bluuebunny/crossref_metadata_2025 huggingface dataset:
Lysyl Oxidase‐Like 4 Fosters an Immunosuppressive Microenvironment During Hepatocarcinogenesis
Authors: Tan Hor‐Yue , Wang Ning , Zhang Cheng , Chan Yau‐Tuen , Yuen Man‐Fung , Feng Yibin
Published: October 2020

Background and Aims

Lysyl oxidase‐like 4 (LOXL4) is an amine oxidase that is primarily involved in extracellular matrix remodeling and is highly expressed in HCC tissues, but its functional role in mediating liver carcinogenesis is poorly understood. Therefore, we aimed to investigate the role of LOXL4 in hepatocarcinogenesis.

Approach and Results

Here, we demonstrate that hepatic LOXL4 expression was increased during the liver carcinogenesis in mice concomitantly fed a choline‐deficient, l‐amino acid–defined diet. LOXL4 was secreted by the neoplastic cells and primarily localized within hepatic macrophages through exosome internalization. Supplementation of LOXL4 had minimal effect on neoplastic cells. In vitro exposure of macrophages to LOXL4 invoked an immunosuppressive phenotype and activated programmed death ligand 1 (PD‐L1) expression, which further suppressed the function of CD8+ T cells. Injection of LOXL4 promoted macrophages infiltration into the liver and accelerated tumor growth, which was further abolished by adoptive T‐cell transfer or PD‐L1 neutralization. Label‐free proteomics analysis revealed that the immunosuppressive function of LOXL4 on macrophages primarily relied on interferon (IFN)‐mediated signal transducer and activator of transcription–dependent PD‐L1 activation. Hydrogen peroxide scavenger or copper chelation on macrophages abolished the IFN‐mediated PD‐L1 presentation by LOXL4. In human HCC tissue, expression of LOXL4 in CD68+ cells was positively correlated with PD‐L1 level. High expression of LOXL4 in CD68+ cells and low expression of CD8A in tumor tissue cooperatively predict poor survival of patients with HCC.

Conclusions

LOXL4 facilitates immune evasion by tumor cells and leads to hepatocarcinogenesis. Our study unveils the role of LOXL4 in fostering an immunosuppressive microenvironment during hepatocarcinogenesis.
Food community: Understanding community needs for a food security website to support rural and remote Western Australians
Authors: Rewa Johanna , Devine Amanda , Godrich Stephanie
Published: October 2020

Objective

The South West Food Community (SWFC) project (2018) was implemented to identify initiatives working to enhance healthy food availability, access and use in the South West region of Western Australia (SWWA); and enhance how they functioned as a system. The SWFC project participants included government and community members. This study aimed to understand how a tailored food security website could be developed as a support mechanism to increase understanding of food security, connect participants and enhance the effectiveness of SWFC initiatives.

Methods

Initiative leaders from the SWFC project (n = 46) were invited to participate in semi‐structured telephone interviews which sought to understand needs for a food security website. Fifteen stakeholders completed the interviews (32% response rate). Data relating to desirable and undesirable website components were analysed thematically using QSR NVivo 12.

Results

Participants requested the website to include concise content, food security resources, inviting/useful images and information about initiatives. Undesirable features included academic literature, difficult‐to‐use functions, discussion boards and hard‐to‐view images.

Conclusion

A tailored, co‐designed website that is monitored, user‐friendly and functional were key stakeholder requirements.

Implications for Public Health

A tailored, co‐designed food security website that promotes partnership development, builds networks, increases understanding and communication about food security and implementation strategies is needed.
Applying the Mandala of Health in the Anthropocene
Authors: Langmaid Georgia , Patrick Rebecca , Kingsley Jonathan , Lawson Justin
Published: October 2020

Issue addressed

The Anthropocene is a new era in which human activity has been the dominant influence on climate and the environment. The negative impact humans have on the earth's systems pose significant threats to human health. Health promotion is a discipline well placed to respond to planetary health challenges of the Anthropocene. The overarching aim of this paper is to describe the elements of 21st century socio‐ecological health and apply them in a revised socio‐ecological framework for health promotion.

Methods

A qualitative description study design was employed to explore the significance of ecological and cultural determinants of health and review models in contemporary health promotion to inform the development of a revised Mandala of Health. Purposeful sampling was used to recruit ten experts from across Australia including academics and practitioners working at the nexus of health promotion, environmental management and sustainability. Data were analysed thematically, using deductive and inductive methods.

Results

A revised Mandala of Health could address existing gaps in health promotion theory and practice. Ecological and cultural determinants of health were considered essential components of health promotion that is often lacking in socio‐ecological frameworks. Indigenous Knowledge Systems were considered immensely important when addressing ecological and cultural determinants of health.

Conclusions

A revised Mandala of Health could encourage development of contemporary health models, assisting health promotion to evolve with the health and environmental issues of the Anthropocene. This study highlights the need for more theoretical development and empirical research regarding ecological and cultural determinants of health in a health promotion context.

So what?

In the context of the Anthropocene, this study highlights the potential gaps in health promotion theory and practice in terms of the natural environment and health and emphasises the need of a paradigm shift to embed ecological and cultural determinants with other determinants of health.
Antibiotic treatment of amniotic fluid “sludge” in patients during the second or third trimester with uterine contraction
Authors: Jin Wan Hu , Ha Kim Yoon , Kim Jong Woon , Kim Tae Young , Kim Ami , Yang Yoonmi
Published: October 2020

Objective

To assess the effectiveness of antibiotic treatment in patients with amniotic fluid (AF) “sludge” during the second or third trimester with uterine contractions and intact membranes.

