bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative PCR for the Diagnosis of HCMV Pneumonia in HSCT Recipients and Other Immunocompromised Hosts
Authors: Berengua Carla , Martino Rodrigo
Published: March 2023

Pneumonia is among the most serious manifestations of HCMV infection, with high morbidity and mortality. Probable pneumonia is defined as the detection of HCMV in bronchoalveolar lavage (BAL) by viral isolation or DNA quantification (qPCR) combined with symptoms and/or signs of respiratory infection. However, currently, there is no reproducible and well-defined viral load (VL) from BAL that can reliably differentiate patients with pneumonia from the much more common detection of viral DNA in seropositive patients without true HCMV pneumonia. Several studies have been published with the aim of establishing an optimal VL for differentiating pneumonia from viral lung shedding. The aim of this review is to collect and analyze the methodology and the conclusions obtained in studies whose objectives included the correlation between HCMV VL in BAL and/or the plasma and the occurrence of HCMV pneumonia. For this purpose, a total of 14 articles have been included. There are some conclusions on which they all agree. PCR techniques were more sensitive and had a higher NPV than culture techniques but were less specific and had a low PPV. The mean HCMV loads in both BAL and the plasma were significantly higher in patients with pneumonitis than in those without. The HCMV load in patients with pneumonitis was higher in BAL than in the plasma, making qPCR in BAL a better predictor of HCMV pneumonitis than in the plasma. Nevertheless, this review highlights the difficulty of establishing a universal VL value, both in BAL and in the blood, to differentiate patients with HCMV pneumonia from those without. To complete the information available in these studies, prospective multicentre studies would be required. Methodologically, a large number of patients with HCMV pneumonitis would have to be included, and a subclassification of the type of immunosuppression of each patient should be made in order to obtain an optimal VL threshold in different host groups.
Bioassessment of Phylogenetic Relatedness and Plant Growth Enhancement of Endophytic Bacterial Isolates from Cowpea (Vigna unguiculata) Plant Tissues
Authors: Omomowo Olawale Israel , Babalola Olubukola Oluranti
Published: March 2023

Cowpea is of great importance to people in most tropical countries of the world. It is the preeminent indigenous African legume and a frontline option for meeting the nutritional protein demands of people and livestock. The use of an eco-friendly alternative to synthetic fertilizers and agro-pesticides has, in recent times, become an attractive research theme. Therefore, bioprospecting for effective endophytic bacteria isolates as potential bioinoculants for enhancing cowpea productivity makes this research a priority. In this study, cowpea tissues were used to isolate and characterize endophytic bacterial strains through morpho-genotypic techniques and then assessed for their in vitro growth promotion, as well as their in planta growth potential in chamber experiments. In all, 33 endophytic bacterial strains were authenticated by sequencing the 16S rRNA and through further bioinformatics analysis. Also, plant-growth promoting (PGP) genes and seed germination percentage improvements were confirmed in the endophytic bacteria isolates. The research findings highlight that the bacterial strains are molecularly diverse and some of the authenticated endophytic bacteria isolates are potential bioinoculants that can be applied in further studies to improve the agronomic productivity of cowpea plant.
COVID-19 Pandemic Control Measures and Their Impact on University Students and Family Members in a Central Region of Spain
Authors: Pérez-Pérez Lucía , Cárdaba-García Inés , Madrigal-Fernández Miguel A. , Montero-Cuadrado Federico , Sobas E. M. , Soto-Cámara Raúl
Published: March 2023

The first waves of the COVID-19 pandemic were times of great change in the lives of university students and their families in Spain. The aim of this study was to explore the psychosocial aspects and preventive measures carried out during the COVID-19 pandemic by students and family members of the nursing degree students of the University of Valladolid (Spain). The number of people surveyed was 877, by means of an ad hoc questionnaire. Relationships between variables were established by means of the Chi-square test and Student’s t-test. In addition, multivariate logistic regression was generated. The significance level used was 0.05. Students and family members maintained preventive measures= such as hand washing, correct use of masks =in closed places, avoiding crowds and maintaining social distance, but at low rates (close to 20% in all cases). Regarding psychosocial aspects, 41.07% of the participants suffered from anxiety and loneliness, while 5.2% needed to take drugs to reduce anxiety or sleep and 66.07% were dependent on technology. Suicidal behavior is related to stress, anxiety, loneliness, poor family relationships, psychotropic drug use and technology abuse. The pandemic has caused life changes in university students and their families at the psychosocial level, generating high figures of suicidal ideation regardless of age. Preventive measures adopted to control the pandemic have not been followed for the most part.
COVID-19 Pandemic Fatigue and Its Sociodemographic, Mental Health Status, and Perceived Causes: A Cross-Sectional Study Nearing the Transition to an Endemic Phase in Malaysia
Authors: Abdul Rashid Mohd Radzniwan , Syed Mohamad Sharifah Najwa , Tajjudin Ahmad Izzat Ahmad , Roslan Nuruliza , Jaffar Aida , Mohideen Fathima Begum Syed , Addnan Faizul Helmi , Baharom Nizam , Ithnin Muslimah
Published: March 2023

