bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of the Dietary Inflammatory Index to Assess the Diet of Young Physically Active Men
Authors: Kęska Anna , Pietrzak Anna , Iwańska Dagmara
Published: June 2022

Background: Chronic inflammation can lead to the development of obesity, diabetes and other chronic diseases. One of the factors causing inflammation is diet. The aim of this study was to assess the inflammatory potential of the diet, expressed by the DII index, in young physically active men. Methods: A total of 94 physically active students aged 19–23 participated in the study. The subjects’ diets were assessed on the basis of 4-day dietary records, which were then analyzed using the computer program “Diet 5.0”. The DII was calculated for each participant based on the individual consumption of the selected dietary components. The concentration of CRP protein was also determined. Results: Participants was divided into groups according to values of DII. Diets with different DIIs provided similar amounts of calories, but differed significantly in the content of many nutrients. Participants whose diets showed the most anti-inflammatory effects consumed significantly more protein, magnesium, iron, zinc, antioxidant vitamins, and B vitamins compared to others. The highest concentration of CRP protein was observed in men whose diet was described as the most pro-inflammatory (Q4 group). A significant relationship was found between DII and body fat (%) in men in the most anti-inflammatory (Q1 group) and neutral diet (Q2–Q3 group). Conclusions: The Dietary Inflammatory Index is a promising method of describing the effect of dietary intake on the risk of inflammation in young, healthy individuals engaging in regular physical activity.
The Collegiate Athlete Perspective on Return to Sport Amidst the COVID-19 Pandemic: A Qualitative Assessment of Confidence, Stress, and Coping Strategies
Authors: Levine Oscar , Terry Michael , Tjong Vehniah
Published: June 2022

(1) Background: The COVID-19 pandemic has created challenges for college athletes as they return to sport and campus life. Emerging literature highlights some of these challenges, but no studies have used a primarily qualitative approach to assess the impact of the pandemic on college athletes. The purpose of this study was to better understand factors affecting college athletes’ return to sport and campus life amidst the COVID-19 pandemic. (2) Methods: Semi-structured interviews were conducted with varsity athletes who participated in the 2020–2021 season at a single university. Qualitative analysis was performed using the Strauss and Corbin method to derive codes, categories, and themes. Additionally, Athletic Coping Skills Inventory-28 (ACSI-28) scores were recorded and analyzed using descriptive statistics. (3) Results: A total of 20 student athletes were interviewed, revealing that confidence and motivation, increased stress and anxiety, and adaptive coping strategies were common themes affecting their experiences returning to sport and campus life. Results from the ACSI-28 showed an average score of 49.5 and a range of 24–66. (4) Conclusions: Semi-structured interviews revealed factors impacting return to sport and student life. These findings can help inform how to better support college athletes throughout the remainder of the current pandemic and moving forward.
Long-Term Skin Temperature Changes after Breast Cancer Radiotherapy
Authors: Baic Agnieszka , Plaza Dominika , Lange Barbara , Michalecki Łukasz , Stanek Agata , Kowalczyk Anna , Ślosarek Krzysztof , Cholewka Armand
Published: June 2022

The aim of the study was to use thermal imaging to evaluate long-term chest temperature changes in patients who had previously been treated with radiotherapy. The examination with a thermal imaging camera involved 144 women—48 of them were patients after RT, 48 were females before breast cancer radiotherapy and the last group of participants were 48 healthy women. All patients (before and after radiotherapy) were divided into women after mastectomy and those after conservative surgery. In addition, the first group of women, those who had received radiotherapy, were divided into three other groups: up to 1 year after RT, over 1 year and up to 5 years after RT and over 5 years after RT. Due to this, it was possible to compare the results and analyse the differences between the temperature in the healthy and treated breasts. The comparison of obtained temperature results showed that the area treated by ionizing radiation is characterized by a higher temperature even a few years after the finished treatment. It is worth mentioning that despite the fact that the difference was visible on the thermograms, the patients had no observable skin lesion or change in color at the treatment site. For the results of the study provided for the group of healthy patients, there were no significant differences observed between the average temperatures in the breasts. The use of thermal imaging in the evaluation of skin temperature changes after radiotherapy showed that the average temperature in the treated breast area can change even a long time after treatment.
Global and Local Trends Affecting the Experience of US and UK Healthcare Professionals during COVID-19: Twitter Text Analysis
Authors: Slobodin Ortal , Plochotnikov Ilia , Cohen Idan-Chaim , Elyashar Aviad , Cohen Odeya , Puzis Rami
Published: June 2022

Background: Healthcare professionals (HCPs) are on the frontline of fighting the COVID-19 pandemic. Recent reports have indicated that, in addition to facing an increased risk of being infected by the virus, HCPs face an increased risk of suffering from emotional difficulties associated with the pandemic. Therefore, understanding HCPs’ experiences and emotional displays during emergencies is a critical aspect of increasing the surge capacity of communities and nations. Methods: In this study, we analyzed posts published by HCPs on Twitter to infer the content of discourse and emotions of the HCPs in the United States (US) and United Kingdom (UK), before and during the COVID-19 pandemic. The tweets of 25,207 users were analyzed using natural language processing (NLP). Results: Our results indicate that HCPs in the two countries experienced common health, social, and political issues related to the pandemic, reflected in their discussion topics, sentiments, and emotional display. However, the experiences of HCPs in the two countries are also subject to local socio-political trends, as well as cultural norms regarding emotional display. Conclusions: Our results support the potential of utilizing Twitter discourse to monitor and predict public health responses in emergencies.
Inappropriate Prescriptions in Older People—Translation and Adaptation to Portuguese of the STOPP/START Screening Tool
Authors: Monteiro Luís , Monteiro-Soares Matilde , Matos Cristiano , Ribeiro-Vaz Inês , Teixeira Andreia , Martins Carlos
Published: June 2022

