bluuebunny/crossref_metadata_2025 huggingface dataset:
Case Report: Re-Treatment With Lu-DOTATATE in Neuroendocrine Tumors
Authors: Vida Navas Elena María , Martínez Lorca Alberto , Sancho Gutiérrez Aintzane , Sanz Gómez Lucia , Navarro Martínez Teresa , Grande Pulido Enrique , Carrato Mena Alfredo , Gajate Borau Pablo
Published: April 2021

Peptide receptor radionuclide therapy (PRRT) is an established treatment in advanced neuroendocrine tumors (NETs), which overexpressed somatostatin receptors. However, after progression there are a limited number of available treatments. We want to share a case report about a patient with a NET re-treated with 177Lu-DOTATATE and a literature review about salvage treatment with PRRT. We present a 26-year-old man who started with pelvic pain and after a biopsy of a retro-rectal mass observed in a magnetic resonance was diagnosed with an advanced neuroendocrine tumour. After progression to lanreotide, everolimus and sunitinib, treatment with 177Lu-DOTATATE was initiated, achieving an excellent response with a progression free survival (PFS) of 38 months. At the time of progression, re-treatment with 177Lu-DOTATATE was decided, showing a new partial response, which is currently stable after 15 months. The patient had not presented significant treatment-related toxicity. Although there are no randomized phase III trials or a consensus about the number or dose of cycles, there is evidence about the efficacy and low toxicity of salvage treatment with 177Lu-DOTATATE in NETs. Median progression-free survival ranges from 6 to 22 months. Toxicity is mostly hematologic (anemia and neutropenia), 4-7% grade 3/4.
Digenic Inheritance and Gene-Environment Interaction in a Patient With Hypertriglyceridemia and Acute Pancreatitis
Authors: Yang Qi , Pu Na , Li Xiao-Yao , Shi Xiao-Lei , Chen Wei-Wei , Zhang Guo-Fu , Hu Yue-Peng , Zhou Jing , Chen Fa-Xi , Li Bai-Qiang , Tong Zhi-Hui , Férec Claude , Cooper David N. , Chen Jian-Min , Li Wei-Qin
Published: April 2021

The etiology of hypertriglyceridemia (HTG) and acute pancreatitis (AP) is complex. Herein, we dissected the underlying etiology in a patient with HTG and AP. The patient had a 20-year history of heavy alcohol consumption and an 8-year history of mild HTG. He was hospitalized for alcohol-triggered AP, with a plasma triglyceride (TG) level up to 21.4 mmol/L. A temporary rise in post-heparin LPL concentration (1.5–2.5 times of controls) was noted during the early days of AP whilst LPL activity was consistently low (50∼70% of controls). His TG level rapidly decreased to normal in response to treatment, and remained normal to borderline high during a ∼3-year follow-up period during which he had abstained completely from alcohol. Sequencing of the five primary HTG genes (i.e., LPL, APOC2, APOA5, GPIHBP1 and LMF1) identified two heterozygous variants. One was the common APOA5 c.553G > T (p.Gly185Cys) variant, which has been previously associated with altered TG levels as well as HTG-induced acute pancreatitis (HTG-AP). The other was a rare variant in the LPL gene, c.756T > G (p.Ile252Met), which was predicted to be likely pathogenic and found experimentally to cause a 40% loss of LPL activity without affecting either protein synthesis or secretion. We provide evidence that both a gene-gene interaction (between the common APOA5 variant and the rare LPL variant) and a gene-environment interaction (between alcohol and digenic inheritance) might have contributed to the development of mild HTG and alcohol-triggered AP in the patient, thereby improving our understanding of the complex etiology of HTG and HTG-AP.
Case Report: Splenic Irradiation for the Treatment of Chronic Active Antibody-Mediated Rejection in Kidney Allograft Recipients With De Novo Donor-Specific Antibodies
Authors: Zhu Lan , Guo Zhiliang , Sa Rula , Guo Hui , Li Junhua , Chen Gang
Published: April 2021

Chronic active antibody-mediated rejection (AMR) in renal transplantation is usually refractory to current conventional treatment with rituximab, plasmapheresis (PP), and intravenous immunoglobulins (IVIG). Splenic irradiation has been reported to be effective in the rescue of early severe acute AMR after kidney transplantation; however, its effect in chronic active AMR has not been reported to date. In order to reduce donor-specific antibody (DSA) and prevent the progression of chronic AMR, we used repetitive low-dose splenic irradiation, together with rituximab and PP/IVIG, in two living-related kidney transplant recipients with pathologically diagnosed chronic active AMR and the presence of long-term class II-de novo DSA. DSA monitoring and repeated renal biopsy revealed significantly reduced DSA levels as well as alleviated glomerulitis and peritubular capillaritis in both patients after treatment, and these therapies may have played a role in delaying the progression of chronic AMR. Although DSA levels in both patients eventually rebounded to some extent after treatment, serum creatinine increased slowly in one patient during the 16-month follow-up period and remained stable in the other during the 12-month follow-up period. Given the poor efficacy of conventional treatment at present, splenic irradiation may still be one of the treatment options for chronic active AMR.
Multidrug-Resistant (MDR) Klebsiella variicola Strains Isolated in a Brazilian Hospital Belong to New Clones
Authors: Campos Tatiana Amabile de , Almeida Felipe Marques de , Almeida Ana Paula Cardoso de , Nakamura-Silva Rafael , Oliveira-Silva Mariana , Sousa Isabela Felix Alencar de , Cerdeira Louise , Lincopan Nilton , Pappas Georgios Joannis , Pitondo-Silva André
Published: April 2021