Methods

A retrospective cohort study was conducted of women at 15–32 weeks of pregnancy with uterine contractions and intact membranes. Women with AF “sludge” were treated with an antibiotic regimen of ceftriaxone, clarithromycin, and metronidazole. Based on changes in AF “sludge,” patients were divided into group A (disappearance of “sludge”) and group B (persistent “sludge”).

Results

Women in group A (n=30) delivered later than those in group B (n=28). Group A showed a smaller initial size of “sludge” than group B (all P<0.05). Women in group A had a lower rate of preterm birth within 7 days, and before 28, 32, and 34 weeks of pregnancy, and composite neonatal morbidity and perinatal death than group B (all P<0.05).

Conclusion

The administration of antibiotics may eradicate AF “sludge” in women in the second or third trimester with uterine contractions and intact membranes, which are associated with the initial size of “sludge.” Patients with disappearing “sludge” had more favorable pregnancy and neonatal outcomes than those with persistent “sludge.”
Development and clinical application of a rapid SARS‐CoV‐2 antibody test strip: A multi‐center assessment across China
Authors: Liao Mengting , Yan Jiawei , Wang Xinfeng , Qian Huimin , Wang Chao , Xu Dan , Wang Bin , Yang Bo , Liu Shaohui , Zhou Mao , Gao Qian , Zhou Qian , Luo Jiquan , Li Zongxiang , Liu Wenen
Published: October 2020

Background

The ongoing coronavirus disease 19 (COVID‐19) is posing a threat to the public health globally. Serological test for SARS‐CoV‐2 antibody can improve early diagnosis of COVID‐19 and serves as a valuable supplement to RNA detection.

Method

A SARS‐CoV‐2 IgG/IgM combined antibody test strip based on colloidal gold immunochromatography assay was developed, with both spike protein and nucleocapsid protein of SARS‐CoV‐2 antigen used for antibody detection. From 3 medical institutions across China, serum or plasma of 170 patients with confirmed COVID‐19 diagnosis and 300 normal controls were collected and tested with the strip. Sensitivity, specificity, kappa coefficient, receiver operating characteristic (ROC) curve, and area under the curve (AUC) were analyzed. Positive rates in different medical centers, age group, gender, and different disease course were compared.

Results

158 out 170 samples from confirmed COVID‐19 patients had positive results from the test, and 296 out of 300 samples from normal controls had negative results. The kit was 92.9% sensitive and 98.7% specific. The positive rate was 77.3% during the first week after disease onset, but reached 100% since day 9. AUC and kappa coefficient were 0.958 and 0.926, respectively, which showed the consistency of the test results with the standard diagnosis. Age or gender caused little variations in the kit sensitivity.

Conclusion

The rapid, easy‐to‐use SARS‐CoV‐2 IgG/IgM combined antibody test kit has a superior performance, which can help with accurate diagnosis and thus timely treatment and isolation of COVID‐19 patients, that contributes to the better control of the global pandemic.
Thromboelastography (TEG) in normal pregnancy and its diagnostic efficacy in patients with gestational hypertension, gestational diabetes mellitus, or preeclampsia
Authors: Xie Xin , Wang Meng , Lu Yifan , Zeng Jiazi , Wang Jing , Zhang Chunhong , Zhu Hongyuan , Song Yujie , Han Lican , Liu Ying , Zhang Jingnan , Li Lei , Chen Lu , Zhai Yanhong , Cao Zheng
Published: October 2020

Background

Thromboelastography (TEG) provides global assessment of hemostatic function and has been recommended to monitor potential coagulopathies during pregnancy in which hypercoagulable state is favored. In present study, we established the reference intervals (RIs) of the TEG parameters (R, K, MA, and α‐angle) with Chinese pregnant women of third trimester. In addition, we examined the diagnostic efficacies of the TEG parameters in the patients diagnosed of gestational hypertension (GH), gestational diabetes mellitus (GDM), or preeclampsia (PE).

Methods

With specified including and excluding criteria, non‐pregnant controls, healthy pregnant women, and pregnant women with GH, GDM, or PE had their venous blood drawn at Beijing Obstetrics and Gynecology Hospital, followed by TEG tests performed in the clinical laboratory.

Results

The RIs determined with the healthy pregnant women (in third trimester) for R, K, MA, and α‐angle were 4.0‐7.7, 1.2‐3.2, 51.9‐70.1, and 41.4‐74.4, respectively. When compared with the healthy pregnancy group, the K value was significantly decreased in GH patients but increased in PE patients; MA was significantly lower in the PE group. In the receiver operating characteristic curve (ROC) analyses, K value was able to efficiently distinguish normal pregnancy from the GH patients, with an AUC of 0.86 which is far better than those of R (AUC = 0.57) and MA (AUC = 0.56). For the PE patients, the AUC of MA (0.69) was significantly greater than that of R (0.50).

