bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational Tumor Infiltration Phenotypes Enable the Spatial and Genomic Analysis of Immune Infiltration in Colorectal Cancer
Authors: Failmezger Henrik , Zwing Natalie , Tresch Achim , Korski Konstanty , Schmich Fabian
Published: March 2021

Cancer immunotherapy has led to significant therapeutic progress in the treatment of metastatic and formerly untreatable tumors. However, drug response rates are variable and often only a subgroup of patients will show durable response to a treatment. Biomarkers that help to select those patients that will benefit the most from immunotherapy are thus of crucial importance. Here, we aim to identify such biomarkers by investigating the tumor microenvironment, i.e., the interplay between different cell types like immune cells, stromal cells and malignant cells within the tumor and developed a computational method that determines spatial tumor infiltration phenotypes. Our method is based on spatial point pattern analysis of immunohistochemically stained colorectal cancer tumor tissue and accounts for the intra-tumor heterogeneity of immune infiltration. We show that, compared to base-line models, tumor infiltration phenotypes provide significant additional support for the prediction of established biomarkers in a colorectal cancer patient cohort (n = 80). Integration of tumor infiltration phenotypes with genetic and genomic data from the same patients furthermore revealed significant associations between spatial infiltration patterns and common mutations in colorectal cancer and gene expression signatures. Based on these associations, we computed novel gene signatures that allow one to predict spatial tumor infiltration patterns from gene expression data only and validated this approach in a separate dataset from the Cancer Genome Atlas.
Efficacy and Feasibility of Programmed Death-1/Programmed Death Ligand-1 Blockade Therapy in Non-Small Cell Lung Cancer Patients With High Antinuclear Antibody Titers
Authors: Mouri Atsuto , Kaira Kyoichi , Yamaguchi Ou , Hashimoto Kosuke , Miura Yu , Shiono Ayako , Shinomiya Shun , Akagami Tomoe , Imai Hisao , Kobayashi Kunihiko , Kagamu Hiroshi
Published: March 2021

Background

Immune checkpoint inhibitor (ICI) therapy has been described to markedly improve patient survival. However, reports describing the antitumor therapeutic efficacy and safety of ICIs in patients with autoantibodies are scarce.

Methods

This study examined the efficacy and feasibility of ICIs in antinuclear antibody (ANA)-positive patients with non-small cell lung cancer (NSCLC). An ANA titer greater than 1:40 and 1:80 was defined as positive and high, respectively. Patients who were treated with ICIs at Saitama Medical University, International Medical Center between January 2016 and December 2018 were retrospectively reviewed.

Results

One hundred and nineteen of the 266 patients (44.7%) who received nivolumab, pembrolizumab, and atezolizumab had positive ANA titers. Their median age was 69 (range, 39–84) years. The overall response rate of the ANA-positive patients was 35.9% (37/103), which was not less than that of the ANA-negative group. The median progression-free survival in the ANA-positive group was 6.3 months versus 4.3 months in the ANA-negative group (p = 0.08). Twenty-seven ANA-positive patients (10.2%) had high ANA titers. However, ICI efficacy was not decreased in these patients. Regardless of the cutoff of ANA titers (1:40 or 1:80), the rate of patients who experienced adverse events were not significantly different between the two groups.

Conclusion

The administration of ICIs to ANA-positive patients has clinical benefits. The prevalence of adverse events in the ANA-positive group was not higher than that in the ANA-negative group.
RETRACTED: MiR-365a-3p-Mediated Regulation of HELLS/GLUT1 Axis Suppresses Aerobic Glycolysis and Gastric Cancer Growth
Authors: Yang Rui , Liu Gen , Han Limin , Qiu Yuheng , Wang Lulin , Wang Mei
Published: March 2021

Gastric cancer (GC) is a common and invasive malignancy, which lacks effective treatment and is the third main reason of cancer death. Metabolic reprogramming is one of the main reasons that GC is difficult to treat in various environments. Particularly, abnormal glycolytic activity is the most common way of metabolism reprogramming in cancer cells. Numerous studies have shown that microRNAs play important roles in reprogramming glucose metabolism. Here, we found a microRNA-miR-365a-3p, was significantly downregulated in GC according to bioinformatics analysis. Low expression of miR-365a-3p correlated with poor prognosis of GC patients. Overexpression of miR-365a-3p in GC cells significantly inhibited cell proliferation by inducing cell cycle arrest at G1 phase. Notably, miR-365a-3p induced downregulation of HELLS through binding to its 3′ untranslated region (UTR). Additionally, we found that miR-365a-3p suppressed aerobic glycolysis by inhibiting HELLS/GLUT1 axis. Lastly, we shown that overexpression of miR-365a-3p significantly inhibited tumor growth in nude mice. Conversely, Reconstituted the expression of HELLS rescued the suppressive effects of miR-365a-3p. Our data collectively indicated that miR-365a-3p functioned as a tumor suppressor in GC through downregulating HELLS. Therefore, targeting of the novel miR-365a-3p/HELLS axis could be a potentially effective therapeutic approach for GC.
More Favorable Short and Long-Term Outcomes for Screen-Detected Colorectal Cancer Patients
Authors: Spolverato Gaya , Capelli Giulia , Battagello Jessica , Barina Andrea , Nordio Susi , Finotti Elena , Mondi Isabella , Da Lio Corrado , Morpurgo Emilio , Navarro Josè Adolfo , Ceccato Fabio , Perin Alessandro , Pedrazzani Corrado , Turri Giulia , Zanus Giacomo , Campi Michela , Massani Marco , Di Giacomo Adriana , Prando Daniela , Agresta Ferdinando , Pucciarelli Salvatore , Zorzi Manuel , Rugge Massimo
Published: March 2021

Background

Screening significantly reduces mortality from colorectal cancer (CRC). Screen detected (SD) tumors associate with better prognosis, even at later stage, compared to non-screen detected (NSD) tumors. We aimed to evaluate the association between diagnostic modality (SD vs. NSD) and short- and long-term outcomes of patients undergoing surgery for CRC.

