bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rock Slope Temperature Evolution and Micrometer‐Scale Deformation at a Retreating Glacier Margin
Authors: Hugentobler Marc , Aaron Jordan , Loew Simon 
Published: October 2021

AbstractIn deglaciating environments, rock mass weakening and potential formation of rock slope instabilities is driven by long‐term and seasonal changes in thermal‐ and hydraulic‐ boundary conditions, combined with unloading due to ice melting. However, in‐situ observations are rare. In this study, we present new monitoring data from three highly instrumented boreholes, and numerical simulations to investigate rock slope temperature evolution and micrometer‐scale deformation during deglaciation. Our results show that the subsurface temperatures are adjusting to a new, warmer surface temperature following ice retreat. Heat conduction is identified as the dominant heat transfer process at sites with intact rock. Observed non‐conductive processes are related to groundwater exchange with cold subglacial water, snowmelt infiltration, or creek water infiltration. Our strain data shows that annual surface temperature cycles cause thermoelastic deformation that dominate the strain signals in the shallow thermally active layer at our stable rock slope locations. At deeper sensors, reversible strain signals correlating with pore pressure fluctuations dominate. Irreversible deformation, which we relate with progressive rock mass damage, occurs as short‐term (hours to weeks) strain events and as slower, continuous strain trends. The majority of the short‐term irreversible strain events coincides with precipitation events or pore pressure changes. Longer‐term trends in the strain time series and a minority of short‐term strain events cannot directly be related to any of the investigated drivers. We propose that the observed increased damage accumulation close to the glacier margin can significantly contribute to the long‐term formation of paraglacial rock slope instabilities during multiple glacial cycles.
Convection‐Permitting Simulations With the E3SM Global Atmosphere Model
Authors: Caldwell P. M. , Terai C. R. , Hillman B. , Keen N. D. , Bogenschutz P. , Lin W. , Beydoun H. , Taylor M. , Bertagna L. , Bradley A. M. , Clevenger T. C. , Donahue A. S. , Eldred C. , Foucar J. , Golaz J.‐C. , Guba O. , Jacob R. , Johnson J. , Krishna J. , Liu W. , Pressel K. , Salinger A. G. , Singh B. , Steyer A. , Ullrich P. , Wu D. , Yuan X. , Shpund J. , Ma H.‐Y. , Zender C. S. 
Published: October 2021

AbstractThis paper describes the first implementation of the Δx = 3.25 km version of the Energy Exascale Earth System Model (E3SM) global atmosphere model and its behavior in a 40‐day prescribed‐sea‐surface‐temperature simulation (January 20 through February 28, 2020). This simulation was performed as part of the DYnamics of the Atmospheric general circulation Modeled On Non‐hydrostatic Domains (DYAMOND) Phase 2 model intercomparison. Effective resolution is found to be the horizontal dynamics grid resolution despite using a coarser grid for physical parameterizations. Despite this new model being in an immature and untuned state, moving to 3.25 km grid spacing solves several long‐standing problems with the E3SM model. In particular, Amazon precipitation is much more realistic, the frequency of light and heavy precipitation is improved, agreement between the simulated and observed diurnal cycle of tropical precipitation is excellent, and the vertical structure of tropical convection and coastal stratocumulus look good. In addition, the new model is able to capture the frequency and structure of important weather events (e.g., tropical cyclones, extratropical cyclones including atmospheric rivers, and cold air outbreaks). Interestingly, this model does not get rid of the erroneous southern branch of the intertropical convergence zone nor the tendency for strongest convection to occur over the Maritime Continent rather than the West Pacific, both of which are classic climate model biases. Several other problems with the simulation are identified, underscoring the fact that this model is a work in progress.
Representations of Precipitation Diurnal Cycle in the Amazon as Simulated by Observationally Constrained Cloud‐System Resolving and Global Climate Models
Authors: Tai Sheng‐Lun , Feng Zhe , Ma Po‐Lun , Schumacher Courtney , Fast Jerome D. 
Published: October 2021

