bluuebunny/crossref_metadata_2025 huggingface dataset:
INSIGHTS FROM A MONOSPECIFIC LINGULID BRACHIOPOD BED IN THE LATE DEVONIAN OF SOUTH AFRICA
Authors: HARRIS CHRISTOPHER , GESS ROBERT W.
Published: September 2022

A formerly unknown fossil-bearing locality in the lower part of the Witpoort Formation (Witteberg Group, Cape Supergroup) is described from the Eastern Cape (South Africa). Uniquely for these strata, it provides evidence for a back-barrier lagoon hosting a monospecific lingulid brachiopod fauna. This represents the youngest record of marine invertebrates within the Cape Supergroup. The occurrence extends the age range of the genus Dignomia Hall into the Famennian Stage, contrary to previous estimates of an Ordovician to mid-Devonian range. Abundant lingulid brachiopod valves are associated with plant and fish remains within a laterally extensive, up to nine-meter-thick mudstone. Shell compressions are concentrated in patches within the upper portion of the horizon and are preserved parallel to bedding as well as perpendicular and oblique to bedding (apparently in situ). Plant fossils exhibit a greater degree of transport than in other studied Witpoort Formation mudrock layers (Coombs Hill and Waterloo Farm). The monospecifity of the shelly invertebrate fauna derives from environmental stress and lingulid brachiopods' unusual ability to tolerate fluctuating environmental conditions, including salinity, oxygen levels, and temperature. Ichnofauna within the deposit include, among others, Nereites and ‘Spirophyton', suggesting opportunistic colonization of the substrate by deposit feeding invertebrates in a marine-dominated backshore setting. The Late Devonian was a time of global environmental disequilibrium, characterized by periodic flooding of continental margins and massive biotic overturn. Ongoing research into eustatic and environmental changes recorded within the Witpoort Formation uniquely provide insights into high latitude conditions during the Famennian.
BIOSIGNATURE PRESERVATION AIDED BY ORGANIC-CATION INTERACTIONS IN PROTEROZOIC TIDAL ENVIRONMENTS
Authors: MOORE KELSEY R. , PRESENT THEODORE M. , PAVIA FRANK , GROTZINGER JOHN P. , HOLLIS JOSEPH RAZZELL , SHARMA SUNANDA , FLANNERY DAVID , BOSAK TANJA , TUITE MICHAEL , KNOLL ANDREW H. , WILLIFORD KENNETH
Published: September 2022

The preservation of organic biosignatures during the Proterozoic Eon required specific taphonomic windows that could entomb organic matter to preserve amorphous kerogen and even microbial body fossils before they could be extensively degraded. Some of the best examples of such preservation are found in early diagenetic chert that formed in peritidal environments. This chert contains discrete domains of amorphous kerogen and sometimes kerogenous microbial mat structures and microbial body fossils. Our understanding of how these exquisite microfossils were preserved and the balance between organic degradation and mineral formation has remained incomplete. Here, we present new insights into organic preservation in Proterozoic peritidal environments facilitated through interactions among organic matter, cations, and silica. Organic matter from Proterozoic peritidal environments is not preserved by micro- or cryptocrystalline quartz alone. Rather, preservation includes cation-rich nanoscopic phases containing magnesium, calcium, silica, and aluminum that pre-date chert emplacement and may provide nucleation sites for silica deposition and enable further chert development. Using scanning electron microscopy and elemental mapping with energy dispersive X-ray spectroscopy, we identify cation enrichment in Proterozoic organic matter and cation-rich nanoscopic phases that pre-date chert. We pair these analyses with precipitation experiments to investigate the role of cations in the precipitation of silica from seawater. Our findings suggest that organic preservation in peritidal environments required rapid formation of nanoscopic mineral phases through the interactions of organic matter with seawater. These organic-cation interactions likely laid the initial foundation for the preservation and entombment of biosignatures, paving the way for the development of the fossiliferous chert that now contains these biosignatures and preserves a record of Proterozoic life.
Age and gender difference in blood pressure associations with cardiovascular outcomes and diabetes: a national population-based cohort study
Authors: yu qi , Jin Qing-Dong
Published: September 2022

Objective We aim to analyze the age and gender difference in blood pressure(BP) associations with cardiovascular outcomes and diabetes in middle aged and elderly Chinese population. Method We included a total of 4,405 adults aged 40–80 years from the China Health and Nutrition Survey (CHNS) cohort. Cox proportional hazards regression models were used to estimate hazard ratios and 95% CIs. Restricted cubic spline analyses were used to explore linear and nonlinear relationships of BP with disease risk. Result With a mean follow-up of 12.2 years, 627 individuals progressed to at least one condition. Multivariable adjusted Cox models showed a strong positive association between BP and cardiovascular outcomes. Each 10 mm Hg higher usual systolic BP was significantly associated with myocardial infarction(MI)(HR[95%CI]: 1.16[1.07–1.27]), stroke(HR[95%CI]: 1.31[1.23–1.40]), and diabetes(HR[95%CI]: 1.1[1.03–1.17]). In subgroup analysis, BP was strongly associated with cardiovascular outcomes in young age group and associated with diabetes in female individuals. Conclusion BP was more strongly associated with stroke than with MI and diabetes. The strength of these associations declined with increasing age. Besides, either systolic BP or diastolic BP was more strongly associated with diabetes in female individuals than male individuals.
Submassive Pulmonary Embolism in the Setting of Intracerebal Hemorrhage: A case report on suction thrombectomy
Authors: Ciurylo William
Published: September 2022