Materials and Methods

This retrospective cohort study involved patients aged 50–69 years, residing in Veneto, Italy, who underwent curative-intent surgery for CRC between 2006 and 2018. The clinical multi-institutional dataset was linked with the screening dataset in order to define diagnostic modality (SD vs. NSD). Short- and long-term outcomes were compared between the two groups.

Results

Of 1,360 patients included, 464 were SD (34.1%) and 896 NSD (65.9%). Patients with a SD CRC were more likely to have less comorbidities (p = 0.013), lower ASA score (p = 0.001), tumors located in the proximal colon (p = 0.0018) and earlier stage at diagnosis (p < 0.0001). NSD patients were found to have more aggressive disease at diagnosis, higher complication rate and higher readmission rate due to surgical complications (all p < 0.05). NSD patients had a significantly lower Disease Free Survival and Overall Survival (all p < 0.0001), even after adjusting by demographic, clinic-pathological, tumor, and treatment characteristics.

Conclusions

SD tumors were associated with better long-term outcomes, even after multiple adjustments. Our results confirm the advantages for the target population to participate in the screening programs and comply with their therapeutic pathways.
In Vivo 3-D Dose Verification Using PET/CT Images After Carbon-Ion Radiation Therapy
Authors: Sun Lining , Hu Weigang , Lai Songtao , Shi Leijun , Chen Junchao
Published: March 2021

Objective

To investigate the usefulness of positron emission tomography (PET) images obtained after carbon-ion irradiation for dose verification in carbon-ion radiotherapy.

Methods and Materials

An anthropomorphic head phantom was used in this study. Three cubes with volumes of 1, 4, and 10 ml were contoured as targets in the phantom CT through a treatment planning system. Treatment plans with six prescriptions from 2.5 to 10 Gy (2.5, 3, 5, 6, 8, and 10 Gy effective dose) were designed and delivered by 90° fixed carbon-ion beams, respectively. After irradiation of the phantom, a PET/CT scan was performed to fuse the treatment-planning CT image with the PET/CT image. The relationship between target volume and the standard uptake value (SUV) in PET/CT was evaluated for corresponding plan prescription. The MIM Maestro software was used for the image fusion and data analysis.

Results

SUV in the target had an approximate linear relationship with the effective dose. The same effective dose could generate a roughly equal SUV for different target volumes (p < 0.05).

Conclusions

It is feasible to verify the actual 3-D dose distribution of carbon-ion radiotherapy by the approach in this study.
Study of Combinatorial Drug Synergy of Novel Acridone Derivatives With Temozolomide Using in-silico and in-vitro Methods in the Treatment of Drug-Resistant Glioma
Authors: Chakravarty Malobika , Ganguli Piyali , Murahari Manikanta , Sarkar Ram Rup , Peters Godefridus Johannes , Mayur Y. C.
Published: March 2021

Drug resistance is one of the critical challenges faced in the treatment of Glioma. There are only limited drugs available in the treatment of Glioma and among them Temozolomide (TMZ) has shown some effectiveness in treating Glioma patients, however, the rate of recovery remains poor due to the inability of this drug to act on the drug resistant tumor sub-populations. Hence, in this study three novel Acridone derivative drugs AC2, AC7, and AC26 have been proposed. These molecules when combined with TMZ show major tumor cytotoxicity that is effective in suppressing growth of cancer cells in both drug sensitive and resistant sub-populations of a tumor. In this study a novel mathematical model has been developed to explore the various drug combinations that may be useful for the treatment of resistant Glioma and show that the combinations of TMZ and Acridone derivatives have a synergistic effect. Also, acute toxicity studies of all three acridone derivatives were carried out for 14 days and were found safe for oral administration of 400 mg/kg body weight on albino Wistar rats. Molecular Docking studies of acridone derivatives with P-glycoprotein (P-gp), multiple resistant protein (MRP), and O6-methylguanine-DNA methyltransferase (MGMT) revealed different binding affinities to the transporters contributing to drug resistance. It is observed that while the Acridone derivatives bind with these drug resistance causing proteins, the TMZ can produce its cytotoxicity at a much lower concentration leading to the synergistic effect. The in silico analysis corroborate well with our experimental findings using TMZ resistant (T-98) and drug sensitive (U-87) Glioma cell lines and we propose three novel drug combinations (TMZ with AC2, AC7, and AC26) and dosages that show high synergy, high selectivity and low collateral toxicity for the use in the treatment of drug resistant Glioma, which could be future drugs in the treatment of Glioblastoma.
The Protozoan Inhibitor Atovaquone Affects Mitochondrial Respiration and Shows In Vitro Efficacy Against Glucocorticoid-Resistant Cells in Childhood B-Cell Acute Lymphoblastic Leukaemia
Authors: Sbirkov Yordan , Ivanova Tsvetomira , Burnusuzov Hasan , Gercheva Kalina , Petrie Kevin , Schenk Tino , Sarafian Victoria
Published: March 2021