This study aimed to explore the socio-demographic characteristics, mental health status, and perceived causes of pandemic fatigue with COVID-19 pandemic fatigue among the general population of Malaysia. The data was collected online during the transition from the COVID-19 pandemic phase to the endemic phase in Malaysia from 1 to 30 April 2022. Sociodemographic data, Depression Anxiety Stress Scale-21 (DASS-21), perceived causes of pandemic fatigue, and the Fatigue Assessment Scale (FAS) were included in the survey. The chi-square test and a simple logistic regression analysis were used to identify predictors of pandemic fatigue. The completed survey (N = 775) included individuals aged 18 years or above [mean 31.98 (SD = 12.16)] from all states in Malaysia. Pandemic fatigue prevalence was 54.2%. Severe to extremely severe depression, anxiety, and stress symptoms were detected in 11.2%, 14.9%, and 9.1% of the participants, respectively. Younger age, non-Malay ethnicity, living alone, and higher income categories were significantly higher in the fatigued group. Higher DASS-21 scores on all domains were associated with higher FAS scores. Meanwhile, high scores for perceived tiredness from complying with the COVID-19 Standard Operating Procedure (SOP), perceived risk of infection from COVID-19, perceived hardship due to the pandemic, perceived public complacency during the pandemic, and perceived changes due to the pandemic were associated with a higher FAS score. This study provides valuable information for policymakers and mental health professionals worldwide on pandemic fatigue and its associated factors, including mental health status in Malaysia.
Predicting Low-Level Childhood Lead Exposure in Metro Atlanta Using Ensemble Machine Learning of High-Resolution Raster Cells
Authors: Frndak Seth , Yan Fengxia , Edelson Mike , Immergluck Lilly Cheng , Kordas Katarzyna , Idris Muhammed Y. , Dickinson-Copeland Carmen M.
Published: March 2023

Low-level lead exposure in children is a major public health issue. Higher-resolution spatial targeting would significantly improve county and state-wide policies and programs for lead exposure prevention that generally intervene across large geographic areas. We use stack-ensemble machine learning, including an elastic net generalized linear model, gradient-boosted machine, and deep neural network, to predict the number of children with venous blood lead levels (BLLs) ≥2 to <5 µg/dL and ≥5 µg/dL in ~1 km2 raster cells in the metro Atlanta region using a sample of 92,792 children ≤5 years old screened between 2010 and 2018. Permutation-based predictor importance and partial dependence plots were used for interpretation. Maps of predicted vs. observed values were generated to compare model performance. According to the EPA Toxic Release Inventory for air-based toxic release facility density, the percentage of the population below the poverty threshold, crime, and road network density was positively associated with the number of children with low-level lead exposure, whereas the percentage of the white population was inversely associated. While predictions generally matched observed values, cells with high counts of lead exposure were underestimated. High-resolution geographic prediction of lead-exposed children using ensemble machine learning is a promising approach to enhance lead prevention efforts.
Linguistic Predictors of Psychological Adjustment in Healthcare Workers during the COVID-19 Pandemic
Authors: Castiglioni Marco , Caldiroli Cristina Liviana , Negri Attà , Manzoni Gian Mauro , Procaccia Rossella
Published: March 2023

COVID-19 broke out in China in December 2019 and rapidly became a worldwide pandemic that demanded an extraordinary response from healthcare workers (HCWs). Studies conducted during the pandemic observed severe depression and PTSD in HCWs. Identifying early predictors of mental health disorders in this population is key to informing effective treatment and prevention. The aim of this study was to investigate the power of language-based variables to predict PTSD and depression symptoms in HCWs. One hundred thirty-five HCWs (mean age = 46.34; SD = 10.96) were randomly assigned to one of two writing conditions: expressive writing (EW n = 73) or neutral writing (NW n = 62) and completed three writing sessions. PTSD and depression symptoms were assessed both pre- and post-writing. LIWC was used to analyze linguistic markers of four trauma-related variables (cognitive elaboration, emotional elaboration, perceived threat to life, and self-immersed processing). Changes in PTSD and depression were regressed onto the linguistic markers in hierarchical multiple regression models. The EW group displayed greater changes on the psychological measures and in terms of narrative categories deployed than the NW group. Changes in PTSD symptoms were predicted by cognitive elaboration, emotional elaboration, and perceived threat to life; changes in depression symptoms were predicted by self-immersed processing and cognitive elaboration. Linguistic markers can facilitate the early identification of vulnerability to mental disorders in HCWs involved in public health emergencies. We discuss the clinical implications of these findings.
Wireless Peripheral Nerve Stimulation for The Upper Limb: A Case Report
Authors: Bellini Valentina , Baciarello Marco , Cascella Marco , Saturno Francesco , Compagnone Christian , Vittori Alessandro , Bignami Elena Giovanna
Published: March 2023

Peripheral neuro-stimulation (PNS) has been proved to be effective for the treatment of neuropathic pain as well as other painful conditions. We discuss two approaches to PNS placement in the upper extremity. The first case describes a neuropathic syndrome after the traumatic amputation of the distal phalanx of the fifth digit secondary to a work accident with lack of responsiveness to a triple conservative therapy. An upper arm region approach for the PNS was chosen. The procedure had a favorable outcome; in fact, after one month the pain symptoms were absent (VAS 0) and the pharmacological therapy was suspended. The second case presented a patient affected by progressive CRPS type II in the sensory regions of the ulnar and median nerve in the hand, unresponsive to drug therapy. For this procedure, the PNS device was implanted in the forearm. Unfortunately, in this second case the migration of the catheter affected the effectiveness of the treatment. After examining the two cases in this paper, we changed our practice and suggest the implantation of PNS for radial, median and/or ulnar nerve stimulation in the upper arm region, which has significant advantages over the forearm region.
Audit as a Tool for Improving the Quality of Stroke Care: A Review
Authors: Cappadona Irene , Corallo Francesco , Cardile Davide , Ielo Augusto , Bramanti Placido , Lo Buono Viviana , Ciurleo Rosella , D’Aleo Giangaetano , De Cola Maria Cristina
Published: March 2023

