bluuebunny/crossref_metadata_2025 huggingface dataset:
Prenatal Diagnosis of 8p23 Deletion Syndrome by Single Nucleotide Polymorphism Microarray
Authors: Kaymak Didem , Alpay Verda , Başıbüyük Zafer , Davutoğlu Ebru Alıcı , Madazlı Riza
Published: October 2021

8p23 deletion syndrome is characterized by congenital heart disease, diaphragmatic hernia, growth restriction, microcephaly, intellectual disability, behavioral problems, and abnormal genitalia. Prenatal findings are generally related to abnormal ultrasound findings and few cases have been reported in the literature. We present the prenatal diagnosis of 8p23 deletion syndrome with sonographic features of fetal growth restriction, short long bones, increased right ventricular wall thickness and small ventricular dimensions without an obvious structural fetal heart anomaly. The deletion size of the present case was one of the largest reported prenatally with a 10.8 MB deletion in the 8p23.3p23.1 region that did not include the critical GATA4 gene. The large deletion in our case included the SOX7, Tankyrase 1 (TNKS) and Microcephalin 1 (MCPH 1) genes. We assume that classical phenotypic features of micrognathia, low-set ears, flat and broad nasal bridge that we observed in our case may be due to these deletions. Microarray analysis of the chromosomes should be performed to diagnose chromosome aberrations such as 8p23 deletion syndrome in obscure ultrasonographic findings prenatally.
Production and Subsequent Forming of Chip-Based Aluminium Sheets Without Remelting
Authors: Schulze André , Hering Oliver , Tekkaya A. Erman
Published: October 2021

Bent components and deep drawn cups are produced by direct usage of aluminium chips without melting following a new process chain: hot extrusion of aluminium chips to a cylindrical open profile, flattening, subsequent rolling and bending or deep drawing. The properties of the hot extruded chip-based AA6060 sheets are examined by tensile tests and microstructural investigations and the results are compared with those obtained from material extruded from conventional cast billets. The chip-based sheets were used to form components by bending or deep drawing. No significant differences between the bent components or deep-drawn cups made of chips and those from cast material are observed regarding their capability for further plastic forming operations. This makes the new process route a resource-efficient alternative for the production of aluminium sheet products.
Categorizing white blood cells by utilizing deep features of proposed 4B-AdditionNet-based CNN network with ant colony optimization
Authors: Shahzad Asim , Raza Mudassar , Shah Jamal Hussain , Sharif Muhammad , Nayak Ramesh Sunder
Published: October 2021

White blood cells, WBCs for short, are an essential component of the human immune system. These cells are our body's first line of defense against infections and diseases caused by bacteria, viruses, and fungi, as well as abnormal and external substances that may enter the bloodstream. A wrong WBC count can signify dangerous viral infections, autoimmune disorders, cancer, sarcoidosis, aplastic anemia, leukemia, tuberculosis, etc. A lot of these diseases and disorders can be extremely painful and often result in death. Leukemia is among the more common types of blood cancer and when left undetected leads to death. An early diagnosis is necessary which is possible by looking at the shapes and determining the numbers of young and immature WBCs to see if they are normal or not. Performing this task manually is a cumbersome, expensive, and time-consuming process for hematologists, and therefore computer-aided systems have been developed to help with this problem. This paper proposes an improved method of classification of WBCs utilizing a combination of preprocessing, convolutional neural networks (CNNs), feature selection algorithms, and classifiers. In preprocessing, contrast-limited adaptive histogram equalization (CLAHE) is applied to the input images. A CNN is designed and trained to be used for feature extraction along with ResNet50 and EfficientNetB0 networks. Ant colony optimization is used to select the best features which are then serially fused and passed onto classifiers such as support vector machine (SVM) and quadratic discriminant analysis (QDA) for classification. The classification accuracy achieved on the Blood Cell Images dataset is 98.44%, which shows the robustness of the proposed work.
Design of an unmanned aircraft system for high-altitude 1 kW fuel cell power system
Authors: Reid William A. , Albayati Ibrahim M.
Published: October 2021

A proton exchange membrane (PEM) fuel cell is particularly considered as a prime power supply for a fuel cell-powered unmanned aircraft system (UAS) as it possesses a very high-power density in comparison with other fuel cell types, hence a high potential to be used for high altitude long endurance (HALE) UAS flights. This paper will focus on examining the design requirements for the UAS-based 1 kW PEM fuel cell for high altitude operation (10–11 km), which can be correlated into a quantitative data to produce a design constraints diagram. The maximum take-off mass, endurance, and geometries for potential UAS design are estimated. Four different geometrical design profiles are developed and presented. The resulting geometries are analysed and the design parameters of the estimated 1 kW design yielded an aircraft of maximum take-off mass 34.8 kg, wingspan of 10.4 m, cruising speed 20 m/s, stall speed 11.23 m/s, and maximum endurance of 4 h. The constraint diagram deploys these assumptions as well as values generated through the design calculations to form a possible design of which the 1 kW UAS falls slightly outside of the possible design space; this is due to the minimum thrust-to-weight ratio required to achieve the desired service ceiling; however, further alterations and adjustments on the design and mission requirements are provided to place the design of the UAS within the possible design space.
Distributional effects of technological regime changes: hysteresis, concentration and inequality dynamics
Authors: Dawid Herbert , Hepp Jasper
Published: October 2021

