bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of free farmland transfer on the adoption of conservation tillage technology -- Empirical evidence from the plot level of China
Authors: CHEN Jia , XU Jingwen , JI Xing , ZHANG Hongxiao
Published: May 2022

At present, there are a large number of free farmland transfer without monetary or physical rents in rural China. It is relatively worthwhile to verify whether the transferees who transfer in farmland for free, the actual operators of farmland, would adopt the conservation tillage technology, which is crucial in protecting farmland quality and improving agricultural production efficiency. Based on the data of 527 plots surveyed by China Land Economic Survey (CLES) in Jiangsu Province in 2020, this paper employs Negative Binomial Regression (NBR), Poisson Regression with Endogenous Treatment Effects (ETPR) and Endogenous Switching Regression (ESR). Results show that: (1) Compared with the transferees who transfer into farmland with compensation, the free transfer is not conducive to the transferees’ adoption of five CTTs such as straw mechanical returning, soil testing and formulated fertilization. Specifically, the total number of technology adoptions by transferees who transfer in farmland without compensation is decreased by 1.977. The result is still robust after replacing the dependent variable. (2) Further heterogeneity analysis results of different types of technologies show that the number of labor-saving CTTs such as straw mechanical returning adopted by the transferees of free transfer decreases by 0.231, and the number of labor-intensive tillage technologies such as soil testing and formulated fertilization decreases by 2.496. Thus, free transfer has a stronger inhibitory effect on the transferees’ adoption of labor-intensive CTTs. Therefore, for the most developing countries including China, the governments should continue to improve the farmland factor market oriented by price mechanism and implement targeted conservation tillage technology according to the different degree of transfer marketization in different places.
Joint State and Parameter Estimation of Nonlinear Dynamical Systems Through Alternating Optimization
Authors: Cheng Changming , Lin Miaomiao , Zhang Guanzhen , Peng Zhike , Meng Guang
Published: May 2022

A key challenge in the data-driven identification method of nonlinear dynamical systems is developing methods robust to measurement error. Many existing methods either depend on de-noising prior to learning or have a poor identification performance. This paper proposes a novel joint state and parameter estimation method for nonlinear dynamical systems through alternating optimization. The new method can effectively remove or at least attenuate the effect of noise via alternatingly updating the state variables and parameters in nonlinear dynamical systems. The proposed identification framework mainly contains four steps. Firstly, initial estimations of state variables (displacement and velocity) are derived by using the Reproducing Kernel Hilbert Space (RKHS)-based de-noising method. Secondly, using the initial estimation of state variables, the nonlinear structure and parameters are identified by using the sparse regression and Duhamel’s integral, which can correctly select the contributing nonlinear component and identify the parameters. By using the Duhamel’s integral, the second derivative of the displacement signal which is sensitive to noise is no longer required. Thirdly, to further improve the identification accuracy, the state variables are updated based on the identified structure and parameters using the numerical integration. Finally, estimation of the nonlinear structure and parameters in step 2 and update of state variables in step 3 are alternatingly optimized until convergence. The numerical simulations and a dynamic experiment validate the effectiveness of the new identification method developed in this paper.
Understanding the multilevel determinants of clinicians’ imaging decision-making: Setting the stage for de-implementation of low-value imaging
Authors: Hwang Soohyun , Birken Sarah A. , Nielsen Matthew E. , Elston-Lafata Jennifer , Wheeler Stephanie B. , Spees Lisa P.
Published: May 2022

Background: De-implementation requires targeting multilevel determinants of low-value care. The objective of this study was to identify multilevel determinants of imaging for prostate cancer (PCa) and asymptomatic microhematuria (AMH), two common urologic conditions that have contributed substantially to the approximately $30 billion spent annually on unnecessary imaging in the US.Methods: We used a convergent mixed-methods approach involving survey and interview data. Using a survey, we asked 33 clinicians (55% response rate) to indicate their imaging approach to 8 clinical vignettes designed to elicit responses that would demonstrate guideline-concordant/discordant imaging practices for describing patients with PCa or AMH. A subset of survey respondents (N=7) participated in semi-structured interviews guided by the Theoretical Domains Framework (TDF) and Consolidated Framework for Implementation Research (CFIR), whose combination has offered comprehensive understanding of multilevel implementation determinants. We analyzed the interviews using a directed content analysis approach. For each clinical condition, we identified relevant constructs/domains based on the frequencies with which the construct/domain was mentioned across interviews. We then identified subthemes within each construct/domain and examined subtheme similarities and differences across the two clinical conditions.Results: The majority of clinicians chose guideline-concordant imaging behaviors for PCa; guideline-concordant imaging intentions were more varied for AMH. Imaging decisions for both PCa and AMH were often driven by national guidelines from major professional societies. However, when clinicians felt that guidelines were inadequate, they reported that their decision-making was influenced by their knowledge of recent scientific evidence, past clinical experiences, and the anticipated benefits of imaging (or not imaging) to both the patient and the clinician. In particular, clinicians referred to patients’ anxiety and uncertainty which were, at times, resolved through more intensive diagnostic imaging. Patients’ clinical factors also informed clinicians’ imaging decisions. For AMH patients, clinicians additionally expressed concerns regarding legal liability risk.Conclusions: Our study identified comprehensive multilevel determinants of imaging to inform development of de-implementation interventions to reduce low-value imaging, using CFIR+TDF, which we found useful for identifying determinants of de-implementation. De-implementation interventions should be tailored to address the contextual determinants that are specific to each clinical condition.
Assessing the specification of modelling language semantics: A study on UML PSSM
Authors: Elekes Márton , Molnár Vince , Micskei Zoltán
Published: May 2022