Klebsiella variicola is mainly associated with opportunistic infections and frequently identified as Klebsiella pneumoniae. This misidentification implies a wrong epidemiology result as well as incorrect attribution to K. pneumoniae as the etiology of some severe infections. Recently, huge efforts have been made to study K. variicola, however, the biological aspects of this species are still unclear. Here we characterized five K. variicola strains initially identified as K. pneumoniae, with a Vitek-2 System and 16S rRNA sequencing. One-step multiplex polymerase chain reaction and Whole Genome Sequencing (WGS) identified them as K. variicola. Additionally, WGS analysis showed that all the strains are closely related with K. variicola genomes, forming a clustered group, apart from K. pneumoniae and K. quasipneumoniae. Multilocus sequence typing analysis showed four different sequence types (STs) among the strains and for two of them (Kv97 and Kv104) the same ST was assigned. All strains were multidrug-resistant (MDR) and three showed virulence phenotypes including invasion capacity to epithelial cells, and survival in human blood and serum. These results showed the emergence of new K. variicola clones with pathogenic potential to colonize and cause infection in different tissues. These characteristics associated with MDR strains raise great concern for human health.
circATP2B1 Promotes Aerobic Glycolysis in Gastric Cancer Cells Through Regulation of the miR-326 Gene Cluster
Authors: Zhao Xihe , Tian Zhong , Liu Lei
Published: April 2021

The discovery of circular RNA (circRNA) enormously complimented the repertoire of traditional gene expression theory. As a type of endogenous noncoding RNA, circRNA participates in the occurrence of many kinds of tumors in addition to regulating their development. The Warburg effect (aerobic glycolysis is taken with priority for cancer cells instead of oxidative phosphorylation) is one of the most important factors involved in the excessive proliferation of gastric cancer cells. Our data showed that circRNA circATP2B1 (also called hsa_circ_000826) was overexpressed in gastric cancer tissues instead of linear ATP2B1 mRNA, and it promoted aerobic glycolysis in gastric cancer cells. Bioinformatic Gene Ontology analysis showed that the potential downstream targets of circATP2B1 include the microRNA miR-326 gene cluster (miR-326-3p/miR-330-5p), which is functionally focused on cell growth and metabolic processes. The expressions of miR-326-3p/miR-330-5p were downregulated in gastric cancer, and circATP2B1 functionally targeted miR-326-3p/miR-330-5p in an RNA-induced silencing complex (RISC) dependent manner. Dual-luciferase reporter assays demonstrated that pyruvate kinase M2 (PKM2) was one of the targets of miR-326-3p/miR-330-5p. As a rate-limiting enzyme in the aerobic glycolytic pathway, PKM2 accelerated gastric cancer cells’ glucose uptake and increased cell viability. Taken together, circATP2B1 captured miR-326-3p/miR-330-5p and decreased the suppression of PKM2 by miR-326-3p/miR-330-5p, thus aiding the aerobic glycolysis and proliferation of gastric cancer cells. This study identified a novel molecular pathway in gastric cancer that may provide more targets for reversing cancer metabolic reprogramming, as well as a potential strategy for targeted therapy of gastric cancer.
Targeting ADT-Induced Activation of the E3 Ubiquitin Ligase Siah2 to Delay the Occurrence of Castration-Resistant Prostate Cancer
Authors: Yan Tingmang , Zhou Dapeng , Shi Youwei , Cui Di , Jiang Juntao , Han Bangmin , Xia Shujie , Wang Zhou , Liu Haitao , Guo Wenhuan , Jing Yifeng
Published: April 2021

Siah2 is an E3 ubiquitin ligase that targets androgen receptor (AR) and plays an important role in the development of castration-resistant prostate cancer (CRPC). However, the regulation of Siah2 in prostate cancer (PCa) is largely unknown. In this study, we used AR-dependent and -independent cells lines to investigate the cellular roles of AR and androgen deprivation therapy (ADT) on Siah2 protein levels and E3 ligase activity using Western blotting and co-immunoprecipitation. We also validated our findings using patient samples taken before and after ADT. Finally, we used xenograft tumor models to test the effects of ADT combined with vitamin K3 (Vit K3) on tumor growth in vivo. Our results showed that AR stabilizes Siah2 protein by attenuating its self-ubiquitination and auto-degradation, likely by blocking its E3 ubiquitin ligase activity. Conversely, ADT decreased Siah2 protein expression but enhanced its E3 ligase activity in PCa cells. Notably, the findings that ADT decreasing Siah2 protein expression were verified in a series of paired PCa samples from the same patient. Additionally, we found that ADT-induced Siah2 activation could be abolished by Vit K3. Strikingly, ADT combined with Vit K3 treatment delayed the occurrence of CRPC and dramatically inhibited the growth of tumor xenografts compared with ADT treatment alone. AR is an inhibitor of Siah2 in PCa, and ADT leads to the continuous activation of Siah2, which may contribute to CRPC. Finally, ADT+Vit K3 may be a potential approach to delay the occurrence of CRPC.
Transvesical Versus Posterior Approach to Retzius-Sparing Robot-Assisted Radical Prostatectomy: A Retrospective Comparison With a 12-Month Follow-Up
Authors: Deng Wen , Zhang Cheng , Jiang Hao , Li Yulei , Zhu Ke , Liu Xiaoqiang , Chen Luyao , Liu Weipeng , Guo Ju , Zhou Xiaochen , Fu Bin , Wang Gongxian
Published: April 2021

Objectives

To assess the perioperative, functional, and oncological outcomes of transvesical robot-assisted radical prostatectomy (T-RARP) and posterior robot-assisted radical prostatectomy (P-RARP) for localized prostate cancer.

