bluuebunny/crossref_metadata_2025 huggingface dataset:
Auranofin mitigates systemic iron overload and induces ferroptosis via distinct mechanisms
Authors: Yang Lei , Wang Hao , Yang Xiang , Wu Qian , An Peng , Jin Xi , Liu Weiwei , Huang Xin , Li Yuzhu , Yan Shiyu , Shen Shuying , Liang Tingbo , Min Junxia , Wang Fudi
Published: July 2020

Iron homeostasis is essential for health; moreover, hepcidin-deficiency results in iron overload in both hereditary hemochromatosis and iron-loading anemia. Here, we identified iron modulators by functionally screening hepcidin agonists using a library of 640 FDA-approved drugs in human hepatic Huh7 cells. We validated the results in C57BL/6J mice and a mouse model of hemochromatosis (Hfe−/− mice). Our screen revealed that the anti-rheumatoid arthritis drug auranofin (AUR) potently upregulates hepcidin expression. Interestingly, we found that canonical signaling pathways that regulate iron, including the Bmp/Smad and IL-6/Jak2/Stat3 pathways, play indispensable roles in mediating AUR’s effects. In addition, AUR induces IL-6 via the NF-κB pathway. In C57BL/6J mice, acute treatment with 5 mg/kg AUR activated hepatic IL-6/hepcidin signaling and decreased serum iron and transferrin saturation. Whereas chronically treating male Hfe−/− mice with 5 mg/kg AUR activated hepatic IL-6/hepcidin signaling, decreasing systemic iron overload, but less effective in females. Further analyses revealed that estrogen reduced the ability of AUR to induce IL-6/hepcidin signaling in Huh7 cells, providing a mechanistic explanation for ineffectiveness of AUR in female Hfe−/− mice. Notably, high-dose AUR (25 mg/kg) induces ferroptosis and causes lipid peroxidation through inhibition of thioredoxin reductase (TXNRD) activity. We demonstrate the ferroptosis inhibitor ferrostatin significantly protects liver toxicity induced by high-dose AUR without comprising its beneficial effect on iron metabolism. In conclusion, our findings provide compelling evidence that TXNRD is a key regulator of ferroptosis, and AUR is a novel activator of hepcidin and ferroptosis via distinct mechanisms, suggesting a promising approach for treating hemochromatosis and hepcidin-deficiency related disorders.
Epidemiology of mental health problems among patients with cancer during COVID-19 pandemic
Authors: Wang Yuanyuan , Duan Zhizhou , Ma Zikun , Mao Yize , Li Xiyuan , Wilson Amanda , Qin Huiying , Ou Jianjun , Peng Ke , Zhou Fangjian , Li Chaofeng , Liu Zhuowei , Chen Runsen
Published: July 2020

The current study aimed to explore mental health problems in patients diagnosed with cancer during the COVID-19 pandemic. A cluster sampling, cross-sectional survey with 6213 cancer patients was conducted in one of the largest cancer centers in China. The socio-demographic and clinical characteristics, psychosomatic conditions, interpersonal relationships and social support, COVID-19 infection-related psychological stress, and mental health status were measured. Medical conditions were extracted from patients’ electronic healthcare records. Among the 6213 cancer patients, 23.4% had depression, 17.7% had anxiety, 9.3% had PTSD, and 13.5% had hostility. Hierarchical liner regression models showed that having a history of mental disorder, excessive alcohol consumption, having a higher frequency of worrying about cancer management due to COVID-19, having a higher frequency feeling of overwhelming psychological pressure from COVID-19, and having a higher level of fatigue and pain were the predominant risk factors for mental health problems in cancer patients. However, there were only 1.6% of them were seeking psychological counseling during COVID-19. We also revealed the protective factors associated with lower risk of mental health problems among cancer patients. The present study revealed a high prevalence of mental health problems and gaps in mental health services for cancer patients, which also indicated high distress from COVID-19-elevated risks. We call for systematic screening of mental health status for all cancer patients, and developing specific psychological interventions for this vulnerable population.
Stabilization of heterochromatin by CLOCK promotes stem cell rejuvenation and cartilage regeneration
Authors: Liang Chuqian , Liu Zunpeng , Song Moshi , Li Wei , Wu Zeming , Wang Zehua , Wang Qiaoran , Wang Si , Yan Kaowen , Sun Liang , Hishida Tomoaki , Cai Yanning , Belmonte Juan Carlos Izpisua , Guillen Pedro , Chan Piu , Zhou Qi , Zhang Weiqi , Qu Jing , Liu Guang-Hui
Published: July 2020

Accumulating evidence indicates an association between the circadian clock and the aging process. However, it remains elusive whether the deregulation of circadian clock proteins underlies stem cell aging and whether they are targetable for the alleviation of aging-associated syndromes. Here, we identified a transcription factor-independent role of CLOCK, a core component of the molecular circadian clock machinery, in counteracting human mesenchymal stem cell (hMSC) decay. CLOCK expression was decreased during hMSC aging. In addition, CLOCK deficiency accelerated hMSC senescence, whereas the overexpression of CLOCK, even as a transcriptionally inactive form, rejuvenated physiologically and pathologically aged hMSCs. Mechanistic studies revealed that CLOCK formed complexes with nuclear lamina proteins and KAP1, thus maintaining heterochromatin architecture and stabilizing repetitive genomic sequences. Finally, gene therapy with lentiviral vectors encoding CLOCK promoted cartilage regeneration and attenuated age-related articular degeneration in mice. These findings demonstrate a noncanonical role of CLOCK in stabilizing heterochromatin, promoting tissue regeneration, and mitigating aging-associated chronic diseases.
Modeling a potential SANS countermeasure by experimental manipulation of the translaminar pressure difference in mice
Authors: Shen Guofu , Link Schuyler S. , Tao Xiaofeng , Frankfort Benjamin J.
Published: July 2020