Modelling languages play a central role in developing complex, critical systems. Having a precise, comprehensible, and high-quality modelling language specification is essential to all the different stakeholders using, implementing, or extending the language. Many good practices can be found that improve the understandability or consistency of the languages' semantics. However, designing a modelling language intended for a large audience is still challenging. In this paper, we investigate how to assess the specification of modelling language semantics: (i) how it helps professionals to understand the language (ii) whether it contains errors, contradictions, ambiguities, and (iii) how suitable it is to assess the correctness of the related modelling tools. We identified the various stakeholders' viewpoints on the language and argued why understanding the semantics is crucial for all of them, although on different levels that can be supported by different artefacts. Next, we assessed a state-of-the-art specification for a general-purpose modelling language, the Precise Semantics of UML State Machines (PSSM). We reviewed the text of the specification, analysed and executed PSSM's conformance test suite, and categorized our experiences according to questions that are generally relevant for modelling languages. Finally, we made recommendations for improving the development of future modelling languages by representing the semantic domain and traces more explicitly, applying diverse test design techniques to obtain conformance test suites, and using various tools to support early-phase language design.
Origin of active sites on silica-magnesia catalysts and control of reactive environment in the one-step ethanol-to-butadiene process
Authors: Chung Sang-Ho , Li Teng , Shoinkhorova Tuiana , Ramirez Adrian , Mukhambetov Ildar , Abou-Hamad Edy , Shterk Genrikh , Telalovic Selvedin , Dikhtiarenko Alla , Sirks Bart , Lavrik Polina , Tang Xinqi , Weckhuysen Bert , Bruijnincx Pieter , Gascon Jorge , Ruiz-Martinez Javier
Published: May 2022

Wet-kneaded silica–magnesia is a benchmark catalyst for the one–step ethanol-to-butadiene Lebedev process. Magnesium silicates, formed during wet-kneading, have been proposed as active sites responsible for butadiene formation, and their catalytic performance has been mainly explained by the variations in the ratio of acid and base sites. While the Lebedev process was developed in the 1930s, However, a detailed insight into how the peculiar, yet essential wet-kneading synthesis leads to the generation, location, and catalytic role of magnesium silicates has not been fully established. Here, we demonstrate that magnesium silicates formation occurs via dissolution of Si and Mg subunits from SiO2 and Mg(OH)2 precursors, initiated by the alkaline pH of the aqueous wet-kneading medium, followed by cross-deposition of the dissolved species on the precursor surfaces. Building on these new insights, two individual model systems (Mg/SiO2 and Si/MgO) were synthesized, representative of the constituents of the wet-kneaded silica–magnesia catalyst, by selective dissolution/deposition induced by pH alteration of the aqueous wet-kneading medium. Using these model catalysts, we demonstrate that the location of the magnesium silicates (i.e., Mg on SiO2 or Si on MgO) governs not only their chemical nature but also the ethanol adsorption configuration, which ultimately cause the catalyst material to be selective mainly for ethylene or butadiene. We demonstrate close proximity at the particle level of the of acid and basic sites is a prerequisite to promote the butadiene formation. The insights gained from the new structure–performance relationships that correlate catalytic activity with types and nature of magnesium silicates can offer new possibilities for the development of next generation Lebedev catalysts.
Effects of a monoclonal antibody against (pro)renin receptor on gliomagenesis
Authors: Fujimori Takeshi , Shibayama Yuki , Kanda Takahiro , Suzuki Kenta , Ogawa Daisuke , Ishikawa Ryo , Kadota Kyuichi , Matsunaga Toru , Miyake Keisuke , Nishiyama Akira , Tamiya Takashi
Published: May 2022

Glioblastoma is characterized by a strong self-renewal potential and poor differentiated state. We have reported previously that the (pro)renin receptor [(P)RR] is a potential target for glioma therapy by silencing the (P)RR gene. Here, we have examined the effects of a monoclonal antibody against (P)RR on gliomagenesis. Methods: Human glioma cell lines (U251MG and U87MG) and a glioma stem cell line (MGG23) were used for the in vitro study. The expressions of the Wnt/β-catenin signaling pathway (Wnt signaling pathway) components and stemness markers were measured by Western blotting. The effects of the (P)RR antibody on cell proliferation, sphere formation, apoptosis and invasion were also examined. Subcutaneous xenografts were also examined in nude mice. Results: Treatment with the (P)RR antibody reduced expression of Wnt signaling pathway components and stemness markers. Furthermore, the (P)RR antibody reduced cell proliferation and decreased sphere formation significantly. The treatment also suppressed invasion and induced apoptosis. In a subcutaneous xenograft model, systemic administration of the (P)RR antibody reduced tumor volume significantly. Conclusion: These data show that treatment with the (P)RR antibody is a potential therapeutic strategy for treating glioblastoma.
Potential Off-flavour Scavenging Role of Isoflavones in Soybean
Authors: Kumar Sandeep , Banerjee Sagar , Kaur Amandeep , Sasi Minnu , Kumari Sweta , Sachdev Archana , Dahuja Anil
Published: May 2022

