bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase I Clinical Trial of an Autologous Dendritic Cell Vaccine Against HER2 Shows Safety and Preliminary Clinical Efficacy
Authors: Maeng Hoyoung M. , Moore Brittni N. , Bagheri Hadi , Steinberg Seth M. , Inglefield Jon , Dunham Kim , Wei Wei-Zen , Morris John C. , Terabe Masaki , England Lee C. , Roberson Brenda , Rosing Douglas , Sachdev Vandana , Pack Svetlana D. , Miettinen Markku M. , Barr Frederic G. , Weiner Louis M. , Panch Sandhya , Stroncek David F. , Wood Lauren V. , Berzofsky Jay A.
Published: December 2021

Background

Despite recent advances, there is an urgent need for agents targeting HER2-expressing cancers other than breast cancer. We report a phase I study (NCT01730118) of a dendritic cell (DC) vaccine targeting HER2 in patients with metastatic cancer or bladder cancer at high risk of relapse.

Patients and Methods

Part 1 of the study enrolled patients with HER2-expressing metastatic cancer that had progressed after at least standard treatment and patients who underwent definitive treatment for invasive bladder cancer with no evidence of disease at the time of enrollment. Part 2 enrolled patients with HER2-expressing metastatic cancer who had progressed after anti-HER2 therapy. The DC vaccines were prepared from autologous monocytes and transduced with an adenoviral vector expressing the extracellular and transmembrane domains of HER2 (AdHER2). A total of five doses were planned, and adverse events were recorded in patients who received at least one dose. Objective response was evaluated by unidimensional immune-related response criteria every 8 weeks in patients who received at least two doses. Humoral and cellular immunogenicity were assessed in patients who received more than three doses.

Results

A total of 33 patients were enrolled at four dose levels (5 × 106, 10 × 106, 20 × 106, and 40 × 106DCs). Median follow-up duration was 36 weeks (4–124); 10 patients completed five doses. The main reason for going off-study was disease progression. The main adverse events attributable to the vaccine were injection-site reactions. No cardiac toxicity was noted. Seven of 21 evaluable patients (33.3%) demonstrated clinical benefit (1 complete response, 1 partial response, and 5 stable disease). After ≥3 doses, an antibody response was detected in 3 of 13 patients (23.1%), including patients with complete and partial responses. Lymphocytes from 10 of 11 patients (90.9%) showed induction of anti-HER2 responses measured by the production of at least one of interferon-gamma, granzyme B, or tumor necrosis factor-alpha, and there were multifunctional responses in 8 of 11 patients (72.7%).

Conclusions

The AdHER2 DC vaccine showed evidence of immunogenicity and preliminary clinical benefit in patients with HER2-expressing cancers, along with an excellent safety profile. It shows promise for further clinical applications, especially in combination regimens.
Research Advances in the Role of the Poly ADP Ribose Polymerase Family in Cancer
Authors: Sha Huanhuan , Gan Yujie , Zou Renrui , Wu Jianzhong , Feng Jifeng
Published: December 2021

Poly ADP ribose polymerases (PARPs) catalyze the modification of acceptor proteins, DNA, or RNA with ADP-ribose, which plays an important role in maintaining genomic stability and regulating signaling pathways. The rapid development of PARP1/2 inhibitors for the treatment of ovarian and breast cancers has advanced research on other PARP family members for the treatment of cancer. This paper reviews the role of PARP family members (except PARP1/2 and tankyrases) in cancer and the underlying regulatory mechanisms, which will establish a molecular basis for the clinical application of PARPs in the future.
Case Report: Exceptional Response to Nivolumab Plus Ipilimumab in a Young Woman With TFE3-SFPQ Fusion Translocation-Associated Renal Cell Carcinoma
Authors: Martini Dylan J. , Jansen Caroline S. , Harik Lara R. , Evans Sean T. , Olsen T. Anders , Master Viraj A. , Kissick Haydn T. , Bilen Mehmet Asim
Published: December 2021

Translocation-associated renal cell carcinoma (tRCC) is a rare, aggressive malignancy that primarily affects children and young adults. There is no clear consensus on the most effective treatment for tRCC and there are no biomarkers of response to treatments in these patients. We present a case of a 23 year-old female with metastatic tRCC to the lungs who was started on treatment with nivolumab and ipilimumab. She had a complete radiographic response to treatment and has been progression-free for over 18 months. Immunofluorescence imaging performed on the baseline primary tumor sample showed significant intratumoral immune infiltration. Importantly, these cells are present in niches characterized by TCF1+ CD8+ T cells. Histopathologic investigation showed the presence of lymphocytes in the fibrovascular septae and foci of lymphovascular invasion. Furthermore, lymphovascular invasion and intratumor niches with TCF1+ CD8+ T cells may predict a favorable response to treatment with nivolumab and ipilimumab. These findings have significant clinical relevance given that immune checkpoint inhibitors are approved for several malignancies and predictive biomarkers for response to treatment are lacking. Importantly, the identification of these TCF1+ CD8+ T cells may guide treatment for patients with tRCC, which is a rare malignancy without a consensus first-line treatment option.
Pediatric Endoscopy During COVID-19 Times
Authors: Shaoul Ron , Day Andrew S.
Published: December 2021