Conclusions

Thromboelastography may provide more accurate experimental basis for monitoring coagulation functions especially in pregnant women with complications of GH and PE.
Quantitative analyses of high‐angular resolution diffusion imaging (HARDI)‐derived long association fibers in children with sensorineural hearing loss
Authors: Shiohama Tadashi , Chew Brianna , Levman Jacob , Takahashi Emi
Published: October 2020

Sensorineural hearing loss (SNHL) is the most common developmental sensory disorder due to a loss of function within the inner ear or its connections to the brain. While successful intervention for auditory deprivation with hearing amplification and cochlear implants during a sensitive early developmental period can improve spoken‐language outcomes, SNHL patients can suffer several cognitive dysfunctions including executive function deficits, visual cognitive impairment, and abnormal visual dominance in speaking perception even after successful intervention. To evaluate whether long association fibers are involved in the pathogenesis of impairment on the extra‐auditory cognitive process in SNHL participants, we quantitatively analyzed high‐angular resolution diffusion imaging (HARDI) tractography‐derived fibers in participants with SNHL. After excluding cases with congenital disorders, perinatal brain damage, or premature birth, we enrolled 17 participants with SNHL aged under 10 years old. Callosal pathways (CP) and six types of cortico‐cortical association fibers (arcuate fasciculus [AF], inferior longitudinal fasciculus [ILF], inferior fronto‐occipital fasciculus [IFOF], uncinate fasciculus [UF], cingulum fasciculus [CF], and fornix [Fx]) in both hemispheres were identified and visualized. The ILF and IFOF were partly undetected in three profound SNHL participants. Compared to age‐ and gender‐matched neurotypical controls (NC), decreased volumes, increased lengths, and high apparent diffusion coefficient (ADC) values without difference in fractional anisotropy (FA) values were identified in multiple types of fibers in the SNHL group. The impairment of long association fibers in SNHL may partly be related to the association of cognitive dysfunction with SNHL.
Not deconstructing serial homology, but instead, the a priori assumption that it generally involves ancestral anatomical similarity: An answer to Kuznetsov's paper
Authors: Diogo Rui
Published: October 2020

I am very thankful to Kuznetsov for his comments on our recent paper about serial structures published in this journal. I hope this is just the beginning of a much wider, and holistic, discussion on the evolution of serial homologous structures, and of so‐called “serial structures” in general, whether they are truly serial homologs or the secondary result of homoplasy. Strangely, Kuznetsov seems to have missed the main point of our paper, what is particularly puzzling as this point is clearly made in the very title of our paper. For instance, he states that “Siomava et al. claim that the serial homologues are false because they are ancestrally anisomeric (dissimilar)' and that” Siomava et al., (Siomava et al., Journal of Morphology, 2020, 281, 1110–1132) expected that if serial homology was true, then the serial homologs would be identical at the start and then only diverge. “ However, our paper clearly did not state this. Instead, we stated that (a) serial homology is a real phenomenon, and (b) ancestral dissimilarity is actually likely the norm, and not the exception, within serial homology. In particular, our paper showed that, as clearly stated in its title and abstract, within the evolution of serial homologues these structures “many times display trends toward less similarity while in many others display trends toward more similarity, that is, one cannot say that there is a clear, overall trend to anisomerism.” Serial homology is therefore a genuine and much widespread phenomenon within the evolution of life in this planet. It is clearly one of the most important issues—and paradoxically one of the less understood, precisely because of the a priori acceptance of long‐standing assumptions that have never been empirically tested, some of them repeated in Kuznetsov's paper—within macroevolution and comparative anatomy.
Multishot Diffusion‐Weighted MRI of the Breast With Multiplexed Sensitivity Encoding (MUSE) and Shot Locally Low‐Rank (Shot‐LLR) Reconstructions
Authors: Hu Yuxin , Ikeda Debra M. , Pittman Sarah M. , Samarawickrama Dilan , Guidon Arnaud , Rosenberg Jarrett , Chen Shu‐tian , Okamoto Satoko , Daniel Bruce L. , Hargreaves Brian A. , Moran Catherine J.
Published: October 2020

Background

Diffusion‐weighted imaging (DWI) has shown promise to screen for breast cancer without a contrast injection, but image distortion and low spatial resolution limit standard single‐shot DWI. Multishot DWI methods address these limitations but introduce shot‐to‐shot phase variations requiring correction during reconstruction.

Purpose

To investigate the performance of two multishot DWI reconstruction methods, multiplexed sensitivity encoding (MUSE) and shot locally low‐rank (shot‐LLR), compared to single‐shot DWI in the breast.

Study Type

Prospective.

Population

A total of 45 women who consented to have multishot DWI added to a clinically indicated breast MRI.

Field Strength/Sequences

Single‐shot DWI reconstructed by parallel imaging, multishot DWI with four or eight shots reconstructed by MUSE and shot‐LLR, 3D T2‐weighted imaging, and contrast‐enhanced MRI at 3T.

Assessment

Three blinded observers scored images for 1) general image quality (perceived signal‐to‐noise ratio [SNR], ghosting, distortion), 2) lesion features (discernment and morphology), and 3) perceived resolution. Apparent diffusion coefficient (ADC) of the lesion was also measured and compared between methods.

Statistical Tests

Image quality features and perceived resolution were assessed with a mixed‐effects logistic regression. Agreement among observers was estimated with a Krippendorf's alpha using linear weighting. Lesion feature ratings were visualized using histograms, and correlation coefficients of lesion ADC between different methods were calculated.

Results

MUSE and shot‐LLR images were rated to have significantly better perceived resolution (P < 0.001), higher SNR (P < 0.005), and a lower level of distortion (P < 0.05) with respect to single‐shot DWI. Shot‐LLR showed reduced ghosting artifacts with respect to both MUSE (P < 0.001) and single‐shot DWI (P < 0.001). Eight‐shot DWI had improved perceived SNR and perceived resolution with respect to four‐shot DWI (P < 0.005).

Data Conclusion

Multishot DWI enables increased resolution and improved image quality with respect to single‐shot DWI in the breast. Shot‐LLR reconstructs multishot DWI with minimal ghosting artifacts. The improvement of multishot DWI in image quality increases with an increased number of shots.

