bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyclic Adenosine Monophosphate (cAMP)‐Dependent Phosphodiesterase Inhibition Promotes Bone Anabolism Through CD8+ T Cell Wnt‐10b Production in Mice
Authors: Roser‐Page Susanne , Weiss Daiana , Vikulina Tatyana , Yu Mingcan , Pacifici Roberto , Weitzmann M. Neale 
Published: May 2022

ABSTRACTCyclic adenosine monophosphate (cAMP)‐dependent phosphodiesterase (PDE) inhibitors such as pentoxifylline (PTX) suppress cAMP degradation and promote cAMP‐dependent signal transduction. PDE inhibitors increase bone formation and bone mass in preclinical models and are used clinically to treat psoriatic arthritis by targeting inflammatory mediators including activated T cells. T cell activation requires two signals: antigen‐dependent CD3‐activation, which stimulates cAMP production; and CD28 co‐stimulation, which downregulates cAMP‐signaling, through PDE activation. PDE‐inhibitors consequently suppress T cell activation by disrupting CD28 co‐stimulation. Interestingly, we have reported that when CD8+ T cells are activated in the absence of CD28 co‐stimulation, they secrete Wnt‐10b, a bone anabolic Wnt ligand that promotes bone formation. In the present study, we investigated whether the bone anabolic activity of the PDE‐inhibitor PTX, has an immunocentric basis, involving Wnt‐10b production by CD8+ T cells. When wild‐type (WT) mice were administered PTX, biochemical markers of both bone resorption and formation were significantly increased, with net bone gain in the axial skeleton, as quantified by micro‐computed tomography (μCT). By contrast, PTX increased only bone resorption in T cell knockout (KO) mice, causing net bone loss. Reconstituting T cell–deficient mice with WT, but not Wnt‐10b knockout (KO) CD8+ T cells, rescued bone formation and prevented bone loss. To study the role of cAMP signaling in Wnt‐10b expression, reverse‐transcription polymerase chain reaction (RT‐PCR) and luciferase‐reporter assays were performed using primary T cells. PDE inhibitors intensified Wnt‐10b promoter activity and messenger RNA (mRNA) accumulation in CD3 and CD28 activated CD8+ T cells. In contrast, inhibiting the cAMP pathway mediators protein kinase A (PKA) and cAMP response element‐binding protein (CREB), suppressed Wnt‐10b expression by T cells activated in the absence of CD28 co‐stimulation. In conclusion, the data demonstrate a key role for Wnt‐10b production by CD8+ T cells in the bone anabolic response to PDE‐inhibitors and reveal competing T cell–independent pro‐resorptive properties of PTX, which dominate under T cell–deficient conditions. Selective targeting of CD8+ T cells by PDE inhibitors may be a beneficial approach for promoting bone regeneration in osteoporotic conditions. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Co‐digestion of food waste and sewage sludge using the combination of a thermal alkali pre‐treatment and a two‐stage anaerobic digestion system
Authors: Lee Wonbae , Mo Kyung , Park Chul , Kim Dokyun , Park Seyong , Lee Dongjin , Kwon Junhwa , Kim Moonil , Cui Fenghao 
Published: May 2022

AbstractA thermal alkali pre‐treatment anaerobic digestion elutriated phased treatment (T‐ADEPT) was developed by combining the thermal‐alkali pre‐treatment (TAP) with the anaerobic digestion elutriated phased treatment (ADEPT) for the anaerobic co‐digestion of food waste (FW) and dewatered sewage sludge (SS). To improve the solubilization efficiency and methane yield, the optimal conditions for the TAP and ADEPT processes were identified. The soluble chemical oxygen demand (SCOD) solubilization, volatile suspended solids (VSS) reduction rate, volatile fatty acid (VFA) concentration, and methane yield all improved with our proposed process. The variations of the physical properties of the FW and SS mixtures confirm that the TAP process enhances the solubilization of organic matter. The methane yield of the T‐ADEPT process was 0.368 L CH4/g VSadded, which was approximately 1.4 and 1.2 times higher than the values for a conventional two‐stage anaerobic digestion (AD) process and an AD process with pre‐treatment, respectively. These results show that the application of TAP and ADEPT processes using granular sludge can be an effective approach for the anaerobic co‐digestion of FW and SS. The proposed technique is more tolerant of the inhibitory effects of high concentrations of toxic compounds compared with a conventional two‐stage AD system. Modifying a conventional anaerobic digester has the potential to deliver low hydraulic retention times (HRTs) and high organic loading rates (OLRs). © 2022 Society of Chemical Industry (SCI).
ORF8 protein of SARS‐CoV‐2 reduces male fertility in mice
Authors: Yu Ting , Ling Qiao , Xu Mengxin , Wang Niu , Wang Lixia , Lin Hanwen , Cao Manqi , Ma Yong , Wang Yuanyuan , Li Kuibiao , Du Liubing , Jin Yunyun , Li Ying , Guo Deyin , Peng Xiaoxue , Chen Yao‐qing , Zhao Bo , Pan Ji‐An 
Published: May 2022

