bluuebunny/crossref_metadata_2025 huggingface dataset:
Personalized in vitro Extracellular Matrix Models of Collagen VI-Related Muscular Dystrophies
Authors: Almici Enrico , Chiappini Vanessa , López-Márquez Arístides , Badosa Carmen , Blázquez Blanca , Caballero David , Montero Joan , Natera-de Benito Daniel , Nascimento Andrés , Roldán Mònica , Lagunas Anna , Jiménez-Mallebrera Cecilia , Samitier Josep
Published: April 2022

Collagen VI-related dystrophies (COL6-RDs) are a group of rare congenital neuromuscular dystrophies that represent a continuum of overlapping clinical phenotypes that go from the milder Bethlem myopathy (BM) to the severe Ullrich congenital muscular dystrophy, for which there is no effective treatment. Mutations in one of the three Collagen VI genes alter the incorporation of this protein into the extracellular matrix (ECM), affecting the assembly and the structural integrity of the whole fibrillar network. Clinical hallmarks of COL6-RDs are secondary to the ECM disruption and include muscle weakness, proximal joint contractures, and distal hyperlaxity. Although some traits have been identified in patients’ ECMs, a correlation between the ECM features and the clinical phenotype has not been established, mainly due to the lack of predictive and reliable models of the pathology. Herein, we engineered a new personalized pre-clinical model of COL6-RDs using cell-derived matrices (CDMs) technology to better recapitulate the complexity of the native scenario. We found that CDMs from COL6-RD patients presented alterations in ECM structure and composition, showing a significantly decreased Collagen VI secretion, especially in the more severe phenotypes, and a decrease in Fibrillin-1 inclusion. Next, we examined the Collagen VI-mediated deposition of Fibronectin in the ECM, finding a higher alignment, length, width, and straightness than in patients with COL6-RDs. Overall, these results indicate that CDMs models are promising tools to explore the alterations that arise in the composition and fibrillar architecture due to mutations in Collagen VI genes, especially in early stages of matrix organization. Ultimately, CDMs derived from COL6-RD patients may become relevant pre-clinical models, which may help identifying novel biomarkers to be employed in the clinics and to investigate novel therapeutic targets and treatments.
Recent Advances in Multifunctional Hydrogels for the Treatment of Osteomyelitis
Authors: Xin Weiwei , Gao Yingjian , Yue Bing
Published: April 2022

Osteomyelitis (OM), a devastating disease caused by microbial infection of bones, remains a major challenge for orthopedic surgeons. Conventional approaches for prevention and treatment of OM are unsatisfactory. Various alternative strategies have been proposed, among which, hydrogel-based strategies have demonstrated potential due to their unique properties, including loadable, implantable, injectable, printable, degradable, and responsive to stimuli. Several protocols, including different hydrogel designs, selection of antimicrobial agent, co-administration of bone morphogenetic protein 2 (BMP 2), and nanoparticles, have been shown to improve the biological properties, including antimicrobial effects, osteo-induction, and controlled drug delivery. In this review, we describe the current and future directions for designing hydrogels and their applications to improve the biological response to OM in vivo.
Adhesive Materials Inspired by Barnacle Underwater Adhesion: Biological Principles and Biomimetic Designs
Authors: Gan Kesheng , Liang Chao , Bi Xiangyun , Wu Jizhe , Ye Zonghuang , Wu Wenjian , Hu Biru
Published: April 2022

Wet adhesion technology has potential applications in various fields, especially in the biomedical field, yet it has not been completely mastered by humans. Many aquatic organisms (e.g., mussels, sandcastle worms, and barnacles) have evolved into wet adhesion specialists with excellent underwater adhesion abilities, and mimicking their adhesion principles to engineer artificial adhesive materials offers an important avenue to address the wet adhesion issue. The crustacean barnacle secretes a proteinaceous adhesive called barnacle cement, with which they firmly attach their bodies to almost any substrate underwater. Owing to the unique chemical composition, structural property, and adhesion mechanism, barnacle cement has attracted widespread research interest as a novel model for designing biomimetic adhesive materials, with significant progress being made. To further boost the development of barnacle cement–inspired adhesive materials (BCIAMs), it is necessary to systematically summarize their design strategies and research advances. However, no relevant reviews have been published yet. In this context, we presented a systematic review for the first time. First, we introduced the underwater adhesion principles of natural barnacle cement, which lay the basis for the design of BCIAMs. Subsequently, we classified the BCIAMs into three major categories according to the different design strategies and summarized their research advances in great detail. Finally, we discussed the research challenge and future trends of this field. We believe that this review can not only improve our understanding of the molecular mechanism of barnacle underwater adhesion but also accelerate the development of barnacle-inspired wet adhesion technology.
Reproducibility of Bacterial Cellulose Nanofibers Over Sub-Cultured Generations for the Development of Novel Textiles
Authors: Wood Jane , van der Gast Christopher , Rivett Damian , Verran Joanna , Redfern James
Published: April 2022