Inappropriate prescribing, which encompasses the prescription of potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs), is a common problem for older people. The STOPP/START tool enables general practitioners, who are the main prescribers, to identify and reduce the incidence of PIMs and PPOs and appraise an older patient’s prescribed drugs during the diagnosis process to improve the clinical care quality. This study aimed to translate and validate the STOPP/START screening tool to enable its use by Portuguese physicians. A translation-back translation method including the validation of the obtained Portuguese version was used. Intra- and inter-rater reliability and agreement analyses were used in the validation process. A dataset containing the information of 334 patients was analyzed by one GP twice within a 2-week interval, while a dataset containing the information of 205 patients was independently analyzed by three GPs. Intra-rater reliability assessment led to a Kappa coefficient (κ) of 0.70 (0.65–0.74) for the STOPP criteria and 0.60 (0.52–0.68) for the START criteria, considered to be substantial and moderate values, respectively. The results of the inter-rater reliability rating were almost perfect for all combinations of raters (κ > 0.93). The version of the STOPP/START criteria translated into Portuguese represents an improvement in managing the medications prescribed to the elderly. It provides clinicians with a screening tool for detecting potentially inappropriate prescribing in patients older than 65 years old that is reliable and easy to use.
Association between Lifestyle Behaviours and Mental Health of Adolescents: Evidence from the Canadian HBSC Surveys, 2002–2014
Authors: Khan Asaduzzaman , Khan Shanchita R. , Lee Eun-Young
Published: June 2022

Physical activity (PA) and screen time (ST) are associated with mental health in adolescents, though little is known about their inter-relationships. This study examined the associations of PA and ST with psychosomatic complaints in adolescents. Data from four cycles of the Canadian Health Behaviour in School-aged Children (HBSC) surveys, collected between 2002 and 2014, were analysed. Eight psychosomatic health complaints were assessed and dichotomised as frequent (≥2 complaints/week) vs. infrequent. PA was assessed by number of days/week participants were physically active for ≥60 min. Discretionary ST was assessed by adding three screen uses: television, electronic games, and computer. Of the 37,829 adolescents (age 13.74 (SD 1.51) years; 52% girls), 25% boys and 39% girls reported frequent psychosomatic complaints. Multilevel logistic analyses showed that ST levels were positively associated while PA levels were negatively associated with reporting frequent psychosomatic complaints in a dose-dependent manner. Compared with ST ≤ 2 hrs/d, ST ≥ 4 hrs/d in girls and ST ≥ 6 hrs/d in boys showed higher odds of reporting psychosomatic complaints. Participating in PA ≥ 60 min every day compared to no PA showed lower odds of reporting psychosomatic complaints by 44% in girls and 57% in boys. Prospective research is needed to understand the causal pathway of these dose-dependent relationships.
Influence of Environmental Pollution and Living Conditions on Parasite Transmission among Indigenous Ecuadorians
Authors: González-Ramírez Luisa Carolina , Robalino-Flores Ximena , De la Torre Eliana , Parra-Mayorga Paúl , Prato José Gregorio , Trelis María , Fuentes Màrius Vicent
Published: June 2022

The purpose of this study was to evaluate the influence of environmental pollution and the living conditions of indigenous Ecuadorians on the transmission of enteroparasites in an Andean agricultural area located at high altitude. Environmental pollution was recorded after observation in each community. The parasites were identified by microscopic sediment analysis using physiological saline solution from macerated arthropods, washed vegetables, and human stools, utilizing four coproparasitological techniques (direct examination, Kato–Katz, ether concentration, and Ziehl–Neelsen). The results show that the inadequate disposal of human and animal excreta that contaminate soil and water, incorrect food hygiene, inadequate sanitary infrastructure in houses, a lack of animal veterinary care, and rodent proliferation are important reservoirs of zoonotic parasites. The use of excrement as fertilizer increases the number of flies, which act as mechanical vectors, and vegetables grown in areas with disperse infective parasitic forms act as vehicles that are marketed at the local, regional, and international levels. These analyses verify contamination levels of 52.7% in mechanical vectors, 70.6% in vegetables, and 98.2% in human stools. The agricultural communities analyzed maintained poor hygienic–sanitary and environmental conditions, which had a significant influence on the transmission of enteroparasites that affect human health.
From Omics to Multi-Omics Approaches for In-Depth Analysis of the Molecular Mechanisms of Prostate Cancer
Authors: Nevedomskaya Ekaterina , Haendler Bernard
Published: June 2022