Level of Evidence

2

Technical Efficacy Stage

2
The Japanese Catheter Ablation Registry (J‐AB): A prospective nationwide multicenter registry in Japan. Annual report in 2018
Authors: Kusano Kengo , Yamane Teiichi , Inoue Koichi , Takegami Misa , Nakao Yoko M. , Miyamoto Yoshihiro , Shoda Morio , Nogami Akihiko ,   J‐AB registry investigators
Published: October 2020

Background

To analyze the type of ablation procedure, acute outcomes, and complications related to catheter ablation in Japan during the year of 2018.

Method

The Japanese Catheter Ablation (J‐AB) registry is a voluntary, nationwide, multicenter, prospective, observational registry, performed by the Japanese Heart Rhythm Society (JHRS) in collaboration with the National Cerebral and Cardiovascular Center using a Research Electronic Data Capture system. The procedural outcome and complications during hospitalizations were collected.

Result

A total of 55 525 procedures (mean age of 64.5 years and 66.5% male) from 369 hospitals were collected. The total number of target arrhythmias was 61 610 including atrial fibrillation (AF, 65.6%), atrial flutter (AFL) or atrial tachycardia (16.7%), atrioventricular nodal reentrant tachycardia (7.4%), atrioventricular reentrant tachycardia (3.5%), premature ventricular contractions (4.1%), and ventricular tachycardia (VT, 2.0%). Over a 90% acute success rate was observed among all arrhythmias except for VT due to structural heart disease, and notably, an over 99% success rate was achieved for pulmonary vein isolation of AF and inferior vena cava‐tricuspid valve isthmus block for isthmus‐dependent AFL. Acute complications during hospitalization were observed in 1558 patients (2.8%), including major bleeding (Bleeding Academic Research Consortium: BARC criteria ≥2) in 1.1%, cerebral or systemic embolisms in 0.2%, and death in 0.1%. Acute complications were more often observed with AF ablation (P < .001), especially the first AF ablation session and with structural heart disease (P < .001).

Conclusion

The J‐AB registry provided real‐world data regarding the acute outcomes and complications of ablation for the various types of arrhythmias in Japan.
A comprehensive analysis of meteorological drought stress over the Yellow River basin (China) for the next 40 years
Authors: Ma Mingwei , Yuan Fei , Cui Huijuan , Ren Liliang , Liu Yi
Published: October 2020

The complexity of climate system dynamics calls for more elaborate drought evaluation and trend projection under different future climate scenarios. In this study, the meteorological drought stress over the Yellow River basin (YRB) of China for the next forty years (2021–2060) is comprehensively evaluated based on meteorological simulations of eight climate models from the Coupled Model Intercomparison Project Phase 5 (CMIP5) with three representative concentration pathway scenarios (RCP2.6, RCP4.5 and RCP8.5). The standardized precipitation evapotranspiration index (SPEI) is used as a metric of drought magnitude at multiple temporal scales, while the multi‐threshold run analysis is conducted for the definition of drought events and derivation of drought characteristics (e.g., frequency, duration and severity). The Mann–Kendall test is adopted as a universal tool to analyse the trends in climate variables (precipitation and temperature), multi‐temporal SPEI drought indices and drought characteristics (duration and severity). Our preliminary conclusions include that partially increasing precipitation and generally rising temperature are likely to be seen in the YRB from 2021 to 2060. More importantly, a warmer YRB may undergo either a nearly regular atmospheric regime (e.g., comparable to the baseline period of 1961–2000) with RCP2.6 scenario or significantly drying processes with RCP4.5 and RCP8.5 scenarios. Meanwhile, the enhanced spatiotemporal variability/heterogeneity of meteorological forcing (e.g., precipitation and temperature) and drought characteristics (e.g., magnitude, frequency, duration and severity) would also increase future uncertainty of meteorological drought stress over the YRB, such as the encounter of drought with long duration and/or high severity and relevant increasing trends. Understanding the spatiotemporal influences of specific climate and emission scenarios on projected drought vulnerability might help improving our knowledge of climate‐human interactions and selecting rational development strategy (like the low emission scenario of RCP2.6 or so) for regional adaptation to future climate change.
Mire microclimate: Groundwater buffers temperature in waterlogged versus dry soils
Authors: Fernández‐Pascual Eduardo , Correia‐Álvarez Eva
Published: October 2020

Ecosystems adapt differently to global warming through microclimatic factors. Mires are sensitive wetland habitats that strongly rely on local soil properties, making them a good model to understand how local climatic parameters counteract the effects of climate change. We quantified the temperature buffering effect in waterlogged mire soils as compared with adjacent dry soils. We buried dataloggers at 5 cm depth in waterlogged and dry points in eight mires of the Cantabrian Mountains (Spain, southwestern Europe) and recorded soil temperatures for ca. 5 years. We also compared our local measures with air temperatures predicted by the CHELSA model. Waterlogged soils had less diurnal thermal amplitude (−2.3°C), less annual thermal amplitude (−5.1°C), cooler summer maxima (−4.3°C) and warmer winter minima (+0.8°C). CHELSA air temperatures only correlated significantly (p < .05) with winter minimum soil temperatures (Pearson's r > .83), and CHELSA predictions were less accurate (higher root‐mean‐square error [RMSE]) for waterlogged soils, except for the summer maxima. We conclude that mire soils show a thermal buffer effect that insulates them from the surrounding landscape. This effect is stronger at the warm end of the climatic spectrum, that is, during summer and at lower elevations. These results highlight the potential refugial character of mires under global warming, and the need to integrate microclimate measurements into climate change models.
Polymeric Microspheres Containing Human Vocal Fold Fibroblasts for Vocal Fold Regeneration
Authors: Reyes Valenzuela Alicia , Bao Guangyu , Vikstrom Abigail , Kost Karen M. , Prakash Satya , Mongeau Luc
Published: October 2020

Objective

Most acellular injectable biomaterials for vocal fold (VF) wound treatment have limited regenerative potential due to their fast enzymatic degradation and limited recruitment of native cells postinjection. The injection of cells as therapeutic treatment often results in apoptosis due to stresses within the needle and the immune response of the host. Degradable microspheres may improve treatment effectiveness by increasing cell residence time, shielding cells during injection, and offering early protection against the immune system response. The objective of the present study was to investigate the potential of human VF fibroblasts encapsulated in polymeric microspheres as an injectable therapeutic treatment in vitro.

