bluuebunny/crossref_metadata_2025 huggingface dataset:
Interpatient Heterogeneity in Drug Response and Protein Biomarker Expression of Recurrent Ovarian Cancer
Authors: Hoffmann Oliver Ingo , Regenauer Manuel , Czogalla Bastian , Brambs Christine , Burges Alexander , Mayer Barbara
Published: May 2022

Recurrent ovarian-cancer patients face low 5-year survival rates despite chemotherapy. A variety of guideline-recommended second-line therapies are available, but they frequently result in trial-and-error treatment. Alterations and adjustments are common in the treatment of recurrent ovarian cancer. The drug response of 30 lesions obtained from 22 relapsed ovarian cancer patients to different chemotherapeutic and molecular agents was analyzed with the patient-derived ovarian-cancer spheroid model. The profile of druggable biomarkers was immunohistochemically assessed. The second-line combination therapy of carboplatin with gemcitabine was significantly superior to the combination of carboplatin with PEGylated liposomal doxorubicin (p < 0.0001) or paclitaxel (p = 0.0007). Except for treosulfan, all nonplatinum treatments tested showed a lesser effect on tumor spheroids compared to that of platinum-based therapies. Treosulfan showed the highest efficacy of all nonplatinum agents, with significant advantage over vinorelbine (p < 0.0001) and topotecan (p < 0.0001), the next best agents. The comparative testing of a variety of treatment options in the ovarian-cancer spheroid model resulted in the identification of more effective regimens for 30% of patients compared to guideline-recommended therapies. Recurrent cancers obtained from different patients revealed profound interpatient heterogeneity in the expression pattern of druggable protein biomarkers. In contrast, different lesions obtained from the same patient revealed a similar drug response and biomarker expression profile. Biological heterogeneity observed in recurrent ovarian cancers might explain the strong differences in the clinical drug response of these patients. Preclinical drug testing and biomarker profiling in the ovarian-cancer spheroid model might help in optimizing treatment management for individual patients.
Spread Through Air Spaces (STAS) Is an Independent Prognostic Factor in Resected Lung Squamous Cell Carcinoma
Authors: Dagher Sami , Sulaiman Abdulrazzaq , Bayle-Bleuez Sophie , Tissot Claire , Grangeon-Vincent Valérie , Laville David , Fournel Pierre , Tiffet Olivier , Forest Fabien
Published: May 2022

Objective: There is no histoprognostic grading for lung squamous cell carcinoma (LUSC). Different prognostic factors have been described in the recent literature and are not always studied in parallel. Our objective was to search for morphological histopathological prognostic factors in LUSC. Materials and Methods: In this single-center retrospective study of 241 patients, all patients with LUSC who underwent surgical excision over a 12-year period were included. The primary endpoint was 5-year overall survival. Results: STAS was present in 86 (35.7%) patients. The presence of Spread Through Air Spaces (STAS) was correlated with tumor location (p < 0.001), pathological stage (p = 0.039), tumor differentiation (p = 0.029), percentage of necrosis (p = 0.004), presence of vascular and/or lymphatic emboli, budding (p = 0.02), single cell invasion (p = 0.002) and tumor nest size (p = 0.005). The percentage of tumor necrosis was correlated with the overall survival at 5 years: 44.6% of patients were alive when the percentage of necrosis was ≥50%, whereas 68.5% were alive at 5 years when the necrosis was <30% (p < 0.001). When vasculolymphatic emboli were present, the percentage of survival at 5 years was 42.5% compared to 65.5% when they were absent (p = 0.002). The presence of isolated cell invasion was correlated with a lower 5-year survival rate: 51.1% in the case of presence, versus 66% in the case of absence (p = 0.02). In univariate analysis, performance status, pathological stage pT or pN, pleural invasion, histopathological subtype, percentage of tumor necrosis, vasculolymphatic invasion, single-cell invasion, budding and tumor nest size correlated with the percentage of survival at 5 years. On multivariate analysis, only STAS > 3 alveoli (HR, 2.74; 95% CI, 1.18–6.33) was related to overall survival. Conclusion: In conclusion, extensive STAS is an independent factor of poor prognosis in LUSC. STAS is correlated with the presence of other poor prognostic factors such as emboli and pleural invasion and would reflect greater tumor aggressiveness.
The Role of Mesothelin Expression in Serous Ovarian Carcinoma: Impacts on Diagnosis, Prognosis, and Therapeutic Targets
Authors: Giordano Giovanna , Ferioli Elena , Tafuni Alessandro
Published: May 2022

Mesothelin (MSLN) is a protein expressed in the mesothelial cell lining of the pleura, peritoneum, and pericardium; its biological functions in normal cells are still unknown. Experimental studies using knockout mice have suggested that this molecule does not play an important role in development and reproduction. In contrast, it has been observed that this molecule is produced in abnormal amounts in several malignant neoplasms, such as mesotheliomas and pancreatic adenocarcinomas. Many molecular studies have also demonstrated that mesothelin is overexpressed in HSOCs. Here, we discuss the current knowledge of mesothelin and focus on its role in clinical and pathological diagnoses, as well as its impact on the prognosis of HSOC. Moreover, regarding the binding of MSLN to the ovarian cancer antigen CA125, which has been demonstrated in many studies, we also report on signal transduction pathways that may play an important role in the spread and neoplastic progression of this lethal neoplasm. Given that mesothelin is overexpressed in many solid tumours and has antigenic properties, this molecule could be considered an antigenic target for the treatment of many malignancies. Consequently, we also review the literature to report on mesothelin-targeting therapies for HSOC that have been recently investigated in many clinical studies.
Applying a Fast-Scan Cyclic Voltammetry to Explore Dopamine Dynamics in Animal Models of Neuropsychiatric Disorders
Authors: Grinevich Vladimir P. , Zakirov Amir N. , Berseneva Uliana V. , Gerasimova Elena V. , Gainetdinov Raul R. , Budygin Evgeny A.
Published: May 2022