In this paper, we study the effect of different types of technological regime changes on the evolution of industry concentration and wage inequality. Using a calibrated agent-based macroeconomic framework, the Eurace@Unibi model, we consider scenarios where the new regime is characterized by a finite time period of more frequent respectively more substantial changes in the frontier technology compared to the old regime. We show that under both scenarios, the regime change leads to an increase in the heterogeneity of productivity in the firm population and to increased market concentration, where effects are much less pronounced if the new regime differs from the old one with respect to the frequency of innovations. If the new regime is characterized by an increase of the size of the frontier jumps along the technological trajectory, the evolution of the wage inequality has an inverted U-shape with a large fraction of workers profiting in the very long run from high wages offered by dominant high-tech firms. Finally, it is shown that (observable) heterogeneity of worker skills plays an important role in generating these dynamic effects of technological regime changes.
Reductions in inpatient fluoroquinolone use and postdischarge Clostridioides difficile infection (CDI) from a systemwide antimicrobial stewardship intervention
Authors: Jones K. Ashley , Onwubiko Udodirim N. , Kubes Julianne , Albrecht Benjamin , Paciullo Kristen , Howard-Anderson Jessica , Suchindran Sujit , Trible Ronald , Jacob Jesse T. , Yi Sarah H. , Goodenough Dana , Fridkin Scott K. , Sexton Mary Elizabeth , Wiley Zanthia
Published: October 2021

Objective:

To determine the impact of an inpatient stewardship intervention targeting fluoroquinolone use on inpatient and postdischarge Clostridioides difficile infection (CDI).

Design:

We used an interrupted time series study design to evaluate the rate of hospital-onset CDI (HO-CDI), postdischarge CDI (PD-CDI) within 12 weeks, and inpatient fluoroquinolone use from 2 years prior to 1 year after a stewardship intervention.

Setting:

An academic healthcare system with 4 hospitals.

Patients:

All inpatients hospitalized between January 2017 and September 2020, excluding those discharged from locations caring for oncology, bone marrow transplant, or solid-organ transplant patients.

Intervention:

Introduction of electronic order sets designed to reduce inpatient fluoroquinolone prescribing.

Results:

Among 163,117 admissions, there were 683 cases of HO-CDI and 1,104 cases of PD-CDI. In the context of a 2% month-to-month decline starting in the preintervention period (P < .01), we observed a reduction in fluoroquinolone days of therapy per 1,000 patient days of 21% after the intervention (level change, P < .05). HO-CDI rates were stable throughout the study period. In contrast, we also detected a change in the trend of PD-CDI rates from a stable monthly rate in the preintervention period to a monthly decrease of 2.5% in the postintervention period (P < .01).

Conclusions:

Our systemwide intervention reduced inpatient fluoroquinolone use immediately, but not HO-CDI. However, a downward trend in PD-CDI occurred. Relying on outcome measures limited to the inpatient setting may not reflect the full impact of inpatient stewardship efforts.
Decision support system for flood risk reduction policies: The case of a flood protection measure in the area of Vicenza
Authors: Pantalona Georgia , Tsalakanidou Filareti , Nikolopoulos Spiros , Kompatsiaris Ioannis , Lombardo Francesca , Norbiato Daniele , Ferri Michele , Kovats Laszlo , Haberstock Holger
Published: October 2021

Climate change is one of the most significant and pressing issues faced by humanity; it frequently results in major natural disasters, such as catastrophic floods, which require the establishment of effective management policies by local and national authorities. These policies involve complex multistep decision-making processes that require combined assessment of various sources of data by different stakeholders. Even though an abundance of data is being collected to monitor climate change and estimate its consequences on the society, the environment, and the economy, policy-making is still largely based on intuition rather than evidence due to lack of a structured approach for modeling the decision-making process and considering the appropriate use of data in every step of the process. The goal of this work is to introduce a novel decision support system that can guide policy makers through a structured data-driven decision-making process aiming to create policies for flood risk management. The proposed system is a multifacet platform that guides policy makers through five phases—inform, advise, monitor, evaluate, and revise—of the policy cycle. For each phase, different dashboards provide relevant information regarding the environmental, social, and economic conditions. To demonstrate the potential of the proposed system, we use it to assess a flood protection policy in the city of Vicenza, Italy. The results reveal the benefits and challenges of the proposed decision support tool for public administrations involved in flood risk management.
Necrotising otitis externa and how to reduce length of hospital stay: a complete audit cycle of 77 hospital admissions
Authors: Mohammed H , Chean Khun Ng J , Qureshi M H , Yates P
Published: October 2021

Background

Necrotising otitis externa is a serious condition that requires hospital admission. Longer hospital stays are associated with increased complications.

Method

This was a closed audit cycle in a tertiary ENT centre of patients presenting with necrotising otitis externa to the ENT department between 2015 and 2019. The aim was to audit the length of hospital stay in comparison to national figures as well as the time needed for investigations.

Results

The number of patients with necrotising otitis externa is increasing in England. Length of stay, however, appears to be more stable. A total of 66 admissions occurred over the study period for 48 patients in total, and mean length of stay was 12.4 days. After implementation of a new protocol, length of stay was reduced to 7.1 days.