Soybean (Glycine max (L.) Merr) is a nutrient-rich crop but has limited consumer acceptability because of the presence of off-flavour. Owing to the ubiquity of isoflavones in soybean, their inherent antioxidant potential, and inhibitory effect on lipoxygenase activity, their sensorial attribute in mitigating off-flavour is currently being envisaged. We estimated the content and composition of isoflavones in 17 soybean cultivars and established the correlation between isoflavone profile and lipid peroxidation, which was measured in terms of Thiobarbituric acid (TBA) number and carbonyl value. The results showed a significant negative correlation of these parameters with the total isoflavone content and genistein: daidzein ratio. Besides, expression analysis of a key gene involved in isoflavone biosynthesis i.e., isoflavone synthase (IFS1 and IFS2) in contrasting soybean genotypes during seed development revealed a higher expression of both isoforms in Bragg (High isoflavone) as compared to PUSA 40 (Low isoflavone) at different stages of seed development accompanied by more isoflavone accumulation. The cloning and in silico analysis of IFS isoforms revealed a more significant interaction with other biosynthesis enzymes by the IFS2, indicating its more substantial role in isoflavone synthesis. IFS2 overexpression thus can be a valuable target to increase isoflavone biosynthesis, thereby scavenging off-flavour.
Demographic, socio-economic, obstetric, and behavioral factors associated with small-and large- for-gestational-age from a prospective, population-based pregnancy cohort in rural Nepal: A secondary data analysis
Authors: Hazel Elizabeth , Mohan Diwakar , Zeger Scott , Mullany Luke C. , Tielsch James M. , Khatry Subarna K. , Subedi Seema , LeClerq Steven C. , Black Robert E. , Katz Joanne
Published: May 2022

BackgroundIn South Asia, a third of babies are born small-for-gestational age (SGA) accounting for a quarter of all neonatal deaths. The risk factors are well described in the literature, but many studies are in high-and-middle income countries or measure SGA on facility births only. There are fewer studies that describe the prevalence of risk factors for large-for-gestational age (LGA) in low-income countries. We aim to describe the factors associated with SGA and LGA in a population-based cohort of pregnant women in rural Nepal. MethodsThis is a secondary data analysis of a community-based trial where women were assessed for pregnancy approximately every five weeks. Demographic, socio-economic status (SES), medical/obstetric history, and timing of last menstruation were collected on pregnant women at enrollment. Vital signs, illness symptoms, and antenatal care (ANC) attendance were collected throughout the pregnancy and neonatal weight was measured for live births. We conducted multivariate analysis using multinomial logistic regression. Outcomes were SGA, LGA compared to appropriate-for-gestational age (AGA) and were multiply imputed using birthweight recalibrated to time 0, at delivery.Results In the adjusted analysis, SGA was associated with lower SES, zero parity, interpregnancy intervals less than 18 months, poor appetite/vomiting in the second trimester, and swelling of hands/face in the third trimester. Parity greater than five, male fetal sex, and increased weight gain were protective for SGA. Many of these factors were inversely associated with LGA. Additionally, four or more ANC visits and respiratory symptoms in the third trimester were negatively associated with LGA, and maternal age <18 years and respiratory symptoms in the second trimester were positively associated with LGA. Conclusions Our findings are in line with known risk factors for SGA. Because the prevalence and mortality risk of LGA babies is low in this population, it is likely LGA status does not indicate underlaying illness. High quality antenatal care, monitoring for appropriate gestational weight gain and increased monitoring of women with high-risk pregnancies may reduce prevalence and improve outcomes of SGA babies. Trial RegistrationThe study used in this secondary data analysis was registered at Clinicaltrials.gov NCT01177111.
Identification of Necroptosis-Related Long Noncoding RNAs for Immunotherapy Selection and Prognosis Prediction in Patients with Colorectal Cancer
Authors: Chen Zhihua , Lin Yilin , Lin Suyong , Yang Xiaoyu , Chen Shao-Qin
Published: May 2022

Background: Tumor recurrence and metastasis lead to a poor prognosis in colorectal cancer (CRC). Necroptosis is closely related to the tumor microenvironment (TME) and affects tumor recurrence and metastasis. We aimed to stratify CRC patients according to necroptosis-related long noncoding RNAs (lncRNAs), which can be used to not only evaluate prognosis and improve precision medicine in clinical practice but also evaluate the efficacy of immunotherapy and guide the selection of immunotherapeutic methods. Methods: A lncRNA expression profile was collected from The Cancer Genome Atlas (TCGA). Necroptosis-related lncRNAs were identified by coexpression analysis. Cox regression analysis identified a necroptosis-related lncRNA signature. Then, the value of this signature was comprehensively and multidimensionally evaluated, and its fidelity was assessed with clinical CRC data and compared with that of six other lncRNA signatures for CRC prognosis prediction. Gene set enrichment analysis (GSEA), TME analysis and prediction of the half-maximal inhibitory concentration (IC50) were also performed according to the risk score (RS) of the signature. Results: An 8-lncRNA signature significantly associated with overall survival (OS) was constructed, and its fidelity was validated with clinical CRC data. Most of the areas under the receiver operating characteristic (ROC) curve (AUCs) for 1-, 3- and 5-year OS for this signature were higher than those for the other six lncRNA signatures. OS, disease-specific survival (DSS) and the progression-free interval (PFI) were all significantly poorer in the high-risk group. The RS of the signature showed good concordance with the predicted prognosis, with AUCs for 1-, 3- and 5-year OS of 0.79, 0.81 and 0.77, respectively. Additionally, the calibration plots for this signature combined with clinical factors could effectively improve the ability to predict OS. The RS was correlated with tumor stage, lymph node metastasis and distant metastasis. Most of the enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) terms were tumor metastasis-related pathways in the high-risk group, which showed greater infiltration of immunosuppressive cells, such as cancer-associated fibroblasts (CAFs), hematopoietic stem cells and M2 macrophages, but fewer infiltrating antitumor effector immune cells, such as CD8+ T cells and regulatory T cells (Tregs). We explored additional potential immune checkpoint genes and immunotherapeutic and chemotherapeutic drugs with relatively low IC50 values. Conclusions: We identified a signature with strong fidelity that could stably predict prognosis and might be implicated in the TME and metastasis of CRC. Furthermore, additional potential immune checkpoint genes and immunotherapeutic and chemotherapeutic drugs were explored.
Potentially inappropriate medications in older Chinese outpatients based on the Beers criteria and Chinese criteria
Authors: Zhang Ying , Chen Zhaoyan , Tian Fangyuan
Published: May 2022