Pulmonary embolism (PE) in the setting of intracerebral hemorrhage (ICH) is an unfortunate, challenging, and highly morbid clinical problem. Interventional strategies have lower associated bleeding risks than the standby for PE treatment: systemic anticoagulation. Despite this benefit, there are few examples in the literature of its utilization in the management of PE in the setting of ICH. This present case provides an example of the successful utilization of suction thrombectomy to manage a PE in the setting of ICH.
An 80-year-old female presented to an outside hospital with complaints of dizziness, headache, nausea, and vomiting of abrupt onset one hour prior to arrival. Computed tomography (CT) of the head with CT Angiography (CTA) of the head and neck was performed and demonstrated hemorrhage in all ventricles; most prominently within the left lateral ventricle. Magnetic Resonance Imaging (MRI) of the brain suggested that the cause of her hemorrhage was reperfusion injury after a small acute infarction in the left internal capsule in the setting of anticoagulant use. Ten days after her diagnosis of ICH, a submassive PE was diagnosed with a class IV Pulmonary Embolism Severity Index. An interdisciplinary evaluation was conducted between hospitalist medicine, neurology, neurosurgery, and interventional radiology. Successful suction thrombectomy was performed on hospital day 11. No new neurologic deficits were appreciated post-procedure. Patient’s heartrates remained elevated by improved. Blood pressures remained controlled. Patient was weaned off oxygen to room air. Neurosurgery assessed patient to be of acceptable risk for discharge with further deferment of anticoagulation until repeat CT Head six weeks after discharge. Patient was discharged on hospital day 14.
Treating PE in the setting of ICH is without clear guidelines. The appropriate treatment modality is reliant upon the clinical judgement and the individual details of each case. In this case, a high Pulmonary Embolism Severity Index with imaging demonstrating a stable hematoma without evidence of new blood resulted in the decision to use a suction thrombectomy. More research is needed to develop consistent evidence-based guidelines for this clinical challenge.
PGMG: A Pharmacophore-Guided Deep Learning Approach for Bioactive Molecular Generation
Authors: Li Min , Zhu Huimin , Zhou Renyi , Tang Jing
Published: September 2022

The rational design of novel molecules with desired bioactivity is a critical but challenging task in drug discovery, especially when treating a novel target family or understudied targets. Here, we propose PGMG, a pharmacophore-guided deep learning approach for bioactivate molecule generation. Through the guidance of pharmacophore, PGMG provides a flexible strategy to generate bioactive molecules matching given pharmacophore models. PGMG uses a graph neural network to encode pharmacophore features and spatial information and a transformer decoder to generate molecules. A latent variable is introduced to solve the many-to-many mapping between pharmacophores and molecules and improve the diversity of generated molecules. In addition, these generated molecules are of high validity, uniqueness, and novelty. In the case studies, we demonstrate using PGMG in ligand-based and structure-based drug de novo design, as well as in lead optimization scenarios. Overall, the flexibility and effectiveness make PGMG a useful tool to accelerate drug discovery process.
Protective effects of pentoxifylline against chlorine-induced acute lung injury in rats
Authors: Liu Meng-meng , Liu Jiang-zheng , Zhao Chen-qian , Guo Peng , Wang Zhao , Wu Hao , Yu Wei-hua , Liu Rui , Hai Chun-xu , Zhang Xiao-di
Published: September 2022

Objective
Chlorine is a chemical threat agent that can be harmful to humans. Inhalation of high levels of chlorine can lead to acute lung injury (ALI). Currently, there is no satisfactory treatment, therefore, effective antidote is urgently needed. Pentoxifylline (PTX), a methylxanthine derivative and nonspecific phosphodiesterase inhibitor, is widely used for the treatment of vascular disorders. The present study aimed to investigate the inhibitory effects of PTX on chlorine-induced ALI in rats.
Methods
Rats were exposed to chlorine. The histopathological examination were carried out. The effect of administration of PTX was evaluated. The expression of oxidative stress, hypoxia, and autophagy markers were examined by western blotting assay.
Results
The histopathological examination demonstrated that chlorine could destroy the lung structure with hemorrhage, alveolar collapse, and inflammatory infiltration. ROS accumulation was significantly higher in the lung of rats suffering from inhaling chlorine. The results also showed that PTX markedly alleviated the expression of lactate dehydrogenase (LDH), oxidative stress, and hypoxia. Additionally, PTX up-regulated the level of autophagy.
Conclusion
PTX could ameliorate chlorine-induced lung injury, thus suggesting that PTX could serve as a potential therapeutic approach for ALI.
The Impact of Firm-Level Innovation on Labor Productivity and Employment in Selected African Countries
Authors: Eshete Zerayehu Sime , Gebreyohanes Getaw Tadesse
Published: September 2022

The overriding objective of this study is to examine the impact of different types of innovations (overall, process, and R&D) on different segments of labour (productivity and employment) in selected African countries, namely, Ethiopia, Kenya, Rwanda, Zambia, Zimbabwe, Ghana, Cameroon, Senegal, and Cote d'Ivoire. The study employs data from the World Bank Enterprise Survey and converts it into pseudo panel data based on legal status, firm size, and industry type as all these three exogenous variables are common in all countries. The study uses the Propensity Score Matching method and the Dose-Response Model to capture the impact of innovation and the dosage of innovation on labour productivity and employment. The descriptive analysis indicates that 2,673 firms are engaged in at least one of the innovation activities, and 250 firms do not have any innovation activities. The Propensity Score Matching finds that process and R&D innovations have statistically significant impacts on employment. But the process of innovation has a negative effect on the productivity of non-production and skilled employees. R&D innovation has a negative and statistically significant impact on the productivity of permanent, non-production, skilled, and unskilled workers. In addition to these, the Dose-Response-Model exhibits the positive relationship between innovation and employment of full-time permanent employees, full-time production, and full-time nonproduction workers, and the impact becomes greater when the dose increases. However, there is a negative relationship between innovation and employment of unskilled production workers, after which their relationship becomes positive.

