bluuebunny/crossref_metadata_2025 huggingface dataset:
Lack of Major Genome-Wide DNA Methylation Changes in Succinate-Treated Human Epithelial Cells
Authors: Cui Wei , Huang Zhijun , Pfeifer Gerd P.
Published: May 2022

The tricarboxylic acid (TCA) metabolite, succinate, is a competitive inhibitor of dioxygenase enzymes that require alpha ketoglutarate as a cofactor. One family of dioxygenases are the ten-eleven translocation (TET) proteins, which oxidize 5-methylcytosine to promote DNA demethylation. Inhibition of DNA demethylation is expected to lead to DNA hypermethylation, at least at genomic regions at which TET proteins are engaged. We treated human bronchial epithelial cells with succinate for five days and confirmed its effect on TET protein function by observing diminished formation of 5-hydroxymethylcytosine, the first oxidation product of the TET enzymatic reaction. We then analyzed global DNA methylation patterns by performing whole-genome bisulfite sequencing. Unexpectedly, we did not observe differentially methylated regions (DMRs) that reached genome-wide statistical significance. We observed a few regions of clustered DNA hypomethylation, which was also not expected based on the proposed mechanisms. We discuss potential explanations for our observations and the implications of these findings for tumorigenesis.
Involvement of Laccase2 in Cuticle Sclerotization of the Whitefly, Bemisia tabaci Middle East–Asia Minor 1
Authors: Yang Chun-Hong , Zhang Qi , Zhu Wan-Qing , Shi Yan , Cao He-He , Guo Lei , Chu Dong , Lu Zhaozhi , Liu Tong-Xian
Published: May 2022

Cuticle sclerotization is critical for insect survival. Laccase2 (Lac2) is a phenol oxidase that plays a key role in cuticle formation and pigmentation in a variety of insects. However, the function of Lac2 in whitefly, Bemisia tabaci, remains unclear. In this study, we identified a BtLac2 gene in B. tabaci MEAM1 and found that BtLac2 was expressed in all stages. It was highly expressed in the egg stage, followed by nymph and adult. Moreover, the expression of BtLac2 was higher in the cuticle than in other tissues. Knockdown of BtLac2 in nymphs produced thinner and fragile cuticles, which significantly increased the mortality rate, extended the development duration of nymphs, and decreased the emergence rate of adults. This result demonstrates that BtLac2 plays an important role in the cuticle hardening of B. tabaci and suggests a potential management strategy using RNAi to knock down BtLac2 expression.
Characteristics and Patient Reported Outcome Measures in Lipedema Patients—Establishing a Baseline for Treatment Evaluation in a High-Volume Center
Authors: Hamatschek Matthias , Knors Henning , Klietz Marie-Luise , Wiebringhaus Philipp , Aitzetmueller Matthias , Hirsch Tobias , Kueckelhaus Maximilian
Published: May 2022

Lipedema patients suffer not only from visual stigma but also reduction in their quality of life through pain and performance loss in daily life. In clinical practice, it is still difficult to reliably diagnose the disease. This study aims to provide further insights into the characteristics of lipedema patients of all stages and provide a baseline prior to surgery for a surgical treatment evaluation by means of patient-reported outcome measures. Methods: Patients completed a lipedema-specific questionnaire containing 50 items, the World Health Organization Quality of Life BREF (WHOQOL-BREF) and the Patient Health Questionnaire 9 (PHQ-9). The data were analyzed using SPSS statistics 27. Patients who had already received liposuction were excluded. Results: Five hundred and eleven patients were included, of whom 337 completed the PHQ9 and 333 completed the WHOQOL-BREF questionnaires. The general characteristics of lipedema patients, especially the daily symptoms, are described. Previous observations, such as the frequent occurrence of hypothyroidism and the low rate of type 2 diabetes, were confirmed. Over 49% suffer from severe impairments in their jobs, whereby the disease shows a familial accumulation. The results of the WHOQOL-BREF and the PHQ-9 suggest a high level of mental stress. Discussion: As surgical intervention in lipedema patients is gaining traction, its effects should be well-documented. Therefore, a comprehensive baseline needs to be established prior to surgical treatment. The psychological components are just as important as the inclusion of daily impairments.
Mobile Bearing versus Fixed Bearing for Unicompartmental Arthroplasty in Monocompartmental Osteoarthritis of the Knee: A Meta-Analysis
Authors: Migliorini Filippo , Maffulli Nicola , Cuozzo Francesco , Elsner Karen , Hildebrand Frank , Eschweiler Jörg , Driessen Arne
Published: May 2022