Methods

Alginate, alginate‐poly‐L‐lysine, and alginate‐chitosan microspheres were fabricated using electrospraying and characterized in terms of biocompatibility, swelling, and mechanical properties as well as cytokine production.

Results

Alginate microspheres were found to have the most desirable properties for VF regeneration. They were resistant to mechanical challenges. They were found to have a stiffness similar to that reported for native VF‐lamina propria. They were found to be biocompatible and increased the proliferation of fibroblasts. Human VF fibroblasts encapsulated in alginate microspheres induced the production of interleukin (IL)‐8 and IL‐4 at 24 hours.

Conclusion

The alginate microspheres fabricated in this study were found to offer potential advantages, as cell delivery tool. This study highlights the importance of combining biomaterials and cells to expedite the wound‐healing process through cytokine production. Future work is aimed to further analysis of the wound‐healing properties the microspheres.

Level of Evidence

NA Laryngoscope, 131:1828–1834, 2021
Assessing spatiotemporal characteristics of native and invasive species with multi‐temporal remote sensing images in the Yellow River Delta, China
Authors: Gong Zhaoning , Zhang Cheng , Zhang Lei , Bai Junhong , Zhou Demin
Published: October 2020

As the main invasive plant species in the Yellow River Delta, Spartina alterniflora (S. alterniflora) has been a great threat to local ecosystems, but there are few studies on the growth scale, habitat structural changes, and expansion pattern of S. alterniflora. In this study, the native and invasive species in the Yellow River Delta were examined for their spatiotemporal characteristics and succession patterns. First, multi‐temporal SENTINEL‐2 and LANDSAT‐8 images from 2018 were selected. A random forest algorithm was used to verify the image spectral band's significance and separability to determine the native and invasive species. Then, the spatiotemporal variation of habitat structure of the species was discussed in depth from the perspective of landscape ecology. Finally, the expansion direction and expansion mode of S. alterniflora were further analyzed. The main results obtained were as follows: (a) SENTINEL‐2 images with red‐edge bands had obvious advantages in vegetation community extraction as compared to LANDSAT‐8 images (SENTINEL‐2, OA = 82.86%, kappa coefficient = 0.79; LANDSAT‐8, OA = 78.77%, kappa coefficient = 0.74). (b) The expansion pattern of the S. alterniflora community became spatially continuous, more regularized, and aggregated over time. (c) The expansion in the north shore mainly faced toward the sea, and the south bank mainly faced toward the land, and this phenomenon was closely related to the sedimentation of the Yellow River Delta. Marginal and external expansion both occurred, but marginal expansion predominated. The results have important theoretical and scientific value for the environmental protection and sustainable development of the entire Yellow River Delta.
Comparison of arterial supercharging and venous superdrainage on improvement of survival of the extended perforator flap in rats
Authors: Wang Xin , Pan Jiadong , Xiao Dongchao , Li Miaozhong , Huang Tianxiang , Lu Chenlin , Lineaweaver William C. , Chen Hong , Yang Huilin
Published: October 2020

Background

Arterial supercharging and venous superdrainage have been the commonly used vascular augmentation techniques for resolving partial loss of flaps in reconstructive surgery. It remains controversial which one of them is more effective in improving flap survival. The purpose of this study was to compare the effect of distal venous superdrainage and arterial supercharging on the survival of an extended dorsal perforator flap in rats.

Materials and Methods

Sixty Sprague–Dawley rats were randomly divided into three groups (n = 20 in each group). An extended dorsal perforator flap with the size of 3 × 12 cm based on the deep circumflex iliac artery and vein was elevated in each rat. In arterial supercharging group, the thoracodorsal artery was retained as the distal supercharging vessel; In venous superdrainage group, the thoracodorsal vein was retained as the distal superdrainage vessel. In control group, no other arteries and veins were retained except the main vascular pedicle. On the seventh day after operation, the survival area of flap was calculated as a percentage of viable area to the total flap. Vascular changes in the choke zones were assessed by angiography. Microvascular density and diameter were assessed via immunohistochemistry staining of CD31 on the fifth day after operation.

Results

The flap survival area in arterial supercharging group was significantly higher than that in venous superdrainage group (98.9 ± 0.8% vs. 81.5 ± 3.5%, p < .001). By gross observation, the extent of dilation of choke zone vessels in venous superdrainage group was smaller compared with that in arterial supercharging group. The density of CD31‐positive vessels and the diameter of choke zone vessels in arterial supercharging group were significantly larger than that in venous superdrainage group (23.4 ± 4.6 mm−2 vs. 13.1 ± 4.2 mm−2, p < .05; and 37.5 ± 5.8 μm vs. 27.8 ± 4.9 μm, p < .05).