The textile industry is in crisis and under pressure to minimize the environmental impact on its practices. Bacterial cellulose (BC), a naturally occurring form of cellulose, displays properties superior to those of its cotton plant counterpart, such as enhanced purity, crystallinity, tensile strength, and water retention and is thus suitable for an array of textile applications. It is synthesized from a variety of microorganisms but is produced in most abundance by Komagataeibacter xylinus. K. xylinus is available as a type strain culture and exists in the microbial consortium commonly known as Kombucha. Whilst existing literature studies have described the effectiveness of both K. xylinus isolates and Kombucha in the production of BC, this study investigated the change in microbial communities across several generations of sub-culturing and the impact of these communities on BC yield. Using Kombucha and the single isolate strain K. xylinus as inocula in Hestrin and Schramm liquid growth media, BC pellicles were propagated. The resulting pellicles and residual liquid media were used to further inoculate fresh liquid media, and this process was repeated over three generations. For each generation, the thickness of the pellicles and their appearance under SEM were recorded. 16S rRNA sequencing was conducted on both pellicles and liquid media samples to assess changes in communities. The results indicated that the genus Komagataeibacter was the most abundant species in all samples. Cultures seeded with Kombucha yielded thicker cellulose pellicles than those seeded with K. xylinus, but all the pellicles had similar nanofibrillar structures, with a mix of liquid and pellicle inocula producing the best yield of BC after three generations of sub-culturing. Therefore, Kombucha starter cultures produce BC pellicles which are more reproducible across generations than those created from pure isolates of K. xylinus and could provide a reproducible sustainable model for generating textile materials.
Detection and Localization of Solid Tumors Utilizing the Cancer-Type-Specific Mutational Signatures
Authors: Wang Ziyu , Zhang Tingting , Wu Wei , Wu Lingxiang , Li Jie , Huang Bin , Liang Yuan , Li Yan , Li Pengping , Li Kening , Wang Wei , Guo Renhua , Wang Qianghu
Published: April 2022

Accurate detection and location of tumor lesions are essential for improving the diagnosis and personalized cancer therapy. However, the diagnosis of lesions with fuzzy histology is mainly dependent on experiences and with low accuracy and efficiency. Here, we developed a logistic regression model based on mutational signatures (MS) for each cancer type to trace the tumor origin. We observed MS could distinguish cancer from inflammation and healthy individuals. By collecting extensive datasets of samples from ten tumor types in the training cohort (5,001 samples) and independent testing cohort (2,580 samples), cancer-type-specific MS patterns (CTS-MS) were identified and had a robust performance in distinguishing different types of primary and metastatic solid tumors (AUC:0.76 ∼ 0.93). Moreover, we validated our model in an Asian population and found that the AUC of our model in predicting the tumor origin of the Asian population was higher than 0.7. The metastatic tumor lesions inherited the MS pattern of the primary tumor, suggesting the capability of MS in identifying the tissue-of-origin for metastatic cancers. Furthermore, we distinguished breast cancer and prostate cancer with 90% accuracy by combining somatic mutations and CTS-MS from cfDNA, indicating that the CTS-MS could improve the accuracy of cancer-type prediction by cfDNA. In summary, our study demonstrated that MS was a novel reliable biomarker for diagnosing solid tumors and provided new insights into predicting tissue-of-origin.
Homozygous Loss of Septin12, but not its Haploinsufficiency, Leads to Male Infertility and Fertilization Failure
Authors: Chen Haixia , Li Peng , Du Xiaoling , Zhao Yiding , Wang Lingling , Tian Ye , Song Xueru , Shuai Ling , Bai Xiaohong , Chen Lingyi
Published: April 2022

The SEPTIN12 gene has been associated with male infertility. Male Septin12+/− chimera mice were infertile, supporting the prevailing view that SEPTIN12 haploinsufficiency causes male infertility. In this study, we identified a heterozygous mutation on SEPTIN12, c.72C>A (p.Cys24Ter) in the male partner of a patient couple, who had a previous fertilization failure (FF) after intracytoplasmic sperm injection (ICSI) and became pregnant after ICSI together with artificial oocyte activation (AOA). To investigate the role of SEPTIN12 in FF and oocyte activation, we constructed Septin12 knockout mice. Surprisingly, Septin12−/− male mice, but not Septin12+/− male mice, are infertile, and have reduced sperm counts and abnormal sperm morphology. Importantly, AOA treatment enhances the 2-cell embryo rate of ICSI embryos injected with Septin12−/− sperm, indicating that FF caused by male Septin12 deficiency is overcome by AOA. Mechanistically, loss of PLCζ around the acrosome might be the reason for FF of Septin12−/− sperm. Taken together, our data indicated that homozygous knockout of Septin12, but not Septin12 haploinsufficiency, leads to male infertility and FF.
KIF13A—A Key Regulator of Recycling Endosome Dynamics
Authors: Thankachan Jerrin Mathew , Setty Subba Rao Gangi
Published: April 2022