Progress in the development of technologies for the real-time monitoring of neurotransmitter dynamics has provided researchers with effective tools for the exploration of etiology and molecular mechanisms of neuropsychiatric disorders. One of these powerful tools is fast-scan cyclic voltammetry (FSCV), a technique which has progressively been used in animal models of diverse pathological conditions associated with alterations in dopamine transmission. Indeed, for several decades FSCV studies have provided substantial insights into our understanding of the role of abnormal dopaminergic transmission in pathogenetic mechanisms of drug and alcohol addiction, Parkinson’s disease, schizophrenia, etc. Here we review the applications of FSCV to research neuropsychiatric disorders with particular attention to recent technological advances.
A Reciprocal Cross-Reactivity between Monoclonal Antibodies to SARS-CoV-2 Spike Glycoprotein S1 and Human CXCR2—An Implication of a Viral Mimic of Human CXCR2
Authors: Mizutani Tatsushi
Published: May 2022

Some viruses contain mimics of host chemokine receptors that influence host immunity; however, such viral mimics have not yet been reported for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, I focused on C-X-C motif chemokine receptor 2 (CXCR2) as a candidate chemokine receptor exploited by SARS-CoV-2. Similarities between the extracellular domain (ECD) of human CXCR2 and the SARS-CoV-2 spike glycoprotein S1 (CoV2S1) were investigated. Flow cytometric analysis of healthy donor-derived peripheral leukocytes was performed to examine the cross-reactivity between specific monoclonal antibodies against these two proteins. The results showed that CR3022, a monoclonal antibody to the receptor binding domain of CoV2S1, recognized the CXCR2 ECD, and a murine monoclonal antibody to human CXCR2 recognized recombinant CoV2S1. This reciprocal cross-reactivity suggests that CoV2S1 harbors a mimic of the CXCR2 ECD.
Survival Benefit of Tocilizumab in COVID-19 May Be Greater in Patients with Higher Measured Interleukin 6 Levels
Authors: Hall James , Salama Maha
Published: May 2022

The interleukin 6 (IL-6) receptor-blocking antibody tocilizumab was repurposed in the coronavirus pandemic with the intention of blocking the excess inflammatory activation associated with severe disease. We retrospectively evaluated the response to tocilizumab based on measured levels of IL-6 as well as other inflammatory markers. In the sample of 41 patients with measured levels, 16 received tocilizumab. In the patients who received tocilizumab, there was a statistically significant relationship between both higher IL-6 levels and measured acute phase reactants with mortality, but not in those who did not. Additionally, an improved mortality after tocilizumab was suggested with those with higher IL-6 measurements, but not in those with lower levels, but this finding failed to achieve statistical significance (p = 0.14). Though this study is limited by a small sample size and retrospective design, an association is suggested between higher IL-6 levels and improved mortality after tocilizumab.
Ecosystem Services in Southern Africa: Current and Emerging Trends—A Bibliometric Review
Authors: Nyathi Nesisa Analisa , Musakwa Walter , Delzeit Ruth , Kuhn Nikolaus J.
Published: May 2022

The assessment of ecosystem services (ESs) is important for Africa’s sustainability and progress. Healthy ecosystems benefit humans in various forms; however, continuous anthropogenic activities have led to rapid alterations in their compositions, structures and functions worldwide. Due to the lack of understanding on the role of ES assessment in southern Africa, many ES assessment practices and methodologies have been widely debated Thus, a bibliometric analysis of ESs in southern Africa was conducted for the period of 1996–2021, to present the key features of ES assessment practices and methodologies and reveal evolutionary trends in this field. The results showed that in southern Africa, not many ES assessment studies have been published; however, South Africa was the most productive country in terms of author collaboration and publication output. Other leading countries in this field include the UK, USA, Germany and Australia. The most productive institutions in southern Africa are located in South Africa, and are the University of Cape Town, the Council for Scientific and Industrial Research (CSIR), Rhodes University, the University of KwaZulu Natal, and the University of Stellenbosch. The five funding institutions that are most active in supporting ES assessment in southern Africa are European. The main publishers of the research are either American or European and include the highly influential publishers Elsevier, Wiley, MDPI, Springer Nature and Resilience Alliance. VOS Viewer was employed as a visual analysis tool and CiteSpace as a graphic analysis tool to conduct the bibliometric analysis. A key conclusion is that most authors use qualitative methods to assess people’s livelihoods and wellbeing as they relate to provisional and cultural services, while remotely sensed imagery is used as a key tool to assess the spatial extent of provisional and regulating services. Research recommendations include promoting a transdisciplinary approach in ES assessment in southern Africa.
Distribution and Environmental Impact Factors of Phytoplankton in the Bay of Bengal during Autumn
Authors: Wang Xingzhou , Sun Jun , Yu Hao
Published: May 2022