The global COVID-19 pandemic has led to healthcare resources being diverted or stretched, especially during periods of lock-down in affected countries. Disruptions to normal services have resulted in reduced or delayed provision of endoscopy in many countries, with consequent impacts on diagnosis or management of digestive diseases and upon endoscopy training. This review article aims to highlight key aspects of the impact of the pandemic upon endoscopy services, with a focus upon endoscopy in children.
Digital Image Analysis Tools Developed by the Indiana O’Brien Center
Authors: Dunn Kenneth W.
Published: December 2021

The scale and complexity of images collected in biological microscopy have grown enormously over the past 30 years. The development and commercialization of multiphoton microscopy has promoted a renaissance of intravital microscopy, providing a window into cell biology in vivo. New methods of optical sectioning and tissue clearing now enable biologists to characterize entire organs at subcellular resolution. New methods of multiplexed imaging support simultaneous localization of forty or more probes at a time. Exploiting these exciting new techniques has increasingly required biomedical researchers to master procedures of image analysis that were once the specialized province of imaging experts. A primary goal of the Indiana O’Brien Center has been to develop robust and accessible image analysis tools for biomedical researchers. Here we describe biomedical image analysis software developed by the Indiana O’Brien Center over the past 25 years.
MPOWER: The Impact of a Purpose Program on Adolescents’ Intrinsic and Extrinsic Motivations
Authors: Sepulveda Jonathan A. , Lincoln Brenna , Liang Belle , Klein Timothy , White Allison E. , Hill Nancy , Perella John
Published: December 2021

Purpose has been defined as an active engagement toward goals that are meaningful to the self (i.e., personal meaningfulness) and contribute to the world beyond the self (BTS). These BTS contributions may reflect the intention to meet a wide range of needs from family financial needs to more macro-level concerns, including social injustices. This study investigates the efficacy of a school-based program called MPOWER expressly designed by the authors to cultivate the BTS aspect of purpose. Previous research suggests that the BTS aspect of purpose has beneficial effects on school engagement, goal-setting abilities and orientations, and ultimately school performance. Ninety-four students participated in this study that utilized a randomized, pre-test-post-test between-subjects design to evaluate MPOWER (52 in MPOWER and 42 in the control group). The ANCOVA results indicated a significant increase in the BTS aspect of purpose among program participants, compared to controls. Moreover, participants had higher post-test levels of general self-efficacy and grade point averages, and decreased performance-approach (e.g., playing to be the best, comparing self to others) and performance-avoidance (e.g., avoiding risks of failure, fear of social consequences) goal orientations. Findings can be used to design programs that aim to cultivate students’ intentions to contribute to the world beyond themselves, as well as associated personal benefits (i.e., goal orientations, self-efficacy, academic performance).
Ingroup Bias in Healthcare Contexts: Israeli-Jewish Perceptions of Arab and Jewish Doctors
Authors: Graham Elliot , Halabi Samer , Nadler Arie
Published: December 2021

The influence of group membership on perceptions of outgroup members has been extensively studied in various contexts. This research has indicated a strong tendency for ingroup bias – preferring the ingroup over the outgroup. We seek to further expand on the growing literature regarding the effects of group membership within healthcare contexts. Focusing on the Arab-Jewish context in Israel, the present study explored the influence of group membership on Israeli-Jewish participants’ evaluations when exposed to potential malpractice. Specifically, participants (n = 165) read a description of an Israeli-Jewish or Israeli-Arab physician who was either culpable or non-culpable of malpractice. Consistent with our predictions, findings generally indicated more negative evaluations of the Israeli-Arab physician, regardless of objective culpability. We conclude by discussing the study’s limitations and implications.
Assessment of Counseling Self-Efficacy: Validation of the German Counselor Activity Self-Efficacy Scales-Revised
Authors: Hahn Daniela , Weck Florian , Witthöft Michael , Kühne Franziska
Published: December 2021

Background: Many authors regard counseling self-efficacy (CSE) as important in therapist development and training. The purpose of this study was to examine the factor structure, reliability, and validity of the German version of the Counselor Activity Self-Efficacy Scales-Revised (CASES-R).

Method: The sample consisted of 670 German psychotherapy trainees, who completed an online survey. We examined the factor structure by applying exploratory and confirmatory factor analysis to the instrument as a whole.

Results: A bifactor-exploratory structural equation modeling model with one general and five specific factors provided the best fit to the data. Omega hierarchical coefficients indicated optimal reliability for the general factor, acceptable reliability for the Action Skills-Revised (AS-R) factor, and insufficient estimates for the remaining factors. The CASES-R scales yielded significant correlations with related measures, but also with therapeutic orientations.