Molecular motors of the kinesin superfamily (KIF) are a class of ATP-dependent motor proteins that transport cargo, including vesicles, along the tracks of the microtubule network. Around 45 KIF proteins have been described and are grouped into 14 subfamilies based on the sequence homology and domain organization. These motors facilitate a plethora of cellular functions such as vesicle transport, cell division and reorganization of the microtubule cytoskeleton. Current studies suggest that KIF13A, a kinesin-3 family member, associates with recycling endosomes and regulates their membrane dynamics (length and number). KIF13A has been implicated in several processes in many cell types, including cargo transport, recycling endosomal tubule biogenesis, cell polarity, migration and cytokinesis. Here we describe the recent advances in understanding the regulatory aspects of KIF13A motor in controlling the endosomal dynamics in addition to its structure, mechanism of its association to the membranes, regulators of motor activity, cell type-specific cargo/membrane transport, methods to measure its activity and its association with disease. Thus, this review article will provide our current understanding of the cell biological roles of KIF13A in regulating endosomal membrane remodeling.
Placental Abnormalities are Associated With Specific Windows of Embryo Culture in a Mouse Model
Authors: Vrooman Lisa A. , Rhon-Calderon Eric A. , Suri Kashviya V. , Dahiya Asha K. , Lan Yemin , Schultz Richard M. , Bartolomei Marisa S.
Published: April 2022

Assisted Reproductive Technologies (ART) employ gamete/embryo handling and culturein vitroto produce offspring. ART pregnancies have an increased risk of low birth weight, abnormal placentation, pregnancy complications, and imprinting disorders. Embryo culture induces low birth weight, abnormal placental morphology, and lower levels of DNA methylation in placentas in a mouse model of ART. Whether preimplantation embryos at specific stages of development are more susceptible to these perturbations remains unresolved. Accordingly, we performed embryo culture for several discrete periods of preimplantation development and following embryo transfer, assessed fetal and placental outcomes at term. We observed a reduction in fetal:placental ratio associated with two distinct windows of preimplantation embryo development, one prior to the morula stage and the other from the morula to blastocyst stage, whereas placental morphological abnormalities and reduced imprinting control region methylation were only associated with culture prior to the morula stage. Extended culture to the blastocyst stage also induces additional placental DNA methylation changes compared to embryos transferred at the morula stage, and female concepti exhibited a higher loss of DNA methylation than males. By identifying specific developmental windows of susceptibility, this study provides a framework to optimize further culture conditions to minimize risks associated with ART pregnancies.
Spatiotemporal Dynamic Regulation of Organelles During Meiotic Development, Insights From Fungi
Authors: Hernández-Sánchez Fernando , Peraza-Reyes Leonardo
Published: April 2022

Eukaryotic cell development involves precise regulation of organelle activity and dynamics, which adapt the cell architecture and metabolism to the changing developmental requirements. Research in various fungal model organisms has disclosed that meiotic development involves precise spatiotemporal regulation of the formation and dynamics of distinct intracellular membrane compartments, including peroxisomes, mitochondria and distinct domains of the endoplasmic reticulum, comprising its peripheral domains and the nuclear envelope. This developmental regulation implicates changes in the constitution and dynamics of these organelles, which modulate their structure, abundance and distribution. Furthermore, selective degradation systems allow timely organelle removal at defined meiotic stages, and regulated interactions between membrane compartments support meiotic-regulated organelle dynamics. This dynamic organelle remodeling is implicated in conducting organelle segregation during meiotic differentiation, and defines quality control regulatory systems safeguarding the inheritance of functional membrane compartments, promoting meiotic cell rejuvenation. Moreover, organelle remodeling is important for proper activity of the cytoskeletal system conducting meiotic nucleus segregation, as well as for meiotic differentiation. The orchestrated regulation of organelle dynamics has a determinant contribution in the formation of the renewed genetically-diverse offspring of meiosis.
Chloride Salt Purification by Reaction With Thionyl Chloride Vapors to Remove Oxygen, Oxygenated Compounds, and Hydroxides
Authors: McFarlane Joanna , Del Cul Guillermo D. , Massengale Jordan R. , Mayes Richard T. , Robb Kevin R. , Sulejmanovic Dino
Published: April 2022

Molten chloride salts (including MgCl2, KCl, NaCl, and ZnCl2) are being considered for heat transfer media for renewable (solar) and nuclear power generators, as fuel carrier for nuclear reactors, and as thermal energy storage media. Impurities such as oxygen, hydroxides, moisture, and sulfur are known to negatively influence the corrosion of materials in contact with the salt (e.g., structural metals). Commercially available chloride salts come with a range of impurities. Before using the chloride salts at high temperature, it is desirable to remove the impurities to increase the performance of the salt and reduce corrosion. In this study, we tested the use of thionyl chloride vaporized into a stream of argon to react with oxygenated impurities in a mixture of MgCl2-KCl-NaCl, removing them as HCl and SO2. The reagent was bubbled through the salt when both above and below the melting point. The reaction was followed using thermocouple data from the salt and by Fourier transform infrared (FTIR) spectroscopy on the exhaust of the reactor. The reaction kinetics were followed by comparing the peaks from SO2 product to SOCl2 reagent in the FTIR spectra. The purity of the salt was assessed at the end of the purification process by x-ray diffraction and inductively coupled plasma analysis. Although the process was effective in removing the oxygen content of the mixture, ternary compounds were formed in the process, including KNiCl3 and KMgCl3. The nickel in KNiCl3 came from the reaction between the salt and the nickel vessel. Thus, these experiments suggest that improvements to the process must be made before using SOCl2 vapors for the purification of chloride salts.
Advances of Synthesis Methods for Porous Silicon-Based Anode Materials
Authors: Zhang Fan , Zhu Wenqiang , Li Tingting , Yuan Yuan , Yin Jiang , Jiang Jianhong , Yang Lishan
Published: April 2022