In order to better understand the effects of environmental factors and water mixing on the phytoplankton community structure in the Bay of Bengal, a field investigation was conducted from October to December 2016. A total of 276 species from 68 genera were identified, including Bacillariophyta (81 species), Miozoa (188 species), Cyanobacteria (four species), and Ochrophyta (three species). The abundance and distribution of dominant cyanobacteria gradually decreased along the latitude. This is evidenced in the vertical direction, which shows that cyanobacteria were affected by changes in environmental factors caused by the vertical mixing of seawater. The relationship between stratified N:P and phytoplankton also revealed that the changes in the vertical direction of the water deeply affected the phytoplankton community structure in the Bay of Bengal. The regions with strong vertical stratification were more favorable for the growth of cyanobacteria, while the regions with weak vertical stratification were more favorable for the growth of diatoms and dinoflagellates. According to the canonical correspondence analysis, nitrogen, silicates, phosphates, vertical stratification, and temperature were key control factors for phytoplankton communities. However, changes in these chemical parameters in the study area were also caused by the seawater cycle process.
A Systematic Review and Meta-Analysis of the Prevalence of Small Fibre Impairment in Patients with Fibromyalgia
Authors: Galosi Eleonora , Truini Andrea , Di Stefano Giulia
Published: May 2022

Converging evidence shows that patients with fibromyalgia syndrome have signs of small fibre impairment, possibly leading to pain and autonomic symptoms, with a frequency that has not yet been systematically evaluated. To fill this gap, our review aims to define the frequency of somatic and autonomic small fibre damage in patients with fibromyalgia syndrome, as assessed by objective small fibre-related testing. We found 360 articles on somatic and autonomic small fibre assessment in patients with fibromyalgia. Out of the 88 articles assessed for eligibility, 20 were included in the meta-analysis, involving 903 patients with fibromyalgia. The estimated prevalence of somatic small fibre impairment, as assessed with skin biopsy, corneal confocal microscopy, and microneurography, was 49% (95% confidence interval (CI): 39–60%, I2 = 89%), whereas the estimated prevalence of autonomic small fibre impairment, as assessed with heart rate variability, sympathetic skin response, skin conductance, and tilt testing, was 45% (95% CI: 25–65%, I2 = 91%). Our study shows that a considerable proportion of patients with fibromyalgia have somatic and autonomic small fibre impairment, as assessed by extensive small fibre-related testing. Nevertheless, the heterogeneity and inconsistencies across studies challenge the exact role of small fibre impairment in fibromyalgia symptoms.
Ready for the Road? A Socio-Technical Investigation of Fire Safety Improvement Options for Lithium-Ion Traction Batteries
Authors: Kirkels Arjan F. , Bleker Jeroen , Romijn Henny A.
Published: May 2022

Battery technology is crucial in the transition towards electric mobility. Lithium-ion batteries are conquering the market but are facing fire safety risks that might threaten further applications. In this study, we address the problem and potential solutions for traction batteries in the European Union area. We do so by taking a unique socio-technical system perspective. Therefore, a novel, mixed-method approach is applied, combining literature review; stakeholder interviews; Failure Mode, Mechanisms, and Event Analysis (FMMEA); and rapid prototyping. Our findings confirm that fire safety is an upcoming concern. Still, most stakeholders lack a full understanding of the problem. Improving safety is a shared responsibility among supply chain and societal stakeholders. For automotive applications, voluntary standard-setting on safety risks is an appropriate tool to improve fire safety, whereas for niche applications, a top-down approach setting regulations seems more suited. For both groups, the adaptation of battery pack designs to prevent thermal runaway propagation is shown to be promising from a technological, practical, and organizational perspective. The chosen mixed-method approach allowed for a holistic analysis of the problems and potential solutions. As such, it can serve as an empowerment strategy for stakeholders in the field, stimulating further discussion, agenda building, and action.
Mechanism of Cuttings Removing at the Bottom Hole by Pulsed Jet
Authors: Zhao Heqian , Shi Huaizhong , Huang Zhongwei , Chen Zhenliang , Gu Ziang , Gao Fei
Published: May 2022

Vibration drilling technology induced by hydraulic pulse can assist the bit in breaking rock at deep formation. Simultaneously, the pulsed jet generated by the hydraulic pulse promotes removal of the cuttings from the bottom hole. Nowadays, the cuttings removal mechanism of the pulsed jet is not clear, which causes cuttings to accumulate at the bottom hole and increases the risk of repeated cutting. In this paper, a pressure-flow rate fluctuation model is established to analyze the fluctuation characteristics of the pulsed jet at the bottom hole. Based on the model, the effects of displacement, well depth, drilling fluid viscosity, and flow area of the pulsed jet tool on the feature of instantaneous flow at the bottom hole are discussed. The results show that the pulsed jet causes flow rate and pressure to fluctuate at the bottom hole. When the displacement changes from 20 L/s to 40 L/s in a 2000 m well, the pulsed jet generates a flow rate fluctuation of 4–9 L/s and pressure fluctuation of 0.1–0.5 MPa at the bottom hole. With the flow area of the tool increasing from 2 cm2 to 4 cm2, the amplitude of flow rate fluctuation decreases by 72.5%, and the amplitude of pressure fluctuation decreases by more than 60%. Combined with the fluctuation feature of the flow field and the water jet attenuation law at the bottom hole, the force acting on the cuttings under the pulsed jet is derived. It is found that flow rate fluctuation improves the mechanical state of cuttings and is beneficial for cuttings tumbled off the bottom hole. This research provides theoretical guidance for pulsed jet cuttings cleaning at the bottom hole.
Switched Inductor DC–DC Boost Regulator Using Voltage-to-Time Controller for TEG Applications
Authors: Kilani Dima , Mohammad Baker , Alhawari Mohammad
Published: May 2022