AbstractAs one of the most rapidly evolving proteins of the genus Betacoronavirus, open reading frames (ORF8's) function and potential pathological consequence in vivo are still obscure. In this study, we show that the secretion of ORF8 is dependent on its N‐terminal signal peptide sequence and can be inhibited by reactive oxygen species scavenger and endoplasmic reticulum‐Golgi transportation inhibitor in cultured cells. To trace the effect of its possible in vivo secretion, we examined the plasma samples of coronavirus disease 2019 (COVID‐19) convalescent patients and found that the patients aged from 40 to 60 had higher antibody titers than those under 40. To explore ORF8's in vivo function, we administered the mice with ORF8 via tail‐vein injection to simulate the circulating ORF8 in the patient. Although no apparent difference in body weight, food intake, and vitality was detected between vehicle‐ and ORF8‐treated mice, the latter displayed morphological abnormalities of testes and epididymides, as indicated by the loss of the central ductal lumen accompanied by a decreased fertility in 5‐week‐old male mice. Furthermore, the analysis of gene expression in the testes between vehicle‐ and ORF8‐treated mice identified a decreased expression of Col1a1, the loss of which is known to be associated with mice's infertility. Although whether our observation in mice could be translated to humans remains unclear, our study provides a potential mouse model that can be used to investigate the impact of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection on the human reproductive system.
Long‐term evolution of cold air pools over the Madrid basin
Authors: Rasilla Domingo F. , Martilli Alberto , Allende Fernando , Fernández Felipe 
Published: May 2022

AbstractCold air pools (CAPs) are one of the most severe weather conditions experienced across many basins worldwide, related to episodes of extreme cold temperatures, poor air quality, and disruption of transportation networks. This study offers a basic climatology of CAPs in the southern Spanish Plateau and investigates its evolution since 1961 and their links with local, synoptic, and large‐scale climate variability. It is based on the comparison of meteorological records from two stations, one in the Sistema Central Range (Navacerrada, 1,894 m asl) and another at the plain (Madrid‐Barajas, 609 m asl). Accuracy and representativeness of both locations to depict the spatial and temporal variability of CAPs was also tested. CAPs days (defined as the simultaneous occurrence of a daily minimum temperature difference above 0.1°C between both stations) were found to occur year‐round, but the most frequent and intense occur in winter (NDJ). Some typical features of CAPs, such as local mesoscale processes (katabatic and anabatic flows) in connection with synoptic (advection of mid‐troposphere warm air masses during high‐pressure regimes) and hemispheric (a positive phase of the North Atlantic Oscillation) variability were also observed, leading to a sheltered boundary layer at the bottom of southern Spanish Plateau, decoupled from the free troposphere. By night, CAPs have maintained both their frequency and intensity, which means that the frequency of extremely cold nights on the plain has remained relatively stable (despite global warming). By day, an enhanced warming of the high‐elevation site has increased the temperature difference between the mountains and the plain during CAP days.
Changes in the frequency and temperature of air masses over east‐central Europe
Authors: Bartoszek Krzysztof , Kaszewski Bogusław M. 
Published: May 2022