The spaceflight-associated neuro-ocular syndrome (SANS), which may present after prolonged exposure to microgravity, is thought to occur due to elevated intracranial pressure (ICP). Intracranial pressure interacts with intraocular pressure (IOP) to define the translaminar pressure difference (TLPD; IOP−ICP). We combined inducible models of ICP and IOP elevation in mice to interrogate the relationships among ICP, IOP, and TLPD, and to determine if IOP elevation could mitigate the phenotypes typically caused by elevated ICP and thereby serve as a countermeasure for SANS. Ten C57BL6J mice of both genders underwent experimental elevation of ICP via infusion of artificial cerebrospinal fluid into the subarachnoid space. One eye also underwent experimental elevation of IOP using the bead injection model. Intraocular pressure and ICP were monitored for 2 weeks. Optokinetic-based contrast sensitivity was measured at baseline and after 2 weeks, and post-mortem studies of optic nerve and retina anatomy were performed. Photopic contrast sensitivity was reduced more in IOP elevated than control eyes. Scotopic contrast sensitivity was reduced similarly in IOP elevated and control eyes. However, the pattern of scotopic vision loss was not uniform in IOP elevated eyes; there was minimal loss in eyes that most closely approximated the normal TLPD. Optic nerve axon loss, increased optic nerve disorganization, and retinal ganglion cell loss all occurred similarly between IOP elevated and control eyes. Elevation of IOP in eyes with elevated ICP may counterbalance some effects on vision loss but exacerbate others, suggesting complex relationships among IOP, ICP, and TLPD.
Prevalence of modifiable factors limiting treatment efficacy of poorly controlled asthma patients: EFIMERA observational study
Authors: Ribó Paula , Molina Jesús , Calle Myriam , Maiz Luis , Campo Carlos , Rytilä Paula , Plaza Vicente , Valero Antonio
Published: July 2020

Several modifiable factors leading to poor asthma control have been described. We aimed to determine the proportion of patients with inadequate treatment, adherence to it, or critical mistakes with inhaler technique, and their impact on asthma control. We conducted a cross-sectional multicenter observational study including asthma patients referred from primary to specialist care for the first time. Data collected were adequate prescription according to guidelines, treatment adherence, and disease control. Of the 1682 patients (age 45 ± 17 years, 64.6% men), 35.9% showed inadequate prescription, 76.8% low adherence, and 17% critical mistakes with inhaler technique, with significantly less critical mistakes among Easyhaler users versus other dry powder inhaler users (10.3 versus 18.4%; p < 0.05). Factors related to bad asthma control were inadequate prescription (OR: 3.65), non-adherence to treatment (OR: 1.8), and inhaler misuse (OR: 3.03). A higher number of risk factors were associated with a higher probability of having badly controlled asthma.
A cluster of metabolism-related genes predict prognosis and progression of clear cell renal cell carcinoma
Authors: Liu Mei , Pan Qiufeng , Xiao Ruihai , Yu Yi , Lu Wenbao , Wang Longwang
Published: July 2020

Clear cell renal cell carcinoma (ccRCC) has long been considered as a metabolic disease characterized by metabolic reprogramming due to the abnormal accumulation of lipid droplets in the cytoplasm. However, the prognostic value of metabolism-related genes in ccRCC remains unclear. In our study, we investigated the associations between metabolism-related gene profile and prognosis of ccRCC patients in the Cancer Genome Atlas (TCGA) database. Importantly, we first constructed a metabolism-related prognostic model based on ten genes (ALDH6A1, FBP1, HAO2, TYMP, PSAT1, IL4I1, P4HA3, HK3, CPT1B, and CYP26A1) using Lasso cox regression analysis. The Kaplan–Meier analysis revealed that our model efficiently predicts prognosis in TCGA_KIRC Cohort and the clinical proteomic tumor analysis consortium (CPTAC_ccRCC) Cohort. Using time-dependent ROC analysis, we showed the model has optimal performance in predicting long-term survival. Besides, the multivariate Cox regression analysis demonstrated our model is an independent prognostic factor. The risk score calculated for each patient was significantly associated with various clinicopathological parameters. Notably, the gene set enrichment analysis indicated that fatty acid metabolism was enriched considerably in low-risk patients. In contrast, the high-risk patients were more associated with non-metabolic pathways. In summary, our study provides novel insight into metabolism-related genes’ roles in ccRCC.
Variability of coherent and incoherent features of internal tides in the north South China Sea
Authors: Li Bingtian , Wei Zexun , Wang Xinyi , Fu You , Fu Qingjun , Li Juan , Lv Xianqing
Published: July 2020