Silicon (Si)-based anode materials have been the promising candidates to replace commercial graphite, however, there are challenges in the practical applications of Si-based anode materials, including large volume expansion during Li+ insertion/deinsertion and low intrinsic conductivity. To address these problems existed for applications, nanostructured silicon materials, especially Si-based materials with three-dimensional (3D) porous structures have received extensive attention due to their unique advantages in accommodating volume expansion, transportation of lithium-ions, and convenient processing. In this review, we mainly summarize different synthesis methods of porous Si-based materials, including template-etching methods and self-assembly methods. Analysis of the strengths and shortages of the different methods is also provided. The morphology evolution and electrochemical effects of the porous structures on Si-based anodes of different methods are highlighted.
Impact of Location on Predator Control Preference Patterns
Authors: Stanger Melissa E. , Slagle Kristina M. , Bruskotter Jeremy T.
Published: April 2022

In recent decades, interactions with carnivores have increased in suburban and urban areas. However, it is unknown how predator control preferences of urban, suburban, and rural residents compare. We sought to characterize predator control preferences regarding interactions with bobcats (Lynx rufus) and coyotes (Canis latrans), and compare these preferences among people living in urban, suburban, and rural areas. We also sought to determine the factors that predicted the likelihood of respondents changing their predator control preference. We conducted cross-sectional surveys of adult residents of the United States and the state of Ohio and embedded randomly assigned carnivore interaction scenarios in which respondents were asked to choose their preferred predator control in response to each scenario. We found that when both scenarios took place in an agricultural location, respondents became significantly more sensitive to changes in the severity (i.e., they were more likely to switch their preferred method of predator control). Subjects overwhelmingly indicated a preference for non-lethal forms of predator control. Specifically, 71.8% of respondents preferred non-lethal in response to both scenarios, 18.5% gave mixed responses (i.e., preferred lethal in response to one of the scenarios but non-lethal in response to the other scenario), and only 9.7% preferred lethal predator control in response to both scenarios. The tendency to prefer only non-lethal methods decreased along the urban-rural gradient such that 78.5% of urban respondents expressed a consistent preference for non-lethal forms of control, compared with 72.8% of suburban respondents, and 51.3% rural respondents. This suggests that most urban and suburban residents view lethal predator control methods as simply inappropriate—at least for the scenarios described. In practice, the management of human-carnivore interactions in urban and suburban areas is complicated by a variety of factors (e.g., the presence and density of humans and their pets) which reduce the flexibility of wildlife managers in these areas. Additionally, management options may be further restricted by the preferences of residents, especially given that management is likely to be more visible in these areas. Strong preferences against lethal control in urban and suburban settings may incentivize the development of novel methods for controlling human-carnivore conflicts in the future.
Echocardiographic Normal Reference Ranges for Non-invasive Myocardial Work Parameters in Pediatric Age: Results From an International Multi-Center Study
Authors: Sabatino Jolanda , Leo Isabella , Strangio Antonio , Bella Sabrina La , Borrelli Nunzia , Avesani Martina , Josen Manjit , Paredes Josefa , Piccinelli Enrico , Sirico Domenico , Pergola Valeria , Fraisse Alain , De Rosa Salvatore , Indolfi Ciro , Di Salvo Giovanni
Published: April 2022

Aims

This international multi-center study aimed to demonstrate the feasibility and reliability of non-invasive myocardial work (MW) parameters in the pediatric population, and to provide normal reference ranges for this useful echocardiographic tool in this specific subset of patients.

Methods and Results

In this retrospective multi-center study involving three pediatric laboratories, 150 healthy children and adolescents (mean age of 10.6 ± 4.5, 91 males) were enrolled. A complete echocardiographic examination has been performed, including global longitudinal strain (GLS) assessment. The following parameters of non-invasive MW have been obtained through a dedicated software: global work index (GWI), global constructive work (GCW), global work waste (GWW), and global work efficiency (GWE), using left ventricular (LV) strain loops and non-invasive brachial artery cuff pressure values. The lowest expected values were for GWI 1,723 mmHg% in males and 1,682 mmHg% in females, for GCW 2,089 and 2,106 mmHg%, for GWE 95.9 and 95.5% whereas the highest expected value for GWW was 78 mmHg% in men and 90 mmHg% in women. The univariable and multivariable analysis showed significant associations between either GWI or GCW with SBP (β coefficient = 0.446, p < 0.001; β coefficient = 0.456, p < 0.001, respectively) and LV GLS (β coefficient = −0.268, p = 0.001; β coefficient = −0.233, p = 0.003, respectively). Inter- and intra-observer variability showed good reproducibility of non-invasive MW parameters.