AbstractThe study specifies the circulation conditions, the frequency of occurrence, long‐term changes, and thermal characteristics of air masses over east‐central Europe in the years 1951–2020. The division of air masses utilized by The Polish Institute of Meteorology and Water Management was used, where, based on the geographical location of the source areas, Arctic (A), Polar maritime fresh (mPf), Polar maritime old (transformed) (mPo), Polar maritime warm (mPw), Polar continental (cP), and Tropical (T) air masses are distinguished. It has been shown that western circulation dominates in this area (60% of days on average), during which the advection of maritime air masses occurs. The share of Arctic air mass flowing from the north (about 12% of days a year) and Tropical air mass from the southern sector (4% of days) is clearly smaller. The results of the research have shown that the frequency of the majority of the analysed air masses was subject to short‐term changes in the studied period. On the other hand, long‐term changes in this frequency concerned two air masses flowing from lower latitudes (mPw and T). In the case of mPw, in the period 1951–2020 there was a significant increase in frequency, not only on a yearly basis, but also in all seasons. In the last two decades, the frequency of Tropical air mass has also increased significantly, while the increase took place only in the summer period. Therefore, the increase in air temperature recorded in east‐central Europe since the 1990s, mainly in the warm half of the year, should to a large extent be attributed to both the greater frequency of the inflow of air masses from lower latitudes (mPw and T) and the increase in temperature in virtually all separated air masses, which in turn is a result of progressing global warming.
Analysis of requirements for developing a mobile device‐based medicines management application for people who are blind and visually impaired
Authors: Dinari Fatemeh , Bahaadinbeigy Kambiz , Moulaei Khadijeh 
Published: May 2022

AbstractBackgroundPeople with visual impairments are often faced with challenges in the process of medicines management and use. Mobile device‐based applications can be a potential solution in reducing these challenges.ObjectivesThis study aimed to analyse the requirements for developing a mobile device‐based medicines management application for people who are blind and visually impaired.MethodsA questionnaire was designed to examine the requirements for developing a medicines management application for people who were blind and visually impaired. The questionnaire was sent to 2081 people who are blind or visually impaired, and their instructors. Among them, 146 people (125 with visual impairments and 21 instructors) completed the questionnaire. SPSS 23 software was used for statistical analysis.ResultsNinety percent of people with visual impairments and 75% of instructors were willing to assist in application design. Out of 44 data elements, 35 were considered important for designing and creating mobile device‐based medicines management applications. ‘Providing education information about drugs in the form of audio files’ (4.71 ± 0.56), ‘Ability to update software’ (4.71 ± 0.56) and ‘Ability to search for physician’s addresses’ (4.71 ± 0.46) were rated highest, in terms of required ‘Application capabilities’, by the study cohort based on average Likert scale scores (1 = very low, 2 = low, 3 = moderate, 4 = high, 5 = very high).ConclusionThis study provides a set of data elements that people who are blind and visually impaired, and their instructors, have identified as being important to the development and design of mobile device‐based medicines management applications. Developers can use the identified data elements to help in the design and implementation of their medicines management applications or electronic systems. Applications and electronic systems that incorporate features for people who are blind and visually impaired, have the potential to improve quality of life by enabling independent medicines management and medicines adherence, whilst potentially decreasing medication errors, rate of diseases, frequency of hospitalisations and medicines related deaths.
A Deep Learning Model for Classification of Parotid Neoplasms Based on Multimodal Magnetic Resonance Image Sequences
Authors: Liu Xu , Pan Yucheng , Zhang Xin , Sha Yongfang , Wang Shihui , Li Hongzhe , Liu Jianping 
Published: May 2022

ObjectiveTo design a deep learning model based on multimodal magnetic resonance image (MRI) sequences for automatic parotid neoplasm classification, and to improve the diagnostic decision‐making in clinical settings.MethodsFirst, multimodal MRI sequences were collected from 266 patients with parotid neoplasms, and an artificial intelligence (AI)‐based deep learning model was designed from scratch, combining the image classification network of Resnet and the Transformer network of Natural language processing. Second, the effectiveness of the deep learning model was improved through the multi‐modality fusion of MRI sequences, and the fusion strategy of various MRI sequences was optimized. In addition, we compared the effectiveness of the model in the parotid neoplasm classification with experienced radiologists.ResultsThe deep learning model delivered reliable outcomes in differentiating benign and malignant parotid neoplasms. The model, which was trained by the fusion of T2‐weighted, postcontrast T1‐weighted, and diffusion‐weighted imaging (b = 1000 s/mm2), produced the best result, with an accuracy score of 0.85, an area under the receiver operator characteristic (ROC) curve of 0.96, a sensitivity score of 0.90, and a specificity score of 0.84. In addition, the multi‐modal paradigm exhibited reliable outcomes in diagnosing the pleomorphic adenoma and the Warthin tumor, but not in the identification of the basal cell adenoma.ConclusionAn accurate and efficient AI based classification model was produced to classify parotid neoplasms, resulting from the fusion of multimodal MRI sequences. The effectiveness certainly outperformed the model with single MRI images or single MRI sequences as input, and potentially, experienced radiologists.Level of Evidence3 Laryngoscope, 133:327–335, 2023
Bisurfactant‐functionalized TiO2 nanoparticles as additives of the lubricating oil
Authors: Ma Hongxia , Wu Wei , Wang Zeyun 
Published: May 2022