AbstractThe ability of an observationally‐constrained cloud‐system resolving model (Weather Research and Forecasting; WRF, 4‐km grid spacing) and a global climate model (Energy Exascale Earth System Model; E3SM, 1‐degree grid spacing) to represent the precipitation diurnal cycle over the Amazon basin during the 2014 wet season is assessed. The WRF model coupled with a 3‐D variational data assimilation scheme reproduces the spatial variability of the precipitation diurnal cycle over the basin and the lifecycle of westward propagating MCSs initiated by the coastal sea‐breeze front. In contrast, a single morning peak in rainfall is produced by E3SM for simulations despite the nudging of large‐scale winds toward global reanalysis, indicating precipitation in E3SM is largely controlled by local convection associated with diurnal heating. The role of propagating MCS on the environment are discussed by using a multivariate perturbation analysis. We also find that the advection of moisture perturbations from ocean to inland regions have a higher correlation with the occurrence of MCSs in the Amazon than the intensity of colder air intrusion associated with sea breezes along the coast. Moreover, the presence of large cold pools over the central Amazon basin are responsible for the maintenance of propagating deep convection.
Anti-reflux medication use in preterm infants
Authors: Binti Abdul Hamid Haslina , Szatkowski Lisa , Budge Helen , Ojha Shalini 
Published: October 2021

Abstract
Background
Current recommendations do not support the use of anti-reflux medications to treat gastro-oesophageal reflux disease (GORD) among preterm infants.

Objective
To describe the prevalence of GORD and the use of anti-reflux medications amongst very preterm infants (<32 weeks’ gestational age (GA)) in neonatal units in England and Wales.

Design
Retrospective cohort study using the National Neonatal Research Database.

Results
Among 58,108 infants [median GA (IQR) 29 (27–30) weeks], 15.8% (n = 9191) had a diagnosis of GORD and 36.9% (n = 12,446) received anti-reflux medications. Those who received anti-reflux medications were more preterm [GA, median (IQR): medications, 28 (26–30) vs. no medications, 30 (28–31); p < 0.001] and had lower birth weight [mean (SD): medications, 1124 g (354) vs. no medications, 1265 g (384); p < 0.001]. Most (57%, n = 12,224) received Gaviscon, or Histamine-2 Receptor Antagonist (H2RA) (56%, n = 11,959). Over time, prokinetic use has declined substantially, the use of H2RAs and Gaviscon has reduced although they continue to be used frequently, whilst the use of PPIs has increased.

Conclusions
Anti-reflux medications are frequently prescribed in very preterm infants, despite evidence to suggest that they are not effective and may be harmful. Clear guidelines for diagnosing GORD and the use of anti-reflux medications are required to rationalise the pharmacological management of GORD in preterm infants.

Impact

Anti-reflux medications are frequently prescribed, often without a diagnosis of gastro-oesophageal reflux disease, to very preterm infants while in the neonatal unit and at discharge.

Half of the infants born at <28 weeks’ gestational age receive anti-reflux medications in hospital and a quarter are discharged home on them.

Although the use of prokinetics declined following alerts of adverse events, histamine2-receptor antagonists and alginates such as Gaviscon continue to be used and the use of proton-pump inhibitors has increased more than 2-fold.
CircETFA upregulates CCL5 by sponging miR-612 and recruiting EIF4A3 to promote hepatocellular carcinoma
Authors: Lu Chen , Rong Dawei , Hui Bingqing , He Xuezhi , Jiang Wei , Xu Yetao , Cao Hongyong , Xu Zekuan , Tang Weiwei 
Published: October 2021

AbstractAs a kind of malignant tumors, hepatocellular carcinoma (HCC) has been studied continuously, but the mechanisms are not well understood. Circular RNAs (circRNAs) are widespread in eukaryotes and play an important role in the growth of organisms and in the occurrence of diseases. The role of circRNAs in HCC remains to be further explored. In this study, CircRNA microarray analysis was used to assess the plasma from HCC patients and healthy controls and to identify circRNAs involved in HCC tumorigenesis. CircETFA was overexpressed in HCC tissues, plasma, and cells. Clinicopathological data revealed that abnormally high circETFA expression was associated with a poor prognosis. In function, circETFA promotes the malignant phenotype of HCC cells in vivo and in vitro, inhibits cycle arrest, and decreases the proportion of apoptotic cells. In mechanism, it can upregulate C-C motif chemokine ligand 5 (CCL5) in HCC cells, thereby regulating the phosphoinositide 3-kinase (PI3K)/Akt pathway and other key downstream effectors (e.g., FoxO6). Furthermore, circETFA prolonged the half-life of CCL5 mRNA by recruiting the eukaryotic initiation factor 4A3 (EIF4A3) and acted as a sponge of hsa-miR-612 to suppress the silencing effect of hsa-miR-612 on CCL5. In conclusion, CircETFA can increase the expression of CCL5 to promote the progression of HCC by sponging hsa-mir-612 and recruiting EIF4A3, and is promising as a novel biomarker and therapeutic target.
Targeting CK2 in cancer: a valuable strategy or a waste of time?
Authors: Salvi Mauro , Borgo Christian , Pinna Lorenzo A. , Ruzzene Maria 
Published: October 2021