Materials and Methods

We analyzed the data of 96 patients who underwent T-RARP or P-RARP for localized prostate cancer between January 2017 and June 2019 in a retrospective fashion.

Results

No significant differences in the baseline characteristics existed between the T-RARP and P-RARP arms. Both interventions were successfully performed without open conversion in either group. T-RARP was associated with a slightly more operative time (135.3 vs. 127.3 min) and estimated blood loss (105.2 vs. 94.2 mL) than P-RARP, but the differences were not significant (both p > 0.05). The likelihood of transfusion, ≤Grade II, and >Grade II postoperative complications, pT3a disease and positive surgical margins in the T-RARP group was comparable with that in the P-RARP group. No significant differences were noted between these two arms in terms of UC at the removal of catheter and nocturia (p = 0.750 and p = 0.684, respectively), and all included patients recovered UC at 3 months postoperatively. The median International Index of Erectile Function-5 score in both groups remains comparable before and after RARP. The patients in the T-RARP and P-RARP groups had a similar biochemical recurrence-free survival (p = 0.387).

Conclusions

Both T-RARP and P-RARP by experienced hands are feasible for well-selected patients with prostate cancer, obtaining similar outcomes in terms of perioperative results, UC and erectile function, and oncological control within short-term follow-up.
The Relevance of Assessing Subjective Experiences of Skin Toxicity During Adjuvant Radiotherapy for Breast Cancer
Authors: Bottesi Gioia , Stefanelli Antonio , Ambroso Giovanni , Baratto Gianni , Carraro Eleonora , Cristaudo Agostino , Giuntoli Laura , Maramaldi Giada , Meneghin Martino , Pozzati Genny , Semenzato Alessandra , Togni Stefano , Vidotto Giulio
Published: April 2021

Purpose

Radiodermatitis is likely to be an inevitable side effect of radiotherapy (RT) but experiencing pain relief during RT might contribute making treatment more acceptable and less impairing. The current study aimed to assess the subjective perceptions and experiences of skin toxicity in a sample of women undergoing adjuvant RT for breast cancer.

Methods

Eighty patients were randomly assigned to one out of two groups: treatment (i.e., a newly developed topical product) and control (i.e., standard-of-care). Patients underwent adjuvant RT for 3 weeks. Clinical assessment of radiodermatitis and self-reported levels of pain, relief, and perceptions of treatment response were collected at the initiation of RT (T1), during RT (T2 and T3), and 2 weeks after treatment completion (T4). To assess changes in skin-related QoL, a subgroup of patients completed the Padua Skin-Related QoL questionnaire at T0 (before the initiation of RT) and at T4.

Results

A comparable timing of onset and severity of radiodermatitis during treatment was observed in both groups. The treatment group reported lower levels of pain and higher levels of relief compared to the control group when skin toxicity was at its highest levels (T2 and T3). Independent of the group, levels of perceived improvements in clinical status increased over time, whereas skin-related QoL worsened from T0 to T4.

Conclusion

Current findings outline the relevance of integrating clinical evaluations of radiodermatitis with patients’ subjective experiences of skin toxicity in interventional studies. Moreover, they provide preliminary evidence about the soothing effect of a newly developed topical product, thus supporting its usefulness of as a supportive care.
Prediction of the Growth Rate of Early-Stage Lung Adenocarcinoma by Radiomics
Authors: Tan Mingyu , Ma Weiling , Sun Yingli , Gao Pan , Huang Xuemei , Lu Jinjuan , Chen Wufei , Wu Yue , Jin Liang , Tang Lin , Kuang Kaiming , Li Ming
Published: April 2021

Objectives

To investigate the value of imaging in predicting the growth rate of early lung adenocarcinoma.

Methods

From January 2012 to June 2018, 402 patients with pathology-confirmed lung adenocarcinoma who had two or more thin-layer CT follow-up images were retrospectively analyzed, involving 407 nodules. Two complete preoperative CT images and complete clinical data were evaluated. Training and validation sets were randomly assigned according to an 8:2 ratio. All cases were divided into fast-growing and slow-growing groups. Researchers extracted 1218 radiomics features from each volumetric region of interest (VOI). Then, radiomics features were selected by repeatability analysis and Analysis of Variance (ANOVA); Based on the Univariate and multivariate analyses, the significant radiographic features is selected in training set. A decision tree algorithm was conducted to establish the radiographic model, radiomics model and the combined radiographic-radiomics model. Model performance was assessed by the area under the curve (AUC) obtained by receiver operating characteristic (ROC) analysis.

Results

Sixty-two radiomics features and one radiographic features were selected for predicting the growth rate of pulmonary nodules. The combined radiographic-radiomics model (AUC 0.78) performed better than the radiographic model (0.727) and the radiomics model (0.710) in the validation set.