Conclusion

Patients with necrotising otitis externa require prompt diagnosis and management in order to shorten length of stay in hospital and avoid serious complications. Multi-disciplinary protocol development and implementation could help in reducing length of stay of necrotising otitis externa patients.
Stigmatization of Voluntarily Childfree Women and Men in the	UK
Authors: Ekelund Malin , Ask Karl
Published: October 2021

Abstract. People who choose not to have children may face negative social judgment. Using a UK sample, Study 1 ( N = 199) successfully replicated Ashburn-Nardo’s (2017) finding that childfree targets are perceived as less psychologically fulfilled than targets with children. The effect, however, appeared limited to expected decision regret rather than general fulfillment, which was later confirmed in Study 2 ( N = 329). In contrast to Ashburn-Nardo , our results did not indicate that moral outrage mediates the effect (Study 1), but exploratory findings suggested that perceivers who intend to have children of their own perceive the childfree as morally inferior and less likable (Study 2). Participants’ endorsement of conservative values was not consistently related to negative perceptions of childfree targets.
Slow Slip Triggers the 2018 Mw 6.9 Zakynthos Earthquake Within the Weakly Locked Hellenic Subduction System, Greece
Authors: Saltogianni Vasso , Mouslopoulou Vasiliki , Dielforder Armin , Bocchini Gian Maria , Bedford Jonathan , Oncken Onno
Published: October 2021

Slow slip events (SSEs) at subduction zones can precede large‐magnitude earthquakes and may serve as precursor indicators, but the triggering of earthquakes by slow slip remains insufficiently understood. Here, we combine geodetic, Coulomb wedge and Coulomb failure‐stress models with seismological data to explore the potential causal relationship between two SSEs and the 2018 Mw 6.9 Zakynthos Earthquake within the Hellenic Subduction System. We show that both SSEs released up to 10 mm of aseismic slip on the plate‐interface and were accompanied by an increase in upper‐plate seismicity rate. While the first SSE in late 2014 generated only mild Coulomb failure stress changes (≤3 kPa), that were nevertheless sufficient to destabilize faults of various kinematics in the overriding plate, the second SSE in 2018 caused stress changes up to 25 kPa prior to the mainshock. Collectively, these stress changes affected a highly overpressured and mechanically weak forearc, whose state of stress fluctuated between horizontal deviatoric compression and tension during the years preceding the Zakynthos Earthquake. We conclude that this configuration facilitated episodes of aseismic and seismic deformation that ultimately triggered the Zakynthos Earthquake.
A Spherical Harmonic Model of Earth's Lithospheric Magnetic Field up to Degree 1050
Authors: Thébault E. , Hulot G. , Langlais B. , Vigneron P.
Published: October 2021

Detailed mapping of the Earth's magnetic field brings key constraints on the composition, dynamics, and history of the crust. Satellite and near‐surface measurements detect different length scales and are complementary. Here, we build a model, selecting and processing magnetic field measurements from the German CHAMP and ESA Swarm satellites, which we merge with near‐surface scalar anomaly data. We follow a regional approach for modeling the magnetic field measurements and next transform the series of regional models into a unique set of spherical harmonic (SH) Gauss coefficients. This produces the first global model to SH degree 1050 derived by inversion of all available measurements. The new model agrees with previous satellite‐based models at large wavelengths and fits the CHAMP and Swarm satellite data down to expected noise levels. Further assessment in the geographical and spectral domains shows the model to be stable when downward continued to the Earth's surface.
Carbon Dioxide and Methane Release Following Abrupt Thaw of Pleistocene Permafrost Deposits in Arctic Siberia
Authors: Knoblauch Christian , Beer Christian , Schuett Alexander , Sauerland Lewis , Liebner Susanne , Steinhof Axel , Rethemeyer Janet , Grigoriev Mikhail N. , Faguet Alexey , Pfeiffer Eva‐Maria
Published: October 2021

The decomposition of thawing permafrost organic matter (OM) to the greenhouse gases (GHG) carbon dioxide (CO2) and methane forms a positive feedback to global climate change. Data on in situ GHG fluxes from thawing permafrost OM are scarce and OM degradability is largely unknown, causing high uncertainties in the permafrost‐carbon climate feedback. We combined in situ CO2 and methane flux measurements at an abrupt permafrost thaw feature with laboratory incubations and dynamic modeling to quantify annual CO2 release from thawing permafrost OM, estimate its in situ degradability and evaluate the explanatory power of incubation experiments. In July 2016 and 2019, CO2 fluxes ranged between 0.24 and 2.6 g CO2‐C m−2 d−1. Methane fluxes were low, which coincided with the absence of active methanogens in the Pleistocene permafrost. CO2 fluxes were lower three years after initial thaw after normalizing these fluxes to thawed carbon, indicating the depletion of labile carbon. Higher CO2 fluxes from thawing Pleistocene permafrost than from Holocene permafrost indicate OM preservation for millennia and give evidence that microbial activity in the permafrost was not substantial. Short‐term incubations overestimated in situ CO2 fluxes but underestimated methane fluxes. Two independent models simulated median annual CO2 fluxes of 160 and 184 g CO2‐C m−2 from the thaw slump, which include 25%–31% CO2 emissions during winter. Annual CO2 fluxes represent 0.8% of the carbon pool thawed in the surface soil. Our results demonstrate the potential of abrupt thaw processes to transform the tundra from carbon neutral into a substantial GHG source.
Streams as Mirrors: Reading Subsurface Water Chemistry From Stream Chemistry
Authors: Stewart Bryn , Shanley James B. , Kirchner James W. , Norris David , Adler Thomas , Bristol Caitlin , Harpold Adrian A. , Perdrial Julia N. , Rizzo Donna M. , Sterle Gary , Underwood Kristen L. , Wen Hang , Li Li
Published: October 2021