Conclusion: We found support for the reliability and validity of the German CASES-R. However, the subdomains (except AS-R) should be interpreted with caution, and we do not recommend the CASES-R for comparisons between psychotherapeutic orientations.
Regenerative Green Infrastructure Governance in Weak, Rebounding, and Wealthy Land Markets
Authors: Foo Katherine
Published: December 2021

Too often scholars valorize green infrastructure without critically examining the dynamic and multi-faceted ways that greening impacts urban environments. Cities are complex, evolving forces of their own, which grow and shrink according to time and place. Governance strategies in different economic conditions powerfully shape the impacts of specific green infrastructure installations. They determine the value, quality, quantity, and spatial arrangement of green infrastructure. However, most scholarship focuses on the psychological, social, economic, and environmental benefits of urban greening. Green infrastructure is overwhelmingly studied as apart from historical urban governance trajectories, and it largely fails to consider the role of greening within the process of urban regeneration. This disconnect constitutes a significant gap that constrains understanding of green infrastructure for regenerative cities, and it limits our ability to strategically deploy it in beneficial rather than harmful or irrelevant ways. In this article, I argue that green infrastructure lays fundamentally different roles in poor and wealthy parts of cities, and that these roles change as the overall rank and status of the cities change over time. These changing meanings cause city governments to treat green infrastructure as fundamentally different targets of management. These conclusions are based on an ethnography of the public policy processes surrounding urban greening in three cities with different land markets. In the strong land market, the emphasis is placed firmly on revenue-generating projects, and the major players are private firms in conjunction with city departments. Greening is conceived as a byproduct of large-scale development projects, and rarely apart from them. In the weak land market city, in contrast, the environmental and civic organizations play major roles, and they conceive of green infrastructure apart from development projects. Weak land markets seem to create the possibility for increased political participation of environmental actors and for the installation of green infrastructure for the primary purpose of community health and well-being. However, the increased strength of environmental civic coalitions appears negatively correlated with the city's economic capacity to fund greening projects without support from the business community. These dynamics suggest a counter-cyclical relationship between the political will for urban greening and the investment capacity to pay for it. The analysis of green infrastructure in different land markets demonstrates that green infrastructure is deeply embedded in the historical and geographical legacies of cities.
What Studying the Songs of a Distant Primate Relative Can Teach Us About Ourselves
Authors: Clink Dena Jane
Published: December 2021

Tarsiers are nocturnal animals. They have eyes that are heavier than their brains. They eat only insects and other living things. Tarsiers are primates, just like humans. And some species of tarsiers sing! Tarsier songs and human language are different in many ways. But if we study the similarities, it may help us better understand human language. In our study, we recorded singing tarsiers on the Indonesian island of Sulawesi. With the help of computers, we found that we could tell individual tarsiers apart based on their songs. Being able to recognize who is singing from far away may be an important function of tarsier songs. We also found that if a female speeds up her song, then the male speeds up his song, too. The ability to modify vocal output based on what others are doing is a universal in human language. Our results show that tarsiers (like humans) can change their vocalizations based on what their partner is doing. The fact that tarsiers and humans are both able to do this indicates that their common ancestor probably had this ability. Our results add support to the idea that flexibility in vocal interactions evolved long before the appearance of modern humans.
Concept Creep and Psychiatrization
Authors: Haslam Nick , Tse Jesse S. Y. , De Deyne Simon
Published: December 2021

Some aspects of psychiatrization can be understood as forms of concept creep, the progressive expansion of concepts of harm. This article compares the two concepts and explores how concept creep sheds light on psychiatrization. We argue that although psychiatrization is in some respects a broader concept than concept creep, addressing institutional and societal dimensions of the expanding reach of psychiatry in addition to conceptual change, concept creep is broader in other respects, viewing the expansion of psychiatric concepts as examples of the broadening of a more extensive range of harm-related concepts. A concept creep perspective on psychiatrization clarifies the different forms of expansion it involves, the centrality of harm to it, its benefits as well as its costs, its variations across individuals and groups, and the drivers of psychiatrization in the general public and in fields beyond psychiatry.
Engaging Minority Girls in Organized Youth Sport in Norway: A Case Study of a Project That Worked
Authors: Gjesdal Siv , Hedenborg Susanna
Published: December 2021

Sport participation is considered a positive pastime endower that can offer a range of positive outcomes for children and youths. It has also increasingly been recognized as a potentially important context for fostering social inclusion for minority youths. Yet across Europe, minority girls are participating in sport to a lesser degree than their majority counterparts. Using self-determination theory (SDT) and the social ecological model as the framework, this study explored the reasons why a particular project aimed at recruiting minority girls to organized team sport succeeded in doing just that. A case study design was adopted to provide an in-depth analysis of how this project satisfied the basic psychological needs of minority girls. Nine girls, four parents, two coaches, and two project team members were interviewed about the project and sport participation in general. Data were analyzed using thematic analysis. Two main themes were identified, a sense of being facilitated and inclusion in the sport environment. The former emphasized the importance of aligning the participation with the girls' cultural norms and values, particularly in the beginning. It also included practical issues such as finances, reminding us that participation in sport is not just a motivational issue. The latter focused on the importance of including the girls in the general sports program, regardless of their athletic abilities at the onset of their participation and creating a mastery environment. Moreover, by removing remediable differences between the minority and majority girls, such as having the right equipment, seemed important to fostering a sense of belonging in the sports club. Additionally, establishing meaningful relationships with coaches and majority counterparts seemed to be a major motivating factor.
Rhinoceros Serum microRNAs: Identification, Characterization, and Evaluation of Potential Iron Overload Biomarkers
Authors: Wojtusik Jessye , Curry Erin , Roth Terri L.
Published: December 2021