AbstractCK2 is a protein kinase involved in several human diseases (ranging from neurological and cardiovascular diseases to autoimmune disorders, diabetes, and infections, including COVID-19), but its best-known implications are in cancer, where it is considered a pharmacological target. Several CK2 inhibitors are available and clinical trials are underway in different cancer types. Recently, the suitability of CK2 as a broad anticancer target has been questioned by the finding that a newly developed compound, named SGC-CK2-1, which is more selective than any other known CK2 inhibitor, is poorly effective in reducing cell growth in different cancer lines, prompting the conclusion that the anticancer efficacy of CX-4945, the commonly used clinical-grade CK2 inhibitor, is to be attributed to its off-target effects. Here we perform a detailed scrutiny of published studies on CK2 targeting and a more in-depth analysis of the available data on SGC-CK2-1 vs. CX-4945 efficacy, providing a different perspective about the actual reliance of cancer cells on CK2. Collectively taken, our arguments would indicate that the pretended dispensability of CK2 in cancer is far from having been proved and warn against premature conclusions, which could discourage ongoing investigations on a potentially valuable drug target.
Wip1 regulates the immunomodulatory effects of murine mesenchymal stem cells in type 1 diabetes mellitus via targeting IFN-α/BST2
Authors: Zhou Na , Liu Weijiang , Zhang Wei , Liu Yuanlin , Li Xue , Wang Yang , Zheng Rongxiu , Zhang Yi 
Published: October 2021

AbstractMesenchymal stem cells (MSCs) show significant therapeutic effects in type 1 diabetes mellitus (T1DM) as regulating the inflammatory processes. However, little is known about the detailed process of MSCs immunosuppression in T1DM. In this study, we investigated the effects of wild-type p53-induce phosphatase 1 (Wip1) on regulating MSCs immunosuppressive capacities in T1DM mice. We found that Wip1 knockout (Wip1−/−) MSCs had lower therapeutic effects in T1DM mice, and displayed weaker immunosuppressive capability. In vivo distribution analysis results indicated thatWip1−/−MSCs could home to the damaged pancreas and increase the expression of tumor necrosis factor-α (TNF-α), interleukin-17a (IL-17a), interferon-α(IFN-α), IFN-β, and IFN-γ, while decrease the expression of IL-4 and IL-10. Moreover, we confirmedWip1−/−MSCs exhibited weaker immunosuppressive capacity, as evidenced by enhanced expression of bone marrow stromal cell antigen 2(BST2) and IFN-α. In conclusion, these results revealed Wip1 affects MSCs immunomodulation by regulating the expression of IFN-α/BST2. Our study uncovered that Wip1 is required to regulate the therapeutic effects of MSCs on T1DM treatment, indicating a novel role of Wip1 in MSCs immunoregulation properties.
Prediction of thermoelectric performance for layered IV-V-VI semiconductors by high-throughput ab initio calculations and machine learning
Authors: Gan Yu , Wang Guanjie , Zhou Jian , Sun Zhimei 
Published: October 2021

AbstractLayered IV-V-VI semiconductors have immense potential for thermoelectric (TE) applications due to their intrinsically ultralow lattice thermal conductivity. However, it is extremely difficult to assess their TE performance via experimental trial-and-error methods. Here, we present a machine-learning-based approach to accelerate the discovery of promising thermoelectric candidates in this chalcogenide family. Based on a dataset generated from high-throughput ab initio calculations, we develop two highly accurate-and-efficient neural network models to predict the maximum ZT (ZTmax) and corresponding doping type, respectively. The top candidate, n-type Pb2Sb2S5, is successfully identified, with the ZTmax over 1.0 at 650 K, owing to its ultralow thermal conductivity and decent power factor. Besides, we find that n-type Te-based compounds exhibit a combination of high Seebeck coefficient and electrical conductivity, thereby leading to better TE performance under electron doping than hole doping. Whereas p-type TE performance of Se-based semiconductors is superior to n-type, resulting from large Seebeck coefficient induced by high density-of-states near valence band edges.
White matter and nigral alterations in multiple system atrophy-parkinsonian type
Authors: Ogawa Takashi , Hatano Taku , Kamagata Koji , Andica Christina , Takeshige-Amano Haruka , Uchida Wataru , Kamiyama Daiki , Shimo Yasushi , Oyama Genko , Umemura Atsushi , Iwamuro Hirokazu , Ito Masanobu , Hori Masaaki , Aoki Shigeki , Hattori Nobutaka 
Published: October 2021