The shallow and deep hypothesis suggests that stream concentration‐discharge (CQ) relationships are shaped by distinct source waters from different depths. Under this hypothesis, baseflows are typically dominated by groundwater and mostly reflect groundwater chemistry, whereas high flows are typically dominated by shallow soil water and mostly reflect soil water chemistry. Aspects of this hypothesis draw on applications like end member mixing analyses and hydrograph separation, yet direct data support for the hypothesis remains scarce. This work tests the shallow and deep hypothesis using co‐located measurements of soil water, groundwater, and streamwater chemistry at two intensively monitored sites, the W‐9 catchment at Sleepers River (Vermont, United States) and the Hafren catchment at Plynlimon (Wales). At both sites, depth profiles of subsurface water chemistry and stream CQ relationships for the 10 solutes analyzed are broadly consistent with the hypothesis. Solutes that are more abundant at depth (e.g., calcium) exhibit dilution patterns (concentration decreases with increasing discharge). Conversely, solutes enriched in shallow soils (e.g., nitrate) generally exhibit flushing patterns (concentration increases with increasing discharge). The hypothesis may hold broadly true for catchments that share such biogeochemical stratifications in the subsurface. Soil water and groundwater chemistries were estimated from high‐ and low‐flow stream chemistries with average relative errors ranging from 24% to 82%. This indicates that streams mirror subsurface waters: stream chemistry can be used to infer scarcely measured subsurface water chemistry, especially where there are distinct shallow and deep end members.
The Upper Tail of Flood Peaks Over China: Hydrology, Hydrometeorology, and Hydroclimatology
Authors: Yang Long , Yang Yixin , Smith James
Published: October 2021

Characterizing the upper tail of flood peak distributions remains a challenge due to the elusive nature of extreme floods. China has experienced some of the most extreme floods on Earth and is therefore an important setting for extreme flood research. Here, we examine the upper tail of flood peaks over China based on a comprehensive flood dataset that integrates systematic observations from 1759 stream gaging stations and 14,779 historical flood surveys. Floods with large upper tail ratios (i.e., flood peak discharge normalized by sample 10‐yr flood) cluster spatially in the windward regions of mountainous terrain with basin mean annual rainfall of around 550 mm. Large upper tail ratio floods are associated with a mixture of rainfall generation processes. These processes are characterized by anomalous moisture transport (e.g., zonal water vapor pathways) and/or synoptic configurations (e.g., blocking), with respect to flood‐producing storms for annual flood peaks. Downscaling simulations with the Weather Research and Forecasting model for the 1939, 1963, and 2016 floods over the North China Plain region highlight the role of interactions between complex terrain and large‐scale environment in defining the world envelope curve of flood peaks. The upper‐tail floods demonstrate a combination of ingredients producing extreme rainfall. Our results provide important insights to extreme floods in China and a frame of reference for assessing the largest floods on Earth.
Role of GALNT4 in protecting against cardiac hypertrophy through ASK1 signaling pathway
Authors: Zhang Bin-Bin , Gao Lu , Yang Qin , Liu Yuan , Yu Xiao-Yue , Shen Ji-Hong , Zhang Wen-Cai , Han Zhan-Ying , Chen Shao-Ze , Guo Sen
Published: October 2021

Pathological myocardial hypertrophy is regulated by multiple pathways. However, its underlying pathogenesis has not been fully explored. The goal of this work was to elucidate the function of polypeptide N-acetylgalactosaminyltransferase 4 (GALNT4) in myocardial hypertrophy and its underlying mechanism of action. We illustrated that GALNT4 was upregulated in the models of hypertrophy. Two cardiac hypertrophy models were established through partial transection of the aorta in GALNT4-knockout (GALNT4-KO) mice and adeno-associated virus 9-GALNT4 (AAV9-GALNT4) mice. The GALNT4-KO mice demonstrated accelerated cardiac hypertrophy, dysfunction, and fibrosis, whereas the opposite phenotype was observed in AAV9-GALNT4 mice. Similarly, GALNT4 overexpression mitigated the degree of phenylephrine-induced cardiomyocyte hypertrophy in vitro whereas GALNT4 knockdown aggravated the hypertrophy. In terms of mechanism, GALNT4 deficiency increased the phosphorylation and activation of ASK1 and its downstream targets (JNK and p38), whereas GALNT4 overexpression inhibited activation of the ASK1 pathway. Furthermore, we demonstrated that GALNT4 can directly bind to ASK1 inhibiting its N-terminally mediated dimerization and the subsequent phosphorylation of ASK1. Finally, an ASK1 inhibitor (iASK1) was able to reverse the effects of GALNT4 in vitro. In summary, GALNT4 may serve as a new regulatory factor and therapeutic target by blocking the activation of the ASK1 signaling cascade.
ERK5 modulates IL-6 secretion and contributes to tumor-induced immune suppression
Authors: Riegel Kristina , Yurugi Hajime , Schlöder Janine , Jonuleit Helmut , Kaulich Manuel , Kirschner Friederike , Arnold-Schild Danielle , Tenzer Stefan , Schild Hansjörg , Rajalingam Krishnaraj
Published: October 2021

Tumors exhibit a variety of strategies to dampen antitumor immune responses. With an aim to identify factors that are secreted from tumor cells, we performed an unbiased mass spectrometry-based secretome analysis in lung cancer cells. Interleukin-6 (IL-6) has been identified as a prominent factor secreted by tumor cells and cancer-associated fibroblasts isolated from cancer patients. Incubation of dendritic cell (DC) cultures with tumor cell supernatants inhibited the production of IL-12p70 in DCs but not the surface expression of other activation markers which is reversed by treatment with IL-6 antibody. Defects in IL-12p70 production in the DCs inhibited the differentiation of Th1 but not Th2 and Th17 cells from naïve CD4+ T cells. We also demonstrate that the classical mitogen-activated protein kinase, ERK5/MAPK7, is required for IL-6 production in tumor cells. Inhibition of ERK5 activity or depletion of ERK5 prevented IL-6 production in tumor cells, which could be exploited for enhancing antitumor immune responses.
CHD8 safeguards early neuroectoderm differentiation in human ESCs and protects from apoptosis during neurogenesis
Authors: Ding Song , Lan Xianchun , Meng Yajing , Yan Chenchao , Li Mao , Li Xiang , Chen Jian , Jiang Wei
Published: October 2021