Iron overload disorder (IOD) in critically endangered Sumatran (Dicerorhinus sumatrensis) and black (Diceros bicornis) rhinoceros is an over-accumulation of iron in organs which may exacerbate other diseases and indicate metabolic disturbances. IOD in rhinos is not well understood and diagnostics and therapeutics are limited in effectiveness. MicroRNAs (miRNAs) are small non-coding RNAs capable of altering protein synthesis. miRNA expression responds to physiological states and could serve as the basis for development of diagnostics and therapeutics. This study aimed to identify miRNAs differentially expressed among healthy rhinos and those afflicted with IOD or other diseases (“unhealthy”), and assess expression of select miRNAs to evaluate their potential as biomarkers of IOD. miRNAs in serum of black (n = 11 samples; five individuals) and Sumatran (n = 7 samples; four individuals) rhinos, representing individuals categorized as healthy (n = 9), unhealthy (n = 5), and afflicted by IOD (n = 3) were sequenced. In total, 715 miRNAs were identified, of which 160 were novel, 131 were specific to black rhinos, and 108 were specific to Sumatran rhinos. Additionally, 95 miRNAs were specific to healthy individuals, 31 specific to unhealthy, and 63 were specific to IOD individuals. Among healthy, unhealthy, and IOD states, 21 miRNAs were differentially expressed (P ≤ 0.01). Five known miRNAs (let-7g, miR-16b, miR-30e, miR-143, and miR-146a) were selected for further assessment via RT-qPCR in serum from black (n = 61 samples; seven individuals) and Sumatran (n = 38 samples; five individuals) rhinos. let-7g, miR-30e, and miR-143 all showed significant increased expression (P ≤ 0.05) during IOD (between 1 and 2 years prior to death) and late IOD (within 1 year of death) compared to healthy and unhealthy individuals. miR-16b expression increased (P ≤ 0.05) in late IOD, but was not different among IOD, healthy, and unhealthy states (P > 0.05). Expression of miR-146a increased in IOD and late IOD as compared to unhealthy samples (P ≤ 0.05) but was not different from the healthy state (P > 0.05). Selected serum miRNAs of black and Sumatran rhinos, in particular let-7g, miR-30e, and miR-143, could therefore provide a tool for advancing rhino IOD diagnostics that should be further investigated.
Assessing the Impact of a Virtual Shelter Medicine Rotation on Veterinary Students' Knowledge, Skills, and Attitudes Regarding Access to Veterinary Care
Authors: Hoffman Christy L. , Spencer Terry G. , Makolinski Kathleen V.
Published: December 2021

Strong bonds commonly form between companion animals and people of all socio-demographic backgrounds, yet many pet owners face numerous barriers to accessing veterinary care for their companion animals. For example, they may have difficulties paying for care; they may lack veterinary practices in their community; and they may experience language barriers that impede their ability to utilize veterinary services. Various strategies exist that can help veterinarians address the diverse needs of pet owners in their communities, but these techniques are not commonly covered in the veterinary school curriculum. This study explored how including in-depth, purposefully curated information about access to veterinary care issues within a required shelter medicine rotation impacted fourth-year veterinary students' knowledge, skills, and attitudes regarding the problems clients commonly face when seeking access to veterinary care. Students participated either in a control group of a virtual, four-week rotation delivered via Zoom meetings and self-study, or in an experimental group that additionally completed an interactive online learning module. The online module heavily featured issues surrounding access to veterinary care. Irrespective of which version of the rotation students enrolled, their opinions grew more favorable from pretest to post-test regarding the role of not-for-profit veterinary clinics in communities, as did their expectations that veterinarians should provide affordable treatment options. Additionally, students in the experimental group demonstrated from pretest to post-test increased awareness of the potential for implicit bias toward pet owners within veterinary practice and showed a reduction in their tendency to be judgmental of veterinary clients. By the end of the study, students in the experimental group also expressed greater confidence in their ability to offer incremental care treatment options to veterinary clients. These findings suggest that providing content that focuses on increasing access to veterinary care enhances students' awareness of the need to offer a variety of treatment and payment options to clients. Findings from this study can inform curriculum design in veterinary schools and continuing education programs for veterinary professionals.
The Advance and Correlation of KRAS Mutation With the Fertility-Preservation Treatment of Endometrial Cancer in the Background of Molecular Classification Application
Authors: Yu KeXuan , Wang Yiqin
Published: December 2021

The annually increasing incidence of endometrial cancer in younger women has created a growing demand for fertility preservation. However, the diverse therapeutic efficacy among patients under the same histological subtype and the same tumor grade suggests the potential interference of the innate molecular characteristics. The molecular classification has now been applied in clinical practice and might help to stratify the endometrial cancer patients and individualize the therapy, but the candidates for the fertility-spared treatment are most likely to be subdivided in the subgroup lacking the specific signature. KRAS mutation has been linked to the malignant transition of the endometrium, while its role in molecular classification and fertility preservation is vague. Here, we mainly review the advance of molecular classification and the role of KRAS in endometrial cancer, as well as their correlation with fertility-preservation treatment.
A Territorial-Driven Approach to Capture the Transformative Momentum of the Social Economy Especially from the Agricultural Cooperatives
Authors: Gallego-Bono Juan Ramón , Tapia-Baranda MariaR
Published: December 2021