Introduction: A clinical audit is a tool that allows the evaluation of and improvement in the quality of stroke care processes. Fast, high-quality care and preventive interventions can reduce the negative impact of stroke. Objective: This review was conducted on studies investigating the effectiveness of clinical audits to improve the quality of stroke rehabilitation and stroke prevention. Method: We reviewed clinical trials involving stroke patients. Our search was performed on PubMed databases, Web of Science, and Cochrane library databases. Of the 2543 initial studies, 10 studies met the inclusion criteria. Results: Studies showed that an audit brought an improvement in rehabilitation processes when it included a team of experts, an active training phase with facilitators, and short-term feedback. In contrast, studies looking at an audit in stroke prevention showed contradictory results. Conclusions: A clinical audit highlights any deviations from clinical best practices in order to identify the causes of inefficient procedures so that changes can be implemented to improve the care system. In the rehabilitation phase, the audit is effective for improving the quality of care processes.
Rethinking Local Economic Development for Fetal Alcohol Spectrum Disorder in Renosterberg Local Municipality, South Africa
Authors: Jordan Bianca , Rashied Naiefa , Venter Marius
Published: March 2023

Two towns in Renosterberg Local Municipality (RLM) in the Northern Cape Province of South Africa, Petrusville and Philipstown, have high Fetal Alcohol Spectrum Disorder (FASD) prevalence rates. FASD is linked to poverty and imposes high national economic costs. Thus, it is critical to understand the local economic development (LED) strategies used to mitigate the high prevalence of FASD. Moreover, there is sparse literature examining adult communities where FASD children reside. Understanding these adult communities is important because FASD cannot exist without adult gestational exposure to alcohol consumption. Using a mixed-method approach, this study uses a six-phase analytic approach to investigate the drinking culture and drinking motives in RLM, applied to two cross-sectional in-depth community needs assessments, five in-depth interviews, and three focus groups. This study also evaluates how the RLM targets FASD, as well as binge and risky drinking, in its municipal economic strategy by analysing its Integrated Development Plan (IDP) with respect to an eight-stage policy development process. The results indicate that 57% of respondents expressed concern regarding the unhealthy drinking culture in RLM, 40% felt that the residents of RLM drank in response to unemployment-related hopelessness, and 52% attributed the drinking culture to a lack of hobbies and recreational opportunities. The results of an analysis of the RLM IDP through the lens of Ryder’s eight-stage policy development process suggest that the decisive policy development process is not open to the public and that, furthermore, FASD is neglected. A dedicated alcohol consumption census-style study is recommended to broadly capture alcohol consumption in RLM, allowing researchers to identify the exact alcohol consumption patterns and priority areas for the IDP and public health policy. RLM should directly publicise its policy development process so that its IDP is inclusively formulated to address FASD, risky drinking, binge drinking, and gestational alcohol consumption.
Short-Term Ambient Air Ozone Exposure and Components of Metabolic Syndrome in a Cohort of Mexican Obese Adolescents
Authors: Montes Jorge Octavio Acosta , Villarreal Albino Barraza , Piña Blanca Gladiana Beltrán , Martínez Karla Cervantes , Lugo Marlene Cortez , Romieu Isabelle , Cadena Leticia Hernández
Published: March 2023

Ambient air pollution is a major global public health concern; little evidence exists about the effects of short-term exposure to ozone on components of metabolic syndrome in young obese adolescents. The inhalation of air pollutants, such as ozone, can participate in the development of oxidative stress, systemic inflammation, insulin resistance, endothelium dysfunction, and epigenetic modification. Metabolic alterations in blood in components of metabolic syndrome (MS) and short-term ambient air ozone exposure were determined and evaluated longitudinally in a cohort of 372 adolescents aged between 9 to 19 years old. We used longitudinal mixed-effects models to evaluate the association between ozone exposure and the risk of components of metabolic syndrome and its parameters separately, adjusted using important variables. We observed statistically significant associations between exposure to ozone in tertiles in different lag days and the parameters associated with MS, especially for triglycerides (20.20 mg/dL, 95% CI: 9.5, 30.9), HDL cholesterol (−2.56 mg/dL (95% CI: −5.06, −0.05), and systolic blood pressure (1.10 mmHg, 95% CI: 0.08, 2.2). This study supports the hypothesis that short-term ambient air exposure to ozone may increase the risk of some components of MS such as triglycerides, cholesterol, and blood pressure in the obese adolescent population.
Adopting an Extended Theory of Planned Behaviour to Examine Buying Intention and Behaviour of Nutrition-Labelled Menu for Healthy Food Choices in Quick Service Restaurants: Does the Culture of Consumers Really Matter?
Authors: Sobaih Abu Elnasr E. , Algezawy Mohamed , Elshaer Ibrahim A.
Published: March 2023