This paper presents a switched inductor (SI) DC–DC boost regulator designed for thermoelectric generator (TEG) applications. To boost and regulate the output voltage, two feedback loops are implemented which control the duty cycle of the SI clock. The first loop consists of a pulse skip modulation (PSM) controller that compares the load voltage and reference voltage. Based on the comparison output, the PSM will either pass or bypass the modulated pulse width signal generated from the second loop. The second loop replaces the conventional circuit design of the pulse width modulation (PWM) with a voltage-to-time converter (VTC). The VTC converts the difference between load and supply voltage to time delay resulting in a modulated pulse width. This work is the first to report on utilizing VTC circuit in the SI boost regulator. The proposed SI boost regulator is designed using 65 nm CMOS technology which converts the TEG voltage of 50 mV to support dynamic voltage scaling in the range of 0.6 V to 0.8 V. The PSM and PWM controller loops can tune the duty cycle of the clock in the range of 0 to 70%. It achieves a peak efficiency of 60.9% at 30 μW load power. Comparing the proposed single-stage SI boost regulator with the conventional two cascaded stages of switched-inductor boost converter followed by switched capacitor regulator, the area is reduced by 9.6× and power efficiency is increased by 1.35×.
Energy and Exergy Analysis of an Ammonia Fuel Cell Integrated System for Marine Vessels
Authors: Duong Phan Anh , Ryu Borim , Kim Chongmin , Lee Jinuk , Kang Hokeun
Published: May 2022

In this paper, a new integrated system of solid oxide fuel cell (SOFC)–gas turbine (GT)–steam Rankine cycle (SRC)–exhaust gas boiler (EGB) is presented, in which ammonia is introduced as a promising fuel source to meet shipping decarbonization targets. For this purpose, an SOFC is presented as the main power-generation source for a specific marine propulsion plant; the GT and SRC provide auxiliary power for machinery and accommodation lighting, and steam from the waste heat boiler is used for heating seafarer accommodation. The combined system minimizes waste heat and converts it into useful work and power. Energy and exergy analyses are performed based on the first and second laws of thermodynamics. A parametric study of the effects of the variation in the SOFC current density, fuel utilization factor, superheat temperature, and SRC evaporation pressure is conducted to define the optimal operating parameters for the proposed system. In the present study, the energy and exergy efficiencies of the integrated system are 64.49% and 61.10%, respectively. These results serve as strong motivation for employing an EGB and SRC for waste heat recovery and increasing the overall energy-conversion efficiency of the system. The SRC energy and exergy efficiencies are 25.58% and 41.21%, respectively.
Sesquiterpene Induction by the Balsam Woolly Adelgid (Adelges piceae) in Putatively Resistant Fraser Fir (Abies fraseri)
Authors: Thomas Austin , Tilotta David C. , Frampton John , Jetton Robert M.
Published: May 2022

Fraser fir, Abies fraseri (Pursh) Poir., is a tree endemic to the Southern Appalachians and is found only in a few isolated populations at high elevations. Fraser firs are also cultivated on a commercial scale as Christmas trees. The species is imperiled by an introduced insect, the balsam woolly adelgid, Adelges piceae Ratzeburg (BWA). The insect severely damages Christmas tree crops and has caused substantial Fraser fir mortality in natural stands. Foliar terpenoids are one mechanism of host plant defense against invading insects and may be one focus of future Christmas tree breeding efforts. This study examines the correlation of foliar terpenoids with Fraser fir performance when infested with BWA. GC-MS and GC-FID analysis of artificially infested Fraser fir foliage reveals that increased concentrations of four terpenoid compounds are associated with BWA infestations. Foliar concentrations of two sesquiterpenes, camphene and humulene, are significantly higher in putatively resistant Fraser fir clones than in more susceptible clones after sustained adelgid feeding for a period of 20 weeks. Although it is unclear if the induction of these sesquiterpenes in the host fir is directly contributing to adelgid resistance, these compounds could serve as effective indicators while screening for BWA resistance in future Christmas tree breeding programs.
pH Auto-Sustain-Based Fermentation Supports Efficient Gamma-Aminobutyric Acid Production by Lactobacillus brevis CD0817
Authors: Jia Mengya , Zhu Yisong , Wang Lingqin , Sun Tianyi , Pan Hao , Li Haixing
Published: May 2022

Gamma-aminobutyric acid (GABA) plays a role in several physiological functions. GABA production by lactic acid bacteria has attracted considerable interest; however, there is need to improve production. This study aimed to develop a pH auto-sustain (PAS)-based GABA fermentation process for Lactobacillus brevis CD0817, with L-glutamic acid (solubility ~6.0 g/L and isoelectric point 3.22) as the substrate. Firstly, we determined the optimum levels of vital factors affecting GABA synthesis using Erlenmeyer flask experiments. The results showed that optimal levels of sugar, yeast extract, Tween-80, manganese ion, and temperature were 5.0 g/L, 35.0 g/L, 1.0 g/L, 16.0 mg/L, and 30.0 °C, respectively. The added L-glutamic acid (650 g per liter of medium) mostly existed in the form of solid powder was slowly released to supply the substrate and acidity essential for GABA production with the progress of fermentation. Based on the optimizations, the PAS-based GABA fermentation was performed using a 10 L fermenter. The PAS-based strategy promoted GABA synthesis by the strain of up to 321.9 ± 6.7 g/L after 48 h, with a productivity of 6.71 g/L/h and a substrate molar conversion rate of 99.6%. The findings suggest that the PAS-based fermentation is a promising method for GABA production by lactic acid bacteria.
Hyaluronidase Enhances Targeting of Hydrogel-Encapsulated Anti-CTLA-4 to Tumor Draining Lymph Nodes and Improves Anti-Tumor Efficacy
Authors: Harui Airi , Roth Michael D.
Published: May 2022