Cancer arises following alterations at different cellular levels, including genetic and epigenetic modifications, transcription and translation dysregulation, as well as metabolic variations. High-throughput omics technologies that allow one to identify and quantify processes involved in these changes are now available and have been instrumental in generating a wealth of steadily increasing data from patient tumors, liquid biopsies, and from tumor models. Extensive investigation and integration of these data have led to new biological insights into the origin and development of multiple cancer types and helped to unravel the molecular networks underlying this complex pathology. The comprehensive and quantitative analysis of a molecule class in a biological sample is named omics and large-scale omics studies addressing different prostate cancer stages have been performed in recent years. Prostate tumors represent the second leading cancer type and a prevalent cause of cancer death in men worldwide. It is a very heterogenous disease so that evaluating inter- and intra-tumor differences will be essential for a precise insight into disease development and plasticity, but also for the development of personalized therapies. There is ample evidence for the key role of the androgen receptor, a steroid hormone-activated transcription factor, in driving early and late stages of the disease, and this led to the development and approval of drugs addressing diverse targets along this pathway. Early genomic and transcriptomic studies have allowed one to determine the genes involved in prostate cancer and regulated by androgen signaling or other tumor-relevant signaling pathways. More recently, they have been supplemented by epigenomic, cistromic, proteomic and metabolomic analyses, thus, increasing our knowledge on the intricate mechanisms involved, the various levels of regulation and their interplay. The comprehensive investigation of these omics approaches and their integration into multi-omics analyses have led to a much deeper understanding of the molecular pathways involved in prostate cancer progression, and in response and resistance to therapies. This brings the hope that novel vulnerabilities will be identified, that existing therapies will be more beneficial by targeting the patient population likely to respond best, and that bespoke treatments with increased efficacy will be available soon.
Formation of False Context Fear Memory Is Regulated by Hypothalamic Corticotropin-Releasing Factor in Mice
Authors: Kasama Emi , Moriya Miho , Kamimura Ryuma , Matsuki Tohru , Seki Kenjiro
Published: June 2022

Traumatic events frequently produce false fear memories. We investigated the effect of hypothalamic corticotropin-releasing factor (CRF) knockdown (Hy-Crf-KD) or overexpression (Hy-CRF-OE) on contextual fear memory, as fear stress-released CRF and hypothalamic–pituitary–adrenal axis activation affects the memory system. Mice were placed in a chamber with an electric footshock as a conditioning stimulus (CS) in Context A, then exposed to a novel chamber without CS, as Context B, at 3 h (B-3h) or 24 h (B-24h). The freezing response in B-3h was intensified in the experimental mice, compared to control mice not exposed to CS, indicating that a false fear memory was formed at 3 h. The within-group freezing level at B-24h was higher than that at B-3h, indicating that false context fear memory was enhanced at B-24h. The difference in freezing levels between B-3h and B-24h in Hy-Crf-KD mice was larger than that of controls. In Hy-CRF-OE mice, the freezing level at B-3h was higher than that of control and Hy-Crf-KD mice, while the freezing level in B-24h was similar to that in B-3h. Locomotor activity before CS and freezing level during CS were similar among the groups. Therefore, we hypothesized that Hy-Crf-KD potentiates the induction of false context fear memory, while Hy-CRF-OE enhances the onset of false fear memory formation.
Identification of Structural and Molecular Signatures Mediating Adaptive Changes in the Mouse Kidney in Response to Pregnancy
Authors: Lopez-Tello Jorge , Jimenez-Martinez Maria Angeles , Salazar-Petres Esteban , Patel Ritik , George Amy L. , Kay Richard G. , Sferruzzi-Perri Amanda N.
Published: June 2022

Pregnancy is characterized by adaptations in the function of several maternal body systems that ensure the development of the fetus whilst maintaining health of the mother. The renal system is responsible for water and electrolyte balance, as well as waste removal. Thus, it is imperative that structural and functional changes occur in the kidney during pregnancy. However, our knowledge of the precise morphological and molecular mechanisms occurring in the kidney during pregnancy is still very limited. Here, we investigated the changes occurring in the mouse kidney during pregnancy by performing an integrated analysis involving histology, gene and protein expression assays, mass spectrometry profiling and bioinformatics. Data from non-pregnant and pregnant mice were used to identify critical signalling pathways mediating changes in the maternal kidneys. We observed an expansion of renal medulla due to proliferation and infiltration of interstitial cellular constituents, as well as alterations in the activity of key cellular signalling pathways (e.g., AKT, AMPK and MAPKs) and genes involved in cell growth/metabolism (e.g., Cdc6, Foxm1 and Rb1) in the kidneys during pregnancy. We also generated plasma and urine proteomic profiles, identifying unique proteins in pregnancy. These proteins could be used to monitor and study potential mechanisms of renal adaptations during pregnancy and disease.
Carboplatin-Induced Thrombocytopenia through JAK2 Downregulation, S-Phase Cell Cycle Arrest and Apoptosis in Megakaryocytes
Authors: Wu Yi-Hong , Chen Hsing-Yu , Hong Wei-Chin , Wei Chen-Ying , Pang Jong-Hwei Su
Published: June 2022

Chemotherapy-induced thrombocytopenia (CIT) is a common complication when treating malignancies with cytotoxic agents wherein carboplatin is one of the most typical agents causing CIT. Janus kinase 2 (JAK2) is one of the critical enzymes to megakaryocyte proliferation and differentiation. However, the role of the JAK2 in CIT remains unclear. In this study, we used both carboplatin-induced CIT mice and MEG-01 cell line to examine the expression of JAK2 and signal transducer and activator of transcription 3 (STAT3) pathway. Under CIT, the expression of JAK2 was significantly reduced in vivo and in vitro. More surprisingly, the JAK2/STAT3 pathway remained inactivated even when thrombopoietin (TPO) was administered. On the other hand, carboplatin could cause prominent S phase cell cycle arrest and markedly increased apoptosis in MEG-01 cells. These results showed that the thrombopoiesis might be interfered through the downregulation of JAK2/STAT3 pathway by carboplatin in CIT, and the fact that exogenous TPO supplement cannot reactivate this pathway.
The Minus-End-Directed Kinesin OsDLK Shuttles to the Nucleus and Modulates the Expression of Cold-Box Factor 4
Authors: Xu Xiaolu , Hummel Sabine , Harter Klaus , Kolukisaoglu Üner , Riemann Michael , Nick Peter
Published: June 2022