Conclusions

The model has good clinical application value and development prospects to predict the growth rate of early lung adenocarcinoma through the combined radiographic-radiomics model.
New Trends in Pharmacological Treatments for Osteoarthritis
Authors: Cai Xiaoyan , Yuan Shiwen , Zeng Yanting , Wang Cuicui , Yu Na , Ding Changhai
Published: April 2021

Osteoarthritis (OA) is the leading cause of function loss and disability among the elderly, with significant burden on the individual and society. It is a severe disease for its high disability rates, morbidity, costs, and increased mortality. Multifactorial etiologies contribute to the occurrence and development of OA. The heterogeneous condition poses a challenge for the development of effective treatment for OA; however, emerging treatments are promising to bring benefits for OA management in the future. This narrative review will discuss recent developments of agents for the treatment of OA, including potential disease-modifying osteoarthritis drugs (DMOADs) and novel therapeutics for pain relief. This review will focus more on drugs that have been in clinical trials, as well as attractive drugs with potential applications in preclinical research. In the past few years, it has been realized that a complex interaction of multifactorial mechanisms is involved in the pathophysiology of OA. The authors believe there is no miracle therapeutic strategy fitting for all patients. OA phenotyping would be helpful for therapy selection. A variety of potential therapeutics targeting inflammation mechanisms, cellular senescence, cartilage metabolism, subchondral bone remodeling, and the peripheral nociceptive pathways are expected to reshape the landscape of OA treatment over the next few years. Precise randomized controlled trials (RCTs) are expected to identify the safety and efficacy of novel therapies targeting specific mechanisms in OA patients with specific phenotypes.
Building Evidence for Pre-school Policy Change in Bulgaria
Authors: Volen Eugenia , de Laat Joost
Published: April 2021

In September 2020, Bulgaria's National Assembly (Parliament) passed legal amendments aimed at increasing kindergarten participation for children aged 4–6 in Bulgaria, with poor children standing to benefit the most. For the first time, state budget funds were set aside to relieve parents of the costs of monthly attendance fees currently collected by full-day kindergartens. It builds on evidence generated from a large-scale randomized control trial (RCT) (2014–2018) across 236 poor communities, implemented by the Trust for Social Achievement (TSA) together with the World Bank and the Abdul Latif Jameel Poverty Action Lab. This paper describes how the RCT was used by TSA to advocate for removal of fees, and how much more evidence besides the RCT needed to be generated and support needed to be mobilized to influence policy action.
What About the Environment? How the Physical Activity–Related Health Competence Model Can Benefit From Health Literacy Research
Authors: Carl Johannes , Grüne Eva , Pfeifer Klaus
Published: April 2021

Research cultivates a multitude of frameworks, models, and theories with different determinants internal and/or external to the individual contributing to the understanding and explaining of physical activity levels. The physical activity–related health competence (PAHCO) model can be located at the interface between research of health literacy and physical activity. Because of its primary person orientation, however, the model has not yet undergone discussions on the relevance of the environment. Encouraged by the developments in the area of health literacy, the goal of the present perspective article was to stimulate some initial reflections on potential solutions for the competence–environment relationship within the PAHCO model. We extracted three potential solutions for this issue. Dubbed the solution of integration, we first discussed that the PAHCO model could be placed into overarching, more holistic, and abstract models of health-enhancing physical activity, such as the capability approach or the socioecological model. Applying a solution of elaboration, researchers could second substantiate existing components of the PAHCO model, such as control competence or self-regulation competence, by further explanations. Characterizing the solution of extension, it would third be possible to introduce (a) separate competence component(s) that highlight(s) the manageability of the environment, for instance, by establishing a (socio)ecological competence. The article concludes with a short overview of potential empirical approaches, given their potential to assist researchers in identifying preferences for the theoretical advancement and to put the development on a stronger evidence base.
Alley Cropping Mitigates the Impacts of Climate Change on a Wheat Crop in a Mediterranean Environment: A Biophysical Model-Based Assessment
Authors: Reyes Francesco , Gosme Marie , Wolz Kevin J. , Lecomte Isabelle , Dupraz Christian
Published: April 2021

Introduction: Climate change (CC) and the increased occurrence of extreme climatic events pose a serious threat to crop yields and their stability worldwide. This study analyzed the CC mitigation potential of an alley cropping system on crop physiological stresses and growth as compared to a monoculture system. Materials and Methods: Growth of winter durum wheat, cultivated alone (agriculture) and in combination with hybrid walnut (agroforestry), was simulated with the Hi-sAFe agroforestry model, as driven by business-as-usual Intergovernmental Panel on Climate Change (IPCC) projections, split into three scenarios, representing Past (1951–1990), Present (1991–2030), and Future (2031–2070) climatic conditions. Crop growth and the occurrence of thermal, nitrogen, and water stresses were analyzed. Results: Cold-related stresses were modest in Past and almost disappeared over time. Heat, drought, and nitrogen stresses increased about twofold from Past to Future, but were reduced by 20–35% in agroforestry, already with medium-sized trees (diameter at breast height (DBH) of about 10–15 cm). Crop yields in agriculture increased from Past to the end of Present and then remained stable. This moderately decreased with tree age in agroforestry (especially in Future). Discussion: The impact of CC on the crop was buffered in agroforestry, especially for the most extreme climatic events. The mitigation of crop microclimate and the increased stability of crop yields highlight the potential of agroforestry as a CC adaptation strategy.
China’s Tea Industry: Net Greenhouse Gas Emissions and Mitigation Potential
Authors: Liang Long , Ridoutt Bradley G. , Wang Liyuan , Xie Bin , Li Minghong , Li Zhongbai
Published: April 2021