The coherent and incoherent features of internal tides (ITs) in the north South China Sea (SCS) are investigated based on observations and numerical simulations. The 11-month (from May 2011 to March 2012) moored current observations indicate that coherent semidiurnal ITs are obviously amplified, which can be attributed to the interference of ITs. Interference enhances coherent motions of semidiurnal ITs, but weakens those of diurnal ITs. Moreover, observations also show that semidiurnal ITs are more incoherent than diurnal ITs. Variations of vertical stratification and surface tide forcing can hardly affect the incoherence of ITs. The increase of incoherent signal is largely due to the influence of mesoscale eddies. Mesoscale eddies affect both amplitude and phase of ITs, making them more incoherent. Mesoscale eddies not only increase the intensity of background currents, but also induce horizontal variations of density. Variations of horizontal density and the influence of background currents lead to the increase of incoherent signals. And semidiural ITs are more sensitive to the influence of mesoscale eddies, making them more incoherent than diurnal counterparts. Incoherent ITs, which induce strong current shear, play essential roles in cascading tidal energy to small-scale motions, and contribute to turbulent mixing eventually. The findings help to better understand ITs and may offer reference for the improvement of parameterization of ocean turbulent mixing in the northern SCS.
The education-chasing labor rush in China identified by a heterogeneous migration-network game
Authors: Zhang Xiaoqi , Zheng Yanqiao , Zhao Zhijun , Ye Xinyue , Zhang Peng , Wang Yougui , Chen Zhan
Published: July 2020

Despite persistent efforts in understanding the motives and patterns of human migration behaviors, little is known about the microscopic mechanism that drives migration and its association with migrant types. To fill the gap, we develop a population game model in which migrants are allowed to be heterogeneous and decide interactively on their destination, the resulting migration network emerges naturally as an Nash equilibrium and depends continuously on migrant features. We apply the model to Chinese labor migration data at the current and expected stages, aiming to quantify migration behavior and decision mode for different migrant groups and at different stages. We find the type-specific migration network differs significantly for migrants with different age, income and education level, and also differs from the aggregated network at both stages. However, a deep analysis on model performance suggests a different picture, stability exists for the decision mechanism behind the “as-if” unstable migration behavior, which also explains the relative invariance of low migration efficiency in different settings. Finally, by a classification of cities from the estimated game, we find the richness of education resources is the most critical determinant of city attractiveness for migrants, which gives hint to city managers in migration policy design.
Deep neural network recognition of shallow water corals in the Gulf of Eilat (Aqaba)
Authors: Raphael Alina , Dubinsky Zvy , Iluz David , Benichou Jennifer I. C. , Netanyahu Nathan S.
Published: July 2020

We describe the application of the computerized deep learning methodology to the recognition of corals in a shallow reef in the Gulf of Eilat, Red Sea. This project is aimed at applying deep neural network analysis, based on thousands of underwater images, to the automatic recognition of some common species among the 100 species reported to be found in the Eilat coral reefs. This is a challenging task, since even in the same colony, corals exhibit significant within-species morphological variability, in terms of age, depth, current, light, geographic location, and inter-specific competition. Since deep learning procedures are based on photographic images, the task is further challenged by image quality, distance from the object, angle of view, and light conditions. We produced a large dataset of over 5,000 coral images that were classified into 11 species in the present automated deep learning classification scheme. We demonstrate the efficiency and reliability of the method, as compared to painstaking manual classification. Specifically, we demonstrated that this method is readily adaptable to include additional species, thereby providing an excellent tool for future studies in the region, that would allow for real time monitoring the detrimental effects of global climate change and anthropogenic impacts on the coral reefs of the Gulf of Eilat and elsewhere, and that would help assess the success of various bioremediation efforts.
Fabrication of homotypic neural ribbons as a multiplex platform optimized for spinal cord delivery
Authors: Olmsted Zachary T. , Stigliano Cinzia , Badri Abinaya , Zhang Fuming , Williams Asher , Koffas Mattheos A. G. , Xie Yubing , Linhardt Robert J. , Cibelli Jose , Horner Philip J. , Paluh Janet L.
Published: July 2020

Cell therapy for the injured spinal cord will rely on combined advances in human stem cell technologies and delivery strategies. Here we encapsulate homotypic spinal cord neural stem cells (scNSCs) in an alginate-based neural ribbon delivery platform. We perform a comprehensive in vitro analysis and qualitatively demonstrate graft survival and injury site retention using a rat C4 hemi-contusion model. Pre-configured neural ribbons are transport-stable modules that enable site-ready injection, and can support scNSC survival and retention in vivo. Neural ribbons offer multifunctionality in vitro including co-encapsulation of the injury site extracellular matrix modifier chondroitinase ABC (chABC), tested here in glial scar models, and ability of cervically-patterned scNSCs to differentiate within neural ribbons and project axons for integration with 3-D external matrices. This is the first extensive in vitro characterization of neural ribbon technology, and constitutes a plausible method for reproducible delivery, placement, and retention of viable neural cells in vivo.
Effects of different intracranial volume correction methods on univariate sex differences in grey matter volume and multivariate sex prediction
Authors: Sanchis-Segura Carla , Ibañez-Gual Maria Victoria , Aguirre Naiara , Cruz-Gómez Álvaro Javier , Forn Cristina
Published: July 2020