Classification code JEL: O31, O32
A systematic review on trade-off analysis in agriculture
Authors: Breure Timo , Estrada-Carmona Natalia , Petsakos Athanasios , Gotor E. , Jansen B. , Groot Jeroen
Published: September 2022

Achieving multiple sustainable development goals simultaneously demands managing agricultural resources for different objectives and actively considering how these objectives compete (trade-offs) or complement (synergies). Trade-off analyses (TOA) are therefore central for policy and decision-making to achieve sustainable agricultural landscapes. Yet, evidence on TOA assessments in agriculture remains scattered due to the wide scope of research disciplines and objectives for which TOA is applied. We conducted a systematic review on 119 peer-reviewed articles to identify how TOAs are implemented within the agricultural context and what associated knowledge gaps exist. Our results highlight limited use of objectives that capture environmental and socioeconomic services from agriculture. Likewise, TOAs that consider effects or impacts across multiple spatial scales are an exception. Overall, our assessment identified that current TOA frameworks rarely include stakeholders in the co-development of the study, disregard TOA recommendations’ uncertainty due to outcome variability and overlook risks associated with the TOA outcomes. Increased attention to these aspects is critical for conducting TOAs that guide agricultural landscapes towards sustainability.
Cerebrospinal fluid lipoproteins inhibit α-synuclein aggregation by interacting with oligomeric species in seed amplification assays
Authors: Bellomo Giovanni , Paciotti Silvia , Concha-Marambio Luis , Rizzo Domenico , Gatticchi Leonardo , Cerofolini Linda , GIuntini Stefano , De Luca Chiara Maria Giulia , Ma Yihua , Farris Carly M. , Pieraccini Giuseppe , Bologna Sara , Filidei Marta , Ravera Enrico , Lelli Moreno , Moda Fabio , Fragai Marco , Parnetti Lucilla , Luchinat Claudio
Published: September 2022

Background: Aggregation of α-synuclein (α-syn) is a prominent feature of Parkinson’s disease (PD) and other synucleinopathies. In these diseases, the extracellular spreading of misfolded α-syn significantly contributes to the cell-to-cell propagation of the α-syn misfolding pathology in a prion-like fashion. Therefore, extracellular α-syn aggregates are considered primary targets both for diagnostics and for novel disease modifying therapies. Currently, α-syn seed amplification assays (SAAs) using cerebrospinal fluid (CSF) represent the most promising diagnostic tools for synucleinopathies. However, CSF itself contains several compounds that can modulate the aggregation of α-syn in a patient-dependent manner, potentially sabotaging unoptimized α-syn SAAs and preventing seed quantification.
Methods: In this study, we characterized the inhibitory effect of CSF on in vitro α-syn aggregation by means of CSF fractionation, mass spectrometry, dot-blot, Western blot, transmission electron microscopy, solution nuclear magnetic resonance spectroscopy, a highly accurate and standardized diagnostic SAA, and different in vitro aggregation conditions to evaluate spontaneous aggregation of α-syn.
Results: We found the high-molecular weight fraction of CSF (>100,000 Da) to be highly inhibitory and identified lipoproteins to be the main drivers of this effect. We evaluated direct interaction between lipoprotein and α-syn and observed lipoprotein-α-syn complexes by transmission electron microscopy. Direct interaction between lipoproteins and monomeric α-syn was not detected by solution nuclear magnetic resonance spectroscopy, suggesting interaction between lipoproteins and oligomeric/proto-fibrillary α-syn intermediates instead. Lastly, we observed significantly slower amplification of α-syn seeds in PD CSF when lipoproteins were added to the reaction mix of a highly accurate diagnostic SAA.
Conclusions: Our results describe a novel interaction between lipoproteins and α-syn aggregates that inhibits the formation of α-syn fibrils and could have relevant biological and translational implications. Indeed, the donor-specific inhibition of CSF on α-syn aggregation explains the lack of quantitative results so far obtained by the analysis of SAA-derived kinetic parameters. Furthermore, our data show that apolipoproteins are the main inhibitory components of CSF, suggesting that lipoprotein concentration measurements could be incorporated into data analysis models to eliminate the confounding effects of CSF milieu on α-syn quantification efforts.
Assessments of physico-chemical parameters, nutrient load and trace metal levels in spring and river water using multivariate statistical methods, South Gondar Zone, Ethiopia
Authors: Kassaw Marye Mulugeta , Meke Maru , Tibebe Dessie , Kokeb Addis , Moges Zerubabel , Yenealem Dereje , Legesse Mulugeta , Gashaw Tamiru
Published: September 2022