Tea is an important cash crop and a beverage that is widely consumed across the world. In China (the largest producer of tea), the industry is growing, and there is a need to understand current greenhouse gas (GHG) emissions and sequestrations and the potential for mitigation so that climate action can be strategically undertaken. Life cycle assessment and carbon footprint methods were used to quantify emissions in tea cultivation and processing in the 16 major producing regions for the year 2017. The system boundary was from cradle to factory gate, which was divided into three subsystems, namely agricultural materials production, tea production and tea processing. Several units of analysis were chosen: the production region (province), the production area (ha) and the product (kg loose tea), etc. Total GHG emissions were 28.75 Mt CO2eq, which were mainly attributable to energy use in tea processing (41%), fertilizer production (31.6%) and soil emissions (26.7%). This equated to 12.0 t CO2eq per ha and 10.8 kg CO2eq per kg processed tea. Production in Hubei, Yunan, Guizhou, Sichuan and Fujian provinces contributed almost two thirds of industry emissions, representing priority areas for strategic action to reduce GHG emissions. At the same time, the total carbon sink amounted to 21.37 MtCO2, representing 74.3% of total GHG emissions. The proportions stored in soil, biomass, and tea production were 49.3%, 30.0%, and 20.7%, respectively. If best recommended management practices for fertilizer application were adopted and biomass was used as a source of energy for tea processing, the GHG emissions reduction potential was 16.66 Mt CO2eq, or 58% of total emissions. The GHG emissions associated with tea production and processing in China appeared high by comparison to other regions of the world. However, considering the carbon sink and emissions reduction potential, the tea industry should be viewed as an important sector for climate action. Moreover, the potential for substantial GHG emissions reduction through the adoption of improved practices seems very realistic. There may also be additional opportunities for GHG emissions reduction through the development of organic tea cultivation systems.
Compost Tea Induces Growth and Resistance against Rhizoctonia solani and Phytophthora capsici in Pepper
Authors: González-Hernández Ana Isabel , Suárez-Fernández M. Belén , Pérez-Sánchez Rodrigo , Gómez-Sánchez María Ángeles , Morales-Corts María Remedios
Published: April 2021

Compost teas (CTs) are organic solutions that constitute an interesting option for sustainable agriculture. Those that come from garden waste have been applied in vitro and in vivo on pepper plants to determine its suppressive effect against both Phytophthora capsici and Rhizoctonia solani. The studied CT showed relevant content in NO3−, K2O, humic acids, and microorganisms such as aerobic bacteria, N-fixing bacteria, and actinobacteria, which play a role in plant growth and resistance. This rich abundance of microbiota in the CT induced a reduction in the relative growth rate of both P. capsici and R. solani (31.7% and 38.0%, respectively) in in vitro assays compared to control. In addition, CT-irrigated plants displayed increased growth parameters and showed the first open flower one week before those treatments without CTs, which suggests that its application advanced the crop cycle. Concerning pathogen infection, damage caused by both pathogens became more apparent with a one-week inoculation compared to a four-week inoculation, which may indicate that a microbiological and chemical balance had been reached to cope with biotic stresses. Based on these results, we conclude that CT application induces plant growth and defense in pepper plants against P. capsici and R. solani because of its relevant soluble nutrient content and microbiota richness, which provides a novel point for plant nutrition and protection in horticultural crops.
Is Domestication Speciation? The Implications of a Messy Domestication Model in the Holocene
Authors: Bates Jennifer
Published: April 2021

Domestication is one of the fundamental process that has shaped our world in the last 12,000 years. Changes in the morphology, genetics, and behavior of plants and animals have redefined our interactions with our environments and ourselves. However, while great strides have been made towards understanding the mechanics, timing, and localities of domestication, a fundamental question remains at the heart of archaeological and scientific modelling of this process—how does domestication fit into a framework of evolution and natural selection? At the core of this is the ontological problem of what is a species? In this paper, the complicated concepts and constructs underlying ‘species’ and how this can be applied to the process of domestication are explored. The case studies of soybean and proto-indica rice are used to illustrate that our choice of ‘species’ definitions carries with it ramifications for our interpretations, and that care needs to be made when handling this challenging classificatory system.
Predicting the Lime Demand of Arable Soils from pH Value, Soil Texture and Soil Organic Matter Content
Authors: Ruehlmann Joerg , Bönecke Eric , Meyer Swen
Published: April 2021

For more than 40 years, farmers in Germany have used the fertilization recommendation schema provided by the Association of German Agricultural Investigation and Research Institutions (VDLUFA) to quantify the required lime (CaO) demand of arable mineral soils. To be applicable as guidelines in practice, the results of 30 years of fertilization experiments that studied the correlation between crop yields and the actual soil pH, the soil texture, and the soil organic matter (SOM) content were finally condensed into a look-up table system. However, because the original experimental data are no longer accessible, the purpose of this study is to reconstruct the interaction between the three soil parameters and their appropriate lime demands. Therefore, the class-based, stepwise approach of the look-up table system is transferred into a continuous, stepless approach using mathematical models. Under the precondition to preserve the pH-, texture- and SOM-dependent CaO amounts recommended in the look-up system (n = 317) to the greatest extent possible, the algorithm was successful; more than 99% of their variability could be explained by the models. This adaptation helps to meet the accuracy of present-day requirements of precision farming.
Effect of White Clover (Trifolium repens L.) Undersowing Cultivation and Nitrogen Fertilization on Weed Infestation, Biomass Yield and Its Component, Content and Uptake of Macroelements of Willow (Salix viminalis L.)
Authors: Helios Waldemar
Published: April 2021

