bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk Signature of Cancer-Associated Fibroblast–Secreted Cytokines Associates With Clinical Outcomes of Breast Cancer
Authors: Sun Chunxiao , Wang Siwei , Zhang Yuchen , Yang Fan , Zeng Tianyu , Meng Fanchen , Yang Mengzhu , Yang Yiqi , Hua Yijia , Fu Ziyi , Li Jun , Huang Xiang , Wu Hao , Yin Yongmei , Li Wei
Published: July 2021

Cancer-associated fibroblasts (CAFs) are key components in tumor microenvironment (TME). The secreted products of CAFs play important roles in regulating tumor cells and further impacting clinical prognosis. This study aims to reveal the relationship between CAF-secreted cytokines and breast cancer (BC) by constructing the risk signature. We performed three algorithms to reveal CAF-related cytokines in the TCGA BC dataset and identified five prognosis-related cytokines. Then we used single-cell RNA sequencing (ScRNA-Seq) datasets of BC to confirm the expression level of these five cytokines in CAFs. METABRIC and other independent datasets were utilized to validate the findings in further analyses. Based on the identified five-cytokine signature derived from CAFs, BC patients with high-risk score (RS) had shorter overall survival than low-RS cases. Further analysis suggested that the high-RS level correlated with cell proliferation and mast cell infiltration in BCs of the Basal-like subtype. The results also indicated that the level of RS could discriminate the high-risk BC cases harboring driver mutations (i.e., PI3KCA, CDH1, and TP53). Additionally, the status of five-cytokine signature was associated with the frequency and molecular timing of whole genome duplication (WGD) events. Intratumor heterogeneity (ITH) analysis among BC samples indicated that the high-RS level was associated with the increase of tumor subclones. This work demonstrated that the prognostic signature based on CAF-secreted cytokines was associated with clinical outcome, tumor progression, and genetic alteration. Our findings may provide insights to develop novel strategies for early intervention and prognostic prediction of BC.
CK-3, A Novel Methsulfonyl Pyridine Derivative, Suppresses Hepatocellular Carcinoma Proliferation and Invasion by Blocking the PI3K/AKT/mTOR and MAPK/ERK Pathways
Authors: Wu Qiong , Liu Tian-yi , Hu Bai-chun , Li Xiang , Wu Yu-ting , Sun Xiao-tong , Jiang Xiao-wen , Wang Shu , Qin Xiao-chun , Ding Huai-wei , Zhao Qing-chun
Published: July 2021

Hepatocellular carcinoma (HCC) is an aggressive tumor with a poor prognosis that highly expresses phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (ERK). The PI3K/AKT/mTOR and MAPK/ERK signaling pathways play a crucial role in HCC tumor formation, cell cycle, apoptosis and survival. However, no effective targeted therapies against these pathways is available, mainly due to the extensive and complex negative feedback loops between them. Here we used CK-3, a dual blocker of the PI3K/AKT/mTOR and MAPK/ERK pathways, against HCC cell lines to verify its anti-tumor activity in vitro. CK-3 exhibited cytotoxic activity against HCC, as demonstrated with MTT and colony formation assays. The anti-metastatic potential of CK-3 was demonstrated with wound healing and cell invasion assays. The ability of CK-3 to block both the PI3K/AKT/mTOR and MAPK/ERK pathways was also confirmed. CK-3 induced the apoptosis of Hep3B cells, while Bel7402 cells died via mitotic catastrophe (MC). Oral administration of CK-3 also inhibited the subcutaneous growth of BEL7402 cells in nude mice. Simultaneous PI3K/AKT/mTOR and MAPK/ERK pathway inhibition with CK-3 may be superior to single pathway monotherapies by inhibiting their feedback-regulation, and represents a potential treatment for HCC.
Adipose Stromal Cell-Secretome Counteracts Profibrotic Signals From IPF Lung Matrices
Authors: Vasse Gwenda F. , Van Os Lisette , De Jager Marina , Jonker Marnix R. , Borghuis Theo , Van Den Toorn L. Tim , Jellema Pytrick , White Eric S. , Van Rijn Patrick , Harmsen Martin C. , Heijink Irene H. , Melgert Barbro N. , Burgess Janette K.
Published: July 2021

Introduction: Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease characterized by excess deposition and altered structure of extracellular matrix (ECM) in the lungs. The fibrotic ECM is paramount in directing resident cells toward a profibrotic phenotype. Collagens, an important part of the fibrotic ECM, have been shown to be structurally different in IPF. To further understand the disease to develop better treatments, the signals from the ECM that drive fibrosis need to be identified. Adipose tissue-derived stromal cell conditioned medium (ASC-CM) has demonstrated antifibrotic effects in animal studies but has not been tested in human samples yet. In this study, the collagen structural integrity in (fibrotic) lung tissue, its interactions with fibroblasts and effects of ASC-CM treatment hereon were studied.

Methods: Native and decellularized lung tissue from patients with IPF and controls were stained for denatured collagen using a collagen hybridizing peptide. Primary lung fibroblasts were seeded into decellularized matrices from IPF and control subjects and cultured for 7 days in the presence or absence of ASC-CM. Reseeded matrices were fixed, stained and analyzed for total tissue deposition and specific protein expression.