Sex differences in 116 local gray matter volumes (GMVOL) were assessed in 444 males and 444 females without correcting for total intracranial volume (TIV) or after adjusting the data with the scaling, proportions, power-corrected proportions (PCP), and residuals methods. The results confirmed that only the residuals and PCP methods completely eliminate TIV-variation and result in sex-differences that are “small” (∣d∣ < 0.3). Moreover, as assessed using a totally independent sample, sex differences in PCP and residuals adjusted-data showed higher replicability ($$\approx $$≈93%) than scaling and proportions adjusted-data$$( \approx $$(≈68%) or raw data ($$\approx $$≈45%). The replicated effects were meta-analyzed together and confirmed that, when TIV-variation is adequately controlled, volumetric sex differences become “small” (∣d∣ < 0.3 in all cases). Finally, we assessed the utility of TIV-corrected/ TIV-uncorrected GMVOLfeatures in predicting individuals’ sex with 12 different machine learning classifiers. Sex could be reliably predicted (> 80%) when using raw local GMVOL, but also when using scaling or proportions adjusted-data or TIV as a single predictor. Conversely, after properly controlling TIV variation with the PCP and residuals’ methods, prediction accuracy dropped to$$\approx $$≈60%. It is concluded that gross morphological differences account for most of the univariate and multivariate sex differences in GMVOL
Peptides targeting dengue viral nonstructural protein 1 inhibit dengue virus production
Authors: Songprakhon Pucharee , Thaingtamtanha Thanawat , Limjindaporn Thawornchai , Puttikhunt Chunya , Srisawat Chatchawan , Luangaram Prasit , Dechtawewat Thanyaporn , Uthaipibull Chairat , Thongsima Sissades , Yenchitsomanus Pa-thai , Malasit Prida , Noisakran Sansanee
Published: July 2020

Viruses manipulate the life cycle in host cells via the use of viral properties and host machineries. Development of antiviral peptides against dengue virus (DENV) infection has previously been concentrated on blocking the actions of viral structural proteins and enzymes in virus entry and viral RNA processing in host cells. In this study, we proposed DENV NS1, which is a multifunctional non-structural protein indispensable for virus production, as a new target for inhibition of DENV infection by specific peptides. We performed biopanning assays using a phage-displayed peptide library and identified 11 different sequences of 12-mer peptides binding to DENV NS1. In silico analyses of peptide-protein interactions revealed 4 peptides most likely to bind to DENV NS1 at specific positions and their association was analysed by surface plasmon resonance. Treatment of Huh7 cells with these 4 peptides conjugated with N-terminal fluorescent tag and C-terminal cell penetrating tag at varying time-of-addition post-DENV infection could inhibit the production of DENV-2 in a time- and dose-dependent manner. The inhibitory effects of the peptides were also observed in other virus serotypes (DENV-1 and DENV-4), but not in DENV-3. These findings indicate the potential application of peptides targeting DENV NS1 as antiviral agents against DENV infection.
Concomitant DNA methylation and transcriptome signatures define epidermal responses to acute solar UV radiation
Authors: Holzscheck Nicholas , Söhle Jörn , Schläger Torsten , Falckenhayn Cassandra , Grönniger Elke , Kolbe Ludger , Wenck Horst , Terstegen Lara , Kaderali Lars , Winnefeld Marc , Gorges Katharina
Published: July 2020

The simultaneous analysis of different regulatory levels of biological phenomena by means of multi-omics data integration has proven an invaluable tool in modern precision medicine, yet many processes ultimately paving the way towards disease manifestation remain elusive and have not been studied in this regard. Here we investigated the early molecular events following repetitive UV irradiation of in vivo healthy human skin in depth on transcriptomic and epigenetic level. Our results provide first hints towards an immediate acquisition of epigenetic memories related to aging and cancer and demonstrate significantly correlated epigenetic and transcriptomic responses to irradiation stress. The data allowed the precise prediction of inter-individual UV sensitivity, and molecular subtyping on the integrated post-irradiation multi-omics data established the existence of three latent molecular phototypes. Importantly, further analysis suggested a form of melanin-independent DNA damage protection in subjects with higher innate UV resilience. This work establishes a high-resolution molecular landscape of the acute epidermal UV response and demonstrates the potential of integrative analyses to untangle complex and heterogeneous biological responses.
An independent validation of the kidney failure risk equation in an Asian population
Authors: Kang Min Woo , Tangri Navdeep , Kim Yong Chul , An Jung Nam , Lee Jeonghwan , Li Lilin , Oh Yun Kyu , Kim Dong Ki , Joo Kwon Wook , Kim Yon Su , Lim Chun Soo , Lee Jung Pyo
Published: July 2020

Predicting the risk of end-stage renal disease (ESRD) progression facilitates appropriate nephrology care of patients with chronic kidney disease (CKD). Previously, the kidney failure risk equations (KFREs) were developed and validated in several cohorts. The purpose of this study is to validate the KFREs in a Korean population and to recalibrate the equations. A total of 38,905 adult patients, including 13,244 patients with CKD stages G3–G5, who were referred to nephrology were recruited. Using the original KFREs (4-, 6- and 8-variable equations) and recalibration equations, we predicted the risk of 2- and 5-year ESRD progression. All analyses were conducted in CKD stages G3-G5 patients as well as the total population. In CKD stages G3–G5 patients, All the original 4-, 6- and 8-variable equations showed excellent areas under the receiver operating characteristic curve of 0.87 and 0.83 for the 2- and 5-year risk of ESRD, respectively. The results of net reclassification improvement, integrated discrimination index and Brier score showed that recalibration improved the prediction models in some cases. The original KFREs showed high discrimination in both CKD stages G3–G5 patients and the total population referred to nephrology in this large Korean cohort. KFREs can be implemented in Korean health systems and can guide nephrology referrals and other CKD-related treatment decisions.
Intermittent meromixis controls the trophic state of warming deep lakes
Authors: Lau Maximilian P. , Valerio Giulia , Pilotti Marco , Hupfer Michael
Published: July 2020

