bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cholesterol absorption blocker ezetimibe prevents muscle wasting in severe dysferlin‐deficient and mdx mice
Authors: White Zoe , Theret Marine , Milad Nadia , Tung Lin Wei , Chen William Wei‐Han , Sirois Martin G. , Rossi Fabio , Bernatchez Pascal 
Published: December 2021

AbstractBackgroundMuscular dystrophy (MD) causes muscle wasting and is often lethal in patients due to a lack of proven therapies. In contrast, mouse models of MD are notoriously mild. We have previously shown severe human‐like muscle pathology in mdx [Duchenne MD (DMD)] and dysferlin‐deficient limb‐girdle MD type 2B (LGMD2B) mice by inactivating the gene encoding for apolipoprotein E (ApoE), a lipid transporter synthesized by the liver, brain and adipocytes to regulate lipid and fat metabolism. Having recently established that human DMD is a novel type of primary genetic dyslipidaemia with elevated cholesterol, we sought to determine whether cholesterol could exacerbate the muscle wasting process observed in severe rodent MD.MethodsSevere mdx and dysferlin knock‐out mice lacking ApoE were treated with ezetimibe (15 mg/kg/day), a clinically approved drug exhibiting few pleiotropic effects. In separate studies, dietary cholesterol was raised (from 0.2% to 2% cholesterol) in combination with experimental micro‐injury and direct cholesterol injection assays. Muscles were assessed histologically for changes in collagen and adipocyte infiltration and both transcriptomic and cellular changes by RNA‐seq and fluorescence‐activated cell sorting analysis.ResultsTreatment of severe DMD and LGMD2B mice with ezetimibe completely prevented clinical signs of ambulatory dysfunction (0% incidence vs. 33% for vehicle treatment; P < 0.05). Histological analyses revealed that ezetimibe‐reduced fibro‐fatty infiltration up to 84% and 63% in severely affected triceps (P ≤ 0.0001) and gastrocnemius (P ≤ 0.003) muscles, resulting in a respective 1.9‐fold and 2.2‐fold retention of healthy myofibre area (P ≤ 0.0001). Additionally, raising dietary cholesterol and thus concentrations of plasma low‐density lipoprotein‐associated cholesterol (by 250%; P < 0.0001) reduced overall survivability (by 100%; P < 0.001) and worsened muscle damage in the LGMD2B triceps by 767% (P < 0.03). Micro‐pin‐induced mechanical injury in LGMD2B mice fed a high cholesterol diet exacerbated muscle damage by 425% (P < 0.03) and increased macrophage recruitment (by 98%; P = 0.03) compared with those injured on a chow diet. Parallel RNA‐seq analyses revealed that injury in cholesterol‐fed mice also modulated the expression of 3671 transcripts (1953 up‐regulated), with fibrogenic, inflammatory and programmed cell death‐associated pathways among the most enriched. Mice lacking dysferlin also displayed heightened muscle necrosis (by 123%; P < 0.0001) following a direct intramuscular injection of cholesterol compared with control mice.ConclusionsCholesterol exacerbates rodent MD. Specific inhibition of cholesterol absorption with ezetimibe may safely attenuate human MD severity and delay death.
Influence of preceding North Atlantic Oscillation on the spring precipitation in the middle and lower reaches of the Yangtze River valley
Authors: Han Jinping , Zhang Renhe 
Published: December 2021

AbstractThe relationship between the spring precipitation in the middle and lower reaches of the Yangtze River valley and the North Atlantic Oscillation in the preceding winter is investigated based on data diagnosis. Through affecting the dynamics and thermodynamics in near‐surface atmosphere over Eurasia, the North Atlantic Oscillation in January can exert significant influence on the Eurasian snow cover to form a dipole pattern of snow anomalies. The dipole pattern of snow anomalies stimulates the Rossby wave train in the middle and high latitudes of the Northern Hemisphere in the following spring. Two activity centres associated with the wave train, one in the middle latitudes of Northwest Pacific with an anomalous anticyclone circulation and another in Mongolia with an anomalous cyclone circulation, bring the water vapour from the south and converge over the middle and lower reaches of the Yangtze River, resulting in the excessive precipitation over there. The results indicate that the North Atlantic Oscillation in January can act as a precursor signal for predicting the spring rainfall anomalies in the middle and lower reaches of the Yangtze River.
Variations in the probability distribution function of air temperature anomalies in winter and summer from 1961 to 2016 over China
Authors: Wu Guocan , Tian Yuan , Gong Fang , Du Jizeng , Shi Chunming 
Published: December 2021