Results: In both native and decellularized lung tissue, more denatured collagen was observed in IPF tissue compared to control tissue. Upon recellularization with fibroblasts, the presence of denatured collagen was equalized in IPF and control matrices, whereas total ECM was higher in IPF matrices than in the control. Treatment with ASC-CM resulted in less ECM deposition, but did not alter the levels of denatured collagen.

Discussion: Our data showed that ASC-CM can inhibit fibrotic ECM-induced profibrotic behavior of fibroblasts. This process was independent of collagen structural integrity. Our findings open up new avenues for ASC-CM to be explored as treatment for IPF.
Ten Rules for Conducting Retrospective Pharmacoepidemiological Analyses: Example COVID-19 Study
Authors: Powell Michael , Koenecke Allison , Byrd James Brian , Nishimura Akihiko , Konig Maximilian F. , Xiong Ruoxuan , Mahmood Sadiqa , Mucaj Vera , Bettegowda Chetan , Rose Liam , Tamang Suzanne , Sacarny Adam , Caffo Brian , Athey Susan , Stuart Elizabeth A. , Vogelstein Joshua T.
Published: July 2021

Since the beginning of the COVID-19 pandemic, pharmaceutical treatment hypotheses have abounded, each requiring careful evaluation. A randomized controlled trial generally provides the most credible evaluation of a treatment, but the efficiency and effectiveness of the trial depend on the existing evidence supporting the treatment. The researcher must therefore compile a body of evidence justifying the use of time and resources to further investigate a treatment hypothesis in a trial. An observational study can provide this evidence, but the lack of randomized exposure and the researcher’s inability to control treatment administration and data collection introduce significant challenges. A proper analysis of observational health care data thus requires contributions from experts in a diverse set of topics ranging from epidemiology and causal analysis to relevant medical specialties and data sources. Here we summarize these contributions as 10 rules that serve as an end-to-end introduction to retrospective pharmacoepidemiological analyses of observational health care data using a running example of a hypothetical COVID-19 study. A detailed supplement presents a practical how-to guide for following each rule. When carefully designed and properly executed, a retrospective pharmacoepidemiological analysis framed around these rules will inform the decisions of whether and how to investigate a treatment hypothesis in a randomized controlled trial. This work has important implications for any future pandemic by prescribing what we can and should do while the world waits for global vaccine distribution.
Atrial Natriuretic Peptide Inhibited ABCA1/G1-dependent Cholesterol Efflux Related to Low HDL-C in Hypertensive Pregnant Patients
Authors: Dong Yubing , Lin Yi , Liu Wanyu , Zhang Wei , Jiang Yinong , Song Wei
Published: July 2021

Objective: It has been reported that atrial natriuretic peptide (ANP) regulates lipid metabolism by stimulating adipocyte browning, lipolysis, and lipid oxidation, and by impacting the secretion of adipokines. In our previous study, we found that the plasma ANP concentration of hypertensive disorders of pregnancy (HDP) was significantly increased in comparison to that of normotensive pregnancy patients. Thus, this study’s objective was to investigate the lipid profile in patients with HDP and determine the effects of ANP on the cholesterol efflux in THP-1 macrophages.

Methods: A total of 265 HDP patients and 178 normotensive women as the control group were recruited. Clinical demographic characteristics and laboratory profile data were collected. Plasma total triglycerides (TGs), total cholesterol (TC), low-density cholesterol (LDL-C), and high-density cholesterol (HDL-C) were compared between the two groups. THP-1 monocytes were incubated with different concentrations of ANP. ATP-binding cassette transporter A1 (ABCA1) and ATP-binding cassette transporter G1 (ABCG1) mRNA and protein were evaluated. ABCA1- and ABCG1-mediated cholesterol efflux to apolipoprotein A-Ⅰ (apoA-Ⅰ) and HDL, respectively, were measured by green fluorescent labeled NBD cholesterol. Natriuretic peptide receptor A (NPR-A) siRNA and specific agonists of the peroxisome proliferator–activated receptor-γ (PPAR-γ) and liver X receptor α (LXRα) were studied to investigate the mechanism involved.

Results: Plasma TG, TC, LDL-C, and LDL-C/HDL-C were significantly increased, and HDL-C was significantly decreased in the HDP group in comparison to the control (all p < 0.001). ANP inhibited the expression of ABCA1 and ABCG1 at both the mRNA and protein levels in a dose-dependent manner. The functions of ABCA1- and ABCG1-mediated cholesterol efflux to apoA-I and HDL were significantly decreased. NPR-A siRNA further confirmed that ANP binding to its receptor inhibited ABCA1/G1 expression through the PPAR-γ/LXRα pathway.

Conclusions: ABCA1/G1 was inhibited by the stimulation of ANP when combined with NPR-A through the PPAR-γ/LXRα pathway in THP-1 macrophages. The ABCA1/G1-mediated cholesterol efflux was also impaired by the stimulation of ANP. This may provide a new explanation for the decreased level of HDL-C in HDP patients.
A Review of Recent and Emerging Approaches for the Clinical Application of Cerenkov Luminescence Imaging
Authors: Mc Larney Benedict , Skubal Magdalena , Grimm Jan
Published: July 2021