Conclusion

Non-invasive MW parameters were feasible and reliable in the pediatric population. This study provided normal reference ranges of these useful echocardiographic indices.
Regional Fat Distributions Are Associated With Subclinical Right Ventricular Dysfunction in Adults With Uncomplicated Obesity
Authors: Liu Jing , Li Jing , Yu Jianqun , Xia Chunchao , Pu Huaxia , He Wenzhang , Li Xue , Zhou Xiaoyue , Tong Nanwei , Peng Liqing
Published: April 2022

Objective

Obesity is a prominent public health problem that has increased cardiovascular mortality risks. However, the specific effects of obesity, independent of comorbidities, on cardiac structure and function have not been well clarified, especially those effects on the right ventricle (RV). Cardiovascular magnetic resonance (CMR) tissue tracking can assess detailed RV mechanical features. This study aimed to evaluate RV strain using CMR in uncomplicated obese adults and assess its association with fat distributions.

Methods

A total of 49 obese patients and 30 healthy controls were included. The RV global systolic function and strain parameters based on CMR were assessed. Body fat distributions were measured with dual X-ray absorptiometry. RV function indices of obese patients were compared with those of healthy controls. Correlations among related body fat distribution parameters and RV function indices were conducted with multivariable linear regression.

Results

Compared with healthy controls, the obese group had impaired RV strain with lower global longitudinal peak strain (PS), longitudinal peak systolic strain rate (PSSR), circumferential and longitudinal peak diastolic strain rates (PDSR) (all P < 0.05), while LV and RV ejection fractions were not significantly different between the two groups (P > 0.05). Multivariable linear regression analysis demonstrated that android fat% was independently associated with longitudinal PS (β = −0.468, model R2 = 0.219), longitudinal PDSR (β = −0.487, model R2 = 0.237), and circumferential PSSR (β = −0.293, model R2 = 0.086). Trunk fat% was independently associated with longitudinal PSSR (β = −0.457, model R2 = 0.209). In addition, the strongest correlations of circumferential PDSR were BMI and gynoid fat% (β = −0.278, β = 0.369, model R2 = 0.324).

Conclusions

Extensive subclinical RV dysfunction is found in uncomplicated obese adults. BMI, as an index of overall obesity, is independently associated with subclinical RV dysfunction. In addition, central obesity (android fat and trunk fat distributions) has a negative effect on subclinical RV function, while peripheral obesity (gynoid fat distribution) may have a positive effect on it.

Clinical Trials Registration

Effect of lifestyle intervention on metabolism of obese patients based on smart phone software (ChiCTR1900026476).
Feasibility of an Automatic Ultrasonographic Image Acquisition System Associated With an Artificial Intelligence Algorithm for Real-Time Monitoring of Cardiac Motion During Cardiac Radio-Ablation
Authors: Casula Matteo , Dusi Veronica , Camps Saskia , Gringet Jérémie , Benoit Tristan , Garonna Adriano , Rordorf Roberto
Published: April 2022

Background

The management of the cardio-respiratory motion of the target and the reduction of the uncertainties related to patient's positioning are two of the main challenges that stereotactic arrhythmia radio-ablation (STAR) has to overcome. A prototype of a system was developed that can automatically acquire and interpret echocardiographic images using an artificial intelligence (AI) algorithm to calculate cardiac displacement in real-time.

Methods

We conducted a single center study enrolling consecutive patients with a history of ventricular arrhythmias (VA) in order to evaluate the feasibility of this automatic acquisition system. Echocardiographic images were automatically acquired from the parasternal and apical views with a dedicated probe. The system was designed to hold the probe fixed to the chest in the supine position during both free-breathing and short expiratory breath-hold sequences, to simulate STAR treatment. The primary endpoint was the percentage of patients reaching a score ≥2 in a multi-parametric assessment evaluating the quality of automatically acquired images. Moreover, we investigated the potential impact of clinical and demographic characteristics on achieving the primary endpoint.

Results

We enrolled 24 patients (63 ± 14 years, 21% females). All of them had a history of VA and 21 (88%) had an ICD. Eight patients (33%) had coronary artery disease, 12 (50%) had non-ischemic cardiomyopathy, and 3 had idiopathic VA. Parasternal, as well as apical images were obtained from all patients except from one, in whom parasternal view could not be collected due to the patient's inability to maintain the supine position. The primary endpoint was achieved in 23 patients (96%) for the apical view, in 20 patients (87%) for the parasternal view, and in all patients in at least one of the two views. The images' quality was maximal (i.e., score = 4) in at least one of the two windows in 19 patients (79%). Atrial fibrillation arrhythmia was the only clinical characteristics associated with a poor score outcome in both imaging windows (apical p = 0.022, parasternal p = 0.014).

Conclusions

These results provide the proof-of-concept for the feasibility of an automatic ultrasonographic image acquisition system associated with an AI algorithm for real-time monitoring of cardiac motion in patients with a history of VA.
Developing Small-Molecule Inhibitors of Protein-Protein Interactions Involved in Viral Entry as Potential Antivirals for COVID-19
Authors: Buchwald Peter
Published: April 2022