Physico-chemical and selected heavy metals were investigated. Seven water samples were collected. The results of water quality parameters ranged pH, EC, TSS, turbidity, TDS, total alkalinity, DO, temperature, Salinity, Chlorides, NH3, PO4 − 3, SO4 − 2, NO3 − 2, NO2− 0.015 to 0.139 mg/L, Cr, Mn, Fe, Ni, Pb and Cd. Most of the results are comparable with WHO standards, in contrast some of are above permissible limits. Evaluated data through multivariate statistical techniques Principal correlation analysis (PCA), Cluster analysis and correlation matrix were performed. The sampling points extracted three clusters for nutrient water quality which suggested similar pollution sources. The water sample was polluted due to the anthropogenic effects of Mekan Eyesus Town while in the spring water high concentrations of Cl−, NH3 and PO4 − 3 were recorded. These might be natural sources of pollution. Most of the physicochemical parameters and the nutrients showed significant relationships except for TSS with all other parameters.
Sedimentary structures of microbial carbonates in the fourth member of the Middle Triassic Leikoupo Formation, western Sichuan Basin, China
Authors: Wang Yuanchong , Shi Kaibo , Liu Bo
Published: September 2022

In recent years, abundant natural gas have been found in microbial carbonates in the fourth member of the Leikoupo Formation in western Sichuan Basin. In this study, from the observation of 626 microbial thin sections, four types of microbial carbonates are classified based on the differences of meso-structures. Among them, thrombolites and stromatolites are subdivided into eight types based on the differences of micro-structures. Six types of microbial micro-structure association (MSA) are identified, and are mainly developed in microbial mounds. The energy of sedimentary environment and hydrodynamic conditions of them from low to high is MSA-5, MSA-1, MSA-6, MSA-3, MSA-4 and MSA-2. Because of the arid climate in the Annie Period, a restricted platform are developed in T2l43 in western Sichuan Basin, and the sedimentary faces are lagoon (gypsiferous lagoon or salt lake in evaporate conditions), microbial mounds, shoals, inner platform shoals and open sea from the east to the west. Microbial micro-structure not only affects the pore evolution of microbial carbonate reservoirs, but also affects the diagenesis of microbial carbonate reservoirs of the Lei-4.
Determination of Electromagnetic properties of Concrete Using Microwave Non-Destructive testing techniques and Artificial neural networks
Authors: Guntamukkala Madhuri , Gonthina Madhuri , Lute Venkat , Mathur Parul , Kurup Dhanesh G
Published: September 2022

Every year, a massive amount of literature is published on many aspects of microwave applications. Over the past few years, the need for progressive methods for assessing different properties of concrete, as well as for maintenance and monitoring of structures, has led to the development of microwave non-destructive testing (MNDT) techniques for preserving the civil infrastructure. As the number of studies being published in this field is growing fast, it is important to categorize the studies at deeper levels. In this paper, a concrete cube of M20 grade has been created in ANSYS HFSS for simulation purposes. An artificial rectangular crack was developed in the concrete cube and the simulation was run at dielectric constants from 1–10 with 0.5 intervals, loss tangents from 0.001,0.1 &0.2, and the gap between sample and circular waveguide from 0-7cm with 1cm interval. The artificial neural network was developed in python for Mean square Error(MSE) analysis and prediction of Electromagnetic properties(Dielectric constant and Loss tangent) with inputs as the S-parameter(real and imaginary) data of the Homogenous sample and sample with Rectangular crack. The result analysis shows the variation in Mean squared error for crack and No-crack concrete samples.
Anlotinib Dramatically Improved Pulmonary Hypertension and Hypoxia Caused by Pulmonary Tumor Thrombotic Microangiopathy (PTTM) Associated with Gastric Carcinoma: A Case Report
Authors: Wang Yang , Ning Wei-wei , Jin Yi-fan , Zhu Qing-qing , Wang Zai-liang , Su Nan , Chen Yan-bin , Huang Jian-an , Chen Cheng
Published: September 2022

Background: Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare malignancy-related respiratory complication, demonstrating rapid progression of pulmonary hypertension (PH) and respiratory failure. Although a number of treatments have been attempted for patients diagnosed with or suspected of having PTTM, successful-treated cases of PTTM were mainly from imatinib therapy, which was a PDGF receptor inhibitor. Anlotinib was a novel tyrosine kinase inhibitor that targets VEGFR, FGFR, PDGFR, and c-kit.
Case presentation: We reported a case of PTTM associated with gastric carcinoma, whom were treated with anlotinib, thereby exhibiting significant improvement of PH and respiratory dysfunction.
Conclusion: Our case provides a new understanding of therapy to PTTM, with implications for defining anlotinib as candidate drug for PTTM. Clinical diagnosis and prompt initiation of anlotinib might be one of the strategies in patients with unstable PTTM.
Dietary supplementation of termitarium soil ameliorated the gut microbiota in captive Chinese pangolins
Authors: Zhang Zhidong , Wang Kai , An Fuyu , Xu Xuelin , Yan Hongmei , Kuang Yingjie , Zou Chuanshan , Hua Yan
Published: September 2022