Fertilization of willow with nitrogen is an important issue with economic and environmental implications. The study was aimed at determining the effect of nitrogen fertilization and white clover on weed infestation, morphology, biomass and chemical composition of willow. A field experiment was established at Wroclaw University of Environmental and Life Sciences (Poland) during the years 2013–2017 with the use of a randomized complete block design (RCBD). The results showed that the number and dry mass of weeds per m2, the number of willow shoots and the fresh weight yield of willow were smaller where the clover was sown. The plants were found to be higher after applying nitrogen fertilization. The dry mass yield and shoot diameter did not depend on the cultivation method. Nitrogen fertilization increased the ash content. Undersowing willow with white clover, higher nitrogen content was found. Nitrogen fertilization increased the content of ash, and in undersowing cultivation, the willow stems had higher nitrogen content than in monoculture. On average, the phloem had 5.6 times higher crude ash content and 4.6 times higher nitrogen content than wood. On the basis of the conducted research, it can be concluded that in the first years after planting, the undersowing growing of willow with white clover can be an alternative to plantations fertilized and non-fertilized with nitrogen.
Prevalence of and Factors Associated with Antibiotic Prescriptions in Patients with Acute Lower and Upper Respiratory Tract Infections—A Case-Control Study
Authors: Kern Winfried V. , Kostev Karel
Published: April 2021

Background: The goal of the present study was to estimate the prevalence of patient and physician related variables associated with antibiotic prescriptions in patients diagnosed with acute lower and upper respiratory tract infections (ALURTI), treated in general practices (GP) and pediatric practices, in Germany. Methods: The analysis included 1,140,095 adult individuals in 1237 general practices and 309,059 children and adolescents in 236 pediatric practices, from the Disease Analyzer database (IQVIA), who had received at least one diagnosis of an ALURTI between 1 January 2015 and 31 March 2019. We estimated the association between 35 predefined variables and antibiotic prescription using multivariate logistic regression models, separately for general and pediatric practices. The variables included the proportion (as a percentage) of antibiotics or phytopharmaceuticals on all prescriptions per practice, as an indicator of physician prescription preference. Results: The prevalence of antibiotic prescription was higher in patients treated in GP (31.2%) than in pediatric practices (9.1%). In GP, the strongest association with antibiotic prescription was seen in the practice preference for antibiotic use, followed by specific diagnoses (acute bronchitis, sinusitis, pharyngitis, laryngitis, and tracheitis), and higher patient age. In pediatric practices, acute sinusitis and bronchitis were the variables with the strongest association, followed by practice preference for antibiotic prescription. The strongest association with the non-prescription of antibiotics was practice preference for phytopharmaceuticals and the specific diagnosis of a viral infection. Conclusion: This study shows a high prevalence of antibiotic prescribing for patients with ALURTI in a primary care setting, especially in adult patients; physician related factors play an important role that should be addressed in interventions to reduce potentially inappropriate antibiotic prescribing.
Catalase Modulates the Radio-Sensitization of Pancreatic Cancer Cells by Pharmacological Ascorbate
Authors: Du Juan , Carroll Rory S. , Steers Garett J. , Wagner Brett A. , O’Leary Brianne R. , Jensen Chris S. , Buettner Garry R. , Cullen Joseph J.
Published: April 2021

Pancreatic cancer cells (PDACs) are more susceptible to an oxidative insult than normal cells, resulting in greater cytotoxicity upon exposure to agents that increase pro-oxidant levels. Pharmacological ascorbate (P-AscH−), i.e., large amounts given intravenously (IV), generates significant fluxes of hydrogen peroxide (H2O2), resulting in the killing of PDACs but not normal cells. Recent studies have demonstrated that P-AscH− radio-sensitizes PDAC but is a radioprotector to normal cells and tissues. Several mechanisms have been hypothesized to explain the dual roles of P-AscH− in radiation-induced toxicity including the activation of nuclear factor-erythroid 2-related factor 2 (Nrf2), RelB, as well as changes in bioenergetic profiles. We have found that P-AscH− in conjunction with radiation increases Nrf2 in both cancer cells and normal cells. Although P-AscH− with radiation decreases RelB in cancer cells vs. normal cells, the knockout of RelB does not radio-sensitize PDACs. Cellular bioenergetic profiles demonstrate that P-AscH− with radiation increases the ATP demand/production rate (glycolytic and oxidative phosphorylation) in both PDACs and normal cells. Knocking out catalase results in P-AscH− radio-sensitization in PDACs. In a phase I trial where P-AscH− was included as an adjuvant to the standard of care, short-term survivors had higher catalase levels in tumor tissue, compared to long-term survivors. These data suggest that P-AscH− radio-sensitizes PDACs through increased peroxide flux. Catalase levels could be a possible indicator for how tumors will respond to P-AscH−.
Curcumin-Loaded Hydrophobic Surface-Modified Hydroxyapatite as an Antioxidant for Sarcopenia Prevention
Authors: Liang Ya-Jyun , Yang I-Hsuan , Lin Yi-Wen , Lin Jhih-Ni , Wu Chang-Chin , Chiang Chih-Yung , Lai Kun-Hung , Lin Feng-Huei
Published: April 2021