Introduction: Whether mobile-bearing (MB) unicompartmental knee arthroplasty (UKA) performs better than fixed-bearing (FB) implants in patients with monocompartmental osteoarthritis (OA) still remains unclear. Therefore, a meta-analysis comparing MB versus FB for UKA was conducted to investigate the possible advantages of MB versus FB in patient-reported outcome measures (PROMs), range of motion (ROM), and complications. We hypothesised that the MB design performs better than FB. Methods: This systematic review was conducted according to the 2020 PRISMA guidelines. In December 2021, PubMed, Web of Science, Google Scholar, and Embase were accessed, with no time constraints. All the clinical investigations comparing MB versus FB bearing for UKA were accessed. Only studies published in peer-reviewed journals were considered. Studies reporting data on revision settings were excluded, as were those combining unicompartmental and total knee arthroplasty. Results: Data from 25 studies (4696 patients) were collected; 58% (2724 of 4696 patients) were women. The mean length of follow-up was 45.8 ± 43.2. The mean age of the patients was 65.0 ± 5.6 years. No difference was found in range of motion (p = 0.05), Knee Scoring System (p = 0.9), function subscale (p = 0.2), and Oxford Knee Score (p = 0.4). No difference was found in the rate of revision (p = 0.2), aseptic loosening (p = 0.9), deep infections (p = 0.99), fractures (p = 0.6), and further extension of OA to the contralateral joint compartment (p = 0.2). Conclusion: The present meta-analysis failed to identify the possible superiority of the MB implants over the FB for UKA in patients with monocompartmental knee osteoarthritis. Long observational investigations are required to evaluate possible long-term complications and implant survivorship. These results should be interpreted within the limitations of the present study.
Current Trends in Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Peritoneal Disease from Appendiceal and Colorectal Malignancies
Authors: Harper Megan M. , Kim Joseph , Pandalai Prakash K.
Published: May 2022

Peritoneal carcinomatosis (PC) is a poor prognostic factor for all malignancies. This extent of metastatic disease progression remains difficult to treat with systemic therapies due to poor peritoneal vascularization resulting in limited drug delivery and penetration into tissues. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are surgical interventions that directly target peritoneal tumors and have improved outcomes for PC resulting from appendiceal and colorectal cancer (CRC). Despite these radical therapies, long-term survival remains infrequent, and recurrence is common. The reasons for these outcomes are multifactorial and signal the need for the continued development of novel therapeutics, techniques, and approaches to improve outcomes for these patients. Here, we review landmark historical studies that serve as the foundation for current recommendations, recent discoveries, clinical trials, active research, and areas of future interest in CRS/HIPEC to treat PC originating from appendiceal and colorectal malignancies.
Predictive Value of the Third Ventricle Width for Neurological Status in Multiple Sclerosis
Authors: Guenter Wojciech , Betscher Ewa , Bonek Robert
Published: May 2022

The third ventricle width (3VW) is an easily calculated measure of brain atrophy. The aim of this study was to evaluate the relation of 3VW to cognitive impairment with adjustment for demographic and clinical confounders, including depression, anxiety, and fatigue, as well as to disability in patients with multiple sclerosis (MS). Symbol Digit Modalities Test, California Verbal Learning Test, Brief Visuospatial Memory Test-Revised, Expanded Disability Status Scale (EDSS), Hospital Anxiety and Depression Scale, and Modified Fatigue Impact Scale (MFIS) were analysed in 93 patients with MS. Neuropsychological performance was compared to that of 150 healthy controls. Axial images from 3D FLAIR were used to measure 3VW. In total, 25% of MS patients were impaired in at least two neuropsychological tests. Cognitive impairment and EDSS were associated with 3VW. Age and 3VW were the strongest predictors of cognitive impairment. The multiple regression model including age, 3VW, education, EDSS, and MFIS explained 63% of the variance of neuropsychological tests results, whereas 3VW, age and duration of the disease were significant predictors of EDSS. This study confirms the predictive value of 3VW for neurological status of patients with MS, especially for cognitive impairment after adjustment for demographic and clinical confounders.
Intraocular Pressure Measurement in Childhood Glaucoma under Standardized General Anaesthesia: The Prospective EyeBIS Study
Authors: Strzalkowska Alicja , Pirlich Nina , Stingl Julia V. , Schuster Alexander K. , Rezapour Jasmin , Wagner Felix M. , Buse Justus , Hoffmann Esther M.
Published: May 2022

Objective: We aimed to compare intraocular pressure (IOP) measurements using iCare® PRO rebound tonometry (iCare) and Perkins applanation tonometry (Perkins) in childhood glaucoma subjects and healthy children and the influence of anaesthesia depth, age and corneal thickness. Material: Prospective clinical, case-control study of children who underwent an ophthalmologic examination under general anaesthesia according to our protocol. Children were 45.45 ± 29.76 months old (mean ± SD (standard deviation)). Of all children, 54.05% were female. IOP was taken three times (T1–T3), according to duration and the depth of anaesthesia. The order of measurement alternated, starting with iCare. Agreement between the device measurements was evaluated using Bland–Altman analysis. Results: 53 glaucoma subjects and 22 healthy controls. Glaucoma subjects: IOP measured with iCare was at T1: 27.2 (18.1–33.8), T2: 21.6 (14.8–30.6), T3: 20.4 mmHg (14.5–27.0) and Perkins 17.5 (12.0–23.0), 15.5 (10.5–20.5), 15.0 mmHg (10.5–21.0) (median ± IQR (interquartile range)). Healthy controls: IOP with iCare: T1: 13.3 (11.1–17.0), T2: 10.6 (8.1–12.4), T3: 9.6 mmHg (7.7–11.7) and Perkins 10.3 (8.0–12.0), 7.0 (5.5–10.5), 7.0 mmHg (5.5–8.5) (median ± IQR). The median IOP was statistically significantly higher with iCare than with Perkins (p < 0.001) in both groups. The mean difference (iCare and Perkins) was 6.0 ± 6.1 mmHg for T1–T3, 7.3 at T1, 6.0 at T2, 4.9 mmHg at T3. Conclusion: The IOP was the highest in glaucoma subjects and healthy children at T1 (under sedation), independently of the measurement method. iCare always leads to higher IOP compared to Perkins in glaucoma and healthy subjects, regardless of the duration of anesthesia.
Protozoan Intestinal Parasitic Infection in Patients with Hematological Malignancies
Authors: Łanocha Aleksandra , Łanocha-Arendarczyk Natalia , Wilczyńska Dominika , Zdziarska Barbara , Kosik-Bogacka Danuta
Published: May 2022