Background: Chinese pangolin (Manis pentadactyla), one of the most endangered species in the world, has suffered a sharp decline due to heavy hunting and illegal trade. The artificial diet has difficulty satisfying the nutritional needs of captive pangolins, and it has become one of the main factors limiting the development of ex-situ conservation of pangolins. Gastrointestinal diseases are one of the most common diseases affecting the survival of captive Chinese pangolins and arecaused by an imbalance in gut microbiota. In the wild, the pangolin is a highly specialized species with a diet dominated by ants and termites and an intake ofsome termitarium soil. However, the effects of supplementation with termitarium soil on the gut microbiota of captive Chinese pangolins are poorly understood.
Results: Using 16S rRNA sequencing technology, the gut microbiota of the control group (CZ), the sterilized termitarium soil group (MZ), and the unsterilized termitarium soil group (BZ) were compared. These results showed that there was no significant difference in alpha diversity, while the results of unweighted UniFrac PCoA showed obvious separation among the three groups. At the phylum level, Firmicutes, Proteobacteria, and Bacteroidetes were the main bacterial phyla. The relative abundance of Bacteroidetes was decreased in the BZ group compared to the CZ group. Clostridium_sensu_stricto_1, Streptococcus, Cellulosilyticum, and Escherichia_Shigella were the main bacterial genera at the genus level. Unsterilized termitarium soilincreased the relative abundances of Cellulosilyticum, Bacillus, and Clostridium_sensu_stricto_13 and decreased the relative abundances of Bacteroides, Clostridiales_unclassified, Ruminococcus]_gnavus_group, and Veillonella. The Lefse results showed that Cellulosilyticum, Clostridium_sensu_stricto_13, and Bacillus were enriched in the BZ group. The concentrations of acetic acid, propionic acid, and butyric acid were decreased in the BZ and MZ groups.
Conclusions: These results indicated that dietary supplementation with termitarium soil did not alterthe richness of the gut microbiota, but reduced proinflammatory-related bacteria and increased intestinal absorption-related bacteria, which improves the efficiency of SCFA absorption. Collectively, this study provides a potential method for ameliorating the intestinal homeostasis of captive Chinese pangolins.
Single-crystal X-ray diffraction and IR-spectroscopy studies of K-deficient fluorapophyllite
Authors: Seryotkin Yurii V. , Kupriyanov Igor N. , Ignatov Mark A.
Published: September 2022

Three samples of fluorapophyllite with different cation composition were studied by the X-ray diffraction and IR-spectroscopy methods. The samples (K0.72(NH4)0.20)Σ0.82Na0.08 Ca4[Al0.04Si7.96O20]F·8H2O from Nidym and K0.87Na0.06 Ca4[Si8O20]F·8H2O from Akhaltsykhe localities are characterized by the deficiency of large cations K+ and (NH4)+ in the M site; the chemical composition of Talnakh sample (K0.94(NH4)0.06)Σ1.00 Ca4[Si8O20]F·8H2O is close to the stoichiometric one. The large cations deficiency in the structure of Nidym and Akhaltsykhe samples is compensated by the presence of medium-sized Na+ cations, located 1.12–1.31 Å away from the M position. The planar coordination of Na is formed by four H2O molecules. The occurrence of ammonium ions is found for the Nidym and Talnakh fluorapophyllites and their concentrations are estimated from the IR spectra and structure refinement. Polarized infrared measurements performed for apophyllite samples oriented along the c-axis reveal pleochroic behavior of the OH absorption bands. The observed pleochroism is explained in terms of absorption from two OH vectors of the H2O molecules in the apophyllite crystal structure.
Effects of the Covid-19 Pandemic on Gestational Diabetes in Castilla La Mancha (Spain)
Authors: Calderón Dulce María , Marco Amparo , Gómez Inés , Quílez Rosa , Quiroga Iván , Delgado Manuel , Gargallo Javier , Olmos María , Miralles Raquel , Gonzalvo César , González Javier
Published: September 2022

Aim: To assess the effect of the coronavirus disease 2019 (COVID-19) pandemic on gestational diabetes mellitus (GDM).
Methods: In this observational, multicentre, retrospective study conducted in Castilla La Mancha, Spain, we compared 663 women with GDM exposed to pandemic (pandemic group) with 622 women with GDM who were attended 1 year before (prepandemic group). The primary outcome was large for gestational age (LGA) newborns as an indicator of GDM poor control. Secondary outcomes included maternal and neonatal morbidity.
Results: During the pandemic the gestational week at diagnosis (24.2 ± 7.4 vs 22.9 ± 7.7, p = 0.0016) and at the first visit to Endocrinology (26.6 ± 7.2 vs 25.3 ± 7.6, p = 0.0014) were earlier. Face-to-face visits were maintained to a large extent (80.3%). The new diagnostic criteria of GDM was only used in the 3% of cases. However, in the pandemic group the final HbA1c was higher (+ 0.09%, p = 0.047) and there were more LGA newborns (8.5% vs 12.8%, p = 0.015). There were no differences in perinatal complications.
Conclusion: Medical care for GDM in our Public Health System did not suffer a significant deterioration during the pandemic. However, this did not prevent a greater number of LGA newborns. The use of temporary alternatives for the diagnosis of GDM during the Covid-19 pandemic was associated with having a LGA newborn. These diagnostic criteria should be reconsidered or maybe in future pandemics we should maintain the usual diagnostic protocol.
Neuroblastoma response to RAS-MAPK inhibitors and APR-246 (eprenetapopt) co-treatment is dependent on SLC7A11 phosphorylation.
Authors: Mlakar Vid , Oehme Ina , Lesne Laurence , Najafi Sara , Ansari Marc , Gumy-Pause Fabienne
Published: September 2022