Blocking protein-protein interactions (PPIs) involved in the initiation of the cell attachment and entry of viruses is an important antiviral mechanism of action including for neutralizing antibodies. Doing it with small-molecule inhibitors (SMIs) is challenging, as it is for all other PPIs, and might require the exploration of chemical space beyond that of typical drug-like structures. However, it could lead to new antiviral agents suitable for oral administration and acting on alternative targets, considerations that are essential for the development of widely acceptable and broad-spectrum preventive or curative therapeutics. Fostemsavir, an antiretroviral that acts via blocking of the gp120–CD4 PPI, supports the feasibility of the concept. Here, a brief review of relevant drug design considerations is presented together with a summary of the progress made toward the identification of SMIs targeting the PPI between the SARS-CoV-2 spike protein and ACE2 that initiates the viral attachment and cellular entry of this coronavirus causing the COVID-19 pandemic. SMIs identified in various screening assays that were also confirmed to have antiviral activity in a live virus or pseudovirus assay with an IC50 < 30 µM so far include several organic dyes (methylene blue, Evans blue, Congo red, direct violet 1), verteporfin, DRI-C23041, and cannabigerolic and cannabidiolic acids. While specificity and activity profiles still need improvement, results so far already provide proof-of-principle evidence for the feasibility of SMIs targeting the SARS-CoV-2-S–hACE2 PPI. Methylene blue, which is approved for clinical use, is orally bioactive, and could act by multiple mechanisms of action, might have potential for repurposing for COVID-19 prevention and treatment.
A Call to Action: Using and Extending Human-Centered Design Methodologies to Improve Mental and Behavioral Health Equity
Authors: Stiles-Shields Colleen , Cummings Caroline , Montague Enid , Plevinsky Jill M. , Psihogios Alexandra M. , Williams Kofoworola D. A.
Published: April 2022

Mental health disparities directly tie to structural racism. Digital mental health (DMH), the use of technologies to deliver services, have been touted as a way to expand access to care and reduce disparities. However, many DMH fail to mitigate the persistent disparities associated with structural racism that impact delivery (e.g., costs, dependable internet access)–and may even exacerbate them. Human-centered design (HCD) may be uniquely poised to design and test interventions alongside, rather than “for,” marginalized individuals. In employing HCD methodologies, developers may proceed with a vested interest in understanding and establishing empathy with users and their needs, behaviors, environments, and constraints. As such, HCD used to mindfully address structural racism in behavioral health care may address shortcomings of prior interventions that have neglected to elevate the voices of marginalized individuals. We argue that a paradigm shift in behavioral health services research is critically needed–one that embraces HCD as a key methodological framework for developing and evaluating interventions with marginalized communities, to ultimately promote more accessible, useful, and equitable care. The current commentary illustrates practical examples of the use of HCD methodologies to develop and evaluate DMH designed with marginalized populations, while also highlighting its limitations and need for even greater inclusivity. Following this, calls to action to learn from and improve upon HCD methodologies will be detailed. Acknowledging potential limitations of current design practices, methodologies must ultimately engage representative voices beyond research participation and invest in their active role as compensated and true collaborators to intervention design.
Application of Deep Learning in Land Use Classification for Soil Erosion Using Remote Sensing
Authors: Wan Lihong , Li Shihua , Chen Yao , He Ze , Shi Yanli
Published: April 2022

China is suffering from serious soil and water loss due to improper land use, leading to flood and drought disasters, and industrial and agricultural reduction. The commonly used monitoring methods of soil and water loss rely on the visual interpretation of remote sensing images, which is time-consuming and laborious. In this study, deep learning semantic segmentation technology was applied to monitoring land use for soil and water conservation. Manual visual interpretation mark samples and land use products collected in recent years were combined to construct training samples for deep learning. Deep convolution neural network model based on ResNet152 and DeeplabV3+ was selected for performing land use classification. Then the soil and water loss were quantified using the Chinese Soil Loss Equation (CSLE) based on the hydrological, geographic, vegetation cover and land use information. The experimental results show that the deep learning model can quickly extract robust edge features from remote sensing images and has high pixel accuracy (83.4%). Although the model accuracy was affected by the land cover types and image quality in different study area, it can still achieve an accuracy higher than 70% in other counties through our experiment. It can further improve the information service level of soil and water conservation product, and provide a useful guideline for automatic land use interpretation and identification of soil and water conservation status based on high resolution remote sensing images.
Response and Potential Indication to Hypoxia in the Changjiang River Estuary and its Adjacent Waters: Insight From Redox-Sensitive Trace Elements in Sediment Core
Authors: Zhang Xiaotong , Yuan Huamao , Song Jinming , Duan Liqin
Published: April 2022

The migration and enrichment of redox-sensitive trace elements (RSEs) from seawater to sediments are controlled not only by their geochemical properties but also by marine redox conditions. Therefore, RSEs, such as Mo, U, and V, are extensively used to indicate redox states in marine environments. To retrieve the historical redox state in the hypoxic zone near the Changjiang River Estuary and its adjacent waters, the distribution and enrichment degree of Mo, U, and V in a sediment core collected from the recurrently hypoxic region were investigated. The correlation analysis shows that the authigenic enrichment of Mo and U in sediment core 3,050–2 is primarily controlled by redox conditions, rather than sediment grain size, adsorption on organic matters, Fe–Mn (hydr)oxides, and terrigenous detritus input. Mo-U covariation is selected to analyze the evolution of redox conditions in the seasonally hypoxic zone. The MoEF/UEF values in this sediment core are almost between 0.1 and 0.3×Mo/Umodern seawater value and show a general decreasing trend with depth, indicating an overall progressive transition from oxic to suboxic conditions in this area since 2005. The close MoEF/UEF values and similar chronological Mo-U variations by comparing our results with previous studies in adjacent areas offer common evidence for the gradually intensified bottom water–oxygen stress, suggesting the possible application of MoEF/UEF in retrieving redox development in this coastal hypoxic zone.
Study on the Influence of Rock Clip Production and Empty Hole Volume Effect of Upward Blind Shaft Blasting
Authors: Huang Yonghui , Sun Bo , Zhang Zhiyu , Meng Jiale , Zeng Hua
Published: April 2022