AbstractThe rising of near‐surface air temperature is the most obvious manifestation of global warming. The analysis of the probability distribution function (PDF) of temperature can deep our understanding of the current characteristics of climate and extreme temperature changes. In this study, the daily maximum, minimum and mean temperature observations from meteorological stations are analysed to construct the temperature anomaly PDF during 1961–2016 over China. The skewness and kurtosis of the PDF are compared between the 1961–1990 and 1991–2016 periods. The non‐Gaussian tails of the PDF are also identified to qualify the deviation of the temperature probability density curve. The results show that near‐surface air temperature in China increased during the recent decades. The daily minimum temperature increased more than the daily maximum temperature did, while the temperature increase in winter was larger than that in summer. The largest increase detected was 1.29°C for the daily minimum temperature in winter, contrasting with the smallest increase of 0.51°C recorded for the daily minimum temperature in summer between the two study periods. The temperature anomaly PDF generally presented a positive skewness in winter and a slightly negative skewness in summer. Obvious non‐Gaussian tails in the temperature anomaly PDF were present in the majority of the study sites. Most areas showed a short cold tail in winter (except for southwestern China), and long cold tails were mainly observed in summer. These results can improve our understanding of the variation of extreme temperatures, and of the responses to global warming.
Micro‐Raman spectroscopy and complementary techniques for the study of iron weapons from Motya and Lilybaeum (Sicily, Italy): Corrosion patterns in lagoon‐like and calcarenitic hypogea environments
Authors: Bernabale Martina , Nigro Lorenzo , Vaccaro Carmela , Nicoli Maria , Montanari Daria , Bigini Pierpaolo , De Vito Caterina 
Published: December 2021

AbstractMicro‐Raman spectroscopy (μ‐RS) has been used to characterize mineralogical phases of corroded iron materials, buried in lagoon‐like and calcarenitic hypogea environments. A set of samples from the Phoenician site of Motya (8th–6th centuries BC, Sicily) and from the Punic Necropolis of Lilybaeum (4th century BC, Sicily) were analyzed combining μ‐RS with scanning electron microscopy‐energy‐dispersive X‐ray spectroscopy (SEM‐EDS) and high‐resolution field emission scanning electron microscopy (HR‐FESEM). Micro‐Raman results revealed the presence of magnetite, goethite, lepidocrocite, and hematite as the main corrosion products and soil minerals as quartz, calcite, barite, actinolite, microcline, zircon, and Ti‐oxides. SEM and HR‐FESEM allowed exploring micro‐ and sub‐micrometer structures of iron oxy‐hydroxides though sections from rim to core. The different corrosion models suggest polymorphic inter‐conversions among iron oxy‐hydroxides and dissolution‐re‐precipitation reactions. In addition, the occurrence of magnetite and metal core that survived in armors buried in the hypogea site of Lilybaeum indicates more stable environmental conditions than those of Motya.
Exploring the binding mechanism of ferulic acid and ovalbumin: insights from spectroscopy, molecular docking and dynamics simulation
Authors: Chen Lei , Zhu Miao , Hu Xing , Pan Junhui , Zhang Guowen 
Published: December 2021

AbstractBACKGROUNDFerulic acid (FA), a phenolic acid widely occurring in nature, has attracted extensive attention because of its biological activity. Ovalbumin (OVA) is a commonly used carrier protein. The mechanism of FA binding with OVA was investigated by utilizing a variety of spectral analyses, accompanied by computer simulation.RESULTSIt was discovered that the fluorescence quenching mechanism of OVA by FA was a static mode as a result of the formation of an FA−OVA complex, which was verified by the concentration distributions and pure spectrum of the constituents decomposed from the high overlap spectrum signals using multivariate curve resolution–alternate least squares algorithm. Hydrogen bonds and Van der Waals forces drove the formation of FA–OVA complex with a binding constant of 1.69 × 104 L mol−1. The presence of FA induced the loose structure of OVA with an attenuation of α‐helix content and improved the thermal stability of OVA. Computer docking indicated that FA interacted with the amino acid residues Arg84, Asn88, Leu101 and Ser103 of OVA through hydrogen bonds. Molecular dynamics simulation proved that the combination of FA with OVA boosted the conformational stability of OVA and hydrogen bonds brought a crucial part in stabilizing the structure of the complex.CONCLUSIONSThe study may supply the theoretical basis for the design of FA transport system using OVA as carrier protein to improve the instability and low bioavailability of FA. © 2021 Society of Chemical Industry.
The role of necroptosis in disease and treatment
Authors: Liu Xiaoxiao , Xie Xin , Ren Yuanyuan , Shao Zhiying , Zhang Nie , Li Liantao , Ding Xin , Zhang Longzhen 
Published: December 2021