Background
We previously demonstrated that APR-246 could be an efficient treatment option against neuroblastoma (NB), the most common pediatric extracranial solid tumor. APR-246’s mechanism of action is not completely understood and can differ between cell types. Here we investigate the involvement of well-known oncogenic pathways in NB’s response to APR-246.
Methods
A proteome profiler kinase assays and western blot analysis were used to identify the molecular pathways involved in the responses to APR-246. Bulk ATP levels were used to determine the viability of cells and the IC50 for APR-246. Cystine-FITC was used to measure the cellular uptake of cysteine. PmRNA5 was used to affect ERK1/2 and pshRNA1 was used to silence HSP27. An IMR-32 xenograft zebrafish embryo model was used to assess APR-246 and sulfasalazine efficacy in vivo.
Results
After APR-246 treatment, the most deregulated signaling protein identified was ERK1/2, an end-point kinase of the RAS-MAPK pathway. Induction of phospho-ERK1/2 resulted in increased glutathione (GSH) levels, increased cystine uptake and increased resistance of NB cells to APR-246. Using ERK1/2 inhibitors in combination with APR-246, we were able to categorize cells into synergistic and antagonistic groups. After co-treatment, these two groups differ by their levels of SLC7A11 and Hsp27 phosphorylation, cystine uptake and BIM expression. Using erastin and sulfasalazine, both inhibitors of SLC7A11 and activators of ferroptosis, we were able to reverse the antagonistic effects of ERK1/2 inhibitors and demonstrate a strong synergistic action in vitro and in vivo in zebrafish models.
Conclusions
These results demonstrated a pivotal role of the RAS-MAPK pathway in the NB cellular response to APR-246 via the modulation of intracellular concentrations of GSH and the transport of cystine, phosphorylation of Hsp27, and programed cell death. Combining APR-246 with RAS-MAPK pathway inhibitors can, in some cases, lead to antagonistic action, which can be reversed by combining APR-246 with the clinically approved drug sulfasalazine.
ENTAIL: Yet Another Amyloid Fibrils Classifier
Authors: Citarella Alessia Auriemma , Biasi Luigi Di , De Marco Fabiola , Tortora Genoveffa
Published: September 2022

Background: This research aims to increase our knowledge of amyloidoses. These disorders cause incorrect protein folding, affecting protein functionality (on structure). Fibrillar deposits are the basis of some wellknown diseases, such as Alzheimer, Creutzfeldt -Jakob diseases and type II diabetes. For many of these amyloid proteins, the relative precursors are known. Discovering new protein precursors involved in forming amyloid fibril deposits would improve understanding the pathological processes of amyloidoses.
Results: A new classifier, called ENTAIL, was developed using over than 4000 molecular descriptors. ENTAIL was based on the Naive Bayes Classifier with Unbounded Support and Gaussian Kernel Type, with an accuracy on the test set of 81.80%, SN of 100%, SP of 63.63% and an MCC of 0.683 on a balanced dataset.
Conclusions: The analysis carried out has demonstrated how, despite the various configurations of the tests, performances are superior in terms of performance on a balanced dataset.
Impact of clowning with Children and Adolescents in confinement according to the KINDL-r Questionnaire revised version
Authors: Valdebenito Victoria
Published: September 2022

Background
The COVID-19 pandemic forced measurement such as confinement. This article presents results of online clown workshops developed during confinement between October 2020 and August 2021 with children and adolescents of low socioeconomic status in Chile, which main aim was to promote children and adolescents’ quality of life.
Methods
Using a quantitative approach, a quasi-experimental design of a single group and a pre-posttest design, the Strengths and Difficulties Questionnaire and the KINDL-r Questionnaire revised version were used. One hundred and twenty-three caregivers responded the pretest, and 73 the posttest.
Results
Results revealed that 28% of participants improved their self-esteem, 26% significantly increased their physical and emotional well-being, 18% improved their family well-being, and 16% the well-being associated with friends.
Conclusion
These positive findings are consistent with literature about effects of clowns working in healthcare settings. However, more research is needed in other contexts.
Machine Learning Based Combination of Multi-omics Data for Subgroup Identification in Non-small Cell Lung Cancer
Authors: Khadirnaikar Seema , Shukla Sudhanshu , Prasanna SRM
Published: September 2022

NSCLC is a heterogeneous disease with a poor prognosis. Identifying novel subtypes can help classify patients with similar molecular and clinical phenotypes and treatment responses. This study uses a machine learning-based approach to compress the multi-omics (mRNA, miRNA, methylation, and protein expression) NSCLC data to a lower dimensional space. This data is subjected to consensus K-means clustering to identify the five novel clusters (C1-C5). Survival analysis of the resulting clusters revealed a significant difference in the overall survival of different clusters (p-value: 0.019). Each cluster was then molecularly characterized to identify specific molecular characteristics. We found that cluster C3 showed minimal genetic aberration with a high prognosis. Next, classification models were developed using data from each omic level to predict the subgroup of unseen patients. A decision-level model was then built using these classifiers, which was used to classify unseen patients into five novel clusters. We also showed that the multi-omics-based classification model outperformed single-omic-based models, and the combination of classifiers proved to be a more accurate prediction model than the individual classifiers. In summary, we have used ML models to develop a classification method and identified five novel NSCLC clusters with different genetic and clinical characteristics. This classification can prove to help decide the therapeutic option for NSCLC patients.
Posture adjustment method of large aircraft components based on multiple numerical control positioners
Authors: Chu Wenmin , Li Gen , Li Shuanggao , Huang Xiang
Published: September 2022