Conclusion

Compared with venous superdrainage, distal arterial supercharging in the potential territory resulted in better survival of an extended dorsal perforator flap in a rat model.
HDAC3i‐Finder: A Machine Learning‐based Computational Tool to Screen for HDAC3 Inhibitors
Authors: Li Shan , Ding Yu , Chen Miaomiao , Chen Ya , Kirchmair Johannes , Zhu Zihao , Wu Song , Xia Jie
Published: October 2020

Histone deacetylase 3 (HDAC3) is a potential drug target for treatment of human diseases such as cancer, chronic inflammation, neurodegenerative diseases and diabetes. Machine learning (ML) as an essential cheminformatics approach has been widely used for QSAR modeling. However, none of them has been applied to HDAC3. To this end, we carefully compiled a set of 1098 compounds from the ChEMBL database that have been assayed against HDAC3 and calculated three different sets of molecular features for each compound, i. e. two‐dimensional Mordred descriptors, MACCS keys (166 bits) and Morgan2 fingerprints (1024 bits). Five ML classifiers, i. e. k‐Nearest Neighbour (KNN), Support Vector Machine (SVM), Random forest (RF), eXtreme Gradient Boosting (XGBoost) and Deep Neural Network (DNN) were trained on each feature set and optimized for classification. A total of 15 models were generated and carefully compared, among which the best‐performing one was the XGBoost model based on the Morgan2 fingerprints, i. e. XGBoost_morgan2. Evaluated on a well‐curated benchmarking set named MUBD‐HDAC3, this model achieved a high early ROC enrichment (ROCE0.5 %: 41.02). A further retrospective screening of an annotated chemical library in PubChem demonstrated that the best model could identify 8 novel‐scaffold HDAC3 inhibitors while assaying only 1 % of the compounds. To make this model accessible for the scientific community, we developed a python GUI application named HDAC3i‐Finder to facilitate prospective screening for HDAC3 inhibitors. The source code of HDAC3i‐Finder is available at https://github.com/jwxia2014/HDAC3i‐Finder.
Solution‐processed graphene oxide coatings for enhanced heat transfer during dropwise condensation of steam
Authors: Colusso Elena , Tancon Marco , Cazzola Lorenzo , Parin Riccardo , Agnoli Stefano , De Boni Francesco , Pelizzo Maria Guglielmina , Della Gaspera Enrico , Del Col Davide , Martucci Alessandro
Published: October 2020

Hydrophobic coatings have the ability to promote dropwise condensation on metal surfaces. In this work, reduced graphene oxide coatings are fabricated by dip coating copper substrates into a graphene oxide colloidal suspension, followed by thermal reduction. The formation of reduced graphene oxide is demonstrated by Raman and X‐ray photoelectron spectroscopy characterizations, while scanning electron microscopy, atomic force microscopy and dynamic water contact angle analyses are employed to verify the morphology and the wettability of the coatings. The prepared coatings demonstrate applicability in the promotion of dropwise condensation of pure steam, with an 8‐fold enhancement of the heat transfer coefficient compared to film‐wise condensation. In addition, durability of the reduced graphene oxide coatings of more than 100 hours in the tested condition is reported.
Synthetic advances of internally nanostructured polymer particles: From and beyond block copolymer
Authors: Pan Xuefeng , Mei Shilin , Lu Yan , Yuan Jiayin
Published: October 2020

Polymer particles with internal nanostructures for versatile applications in many fields have attracted widespread attention. Among the diverse synthetic strategies toward polymer particles, polymer assembly in solution or melt is one of the most powerful methods to fabricate various hierarchically nanostructured materials in different length scales. In the review, we summarized the recent advances of several significant synthetic strategies of polymer particles with unique internal structures: (1) the principle of solvent exchange‐induced either self‐organized or scalable flash nanoprecipitation, (2) emulsion‐solvent evaporation by engineering the interfacial interaction between the emulsion droplet and medium, (3) template‐assisted method, and (4) polymerization‐induced assembly method. In each part, we systematically describe key factors such as interfacial relationship, solvent properties, and chemical nature of polymer that dictate the formation and evolution of their morphology. Finally, we discussed remaining issues of nanostructured polymer assemblies and their potential for future applications.
Flexible Co3O4/TiO2 monolithic catalysts for low‐temperature and long‐term stable CO oxidation
Authors: Tang Xinyue , Wang Junchao , Ma Yonghui , Li Jing , Zhang Xinglai , La Peiqing , Liu Baodan
Published: October 2020

The development of efficient monolithic catalysts and their fabrication methods for low‐temperature and long‐term stable CO oxidation always remains a challenge for both fundamental research and technological application. In this work, an innovative synthetic strategy to in‐situ integrate Co3O4/TiO2 monolithic catalysts on flexible Ti mesh substrate through multi‐step processes was demonstrated. The in‐situ grown catalysts show strong substrate adhesion, large surface areas and a complete CO conversion temperature of 105°C, which is superior or comparative to most noble metal catalysts. The in‐situ grown Co3O4/TiO2 catalysts on Ti mesh also exhibit excellent long‐term stability that is critically important for industrial application. It is expected that the in‐situ synthesis strategy of well‐defined Co3O4/TiO2 monolithic catalysts on flexible mesh substrate can be extended to the development of a variety of oxide‐based monolithic catalysts towards diverse catalysis applications.
Selective serotonin reuptake inhibitor or serotonin‐norepinephrine reuptake inhibitors and epidemiological characteristics associated with prenatal diagnosis of congenital heart disease
Authors: Melov Sarah J. , Shetty Prayatna Singh , Pasupathy Dharmintra , Kirby Adrienne , Sholler Gary F. , Winlaw David S. , Alahakoon Thushari I.
Published: October 2020

Objective

Identify early pregnancy associations of congenital heart disease (CHD) in a multiethnic cohort.