Immunotherapy targeting checkpoint inhibitors, such as CTLA-4 and/or PD-1, has emerged as a leading cancer therapy. While their combination produces superior efficacy compared to monotherapy, it also magnifies inflammatory and autoimmune toxicity that limits clinical utility. We previously reported that a peri-tumor injection of low-dose hydrogel-encapsulated anti-CTLA-4 produced anti-tumor responses that were equal to, or better than, systemic dosing despite a >80% reduction in total dose. Injection of hydrogel-encapsulated anti-CTLA-4 was associated with low serum exposure and limited autoimmune toxicity, but still synergized with anti-PD-1. In this report, we employ live and ex vivo imaging to examine whether peri-tumor administration specifically targets anti-CTLA-4 to tumor-draining lymph nodes (TDLN) and whether the incorporation of hyaluronidase enhances this effect. Tumor-free survival analysis was also used to measure the impact of hyaluronidase on tumor response. Compared to systemic dosing, peri-tumor injection of hydrogel-encapsulated anti-CTLA-4/DyLight 800 resulted in preferential labeling of TDLN. Incorporating hyaluronidase within the hydrogel improved the rapidity, intensity, and duration of TDLN labeling and significantly improved tumor-free survival. We conclude that hydrogel-encapsulated anti-CTLA acts as a localized antibody reservoir and that inclusion of hyaluronidase optimizes the blockade of CTLA-4 in TDLN and thereby imparts superior anti-tumor immunity.
Terpenoid Backbone Biosynthesis among Pig Hippocampal Pathways Impacted by Stressors
Authors: Rymut Haley E. , Rund Laurie A. , Southey Bruce R. , Johnson Rodney W. , Rodriguez-Zas Sandra L.
Published: May 2022

Neurogenomic changes induced by maternal immune activation (MIA) during gestation and the social stress of weaning can alter brain plasticity in the hippocampus of offspring. The present study furthers the understanding of how these stressors impact hippocampus gene networks. The hippocampus transcriptome was profiled in pigs that were either exposed to MIA or not and were weaned or nursed. Overall, 1576 genes were differentially expressed (FDR-adjusted p-value < 0.05 and |log2 (fold change between pig groups)| > 1.2) in response to the main and interacting effects of MIA, weaning, and sex. Functional analysis identified 17 enriched immunological and neurological pathways in the Kyoto Encyclopedia of Genes and Genomes database. The enrichment of the terpenoid backbone biosynthesis pathway was characterized by genes under-expressed in MIA relative to non-MIA exposed, males relative to females, and weaned relative to nursed pigs. On the other hand, the enrichment of drug addiction pathways was characterized by gene over-expression in MIA relative to non-exposed pigs. Our results indicate that weaning and sex can modify the effects of MIA on the offspring hippocampus. This knowledge can aid in precise identification of molecular targets to reduce the prolonged effects of pre- and postnatal stressors.
Casticin Impacts Key Signaling Pathways in Colorectal Cancer Cells Leading to Cell Death with Therapeutic Implications
Authors: Kowalski Michael , Assa Ashley , Patil Ketki , Terrell Courtney , Holliday Nathan , Pai S. Balakrishna
Published: May 2022

Colorectal cancer is the third most frequently encountered cancer worldwide. While current chemotherapeutics help to manage the disease to some extent, they have eluded achieving complete remission and are limited by their severe side effects. This warrants exploration of novel agents that are efficacious with anticipation of minimal adverse effects. In the current study, casticin, a tetramethoxyflavone, was tested for its ability to inhibit the viability of three human colorectal cancer cells: adenocarcinoma (DLD-1, Caco-2 cell lines) and human colorectal carcinoma cells (HCT116 cell line). Casticin showed potent inhibition of viability of DLD-1 and HCT116 cells. Clonogenic assay performed in DLD-1 cells revealed that casticin impeded the colony-forming efficiency of the cells, suggesting its impact on the proliferation of these cells. Further, a sustained effect of the inhibitory action upon withdrawal of the treatment was observed. Elucidation of the mechanism of action revealed that casticin impacted the extrinsic programmed cell death pathway, leading to an increase in apoptotic cells. Further, Bcl-2, the key moiety of cell survival, was affected. Notably, a significant number of cells were arrested in the G2/M phase of the cell cycle in DLD-1 cells. Due to the multifaceted action of casticin, we envision that treatment with casticin could provide an efficacious treatment option for colorectal adenocarcinomas with minimal side effects.
Age-Related Differences in Psychological Distress during the COVID-19 Pandemic
Authors: Rega Angelo , Nappo Raffaele , Simeoli Roberta , Cerasuolo Mariangela
Published: May 2022