AbstractNecroptosis, a distinctive type of programmed cell death different from apoptosis or necrosis, triggered by a series of death receptors such as tumor necrosis factor receptor 1 (TNFR1), TNFR2, and Fas. In case that apoptosis process is blocked, necroptosis pathway is initiated with the activation of three key downstream mediators which are receptor‐interacting serine/threonine protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain‐like protein (MLKL). The whole process eventually leads to destruction of the cell membrane integrity, swelling of organelles, and severe inflammation. Over the past decade, necroptosis has been found widely involved in life process of human beings and animals. In this review, we attempt to explore the therapeutic prospects of necroptosis regulators by describing its molecular mechanism and the role it played in pathological condition and tissue homeostasis, and to summarize the research and clinical applications of corresponding regulators including small molecule inhibitors, chemicals, Chinese herbal extracts, and biological agents in the treatment of various diseases.
A Novel SPAST Mutation Results in Spastin Accumulation and Defects in Microtubule Dynamics
Authors: Chen Rui , Du Shiyue , Yao Yanyi , Zhang Lu , Luo Junyu , Shen Yinhua , Xu Zhenping , Zeng Xiaomei , Zhang Luoying , Liu Mugen , Yin Chuang , Tang Beisha , Tan Jun , Xu Xuan , Liu Jing Yu 
Published: December 2021

ABSTRACTBackgroundHaploinsufficiency is widely accepted as the pathogenic mechanism of spastic paraplegia type 4 (SPG4). However, there are some cases that cannot be explained by reduced function of the spastin protein encoded by SPAST.ObjectivesTo identify the causative gene of autosomal dominant hereditary spastic paraplegia in three large Chinese families and explore the pathological mechanism of a spastin variant.MethodsThree large Chinese hereditary spastic paraplegia families with a total of 247 individuals (67 patients) were investigated, of whom 59 members were recruited to the study. Genetic testing was performed to identify the causative gene. Western blotting and immunofluorescence were used to analyze the effects of the mutant proteins in vitro.ResultsIn the three hereditary spastic paraplegia families, of whom three index cases were misdiagnosed as other types of neurological diseases, a novel c.985dupA (p.Met329Asnfs*3) variant in SPAST was identified and was shown to cosegregate with the phenotype in the three families. The c.985dupA mutation produced two truncated mutants (mutant M1 and M87 isoforms) that accumulated to a higher level than their wild‐type counterparts. Furthermore, the mutant M1 isoform heavily decorated the microtubules and rendered them resistant to depolymerization. In contrast, the mutant M87 isoform was diffusely localized in both the nucleus and the cytoplasm, could not decorate microtubules, and was not able to promote microtubule disassembly.ConclusionsSPAST mutations leading to premature stop codons do not always act through haploinsufficiency. The truncated spastin may damage the corticospinal tracts through an isoform‐specific toxic effect.
Numerical simulation of cold and hot water injection into naturally fractured porous media using the extended–FEM and an equivalent continuum model
Authors: Mortazavi S. Mohammad S. , Pirmoradi Pouriya , Khoei Amir R. 
Published: December 2021

AbstractIn this paper, a computational technique is presented for the isothermal and non‐isothermal water injection into naturally fractured oil reservoirs. A remarkable number of naturally fractured reservoirs contain relatively heavy oils that could not be extracted economically; hence, the thermal recovery methods are extensively used for such reservoirs. In this study, the effectiveness of hot water injection over cold (isothermal) water injection in oil production is quantified. The influence of long and short fractures and their alignments on oil recovery are discussed. To this end, a 2D model for two‐phase fluid flow and heat transfer is presented. The medium is assumed to be partially saturated with water as the wetting phase and oil as the non‐wetting phase. The governing equations consist of the energy balance equation together with the continuity equations of both fluid phases. To take the long (macro) fractures into account, the extended finite element method is employed by considering permeable fracture faces; accordingly, the mass and heat transfer between the fracture and the matrix are captured accurately. In addition, the network of short (micro) fractures is incorporated by an equivalent continuum model. Several numerical examples are presented to demonstrate the influence of injection temperature, initial reservoir temperature, and the long and short fractures on oil production. Furthermore, the simultaneous effect of the macro‐ and micro‐fractures along with the injection temperature are examined. The results show that the proposed computational model is a promising tool that can be used in the cold or hot water injection, and can be employed in the economic feasibility studies of recovery methods in the future.
amulog: A general log analysis framework for comparison and combination of diverse template generation methods*
Authors: Kobayashi Satoru , Yamashiro Yuya , Otomo Kazuki , Fukuda Kensuke 
Published: December 2021