Cerenkov luminescence is a blue-weighted emission of light produced by a vast array of clinically approved radioisotopes and LINAC accelerators. When β particles (emitted during the decay of radioisotopes) are present in a medium such as water or tissue, they are able to travel faster than the speed of light in that medium and in doing so polarize the molecules around them. Once the particle has left the local area, the polarized molecules relax and return to their baseline state releasing the additional energy as light (luminescence). This blue glow has commonly been used to determine the output of nuclear power plant cores and, in recent years, has found traction in the preclinical and clinical imaging field. This brief review will discuss the technology which has enabled the emergence of the biomedical Cerenkov imaging field, recent pre-clinical studies with potential clinical translation of Cerenkov luminescence imaging and the current clinical implementations of the method. Finally, an outlook is given as to the direction in which the field is heading.
Symbolic Convergence or Divergence? Making Sense of (the Rhetorical) Senses of a University-Wide Organizational Change
Authors: Ba Lina , Zhao W. G. Will
Published: July 2021

This research investigates the extent to which organizational change initiatives may lead to divergent patterns of sensemaking among organizational members. Drawing on the symbolic convergence theory, we performed an in-depth fantasy theme analysis of organization members’ rhetoric around an organizational change at a private university. Our analysis uncovers six fantasy themes and two corresponding fantasy types, which lead to no rhetorical vision. The lack of cognitive convergence between change initiators and change recipients suggests the inherent incompatibility between managerial and employee fantasies around organizational change, barring the exceptions of dual-responsibility change recipients (e.g., faculty members who also assume administrative responsibilities), who tend to adopt the change initiator rhetoric. Overall, this study informs our extant knowledge of change sensemaking with novel theoretical and methodological insights and bears implications for organizational change researchers and practitioners alike.
Parent-Child Dyadic Coping and Quality of Life in Chronically Diseased Children
Authors: Nap-van der Vlist Merel M. , van der Wal Reine C. , Grosfeld Eva , van de Putte Elise M. , Dalmeijer Geertje W. , Grootenhuis Martha A. , van der Ent Cornelis K. , van den Heuvel-Eibrink Marry M. , Swart Joost F. , Bodenmann Guy , Finkenauer Catrin , Nijhof Sanne L.
Published: July 2021

Different forms of dyadic coping are associated with positive outcomes in partner relationships, yet little is known about dyadic coping in parent-child relationships. The current research explored the association between parent-child dyadic coping and children’s quality of life in 12–18-year old children with a chronic disease (i.e., cystic fibrosis, autoimmune diseases, and children post-cancer treatment). In a sample of 105 parent-child dyads, self-reported forms of dyadic coping (i.e., stress communication, problem-oriented, emotion-oriented, and negative dyadic coping) and children’s quality of life were assessed. Children reported more stress communication and negative dyadic coping than their parents, while parents reported more problem-oriented dyadic coping and emotion-oriented dyadic coping than their children. More stress communication of the child was associated with more emotion-oriented dyadic coping and less negative dyadic coping of the parent. More negative dyadic coping of the child was associated with less stress communication, problem-oriented dyadic coping and emotion-oriented dyadic coping of the parent. Additionally, both children’s and parents’ negative dyadic coping were associated with lower self-reported pediatric quality of life and parents’ emotion-oriented dyadic coping was associated with higher pediatric quality of life. These findings emphasize that children and their parents mutually influence each other and that dyadic coping is associated with children’s quality of life. Theoretical and practical implications are discussed.
The Effects of Parenting and Temperament Similarity Among Adolescent Siblings on Positive Family Relationships
Authors: Shi Xinxin , Campione-Barr Nicole
Published: July 2021

The detrimental effects of parental differential treatment have been shown in previous research, but fewer researchers have pointed out that differential treatment does not always lead to negative outcomes. Thus, the present study examines the role of temperament similarity on the association between parenting similarity and positive family relationship qualities over 1 year in 145 adolescent sibling dyads (Mfirst−born = 14.97 and SD = 1.68 years; Msecond−born = 12.20 and SD = 1.92 years). Latent moderator structure models (LMS) showed that a higher level of parenting similarity was related to more positive family relationships when siblings were more similar in their temperaments; however, a lower level of parenting similarity was related to more positive relationship qualities with family members 1 year later in the context of less sibling temperament similarity.
“We Become a Madman to Be Calmed”—Patients’ Voices: Crossing the Threshold of Psychiatric Emergency Departments
Authors: Meriaux Mathilde , Denis Jennifer
Published: July 2021

Crossing the threshold of a psychiatric emergency room is a real ordeal. It is a passage that upsets, worries and sometimes paralyzes. However, it can also become an opportunity if psychological suffering is welcomed, accepted and understood. The welcome is the starting point for care. Our objective is to understand the meaning given to the phenomenon of “being welcomed” by patients experiencing psychiatric emergencies. The research is based on Grounded Theory Methodology (Glaser and Strauss, 1967) to explore and understand the complexity of the phenomenon. The results reveal that being welcomed can be considered as a rite of passage taking place in four successive phases, which are themselves organized into four interactive dimensions. The welcome as a rite of passage constitutes a powerful psychic support which arranges the transitional space in which the individual finds themself, and accompanies the identity transformations, the anguish, and the various sufferings which are not lacking in these moments of crisis.
Risk and Protective Factors for the Mental Health of Brazilian Healthcare Workers in the Frontline of COVID-19 Pandemic
Authors: Osório Flávia L. , Silveira Isabella Lara Machado , Pereira-Lima Karina , Crippa José Alexandre de Souza , Hallak Jaime Eduardo Cecílio , Zuardi Antônio Waldo , Loureiro Sonia Regina
Published: July 2021