In the digital assembly system of large aircraft components (LAC), multiple numerical control positioners (NCPs) are usually used as actuators to adjust the position and posture of LAC to realize the docking of LAC. The posture adjustment mechanism (PAM) composed of multiple NCPs is a redundant actuated parallel mechanism (RAPM). The traditional full position control (FPC) method may lead to interference between NCPs, resulting in the deformation of NCPs and bracket, affecting the service life of the equipment and the accuracy of posture adjustment. This paper proposes a posture adjustment method based on hybrid control, which divides the motion axes of the NCPs into the position control axis and the force control axis to avoid the internal force of posture adjustment caused by the cooperative motion error of the NCPs. The driving force of the axis of the RAPM under the same posture adjustment trajectory is uncertain. To further reduce the internal force of posture adjustment, a driving force distribution method based on the dynamic model of PAM is proposed. Then, the principle of selecting the position control axis of the PAM is analyzed, and the optimization strategy of the position control axis based on the condition number of the Jacobian matrix is studied to improve the motion performance of the PAM. Finally, the posture adjustment experiment of LAC is carried out. The results show that the hybrid control method based on the optimum contact force can significantly reduce the interaction force between NCPs, and can effectively avoid the deformation of NCPs and brackets. The experimental results of posture adjustment accuracy verification show that the optimization strategy of position control axis makes the accuracy of single posture adjustment meet the requirements of LAC docking, which can effectively improve the docking efficiency of LAC.
Mechanical thrombectomy for ischemic stroke during Percutaneous Coronary Intervention for Acute Myocardial Infarction in a three- vessel disease patient: a case report and literature review
Authors: ABUHEIT EZALDIN , Lu FengYuan , Liu ShiChao , Abdun Mohammed Awadh , Nuh Abdifatah Mohamed , Jian LiGuo , Li En
Published: September 2022

A 49-year-old patient with previously known multivessel disease presented with myocardial infarction and underwent cardiac catheterization, during which he sustained a severe ischemic stroke as a complication of the procedure. This operation involved re-opening the right coronary artery (RCA), mechanical thrombectomy (MT) for the right middle cerebral artery, and recanalization via a radial and femoral approach. After follow-up with rehabilitation. One week later, interventional revascularization of the left anterior descending artery (LAD) and left circumflex (LCx) was performed successfully.
Tunable Topological Phases in a Natural MnSb2Te4/(Sb2Te3)2 superlattice
Authors: Guo Yanfeng , Zhang Xin , Zhang Shihao , Jiang Zhicheng , Huan Shuchun , Yang Yichen , Liu Zhengtai , Yang Song , Jiao Jinlong , Yu Litao , Xia Wei , Wang Xia , Yu Na , Zou Zhiqiang , Liu Yongsheng , Ma Jie , Shen Dawei , Liu Jianpeng
Published: September 2022

Intrinsic ferromagnetic superlattice with nontrivial topological properties is a fertile ground to explore extoic quantum properties, such as the quantum anomalous Hall effect, large tunneling magnetoresistance, etc., which would have potential applications in next-generation spintronic devices. In this work, combining magneto-transport measurements, first principles calculations, and angle-resolved photoemission spectroscopy studies, we find that in a newly synthesized natural van der Waals MnSb2Te4/(Sb2Te3)2 superlattice, the competing magnetic interactions give rise to a fragile ferromagnetic ground state, which whereas very easily enters into the antiferromagnetic states at higher temperatures. Moreover, the system can be forced in to a ferromagnetic state by very small vertical magnetic field. Interestingly, MnSb2Te4/(Sb2Te3)2 would stay in axion insulator states for both ferromagnetic and antiferromagnetic configurations, which are protected by inversion-symmetry and the combination of time-reversal and half lattice translation symmetries, respectively. The axion insulator state can be converted into a Weyl semimetal with hole doping, manifested by the notable intrinsic anomalous Hall effect. Our work thus provides an intrinsic ferromagnetic topological material which can be tuned into versatile topological phases by temperature, magnetic field, as well as carrier doping.
Astragaloside IV alleviates neuronal ferroptosis in ischemic stroke by regulating FTO-m6A-ACSL4 axis
Authors: Jin Zhenglong , Gao Wenying , Guo Fu , Liao Shaojun , Hu Mingzhe , Yu Tao , Yu Shangzhen , Shi Qing
Published: September 2022