Childhood acute lymphoblastic leukaemia (cALL) accounts for about one third of all paediatric malignancies making it the most common cancer in children. Alterations in tumour cell metabolism were first described nearly a century ago and have been acknowledged as one of the key characteristics of cancers including cALL. Two of the backbone chemotherapeutic agents in the treatment of this disease, Glucocorticoids and L-asparaginase, are exerting their anti-leukaemic effects through targeting cell metabolism. Even though risk stratification and treatment regimens have improved cure rates to nearly 90%, prognosis for relapsed children remains poor. Therefore, new therapeutic approaches are urgently required. Atovaquone is a well-tolerated drug used in the clinic mainly against malaria. Being a ubiquinone analogue, this drug inhibits co-enzyme Q10 of the electron transport chain (ETC) affecting oxidative phosphorylation and cell metabolism. In this study we tested the effect of Atovaquone on cALL cells in vitro. Pharmacologically relevant concentrations of the inhibitor could effectively target mitochondrial respiration in both cALL cell lines (REH and Sup-B15) and primary patient samples. We found that Atovaquone leads to a marked decrease in basal respiration and ATP levels, as well as reduced proliferation, cell cycle arrest, and induction of apoptosis. Importantly, we observed an enhanced anti-leukaemic effect when Atovaquone was combined with the standard chemotherapeutic Idarubicin, or with Prednisolone in an in vitro model of Glucocorticoid resistance. Repurposing of this clinically approved inhibitor renders further investigations, but also presents opportunities for fast-track trials as a single agent or in combination with standard chemotherapeutics.
Survival-Weighted Health Profiles in Nasopharyngeal Cancer Patients
Authors: Lai Chia-Hsuan , Chen Wen-Cheng , Fang Chiung-Cheng , Chen Miao-Fen
Published: March 2021

Introduction

In treating nasopharyngeal cancer (NPC) patients, excellent tumor control and patient survival rates can be achieved in the era of intensity-modulated radiotherapy (IMRT). However, treatment-related toxicities affect the quality of life (QoL) of NPC survivors. This study was devised to estimate the life expectancy (LE), quality-adjusted life expectancy (QALE) and survival-weighted psychometric scores (SWPS) in NPC patients.

Methods

A sample of 875 non-metastatic NPC patients diagnosed between January 1, 2009 and June 30, 2013 was collected for estimation of lifetime survival function. All patients were followed up until death or censored on December 31, 2015. To obtain the utility and psychometric score for estimation of LE, QALE, and SWPS, 99 patients were measured with the Taiwanese version of the EuroQol instrument (EQ-5D) and the Taiwan Chinese versions of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 and QLQ-H&N35 between October 1, 2013 and December 31, 2017. By utilizing linear extrapolation of a logit-transformed curve, the LE of NPC patients can be estimated. The QALE and SWPS can be obtained by combining the LE and the corresponding QOL function.

Results

The mean age of the 875 non-metastatic NPC patients was 50.3 years. The estimated average LE and QALE for NPC patients and for the reference population were 15.5 years and 14.3 quality-adjusted life years (QALYs) and 29.5 years and 29.5 QALYs, respectively. On average, the estimated lifelong duration of pain and painkiller use were 6.0 years and 2.2 years. The estimated lifelong duration of impairment of swallowing, speech, smell and taste were 14.0, 9.8, 8.7, and 7.5 years, respectively. The estimated lifelong duration of problems with dry mouth, teeth, emotion, fatigue, sleep, and social contact were 13.4, 10.1, 9.1, 12.3, 6.7, and 4.5 years, respectively. The estimated lifelong duration of tube-feeding was 1.3 months.

Conclusions

The estimated LE and QALE for NPC patients were 15.5 years and 14.3 QALYs. Furthermore, SWPS could help people understand more about the impact of radiotherapy on NPC patients. These data could also be useful for policy makers to allocate limited resources in health care.
The Role of Platelet Cell Surface P-Selectin for the Direct Platelet-Tumor Cell Contact During Metastasis Formation in Human Tumors
Authors: Fabricius Hans-Åke , Starzonek Sarah , Lange Tobias
Published: March 2021

Mammalian platelets, devoid of nuclei, are the smallest cells in the blood stream. They are essential for hemostasis, but also transmit cell signals that are necessary for regenerative and generative processes such as inflammation, immunity and tissue repair. In particular, in malignancies they are also associated with cell proliferation, angiogenesis, and epithelial-mesenchymal transition. Platelets promote metastasis and resistance to anti-tumor treatment. However, fundamental principles of the interaction between them and target cells within tumors are complex and still quite obscure. When injected into animals or circulating in the blood of cancer patients, cancer cells ligate platelets in a timely manner closely related to platelet activation either by direct contact or by cell-derived substances or microvesicles. In this context, a large number of different surface molecules and transduction mechanisms have been identified, although the results are sometimes species-specific and not always valid to humans. In this mini-review, we briefly summarize the current knowledge on the role of the direct and indirect platelet-tumor interaction for single steps of the metastatic cascade and specifically focus on the functional role of P-selectin.
Adherence and Associated Factors of Treatment Regimen in Drug-Susceptible Tuberculosis Patients
Authors: Bea Sungho , Lee Hyesung , Kim Ju Hwan , Jang Seung Hun , Son Hyunjin , Kwon Jin-Won , Shin Ju-Young
Published: March 2021

Background: Adherence to tuberculosis (TB) drugs is one of the key aspects of global TB control, yet there is a lack of epidemiological evidence on the factors influencing adherence to TB drugs. Thus, this study aimed to explore the adherence and factors associated with adherence among TB patients in South Korea.