This research aims to examine an extended model of the Theory of Planned Behaviour (TPB) to understand the determinants of consumers’ intentions to buy and recommend nutrition-labelled menu (NLM) items for making healthy food choices. The research examines the influence of attitude towards behaviour (ATT), subjective norms (SNs), perceived behavioural control (PBC) and health consciousness on consumers’ intentions to buy and recommend NLM. The research also examines the role of culture in shaping buying and recommendation intentions of NLM by undertaking a comparative study of the extended model among consumers in two different countries that have enough variation based on Hofstede’s cultural dimensions, i.e., the Kingdom of Saudi Arabia (KSA) and the United Kingdom (UK). The results of questionnaire surveys analysed with SmartPLS version 4 showed that ATT, SNs and health consciousness significantly predict intentions to buy NLM items among KSA consumers in quick service restaurants (QSRs). However, PBC did not have a significant influence on KSA consumers’ intentions to buy NLM items. On the other hand, ATT, PBC and health consciousness significantly predict intentions to buy NLM items among UK consumers in QSRs. Nonetheless, SNs did not have a significant influence on UK consumers’ intentions to buy NLM items. The intention to buy NLM significantly predicts the intentions to recommend NLM among consumers in both countries (KSA and UK). The results of a multi-group analysis showed significant differences between the KSA and the UK regarding the influence of both SNs and PBC on consumers’ intentions to buy NLMs as well as on their indirect influence on intentions to recommend NLM items. The results value the role of culture in shaping consumers’ intentions to buy and to recommend NLM items for healthy food choices, which has numerous implications for international QSRs, policy makers, and academics.
Physical Impact of SARS-CoV-2 Infection in a Population of Italian Healthcare Workers
Authors: Lulli Lucrezia Ginevra , Baldassarre Antonio , Chiarelli Annarita , Mariniello Antonella , Paolini Diana , Grazzini Maddalena , Mucci Nicola , Arcangeli Giulio
Published: March 2023

SARS-CoV-2 infection often causes symptoms and illness that can last for months after the acute phase, i.e., so-called “Long COVID” or Post-acute COVID-19. Due to the high prevalence of SARS-CoV-2 infection among Healthcare Workers (HCWs), post-COVID-19 symptoms can be common and threaten workers’ occupational health and healthcare systems’ functioning. The aim of this cross-sectional, observational study was to present data related to post-COVID-19 outcomes in a population of HCWs infected by COVID-19 from October 2020 to April 2021, and to identify possible factors associated with the persistence of illness, such as gender, age, previous medical conditions, and features of acute illness. A total of 318 HCWs who had become infected by COVID-19 were examined and interviewed approximately two months after their recovery from the infection. The clinical examinations were performed by Occupational Physicians in accordance with a specific protocol at the Occupational Medicine Unit of a tertiary hospital in Italy. The mean age of the participants was 45 years old, and 66.7% of the workers were women while 33.3% were men; the sample mainly consisted of nurses (44.7%). During the medical examination, more than half of the workers mentioned that they had experienced multiple residual bouts of illness after the acute phase of infection. Men and women were similarly affected. The most reported symptom was fatigue (32.1%), followed by musculoskeletal pain (13.6%) and dyspnea (13.2%). In the multivariate analysis, dyspnea (p < 0.001) and fatigue (p < 0.001) during the acute stage of illness and the presence of any limitation in working activities, in the context of fitness for a work evaluation performed while the occupational medicine surveillance program was being conducted (p = 0.025), were independently associated with any post-COVID-19 symptoms, which were considered final outcomes. The main post-COVID-19 symptoms—dyspnea, fatigue, and musculoskeletal pain—showed significant associations with dyspnea, fatigue, and musculoskeletal pain experienced during the acute stage of infection, with the presence of limitations in working activities, and pre-existing pneumological diseases. A normal weight according to body mass index was a protective factor. The identification of vulnerable workers as those with limitations in working activities, pneumological diseases, a high BMI, and of an older age and the implementation of preventive measures are key factors for preserving Occupational Health. Fitness-to-work evaluations performed by Occupational Physicians can be considered a complex index of overall health and functionality that can identify workers who may suffer from relevant post-COVID-19 symptoms.
Safety and Efficacy of Bojungikki-Tang in Advanced NSCLC Patients Receiving Treatment with Immune Checkpoint Inhibitors: Protocol for a Multicenter, Double-Blind, Randomized, Placebo-Controlled Pilot Trial
Authors: Ko Mi Mi , Jeong Mi-Kyung , Choi Chang Min , Lee Seung Hyeun , Chun Jaemoo , Yi Jin-Mu , Jang Ho , Lee Sung Yong
Published: March 2023

Cancer immunotherapy with immune checkpoint inhibitors (ICIs) is a major treatment option for several types of cancer, including non-small cell lung cancer (NSCLC). The proposed study aims to investigate the safety and efficacy of Bojungikki-tang (BJIKT) therapy (an herbal medicine) in patients with advanced NSCLC treated with ICIs. This multicenter, randomized, placebo-controlled pilot study will be performed at three academic hospitals. Thirty patients with advanced NSCLC, undergoing atezolizumab monotherapy as second- and subsequent-line treatment, will be recruited and randomly assigned to either BJIKT treatment (atezolizumab + BJIKT) or placebo (atezolizumab + placebo). The primary and secondary outcomes are the incidence of adverse events (AEs), including immune- related AEs (irAEs) and non-immune-related AEs (non-irAEs); and early termination rate, withdrawal period, symptom improvement of fatigue, and skeletal muscle loss, respectively. The exploratory outcomes are patient objective response rate and immune profile. This is an ongoing trial. Recruitment started on 25 March 2022 and is expected to be completed by 30 June 2023. This study will provide basic evidence for the safety profiles, including irAEs, of herbal medicine in patients with advanced NSCLC treated with ICIs.
Equilibrium Studies on Pd(II)–Amine Complexes with Bio-Relevant Ligands in Reference to Their Antitumor Activity
Authors: Shoukry Mohamed M. , van Eldik Rudi
Published: March 2023