While the negative impact of COVID-19 total lockdown on mental health in youth has been extensively studied, findings collected during subsequent waves of the pandemic, in which restrictive rules were more eased, are very sparse. Here, we explore perceived psychological distress during the partial lockdown of the third wave in Southern Italy in a large sample of students, focusing on age and gender differences. Also, we assessed whether attending the type of education could have a protective role on students’ psychological well-being. An online survey was completed by 1064 southern Italian students (age range: 8–19 years; males = 368) from March to July 2021. The survey consists of a set of questions regarding general sociodemographic information as well as several aspects of students’ psychological well-being. Psychological distress was higher in high school students compared to both elementary and middle ones. In addition, we found gender differences, but only in high school students, with females reporting higher psychological distress than males. Finally, our mediation analysis showed a mediated role of face-to-face schooling in the relationship between age and psychological distress. In conclusion, this study highlights age-related differences in psychological distress during the pandemic and the protective role of school in presence for mental health in Italian students.
Exploring Support Provided by Community Managed Organisations to Address Health Risk Behaviours Associated with Chronic Disease among People with Mental Health Conditions: A Qualitative Study with Organisational Leaders
Authors: Dray Julia , Gibson Lauren , Clinton-McHarg Tara , Byrnes Emma , Wynne Olivia , Bartlem Kate , Wilczynska Magdalena , Latter Joanna , Fehily Caitlin , Wolfenden Luke , Bowman Jenny
Published: May 2022

People living with mental health conditions experience a significantly reduced life expectancy compared to people without, largely linked to health risk behaviours and associated chronic disease. Community managed organisations (CMOs) represent an important setting in which to address health risk behaviours among people with mental health conditions. However, little is known about how these behaviours (smoking, poor nutrition, alcohol consumption, inadequate physical activity, poor sleep: SNAPS) are being addressed in this setting. One-on-one, semi-structured telephone interviews were conducted with a sample of 12 senior staff, representing 12 CMOs in New South Wales, Australia to: (1) explore types of support provided by CMOs to address the SNAPS behaviours of consumers living with a mental health condition; and (2) assess perceived organisational and staff level barriers and facilitators to providing such support. Transcribed interviews were analysed using inductive thematic analysis. This study found there was a range of supports offered by CMOs, and these differed by health risk behaviour. Findings suggest CMOs are well-placed to embed SNAPS supports as a part of their service provision; however, available funding, consistency of supports, workplace policies and culture, collaboration with other available supports, staff training and education, all impacted capacity.
Factors Associated with Symptom Burden in Adults with Chronic Kidney Disease Undergoing Hemodialysis: A Prospective Study
Authors: Gunarathne Thalwaththe Gedara Nadeeka Shayamalie , Tang Li Yoong , Lim Soo Kun , Nanayakkara Nishantha , Damayanthi Hewaratne Dassanayakege Wimala Thushari , Abdullah Khatijah L.
Published: May 2022

People with end stage renal disease and undergoing hemodialysis experience a high symptom burden that impairs quality of life. This study aimed to assess the prevalence, dynamicity and determinants of symptom burden among middle-aged and older adult hemodialysis patients. A descriptive cross-sectional study together with a longitudinal assessment was used. A total of 118 and 102 hemodialysis patients were assessed at baseline and at a 6-month follow-up. Validated questionnaires were used to assess the symptom burden, stress, illness perception and social support. Multiple linear regression analysis was used to determine the factors associated with symptom burden. The median number of symptoms experienced was 21 (Interquartile Range (IQR); 18–23) and 19 (IQR; 13–22) at baseline and 6 months, respectively. Having elevated stress (β = 0.65, p ≤ 0.005) and illness perception (β = 0.21, p = 0.02) were significantly predicted symptom burden at baseline (F (4, 112) = 55.29, p < 0.005, R2 = 0.664). Stress (β = 0.28, p = 0.003), illness perception (β = 0.2, p = 0.03), poor social support (β = −0.22, p = 0.01) and low body weight (β = −0.19, p = 0.03) were the determinants for symptom burden at 6 months (F (5, 93) = 4.85, p ≤ 0.005, R2 = 0.24). Elevated stress, illness perception level, poor social support and low post-dialysis body weight were found to be determinants for symptom burden. Attention should be given to psychosocial factors of hemodialysis patients while conducting assessment and delivering care to patients.
Assessment of the Costs Related to West Nile Virus Monitoring in Lombardy Region (Italy) between 2014 and 2018
Authors: Defilippo Francesco , Dottori Michele , Lelli Davide , Chiari Mario , Cereda Danilo , Farioli Marco , Chianese Rosa , Cerioli Monica Pierangela , Faccin Francesca , Canziani Sabrina , Trogu Tiziana , Sozzi Enrica , Moreno Ana , Lavazza Antonio , Restelli Umberto
Published: May 2022

In Italy, the West Nile Virus surveillance plan considers a multidisciplinary approach to identify the presence of the virus in the environment (entomological, ornithological, and equine surveillance) and to determine the risk of infections through potentially infected donors (blood and organ donors). The costs associated with the surveillance program for the Lombardy Region between 2014 and 2018 were estimated. The costs of the program were compared with a scenario in which the program was not implemented, requiring individual blood donation nucleic acid amplification tests (NAT) to detect the presence of WNV in human samples throughout the seasonal period of vector presence. Considering the five-year period, the application of the environmental/veterinary surveillance program allowed a reduction in costs incurred in the Lombardy Region of 7.7 million EUR. An integrated surveillance system, including birds, mosquito vectors, and dead-end hosts such as horses and humans, can prevent viral transmission to the human population, as well as anticipate the detection of WNV using NAT in blood and organ donors. The surveillance program within a One Health context has given the possibility to both document the expansion of the endemic area of WNV in northern Italy and avoid most of the NAT-related costs.
Maximal Oxygen Uptake, VO2 Max, Testing Effect on Blood Glucose Level in Adolescents with Type 1 Diabetes Mellitus
Authors: King Kristi M. , McKay Timothy , Thrasher Bradly J. , Wintergerst Kupper A.
Published: May 2022