Oxidative stress and later-induced chronic inflammation have been reported to play an important role on the progression of sarcopenia. Current treatments for sarcopenia are mainly administered to patients whom sarcopenia already developed. However, there has been no promising results shown in therapy. Therefore, the development of therapeutic and preventive strategies against sarcopenia would be necessary. Curcumin is a traditional medicine that possesses anti-inflammatory and antioxidative properties. In the present study, hydroxyapatite was subjected to hydrophobic surface modifications for curcumin loading (Cur-SHAP). It was, subsequently, utilized for delivery to the patient’s body via intramuscular injection in order to achieve constant release for more than 2 weeks, preventing the progression of the sarcopenia or even leading to recovery from the early stage of the illness. According to the results of WST-1, LIVE/DEAD, DCFDA, and gene expression assays, Cur-SHAP exhibited good biocompatibility and showed great antioxidant/anti-inflammatory effects through the endocytic pathway. The results of the animal studies showed that the muscle endurance, grip strength, and fat/lean mass ratio were all improved in Cur-SHAP-treated rats from LPS-induced sarcopenia. In summary, we successfully synthesized hydrophobic surface modification hydroxyapatite for curcumin loading (Cur-SHAP) and drug delivery via the IM route. The LPS-induced sarcopenia rats were able to recover from disease after the Cur-SHAP treatment.
Travel-Time Inversion Method of Converted Shear Waves Using RayInvr Algorithm
Authors: Wen Genggeng , Wan Kuiyuan , Xia Shaohong , Xu Huilong , Fan Chaoyan , Cao Jinghe
Published: April 2021

The detailed studies of converted S-waves recorded on the Ocean Bottom Seismometer (OBS) can provide evidence for constraining lithology and geophysical properties. However, the research of converted S-waves remains a weakness, especially the S-waves’ inversion. In this study, we applied a travel-time inversion method of converted S-waves to obtain the crustal S-wave velocity along the profile NS5. The velocities of the crust are determined by the following four aspects: (1) modelling the P-wave velocity, (2) constrained sediments Vp/Vs ratios and S-wave velocity using PPS phases, (3) the correction of PSS phases’ travel-time, and (4) appropriate parameters and initial model are selected for inversion. Our results show that the vs. and Vp/Vs of the crust are 3.0–4.4 km/s and 1.71–1.80, respectively. The inversion model has a similar trend in velocity and Vp/Vs ratios with the forward model, due to a small difference with ∆Vs of 0.1 km/s and ∆Vp/Vs of 0.03 between two models. In addition, the high-resolution inversion model has revealed many details of the crustal structures, including magma conduits, which further supports our method as feasible.
Some Plant Food Products Present on the Polish Market Are a Source of Vitamin B12
Authors: Jedut Paulina , Szwajgier Dominik , Glibowski Paweł , Iłowiecka Katarzyna
Published: April 2021

Cyanocobalamin is the most widespread form of vitamin B12, which is sufficient for humans. Vitamin B12 is mainly found in animal products. However, supplementation does not have to be necessary because certain amounts of vitamin B12 are present in plant products. Previous studies showed significant contents of cyanocobalamin in sea buckthorn and in sauerkraut. In this study, selected products such as sea-buckthorn jam and fermented plant products (obtained by lactic acid fermentation) were tested in a search for vitamin B12. Bacteria involved in this type of fermentation have the potential to produce cyanocobalamin. Popular fermented plant products on the Polish market were selected, namely sauerkraut and pickled cucumbers, as well as parsley juice, beetroot juice and white borscht. The analysis was carried out using HPLC-UV. Most of the analyzed products did not contain significant levels of vitamin B12. Only sea-buckthorn jam and pickled parsley juice can provide the amount of vitamin B12 needed to prevent deficiency.
Pressure-Driven Nitrogen Flow in Divergent Microchannels with Isothermal Walls
Authors: Ebrahimi Amin , Shahabi Vahid , Roohi Ehsan
Published: April 2021

Gas flow and heat transfer in confined geometries at micro-and nanoscales differ considerably from those at macro-scales, mainly due to nonequilibrium effects such as velocity slip and temperature jump. Nonequilibrium effects increase with a decrease in the characteristic length-scale of the fluid flow or the gas density, leading to the failure of the standard Navier–Stokes–Fourier (NSF) equations in predicting thermal and fluid flow fields. The direct simulation Monte Carlo (DSMC) method is employed in the present work to investigate pressure-driven nitrogen flow in divergent microchannels with various divergence angles and isothermal walls. The thermal fields obtained from numerical simulations are analysed for different inlet-to-outlet pressure ratios (1.5≤Π≤2.5), tangential momentum accommodation coefficients, and Knudsen numbers (0.05≤Kn≤12.5), covering slip to free-molecular rarefaction regimes. The thermal field in the microchannel is predicted, heat-lines are visualised, and the physics of heat transfer in the microchannel is discussed. Due to the rarefaction effects, the direction of heat flow is largely opposite to that of the mass flow. However, the interplay between thermal and pressure gradients, which are affected by geometrical configurations of the microchannel and the applied boundary conditions, determines the net heat flow direction. Additionally, the occurrence of thermal separation and cold-to-hot heat transfer (also known as anti-Fourier heat transfer) in divergent microchannels is explained.
Reliable and Robust Observer for Simultaneously Estimating State-of-Charge and State-of-Health of LiFePO4 Batteries
Authors: Al-Gabalawy Mostafa , Mahmoud Karar , Darwish Mohamed M.F. , Dawson James A. , Lehtonen Matti , Hosny Nesreen S.
Published: April 2021