Objective
Polypharmacy increases the prevalence of potentially inappropriate drugs (PIMs) among older persons, lowering their quality of life. This study aimed to compare the prevalence of PIMs in older Chinese outpatients according to the Beers criteria and the Chinese criteria and to analyze the risk factors. Second, we describe the differences between the two criteria, focusing on the inappropriate prescription of drugs in older outpatients.
Methods
In Chengdu, Southwest China, a retrospective study was undertaken using electronic medical data from 9 medical institutions. Outpatients above the age of 60 who were treated in the Geriatrics Center of these medical institutions were included. The Beers criteria and the Chinese criteria were used to evaluate the PIM status of older outpatients, and logistic regression was used to identify potential risk factors for PIMs.
Results
There were 44,458 prescriptions from 2016 to 2018. The prevalence of PIMs among older outpatients was 30.05% (according to the Beers criteria) and 35.38% (according to the Chinese criteria). Estazolam, hydrochlorothiazide and alprazolam were the top three PIMs in the Beers criteria, while the top three PIMs in the Chinese criteria were clopidogrel, estazolam and insulin. The prevalence of PIMs was associated with age, the number of diseases and the number of drugs. PIMs were shown to be more common in patients aged 70 and above, with more than 2 kinds of diseases and more than 4 kinds of drugs.
Conclusion
PIMs were shown to be common among older outpatients in China, according to this study. The detection rate of the Chinese criteria was higher than that of the Beers criteria.
Improvement Learning Using a Fully Integrated Neuro-Inspired Memristor Chip
Authors: Wu Huaqiang , Gao Bin , Zhang Wenbin , Yao Peng , Liu Qi , Wu Dong , Zhang Qingtian , Xu Minghong , Zhou Ying , Zhu Zhenhua , Cai Yi , Wu Dabin , Tang Jianshi , Qian He , Wang Yu
Published: May 2022

Future neuro-inspired computing chips will feature high energy efficiency and extensive learning capabilities. Among these features, improvement learning is of great importance for edge intelligence devices to adapt to different application scenes and owners. However, current technologies for training neural networks greatly rely on large-scale computers, which are based on von Neumann architectures and complex digital circuits. The huge energy costs of moving massive data between computing and memory units and processing high-precision data hinder the implementation of improvement learning on edge devices. Here, we report improvement learning with a low-power full-system-integrated memristor-based neuro-inspired computing chip. We propose a memristor-featured analogue in-memory computing architecture for implementing on-chip learning efficiently and integrate ~160K memristor cells with complete peripheral circuits in a complementary metal-oxide-semiconductor (CMOS)-compatible technology. We demonstrate the on-chip learning of both new samples and new classes across various tasks, including motion control, image classification, and speech recognition. The energy consumption of the memristor chip for learning is three orders of magnitudes lower than that of a central processing unit (CPU)-based system based on hardware system measurements. This study is an important step toward the learning chips with much higher energy efficiency, which will facilitate the development of future smart edge devices that can adapt to all kinds of special scenes.
Personal risk or societal benefit? Investigating adults’ support for COVID-19 childhood vaccination
Authors: Chiavenna Chiara , Leone Laura P. , Melegaro Alessia , Rotesi Tiziano , Bokemper Scott E. , Paintsil Elliott E. , Malik Amyn A. , Huber Gregory A. , Omer Saad B. , Cucciniello Maria , Pin Paolo
Published: May 2022

Parental hesitancy poses a serious threat to the success of the COVID-19 childhood vaccination campaign. We investigate whether adults' opinions on childhood vaccination can be influenced via two survey experiments in Italy (n=3,524 participants) and the UK (n=3,066 participants). Respondents were randomly assigned to: a “risk treatment” that highlighted the potential risks of COVID-19 to a child, a “herd immunity treatment” that emphasized the community benefits of pediatric vaccination, or a control message. Participants’ probability of supporting COVID-19 childhood vaccination was then assessed on a 0-100 scale. We find that the “risk treatment” reduced the proportion of Italian parents strongly against vaccination by up to 29.6%, while increasing the proportion of neutral parents by up to 45.0%. The “herd immunity treatment”, instead, was only effective among non-parents, resulting in a lower proportion of individuals against pediatric vaccination and a higher proportion of individuals in favor (both shifted by around 20%).
Dietary Astaxanthin Supplementation could regulate the Gut-Kidney axis to protect against Kidney Impairment in Type 2 Diabetes mice
Authors: HA Mei , YANG Yuhui , LIU Changjiang , WU Mingzhu , Gong Ting , CHEN Zongyue , LUO Yu
Published: May 2022