The aim of this study was to evaluate the frequency of gastrointestinal protozoan infection in patients with hematological malignancies (HMs) undergoing intensive hemato-oncological treatment and to determine the influence of certain biological factors on the incidence of intestinal parasite infection. Stool samples were collected from hematological malignancy patients (n = 50) hospitalized at the Department of Hematology and Transplantology of the Pomeranian Medical University in Szczecin. The control group consisted of 50 healthy participants. We used a direct smear examination and a commercial immunoenzymatic test. Intestinal protozoans were detected in 16% of patients with hematological malignancies and in 6% of individuals in the control group. In stool samples from patients with HM, cysts of Giardia intestinalis (2%), oocysts of Cryptosporidium spp. (10%), vacuolar forms of potentially pathogenic Blastocystis spp. (2%), and cysts of nonpathogenic Entamoeba coli (2%) were found. Cryptosporidium spp. and Giardia intestinalis coproantigens were detected in 5 (10%) and 1 (2%) patients with HM, respectively. In three participants from the control group, vacuolar forms of Blastocystis spp. were found. In the patients with HM, a significantly higher prevalence of intestinal parasite infection was found in individuals working in the garden without protective gloves and those in contact with animals. In patients with hematological malignancies, intestinal parasites should be excluded, even during intensive chemotherapy treatment.
Cyclic Metronomic Chemotherapy for Pediatric Tumors: Six Case Reports and a Review of the Literature
Authors: Carcamo Benjamin , Francia Giulio
Published: May 2022

We report a retrospective case series of six Hispanic children with tumors treated with metronomic chemotherapy. The six cases comprised one rhabdoid tumor of the kidney, one ependymoma, two medulloblastomas, one neuroblastoma, and a type II neurocytoma of the spine. Treatment included oral cyclophosphamide daily for 21 days alternating with oral etoposide daily for 21 days in a backbone of daily valproic acid and celecoxib. In one case, celecoxib was substituted with sulindac. Of the six patients, three showed complete responses, and all patients showed some response to metronomic therapy with only minor hematologic toxicity. One patient had hemorrhagic gastritis likely associated with NSAIDs while off prophylactic antacids. These data add to a growing body of evidence suggesting that continuous doses of valproic acid and celecoxib coupled with alternating metronomic chemotherapy of agents such as etoposide and cyclophosphamide can produce responses in pediatric tumors relapsing to conventional dose chemotherapy.
Epidemiology and Treatment of Distal Radius Fractures in Finland—A Nationwide Register Study
Authors: Raudasoja Leena , Aspinen Samuli , Vastamäki Heidi , Ryhänen Jorma , Hulkkonen Sina
Published: May 2022

A distal radius fracture (DRF) is one of the most common fractures in emergency units, the treatment of which requires considerable health care resources. We analyzed the incidence rate for DRFs and the incidence rate of operative treatment over a five-year period, 2015–2019, for the entire population of Finland and all ages. Data was obtained from the Finnish National Care Register for Health Care. The results were counted as cases per 100,000 person/years and standardized with the European Standard Population 2013. The mean annual incidence rate of DRF was 204.90 (203.21–206.59) in specialist care and 69.53 (68.55–70.52) in primary care. It peaked among the pediatric population and among elderly women, in whom it was more than four times as common compared to men of the same age. No increase in the incidence rate of DRFs was found. The mean incidence rate of operative treatment was 45.66 (45.66–45.66)/100,000 person/years, 2015–2019; women were more likely to undergo operative treatment. Altogether, 15–18% of DRFs were operated on over the study period. The annual incidence rate of operations seemed to plateau compared to earlier studies in Finland.
Metronomic Chemotherapy in Prostate Cancer
Authors: Wysocki Piotr J. , Lubas Maciej T. , Wysocka Malgorzata L.
Published: May 2022

Despite the significant expansion of the therapeutic armamentarium associated with the introduction of novel endocrine therapies, cytotoxic agents, radiopharmaceuticals, and PARP inhibitors, progression of metastatic castration-resistant prostate cancer (mCRPC) beyond treatment options remains the leading cause of death in advanced prostate cancer patients. Metronomic chemotherapy (MC) is an old concept of wise utilization of cytotoxic agents administered continuously and at low doses. The metronomic is unique due to its multidimensional mechanisms of action involving: (i) inhibition of cancer cell proliferation, (ii) inhibition of angiogenesis, (iii) mitigation of tumor-related immunosuppression, (iv) impairment of cancer stem cell functions, and (v) modulation of tumor and host microbiome. MC has been extensively studied in advanced prostate cancer before the advent of novel therapies, and its actual activity in contemporary, heavily pretreated mCRPC patients is unknown. We have conducted a prospective analysis of consecutive cases of mCRPC patients who failed all available standard therapies to find the optimal MC regimen for phase II studies. The metronomic combination of weekly paclitaxel 60 mg/m2 i.v. with capecitabine 1500 mg/d p.o. and cyclophosphamide 50 mg/d p.o. was selected as the preferred regimen for a planned phase II study in heavily pretreated mCRPC patients.
Multimodality Imaging in the Study of the Left Atrium
Authors: Moral Sergio , Abulí Marc , Vilardell Pau , Trucco Emilce , Ballesteros Esther , Brugada Ramon
Published: May 2022