Assessing maximal oxygen uptake (VO2 max) is generally considered safe when performed properly for most adolescents; however, for adolescents with type 1 diabetes mellitus (T1DM), monitoring glucose levels before and after exercise is critical to maintaining euglycemic ranges. Limited guidance exists for glucose level recommendations for the pediatric population; therefore, the purpose of this retrospective clinical chart review study was to determine the effects of VO2 max testing on blood glucose levels for adolescents with T1DM. A total of 22 adolescents (mean age = 15.6 ± 1.8 years; male = 13, 59.1%) with a diagnosis of T1DM participated in a Bruce protocol for VO2 max from January 2019 through February 2020. A statistically significant reduction in glucose levels between pretest (<30 min, mean = 191.1 mg/dL ± 61.2) and post-test VO2 max (<5 min, mean = 166.7 mg/dL ± 57.9); t(21) = 2.3, p < 0.05) was detected. The results from this current study can help guide health and fitness professionals in formulating glycemic management strategies in preparatory activities prior to exercise testing and during exercise testing.
Impaired Perceptions and Conspiracy Beliefs about the Way of Emergence of the COVID-19 Infection
Authors: Fenercioglu Aysen Kutan , Can Gunay , Sipahioglu Nurver Turfaner , Demir Osman , Gulluoglu Semih , Gedik Iyigun , Altintas Gul Ece , Cosgun Asena , Gurcan Zekiye
Published: May 2022

This study aimed to reveal the perceptions and conspiracy theories surrounding the new coronavirus infection. We aimed to explore associations between COVID-19 conspiracy beliefs with recommended health protective attitudes and sociodemographic features among the Turkish population. A questionnaire consisting of seven items about COVID-19 conspiracy theories and perceptions and ten items about attitudes was given to patients and their relatives in five different centres during the second national lockdown in Istanbul. A chi-square test was used to evaluate the associations of disease perceptions and conspiracy beliefs with sociodemographic features and with health protective attitudes. Logistic regression analysis was performed for significant results. Of 483 participants, 242 (50.1%) were found to have a conspiracy belief. Conspiracy theories were more frequent in the participants who were older than 50 years of age (p = 0.009) (OR: 1.83) and less frequent in higher education levels (p = 0.005) (OR: 0.499). In addition, 6.6% of the participants were infected with COVID-19, but having the infection was found to have no effect on disease perceptions or conspiracy beliefs. Wearing a mask in crowds, avoiding shaking hands and kissing, and washing hands were less frequent among conspiracy believers and participants with impaired perceptions. These results indicate that misconceptions and conspiracy beliefs are driving the adoption of disinformation about the prevention of COVID-19 infection.
The Impostor Phenomenon in the Nutrition and Dietetics Profession: An Online Cross-Sectional Survey
Authors: Landry Matthew J. , Bailey Dylan A. , Lee MinJi , Van Gundy Samuel , Ervin Audrey
Published: May 2022

The impostor phenomenon (IP) (also known as impostor syndrome) describes high-achieving individuals who, despite their objective successes, fail to internalize their accomplishments and have persistent self-doubt and fear of being exposed as a fraud or impostor. This study aimed to assess the prevalence and predictors of IP within a sample of nutrition and dietetics students and practitioners. An online cross-sectional survey was conducted and utilized a non-random, convenience sampling approach. A total of 1015 students, dietetic interns, and currently practicing and retired registered dietitian nutritionists and nutrition and dietetic technicians registered provided complete responses. IP was assessed with the Clance Impostor Phenomenon Scale (CIPS). Self-reported job satisfaction and well-being were assessed using validated scales. Average CIPS score was 66.0 ± 16.3 (range 22–99), and higher scores indicate more frequent or severe IP experiences. Frequent or intense IP was reported by 64% of survey respondents (n = 655). Older age, greater educational attainment and professional level, and membership in Academy of Nutrition and Dietetics groups were associated with lower IP scores. Greater social media use was associated with higher IP scores. Job satisfaction and overall well-being were inversely correlated with IP (p < 0.001). Findings suggest that IP experiences were common among a majority of nutrition and dietetics students and practitioners surveyed. Additional research and development of preventative strategies and interventions is needed.
Contrasting Health Effects of Bacteroidetes and Firmicutes Lies in Their Genomes: Analysis of P450s, Ferredoxins, and Secondary Metabolite Clusters
Authors: Nkosi Bridget Valeria Zinhle , Padayachee Tiara , Gront Dominik , Nelson David R. , Syed Khajamohiddin
Published: May 2022