Methods: We conducted a cohort study using a sampled national healthcare database from 2017 to 2018. Our study population included incident TB patients initiating quadruple or triple regimen who were available for follow-up for 180-days. Adherence was evaluated using the proportion of days covered (PDC): 1) adherent group: patients with PDC ≥80%; 2) non-adherent group: patients with PDC <80%. Kaplan-Meier analysis was conducted to calculate the median time-to-discontinuation in the study population. We calculated the adjusted odds ratios (aOR) with 95% confidence intervals (CI) to assess factors associated with adherence to TB drugs using logistic regression.

Results: Of 987 patients, 558 (56.5%) were adherent and 429 (43.5%) were non-adherent, with the overall mean PDC of 68.87% (standard deviation, 33.37%). The median time-to-discontinuation was 113 days (interquartile range 96–136) in the study population. Patients initiating quadruple regimen were more likely to adhere in comparison to the triple regimen (aOR 4.14; 95% CI 2.78–6.17), while those aged ≥65 years (aOR 0.53; 95% CI 0.35–0.81), with a history of dementia (aOR 0.53; 95% CI 0.34–0.85), and with history of diabetes mellitus (aOR 0.70; 95% CI 0.52–0.96) were less likely to adhere to the drug.

Conclusion: Approximately 45% of TB patients were non-adherent to the drug, which is a major concern for the treatment outcome. We call for intensified attention from the authorities and healthcare providers to reinforce patients’ adherence to the prescribed TB drugs.
The UK Government’s COVID-19 Policy: What Does “Guided by the Science” Mean in Practice?
Authors: Cairney Paul
Published: March 2021

UK government ministers state that their COVID-19 policy is “guided by the science.” In practice they mean “our scientists,” and initial UK government policy was highly consistent with that advice. Ministers formed strong relationships with key scientific advisors, relied on evidence from their Scientific Advisory Group for Emergencies (SAGE), and ignored or excluded many other sources. I explore two types of lesson from this experience. First, UK studies of interest groups help explain the politics of expert advice. They show that the minister-adviser relationship is conditional on the ways in which the UK government assigns status to particular sources of science advice, and the willingness of those advisers to follow the “rules of the game,” within a wider political and policymaking context. Second, documentary analysis of SAGE minutes and meeting papers, and analysis of oral evidence to key House of Commons committees, shows high consistency between SAGE advice and UK government policy in the run up to lockdown. Ministers relied on their advisers to define the policy problem and identify feasible solutions throughout this period, while their advisors supported government policy and the right of ministers to make it. This new experience reflects and reinforces longstanding evidence from policy community studies: some experts remain core insiders if they advise on policies that they do not necessarily support, while outsiders have the freedom to criticize the policy they were unable to influence.
Co-designing Behavior Change Resources With Treatment-Seeking Smokers: Engagement Events' Findings
Authors: Minian Nadia , Lingam Mathangee , deRuiter Wayne K. , Dragonetti Rosa , Selby Peter
Published: March 2021

Background: Primary care organizations are well-suited to help patients change their unhealthy behaviors. Evidence shows that risk communication and self-monitoring of behavior are is an effective strategy practitioners can use to promote health behavior change with their patients. In order for this evidence to be actionable, it is important to understand how patients would like this information to be communicated and to operationalize the self-monitoring resources. The objective of this study was to co-create resources that encourage behavior change based on the scientific evidence and from patients with lived experiences.

Materials and Methods: Twenty-seven individuals who participated in a smoking cessation program and engaged in at least one other unhealthy behavior joined one of two engagement events. Each event was 3 h in duration and consisted of two exercises that provided support to participants in reaching a consensus about the types of messages they would like to receive from their practitioner as well as self-monitoring resources they would prefer to use. The first exercise followed an adapted version of the Consensus Methodology developed by the Institute of Cultural Affairs Canada, while the second exercise was in accordance to the Nominal Group Technique.

Results: Participants' preference was to have practitioners convey messages to promote health behavior change that include positive affirmation and to monitor all their health behaviors using a single self-reported tracking sheet.

Conclusions: This paper features the use of engagement events to reflect upon and identify potential resources that treatment seeking smokers prefer to receive while attempting to modify unhealthy behaviors. These resources can be used by health care providers in primary care settings to support health promotion interventions and assist their patients to increase their likelihood of adopting positive changes to risk behaviors.
Co-creating Virtual Reality Interventions for Alcohol Prevention: Living Lab vs. Co-design
Authors: Dietrich Timo , Guldager Julie Dalgaard , Lyk Patricia , Vallentin-Holbech Lotte , Rundle-Thiele Sharyn , Majgaard Gunver , Stock Christiane
Published: March 2021