The left atrium (LA) plays a vital role in maintaining normal cardiac function. Many cardiac diseases involve the functioning of the LA directly or indirectly. For this reason, the study of the LA has become a priority for today’s imaging techniques. Assessment of LA size, function and wall characteristics is routinely performed in cardiac imaging laboratories when a patient undergoes transthoracic echocardiography. However, in cases when the LA is the focus of disease management, such as in atrial fibrillation or left atrial appendage closure, the use of multimodality is critical. Knowledge of the usefulness of each cardiac imaging technique for the study of LA in these patients is crucial in order to choose the most appropriate treatment. While echocardiography is the most widely performed technique for its evaluation and the study of wall deformation analysis is increasingly becoming more reliable, multidetector computed tomography allows a detailed analysis of its anatomy to be carried out in 3D reconstructions that help in the approach to interventional treatments. In addition, the evaluation of the wall by cardiac magnetic resonance imaging or the generation of electroanatomical maps in the electrophysiology room have become essential tools in the treatment of multiple atrial pathologies. For this reason, the goal of this review article is to describe the basic anatomical and functional information of the LA as well as their study employing the main imaging techniques currently available, so that practitioners specializing in cardiac imaging techniques can use these tools in an accurate and clinically useful manner.
Sacral Dimple, Conjunctiva, and Nipple as Less Obvious Pemphigus Vulgaris Locations around Natural Body Orifices: A Report of Three Cases
Authors: Jałowska Magdalena , Gornowicz-Porowska Justyna , Bowszyc-Dmochowska Monika , Dmochowski Marian
Published: May 2022

In this paper, we present our own clinical-laboratory experience concerning three less obvious presentations of pemphigus vulgaris (PV) and discuss the pertinent literature. The involvement of the sacral dimple reported here for the first time, as well as the nipple and the eyes, could initially be misleading clinically. These less stereotypical localizations may occur due to the transition of different epithelia, each with varying levels of cadherin (desmoglein, desmocollin) and thus altered sensitivity to mechanical stress. The role of dermatologists who have experience in treating autoimmune blistering dermatoses is fundamental for identifying promptly the initial and exacerbating PV lesions in such unusual locations.
Evaluation of Scar Quality after Treatment of Superficial Burns with Dressilk® and Suprathel®—In an Intraindividual Clinical Setting
Authors: Schiefer Jennifer , Andreae Janine , Fuchs Paul , Lefering Rolf , Heidekrueger Paul , Schulz Alexandra , Bagheri Mahsa
Published: May 2022

Background: Various synthetic and biological wound dressings are available for the treatment of superficial burns, and standard care differs among hospitals. Nevertheless, the search for an ideal wound dressing offering a safe healing environment as well as optimal scar quality while being economically attractive is a continuing process. In recent years, Dressilk®, which consists of pure silk, has become the standard of care for the treatment of superficial burns in our hospital. However, no long-term scar-evaluation studies have been performed to compare Dressilk® with the often-used and more expensive Suprathel® in the treatment of superficial burns. Methods: Subjective and objective scar evaluations were performed three, six, and twelve months after treatment in patients who received simultaneous treatment of 20 superficial burn wounds with both Suprathel® and Dressilk®. The evaluations were performed using the Vancouver Scar Scale, the Cutometer®, Mexameter®, Tewameter®, and the O2C®. Results: Both dressings showed mostly equivalent results in subjective scar evaluations. In the objective scar evaluations, the wounds treated with Dressilk® showed a faster return to the qualities of non-injured skin. Wound areas treated with the two dressings showed no significant differences in elasticity and transepidermal water loss after 12 months. Only oxygen saturation was significantly lower in wound areas treated with Suprathel® (p = 0.008). Subjectively, wound areas treated with Dressilk® showed significantly higher pigmentation after six months, which was not apparent after 12 months. Conclusion: Both wound dressings led to esthetically satisfying scar recovery without significant differences from normal uninjured skin after 12 months. Therefore, Dressilk® remains an economically and clinically interesting alternative to Suprathel® for the treatment of superficial burns.
From Animal to Human: (Re)using Acellular Extracellular Matrices for Temporomandibular Disc Substitution
Authors: Trindade Daniela , Alves Nuno , Moura Carla
Published: May 2022

Current treatments for temporomandibular joint (TMJ) disc dysfunctions are not fully effective and lack regenerative capacity. Therefore, the search for tissue-engineered materials for TMJ disc substitution is critical to fill this gap. Decellularization presents tremendous potential, as it is possible to obtain an extracellular matrix with an adequate biomechanical structure and biochemical components. However, its application to the TMJ disc is still in progress, since there are few studies in the literature, and those that exist have many gaps in terms of characterisation, which is decisive to ensure its success. Ultimately, we intend to emphasize the importance of the decellularization technique for the development of an engineered TMJ disc.
Big–Little Adaptive Neural Networks on Low-Power Near-Subthreshold Processors
Authors: Shen Zichao , Howard Neil , Nunez-Yanez Jose
Published: May 2022