Background
Ischemic stroke (IS) is a detrimental neurological disease with limited treatments options. Astragaloside IV (As-IV) was a promising bioactive constituent in the treatment of IS. However, the functional mechanism remains unclear.
Methods
IS cell and mice models were established by oxygen glucose deprivation /re-oxygenation (OGD/R) and middle cerebral artery occlusion (MCAO). RT-qPCR, Western blotting or Immunofluorescence staining were used to measure the gene expression. The N6-methyladenosine (m6A) levels were measured by MeRIP-qPCR and dot blot assays. CCK-8 and TUNEL staining were used to evaluate cell viability and apoptosis. TTC staining analyzed the infract area of brain tissues. The interplays of YTHDF3/ACSL4 and ATF3/FTO were analyzed by RNA-pull down, RIP, ChIP and dual-luciferase reporter assay.
Results
As-IV treatment promoted HT-22 and Neuro-2 cell viability and upregulated FTO levels in vitro and in vivo, as well as inhibited the levels of MDA, LDH, Fe2 + and ACSL4, while promoted the expression of GSH, SCL7A11 and GPX4. Knockdown of FTO, or overexpression of ACSL4 increased the infract size of brain tissues, neuron damage and the levels of MDA, LDH and Fe2+, while As-IV treatment reversed these changes. FTO regulated the m6A levels of ACSL4. YTHDF3 bound to ACSL4, and modulated its levels through m6A modification. ATF3 bound to FTO and positively regulated its levels. Knockdown of FTO or ATF3 increased the apoptosis of OGD/R cells, and promoted MDA, LDH and Fe2 + levels, while inhibited GSH expression. Knockdown of ACSL4, overexpression of FTO or treatment with As-IV reversed these effects.
Conclusion
As-IV promoted the transcription of FTO by upregulating ATF3, resulting in the decreased m6A levels of ACSL4, thus improving neuronal injury in IS by inhibiting ferroptosis.
2C-Net: Integrate Image Compression and Classification via Deep Neural Network
Authors: Liu Linfeng , Chen Tong , Liu Haojie , Pu Shiliang , Wang Li , Shen Qiu
Published: September 2022

Providing effective support for intelligent vision tasks without image reconstruction can save numerous computational costs in the era of big data. With the help of the Deep Neural Network (DNN), integrating image compression and intelligent vision tasks at a feature representation level becomes a new promising approach. But how to perform non-linear transformation for image compression and extract image patterns for intelligent vision tasks simultaneously within a shared DNN remains an open problem. In this paper, a versatile framework is studied to explore the common feature representations for both image compression and classification. A fully-shared latent representation is extracted in a more compact way to support compression and classification task. The General Feature Extraction and Feature-analytic Classifier are proposed to generate and utilize compact and general shared latent representation. Then the whole framework is joint optimized by considering multiple factors (i.e., rate, quality and accuracy). Extensive experiments are carried out to validate that the proposals can improve the performance of both learning-based image compression and classification.The results show that the proposed method outperforms conventional codecs like BPG and JPEG2000 in compression efficiency, while achieving acceptable accuracy on different datasets without image reconstruction.
Diabetes medications and cancer risk associations: a systematic review and meta-analysis of evidence over the past 10 years
Authors: Chen Yixian , Mushashi Fidela , Son Surim , Bhatti Parveen , Dummer Trevor , Murphy Rachel A.
Published: September 2022

Diabetes medications may modify the risk of certain cancers. We systematically searched MEDLINE, Embase, Web of Science, and Cochrane CENTRAL from 2011 to March 2021 for studies evaluating associations between diabetes medications and the risk of breast, lung, colorectal, prostate, liver, and pancreatic cancers. A total of 92 studies (3 randomized controlled trials, 64 cohort, and 25 case-control studies) were identified, involving 171 million participants. Inverse relationships with colorectal (RR = 0.85; 95% CI = 0.78–0.92) and liver cancers (RR = 0.55; 95% CI = 0.46–0.66) were observed in biguanide users. Thiazolidinediones were associated with lower risks of breast (RR = 0.87; 95% CI = 0.80–0.95), lung (RR = 0.77; 95% CI = 0.61–0.96) and liver (RR = 0.83; 95% CI = 0.72–0.95) cancers. Insulins were negatively associated with breast (RR = 0.90; 95% CI = 0.82–0.98) and prostate cancer risks (RR = 0.74; 95% CI = 0.56–0.98). Positive associations were found between insulin secretagogues and pancreatic cancer (RR = 1.26; 95% CI = 1.01–1.57), and between insulins and liver (RR = 1.74; 95% CI = 1.08–2.80) and pancreatic cancers (RR = 2.41; 95% CI = 1.08–5.36). Overall, biguanide and thiazolidinedione use carried no risk, or potentially lower risk of some cancers, while insulin secretagogue and insulin use were associated with increased pancreatic cancer risk.
A MALDI-TOF MS-based discriminant model to distinguish azole-resistant Aspergillus fumigatus strains
Authors: Yamashita Koji , Yaguchi Takashi , Miwa Emi , Kiyuna Tomohiko , Shima Keisuke , Ito Junko , Arai Teppei , Watanabe Akira , Ban Sayaka
Published: September 2022

Aspergillus fumigatus is the major causative agent of aspergillosis in immunosuppressed hosts and patients with chronic pulmonary diseases. Recently, azole resistance of this fungus has become a problem worldwide; thus, rapid detection of resistant strains is desirable in clinical practice. In this study, we established a matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) combined with multivariate and discriminant analysis to detect azole-resistant A. fumigatus strains. The score plot from a partial least squares discriminant analysis clearly separated resistant and susceptible strains, regardless of the culture period. The discriminant analysis using the support-vector machine algorithm based on a dataset for strains cultured on potato dextrose agar for 3 days showed the best performance, with a correct answer rate of 84.75–99.85%. We found a MS peak (4359.5 m/z) specific to some azole-resistant strains with a 34-bp tandem repeat in the promoter region of cyp51A. These tandem repeat strains are extremely rare in Japan. Instead, most resistant strains in Japan have point mutations in cyp51A. No specific biomarker for strains with point mutations was found, but it was possible to detect these resistant strains using a model for point-mutation strains.