SummaryOne of the ways to analyze unstructured log messages from large‐scale IT systems is to classify log messages with log templates generated by template generation methods. However, there is currently no common knowledge pertained to the comparison and practical use of log template generation methods because they are implemented on the basis of diverse environments. To this end, we design and implement amulog, a general log analysis framework for comparing and combining diverse log template generation methods. Amulog consists of three key functions: (1) parsing log messages into headers and segmented messages, (2) classifying the log messages using a scalable template‐matching method, and (3) storing the structured data in a database. This framework helps us easily utilize time‐series data corresponding to the log templates for further analysis. We evaluate amulog with a log dataset collected from a nation‐wide academic network and demonstrate that it classifies the log data in a reasonable amount of time even with over 100,000 log template candidates. The template‐matching method in amulog also reduces 75% processing time for template generation and keeps the accuracy when combined with an existing structure‐based template generation method. In order to show the effectiveness of amulog in comparing log template generation methods, we demonstrate that the appropriate template generation methods and accuracy metrics largely depend on the purpose of further analysis by comparing the accuracy of six existing log template generation methods with 10 different accuracy metrics on amulog.
Structural, morphological, optical, and dielectric properties of PVA‐PVP filled with zinc oxide aluminum‐graphene oxide composite for promising applications
Authors: Mohamed Fathia , Sharmoukh Walid , Youssef Ahmed M. , Hameed Talaat A. 
Published: December 2021

AbstractPolymer nanocomposites of poly (vinyl alcohol) (PVA), poly (vinyl pyrrolidone) (PVP) filled with various concentration of nanocomposite (Zn0.97Al0.03O: 1 wt% GO)x; x = 1, 3, 5, and 7 wt% were prepared by solution mixing and then cast into films. X‐ray combined with energy dispersive spectroscopy (EDS) data elucidated the successful preparation of pure PVA/PVP and filled films. The identifiable diffraction lines are ascribable to the presence of filler (Zn0.97Al0.03O: 1 wt% GO) that further established by the data of EDS as well as selected area electron diffraction pattern (SAED) achieved by high‐resolution transmission electron microscopy (HRTEM) measurement. The optical band gap (Eg) of composite shows a significant decrement from 5.2 to 4.7 eV as the nanocomposite fillers were varied from 0 to 7 wt%. In addition, the refractive index (n), optical dielectric loss (ε2), and optical conductivity (σopt) were investigated. The PVA/PVP filled with merely 1 wt% of the particle has an extremely high dielectric permittivity and conductivity.
Influence of the cure state on mechanical properties of an epoxy‐based adhesive: Experimental characterization and numerical simulation
Authors: Teixeira Paulo , Akhavan‐Safar Alireza , Carbas Ricardo J. C. , da Silva Lucas F. M. 
Published: December 2021

AbstractHeat curing epoxy‐based adhesives are extensively used in primary bonded structures. The manufacturing process of joints with heat curing adhesives is commonly made with isothermal processes where a large curing time is set to guarantee the complete curing of the adhesive. The aim of the current study is to investigate the influence of the curing state on the tensile mechanical properties of a structural one‐component epoxy based adhesive. To achieve this, tensile tests on bulk adhesive dog‐bone coupons with incomplete curing were performed. The process cycle was adjusted to achieve the desired curing degree for testing. The curing process was simulated by using the Kamal kinetics model calibrated with differential scanning calorimetry (DSC) tests. The results show that the curing process is very sensitive to the curing temperature, requiring a low curing temperature to control process duration. A good correlation between the estimated curing degree and the final obtained curing measured with the Fourier‐transform infrared spectroscopy FTIR was found. Regarding the mechanical properties, the elastic modulus and the tensile strength are reduced at lower curing degrees making the material softer and more ductile. The loss in the mechanical properties shows to be consistent with the measurements performed with dynamical mechanical analyses (DMA) by measuring the evolution of the elastic modulus with the curing degree. In this way, the numerical simulation of the curing process seems to be a valuable tool to predict the final performance of adhesive, and design the curing cycle.
5‐Alpha reductase inhibitors induce a prostate luminal to club cell transition in human benign prostatic hyperplasia
Authors: Joseph Diya B , Henry Gervaise H , Malewska Alicia , Reese Jeffrey C , Mauck Ryan J , Gahan Jeffrey C , Hutchinson Ryan C , Mohler James L , Roehrborn Claus G , Strand Douglas W 
Published: December 2021