AbstractMultiple system atrophy (MSA) is classified into two main types: parkinsonian and cerebellar ataxia with oligodendrogliopathy. We examined microstructural alterations in the white matter and the substantia nigra pars compacta (SNc) of patients with MSA of parkinsonian type (MSA-P) using multishell diffusion magnetic resonance imaging (dMRI) and myelin sensitive imaging techniques. Age- and sex-matched patients with MSA-P (n = 21,n = 10 first and second cohorts, respectively), Parkinson’s disease patients (n = 19, 17), and healthy controls (n = 20, 24) were enrolled. Magnetization transfer saturation imaging (MT-sat) and dMRI were obtained using 3-T MRI. Measurements obtained from diffusion tensor imaging (DTI), free-water elimination DTI, neurite orientation dispersion and density imaging (NODDI), and MT-sat were compared between groups. Tract-based spatial statistics analysis revealed differences in diffuse white matter alterations in the free-water fractional volume, myelin volume fraction, and intracellular volume fraction between the patients with MSA-P and healthy controls, whereas free-water and MT-sat differences were limited to the middle cerebellar peduncle in comparison with those with Parkinson’s disease. Region-of-interest analysis of white matter and SNc revealed significant differences in the middle and inferior cerebellar peduncle, pontine crossing tract, corticospinal tract, and SNc between the MSA-P and healthy controls and/or Parkinson’s disease patients. Our results shed light on alterations to brain microstructure in MSA.
A curated diverse molecular database of blood-brain barrier permeability with chemical descriptors
Authors: Meng Fanwang , Xi Yang , Huang Jinfeng , Ayers Paul W. 
Published: October 2021

AbstractThe highly-selective blood-brain barrier (BBB) prevents neurotoxic substances in blood from crossing into the extracellular fluid of the central nervous system (CNS). As such, the BBB has a close relationship with CNS disease development and treatment, so predicting whether a substance crosses the BBB is a key task in lead discovery for CNS drugs. Machine learning (ML) is a promising strategy for predicting the BBB permeability, but existing studies have been limited by small datasets with limited chemical diversity. To mitigate this issue, we present a large benchmark dataset, B3DB, complied from 50 published resources and categorized based on experimental uncertainty. A subset of the molecules in B3DB has numerical log BB values (1058 compounds), while the whole dataset has categorical (BBB+ or BBB−) BBB permeability labels (7807). The dataset is freely available at https://github.com/theochem/B3DB and https://doi.org/10.6084/m9.figshare.15634230.v3 (version 3). We also provide some physicochemical properties of the molecules. By analyzing these properties, we can demonstrate some physiochemical similarities and differences between BBB+ and BBB− compounds.
Hypothalamic administration of sargahydroquinoic acid elevates peripheral thermogenic signaling and ameliorates high fat diet-induced obesity through the sympathetic nervous system
Authors: Kim Doyeon , Lee Yuna , Kim Hyeung-Rak , Park Yeo Jin , Hwang Hongik , Rhim Hyewhon , Kang Taek , Choi Chun Whan , Lee Bonggi , Kim Min Soo 
Published: October 2021

AbstractSargassum serratifolium (C. Agardh) C.Agardh, a marine brown alga, has been consumed as a food and traditional medicine in Asia. A previous study showed that the meroterpenoid-rich fraction of an ethanolic extract of S. serratifolium (MES) induced adipose tissue browning and suppressed diet-induced obesity and metabolic syndrome when orally supplemented. Sargahydroquinoic acid (SHQA) is a major component of MES. However, it is unclear whether SHQA regulates energy homeostasis through the central nervous system. To examine this, SHQA was administrated through the third ventricle in the hypothalamus in high-fat diet-fed C57BL/6 mice and investigated its effects on energy homeostasis. Chronic administration of SHQA into the brain reduced body weight without a change in food intake and improved metabolic syndrome-related phenotypes. Cold experiments and biochemical analyses indicated that SHQA elevated thermogenic signaling pathways, as evidenced by an increase in body temperature and UCP1 signaling in white and brown adipose tissues. Peripheral denervation experiments using 6-OHDA indicated that the SHQA-induced anti-obesity effect is mediated by the activation of the sympathetic nervous system, possibly by regulating genes associated with sympathetic outflow and GABA signaling pathways. In conclusion, hypothalamic injection of SHQA elevates peripheral thermogenic signaling and ameliorates diet-induced obesity.
M1-like macrophage contributes to chondrogenesis in vitro
Authors: Miyamoto Yoshiyuki , Kubota Keigo , Asawa Yukiyo , Hoshi Kazuto , Hikita Atsuhiko 
Published: October 2021