In the last few lustrums, the literature has searched for more precise methods to assess the socio-economic importance of the Social and Solidarity Economy (SSE). On that basis, this article offers a new way of assessing the SSE impact, enhancing the understanding of the SSE potential for socio-economic transformation. An evolutionary micro–meso–macro and territorial theoretical framework is developed, utilizing, along with the assistance of a qualitative methodology, studies on the transformation promoted by the SSE on the sugar cane cluster of Veracruz (Mexico). The main results of the article are that the SSE boost beneficiaries, while the protagonists of the transformation cannot be defined a priori, but are rather conformed by transformation vectors promoted by the SSE: their values shared by a wide spectrum of actors, the SSE socio-economic and organizational specificities, and their rooting in the productive system. The fundamental conclusion of the article is the need for a “territorial-driven approach” of the SSE’s impact, compared to the dominant “stakeholder-driven approach”. The main limitations (and suggestions for future studies) are the empirical investigation of a single case, and the need to develop a qualitative and quantitative system of indicators of the transformative drive of SSE.
Management of Soil Constraints to Improve Crop Performance in Water-Limited Environments
Authors: Anderson Geoffrey C. , Barrett-Lennard Edward G.
Published: December 2021

One current challenge for agricultural production in water-limited environments is to develop agronomic management practices that can overcome soil constraints and provide an economic return to the grower in both the short and long-term [...]
Long-Term Effects of Amendment with Olive Mill Wastewater on Soil Chemical Properties, Microbial Community, and Olive Tree Vegetative and Productive Activities
Authors: Regni Luca , Pezzolla Daniela , Ciancaleoni Simona , Marozzi Giorgio , Albertini Emidio , Gigliotti Giovanni , Proietti Primo
Published: December 2021

The long-term effects of the olive mill wastewater (OMWW) spreading on soil chemical properties, microbial community, and olive tree parameters have been far poorly investigated. Therefore, this study aims to evaluate the effect of OMWW application on an olive orchard, and samples were collected at two different depths (0–20 cm and 20–40 cm) and 14 days, one year and two years from the end of the OMWW spreading on soil chemical characteristics and soil microbial structures. Variations of soil chemical parameters (pH, salinity, available P, and water-extractable organic C) were observed particularly at 14 days after spreading at both depths. All these parameters reached similar values to the soil after two years, except for available phosphorus. Firmicutes, Proteobacteria, and Actinobacteria are the most abundant phyla: only Firmicutes were negatively affected by the OMWW spreading after 14 days, suggesting that Gram-positive bacteria were probably negatively influenced by the addition of OMWW. The abundance of bacterial taxa in the soil is restored along time, except for the decrease of Firmicutes. This evidence suggests that the OMWW spreading in the long term does not affect the endemic soil bacterial community of the olive grove, as well as leaf net photosynthesis, the olive tree vegetative activity, yield, and fruits characteristics.
Antimicrobial Resistance in Isolates from Cattle with Bovine Respiratory Disease in Bavaria, Germany
Authors: Melchner Alexander , van de Berg Sarah , Scuda Nelly , Feuerstein Andrea , Hanczaruk Matthias , Schumacher Magdalena , Straubinger Reinhard K. , Marosevic Durdica , Riehm Julia M.
Published: December 2021

Patterns of antimicrobial resistance (AMR) regarding Pasteurella multocida (n = 345), Mannheimia haemolytica (n = 273), Truperella pyogenes (n = 119), and Bibersteinia trehalosi (n = 17) isolated from calves, cattle and dairy cows with putative bovine respiratory disease syndrome were determined. The aim of this study was to investigate temporal trends in AMR and the influence of epidemiological parameters for the geographic origin in Bavaria, Germany, between July 2015 and June 2020. Spectinomycin was the only antimicrobial agent with a significant decrease regarding not susceptible isolates within the study period (P. multocida 88.89% to 67.82%, M. haemolytica 90.24% to 68.00%). Regarding P. multocida, significant increasing rates of not susceptible isolates were found for the antimicrobials tulathromycin (5.56% to 26.44%) and tetracycline (18.52% to 57.47%). The proportions of multidrug-resistant (MDR) P. multocida isolates (n = 48) increased significantly from 3.70% to 22.90%. The proportions of MDR M. haemolytica and P. multocida isolates (n = 62) were significantly higher in fattening farms (14.92%) compared to dairy farms (3.29%) and also significantly higher on farms with more than 300 animals (19.49%) compared to farms with 100 animals or less (6.92%). The data underline the importance of the epidemiological farm characteristics, here farm type and herd size regarding the investigation of AMR.
Potential Applications of Moringa oleifera in Poultry Health and Production as Alternative to Antibiotics: A Review
Authors: Khan Rifat Ullah , Khan Aamir , Naz Shabana , Ullah Qudrat , Laudadio Vito , Tufarelli Vincenzo , Ragni Marco
Published: December 2021