Cutting blasting is the principal construction method for roadway and shaft excavation, but the studies on the damage mechanism of cutting blasting affected by the volume effect of empty holes under high ground stress are not insufficient. During cutting blasting, different damage zones are formed. In this paper, combined with the rock damage criterion and RHT constitutive function, the ranges of these damage zones are determined. The smooth particle hydrodynamics method is used to study the influence of high in-situ stress on rock blasting damage from the perspective of the number of empty holes and the production coefficient of rock clamp. The accuracy of the determined damage zone range is verified by supplemented field tests. The research results show that in the process of rock clamp production, the propagation of blasting stress wave is inhibited, especially the tensile stress wave which is more obviously inhibited. The empty holes reduce the inhibitory effect of rock clamp production. With the increase in the production coefficient of rock clip, the blasting damage radius is reduced by 39.7%, 35.1%, 30.5%, 26.7%, and 22.9% compared with the theoretical value, respectively, while its influence on the radius of crushing zone is small. The three-dimensional scanning results were used to inverse calculate the production coefficient of the rock clip. The fitting degree between the numerical simulation and the field test scanning results is about 94.5%, which proves the accuracy of the RHT constitutive parameters and the reliability of the determination range. The mathematical relationship between the production coefficient Kr for rock clip and the relative height H of the wellhead and the area Sc of the cross-section cavity is fitted based on the data of several upward cutting blasting field tests.
Ab Initio Molecular–Dynamics Study of Structural and Bonding Properties of Liquid Fe–Light–Element–O Systems Under High Pressure
Authors: Ohmura Satoshi , Shimojo Fuyuki , Tsuchiya Taku
Published: April 2022

The structural and bonding properties of liquid iron–light–element–oxygen ternary systems such as Fe–H–O, Fe–C–O, Fe–Si–O, and Fe–S–O under high pressure are studied by ab initio molecular dynamics simulations. H, C, O, Si, and S are the candidate light elements in the Earth’s outer core (liquid iron is a major constituent). From our simulations, it is found that H, C, and O show “interstitial” type behavior while Si and S show “substitutional” type behavior in the liquid iron–light–element–O ternary systems. For the interactions between light elements, C–C, Si–Si, and Si–O show covalent–like interactions even under high–pressure condition. The Si–O covalent bond causes a shift in the ionic charge of Si to more positive, which could be related to the immiscibility of liquid Fe–Si–O.
Plant Consumption by Early-Middle Neolithic Peoples in Guangxi, South China: Archaeobotanical Evidence From the Dingsishan Site
Authors: Zhang Xi , Huang Chao , Zhou Zhenyu , Olsen John W. , Huang Qiang , Guan Ying
Published: April 2022

The Dingsishan Site, located in Nanning City, Guangxi Zhuang Autonomous Region, is one of the most important Neolithic archaeological sites in the Lingnan region of China’s southeastern seaboard. Plant microfossil remains recovered from excavated artifacts and human teeth suggest that the site’s ancient inhabitants practiced a subsistence system based on foraging. Wild plant food resources dominated their vegetal diet. Starch granules extracted from residue samples represent various taxa, including plant roots and tubers, aquatic plant fruits, beans, and wild cereals, defining the primary vegetal diet of Dingsishan’s Neolithic occupants. In addition, residue samples from shell artifacts yielded starch granules and phytolith remains, providing significant clues as to the function of these tools. We also identified millet starch granules from Dingsishan Cultural Phases 3-4 (ca. 7,000–6000 BP), albeit in extremely low quantities. Holocene paleoecological conditions in the Lingnan area provided diverse and plentiful wild food resources, allowing the relatively late emergence of agriculture. Our study suggests that Middle Neolithic human groups in the Yong River drainage consumed various plants, and their subsistence pattern was relatively stable through the four Cultural Phases identified at Dingsishan. Our conclusions enhance understanding the diversity of plant food resources exploited by foraging societies and interpretations of differences in patterns of agricultural origins in different ecological regions of China.
Mathematical Epistemic Beliefs: Through the Gender Lens
Authors: Trakulphadetkrai Natthapoj Vincent
Published: April 2022