AbstractCartilage tissues have poor self-repairing abilities. Regenerative medicine can be applied to recover cartilage tissue damage in the oral and maxillofacial regions. However, hitherto it has not been possible to predict the maturity of the tissue construction after transplantation or to prepare mature cartilage tissues before transplantation that can meet clinical needs. Macrophages play an important role in cartilage tissue regeneration, although the exact mechanisms remain unknown. In this study, we established and verified an in vitro experimental system for the direct co-culture of cell pellets prepared from mouse auricular chondrocytes and macrophages polarized into four phenotypes (M1-like, M1, M2-like, and M2). We demonstrate that cartilage pellets co-cultured with M1-like promoted collagen type 2 and aggrecan production and induced the most significant increase in chondrogenesis. Furthermore, M1-like shifted to M2 on day 7 of co-culture, suggesting that the cartilage pellet supplied factors that changed the polarization of M1-like. Our findings suggest that cartilage regenerative medicine will be most effective if the maturation of cartilage tissues is induced in vitro by co-culture with M1-like before transplantation.
Deep learning-based thin-section MRI reconstruction improves tumour detection and delineation in pre- and post-treatment pituitary adenoma
Authors: Lee Da Hyun , Park Ji Eun , Nam Yeo Kyung , Lee Joonsung , Kim Seonok , Kim Young-Hoon , Kim Ho Sung 
Published: October 2021

AbstractEven a tiny functioning pituitary adenoma could cause symptoms; hence, accurate diagnosis and treatment are crucial for management. However, it is difficult to diagnose a small pituitary adenoma using conventional MR sequence. Deep learning-based reconstruction (DLR) using magnetic resonance imaging (MRI) enables high-resolution thin-section imaging with noise reduction. In the present single-institution retrospective study of 201 patients, conducted between August 2019 and October 2020, we compared the performance of 1 mm DLR MRI with that of 3 mm routine MRI, using a combined imaging protocol to detect and delineate pituitary adenoma. Four readers assessed the adenomas in a pairwise fashion, and diagnostic performance and image preferences were compared between inexperienced and experienced readers. The signal-to-noise ratio (SNR) was quantitatively assessed. New detection of adenoma, achieved using 1 mm DLR MRI, was not visualised using 3 mm routine MRI (overall: 6.5% [13/201]). There was no significant difference depending on the experience of the readers in new detections. Readers preferred 1 mm DLR MRI over 3 mm routine MRI (overall superiority 56%) to delineate normal pituitary stalk and gland, with inexperienced readers more preferred 1 mm DLR MRI than experienced readers. The SNR of 1 mm DLR MRI was 1.25-fold higher than that of the 3 mm routine MRI. In conclusion, the 1 mm DLR MRI achieved higher sensitivity in the detection of pituitary adenoma and provided better delineation of normal pituitary gland than 3 mm routine MRI.
Screw stripping and its prevention in the hexagonal socket of 3.5-mm titanium locking screws
Authors: Lee Hyo-Jin , Park Young Uk , Kim Sung Jae , Kim Hyong Nyun 
Published: October 2021

AbstractThere have been several reports about the difficulties in removing 3.5-mm titanium locking screws from plates due to the stripping or rounding of the hexagonal screw socket. We investigated whether stripping the locking screw sockets can be prevented by using different screwdrivers or interposing materials into the socket during removal. We overtightened 120 3.5-mm titanium locking screws (Depuy Synthes, Paoli, PA) equally into locking plates on sawbone tibia models, applying a uniform torque of 4.5 Nm, exceeding the recommended torque of 1.5 Nm. Twenty screws each were removed using a straight-handle 2.5-mm screwdriver, T-handle screwdriver, hex key wrench, and straight-handle screwdriver with a non-dominant hand. In addition, 20 screws were removed using foil from a suture packet inserted into the screw socket or using parts of a latex glove inserted into the screw socket. The incidence rates of screw stripping using the straight-handle screwdriver, T-handle screwdriver, hex key wrench, non-dominant hand, foil interposition, and latex glove interposition were 75%, 40%, 35%, 90%, 60%, and 70%, respectively. When a T-handle screwdriver or hex key wrench was used, the probability of screw stripping was 4.50 times (odds ratio = 4.50, 95% confidence interval = 1.17 to 17.37, p = 0.03) and 5.57 times (odds ratio = 5.57, 95% confidence interval = 1.42 to 21.56, p = 0.01) lower than that with the straight-handle screwdriver, respectively. Foil or latex glove interpositions did not prevent screw stripping. Thus, in the current experimental study, T-handle screwdriver or hex key wrench usage decreased the incidence rate of screw stripping during removal compared to straight-handle screwdriver use.