The objective was to compare the mental health indicators of health workers providing care to individuals with COVID-19 in Brazil, considering sociodemographic and occupational variables and the risk perception of contamination by the Sars-CoV-2 of workers from different professions, identifying risk and protective factors. A sample of 916 health workers was assessed: physicians, nursing workers, and workers from other professions (psychologists, physical therapists, nutritionists, speech therapists, occupational therapists, dentists, pharmacists, and social workers). REDCAP software was used to collect data online, using standardized instruments to assess anxiety, depression, posttraumatic stress, and insomnia, and one questionnaire addressed risk and protective variables. Statistical techniques for comparing groups were used along with logistic regression analysis. The results revealed that all the groups presented indicators of significant mental health problems (>36%), especially the nursing group. A larger percentage of participants, regardless of the profession, presented a high rate of insomnia disorders, while posttraumatic stress was the least expressive. Occupational variables stand out as risk factors for mental health, with specificities among the different groups. A protective factor for all the groups was having positive professional prospects. The protective factors for the physicians group included support provided by co-workers, being older and a man, while being satisfied with physical protective measures implemented by the employing institution was a protective factor for the groups composed of nursing workers and other professionals. These findings are relevant for devising mental health care strategies.
Neurocognition Function of Patients With Bipolar Depression, Unipolar Depression, and Depression With Bipolarity
Authors: Lu Zhe , Wang Yingtan , Xun Guanglei
Published: July 2021

Much evidence shows that some Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5)-defined unipolar depression (UD) with bipolarity manifests bipolar diathesis. Little is known about the cognitive profiles of patients with depression with bipolarity (DWB). The study aimed to investigate the differences in cognitive profiles among patients with bipolar depression (BD), major depressive disorder (namely, UD), and DWB. Drug-naïve patients with BD, UD, and DWB and healthy controls (HC) were recruited (30 cases in each group). Cognitive function was evaluated by THINC-it (THINC-intelligent tool), Wisconsin Card Sorting Test (WCST), and continuous performance test (CPT). For THINC-it, no significant differences of the Z-scores in both objective and subjective factors were found between the DWB group and BD group, but the Z-scores in the BD group were significantly lower than those in the UD group. For WCST, significant differences were found between the BD group and DWB group in the number of responses, categories completed, trails to completed first category, perseverative responses, and perseverative errors. All the indices of WCST in the DWB group were significantly worse than those in the UD group except for trails to completed first category and total number of response correct. For CPT, only scores of leakage responses and false responses in the four-digit number in the BD group and DWB group were significantly higher than those in the UD group; no significant difference was found between the BD group and DWB group. The results indicated that patients with DWB might perform differently from those with UD but similarly to those with BD with cognition impairment.
From National Biosecurity Measures to Territorial ASF Preparedness: The Case of Free-Range Pig Farming in Corsica, France
Authors: Gisclard Marie , Charrier François , Trabucco Bastien , Casabianca François
Published: July 2021

In response to African swine fever (ASF) outbreaks in wild boars in Belgium in 2018, the French authorities issued national biosecurity measures for all pig farms, regardless of their geographical and socio-technical scale. Considering the Corsican pig farmers' demonstrations against these measures (for geographical, cultural, and economic reasons), this article questions the suitability of standardized top-down national measures that potentially endanger traditional breeding systems, which are increasingly marginalized in relation to the dominant industrial model. From an action-research approach, the article analyzes how local stakeholders go beyond usual classical biosecurity issues to propose a territorialized preparedness. Mediating between Corsican farmers and the government representatives, a technical committee made up of actors from various regional research and development bodies drew up a socially acceptable preparedness proposal. Viewing the health risk from a local standpoint, the committee provided arguments for maintaining the extensive grazing that is non-negotiable for the farmers, while getting the farmers to agree to change other practices (reproduction control) as a measure against health hazards already present. Analysis of the preparedness process and the mediation process shows that a territorialized bottom-up approach to the governance of health risks can make biosecurity measures more acceptable to farmers. It also points to the legitimacy of a set of alternatives to top-down measures that standardize farming systems and may lead to the disappearance of small farmers and their traditional systems.
Randomized Controlled Trial Comparing Autologous Protein Solution to Hyaluronic Acid Plus Triamcinolone for Treating Hip Osteoarthritis in Dogs
Authors: Franklin Samuel P. , Franklin Ashley L.
Published: July 2021

Twenty-three dogs with bilateral hip osteoarthritis were used to compare the efficacy of intra-articular injections of autologous protein solution (APS) to hyaluronic acid plus triamcinolone (HAT). Prior to treatment, owner assessments of pain and mobility were obtained using the canine brief pain inventory (CBPI) and Liverpool Osteoarthritis for Dogs (LOAD) questionnaires. Owners were also asked to list all medications used to control signs of pain associated with hip osteoarthritis (OA). In addition, objective kinetic data using a pressure sensitive walkway was used to quantify the relative weight bearing of each of the limbs (total pressure index; TPI). One hip was then selected using a random number generator for injection with HAT and the contralateral hip was injected with APS under the same sedation event. At 1-, 3-, and 6 months following injection, medication usage was recorded and dogs were re-assessed using the CBPI and LOAD questionnaires and using objective gait analysis to determine the TPI. Twenty dogs completed all aspects of the study and statistically significant (p < 0.05) improvements were noted by dog owners at every post-treatment time point in every category of pain and mobility as assessed by the CBPI and LOAD questionnaires. Only 5 dogs, compared to 14 pre-treatment, received any oral NSAID or other analgesic for the duration of the 6-month study period. The TPI, and change in TPI from baseline, were not statistically significantly different between the two treatments at any time point. These data suggest clinical efficacy of both APS and HAT, but fail to show superiority of one treatment vs. the other. The inability to detect a statistically significant difference between the two treatments could be attributable to a true lack of a difference, or a type II statistical error.
Recommendations for Ethical Review of Veterinary Clinical Trials
Authors: Bertout Jessica A. , Baneux Philippe J. R. , Robertson-Plouch Carol K.
Published: July 2021