Because of developing bacterial resistance and increased public awareness of health and food safety problems, the use of antibiotics as growth promoters in the chicken industry has been outlawed. This problem has spurred the poultry industry and sector to explore for safe antibiotic alternatives and to focus on developing better long-term feed management solutions in order to improve chicken health and growth. As a result, phytogenics have developed as natural antibiotic alternatives, with a lot of potential in the poultry industry. Moringa oleifera has gotten a lot of attention from researchers in the recent past as a natural product with a lot of health advantages for poultry. Moringa is known for its antimicrobial, antioxidant, anti-inflammatory, and hypocholesterolemic properties, as well as its capacity to activate digestive enzymes in the stomach, owing to the presence of hundreds of essential ingredients. The potential influence of M. oleifera as a natural feed supplement on overall gut health, nutritional digestibility, blood biochemical profile, antioxidant benefits, antibacterial potential, and immunological response is emphasized in this review.
Association of Serum Bilirubin and Functional Variants of Heme Oxygenase 1 and Bilirubin UDP-Glucuronosyl Transferase Genes in Czech Adult Patients with Non-Alcoholic Fatty Liver Disease
Authors: Petrtýl Jaromír , Dvořák Karel , Stříteský Jan , Leníček Martin , Jirásková Alena , Šmíd Václav , Haluzík Martin , Brůha Radan , Vítek Libor
Published: December 2021

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disorder worldwide. The aim of our study was to assess the role of bilirubin, and the heme oxygenase 1 (HMOX1) and bilirubin UDP-glucuronosyl transferase (UGT1A1) promoter gene variants, which are involved in bilirubin homeostasis, in the NAFLD development in adult patients. The study was performed on 84 patients with NAFLD and 103 age/sex-matched controls. Routine biochemistry, inflammatory markers, adipokines, and the fibrosis/steatohepatitis stage were determined in the NAFLD patients. The (GT)n/(TA)n dinucleotide variations in HMOX1/UGT1A1 gene promoters, respectively, were analyzed by fragment analysis. Compared to controls, serum bilirubin concentrations in NAFLD patients tended to be decreased, while the prevalence of phenotypic Gilbert syndrome was significantly low. Genetic variations in HMOX1 and UGT1A1 gene promoters did not differ between NAFLD patients and controls, and no relationship was found in the NAFLD patients between these gene variants and any of the laboratory or histological parameters. In conclusion, metabolism of bilirubin is dysregulated in NAFLD patients, most likely due to increased oxidative stress, since frequencies of the major functional variants in the HMOX1 or UGT1A1 gene promoters did not have any effect on development of NAFLD in adult patients.
Association of Circulating Heme Oxygenase-1, Lipid Profile and Coronary Disease Phenotype in Patients with Chronic Coronary Syndrome
Authors: Caselli Chiara , De Caterina Raffaele , Ragusa Rosetta , Liga Riccardo , Gimelli Alessia , Scholte Arthur J. H. A. , Clerico Aldo , Knuuti Juhani , Neglia Danilo
Published: December 2021

Background. The NF-E2–related factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1) pathway has an emerging role in atherosclerosis. Activated by oxidative stress, it is deemed to exert athero-protective effects. We aimed at evaluating the relationships between plasma HO-1, clinical/molecular profiles and coronary disease patterns in patients with chronic coronary syndromes (CCS). Methods. HO-1 was measured in 526 patients (60 ± 9 years, 318 males) with CCS. Coronary computed tomography angiography (CTA) and stress imaging were used to assess the disease phenotype (coronary atherosclerosis and myocardial ischemia) in a subgroup of 347 patients. Results. In the overall population, HO-1 median value (25–75 percentile) was 5.195 (1.75–8.25) ng/mL. Patients with higher HO-1 were more frequently male, had a higher BMI and lower LVEF%, but otherwise similar risk factors than the other patients. Their bio-humoral profile was characterized by higher markers of endothelial/myocardial dysfunction, but lower levels of cholesterol lipoproteins. Coronary artery disease was characterized by more diffuse atherosclerosis, with mainly non-obstructive and calcified plaques, and a higher prevalence of functional ischemia. Conclusion: In patients with CCS, higher plasma HO-1 levels are associated with lower cholesterol and a more diffuse but mainly non-obstructive coronary atherosclerosis, confirming a potential role for the Nrf2/HO-1 pathway as a protective feedback.
LC-MS/HRMS Analysis, Anti-Cancer, Anti-Enzymatic and Anti-Oxidant Effects of Boerhavia diffusa Extracts: A Potential Raw Material for Functional Applications
Authors: Sinan Kouadio Ibrahime , Akpulat Uğur , Aldahish Afaf A. , Celik Altunoglu Yasemin , Baloğlu Mehmet Cengiz , Zheleva-Dimitrova Dimitrina , Gevrenova Reneta , Lobine Devina , Mahomoodally Mohamad Fawzi , Etienne Ouattara Katinan , Zengin Gokhan , Mahmud Shafi , Capasso Raffaele
Published: December 2021