Methods

This retrospective observational cohort study compared the general obstetric population to women who gave birth at a referral centre in Australia between 2012 and 2017, after 20 weeks' of gestation, with a pregnancy affected by CHD. We defined mood disorder and anxiety as a history of self‐reported or medically diagnosed anxiety, depression, postpartum depression or bipolar disorder.

Results

We compared epidemiological factors between 30 842 general obstetric patients and 470 obstetric patients with a foetus affected by CHD. Multivariate analysis showed independent associations between CHD and use of selective serotonin reuptake inhibitors (SSRIs) or serotonin‐norepinephrine reuptake inhibitors (SNRIs) in the first trimester (relative risk [RR] 4.14, 95% CI 2.58‐6.65), history of anxiety or mood disorder with no SSRI/SNRI first trimester (RR 2.20, 95% CI 1.77‐2.74), folate and/or pregnancy multivitamin use in the first trimester (RR 0.69, 95% CI 0.55‐0.87) and increased risk with maternal age >40 years (RR 2.30, 95% CI 1.57‐3.38).

Conclusions

Our data show maternal mood disorders with and without SSRI or SNRI use, maternal age >40 years and lack of multivitamin/folate use to be independently associated with CHD in pregnancy.
Outcomes following the detection of fetal edema in early pregnancy prior to non‐invasive prenatal testing
Authors: Ramkrishna Jayshree , Menezes Melody , Humnabadkar Kedar , Tse Cheryl , Maxfield Maria J. , da Silva Costa Fabricio , Rolnik Daniel L. , Meagher Simon
Published: October 2020

Objective

To investigate the incidence of structural and chromosomal abnormalities in cases of fetal edema on early ultrasound prior to non‐invasive prenatal testing (NIPT).

Methods

A retrospective study of women undergoing pre‐NIPT ultrasound with fetal crown‐rump length (CRL) of 28 to 44 mm was conducted at a tertiary obstetric ultrasound clinic in Melbourne, Australia. Cases of reported fetal edema were included, and subclassified as isolated nuchal edema (>2.2 mm) or generalized edema/hydrops by two operators blinded to outcomes.

Results

We identified 104 cases of fetal edema. Nuchal edema and generalized edema were present in 40 (38.5%) and 64 (61.5%) cases, respectively. Relevant chromosomal anomalies were identified in 19.2% (20/104), occurring in 10.0% (4/40) of the nuchal edema and 25.0% (16/64) of the generalized edema/hydrops cases. Structural anomalies with normal karyotype occurred in four (3.8%) additional cases. Miscarriage occurred in four cases (3.8%) and termination of pregnancy in 18 cases (17.3%). Among cases that reached the 11 to 13+6 weeks ultrasound, the edema resolved in 81.9% and these cases had less adverse outcomes than those with NT≥3.5 mm (10.9% vs 76.5%, P < .001).

Conclusions

Fetal edema in early pregnancy is associated with a high incidence of structural and/or chromosomal abnormalities; these rates increase with progressive severity.
Direct healthcare costs of chronic kidney disease management in Italy: What cost‐savings can be achieved with higher biosimilar uptake and more appropriate use of erythropoiesis‐stimulating agents?
Authors: Ingrasciotta Ylenia , Sultana Janet , Formica Dario , Ientile Valentina , Aiello Andrea , Chinellato Alessandro , Tari Daniele Ugo , Gini Rosa , Pastorello Maurizio , Scondotto Salvatore , Cananzi Pasquale , Traversa Giuseppe , Rossi Mariangela , Santoro Domenico , Trifirò Gianluca ,   the Italian Biosimilars Network (I‐BioNetwork)
Published: October 2020

Purpose

Erythropoiesis‐stimulating agents (ESAs), are used for treating chronic kidney disease (CKD)‐related anemia, contributing to CKD costs. The study was aimed at investigating direct healthcare costs of CKD patients treated with ESAs and the potential savings achievable by increasing the use of biosimilars and preventing inappropriate ESA use.

Methods

A multi‐center, cohort study was conducted using claims databases of five large Italian geographic areas. Yearly mean direct healthcare costs per patient were estimated, stratifying by CKD stage. The total yearly cost and potential savings related to ESA use were estimated: (a) considering 25/50/75% of originator ESA substitution with biosimilars; (b) eliminating inappropriate ESA dispensing.

Results

During the study period, the ESA‐related yearly mean cost represented 17% of total yearly costs in stage I‐III, decreasing to 13% in stage IV‐V and 6% in dialysis. Among originator users, assuming a 25% of biosimilar uptake, the annual cost‐savings of ESA treatment would represent 10.5% of total ESA costs in CKD stage I‐V and 7.7% in dialysis. Among incident ESA users for which hemoglobin levels were available, 9% started inappropriately ESA treatment, increasing to 62.0% during the first year of maintenance therapy. Hypothesizing prevention of the first inappropriate ESA dispensing, the total yearly cost‐savings would amount to €35 772, increasing to €167 641 eliminating the inappropriate dispensing during maintenance therapy.