The authors have requested that this preprint be removed from Research Square.
Association between HBA1C, hyperlipidemia, ankle-brachial index (ABI), and toe-brachial index (TBI) with wound healing in diabetic foot ulcer after angioplasty
Authors: Sobhiyeh Mohammadreza , Rai Alireza , Molavi Masoumeh , Kermanshahi Amirreza Jafari
Published: May 2022

Background
Diabetic foot ulcer (DFU) is a serious complication of diabetes that can lead to severe consequences if left untreated. Revascularization with balloon angioplasty is a method of management of peripheral arterial disease, and factors that can affect wound healing are of interest. The aim of the present study was to investigate the association between HBA1C, hyperlipidemia, ankle-brachial index (ABI), and toe-brachial index (TBI) with wound healing after balloon angioplasty in patients with DFUs.
Methods
Ninety patients with DFUs who underwent balloon angioplasty were included. Baseline HBA1C, hyperlipidemia, ABI, and TBI were recorded. These were measured once more three months after angioplasty. Then, based on wound healing (satisfactory or failed wound healing) as the outcome measure, patients were divided into two groups and the gathered variables were compared.
Results
The wound healing rate at 3-month follow-up was 62.2% (56 out of 90 achieved healing of ulcer). There was no statistically significant difference between the two groups in terms of gender, age, and body mass index (BMI). Baseline values of HbA1c were significantly higher in those who failed wound healing (9.6 ± 1.2% vs. 9.0 ± 1.2%); P = 0.01. The average values of ABI (0.77 vs. 0.8; P = 0.04) and TBI (0.51 vs. 0.60; P < 0.001) were significantly lower in the group with failed ulcer healing. The similar findings were observed at three-month follow-up measurements. There was no significant difference between the groups regarding the frequency of hyperlipidemia.
Conclusion
Baseline and post-angioplasty measures of HbA1c, ABI, and TBI could affect wound healing in patients with DFU and lower limb ischemia undergoing balloon angioplasty.
Correlation between serum 25-OH-vitamin DLevel and diabetic foot ulcer in elderly diabetic patients
Authors: Wang Fenglin , Xu Jia , Zhu Di , Yang Caizhe
Published: May 2022

Objective To investigate the relationship between the level of 25-OH-vitamin D [25 (OH) D] and diabetic foot ulcers (DFU) in aged Diabetes Mellitus (DM) patients. Methods from January 2020 to March 2022, 339 elderly DM patients, aged 60 to 90 years old, hospitalized in the Department of Endocrinology, Air Force Special Medical Center, were selected and divided into DFU group (n=204) and DM group (n=135) according to the presence or absence of DFU. The clinical and biochemical characteristics of the two groups were compared. The change of 25 (OH) D and its relationship with DFU was analyzed. Results SBP and BUN in DFU group were higher than those in DM group, and the course of disease was longer than that in DM group. The levels of TC, TG, HDL-C, ALT, AST, ALB, Hb, HCT and serum 25 (OH) D in DFU group were lower than those in DM group, the differences were statistically significant (p < 0.05). Logistic regression analysis showed that increased serum 25 (OH) D level was a protective factor for DFU in DM patients (p < 0.05). In this study, 80.5% of elderly DM patients suffered from vitamin D deficiency, and the proportion of vitamin D deficiency in DFU group was significantly higher than that in DM group. The difference was statistically significant (p < 0.05). With the increase of Wagner grade, the level of 25 (OH) D gradually decreased (p = 0.004). Multiple comparisons showed that the level of 25-OH-vitamin D in Wagner grade 2 patients was significantly higher than that in wager Grade 4 patients (P < 0.05). Spearman correlation analysis showed that the serum 25-(OH)-D level was negatively correlated with DFU (P =0.001, R =-0. 182). Conclusion vitamin D deficiency or insufficiency is common in elderly DM patients, and is more serious in DFU patients.
A DNA-launched reverse genetics system of feline calicivirus identified 3′ UTR as an essential element for its replication
Authors: Cheng Jie , Tang Aoxing , Chen Jing , Zhang Da , Meng Chunchun , Li Chuanfeng , Wei Hulai , Liu Guangqing
Published: May 2022

