilitates PC cell proliferation, invasion, and metastasis by regulating aerobic glycolysis. Taken together, FOXD1 is suggested to be a potential therapeutic target for PC.
A multi-centre prospective evaluation of THEIA™ to detect diabetic retinopathy (DR) and diabetic macular oedema (DMO) in the New Zealand screening program
Authors: Vaghefi Ehsan , Yang Song , Xie Li , Han David , Yap Aaron , Schmeidel Ole , Marshall John , Squirrell David 
Published: September 2022

Abstract
Purpose
To validate the potential application of THEIA™ as clinical decision making assistant in a national screening program.

Methods
A total of 900 patients were recruited from either an urban large eye hospital, or a semi-rural optometrist led screening provider, as they were attending their appointment as part of New Zealand Diabetic Eye Screening Programme. The de-identified images were independently graded by three senior specialists, and final results were aggregated using New Zealand grading scheme, which was then converted to referable/non-referable and Healthy/mild/more than mild/sight threatening categories.

Results
THEIA™ managed to grade all images obtained during the study. Comparing the adjudicated images from the specialist grading team, “ground truth”, with the grading by the AI platform in detecting “sight threatening” disease, at the patient level THEIA™ achieved 100% imageability, 100% [98.49–100.00%] sensitivity and [97.02–99.16%] specificity, and negative predictive value of 100%. In other words, THEIA™ did not miss any patients with “more than mild” or “sight threatening” disease. The level of agreement between the clinicians and the aggregated results was (k value: 0.9881, 0.9557, and 0.9175), and the level of agreement between THEIA™ and the aggregated labels was (k value: 0.9515).

Conclusion
This multi-centre prospective trial showed that THEIA™ did not miss referable disease when screening for diabetic retinopathy and maculopathy. It also had a very high level of granularity in reporting the disease level. As THEIA™ has been tested on a variety of cameras, operating in a range of clinics (rural/urban, ophthalmologist-led\optometrist-led), we believe that it will be a suitable addition to a public diabetic screening program.
Observation of formation and local structures of metal-organic layers via complementary electron microscopy techniques
Authors: Peng Xinxing , Pelz Philipp M. , Zhang Qiubo , Chen Peican , Cao Lingyun , Zhang Yaqian , Liao Hong-Gang , Zheng Haimei , Wang Cheng , Sun Shi-Gang , Scott Mary C. 
Published: September 2022

AbstractMetal-organic layers (MOLs) are highly attractive for application in catalysis, separation, sensing and biomedicine, owing to their tunable framework structure. However, it is challenging to obtain comprehensive information about the formation and local structures of MOLs using standard electron microscopy methods due to serious damage under electron beam irradiation. Here, we investigate the growth processes and local structures of MOLs utilizing a combination of liquid-phase transmission electron microscopy, cryogenic electron microscopy and electron ptychography. Our results show a multistep formation process, where precursor clusters first form in solution, then they are complexed with ligands to form non-crystalline solids, followed by the arrangement of the cluster-ligand complex into crystalline sheets, with additional possible growth by the addition of clusters to surface edges. Moreover, high-resolution imaging allows us to identify missing clusters, dislocations, loop and flat surface terminations and ligand connectors in the MOLs. Our observations provide insights into controllable MOL crystal morphology, defect engineering, and surface modification, thus assisting novel MOL design and synthesis.
Cell type-specific calcium imaging of central sensitization in mouse dorsal horn
Authors: Warwick Charles , Salsovic Joseph , Hachisuka Junichi , Smith Kelly M. , Sheahan Tayler D. , Chen Haichao , Ibinson James , Koerber H. Richard , Ross Sarah E. 
Published: September 2022

AbstractAllodynia is a state in which pain is elicited by innocuous stimuli. Capsaicin applied to the skin results in an allodynia that extends to a broad region beyond the application site. This sensitization is thought to be mediated by spinal networks; however, we do not have a clear picture of which spinal neurons mediate this phenomenon. To address this gap, we used two-photon calcium imaging of excitatory interneurons and spinal projection neurons in the mouse spinal dorsal horn. To distinguish among neuronal subtypes, we developed CICADA, a cell profiling approach to identify cell types during calcium imaging. We then identified capsaicin-responsive and capsaicin-sensitized neuronal populations. Capsaicin-sensitized neurons showed emergent responses to innocuous input and increased receptive field sizes consistent with psychophysical reports. Finally, we identified spinal output neurons that showed enhanced responses from innocuous input. These experiments provide a population-level view of central sensitization and a framework with which to model somatosensory integration in the dorsal horn.