Ethical review of both human and animal research is critical to ensuring that studies are conducted with due regard to the welfare and safety of enrolled subjects and to the integrity of the data. However, differences exist in laws, policies, and best practices between human and animal studies. Ethical review is required for most human studies. While the laws and standards are clear for humans and for laboratory animals, the laws and standards for clinical research for client-owned animals are not as well-defined. Here, we discuss gaps in ethical review of clinical animal research in the United States of America and propose expanded functions for veterinary clinical studies committees as a solution.
A Modified Liu and Storey Conjugate Gradient Method for Large Scale Unconstrained Optimization Problems
Authors: Salleh Zabidin , Alhamzi Ghaliah , Masmali Ibitsam , Alhawarat Ahmad
Published: July 2021

The conjugate gradient method is one of the most popular methods to solve large-scale unconstrained optimization problems since it does not require the second derivative, such as Newton’s method or approximations. Moreover, the conjugate gradient method can be applied in many fields such as neural networks, image restoration, etc. Many complicated methods are proposed to solve these optimization functions in two or three terms. In this paper, we propose a simple, easy, efficient, and robust conjugate gradient method. The new method is constructed based on the Liu and Storey method to overcome the convergence problem and descent property. The new modified method satisfies the convergence properties and the sufficient descent condition under some assumptions. The numerical results show that the new method outperforms famous CG methods such as CG-Descent 5.3, Liu and Storey, and Dai and Liao. The numerical results include the number of iterations and CPU time.
Passive Control of Low-Frequency Instability in Hybrid Rocket Combustion
Authors: Hyun Wonjeong , Kim Jina , Chae Heesang , Lee Changjin
Published: July 2021

The occurrence of low-frequency instability (LFI) appears to be related to multiple interactions among many complex physical processes, such as vortex shedding, boundary-layer oscillation, and additional combustion in the post-combustion chamber. In this study, two combustion tests were conducted to suppress LFI and to examine which physical processes its occurrence was most sensitive. In the first test, two fuel inserts were used to modify the formation of a boundary layer, vortex shedding at the end of the fuel, and vortex impingement. In the second test, the fuel insert located at the front end was replaced with swirl injection. The first test was aimed at controlling and suppressing the initiation of LFI using fuel inserts, through which a small step appeared gradually due to differences in the regression rates of the two materials, i.e., polymethyl methacrylate and high-density polyethylene. The test results confirmed that (i) there are physical connections among several processes, such as the thermoacoustic coupling between p′and q′ and the oscillations of the upstream boundary flow, and (ii) LFI suppression is possible by disrupting or eliminating the connections among these physical processes. The second test was also aimed to control LFI while minimizing the deviation in combustion performance using proper swirl injection along with a fuel insert. Even when replaced by swirl injection, LFI suppression was still possible and showed reasonable combustion performance without causing too much deviation from the baseline in terms of the oxygen-to-fuel ratio and the fuel regression rate.
Benefits and Trade-Offs of Tillage Management in China: A Meta-Analysis
Authors: Wang Yingcheng , Ying Hao , Yin Yulong , Wang Hongye , Cui Zhenling
Published: July 2021

In China, deep tillage (DT; to >20 cm soil depth) has increased crop yields by improving soil properties, while no-tillage (NT) has been recommended to reduce the labor and machinery costs. Local farmers are willing to adopted rotary tillage (RT; harrowing to 10–15 cm depth) for easy management. However, the effects of these tillage management methods on agronomic productivity, greenhouse gas (GHG) emissions, soil organic carbon (SOC) sequestration, and economic return have not been quantified systematically, and their effectiveness remains in question. Here, we present a meta-analysis of the effects of these methods using 665 paired measurements from 144 peer-reviewed studies. The results indicated that DT significantly increased crop yields by 7.5% relative to RT, and even greater increases were observed in regions with low temperatures and with a wheat cropping system. In contrast, NT resulted in a yield reduction of 3.7% relative to RT, however, controlling for the appropriate temperature and long extension duration (>15 yr) could reduce yield losses and even increase the yield. Both DT and NT significantly enhanced SOC sequestration relative to RT. Adoption of DT would lead to both higher total GHG emissions (N2O and CH4) and increased energy costs, while NT reduced GHG emissions. DT management exhibited a positive net profit for all cropping systems; NT decreased the net profit for rice and wheat but increased the profit for maize. Our study highlighted the agronomic, environmental, and economic benefits and trade-offs for the different tillage methods and should enable investors and policymakers to ensure the best tillage management decisions are made depending on the location-specific conditions.
Molecular Evaluation of Traditional Chicken Farm-Associated Bioaerosols for Methicillin-Resistant Staphylococcus aureus Shedding
Authors: Tao Chi-Wei , Chen Jung-Sheng , Hsu Bing-Mu , Koner Suprokash , Hung Tung-Che , Wu Han-Ming , Rathod Jagat
Published: July 2021