The chromatin remodeler CHD8, which belongs to the ATP-dependent chromatin remodelers CHD family, is one of the most high-risk mutated genes in autism spectrum disorders. However, the role of CHD8 in neural differentiation and the mechanism of CHD8 in autism remains unclear, despite there are a few studies based on the CHD8 haploinsufficient models. Here, we generate the CHD8 knockout human ESCs by CRISPR/Cas9 technology and characterize the effect of loss-of-function of CHD8 on pluripotency maintenance and lineage determination by utilizing efficient directed differentiation protocols. The results show loss-of-function of CHD8 does not affect human ESC maintenance although having slight effect on proliferation and cell cycle. Interestingly, CHD8 depletion results in defective neuroectoderm differentiation, along with severe cell death in neural progenitor stage. Transcriptome analysis also indicates CHD8 does not alter the expression of pluripotent genes in ESC stage, but in neural progenitor cells depletion of CHD8 induces the abnormal expression of the apoptosis genes and suppresses neuroectoderm-related genes. These results provide the evidence that CHD8 plays an essential role in the pluripotency exit and neuroectoderm differentiation as well as the regulation of apoptosis during neurogenesis.
The emerging roles of neutrophil extracellular traps in wound healing
Authors: Zhu Shuainan , Yu Ying , Ren Yun , Xu Liying , Wang Huilin , Ling Xiaomin , Jin Lin , Hu Yan , Zhang Hao , Miao Changhong , Guo Kefang
Published: October 2021

Delayed wound healing causes problems for many patients both physically and psychologically, contributing to pain, economic burden, loss of function, and even amputation. Although many factors affect the wound healing process, abnormally prolonged or augmented inflammation in the wound site is a common cause of poor wound healing. Excessive neutrophil extracellular trap (NET) formation during this phase may amplify inflammation and hinder wound healing. However, the roles of NETs in wound healing are still unclear. Herein, we briefly introduce NET formation and discuss the possible NET-related mechanisms in wound healing. We conclude with a discussion of current studies, focusing on the roles of NETs in diabetic and normoglycemic wounds and the effectiveness of NET-targeting treatments in wound healing.
CPAP enhances and maintains chronic inflammation in hepatocytes to promote hepatocarcinogenesis
Authors: Chen Ruo-Yu , Yen Chia-Jui , Lin Yih-Jyh , Wang Ju-Ming , Tasi Ting-Fen , Huang Yu-Chuan , Liu Yao-Wen , Tsai Hung-Wen , Lee Ming-Hao , Hung Liang-Yi
Published: October 2021

Chronic and persistent inflammation is a well-known carcinogenesis promoter. Hepatocellular carcinoma (HCC) is one of the most common inflammation-associated cancers; most HCCs arise in the setting of chronic inflammation and hepatic injury. Both NF-κB and STAT3 are important regulators of inflammation. Centrosomal P4.1-associated protein (CPAP), a centrosomal protein that participates primarily in centrosome functions, is overexpressed in HCC and can increase TNF-α-mediated NF-κB activation and IL-6-induced STAT3 activation. A transgenic (Tg) mouse model with hepatocyte-specific CPAP expression was established to investigate the physiological role of CPAP in hepatocarcinogenesis. Obvious inflammatory cell accumulation and fatty change were observed in the livers of CPAP Tg mice. The alanine aminotransferase (ALT) level and the expression levels of inflammatory genes, such as IL-6, IL-1β and TNF-α, were higher in CPAP Tg mice than in wild type (WT) mice. High-dose/short-term treatment with diethylnitrosamine (DEN) increased the ALT level, proinflammatory gene expression levels, and STAT3 and NF-κB activation in CPAP Tg mice; low-dose/long-term DEN treatment induced more severe liver tumor formation in CPAP Tg mice than in WT mice. CPAP can increase the expression of chemokine (C-C motif) ligand 16 (CCL-16), an important chemotactic cytokine, in human hepatocytes. CCL-16 expression is positively correlated with CPAP and TNF-α mRNA expression in the peritumoral part of HCC. In summary, these results suggest that CPAP may promote hepatocarcinogenesis through enhancing the inflammation pathway via increasing the expression of CCL-16.
Effect of tumor-associated macrophages on lncRNA PURPL/miR-363/PDZD2 axis in osteosarcoma cells
Authors: He Fan , Ding Guoming , Jiang Wu , Fan Xiaoliang , Zhu Liulong
Published: October 2021