This review article presents an overview of the equilibrium studies on Pd-amine complexes with bio-relevant ligands in reference to their antitumor activity. Pd(II) complexes with amines of different functional groups, were synthesized and characterized in many studies. The complex formation equilibria of Pd(amine)2+ complexes with amino acids, peptides, dicarboxylic acids and DNA constituents, were extensively investigated. Such systems may be considered as one of the models for the possible reactions occurring with antitumor drugs in biological systems. The stability of the formed complexes depends on the structural parameters of the amines and the bio-relevant ligands. The evaluated speciation curves can help to provide a pictorial presentation of the reactions in solutions of different pH values. The stability data of complexes with sulfur donor ligands compared with those of DNA constituents, can reveal information regarding the deactivation caused by sulfur donors. The formation equilibria of binuclear complexes of Pd(II) with DNA constituents was investigated to support the biological significance of this class of complexes. Most of the Pd(amine)2+ complexes investigated were studied in a low dielectric constant medium, resembling that of a biological medium. Investigations of the thermodynamic parameters reveal that the formation of the Pd(amine)2+ complex species is exothermic.
Photocatalytic Properties of ZnO:Al/MAPbI3/Fe2O3 Heterostructure: First-Principles Calculations
Authors: Al-Shami Ahmed , Sibari Anass , Mansouri Zouhir , El Kassaoui Majid , El Kenz Abdallah , Benyoussef Abdelilah , Loulidi Mohammed , Jouiad Mustapha , El Moutaouakil Amine , Mounkachi Omar
Published: March 2023

We report on theoretical investigations of a methylammonium lead halide perovskite system loaded with iron oxide and aluminum zinc oxide (ZnO:Al/MAPbI3/Fe2O3) as a potential photocatalyst. When excited with visible light, this heterostructure is demonstrated to achieve a high hydrogen production yield via a z-scheme photocatalysis mechanism. The Fe2O3: MAPbI3 heterojunction plays the role of an electron donor, favoring the hydrogen evolution reaction (HER), and the ZnO:Al compound acts as a shield against ions, preventing the surface degradation of MAPbI3 during the reaction, hence improving the charge transfer in the electrolyte. Moreover, our findings indicate that the ZnO:Al/MAPbI3 heterostructure effectively enhances electrons/holes separation and reduces their recombination, which drastically improves the photocatalytic activity. Based on our calculations, our heterostructure yields a high hydrogen production rate, estimated to be 265.05 μmol/g and 362.99 μmol/g, respectively, for a neutral pH and an acidic pH of 5. These theoretical yield values are very promising and provide interesting inputs for the development of stable halide perovskites known for their superlative photocatalytic properties.
Developmental Toxicity Studies: The Path towards Humanized 3D Stem Cell-Based Models
Authors: Branco Mariana A. , Nunes Tiago C. , Cabral Joaquim M. S. , Diogo Maria Margarida
Published: March 2023

Today, it is recognized that medicines will eventually be needed during pregnancy to help prevent to, ameliorate or treat an illness, either due to gestation-related medical conditions or pre-existing diseases. Adding to that, the rate of drug prescription to pregnant women has increased over the past few years, in accordance with the increasing trend to postpone childbirth to a later age. However, in spite of these trends, information regarding teratogenic risk in humans is often missing for most of the purchased drugs. So far, animal models have been the gold standard to obtain teratogenic data, but inter-species differences have limited the suitability of those models to predict human-specific outcomes, contributing to misidentified human teratogenicity. Therefore, the development of physiologically relevant in vitro humanized models can be the key to surpassing this limitation. In this context, this review describes the pathway towards the introduction of human pluripotent stem cell-derived models in developmental toxicity studies. Moreover, as an illustration of their relevance, a particular emphasis will be placed on those models that recapitulate two very important early developmental stages, namely gastrulation and cardiac specification.
KRAS, NRAS, BRAF, HER2 and MSI Status in a Large Consecutive Series of Colorectal Carcinomas
Authors: Martianov Aleksandr S. , Mitiushkina Natalia V. , Ershova Anastasia N. , Martynenko Darya E. , Bubnov Mikhail G. , Amankwah Priscilla , Yanus Grigory A. , Aleksakhina Svetlana N. , Tiurin Vladislav I. , Venina Aigul R. , Anuskina Aleksandra A. , Gorgul Yuliy A. , Shestakova Anna D. , Maidin Mikhail A. , Belyaev Alexey M. , Baboshkina Liliya S. , Iyevleva Aglaya G. , Imyanitov Evgeny N.
Published: March 2023