This paper investigates the energy savings that near-subthreshold processors can obtain in edge AI applications and proposes strategies to improve them while maintaining the accuracy of the application. The selected processors deploy adaptive voltage scaling techniques in which the frequency and voltage levels of the processor core are determined at the run-time. In these systems, embedded RAM and flash memory size is typically limited to less than 1 megabyte to save power. This limited memory imposes restrictions on the complexity of the neural networks model that can be mapped to these devices and the required trade-offs between accuracy and battery life. To address these issues, we propose and evaluate alternative ‘big–little’ neural network strategies to improve battery life while maintaining prediction accuracy. The strategies are applied to a human activity recognition application selected as a demonstrator that shows that compared to the original network, the best configurations obtain an energy reduction measured at 80% while maintaining the original level of inference accuracy.
Research on COD Soft Measurement Technology Based on Multi-Parameter Coupling Analysis Method
Authors: Zhang Yurui , Duan Zhiyong , Yi Anzhe , Hu Jiaqi , Chen Yanhu
Published: May 2022

This paper presents a soft measurement technique for COD (Chemical Oxygen Demand) based on the multiparameter coupling analysis method. First, through mechanism analysis and correlation analysis of historical data during the measurement process, water quality parameters, such as hydrogen potential (PH), dissolved oxygen (DO), turbidity (TU), and electrical conductivity (EC), can be used to estimate COD values. To further improve the estimation accuracy of the water quality parameter model, we adopted a modeling method combining a BP neural network and support vector machine, which showed an average relative error of 6.13% and an absolute coefficient of up to 0.9605. Finally, experiments in a lake environment demonstrate that this method shows excellent performance, with highly reliable and accurate prediction results.
Stemphylium lycopersici Nep1-like Protein (NLP) Is a Key Virulence Factor in Tomato Gray Leaf Spot Disease
Authors: Lian Jiajie , Han Hongyu , Chen Xizhan , Chen Qian , Zhao Jiuhai , Li Chuanyou
Published: May 2022

The fungus Stemphylium lycopersici (S. lycopersici) is an economically important plant pathogen that causes grey leaf spot disease in tomato. However, functional genomic studies in S. lycopersici are lacking, and the factors influencing its pathogenicity remain largely unknown. Here, we present the first example of genetic transformation and targeted gene replacement in S. lycopersici. We functionally analyzed the NLP gene, which encodes a necrosis- and ethylene-inducing peptide 1 (Nep1)-like protein (NLP). We found that targeted disruption of the NLP gene in S. lycopersici significantly compromised its virulence on tomato. Moreover, our data suggest that NLP affects S. lycopersici conidiospore production and weakly affects its adaptation to osmotic and oxidative stress. Interestingly, we found that NLP suppressed the production of reactive oxygen species (ROS) in tomato leaves during S. lycopersici infection. Further, expressing the fungal NLP in tomato resulted in constitutive transcription of immune-responsive genes and inhibited plant growth. Through gene manipulation, we demonstrated the function of NLP in S. lycopersici virulence and development. Our work provides a paradigm for functional genomics studies in a non-model fungal pathogen system.
Elevated Ozone Concentration and Nitrogen Addition Increase Poplar Rust Severity by Shifting the Phyllosphere Microbial Community
Authors: Tao Siqi , Zhang Yunxia , Tian Chengming , Duplessis Sébastien , Zhang Naili
Published: May 2022

Tropospheric ozone and nitrogen deposition are two major environmental pollutants. A great deal of research has focused on the negative impacts of elevated O3 and the complementary effect of soil N addition on the physiological properties of trees. However, it has been overlooked how elevated O3 and N addition affect tree immunity in face of pathogen infection, as well as of the important roles of phyllosphere microbiome community in host–pathogen–environment interplay. Here, we examined the effects of elevated O3 and soil N addition on poplar leaf rust [Melampsora larici-populina] severity of two susceptible hybrid poplars [clone ‘107’: Populus euramericana cv. ‘74/76’; clone ‘546’: P. deltoides Í P. cathayana] in Free-Air-Controlled-Environment plots, in addition, the link between Mlp-susceptibility and changes in microbial community was determined using Miseq amplicon sequencing. Rust severity of clone ‘107’ significantly increased under elevated O3 or N addition only; however, the negative impact of elevated O3 could be significantly mitigated when accompanied by N addition, likewise, this trade-off was reflected in its phyllosphere microbial α-diversity responding to elevated O3 and N addition. However, rust severity of clone ‘546’ did not differ significantly in the cases of elevated O3 and N addition. Mlp infection altered microbial community composition and increased its sensitivity to elevated O3, as determined by the markedly different abundance of taxa. Elevated O3 and N addition reduced the complexity of microbial community, which may explain the increased severity of poplar rust. These findings suggest that poplars require a changing phyllosphere microbial associations to optimize plant immunity in response to environmental changes.
Effect of Tumor Targeted-Anthracycline Nanomedicine, HPMA Copolymer-Conjugated Pirarubicin (P-THP) against Gynecological Malignancies
Authors: Yanazume Shintaro , Fang Jun , Islam Rayhanul , Gao Shanghui , Kobayashi Hiroaki
Published: May 2022