Vertical mixing modulates nutrient dynamics in lakes. However, surface warming reduces the range of vertical mixing and the probability of full circulation events. Important consequences of reduced vertical mixing include the sequestration of phosphorus (P) within a stagnant zone and the promotion of oligotrophication. Nevertheless, warming-induced shifts from full to partial mixing (meromixis) are not permanent and are partially reversible during exceptionally cold or windy winters. In this study, we investigated how intermittent meromixis affects lake P budgets. We examined the P cycle of a perialpine lake with variable mixing depths by pairing sedimentation and release flux measurements with sedimentary archives. We found that the amount of dissolved P surpassed that of the potentially mobile P in the sediments by a 13:1 ratio. At least 55% of the settled P was rapidly released to bottom waters isolated from flushing, illustrating the general biogeochemical mechanism that promotes deep-water P storage when lakes undergo warming. This storage process is abruptly inverted when meromixis suddenly retreats, deeper mixing introduces P pulses to the surface waters, thereby promoting phytoplankton proliferation. Our estimates showed that lakes containing up to 40% of the global freshwater volume could shift towards intermittent meromixis if the atmospheric warming trend continues. Thus, these lakes might accumulate 0–83% of their P load in irregularly circulating waters and are prone to large P pulses.
Anticancer properties of Tulbaghia violacea regulate the expression of p53-dependent mechanisms in cancer cell lines
Authors: Motadi Lesetja R. , Choene Mpho S. , Mthembu Nonkululeko N.
Published: July 2020

Cancer is an enormous burden of disease globally. Today, more people die from cancer than a combination of several diseases. And in females, breast and cervical malignancies remain the most common types. Currently, cervical and breast cancer are the most diagnosed gynecological cancer type amongst black females in the Southern Sahara while amongst males prostate cancer is on the upward trend. With many of them still dependent on medicinal plants as a form of therapy and the need to identify new therapeutic agents, we have identified a commonly used medicinal plant Tulbaghia violacea Harv. commonly known as Itswele lomlambo (Xhosa), wilde knoffel (Afrikaans) and Isihaqa (zulu) to evaluate its anticancer properties at a molecular biology level. In this study, we evaluated the molecular mechanism of T. violacea extracts in regulating cell death in various cancer cell lines. To achieve this, T. violacea was collected, dried before crushing into a fine ground powder. Three organic solvents namely, methanol, hexane, and butanol at 10 g per 100 mL were used as extraction solvents. Each cell line was treated with varying concentrations of the plant extract to identify the half-maximal inhibitory concentration (IC50). The IC 50 was later used to analyse if the extracts were inducing apoptosis using annexin V analysis. Furthermore, the molecular mechanisms by which apoptosis was induced was analysed by qPCR, western blots. All three extracts exhibited anticancer activity with the most cytotoxic being methanol extract. p53 expression was significantly increased in treated cells that correlated with increased caspase activity. The results point to possible activation of apoptosis following treatment with hexane extracts.
Proliferation of Aedes aegypti in urban environments mediated by the availability of key aquatic habitats
Authors: Wilke André Barretto Bruno , Vasquez Chalmers , Carvajal Augusto , Medina Johana , Chase Catherine , Cardenas Gabriel , Mutebi John-Paul , Petrie William D. , Beier John C.
Published: July 2020

Aedes aegypti is the main vector of dengue, Zika, chikungunya, and yellow fever viruses. Controlling populations of vector mosquito species in urban environments is a major challenge and being able to determine what aquatic habitats should be prioritized for controlling Ae. aegypti populations is key to the development of more effective mosquito control strategies. Therefore, our objective was to leverage on the Miami-Dade County, Florida immature mosquito surveillance system based on requested by citizen complaints through 311 calls to determine what are the most important aquatic habitats in the proliferation of Ae. aegypti in Miami. We used a tobit model for Ae. aegypti larvae and pupae count data, type and count of aquatic habitats, and daily rainfall. Our results revealed that storm drains had 45% lower percentage of Ae. aegypti larvae over the total of larvae and pupae adjusted for daily rainfall when compared to tires, followed by bromeliads with 33% and garbage cans with 17%. These results are indicating that storm drains, bromeliads and garbage cans had significantly more pupae in relation to larvae when compared to tires, traditionally know as productive aquatic habitats for Ae. aegypti. Ultimately, the methodology and results from this study can be used by mosquito control agencies to identify habitats that should be prioritized in mosquito management and control actions, as well as to guide and improve policies and increase community awareness and engagement. Moreover, by targeting the most productive aquatic habitats this approach will allow the development of critical emergency outbreak responses by directing the control response efforts to the most productive aquatic habitats.
Physical and mechanical properties of wood and their geographic variations in Larix sibirica trees naturally grown in Mongolia
Authors: Tumenjargal Bayasaa , Ishiguri Futoshi , Aiso Haruna , Takahashi Yusuke , Nezu Ikumi , Takashima Yuya , Baasan Bayartsetseg , Chultem Ganbaatar , Ohshima Jyunichi , Yokota Shinso
Published: July 2020

We examined the physical and mechanical properties of wood in Siberian larch (Larix sibirica) trees that grow naturally in five Mongolian provenances (Khentii, Arkhangai, Zavkhan, Khuvsgul, and Selenge) and the geographic variations between them. Five trees with stem diameters of 20 to 30 cm at 1.3 m above ground were collected from each provenance. The mean values of the modulus of elasticity (MOE), modulus of rupture (MOR), compressive strength parallel to grain (CS), and shearing strength (SS) ranged from 7.03 to 9.51 GPa, 79.8 to 103.9 MPa, 46.3 to 51.1 MPa, and 10.4 to 13.0 MPa, respectively. Significant differences were found in radial and tangential shrinkage, MOE, MOR, and SS in wood among the five provenances. In addition, juvenile wood had inferior physical and mechanical properties in comparison to mature wood within and among provenances. Furthermore, there were significant differences in all examined properties, except for CS, in mature wood among the five provenances. Higher correlation coefficients were also obtained in mature wood among all mechanical properties, except for SS.
A robust convolutional neural network for lung nodule detection in the presence of foreign bodies
Authors: Schultheiss Manuel , Schober Sebastian A. , Lodde Marie , Bodden Jannis , Aichele Juliane , Müller-Leisse Christina , Renger Bernhard , Pfeiffer Franz , Pfeiffer Daniela
Published: July 2020