The transition to terrestrial plants was accompanied by a progressive loss of microtubule minus-end-directed dynein motors. Instead, the minus-end-directed class-XIV kinesins expanded considerably, likely related to novel functions. One of these motors, OsDLK (Dual Localisation Kinesin from rice), decorates cortical microtubules but moves into the nucleus in response to cold stress. This analysis of loss-of-function mutants in rice indicates that OsDLK participates in cell elongation during development. Since OsDLK harbours both a nuclear localisation signal and a putative leucin zipper, we asked whether the cold-induced import of OsDLK into the nucleus might correlate with specific DNA binding. Conducting a DPI-ELISA screen with recombinant OsDLKT (lacking the motor domain), we identified the Opaque2 motif as the most promising candidate. This motif is present in the promoter of NtAvr9/Cf9, the tobacco homologue of Cold-Box Factor 4, a transcription factor involved in cold adaptation. A comparative study revealed that the cold-induced accumulation of NtAvr9/Cfp9 was specifically quelled in transgenic BY−2 cells overexpressing OsDLK-GFP. These findings are discussed as a working model, where, in response to cold stress, OsDLK partitions from cortical microtubules at the plasma membrane into the nucleus and specifically modulates the expression of genes involved in cold adaptation.
Caffeine and Chlorogenic Acid Combination Attenuate Early-Stage Chemically Induced Colon Carcinogenesis in Mice: Involvement of oncomiR miR-21a-5p
Authors: Bartolomeu Ariane Rocha , Romualdo Guilherme Ribeiro , Lisón Carmen Griñán , Besharat Zein Mersini , Corrales Juan Antonio Marchal , Chaves Maria Ángel García , Barbisan Luís Fernando
Published: June 2022

Colorectal cancer (CRC) is one of most common cancers worldwide, with high rates of mortality. Epidemiological findings demonstrate that coffee consumption reduces the risk of developing CRC by ~13%. In general, in vivo and in vitro findings demonstrate the antiproliferative, antioxidant and proapoptotic effects of brewed coffee or major bioavailable coffee compounds. Thus, it was assessed whether caffeine (CAF) and/or chlorogenic acid (CGA) attenuates the early-stage of chemically induced mouse colon carcinogenesis. Male Swiss mice were submitted to a 1,2-dimethylhydrazine/deoxycholic acid (DMH/DCA)-induced colon carcinogenesis model. These animals received CAF (50 mg/kg), CGA (25 mg/kg) or CAF+CGA (50 + 25 mg/kg) intragastrically for five times/week for ten weeks. CAF+CGA had the most pronounced effects on decreasing epithelial cell proliferation (Ki-67) and increasing apoptosis (cleaved caspase-3) in colonic crypts. This treatment also decreased the levels of proinflammatory cytokines IL-6, IL-17 and TNF-α, and downregulated the oncomiR miR-21a-5p in the colon. Accordingly, the analysis of miR-21a-5p targets demonstrated the genes involved in the negative regulation of proliferation and inflammation, and the positive regulation of apoptosis. Ultimately, CAF+CGA attenuated preneoplastic aberrant crypt foci (ACF) development. Our findings suggest that a combination of coffee compounds reduces early-stage colon carcinogenesis by the modulation of miR-21a-5p expression, highlighting the importance of coffee intake to prevent CRC.
Effect of Hypoxia-Induced Micro-RNAs Expression on Oncogenesis
Authors: Moriondo Giorgia , Scioscia Giulia , Soccio Piera , Tondo Pasquale , De Pace Cosimo Carlo , Sabato Roberto , Foschino Barbaro Maria Pia , Lacedonia Donato
Published: June 2022

MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. An aberrant regulation of gene expression by miRNAs is associated with numerous diseases, including cancer. MiRNAs expression can be influenced by various stimuli, among which hypoxia; however, the effects of different types of continuous hypoxia (moderate or marked) on miRNAs are still poorly studied. Lately, some hypoxia-inducible miRNAs (HRMs, hypoxia-regulated miRNAs) have been identified. These HRMs are often activated in different types of cancers, suggesting their role in tumorigenesis. The aim of this study was to evaluate changes in miRNAs expression both in moderate continuous hypoxia and marked continuous hypoxia to better understand the possible relationship between hypoxia, miRNAs, and colorectal cancer. We used RT-PCR to detect the miRNAs expression in colorectal cancer cell lines in conditions of moderate and marked continuous hypoxia. The expression of miRNAs was analyzed using a two-way ANOVA test to compare the differential expression of miRNAs among groups. The levels of almost all analyzed miRNAs (miR-21, miR-23b, miR-26a, miR-27b, and miR-145) were greater in moderate hypoxia versus marked hypoxia, except for miR-23b and miR-21. This study identified a series of miRNAs involved in the response to different types of continuous hypoxia (moderate and marked), highlighting that they play a role in the development of cancer. To date, there are no other studies that demonstrate how these two types of continuous hypoxia could be able to activate different molecular pathways that lead to a different expression of specific miRNAs involved in tumorigenesis.
Design and Practical Considerations for Active Polymeric Films in Food Packaging
Authors: Lai Wing-Fu , Wong Wing-Tak
Published: June 2022