Anthracyclines are important for the treatment of gynecological malignancies, but their effects are modest, and one of the major reasons is the lack of a tumor-targeting property. To overcome this drawback, a poly (hydroxypropyl meta-acrylamide) conjugated with tetrahydropyraryl doxorubicin (P-THP) has been developed, which exhibits a highly tumor-specific accumulation owing to the enhanced permeability and retention effect. The effect of P-THP has been confirmed by using various cell lines and solid tumor models, while its effect on gynecological malignancies have not been investigated. In this regard, human uterine sarcoma cell line with metastatic potential MEA-SA C9 high, epithelial ovarian cancer cell line A2780 and its cisplatin-resistant line A2780cis, and DOX-resistant line A2780ADR were used in this study, and the therapeutic effect as well as the safety profiles of P-THP were investigated compared to native THP, cisplatin, and paclitaxel, which are commonly used for gynecological malignancies, both in vitro and in vivo. Similar to native THP, a dose-dependent toxicity of P-THP was identified in all cell lines. Moreover, the IC50 values in the 3 h following P-THP were 1.5–10 times higher than those at 72 h, though the intracellular uptake of P-THP in all cells were 2–10-fold less than THP. In vivo studies using xenograft tumor models revealed that P-THP significantly suppressed the MES-SA C9 high, A2780, and A2780cis tumor growth at the dose of 15 mg/kg (THP equivalent), which is three times above the maximal tolerance dose of native THP, while no body weight loss or acute death occurred. However, in A2780ADR cells and the xenograft model, no significant difference in the therapeutic effect was observed between THP and P-THP, suggesting that P-THP exhibits its effect depending on the release of the active free THP in tumor tissues, and thus the internalization into tumor cells. These findings indicates that P-THP has the potential as a therapeutic for gynecological malignancies to improve the therapeutic outcomes and survival rates of patients, even in refractory patients.
The Impact of Human Activities on Net Primary Productivity in a Grassland Open-Pit Mine: The Case Study of the Shengli Mining Area in Inner Mongolia, China
Authors: Yang Fei , Wang Jinyang , Zhang Chengye , Li Jun , Xie Huizhen , Zhuoge Zeren
Published: May 2022

In grassland open-pit mining areas, net primary productivity (NPP) is mainly affected by climate conditions and human activities. The identification and assessment of the influence of human activities on NPP is important for mining production and the implementation of ecological restoration. In this study, we explored the influence of human activities on the NPP in the Shengli mining area in Inner Mongolia, China by using the Carnegie–Ames–Stanford Approach (CASA) model and the Chikugo model, in which a calibration method was applied. An analysis of four representative years showed that the proportion of NPP induced by human activities reached 56.2%, that the percentage of pixels with an inhibitory effect on NPP was 99% in 2011 with the highest intensity of mining activity, and that these two values decreased to 11.9% and 69% in 2020, respectively, with the steady implementation of ecological restoration. Moreover, from the analysis of global and local spatial correlation, mining activities and ecological restoration aggravated and weakened the aggregation of NPP induced by human activities, respectively.
Island Extractions in the Wild: A Corpus Study of Adjunct and Relative Clause Islands in Danish and English
Authors: Müller Christiane , Eggers Clara Ulrich
Published: May 2022

Adjuncts and relative clauses are traditionally classified as strong islands for extraction across languages. However, the Mainland Scandinavian (MSc.) languages have been reported to differ from e.g., English in allowing extraction from adjunct and relative clauses. In order to investigate the distribution of possible island extractions in these languages based on naturally produced material, we conducted two exploratory corpus studies on adjunct and relative clause extraction in Danish and in English. Results suggest that both extraction from finite adjuncts and from relative clauses appears at a non-trivial rate in naturally produced Danish, which supports the claim that these structures are not strong islands in Danish. In English, we also found a non-trivial amount of examples displaying extraction from finite adjuncts, as well as a small number of cases of relative clause extraction. This finding presents a potential challenge to the claim that English differs from MSc. in never allowing extraction from strong islands. Furthermore, our results show that both languages appear to share certain trends that can be observed in the extraction examples regarding the type of extraction dependency, the type of adjunct clause featured in adjunct clause extraction, and the type of matrix predicate featured in relative clause extraction.
Consensus Enolase of Trypanosoma Cruzi: Evaluation of Their Immunogenic Properties Using a Bioinformatics Approach
Authors: Diaz-Hernandez Alejandro , Gonzalez-Vazquez Maria Cristina , Arce-Fonseca Minerva , Rodríguez-Morales Olivia , Cedillo-Ramirez Maria Lilia , Carabarin-Lima Alejandro
Published: May 2022