Lung cancer is a major cause of death worldwide. As early detection can improve outcome, regular screening is of great interest, especially for certain risk groups. Besides low-dose computed tomography, chest X-ray is a potential option for screening. Convolutional network (CNN) based computer aided diagnosis systems have proven their ability of identifying nodules in radiographies and thus may assist radiologists in clinical practice. Based on segmented pulmonary nodules, we trained a CNN based one-stage detector (RetinaNet) with 257 annotated radiographs and 154 additional radiographs from a public dataset. We compared the performance of the convolutional network with the performance of two radiologists by conducting a reader study with 75 cases. Furthermore, the potential use for screening on patient level and the impact of foreign bodies with respect to false-positive detections was investigated. For nodule location detection, the architecture achieved a performance of 43 true-positives, 26 false-positives and 22 false-negatives. In comparison, performance of the two readers was 42 ± 2 true-positives, 28 ± 0 false-positives and 23 ± 2 false-negatives. For the screening task, we retrieved a ROC AUC value of 0.87 for the reader study test set. We found the trained RetinaNet architecture to be only slightly prone to foreign bodies in terms of misclassifications: out of 59 additional radiographs containing foreign bodies, false-positives in two radiographs were falsely detected due to foreign bodies.
Transient neonatal antibiotic exposure increases susceptibility to late-onset sepsis driven by microbiota-dependent suppression of type 3 innate lymphoid cells
Authors: Niu Xinying , Daniel Sarah , Kumar Dharmendra , Ding Elizabeth Y. , Savani Rashmin C. , Koh Andrew Y. , Mirpuri Julie
Published: July 2020

Extended early antibiotic exposure in the neonatal intensive care unit is associated with an increased risk for the development of late-onset sepsis (LOS). However, few studies have examined the mechanisms involved. We sought to determine how the neonatal microbiome and intestinal immune response is altered by transient early empiric antibiotic exposure at birth. Neonatal mice were transiently exposed to broad-spectrum antibiotics from birth for either 3- (SE) or 7-days (LE) and were examined at 14-days-old. We found that mice exposed to either SE or LE showed persistent expansion of Proteobacteria (2 log difference, P < 0.01). Further, LE mice demonstrated baseline translocation of E. coli into the liver and spleen and were more susceptible K. pneumoniae-induced sepsis. LE mice had a significant and persistent decrease in type 3 innate lymphoid cells (ILC3) in the lamina propria. Reconstitution of the microbiome with mature microbiota by gavage in LE mice following antibiotic exposure resulted in an increase in ILC3 and partial rescue from LOS. We conclude that prolonged exposure to broad spectrum antibiotics in the neonatal period is associated with persistent alteration of the microbiome and innate immune response resulting in increased susceptibility to infection that may be partially rescued by microbiome reconstitution.
Positional determination of the carbon–carbon double bonds in unsaturated fatty acids mediated by solvent plasmatization using LC–MS
Authors: Takashima Shigeo , Toyoshi Kayoko , Yamamoto Takuhei , Shimozawa Nobuyuki
Published: July 2020

Fatty acids (FAs) are the central components of life: they constitute biological membranes in the form of lipid, act as signaling molecules, and are used as energy sources. FAs are classified according to their chain lengths and the number and position of carbon–carbon double bond, and their physiological character is largely defined by these structural properties. Determination of the precise structural properties is crucial for characterizing FAs, but pinpointing the exact position of carbon–carbon double bond in FA molecules is challenging. Herein, a new analytical method is reported for determining the double bond position of mono- and poly-unsaturated FAs using liquid chromatography-mass spectrometry (LC–MS) coupled with solvent plasmatization. With the aid of plasma on ESI capillary, epoxidation or peroxidation of carbon–carbon double bond in FAs is facilitated. Subsequently, molecular fragmentation occurs at or beside the epoxidized or peroxidized double bond via collision-induced dissociation (CID), and the position of the double bond is elucidated. In this method, FAs are separated by LC, modified by plasma, fragmented via CID, and detected using a time-of-flight mass spectrometer in a seamless manner such that the FA composition in a mixture can be determined. Our method enables thorough characterization of FA species by distinguishing multiple isomers, and therefore can uncover the true diversity of FAs for their application in food, health, and medical sciences.
Author Correction: Ocular biometry and refractive outcomes using two swept-source optical coherence tomography-based biometers with segmental or equivalent refractive indices
Authors: Omoto Miki Kamikawatoko , Torii Hidemasa , Masui Sachiko , Ayaki Masahiko , Tsubota Kazuo , Negishi Kazuno
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Population-specific signatures of intra-individual mitochondrial DNA heteroplasmy and their potential evolutionary advantages
Authors: Tikochinski Yaron , Carreras Carlos , Tikochinski Gili , Vilaça Sibelle T.
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
In-silico study of the cardiac arrhythmogenic potential of biomaterial injection therapy
Authors: Ramírez William A. , Gizzi Alessio , Sack Kevin L. , Guccione Julius M. , Hurtado Daniel E.
Published: July 2020