Tumor-associated macrophages (TAMs) are known to participate in osteosarcoma (OS) progression. As demonstrated in our previous research, miR-363 played a tumor inhibitory effect in OS cells via lowering the PDZ domain containing 2 (PDZD2) expression. The regulatory roles of TAMs on miR-363/PDZD2 and the internal mechanism relating to long noncoding RNA p53 upregulated regulator of P53 levels (lncRNA PURPL) are examined in this study. TAM-like macrophages were formed by inducing CD14+ peripheral blood mononuclear cells (PBMCs). The TAMs migration was detected after MG-63 cells transfected with miR-363 mimics or inhibitors. We then analyzed the regulatory activity of PURPL on miR-363 expression. We also tested the influences of PURPL overexpression/knockdown on MG-63 cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), as well as TAMs migration. Silence in PDZD2 expression was used to confirm the effects of PURPL on MG-63 cells. We successfully induced TAM-like macrophages. MG-63 cells transfecting miR-363 mimics suppressed TAMs migration while transfecting a converse effect was seen in miR-363 inhibitor. TAMs raised PURPL expression in MG-63 cells, which was an upstream regulator of miR-363. Along with TAMs migration, PURPL overexpression promoted MG-63 cell proliferation, migration, invasion, and EMT. An opposite influence was seen due to the PURPL knockdown. The silence of PDZD2 weakened the influences of PURPL overexpression on MG-63 cells and TAMs migration. On modulating the PURPL/miR-363/PDZD2 axis, TAMs-promoted OS development might be achieved.
A small molecule produced by Lactobacillus species blocks Candida albicans filamentation by inhibiting a DYRK1-family kinase
Authors: MacAlpine Jessie , Daniel-Ivad Martin , Liu Zhongle , Yano Junko , Revie Nicole M. , Todd Robert T. , Stogios Peter J. , Sanchez Hiram , O’Meara Teresa R. , Tompkins Thomas A. , Savchenko Alexei , Selmecki Anna , Veri Amanda O. , Andes David R. , Fidel Paul L. , Robbins Nicole , Nodwell Justin , Whitesell Luke , Cowen Leah E.
Published: October 2021

The fungus Candida albicans is an opportunistic pathogen that can exploit imbalances in microbiome composition to invade its human host, causing pathologies ranging from vaginal candidiasis to fungal sepsis. Bacteria of the genus Lactobacillus are colonizers of human mucosa and can produce compounds with bioactivity against C. albicans. Here, we show that some Lactobacillus species produce a small molecule under laboratory conditions that blocks the C. albicans yeast-to-filament transition, an important virulence trait. It remains unexplored whether the compound is produced in the context of the human host. Bioassay-guided fractionation of Lactobacillus-conditioned medium linked this activity to 1-acetyl-β-carboline (1-ABC). We use genetic approaches to show that filamentation inhibition by 1-ABC requires Yak1, a DYRK1-family kinase. Additional biochemical characterization of structurally related 1-ethoxycarbonyl-β-carboline confirms that it inhibits Yak1 and blocks C. albicans biofilm formation. Thus, our findings reveal Lactobacillus-produced 1-ABC can prevent the yeast-to-filament transition in C. albicans through inhibition of Yak1.
A human multi-lineage hepatic organoid model for liver fibrosis
Authors: Guan Yuan , Enejder Annika , Wang Meiyue , Fang Zhuoqing , Cui Lu , Chen Shih-Yu , Wang Jingxiao , Tan Yalun , Wu Manhong , Chen Xinyu , Johansson Patrik K. , Osman Issra , Kunimoto Koshi , Russo Pierre , Heilshorn Sarah C. , Peltz Gary
Published: October 2021

To investigate the pathogenesis of a congenital form of hepatic fibrosis, human hepatic organoids were engineered to express the most common causative mutation for Autosomal Recessive Polycystic Kidney Disease (ARPKD). Here we show that these hepatic organoids develop the key features of ARPKD liver pathology (abnormal bile ducts and fibrosis) in only 21 days. The ARPKD mutation increases collagen abundance and thick collagen fiber production in hepatic organoids, which mirrors ARPKD liver tissue pathology. Transcriptomic and other analyses indicate that the ARPKD mutation generates cholangiocytes with increased TGFβ pathway activation, which are actively involved stimulating myofibroblasts to form collagen fibers. There is also an expansion of collagen-producing myofibroblasts with markedly increased PDGFRB protein expression and an activated STAT3 signaling pathway. Moreover, the transcriptome of ARPKD organoid myofibroblasts resemble those present in commonly occurring forms of liver fibrosis. PDGFRB pathway involvement was confirmed by the anti-fibrotic effect observed when ARPKD organoids were treated with PDGFRB inhibitors. Besides providing insight into the pathogenesis of congenital (and possibly acquired) forms of liver fibrosis, ARPKD organoids could also be used to test the anti-fibrotic efficacy of potential anti-fibrotic therapies.
Targeting miR-126 in inv(16) acute myeloid leukemia inhibits leukemia development and leukemia stem cell maintenance
Authors: Zhang Lianjun , Nguyen Le Xuan Truong , Chen Ying-Chieh , Wu Dijiong , Cook Guerry J. , Hoang Dinh Hoa , Brewer Casey J. , He Xin , Dong Haojie , Li Shu , Li Man , Zhao Dandan , Qi Jing , Hua Wei-Kai , Cai Qi , Carnahan Emily , Chen Wei , Wu Xiwei , Swiderski Piotr , Rockne Russell C. , Kortylewski Marcin , Li Ling , Zhang Bin , Marcucci Guido , Kuo Ya-Huei
Published: October 2021

Acute myeloid leukemia (AML) harboring inv(16)(p13q22) expresses high levels of miR-126. Here we show that theCBFB-MYH11 (CM)fusion gene upregulates miR-126 expression through aberrant miR-126 transcription and perturbed miR-126 biogenesis via the HDAC8/RAN-XPO5-RCC1 axis. Aberrant miR-126 upregulation promotes survival of leukemia-initiating progenitors and is critical for initiating and maintaining CM-driven AML. We show that miR-126 enhances MYC activity through the SPRED1/PLK2-ERK-MYC axis. Notably, genetic deletion of miR-126 significantly reduces AML rate and extends survival in CM knock-in mice. Therapeutic depletion of miR-126 with an anti-miR-126 (miRisten) inhibits AML cell survival, reduces leukemia burden and leukemia stem cell (LSC) activity in inv(16) AML murine and xenograft models. The combination of miRisten with chemotherapy further enhances the anti-leukemia and anti-LSC activity. Overall, this study provides molecular insights for the mechanism and impact of miR-126 dysregulation in leukemogenesis and highlights the potential of miR-126 depletion as a therapeutic approach for inv(16) AML.
Optimization of training and measurement protocol for eNose analysis of urine headspace aimed at prostate cancer diagnosis
Authors: Capelli Laura , Bax Carmen , Grizzi Fabio , Taverna Gianluigi
Published: October 2021