Addressing the need for collaborative involvement in health intervention design requires application of processes that researchers and practitioners can apply confidently to actively involve end-users and wider stakeholder groups. Co-creation enables participation by focusing on empowering a range of stakeholders with opportunities to influence the final intervention design. While collaboration with users and stakeholders during intervention design processes are considered vital, clear articulation of procedures and considerations for various co-creation methodologies warrants further research attention. This paper is based on two case studies conducted in Australia and Denmark where researchers co-created virtual reality interventions in an alcohol prevention context. This paper explored and reflected on two co-creation methods–co-design and the Living Lab—and showcased the different processes and procedures of each approach. The study demonstrates that both approaches have merit, yet highlights tensions in distinguishing between the application of each of the respective steps undertaken in each of the processes. While a lot of similarities exist between approaches, differences are evident. Overall, it can be said that the Living Lab is broader in scope and processes applied within the Living Labs approach are more abstract. The co-design process that we applied in the first case study is described more granularly delivering a clear a step-by-step guide that practitioners can implement to co-design solutions that end-users value and that stakeholders support. An agenda to guide future research is outlined challenging researchers to identify the most effective co-creation approach.
Working Out Your Pain: Why Intense Exercise Is Painful
Authors: Berger Marcel , Henning Daniel , Hout Michael C.
Published: March 2021

When it comes to experiencing pain, most people will agree that it is an uncomfortable sensation that we would rather avoid. Pain can vary in intensity—ranging from the mild sensation of stubbing your toe to the intense pain of a broken bone—and we generally think of it as a bad thing. But pain can be thought of in two ways: sometimes it is a warning signal that something is wrong with our bodies, but other times it is benign, meaning it is not an indication that something is necessarily wrong. Warning-signal pain occurs when certain areas of your body get hurt or experience tissue damage, like when a sibling accidentally closes the car door on your fingers. Benign pain, on the other hand, is the type of pain you feel during intense physical exercise, and as you will come to see, is not always something you need to avoid!
Narrow and Brittle or Broad and Nimble? Comparing Adaptive Capacity in Simplifying and Diversifying Farming Systems
Authors: Petersen-Rockney Margiana , Baur Patrick , Guzman Aidee , Bender S. Franz , Calo Adam , Castillo Federico , De Master Kathryn , Dumont Antoinette , Esquivel Kenzo , Kremen Claire , LaChance James , Mooshammer Maria , Ory Joanna , Price Mindy J. , Socolar Yvonne , Stanley Paige , Iles Alastair , Bowles Timothy
Published: March 2021

Humanity faces a triple threat of climate change, biodiversity loss, and global food insecurity. In response, increasing the general adaptive capacity of farming systems is essential. We identify two divergent strategies for building adaptive capacity.Simplifyingprocesses seek to narrowly maximize production by shifting the basis of agricultural production toward centralized control of socially and ecologically homogenized systems.Diversifyingprocesses cultivate social-ecological complexity in order to provide multiple ecosystem services, maintain management flexibility, and promote coordinated adaptation across levels. Through five primarily United States focused cases of distinct agricultural challenges—foodborne pathogens, drought, marginal lands, labor availability, and land access and tenure—we compare simplifying and diversifying responses to assess how these pathways differentially enhance or degrade the adaptive capacity of farming systems in the context of the triple threat. These cases show that diversifying processes can weave a form of broad and nimble adaptive capacity that is fundamentally distinct from the narrow and brittle adaptive capacity produced through simplification. We find that while there are structural limitations and tradeoffs to diversifying processes, adaptive capacity can be facilitated by empowering people and enhancing ecosystem functionality to proactively distribute resources and knowledge where needed and to nimbly respond to changing circumstances. Our cases suggest that, in order to garner the most adaptive benefits from diversification, farming systems should balance the pursuit of multiple goals, which in turn requires an inclusive process for active dialogue and negotiation among diverse perspectives. Instead of locking farming systems into pernicious cycles that reproduce social and ecological externalities, diversification processes can enable nimble responses to a broad spectrum of possible stressors and shocks, while also promoting social equity and ecological sustainability.
Biofilm Formation in Xanthomonas arboricola pv. pruni: Structure and Development
Authors: Sabuquillo Pilar , Cubero Jaime
Published: March 2021

Xanthomonasarboricola pv. pruni (Xap) causes bacterial spot of stone fruit and almond, an important plant disease with a high economic impact. Biofilm formation is one of the mechanisms that microbial communities use to adapt to environmental changes and to survive and colonize plants. Herein, biofilm formation by Xap was analyzed on abiotic and biotic surfaces using different microscopy techniques which allowed characterization of the different biofilm stages compared to the planktonic condition. All Xap strains assayed were able to form real biofilms creating organized structures comprised by viable cells. Xap in biofilms differentiated from free-living bacteria forming complex matrix-encased multicellular structures which become surrounded by a network of extracellular polymeric substances (EPS). Moreover, nutrient content of the environment and bacterial growth have been shown as key factors for biofilm formation and its development. Besides, this is the first work where different cell structures involved in bacterial attachment and aggregation have been identified during Xap biofilm progression. Our findings provide insights regarding different aspects of the biofilm formation of Xap which improve our understanding of the bacterial infection process occurred in Prunus spp and that may help in future disease control approaches.
Irrigation Timing as a Practice of Effective Weed Management in Established Alfalfa (Medicago sativa L.) Crop
Authors: Kanatas Panagiotis , Gazoulis Ioannis , Travlos Ilias
Published: March 2021