Boerhavia diffusa is a great tropical plant and is widely used for various traditional purposes. In the present study, we examined the influence of solvents (dichloromethane, ethyl acetate, methanol and infusion (water)) on chemical composition and biological capabilities of B. diffusa. An UHPLC-HRMS method was used to determine the chemical characterization. The biological ability was examined for antioxidant, enzyme inhibitory and anti-cancer effects. To evaluate antioxidant effects, different chemical methods (ABTS, DPPH, CUPRAC, FRAP, metal chelating and phosphomolybdenum) were applied. With regard to enzyme inhibitory properties, cholinesterases, amylase, glucosidase and tyrosinase were used. The MDA-MB-231 breast cancer cell line was chosen to determine anticancer activity. Based on the UHPLC-HRMS analysis, 37 specialized metabolites were dereplicated and identified in the studied extracts. Results revealed the presence of 15 hydroxybenzoic, hydroxycinnamic, acylquinic acids, and their glycosides, one rotenoid, seven flavonoids, 12 fatty acids and two other glycosides. Among the tested extracts, the methanol extract showed a stronger antioxidant ability compared with other extracts. The methanol extract also showed the best inhibitory effects on tyrosinase and glucosidase. In the anti-cancer evaluation, the methanol extract showed stronger anticancer effects compared with water extract. In summary, our observations can contribute to the establishment of B. diffusa as a potential candidate for functional applications in the preparation.
Low Dietary n6/n3 Ratio Attenuates Changes in the NRF 2 Gene Expression, Lipid Peroxidation, and Inflammatory Markers Induced by Fructose Overconsumption in the Rat Abdominal Adipose Tissue
Authors: Roškarić Petra , Šperanda Marcela , Mašek Tomislav , Verbanac Donatella , Starčević Kristina
Published: December 2021

The objective of this study was to examine the benefits of different n6/n3 polyunsaturated fatty acid ratios on the lipid metabolism, insulin resistance, and oxidative stress in the adipose tissue of rats fed a high-fructose diet. Male and female rats were divided into four groups: a control group (CON) (n6/n3 ratio ~7), a high-fructose group (HF) (n6/n3 ratio ~7), an N6-HF group (n6/n3 ratio ~50), and the DHA-HF group (n6/n3 ratio ~1, with the addition of docosahexaenoic (DHA) and eicosapentaenoic (EPA) acid). The CON group received plain water and the HF group received 15% fructose in their drinking water. Fructose induced an increase in the content of serum triglycerides, serum cholesterol, and HOMA-IR index. Among the fatty acids, elevated proportions of C18:1n9 and C16:1n7, as well as an increase in total monounsaturated fatty acid (MUFA), were found in the adipose tissue of the HF group. Fructose treatment also changed oxidative parameters, including a marked increase in the serum malondialdehyde (MDA) content. Meanwhile, DHA supplementation caused a significant decrease in the serum MDA concentration in comparison with the HF group. In addition, DHA/EPA supplementation attenuated oxidative stress by increasing NRF 2 gene expression. Fructose treatment also significantly decreased the adiponectin level, while DHA supplementation ameliorated it. The changes observed in this trial, including the decrease in the content of DHA and EPA, the decreased EPA/ARA ratio, and the increase in the expression of inflammatory genes, are characteristics of the low-grade inflammation caused by fructose treatment. These changes in the rat adipose tissue could be prevented by dietary intervention consisting of DHA supplementation and a low n6/n3 ratio.
Antioxidants into Nopal (Opuntia ficus-indica), Important Inhibitors of Free Radicals’ Formation
Authors: Castañeda-Arriaga Romina , Perez-Gonzalez Adriana , Marino Tiziana , Russo Nino , Galano Annia
Published: December 2021

Nopal (Opuntia ficus indica) belonging to the Cactacea family has many nutritional benefits attributed to a wide variety of phenolic and flavonoid compounds. Coumaric acid (COA), ferulic acid (FLA), protocatechuic acid (PRA), and gallic acid (GAA) are the phenolic acids (PhAs) present in nopal. In this study, the role of these PhAs in copper-induced oxidative stress was investigated using the density functional theory (DFT). The PhAs form 5 thermodynamically favorable complexes with Cu(II), their conditional Gibbs free energies of reaction (ΔG’, at pH = 7.4, in kcal/mol) are from −23 kcal/mol to −18 kcal/mol. All of them are bi-dentate complexes. The complexes of PRA and GAA are capable of inhibiting the Cu(II) reduction by both O2•− and Asc−, their reactions with the chelated metal are endergonic having rate constants about ~10−5–102 M−1 s−1, PhAs can prevent the formation of hydroxyl free radicals by chelating the copper ions. Once the hydroxyl radicals are formed by Fenton reactions, the complexes of PhAs with Cu(II) can immediately react with them, thus inhibiting the damage that they can cause to molecules of biological interest. The reactions between PhAs-Cu(II) complexes and hydroxyl free radical were estimated to be diffusion-limited (~108 M−1s−1). Thus, these chelates can reduce the harmful effects caused by the most reactive free radical existent immediately after it is formed by Fenton reactions.
Generation of Cold Magnetized Relativistic Plasmas at the Rear of Thin Foils Irradiated by Ultra-High-Intensity Laser Pulses
Authors: Korzhimanov Artem V.
Published: December 2021

A scheme to generate magnetized relativistic plasmas in a laboratory setting is proposed. It is based on the interaction of ultra-high-intensity sub-picosecond laser pulses with few-micron-thick foils or films. By means of Particle-In-Cell simulations, it is shown that energetic electrons produced by the laser and evacuated at the rear of the target trigger an expansion of the target, building up a strong azimuthal magnetic field. It is shown that in the expanding plasma sheath, a ratio of the magnetic pressure and the electron rest-mass energy density exceeds unity, whereas the plasma pressure is lower than the magnetic pressure and the electron gyroradius is lower than the plasma dimension. This scheme can be utilized to study astrophysical extreme phenomena such as relativistic magnetic reconnection in laboratory.
JSON Schemas with Semantic Annotations Supporting Data Translation
Authors: Amaro Gonçalo , Moutinho Filipe , Campos-Rebelo Rogério , Köpke Julius , Maló Pedro
Published: December 2021