Conclusions

Higher use of lowest cost ESA, prevention of inappropriate ESA use as well as other strategies aimed at slowing down the progressive renal impairment are essential for minimizing clinical and economic burden of CKD.
Synthesis and properties of thermoplastic and dissolvable polysiloxanes containing polyhedral oligomeric silsesquioxane
Authors: Guo Ruilu , Liu Yuemin , Zhou Lixia , Li Na , Chen Guangxin , Zhou Zheng , Li Qifang
Published: October 2020

There are many benefits associated with thermoplastic silicones, but very few examples exist: silicone resins or rubbers are normally thermosets. In this article, a facile and efficient approach was reported to prepare thermoplastic silicone by introducing a bulky side siloxane group. Monofunctional polyhedral oligomeric silsesquioxane (POSS), as the bulky siloxane group, was grafted onto the linear polysiloxane backbone via thiol–ene click reaction, endowing the liquid polysiloxane with thermoplastic nature. The POSS‐grafted polysiloxane could be remolded by a hot‐melting or solution casting process. It was worth noting that the novel thermoplastic silicone was composed of both linear siloxane main chains and siloxane side groups, which was distinctly different from previous researches on thermoplastic silicones consisted of siloxane main chains and organic side groups. Thermal analysis, rheological characterization and molecular dynamics simulation results revealed the thermoplastic properties of POSS‐grafted polysiloxane depended on the bulky POSS's hindrance to the movement of the polymer backbone rather than the interaction between the organic side groups.
Tuning the binding interface between Machupo virus glycoprotein and human transferrin receptor
Authors: Sjöström Dick J , Lundgren Anneli , Garforth Scott J , Bjelic Sinisa
Published: October 2020

Machupo virus, known to cause hemorrhagic fevers, enters human cells via binding with its envelope glycoprotein to transferrin receptor 1 (TfR). Similarly, the receptor interactions have been explored in biotechnological applications as a molecular system to ferry therapeutics across the cellular membranes and through the impenetrable blood–brain barrier that effectively blocks any such delivery into the brain. Study of the experimental structure of Machupo virus glycoprotein 1 (MGP1) in complex with TfR and glycoprotein sequence homology has identified some residues at the interface that influence binding. There are, however, no studies that have attempted to optimize the binding potential between MGP1 and TfR. In pursuits for finding therapeutic solutions for the New World arenaviruses, and to gain a greater understanding of MGP1 interactions with TfR, it is crucial to understand the structure–sequence relationship driving the interface formation. By displaying MGP1 on yeast surface we have examined the contributions of individual residues to the binding of solubilized ectodomain of TfR. We identified MGP1 binding hot spot residues, assessed the importance of posttranslational N‐glycan modifications, and used a selection with random mutagenesis for affinity maturation. We show that the optimized MGP1 variants can bind more strongly to TfR than the native MGP1, and there is an MGP1 sequence that retains binding in the absence of glycosylation, but with the addition of further amino acid substitutions. The engineered variants can be used to probe cellular internalization or the blood‐brain barrier crossing to achieve greater understanding of TfR mediated internalization.
Examination of Metoprolol Pharmacokinetics and Pharmacodynamics Across CYP2D6 Genotype‐Derived Activity Scores
Authors: Thomas Cameron D. , Mosley Scott A. , Kim Sarah , Lingineni Karthik , El Rouby Nihal , Langaee Taimour Y. , Gong Yan , Wang Danxin , Schmidt Siegfried O. , Binkley Philip F. , Estores David S. , Feng Kairui , Kim Hyewon , Kinjo Minori , Li Zhichuan , Fang Lanyan , Chapman Arlene B. , Cooper-DeHoff Rhonda M. , Gums John G. , Hamadeh Issam S. , Zhao Liang , Schmidt Stephan , Frye Reginald F. , Johnson Julie A. , Cavallari Larisa H.
Published: October 2020

Recent CYP2D6 phenotype standardization efforts by CYP2D6 activity score (AS) are based on limited pharmacokinetic (PK) and pharmacodynamic (PD) data. Using data from two independent clinical trials of metoprolol, we compared metoprolol PK and PD across CYP2D6 AS with the goal of determining whether the PK and PD data support the new phenotype classification. S‐metoprolol apparent oral clearance (CLo), adjusted for clinical factors, was correlated with CYP2D6 AS (P < 0.001). The natural log of CLo was lower with an AS of 1 (7.6 ± 0.4 mL/minute) vs. 2–2.25 (8.3 ± 0.6 mL/minute; P = 0.012), similar between an AS of 1 and 1.25–1.5 (7.8 ± 0.5 mL/minute; P = 0.702), and lower with an AS of 1.25–1.5 vs. 2–2.25 (P = 0.03). There was also a greater reduction in heart rate with metoprolol among study participants with AS of 1 (−10.8 ± 5.5) vs. 2–2.25 (−7.1 ± 5.6; P < 0.001) and no significant difference between those with an AS of 1 and 1.25–1.5 (−9.2 ± 4.7; P = 0.095). These data highlight linear trends among CYP2D6 AS and metoprolol PK and PD, but inconsistencies with the phenotypes assigned by AS based on the current standards. Overall, this case study with metoprolol suggests that utilizing CYP2D6 AS, instead of collapsing AS into phenotype categories, may be the most precise approach for utilizing CYP2D6 pharmacogenomics in clinical practice.
Hydrogen in As‐Grown and Annealed ZnO Films Grown by Atomic Layer Deposition
Authors: Guziewicz Elzbieta , Wozniak Wojciech , Mishra Sushma , Jakiela Rafal , Guziewicz Marek , Ivanov Vitalij Yu , Lusakowska Elzbieta , Schifano Ramon
Published: October 2020

The origin of unintentional hydrogen incorporation in ZnO films grown by thermal atomic layer deposition is investigated by comparing layers deposited using H2O and D2O as oxygen precursors. Secondary ion mass spectroscopy measurements of as‐grown and 800 °C annealed layers provide evidence that the hydrogen contribution originating from the oxygen precursor is weakly chemically bound and is mostly removed by rapid thermal annealing conducted at 800 °C for 3 min in oxygen atmosphere. On the other hand, the remaining hydrogen introduced by ethyl groups originating from the metalorganic zinc precursor withstands such treatment.