This study aimed to analyze clinical and regional factors influencing the distribution of actionable genetic alterations in a large consecutive series of colorectal carcinomas (CRCs). KRAS, NRAS and BRAF mutations, HER2 amplification and overexpression, and microsatellite instability (MSI) were tested in 8355 CRC samples. KRAS mutations were detected in 4137/8355 (49.5%) CRCs, with 3913 belonging to 10 common substitutions affecting codons 12/13/61/146, 174 being represented by 21 rare hot-spot variants, and 35 located outside the “hot” codons. KRAS Q61K substitution, which leads to the aberrant splicing of the gene, was accompanied by the second function-rescuing mutation in all 19 tumors analyzed. NRAS mutations were detected in 389/8355 (4.7%) CRCs (379 hot-spot and 10 non-hot-spot substitutions). BRAF mutations were identified in 556/8355 (6.7%) CRCs (codon 600: 510; codons 594–596: 38; codons 597–602: 8). The frequency of HER2 activation and MSI was 99/8008 (1.2%) and 432/8355 (5.2%), respectively. Some of the above events demonstrated differences in distribution according to patients’ age and gender. In contrast to other genetic alterations, BRAF mutation frequencies were subject to geographic variation, with a relatively low incidence in areas with an apparently warmer climate (83/1726 (4.8%) in Southern Russia and North Caucasus vs. 473/6629 (7.1%) in other regions of Russia, p = 0.0007). The simultaneous presence of two drug targets, BRAF mutation and MSI, was observed in 117/8355 cases (1.4%). Combined alterations of two driver genes were detected in 28/8355 (0.3%) tumors (KRAS/NRAS: 8; KRAS/BRAF: 4; KRAS/HER2: 12; NRAS/HER2: 4). This study demonstrates that a substantial portion of RAS alterations is represented by atypical mutations, KRAS Q61K substitution is always accompanied by the second gene-rescuing mutation, BRAF mutation frequency is a subject to geographical variations, and a small fraction of CRCs has simultaneous alterations in more than one driver gene.
Recent Developments in the Inhibition of Bacterial Adhesion as Promising Anti-Virulence Strategy
Authors: Pecoraro Camilla , Carbone Daniela , Parrino Barbara , Cascioferro Stella , Diana Patrizia
Published: March 2023

Infectious diseases caused by antimicrobial-resistant strains have become a serious threat to global health, with a high social and economic impact. Multi-resistant bacteria exhibit various mechanisms at both the cellular and microbial community levels. Among the different strategies proposed to fight antibiotic resistance, we reckon that the inhibition of bacterial adhesion to host surfaces represents one of the most valid approaches, since it hampers bacterial virulence without affecting cell viability. Many different structures and biomolecules involved in the adhesion of Gram-positive and Gram-negative pathogens can be considered valuable targets for the development of promising tools to enrich our arsenal against pathogens.
Integrated Bioinformatics Analysis of Shared Genes, miRNA, Biological Pathways and Their Potential Role as Therapeutic Targets in Huntington’s Disease Stages
Authors: Christodoulou Christiana C. , Papanicolaou Eleni Zamba
Published: March 2023

Huntington’s Disease (HD) is a progressive neurodegenerative disease caused by CAG repeat expansion in the huntingtin gene (HTT). The HTT gene was the first disease-associated gene mapped to a chromosome, but the pathophysiological mechanisms, genes, proteins or miRNAs involved in HD remain poorly understood. Systems bioinformatics approaches can divulge the synergistic relationships of multiple omics data and their integration, and thus provide a holistic approach to understanding diseases. The purpose of this study was to identify the differentially expressed genes (DEGs), HD-related gene targets, pathways and miRNAs in HD and, more specifically, between the pre-symptomatic and symptomatic HD stages. Three publicly available HD datasets were analysed to obtain DEGs for each HD stage from each dataset. In addition, three databases were used to obtain HD-related gene targets. The shared gene targets between the three public databases were compared, and clustering analysis was performed on the common shared genes. Enrichment analysis was performed on (i) DEGs identified for each HD stage in each dataset, (ii) gene targets from the public databases and (iii) the clustering analysis results. Furthermore, the hub genes shared between the public databases and the HD DEGs were identified, and topological network parameters were applied. Identification of HD-related miRNAs and their gene targets was obtained, and a miRNA-gene network was constructed. Enriched pathways identified for the 128 common genes revealed pathways linked to multiple neurodegeneration diseases (HD, Parkinson’s disease, Spinocerebellar ataxia), MAPK and HIF-1 signalling pathways. Eighteen HD-related hub genes were identified based on network topological analysis of MCC, degree and closeness. The highest-ranked genes were FoxO3 and CASP3, CASP3 and MAP2 were found for betweenness and eccentricity and CREBBP and PPARGC1A were identified for the clustering coefficient. The miRNA-gene network identified eleven miRNAs (mir-19a-3p, mir-34b-3p, mir-128-5p, mir-196a-5p, mir-34a-5p, mir-338-3p, mir-23a-3p and mir-214-3p) and eight genes (ITPR1, CASP3, GRIN2A, FoxO3, TGM2, CREBBP, MTHFR and PPARGC1A). Our work revealed that various biological pathways seem to be involved in HD either during the pre-symptomatic or symptomatic stages of HD. This may offer some clues for the molecular mechanisms, pathways and cellular components underlying HD and how these may act as potential therapeutic targets for HD.
A Mixture of Cervus elaphus sibiricus and Glycine max (L.) Merrill Inhibits Ovariectomy-Induced Bone Loss Via Regulation of Osteogenic Molecules in a Mouse Model
Authors: Baek Dong-Cheol , Hwang Seung-Ju , Lee Jin-Seok , Wang Jing-Hua , Son Chang-Gue , Lee Eun-Jung
Published: March 2023