As service-oriented architectures are a solution for large distributed systems, interoperability between these systems, which are often heterogeneous, can be a challenge due to the different syntax and semantics of the exchanged messages or even different data interchange formats. This paper addresses the data interchange format and data interoperability issues between XML-based and JSON-based systems. It proposes novel annotation mechanisms to add semantic annotations and complement date values to JSON Schemas, enabling an interoperability approach for JSON-based systems that, until now, was only possible for XML-based systems. A set of algorithms supporting the translation from JSON Schema to XML Schema, JSON to XML, and XML to JSON is also proposed. These algorithms were implemented in an existing prototype tool, which now supports these systems’ interoperability through semantic compatibility verification and the automatic generation of translators.
CoSiWiNeT: A Clock Synchronization Algorithm for Wide Area IIoT Network
Authors: Gore Rahul Nandkumar , Lisova Elena , Åkerberg Johan , Björkman Mats
Published: December 2021

Recent advances in the industrial internet of things (IIoT) and cyber–physical systems drive Industry 4.0 and have led to remote monitoring and control applications that require factories to be connected to remote sites over wide area networks (WAN). The adequate performance of remote applications depends on the use of a clock synchronization scheme. Packet delay variations adversely impact the clock synchronization performance. This impact is significant in WAN as it comprises wired and wireless segments belonging to public and private networks, and such heterogeneity results in inconsistent delays. Highly accurate, hardware–based time synchronization solutions, global positioning system (GPS), and precision time protocol (PTP) are not preferred in WAN due to cost, environmental effects, hardware failure modes, and reliability issues. As a software–based network time protocol (NTP) overcomes these challenges but lacks accuracy, the authors propose a software–based clock synchronization method, called CoSiWiNeT, based on the random sample consensus (RANSAC) algorithm that uses an iterative technique to estimate a correct offset from observed noisy data. To evaluate the algorithm’s performance, measurements captured in a WAN deployed within two cities were used in the simulation. The results show that the performance of the new algorithm matches well with NTP and state–of–the–art methods in good network conditions; however, it outperforms them in degrading network scenarios.
A New Low-Energy Proton Irradiation Facility to Unveil the Mechanistic Basis of the Proton-Boron Capture Therapy Approach
Authors: Ricciardi Valerio , Bláha Pavel , Buompane Raffaele , Crescente Giuseppina , Cuttone Giacomo , Gialanella Lucio , Michaličková Katarina , Pacifico Severina , Porzio Giuseppe , Manti Lorenzo
Published: December 2021

Protontherapy (PT) is a fast-growing cancer therapy modality thanks to much-improved normal tissue sparing granted by the charged particles’ inverted dose-depth profile. Protons, however, exhibit a low biological effectiveness at clinically relevant energies. To enhance PT efficacy and counteract cancer radioresistance, Proton–Boron Capture Therapy (PBCT) was recently proposed. PBCT exploits the highly DNA-damaging α-particles generated by the p + 11B→3α (pB) nuclear reaction, whose cross-section peaks for proton energies of 675 keV. Although a significant enhancement of proton biological effectiveness by PBCT has been demonstrated for high-energy proton beams, validation of the PBCT rationale using monochromatic proton beams having energy close to the reaction cross-section maximum is still lacking. To this end, we implemented a novel setup for radiobiology experiments at a 3-MV tandem accelerator; using a scattering chamber equipped with an Au foil scatterer for beam diffusion on the biological sample, uniformity in energy and fluence with uncertainties of 2% and 5%, respectively, was achieved. Human cancer cells were irradiated at this beamline for the first time with 685-keV protons. The measured enhancement in cancer cell killing due to the 11B carrier BSH was the highest among those thus far observed, thereby corroborating the mechanistic bases of PBCT.
Prevalence and Exposure to Ergonomic Risk Factors among Crop Farmers in Nigeria
Authors: Olowogbon Toyin Samuel , Babatunde Raphael Olanrewaju , Asiedu Edward , Yoder Aaron Moses
Published: December 2021

This study examined the prevalence and exposure to ergonomic risks factors among crop farmers in selected states in Nigeria. We used cross-sectional data to provide this evidence. Data were collected with the aid of a standardized questionnaire administered to farmers. A total of 480 smallholder cassava farmers selected across 24 farming communities in Kogi and Kwara states, Nigeria, were engaged in the study. Descriptive statistics and binary regression were used for analysis. About 96% of the respondents reported shoulder pain, 85% reported lower back pain, 82% reported upper back pain, 64% reported neck pain, and 53% reported elbow pain during farming operations. We found that the age of farmers (OR = 2.01) and daily duration of daily chemical spray (OR = 1.17) were risk factors, while previous training on the safe use and application of farm chemicals was found to be a protective factor (α = 0.05). The study identified affordability of farm safety measures and poor access to relevant safety information as top constraints to farmers’ adoption of safe farm practices. We concluded there is a high prevalence of ergonomic risks during cassava operations among respondents. A crop-specific co-designed ergonomic intervention targeted at Nigerian farmers to reduce exposure to ergonomic risks is recommended.