The outbreak of airborne pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA) through bioaerosol, and their molecular characterization around domestic poultry farming areas, was not completely understood. This imposes risk of a MRSA-associated health threat for the relevant livestock food production units. To address this issue, the present study investigated the role of bioaerosol in transmitting MRSA strains in poultry house settings by combining molecular typing, phylogenetic classification, antibiotic susceptibility, and virulence gene distribution patterns. The present study highlights that all 18 bioaerosol and stool samples collected were MRSA positive, with a unique set of virulence factors. Out of 57 isolated MRSA isolates, 68.4% and 19.3% consisted of SCCmec I and IV elements, respectively, which are commonly linked with hospital-acquired and livestock-associated MRSA strains. It is worth noting that the exfoliative toxin eta and etb genes were carried by 100% and 70.2% of all isolates, respectively. Only 17.5% of strains showed the presence of enterotoxin entC. These MRSA isolates were resistant to chloramphenicol (C), ciprofloxacin (CIP), clindamycin (DA), erythromycin (E), and tetracycline (T), signifying their multi-drug resistance traits. A cluster of phylogenetic analysis described that 80.7% and 15.8% of total isolates belonged to Staphylococcus aureus protein A (spa) type t002 and t548. Whereas 3.5% were reflected as a new spa type. Additionally, as per the chi-squared test score value, these two spa types (t002 and t548) have a distribution correlation with HA-MRSA and LA-MRSA in all the samples (p < 0.005, chi-squared test; degree of freedom = 1). Ultimately, this study highlights the prevalence of MRSA colonization in the conventional poultry farm environment, showing the risk of bioaerosol transmission, which needs epidemiological attention and prevention strategies.
Scavenging Properties of Plant-Derived Natural Biomolecule Para-Coumaric Acid in the Prevention of Oxidative Stress-Induced Diseases
Authors: Roychoudhury Shubhadeep , Sinha Barnali , Choudhury Birupakshya Paul , Jha Niraj Kumar , Palit Partha , Kundu Surekha , Mandal Subhash C. , Kolesarova Adriana , Yousef Mokhtar Ibrahim , Ruokolainen Janne , Slama Petr , Kesari Kavindra Kumar
Published: July 2021

Para-coumaric acid (p-CA) is a plant derived secondary metabolite belonging to the phenolic compounds. It is widely distributed in the plant kingdom and found mainly in fruits, vegetables, and cereals. Various in vivo and in vitro studies have revealed its scavenging and antioxidative properties in the reduction of oxidative stress and inflammatory reactions. This evidence-based review focuses on the protective role of p-CA including its therapeutic potential. p-CA and its conjugates possesses various bioactivities such as antioxidant, anti-inflammatory, anti-cancer, anti-diabetic, and anti-melanogenic properties. Due to its potent free radical scavenging activity, it can mitigate the ill effects of various diseases including arthritis, neurological disorders, and cardio-vascular diseases. Recent studies have revealed that p-CA can ameliorate the harmful effects associated with oxidative stress in the reproductive system, also by inhibiting enzymes linked with erectile function.
Changes in Crystal Phase, Morphology, and Flexural Strength of As-Sintered Translucent Monolithic Zirconia Ceramic Modified by Femtosecond Laser
Authors: Liang Shanshan , Ye Hongqiang , Yuan Fusong
Published: July 2021

Conventional bonding technology suitable for silica-based ceramics is not applicable to zirconia, due to its polycrystalline phase composition, chemical stability, and acid corrosion resistance. The development of an effective treatment to improve its surface roughness and mechanical properties remains an unresolved problem. Therefore, to solve this problem, this in vitro study evaluated the changes in surface morphology and flexural strength of translucent monolithic zirconia surfaces treated with femtosecond laser technology. As-sintered translucent zirconia specimens were subjected to airborne particle abrasion and femtosecond laser treatments, while control group specimens received no treatment. After treatment, the roughness and morphology of the treated zirconia surfaces were examined. The flexural strength and X-ray diffraction of the treated specimens were measured and analyzed. Statistical inferential analysis included one-way analysis of variance at a set significance level of 5%. The surface roughness after femtosecond laser treatment was significantly improved when compared with the control group and the group that received the airborne particle abrasion treatment (p < 0.05). In comparison with the airborne particle abrasion group, the flexural strength of the group that received the femtosecond laser treatment was significantly improved (p < 0.05). The femtosecond laser approach using appropriate parameters enhanced the roughness of the zirconia without reducing its flexural strength; therefore, this approach offers potential for the treatment of zirconia surfaces.
Coded Control of a Sectional Electroelastic Engine for Nanomechatronics Systems
Authors: Afonin Sergey
Published: July 2021