Irrigation is an agronomic practice of major importance in alfalfa (Medicago sativa L), especially in the semiarid environments of Southern Europe. Field experimentation was conducted in Western Greece (2016–2018) to evaluate the effects of irrigation timing on weed presence, alfalfa yield performance, and forage quality. In a randomized complete block design (four replications), two cultivars (“Ypati 84” and “Hyliki”) were the main plots, while three irrigation timings were the subplots (split-plot). The irrigation timings were IT-1, IT-2, and IT-3, denoting irrigation 1 week before harvest, 1 week after harvest, and 2 weeks after harvest, respectively. IT-1 reduced Solanum nigrum L. density by 54% and 79% as compared to IT-3 and IT-2, respectively. Chenopodium album L. density was the highest under IT-2. IT-3 resulted in 41% lower Amaranthus retroflexus L. density in comparison to IT-2, while the lowest values were observed under IT-1. Stand density and stems·plant−1 varied between years (p ≤ 0.05). Mass·stem−1 and alfalfa forage yield were affected by the irrigation timings (p ≤ 0.001). Total weed density and forage yield were negatively correlated in both the second (R2 = 87.013%) and the fourth (R2 = 82.691%) harvests. IT-1 and IT-3 increased forage yield, leaf per stem ratio, and crude protein as compared to IT-2. Further research is required to utilize the use of cultural practices for weed management in perennial forages under different soil and climatic conditions.
Analysis of the Productivity, Immunity, and Health Performance of Nile Tilapia (Oreochromis niloticus) Broodstock-fed Dietary Fermented Extracts Sourced from Saccharomyces cerevisiae (Hilyses): A Field Trial
Authors: Abu-Elala Nermeen M. , Ali Tamer El-Sayed , Ragaa Naela M. , Ali Sara E. , Abd-Elsalam Reham M. , Younis Nehal A. , Abdel-Moneam Dalia A. , Hamdien Aya H. , Bonato Melina , Dawood Mahmoud A.O.
Published: March 2021

The present study aimed to evaluate the effect of dietary fermented extracts sourced from Saccharomyces cerevisiae (nucleotides, β-glucans and MOS) (Hilyses®) on the production and health of Nile tilapia (Oreochromis niloticus) broodstock, as well as on seed survival and performance. The trial was performed in a hatchery along the spawning season and continued in the laboratory to monitor the performance in fry and fingerlings. The broodstock were divided into two groups, (C) fed a basal diet and (H) fed 0.4% Hilyses. Blood and histological parameters, antioxidant power, cortisol level and the expression of some immune-related (TLR-2, IL-1β and TNF-α) and growth-related genes (MUC-2 and IGF-1) were measured. The obtained seeds were subdivided into four treatments: (C-C) fed a basal diet, (C-H) fed 0.4% Hilyses, (H-C) fed a basal diet and (H-H) fed 0.4% Hilyses. Results revealed that the dietary inclusion of Hilyses in the broodstock increased seed production, survival, hematological parameters, and antioxidant power. Moreover, it improved the intestinal microstructure and upregulated the immune- and growth-related genes. The growth indices of fry and fingerlings were significantly increased in all Hilyses-treated groups (p < 0.05). The performance in the (H-H) group significantly surpassed those of all groups. Therefore, dietary fermented yeast could be used as a strategic solution to sustain tilapia production.
Impact of Overuse and Sexually Transmitted Infections on Seminal Parameters of Extensively Managed Bulls
Authors: Montoya-Monsalve Giovanni , Sánchez-Calabuig María-Jesús , Blanco-Murcia Javier , Elvira Laura , Gutiérrez-Adán Alfonso , Ramos-Ibeas Priscila
Published: March 2021

Natural service remains the main breeding method in extensively managed beef herds. Although the bull might be the most important factor in determining herd fertility, its importance has been largely overlooked, focusing instead on female fertility. Management of the bull is critical to maximize the opportunities for cow conception. Infectious bovine rhinotracheitis (IBR) and bovine viral diarrhea (BVD) are infections associated with reduced conception rates. This study aimed to determine the effect of both IBR and BVD infection, and bull: cow ratio on seminal parameters in the bull and herd fertility. The presence of antibodies to IBR and BVD, seminal parameters (volume, concentration, mass, and progressive motility), and herd fertility were analyzed in 158 extensively managed bulls. Sperm concentration and mass motility, as well as herd fertility, were significantly lower in BVD-positive bulls. No significant differences were found between IBR-positive and -negative bulls in any reproductive parameter. Sperm concentration was negatively affected by BVD infection in both Charolais and Limousin bulls, whereas mass motility and herd fertility were reduced in Limousin bulls only. No differences were observed in the cow: bull ratio between BVD+ and BVD- bulls. A significant negative correlation was detected between the number of cows per bull and herd fertility, which was negatively affected when herds had more than 40 cows per bull. In conclusion, BVD and bull overuse negatively affect the reproductive performance of the herd.
A Novel ALDH2 Activator AD-9308 Improves Diastolic and Systolic Myocardial Functions in Streptozotocin-Induced Diabetic Mice
Authors: Lee Hsiao-Lin , Hee Siow-Wey , Hsuan Chin-Feng , Yang Wenjin , Huang Jing-Yong , Lin Ya-Ling , Hsu Chih-Neng , Hwang Juey-Jen , Chen Shiau-Mei , Ding Zhi-Zhong , Lee Tung-Yuan , Lin Yu-Chiao , Tsai Feng-Chiao , Su Wei-Lun , Chueh Li-Yun , Hsieh Meng-Lun , Chen Che-Hong , Mochly-Rosen Daria , Chang Yi-Cheng , Chuang Lee-Ming
Published: March 2021