Virulent systemic feline calicivirus (VS-FCV) is a newly emerging pathogen associated with severe and acute virulent systemic disease, characterized with jaundice, oedema and high mortality (approximately 70%) in cat population. Currently, VS-FCV has a worldwide spread, but deficient in effective vaccines or therapeutic options to combat infection. As a result, VS-FCV is posing a serious threat to the health of felines. So far, the genomic characteristics and function of VS-FCV are poorly understood, and the underlying mechanism for its increased pathogenicity is also enigmatic. Reverse genetic system is proven to be a powerful tool to study the molecular biology of RNA viruses, but the reverse genetic system of VS-FCV has not been reported. In this study, we pioneered simple and fast construction of a plasmid-based VS-FCV reverse genetics system that efficiently produced infectious progeny virus in CRFK cells. Using this system, we next investigated the role of 3' untranslated region (UTR) and poly (A) tail on determining infectivity and replication of VS-FCV. The results showed that 3' UTR was a key element for maintaining the infection and replication capacity of VS-FCV. In addition, we found that the poly (A) tail was important for maintaining the infectivity of VS-FCV. In detail, if the infectious clone of VS-FCV lacks the poly (A) tail, or its poly (A) tail length is less than 28 bases, it failed to rescue any infectious progeny virus. In conclusion, we successfully established a rapid and efficient VS-FCV reverse genetic system, which provides a good platform for future research on the gene function and pathogenesis of VS-FCV. The effects of 3' UTR and poly (A) tail on VS-FCV infectivity and replication also provided new clues to the pathogenesis of VS-FCV.
Differences between CVID Granulomatosis and Sarcoidosis: Clinical, Immunological and Histopathological Comparison
Authors: Viallard Jean-François , Lescure Maëlig , Oksenhendler Eric , Blanco Patrick , Visentin Jonathan , Parrens Marie
Published: May 2022

Common variable immunodeficiency granulomatous disease (CVID-GD) is a serious complication that occurs in 8–22% of CVID patients and can mimic sarcoidosis with which it shares certain clinical, biological and radiological features. However, no study to date has compared the two pathologies immunologically and histologically. Then, we analyzed the blood cell immunohistochemical-labeling profiles and the immunological-histological features of different biopsy samples from 10 patients with CVID-GD and compared them to those of with biopsy-proven sarcoidosis. Specifically, we wanted to know whether or not the signaling abnormalities observed in sarcoidosis granulomas are also present in CVID. The CVID-GD immunological profile differs markedly from that of sarcoidosis, with a profound memory-cell deficit, strong CD8 + T-cell activation and altered balance in follicular helper-T cells (TFH) subsets in the blood. Morphological differences were found between CVID-GD histology and classical sarcoidosis, mainly the former’s notable/extensive lymphoid hyperplasia associated with granulomas not observed in the latter. All organs involved with CVID-GD contained several TFH1 cells the granulomatosis, while TFH lymphocytes were inconstantly and more weakly expressed in sarcoidosis. Moreover, CVID and sarcoidosis granulomas expressed the signal transducer and activator of transcription (STAT)1 and STAT3 factors, regardless of the organ studied and without any significant difference between them. Our results suggest that the macrophage-activation mechanism in CVID resembles that of sarcoidosis, thereby suggesting that JAK-STAT-pathway blockade might be useful in currently difficult-to-treat CVID-GD.
In-shoe pressure analysis in patients with a history of diabetes-related foot ulceration: a mixed methods study
Authors: McDonogh Clare , Nube Vanessa , Frank Georgina , Twigg Stephen , Penkala Stefania , Holloway Samantha , Snyder Robert
Published: May 2022

Background
Medical grade footwear (MGF) with demonstrated plantar-pressure reducing effect is recommended to reduce the risk of diabetes-related foot ulceration (DFU). Efficacy of MGF relies on high adherence (≥ 80%). In-shoe pressure analysis (IPA) is used to assess and modify MGF, however, there is limited evidence for the impact on patient adherence and understanding of MGF. The primary aim of this study was to determine if self-reported adherence to MGF usage in patients with previous DFU improved following IPA compared to adherence measured prior. The secondary aim was to determine if patient understanding of MGF improved following in-shoe pressure analysis.
Methods
Patients with previous DFU fitted with MGF in the last 12 months were recruited. The first three participants were included in a pilot study to test procedures and questionnaires. MGF was assessed and modified at Week 0 based on findings from IPA using the Pedar system (Novel). Patients completed two questionnaires, one assessing patient adherence to MGF at Week 0 and Week 4, the other assessing patient understanding of MGF before and after IPA at week 0. Patient understanding was measured using a 5-point Likert scale (strongly disagree 1 to strongly agree 5). Patient experience was assessed via a telephone questionnaire administered between Weeks 0–1.
Results
15 participants were recruited, and all completed the study. Adherence of ≥ 80% to MGF usage inside the home was n = 2 (13.3%) pre-IPA and n = 3 (20.0%) at Week 4. Outside the home, ≥ 80% adherence to MGF was n = 8 (53.3%) pre-IPA, and n = 12 (80.0%) at Week 4. All participants reported that undergoing IPA improved their understanding of the value of MGF and that undergoing the intervention was worthwhile and beneficial.
Conclusions
Self-reported adherence inside the home demonstrated minimal improvement after 4 weeks, however, adherence of ≥ 80% outside the home increased by 27%, with 80% of all participants reporting high adherence at Week 4. Participants rated their learnings from the experience of IPA as beneficial.
Africa Union (AU) Africa Centers for Disease Control and Prevention Role in the fight against COVID-19 in Africa: An Analysis of Frontline Health Workers' Perspectives
Authors: Kipo-Sunyehzi Daniel Dramani
Published: May 2022