Species belonging to the bacterial phyla Bacteroidetes and Firmicutes represent over 90% of the gastrointestinal microbiota. Changes in the ratio of these two bacterial groups were found to have contrasting health effects, including obesity and inflammatory diseases. Despite the availability of many bacterial genomes, comparative genomic studies on the gene pools of these two bacterial groups concerning cytochrome P450 monooxygenases (P450s), ferredoxins, and secondary metabolite biosynthetic gene clusters (smBGCs) are not reported. This study is aimed to address this research gap. The study revealed the presence of diverse sets of P450s, ferredoxins, and smBGCs in their genomes. Bacteroidetes species have the highest number of P450 families, ferredoxin cluster-types, and smBGCs compared to Firmicutes species. Only four P450 families, three ferredoxin cluster types, and five smBGCs are commonly shared between these two bacterial groups. Considering the above facts, we propose that the contrasting effects of these two bacterial groups on the host are partly due to the distinct nature of secondary metabolites produced by these organisms. Thus, the cause of the contrasting health effects of these two bacterial groups lies in their gene pools.
Overexpression of EgrIAA20 from Eucalyptus grandis, a Non-Canonical Aux/IAA Gene, Specifically Decouples Lignification of the Different Cell-Types in Arabidopsis Secondary Xylem
Authors: Yu Hong , Liu Mingjun , Zhu Zhangsheng , Wu Aiming , Mounet Fabien , Pesquet Edouard , Grima-Pettenati Jacqueline , Cassan-Wang Hua
Published: May 2022

Wood (secondary xylem) formation is regulated by auxin, which plays a pivotal role as an integrator of developmental and environmental cues. However, our current knowledge of auxin-signaling during wood formation is incomplete. Our previous genome-wide analysis of Aux/IAAs in Eucalyptus grandis showed the presence of the non-canonical paralog member EgrIAA20 that is preferentially expressed in cambium. We analyzed its cellular localization using a GFP fusion protein and its transcriptional activity using transactivation assays, and demonstrated its nuclear localization and strong auxin response repressor activity. In addition, we functionally tested the role of EgrIAA20 by constitutive overexpression in Arabidopsis to investigate for phenotypic changes in secondary xylem formation. Transgenic Arabidopsis plants overexpressing EgrIAA20 were smaller and displayed impaired development of secondary fibers, but not of other wood cell types. The inhibition in fiber development specifically affected their cell wall lignification. We performed yeast-two-hybrid assays to identify EgrIAA20 protein partners during wood formation in Eucalyptus, and identified EgrIAA9A, whose ortholog PtoIAA9 in poplar is also known to be involved in wood formation. Altogether, we showed that EgrIAA20 is an important auxin signaling component specifically involved in controlling the lignification of wood fibers.
Radiosensitization to γ-Ray by Functional Inhibition of APOBEC3G
Authors: Tong Ying , Kikuhara Sota , Onodera Takae , Chen Lichao , Myat Aung Bhone , Imamichi Shoji , Sasaki Yuka , Murakami Yasufumi , Nozaki Tadashige , Fujimori Hiroaki , Masutani Mitsuko
Published: May 2022

The radiosensitization of tumor cells is one of the promising approaches for enhancing radiation damage to cancer cells and limiting radiation effects on normal tissue. In this study, we performed a comprehensive screening of radiosensitization targets in human lung cancer cell line A549 using an shRNA library and identified apolipoprotein B mRNA editing enzyme catalytic subunit 3G (APOBEC3G: A3G) as a candidate target. APOBEC3G is an innate restriction factor that inhibits HIV-1 infection as a cytidine deaminase. APOBEC3G knockdown with siRNA showed an increased radiosensitivity in several cancer cell lines, including pancreatic cancer MIAPaCa2 cells and lung cancer A549 cells. Cell cycle analysis revealed that APOBEC3G knockdown increased S-phase arrest in MIAPaCa2 and G2/M arrest in A549 cells after γ-irradiation. DNA double-strand break marker γH2AX level was increased in APOBEC3G-knocked-down MIAPaCa2 cells after γ-irradiation. Using a xenograft model of A549 in mice, enhanced radiosensitivity by a combination of X-ray irradiation and APOBEC3G knockdown was observed. These results suggest that the functional inhibition of APOBEC3G sensitizes cancer cells to radiation by attenuating the activation of the DNA repair pathway, suggesting that APOBEC3G could be useful as a target for the radiosensitization of cancer therapy.
Development and Biochemical Characterization of Self-Immolative Linker Containing GnRH-III-Drug Conjugates
Authors: Schuster Sabine , Juhász Éva , Halmos Gábor , Neundorf Ines , Gennari Cesare , Mező Gábor
Published: May 2022

The human gonadotropin releasing hormone (GnRH-I) and its sea lamprey analogue GnRH-III specifically bind to GnRH receptors on cancer cells and can be used as targeting moieties for targeted tumor therapy. Considering that the selective release of drugs in cancer cells is of high relevance, we were encouraged to develop cleavable, self-immolative GnRH-III-drug conjugates which consist of a p-aminobenzyloxycarbonlyl (PABC) spacer between a cathepsin B-cleavable dipeptide (Val-Ala, Val-Cit) and the classical anticancer drugs daunorubicin (Dau) and paclitaxel (PTX). Alongside these compounds, non-cleavable GnRH-III-drug conjugates were also synthesized, and all compounds were analyzed for their antiproliferative activity. The cleavable GnRH-III bioconjugates revealed a growth inhibitory effect on GnRH receptor-expressing A2780 ovarian cancer cells, while their activity was reduced on Panc-1 pancreatic cancer cells exhibiting a lower GnRH receptor level. Moreover, the antiproliferative activity of the non-cleavable counterparts was strongly reduced. Additionally, the efficient cleavage of the Val-Ala linker and the subsequent release of the drugs could be verified by lysosomal degradation studies, while radioligand binding studies ensured that the GnRH-III-drug conjugates bound to the GnRH receptor with high affinity. Our results underline the high value of GnRH-III-based homing devices and the application of cathepsin B-cleavable linker systems for the development of small molecule drug conjugates (SMDCs).