AbstractIn this work, TiO2 nanoparticles modified with octadecylamine and dodecyl mercaptan (DDM/ODA@PDA@TiO2 NPs) are uesd to improve the tribological properties of the white oil. The DDM/ODA@PDA@TiO2 NPs which are simply prepared by mussel inspired chemistry and the Michael addition reaction can be facilely dispersed in the white base oil. Tribological measurements showed that the dispersion of the white oil containing 3 wt% DDM/ODA@PDA@TiO2 NPs displays significant reductions in the friction coefficient and wear scar diameter at room temperature and 75°C. Further XPS investigation shows that the favourable tribological properties of DDM/ODA@PDA@TiO2 NPs are ascribed to the synergistic effect of tribofilm (Fe2O3, Fe3O4, FeS2, FeS and FeSO4) and TiO2 nanofluids.
CAQ Corner: Surgical evaluation for liver transplantation
Authors: Misra Asish C. , Emamaullee Juliet 
Published: May 2022

Abstract
The evaluation of a liver transplantation candidate is a complex and detailed process that in many cases must be done in an expedited manner because of the critically ill status of some patients with end‐stage liver disease. It involves great effort from and the collaboration of multiple disciplines, and during the evaluation several studies and interventions are performed to assess and potentially prepare a patient for liver transplant. Here we review the liver transplantation evaluation from a surgical perspective.
Characterization and microsatellite marker development for a common bark and ambrosia beetle associate, Geosmithia obscura
Authors: Pietsch Grace M. , Gazis Romina , Klingeman William E. , Huff Matthew L. , Staton Margaret E. , Kolarik Miroslav , Hadziabdic Denita 
Published: May 2022

AbstractSymbioses between Geosmithia fungi and wood‐boring and bark beetles seldom result in disease induction within the plant host. Yet, exceptions exist such as Geosmithia morbida, the causal agent of Thousand Cankers Disease (TCD) of walnuts and wingnuts, and Geosmithia sp. 41, the causal agent of Foamy Bark Canker disease of oaks. Isolates of G. obscura were recovered from black walnut trees in eastern Tennessee and at least one isolate induced cankers following artificial inoculation. Due to the putative pathogenicity and lack of recovery of G. obscura from natural lesions, a molecular diagnostic screening tool was developed using microsatellite markers mined from the G. obscura genome. A total of 3256 candidate microsatellite markers were identified (2236, 789, 137 di‐, tri‐, and tetranucleotide motifs, respectively), with 2011, 703, 101 di‐, tri‐, and tetranucleotide motifs, respectively, containing markers with primers. From these, 75 microsatellite markers were randomly selected, screened, and optimized, resulting in 28 polymorphic markers that yielded single, consistently recovered bands, which were used in downstream analyses. Five of these microsatellite markers were found to be specific to G. obscura and did not cross‐amplify into other, closely related species. Although the remaining tested markers could be useful, they cross‐amplified within different Geosmithia species, making them not reliable for G. obscura detection. Five novel microsatellite markers (GOBS9, GOBS10, GOBS41, GOBS43, and GOBS50) were developed based on the G. obscura genome. These species‐specific microsatellite markers are available as a tool for use in molecular diagnostics and can assist future surveillance studies.
Seasonal phytoplankton and geochemical shifts in the subsurface chlorophyll maximum layer of a dimictic ferruginous lake
Authors: Swanner Elizabeth D. , Wüstner Marina , Leung Tania , Pust Jürgen , Fatka Micah , Lambrecht Nick , Chmiel Hannah E. , Strauss Harald 
Published: May 2022