Polymeric films for active food packaging have been playing an important role in food preservation due to favorable properties including high structural flexibility and high property tunability. Over the years, different polymeric active packaging films have been developed. Many of them have found real applications in food production. This article reviews, using a practical perspective, the principles of designing polymeric active packaging films. Different factors to be considered during materials selection and film generation are delineated. Practical considerations for the use of the generated polymeric films in active food packaging are also discussed. It is hoped that this article cannot only present a snapshot of latest advances in the design and optimization of polymeric active food packaging films, but insights into film development to achieve more effective active food packaging can be attained for future research.
Influence of Liposomes’ and Lipoplexes’ Physicochemical Characteristics on Their Uptake Rate and Mechanisms by the Placenta
Authors: Fliedel Louise , Alhareth Khair , Seguin Johanne , El-Khashab Marwa , Chissey Audrey , Mignet Nathalie , Fournier Thierry , Andrieux Karine
Published: June 2022

Pregnant women are still considered as drug orphans. Developing new medications for pregnancy complications is an urgent need. Nanomedicines seem to be a promising approach to control the biodistribution of drugs to ensure both the mother’s and the fetus’ safety. Understanding the interaction between nanoparticles and the placental barrier is a key factor to the success of the development of nanomedicines for pregnant women. In this study, we evaluated the behavior of fluorescent PEGylated liposomes and lipoplexes in human placental tissue using in vitro and ex vivo models, BeWo cell culture and suspended villous placental explants, respectively. Fluorescent based analytical tools such as Fluorescence activated cells sorting (FACS), confocal microscopy and HPLC coupled to fluorescence detection were used to assess liposomes penetration and their endocytosis mechanisms in the placenta. First, no influence of the PEGylation density was observed on the cellular internalization of liposomal formulations using both models. The comparison between neutral and cationic liposomes exhibits a significant higher internalization of the cationic formulation compared to the neutral ones. In addition, the HPLC quantification of the fluorescent liposomes in human villous explants demonstrated an increase of cationic liposomes uptake with increasing incubation concentrations. Similar uptake of cationic liposomes and lipoplexes, containing the same cationic lipid, the DMAPAP but with an overall neutral surface charge, was observed and evidenced the higher effect of composition than charge surface on trophoblast penetration. Moreover, both cationic liposomes and lipoplexes exhibited an endocytosis mechanism of internalization via pathways implicating dynamin. These data highlight the key role of the liposome’s lipid composition and the possibility to modulate their internalization in the placenta by adjusting their design.
Development of a Rapid Fluorescent Diagnostic System for Early Detection of the Highly Pathogenic Avian Influenza H5 Clade 2.3.4.4 Viruses in Chicken Stool
Authors: Duong Bao-Tuan , Than Duc-Duong , Ju Bae-Gum , Trinh Thuy-Tien Thi , Mok Chris-Ka Pun , Jeong Ju-Hwan , Song Min-Suk , Baek Yun-Hee , Park Hyun , Yeo Seon-Ju
Published: June 2022

Rapid diagnosis is essential for the control and prevention of H5 highly pathogenic avian influenza viruses (HPAIVs). However, highly sensitive and rapid diagnostic systems have shown limited performance due to specific antibody scarcity. In this study, two novel specific monoclonal antibodies (mAbs) for clade 2.3.4.4 H5Nx viruses were developed by using an immunogen from a reversed genetic influenza virus (RGV). These mAbs were combined with fluorescence europium nanoparticles and an optimized lysis buffer, which were further used for developing a fluorescent immunochromatographic rapid strip test (FICT) for early detection of H5Nx influenza viruses on chicken stool samples. The result indicates that the limit of detection (LoD) of the developed FICT was 40 HAU/mL for detection of HPAIV H5 clade 2.3.4.4b in spiked chicken stool samples, which corresponded to 4.78 × 104 RNA copies as obtained from real-time polymerase chain reaction (RT-PCR). An experimental challenge of chicken with H5N6 HPAIV is lethal for chicken three days post-infection (DPI). Interestingly, our FICT could detect H5N6 in stool samples at 2 DPI earlier, with 100% relative sensitivity in comparison with RT-PCR, and it showed 50% higher sensitivity than the traditional colloidal gold-based rapid diagnostic test using the same mAbs pair. In conclusion, our rapid diagnostic method can be utilized for the early detection of H5Nx 2.3.4.4 HPAIVs in avian fecal samples from poultry farms or for influenza surveillance in wild migratory birds.
Serum Proteomics in Patients with Head and Neck Cancer: Peripheral Blood Immune Response to Treatment
Authors: Astradsson Thorsteinn , Sellberg Felix , Ehrsson Ylva Tiblom , Sandström Karl , Laurell Göran
Published: June 2022