Biomaterial injection is a novel therapy to treat ischemic heart failure (HF) that has shown to reduce remodeling and restore cardiac function in recent preclinical studies. While the effect of biomaterial injection in reducing mechanical wall stress has been recently demonstrated, the influence of biomaterials on the electrical behavior of treated hearts has not been elucidated. In this work, we developed computational models of swine hearts to study the electrophysiological vulnerability associated with biomaterial injection therapy. The propagation of action potentials on realistic biventricular geometries was simulated by numerically solving the monodomain electrophysiology equations on anatomically-detailed models of normal, HF untreated, and HF treated hearts. Heart geometries were constructed from high-resolution magnetic resonance images (MRI) where the healthy, peri-infarcted, infarcted and gel regions were identified, and the orientation of cardiac fibers was informed from diffusion-tensor MRI. Regional restitution properties in each case were evaluated by constructing a probability density function of the action potential duration (APD) at different cycle lengths. A comparative analysis of the ventricular fibrillation (VF) dynamics for every heart was carried out by measuring the number of filaments formed after wave braking. Our results suggest that biomaterial injection therapy does not affect the regional dispersion of repolarization when comparing untreated and treated failing hearts. Further, we found that the treated failing heart is more prone to sustain VF than the normal heart, and is at least as susceptible to sustained VF as the untreated failing heart. Moreover, we show that the main features of VF dynamics in a treated failing heart are not affected by the level of electrical conductivity of the biogel injectates. This work represents a novel proof-of-concept study demonstrating the feasibility of computer simulations of the heart in understanding the arrhythmic behavior in novel therapies for HF.
Synchronization of two cavity-coupled qubits measured by entanglement
Authors: Huan Tian-tian , Zhou Ri-gui , Ian Hou
Published: July 2020

Some nonlinear radiations such as superfluorescence can be understood as cooperative effects between atoms. We regard cooperative radiations as a manifested effect secondary to the intrinsic synchronization among the two-level atoms and propose the entanglement measure, concurrence, as a time-resolved measure of synchronization. Modeled on two cavity-coupled qubits, the evolved concurrence monotonically increases to a saturated level. The finite duration required for the rising to saturation coincides with the time delay characteristic to the initiation of superfluorescence, showing the role of synchronization in establishing the cooperation among the qubits. We verify concurrence to be a good measure of synchronization by comparing it with asynchronicity computed from the difference between the density matrices of the qubits. We find that the feature of time delay agrees in both measures and is determined by the coupling regimes of the cavity-qubit interaction. Specifically, synchronization is impossible in the weak coupling regime.
Nearly-incompressible transverse isotropy (NITI) of cornea elasticity: model and experiments with acoustic micro-tapping OCE
Authors: Pitre John J. , Kirby Mitchell A. , Li David S. , Shen Tueng T. , Wang Ruikang K. , O’Donnell Matthew , Pelivanov Ivan
Published: July 2020

The cornea provides the largest refractive power for the human visual system. Its stiffness, along with intraocular pressure (IOP), are linked to several pathologies, including keratoconus and glaucoma. Although mechanical tests can quantify corneal elasticity ex vivo, they cannot be used clinically. Dynamic optical coherence elastography (OCE), which launches and tracks shear waves to estimate stiffness, provides an attractive non-contact probe of corneal elasticity. To date, however, OCE studies report corneal moduli around tens of kPa, orders-of-magnitude less than those (few MPa) obtained by tensile/inflation testing. This large discrepancy impedes OCE’s clinical adoption. Based on corneal microstructure, we introduce and fully characterize a nearly-incompressible transversely isotropic (NITI) model depicting corneal biomechanics. We show that the cornea must be described by at least two shear moduli, contrary to current single-modulus models, decoupling tensile and shear responses. We measure both as a function of IOP in ex vivo porcine cornea, obtaining values consistent with both tensile and shear tests. At pressures above 30 mmHg, the model begins to fail, consistent with non-linear changes in cornea at high IOP.
Sex-dependent associations of low birth weight and suicidal ideation in adulthood: a community-based cohort study
Authors: Ernst Mareike , Reiner Iris , Fieß Achim , Tibubos Ana N. , Schulz Andreas , Burghardt Juliane , Klein Eva M. , Brähler Elmar , Wild Philipp S. , Münzel Thomas , König Jochem , Lackner Karl J. , Pfeiffer Norbert , Michal Matthias , Wiltink Jörg , Beutel Manfred E.
Published: July 2020

Low birth weight (LBW; < 2,500 g) has been identified as a risk factor for adverse mental health outcomes over the life span. However, little is known about the association of LBW and suicidal ideation in middle and late adulthood. We investigated N = 8,278 participants of a representative community cohort: 3,849 men (46.5%) and 4,429 women (53.5%) (35–74 years of age). We assessed standardized measures of mental distress, sociodemographics, health behavior, and somatic factors (based on an extensive medical assessment). Controlling for these confounders, we examined the relationship of birth weight and suicidal ideation in logistic regression models. As men and women differ with regard to their susceptibility to suicidal ideation and behavior, we tested sex-dependent effects. LBW was reported by 458 participants (5.5%). In men, LBW was associated with a higher likelihood of reporting suicidal ideation (OR 2.92, 95% CI 1.58–5.12). In women, there was no such relationship. The findings underscore the interrelatedness of the physical and psychological domain, the role of early adversity in suicidal ideation, and they identify a vulnerable group whose numbers are expected to grow. They also indicate other risk factors for suicidal ideation in the community (mental distress, lack of social support, and health risk behavior).
Glucose unit index (GUI) of permethylated glycans for effective identification of glycans and glycan isomers
Authors: Gautam Sakshi , Peng Wenjing , Cho Byeong Gwan , Huang Yifan , Banazadeh Alireza , Yu Aiying , Dong Xue , Mechref Yehia
Published: July 2020