This work determines the coded control of a sectional electroelastic engine at the elastic–inertial load for nanomechatronics systems. The expressions of the mechanical and adjustment characteristics of a sectional electroelastic engine are obtained using the equations of the electroelasticity and the mechanical load. A sectional electroelastic engine is applied for coded control of nanodisplacement as a digital-to-analog converter. The transfer function and the transient characteristics of a sectional electroelastic engine at elastic–inertial load are received for nanomechatronics systems.
Geometrical Assessment of Sunlit and Shaded Area of Urban Trees Based on Aligned Orthographic Views
Authors: Gangwisch Marcel , Fröhlich Dominik , Christen Andreas , Matzarakis Andreas
Published: July 2021

To quantify the ecosystem services of trees in urban environments, it is necessary to assess received direct solar radiation of each tree. While the Sky View Factor (SVF) is suitable for assessing the total incoming short- and longwave radiation fluxes, its information is limited to specific points in space. For a spatial analysis, it is necessary to sample the area for SVF. A new geometrical method, Area View Factor (AVF), for the calculation of sunlit areas is proposed. AVF is the ratio of the unhidden, projected surface of an object to the whole projected surface of an object in a complex environment. Hereby, a virtual, orthographic camera is oriented in accordance to the sun’s position in the 3D model domain. The method is implemented in the microscale model SkyHelios, utilizing efficient rendering techniques to assess AVF of all urban trees in parallel. The method was applied to Rieselfeld in Freiburg, Germany. The assessed sunlit area is compared to the SVF at the top of each tree and solar altitude angle, revealing a strong relationship between sunlit areas to solar altitude angles. This study shows that AVF is an efficient methodology to assess received direct radiation of urban trees. Based on AVF, it is possible to identify urban areas with shaded and sunlit trees, but it can also be applied to other objects in complex environments. Therefore, AVF is applicable for urban architecture or energetic research questions.
The Kinematics of Social Action: Visual Signals Provide Cues for What Interlocutors Do in Conversation
Authors: Trujillo James P. , Holler Judith
Published: July 2021

During natural conversation, people must quickly understand the meaning of what the other speaker is saying. This concerns not just the semantic content of an utterance, but also the social action (i.e., what the utterance is doing—requesting information, offering, evaluating, checking mutual understanding, etc.) that the utterance is performing. The multimodal nature of human language raises the question of whether visual signals may contribute to the rapid processing of such social actions. However, while previous research has shown that how we move reveals the intentions underlying instrumental actions, we do not know whether the intentions underlying fine-grained social actions in conversation are also revealed in our bodily movements. Using a corpus of dyadic conversations combined with manual annotation and motion tracking, we analyzed the kinematics of the torso, head, and hands during the asking of questions. Manual annotation categorized these questions into six more fine-grained social action types (i.e., request for information, other-initiated repair, understanding check, stance or sentiment, self-directed, active participation). We demonstrate, for the first time, that the kinematics of the torso, head and hands differ between some of these different social action categories based on a 900 ms time window that captures movements starting slightly prior to or within 600 ms after utterance onset. These results provide novel insights into the extent to which our intentions shape the way that we move, and provide new avenues for understanding how this phenomenon may facilitate the fast communication of meaning in conversational interaction, social action, and conversation.
Cell-Main Spectra Profile Screening Technique in Simulation of Circulating Tumour Cells Using MALDI-TOF Mass Spectrometry
Authors: Chiangjong Wararat , Bhakdi Sebastian Chakrit , Woramongkolchai Noppawan , Vanichapol Thitinee , Pongsakul Nutkridta , Hongeng Suradej , Chutipongtanate Somchai
Published: July 2021

Circulating atypical cells (CAC) are released from a primary tumour site into peripheral blood and are indicators of cancer metastasis. CAC occur at very low frequency in circulating blood, and their detection remains challenging. Moreover, white blood cells (WBC) are the major contaminant in enriched CAC samples. Here, we developed matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) as a novel CAC characterization platform. Main spectra profiles (MSP) of normal and cancer cells were generated by MALDI-TOF MS, and a cell-main spectra database was then compiled and analysed using the MALDI Biotyper software. Logarithmic scores accurately predicted distinct cell types. The feasibility of this workflow was then validated using simulated samples, which were prepared by 5000 WBC of three healthy individuals spiked with varying numbers (3, 6, 12, 25, 50, and 100) of lung, colon, or prostate cancer cells. MALDI-TOF MS was able to detect cancer cells down to six cells over the background noise of 5000 WBC with significantly higher predictive scores as compared to WBC alone. Further development of cell-MSP database to cover all cancer types sourced from cell lines and patient tumours may enable the use of MALDI-TOF MS as a cancer-screening platform in clinical settings in the future.
Microbial Associations with Pancreatic Cancer: A New Frontier in Biomarkers
Authors: Stasiewicz Mark , Kwaśniewski Marek , Karpiński Tomasz M.
Published: July 2021

Pancreatic cancer (PC) remains a global health concern with high mortality and is expected to increase as a proportion of overall cancer cases in the coming years. Most patients are diagnosed at a late stage of disease progression, which contributes to the extremely low 5-year survival rates. Presently, screening for PC remains costly and time consuming, precluding the use of widespread testing. Biomarkers have been explored as an option by which to ameliorate this situation. The authors conducted a search of available literature on PubMed to present the current state of understanding as it pertains to the use of microbial biomarkers and their associations with PC. Carriage of certain bacteria in the oral cavity (e.g., Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Streptococcus sp.), gut (e.g., Helicobacter pylori, Synergistetes, Proteobacteria), and pancreas (e.g., Fusobacterium sp., Enterobacteriaceae, Pseudomonadaceae) has been associated with an increased risk of developing PC. Additionally, the fungal genus Malassezia has likewise been associated with PC development. This review further outlines potential oncogenic mechanisms involved in the microbial-associated development of PC.
Extracellular Vesicles in Advanced Prostate Cancer: Tools to Predict and Thwart Therapeutic Resistance
Authors: Saldana Carolina , Majidipur Amene , Beaumont Emma , Huet Eric , de la Taille Alexandre , Vacherot Francis , Firlej Virginie , Destouches Damien
Published: July 2021