AbstractSubsurface chlorophyll maxima layers (SCML) are ubiquitous features of stratified aquatic systems. Availability of the micronutrient iron is known to influence marine SCML, but iron has not been explored in detail as a factor in the development of freshwater SCML. This study investigates the relationship between dissolved iron and the SCML within the dimictic, ferruginous lake Grosses Heiliges Meer in northern Germany. The occurrence of the SCML under nonferruginous conditions in the spring and ferruginous conditions in the fall are context to explore temporal changes in the phytoplankton community and indicators of primary productivity. Results indicate that despite more abundant chlorophyll in the spring, the SCML sits below a likely primary productivity maximum within the epilimnion, inferred based on colocated dissolved oxygen, δ13CDIC, and pH maxima. The peak amount of chlorophyll in the SCML is lower in the fall than in the spring, but in the fall the SCML is colocated with elevated dissolved iron concentrations and a local δ13CDICmaximum. Cyanobacteria and Chlorophyta have elevated abundances within the SCML in the fall. Further investigation of the relationship of iron to primary productivity within ferruginous SCML may help to understand the environmental controls on primary productivity in past ferruginous oceans.
Crystallographic landscape of SHP2 provides molecular insights for SHP2 targeted drug discovery
Authors: Song Yihui , Yang Xinyu , Wang Shu , Zhao Min , Yu Bin 
Published: May 2022

AbstractThe protein tyrosine phosphatase SHP2 encoded by PTPN11 is a promising therapeutic target for cancer therapy. The dynamic change of SHP2 between closed and open conformations under either physiological or pathological conditions provides opportunities to design SHP2 inhibitors for treating SHP2‐related diseases. To date, several SHP2 allosteric inhibitors have advanced into clinical trials as mono‐ or combined therapy of cancers. In this review, we provide an overview on the structural landscape of SHP2 under physiological and pathological conditions and also comprehensively analyze the binding models of SHP2/inhibitor complexes. Structural features of SHP2 under pathological conditions and co‐crystal structures of SHP2/inhibitor complexes will definitely facilitate structure‐guided design of SHP2 inhibitors. Finally, proteolysis targeting chimeric (PROTAC) based SHP2 degraders have shown therapeutic promise for cancer therapy and are also briefly discussed. We hope this review could provide crystallographic landscape for SHP2 targeted drug discovery.
Small‐molecule inhibitors of cyclophilin D as potential therapeutics in mitochondria‐related diseases
Authors: Haleckova Annamaria , Benek Ondrej , Zemanová Lucie , Dolezal Rafael , Musilek Kamil 
Published: May 2022

AbstractCyclophilin D (CypD) is a key regulator of mitochondrial permeability transition pore (mPTP) opening. This pathophysiological phenomenon is associated with the development of several human diseases, including ischemia‐reperfusion injury and neurodegeneration. Blocking mPTP opening through CypD inhibition could be a novel and promising therapeutic approach for these conditions. While numerous CypD inhibitors have been discovered to date, none have been introduced into clinical practice, mostly owing to their high toxicity, unfavorable pharmacokinetics, and low selectivity for CypD over other cyclophilins. This review summarizes current knowledge of CypD inhibitors, with a particular focus on small‐molecule compounds with regard to their in vitro activity, their selectivity for CypD, and their binding mode within the enzyme's active site. Finally, approaches for improving the molecular design of CypD inhibitors are discussed.
On partially observed optimal singular control of McKean–Vlasov stochastic systems: Maximum principle approach
Authors: Abada Nour El Houda , Hafayed Mokhtar , Meherrem Shahlar 
Published: May 2022

In this paper, we study partially observed optimal stochastic singular control problems of general Mckean–Vlasov type with correlated noises between the system and the observation. The control variable has two components, the first being absolutely continuous and the second is a bounded variation, nondecreasing continuous on the right with left limits. The dynamic system is governed by Itô‐type controlled stochastic differential equation. The coefficients of the dynamic depend on the state process and of its probability law and the continuous control variable. In terms of a classical convex variational techniques, we establish a set of necessary conditions of optimal singular control in the form of maximum principle. Our main result is proved by applying Girsanov's theorem and the derivatives with respect to probability law in Lions' sense. To illustrate our theoretical result, we study partially observed linear‐quadratic singular control problem of McKean–Vlasov type.