Retention time normalization of permethylated glycans and glycan isomers across different instruments and laboratories, using standard dextrin ladder. (Figure created with BioRender.com).
In situgrowth of nano-gold on anodized aluminum oxide with tandem nanozyme activities towards sensitive electrochemical nanochannel sensing
Authors: Xia Xin , Li Hui , Zhou Guoxing , Ge Lei , Li Feng
Published: July 2020

The growth of nano-gold tandem nanozymes on anodized aluminum oxide is successfully developed using poly-dopamine as anin situreducing layer for electrochemical nanochannel sensing.
The development of a Glypican-3-specific binding peptide usingin vivoandin vitrotwo-step phage display screening for the PET imaging of hepatocellular carcinoma
Authors: Qin Yushuang , Cheng Siyuan , Li Yesen , Zou Sijuan , Chen Minglong , Zhu Dongling , Gao Shi , Wu Hua , Zhu Lei , Zhu Xiaohua
Published: July 2020

Anin vivoandin vitrotwo-step phage display screening approach to identify Glypican-3 targeting peptides for the detection of hepatocellular carcinoma with low normal liver uptake.
Dendritic cell immune potency on 2D and in 3D collagen matrices
Authors: Sapudom Jiranuwat , Alatoom Aseel , Mohamed Walaa K. E. , Garcia-Sabaté Anna , McBain Ian , Nasser Rasha A. , Teo Jeremy C. M.
Published: July 2020

Dendritic cell immune potency from two immunologically relevant perspectives is modulated by cell culture dimensionality and collagen matrix density.
Partial S substitution activates NiMoO4 for efficient and stable electrocatalytic urea oxidation
Authors: Han Wen-Kai , Li Xiao-Peng , Lu Li-Na , Ouyang Ting , Xiao Kang , Liu Zhao-Qing
Published: July 2020

Achieving a profound understanding of the reaction kinetics of a catalyst by modulating its electronic structure is significant.
Crystal engineering of porous coordination networks to enable separation of C2 hydrocarbons
Authors: Mukherjee Soumya , Sensharma Debobroto , Chen Kai-Jie , Zaworotko Michael J.
Published: July 2020

Diverse crystal engineering principles employed in the discovery of porous coordination networks for the selective separation of C2 gases reveal that control of pore size and pore chemistry emerges as the key to unlock their outstanding performances.
Design of superatomic systems: exploiting favourable conditions for the delocalisation of d-electron density in transition metal doped clusters
Authors: Gilmour J. T. A. , Gaston N.
Published: July 2020

Some transition metal atoms are able to contribute all of their d-electrons into a global electronic structure, when the conditions are favourable for the closure of superatomic shells.
Small crowder interactions can drive hydrophobic polymer collapse as well as unfolding
Authors: Nayar Divya
Published: July 2020

The strength of polymer–crowder attractions determine polymer collapse or unfolding. Collapse may occur via preferential depletion or adsorption of crowders.
A theoretical strategy for pressure-driven ferroelectric transition associated with critical behavior and magnetoelectric coupling in organic multiferroics
Authors: Ding L. J. , Zhong Y.
Published: July 2020

The pressure-driven ferroelectric transition with Tc ∼ (p − pc)1/2 and Tc–p linear relationships is revealed, in accordance with the experimental observation.
Preparation of AuPd/ZnO–CuO for the directional oxidation of glycerol to DHA
Authors: Zhao Gengqiang , Wu Guandong , Liu Yanan , He Yufei , Feng Junting , Li Dianqing
Published: July 2020

Under alkali-free conditions, 86% DHA selectivity and 65% DHA yield were achieved in the selective oxidation of glycerol.
Significantly enhanced Pb resistance of a Co-modified Mn–Ce–Ox/TiO2 catalyst for low-temperature NH3-SCR of NOx
Authors: Li Gehua , Mao Dongsen , Chao Mengxi , Li Gang , Yu Jun , Guo Xiaoming
Published: July 2020

Co modification can significantly improve the performance for low-temperature NH3-SCR of NOx and the Pb resistance of the Mn–Ce–Ox/TiO2 catalyst.
Re–Silane complexes as frustrated lewis pairs for catalytic hydrosilylation
Authors: Brown Caleb A. , Abrahamse Michael , Ison Elon A.
Published: July 2020

A pathway for the catalytic hydrosilylation of carbonyl substrates was calculated by DFT(B3PW91-D3) for both cationic and neutral Re(iii) species. This mechanism is similar to the pathway calculated for M(C6F5)3 (M = B, Al and Ga) catalysts.
Improving the bioaccessibility and bioavailability of carnosic acid using a lecithin-based nanoemulsion: complementary in vitro and in vivo studies
Authors: Zheng Huijuan , Wijaya Wahyu , Zhang Hongwei , Feng Konglong , Liu Qianru , Zheng Ting , Yin Zhiya , Cao Yong , Huang Qingrong
Published: July 2020

Nanoemulsion with good physical stability can enhance the oral bioaccessibility and bioavailability of carnosic acid demonstrated by in vitro digestion models and in vivo pharmacokinetic studies using an animal model.