There is currently no vaccine against American trypanosomiasis, caused by the parasite Trypanosoma cruzi. This is due to the genomic variation observed in the six DTUs of T. cruzi. This work aims to propose a consensus sequence of the enolase protein from different strains of T. cruzi and mainly evaluate its immunogenic properties at the bioinformatic level. From specialized databases, 15 sequences of the enolase gene were aligned to obtain a consensus sequence, where this sequence was modeled and then evaluated and validated through different bioinformatic programs to learn their immunogenic potential. Finally, chimeric peptides were designed with the most representative epitopes. The results showed high immunogenic potential with six epitopes for MHC-I, and seven epitopes for MHC-II, all of which were highly representative of the enolase present in strains from the American continent as well as five epitopes for B cells. Regarding the computational modeling, molecular docking with Toll-like receptors showed a high affinity and low constant of dissociation, which could lead to an innate-type immune response that helps to eliminate the parasite. In conclusion, the consensus sequence proposed for enolase is capable of providing an ideal immune response; however, the experimental evaluation of this enolase consensus and their chimeric peptides should be a high priority to develop a vaccine against Chagas disease.
Chromatographic Fractionation of Penicillium polonicum Fermentation Metabolites in Search of the Nephrotoxin(s) for Rats
Authors: Miljkovic Ana , Mantle Peter
Published: May 2022

Complex renal histopathological changes in rats, in silent response to dietary contamination with wheat moulded by a common Penicillium from the Balkans, have long eluded attribution of a causal toxin. So far, water-soluble amphoteric glyco-peptides seem responsible, at least for the nuclear pyknoses in nephron epithelia after several days of dietary exposure. Recently, refined histology analysis has diagnosed pyknosis as apoptosis, and followed the finding through application of medium-pressure liquid chromatography, anion exchange and silica layer chromatography to fractionate a water/alcohol-soluble extract of a fungal fermentation on wheat. Proline was revealed, with other amino acids, in acid hydrolysate of the fermentation extract. Application of mass spectrometry has recognized prominent ions (m/z 550 and 564) correlated with fragmentations consistent with a terminal proline moiety for the putative toxins, coupled with other structural fragments and correlated with apoptosis. Use of 14C-proline in probing Penicillium polonicum fermentation to aid isolation of the new potential toxins, along with application of gel electrophoresis, may further aid characterization of the apoptosis toxin(s). The present focus on proline peptides in mycotoxicosis fits easily with their increasingly recognised pharmacological activity associated with proline’s rigid secondary amine structure, which causes conformational contortion in peptides. Nevertheless, there remains the striking rat renal karyocytomegaly by P. polonicum, for which there is yet no causative mycotoxin.
Enhanced Cellular Materials through Multiscale, Variable-Section Inner Designs: Mechanical Attributes and Neural Network Modeling
Authors: Karathanasopoulos Nikolaos , Rodopoulos Dimitrios C.
Published: May 2022

In the current work, the mechanical response of multiscale cellular materials with hollow variable-section inner elements is analyzed, combining experimental, numerical and machine learning techniques. At first, the effect of multiscale designs on the macroscale material attributes is quantified as a function of their inner structure. To that scope, analytical, closed-form expressions for the axial and bending inner element-scale stiffness are elaborated. The multiscale metamaterial performance is numerically probed for variable-section, multiscale honeycomb, square and re-entrant star-shaped lattice architectures. It is observed that a substantial normal, bulk and shear specific stiffness increase can be achieved, which differs depending on the upper-scale lattice pattern. Subsequently, extended mechanical datasets are created for the training of machine learning models of the metamaterial performance. Thereupon, neural network (NN) architectures and modeling parameters that can robustly capture the multiscale material response are identified. It is demonstrated that rather low-numerical-cost NN models can assess the complete set of elastic properties with substantial accuracy, providing a direct link between the underlying design parameters and the macroscale metamaterial performance. Moreover, inverse, multi-objective engineering tasks become feasible. It is shown that unified machine-learning-based representation allows for the inverse identification of the inner multiscale structural topology and base material parameters that optimally meet multiple macroscale performance objectives, coupling the NN metamaterial models with genetic algorithm-based optimization schemes.
Duo Emission of CVD Nanodiamonds Doped by SiV and GeV Color Centers: Effects of Growth Conditions
Authors: Bogdanov Kirill V. , Baranov Mikhail A. , Feoktistov Nikolay A. , Kaliya Ilya E. , Golubev Valery G. , Grudinkin Sergey A. , Baranov Alexander V.
Published: May 2022

The investigation of the hot filament chemical vapor deposition nanodiamonds with simultaneously embedded luminescent GeV− and SiV− color centers from solid sources showed that both the absolute and relative intensities of their zero-phonon lines (at 602 and 738 nm) depend on nanodiamond growth conditions (a methane concentration in the CH4/H2 gas mixture, growth temperature, and time). It is shown that a controlled choice of parameters of hot filament chemical vapor deposition synthesis makes it possible to select the optimal synthesis conditions for tailoring bicolor fluorescence nanodiamond labels for imaging biological systems.
Development and Characterizations of Pullulan and Maltodextrin-Based Oral Fast-Dissolving Films Employing a Box–Behnken Experimental Design
Authors: Shah Kiramat Ali , Gao Binbin , Kamal Robia , Razzaq Anam , Qi Sun , Zhu Qiu-Ning , Lina Song , Huang Linyu , Cremin Grainne , Iqbal Haroon , Menaa Farid , Cui Jing-Hao
Published: May 2022