Batteries are everywhere, in all forms of transportation, electronics, and constitute a method to store clean energy. Among the diverse types available, the lithium-iron-phosphate (LiFePO4) battery stands out for its common usage in many applications. For the battery’s safe operation, the state of charge (SOC) and state of health (SOH) estimations are essential. Therefore, a reliable and robust observer is proposed in this paper which could estimate the SOC and SOH of LiFePO4 batteries simultaneously with high accuracy rates. For this purpose, a battery model was developed by establishing an equivalent-circuit model with the ambient temperature and the current as inputs, while the measured output was adopted to be the voltage where current and terminal voltage sensors are utilized. Another vital contribution is formulating a comprehensive model that combines three parts: a thermal model, an electrical model, and an aging model. To ensure high accuracy rates of the proposed observer, we adopt the use of the dual extend Kalman filter (DEKF) for the SOC and SOH estimation of LiFePO4 batteries. To test the effectiveness of the proposed observer, various simulations and test cases were performed where the construction of the battery system and the simulation were done using MATLAB. The findings confirm that the best observer was a voltage-temperature (VT) observer, which could observe SOC accurately with great robustness, while an open-loop observer was used to observe the SOH. Furthermore, the robustness of the designed observer was proved by simulating ill-conditions that involve wrong initial estimates and wrong model parameters. The results demonstrate the reliability and robustness of the proposed observer for simultaneously estimating the SOC and SOH of LiFePO4 batteries.
Cation Transporters of Candida albicans—New Targets to Fight Candidiasis?
Authors: Volkova Marina , Atamas Anastasia , Tsarenko Alexey , Rogachev Andrey , Guskov Albert
Published: April 2021

Candidiasis is the wide-spread fungal infection caused by numerous strains of yeast, with the prevalence of Candida albicans. The current treatment of candidiasis is becoming rather ineffective and costly owing to the emergence of resistant strains; hence, the exploration of new possible drug targets is necessary. The most promising route is the development of novel antibiotics targeting this pathogen. In this review, we summarize such candidates found in C. albicans and those involved in the transport of (metal) cations, as the latter are essential for numerous processes within the cell; hence, disruption of their fluxes can be fatal for C. albicans.
Sources of Inaccuracy in Photoplethysmography for Continuous Cardiovascular Monitoring
Authors: Fine Jesse , Branan Kimberly L. , Rodriguez Andres J. , Boonya-ananta Tananant , Ajmal  , Ramella-Roman Jessica C. , McShane Michael J. , Coté Gerard L.
Published: April 2021

Photoplethysmography (PPG) is a low-cost, noninvasive optical technique that uses change in light transmission with changes in blood volume within tissue to provide information for cardiovascular health and fitness. As remote health and wearable medical devices become more prevalent, PPG devices are being developed as part of wearable systems to monitor parameters such as heart rate (HR) that do not require complex analysis of the PPG waveform. However, complex analyses of the PPG waveform yield valuable clinical information, such as: blood pressure, respiratory information, sympathetic nervous system activity, and heart rate variability. Systems aiming to derive such complex parameters do not always account for realistic sources of noise, as testing is performed within controlled parameter spaces. A wearable monitoring tool to be used beyond fitness and heart rate must account for noise sources originating from individual patient variations (e.g., skin tone, obesity, age, and gender), physiology (e.g., respiration, venous pulsation, body site of measurement, and body temperature), and external perturbations of the device itself (e.g., motion artifact, ambient light, and applied pressure to the skin). Here, we present a comprehensive review of the literature that aims to summarize these noise sources for future PPG device development for use in health monitoring.
Role of SHH in Patterning Human Pluripotent Cells towards Ventral Forebrain Fates
Authors: Brady Melanie V. , Vaccarino Flora M.
Published: April 2021

The complexities of human neurodevelopment have historically been challenging to decipher but continue to be of great interest in the contexts of healthy neurobiology and disease. The classic animal models and monolayer in vitro systems have limited the types of questions scientists can strive to answer in addition to the technical ability to answer them. However, the tridimensional human stem cell-derived organoid system provides the unique opportunity to model human development and mimic the diverse cellular composition of human organs. This strategy is adaptable and malleable, and these neural organoids possess the morphogenic sensitivity to be patterned in various ways to generate the different regions of the human brain. Furthermore, recapitulating human development provides a platform for disease modeling. One master regulator of human neurodevelopment in many regions of the human brain is sonic hedgehog (SHH), whose expression gradient and pathway activation are responsible for conferring ventral identity and shaping cellular phenotypes throughout the neural axis. This review first discusses the benefits, challenges, and limitations of using organoids for studying human neurodevelopment and disease, comparing advantages and disadvantages with other in vivo and in vitro model systems. Next, we explore the range of control that SHH exhibits on human neurodevelopment, and the application of SHH to various stem cell methodologies, including organoids, to expand our understanding of human development and disease. We outline how this strategy will eventually bring us much closer to uncovering the intricacies of human neurodevelopment and biology.