Osteoporosis is a metabolic skeletal disease characterized by lowered bone mineral density and quality, which lead to an increased risk of fracture. The aim of this study was to evaluate the anti-osteoporosis effects of a mixture (called BPX) of Cervus elaphus sibiricus and Glycine max (L.) Merrill and its underlying mechanisms using an ovariectomized (OVX) mouse model. BALB/c female mice (7 weeks old) were ovariectomized. From 12 weeks of ovariectomy, mice were administered BPX (600 mg/kg) mixed in a chow diet for 20 weeks. Changes in bone mineral density (BMD) and bone volume (BV), histological findings, osteogenic markers in serum, and bone formation-related molecules were analyzed. Ovariectomy notably decreased the BMD and BV scores, while these were significantly attenuated by BPX treatment in the whole body, femur, and tibia. These anti-osteoporosis effects of BPX were supported by the histological findings for bone microstructure from H&E staining, increased activity of alkaline phosphatase (ALP), but a lowered activity of tartrate-resistant acid phosphatase (TRAP) in the femur, along with other parameters in the serum, including TRAP, calcium (Ca), osteocalcin (OC), and ALP. These pharmacological actions of BPX were explained by the regulation of key molecules in the bone morphogenetic protein (BMP) and mitogen-activated protein kinase (MAPK) pathways. The present results provide experimental evidence for the clinical relevance and pharmaceutical potential of BPX as a candidate for anti-osteoporosis treatment, especially under postmenopausal conditions.
Perioperative Tailored Treatments for Gastric Cancer: Times Are Changing
Authors: Lavacchi Daniele , Fancelli Sara , Buttitta Eleonora , Vannini Gianmarco , Guidolin Alessia , Winchler Costanza , Caliman Enrico , Vannini Agnese , Giommoni Elisa , Brugia Marco , Cianchi Fabio , Pillozzi Serena , Roviello Giandomenico , Antonuzzo Lorenzo
Published: March 2023

Resectable gastric or gastroesophageal (G/GEJ) cancer is a heterogeneous disease with no defined molecularly based treatment strategy. Unfortunately, nearly half of patients experience disease recurrence despite standard treatments (neoadjuvant and/or adjuvant chemotherapy/chemoradiotherapy and surgery). In this review, we summarize the evidence of potential tailored approaches in perioperative treatment of G/GEJ cancer, with a special focus on patients with human epidermal growth factor receptor-2(HER2)-positive and microsatellite instability-high (MSI-H) tumors. In patients with resectable MSI-H G/GEJ adenocarcinoma, the ongoing INFINITY trial introduces the concept of non-operative management for patients with complete clinical-pathological-molecular response, and this could be a novel and potential practice changing strategy. Other pathways involving vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), claudin18 isoform 2 (CLDN18.2), and DNA damage repair proteins are also described, with limited evidence until now. Although tailored therapy appears to be a promising strategy for resectable G/GEJ cancer, there are several methodological issues to address: inadequate sample size for pivotal trials, underestimation of subgroup effects, and choice of primary endpoint (tumor-centered vs. patient-centered endpoints). A better optimization of G/GEJ cancer treatment allows maximizing patient outcomes. In the perioperative phase, although caution is mandatory, times are changing and tailored strategies could introduce new treatment concepts. Overall, MSI-H G/GEJ cancer patients possess the characteristics to be the subgroup that could receive the most benefit from a tailored approach.
Changes in the Histology of Walnut (Juglans regia L.) Infected with Phomopsis capsici and Transcriptome and Metabolome Analysis
Authors: Zhou Leming , Zhu Tianhui , Han Shan , Li Shujiang , Liu Yinggao , Lin Tiantian , Qiao Tianmin
Published: March 2023

Phomopsis capsici (P. capsici) causes branch blight of walnuts, which leads to significant economic loss. The molecular mechanism behind the response of walnuts remains unknown. Paraffin sectioning and transcriptome and metabolome analyses were performed to explore the changes in tissue structure, gene expression, and metabolic processes in walnut after infection with P. capsici. We found that P. capsici caused serious damage to xylem vessels during the infestation of walnut branches, destroying the structure and function of the vessels and creating obstacles to the transport of nutrients and water to the branches. The transcriptome results showed that differentially expressed genes (DEGs) were mainly annotated in carbon metabolism and ribosomes. Further metabolome analyses verified the specific induction of carbohydrate and amino acid biosynthesis by P. capsici. Finally, association analysis was performed for DEGs and differentially expressed metabolites (DEMs), which focused on the synthesis and metabolic pathways of amino acids, carbon metabolism, and secondary metabolites and cofactors. Three significant metabolites were identified: succinic semialdehyde acid, fumaric acid, and phosphoenolpyruvic acid. In conclusion, this study provides data reference on the pathogenesis of walnut branch blight and direction for breeding walnut to enhance its disease resistance.
Combinatorial Blood Platelets-Derived circRNA and mRNA Signature for Early-Stage Lung Cancer Detection
Authors: D’Ambrosi Silvia , Giannoukakos Stavros , Antunes-Ferreira Mafalda , Pedraz-Valdunciel Carlos , Bracht Jillian W. P. , Potie Nicolas , Gimenez-Capitan Ana , Hackenberg Michael , Fernandez Hilario Alberto , Molina-Vila Miguel A. , Rosell Rafael , Würdinger Thomas , Koppers-Lalic Danijela
Published: March 2023