More than one million new cases of prostate cancer (PCa) were reported worldwide in 2020, and a significant increase of PCa incidence up to 2040 is estimated. Despite potential treatability in early stages, PCa diagnosis is challenging because of late symptoms’ onset and limits of current screening procedures. It has been now accepted that cell transformation leads to release of volatile organic compounds in biologic fluids, including urine. Thus, several studies proposed the possibility to develop new diagnostic tools based on urine analysis. Among these, electronic noses (eNoses) represent one of the most promising devices, because of their potential to provide a non-invasive diagnosis. Here we describe the approach aimed at defining the experimental protocol for eNose application for PCa diagnosis. Our research investigates effects of sample preparation and analysis on eNose responses and repeatability. The dependence of eNose diagnostic performance on urine portion analysed, techniques involved for extracting urine volatiles and conditioning temperature were analysed. 192 subjects (132 PCa patients and 60 controls) were involved. The developed experimental protocol has resulted in accuracy, sensitivity and specificity of 83% (CI95% 77–89), 82% (CI95% 73–88) and 87% (CI95% 75–94), respectively. Our findings define eNoses as valuable diagnostic tool allowing rapid and non-invasive PCa diagnosis.
Mapping the NFT revolution: market trends, trade networks, and visual features
Authors: Nadini Matthieu , Alessandretti Laura , Di Giacinto Flavio , Martino Mauro , Aiello Luca Maria , Baronchelli Andrea
Published: October 2021

Non Fungible Tokens (NFTs) are digital assets that represent objects like art, collectible, and in-game items. They are traded online, often with cryptocurrency, and are generally encoded within smart contracts on a blockchain. Public attention towards NFTs has exploded in 2021, when their market has experienced record sales, but little is known about the overall structure and evolution of its market. Here, we analyse data concerning 6.1 million trades of 4.7 million NFTs between June 23, 2017 and April 27, 2021, obtained primarily from Ethereum and WAX blockchains. First, we characterize statistical properties of the market. Second, we build the network of interactions, show that traders typically specialize on NFTs associated with similar objects and form tight clusters with other traders that exchange the same kind of objects. Third, we cluster objects associated to NFTs according to their visual features and show that collections contain visually homogeneous objects. Finally, we investigate the predictability of NFT sales using simple machine learning algorithms and find that sale history and, secondarily, visual features are good predictors for price. We anticipate that these findings will stimulate further research on NFT production, adoption, and trading in different contexts.
Biosorption of cationic Hg2+ and Remazol brilliant blue anionic dye from binary solution using Gelidium corneum biomass
Authors: El-Ahmady Ali El-Naggar Noura , Hamouda Ragaa A. , El-Khateeb Ayman Y. , Rabei Nashwa H.
Published: October 2021

Remazol brilliant blue (RBB) is an anthraquinone anionic dye that has several commercial uses, especially in the textile industries and is well-known for its detrimental impacts on marine life and the surrounding ecosystem. Mercury (Hg2+) is also one of the most severe hazardous environmental contaminants due to its bioaccumulation through the food chain and high toxicity to the human embryo and fetus. The biosorption potential of Gelidium corneum biomass for bioremoval of Hg2+ and RBB dye simultaneously from binary mixture was assessed. The effects of initial pH, contact time, Hg2+, RBB, and biomass concentrations on the biosorption process were investigated in 50 batch experiments using a Face-centered central composite design. The maximum removal percentage of Hg2+ (98.25%) was achieved in the run no. 14, under optimum experimental conditions: 200 mg/L Hg2+, 75 mg/L RBB, pH 5. At 30 °C, 4 g/L algal biomass was used, with a contact time of 180 min. Whereas, the maximum removal percentage of RBB (89.18%) was obtained in the run no. 49 using 200 mg/L Hg2+, 100 mg/L RBB, pH 5, 4 g/L algal biomass and 180 min of contact time. FTIR analysis of Gelidium corneum biomass surface demonstrated the presence of many functional groups that are important binding sites responsible for Hg2+ and RBB biosorption. SEM analysis showed apparent morphological alterations including surface shrinkage and the appearance of new shiny adsorbate ion particles on the Gelidium corneum biomass surface after the biosorption process. The EDX study reveals an additional optical absorption peak for Hg2+, confirming the role of Gelidium corneum biomass in Hg2+ biosorption. In conclusion, Gelidium corneum biomass has been shown to be an eco-friendly, sustainable, promising, cost-effective and biodegradable biosorbent to simultaneously biosorb Hg2+ and RBB dye from aquatic ecosystems.
Whole genome sequencing and protein structure analyses of target genes for the detection of Salmonella
Authors: Hu Lijun , Cao Guojie , Brown Eric W. , Allard Marc W. , Ma Li M. , Zhang Guodong
Published: October 2021