This large survey study set out to ascertain whether gender differences in teachers’ mathematical epistemic beliefs exist, and the extent to which teachers’ gender as well as their teaching experience level, education level, and socio-economic setting of the schools can predict these beliefs. Specifically, the study examined teachers’ beliefs concerning the structure, stability, and source of mathematical knowledge. This is crucial given that previous research have demonstrated the potential role of teachers’ mathematical epistemic beliefs in shaping their mathematics teaching, and hence their students’ mathematics learning outcomes and perceptions of the subject. The current study drew on survey data collected from 745 primary teachers using items from the Thai Teachers’ Mathematics Education-related Beliefs (TTMEB) questionnaire. The data were analysed using Independent-samples t-test and multiple regression. The findings reveal a very limited to no effect of gender on teachers’ mathematical epistemic beliefs, and also alert us to the fact that when it comes to exploring factors that shape one’s beliefs, their exogenous characteristics, such as the socio-economic setting of where they live and work, should too be taken into account. Overall, the study helps to dispel any myths about gender differences in the way male and female teachers perceive mathematics, specifically the nature of mathematical knowledge.
Mediterranean Diet: What Are the Consequences for Menopause?
Authors: Vetrani Claudia , Barrea Luigi , Rispoli Rosa , Verde Ludovica , De Alteriis Giulia , Docimo Annamaria , Auriemma Renata Simona , Colao Annamaria , Savastano Silvia , Muscogiuri Giovanna
Published: April 2022

Menopause is a natural event occurring in a woman’s life that is often accompanied by symptoms that might affect the quality of life. Diet has been shown to influence menopausal-related symptoms. Therefore, the present study aimed to investigate whether the adherence to the Mediterranean Diet (MD) might influence menopausal symptoms in women with obesity. This cross-sectional study involved postmenopausal women with obesity. Anthropometric and clinical parameters, and lifestyle habits were evaluated. All participants underwent interview questionnaires to assess: the adherence to the MD (PREDI PREvencion con DIetaMEDiterranea, PREDIMED), sleep quality (Pittsburgh Sleep Quality Index, PSQI), and severity of menopausal symptoms (Menopausal Rating Scale, MRS). One hundred postmenopausal women were enrolled (age 57.1 ± 7.3 years, BMI 35.0 ± 5.5 kg/m2). The mean PREDIMED score was 7.82 ± 1.66 showing moderate adherence to MD. Women in the marked MRS class had a significantly lower PREDIMED score than the none-to-moderate MRS class (p=0.036). The intake of legumes was associated with a lower MRS class (r= -0.201, p=0.045). In addition, the intake of extra-virgin olive oil inversely correlated with psychological symptoms (r= -0.230 p=0.021). Finally, 79% of participants were poor sleepers (mean PSQI score was 8.68 ± 3.6) and women in the severe MRS class had a worse sleep quality compared to other MRS classes. Post-menopausal women with marked menopausal symptoms had low adherence to MD. Legume consumption was associated with lower menopausal symptoms severity while extra virgin olive oil consumption was associated with lower psychological symptoms.
Metal-Supported Solid Oxide Electrolysis Cell Test Standard Operating Procedure
Authors: Shen Fengyu , Welander Martha M. , Tucker Michael C.
Published: April 2022

This procedure describes the setup and testing protocol for metal-supported solid oxide electrolysis cell (MS-SOEC) button cell performance evaluation. It defines a standard testing protocol, describes materials selection, and identifies common pitfalls for testing MS-SOEC button cells.
Evaluation of Long-Term Modeling Fine Particulate Matter and Ozone in China During 2013–2019
Authors: Mao Jianjiong , Li Lin , Li Jingyi , Sulaymon Ishaq Dimeji , Xiong Kaili , Wang Kang , Zhu Jianlan , Chen Ganyu , Ye Fei , Zhang Na , Qin Yang , Qin Momei , Hu Jianlin
Published: April 2022

Air quality in China has been undergoing significant changes due to the implementation of extensive emission control measures since 2013. Many observational and modeling studies investigated the formation mechanisms of fine particulate matter (PM2.5) and ozone (O3) pollution in the major regions of China. To improve understanding of the driving forces for the changes in PM2.5 and O3 in China, a nationwide air quality modeling study was conducted from 2013 to 2019 using the Weather Research and Forecasting/Community Multiscale Air Quality (WRF/CMAQ) modeling system. In this study, the model predictions were evaluated using the observation data for the key pollutants including O3, sulfur dioxide (SO2), nitrogen dioxide (NO2), and PM2.5 and its major components. The evaluation mainly focused on five major regions, that is , the North China Plain (NCP), the Yangtze River Delta (YRD), the Pearl River Delta (PRD), the Chengyu Basin (CY), and the Fenwei Plain (FW). The CMAQ model successfully reproduced the air pollutants in all the regions with model performance indices meeting the suggested benchmarks. However, over-prediction of PM2.5 was noted in CY. NO2, O3, and PM2.5 were well simulated in the north compared to the south. Nitrate (NO3−) and ammonium (NH4+) were the most important PM2.5 components in heavily polluted regions. For the performance on different pollution levels, the model generally over-predicted the clean days but underpredicted the polluted days. O3 was found increasing each year, while other pollutants gradually reduced during 2013–2019 across the five regions. In all of the regions except PRD (all seasons) and YRD (spring and summer), the correlations between PM2.5 and O3 were negative during all four seasons. Low-to-medium correlations were noted between the simulated PM2.5 and NO2, while strong and positive correlations were established between PM2.5 and SO2 during all four seasons across the five regions. This study validates the ability of the CMAQ model in simulating air pollution in China over a long period and provides insights for designing effective emission control strategies across China.