Background: This article examines the role of the Africa Union (AU) Africa Centers for Disease Control and Prevention (Africa CDC) and other international partners in the fight against the global pandemic on the continent (Africa). It analyzes the governance structure of the Africa CDC and the policy strategies to slow the virus and at the best end the pandemic. The Africa CDC works through its regional offices across the continent intending to strengthen the public health systems of AU member states in response to disease outbreaks. In this regard, the perspectives of frontline health workers were analyzed in an AU member state (Ghana). Methods: Data is obtained largely from qualitative sources through in-depth interviews, focus groups discussion, the use of official documents and some direct observations in the field (in offices and health facilities). Purposive and snowball sampling methods were utilized in which 40 participants took part in the study including national, regional and local level workers who worked or interacted directly with clients (COVID-19 patients, persons with suspected cases among others). Results: The results show that many international partners are identified as key partners that are directly involved in the fight against the novel coronavirus disease 2019 (COVID-19) in Africa. It is interesting to note that the World Health Organization, UNICEF and the US CDC are more prominent in the fight against COVID-19 in Ghana than the Africa CDC. The reason for this is that the Africa CDC worked through its Regional Coordinating Centers (RCC) instead of working directly with the AU member states. Thus, the Africa CDC occupied the fourth position of the international partners who played crucial roles in the fight against the global pandemic in Ghana. Conclusion: The study concludes that strengthening public health systems is crucial in Africa and that the fight against COVID-19 is a collective one for all states and international partners. It recommends that the Africa CDC should find a way to work directly with the AU member states including Ghana.
Evaluation of molecular-level changes of Programmed cell Death Ligand-1 after radiotherapy in a BALB/c CT26 colorectal mouse tumor model
Authors: Chamani Fateme Khani , Shabani Mahdi , Moradi Afshin , Alinejad Maedeh , Chalbatani Ghanbar Mahmoodi , Hamblin Michael R , Jalali Seyed Amir
Published: May 2022

The effects of radiation therapy (RT) for cancer can be systemic and partially mediated by the immune system. However, radiation alone is unlikely to transform an immunosuppressive environment into an immunostimulatory one. Therefore, an effective combination of radiation therapy and immunotherapy may provide a new more efficient treatment approach. Here we investigated how the expression of programmed cell death-ligand 1 (PD-L1) in the microenvironment of the tumor varied in different RT regimens with the same Biologically Effective Dose (BED). In this study, female BALB/c mice inoculated with CT26 tumor cells were irradiated with three different RT regimens using the same Biologically Effective Dose (BED) of 40 Gray (Gy). These included Ablative RT (1*15 Gy), Hypo-fractionated RT (2*10 Gy), and Conventional RT (10*3 Gy). PD-L1 expression was analyzed with immunohistochemical staining on days 2, 20, and when the size of tumors had reached 2 cm2 after RT. All treated groups expressed PD-L1, but the group receiving single ablative high dose RT showed higher expression compared to the other groups. No significant differences in PD-L1 expression were observed at different times in the same group. These findings showed that different regimens of RT have different effects on the tumor microenvironment (TME), so a combination of RT and immune checkpoint blockade could be clinically used in cancer patients.
Paleo–climatic and paleo–environment implication of clay mineral across Upper Cretaceous–Lower Eocene deposits from Gafsa Basin
Authors: Messadi Abdel Majid
Published: May 2022

An integrated study of clay paragenesis has been conducted in the Gafsa Basin, southern Tunisia, during the Late Cretaceous–Lower Eocene. Six lithostratigraphic sections were logged in the Tamerza, Oued Thelja, Ong, and Chamsi. The Upper Maastrichtian Haria Formation is dominated by smectite, indicating a semi-arid climate with distinct seasons. A colder and drier climate, favoring physical alteration, is observed in the first Paleogene deposits. Danian deposits, show a decrease in smectite in favor of illite and kaolinite, indicating a period of intensified detritus under a hot and humid climate with a contrasting season. The abundance of smectite and the low percentages of kaolinite in the Thelja (Thanetian) Formation suggest a warm and arid climate. The late Thanetian–early Eocene deposits were influenced by a warm and seasonal climate, or probably, they were an alternation between dry and humid seasons and warm climatic conditions in the Lower Eocene corresponding to the Late Paleocene–early Eocene deposits outlining the Paleocene–Eocene Thermal Maximum (PETM). The consequence of this warm climate is sea level rise, which corresponds to the Paleocene– Eocene transgression.
Effect of high-dose cyclophosphamide on ultrastructural changes and gene expression profiles in cardiomyocytes of C57BL/6J mice
Authors: Nishikawa Takuro , Miyahara Emiko , Yamazaki Ieharu , Hagiwara Hiroko , Ikawa Kazuro , Nakagawa Shunsuke , Kodama Yuichi , Kawano Yoshifumi , Okamoto Yasuhiro
Published: May 2022

The pathogenesis of cyclophosphamide (CY)-induced cardiotoxicity remains unknown, and methods for its prevention have not been established. To elucidate acute structural changes in myocardial cells and pathways leading to myocardial damage in mice treated with high-dose CY, we performed detailed pathological analyses of myocardial tissue obtained from C57BL/6J mice that received high-dose CY. In addition, we analyzed the genome-wide cardiomyocyte expression profile of mice that received high-dose CY. Treatment with CY caused marked ultrastructural aberrations with electron microscopy, although these could not be observed with optical microscopy. Expansion of the transverse tubule and sarcoplasmic reticulum, turbulence of myocardial fiber travel, and low contractile protein density in cardiomyocytes were observed. High-dose CY treatment changed cardiomyocyte expression of 1,210 genes associated with cell-cell junctions, inflammatory responses, cardiomyopathy, and cardiac muscle function, as detected by microarray analysis (│Z-score│ > 2.0). The expression of functionally important genes related to myocardial contraction and the regulation of calcium ions was validated using real-time polymerase chain reaction analysis. Our results of gene expression profiles, functional annotation clustering, and the Kyoto Encyclopedia of Genes and Genomes pathway functional classification analysis suggest that cardiotoxicity induced by CY is associated with a disruption of the Ca2+ signaling pathway.
Facial nerve monitoring in parotid gland surgery: Design and feasibility assessment of a potential standardized technique
Authors: Duque Carlos S , Londoño Andres F , Duque Ana M , Zuleta John J , Marulanda Marcela , Otalvaro Lina M , Agudelo Miguel , Dueñas Juan P , Palacio Maria F , Dionigi Gianlorenzo
Published: May 2022