In this real-world study, the aims were to prospectively evaluate the expression of inflammatory proteins in serum collected from head and neck cancer patients before and after treatment, and to assess whether there were differences in expression associated with treatment modalities. The mixed study cohort consisted of 180 patients with head and neck cancer. The most common tumor sites were the oropharynx (n = 81), the oral cavity (n = 53), and the larynx (n = 22). Blood tests for proteomics analysis were carried out before treatment, 7 weeks after the start of treatment, and 3 and 12 months after the termination of treatment. Sera were analyzed for 83 proteins using an immuno-oncology biomarker panel (Olink, Uppsala, Sweden). Patients were divided into four treatment groups: surgery alone (Surg group, n = 24), radiotherapy with or without surgery (RT group, n = 94), radiotherapy with concomitant cisplatin (CRT group, n = 47), and radiotherapy with concomitant targeted therapy (RT Cetux group, n = 15). For the overall cohort, the expression levels of 15 of the 83 proteins changed significantly between the pretreatment sample and the sample taken 7 weeks after the start of treatment. At 7 weeks after the start of treatment, 13 proteins showed lower expression in the CRT group compared to the RT group. The majority of the inflammatory proteins had returned to their pretreatment levels after 12 months. It was clearly demonstrated that cisplatin-based chemoradiation has immunological effects in patients with head and neck cancer. This analysis draws attention to several inflammatory proteins that are of interest for further studies.
Urinary Tract Tumor Organoids Reveal Eminent Differences in Drug Sensitivities When Compared to 2-Dimensional Culture Systems
Authors: Wei Yi , Amend Bastian , Todenhöfer Tilman , Lipke Nizar , Aicher Wilhelm K. , Fend Falko , Stenzl Arnulf , Harland Niklas
Published: June 2022

Generation of organoids from urinary tract tumor samples was pioneered a few years ago. We generated organoids from two upper tract urothelial carcinomas and from one bladder cancer sample, and confirmed the expression of cytokeratins as urothelial antigens, vimentin as a mesenchymal marker, and fibroblast growth factor receptor 3 by immunohistochemistry. We investigated the dose response curves of two novel components, venetoclax versus S63845, in comparison to the clinical standard cisplatin in organoids in comparison to the corresponding two-dimensional cultures. Normal urothelial cells and tumor lines RT4 and HT1197 served as controls. We report that upper tract urothelial carcinoma cells and bladder cancer cells in two-dimensional cultures yielded clearly different sensitivities towards venetoclax, S63845, and cisplatin. Two-dimensional cultures were more sensitive at low drug concentrations, while organoids yielded higher drug efficacies at higher doses. In some two-dimensional cell viability experiments, colorimetric assays yielded different IC50 toxicity levels when compared to chemiluminescence assays. Organoids exhibited distinct sensitivities towards cisplatin and to a somewhat lesser extent towards venetoclax or S63845, respectively, and significantly different sensitivities towards the three drugs investigated when compared to the corresponding two-dimensional cultures. We conclude that organoids maintained inter-individual sensitivities towards venetoclax, S63845, and cisplatin. The preclinical models and test systems employed may bias the results of cytotoxicity studies.
miR2119, a Novel Transcriptional Regulator, Plays a Positive Role in Woody Plant Drought Tolerance by Mediating the Degradation of the CkBI-1 Gene Associated with Apoptosis
Authors: Liu Furong , Zhang Puzhi , Li Jiayang , Zhang Tianxin , Xie Lifang , Gong Chunmei
Published: June 2022

Caragana korshinskii, an important vegetation restoration species with economic and ecological benefits in the arid region of northwest China, is characterized by significant drought tolerance. However, the underlying molecular mechanisms by which miRNAs confer this trait in C. korshinskii are unclear. Here, we investigate the effect of CkmiR2119 on drought tolerance and identified its target gene, CkBI-1. A negative correlation of CkmiR2119 and CkBI-1 in both stems and leaves in a drought gradient treatment followed by target gene validation suggest that CkmiR2119 might negatively regulate CkBI-1. Consistently, a decrease in the expression of the CkBI-1 gene was observed after both transient transformation and stable transformation of CkamiR2119 in tobacco (Nicotiana tabacum). Moreover, the physiological analysis of CkamiR2119 and CkBI-1 transgenic plants further indicate that CkmiR2119 can enhance the drought tolerance of C. korshinskii in two aspects: (i) downregulating CkBI-1 expression to accelerate vessel maturation in stems; (ii) contributing to a higher level of CkBI-1 in mesophyll cells to inhibit programmed cell death (PCD). This work reveals that CkmiR2119 can increase plants’ drought tolerance by downregulating the expression of CkBI-1, providing a theoretical basis to improve plants’ ability to withstand stress tolerance by manipulating miRNAs.
Design, Synthesis, Molecular Docking Analysis and Biological Evaluations of 4-[(Quinolin-4-yl)amino]benzamide Derivatives as Novel Anti-Influenza Virus Agents
Authors: Zhang Chao , Tang Yun-Sang , Meng Chu-Ren , Xu Jing , Zhang De-Liang , Wang Jian , Huang Er-Fang , Shaw Pang-Chui , Hu Chun
Published: June 2022