Diabetes mellitus has reached epidemic proportion worldwide. One of the diabetic complications is cardiomyopathy, characterized by early left ventricular (LV) diastolic dysfunction, followed by development of systolic dysfunction and ventricular dilation at a late stage. The pathogenesis is multifactorial, and there is no effective treatment yet. In recent years, 4-hydroxy-2-nonenal (4-HNE), a toxic aldehyde generated from lipid peroxidation, is implicated in the pathogenesis of cardiovascular diseases. Its high bioreactivity toward proteins results in cellular damage. Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is the major enzyme that detoxifies 4-HNE. The development of small-molecule ALDH2 activator provides an opportunity for treating diabetic cardiomyopathy. This study found that AD-9308, a water-soluble andhighly selective ALDH2 activator, can improve LV diastolic and systolic functions, and wall remodeling in streptozotocin-induced diabetic mice. AD-9308 treatment dose-dependently lowered serum 4-HNE levels and 4-HNE protein adducts in cardiac tissue from diabetic mice, accompanied with ameliorated myocardial fibrosis, inflammation, and apoptosis. Improvements of mitochondrial functions, sarco/endoplasmic reticulumcalcium handling and autophagy regulation were also observed in diabetic mice with AD-9308 treatment. In conclusion, ADLH2 activation effectively ameliorated diabetic cardiomyopathy, which may be mediated through detoxification of 4-HNE. Our findings highlighted the therapeutic potential of ALDH2 activation for treating diabetic cardiomyopathy.
Empirical Kinetic Modelling and Mechanisms of Quercetin Thermal Degradation in Aqueous Model Systems: Effect of pH and Addition of Antioxidants
Authors: Kellil Abdessamie , Grigorakis Spyros , Loupassaki Sofia , Makris Dimitris P.
Published: March 2021

Quercetin (Qt) is a natural flavonoid of high biological significance, and it occurs in a wide variety of plant foods. Although its oxidation by various means has been extensively studied, its behavior with regard to thermal treatments remains a challenge. The study described herein aimed at investigating Qt thermal decomposition, by proposing an empirical sigmoidal model for tracing degradation kinetics. This model was employed to examine the effect of addition of antioxidants on Qt thermal degradation, including ascorbic acid, L-cysteine, and sulfite. Furthermore, degradation pathways were proposed by performing liquid chromatography-tandem mass spectrometry analyses. Upon addition of any antioxidant used, the sigmoidal course of Qt thermal degradation was pronounced, evidencing the validity of the empirical model used in the study of similar cases. The antioxidants retarded Qt degradation in a manner that appeared to depend on Qt/antioxidant molar ratio. No major differentiation in the degradation mechanism was observed in response to the addition of various antioxidants, and in all cases protocatechuic acid and phloroglucinol carboxylic acid were typical degradation products identified. Furthermore, in all cases tested the solutions resulted after thermal treatment possessed inferior antioxidant properties compared to the initial Qt solutions, and this demonstrated the detrimental effects of heating on Qt. The empirical model proposed could be of assistance in interpreting the degradation behavior of other polyphenols, but its validity merits further investigation.
Polylactic Acid/Carbon Nanoparticle Composite Filaments for Sensing
Authors: Silva Mariana M. , Lopes Paulo E. , Li Yilong , Pötschke Petra , Ferreira Fernando N. , Paiva Maria C.
Published: March 2021

Polylactic acid (PLA) is a bio-based, biodegradable polymer that presents high potential for biomedical and sensing applications. Ongoing works reported in the literature concern mainly applications based on 3D printing, while textile applications are hindered by the limited flexibility of PLA and its composite filaments. In the present work, PLA/multiwall carbon nanotube (MWCNT) composite filaments were produced with enhanced flexibility and electrical conductivity, which may be applied on a textile structure. A biodegradable plasticizer was incorporated in the nanocomposites, aiming at improving MWCNT dispersion and increasing the flexibility of the filaments. Filaments were produced with a range of compositions and their morphology was characterized as well as their thermal, thermomechanical, and electrical properties. Selected compositions were tested for sensing activity using saturated acetone vapor, demonstrating a suitable response and potential for the application in fabrics with sensing capacity.
Strain Sensitivity Enhancement of Broadband Ultrasonic Signals in Plates Using Spectral Phase Filtering
Authors: Martinho Lucas M. , Kubrusly Alan C. , Pérez Nicolás , von der Weid Jean Pierre
Published: March 2021

The focused signal obtained by the time-reversal or the cross-correlation techniques of ultrasonic guided waves in plates changes when the medium is subject to strain, which can be used to monitor the medium strain level. In this paper, the sensitivity to strain of cross-correlated signals is enhanced by a post-processing filtering procedure aiming to preserve only strain-sensitive spectrum components. Two different strategies were adopted, based on the phase of either the Fourier transform or the short-time Fourier transform. Both use prior knowledge of the system impulse response at some strain level. The technique was evaluated in an aluminum plate, effectively providing up to twice higher sensitivity to strain. The sensitivity increase depends on a phase threshold parameter used in the filtering process. Its performance was assessed based on the sensitivity gain, the loss of energy concentration capability, and the value of the foreknown strain. Signals synthesized with the time–frequency representation, through the short-time Fourier transform, provided a better tradeoff between sensitivity gain and loss of energy concentration.
Sensitivity and Uncertainty Analyses of Human and Organizational Risks in Fire Safety Systems for High-Rise Residential Buildings with Probabilistic T-H-O-Risk Methodology
Authors: Tan Samson , Weinert Darryl , Joseph Paul , Moinuddin Khalid
Published: March 2021