Rapid and sensitive detection of Salmonella is a critical step in routine food quality control, outbreak investigation, and food recalls. Although various genes have been the targets in the design of rapid molecular detection methods for Salmonella, there is limited information on the diversity of these target genes at the level of DNA sequence and the encoded protein structures. In this study, we investigated the diversity of ten target genes (invA, fimA, phoP, spvC, and agfA; ttrRSBCA operon including 5 genes) commonly used in the detection and identification of Salmonella. To this end, we performed whole genome sequencing of 143 isolates of Salmonella serotypes (Enteritidis, Typhimurium, and Heidelberg) obtained from poultry (eggs and chicken). Phylogenetic analysis showed that Salmonella ser. Typhimurium was more diverse than either Enteritidis or Heidelberg. Forty-five non-synonymous mutations were identified in the target genes from the 143 isolates, with the two most common mutations as T ↔ C (15 times) and A ↔ G (13 times). The gene spvC was primarily present in Salmonella ser. Enteritidis isolates and absent from Heidelberg isolates, whereas ttrR was more conserved (0 non-synonymous mutations) than ttrS, ttrB, ttrC, and ttrA (7, 2, 2, and 7 non-synonymous mutations, respectively). Notably, we found one non-synonymous mutation (fimA-Mut.6) across all Salmonella ser. Enteritidis and Salmonella ser. Heidelberg, C → T (496 nt postion), resulting in the change at AA 166 position, Glutamine (Q) → Stop condon (TAG), suggesting that the fimA gene has questionable sites as a target for detection. Using Phyre2 and SWISS-MODEL software, we predicted the structures of the proteins encoded by some of the target genes, illustrating the positions of these non-synonymous mutations that mainly located on the α-helix and β-sheet which are key elements for maintaining the conformation of proteins. These results will facilitate the development of sensitive molecular detection methods for Salmonella.
Wnt6 plays a complex role in maintaining human limbal stem/progenitor cells
Authors: Bonnet Clémence , Oh Denise , Mei Hua , Robertson Sarah , Chang Derek , Bourges Jean-Louis , Behar-Cohen Francine , Zheng Jie J. , Deng Sophie X.
Published: October 2021

The corneal epithelium is consistently regenerated by limbal stem/progenitor cells (LSCs), a very small population of adult stem cells residing in the limbus. Several Wnt ligands, including Wnt6, are preferentially expressed in the limbus. To investigate the role of Wnt6 in regulating proliferation and maintenance of human LSCs in an in vitro LSC expansion setting, we generated NIH-3T3 feeder cells to overexpress different levels of Wnt6. Characterization of LSCs cultured on Wnt6 expressing 3T3 cells showed that high level of Wnt6 increased proliferation of LSCs. Medium and high levels of Wnt6 also increased the percentage of small cells (diameter ≤ 12 µm), a feature of the stem cell population. Additionally, the percentage of cells expressing the differentiation marker K12 was significantly reduced in the presence of medium and high Wnt6 levels. Although Wnt6 is mostly known as a canonical Wnt ligand, our data showed that canonical and non-canonical Wnt signaling pathways were activated in the Wnt6-supplemented LSC cultures, a finding suggesting that interrelationships between both pathways are required for LSC regulation.
Investigation of the out-of-plane load-bearing capacity of T1100/5405 composite T-stiffened panels
Authors: Huang Heyuan , Zhang Xuanjia , Dong Zhicheng , Wang Dong
Published: October 2021

With the continuous improvement of the mechanical properties of composite materials, the adhesive interface performance of composite T-stiffened panels has become a critical factor in determining the overall structural strength. However, little work has been reported on the mechanical properties of adhesive interfaces in composite T-stiffened panels under lateral bending and shear loading. Especially, there is no clear explanation on the damage evolution law of structural properties for the interface with defects, which greatly influenced the use of T-stiffened composite structures. In this paper, the mechanical properties of T1100/5405 composite T-stiffened laminates under lateral bending and shear loading are experimentally and numerically investigated. The load-bearing capacities for the panels with intact and defected adhesive interfaces are compared, the damage evolution law of typical T-stiffened structures is further explored. Based on the continuum damage model (CDM) and the cohesive zone model (CZM), the constitutive models of the adhesive layer and the composite material are established respectively. Good agreements between experimental and numerical profiles illustrate that damages mainly occur on the loading side and the corner of the L-type ribs under lateral bending conditions, while damages extend from both sides of the interface layer to the center under shear loading. When a prefabricated defect exists, damages extend from the defect location along the loading direction. At the same time, the analysis shows that the lay-up of the surface layer, the chamfer radius, and the width of T-type ribs have a great influence on the structural load-bearing capacity, but less on the damage evolution form.
Field evidence for microplastic interactions in marine benthic invertebrates
Authors: Vecchi Stefania , Bianchi Jessica , Scalici Massimiliano , Fabroni Fabrizio , Tomassetti Paolo
Published: October 2021

Microplastics represent an important issue of concern for marine ecosystems worldwide, and closed seas, such as the Mediterranean, are among the most affected by this increasing threat. These pollutants accumulate in large quantities in benthic environments causing detrimental effects on diverse biocenoses. The main focus of this study is on the ‘polychaetes-microplastics’ interactions, particularly on two species of benthic polychaetes with different ecology and feeding strategies: the sessile and filter feederSabella spallanzanii(Gmelin, 1791) and the vagile carnivorousHermodice carunculata(Pallas, 1766). Since not standardized protocols are proposed in literature to date, we compared efficiencies of diverse common procedures suitable for digesting organic matter of polychaetes. After the definition of an efficient digestion protocol for microplastics extraction for both polychaetes, our results showed high microplastics ingestion in both species. Microplastics were found in 42% of individualsof S. spallanzanii, with a mean of 1 (± 1.62) microplastics per individual, in almost all individuals ofH. carunculata(93%), with a mean of 3.35 (± 2.60). These significant differences emerged betweenS. spallanzaniiandH. carunculata, is probably due to the diverse feeding strategies. The susceptibility to this pollutant makes these species good bioindicators of the impact of microplastics on biota.