Introduction Even though the use of nerve monitoring during parotid gland surgery is not the gold standard to prevent damage to the nerve, it surely offers some advantages over the traditional approach. Different from thyroid surgery, where a series of steps in intraoperative nerve monitoring have been described in order to confirm not only the integrity but – most importantly – the function of the recurrent laryngeal nerve, in parotid gland surgery, a formal guideline to follow while dissecting the facial nerve has yet to be described.Methods A five-year retrospective study was done reviewing the intraoperative records of patients who underwent parotid gland surgery under neural monitoring. The operative findings regarding the neuromonitoring process, particularly in regard to the amplitude of two main branches, were revised. A literature search was done in order to search for guidelines to follow when a facial nerve loss of signal is encountered.ResultsFifty-six patients were operated on using the Nim 3 Nerve Monitoring System (Medtronic, Jacksonville, FL USA); thirty-three were female patients, 46 patients had benign lesions. Minimum changes were observed in the amplitude records after a comparison was made between the first and the last stimulation. There were only three articles discussing the term loss of signal during parotid gland surgery.ConclusionToday, no sufficient attention has been given to facial nerve monitoring process during parotidectomy. This study proposes and discusses a formal guideline to follow during this procedure in order to develop a uniform technique of facial nerve stimulation.
Cenozoic igneous activity in Northern China as a mechanism for late Oligocene climate warming
Authors: Tao Ze , He Zhiliang , Alves Tiago , Guo Xiaowen , He Sheng , Han Yuanjia
Published: May 2022

Continental rifting is often associated with important magmatism, which significantly influences the Earth’s climate. In this study, we use comprehensive of 3D seismic and borehole datasets from Northern China to document magma intrusion and associated hydrothermal vent complexes (HTVCs) during the Cenozoic. The aim is to understand their impact on late Oligocene - early Miocene climate. Both Mesozoic and Cenozoic magma intrusions occurred in the Bohai Bay Basin, Northern China, while Cenozoic magmatism in the Bohai Bay Basin occurred during late-Oligocene to early-Miocene, when the final stage of rifting occurred in the region. Methane produced by Cenozoic magma in the Boxing Sag alone is estimated to be 27.2-820 Gt, which accounts for approximately 3-5% of the total methane produced in Northern China (1760-21100 Gt). Our study suggests that warm climate during late Oligocene was potentially subjected to intensive rifting related sill emplacements in basins such as the Bohai Bay Basin. Giving the extensively developed Cenozoic magmatic intrusions in the Bohai Bay Basin, our results suggest that, similarly to the Paleocene-Eocene thermal maximum (PETM), igneous activity during late-Oligocene might played a significant role in driving the Late Oligocene Warming event.
Neuroprotective action of α-Klotho against LPS- activated glia conditioned medium in primary neuronal culture
Authors: Nakao Vinicius Wanatable , Mazucanti Caio Henrique Yokowama , Lima Larissa Sá , Mello Paloma Segura , Souza Natacha Medeiros , Kinoshita Paula Fernanda , Leite Jacqueline Alves , Kawamoto Elisa Mitiko , Scavone Cristoforo
Published: May 2022

The α-Klotho is an anti-aging protein that when overexpressed extends the life span in humans and mice. It has an anti-inflammatory and protective action on renal cells by inhibiting NF-κB activation and production of inflammatory cytokines in response to TNF-α. Furthermore, studies have shown the neuroprotective effect of α-Klotho against neuroinflammation on different conditions, such as aging, animal models of neurodegenerative diseases, and ischemic brain injury. This work aimed to evaluate the effects of α-Klotho protein on primary glial cell culture against the proinflammatory challenge with LPS and how this could interfere in neuronal health. Cortical mixed glial cells and purified astrocytes were pretreated with α- α-Klotho and stimulated with LPS followed by TNFα, IL-1β, IL-6, IFN-γ levels and NF-κB activity analysis. Conditioned medium from cortical mixed glia culture treated with LPS (glia conditioned medium (GCM) was used to induce neuronal death of primary cortical neuronal culture and evaluate if GCM-KL (GCM-KL: medium from glia culture pretreated with α- α-Klotho followed by LPS stimulation) can reverse this effect. LPS treatment in glial cells induced an increase in proinflammatory mediators such as TNF-α, IL-1β, IL-6, and IFN-γ, and activation of astrocyte NF-κB. GCM treated-cortical neuronal culture induced a concentration-dependent neuronal death. Pretreatment with α-Klotho decreased TNF-α and IL-6 production, revert NF-κB activation and blocked neuronal death induced by GCM. These data suggest an anti-inflammatory and neuroprotective effect of α-Klotho protein in the CNS. This work demonstrated the therapeutic potential of α-Klotho in pathological processes which involves a neuroinflammatory component.