Given that existing fire risk models often ignore human and organizational errors (HOEs) ultimately leading to underestimation of risks by as much as 80%, this study employs a technical-human-organizational risk (T-H-O-Risk) methodology to address knowledge gaps in current state-of-the-art probabilistic risk analysis (PRA) for high-rise residential buildings with the following goals: (1) Develop an improved PRA methodology to address concerns that deterministic, fire engineering approaches significantly underestimate safety levels that lead to inaccurate fire safety levels. (2) Enhance existing fire safety verification methods by incorporating probabilistic risk approach and HOEs for (i) a more inclusive view of risk, and (ii) to overcome the deterministic nature of current verification methods. (3) Perform comprehensive sensitivity and uncertainty analyses to address uncertainties in numerical estimates used in fault tree/event trees, Bayesian network and system dynamics and their propagation in a probabilistic model. (4) Quantification of human and organizational risks for high-rise residential buildings which contributes towards a policy agenda in the direction of a sustainable, risk-based regulatory regime. This research contributes to the development of the next-generation building codes and risk assessment methodologies.
Biofuels from Micro-Organisms: Thermodynamic Considerations on the Role of Electrochemical Potential on Micro-Organisms Growth
Authors: Lucia Umberto , Grisolia Giulia
Published: March 2021

Biofuels from micro-organisms represents a possible response to the carbon dioxide mitigation. One open problem is to improve their productivity, in terms of biofuels production. To do so, an improvement of the present model of growth and production is required. However, this implies an understanding of the growth spontaneous conditions of the bacteria. In this paper, a thermodynamic approach is developed in order to highlight the fundamental role of the electrochemical potential in bacteria proliferation. Temperature effect on the biosystem behaviour has been pointed out. The results link together the electrochemical potential, the membrane electric potential, the pH gradient through the membrane, and the temperature, with the result of improving the thermodynamic approaches, usually introduced in this topic of research.
Study of the Hemodynamics Effects of an Isolated Systolic Hypertension (ISH) Condition on Cerebral Aneurysms Models, Using FSI Simulations
Authors: Barahona José , Valencia Alvaro , Torres María
Published: March 2021

Hemodynamics is recognized as a relevant factor in the development and rupture of cerebral aneurysms, so further studies related to different physiological conditions in human represent an advance in understanding the pathology and rupture risk. In this paper, Fluid-structure interaction simulations (FSI) were carried out in six models of cerebral aneurysms, in order to study the hemodynamics effects of an isolated systolic hypertension (ISH) condition and compare it to a normal or normotensive pressure condition and a higher hypertension condition. Interestingly, the ISH condition showed, in general, the greatest hemodynamics changes, evidenced in the Time-Averaged Wall Shear Stress (TAWSS), Oscillatory Shear Index (OSI), and Relative Residence Time (RRT) parameters, with respect to a normal condition. These results could imply that a not high-pressure condition (ISH), characterized with a different shape and an abrupt change in its diastolic and systolic range may present more adverse hemodynamic changes compared to a higher-pressure condition (such as a hypertensive condition) and therefore have a greater incidence on the arterial wall remodeling and rupture risk.
Automated Optical Inspection System for O-Ring Based on Photometric Stereo and Machine Vision
Authors: Yang Fu-Sheng , Ho Chao-Ching , Chen Liang-Chia
Published: March 2021

This research developed an AOI (automated optical inspection) system for the O-Ring inspection. First, an AOI system was implemented to detect surface scratches, flow marks, non-fills, and indentations on elastomer O-Rings with high surface reflection coefficients. The proposed system employed multiple light source structures to realize the photometric stereo. This method eased the identification of the O-Ring contour and Bézier control points. Then, by applying an interpolation process on these control points, we estimated the paths of the object surface. Simultaneously, regression analysis was conducted to produce a new smooth surface and then a constructed surface was compared with the model built by the photometric stereo method. The difference was deemed the candidate defect location. Overall, the detection recall rate was 100% and accuracy reached 96.56%. This paper also developed an AOI system for the O-Ring dimension measurement. The system analyzed the contour of the O-Ring and reversely calculated the Bézier curve control points. Then, those control points were used with De Casteljau’s algorithm to estimate the O-Ring dimension with high accuracy.
Kinematic Modelling and Motion Analysis of a Humanoid Torso Mechanism
Authors: Russo Matteo , Ceccarelli Marco , Cafolla Daniele
Published: March 2021

This paper introduces a novel kinematic model for a tendon-driven compliant torso mechanism for humanoid robots, which describes the complex behaviour of a system characterised by the interaction of a complex compliant element with rigid bodies and actuation tendons. Inspired by a human spine, the proposed mechanism is based on a flexible backbone whose shape is controlled by two pairs of antagonistic tendons. First, the structure is analysed to identify the main modes of motion. Then, a constant curvature kinematic model is extended to describe the behaviour of the torso mechanism under examination, which includes axial elongation/compression and torsion in addition to the main bending motion. A linearised stiffness model is also formulated to estimate the static response of the backbone. The novel model is used to evaluate the workspace of an example mechanical design, and then it is mapped onto a controller to validate the results with an experimental test on a prototype. By replacing a previous approximated model calibrated on experimental data, this kinematic model improves the accuracy and efficiency of the torso mechanism and enables the performance evaluation of the robot over the reachable workspace, to ensure that the tendon-driven architecture operates within its wrench-closure workspace.