Prostate cancer (PCa) is the second most frequent cancer and the fifth leading cause of cancer death among men worldwide. At first, advanced PCa is treated by androgen deprivation therapy with a good initial response. Nevertheless, recurrences occur, leading to Castrate-Resistance Prostate Cancer (CRPC). During the last decade, new therapies based on inhibition of the androgen receptor pathway or taxane chemotherapies have been used to treat CRPC patients leading to an increase in overall survival, but the occurrence of resistances limits their benefits. Numerous studies have demonstrated the implication of extracellular vesicles (EVs) in different cancer cellular mechanisms. Thus, the possibility to isolate and explore EVs produced by tumor cells in plasma/sera represents an important opportunity for the deciphering of those mechanisms and the discovery of biomarkers. Herein, we summarized the role of EVs in therapeutic resistance of advanced prostate cancer and their use to find biomarkers able to predict these resistances.
Deep Learning Segmentation of Triple-Negative Breast Cancer (TNBC) Patient Derived Tumor Xenograft (PDX) and Sensitivity of Radiomic Pipeline to Tumor Probability Boundary
Authors: Dutta Kaushik , Roy Sudipta , Whitehead Timothy Daniel , Luo Jingqin , Jha Abhinav Kumar , Li Shunqiang , Quirk James Dennis , Shoghi Kooresh Isaac
Published: July 2021

Preclinical magnetic resonance imaging (MRI) is a critical component in a co-clinical research pipeline. Importantly, segmentation of tumors in MRI is a necessary step in tumor phenotyping and assessment of response to therapy. However, manual segmentation is time-intensive and suffers from inter- and intra- observer variability and lack of reproducibility. This study aimed to develop an automated pipeline for accurate localization and delineation of TNBC PDX tumors from preclinical T1w and T2w MR images using a deep learning (DL) algorithm and to assess the sensitivity of radiomic features to tumor boundaries. We tested five network architectures including U-Net, dense U-Net, Res-Net, recurrent residual UNet (R2UNet), and dense R2U-Net (D-R2UNet), which were compared against manual delineation by experts. To mitigate bias among multiple experts, the simultaneous truth and performance level estimation (STAPLE) algorithm was applied to create consensus maps. Performance metrics (F1-Score, recall, precision, and AUC) were used to assess the performance of the networks. Multi-contrast D-R2UNet performed best with F1-score = 0.948; however, all networks scored within 1–3% of each other. Radiomic features extracted from D-R2UNet were highly corelated to STAPLE-derived features with 67.13% of T1w and 53.15% of T2w exhibiting correlation ρ ≥ 0.9 (p ≤ 0.05). D-R2UNet-extracted features exhibited better reproducibility relative to STAPLE with 86.71% of T1w and 69.93% of T2w features found to be highly reproducible (CCC ≥ 0.9, p ≤ 0.05). Finally, 39.16% T1w and 13.9% T2w features were identified as insensitive to tumor boundary perturbations (Spearman correlation (−0.4 ≤ ρ ≤ 0.4). We developed a highly reproducible DL algorithm to circumvent manual segmentation of T1w and T2w MR images and identified sensitivity of radiomic features to tumor boundaries.
Human Wnt/β-Catenin Regulates Alloimmune Signaling during Allogeneic Transplantation
Authors: Mammadli Mahinbanu , Harris Rebecca , Mahmudlu Sara , Verma Anjali , May Adriana , Dhawan Rohan , Waickman Adam T. , Sen Jyoti Misra , August Avery , Karimi Mobin
Published: July 2021

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the most widely applied forms of adoptive immunotherapy for the treatment of hematological malignancies. Detrimental graft-versus-host disease (GVHD), but also beneficial graft-versus-leukemia (GVL) effects occurring after allo-HSCT are largely mediated by alloantigen-reactive donor T cells in the graft. Separating GVHD from GVL effects is a formidable challenge, and a greater understanding of donor T cell biology is required to accomplish the uncoupling of GVHD from GVL. Here, we evaluated the role of β-catenin in this process. Using a unique mouse model of transgenic overexpression of human β-catenin (Cat-Tg) in an allo-HSCT model, we show here that T cells from Cat-Tg mice did not cause GVHD, and surprisingly, Cat-Tg T cells maintained the GVL effect. Donor T cells from Cat-Tg mice exhibited significantly lower inflammatory cytokine production and reduced donor T cell proliferation, while upregulating cytotoxic mediators that resulted in enhanced cytotoxicity. RNA sequencing revealed changes in the expression of 1169 genes for CD4, and 1006 genes for CD8+ T cells involved in essential aspects of immune response and GVHD pathophysiology. Altogether, our data suggest that β-catenin is a druggable target for developing therapeutic strategies to reduce GVHD while preserving the beneficial GVL effects following allo-HSCT treatment.