In this study, a series of 4-[(quinolin-4-yl)amino]benzamide derivatives as the novel anti-influenza agents were designed and synthesized. Cytotoxicity assay, cytopathic effect assay and plaque inhibition assay were performed to evaluate the anti-influenza virus A/WSN/33 (H1N1) activity of the target compounds. The target compound G07 demonstrated significant anti-influenza virus A/WSN/33 (H1N1) activity both in cytopathic effect assay (EC50 = 11.38 ± 1.89 µM) and plaque inhibition assay (IC50 = 0.23 ± 0.15 µM). G07 also exhibited significant anti-influenza virus activities against other three different influenza virus strains A/PR/8 (H1N1), A/HK/68 (H3N2) and influenza B virus. According to the result of ribonucleoprotein reconstitution assay, G07 could interact well with ribonucleoprotein with an inhibition rate of 80.65% at 100 µM. Furthermore, G07 exhibited significant activity target PA−PB1 subunit of RNA polymerase according to the PA−PB1 inhibitory activity prediction by the best pharmacophore Hypo1. In addition, G07 was well drug-likeness based on the results of Lipinski’s rule and ADMET prediction. All the results proved that 4-[(quinolin-4-yl)amino]benzamide derivatives could generate potential candidates in discovery of anti-influenza virus agents.
User Evaluation and Metrics Analysis of a Prototype Web-Based Federated Search Engine for Art and Cultural Heritage
Authors: Pergantis Minas , Varlamis Iraklis , Giannakoulopoulos Andreas
Published: June 2022

Content and metadata concerning a specialized field such as Art and Cultural Heritage are often scattered throughout the World Wide Web, making it hard for end-users to find, especially amid the vast and often commercialized general content of the Web. This paper presents the process of designing and developing a Federated Search Engine (FSE) that collects such content from multiple credible sources of the world of Art and Culture and presents it to the user in a unified user-oriented manner, enhancing it with added functionality. The study focuses on the challenges such an endeavor presents and the technological tools, design decisions and methodology that lead to a fully functional, Web-based platform. This implemented search engine was evaluated by a group of stakeholders from the wider fields of art, culture and media during a closed test and the insights and feedback gained by these tests are herein analyzed and presented. These insights contain both the quantitative metrics of user engagement during the testing period and the qualitative information presented by the stakeholders through interviews. The above findings are thoroughly discussed and lead to conclusions regarding the usefulness and viability of Web applications in the aggregation and diffusion of Art and Cultural Heritage related content.
Evaluation of the Appropriate Use of Coronary Computed Tomography Angiography: A Retrospective, Single-Center Analysis
Authors: Birkl Katharina , Beyer Christoph , Plank Fabian , Feuchtner Gudrun Maria , Friedrich Guy
Published: June 2022

Purpose: We assessed the application of appropriate use criteria of coronary computed tomography angiography (CCTA) in comparison to invasive coronary angiography results and revascularization rates in patients with coronary artery disease (CAD). Methods: 1305 patients referred to invasive coronary angiography (ICA) after CCTA were evaluated retrospectively. The primary indication for CCTA was assessed according to the consensus for intermediate-risk (15–85% pre-test probability) into appropriate (A), inappropriate (I), and uncertain while referring to published guidelines. Patients’ risk factors, angina, and heart failure symptoms (Canadian Cardiovascular Society classification (CCSC), New York Heart Association (NYHA); clinical data; and ICA results were gathered. Results: Of 1305 patients referred to CCTA prior to ICA, 496 (38.0%) were appropriate, 766 (56.9%) inappropriate, and 43 (3.3%) uncertain. Of 766 patients with inappropriate CCTA referrals, 370 (48.3%) were classified as “inappropriately low” (<15% pre-test probability) and 396 (51.7%) as “inappropriately high” (>85%) in regard to the recommended CCTA utilization. Sub-analysis of the adherence to the appropriate use criteria did not differ between the source of the referring physicians (intramural tertiary, private practice primary care, or external secondary care hospitals). Obstructive CAD with subsequent revascularization rates (total of 39.2%) did not differ significantly between the appropriate (38.3%), inappropriate (41.0%), or uncertain (23.3%) groups (p = 0.068). Conclusion: The total coronary revascularization rate after CCTA was 39.2% and not different among low, intermediate, and pre-test probability groups. These findings support the role of CCTA as an excellent gatekeeper in patients with suspected obstructive CAD even beyond pre-test probability calculation models.
A Prospective Cross-Sectional Study on the Comparison of Ultrasound Assessment vs. Palpation in Chronic Lymphocytic Leukemia Patients in the Era of Targeted Therapy
Authors: Benedetti Edoardo , Mavilia Fabrizio , Baratè Claudia , Bramanti Emilia , Morganti Riccardo , Cervetti Giulia , Capochiani Enrico , Bruno Benedetto , Pelosini Matteo , Stella Salvatore Massimo , Galimberti Sara
Published: June 2022

Background. In IWCLL guidelines, progressive splenomegaly and lymphadenopathy are signs of active disease. In this study, we have tested the hypotheses if US could be a reliable tool for both superficial lymphnodes (SupLNs) and splenic assessment in chronic lymphocytic leukemia (CLL) patients. Methods. We enrolled N = 75 patients. SupLN and the spleen were assessed by two independent physicians (M1 and M2) by palpation and by a third physician (M3) with ultrasound sonography (US) using two different sonographers (US1 and US2). The results of M1 vs. M2 assessment, US1 vs. US2, palpation vs. US were compared. The echostructure of N = 1037 SupLN and of the spleen was also investigated. Results. The dimensions of SupLNs assessed by MD1 vs. MD2 were statistically discordant. Splenic size was concordant. There was concordance between US1 and US2 SupLN and splenic assessment. US found a higher number of pathological SupLN (Cohen’s Kappa < 0.1) than palpation, which misses remarkable-sized SupLNs. LN echostructure and splenic involvement patterns were described. Conclusions. US is a reliable, radiation-free tool useful in clinical practice to assess SupLN and splenic involvement in CLL.
Five Years of Direct Oral Anticoagulants Use in Italy: Adverse Drug Reactions from the Italian National Pharmacovigilance Network
Authors: Lavalle Carlo , Mariani Marco Valerio , Piro Agostino , Magnocavallo Michele , Vetta Giampaolo , Trivigno Sara , Forleo Giovanni Battista , Della Rocca Domenico Giovanni , Uguccioni Massimo , Russo Vincenzo , Summaria Francesco , Di Lullo Luca
Published: June 2022