Migraine is a neurological disorder characterized by severe headaches, visual aversions, auditory, and olfactory disorders, accompanied by nausea and vomiting. Zolmitriptan (ZMT®) is a potent 5HT1B/1D serotonin receptor agonist frequently used for the treatment of migraine. It has erratic absorption from the gastrointestinal tract (GIT), but its oral bioavailability is low (40–45%) due to the hepatic metabolism. This makes it an ideal candidate for oral fast dissolving formulations. Hence, the current study was undertaken to design and develop oral fast-dissolving films (OFDFs) containing ZMT for migraine treatment. The OFDFs were formulated by the solvent casting method (SCM) using Pullulan (PU) and maltodextrin (MDX) as film-forming agents and propylene glycol (PG) as a plasticizer. The strategy was designed using Box–Behnken experimental design considering the proportion of PU:MDX and percentage of PG as independent variables. The effectiveness of the OFDF’s was measured based on the following responses: drug release at five min, disintegration time (D-time), and tensile strength (TS). The influence of formulation factors, including percent elongation (%E), thickness, water content, moisture absorption, and folding endurance on ZMT-OFDFs, were also studied. The results showed a successful fabrication of stable ZMT-OFDFs, with surface uniformity and amorphous shape of ZMT in fabricated films. The optimized formulation showed a remarkable rapid dissolution, over 90% within the first 5 min, a fast D-time of 18 s, and excellent mechanical characteristics. Improved maximum plasma concentration (C max) and area under the curve (AUC 0–t) in animals (rats) treated with ZMT-OFDFs compared to those treated with an intra-gastric (i-g) suspension of ZMT were also observed. Copolymer OFDFs with ZMT is an exciting proposition with great potential for the treatment of migraine headache. This study offers a promising strategy for developing ZMT-OFDFs using SCM. ZMT-OFDFs showed remarkable rapid dissolution and fast D-time, which might endeavor ZMT-OFDFs as an auspicious alternative approach to improve patient compliance and shorten the onset time of ZMT in migraine treatment.
Hydrophilic CO-Releasing Material of PEGlyated Ruthenium Carbonyl Complex
Authors: Zhang Xiao , Guo Nan , Yang Shuhong , Khan Huma , Zhang Weiqiang
Published: May 2022

The poor water-solubility and instability of Ru(II) carbonyl complex hamper the therapeutic application as CO releasing materials (CO-RMs). To enhance the hydrophilicity and bio-utility of CO, a robust Ru(I) carbonyl sawhorse skeleton was grafted with water-soluble PEGylated sidearm. In this case, 12 PEGylated sawhorse Ru2(CO)4 complexes were prepared with satisfactory yields and characterized by IR and 1H- and 13C- NMR. X-ray diffraction analysis of CO-RM 8, 13 and 14 revealed the featured diruthenium sawhorse skeleton and PEGylated axial ligands. The flask-shaking method measures the water-solubility of CO-RMs, indicating that both bridging carboxylate ligands and PEGlyated axial ligands regulate the hydrophilicity of these CO-RMs. Under photolysis conditions, CO-RM 4–13 sustainable released therapeutic amounts of CO in the myoglobin assay. The correlation of the CO release kinetics and hydrophilicity of CO-RMs demonstrated that the more hydrophilic CO-RM released CO faster. The biological test found that the low cytotoxic CO-RM 4 showed a specific anticancer activity toward HT-29 tumour cells.
Ultrasonic Bending Vibration-Assisted Purification Experimental Study of 7085 Aluminum Alloy Melt
Authors: Shi Chen , He Jiangnan , Liao Hua , Mao Daheng
Published: May 2022

Aiming at the problem that melt inclusions in the casting process of 7085 aluminum alloy seriously affect the ingot quality, this study introduces ultrasonic bending vibration into the melt of the launder in the semi-continuous casting process of 7085 aluminum alloy and investigates the online purification effect of ultrasonic bending vibration on the melt of 7085 aluminum alloy through a metallographic analysis, SEM analysis, and EDS energy spectrum analysis. The results show that, under the action of the ultrasonic, the inclusions in the aluminum melt are transformed from a large number of elongated large inclusions with a size of more than 50 μm, and granular inclusions with a size of about 5–15 μm, into a small amount of smaller than 30 μm point-like small inclusions. In addition, the average area ratio of inclusions in the melted sample was reduced from 3.835 (±0.05)% to 0.458 (±0.05)%, and the residual refining agent in the aluminum melt was effectively removed. It was also found that under the action of ultrasonic bending vibration, the tiny inclusions in the melt aggregate with each other, and interact with the residual refining agent in the melt to further grow, and are attached to the inner surface of the ceramic cavity channel to be removed.
Surface Topographic Features after Milling of Additively Manufactured AlSi10Mg Aluminum Alloy
Authors: Struzikiewicz Grzegorz , Sioma Andrzej
Published: May 2022

The article presents selected issues related to material quality manufactured by selective laser sintering of AlSi10Mg alloy powder after milling. The workpiece was prepared and machined by down-milling and up-milling with tools made of high-speed steel. Breaches, pores and failure-like cracks on the machined surface were found, which negatively influenced the values of 3D surface roughness parameters. The occurring phenomena were analyzed and proposals for their explanation were made. The results of this research describe the effect of cutting parameters (the feed rate of f = 0.013–0.05 mm/tooth) on the values of parameters describing the surface quality and benchmarks. Topography measurements and 3D surface roughness parameters are presented, as well as the results of microscopic surface analysis. It was found that for aluminum alloy produced by the direct metal laser sintering (DMLS) method, the recommended machining method is down-milling.