Despite the diversity of liquid biopsy transcriptomic repertoire, numerous studies often exploit only a single RNA type signature for diagnostic biomarker potential. This frequently results in insufficient sensitivity and specificity necessary to reach diagnostic utility. Combinatorial biomarker approaches may offer a more reliable diagnosis. Here, we investigated the synergistic contributions of circRNA and mRNA signatures derived from blood platelets as biomarkers for lung cancer detection. We developed a comprehensive bioinformatics pipeline permitting an analysis of platelet-circRNA and mRNA derived from non-cancer individuals and lung cancer patients. An optimal selected signature is then used to generate the predictive classification model using machine learning algorithm. Using an individual signature of 21 circRNA and 28 mRNA, the predictive models reached an area under the curve (AUC) of 0.88 and 0.81, respectively. Importantly, combinatorial analysis including both types of RNAs resulted in an 8-target signature (6 mRNA and 2 circRNA), enhancing the differentiation of lung cancer from controls (AUC of 0.92). Additionally, we identified five biomarkers potentially specific for early-stage detection of lung cancer. Our proof-of-concept study presents the first multi-analyte-based approach for the analysis of platelets-derived biomarkers, providing a potential combinatorial diagnostic signature for lung cancer detection.
Molecular Pathways Implicated in Radioresistance of Glioblastoma Multiforme: What Is the Role of Extracellular Vesicles?
Authors: Burko Pavel , D’Amico Giuseppa , Miltykh Ilia , Scalia Federica , Conway de Macario Everly , Macario Alberto J. L. , Giglia Giuseppe , Cappello Francesco , Caruso Bavisotto Celeste
Published: March 2023

Glioblastoma multiforme (GBM) is a primary brain tumor that is very aggressive, resistant to treatment, and characterized by a high degree of anaplasia and proliferation. Routine treatment includes ablative surgery, chemotherapy, and radiotherapy. However, GMB rapidly relapses and develops radioresistance. Here, we briefly review the mechanisms underpinning radioresistance and discuss research to stop it and install anti-tumor defenses. Factors that participate in radioresistance are varied and include stem cells, tumor heterogeneity, tumor microenvironment, hypoxia, metabolic reprogramming, the chaperone system, non-coding RNAs, DNA repair, and extracellular vesicles (EVs). We direct our attention toward EVs because they are emerging as promising candidates as diagnostic and prognostication tools and as the basis for developing nanodevices for delivering anti-cancer agents directly into the tumor mass. EVs are relatively easy to obtain and manipulate to endow them with the desired anti-cancer properties and to administer them using minimally invasive procedures. Thus, isolating EVs from a GBM patient, supplying them with the necessary anti-cancer agent and the capability of recognizing a specified tissue-cell target, and reinjecting them into the original donor appears, at this time, as a reachable objective of personalized medicine.
Editorial to the Special Issue “Homeostasis: Metals and Cellular Redox and Immunity Status”
Authors: Michalke Bernhard , Venkataramani Vivek
Published: March 2023

It is with great pleasure that we introduce this Special Issue on “Homeostasis: Metals and Cellular Redox and Immunity Status” [...]
Editorial of Special Issue “Materials for Energy Applications 2.0”
Authors: Kim Sun-Jae
Published: March 2023

Energy is a key factor in determining the growth of human society [...]
The Metabolic Features of Osteoblasts: Implications for Multiple Myeloma (MM) Bone Disease
Authors: Lungu Oxana , Toscani Denise , Burroughs-Garcia Jessica , Giuliani Nicola
Published: March 2023

The study of osteoblast (OB) metabolism has recently received increased attention due to the considerable amount of energy used during the bone remodeling process. In addition to glucose, the main nutrient for the osteoblast lineages, recent data highlight the importance of amino acid and fatty acid metabolism in providing the fuel necessary for the proper functioning of OBs. Among the amino acids, it has been reported that OBs are largely dependent on glutamine (Gln) for their differentiation and activity. In this review, we describe the main metabolic pathways governing OBs’ fate and functions, both in physiological and pathological malignant conditions. In particular, we focus on multiple myeloma (MM) bone disease, which is characterized by a severe imbalance in OB differentiation due to the presence of malignant plasma cells into the bone microenvironment. Here, we describe the most important metabolic alterations involved in the inhibition of OB formation and activity in MM patients.
Heterochronic Parabiosis Causes Dacryoadenitis in Young Lacrimal Glands
Authors: Scholand Kaitlin K. , Mack Alexis F. , Guzman Gary U. , Maniskas Michael E. , Sampige Ritu , Govindarajan Gowthaman , McCullough Louise D. , de Paiva Cintia S.
Published: March 2023

Aging is associated with inflammation and oxidative stress in the lacrimal gland (LG). We investigated if heterochronic parabiosis of mice could modulate age-related LG alterations. In both males and females, there were significant increases in total immune infiltration in isochronic aged LGs compared to that in isochronic young LGs. Male heterochronic young LGs were significantly more infiltrated compared to male isochronic young LGs. While both females and males had significant increases in inflammatory and B-cell-related transcripts in isochronic and heterochronic aged LGs compared to levels isochronic and heterochronic young LGs, females had a greater fold expression of some of these transcripts than males. Through flow cytometry, specific subsets of B cells were increased in the male heterochronic aged LGs compared to those in male isochronic aged LGs. Our results indicate that serum soluble factors from young mice were not enough to reverse inflammation and infiltrating immune cells in aged tissues and that there were specific sex-related differences in parabiosis treatment. This suggests that age-related changes in the LG microenvironment/architecture participate in perpetuating inflammation, which is not reversible by exposure to youthful systemic factors. In contrast, male young heterochronic LGs were significantly worse than their isochronic counterparts, suggesting that aged soluble factors can enhance inflammation in the young host. Therapies that aim at improving cellular health may have a stronger impact on improving inflammation and cellular inflammation in LGs than parabiosis.