AbstractBenign prostatic hyperplasia (BPH) is a progressive expansion of peri‐urethral prostate tissue common in aging men. Patients with enlarged prostates are treated with 5‐alpha reductase inhibitors (5ARIs) to shrink prostate volume by blocking the conversion of testosterone to dihydrotestosterone (DHT). A reduction in DHT levels can elicit atrophy and apoptosis of prostate secretory luminal cells, which results in a favorable clinical response characterized by improved lower urinary tract symptoms. However, the histologic response to 5ARI treatment is often heterogeneous across prostate acini and lower urinary tract symptoms can persist to require surgical intervention. We used two spatial profiling approaches to characterize gene expression changes across histologically normal and atrophied regions in prostates from 5ARI‐treated men. Objective transcriptomic profiling using the Visium spatial gene expression platform showed that 5ARI‐induced atrophy of prostate luminal cells correlated with reduced androgen receptor signaling and increased expression of urethral club cell genes including LTF, PIGR, OLFM4, SCGB1A1, and SCGB3A1. Prostate luminal cells within atrophied acini adapted to decreased DHT conditions by increasing NF‐κB signaling and anti‐apoptotic BCL2 expression, which may explain their survival. Using GeoMx digital spatial profiling with a probe set to assess ~18 000 RNA targets, we confirmed that atrophied acini expressing SCGB3A1 displayed higher levels of club cell markers compared with histologically normal acini with NKX3‐1 expression. In addition, club‐like cells within regions of 5ARI‐induced atrophy closely resembled true club cells from the prostatic urethra. A comparison of histologically normal regions from 5ARI‐treated men and histologically normal regions from untreated men revealed few transcriptional differences. Taken together, our results describe a heterogeneous response to 5ARI treatment where cells in atrophied acini undergo an adaptation from a prostate secretory luminal to a club cell‐like state in response to 5ARI treatment. © 2021 The Pathological Society of Great Britain and Ireland.
Psychosocial impact of proactive rapid genetic counseling following breast cancer diagnosis
Authors: Kritzik Rachel , Usoro Edidiong , Peshkin Beth N. , Isaacs Claudine , Valdimarsdottir Heiddis B. , Willey Shawna , O’Neill Suzanne , DeMarco Tiffani , Nusbaum Rachel , Jandorf Lina , Kelleher Sarah , Schwartz Marc D. 
Published: December 2021

AbstractObjectiveAs germline genetic referral becomes increasingly routine as part of the care of newly diagnosed breast cancer patients, it is important to understand the psychosocial impact of genetic counseling at the time of diagnosis. We examined the psychosocial and quality of life (QOL) impact of providing proactive rapid genetic counseling and testing (RGCT) in the immediate aftermath of a breast cancer diagnosis.MethodsWe randomized 330 patients in a 2:1 ratio to proactive rapid genetic counseling (RGCT; N = 222) versus usual care (UC; N = 108). Participants completed a baseline telephone survey before randomization and definitive surgery and a follow‐up survey at 1‐month post‐randomization. We evaluated the impact of RGCT versus UC on breast cancer genetic knowledge, distress, QOL, and decisional conflict. Given that 43% of UC participants and 86% of RGCT participants completed genetic counseling prior to the 1‐month assessment, we also evaluated the impact of genetic counseling participation over and above group assignment.ResultsThe RGCT intervention led to increased breast cancer genetic knowledge relative to UC but did not differentially impact other study outcomes. Across groups patients who participated in genetic counseling had significantly increased knowledge and improved QOL compared to those who did not participate in genetic counseling.ConclusionsWhile prior research has documented the impact of genetic counseling and testing on surgical decisions, these results confirm that participation in genetic counseling at the time of diagnosis can yield improvements in knowledge and QOL in the short‐term.