Background: Direct oral anticoagulants (DOACs) are the preferred anticoagulant drugs for the prevention of atrial fibrillation (AF)-related thromboembolic complications and for the treatment and the prevention of recurrences of venous thromboembolism (VTE). The evaluation of self-reported adverse drug reactions (ADRs) available from databases of drug-regulatory agencies such as the Italian Medicines Agency (AIFA) pharmacovigilance database represents a novel aid to guide decision making. Objective: To assess the safety profile of DOACs by analyzing ADR rates in the real-world Italian scenario. Methods: Post-marketing surveillance data recorded by the National Pharmacovigilance Network were retrieved for the time period 2017–2021 from the AIFA online site. The following data were collected for each DOAC: total ADR number, serious ADR number, gastrointestinal (GI) ADR, intracranial hemorrhage events (ICH ADR), and more frequently reported ADR for the study year. The safety profile was expressed by the risk index (RI). Results: Rivaroxaban use was associated with consistent and stable low rates of serious ADR, GI ADR, and ICH ADR across the 5-year study period. Rivaroxaban and apixaban showed the lowest RI for serious ADR and GI ADR, while rivaroxaban use was associated with significantly lower ICH events as compared to apixaban. Dabigatran was related to the highest RIs for every ADR class, in particular GI ADRs. Conclusions: DOACs presented an acceptable safety profile in the current post-market analysis. However, rivaroxaban and apixaban were associated with more favorable safety profiles as compared to dabigatran, while rivaroxaban provoked statistically significantly fewer ICH events as compared to apixaban.
New Generation Pulse Modulation in Holmium:YAG Lasers: A Systematic Review of the Literature and Meta-Analysis
Authors: Sánchez-Puy Antoni , Bravo-Balado Alejandra , Diana Pietro , Baboudjian Michael , Piana Alberto , Girón Irene , Kanashiro Andrés K. , Angerri Oriol , Contreras Pablo , Eisner Brian H. , Balañà Josep , Sánchez-Martín Francisco M. , Millán Félix , Palou Joan , Emiliani Esteban
Published: June 2022

(1) Background: New pulse modulation (PM) technologies in Holmium:YAG lasers are available for urinary stone treatment, but little is known about them. We aim to systematically evaluate the published evidence in terms of their lithotripsy performance. (2) Methods: A systematic electronic search was performed (MEDLINE, Scopus, and Cochrane databases). We included all relevant publications, including randomized controlled trials, non-randomized comparative and non-comparative studies, and in-vitro studies investigating Holmium:YAG lithotripsy performance employing any new PM. (3) Results: Initial search yielded 203 studies; 24 studies were included after selection: 15 in-vitro, 9 in-vivo. 10 In-vitro compared Moses with regular PM, 1 compared Quanta’s, 1 Dornier MedTech’s, 2 Moses with super Thulium Fiber Laser, and 1 compared Moses with Quanta PMs. Six out of seven comparative studies found a statistically significant difference in favor of new-generation PM technologies in terms of operative time and five out of six in fragmentation time; two studies evaluated retropulsion, both in favor of new-generation PM. There were no statistically significant differences regarding stone-free rate, lasing and operative time, and complications between Moses and regular PM when data were meta-analyzed. (4) Conclusions: Moses PM seems to have better lithotripsy performance than regular modes in in-vitro studies, but there are still some doubts about its in-vivo results. Little is known about the other PMs. Although some results favor Quanta PMs, further studies are needed.
Psychological Interventions in a Pandemic Emergency: A Systematic Review and Meta-Analysis of SARS-CoV-2 Studies
Authors: D’Onofrio Grazia , Trotta Nicoletta , Severo Melania , Iuso Salvatore , Ciccone Filomena , Prencipe Anna Maria , Nabavi Seyed Mohammad , De Vincentis Gabriella , Petito Annamaria
Published: June 2022

Background: The study aim was to review the evidence and effectiveness of psychological interventions applied during Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. Methods: A literature search was run from April 2020 to April 2021. The inclusion criteria were: (1) RCTs or observational studies; (2) professional health carers and patients who had contracted coronavirus during the pandemic; (3) adults and elderly people with a viral infection diagnosis; (4) suitable measures to assess intervention effectiveness on clinical status and psychological and behavioral aspects. An internal validity assessment was planned using robvis. Data were synthesized according to PICO criteria. Results: A total of 12 studies were selected. Studies measuring mental health outcomes demonstrated the greatest reduction in symptoms, with eight out of the twelve studies demonstrating a reduction in symptoms that reached statistical significance (p < 0.05) and four of the studies reaching a higher significance level of p < 0.01. The type of psychological intervention was predominantly cognitive behavioral therapy (CBT). All studies except one was run online. Conclusion: Psychological interventions have a benefit on mental health outcomes, even if performed online. In particular, CBT seems to be the psychological intervention that is used more and also seems to have a larger effect size on the mitigation of mental health symptoms and increasing resilience.